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Biomedical subjects

W A Khan

Publications and source records attributed to W A Khan.

At least 19 recordsLinked to original sources

Binding characteristics of SLE anti-DNA autoantibodies to Catecholestrogen-modified DNA.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which anti-double-stranded DNA antibody is a classic autoantibody that characterizes SLE. A role for oestrogens in the pathogenesis of SLE has been suspected for many years but the exact patho-aetiology remains elusive. In this study, the binding of SLE autoantibodies with native and 4-OHE(2)-NO-modified plasmid DNA were assessed. Binding specificity of antibodies was analysed by direct binding and inhibition enzyme-linked immunosorbent assay, quantitative precipitin titration and gel retardation assay. Anti-DNA IgG from SLE sera, purified on Protein A-Agarose matrix, exhibited increased recognition of 4-OHE(2)-NO-DNA than native DNA (P < 0.001). Gel retardation assay further substantiated the enhanced recognition of modified DNA by anti-DNA autoantibodies. The affinity of anti-DNA antibodies for modified polymer was found to be high as calculated by using Langmuir plot. DNA modified by 4-OHE(2)-NO presents unique neo-epitopes that might be one of the factor in antigen-driven induction of SLE autoantibodies.

Antibodies, Antinuclear↗

Risk factors for mortality due to shigellosis: a case-control study among severely-malnourished children in Bangladesh.

To determine the risk factors for death of severely-malnourished Bangladeshi children with shigellosis, a case-control study was conducted at the Clinical Research and Service Centre of ICDDR,B: Centre for Health and Population Research in Dhaka, Bangladesh. One hundred severely-malnourished children (weight-for-age <60% of median of the National Center for Health Statistics), with a positive stool culture for Shigella dysenteriae type 1 or S. flexneri, who died during hospitalization, were compared with another 100 similar children (weight-for-age <60% and with S. dysenteriae type 1 or S. flexneri-associated infection) discharged alive. Children aged less than four years were admitted during December 1993-January 1999. The median age of the cases who died or recovered was 9 months and 12 months respectively. Bronchopneumonia, abdominal distension, absent or sluggish bowel sound, clinical anaemia, altered consciousness, hypothermia, clinical sepsis, low or imperceptible pulse, dehydration, hypoglycaemia, high creatinine, and hyperkalaemia were all significantly more frequent in cases than in controls. In multivariate regression analysis, altered consciousness (odds ratio [OR]=2.6, 95% confidence interval [CI] 1.0-6.8), hypoglycaemia (blood glucose <3 mmol/L (OR=7.8, 95% CI 2.9-19.6), hypothermia (temperature <36 degrees C) (OR=5.7, 95% CI 1.5-22.1), and bronchopneumonia (OR=2.5, 95% CI 1.1-5.5) were identified as significant risk factors for mortality. Severely-malnourished children with shigellosis having hypoglycaemia, hypothermia, altered consciousness and/or bronchopneumonia were at high risk of death. Based on the findings, the study recommends that early diagnosis of shigellosis in severely-malnourished children and assertive therapy for proper management to prevent development of hypothermia, hypoglycaemia, bronchopneumonia, or altered consciousness and its immediate treatment are likely to reduce Shigella-related mortality in severely-malnourished children.

Bangladesh↗

Efficacy and tolerability of racecadotril in the treatment of cholera in adults: a double blind, randomised, controlled clinical trial.

