Biomedical subjects

W H Ziegler

Publications and source records attributed to W H Ziegler.

At least 19 recordsLinked to original sources

PubMed1992

Effect of head-down tilt bedrest (10 days) on lymphocyte reactivity.

Immunological responses of six healthy males to 10 days of head-down tilt bedrest (HDT) were assessed. Lymphocyte responsiveness was severely reduced immediately before, during, and immediately after the HDT, even though the lymphocyte numbers did not change. By contrast, delayed-type hypersensitivity was not affected. No dramatic changes were found in WBC counts and lymphocyte subpopulations, with the only exception of natural killer (NK) cells which transiently decreased immediately after HDT. Plasma cortisol levels were elevated above normal immediately before and during the HDT. The data suggest that the mitogenic response of lymphocytes was affected by psychological and fluid shift stress. These results are compared with data obtained during and after spaceflight. We conclude that the stress of HDT induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight.

Adult↗

PubMed1990

[Permeability pulmonary edema in pheochromocytoma].

We describe two patients with pheochromocytoma who developed pulmonary edema of rapid onset. The edema occurred spontaneously in the first case and during surgery for the tumor in the second patient. Since left ventricular function was normal in both patients and the protein content of the edema fluid was elevated in one patient, the conditions involved were permeability edemas.

Adrenal Gland Neoplasms↗

PubMed1990

Biochemical changes in the mother and the fetus during labor and its significance for the management of the second stage.

In 69 patients with uneventful pregnancies, term labor was studied prospectively with respect to length of second stage, number of bearing down efforts, maternal and fetal levels of lactate, epinephrine and norepinephrine. Maternal venous blood concentrations were measured in early labor and at the time of delivery while samples from umbilical artery and vein provided fetal blood. There was a significant rise of lactate and catecholamines in maternal blood during labor and at delivery fetal lactate concentration was lower than the maternal level while for epinephrine and norepinephrine fetal levels were higher. For all three compounds umbilical artery concentrations were higher than umbilical venous levels. While there was no correlation between the biochemical parameters in maternal blood and length of second stage maternal lactate and norepinephrine concentration at the time of delivery significantly correlated with the number of bearing down efforts. Umbilical artery lactate correlated with both, length of second stage and number of bearing down efforts.

Epinephrine↗

PubMed1990

Cardiovascular regulation during angiotensin converting enzyme inhibition with captopril in diabetes-associated hypertension.

Diabetes-associated hypertension is accompanied by high levels of body sodium and cardiovascular hyper-reactivity to noradrenaline. Captopril, a promising drug for the treatment of hypertension in diabetics, may influence sodium metabolism and adrenergic pathways. This possibility was investigated in 11 patients with non-azotaemic diabetes mellitus and hypertension, studied after a 3-week placebo phase and after an 8-week phase of captopril treatment (50-100 mg/day). Blood pressure, exchangeable body sodium, blood volume, plasma renin activity, angiotensin II (Ang II), aldosterone, catecholamine levels and the pressor reactivity to infused Ang II or noradrenaline were measured. Compared with placebo, captopril caused a significant decrease in arterial pressure and stimulation of plasma renin activity. Exchangeable sodium, blood volume, plasma Ang II, aldosterone, noradrenaline and adrenaline levels, the pressor and aldosterone responsiveness to infused Ang II and the pressor response to infused noradrenaline (alone or combined with atropine) were not modified. These findings suggest that in hypertensive diabetics angiotensin converting enzyme inhibition causes a marked decrease in blood pressure. The mechanism of action is unrelated to changes in body sodium or noradrenergic-dependent pressor reactivity. In the stable phase of therapy, Ang II-dependent pathways are left unaltered when captopril is administered twice a day.

Adult↗

PubMed1990

Biotransformation of moclobemide in humans.

