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Biomedical subjects

Rakesh Aggarwal

Publications and source records attributed to Rakesh Aggarwal.

At least 19 recordsLinked to original sources
PubMed2006

Does co-infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children?

BACKGROUND: This study looked at the frequency of co-infection with multiple hepatotropic viruses and the effect of such infection on the course and outcome of acute sporadic viral hepatitis (AVH) and fulminant hepatic failure (FHF) in children. METHODS: Consecutive children up to 15 years of age presenting with AVH or FHF between January 1998 and July 2002 were evaluated prospectively. The following viral markers were assessed in all children: immunoglobulin M (IgM) anti-hepatitis A virus (HAV), IgM anti-hepatitis E virus (HEV), hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core (HBc), and anti-hepatitis C virus (HCV). RESULTS: A total of 149 children were included in the study, 122 with AVH and 27 with FHF. Co-infection with multiple viruses was detected in 30 (24.6%) AVH patients (A+E in 24, A+B in three, and E+B, A+C and A+E+B in one each) and seven (26%) FHF patients (A+E in five, and A+B and E+B in one each). The majority of single infections were due to HAV (AVH 70/92, FHF 14/20) followed by HEV (AVH 9/92, and FHF 5/20). HEV infection was associated with infection with another agent in 88% of patients with AVH (odds ratio 53, 95% confidence interval 15-186, P<0.0001). Frequency of anicteric state, prolonged cholestasis, relapsing hepatitis, ascites, hemolysis and mortality rates were similar in the single and multiple infection groups for both AVH and FHF patients. CONCLUSIONS: Co-infection with multiple viruses is observed in one-quarter of patients with sporadic AVH in childhood. Such infection does not produce a more severe disease. HEV positivity is a strong marker for multiple infections.

Adolescent↗
PubMed2005

Immunological alterations in pregnant women with acute hepatitis E.

BACKGROUND: Infection with hepatitis E virus (HEV) is a major cause of acute viral hepatitis in several developing countries. Although usually self-limiting and benign, the disease is particularly severe among pregnant women, with mortality rates reaching 15-20%. METHODS: Immune parameters among pregnant women with acute hepatitis E (P-HEV) were investigated and compared with those in non-pregnant patients with hepatitis E (N-HEV), and healthy pregnant (PC) and non-pregnant (NPC) women. RESULTS: Peripheral blood mononuclear cells (PBMC) from P-HEV patients had lower lymphocyte proliferation response to phytohemagglutinin (PHA) than those in the PC and NPC groups. A positive lymphocyte proliferation response to HEV antigen (HEVAg), a mixture of eight peptides derived from HEV proteins, was observed in 7/19 (37%) P-HEV patients, 3/9 (33%) N-HEV patients and only 2/21 (10%) PC and 2/14 (14%) NPC subjects; the stimulation indices in the P-HEV group were similar to the N-HEV group and higher than the PC group. Measurement of cytokine production by PBMC in response to PHA and HEVAg showed a reduction in production of T-helper 1 (Th1) cytokines and an increase in that of Th2 cytokines in the P-HEV group. Cytokine mRNA levels showed similar changes. CONCLUSION: These results show the existence of a Th2 bias in pregnant women with acute hepatitis E. The role of this Th2 bias in the greater severity of hepatitis E among pregnant women needs further investigation.

Acute Disease↗
PubMed2004

Severe ulcerative colitis: prospective study of parameters determining outcome.

BACKGROUND: One-third of patients with exacerbations of ulcerative colitis (UC) require colectomy and 1% die. Although several studies have reported parameters associated with failure of medical treatment, studies using multivariate analysis of various predictors are scanty. METHODS: Demographic, clinical and laboratory parameters within 48 h of admission of 50 consecutive patients (55 episodes) were prospectively recorded. Each episode was treated with intravenous hydrocortisone, antibiotics and fluid administration. The data of patients who failed to respond, deteriorated, developed complications requiring emergency surgery or died within 7 days of hospitalization, were compared with the data of those who responded during this period using Mann-Whitney U-test or chi-squared tests. Variables found to be significant on univariate analysis were entered into a multivariate model. RESULTS: Medical treatment failed in 10 of 55 episodes; eight had surgery (one died), another died with bowel perforation and peritonitis and one left hospital in a moribund state. Younger age, pedal edema, transverse colonic diameter >5 cm on abdominal radiograph, low hemoglobin, low serum albumin, high C-reactive protein, presence of fibrin degradation product (FDP) in serum, low serum fibrinogen, prolonged prothrombin time, Truelove-Witt's fulminant disease, and high clinical activity index were associated with failure of medical treatment on univariate analysis. All the above variables were significant by multivariate analysis except age, serum albumin level and presence of FDP. CONCLUSION: It may be possible to predict the failure of medical treatment in exacerbations of UC using a scoring system based on clinical parameters and simple laboratory tests.

