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Biomedical subjects

M J Müller

Publications and source records attributed to M J Müller.

At least 19 recordsLinked to original sources
PubMed1998

Hepatic energy and substrate metabolism: a possible metabolic basis for early nutritional support in cirrhotic patients.

In the liver, the in vivo assessment of metabolic functions is limited by methodologic problems. The present evidence suggests that the liver contributes to 20-30% of whole body energy expenditure. Hepatic fuel selection can change considerably under different circumstances. During tissue catabolism (i.e., depletion of glycogen stores, increased lipid oxidation), the "hepatic respiratory quotient (RQ)" is lower than whole body RQ, suggesting that hepatic catabolism exceeds whole body catabolism. By contrast, the hepatic RQ may exceed whole body RQ during tissue anabolism (i.e., after full repletion of hepatic glycogen stores and significant lipogenesis). In cirrhosis, both the hepatic RQ and the whole body RQ are markedly reduced. When compared with the whole body level, the cirrhosis-induced decrease in the hepatic RQ is more pronounced. Given that liver catabolism exceeds (or possibly precedes) whole body catabolism, early nutritional support is mandatory in cirrhotic patients. The assessment of hepatic, in addition to whole body, energy metabolism may provide a basis for future recommendations of more specific nutritional support in patients with liver diseases.

Animals↗
PubMed1998

The symmetry of symptom patterns in pre-post treatment designs.

This article proposes a new nonparametric method for statistical evaluation of clinical pre-post treatment designs. In clinical research, models of marginal symmetry typically are estimated from log-linear models of axial and quasi-symmetry. As such, they provide overall goodness-of-fit information concerning change in probabilities of categories of one variable that was observed twice. This paper proposes the following three extensions: (1) using models of marginal symmetry for changes in patterns of two or more variables, and (2) following up global marginal symmetry tests using Lehmacher's sign tests. (3) To protect the experiment-wise alpha, a modified Bonferroni-Holm procedure is proposed. The new approach allows researchers to make statements about treatment effects at the level of single symptoms. Examples illustrate application of all three symmetry models and the follow-up test using data from pharmaco-psychiatry. The discussion relates Lehmacher's tests to two-sample Configural Frequency Analysis of multi-discrimination types. Strategies of statistical significance testing are presented and the importance of the proposed methodological approach for psychiatric research is discussed.

Humans↗
PubMed1998

Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome.

In a multicenter, double-blind, parallel group trial, the efficacy of risperidone (RIS) was compared with a combination of haloperidol and amitriptyline (HAL/AMI) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder, depressive type, a major depression with psychotic features, or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria. A total of 123 patients (62 RIS; 61 HAL/AMI) were included; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI. Efficacy results for those 98 patients (47 RIS; 51 HAL/AMI) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale (RIS 37%; HAL/AMI 51%) and the Bech-Rafaelsen Melancholia Scale total scores (RIS 51%; HAL/AMI 70%). The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group (p < 0.01), mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features, whereas treatment differences in the other diagnostic subgroups were not significant. The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS (37%) than under HAL/AMI (31%). Adverse events were reported by 66% of RIS and 75% of HAL/AMI patients. The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms. However, subgroup differences have to be considered.

Adolescent↗
PubMed1997

Identification of high- and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients.

The clinical relevance of malnutrition and hypermetabolism in end-stage liver disease, as well as their effects on survival after liver transplantation (LTx), are largely unknown. This study investigates the prognostic value of nutritional and metabolic parameters obtained before LTx for survival after LTx. One hundred fifty patients with end-stage liver disease undergoing LTx were assessed prospectively and followed for a mean period of 46 +/- 16 months after LTx. All patients were randomized into a study group and a validation group, each comprising 75 patients. Body composition analysis (24-hour urinary creatinine excretion, anthropometry, bioelectrical impedance analysis), deviation of measured from predicted resting energy expenditure (deltaREE), year of transplantation, and several variables known to be of prognostic relevance in patients with liver disease undergoing conservative treatment were analyzed. Kaplan-Meier and log rank analysis showed that hypermetabolic patients (deltaREE > +20%) and patients with a body cell mass (BCM) < 35% of body weight tended to have reduced survival after LTx. A risk profile on the basis of deltaREE and BCM identified patients with high risk (5-year survival rate, 54%) and low risk (5-year survival rate, 88%; P < .01). The predictive power of this risk profile was independent of the presence of ascites and clinical edema, and its validity was confirmed in the validation group (P < .01). The Child-Pugh score was not of prognostic value. We conclude that a poor nutritional state, as well as hypermetabolism, adversely affects survival after LTx. These potentially treatable presurgical factors deserve close attention in interventional studies.

