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Biomedical subjects

H Volk

Publications and source records attributed to H Volk.

At least 19 recordsLinked to original sources

Immunological dysregulation of lung cells in response to vitamin E deficiency.

Vitamin E supplementation exhibits anti-inflammatory properties. In the lung, the beneficial effects of vitamin E supplementation on inflammation and infections are well documented, but potential consequences of alimentary vitamin E deficiency to the immunological status of lung cells are not known. It is unclear if temporary vitamin E deficiency exhibits deleterious consequences or can be compensated for by other cellular antioxidants. To address this question, the alimentary vitamin E supply to rats was modified. We then investigated the effects on major histocompatibility molecule (MHC) class II, cell adhesion molecules, interleukin (IL)10, tumor necrosis factor (TNF)alpha in various lung cells. The constitutive expression of MHC class II, intercellular adhesion molecule (ICAM)-1, L-selectin, alpha5-integrin, and CD 166, was demonstrated by flow cytometry on type II pneumocytes, alveolar macrophages, and on co-isolated lymphocytes. Vitamin E depletion increased ICAM-1 and CD166 on type II cells and macrophages, whereas the expression of L-selectin increased only on macrophages. Furthermore, the vitamin E depletion increased the cellular content and secretion of IL10 in type II cells, but decreased the content and secretion of TNFalpha. Vitamin E depletion decreased the cellular vitamin E content, but did not change the activity of antioxidant enzymes (catalase, superoxide dismutase) and the glutathion (GSH)/oxidized glutathion (GSSG) ratio in alveolar type II cells. The shift of protein kinase C (PKC) from the cytosol to membranes indicates that a PKC-dependent signaling pathway may be involved in the change of the immunological status of type II cells. All these effects were reversed by vitamin E repletion. In summary, these results are clearly compatible with the view that a temporary vitamin E deficiency induces a reversible immunological dysregulation in alveolar type II cells and lung macrophages. This deficiency might predispose the lung to develop acute or chronic inflammation.

Animals↗

Catecholamines trigger IL-10 release in acute systemic stress reaction by direct stimulation of its promoter/enhancer activity in monocytic cells.

Acute stress reactions (e.g. linked with trauma, major surgery, psychic stress and myocardial infarction) are accompanied with temporary systemic release of the anti-inflammatory cytokine IL-10 followed by immunodepression. Since an association between activation of the sympathetic system and IL-10 release has been described, we studied the influence of catecholamines on its promoter activity in vitro. Using reporter gene assays we demonstrated that catecholamines in monocytic cells directly stimulate the IL-10 promoter/enhancer via a cAMP/protein kinase A-dependent pathway. A cAMP responsive element was identified as major target. Thus, catecholamines are directly involved in the regulation of immunoresponsiveness under stressful conditions.

Catecholamines↗

Comparison of monocyte functions after LPS- or IL-10-induced reorientation: importance in clinical immunoparalysis.

Immunoparalysis is an acquired immunodeficiency which may occur in patients after major surgery, burns, polytrauma and sepsis. It is associated with a modified state of monocytes marked by their altered capacity to induce antigen-specific T cell stimulation and to release various cytokines. However, the pathogenesis of immunoparalysis may differ in various patient groups. It can develop in patients after systemic hyperinflammation induced by gastrointestinal translocation of endotoxin (lipopolysaccharide, LPS) or sepsis, as well as in patients without preceding systemic inflammation but primary anti-inflammation, for instance induced by sympathetic activation. To further elucidate the syndrome, we compared endotoxin tolerance as a model of immunoparalysis after systemic hyperinflammation versus interleukin-10 (IL-10) treatment as a model of primarily anti-inflammation-induced immunoparalysis. In vitro priming of peripheral blood mononuclear cells with either LPS or IL-10 for 24 h led to a strongly or moderately diminished LPS-induced tumor necrosis factor-alpha (TNF-alpha) production, compared to unprimed controls, respectively. Furthermore, LPS-induced reduction of TNF-alpha production capacity persisted over the following days whereas IL-10-primed monocytes rapidly recovered. Similarly, in contrast to persistently diminished MHC class II expression in LPS-treated monocytes, IL-10 only transiently downregulated these molecules. Consequently, in contrast to IL-10-primed monocytes, LPS-primed monocytes were greatly impaired in their capacity to induce antigen-specific T cell proliferation and IFN-gamma production. These data indicate that LPS priming provokes a more profound modulation of monocyte function than IL-10 priming, raising the question of possible variations in the clinical course of immunoparalysis, dependent on its pathogenesis.

Antigen Presentation↗

Measurement of anti-human cytomegalovirus T cell reactivity in transplant recipients and its potential clinical use: a mini-review.

By allowing direct determination of the frequencies of antigen-specific memory T cells in peripheral blood, novel techniques based on flow cytometry provide new diagnostic opportunities in various clinical settings, including organ transplantation. While the importance of the T cell compartment for the anti-human cytomegalovirus (HCMV) immune response is undisputed, efficient monitoring of this response was previously impossible because the conventional methods for measuring CD4+ and CD8+ T cell responses are too time-consuming and cost-intensive. We analyzed how the rapid induction of anti-HCMV CD4+ and CD8+ memory T cells by HCMV viral lysate or HCMV-derived peptides, respectively, followed by a flow-cytometric detection step, may be used to monitor HCMV-specific CD4+ and CD8+ memory T cells in solid-organ recipients. We also discuss a number of preconditions for integrating such testing into the clinical routine.

