PubMed HealthSearch

Biomedical subjects

G H Rabbani

Publications and source records attributed to G H Rabbani.

At least 19 recordsLinked to original sources

Development of an improved animal model of shigellosis in the adult rabbit by colonic infection with Shigella flexneri 2a.

Rabbits are not usually susceptible to intestinal Shigella infection without extensive pretreatment, including starvation and administration of antimicrobial, antimotility, and toxic agents (carbon tetrachloride). Most animals infected this way die rapidly and do not always develop colonic lesions and signs of dysentery. We describe here a successful experimental infection in the adult rabbit which does not require preparatory treatment and which reproduced characteristic features of human shigellosis. Unstarved, untreated adult rabbits were infected by direct inoculation of virulent Shigella flexneri 2a (10 ml of 10(7) bacteria per ml) into the proximal colon after ligation of the distal cecum (cecal bypass). Within 24 h of infection, most inoculated animals consistently developed clinical dysentery, characterized by liquid stool mixed with mucus and blood, leukocytosis, anorexia, and weight loss. Histologically, there were edema, exudation, superficial ulceration, and polymorphonuclear infiltrations in the lamina propria; crypt abscess formation; focal hemorrhages; and the presence of immunohistochemically stained S. flexneri in the colonic mucosa. Successful bacterial colonization was indicated by the isolation of the challenge strain of S. flexneri 2a from the colonic contents. None of the control rabbits challenged with nonvirulent S. flexneri or without cecal bypass developed dysentery or colitis. We conclude that successful Shigella infection can be induced by direct colonic inoculation with virulent S. flexneri 2a in adult rabbits without starvation and pretreatment. The colitis is dependent on the virulence of the bacteria and on the cecal bypass. This model should be useful in studies of the immunopathogenesis of Shigella infection.

Animals

Indomethacin decreases jejunal fluid secretion in addition to luminal release of prostaglandin E2 in patients with acute cholera.

Human cholera is associated with an increased luminal release of prostaglandin E2 (PGE2), but whether inhibition of increased PGE2 synthesis will reduce or control intestinal secretion is uncertain. 'Steady state' perfusions (10 ml/minute) in 12 patients with acute cholera, and repeat perfusions in nine of these patients during the convalescent phase were therefore performed using the triple lumen technique. The proximal jejunum was perfused with isotonic saline containing sodium-sulphobromophthalein as a non-absorbable marker. After intravenous administration of indomethacin (1.0 mg/kg) the jejunal net transfer of fluid and the jejunal flow rate of PGE2 were determined in 30 minute periods for 120 minutes after a 120 minute control period. Indomethacin decreased net fluid secretion (2.1 (0.3-4.2) v 4.5 (2.5-8.4) ml/hour x cm; medians, Q50 ranges, p less than 0.01) and the jejunal flow rate of PGE2 (1.5 (1.2-2.7) v 2.2 (1.4-4.9) ng/minute, p less than 0.05). The results of similar perfusion studies in 22 patients with acute cholera, used to establish the spontaneous time related change in fluid secretion, showed no significant change in net fluid transfer (3.5 (2.2-6.2) to 3.5 (2.6-11.6) ml/hour x cm, p greater than 0.25) over 240 minutes. These data provide further evidence in favour of the hypothesis that prostaglandins have a role in the cholera toxin induced intestinal fluid secretion in man.

Adult

Short-chain glucose polymer and anthracene-9-carboxylic acid inhibit water and electrolyte secretion induced by dibutyryl cyclic AMP in the small intestine.

