Biomedical subjects
Publications and source records attributed to J R Wilson.
A modified oxygen delivery system was developed for a patient too claustrophobic for the monoplace chamber or the hood in the multiplace chamber. The adaptation delivered O2 through the patient's tracheostomy by means of a soft cervical collar, a pediatric tracheostomy cuff, and a T-tube.
FK506 is an important immunosuppressant that has shown great promise in the treatment of autoimmune diseases. Approximately 5% of patients receiving FK506 develop major central nervous system toxicity, but the peripheral nerves are usually spared. During 1990-1991, some 1000 patients received liver transplants under FK506 immunosuppression. Of these, 3 patients developed severe multifocal demyelinating sensorimotor polyneuropathy 2-10 weeks after initiation of FK506 therapy. Improvement followed plasmapheresis or intravenous immunoglobulin (IVIG), suggesting an immune-mediated cause. Although autoimmune neuropathy has been previously reported in immune-deficient states such as Hodgkin's disease and AIDS, it is not an expected complication of immunosuppressive therapy. However, others have shown that this phenomenon can be produced in rats with cyclosporine A (CsA), whose effects on T-cell subsets are similar to those seen with FK506. These T-cell subset changes may have precipitated this dysimmune neuropathy in our patients.
Hypoglossal nerve damage is a known complication of carotid endarterectomy, occurring in approximately 5% of endarterectomies. The vast majority of these patients recover without functional disability from this injury even if the tongue remains hemiplegic. We report 2 patients who suffered hypoglossal nerve section during neck surgery. Although they were initially mildly symptomatic, they developed increasingly severe dysarthria and dysphagia beginning 4 months after surgery. EMG revealed abnormal coactivation of the genioglossus and styloglossus muscles on the affected side, suggesting aberrant reinnervation. Aberrant reinnervation is a well-known complication of facial nerve injury, but has not been previously recognized in hypoglossal nerve injury. Like the face, the tongue is composed of many muscles that must perform complex movements. Normally, injury to one hypoglossal nerve causes little or no disability, but when aberrant reinnervation occurs, the tongue no longer moves in a coordinated manner, and significant dysarthria ensues.
It has been postulated that skeletal muscle release of potassium contributes to exercise-induced vasodilation of skeletal muscle arterioles. To determine whether potassium produces muscle arteriolar vasodilation in humans, we measured plethysmographic forearm blood flow and brachial venous potassium concentrations during brachial arterial infusion of potassium (0.6, 3, 6, 15, and 30 mueq.min-1.100 ml forearm volume-1) in nine normal subjects. Infusion of potassium decreased forearm vascular resistance, with an increase in brachial venous potassium of 1 meq/l decreasing forearm vascular tone by 25-30%. We then measured plasma potassium concentrations during forearm and upright bicycle exercise in 15 normal subjects. Forearm exercise at 0.6 W decreased forearm vascular resistance by 83%, whereas brachial venous potassium increased by only 0.5 +/- 0.2 meq/l (both P < 0.05). Maximal bicycle exercise increased systemic potassium concentrations by 1.2 +/- 0.2 meq/l. These findings indicate that potassium produces muscle arteriolar vasodilation in humans and therefore supports the hypothesis that potassium release from exercising muscle contributes to exercise-induced vasodilation. The relatively small change in venous potassium noted during forearm exercise despite marked forearm vasodilation suggests that local potassium release is only a small contributor to exercise-induced vasodilation. However, potassium release during maximal exercise may have significant vasodilatory effects on arterioles both in exercising and nonexercising tissues.
