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Biomedical subjects

J Weinberg

Publications and source records attributed to J Weinberg.

At least 235 records · Page 13Linked to original sources

Interactive effects of ethanol intake and maternal nutritional status on skeletal development of fetal rats.

Skeletal development on gestation day 21 was examined in fetuses of alcohol-consuming (A), pair-fed (PF) and ad lib-fed (C) Sprague-Dawley females. Ethanol (36% ethanol-derived calories) was administered in liquid diets that were marginal (Diet A1) or optimal (Diet A2) in terms of pregnancy requirements (18% vs. 25% total calories as protein, respectively). For each bone studied, a lengthwise measurement was made of the whole bone and of the ossified portion(s), and percent ossification was calculated. Number of sternebral ossification centers present was also determined. Alcohol-exposed fetuses showed retarded ossification of the tibia and radius, regardless of maternal protein intake. Increasing the protein content of the alcohol diet from 18% (Diet A1) to 25% (Diet A2) significantly increased ossification of the ulna, sternum, humerus and ilium-ischium. For the ulna, A2 fetuses showed greater ossification than A1 fetuses but were still retarded compared to PF and C fetuses. For the sternum, humerus and ilium-ischium, however, ossification in A2 fetuses increased to the levels observed in the PF and C groups. In addition, number of sternebral ossification centers present was significantly increased in A2 compared to A1 fetuses. These data indicate that skeletal development provides a sensitive index of ethanol-induced developmental delay as well as interactive effects of ethanol and nutrition.

Animals↗

Prenatal ethanol exposure alters adrenocortical response to predictable and unpredictable stressors.

In the present study, effects of psychological stressors and stressor predictability on the adreno-cortical responses of animals exposed to ethanol in utero were examined. Male and female offspring from ethanol-exposed (E), pair-fed (PF), and ad lib-fed control (C) conditions were tested in adulthood. Separate sets of animals were exposed once daily for 5 consecutive days to either unpredictable (UNPRED) or predictable (PRED) restraint stress or to UNPRED novelty stress. On the fifth test day, blood samples for plasma corticosterone determination were taken either prior to stress (basal levels) or following stress. Males in all groups and C females had higher basal corticosterone levels if previously subjected to PRED restraint than if previously subjected to UNPRED restraint; E and PF females did not exhibit this differential responsiveness. Following restraint stress on the fifth test day, there were no significant differences in response to PRED and UNPRED restraint among E, PF, and C males. In contrast, C but not E or PF females exhibited a greater plasma corticosterone response to UNPRED than to PRED restraint. Following novelty stress, E males exhibited a significantly reduced plasma corticosterone response compared to PF and C males. For females, there was a trend for an increased corticoid response in E compared to PF females following novelty stress as well as a different pattern of response among groups from days 1 to 5 of testing. These data support and extend previous studies suggesting that, compared to PF and C animals, E animals may exhibit altered responses to stressors as well as deficits in the ability to use or respond to environmental cues.

Animals↗

Prenatal ethanol effects: sex differences in offspring stress responsiveness.

Previous studies have shown that offspring prenatally exposed to ethanol are hyperresponsive to stressors in adulthood, and have suggested that females are typically more affected than males. The present study was undertaken to investigate further this apparent sex difference in prenatal ethanol effects on stress responsiveness. Male and female offspring from prenatal ethanol-exposed (E), pair-fed (PF), and ad lib-fed control (C) conditions were tested in adulthood to determine adrenocortical responses to a prolonged (4-h) restraint stress. There were no significant differences in corticoid responsiveness among females from the three treatment groups. All females showed a marked increase in plasma corticosterone at 30 min, and corticoid levels remained elevated through 150-min restraint. By 180 min, all females showed a significant corticoid decrease, although corticosterone remained elevated over basal levels throughout the 240-min stress period. For males, in contrast, there were significant differences among groups. All males showed a significant corticoid increase over basal levels at 30 min, and corticoids remained significantly elevated through 90-min restraint. By 120 min, PF and C males showed a significant corticoid decrease although corticoids never returned to basal levels during the 240-min restraint period. E males, however, showed no significant decrease from peak corticosterone levels throughout the 240-min restraint stress. These data indicate that pituitary-adrenal hyperresponsiveness is not limited to fetal ethanol-exposed females, but may be demonstrated in fetal ethanol-exposed males under appropriate conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Early handling can attenuate adverse effects of fetal ethanol exposure.

