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Beat Müller

Publications and source records attributed to Beat Müller.

At least 37 records · Page 2Linked to original sources
PubMed2005

Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study.

INTRODUCTION: Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores. METHOD: We evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 age-matched healthy control individuals. The patients had initially been enrolled in a prospective observational study investigating the prognostic value of endocrine dysfunction in critically ill patients ("PEDCRIP" Study). The prognostic value of MR-proADM levels was compared with those of two physiological scores and of various biomarkers (for example C-reactive Protein, IL-6, procalcitonin). MR-proADM was measured in EDTA plasma from all patients using a new sandwich immunoassay. RESULTS: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 48 had systemic inflammatory response syndrome. Median MR-proADM levels on admission (nmol/l [range]) were 1.1 (0.3-3.7) in patients with systemic inflammatory response syndrome, 1.8 (0.4-5.8) in those with sepsis, 2.3 (1.0-17.6) in those with severe sepsis and 4.5 (0.9-21) in patients with septic shock. In healthy control individuals the median MR-proADM was 0.4 (0.21-0.97). On admission, circulating MR-proADM levels in patients with sepsis, severe sepsis, or septic shock were significantly higher in nonsurvivors (8.5 [0.8-21.0]; P < 0.001) than in survivors (1.7 [0.4-17.6]). In a receiver operating curve analysis of survival of patients with sepsis, the area under the curve (AUC) for MR-proADM was 0.81, which was similar to the AUCs for IL-6, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II. The prognostic value of MR-proADM was independent of the sepsis classification system used. CONCLUSION: MR-proADM may be helpful in individual risk assessment in septic patients.

APACHE↗
PubMed2005

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671].

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice.

Adult↗
PubMed2005

Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance.

BACKGROUND: It is controversial whether the polycystic ovary syndrome (PCOS) per se increases low-grade chronic inflammation and whether this relates to central fat excess. In addition, the association between circulating sex hormones and body fat distribution in premenopausal women is debated. METHODS: Blood was drawn from 20 patients with PCOS and compared with 15 controls, matched for body mass index and age. Regional fat distribution was assessed using dual x-ray absorptiometry. RESULTS: Compared with controls, patients with PCOS had a higher trunk to extremity fat ratio (T/E fat), were more insulin resistant (higher homeostasis model assessment of insulin resistance and lower SHBG concentrations), and had higher levels of highly sensitive C-reactive protein, TNF-alpha, procalcitonin, and white blood cell count (all P < or = 0.04), even after adjusting for total body fat. However, additional adjusting for T/E fat eliminated or attenuated the effect of PCOS status on estimates of insulin resistance, on inflammatory mediators, and on white blood cell count but not on circulating sex hormones. Independently of each other, total body fat as well as T/E fat correlated with estimates of insulin resistance and most inflammatory mediators (P < or = 0.04). However, the correlations between T/E fat and circulating sex hormones (P < or = 0.02) were greatly reduced after adjustment for the presence of PCOS. CONCLUSION: The increase in low-grade chronic inflammation and in insulin resistance in women with PCOS is primarily associated with increased central fat excess rather than PCOS status per se. Procalcitonin represents a novel marker of the inflammatory activity of body fat and of PCOS.

Adipose Tissue↗
PubMed2005

Procalcitonin in bacterial infections--hype, hope, more or less?

