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Biomedical subjects

M Caplan

Publications and source records attributed to M Caplan.

At least 19 recordsLinked to original sources

The mediastinum--is it wide?

OBJECTIVE: To determine if the 8 cm upper limit for mediastinal width applies in the trauma setting of today. To define the upper limit of normal mediastinal width for supine chest films. METHODS: A retrospective review of chest computed tomography scans was conducted to determine the width and position of the mediastinum within the supine chest. Radiographs were performed using a model that enabled the degree of mediastinal magnification to be ascertained in a variety of clinical settings. RESULTS: The mean mediastinal width is 6.31 cm. With standard radiographical techniques this mediastinum is magnified to 8.93-10.07 cm. With minor adaptations in radiographical technique this can be reduced to 7.31-7.92 cm. CONCLUSION: The 8 cm upper limit for normal mediastinal width, set in the 1970s does not apply in the modern trauma room. Changes in the position of the x ray cassette, and lengthening of the distance between the patient and the x ray source will significantly reduce magnification. A new range of upper limits is defined for the radiographical techniques possible in different trauma settings.

Humans↗

Platelet-activating factor increases mucosal permeability in rat intestine via tyrosine phosphorylation of E-cadherin.

1. Platelet-activating factor (PAF), an inflammatory mediator, plays an important role in mediating intestinal injury. However, it remains unclear whether PAF has a function in the intestine. The production of PAF by normal intestine and by unstimulated intestinal epithelial cell lines suggests that PAF may have a regulatory function in the normal bowel. 2. In this study we investigated the role of PAF in modulating intestinal mucosal permeability in rats. Lumen-to-blood transit of FD-4 (dextran 4400), (an index of intestinal permeability), was assessed in sham-operated rats and rats injected with PAF (1.25 microg kg(-1), i.v., a dose insufficient to induce intestinal injury). 3. PAF-induced villus cytoskeletal changes were examined by staining the intestine for F-actin. The effect of PAF on tyrosine phosphorylation of the junctional protein E-cadherin was examined by immunoprecipitation. Some rats were pretreated with AG1288 (a tyrosine kinase inhibitor) before PAF injection, and mucosal permeability change was assessed. 4. To investigate the role of endogenous PAF upon mucosal permeability, we studied the effect of PAF antagonists on (intraluminal) glucose-induced increase in mucosal permeability. 5. We found that low dose PAF: (a) alters the cytoskeletal structure of intestinal epithelium, (b) causes the influx of FD4 from intestinal lumen to systemic circulation, (c) induces tyrosine phosphorylation of E-cadherin and cadherin-associated proteins. Glucose-induced mucosal permeability increase is abolished by using two structurally different PAF antagonists. 6. These results suggest that endogenous PAF modulates macromolecular movement across the intestinal mucosal barrier, probably via tyrosine phosphorylation of E-cadherin and cytoskeletal alteration of enterocytes.

Animals↗

High-power electrostatic free-electron maser as a future source for fusion plasma heating: experiments in the short-pulse regime.

A high-power, frequency-tunable electrostatic free-electron maser, being developed at the FOM Institute for Plasma Physics "Rijnhuizen," shows lasing at various frequencies. An output power of 730 kW at 206 GHz is generated by a 7.2-A, 1.77-MeV electron beam, and 380 kW at 165 GHz is generated by a 7.4-A, 1.65-MeV electron beam. In the present experimental setup, without recovery of the spent electron beam power, the pulse length is limited to 12 micros. Nevertheless, the main issues, such as the possibility of high-power, single-mode operation and frequency tuning, have been confirmed. The experimental results and the dynamics of the laser process are well in accordance with simulations.

Journal Article↗

Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

OBJECTIVE: To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. MATERIALS AND METHODS: Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. RESULTS: Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. CONCLUSION: Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma.

Autopsy↗

Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.

