Inhibition of human adrenal androgen secretion by ketoconazole

Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.Abbreviations CV coefficient of variation - MV mean value - SEM standard error of the mean - f female - m male - K ketoconazole - ACTH adrenocorticotropic hormone - DHEA dehydroepiandrosterone - DHEAS dehydroepiandrosterone sulfate - A androstenedione - T testosterone - F cortisol - P progesterone - H hirsutism - C Cushing's disease - EAS ectopic ACTH syndrome - ATU adrenal tumor     

Relation between plasma fibroblast growth factor-23, serum fetuin-A levels and coronary artery calcification evaluated by multislice computed tomography in patients with normal kidney function

Objective To examine the correlation of plasma fibroblast growth factor (FGF)‐23 and serum fetuin A levels with the coronary artery calcification score (CACS) in patients with normal kidney function. Background Vascular calcification is an active process that may be aggravated by hyperphosphataemia and hypercalcaemia. FGF‐23 and human fetuin‐A have been associated with calcifying arteriosclerosis in renal failure. Plasma FGF‐23 was identified as an independent factor negatively associated with peripheral vascular calcification. Fetuin‐A acts as a systemic inhibitor of ectopic calcification in dialysis patients and can be correlated to the survival of these patients. Very few data exists on the role of FGF‐23 and fetuin‐A in coronary calcification of patients without impaired kidney function. Materials and methods Sixty‐four patients, 21 females and 43 males, were subjected to 64‐slice coronary computed tomography (CT) to evaluate coronary artery calcification (CAC). Plasma intact FGF‐23 was determined by ELISA. Serum fetuin‐A concentration were evaluated nephelometrically. Results Mean plasma FGF‐23 level was 20·4 ± 9·1 pg/ml and serum fetuin‐A was 0·46 ± 0·09 g/l. There was no correlation between FGF‐23 (P = 0·777) and fetuin‐A (P = 0·767) levels and the CACS. No correlation was found between the presence of noncalcified plaques and coronary artery stenosis (CAS) ≥  50%, and FGF‐23 (P = 0·313 and P = 0·775) and fetuin‐A levels (P = 0·601 and P = 0·659). Conclusion Plasma intact FGF‐23 and serum fetuin‐A concentration do not correlate with the CACS, the grade of stenosis or presence of noncalcified plaques of the coronary arteries in patients with normal kidney function.     

Attitudes of Health Care Professionals towards Female Obese Patients

ObjectiveThe health care setting has been reported to be one main source of weight stigma repeatedly; however, studies comparing different professions have been lacking.Methods682 health care professionals (HCP) of a large German university hospital were asked to fill out a questionnaire on stigmatizing attitudes, perceived causes of obesity, and work-related impact of obesity. Stigmatizing attitudes were assessed on the Fat Phobia Scale (FPS) based on a vignette describing a female obese patient.ResultsOnly 25% graded current health care of obese patients to be ‘good’ or ‘very good’. 63% of all HCPs ‘somewhat’ or ‘strongly’ agreed that it was often difficult to get the resources needed in order to care for obese patients. The mean FPS score was comparable to that in the general public (M = 3.59), while nursing staff showed slightly more positive attitudes compared to physicians and therapists. Higher age, higher BMI, and ascribing personal responsibility for obesity to the individual were associated with a higher level of stigmatizing attitudes. The nursing staff agreed on obesity as an illness to a greater extent while physicians attributed obesity to the individual.ConclusionsIn summary, by making complex models on the causes of obesity known among health care professionals, stigmatizing attitudes might be reduced. Ongoing further education for health care professionals ought to be part of anti-stigma campaigns in the medical field.Key Words: Health care professionals, Obesity, Care, Stigma     

Attitudes Towards Bariatric Surgery in the General Public

Background

Prevalence rates of obesity are still rising. Weight loss surgery (WLS) is the most invasive but also most effective treatment option when behavioral modification has failed. Research indicates that health care professionals hold ambivalent views on bariatric surgery, while views of the general public have not yet been investigated.

Methods

In a German representative sample of n?=?3,003 respondents in a computer-assisted telephone interview, n?=?1,008 persons were interviewed on their views of the effectiveness of bariatric surgery and other interventions for obesity. Also, willingness to recommend a treatment was assessed.

Results

Lifestyle-based interventions were viewed as most effective in terms of weight loss. About 50 % of the population stated that WLS is “very effective” while still a quarter of respondents did not ascribe effectiveness to WLS. Higher age was associated with lower expectations of effectiveness while higher stigmatizing attitudes and genetic attributes for obesity were associated with higher expectations of effectiveness. Seventy-two percent would not recommend WLS or undergo it, if applicable, themselves. Higher educated respondents and those that viewed WLS as effective were more likely to recommend WLS.

