A 32-year-old pregnant woman with malaise, headache, nausea, right upper quadrant abdominal pain, and facial swelling.
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Biomedical subjects
Publications and source records attributed to S Levine.
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Skeletal muscle plays an important role in respiratory and cardiovascular physiology. The ability to measure metabolic changes in skeletal muscle has been enhanced with the advent of magnetic resonance spectroscopy (MRS). MRS measurements have been used to understand the metabolic control of respiration and to evaluate metabolic changes in the muscle in patients with respiratory and cardiac diseases. The key to the respiratory control measurements is the ability to measure intracellular pH with MRS. Muscle oxidative metabolism has been measured in two ways: during steady-state exercise and using recovery kinetics. The similarities in the metabolic findings for pulmonary and coronary disease suggest the potential for some interesting common pathways.
During the course of a mild chemical peritonitis, new skeletal muscle fibers develop and persist over a twelve-month interval in the diaphragmatic peritoneum. Light and electron microscopic studies revealed that the ectopic fibers developed from myoblasts and myotubes to fully differentiated muscle cells in the same manner as normally situated skeletal muscle. The ectopic fibers were separated from the intrinsic muscle by dense connective tissue and an elastic lamina. Diaphragms taken from normal rats and transplanted to the omentum of isogeneic recipients also developed skeletal muscle neogenesis in the same ectopic location as in the normal diaphragm. Satellite cells, reactive fibroblasts in the peritoneum, mesenchymal stem cells or blood-borne myoblast precursor cells could be the source of these ectopic muscle fibers. The results of the present studies, however, cannot provide conclusive evidence for the origin of the new muscle fibers. Regardless of their source, the methods employed may represent a unique model for the development and prolonged maintenance of skeletal muscle fibers in a heterotopic location in vivo.
OBJECTIVE: The purpose of this study was to examine the independent effects of a variety of drinking indicators on self-reported work performance. METHOD: Data from a cross-sectional mailed survey (response rate = 71%) of managers, supervisors and workers (N = 6,540) at 16 worksites were analyzed. Average daily volume was computed from frequency and usual quantity reports. Drinking on the job included drinking during any of six workday situations. The CAGE was used to indicate alcohol dependence. Employees were also asked how frequently they drank to get high or drunk. Work performance was measured through a series of questions about work problems during the prior year. The number of times respondents experienced work performance problems was regressed on the four drinking measures, and a variety of demographic characteristics, job characteristics and life circumstances that might also negatively affect work performance. RESULTS: The frequency of self-reported work performance problems increased, generally, with all four drinking measures. In a multivariate model that controlled for a number of demographics, job characteristics and life-situations, average daily volume was no longer significantly associated with work performance but the other three drinking measures were. Interestingly, although moderate-heavy and heavy drinkers reported more work performance problems than very light, light, or moderate drinkers, the lower-level-drinking employees, since they were more plentiful, accounted for a larger proportion of work performance problems than did the heavier drinking groups. CONCLUSIONS: Employers should develop clear policies limiting drinking on the job and, in addition to employee assistance programs for problem drinkers, should develop worksite educational interventions aimed at informing all employees about the relationship between drinking behaviors and work performance.
