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Biomedical subjects

R Gärtner

Publications and source records attributed to R Gärtner.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Significance of selenium in intensive care medicine. Clinical studies of patients with SIRS/sepsis syndrome].

Selenium is an essential component of the intracellular antioxidant system as a structural component of the active center of the glutathione peroxidase enzymes. These selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and selenium seems to play a direct role in the regulation of inflammatory processes. In conditions of systemic inflammatory response or sepsis, patients are exposed to severe oxidative stress. These patients already have both, a decreased plasma selenium and glutathione peroxidase activity at admission to the ICU as has been shown in several studies. The degree of selenium deficiency is correlated with the severity of disease and the incidence of mortality. The reason for the low plasma selenium levels is unknown. Especially it would be of interest a) if the low plasma selenium is the consequence of the systemic inflammatory response with distribution of selenium in other compartments of the body, b) most important, whether the substitution of selenium might improve the outcome and decrease the mortality rate of these patients. In 2 independently performed intention-to-treat studies including patients with systemic inflammatory response syndrome or sepsis a beneficial effect of selenium supplementation on multiple organ function and outcome could already be demonstrated as well as a tendency of an improved mortality rate. A prospective analytical study clearly could demonstrate the inverse relationship between low plasma selenium and morbidity and mortality of patients with SIRS/sepsis. The results of these studies are so convincing, that we propose a randomized, prospective, double blind multicenter phase-III study including patients with systemic inflammatory response syndrome or sepsis to investigate, whether a high-dose selenium substitution in addition to the recommended treatment strategies for patients with sepsis improves outcome and mortality rate of these patients.

APACHE↗
PubMed1999

Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

BACKGROUND: Accelerated bone loss is a well-recognized complication after cardiac transplantation (HTx) due to immunosuppressive therapy. The purpose of this prospective, longitudinal, randomized, placebo-controlled, double-blind study was to investigate the effect of calcitriol (1,25-dihydroxyvitamin D3) in the prevention of bone loss and fracture rate after HTx. METHODS: Basic therapy included 1000 mg of calcium daily and sex hormone replacement in hypogonadal patients. A total of 132 patients (111 male, 21 female; mean age: 51+/-10 years; 35+/-25 months after HTx) were randomized to 0.25 microg of calcitriol or placebo. Bone mineral density (BMD, g/cm2; T score, %) of the lumbar spine and x-rays for the assessment of vertebral fractures were performed at baseline and after 12, 24, and 36 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall BMD was significantly decreased after HTx (T score 87+/-13%). BMD increased continuously within the study period in the calcitriol group (1 year: 2.2+/-4.8%; 2 years: 3.9+/-5.4%; 3 years: 5.7+/-4.4%) as well as in the placebo group (1 year: 1.8+/-4.9%; 2 years: 3.7+/-6.5%; 3 years: 6.1+/-7.8%) without statistical difference between the groups. Fracture incidence was low during the study interval (1 year: 2.0%; 2 years: 3.4%; 3 years: 0%). Hypogonadism (20%) was associated with a lower BMD (78+/-12% vs. 88+/-12%; P<0.01) and a higher increase (35%) after hormone replacement in comparison to normogonadal patients. Increased intact parathyroid hormone and bone resorption markers decreased significantly during therapy. CONCLUSIONS: Calcium supplementation and sex hormone replacement in hypogonadism proved a sufficient long-term prevention therapy to improve decreased BMD and to prevent fractures after HTx. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role in the long-term bone loss and should therefore be monitored and treated adequately. Low-dose calcitriol demonstrated no significant extra benefit regarding BMD and fracture rate in the long-term period after HTx.

Adult↗
PubMed1999

Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture.