Adolescent↗
PubMed2003

Piperacillin induced bone marrow suppression: a case report.

BACKGROUND: Piperacillin (and piperacillin/tazobactam) is a commonly prescribed antibiotic and is generally considered safe. We report a case of piperacillin induced bone marrow suppression. CASE PRESENTATION: A 19-year-old boy was being treated with piperacillin followed by piperacillin/tazobactam for infected pancreatic pseudocyst. After 21 days of treatment, he developed neutropenia and thrombocytopenia. These reversed promptly after stopping piperacillin/tazobactam. The time course of events suggested that piperacillin was the cause of bone marrow suppression in this patient. CONCLUSION: Bone marrow suppression is a serious adverse effect of piperacillin, which should be kept in mind while treating patients with this drug.

Adult↗
PubMed2003

Assessment of cost-effectiveness of universal hepatitis B immunization in a low-income country with intermediate endemicity using a Markov model.

BACKGROUND/AIMS: Most countries with high hepatitis B (HB) virus endemicity and most high-income countries have introduced immunization programmes against this infection. However, several low-income countries with intermediate HB endemicity have not done so. We performed a cost-effectiveness analysis of universal childhood HB immunization in such countries using India as an example, since available data on this aspect are limited. METHODS: Marginal cost of every life-year and quality-adjusted life-year (QALY) gained with universal HB vaccination was calculated using a Markov model. Two types of analyses (including and excluding expenditure on treatment of long-term complications of HB infection) were done. Several sensitivity analyses and Monte-Carlo simulation were performed. RESULTS: Universal immunization reduced the HB carrier rate by 71%, and increased the number of years and QALY lived by a birth-cohort by 0.173 years (61.072 vs. 60.899 years) and 0.213 years (61.056 vs. 60.843 years), respectively. Marginal costs were US$16.27 per life-year gained and US$13.22 per QALY gained, much lower than annual per capita income. One-way sensitivity analysis and Monte-Carlo simulation confirmed the robustness of the conclusions. CONCLUSIONS: Universal HB immunization is highly cost-effective in low-income countries with intermediate endemicity rates.

Cost-Benefit Analysis↗
PubMed2003

Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time.

BACKGROUND: In tropical sprue (TS), response to antibiotics may suggest a role for bacterial contamination of the small bowel, which is known in diseases with prolonged orocecal transit time (OCTT). METHODS: We studied 13 patients with TS (diagnosed by standard criteria) for frequency, nature and degree of bacterial contamination of the small bowel by quantitative culture of jejunal aspirate, glucose hydrogen breath test (GHBT), and OCTT by lactulose hydrogen breath test before and after treatment. Twelve patients with constipation-predominant irritable bowel syndrome (IBS) and 12 healthy subjects served as controls. RESULTS: Ten of 13 patients with TS had bacterial contamination compared with 3/12 with IBS (all aerobic, P < 0.05). Median colony count in TS (36 000 CFU/mL, 400 to > 100 000) was higher than IBS (700 CFU/mL, 100-1000, P < 0.05). Gram-negative aerobic bacilli were commonly isolated in TS but not in IBS. Median OCTT was longer in TS (180 m, 40 - 240) than IBS (110 m, 70 - 150, P = 0.008) and healthy subjects (65 m, 40 - 110, P = 0.0007, Wilcoxon rank sum test). Orocecal transit time in TS correlated with fecal fat (Spearman's rank correlation coefficient 0.69, P < 0.05). Orocecal transit time and fecal fat, repeated in 8/13 patients, decreased with treatment for TS (195 m, 130-240 vs 125 m, 90-200, P = 0.02; 8 g/24 h, 6.8-19.6 vs 7 g/24 h, 4.2-9, P = 0.04, respectively). CONCLUSION: Aerobic bacterial contamination of the small bowel is common in patients with TS. Prolonged OCTT in TS correlated with fecal fat and normalized in a subset of patients after treatment.

