Biomedical subjects
A Hoffmann
Publications and source records attributed to A Hoffmann.
[The influence of papaverine on functions of the blood platelets].
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[On the release of biogenic amines from blood platelets by animal poisons].
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[On the effect of subtilisin on the elimination of biogenic amines from blood platelets].
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["The human factor in relation to safety." Study of the practical value, in the prevention of work accidents, of clinical, biological and psychometric tests in the iron industry of Luxembourg].
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[Studies on the mechanism of the amine liberating action of proteolytic enzymes in blood platelets].
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[Suitability of the plant protease bromelain for substitution therapy in digestive disorders].
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[Blood pressure and smoking habits of 14-16-year-old students in Basel].
In a representative sample of Basle eight grade students (14-16 years) blood pressure measurements were correlated with smoking habits. Mean pressure was 122 68 mm Hg for 358 boys and 118/68 mm Hg for 387 girls (p 0,005). 40 of the boys (11%) and 56 of the girls (14%) reported themselves as smoking one or more cigarettes daily. They were found to have lower systolic and diastolic pressure values than non-smokers. These results confirm findings in adults, where smoking was reported to have an inhibiting effect on blood pressure rise in the case of weight gain.
Comparison of the cardiovascular effects of phentolamine, sodium nitroprusside and nitroglycerin in anaesthetized cats (comparison of vasodilators).
The effects of phentolamine (PH), sodium nitroprusside (NP) and nitroglycerin (GTN) were compared in experiments on anaesthetized cats. All three agents diminished vascular resistance and lowered blood pressure, although they differed in the intensity of their effects (NP greater than PH = GTN) and in the steepness of their dose-response curves (NP greater than PH greater than GTN). NP and GTN did not cause consistent changes in heart rate and dP/dt, whereas PH produced marked, dose-dependent increases in these two variables and in cardiac output, which was augmented to a lesser extent by NP and not affected by GTN. It is concluded that whereas the beneficial therapeutic effects of NP and GTN are presumably due exclusively to the reduction of preload and afterload, PH has an additional cardiostimulant action.
Can oral contraceptive steroids influence the elimination of nifedipine and its primary pryidine metabolite in humans?
OBJECTIVE: To investigate the influence of oral contraceptives on cytochrome P450 3A4 (P450NF) activity. METHODS: In 23 healthy women, the pharmacokinetics of nifedipine and its main metabolite dehydronifedipine in plasma were assessed after a single oral dose, prior to and after intake of one of two oral contraceptive formulations, one containing 2 mg dienogest and 0.03 mg ethinylestradiol (group A) and the other containing 0.125 mg levonorgestrel and 0.03 mg ethinylestradiol (group B). RESULTS: While the intake of two oral contraceptives for 21 days did not influence the plasma concentration-time curve of unchanged nifedipine, mean AUC0-23.5 h and the mean Cmax values of dehydronifedipine were significantly lower in both groups tested/(24% in group A and 25% in group B). This observation may indicate a reduced formation rate of metabolites and reflects an inhibition of cytochrome P450 3A4 activity. The activation of the same or other metabolic degradation mechanism(s) could explain this result. CONCLUSION: The investigation presented demonstrates the importance of metabolite measurement when in vivo studies are undertaken to investigate different influences on drug metabolizing ability.
Effect of drugs that alter alertness and emotionality on the novelty response of a weak electric fish, Gymnotus carapo.
