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Biomedical subjects

J Weinberg

Publications and source records attributed to J Weinberg.

At least 37 records · Page 2Linked to original sources

Respiratory response to exercise in postpolio patients with severe inspiratory muscle dysfunction.

OBJECTIVES: To evaluate the limiting factors of exercise performance and to analyze the respiratory strategies adopted during exercise in postpolio patients with severe inspiratory muscle dysfunction. PATIENTS: Five patients with prior poliomyelitis associated with scoliosis and with respiratory muscle dysfunction (mean vital capacity, 1.74L [range, 1.1 to 2.4]) were studied at rest and during leg or arm cycle exercise. METHODS: Gas exchange was examined by arterial blood gases and mass spectrometry of expired air. Ventilatory mechanics were studied by measurement of esophageal and gastric pressures. RESULTS: Blood gases at rest were normal, except for subnormal PO2 levels in three patients. In all but one patient, ventilatory insufficiency was the limiting factor for exercise. A compensatory breathing pattern with abdominal muscle recruitment during expiration was present already at rest in three of the patients. The pressures generated by the diaphragm were below fatiguing margins, ie, levels that in healthy subjects can be sustained for at least 45 minutes. CONCLUSIONS: The extent of ventilatory dysfunction was not evident in blood gas values at rest; however, it was revealed by blood gas values during the exercise test. Diaphragm fatigue seems to be avoided at the cost of impaired blood gases.

Adult↗

Differential effects of harassment on cardiovascular and salivary cortisol stress reactivity and recovery in women and men.

To explore the differential effects of harassment on cardiovascular and neuroendocrine stress reactivity and recovery, 28 men and 32 women were randomized to a harassment or no-harassment control condition (four groups in total). The harassment consisted of three scripted statements delivered during performance of a mental arithmetic stress task. The harassing statements were delivered on a fixed schedule during the task by a same-gender experimenter. Cardiovascular, salivary cortisol, and state affect measures were taken at baseline, immediately posttask, and throughout an extended recovery period. In comparison to the control condition, harassment accentuated the stress reactivity responses on all measures, physiological and self-report of subjective affect. In addition, several gender differences in response to the stressor and during the recovery period were observed. Harassed men had the largest reactivity on cortisol and diastolic blood pressure, whereas the harassed women showed a more pronounced response on heart rate and self-reported hostility. The harassed groups were the only ones to show significant cortisol responses. Within the harassed condition, comparison of effect sizes revealed that cortisol reactivity in men was twice that of women. Control groups did not exhibit significant cortisol changes. During the recovery period, harassed men exhibited attenuated return to baseline on cardiovascular indices and cortisol, whereas women, overall, tended to exhibit an overcompensation response on cardiovascular measures. These results contribute to showing a pathway that may link negative affect (i.e., hostile or angry feelings) with the development of cardiovascular disease.

Adolescent↗

Interactive effects of psychosocial stressors and gender on mouse mammary tumor growth.

We have previously demonstrated that social housing condition significantly affects the growth rate of the androgen-responsive Shionogi mouse mammary carcinoma (AR SC115) in male mice. The present study examined the effects of social housing condition and acute daily exposure to a novel environment on the growth rate of an androgen-independent variant of the AR SC115 carcinoma, designated SC115V, in male and female mice. Immediately following tumor cell injection, male and female mice that were reared as individuals (I) or in groups (G) of the same sex were rehoused either from individual to same-sex groups (IG) or from group to individual (GI), or remained in their group housing condition (GG). Approximately half the mice in each housing condition were subjected to acute daily exposure to novel environments (novelty stress), a treatment shown previously to increase the significant difference in tumor growth rates between male mice in the IG and GI housing conditions. The remaining mice were left undisturbed (no novelty stress). In the presence of acute daily novelty stress, the growth rate of the SC115V tumor was significantly increased in GI compared to IG males. However, no significant differences in SC115V tumor growth rates among nonstressed GI, IG, or GG males were observed. For females, in contrast to males, acute daily novelty stress significantly decreased tumor growth in GI compared to IG mice, whereas under nonstressed conditions, tumor growth rate was significantly increased in GI compared to IG females. Neither housing condition nor novelty stress altered estrous cyclicity, nor did the stage of the estrous cycle at the time of tumor cell injection influence tumor growth rates. These findings suggest that social housing condition and novelty stress may interact to produce differential effects on the growth rate of the SC115V tumor in male and female mice.