BACKGROUND: The enkephalins, endogenous opiate substances, act as neurotransmitters along the entire digestive tract where they elicit intestinal antisecretory activity without affecting intestinal transit time or motility. Racecadotril, through inhibition of enkephalinase, reinforces the physiological activity of endogenous enkephalins and, therefore, shows intestinal antisecretory activity. AIM: We conducted the study to determine the role of racecadotril as an adjunct to the standard treatment of cholera in adults. METHODS: The study was a double blind, randomised, placebo controlled clinical trial involving 110 adult male cholera patients who received either racecadotril or placebo in addition to standard cholera treatment. The major outcome measures (stool output, oral rehydration solution (ORS) intake, requirements for unscheduled intravenous fluid infusion, and duration of diarrhoea) were compared between the groups. RESULTS: Of 110 patients enrolled, 54 received racecadotril and 56 received placebo. Admission clinical characteristics were comparable between the groups. There was no significant difference in (mean (SD)) total stool output (racecadotril v placebo 315 (228) v 280 (156) g/kg), total ORS intake (390 (264) v 369 (240) ml/kg), or duration of diarrhoea (35 (15) v 32 (13) hours) between the groups. Clinical success, defined as resolution of diarrhoea within 72 hours of initiation of study intervention, was similar in both groups (racecadotril v placebo 96% v 89%). The number of patients receiving unscheduled intravenous infusions was not significantly different between the groups (racecadotril v placebo 22% v 14%). No drug related adverse effect was noted. CONCLUSION: The study demonstrated that racecadotril therapy, although found to be safe, does not provide additional benefit in the treatment of severe cholera in adults.

Acute Disease↗

Effects of daily dermal application of DEET and epermethrin, alone and in combination, on sensorimotor performance, blood-brain barrier, and blood-testis barrier in rats.

DEET and permethrin were implicated in the development of illnesses in some veterans of the Persian Gulf War. This study was designed to investigate the effects of daily dermal application of these chemicals, alone or in combination, on the permeability of the blood-brain barrier (BBB) and blood-testes barrier (BTB) and on sensorimotor performance in male Sprague-Dawley rats. Groups of five rats were treated with a dermal daily dose of 4, 40, or 400 mg/kg DEET in ethanol or 0.013, 0.13, or 1.3 mg/kg permethrin in ethanol for 60 d. A group of 10 rats received a daily dermal dose of ethanol and served as controls. BBB permeability was assessed by injection of an iv dose of the quaternary ammonium compound [3H]hexamethonium iodide. While permethrin produced no effect on BBB permeability, DEET alone caused a decrease in BBB permeability in brainstem. A combination of DEET and permethrin significantly decreased the BBB permeability in the cortex. BTB permeability was decreased by treatment with DEET alone and in combination with permethrin. The same animals underwent a battery of functional behavior tests 30, 45, and 60 d after exposure to evaluate their sensorimotor abilities. All treatments caused a significant decline in sensorimotor performance in a dose- and time-dependent manner. These results show that daily dermal exposure to DEET, alone or in combination with permethrin, decreased BBB permeability in certain brain regions, and impaired sensorimotor performance.

Administration, Topical↗

Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination.

