Stress

STRESS

(Asthma, Biomedical Indicators, Biophysical Indicators, Depression, Heart Disease, Hypertension, Immunological Indicators)

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January 2003

6264. Roder I, Boekaerts M, Kroonenberg PM. The stress and coping questionnaire for children (school version and asthma version): construction, factor structure, and psychometric properties. Psychol Rep. 2002 Aug;91(1):29-36.

Based on Lazarus and Folkman's 1984 Stress-Coping Model, a self-report measure for children between 8 and 12 years of age was constructed. It is called the Stress and Coping Questionnaire for Children (School version and Asthma version) and measures children's emotional responses and coping strategies when they confront school-related and asthma-related stressors. The factor structure of this questionnaire was assessed and cross-validated in two samples, one of 392 primary school children without a chronic disease and one of 119 children with asthma. Five scales of coping strategies with regard to two school-related stressors and one asthma-related stressor were distinguished in a reliable way, Approach, Avoidance, Seeking Social Support, Aggression, and Crying.

6265. Singh N; Abbas SS; Singh V; Singh Adaptogens - anti stress agents a study focusing Indian plants Antiseptic. 2002 Jul; 99(7): 243-9. No abstract.

6266. Singh N; Syed Sadiq A; Singh V; Singh. Adaptogens anti stress agents a study focusing Indian plants Antiseptic. 2002 Jun; 99(6): 198-201

ABSTRACT: This article has been presented with a view to acquaint the readers about plant adaptogens/ antistress agent. Although relation of stress has been recognized in genesis of diseases long back, a scientific database is still missing. The pharmaco-clinical studies carried out in this regard are a new venture in Stress-Pharmacology. It is meant to provide new research awareness in the field regarding the fact about stress, Stress-disease and their prevention and treatment. This is more important in view of the fact that there are no drugs for such stress-related diseases in the armamentarium of modern drug therapy. Simple animal models like swimming endurance, immobilization induced gastric ulcers, adrenal function during stress, CCI4 hepatotoxicity, anoxia tolerance test, brain neurotransmitters and enzyme and CNS receptors levels of neurohumorals after swimming immobilization and gravitational stress, milk induced leucocytosis, lipid peroxidase assessment for prevention of cell damage through anti-oxidant activity were carried out to evaluate the adaptogenic activity of these plants in rats and mice. Clinical trial in diseases related to stress like bronchial asthma, hypertension, cellular immunity, viral encephalitis, chronic fatigue syndrome were carried out in man.

6267. Wamboldt FS, Ho J, Milgrom H, Wamboldt MZ, Sanders B, Szefler SJ, Bender BG. Prevalence and correlates of household exposures to tobacco smoke and pets in children with asthma. J Pediatr. 2002 Jul;141(1):109-15.

OBJECTIVES: To examine the prevalence rates of household smoking and ownership of a furred or feathered pet, the intercorrelation of these home environment measures, and their association with sociodemographic, family, and child asthma variables. STUDY DESIGN: Children with asthma (n = 152, aged 7-18 years) with asthma and their primary parent were evaluated through the use of reliable and valid questionnaires focusing on exposure to household smoke and furred or feathered pets as well as sociodemographic, family, and asthma variables. RESULTS: Prevalence of household smoking and pet ownership were high and comparable to normal levels in the US population. Smoking and pet ownership were not correlated with each other or with asthma medication adherence. Sociodemographic, family, and asthma variables showed distinct patterns of correlation with smoking and pet status. Household smoking was associated with poorer family resources and greater stress; pet ownership was associated with greater resources. CONCLUSIONS: Smoke exposure and pet ownership are not related to one another in children with asthma and will require independent counseling strategies because they relate in different and opposite ways to socioeconomic status.

6268. Weisberg RB, Bruce SE, Machan JT, Kessler RC, Culpepper L, Keller MB. Nonpsychiatric illness among primary care patients with trauma histories and posttraumatic stress disorder. Psychiatr Serv. 2002 Jul;53(7):848-54.

OBJECTIVE: The authors examined the relationship between posttraumatic stress disorder (PTSD), trauma, and self-reported nonpsychiatric medical conditions in a sample of 502 primary care patients with one or more anxiety disorders. METHODS: Primary care patients with one or more DSM-IV anxiety disorders were assessed for comorbid psychiatric and substance use problems and for a history of trauma. These individuals also completed a self-report measure of current and lifetime medical conditions, lifetime tobacco use, and current regular exercise. RESULTS: Of 502 participants with at least one anxiety disorder, 84 (17 percent) reported no history of trauma, 233 (46 percent) had a history of trauma but no PTSD, and 185 (37 percent) met DSM-IV criteria for PTSD. Patients with PTSD reported a significantly greater number of current and lifetime medical conditions than did participants with other anxiety disorders but without PTSD. Primary care patients with PTSD were more likely to have had a number of specific medical problems, including anemia, arthritis, asthma, back pain, diabetes, eczema, kidney disease, lung disease, and ulcer. Possible explanations for the greater rates of medical conditions among participants with PTSD were examined as predictors in multiple regression. PTSD was found to be a stronger predictor of reported number of medical problems than trauma history, physical injury, lifestyle factors, or comorbid depression. CONCLUSIONS: These findings suggest that PTSD is associated with a higher rate of general medical complaints.

Biochemical Indicators:

6269. Hoeldtke RD, Bryner KD, McNeill DR, Hobbs GR, Riggs JE, Warehime SS, Christie I, Ganser G, Van Dyke K. Nitrosative stress, uric Acid, and peripheral nerve function in early type 1 diabetes. Diabetes 2002 Sep;51(9):2817-25

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO(x)) were 34.0 +/- 4.9 micro mol/l in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine (NTY) was 13.3 +/- 2.0 micro mol/l in the control subjects and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 in the diabetic patients (P <0.01). Uric acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor nerve conduction velocity for the median, ulnar, and peroneal nerves was decreased in patients with high versus low NTY (mean Z score -0.522 +/- 0.25 versus 0.273 +/- 0.22; P < 0.025). Patients with high NO(x) had decreased sweating, and those with suppressed uric acid had decreased autonomic function. In conclusion, nitrosative stress in early diabetes is associated with suppressed uric acid and deterioration in peripheral nerve function.

6270. Hughes MF. Arsenic toxicity and potential mechanisms of action. Toxicol Lett 2002 Jul 7;133(1):1-16

Exposure to the metalloid arsenic is a daily occurrence because of its environmental pervasiveness. Arsenic, which is found in several different chemical forms and oxidation states, causes acute and chronic adverse health effects, including cancer. The metabolism of arsenic has an important role in its toxicity. The metabolism involves reduction to a trivalent state and oxidative methylation to a pentavalent state. The trivalent arsenicals, including those methylated, have more potent toxic properties than the pentavalent arsenicals. The exact mechanism of the action of arsenic is not known, but several hypotheses have been proposed. At a biochemical level, inorganic arsenic in the pentavalent state may replace phosphate in several reactions. In the trivalent state, inorganic and organic (methylated) arsenic may react with critical thiols in proteins and inhibit their activity. Regarding cancer, potential mechanisms include genotoxicity, altered DNA methylation, oxidative stress, altered cell proliferation, co-carcinogenesis, and tumor promotion. A better understanding of the mechanism(s) of action of arsenic will make a more confident determination of the risks associated with exposure to this chemical.

Depression:

6271. Armenian HK, Morikawa M, Melkonian AK, Hovanesian A, Akiskal K, Akiskal HS. Risk factors for depression in the survivors of the 1988 earthquake in Armenia. J Urban Health. 2002 Sep;79(3):373-82.

Most studies of psychopathology following disasters are concerned with posttraumatic stress disorder (PTSD). The present analyses sought to assess the rate and determinants of depression in adult survivors of the 1988 earthquake in Armenia. Unlike previous studies of earthquakes, the present analyses derive from a well-defined cohort of survivors who underwent diagnostic interviewing to characterize psychiatric morbidity. As part of a cohort study of 32,743 survivors of the 1988 earthquake in Armenia, a stratified population sample of 1,785 persons was interviewed about 2 years following the disaster using a special questionnaire based on the National Institute of Mental Health (NIMH) Disaster Interview Schedule/Disaster Supplement. 52% met the criteria for major depression. Of these, a total of 177 cases of depression with no other psychiatric diagnosis or comorbidity were compared with 583 controls from the same interviewed group who did not fulfill the criteria for any psychiatric disorder. Cases and controls were compared as to data obtained independently at the aftermath of the disaster on a number of exposures and characteristics related to the earthquake. More of the cases involved females (odds ratio [OR] for males 0.7 [95% confidence interval [CI] 0.5-0.9]) and from the city of Gumri, which had some of the worst destruction (OR for residents of Gumri 5.9 [95% CI 4.0-8.8]). Being with someone in the same building at the moment of the earthquake was protective for depression (OR for presence of other people 0.5 [95% CI 0.3-0.6]), and the risk of depression increased with the amount of loss that the family sustained as a result of the earthquake (OR for highest level of loss 2.5 [95% CI 1.3-4.8]). The use of alcohol was protective for depression (OR for those who drink 0.5 [95% CI 0.3-0.8]). In various models of multivariate adjustment and analysis, the increased risk of depression with loss, geographic location, and female gender was maintained. Also, being with someone during the disaster, receiving assistance and support after the earthquake, and alcohol use were protective for depression in these multivariate analyses. Depression is a common sequel to an earthquake. As with our previous study of PTSD, we were able to relate intensity of the disaster and loss to the risk of depression in a general population sample. The role of social support during and after the disaster as a protective mechanism against adverse psychological outcome was highlighted again. Whereas alcohol use in our previous study was not related to PTSD outcome, it is noteworthy that in the present analyses it emerged as a protective factor for depression.

6272. Bisson JI, Chubb HL, Bennett S, Mason M, Jones D, Kynaston H. The prevalence and predictors of psychological distress in patients with early localized prostate cancer. BJU Int. 2002 Jul;90(1):56-61.

OBJECTIVE: To determine the level of psychopathology, traumatic distress and quality of life in men with newly diagnosed clinically localized prostate cancer, the effect on these of a consultation in a combined-specialist early-prostate clinic, and predictors of psychopathology. PATIENTS AND METHODS: Eighty-eight patients were recruited from the combined clinic; they completed a battery of questionnaires including the Hospital Anxiety and Depression Scale (HADS), the revised Impact of Event Scale (IES) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, before their first appointment. Two weeks later they completed the HADS, IES and a patient-satisfaction survey. RESULTS: The overall level of psychopathology varied among the questionnaires used, from 0% on the HADS depression scale, 8% on the HADS anxiety scale and 14% on the IES. Anxiety and traumatic stress symptoms were commoner than depressive symptoms. The quality-of-life scores showed a relatively good level of functioning. Pre-morbid factors and disease status did not predict psychological distress. Younger age was mildly predictive of poorer psychological functioning. Anxiety symptoms reduced slightly after a joint clinic appointment, whereas depressive symptoms showed a slight increase. CONCLUSION: This study suggests that men with early localized prostate cancer have low levels of psychopathology overall. However, some men experience distressing psychological symptoms and it is important that future research is conducted to help develop clear guidelines on the optimal methods of detecting and managing men with prostate cancer who have mental health difficulties.

6273. Brooks TL, Harris SK, Thrall JS, Woods ER. Association of adolescent risk behaviors with mental health symptoms in high school students. J Adolesc Health. 2002 Sep;31(3):240-6.

PURPOSE: To examine the hypothesis that self-reported symptoms of depression and stress may be associated with other risk behaviors. METHODS: A secondary data analysis of the 1992 Massachusetts Adolescent Health Survey involving a representative sample of 2,224 ninth and twelfth grade students was performed. The dichotomous dependent variable was positive if the adolescent reported feeling depressed or stressed for 10 or more days in the past month. Potential independent variables examined were age, gender, race/ethnicity, and 14 risk or protective behaviors: each scored on a seven point scale representing increasing frequency of a behavior in the past month. A four-level sexual risk variable was constructed as well. Associations were assessed using Chi-square, and phi/contingency coefficients, and logistic regression analyses to predict the odds of reporting depression/stress. RESULTS: The mean age of the sample was 16.2 +/- 1.6 years; 52% males; 78% were white, 9% black, 6% Latino, 2% Asian, and 4% other racial/ethnic heritage; 35% reported feeling depressed/stressed > or = 10 days in the past month. A logistic regression model found that feelings of depression/stress were associated with increasing age (OR = 1.09 with each additional year [95% CI, 1.02-1.18]), female gender (3.28 [2.62-4.12]); increasing levels of tobacco use (1.07 [1.01-1.12]), physical fights (1.19 [1.11-1.28]); and non-use of birth control compared with never having been sexually active (1.81 [1.31-2.49]). Independent variables of reporting depression/stress for males included increasing age (1.15 [1.03-1.28]), and physical fights (1.20 [1.10-1.30]), and non-use of birth control compared with never sexually active (1.91 [1.28-2.92]). Independent risk and protective factors for females included tobacco use (1.10 [1.02-1.19]), healthy diet (0.89 [0.83- 0.96]), and always (1.49 [1.03-2.28]) or sometimes used birth control (1.56 [1.03-1.28]) compared with never sexually active. CONCLUSIONS: Female gender had greater than threefold increased odds of reporting depression/stress. Other associations, with some gender differences, include older age, physical fights, non-use of birth control, lack of a healthy diet, and use of tobacco.

6274. Buchsbaum GM, Chin M, Glantz C, Guzick D. Prevalence of urinary incontinence and associated risk factors in a cohort of nuns. Obstet Gynecol. 2002 Aug;100(2):226-9.

OBJECTIVE:To estimate the prevalence of urinary incontinence among a group of nulliparous nuns and to assess risk factors for developing incontinence.METHODS:Information on symptoms of urinary incontinence, as well as medical history and demographic data were obtained from 149 nuns. The prevalence of urinary incontinence was determined, and a logistic regression model was used to estimate the impact of demographic and medical risk factors on the likelihood of incontinence.RESULTS:The mean (+/- standard deviation) age of our sample of nuns was 68 (+/-11.7). All but one were white, 96% were postmenopausal, and 25% were taking hormone replacement therapy (HRT). Their mean body mass index (BMI) was 27.3 +/- 5.6. According to their self-reported symptoms, half the nuns had urinary incontinence. Of these, 22 nuns (30%) had stress incontinence, 18 (24%) had urge incontinence, 26 (35%) had mixed incontinence, and 8 (11%) had urine loss unrelated to stress and urge. More than half the incontinent nuns used sanitary pads for protection. From univariate analyses, statistically significant risk factors for urinary incontinence included BMI, current HRT use, multiple urinary tract infections, hypertension, arthritis, depression, hysterectomy, and previous spinal surgery. From multivariate logistic regression, only BMI, multiple urinary tract infections, and depression remained statistically significant after adjusting for the other variables.CONCLUSION:The prevalence of incontinence in nulliparous, predominantly postmenopausal nuns is similar to rates reported in parous, postmenopausal women. Even in the absence of pelvic floor trauma from childbirth, urine loss is associated with symptoms of stress incontinence more often than with symptoms of urge incontinence.

6275. Champion JD, Shain RN, Piper J, Perdue ST. Psychological distress among abused minority women with sexually transmitted diseases. J Am Acad Nurse Pract. 2002 Jul;14(7):316-24.

PURPOSE: To describe psychological distress among abused minority women with sexually transmitted diseases (STDs) and to identify needs for psychotherapeutic intervention for reduction in abuse, sexual risk behavior and STD. DATA SOURCES: A controlled randomized trial of the effects of a behavioral intervention on STD recurrence. Eligibility was limited to English speaking Mexican-American and African-American women with a current non-viral STD confirmed by laboratory testing (gonorrhea, chlamydia, syphilis or trichomonas). All eligible women who could be contacted were recruited from public-health clinics in San Antonio. T-tests, Chi square and correlation were used to analyze the data. CONCLUSIONS: Women with STD and a history of abuse reported more symptoms of current psychological distress than nonabused women. This psychological distress was present in all dimensions of the SCL-90-R, including somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism. Increased current psychological distress and correlation was found not only for women with reports of sexual abuse but also forms of physical or psychological abuse. The majority of abuse was reportedly experienced during a relationship with a boyfriend or friend/acquaintance. IMPLICATIONS FOR PRACTICE: Abused women with STD may benefit from the identification and assessment of abuse history and psychological distress so that appropriate psychological treatment can accompany medical treatment. The prevalence of woman abuse within a population of women with STD mandates the inclusion of violence in STD prevention programs.

6276. Dalton SO, Boesen EH, Ross L, Schapiro IR, Johansen C. Mind and cancer. do psychological factors cause cancer? Eur J Cancer. 2002 Jul;38(10):1313-23. Review.

We have reviewed the evidence for an association between major life events, depression and personality factors and the risk for cancer. We identified and included only those prospective or retrospective studies in which the psychological variable was collected independently of the outcome. The evidence failed to support the hypothesis that major life events are a risk factor for cancer. The evidence was inconsistent for both depression and personality factors. Chance, bias or confounding may explain this result, as many of the studies had methodological weaknesses. The generally weak associations found, the inconsistency of the results, the unresolved underlying biological mechanism and equivocal findings of dose-response relationships prevent a conclusion that psychological factors are established risk factors. However, certain intriguing findings warrant further studies, which must, however, be well conducted and large and include detailed information on confounders.

6277. Das S. Depression in medical students [letters] Indian Practitioner. 2002 Apr; 55(4): 235-6.

ABSTRACT: Depression is the most common mental disease affecting young medical students. Medical students are unable to cope up with stress and hence suffer from this disorder. In many cases, students fail to seek necessary care for this health problem. Over years, little attention has been paid to this growing mental disorder. This has resulted in decline in individual skill of many budding doctors. Unless proper care and treatment are given, many young medicos would succumb to this growing mental disorder.

6278. el-Serag HB, Kunik M, Richardson P, Rabeneck L. Psychiatric disorders among veterans with hepatitis C infection. Gastroenterology. 2002 Aug;123(2):476-82.

BACKGROUND & AIMS: The presence of psychiatric, drug-, and alcohol-use disorders in hepatitis C virus (HCV)-infected patients may influence their management and prognosis. The frequency and the risk for these disorders among HCV-infected patients are unknown. METHODS: We identified all HCV-infected veteran patients who were hospitalized during 1992-1999 and searched the inpatient and outpatient computerized files for predefined psychiatric, drug-, and/or alcohol-use disorders. We then performed a case-control study among Vietnam veterans; controls without HCV were randomly chosen from hospitalized patients. RESULTS: We identified 33,824 HCV-infected patients, in whom 86.4% had at least one past or present psychiatric, drug-, or alcohol-use disorder recorded. However, only 31% had active disorders as defined by hospitalization to psychiatric or drug-detoxification bed sections. There were 22,341 HCV-infected patients from the Vietnam period of service (cases) who were compared with 43,267 patients without HCV (controls). Cases were more likely to have depressive disorders (49.5% vs. 39.1%), posttraumatic stress disorder (PTSD) (33.5% vs. 24.5%), psychosis (23.7% vs. 20.9%), bipolar disorder (16.0% vs. 12.6%), anxiety disorders (40.8% vs. 32.9%), alcohol (77.6% vs. 45.0%), and drug-use disorders (69.4% vs. 31.1%). In multivariable regression analyses that adjust for age, sex, and ethnicity, drug use, alcohol-use, depression, PTSD, and anxiety remained strongly associated with HCV. CONCLUSIONS: Several psychiatric, drug-, and alcohol-use disorders are commonly found among HCV-infected veterans compared with those who are not infected. At least one third of these patients have active disorders. A multidisciplinary approach to the management of HCV-infected patients is needed.

6279. Feinstein A, Owen J, Blair N. A hazardous profession: war, journalists, and psychopathology. Am J Psychiatry. 2002 Sep;159(9):1570-5.

OBJECTIVE: War journalists often confront situations of extreme danger in their work. Despite this, information on their psychological well-being is lacking. METHOD: The authors used self-report questionnaires to assess 140 war journalists, who recorded symptoms of posttraumatic stress disorder (PTSD) (with the Impact of Event Scale-Revised), depression (with the Beck Depression Inventory-II), and psychological distress (with the 28-item General Health Questionnaire). To control for stresses generic to all journalism, the authors used the same instruments to assess 107 journalists who had never covered war. A second phase of the study involved interviews with one in five journalists from both groups, using the Structured Clinical Interview for Axis I DSM-IV Disorders. RESULTS: The rates of response to the self-report questionnaires were approximately 80% for both groups. There were no demographic differences between groups. Both male and female war journalists had significantly higher weekly alcohol consumption. The war journalists had higher scores on the Impact of Event Scale and the Beck Depression Inventory. Their lifetime prevalence of PTSD was 28.6%, and the rates were 21.4% for major depression and 14.3% for substance abuse. War journalists were not, however, more likely to receive treatment for these disorders. CONCLUSIONS: War journalists have significantly more psychiatric difficulties than journalists who do not report on war. In particular, the lifetime prevalence of PTSD is similar to rates reported for combat veterans, while the rate of major depression exceeds that of the general population. These results, which need replicating, should alert news organizations that significant psychological distress may occur in many war journalists and often goes untreated.

6280. Hughes P, Turton P, Hopper E, Evans CD. Assessment of guidelines for good practice in psychosocial care of mothers after stillbirth: a cohort study. Lancet. 2002 Jul 13;360(9327):114-8.

BACKGROUND: Most maternity units have good practice protocols, advising that after stillbirth parents should be encouraged to see and hold their dead infant. Our aim was to assess whether adherence to these protocols is associated with measurably beneficial effects on the psychological health of mother and next-born child. This study forms part of a wider case-control study of the psychological effects of stillbirth. METHODS: We identified 65 women in the pregnancy after stillbirth, and enrolled matched controls for 60 of them. Outcome measures included depression, anxiety, and post-traumatic-stress disorder (PTSD) in pregnancy and 1 year after the next birth, and disorganised attachment behaviour in the next-born infant. Comparison variables included seeing and holding the stillborn infant, having a funeral, and keeping mementoes. FINDINGS: Behaviours that promote contact with the stillborn infant were associated with worse outcome. Women who had held their stillborn infant were more depressed than those who only saw the infant, while those who did not see the infant were least likely to be depressed (13 of 33, 39%, vs three of 14, 21%, vs one of 17, 6%; p=0.03). Women who had seen their stillborn infant had greater anxiety (p=0.02) and higher symptoms of PTSD than those who had not (p=0.02), and their next-born infants were more likely to show disorganised attachment behaviour (18 of 43, 42%, vs one of 12, 8%, p=0 x 04). Having a funeral and keeping mementoes were not associated with further adverse outcomes, but small numbers limited interpretation. INTERPRETATION: Our findings do not support good-practice guidelines, which state that failure to see and hold the dead child could have adverse effects on parents' mourning.

6281. Langer G. Psychological sequelae of September 11. N Engl J Med. 2002 Aug 8;347(6):443-5; discussion 443-5. No abstract.

6282. Mead DE. Marital distress, co-occurring depression, and marital therapy: a review. J Marital Fam Ther. 2002 Jul;28(3):299-314. Review.

This article reviews several factors that contribute to marital distress and co-occurring depression and also reviews empirically supported therapies. Gender contributes to marital distress and depression but does not appear to be the cause of either. Marital distress and depression appear to have bidirectional influence on each other. The depressed spouse's depression has a marked impact on the marital adjustment of the nondepressed spouse. Both marital distress and depression appear to be chronic. It is recommended that treatment be designed to help couples be supportive of each another, to adapt, and to cope with the depressive symptoms within the framework of their ongoing marital relations.

6283. Motzer SA, Jarrett M, Heitkemper MM, Tsuji J. Natural killer cell function and psychological distress in women with and without irritable bowel syndrome. Biol Res Nurs. 2002 Jul;4(1):31-42.

The primary purpose of this exploratory study was to compare percentages of natural killer (NK) cells and activated NK and T cells, and both cytotoxic and in vitro cytokine production activity in women with and without symptomatic irritable bowel syndrome (IBS). A secondary purpose was to examine the relationships of psychological distress and low sense of coherence with immune function indicators and stress hormones. NK cell percentage and activity have been shown to vary in response to many psychological and physiological stressors. The authors compared 2 groups of women: symptomatic IBS (n = 12) and control (n = 12). Between-subject variability for all immune measures was large. The percentage of activated NK and Tcells was significantly lower in the IBS group compared to control (Mann-Whitney U = 30, P = 0.05). Relationships were significant between activated NK and T cell percentage and depression, anxiety, and overall distress (r = -0.54, -0.49, and -0.47, respectively, P < 0.03) and between interferon-gamma production and anxiety (r = -0.45, P < 0.03). There was a trend toward a positive relationship between sense of coherence and NK cytotoxicity (r = 0.39, P = 0.11). Thesefindings are important because they suggest that nursing interventions targeting ongoing physical and psychological distress might also be helpful in improving immune function.