Animals↗

Chronic intermittent stress does not differentially alter brain corticosteroid receptor densities in rats prenatally exposed to ethanol.

Prenatal ethanol exposure produces hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. The present study tested the hypothesis that decreased corticosteroid receptor densities at HPA feedback sites may play a role in deficient feedback inhibition and the resultant HPA hyperresponsiveness that is observed following prenatal ethanol exposure. Brains of adult Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF) and ad libitum-fed control (C) treatment groups were examined for both mineralocorticoid receptor (MR; Type I) and glucocorticoid receptor (GR; Type II) densities using a cytosolic binding assay. Experiment 1 compared the effects of chronic intermittent stress (Stress Regimen I) and corticosterone (CORT) pellet implants on hippocampal corticosteroid receptor densities in control rats. Experiment 2 determined whether exposure to Stress Regimen I would differentially downregulate and whether adrenalectomy (ADX) would differentially upregulate hippocampal corticosteroid receptors in E compared with PF and C animals. Experiment 3 examined the effects of a modified chronic intermittent stress regimen (Stress Regimen II) on corticosteroid receptor densities at several HPA feedback sites (hippocampus, prefrontal cortex, hypothalamus, and anterior pituitary) in E compared with PF and C animals. CORT pellet implants significantly downregulated hippocampal GR and MR densities in control males and females. Exposure to Stress Regimen I produced downregulation of hippocampal GRs and MRs in males comparable with that produced with CORT pellet implants, and significant downregulation of hippocampal GRs in females across all prenatal treatment groups. This stress regimen also elevated basal plasma CORT levels without concurrent changes in plasma CBG levels, and increased relative adrenal weights in both males and females. In addition, upregulation of hippocampal GRs occurred at 7 days compared with 24 h following ADX in females that had previously been exposed to this stress regimen. Following exposure to Stress Regimen II, both the downregulation of hippocampal corticosteroid receptors and the increase in basal CORT levels in males and females appear to have been abolished by the changes in housing condition during the period of chronic stress. Importantly, prenatal ethanol exposure did not differentially alter GR or MR densities at any feedback site under non-stressed conditions. Exposure to Stress Regimen II, revealed subtle effects of prenatal treatments on hippocampal GRs however it is unlikely that these changes in corticosteroid receptor densities mediated the feedback inhibition deficits observed in E animals. Together, these data demonstrate that: (1) a relatively mild intermittent stress regimen can increase basal CORT levels and downregulate hippocampal corticosteroid receptor densities (2) a seemingly small change in housing conditions during stress appears to eliminate both receptor downregulation and increase in basal CORT levels and (3) decreased corticosteroid receptor densities at HPA feedback sites in the brain do not appear to underlie the HPA hyperresponsiveness observed in E animals.

Animals↗

Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal responses to chronic cold stress in rats.

