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Biomedical subjects

Y K Joshi

Publications and source records attributed to Y K Joshi.

At least 19 recordsLinked to original sources

Transfusion transmitted virus: A review on its molecular characteristics and role in medicine.

The present review gives an updated overview of transfusion transmitted virus (TTV), a novel agent, in relation to its molecular characteristics, epidemiological features, modes of transmission, tissue tropism, pathogenesis, role in various diseases and its eradication from the body. TTV, a DNA virus, is a single stranded, non-enveloped, 3.8 kb long DNA virus with a small and covalently closed circular genome comprising 3852 bases. It was tentatively designated Circinoviridae virus. TTV genome sequence is heterogeneous and reveals the existence of six different genotypes and several subtypes. TTV has been reported to transmit not only via parenteral routes, but also via alternate routes. This virus has been detected in different non-human primates as well. At present, TTV is detected by polymerase chain reaction (PCR) with no other available diagnostic assays. It shows its presence globally and was detected in high percent populations of healthy persons as well as in various disease groups. Initially it was supposed to have strong association with liver disease; however, there is little evidence to show its liver tropism and contribution in causing liver diseases. It shows high prevalence in hemodialysis patients, pointing towards its significance in renal diseases. In addition, TTV is associated with several infectious and non-infectious diseases. Though, its exact pathogenesis is not yet clear, TTV virus possibly resides and multiplies in bone marrow cells and peripheral blood mononuclear cells (PBMCs). Recently, attempts have been made to eradicate this virus with interferon treatment. More information is still needed to extricate various mysteries related to TTV.

Animals↗

Mother-to-child transmission of hepatitis E virus infection.

OBJECTIVES: Water borne or enterically transmitted non-A-non-B hepatitis is a major public health problem in India. Many of these cases carry fatal outcome. The hepatitis E virus (HEV) has been considered to be the most important causative agent of this entity. The severity and fatality rates of HEV infection are reported to be rather more in pregnant women. However, there is meager information from India, on mother to child transmission of this agent. METHODS: During 1997-98, we studied 60 pregnant women suspected to have acute viral hepatitis to understand the frequency of various viral etiologies, disease course and outcome of the pregnancy. Six cord blood samples were tested for IgG, and IgM antibodies against hepatropic viral agents and also for hepatitis E virus RNA by RT-nested PCR using ORF-1 as target. RESULTS: Of the 60 pregnant patients hospitalised at All India Institute of Medical Sciences, New Delhi for acute hepatitis, 22 (37%) were positive for IgM anti-HEV antibodies and 10% were infected with hepatitis B virus. Co-infection of HEV with Hepatitis B and C was seen in 1 and 2 patents, respectively. Most (72%) of the HEV infected patients were in third trimester of pregnancy (P<0.05). Of the 6 cord blood samples tested 3 (50%) were positive for HEV RNA. Though, all mothers were RNA positive, half of the babies did not get infected in utero with HEV. Fourteen of the 22 (63.6%) HEV infected mothers developed fulminant hepatic failure and all died. CONCLUSION: The mortality rate in HEV [corrected] infected mothers was 100%. Mother to child transmission of hepatitis E virus infection was established in 50%.

Adult↗

Cyclo-oxygenase 2 inhibitors: emerging roles in the gut.

BACKGROUND AND AIMS: Discovery of an isoform of Cyclo-oxygenase (COX) 1, the inducible COX-2, has made it possible to avoid some side effects of non-specific COX inhibitors. The COX-2 gene is over-expressed in reflux oesophagitis, Barrett's oesophagus, gastric and colon cancer, familial adenomatous polyposis, pancreatic cancer, hepatocellular carcinoma, hepatotoxicity, cirrhosis, and inflammatory bowel disease, and specific COX-2 inhibitors have been tried experimentally and clinically and found effective. METHODS: A Medline search was performed of English-language experimental studies and controlled clinical trials from January 1980 to January 2002, and relevant citations were noted. RESULTS: Review of available literature shows that sulindac and COX-2 inhibitors are effective in preventing as well as regressing familial adenomatous polyposis. However, they have not been shown to prevent cancer in these patients. Studies evaluating NSAIDs and COX-2 inhibitors in carcinogen-induced and genetically manipulated animal models of various cancers have been promising especially in conditions such as Barrett's oesophagus, oesophageal and hepatocellular carcinoma and pancreatic cancer. COX-2 inhibitors may be of value in the treatment of reflux oesophagitis, pancreatitis and hepatitis, although carefully planned randomized controlled clinical trials demonstrating their efficacy need to be conducted. At present NSAIDs and COX-2 inhibitors cannot be recommended for average-risk individuals or for those with sporadic colorectal neoplasia (or other forms of cancers) as chemo-preventive agents. CONCLUSION: COX-2 inhibitors may open up a new therapeutic era in which these drugs can be used for chemo-prophylaxis. However, COX-2 selective inhibitors retain renal adverse effects of the non-selective inhibitors and the concern regarding the pro-thrombotic potential of COX-2 inhibitors will limit their value as chemo-preventive agents.