The effects of early handling on physiological and hormonal responses of rats exposed to ethanol prenatally were studied. Male and female Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad lib-fed control (C) prenatal treatment groups were either handled (H) or nonhandled (NH) during the preweaning period and tested in adulthood. Early handling eliminated the deficit in preweaning weight gain observed in E compared to PF and C offspring. In adulthood, early handling eliminated the increased hypothermia observed in E and PF compared to C males following an ethanol challenge (2.0 g/kg, IP). In addition, H males displayed marginally less hypothermia overall than NH males. In contrast, handling accelerated the return to preinjection temperature in PF and C females but had no effect on E females. There were no significant differences among E, PF, and C rats in corticosterone (CORT) responses to ethanol challenge (1.5 g/kg, IP), but both males (marginally) and females in the H condition displayed higher CORT levels overall than NH rats. Early handling also eliminated the increased peak CORT response to restraint stress in E compared to C females, but did not affect the more prolonged elevation of CORT in E compared to PF and C females. There were no differences among E, PF, and C females in hippocampal type I and type II glucocorticoid receptor density or affinity. However, binding affinity of type II receptors was slightly but significantly increased in H compared to NH females. Together, these data indicate that early handling may modulate or attenuate some, but not all, of the adverse effects of fetal ethanol exposure on offspring growth and physiological responsiveness.

Animals↗

Effects of prenatal ethanol exposure and postnatal handling on conditioned taste aversion.

Studies have shown that animals prenatally exposed to ethanol (E) exhibit deficits in conditioned taste aversion as well as displaying hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness during exposure to stressors. In contrast, postnatal handling has been shown to attenuate both emotional and HPA reactivity under certain conditions. The present study tested the hypothesis that handling could attenuate adverse effects of prenatal ethanol exposure on consummatory behavior and HPA activity in a conditioned taste aversion task. We found that both prenatal ethanol exposure and handling independently increased saccharin consumption over 5 days of pretoxicosis exposure, suggesting that neophobia decreased at a faster rate in these animals. When conditioned aversion was assessed in handled animals under nondeprived conditions, E animals showed increased consumption compared to controls. Furthermore, across prenatal groups, lower corticosterone (CORT) levels were found in handled compared to nonhandled animals during reexposure under food-deprived conditions, emphasizing the importance of assessing both behavior and HPA function when examining an animal's response to a task and indicating that handling may not be effective at attenuating some deficits in E animals.

Animals↗

Psychosocial stressors and mammary tumor growth: an animal model.

Stressful life events and the ability to cope with stress may play a role in the progression of breast cancer; however, the complex relationship between stressors and tumor growth is difficult to investigate in humans. Our studies have utilized the androgen-responsive Shionogi mouse mammary carcinoma (AR SC115) in male mice to investigate the effects of social housing condition on tumor growth rates and responses to chemotherapy. We demonstrate that, depending on social housing condition, mammary tumor growth and response to chemotherapy can both increase and decrease. We have examined the possible role(s) of 1) psychosocial variables, 2) testosterone and corticosterone, hormones altered by stress and known to stimulate SC115 cells in vivo and in vitro, 3) NK cells, one of the body's first lines of defense against tumor cells, 4) stress proteins, in mediating the differential tumor growth rates observed in our model. This review discusses the investigations we have undertaken to elucidate the mechanisms through which a psychosocial stressor, social housing condition, can alter tumor growth rate.

Animals↗

Influence of plate design on cortical bone perfusion and fracture healing in canine segmental tibial fractures.

