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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 37 records · Page 2Linked to original sources

[Diabetes update: preventing type 2 diabetes. Individualized stepwise therapy (oral antidiabetic agents). Multifactorial intervention].

Preclinical disorders of glucose metabolism should be systematically included in the high-risk group for diabetes mellitus and affected individuals provided with preventive measures. Their underlying insulin resistance is determined with the help of a checklist and a method called homeostasis model assessment (HOMA). Patients with impaired fasting glucose (IFG) must change their lifestyles. If this does not lead to a response or the patient is unable to modify behavior, medication is required. In the case of manifest type 2 diabetes mellitus, a graded schedule is used for differential management, which should be based on nutritional and exercise therapy. Oral medication with metformin is probably the drug of choice in both obese and non-obese patients. It is crucial not to delay raising the level of treatment until HbA1c has fallen to within an unsatisfactory range (wait-and-see strategy). Rather, the level should be intensified when persistent exacerbation starts to become apparent (proactive therapy). In diabetes mellitus, the same guidelines for secondary prevention apply to the associated cardiovascular risk factors as with coronary heart disease. An intensified and, especially, early treatment is to be preferred over a conservative, wait-and-see approach, in this case as well.

Cardiovascular Diseases↗

Comparison of different methods for the measurement of serum testosterone in the aging male.

BACKGROUND: Circulating testosterone (T) levels, mainly non-SHBG bound fractions, decline with advancing age. Free (FT) and bioavailable (BT) testosterone levels have been suggested to represent more reliably the bioactive hormone at the tissue level as compared to total testosterone (TT) levels. However, there is an ongoing controversy as to which T assay is most appropriate in defining T deficiency in the aging male. METHODS: In a prospective observational study, TT, FT and BT levels were measured in 51 elderly men (55 to 70 years). TT levels were determined on two different days using 2 different assays. FT was calculated using TT, albumin and SHBG levels as well as measured directly by radioimmunoassay. The free androgen index (FAI) was calculated using the formula 100 x TT/SHBG. BT was obtained by precipitation of SHBG-bound T with ammonium sulphate. RESULTS: We found good correlations within different assays for TT (r = 0.87 to 0.91, p <0.001) and between TT and calculated FT (r = 0.66 to 0.84, p <0.001). In contrast, the correlation between TT and BT was poor (r = 0.17 to 0.19, p = ns). TT was equivalent to calcFT and was better in mirroring clinical sings of androgen deficiency in elderly men as compared to BT. The intra-individual day-to-day variance of TT levels was 14.8% (range 0.1-79%) with a coefficient of variance of 12.6%. CONCLUSION: Serum TT and the calculated FT fraction correlated well with each other and were superior in defining a group of elderly men with suspected androgen deficiency. In contrast, FT measured by direct RIA and BT reflected gonadal function poorly. Our data favour the repetitive use of TT when screening for androgen deficiency in elderly men.

Aged↗

[Effect of antipsychotics on glutaminergic neural transmission in the animal model].

Post-mortem investigations have confirmed that glutamatergic NMDA, AMPA, and kainate receptors are involved in the pathophysiology of schizophrenia. It is still unclear, however, whether the altered number of receptors is caused by the disease itself or the medication. Therefore, animal models were investigated for effects of antipsychotic medication after treatment periods of up to 6 months, the results of which are summarized here. Generally, NMDA receptor binding was found to be increased in striatum and nucleus accumbens after therapy with haloperidol, whereas clozapine only increased the number of receptors in nucleus accumbens. While haloperidol led to an increase in AMPA receptors in the posterior cingulate gyrus, striatum, insular cortex, and n. accumbens, clozapine was found to elevate ligand binding in the anterior cingulate gyrus and infralimbic cortex. Although kainate receptor binding was increased in hippocampus by both antipsychotics, clozapine was significantly more effective. In conclusion, data reveal different effects from the typical neuroleptic haloperidol and the atypical antipsychotic clozapine. The results suggest that post-mortem findings in patients with schizophrenia may at least partially be explained by drug effects and plasticity changes induced by long-term medication with antipsychotics.

