Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:


     Back to reference

January 2003 

  6221.      Aires Franca S, Ribeiro Carvalho CR. Effectiveness, safety and tolerability of gatifloxacin, a new 8-methoxyfluoroquinolone, in the treatment of outpatients with community-acquired pneumonia: a brazilian study. Braz J Infect Dis. 2002 Aug;6(4):157-63.


Objectives: Evaluation of the effectiveness, safety and tolerability of gatifloxacin in the treatment of outpatients with community-acquired pneumonia (CAP). Study Design: A prospective, multicenter, non-comparative clinical study carried out in Brazil. Voluntary, unpaid physician participation contributed to an unbiased study design. Patients: Adult outpatients with clinical diagnosis of CAP. Regimen: Gatifloxacin, 400 mg PO once daily for 7 to 14 days. Study Procedures: Initial clinical assessment, at the first day of gatifloxacin therapy; final evaluation after 7 to 14 days of treatment. Results: According to the physicians  assessments 97.3% of patients were cured or improved after gatifloxacin treatment. The incidence of adverse events was low and the most commonly reported events were nausea and dyspepsia. Conclusions: Gatifloxacin, 400 mg PO once daily for 7 to 14 days, is effective and safe in the treatment of patients with CAP.


6222.  Akira M, Ishikawa H, Yamamoto S. Drug-induced pneumonitis: thin-section CT findings in 60 patients. Radiology. 2002 Sep;224(3):852-60.


PURPOSE: To describe thin-section computed tomographic (CT) findings in patients with drug-induced pneumonitis, to compare these CT findings, and to correlate them with arterial oxygen tension level. MATERIALS AND METHODS: Thin-section CT scans obtained in 60 patients with drug-induced pneumonitis were evaluated retrospectively. The patients had 31 cases of antineoplastic agent-induced pneumonitis and 29 cases of nonneoplastic agent-induced pneumonitis (antibiotic agent, 20 cases; herbal medicine [sho-saiko-to], four cases; antirheumatic agent, three cases; phenytoin, one case; disodium cromoglycate, one case). CT scans were reviewed by two chest radiologists in consensus. Correlation between arterial oxygen tension level and the extent of disease at CT was available in 21 patients. These two factors were compared by using the Spearman rank correlation coefficient. RESULTS: The predominant findings in antineoplastic agent-induced pneumonitis were diffuse or multifocal ground-glass opacities with intralobular interstitial thickening. The predominant CT findings in antibiotic agent-induced pneumonitis were patchy ground-glass opacities with centrilobular opacities and interlobular septal lines. The predominant CT findings in herbal medicine-induced pneumonitis were diffuse ground-glass opacities with patchy consolidation. Interlobular septal lines and centrilobular opacities were observed more frequently in antibiotic agent-induced pneumonitis, and intralobular interstitial thickening was observed more frequently in antineoplastic agent-induced pneumonitis. A significant correlation was established between arterial oxygen tension level and extent of disease at CT (r = -0.84, P <.05). CONCLUSION: In addition to ground-glass opacities and interlobular septal lines, the most common thin-section CT findings were intralobular interstitial thickening, observed in antineoplastic agent-induced pneumonitis, and centrilobular opacities, observed in antibiotic-induced pneumonitis. Copyright RSNA, 2002

6223.  Barry SM, Lipman MC, Deery AR, Johnson MA, Janossy G. Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV-infected subjects. HIV Med. 2002 Jul;3(3):207-11.


An HIV-infected man presented with a pneumonic illness following an episode of treated Pneumocystis carinii pneumonia (PCP). He had a rise in his CD4 count from 4 to 125 cells/microL on antiretroviral therapy prior to the onset of the second respiratory event. Bronchoalveolar lavage (BAL) revealed no pathogen, although a CD4 lymphocytosis in addition to a highly unusual population of rapidly proliferating CD8 cells was demonstrated. Following 2 weeks of steroid and anti-pneumocystis therapy, a repeat bronchoscopy demonstrated that the expression of these markers had returned to low values. This second respiratory illness, which may have arisen as a consequence of the regenerating immune response reacting to residual P. carinii antigen in the lung, is apparently not rare. When we reviewed our case notes, five further individuals were identified that had started antiretroviral therapy following an episode of PCP and subsequently developed a self-limiting pneumonitis for which no pathogen was identified on bronchoscopy.

6224.  Bennedsen M, Berthelsen L, Lind I. Performance of Three Microimmunofluorescence Assays for Detection of Chlamydia pneumoniae Immunoglobulin M, G, and A Antibodies. Clin Diagn Lab Immunol. 2002 Jul;9(4):833-9.


The microimmunofluorescence (MIF) test is considered the "gold standard" for laboratory diagnosis of acute and chronic Chlamydia pneumoniae infection. The performance of a MIF test based on C. pneumoniae antigen from Washington Research Foundation (WRF) was compared with those of assays from Labsystems (LAB) and MRL Diagnostics (MRL) by investigation of sera from three groups of patients: group I, 83 sera from 28 patients with atypical pneumonia; group II, 37 sera from 16 patients with acute C. pneumoniae or Chlamydia psittaci respiratory tract infection confirmed by PCR or culture; group III, 100 sera from 100 persons enrolled in the Copenhagen City Heart Study. The accordance among the results of the WRF assay and the two commercial assays was excellent for the immunoglobulin M (IgM) antibody detection rate (98%). The accordance in detection rates for IgG and IgA antibodies in sera from patients with acute infections was acceptable (87 and 88%), and in sera from group III, it was excellent (95 and 97%). The determinations of endpoint titers were reproducible with <1 dilution step difference for all three methods, except that the mean IgM antibody titer found by the LAB assay was almost 2 dilution steps higher than that found by the other two methods. Although the three assays use different C. pneumoniae strains as antigens, the detection rates and IgG and IgA endpoint titers were similar. The difference in endpoint titers of IgM antibodies is of no major concern, as the diagnosis of acute C. pneumoniae infection rests on the presence of IgM antibodies, not on their level.

6225.  Black SB, Shinefield HR, Ling S, Hansen J, Fireman B, Spring D, Noyes J, Lewis E, Ray P, Lee J, Hackell J. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect Dis J. 2002 Sep;21(9):810-5.


OBJECTIVE: To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children. METHODS: The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity. RESULTS: The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group. CONCLUSION: The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.


6226.  Brandt J, Wong C, Mihm S, Roberts J, Smith J, Brewer E, Thiagarajan R, Warady B. Invasive pneumococcal disease and hemolytic uremic syndrome. Pediatrics. 2002 Aug;110(2 Pt 1):371-6.


OBJECTIVE: Severe pneumococcal infections have been associated with hemolytic uremic syndrome (HUS), usually with a poor clinical outcome when compared with Escherichia coli O157 gastroenteritis-associated (D+) HUS. We examined our experience with 12 cases of Streptococcus pneumoniae-associated HUS (SP-HUS) and compare it with a cohort of diarrhea-associated HUS (D+ HUS). METHODS: A retrospective case survey compared 2 unrelated groups of HUS patients. Demographic factors, clinical indices of disease severity, and outcome were used to compare the 2 groups of HUS patients. RESULTS: Twelve children with SP-HUS were studied. Pneumococcal pneumonia with empyema was the most common precipitating illness (67%), pneumococcal meningitis was present in 17% of children, pneumonia with bacteremia in 8%, and both pneumonia and meningitis in 8%. SP-HUS patients were younger than D+ HUS patients (22.1 vs 49 months) and had more severe renal and hematologic disease than D+ HUS patients. Compared with D+ HUS patients, SP-HUS patients were more likely to require dialysis (75% vs 59%) and had a longer duration of hospitalization (33.2 vs 16.1 days) and duration of thrombocytopenia (11.6 vs 6.8 days). SP-HUS patients were also more likely to require platelet transfusions (83% vs 47%) and needed more platelet (4.7 vs 0.5) and packed red blood cell transfusions (7.8 vs 2.0). The 2 groups did not differ significantly in the incidence of extrarenal HUS complications. There were no deaths in either group. Seven patients have been seen for long-term follow-up; 2 developed end-stage renal disease, and 5 have normal renal function. CONCLUSIONS: HUS is a rare but severe complication of invasive pneumococcal infection. Although disseminated intravascular coagulation can also occur in these children, the treatment and follow-up may be different in the 2 conditions. Children with pneumococcal disease and severe hematologic or renal abnormalities should be investigated for evidence of HUS.


6227.  Caldera AE, Crespo GJ, Maraj S, Kotler M, Braitman LE, Eiger G. Electrocardiogram in Pneumocystis carinii pneumonia: can it be used as a prognostic variable? Crit Care Med. 2002 Jul;30(7):1425-8.


OBJECTIVE: Many prognostic variables have been studied in patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome (AIDS). The role of the electrocardiogram in this setting has not been previously evaluated. We analyzed the admission electrocardiogram in patients with Pneumocystis carinii pneumonia and AIDS in an attempt to identify electrocardiogram findings that could be associated with adverse clinical outcomes and worse prognostic variables. DESIGN: A retrospective medical chart review. SETTING: All confirmed cases of Pneumocystis carinii pneumonia in patients positive for human immunodeficiency virus admitted to Albert Einstein Medical Center from 1994 to 2000. METHODS: Patients were assigned increasing severity ranks based on the findings on the admission electrocardiogram (normal sinus rhythm, sinus tachycardia, and right ventricular strain pattern). Data were extracted regarding study outcomes (admission to intensive care unit, mechanical ventilation, and hospital mortality) and prognostic variables. MAIN RESULTS: Of the 40 study patients, 14 (35%) had normal sinus rhythm, 15 (37.5%) had sinus tachycardia, and 11 (27.5%) presented with signs of right ventricular strain. The number of admissions to the intensive care unit, use of mechanical ventilation, and hospital mortality rate all increased with the severity of the electrocardiogram findings (p < or =.03). The serum lactate dehydrogenase concentrations and the alveolar-arterial oxygen gradient both increased with the severity of the electrocardiogram findings (p < or =.02). CONCLUSION: Electrocardiogram findings of sinus tachycardia and right heart strain are common in Pneumocystis carinii pneumonia. These findings are associated with adverse clinical outcomes as well as worsening of prognostic variables. The electrocardiogram may be useful in predicting outcome in patients with Pneumocystis carinii pneumonia.

6228.  Endo S, Murayama F, Yamaguchi T, Yamamoto S, Otani S, Saito N, Sohara Y. Surgical considerations for pulmonary actinomycosis. Ann Thorac Surg. 2002 Jul;74(1):185-90.


BACKGROUND: Diagnosis and treatment of pulmonary actinomycosis is difficult without surgical intervention. METHODS: Thirteen patients (10 men, 3 women; mean age, 62 years) underwent pulmonary resection and were given a pathologic diagnosis of pulmonary actinomycosis at our institution between 1976 and 2001. To clarify when pulmonary actinomycosis should be suspected in patients and the role of surgical intervention, we reviewed preoperative clinical characteristics, computed tomography findings, surgical indication, operative procedure, postoperative clinical course, and outcome. RESULTS: Ten patients (77%) had poor oral hygiene. Twelve patients (92%) were symptomatic, and 10 patients (77%) had hemoptysis. The mean interval between radiographic identification of the abnormality and surgical intervention was 8 months (interquartile range, 3.25 to 8 months). Computed tomography findings in all cases included radiologic opacity with air bronchogram or a low attenuation area. Lung cancer was diagnosed initially because of computed tomography findings of spiculation or pleural indentation, and operation was required in 8 patients (62%). The others were diagnosed with chronic pneumonia, and surgical intervention became necessary because of recurrent hemoptysis or prolonged illness. Six patients underwent lobectomy; the others underwent partial resection or segmentectomy. Neither complication nor recurrence has occurred. CONCLUSIONS: When patients, particularly those with poor oral hygiene, show radiologic opacity with an air bronchogram or low attenuation area on the computed tomography scan, pulmonary actinomycosis should be considered and penicillin should be administered as diagnostic therapy. Surgical intervention may be necessary when frequent hemoptysis has no resolution or lung neoplasm cannot be ruled out.


  6229.      Esposito S, Droghetti R, Bosis S, Claut L, Marchisio P, Principi N. Cytokine secretion in children with acute Mycoplasma pneumoniae infection and wheeze. Pediatr Pulmonol. 2002 Aug;34(2):122-7.


The aim of this study was to evaluate cytokine secretion in children with acute Mycoplasma pneumoniae infection and wheeze. We studied 25 patients aged 2-14 years with an acute episode of wheezing (15 with acute M. pneumoniae infection) and 16 healthy controls of similar gender and age (8 with laboratory evidence of asymptomatic acute M. pneumoniae infection). Serum interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-5 concentrations were measured in samples obtained at enrollment, using enzyme-linked immunosorbent assay kits.In the presence of wheezing, IL-5 concentrations were significantly higher in subjects with acute M. pneumoniae infection (33.415 +/- 22.138 pg/mL) than in those without such infection (2.320 +/- 1.846 pg/mL, P < 0.0001). The children with acute M. pneumoniae infection and wheeze had higher IL-5 concentrations (33.415+/-22.138 pg/mL) than those with asymptomatic acute infection and without wheeze (1.740 +/- 2.299 pg/mL, P < 0.0001). No significant between-group differences were observed in terms of IL-2, IFN-gamma, or IL-4 levels, or the prevalence of atopy.Our results show that children with wheezing and acute M. pneumoniae infection have a specific cytokine profile characterized by a significant increase in serum levels of IL-5. This immune response may be important for understanding the pathophysiological mechanisms by which this pathogen contributes to the development of wheeze-related symptoms, and for identifying new treatment strategies. Copyright 2002 Wiley-Liss, Inc.

  6230.      File TM Jr, Hadley JA. Rational use of antibiotics to treat respiratory tract infections. Am J Manag Care. 2002 Aug;8(8):713-27.


OBJECTIVES: To foster the appropriate use of antimicrobial agents for respiratory tract infections and to review factors that should help achieve this objective. STUDY DESIGN: Review of evidence-based guidelines and recommendations for proper antibiotic drug use for respiratory tract infections. RESULTS AND CONCLUSIONS: Antibiotic drug overuse and inappropriate antibiotic drug selection are associated with increased drug resistance among respiratory pathogens (most notably, Streptococcus pneumoniae), possible progression to chronic disease, and increased treatment costs. Awareness of clinical manifestations that help differentiate viral from bacterial infection and the use of guidelines can promote the appropriate management of respiratory tract infections. Community-acquired pneumonia, acute bacterial rhinosinusitis, and selected cases of acute exacerbations of chronic bronchitis (50%) warrant antimicrobial therapy, whereas otitis media with effusion, acute bronchitis, and most rhinosinusitis are viral and do not require antibiotic therapy.

6231.  Guleria R, Thakur M, Sinha S, Sharma SK, Pande JN. Non resolving pneumonia in a young boy. Indian J Chest Dis Allied Sci. 2002 Jul-Sep;44(3):183-5.  No abstract.

6232.  Harmanci A, Harmanci O, Akova M. Hospital-acquired pneumonia: challenges and options for diagnosis and treatment. J Hosp Infect. 2002 Jul;51(3):160-7. Review.


The management of hospital-acquired pneumonia (HAP) presents a major challenge for the clinician. The insensitivity of current diagnostic methods and the increasing prevalence of nosocomial pathogens with multiple antibiotic resistance complicate the issue. Use of mechanical ventilation and broad-spectrum antimicrobials in the intensive care setting predipose patients to acquire HAP more frequently with antimicrobial-resistant pathogens. Controversy exists regarding the patients in which invasive diagnostic testing is indicated; the timing of these procedures is another subject of debate. Proper empirical therapy is fundamental to a favourable outcome, and the selection of inappropriate agents to which pathogens are resistant contributes significantly to morbidity and mortality. In general, there is agreement on the requirement for a thorough knowledge of the local causative organisms and the pathogens' resistance profiles. A wide variety of antimicrobials can be used either as monotherapy or in combinations.


6233.  Jacobs RL. Hypersensitivity pneumonia: UIP/IPF histopathologic presentation. J Allergy Clin Immunol. 2002 Sep;110(3):532-3. No abstract.

6234.  Koval CE, Gigliotti F, Nevins D, Demeter LM. Immune reconstitution syndrome after successful treatment of Pneumocystis carinii pneumonia in a man with human immunodeficiency virus type 1 infection. Clin Infect Dis. 2002 Aug 15;35(4):491-3.


We describe a 34-year-old man with human immunodeficiency virus infection who received successful treatment of minimally symptomatic Pneumocystis carinii pneumonia and who subsequently developed diffuse pulmonary infiltrates and hypoxia 2 weeks after initiation of combination antiretroviral therapy. Initial pathologic evaluation of lung-tissue samples revealed no organisms, but a polymerase chain reaction assay was strongly positive for P. carinii DNA. We hypothesize that this patient's clinical presentation denotes immune reconstitution syndrome in response to residual P. carinii antigen in the lung.

6235.  Loeb M. Community-acquired pneumonia. Am Fam Physician. 2002 Jul 1;66(1):135-7. No abstract.

6236.  McElroy MC, Cain DJ, Tyrrell C, Foster TJ, Haslett C. Increased virulence of a fibronectin-binding protein mutant of Staphylococcus aureus in a rat model of pneumonia. Infect Immun. 2002 Jul;70(7):3865-73.


Fibronectin-binding proteins mediate Staphylococcus aureus internalization into nonphagocytic cells in vitro. We have investigated whether fibronectin-binding proteins are virulence factors in the pathogenesis of pneumonia by using S. aureus strain 8325-4 and isogenic mutants in which fibronectin-binding proteins were either deleted (DU5883) or overexpressed [DU5883(pFnBPA4)]. We first demonstrated that fibronectin-binding proteins mediate S. aureus internalization into alveolar epithelial cells in vitro and that S. aureus internalization into alveolar epithelial cells requires actin rearrangement and protein kinase activity. Second, we established a rat model of S. aureus-induced pneumonia and measured lung injury and bacterial survival at 24 and 96 h postinoculation. S. aureus growth and the extent of lung injury were both increased in rats inoculated with the deletion mutant (DU5883) in comparison with rats inoculated with the wild-type (8325-4) and the fibronectin-binding protein-overexpressing strain DU5883(pFnBPA4) at 24 h postinfection. Morphological evaluation of infected lungs at the light and electron microscopic levels demonstrated that S. aureus was present within neutrophils from both 8325-4- and DU5883-inoculated lungs. Our data suggest that fibronectin-binding protein-mediated internalization into alveolar epithelial cells is not a virulence mechanism in a rat model of pneumonia. Instead, our data suggest that fibronectin-binding proteins decrease the virulence of S. aureus in pneumonia.


6237.  Mehta RM, Niederman MS. Nosocomial pneumonia. Curr Opin Infect Dis. 2002 Aug;15(4):387-94. Review.


PURPOSE OF REVIEW: Despite abundant literature on the management of nosocomial pneumonia, a number of aspects, from diagnosis to the therapy of nosocomial pneumonia, are still controversial. This review focuses on recent advances that can aid in the day-to-day care of these critically ill patients. RECENT FINDINGS: The risk factors for nosocomial pneumonia in specific subsets of trauma, postoperative and burn injury patients have been identified, with emphasis on the type of pneumonia developing in these populations - early or late onset nosocomial pneumonia. Resolution of nosocomial pneumonia, in terms of improvement of clinical parameters such as oxygenation, fever, leukocytosis and bacterial eradication, has been reported, and these data can lead to a better understanding of the natural course of the disease. The importance of initial, accurate empiric therapy in improving mortality in nosocomial pneumonia has been reinforced by multiple studies. Newer techniques to study colonization and the routes of spread of pathogenic organisms in the intensive care unit are adding to our understanding of how pneumonia develops, the role of infection control measures and the types of strategies that are needed for prevention. Oral decontamination is showing promise as a technique to prevent ventilator-associated pneumonia, and noninvasive ventilation has been shown to be useful in various etiologies of respiratory failure, with the beneficial effect of reducing the incidence of ventilator-associated pneumonia and its associated mortality. The implementation of protocolized treatment guidelines and antibiotic rotation policies are emerging as useful tools for reducing the frequency of antibiotic resistance and the impact of nosocomial pneumonia. SUMMARY: There is a better understanding of nosocomial pneumonia risk factors, mechanisms of bacterial colonization, and resolution of illness, with exciting developments in prevention and treatment emerging, and these data can help us achieve more effective management of this complex illness.

