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Biomedical subjects

R Zimmer

Publications and source records attributed to R Zimmer.

At least 55 records · Page 3Linked to original sources
PubMed1990

Potentiation of the pressor effect of intravenously administered tyramine during moclobemide treatment.

Potentiation of the pressor effect of tyramine (TYR) by intravenous (i.v.) injection during moclobemide treatment was investigated in healthy volunteers and in depressed patients. The TYR sensitivity factor (TSF) is calculated as the ratio between the dose of TYR required to raise systolic blood pressure by 30 mmHg (TYR 30) without drug and that required with drug. After single-dose administration the TYR 30 for 100 mg moclobemide was 1.8 mg, and those for moclobemide 200 and 300 mg 1.6, compared with 3.2 for placebo, giving corresponding TSF values of 1.7, 2.0 and 2.0 respectively. Twenty-four hours after moclobemide intake, only the 300-mg dose yielded a mean TYR 30 value significantly different from placebo. The same doses of moclobemide given 3 times daily for 1 week resulted in a peak TSF of 2.0 with 100 mg, 2.9 with 200 mg and 3.3 with 300 mg (the latter dose being higher than normally recommended for 3 times daily administration). Nevertheless, 24 h after the last 300-mg dose the TSF was 1.2, similar to that of a single dose. In a study of 17 depressed female patients treated with moclobemide 100 mg 3 times daily, no relevant differences were found in TSF values from those of the volunteers. The authors conclude that, because of the short-lasting, reversible and selective MAO-A-inhibiting effect of moclobemide, there is no marked interaction with tyramine given by i.v. injection. No relevant difference was seen between depressed patients and healthy volunteers in the tyramine pressor effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents↗
PubMed1990

Interaction between orally administered tyramine and moclobemide.

This article describes a standardized oral tyramine pressor test designed to give information on safety aspects in the real everyday life situation where tyramine is ingested only with food. Results showed that significantly higher doses of tyramine were required to raise standing blood pressure by at least 30 mmHg (TYR 30) when it was taken with food than when subjects fasted. The same test was then conducted in 8 healthy volunteers during treatment with moclobemide 200 mg 3 times daily and tranylcypromine 10 mg 3 times daily. With moclobemide the mean TYR 30 dose was 306 mg, and the ratio of this to baseline was 5.0. With tranylcypromine, however, the mean TYR 30 dose was only 35 mg and the TSF ratio 38.2. The potentiation by tranylcypromine was thus 7.6 times greater than that of moclobemide. When tyramine was given in the food under treatment with MAO inhibitors, the TYR 30 doses were larger than those obtained under fasting conditions, but the TSF ratios were not altered. When the tyramine was given in a protein-rich or a lipid-rich meal, the previously established TYR 30 had significantly less effect on the blood pressure. The lowest TYR 30 dose during moclobemide treatment is at least 150 mg tyramine, an amount contained in about 300 g strong cheese or 100 g of yeast extract. These quantities are unlikely to be consumed in a normal meal. The corresponding TYR 30 dose for tranylcypromine, however, is only 20 mg tyramine, which can easily be contained in a fairly normal portion of strong cheese (40 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Relationship between tyramine potentiation and monoamine oxidase (MAO) inhibition: comparison between moclobemide and other MAO inhibitors.

The pharmacodynamic properties of moclobemide, a reversible inhibitor of MAO-A (RIMA), were compared with the properties of other reversible as well as older irreversible MAO inhibitors in human subjects. All the substances supposed to have MAO-A-inhibitory activity, with the exception of toloxatone, were shown by the decrease in plasma DHPG or MHPG levels to cause inhibition ranging between 50% and 85%. Toloxatone and low doses of deprenyl (a MAO-B inhibitor) caused 20% and 17% inhibition respectively; higher doses of deprenyl, however, strongly inhibited MAO-A. MAO-B inhibition was confirmed for all nonselective and selective MAO-B inhibitors. Moclobemide and clorgyline were found to be the most highly selective MAO-A inhibitors, although both also inhibited 30% of platelet MAO-B activity. Potentiation of the tyramine pressor effect is mainly influenced by the irreversibility and degree of MAO-A inhibition. Tyramine sensitivity was raised (a factor of 10-30) by all irreversible MAO inhibitors in doses inhibiting MAO-A; it diminished with increasing reversibility. In therapeutic doses, moclobemide potentiated the intravenous tyramine pressor effect 3 times less than the old irreversible MAO inhibitors; with the highest therapeutic dose, the tyramine sensitivity factor for moclobemide is only one-seventh to one-tenth that of tranylcypromine or phenelzine. Duration of action is obviously also closely related to the reversibility of inhibition: it ranged from up to 2 days with high doses of moclobemide to 3 weeks with tranylcypromine; clorgyline and phenelzine have been shown to maintain their action for several months. The new generation of RIMAs represents a significant progress in safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents↗
PubMed1990

Interaction studies with moclobemide.

