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Biomedical subjects

M Neuhäuser

Publications and source records attributed to M Neuhäuser.

At least 19 recordsLinked to original sources
PubMed2006

Muscle force and fatigue in patients with sepsis and multiorgan failure.

INTRODUCTION: Neuromuscular abnormalities are found frequently in sepsis and multiorgan failure (MOF). Surprisingly, however, there are no data on maximum skeletal muscle force and fatigue in these patients. OBJECTIVES: To test the research hypotheses that adductor pollicis (AP) force would be lower in patients with sepsis, whereas fatigue would not differ between patients and immobilized but not infected volunteers. DESIGN AND SETTING: Prospective study; university intensive care unit and laboratory. PATIENTS: Patients with sepsis and MOF (sequential organ failure assessment (SOFA) score >10) and healthy volunteers. INTERVENTIONS: Fatigue was evoked during 20[Symbol: see text]min of intermittent tetanic ulnar nerve stimulation achieving 50% of maximum AP muscle force. MEASUREMENTS AND RESULTS: We measured evoked AP muscle force and fatigue, and compound muscle action potential (CMAP), and performed standard electrophysiological tests in 13 patients, and in 7 volunteers before and after immobilization. Maximum force (20+/-16 vs 65+/-19N; p<0.01) and CMAP (3.6+/-2.5 vs 10+/-2.5 mV; p<0.05) were markedly decreased in patients; however, fatigue and ulnar nerve conduction velocity did not differ from volunteers, and a decrement of CMAP was not observed with nerve stimulation frequencies up to 40 Hz. All patients with critical illness polyneuropathy, and an additional 50% of those without, had significant muscle weakness. CONCLUSION: Peripheral muscle force is markedly decreased in sepsis, without evidence for an increased fatigability. Muscle weakness was most likely due to a sepsis-induced myopathy and/or axonal neuropathy, and was not the result of an immobilization atrophy.

Action Potentials↗
PubMed2006

Does perioperative administration of rofecoxib improve analgesia after spine, breast and orthopaedic surgery?

BACKGROUND AND OBJECTIVE: Data on the effectiveness of cyclooxygenase 2 inhibitors in postoperative pain therapy vary widely. We tested in a prospective, placebo-controlled, randomized, double-blind trial the hypotheses that perioperative (i.e. preoperative and postoperative) administration of the cyclooxygenase 2 inhibitor rofecoxib decreases pain scores and morphine consumption after spine, breast and orthopaedic surgery. METHODS: Five hundred and forty patients scheduled for spine, breast or orthopaedic surgery were randomly assigned to receive in combination with postoperative morphine via patient controlled analgesia pump for 4 days either rofecoxib 50 mg administered perioperatively, rofecoxib 50 mg administered only postoperatively, or placebo. Primary outcome criteria were pain score at rest (numeric rating scale 0-4) and morphine consumption. RESULTS: Perioperative rofecoxib significantly decreased pain score 0 (0-1) vs. 1 (0-2) (median (interquartile range)), and morphine consumption 18 (6-33) vs. 22.5 (12-38) compared with placebo. In contrast, rofecoxib when administered only postoperatively did not significantly improve analgesic effects or side-effects at time of assessment of the main criteria (24 h after skin closure), but during the follow-up period at 48 h and 72 h after skin closure pain scores and morphine consumption were improved compared to placebo. The analgesic effects of rofecoxib were independent from the type of surgery. CONCLUSIONS: Perioperative administration of the cyclooxygenase 2 inhibitor rofecoxib decreases pain scores and morphine consumption after orthopaedic, breast and spine surgery. However, the benefit of preoperative administration of the cyclooxygenase 2 inhibitor seems to be only moderate, suggesting that early postoperative administration may be a useful alternative approach. There is no evidence that the type of surgery influences analgesic effects of cyclooxygenase 2 inhibitors.

Adolescent↗
PubMed2006

Methacholine challenge tests: sample sizes required in crossover trials.

OBJECTIVE: Methacholine challenge testing is common for assessing the pharmacodynamic properties of anti-asthma drugs. In order to design studies and to interpret published studies, sample size calculations are essential. Unfortunately, wrong sample sizes were previously reported in the literature. We present correct sample sizes required for the comparison of two treatments based on methacholine challenge testing in a crossover study. METHODS AND RESULTS: Formulas for sample size calculations and the resulting number of subjects required for a specified power are presented for studies designed to show a difference as well as for equivalence and non-inferiority studies. CONCLUSIONS: A much larger sample size is required for methacholine challenge testing than previously reported.