6284. Paterniti S, Niedhammer I, Lang T, Consoli SM. Psychosocial factors at work, personality traits and depressive symptoms. Longitudinal results from the GAZEL Study. Br J Psychiatry. 2002 Aug;181:111-7.

BACKGROUND: An association between stressful job conditions and depressive symptoms has been reported. This association could be explained by personality traits. AIMS: To examine the relationship between psychosocial factors at work and changes in depressive symptoms, taking into account personality traits. METHOD: The role of occupational characteristics, psychosocial stress and personality traits in predicting an increase of depressive symptoms was evaluated in 7729 men and 2790 women working at the French National Electricity and Gas Company, with a 3-year follow-up. RESULTS: In men, high decision latitude was predictive of a decrease in the Centre for Epidemiologic Studies - Depression scale (CES-D) scores. In both genders, high job demands and low social support at work were predictive of increased scores, irrespective of personality traits and covariates. CONCLUSIONS: Adverse psychosocial work conditions are predictors of depressive symptom worsening, independent of personality traits.

6285. Rosenberg PB, Mehndiratta RB, Mehndiratta YP, Wamer A, Rosse RB, Balish M. Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. J Neuropsychiatry Clin Neurosci. 2002 Summer;14(3):270-6.

Twelve patients with comorbid posttraumatic stress disorder (PTSD) and major depression underwent repetitive transcranial magnetic stimulation (rTMS) to left frontal cortex as an open-label adjunct to current antidepressant medications. rTMS parameters were as follows: 90% of motor threshold, 1 Hz or 5 Hz, 6,000 stimuli over 10 days. Seventy-five percent of the patients had a clinically significant antidepressant response after rTMS, and 50% had sustained response at 2-month follow-up. Comparable improvements were seen in anxiety, hostility, and insomnia, but only minimal improvement in PTSD symptoms. Left frontal cortical rTMS may have promise for treating depression in PTSD, but there may be a dissociation between treating mood and treating core PTSD symptoms. Sayal K, Checkley S, Rees M, Jacobs C, Harris T, Papadopoulos A, Poon L. Effects of social support during weekend leave on cortisol and depression ratings: a pilot study. J Affect Disord. 2002 Sep;71(1-3):153-7.

6286. Sharpe M, Wilks D. Fatigue. BMJ. 2002 Aug 31;325(7362):480-3. Review. No abstract.

6287. Yen S, Shea MT, Battle CL, Johnson DM, Zlotnick C, Dolan-Sewell R, Skodol AE, Grilo CM, Gunderson JG, Sanislow CA, Zanarini MC, Bender DS, Rettew JB, McGlashan TH. Traumatic exposure and posttraumatic stress disorder in borderline, schizotypal, avoidant, and obsessive-compulsive personality disorders: findings from the collaborative longitudinal personality disorders study. J Nerv Ment Dis. 2002 Aug;190(8):510-8.

The association between trauma and personality disorders (PDs), while receiving much attention and debate, has not been comprehensively examined for multiple types of trauma and PDs. The authors examined data from a multisite study of four PD groups: schizotypal, borderline (BPD), avoidant, and obsessive-compulsive, and a major depression comparison group. Rates of

traumatic exposure to specific types of trauma, age of first trauma onset, and rates of posttraumatic stress disorder are compared. Results indicate that BPD participants reported the highest rate of traumatic exposure (particularly to sexual traumas, including childhood sexual abuse), the highest rate of posttraumatic stress disorder, and youngest age of first traumatic event. Those with the more severe PDs (schizotypal, BPD) reported more types of traumatic exposure and higher rates of being physically attacked (childhood and adult) when compared to other groups. These results suggest a specific relationship between BPD and sexual trauma (childhood and adult) that does not exist among other PDs. In addition, they support an association between severity of PD and severity of traumatic exposure, as indicated by earlier trauma onset, trauma of an assaultive and personal nature, and more types of traumatic events.

Heart Disease:

6289. Alfredsson L, Hammar N, Fransson E, de Faire U, Hallqvist J, Knutsson A, Nilsson T, Theorell T, Westerholm P. Job strain and major risk factors for coronary heart disease among employed males and females in a Swedish study on work, lipids and fibrinogen. Scand J Work Environ Health. 2002 Aug;28(4):238-48.

OBJECTIVES: The aim of this study was to analyze the relationship of job strain (high psychological job demands and low decision latitude) to hypertension, serum lipids, and plasmafibrinogen. METHODS: The study population consisted of employed persons between the ages of 15 and 64 years in the counties of Stockholm, Vasternorrland, and Jamtland, Sweden. The data collection was carried out during 1992-1998. A total of 10,382 subjects participated in a medical examination and completed a questionnaire. RESULTS: No strong associations were found between job strain and plasma fibrinogen. The males reporting job strain had lower levels of total cholesterol and high-density lipoprotein cholesterol than the other males. Similar tendencies were found for the females. The females, but not the males, with job strain had an increased prevalence of hypertension when compared with the subjects with relaxed psychosocial work characteristics. In the subgroups of younger males and females an adverse association between job strain and the ratio between low-density and high-density lipoprotein cholesterol was noted. CONCLUSIONS: The results do not support the hypothesis that job strain has an adverse impact on serum total cholesterol and plasma fibrinogen levels. They suggest that an increased risk of coronary heart disease in association with job strain, if causal, is mediated by other factors, possibly partly by hypertension and low levels of high-density lipoprotein cholesterol.

6290. Bonetti PO, Wilson SH, Rodriguez-Porcel M, Holmes DR Jr, Lerman LO, Lerman A. Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering. J Am Coll Cardiol. 2002 Aug 7;40(3):546-54.

OBJECTIVES; This study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia. BACKGROUND: Simvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown. METHODS: Pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated. RESULTS: Total and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05). CONCLUSIONS: These findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering.

6291. Bronzwaer JG, Zeitz C, Visser CA, Paulus WJ. Endomyocardial nitric oxide synthase and the hemodynamic phenotypes of human dilated cardiomyopathy and of athlete's heart. Cardiovasc Res. 2002 Aug 1;55(2):270-8; discussion 225-8.

OBJECTIVE: In dilated cardiomyopathy and in athlete's heart, progressive LV dilatation is accompanied by rightward displacement of the diastolic LV pressure-volume relation. In dilated cardiomyopathy, an increase in diastolic LV stiffness can limit this rightward displacement thereby decreasing LV systolic performance. Because nitric oxide (NO) reduces diastolic LV stiffness, the present study relates diastolic LV stiffness and LV systolic performance to intensity of endomyocardial NO synthase (NOS) gene expression in dilated cardiomyopathy and in athlete's heart. METHODS: Microtip LV pressures, conductance-catheter or angiographic LV volumes, echocardiographic LV wall thicknesses and snap-frozen LV endomyocardial biopsies were obtained in 33 patients with dilated cardiomyopathy and in three professional cyclists referred for sustained ventricular tachycardia. Intensity of LV endomyocardial inducible NOS (NOS2) and constitutive NOS (NOS3) gene expression was determined using quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Dilated cardiomyopathy patients with higher diastolic LV stiffness-modulus and lower LV stroke work had lower NOS2 and NOS3 gene expression at any given level of LV end-diastolic wall stress. The intensity of NOS2 and NOS3 gene expression observed in athlete's heart was similar to dilated cardiomyopathy with low LV diastolic stiffness-modulus and preserved LV stroke work. CONCLUSIONS: High LV endomyocardial NOS gene expression is observed in athlete's heart and in dilated cardiomyopathy with low diastolic LV stiffness and preserved LV stroke work. Favourable effects on the hemodynamic phenotype of high LV endomyocardial NOS gene expression could result from a NO-mediated decrease in diastolic LV stiffness and a concomitant rise in LV preload reserve.

6292. Cossette S, Frasure-Smith N, Lesperance F. Nursing approaches to reducing psychological distress in men and women recovering from myocardial infarction. Int J Nurs Stud. 2002 Jul;39(5):479-94.

-This paper examines the types of nursing approaches associated with reductions in psychological distress in post-myocardial infarction patients (n=275 men; 156 women) who took part in a home-based psychosocial nursing Intervention program (Montreal Heart Attack Readjustment Trial). We found that three types of emotionally supportive approaches including reassurance/encouragement, listening and the provision of advice varied in their links to reduction in distress depending on patients' types of concerns. There were also gender differences in the way directive and collaborative intervention approaches were related to changes in distress.

6293. Elhendy A, Chandrasekaran K, Gersh BJ, Mahoney D, Burger KN, Pellikka PA. Functional and prognostic significance of exercise-induced ventricular arrhythmias in patients with suspected coronary artery disease. Am J Cardiol. 2002 Jul 15;90(2):95-100.

Our aims were to assess (1) the relation between exercise-induced ventricular arrhythmia (VA) and myocardial wall motion abnormalities during exercise echocardiography in patients with suspected coronary artery disease (CAD), and (2) the effect of this relation on outcome. We studied the clinical and prognostic significance of exercise-induced VA in 1,460 patients (mean age 64 +/- 10 years; 867 men) with intermediate pretest probability of CAD and no history of previous myocardial infarction or revascularization who underwent exercise echocardiography. Exercise-induced VA occurred in 146 patients (10%). Compared with patients without VA, those with VA had a greater prevalence of abnormal exercise echocardiographic findings (48% vs 29%, p = 0.001) and ischemia on exercise echocardiography (39% vs 22%, p = 0.001), greater increase in wall motion score index with exercise (0.14 +/- 0.28 vs 0.06 +/- 0.18, p <0.0001), and a greater percentage of abnormal segments with exercise (21 +/- 30% vs 9 +/- 19%, p <0.0001). During follow-up (median 2.7 years), cardiac death and nonfatal myocardial infarction occurred in 36 patients. In multivariate analysis of combined clinical and exercise stress test variables, independent predictors of cardiac events were exercise-induced VA (chi-square 4.7, p = 0.03) and exercise heart rate (chi-square 18, p = 0.0001). The percentage of abnormal myocardial segments with exercise echocardiography was the most powerful predictor of VA (chi-square 31, p = 0.0001) and cardiac events (chi-square 15, p = 0.0001). In patients with suspected CAD, exercise-induced VA is associated with a greater risk of cardiac death and nonfatal myocardial infarction. This risk is attributed to the relation between VA and the extent and severity of left ventricular functional abnormalities with exercise.

6294. Friedman EH. Neurobiology of psychosocial treatment of mental stress-induced myocardial ischemia in men. Am J Cardiol. 2002 Jul 1;90(1):86-7. No abstract.

6295. Houtveen JH, Rietveld S, de Geus EJ. Contribution of tonic vagal modulation of heart rate, central respiratory drive, respiratory depth, and respiratory frequency to respiratory sinus arrhythmia during mental stress and physical exercise. Psychophysiology. 2002 Jul;39(4):427-36.

This study tested various sources of changes in respiratory sinus arrhythmia (RSA). Twenty-two healthy participants participated in three experimental conditions (mental stress, relaxation, and mild physical exercise) that each consisted of three breathing parts (normal breathing, breathing compressed room air, and breathing compressed 5% CO2-enriched air). Independent contributions to changes in RSA were found for changes in tonic vagal modulation of heart rate, central respiratory drive (i.e., PaCO2), respiratory depth, and respiratory frequency. The relative contributions to changes in RSA differed for mental stress and physical exercise. It is concluded that uncorrected RSA will suffice to index within-subject changes in tonic vagal modulation of heart rate in most situations. However, if the central respiratory drive is expected to change, RSA should ideally be corrected for changes in PaCO2, respiratory depth, and respiratory frequency.

6296. Kennedy JE, Abbott RA, Rosenberg BS. Changes in spirituality and well-being in a retreat program for cardiac patients. Altern Ther Health Med. 2002 Jul-Aug;8(4):64-6, 68-70, 72-3.

CONTEXT: Many epidemiological studies indicate that spirituality or religion are positively correlated with health measures, but research is needed on interventions that change spirituality to verify that it actually affects health and to justify suggestions that changes in spiritual practices or beliefs may have health benefits. However, it is not clear that health interventions can influence spirituality or which techniques are effective. OBJECTIVE: To evaluate whether participation in a retreat program for cardiac patients and their partners resulted in changes in spirituality and whether changes in spirituality were related to changes in well-being meaning in life, anger, and confidence in handling problems. DESIGN: Participants filled out questionnaires before and after participating in the retreat. SETTING: Retreats were sponsored by the Health Promotion and Wellness Program, University of Wisconsin-Stevens Point, and were held in a remote training center. PARTICIPANTS: Notices were sent to cardiac rehabilitation programs and directly to heart patients, resulting in the enrollment of 72 first-time participants. INTERVENTION: The 2.5-day educational retreats included discussion and opportunities to experience healthy lifestyle options. Exercise, nutrition, stress management techniques, communication skills that enhance social support, and spiritual principles of healing were incorporated. Experiential practices included yoga, meditation, visualization, and prayer. RESULTS: Of the participants, 78% reported increased spirituality after the retreat. Changes in spirituality were positively associated with increased well-being meaning in life, confidence in handling problems, and decreased tendency to become angry. CONCLUSIONS: Programs that explore spirituality in a health context can result in increased spirituality that is associated with increased well-being and related measures. Many patients and their families want to integrate the spiritual and health dimensions of their lives. Further work is needed to develop healthcare settings that can support this integration.

6297. Lewthwaite J, Owen N, Coates A, Henderson B, Steptoe A. Circulating human heat shock protein 60 in the plasma of British civil servants: relationship to physiological and psychosocial stress. Circulation. 2002 Jul 9;106(2):196-201.

BACKGROUND: The Whitehall cohort studies (I and II) of British civil servants have identified sociodemographic, psychosocial, and biological risk factors for coronary heart disease (CHD). To identify mechanisms responsible for susceptibility to CHD, specific biological markers of stress are increasingly being measured. One marker linked to susceptibility to CHD is heat shock protein (Hsp) 60. METHODS AND RESULTS: Blood was taken from 229 civil servants (126 men and 103 women) in the Whitehall II cohort drawn equally from the range of employment grades. Plasma was assayed for levels of Hsp60, tumor necrosis factor alpha (TNFalpha), C-reactive protein, von Willebrand factor, high density lipoprotein (HDL), total cholesterol, and total/HDL ratio. Psychosocial measures included socioeconomic status, psychological distress, and social isolation. The majority of the participants had Hsp60 in their plasma, and approximately 20% had >1000 ng/mL of this protein (a concentration likely to induce biological effects). A positive association between plasma Hsp60 and TNFalpha and a negative association with von Willebrand factor was found. There was also a significant association between elevated Hsp60 levels, low socioeconomic status, and social isolation, together with an association with psychological distress in women. CONCLUSIONS: The majority of participants exhibited Hsp60 in their plasma, and there was evidence of an association between levels of this stress protein and the proinflammatory cytokine, TNFalpha, and with various psychosocial measures.

6298. Petrie KJ, Cameron LD, Ellis CJ, Buick D, Weinman J. Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial. Psychosom Med. 2002 Jul-Aug;64(4):580-6.

OBJECTIVE: This study was designed to examine whether a brief hospital intervention designed to alter patients' perceptions about their myocardial infarction (MI) would result in a better recovery and reduced disability. DESIGN: In a prospective randomized study, 65 consecutive patients with their first MI aged were assigned to receive an intervention designed to alter their perceptions about their MI or usual care from rehabilitation nurses. Patients were assessed in hospital before and after the intervention and at 3 months after discharge from hospital. RESULTS: The intervention caused significant positive changes in patients' views of their MI. Patients in the intervention group also reported they were better prepared for leaving hospital (p<.05) and subsequently returned to work at a significantly faster rate than the control group (p<.05). At the 3-month follow-up, patients in the intervention group reported a significantly lower rate of angina symptoms than control subjects (14.3 vs. 39.3, p<.03). There was no significant differences in rehabilitation attendance between the two groups. CONCLUSIONS: An in-hospital intervention designed to change patients' illness perceptions can result in improved functional outcome after MI.

6299. Roger VL, Jacobsen SJ, Weston SA, Pellikka PA, Miller TD, Bailey KR, Gersh BJ. Sex differences in evaluation and outcome after stress testing. Mayo Clin Proc. 2002 Jul;77(7):638-45.

OBJECTIVE: To examine sex differences in evaluation and outcome after stress testing for coronary artery disease (CAD) in a geographically defined cohort. SUBJECTS AND METHODS: Subjects were residents of Olmsted County, Minnesota, who underwent an initial stress test between January 1, 1987, and December 31, 1990. End points included referral for coronary angiography, death, and cardiac events, defined as cardiac death, nonfatal myocardial infarction, or congestive heart failure. RESULTS: A total of 2276 men and 1270 women under went stress tests. Women were older and had more risk factors and comorbidities (P < .05). Among persons without documented CAD (86% of the cohort), the median probability of CAD was 11% (interquartile range, 5%-25%) for men and 8% (interquartile range, 2%-31%) for women (P < .001). Within 6 months after stress testing, 9% of men and 7% of women underwent coronary angiography. Among persons without documented CAD, there was no sex difference in referral for angiography when the stress test result was negative. When the test result was positive, men were more likely to be referred for angiography (adjusted odds ratio [OR] for male sex, 2.02; 95% confidence interval [CI], 1.21-3.38; P = .008). After adjusting for the predicted probability of CAD, this association was no longer detected (adjusted OR for male sex, 0.67; 95% CI, 0.26-1.73; P = .41). Among persons with documented CAD, no sex difference was noted. After a mean +/- SD follow-up of 7.6 +/- 2.7 years and among persons without documented CAD, male sex was associated with a higher adjusted risk of death (relative risk for male sex, 1.40; 95% CI, 1.05-1.86; P = .02) and cardiac events (relative risk for male sex, 1.67; 95% CI, 1.24-2.26; P < .001). Among persons with documented CAD, no sex difference in outcome was noted. CONCLUSION: These population-based data indicate that, when the diagnosis of CAD was not established, there was a greater use of angiography among men with positive stress test results, which could be attributed to the increased probability of CAD in men. In the absence of documented CAD, men fared worse than women, with an increase in the risk of death and cardiac events. Among persons with documented CAD, no sex difference in use of angiography and outcome was noted.

6300. Schmermund A, Mohlenkamp S, Stang A, Gronemeyer D, Seibel R, Hirche H, Mann K, Siffert W, Lauterbach K, Siegrist J, Jockel KH, Erbel R. Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Risk Factors, Evaluation of Coronary Calcium and Lifestyle. Am Heart J. 2002 Aug;144(2):212-8.

BACKGROUND: In view of consistently high cardiovascular morbidity and mortality rates, international efforts are aimed at developing tools for more precise risk prediction to allow preventive treatment targeted at high-risk individuals. Direct visualization of anatomic, preclinical atherosclerotic disease has the potential for individualized risk discrimination. Further, a variety of risk factors are actively evaluated, including markers of the activity of atherosclerotic disease, thrombogenic risk, and genetic polymorphisms. METHODS: The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) study is a population-based, prospective cohort study of the comparative value of modern risk stratification techniques for "hard" cardiac events. It is designed and powered to define the relative risk associated with the specific extent of coronary atherosclerosis measured by means of electron-beam computed tomography (EBCT)-derived coronary calcium quantities for myocardial infarction and cardiac death in 5 years in 4200 males and females aged 45 to 75 years in an unselected urban population from the large, heavily industrialized Ruhr area. Additionally, the predictive values of conventional cardiovascular risk factors, new candidate and socioeconomic risk factors, certain genetic polymorphisms, and direct signs of subclinical disease are examined with the ankle-brachial index, resting and stress electrocardiograms, and determination of carotid artery intima-media thickness. Prospective clinical risk-benefit and health economic analyses are an inherent part of the study. Study findings with established clinical significance are reported to the participants, but the EBCT findings are withheld until the conclusion of the study. CONCLUSIONS: The Heinz Nixdorf RECALL study will define appropriate methods for identifying high-risk subgroups in the general urban population who may derive the greatest benefit from preventive treatment.

6301. Stalnikowicz R, Tsafrir A. Acute psychosocial stress and cardiovascular events. Am J Emerg Med. 2002 Sep;20(5):488-91. Review.

-Stressful life events can trigger acute myocardial infarction and sudden cardiac death. Victims of natural disasters, such as earthquakes and other conditions of extreme stress should be evaluated for physical injuries as well as for cardiac disease. Copyright 2002, Elsevier Science (USA). All rights reserved.

6302. Tak YR, McCubbin M. Family stress, perceived social support and coping following the diagnosis of a child's congenital heart disease. J Adv Nurs. 2002 Jul;39(2):190-8.

BACKGROUND: Congenital heart disease (CHD) is now estimated to be the second most prevalent chronic illness. A child's chronic illness may have effects that have pervasive consequences for family life. Recently, attention has focused on resiliency variables, especially social support and coping strategy, regulating the impact of stress. In the resiliency model of family stress, adjustment and adaptation, social support is viewed as one of the primary moderators or mediators between stress and well-being. AIMS: The purpose of this study was to explore the relationships of family stress, perceived social support, and coping and determine the resiliency factor associated with coping by families who have a child with chronic illness. DESIGN: In a secondary analysis of a large longitudinal study, the sample consisted of 92 families who had a child under age 12 who was newly diagnosed with CHD within the last 3-4 months. FINDINGS: Results from regression analysis revealed that perceived social support operated as a resiliency factor between family stress and both parental and family coping. Child and family characteristics appeared to be the important predictors of perceived social support and parental coping. Although perceived social support appeared to be an important predictor of parental and family coping, neither the moderating nor mediating model was supported in full but partial causal relations were confirmed. CONCLUSIONS: Findings provided evidence for the theoretical and empirical significance of perceived social support as a predictor of family coping. Further, these findings suggest that perceived social support is a factor influencing the resiliency of relatively high-risk groups of families who have a child with chronic illness.

6303. Torres MR, Short L, Baglin T, Case C, Gibbs H, Marwick TH. Usefulness of clinical risk markers and ischemic threshold to stratify risk in patients undergoing major noncardiac surgery. Am J Cardiol. 2002 Aug 1;90(3):238-42.

The risk of cardiac events in patients undergoing major noncardiac surgery is dependent on their clinical characteristics and the results of stress testing. The purpose of this study was to develop a composite approach to defining levels of risk and to examine whether different approaches to prophylaxis influenced this prediction of outcome. One hundred forty-five consecutive patients (aged 68 +/- 9 years, 79 men) with >1 clinical risk variable were studied with standard dobutamine-atropine stress echo before major noncardiac surgery. Risk levels were stratified according to the presence of ischemia (new or worsening wall motion abnormality), ischemic threshold (heart rate at development of ischemia), and number of clinical risk variables. Patients were followed for perioperative events (during hospital admission) and death or infarction over the subsequent 16 +/- 10 months. Ten perioperative events occurred in 105 patients who proceeded to surgery (10%, 95% confidence interval [CI] 5% to 17%), 40 being cancelled because of cardiac or other risk. No ischemia was identified in 56 patients, 1 of whom (1.8%) had a perioperative infarction. Of the 49 patients with ischemia, 22 (45%) had 1 or 2 clinical risk factors; 2 (9%, 95% CI 1% to 29%) had events. Another 15 patients had a high ischemic threshold and 3 or 4 risk factors; 3 (20%, 95% CI 4% to 48%) had events. Twelve patients had a low ischemic threshold and 3 or 4 risk factors; 4 (33%, 95% CI 10% to 65%) had events. Preoperative myocardial revascularization was performed in only 3 patients, none of whom had events. Perioperative and long-term events occurred despite the use of beta blockers; 7 of 41 beta blocker-treated patients had a perioperative event (17%, 95% CI 7% to 32%); these treated patients were at higher anticipated risk than untreated patients (20 +/- 24% vs 10 +/- 19%, p =0.02). The total event rate over late follow-up was 13%, and was predicted by dobutamine-atropine stress echo results and heart rate response.

Hypertension:

6304. Alfredsson L, Hammar N, Fransson E, de Faire U, Hallqvist J, Knutsson A, Nilsson T, Theorell T, Westerholm P. Job strain and major risk factors for coronary heart disease among employed males and females in a Swedish study on work, lipids and fibrinogen. Scand J Work Environ Health. 2002 Aug;28(4):238-48.

6305. Dishman RK, Jackson EM, Nakamura Y. Influence of fitness and gender on blood pressure responses during active or passive stress. Psychophysiology. 2002 Sep;39(5):568-76.

