Non-peptidic HIV protease inhibitors: C2-symmetry-based design of bis-sulfonamide dihydropyrones

Potent, non-peptidic, dihydropyrone sulfonamide HIV protease inhibitors have been previously described. Crystallographic analysis of dihydropyrone sulfonamide inhibitor/HIV protease complexes suggested incorporation of a second, C2 symmetry-related sulfonamide group. Selected bis-sulfonamide dihydropyrone analogues display high HIV protease inhibitory activity.     

Meshlaparostomy--a comparison between polypropylene mesh and indigenous nylon net

Polypropylene mesh, the routinely used material for mesh laparostomies is expensive. A economical and easily available substitute-nylon net was compared with polypropylene mesh with regard to efficacy and wound complications in a retrospective study. 51 patients, 25 in the polypropylene mesh group and 26 in the nylon net group were studied. The groups were matched with respect to age, sex, indication for surgery and mortality. The mean hospital stay (65 vs 54 days), fate of the wound, incidence of mesh extrusion (26% vs 20%), bowel perforation (1 vs none) and incisional hernia formation (21% vs 20%) in those with polypropylene mesh and nylon net respectively was similar. In conclusion, nylon net is an effective and inexpensive indigenous substitute for polypropylene mesh for mesh laparostomies.     

Transmission-based scatter correction of 180 degrees myocardial single-photon emission tomographic studies

Meaningful comparison of single-photon emission tomographic (SPET) reconstructions for data acquired over 180 degrees or 360 degrees can only be performed if both attenuation and scatter correction are applied. Convolution subtraction has appeal as a practical method for scatter correction; however, it is limited to data acquired over 360 degrees. A new algorithm is proposed which can be applied equally well to data acquired over 180 degrees or 360 degrees. The method involves estimating scatter based on knowledge of reconstructed transmission data in combination with a reconstructed estimate of the activity distribution, obtained using attenuation correction with broad beam attenuation coefficients. Processing is implemented for planes of activity parallel to the projection images for which a simplified model for the scatter distribution may be applied, based on the measured attenuation. The appropriate broad beam (effective) attenuation coefficients were determined by considering the scatter buildup equation. It was demonstrated that narrow beam attenuation coefficients should be scaled by 0.75 and 0.65 to provide broad beam attenuation coefficients for technetium-99m and thallium-201 respectively. Using a thorax phantom, quantitative accuracy of the new algorithm was compared with conventional transmission-based convolution subtraction (TDCS) for 360 degrees data. Similar heart to lung contrasts were achieved and correction of 180 degrees data yielded a 10.4% error for cardiac activity compared to 5.2% for TDCS. Contrast for myocardium to ventricular cavity was similarly good for scatter-corrected 180 degrees and 360 degrees data, in contrast to attenuation-corrected data, where contrast was significantly reduced. The new algorithm provides a practical method for correction of scatter applicable to 180 degrees myocardial SPET.     

Premature separation of centromere and aneuploidy: an indicator of high risk in unaffected individuals from familial breast cancer families?

OBJECTIVES: Injury is the leading cause of death in the male working population of Brazil. An important fraction of these deaths are work related. Very few cohort studies of steel workers, and none from developing countries, have reported on mortality from injuries. This paper analyses mortality from work and non-work related injuries among Brazilian steel workers. METHODS: Deaths during employment from 1 January 1977 to 30 November 1992 were analysed in a cohort of 21,816 male steel workers. Mortality rates specific for age and calendar year among the workers were compared with those of the male population of the state where the plant is located. Work related injuries were analysed by comparing the mortality rates for different subgroups of the cohort. RESULTS: The number of deaths (391) was less than half that expected based on death rates of the general population. Over 60% (242) of deaths were due to injuries. Mortality from most causes was substantially below that in the general population, but that from unintentional injury, was 50% above that of the general population. Standardised mortality ratios (SMRs) were highest for the youngest and the oldest employees and for labourers and clerical workers. Mortality from motor vehicle injury was twice that expected from population rates (SMR = 209, 95% confidence interval (95% CI) 176-244). There was a 67% fall in the age adjusted mortality from occupational injuries in the study period. CONCLUSION: The healthy worker effect in this cohort was greater than that commonly found in studies of occupational groups in developed countries, probably because of a greater socioeconomic gap between employed and unemployed populations in Brazil, and unequal distribution of health care resources. Mortality was especially high for motor vehicle injuries. The fall in mortality from occupational injuries during the study period was probably due to improvement in safety standards, increased automation, and better medical care. There is a need to investigate risk factors for unintentional injuries among steel workers, especially those due to motor vehicle injuries. Prevention of occupational and nonoccupational injuries should be a main priority in Brazil.     