Adenomatous Polyposis Coli↗

Auditory P300 event-related potentials and number connection test for evaluation of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: a follow-up study.

BACKGROUND AND AIMS: The P300 event-related potentials (P3ERP) have been recently advocated for detection of cognitive disturbances in early encephalopathy. However, no systematic follow-up study has been conducted to understand the clinical significance of subclinical hepatic encephalopathy (SHE) detected by this or other methods. The present study was therefore undertaken to examine the diagnostic usefulness of auditory P3ERP in the detection of SHE, to compare it with that of the number connection test (NCT), and to investigate the clinical outcome of patients with SHE in terms of progression to overt encephalopathy. METHODS: P300 event-related potential latencies were measured and the NCT time was recorded in 81 non-encephalopathic cirrhotic patients (Aged 43.8 +/- 11 years, 23 alcoholic and 58 non-alcoholics) attending the outpatient department at our tertiary care hospital (All India Institute of Medical Sciences Hospital). Cut-off values for abnormality in the tests were developed from age-, sex- and education-matched controls. Patients were followed up at regular intervals for the development of overt encephalopathy, and the identifiable precipitating factors were noted. The P3ERP latencies (363 +/- 34 msec vs 349 +/- 23 msec), as well as NCT time (54.6 +/- 30.6 s vs 39.5 +/- 15.8 s) were significantly prolonged (P< 0.01) in patients with liver cirrhosis when compared with the non-cirrhotic controls. RESULTS: The P3ERP defects were seen in 24.6% of cirrhotic patients, while NCT time was prolonged in 19.7% of the patients. Nearly 43% of the patients with SHE progressed to overt encephalopathy within a mean duration of 5 months, while only 3.9% of the non-SHE patients did so. Of the patients who developed overt encephalopathy, 64.2% had P3ERP latency prolongations while 35.7% had abnormal NCT. CONCLUSIONS: The results of the present study suggest that P3ERP and NCT are valid tools for the screening of SHE in cirrhotic patients as there is a greater likelihood of overt encephalopathy development in patients with an abnormality detected by these tests than in patients with no such abnormality.

Adolescent↗

Nutritional risk factors in esophageal cancer.

OBJECTIVE: The present case-control study was undertaken with the objective to study the nutritional risk factors associated with esophageal cancer. METHODOLOGY: One hundred and fifty diagnosed esophageal cancer patients and an equal number of healthy individuals constituted the patient and control groups, respectively. Dietary consumption pattern during the preceding 20 years prior to the diagnosis of esophageal cancer was assessed utilising the standard food frequency questionnaire method. Information on alcohol consumption, smoking habits, chewing of betel leaf with tobacco was also collected. RESULTS: Multivariate analysis revealed that the risk of esophageal cancer was 7.81 times (p < 0.01) higher with daily consumption of alcohol. The risk increased to 3.16 times (p < 0.01) with the daily habit of chewing of betel leaf with tobacco. Nearly a two fold risk was observed when the consumption of "other vegetables" was less than four times per week. A 1.95 times (p < 0.01) increase in risk was observed with the daily habit of bidi smoking. CONCLUSION: Cancers in general are multifactorial in origin, and several environmental interactions are possible. It is not easy to quantify the contribution of diet to cancer risk. However, the results of the present study suggested that nutritional factors do play a role.