6238.  Murray D, Jackson C. A conjugate vaccine for the prevention of pediatric pneumococcal disease. Mil Med. 2002 Aug;167(8):671-7. Review.


The use of the pneumococcal 7-valent conjugate vaccine (PCV7 [Prevnar], Wyeth Lederle Vaccines), and the impact it is likely to have on pneumococcal disease are reviewed. Pneumococcal disease in infants and young children is a major health care burden, and the increase in antibiotic resistance among pneumococci has complicated disease management. The 23-valent polysaccharide pneumococcal vaccines do not protect infants and children younger than 2 years of age. PCV7 is effective in this population and should dramatically reduce the incidence of invasive pneumococcal disease and have an impact on the incidence of infections caused by Streptococcus pneumoniae serotypes present in the vaccine. Research has shown that pneumococcal conjugate vaccines reduce nasopharyngeal carriage of vaccine serotype S. pneumoniae, including antibiotic-resistant strains. Routine immunization is expected to substantially reduce the morbidity and mortality associated with invasive pneumococcal disease in children, and coupled with expected herd immunity and decreased antibiotic selective pressure, it should have a positive impact beyond the immunized population.

6239.  Roblot F, Godet C, Le Moal G, Garo B, Faouzi Souala M, Dary M, De Gentile L, Gandji JA, Guimard Y, Lacroix C, Roblot P, Becq-Giraudon B.  Analysis of Underlying Diseases and Prognosis Factors Associated with Pneumocystis carinii Pneumonia in Immunocompromised HIV-Negative  atients. Eur J Clin Microbiol Infect Dis. 2002 Jul;21(7):523-31.


The aim of this retrospective study was to determine the underlying diseases associated with Pneumocystis carinii pneumonia (PCP) in immunocompromised HIV-negative patients and to identify prognosis factors in this population. One hundred three cases of PCP were diagnosed over a 5-year period. Diagnosis was established on the basis of clinical features and by detection of Pneumocystis carinii cysts in bronchoalveolar lavage fluid. Underlying diseases comprised hematologic malignancies ( n=60; 58%), inflammatory diseases ( n=27; 26%), and solid tumors ( n=18; 17.5%); 9 (8%) patients were solid organ transplant recipients. Seventy-one (69%) patients received cytotoxic drugs, 57 (55%) were treated with long-term corticotherapy, and 15 (14.7%) underwent bone marrow transplantation. Fifty-eight (56%) patients were admitted to the intensive care unit, and 52 (41%) required mechanical ventilation. Thirty-nine (38%) patients died of PCP; data from these patients were compared with those from surviving patients. The following factors were associated with a poor prognosis: high respiratory rate ( P=0.005), high pulse rate ( P=0.0003), elevated C-reactive protein ( P=0.01), elevated serum lactate dehydrogenase level ( P=0.02), and mechanical ventilation (OR, 14.4; 95%CI, 5-50). The results suggest that PCP can occur during the course of many immunosuppressive diseases, particularly various hematologic malignancies. The diagnosis of PCP should be considered more frequently and advocated earlier in immunocompromised HIV-negative patients, since prompt diagnosis may improve the prognosis of these patients.

6240.  Ross JJ, Worthington MG, Gorbach SL. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med. 2002 Jul 4;347(1):65-7; discussion 65-7.  No abstract.

6241.  Scott JA, Obiero J, Hall AJ, Marsh K. Validation of immunoglobulin G enzyme-linked immunosorbent assay for antibodies to pneumococcal surface adhesin A in the diagnosis of pneumococcal pneumonia among adults in Kenya. J Infect Dis. 2002 Jul 15;186(2):220-6.


Epidemiologic studies of pneumococcal pneumonia, including vaccine efficacy trials, are hampered by a lack of sensitive and specific diagnostic tests. Pneumococcal surface adhesin A (PsaA) is a genetically conserved, surface-expressed protein common to all serotypes of Streptococcus pneumoniae and is highly immunogenic. Detection of anti-PsaA immunoglobulin G by recombinant PsaA enzyme-linked immunosorbent assay was evaluated for diagnosis of pneumococcal pneumonia in paired serum samples from 4 adult populations: 47 healthy control subjects, 56 clinic control subjects without pneumococcal disease syndromes, 109 patients with pneumococcal pneumonia, and 93 pneumonia patients with no evidence of pneumococcal etiology. By considering a 2-fold increase in antibody concentration as positive, sensitivity was 0.70, and specificity was 0.98. With a 1.3-fold increase, these were 0.89 and 0.98, respectively. The test's performance was not affected by the patients' human immunodeficiency virus status or by the pneumococcal serotype. The combination of high sensitivity and high specificity makes this an ideal assay for epidemiologic studies of pneumococcal pneumonia.


6242.  Shahin GS, Lerner SA. Rare Presentation of Streptococcus pneumoniae Pneumonia with Bacteremia and Multiple Subcutaneous Abscesses. Eur J Clin Microbiol Infect Dis. 2002 Aug;21(8):611-2.

-Reported here is the case of an apparently immunocompetent patient with Streptococcus pneumoniae pneumonia and bacteremia who presented with abscesses in multiple soft tissue sites. This unusual presentation provided a purulent aspirate for presumptive etiologic diagnosis by a Gram-stained smear.

6243.  Shivananda PG. Unusual case of Flavobacterium meningosepticum pneumonia in an immunocompromised patient. Indian J Path Microbiol. 1999; 42(4): 491-2. No abstract.

6244.  Tan TQ, Mason EO Jr, Wald ER, Barson WJ, Schutze GE, Bradley JS, Givner LB, Yogev R, Kim KS, Kaplan SL. Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae. Pediatrics. 2002 Jul;110(1 Pt 1):1-6.


OBJECTIVE: The frequency of children who are hospitalized with pneumococcal pneumonia complicated by necrosis, empyema/complicated parapneumonic effusion, and lung abscess seems to be increasing. The factors that contribute to this increase are unclear; therefore, the objective of this study was to describe and compare the relative frequency, clinical characteristics, and outcome of hospitalized children with complicated pneumonia with those of children with uncomplicated pneumonia caused by Streptococcus pneumoniae in the era of antibiotic resistance. METHODS: A multicenter, retrospective study of 8 children's hospitals in the United States was undertaken. A total of 368 children who were hospitalized with pneumococcal pneumonia identified from patients enrolled in the US Pediatric Multicenter Pneumococcal Surveillance Study over the period from September 1, 1993, to January 31, 2024 were studied. Demographic and clinical variables, antibiotic susceptibility, pneumococcal serotypes, antimicrobial therapy, and clinical outcome in hospitalized children with complicated versus uncomplicated pneumococcal pneumonia were measured. RESULTS: A total of 368 patients with pneumococcal pneumonia were identified. Of the 368 isolates, 47 (12.8%) were intermediate and 37 (10.1%) were resistant to penicillin; 18 (5%) were intermediate to ceftriaxone, and 9 (2.5%) were resistant to ceftriaxone. A total of 133 patients met the criteria for complicated pneumonia and had a chest tube placed; 56 of these patients subsequently underwent decortication. The proportion of hospitalized patients with complicated pneumococcal pneumonia increased progressively over the study period from 22.6% in 1994 to 53% in 1999. Patients with complicated disease were older (median age: 45 vs 27 months) and significantly more likely to be of white race and have chest pain on presentation compared with patients with uncomplicated disease. Patients who had complicated disease and underwent decortication were more likely to have pleural fluid lactate dehydrogenase levels of >7500 IU/L compared with those patients who had chest tube placement alone. Fifty-three percent of children who were > or =61 months of age and were hospitalized had complicated pneumonia. This group of children accounted overall for 42% of the patients with complicated pneumonia, 48.2% of the patients who subsequently underwent decortication, and 44% of the patients who had received a course of antibiotics before diagnosis. Pneumococcal serotypes 1, 6, 14, and 19 were the most prevalent serotypes causing disease, with serotype 1 causing 24.4% of the complicated cases versus 3.6% of the uncomplicated cases. Ninety-eight percent of the patients in both groups recovered from their pneumonia. Antibiotic resistance was not found to be more prevalent in those patients with complicated disease. CONCLUSIONS: The relative frequency of complicated disease in hospitalized children with pneumococcal pneumonia is increasing. Patients with complicated pneumococcal disease were older and significantly more likely to be of white race compared with those patients with uncomplicated disease. Pneumococcal serotype 1 caused significantly more disease in patients with complicated versus uncomplicated pneumonia. Patients with complicated disease were not more likely to be infected with an antibiotic-resistant isolate.


6245.  Timmer SJ, Amundson DE, Malone JD. Hypersensitivity pneumonitis following anthrax vaccination. Chest. 2002 Aug;122(2):741-5.


OBJECTIVE: To find a parameter that would discriminate between the patients with idiopathic interstitial pneumonia who survived to undergo transplantation and those who died while waiting to undergo transplantation. METHODS: A retrospective review was performed of all lung transplant referrals for idiopathic interstitial pneumonia that were listed with United Network for Organ Sharing at the University of California San Diego from January 1990 to February 1999. Of the 331 patients who were listed, 48 met the eligibility criteria. Patient demographics, radiographic studies, pathology reports, and the results of resting and exercise cardiopulmonary function tests were recorded from each patient's chart. Patients were divided into the following two groups: those patients who survived until transplantation and those still waiting were classified as "alive"; and those patients who died before undergoing transplantation were classified as "deceased." RESULTS: Forty-three of 48 patients had a pathologic diagnosis. The cohort included 25 patients with usual interstitial pneumonitis, 3 patients with nonspecific interstitial pneumonitis, 1 patient with desquamative interstitial pneumonitis, and 14 patients with interstitial lung disease of unknown etiology. The only significant difference between the two groups was resting PaO(2) (p = 0.035). A stepwise multivariate analysis demonstrated that PaO(2) and FEV(1)/FVC ratio were significantly associated with survival (hazards ratio, 1.06; confidence interval, 0.99 to 1.13; p = 0.019). CONCLUSIONS: A survival analysis using PaO(2) and FEV(1)/FVC ratio values proved to be statistically significant, but a prospective trial is needed to determine the clinical relevance of these parameters for predicting survival in patients with idiopathic interstitial pneumonia.


6247.  Alangaden GJ, Wahiduzzaman M, Chandrasekar PH. Aspergillosis: The most common community-acquired pneumonia with gram-negative Bacilli as copathogens in stem cell transplant recipients with graft-versus-host disease. Clin Infect Dis. 2002 Sep 15;35(6):659-64.


We retrospectively reviewed all cases of pneumonia that required hospitalization among allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) during the period of January 1996 through July 1999. Twelve patients were identified among 88 allogeneic HSCT recipients. All had chronic GVHD and were receiving corticosteroid therapy. Ten of the 12 patients had pulmonary aspergillosis (PA). For 6 of these 10 patients, a gram-negative bacterial pathogen was concurrently isolated from respiratory specimens. At least one-half of the patients with PA had an initial presentation suggestive of bacterial pneumonia; PA was only suspected on the basis of chest CT findings. Aspergillosis is the most common cause of community-acquired pneumonia among allogeneic HSCT recipients with GVHD. CT must be used to exclude an underlying fungal cause in patients who present with a gram-negative pneumonia.


6248.  Cook DJ, Meade MO, Hand LE, McMullin JP. Toward understanding evidence uptake: semirecumbency for pneumonia prevention. Crit Care Med. 2002 Jul;30(7):1472-7.


OBJECTIVE: Randomized trials show that the semirecumbent position compared with the supine position is associated with less gastroesophageal aspiration and pneumonia in patients receiving mechanical ventilation. However, semirecumbency is inconsistently used in practice. The objective of this study was to understand the perspectives of intensive care unit clinicians regarding the determinants and consequences of semirecumbency. DESIGN: Qualitative study using semistructured interviews and focus groups. SETTING: Three university-affiliated intensive care units. PARTICIPANTS: A total of 93 intensive care unit clinicians, including bedside nurses, respiratory therapists, physiotherapists, nutritionists, residents, fellows, and intensivists. METHODS: We elicited perceptions about benefits and harms of semirecumbency, factors promoting and deterring use, and health systems changes to encourage semirecumbency. Interview and focus group notes were analyzed inductively to identify emerging themes. Validation methods involved triangulation by multidisciplinary analysis of several data sources collected through multiple methods and member checking. MEASUREMENTS AND MAIN RESULTS: Intensivists and nutritionists were familiar with semirecumbency as a potential pneumonia prevention strategy, whereas other clinicians were not. When made aware of the evidence, all participants endorsed semirecumbency. Nurses perceived that the main determinant of semirecumbency was physicians' orders, whereas intensivists perceived that the main determinant was nursing preference. Participants identified barriers to semirecumbency related to useful alternative positions (e.g., lateral position), contraindications (e.g., hemodynamic instability), risk of harm (e.g., decubitus ulcers), safety (e.g., sliding out of the bed), and resources (e.g., insufficient beds facilitating semirecumbency). Education, guidelines, reminders, audit and feedback, charting, and quality improvement initiatives were advocated to promote semirecumbency. CONCLUSIONS: Under-utilization of semirecumbency for pneumonia prevention is influenced by insufficient awareness of its benefit, real and perceived deterrents, poor agreement about implementation

responsibility, and lack of enabling and reinforcing strategies. Cognitive,

behavioral, and administrative approaches to enhancing evidence uptake may be needed in the complex, dynamic intensive care unit setting.

6249.  de Lassence A, Alberti C, Azoulay E, Le Miere E, Cheval C, Vincent F, Cohen Y, Garrouste-Orgeas M, Adrie C, Troche G, Timsit JF. Impact of unplanned extubation and reintubation after weaning on nosocomial pneumonia risk in the intensive care unit: a prospective multicenter study. Anesthesiology. 2002 Jul;97(1):148-56.


BACKGROUND: The authors prospectively evaluated the occurrence and outcomes of unplanned extubations (self-extubation and accidental extubation) and - reintubation after weaning, and examined the hypothesis that these events may differ regarding their influence on the risk of nosocomial pneumonia. METHODS: Data were taken from a prospective, 2-yr database including 750 mechanically ventilated patients from six intensive care units. RESULTS: One hundred five patients (14%) experienced at least one episode of these 3 events; 51 self-extubations occurred in 38 patients, 24 accidental extubations in 22 patients, and 56 reintubations after weaning in 45 patients. The incidence density of these 3 events was 16.4 per 1,000 mechanical ventilation days. Reintubation within 48 h was needed consistently after accidental extubation but was unnecessary in 37% of self-extubated patients. Unplanned extubation and reintubation after weaning were associated with longer total mechanical ventilation (17 vs. 6 days; P < 0.0001), intensive care unit stay (22 vs. 9 days; P < 0.0001), and hospital stay (34 vs. 18 days; P < 0.0001) than in control group, but did not influence intensive care unit or hospital mortality. The incidence of nosocomial pneumonia was significantly higher in patients with unplanned extubation or reintubation after weaning (27.6% vs. 13.8%; P = 0.002). In a Cox model adjusting on severity at admission, unplanned extubation and reintubation after weaning increased the risk of nosocomial pneumonia (relative risk, 1.80; 95% confidence interval, 1.15-2.80; P = 0.009). This risk increase was entirely ascribable to accidental extubation (relative risk, 5.3; 95% confidence interval, 2.8-9.9; P < 0.001). CONCLUSION: Accidental extubation but not self-extubation or reintubation after weaning increased the risk of nosocomial pneumonia. These 3 events may deserve evaluation as an indicator for quality-of-care studies.


6250.  de Monbrison F, Picot S. Introducing antisense oligonucleotides into Pneumocystis carinii. J Microbiol Methods. 2002 Jul;50(2):211-3.


To improve the knowledge on Pneumocystis carinii growth, a homologous P. carinii transformation system would provide a tool to promote replication of this fungus. Antisense oligonucleotides have been successfully introduced by electroporation or direct uptake in order to downregulate the prohibitin negative function on cell cycle.

6251.  Lin XQ, O'Reilly KL, Storz J. Antibody Responses of Cattle with Respiratory Coronavirus Infections during Pathogenesis of Shipping Fever Pneumonia Are Lower with Antigens of Enteric Strains than with Those of a Respiratory Strain. Clin Diagn Lab Immunol. 2002 Sep;9(5):1010-3.


The serum antibody responses of cattle with respiratory coronavirus infections during the pathogenesis of shipping fever pneumonia were analyzed with different bovine coronavirus antigens, including those from a wild-type respiratory bovine coronavirus (RBCV) strain (97TXSF-Lu 15-2) directly isolated from lung tissue from a fatally infected bovine, a wild-type enteropathogenic bovine coronavirus (EBCV) strain (Ly 138-3), and the highly cell culture-adapted, enteric prototype strain (EBCV L9-81). Infectivity-neutralizing (IN) and hemagglutinin-inhibiting (HAI) activities were tested. Sequential serum samples, collected during the onset of the respiratory coronavirus infection and at weekly intervals for 5 weeks thereafter, had significantly higher IN and HAI titers for antigens of RBCV strain 97TXSF-Lu15-2 than for the wild-type and the highly cell culture-adapted EBCV strains, with P values ranging from <0.0001 to 0.0483. The IN and HAI antibody responses against the two EBCV strains did not differ significantly, but the lowest titers were detected with EBCV strain L9-81.


6252.  McGarry H, McLelland J. Pneumocystis carinii pneumonia in a patient on immunosuppressive drugs for pyoderma gangrenosum. Br J Dermatol. 2002 Jul;147(1):192-3. No abstract.

6253.  Sebert ME, Palmer LM, Rosenberg M, Weiser JN. Microarray-based identification of htrA, a Streptococcus pneumoniae gene that is regulated by the CiaRH two-component system and contributes to nasopharyngeal colonization. Infect Immun. 2002 Aug;70(8):4059-67.


Nasopharyngeal carriage is the reservoir from which most disease with Streptococcus pneumoniae arises. Survival as a commensal in this environment is likely to require a set of adaptations distinct from those needed to cause disease, some of which may be mediated by two-component signal transduction systems (TCSTS). We examined the contributions of nine pneumococcal TCSTS to the process of nasopharyngeal colonization by using an infant rat model. Whereas deletions in all but one of these systems have been associated previously with a high degree of attenuation in a murine model of pneumonia, only the CiaRH system was necessary for efficient carriage. Transcriptional analysis by using microarray hybridization identified a locus consisting of two adjacent genes, htrA and spoJ, that was specifically and strongly downregulated in a DeltaciaRH-null mutant. A S. pneumoniae strain lacking the htrA gene encoding a putative serine protease, but not one lacking spoJ, showed decreased fitness in a competitive model of colonization, a finding consistent with this gene mediating a portion of the carriage deficit observed with the DeltaciaRH strain.


6254.  Yokoyama T, Sakamoto T, Shida N, Shimada T, Kaku N, Aizawa H, Oizumi K.  Bacteremic and leukopenic pneumococcal pneumonia: successful treatment with antibiotics, pulse steroid, and continuous hemodiafiltration. J Infect Chemother. 2002 Sep;8(3):247-51.


We describe a case of bacteremic, leukopenic pneumococcal pneumonia with respiratory failure, accompanied by diabetic ketoacidosis and hypothermia. Pulmonary leukostasis may play a role in the pathogenesis of the acute respiratory distress syndrome (ARDS) in pneumoococcal pneumonia. The patien recovered with mechanical ventilation, intravenous antibiotics, pulse-steroid therapy, and continuous hemodiafiltration (CHDF). In particular, administration of steroid and the use of CHDF may improve the status of pulmonary leukostasis in leukopenic pneumococcal infection.


6255.  Appleyard GD, Furesz SE, Wilkie BN. Blood lymphocyte subsets in pigs vaccinated and challenged with Actinobacillus pleuropneumoniae. Vet Immunol Immunopathol. 2002 Jul;86(3-4):221-8.


