PubMed Health⌕ Search

Biomedical subjects

S Diederich

Publications and source records attributed to S Diederich.

At least 19 recordsLinked to original sources

Adiponectin oligomers in human serum during acute and chronic exercise: relation to lipid metabolism and insulin sensitivity.

Beneficial effects of physical exercise include improved insulin sensitivity, which may be affected by a modulated release of adiponectin, which is exclusively synthesized in white adipose tissue and mediates insulin sensitivity. Adiponectin circulates in three different oligomers, which also have a distinct biological function. We therefore aimed to investigate the distribution of adiponectin oligomers in human serum in relation to physical activity. Thirty-eight lean and healthy individuals were investigated. Seven healthy women and 8 healthy men volunteered to investigate the effect of chronic exercise, at 3 different time points with different training intensities. These individuals were all highly trained and were compared to a control group with low physical activity (n = 15). For studying acute exercise effects, 8 healthy men participated in a bicycle test. Adiponectin was determined by ELISA, oligomers were detected by non-denaturating western blot. Total adiponectin and oligomers were unchanged by acute exercise. LDL cholesterol was significantly lower in the chronic exercise group (p = 0.03). Total adiponectin levels and oligomers were not different between these two groups and were unaltered by different training intensities. However, total adiponectin and specifically HMW oligomers correlated with HDL cholesterol (r = 0.459; p = 0.009). We conclude that acute and chronic exercise does not directly affect circulating adiponectin or oligomer distribution in lean and healthy individuals. Whether such regulation is relevant in individuals with a metabolic disorder remains to be determined. However, our data suggest that adiponectin oligomers have distinct physiological functions IN VIVO, and specifically HMW adiponectin is closely correlated with HDL cholesterol.

Adiponectin↗

Solitary pulmonary nodule: detection and management.

Pulmonary nodules are commonly detected at computed tomography (CT) of the chest. More than 95% are < or = 10 mm; of these more than 95% are benign. Visual detection of pulmonary nodules by human readers is suboptimal, particularly with small nodules < or =10 mm. Computer-assisted detection can improve sensitivity and diagnostic confidence. Due to the high proportion of malignant lesions in nodules >10 mm immediate, often invasive workup is required including contrast-enhanced dynamic CT, positron emission tomography (PET) or biopsy. However, in nodules < or =10 mm the high proportion of benign lesions requires a non-invasive work-up usually based on follow-up with unenhanced CT. Invasive procedures are only required for growing nodules. Stable nodules require further follow-up and decreasing nodules are considered benign.

Adenocarcinoma↗

Application of a single needle type for all image-guided biopsies: results of 100 consecutive core biopsies in various organs using a novel tri-axial, end-cut needle.

PURPOSE: To assess feasibility, results and complications in image-guided biopsies using a single needle design in various organs. MATERIALS AND METHODS: 100 consecutive percutaneous biopsies were performed in 54 females and 46 males aged 24-87 years (mean age/standard deviation: 64.5 +/- 12 years) using a full-core end-cut tri-axial full-automatic biopsy needle (18 gauge BioPince, InterV-MDTech, Gainesville, Florida) under CT (n = 45) or ultrasound (n = 55) guidance. In 63 biopsies a coaxial technique was used. RESULTS: Biopsies were obtained of liver (n = 32), lymph nodes (n = 17), thyroid (n = 11), lung (n = 9), adrenal (n = 9), pelvis (n = 6), chest wall/pleura (n = 6), mediastinum (n = 4), lytic bone lesions (n = 2), retroperitoneum (n = 1), muscle (n = 1), pancreas (n = 1), peritoneum (n = 1). Between 1 and 6 (mean/SD 2.83 +/- 0.92) needle passes were performed. In 77 cases a malignant (40 metastases, 37 primary tumours) and in 23 a benign lesion was diagnosed. Of the 23 benign lesions a specific diagnosis was possible in 22. In one case necrosis and haemorrhage was diagnosed. In this patient surgery and autopsy both revealed a mediastinal haematoma of unknown origin. Eight minor complications (mild pain/local haematoma requiring no therapy) and three major complications (three pneumothoraces in nine lung biopsies requiring two aspirations and one drainage) were observed. There was no mortality. CONCLUSION: Percutaneous image-guided biopsy using the described full-core end-cut needle resulted in a specific diagnosis in 99/100 consecutive biopsies in various organs with a low complication rate. We use this needle type for all CT- or US-guided biopsies in all organs except for solid bone.

Adult↗

Free fatty acids increase androgen precursors in vivo.