Since their return from Persian Gulf War (PGW), many veterans have complained of symptoms including muscle and joint pain, ataxia, chronic fatigue, headache, and difficulty with concentration. The causes of the symptoms remain unknown. Because these veterans were exposed to a combination of chemicals including pyridostigmine bromide (PB), DEET, and permethrin, we investigated the effects of these agents, alone and in combination, on the sensorimotor behavior and central cholinergic system of rats. Male Sprague-Dawley rats (200-250 gm) were treated with DEET (40 mg/kg, dermal) or permethrin (0.13 mg/kg, dermal), alone and in combination with PB (1.3 mg/kg, oral, last 15 days only), for 45 days. Sensorimotor ability was assessed by a battery of behavioral tests that included beam-walk score, beam-walk time, incline plane performance, and forepaw grip on days 30 and 45 following the treatment. On day 45 the animals were sacrificed, and plasma and CNS cholinesterase, and brain choline acetyl transferase, muscarinic and nicotinic acetylcholine receptors were evaluated. Animals treated with PB, alone or in combination with DEET and permethrin, showed a significant deficit in beam-walk score as well as beam-walk time as compared with controls. Treatment with either DEET or permethrin, alone or in combination with each other, did not have a significant effect on beam-walk score. All chemicals, alone or in combination, resulted in a significant impairment in incline plane testing on days 30 and 45 following treatment. Treatment with PB, DEET, or permethrin alone did not have any inhibitory effect on plasma or brain cholinesterase activities, except that PB alone caused moderate inhibition in midbrain acetylcholinesterase (AChE) activity. Treatment with permethrin alone caused significant increase in cortical and cerebellar AChE activity. A combination of DEET and permethrin or PB and DEET led to significant decrease in AChE activity in brainstem and midbrain and brainstem, respectively. A significant decrease in brainstem AChE activity was observed following combined exposure to PB and permethrin. Coexposure with PB, DEET, and permethrin resulted in significant inhibition in AChE in brainstem and midbrain. No effect was observed on choline acetyl transferase activity in brainstem or cortex, except combined exposure to PB, DEET, and permethrin caused a slight but significant increase in cortical choline acetyltransferase activity. Treatment with PB, DEET, and permethrin alone caused a significant increase in ligand binding for m2 muscarinic acetylcholine receptor (mAChR) in the cortex. Coexposure to PB, DEET, and permethrin did not have any effect over that of PB-induced increase in ligand binding. There was no significant change in ligand binding for nicotinic acetylcholine receptor (nAChR) associated with treatment with the chemical alone; a combination of PB and DEET or coexposure with PB, DEET, and permethrin caused a significant increase in nAChR ligand binding in the cortex. Thus, these results suggest that exposure to physiologically relevant doses of PB, DEET, and permethrin, alone or in combination, leads to neurobehavioral deficits and region-specific alterations in AChE and acetylcholine receptors.

Acetylcholinesterase↗

Hepatosplenic gamma/delta T-cell lymphoma in immunocompromised patients. Report of two cases and review of literature.

We describe 2 male patients in whom hepatosplenic gamma/delta T-cell lymphoma (HSTL) developed 6 and 10 years after renal transplantation. The onset was abrupt with systemic symptoms, cytopenia, and hepatosplenomegaly. The histologic examination of the spleen (case 1), liver, and bone marrow revealed sinusoidal infiltrates of markedly abnormal lymphocytes. The neoplastic cells in these cases were CD2+, CD3+, CD4-, CD5-, CD7+, CD8+, CD16+, CD56+, beta F1-negative, and TIA-1-negative. Both cases displayed clonal rearrangement of the T-cell receptor (TCR) delta gene and the TCR beta gene. The spleen in case 1 was positive for Epstein-Barr virus genome and showed TCR-gamma gene rearrangement by polymerase chain reaction. Isochromosome 7 [i(7)(q10)] was found in each case. Both patients died within 4 months of diagnosis. HSTL has been reported in only 5 renal transplant recipients. HSTL may be relatively more frequent in immunocompromised patients compared with the general population.

Adult↗

Cytodiagnosis of a meningeal fibrosarcoma metastatic to the thyroid gland.

A case of primary leptomeningeal fibrosarcoma metastatic to the thyroid gland, diagnosed by fine needle aspiration biopsy is described. The patient, a 39-year-old women was initially diagnosed with a leptomeningeal fibrosarcoma. Sections of the primary tumor studied by electron microscopy showed that the tumor cells have the ultrastructure features of a fibroblast. She underwent tumor resection, followed by chemotherapy and local radiotherapy. Four months later, she presented with dysphagia. Ultrasonography confirmed the presence of a 2-cm mass in the right lobe of thyroid. A fine needle aspiration biopsy was performed. Light microscopy showed interwoven bundles of neoplastic spindle cells similar to the primary tumor, consistent with a metastatic fibrosarcoma. To our knowledge, this is the first report of a primary meningeal fibrosarcoma that metastasized to the thyroid gland, which was diagnosed by a fine needle aspiration biopsy.

Adult↗

Subchronic effects following a single sarin exposure on blood-brain and blood-testes barrier permeability, acetylcholinesterase, and acetylcholine receptors in the central nervous system of rat: a dose-response study.