Actinobacillus pleuropneumoniae bacterins do not induce protection in pigs while infection with low doses of the CM5 strain of A. pleuropneumoniae given by aerosol induces complete protection. To evaluate possible correlates of protection in blood lymphocyte subset phenotypes, pigs were treated with a commercial bacterin given intramuscularly, low dose (10(5)cfu/ml) aerosol infection with CM5 or control treatments of the bacterin adjuvant or phosphate buffered saline. All pigs were challenged with a high dose (10(7)cfu/ml) of A. pleuropneumoniae. Lymphocytes and sera were collected prior to and following primary and secondary immunizations and challenge, for evaluation of B- and T-cell markers and antibody to four A. pleuropneumoniae antigens. IgM(micro)+ B-cells were increased following primary exposure to antigen in the bacterin-vaccinated group only. An increase in CD4+ cells in the LD aerosol-infected group was apparent following secondary exposure to antigen. These early changes suggest little difference in lymphocyte populations between treatment groups, however, greater differences were observed following high-dose challenge; CD4+ lymphocytes were increased significantly in both bacterin and LD-challenged groups (p<0.05) while CD8+ cells decreased in the LD-group at this time period. Consequently, there were significant differences (p<0.05) in the CD4:CD8 ratio after high-dose challenge compared to earlier time points and control groups. Variation in cellular expression of SLA-DR and DQ was observed but trends correlating to treatment group were not evident. Complete protection or lack of protection associated with LD challenge or immunisation resulted in significant differences in B-cell frequencies and CD4:CD8 ratio phenotypes in pigs, but only changes in CD4:CD8 ratios appeared relevant to protection.

6256.  Di Guilmi AM, Dessen A. New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae. EMBO Rep. 2002 Aug;3(8):728-34.


Streptococcus pneumoniae causes more than one million deaths every year, mostly of young children in developing countries, due to pneumonia, bacteremia and meningitis. The emergence and dissemination of drug-resistant pneumococcal strains, coupled to changing patterns of virulence and the inadequacy of available vaccines, calls for an aggressive search for novel targets for antibiotic and vaccine development. Microbial genomics techniques allow genetic and biochemical tools to be employed to tackle discovery, design and development of new anti-infective agents based on the identification of hundreds of new targets. In this review, novel approaches employed to identify potential antibiotic and vaccine targets in S. pneumoniae are highlighted. Recently identified virulence factors, as well as molecules essential for bacterial viability, cell wall integrity and infectivity, are discussed.

6257.  Jacobson RM, Poland GA. The pneumococcal conjugate vaccine. Minerva Pediatr. 2002 Aug;54(4):295-303.


Streptococcus pneumoniae is the most frequent cause of otitis media, sinusitis, and pneumonia in children. It is also one of the most common causes of invasive bacterial infections in children including bacteremia and meningitis. One of the current issues regarding S. pneumoniae is the emergence of pneumococcal strains resistant to penicillin and other antibiotics. Children less than two years of age suffer an increased incidence of invasive pneumococcal disease but fail to respond to the 23-valent polysaccharide vaccine because of the immaturity of the T-cell independent immune function. Covalently conjugating the polysaccharide antigen to a carrier protein improves the immune response by permitting the host to utilize a T-cell dependent immune response that is adequately mature in children less than two years of age. Immunogenicity studies of the currently licensed heptavalent conjugated polysaccharide vaccine, (Prevnar, marketed by Wyeth Lederle Vaccines) demonstrated that infants vaccinated with three doses 2 months apart at 2, 4, and 6 months of age successfully developed antibodies to all 7 serotypes; booster doses at 12-15 months demonstrated an amnestic response for each serotype. Immunogenicity studies have similarly demonstrated successful responses in children with sickle cell disease and human immunodeficiency virus infection. An efficacy trial involving nearly 38,000 subjects demonstrated the vaccine's effectiveness in healthy children against invasive pneumococcal disease as well as against pneumonia and otitis media. Currently the US Advisory Committee on Immunization Practices (ACIP) recommends that all infants and children under 24 months of age receive the vaccine. The ACIP recommends that infants receive the vaccine routinely at 2, 4 and 6 months with a fourth dose at 12 to 15 months of age. Infants may receive the first dose as early as 6 weeks of age. The vaccine is also indicated for children 24 to 59 months of age who are at high risk for pneumococcal infection. Adverse events include local reactions in the first two days following vaccination such as approximately 10% reporting erythema, 10% induration, and 20% tenderness. Fever of 38 degrees C or higher occurred in 15% to 25% of children in the first two days following vaccination. Follow-up studies should address important questions regarding the use of pneumococcal conjugate vaccine and other age groups.

6258.  Overturf GD. Pneumococcal vaccination of children. Semin Pediatr Infect Dis. 2002 Jul;13(3):155-64.


Streptococcus pneumoniae is the most frequent cause of invasive bacterial infection in children younger than 2 years of age, reaching a peak incidence at 6 to 12 months of age. Pneumococci also cause many cases of pneumonia, sinusitis, and otitis media. Incidence rates of invasive infection in children with sickle cell disease, acquired or congenital splenectomy, or human immunodeficiency virus infection are 20- to 100-fold higher than are those of healthy children during the first 5 years of life. Other healthy children, such as those of American Indian, Native Alaskan, or African American descent, also have high rates of invasive infection, and those children enrolled in out-of-home care may have modestly increased risks. Pneumococcal polysaccharide polyvalent vaccines have been available for more than 2 decades but are limited in their usefulness for children because of their inability to induce protective antibody responses in children younger than 2 years of age and lack of immunologic memory. In contrast, pneumococcal protein conjugate vaccines induce presumptive protective responses in infants younger than 6 months, and immunologic memory further enhances responses after booster doses are given. Currently, a single heptavalent pneumococcal protein conjugate vaccine is licensed for use in the United States and is recommended for routine administration to all children, beginning at 2 months of age. It also is recommended for children between 24 and 59 months of age who are at high risk of acquiring invasive disease.

6259.  Wuorimaa T, Kayhty H. Current state of pneumococcal vaccines. Scand J Immunol. 2002 Aug;56(2):111-29. Review.


Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and acute otitis media in children and adults worldwide. According to World Health Organization estimates, at least 1 million children under 5 years of age die each year from pneumococcal pneumonia. The emergence of resistant strains necessitates the development of an effective vaccine with a large serotype coverage. The 11 most common serotypes cause 72-83% of all serious pneumococcal diseases worldwide. Currently marketed 23-valent pneumococcal polysaccharide vaccine provides large serotype coverage and offers a less expensive option. However, it is efficacious only in adults but not in infants. Conjugate vaccines offer a solution by generating immunological memory already at early age. A recently licensed 7-valent conjugate vaccine is immunogenic and efficacious in infants. Its serotype coverage might be sufficient in Europe and North America, but not in Africa, Asia and Oceania. A need exists to develop pneumococcal vaccines with lower cost and larger serotype coverage. Several 11-valent pneumococcal conjugate vaccines are being evaluated in phase I-III trials. This study reviews the current state of pneumococcal problem and pneumococcal vaccines in clinical use.



6260.  Garau J. Treatment of drug-resistant pneumococcal pneumonia. Lancet Infect Dis. 2002 Jul;2(7):404-15. Review.


The increasing prevalence of resistance to penicillin and other drugs among pneumococci has considerably complicated the empirical treatment of community-acquired pneumonia. Penicillin resistance has become widespread and is a worldwide occurrence. Resistance to other classes of antibiotics traditionally used as alternatives in the treatment of pneumococcal infections has also increased markedly during recent years. In some areas of the USA, Europe, and east Asia a prevalence of macrolide resistance as high as 35% or more has been reported recently. From the clinical standpoint, a growing number of failures following the use of these agents has been described. Resistance to fluoroquinolones remains low but several failures have been reported in different parts of the world. Pharmacokinetic/pharmacodynamic parameters have become essential at the time of making a rational choice and calculation of dosage. Penicillin G remains the mainstay of therapy for the treatment of penicillin-susceptible pneumococcal pneumonia. Penicillin-resistant pneumococcal pneumonia (minimum inhibitory concentration <4 microg/mL) can be safely treated with adequate betalactams at the right dosage. The new fluoroquinolones are very

active and effective in pneumococcal pneumonia. Caution should be exercised in the widespread prescription of these drugs if we are to limit the rate of resistance to these agents.


6261.  Gould IM. BTS guidelines on CAP. Community acquired pneumonia. Thorax. 2002 Jul;57(7):657. No abstract.

6262.  Hutt E, Kramer AM. Evidence-based guidelines for management of nursing home-acquired pneumonia. J Fam Pract. 2002 Aug;51(8):709-16.


We convened a multidisciplinary, multispecialty panel to develop comprehensive evidence and consensus-based guidelines for managing nursing home-acquired pneumonia. The panel began with explicit criteria for process of care quality measures, performed a comprehensive review of the English-language literature, evaluated the quality of the evidence, and drafted a set of proposed guidelines. The panel reviewed the draft, an annotated bibliography, and data from a study of 30-day survival from nursing home-acquired pneumonia, and then participated in an all-day meeting in January 2001. Using a modified Delphi process, the panel refined the guidelines and developed a care pathway. The guidelines recommend a comprehensive approach, including immunization of staff and residents, and communication between nursing staff and the attending physician within 2 hours of symptom onset. Probable pneumonia was defined. An algorithm was delineated for assessing the patientamprsquos wishes for hospitalization and aggressive care, and deciding on hospitalization based on the severity of the illness as well as the capacity of the nursing home to provide acute care. The timing and extent of evaluation in a nursing home relative to the rapid initiation of antibiotics should depend on whether the patient has any unstable vital signs. An antibiotic covering Streptococcus pneumoniae, Haemophilus influenzae, common gram-negative rods, and Staphylococcus aureus should be given for 10 to 14 days, orally if the patient is able to take medications by mouth.


  6263.      Rello J, Lorente C, Bodi M, Diaz E, Ricart M, Kollef MH. Why do physicians not follow evidence-based guidelines for preventing ventilator-associated pneumonia?: a survey based on the opinions of an international panel of intensivists. Chest. 2002 Aug;122(2):656-61.


OBJECTIVE: Adherence to clinical practice guidelines is highly variable. Our objective was to review barriers to physicians' adherence to evidence-based guidelines (EBGs) for preventing ventilator-associated pneumonia (VAP). METHODS: A questionnaire was administered to 110 opinion leaders on VAP from 22 countries to indicate whether 33 pharmacologic and nonpharmacologic practices that had been listed in a recent publication had been implemented in their ICUs. If these prevention strategies were not used, the respondents were asked to indicate one of seven reasons for nonadherence, with the objective of identifying barriers to adherence to EBGs. RESULTS: The overall nonadherence rate was 37.0%. The nonadherence rate was 25.2% for strategies recommended for clinical use, compared with 45.6% for strategies with less effectiveness (odds ratio [OR], 1.80). Pharmacologic strategies had a higher degree of nonadherence than nonpharmacologic strategies (OR, 2.92). Nonadherence to recommendations graded A, B, C, D, and U based on an objective assessment of the consistency of the supporting evidence was 41.3%, 35.7%, 16.0%, 45.7%, and 20.8%, respectively. The most common reasons for nonadherence were the following: disagreement with interpretation of clinical trials (35%); unavailability of resources (31.3%); and costs (16.9%). CONCLUSION: We conclude that nonadherence to EBGs for preventing VAP was common and largely uninfluenced by the degree of evidence. A rational approach toward improving VAP guideline adherence should take into account the heterogeneous factors that influence physician adherence to them.

 April 2003 


6832.      Abiad H. Does the use of fluoroquinolones for the empiric treatment of pneumonia delay initiation of treatment of tuberculosis? Clin Infect Dis. 2002 Dec 15;35(12):1572; author reply 1572-3.No abstract.

6833.      Asnis DS, Cherian S, Sun T, Shrestha S, Santucci T Jr. Pulmonary tuberculosis presenting as community-acquired pneumonia. Clin Infect Dis. 2002 Dec 15;35(12):1574-5.No abstract

6834.      Balter M.Just the berries. Management of community-acquired pneumonia. Evidence-based update.Can Fam Physician. 2002 Nov;48:1773-5. No abstract.

6835.      Benin AL, Benson RF, Besser RE. Trends in legionnaires disease, 1980-1998: declining mortality and new patterns of diagnosis. Clin Infect Dis. 2002 Nov 1;35(9):1039-46.

New diagnostic tests and empirical therapy for pneumonia may have important ramifications for the identification, treatment, and control of legionnaires disease (LD). To determine trends in the epidemiology of LD, we analyzed data for 1980-1998 from the passive surveillance system of the Centers for Disease Control and Prevention. During this time period, there were 6757 confirmed cases of LD (median annual number, 360 cases/year). Diagnosis by culture and by direct fluorescent antibody and serologic testing decreased significantly; diagnosis by urine antigen testing increased from 0% to 69%. The frequency of isolates other than Legionella pneumophila serogroup 1 (LP1) decreased from 38% to 4% (P=.003). The case-fatality rate decreased significantly, from 34% to 12% (P<.001) for all cases, from 46% to 14% (P<.0001) for nosocomial cases, and from 26% to 10% (P=.05) for community-acquired cases. LD-related mortality has decreased dramatically. The decrease in culture-based diagnosis limits the recognition of

non-LP1 disease and impairs outbreak investigation, because fewer Legionella isolates are provided for further examination.

6836.      Daga M K , Arora N, Gupta D, Krishna Prakash S. Community acquired pnumonia - a hospital based study. Curr med Trends 2001 ,5(2),905-10.(ISA 013329,Vol 38 No13 1 July 2023)

6837.      Dua K, Bardan E, Ren J, Sui Z, Shaker R. Effect of chronic and acute cigarette smoking on the pharyngoglottal closure reflex. Gut. 2002 Dec;51(6):771-5.

BACKGROUND: Injection of water into the pharynx at a threshold volume induces vocal cord adduction--the pharyngoglottal closure reflex (PGCR). This reflex together with other supraoesophageal reflexes may be helpful in preventing aspiration. Cigarette smoking has an adverse affect on the pharyngo-upper oesophageal sphincter contractile reflex and reflexive pharyngeal swallow. The effect of smoking on PGCR has not been studied previously. AIMS: To elucidate the effect of chronic and acute cigarette smoking on PGCR. SUBJECTS: We studied 10 chronic smokers and 10 non-smokers before and after real/simulated smoking, respectively. METHODS: Using concurrent recordings, glottal function was monitored by video endoscopy, swallowing by electromyography, and PGCR was triggered by rapid and slow pharyngeal water injections. RESULTS: The threshold volume to trigger PGCR during rapid injection was significantly higher in chronic smokers (non-smoker 0.20 (SEM 0.02) ml, smoker 0.36 (0.02) ml; p<0.001). In six of 10 smokers, acute smoking abolished this reflex during slow water injection. CONCLUSIONS: Smoking adversely affects stimulation of PGCR. This finding may have implications in the development of reflux related respiratory complications in smokers.

6838.  Hoadley D, Mera R, Bosfield E, Schwarzberg F, Levin J, Farrell B. Interview-based conclusions about rural versus urban HIV care: questions about the questions.J Acquir Immune Defic Syndr. 2002 Nov 1;31(3):365-7. No Abstract

6839.  Kim EA, Lee KS, Primack SL, Yoon HK, Byun HS, Kim TS, Suh GY, Kwon OJ, Han J. Viral pneumonias in adults: radiologic and pathologic findings. Radiographics. 2002 Oct;22 Spec No:S137-49.

The combination of the two methods improved the result to 172 of 178 patients (96.6%). The sensitivities were 94.6%, 88.3% and 97.2%, respectively, for each result. In the benign group, 71.1% (64/90), 70.1% (47/67) and 74.2% (49/66) of cases received specific or nonspecific diagnoses by FNA, core biopsy and their combination, respectively. The rates of specific diagnoses were 20.1%, 21.0% and 31.8%, respectively. CONCLUSION: The combination of FNA and core biopsy markedly improved the diagnostic yields in the malignant group and, to a lesser degree, also in the benign group.

6840.  Lizewski SE, Lundberg DS, Schurr MJ. The transcriptional regulator AlgR is essential for Pseudomonas aeruginosa pathogenesis.Infect Immun  2002 Nov;70(11):6083-93

Chronic Pseudomonas aeruginosa lung infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. One P. aeruginosa virulence factor unique to CF isolates is overproduction of alginate, phenotypically termed mucoidy. Mucoidy is the result of increased transcription from the algD gene and is activated by the transcriptional regulator AlgR. Mutations in algR result in a nonmucoid phenotype and loss of twitching motility. Additionally, AlgR controls transcription of algC, encoding a dual-function enzyme necessary for both lipopolysaccharide (LPS) and alginate production. Therefore, to determine the effect of algR on P. aeruginosa virulence, an algR mutant was examined for sensitivity to reactive oxygen intermediates, killing by phagocytes, systemic virulence, and the ability to maintain a murine lung infection. We found that P. aeruginosa PAO700 (algR::Gm(r)) was less lethal than PAO1, as tested in an acute septicemia infection mouse model, and was cleared more efficiently in a mouse pneumonia model. Additionally, the algR mutant (PAO700) was more sensitive to hypochlorite. However, PAO700 was more resistant to hydrogen peroxide and killed less readily in an acellular myeloperoxidase assay than PAO1. There was little difference in killing between PAO1 and PAO700 with macrophage-like J774 cells and human polymorhonuclear leukocytes. Two-dimensional gel analysis of P. aeruginosa algR mutant and wild-type protein extracts revealed 47 differentially regulated proteins, suggesting that AlgR plays both a positive role and a negative role in gene expression. Together, these results imply that AlgR is necessary for virulence and regulates genes in addition to the genes associated with alginate and LPS production and pilus function.


6841.  Maltezou HC, Raoult D. Q fever in children. Lancet Infect Dis. 2002 Nov;2(11):686-91.

Q fever is a zoonosis caused by Coxiella burnetii. Farm animals and pets are the main reservoirs of infection, and transmission to human beings is mainly accomplished through inhalation of contaminated aerosols. This illness is associated with a wide clinical spectrum, from asymptomatic or mildly symptomatic seroconversion to fatal disease. Q fever in children has been rarely reported. We reviewed published work on this topic. Seroepidemiological studies show that children are frequently exposed to C burnetii. However, children are less frequently symptomatic than adults following infection, and may have milder diseases. Using the standard diagnostic criteria, we identified 46 published paediatric cases only. Self-limited febrile illness and pneumonia were the most common manifestations of acute Q fever. Chronic disease manifested as endocarditis and osteomyelitis. A history of exposure to possible sources of infection with C burnetii in a child with a compatible infectious syndrome should prompt testing for Q fever. Studies are required to determine the spectrum of morbidity associated with Q fever during childhood.

6842.  Miller J, Colasurdo GN, Khan AM, Jajoo C, Patel TJ, Fan LL, Elidemir O. Immunocytochemical detection of milk proteins in tracheal aspirates of ventilated infants: a pilot study. Pediatr Pulmonol. 2002 Nov;34(5):369-74.

In this study, we evaluated immunocytochemical staining for milk proteins (alpha-lactalbumin and beta-lactoglobulin) in tracheal aspirates of mechanically ventilated infants, and assessed whether this staining technique supported a clinical diagnosis of aspiration in infants receiving orogastric feedings. All newborns requiring mechanical ventilation in the neonatal intensive care unit of a major tertiary care hospital were potential subjects for this study. Tracheal aspirates were obtained prior to the introduction of enteral feeding and at various time points thereafter in newborns requiring mechanical ventilation. Cells were obtained and processed for immunocytochemical staining of alpha-lactalbumin and beta-lactoglobulin. In total, 88 specimens recovered from 34 infants were adequate for staining. Alveolar macrophages recovered from most of the infants who were never fed (true negative controls) did not display immunoreactivity for milk proteins: 4/34 or 12% of infants' aspirates demonstrated presence of milk proteins before enteral feeding was commenced. Tracheal aspirates obtained from 12 infants after introduction of enteral feedings appeared to support clinical and radiological findings suggestive of aspiration events, with positive immunostaining on several occasions. These

observations support our work in a murine model and demonstrate that immunocytochemical staining of tracheal aspirates for milk proteins may enhance the ability to diagnose pulmonary aspiration. Further studies are needed to define the clinical significance of our findings and the effects of single and repeated aspiration events on respiratory status. Copyright 2002 Wiley-Liss, Inc.

