DIARRHOEA

(Diagnosis, Diagnostics, Immunodiagnosis, Immunodiagnostics, Pathogenesis, Vaccines & Drugs)

ABSTRACTS

1217. Bardsley-Elliot A. Plosker GL. Nelfinavir: an update on its use in HIV infection. [Review] [198 refs] Drugs. 59(3):581-620, 2000 Mar.

Abstract

Nelfinavir is one of several currently available protease inhibitors used to limit viral replication and improve immune function in HIV-infected individuals. It is administered in combination with other antiretroviral agents. Nelfinavir has been evaluated as first-line therapy with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-naïve patients, or as an additional antiretroviral agent in protease inhibitor-naive patients already receiving NRTIs. These studies have shown good efficacy in terms of HIV viral load reduction and increased CD4+ cell counts. When used in combination with NRTIs, nelfinavir 1250 mg twice daily produced similar results to 750 mg 3 times daily. The more convenient twice-daily dosage schedule, which is now approved in the US, may be beneficial in improving patient adherence to therapy. Nelfinavir has also been used successfully in combination with non-nucleoside reverse transcriptase inhibitors and/or other protease inhibitors, with or without NRTIs. Resistance to nelfinavir has been observed in vitro and in clinical isolates from patients experiencing insufficient or waning viral suppression during treatment. Nelfinavir primarily selects for the D30N mutation, which is not seen with other protease inhibitors, and alone does not cause resistance to other protease inhibitors in vitro. Several studies have shown that patients who experience virological failure while receiving nelfinavir can respond to salvage therapy with other protease inhibitors. Diarrhoea is the most frequent adverse event in patients receiving nelfinavir-based combination therapy, but was generally mild and resulted in minimal discontinuation of therapy in clinical trials. Diarrhoea can usually be controlled with drugs that slow gastrointestinal motility. Metabolic disturbances associated with protease inhibitor use (hypercholesterolaemia, hyperglycaemia and lipodystrophy) have also been reported with nelfinavir. Nelfinavir is associated with a number of clinically significant drug interactions and coadministration of some drugs (e.g. astemizole, cisapride, triazolam) is contraindicated. Coadministration of nelfinavir with other protease inhibitors generally resulted in favourable pharmacokinetic interactions (usually increased area under the concentration-time curve for both drugs). Conclusion: Nelfinavir, in combination with reverse transcriptase inhibitors and/or other protease inhibitors, is effective in limiting HIV replication and increasing CD4+ cell counts in HIV-infected adults and children. The convenience of its dosage administration, the low incidence of adverse events, and the potential for salvage therapies indicate that nelfinavir

(as part of combined antiretroviral therapy regimens) should be considered as a first-line option in protease inhibitor-naive patients and in those unable to tolerate other protease inhibitors. [References: 198]

1218. Green DA. Murphy WG. Uttley WS. Haemolytic uraemic syndrome: prognostic factors [see comments]. Clinical & Laboratory Haematology. 22(1):11-4, 2000 Feb.

Abstract

Haemolytic uraemic syndrome (HUS) associated with Escherichia coli O157:H7 is the commonest cause of acute renal failure (ARF) in childhood. Production of verotoxin by the organism is pivotal in the pathogenesis of the disease. Verotoxin binds to a receptor on blood and endothelial cells, expressed as the P1 blood group antigen on red blood cells. A protective effect of the P1 phenotype has been proposed in this disease. This study investigates prognostic factors and the relationship between outcome and P1 phenotype in 27 cases of diarrhoea-associated HUS. A poor outcome as defined by the presence of chronic renal failure (CRF), hypertension or proteinuria on 6 month follow-up was associated with the age of the patient at presentation and with the following clinical markers: maximum WBC and duration of raised WBC, duration of anuria and duration of need for dialysis. None of these outcome measures or prognostic factors, and no extra-renal manifestations of the disease were associated with P1 phenotype.

1219. Khare MD. Sharland M. Pulmonary manifestations of pediatric HIV infection. [Review] [26 refs] Indian Journal of Pediatrics. 66(6):895-904, 1999 Nov-Dec.

Abstract

Vertically acquired HIV infection is becoming increasingly common in India. The main clinical manifestations of HIV in childhood are growth failure, lymphadenopathy, chronic cough and fever, recurrent pulmonary infections, and persistent diarrhoea. Pulmonary disease is the major cause of morbidity and mortality in pediatric AIDS, manifesting itself in more than 80% of cases. The most common causes are Pneumocystis carinii pneumonia (PCP), lymphocytic interstitial pneumonitis (LIP), recurrent bacterial infections which include bacterial pneumonia and tuberculosis. The commonest AIDS diagnosis in infancy is PCP, presenting in infancy with tachypnea, hypoxia, and bilateral opacification on chest-X-ray (CXR). Treatment is with cotrimoxazole. LIP presents with bilateral reticulonodular shadows on CXR. It may be asymptomatic in the earlier stages, but children develop recurrent bacterial super infections, and can progress to bronchiectasis. LIP is a good prognostic sign in children with HIV infection in comparison to PCP. HIV should be considered in children with recurrent bacterial pneumonia, particularly with a prolonged or atypical course, or a recurrence after standard treatment. Pulmonary TB is common in children with HIV, but little data is available to guide treatment decisions. Much can be done to prevent PCP and bacterial infections with cotrimoxazole prophylaxis and appropriate immunisations, which may reduce hospital admissions and health care costs. [References: 26]