The inflammatory-mechanistic basis of subacute thyroiditis remains unclear. To elucidate the roles of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) in the inflammatory process, their immunoexpression was examined in biopsy specimens of ten cases. At the granulomatous stage, all cases expressed VEGF, bFGF, PDGF, and TGF-beta1 in monocytes/macrophages infiltrating into follicle lumina, and in both epithelioid histiocytes and multinucleated giant cells of the granulomas. In fibroblasts and endothelial cells around the granulomas, all cases displayed VEGF, bFGF, and PDGF, but TGF-beta1 was detected only in fibroblasts in two cases. No cases expressed EGF in any of the above cell types. At the regenerative stage, all cases expressed VEGF, bFGF, and EGF in regenerating thyrocytes, whereas three and no cases displayed PDGF and TGF-beta1, respectively. Ten, seven and six cases expressed PDGF in fibroblasts, endothelial cells, and monocytes, respectively. In these cell types, all cases expressed VEGF and bFGF, whereas no cases displayed TGF-beta1 and EGF. To estimate the roles of these growth factors in thyroid tissue regeneration, their effects on thyroid folliculogenesis and angiogenesis were examined using collagen gel culture of thyrocytes and endothelial cells, respectively. Cell proliferation was also studied by bromodeoxyuridine (BrdU) uptake. EGF decreased follicle formation and TGF-beta1 drastically inhibited it, but the others had no effect. VEGF showed the greatest effect on vessel formation, although all of the others promoted it. EGF and VEGF or bFGF caused the highest BrdU uptake in thyrocytes and endothelial cells, respectively. The data suggest firstly, that at the granulomatous stage of subacute thyroiditis, growth factor-rich monocytes/macrophages infiltrating into follicle lumina trigger the granulomatous reaction, and VEGF, bFGF, PDGF, and TGF-beta1 produced by the stromal cell types tested mediate the reaction; secondly, that at the regenerative stage, EGF serves follicle regeneration through its mitogenic effect on thyrocytes, although some cofactors with EGF are involved in folliculogenesis and the decreased expression of TGF-beta1, a fibrogenic factor, contributes to thyroid tissue repair; and thirdly, that VEGF and bFGF are more responsible for the angiogenesis at both stages than the other factors studied.

Cell Culture Techniques↗
PubMed1999

Drug resistance in intensive care units.

Intensive care units (ICUs) are generally considered epicenters of antibiotic resistance and the principal sources of outbreaks of multi-resistant bacteria. The most important risk factors are obvious, such as excessive consumption of antibiotics exerting selective pressure on bacteria, the frequent use of invasive devices and relative density of a susceptible patient population with severe underlying diseases. Infections due to antibiotic-resistant bacteria have a major impact on morbidity and health-care costs. Increased mortality is not uniformly shown for all of these organisms: Methicillin-resistant Staphylococcus aureus (MRSA) seems to cause significantly higher mortality, in contrast to vancomycin-resistant enterococci (VRE). Therefore it is essential to diminish these potential risk factors, especially by providing locally adapted guidelines for the prudent use of antibiotic therapy. A quality control of antimicrobial therapy within a hospital, and especially within the ICU, might help to minimize the selection of multidrug-resistant bacteria. The restricted use of antimicrobial agents in prophylaxis and therapy has also been shown to have at least temporal effects on local resistance patterns. New approaches to the problem of drug resistance in ICUs are badly needed.

Anti-Bacterial Agents↗
PubMed1999

Induction of apoptosis in porcine thyroid follicles by transforming growth factor beta1 and epidermal growth factor.