We examined hemodynamic and autonomic components of blood pressure responses during active and passive stressor tasks in a sample of young, normotensive men and women who were physically active but differed on fitness (i.e., VO2peak). During the hand cold pressor, increases in systolic blood pressure were inversely related to fitness among women but not men. Regardless of gender, fitter participants had a greater increase in cardiac pace during mental arithmetic, coherent with a decreased cardiac-vagal component of heart rate variability, and a greater compensatory reduction in stroke volume. Fitness was otherwise unrelated to changes in cardiac output and vascular resistance during the stressor tasks. Our findings suggest that cardiorespiratory fitness augments the cardiac-vagal withdrawal that is characteristic of mental arithmetic. The blunted systolic blood pressure response to the hand cold pressor among fitter women suggests that cardiorespiratory fitness should be considered as a covariate in studies that examine the hand cold pressor as a predictor of future hypertension among women.

6306. Ewart CK, Jorgensen RS, Suchday S, Chen E, Matthews KA. Measuring stress resilience and coping in vulnerable youth: the Social Competence Interview. Psychol Assess. 2002 Sep;14(3):339-52.

A brief interview to measure stress coping capabilities was developed and tested in 4 samples of African American and White adolescents in low-income neighborhoods of 2 large U.S. cities. The Social Competence Interview (SCI) is a 10-min social stressor that assesses physiological and social emotional responses to a recurring real-life problem. A new behavioral coding system using audiotapes permits reliable and valid assessment of components of social competence, including Interpersonal Skills (expressiveness, empathy), Goal-Oriented Strivings in coping (self defense, social acceptance, competitiveness, stimulation-pleasure, approval, self improvement), and Social Impact (high vs. low affiliation/control). High SCI expressiveness and self-defensive striving create a critical-aggressive social impact, which is correlated with increased hostility and anger.

6307. Jackson EM, Dishman RK. Hemodynamic responses to stress among black women: fitness and parental hypertension. Med Sci Sports Exerc. 2002 Jul;34(7):1097-104; discussion 1105.

PURPOSE: We compared hemodynamic aspects of the relationship between cardiorespiratory fitness and blood pressure changes during and after laboratory stress in young black women with or without parental history of hypertension. METHODS: Participants were 30 normotensive, black American women having low to moderate fitness levels (i.e., VO2peak) assessed by cycle ergometry who performed standard active and passive coping laboratory stressors. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance (TPR), calf blood flow (CBF), and calf vascular resistance (CVR) were assessed during exposure to forehead and hand cold pressors, and mental arithmetic, as well as during recovery after the tasks. RESULTS: Fitness was positively related to increases in either TPR or CVR during each stressor. In contrast, fitness was positively related to blunted blood pressure during or after passive stress (i.e., hand or forehead cold) and enhanced recovery of blood pressure and TPR after the active stressor (i.e., mental arithmetic); effects of fitness on the vascular responses during and after mental arithmetic were stronger among women having a negative history of parental hypertension. CONCLUSION: The findings confirm our previous report that fitness blunts systolic blood pressure response during the hand cold pressor in young women. They also suggest that future studies of fitness and blood pressure reactivity during stress should focus on the regulation of vascular responses and their recovery after stress. Weaker effects of VO2peak after mental arithmetic in the positive history group indicate that the level of fitness required to modify recovery from mental stress among black American women may differ according to parental history of hypertension.

6308. Kumar P; Desai VK; Kosambia JK. Prevalence of hypertension amongst the employees of a mega industry of south Gujarat Indian Journal of Community Medicine. 2002 Jan-Mar; 27(1): 19-25.

ABSTRACT: Research question: What is the prevalence of hypertension in the employees of a mega industry? Objective: To find out of prevalence of hypertension and the impact of various risk factors on it and suggest the remedial measures. Study design: Population based cross-sectional study during 1994- 95. Settings: A mega industry located in South Gujarat. Participants: 1300 employees of the industry. Results: Coverage rate of study population was only 76 percent. The prevalence of hypertension was high (24 percent). Hypertension was more in general shift workers and in certain sections (transport, finance and accounts, fire brigade, security etc.). Prevalence was also high in persons who were overweight or consuming alcohol and/or tobacco. Treatment compliance amongst 204 "aware" patients was only 17 percent.

6309. Singh N; Syed Sadiq A; Singh V; Singh A. Adaptogens anti stress agents a study focusing Indian plants Antiseptic. 2002 Jun; 99(6): 198-201

6310. von Kanel R, Mills PJ, Ziegler MG, Dimsdale JE. Effect of beta2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress. Am Heart J. 2002 Jul;144(1):68-72.

BACKGROUND: Procoagulant stress responses may contribute to atherosclerosis development and acute coronary thrombosis. In the present study, we examined the role of beta2-adrenergic receptor function and plasma catecholamines in the stress-induced increase in the 2 hypercoagulability markers thrombin-antithrombin III (TAT) complex and fibrin D-dimer (DD). METHODS: Lymphocyte beta2-adrenoreceptor sensitivity and density were assessed at rest, and plasma levels of TAT, DD, epinephrine, and norepinephrine were measured at rest and in response to a standardized mental stress task in 19 normotensive and mildly hypertensive nonmedicated subjects (mean age 38 years, age range 29 to 48 years). RESULTS: The stressor elicited a significant increase in TAT (P =.024), DD (P =.026), and norepinephrine (P =.005). Resting beta2-adrenoreceptor sensitivity (isoproterenol-stimulated cyclic adenosine monophosphate production) plus the norepinephrine change scores (stress minus rest) accounted for 59% of the variance in the absolute TAT increase in response to stress (P =.001). Hypertension status and demographic variables such as sex did not influence the results. CONCLUSIONS: Acute mental stress may trigger a hypercoagulable state evidenced by increased thrombin activity and increased fibrin turnover. Beta2-adrenergic receptor sensitivity and plasma catecholamine activity may mediate the procoagulant response to acute stressors. These mechanisms may help explain the adverse impact of mental stress on the cardiovascular system.

April 2003

6853. Bantel H, Schmitz ML, Raible A, Gregor M, Schulze-Osthoff K.Critical role of NF-kappaB and stress-activated protein kinases in steroid unresponsiveness. FASEB J 2002 Nov;16(13):1832-4

Glucocorticoid resistance is a serious clinical problem in chronic inflammatory diseases, because many patients with rheumatoid arthritis, asthma, or Crohn's disease fail to respond to steroid treatment. The molecular mechanisms underlying this unresponsiveness, however, are completely unknown. The effects of steroids are largely mediated by the interference of the glucocorticoid receptor (GR) with proinflammatory transcription factors. In the present study, we therefore investigated the activation of the transcription factors nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and the upstream kinases p38 and c-Jun N-terminal kinase (JNK) in steroid-sensitive and steroid-resistant patients with Crohn's disease. We demonstrated that steroid-sensitive and steroid-resistant patients reveal a remarkably different cellular activation pattern of these proinflammatory mediators. In steroid-sensitive patients, activation of NF-kappaB, AP-1, p38, and JNK was mainly found in lamina propria macrophages. In contrast, steroid-resistant patients revealed activation of all these mediators mostly in epithelial cells. The functional interference of the proinflammatory mediators with the glucocorticoid response was supported by reporter gene assays. Expression of NF-kappaB and, interestingly, also JNK1 and p38 inhibited the activity of the GR. Thus, our results suggest that steroid resistance is associated with increased epithelial activation of stress-activated protein kinases and NF-kappaB, which might inhibit the anti-inflammatory action of a limited number of GRs.

6854. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002 Dec 6;298(5600):1911-2 . No abstract.

6855. Laube BL, Curbow BA, Costello RW, Fitzgerald ST. A pilot study examining the relationship between stress and serum cortisol concentrations in women with asthma. Respir Med 2002 Oct;96(10):823-8

The mechanism (s) by which stress exacerbates asthma is unknown. One explanation could be a reduction in endogenous serum cortisol concentrations as a result of stress. Our objective was to determine if a reduction in morning serum cortisol concentrations is associated with higher levels of stress in women with asthma. In this pilot study, seven women with a history of allergic-asthma were prospectively assigned to either low, moderate, or high stress groups based on a combination of their level of current stress and their resources to cope with the stress. After stress group assignment, women donated a morning blood sample, which was analyzed for serum cortisol concentration by an independent laboratory whose personnel were blinded to the subjects' stress status. Three women were assigned to the low stress group, two to the moderate stress group and two to the high stress group. Serum cortisol concentrations ranged from 8 to 23 microg/dl, averaging 14 +/- 6 microg/dl. A Spearman rank correlation indicated that serum cortisol concentrations were significantly inversely related to the stress groupings (r(s) = -0.915; P = 0.025). These results suggest that a reduction in morning serum cortisol concentration may be associated with higher levels of stress and lower resources to cope with the stress in women with allergic-asthma.

6856. Paredi P, Kharitonov SA, Barnes PJ. Analysis of expired air for oxidation products. Am J Respir Crit Care Med 2002 Dec 15;166(12 Pt 2):S31-7

Chronic inflammation is a critical feature of chronic obstructive pulmonary disease, cystic fibrosis, and asthma. This inflammation is associated with the increased production of reactive oxygen species or oxidative stress in the lungs. Oxidative stress may have several adverse effects and may amplify the inflammatory process; however, monitoring oxidative stress is difficult and may not be reflected by changes in blood markers. We have therefore developed several noninvasive markers in the exhaled breath that may indicate oxidative stress in the lungs, and we studied these in relationship to the severity of chronic inflammatory lung diseases. We analyzed the exhaled breath for the content of nitric oxide as a marker of inflammation, carbon monoxide as a marker of oxidative stress, and ethane, which is one of the end products of lipid peroxidation. In addition, we measured the concentration of markers of oxidative stress such as isoprostanes in exhaled breath condensate. Our results confirm that there are increased inflammation, oxidative stress, and lipid peroxidation in lung disease, as shown by elevated levels of nitric oxide, carbon monoxide, and ethane, respectively. The finding of lower levels of these gases in patients on steroid treatment and of higher levels in those with more severe lung disease, as assessed by lung function tests and clinical symptoms, reinforces the hypothesis that the noninvasive measurement of exhaled gases maybe useful in monitoring the underlying pathologic pathways of lung disease. Longitudinal studies are required to assess the clinical usefulness of these measurements in the monitoring of chronic inflammatory lung disease.

6857. Singh N; Abbas SS; Singh V; Singh A.Adaptogens - anti stress agents a study focusing Indian plants Antiseptic. 2002 Jul; 99(7): 243-9. No abstract.

6858. Singh N; Syed Sadiq A; Singh V; Singh A .Adaptogens anti stress agents a study focusing Indian plants Antiseptic. 2002 Jun; 99(6): 198-201

ABSTRACT: This article has been presented with a view to acquaint the readers about plant adaptogens/antistress agent. Although relation of stress has been recognized in genesis of diseases long back, a scientific database is still missing. The pharmaco-clinical studies carried out in this regard are a new venture in Stress-Pharmacology. It is meant to provide new research awareness in the field regarding the fact about stress, Stress-disease and their prevention and treatment. This is more important in view of the fact that there are no drugs for such stress-related diseases in the armamentarium of modern drug therapy. Simple animal models like swimming endurance, immobilization induced gastric ulcers, adrenal function during stress, CCI4 hepatotoxicity, anoxia tolerance test, brain neurotransmitters and enzyme and CNS receptors levels of neurohumorals after swimming immobilization and gravitational stress, milk induced leucocytosis, lipid peroxidase assessment for prevention of cell damage through anti-oxidant activity were carried out to evaluate the adaptogenic activity of these plants in rats and mice. Clinical trial in diseases related to stress like bronchial asthma, hypertension, cellular immunity, viral encephalitis, chronic fatigue syndrome were carried out in man.

6859. Wagner CW. The ongoing evaluation of the impact of depression on asthma. Ann Allergy Asthma Immunol 2002 Dec;89(6):540-1. No abstract.

Biochemical Indicators:

6860. Lind C, Gerdes R, Hamnell Y, Schuppe-Koistinen I, von Lowenhielm HB, Holmgren A, Cotgreave IA. Identification of S-glutathionylated cellular proteins during oxidative stress and constitutive metabolism by affinity purification and proteomic analysis.Arch Biochem Biophys 2002 Oct 15;406(2):229-40

Redox modification of proteins is proposed to play a central role in regulating cellular function. However, high-throughput techniques for the analysis of the redox status of individual proteins in complex mixtures are lacking. The aim was thus to develop a suitable technique to rapidly identify proteins undergoing oxidation of critical thiols by S-glutathionylation. The method is based on the specific reduction of mixed disulfides by glutaredoxin, their reaction with N-ethylmaleimide-biotin, affinity purification of tagged proteins, and identification by proteomic analysis. The method unequivocally identified 43 mostly novel cellular protein substrates for S-glutathionylation. These include protein chaperones, cytoskeletal proteins, cell cycle regulators, and enzymes of intermediate metabolism. Comparisons of the patterns of S-glutathionylated proteins extracted from cells undergoing diamide-induced oxidative stress and during constitutive metabolism reveal both common protein substrates and substrates failing to undergo enhanced S-glutathionylation during oxidative stress. The ability to chemically tag, select, and identify S-glutathionylated proteins, particularly during constitutive metabolism, will greatly enhance efforts to establish posttranslational redox modification of cellular proteins as an important biochemical control mechanism in coordinating cellular function.

Depression:

6861. Brennan PA, Hammen C, Katz AR, Le Brocque RM. Maternal depression, paternal psychopathology, and adolescent diagnostic outcomes. J Consult Clin Psychol. 2002 Oct;70(5):1075-85.

The authors examined the relationship between maternal depression, paternal psychopathology, and adolescent diagnostic outcomes in a community sample of 522 Australian families. They also examined whether chronic family stress, father's expressed emotion, and parents' marital satisfaction mediated the relationship between parental psychopathology and adolescent outcomes. Mother's education, child's gender, and family income were covaried in all analyses. Results revealed that maternal depression and paternal depression had an additive effect on youth externalizing disorders. In addition, maternal depression interacted with both paternal depression and paternal substance abuse in predicting youth depression but not youth nondepressive disorders. Chronic family stress and father's expressed emotion appeared to mediate the relationship between parental psychopathology and youth depression.

6862. Chang L, Heitkemper MM. Gender differences in irritable bowel syndrome. Gastroenterology. 2002 Nov;123(5):1686-701.

In the United States and other Western cultures, a greater number of women seek health care services for symptoms of functional pain disorders, including irritable bowel syndrome, than men. Recent clinical trials indicate that gender differences in responsiveness to drug therapy also occur. Several lines of inquiry have focused on explaining this gender-related difference due to the higher prevalence of these disorders in women. Evidence of a physiologic component is based on gender differences in gastrointestinal transit time, visceral sensitivity, central nervous system pain processing, and specific effects of estrogen and progesterone on gut function. Additional factors may play a role, including gender-related differences in neuroendocrine, autonomic nervous system, and stress reactivity, which are related to bowel function and pain. However, the link between these measures and gut motility or sensitivity remains to be clarified. Psychological characteristics, including somatization, depression, and anxiety as well as a history of sexual abuse, may also contribute to gender-related differences in the prevalence of irritable bowel syndrome. Although gender differences in the therapeutic benefit of serotonergic agents have been observed, less is known about potential differences in responsiveness to nondrug therapies for irritable bowel syndrome.

6863. Das S. Depression in medical students [letters] Indian Practitioner. 2002 Apr; 55(4): 235-6 .

6864. Freeman EW, Frye CA, Rickels K, Martin PA, Smith SS. Allopregnanolone levels and symptom improvement in severe premenstrual syndrome. J Clin Psychopharmacol. 2002 Oct;22(5):516-20.

Allopregnanolone is a neuroactive metabolite of progesterone and a barbiturate-like modulator of central gamma-aminobutyric acid receptors that modify a range of behaviors, including the stress response. The aim of this study was to determine the association of allopregnanolone levels with improvement of mood and behavioral symptoms following antidepressant treatment for severe premenstrual syndrome. A second exploratory aim was to determine whether allopregnanolone levels differed between antidepressant and placebo treatments. Serum samples from 46 women who were treated with sertraline, desipramine, or placebo in double-blind conditions were assayed. Improvement was assessed as the percent change from the pretreatment baseline in premenstrual symptoms, which were rated daily by the subjects. Twenty-seven samples were from improved subjects and 19 samples were from unimproved subjects following 2 to 3 months of double-blind treatment. Posttreatment allopregnanolone levels were significantly lower in the improved compared with the unimproved subjects. Improvement was also significantly associated with lower allopregnanolone levels for premenstrual depression and appetite changes. Improvement remained significantly associated with lower allopregnanolone levels after adjustment for treatment, cycle day of blood draw, age, and the interaction of treatment and cycle day. These preliminary results offer the first placebo-controlled evidence of association between allopregnanolone levels and premenstrual syndrome treatment response and suggest the importance of further study of the associations of allopregnanolone with premenstrual syndromes and the role of allopregnanolone in response to antidepressant medications.

6865. Garland MR. Cortisol, stress and depression. Br J Psychiatry. 2002 Oct;181:348.No abstract.

6866. Glover DA, Poland RE. Urinary cortisol and catecholamines in mothers of child cancer survivors with and without PTSD. Psychoneuroendocrinology. 2002 Oct;27(7):805-19.

Reduced cortisol coupled with elevated catecholamines has been reported for patients with post-traumatic stress disorder (PTSD) precipitated by war and other traumas considered to be "outside the range of usual experiences". It is unclear whether these neuroendocrine abnormalities also occur in PTSD precipitated by more commonly experienced traumas associated with life-threatening illness. Overnight (12-h) urinary cortisol, norepinephrine (NE) and epinephrine (E) were measured in 21 mothers of pediatric cancer survivors with (n = 14) and without PTSD symptoms (n = 7) and in control mothers of healthy children (n = 8). Mothers meeting subthreshold and full PTSD criteria were combined to form the PTSD symptoms group. The PTSD group showed lower total urinary cortisol and a trend for higher total urinary NE than the non-PTSD group, who in turn were no different from controls. There were no significant group effects for E. Cortisol (but not NE) effects remained after controlling for symptoms of co-morbid depression. The finding of reduced cortisol in illness-related PTSD demonstrates neuroendocrine dysregulation similar to that found previously in other types of trauma (e.g., war-related). Future longitudinal studies with repeated urinary collection procedures will be necessary to clarify measurement issues and establish the time course and health implications of the neuroendocrine perturbations. Copyright 2002 Elsevier Science Ltd.

6867. Lemstra M, Stewart B, Olszynski WP. Effectiveness of multidisciplinary intervention in the treatment of migraine: a randomized clinical trial. Headache. 2002 Oct;42(9):845-54.

OBJECTIVE: To test the effectiveness of a multidisciplinary management program for migraine treatment in a group, low cost, nonclinical setting. DESIGN: A prospective, randomized, clinical trial. BACKGROUND: Although numerous studies document the efficacy of pharmacological migraine management, it is unclear whether an effective long-term management approach exists. METHODS: Eighty men and women were randomly assigned to 1 of 2 groups. The intervention group consisted of a neurologist and physical therapist intake and discharge, 18 group-supervised exercise therapy sessions, 2 group stress management and relaxation therapy lectures, 1 group dietary lecture, and 2 massage therapy sessions. The control group consisted of standard care with the patient's family physician. Outcome measures included self-perceived pain intensity, frequency, and duration; functional status; quality of life; health status; depression; prescription and nonprescription medication use; and work status. Outcomes were measured at the end of the 6-week intervention and at a 3-month follow-up. Results.-Forty-one of 44 patients from the intervention group and all 36 patients from the control group completed the study. There were no statistically significant differences between the 2 groups before intervention. Intention to treat analysis revealed that the intervention group experienced statistically significant changes in self-perceived pain frequency (P =.000), pain intensity (P =.001), pain duration (P =.000), functional status (P =.000), quality of life (P =.000), health status (P =.000), pain related disability (P =.000), and depression (P =.000); these differences retained their significance at the 3-month follow-up. There were no statistically significant changes in medication use or work status. CONCLUSIONS: Positive health related outcomes in migraine can be obtained with a low cost, group, multidisciplinary intervention in a community based nonclinical setting.

6868. Lester P, Chesney M, Cooke M, Weiss R, Whalley P, Perez B, Glidden D, Petru A, Dorenbaum A, Wara D. When the time comes to talk about HIV: factors associated with diagnostic disclosure and emotional distress in HIV-infected children. J Acquir Immune Defic Syndr. 2002 Nov 1;31(3):309-17.

OBJECTIVE: To determine factors related to the timing and probability of nondisclosure of HIV status to perinatally HIV-infected children, and to explore factors associated with emotional distress in HIV-infected children. METHODS: This is a cross-sectional study of 51 HIV-infected children based on medical records, parent interviews, and child assessments. RESULTS: 1) Probability of earlier age of disclosure is associated with higher child IQ (p =.04) and more family expressiveness (p =.01); 2) controlling for child age, disclosure status at time of study is associated with major life events, but not with medical status; and 3) factors associated with increased parent-rated anxiety in HIV-infected children in univariate analyses are: HIV disclosure (p =.04), other major life events (p =.001), higher medication dose frequency ( p=.01), and child age (p =.01). Increased depression is associated only with more medication doses (p =.02). CONCLUSION: These data indicate that higher child IQ and greater family expressiveness increase the probability of earlier diagnostic disclosure to HIV-infected children. Factors associated with emotional distress highlight important areas of clinical attention. These data suggest that diagnostic disclosure may not necessarily minimize emotional distress, indicating the need for further evaluation of the appropriate timing and type of disclosure for pediatric HIV.

6869. Mathew JL, Kabi BC, Rath B. Anti-oxidant vitamins and steroid responsive nephrotic syndrome in Indian children. J Paediatr Child Health. 2002 Oct;38(5):450-37.

OBJECTIVE: In recent years, it has been proposed that nephrotic syndrome is a consequence of an imbalance between oxidant and anti-oxidant activity. In the present study, the levels of micronutrient anti-oxidant vitamins (vitamin E, vitamin C, carotene and riboflavin) in Indian children with steroid responsive nephrotic syndrome were investigated. Their levels were measured during the acute proteinuric phase of the disease, as well as during clinical recovery (remission), in order to understand the possible role of nutritionally modifiable anti-oxidants in the aetiopathogenesis of the disease. METHODS: The study was a hospital based, prospective cohort study. Serum and erythrocyte vitamin E, leucocyte vitamin C, serum carotene, erythrocyte riboflavin activity and serum malonyldialdehyde (MDA) levels were measured in 30 consecutive cases of children with nephrotic syndrome (International Study of Kidney Diseases in Children (ISKDC) criteria) during the proteinuric phase of the disease and at 4 weeks after remission was induced by steroid therapy. The same biochemical parameters were measured in healthy siblings (controls) of the 30 patients. RESULTS: Mean vitamin E (serum and erythrocyte), vitamin C and carotene were significantly lower during the proteinuric phase of the disease, and there was decreased erythrocyte riboflavin activity. There was significant elevation in the serum level of MDA during this phase. In addition, all these parameters tended to improve during remission, although complete normalization did not occur. CONCLUSION: These vitamins were active in performing their anti-oxidant function, as indicated by significant depression in their levels during the

acute (proteinuric) phase, followed by partial recovery during remission. It may be concluded that steroid responsive nephrotic syndrome in children is associated with oxidative stress.

6870. Moore B.Cortisol, stress and depression. Br J Psychiatry. 2002 Oct;181:348; author reply 349. No abstract.

6871. Nakano T, Wenner M, Inagaki M, Kugaya A, Akechi T, Matsuoka Y, Sugahara Y, Imoto S, Murakami K, Uchitomi Y.Relationship between distressing cancer-related recollections and hippocampal volume in cancer survivors. Am J Psychiatry. 2002 Dec;159(12):2087-93.

OBJECTIVE: Having cancer is extremely stressful, and distressing cancer-related recollections are frequently reported by cancer survivors. Smaller hippocampal volume has been observed in stress-related neuropsychiatric disorders, such as posttraumatic stress disorder (PTSD) and major depression. The aim of this study was to determine whether there is a similar association between distressing cancer-related recollections and hippocampal volume. METHOD: The subjects were 67 women who had had breast cancer surgery 3 or more years earlier and had no history of PTSD or major depression before the cancer. Each woman was evaluated with a semistructured interview to determine whether she had a history of distressing cancer-related recollections. Hippocampal volume was measured by three-dimensional magnetic resonance imaging, and memory function was assessed by the Wechsler Memory Scale-Revised. RESULTS: The volume of the left hippocampus was significantly smaller (5%) in the subjects with a history of distressing cancer-related recollections (N=28) than in those without any such history (N=39). There was no significant difference in right hippocampal volume or whole brain volume measured as a control. There were no significant differences in delayed memory or percentage retention. However, significantly worse immediate visual memory, but not verbal memory, was observed in the subjects with a history of distressing cancer-related recollections. CONCLUSIONS: Having distressing cancer-related recollections is associated with smaller left hippocampal volume in survivors of breast cancer.