BACKGROUND: Myocardial ischemia increases heart glucose utilization in vivo. However, whether low-flow ischemia leads to the translocation of glucose transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown. METHODS AND RESULTS: In a canine model, we evaluated myocardial glucose metabolism in vivo and the distribution of GLUT-4 and GLUT-1 by use of immunoblotting of sarcolemma and intracellular membranes and immunofluorescence localization with confocal microscopy. In vivo glucose extraction increased fivefold (P < .001) and was associated with net lactate release in the ischemic region. Ischemia led to an increase in the sarcolemma content of both GLUT-4 (15 +/- 2% to 30 +/- 3%, P < .02) and GLUT-1 (41 +/- 4% to 58 +/- 3%, P < .03) compared with the nonischemic region and to a parallel decrease in their intracellular contents. Immunofluorescence demonstrated the presence of both GLUT-4 and GLUT-1 on cardiac myocytes. GLUT-1 had a more prominent cell surface pattern than GLUT-4, which was primarily intracellular in the nonischemic region. However, significant GLUT-4 surface labeling was found in the ischemic region. CONCLUSIONS: Translocation of the insulin-responsive GLUT-4 transporter from an intracellular storage pool to the sarcolemma occurs in vivo during acute low-flow ischemia. GLUT-1 is also present in an intracellular storage pool from which it undergoes translocation to the sarcolemma in response to ischemia. These results indicate that both GLUT-1 and GLUT-4 are important in ischemia-mediated myocardial glucose uptake in vivo.

Animals↗

Seroprevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and rapid plasma reagin in a trauma population.

We evaluated the presence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and rapid plasma reagin (RPR) among patients admitted to our trauma unit from April 15 to June 30, 1993. Of 984 patients tested, we found 255 (26%) had evidence of exposure to one or more of these agents: HIV, 4%; HBV, 20%; HCV, 14%; and RPR, 1%. Thirty-eight percent of patients had more than one positive serology, 75% of the HIV patients, 49% of the HBV patients, and 66% of the HCV patients. There was no difference between penetrating and nonpenetrating trauma with respect to any of the viruses. The risk factors for HIV-positive patients were non-White race, positive drug screen, positive alcohol screen, and city resident. Risk factors for HBV patients were non-White race, positive drug screen, and city resident. Risk factors for HBC patients were male sex, non-White race, positive alcohol screen, positive drug screen, and city resident. The risk of blood-borne infections in this group of patients is substantial.

Cross-Sectional Studies↗

Aldosterone-mediated Na/K-ATPase expression is alpha 1 isoform specific in the renal cortical collecting duct.

In the renal cortical collecting duct (CCD), mineralocorticoid hormones, like aldosterone, augment the abundance of Na/K-ATPase molecules. It has been postulated that this response involves an isoform switch of the Na/K-ATPase catalytic subunit, alpha, as the molecular basis for the differential regulation of mineralo-corticoid-induced and constitutively expressed Na/K-ATPase pools. In opposition to this attractive hypothesis, three lines of independent evidence are presented which demonstrate that the CCD exclusively expresses the alpha 1 form despite mineralocorticoid-mediated changes in functional Na/K pump density. First, aldosterone increased [3H]ouabain binding in CCD 2.5-fold without changing the ouabain dissociation constant. Second, an electrophysiological assay for pump activity revealed that aldosterone increased maximum Na/K pump current in parallel with the change in ouabain binding without altering the apparent sodium affinity. Third, Western blot analysis with alpha isoform-specific, antipeptide antibodies demonstrated that aldosterone exclusively increased the total chemical pool of the alpha 1 form of the pump without inducing other alpha subunit isoforms. In summary, aldosterone increases the abundance of Na/K-ATPase molecules in the CCD which are pharmacologically, physiologically, and chemically indistinguishable from those that are normally expressed.

Aldosterone↗

Dose and temporal parameters in delaying injured optic nerve degeneration by low-energy laser irradiation.