Subchronic neurotoxic effects of sarin (O-isopropyl methylphosphonofluoridate) treatment at various doses in male Sprague Dawley rats were studied. The animals were treated with a single intramuscular (im) injection of 0.01, 0.1, 0.5, or 1 x LD50 (100 microg/kg). The animals were maintained for 90 d thereafter. [3H]Hexamethonium iodide was used to monitor the changes in blood-brain barrier (BBB) permeability in cortex, brainstem, midbrain, and cerebellum. Brainstem exhibited a significant decrease (approximately 58% of control) in uptake of [3H]hexamethonium iodide at 1 x LD50 dose. No significant changes were observed in BBB permeability in cortex, midbrain, and cerebellum at any dose. Plasma butyrylcholinesterase (BChE) activity remained unchanged, reflecting recovery of the enzyme activity from the initial inhibition following single exposure of 1 x LD50 sarin. Acetylcholinesterase (AChE) activity in the cortex remained inhibited (approximately 29%), whereas in the brainstem there was an increase (approximately 20%) at 1 x LD50 dose of sarin. The m2-selective muscarinic acetylcholine receptor (m2-mAChR) ligand binding was inhibited significantly at 1 x LD50 in the cortex, whereas brainstem showed significantly increased (approximately 45%) ligand binding at 1 x LD50 dose. Nicotinic acetylcholine receptor (nAChR), on the other hand, showed a biphasic response in ligand binding in the cortex with a decrease (approximately 30%) at 0.01 x LD50 but an increase (approximately 40%) at 1 x LD5O. Brainstem did not show any significant change in nAChR ligand binding. These results suggest that single exposure of sarin could lead to changes that may play an important role in neuropathological abnormalities in the central nervous system.

Acetylcholinesterase↗

Acute sarin exposure causes differential regulation of choline acetyltransferase, acetylcholinesterase, and acetylcholine receptors in the central nervous system of the rat.

Acute neurotoxic effects of sarin (O:-isopropylmethylphosphonoflouridate) in male Sprague-Dawley rats were studied. The animals were treated with intramuscular (im) injections of either 1 x LD(50) (100 microg/kg), and sacrificed at 0. 5, 1, 3, 6, 15, or 20 h after treatment, or with im injections of either 0.01, 0.1, 0.5, or 1 x LD(50) and sacrificed 15 h after treatment. Plasma butyrylcholinesterase (BChE) and brain regional acetylcholinesterase (AChE) were inhibited (45-55%) by 30 min after the LD(50) dose. BChE in the plasma and AChE in cortex, brainstem, midbrain, and cerebellum remained inhibited for up to 20 h following a single LD(50) treatment. No inhibition in plasma BChE activity was observed 20 h after treatment with doses lower than the LD(50) dose. Midbrain and brainstem seem to be most responsive to sarin treatment at lower doses, as these regions exhibited inhibition (approximately 49% and 10%, respectively) in AChE activity following 0.1 x LD(50) treatment, after 20 h. Choline acetyltransferase (ChAT) activity was increased in cortex, brainstem, and midbrain 6 h after LD(50) treatment, and the elevated enzyme activity persisted up to 20 h after treatment. Cortex ChAT activity was significantly increased following a 0.1 x LD(50) dose, whereas brainstem and midbrain did not show any effect at lower doses. Treatment with an LD(50) dose caused a biphasic response in cortical nicotinic acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (m2-mAChR) ligand binding, using [(3)H]cytisine and [(3)H]AFDX-384 as ligands for nAChR and mAChR, respectively. Decreases at 1 and 3 h and consistent increases at 6, 15, and 20 h in nAChR and m2-mAChR were observed following a single LD(50) dose. The increase in nAChR ligand binding densities was much more pronounced than in mAChR. These results suggest that a single exposure of sarin, ranging from 0.1 to 1 x LD(50), modulates the cholinergic pathways differently and thereby causes dysregulation in excitatory neurotransmission.