6872. Palinkas A, Toth E, Amyot R, Rigo F, Venneri L, Picano E. The value of ECG and echocardiography during stress testing for identifying systemic endothelial dysfunction and epicardial artery stenosis. Eur Heart J. 2002 Oct;23(20):1587-95.

BACKGROUND: In the stress imaging era, ECG positivity is regarded as a frequent source of false-positive responses. However, it is known that normal coronary arteries frequently coexist with abnormal endothelial function in patients with chest pain. AIM: To evaluate the anatomical coronary epicardial, and functional systemic endothelial determinants of wall motion and electrocardiographic responses during stress testing. METHOD: Sixty-eight in-hospital patients with chest pain syndrome, no previous myocardial infarction, and off nitrate therapy at the time of testing underwent, on different days, in random order and within 1 month: (1) stress ECG echo testing (with dipyridamole in 43, dobutamine in 3, and exercise in 22 patients); (2) coronary angiography; (3) endothelium-dependent, flow-mediated dilation of the brachial artery during reactive hyperaemia using high-resolution ultrasound. Criteria of positivity were: ST segment depression >0.1mm in the stress ECG; regional dysfunction >2 segments demonstrated by stress-echo; diameter reduction >50% on coronary angiography; and <5% flow-mediated dilation as revealed by endothelial function. RESULTS: Significant coronary artery disease was present in 39 patients, and was predicted on multivariate analysis by stress-induced wall motion abnormalities (OR=108.8; 95% CI=8.5-1,389.4, P=0.0003), but not by either ST segment depression (P=0.13; OR=0.47; 95% CI=0.7-1.3) or reduced flow-mediated dilation (P=0.81; OR=0.87; 95% CI=0.27-2.8). Abnormal flow-mediated dilation was present in 53 patients (78%), and was predicted by stress-induced ST segment depression (P=0.023; OR=6.2; 95% CI=1.3-30.5), but not by either stress echo positivity (P=0.66; OR=0.77; 95% CI=0.23 to 2.5) or angiographically assessed coronary artery disease. There was no correlation between flow-mediated dilation and extent of coronary artery disease as assessed by the angiographic Duke score (from 0=normal to 100=most severe disease): r=-0.13, P=0.91. CONCLUSION: Epicardial coronary artery anatomy affects wall motion abnormalities, and systemic endothelial dysfunction affects ST segment depression during stress. However, echocardiographic positivity is unrelated to endothelial dysfunction, and electrocardiographic positivity is an inaccurate predictor of coronary stenosis. An integration of ECG and functional markers is warranted in the stress testing lab.

6873. Pine DS.Treating children and adolescents with selective serotonin reuptake inhibitors: how long is appropriate? J Child Adolesc Psychopharmacol. 2002 Fall;12(3):189-203. Review.

This article addresses a key question on the use of selective serotonin reuptake inhibitors (SSRIs) among children and adolescents. As briefly reviewed, recent randomized controlled trials have established the safety and efficacy of SSRIs in the acute treatment of major depression and anxiety disorders among children and adolescents. Major questions emerge in light of these data concerning the potential risks and benefits of long-term SSRI use among children and adolescents who receive significant short-term benefits from SSRI treatment. The current review summarizes research on longitudinal outcomes, neuroscience, and psychopharmacology to formulate a set of preliminary recommendations on long-term SSRI use. A review of data in these areas supports three conclusions. First, for children who achieve marked reduction in anxiety or depressive symptoms on an SSRI, clinicians should consider recommending a medication-free trial. Second, when indicated, this medication-free trial should coincide with the first low-stress period occurring after 1 year of continual SSRI treatment. Third, SSRI treatment should be reinitiated in children who exhibit signs of relapse during this medication-free trial.

6874. Scott LV, Dinan TG.Vasopressin as a target for antidepressant development: an assessment of the available evidence. J Affect Disord. 2002 Nov;72(2):113-24.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30-50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary-adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.

6875. Skari H, Skreden M, Malt UF, Dalholt M, Ostensen AB, Egeland T, Emblem R. Comparative levels of psychological distress, stress symptoms, depression and anxiety after childbirth--a prospective population-based study of mothers and fathers.BJOG. 2002 Oct;109(10):1154-63.

OBJECTIVE: To compare maternal and paternal psychological responses following birth of a healthy baby; and to explore predictors of parental psychological distress. DESIGN: A prospective, longitudinal, population-based cohort study. SETTING: A Norwegian district general hospital. POPULATION: One hundred and twenty-seven mothers and 122 fathers were included. METHODS: Eligible consenting parents were enrolled. The assessments, which were performed zero to four days after birth, at six weeks and at six months, included General Health Questionnaire-28 (GHQ-28), State Anxiety Inventory and Impact of Event Scale. The response rates at the three occasions were 97%, 85% and 71%. MAIN OUTCOME MEASURES: Symptoms of intrusion, avoidance, arousal and psychological distress including anxiety, depression, social dysfunction and somatisation. RESULTS: Clinically important psychological distress was reported by 37% of the mothers and 13% of the fathers a few days after childbirth (P < 0.001). Severe intrusive stress symptoms were reported by 9% and 2% of mothers and fathers, respectively (P = 0.002). Level of intrusive stress was the outcome that differed most clearly between mothers and fathers at all three points of time. Being a single parent, multiparity and a previous traumatic birth were significant independent predictors of acute maternal psychological distress. After six weeks and six months, the level of psychological distress including symptoms of depression fell to levels found in the general population. CONCLUSIONS: Childbirth does not seem to trigger long term psychological distress in most parents. Clinically important psychological distress occurred more frequently in mothers than in fathers. Acute maternal psychological distress was predicted by being a single parent, being multiparous, and having a previous traumatic birth.

6876. Strike PC, Steptoe A. Depression, stress, and the heart. Heart. 2002 Nov;88(5):441-3. No abstract

6877. Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, Brummer M, Staib L, Vermetten E, Charney DS, Nemeroff CB, Bremner JD.Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry. 2002 Dec;159(12):2072-80.

OBJECTIVE: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects. METHOD: Study participants were 32 women with current unipolar major depressive disorder-21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse-and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects' diagnoses. RESULTS: The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects. CONCLUSIONS: A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.

6878. Weinreb L, Wehler C, Perloff J, Scott R, Hosmer D, Sagor L, Gundersen C. Hunger: its impact on children's health and mental health. Pediatrics. 2002 Oct;110(4):e41.

OBJECTIVE: Hunger, with its adverse consequences for children, continues to be an important national problem. Previous studies that document the deleterious effects of hunger among children cannot distinguish child from family hunger and do not take into account some critical environmental, maternal, and child variables that may influence child outcomes. This study examines the independent contribution of child hunger on children's physical and mental health and academic functioning, when controlling for a range of environmental, maternal, and child factors that have also been associated with poor outcomes among children. METHODS: With the use of standardized tools, comprehensive demographic, psychosocial, and health data were collected in Worcester, Massachusetts, from homeless and low-income housed mothers and their children (180 preschool-aged children and 228 school-aged children). Mothers and children were part of a larger unmatched case-control study of homelessness among female-headed households. Hunger was measured by a set of 7 dichotomous items, each asking the mother whether she has or her children have experienced a particular aspect of hunger during the past year--1 concerns food insecurity for the entire family, 2 concern adult hunger, and 4 involve child hunger. The items, taken from the Childhood Hunger Identification Project measure, are summed to classify the family and divided into 3 categories: no hunger, adult or moderate child hunger, or severe child hunger (indicating multiple signs of child hunger). Outcome measures included children's chronic health condition count using questions adapted from the National Health Interview Survey, Child Health Supplement, and internalizing behavior problems and anxiety/depression, measured by the Child Behavior Checklist. Additional covariates included demographic variables (ie, age, gender, ethnicity, housing status, number of moves, family size, income), low birth weight, child life events (ie, care and protection order, out of home placement, abuse, severe life events count), developmental problems (ie, developmental delay, learning disability, emotional problems), and mother's distress and psychiatric illness. Multivariate regression analyses examined the effect of child hunger on physical and mental health outcomes. RESULTS: The average family size for both preschoolers and school-aged children was 3; about one third of both groups were white and 40% Puerto Rican. The average income of families was approximately $11 000. Among the school-aged children, on average 10 years old, 50% experienced moderate child hunger and 16% severe child hunger. Compared with those with no hunger, school-aged children with severe hunger were more likely to be homeless (56% vs 29%), have low birth weights (23% vs 6%), and have more stressful life events (9 vs 6) when compared with those with no hunger. School-aged children with severe hunger scores had parent-reported anxiety scores that were more than double the scores for children with no hunger and significantly higher chronic illness counts (3.4 vs 1.8) and internalizing behavior problems when compared with children with no hunger. There was no relationship between hunger and academic achievement. Among preschool-aged children, who averaged 4 years of age, 51% experienced moderate child hunger and 8% severe child hunger. For preschoolers, compared with children with no hunger, severe hunger was associated with homelessness (75% vs 48%), more traumatic life events (8.5 vs 6), low birth weight (23% vs 6%), and higher levels of chronic illness and internalizing behavior problems. Mothers of both preschoolers and school-aged children who reported severe hunger were more likely to have a lifetime diagnosis of posttraumatic stress disorder. For school-aged children, severe hunger was a significant predictor of chronic illness after controlling for housing status, other's distress, low birth weight, and child live events. For preschoolers, moderate hunger was a significant predictor of health conditions while controlling for potenns while controlling for potential explanatory factors. For both preschoolers and school-aged children, severe child hunger was associated with higher levels of internalizing behavior problems. After controlling for housing status, mother's distress, and stressful life events, severe child hunger was also associated with higher reported anxiety/depression among school-aged children. CONCLUSION: This study goes beyond previous research and highlights the independent relationship between severe child hunger and adverse physical health and mental health outcomes among low-income children. Study findings underscore the importance of clinical recognition of child hunger and its outcomes, allowing for preventive interventions and efforts to increase access to food-related resources for families.

Heart Disease:

6879. Dahan M, Viron BM, Poiseau E, Kolta AM, Aubry N, Paillole C, Pessione F, Bonnin F, Logeart D, Gourgon R, Mignon FE.Combined dipyridamole-exercise stress echocardiography for detection of myocardial ischemia in hemodialysis patients: an alternative to stress nuclear imaging. Am J Kidney Dis. 2002 Oct;40(4):737-44.

BACKGROUND: Stress nuclear imaging is the noninvasive technique currently used to detect coronary artery disease (CAD) in dialysis patients. Stress echocardiography is recognized as an alternative to stress nuclear imaging for the general population. The aim of this study is to assess the diagnostic accuracy of stress echocardiography for detecting myocardial ischemia in hemodialysis patients. METHODS: Stress echocardiography and stress technetium-99m-tetrofosmin (Myoview; Amersham International Plc) imaging were performed simultaneously for 66 asymptomatic hemodialysis patients in a single session, using a combination of high-dose dipyridamole and symptom-limited exercise. Coronary angiography was performed in 44 patients with at least one abnormal noninvasive test result or who were considered high-risk despite normal noninvasive test results. RESULTS: Results for stress echocardiography were abnormal in 15 patients (22%); stress Myoview, in 14 patients (21%); and coronary angiography, in 12 patients (18%). The sensitivity of stress echocardiography for detecting myocardial ischemia (defined as stress Myoview defect) was 86%; specificity, 94%; positive predictive value, 80%; negative predictive value, 96%; and overall accuracy, 92%. The sensitivity of stress echocardiography for detecting CAD (defined as abnormal coronary angiography result) was 83%; specificity, 84%; positive predictive value, 67%; negative predictive value, 93%; and overall accuracy, 84%. Stress echocardiography and stress Myoview did not differ significantly in overall accuracy for detecting CAD (84% versus 91%; P = not significant). CONCLUSION: In hemodialysis patients, combined dipyridamole-exercise echocardiography is an accurate method to detect both myocardial ischemia and CAD and represents an alternative to stress nuclear imaging. Copyright 2002 by the National Kidney Foundation, Inc.

6880. Das UN. Is insulin an endogenous cardioprotector? Crit Care. 2002 Oct;6(5):389-93.

Stress hyperglycemia and diabetes mellitus with myocardial infarction are associated with increased risk for in-hospital mortality, congestive heart failure, or cardiogenic shock. Hyperglycemia triggers free radical generation and suppresses endothelial nitric oxide generation, and thus initiates and perpetuates inflammation. Conversely, insulin suppresses production of tumor necrosis factor-alpha and free radicals, enhances endothelial nitric oxide generation, and improves myocardial function. It is proposed that the balance between insulin and plasma glucose levels is critical to recovery and/or complications that occur following acute myocardial infarction and in the critically ill. Adequate attention should be given to maintaining euglycemia (plasma glucose <or= 110 mg/dl) in order to reduce infarct size and improve cardiac function while using a glucose-insulin-potassium cocktail.

6881. Elhendy A, Bax JJ, Poldermans D. Dobutamine stress myocardial perfusion imaging in coronary artery disease.J Nucl Med. 2002 Dec;43(12):1634-46.

The accurate noninvasive diagnosis and functional evaluation of coronary artery disease is an important step in selecting the appropriate management strategy. Dobutamine stress myocardial perfusion imaging is an alternative to exercise in patients with limited exercise capacity. In many centers, the test is performed on patients who have a contraindication for vasodilator stress testing. Recent studies have shown hyperemia induced by the standard dobutamine-atropine stress test is not less than hyperemia induced by dipyridamole. The feasibility of the test is 90% and is often higher in patients without beta-blocker therapy. The safety of the test has been well studied and was also demonstrated in specific patients groups, such as patients with left ventricular dysfunction, the elderly, and heart transplant recipients. The diagnostic accuracy has been demonstrated in patients with and without myocardial infarction and in specific groups such as those with hypertension, left ventricular hypertrophy, and heart transplant recipients and after revascularization. The technique has a high sensitivity for prediction of functional recovery in patients with myocardial dysfunction referred for revascularization. The presence and severity of myocardial perfusion abnormalities assessed by this method are powerful predictors of cardiac events, incremental to clinical data. This article describes the methodology, safety, feasibility, diagnostic accuracy, and prognostic value of dobutamine stress myocardial perfusion imaging in patients with known or suspected coronary artery disease, with additional considerations for the application of the test in specific patient groups.

6882. Fesmire FM, Hughes AD, Fody EP, Jackson AP, Fesmire CE, Gilbert MA, Stout PK, Wojcik JF, Wharton DR, Creel JH. The Erlanger chest pain evaluation protocol: a one-year experience with serial 12-lead ECG monitoring, two-hour delta serum marker measurements, and selective nuclear stress testing to identify and exclude acute coronary syndromes. Ann Emerg Med. 2002 Dec;40(6):584-94.

STUDY OBJECTIVE: We determine the overall use of a 6-step accelerated chest pain protocol to identify and exclude acute coronary syndrome (ACS) and to confirm previous findings of the use of serial 12-lead ECG monitoring (SECG) in conjunction with 2-hour delta serum marker measurements to identify and exclude acute myocardial infarction (AMI). METHODS: A prospective observational study was conducted over a 1-year period from January 1, 1999, through December 31, 1999, in 2,074 consecutive patients with chest pain who underwent our accelerated evaluation protocol, which includes 2-hour delta serum marker determinations in conjunction with automated SECG for the early identification and exclusion of AMI and selective nuclear stress testing for identification and exclusion of ACS. In patients not undergoing emergency reperfusion therapy, physician judgment was used to determine patient disposition at the completion of the 2-hour evaluation period: admit for ACS, discharge or admit for non-ACS condition, or immediate emergency department nuclear stress scan for possible ACS. A positive protocol was defined as a positive result in 1 or more of the 6 incremental steps in our chest pain evaluation protocol: (1) initial ECG diagnostic of acute injury or reciprocal injury; (2) baseline creatine kinase (CK)-MB level of 10 ng/mL or greater and index of 5% or greater or cardiac troponin I level of 2 ng/mL or greater; (3) new/evolving injury or new/evolving ischemia on SECG; (4) increase in CK-MB level of +1.5 ng/mL or greater or cardiac troponin I level of +0.2 ng/mL or greater in 2 hours; (5) clinical diagnosis of ACS despite a negative 2-hour evaluation; and (6) reversible perfusion defect on stress scan compared with on resting scan. All patients were followed up for 30-day ACS, which was defined as myocardial infarction (MI), percutaneous coronary intervention/coronary artery bypass grafting, coronary arteriography revealing stenosis of major coronary artery of 70% or greater not amenable to percutaneous coronary intervention/coronary artery bypass grafting, life-threatening complication, or cardiac death within 30 days of ED presentation. RESULTS: Discharge diagnosis in the 2,074 study patients consisted of 179 (8.6%) patients with AMI, 26 (1.3%) patients with recent AMI (decreasing curve of CK-MB), and 327 (15.8%) patients with 30-day ACS. At 2 hours, sensitivity and specificity for MI (AMI or recent AMI) of SECG plus delta serum marker measurements was 93.2% and 93.9%, respectively (positive likelihood ratio 15.3; negative likelihood ratio 0.07). At the completion of the full ED evaluation protocol (positive result in >or=1 of the 6 incremental steps), sensitivity and specificity for 30-day ACS was 99.1% and 87.4%, respectively (positive likelihood ratio 7.9; negative likelihood ratio 0.01). CONCLUSION: An accelerated chest pain evaluation strategy consisting of SECG, 2-hour delta serum marker measurements, and selective nuclear stress testing in conjunction with physician judgment identifies and excludes MI and 30-day ACS during the initial evaluation of patients with chest pain.

6883. Freese R, Alfthan G, Jauhiainen M, Basu S, Erlund I, Salminen I, Aro A, Mutanen M. High intakes of vegetables, berries, and apples combined with a high intake of linoleic or oleic acid only slightly affect markers of lipid peroxidation and lipoprotein metabolism in healthy subjects. Am J Clin Nutr.2002 Nov;76(5):950-60.

BACKGROUND: A high consumption of vegetables and fruit is associated with decreased risk of ischemic heart disease and several cancers. The pathophysiology of these diseases involves free radical mechanisms. Diet may either enhance or diminish oxidative stress in the body. OBJECTIVE: We studied the effects of high and low intakes of vegetables, berries, and apples on markers of lipid peroxidation and lipoprotein metabolism in subjects consuming diets high in linoleic or oleic acid. DESIGN: For 6 wk, healthy men and women (n = 77; aged 19-52 y) consumed 1 of 4 controlled isoenergetic diets rich in either linoleic acid (11% of energy) or oleic acid (12% of energy) and containing either 815 or 170 g vegetables, berries, and apples/10 MJ. Nineteen healthy volunteers served as control subjects. Several markers of dietary compliance (plasma fatty acids, vitamin C, carotenoids, and quercetin), lipid peroxidation [ex vivo LDL oxidation, plasma and LDL thiobarbituric acid-reactive substances, paraoxonase (EC 3.1.8.1), and urinary 8-iso-prostaglandin F(2)(alpha)], and lipoprotein metabolism (plasma lipids, apolipoproteins, and lipid transfer protein activities) were measured from samples collected before and at the end of the experimental period. RESULTS: Plasma fatty acid composition and antioxidant concentrations showed that compliance with the diets was good. However, there were no significant differences between the diets in the markers of lipid peroxidation and lipoprotein metabolism. CONCLUSIONS: In healthy volunteers with adequate vitamin intakes, 6-wk diets differing markedly in the amounts of linoleic and oleic acid and vegetables, berries, and apples did not differ in their effects on lipid peroxidation or lipoprotein metabolism.

6884. Gerber AM, Oosthuizen GM, Crous A.A possible link between melatonin levels, stress and coronary heart disease.S Afr Med J.2002 Oct;92(10):794-5.No abstract.

6885. Guazzi M, Brambilla R, De Vita S, Guazzi MD.Diabetes worsens pulmonary diffusion in heart failure, and insulin counteracts this effect.Am J Respir Crit Care Med. 2002 Oct 1;166(7):978-82.

Chronic heart failure (CHF) (hydrostatic stress) and diabetes (basal laminae thickening) share the potentiality of damaging the alveolar-capillary membrane. We investigated 15 control subjects and 3 groups of 15 patients each having type 2 diabetes (Group 1), CHF (Group 2), and diabetes and CHF (Group 3), to probe whether addition of diabetes worsens lung diffusion in CHF and whether insulin counteracts this effect. Compared with control subjects, carbon monoxide diffusing capacity (DL(CO)) and diffusing capacity of the alveolar-capillary membrane at rest were increasingly depressed from Group 1 through Group 3. DL(CO) was lower than predicted in 11 patients each in Groups 1 and 2 and in all patients in Group 3. Regular insulin (10 IU) was ineffective in CHF alone, whereas it improved DL(CO) and diffusing capacity of the alveolar-capillary membrane in diabetes; changes, however, were significantly greater in the patients with both diabetes and CHF (+17.6%, +27.3%) than in those with diabetes alone (+9.2%, +13.1%). Insulin did not affect lung spirometry, volumes, and hemodynamics. Thus, gas transfer is depressed in a number of patients with diabetes or CHF; comorbidity increases the frequency and extent of this disorder. Insulin facilitates diffusion in diabetes, through an influence on alveolar-capillary conductance, and its efficacy is greater in comorbidity; diabetes is more disturbing in patients with CHF and produces a synergistic rather than a simple additive effect.

6886. Heidenreich PA.The search for myocardial viability: do Q waves help? Am Heart J. 2002 Nov;144(5):745-6. No abstract.

6887. Kalra DK, Ramchandani M, Zhu X, Lawrie G, Reardon MJ, Mann DL, Zoghbi WA, Nagueh SF.Relation of tissue Doppler-derived myocardial velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase in patients with ischemic cardiomyopathy having coronary artery bypass grafting.Am J Cardiol. 2002 Oct 1;90(7):708-12

We evaluated the relation of segmental and annular tissue Doppler (TD) velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide (NOS2) in humans. Seven patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsies (2 biopsies per patient for a total of 14 specimens) at the time of bypass surgery. The specimens were analyzed for the number of mRNA copies of TNF-alpha and NOS2. In addition, serum levels of TNF-alpha and nitrite were determined before and after surgery. Normal segments (n = 7) had fewer numbers of mRNA copies of both TNF-alpha (54.6 vs 6.5, p = 0.002) and NOS2 (3,093 +/- 486 vs 661 +/- 259, p <0.001) than dysfunctional segments (n = 7). Peak systolic velocity (Sm) (13.3 +/- 1.4 vs 4.9 +/- 1.6 cm/s, p = 0.002) and early diastolic velocity (Em) (16.5 +/- 2.7 vs 8.8 +/- 1.3 cm/s, p = 0.02) were significantly higher in normal segments. A significant correlation was present among Em, Sm, and the number of mRNA copies of TNF-alpha and NOS2 at baseline and during infusion of dobutamine (r range -0.72 to -0.92, p <0.01 for all). Likewise, significant relations were present between the changes in serum cytokine levels and changes in the mitral annulus diastolic velocity, E/Ea ratio, and end-diastolic wall stress (r range 0.75 to 0.88, p </=0.05 for all). In conclusion, Sm and Em are strongly dependent on the regional levels of cytokine gene expression, which are known to have negative inotropic and lusitropic effects when overexpressed.

6888. Karnath BM. Preoperative cardiac risk assessment. Am Fam Physician. 2002 Nov 15;66(10):1889-96.

Heart disease is the leading cause of mortality in the United States. An important subset of heart disease is perioperative myocardial infarction, which affects approximately 50,000 persons each year. The American College of Cardiology (ACC) and American Heart Association (AHA) have coauthored a guideline on preoperative cardiac risk assessment, as has the American College of Physicians (ACP). The ACC/AHA guideline uses major, intermediate, and minor clinical predictors to stratify patients into different cardiac risk categories. Patients with poor functional status or those undergoing high-risk surgery require further risk stratification via cardiac stress testing. The ACP guideline also starts by screening patients for clinical variables that predict perioperative cardiac complications. However, the ACP did not feel there was enough evidence to support poor functional status as a significant predictor of increased risk. High-risk patients would sometimes merit preoperative cardiac catheterization by the ACC/AHA guideline, while the ACP version would reserve catheterization only for those who were candidates for cardiac revascularizationindependent of their noncardiac surgery. A recent development in prophylaxis of surgery-related cardiac complications is the use of beta blockers perioperatively for patients with cardiac risk factors.