Glucose-stimulated sodium absorption is the rationale for treatment with glucose-based oral rehydration solution in diarrhea. Concurrent treatment with pharmacological inhibitors, which specifically block chloride secretion, may be a useful adjunct to oral fluid therapy. To examine this hypothesis, the authors determined the intestinal water and ion transport rates in rat small intestine during the secretory phase induced by perfusion with N6-2'-0-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP), 1.0 mmol/L. A marker (polyethylene glycol 4000) dilution technique was used to evaluate the antisecretory effects of a defined short-chain glucose polymer, D-glucose, and a chloride channel blocker, anthracene-9-carboxylic acid (A-9-C). The results showed that dbcAMP induced small intestinal water and chloride ion secretion rapidly and reliably. The 2.5% concentration of rice short glucose polymer (G2, 22.7%; G3, 28.2%; G4, 14.0%; G5, 16.6%; G6, 11.6%; G7-9, 6.9%) is a better carbohydrate than the 2.5% concentration of D-glucose in reversing secretion of water, chloride, and sodium ions induced by dbcAMP. The combination of A-9-C and the glucose polymer can reverse dbcAMP-induced intestinal secretion and produces significantly (P less than 0.05) better antisecretory effect on water, sodium, and chloride ions than D-glucose with A-9-C.

Animals

Efficacy of a single dose of furazolidone for treatment of cholera in children.

To test the efficacy and safety of furazolidone given as a single dose for childhood cholera, a randomized double-blind placebo-controlled trial was carried out among 118 culture-positive dehydrated children with diarrhea. Patients were randomly assigned to one of four groups to receive medication orally in liquid suspension: furazolidone at 7 mg/kg/day once, furazolidone at 7 mg/kg/day divided into four doses for 3 days, placebo once, or placebo for 3 days. After 12 patients with furazolidone-resistant infections were excluded from the analysis of efficacy, it was determined that both groups treated with furazolidone showed significantly higher rates of bacteriologic success (stool cultures negative for Vibrio cholerae on days 2 to 4 after start of therapy) and clinical success (cessation of diarrhea within 72 h after start of therapy) than corresponding placebo groups (P less than 0.001). There were no significant differences between responses to the 3-day and single-dose regimens of furazolidone, but there was a trend toward better clinical responses in patients who received furazolidone for 3 days. No patient treated with furazolidone dropped out because of side effects. These results indicate that furazolidone, given as either a single dose or divided doses for 3 days, is effective treatment for childhood cholera.

Adolescent

A double-blind, controlled trial of bioflorin (Streptococcus faecium SF68) in adults with acute diarrhea due to Vibrio cholerae and enterotoxigenic Escherichia coli.

The therapeutic efficacy of Bioflorin (Streptococcus faecium SF68; Gipharmex, Milan, Italy) in acute watery diarrhea was evaluated in 183 Bangladeshi adults. Vibrio cholerae organisms were isolated from stool cultures in 114 patients, and enterotoxigenic Escherichia coli organisms were isolated in 41. In addition to IV rehydration, patients were randomly assigned to receive either capsules of Bioflorin containing 1 X 10(9) of live SF68 or capsules of placebo containing killed SF68 once every 8 hours for 3 days. No other drugs were allowed during this period. Bioflorin was well tolerated. It is concluded that Bioflorin has no demonstrable antidiarrheal property in adults with acute diarrhea due to V. cholerae or enterotoxigenic E. coli infection.

Adult

Low gastric acid as a risk factor for cholera transmission: application of a new non-invasive gastric acid field test.

Although gastric acid is thought to be an important host defense against certain enteric infections, field studies of the role of gastric acid in preventing enteric infections have been hampered by the lack of a suitable non-invasive test. Because low gastric acid output (GAO) is an established risk factor for cholera, we assessed after validation, whether a new non-invasive test which estimates GAO by measuring breath hydrogen excess after ingestion of magnesium and a stimulant of gastric acid secretion, could discriminate between persons at high and at low risk of developing cholera. Fifteen age-matched pairs, participants in the field trial of two oral cholera vaccines in rural Bangladesh, were tested. In each pair the "case" was a person who had recovered from severe cholera at least 6 months before testing and the "control" was a person who resided in the home of a cholera patient but remained uninfected. The stimulated breath hydrogen was higher in controls (median hydrogen excess = 369 mumol/80 min) than in cases (median hydrogen excess = 150 mumol/80 min) (p less than 0.05) and was higher in controls in 12 out of 15 pairs. The results, which are consistent with past invasive assessments of the association between hypochlorhydria and cholera, suggest that this non-invasive test may be useful in evaluating GAO in epidemiological field studies.

Adult

Clinical trial of clonidine hydrochloride as an antisecretory agent in cholera.