1220. Kothari S. Prabhakar G. Kalra VB. Colorectal carcinoma. Indian Journal of Pediatrics. 65(6):913-6, 1998 Nov-Dec.

Abstract

Two rare cases of colorectal adenocarcinoma seen during the last 3 years in children under 10 years of age are reported. To improve survival, emphasis is given on its early diagnosis by a thorough examination and investigation of the child in every case of prolonged bleeding per rectum, diarrhoea and other non specific abdominal symptoms.

1221. Kumar A. St John MA. HIV infection among children in Barbados. West Indian Medical Journal. 49(1):43-6, 2000 Mar.

Abstract

We studied a cohort of children with the human immunodeficiency virus (HIV) infection in Barbados in order to determine the prevalence of HIV infection, the clinical course including morbidity and mortality and the magnitude of the health care and social problems. Forty-seven children were diagnosed with HIV infection during the study period. The number of HIV infected children increased from 5 during 1981-85, to 14 during 1986-90, and to 21 during the 1991-95 period. The majority (91.5%) of infections resulted from perinatal transmission. Six (12.8%) cases remained asymptomatic and 41 (87.2%) were symptomatic with 19(46.3%) presenting in infancy, while 22 (53.5%) presented post-infancy. The median age at diagnosis (class P-2) was 13 months. Generalized lymphadenopathy (47.5%), hepatosplenomegaly (40.0%), failure to thrive (27.5%), persistent recurrent diarrhoea (15.0%), oral candidiasis (37.5%), Pneumocystis carinii pneumonia (37.5%), lymphoid interstitial pneumonia (12.5%) and progressive neurological disease (10.0%) were common HIV related conditions. Two children developed non-hodgkin's lymphoma. The median age at death for 23 children was 12 months, whereas the median survival after diagnosis was 4 months. Mortality was higher among those diagnosed in infancy (73.7%) as compared to those diagnosed post-infancy (42.8%). Pneumocystis carinii pneumonia was the most common (65.2%) cause of death. Paediatric HIV infection is rising and contributes considerably to infant mortality. In this study, children took longer to be symptomatic when compared to other reports. However, once symptomatic, they died early.

1222. Plosker GL. Foster RH. Tacrolimus: a further update of its pharmacology and therapeutic use in the management of organ transplantation. Drugs. 59(2):323-89, 2000 Feb.

Abstract

Tacrolimus (FK-506) is an immunosuppressant agent that acts by a variety of different mechanisms which include inhibition of calcineurin. It is used as a therapeutic alternative to cyclosporin, and therefore represents a cornerstone of immunosuppressive therapy in organ transplant recipients. Tacrolimus is now well established for primary immunosuppression in liver and kidney transplantation, and experience with its use in other types of solid organ transplantation, including heart, lung, pancreas and intestinal, as well as its use for the prevention of graft-versus-host disease in allogeneic bone marrow transplantation (BMT), is rapidly accumulating. Large randomised nonblind multicentre studies conducted in the US and Europe in both liver and kidney transplantation showed similar patient and graft survival rates between treatment groups (although rates were numerically higher with tacrolimus- versus cyclosporin-based immunosuppression in adults with liver transplants), and a consistent statistically significant advantage for tacrolimus with respect to acute rejection rate. Chronic rejection rates were also significantly lower with

tacrolimus in a large randomised liver transplantation trial, and a trend towards a lower rate of chronic rejection was noted with tacrolimus in a large multicentre renal transplantation study. In general, a similar trend in overall efficacy has been demonstrated in a number of additional clinical trials comparing tacrolimus- with cyclosporin-based immunosuppression in various types of transplantation. One notable exception is in BMT, where a large randomised trial showed significantly better 2-year patient survival with cyclosporin over tacrolimus, which was primarily attributed to patients with advanced haematological malignancies at the time of (matched sibling donor) BMT. These survival results in BMT require further elucidation. Tacrolimus has also demonstrated efficacy in various types of transplantation as rescue therapy in patients who experience persistent acute rejection (or significant adverse effect's) with cyclosporin-based therapy, whereas cyclosporin has not demonstrated a similar capacity to reverse refractory acute rejection. A corticosteroid-sparing effect has been demonstrated in several studies with tacrolimus, which may be a particularly useful consideration in children receiving transplants. The differences in the tolerability profiles of tacrolimus and cyclosporin may well be an influential factor in selecting the optimal treatment for patients undergoing organ transplantation. Although both drugs have a similar degree of nephrotoxicity, cyclosporin has a higher incidence of significant hypertension, hypercholesterolaemia, hirsutism and gingival hyperplasia, while tacrolimus has a higher incidence of diabetes mellitus, some types of neurotoxicity (e.g. tremor, paraesthesia), diarrhoea and alopecia. Conclusion: Tacrolimus is an important therapeutic option for the optimal individualisation of immunosuppressive therapy in transplant recipients.

