Biomedical subjects

M Slawik

Publications and source records attributed to M Slawik.

9 recordsLinked to original sources

PubMed2006

[Obesity 2006].

Despite the fact that the last decade has seen major advances in our knowledge of obesity, the average unsatisfactory successes of lifestyle changes and pharmacological treatment strategies clearly show how very far obesity research and treatment still has to go. What is most regrettable, however, is the fact that, in contrast to the WHO, the German Social Security Code V does not recognize obesity as a disease. This means ignoring the approaching flood of costs associated with obesity, which will put a great strain our health system.

Adolescent↗

PubMed2006

[Genetics and pathophysiology of obesity].

Obesity is one of the major health problems in developed countries. More than 35% of adults in Germany are considered to be overweight (BMI 25-29.9 kg/m(2)) and approximately 15-20% to be obese (BMI >30 kg/m(2)). Overweight and obesity result from chronic disruption of energy balance. Recent progress in understanding of appetite control and energy expenditure has elucidated a complex integrated system of energy homoeostasis. Although changes in nutritional habits and reduction of physical activity are the main characteristics leading to the strong increase in obesity, it is now recognized that obesity is not only caused by a lack of will power, but can be a consequence of metabolic defects. As obesity results from a genetic make-up favoring weight gain in an "obesigenic" environment the elucidation of the underlying molecular mechanisms might be translated in novel therapeutic options in the future.

Appetite Regulation↗

PubMed2006

Treatment with insulin glargine does not suppress serum IGF-1.

AIMS: A 6-8-fold higher insulin-like growth factor 1 (IGF-1) receptor binding affinity in vitro is reported for the insulin analogue glargine compared with human insulin. This study evaluates the in vivo significance by exploring the growth hormone (GH)-IGF-1 axis. Assuming a higher binding affinity of insulin glargine to pituitary IGF-1 receptors, serum IGF-1 concentrations should decrease via negative feedback. METHODS: In a crossover study, insulin glargine or NPH insulin, respectively, were used in identical doses as basal insulins in treatment periods of 3 weeks. RESULTS: Overall glycaemic control was not different between the treatment regimens. In contrast to the hypothesis, serum IGF-1 concentrations were higher during insulin glargine treatment compared with NPH insulin in patients with Type 1 diabetes (177 +/- 18 vs. 159 +/- 18 microg/l, P < 0.02, n = 17, age 28 +/- 2 years). The effect on IGF-1 was most pronounced in male patients with Type 1 diabetes (174 +/- 11 vs. 146 +/- 10 microg/l, P < 0.02, n = 10), but was not significant in patients with Type 2 diabetes (92 +/- 9 vs. 86 +/- 8 microg/l, NS, n = 25, age 66 +/- 2 years). CONCLUSIONS: In contrast to our hypothesis, serum IGF-1 did not decrease, but rose during insulin glargine treatment, suggesting an absence of relevant IGF-1-like activity of glargine at the level of the pituitary. Improved plasma glucose at dawn during glargine treatment may intensify growth hormone surges and increase IGF-1 synthesis. Significant increases were seen in younger patients, compatible with the higher activity of the GH-IGF-1 axis in this age group.

Adult↗

PubMed2006

PET with 18F-DOPA in the imaging of parathyroid adenoma in patients with primary hyperparathyroidism. A pilot study.

UNLABELLED: Preoperative localization of parathyroid adenomas (PA) can shorten operation time and improve curative rate; it becomes especially important in minimally invasive surgical techniques. AIM of this study was to investigate whether positron emission tomography (PET) with 3-,4-dihydroxy-6- (18) F-fluorophenylalanine ( (18) F-DOPA), which showed very promising results in other neuroendocrine tumours, also helps to localize PA. PATIENTS, METHODS: Eight patients with proven primary hyperparathyroidism were studied preoperatively with PET. Seven also underwent scintigraphy with (99m) Tc-MIBI and ultrasonography of the neck. All patients were operated and the histological finding was used as a gold standard. RESULTS: All eight patients had a histologically proven PA. None of the PA showed any detectable uptake of (18) F-DOPA. However, ultrasonography detected 5/7 PA, scintigraphy detected 3/7 PA. CONCLUSION: These results suggest that PET with (18) F-DOPA is not useful in the detection of PA in patients with primary hyperparathyroidism.

Adenoma↗

PubMed2005

Low-dose glucose infusion after achieving critical hypoglycemia during insulin tolerance testing: effects on time of hypoglycemia, neuroendocrine stress response and patient's discomfort in a pilot study.

