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Biomedical subjects

M Weis

Publications and source records attributed to M Weis.

90 records · Page 5Linked to original sources

Corticospinal conduction studied with magnetic double stimulation in the intact human.

A group of 8 healthy normal subjects (24-36 years old, mean age 29 years) were investigated. Transcranial magnetic double stimulation of the motor cortex was carried out at different interstimulus intervals. With both stimuli suprathreshold, an attenuation of the test response was found at interstimulus intervals of less than 200 msec (target relaxed or contracted). The manifestation of this attenuation correlated with central signs in 31 patients with multiple sclerosis. This phenomenon is (at least at longer intervals) probably not a result of the refractory spinal motoneuron pool, but of a supraspinal inhibitory mechanism or lack of corticospinal drive caused otherwise. At interstimulus intervals between 10 and 30 msec, the test response increases significantly (magnetic double stimulation 10% suprathreshold, target relaxed). This result is also seen with voluntary muscle contraction and with vibration applied to a relaxed target muscle. The facilitatory effect is probably caused by slowly conducted corticospinal volleys enabling summation, with descending impulses generated by the test stimulus. With the conditioning stimulus subthreshold and target muscle relaxed an intracortical inhibition of the test response could be confirmed at short interstimulus intervals.

Adult↗

[Empirical findings with arson offenders].

Forensic, psychological and psychopathological findings on 40 arsonists, who were investigated in our psychiatric department between 1980 and 1990, are presented. The findings indicate that arsonists represent a diagnostically heterogeneous group of offenders. On the other hand, some common psychodynamic patterns can be seen; in particular, a high degree of suicidal and autoaggressive behaviour. As reported by other authors, arsonists appear to suffer from a disorder of impulse control. A historical review illustrates that since the mid-19th century a purely psychopathological model of pyromania has been found unsatisfactory, and suggests that psychodynamic aspects should not be over-emphasized. Analysis of the different motivation and abnormalities of arsonists could render the term pyromania obsolete. This requires however a radical reappraisal of the significance of psychiatric diagnosis within an anthropological framework.

Alcoholism↗

Motor potentials evoked in tibialis anterior by single and paired cervical stimuli in man.

Latencies of compound muscle action potentials evoked in lower limb muscles after transcranial stimulation shorten and amplitudes enlarge when the target muscle is contracted. After transcutaneous stimulation of the cervical cord with single electrical stimuli, the latency is not affected by muscle contraction. This is thought to be due to a lack of temporal summation at the spinal motoneurones. Results are different when paired stimuli are used. With contraction most motoneurones respond to the first cervical stimulus while in a relaxed condition they respond to the second. Temporal summation brings motoneurones to their firing threshold. Therefore, cervical double stimulation is more effective than single stimuli. It is however less powerful than cortical stimulation. Paired stimuli are most powerful at an interval of 2 ms similar to the D I-wave interval after cortical stimulation.

Action Potentials↗

Continuous multivariable monitoring in neurological intensive care patients--preliminary reports on four cases.

Evoked potential monitoring is a standard examination method in neurological intensive therapy units. Previously, multimodality observation was only possible in follow-up examinations. First experience with a new bed-side system continuously monitoring 12 neurophysiological and clinical parameters is reported. It consists of a personal computer and various stimulation units. EEG activity, median nerve somatosensory evoked potentials (SEPs) and brainstem auditory evoked potential (BAEPs) are recorded. Additionally, EEG spectral band power, heart rate, heart rate variability, intracranial pressure, body temperature, expiratory PCO2, blood pressure and transcutaneously measured oxygenation can be monitored. This paper reports on 4 exemplary cases of the 33 patients we have monitored to date, illustrating the principles and main advantages of the system. The system was developed to support the observation of ICU patients as well as to aid therapeutic decisions. It supports the clinical determination of brain death by specifying the deterioration of various neurological systems.

Aged↗

Quinone imine-induced Ca2+ release from isolated rat liver mitochondria.

Incubation of Ca2(+)-loaded rat liver mitochondria with N-acetyl-p-benzoquinone imine (NAPQI) or its two dimethylated analogues resulted in a concentration dependent Ca2+ release, with the following order of potency: 2,6-(Me)2-NAPQI greater than NAPQI greater than 3,5-(Me)2-NAPQI. The quinone imine-induced Ca2+ release was associated with NAD(P)H oxidation and was prevented when NAD(P)+ reduction was stimulated by the addition of 3-hydroxybutyrate. Mitochondrial glutathione was completely depleted within 0.5 min by all three quinone imines, even at low concentrations that did not result in Ca2+ release. Depletion of mitochondrial GSH by pretreatment with 1-chloro-2,4-dinitrobenzene enhanced quinone imine-induced NAD(P)H oxidation and Ca2+ release. However, 3-hydroxybutyrate protected from quinone imine-induced Ca2+ release in GSH-depleted mitochondria. Mitochondrial membrane potential was lost after the addition of quinone imines at concentrations that caused rapid Ca2+ release; however, subsequent addition of EGTA led to the complete recovery of the transmembrane potential. In the absence of Ca2+, the quinone imines caused only a small and transient loss of the transmembrane potential. Taken together, our results suggests that the quinone imine-induced Ca2+ release from mitochondria is a consequence of NAD(P)H oxidation rather than GSH depletion, GSSG formation, or mitochondrial inner membrane damage.