For thyroid cells in culture DNA fragmentation and morphological changes related to apoptosis were first described in dog thyroid cells after deprivation of serum, epidermal growth factor or thyrotropin. With intact porcine thyroid follicles in three-dimensional culture, the effect of deprivation of growth factors and of incubation with transforming growth factor beta1 (TGF-beta1), epidermal growth factor (EGF), thyrotropin (TSH) or insulin-like growth factor I (IGF-I) on the incidence of apoptosis was studied. Thyroid follicles were embedded in growth factor-depleted Matrigel and cultured in serum-free medium with or without growth factors for 7 days followed by incubation for 4, 24 and 72 h with TGF-beta1 (2 or 5 ng/mL). The percentage of apoptotic cells was determined by direct counting in electron-microscopy. Approximately 1% of apoptotic bodies could be detected in unstimulated follicles. This was unchanged in the presence of TSH (1 mU/mL) or IGF (10 ng/mL) but significantly increased up to 3.99 +/- 1.24% with 2 ng/mL of EGF. After incubation with TGF-beta apoptosis increased dose-dependently to 4.05 +/- 0.67% with 2 ng/mL TGF-beta1 and 5.16 +/- 1.75% with 5 ng/mL TGF-beta1. The incidence of necrotic cells remained constant at about 1 to 2%. Preincubation of follicles with 2 ng/mL of EGF followed by incubation with 5 ng/mL TGF-beta1 increased the rate of apoptic bodies up to 13.19 +/- 1.9%. We conclude that growth factor depletion in thyroid follicles in three-dimensional culture does not lead to apoptosis. TGF-beta1, however, induces apoptosis even in quiescent thyroid follicular cells and is significantly more pronounced in growing thyroid cells. EGF, which is a dedifferentiating growth factor for thyroid cells, also induces apoptosis. As EGF enhances TGF-beta1 mRNA and protein in thyroid follicular cells, the induction of apoptosis by EGF might also be due to TGF-beta1.

Animals↗
PubMed1999

Presence of a soluble inhibitor of thyroid iodination in primary cultures of thyroid cells.

Monolayer cultures of thyroid cells lose their iodide organification capacity a few days before the disappearance of thyroid peroxidase (TPO) activity. The present studies were performed in order to clarify this point. The above mentioned difference was due to the presence of an inhibitor in the monolayer thyroid cells culture, given that total homogenate prepared from confluent cells caused a significant inhibition of activity of TPO from fresh tissue. The inhibitor was localized in the 105000g supernatant of the homogenate of the cell culture, but not in a similar preparation obtained from fresh thyroid. It is thermostable, dialyzable and has a molecular weight of less than 2 kDa. Addition of the inhibitor at the end of the reaction of tyrosine iodination failed to alter the results. This fact suggests that the compound does not destroy the iodinated product. The presence of the cytosolic inhibitor was observed in monolayer thyroid cell cultures of different species (bovine, porcine, rat and human) but not in free follicles cultures.

Animals↗
PubMed1998

Skeletal effects of low-dose cyclosporin A in aged male rats: lack of relationship to serum testosterone levels.

The aim of this study was to investigate the skeletal effects of cyclosporin A (CsA) in a dose range relevant to clinical medicine in lumbar vertebral cancellous bone of aged male rats and to correlate these effects with possible changes in serum testosterone levels. Thirty-one 18-month-old male Wistar rats were divided into four weight-matched groups and subcutaneously injected with either 0, 1, 3, or 5 mg of CsA/kg of body weight three times per week After 4 weeks of treatment, all rats were killed after in vivo fluorochrome labeling and the first lumbar vertebrae analyzed by quantitative histomorphometry. Serum was analyzed for total calcium, creatinine, alkaline phosphatase, osteocalcin, parathyroid hormone, total testosterone, and CsA levels. CsA administration resulted in a dose-dependent increase in serum osteocalcin levels and in histomorphometric indices of cancellous bone turnover in the axial skeleton. Furthermore, CsA-treated rats showed a deterioration of vertebral cancellous bone structure with increased discontinuity of the trabecular bone network due to trabecular plate perforations. Serum testosterone levels were not significantly changed by CsA treatment and were uncorrelated to all biochemical or histomorphometric indices of bone turnover. We conclude that the 4-week administration of CsA at doses that are close to those used in transplantation patients induced high turnover osteopenia in the axial skeleton of aged, 18-month-old male rats, and that these effects were likely not mediated by changes in serum testosterone levels.