The structure of the urinary metabolites formed after moclobemide administration in human was elucidated, and the pattern compared with that in the plasma. The metabolic pathways of moclobemide were also compared with those of structurally related substances. After oral moclobemide administration, on average 95% of the dose was recovered in the urine within 4 days, with a mean of 92% being excreted during the first 12 h. The drug is extensively metabolized: less than 1% of the dose was excreted unchanged. A total of 19 metabolites, accounting together for about 64% of the dose, was isolated and all metabolites accounting for more than 1% of the dose were identified. Consistent with other morpholine-containing compounds, metabolic pathways of moclobemide include mainly oxidative attack on the morpholine moiety, leading to a multitude of oxidation products. Four primary metabolic reactions were identified: morpholine N-oxidation, aromatic hydroxylation, morpholine C-oxidation and deamination. The major metabolites in urine are 4 carboxylic acids (M7A and M7B, M8, M9) that account for 49% of the dose. Only 2 metabolites (M3, M10) were found to be hydroxylated on the aromatic nucleus. They were excreted completely as conjugates of glucuronic and/or sulfuric acid. Conjugation in general, however, seems to be of minor importance in the overall biotransformation of the drug. The metabolite pattern in plasma was found to be qualitatively but not quantitatively similar to that observed in urine. Almost all of the main urinary metabolites were found in plasma as well. The unchanged parent compound and 2 primary oxidation products of the morpholine ring (M1, M15), which were present in urine only in trace amounts, could easily be detected in plasma.

Administration, Oral↗

PubMed1990

Effect of a herbal yeast food supplement and long-distance running on immunological parameters.

The effect of a food supplement on immunological parameters of 16 long-distance runners was tested in a randomized, double-blind and placebo-controlled trial. The supplement comprised plasmolysed herbal yeast, malt, honey, and orange juice. No statistically significant differences between the two groups regarding the following variables were detected at three sessions at rest and immediately after a 21 km run: total and differential white blood cell counts, numbers of B- and T-cells and T-subpopulations, concanavalin-A-induced lymphocyte proliferation, serum levels of immunoglobulins, neopterin, IL-2 receptors, beta 2-microglobulin, complement factor b, c4 and c3c, and c1-inactivator. These findings suggest that the effects of the tested food supplement on these parameters are negligible with respect to improvements in the immunological status of long-distance runners. The changes observed immediately after the run had a transient character. In both groups, however, low lymphocyte counts, IgG subclass 2 levels and c1-inactivator levels were noted at rest, which indicate that the immune status of endurance athletes may be affected by training.

Adult↗

PubMed1990

Application of linked DNA markers to screening families with multiple endocrine neoplasia type 2A.

There now exists a set of tightly linked markers to the gene causing multiple endocrine neoplasia type 2A. In this report we discuss the use of these markers for early and accurate prediction of gene carrier status in three different families. Factors that influence the probability of obtaining useful information with DNA markers are available family size, in particular the number of available affected individuals, and the extent of clinical and biochemical screening in the family. At present, DNA analysis has about a 3% risk of misdiagnosis; this risk is even lower if it is used in conjunction with the pentagastrin stimulation test for C-cell hyperplasia. With the combined tests, an individual at age 20 years may be scored as carrier or not with an estimated accuracy of 99%.

Adolescent↗

PubMed1989

Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans.

If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible to induce ameliorations of the syndrome by pharmacologically antagonizing a component of the GABA/benzodiazepine receptor complex. To test this possibility we administered the benzodiazepine receptor antagonist flumazenil by intravenous injection to 14 patients with hepatic encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements of the mental status in 71% of the patients. The degree of encephalopathy improved from stage IV to stage II in 4 patients and from stage IV to stage III in 2 patients. The mental status of all patients with less advanced encephalopathy (3 with stage III, 1 with stage II) also improved, but these responses were clinically less impressive. The arousal effect occurred within minutes after the injection and lasted for 1 to 2 h. Furthermore, it was associated with a significant increase of the mean electroencephalographic frequency from 4.2 to 5.2 cycle/s. Of the 8 patients who were ultimately discharged from the hospital, 7 had responded to flumazenil. No patient who died within 48 h of receiving flumazenil had shown any arousal effect. These findings strongly favor a prominent pathogenetic role of increased GABAergic tone in hepatic encephalopathy in humans and suggest that a positive response to flumazenil might be of prognostic value in predicting short-term survival in encephalopathic patients with liver disease.