An ideal marker for bacterial infections should allow an early diagnosis, inform about the course and prognosis of the disease and facilitate therapeutic decisions. Procalcitonin (ProCT) covers these features better as compared to other, more commonly used biomarkers, and thus, the current hype on ProCT has a solid scientific basis. A superior diagnostic accuracy of ProCT has been shown for a variety of infections, eg respiratory tract infections, meningitis, acute infectious endocarditis and pancreatitis. Importantly, a ProCT-based therapeutic strategy can safely and markedly reduce antibiotic usage in lower respiratory tract infections, the major cause of sepsis. Being a hormokine mediator, immunoneutralisation of ProCT might offer new hope for more effective treatment options in sepsis. It is now evidence-based that ProCT provides more information and, thereby, questions the currently used "gold standards" for the diagnosis of clinically relevant bacterial infections. Yet, ProCT is less than a perfect marker. ProCT can be increased in non-infectious conditions, and may remain low in infections. The diagnosis of bacterial infections will continue to require a critical clinical awareness, careful patient history, dedicated physical examination, and appropriate cultures. This review aims to help the clinician to understand the physiopathological basis, to appreciate strengths and weaknesses of this biomarker, and thereby to promote a rational implementation of ProCT in a routine setting.

Bacterial Infections↗
PubMed2005

Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test.

BACKGROUND/METHODS: Nighttime salivary cortisol (NSC) has been suggested to be a useful diagnostic test for Cushing's syndrome (CS). In the absence of published data on its day-to-day variability, we assessed the reproducibility of NSC by repeated measurements in healthy volunteers. Its diagnostic performance was compared with 24-h urinary free cortisol (UFC) and 1 mg overnight dexamethasone suppression test in 12 patients with CS, 20 healthy volunteers, 14 referred patients in which CS was excluded or not firmly established, 16 obese patients, and 20 women in late pregnancy. RESULTS: NSC showed a superior reproducibility in healthy volunteers with a low day-to-day variability as reflected by an intraclass correlation coefficient of 0.78. The receiver operating characteristic curve-estimated cutoff of 6.1 nmol/liter (0.22 microg/dl) demonstrated a sensitivity and specificity of 100% (area under the receiver operating characteristic curve, 1.0; 95% confidence interval, 0.94-1.0) in the diagnosis of CS. NSC, 24-h UFC [after adjusting the local laboratory cutoff to 504 nmol/d (183 microg/d)], and the urinary cortisol/creatinine ratio showed a tendency to be superior to 1 mg dexamethasone suppression test in correctly identifying CS. In late pregnancy, the preserved diurnal variation at a higher level of salivary cortisol reduced the specificity of NSC to 75%. CONCLUSION: Based on its remarkable reproducibility, easy noninvasive nature, and at least similar diagnostic performance, NSC appears to be a preferable alternative to 24-h UFC as a first-line screening test for CS. The cutoff values of NSC, 24-h UFC, and urinary cortisol/creatinine ratio have to be carefully adjusted using assay and center-specific reference ranges of sufficiently large populations.

Adult↗
PubMed2005

What are disease perceptions and subjective treatment goals of insulin treated diabetic patients?

BACKGROUND: Despite increasing importance of patient self-management, little is known about their own perceptions and treatment goals. OBJECTIVES: The aim of this explorative study was to examine what diabetic patients perceive as most concerning and what their own treatment goals are. METHODS: A 23-item anonymous questionnaire was distributed among type 1 diabetic patients treated with and without an insulin pump and insulin treated type 2 diabetic patients in the outpatient clinic of a University Hospital. 86% of the questionnaires were returned (n = 124). RESULTS: In open-ended questions, patients in all three groups together felt mostly restricted by their loss of freedom (24%), the dietary restrictions (17%) and the need to measure blood glucose (17%). Patients treated with an insulin pump worried more about hypoglycaemia and less about dietary restrictions. In closed-ended questions, patients were mostly concerned about hypoglycaemia and developing complications. However, the main treatment goal of both groups together was long-term good blood glucose control (63%). Further patient goals were the prevention of complications (27%) and the preservation of a good quality of life. Quality of life was a more important goal for type 1 diabetic patients (29%) than for type 2 diabetic patients (0%). Patients thought that blood glucose control was more important for their physicians (main treatment goal for 86%) than for themselves. CONCLUSION: Insulin treated patients with diabetes spontaneously express concerns about their actual quality of life and daily hassles and mention long-term worries after explicit questioning. For their main treatment goals they choose mainly long-term goals. According to the patients, physicians tend to overestimate blood glucose control.

