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Biomedical subjects

G Winkel

Publications and source records attributed to G Winkel.

7 recordsLinked to original sources

Social support, intrusive thoughts, and quality of life in breast cancer survivors.

This study explores the moderating effect of social support on the relationship between cancer-related intrusive thoughts and quality of life. Sixty-four breast cancer survivors completed self-report measures of appraisal social support (the disclosure of thoughts and feelings to significant others), cancer-related intrusive thoughts, and quality of life. Controlling for demographic and treatment variables, the negative impact of cancer-related intrusive thoughts on both physical and mental quality of life measures was moderated by appraisal social support. For women with high levels of appraisal support, cancer-related intrusive thoughts had no significant relationship with quality of life. However, for women with low levels of appraisal support, the relationship between cancer-related intrusive thoughts and quality of life was significant and negative. These results suggest that appraisal social support can mitigate the impact of traumatic life events.

Adult↗

Suppression of apoptosis by glucocorticoids in glomerular endothelial cells: effects on proapoptotic pathways.

Tumour necrosis factor-alpha (TNF-alpha)- and lipopolysaccharide (LPS)-induced apoptosis of bovine glomerular endothelial cells is now recognized as an important part in the pathogenesis of glomerulonephritis characterized by early mitochondrial cytochrome c release, mitochondrial permeability transition, Bak protein upregulation, Bcl-X(L) protein downregulation and caspase-3 activation. Co-treatment of cells with 10 nM dexamethasone and TNF-alpha or LPS blocked roughly 90% of apoptotic cell death in glomerular endothelial cells. The action of glucocorticoids could be documented in that they prevented all apoptotic markers such as DNA laddering, DNA fragmentation measured by the diphenylamine assay as well as morphological alterations. To mechanistically elucidate the action of glucocorticoids we evaluated whether glucocorticoids elicit a time-dependent effect. For dexamethasone, to maximally inhibit DNA fragmentation a preincubation period was not required. Even if dexamethasone was supplemented 6 h following TNF-alpha or LPS we observed a maximal inhibitory effect. Concerning its influence on TNF-alpha and LPS signal transduction, we found that dexamethasone only partially prevented cytochrome-c-release as a first sign of apoptotic cell death but efficiently blocked mitochondrial permeability transition. Moreover, TNF-alpha- and LPS-induced Bak upregulation, Bcl-X(L)-downregulation, and the activation of caspase-3-like proteases, measured fluorometrically using DEVD-AMC and PARP cleavage, were efficiently blocked by dexamethasone. We postulate that glucocorticoids exert their inhibitory action upstream of the terminal death pathways but downstream of primary receptor mediated signals by blocking pro-apoptotic signals pre- and/or post cytochrome c release and mitochondrial signalling.

Animals↗

Housing status and health care service utilization among low-income persons with HIV/AIDS.

OBJECTIVE: To examine the impact of housing status on health service utilization patterns in low-income HIV-infected adults. DESIGN: A survey of 1,445 HIV-infected Medicaid recipients in New York State between April 1996 and March 1997. MAIN RESULTS: Six percent of study participants were homeless, 24.5% were "doubled-up," and 69.5% were stably housed. Compared with the stably housed, doubled-up and homeless participants were less likely to be seeing a physician regularly (P = .0001), and if seeing a physician, they were likely to have been doing so for a significantly shorter time (P = .02). The homeless were also less likely than either stably housed or doubled-up individuals to see the same physician or group of physicians at each ambulatory visit (P = .007). In addition, a higher proportion of the homeless had made one or more hospital visits over the prior 3 months than the nonhomeless. After multivariate adjustment, doubled-up participants were found to make more emergency room visits, the homeless were less likely to be taking prophylaxis for Pneumocystis carinii pneumonia, and both the doubled-up and the homeless were shown to use slightly more outpatient care than the stably housed. CONCLUSION: Our study documents differences in health care utilization patterns across stably housed, doubled-up, and homeless HIV-infected persons after controlling for health insurance coverage. These differences, especially those pertaining to outpatient services, suggest that the unstably housed may be receiving less adequate health care than the stably housed, and hence may be more likely to experience adverse clinical outcomes.

Adult↗

The role of prophylactic cholecystectomy during splenectomy in children with hereditary spherocytosis.