6843.  Rajalakshmi B; Kanungo R; Srinivasan S; Badrinath S Pneumolysin in Urine: a rapid antigen detection method to diagnose pneumococcal pneumonia in children Indian Journal of Medical Microbiology. 2002 Oct; 20(4): 183-6 .

ABSTRACT: Purpose: Etiological diagnosis of pneumococcal pneumonia is difficult in small children in whom blood culture cannot be done or who have already been started on antibiotics. A simple technique which can be applied at the bedside or in the outpatient department may help in obviating this problem. Detection of pneumolysin, a product of invasive pneumococci is being exploited as a diagnostic tool. Methods: An attempt was made to detect this protein in urine of seventy children, Clinically suspected and radiologically diagnosed cases of pneumonia. Seventy age and sex matched controls were included in the study. Purified pneumolysin was prepared from clinical isolates of invasive pneumococcal infections. This was used to raise polyclonal antisera in rabbits. The antisera was used to sensitise Cowan 1 Staphylococcus aureus (CoA). A slide agglutination was performed with 25 MIUL urine and equal quantity of the reagent. Results: Results were compared with CoA reagent sensitised with antisera raised against a genetically derived pneumolysoid and capsular polysaccharide for antigen detection in the urine. Pneumolysin could be detected in 42.9 percent(30/70) urine samples from cases with pneumonia by the genetically derived antigen and in 37.1 percent samples by the in house prepared antigen, in contrast to 2.1 percent in healthy controls and 4.2 percent in children with infections other than pneumonia. The results was statistically significant. Detection of pneumolysin was slightly better that detection of capsular polysaccharide antigen in urine although the result was not statistically significant. Blood culture proved to be positive in only 29.5 percent cases. Conclusions: Pneumolysin detection in urine showed promising results and was found to be simple and rapid. It will help in quickening the diagnosis of pneumococcal pneumonia.

6844.  Subha A; Ananthan S. Extended spectrum beta lactamase (ESBL) mediated resistance to third generation cephalosporins among Klebsiella pneumoniae in Chennai Indian Journal of Medical Microbiology. 2002 Apr.; 20(2): 92-5 No abstract



6845.  Peckham D, Elliott MW. Pulmonary infiltrates in the immunocompromised: diagnosis and management. Thorax. 2002 Oct;57 Suppl 2:II3-II7. No abstract.

6846.  Ryu JH, Olson EJ, Midthun DE, Swensen SJ. Diagnostic approach to the patient with diffuse lung disease. Mayo Clin Proc. 2002 Nov;77(11):1221-7; quiz 1227.

Detecting diffuse lung infiltrates on chest radiography is a common clinical problem. Many diverse pathological processes can cause diffuse lung disease. The presentation of these diseases can vary from acute to chronic and includes a side array of radiological patterns that are optimally evaluated on high-resolution computed tomography of the chest. In diagnosing diffuse lung disease, it is helpful to focus on a few pivotal parameters to narrow the broad differential diagnosis. We describe the diagnostic approach to a patient with diffuse lung disease usingthe following key parameters: tempo of the pathological process, characteristics of the radiological pattern, and clinical context.

6847.      Tanen DA, Trocinski DR. The use of pulse oximetry to exclude pneumonia in children. Am J Emerg Med. 2002 Oct;20(6):521-3.

The objective of this study was to determine whether pulse oximetry alone or in conjunction with the clinical examination is predictive of pneumonia in children who present to the emergency department with respiratory complaints. A retrospective comparison of children with radiographic pneumonia with children with respiratory complaints and negative chest radiography was used. The study took place in an emergency department of a large academic, tertiary care hospital. All children less than 24 months of age who presented with a respiratory complaint and underwent chest radiography during a 1-year period were included. Charts of children with radiographic pneumonia were compared with charts of children without pneumonia, retrospectively. Data abstracted onto data collection forms included: pulse oximetry measurement, vital signs, general appearance, lung examination, and final radiology interpretation of chest radiographs. Pneumonia was defined as a chest radiograph showing any opacity consistent with pneumonia as read by a board-prepared or -certified radiologist. A total of 803 children qualified for the study. Radiograph interpretations were available for 762, and 10.5% were found to have radiographic pneumonia. The median pulse oximetry reading of children with radiographic pneumonia was 97% (interquartile range 95th-98th percentile) compared with 98% (interquartile range 96th-99th percentile) in the control group. Forty-five percent (35 of 78) of the children with radiographic pneumonia showed oxygen saturations of 98% or higher with greater than 10% (8 of 78) displaying oxygen saturations of 100%. By using logistic regression, pulse oximetry was not found to be a statistically significant predictive variable for radiographic pneumonia. Pulse oximetry could not be used to rule out the presence of radiographic pneumonia in children less than 2 years of age who presented with respiratory complaints.


6848.      Garrison MW, Olds MJ. New potential in pneumococcal immunization. Conjugate vaccine may improve disease protection, health of infants and young children. Postgrad Med. 2002 Nov;112(5):85-6, 89-90, 93-6.

Since 2000, a new pneumococcal conjugate vaccine has been on the US market, offering immunization against seven serotypes. Its use has the potential to dramatically reduce the incidence of pneumococcal disease and its sequelae in children. Here, the authors review the efficacy, safety, and cost of the new pneumococcal vaccine and offer guidelines on how to incorporate this newer vaccine into today's immunization regimens.

6849.      Weisman LE. Current respiratory syncytial virus prevention strategies in high-risk infants. Pediatr Int. 2002 Oct;44(5):475-80.

Respiratory syncytial virus (RSV) was initially isolated in 1956. Since then it has become recognized as a major pathogen worldwide. It is a ubiquitous pathogen that produces seasonal epidemics. Primary infection occurs in children before 2 years of age. In older children and adults, RSV usually manifests itself as an upper respiratory tract infection. In immunecompromised patients, those with underlying cardiopulmonary disorders, premature infants, and other vulnerable individuals, RSV infection can produce severe bronchiolitis or pneumonia. In recent years we have observed exciting new information about the prevention of serious RSV infection in high-risk infants including infection control practices, active immunity and passive immunity. Two immunoprophylaxis products (RSV i.v. immune globulin and palivzumab) have been developed for clinical use in the prevention of serious RSV infection. Many other agents including vaccines, super monoclonal antibodies, and antivirals are under development. Although clinicians now have the ability to provide their most vulnerable patients with meaningful prevention strategies, much more needs to be done before we can regard RSV as a preventable disease.

6850.      Whitney CG, Pickering LK. The potential of pneumococcal conjugate vaccines for children. Pediatr Infect Dis J. 2002 Oct;21(10):961-70.

In contrast to earlier pneumococcal vaccines, conjugate vaccines hold promise for reducing pneumococcal morbidity and mortality in infants and young children. The first commercially available conjugate vaccine formulation, which targets seven serotypes, was licensed in the US and other countries in 2000; this vaccine is now part of routine infant immunization in the US. Demand has been high and greater than vaccine supply. Clinical trials indicate that conjugate vaccines are highly efficacious against invasive pneumococcal disease and modestly efficacious against otitis media and pneumonia. In carriage studies conjugate vaccines reduced vaccine-type carriage but led to an increase in

carriage of other serotypes. Remaining questions include whether less frequent transmission of vaccine serotypes will mean less disease in unvaccinated children and adults or if nonvaccine serotypes will begin to cause more disease. Monitoring disease burden after widespread use in the US is critical for understanding the effects of the vaccine. In addition making pneumococcal vaccines available for children in developing countries should be a high priority.



  6851.   Allegranzi B, Luzzati R, Luzzani A, Girardini F, Antozzi L, Raiteri R, Di Perri G, Concia E. Impact of antibiotic changes in empirical therapy on antimicrobial resistance in intensive care unit-acquired infections. J Hosp Infect. 2002 Oct;52(2):136-40.

We conducted a one-year prospective study on intensive care unit (ICU)-acquired infections and antimicrobial resistance patterns in an 18-bed medical-surgical ICU of a tertiary-care university hospital. We divided the study into two six-month periods in order to evaluate the impact of antibiotic changes in empirical therapy on antimicrobial resistance profiles of the principal isolated micro-organisms. In the first period no changes were made to the previously applied empirical antibiotic protocol; at the end of this period we found high rates of methicillin resistance (MR) among staphylococci, 93% for Staphylococcus aureus (69 isolates) and 79% for coagulase-negative staphylococci (CNS) (48 isolates), and of multiple drug resistance for Pseudomonas aeruginosa (57 isolates), in particular 67% resistance to piperacillin/tazobactam (PIP/TZ). We therefore decided to substitute PIP/TZ with imipenem in nosocomial pneumonia and with cefepime plus metronidazole in peritonitis. We also considered the previous use of amoxicillin/clavulanate (AM/CL) at admission in critically ill patients inadequate; we therefore advised that no antibiotics should be given unless fever developed and eventually to replace AM/CL with trimethoprim/sulfamethoxazole (TMP/SMX). At the end of this intervention period, we observed a significant decrease of S. aureus MR (93 vs. 73%, P = 0.003) and of P. aeruginosa resistance to PIP/TZ (67 vs. 29%, P < 0.001). A reduction in MR was also seen in CNS (79 vs. 64%, P = 0.09). Other resistance patterns also improved among staphylococci; in contrast P. aeruginosa resistance to imipenem increased in the second period (24 vs. 41%, P = 0.06). A non-premeditated change of antibiotics in empirical therapy, on the basis of detected resistance patterns, provided promising results in reducing some antimicrobial resistance rates. We believe, however, that antibiotic changes must be tailored to local microbiological situation monitoring, and that a repeated rotation is crucial to limit the emergence of new resistance profiles. Furthermore the adoption of this policy should be accompanied by other infection control practices aimed at reducing antimicrobial resistance and nosocomial infection rates. Copyright 2002 The Hospital Infection Society.

6852.  Lorente C, Del Castillo Y, Rello J. Prevention of infection in the intensive care unit: current advances and opportunities for the future. Curr Opin Crit Care. 2002 Oct;8(5):461-4.

Recent studies have contributed to our understanding of the risk factors and the impact of nosocomial infections in the ICU, allowing a more rational approach to the prevention of such infections. Ventilator-associated pneumonia, bloodstream infections, and outbreaks all occur in the presence of artificial devices. High antibiotic pressure, prolonged hospitalization, and the presence of comorbidities facilitate the selection of multiresistant strains in the ICU setting. In clinical practice, prevention is the more effective investment to reduce costs. Potential measures of control should focus on the patient, the microorganisms, and the device. A number of recent studies addressing these issues have been published and will be reviewed in this article.


July 2003


7414.      Agarwal M. New  nuances in the management of nosocomial pneumonia. Hosp Today 2001, 6(11), 691-4.(19812) Vol 38 No1 19 1 Oct 2023

7415.      Agarwal V C. Role of  cephalosprins in the management of  community acquired pneumonia. Hosp Today 2001, 6(10), 605-08 (19814) Vol 38 No1 19 1 Oct 2002

7416.      Akisawa Y, Nishimori I, Taniuchi K, Okamoto N, Takeuchi T, Sonobe H, Ohtsuki Y, Onishi S.  Expression of carbonic anhydrase-related protein CA-RP VIII in non-small cell lung cancer. Virchows Arch. 2003 Jan;442(1):66-70.

Carbonic anhydrase-related protein (CA-RP VIII) lacks a Zn-binding motif which is essential for carbonic anhydrase activity. Therefore, CA-RP VIII is believed to have a no catalytic activity and a new biological property. In the present study, CA-RP VIII expression in non-tumorous lung and non-small cell lung carcinomas was investigated. Little or no expression of CA-RP VIII was observed in human lungs by Northern-blot analysis. Reverse-transcription polymerase chain reaction analysis demonstrated CA-RP VIII mRNA in developing human lungs and, to a lesser extent, in normal lungs. Subsequent immunohistochemical staining revealed that CA-RP VIII was expressed in the pulmonary epithelium in developing lungs; however, CA-RP VIII expression was restricted in bronchial ciliated cells in adult lungs. Neither bronchial gland nor squamous metaplasia of interstitial pneumonia expressed CA-RP VIII. In contrast, CA-RP VIII was strongly expressed in almost all archival lung cancer specimens, which included 24 squamous cell carcinomas, 25 adenocarcinomas, and 6 adenosquamous cell carcinomas. Cancer cells at the front of tumor progression expressed CA-RP VIII in particular abundance. The present findings suggest that CA-RP VIII may play a role in non-small lung cell carcinomas.

7417.      Ansari NA, Kombe AH, Kenyon TA, Mazhani L, Binkin N, Tappero JW, Gebrekristos T, Nyirenda S, Lucas SB.  Pathology and causes of death in a series of human immunodeficiency virus-positive and -negative pediatric referral hospital admissions in Botswana. Pediatr Infect Dis J. 2003 Jan;22(1):43-7.

BACKGROUND: Little is known about causes of death among children seriously affected by the AIDS epidemic in southern African countries. METHODS: Autopsies were performed on 47 children 1 month to 13 years of age in Francistown, Botswana, between July 1997 and July 1998. RESULTS: Median age was 10 months; 68% were HIV-positive. The leading cause of death was respiratory infection, accounting for 29 of 35 (83%) deaths among HIV-positive and 8 of 12 (67%) deaths among HIV-negative children. Among HIV-positive children, Pneumocystis carinii pneumonia (PCP) was responsible for 31% of all deaths and for 48% of deaths in infants < or =1 year. Among children < or =2 years with cough and dyspnea, age < or =1 year, interstitial infiltrate and HIV positivity were highly predictive of PCP (sensitivity, 100%; specificity, 63%). CONCLUSION: Respiratory disease accounted for most deaths in HIV-positive children. Children < or =1 year who are known or suspected to be HIV-positive and who have cough, dyspnea and pulmonary infiltrates should be treated presumptively for PCP.

7418.      Butnor KJ, Sporn TA.   Human parainfluenza virus giant cell pneumonia following cord blood transplant associated with pulmonary alveolar proteinosis. Arch Pathol Lab Med. 2003 Feb;127(2):235-8.

Giant cell pneumonia secondary to human parainfluenza virus 3 has been reported only rarely in immunocompromised hosts. The few cases documented after bone marrow transplant have resulted in significant morbidity and mortality. To our knowledge, this entity has not been described following umbilical cord blood transplant. Pulmonary alveolar proteinosis, a rare condition that has been reported with increasing frequency in association with immunocompromise and infections, has not been documented in the setting of either umbilical cord blood transplant or human parainfluenza viral infection. We report what we believe is the first documented case of giant cell pneumonia caused by human parainfluenza virus 3 in an umbilical cord blood transplant recipient. To our knowledge, a unique associated feature of this case, a pulmonary alveolar proteinosis-like reaction, has not been reported previously in association with human parainfluenza virus pneumonia.

7419.      Cebrian P, Manjon P, Caba P.  Ultrasonography of non-traumatic rupture of the Achilles tendon secondary to levofloxacin. Foot Ankle Int. 2003 Feb;24(2):122-4.

Rupture of Achilles tendon (AT) is an uncommon complication of treatment with fluoroquinolones. We describe a case of bilateral tendinosis and rupture of the right AT in a patient who began levofloxacin treatment for community acquired pneumonia. Sonography showed thickening and hypoecogenicity of both AT and complete rupture and separation of the right Achilles tendon.

7420.      Chmura K, Lutz RD, Chiba H, Numata MS, Choi HJ, Fantuzzi G, Voelker DR, Chan ED.  Mycoplasma pneumoniae antigens stimulate interleukin-8. Chest. 2003 Mar;123(3 Suppl):425S. No abstract available

7421.      Delevaux I, Andre M, Aumaitre O, Begue RJ, Colombier M, Piette JC. Procalcitonin measurement for differential diagnosis between pulmonary embolism and pneumonia. Crit Care Med. 2003 Feb;31(2):661. No abstract available

7422.      Fruchter O, Dragu R.  Images in clinical medicine. A deadly examination. N Engl J Med. 2003 Mar 13;348(11):1016. No abstract available

7423.      Gutierrez F, Masia M, Rodriguez JC, Ayelo A, Soldan B, Cebrian L, Mirete C, Royo G, Hidalgo AM.   Evaluation of the immunochromatographic Binax NOW assay for detection of Streptococcus pneumoniae urinary antigen in a prospective study of community-acquired pneumonia in Spain. Clin Infect Dis. 2003 Feb 1;36(3):286-92.

We evaluated the Binax NOW rapid immunochromatographic membrane test (ICT) for detection of Streptococcus pneumoniae urinary antigen in a population-based prospective study of adults with community-acquired pneumonia (CAP). ICT was performed with urine samples obtained from 452 (91.7%) of 493 patients enrolled. Pneumococcal antigen was detected in 19 (70.4%) of 27 patients with pneumococcal pneumonia. The test results were more frequently positive for patients who had not received antibiotics before testing (26.6% vs. 12.1%; P=.002). Only 16 (10.3%) of 156 samples obtained from patients with nonpneumococcal pneumonia yielded a positive result. Of the 269 patients who had pneumonia with no pathogen identified, antigen was detected in 69 (25.7%). With conventional microbiological criteria used as the "gold standard," the test had a sensitivity  of 70.4% and a specificity of 89.7%. Testing concentrated urine samples with the ICT may be a useful technique for rapid diagnosis of pneumococcal pneumonia in adults with CAP.

7424.      Ishii H, Mukae H, Kadota J, Kaida H, Nagata T, Abe K, Matsukura S, Kohno S.  High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia. Thorax. 2003 Jan;58(1):52-7.

BACKGROUND: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewis(a) (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP. METHODS: Serum and bronchoalveolar lavage (BAL) fluid levels of the above five markers were measured in 57 patients with various forms of ILD (19 with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis), eight patients with the control disease (diffuse panbronchiolitis (DPB)), and nine healthy volunteers. RESULTS: Serum levels of SP-A, SP-D, and KL-6 in patients with UIP and NSIP were significantly higher than in healthy volunteers. In particular, the serum levels of SP-A in patients with UIP were significantly higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95% confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients with UIP were significantly lower than in patients with NSIP (p=0.01, mean difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). CONCLUSION: Serum SP-A levels may be clinically useful as a biomarker to differentiatebetween UIP and NSIP.

7425.      Jacobs RL, Andrews CP. Hypersensitivity pneumonia-nonspecific interstitial pneumonia/fibrosis histopathologic presentation: a study in diagnosis and long-term management. Ann Allergy Asthma Immunol. 2003 Feb;90(2):265-70.

BACKGROUND: Nonspecific interstitial pneumonia/fibrosis (NSIP) has been classified a form of idiopathic interstitial pneumonia/fibrosis. We have shown that cases of NSIP without demonstrable serum precipitins may be caused by inhalation of high levels of mold and/or bacteria in closed environments. OBJECTIVE: We report a patient with a clinical and histopathologic diagnosis of NSIP without serum precipitins caused by a microbial contamination in her home. Her case was converted from an acute to an insidious clinical presentation by inadequate remediation. A prolonged avoidance-challenge technique demonstrated that this case of NSIP was a form of hypersensitivity pneumonia that was reversible by effective remediation. METHODS: The patient was identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and a transbronchial lung biopsy. She was further evaluated with a detailed environmental history, serologic tests, and investigation of the home environment. An environmental avoidance and challenge technique was performed to confirm cause and effect and to determine that remediation had been effective. RESULTS: Review of the biopsy showed NSIP and failed to reveal any non-caseating granuloma formation. Investigation of the home revealed a Cladosporium species contamination of the air conditioning system and Penicillium species beneath an entryway carpet. Serum precipitins to commercial antigens of common mold to the south Texas area were negative. Avoidance and challenge techniques confirmed the home as the causative environment in this case of NSIP. The patient has been free of signs and symptoms and has taken no medication for interstitial lung disease over the past 30 months. CONCLUSIONS: Some cases of NSIP may be caused by inhalation of microbial antigen(s) in a closed environment. An environmental challenge technique was an effective method to determine the causative environment and confirm that remediation had been effective. Inadequate remediation may lead to symptomatic improvement, but may convert a patient from an acute to an insidious presenter. The environmental challenge obviates a need for specific challenges to determine specific causation. Remediation of or moving from an environmental contamination to achieve reversibility or prevent progression was the treatment of choice to avoid use of long-term immunosuppressive agents.