Adult↗

PubMed1989

[Drug therapy of pain].

Pain represents the most frequent complaint for which patients ask for medical help. Successful treatment of acute and chronic pain syndromes largely depends on the knowledge and the therapy of the underlying disease process and on the rational use of analgesics, such as the nonnarcotic analgesic-antipyretics, the anti-inflammatory agents and the opioid analgesics. In addition, so-called 'adjuvant' analgesics of different chemical structures can be used in special clinical conditions to increase the efficacy of the common analgesics. For optimal therapy, the selection and dosing of a specific agent has to be tailored to the individual needs of the patient. For this purpose it is important to follow some general principles of pain management and to consider the relevant pharmacokinetic and pharmacodynamic properties of the various analgesics. This overview summarizes the most important pharmacological properties of the widely used analgetic drugs, with special emphasis on their risk-benefit ratio in various clinical situations.

Analgesics↗

PubMed1988

[Benzodiazepine--practice and problems of its use].

Benzodiazepines are the most frequently prescribed drugs in the Western world. About 3% of the adult Swiss population regularly use benzodiazepines for the treatment of anxiety states or for induction of sleep. All benzodiazepine agonists available exert qualitatively similar pharmacodynamic actions. They commonly activate central GABAergic neuroinhibition, thereby inducing anxiolysis, sedation/hypnosis, anticonvulsion and muscle relaxation. However, various derivatives differ in their physicochemical and pharmacokinetic properties such as lipophilicity, rate of gastrointestinal absorption, hepatic biotransformation and elimination half life. These differences among individual substances can be used clinically to optimize therapy for the individual patient. For example, the elimination half life greatly influences the frequency, intensity and type of adverse reactions such as hangover, rebound insomnia, development of tolerance and dependence as well as withdrawal symptoms. It is estimated that "low-dose dependency" develops in as many as 30 to 45% of chronically treated patients. Low-dose dependency is mainly characterized by the appearance of withdrawal symptoms after cessation of therapy. Since management of the withdrawal state is difficult and especially troublesome for the patient it is best to prevent the development of benzodiazepine dependence by prescribing these drugs less and restricting them to short-term use (7-14 days).

Anxiety↗

PubMed1988

Experimental model for the investigation of kinetic and/or dynamic interactions between drugs and ethanol in humans.

This study was performed to establish an experimental method for the investigation of interactions between ethanol and drugs under predictable and controlled conditions. The model was tested with flumazenil (Ro 15-1788), a short-acting benzodiazepine antagonist with an elimination half-life of 1 h. Six healthy volunteers (5 males, 1 female) were administered ethanol by intravenous infusion with stepwise changing rates. The infusion rates were adapted to each subject on the basis of individual disposition parameters of ethanol, which were derived from preceding short-term infusions of 120 min duration (1.0 mg/kg in males, 0.8 mg/kg in the female). This two-step procedure led to individual ethanol plasma levels between 1.47 +/- 0.04 and 1.71 +/- 0.03 g/L, which were reached after 2.5 h and thereafter maintained over another 6 h. Within the period of constant ethanol levels, single doses of flumazenil and placebo, respectively, were injected intravenously as a bolus (2 min) in a double-blind fashion according to a randomized two-way crossover design. Three subjects received a dose of 0.10 mg/kg of flumazenil, and the remaining three subjects received a dose of 0.20 mg/kg. Evaluation of the plasma concentration time curves of flumazenil did not reveal evidence of an effect of ethanol on the pharmacokinetics of this drug.