CONTEXT: There is considerable evidence that metabolic factors such as insulin resistance may induce hyperandrogenemia in polycystic ovary syndrome. However, other metabolic factors such as free fatty acids (FFAs) may also contribute to androgen excess. OBJECTIVE: The objective was to study effects of FFAs on adrenal production of androgen precursors in vivo. DESIGN AND PARTICIPANTS: We investigated eight healthy young men, because male individuals produce the androgen precursors dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione predominantly in the adrenal gland. A randomized controlled crossover trial was performed. INTERVENTION: After a 10-h overnight fast, 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5 ml/min. Four hours after start of lipid infusion, a euglycemic hyperinsulinemic clamp was performed. MAIN OUTCOME MEASURES: DHEA, androstenedione, 17-OH-progesterone, testosterone, estrone, LH, FSH, ACTH, and cortisol were measured. RESULTS: The adrenal androgen precursors DHEA and androstenedione showed a circadian decline during saline/heparin infusion (P < 0.05 vs. baseline, respectively), whereas no significant changes were observed during lipid/heparin infusion (P = not significant vs. baseline, respectively). Correspondingly, DHEA and androstenedione values were significantly elevated during lipid compared with saline infusion (P < 0.05, respectively), and areas under curve of both androgen precursors were significantly increased with lipid compared with saline infusion. Notably, all changes were detected before induction of insulin resistance. CONCLUSIONS: This study demonstrates that FFAs increase production of androgen precursors in vivo in men. These data tentatively suggest that hyperandrogenemia in polycystic ovary syndrome may be induced, at least in part, by elevated FFAs.

17-alpha-Hydroxyprogesterone↗

[Pulmonary tumors].

Pulmonary nodules may be caused by true neoplasms of the airways, respiratory epithelium, vessels and connective tissue which are mainly malignant or metastatic. They may, however, also represent mainly inflammatory benign pseudotumours. Non-small cell lung cancer (NSCLC) usually presents as an ill-defined soft-tissue pulmonary nodule or mass, often without lymphadenopathy; endobronchial lesions are less common. Small cell lung cancer (SCLC) commonly presents with extensive lymph node and hematogenous metastases. Carcinoid tumors typically manifest as endobronchial lesions with secondary obstruction. Sarcomas are rare and show variable morphology. Metastases most commonly present as basal, peripheral, well-defined nodules. Granulomas often exhibit typical calcifications; hamartoma may also contain popcorn-type calcifications as well as fat. Pulmonary arteriovenous malformation is characterised by feeding artery and draining vein. Inflammatory nodules are well vascularized and may regress spontaneously; their differentiation from malignant lesions, however, is usually difficult.

Carcinoma, Non-Small-Cell Lung↗

Solitary pulmonary nodule with growth and contrast enhancement at CT: inflammatory pseudotumour as an unusual benign cause.

Small (< or =10 mm) pulmonary nodules are frequently detected at modern chest CT. As most of these nodules are benign, non-invasive classification is required--usually based on assessment of growth and perfusion. Absence of growth and no evidence of perfusion, as demonstrated by lack of enhancement at contrast-enhanced CT or MRI, strongly suggest a benign nodule. On the other hand, growth with a doubling of the nodule's volume between 20 days and 400 days or enhancement suggest a malignant nature of the lesion. We present an example of a nodule with strong contrast enhancement and a doubling time of approximately 260 days, which histologically represented a benign inflammatory pseudotumour.

Diagnosis, Differential↗

Resolving small pulmonary nodules: CT features.

Our aim was to analyse the CT morphology of resolving nodules over time in order seek morphologic features helpful in initial nodule classification. The imaging characteristics of 133 consecutive resolving pulmonary nodules detected in 56 subjects in a screening trial for early lung cancer with low-dose CT were retrospectively reviewed by two readers in consensus. Nodule size ranged from 2 to 28 mm, with a mean diameter of 5.9 mm. The maximum diameter of resolving nodules was < or =5 mm in 71/133 (53%), 6-10 mm in 52/133 (39%), and >10 mm in 10/133 (8%). Their location was mainly peripheral, with a mean distance to the costal pleura of 10 mm. There was no lobe predominance of nodules. In 85% (113/133) of cases the nodules were solid, 77% (103/133) were well-defined, and 73% (97/133) were non-lobulated. Eighty percent (107/133) resolved completely within 14-1,671 (mean 492) days, 20% (26/133) resolved incompletely with residual abnormalities within 51-1,777 (mean 613) days. Resolving pulmonary nodules were mostly < or =10 mm, peripherally located, solid, well-defined, and non-lobulated. Most resolve completely within a variable interval ranging from several days to years.