Acetylcholinesterase↗

Central nervous system manifestations of childhood shigellosis: prevalence, risk factors, and outcome.

BACKGROUND AND OBJECTIVE: Alterations in consciousness, including seizures, delirium, and coma, are known to occur during Shigella infection. Previous reports have suggested that febrile convulsions and altered consciousness are more common during shigellosis than with other childhood infections. Those reports, however, have been from locations where S dysenteriae type 1 was not common, thus making it difficult to assess the specific contribution that S dysenteriae type 1 infection, and Shiga toxin, might make to the pathogenesis of altered consciousness in children with shigellosis. In this study we seek to determine the prevalence, risk factors, and outcome of altered consciousness in children with shigellosis in Bangladesh, a country where infection with all four species of Shigella is common. We particularly focus on the importance of metabolic abnormalities, which we have previously shown to be a common feature of shigellosis in this population. METHODS: This study was conducted at the Diarrhea Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh in Dhaka, Bangladesh, which provides care free of charge to persons with diarrhea. During 1 year, a study physician identified all inpatients infected with Shigella by checking the logs of the Clinical Microbiology Laboratory daily. Study physicians obtained demographic and historical information by reviewing the patient charts and by interviewing patients, or their parents or guardians, to confirm or complete the history of illness obtained on admission. Patients were categorized as being conscious or unconscious based on a clinical scale; having a seizure documented in the hospital; or having a seizure by history during the current illness that was not witnessed by medical personnel. Patient outcome was classified as discharged improved, discharged against medical advice, transferred to another health facility, or died in the Treatment Centre. Laboratory examinations were ordered at the discretion of the attending physician; all such information was recorded on the study form. Clinical management was by the attending physician. Factors independently predictive of a documented seizure, or of unconsciousness, were determined using a multiple logistic regression analysis. For this analysis variables associated with unconsciousness or a documented seizure in the analysis of variance or chi2 analyses were entered into the regression equation and eliminated in a backward stepwise fashion if the probability associated with the likelihood ratio statistic exceeded .10. RESULTS: During this 1-year study, 83 402 persons with diarrhea came to the Treatment Centre for care, and 6290 patients were admitted to the inpatient unit. Shigella was isolated from a stool or rectal swab sample of 863 (13.7%) of the inpatients. Seventy-one (8%) of the inpatients with shigellosis were >/=15 years old; 61 (86%) were conscious; 10 (14%) were unconscious; none had either a documented seizure or a seizure by history during this illness. Seven hundred ninety-two patients were <15 years old (92%); 654 (83%) were conscious; 73 (9%) were unconscious; 41 (5%) had a documented seizure (compared with >/=15-year age group); 24 (3%) had a seizure by history during this illness. Of the 41 patients with documented seizures, 19 (46.3%) had a seizure at the time of admission, and 22 (53.7%) had a seizure after admission. Twenty-five (61.0%) of the 41 patients with documented seizures were reported to have a seizure during this illness before coming to the Treatment Centre. Clinical features that are known to cause altered consciousness-fever, severe dehydration, hypoglycemia, hyponatremia, or meningitis-were present in 38 (92.7%) of the 41 patients in whom a seizure was witnessed and in 67 (91.8%) of the 73 patients who were unconscious. Nineteen (46. 3%) of the patients who had a seizure documented had two of these five features, 4 (9.8%) had three, and 1 (2. (ABSTRACT TRUNCATED)

Adolescent↗

Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis.

