The Prevalence of P. malariae in Odisha, India.

Odisha, an eastern Indian state, is known to be highly endemic for malaria. The current national malaria control programme uses rapid diagnostic test (RDT) for early diagnosis and prompt treatment of the cases followed by microscopy for the identification of species. But as per the available literatures and from our own experience it is known that microscopy suffers with underestimation of mixed Plasmodium species infection, especially P. malariae and P. ovale. Since PCR has proven to have more sensitivity and specificity and able to detect multiple infection of Plasmodium species, we have made an attempt to find out the prevalence of species of parasites by PCR and compare the results with light microscopy. During this study 1589 individuals presenting with fever from two malaria endemic blocks namely Badampahar and Ghatgaon were investigated. Amongst them 110 cases were found to be PCR positive while 99 were microscopically positive for malaria. Out of the total PCR positive cases 42 cases (38.2%) had P. falciparum, 35 (31.8%) had P. vivax and 10 (9.1%) had P. malariae mono infections, while 23 (20.9 %) cases had mixed infections. Of the total 23 mixed infections 11(10%) were having P. falciparum plus P. vivax and rest 12 (10.9%) cases were having P. malariae mixed with either P. falciparum and /or P. vivax. However microscopically only 1(1.4%) case was found to have P. malariae mono infection and none of the mixed infections harbor P. malariae. Multiple kind lottery model analysis of PCR positive samples demonstrated that P. malariae is not distributed randomly in population when compared by different age groups, gender and season. The study also has shown that PCR is highly effective in screening the severe and asymptomatic malaria cases than LM. The result of this study warrants newer surveillance strategies for case detection and management by the programme.

Successful combined heart-bilateral lung-kidney transplantation from a same donor to treat severe hypertrophic cardiomyopathy with secondary pulmonary hypertension and renal failure: case report and review of the literature.

This study describes the first reported case of a combined heart-lung-kidney transplantation. Our patient suffered from hypertrophic cardiomyopathy due to long-standing hypertension with Dana Point Classification Group 2 pulmonary hypertension from the underlying cardiac disease, along with renal failure necessitating renal replacement therapy. Twenty months after the transplant procedure, she has stable pulmonary and renal function, plus has resumed a normal daily life with improving exercise tolerance. We propose that a combined heart-lung-kidney transplantation may be an acceptable therapeutic option for carefully selected patients with advanced, concomitant cardiac, pulmonary, and kidney disease.

Sexual behaviour and condom use among individuals with a history of symptomatic genital herpes.

OBJECTIVES: This study describes the differences in sexual behaviour in individuals with genital herpes (GH) during "symptomatic" and "asymptomatic" periods of the disease. METHODS: A cross sectional questionnaire was undertaken by 1193 individuals attending clinics between 1998 and 2001. All participants in this analysis were in heterosexual, monogamous partnerships, self identified with a history of symptomatic GH and with confirmed HSV-2 infection. RESULTS: Sexual activity reported during asymptomatic v symptomatic periods of GH was 98% v 40% (p<0.001), 76% v 29% (p<0.001), and 25% v 11% (p<0.001) for vaginal, oral, and anal intercourse, respectively, while "always" condom use during asymptomatic and symptomatic periods was 20% v 35% (p<0.001), 2% v 7% (p<0.001), and 10% v 15% (p = 0.131), respectively. The proportion of individuals who either abstained from vaginal intercourse or "always" used condoms was 21% v 74% (p<0.001), for asymptomatic v symptomatic periods. Multivariable analyses indicated that factors associated with engaging in intercourse during symptomatic periods of GH included current intrauterine device use (adjusted odds ratio (aOR) = 2.96, 95% confidence interval (CI) = 1.46 to 6.02); living in Latin America (aOR = 2.16, CI = 1.19 to 3.91) or Europe (aOR = 1.67, CI = 1.21 to 2.28), compared with North America; previous sexually transmitted disease (aOR = 1.42, CI = 1.08 to 1.89); a higher number of sexual acts per month (aOR = 1.09, CI = 1.06 to 1.11); and a higher number of GH recurrences per year (aOR = 1.08, CI = 1.03 to 1.12). CONCLUSIONS: These data indicate that the majority of people with GH either abstained from intercourse or "always" used condoms during symptomatic periods of GH. However, condom use was relatively low during asymptomatic periods in comparison with symptomatic periods. These results highlight that further education on GH prevention is warranted, particularly for symptomatic periods.