6889. Landmesser U, Spiekermann S, Dikalov S, Tatge H, Wilke R, Kohler C, Harrison DG, Hornig B, Drexler H. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation. 2002 Dec 10;106(24):3073-8.

BACKGROUND: Impaired flow-dependent, endothelium-mediated vasodilation (FDD) in patients with chronic heart failure (CHF) results, at least in part, from accelerated degradation of nitric oxide by oxygen radicals. The mechanisms leading to increased vascular radical formation, however, remain unclear. Therefore, we determined endothelium-bound activities of extracellular superoxide dismutase (ecSOD), a major vascular antioxidant enzyme, and xanthine-oxidase, a potent radical producing enzyme, and their relation to FDD in patients with CHF. METHODS AND RESULTS: ecSOD and xanthine-oxidase activities, released from endothelium into plasma by heparin bolus injection, were determined in 14 patients with CHF and 10 control subjects. FDD of the radial artery was measured using high-resolution ultrasound and was assessed before and after administration of the antioxidant vitamin C (25 mg/min; IA). In patients with CHF, endothelium-bound ecSOD activity was substantially reduced (5.0+/-0.7 versus 14.4+/-2.6 U x mL(-1) x min(-1); P<0.01) and closely related to FDD (r=0.61). Endothelium-bound xanthine-oxidase activity was increased by >200% (38+/-10 versus 12+/-4 nmol O2*- x microL(-1); P<0.05) and inversely related to FDD (r=-0.35) in patients with CHF. In patients with low ecSOD and high xanthine-oxidase activity, a greater benefit of vitamin C on FDD was observed, ie, the portion of FDD inhibited by radicals correlated negatively with ecSOD (r=-0.71) but positively with xanthine-oxidase (r=0.75). CONCLUSIONS: These results demonstrate that both increased xanthine-oxidase and reduced ecSOD activity are closely associated with increased vascular oxidative stress in patients with CHF. This loss of vascular oxidative balance likely represents a novel mechanism contributing to endothelial dysfunction in CHF.

6890. Lee SY, Lee CY, Kim HJ, Lee HH, Gwon HC, Kim DK. Stress-induced cardiomyopathy presenting as acute myocardial infarction. Yonsei Med J. 2002 Oct;43(5):670-4.

Stress-induced cardiomyopathy is described as an acute cardiomyopathy that occurs under the influence of an excessive level of catecholamine related to intense emotional stress. A 64-year-old woman presented with symptoms of acute myocardial infarction after emotional upset, but her coronary angiographic findings were revealed to be normal. Diffuse T wave inversions were observed in her electrocardiograms with akinetic wall motions sparing the basal segments in her left ventriculography. After four months, her electrocardiogram and echocardiogram findings had completely returned to normal. The precise diagnosis of this acute cardiomyopathy must be emphasized because it can initially be misdiagnosed as acute coronary syndromes. However in complete contrast to acute myocardial infarction, it has a rapid and favorable recovery with hardly any sequelae after a few months.

6891. Melenovsky V, Malik J, Wichterle D, Simek J, Pisarikova A, Skrha J, Poledne R, Stavek P, Ceska R.Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia.Am Heart J. 2002 Oct;144(4):E6.

BACKGROUND: Combined hyperlipidemia (CH) is an increasingly prevalent risk factor for premature heart disease, and its treatment is troublesome. The aim of this study was to compare the effects of atorvastatin and fenofibrate on nonlipid biochemical risk factors and the low-density lipoprotein (LDL) particle size in subjects with CH. METHODS: Twenty-nine middle-aged men with CH were randomly assigned to open-label therapy with atorvastatin (10 mg daily) or micronized fenofibrate (200 mg daily); they were sequentially treated with both drugs, with crossover of medication after 10 weeks. RESULTS: Atorvastatin was more efficient in the reduction of total cholesterol, whereas fenofibrate was more efficient in the reduction of triglycerides. Only atorvastatin led to a significant reduction of LDL cholesterol and apolipoprotein B. Only fenofibrate increased high-density lipoprotein cholesterol. Neither drug influenced lipoprotein(a). Mean LDL particle size increased both after fenofibrate (3.08%) and atorvastatin (1.77%). Fenofibrate increased serum homocysteine (HCY) by 36.5%. Atorvastatin had no effect on HCY. Only atorvastatin increased fibrinogen by 17.4%. Only fenofibrate reduced C-reactive protein by 51.7%. Neither drug influenced HOMA (homeostasis model assessment) index of insulin resistance. The plasma level of thiobarbituric acid reactive substances, an index of oxidative stress, decreased after both treatments. CONCLUSIONS: Both atorvastatin and fenofibrate had similar beneficial effects on LDL particle size and on oxidative stress. The effects of both drugs on other parameters such as triglycerides, total and high-density lipoprotein cholesterol, fibrinogen, or HCY differed significantly. These differences, together with the risk profile of a patient, should be considered during selection of a particular lipid-lowering modality.

6892. Mohan JC, Patel AR, Passey R, Gupta D, Kumar M, Arora R, Pandian NG.Is the mitral valve area flow-dependent in mitral stenosis? A dobutamine stress echocardiographic study. J Am Coll Cardiol. 2002 Nov 20;40(10):1809-15.

OBJECTIVES: The purpose of this study was to compare the effect of changes in flow rate on the mitral valve area (MVA) derived from two-dimensional echocardiographic planimetry and Doppler pressure half-time (PHT) methods in patients with mitral stenosis (MS). BACKGROUND: Dobutamine stress echocardiography has been proposed as a means of assessing the severity of MS. However, data regarding the effect of an increase in flow rate on MVA are limited. If MVA is indeed flow-dependent, this has important implications for the assessment of the severity of MS, particularly in the setting of reduced cardiac output (CO). METHODS: Dobutamine echocardiography was performed in 57 patients with isolated MS who were in sinus rhythm. The MVA was determined by planimetry and Doppler PHT methods. RESULTS: Cardiac output increased by > or =50% in 27 patients (group I) and by <50% in 30 patients (group II). In group I, the MVA by planimetry increased by only 10.6 +/- 2% and the MVA by PHT increased by 21.9 +/- 4.8%. These changes were similar to those observed in group II (10.7 +/- 3% and 14.8 +/- 4%, respectively; p = NS), despite a much smaller increase in CO. A clinically important change (from the severe to mild category) occurred in only one patient when using the PHT method and in none by planimetry. CONCLUSIONS: Changes in flow rate result in small but clinically insignificant changes in echocardiographic MVA measurement. These methods provide an accurate assessment of MS severity in a majority of patients, independent of changes in flow rate.

6893. Nguyen VH, McLaughlin MA. Coronary artery disease in women: a review of emerging cardiovascular risk factors. Mt Sinai J Med. 2002 Oct;69(5):338-49.

Coronary heart disease is the leading cause of death and disability in both men and women in industrial nations. From 1988 to 1998, the death rate from coronary heart disease actually declined 26.3%, resulting to some extent from the recognition and treatment of modifiable risk factors. The clinical observation that traditional risk factors for atherosclerosis cannot account for all patients who develop coronary heart disease or stroke has stimulated interest in reevaluating these factors and considering other determinants of pathogenesis. Our understanding of atherogenesis has evolved from a focus on lipid deposition within the arterial wall causing obstruction to the broader view of an inflammatory process which involves specific cellular and molecular responses to endothelial dysfunction. As a consequence, emerging cardiovascular risk factors and preventive strategies have been proposed. For example, there is an increasing understanding of the pathology of hypercholesterolemia and the benefits of lipid-lowering medications (specifically statins), the role of oxidative stress, and antioxidant, homocysteine, and hypercoagulable states. This review examines the data for these and other emerging risk factors, with specific attention to gender differences.

6894. Picano E, Alaimo A, Chubuchny V, Plonska E, Baldo V, Baldini U, Pauletti M, Perticucci R, Fonseca L, Villarraga HR, Emanuelli C, Miracapillo G, Hoffmann E, De Nes M.Noninvasive pacemaker stress echocardiography for diagnosis of coronary artery disease: a multicenter study. J Am Coll Cardiol. 2002 Oct 2;40(7):1305-10.

OBJECTIVE: We evaluated the feasibility, safety, and diagnostic accuracy of noninvasive pacemaker stress echocardiography (PASE) test as a potential alternative to exercise or pharmacologic stress in patients with suspected or known coronary artery disease (CAD). BACKGROUND: Transesophageal atrial pacing echocardiography is an accurate test for detection of CAD, but its practical impact has been blunted by semi-invasiveness. In the expanding population of patients with permanent pacemakers (PMs), a pacing stress test can be administered noninvasively by external programming of the PM. METHODS: In a prospective, multicenter, international study design, transthoracic stress-pacing echocardiography was performed in 46 consecutive patients with a permanent PM (33 men, 13 women; age 66.6 +/- 11.1 years) with suspected or known CAD. All patients underwent noninvasive PM-stress test by external programming (10 beats/min increments up to ischemia or target heart rate). Coronary angiography was performed in all patients independently of test results. Significant CAD was defined as >/=50% visually assessed diameter reduction in at least one major epicardial coronary artery. All coronary angiograms were scored by Duke prognostic weight values. RESULTS: Fifteen patients were stimulated in atrial, and the remaining 31 in ventricular mode during stress. No significant side effects were observed. Echocardiographic images were interpretable in all patients. The average duration of stress was 8.9 +/- 3.5 min. Significant CAD was found in 27 patients. Sensitivity of PASE for identifying patients with significant CAD was 70%, specificity was 90%, and accuracy was 78%. When any abnormal wall motion at rest that remained unchanged at peak stress was regarded as a positive result of PASE, then the sensitivity, specificity, and accuracy levels for identifying patients with significant CAD were 85%, 84%, and 85%, respectively. Four of the eight patients with a false negative did not reach the target heart rate. The Duke values had significant correlation with values of wall motion score index at peak stress (r = 0.67) and with peak heart rate (r = -0.3). CONCLUSIONS: Noninvasive PASE is a simple, rapid, safe, and diagnostically efficient option for patients with permanent PM and suspected or known CAD.

6895. Postma AV, Denjoy I, Hoorntje TM, Lupoglazoff JM, Da Costa A, Sebillon P,Mannens MM, Wilde AA, Guicheney P. Absence of calsequestrin 2 causes severe forms of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2002 Oct 18;91(8):e21-6.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by syncopal events and sudden cardiac death at a young age during physical stress or emotion, in the absence of structural heart disease. We report the first nonsense mutations in the cardiac calsequestrin gene, CASQ2, in three CPVT families. The three mutations, a nonsense R33X, a splicing 532+1 G>A, and a 1-bp deletion, 62delA, are thought to induce premature stop codons. Two patients who experienced syncopes before the age of 7 years were homozygous carriers, suggesting a complete absence of calsequestrin 2. One patient was heterozygous for the stop codon and experienced syncopes from the age of 11 years. Despite the different mutations, there is little phenotypic variation of CPVT for the CASQ2 mutations. Of the 16 heterozygous carriers of these various mutations, 14 were devoid of clinical symptoms or ECG anomalies, whereas 2 of them had ventricular arrhythmias at ECG on exercise tests. In line with this, the diagnosis of the probands was difficult because of the absence of a positive family history. In conclusion, these additional three CASQ2 CPVT families suggest that CASQ2 mutations are more common than previously thought and produce a severe form of CPVT. The full text of this article is available at http://www.circresaha.org.

6896. Preda I. Differentiation between endothelial dysfunction and epicardial coronary artery stenosis with the aid of stress ECG and echocardiography. A novel return of the old ECG! Eur Heart J. 2002 Oct;23(20):1561-2. No abstract.

6897. Schinkel AF, Bax JJ, Boersma E, Elhendy A, Vourvouri EC, Roelandt JR, Poldermans D. Assessment of residual myocardial viability in regions with chronic electrocardiographic Q-wave infarction.Am Heart J. 2002 Nov;144(5):865-9.

BACKGROUND: Q waves on the electrocardiogram are often considered to be reflective of irreversibly scarred myocardium due to antecedent transmural myocardial infarction. However, there are some indications that residual viable tissue may be present in Q-wave-infarcted regions. It is clinically relevant to know how many Q-wave regions contain viable tissue because these patients may benefit from revascularization in terms of improvement of function and long-term survival. METHODS: Patients (n = 150) with chronic electrocardiographic Q-wave infarction, heart failure symptoms, and chronic coronary artery disease underwent dobutamine-atropine stress echocardiography to assess myocardial viability. Residual viability in regions with Q-wave infarction was considered present when the end-diastolic wall thickness (EDWT) was >6 mm and the response during dobutamine infusion indicated viable tissue. RESULTS: Baseline echocardiography revealed 517 dysfunctional myocardial regions; 202 of the dysfunctional regions were related to Q waves on the electrocardiogram and the other 315 dysfunctional regions were not. EDWT was < or =6 mm in 13 regions with a Q wave on the electrocardiogram, with only 1 region exhibiting viable tissue during dobutamine stress echocardiography. EDWT was >6 mm in 189 regions with a Q wave, with 118 (62%) having viable tissue on dobutamine stress echocardiography. In 6 dysfunctional regions without a Q wave, EDWT was < or =6 mm, with all being nonviable on dobutamine stress echocardiography; of the 309 regions without a Q wave and EDWT >6 mm, 204 (66%) exhibited viability on dobutamine stress echocardiography. CONCLUSIONS: Fifty-eight percent of dysfunctional regions related to chronic Q waves were viable according to the combined information of EDWT and dobutamine stress echocardiography. EDWT </=6 mm virtually excludes viability; regions with EDWT >6 mm need additional testing to detect or exclude viability.

6898. Yetkin E, Senen K, Ileri M, Atak R, Battaoglu B, Yetkin O, Tandogan I, Turhan H, Cehreli S. Identification of viable myocardium in patients with chronic coronary artery disease and myocardial dysfunction: comparison of low-dose dobutamine stress echocardiography and echocardiography during glucose-insulin-potassium infusion. Angiology. 2002 Nov-Dec;53(6):671-6.

Low-dose dobutamine stress echocardiography (LDDSE) is one of the methods most used to assess myocardial viability. Glucose-insulin-potassium (GIK) has been shown to increase contraction of the ischemic zone. The aim of this study was to compare LDDSE and echocardiography during GIK infusion for detection of myocardial viability in patients with chronic coronary artery disease (CAD) and myocardial dysfunction. Twenty-one patients who had chronic CAD and myocardial dysfunction were included in the study. Glucose-insulin-potassium protocol consisted of a fixed dose of insulin (100 microU/kg/hour IV) and a variable glucose/potassium infusion rate. GIK echocardiography was made at baseline and after 60 minutes of GIK infusion. During continuous electrocardiographic, blood pressure, and echocardiographic monitoring, an intravenous infusion of dobutamine (3 microg/kg body weight/min) was started with an infusion pump and continued for 5 minutes and then increased to 5 microg/kg/min and 10 microg/kg/min for another 5 minutes. The detected viable myocardium was defined as 1 or 2 scores decreasing in at least 2 adjacent abnormal segments during LDDSE and GIK echocardiography. Viability was detected in 19% (52 segments) of the asynergic segments at baseline with GIK echocardiography and 16% (44 segments) of those segments with LDDSE (p>0.05). Left ventricular wall motion score index at baseline was 2.24+/-0.35 and it decreased significantly during both LDDSE (p=0.004 vs 2.11+/-0.36) and GIK echocardiography (p=0.001 vs 2 .09+/-0.32). The agreement between LDDSE and GIK echocardiography for detection of myocardial viability was 95%. This study shows that GIK echocardiography is similar to LDDSE for detection of myocardial viability. With the support of further clinical studies GIK echocardiography can be used to detect myocardial viability in patients with chronic CAD.

Hypertension:

6899. Harrison SA, Kadakia S, Lang KA, Schenker S.Nonalcoholic steatohepatitis: what we know in the new millennium. Am J Gastroenterol 2002 Nov;97(11):2714-24

Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by diffuse fatty infiltration and inflammation. The exact prevalence of NASH is unclear, but it is becoming more evident that the disease is much more common than previously thought. Although generally a benign, indolent process, it can progress to advanced liver disease in approximately 15-20% of patients. Clinical characteristics associated with NASH include obesity, hyperlipidemia, diabetes mellitus, and hypertension, all of which have been associated with underlying insulin resistance. Typically, this disease becomes evident in the fourth or fifth decade of life with an equal sex predilection. NASH is thought to be caused, in part, by impaired insulin signaling, leading to elevated circulating insulin levels and subsequent altered lipid homeostasis. This process is likely multifactorial and includes both genetic and environmental factors. Treatment options to date are limited and are based on very small clinical trials. Current investigations are focusing on improving the underlying insulin resistance that has been associated with NASH as well as other therapies that decrease oxidative stress or improve hepatocyte survival.

6900. Minuz P, Patrignani P, Gaino S, Degan M, Menapace L, Tommasoli R, Seta F, Capone ML, Tacconelli S, Palatresi S, Bencini C, Del Vecchio C, Mansueto G, Arosio E, Santonastaso CL, Lechi A, Morganti A, Patrono C. Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease. Circulation 2002 Nov 26;106(22):2800-5

BACKGROUND: Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system. METHODS AND RESULTS: We measured the urinary excretion of 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane (TX) B2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF2alpha was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF2alpha correlated with 11-dehydro-TXB2 (r(s)=0.48; P<0.05) and renal vein renin (r(s)=0.67; P<0.005) and angiotensin II (r(s)=0.65; P=0.005) ratios. A reduction in 8-iso-PGF2alpha after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF2alpha were related to baseline lipid peroxidation (r(s)=-0.73; P<0.001), renal vein angiotensin II (r(s)=-0.70; P<0.01) and renin (r(s)=-0.63; P<0.05) ratios. CONCLUSIONS: Lipid peroxidation is markedly enhanced in hypertensive patients with RVD and is related to activation of the renin-angiotensin system. Moreover, persistent platelet activation triggered or amplified by bioactive isoprostanes may contribute to the progression of cardiovascular and renal damage in this setting.

6901. Roberts CK, Vaziri ND, Barnard RJ. Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability. Circulation 2002 Nov 12;106(20):2530-2

BACKGROUND: Diet and exercise can affect blood pressure and atherosclerotic risk. METHODS AND RESULTS: The present study was designed to examine the effects of a short-term, rigorous diet and exercise intervention on blood pressure, hyperinsulinemia, and nitric oxide (NO) availability. Men (n=11) were placed on a low-fat, high-fiber diet combined with daily exercise for 45 to 60 minutes for 3 weeks. Pre- and post fasting blood was drawn for serum lipid, insulin, 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), and glucose measurements. Anthropometric parameters, blood pressure (BP), and 24-hour urinary NO metabolite excretion (NO(X)), a marker of NO bioavailability, were measured. Systolic (P<0.01) and diastolic BP (P<0.01) and 8-iso-PGF(2alpha) decreased (P<0.05), whereas urinary NO(X) increased (P<0.05). There was a significant reduction in fasting insulin (P<0.01) and a significant correlation between the decrease in serum insulin and the increase in urinary NO(X) (r2=0.68, P<0.05). All fasting lipids decreased significantly, and the total cholesterol to high-density lipoprotein cholesterol ratio improved. Although body weight and body mass index (P<0.01) decreased, obesity was still present and there were no correlations between the change in body mass index and the change in insulin, BP, or urinary NO(X). CONCLUSIONS: This intervention resulted in dramatic improvements in BP, oxidative stress, NO availability, and the metabolic profile within 3 weeks, mitigating the risk for atherosclerosis progression and its clinical sequelae.

6902. Tsai PS. White coat hypertension: understanding the concept and examining the significance. J Clin Nurs 2002 Nov;11(6):715-22

Because the concept of white coat hypertension is evolving, a variety of definitions appear in the literature. There has also been continuing debate as to whether white coat hypertension is a benign clinical condition or is associated with increased hypertensive complications. This paper summarizes and evaluates the literature on white coat effect/hypertension, with a focus on the following aspects of the concepts: (1) alternative definitions, (2) prevalence and predictors, (3) prognostic significance, and (4) implications for clinical practice. The evidence suggests that white coat hypertension is not a harmless phenomenon. It is frequently associated with increased target-organ damage and often coexists with other cardiovascular risk factors. The extent of the presence of other risk factors may determine the risks associated with white coat hypertension. It is important for clinicians to understand the concept, learn to diagnose it properly, and develop strategies for evaluating risk levels so that patients receive the proper treatment.

July 2003

7463. Corradi M, Folesani G, Andreoli R, Manini P, Bodini A, Piacentini G, Carraro S, Zanconato S, Baraldi E. Aldehydes and glutathione in exhaled breath condensate of children with asthma exacerbation. Am J Respir Crit Care Med. 2003 Feb 1;167(3):395-9. No abstract available.

7464. Song R, Ning W, Liu F, Ameredes BT, Calhoun WJ, Otterbein LE, Choi AM. Regulation of IL-1beta -induced GM-CSF production in human airway smooth muscle cells by carbon monoxide. Am J Physiol Lung Cell Mol Physiol. 2003 Jan;284(1):L50-6. No abstract available.

7465. Tschumperlin DJ, Shively JD, Kikuchi T, Drazen JM. Mechanical stress triggers selective release of fibrotic mediators from bronchial epithelium. Am J Respir Cell Mol Biol. 2003 Feb;28(2):142-9.No abstract available.

Depression:

7466. Chaki S, Hirota S, Funakoshi T, Suzuki Y, Suetake S, Okubo T, Ishii T, Nakazato A, Okuyama S. Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxyna phthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor.J Pharmacol Exp Ther. 2003 Feb;304(2):818-26.

We investigated the effects of a novel melanocortin-4 (MC4) receptor antagonist,1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2 -methoxynaphthalen-1-yl)butyl]piperazine (MCL0129) on anxiety and depression in various rodent models. MCL0129 inhibited [(125)I][Nle(4)-D-Phe(7)]-alpha-melanocyte-stimulating hormone (alpha-MSH) binding to MC4 receptor with a K(i) value of 7.9 nM, without showing affinity for MC1 and MC3 receptors. MCL0129 at 1 microM had no apparent affinity for other receptors, transporters, and ion channels related to anxiety and depression except for a moderate affinity for the sigma(1) receptor, serotonin transporter, and alpha(1)-adrenoceptor, which means that MCL0129 is selective for the MC4 receptor. MCL0129 attenuated the alpha-MSH-increased cAMP formation in COS-1 cells expressing the MC4 receptor, whereas MCL0129 did not affect basal cAMP levels, thereby indicating that MCL0129 acts as an antagonist at the MC4 receptor. Swim stress markedly induced anxiogenic-like effects in both the light/dark exploration task in mice and the elevated plus-maze task in rats, and MCL0129 reversed the stress-induced anxiogenic-like effects. Under nonstress conditions, MCL0129 prolonged time spent in the light area in the light/dark exploration task and suppressed marble-burying behavior. MCL0129 shortened immobility time in the forced swim test and reduced the number of escape failures in inescapable shocks in the learned helplessness test, thus indicating an antidepressant potential. In contrast, MCL0129 had negligible effects on spontaneous locomotor activity, Rotarod performance, and hexobarbital-induced anesthesia. These observations indicate that MCL0129 is a potent and selective MC4 antagonist with anxiolytic- and antidepressant-like activities in various rodent models. MC4 receptor antagonists may prove effective for treating subjects with stress-related disorders such as depression and/or anxiety.

7467. Grant I, McKibbin CL, Taylor MJ, Mills P, Dimsdale J, Ziegler M, Patterson TL. In-home respite intervention reduces plasma epinephrine in stressed Alzheimer caregivers. Am J Geriatr Psychiatry. 2003 Jan-Feb;11(1):62-72.

OBJECTIVE: Some excess morbidity and mortality in Alzheimer caregivers (CGs) may be related to chronic activation of the sympatho-adrenal-medullary (SAM) system. Authors tested the efficacy of an in-home respite intervention to reduce peripheral markers of SAM activation and psychological distress in spousal caregivers of patients with Alzheimer disease. METHODS: Caregivers were classified as Vulnerable (n = 27) or Non-Vulnerable (n = 28). Vulnerable CGs were those with a severe mismatch between caregiving demand and help received in the preceding 6 months. CGs had plasma catecholamine levels sampled at rest and in response to a stressor (speech task) before and 1 month after a 2-week in-home respite intervention. Self-reported symptoms of anxiety and depression were also obtained. RESULTS: ANOVA revealed a group x treatment interaction: At the 1-month follow-up, plasma epinephrine declined significantly in the vulnerable caregivers who received respite, but rose in those who were wait-listed. No effect was found for norepinephrine, heart rate, blood pressure, or psychological symptoms. CONCLUSION: Findings suggest that an in-home respite program may reduce SAM activation independent of psychological symptoms. To the extent that sympathetic activation mediates pathophysiological events, these results suggest an approach that may reduce morbidity and mortality in certain caregivers.