Drug interactions with moclobemide given to healthy subjects and depressed patients are reviewed. The drugs investigated for safety were antihypertensives, digoxin, oral contraceptives, anticoagulants and benzodiazepines. Cimetidine was studied for the pharmacokinetic effect, and possible interactions with alcohol (stimulation and/or sedation) were included. Finally, since inhibition of monoamine oxidase (MAO) can increase noradrenergic transmission, possible interaction with neuronal reuptake inhibitors such as tricyclic antidepressants (TCAs) was investigated. Whereas replacement of the older, irreversible MAO inhibitors by a TCA was held to be dangerous and to require a therapy-free interval, the studies reviewed here provide evidence that amitriptyline can replace or be added to moclobemide without any sign of impaired tolerance, need for dose reduction or a therapy-free interval. Combined administration of moclobemide and desipramine was also tolerated well. Moclobemide did not interact with the direct-interacting sympathomimetics norepinephrine and isoproterenol and only to a negligible extent with phenylephrine. The combination of moclobemide with antihypertensive agents did not cause postural hypotension or an increase in other side effects. No clinically relevant interaction was observed between moclobemide and phenprocoumon, glibenclamide, oral contraceptives, digoxin or benzodiazepines. Cimetidine increased the concentration of moclobemide in plasma after a single oral dose by about 100%. If moclobemide is to be used in a patient pretreated with cimetidine, treatment should therefore start with the lowest therapeutic dose and then be adjusted to clinical needs. Since moclobemide is devoid of anticholinergic effects, no interaction with alcohol was anticipated. High therapeutic doses (600 mg/day) induced an effect similar to that of low doses of a TCA, but with 100-300 mg no interaction with alcohol was seen, even in elderly people.

Antidepressive Agents↗
PubMed1989

Determination and comparison of the pressor effect of tyramine during long-term moclobemide and tranylcypromine treatment in healthy volunteers.

Monoamine oxidase inhibitors can elicit increases in systolic blood pressure after tyramine ingestion (cheese effect). Moclobemide is a new, reversible, preferential monoamine oxidase A inhibitor with antidepressant properties. Its potentiation of the tyramine pressor effect during 200 mg t.i.d. chronic treatment was compared with tranylcypromine, 10 mg b.i.d., in a double-blind, parallel-group, placebo-controlled study (n = 16). Tyramine was mixed with food and ingested in increasing daily doses, during a normal meal, until a systolic blood pressure increase of at least 30 mm Hg was achieved (tyramine 30). When compared with the usual fasting oral tyramine tests performed in the same subjects, the mean tyramine 30 dose with a meal was 2.8 times higher. The mean tyramine 30 dose with a meal decreased from 1450 mg (range, 800 to 2000 mg) during placebo to 306 mg (range, 150 to 500 mg) during moclobemide (factor, 5.0) and from 1200 mg (range, 1000 to 1600 mg) during placebo to 35 mg (range, 20 to 50 mg) during tranylcypromine (factor, 38.2). The duration of the systolic blood pressure increase was longer with tranylcypromine (126 minutes) than with moclobemide (69 minutes) (p less than 0.01).

Administration, Oral↗
PubMed1988

[Dementia].

This report briefly reviews the clinical diagnosis of dementia, including the most important problems of differential diagnosis. General guidelines of therapy are presented with special reference to the modification of secondary factor which may contribute to the severity of dementia and to psychosocial approaches in the management of patients.

Aged↗
PubMed1988

Diagnosis, differential diagnosis and nosologic classification of the dementia syndrome.

Some clinical aspects of the diagnosis, differential diagnosis, and the nosologic classification of the dementia syndrome are presented. In discussing the definition of the dementia syndrome and its differentation from other organic brain syndromes, the criteria of DSM III are taken into account. Considering the nosological classification of the dementia syndrome particular emphasis is placed on the most frequent diseases in the senium, the Multi-Infarct Dementias (MID) and the primary degenerative dementias (PDD, according to DSM III). The clinical problems in differentiating MID from PDD and Morbus Pick from the dementia of the Alzheimer type in the group of are discussed in more detail.

Aged↗
PubMed1988

Sodium-lithium exchange in sarcolemmal vesicles from canine superior mesenteric artery.

Exchange of intracellular sodium for extracellular lithium readily occurs in vascular smooth muscle, but the mechanism of this exchange is not known. These studies examined whether a sodium-lithium countertransport system was present in the cell membrane of vascular smooth muscle. A sarcolemmal-enriched vesicle preparation was obtained from canine superior mesenteric artery via a magnesium aggregation and differential centrifugation technique. An outwardly directed gradient for lithium stimulated 22Na uptake by the vesicles, and an inwardly directed gradient for lithium stimulated 22Na efflux. These effects were not due to an alteration in membrane potential, and sodium uptake was not stimulated by lithium in the absence of a gradient for lithium. The lithium gradient-stimulated component of sodium uptake was not affected by a change in membrane potential and was insensitive to ouabain. Both sodium-lithium exchange and sodium-proton exchange in sarcolemmal-enriched vesicles were inhibited by two compounds that inhibit the sodium-lithium countertransport system in red cells, phloretin and quinidine. Ethylisopropylamiloride also inhibited both sodium-lithium exchange and sodium-proton exchange in the vesicles. In support of the possibility that sarcolemmal sodium-lithium exchange and sodium-proton exchange are mediated by a single cation exchange mechanism with affinity for sodium, lithium, and protons, we found that an inwardly directed sodium or lithium gradient stimulated proton efflux, and that the stimulation of sodium efflux by external lithium or protons was not additive. It is concluded from these studies that sarcolemmal vesicles from canine superior mesenteric artery contain an electroneutral, phloretin, quinidine, and ethylisopropylamiloride inhibitable sodium-lithium exchange transport system.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1986