Animals↗

Overweight and obesity in children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Epidemiological studies suggest that adiposity in children may be associated with a reduced level of physical activity. Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are physically hyperactive as of early childhood and have been shown to exhibit higher levels of motor activity than normal. The aim of our study was to assess if the prevalence of overweight and obesity is lower in a population of boys with ADHD in comparison with the German healthy male reference population of the same age. DESIGN: Patients were investigated from 1999 until 2001 upon referral to the inpatient and outpatient unit of the Department of Child and Adolescent Psychiatry of the University of Aachen. SUBJECTS: A total of 97 male patients (mean age 10+/-2 y) with a diagnosis of ADHD according the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), who were free of potentially orexigenic medication and who had no further comorbid diagnosis apart from conduct disorder. MEASUREMENTS: BMI standard deviation scores (BMI-SDS) were calculated and compared to age-adapted reference value of the German population. RESULTS: Patients' mean BMI-SDS was significantly higher than the age-adapted reference values of the German population (P=0.038). Our sample included significantly more subjects than expected with a BMI > or =90th percentile (19.6%, P<0.001) and > or =97th percentile (7.2%, P=0.007). CONCLUSION: Surprisingly, being 'hyperactive' in the sense of the DSM-IV diagnosis of ADHD does not prevent the development or persistence of overweight and obesity in children. The examination of these children might be a helpful approach in the investigation of the relationship between obesity and its contributing psychological and behavioural factors.

Adolescent↗

Polysaccharides from Hibiscus sabdariffa flowers stimulate proliferation and differentiation of human keratinocytes.

Raw polysaccharides, previously described in detail, were isolated from the flowers of Hibiscus sabdariffa L. and fractionated by ion exchange chromatography into one neutral and three acidic subfractions. Raw polysaccharides and all acidic subfractions caused a strong induction of proliferation of human keratinocytes (HaCaT) of up to 40 %, while the neutral polymers were ineffective. While mitochondrial activity was not influenced, raw polysaccharides induced early differentiation of primary natural human keratinocytes, as determined by involucrin formation.

Cell Division↗

Differential effects of long-term treatment with clozapine or haloperidol on GABA transporter expression.

BACKGROUND: Post-mortem studies with brain samples of schizophrenic patients led revealed altered GABA-ergic markers like reduced expression of the GABA transporter GAT-1. Whether this effect is due to the pathophysiology of schizophrenia or to antipsychotic treatment has not been investigated. We therefore established an animal trial of long-term antipsychotic treatment to address this question. METHODS: A total of 33 adult male rats were investigated in three cohorts of 11 animals. One group received clozapine (45 mg/kg/ day), another group haloperidol (1.5 mg/kg/day), and the third one pH-adapted water over a period of 6 months. In situ hybridization with cRNA probes specific for GABA transporters VGAT, GAT-1 and GAT-3 were performed in comparison to control animals. RESULTS: While GAT-1 was upregulated, VGAT expression declined in cortical and limbic brain regions, whereby haloperidol showed a greater effect than clozapine. GAT-3 expression was suppressed in parietal and temporal cortex. CONCLUSIONS: We thus conclude that long-term antipsychotic treatment alters GABA transporter expression in rat. The upregulation of GAT-1 contrasts with the post-mortem finding of reduced GAT-1 expression in schizophrenic patients. Our results facilitate the distinction between disease dependent changes of GABAergic markers and medication effects.

Amino Acid Transport Systems↗

Radioiodine therapy in hyperthyroidism: inverse correlation of pretherapeutic iodine uptake level and post-therapeutic outcome.