Algorithms↗
PubMed2005

Age at diagnosis of isolated unilateral retinoblastoma does not distinguish patients with and without a constitutional RB1 gene mutation but is influenced by a parent-of-origin effect.

Patients with hereditary cancer are usually diagnosed earlier than patients with non-hereditary tumours. In children with isolated unilateral retinoblastoma, some of whom have a hereditary predisposition, this rule has been subject to debate. We have analysed the clinical manifestation of disease in 188 children with completely resolved mutational status. In 24 (13%) of these patients, testing of blood DNA showed a constitutional RB1 mutation. The distribution of age at diagnosis was not different between patients with and without a constitutional mutation. However, patients with loss of the maternally inherited RB1 allele had an earlier age at diagnosis than patients with loss of the paternally inherited RB1 allele. Our data show that early age at diagnosis does not identify patients with isolated unilateral retinoblastoma that have a higher risk of being carriers of a RB1 gene mutation. Our findings suggest that, at least in some patients, age at diagnosis is modified by a parent-of-origin effect.

Age of Onset↗
PubMed2005

Normalization for Affymetrix GeneChips.

OBJECTIVES: The high density oligonucleotide microarrays from Affymetrix (Affymetrix GeneChips) are very popular in biomedical research. They enable to study the expression of thousands of genes simultaneously. In experiments with multiple arrays, normalization techniques are used to reduce the so-called obscuring variation, i.e. the technical variation that is of non-biological origin. Several different normalization methods have been proposed during the last years. METHODS: We review published results about the comparison of normalization methods proposed for Affymetrix GeneChips. RESULTS: The quantile normalization seems to perform favorably regarding precision (low variance), accuracy (low bias), and practicability (low computing time). However, according to very recent results, this normalization method can have an impact on the biological variability and, therefore, appears to be less than optimal from this point of view. CONCLUSION: Although the quantile normalization may be recommendable, more investigations based on more data sets are needed so that the different normalization methods can be evaluated on widely differing data.

Algorithms↗
PubMed2001

The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis.

BACKGROUND: The beneficial effects of phosphodiesterase 4 (PDE4) inhibitors in allergic asthma have been shown in previous preclinical and clinical studies. Because allergic rhinitis and asthma share several epidemiologic and pathophysiologic factors, PDE4 inhibitors might also be effective in allergic rhinitis. OBJECTIVE: The main objective of this study was to investigate the efficacy of oral roflumilast (500 microg/day) in allergic rhinitis. METHODS: In a randomized, placebo-controlled, double-blinded, crossover study, 25 subjects (16 male, 9 female; median age, 28 years) with histories of allergic rhinitis but asymptomatic at screening received roflumilast (500 microg once daily) and placebo for 9 days each with a washout period of at least 14 days in between treatment periods. In each of the treatment periods, controlled intranasal allergen provocation with pollen extracts was performed daily beginning the third day of treatment, each time approximately 2 hours after study drug administration. Five and 30 minutes after each allergen provocation, rhinal airflow was measured by means of anterior rhinomanometry and the subjective symptoms obstruction, itching, and rhinorrhea were assessed by means of a standardized visual analog scale. RESULTS: Rhinal airflow improved almost consistently during the 9 days of roflumilast treatment, and it was significantly higher at study day 9 on roflumilast in comparison with placebo, a result also found for itching and rhinorrhea. With respect to the subjective obstruction score, a significant difference in comparison with placebo could be demonstrated within 4 days. CONCLUSION: This study shows that a PDE4 inhibitor, roflumilast, effectively controls symptoms of allergic rhinitis. Thus PDE4 inhibitors might be a future treatment option not only in allergic asthma but also in allergic rhinitis or the combination of the 2 diseases.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Asthma management: the challenge of equivalence.

Increasing prevalence and severity of asthma worldwide encourage the development of new antiasthmatic drugs, alternative treatment regimens and improved formulations of established drugs. Whereas the efficacy of new chemical entities (NCEs) is usually demonstrated by superiority over placebo or a subtherapeutic dose of the active drug, equivalence concepts have to be used in the following situations: the need to replace chlorofluorocarbon (CFC) propellants for inhalative asthma medications by suitable alternatives, and the need to demonstrate that an alternative treatment regimen is not clinically inferior to an established reference treatment. To cover both situations, the recent ICH guidance on biostatistics clearly distinguishes between two-sided equivalence trials and one-sided non-inferiority trials. In this context, non-inferiority always means "not inferior by a clinically relevant amount". After having confirmed non-inferiority, superiority of the alternative test treatment over the reference treatment can additionally be tested without the need to adjust the significance level. The definition of equivalence acceptance limits becomes crucial, particularly in studies conducted in the flat range of the dose-response curve of inhaled steroids. In order to assess the non-inferiority of steroid sparing add-on treatments we propose a one-sided test based on post-/pre-ratios which have substantially reduced coefficients of variation compared to the post-treatment values themselves. The non-inferiority acceptance limit of 0.90 - as opposed to 0.80 in bioequivalence assessment - reflects clinically irrelevant changes of lung function variables. The proposed methodology is illustrated by 2 examples from randomized, double-blind, parallel-group studies comparing inhaled steroid plus theophylline versus doubling the steroid dose in asthmatics who are symptomatic on low-dose inhaled steroid.