Near-infrared (NIR) spectroscopy is a noninvasive technique that uses the differential absorption properties of hemoglobin to evaluate skeletal muscle oxygenation. Oxygenated and deoxygenated hemoglobin absorb light equally at 800 nm, whereas at 760 nm absorption is primarily from deoxygenated hemoglobin. Therefore, monitoring these two wavelengths provides an index of deoxygenation. To investigate whether venous oxygen saturation and absorption between 760 and 800 nm (760-800 nm absorption) are correlated, both were measured during forearm exercise. Significant correlations were observed in all subjects (r = 0.92 +/- 0.07; P < 0.05). The contribution of skin flow to the changes in 760-800 nm absorption was investigated by simultaneous measurement of skin flow by laser flow Doppler and NIR recordings during hot water immersion. Changes in skin flow but not 760-800 nm absorption were noted. Intra-arterial infusions of nitroprusside and norepinephrine were performed to study the effect of alteration of muscle perfusion on 760-800 nm absorption. Limb flow was measured with venous plethysmography. Percent oxygenation increased with nitroprusside and decreased with norepinephrine. Finally, the contribution of myoglobin to the 760-800 nm absorption was assessed by using 1H-magnetic resonance spectroscopy. At peak exercise, percent NIR deoxygenation during exercise was 80 +/- 7%, but only one subject exhibited a small deoxygenated myoglobin signal. In conclusion, 760-800 nm absorption is 1) closely correlated with venous oxygen saturation, 2) minimally affected by skin blood flow, 3) altered by changes in limb perfusion, and 4) primarily derived from deoxygenated hemoglobin and not myoglobin.
BACKGROUND: Skeletal muscle metabolic abnormalities have been described in patients with heart failure that are independent of total limb perfusion, histochemical changes, and muscle mass. However, these skeletal muscle metabolic abnormalities may result from tissue hypoxia caused by maldistribution of flow. Myoglobin is an O2 binding protein that can indirectly assess tissue hypoxia. METHODS AND RESULTS: In vivo measurement of deoxymyoglobin was performed by use of proton (1H) magnetic resonance spectroscopy in 16 heart failure (HF) (left ventricular ejection fraction = 20 +/- 6%; VO2 = 14.5 +/- 5.1 mL/kg per minute) and 7 healthy (Nl) subjects. Simultaneous phosphorus (31P) magnetic resonance spectroscopy and near-infrared spectroscopy also were obtained to examine muscle metabolism and oxygenation. Supine calf plantarflexion was performed every 4 seconds. Incremental steady-state work was performed. A second exercise protocol studied rapid incremental (RAMP) exercise with plantarflexion every 2 seconds. Arterial occlusion at end exercise provided physiological calibration for myoglobin and hemoglobin signals. With steady-state exercise, the work slope, ie, inorganic phosphorus to phosphocreatine ratios versus work, was significantly greater in patients with heart failure (Nl: 0.18 +/- 0.08; HF: 0.40 +/- 0.32 W-1; P < .05). Intracellular pH was reduced significantly at end exercise in patients but not healthy subjects. Despite these metabolic abnormalities, muscle oxygenation derived from 760- to 850-nm absorption was comparable in both groups throughout exercise. The relation of inorganic phosphorus/phosphocreatine (P1/PCr) ratio and muscle oxygenation was shifted upward in patients with heart failure such that at the same muscle oxygenation, Pi/PCr ratio in these patients was increased. No deoxymyoglobin signals were observed at rest. At maximal exercise, 4 of the healthy subjects and 3 of the patients exhibited deoxymyoglobin (P = NS). With RAMP exercise, the work slope was again significantly greater in patients with heart failure (Nl: 0.21 +/- 0.10; HF: 0.57 +/- 0.32 W-1; P < .05). Intracellular pH again was significantly decreased at end exercise in patients but not healthy subjects. Five of the healthy subjects and 3 of the heart failure patients had deoxymyoglobin signal (P = NS). With arterial occlusion, deoxymyoglobin was seen in all subjects. CONCLUSION: Abnormal skeletal muscle metabolism in patients with heart failure usually occurs in the absence of myoglobin deoxygenation, suggesting that the abnormalities are not a result of cellular hypoxia during exercise with minimal cardiovascular stress.