Low-energy laser irradiation has been reported to postpone the degenerative processes in crushed optic nerves of rats, which are part of the nonregenerable mammalian central nervous system. In the present study, we evaluated the optimal irradiation parameters for this purpose. Optic nerves of 141 rats were subjected to crush injury and then irradiated through the eye, starting at different points of time before or after the injury, for different durations and periods, using various intensities of either helium-neon laser or noncoherent infrared light (904 nm). The effect was evaluated by measurements of the compound action potentials of the nerve segments between the site of injury and the optic chiasm. The compound action potential amplitude of the crushed nonirradiated nerves, as measured 2 weeks after the injury, was found to be 0.51 +/- 0.30 mV, in contrast to 3.10 +/- 1.03 mV measured in 232 normal nerves. Irradiation with a 10.5 mW helium-neon laser for 2 and 3 min once a day for 14 consecutive days resulted in maximal preservation of action potentials (1.78 +/- 0.72 and 1.95 +/- 0.71 mV, respectively). Irradiations beginning immediately prior to the injury were as effective as irradiations beginning soon after it. Irradiations for longer than 3 min or twice a day aggravated the damage. Noncoherent infrared light was ineffective or adversely affected the injured nerves. Our experiments suggest that optimal delay of posttraumatic optic nerve degeneration in rats is attainable with 10.5 mW helium-neon laser irradiations for 2 or 3 min once a day for 14 consecutive days.

Action Potentials↗

Necrotizing enterocolitis. New thoughts about pathogenesis and potential treatments.

Necrotizing enterocolitis (NEC) remains a major cause of morbidity and mortality in premature infants. An incomplete understanding of its pathogenesis has hampered efforts to devise an effective preventative strategy. New insights into the pathogenesis of NEC, particularly at the cellular and biochemical level, however, offer a rational basis for the development of new approaches to this disease.

Adrenal Cortex Hormones↗

Increase in plasma platelet-activating factor levels in enterally fed preterm infants.

Because platelet-activating factor (PAF) has been implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC), we designed a prospective study to examine plasma PAF levels during the first 14 days of feeding in a population of neonates of less than 32 weeks gestation. We found that significantly more patients had detectable plasma PAF levels on days 3 and 14 of feeding when compared to their prefeeding levels (7% on day 0 vs. 26% at day 3, p = 0.04; none on day 0 vs. 18.5% at day 14, p = 0.01). This finding could not be explained by decreased plasma activity of acetylhydrolase, the PAF breakdown enzyme, spontaneous endotoxinemia or a maturational effect. None of the infants who developed detectable PAF levels after feedings were begun went on to develop NEC. We conclude that our findings may reflect increased intestinal PAF production with the provision of feedings to some premature infants. However, this phenomenon by itself does not appear to be a sufficient condition for the subsequent development of NEC.

Acetyltransferases↗

Endogenous nitric oxide protects against platelet-activating factor-induced bowel injury in the rat.

Platelet-activating factor (PAF) causes bowel necrosis in animal models that is histologically identical to that seen in neonatal necrotizing enterocolitis, but little is known about endogenous mechanisms that might protect against PAF-induced bowel injury. We hypothesized that endogenous nitric oxide might represent such a protective mechanism. Adult male Sprague-Dawley rats were pretreated with 2.5 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), a potent nitric oxide synthase inhibitor, and given injections of 1.5 micrograms/kg PAF 15 min later. Animals treated with normal saline placebo, L-NAME alone, and PAF alone were also studied. Superior mesenteric artery blood flow and blood pressure were continuously recorded. At the end of 2 h or upon death of the animal, hematocrit was measured and intestinal samples were taken for histologic examination and determination of myeloperoxidase activity, a measure of intestinal neutrophil content. Compared with animals given PAF alone, animals pretreated with L-NAME followed by PAF developed significantly worse bowel injury (median injury scores: 2.5 versus 0.5, p = 0.005), hemoconcentration (final hematocrit 65.2 +/- 2.0% versus 53.9 +/- 1.0%, p < 0.001), and intestinal myeloperoxidase activity (12.45 +/- 1.94 U/g versus 6.51 +/- 0.57 U/g, p < 0.01). The last two effects were further accentuated when 10 mg/kg L-NAME was given before PAF. Treatment with sodium nitroprusside, a nitric oxide donor, for 10 min before and after PAF administration reversed the effects of L-NAME. Animals pretreated with phenylephrine rather than L-NAME did not develop worse injury than animals treated with PAF alone despite comparable reductions in superior mesenteric blood flow before PAF treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fulminant multiple system atrophy in a young adult presenting as motor neuron disease.