CD4-Positive T-Lymphocytes↗

Increased bloodstream infection rates in surgical patients associated with variation from recommended use and care following implementation of a needleless device.

OBJECTIVE: To determine if an apparent increase in bloodstream infections (BSIs) in patients with central venous catheters (CVCs) was associated with the implementation of a needleless access device. DESIGN: Retrospective cohort study using a derived CVC-days factor for estimating appropriate denominator data. SETTING: A 350-bed urban, acute, tertiary-care hospital. METHODS: BSI surveillance data were obtained, and high-risk areas for BSIs were determined. A random 5% sample of medical records was used to estimate CVC days, and a cohort study was conducted to compare BSI rates before and during needleless device use. A survey was conducted of nursing needleless-device practices. RESULTS: The surgical intensive-care unit (SICU), the medical intensive-care unit, and the solid organ transplant unit (OTU) were identified as high-risk units. Using existing surveillance BSI data and the estimated CVC days, the catheter-related BSI rates in the high-risk surgical patients were significantly higher during the needleless-device period compared with the preneedleless-device period (SICU, 9.4 vs 5.0/1,000 CVC days; OTU, 13.6 vs 2.2/1,000 CVC days). A survey of the nurses revealed that 60% to 70% were maintaining the needleless devices correctly. CONCLUSION: We observed a significant increase in the BSI rate in two surgical units, SICU and OTU, associated with introduction of a needleless device. This increase occurred shortly after the needleless device was implemented and was associated with nurses' unfamiliarity with the device, and needless-device use and care practices different from the manufacturer's recommendations.

Catheterization, Central Venous↗

Adjuvant tamoxifen versus placebo in elderly women with node-positive breast cancer: long-term follow-up and causes of death.

PURPOSE: This study analyzes the long-term results and causes of death in elderly women with node-positive breast cancer who participated in a double-blind adjuvant trial that compared tamoxifen with placebo to determine the benefit of 2 years of treatment. PATIENTS AND METHODS: One hundred eighty-one women 65 to 84 years old were given 20 mg of tamoxifen or placebo daily for 2 years after stratification by estrogen receptor status, tumor size, and degree of lymph node involvement. Approximately 30% of patients were older than 70 years and 20% were older than 75 years. Eighty-five percent were estrogen receptor-positive. Median follow-up was 10 years. RESULTS: Among the 168 eligible patients, there have been 98 recurrences (59 placebo v 39 tamoxifen), with reduced distant and bone-only first sites in patients treated with tamoxifen. Median time to failure was 4.4 years for placebo versus 7.4 years for tamoxifen (log-rank P = .001). A similar number of new nonbreast cancers occurred in each arm (seven placebo v six tamoxifen), but a reduced number of opposite-breast cancers (five placebo v one tamoxifen) was noted. Overall, there were 102 deaths (57 placebo v 45 tamoxifen). Median survivals were 8.0 years with placebo and 8.5 years with tamoxifen (log-rank P = .063); 50% of the tamoxifen patients and 33% of the placebo patients are still alive. Sixty-one percent of the deaths were reported to have been caused by breast cancer recurrence, 4% by other cancers, and 22% by the sequelae of non-cancer-related illness, with equal distributions for cardiovascular and cerebrovascular disease. There was no increase in the number of endometrial or other types of cancer, or thrombotic or orthopedic complications in this older group. CONCLUSION: Tamoxifen currently is the treatment of choice for elderly women with breast cancer. It extends the time to treatment failure by 3 years and reduces the number of recurrences, deaths, distant and bone-only first recurrences, and second breast cancers.

Aged↗

[Pancreatic ductal carcinoma. Intra- and postoperative complications in palliative and curative interventions].

During 1982 and 1989 we treated 95 patients with ductal pancreatic carcinoma. Of these, 32.6% (31/95) had resection. The operation lethality was 3% (1/31), the clinical lethality 12% (4/31). The median length of survival was 6,8 months. Almost half of the potential curatively operated patients showed complications. Remarkable, that patients, operated in stages III and IV have been involved over proportionally often. Complications are the intra- and postoperative bleeding, the pancreatic fistulae, the intra-abdominal abscess, the sepsis and cardiopulmonary insufficiencies. 33 Patients underwent palliative operation, where the complication rate was significantly lower. Indeed, 5 patients who got a biliodigestive anastomosis, subsequently developed a pyloric or duodenal stenosis and had to be reoperated. The 30-day-lethality of the palliatively operated patients was 13% (4/33), the clinical lethality was 15% (5/33) and the median length of survival was 5,6 months. 24 patients underwent exploratory laparotomy and 7 patients were inoperable. Due to the higher complication rate in the curatively operated patients and only little higher life expectancy, an extensive surgical treatment of pancreatic carcinoma should only be considered effective in selected cases and in an early stage of carcinoma.