Administration, Inhalation↗
PubMed1997

Improved odds ratio estimation by post hoc stratification of case-control data.

We propose a logistic regression analysis of unmatched or frequency matched case-control studies with conditional maximum likelihood estimation through post hoc stratification. In this model fewer parameters have to be estimated. With a simulation study we show that parameter estimates have smaller variance and are less biased. Also, the residual confounding effect was quantified. A more refined post hoc stratification reduces computing time, but to the cost of a larger bias and a loss in efficiency. The model was also applied to data of unmatched case-control studies on laryngeal cancer, oesophageal cancer and lung cancer.

Case-Control Studies↗
PubMed1986

Utilization of methionine and N-acetyl-L-cysteine during long-term parenteral nutrition in the growing rat.

Utilization of methionine and N-acetyl-L-cysteine as a source of cysteine was tested in growing rats receiving total parenteral nutrition for four weeks. The three solutions tested were isonitrogenous and isocaloric. One of the solutions contained an adequate amount of L-methionine, in the other two, two thirds of the L-methionine was substituted by a corresponding amount of either glycine or N-acetyl-L-cysteine. Weight gain and N-balance were similar under the infusion with either the adequate amount of L-methionine or the N-acetyl-L-cysteine substituted. The solution in which two thirds of the L-methionine was replaced by glycine yielded only half of the weight gain and correspondingly reduced values for N-balance. The daily urinary excretion rate for N-acetyl-L-cysteine was 4.6% of the infused amount. Urinary excretion rates of the other amino acids and the plasma amino acid pattern was affected differently by the three solutions. The results indicate that cysteine is more rapidly available from N-acetyl-L-cysteine than from L-methionine when administered intravenously.

Acetylcysteine↗
PubMed1986

[Biological availability of glutamine from N-acetyl-L-glutamine in intravenous administration. Studies in the rat].

Glutamine may be important especially in the catabolic patient, due to its universal role in transamination reactions. Because of its instability, until presently, glutamine is not included in amino acid solutions for parenteral nutrition. The availability of glutamine from the stable derivate N-acetyl-L-glutamine is investigated under the condition of a long-term parenteral nutrition by means of growth, N-balance, and amino acid concentrations in plasma, muscle and urine. For this purpose 2 groups of young healthy male rats (n = 6) are maintained entirely by parenteral nutrition for 12 days. Both groups are given 0.8 g N/kg/24 h as an amino acid solution without containing glutamine. Only one of the groups was supplied additionally with 0.4 g N as N-acetyl-L-glutamine. This resulted in a weight gain of 33 +/- 1.5 g and a cumulative N-balance of 1.5 +/- 0.045 g. In the group in which no acetyl-L-glutamine is given, weight gain is 27 +/- 1.8 g (p less than 0.05) and cumulative N-balance amounts only 1.16 +/- 0.034 g (p less than 0.001). In plasma and urine the amino acid concentrations are significantly elevated for the essential one in this group. The results indicate a good availability of glutamine from N-acetyl-L-glutamine when given intravenously to the rat.

Amino Acids↗
PubMed1985

Utilization of N-acetyl-L-tyrosine and glycyl-L-tyrosine during long-term parenteral nutrition in the growing rat.

Utilization of N-acetyl-L-tyrosine and glycyl-L-tyrosine as a source of tyrosine in infusion solutions was tested in rats receiving total parenteral nutrition for 4 wk. The four solutions tested were isonitrogenous and isocaloric. One of the solutions contained an adequate amount of L-phenylalanine; in the other three, two-thirds of the phenylalanine was replaced by a corresponding amount of either glycine, glycyl-L-tyrosine or N-acetyl-L-tyrosine. No differences in weight gain or N-balance could be detected as a result of administering either the solution with glycyl-L-tyrosine or with N-acetyl-L-tyrosine in place of the solution containing an adequate phenylalanine content. The solution in which two-thirds of the L-phenylalanine was replaced by glycine yielded only half of the weight gain and correspondingly reduced values for N-balance. Daily urinary excretion rates for N-acetyl-L-tyrosine and glycyl-L-tyrosine were 11% and 0.5%, respectively, of the infused amount. Plasma amino acid pattern was affected differently by the four solutions. The results indicate that both N-acetyl-L-tyrosine and glycyl-L-tyrosine are efficiently utilized by the rat during total parenteral nutrition.