7468. Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, Yeo KP, Reddy S, Lim M, Ayan-Oshodi M, Wise SD. Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers.Clin Pharmacol Ther. 2003 Mar;73(3):170-7.

BACKGROUND AND OBJECTIVES: Duloxetine, a potent dual reuptake inhibitor of serotonin and norepinephrine currently undergoing clinical investigation for treatment of depression and stress urinary incontinence, has the potential to act as both a substrate and an inhibitor of cytochrome P4502D6 (CYP2D6). Our objectives were to determine the effect of duloxetine on the pharmacokinetics of desipramine, a tricyclic antidepressant metabolized by CYP2D6 (study 1), and the effect of paroxetine, a potent CYP2D6 inhibitor, on duloxetine pharmacokinetics (study 2). METHODS: Subjects were healthy men and women between 21 and 63 years old. All subjects were genotypically CYP2D6 extensive metabolizers. In study 1, 50 mg of desipramine was administered as a single dose alone and in the presence of steady-state duloxetine 60 mg twice daily. In study 2, steady-state pharmacokinetics of duloxetine 40 mg once daily were determined in the presence and absence of steady-state paroxetine 20 mg once daily. RESULTS: Duloxetine increased the maximum plasma concentration of desipramine 1.7-fold and the area under the concentration-time curve 2.9-fold. Paroxetine increased the maximum plasma concentration of duloxetine and the area under the concentration-time curve at steady state 1.6-fold. Reports of adverse events were similar whether duloxetine was administered alone or in combination with desipramine or paroxetine. CONCLUSION: Duloxetine 60 mg twice daily is a moderately potent CYP2D6 inhibitor, intermediate between paroxetine and sertraline. The potent CYP2D6 inhibitor paroxetine has a moderate effect on duloxetine concentrations. The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine.

Heart Disease

7469. Bairey Merz CN, Johnson BD, Sharaf BL, Bittner V, Berga SL, Braunstein GD, Hodgson TK, Matthews KA, Pepine CJ, Reis SE, Reichek N, Rogers WJ, Pohost GM, Kelsey SF, Sopko G. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol. 2003 Feb 5;41(3):413-9.

OBJECTIVES: We sought to evaluate hypoestrogenemia of hypothalamic origin and its association with angiographic coronary artery disease (CAD) in premenopausal women. BACKGROUND: Coronary artery disease in premenopausal women appears to have a particularly poor prognosis. Primate animal data suggest that premenopausal CAD is strongly determined by psychosocial stress-induced central disruption of ovulatory cycling and resulting hypoestrogenemia. METHODS: We assessed reproductive hormone blood levels and angiographic CAD using core laboratories in 95 premenopausal women with coronary risk factors who were enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation and were undergoing coronary angiography for evaluation for suspected ischemia. RESULTS: Premenopausal women with angiographic CAD (n = 13) had significantly lower estradiol, bioavailable estradiol, and follicle-stimulating hormone (FSH) (all p < 0.05) than women without angiographic CAD (n = 82), even after controlling for age. Hypoestrogenemia of hypothalamic origin, defined as estradiol <184 pmol/l (50 pg/ml), FSH <10 IU/l, and luteinizing hormone <10 IU/l, was significantly more prevalent among the women with CAD than those without CAD (9/13 [69%] vs. 24/82 [29%], respectively, p = 0.01). Hypoestrogenemia of hypothalamic origin was the most powerful predictor of angiographic CAD in a multivariate model (odds ratio [OR] 7.4 [confidence interval (CI) 1.7 to 33.3], p = 0.008). Anxiolytic/sedative/hypnotic and antidepressant medication use were independent predictors of hypoestrogenemia of hypothalamic origin in a multivariate model (OR 4.6 [CI 1.3 to 15.7], p = 0.02, OR 0.10 [CI 0.01 to 0.92], p = 0.04, respectively). CONCLUSIONS: Among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, disruption of ovulatory cycling characterized by hypoestrogenemia of hypothalamic origin appears to be associated with angiographic CAD.

7470. Beattie MS, Shlipak MG, Liu H, Browner WS, Schiller NB, Whooley MA. C-reactive protein and ischemia in users and nonusers of beta-blockers and statins: data from the Heart and Soul Study. Circulation. 2003 Jan 21;107(2):245-50.

BACKGROUND: Elevated levels of C-reactive protein (CRP) are associated with an increased risk of coronary events, but whether inflammation is associated with inducible ischemia in patients with stable coronary disease is unknown. METHODS AND RESULTS: We recruited patients with known coronary disease from 2 VA Medical Centers and 1 University-based medical center for the Heart and Soul Study. We measured CRP levels in 118 participants who had exercise-induced ischemia and in 111 who did not have inducible ischemia, as determined by stress echocardiography. We used logistic regression to examine the risk of exercise-induced ischemia associated with elevated CRP. We found that 75% (39/52) of participants in the highest CRP category (>0.38 mg/dL) had inducible ischemia, compared with 45% (79/177) in the lower 4 categories combined (adjusted odds ratio 4.2; 95% confidence interval 1.6 to 11; P=0.004). However, this association differed in users and nonusers of beta-blockers and statins. Among 89 participants who did not use beta-blockers, 93% in the highest CRP category had exercise-induced ischemia, compared with 42% in the lower 4 categories (P=0.03). Among 67 participants who did not use statins, 94% in the highest CRP category had exercise-induced ischemia, compared with 44% in the lower 4 categories (P=0.009). We did not observe a significant association between CRP and ischemia among participants who were treated with either of these medications. CONCLUSION: Elevated CRP levels are associated with inducible ischemia in patients with stable coronary disease, particularly among those not treated with beta-blockers or statins.

7471. Cipollone F, Ganci A, Greco A, Panara MR, Pasquale M, Di Gregorio D, Porreca E, Mezzetti A, Cuccurullo F, Patrignani P. Modulation of aspirin-insensitive eicosanoid biosynthesis by 6-methylprednisolone in unstable angina. Circulation. 2003 Jan 7;107(1):55-61.

BACKGROUND: The evidence that inflammation plays a pivotal role in the pathophysiology of acute coronary syndromes prompted us to investigate the effects of glucocorticoid treatment on leukotriene (LT) C4 and thromboxane (TX) A2 biosynthesis in unstable angina. METHODS AND RESULTS: Urinary LTE4 and 11-dehydro-TXB2 were significantly higher in 12 patients with unstable angina than in 12 patients with stable angina and 12 patients with nonischemic chest pain. Furthermore, we randomized the unstable angina patients to receive intravenous 6-methylprednisolone (6-MP; 1 mg/kg BID for 2 days) or matching placebo and collected 12 consecutive 6-hour urine samples before and during the infusions. LTE4 excretion showed a time-dependent decrease in the 6-MP group but did not decrease during placebo. Furthermore, during myocardial ischemia, LTE4 was significantly higher before 6-MP infusion than during steroid therapy. In contrast, 11-dehydro-TXB2 did not differ significantly during 6-MP versus placebo. Myocardial ischemia elicited by stress test in the stable angina patients was not accompanied by any change in LTE4 and 11-dehydro-TXB2, thus ruling out a role of ischemia per se in the induction of increased eicosanoid production. CONCLUSIONS: Increased production of vasoactive LT and TX may occur in unstable angina despite conventional antithrombotic and antianginal treatment. Glucocorticoids can suppress LTC4 biosynthesis in the short term and may provide an interesting tool to explore the pathophysiological significance of inflammatory cell activation in this setting.

7472. Foo K, Sekhri N, Deaner A, Knight C, Suliman A, Ranjadayalan K, Timmis AD. Effect of diabetes on serum potassium concentrations in acute coronary syndromes. Heart. 2003 Jan;89(1):31-5.

OBJECTIVES: To compare serum potassium concentrations in diabetic and non-diabetic patients in the early phase of acute coronary syndromes. BACKGROUND: Acute phase hypokalaemia occurs in response to adrenergic activation, which stimulates membrane bound sodium-potassium-ATPase and drives potassium into the cells. It is not known whether the hypokalaemia is attenuated in patients with diabetes because of the high prevalence of sympathetic nerve dysfunction. METHODS: Prospective cohort study of 2428 patients presenting with acute coronary syndromes. Patients were stratified by duration of chest pain, diabetic status, and pretreatment with beta blockers. RESULTS: The mean (SD) serum potassium concentration was significantly higher in diabetic than in non-diabetic patients (4.3 (0.5) v 4.1 (0.5) mmol/l, p < 0.0001). Multivariate analysis identified diabetes as an independent predictor of a serum potassium concentration in the upper half of the distribution (odds ratio 1.66, 95% confidence interval 1.38 to 2.00). In patients presenting within 6 hours of symptom onset, there was a progressive increase in plasma potassium concentrations from 4.08 (0.46) mmol/l in patients presenting within 2 hours, to 4.20 (0.47) mmol/l in patients presenting between 2-4 hours, to 4.24 (0.52) mmol/l in patients presenting between 4-6 hours (p = 0.0007). This pattern of increasing serum potassium concentration with duration of chest pain was attenuated in patients with diabetes, particularly those with unstable angina. Similar attenuation occurred in patients pretreated with beta blockers. CONCLUSION: In acute coronary syndromes, patients with diabetes have significantly higher serum potassium concentrations and do not exhibit the early dip seen in non-diabetics. This may reflect sympathetic nerve dysfunction that commonly complicates diabetes.

7473. Gresele P, Guglielmini G, De Angelis M, Ciferri S, Ciofetta M, Falcinelli E, Lalli C, Ciabattoni G, Davi G, Bolli GB. Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus. J Am Coll Cardiol. 2003 Mar 19;41(6):1013-20.

OBJECTIVES: The aim of our study was to assess whether acute, short-term hyperglycemia affects platelet reactivity in patients with Type II diabetes mellitus (T2DM). BACKGROUND: Hyperglycemic spikes are thought to precipitate ischemic events in T2DM. Previous studies have shown in vivo platelet activation in diabetes; however, no studies have assessed whether acute in vivo hyperglycemia induces further activation of platelets. METHODS: In a cross-over, randomized, double-blind study, 12 patients with T2DM underwent 4 h of either acute hyperglycemia (13.9 mmol/l, 250 mg/dl) or euglycemia (5.5 mmol/l, 100 mg/dl). Shear stress-induced platelet activation, P-selectin and lysosomal integral membrane protein (LIMP) expression on platelets in the bleeding-time blood, urinary 11-dehydro-thromboxane B(2) (TxB(2)) excretion, von Willebrand factor:antigen (vWF:Ag), and von Willebrand factor:activity (vWF:activity) were measured before and after hyperglycemia or euglycemia. RESULTS: Shear stress-induced platelet activation, P-selectin and LIMP expression on platelets in the bleeding-time blood, and urinary 11-dehydro-TxB(2) excretion increased significantly after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping. Plasma vWF:Ag and vWF:activity increased strikingly in parallel fashion after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping. CONCLUSIONS: Our data demonstrate that acute, short-term hyperglycemia induces an increased activation of platelets exposed to high shear stress conditions in vitro (filtration method) or in vivo (bleeding time). In vivo platelet activation is reflected by an increased urinary excretion of 11-dehydro-TxB(2). The increased levels of vWF in the circulation correlate with the increase in platelet activation markers and may indicate some degree of causation. Acute, short-term hyperglycemia in T2DM may precipitate vascular occlusions by facilitating platelet activation.

7474. Koertge JC, Ahnve S, Schenck-Gustafsson K, Orth-Gomer K, Wamala SP. Vital exhaustion in relation to lifestyle and lipid profile in healthy women. Int J Behav Med. 2003;10(1):44-55.

"Vital exhaustion," characterized by fatigue, irritability, and demoralization, precedes new and recurrent coronary events. Biological mechanisms explaining this association are not fully understood. The objective was to investigate the relationship between vital exhaustion, lifestyle, and lipid profile. Vital exhaustion, smoking, body mass index (BMI), alcohol consumption, exercise capacity, and serum lipids were determined in 300 healthy women, aged 56.4 +/- 7.1 years. No statistically significant associations were found between vital exhaustion and lifestyle variables. Divided into quartiles, vital exhaustion was inversely related to high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 in a linear fashion after adjustment for age, BMI, exercise capacity, and alcohol consumption. A multivariate-adjusted vital exhaustion-score in the top quartile, as compared to one in the lowest, was associated with 12% lower HDL-C and 8% lower apolipoprotein A1 (p < .05). In conclusion, alterations in lipid metabolism may be a possible mediating mechanism between vital exhaustion and coronary heart disease. The impact of lifestyle variables was weak.

7475. Mehlhorn U, Krahwinkel A, Geissler HJ, LaRosee K, Fischer UM, Klass O, Suedkamp M, Hekmat K, Tossios P, Bloch W. Nitrotyrosine and 8-isoprostane formation indicate free radical-mediated injury in hearts of patients subjected to cardioplegia. J Thorac Cardiovasc Surg. 2003 Jan;125(1):178-83.

OBJECTIVE: Myocardial ischemia and reperfusion induced by cardioplegic arrest subjects the heart to free radical-mediated stress. The purpose of our study was to investigate the effect of cardioplegia-induced ischemia and reperfusion on myocardial formation and distribution of (1) nitrotyrosine as an indicator for peroxynitrite-mediated tissue injury resulting from increased nitric oxide release and (2) 8-isoprostane as an indicator for oxygen-derived free radical-mediated lipid peroxidation. METHODS: In 10 patients undergoing coronary artery operations (64 +/- 6 [mean +/- SD] years, 3 women and 7 men) subjected to cardiopulmonary bypass and intermittent cold blood cardioplegia, we collected transmural left ventricular biopsy specimens before and at the end of cardiopulmonary bypass. Specimens were cut at 10 micro m and subjected to immunocytochemical staining against the nitric oxide-producing enzyme constitutive nitric oxide synthase, cyclic guanosine monophosphate (intracellular second messenger of nitric oxide), nitrotyrosine, and 8-isoprostane by using polyclonal antibodies. For global left ventricular function determination, we measured the fractional area of contraction using transesophageal echocardiography. RESULTS: Nitric oxide synthase activity in cardiac myocytes increased from 34 +/- 10 gray units before cardiopulmonary bypass to 47 +/- 12 gray units at the end of bypass (P =.015), and all hearts showed increased cyclic guanosine monophosphate content in both myocytes and endothelial cells at the end of bypass. The number of nitrotyrosine-positive capillaries increased from 36 +/- 29/mm(2) before bypass to 82 +/- 47/mm(2) at the end of bypass (P =.012), and 8-isoprostane-positive capillaries increased from 92 +/- 72/mm(2) before bypass to 209 +/- 108/mm(2) at the end of bypass (P =.005). The fractional area of contraction was 53% +/- 12% before bypass and 56% +/- 12% after bypass (P =.47) but was slightly decreased to 45% +/- 14% at 4 hours after bypass (P =.121). CONCLUSIONS: Our data show that cardioplegia-induced myocardial ischemia and reperfusion is associated with nitrotyrosine and 8-isoprostane formation mainly in the coronary endothelium, indicating injury mediated by both peroxynitrite and oxygen-derived free radicals. Because nitric oxide synthase activation was accompanied with increased cyclic guanosine monophosphate, these data suggest that direct effects of nitric oxide on cardiac myocytes, as well as nitric oxide-mediated coronary endothelial injury, might contribute to injury associated with cardioplegia and cardiopulmonary bypass.

7476. Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT. Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation. 2003 Feb 11;107(5):721-6.

BACKGROUND: Using genomic technology, we previously identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes. The soluble receptor form of ST2 is secreted and detectable in human serum. This study tested the hypothesis that soluble ST2 levels in the serum of patients with severe chronic heart failure are increased in patients with neurohormonal activation. METHODS AND RESULTS: Serum samples, clinical variables, and neurohormone levels from the PRAISE-2 heart failure trial (NYHA functional class III-IV; end point, mortality or transplantation) were analyzed. ST2 serum measurements were performed with ELISA on samples from 161 patients obtained at trial enrollment and from 139 of the same patients obtained 2 weeks after trial enrollment. Baseline ST2 levels were correlated with baseline B-type natriuretic peptide (BNP) levels (r=0.36, P<0.0001), baseline proatrial natriuretic peptide (ProANP) levels (r=0.36, P<0.0001), and baseline norepinephrine levels (r=0.39, P<0.0001). The change in ST2 was significant as a univariate predictor of subsequent mortality or transplantation (P=0.048), as was baseline BNP (P<0.0001) and baseline ProANP (P<0.0001). In multivariate models including BNP and ProANP, the change in ST2 remained significant as a predictor of mortality or transplantation independent of BNP and ProANP. CONCLUSIONS: Serum soluble ST2 is a novel biomarker for neurohormonal activation in patients with heart failure. In patients with severe chronic NYHA class III to IV heart failure, the change in ST2 levels is an independent predictor of subsequent mortality or transplantation.

Hypertension:

7477. Aikio O, Vuopala K, Pokela ML, Andersson S, Hallman M. Nitrotyrosine and NO synthases in infants with respiratory failure: influence of inhaled NO. Pediatr Pulmonol. 2003 Jan;35(1):8-16.

Inhaled nitric oxide (NO) is a selective vasodilator in pulmonary hypertension. However, the safety of inhaled NO (iNO) has not been established. Using an immunohistochemical technique, we studied the expression of NO synthase (NOS) isoforms NOS1, NOS2, NOS3, and nitrotyrosine, the marker of toxic NO-superoxide pathway, in lung specimens from autopsies. Twelve infants dying with respiratory failure had iNO up to 60 parts per million for 0.1-15 days. Twelve control infants were matched in pairs on the basis of the diagnosis, number of gestational days at birth, age at death, and whether extracorporeal perfusion was required. In addition, 5 infants who died of SIDS or nonpulmonary trauma (healthy lungs) were compared to 8 age-matched cases with respiratory failure. Immunostaining was graded by the intensity of the color deposit and the frequency in specific cells stained. Inhaled NO tended to increase NOS2 expression in bronchiolar epithelium and adjacent tissue. There were no other differences in the distribution of nitrotyrosine or NOS isoforms between iNO-treated infants and the control group with respiratory failure. All NOS isoforms were evident in the lungs studied. In severe respiratory failure, nitrotyrosine was mostly detectable in the bronchiolar epithelium and alveolar exudates, whereas in healthy lungs those sites did not contain nitrotyrosine. The alveolar tissue of infants with progressive respiratory may be affected by the NO-superoxide pathway. However, inhalation of NO was not associated with a detectable increase in oxidant stress. Copyright 2003 Wiley-Liss, Inc.

7478. Cracowski JL, Baguet JP, Ormezzano O, Bessard J, Stanke-Labesque F, Bessard G, Mallion JM. Lipid peroxidation is not increased in patients with untreated mild-to-moderate hypertension. Hypertension. 2003 Feb;41(2):286-8.

In contrast with the huge amount of experimental data available, only few and somewhat unconvincing clinical studies support the hypothesis that oxidative stress is involved in the early stages of essential hypertension in humans. Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of 15-F(2t)-IsoP in the early stages of essential hypertension, using gas chromatography/mass spectrometry, by comparing 30 patients with never-treated mild-to-moderate hypertension with 30 gender- and age-paired healthy controls. Urinary 15-F(2t)-IsoP levels were not significantly different in hypertensive patients (69+/-36 pmol/mmol creatinine) compared with controls (75+/-34 pmol/mmol creatinine, 95% confidence intervals on differences: -23 to 13). No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and age, low-density lipoprotein cholesterol, glucose, clinical pulse pressure, carotid intima-media thickness, left ventricular mass index, or aortic pulse wave velocity. In conclusion, this study shows that lipid peroxidation is not increased in never-treated mild-to-moderate hypertension. This suggests that oxidative stress is not implicated in the pathogenesis of human essential hypertension, at least in the early stages.

7479. Perna AF, Ingrosso D, Lombardi C, Cesare CM, Acantora F, Satta E, De Santo NG. Homocysteine in uremia. Am J Kidney Dis. 2003 Mar;41(3 Suppl 2):S123-6.

Hyperhomocysteinemia is an independent cardiovascular risk factor that possibly accounts for about one of 5 cardiovascular deaths. It is conceivable that the importance of hyperhomocysteinemia will increase when other risk factors, such as hypertension or hypercholesterolemia, will become less prevalent in the general population. In chronic renal failure (CRF), high plasma homocysteine levels are a common finding and in uremia almost the rule. However, a small subset of patients remains normohomocysteinemic. The cause of hyperhomocysteinemia in CRF, whether it lies in an impaired renal or extrarenal metabolism or through uremic retention toxins, is still under intensive scrutiny. As for the consequences of high homocysteine levels in the general population and in patients with CRF, these are many-fold and linked to the mechanism of homocysteine toxic action. In fact, homocysteine can be harmful to cells because (1) it evokes oxidative stress (through the production of reactive oxygen species), (2) binds to nitric oxide, (3) produces homocysteinylated proteins, or (4) leads to the accumulation of its precursor, S-adenosylhomocysteine, a potent inhibitor of biological transmethylations. Macromolecule hypomethylation is a common feature in CRF and uremia with possible functional consequences. Nutritional or pharmacologic interventions have been proposed in the treatment of hyperhomocysteinemia, while the results of large clinical trials designed to assess if lowering homocysteine levels is effective in reducing cardiovascular risk, are pending.

7480. Piuhola J, Szokodi I, Kinnunen P, Ilves M, deChatel R, Vuolteenaho O, Ruskoaho H. Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts. Hypertension. 2003 Jan;41(1):93-8.

Endothelin-1 is involved in mechanical load-induced cardiac growth processes; it also has effects on contractility. The interaction of endothelin-1 and the Frank-Starling response is unknown. The present study aimed to characterize the role of endothelin-1 in the regulation of the Frank-Starling response, one of the major mechanisms regulating cardiac contractile force, in both normal and hypertrophied hearts. Nontransgenic rat hearts and hypertrophic hearts of hypertensive double transgenic rats harboring human angiotensinogen and renin genes were studied in a Langendorff isolated heart setup with a liquid-filled balloon inside the left ventricle used to measure contractile parameters. The rats were studied at compensated phase, before showing any signs of heart failure. Compensated hypertrophy in double transgenic rat hearts resulted in improved contractility at a given level of preload when compared with nontransgenic rat hearts. Hearts of both rat lines showed preserved Frank-Starling responses, that is, increased contractile function in response to increased end-diastolic pressure. The mixed endothelin A/B receptor antagonist bosentan attenuated the Frank-Starling response by 53% (P<0.01) in the double transgenic hearts but not in nontransgenic hearts. The diastolic parameters remained unaffected. The left ventricles of the double transgenic rat hearts showed an 82% higher level of endothelin type A receptor mRNA and a 25% higher level of immunoreactive endothelin-1 compared with nontransgenic rat hearts. The type 1 angiotensin II receptor antagonist CV-11974 had no significant effect on contractile function in response to load in either strain. These results show that endogenous endothelin-1 contributes to the Frank-Starling response in hypertrophied rat hearts by affecting systolic performance.

7481. Pollard TM, Schwartz JE. Are changes in blood pressure and total cholesterol related to changes in mood? An 18-month study of men and women. Health Psychol. 2003 Jan;22(1):47-53.

The authors investigated the within-person association of reported mood with blood pressure and total cholesterol (TC) levels, each assessed 4 times over an 18-month period in 128 men and 154 women. Change over time in tense arousal was significantly positively associated with changes over time in systolic blood pressure (SBP) and diastolic blood pressure (DBP) but not TC. A change in hedonic tone was significantly associated with SBP (an increase in negative affect was associated with an increase in SBP) but not with DBP or TC. There were no sex differences in associations of mood with SBP or TC. However, increases in tense arousal and negative affect were significantly associated with an increase in DBP for women but not men.

7482. Ranade J, Bhaduri J, Rane S, Oroskar S,Gaikwad S. Effect and tolerability of anxicalm in patients of anxiety associated with hypertension. Cardial Today 2002, 6(4), 169-73. (22903)Vol 38, No. 22, 16 Nov 2002.

7483. Rowley K, O'Dea K, Best JD. Association of albuminuria and the metabolic syndrome. Curr Diab Rep. 2003 Feb;3(1):80-6.

Microalbuminuria clusters with the metabolic syndrome, and both conditions predict cardiovascular disease mortality. The reported relationships of microalbuminuria with the individual components of the metabolic syndrome (i.e., hyperglycemia, insulin resistance, hypertension, dyslipidemia, abdominal obesity) are variable. Each of these components, as well as intrauterine effects and diet and other lifestyle factors, may contribute to elevated risk of microalbuminuria in certain population groups. Recent evidence indicates a role for oxidation and inflammation in cardiovascular disease, and endothelial dysfunction (exacerbated by factors such as dyslipidemia) may be the mediator of this relationship. Because endothelial dysfunction can also be manifested as microalbuminuria, this provides a potential explanation of the observed association of the metabolic syndrome, chronic inflammation, and microalbuminuria.

