Oseltamivir

Oseltamivir is the oral prodrug of GS4071, a selective inhibitor of influenza A and B viral neuraminidase. After absorption from the gastrointestinal tract oseltamivir is efficiently converted to GS4071, which is maintained at high and sustained concentrations in plasma. Based on studies in rats and ferrets, GS4071 appears to be effectively distributed to all tissues, including major sites of infection in the upper and lower respiratory tracts. Oral oseltamivir was an effective treatment in naturally occurring influenza when administered within 36 hours of symptom onset, reducing both the duration and severity of symptoms and the incidence of secondary complications in influenza-infected patients enrolled in 2 large placebo-controlled, double-blind trials. Prophylactic oral administration of oseltamivir was effective in reducing the incidence of influenza illness according to pooled data from 2 large placebo-controlled, double-blind trials of healthy nonimmunised volunteers during periods of seasonal influenza activity. The reported incidence of viral resistance to GS4071 was low in clinical isolates from oseltamivir treatment studies. All known GS4071 resistant genotypes are growth disadvantaged and display significantly reduced infectivity in animals. Oseltamivir was well tolerated in human volunteers and patients in clinical trials. Treatment-related adverse events (primarily gastrointestinal) were mild and transient in nature.     

Eptifibatide: a review of its use in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention

Eptifibatide, a cyclic peptide, is a highly specific, intravenously administered glycoprotein (GP) IIb/IIIa receptor antagonist. By preventing fibrinogen binding to the GP IIb/IIIa receptor, eptifibatide inhibits platelet aggregation and prevents thrombus formation. Clinically, the drug is used as an adjunct to heparin and aspirin. The PURSUIT trial, conducted in >10,000 patients with unstable angina or non-Q-wave myocardial infarction (MI), showed that eptifibatide (180 microg/kg bolus then 2 microg/kg/min infusion for < or =72 hours) reduces the 30-day risk of death or nonfatal MI, with this benefit apparent at 96 hours. The absolute reduction in this end-point of 1.5% persisted at 6 months. The drug is effective in patients undergoing percutaneous coronary intervention (PCI), and, as shown in the North American subgroup, in patients in whom medical management is appropriate. Eptifibatide is also beneficial in patients undergoing PCI, whether or not they have unstable angina or non-Q-wave MI. In a dosage of 135 microg/kg then 0.5 microg/kg/min for 24 hours, eptifibatide reduced the 30-day risk of a combined end-point (death, nonfatal MI and urgent or emergency coronary interventions) by 2.5% (absolute reduction) in patients undergoing PCI in the IMPACT-II trial, when measured by per-protocol (patients treated), but not intent-to-treat, analysis. The drug also decreased the incidence of abrupt vessel closure and ischaemic cardiovascular complications in the first 24 hours (the period of greatest risk). Bleeding episodes are the most common adverse event associated with eptifibatide therapy. Although the incidence of major bleeding is increased with eptifibatide, most bleeding episodes are minor and occur at the vascular access site. The drug is not associated with an excess of intracranial bleeds, stroke or thrombocytopenia, does not appear to increase bleeding risk in patients undergoing coronary artery bypass graft (CABG), and does not cause antibody formation. Limited data suggest that eptifibatide may improve coronary flow when combined with alteplase in patients with acute Q-wave MI, but the possibility of increased bleeding with eptifibatide plus thrombolytics should be borne in mind. CONCLUSIONS: Intravenous eptifibatide, when combined with aspirin and heparin, reduces the 30-day risk of ischaemic events in patients with unstable angina and non-Q-wave MI and decreases ischaemic cardiovascular complications at the time of greatest risk in patients undergoing PCI. With its acceptable tolerability profile eptifibatide is a suitable option as a short term adjunct in these clinical settings. Whether eptifibatide in combination with fibrolysis may improve outcome in patients with acute Q-wave MI has yet to be determined.     