Adult↗

Comparison of endoscopic variceal sclerotherapy with sequential endoscopic band ligation plus low-dose sclerotherapy for secondary prophylaxis of variceal hemorrhage: a prospective randomized study.

BACKGROUND: Endoscopic variceal sclerotherapy and band ligation both have certain limitations such as, respectively, esophageal complications and early recurrence of varices. METHODS: From February 1994 to March 1996, all consecutive patients with portal hypertension due to either cirrhosis or noncirrhotic portal fibrosis and a history of variceal bleeding were included in a prospective study and randomly assigned to receive either endoscopic variceal sclerotherapy alone or endoscopic variceal band ligation plus low-dose endoscopic variceal sclerotherapy. RESULTS: Of 69 patients, 34 were randomly assigned to receive endoscopic variceal sclerotherapy alone; 35 received endoscopic variceal band ligation plus endoscopic variceal sclerotherapy. Complete variceal eradication rates (85% vs. 80%) and the number of endoscopic sessions required for eradication (6.61 +/- 2.94 vs. 7.85 +/- 3.31) were similar in the endoscopic variceal sclerotherapy and endoscopic variceal band ligation plus endoscopic variceal sclerotherapy groups, respectively. The mean volume of sclerosant required in the combined group (54.94 +/- 33.74 mL) was significantly less than that in the endoscopic variceal sclerotherapy group (81.91 +/- 34.80 mL). The complication and recurrent bleeding rates were significantly higher in the endoscopic variceal sclerotherapy group than those in the combined group (20% and 16% vs. 3% and 3%, respectively). CONCLUSIONS: Both endoscopic variceal sclerotherapy and endoscopic variceal band ligation plus endoscopic variceal sclerotherapy were comparable in eradicating varices but the combined technique was associated with significantly lower complication and recurrent bleeding rates.

Adult↗

A prospective study on the incidence of hepatitis B & C infections amongst patients with lymphoproliferative disorders.

Fifty one patients with acute lymphoblastic leukaemia (ALL) and non-Hodgkins lymphoma (NHL) undergoing chemotherapy were studied prospectively to determine the incidence, aetiology and natural course of hepatitis. Of 51 patients (31 NHL and 20 ALL), 22 developed hepatitis. Hepatitis B (IgM anti HBc positive) was the cause in 11 patients (50%), hepatitis C in 4 patients, and septicaemia and cytotoxic drugs in 3 patients each. Malignant infiltration of the liver was the cause in the remaining 1 patient. Hepatitis was predominantly (75%) anicteric. Mean duration of hepatitis was 21 days. Of 51 patients, 21 acquired hepatitis B and/or C virus infection. They had received 6.4 (+/- 3.4) units of packed red cells and 5.3 (+/- 11) units of platelet concentrate as compared to 3.4 (+/- 4.8) units of red cells and 5.3 (+/- 12.1) units of platelet concentrate received by those who did not acquire virus infection (P < 0.05 for packed red cells). Only transient stoppage of chemotherapy was necessary following development of hepatitis and most of the patients who developed hepatitis could complete their chemotherapy schedule. None of the patients who developed viral B or C infection cleared the infection. We conclude that there was a high incidence of hepatitis B and C infection amongst patients with lymphoproliferative disorders with an increased carrier rate. Transfusion was a major risk factor for such infections.

Acute Disease↗

Fulminant hepatitis in a tropical population: clinical course, cause, and early predictors of outcome.