OBJECTIVE: To investigate whether or not the limited contact design of the low-contact dynamic compression plate (LCDCP) provides advantages over the dynamic compression plate (DCP) in the context of cortical bone blood flow, biomechanical properties, and remodeling of bone in segmental tibial fractures. DESIGN: Randomized trial using canines. SETTING: Animal research laboratory. PARTICIPANTS: Eleven canines. INTERVENTION: Segmental tibial fractures were surgically created in canine tibiae. The tibiae were reduced and stabilized with 316L stainless-steel, 3.5-millimeter, ten-hole plates: LCDCP (n = 5) or DCP (n = 6). MAIN OUTCOME MEASUREMENTS: Laser Doppler flowmetry evaluated cortical bone perfusion in the proximal tibia, segmental piece, and distal tibia (a) before fracture, (b) after fracture, (c) immediately after plating, and (d) at ten weeks. After the dogs were killed at ten weeks, bending stiffness and load to failure of the tibiae were assessed. Tibial cortical bone porosity and new bone formation were measured. RESULTS: Cortical bone blood flow was similar between the LCDCP and DCP groups throughout the study. Bending stiffness and load to failure of the tibiae were similar between the two groups. Whereas cortical bone porosity and new bone formation were higher in all plated tibiae at ten weeks compared with controls, no differences in cortical bone porosity were seen between the LCDCP and DCP groups. There was a trend toward significantly more new bone formation in the LCDCP group. CONCLUSION: The LCDCP is not advantageous in fracture healing or restoration of cortical bone perfusion to devascularized cortex in segmental fractures when plate fixation has been chosen for fracture stabilization. The overall injury following segmental devascularization seems more important to outcome than the type of implant used for fracture fixation up to ten weeks.

Animals↗

Effects of social housing condition on chemotherapeutic efficacy in a Shionogi carcinoma (SC115) mouse tumor model: influences of temporal factors, tumor size, and tumor growth rate.

OBJECTIVE: The objective of this study was to investigate 1) whether social housing condition, tumor size, and tumor growth rate alter responses to chemotherapy and 2) whether the timing of tumor cell injection or chemotherapy initiation (relative to housing condition formation) influences tumor growth rate or the efficacy of chemotherapy. METHODS: Mice were reared individually (I) or in groups (G). In experiment 1, mice were rehoused (IG or GI) or left in group housing (GG) immediately after tumor cell injection. In experiment 2, housing conditions (II, IG, GG, or GI) were formed when tumors weighed 1 g. Chemotherapy (adriamycin 4 mg/kg and cyclophosphamide 61.5 mg/kg IP) and exposure to acute novelty stress (15 min/d, 5 d/wk) were initiated 1 day after housing condition formation. RESULTS: If chemotherapy was initiated when the tumor burden was undetectable (experiment 1), housing condition did not alter tumor response to chemotherapy, although IG mice lost the most weight and overall had the lowest probability of survival. If chemotherapy was initiated when tumors weighed 1 g (experiment 2), both tumor and host responses to chemotherapy were poorest for IG mice. Timing of tumor cell injection relative to housing condition formation also differentially influenced the rate of tumor growth in mice treated with the drug vehicle; in experiment 1, tumor growth rate was faster in GI and GG mice than in IG mice, whereas in experiment 2, the rate of tumor growth was faster in II mice than in GG and IG mice. CONCLUSIONS: Altering the temporal relationships among social housing condition formation, tumor cell injection, and chemotherapy initiation differentially influences the rate of tumor growth and the efficacy of chemotherapy. Effects of housing condition are independent of tumor growth rate at chemotherapy initiation and, in terms of host responses, independent of tumor burden.

Animals↗

Effects of ethanol and maternal nutritional status on fetal development.

This study investigated the interactive effects of alcohol and nutritional status of the pregnant female on fetal growth and development. Three liquid diets were formulated ranging in protein content from suboptimal to supraoptimal: diet I provided 18% kcal as protein and 1.0 kcal/ml; diets II and III provided 25 and 32% kcal, respectively, as protein and 1.2 kcal/ml. In all cases, alcohol provided 36% of total calories. Both pair-fed and ad libitum fed control groups were included. We found that blood alcohol levels were consistently high in all three diet regimens throughout gestation. Alcohol intake suppressed weight gains and increased adrenal weights and placenta weights in pregnant females. Both body weights and brain weights were reduced in alcohol-exposed fetuses. However, relative brain weights were found to be increased in alcohol fetuses, indicating "brain sparing." Maternal nutritional status had no major effect on developmental outcome. Thus, with alcohol administered as a high proportion of total daily calories, increasing dietary protein levels did not attenuate the major adverse effects of alcohol on fetal development.

Adrenal Glands↗

Polysomnography in chronic neuromuscular disease.