Animals prenatally exposed to ethanol typically exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. In contrast to previous studies that have investigated effects of prenatal ethanol exposure on HPA responses to acute or intermittent stressors, our study investigated HPA responses to a chronic continuous stressor, cold stress (4 degrees C for 0, 1, or 3 days). We tested the hypothesis that prenatal ethanol exposure would result in increased plasma corticosterone (CORT) and adrenocorticotropin (ACTH) responses and increased peptide [corticotropin-releasing factor and vasopressin] mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus compared to that in control animals. In addition, CORT and ACTH responses were measured after exposure to an acute stressor (i.p. isotonic saline injection), superimposed during chronic cold exposure, to examine possible sensitization of the HPA response to the acute stress. Thus, blood samples were collected at the end of each of the three periods of cold exposure, either before (0 min) or 15 min after acute stress. The subjects were adult male and female Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment groups. Exposure to cold stress resulted in significant body weight loss in E males at 1 day and in both males and females of all prenatal treatment groups by 3 days of cold stress. Males in all prenatal groups also exhibited significant increases in adrenal weight:body weight ratios. Cold stress alone (0 min condition) increased CORT levels in E males and overall ACTH levels in E males and females compared to controls. ACTH levels were also higher overall in E compared to control males after acute stress (15 min condition). Sensitization of the CORT response to acute stress was observed in males but not females across all prenatal treatment groups. Corticotropin-releasing factor and vasopressin mRNA levels in the PVN were not significantly affected by prenatal treatment or chronic cold stress in either males or females. In contrast, both males and females displayed increases in PVN thyrotropin-releasing hormone (TRH) mRNA levels after cold stress. These data support and extend previous work demonstrating differential effects of prenatal ethanol exposure on HPA responsiveness of male and female offspring, and suggest that E males may be more vulnerable to the effects of chronic cold stress than E females.

Adrenocorticotropic Hormone↗

Glucocorticoid fast feedback is not altered in rats prenatally exposed to ethanol.

Animals exposed in utero to ethanol exhibit hormonal hyperresponsiveness to stressors in adulthood. One possible mechanism for this hyperresponsiveness is a deficit in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. The present study tested the hypothesis that a deficit in the fast feedback time domain may play a role in the hormonal hyperresponsiveness in ethanol-exposed rats. Sprague-Dawley offspring from prenatal ethanol (E), pair-fed (PF), and ad lib-fed control (C) groups were tested in two experiments. Experiment 1 used a swim stress paradigm and tested animals at the trough of the corticosterone (CORT) circadian rhythm. Experiment 2 used ether stress and tested animals at the peak of the circadian rhythm. Animals were injected subcutaneously with CORT or saline and were immediately subjected to either a 5-min swim stress or a 1-min ether stress. Half the animals were terminated immediately after stress (5-min postinjection), and the rest were terminated 25 min later. Plasma levels of CORT and ACTH were assayed to determine whether E animals differed from control animals in showing a CORT-induced blunting of the ACTH response to the stressor, indicating alterations in fast feedback regulation. Injection of CORT significantly blunted the ACTH response to swim stress (experiment 1) in E, PF, and C females and males, compared with their saline-injected counterparts. There were no significant differences among groups. Similarly, CORT-injected males in E, PF, and C groups all exhibited a significantly blunted ACTH response to ether stress (experiment 2). CORT-injected C females also exhibited a significantly blunted ACTH response to ether stress, whereas E females showed an obvious CORT decrease that approached significance. However, PF females showed a clear deficit in fast feedback regulation. Together, these data suggest that: (1) CORT injection can serve as a fast feedback signal that can blunt the ACTH response to a stressor; and (2) prenatal ethanol exposure does not produce a deficit in hypothalamic-pituitary-adrenal feedback regulation in the fast feedback time domain.

Adrenal Cortex Hormones↗

Joint surgery in Ehlers-Danlos patients: results of a survey.

The Ehlers-Danlos syndrome (EDS) is a rare, hereditary, connective-tissue disorder that results in increased laxity and poor soft-tissue healing. Surgical results and complications in these patients are not well documented in the literature. The goal of the present study was to survey patients with EDS who had surgery to the musculoskeletal system and document the results of surgery and complications. Forty-four patients with EDS were surveyed regarding the complications and results of surgical procedures to the shoulder, the elbow, the knee, or the ankle. Surgical procedures were performed for pain, instability, poor range of motion, or a combination of these, totaling 214 procedures. The population surveyed in the present study demonstrates that problems of surgical procedures in EDS may be high relative to other populations without connective-tissue disorders. More study is warranted in this patient population to validate the results in a larger cohort.

Adolescent↗

Should angiographically disease-free saphenous vein grafts be replaced at the time of redo coronary artery bypass grafting?

