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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 73 records · Page 4Linked to original sources

Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function.

The metyrapone test is used to test the hypothalamic-pituitary-adrenocortical axis. The present study aims to assess the diagnostic accuracy of combined stimulation of ACTH and compound-S (CMP-S). In addition, we analyzed the safety and practicability of this test as an outpatient procedure. A total of 327 metyrapone tests were analyzed retrospectively in 185 patients (mean age, 50.3 +/- 15.2 yr). One hundred thirteen patients had one test, and 72 patients had between 2 and 6 tests over 1-3 yr. Most patients suffered from pituitary adenomas (60 macroadenomas, 63 microadenomas) or other pituitary lesions (n = 29). Metyrapone (2 g) was given at 2400 h as an outpatient procedure. Blood samples for analysis of ACTH, CMP-S, and cortisol were taken at 0730 h. Stimulation of adrenal CMP-S and cortisol by pituitary ACTH demonstrated a dose-response curve with the shape of half a geometric parabola. CMP-S reached a plateau when ACTH rose above 175 ng/liter [r = 0.661, P < 0.0001 for ACTH <175 ng/liter; r = 0.083, P = not significant (NS) for ACTH >175 ng/liter], cortisol flattened at ACTH levels above 230 ng/liter (r = 0.633; P < 0.0001 for ACTH < 230 ng/liter; P = NS for ACTH >230 ng/liter). Alternatively, the sum of CMP-S plus cortisol also flattened when ACTH rose above 230 ng/liter (r = 0.696; P < 0.0001 for ACTH <230; P = NS for ACTH > 230 ng/liter). Receiver operating curve analysis defining a cut-off for ACTH at 150 ng/liter demonstrated a sensitivity of 47% and 67% at a cut-off level for CMP-S at 200 or 260 nmol/liter, respectively. The respective specificity was 82% and 68% for CMP-S. This compared with a sensitivity of 71% and specificity of 69% if the sum of CMP-S plus cortisol of 450 nmol/liter were used as cut-off. The response curve between CMP-S and ACTH implies a maximally stimulated adrenal cortex at circulating ACTH levels above 175 ng/liter. Single measurement of CMP-S using the cut-off at 200 nmol/liter, as suggested in the literature, yields a poor sensitivity of only 47% compared with ACTH. Despite the relatively high cross-reactivity of CMP-S in the cortisol assay, the sum of CMP-S and cortisol levels with a cut-off value of 450 nmol/liter yields a better diagnostic accuracy compared with CMP-S alone.

Adrenocorticotropic Hormone↗

2D simulation of transport and degradation in the River Rhine.

A simple 2D model has been developed for the simulation of mass transport and degradation of substances in the river Rhine. The model describes mass transport in the flow direction with a convective and a dispersive term. Transversal transport is described by segmenting the river and formulating a transversal exchange coefficient between the segments. Degradation can be formulated with any kinetics from first order to complex enzyme kinetics. The model was verified with monitoring data from the river Rhine. The hydrodynamic parameters such as dispersion coefficients and exchange coefficients were fitted to the conductivity, which was assumed to be non-degradable. The degradation term was fitted to ammonia values. The model was used to simulate measured concentrations of a readily (Aniline) and a poorly biodegradable substance (1,4-Dioxan) 10 m from the left river bank. It was the objective of this research program to develop a model which allows a realistic estimation of the locally and regionally predicted environmental concentration of chemical substances in the EU risk assessment scheme.

Ammonia↗

[Calculating the basal metabolic rate and severe and morbid obesity].