7426.      Kawazu M, Kanda Y, Goyama S, Takeshita M, Nannya Y, Niino M, Komeno Y, Nakamoto T, Kurokawa M, Tsujino S, Ogawa S, Aoki K, Chiba S, Motokura T, Ohishi N, Hirai H.  Rapid diagnosis of invasive pulmonary aspergillosis by quantitative polymerase chain reaction using bronchial lavage fluid.Am J Hematol. 2003 Jan;72(1):27-30.

Polymerase chain reaction (PCR) is a sensitive method for detection of Aspergillus DNA in bronchoalveolar lavage fluid, but it has not yet been able to distinguish infection from contamination. We have established a technique to quantify Aspergillus DNA using a real-time PCR method to resolve this problem, and we report herein a successful application of real-time PCR to diagnose invasive pulmonary aspergillosis by comparing the amount of Aspergillus DNA in bronchial lavage fluid from an affected area to that from an unaffected area. This novel tool will provide rapid, sensitive, and specific diagnosis of pulmonary aspergillosis. Copyright 2002 Wiley-Liss, Inc.

7427.      Kelsberg G, Safranek S.  How accurate is the clinical diagnosis of pneumonia? J Fam Pract. 2003 Jan;52(1):63-4; discussion 64.No abstract available

7428.      Korppi M, Remes S, Heiskanen-Kosma T. Serum procalcitonin concentrations in bacterial pneumonia in children: a negative result in primary healthcare settings. Pediatr Pulmonol. 2003 Jan;35(1):56-61.

A microbe-specific diagnosis in community-acquired pneumonia (CAP) is difficult in children, and studies on nonspecific chest radiographic and host response markers have been inconsistent. Serum procalcitonin (PCT) is a newly recognized, promising marker for differentiating between bacterial and viral infections. Serum PCT was measured by a luminometric assay in 190 children with CAP diagnosed in the primary healthcare setting during a population-based study in a geographically defined population. The pneumococcal, mycoplasma, chlamydia, and viral etiology of infections was studied by an extensive serologic test panel. The median PCT concentrations were 0.47, 0.46, and 0.35 ng/mL in children aged <5 years, 5-9 years, and >/=10 years (P = 0.004). An elevated PCT >1.0 ng/mL was seen in 12.1% and >2.0 ng/mL in only 2.1% of the children. No association was seen between severity (inpatient vs. outpatient care) and etiology of CAP (evidence for pneumococcal, mycoplasma, or chlamydia, vs. viral infection). We conclude that serum PCT measurements have no role in the diagnosis of bacterial CAP in children in primary healthcare settings. Copyright 2003 Wiley-Liss, Inc.

7429.      Koyama , Johkoh T, Honda O, Tsubamoto M, Kozuka T, Tomiyama N, Hamada S, Nakamura H, Akira M, Ichikado K, Fujimoto K, Rikimaru T, Tateishi U, Muller NL.  Chronic cystic lung disease: diagnostic accuracy of high-resolution CT in 92 patients.AJR Am J Roentgenol. 2003 Mar;180(3):827-35.

OBJECTIVE: The objective of this study was to determine whether the various chronic cystic lung diseases can be differentiated on the basis of the pattern and distribution of abnormalities on high-resolution CT. MATERIALS AND METHODS: High-resolution CT scans in 92 patients with chronic cystic lung diseases (18 with pulmonary Langerhans cell histiocytosis, 18 with pulmonary lymphangioleiomyomatosis, 17 with usual interstitial pneumonia, 16 with lymphocytic interstitial pneumonia, 15 with emphysema, and eight with desquamative interstitial pneumonia or respiratory bronchiolitis interstitial lung disease) were retrospectively assessed by two independent observers without knowledge of the clinical or pathologic data. The observers recorded the abnormalities, the most likely diagnosis, and the degree of confidence in that diagnosis. RESULTS: The two observers made a correct first-choice diagnosis in 148 (80%) of 184 interpretations. The correct diagnosis was made in 100% of interpretations of usual interstitial pneumonia, 81% of desquamative interstitial pneumonia or respiratory bronchiolitis interstitial lung disease, 81% of lymphocytic interstitial pneumonia, 77% of emphysema, 72% of lymphangioleiomyomatosis, and 72% of Langerhans cell histiocytosis. The two observers made a diagnosis with a high degree of confidence in 105 (57%) of 184 interpretations. The confident diagnosis was correct in 98 (93%) of 105 interpretations. CONCLUSION: Although various chronic cystic lung diseases often have a characteristic appearance that allows their distinction on high-resolution CT, considerable overlap exists among the CT findings. Therefore, lung biopsy is often required for a definitive diagnosis.

7430.      Kuehnert MJ, Doyle TJ, Hill HA, Bridges CB, Jernigan JA, Dull PM, Reissman DB, Ashford DA, Jernigan DB.  Clinical features that discriminate inhalational anthrax from other acute respiratory illnesses. Clin Infect Dis. 2003 Feb 1;36(3):328-36.

Inhalational anthrax (IA) is a rapidly progressive disease that frequently results in sepsis and death, and prompt recognition is critical. To distinguish IA from other causes of acute respiratory illness, patients who had IA were compared with patients in an ambulatory clinic who had influenza-like illness (ILI) and with hospitalized patients who had community-acquired pneumonia (CAP) at the initial health care visit. Compared with patients who had ILI, patients who had IA were more likely to have tachycardia, high hematocrit, and low albumin and sodium levels and were less likely to have myalgias, headache, and nasal symptoms. Scoring systems were devised to compare IA with ILI or CAP on the basis of strength of association. For ILI, a score of > or =4 captured all 11 patients with IA and excluded 664 (96.1%) of 691 patients with ILI. Compared with patients who had CAP, patients with IA were more likely to have nausea or vomiting, tachycardia, high transaminase levels, low sodium levels, and normal white blood cell counts. For CAP, a score of > or =3 captured 9 (81.8%) of 11 patients with IA and excluded 528 (81.2%) of 650 patients with CAP. In conclusion, selected clinical features of patients with IA differ from those of patients with ILI and are more similar to those of patients with CAP.

7431.      Majeski EI, Harley RA, Bellum SC, London SD, London L. Differential role for T cells in the development of fibrotic lesions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus Acute Respiratory Distress Syndrome.Am J Respir Cell Mol Biol. 2003 Feb;28(2):208-17.

Bronchiolitis obliterans organizing pneumonia (BOOP) and Acute Respiratory Distress Syndrome (ARDS) are two pulmonary diseases with fibrotic components. BOOP is characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intra-alveolar fibrosis. ARDS is a biphasic disease that includes an acute phase, consisting of severe leukocyte infiltration, edema, hemorrhage, and the formation of hyaline membranes, and a chronic phase, which is characterized by persistent intra-alveolar and interstitial fibrosis. CBA/J mice infected with 1 x 10(6) plaque-forming units (pfu) reovirus 1/L develop follicular bronchiolitis and intra-alveolar fibrosis similar to BOOP. In contrast, CBA/J mice infected with 1 x 10(7) pfu reovirus 1/L develop histologic characteristics of ARDS including diffuse alveolar damage, hyaline membranes, and intra-alveolar fibrosis. In this report, we demonstrate a differential role for T lymphocytes in the development of fibrosis associated with BOOP versus ARDS. Neonatally thymectomized CBA/J mice infected with 1 x 10(7) pfu (ARDS) reovirus 1/L still develop the hallmark characteristics of ARDS, including a severe viral pneumonia with cellular infiltrates comprised mainly of macrophages and neutrophils, hyaline membrane formation, and hemorrhage during the acute phase of the disease and persistent intra-alveolar fibrosis during the chronic phase of the disease. In contrast, neonatally thymectomized CBA/J mice infected with 1 x 10(6) pfu (BOOP) reovirus 1/L do not develop intra-alveolar fibrosis associated with BOOP. Therefore, while T cells are necessary for the development of intraluminal fibrosis associated with BOOP, they are not necessary for the development of intraluminal fibrosis associated with ARDS. Furthermore, we suggest that interferon-gamma plays a key role in the fibrotic process and that elevated levels of interferon-gamma are associated with a continuum from least to more severe fibrosis.

7432.      Mathur N B, Garb K, Kumar S. Respiratory  distress in neonates with special reference to pneumonia. Indian Pediat 2002, 39(6), 529-37. (21946) Vol 38, No 21, Nov 2002

7433.      Metlay JP, Fine MJ.  Testing strategies in the initial management of patients with community-acquired pneumonia. Ann Intern Med. 2003 Jan 21;138(2):109-18.

The initial management of patients suspected of having community-acquired pneumonia is challenging because of the broad range of clinical presentations, potential life-threatening nature of the illness, and associated high costs of care. The initial testing strategies should accurately establish a diagnosis and prognosis in order to determine the optimal treatment strategy. The diagnosis is important in determining the need for antibiotic therapy, and the prognosis is important in determining the site of care. This paper reviews the test characteristics of the history, physical examination, and laboratory findings, individually and in combination, in diagnosing community-acquired pneumonia and predicting short-term risk for death from the infection. In addition, we consider the implications of these test characteristics from the perspective of decision thresholds. The history and physical examination cannot provide a high level of certainty in the diagnosis of community-acquired pneumonia, but the absence of vital sign abnormalities substantially reduces the probability of the infection. Chest radiography is considered the gold standard for pneumonia diagnosis; however, we do not know its sensitivity and specificity, and we have limited data on the costs of false-positive and false-negative results. In the absence of empirical evidence, the decision to order a chest radiograph needs to rely on expert opinion in seeking strategies to optimize the balance between harms and benefits. Once community-acquired pneumonia is diagnosed, a combination of history, physical examination, and laboratory items can help estimate the short-term risk for death and, along with the patient's psychosocial characteristics, determine the appropriate site of treatment.

7434.      Murdoch DR.  Diagnosis of Legionella infection. Clin Infect Dis. 2003 Jan 1;36(1):64-9. 

Legionellae, which are important causes of pneumonia in humans, continue to be incorrectly labeled as exotic pathogens. The ability to diagnose Legionella infection is limited by the nonspecific nature of clinical features and the shortcomings of diagnostic tests. Despite recent improvements, existing diagnostic tests for Legionella infection either lack sensitivity for detecting all clinically important legionellae or are unable to provide results within a clinically useful time frame. Understanding local Legionella epidemiology is important for making decisions about whether to test for Legionella infection and which diagnostic tests to use. In most situations, the use of both the urinary antigen test plus sputum culture is the best diagnostic combination. Polymerase chain reaction (PCR) is a promising tool, but standardized assays are not commercially available. Further work needs to focus on the development of urinary antigen tests assays that detect a wider range of pathogenic legionellae and on the development of standardized PCR assays.

7435.      Reading M.  Chest X-ray quiz. Right middle lobe consolidation/atelectasis from pneumonia. Intensive Crit Care Nurs. 2003 Feb;19(1):41, 42.No abstract available

7436.      Rello J, Bodi M, Mariscal D, Navarro M, Diaz E, Gallego M, Valles J.  Microbiological testing and outcome of patients with severe community-acquired pneumonia.Chest. 2003 Jan;123(1):174-80.

STUDY OBJECTIVES: The study documents the impact of microbiological investigations on therapeutic decisions and outcome in patients with severe community-acquired pneumonia (SCAP). DESIGN: Retrospective analysis of prospectively collected data. SETTING: ICUs in two teaching Spanish hospitals. PATIENTS: Two hundred four consecutive patients admitted to intensive care with SCAP. INTERVENTIONS: None. Measurements and results: One hundred six patients required intubation, while 98 other patients did not (81 of these patients were managed with noninvasive mechanical ventilation). The microbiologic diagnosis was established in 57.3% of patients. The most common pathogens were Streptococcus pneumoniae, Legionella pneumophila, and Haemophilus influenzae. Pseudomonas (6.6.% vs 1.0%, p < 0.05) and Legionella (15.1% vs 7.1%, p < 0.05) were more frequently documented in intubated patients. Overall mortality was 23.5% (44.3% in intubated patients), with S pneumoniae (n = 7), Pseudomonas aeruginosa (n = 7), and L pneumophila (n = 5) being the most common lethal pathogens. Bacteriological investigation led to changes in antibiotic prescription in 41.6% of patients, including 11 patients (5%) in whom initial treatment was ineffective against the microbial isolates. The most frequent reason for changes was simplification of therapy in 65 episodes (31.8%). CONCLUSIONS: We conclude that microbiological testing is fully justified in patients with SCAP, because identifying the causative agent and adjusting treatment both impact on patient outcome. Our findings suggest that intubated patients should be empirically treated for Pseudomonas and Legionella while awaiting bacteriology results.

7437.      Sarper N, Ipek IO, Ceran O, Karaman S, Bozaykut A, Inan S. A rare syndrome in the differential diagnosis of hepatosplenomegaly and pancytopenia: report of identical twins with Griscelli disease. Ann Trop Paediatr. 2003 Mar;23(1):69-73.

White, identical twin boys aged 3 months were referred to our centre with persisting fever, mouth ulcers, hepatosplenomegaly, pancytopenia and failure to thrive. The parents were first cousins and there was a history of a sibling with similar manifestations who had died. The infants had silvery-grey hair and pigment clumps on the hair shafts, and skin biopsy showed accumulation of melanocytes on melanosomes. Bone marrow revealed hypercellularity and haemophagocytosis. HLH-94 chemotherapy (initial therapy with daily dexamethasone and etoposide, maintenance with dexamethasone pulses, etoposide and cyclosporin A) was started. Though partial haematological remission was achieved, one of the boys died on the 34th day following aspiration pneumonia. No pathogen could be identified. The second boy responded to therapy but had a haematological relapse and died 68 days after first being admitted. Genetic study revealed a 5 bp deletion in the RAB27A gene (510 del AAGCC in exon 5). Transient haematological  remission can be achieved with chemotherapy but allogeneic bone marrow transplantation is the only curative therapy in Griscelli disease, as in other familial haemophagocytic syndromes. Identification of the mutation also provides an opportunity for prenatal diagnosis.

7438.      Sirvent JM, Vidaur L, Gonzalez S, Castro P, de Batlle J, Castro A, Bonet A. Microscopic examination of intracellular organisms in protected bronchoalveolar mini-lavage fluid for the diagnosis of ventilator-associated pneumonia. Chest. 2003 Feb;123(2):518-23.

STUDY OBJECTIVES: To assess the cutoff percentage of cells containing intracellular organisms (ICOs) in the microscopic examination of mini-lavage fluid for the diagnosis of ventilator-associated pneumonia (VAP), and to study the accuracy of this diagnostic procedure on patients who have received previous antibiotic therapy (AT). DESIGN: Prospective clinical investigation. SETTING: The medico-surgical ICU of a university hospital. PATIENTS: Eighty-two patients who fulfilled the clinical criteria of first episode of VAP. INTERVENTIONS: Lower airway secretion samples were obtained by a nonbronchoscopic protected bronchoalveolar mini-lavage (mini-PBAL). Measurements and results: A total of 82 mini-PBALs were performed. The fluid obtained was divided into two samples. The first sample underwent direct microscopic examination using centrifugal cytology and Giemsa stain in order to determine the percentage of cells containing ICOs. The second sample was processed for Gram stain and quantitative cultures. VAP was the final diagnosis in 65 patients based on the mini-PBAL results obtained in the quantitative cultures. At least one bacterial species grew in a significant concentration (> or = 10(3) cfu/mL). The mini-PBAL was performed on 42 patients during AT (> or = 24 h of effective AT at the time of diagnostic procedure) and on another 40 patients with no AT (No AT). The results of the quantitative cultures were compared with the percentage of cells containing ICOs using a receiver operator characteristic (ROC) curve. The cutoff point of > or = 2% of cells containing ICOs had the highest sensitivity (80%) and specificity (82%) in the studied population (area under the ROC curve [AUC], 0.83; 95% confidence interval [CI], 0.70 to 0.90). In patients receiving AT, the sensitivity was 70% and specificity was 75% (AUC, 0.73; 95% CI, 0.58 to 0.90); and in No AT-group patients sensitivity was 88% and specificity was 100% (AUC, 0.92; 95% CI, 0.84 to 1.0). The comparative analysis of both ROC curves was statistically significant (p = 0.04). CONCLUSIONS: The cutoff point of > or = 2% of cells containing ICOs has the highest sensitivity and specificity in the microscopic examination of mini-lavage fluid for the diagnosis of VAP. However, sensitivity is too low to be clinically useful. The direct examination of mini-PBAL fluid is less accurate when previous AT has been administered.

7439.      Spuck S, Schaaf B, Wiedorn KH, Hansen F, Vollmer E, Dalhoff K, Braun J.  G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils. Respir Med. 2003 Jan;97(1):51-8.

In severe pneumonia, the application of granulocyte-colony stimulating factor (G-CSF) was associated with reduced complications possibly by an induction of anti-inflammatory cytokines. It is not clear, whether G-CSF induces interleukin-10 (IL-10) synthesis in neutrophils. In a randomized study, 15 patients with severe community acquired pneumonia were treated either by a single dose of G-CSF and antibiotic therapy (n=8) or antibiotics alone (n=7). Messenger ribonucleic acid (mRNA) expression of IL-10 and tumor necrosis factor alpha of peripheral blood leukocytes was measured using in-situ hybridization (ISH) and reverse-transcription-polymerase-chain-reaction (RT-PCR). In addition, the cytokine release of lipopolysaccharide (LPS)-stimulated whole blood was measured by ELISA. We detected increased IL-10 mRNA by ISH (140 +/- 8% vs. –11 +/- 5%, P<0.01) and RT-PCR (126 +/- 16% vs. -28 +/- 3%, P<0.01) in the G-CSF-treated group only. In contrast, LPS-stimulated whole blood cells in vitro released significantly less IL-10 compared to the control group (-38.2 +/- 97 vs. -14.8 +/- 6 pg/ml, P<0.02). There was no significant effect on IL-10 serum protein levels and the TNF-alpha release and expression. IL-10 mRNA was detected predominantly in cluster designation 66b (CD66b) positive nucleated blood cells indicating that polymorphonuclear leukocytes are the main source of IL-10 expression after G-CSF stimulation. G-CSF induces transcription of IL-10 mRNA in neutrophils without increased release. This may be due to posttranscriptional effects.

7440.      Subha A, Ananthan S. Extended spectrum beta lactamase (ES L) mediated resistance to third generation cephalosporins among Klebsiella pneumoniae in Chenni. India J med Micribiol 2002, 20(2), 92-5.(21786) Vol 38, No. 21, 1 Nov 2002.

7441.      Tokuda Y, Nakazato N, Stein GH. Pupillary evaluation for differential diagnosis of coma. Postgrad Med J. 2003 Jan;79(927):49-51.

OBJECTIVES: To determine the usefulness of bedside evaluation of pupils in determining the aetiology of coma by adopting a probabilistic approach. PATIENTS AND METHODS: One hundred and fifteen consecutive patients presenting with coma were enrolled in this prospective cohort during the 12 month study period in the emergency room of a community teaching hospital. Patients underwent structured clinical examinations and laboratory and imaging tests. Assignment of aetiology of coma was based on strict adherence to predetermined criteria and achieved by consensus of the two physician investigators. One year follow up was obtained in all patients. RESULTS: Aetiology of coma was determined in 98% of the patients. It was metabolic in 69 patients (60%) and structural in 46 patients (40%). Metabolic causes included drug overdose, acute alcohol intoxication, hypoglycaemia, sepsis, and pneumonia. Structural causes included intracerebral haemorrhage, subarachnoid haemorrhage, cerebral infarction, subdural haematoma, and epidural haematoma. Multivariate logistic regression analysis showed light reflex loss (likelihood ratio for positive test result 3.59) and anisocoria (likelihood ratio for positive test result 9.0) as independent predictors of structural origin. CONCLUSIONS: In this prospective study of patients presenting to the emergency room of a community based teaching hospital with coma, in about 60% the coma is of metabolic origins and in about 40% of structural origins. Light reflex loss and anisocoria suggest a structural aetiology.

7442.      van Buiren M, Uhl M.   Images in clinical medicine. Bilateral striatal necrosis associated with Mycoplasma pneumoniae infection. N Engl J Med. 2003 Feb 20;348(8):720. No abstract available.