BACKGROUND: Controversy exists regarding the management of angiographically disease-free saphenous vein grafts at the time of redo coronary artery bypass grafting (CABG). Some authorities favor replacement of these disease-free grafts, arguing that occlusion is likely in the near future. Others believe that these grafts are "biologically privileged" and should not be replaced. METHODS: One hundred thirty-two consecutive patients (113 men, 19 women, aged 46 to 88 years, mean 67 years) underwent redo revascularization with one or more angiographically disease-free saphenous vein grafts at the time of redo CABG. Thirty-six patients had the disease-free grafts replaced (R) and 96 did not (NR). The mean interval from the first CABG was 9.25 years. RESULTS: Surgical mortality was comparable in the NR and R groups (5 of 96 or 5.2% versus 3 of 36 or 8.3%, respectively; p < 0.5). Survival at 1 and 3 years was higher in the NR group than the R group (98% versus 80%, and 95% vs. 66% respectively; p < 0.0001). Late myocardial infarction was less common in the NR group than in the R group (12 of 91 or 12.9% versus 12 of 33 or 36.4%; p < 0.003). Recurrent angina was less common in the NR than in the R group (21 of 91 or 23.1% versus 15 of 33 or 45.5%; p < 0.015). Cardiac hospitalization was required less commonly in the NR than in the R group (11 of 91 or 12.1% versus 12 of 33 or 36.4%; p < 0.002). In nondiseased grafts undergoing angiographic evaluation late after redo CABG, rate of new stenosis was lower in NR grafts than in R grafts (2 of 12 or 16.7% versus 2 of 3 or 66.7%; p < 0.05). CONCLUSIONS: With a conservative approach that does not replace nondiseased saphenous vein grafts at redo CABG (1) there is no increase in operative mortality, (2) good late survival is obtained, (3) clinical ischemia related to the NR saphenous vein grafts is uncommon, and (4) NR grafts continue to be patent. We conclude that disease-free vein grafts may not require routine replacement at redo CABG. A randomized study is required for definitive resolution.

Aged↗

Oxygen desaturations during exercise and sleep in fit tetraplegic patients.

OBJECTIVE: Tetraplegic patients are particularly at risk for respiratory deficiencies during sleep. In a previous study, it was found that several patients exhibited significant oxygen desaturations during arm ergometry tests. Therefore, the issue of whether patients who desaturate during exercise would be especially at risk for having nocturnal respiratory problems was raised. DESIGN: Respiratory recordings in connection with arm ergometry tests and during sleep. SETTING: Arm ergometry tests were performed in a hospital laboratory, and sleep recordings were performed in the patients' homes. PATIENTS: Nine C5-C6 tetraplegic patients, aged 22 to 42 years with body mass index of 15.2 to 24.2 kg/m2. MAIN OUTCOME MEASURES: Oximetry during exercise and sleep and sleep recordings. RESULTS: During exercise, six patients desaturated 6% to 20%. Only one patient had signs of a significant nocturnal respiratory problem with an average of eight desaturations per hour of sleep and an obstructive respiration movement pattern. Two additional patients (with normal oximetry during exercise) showed occasional desaturation below 89% during rapid eye movement sleep. CONCLUSION: In this study, the majority of tetraplegic patients desaturated during submaximal arm exercise but not during sleep. The reason could be that the patients in this study were all lean and physically active, which is at variance with previously published sleep studies.

Adult↗

Fetal ethanol effects on benzodiazepine sensitivity measured by behavior on the elevated plus-maze.

