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Biomedical subjects

R Gärtner

Publications and source records attributed to R Gärtner.

At least 19 recordsLinked to original sources
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↗
PubMed1996

Influence of knowledge on iodine content in foodstuffs and prophylactic usage of iodized salt on urinary iodine excretion and thyroid volume of adults in southern Germany.

Thyroid volume, urinary iodine excretion as well as personal nutritional knowledge and individual iodine prophylaxis were determined during a health education program on iodine deficiency and prophylaxis in 1992. Participants were 472 male and 568 female (mean age 27.7 years) students and employees of five universities in the southern part of Germany. The study aimed to clarify the relationship between personal knowledge on iodine, individual iodine prophylaxis and parameters of iodine deficiency (thyroid volume, iodine excretion) in a well known iodine deficient area. Mean thyroid volume (mean +/- SD) was 19.7 +/- 8.3 ml in males and 15.8 +/- 7.1 ml in females. 25.5% of females and 19.9% of males showed thyroid volume above the upper normal values. Total mean urinary iodine excretion was 70.7 +/- 42 micrograms I/g creatinine reflecting WHO-grade-I iodine deficiency. 80.8% of total subjects used iodized salt and 43.2% stated to consume salt-water fish to meet their iodine requirement. The female non-users had significantly lower iodine excretion (no iodized salt, no salt-water fish: 61.4 +/- 31.3 vs. +iodized salt, +salt-water fish: 83.9 +/- 47.6 micrograms I/g creatinine; p < 0.05), however, thyroid volume was identical in these groups. The area of residence over the last 10 years did not significantly influence the thyroid volume. The goiter incidence increased with age. Although our study population was highly educated (81.8% students) and the subjects were provided with educational brochures immediately prior to the study, knowledge about iodine content of food was poor. We conclude that despite a high degree of voluntary iodine prophylaxis and educational programs the iodine intake is insufficient. The use of iodized salt in households, cafeterias, and also in food manufacturing must be increased for sufficient iodine prophylaxis.

Adult↗
PubMed1996

Role of basic fibroblast growth factor in the pathogenesis of nodular goiter.

Thyroid epithelial cells are known to produce several growth factors and cytokines which influence thyroid cell growth and function in an autocrine and/or paracrine manner. It is already known that insulin-like growth factor I (IGF I) is overexpressed in toxic adenomas whereas epidermal growth factor (EGF) is found predominantly in thyroid neoplasia. We now investigated the expression of bFGF by immunohistochemistry in thyroid tissue of patients with toxic adenoma (n = 27), cold nodules (n = 27) and for comparison in Graves' disease (n = 5). In addition bcl-2-oncoprotein expression in these tissues were also detected by immunohistochemistry. Most of bFGF immunostaining was found in the connective tissue of all thyroid tissues with a predominance in adenomas and in Graves' diseases. The collagen surrounding the thyroid follicles close to their basal membrane were homogeneously and intensively stained. All the cytoplasm of fibroblast in the connective tissue were strongly positive. Within the cytoplasm of only 2-10% thyroid epithelial cells bFGF immunostaining was found without any difference between toxic adenomas or cold nodules. In the tissue of patients with Graves' disease, less than 2% of thyrocytes were stained. All thyroid epithelial cell showed clearly an immunostaining for bcl-2-oncoprotein in nodular goiter as well as Graves' disease.

Adenoma↗
PubMed1996

Stimulation of thyroid cell proliferation by epidermal growth factor is different from cell growth induced by thyrotropin or insulin-like growth factor I.

Isolated intact porcine thyroid follicles free of contaminating single cells were embedded in "Matrigel", which is a gel-forming basement membrane preparation containing mainly collagen type IV, laminin, heparan sulfate proteoglycans and entactin. Follicles were treated with different growth factors: thyrotropin (TSH), insulin-like growth factor I (IGF-I), epidermal growth factor (EGF) or transforming growth factor beta. Cell proliferation was quantified by counting cell numbers. Morphological studies were done by photodocumentation and analysis of histology by light and electron microscopy. The thyrocytes had the physiological polarity with follicular cell arrangement, microvilli at the apical membrane, desmosomes and tight junctions. The lumen contained colloid. Iodide organification (10.2 +/- 2.1 vs 26.1 +/- 5.8 pmol/10(6) cells; TSH 0.1 mU/ml) and release of thyroid hormones (thyroxine, 1754 +/- 207 vs 2890 +/- 460 pg/10(6) cells; triiodothyronine, 164 +/- 22 vs 412 +/- 106 pg/10(6) cells; TSH, 1mU/ml) were significantly stimulated by TSH. There was no basal growth rate in serum-free medium but proliferation was slightly stimulated with TSH (1 mU/ml; 149 +/- 19%) and in the same order of magnitude with IGF-I (10 ng/ml; 159 +/- 23%) but without follicle neoformation. In contrast, BGF (1.0-5.0 ng/ml) induced thyrocyte proliferation dose dependently three- to sixfold. With BGF up to 2 ng/ml, buds of new follicles formed surrounding pre-existing follicles. With BGF higher than 3 ng/ml, typical papillary structures developed. Transforming growth factor beta inhibited this dedifferentiated growth. A migration of single cells into the gel was never observed. Thus, three-dimensional culture of isolated thyroid follicles in "Matrigel" provides a tool for investigating the regulation of follicular growth and neoformation close to the in vivo situation.