BACKGROUND: Infections caused by multiply resistant Shigella species are a major cause of childhood morbidity and mortality in Third World countries. The fluoroquinolone agent ciprofloxacin is active in vitro against these strains of bacteria, but has not been routinely used to treat acute childhood infections because of concern that quinolones may cause arthropathy in children. We undertook a randomised double-blind study to test the effects of ciprofloxacin treatment in children with shigella dysentery. METHODS: We compared the efficacy and toxic effects of ciprofloxacin suspension (10 mg/kg every 12 h for 5 days, maximum individual dose 500 mg) with those of pivmecillinam tablets (15-20 mg/kg every 8 h for 5 days, maximum individual dose 300 mg). We enrolled 143 children aged 2-15 years with dysentery of 72 h or less duration. Patients stayed in hospital for 6 days, and were followed up 7, 30, and 180 days after hospital discharge. Joint symptoms and function were assessed daily for 6 days. Clinical success was defined as the absence of frank dysentery on day 3, and on day 5 no bloody-mucoid stools, one or no watery stool, six or fewer total stools, and no fever. If no shigella were isolated from faecal samples on day 3 or thereafter, treatment was judged bacteriologically successful. FINDINGS: 13 patients were excluded since they did not meet eligibility criteria; 10 withdrew before day 5. Thus 120 patients (60 in each group) completed the study. Treatment was clinically successful in 48 (80%) of 60 patients who received ciprofloxacin and in 39 (65%) of 60 patients who received pivmecillinam (p=0.10). Treatment was bacteriologically successful in all of the patients receiving ciprofloxacin, and in 54 (90%) of the patients receiving pivmecillinam (p=0.03). Joint pain after treatment began in 13 (18%) of 71 patients who received ciprofloxacin and 16 (22%) of 72 patients who received pivmecillinam (p>0.2), and no patient had signs of arthritis. INTERPRETATION: In our trial, ciprofloxacin suspension and pivmecillinam had the same clinical efficacy. Ciprofloxacin had greater bacteriological efficacy and was not associated with the development of arthropathy. We conclude that ciprofloxacin is an effective and safe drug for use in multiply resistant childhood shigellosis.

Adolescent↗

Acinetobacter bacteremia in patients with diarrhoeal disease.

In 1994, 171 (27%) of all positive blood cultures in our hospital were due to Acinetobacter species. Of these, 138 cultures were considered significant, 91 (66%) were community-acquired and 47 (34%) were nosocomial. Most acinetobacter bacteraemia in children < or = 1 year old was community-acquired, while nosocomial infection was more common in children > 1 year old (P = 0.01). Most children < or = 5 years old were severely malnourished. The incidence of bacteraemia was lowest during the post-monsoon to early winter months. Acinetobacter bacteraemia associated mortality was twice (16%) that of all other patients (7.7%, P < 0.0005) and accounted for 4.5% of all hospital deaths during the study period. Bacteraemia caused by Acinetobacter species is an important cause of morbidity and mortality among our patient population with diarrhoeal disease.

Acinetobacter Infections↗

Novel large apolipoprotein E-containing lipoproteins of density 1.006-1.060 g/ml in human cerebrospinal fluid.

Although the critical role of apolipoprotein E (apoE) allelic variation in Alzheimer's disease and in the outcome of CNS injury is now recognized, the functions of apoE in the CNS remain obscure, particularly with regard to lipid metabolism. We used density gradient ultracentrifugation to identify apoE-containing lipoproteins in human CSF. CSF apoE lipoproteins, previously identified only in the 1.063-1.21 g/ml density range, were also demonstrated in the 1.006-1.060 g/ml density range. Plasma lipoproteins in this density range include low-density lipoprotein and high-density lipoprotein (HDL) subfraction 1 (HDL1). The novel CSF apoE lipoproteins are designated HDL1. No immunoreactive apolipoprotein A-I (apo A-I) or B could be identified in the CSF HDL1 fractions. Large lipoproteins 18.3 +/- 6.6 nm in diameter (mean +/- SD) in the HDL1 density range were demonstrated by electron microscopy. Following fast protein liquid chromatography of CSF at physiologic ionic strength, apoE was demonstrated in particles of average size greater than particles containing apoA-I. The largest lipoproteins separated by this technique contained apoE without apoA-I. Thus, the presence of large apoE-containing lipoproteins was confirmed without ultracentrifugation. Interconversion between the more abundant smaller apoE-HDL subfractions 2 and 3 and the novel larger apoE-HDL1 is postulated to mediate a role in cholesterol redistribution in brain.