The community-centered board model of managed care for people with developmental disabilities

An asymmetric triazine derivative, HOE 092 V,2-[3,5-alpha-dichloro-4-(4-methyl-sulfonylphenoxy)-phenyl]- 1-methyl-hexahydro-1,2,4-triazine-3,5-dion, was tested in vivo against Glugea anomala parasitizing the connective tissue of sticklebacks (Gasterosteus aculeatus). Naturally infected sticklebacks were incubated in 10-1 plastic aquaria in water containing 0, 2.5, 5, and 10 micrograms HOE 092 V/ml for 2, 3, and 4 h at 22 degrees C. As seen at the ultrastructural level, the drug caused severe damage to all developmental stages of G. anomala except the mature spores. Starting with a dose of 2.5 micrograms/ml, the drug caused significant damage on uni- and multinucleate meronts, sporogonial plasmodia, and sporoblasts. The damage mainly consisted in a decrease in the number of ribosomes, an enlargement of the smooth endoplasmic reticulum and a vacuolization of the cytoplasma. When treatment was done with 5 micrograms for 2 h, multinucleate meronts and sporogonial plasmodia were no longer detectable, and the sporoblasts and the prespore stages except the mature spores had shrunk. After incubation of the infected fish with 10 micrograms HOE 092 V/ml and 4 h exposure, uninucleate meronts were no longer detectable by means of transmission electron microscopy. In the sporoblast mother cells, vacuolization of the cytoplasma and lysis of the nuclei occurred. However, mature spores were not affected. It seems likely that HOE 092 V can be successfully applied in medicinal baths against Microsporidia in fish. The infected fish should be incubated in separate, aerated containers.     

Ultrastructural immunocytochemical localization of neurotensin and the dopamine D2 receptor in the rat nucleus accumbens

The neuroleptic-like effects of neurotensin (NT) are thought to be due to interactions with dopamine (DA) acting primarily at D2 receptors within the nucleus accumbens septi (Acb). Using electron microscopic dual labeling immunocytochemistry, we sought to demonstrate cellular substrates for functional interactions involving NT and DA D2 receptors in the adult rat Acb. Peroxidase reaction product representing D2 receptor-like immunoreactivity (D2-LI) was seen along membranes of Golgi lamellae and multivesicular bodies of perikarya containing immunogold labeling representing NT-LI. Dually labeled somata usually contained highly indented nuclei, a characteristic of aspiny neurons. Dendrites also occasionally colocalized the two immunomarkers. Other somata, dendrites, and all axon terminals were singly labeled with either NT-LI or D2-LI. In distinct sets of terminals, NT-LI was commonly associated with large, dense-cored vesicles, whereas D2-LI was found along the plasmalemma and over nearby small clear vesicles. Each type of terminal comprised approximately 20% of synaptic input to NT-immunoreactive dendrites. Similar proportions of terminals containing NT-LI or D2-LI contacted unlabeled (approximately 55%) or NT-labeled (approximately 35%) dendrites and, occasionally, were observed converging onto common dendrites. Terminals containing NT-LI or D2-LI also were often closely apposed. These findings provide the first ultrastructural evidence that: (1) NT and D2 receptors are colocalized in aspiny neurons and dendrites, (2) NT may produce a direct postsynaptic effect on neurons receiving input from terminals which are presynaptically modulated by DA via D2 receptors, and (3) NT and DA acting at D2 receptors may interact through presynaptic modulation of common axon terminals.