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the currently available predictive equations for basal metabolic rate (BMR) in subjects with obesity class II and III, and to assess the contribution by the components of a two-compartment model of body composition, namely the lean body mass (LBM) and the fat mass (FM) to the prediction. A second objective was to examine the reliability of the Harris Benedict equation in obese subjects, especially with a weight > or = 120 kg. PATIENTS AND METHODS: In 43 patients (age range 18 to 61 years, 5 men, 38 women) with obesity class II and III (body mass index, BMI, mean +/- SD 45.6 kg/m2 +/- 5.4 kg/m2, range 37.1-58.6 kg/m2) basal metabolic rate BMR was determined using indirect calorimetry (Deltatrac MBM, Datex, Instrumentarium Corp., Helsinki, Finnland) and the components of body composition were determined using the bioelectrical-impedance-analysis (BIA) method (BIA, Akern-Gerät, RJL Systems, Detroit). Calculated BMR was compared with measured BMR. RESULTS: The best fitting equations for predicting BMR in these 43 severe und morbidly obese subjects were the Harris-Benedict (ratio calculated BMR to measured, BMR mean +/- SD%; correlation coefficient r = 101 +/- 12.9; 0.69), the Jensen (101.5 +/- 12.3; 0.74), the Nelson (99.3 +/- 11.4; 0.76) and the Cunningham equation (98.9 +/- 11.7; 0.74). The predictive value of the original Harris-Benedict equation was slightly different from modified Harris-Benedict equation, which was recalculated by Roza et al. (101.1 +/- 12.9; 0.69 vs. 99.7 +/- 12.8; 0.69). In the group of the 22 subjects with a body weight > or = 120 kg ratio of estimated values for BMR using original Harris-Benedict equation to measured BMR was 102.2 +/- 15.4% (mean +/- SD%, r = 0.61), respectively 93.2 +/- 14.5% (r = 0.50) when weight was set at 120 kg due to current recommendations. The ratio calculated BMR/measured BMR according to the Nelson equation in this subgroup was 101.0 (12.1/0.74). CONCLUSION: In patients with obesity class II and III the equation of Harris-Benedict predicted the average BMR with acceptable precision for clinical use and was better fitting than most of the currently available predictive equations for basal metabolic rate (BMR). However, the recalculated version (by Roza et al.) was more accurate and should therefore be used instead of the original equation: BMR (men) = 88.362 + 4.799 x (length) + 13.397 x (weight) - 5.677 x (age); BMR (women) = 447.593 + 3.098 x (length) + 9.247 x (weight) - 4.330 x (age). The Nelson equation, including not only LBM but FM as additional predictor, was the best predicting equation ([108 LBM + 16.9 FM]0.239). Harris-Benedict equation had sufficient precision also in extreme obese subjects with a body weight > or = 120 kg, so there is no need for adaptation.

Adolescent↗

Procalcitonin: how a hormone became a marker and mediator of sepsis.

Calcitonin was discovered in the early 1960s [1], at which time it was assumed to be a single hormone with a yet-to-be-determined role in human physiology. Since then it has been found to be only one entity among a large array of related circulating peptides, at least one of which has a pivotal role in the host response to microbial infections [2, 3]. The aim of this review is to describe this metamorphosis of an endocrine hormone to a new class of hormokine mediators in infectious diseases.

Biomarkers↗

Graves' ophthalmopathy: natural history and treatment outcomes.

BACKGROUND: The pathogenesis of Graves' ophthalmopathy has not been yet clarified, and from a therapeutic standpoint Graves' ophthalmopathy remains an enigma. The natural course and effects of different treatment regimens are poorly documented. RESULTS: The mean observation period was 3.23 years (1-8.9 years) for all 196 patients, and 2.85 years (1-8.9 years) for the 81 patients with Graves' ophthalmopathy. The gender distribution was 77% female and 23% male in patients with Graves' disease and ophthalmopathy, and 81% female and 19% male in those patients without ophthalmopathy (p = 0.57). Seventy per cent of the patients developed Graves' ophthalmopathy within 12 months before or after the onset of the hyperthyroidism. Among the 81 patients with ophthalmopathy 53 (65%) received no therapy or only local protective agents. Twenty-five of these patients improved substantially, 26 did not change, and 2 deteriorated progressively. These results were independent of the severity of the EO (p = 0.42). Among the 11 patients initially treated with systemic corticosteroids 7 improved, 3 did not change, and 1 worsened. Five patients received initially orbital irradiation. Three improved and 2 did not change after radiotherapy. Orbital decompression was performed in 3 patients. Nine patients received a combination treatment. CONCLUSION: In conclusion, our study of a relatively large patient sample revealed the known epidemiological facts regarding Graves' disease and endocrine ophthalmopathy. The majority of patients needed no therapy or only local protective agents, and 47% improved spontaneously. Systemic corticosteroids and orbital irradiation appear to be equally effective as initial treatment in patients with more severe forms of Graves' ophthalmopathy.

Adult↗

Brinker requires two corepressors for maximal and versatile repression in Dpp signalling.

decapentaplegic (dpp) encodes a Drosophila transforming growth factor-beta homologue that functions as a morphogen in the developing embryo and in adult appendage formation. In the wing imaginal disc, a Dpp gradient governs patterning along the anteroposterior axis by inducing regional expression of diverse genes in a concentration-dependent manner. Recent studies show that responses to graded Dpp activity also require an input from a complementary and opposing gradient of Brinker (Brk), a transcriptional repressor protein encoded by a Dpp target gene. Here we show that Brk harbours a functional and transferable repression domain, through which it recruits the corepressors Groucho and CtBP. By analysing transcriptional outcomes arising from the genetic removal of these corepressors, and by ectopically expressing Brk variants in the embryo, we demonstrate that these corepressors are alternatively used by Brk for repressing some Dpp-responsive genes, whereas for repressing other distinct target genes they are not required. Our results show that Brk utilizes multiple means to repress its endogenous target genes, allowing repression of a multitude of complex Dpp target promoters.

Alcohol Oxidoreductases↗

Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein.