1223. No Abstract

1224. Soliman AT. elZalabany MM. Bappal B. alSalmi I. de Silva V. Asfour M.

Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth. Indian Journal of Pediatrics. 66(3):363-73, 1999 May-Jun.

Abstract

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood

and an autosomal recessive mode of transmission.

1225. Xenos ES. Halverson JD. Duodenocolic fistula: case report and review of the literature. Journal of Postgraduate Medicine. 45(3):87-9, 1999 Jul-Sep.

Abstract

Duodenocolic fistula is a rare complication of malignant and inflammatory bowel disease. It presents as diarrhoea and faeculent vomiting. The diagnosis is established with upper and lower gastrointestinal tract contrast studies. A case is reported and the optimal operative procedure is discussed.

1631. Baqai R. Rapid diagnosis of rotavirus in infantile diarrhoea [letter]. JPMA - Journal of the Pakistan Medical Association. 50(7):243-4, 2000 Jul.

1632. Ford HE. Cunningham D. Ross PJ. Rao S. Aherne GW. Benepal TS. Price T. Massey A. Vernillet L. Gruia G. Phase I study of irinotecan and raltitrexed in patients with advanced gastrointestinal tract adenocarcinoma. British Journal of Cancer. 83(2):146-52, 2000 Jul.

Abstract

To determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of irinotecan and raltitrexed given as sequential short infusions every 3 weeks, 33 patients with pretreated gastrointestinal adenocarcinoma (31 colorectal, 2 oesophagogastric) entered this open label dose-escalation study. For the first five dose levels patients received irinotecan 175-350 mg m(-2) followed by raltitrexed 2.6 mg m(-2). Level VI was irinotecan 350 mg m(-2) plus raltitrexed 3.0 mg m(-2), level VII was irinotecan 400 mg m(-2) plus raltitrexed 2.6 mg m(-2); 261 courses were administered. Only one patient at dose levels I-V experienced DLT. At level VI, 5/12 patients experienced DLT: one had grade 3 diarrhoea and lethargy, one had grade 4 diarrhoea and one had lethargy alone. Two others had lethargy caused by disease progression. There was no first-cycle neutropenia. At level VII, 3/6 patients experienced dose-limiting lethargy, one also had grade 3 diarrhoea. Dose intensity fell from over 90% for both drugs at level VI to 83% for irinotecan and 66% for raltitrexed at level VII. Lethargy was therefore the DLT, and level VII the MTD. Pharmacokinetic data showed no measurable drug interaction; 6/30 patients (20%) had objective responses. This combination is active with manageable toxicity. Recommended doses for further evaluation are irinotecan 350 mg m(-2) and raltitrexed 3.0 mg m(-2).

1633. Freyer G. Rougier P. Bugat R. Droz JP. Marty M. Bleiberg H. Mignard D. Awad L. Herait P. Culine S. Trillet-Lenoir V. Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure. CPT-11 F205, F220, F221 and V222 study groups. British Journal of Cancer. 83(4):431-7, 2000 Aug.

Abstract

Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias, data from those studies could be pooled for statistical analysis. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea at first cycle and a low number of organs involved were the most PF for tumour growth control (P<0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA value (P < or =0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P< or =0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single agent and in combination with other drugs.

1634. Gordon JN. An unusual cause of watery diarrhoea. Diagnosis: metastatic Zollinger-Ellison syndrome. Postgraduate Medical Journal. 76(898):512, 517-8, 2000 Aug.

1635. Kaakkola S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. [Review] [109 refs] Drugs. 59(6):1233-50, 2000 Jun.