Adult↗
PubMed2003

Recurrent duodenal ulcer haemorrhage: a pharmacoeconomic comparison of various management strategies.

BACKGROUND: Duodenal ulcer (DU) bleeding has a 7 - 13% mortality rate and bleeding often recurs. Prevention of recurrence is, therefore, an important goal. Eradication of Helicobacter pylori or maintenance treatment with a proton pump inhibitor (PPI) may reduce recurrent DU bleeding. Economic comparison of these options is sparse. METHODS: After the control of index bleeding with endotherapy and drugs, three strategies were evaluated: empirical treatment for possible H. pylori infection followed by a PPI for 2 months; test for H. pylori, eradication if positive, maintenance PPI if negative; maintenance PPI alone. Probability and direct cost data were obtained from a Medline search and Indian hospitals, respectively. Cost-minimisation, cost-utility, one- and two-way sensitivity analyses and threshold values were evaluated. RESULTS: Treatment of H. pylori, particularly empirical, was the preferred strategy and dominated maintenance treatment with PPI. The test-and-treat strategy was better than the empirical treatment strategy only when the probabilities of H. pylori eradication, ulcer healing following eradication and of frequency of H. pylori infection in bleeding DU were less than 58, 73 and 58%, respectively. CONCLUSIONS: Eradication of H. pylori is preferred in preventing recurrent bleeding from DU.

Clinical Trials as Topic↗
PubMed2003

Hepatic encephalopathy in pregnancy.

Hepatic encephalopathy in pregnancy may be related to a wide variety of acute and chronic liver diseases, including acute viral hepatitis, acute fatty liver of pregnancy, pre-eclampsia-related liver injury, etc. Of these, hepatitis E virus infection is a particularly important cause in those developing countries where this infection is endemic. Etiological diagnosis can be made based on epidemiologic, clinical and laboratory findings. Treatment is usually similar to that of hepatic encephalopathy in the absence of pregnancy. Patients with acute fatty liver of pregnancy and pre-eclampsia-related liver injury may benefit from termination of pregnancy; the role of this treatment modality among patients with viral hepatitis has not been studied.

Adult↗
PubMed2002

Strongyloides stercoralis infestation associated with septicemia due to intestinal transmural migration of bacteria.

Strongyloides stercoralis infestation is common in the tropics and is usually asymptomatic. Patients with immunocompromised states may develop hyperinfection and fulminant disease. It has been suggested that bacteria accompany S. stercoralis during its passage across the bowel wall, resulting in systemic sepsis. Herein is a report on a 30-year-old man with S. stercoralis infestation and small bowel bacterial overgrowth presenting as malabsorption syndrome. He developed extensive duodenojejunal ulceration, septicemia and fatal hypokalemia. Blood and jejunal fluid grew Escherichia coli with the same antibiotic sensitivity patterns. This supports the hypothesis of migration of bacteria from the intestinal lumen as a cause of septicemia in patients with fulminant S. stercoralis infestation.

Adult↗
PubMedDate not supplied

Role of travel as a risk factor for hepatitis E virus infection in a disease-endemic area.

