Type-specific serological testing for herpes simplex infection

The effects of reactive oxygen species (ROS) on elastin molecules (tropoelastin) were studied in vitro. ROS generated by ultraviolet A and hematoporphyrin rapidly degraded tropoelastin within 5 min. Their degradative activity was inhibited by the addition of NaN3. Treatment of tropoelastin with copper sulfate/ascorbic acid resulted in degradation of tropoelastin producing fragments of molecular weight 45, 30 and 10 kDa within 30 min. The degradation of tropoelastin was partially blocked by the addition of mannitol. ROS induced by the xanthine/xanthine oxidase system also degraded tropoelastin within 6 h. The degradation was blocked by catalase but not by superoxide dismutase (SOD). ROS generated by copper-ascorbate seems to be unique in that it cleaves relatively specific sites of the tropoelastin molecule. Thus ROS may play a degradative role in elastin metabolism which may cause the elastolytic changes or the deposition of fragmented elastic fibers in photoaged skin or age-related elastolytic disorders.     

Apoptosis and related proteins in different stages of human atherosclerotic plaques

BACKGROUND: The transition of a fatty streak into an atherosclerotic plaque is characterized by the appearance of focal and diffuse regions of cell death. We have investigated the distribution of apoptotic cell death and apoptosis-related proteins in early and advanced atherosclerotic lesions. METHODS AND RESULTS: Human atherosclerotic plaques were studied by whole-mount carotid endarterectomy specimens (n=18). This approach allowed comparison of adaptive intimal thickenings, fatty streaks, and advanced atherosclerotic plaques of the same patient. The fatty streaks differed from adaptive intimal thickenings by the presence of BAX (P<0.01), a proapoptotic protein of the BCL-2 family. Both regions were composed mainly of smooth muscle cells (SMCs), and macrophage infiltration was low and not different. Apoptosis, as detected by DNA in situ end labeling (terminal deoxynucleotidyl transferase end labeling [TUNEL] and in situ nick translation) was not present in these regions. Apoptosis of SMCs and macrophages, however, was present in advanced atherosclerotic plaques that were present mainly in the carotid sinus. A dense infiltration of macrophages (5.8+/-3% surface area) was present in these advanced atherosclerotic plaques. Cytoplasmic remnants of apoptotic SMCs, enclosed by a cage of thickened basal lamina, were TUNEL negative and remained present in the plaques as matrix vesicles. CONCLUSIONS: We conclude that SMCs within human fatty streaks express BAX, which increases the susceptibility of these cells to undergo apoptosis. The localization of these susceptible SMCs in the deep layer of the fatty streaks could be important in our understanding of the transition of fatty streaks into atherosclerotic plaques, which are characterized by regions of cell death. Matrix vesicles are BAX-immunoreactive cytoplasmic remnants of fragmented SMCs that can calcify and may be considered the graves of SMCs that have died in the plaques.     

Implementation of the Ottawa ankle rules in France. A multicenter randomized controlled trial

OBJECTIVES: To assess the impact of the implementation of the Ottawa ankle rules on radiography requests in French hospitals during a 5-month intervention period and the impact of using posters alone to sustain the effect of the rules during a 5-month postintervention period. DESIGN: Multicenter randomized controlled trial preceded and followed by observational studies of radiological practices. SETTING: The emergency departments of 5 Paris university teaching hospitals of the Assistance Publique-H?pitaux de Paris. PATIENTS: A total of 2218, 1911, and 851 patients-all aged 18 years and older-who were seen for acute ankle or midfoot injuries in emergency departments during preintervention, intervention, and postintervention periods, respectively. INTERVENTION: Implementation of the Ottawa ankle rules by emergency department physicians in the intervention hospitals (using meetings, posters, pocket cards, and data forms). During the postintervention period, posters alone were used to sustain the intervention effect. MAIN OUTCOME MEASURE: Percentage of patients for whom radiography was requested. RESULTS: During the preintervention period, 98% and 98.5% of patients were referred for radiography in the intervention and control groups, respectively. During the intervention period, the mean proportions of patients referred for radiography by physicians was 78.9% in the intervention group and 99% in the control group (P=.03). Between preintervention and intervention periods, a relative reduction of 22.4% (95% confidence interval [CI], 19.8%-24.9%) in radiography requests was observed in the intervention group, while requests increased by 0.5% (95% CI, 0%-1.4%) in the control group. During the postintervention period, the proportion of radiography requests in the intervention hospitals was lower than the proportion observed in the preintervention period (83.1% vs 98%). CONCLUSIONS: Implementation of the Ottawa ankle rules significantly reduced radiography requests in French hospitals. Using a minimal postintervention implementation strategy, the effect of this intervention decreased but persisted after it was discontinued.     