Conclusions

The German general public seems to be rather cautious regarding bariatric surgery. It may be assumed that false beliefs on the effectiveness and risk patterns of bariatric surgery are still very common, despite rising surgery numbers. Our results further emphasize the need for providing evidence-based information on bariatric surgery to the general public.     

Prognosis of Mild Cognitive Impairment in General Practice: Results of the German AgeCoDe Study

PURPOSE

The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients).

METHODS

We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis.

RESULTS

Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis.

CONCLUSIONS

In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.     

Clinical significance of allergic reactions in glucocorticoid therapy

BACKGROUND: Glucocorticoids are widely used in medicine. Within the last few years, however, patients have become very suspicious of corticoids. The attending physicians frequently has to use a great deal of persuasion prior to applying this very effective and often indispensable group of medication. PATIENTS: We report on four patients who developed allergic reactions (i.e. erythema in face and on body, itching, flushing, drop in blood pressure, respiratory distress, cold sweats, etc.) immediately after intravenous administration of prednisolone-21 hydrogen succinate (Solu-Decortin H, SDH). RESULTS: Three out of four patients had a positive reaction to an intracutaneous test with SDH, but no reaction to the additive sodium succinate. The prick test was negative in all patients. No specific IgE antibodies were detected in the serum of these patients. However allergic reaction to SDH must be presumed in at least three cases as it is difficult to detect glucocorticoid antibodies in serum and standardizes techniques are lacking. One female patient had a cross-reaction to prednisolon and dexamethasone. A renewed application of SDH was tolerated well by all patients when H1- and H2-receptors were blocked and calcium was administered to stabilize membranes. CONCLUSIONS: Allergic reactions after glucocorticosteroid therapy are only occasionally mentioned in literature, appear more often when the agent is applied topically, and may lead to dangerous complications in patients if administered intravenously. Therefore, when allergic reactions result from glucocorticoid therapy (immediate reactions should be suspect), corticosteroid allergy should be considered as a differential diagnosis.     

Clinical value of cystatin C determination

It has been reported that cystatin C (cys-C) is elevated in patients with malignant disease. In order to investigate whether this phenomenon is linked to or independent of renal function, and at the same time examine the role of this marker in other pathological situations, cys-C concentrations were compared with 24-h creatinine clearance values in three groups of patients; the first group were undergoing treatment for malignant disease, the second group were renal transplant patients and the third randomly taken from patients for whom a routine creatinine clearance had been requested. Several patients with malignant disease had high cys-C levels without any correspondence to creatinine clearance values. Additionally, although cys-C shows a high sensitivity for detecting impaired glomerular function in renal transplant patients, the specificity was very low, with little discrimination being observed between patients with normal and pathological creatinine clearance levels. In other patients both the sensitivity and specificity of cys-C could be shown to be very good. Thus although cys-C can generally be recommended as a marker of the glomerular filtration rate, there are some patients for whom the clinical relevance is unclear.     

Biosensor analysis of beta2-glycoprotein I-reactive autoantibodies: evidence for isotype-specific binding and differentiation of pathogenic from infection-induced antibodies

BACKGROUND: For the laboratory diagnosis of the antiphospholipid syndrome (APS) we developed a biosensor with the ability to distinguish between disease-relevant anti-beta2-glycoprotein I (beta2GPI) autoantibodies (anti-beta2GPI) and pathogen-specific beta2GPI cross-reactive antibodies that occur transiently during infections. METHODS: We used a surface plasmon resonance (SPR) biosensor device. For the detection of anti-beta2GPI in serum samples, affinity-purified human beta2GPI was covalently attached to a functionalized n-alkanethiol self-assembling monolayer on the biosensor chip. After verifying the specificity of the biosensor system with a panel of monoclonal antibodies to beta2GPI, we analyzed sera from healthy donors and patients suffering from APS, systemic lupus erythematosus (SLE), syphilis, or parvovirus B19 infections. The SPR results were compared with beta2GPI-specific ELISA. RESULTS: Using the SPR biosensor, we recorded antigen binding curves with response levels in the range of 50-500, resonance units (RU) for anti-beta2GPI ELISA-positive APS patient sera. The amplitudes of the antiphospholipid antibody (APL) responses in the biosensor correlated with the overall IgG and IgM anti-beta2GPI ELISA titers with a correlation coefficient of 0.87. Moreover, we observed immunoglobulin isotype-specific association and dissociation profiles for APL binding of different APS patient sera to the biosensor-immobilized beta2GPI. In contrast to APS patient samples, no significant anti-beta2GPI binding (response levels <35 RU) was observed in samples from healthy individuals or from patients suffering from SLE, syphilis, or parvovirus B19 infection. CONCLUSIONS: The SPR biosensor system enables specific detection of APS-associated beta2GPI-reactive APL and differentiation from beta2GPI cross-reactive antibodies that occur frequently during acute infections. The established association/dissociation plot for anti-beta2GPI responses in APS patient sera gives additional information regarding the influence of anti-beta2GPI IgG and IgM isotype distribution.