Abstract

When peripheral decarboxylation is blocked by carbidopa or benserazide, the main metabolic pathway of levodopa is O-methylation by catechol-O-methyltransferase (COMT). Entacapone and tolcapone are new potent, selective and reversible nitrocatechol-type COMT inhibitors. Animal studies have demonstrated that entacapone mainly has a peripheral effect whereas tolcapone also inhibits O-methylation in the brain. In human volunteers, both entacapone and tolcapone dose-dependently inhibit the COMT activity in erythrocytes, improve the bioavailability and decrease the elimination of levodopa, and inhibit the formation of 3-O-methyldopa (3-OMD). Entacapone is administered with every scheduled dose of levodopa whereas tolcapone is administered 3 times daily. The different administration regimens for these agents are based on their different pharmacokinetic and pharmacodynamic profiles. Both entacapone and tolcapone enhance and extend the therapeutic effect of levodopa in patients with advanced and fluctuating Parkinson's disease. They prolong the duration of levodopa effect. Clinical studies show that they increase the daily ON time by an average 1 to 3 hours, improve the activities of daily living and allow daily levodopa dosage to be decreased. Correspondingly, they significantly reduce the daily OFF time. No comparative studies between entacapone and tolcapone have been performed. Tolcapone also appears to have a beneficial effect in patients with nonfluctuating Parkinson's disease. The main adverse effects of the COMT inhibitors are related to their dopaminergic and gastrointestinal effects. Enhancement of dopaminergic activity may cause an initial worsening of levodopa-induced adverse effects, such as dyskinesia, nausea, vomiting, orthostatic hypotension, sleep disorders and hallucinations. Levodopa dose adjustment is recommended to avoid these events. Tolcapone is associated with diarrhoea in about 16 to 18% of patients and entacapone in less than 10% of patients. Diarrhoea has led to discontinuation in 5 to 6% of patients treated with tolcapone and in 2.5% of those treated with entacapone. Urine discoloration to dark yellow or orange is related to the colour of COMT inhibitors and their metabolites. Elevated liver transaminase levels are reported in 1 to 3% of patients treated with tolcapone but very rarely, if at all, in patients treated with entacapone. The descriptions of acute, fatal fulminant hepatitis and potentially fatal neurological reactions, such as neuroleptic malignant syndrome and rhabdomyolysis, in association with tolcapone led to the suspension of its marketing authorisation in the European Community and Canada. In many other countries, the use of tolcapone is restricted to patients who are not responding satisfactorily to other therapies. Regular monitoring of liver enzymes is required if tolcapone is used. No such adverse reactions have so far been described for entacapone and no laboratory monitoring has been proposed. COMT inhibitors added to levodopa therapy are beneficial, particularly in patients with fluctuating disease. They may be combined with other antiparkinsonian drugs, such as dopamine agonists, selegiline and anticholinergics without adverse interactions. They provide a new treatment possibility in patients with Parkinson's disease who have problems with their present levodopa therapy. [References: 109]

1636. Minke WE. Pickens J. Merritt EA. Fan E. Verlinde CL. Hol WG. Structure of m-carboxyphenyl-alpha-D-galactopyranoside complexed to heat-labile enterotoxin at 1.3 A resolution: surprising variations in ligand-binding modes. Acta Crystallographica Section D-Biological Crystallography. 56 ( Pt 7):795-804, 2000 Jul.

Abstract

In the quest to develop drugs against traveller's diarrhoea and cholera, the structure of the B pentamer of heat-labile enterotoxin (LT) complexed with a new receptor-binding antagonist, m-carboxyphenyl-alpha-D-galactopyranoside, has been determined. The high resolution obtained for this structure allowed anisotropic refinement of the model. It was also now possible to confirm at a near-atomic resolution the structural similarity between the B subunits of LT and the closely related cholera toxin (CT), including the similarity in deviations of Planarity of the same peptide unit in LT and CT. The structure of the LT complex clearly revealed different conformations for the m--carboxyphenyl moiety of the ligand in the five B subunits of LT, while the binding modes of the well defined galactopyranoside moieties were identical. In two binding sites the m-carboxyphenyl moiety displayed no significant electron density, demonstrating significant flexibility of this moiety. In a third binding site the m-carboxyphenyl moiety could be modelled unambiguously into the density. The two remaining binding sites were involved in crystal packing contacts and the density for the ligands in these two binding sites clearly revealed different binding modes, of which one conformation was identical to and one completely different from the conformation of m-carboxyphenyl-galactopyranoside in the third subunit. The multiple binding modes observed in the crystal may represent the ensemble of conformations of m-carboxyphenyl-alpha-D-galactopyranoside complexed to LT in solution.

1637. Morton SJ. Powell RJ. Cyclosporin and tacrolimus: their use in a routine clinical setting for scleroderma. Rheumatology (Oxford). 39(8):865-9, 2000 Aug.

Abstract

BACKGROUND: Cyclosporin and tacrolimus are immunomodulatory drugs which act predominantly on T cells. Improvements in certain manifestations, particularly skin tightness, have been observed in a number of patients with scleroderma treated with these drugs. However, to date there have been no reports of their use in a routine clinical setting. METHODS: Patients attending clinical immunology clinics who had progressive systemic sclerosis and related syndromes and who had received cyclosporin and/or tacrolimus were identified. Details of their treatment, including drug dosage, duration of and response to treatment, side-effects and reasons for withdrawal, were recorded. RESULTS: Sixteen patients had been given cyclosporin and 13 of these had been treated for skin tightness. Half noticed significant softening of their skin whilst on treatment, and resolution was observed in all four of the patients treated for digital vasculitis. Side-effects were common and dose-limiting, and contributed to withdrawal in 12 out of 13 patients. Eight patients had been treated with tacrolimus; two of these had stopped the drug because of progression of their disease, one developed diarrhoea, prompting withdrawal, one stopped tacrolimus following improvement, and four remained on the drug. Side-effects had occurred in three patients. CONCLUSION: Improvements in skin occur in approximately half of all cases of scleroderma treated with either cyclosporin or tacrolimus, suggesting a beneficial effect. Side-effects, especially hypertension, are common with cyclosporin and often necessitate withdrawal. Adverse effects are also observed with tacrolimus, but in the small cohort so far treated only one patient had stopped the drug for this reason.

