Necrotizing soft-tissue infections.

Necrotizing soft-tissue infections have been widely recognized for over a century, but they remain a challenging problem in clinical infectious disease. Patterns of disease are clearly apparent, but most are polymicrobial and derive increased virulence from synergy between bacteria. Early recognition and prompt surgical drainage are the keys to successful treatment. Edema extending beyond the area of erythema, skin vesicles, crepitus or air in the subcutaneous tissues, and absence of lymphangitis and lymphadenitis are markers of necrotizing infections, particularly when they occur in patients with serious underlying disease. Empiric broad-spectrum antibiotics, prophylactic heparin, and nutritional therapy are important adjuncts to aggressive "stepwise" surgical debridement. A knowledge of patterns of disease can aid in fine-tuning treatment to decrease morbidity.     

Brain neurotransmitter changes in human narcolepsy.

We measured the concentrations of the three major monoamine neurotransmitters noradrenaline, dopamine, and serotonin, their metabolites, and receptor binding sites in autopsied brain of three patients with narcolepsy. As compared with the controls, concentrations of the noradrenaline and serotonin metabolites MHPG and 5-HIAA, respectively, were markedly elevated in cerebral cortical subdivisions of the narcolepsy patients together with a trend for above-normal neurotransmitter/metabolite "turnover" ratio. A moderately reduced number of alpha 1-adrenoceptors, as judged by the reduced levels of 3H-prazosin binding, was observed in cerebral cortex of two of the three patients with narcolepsy. Mean striatal levels of dopamine and its metabolite homovanillic acid were normal, whereas the concentration of dopamine's second metabolite, dihydroxyphenylacetic acid, was markedly reduced by 50% or greater. This was accompanied by a marked increase (+125%) in mean 3H-spiperone binding to the D2 dopamine receptor in both caudate and putamen; in contrast, the levels of 3H-SCH 23390 binding to the striatal D1 dopamine receptor were in the normal range. Our data provide evidence for altered brain monoaminergic neurotransmitter function in human narcolepsy.     

The restoration of improperly inclined osseointegrated implants

Improper implant angulation is one of the most difficult problems to overcome in the fabrication of implant-supported and implant-retained restorations. Several techniques using the "UCLA" abutment have been developed to solve these problems. The creation of large screw-access holes for moderate angulation and the fabrication of telescopic copings and overlay castings for severe angulation problems are discussed.     

Evidence for a neural basis of age-related visual field loss in normal observers

Many studies have reported a decrease in visual field sensitivity as a function of increasing age in normal individuals. This age-related sensitivity loss has mainly been attributed to reductions in pupil size and transmission losses of the ocular media (particularly the lens), although neural losses in the retina, optic nerve and visual cortex have also been suggested. We evaluated the role of preretinal factors on normal visual field changes associated with aging. The central visual field of both eyes of 62 normal subjects (ages 20 to 72) were evaluated with Program 30-2 of a modified Humphrey Field Analyzer. Three test procedures were employed: (1) a standard visual field evaluation; (2) a yellow target on a yellow background condition (530 nm cutoff filter) to minimize the influence of lens transmission losses with age; and (3) a large target/high background luminance "yellow on yellow" test condition (530 nm cutoff filter, 635 asb background, Size V target) to minimize both pupil size and lens effects on central visual field sensitivity. In addition, relative lens absorption estimates were obtained for each subject. All three test conditions revealed a loss in visual field sensitivity with increasing age (approximately 0.8 dB per decade) but no meaningful differences were found among the three test procedures. Relative lens density increased with age but was not related to visual field sensitivity for any of the three test conditions. These data suggest that normal age-related visual field sensitivity changes are primarily due to neural losses rather than preretinal factors.     

Acute intracerebroventricular injections of the mast cell degranulator compound 48/80 and behavior in rats

The intracerebroventricular (ICV) injection of the mast cell degranulator Compound 48/80 (2.5-2.0 micrograms/kg) produced a marked behavioral syndrome in normotensive rats. The behaviors included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, and a later phase of sedation. The highest doses (15 and 20 micrograms/kg) also produced catalepsy and episodes of "barrel rolling" (continuous rolling of 1-8 turns around the longitudinal axis). These behaviors were observed for approximately 15-30 min although the sedation and catalepsy were maintained for 90-120 min. A second ICV injection of the 10 micrograms/kg dose of Compound 48/80 given 2 hr after an initial injection of this dose, produced a much reduced response and the numbers of head and body shakes, and episodes of paw tremor and grooming were between 20-30% of those produced by the first injection. The reduced effect of the second injection indicates that the behavioral effects of Compound 48/80 may arise from the acute degranulation of mast cells rather than direct effects on neuronal populations or the cerebral vasculature.     

Synthesis of stereospecifically deuterated desoxypodophyllotoxins and 1H-nmr assignment of desoxypodophyllotoxin

[4 beta- 2H1]Desoxypodophyllotoxin [3], [4 alpha- 2H1]desoxypodophyllotoxin [4], and [4, 4- 2 H2]desoxypodophyllotoxin [9] were prepared from podophyllotoxin [1] via its chloride [5]. A complete assignment of the 1H-nmr spectrum of desoxypodophyllotoxin [2] was made on the basis of the spectra of the deuterated compounds [3] and [4].     

Neutrophil responses to platelet-activating factor

1-O-Alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (i.e., platelet-activating factor) was prepared and confirmed to possess potent platelet aggregating activity. It was also potent in aggregating and degranulating rabbit and human neutrophils. When injected into rabbits, the lipid induced profound neutropenia, thrombocytopenia, and anaphylactic symptoms. The lyso derivative of this lipid, 1-O-alkyl-sn-glyceryl-3-phosphorylcholine, was inactive or several orders of magnitude weaker in inducing these responses. The acetylated lipid appears to be a potent stimulator of both platelets and neutrophils. Its anaphylactic-like toxicity may be related, at least in part, to its ability to aggregate or otherwise stimulate these cells.This work was supported by NIH grants AI09169, AI10732, AI14929, HL16769, HL14164, and AMI1799.