Adult↗

[Lung cancer screening -- state of the art].

Besides smoking as the main risk factor for lung cancer several occupational risk factors like exposure to asbestos, polycyclic aromatic hydrocarbons, uranium and dust containing nickel or silica have to be considered. Due to lack of effort in smoking prevention and cessation, lung cancer screening is an important issue. A number of pitfalls has to be considered when evaluating the efficacy of screening procedures. In this paper, we summarize the results of the major studies including chest X-ray, sputum cytology and low dose computed tomography. Randomized controlled studies involving low dose CT in about 100 000 subjects are on the way. Around the year 2010 we will be able to define whether or not lung cancer screening including new techniques and standardized algorithms yields a decrease in mortality. If diagnostic algorithms are used which have been applied in published feasibility studies, the mean percentage of invasive diagnostic measures revealing benign lesions is about 34 % and thus below those obtained in, e. g., breast cancer screening trials.

Germany↗

In vivo activity of 11beta-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance.

INTRODUCTION: Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels. METHODS: Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. RESULTS: Lipid infusion increased FFAs (5.41 +/- 1.00 vs. 0.48 +/- 0.20 mmol/l; P < 0.005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6.02 +/- 2.60 vs. 4.08 +/- 2.15 mg/kg/min; P < 0.005]. After lipid and saline infusions no changes in 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios. CONCLUSIONS: We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

Adaptation of the hypothalamic-pituitary hormones during intensive endurance training.

OBJECTIVE: Physical activity leads to changes in the hypothalamic-pituitary hormonal system. However, acute and long-term adaptations have not yet been precisely characterized. In this study, the changes of the hormonal system as a result of marathon training and running a marathon were examined. In particular, we focused on adaptations of the hypothalamic-pituitary-adrenocortical (HPA) axis, regarding the activation or inactivation of cortisol to cortisone by the 11beta-hydroxysteroid-dehydrogenase system (11beta-HSD). DESIGN: Patient measurements: 8 healthy women and 11 healthy men volunteered for this study. Blood samples, 24-h urine and a dexamethasone suppression test were analysed for metabolic and hormonal parameters at five different dates 12 weeks around a marathon. RESULTS: Cortisol and ACTH values decreased significantly 2 days after the marathon, whereas the activity of the whole body 11beta-HSD-1 was up-regulated. An increased suppression of cortisol levels was observed in the dexamethasone suppression test after 6 weeks of reduced training levels. Ghrelin was elevated 2 days after the marathon. Only minor changes in the other hypothalamic-pituitary-hormonal axes could be observed. However, the free androgen index increased significantly after 6 weeks of reduced training. CONCLUSIONS: The HPA system appeared to become chronically activated by continuous physical training and therefore less sensitive to the dexamethasone suppression test. The acute stress of the marathon led to a central exhaustion of the HPA system with a paracrine counteraction by the activation of the 11beta-HSD system. Changes in the other hypothalamic-pituitary hormonal axes were the result of long-term differences in training levels and were not altered by the marathon.

Adaptation, Physiological↗

Glucagon inhibits ghrelin secretion in humans.

OBJECTIVE: It is well known that i.m. glucagon administration stimulates GH and cortisol release in humans, although the mechanisms are unclear. These effects are similar to those described for ghrelin on somatotroph and corticotroph function. The aim of the present study was to investigate the role of ghrelin in mediating the stimulatory effects of glucagon and to evaluate the effect of glucagon on ghrelin secretion. DESIGN AND METHODS: We studied the endocrine and metabolic response to i.m. glucagon administration in 24 subjects (14 men, 10 women; age 19-65 years; body mass index, 25.3 +/- 1 kg/m(2)), who were shown to have an intact anterior pituitary function as evaluated before enclosure. RESULTS: Serum ghrelin concentrations fell significantly at 30, 60, 120 and 180 min after glucagon administration (means +/- s.e.m.; baseline, 377.9 +/- 34.5 pg/ml; nadir, 294.6 +/- 28.3 pg/ml (60 min); P < 0.01). Conversely, i.m. glucagon elicited an increase in GH (baseline, 1.5 +/- 0.4 microg/l; peak, 14.2 +/- 2.7 microg/l (180 min); P < 0.01) and cortisol concentrations (baseline, 452.6 +/- 35.2 nmol/l; peak, 622.1 +/- 44 nmol/l (180 min); P < 0.01). The changes in ghrelin concentration at both 120 and 180 min were still significant after correction for glucose and insulin (P < 0.05). CONCLUSIONS: We show that i.m. glucagon decreases ghrelin significantly. Therefore, the already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations. The mechanisms underlying the ghrelin suppression after i.m. glucagon are unlikely to include glucose or insulin variations and need to be further elucidated.