1638. Oberg K. State of the art and future prospects in the management of neuroendocrine tumors. [Review] [87 refs] Quarterly Journal of Nuclear Medicine. 44(1):3-12, 2000 Mar.

Abstract

Neuroendocrine gastroenteropancreatic tumors are rather rare neoplasms with an incidence of 1-2 cases per 100,000 people. They show rather varying tumor biology and present sometimes distinct clinical symptoms such as flushing, diarrhoea, hypoglycemia and gastric ulcers. The biochemical diagnosis is today significantly improved by the introduction of chromogranin A as a general tumor marker, which is also useful in histopathology. Today the localization procedures include somatostatin receptor scintigraphy as the primary investigation together with CT or ultrasonography. The basis for treatment of neuroendocrine GEP tumors is not only a curative intent but merely amelioration of clinical symptoms, abrogation of tumor growth, maintaining and improvement of quality of life. Surgery has always to be considered in the treatment of neuroendocrine GEP tumors. It can be performed whenever during the course of the disease but it may be more productive in earlier stages. Liver dearterialization procedures can furthermore reduce the tumor masses in liver together with laser treatment or radiofrequency therapy. The medical treatment includes cytotoxic agents, alpha interferons and somatostatin analogues. Somatostatin analogues will always be combined with the other two alternatives to reduce clinical symptoms. Chemotherapy is particularly useful for patients with more aggressive tumors with high proliferation capacity, whereas alpha interferon is beneficial in classical midgut carcinoids with low proliferation capacity. Quite recently somatostatin based radioactive tumor targeted treatment has evolved with preliminary promising data but further studies are needed to deliniate its future role in the treatment of neuroendocrine tumors in patients. [References: 87]

1639. Oed C. Rosenburg R. Loew-Friedrich I. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology (Oxford). 39(6):655-65, 2000 Jun.

Abstract

OBJECTIVE: To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). METHODS: In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. RESULTS: After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate vs no drug-related deaths among the subjects receiving leflunomide. CONCLUSIONS: Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.

1640. Storey PA. Faile G. Hewitt E. Yelifari L. Polderman AM. Magnussen P. Clinical epidemiology and classification of human oesophagostomiasis. Transactions of the Royal Society of Tropical Medicine & Hygiene. 94(2):177-82, 2000 Mar-Apr.

Abstract

The intestinal helminth Oesophagostomum bifurcum is highly and focally endemic in northern Ghana and Togo, and its juveniles produce a nodular inflammatory response as they develop in the intestinal wall. This pathology can produce clinical symptoms. We report on 156 cases of oesophagostomiasis presenting in 1996-98 to Nalerigu hospital in northern Ghana. The disease accounted for 0.2% of the out-patient department new presentations (about 1 patient per week), and 1% (16) of the major acute surgical cases. Children aged 5-9 years were most commonly affected. Multinodular disease (13% of the cases) results from hundreds of pea-sized nodules within the colon wall and other intra-abdominal structures, and presents with general abdominal pain, persistent diarrhoea and weight loss. Dapaong tumour (87%) presents as an abdominal inflammatory mass often associated with fever. The 3-6-cm tumour is painful, well-delineated, smooth, spherical, 'wooden', periumbilical, and adhered to the abdominal wall. Cases most commonly presented during the late rains and early dry season. Diagnosis by ultrasound has reduced the need for exploratory surgery, and the ability to sonographically evaluate conservative treatment with albendazole has curtailed management by colectomy or incision and drainage.

1641. Sultana Q. Chaudhry NA. Munir M. Anwar MS. Tayyab M. Diagnosis of Clostridium difficile antibiotic associated diarrhoea culture versus toxin assay. JPMA - Journal of the Pakistan Medical Association. 50(8):246-9, 2000 Aug.

Abstract

OBJECTIVE: To compare the results of Clostridium Difficile (CD) on culture with detection of C. difficile toxin by Enzyme Immunoassay (EIA) in the stool specimens of hospitalized patients with antibiotic associated diarrhoea (AAD). PATIENTS AND METHODS: The study included 80 adult patients with AAD and 20 adult patients with non-AAD. Stool specimens of all these subjects were inoculated on cycloserine cefoxitin fructose agar and incubated anaerobically to isolate C. difficile. At the same time, all the stool specimens were tested for C. difficile toxin by EIA technique using cytoclone A and B kit manufactured by Cambridge Biotech Corporation, Worcester, Massachusette. RESULTS: Out of 80 adult patients with AAD, thirty were females and fifty males. C. difficile was isolated on culture from stool specimen of 16 patients, while twenty-three stool specimens were positive for C. difficile toxin. From 20 control subjects, C. difficile was isolated from stool specimen of only one subject. No stool specimen from the controls was positive for toxin. CONCLUSION: Diagnosis of CDAAD by culture is difficult and time consuming because of strict anaerobic nature of organism. Moreover, mere isolation of C. difficile on culture is not sufficient to establish the pathogenic role of these isolates. C. difficile toxin detection by EIA technique is a highly sensitive and specific method for diagnosis of CDAAD. Using this method, results are available in three hours time. Therefore, EIA is recommended for rapid diagnosis of CDAAD.