Weak field electric fish respond to alerting stimuli with a transient increase in the frequency of electric organ discharge (novelty response). In an attempt to demonstrate the influence of different degrees of alertness and of emotionality on the novelty response of Gymnotus carapo, we studied the variations in the magnitude of this response induced by the application of an electric stimulus to the water of the experimental box using a pair of electrodes, before and after intramuscular injections of d-amphetamine (1-2 and 4 mg/kg), sodium pentobarbital (10-20 and 30 mg/kg), diazepam (1-2 and 4 mg/kg), beta-carboline (2 mg/kg), and saline. After d-amphetamine injection the animal presented increased somatic motility but no changes in electric organ baseline firing rate or in response to the alerting electric stimulus. Sodium pentobarbital induced a partial loss of posture and a reduction of fin and operculum movements, as well as a reduction of baseline firing rate and of the response to the alerting electric stimulus, with frequent interruptions in electric organ firing. Beta-carboline caused increased motility, but no changes in basal firing rate or in response to the alerting stimulus. Diazepan-injected fishes remained still throughout the experiment, and some of those threated with the higher dose (4 mg/kg) presented interruptions on electric organ discharges in response to stimulation but no change on baseline firing rate. The data suggest that a reduction of the degree of alertness by the barbiturate and a decrease in emotionality and/or stress by the benzodiazepine interfere with the novelty response. The possible site of action of the drugs is discussed.
Opposing effects of nitric oxide on different connexins expressed in the vascular system.
Gap junctions--clusters of intercellular channels built by connexins (Cx)--are thought to be important for vascular cell functions such as differentiation, control of tone, or growth. In the vascular system, gap junctions can be formed by four different connexins (Cx37, Cx40, Cx43 and Cx45). The permeability of these connexin-formed gap junctions determines the amount of intercellular coupling and can be modulated by several vasoactive substances such as prostacyclin or nitric oxide (NO). We demonstrate here that NO has specific effects on certain connexins. Using two different techniques--injection of a fluorescent dye in single cells as well as detection of the de novo formation of gap junctions by a flow cytometry based technique--we found that NO decreases the functional coupling in Cx37 containing gap junctions whereas it increases the de novo formation of gap junctions containing Cx40. We conclude that NO, in addition to its known vasomotor effects, has a novel role in controlling intercellular coupling resulting in opposing effects depending on the specific connexin expressed in the cells.
A melatonin preparation with a pulsatile liberation pattern: a new form of melatonin in replacement therapy.
Using melatonin (MLT) as a circadian synchroniser in humans to treat rhythm disorders, it is desirable to have controlled-release dosage forms. Following in vitro liberation tests, one fast-release form containing 5 mg MLT (capsule A) and two oral pulsatile-dosage forms containing 10 mg MLT each (capsules B and C) were studied in a randomised, single-dose, threefold cross-over study in 15 healthy male volunteers after investigation of capsule B in dogs. Mean peak concentrations of MLT in serum (pmol/ml) were reached between 0.5 h and 0.75 h: Cmax1 20.7 (A), 16.4 (B), 9.7 (C). Capsules B and C released a second MLT pulse after about 3.5 h with Cmax2 of 13.0 and 17.5 pmol/ml, respectively. The time course of the renally excreted main metabolite 6-sulphatoxymelatonin (aMT6s) correlates with that of changes in MLT serum concentrations. The kinetic profile of the delivery system is adjusted to the pattern of sleep maintenance disturbances.
A skin test for autonomic neuropathy.
Intradermal injection of 0.5 microgram histamine produced equal skin reactions in normal individuals (n = 15) and in diabetic patients with (n = 10) or without (n = 9) evidence of autonomic neuropathy as well as in patients after lumbar sympathectomy (n = 5). Addition of noradrenaline (0.1 microgram) resulted in a significantly smaller skin reaction (mean +/- SEM) in normal (101.9 +/- 10.1 vs. 136.3 +/- 6.5 mm2, p less than 0.005) and in diabetic patients without autonomic neuropathy (101.8 +/- 8.4 vs. 123.9 +/- 8.7 mm2, P less than 0.05), but remained unchanged in diabetic patients with autonomic neuropathy (131.0 +/- 9.0 vs, 130.7 +/- 8.2 mm2, n.s.) and after lumbar sympathectomy (135.2 +/- 17.5 vs 130.2 +/- 19.6 mm2, n.s.) when compared with the reaction to histamine alone. Addition of terbutaline produced similar results as observed with noradrenaline. These findings suggest a defect at the adrenoceptor level in diabetic patients with autonomic neuropathy and in patients with lumbar sympathectomy. Thus, the combined intradermal injection of histamine and the adrenoceptor agonists noradrenaline or terbutaline represents a simple and useful test for identifying patients with impaired adrenergic function.