Adult↗
PubMed2005

Phosphorus retention in small constructed wetlands treating agricultural drainage water.

The construction of artificial wetlands has become a measure increasingly applied to reduce nonpoint-source (NPS) pollution and to contribute to the restoration of eutrophic lakes and coastal waters. In a 2-yr study monitoring fluxes of particulate and dissolved phosphorus (P) in a small artificial wetland for the treatment of agricultural drainage water in Central Switzerland, water residence time was identified as the main factor controlling P retention in the system. Since most of the annual P load (62% as dissolved reactive phosphorus, DRP) was related to high discharge events, it was not average but minimum water residence time during flood events that determined the wetland's P retention. In agreement with a continuous stirred tank reactor (CSTR) model, our investigations suggest a minimum water residence time of 7 d to retain at least 50% of the bioavailable P. The investigated wetland retained only 2% of the bioavailable P, since the water residence time was shorter than 7 d during 61% of time in both years. Settling of phytoplankton rather than DRP uptake into phytoplankton limited the retention of bioavailable P. The overall retention efficiency of 23% total phosphorus (TP), corresponding to a surface related retention of 1.1 g P m(-2) yr(-1), was due to the efficient trapping of pedogenic particles.

Agriculture↗
PubMed2005

Cortisol response in relation to the severity of stress and illness.

BACKGROUND: The aim of the study was to compare the adrenal response, the course of the ACTH/cortisol ratio, as well as the variance and the diagnostic performance of different cutoffs after 1 and 250 microg ACTH stimulation in different stress situations. METHODS: We investigated three groups with increasing stress levels: ambulatory controls (group A; n = 20), hospitalized medical patients (group B; n = 25), and patients undergoing coronary artery bypass grafting (group C; n = 29). All subjects underwent four consecutive ACTH stimulation tests and were randomized to either a 1- or 250-microg dose. RESULTS: Stimulated cortisol levels in group A were similar to basal cortisol levels under maximal stress (C3; P = 0.8). Peak cortisol concentrations were higher after 250 microg compared with 1 microg ACTH in group B (P = 0.006) and under maximal stress after extubation (group C3; P = 0.027), whereas there were no differences in group A. The ACTH/cortisol ratio was lower in surgical patients after extubation compared with unstressed conditions (P < or = 0.03) The within-subject variance was similar in ambulatory controls and medical patients and after both ACTH doses (all 17-36% of total variance). Cutoff dependent, the diagnosis of relative adrenal insufficiency would have been made in 0-58.3%, respectively. CONCLUSION: In moderate and major stress situations, cortisol concentrations in patients without hypothalamic-pituitary-adrenal disease were higher after stimulation with 250 microg compared with 1 mug ACTH. Data from our study give insight into the physiological adaptations of the hypothalamic-pituitary-adrenal axis to stress.

Adaptation, Physiological↗
PubMed2005

Low-grade inflammation and estimates of insulin resistance during the menstrual cycle in lean and overweight women.