BACKGROUND/PURPOSE: Hereditary spherocytosis is an autosomal dominant disorder associated with an intrinsic defect in the red blood cell membrane often necessitating splenectomy to prevent sequestration of spherocytes. When cholelithiasis is present, these patients undergo cholecystectomy at the same surgical setting as splenectomy. After splenectomy alone, it is uncertain whether the amount of hemolysis is adequately decreased to prevent subsequent gallstone formation. This study set out to evaluate the frequency in which symptomatic cholelithiasis subsequently develops in children treated by splenectomy alone. METHODS: All patients less than 18 years old with hereditary spherocytosis who underwent splenectomy without cholecystectomy at our institution during the past 27 years were included in this study. A retrospective chart review and telephonic patient follow-up was performed. Gallstones were excluded in these patients either by preoperative ultrasound scan, or by intraoperative palpation of the gallbladder. The main study outcomes of this group included documented cases of cholelithiasis, subsequent need for cholecystectomy secondary to cholelithiasis, and questionnaire to determine the incidence of "subclinical" cholelithiasis (not reported to a physician). RESULTS: Twenty-three subjects were identified who met the inclusion criteria. Complete follow-up data were obtained for 17 of these patients (74%). The mean age at splenectomy was 6.6 +/- 0.69 years, and the mean follow-up was 15.65 +/- 2.03 years (median, 18 years). None of the patients in this series subsequently have undergone cholecystectomy, nor have any had either clinical or subclinical evidence of cholelithiasis since splenectomy. CONCLUSION: Prophylactic cholecystectomy at the time of splenectomy is not indicated in patients with hereditary spherocytosis who do not have gallstones.

Adolescent↗

Glucocorticoids potently block tumour necrosis factor-alpha- and lipopolysaccharide-induced apoptotic cell death in bovine glomerular endothelial cells upstream of caspase 3 activation.

1. Endothelial cell damage in glomeruli and kidney arterioles appears to play a pivotal role in glomerular inflammatory diseases. Glomerular endothelial cells, a specialized microvascular cell type involved in the regulation of glomerular ultrafiltration, die by apoptosis in response to tumour necrosis factor-alpha (TNF-alpha), TNF-alpha/basic fibroblast growth factor (bFGF), TNF-alpha/cycloheximide, and bacterial lipopolysaccharide (LPS). Apoptotic cell death is characterized by extensive DNA cleavage, DNA ladder formation, and characteristic morphological alterations. 2. In search for apoptosis-preventing signals, we identified glucocorticoids as potent death preventing factors. Co-treatment of cells with 10 nM dexamethasone and TNF-alpha, TNF-alpha/bFGF, TNF-alpha/cycloheximide, or LPS blocked roughly 90% of apoptotic cell death in glomerular endothelial cells. 3. Similarly to dexamethasone (TNF-alpha- and LPS-induced apoptosis are prevented with IC50 values of 0.8 and 0.9 nM, respectively), other synthetic and natural forms of glucocorticoids, such as fluocinolone, prednisolone, hydrocortisone, and corticosterone potently inhibited cell death with IC50 values of 0.2, 6, 50 and 1000 nM, for TNF-alpha and 0.7, 8, 100 and 500 nM for LPS, respectively. 4. Apart from glucocorticoids, mineralocorticoids such as aldosterone also blocked TNF-alpha/LPS-induced apoptosis (IC50 approximately 500 nM for TNF-alpha and approximately 500 nM for LPS), whereas sex hormones, i. e. beta-estradiol and testosterone remained without effect. 5. The protective effect of glucocorticoids (and mineralocorticoids) required glucocorticoid receptor binding as it could be antagonized by the glucocorticoid receptor antagonist RU-486. Concerning TNF-alpha and LPS signal transduction, we found that dexamethasone efficiently prevented TNF-alpha- and LPS-induced activation of caspase-3-like proteases. Therefore, we postulate inhibitory mechanisms upstream of terminal death pathways.

Animals↗

Global meaning and psychological adjustment among survivors of bone marrow transplant.

The purpose of the present study was to examine global meaning (i.e. the belief that life has purpose and coherence) and psychological adjustment in survivors of bone marrow transplantation (BMT). Eighty-five survivors of BMT participated in a telephone interview. Regression analyses demonstrated that after controlling for physical functioning, stressor severity, and gender, global meaning was inversely related to global psychological distress and BMT-related psychological distress (i.e. posttraumatic stress disorder-like symptoms related to the cancer treatment). Global meaning was also positively related to mental health aspects of quality of life (e.g. emotional functioning and social functioning). These findings suggest that global meaning may be an important factor in the psychological adjustment of BMT survivors.

Adaptation, Psychological↗