7443.      Viguier M, Fouere S, de la Salmoniere P, Rabian C, Lebbe C, Dubertret L, Morel P, Bachelez H.   Peripheral blood lymphocyte subset counts in patients with dermatomyositis: clinical correlations and changes following therapy. Medicine (Baltimore). 2003 Mar;82(2):82-6.

Lymphocytopenia has been reported in patients with connective tissue diseases, including dermatomyositis (DM). However, the risk of infectious complications and the changes of lymphocytic subsets during treatment have been poorly investigated in these patients. We investigated the alterations of peripheral blood lymphocyte counts in patients with DM. A retrospective analysis was conducted in patients with an ascertained diagnosis of DM admitted from 1994 to 2000 in both departments of Dermatology of the Saint-Louis Hospital in Paris. All patients had a peripheral blood absolute lymphocyte count available before therapy. From an initial set of 63 patients, 47 were included in the study. The median absolute lymphocyte count was 888/mm(3) (range, 400-4,070). Low peripheral blood CD4+ and CD8+ T-cell and B-cell counts were consistent findings (median CD4+: 382/mm(3); CD8+: 211/mm(3); CD19+: 122/mm(3)). There was a significant increase in lymphocyte count after 1 month (p < 0.0001), 3-6 months (p = 0.001), and 6-12 months (p = 0.0005) of corticosteroid treatment. Infectious events, mainly pneumonia (PCP), occurred in 12 patients. Their initial lymphocyte count was lower than that of patients who did not develop infections (p = 0.0001). These results support the high prevalence of lymphocytopenia in patients with DM and emphasize the risk for opportunistic infections, mainly PCP, in these patients. Further studies are warranted to evaluate the risk/benefit balance of PCP prophylaxis in patients with DM and severe lymphocytopenia.

7444.      Wang CL, Wu YT, Liu CA, Lin MW, Lee CJ, Huang LT, Yang KD.  Expression of CD40 ligand on CD4+ T-cells and platelets correlated to the coronary artery lesion and disease progress in Kawasaki disease. Pediatrics. 2003 Feb;111(2):E140-7.

OBJECTIVE: Kawasaki disease (KD) is an acute febrile vasculitic syndrome in children. CD40 ligand (CD40L) has been implicated in certain types of vasculitis. We proposed that CD40L expression might be correlated with coronary artery lesions in KD. METHODS: Blood samples were collected from 43 patients with KD before intravenous immunoglobulin (IVIG) treatment and 3 days afterward. Forty-three age-matched febrile children with various diseases were studied in parallel as controls. CD40L expression on T-cells and platelets were detected by flow cytometry, and soluble CD40L (sCD40L) levels were measured by enzyme-linked immunosorbent assay. RESULTS: We found that CD40L expression on CD4(+) T-cells was significantly higher in patients with KD than in the febrile control (FC) group (28.69 +/- 1.17% vs 4.37 +/- 0.36%). CD40L expression decreased significantly 3 days after IVIG administration (28.69 +/- 1.17% vs 13.53 +/- 0.55%). CD40L expression on platelets from patients with KD was also significantly higher than in the FC group (8.20 +/- 0.41% vs 1.26 +/- 0.12%) and decreased after IVIG therapy. sCD40L levels were also significantly higher in KD patients with those of FC (9.69 +/- 0.45 ng/mL vs 2.25 +/- 0.19 ng/mL) but were not affected by IVIG treatment 3 days afterward (9.69 +/- 0.45 ng/mL vs 9.03 +/- 0.32 ng/mL). More interesting, we found that in KD patients, CD40L expression on CD4(+) T-cells and platelets but not on CD8(+) T-cells or sCD40L was correlated with the occurrence of coronary artery lesions. CONCLUSIONS: CD40L might play a role in the immunopathogenesis of KD. IVIG therapy might downregulate CD40L expression, resulting in decrease of CD40L-mediated vascular damage in KD. This implicates that modulation of CD40L expression may benefit to treat KD vasculitis.

7445.      Waterer GW.  The diagnostic dilemma in suspected ventilator-associated pneumonia: one size will never fit all. Chest. 2003 Feb;123(2):335-7.No abstract available

7446.      Wu CL, Lee YL, Chang KM, Chang GC, King SL, Chiang CD, Niederman MS.  Bronchoalveolar interleukin-1 beta: a marker of bacterial burden in mechanically ventilated patients with community-acquired pneumonia. Crit Care Med. 2003 Mar;31(3):812-7.

OBJECTIVE: To assess the relationship between concentrations of bronchoalveolar cytokines and bacterial burden (quantitative bacterial count) in intubated patients with a presumptive diagnosis of community-acquired pneumonia. DESIGN: A cross-sectional and clinical investigation.SETTING Medical/surgical and respiratory intensive care unit of a tertiary 1,200-bed medical center. PATIENTS: According to the time course of community-acquired pneumonia at the time of study with bronchoalveolar lavage, 69 mechanically ventilated patients were divided into three subgroups: primary (n = 11), referral (n = 23), and treated (n = 35) community-acquired pneumonia. INTERVENTIONS: Bronchoalveolar lavage was performed in the most abnormal area on chest radiograph by fiberoptic bronchoscope. Bronchoalveolar lavage fluid was processed for quantitative bacterial culture. The concentrations of bronchoalveolar lavage cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and interleukin-10) also were measured. MEASUREMENTS AND MAIN RESULTS: Thirty-two  patients had a positive bacterial culture (bronchoalveolar lavage > or = 10 colony-forming units/mL)., and made up 76% of pathogens recovered at high concentrations. The concentrations of bronchoalveolar lavage interleukin-1 beta were 199.1 +/- 32.1 and 54.9 +/- 13.0 pg/mL (mean +/- se) in the patients with positive and negative bacterial culture, respectively (p < .001). Bronchoalveolar lavage interleukin- 1 beta was significantly higher in the patients with a high bacterial burden (p < .001), with mixed bacterial infection (p < .001), and with pneumonia (p < .001), compared with values in patients without these features. The relationship between bacterial load and concentrations of bronchoalveolar lavage interleukin-1 beta was very strong in the patients with primary and referral community-acquired pneumonia but was borderline in treated community-acquired pneumonia. CONCLUSIONS: The common pathogens were similar to the core pathogens of hospital-acquired pneumonia, probably due to antibiotic effects, delayed sampling, and superimposed nosocomial infection. Since the concentration of bronchoalveolar lavage interleukin-1 beta was correlated with bacterial burden in the alveoli, it may be a marker for progressive and ongoing inflammation in patients who have not responded to pneumonia therapy and who have persistence of bacteria in the lung.

7447.      Yamada S, Kameyama T, Nagaya S, Hashizume Y, Yoshida M.  Relapsing herpes simplex encephalitis: pathological confirmation of viral  reactivation. J Neurol Neurosurg Psychiatry. 2003 Feb;74(2):262-4.

This case is reported to raise awareness of herpes simplex encephalitis as a persisting brain disorder. A 66 year old immunocompetent man developed status epilepticus and died of pneumonia in the course of progressive hemiparesis, cognitive decline, and atrophy of the brain over a five year period after herpes simplex encephalitis. In addition to a completely destroyed left temporal lobe, necropsy revealed active encephalitis consisting of necrosis and lymphocyte infiltration with a large number of intranuclear inclusions in the neurones and glial cells in the markedly oedematous parenchyma of the right frontal and parietal lobes. Herpes simplex virus type 1 (HSV-1) antigen was detected by immunohistochemistry, HSV-1 DNA by in situ hybridisation, and herpes simplex virus nucleocapsids by electronmicroscopy. These clinical and pathological findings suggest that direct viral reactivation might result in a relapse of herpes simplex encephalitis, causing progressive clinical deterioration associated with the persistence of HSV-1 in the brain. This is the first case report demonstrating HSV-1 antigen, HSV-1 DNA, and herpes simplex virus nucleocapsids in a case of relapsing herpes simplex encephalitis.


7448.      Buckingham SC, Crouse DT, Knapp KM, Patrick CC. Pneumonitis associated with Ureaplasma urealyticum in children with cancer. Clin Infect Dis. 2003 Jan 15;36(2):225-8.

We describe 3 pediatric patients with cancer who had clinical and radiographic evidence of pneumonitis and for whom cultures of bronchoalveolar lavage fluid specimens yielded Ureaplasma urealyticum. Two of the patients died; for the surviving patient, clinical improvement coincided temporally with administration of erythromycin. Immunocompromised patients with pneumonitis of unclear etiology should have respiratory secretions cultured for mycoplasmas and should receive empiric therapy that includes a macrolide antibiotic.

7449.      Bufler P, Schmidt B, Schikor D, Bauernfeind A, Crouch EC, Griese M.  Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide. Am J Respir Cell Mol Biol. 2003 Feb;28(2):249-56.

We investigated the role of the surfactant proteins (SPs) A and D in the pulmonary immune defense of nonmucoid strains of Pseudomonas aeruginosa, the most etiologic agents of nosocomial Pseudomonas pneumonia. We first examined the interactions of recombinant human SP-D dodecamers and purified natural or recombinant human SP-A with two smooth, and two rough, clinical isolates of nonmucoid P. aeruginosa. SP-D bound to all four isolates, but agglutinated only one rough and one smooth strain. SP-D functioned as an opsonin to enhance the uptake of all four strains by the human monocytic cell line Mono Mac 6 (MM6). SP-D also enhanced tumor necrosis factor-alpha secretion by MM6 cells in response to purified lipopolysaccharide (LPS) isolated from the rough, but not the smooth, strains. Although SP-A bound to all four strains, it did not cause bacterial aggregation or enhance uptake. It showed small but statistically significant inhibitory effects on the cytokine response of MM6 cells to one strain of smooth organisms, but did not significantly alter the response to purified LPS. This study in combination with previously published data strongly suggests that SP-D may play important roles in the local innate pulmonary defense against nonmucoid P. aeruginosa of diverse LPS phenotypes, and preferentially augments the cellular response to rough P. aeruginosa endotoxin.

7450.      Cyranoski D.  Health labs focus on mystery pneumonia.Nature. 2003 Mar 20;422(6929):247. No abstract available

7451.      Dumke R, Catrein I, Pirkil E, Herrmann R, Jacobs E.  Subtyping of Mycoplasma pneumoniae isolates based on extended genome sequencing and on expression profiles. Int J Med Microbiol. 2003 Feb;292(7-8):513-25.

Mycoplasma pneumoniae isolates from patients, collected over a period of 12 years in Germany, were characterized by various methods (parameters) including multilocus sequence typing, restriction fragment length polymorphisms, Western blotting with mono-specific antibodies directed against selected proteins or with polyspecific antibodies directed against the Triton X-114-soluble protein  fraction, and two-dimensional gel electrophoresis. The results for 91 isolates from Germany, which were complemented with 14 isolates from the USA and 10 isolates from France, clearly showed that M. pneumoniae is a highly uniform species and that most of the isolates could be assigned to one of the two subtypes 1 and 2. The members of one subtype differ from the other with respect to the sequence of the P1 gene, the ORF6 gene, the P65 gene, and by a typical DNA restriction fragment pattern. We observed four isolates (variants), which seemed identical by the above mentioned criteria, but did not belong to either one of the two subtypes. They showed most of the subtype 2-specific features, but differed in the sequence of the P1 gene and showed a variation in the restriction fragment pattern. The appearance of subtype 1 or 2 over the last 12 years in Germany showed a dominance of subtype 1 between 1989 and 1996 and a dominance of subtype 2 between 1997 and 1998. The variant (neither subtype 1 nor subtype 2) was only detected in 1991 and 1995 but it had no epidemiological consequences.

7452.      Gallagher PM, Lowe G, Fitzgerald T, Bella A, Greene CM, McElvaney NG, O'Neill SJ.  Association of IL-10 polymorphism with severity of illness in community acquired pneumonia. Thorax. 2003 Feb;58(2):154-6.

BACKGROUND: The influence of genetic polymorphisms of interleukin (IL)-10, tumour necrosis factor (TNF)-alpha, and IL-6 gene promoters on severity of systemic inflammatory response syndrome (SIRS) associated with community acquired pneumonia (CAP) was studied. METHODS: Using PCR-RFLP analysis we analysed a -1082G/A single nucleotide polymorphism (SNP) of the anti-inflammatory IL-10 gene, a -308G/A SNP of the pro-inflammatory TNF-alpha gene and a -174G/C SNP of the IL-6 gene. Illness severity was stratified according to SIRS score, calculated by presence of up to four physiological indices: temperature, white blood cell count, heart rate and respiratory rate (non-SIRS, SIRS 2, SIRS 3, and SIRS 4). RESULTS: A statistically significant stepwise increase in frequency of the IL-10 G allele, associated with higher expression of the gene, was observed in patients with increasing severity of illness from non-SIRS (n=19) to SIRS 2 (n=17), SIRS 3 (n=33) and SIRS 4 (n=24).  This was primarily due to a higher frequency of the GG genotype with increasing severity from non-SIRS through to SIRS 4. IL-10 G allele frequency was also increased in patients who died as a result of CAP (n=11) compared with CAP survivors (n=82) (p=0.01). No association was seen between the TNF-alpha -308G/A and IL-6 -174G/C SNPs and disease. Additionally, no interaction between all three SNP genotypes and disease severity was observed. CONCLUSIONS: A polymorphism affecting IL-10 expression may influence the severity of illness in patients with CAP.

7453.      Huang CF, Wang CL, Huang YF, Hsieh KS, Yang KD.  Hyper-IgM syndrome complicated with interstitial pneumonia and peritonitis.Chang Gung Med J. 2003 Jan;26(1):53-9.

Hyper-IgM syndrome (HIM) is a rare disorder resulting from mutation in the CD40 ligand (CD40L) gene. This defect is associated with normal or elevated serum level of IgM and with low to undetectable levels of serum IgG, IgA, IgE. This case of HIM with CD40L deficiency was proven by flow cytometry but initially presented as interstitial pneumonia. Pneumocystis carinii pneumonia was highly suggested. After intravenous immunoglobulin and trimethoprim-sulfamethoxazole treatment, his lung condition improved. However, peritonitis developed and surgical intervention was performed. Ileum perforation and intestinal lymphoproliferation from a pathologic specimen were noted. Although peritonitis is extremely rare in patients with HIM, this report indicates that peritonitis which results from intestinal lymphoproliferation may be a manifestation of HIM.

7454.      Lanchou J, Corbel M, Tanguy M, Germain N, Boichot E, Theret N, Clement B, Lagente V, Malledant Y. Imbalance between matrix metalloproteinases (MMP-9 and MMP-2) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in acute respiratory distress syndrome patients. Crit Care Med. 2003 Feb;31(2):536-42.

OBJECTIVE: Matrix metalloproteinases (MMPs) are known to be involved in degradation of extracellular matrix. We aimed to assess the role of MMPs and their natural inhibitors (TIMPs) in the genesis and the evolution of acute respiratory distress syndrome (ARDS). DESIGN: Prospective, clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-one patients were assigned to three different groups: Group 1 patients developed ARDS that rapidly resolved in <4 days; Group 2 patients developed ARDS lasting >8 days; Group 3 (control group) patients had clinical criteria for hospital-acquired pneumonia without ARDS. INTERVENTION: Bronchoalveolar lavages were performed on day 0 of the onset of ARDS and on days 4, 8, and 12 for unresolving ARDS. For group 3, the bronchoalveolar lavages were performed on day 0 of the pneumonia. On these bronchoalveolar lavage fluids, we measured the amount of MMP-9 and -2 and their inhibitors TIMP-1 and -2. MEASUREMENTS AND MAIN RESULTS: The amount of MMP-9 measured by enzyme-linked immunosorbent assay was significantly lower in the bronchoalveolar lavages from patients with ARDS (group 1 and group 2) compared with the control group (p <.01) throughout the study. The ratio MMP-9/TIMP-1 was also significantly smaller and was less than one in the two ARDS groups (p <.05) compared with the control group (group 3), where this ratio was greater than one. In the second bronchoalveolar lavages, this ratio was greater than one only in the ARDS group that rapidly resolved (group 1), whereas it stayed less than one when the ARDS was lasting (group 2). Concerning the quantity of MMP-2 and the ratio MMP-2/TIMP-2, there was no statistical difference between the three groups throughout the study. Using zymography, there was no significant difference in the amounts of active and latent MMP-9 between the three groups. Moreover, no significant difference in the quantity of latent and active MMP-2 in the three groups was noted. CONCLUSION: These results suggest that the MMP-9 level and MMP-9/TIMP-1 ratio play a role in the pathogenesis of ARDS and, namely, the imbalance between MMP-9 and TIMP-1 would participate in airway remodeling leading to either short- or long-course ARDS. The ratio MMP-9/TIMP-1 could be a predictive factor of the ARDS evolution.

7455.      Miller DM, Light D.  Laboratory and clinical comparisons of the Streamlined Liner of the Pharynx Airway (SLIPA) with the laryngeal mask airway. Anaesthesia. 2003 Feb;58(2):136-42.

The Streamlined Liner of the Pharynx Airway (SLIPA) is a new inexpensive disposable supraglottic airway designed to seal without the use of an inflatable cuff. It comprises a hollow blow-moulded soft plastic airway shaped to form a seal in the pharynx. Being hollow, liquid entrapment is possible and this may provide effective protection against aspiration. A model silicone rubber pharynx with an 'oesophageal' tube for injecting volumes of regurgitant liquid was designed to evaluate the SLIPA and the standard and ProSeal laryngeal mask airways during positive-pressure ventilation. A linear relationship between the volume 'regurgitated' and the volume 'aspirated' was found with the laryngeal mask airway and the ProSeal laryngeal mask airway with the drainage tube clamped. Both the ProSeal laryngeal mask airway with an open drainage tube and the SLIPA, but not the standard laryngeal mask airway, provided effective protection against 'aspiration' during positive-pressure ventilation using the model. In a clinical study, 120 patients were randomly allocated to receive controlled ventilation of the lungs via the standard laryngeal mask airway or the SLIPA. Both devices were equally easy to insert and satisfactory for airway management.

7456.      Neve R, Biswas S, Dhir V, Mohandas KM, Kelkar R, Shukla P, Jagannath P.  Bile cultures and sensitivity patterns in malignant obstructive jaundice. Indian J Gastroenterol. 2003 Jan-Feb;22(1):16-8.

BACKGROUND: Bactibilia is one of the important factors in the development of postoperative septic complications. We undertook this retrospective analysis to identify the organisms present in bile and their antibiotic susceptibility patterns in patients with malignant obstructive jaundice. METHODS: Bile specimens were obtained during endoscopic cholangiography (ERC; n=65), by flushing biliary stents (n=15), intra-operatively before incising the common bile duct (n=7) or during percutaneous transhepatic biliary drainage (PTBD; n=1). Eighty-eight samples from 65 consecutive patients were analyzed for their bacterial spectrum and sensitivity to antibiotics. Concomitant septic complications such as wound infection and cholangitis were also assessed. RESULTS: Of 65 patients (hilar block 39, distal block 26), 17 (26.1%) had bactibilia at initial ERCP; in addition, 3 of 7 bile specimens obtained during surgery, one collected during PTBD, and 13 of 15 stent flushings grew bacterial organisms. Cholangitis developed in 15 patients (12 with hilar block, 3 with distal block). Blood cultures were positive in 3 cases, and initial bile culture was positive in four patients with cholangitis. The most commonly found organisms were Escherichia coli (36.6%), Klebsiella pneumonia (18.3%), Pseudomonas aeruginosa (8.3%), Proteus vulgaris (8.3%) and coagulase-negative staphylococci (8.3%). The organisms found on ERC were similar to those found at wound cultures in 3 of the 4 cases who developed wound infection. Amikacin, gentamicin, cefotaxime, ceftazidime, and cefoperazone-sulbactam combination showed good activity against E. coli and K. pneumonia. CONCLUSION: Approximately one-fourth of patients with malignant obstructive jaundice have positive bile cultures at initial ERC. Post-ERC cholangitis is common in hilar blocks.