An endoscopic micromanipulator for multiplanar transesophageal imaging.

We have developed an esophageal probe with a precision micromanipulator and a transversely oriented 32 element ultrasonic array which operates at 3.5 MHz. The probe allows us to obtain multiple two-dimensional images of the heart with known angular relationships between them over a series of cardiac cycles. Our ultimate purpose is to acquire images for left ventricular volume estimation with a three-dimensional reconstruction method. Technical details of the probe design are given. In vitro tests have shown that the imaging plane can be angulated within 1.5 degree root mean square error. In vivo results with dogs have demonstrated its ability to obtain multiplanar short axis images of the heart.

Animals↗
PubMed1984

Gamma-aminobutyric acid and homovanillic acid concentration in the CSF of patients with senile dementia of Alzheimer's type.

The investigation of enzyme and neurotransmitter levels and/or their metabolites in the CSF of patients with senile dementia of Alzheimer's type (SDAT) could become a promising approach for a clinical research and diagnostic procedure. To learn more about the metabolic reflections of central metabolism in the CSF of patients with SDAT, we measured CSF levels of gamma-aminobutyric acid (GABA) and homovanillic acid (HVA), the dopamine metabolite. In 16 female patients with SDAT and in eight matched control patients, CSF GABA levels were measured by ion exchange with fluorimetric detection, and HVA levels were measured fluorimetrically. The GABA content of the CSF was significantly reduced in patients with SDAT, whereas the HVA level was unchanged.

Aged↗
PubMed1984

[Evaluation of plasma tumor markers in germinal tumors of the testis].

Pregnancy specific beta 1 glycoprotein (PS beta 1G), human choriogonadotropin (hCG), alpha-foetoprotein (AFP) and carcinoembryonic antigen (CEA) were measured simultaneously in 58 patients with a progressive germinal testicular tumour, and in 20 patients in complete remission. All markers were negative in all the cases in remission, and in 1 case of progressive teratoma. The specificity of the association of these 4 markers was 76 p. 100, higher than any of them measured alone. There was no correlation between individual markers with respect to histological classification. The highest diagnostic specificity was obtained with hCG in all types of tumours. PS beta 1G was associated with hCG but with a lower specificity. AFP is mainly related to embryonic carcinoma but may be raised in all forms of tumour, except seminomas. CEA was positive less often, irrespective of the type of tumour, and never alone. The value of measuring these tumour markers is double: on the one hand it allows better characterisation of the tumour, and on the other, the clinical course and efficacy of treatment can be followed-up more closely and tumour recurrence may be diagnosed at an early stage.

Carcinoembryonic Antigen↗
PubMed1982

Changes in cerebrospinal fluid cyclic nucleotides in alcohol-dependent patients suffering from delirium tremens.

In eight patients with a history of alcoholism (on average 9 years), cyclic 3',5'-monophosphate (AMP) and cyclic 3',5'-monophosphate (GMP) were determined in CSF in the acute untreated phase of delirium tremens and at 2 weeks later when clinical symptoms had vanished. Before the second lumbar puncture a drug-free period of 1 week had existed. The results were compared with an age- and sex-matched neurological control group. CSF cyclic AMP concentrations were markedly reduced by 62% (p less than 0.005) in the acute state of delirium tremens and remained at the same level 2 weeks later; cyclic GMP concentrations were increased by 37% (p = 0.05) and showed a small further increase (p less than 0.05) at the second lumbar puncture. A negative correlation existed between age and cyclic AMP content of CSF (r = -0.756; p less than 0.05) in the patients group. The data indicate that the earlier observed increase in norepinephrine turnover in the acute state of delirium tremens (Athen et al., 1977) seems not to induce an increase of cyclic AMP content in CSF.

Adult↗
PubMed1981

[An ethological interpretation of stereotypy induced by environmental stimulus (author's transl)].

Stereotyped behavior in the schizophrenic patient is described, provoked by yawning or fragments of this act in the environment. It consists of elements that, in an ethological sense are reminiscent of activities which increase vigilance and cleanse the body. It is suggested that yawning brings about a certain 'mood transfer' which induces this kind of specific stereotyped behavior. The adequacy of an ethological interpretation of these symptoms of disease is briefly discussed.

Adolescent↗