BACKGROUND: Inflammatory markers and insulin resistance are independent cardiovascular risk factors and are thought to be influenced by sex steroids. We investigated changes of inflammatory markers and estimates of insulin resistance during the menstrual cycle, their variances, and their relationship to each other, sex steroids, and regional body fat distribution. METHODS: Eight normal weight (body mass index, 21.6 +/- 1.9 kg/m(2)) and nine overweight (body mass index, 30 +/- 2.4 kg/m(2)) young women with normal ovarian function were assessed 15 times throughout the menstrual cycle. Regional fat distribution was assessed using dual x-ray absorptiometry. RESULTS: Concentrations of highly sensitive C-reactive protein (hs-CRP) changed significantly during the menstrual cycle and were highest in the early follicular phase (P < 0.00001). SHBG concentrations were stable in the follicular phase but increased in the luteal phase (P < 0.00001). During the follicular phase, estimates of insulin resistance had a higher within-subject variance when determined by the homeostasis model assessment index (42%) than when estimated by SHBG concentrations (5%, P < 0.05). During the menstrual cycle, using repeated measurements, hs-CRP correlated inversely to estradiol (beta-coefficient, -0.23, P < 0.0001) and SHBG concentrations (beta-coefficient, -0.83, P = 0.004). Central accumulation of body fat correlated to the mean hs-CRP concentration (r = 0.63, P = 0.007) and the mean homeostasis model assessment index for insulin resistance (r = 0.75, P = 0.001). CONCLUSION: We demonstrate that serum concentrations of hs-CRP and SHBG significantly change during the menstrual cycle. We reveal a close link between sex steroids, subclinical inflammation, insulin resistance, and body fat distribution in regularly menstruating women.

Absorptiometry, Photon↗
PubMed2005

Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue.

Human adipose tissue is a contributor to inflammation- and sepsis-induced elevation of serum procalcitonin (ProCT). Several calcitonin (CT) peptides, including ProCT, CT gene-related peptide (CGRP), and adrenomedullin (ADM) are suspected mediators in human inflammatory diseases. Therefore, we aimed to explore the expression, interactions, and potential roles of adipocyte-derived CT peptide production. Expression of CT peptide-specific transcripts was analyzed by RT-PCR and quantitative real-time PCR in human adipose tissue biopsies and three different inflammation-challenged human adipocyte models. ProCT, CGRP, and ADM secretions were assessed by immunological methods. Adipocyte transcriptional activity, glycerol release, and insulin-mediated glucose transport were studied after exogenous CGRP and ADM exposure. With the exception of amylin, CT peptides were expressed in adipose tissue biopsies from septic patients, inflammation-activated mature explanted adipocytes, and macrophage-activated preadipocyte-derived adipocytes. ProCT and CGRP productions were significantly augmented in IL-1beta and lipopolysaccharide-challenged mesenchymal stem cell-derived adipocytes but not in undifferentiated mesenchymal stem cells. In contrast, ADM expression occurred before and after adipogenic differentiation. Interferon-gamma coadministration inhibited IL-1beta-mediated ProCT and CGRP secretion by 78 and 34%, respectively but augmented IL-1beta-mediated ADM secretion by 50%. Exogenous CGRP and ADM administration induced CT, CGRP I, and CGRP II mRNAs and dose-dependently (10(-10) and 10(-6) m) enhanced glycerol release. In contrast, no CGRP- and ADM-mediated effects were noted on ADM, TNFalpha, and IL-1beta mRNA abundances. In summary, CGRP and ADM are two differentially regulated novel adipose tissue secretion factors exerting autocrine/paracrine roles. Their lipolytic effect (glycerol release) suggests a metabolic role in adipocytes during inflammation.

Adipocytes↗
PubMed2005

Radical cations of phenyl-substituted aziridines: what are the conditions for ring opening?

Radical cations were generated from different phenyl-substituted aziridines by pulse radiolysis in aqueous solution containing TlOH.+, N3. or SO4.- as oxidants or in n-butyl chloride, by 60Co gamma radiolysis in Freon matrices at 77 K, and in some cases by flash photolysis in aqueous solution. Depending on the substitution pattern of the aziridines, two different types of radical cations are formed: if the N atom carries a phenyl ring, the aziridine appears to retain its structure after oxidation and the resulting radical cation shows an intense band at 440-480 nm, similar to that of the radical cation of dimethylaniline. Conversely, if the N atom carries an alkyl substituent while a phenyl ring is attached to a C-atom of the aziridine, oxidation results in spontaneous ring opening to yield azomethine ylide radical cations which have broad absorptions in the 500-800 nm range. In aqueous solution the two types of radical cations are quenched by O2 with different rates, whereas in n-butyl chloride, the ring-closed aziridine radical cations are not quenchable by O2. The results of quantum chemical calculations confirm the assignment of these species and allow to rationalize the different effects that phenyl rings have if they are attached in different positions of aziridines. In the pulse radiolysis experiments in aqueous solution, the primary oxidants can also be observed, whereas in n-butyl chloride a transient at 325 nm remains unidentified. In the laser flash experiments, both types of radical cations were also observed.