Adult↗

[Percutaneous ablation of pulmonary tumours: state-of-the-art 2004].

Percutaneous radiofrequency ablation (RFA) and laser-induced interstitial thermotherapy (LITT) are well established since many years in liver and other soft tissue tumors. During the past 2 years there are increasing reports on applications in pulmonary tumors. There are, however, numerous differences to ablations in other organs: indications in pulmonary metastases and lung cancer have to be balanced against the specific possibilities of well-established surgical resections. Tissue specific features require different concepts of energy deployment and complications and methods for assessment of therapeutic effectiveness vary from other applications. Other aspects, however, are quite clear, yet. There are specific established indications particularly for thermoablation of pulmonary metastases. Tumor ablation is easily performed by experienced interventional radiologists and serious complications are rare. Patient acceptance is good. Further studies are required on indications, technical requirements, therapy control and particularly long-term results.

Carcinoma, Bronchogenic↗

[Radiological diagnosis of pulmonary metastases: imaging findings and diagnostic accuracy].

Pulmonary metastases typically present as mostly multiple and bilateral, well-defined, non-calcified pulmonary nodules with predominantly basal and peripheral location. Ill-defined, cavitating, calcified and endobronchial metastases are uncommon. In the absence of pathognomonic findings precise differentiation from other-even benign-pulmonary nodules is almost impossible. Demonstration of contrast enhancement at CT or MRI or evidence of growth at serial examinations support the diagnosis of pulmonary metastases. In uncertain cases percutaneous fine-needle aspiration or cutting needle biopsy will allow diagnosis with acceptable risk of complications and patient discomfort. The only relatively common complication of pneumothorax can and should be controlled by the interventional radiologist by aspiration or drainage.

Biopsy↗

Diagnostic performance of a commercially available computer-aided diagnosis system for automatic detection of pulmonary nodules: comparison with single and double reading.

OBJECTIVE: To assess the diagnostic performance of a commercially available computer-aided diagnosis (CAD) system for automatic detection of pulmonary nodules with multi-row detector CT scans compared to single and double reading by radiologists. MATERIALS AND METHODS: A CAD system for automatic nodule detection (Siemens LungCare NEV VB10) was applied to four-detector row low-dose CT (LDCT) performed on nine patients with pulmonary metastases and compared to the findings of three radiologists. A standard-dose CT (SDCT) was acquired simultaneously and used for establishing the reference data base. The study design was approved by the Institutional Review Board and the appropriate German authorities. The reference data base consisted of 457 nodules (mean size 3.9 +/- 3.1 mm) and was established by fusion of the sets of nodules detected by three radiologists independently reading LDCT and SDCT and by CAD. An independent radiologist used thin slices to eliminate false positive findings from the reference base. RESULTS: An average sensitivity of 54 % (range 51 % to 55 %) was observed for single reading by one radiologist. CAD demonstrated a similar sensitivity of 55 %. Double reading by two radiologists increased the sensitivity to an average of 67 % (range 67 % to 68 %). The difference to single reading was significant (p < 0.001). CAD as second opinion after single reading increased the sensitivity to 79 % (range 77 % to 81 %), which proved to be significantly better than double reading (p < 0.001). CAD produced more false positive results (7.2 %) than human readers but it was acceptable in clinical routine. CONCLUSION: Double reading with CAD as second reader offered a significantly increased sensitivity compared to conventional double reading. Thus, CAD is a valuable tool for the detection of pulmonary nodules and should be used as second opinion.

Adult↗

The role of progesterone metabolism and androgen synthesis in renal blood pressure regulation.