Adult↗
PubMed1997

Use of positron emission tomography (PET) in the assessment of skeletal muscle glucose metabolism.

Non invasive imaging techniques, such as, positronemission tomography (PET), contribute to our present knowledge of glucose metabolism. Besides measurements of net glucose metabolism, PET provides insights into complex processes of intracellular glucose metabolism (i.e., glucose transport and phosphorylation) and is also capable to measure muscular blood flow as a possible determinant of glucose metabolism.

Diabetes Mellitus, Type 2↗
PubMed1997

Side effects of adjunct light therapy in patients with major depression.

Adjunct bright-light therapy has been suggested to augment antidepressant drug treatment in patients with non-seasonal major depression. Side effects of the combined therapy have not been investigated thus far. Therefore, somatic complaints and side effects of combined therapy were evaluated in 28 patients with major depression (DSM-III-R) randomly assigned to either trimipramine or trimipramine and serially applied adjunct bright-light therapy. Response rates were comparable in both treatment groups and rates of newly emergent side effects during treatment were generally low. The most prominent unfavourable side effects of adjunct bright-light therapy as compared with trimipramine monotherapy were aggravated sedation, persisting restlessness, emerging sleep disturbance and decreased appetite as well as the worsening of vertigo. Discriminant analysis revealed that the combination of trimipramine with bright light results in a different side effect profile compared with drug monotherapy.

Antidepressive Agents, Tricyclic↗
PubMed1997

Dietary underreporting: validity of dietary measurements of energy intake using a 7-day dietary record and a diet history in non-obese subjects.

Substantial dietary underreporting questions the validity of dietary measurements of energy intake (EI). The present study compares the value of a 7-day prospective dietary record (7dDR) with a computer program-based diet history (DH). 7dDR and DH were performed in 50 non-obese subjects (33 females, 17 males, mean age 26.1 years, BMI 18.9-29.6 kg/m2) using total energy expenditure (EE = sum of resting metabolic rate as measured by indirect calorimetry plus energy expenditure derived from an activity protocol) as standard for the validity of data on EI. EI was 2,206 (728-3,646) kcal/day for 7dDR and 2,398 (566-4,764) kcal/day for DH. There was an association between EI for 7dDR and EI for DH (r = 0.6, p < 0.0001). Underreporting [i.e. a difference between EI and EE (delta E = EI - EE)] of 20% or more was seen in 48% (7dDR, mean -1,047 kcal/day, range -616 to -1,895, or -38.8% of EE) or 48% (DH, -1,151 kcal/day, -594 to -2,057 kcal/day, or -42.3% of EE). Considerable differences were found between delta E for 7dDR and delta E for DH (mean 603, range 26-2,033 kcal/day), and only 34% of underreporting subjects were identified by both dietary measurements. It is concluded that at the individual level dietary underreporting is influenced by the dietary assessment tool.

Adult↗
PubMed1996

The creatinine approach to estimate skeletal muscle mass in patients with cirrhosis.