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OBJECTIVE: To describe the trends in firearm fatalities in California between 1987 and 1991 and the 153 firearm injuries in girls and women treated at the King/Drew Medical Center, Los Angeles, Calif, from September 1, 1991, to December 31, 1992. DESIGN: Retrospective study. SETTING: The study was conducted at the King/Drew Medical Center, a university-based county hospital, one of the major trauma centers in Los Angeles. PATIENTS: At the King/Drew Medical Center, 32 patients (21%) required at least one major procedure. Of the 16 patients who died, 14 (88%) died in the emergency department of wounds to the head (six patients), chest (five patients), and abdomen (three patients). The odds ratio of dying if injured in the head, face, or neck was 2.23, and in the abdomen, 1.0. Surgeons rarely probe for the underlying cause of injury. MAIN OUTCOME: The outcome has been a 2.28-fold increase in deaths in girls and women aged 10 to 19 years. RESULTS: Much of the violence against girls and women is perpetrated by those known to them. CONCLUSION: Firearms are the most frequently used weapon in female homicides. Firearm fatalities in women represent a significant problem among all ethnic groups. Trauma centers must take the lead in the collection of meaningful data to implement effective gender- and ethnic-specific violence prevention strategies.
Users of hypertext systems require some form of navigation aid or 'browser'. Typically these have been produced as schematic representations of the hypertext network. The advent of 'virtual reality' technology, and particularly less costly forms of this, offers new possibilities for hypertext navigation whereby information can be presented in the form of a virtual environment. Users can then move around the virtual world in much the same conceptual fashion as they move around the real world. Based upon an extensive review of hypertext navigation problems and the aiding systems proposed to deal with these, four different types of navigation aid have been built; these are schematic and spatial representations in two and three dimensions. Of particular interest is the 3D spatial representation, built as a virtual environment in Virtus Walkthrough; the proposition is that such a virtual world navigation aid will offer substantial usability advantages for hypertext databases.
The transport and metabolism of L-alanine by Giardia intestinalis trophozoites was characterised. G. intestinalis formed 14CO2 from L-[1-14C]alanine (1 mM) at a rate of 4.8 nmol min-1 (mg protein)-1 at 30 degrees C. The system was saturable, with an apparent Km of 0.29 mM for alanine, and a maximal rate of 6.1 nmol min-1 (mg protein)-1. L-cycloserine inhibited the metabolism, as did a number of amino acids including glycine, serine and threonine. D-alanine and 2-aminoisobutyrate had no effect. G. intestinalis was shown to have a functional transport system for L-alanine. The transporter was saturable with a Km of 1.5 mM and a maximal velocity of 6.1 nmol min-1 (mg protein)-1 at 23 degrees C. It was temperature dependent, with a Q10 of 2.2 and activation energy of 15.9 kcal mol-1. It was not inhibited by potential inhibitors of energy dependent transport. Glycine, L-serine and L-threonine potently inhibited L-alanine transport, whereas D-alanine, beta-alanine and 2-aminoisobutyrate had no effect. L-serine competitively inhibited L-alanine influx. In trophozoites preloaded with [3H]alanine, rapid exchange occurred with external L-alanine and L-serine, but not with D-alanine confirming that L-alanine and L-serine share a common transport site. These observations indicate that G. intestinalis has a functional alanine transporter, which may be an antiport catalysing the exchange of alanine, serine, glycine and threonine.
Acute T-2 toxin treatments alter biogenic monoamine concentrations in the brain; however, these perturbations have not been well documented or demonstrated in feeding trials. In this study, the effect of dietary T-2 toxin on regional brain concentrations of biogenic monoamines and their metabolites was investigated in male rats fed a semi-synthetic diet containing 0, 2.5 or 10 ppm T-2 toxin for either 7 or 14 days. Reduction in feed consumption, feed efficiency and weight gain was observed in rats fed either 2.5 or 10 ppm T-2 toxin. This effect was transient in animals fed the 10 ppm T-2 toxin diet, with feed consumption, feed efficiency and weight gain improving significantly during wk 2. T-2 toxin affected brain biogenic monoamine concentrations. In the nucleus raphe magnus, serotonin, 5-hydroxy-3-indoleacetic acid and norepinephrine increased in a dose-dependent manner, and dopamine increased transiently. In the substantia nigra of rats fed 10 ppm T-2, epinephrine increased after 7 days and norepinephrine decreased after 14 days, when compared with controls. Dihydroxyphenylacetic acid concentrations in the paraventricular nucleus and medial forebrain bundle were lower in T-2 toxin-treated rats than in control animals. The observed effects of T-2 toxin on brain monoamines and the resulting neurochemical imbalance may account for the physiological manifestation of trichothecene intoxication.