The profiles of patients with fulminant hepatic failure (FHF) from developing countries have not been reported earlier. The current study was conducted prospectively, at a single tertiary care center in India, to document the demographic and clinical characteristics, natural course, and causative profile of patients with FHF as well as to define simple prognostic markers in these patients. Four hundred twenty-three consecutive patients with FHF admitted from January 1987 to June 1993 were included in the study. Each patient's serum was tested for various hepatotropic viruses. Univariate Cox's regression for 28 variables, multivariate Cox's proportional hazard regression, stepwise logistic regression, and Kaplan-Meier survival analysis were done to identify independent predictors of outcome at admission. All patients presented with encephalopathy within 4 weeks of onset of symptoms. Hepatotropic viruses were the likely cause in most of these patients. Hepatitis A (HAV), hepatitis B (HBV), hepatitis D (HDV) viruses, and antitubercular drugs could be implicated as the cause of FHF in 1.7% (n= 7), 28% (n= 117), 3.8% (n= 16), and 4.5% (n= 19) patients, respectively. In the remaining 62% (n= 264) of patients the serological evidence of HAV, HBV, or HDV infection was lacking, and none of them had ingested hepatotoxins. FHF was presumed to be caused by non-A, non-B virus(es) infection. Sera of 50 patients from the latter group were tested for hepatitis E virus (HEV) RNA and HCV RNA. In 31 (62%), HEV could be implicated as the causative agent, and isolated HCV RNA could be detected in 7 (19%). Two hundred eighty eight (66%) patients died. Approximately 75% of those who died did so within 72 hours of hospitalisation. One quarter of the female patients with FHF were pregnant. Mortality among pregnant females, nonpregnant females, and male patients with FHF was similar (P > .1). Univariate analysis showed that age, size of the liver assessed by percussion, grade of coma, presence of clinical features of cerebral edema, presence of infection, serum bilirubin, and prothrombin time prolongation over controls at admission were related to survival (P < .01). The rapidity of onset of encephalopathy and cause of FHF did not influence the outcome. Cox's proportional hazard regression showed age > or = 40 years, presence of cerebral edema, serum bilirubin > or = 15 mg/dL, and prothrombin time prolongation of 25 seconds or more over controls were independent predictors of outcome. Ninety-three percent of the patients with three or more of the above prognostic markers died. The sensitivity, specificity, positive predictive value, and the negative predictive value of the presence of three or more of these prognostic factors for mortality was 93%, 80%, 86%, and 89.5%, respectively, with a diagnostic accuracy of 87.3%. We conclude that most of our patients with FHF might have been caused by hepatotropic viral infection, and non-A, non-B virus(es) seems to be the dominant hepatotropic viral infection among these patients. They presented with encephalopathy within 4 weeks of the onset of symptoms. Pregnancy, cause, and rapidity of onset of encephalopathy did not influence survival. The prognostic model developed in the current study is simple and can be performed at admission.

Adolescent↗

Prevalence of hepatitis C virus antibodies in the general population & in selected groups of patients in Delhi.

We report on the prevalence of anti-HCV antibodies in healthy individuals and patient groups with different liver diseases. The healthy population comprising 234 voluntary blood donors and 65 pregnant women with no history of liver diseases, had a per cent positivity of 1.5 anti-HCV in each group. The patients groups comprising 32 with acute viral hepatitis, 110 with fulminant hepatic failure, 65 with subacute hepatic failure, 33 with chronic active hepatitis, 45 with cirrhosis and 10 with hepatocellular carcinoma, had anti-HCV per cent positivity of 12.5, 43.6, 41.5, 48.5, 8.8 and 0 respectively. Anti-HCV was also tested in sera from 9 patients who had developed post-transfusion hepatitis and was recorded in 2 (22.2%) within one year of transfusion.

Blood Donors↗

Role of enteral hyperalimentation in patients of carcinoma oesophagus.

The nutritional status of 24 patients of carcinoma oesophagus was assessed before and after central hyperalimentation with a liquid blenderized diet containing 3000-3500 cal and 100-120 g protein. The overall prevalence of malnutrition was found to be 70.8 per cent before the initiation of therapy. Of the various parameters used for assessment of nutritional status weight loss was the most common finding (91.6%) followed by alteration in midarm circumference, haemoglobin, triceps skin fold thickness, midarm muscle circumference and serum albumin. Enteral hyperalimentation for 10 days improved nutritional status by inducing significant gain in body weight (74.1%), triceps skin fold thickness (50%), midarm circumference (58%), midarm muscle circumference (62.5%) and serum albumin levels (91.6%). There was no significant change in haemoglobin levels.

Adolescent↗

A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure.

The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure.

Adolescent↗

Prospective controlled study of post-transfusion hepatitis after cardiac surgery in a large referral hospital in India.

