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Biomedical subjects

S Huber

Publications and source records attributed to S Huber.

At least 91 records · Page 5Linked to original sources
PubMed1994

The effect of deprenyl and tocopherol on cognitive performance in early untreated Parkinson's disease. Parkinson Study Group.

We conducted prospective cognitive assessments over 14 +/- 6 (mean +/- SD) months of observation as part of the multicenter trial Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP), which involved 800 patients with early untreated Parkinson's disease. We administered tests that measured memory, visuospatial, and frontal lobe functions. Subjects were randomly assigned to receive placebo, deprenyl (10 mg/d), tocopherol (2,000 IU/d), or both deprenyl and tocopherol. We analyzed treatment effects using annualized rates of cognitive change. We performed exploratory analyses to identify potential clinical and demographic correlates of cognitive performance. There was no significant effect of either deprenyl or tocopherol on cognitive test performance. In early untreated Parkinson's disease, cognitive performance appears to be stable and unrelated to either motor deterioration or treatment with deprenyl or tocopherol.

Aged↗
PubMed1994

Perioperative infusion of nifedipine and metoprolol provides antiischemic and antiarrhythmic protection in patients undergoing elective aortocoronary by-pass surgery.

A randomised study was performed on 70 patients undergoing elective coronary by-pass procedure to examine whether the combined, perioperative, 24-hour infusion of nifedipine and metoprolol reduces the incidence of perioperative myocardial ischemia and arrhythmias. The control group received nifedipine only. Repeated assessments of serum enzyme levels and 12-lead-ECG together with a 3-channel Holter monitoring over 48h were used to classify perioperative myocardial ischemia and supraventricular and ventricular arrhythmias. The two groups did not differ with respect to their demographic data, extracorporeal circulation, aortic cross-clamping time, or number of distal anastomosis. No perioperative myocardial infarction in either group was detected. However, a significantly lower incidence of transient ischemic event was observed in the NM group as compared transient ischemic events was observed in the NM group as compared to the N group. In addition, there was a tendency towards lower CK-MB-level and peak-values of CK- and CK-MB-enzymes in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia and atrial flutter/fibrillation in the NM group as compared to the N group. In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single-drug regimen with nifedipine.

Arrhythmias, Cardiac↗
PubMed1993

Transformation of human T-cell clones by Herpesvirus saimiri: intact antigen recognition by autonomously growing myelin basic protein-specific T cells.

Herpesvirus saimiri has recently been shown to immortalize human T cells. It was unknown, however, whether Herpesvirus saimiri transformation affects T-cell receptor (TCR) expression and signal transduction. In the present study, we have transformed CD4+ human T-cell clones specific for human myelin basic protein. The transformed T cells were grown in interleukin 2 and divided in the absence of antigen and antigen-presenting cells. They retained the membrane phenotype of activated T cells and secreted the cytokines interferon gamma and lymphotoxin, but interleukin 4 was not detected. Further, the transformed T cells continued to express the original TCR as demonstrated by TCR variable-region-V beta-specific monoclonal antibodies and TCR sequencing. Antigen-specific recognition and signal transduction by the TCR were demonstrated by myelin-basic-protein-induced HLA-DR-restricted secretion of interferon gamma and lymphotoxin and by myelin-basic-protein-specific proliferation. Antigen specificity and reactivity have been maintained for > 1 year after transformation. Transformation with Herpesvirus saimiri now allows the production of virtually unlimited numbers of (auto)antigen-specific T cells expressing functional TCR and a stable membrane phenotype. This technology will facilitate studies of the pathogenesis of putative autoimmune diseases, such as multiple sclerosis, and may be of help in TCR-targeted immunotherapy.

Antigens, CD↗
PubMed1993

A linear 16 pS Cl- channel in the apical membrane of Caco-2 cells.

A linear Cl- channel with a mean conductance of 16.3 +/- 0.4 pS (n = 7), as determined for inwardly directed currents in the cell-attached mode, was identified by the patch clamp technique in the apical membrane of Caco-2 cells in the early stage of postconfluential differentiation. This channel exhibited a low spontaneous activity (in 3 out of 137 experiments) and was not activated by strong polarization of the holding potential. After stimulation of the cAMP signal transduction cascade at different levels the 16 pS Cl- channel was activated in 7 out of 67 experiments during continuous cell-attached recording and remained active after excision of the patch. This channel differed markedly from both a linear low conductance Cl- channel and an intermediate conductance, outwardly rectifying (ICOR) Cl- channel, already reported for Caco-2 and other colonic cell lines. Thus the 16 pS channel may represent a further type of apical Cl- channel in colonocytes.