Lyophilized formulations of recombinant tumor necrosis factor.

Recombinant tumor necrosis factor-alpha (TNF), an investigational biological response modifier, is a protein and is susceptible to particulate generation during handling in dilute aqueous solutions. TNF is prone to formation of nonreducible dimers and oligomers during formulation, lyophilization, and storage. The effect of various parameters, such as the pH, protein concentration, and nature of excipients present during lyophilization, on the formation of nonreducible dimers and oligomers was investigated. The results of these studies indicate that these parameters can significantly alter the rate of this reaction. Inclusion of an amorphous buffer and an appropriate amount of a crystallizing sugar (mannitol) combined with a suitable quantity of an amorphous protectant (dextran, sucrose, trehalose, or 2-hydroxypropyl-beta-cyclodextrin) was shown to reduce the formation of these dimeric and oligomeric species during lyophilization. Representative lyophilized formulations of TNF based on selected amorphous excipients were found to be fully bioactive and stable over 9 months.

Development of a lyophilized formulation of interleukin-2.

Native human interleukin-2 (IL-2) comprises a group of glycoproteins of MW 13,000-17,500. Recombinant human IL-2 (rhIL-2) (Cetus) is derived from E. coli and is not glycosylated. We have evaluated several processes for manufacturing rhIL-2, based on different chaotropic agents for solubilization of insoluble protein pastes. Formulation work carried out with material purified by one of these processes is reported here. Our studies have indicated that the presence of a stabilizer in the form of an amorphous excipient, such as amino acids, a non-ionic surfactant (polysorbate 80), hydroxypropyl-beta-cyclodextrin or human serum albumin was essential for preservation of rhIL-2 during lyophilization. Each of these formulations exhibited its own unique problems. We have overcome these problems through a systematic formulation development program and have been successful in developing several lyophilized formulations of rhIL-2 with optimum properties and performance.

Release of human serum albumin from poly(lactide-co-glycolide) microspheres.

Human serum albumin (HSA) was encapsulated in a 50:50 copolymer of DL-lactide/glycolide in the form of microspheres. These microspheres were used as a model formulation to study the feasibility of controlling the release of large proteins over a 20- to 30-day period. We show that HSA can be successfully incorporated into microspheres and released intact from these microspheres into various buffer systems at 37 degrees C. A continuous release of the protein could be achieved in physiological buffers at 37 degrees C over a 20- to 30-day period from microspheres with high protein loadings (11.6%). These results demonstrate the potential of poly(DL-lactide-co-glycolide) microspheres for continuous delivery of large proteins.

Controlled release of interleukin-2 from biodegradable microspheres.

We have evaluated the use of biodegradable poly(DL-lactide-co-glycolide) microspheres for the controlled release of interleukin-2 (IL-2) and its modified forms: succinyl IL-2 (SIL-2) and polyethylene glycol-modified IL-2 (PEG IL-2). We show that a microsphere formulation can be prepared from PEG IL-2 using HSA as an excipient which, after an initial burst, releases 2-3% PEG IL-2 per day in a bioactive form continuously over a 20- to 30-day period.

The role of context in the perception of orientation by the rat.

Two experiments are reported which demonstrate the role of contextual factors in the rat's perception of orientation. Designed to eschew criticisms of an earlier study by McGonigle and Jones, the first experiment shows that the rat's perception of linear Gestalten is conditional upon the set of alternative patterns within which the (linear) pattern is embedded. The second experiment shows that the ecological framework of an orientational cue (rather than its position relative to retinocortical coordinates) determines the rat's perception of vertical and horizontal stimuli.