Adult↗

PubMed1988

Lack of effect of the benzodiazepine antagonist flumazenil (Ro 15-1788) on the performance of healthy subjects during experimentally induced ethanol intoxication.

Flumazenil is a specific benzodiazepine antagonist. This study was designed to determine whether it also reverses CNS depression due to acute alcohol intoxication. Intoxication was experimentally induced in 6 healthy volunteers by intravenous infusion of ethanol. Individual constant ethanol plasma concentrations in the range 1.47 +/- 0.04 g.l-1 to 1.71 +/- 0.03 g.l-1 were maintained over 6 h. Two doses of flumazenil (0.1 or 0.2 mg.kg-1) and placebo were administered intravenously in a randomized, double-blind, two-way cross-over fashion. A battery of psychometric tests and subjective ratings of mood and performance were performed at baseline and at regular intervals during the study. Before the administration of flumazenil the characteristic symptoms and signs of ethanol intoxication were present in all subjects. Performance (measured by visual analogue scales), reaction time, digit symbol substitution test, and a tracing test, were markedly impaired by ethanol. After the injection of flumazenil three volunteers reported some subjective improvement in performance. However, in none of the subjects was there a difference between either dose of flumazenil and placebo in terms of an improvement in the objective psychometric variables.

Adult↗

PubMed1988

Mechanism of action of ketanserin: studies on cardiovascular reactivity in essential and diabetes-associated hypertension.

Ketanserin is a selective serotonin-S2 receptor antagonist with alpha 1-adrenoceptor inhibiting activity. The relative contribution of the latter mechanism to antihypertensive efficacy was studied in a group comprising eight normal subjects, 10 patients with essential hypertension and eight diabetics with arterial hypertension. Ketanserin treatment administered over a period of 8 weeks, decreased arterial pressure in patients with essential hypertension and, to a lesser extent, in diabetics, but not in normal subjects. In all three groups, exchangeable sodium, blood volume, the activity of the adrenergic and renin-angiotensin-aldosterone systems and the pressor responsiveness to norepinephrine (NE) or angiotensin II (Ang II) were unaltered, while the pressor reactivity to phenylephrine showed a significant decrease in normal subjects only. This suggests that the antihypertensive mechanism of ketanserin does not involve a modification of the physiological relationship between endogenous noradrenergic and pressor reactivity to NE. Moreover, ketanserin does not interfere with Ang II-dependent mechanisms.

Adult↗

PubMed1988

Blood pressure response to tyramine-enriched meal before and during MAO-inhibition in man: influence of dosage regimen.

In an open study oral tyramine in variable doses was administered to six healthy volunteers under three different conditions: 1) without moclobemide, 2) under moclobemide steady-state conditions (3 X 200 mg moclobemide daily) one hour after moclobemide intake and 3) under moclobemide steady-state conditions simultaneously with moclobemide. It was shown that the amount of tyramine effecting 30-50 mmHg systolic blood pressure increase was roughly doubled when moclobemide was administered together with tyramine instead of one hour before tyramine intake. The time interval between tyramine ingestion and maximal blood pressure increase did not differ significantly between conditions 2) and 3). The conclusion of this study is that moclobemide should always be taken at the end of a meal, which is anyway the usual time for drug intake.

Administration, Oral↗

PubMed1988

Effect of long-term physical exercise on lymphocyte reactivity: similarity to spaceflight reactions.

The response of critical immunological parameters in seven athletes to the sustained physical stress of marathon running was assessed. Variables analysed were the responsiveness of lymphocytes (measured as mitogenic response to concanavalin A), the numbers of lymphocytes, their subsets, and leukocyte numbers. In addition, blood levels of cortisol, epinephrine, and norepinephrine were determined. After the run, lymphocyte responsiveness was severely depressed to 1-70% of the resting values, even though the lymphocyte counts did not change. Leukocyte counts were elevated 2.8-fold. No dramatic changes were found within the lymphocyte subsets, although an increase in pan T-cells and the helper/inducer subset 2 d after the run was significant. In addition, the numbers of B-cells decreased significantly. No change was observed within the suppressor/cytotoxic subset. Cortisol increased 2.1-fold, epinephrine 3.2-fold and norepinephrine 2.7-fold. All these parameters returned to baseline values within 2 d. These data were compared with data obtained during and after spaceflight. We conclude that prolonged physical stress of marathon running induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight.