Exertional intolerance is a major clinical problem in ambulatory patients with chronic heart failure and is associated with both muscle fatigue and dyspnea. The increased muscle fatigability is most likely caused by a combination of muscle underperfusion and muscle deconditioning; patients frequently exhibit skeletal muscle atrophy, altered muscle metabolism and reduced mitochondrial-based enzyme levels, consistent with deconditioning. The muscle underperfusion is largely due to impaired arteriolar vasodilation within exercising muscle. Exertional dyspnea appears to be due to increased respiratory muscle work mediated by excessive ventilation and decreased lung compliance. Both excessive carbon dioxide production, secondary to increased muscle lactate release, and increased lung dead space contribute to the excessive ventilation. Decreased lung compliance is caused by chronic pulmonary congestion and fibrosis. Optimal management of exercise intolerance in patients with heart failure requires an understanding of the role of these multiple potential contributors to exertional fatigue and dyspnea.
Data from 42 male and 58 female subjects who participated in the Colorado Alcohol Research on Twins and Adoptees (CARTA) project were subjected to model-fitting analyses. The aim of the present study was to use linear structural equation models to determine whether differences in previously measured psychomotor sensitivity to alcohol predict differences in self-reported alcohol consumption over a 4-year period. LISREL model-fitting results indicate that, for male subjects, only rail walking insensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. For females, only hand steadiness sensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. The results for males support a hypothesis that would consider alcohol insensitive individuals at greater risk for alcohol abuse. The female results, however, would argue against such a hypothesis. With only one measure of sensitivity predicting alcohol use at only one out of four time points, in both men and women, the overall results suggest that our three measures of psychomotor sensitivity to alcohol are, in general, poor predictors of alcohol consumption in this sample.
It has been postulated that endothelial release of prostaglandins contributes to exercise-induced vasodilation of skeletal muscle arterioles. To test this hypothesis, 12 normal subjects underwent brachial arterial and venous catheter insertion and instrumentation of their forearm to measure plethysmographic forearm blood flow. Forearm blood flow and arterial and venous 6-ketoprostaglandin F1 alpha (PGF1 alpha) and prostaglandin E2 (PGE2) were then measured during two levels of wrist flexion exercise (0.2 and 0.4 W). In nine of the subjects, exercise was repeated after intra-arterial infusion of indomethacin (0.3 mg/100 ml forearm vol). Exercise increased forearm blood flow (2.0 +/- 0.2 to 12.1 +/- 1.1 ml.min-1.100 ml-1) and forearm release of PGF1 alpha (162 +/- 28 to 766 +/- 193 pg.min-1.100 ml-1) and PGE2 (26 +/- 6 to 125 +/- 46 pg.min-1.100 ml-1) (all P < 0.05). Indomethacin virtually abolished forearm prostaglandin release and reduced forearm blood flow at rest (2.2 +/- 0.2 to 1.7 +/- 0.2 ml.min-1.100 ml-1), at 0.2 W (6.3 +/- 0.7 to 5.4 +/- 0.7 ml.min-1.100 ml-1), and at 0.4 W (12.2 +/- 1.5 to 10.3 +/- 1.3 ml.min-1.100 ml-1) (all P < 0.02). These data suggest that release of vasodilatory prostaglandins contributes to exercise-induced arteriolar vasodilation and hyperemia in skeletal muscle.