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HYPOTHESIS: Induction of suprathreshold levels of stress-related hormone by systemic administration of epinephrine can change inner ear fluid homeostasis and function. BACKGROUND: Meniere's disease is frequently associated with high levels of anxiety and other forms of psychological disturbance. Most clinicians agree that emotional stress or severe anxiety can precipitate relapse or aggravate the symptoms. In general, it is known that stress-related hormones such as epinephrine, norepinephrine, vasopressin, aldosterone, and cortisol are released into systemic circulation in response to stress. Significantly higher levels of plasma norepinephrine and vasopressin in patients with Meniere's disease have been reported. METHODS: Concentrations of sodium and potassium in perilymph were measured by a flame photometer after systemic infusion of epinephrine (6.3 microg/min for 3 hours). Control animals were treated with equal volumes of 0.9% physiologic saline. Compound action potentials (CAP) elicited by brief tone bursts were measured before and 3 hours after the infusion of epinephrine. For chronic studies, epinephrine (10 microg/d/kg) was given by osmotic pump implanted subcutaneously for 1, 2, 3, and 4 weeks, respectively. Click- and tone-evoked auditory brain responses (ABRs) were measured at 1, 2, 3, and 4 weeks after epinephrine administration. RESULTS: Concentrations of sodium and potassium increased significantly in perilymph (p < 0.001 and p < 0.01) after epinephrine infusion over controls. The osmolality increased significantly in serum and perilymph after epinephrine infusion. The CAP threshold was significantly elevated at all frequencies. The shift of the CAP threshold caused by epinephrine tended to be larger at higher frequencies. In chronic studies, epinephrine administration caused a transient 20 to 45 dB threshold shift that increased with time and was relatively constant across frequency. CONCLUSIONS: There is good evidence to suggest that stress-related hormones such as epinephrine can alter inner ear fluid homeostasis and auditory function. This study confirmed this hypothesis and illuminated the processes of alteration by demonstrating specific changes in perilymph composition and auditory function.
Twenty-four hours of maternal deprivation results in persistent changes in the ACTH response to mild stress. These effects are dependent on the age of the neonate at the time of deprivation. Pups that were separated from the dam at postnatal days (pnd) 3-4 showed an enhanced stress-induced ACTH response at age 20, while pups deprived at pnd 11-12 displayed an attenuated ACTH response to stress at that time. The present study was designed to test the hypothesis that the immediate effects of deprivation at pnd 3 vs. pnd 11 would provide an explanation for these paradoxical effects observed at day 20. For this purpose, we measured the basal and the stress-induced ACTH and corticosterone (CORT) response at days 4 and 12, following 24 h of maternal deprivation. Furthermore, we examined whether similar differences in c-fos and CRH mRNA expression in the paraventricular nucleus (PVN) accompanied the differences in response characteristics of ACTH at pnd 20. The results indicate that changes in the ACTH and CORT responses were minimal after 24 h of maternal deprivation at day 4, whereas these hormones were markedly elevated following deprivation at day 12. The persistent effects also showed age-dependency: pups deprived early showed at pnd 20 an exaggerated ACTH response. Late deprived juveniles exhibited an attenuated ACTH response to stress at pnd 20 while in both conditions the CORT response was not different from the non-deprived litter mates. These persistent endocrine changes were accompanied by the changes in the neural stress markers. The expressions of c-fos and CRH mRNA in the PVN were at pnd 20 significantly greater in their controls in early-deprived animals. The late deprived juveniles showed a reduced response in these neural markers. In conclusion, the persistent alterations in ACTH are reflected by changes in c-fos and CRH mRNA, but these changes in endocrine and in neural stress markers do not appear to be related to any of the hormonal changes that occur at the time of maternal deprivation.
After 24 hr of maternal deprivation, significant elevations in ACTH and the naturally occurring glucocorticoid corticosterone (CORT) are observed during the stress-hyporesponsive period. The deprived pups also showed in the paraventricular nucleus (PVN) a marked increase of stress-induced c-fos mRNA and a reduction of corticotropin-releasing hormone (CRH) and glucocorticoid receptor (GR) mRNA; in hippocampal CA1, a reduction of the mineralocorticoid receptor (MR) and GR was observed. Here, we examined whether these changes are reversed by (1) preventing the elevations of CORT characteristic for the 11-d-old deprived pups by administering the synthetic glucocorticoid dexamethasone (DEX); or (2) reinstating some aspects of maternal behavior. The pups were either (1) left undisturbed, (2) stroked, or (3) stroked and episodically fed by cheek cannulation. At postnatal day 12, peripheral and neural stress markers were measured. Nondeprived animals served as controls. Experiment 1 demonstrates that although CORT was kept low by DEX, the central effects on CORT receptors, CRH, and c-fos mRNA were still present, except for MR in hippocampal CA1. Experiment 2 shows that stroking alone prevented the stress-induced rise in ACTH and c-fos mRNA and in the reduction in CRH and MR mRNA. In pups that were fed and stroked, CORT and GR mRNA resembled nondeprived controls. In conclusion, the changes in peripheral endocrine responses and in the brain cannot be attributed to the effect of elevated CORT concentrations, which are characteristic of the maternally deprived neonate. However, reinstating some components of the dams' nurturing behavior can reverse the effects evoked by maternal deprivation.