The creatinine-method to estimate muscle mass is frequently used in clinical studies, although the validity of this approach is uncertain in patients with cirrhosis. In this study 102 patients with cirrhosis differing in cause, clinical state, liver, and renal function were investigated to determine whether reduced liver or renal function may explain in part the low levels of urinary creatinine excretion frequently observed in these patients. Muscle mass assessed by 24-hour urinary creatinine excretion was compared with anthropometrically obtained muscle mass calculated from arm muscle area (AMA), and with body cell mass (BCM) estimated by bioelectrical impedance analysis and total body potassium counting. In cirrhosis, the 24-hour urinary creatinine excretion was 10.4% and AMA was 19% lower than predicted values. The differences between the results obtained by different methods did not show any relation to parameters of liver function (ICG-t1/2, caffeine-t1/2, MEGX-test, cholinesterase) or the severity of liver disease (i.e., Child-Pugh score). In contrast, renal function was strongly correlated with the differences between creatinine- and anthropometric-muscle mass (r = .64, P < .001). At the same time, patients with normal renal function (62% of the whole population) had significantly higher creatinine (29.1 +/- 8.5 vs. 15.8 +/- 6 kg, P < .001) and anthropometric-muscle mass (22.4 +/- 6 vs. 17.9 +/- 5.3 kg; P < .01) than patients with reduced renal function (38% of the patients). In addition, significantly higher differences between measured and predicted values of urinary creatinine excretion (-0.389 +/- 0.33 vs. 0.06 +/- 0.31 g/24 h; P < .001) and of AMA (13.2 +/- 12 vs. 7.2 +/- 12 cm2; P < .03) were found in the subgroup with impaired renal function. In conclusion, renal dysfunction but not reduced liver function systematically affects the urinary creatinine method for the estimation of skeletal muscle mass in cirrhosis.

Adult↗
PubMed1996

Metabolic, endocrine, haemodynamic and pulmonary responses to different types of exercise in individuals with normal or reduced liver function.

UNLABELLED: The liver is central to the metabolic response to exercise but measurements of effects of reduced liver function on the physiological adaptation to exercise are scarce. We investigated metabolic, endocrine, pulmonary and haemodynamic responses to exercise in 15 healthy untrained controls (Co) and in 30 subjects with reduced liver function (i.e. liver cirrhosis, Ci). The following protocols were used: protocol 1 maximal oxygen uptake (VO2max) and anaerobic threshold (AT), protocol 2 stepwise increases in exercise intensity from 0 to 40% VO2max giving steady-stage conditions, protocol 3 1 h exercise at 20% VO2max. Muscle glycogen content was determined in 15 Ci. Spirometry was essentially normal in Ci. RESULT: protocol 1 Ci had impaired VO2max and reduced AT (P < 0.05). Basal plasma concentrations of insulin, glucagon, growth hormone and adrenaline were increased in Ci (P < 0.05); cortisol was normal. During exercise, only glucagon remained different between groups. In protocol 2 Ci had decreased resting respiratory exchange ratio (RQ: p < 0.05) associated with increased plasma concentrations of free fatty acids and glycerol. They had disproportionately enhanced lipolysis and RQ. heart rate (+24%), ventilation (+28%), thermal effects of exercise (+31%) and intrapulmonary shunt volume (+76%), which accounted for 11.7 (SD 3.0) or 7.4 (SD 0.9%) of cardiac output during exercise in Ci and Co, respectively (P < 0.05 for all the differences reported). The metabolic effects of Ci were independent of the clinical and nutritional state of the patients. In protocol 3 muscle glycogen content was highly variable in Ci, but mean values were normal [16.9 (SD 8.9) mumol.g-1 wet mass]. Glycogen content positively correlated with resting and exercise-induced RQ, but negatively correlated with the exercise-induced alterations in plasma glucose concentration. From these results we concluded that with reduced liver function VO2max and AT are reduced, but metabolic, pulmonary and haemodynamic responses per unit power output are enhanced. Muscle glycogen content would seem to contribute to the metabolic response, but its mobilization to be limited in individuals with reduced liver function.

Adult↗
PubMed1996

Xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular reperfusion injury of the liver.