Release of endothelium-derived relaxing factor (EDRF) from the vascular endothelium may contribute to skeletal muscle arteriolar vasodilation during exercise. The present study was undertaken to test this hypothesis. Ten normal subjects underwent brachial arterial catheter insertion and instrumentation of their forearm to measure plethysmographic forearm blood flow. Forearm blood flow was then measured at rest, during two levels of wrist flexion exercise (0.2 and 0.4 W), and during 0.4-W exercise with concurrent infusion of norepinephrine (100 ng.min-1 x 100 ml forearm volume-1). Measurements were made with and without infusion of N-monomethyl-L-arginine (L-NMMA) (0.1-0.2 mg.min-1 x 100 ml forearm volume-1), a specific inhibitor of EDRF synthesis. Infusion of L-NMMA reduced resting forearm blood flow (control: 2.5 +/- 0.4 vs. L-NMMA: 1.5 +/- 0.1 ml.min-1 x 100 ml-1) and markedly reduced forearm blood flow response to acetylcholine (5 micrograms.min-1 x 100 ml forearm volume-1) (control: 20.2 +/- 2.9 vs L-NMMA: 4.0 +/- 1.0 ml.min-1 x 100 ml-1; both P < 0.01). However, L-NMMA had no significant effect on flow responses to exercise (0.2 W: 8.3 +/- 1.1 vs. 8.3 +/- 1.2; 0.4 W: 13.8 +/- 1.7 vs. 13.5 +/- 1.7; 0.4 W + norepinephrine: 10.3 +/- 2.4 vs. 9.4 +/- 2.6 ml.min-1 x 100 ml-1; all P = NS). These findings suggest that release of EDRF from the vascular endothelium contributes to skeletal muscle arteriolar vasodilation at rest but does not contribute to the arteriolar vasodilation produced by exercise.
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BACKGROUND: Exertional fatigue in patients with chronic heart failure is usually attributed to skeletal muscle underperfusion. Recently, skeletal muscle atrophy, abnormal muscle metabolic responses, and reduced muscle enzyme levels have been noted in such patients, raising the possibility that some patients may develop muscle fatigue due to intrinsic muscle abnormalities. The present study was undertaken to determine if a subpopulation of patients with heart failure develops exertional fatigue due to skeletal muscle dysfunction rather than to reduced muscle flow. METHODS AND RESULTS: All exercise hemodynamic studies performed in our laboratory on patients with heart failure were reviewed to identify those who exhibited peak exercise VO2 levels < or = 18 ml.min-1 x kg-1 due to leg fatigue and who underwent insertion of a Swan-Ganz catheter and leg blood flow catheter. Thirty-four patients were identified. Six normal subjects were also studied to define normal leg flow and femoral venous lactate responses to exercise. Patients with peak exercise leg flow levels within the normal mean flow level +/- 2 SEM were considered to have normal skeletal muscle flow during exercise. Nine of the 34 patients with heart failure were found to have normal leg blood flow during exercise. All of these patients terminated exercise due to leg fatigue, and all exhibited abnormal increases in femoral venous lactate concentrations (slope of work load versus femoral venous lactate: normal, 0.33 +/- 0.07 mg/W; heart failure with normal flow, 0.81 +/- 0.08 mg/W; p < 0.002). There was no significant difference between patients with normal leg flows and those with reduced flow in age, ejection fraction, and resting hemodynamic measurements. However, patients with normal flows exhibited more normal cardiac output responses to exercise and tended to have higher peak exercise VO2 (14.1 +/- 0.9 versus 11.5 +/- 0.7 ml.min-1 x kg-1, p < 0.05). CONCLUSIONS: A substantial percentage of patients with chronic heart failure develop exertional fatigue due to skeletal muscle dysfunction rather than to reduced skeletal muscle blood flow. In such patients, therapeutic interventions probably should be directed at improving the skeletal muscle abnormalities rather than at improving skeletal muscle flow.
Questionnaire data from the Colorado Alcohol Research on Twins and Adoptees (CARTA) were analyzed to explore the reliability of sibling responses to items from the CARTA Family Alcoholism History Questionnaire (FHQ) concerning parental drinking behaviors. Subjects included 142 pairs of male and female, twin and nontwin siblings who reported on paternal and maternal problem drinking. FHQ items were summed to produce drinking-problem scales for fathers and mothers. There was generally good concordance across sibling reports of parental problem-drinking symptoms. There was a significant gender difference in that male offspring were more in agreement about their mothers' drinking behavior, while female offspring were more in agreement about their fathers' drinking behavior. For the most part, objective items, such as having two or more drunk-driving arrests, were more reliable (paternal kappa total = .56, maternal = .66) than subjective items, such as being happy only when drinking (paternal = .24, maternal = -.03). This evidence for reliability of sibling reports about parental drinking does seem to validate the use of such questionnaire data in alcohol studies.