Rodents prenatally exposed to ethanol demonstrate altered behavioral and hormonal responses to stressful environments. Prenatal ethanol exposure may also have long-term effects on the offspring's GABAergic system. Using the elevated plus-maze, the present study examined the sensitivity of adult Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF) and ad lib-fed control (C) conditions to the effects of benzodiazepine (BZD) on plus-maze behavior and corticosterone (CORT) responses. At 60-90 days of age, E, PF, and C males and females were injected subcutaneously with either BZD or saline. Twenty minutes later animals were placed in an open field (OF) for a 5-min test and then on the plus-maze for a 5 min test; behaviors were recorded during testing and blood samples collected at the end of testing for CORT determinations. Overall, sex differences were observed in both OF and plus-maze behaviors. Females showed more ambulation and rearing in the OF than males, and exhibited increased exploratory behaviors and decreased fear-related behaviors compared to males on the plus-maze. Following BZD treatment, both males and females exhibited increased time on open arms, increased open arm entries, and decreased time on closed arms compared to saline-treated males and females, regardless of prenatal treatment. These differences did not appear to be due to altered activity levels, as BZD treatment had no effect on total ambulation in the OF. Importantly, although no significant differences in plus-maze behaviors were found among saline-injected E, PF, and C males or females. BZD treatment differentially affected E males and females compared to their PF and C counterparts. Both E males and females treated with BZD spent increased time on open arms and decreased time on closed arms compared to their PF and C counterparts, suggesting decreased fear. Further, BZD-treated E males exhibited decreased open and closed arm entries, spent significantly more time in the central area, and had lower CORT levels, another index of fear or stress, compared to BZD-treated PF and C males. These data support and extend previous work demonstrating that the plus-maze provides a reliable measure of anxiety/fear, and that plus-maze behavior is sensitive to anxiolytic agents such as BZD. Furthermore, these data suggest that prenatal ethanol exposure may alter sensitivity to the effects of BZD on plus-maze behavior and CORT responsiveness, and may do so differentially in male and females offspring.

Animals↗

Obstructive sleep apneas in relation to severity of cervical spinal cord injury.

Thirty-three subjects (28 men, five women) with complete or incomplete cervical cord injury representing a wide range of neurological impairment were investigated with regard to the prevalence of Obstructive Sleep Apnea (OSA). The relation between OSA and neurological function, respiratory capacity, body mass index and symptoms associated with OSA were studied. Overnight sleep recordings employed combined oximetry and respiratory movement monitoring. Pulmonary function tests included static and dynamic spirometry, maximal static inspiratory and expiratory pressures at the mouth. The subjects answered a questionnaire concerning sleep quality and tiredness. The prevalence of OSA was 15% (5/33) in this nonobese cervical cord injury study population. Nine percent of the subjects (3/33) fulfilled the criteria for obstructive sleep apnea syndrome, but daytime sleepiness or fatigue were also common in subjects without OSA. There was an inverse correlation between oxygen desaturation index and American Spinal Injury Association (ASIA) motor score in the subjects with complete injury, while there was no such correlation in the whole study group. There were significant correlations between maximal inspiratory and expiratory pressures and vital capacity and between ASIA motor score and vital capacity.

Adult↗

Voluntary activation of the human diaphragm in health and disease.

Intersubject comparison of the crural diaphragm electromyogram, as measured by an esophageal electrode, requires a reliable means for normalizing the signal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high and reproducible diaphragm electromyogram root-mean-square (RMS) values and 2) to determine the relative diaphragm activation and mechanical and ventilatory outputs during breathing at rest in healthy subjects (n = 5), in patients with severe chronic obstructive pulmonary disease (COPD, n = 5), and in restrictive patients with prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher during inspiration to total lung capacity than during sniff inhalation through the nose (P = 0.035, ANOVA). The RMS (percentage of voluntary maximal RMS) during quiet breathing was 8% in healthy subjects, 43% in COPD patients, and 45% in PPI patients. Despite the large difference in relative RMS (P = 0.012), there were no differences in mean transdiaphragmatic pressure (P = 0.977) and tidal volumes (P = 0.426). We conclude that voluntary maximal RMS is reliably obtained during an inspiration to total lung capacity but a sniff inhalation could be a useful complementary maneuver. Severe COPD and PPI patients breathing at rest are characterized by increased diaphragm activation with no change in diaphragm pressure generation.

Adult↗

The hormonal effects of alcohol use on the mother and fetus.

