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 patients, 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 infectedin utero with HEV. Fourteen of the 22 (63.6%) HEV infected mothers developed fulminant hepatic failure and all died.Conclusion : The mortality rate in HIV infected mothers was 100%. Mother to child transmission of hepatitis E virus infection was established in 50%     

SQUID biosusceptometry in the measurement of hepatic iron

Individuals with primary or secondary abnormalities of iron metabolism, such as hereditary hemochromatosis and transfusional iron loading, may develop potentially lethal systemic iron overload. Over time, this excess iron is progressively deposited in the liver, heart, pancreas, and other organs, resulting in cirrhosis, heart disease, diabetes and other disorders. Unless treated, death usually results from cardiac failure. The amount of iron in the liver is the best indicator of the amount of iron in the whole body. At present, the only sure way to measure the amount of iron in the liver is to remove a sample of the liver by biopsy. Iron stored in the liver can be magnetized to a small degree when placed in a magnetic field. The amount of magnetization is measured by our instrument, called a superconducting quantum interference device (SQUID) susceptometer. In patients with iron overload, our previous studies have shown that magnetic measurements of liver iron in patients with iron overload are quantitatively equivalent to biochemical determinations on tissue obtained by biopsy. The safety, ease, rapidity, and comfort of magnetic measurements make frequent, serial studies technically feasible and practically acceptable to patients.     

Anti-Helicobacter pylori therapy in India: differences in eradication efficiency associated with particular alleles of vacuolating cytotoxin (vacA) gene

BACKGROUND AND AIMS: The efficiency of Helicobacter pylori eradication varies geographically, as do many parameters that might affect therapeutic efficiency, including bacterial genotype. The aim of the present study was to determine the efficiency of H. pylori eradication using a 10-day proton pump inhibitor-based triple-therapy regimen (omeprazole, clarithromycin and amoxycillin) in an eastern Indian patient population, and to find out the relationship, if any, of the success or failure of the therapy to known features of bacterial genotype. METHODS: Helicobacter pylori infections were analyzed in 66 duodenal ulcer patients by upper gastrointestinal endoscopy, rapid urease tests, histology and culture. The cytotoxin-associated gene (cagA) and vacuolating cytotoxin (vacA) gene status of cultured strains were studied by polymerase chain reaction. Treatment was given for 10 days and endoscopy was repeated at 4 and 12 weeks post therapy to monitor ulcer healing and H. pylori eradication. RESULTS: Ulcer healing was observed in 60 patients (96.77%). Helicobacter pylori was eradicated in 41 (62.12% intention to treat, 66.13% per protocol) of the 66 duodenal ulcer patients, but not in the other 25. The bacteria from 47 patients were genotyped. The only significant disease-associated difference in patterns observed was that the vacA m1 allele was represented more disproportionately among patients with eradication failures (68%) than in those with successful eradication (39%) (P < 0.05) No significant association of vacAs1 (signal sequence allele) or cag pathogenicity island status with persistence was detected. CONCLUSIONS: This study highlights the public health need for cheaper, more cost-effective anti-H. pylori therapies for developing countries, and suggests that subtle features of bacterial genotype can influence therapeutic efficiency. The possibility that particular vacA mid region alleles affect persistence, perhaps through toxin action on particular gastric cell types, merits further study.     

An evaluation of current shigellosis treatment

Shigellosis or bacillary dysentery, characterised by the passage of frequent loose stools mixed with blood and mucous, is caused by Shigella spp. which can be subdivided into four serotypes, namely, S. sonnei, S. boydii, S. flexneri and S. dysenteriae. S. dysenteriae type 1 produces severe dysentery and may be associated with many complications like leukaemoid reaction and haemolytic-ureamic syndrome. It is known to produce protracted epidemics and pandemics and is usually multi-drug resistant. Antibiotics are the mainstay of therapy of all cases of shigellosis. Antibiotics such as tetracycline, ampicillin and co-trimoxazole, were previously highly effective. Newer fluoroquinolones such as norfloxacin, ciprofloxacin, ofloxacin, azithromycin and ceftriaxone are effective. Although single dose of norfloxacin 800 mg and ciprofloxacin 1 g have been shown to be effective, they are currently less effective against S. dysenteriae type 1 infection. Oral rehydration salt should be given concurrently to prevent or correct dehydration. Antimotility agents are contraindicated. Feeding during and after shigellosis is emphasised. Hand-washing practices with plenty of water and soap help to prevent the transmission of infection from person to person. A search is on for an effective vaccine against shigella.     

Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention

Sulforaphane (SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapyregimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry.We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceuticalSFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.     

Does off-pump coronary artery bypass reduce the incidence of post-operative atrial fibrillation? A question revisited.

Atrial fibrillation (AF) is the most common post-operative complication in patients undergoing coronary artery bypass grafting, with an increased incidence associated with advancing age. This study aims to determine whether off-pump coronary artery bypass (OPCAB) reduces the incidence of AF in a generalized population (mean age <70 years). A meta-analysis was performed including all randomised and propensity score matched non-randomised studies published between 2001 and 2003 reporting a comparison between the two techniques in a generalised patient group (average age <70 years). The primary outcome of interest was post-operative AF. Sensitivity analysis was performed to evaluate consistency of the calculated treatment effect. Fourteen studies fulfilled our inclusion criteria, including a total of 16,505 subjects. The incidence of AF was 19% (1612/8265) in the off-pump group versus 24% (1976/8240) in the on-pump group. When considering only the 11 randomised studies (2207 subjects), we found a significant reduction in the incidence of post-operative AF in the off-pump group using a random-effect model (odds ratio (OR)=0.60, 95% confidence interval (CI)=0.45-0.82, and chi-square of heterogeneity=18.02, P=0.05). Sensitivity analysis highlighted one randomised study causing funnel plot asymmetry, exclusion of which resulted in a significant reduction in the incidence of post-operative AF in the off-pump group (OR=0.71, 95% CI=0.57-0.90), with a non-significant heterogeneity of 3.91 (P=0.92). When only studies of high quality were considered (898 patients), no significant difference was seen between on and off-pump groups (OR=0.78, 95% CI=0.57-1.07, and heterogeneity=0.53, P=0.91). This may be due to small number of patients in this group. Our results suggest that although OPCAB surgery may reduce the incidence of post-operative AF in a generalised population (age <70 years) this finding is not clearly supported by high quality randomised trials. Although previous evidence suggests that the incidence of post-operative AF is reduced in an elderly population (>70 years) with off-pump surgery, our results show that the evidence is less clear in a younger population group. The question of whether off-pump surgery in this patient group results in a lower rate of post-operative AF remains to be answered by further high quality randomised research.     

Use of verbal autopsy to determine mortality patterns in an urban slum in Kolkata, India

Objective

To define mortality patterns in an urban slum in Kolkata, India, in the context of a cholera and typhoid fever project.

Methods

In a well-defined population that was under surveillance for 18 months, we followed a dynamic cohort of 63 788 residents whose households were visited monthly by community health workers to identify deaths. Trained physicians performed verbal autopsies and experienced senior physicians assigned the primary cause of death according to the International classification of diseases, 10th edition. We tabulated causes of death in accordance with Global Burden of Disease 2000 categories and assessed overall and cause-specific mortality rates per age group and gender.

Findings

During 87 921 person–years of follow-up, we recorded 544 deaths. This gave an overall mortality rate of 6.2 per 1000 person–years. We assigned a cause to 89% (482/544) of the deaths. The leading causes of death, in descending order, were cardiovascular diseases (especially among adults aged over 40 years), cancer, respiratory ailments and digestive disorders. Most deaths in children under 5 years of age were caused by tuberculosis, respiratory infections and diarrhoeal diseases.

Conclusion

Although the most common causes of death in children were infectious, non-communicable diseases were predominant among adults. There is a need for continuing interventions against infectious diseases in addition to new and innovative strategies to combat non-infectious conditions.     

The extent of paternal sperm DNA damage influences early post-natal survival of first generation mouse offspring

Objectives

To study the post-natal characteristics and the survival of offspring derived from DNA damaged sperm.

Study design

This experimental prospective study was conducted on Swiss Albino mice (Mus musculus). Sperm DNA damage was induced by different doses of γ-irradiation in male mice who were then mated with healthy female mice. The post-natal characteristics including the survival of first generation offspring were studied and then correlated with the amount of paternal sperm DNA damage.

Results

A significant reduction of survival in the early post-natal period was observed in the first generation offspring derived from the DNA damaged sperm, and a strong association was observed between the extent of sperm DNA damage and the survival of the offspring.

Conclusion

The DNA damage load in sperm at the time of fertilization influences early post-natal survival of the mouse offspring.