Clonidine hydrochloride (an alpha 2-adrenoceptor agonist) was tested for antisecretory effects in patients with cholera in a randomized controlled trial. Nineteen adults with diarrhea due to Vibrio cholerae were treated with clonidine (0.9 mg/24 h orally for 72 h) and 18 served as controls. During the first 24 h of treatment and for 24 h afterwards, the mean +/- SD concentrations of sodium (in millimoles per liter) in the stools of clonidine-treated patients were 120.6 +/- 10.9 and 112.3 +/- 11.9, which were significantly lower than 135.5 +/- 17.1 and 125.0 +/- 16.4 in the controls (p less than 0.01). Stool chloride concentrations (in millimoles per liter) were also significantly less in the clonidine group during the same periods: 82.1 +/- 16.8 and 62.4 +/- 19.4 vs. 92.1 +/- 18.3 and 78.0 +/- 23.0, respectively (p less than 0.05). Concentrations of potassium but not bicarbonate were also significantly reduced in the stools of clonidine-treated patients (p less than 0.05). However, there were no significant differences in the mean +/- SD stool volumes (in liters) between the clonidine and the control group in any of the six 12-h periods after treatment or in the cumulative volumes in 72 h (24.2 +/- 10.6 and 22.9 +/- 8.3, respectively). We conclude that clonidine causes modest reduction of stool electrolyte loss but does not significantly reduce fecal fluid loss in patients with cholera.

Adult

Single-dose treatment of cholera with furazolidone or tetracycline in a double-blind randomized trial.

To evaluate single doses of 400 mg of furazolidone and 1 g of tetracycline given orally to patients with diarrhea due to Vibrio cholerae, we studied 87 adults in a randomized, double-blind, placebo-controlled trial. All patients received intravenous fluids for rehydration and no other drugs. The total volumes of stool (mean +/- standard deviation) during a 6-day period after treatment were significantly smaller in the tetracycline group (10.5 +/- 8.6 liters) than in the furazolidone group (20.9 +/- 15.9 liters) and the placebo group (19.1 +/- 10.5 liters) (P less than 0.01). The duration of diarrhea and volumes of intravenous fluids were also significantly reduced in the tetracycline group (P less than 0.05). However, there were no differences between the furazolidone and the placebo groups with regard to stool volume, intravenous fluid, and duration of diarrhea. Within 48 h of treatment, tetracycline significantly reduced the number of patients with positive stool cultures for V. cholerae (37%) compared with furazolidone treatment (96%) and the placebo (97%) (P less than 0.001). Although the tetracycline group had a significantly higher incidence (61%) of bacteriologic relapse (negative stool cultures on days 2 and 3, followed by positive cultures afterward) compared with that in the furazolidone group (40%) and the placebo group (33%), this was not associated with clinical relapse. There were no differences between the furazolidone and placebo groups with regard to any of the bacteriologic responses examined. These data indicate that a single dose of 1 g of tetracycline is effective in the treatment of cholera, but it is asymptomatic bacteriologic relapse. A single dose of 400 mg of furazolidone is not therapeutically effective in cholera.

Adult

Orally administered bovine colostral anti-cholera toxin antibodies: results of two clinical trials.

PURPOSE: Previous reports have suggested that binding of luminal toxin by orally administered antitoxin antibodies might be a feasible treatment for cholera. We therefore conducted two randomized, controlled clinical trials to test the therapeutic efficacy of orally administered anti-cholera toxin bovine colostral immunoglobulins in patients with cholera diarrhea. PATIENTS AND METHODS: In Trial I, 45 patients with cholera were randomly assigned to receive two doses (2 g in 100 ml of water each) of anti-cholera toxin bovine colostral immunoglobulins, non-immune bovine colostral immunoglobulins, or 100 ml of water alone. In Trial II, 20 patients were randomly assigned to receive either 2 g of anti-cholera toxin bovine colostral immunoglobulins or non-immune bovine colostral immunoglobulins or water every two hours for a total of eight doses. The mean stool volumes in each of two sequential eight-hour periods following initiation of therapy were not significantly different among study groups in either trial. RESULTS: Measurement of immunoglobulin in stools showed that bovine IgG was detected in 19 of 25 patients given bovine colostral immunoglobulins in both trials. Cholera toxin neutralizing activity, as assessed with the rabbit ileal loop assay, was found in the stools of three of seven patients given anti-cholera toxin bovine colostral immunoglobulins in Trail I, and in all six patients given anti-cholera toxin bovine colostral immunoglobulins in Trail II. CONCLUSION: We conclude that oral anti-cholera toxin bovine colostral immunoglobulins are not effective in the treatment of patients with active cholera diarrhea. The prophylactic benefit of oral antitoxin antibody remains to be determined.