Although reactive oxygen metabolites may play a pivotal role in mediating microvascular reperfusion injury, the source of these radicals is still a matter of controversy. With the use of spectrophotometry and intravital microscopy we studied the role of xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular injury in rats. After 20 min of global hepatic ischemia and splanchnic vascular congestion, followed by 40 min of reperfusion (n = 8), xanthine oxidase activities in hepatic venous (26.9 +/- 4.7 nmol/ml x min) and systemic arterial blood (16.3 +/- 2.5 nmol/ml x min) were found significantly (p < .01) increased when compared with sham-operated controls (6.8 +/- 0.9 and 6.0 +/- 0.8 nmol/ml x min, n = 8). The increase of xanthine oxidase activity was accompanied by oxygen radical-mediated intravascular hemolysis. Intravital microscopy (n = 6) revealed accumulation of leukocytes within the postischemic hepatic microvasculature with stasis in sinusoids (75.9 +/- 8.9 per liver lobule) and adherence to the endothelial lining of postsinusoidal venules (534.7 +/- 125.3 per mm2 endothelial surface). Concomitantly, compromised microvascular reperfusion was characterized by perfusion deficits of individual sinusoids (25.6 +/- 4.0% nonperfused sinusoids). The xanthine oxidase inhibitor allopurinol (50 mg/kg b.wt., orally, n = 6) and the radical scavenger superoxide dismutase (60000 IU/kg b.wt., IV, n = 6) effectively (p < .01) inhibited both sinusoidal leukostasis (16.1 +/- 2.6 and 32.1 +/- 3.1 cells/lobule) and venular leukocyte adherence (247.6 +/- 7.9 and 205.0 +/- 38.0 cells/mm2), and, hence, reduced microcirculatory deteriorations, indicated by the attenuation of sinusoidal perfusion failure (2.8 +/- 0.8 and 9.0 +/- 3.1%). Our results support the hypothesis that portal triad crossclamping-induced microvascular reperfusion injury is triggered by superoxide radicals derived from the xanthine oxidase system.

Allopurinol↗
PubMed1996

Neuroendocrine effects of a 20-mg citalopram infusion in healthy males. A placebo-controlled evaluation of citalopram as 5-HT function probe.

Pharmacokinetic measurements, neuroendocrine responses, and side effects profiles of intravenous infusions of 20 mg citalopram over 30 minutes during the early afternoon have been studied. Eight healthy male volunteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound showed a double exponential decay. Demethyl and didemethyl metabolites were not detectable, but low concentrations of the propionic acid derivative of citalopram were found. Determination of the citalopram enantiomers yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine response to the drug was characterized by significant increases in plasma prolactin and cortisol. Except for one subject, who developed pronounced side effects, human growth hormone showed a surge following saline that was inhibited following citalopram. Rectal temperature and heart rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxytryptamine nerve terminals, the present data suggest that it might be a promising tool for the investigation of serotonergic function in the human brain in vivo.

Citalopram↗
PubMed1996

Weight gain and increased concentrations of receptor proteins for tumor necrosis factor after patients with symptomatic HIV infection received fortified nutrition support.

OBJECTIVE: To determine whether certain nutrients and dietary factors act as modulators of the immune system and improve the nutritional status of immunocompromised patients. DESIGN: Controlled, double-blind, crossover phase trials of the effects of a fortified formula in patients infected with the human immunodeficiency virus (HIV). Patients consumed a control formula for 4 months and a study formula for 4 months. SUBJECTS: Ten men with symptomatic HIV infection who were following stable medication regimens and had no malignancies, mycobacteriosis, or additional virus infection requiring systemic treatment. INTERVENTION: Formula fortified with alpha-linolenic acid (1.8 g/day), arginine (7.8 g/day), and RNA (0.75 g/day) and a standard formula. MAIN OUTCOME MEASURES: Nutritional status determined by anthropometric, bioelectrical, biochemical, and dietary assessment; energy expenditure determined by indirect calorimetry; disease progression; CD4 lymphocyte counts; HIV p24 antigen plasma concentrations; tumor necrosis factor (TNF) receptor proteins; and compliance control parameters. STATISTICAL ANALYSES PERFORMED: Student's t tests for paired and unpaired data. RESULTS: Fortified nutrition resulted in a weight gain (+ 2.9 kg/4 months vs -0.5 kg/4 months with the control formula, P < .05), an incorporation of eicosaenoic acid into erythrocyte cell membranes (+ 47% of baseline values, P < .05), and increased plasma arginine concentrations (96.8 +/- 45.1 vs 51.8 +/- 20.9 mumol/L, P < .01). The serum concentrations of the soluble tumor necrosis factor receptor (sTNFR) proteins increased during the study period (sTNFR 55 = + 0.23 vs -0.40 ng/mL, P < .001; sTNFR 75 = + 0.90 vs -0.36 ng/mL, P < .01), whereas no changes in CD4+ lymphocyte counts were observed. CONCLUSION: Increasing dietary intakes of n-3 polyunsaturated fatty acids, L-arginine, and RNA increased body weight, possibly by modulating the negative effects of TNF.

Adolescent↗