Epinephrine↗

PubMed1987

Insulin-like growth factor II in human adrenal pheochromocytomas and Wilms tumors: expression at the mRNA and protein level.

Two forms of insulin-like growth factor (IGF) II with molecular masses of 10 and 7.5 kDa, respectively, were found in tumor tissue from human adrenal pheochromocytomas. The tumors contained 5.3-7.1 micrograms of immunoreactive IGF-II per g of tissue, which is about 20 times more than in adrenal medulla. The total bioactive IGF in the pheochromocytomas exceeded that in normal liver or kidney, which contained only the 7.5-kDa IGF-II species, by a factor of approximately equal to 100. By contrast, the amount of IGF-I was just measurable and did not vary significantly between tumor and normal tissue. The high amounts of IGF-II in the pheochromocytomas were not reflected, however, by a corresponding increase of mRNA. The opposite situation was found in Wilms tumors, where IGF-II content was in the same range as in nontumor tissues despite increased expression of IGF-II mRNA.

Adrenal Gland Neoplasms↗

PubMed1986

Pharmacokinetics of the new benzodiazepine antagonist Ro 15-1788 in man following intravenous and oral administration.

During clinical pharmacology studies with the benzodiazepine antagonist Ro 15-1788 the pharmacokinetic characteristics of high intravenous doses (20 and 40 mg) and of an oral dose (200 mg) were examined in six healthy male volunteers. Ro 15-1788 was rapidly and extensively distributed in the body with an apparent volume of distribution Vss of 1.06 l kg-1. Elimination occurred rapidly by hepatic metabolism and the high plasma clearance of 1.14 l min-1 resulted in a short elimination half-life of less than 1 h. No difference in the disposition parameters calculated from the data after the 20 and 40 mg doses was observed reflecting a dose-proportionality in the areas under plasma concentration-time curves and unchanged distribution characteristics. Because the blood/plasma distribution coefficient is close to unity the disposition parameters obtained from plasma concentrations are similar to the corresponding parameters with reference to blood. Following oral administration of 200 mg the drug is rapidly absorbed. Peak levels were reached after 20-90 min and were close to or even higher than the values after the 40 mg intravenous dose at the same time point. Due to the high hepatic extraction ratio the fraction reaching the systemic circulation unchanged was reduced to approximately 16% during the absorption step.

Absorption↗

PubMed1986

Adrenergic activity and aldosterone regulation: no evidence for an alpha-1 adrenoceptor-mediated influence in normal subjects.

In normal man the sympathetic nervous system could exert an inhibitory influence on aldosterone responsiveness to angiotensin II. The possible role of alpha-1 adrenoceptors in the modulation of aldosterone response was assessed by studying the changes of plasma aldosterone during infusion of angiotensin II at the doses of 1, 2, 5 and 10 ng/kg.min or after corticotrophin injection, 0.25 mg, in 9 normal subjects before and after treatment with the selective alpha-1 adrenoceptor antagonist, prazosin. Prazosin, given during 3 weeks, did not modify supine arterial pressure, heart rate and the plasma levels of angiotensin II, renin, aldosterone or adrenaline but caused a significant (P less than 0.05) increase of plasma noradrenaline. The correlation relating plasma aldosterone to plasma angiotensin II levels before and during angiotensin II infusion and the response of plasma aldosterone to corticotrophin was not modified by prazosin. These findings suggest that in normal man there is no inhibitory influence of the noradrenergic system on aldosterone responsiveness to angiotensin II mediated by an alpha-1 dependent mechanism.

Adrenocorticotropic Hormone↗