Animals↗
PubMed1996

Evidence that iodolactones are the mediators of growth inhibition by iodine on the thyroid.

Different iodolipids have been identified within the last decades in thyroid cells exposed to iodine in vitro as well as in vivo. Iodolipids have been supposed to be involved in thyroid autoregulation, but no specific compounds could be found. A new approach was stimulated by the finding that rat thyroid lobes were able to iodinate arachidonic acid and docosahexaenoic acids in vitro. Meanwhile 6-iodo-5 hydroxy-eicosatrienoic acid (delta-iodolactone) has been identified in human thyroid tissue, but only after treating the patients with high doses of iodine before thyroidectomy, whereas in untreated endemic goiter this delta-iodolactone could not be found. In rats treated with iodolactones, methimazole induced goiter formation could be prevented. In human and porcine thyroid cells in vitro, delta-iodolactone inhibited epidermal growth factor (EGF) induced proliferation in 50-fold lower concentrations than iodide itself. Furthermore it could be demonstrated that only the IP3-, but not the cAMP generation in porcine thyroid cells could be inhibited by this compound. Also a structure specifity for delta-iodolactones for the biological activity could be shown. We will summarize and discuss these important new findings on the role of iodolactones on thyroid growth.

Animals↗
PubMed1996

[CASUS model trial. A computer-assisted author system for problem-oriented learning in medicine].

The CASUS-project, a three year publicly funded effort to improve the quality of continuing medical education in Germany, has one major goal: The development and evaluation of an easy-to-handle author-system for problem-oriented learning in medicine. On the theoretical basis of the cognitive apprenticeship-approach, the concept of a teaching and learning database as a hypermedia system was built. The student should learn to manage authentical problems in the form of authentical clinical cases. The step-by-step learning process is expert-guided by the clinical authors of each case. The creation of various differential diagnoses by the learner is strongly supported in the process. The structure of the program can also be used for case-based examinations. In parallel to the technical development, a case-selection process for medical students students in internal medicine was initiated. About 120 relevant diseases were identified to be represented in the CASUS-case library. Prevalence, transferability of knowledge, treatability, urgence of treatment and preventive aspects were used as selection criteria. The system will be evaluated during the implementation of test cases and will then be available to be used by authors and students on a routine basis in 1997.

Authorship↗
PubMed1995

Insulin-like growth factor I messenger ribonucleic acid expression in porcine thyroid follicles is regulated by thyrotropin and iodine.

Insulin-like growth factor I (IGF-I) has been shown to be released from thyrocytes in vitro. We investigated IGF-I mRNA expression during treatment with thyrotropin (TSH), forskolin and potassium iodide (KI) in intact porcine thyroid follicles ex vivo. Porcine thyroid follicles were prepared by collagenase digestion and cultured in the presence of TSH, forskolin or KI. After different incubation times, mRNA was isolated and examined by Northern hybridization with a porcine IGF-I cDNA probe of 405 bp in length. In untreated follicles no IGF-I mRNA was found, whereas in follicles stimulated with TSH an IGF-I mRNA of 7.0 kb was detected after 24 h, which persisted for another 24 h. Forskolin treatment mimicked the TSH effect, indicating that IGF-I mRNA expression may be stimulated by the adenylate cyclase pathway. Preincubation of the porcine follicles with KI decreased dose dependently the TSH-induced IGF-I mRNA expression, with complete inhibition at 10 mumol/l KI. These results suggest that TSH acts via the cAMP pathway to enhance IGF-I mRNA expression, which then may lead to an autocrine IGF-I stimulation. The IGF-I mRNA expression is under negative control of iodide.

Adenylyl Cyclases↗