Adenocarcinoma↗
PubMed1993

Simultaneous assessment of cardiac output with pulsed Doppler and electromagnetic flowmeters during cardiac stimulation.

The aim of this study was to test the accuracy of cardiac output assessment by Doppler and electromagnetic flowmetry in dogs during states of (1) marked enhancement in cardiac output, which was obtained by means of either isoprenaline infusion or treadmill exercise, or (2) reduction in cardiac output obtained by administration of phenylephrine. Additionally, in vitro comparisons were undertaken between Doppler and electromagnetic flow-probes and assessment of flow by direct volumetric measurement. These in vitro experiments showed a good correlation between timed volume collections and electromagnetic flow assessment up to high flow velocities. Doppler flow measurements underestimated the flow at high velocities. In both the resting dog and after phenylephrine, that is, at states with low heart rate and cardiac output, the waveforms of electromagnetic flow and Doppler velocity were similar for both phasic and mean flow, respectively. During states of cardiac stimulation Doppler flow showed a decrease in maximum velocity in the ascending aorta. Due to this decrease in peak flow velocity, mean Doppler blood flow did not increase despite of increased heart rate. This result cannot be explained on the basis of the deviation of Doppler measurements at high velocities in the in vitro experiments. Although our results are in contradiction with earlier studies, electromagnetic assessment seems to be more reliable in blood flow measurements in the ascending aorta. Hence, Doppler flow measurements should not be used uncritically for such quantitative flow assessment in large vessels as determination of cardiac output.

Animals↗
PubMed1993

Combined perioperative infusion of nifedipine and metoprolol provides antiischemic and antiarrhythmic protection in patients undergoing elective aortocoronary bypass surgery.

A randomized study was performed on 70 patients undergoing elective coronary bypass surgery to examine whether the combined, perioperative, 24-hour infusion of the calcium-channel blocker nifedipine (10 micrograms/kg/h) and the beta 1-blocker metoprolol (12 micrograms/kg/h) reduces the incidence of perioperative myocardial ischemia and arrhythmias (group NM, n = 34). The control group received nifedipine only (n = 36). Repeated assessment of serum enzyme levels (CK, CK-MB) and 12-lead ECG, together with 3-channel Holter monitoring over 48 h were used to define perioperative myocardial ischemia (transient ischemic event, myocardial infarction) and supraventricular and ventricular arrhythmias. The two groups did not significantly differ with respect to preoperative anamnestic and surgical data. No perioperative myocardial infarction was detected in either group. However, a significantly lower incidence of transient ischemic events was observed in the NM group as compared to the nifedipine group (3% versus 11%; p < 0.05). In addition, there was a tendency towards lower CK-MB levels and peak-values of CK- and CK-MB in the NM group. With regard to perioperative dysrhythmias, there was a significantly lower incidence of sinus tachycardia (9%) and atrial flutter/fibrillation (6%) in the NM group as compared to the nifedipine group (33 and 27%, p < 0.05). In addition, postoperative heart rate was lower in the NM group starting from the 6th hour after opening of the aortic cross-clamp. In conclusion, the combined perioperative infusion of nifedipine and metoprolol is superior in preventing perioperative myocardial ischemia and decreasing the incidence of supraventricular arrhythmias as compared to a single-drug regimen with nifedipine.

Aged↗
PubMed1993

T lymphocyte responses in CVB3-induced murine myocarditis.