U7 snRNPs were isolated from HeLa cells by biochemical fractionation, followed by affinity purification with a biotinylated oligonucleotide complementary to U7 snRNA. Purified U7 snRNPs lack the Sm proteins D1 and D2, but contain additional polypeptides of 14, 50 and 70 kDa. Microsequencing identified the 14 kDa polypeptide as a new Sm-like protein related to Sm D1 and D3. Like U7 snRNA, this protein, named Lsm10, is enriched in Cajal bodies of the cell nucleus. Its incorporation into U7 snRNPs is largely dictated by the special Sm binding site of U7 snRNA. This novel type of Sm complex, composed of both conventional Sm proteins and the Sm-like Lsm10, is most likely to be important for U7 snRNP function and subcellular localization.

Amino Acid Sequence↗

Conditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-duration.

Measures of selective attention processing like latent inhibition (LI) and conditioned blocking (CB) are disturbed in some patients with schizophrenia. [LI is the delay in learning about the associations of a stimulus that has been associated with no event (versus de novo learning); CB is the delay in learning the associations of a stimulus-component when the other component has already started to acquire these associations.] We proposed: (1) to replicate the reported decreases of CB in patients without paranoid-hallucinatory symptoms; (2) to see if CB depends on the age of illness-onset and its duration, as reported for LI. We studied 101 young and old, acute and chronically ill patients with schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and compared them with 62 healthy controls matched for age, education and socio-economic background. CB was more evident in patients with a diagnosis of paranoid schizophrenia than other subtypes. An unusual persistence of high CB scores through testing was associated with productive symptoms (including positive thought disorder). Reduced CB related to the expression of (a) Schneider's first rank symptoms of ideas-of-reference and (b) to negative symptoms like poor rapport and poor attention. CB was less evident in the older patients and those with an earlier illness-onset. In contrast to the similar LI test of selective attention, CB is found in patients with paranoid schizophrenia and its expression is not related closely to illness duration. This implies that the two tests reflect the activity of different underlying processes. We suggest that reduced CB on initial test-trials in nonparanoid schizophrenia reflects the unusual persistence of controlled information processing strategies that would normally become automatic during conditioning. In contrast, continued CB during testing reflects an unusual persistence of automatic processing strategies.

Acute Disease↗

Macroprolactinaemia, the major unknown in the differential diagnosis of hyperprolactinaemia.

We report on 10 cases of macroprolactinaemia and discuss recent evidence that many patients with hyperprolactinaemia (8-26%, depending on the population studied) have in fact normal amounts of circulating prolactin but false-high values in commercial assays. This is caused by macromolecular prolactin (also named big-big prolactin or macroprolactin), a complex of prolactin with IgG antibodies leading to apparent hyperprolactinaemia. In spite of the expanding literature on this topic, it remains an underrecognised problem, typically causing unnecessary procedures such as laboratory controls, MRI of the pituitary, treatment with dopamine agonists or even pituitary surgery. Physicians involved with diagnosis and treatment of hyperprolactinaemia (general practitioners, gynaecologists, neurosurgeons, endocrinologists and biochemists) should suspect the presence of apparent hyperprolactinaemia in any patient with a high prolactin value but no related symptoms. Medical laboratories should be aware that their prolactin assay can interfere with macroprolactin and should implement the use of the PEG precipitation test in the work-up of hyperprolactinaemia, a simple and effective means of correctly diagnosing apparent hyperprolactinaemia.

Adolescent↗

A method to obtain right-side-out and sealed plasma membrane vesicles from the filamentous fungus Penicillium simplicissimum.

Plasma membrane vesicles were purified from the citrate excreting filamentous fungus Penicillium simplicissimum. The hyphae were disrupted by grinding in a glass bead mill and plasma membranes were obtained from a crude membrane fraction by partitioning in an aqueous dextran/polyethylene glycol two-phase system. The resulting enriched plasma membrane fraction contained only minor contaminations of marker enzymes of intracellular membranes, consisted of more than 90% of right-side-out vesicles and was sealed for potassium.

Cell Fractionation↗

[Surgical treatment of femoral neck pseudarthrosis associated with delayed union of ipsilateral femoral shaft fracture].

A femoral neck fracture combined with an ipsilateral shaft fracture is often primarily not diagnosed. The later treatment is technically more difficult, because in the choice of operative technique for the shaft fracture the neck fracture it was not considered. In this case report the treatment of the shaft fracture with a reamed nail, and the secondary stabilisation of the femoral neck fracture with screws resulted in a pseudarthrosis of the femoral neck with an unfavourable inclination of the fracture plane. Both fractures healed without complications after changing the nail against a bridging plate and an intertrochanteric osteotomy with correction in two planes.

Adult↗

World Stress Map of the Earth: a key to tectonic processes and technological applications.