A 34-year-old man demonstrated rapidly progressive motor neuron disease and, late in his 9-month clinical course, exhibited ophthalmoplegia and dysautonomic symptoms. Neuropathology showed spinal and bulbar motor neuron disease with severe involvement of extraocular motor nuclei, degeneration of spinal sympathetic and bulbar parasympathetic nuclei, striatonigral degeneration, and early olivopontocerebellar atrophy. This case underscores the diversity of multiple system atrophy and demonstrates an unusually rapid course in a young patient.

Adult↗

Social competence promotion with inner-city and suburban young adolescents: effects on social adjustment and alcohol use.

This study assessed the impact of school-based social competence training on skills, social adjustment, and self-reported substance use of 282 sixth and seventh graders. Training emphasized broad-based competence promotion in conjunction with domain-specific application to substance abuse prevention. The 20-session program comprised six units: stress management, self-esteem, problem solving, substances and health information, assertiveness, and social networks. Findings indicated positive training effects on Ss' skills in handling interpersonal problems and coping with anxiety. Teacher ratings revealed improvements in Ss' constructive conflict resolution with peers, impulse control, and popularity. Self-report ratings indicated gains in problem-solving efficacy. Results suggest some preventive impact on self-reported substance use intentions and excessive alcohol use. In general, the program was found to be beneficial for both inner-city and suburban students.

Adolescent↗

Experimental necrotizing enterocolitis: the role of polymorphonuclear neutrophils.

Polymorphonuclear neutrophils (PMNs) play an important role in inflammation. Activated PMNs adhere to the vascular wall and release reactive oxygen radicals and enzymes, producing vascular injury. In the present study, we investigated whether PMNs play an important role in the pathogenesis of experimental necrotizing enterocolitis (NEC). NEC was induced in rats using platelet activating factor (PAF, 1 microgram/kg) and bacterial endotoxin (LPS, 1 mg/kg) intravenously. Neutropenia was accomplished by parenteral injection of Vinblastine (VB, 0.75 mg/kg) 4 days before the experiment to deplete the total white blood cell (WBC) and neutrophil counts. The animals were divided into 4 groups: (1) 1 microgram/kg PAF; (2) 1 mg/kg LPS; (3) 1 microgram/kg PAF + 1 mg/kg LPS; and (4) PMN depleted, 1 microgram/kg PAF + 1 mg/kg LPS. Combined administration of PAF and LPS produced prolonged hypotension (blood pressure 53.5 +/- 13.8 mm Hg at 2 hours), leukopenia (4,062 +/- 497.4), hemoconcentration (hematocrit 44.5% +/- 1.1%), reduced intestinal perfusion (74% +/- 13.3%), and segmental bowel necrosis. However, in VB-treated animals combined PAF + LPS induced only mild hypotension (84.3 +/- 9.2 mm Hg at 2 hours) and no hemoconcentration. In these animals the intestinal perfusion was normal, no bowel necrosis was observed, and the intestinal myeloperoxidase activity (.0034 +/- .0017 U/g tissue) was significantly lower than that of the nondepleted group (.0075 +/- .0012 U/g tissue). We conclude that the presence of neutrophils and/or neutrophil products play a major role in the pathogenesis of NEC.

Animals↗

Promoting competent young people in competence-enhancing environments: a systems-based perspective on primary prevention.

Recent studies indicate that 15-22% of American children and adolescents suffer from diagnosable mental disorders. Researchers estimate that 25-50% engage in risk behaviors for negative health and behavior outcomes, such as drug abuse, unwanted pregnancy, AIDS, delinquency, and school dropout. The prevalence of problem behaviors, as well as current social trends, demands that effective primary prevention programs be developed and disseminated. This article reviews successful family-, school-, and community-based prevention efforts aimed at reducing the incidence and severity of children's psychosocial problems. High-quality, comprehensive, competence-promotion programs that focus on both children and their socializing environments represent the state of the art in prevention. Establishing enduring, effective preventive interventions requires increased attention to program design, implementation, and institutionalization.

Achievement↗