Three monoclonal antibodies (mAB) to group A streptococcus M5 serotype (mAB 36.2.2, 49.8.9 and 54.2.8) cross-reactivity bind to various heart antigens (including myosin, tropomyosin and vimentin) and neutralize a myocarditic variant of coxsackievirus B-3 (Nancy) (CVB3). The existence of shared antigenic epitopes between the two distinct infectious agents and the heart implies that antigenic mimicry may form the foundation of the autoimmune response. Plaque purified variants of CVB3 were isolated with these streptococcal mAB. The wild-type virus (H3) and the virus variants made with mABs 36.2.2 (H3-36) and 54.2.8 (H3-54) caused significant myocarditis in Balb/c (H-2d) mice, but not in CBA (H-2k) animals. The virus variant made with mAB 49.8.9 (H3-49) caused myocarditis in CBA, but not in Balb/c mice. No significant differences in virus concentrations in the heart were detected with any of the virus variants. Cytolytic activity of mesenteric lymph node cells generally correlated to the severity of myocarditis in the infected animals. Using overlapping synthetic peptides of the CVB3 VP1 protein, mAB 49.8.9 was shown to bind preferentially peptides 6, 8, 11, and 12. T lymphocytes from H3 infected mice proliferated to VP1 peptides 1, 3, 9, 13, 14, and 21. To determine whether immunity to specific peptides could affect CVB3 pathogenicity, Balb/c mice were immunized with VP1 peptides 1, 3, 6, 13, 14 and 21 in complete Freund's adjuvant (CFA) then infected with 5 x 10(4) PFU CVB3 14 days later. Pre-immunization of animals with (a) peptide 1 resulted in a significant decrease in virus titers in the heart, (b) peptides 3, 13 and 21 increased animal mortality and lymphocyte mediated cytotoxicity to uninfected cardiocyte targets, and (c) peptides 3 and 21 resulted in significant increases in myocarditis compared to animals given virus without pre-immunization.

Amino Acid Sequence↗
PubMed1992

[Toxic epidermal necrolysis (Lyell's syndrome) after rubella].

Rubella was confirmed clinically and serologically in a 14-year-old boy who had been admitted with mild general symptoms and an exanthematous rash presenting with medium size maculae. Within only three days the exanthema had faded. Five days later the boy again became ill with high fever (40 degrees C) and renewed erythema with at first irregular then rosette-like and widely confluent spots. On admission several nonspecific inflammatory signs were markedly elevated (erythrocyte sedimentation rate, C-reactive protein, alpha-globulin). There were mild abnormalities of left-ventricular repolarization at the electrocardiography. The skin changes were progressive and at first interpreted as erythema exudativum multiforme. Fever persisted, despite antibiotic treatment, and signs of epidermolysis appeared. After the diagnosis of non-staphylogenic Lyell's disease was made high-dosage prednisolone administration was begun (initially 3 mg/kg in 6 hours, then 2.5 mg/kg daily for 8 days). The patient's condition and the electrocardiographic findings returned to normal within 2 days. The epidermolysis was arrested within a few hours and the blisters dried out within 24 hours. There were no complications. Since no drugs were given before the second day of epidermolysis being noted, it is highly likely that rubella precipitated Lyell's disease.

Adolescent↗
PubMed1992

Influence of alpha 1-adrenoceptor blockade and/or 5-HT1A agonism on blood pressure and heart rate at rest and during exercise in hypertensive dogs.

1. Antihypertensive effects resulting from alpha 1-adrenoceptor blockade and stimulation of central nervous 5-HT1A receptors were compared with the effects arising from stimulation of 5-HT1A receptors alone during arterial hypertension. 2. Urapidil and 5-methyl-urapidil were less effective in decreasing arterial blood pressure than the lowest dose of the selective 5-HT1A receptor agonist, flesinoxan. After the higher dose of urapidil, a certain dampening of barareceptor reflex was found which was also seen with flesinoxan. 3. Flesinoxan was the only drug which did not reduce the exercise-induced increase in systolic arterial blood pressure. 4. Stimulation of 5-HT1A receptors alone, which is assumed to occur with flesinoxan, exerted antihypertensive activity only at low doses, without inducing reflex tachycardia at rest. 5. Only the combined effects of alpha 1-adrenoceptor blockade and 5-HT1A receptor stimulation, as assumed to occur with urapidil and 5-methyl-urapidil, lead to both a decrease in arterial blood pressure at rest and during exercise.

Adrenergic alpha-Antagonists↗
PubMed1991

Cardiovascular and side effects of flesinoxan in conscious hypertensive dogs. Modulation by prazosin.

Previous studies on anaesthetized animals indicate that flesinoxan exerts hypotensive effects via stimulation of central 5-HT1A receptors. The purpose of the present study was to investigate the cardiovascular and side effects of flesinoxan in conscious, renal hypertensive dogs at rest and during exercise. Animals were pretreated with prazosin (2.5 or 7.5 nmol/kg) to verify a reduction of dose-dependent side effects, as occurred in normotensive dogs. A decrease in blood pressure without reflex tachycardia was observed only with the lower dose of flesinoxan (0.1 mumol/kg). The higher dose (0.2 mumol/kg) led to an increase in blood pressure and heart rate. The increase in heart rate during exercise was diminished by 0.2 mumol/kg flesinoxan. Pretreatment with prazosin resulted in an additive hypotensive effect at rest. Side effects, occurring primarily after the higher dose of flesinoxan, were not influenced by prazosin. It is concluded that flesinoxan is not likely to be efficacious in antihypertensive therapy.