OUTBREAK OF BANCROFTIAN FILARIASIS AMONG TROOPS AT AN ARMED FORCES STATION

A large number of microfilaria (MF) positive cases were reported at a Military Hospital in 1994. The epidemiological investigations included mass night blood survey, detection of sector breeding places and entomological studies. Control measures were instituted concurrently and this included treatment of positive cases, sector control measures, personal protection and health education. The mass blood survey was continued in 1995 as well to find the outcome of control measures. A total of 215 MF positive cases were detected in 1994 with MF rate of 9.63. The only MF species identified was Wuchereria bancrofti. 203% cases were in the station for less than six months. 71.3% of MF positive cases were asymptomatic. As per state health authorities, Culex quinquefasciatus was the known vector for spread of the disease in the region. However, in present study, it could not be implicated as dissection of over 200 mosquitoes of this species was negative for filarial parasite. Our study stresses the importance of close monitoring of the disease by night blood surveys and effective integrated vector control measures.KEY WORDS: Control, Epidemiology, Filariasis     

Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects

Spontaneous mutation rates at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were measured in human cancer cell lines defective in the mismatch repair (MMR) genes hMLH1, hPMS2, or GTBP, as well as in a cell line carrying mutations in both hMLH1 and hPMS2. The mutation rate was determined by quantitating mutant frequency increases within a single culture as a function of cell division. These MMR- deficient cell lines exhibited a 50- to 750-fold increase in mutation rate relative to a MMR-proficient cancer cell line. From lowest to highest, the spontaneous mutation rates relative to the MMR-gene defects studied here are as follows: hMLH1- < GTBP- < hPMS2- < hMLH1- / hPMS2-. In addition, a cell line in which MMR was restored by chromosome transfer exhibited a mutation rate 12-fold below the MMR- deficient parental cell line. These data support the notion that MMR plays an important role in controlling the rate of spontaneous mutation and suggest that different MMR-gene defects may vary in their ability to repair different types of DNA mismatches, thus leading to measurable quantitative differences in spontaneous mutagenesis. Furthermore, a difference in mutation rates was observed between a hPMS2-defective cell line (3.1 x 10(-5) mutations/cell/generation) and two hMLH1- defective cell lines (4.0 x 10(-6) and 7.3 x 10(-6) mutations/cell/generation). Assuming the hPMS2- and hMLH1-gene products only function in the proposed hMutL alpha heterodimer, then defects in either gene should yield comparable mutation rates. These data suggest that hPMS2 plays a critical role in MMR, while additional hMLH1 homologues or hPMS2 alone may function to partially complement defects in hMLH1.      

Stent placement in coeliac and superior mesenteric arteries to restore vascular perfusion following aortic dissection

The main trunks of both coeliac and superior mesenteric arteries were sheared off the abdominal aorta by an anterior dissection that spared the renal arteries. Both vessels were cannulated and a Walstent inserted across the false lumen to restore normal coeliac and superior mesenteric perfusion. This produced a successful haemodynamic and angiographic result with improvement in the patient's clinical condition.     

Long term effects of early nutritional support with new enterotropic peptide-based formula vs. standard enteral formula in HIV-infected patients: randomised prospective trial Chlebowski R T, Beall G, Grovenor M, Lillington L, Weintraub N, Ambler C, Richards E W, Abbruzzese B C, McCamish M A and Cope F O Nutrition 1993; 9 (6): 507-512

This paper describes a prospective trial of a new peptide based formula (NEF) compared with a standard enteral formula (SEF) in the management of weight loss in people with HIV infection. 80 largely asymptomatic patients were randomised to receive 2-3 8 oz cans of either the NEF or SEF supplement. Outcome measures included adherence, weight change, anthropometric measurements, serum biochemistry, gastrointestinal symptoms, physical performance and intercurrent health events and were assessed at baseline, 3 and 6 month intervals. For the 56 evaluable patients those receiving the NEF supplement maintained body weight better (p = 0.04), had more stable triceps skinfold measurements (p = 0.03), lower blood urea nitrogen (p = 0.04), and reduced hospitalisation during the 3-6 month evaluation period (p = 0.02) than those consuming the SEF supplement. The NEF supplement was well tolerated and did not result in untoward clinical effects. These data suggest that the supplemental use of a NEF provides superior nutritional management compared to an SEF for patients with early stage HIV infection.