[3 cases of human intestinal mite infestation in the South of Veracruz].
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First clinical data of a natural immunomodulator in colorectal cancer.
BACKGROUND/AIMS: MSC (trade-name AVEMAR) is a per os applicable complex of multiple, biologically active molecules obtained from fermented wheat-germ extract. Preclinical studies suggest potent anti-metastatic activity and it has a favorable toxicity profile. It has been aimed in a pilot-scale, phase II clinical study to document whether or not MSC as a support to surgery or plus chemotherapy adds any therapeutic benefit compared to the same combination without MSC in colorectal cancer. METHODOLOGY: From 1998 to June 1999, 18 control patients and 12 consecutive colorectal cancer patients respectively, were enrolled into this study. All patients underwent curative surgery. The control group (18 patients) received no other therapy or adjuvant chemotherapy alone. The MSC group (12 patients) received MSC alone or plus adjuvant chemotherapy. Until now, the median follow-up has been 9 months. RESULTS: Interim data of the study document that in the MSC group no new metastases, neither hepatic nor other, have occurred, so far. On the contrary, several new metastases have developed in the control group. CONCLUSIONS: Orally administered MSC is a potent candidate to be regarded as a supportive therapy to surgery or plus chemotherapy for colorectal cancer patients.
Dynamics of chronic active herpesvirus-6 infection in patients with chronic fatigue syndrome: data acquisition for computer modeling.
Ten adult patients with persistent active HHV-6 variant A infection and clinical chronic fatigue syndrome (CFS) were studied over a period of 24 months after initial clinical diagnosis. CFS was diagnosed according to IIIP-revised CDC-criteria as defined by the CFS Expert Advisory Group to the German Federal Ministry of Health in 1994. Changes in HHV-6 antibody titer, viral DNA load, peripheral blood T lymphocytes and subpopulations, as well as CD4/CD8 cell ratio and cell death (apoptosis) were monitored. Data were collected for comparison with respective changes in acute HHV-6 infection and as a basis for future computer simulation studies. The results showed variable but slightly elevated numbers of HHV-6 DNA copies in the blood of patients with CFS, while PBL (peripheral blood lymphocyte) apoptosis rates were clearly increased. CD4/CD8 cell ratios varied from below 1 up to values as seen in autoimmune disorders. Contrary to acute HHV-6 infection, T lymphocytes do not exhibit the usual response to HHV-6, that is elevation of mature and immature populations suggesting a certain degree of unresponsiveness. The data suggest that persistent low-dose stimulation by HHV-6 may favor imbalanced immune response rather than overt immune deficiency. This hypothesis requires confirmation through additional functional studies.
Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set.
OBJECTIVE: The definition of chronic fatigue syndrome (CFS) is still disputed and no validated classification criteria have been published. Artificial neural networks (ANN) are computer-based models that can help to evaluate complex correlations. We examined the utility of ANN and other conventional methods in generating classification criteria for CFS compared to other diseases with prominent fatigue, systemic lupus erythematosus (SLE) and fibromyalgia syndrome (FMA). PATIENTS AND METHODS: Ninety-nine case patients with CFS, 41 patients with SLE and 58 with FMA were recruited from a generalist outpatient population. Clinical symptoms were documented with help of a predefined questionnaire. The patients were randomly divided into two groups. One group (n = 158) served to derive classification criteria sets by two-fold cross-validation, using a) unweighted application of criteria, b) regression coefficients, c) regression tree analysis, and d) artificial neural networks in parallel. These criteria were validated with the second group (n = 40). RESULTS: Classification criteria developed by ANN were found to have a sensitivity of 95% and a specificity of 85%. ANN achieved a higher accuracy than any of the other methods. CONCLUSION: We present validated criteria for the classification of CFS versus SLE and FMA, comparing different classification approaches. The most accurate criteria were derived with the help of ANN. We therefore recommend the use of ANN for the classification of syndromes with complex interrelated symptoms like CFS.