It is well established that lithium can cause morphologically visible damage to the kidneys of humans and animals. Although the clinical significance of its nephrotoxicity is debatable, it would be desirable to find a method to prevent lithium's effect on the kidneys. Toward this end, we have developed a novel method for producing nephrotoxicity that will be useful for research on prevention. A single, large, toxic dose of lithium chloride (LiCl) caused necrosis of the distal convoluted tubules, which was visible by light microscopy in 30 min, had fully developed in 1 h, and had disappeared by the next day. The lesions were seen after i.p. or i.v. injections of fasted rats of three different strains. Equivalent doses of NaCl, KCl, MgCl2 and combinations thereof had no such effect, nor did they inhibit nephrotoxicity when incorporated into the LiCl solution. However, relatively small doses of LiCl injected by any route 3 or 24 h beforehand prevented the nephrotoxicity. The mechanism of prevention is not known, but it does not involve reduction of lithium levels in the kidneys.
Aquaporin 2 (AQP2) transfected into LLC-PK1 cells functions as a vasopressin-regulated water channel that recycles between intracellular vesicles and the plasma membrane upon vasopressin stimulation. The green fluorescent protein (GFP) of the jellyfish, Aequorea victoria, was used as an autofluorescent tag to monitor AQP2 trafficking in transfected LLC-PK1 cells. Two chimeras were constructed, one in which GFP was fused to the amino-terminus of AQP2 [GFP-AQP2(NT)] and the second in which it was fused to the carboxyl-terminus [AQP2-GFP(CT)]. The GFP-AQP2(NT) chimera trafficked in a regulated pathway from intracellular vesicles to the basolateral plasma membrane in response to vasopressin or forskolin stimulation of cells. In contrast, the AQP2-GFP(CT) chimera expressed in LLC-PK1 cells was localized constitutively on both apical and basolateral plasma membranes. The cellular location of this chimera was not modified by vasopressin or forskolin. Thus, while the GFP-AQP2(NT) chimera will be useful to study AQP2 trafficking in vitro, the abnormal, constitutive membrane localization of the AQP2-GFP(CT) chimera suggests that one or more trafficking signals exist on the carboxyl-terminus of the AQP2 protein.
Although evidence suggests that social networks reduce the risk of mortality and are negatively associated with severe mental disability, little is known about their relationship to everyday functioning and health-related quality of life (HRQoL). In addition, the importance of social networks in the presence of chronic stress remains unclear. We examined the association between social networks and aspects of mental functioning (mental health, vitality and role-emotional functioning) and the relationship between social networks and mental functioning in the presence of stressors. Multiple linear and logistic regression models were used to examine data in 47,912 middle-aged and older healthy women. The Medical Outcomes Study Shortform Health Survey measured dimensions of quality of life. We observed strong associations between levels of social networks and multivariate-adjusted quality of life scores, particularly in potentially high stress situations. Compared to the most socially integrated, women who were socially isolated had reductions in mental health and vitality scores of 6.5 and 7.4 points, respectively and a 60% increased risk of limitation in role-emotional functioning. Social networks are positively associated with mental functioning in women. This association is strongest for women reporting high levels of home and work stressors.