Animals↗

Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin-induced intravascular coagulation and acute lung injury in pigs.

We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Role of sulfhydryl groups in benzoquinone-induced Ca2+ release by rat liver mitochondria.

Incubation of rat liver mitochondria with benzoquinone derivatives in the presence of succinate plus rotenone has been shown to cause NAD(P)H oxidation followed by Ca2+ release. Further investigation revealed: (1)p-Benzoquinone-induced Ca2+ release was not initiated by a collapse of the mitochondrial membrane potential. However, Ca2+ release and subsequent Ca2+ cycling caused limited increased membrane permeability. (2) p-Benzoquinone-induced NAD(P)H oxidation and Ca2+ release were prevented by isocitrate, 3-hydroxybutyrate, and glutamate but not by pyruvate or 2-oxoglutarate. (3) Inhibition of pyruvate and 2-oxoglutarate dehydrogenases by p-benzoquinone was attributed to arylation of the SH groups of the cofactors, CoA and lipoic acid. Isocitrate dehydrogenase was also inhibited by p-benzoquinone, but the cofactors NAD(P)H and Mn2+ protected the enzyme. Glutamate dehydrogenase was not inhibited by p-benzoquinone. (4) Arylation of mitochondrial protein thiols by p-benzoquinone was associated with an inhibition of state 3 respiration, which was attributed to the inactivation of the phosphate translocase. In contrast, state 4 respiration, and the F1.F0-ATPase and ATP/ADP translocase activities were not inhibited. It was concluded that inhibition of mitochondrial NAD(P)H dehydrogenases by arylation of critical thiol groups will decrease the NAD(P)+-reducing capacity, and possibly lower the NAD(P)H/NAD(P)+ redox status in favor of Ca2+ release.

Animals↗

Determination of the intracellular protein thiol distribution of hepatocytes using monobromobimane derivatisation of intact cells and isolated subcellular fractions.

The derivatisation of intact rat hepatocytes with monobromobimane resulted in rapid labelling of accessible protein thiols in several subcellular fractions. The derivatisation procedure did not cause acute cytotoxicity, nor did it alter the buoyant densities of the fractions or their gross protein compositions. Quantitation of the fluorescence irreversibly associated with the fractions demonstrated considerable intracellular heterogeneity in this pool of thiols. Values were highest in cytosol (ca. 90 nmol/mg protein), intermediate in microsomes (ca. 65 nmol/mg protein) and mitochondria (ca. 45 nmol/mg protein) and lowest in a crude fraction containing both nuclei and plasma membrane (ca. 35 nmol/mg protein). Similar values were obtained from microsomes and cytosol derivatised after fractionation but there were significant increases of ca. 100% in corresponding values from isolated mitochondria and the nuclear/plasma membrane fraction. These results are discussed in terms of the dynamic fluxes in monobromobimane protein thiols during fractionation and the applicability of this noninvasive method to studies of the mechanism(s) of toxicity of reactive xenobiotics and the role(s) of protein thiols in normal cellular function.

Animals↗

Expression in Escherichia coli of active human alcohol dehydrogenase lacking N-terminal acetylation.

Human alcohol dehydrogenase (ADH, beta beta isozyme of class I) was expressed in Escherichia coli, purified to homogeneity, and characterized regarding N-terminal processing. The expression system was obtained by ligation of a cDNA fragment corresponding to the beta-subunit of human liver alcohol dehydrogenase into the vector pKK 223-3 containing the tac promoter. The enzyme, detected by Western-blot analysis and ethanol oxidizing activity, constituted up to 3% of the total amount of protein. Recombinant ADH was separated from E. coli ADH by ion-exchange chromatography and the isolated enzyme was essentially pure as judged by SDS-polyacrylamide gel electrophoresis and sequence analysis. The N-terminal sequence was identical to that of the authentic beta-subunit except that the N-terminus was non-acetylated, indicating a correct removal of the initiator methionine, but lack of further processing.

Acetylation↗

Designed inhibitors of horse liver alcohol dehydrogenase. Effect of active-site metal ion substitution.

3-(p-Butoxyphenyl)propionamide, -thioamide and -hydrazide and the formamide of p-butoxybenzylamine were tested as inhibitors of cadmium(II) and cobalt(II) active-site substituted alcohol dehydrogenase. The results agree with a direct coordination of these inhibitors except for the hydrazide to the active-site metal ion, in the enzyme-NADH-inhibitor complex. The hydrazide might be situated at some distance from the metal ion without a direct coordination bond.