BACKGROUND: High iodine uptake levels are widely accepted as a condition for successful treatment with radioiodine (RAI). However, the existing data are controversial and the correlation of pretherapeutic RAI uptake level and outcome of RAI therapy has not yet been quantified. The aim of this study was to analyze the influence of RAI uptake on the outcome after RAI treatment and to estimate uptake-dependent success rates. MATERIALS AND METHODS: We retrospectively analyzed 229 patients (m = 53, f = 176; age 64 +/- 14 years) suffering from toxic adenoma, multinodular goitre or Graves' disease, respectively. Clinical status and T3, fT4 and TSH levels were assessed 3, 6, 12 and 18 months after treatment. Successful treatment was defined as loss of hyperthyroidism 18 months after radioiodine therapy. Logistic regression was used to assess the relation between the maximum iodine uptake and the rate of success and hypothyroidism, respectively, after RAI treatment. RESULTS: Overall, patients presented with pretherapeutic RAI uptake values between 17% and 100%. Eighteen months after RAI treatment, an euthyroid state was achieved in 136 patients (60%), hypothyroidism occurred in 47 patients (20%) and 46 patients (20%) remained hyperthyroid. The patients with the lowest pretherapeutic RAI uptakes showed the highest success rates. The overall success rate significantly decreased from 92% at low RAI uptakes to 57% at high uptakes (P = 0.002). This effect was found in the patients suffering from multinodular goitre as well as in the patients with Graves' disease. CONCLUSION: In contrast to the current opinion, our results provide evidence that the pretherapeutic iodine uptake level and post-therapeutic outcome are inversely correlated.

Adenoma↗

Effects of alcohol consumption on mortality in patients with Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Moderate alcohol intake has been associated with increased life expectancy due to reduced mortality from cardiovascular disease. We prospectively examined the effects of alcohol consumption on mortality in Type 2 diabetic patients in Switzerland. METHODS: A total of 287 patients with Type 2 diabetes mellitus (125 women, 162 men), recruited in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes, were included in this study. After a follow-up period of 12.6+/-0.6 years (means +/- SD), mortality from CHD and from all causes was assessed. RESULTS: During the follow-up, 70 deaths occurred (21 from CHD, 49 from other causes). Compared with non-drinkers, alcohol consumers who drank alcohol 1 to 15 g, 16 to 30 g and 30 g or more per day had the following risk rates of death from CHD: 0.87 (95% CI: 0.25 to 2.51, NS), 0.00 (95% CI: 0.00 to 0.92, p less than 0.05) and 0.37 (95% CI, 0.01 to 2.42, NS), respectively. The corresponding risk rates of death from all causes were 1.27 (95% CI: 0.68 to 2.28, NS), 0.36 (95% CI: 0.09 to 0.99, p less than 0.05) and 1.66 (95% CI: 0.76 to 3.33, NS). CONCLUSIONS/INTERPRETATION: In Swiss Type 2 diabetic patients moderate alcohol consumption of 16 to 30 g per day was associated with reduced mortality from CHD and from all causes. Alcohol intake above 30 g per day was associated with a tendency towards increased all-cause mortality.

Adult↗

[49-year-old patient with staphylococcal endocarditis and thyrotoxic crisis].

We report the case of a 49-year-old woman who presented with typical features of thyroid crisis. Besides the confirmation of severe thyreotoxicosis a native valve endocarditis due to Staphylococcus aureus was diagnosed. Diagnostic criteria and therapies of these life-threatening disorders are discussed and a possible association in the present case is evaluated.

Diagnosis, Differential↗

Hereditary myoclonus-dystonia associated with epilepsy.

A five-generation Dutch family with inherited myoclonus-dystonia (M-D) is described. Genetic analysis revealed a novel truncating mutation within the epsilon-sarcoglycan gene (SGCE). In three of five gene carriers, epilepsy and/or EEG abnormalities were associated with the symptoms of myoclonus and dystonia. The genetic and clinical heterogeneity of M-D is extended. EEG changes and epilepsy should not be considered exclusion criteria for the clinical diagnosis of M-D.

Adult↗

Hadronization in heavy-ion collisions: recombination and fragmentation of partons.

We argue that the emission of hadrons with transverse momentum up to about 5 GeV/c in central relativistic heavy ion collisions is dominated by recombination, rather than fragmentation of partons. This mechanism provides a natural explanation for the observed constant baryon-to-meson ratio of about one and the apparent lack of a nuclear suppression of the baryon yield in this momentum range. Fragmentation becomes dominant at higher transverse momentum, but the transition point is delayed by the energy loss of fast partons in dense matter.

Journal Article↗

[Weight loss cures advertised in the media: only quackery?].