BACKGROUND: We undertook epidemiologic and laboratory studies during an epidemic of acute hepatitis in Sindri town, in District Dhanbad, Bihar in 1998. METHODS: A sample survey covering 201 randomly selected houses in the town was conducted during the epidemic, and records of patients admitted to the only large hospital in this town were reviewed. We also tested serum and stool specimens from some of the affected persons for hepatitis E virus (HEV) RNA and IgM anti-HEV antibodies. RESULTS: Of the 1088 persons residing in the surveyed houses, 82 (7.54%) had developed acute hepatitis during the outbreak. Attack rate was higher among male residents than among female residents (71/604 vs. 11/484; 11.75% vs. 2.27%; relative risk [RR] 5.17 [95% confidence interval 2.77-9.65]; p<10(-6)) and was the highest in the 10-29 year age group. Hospital admission data showed similar age and gender distribution. Disease occurrence had no relation with source of drinking water (handpump 7.56% vs. municipal tap 7.53%; p=ns), or with habit of boiling (RR 1.10 [0.61-1.98]; p=ns) or filtering (RR 0.59 [0.33-1.06]; p=ns) water before drinking. Jaundice occurred more frequently among persons who had traveled outside Sindri town during the last two months than among those who had not (26.4% vs. 4.7%; RR 5.67 [3.81-8.43]; p<10(-6)); this risk persisted after correction for age (Mantel-Haenszel weighted OR 6.74 [4.12-11.01]; p<10(-6)). Men traveled more frequently than women and were more often affected. In multivariate analysis, travel and male gender were the only two independent risk factors. Data from a hospital in a neighboring large city, Dhanbad, suggested that there was an outbreak of hepatitis in that city too at the same time. Seventy-three of the 1088 study subjects had history of jaundice in the past; disease attack rate among these persons (9.6%) was similar to that among those without such history (7.5%; RR 1.31 [0.49-2.98]; p=ns). Of the 13 sera tested, 10 were positive for IgM anti-HEV. HEV RNA was detected in 9 of the 12 stool specimens and 10 of the 13 sera tested. CONCLUSIONS: The hepatitis epidemic in Sindri was caused by HEV and had several features resembling those of previous HEV epidemics. However, the occurrence of hepatitis E showed a strong relationship with history of travel, a finding not hitherto described.

Adolescent↗
PubMedDate not supplied

Evidence for activation of cellular immune responses in patients with acute hepatitis E.

INTRODUCTION: Although acute hepatitis E virus (HEV) infection is known to induce IgM and IgG humoral host immune responses, little is known about occurrence of cellular responses in this infection. We looked for evidence of lymphocyte sensitization to HEV peptides in patients with acute HEV infection. METHODS: peripheral blood lymphocytes were obtained from patients with acute hepatitis E and healthy controls. Proliferation of these lymphocytes in the presence of each of seven peptides with amino acid sequences corresponding to open reading frames 2 and 3 proteins of HEV (3 and 4 peptides, respectively) were studied; no peptide was added to control wells. Proliferative responses with stimulation indices exceeding 3.0 were taken as positive. RESULTS: More patients showed reactivity to two or more HEV peptides than did controls (11/21 vs 5/22, p<0.05). Reactivity to one peptide corresponding to open reading frame 2 of HEV was more frequent in patients than in controls (7/21 vs 1/22, p<0.05). CONCLUSION: Our results show that lymphocytes of patients with acute hepatitis E show sensitization to HEV peptides. This may have significance in understanding the pathogenetic mechanisms of liver injury in this infection.

Acute Disease↗
PubMedDate not supplied

Treatment of chronic hepatitis B with interferon-alpha: cost-effectiveness in developing countries.

BACKGROUND: Treatment with interferon-alpha (IFN) has been shown to be cost-effective in developed countries. However, cost-effectiveness In developing countries such as India has not been studied. METHODS: Using the Markov transitional probability model, we studied two cohorts of young patients (30 years of age) with chronic hepatitis B, one untreated and the other treated with interferon (IFN), 5 million units daily for 16 weeks, with evidence of viral replication and chronic hepatitis, but not cirrhosis, and were followed up over a 30-year period. Rates of disease progression, efficacy of IFN and quality of life associated with various disease states were estimated from the available literature. Direct costs were estimated using Indian prices of IFN and from the usual costs of medical treatment in India based on expert opinion. Unrelated mortality rates were modelled on age-specific death rates of the general population. The efficacy of IFN was judged In terms of extra life-years and quality-adjusted life-years (QALY) gained, and marginal cost-effectiveness and cost-utility. Several sensitivity analyses, both undiscounted and with discounted analyses, were done. RESULTS: At the end of the 30-year period, fewer patients in the IFN-treated group developed cirrhosis or decompensated cirrhosis, or were dead. The average life span of the treated cohort was 25.14 years, a gain of 0.6 years over the untreated cohort (24.54years). The QALY lived bythetwocohortswere 23.69 and 22.75 years, respectively, representing a gain of 0.94 years for the IFN-treated group. The cost Incurred by the IFN-treated group was Rs 300,000, and that for the untreated cohort was Rs 40 700, a substantial difference. Using the baseline estimates, undiscounted costs per year of life gained and per QALY gained were Rs 432,500 and Rs 276,900, respectively; these estimates are 20.5 and 13.1 times the per capita gross national income of the Indian population. Sensitivity analyses showed that changes in various parameters led to only minor changes in these estimates. Use of discounting led to an increase in marginal cost per life-year or QALY gained. CONCLUSION: In developing countries with a low per capita Income, IFN therapy for chronic hepatitis B may not be cost-effective. A careful consideration of cost-effectiveness is therefore essential before Instituting IFN therapy in patients with chronic hepatitis B In such populations.