Administration, Oral

Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae.

To evaluate the antisecretory activity of berberine sulfate (BS), we studied 165 adult patients with acute diarrhea due to enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in randomized controlled trials. In patients with ETEC diarrhea who received 400 mg of BS in a single oral dose, the mean stool volumes were significantly less than those of the controls during three consecutive 8-hr periods after treatment (P less than .05). At 24 hr after treatment, significantly more patients who were treated with BS and had ETEC diarrhea stopped having diarrhea as compared with the controls (42% vs 20%, P less than .05). In patients with cholera who received 400 mg of BS, the mean 8-hr stool volume during the second 8-hr period after treatment declined to 2.22 liters, which was significantly less than the 2.79 liters found in the controls (P less than .05). However, patients with cholera who received 1200 mg of BS plus tetracycline did not have significant reduction in stool output compared with patients who received tetracycline alone. No side effects of BS were noted. These results indicated that BS is an effective and safe antisecretory drug for ETEC diarrhea, whereas the activity against cholera is slight and not additive with tetracycline.

Adult

The acidosis of cholera. Contributions of hyperproteinemia, lactic acidemia, and hyperphosphatemia to an increased serum anion gap.

To study the metabolic acidosis that occurs during the diarrhea of cholera, we examined the serum anion gap in 21 patients with hypovolemic shock due to Vibrio cholerae infection. Measurements of serum electrolytes, as well as divalent cations and the anionic contributions of serum proteins, lactate, phosphate, and serum creatinine, were made at the time of admission, after rehydration, and during convalescence. At the time of admission, the mean serum concentration of sodium was 134.8 mmol (meq) per liter, that of chloride was 103.2 mmol per liter, and that of bicarbonate was 11.4 mmol per liter; the mean anion gap was 20.2 mmol per liter. The mean serum creatinine concentration was 2.48 mg per deciliter. The low serum bicarbonate level and the high serum anion gap were corrected by rehydration. The increased serum anion gap was caused by hyperproteinemia, lactic acidemia, and hyperphosphatemia, with anionic contributions to the rise in anion gap estimated as protein, 5.5 meq per liter; lactate, 2.5 meq per liter; and phosphate, 2.5 meq per liter. The hyperproteinemia was attributed to dehydration, the lactic acidemia to shock, and the hyperphosphatemia to acidosis and transient renal failure. The mean concentrations of serum calcium and magnesium were slightly elevated but did not affect the increased anion gap. These results indicate that severe cholera causes acidosis with relatively little change in serum chloride but an increased serum anion gap. The acidosis is more profound than would be expected on the basis of stool losses of bicarbonate, because of superimposed lactic acidemia and renal failure.

Acid-Base Equilibrium

Cholera.

Explore the source record for details and available documents.

Adenosine Monophosphate

Indomethacin and chloroquine fail to inhibit fluid loss in cholera.

A randomized, controlled trial was conducted to investigate the ability of indomethacin and chloroquine to reduce intestinal secretion in 29 adult patients with severe cholera. All patients received intravenous infusion to restore fluid balance, but no antibiotics were given. Patients treated with oral indomethacin (total 200 mg) and chloroquine (total 1.5 g) did not have significantly different stool output than untreated controls during the five 8-h posttreatment periods (40 h).

Adult

The treatment of Fasciolopsis buski infection in children: a comparison of thiabendazole, mebendazole, levamisole, pyrantel pamoate, hexylresorcinol and tetrachloroethylene.