Apolipoprotein A-I↗

Pattern of malignant tumors observed in a university hospital: a retrospective analysis.

A retrospective analysis of all malignant tumors observed in adults over a four-years period is presented. From January 1, 1989 to December 31, 1992, 2623 patients were coded by the Indexing and Coding Unit of Medical Records, The Aga Khan University Hospital to have cancer. Data presented reflect the relative frequency of different cancers seen at a single institution. Lung cancer was the commonest tumor observed in males. It was closely followed by head and neck cancer and lymphoma. In females, breast was the commonest cancer followed by ovarian and gallbladder. In comparison to the Western figures, an increased frequency of lymphomas and head and neck cancers was observed in males. Prostatic and colorectal cancers were less frequently observed. In females, gallbladder cancer is strikingly more frequent. Cervical cancer was less commonly observed as compared to the other developing countries and uterine cancer was infrequent in comparison to the Western countries. These data carry important implications for future health planning.

Adolescent↗

Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial.

BACKGROUND: Treatment of shigellosis is currently limited by the high prevalence of multidrug-resistant strains of Shigella. OBJECTIVE: To determine the efficacy of azithromycin in the treatment of shigellosis. DESIGN: Randomized, double-blind clinical trial. SETTING: Diarrhea treatment center in Dhaka, Bangladesh. PATIENTS: 70 men with shigellosis that had lasted 72 hours or less. INTERVENTIONS: Patients stayed in the hospital for 6 days. Thirty-four patients were randomly assigned to receive 500 mg of azithromycin on study day 1, followed by 250 mg once daily for 4 days; 36 patients were assigned to receive 500 mg of ciprofloxacin every 12 hours for 5 days. MEASUREMENTS: Clinical treatment failure was considered to have occurred if frank dysentery persisted for 72 hours after therapy began or if on study day 5 a patient had more than six stools, had any bloody-mucoid stools, had more than one watery stool, or had an oral body temperature exceeding 37.8 degrees C. Bacteriologic treatment failure was considered to have occurred if Shigella strains could be isolated from a stool sample after study day 2. Therapy was considered either clinically or bacteriologically successful in patients who completed therapy and did not meet criteria for failure. RESULTS: Therapy was clinically successful in 28 (82%) patients who received azithromycin and 32 (89%) patients who received ciprofloxacin (difference, -7% [95% Cl, -23% to 10%]). Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) patients receiving ciprofloxacin (difference, -6% [Cl, -14% to 2%]). Peak serum concentrations of azithromycin were equal to the minimum inhibitory concentration (MIC) of the infecting Shigella strains, whereas serum concentrations of ciprofloxacin were 28 times the MIC. Stool concentrations of both drugs were more than 200 times the MIC. CONCLUSION: Azithromycin is effective in the treatment of moderate to severe shigellosis caused by multidrug-resistant Shigella strains.

Adolescent↗

The increasing burden of disease in Bangladeshi children due to Haemophilus influenzae type b meningitis.

A laboratory-based study of diagnosed bacterial meningitis in the national paediatric hospital identified 852 cases of meningitis in the 8-year period 1987-1994. There were 587 culture-positive cases, of which Haemophilus influenzae (47%) and Streptococcus pneumoniae (32%) accounted for 80%. H. influenzae showed a remarkable increase of 700% during the study period. Most of the H. influenzae cases (90%) occurred in the 1st 2 years of life. Analysis of culture-negative specimens by antigen detection in the last 2 years also revealed the predominance of H. influenzae (71.4%) and S. pneumoniae (22.4%). Typing of H. influenzae isolates during this time showed that 98% of the strains were type b. This retrospective hospital-based study indicated a pronounced increase in the incidence of H. influenzae meningitis and strongly supports the need for large-scale Hib vaccination for young children. However, such nationwide intervention will probably need to be based on a prospective on a prospective and population-based surveillance of H. influenzae infections.

Age Distribution↗