October 2003

Asthma:

8132. Baraldi E, Carraro S, Alinovi R, Pesci A, Ghiro L, Bodini A, Piacentini G, Zacchello F, Zanconato S. Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations. Thorax. 2003 Jun;58(6):505-9.

BACKGROUND: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. METHODS: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. RESULTS: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Biochemical Indicators:

8133. Benderitter M, Vincent-Genod L, Pouget JP, Voisin P. The cell membrane as a biosensor of oxidative stress induced by radiation exposure: a multiparameter investigation. Radiat Res. 2003 Apr;159(4):471-83.

The role of biological membranes as a target in biological radiation damage remains unclear. The present study investigates how the biochemical and biophysical properties of a simple biological model, i.e. human erythrocyte membranes, are altered after exposure to relatively low doses of (60)Co gamma rays. Lipid peroxidation increased in the hours after radiation exposure, based on measurements of MDA and on the lipid peroxidation index after parinaric acid incorporation. Protein carbonyl content also increased rapidly after radiation exposure. An imbalance between the radiation-mediated oxidative damages and the antioxidant capacity of the erythrocytes was observed in the hours after radiation exposure. Antioxidant enzyme activities, mainly catalase and glutathione peroxidase, were found to decrease after irradiation. The development of a radiation-induced oxidative stress probably explains the reorganization of the fatty acid pattern 72 h after radiation exposure. The phosphatidylethanolamine (PE) fatty acids of the (n-3) and (n-6) series decreased, while the PE saturated fatty acid content increased. All these modifications may be involved in the variation of the biophysical properties of the membranes that we noted after radiation exposure. Specifically, we observed that the lipid compartment of the membrane became more fluid while the lipid-protein membrane interface became more rigid. Taken together, these findings reinforce our understanding that the cell membrane is a significant biological target of radiation. Thus the role of the biological membrane in the expression and course of cell damage after radiation exposure must be considered.

Depression:

8134. Cosin-Sales J, Pizzi C, Brown S, Kaski JC. C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms. J Am Coll Cardiol. 2003 May 7;41(9):1468-74.

OBJECTIVES: We sought to investigate the relationship among C-reactive protein (hs-CRP), clinical characteristics, exercise stress test responses, and ST-segment changes during daily life in patients with typical chest pain and normal coronary angiograms (CPNCA). BACKGROUND: Patients with CPNCA have coronary microvascular endothelial dysfunction and myocardial ischemia. Elevated hs-CRP levels have been related to atherogenesis and endothelial dysfunction. The relationship between hs-CRP and disease activity has not been previously investigated in CPNCA patients. METHODS: We studied 137 consecutive CPNCA patients (mean age, 57 +/- 9; 33 men). All completed standardized angina questionnaires, underwent exercise stress testing, 24-h ambulatory electrocardiogram (ECG) monitoring (Holter), and hs-CRP measurements at study entry. RESULTS: C-reactive protein levels (mg/l) were higher in patients with frequent (2.9 +/- 3.3) and prolonged (3.9 +/- 4.1) chest pain episodes, and in those with ST-segment depression on exercise testing (2.6 +/- 2.8) and Holter monitoring (3.4 +/- 3.1) compared with patients with occasional (1.3 +/- 1.2; p = 0.002) or shorter chest pain (1.5 +/- 1.3; p < 0.001) episodes, negative exercise stress testing (1.1 +/- 1.1; p < 0.001), and no ST-segment shifts on Holter monitoring (0.9 +/- 0.7; p < 0.001). Moreover, we found a correlation between hs-CRP concentration and number of ischemic episodes during Holter monitoring (r = 0.65; p < 0.001) and with the magnitude of ST-segment depression on exercise testing (r = -0.43; p < 0.001). The hs-CRP was the only independent variable (multivariate logistic regression) capable of predicting positive findings on Holter monitoring (odds ratio [OR], 3.8; confidence interval [CI], 2.3 to 6.2) and exercise testing (OR, 1.7; CI, 1.2 to 2.2). CONCLUSIONS: The hs-CRP correlates with symptoms and ECG markers of myocardial ischemia in CPNCA patients. Whether hs-CRP is related to the pathogenesis of angina in these patients deserves further investigation.

8135. Dickerson LM, Mazyck PJ, Hunter MH. Premenstrual syndrome. Am Fam Physician. 2003 Apr 15;67(8):1743-52. Review.

Premenstrual syndrome, a common cyclic disorder of young and middle-aged women, is characterized by emotional and physical symptoms that consistently occur during the luteal phase of the menstrual cycle. Women with more severe affective symptoms are classified as having premenstrual dysphoric disorder. Although the etiology of these disorders remains uncertain, research suggests that altered regulation of neurohormones and neurotransmitters is involved. Premenstrual syndrome and premenstrual dysphoric disorder are diagnoses of exclusion; therefore, alternative explanations for symptoms must be considered before either diagnosis is made. The disorders can manifest with a wide variety of symptoms, including depression, mood lability, abdominal pain, breast tenderness, headache, and fatigue. Women with mild symptoms should be instructed about lifestyle changes, including healthy diet, sodium and caffeine restriction, exercise, and stress reduction. Supportive strategies, such as use of a symptom diary, may be helpful in diagnosing and managing the disorders. In women with moderate symptoms, treatment includes both medication and lifestyle modifications. Dietary supplements, such as calcium and evening primrose oil, may offer modest benefit. Selective serotonin reuptake inhibitors such as fluoxetine and sertraline are the most effective pharmacologic agents. Prostaglandin inhibitors and diuretics may provide some relief of symptoms. Only weak evidence supports the effectiveness of gonadotropin-releasing hormone agonists, androgenic agents, estrogen, progesterone, or other psychotropics, and side effects limit their use.

8136. Drevets WC. Neuroimaging abnormalities in the amygdala in mood disorders. Ann N Y Acad Sci. 2003 Apr;985:420-44. Review.

Neuroimaging technology has been applied to investigate the pathophysiology of mood disorders in studies aimed at characterizing the anatomical correlates of depressive symptoms, the neurophysiological effects of antidepressant treatments, and the trait-like abnormalities that persist despite symptom remission. These studies have identified cerebral blood flow and metabolic differences between depressives and controls in the amygdala and anatomically related areas of the prefrontal cortex, striatum, and thalamus. Taken together with converging evidence from neuroendocrine, lesion analysis, and postmortem studies of clinically depressed subjects, these data suggest that emotional/stress-response systems that include the amygdala are pathologically activated in major depression and that this activity is associated with dysfunction of the prefrontal cortex and monoamine neurotransmitter systems that normally modulate such responses.

8137. Fukao A, Takamatsu J, Murakami Y, Sakane S, Miyauchi A, Kuma K, Hayashi S, Hanafusa T. The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients with Graves' disease. Clin Endocrinol (Oxf). 2003 May;58(5):550-5.

OBJECTIVE: The relationship between emotional stress and the onset of hyperthyroidism has been well investigated, but the relationship between psychological factors and prognosis of antithyroid drug-treated hyperthyroidism is not well known. This study has examined not only emotional stresses but also patients' personality traits using specific tests. DESIGN: A prospective cohort study. SUBJECTS: Sixty-nine patients with hyperthyroid Graves' disease in the euthyroid state after 2-5 years of antithyroid drug therapy and 32 healthy subjects as the control group. MEASUREMENTS: Patients responded to three types of questionnaires, including the Minnesota Multiphasic Personality Inventory for personality traits, the Natsume's Stress Inventory for major life events, and the Hayashi's Daily Life Stress Inventory for daily life stresses. RESULTS: In the Graves' disease patients, stress scores of life events correlated significantly with serum TSH receptor antibody activity (r = 0.424, P < 0.001) and thyroid volume (r = 0.480, P < 0.001). When the patients were divided according to prognosis (41 with relapse and 28 with remission), four personality traits including hypochondriasis, depression, paranoia and psychasthenia (mental fatigue) were significantly (P = 0.0146, 0.0052, 0.0125, and 0.0186, respectively) more common in the relapsed Graves' disease group than those of the remitted group. Six personality traits of conversion hysteria, psychopathic deviation, masculinity and feminity, schizophrenia, hypomania, and social introversion were not significantly different between the two groups. The scores of daily hassles (problems of daily life) were also significantly (P = 0.0124) greater in the relapsed Graves' disease group than in the remitted group. The scale scores of depression and psychasthenia showed a positive correlation with scores of daily hassles (r = 0.535, P < 0.0001; r = 0.580, P < 0.0001, respectively), while an inverse correlation with scores of daily uplifts (r = -0.373, P = 0.0332; r = -0.322, P = -0.0120, respectively). CONCLUSIONS: The results suggest that major life events, personality traits of hypochondriasis and depression, paranoia, mental fatigue, and daily problems aggravate the prognosis of antithyroid drug-treated hyperthyroidism. Escape from life events is virtually impossible; thus coping strategies suggested by the physician may be useful in improving prognosis in Graves' disease.

8138. Haag M. Essential fatty acids and the brain. Can J Psychiatry. 2003 Apr;48(3):195-203. Review.

OBJECTIVE: To review the role of essential fatty acids in brain membrane function and in the genesis of psychiatric disease. METHOD: Medline databases were searched for published articles with links among the following key words: essential fatty acids, omega-3 fatty acids, docosahexanoic acid, eicosapentanoic acid, arachidonic acid, neurotransmission, phospholipase A2, depression, schizophrenia, mental performance, attention-deficit hyperactivity disorder, and Alzheimer's disease. Biochemistry textbooks were consulted on the role of fatty acids in membrane function, neurotransmission, and eicosanoid formation. The 3-dimensional structures of fatty acids were obtained from the Web site of the Biochemistry Department, University of Arizona (2001). RESULTS: The fatty acid composition of neuronal cell membrane phospholipids reflects their intake in the diet. The degree of a fatty acid's desaturation determines its 3-dimensional structure and, thus, membrane fluidity and function. The ratio between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), in particular, influences various aspects of serotoninergic and catecholaminergic neurotransmission, as shown by studies in animal models. Phospholipase A2 (PLA2) hydrolyzes fatty acids from membrane phospholipids: liberated omega-6 PUFAs are metabolized to prostaglandins with a higher inflammatory potential, compared with those generated from the omega-3 family. Thus the activity of PLA2 coupled with membrane fatty acid composition may play a central role in the development of neuronal dysfunction. Intervention trials in human subjects show that omega-3 fatty acids have possible positive effects in the treatment of various psychiatric disorders, but more data are needed to make conclusive directives in this regard. CONCLUSION: The ratio of membrane omega-3 to omega-6 PUFAs can be modulated by dietary intake. This ratio influences neurotransmission and prostaglandin formation, processes that are vital in the maintenance of normal brain function.

8139. Nieuwenhuijsen K, de Boer AG, Verbeek JH, Blonk RW, van Dijk FJ. The Depression Anxiety Stress Scales (DASS): detecting anxiety disorder and depression in employees absent from work because of mental health problems. Occup Environ Med. 2003 Jun;60 Suppl 1:i77-82.

AIMS: To (1) evaluate the psychometric properties and (2) examine the ability to detect cases with anxiety disorder and depression in a population of employees absent from work because of mental health problems. METHODS: Internal consistency, construct validity, and criterion validity of the Depression Anxiety Stress Scales (DASS) were assessed. Furthermore, the ability to identify anxiety disorders or depression was evaluated by calculating posterior probabilities of these disorders following positive and negative test results for different cut off scores of the DASS-Depression and DASS-Anxiety subscales. RESULTS: Internal consistency of the DASS subscales was high, with Cronbach's alphas of 0.94, 0.88, and 0.93 for depression, anxiety, and stress respectively. Factor analysis revealed a three factor solution, which corresponded well with the three subscales of the DASS. Construct validity was further supported by moderately high correlations of the DASS with indices of convergent validity (0.65 and 0.75), and lower correlations of the DASS with indices of divergent validity (range -0.22 to 0.07). Support for criterion validity was provided by a statistically significant difference in DASS scores between two diagnostic groups. A cut off score of 5 for anxiety and 12 for depression is recommended. The DASS showed probabilities of anxiety and depression after a negative test result of 0.05 and 0.06 respectively. Probabilities of 0.29 for anxiety disorder and 0.33 for depression after a positive test result reflect relatively low specificity of the DASS. CONCLUSION: The psychometric properties of the DASS are suitable for use in an occupational health care setting. The DASS can be helpful in ruling out anxiety disorder and depression in employees with mental health problems.

8140. Raina AK, Hochman A, Ickes H, Zhu X, Ogawa O, Cash AD, Shimohama S, Perry G, Smith MA. Apoptotic promoters and inhibitors in Alzheimer's disease: Who wins out? Prog Neuropsychopharmacol Biol Psychiatry. 2003 Apr;27(2):251-4. Review.

A spectrum of apoptotic mediators are seen in neurons that are vulnerable in Alzheimer's disease (AD), leading many investigators to suggest that neuronal death in AD is mediated by an apoptotic process. Indeed, the environment of the AD brain is awash with proapoptotic mediators including amyloid-beta, oxidative stress, hydroxynonenal oxidants and metabolic alterations with concomitant energy failures. However, the phenotype that defines the terminal events that are pathogonomic of apoptosis, such as chromatin condensation, apoptotic bodies and membrane blebbing, are not seen in AD. Therefore, we speculated that, although AD presents with a proapoptotic environment, apoptosis does not proceed to completion. In this regard, we found that while the initiator phases of apoptosis were engaged, this does not lead to the activation of the terminal commitment phase necessary for apoptotic cell death. In other words, in AD, there is a lack of effective apoptotic signal propagation to distal effectors. This is a novel phenomenon (which we term abortosis) that represents an inhibition of apoptosis at the postinitiator stage in neurons that survive in AD.

8141. Smith MS, Martin-Herz SP, Womack WM, Marsigan JL. Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine. Pediatrics. 2003 Apr;111(4 Pt 1):e376-81.

OBJECTIVE: To compare adolescents with migraine, unexplained profound chronic fatigue of >6 months duration, and normal school controls on measures of anxiety, depression, somatization, functional disability, and illness attribution. METHODS: Adolescents referred to Children's Hospital and Regional Medical Center for behavioral treatment of migraine (n = 179) or evaluation of chronic fatigue (n = 97) were compared with a group of healthy controls of similar age and sex from a middle school (n = 32). Subjects completed the Spielberger State-Trait Anxiety Inventory-Trait Form, the Children's Depression Inventory, the Childhood Somatization Inventory, and estimated the number of school days missed in the past 6 months because of illness. Migraine and fatigued subjects completed an illness attribution questionnaire. RESULTS: Subjects in the 3 groups were 56% to 70% female and ranged from 11 years old to 18 years old with a mean age of 14.0 +/- 2.0. Forty-six of the 97 chronically fatigued adolescents met 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CDC-CFS), while 51 had idiopathic chronic fatigue syndrome (I-CFS) that did not meet full CDC criteria. Adolescents with migraine had significantly higher anxiety scores than those with I-CFS or controls and higher somatization scores than controls. Adolescents with CDC-CFS had significantly higher anxiety scores than those with I-CFS or controls, and higher depression and somatization scores than all other groups. There were significant differences between all groups for school days missed with CDC-CFS more than I-CFS more than migraine more than controls. Parents of adolescents with unexplained I-CFS had significantly lower attribution scores relating illness to possible psychological or stress factors than parents of adolescents with CDC-CFS or migraine. CONCLUSIONS: Adolescents referred to an academic center for evaluation of unexplained chronic fatigue had greater rates of school absenteeism than adolescents with migraine or healthy controls. Those meeting CDC-CFS criteria had higher anxiety scores than controls and higher depression and somatization scores than migraineurs or controls. Parents of adolescents with I-CFS were less likely to endorse psychological factors as possibly contributing to their symptoms than parents of adolescents with CDC-CFS or

migraine.

8142. Torsheim T, Aaroe LE, Wold B. School-related stress, social support, and distress: prospective analysis of reciprocal and multilevel relationships. Scand J Psychol. 2003 Apr;44(2):153-9.

This three-wave prospective study investigated the reciprocal relationships among school-related stress, school-related social support, and distress in a cohort of 767 secondary school students (mean age 13.9 years). Stress, support, and distress were measured at three occasions with six-month lags between. Reciprocal relationships were analyzed with multivariate multilevel modeling (MLwiN). Each of the three factors at baseline predicted change in one or two of the other factors at subsequent measurements, indicating a complex pattern of reciprocal relationships among stress, support, and distress across time. A high level of distress at baseline predicted a lower level of support and a higher level of stress six months later. High levels of stress at baseline predicted a higher level of distress and a lower level of support 12 months later. The results are consistent with a transactional and dynamic model of stress, support, and distress, and indicate the need to view school-related stress, support, and distress as mutually dependent factors.

8143. Tselebis A, Papaleftheris E, Balis E, Theotoka I, Ilias I. Smoking related to anxiety and depression in Greek medical staff. Psychol Rep. 2003 Apr;92(2):529-32.

Heart Disease:

8144. Aggeli C, Stefanadis C, Bonou M, Pitsavos C, Theocharis C, Roussakis G, Chatzos C, Brili S, Toutouzas P. Prediction of functional recovery of hibernating myocardium using harmonic power Doppler imaging and dobutamine stress echocardiography in patients with coronary artery disease. Am J Cardiol. 2003 Jun 15;91(12):1415-20.

The aim of this study was to compare the accuracy of harmonic power Doppler imaging (HPDI) and dobutamine stress echocardiography (DSE) in predicting recovery of myocardial function after bypass surgery. HPDI using triggering imaging with the administration of Levovist (Shering AG, Berlin, Germany) and DSE were performed in 34 patients (mean age 64 +/- 5 years) with left ventricular dysfunction. A repeat echocardiogram at rest was performed 3 months after revascularization. Of the 408 revascularized dysfunctional segments, 188 (45%) improved on the repeat echocardiogram. HPDI exhibited overall similar sensitivity (88% vs 87%) and accuracy (74% vs 79%) but lower specificity (61% vs 72%, p<0.05) compared with DSE for predicting recovery of myocardial function. Only delayed opacification at the 1:8 triggering point, demonstrated in 62% of viable segments, exhibited higher sensitivity (63%) and positive (58%) and negative (66%) predictive values than early opacification at 1:4 (25%, p<0.001; 35%, p<0.001; and 49%, p<0.001, respectively) in predicting functional recovery. The presence of contrast enhancement within the revascularized area resulted in a significant improvement after revascularization in wall motion score index and ejection fraction compared with areas with residual contrast defect (1.9 +/- 0.3 vs 2.3 +/- 0.3, p<0.01; 36 +/- 6% vs 29 +/- 5%, p<0.01, respectively). Significant correlations were observed between the contrast score index and the follow-up wall motion score index (r = -0.67) and between the contrast score index and the follow-up ejection fraction change (r = 0.65). Triggered HPDI has high sensitivity in detecting hibernating myocardium and can accurately predict the potential for recovery of ischemic left ventricular dysfunction 3 months after revascularization.

8145. Berman DS, Kang X, Hayes SW, Friedman JD, Cohen I, Abidov A, Shaw LJ, Amanullah AM, Germano G, Hachamovitch R. Adenosine myocardial perfusion single-photon emission computed tomography in women compared with men. Impact of diabetes mellitus on incremental prognostic value and effect on patient management. J Am Coll Cardiol. 2003 Apr 2;41(7):1125-33.

OBJECTIVES: This study was designed to assess the incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography (MPS) in women versus men, and to explore the prognostic impact of diabetes mellitus. BACKGROUND: Limited data are available regarding the incremental value of adenosine stress MPS for the prediction of cardiac death in women versus men and the impact of diabetes mellitus on post-adenosine MPS outcomes.Of 6,173 consecutive patients who underwent rest thallium-201/adenosine technetium-99m sestamibi MPS, 254 (4.1%) were lost to follow-up, and 586 with early revascularization < or = 60 days after MPS were censored, leaving 2,656 women and 2,677 men. RESULTS: Women had significantly smaller adenosine stress, rest, and reversible defects than men. During 27.0 +/- 8.8 month follow-up, cardiac death rates were lower in women than men (2.0%/year vs. 2.7%/year, respectively, p < 0.05). Before and after risk adjustment, cardiac death risk increased significantly in both men and women as a function of MPS results. Multivariable models revealed that MPS results provided incremental prognostic value over pre-scan data for the prediction of cardiac death in both genders. Also, while comparative unadjusted rates of early (< or =60 days post-test) coronary angiography (17% vs. 23%) and revascularization (8% vs. 12%) were significantly lower in women (p < 0.05), after adjusting for MPS, these rates were similar in men and women. Importantly, diabetic women had a significantly greater risk of cardiac death compared with other patients. Also, after risk adjustment, patients with insulin-dependent diabetes mellitus (IDDM) had higher risk of cardiac death for any MPS result than patients with non-insulin-dependent diabetes mellitus. CONCLUSION: The findings suggest that adenosine MPS has comparable incremental value for prediction of cardiac death in women and men and that MPS is appropriately influencing subsequent invasive management decisions in both genders. Diabetic women and patients with IDDM appear to have greater risk of cardiac death than other patients for any MPS result.

8146. Cortigiani L, Coletta C, Bigi R, Amici E, Desideri A, Odoguardi L. Clinical, exercise electrocardiographic, and pharmacologic stress echocardiographic findings for risk stratification of hypertensive patients with chest pain. Am J Cardiol. 2003 Apr 15;91(8):941-5.

Exercise electrocardiography (ECG) is of limited usefulness in hypertensive patients, whereas pharmacologic stress echocardiography can provide diagnostic and prognostic information. The aim of this study was to compare the prognostic value of clinical data, exercise ECG, and pharmacologic stress echocardiography in hypertensive patients with chest pain and to identify the best strategy for their risk stratification. Three hundred sixty-seven hypertensive patients (189 men, age 61 +/- 9 years) with chest pain of unknown origin underwent exercise ECG and pharmacologic stress echocardiography (237 with dipyridamole and 130 with dobutamine) and were followed up for 31 +/- 24 months. Positive exercise ECG (ST-segment shift of > or =1 mm at 80 ms after the J point) and stress echocardiography (new wall motion abnormalities) were found in 130 (35%) and 86 (23%) patients, respectively. During follow-up, there were 13 deaths and 16 myocardial infarctions. Additionally, 43 patients underwent coronary revascularization and were censored accordingly. Of 12 clinical, electrocardiographic, and echocardiographic variables analyzed, a positive result of stress echocardiography was the only multivariate predictor of either death (hazard ratio [HR] 4.7, 95% confidence interval [CI] 1.5 to 14.5, p = 0.007) or hard events (death, myocardial infarction) (HR 4.1, 95% CI 1.8 to 9.3, p = 0.0009). Using an interactive stepwise procedure, stress echocardiography provided additional prognostic information to clinical evaluation and exercise ECG. However, the negative predictive value of the 2 tests was similarly (p = NS) high in assessing 4-year event-free survival. In conclusion, a negative exercise electrocardiographic test identifies low-risk hypertensive patients with chest pain and should be the first-line approach for risk stratification. In contrast, positive exercise ECG is unable to distinguish between patients with different levels of risk. In this case, stress echocardiography provides strong and incremental prognostic power over clinical and exercise electrocardiographic data.

8147. Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel JL, Hasenfuss G, Shah AM. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol. 2003 Jun 18;41(12):2164-71.

OBJECTIVES: This study was designed to investigate whether nicotinamide adenine dinucleotide 3-phosphate (reduced form) (NADPH) oxidase is expressed in the human heart and whether it contributes to reactive oxygen species (ROS) production in heart failure. BACKGROUND: A phagocyte-type NADPH oxidase complex is a major source of ROS in the vasculature and is implicated in the pathophysiology of hypertension and atherosclerosis. An increase in myocardial oxidative stress due to excessive production of ROS may be involved in the pathophysiology of congestive heart failure. Recent studies have suggested an important role for myocardial NADPH oxidase in experimental models of cardiac disease. However, it is unknown whether NADPH oxidase is expressed in the human myocardium or if it has any role in human heart failure. METHODS: Myocardium of explanted nonfailing (n = 9) and end-stage failing (n = 13) hearts was studied for the expression of NADPH oxidase subunits and oxidase activity. RESULTS: The NADPH oxidase subunits p22(phox), gp91(phox), p67(phox), and p47(phox) were all expressed at messenger ribonucleic acid and protein level in cardiomyocytes of both nonfailing and failing hearts. NADPH oxidase activity was significantly increased in end-stage failing versus nonfailing myocardium (5.86 +/- 0.41 vs. 3.72 +/- 0.39 arbitrary units; p < 0.01). The overall level of oxidase subunit expression was unaltered in failing compared with nonfailing hearts. However, there was increased translocation of the regulatory subunit, p47(phox), to myocyte membranes in failing myocardium. CONCLUSIONS: This is the first report of the presence of NADPH oxidase in human myocardium. The increase in NADPH oxidase activity in the failing heart may be important in the pathophysiology of cardiac dysfunction by contributing to increased oxidative stress.