OBJECTIVE: The insulin tolerance test (ITT) is regarded as the gold standard for the evaluation of pituitary ACTH and growth hormone reserve. However, the intended critical hypoglycemia results in considerable discomfort and requires close surveillance during the test. DESIGN AND METHODS: In a pilot study, we evaluated whether the ITT could be markedly simplified, made less hazardous and more convenient by routine i.v. low-dose glucose administration after hypoglycemia has been achieved. Sixteen healthy subjects (three females, 13 males) were tested twice in a randomized, single-blinded fashion, receiving 0.15 IU insulin/kg body weight as an i.v. bolus. After hypoglycemia (serum glucose less than 2.2 mmol/l) had been achieved, 500 ml isotonic saline (protocol A (A)), or 500 ml 5% glucose solution (protocol B (B)) were infused over 30 min. RESULTS: Compared with saline, glucose infusion shortened the period of hypoglycemia from 31 + 14 to 17 + 6 min (P < 0.01). In addition, prolonged duration of hypoglycemia (>45 min) was reduced (6 subjects in protocol A vs none in protocol B). Despite shorter duration of hypoglycemia, all subjects had adequate stimulated cortisol (>500 nmol/l) and hGH (>5 microg/l) levels. Mean peak concentrations of plasma ACTH (24 +/- 12 pmol/l (A) vs 21 +/- 8 pmol/l (B)), serum cortisol (690 +/- 83 nmol/l vs 634 +/- 83 nmol/l) and serum hGH (26 +/- 16 microg/l vs 22 +/- 13 microg/l) were slightly, but not significantly lower. In contrast, glucose infusion significantly reduced peak plasma epinephrine levels at 45 min (4.96 +/- 4.91 pmol/l (A) vs 1.53 +/- 1.1 pmol/l (B), P < 0.05) and ameliorated discomfort, as evaluated by a visual analog scale (P < 0.05). CONCLUSIONS: Taken together, our pilot study suggests that, while the duration of hypoglycemia is shortened and acute epinephrine response is reduced, low-dose infusion of glucose does not significantly alter peak cortisol and growth hormone responses during ITT. Studies with a larger number of subjects and patients with suspected hypopituitarism are needed to further evaluate this modified protocol.

Adrenocorticotropic Hormone↗

PubMed2003

Is the plasma ACTH concentration a reliable parameter in the insulin tolerance test?

OBJECTIVE: The insulin tolerance test (ITT) is an established standardized test for the evaluation of the hypothalamic-pituitary-adrenal axis. While a peak cortisol value of >18 microg/dl is usually interpreted as a sufficient response to the ITT, the plasma ACTH response has not yet been standardized. METHODS: We evaluated retrospectively the peak plasma ACTH concentrations during 140 ITTs in 125 patients with suspected pituitary insufficiency and prospectively in 15 healthy subjects. RESULTS: All healthy subjects had a peak cortisol concentration >/=18 microg/dl; 32 of 125 tests in the patients showed an insufficient cortisol response (peak cortisol concentration <18 microg/dl). The peak stimulated ACTH concentration in patients with secondary adrenal insufficiency (SAI) was 49.2+/-37.2 pg/ml (mean+/-s.d.) vs 130.9+/-89.3 pg/ml in patients without SAI, and 110.9+/-55.4 pg/ml in normal subjects (P<0.001). There was a weak, but significantly positive correlation between the peak ACTH and peak cortisol concentrations (rho=0.446, P<0.001), but there was also a very wide spread of the values. Defining a cut-off value for the peak plasma ACTH concentration with a sufficient sensitivity and specificity to identify patients with an impaired hypothalamic-pituitary-adrenal (HPA) axis was not possible. A peak plasma ACTH <20 pg/ml as a cut-off value had a sensitivity of 25% and a specificity of 98% for SAI. A cut-off value of a peak plasma ACTH <140 pg/ml had a sensitivity of 97% but a low specificity of 39%. CONCLUSIONS: Although there is a significant positive correlation between the peak ACTH and the peak cortisol concentrations, we conclude that there is no additional benefit in determining the ACTH concentrations during an ITT. Because of the strong variations of the values, the peak ACTH concentration is a poor parameter for the evaluation of the HPA axis.

Adrenal Insufficiency↗

PubMed2000

Deoxycholic acid (DOC) affects the transport properties of distal colon.