Aging↗
PubMed1997

[Selenium administration in sepsis patients].

BACKGROUND: It has been hypothesized that low serum selenium concentrations, associated with low glutathione peroxidase activities in critical ill patients may contribute to decreased cleavage from free radicals and deteriorate the clinical outcome. PATIENTS AND METHODS: We therefore performed a controlled, prospective study including 42 patients with inflammatory response syndrome and an APACHE-II score > or = 15. Whereas the controls (Se-, n = 21) received 35 micrograms sodium selenite during the whole treatment period the selenium substitution group (Se+, n = 21) received additional 500 micrograms, 250 micrograms and 125 micrograms sodium selenite, each amount for 3 days. Clinical outcome was monitored by APACHE-III score, documentation of acute renal failure, respiratory insufficiency and the mortality rate until discharge from the hospital. RESULTS: The mean APACHE-II(III) score on admission was 20.6 (68.3) in the Se- versus 20.1 (61.0) in the Se+ group. Age, sex, underlying diseases, the serum selenium levels and glutathione peroxidase activities on admission were equally distributed in both groups. Selenium substitution was followed by a significant increase in serum selenium levels and glutathione peroxidase activity to normal levels, whereas in controls both parameters remained low. The APACHE-III score significantly improved on day 7 (p = 0.018) and 14 (p = 0.041) in the Se+ group. Hemodialysis because of acute renal failure was necessary in 9 (Se-) versus 3 (Se +) patients (p < 0.04). Overall mortality rate in the Se+ group was 33.5% versus 55% in the Se- group (p = 0.13). A subanalysis of those patients with an APACHE-II score > 20 (n = 10) in each group revealed a significant reduction in mortality from 70% to 30% (p = 0.013). No negative side effects of selenium were seen. CONCLUSION: Selenium substitution significantly improves clinical outcome and reduces the incidence of acute renal failure.

APACHE↗
PubMed1997

[Immunogenic hyperthyroidism with hyperdynamic heart failure and early cirrhotic transformation of the liver].

HISTORY AND CLINICAL FINDINGS: A 58-year-old woman was admitted because of jaundice, ascites and marked oedema. For three years she had suffered from nervousness, decreasing fitness and weight loss, which had been assumed as due to chronic alcoholism. Liver biopsy revealed extensive fibrosis, in part with early cirrhotic transformation. This was followed by cardiac failure with atrial fibrillation (ventricular rate 140/min) and marked pleural effusions. The thyroid was diffusely enlarged and there were signs of exophthalmos. INVESTIGATIONS: Bilirubin concentration was 3 mg/dl, lactate dehydrogenase activity was 310 U/l, cholesterase 1.3 kU/l and the prothrombin test was 21%. The TSH level was 0.01 microU/ml while the free thyroxine level was 4.7 ng/dl and that of free triiodothyronine 13.5 pg/ml. Chest radiograph revealed cardiomegaly, bilateral peripheral pulmonary congestion and pleural effusions to midfield. Right heart catheterization excluded pulmonary hypertension; cardiac output was 10l/min. The thyroid was enlarged on ultrasound and diffusely echopoor, as in immune thyroid disease. TREATMENT AND COURSE: Cardiac failure regressed and thyroid function normalized within ten days on propranolol, 4 x 40 mg and thiamazole 3 x 40 mg daily intravenously. Subtotal thyroidectomy was performed three weeks later with subsequent thyroid hormone substitution. Liver functions were normal six months later and ultrasound showed no signs of cirrhotic change and the ascites had resolved. CONCLUSION: Hyperthyroidism is frequently associated with changes in liver functions. In extreme cases, high-output cardiac failure may occur, with liver congestion and clinical as well as histological changes like those in liver cirrhosis.

Adrenergic beta-Antagonists↗
PubMed1997

Cyclic plasma IL-6 levels during normal menstrual cycle.