Animals↗
PubMed1991

Alpha 1-adrenoceptor blockade and/or 5-HT1A agonism during treadmill exercise in dogs.

1. The hypotensive effects of alpha 1-adrenergic blockade and/or stimulation of central nervous 5-HT1A receptors were studied using drugs with different affinity for central nervous 5-HT1A and peripheral alpha 1-adrenoceptors. Urapidil, 5-methylurapidil, flesinoxan and 8-OH-DPAT were compared under states of different activation of the autonomic nervous system, i.e. at rest and during graded treadmill exercise. 2. The rank order of hypotensive potency as derived from the most extensive decrease in resting diastolic arterial blood pressure was urapidil greater than 5-methylurapidil greater than flesinoxan much greater than 8-OH-DPAT. 3. The reflex increase in heart rate due to the decrease in arterial blood pressure at rest was suppressed after 0.1 mumol kg-1 flesinoxan. 4. The reflex increase in heart rate due to the decrease in arterial blood pressure at rest was less accentuated after high doses of urapidil and 5-methylurapidil. 5. During exercise both 5HT1A receptor agonists, flesinoxan and 8-OH-DPAT, decreased sympathetic tone. 6. The combined effects of alpha 1-adrenoceptor blockade and 5-HT1A receptor stimulation (urapidil and 5-methylurapidil) result in distinct decreases in blood pressure and slight suppression of reflex tachycardia at rest after high doses. Stimulation of 5-HT1A receptors alone (flesinoxan) suppresses reflex tachycardia by modulation of baroreceptor reflex and at high dose also diminishes exercise-induced increase in sympathetic tone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting.

A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗
PubMed1990

[Cardiovascular pharmacology. An example of the need of clinically relevant pharmacological research].

Like all other scientific disciplines, preclinical pharmacological research is subject to permanent changes. New measuring devices and the possibility of continuous on line data acquisition have markedly influenced basic research in this field. Another aim of modern cardiovascular pharmacology is the testing of promising drugs in clinically relevant animal models of disease, particularly under conditions, referring to the everyday situation in patients, e.g. physical activity. Investigations carried out in this way allow an exact assessment of the clinical efficacy of new drugs, and are, thus, clearly indispensable, also from the ethical point of view, before primary evaluation of the drug in man.

Angina Pectoris↗
PubMed1990

Human tumor cell lines express low levels of oncomodulin.

Different human carcinoma cell lines were screened for the presence of Ca2(+)-binding oncomodulin. A specific polyclonal antibody was raised against a synthetic peptide (amino acids 99-108) of oncomodulin coupled to hemocyanin. Extracts of tumor cell lines (several human, one rat) were analyzed for the presence of oncomodulin by immunoblotting. A strong immunoreaction of oncomodulin was obtained in chemically transformed rat fibroblasts (T14c) in contrast to all human tumor cell lines investigated, where no immunoreaction was obtained. These results suggest that oncomodulin cannot be used in diagnostics of human tumors.

Calcium-Binding Proteins↗
PubMed1990

Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia.

We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period.

Blood Pressure↗
PubMed1990

A qualitative and quantitative method for in situ characterization of the inflammatory response in experimental myocarditis.

Coxsackie virus B3 causes myocarditis in Balb/c inbred mice. In this model mortality is about 60% on day 7 and 95% on day 12 after inoculation. Significant inflammatory infiltrates appear on day 7. Recent research has focused on the immune response to explain the ensuing tissue damage. Thus we were interested in mapping cellular interaction and time course to understand the development of a possible autoimmune attack. By a newly developed immunohistochemical staining technique single lymphocytes could be visualized and different lymphocyte subpopulations enumerated. Stained cells were easily detectable and readily distinguishable from non-stained cells. Before day 7 Th cells could only occassionally be seen. The number of pan T lymphocytes increased almost 10-fold from day 7 to 12. The T helper/T killer ratio did not change significantly but indicated a predominant increase in Tk-cells. The B cell population also increased, roughly about ten times. The number of class II positive cells was constant. No expression of Il-2 receptor was found. In preliminary studies, exercise and methylprednisolone treatment tended to influence the expression of class II antigens. Cyclophosphamide and cyclosporine A reduced the number of inflammatory cells more than 10-fold. No clear concurrent reduction in mortality was observed.

Animals↗
PubMed1990

Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group.

The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.

Adult↗