Orally active inhibitors of human leukocyte elastase. II. Disposition of L-694,458 in rats and rhesus monkeys

The disposition of L-694,458, a potent monocyclic beta-lactam inhibitor of human leukocyte elastase, was studied in male Sprague-Dawley rats and rhesus monkeys. After iv dosing, L-694,458 exhibited similar pharmacokinetic parameters in rats and rhesus monkeys. The mean values for its plasma clearance, terminal half-life, and volume of distribution at steady state were 27 ml/min/kg, 1.8 hr, and 4.0 liters/kg in rats and 34 ml/min/kg, 2.3 hr, and 5 liters/kg in rhesus monkeys. The bioavailability of a 10 mg/kg oral dose was higher in rats (65%) than in rhesus monkeys (39%). In both species, concentrations of L-694,458 in plasma increased more than proportionally when the oral dose was increased from 10 mg/kg to 40 mg/kg. In monkeys a protracted plasma concentration-time profile was observed at 40 mg/kg, characterized by a delayed T(max) (8-24 hr) and a long terminal half-life (6 hr). [3H]L-694,458 was well absorbed after oral dosing to rats at 10 mg/kg, as indicated by the high recovery of radioactivity in bile (83%) and urine (6%) of bile duct-cannulated rats. Only approximately 5% or less of the radioactivity in bile, urine, and feces was a result of intact L-694,458, indicating that the compound was being eliminated by metabolism, followed by excretion of the metabolites in feces, via bile. Demethylenation of the methylenedioxyphenyl group resulting in the catechol was the primary metabolic pathway in human and rhesus monkey liver microsomes. In rat liver microsomes, the major metabolite was the N-oxide of the methyl-substituted piperazine nitrogen. In rats dosed iv and orally with [3H]L-694,458, concentrations of radioactivity were highest in the lung (the primary target tissue), adrenals, and liver. L-694,458 was unstable in rat blood and plasma, degrading via a pathway believed to be catalyzed by B-esterases and to involve cleavage of the beta-lactam ring and loss of the methylpiperazine phenoxy group. In vitro studies indicated that in human liver, L-694,458 was metabolized by CYP3A and 2C isozymes, and in both monkey and human liver microsomes the compound acted as an inhibitor of testosterone 6beta-hydroxylation.     

Management of splenic trauma at a rural, Level I trauma center

The spleen is the most commonly injured organ in blunt abdominal trauma. There remains much controversy in the diagnosis and management of the injured spleen, with a recent trend toward nonoperative management. A 5-year period was reviewed at a rural, Level I trauma center to address issues of operative versus nonoperative management. During this time period, there were 136 patients identified as having trauma to the spleen. Most (95%) were the result of blunt trauma, and a majority of these were from motor vehicle accidents. Computed tomography was the most frequent method of diagnosis. Approximately half of the patients underwent immediate operative intervention. Of those initially observed, 10 patients (16%) eventually were operated on. Most of the cases were due to underestimation of the severity of the splenic injury, and most received blood transfusion. This experience suggests that observation for splenic trauma is appropriate in many cases, as long as the surgeon is certain the spleen is not actively bleeding and the patient will not require blood transfusion.     

Haemoptysis associated with pulmonary varices: demonstration using computed tomographic angiography

A 67 yr old female with mitral stenosis presented with an acute haemoptysis caused by the rupture of pulmonary varices. Chest radiography and bronchoscopy showed nonspecific abnormalities. The diagnosis of this rare but potentially lethal complication was made using computed tomographic angiography with three-dimensional volume rendering.