Obesity is a multifactorial disease that afflicts a growing number of people in Europe and throughout the world. Both commercial and medical treatment programs are characterized by high rates of long-term recidivism. A cultural preoccupation with slimness has created a profitable industry serving millions of people who are attempting continually to reduce weight. This review summarizes the major areas of consensus and controversy concerning the health implications of obesity and weight loss and suggests novel directions for treatment.

Advertising↗

[Postoperative routine use of physostigmine on vigilance, cardiovascular parameters and need of analgesics].

OBJECTIVE: A central anticholinergic syndrome (CAS) can be related to the majority of anesthetic agents, but is often not recognized as such. Thus, most anesthesiologists seem to miss the occurrence of an anticholinergic syndrome especially when agitation and/or restlessness are the major symptoms. Therefore, the following study was undertaken to test the hypothesis that routine administration of the anticholinergic agent physostigmin is of benefit for patients in regard to vigilance, the cardiovascular system and the need of analgesics easing the time in the post anesthesia care unit (PACU). METHODS: After approval by the local ethics committee and written informed consent, 100 patients undergoing a cholecystectomy or a struma resection, were given either physostigmin (n = 51) or saline 0.9 % (n = 49) in a randomized fashion. The study was conceived to block a possible isoflurane-N2O/O2 (opioid-based plus relaxant) induced central anticholinergic syndrome and to evaluate the effects on the cardiovascular system on vigilance and on postoperative analgesic demand. Following parameters were measured: systolic and diastolic blood pressure, heart rate, respiratory rate, and arterial blood gases. In addition, vigilance was determined and typical anticholinergic symptoms (disorientation, slurred speech, agitation, nausea, emesis, cardiac arrhythmia and muscle shivering) were determined 10, 20, 40 and 60 minutes following the intravenous injection of physostigmin. Also, the need for the postoperative analgesic pethidine was evaluated among the two groups. RESULTS: Except for a significant reduction in the need of analgesics, a reduced diastolic pressure and heart rate and a lower incidence of muscle shivering there was no difference among the two groups. One major side effect following the use of physostigmin was the higher incidence of nausea in the im mediate minutes following injection. This effect may be due to the rapid injection of the anticholinergic compound. Otherwise there were no detrimental effects of physostigmin in patients. CONCLUSION: From the results it can be concluded that routine administration of an anticholinergic agent results in a short term beneficial effect in regard to vigilance, a lesser incidence of muscle shivering and a lesser demand for analgesics. However, because of the low incidence of a classical central anticholinergic syndrome, routine physostigmine is only indicated when agitation is diagnosed.

Adult↗

Production of procalcitonin (PCT) in non-thyroidal tissue after LPS injection.

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT, among other calcitonin precursors, is elevated in the serum of many conditions associated with a systemic inflammatory response syndrome, even in the absence of the thyroid gland. The aim of our study was to identify PCT-producing extrathyroidal tissues in primate sepsis. In order to induce PCT production, we treated four olive baboons ( papio cynocephalus anubis) with the endotoxin lipopolysaccharide (LPS) from s. typhimurium. We found an increase in serum PCT 3 to 5 hours after LPS injection to levels of 0.2 ng/ml, attaining a peak above 4 ng/ml PCT at 10 hours. In contrast, the untreated baboon had no detectable circulating PCT in the serum. In one animal, additional LPS boosting after 24 hours did not increase serum PCT further. Soluble proteins were extracted from different organs, fractionated by C18 extraction, and PCT was measured in an immunoluminometric assay (ILMA), which was specifically developed for this study. PCT concentrations above 0.2 ng/g of wet tissue were found in a variety of organs in LPS treated baboons, but not in the control baboon. Organs and tissues with the highest PCT concentration included liver, kidney, aorta, fat, ovaries, bladder and adrenal gland. RT-PCR confirmed an extrathyroidal origin of PCT. Importantly, CT-mRNA expression was found in liver, lung, kidney, adrenal, colon, skin, spleen, brain and pancreas. In conclusion, our data confirm previous findings in hamsters, indicating an extrathyroidal origin for PCT in sepsis. Our primate model offers a valuable tool for further investigation of PCT's pathophysiological role and its immunoneutralization as a therapy for sepsis.

Animals↗