7457.      Safdar A, Armstrong D, Murray HW.  A novel defect in interferon-gamma secretion in patients with refractory nontuberculous pulmonary mycobacteriosis. Ann Intern Med. 2003 Mar 18;138(6):521.No abstract available

7458.      Struve C, Forestier C, Krogfelt KA. Application of a novel multi-screening signature-tagged mutagenesis assay for identification of Klebsiella pneumoniae genes essential in colonization and infection. Microbiology. 2003 Jan;149(Pt 1):167-76.

Klebsiella pneumoniae is a common cause of urinary tract infections (UTIs) and pneumonia, especially in immunocompromised individuals. Epidemiological studies have revealed that K. pneumoniae infections are frequently preceded by gastrointestinal colonization and the gastrointestinal tract is believed to be the most important reservoir for transmission of the bacteria. To identify genes involved in the ability of K. pneumoniae to colonize the intestine and infect the urinary tract, a novel multi-screening signature-tagged mutagenesis (MS-STM) assay was implemented. In the MS-STM assay, PCR-amplified tags present in the inoculum as well as recovered pools from each infection model are simultaneously subjected to hybridization using each specific tag as a probe. Therefore, screenings of a mutant library in more than one infection model is significantly eased compared to the traditional signature-tagged mutagenesis methodology. From a total of 1,440 K. pneumoniae transposon mutants screened, 13 mutants were identified as attenuated in intestinal colonization as well as the UTI model. In addition, six mutants attenuated only in the UTI model were identified. Transposon insertion sites in attenuated mutants were, among others, in genes encoding well-known K. pneumoniae virulence factors such as lipopolysaccharide and capsule, as well as in genes of unknown function.

7459.      Togo S, Shimokawa T, Fukuchi Y, Ra C.  Alternative splicing of myeloid IgA Fc receptor (Fc alpha R, CD89) transcripts in inflammatory responses.FEBS Lett. 2003 Jan 30;535(1-3):205-9.

More than 10 splice variants of the Fc receptor for IgA (Fc alpha R, CD89) have been identified in human myeloid cells. In this study, we quantified Fc alpha R splice transcripts Delta EC2 and Delta 66 EC2, which lack the entire and a part of the homologous immunoglobulin-like extracellular domain 2 (EC2), respectively. Tumor necrosis factor-alpha was found to specifically increase the ratio of Delta EC2 to the wild type CD89 in neutrophils and conversely decrease the Delta EC2 ratio in monocytes. We also observed a significant decrease in the neutrophil Delta EC2/CD89 ratio in pneumonia patients. These results suggest that Delta EC2 is differentially regulated and could be involved in immunoregulation of IgA-mediated host defense.

7460.      Wilson DP, Timms P, McElwain DL.  A mathematical model for the investigation of the Th1 immune response to Chlamydia trachomatis. Math Biosci. 2003 Mar;182(1):27-44.

Chlamydia are bacterial pathogens of humans and animals causing the important human diseases trachoma, sexually transmitted chlamydial disease and pneumonia. Of the human chlamydial diseases, sexually transmitted disease caused by Chlamydia trachomatis is a major public health concern. Chlamydia trachomatis replicates intracellularly and is characterised by a complex developmental cycle. Chlamydia is susceptible to humoral and cell-mediated immunity. Here we  investigate the Th1 cell-mediated immune response against Chlamydia-infected cells as the response changes over the chlamydial developmental cycle. We suggest a form for the immune response over one developmental cycle by modelling the change in the number of intracellular chlamydial particles and assume peptides are presented in proportion to the number of replicating forms of chlamydial particles. We predict, perhaps non-intuitively, that persistent Chlamydia should be induced and forced not to return to the lytic cycle. We also suggest that extending the length of the time of the lytic cycle will effectively decrease the required efficacy of the Th1 response to eliminate the pathogen. We produce plots of active disease progression, control and clearance for varying levels of Th1 effectiveness.


7461.      Marrie TJ, Carriere KC, Jin Y, Johnson DH.  Factors associated with death among adults <55 years of age hospitalized for community-acquired pneumonia.Clin Infect Dis. 2003 Feb 15;36(4):413-21.

An administrative database was used to study death occurring among adults aged 18-55 years who were hospitalized during the period from 1 April 2024 through 31 March 1999 for treatment of community-acquired pneumonia. In-hospital case-fatality rates for the first 10 days of hospitalization and overall were 2.1% and 3.2%, respectively, for 11,684 patient hospitalizations. Patient factors (age, sex, and comorbidity) were the most important associations with death. Aspiration provided the largest explanation of variance in deaths occurring during the first 10 days of hospitalization (odds ratio, 5.0; 95% confidence interval, 3.7-6.8). Busy hospitals (higher occupancy and higher number of daily admissions) were not associated with higher case-fatality rates. Bigger hospitals (metropolitan hospitals) had higher case-fatality rates, but this was more likely related to greater comorbidity and severity of pneumonia. Death due to community-acquired pneumonia among young and middle-aged adults is infrequent and is more related to the severity of pneumonia and to such risk factors as aspiration than to the manner in which the provision of care is organized.

7462.      Miller DM, Light D.  Laboratory and clinical comparisons of the Streamlined Liner of the Pharynx Airway (SLIPA) with the laryngeal mask airway. Anaesthesia. 2003 Feb;58(2):136-42.

The Streamlined Liner of the Pharynx Airway (SLIPA) is a new inexpensive disposable supraglottic airway designed to seal without the use of an inflatable cuff. It comprises a hollow blow-moulded soft plastic airway shaped to form a seal in the pharynx. Being hollow, liquid entrapment is possible and this may provide effective protection against aspiration. A model silicone rubber pharynx with an 'oesophageal' tube for injecting volumes of regurgitant liquid was designed to evaluate the SLIPA and the standard and ProSeal laryngeal mask airways during positive-pressure ventilation. A linear relationship between the volume 'regurgitated' and the volume 'aspirated' was found with the laryngeal mask airway and the ProSeal laryngeal mask airway with the drainage tube clamped. Both the ProSeal laryngeal mask airway with an open drainage tube and the SLIPA, but not the standard laryngeal mask airway, provided effective protection against 'aspiration' during positive-pressure ventilation using the model. In a clinical study, 120 patients were randomly allocated to receive controlled ventilation of the lungs via the standard laryngeal mask airway or the SLIPA. Both devices were equally easy to insert and satisfactory for airway management.


October 2003


  8108.      Balloy V, Sallenave JM, Crestani B, Dehoux M, Chignard M. Neutrophil DNA contributes to the antielastase barrier during acute lung inflammation. Am J Respir Cell Mol Biol. 2003 Jun;28(6):746-53. Epub 2003 Jan 10.


During acute lung inflammation, the airspaces are invaded by circulating neutrophils. These may then injure tissues through the release of elastase. Different natural specific inhibitors such as alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin are nonetheless able to counteract the enzymatic activity of elastase. The present study was undertaken to assess the role of these different inhibitors in the intrinsic antielastase barrier during lipopolysaccharide-induced lung inflammation in mice. Upon intranasal administration of lipopolysaccharide to mice, the antielastase activity recovered from bronchoalveolar lavage fluids (BALF) increases progressively up to 48 h (7-fold) and returns to the basal level within 72 h. By contrast, when the same experiments are performed with neutropenic mice (pretreatment with an antigranulocyte antibody, or vinblastine), the increase is almost totally absent. Ultrafiltration of BALF through 100 kD cutoff membranes shows that the activity remains in the retentate, thus ruling out a role for native alpha1-proteinase inhibitor, secretory leukocyte proteinase inhibitor, and elafin. Gel filtration and fraction analysis show that the material eluted with a Mr of 600 kD. Agarose gel electrophoresis and ethidium bromide staining reveal that the activity corresponds to the presence a large amount of DNA. Interestingly, DNase treatment of the active fraction suppresses the antielastase activity. Analysis of BALF from patients with acute lung inflammation shows the presence of DNA with antielastase activity. We therefore concluded that during acute lung inflammation, the recruitment of neutrophils in the airspaces accounts for the increased presence of DNA, which in turn contributes to the antielastase barrier.


8109.  Biernacki WA, Kharitonov SA, Barnes PJ.  Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD. Thorax. 2003 Apr;58(4):294-8.


BACKGROUND: Exacerbations are an important feature of chronic obstructive pulmonary disease (COPD), accounting for a large proportion of health care costs. They are associated with increased airway inflammation and oxidative stress. METHODS: Concentrations of leukotriene B4 (LTB4), a marker of inflammation, and 8-isoprostane, a marker of oxidative stress, were measured in the exhaled breath condensate of 21 patients (11 M) with COPD during an exacerbation and 2 weeks after treatment with antibiotics. In 12 patients who had no further exacerbations these markers were also measured after 2 months. RESULTS: LTB4 concentrations were raised during the COPD exacerbation (mean (SE) 15.8 (1.1) pg/ml and fell after treatment with antibiotics to 9.9 (0.9) pg/ml (p<0.0001). In 12 patients the level of LTB4 fell further from 10.6 (1.1) pg/ml to 8.5 (0.8) pg/ml (p<0.005) after 2 months. In 12 normal age matched subjects the LTB4 levels were 7.7 (0.5) pg/ml. Concentrations of 8-isoprostane were also increased during the exacerbation (13.0 (0.9) pg/ml) and fell after antibiotic treatment to 9.0 (0.6) pg/ml (p<0.0001). In 12 patients there was a further fall from 9.3 (0.7) pg/ml to 6.0 (0.7) pg/ml (p<0.001) after 2 months compared with normal subjects (6.2 (0.4) pg/ml). CONCLUSIONS: Non-invasive markers of inflammation and oxidative stress are increased during an infective exacerbation of COPD and only slowly recover after treatment with antibiotics.

8110.  Butler JC, Bosshardt SC, Phelan M, Moroney SM, Tondella ML, Farley MM, Schuchat A, Fields BS.  Classical and latent class analysis evaluation of sputum polymerase chain reaction and urine antigen testing for diagnosis of pneumococcal pneumonia in adults. J Infect Dis. 2003 May 1;187(9):1416-23. Epub 2003 Apr 09.


Diagnosis of pneumococcal pneumonia is complicated by the lack of a diagnostic reference standard that is highly sensitive and specific. Latent class analysis (LCA) is a mathematical technique that relates an unobserved ("latent") infection to multiple diagnostic test results by use of a statistical model. We used classical analysis and LCA to evaluate the sensitivity and specificity of blood culture, sputum Gram stain, sputum polymerase chain reaction (PCR), and urine antigen testing for diagnosing pneumococcal pneumonia among 149 adults with community-acquired pneumonia. On the basis of LCA models, sensitivity of autolysin PCR and pneumolysin PCR was 82% and 89%, respectively, but specificity was low, 38% and 27%, respectively. For urine antigen testing, sensitivity was 77%-78%, and specificity was 67%-71%. Results of the LCA models were comparable with those obtained from classical analysis. LCA may be useful for diagnostic test evaluation and for determining the prevalence of pneumococcal infection in epidemiological studies of community-acquired pneumonia and in vaccine efficacy trials.


8111.  Combes A, Figliolini C, Trouillet JL, Kassis N, Dombret MC, Wolff M, Gibert C, Chastre J.  Factors predicting ventilator-associated pneumonia recurrence. Crit Care Med. 2003 Apr;31(4):1102-7.


OBJECTIVE: To determine the factors associated with ventilator-associated pneumonia recurrence in patients alive after 8 days of treatment for a first episode. DESIGN: A 16-month, prospective, observational cohort study of patients diagnosed with a first ventilator-associated pneumonia episode. Predictors of recurrence were assessed by logistic regression analysis. SETTING: Two intensive care units in a university hospital. PATIENTS: Bronchoscopy was performed in 124 patients with clinically or radiologically suspected ventilator-associated pneumonia. Ventilator-associated pneumonia was confirmed by the presence of at least two of the following criteria: >/=2% of cells with intracellular bacteria found on direct examination of bronchoalveolar lavage fluid, protected specimen brush sample culture >/=103 colony-forming units/mL, or bronchoalveolar lavage culture >/=104 colony-forming units/mL. Ventilator-associated pneumonia recurrence was confirmed using the same microbiological criteria. Antibiotic treatment for ventilator-associated pneumonia lasted 14 days. MEASUREMENTS AND MAIN RESULTS: Clinical, radiologic, and biological data at intensive care unit admission, on the day of bronchoscopy (D1) and on D8, and outcome variables were prospectively recorded. Ventilator-associated pneumonia recurred in 28 patients (all of them still on mechanical ventilation on D8), 21 +/- 9 days after the first episode (82% after D14). Factors significantly associated with recurrence were: acute respiratory failure as initial reason for mechanical ventilation, D1 radiologic score >7, D8 radiologic score >8, adult respiratory distress syndrome on D8, mechanical ventilation persistence on D8, D8 temperature >38 degrees C, and D8 temperature >D1 temperature, but not disease-severity scores at inclusion and D8, or first-episode pathogen(s). Multivariate analysis identified D1 radiologic score >7 (odds ratio = 3.9; 95% confidence interval, 1.3-11.6), D8 temperature >38 degrees C (odds ratio = 4.4; 95% confidence interval, 1.4-13.4), and adult respiratory distress syndrome on D8 (odds ratio = 14.6; 95% confidence interval, 1.5-143.5) as predictors of recurrence. CONCLUSIONS: Factors of ventilator-associated pneumonia recurrence evaluated on D8 of a 14-day course of antibiotics are linked to the severity of lung injury and persistence of fever, but not to first-episode pathogen(s).

8112.  Helweg-Larsen J. S-adenosylmethionine in plasma to test for Pneumocystis carinii pneumonia. Lancet. 2003 Apr 12;361(9365):1237.  No abstract.

8113.  Hoth JJ, Burch PT, Bullock TK, Cheadle WG, Richardson JD. Pathogenesis of posttraumatic empyema: the impact of pneumonia on pleural space infections. Surg Infect (Larchmt). 2003 Spring;4(1):29-35.


BACKGROUND: Thoracic empyema may result either from primary pneumonic sources or intraabdominal sources of infection that seed the pleural space secondarily. In patients with thoracostomy tubes, empyema may result when blood in the pleural space becomes contaminated during tube insertion. To elucidate the cause of posttraumatic empyema, preoperative bronchoalveolar lavage (BAL)/sputum cultures obtained from patients with posttraumatic empyema were compared with cultures obtained at the time of decortication. MATERIALS AND METHODS: A retrospective study was conducted of trauma patients who developed empyema and underwent either video-assisted thoracoscopy or thoracotomy with decortication following blunt or penetrating trauma. At our level I trauma center, we studied all empyema cases diagnosed from November, 1998 to July, 2001. Data collection included patient demographics, injuries sustained, preoperative BAL/sputum cultures, and culture data obtained at the time of decortication. All BAL/sputum cultures were performed no more than 5 days prior to decortication. RESULTS: Thirty-seven patients (26 blunt/11 penetrating) were identified. No patients had concurrent intra-abdominal sources of infection. All patients had at least one chest tube placed prior to decortication. Preoperative respiratory cultures (BAL/sputum) were obtained in 34 patients. The most common organisms isolated were Staphylococcus aureus in six patients (18%) and Hemophilus influenzae in six patients (18%). Intraoperative cultures were obtained in all 37 patients, with the most common organism being S. aureus isolated in 22 patients (60%). Interestingly, a correlation between preoperative BAL/sputum and intraoperative cultures was found in only seven of the 34 patients (21%) who had concomitant respiratory and pleural cultures. Cultures positive for S. aureus were isolated from five patients, Streptococcus pneumoniae from one patient, and Pseudomonas aeruginosa from one patient. CONCLUSION: Little correlation existed between preoperative BAL/sputum cultures and intraoperative cultures in this series of patients with posttraumatic empyema. This suggests that the causation is most often not a parapneumonic process. Furthermore, since S. aureus was the most common organism recovered from empyema, the source was more likely from inoculation of the pleural space by the injury itself or by tube thoracostomy.

8114.  Pikus L, Levine MS, Yang YX, Rubesin SE, Katzka DA, Laufer I, Gefter WB.  Videofluoroscopic studies of swallowing dysfunction and the relative risk of pneumonia. AJR Am J Roentgenol. 2003 Jun;180(6):1613-6.


OBJECTIVE: The purpose of our investigation was to determine the relationship between the degree of swallowing dysfunction observed on barium studies and the likelihood of developing pneumonia in a large series of patients. MATERIALS AND METHODS: The findings on videofluoroscopic swallowing studies in 381 patients were used to classify these patients into one of five groups: those with normal swallowing; those with abnormal swallowing but no laryngeal penetration or tracheobronchial aspiration; those with laryngeal penetration; those with tracheobronchial aspiration; and those with silent tracheobronchial aspiration. Clinical data were also reviewed to determine how many patients had developed pneumonia during the 6 months before or after the barium studies. The data were then analyzed to determine whether the risk of developing pneumonia increased significantly with each level of swallowing dysfunction seen on barium studies. RESULTS: No significant difference was found in the frequency of pneumonia in patients with abnormal swallowing but no laryngeal penetration or tracheobronchial aspiration compared with patients with normal swallowing on barium studies (p = 0.85). In contrast, patients with laryngeal penetration, tracheobronchial aspiration, or silent tracheobronchial aspiration were approximately four times (p = 0.008), 10 times (p < 0.0001), and 13 times (p < 0.0001), respectively, more likely to develop pneumonia than those with normal swallowing. CONCLUSION: Our findings indicate that the likelihood of developing pneumonia is directly related to the degree of swallowing dysfunction seen on videofluoroscopic studies. Patients with no laryngeal penetration-regardless of whether they had normal or abnormal swallowing-have the lowest risk of developing pneumonia. Patients with laryngeal penetration, tracheobronchial aspiration, or silent tracheobronchial aspiration are, in increasing order of magnitude, significantly more likely to develop pneumonia than patients with normal swallowing.


8115.  Sharma R; Guleria R; Pande JN. Idiopathic pulmonary fibrosis: newer concepts and management strategies. Indian Journal of Chest Diseases and Allied Sciences 2003 Jan-Mar; 45(1): 31-49.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic fibrosing interstitial pneumonia limited to the lung and associated with the histologic appearance of usual interstitial pneumonia(UIP) on lung biopsy. It is characterized by progressive dyspnea, worsening of pulmonary function and radiographically, by patchy subpleural interstitial infiltrates with minimal ground glass appearance predominantly affecting the lung bases. The etiology is unknown and no therapy has been clearly shown to prolong survival. The diagnosis, which earlier was difficult to establish, is now based on guidelines of American Thoracic Society. Never insight into its etiopathogenesis, particularly the mechanisms involved including T helper 1 (Th1) and T helper 2 (Th2) types of responses occurring after the initial and repetitive lung insults and the ineffectiveness of conventional modes of therapy has prompted clinicians worldwide to look for alternative modes of therapy. Conventional therapy for this disorder has been steroids and immunosuppressive. Immunomodulators (Interferon gamma 1b) and antioxidants (Glutathione and its precursor N-acetyl cysteine) are promising results in this, otherwise, uniformly fatal condition.


8116.  Skelly M, Hoffman J, Fabbri M, Holzman RS, Clarkson AB Jr, Merali S. S-adenosylmethionine concentrations in diagnosis of Pneumocystis carinii pneumonia. Lancet. 2003 Apr 12;361(9365):1267-8.


Pneumocystis carinii is unable to synthesise S-adenosylmethionine and thus scavenges this intermediate. We aimed to test whether measurement of concentrations of this metabolic intermediate in plasma could provide a new method for rapid diagnosis of Pneumocystis carinii pneumonia (PCP). We measured S-adenosylmethionine plasma concentrations in 12 healthy controls, 16 patients with confirmed or suspected PCP, and 36 patients with other infections. Median concentration in healthy controls was 106 nmol/L (range 86-128), but the protein was undetectable in eight patients with histologically proven and seven with suspected PCP, and was 8 nmol/L in another confirmed case (p<0.0001). In 36 patients with other infections, S-adenosylmethionine concentrations were much the same as in controls: 18 had bacterial pneumonia, two tuberculosis, five cryptococcal meningitis, three had other infections, and eight had asymptomatic HIV-1 infection. After treatment for PCP, S-adenosylmethionine concentrations rose rapidly in all but one patient who died of the disease. Measurement of plasma S-adenosylmethionine concentrations could prove useful for diagnosis of PCP and assessment of patients' response to treatment.