BACKGROUND: Sleep is a risk factor for respiratory failure in patients with chronic neuromuscular diseases (NMD). OBJECTIVE: To explore the diagnostic value of monitoring sleep parameters in addition to nocturnal respiratory parameters. METHODS: Thirty-one patients with chronic NMD underwent whole-night polysomnograms including EMG from accessory respiratory muscles. RESULTS: Sleep macrostructure was normal on average. The number of respiratory arousals per hour of sleep was above the upper limit observed in a control group (>2.1) in 71% of the patients, but was moderate in most cases. Nadir oxygen saturation <85% was the most common finding indicating respiratory dysfunction and was present in 80% of the patients. Noninvasive blood gas monitoring identified all but 2 patients with respiratory-induced sleep abnormalities. The respiratory arousal rate was correlated with the oxygen desaturation index, but otherwise there were no significant correlations between sleep and nocturnal respiratory parameters. Vital capacity was significantly positively correlated with obstructive apnea index and daytime base excess to nadir oxygen saturation. Inspiratory activity in accessory respiratory muscles was present during REM sleep and/or slow wave sleep in 70% of the patients. CONCLUSION: The severity of nocturnal respiratory dysfunction is not reflected in the extent of sleep impairment in patients with chronic neuromuscular diseases.

Adult↗

Occult presentation of myotonia congenita in a 15-year-old athlete.

A case of myotonia congenita in an adolescent athlete was presented. Although this is a rare condition unknown to many treating physicians, the key to diagnosis was provocation of the patient's symptoms of muscle "tightening" and "cramping" during sustained exercise. The diagnosis would have been missed in routine office examinations with the patient at rest. The stereotypic generalized myotonic signs and symptoms were provoked after the patient was asked to play 20 minutes of basketball during one of his office evaluations. The provocative or postexercise examination was critical to the diagnosis as the resting office examination was completely normal. The diagnosis was subsequently confirmed by EMG and genetic testing. Myotonia congenita should be considered in the differential diagnosis of athletes with exercise-induced muscle "stiffness" or "cramping," particularly if the course is protracted and initial examinations are unremarkable. A provocative exercise period can be used to make the diagnosis. Once the diagnosis is established, appropriate pharmacologic treatment may improve symptoms and allow return to daily activity without restriction.

Adolescent↗

Medicare beneficiary complaints about quality of care.

This study examined all Medicare beneficiary complaints about quality of care submitted to the California Peer Review Organization (PRO) over 18 months. The complaint rate was low, and a medical record review by the PRO only confirmed 13% of the complaints. Managed Care Organization (MCO) members filed significantly more complaints about denial and/or delays in receiving services and the failure to refer to specialists. Fee-for-service complaints focused on inpatient hospital services, particularly premature discharge, discharge planning, admission necessity, and unnecessary tests. The PRO review process took over 7 months, and the findings were generally not released to the complainants.

Aged↗

Synthesis and molecular mechanical studies of antiviral copper(II) complexes with morpholinebiguanide drug.

The synthesis and characterization of new Cu(II) complexes with morpholinebiguanide drug are described. The complexes formed have been characterized by elemental analysis, IR, UV-VIS, conductance measurements, EPR spectra and magnetic susceptibility measurements. Their biological activity is supported by the experimental data and enhanced by the theoretical ones. The morpholinebiguanide ligand and their copper(II)-complexes were studied by molecular mechanics program.

Antiviral Agents↗

A cost-effective particle agglutination assay to detect viral antibodies in dried blood spots--a simple solution to HIV and HCV screening.

OBJECTIVES: To conduct a serological survey of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in Gabon and Ga-Rankuwa, South Africa. A secondary objective was to test a novel, simple, inexpensive agglutination assay for anti-HIV IgG and anti-HCV IgG from blood samples stored as spots dried onto filter paper. DESIGN: Blood from heel pricks was dried onto filter paper and stored. Blood was eluted from the spots and serum antibody was then assayed using a modified agglutination assay--blood was added to gelatin agglutination beads that had been sensitised with viral antigen. A positive result showed as an agglutination pattern while a negative result appeared as a tight bead. SUBJECT: This was a hospital-based study involving 271 neonates at Ga-Rankuwa Hospital, South Africa, and 856 patients ranging in age from three months to over 50 years who attended clinics in Gabon. RESULTS: Seroprevalence to HIV was determined in Ga-Rankuwa to be just under 14% (13.8%). Antibodies to HCV were not detected. In Gabon, the prevalence to HIV was just under 1% (0.82%) with a relatively high incidence of HCV, nearing 4% (3.79%). CONCLUSION: The sensitivity of the agglutination assay compared favourably to enzyme immune assay (EIA) with respect to sensitivity, simplicity and cost. This assay may be useful in sero-epidemilogical assays in developing countries.

Adolescent↗