Diaphragmatic fatigue has been associated with increased production of reactive oxygen species. Among the defenses against reactive oxygen species is the glutathione redox system. The selenium-dependent enzyme glutathione peroxidase is an important component of this system. Thus, we hypothesized that selenium deficiency would lower glutathione peroxidase activity and render the diaphragm more susceptible to a mild exertional protocol. Sprague-Dawley rats were fed a selenium-deficient or control diet for 12 weeks then divided into four experimental groups: (1) unloaded, basic diet with selenium supplementation (control); (2) unloaded, selenium-deficient diet; (3) loaded, basic diet with selenium supplementation; and (4) loaded, selenium-deficient diet. Diaphragmatic in vitro contractile properties, glutathione peroxidase activity and glutathione content were measured. During inspiratory resistive loading, the animals breathed against an inspiratory resistor at 70% of maximal airway pressure until the target pressure was not achieved for five consecutive breaths. Selenium deficiency resulted in a significant decrease in diaphragmatic glutathione peroxidase activity, without changes in total glutathione content. Neither selenium deficiency nor inspiratory resistive loading alone impaired diaphragmatic contractility. Selenium deficiency in conjunction with inspiratory resistive loading resulted in a significant decrease in diaphragmatic twitch and tetanic force, with a downward shift in the force/frequency curve. These data suggest that selenium deficiency lowers diaphragmatic glutathione peroxidase activity, and when these animals are subjected to the oxidative stress of resistive loading, there is an impairment in muscle function. We conclude that a functional glutathione peroxidase is necessary to protect the diaphragm against the effects of resistive loading.
OBJECTIVE: The diagnosis of Meniere's disease has always been a source of confusion. There is no single test that is definitive for the diagnosis. Recent advances have enabled clinicians to noninvasively test the function of the inner ear and its associated neural pathways. The electrocochleogram (ECOG) has been advocated as a reliable test that is diagnostic for Meniere's disease. This study was undertaken to assess the value of ECOG in establishing the diagnosis of Meniere's disease. STUDY DESIGN: Patients who were suspected of having Meniere's disease were prospectively entered into a study of the diagnostic value of ECOG. Each patient had a complete evaluation including a detailed history, physical examination, laboratory studies, and audiometric tests. SETTING: University otolaryngology clinic. PATIENTS: A group of 199 patients who presented to a neurotology clinic and were suspected to have symptoms consistent with Meniere's disease. INTERVENTION: ECOG testing. MAIN OUTCOME MEASURES: Audiometric thresholds, action potential magnitude (AP), summating potential amplitude (SP), AP latency, and clinical evaluations were assessed. RESULTS: The ECOG was found to correlate with historical and audiometric criteria that are used to diagnose the disease. The percentage of abnormal ECOG did not correlate with stage of disease or duration of time that symptoms were present. CONCLUSIONS: The ECOG has limited value in the diagnosis of Meniere's disease. It appears to correlate with the length of time patients experience symptoms and their audiometric findings. It was not correlated with the number of symptoms that the patient experienced at the time that the study was conducted.
Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.
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Hemorrhage and congestion were not uniformly distributed along the small intestine during systemic anaphylaxis in rats. Duodenum had little hemorrhage and congestion and the terminal ileum had even less. Maximum involvement occurred in jejunum of 13% of rats, in ileum of 47%, and in both jejunum and ileum of 40%. Sequential scoring along the entire length of small intestine revealed different patterns of distribution with more than one peak of intensity in some of the rats. Within a lesioned area, banding was common except where hemorrhage and congestion were so severe as to obliterate all patterns. Banding represented a gradient of injury with respect to the vascular supply. The pale stripes (less severe hemorrhage) contained the penetrating vessels derived from the terminal mesenteric arcades. The dark stripes (more severe hemorrhage) did not contain such vessels. In addition, the mesenteric side of the intestine was less affected than the antimesenteric side. This constituted a second gradient that might also be related to the distance from the vascular supply. In both instances, proximity to larger blood vessels had a protective effect. These two gradients and the variable sites and patterns of distribution have not been described previously in intestinal anaphylaxis. Gradients and the variability of the distribution of lesions in intestinal anaphylaxis should be considered in experiments on pathogenesis and altered function.