Amino Acids↗
PubMed1984

Endogenous 3-methylhistidine excretion in healthy women and men with reference to muscle protein metabolism.

Presently 3-methylhistidine excretion is widely used for monitoring the metabolic status of patients during different kinds of clinical conditions. Aim of the study was to reconsider its predicative value on the basis of a larger collective of healthy persons and to find a standardization independent from sex. Therefore endogenous 3-methylhistidine release of 40 healthy adults (24 women and 16 men) was measured and related to body weight, body surface area, arm muscle circumference, and nitrogen and creatinine excretion. A positive correlation could be observed only for 3-methylhistidine and creatinine excretion and that to the same extent both for females and males. Assuming that the excreted 3-methylhistidine is mainly originating from muscle protein the calculated daily protein breakdown amounted for women 39.9 g and 68.1 g for men. No difference between females and males could be observed in the percentual turnover of myofibrillar protein which has been estimated with 0.90 and 0.98 respectively. We interpret our results saying that endogenous 3-methylhistidine excretion is a valuable indicator for muscle protein breakdown in humans with intact kidney function. For the assessment of muscle proteolysis by 3-methylhistidine excretion in heterogenous groups of patients it is recommended to use the 3-methylhistidine/creatinine ratio or the percental turnover of myofibrillar protein.

Adult↗
PubMed1984

The metabolic status of internal intensive care patients as indicated by 3-methylhistidine excretion and nitrogen balance.

The metabolic status of 15 intensive care patients receiving a standardized total parenteral nutrition regimen was followed up to 15 days immediately after admission by measuring 3-methylhistidine, total nitrogen, and creatinine excretion. The average 3-methylhistidine excretion was within the normal range during the first 3 days, rising on day 4 and reached a maximum of 70% above normal values on day 5. It declined to within normal range thereafter in most of the patients. Mean values for creatinine excretion remained relatively constant within the normal range throughout the study. During all days 3-methylhistidine was negatively correlated with N-balance. It is concluded that these patients had increasing catabolism with a maximum on day 5 and that the catabolic condition was associated with an increased muscle protein breakdown.

Journal Article↗
PubMed1984

[Experimental model for long-term trials of parenteral nutrition in the growing rat].

Young male Sprague-Dawley rats (weighing approximately 170 gs) are entirely maintained by parenteral nutrition over a period of 4 weeks. The nutrient solution - a mixture of amino acids, glucose, fat, electrolytes, vitamins, and trace elements in a composition optimal for rats - is infused by means of a roller pump through a catheter leading to the vena cava and having its outlet in the midscapular region. The animals are provided with a little harness and kept in metabolic cages. They are freely movable during the entire infusion period. The average weight gain with an energy supply of 350 kcal and 1 g N/kg/24 h was recorded to be 3.8g/day. Since the requirement of nitrogen and energy per unit of body weight decreases with growth, nitrogen balance becomes increasingly positive in the course of the experimental period. Cumulative nitrogen retention during 24 days was 4.23 g. Operation techniques, treatment of the animals and composition of the infusion solutions are described in detail.

Aging↗
PubMed1984

[Effect of the composition of the diet on the excretion of 3-methylhistidine and creatinine in urine].

3-Methylhistidine in a defined amount of meat, consumed by 7 healthy persons is excreted quantitatively in the urine within 2 days. Simultaneously recorded creatinine excretion remained constant in 4 of the participants while in 3 cases a considerable increase was observed during the day of meat consumption. An increase in nitrogen excretion as a result of meat consumption was observed in 5 out of 7 persons.

Adult↗
PubMed1983

[Inpatient after-care measures in the framework of cancer after-care, organizational and legal gaps].

Inpatient measures are an important element of cancer aftercare. The statutory bases are contained in the various branches of the pensions and sickness insurance systems, as well as in the Federal Social Assistance Act. The establishment of working groups of the financially responsible institutions has, in many parts of the Federal Republic of Germany, entailed decisive improvements in the potentialities of inpatient aftercare measures. Speedier and intensified communication and cooperation among all persons and agencies involved are needed.

Aftercare↗