Modern civilisation explores and penetrates the interior of the Earth's crust, recovers from it and stores into it solids, fluids and gases to a hitherto unprecedented degree. Management of underground structures such as boreholes or reservoirs take into account the existing stress either to take advantage of it or at least to minimise the effects of man-made stress. This paper presents the World Map of Tectonic Stresses (in short: World Stress Map or WSM) as a fundamental geophysical data-base. The impact of the WSM is pointed out: in the context of global tectonics, in seismic hazard quantification and in a wide range of technological problems in industrial applications such as oil reservoir management and stability of underground openings (tunnels, boreholes and waste disposal sites).

Earth, Planet↗

Knee laxity after ACL reconstruction with a BPTB graft.

UNLABELLED: The objective of the study was to compare prospectively short-term and mid-term results after ACL reconstruction with special focus on changes in instrumented knee laxity. METHODS: The original study group included prospectively 58 patients who underwent arthroscopically assisted ACL reconstruction with BPTB graft in a two-tunnel technique between 1991 and 1993. Seven patients were lost to follow-up, leaving 51 patients for a first follow-up at 6 months and a second follow-up at 3-6 years (mean 4.3 years). Clinical results were evaluated by means of the Lysholm score and the IKDC score. Laxity was assessed using a KT-1000 arthrometer applying an 89 N anterior load in 20 degrees of flexion. Increased laxity was defined as a 3 mm increase in AP translation between the first and the second follow-up. RESULTS: At mid-term follow-up pivot shift was negative in 86% of cases. IKDC score: normal = 28%, nearly normal = 44%, abnormal = 24%, severely abnormal = 4%. KT-1000: < 3 mm = 68%, 3-5 mm = 24%, > 5 mm = 8%. The mean KT-1000 side-to-side difference was 1.08 (0.17) mm at 6 months and 2.01 (0.29) mm at 3-6 years. The difference was statistically significant (P < 0.005). According to the defined criteria, seven patients had increased laxity at the second follow-up, suggesting a malfunction of the graft due to stretch-out or injury. In this subgroup the mean KT-1000 measurements were 0.86 (0.26) mm at the first follow-up and 5.93 (0.54) mm at the second follow-up. In five of these patients, a malposition of the tunnels was identified as a possible cause. In the remaining group, KT-1000 measurements did not differ significantly between the first and the second follow-up [1.12 (0.20) mm versus 1.37 (0.21) mm]. CONCLUSIONS: Increase in AP laxity occurred in 14% of our cases between the first and the second follow-up. In most of these cases increased laxity was due to inadequate surgical technique, especially malposition of bony tunnels. If tunnel position was correct, there was no evidence for elongation of grafts over time as a general principle.

Adult↗

Interfacing a silicon chip to pairs of snail neurons connected by electrical synapses.

Future hybrid neuron-semiconductor chips will consist of complex neural networks that are directly interfaced to electronic integrated circuits. They will help us to understand the dynamics of neuronal networks and may lead to novel computational facilities. Here we report on an elementary step towards such neurochips. We designed and fabricated a silicon chip for multiple two-way interfacing, and cultured on it pairs of neurons from the pedal ganglia of the snail Lymnaea stagnalis. These neurons were joined to each other by an electrical synapse, and to the chip by a capacitive stimulator and a recording transistor. We obtained a set of neuroelectronic units with sequential and parallel signal transmission through the neuron-silicon interface and the synapse, with a bidirectionally interfaced neuron-pair and with a signal path from the chip through a synaptically connected neuron pair back to the chip. The prospects for assembling more involved hybrid networks on the basis of these neuroelectronic units are considered.

Animals↗

Long-term outcome and prognosis of obsessive-compulsive disorder with onset in childhood or adolescence.

The aim of the catch-up follow-up study is to describe the long-term outcome of obsessive-compulsive disorder (OCD) with onset in childhood and adolescence. The psychiatric morbidity in adulthood including personality disorders was assessed and predictors in childhood for the course of obsessive-compulsive symptoms were examined. The total study group consisted of the entire patient population treated for OCD at our departments for child and adolescent psychiatry between 1980 and 1991. We reassessed 55 patients personally by way of structured interviews. The mean age of onset of OCD was 12.5 years and the mean follow-up time was 11.2 years. At the follow-up investigation 71% of the patients met the criteria for some form of psychiatric disorder, while 36% were still suffering from OCD. Of the patients with a present diagnosis of OCD 70% had at least one further clinical disorder (especially anxiety and affective disorders). The most frequent personality disorders diagnosed were obsessive-compulsive (25.5%), avoidant (21.8%), and paranoid (12.7%) personality disorders. In-patient treatment, terminating treatment against advice and tics in childhood or adolescence significantly correlated with more severe OC symptoms in adulthood.

Adolescent↗