1631. Baqai R. Rapid diagnosis of rotavirus in infantile diarrhoea [letter]. JPMA - Journal of the Pakistan Medical Association. 50(7):243-4, 2000 Jul.

Abstract

1634. Gordon JN. An unusual cause of watery diarrhoea. Diagnosis: metastatic Zollinger-Ellison syndrome. Postgraduate Medical Journal. 76(898):512, 517-8, 2000 Aug.

1635. Kaakkola S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. [Review] [109 refs] Drugs. 59(6):1233-50, 2000 Jun.

Abstract

1637. Morton SJ. Powell RJ. Cyclosporin and tacrolimus: their use in a routine clinical setting for scleroderma. Rheumatology (Oxford). 39(8):865-9, 2000 Aug.

Abstract

1638. Oberg K. State of the art and future prospects in the management of neuroendocrine tumors. [Review] [87 refs] Quarterly Journal of Nuclear Medicine. 44(1):3-12, 2000 Mar.

Abstract

Abstract

2129. Abdelgabar A. Owen A. Starczewski A. Subashchandran R. A case of voluminous diarrhoea with hypokalaemic acidosis. International Journal of Clinical Practice. 55(1):64-5, 2001 Jan-Feb.

Abstract

We describe a patient presenting with voluminous diarrhoea, hypokalaemic acidosis and hypercalcaemia who was found to have a vasoactive intestinal polypeptide-producing tumour. His diarrhoea was initially mild and intermittent requiring no medical attention. We report on two children, a 12-year-old boy and a 6-year-old girl, with simultaneous occurrence of clinical and laboratory features consistent with both diarrhoea-negative haemolytic uraemic syndrome (D-HUS) and acute post-infectious glomerulonephritis (APGN). Both presented with acute renal insufficiency, hypertension and oedema. Laboratory evaluation revealed micro-angiopathic anaemia with burr cells, thrombocytopenia, elevated lactic dehydrogenase and low complement C3. Urinalysis showed marked proteinuria and haematuria. Renal biopsy was characteristic of APGN, but not of HUS. The outcome was good in both children. Conclusion. The simultaneous occurrence of diarrhoea-negative haemolytic uraemic syndrome and acute post-infectious glomerulonephritis is rare. The outcome is generally good as is expected in the latter condition in contrast to the former. [References: 15]

2138. Bytzer P. Talley NJ. Jones MP. Horowitz M. Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus. Alimentary Pharmacology & Therapeutics. 15(1):137-42, 2001 Jan.

Abstract

BACKGROUND: Gastrointestinal symptoms are commonly reported as side-effects of oral hypoglycaemic drugs. It may be very difficult to distinguish between spontaneous and truly drug-related symptoms due to the high background incidence of gastrointestinal symptoms. Gastrointestinal symptoms in diabetic patients have also been linked to factors associated with long-standing disease and suboptimal control. AIM: To explore the association between gastrointestinal symptoms and treatment with oral hypoglycaemic drugs in a large cohort of subjects with type 2 diabetes. PATIENTS AND METHODS: 956 subjects with type 2 diabetes participated in the study. All subjects completed a validated, self-administered questionnaire on gastrointestinal symptoms, diabetes, drug use and various potential risk factors for gastrointestinal symptoms. The association between oral hypoglycaemics and nine gastrointestinal symptom groups was assessed based on logistic regression. RESULTS: 405 of the 956 patients used oral hypoglycaemic drugs. Metformin use was independently associated with chronic diarrhoea (odds ratio 3.08, 95% CI: 1.29-7.36, P < 0.02) and with faecal incontinence (odds ratio 1.95, 95% CI: 1.10-3.47, P < 0.05). Use of sulphonylureas was associated with less abdominal pain, but not with any other gastrointestinal symptom. CONCLUSIONS: Troublesome gastrointestinal symptoms do not appear to be caused by oral hypoglycaemics, except for diarrhoea and faecal incontinence, which are strongly and independently associated with metformin use.

2679. Al-Qurashi AR. El-Morsy F. Al-Quorain AA. Evolution of metronidazole and tetracycline susceptibility pattern in Helicobacter pylori at a hospital in Saudi Arabia. International Journal of Antimicrobial Agents. 17(3):233-6, 2001 Mar.

2680. Anonymous. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-2001. A 17-year-old girl with worsening abdominal pain, fever, and diarrhea after a recent cesarean section. New England Journal of Medicine. 344(21):1622-7, 2001 May 24.

2681. Asaeda G. The transport of ciguatoxin: a case report. Journal of Emergency Medicine. 20(3):263-5, 2001 Apr.

2682. Atmar RL. Estes MK. Diagnosis of noncultivatable gastroenteritis viruses, the human caliciviruses. [Review] [257 refs] Clinical Microbiology Reviews. 14(1):15-37, 2001 Jan.