During pregnancy, the hormonal systems of the mother and fetus are intricately interconnected to ensure normal fetal development. Accordingly, maternal alcohol consumption during pregnancy can interfere with fetal development, not only directly, through adverse effects exerted by alcohol that crosses the placenta and enters the fetal bloodstream, but also indirectly, by disturbing the functions and interactions of maternal and fetal hormones. In both the mother and the fetus, alcohol exposure can impair the functioning of the hypothalamic-pituitary-adrenal axis, which regulates the body's response to stress; the hypothalamic-pituitary-gonadal axis, which controls reproductive functions; and the hypothalamic-pituitary-thyroid axis, which regulates the metabolism of almost all tissues. In addition, alcohol can interfere with the activities of growth hormone and insulin-like growth factors, which promote body growth and activity. Some of the effects of maternal alcohol consumption on fetal hormone systems may contribute to the adverse effects observed in children with fetal alcohol syndrome and related disorders.

Alcohol Drinking↗

Influence of ethanol consumption on immune competence of adult animals exposed to ethanol in utero.

Ethanol consumption results in significant changes in the immune system of experimental animals and humans. Previous work by ourselves and others has established that in utero exposure to ethanol results in alterations in the immune system of the offspring that persist into adult life. The present study was designed to determine if prenatal exposure to ethanol results in increased vulnerability to the immunosuppressive effects of ethanol consumption in adulthood. Male and female Sprague-Dawley offspring were selected in adulthood from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups, and given either an ethanol-containing liquid diet or were pair-fed an isocaloric liquid diet without ethanol for 30 days. At the end of the 30-day feeding period, lymphocyte responses to the mitogens concanavalin A (Con A) and lipopolysaccharide, and to interleukin-2 (IL-2) were tested using in vitro assays. The results of this study support and extend previous data demonstrating long-term adverse effects of prenatal ethanol exposure on T-cell responses to mitogens, and provide further evidence that deficits seem to be more robust in male than in female offspring. Prenatal E males showed reduced T-lymphocyte proliferation to Con A and T-lymphoblast proliferation to IL-2, compared with their prenatal PF and C counterparts, regardless of whether they were exposed to the ethanol or the control diet in adulthood. In addition, T-lymphoblast proliferation to IL-2 was suppressed in prenatal E, compared with prenatal C, females exposed to control diet in adulthood. This is the first report of a deficit in T-cell aspects of immunity in E females, although it appears that this deficit may have been partially mediated by nutritional effects. A second major finding in this study is that consumption of ethanol diet in adulthood in itself had significant immunosuppressive effects on T-cell responses in both males and females. However, contrary to our expectation, previous exposure to ethanol in utero did not exacerbate the changes in immune responsiveness that were observed after adult ethanol consumption.

Alcoholism↗

Prenatal ethanol exposure differentially alters behavior in males and females on the elevated plus maze.

Rodents prenatally exposed to ethanol demonstrate hypothalamic-pituitary-adrenal and behavioral hyperactivity to a variety of stressful situations. The present study examined both behavioral and corticosterone (CORT) responses to the elevated plus maze (+-maze), an anxiety- or fear-provoking task. Sprague-Dawley male and female offspring from fetal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were tested at 60 to 90 days of age. In experiment 1, behavior was measured in animals exposed to the +-maze for 5 min on two consecutive days; 2 weeks later, both behavioral and CORT responses were measured in animals confined to the open and closed arms of the maze for 20 min. In experiment 2, animals were placed in an open field (OF) for 5 min before a single 5-min exposure to the +-maze. Factor analysis of the scored behaviors from the two experiments indicated two main factors, designated "exploration" and "fear." E males and females both exhibited higher levels of exploratory behaviors when placed directly on the +-maze from their homecages without prior exposure to the OF, compared with C males and females. In addition, when confined to the closed arms of the +-maze, E males and females demonstrated higher levels of activity, compared with C males and females. After OF exposure, however, both E males and females demonstrated lower levels of exploratory behaviors than C males and females, and E females also had increased CORT levels, compared with PF and C females. Interestingly, E females, but not E males, showed an increase in fear-related behaviors on the +-maze, compared with controls, regardless of prior OF exposure. These data demonstrate that prenatal ethanol exposure may differentially affect both behavioral and hormonal responses of males and females in an aversive behavioral task and suggest that there may be a sex difference in the sensitivity of the mechanism(s) underlying these responses.

Animals↗