Adult↗

Cytochrome oxidase histochemistry in the rat hippocampus. A quantitative methodological study.

The diaminobenzidine (DAB) method was adapted for the microphotometric determination of cytochrome c oxidase (cyt ox) in the rat hippocampus. The qualitative and quantitative investigations at the light microscopic level showed that acetone and cytochrome c pretreatment of cryostat sections resulted in a significant increase of demonstrable cyt ox activities. The final incubation medium consisted of 7.5 mM DAB, 2% polyvinylalcohol (PVA) and 6% dimethyl sulfoxide in 0.1 M Hepes buffer; final pH 7.5. PVA was used to keep DAB and artificially oxidized DAB in solution. In the kinetic and endpoint measurements a linear response of the reaction with highest slope was observed only in the initial 5-6 min of reaction. Thereafter the slope decreased. Ultracytochemical demonstrations, which were performed as a topochemical control, showed reaction product only in mitochondria (cristae and intermembranous space). In contrast to vibratome sections all mitochondria reacted positively in cryostat sections of aldehyde-fixed hippocampi. The enhancement of reaction after acetone pretreatment of cryostat sections (light microscopic level) and after a freezing step in ultracytochemistry is discussed in connection with diffusion problems of DAB through mitochondrial membranes.

3,3'-Diaminobenzidine↗

Partial splenectomy for treatment of chronic idiopathic thrombocytopenia in childhood.

The aim of this paper was to demonstrate the efficiency of partial splenic resection in treatment of chronic idiopathic thrombocytepenie purpura (Werlhof-Disease). In all but one case remissions of thrombocyte counts over 100 Gpt/l could be achieved. Immunological studies demonstrate the existence of a suppressor-state after this operation, which could be responsible for success of this procedure. In contrast to general considerations the partial-splenectomized child must be considered as an immunological deficient organism for about 6 to 12 months. Restoration of immunological-means whole splenic functions-parameters is to expect always after this time.

Adolescent↗

Hemipelvectomy for neoplasms not originating in the pelvis.

10 patients underwent hemipelvectomy, mainly for sarcomas originating high in the thigh, or melanomas and epidermoid carcinomas metastatic to the groin. 1 patient died postoperatively, 3 lived 5-12 years and 1 died of unrelated cause 2 years after the operation, all free of recurrence. Tumors treated successfully were large and with indolent locoregional growth, often despite repeated unsuccessful local treatment attempts. These tumor characteristics should be considered as favorable features, in selecting such patients for hemipelvectomy. Conversely 3 patients with melanoma had short history before and died soon after the operation, contraindicating hemipelvectomy in locally advanced melanoma.

Adult↗

The prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancer. Findings from the NSABP clinical trials.

The present study examines the prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancer. Data were obtained from 1021 patients entered into two randomized prospective clinical trials of the NSABP. Tumor location proved to be a strong prognostic discriminant. Lesions located in the left colon demonstrated the most favorable prognosis. Tumors of the rectosigmoid and rectum had the worst prognosis with the relative risk of treatment failure for the latter being over three fold that of the left colon. When the relative risks associated with tumor location were adjusted for nodal imbalances, the left colon continued to demonstrate the most favorable prognosis. The presence of bowel obstruction also strongly influenced the prognostic outcome. Examination of the data without considering tumor location disclosed that patients with bowel obstruction were at greater risk for treatment failure than those without obstruction. The effect of bowel obstruction was influenced by the location of the tumor. The occurrence of bowel obstruction in the right colon was associated with a significantly diminished disease-free survival, whereas obstruction in the left colon demonstrated no such effect. This phenomenon was independent of nodal status and tumor encirclement, the latter two factors proving to be of prognostic significance independent of tumor obstruction. A multivariate analysis in which the covariate effects of sex, age, nodal status, tumor obstruction, encirclement, and tumor location were adjusted underscored the role of tumor location and obstruction as prognostic discriminants. The results indicate that the definition of prognostic factors can identify patient subsets with unique characteristics.

Carcinoma↗

Treatment of primary breast cancer with chemotherapy and tamoxifen.

We studied the possibility that the addition of tamoxifen to L-phenylalanine mustard combined with 5-fluorouracil enhances the benefit from the latter two drugs that has been observed in women with primary breast cancer and positive axillary nodes. Recurrence of disease was reduced at two years in patients given the three-drug regimen whose tumor estrogen-receptor levels were greater than or equal to 10 fmol. Among patients greater than or equal to 50 years old treatment failure was significantly reduced (P less than 0.001): by 51 per cent in those with one to three positive nodes and by 64 per cent in those with four or more. Higher receptor levels were associated with a greater probability of disease-free survival. Patients less than or equal to 49 years old were less responsive: those with one to three positive nodes received no benefit from tamoxifen at any receptor level, whereas those with four or more appeared to have reduced treatment failure associated with higher receptor levels. This adjuvant chemotherapy is not indicated in patients less than or equal to 49 years old whose tumor receptor levels are below 10 fmol; there is a suggestion of benefit in patients greater than or equal to 50 years old whose levels are low.

Age Factors↗