8148. Hui L, Leung MP, Ha SY, Chau AK, Cheung YF. Early detection of left ventricular dysfunction in patients with beta thalassaemia major by dobutamine stress echocardiography. Heart. 2003 Jun;89(6):669-70. No abstract.

8149. Koyama J, Ray-Sequin PA, Falk RH. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation. 2003 May 20;107(19):2446-52. Epub 2003 May 12.

BACKGROUND: AL amyloidosis with heart failure is associated with decreased longitudinal myocardial contraction measured by pulsed tissue Doppler imaging. We sought to clarify whether new modalities of myocardial strain Doppler (change in length per unit length) or strain rate (the temporal derivative of strain) were more sensitive than tissue Doppler and could detect early regional myocardial dysfunction before the onset of congestive heart failure (CHF) in patients with AL (primary) amyloidosis. METHODS AND RESULTS: Ninety-seven biopsy-proven patients with AL amyloidosis were divided into 3 groups. Group 1 patients had no cardiac involvement (n=36), group 2 had heart involvement but no CHF (n=32), and group 3 had heart involvement and CHF (n=29). All patients underwent tissue velocity (TV) imaging, strain, and strain rate imaging (SR) at the basal, mid, and apical ventricle in 2 apical views. With the use of TV, differences in systolic function were only apparent between group 3 (basal mean value, 3.0+/-1.1 cm/s) and groups 1 and 2 (5.0+/-1.3 and 4.6+/-1.2 cm/s, respectively). In contrast, basal peak systolic SR (l/s) showed significant differences among all 3 groups (-2.0+/-0.4, -1.55+/-0.6, and -0.76+/-0.3 for groups 1 to 3, respectively. P<0.01). Basal strain also demonstrated statistically significant differences among the groups (-19+/-4%, -15+/-4.5%, and -8.0+/-5%; P<0.01). CONCLUSIONS: Cardiac amyloidosis is characterized by an early impairment in systolic function at a time when fractional shortening remains normal. This abnormality precedes the onset of CHF and can be detected by strain and SR but is not apparent by TV imaging.

8150. Lancellotti P, Hoffer EP, Pierard LA. Detection and clinical usefulness of a biphasic response during exercise echocardiography early after myocardial infarction. J Am Coll Cardiol. 2003 Apr 2;41(7):1142-7.

OBJECTIVE: The aim of this study was to determine the accuracy of exercise echocardiography (EE) for detecting infarct-related artery (IRA) stenosis and predicting functional recovery early after acute myocardial infarction (AMI). BACKGROUND: Dobutamine stress echocardiography is widely used for identifying jeopardized myocardium. The clinical usefulness of a biphasic response detected during EE has never been investigated. METHODS: A total of 114 consecutive patients with a first AMI and > or = 2 dyssynergic segments in the infarct-related territory underwent semi-supine continuous EE 6 +/- 2 days after AMI. Quantitative coronary angiography was performed in all patients after EE. A follow-up echocardiogram was obtained one month later. RESULTS: Ninety-seven patients had significant (> or = 50%) IRA stenosis, and 26 had multivessel disease. Residual ischemia was identified in 77 patients (biphasic response in 62 and worsening response in 15). The sensitivity and specificity of ischemia during EE for predicting IRA stenosis were 75% and 76%, respectively. The sensitivity of a biphasic response was higher than the sensitivity of a worsening response (61% vs. 14%, p < 0.0001). Wall motion abnormalities induced in other vascular territories were specific (97%) and moderately sensitive (62%) for the detection of multivessel disease. Functional recovery was observed in 75 patients. Two independent variables predicted contractile recovery: contractile reserve during EE (p < 0.0001) and elective angioplasty of the IRA (p = 0.002). A biphasic response, but not sustained improvement, predicted reversible dysfunction (73% vs. 9%, p < 0.0001). CONCLUSIONS: A biphasic response can be detected during exercise. Exercise echocardiography is an accurate tool for detecting IRA stenosis and predicting functional improvement early after AMI.

8151. Latimer DC, Roth BJ, Parker KK. Analytical model for predicting mechanotransduction effects in engineered cardiac tissue. Tissue Eng. 2003 Apr;9(2):283-9.

Mechanochemical and mechanoelectrical signaling is imperative for cardiac organogenesis and underlies pathophysiological events. New techniques for engineering cardiac tissue allow unprecedented means of modeling these phenomena in vitro. However, experimental design is often hampered by a lack of models that can be adapted to the ideal conditions these methods allow. To address these deficiencies, we developed a mathematical model to calculate the distribution of stress and strain in fibrous cardiac tissue. The fluid-fiber-collagen model characterizes the mechanical behavior of cardiac tissue and is solved analytically for the distributions of stress and strain along the myocardial fibers. An example application of the model is presented: modeling the distribution of strains in the vicinity of an ischemic region. The ischemic region is stretched during systole, as has been shown in previous one-dimensional models. Our model predicts a complex distribution of stretch in the border zone surrounding the ischemic region and in nonischemic regions surrounding the border zone. These strain patterns may predict patterns of mechanochemical coupling that results in localized fibrosis, altered gene expression, or the mechanoelectrical signaling events that potentiate cardiac arrhythmias.

8152. Leesar MA, Abdul-Baki T, Akkus NI, Sharma A, Kannan T, Bolli R. Use of fractional flow reserve versus stress perfusion scintigraphy after unstable angina. Effect on duration of hospitalization, cost, procedural characteristics, and clinical outcome. J Am Coll Cardiol. 2003 Apr 2;41(7):1115-21.

OBJECTIVES: The present study sought to determine the value of fractional flow reserve (FFR) compared with stress perfusion scintigraphy (SPS) in patients with recent unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: Fractional flow reserve, an invasive index of stenosis severity, is a reliable surrogate for SPS in patients with normal left ventricular function. An FFR > or = 0.75 can distinguish patients after myocardial infarction (MI) with a positive SPS from those with a negative SPS. However, the use of FFR has not been investigated after UA/NSTEMI. METHODS: Seventy patients who had recent UA/NSTEMI and an intermediate single-vessel stenosis were randomized to either SPS (n = 35) or FFR (n = 35). Patients in the SPS group were discharged if the SPS revealed no ischemia, whereas those in the FFR group were discharged if the FFR was > or = 0.75. Patients with a positive SPS and those with an FFR <0.75 underwent percutaneous transluminal coronary angioplasty. The use of FFR markedly reduced the duration and cost of hospitalization compared with SPS (11 +/- 2 h vs. 49 +/- 5 h [-77%], p < 0.001; and 1,329 US dollars +/- 44 US dollars vs. 2,113 US dollars +/- 120 US dollars, respectively, p < 0.05). There were no significant differences in procedure time, radiation exposure time, or event rates during follow-up, including death, MI, or revascularization. CONCLUSIONS: These data indicate that: 1) the use of FFR in patients with recent UA/NSTEMI markedly reduces the duration and cost of hospitalization compared with SPS; and 2) these benefits are not associated with an increase in procedure time, radiation exposure time, or clinical event rates.

8153. Logar CM, Herzog CA, Beddhu S. Diagnosis and therapy of coronary artery disease in renal failure, end-stage renal disease, and renal transplant populations. Am J Med Sci. 2003 Apr;325(4):214-27. Review.

Even though cardiovascular disease is the leading cause of death in patients with CRF and end-stage renal disease (ESRD), ill-conceived notions have led to therapeutic nihilism as the predominant strategy in the management of cardiovascular disease in these populations. The recent data clearly support the application of proven interventions in the general population, such as angiotensin-converting enzyme inhibitors and statins to patients with CRF and ESRD. The advances in coronary stents and intracoronary irradiation have decreased the restenosis rates in renal failure patients. Coronary artery bypass with internal mammary graft might be the procedure of choice for coronary revascularization in these patients. The role of screening for asymptomatic coronary disease is established as a pretransplant procedure, but it is unclear whether this will be applicable to all patients with ESRD. Future studies need to focus on unraveling the mechanisms by which uremia leads to increased cardiovascular events to design optimal therapies targeted toward these mechanisms and improve cardiovascular outcomes.

8154. Malfatto G, Facchini M, Zaza A. Characterization of the non-linear rate-dependency of QT interval in humans. Europace. 2003 Apr;5(2):163-70.

AIMS: Repolarization has rate-dependent and rate-independent components. A function considering such components separately was validated in canine Purkinje fibres and applied to the QT/RR relation in humans. METHODS AND RESULTS: Action potential duration (APD) was measured in Purkinje fibres during steady-state pacing at different cycle lengths (CL) and after prolonged quiescence (APD(0)). The APD/CL relationship was expressed by this function: APD=APD(max)(*)CL(S)/(CL(50)(S)+CL(S)), where APD(max) (APD extrapolated at infinite CL) is a rate-independent measure of repolarization, CL(50) (CL at which 50% of APD(max) is achieved) and S evaluates the rate dependency of APD. The same function was used to fit the QT/RR relation in 46 normal subjects (20 males, 26 females) and in 7 amiodarone-treated subjects undergoing a bicycle stress test. RR and QT (V(5)) were measured at the end of each load step; QT(c) (Bazett's formula) was obtained at rest. The APD/CL and QT/RR relations were equally well expressed by the function with high correlation coefficients (R>or=0.90). In Purkinje fibres, APD(max) was 461+/-37 ms, CL(50) was 394+/-54 ms and S was 0.98+/-0.11. APD(max) and APD(0) correlated (R=0.96) and were similar. The corresponding values in humans were: QT(max) 432+/-63 ms, RR(50) 345+/-60 ms and S 2.6+/-0.8. While QT(c) and QT(max) were longer in females, RR(50) and S were similar between genders. Amiodarone increased QT(c), QT(max) and RR(50) and decreased S. In QT(max) and QT(c) distributions generated by pooling data from treated and untreated subjects, 86% of treated subjects were correctly identified by QT(max) and 28% by QT(c). CONCLUSIONS: Canine and human repolarization showed a saturating dependency on cycle length, described by the proposed function. Gender and amiodarone independently affected QT(max), RR(50) and S: therefore they might reflect specific ionic mechanisms. Finally, QT(max) identified drug-induced repolarization abnormalities in individual subjects better than QT(c). Copyright 2003 The European Society of Cardiology. Published by Elsevier Science Ltd.

8155. Oh H, Wang SC, Prahash A, Sano M, Moravec CS, Taffet GE, Michael LH, Youker KA, Entman ML, Schneider MD. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5378-83. Epub 2003 Apr 17.

The "postmitotic" phenotype in adult cardiac muscle exhibits similarities to replicative senescence more generally and constitutes a barrier to effective restorative growth in heart disease. Telomere dysfunction is implicated in senescence and apoptotic signaling but its potential role in heart disorders is unknown. Here, we report that cardiac apoptosis in human heart failure is associated specifically with defective expression of the telomere repeat- binding factor TRF2, telomere shortening, and activation of the DNA damage checkpoint kinase, Chk2. In cultured cardiomyocytes, interference with either TRF2 function or expression triggered telomere erosion and apoptosis, indicating that cell death can occur via this pathway even in postmitotic, noncycling cells; conversely, exogenous TRF2 conferred protection from oxidative stress. In vivo, mechanical stress was sufficient to down-regulate TRF2, shorten telomeres, and activate Chk2 in mouse myocardium, and transgenic expression of telomerase reverse transcriptase conferred protection from all three responses. Together, these data suggest that apoptosis in chronic heart failure is mediated in part by telomere dysfunction and suggest an essential role for TRF2 even in postmitotic cells.

8156. Prichard S. Risk factors for coronary artery disease in patients with renal failure. Am J Med Sci. 2003 Apr;325(4):209-13. Review.

Cardiovascular mortality is markedly increased in patients with end-stage renal disease (ESRD), particularly those receiving dialysis. Coronary artery disease is the most important cause of death in these patients. As in the general population, older age, male gender, and the postmenopausal state in women are cardiovascular risk factors in patients with ESRD. However, hypertension, diabetes mellitus, and dyslipidemia, known to promote cardiovascular disease in the general population, are particularly likely to do so in patients with ESRD because of their high prevalence in this population. In addition, nontraditional cardiovascular risk factors, such as hyperhomocystinemia, inflammation, elevated calcium x phosphate product, endothelial dysfunction, and oxidant stress, occur frequently in patients with ESRD. Vigorous treatment of modifiable cardiovascular risk factors has reduced cardiovascular risk in patients without ESRD. The extent to which such risk factor modification would alter cardiovascular risk in ESRD remains uncertain.

8157. Qing M, Schumacher K, Heise R, Woltje M, Vazquez-Jimenez JF, Richter T, Arranda-Carrero M, Hess J, von Bernuth G, Seghaye MC. Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects. J Am Coll Cardiol. 2003 Jun 18;41(12):2266-74.

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group.

8158. Samady H, Liu YH, Choi CJ, Ragosta M, Pfau SE, Cleman MW, Powers ER, Kramer CM, Wackers FJ, Beller GA, Watson DD. Electromechanical mapping for detecting myocardial viability and ischemia in patients with severe ischemic cardiomyopathy. Am J Cardiol. 2003 Apr 1;91(7):807-11.

This study was designed to evaluate several electromechanical mapping parameters for assessment of myocardial viability and inducible ischemia as defined by dipyridamole single-photon emission computed tomographic (SPECT) imaging at rest in patients with severe ischemic cardiomyopathy. Unipolar voltage, normalized unipolar voltage, bipolar voltage, and fragmentation were compared with tracer uptake at rest and reversibility on stress or rest quantitative technetium-99m sestamibi SPECT imaging in 32 patients with severe ischemic cardiomyopathy (left ventricular ejection fraction 0.24 +/- 0.08). In dysfunctional myocardial segments, logistic regression showed unipolar voltage, normalized unipolar voltage, and bipolar voltage to be predictive of viable myocardium (> or = 60% tracer uptake at rest) and was significantly higher in viable than in nonviable segments (p <0.01). A unipolar voltage of > or = 7.1 mV was the best predictor of viable myocardium. In dysfunctional viable segments, unipolar voltage was significantly higher in reversible than in fixed segments (p <0.001), and a unipolar voltage of > or = 8.5 mV had optimal power for identifying reversibility on dipyridamole SPECT imaging. We conclude that in patients with severe ischemic cardiomyopathy, unipolar voltage can identify viable from nonviable myocardium and reversible from fixed viable defects as defined by dipyridamole technetium-99m sestamibi SPECT imaging.

8159. Schinkel AF, Bax JJ, Geleijnse ML, Boersma E, Elhendy A, Roelandt JR, Poldermans D. Noninvasive evaluation of ischaemic heart disease: myocardial perfusion imaging or stress echocardiography? Eur Heart J. 2003 May;24(9):789-800. Review. No abstract.

8160. Shastry S, Hayden MR, Lucchesi PA, Tyagi SC. Matrix metalloproteinase in left ventricular remodeling and heart failure. Curr Cardiol Rep. 2003 May;5(3):200-4. Review.

Accumulation of oxidized matrix between the endothelium and cardiac muscle, and endocardial endothelial dysfunction, are the hallmarks of congestive heart failure. The induction of oxidative stress, decrease in endothelial cell density, activation of matrix and disintegrin metalloproteinase, collagenolysis, and repression of cardiac inhibitor of metalloproteinase (CIMP) are associated with deposition of oxidized matrix. Studies that employ CIMP as genetic or proteomic therapeutic agent may improve the heart's response to nitric oxide donors. Identification of major players involved in the control of oxidative and proteolytic stresses that ameliorate matrix deposition by integrin shading will help to develop strategies to prevent congestive heart failure.

8161. Shoyeb A, Bokhari S, Sullivan J, Hurley E, Miesner B, Pia R, Giglio J, Sayan OR, Soto L, Chiadika S, LaMarca C, Rabbani LE, Bergmann SR. Value of definitive diagnostic testing in the evaluation of patients presenting to the emergency department with chest pain. Am J Cardiol. 2003 Jun 15;91(12):1410-4.

The optimal diagnostic evaluation of patients presenting to the emergency department (ED) with chest pain but without myocardial infarction or unstable angina is controversial. We performed a prospective, nonrandomized, observational study of 1,195 consecutive patients presenting to the ED with chest pain but who had normal or nondiagnostic electrocardiograms and negative cardiac biomarkers. Patients (mean +/- SD age 61 +/- 15 years; 55% women) were admitted to the hospital and a standard protocol for evaluation and treatment was suggested. The use of stress myocardial perfusion imaging (MPI) or cardiac catheterization during their index hospitalization, and the 3-month incidence of coronary angiography, percutaneous cardiac intervention, coronary artery bypass surgery, re-presentation to our institution's ED for chest pain, myocardial infarction, or death were followed. Five hundred nine of 1,195 patients (43%) underwent provocative stress MPI during their index hospitalization; 37% had perfusion defects (predominantly ischemia). Fifty-six of 1,195 patients (4%) underwent cardiac catheterization without stress MPI for their primary diagnostic evaluation. Six hundred thirty of 1,195 patients (53%) had neither MPI or cardiac catheterization during their index hospitalization. During the 3-month follow-up period, patients with a normal stress perfusion study during their index hospitalization had fewer return visits (4%) compared with patients with abnormal perfusion studies (19%), those who underwent catheterization directly (16%), or patients with no initial diagnostic evaluation (15%) (p <0.001). In addition, patients who had a diagnostic evaluation during their index hospitalization had a lower incidence of either acute myocardial infarction (0.9% vs 2.1%) or death (0.4% vs 3.0%, p <0.001) in the 3-month follow-up period. Accordingly, we strongly advocate provocative stress MPI early after presentation for chest pain in all patients with risk factors for coronary artery disease.

8162. Zhao H, Miller M, Pfeiffer K, Buras JA, Stahl GL. Anoxia and reoxygenation of human endothelial cells decrease ceramide glucosyltransferase expression and activates caspases. FASEB J. 2003 Apr;17(6):723-4. Epub 2003 Feb 05.

Endothelial oxidative stress induces cellular activation and sometimes death. Endothelial death can occur via necrosis or apoptosis. Understanding the mechanisms involved in cellular activation and death may lead to therapeutics designed to increase death or preserve cellular function. In the present study, brief periods of anoxia (3 h) followed by varying lengths of reoxygenation (0-5 h) lead to a time-dependent increase in human umbilical vein endothelial cell (HUVEC) caspase activity. Furthermore, ROCK-1 cleavage, which is dependent on caspase-3 activity, was also increased in cells undergoing oxidative stress compared with normoxic cells. Microarray data demonstrated that glucosylceramide synthase (GCS; glucosylceramide transferase), but not acid sphingomyelinase, was modulated by anoxia and reoxygenation. We confirmed that GCS mRNA and protein expression were significantly decreased in a time-dependent fashion following oxidative stress by real-time polymerase chain reaction and Western blot, respectively. Treatment of normoxic cells with the GCS-specific inhibitor, D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), increased caspase activity to the same degree as cells undergoing oxidative stress. Fumonisin B1, the N-acyl-sphinganine dehydrogenase (e.g., ceramide synthase) inhibitor significantly attenuated caspase activity in HUVECs undergoing oxidative stress. These data suggest that alterations in GCS expression following brief periods of oxidative stress in human endothelial cells lead to increased caspase activity.

Hypertension:

8163. Casanueva E, Viteri FE. Iron and oxidative stress in pregnancy. J Nutr. 2003 May;133(5 Suppl 2):1700S-1708S. Review.

Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. Transitional metals, especially iron, which is particularly abundant in the placenta, are important in the production of free radicals. Protective mechanisms against free radical generation and damage increase throughout pregnancy and protect the fetus, which, however, is subjected to a degree of oxidative stress. Oxidative stress peaks by the second trimester of pregnancy, ending what appears to be a vulnerable period for fetal health and gestational progress. Conditions restricted to pregnancy, such as gestational hypertension, insulin resistance and diabetes, exhibit exaggerated indications of free radical damage. Antioxidants as well as avoidance of iron excess ameliorate maternal and early fetal damage. In rats both iron deficiency and excess result in free radical mitochondrial damage. Estimates of gestational iron requirements and of the proportion of iron absorbed from different iron supplemental doses suggest that with present supplementation schemes the intestinal mucosal cells are constantly exposed to unabsorbed iron excess and oxidative stress. Unpublished work carried out in Mexico City with nonanemic women at midpregnancy indicates that 60 mg/d of iron increases the risk of hemoconcentration, low birth weight and premature birth and produces a progressive decline in plasma copper. These risks are not observed in women supplemented with 120 mg iron once or twice per week. Studies on the influence of iron supplementation schemes on oxidative stress are needed.

8164. Cracowski JL, Baguet JP. Isoprostanes: are they more than physiopathological biomarkers of lipid peroxidation? Circulation. 2003 Jun 24;107(24):e222; author reply e222. No abstract.

8165. Redon J, Oliva MR, Tormos C, Giner V, Chaves J, Iradi A, Saez GT. Antioxidant activities and oxidative stress byproducts in human hypertension. Hypertension. 2003 May;41(5):1096-101. Epub 2003 Apr 21.

The objective was to study oxidative status, antioxidant activities, and reactive oxygen species byproducts in whole blood and mononuclear peripherals cells and their relationship with blood pressure. Sixty-six hypertensive patients and 16 normotensive volunteers as a control group were studied. In both, whole blood and peripheral mononuclear cells oxidized/reduced glutathione ratio and malondialdehyde was significantly higher, and the activity of superoxide dismutase, catalase, and glutathione peroxidase was significantly lower in hypertensive patients when compared with normal subjects. The content of damaged base 8-oxo-2'-deoxyguanosine in nuclear and mitochondrial deoxyribonucleoproteins of hypertensive subjects was also significantly higher than that of the normotensive control subjects. No differences in these measurements were found among hypertensive subjects grouped in tertiles of 24-hour average mean blood pressure or between "white-coat" and established hypertensive subjects. Furthermore, no relationship was observed between the average of 24-hour mean blood pressure and oxidized/reduced glutathione ratio, reactive oxygen species byproducts, malondialdehide, or genomic 8-oxo-2'-deoxyguanosine. In whole blood and in mononuclear cells from hypertensive subjects, there was an increase in oxidative stress and a reduction in the activity of antioxidant mechanisms that appeared to be independent of the blood pressure values.

8166. Taddei S, Virdis A, Ghiadoni L, Versari D, Salvetti G, Magagna A, Salvetti A. Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. Hypertension. 2003 Apr;41(4):950-5. Epub 2003 Mar 17.

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxidative stress-induced nitric oxide (NO) breakdown and compensatory production of a hyperpolarizing factor. To test whether calcium antagonist treatment can restore NO availability and prevent hyperpolarization through antioxidant properties, in 15 healthy subjects and 15 patients with essential hypertension, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial bradykinin (5, 15, 50 ng/100 mL per minute), an endothelium-dependent vasodilator, in basal conditions, during infusion of NG-monomethyl-l-arginine (L-NMMA, 100 microg/100 mL per minute), an NO-synthase inhibitor, and ouabain (0.72 microg/100 mL per minute), an Na+-K+ ATPase inhibitor to prevent hyperpolarization. These infusions were repeated in the presence of the antioxidant vitamin C (8 mg/100 mL/min). The response to sodium nitroprusside was also evaluated. In controls, vasodilation to bradykinin was inhibited by L-NMMA and remained unchanged by ouabain or vitamin C. In hypertensive patients, vasodilation to bradykinin was blunted and resistant to L-NMMA but sensitive to ouabain. Vitamin C increased the response to bradykinin and restored the inhibiting effect of L-NMMA while preventing the effect of ouabain. In hypertensive patients, infusions were repeated after 3-month treatment with lercanidipine (10 to 20 mg daily). Lercanidipine decreased plasma lipoperoxides, isoprostanes, and malondialdehyde and increased plasma antioxidant capacity. Moreover, lercanidipine increased the vasodilation to bradykinin and restored the inhibiting effect of L-NMMA on bradykinin-induced vasodilation while preventing the effect of ouabain. Finally, vitamin C no longer exerted its facilitating activity. These results indicate that in essential hypertension, lercanidipine increases endothelium-dependent vasodilation by restoring NO availability and preventing hyperpolarization, an effect probably determined by antioxidant activity.

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