Alcohol Oxidoreductases↗

[Incidence and pregnancy rates in various causes of sterility].

A precise diagnostic procedure could be done in 1,450 sterile couples in the years 1975 to 1982. The prevailing cause of sterility was female in 67 per cent, male in 22 per cent and both female and male in 11 per cent. Pregnancy rate over all was 35 per cent and after therapy 45 per cent. There was a distinct correlation between pregnancy rate, age of the patient and duration of desire for child. 73 per cent of all conceptions occurred in female sterility; 77 per cent of it in ovarian sterility. Simple therapeutic methods like gestagens or clomiphene and conversational therapy achieved the highest pregnancy rate. Only a little proportion of the pregnancy rate could be obtained by highly specialized measurements like FSH/HCG (7 per cent) or operative interventions (8 per cent). In cases of male reasons only 8 per cent of all pregnancies could be attained. 62 per cent of all pregnancies supervised were live births. Because highly specialized methods are not able to influence the rate of conceptions over all embryo transfer will be more and more the alternative method in cases of sterile couples treated without success till now.

Adult↗

Actinlike material in Pseudomonas aeruginosa.

Actinlike material was obtained from disrupted Pseudomonas aeruginosa cells by a modification of the method of Hancock and Nikaido (J. Bacteriol. 136:381-390) for isolating outer membrane vesicles. Pelleted membranes were dissolved in Laemmli sample buffer and electrophoresed in parallel lanes with purified rabbit skeletal muscle actin. The bacterial preparation migrated similarly to rabbit skeletal muscle actin. A doublet band was detectable by affinity-purified antiactin antibody in a passive transfer immunoblot. Molecular weight of the actinlike protein doublet was 60,000 to 63,000 as determined by linear regression analysis of Bio-Rad low-molecular-weight standards run on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Transmission electron microscopy of the actinlike material in high salt concentrations revealed 10- to 14-nm filaments of various lengths. Despite its ability to form filaments and to react with a polyclonal rabbit antiactin antibody, the bacterial filaments did not bind the S-1 fragment of heavy meromyosin.

Actins↗

Captopril in diuretic-treated hypertensive patients.

Eight hypertensive patients with normal renal function and receiving diuretic therapy for at least 28 days received captopril in small increasing doses (6.25, 12.5, and 25 mg). Supine and standing blood pressure (BP) and pulse rate, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured before and after captopril administration. The mean (+/- SEM) maximal decline in BP was 38/18 +/- 3/2, 34/18 +/- 4/2, and 25/17 +/- 3/2 mm Hg and occurred within 70 minutes of each of the three doses. In contrast, the duration of a 10 mm Hg or greater decrease in BP was prolonged markedly (103 +/- 5, 175 +/- 15, and 287 +/- 10 minutes) after each dose increment. After captopril, mean PRA levels increased while PAC levels fell. Transient dizziness on standing occurred in two patients, but captopril was otherwise well tolerated. Evaluation of the response to initial doses of captopril appears to be helpful in predicting maintenance requirements.

Aged↗

Multicenter comparative trial of ciprofloxacin versus cefuroxime axetil in the treatment of acute rhinosinusitis in a primary care setting. Rhinosinusitis Investigation Group.

In a primary care setting, the efficacy and safety of ciprofloxacin (CIP) 500 mg b.i.d. were compared with those of cefuroxime axetil (CA) 250 mg b.i.d., each given for 10 days, in a nationwide, open, prospective, randomized trial of 1414 adults with acute sinusitis. Patients were enrolled if they had clinically documented acute sinusitis (ie, rhinosinusitis) (<4 weeks' duration), based on the 1997 American Academy of Otorhinolaryngology--Head and Neck Surgery criteria of either two major or one major and two minor symptoms. The primary efficacy variable was clinical response (resolution or failure) at the posttherapy assessment on study days 14 through 26. The most common presenting major signs and symptoms of acute rhinosinusitis were facial congestion, nasal drainage/purulence, facial pain/pressure, and nasal obstruction/blockage. The minor symptom, headache, was more common and severe than was nasal obstruction/blockage. A total of 1219 patients were clinically evaluable. Clinical resolution was observed in 559 of 613 (91.2%) CIP-treated patients and 546 of 606 (90. 1%) CA-treated patients. The two regimens were statistically equivalent (95% confidence interval, -2.16% to 4.71%). There were 80 drug-related adverse events reported in the CIP-treated patients and 81 drug-related adverse events reported in the CA-treated patients. The main adverse events were nausea (n = 18) and diarrhea (n = 7) in patients treated with CIP and diarrhea (n = 14), nausea (n = 12), headache (n = 7), and vaginitis (n = 7) in those treated with CA. CIP 500 mg b.i.d. was found to be statistically equivalent to CA 250 mg b.i.d. in the treatment of acute rhinosinusitis.

Acute Disease↗