We studied the risk of post-transfusion hepatitis (PTH) in recipients of blood collected from voluntary donors screened for HBsAg. Two hundred and fifty patients without any previous history of liver disease or transfusion were followed up for 12 months subsequent to cardiac surgery. Thirty-five of them had closed-heart surgery without receiving transfusion and served as controls. The remaining 215 patients received single-point transfusions (mean 4 +/- 2.4 units). None of the controls and 15 (6.9%) blood recipients developed PTH. Three (20%) patients had hepatitis-B-virus-induced hepatitis while the remainder (80%) had non A, non B (NANB) hepatitis. The number of units of blood transfused and surrogate markers for development of PTH (donor alanine aminotransferase, anti-HBc and anti-HBs antibody) were not associated with the occurrence of PTH (p greater than 0.05). Nine (60%) of the 15 patients developing PTH were asymptomatic. All the patients recovered from the PTH, except one who died of fulminant hepatitis. At the end of 1 year of follow-up, none of the patients had evidence of chronic hepatitis. Only three (25%) of the patients with NANB-PTH developed anti-hepatitis C virus (HCV) antibody during the follow-up. We conclude that the incidence of PTH in India is similar to other parts of the world and NANB virus was the major cause of the PTH. The absence of chronicity and lack of seroconversion to anti-HCV antibody in the majority of the patients after 1 year of follow-up may suggest the possibility of a NANB virus other than HCV as the major cause of PTH in India.

Adolescent↗

Hepatitis C virus infection is the major cause of severe liver disease in India.

The present study describes the status of hepatitis C virus infection in 167 patients with severe forms of liver diseases in India. The anti-HCV positivity rate was recorded as 43%, 47%, and 42% in patients with FHF, SAHF, and CAH respectively. HBV and HCV coinfection was recorded in 28% of FHF, 43% of SAHF and 75% of the CAH cases. Superinfection of HCV in HBsAg carriers was recorded in the 54% cases of FHF, 60% of SAHF and 42% of the CAH. None of these 167 patients was positive of HAV-IgM. Further, 27.7% of FHF, 26.4% of SAHF and 15.2% of CAH cases were neither HBV nor HCV markers positive. These can be labelled as non-A, non-B and non-C infections.

Hepatitis B↗

Hepatitis B virus replication in patients with chronic liver diseases.

One hundred and seventy five subjects with chronic liver diseases which included patients with chronic active hepatitis (90), liver cirrhosis (31) and asymptomatic hepatitis B carriers (54), were included in the study. Hepatitis B virus (HBV) specific DNA-polymerase activity and HBe-markers were tested as markers of HBV-multiplication. In HBsAg positive samples, DNA-P activity was positive in 44.4% of the HBV carriers, 52.9% of the patients with chronic active hepatitis and 81.8% of the patients with liver cirrhosis. The corresponding figures for the presence of HBeAg in these groups were 18.5, 26.5 and 45.5% respectively. Virus multiplication was also observed in 41.1 and 44.4% patients with chronic active hepatitis and liver cirrhosis respectively, in the absence of HBsAg. The results of the present study show that hepatitis B virus is the most important etiological factor of chronic liver diseases in India. Most of our patients of chronic liver diseases seems to have contacted HBV infection as young adults and the mode of transmission is likely to be horizontal rather than vertical. The virus replicating markers correlate well with the severity of the liver injury and decreased with the age. DNA-P activity is a more sensitive marker of viral multiplication than HBeAg. Viral multiplication was also found to occur in the absence of the usual HBV markers. Continued viral multiplication in patients with chronic active hepatitis and liver cirrhosis is implicated in continued liver injury and progressive liver disease.

Adolescent↗

Significance of anti-pre-S antibodies in patients with fulminant hepatic failure.

Anti-pre-S antibody was tested in 38 sera from patients with fulminant hepatitis (positive for HBsAg and/or IgM anti-HBc) using a specific solid phase enzyme linked immunosorbent assay (ELISA). Anti-pre-S activity was detected in 50 percent sera samples positive for HBsAg but negative for IgM anti-HBc. There were 12.5% sera positive for both HBsAg as well as IgM anti-HBc and 75% sera negative for HBsAg but positive for IgM anti-HBc. The prevalence of HBV-specific DNA-polymerase activity was high in all the three groups whereas anti-HBs positivity was low. Anti-pre-S activity was observed both in the presence as well as in the absence of DNA-polymerase activity. High-anti-pre-S level in fulminant hepatitis B patients was assumed to be implicated in the fast clearance of HBsAg from circulation.

Hepatic Encephalopathy↗