Steroid hormones including sex hormones are known to influence cytokine production by cells in vitro. We investigated whether there are differences in cytokine production in vivo and ex vivo during the menstrual cycle in five ovulating women compared with five pregnant women and nine males. Interleukin 6 (IL-6) in plasma changed periodically during 12 of 13 cycles in five women. The IL-6 levels were lowest in the luteal phase when progesterone levels were elevated and highest preovulatory when progesterone levels were low (P < 0.009). This phenomenon was unrelated to changes in haematocrit or albumin and independent of cortisone, growth hormone, luteinizing or follicle stimulating hormone and testosterone. In contrast to IL-6, the soluble IL-6 receptor did not vary significantly during the menstrual cycle. In comparison, nine males and five pregnant women had low plasma IL-6 levels comparable with women during the luteal phase. In addition, levels of IL-6, IL-10 and TNF were determined after whole blood stimulation with lipopolysaccharide ex vivo during a menstrual cycle. Neither the number of CD-14++ or CD14/CD16+ cells nor the amounts of IL-6, IL-10 and TNF after stimulation showed cyclic changes. We suggest that sex hormones, especially oestrogen and progesterone, may influence immune responses by decreasing basal IL-6 levels in vivo.

Female↗
PubMed1997

Comparison of urinary iodine excretion and thyroid volume in students with or without constant iodized salt intake.

We compared the iodine excretion and thyroid volumes in young students with or without continuous use of iodized salt in household. Students from five different Universities in Bavaria were evaluated on a voluntary basis. Exclusion criteria were age above 35 years, known thyroid illness except simple goiter, application of x-ray contrast medium within the last 6 months or other known exposure to high doses of iodine. The participants answered a questionnaire indicating permanent utilization of iodized salt for more than one year during all their meals, the intake of iodide tablets and eating in student cafeterias, offering meals that are prepared with iodized salt. Morning spot urine was drawn from each participant to measure creatinine correlated iodide excretion and thyroid volume was measured by ultrasound. In this study, 932 students could be included, mean age was 24 years, 501 females, 431 males. Chronic users of iodized salt were 75.9% (80.4% females, 70.5% males), 1.7% were on iodide tablets (200 micrograms/day) and 2.6% were on TSH suppressive therapy with thyroid hormones. The mean iodide excretion in chronic iodized salt users was 72.0 (+/- 68.7) micrograms/g creatinine compared to non-users 66.0 (+/- 65.4) micrograms/g creatinine (p < 0.003). Those students who were on iodide tablets had a mean iodide excretion of 130.0 +/- 72.0 micrograms/g creatinine. Mean thyroid volume was 14.1 (4.4-44.1) ml in females and 17.1 (6.6-64.4) ml in males, solid thyroid nodules were detected in 5.9% and thyroid cysts in 2.7% of the participants without any difference between iodized salt users or non-users.

Adolescent↗
PubMed1997

Functioning thoracic paraganglioma: association with Von Hippel-Lindau syndrome.

Functioning thoracic paraganglioma (pheochromocytoma) is unusual and therefore suggestive of a pathogenesis distinct from that of sporadic adrenal pheochromocytoma. To determine whether the pheochromocytoma-associated syndromes Von Hippel-Lindau disease (VHL) and multiple endocrine neoplasia type 2 (MEN 2) play a role in the development of thoracic functioning paragangliomas, germline DNA from five unselected patients with this rare tumor was analyzed for mutations in the genes that predispose to VHL and MEN 2. Genetic investigations and further clinical data revealed that three had VHL, with two different germline mutations of the vhl gene, but no individual was affected by MEN 2. Two of the three patients with VHL did not show any additional VHL-associated lesions. This result suggests that VHL should be considered in the differential diagnosis of thoracic pheochromocytoma, as such a diagnosis carries further important implications for the patient and family. Conversely, in patients suspected of a catecholamine-secreting tumor and known VHL, thoracic localization should be considered if an adrenal pheochromocytoma cannot be detected.

Adolescent↗