Adult↗
PubMedDate not supplied

Occult hepatitis B virus infection as a cause of cirrhosis of liver in a region with intermediate endemicity.

BACKGROUND: Serological tests may fail to identify hepatitis B virus (HBV) infection as a cause of liver cirrhosis in a proportion of patients. The frequency of such occult infection in regions with intermediate HBV endemicity is not known. Such cases may be diagnosed by incremental testing for IgG anti-HBc, serum HBV DNA, and HBV DNA in liver tissue. METHODS: We tested sera of 111 patients with cirrhosis, including 39 with history of significant alcohol ingestion, for HBsAg, anti-HBc and serum HBV DNA. In addition, in a subset of 14 patients, HBV DNA was looked for in liver tissue. RESULTS: On HBsAg and anti-HBc testing, 66 patients had HBV infection. Serum HBV DNA testing identified HBV infection in 13 additional cases. Of 18 patients labeled as 'cryptogenic' on serological testing, HBV DNA was detected in the serum in 7 patients. Of 14 patients in whom paired liver tissue and serum specimens were tested, 4 additional patients with HBV infection were detected after liver biopsy analysis. CONCLUSIONS: Serological tests for HBsAg and anti-HBc antibody are insensitive in identifying HBV infection in patients with liver cirrhosis. HBV DNA testing in serum and liver can help in establishing HBV infection as etiology, either alone or in addition to another cause.

Adult↗
PubMedDate not supplied

Frequency of infection by hepatitis B virus and its surface mutants in a northern Indian population.

INTRODUCTION: The reported prevalence of hepatitis B virus (HBV) infection in the Indian general population varies from 2% to 11%. Epidemiological studies conducted so far have selection biases, since these included populations of defined age group, gender, social class, high-risk group, etc. The present study was designed to look for the molecular epidemiology of HBV infection in the rural and urban general populations in India. METHODS: Sera obtained from healthy volunteers during college and social service camps from parts of northern India were tested for HBsAg and anti-HBc using enzyme immunoassays and for HBV DNA using polymerase chain reaction and Southern blot hybridization. The amplification products were cloned and sequenced, and nucleotide and deduced amino acid sequences of the surface and polymerase genes were analyzed for mutations. RESULTS: Of the 730 subjects (rural 543, urban 187), 15 (2.1%) tested positive for HBsAg and 143 (19.5%) for anti-HBc; 10 were positive for both. The overall HBV exposure rate in the population was 20.3% (148/730). The HBsAg carrier rate was similar in the urban and rural populations (1.5% and 2.3%; p=ns), and anti-HBc positivity was lower in the urban population (8.5% vs. 23.3%; p<0.01). History of parenteral interventions or blood transfusion was associated with markers of exposure to HBV (10.2% vs. 4.6%; p=0.01). Among the 220 representative samples tested for HBV DNA, 14 (6.4%) were positive; of these, only four were positive for HBsAg or anti-HBc. Sequencing of a 388-nt segment of the S-gene from three individuals (two adw and one ayw subtype) revealed four mutations. Two and three of these led to amino acid changes in the HBV surface and polymerase genes, respectively; alterations in known cytotoxic T cell epitopes of HBV surface and polymerase proteins were observed in one individual each. None had the G587A mutation, which is known to be associated with loss of the 'a' determinant of HBsAg. CONCLUSION: Our study shows a high frequency of exposure to HBV infection in the Indian general population; a proportion of HBV infected persons were detectable only by molecular methods. The positivity rate was higher in the rural population.

Adolescent↗