8117.  Stewart GA, Hoyne GF, Ahmad SA, Jarman E, Wallace WA, Harrison DJ, Haslett C, Lamb JR, Howie SE.  Expression of the developmental Sonic hedgehog (Shh) signalling pathway is up-regulated in chronic lung fibrosis and the Shh receptor patched 1 is present in circulating T lymphocytes. J Pathol. 2003 Apr;199(4):488-95.


During pulmonary development, Sonic hedgehog (Shh) and transforming growth factor beta1 (TGF-beta1) signalling both contribute to branching morphogenesis. In interstitial lung disease, the complex alveolar structure of the lung is disrupted and remodelled, which leads to fibrosis, loss of respiratory surface, morbidity, and mortality. It is well documented that TGF-beta1 is involved in fibrosis. However, little is known about Shh signalling in damaged epithelia. This study examined whether or not components of the Shh signalling pathway, as well as TGF-beta1, are expressed in human fibrotic lung disease (cryptogenic fibrosing alveolitis and bronchiectasis) and in murine experimental models of fibrotic and non-fibrotic chronic pulmonary inflammation. Using immunohistochemistry, it was observed that Shh, like TGF-beta1, is up-regulated in epithelial cells at sites of fibrotic disease but not non-fibrotic inflammation. The Shh receptor patched was detected in infiltrating mononuclear cells and alveolar macrophages, as well as normal resting peripheral blood T lymphocytes. Neither Shh nor patched is expressed by hyperproliferative goblet cells in inflammatory epithelium. This study demonstrates that patched is present in human peripheral CD4 and CD8 lymphocytes at both protein and Mrna levels. Taken together, these results suggest that components of the highly conserved Shh signalling pathway may play a role in the remodelling of damaged pulmonary epithelium and that damaged epithelium and cells of the immune system may communicate via this pathway. Copyright 2003 John Wiley & Sons, Ltd.

8118.  Wacogne I, Negrine RJ. Are follow up chest x ray examinations helpful in the management of children recovering from pneumonia? Arch Dis Child. 2003 May;88(5):457-8. Review. No abstract.

8119.  Wahl WL, Franklin GA, Brandt MM, Sturm L, Ahrns KS, Hemmila MR, Arbabi S. Does bronchoalveolar lavage enhance our ability to treat ventilator-associated pneumonia in a trauma-burn intensive care unit? J Trauma. 2003 Apr;54(4):633-8; discussion 638-9.


BACKGROUND: Recent literature supports the notion that bronchoalveolar lavage (BAL) in ventilated trauma patients may improve our ability to diagnose and treat ventilator-associated pneumonia (VAP). We hypothesized that BAL would decrease the number of cases of VAP diagnosed and impact our antibiotic use and ventilator days. METHODS: Prospective data on all infectious complications were collected for patients admitted to the trauma-burn service for the year 2001. All VAPs between January 1, 2001, through June 30, 2001, were diagnosed without BAL (No BAL group) using clinical signs of fever, sputum production, leukocytosis, chest radiographs, and sputum culture. After July 1, 2001, VAP was diagnosed with the use of BAL. RESULTS: There were 37 cases of VAP in the No BAL group (11%) and 29 cases of VAP (8%) in the BAL group. There were no statistical differences in Injury Severity Score, hospital length of stay, ventilator days, or mortality between the two groups. The time to initial treatment of VAP was shorter for the BAL group, but did not reach significance. The number of patients who had their VAP pathogens correctly treated with empiric antibiotics was also the same between the two groups. There was no difference in the rate of recurrent pneumonias. The antibiotic costs and respiratory therapy/ventilator costs were not statistically different between the groups for trauma patients, although antibiotic costs were higher for burn patients. CONCLUSION: The routine use of BAL to diagnose VAP in our mixed trauma-burn population did not impact on clinical outcomes or antibiotic use. Our results do not justify the additional costs and potential risks of BAL for all patients. The means of VAP diagnosis may not be as important as choosing the appropriate antibiotics for common VAP organisms in any given intensive care unit.


8120.  Zampetaki A, Minamino T, Mitsialis SA, Kourembanas S. Effect of heme oxygenase-1 overexpression in two models of lung inflammation. Exp Biol Med (Maywood). 2003 May;228(5):442-6.


An increasing number of studies implicate heme oxygenase-1 (HO-1) in the regulation of inflammation. Although the mechanisms involved in this cytoprotection are largely unknown, HO-1 and its enzymatic products, carbon monoxide and bilirubin, downregulate the inflammatory response by either attenuating the expression of adhesion molecules and thus inhibiting leukocyte recruitment or by repressing the induction of cytokines and chemokines. In the present study we used genetically engineered mice that express high levels of a human cDNA HO-1 transgene in lung epithelium to assess the effect of HO-1 on lung inflammation. Two separate models of inflammation were studied: hypoxic exposure and lipopolysaccharide (LPS) challenge. We found that both mRNA and protein levels of specific cytokines and chemokines were significantly elevated in response to hypoxia in the lungs of wild-type mice after 2 and 5 days of exposure but significantly suppressed in the hypoxic lungs of transgenic mice, suggesting that inhibition of these cytokines was caused by overexpression of HO-1. However, LPS treatment resulted in a very pronounced increase in mRNA levels of several cytokines in both wild-type and transgenic mice. Despite the high mRNA levels, significantly lower cytokine protein levels were detected in the bronchoalveolar lavage of HO-1 overexpressing mice compared with wild type, indicating that HO-1 leads to repression of cytokines in the airway. These results demonstrate that HO-1 activity operates through distinct molecular mechanisms to confer cytoprotection in the hypoxic and the LPS models of inflammation.




8121.  Cagli S, Oktar N, Dalbasti T, Erensoy S, Ozdamar N, Goksel S, Sayiner A, Bilgic A. Failure to detect Chlamydia pneumoniae DNA in cerebral aneurysmal sac tissue with two different polymerase chain reaction methods. J Neurol Neurosurg Psychiatry. 2003 Jun;74(6):756-9. Review.


OBJECTIVE: Chlamydia pneumoniae (C pneumoniae) is a common cause of a usually mild, community acquired pneumonia. This organism, however, can spread from the respiratory tract into other parts of the body and has been detected in up to 70% of atheromatous lesions in blood vessels. Although the exact mechanism of the C Pneumoniae contribution to the pathogenesis of atherosclerosis remains unknown, prophylactic antibiotic trials are planned for people at high risk for coronary disease. METHOD: In this study the authors aimed to investigate C pneumoniae DNA content in the cerebral aneurysmal sac tissue with the aid of polymerase chain reaction (PCR) method. C pneumoniae DNA was searched in 15 surgically clipped and removed aneurysmal sac tissue and in two tumour (an ependymoma of the fourth ventricle and a craniofaringoma) samples by touchdown enzyme time release PCR (TETR PCR) targeting 16S rRNA gene and by nested PCR targeting ompA gene. RESULTS: Both PCR methods were sensitive to detect in C pneumoniae 4x10(-2) genomes. C pneumoniae DNA was not detected in any of the 17 sample tissues of these patients. CONCLUSION: The contribution of C pneumoniae in the development of intracranial aneurysms cannot be excluded despite the results of this study. Further studies on the possible role of C pneumoniae or any other micro-organisms in the pathogenesis of aneurysms should be performed.

8122.  Gao B, Flores SC, Leff JA, Bose SK, McCord JM. Synthesis and anti-inflammatory activity of a chimeric recombinant superoxide dismutase: SOD2/3. Am J Physiol Lung Cell Mol Physiol. 2003 Jun;284(6):L917-25. Epub 2003 Jan 10.


External surfaces of cells are normally protected by extracellular superoxide dismutase, SOD3, which binds to polyanions such as heparan sulfate. We constructed a fusion gene encoding a chimeric SOD consisting of the mature human mitochondrial SOD2 plus the COOH-terminal 26-amino acid heparin-binding "tail" from SOD3. This tail is responsible for the enzyme's affinity for endothelial surfaces. The fusion gene was expressed in Escherichia coli, and the fully active enzyme SOD2/3 was purified. Although native SOD2 has no affinity for heparin, SOD2/3 binds to a heparin-agarose column. In a rat model of acute lung injury induced by intratracheal instillation of IL-1, SOD2/3, SOD2, and denatured SOD2/3 showed 92%, 13.8%, and 0% reduction of lung leak, respectively. Only SOD2/3 prevented neutrophil accumulation. In the carrageenan-induced foot edema model in the rat, SOD2/3 reduced edema by 62% (P < 0.003) at a dose in which native SOD2 produced no significant effect. Thus SOD2/3 appears to have properties as a therapeutic anti-inflammatory agent that are greatly superior to other available forms of the enzyme.

8123.  Gow A, Ischiropoulos H. Super-SOD: superoxide dismutase chimera fights off inflammation. Am J Physiol Lung Cell Mol Physiol. 2003 Jun;284(6):L915-6. No abstract.

8124.  Kawayama T, Fujiki R, Honda J, Rikimaru T, Aizawa H. High concentration of (1-->3)-beta-D-glucan in BAL fluid in patients with acute eosinophilic pneumonia. Chest. 2003 Apr;123(4):1302-7.


Our aim in the study was to investigate the pathogenesis of eosinophilic inflammation in patients with acute eosinophilic pneumonia (AEP), and to determine the levels of (1-->3)-beta-D-glucan, which is one of the major components of the cell wall of most fungi, in the BAL fluid (BALF) of those patients with AEP. Six patients with AEP and five patients with chronic eosinophilic pneumonia (CEP) that was in the acute stage and had been newly diagnosed, and nine healthy subjects from the Kurume University School of Medicine and the Social Institute Tagawa Hospital between 1995 and 2001 were entered into the study. In AEP patients, (1-->3)-beta-D-glucan was detected in BALF, and these findings were compared with BALF findings in patients with CEP as well as with those in healthy subjects. In the BALF of AEP patients, the mean concentration of (1-->3)-beta-D-glucan was significantly higher (p < 0.05) than that of CEP patients as well as healthy subjects. In patients with AEP, the mean concentration of (1-->3)-beta-D-glucan in BALF was significantly higher (p < 0.05) than that in the blood. In four of six patients with AEP, we measured serial changes in (1-->3)-beta-D-glucan levels, and the level of (1-->3)-beta-D-glucan in the BALF decreased with clinical improvement at follow-up. We concluded that inhaled (1-->3)-beta-D-glucan may be involved in the mechanisms of pulmonary inflammation in patients with AEP.

8125.  Pikus L, Levine MS, Yang YX, Rubesin SE, Katzka DA, Laufer I, Gefter WB.  Videofluoroscopic studies of swallowing dysfunction and the relative risk of pneumonia. AJR Am J Roentgenol. 2003 Jun;180(6):1613-6.


OBJECTIVE: The purpose of our investigation was to determine the relationship between the degree of swallowing dysfunction observed on barium studies and the likelihood of developing pneumonia in a large series of patients. MATERIALS AND METHODS: The findings on videofluoroscopic swallowing studies in 381 patients were used to classify these patients into one of five groups: those with normal swallowing; those with abnormal swallowing but no laryngeal penetration or tracheobronchial aspiration; those with laryngeal penetration; those with tracheobronchial aspiration; and those with silent tracheobronchial aspiration. Clinical data were also reviewed to determine how many patients had developed pneumonia during the 6 months before or after the barium studies. The data were then analyzed to determine whether the risk of developing pneumonia increased significantly with each level of swallowing dysfunction seen on barium studies. RESULTS: No significant difference was found in the frequency of pneumonia in patients with abnormal swallowing but no laryngeal penetration or tracheobronchial aspiration compared with patients with normal swallowing on barium studies (p = 0.85). In contrast, patients with laryngeal penetration, tracheobronchial aspiration, or silent tracheobronchial aspiration were approximately four times (p = 0.008), 10 times (p < 0.0001), and 13 times (p < 0.0001), respectively, more likely to develop pneumonia than those with normal swallowing. CONCLUSION: Our findings indicate that the likelihood of developing pneumonia is directly related to the degree of swallowing dysfunction seen on videofluoroscopic studies. Patients with no laryngeal penetration-regardless of whether they had normal or abnormal swallowing-have the lowest risk of developing pneumonia. Patients with laryngeal penetration, tracheobronchial aspiration, or silent tracheobronchial aspiration are, in increasing order of magnitude, significantly more likely to develop pneumonia than patients with normal swallowing.

8126.  Ursi D, Ieven M, Noordhoek GT, Ritzler M, Zandleven H, Altwegg M. An interlaboratory comparison for the detection of Mycoplasma pneumoniae in respiratory samples by the polymerase chain reaction. J Microbiol Methods. 2003 Jun;53(3):289-94.


A panel of 78 respiratory samples collected from 43 patients was analyzed in three different Centers for the presence of Mycoplasma pneumoniae DNA by polymerase chain reaction (PCR). One Center collected the samples and extracted the DNA by two different methods. DNA extracted according to the first method was amplified using primers targetting the 16 S rRNA gene. DNA extracted according to the second method was amplified using the same primers in a semi-nested format and was sent to the two other Centers. The latter Centers both used the same primers targetting the P1 gene but with a different detection format. Thirty-nine samples (50%) from 19 patients were positive by at least two PCR assays. None of the laboratories were free of false positive or false negative PCR results. Calculated specificities of the individual PCR assays ranged from 97.4% to 87.2% and sensitivities ranged from 97.4% to 89.2%. Complement fixation was done on sera of 33 patients. The calculated specificity and sensitivity of serology was 100% and 58.8%, respectively. Several aspects concerning false positive and false negative results with PCR are discussed.

8127.  Zhou H, Cheng X, Jin H.  Identification of amino acids that are critical to the processivity function of respiratory syncytial virus M2-1 protein. J Virol. 2003 May;77(9):5046-53.


The M2-1 protein of respiratory syncytial virus (RSV) is a transcription processivity factor that is essential for virus replication. The function of RSV M2-1 protein can be examined by using an RSVlacZ minigenome assay in vitro since the expression of the lacZ gene is dependent on M2-1. The M2-1 protein of pneumonia virus of mice (PVM), also a member of the Pneumovirus genus, functions poorly in the RSVlacZ minigenome assay despite conservation of the Cys(3)-His(1) motif at its N terminus and an overall 40% amino acid identity with RSV M2-1. To identify the amino acids responsible for the differences between these two proteins, two chimeric proteins were constructed. The RSV/PVM (RP) M2-1 chimera that contains the N-terminal 30 amino acids from RSV and the remaining C-terminal 148 amino acids from PVM maintained a level of activity at an ca. 36% of RSV M2-1. However, the PVM/RSV (PR) M2-1 chimera with the N-terminal 29 amino acids from PVM and 164 amino acids from RSV had an activity of <5% of RSV M2-1, indicating that the functional determinants are mainly located in the N terminus of M2-1. Mutagenesis of the N terminus of PR M2-1 and RSV M2-1 identified that Leu-16 and Asn-17 of RSV M2-1 are critical to the M2-1 function. In addition, several charged residues in the N terminus of RSV M2-1 also contributed to the functional integrity of M2-1.


8128.  Jakobsen H, Sigurdsson VD, Sigurdardottir S, Schulz D, Jonsdottir I.  Pneumococcal serotype 19F conjugate vaccine induces cross-protective immunity to serotype 19A in a murine pneumococcal pneumonia model. Infect Immun. 2003 May;71(5):2956-9.


Immunization with a pneumococcal conjugate vaccine (PNC) containing serotype 19F induces cross-reactive antibodies to 19A in mice and human infants. Active immunization with PNC and passive immunization with serum samples from infants vaccinated with PNC containing serotype 19F, but not serotype 19A, protected against lung infection caused by both serotypes in a murine model.

8129.  Merrill JD, Ballard RA. Pulmonary surfactant for neonatal respiratory disorders. Curr Opin Pediatr. 2003 Apr;15(2):149-54.


Surfactant therapy has revolutionized neonatal care and is used routinely for preterm infants with respiratory distress syndrome. Recent investigation has further elucidated the function of surfactant-associated proteins and their contribution toward surfactant and lung immune defense functions. As the field of neonatology moves away from intubation and mechanical ventilation of preterm infants at birth toward more aggressive use of nasal continuous positive airway pressure, the optimal timing of exogenous surfactant therapy remains unclear. Evidence suggests that preterm neonates with bronchopulmonary dysplasia and prolonged mechanical ventilation also experience surfactant dysfunction; however, exogenous surfactant therapy beyond the first week of life has not been well studied. Surfactant replacement therapy has been studied for use in other respiratory disorders, including meconium aspiration syndrome and pneumonia. Commercial surfactant preparations currently available are not optimal, given the variability of surfactant protein content and their susceptibility to inhibition. Further progress in the treatment of neonatal respiratory disorders may include the development of "designer" surfactant preparations.


8130.  Sato N, Tagami H. Severe measles in a young female patient with chronic, generalized Trichophyton rubrum infection showing type 2 helper T cell-dominant immunologic reactivity. J Am Acad Dermatol. 2003 May;48(5 Suppl):S43-6.


An obese 18-year-old girl without a history of atopic dermatitis or a systemic immunosuppressive disorder had severe measles with liver dysfunction and pneumonia. For the previous 3 years she had had a chronic untreated generalized Trichophyton rubrum infection. The rash of the measles tended to spare the fungal lesions, where numerous fungi grew in the stratum corneum. Serum IgE level was markedly elevated (>16,000 IU/mL) and decreased after effective antifungal therapy. Delayed skin hypersensitivity reactions to trichophytin and tuberculin were negative, but the immediate skin hypersensitivity to trichophytin was positive. These data indicate that the patient had acquired hyperproduction of IgE with suppression of cell-mediated immunity, that is, acquired impairment of the balance between type 1 and type 2 helper T cells. In this case, chronic T rubrum infection was thought to have a role in driving a normal balance between type 1 and type 2 helper T cells toward type 2 helper T cell-dominant immunity. The result was deterioration of the measles infection and prolongation of the dermatophytosis.


8131.  Wislez M, Massiani MA, Milleron B, Souidi A, Carette MF, Antoine M, Cadranel J. Clinical characteristics of pneumonic-type adenocarcinoma of the lung. Chest. 2003 Jun;123(6):1868-77.


PURPOSE: To analyze diagnostic approaches, survival predictors, and treatment efficacy in pneumonic-type adenocarcinoma (P-ADC). PATIENTS AND METHODS: Fifty-two patients with P-ADC diagnosed between January 1986 and December 2000 were studied. P-ADC was defined as histologically or cytologically proven pulmonary adenocarcinoma with a pneumonia-like consolidation, in a patient with no prior diagnosis of thoracic or extrathoracic adenocarcinoma. RESULTS: Sixty percent of the patients were men (n = 31), and 65% (n = 34) were current or former smokers. Mean (+/- SD) age at diagnosis was 66 +/- 1.4 years. P-ADC was diagnosed by routine chest radiography in 17% of cases (n = 9). Bronchorrhea was present in 31% of cases (n = 16), and crepitant rales in 58% (n = 30). The primary tumor appeared as consolidations, which could not be assessed and were thus classified Tx, in 83% of the patients (n = 43). Ten percent of the patients

(n = 5) had a satellite tumor within the lobe containing the primary tumor (T4), and 63% (n = 33) had a satellite tumor in another lobe (M1). Extrathoracic metastases were present in 5% of cases (n = 3). Bronchial biopsy, transbronchial biopsy, bronchial aspiration, and BAL were positive in 21%, 80%, 44%, and 66% of cases, respectively. The median survival time after diagnosis was 10.5 months (range, 1 to 150 months). The outcome of patients treated by lobectomy or bilobectomy was significantly better than that of patients treated with pneumonectomy, chemotherapy, or best supportive care (p < 0.01). Bronchorrhea and crepitant rales were independent predictors of shorter survival when the treatment modality (surgery vs no surgery) was not entered as a risk factor. CONCLUSIONS: P-ADC is characterized by aerogenous propagation, as emphasized by the results of multivariate analysis showing that bronchorrhea and crepitant rales were the only two independent factors of shorter survival. Surgery remains the most effective treatment in P-ADC, especially when lobectomy is feasible. As CT is not sensitive enough to detect multifocal lesions, new tools are required to evaluate pulmonary involvement and thereby to refine the surgical strategy.




Back to reference