Aziridines↗
PubMed2005

What cardiologists do need to know about procalcitonin.

This review will highlight the potential application of procalcitonin, a novel marker of systemic bacterial infection, in two clinical settings relevant to cardiologists: infective endocarditis (IE) and lower respiratory tract infections (LRTI): The variability in the clinical presentation of infective endocarditis (IE) makes the diagnosis a clinical challenge. However, rapid diagnosis and initiation of effective treatment are essential to good patient outcome. Serum calcitonin precursor levels, including procalcitonin, are elevated in systemic bacterial infections and seem to be helpful in the diagnosis of IE. The utility of procalcitonin in clinical practice was examined in a prospective cohort of patients with the suspicion of IE. Procalcitonin was significantly higher in patients with IE (median 6.56 microg/L) as compared with patients with other final diagnoses (median 0.44 microg/L, p < 0.001). The area under the ROC curve using procalcitonin to predict infective endocarditis was 0.856, as compared to 0.657 for C-reactive protein. The optimum concentration of procalcitonin for the calculation of positive and negative predictive accuracy as obtained from the ROC curve was 2.3 microg/L. Using this cut-off, the test characteristics of procalcitonin were as follows: sensitivity 81%, specificity 85%, negative predictive value 92%, positive predictive value 72%. Although most LRTIs are due to viral infections, they are very often treated with antibiotics. This excessive use of antibiotics is believed to be the main cause of the spread of antibiotic-resistant bacteria. A procalcitonin-based therapeutic strategy has shown to reduce antibiotic usage in LRTI. Based upon serum procalcitonin levels, the use of antibiotics was more or less discouraged (<0.1 or <0.25 microg/L) or encouraged (> or =0.5 or > or =0.25 microg/L), respectively. Final diagnoses included pneumonia (36%), acute exacerbation of COPD (25%), and acute bronchitis (24%). Clinical and laboratory outcome was similar in both groups and favourable in 96.7%. In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (p < 0.001), as compared to the standard group. Thus, using a sensitive assay, procalcitonin-guidance substantially and safely reduced antibiotic usage in LRTI.

Anti-Bacterial Agents↗
PubMed2005

Serum estradiol after single dose hCG administration correlates with Leydig cell reserve in hypogonadal men: reassessment of the hCG stimulation test.

The hCG stimulation test with assessment of serum testosterone (T) is used for evaluation of testicular function. This retrospective study was undertaken to estimate the diagnostic value of stimulated estradiol (E2) levels in the assessment of Leydig cell function. Serum T and E2 before and after repeated daily hCG injections in 23 adult men with clinically suspected or established primary hypogonadism were studied. After hCG administration serum T increased gradually with peak levels after 72 hours (delta84%, p=0.003). In contrast, serum E2 concentrations reached their maximal levels 24 hours after the first injection (delta168%, p=0.001). Serum T and E2 responses were more attenuated in men with LH > or =17 IU/L as compared to men with lower LH levels. Peak E2 levels after 24 hours correlated significantly with peak T levels after 3 days. We conclude that the increase in serum E2 levels 24 hours after a single hCG injection is an useful additional measure of Leydig cell function. Assessment of E2 increments would render the test procedure more practical, less time-consuming and more cost-effective than assessing peak T levels after 72 hours.

Adult↗
PubMed2004

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study.

INTRODUCTION: Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores. METHODS: Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay. RESULTS: On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20-2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100-2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in non-surviving [corrected] than in surviving [corrected] sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score. CONCLUSION: Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results.

APACHE↗