2683. Bregeon F. Ciais V. Carret V. Gregoire R. Saux P. Gainnier M. Thirion X. Drancourt M. Auffray JP. Papazian L. Is ventilator-associated pneumonia an independent risk factor for death? [see comments]. Anesthesiology. 94(4):554-60, 2001 Apr.

2684. Buhimschi C. Weiner CP. Endotoxemia causing fetal bradycardia during urosepsis. Obstetrics & Gynecology. 97(5 Pt 2):818-20, 2001 May.

2685. Canducci F. Ojetti V. Pola P. Gasbarrini G. Gasbarrini A. Rifabutin-based Helicobacter pylori eradication 'rescue therapy'. Alimentary Pharmacology & Therapeutics. 15(1):143, 2001 Jan.

2686. Clarkson A. Ingleby E. Choonara I. Bryan P. Arlett P. A novel scheme for the reporting of adverse drug reactions. Archives of Disease in Childhood. 84(4):337-9, 2001 Apr.

2687. Cunha BA. Nosocomial pneumonia. Diagnostic and therapeutic considerations. [Review] [167 refs] Medical Clinics of North America. 85(1):79-114, 2001 Jan.

2688. D'Agata EM. Wise S. Stewart A. Lefkowitz LB Jr. Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site. Infection Control & Hospital Epidemiology. 22(1):10-2, 2001 Jan.

2689. Davidson JR. Rothbaum BO. van der Kolk BA. Sikes CR. Farfel GM. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Archives of General Psychiatry. 58(5):485-92, 2001 May.

2690. Drudy D. O'Donoghue DP. Baird A. Fenelon L. O'Farrelly C. Flow cytometric analysis of Clostridium difficile adherence to human intestinal epithelial cells. Journal of Medical Microbiology. 50(6):526-34, 2001 Jun.

2691. Formoso G. Maestri E. Magrini N. Koch M. Capurso L. Liberati A. Eradicating Helicobacter pylori in non-ulcer dyspepsia may not be cost effective. BMJ. 322(7285):557, 2001 Mar 3.

2692. Friedl W. Caspari R. Sengteller M. Uhlhaas S. Lamberti C. Jungck M. Kadmon M. Wolf M. Fahnenstich J. Gebert J. Moslein G. Mangold E. Propping P. Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. Gut. 48(4):515-21, 2001 Apr.

2693. Hancock EW. Postoperative tachycardia with possibly absent P waves. Hospital Practice (Office Edition). 36(5):11-2, 2001 May 15.

2694. Hassall E. Peptic ulcer disease and current approaches to Helicobacter pylori. Journal of Pediatrics. 138(4):462-8, 2001 Apr.

2695. Ho K. Bacteriophage therapy for bacterial infections. Rekindling a memory from the pre-antibiotics era. Perspectives in Biology & Medicine. 44(1):1-16, 2001 Winter.

2696. Ivandic A. Bozic D. Dmitrovic B. Vcev A. Canecki S. Gastropathy and diarrhea in diabetic patients: the presence of helicobacteriosis and PAS-positive vascular deposits in gastric and duodenal mucosa. Wiener Klinische Wochenschrift. 113(5-6):199-203, 2001 Mar 15.

2697. Jertborn M. Ahren C. Svennerholm AM. Dose-dependent circulating immunoglobulin A antibody-secreting cell and serum antibody responses in Swedish volunteers to an oral inactivated enterotoxigenic Escherichia coli vaccine. Clinical & Diagnostic Laboratory Immunology. 8(2):424-8, 2001 Mar.

2698. Laine L. Schoenfeld P. Fennerty MB. Therapy for Helicobacter pylori in patients with nonulcer dyspepsia. A meta-analysis of randomized, controlled trials. Annals of Internal Medicine. 134(5):361-9, 2001 Mar 6.

2699. Lee CK. Vaccination against Helicobacter pylori in non-human primate models and humans. [Review] [26 refs] Scandinavian Journal of Immunology. 53(5):437-42, 2001 May.

2700. Levtchenko EN. Ham HR. Levy J. Piepsz A. Attitude of Belgian pediatricians toward strategy in acute pyelonephritis. Pediatric Nephrology. 16(2):113-5, 2001 Feb.

2701. Mawhorter SD. Lauer MA. Is atherosclerosis an infectious disease?. [Review] [72 refs] Cleveland Clinic Journal of Medicine. 68(5):449-58, 2001 May.

2702. Morgner A. Bayerdorffer E. Neubauer A. Stolte M. Helicobacter pylori associated gastric B cell MALT lymphoma: predictive factors for regression. [letter; comment]. Gut. 48(3):290-2, 2001 Mar.

2703. Muller H. Volkholz H. Stolte M. Healing of lymphocytic gastritis by eradication of Helicobacter pylori. Digestion. 63(1):14-9, 2001.

2704. Mutlu GM. Mutlu EA. Factor P. GI complications in patients receiving mechanical ventilation. [see comments]. [Review] [225 refs] Chest. 119(4):1222-41, 2001 Apr.