Secondary bile acids can induce diarrhea. In the present study we examined the effects of deoxycholic acid (DOC) on equivalent short-circuit current (Isc) in rabbit colon and the cellular mechanisms involved in DOC action (rabbit and rat). Luminal DOC inhibited amiloride-sensitive Na+ absorption. In the presence of amiloride luminal DOC had a concentration dependent effect on Isc. Low concentrations (1-10 micromol/l) induced a lumen-positive current (51+/-3 microA/cm2, 10 micromol/l, n=7) which was inhibited by luminal Ba2+ suggesting the activation of a luminal K+ conductance. Higher luminal concentrations induced a lumen-negative current (-76+/-9 microA/cm2, 100 micromol/l, n=11). Basolateral application of DOC, also in the presence of amiloride, only induced lumen-negative Isc, (-58+/-10 microA/cm2, 100 micromol/l, n=6, EC50= 3 micromol/l). This current could be abolished completely by the K+ channel blocker 293B, a selective inhibitor of cAMP-dependent Cl- secretion. This action of DOC on Isc was additive to the effect of carbachol (CCH) but not additive to that of cAMP. In intact rat colon mucosa pre-treated with DOC a significant increase in cAMP production was observed. Fura-2 measurements of cytosolic Ca2+ activity ([Ca2+]i) in isolated colonic crypts (rabbit and rat) showed that 100 micromol/l DOC induced a weak [Ca2+]i increase. Whole-cell measurements of membrane voltage in isolated rat colonic crypts revealed a hyperpolarization by DOC (4.9+/-0.8 mV, 100 micromol/l, n=8) but a depolarization by prostaglandin E2 (PGE2, via cAMP) (24+/-7 mV, n=8). The present data show that DOC acts at more than one target in the colon: in the intact mucosa it activates luminal K+ channels and Cl- secretion and this is paralleled by an increase in cAMP production. In isolated crypts DOC probably activates a Ca(2+)-regulated K+ conductance but has no effect on cAMP. Hence DOC probably activates ion channels or channel-regulating factors in colonocytes and acts on non-epithelial cells to activate Cl- secretion indirectly.

Amiloride↗

PubMed2000

Molecular adrenocortical tumourigenesis.

Adrenocortical neoplasms are the most frequent abnormality of the adrenal cortex. Most of these lesions are clinically silent and are detected incidentally by ultrasound or computed tomography. The prevalence of these so-called 'incidentalomas' in the general population is around 1%, increasing with age and reaching 6% among those in the age range 60-70 years. In contrast, primary adrenocortical carcinoma, a highly malignant tumour, is rare, having an incidence of one case per million per year. Recent progress has been achieved in the understanding of adrenocortical tumourigenesis by mapping and identification of genes responsible for hereditary tumours that involve the adrenal gland. Investigation of the clonal composition of adrenal tumours demonstrates that adrenal carcinomas are monoclonal, whereas adrenal adenoma may be polyclonal in approximately 25-40% of cases. Oncogenes and tumour-suppressor genes involved in adrenal carcinomas include mutations in the p53 tumour-suppressor gene and rearrangements of the chromosomal locus 11p15.5 associated with IGF II hyperexpression. Constitutive activation of the ACTH receptor-G protein-cAMP signal cascade does not play a role in adrenal tumour formation. Conversely, deletions of the ACTH receptor gene have recently been found in undifferentiated adenomas and in aggressive adrenocortical carcinomas, and, more recently, confirmed in a larger series of tumours. The available literature indicates that the signalling pathways of adrenocortical tumours are different from those of other endocrine neoplasms, such as pituitary and thyroid adenomas.

Adenomatous Polyposis Coli↗

PubMed1996

Whole-cell conductive properties of rat pancreatic acini.

Acetylcholine-controlled exocrine secretion by pancreatic acini has been explained by two hypotheses. One suggests that NaCl secretion occurs by secondary active secretion as has been originally described for the rectal gland of Squalus acanthias. The other is based on a "push-pull" model whereby Cl- is extruded luminally and sequentially taken up basolaterally. In the former model Cl- uptake is coupled to Na+ and basolateral K+ conductances play a crucial role, in the latter model, Na+ uptake supposedly occurs via basolateral non-selective cation channels. The present whole-cell patch-clamp studies were designed to further explore the conductive properties of rat pancreatic acini. Pilot studies in approximately 300 cells revealed that viable cells usually had a membrane voltage (Vm) more hyperpolarized than -30 mV. In all further studies Vm had to meet this criterion. Under control conditions Vm was -49 +/- 1 mV (n = 149). The fractional K+ conductance (fK) was 0.13 +/- 0.1 (n = 49). Carbachol (CCH, 0.5 micromol/l) depolarized to -19 +/- 1.1 mV (n = 63) and increased the membrane conductance (Gm) by a factor of 2-3. In the seeming absence of Na+ [replacement by N-methyl-D-glucamine (NMDG+)] Vm hyperpolarized slowly to -59 +/- 2 mV (n = 90) and CCH still induced depolarizations to -24 +/- 2 mV (n = 34). The hyperpolarization induced by NMDG+ was accompanied by a fall in cytosolic pH by 0.4 units, and a very slow and slight increase in cytosolic Ca2+. fK increased to 0.34. The effect of NMDG+ on Vm was mimicked by the acidifying agents propionate and acetate (10 mmol/l) added to the bath. The present study suggests that fK makes a substantial contribution to Gm under control conditions. The NMDG+ experiments indicate that the non- selective cation conductance contributes little to Vm in the presence of CCH. Hence the present data in rat pancreatic acinar cells do not support the push-pull model.

Animals↗