11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a crucial role in converting hormonally active cortisol into inactive cortisone, conferring specificity onto the human mineralocorticoid receptor (MR). Progesterone binds with even higher affinity to the MR, but acts as an MR antagonist. How aldosterone is able to keep its function as predominant MR ligand in clinical situations with high progesterone concentrations, such as pregnancy, is not clear. We have shown in vitro that the human kidney possesses an effective enzyme system that metabolizes progesterone to inactive metabolites in a process similar to the inactivation of cortisol by 11beta-HSD2. In studies on patients with adrenal insufficiency, we have shown that the in vivo anti-mineralocorticoid activity of progesterone is diminished by inactivating metabolism of progesterone, local formation of the deoxycorticosterone mineralocorticoid from progesterone, and inhibition of 11beta-HSD2 by progesterone and its metabolites resulting in decreased inactivation of cortisol and hence increased MR binding by cortisol. The enzymes involved in progesterone metabolism are also responsible for the capability of the human kidney to convert pregnenolone to DHEA and androstenedione leading to the formation of active androgens, testosterone and 5alpha-DH-testosterone. Locally produced androgens might be responsible for the observed difference in blood pressure between men and women and higher susceptibility to hypertension in men.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

Pharmacodynamics and pharmacokinetics of synthetic mineralocorticoids and glucocorticoids: receptor transactivation and prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases.

Glucocorticoid (GC) and mineralocorticoid (MC) action in target tissues is determined by prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases (HSDs) and receptor transactivation. We characterized these parameters for steroids often used in clinical practice. HSD activity was examined in human liver (HSD1) and kidney microsomes (HSD2) and in CHO cells stably transfected with both enzymes. GC and MC transcriptional activity was tested by luciferase assay in CV-1 cells transfected with human GC or MC receptor expression vectors. The 11-hydroxy-group is necessary for GC and MC receptor transactivation. As HSD2 oxidizes 11-hydroxysteroids to inactive 11-dehydrosteroids, GC and MC activity in HSD2-expressing tissues (kidney, colon) is regulated by this enzyme. As 9alpha-fluorination (such as in 9alpha-fluorocortisol) decreases oxidation by HSD2 and increases both GC and MC receptor transactivation, this modification leads to optimal, but non-selective transactivation of both receptors. Increased GC receptor and decreased MC receptor transactivation leading to more selective GC activity is reached using the following substituents: 16beta-methyl (in betamethasone), 16alpha-methyl (in dexamethasone) and triangle up 1-dehydro-configuration (in prednisolone). Whereas the modifications in position 16 decrease oxidation by HSD2, the triangle up 1-dehydro-configuration increases HSD2-activity leading to an enhanced inactivation of prednisolone compared to all other steroids. 9alpha-fluorocortisol, the most frequently used substance for MC-substitution, seems to be the best choice of available steroids for this purpose. Whereas GC selectivity can be improved by hydrophobic substituents in position 16 and the triangle up 1-dehydro-configuration, maximal GC activity needs additional fluorination in position 9alpha (such as in dexamethasone). For GC therapy directed to HSD2-expressing organs, widely used prednisolone does not seem to be the optimal recommendation.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans.

OBJECTIVE: The orexigenic and adipogenic peptide hormone ghrelin is predominantly produced and secreted by the stomach and seems to transduce changes in food intake to specific neuronal circuits in the brain. The activity of ghrelin also includes stimulatory effects on the corticotropic system. However, little is known about the influence of glucocorticoids on ghrelin levels. We therefore studied human plasma ghrelin levels in the presence and absence of elevated glucocorticoid levels of either endogenous or exogenous origin. METHODS: Plasma ghrelin levels were measured in five patients with chronic hypercortisolism (aged 29-58, median 46 years) due to Cushing's syndrome before and after successful surgery for the adenoma, and in eight healthy controls (aged 24-39, median 27.5 years) before and after 30 mg prednisolone (for 5 days) once a day in the morning (median body mass index (BMI) 22.7 kg/m(2)). Plasma ghrelin levels were measured with a commercially available radioimmunoassay. RESULTS: In patients with Cushing's syndrome, plasma ghrelin levels were low (median 363.2 pg/ml, range 161.9-525.7 pg/ml) and significantly increased by 26.6% (P=0.04) after successful surgery, while BMI decreased (median 26.2-24.0 kg/m(2), P=0.04). A strong negative correlation (r=-0.9, P=0.04) between changes in BMI and plasma ghrelin was observed. In healthy controls, plasma ghrelin levels (median 288.7 pg/ml, range 119.6-827.8 pg/ml) were significantly suppressed by 18.3% (P=0.04) after prednisolone treatment. CONCLUSIONS: We have shown for the first time that plasma ghrelin levels are decreased under endogenously or exogenously induced hypercortisolism, making ghrelin an unlikely candidate for causing the changes in energy balance or body composition characteristic of Cushing's disease. However, the reduced ghrelin secretion could reflect a compensation mechanism in reaction to the metabolic consequences of chronic hypercortisolism.

Adult↗