2705. Nouri M. Terada H. Alfonso EC. Foster CS. Durand ML. Dohlman CH. Endophthalmitis after keratoprosthesis: incidence, bacterial causes, and risk factors. Archives of Ophthalmology. 119(4):484-9, 2001 Apr.

2706. Obuobie K. Ogunko A. Lazarus JH. Paralysis after a diarrhoeal illness. Journal of the Royal Society of Medicine. 94(5):241-2, 2001 May.

2707. O'Connor LA. De Guzman J. Emphysematous cystitis: a radiographic diagnosis. American Journal of Emergency Medicine. 19(3):211-3, 2001 May.

2708. Osato MS. Reddy SG. Piergies AA. Bochenek WJ. Testa RT. Graham DY. Comparative efficacy of new investigational agents against Helicobacter pylori. Alimentary Pharmacology & Therapeutics. 15(4):487-92, 2001 Apr.

2709. Pallister C. Rotstein OD. Yersinia enterocolitica as a cause of intra-abdominal abscess: the role of iron. Canadian Journal of Surgery. 44(2):135-6, 2001 Apr.

2710. Perna NT. Plunkett G 3rd. Burland V. Mau B. Glasner JD. Rose DJ. Mayhew GF. Evans PS. Gregor J. Kirkpatrick HA. Posfai G. Hackett J. Klink S. Boutin A. Shao Y. Miller L. Grotbeck EJ. Davis NW. Lim A. Dimalanta ET. Potamousis KD. Apodaca J. Anantharaman TS. Lin J. Yen G. Schwartz DC. Welch RA. Blattner FR. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. [see comments]. Nature. 409(6819):529-33, 2001 Jan 25.

2711. Potts JM. The four categories of prostatitis: a practical approach to treatment. Cleveland Clinic Journal of Medicine. 68(5):389-90, 392-3, 397, 2001 May.

2712. Pryor JP. Piotrowski E. Seltzer CW. Gracias VH. Early diagnosis of retroperitoneal necrotizing fasciitis. Critical Care Medicine. 29(5):1071-3, 2001 May.

2713. Robert PY. Adenis JP. Comparative review of topical ophthalmic antibacterial preparations. [Review] [65 refs] Drugs. 61(2):175-85, 2001.

2714. Robinson P. Okhuysen PC. Chappell CL. Lewis DE. Shahab I. Janecki A. White AC Jr. Expression of tumor necrosis factor alpha and interleukin 1 beta in jejuna of volunteers after experimental challenge with Cryptosporidium parvum correlates with exposure but not with symptoms. Infection & Immunity. 69(2):1172-4, 2001 Feb.

2715. Schilling JD. Mulvey MA. Hultgren SJ. Structure and function of Escherichia coli type 1 pili: new insight into the pathogenesis of urinary tract infections. [Review] [25 refs] Journal of Infectious Diseases. 183 Suppl 1:S36-40, 2001 Mar 1.

2716. Sher L. Effects of seasonal mood changes on seasonal variations in coronary heart disease: role of immune system, infection, and inflammation. Medical Hypotheses. 56(1):104-6, 2001 Jan.

2717. Sobrero A. Guglielmi A. Cirillo M. Recaldin E. Frassineti GL. Aschele C. Ravaioli A. Testore P. Caroti C. Gallo L. Pessi MA. Cortesi E. Turci D. Grossi F. Labianca R. 5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer. British Journal of Cancer. 84(8):1023-8, 2001 Apr 20.

2718. Stephenson J. Researchers describe latest strategies to combat antibiotic-resistant microbes. JAMA. 285(18):2317-8, 2001 May 9.

2719. Tan HH. Goh CL. Yeo MG. Tan ML. Antibiotic sensitivity of Propionibacterium acnes isolates from patients with acne vulgaris in a tertiary dermatological referral centre in Singapore. Annals of the Academy of Medicine, Singapore. 30(1):22-5, 2001 Jan.

2720. Valencia IC. Falabella A. Kirsner RS. Eaglstein WH. Chronic venous insufficiency and venous leg ulceration. [Review] [237 refs] Journal of the American Academy of Dermatology. 44(3):401-21; quiz 422-4, 2001 Mar.

2721. van der Voort PH. van der Hulst RW. Zandstra DF. van der Ende A. Kesecioglu J. Geraedts AA. Tytgat GN. Gut decontamination of critically ill patients reduces Helicobacter pylori acquisition by intensive care nurses. Journal of Hospital Infection. 47(1):41-5, 2001 Jan.

2722. Wagner PL. Acheson DW. Waldor MK. Human neutrophils and their products induce Shiga toxin production by enterohemorrhagic Escherichia coli. Infection & Immunity. 69(3):1934-7, 2001 Mar.

2723. Zhang HM. Ou ZL. Gondaira F. Ohmura M. Kojio S. Yamamoto T. Protective effect of anisodamine against Shiga toxin-1: inhibition of cytokine production and increase in the survival of mice. Journal of Laboratory & Clinical Medicine. 137(2):93-100, 2001 Feb.

Back To Reference