Four relatively new broad spectrum anthelmintics (thiabendazole, mebendazole, levamisole and pyrantel pamoate) were compared with two older anthelmintics, (tetrachloroethylene and hexylresorcinol) to treat heavy Fasciolopis buski infections in 17 children aged 4-13 years in hospital. Tetrachloroethylene was the most effective drug in these 17 children and another 49. Large numbers of worms were expelled and faecal egg counts were markedly reduced (99%). The mean number of worms per child was 122 with a range of 7 to 818. All the other anthelmintics tested were ineffective; no worms or only a few were expelled after treatment. However, the oral administration of tetrachloroethylene and hexylresorcinol were associated with severe anaphylactic reactions which were prevented by prior treatment with antihistamines.

Adolescent

Increased jejunal prostaglandin E2 concentrations in patients with acute cholera.

Supraphysiologic doses of prostaglandins (PGs) mimic the effect of cholera toxin and cAMP in the small intestine, but not all observations are explicable in terms of the theory that links PGs to cAMP. Because no data exist on endogenous PGs in human cholera we measured PGE2 concentrations in jejunal fluids and fasting intestinal flow rates of PGE2 during slow marker perfusion of proximal jejunum in nine patients with high purging cholera. Nine patients in the recovery phase of cholera or other watery diarrhoeas served as controls. In acute cholera PGE2 concentrations were significantly (p less than 0.001) raised (172-1435 (n = 9) vs 60-270 (n = 9) pg/ml) and negatively correlated (r = 0.71; p less than 0.05) to the time following onset of diarrhoea. Also fasting jejunal flow rates of PGE2 were significantly (p less than 0.005) increased (0.77-8.22 (n = 7) vs 0.21-0.92 (n = 6) ng/min), and positively correlated (r = 0.84; p less than 0.01) to stool output (2.9-9.5 ml/min). By extrapolation, at normal stool output fasting jejunal flow rates of PGE2 equalled those measured during convalescence. The results support the notion that PGs, in addition to cAMP, may play a pathophysiologic role in human cholera. As the ratio between the medians of the highest values measured during the acute phase of cholera and in late convalescence was at least 15, local intestinal PGE2 formation in full blown cholera should result in mucosal PGE2 concentrations above those required for a maximal secretory response. This observation might explain why conventional doses of aspirin and indomethacin had no significant antidiarrhoeal effect in clinical trials.

Acute Disease

Oral rehydration solution safely used in breast-fed children without additional water.

Sixty-four children of age 3 months to 2 years were treated for diarrhoea in a rural treatment centre with oral rehydration solution (90 mmol/l Na+); plain water was not supplied during rehydration. All children continued breast-feeding during the therapy. Serum sodium levels after 24 h of intake indicated that 61 children had serum sodium level below 148 mmol/l and three were above (range 150-151). None of the children developed clinical signs or symptoms of hypernatremia. The use of additional water may not be necessary during rehydration therapy of breast-fed children.

Breast Feeding

Controlled trial of chlorpromazine as antisecretory agent in patients with cholera hydrated intravenously.

A randomised controlled trial was conducted to investigate the ability of chlorpromazine to reduce intestinal secretion in cholera. Chlorpromazine had reduced loss of intestinal fluid in animals with diarrhoea induced by cholera toxin, and in a preliminary study the drug had reduced purging in patients with cholera. Forty-six adults with cholera were included in the randomised trial. Of these, 34 were treated with chlorpromazine (1 mg/kg or 4 mg/kg either by mouth or intramuscularly) and 12 served as controls. After treatment with the drug there was a significantly greater reduction in the rate of fluid loss in the treated patients than in the controls during the first (p less than 0.005), second (p less than 0.05), and fourth (p less than 0.01) eight-hour periods, but not during the third eight-hour period; the dose of 4 mg/kg was only marginally more effective than 1 mg/kg. The effect of chlorpromazine was strikingly biphasic, with one peak during the first eight hours and another 24-32 hours after administration. Chlorpromazine also significantly reduced the duration of diarrhoea, frequency of vomiting, and amount of intravenous fluid required. The drug induced mild sedation and no hypotension in these well-hydrated patients. These findings confirm the effectiveness of chlorpromazine in reducing fluid loss in cholera. A sedative effect, however, especially in children, may limit its usefulness and requires further study.

Adult