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Biomedical subjects

G Metz

Publications and source records attributed to G Metz.

At least 37 records · Page 2Linked to original sources
PubMed1987

Calmodulin antagonism: a pharmacological approach for the inhibition of mediator release from mast cells.

Several Ca2+ antagonists with either Ca2+-entry blocking or calmodulin (CaM) antagonistic properties and antiallergic drugs were investigated for their effects on mediator release from mast cells induced by different secretagogues (compound 48/80, concanavalin A, antigen-IgE and Ca2+ ionophore A23187) and for their ability to inhibit the function of CaM or phospholipid/Ca2+-dependent protein kinase (C-kinase). The effects of the different agents--with the only exception of cromolyn sodium--on histamine release elicited by compound 48/80 correlated well with their actions on two CaM-dependent enzymes whereas the activity of C-kinase was far less altered, or not altered at all. CaM antagonism of cloxacepride, picumast, oxatomide, fendiline and bepridil correlated not only with the inhibition of exocytosis evoked by compound 48/80 but also with that induced by A23187, concanavalin A and antigen-IgE. This indicates an action of these substances distal to the generation of the Ca2+ signal since the various secretagogues elevate the intracellular Ca2+ concentration by different mechanisms. However, prenylamine and thioridazine inhibited concanavalin A- and antigen-IgE-induced mediator release more potently and more effectively than that elicited by compound 48/80 or A23187. Therefore inhibition of allergic histamine release by these drugs may in part be dependent on an impairment of the Ca2+ signal. Since for each of two agents inhibition of histamine release (evoked by different releasers) parallels that of serotonin release it may be concluded that these mediators are secreted via the same mechanism. The results obtained with agents exhibiting different pharmacological properties but which share one common property, namely antagonism of CaM, strengthen the view that CaM is involved in exocytosis of mediators from mast cells.

Animals↗
PubMed1986

Failure of ibuprofen in treatment of herpes genitalis.

Motrin (ibuprofen), a potent inhibitor of prostaglandin synthetase, was tested in women and men for treatment of recurrences of genital herpes. In a double-blind trial, no statistically significant differences were observed between treated and placebo groups in any of the measured parameters.

Adult↗
PubMed1986

Effect of etofylline clofibrate on experimental thrombus formation and prostacyclin activation.

1-(7-Theophyllinyl)-2-ethyl-[2-(p-chlorophenoxy)-isobutyrate] (etofylline clofibrate, theofibrate, Duolip) was shown to possess substantial thrombus disaggregating activity in the microcirculation of the hamster cheek pouch following minor vascular damage by electrical stimulation. At 12 mg/kg p.o. the moderate effect of a single dose (12% reduction in disaggregation time) increased to a maximum reduction of 31 and 43% following 5 and 7 consecutive daily applications, respectively. Etofylline clofibrate was more active than other drugs already tested in this test system, but less than the prostaglandins PGE1 and PGI2. The antithrombotic efficacy found in both in vivo tests, thrombus formation and disaggregation, suggests as mode of action of etofylline clofibrate an agonistic interaction with intimal PGI2. This could be by enhancement of its production or by a synergistic interaction with this prostanoid, rather than inhibition of thromboxane A2 synthetase.

Animals↗
PubMed1985

Blood transfusion requirements in coronary artery surgery with and without the activated clotting time (ACT) technique.

Control of anticoagulation during cardiopulmonary bypass (CPB) with the automated activated whole blood clotting time (ACT) and reversal of heparin after CPB using a computerized ACT dose-response curve method resulted in significant reductions of blood transfusion requirements, surgical time, and protamine doses in 150 patients undergoing coronary artery bypass grafting procedures (ACT group) as compared to 200 patients for whom a standard fixed dose protocol for heparin and protamine was used (control patients). Mean transfusion requirements were 1,938 +/- 60 SEM ml whole blood and 853 +/- 48.3 SEM ml red blood cells for control patients and 1,397 +/- 59 SEM ml whole blood (P less than 0.001) and 695 +/- 34 SEM ml red blood cells (P less than 0.01) in the ACT group. ACT group patients also required less protamine with 26.2 +/- 0.60 SEM ml Protamine 1,000 (Roche) as compared to 33.9 +/- 0.49 SEM ml for control patients (P less than 0.001) but more heparin with 31,440 +/- 783 SEM I.U. versus 26,760 +/- 263 SEM I.U. (P less than 0.001). Surgical time decreased from 321 +/- 5.5 SEM min for control patients to 289 +/- 5.4 SEM min for ACT group patients (P less than 0.001).

Blood Coagulation Tests↗
PubMed1984

Methods of introducing nasoenteric feeding. A prospective randomized study.

In 50 patients requiring enteral nutritional support, a nasogastric feeding regimen with an isotonic, polymeric solution was introduced either by the slow, conventional four-day method or by a more rapid one. The incidences of symptoms associated with either introduction protocol were compared. As many as 82% of patients showed no sign of intolerance, whatever the method used. Of the remainder, four developed symptoms that might have been associated with the treatment. Only one of these patients had been subjected to the fast introduction protocol. It is concluded that undiluted isotonic lactose-free nasoenteric solutions can be safely introduced rapidly to meet energy requirements earlier.

Enteral Nutrition↗
PubMed1984

Similarities between human and rat leukocyte elastase and cathepsin G.

Rat is a likely test animal for determining the efficacy of proteinase inhibitor drugs directed toward human leukocyte elastase and cathepsin G. We therefore sought to assess and compare relevant properties of both human and rat leukocyte elastase and cathepsin G. Some differences between the pairs of proteinases from the two species were found, however both pairs of enzymes displayed comparable specificity toward various natural (plant and animal) proteinase inhibitors and also toward specific peptide substrates and a serine proteinase-specific reagent. Such overlapping specificity implies similarity of reactive center topography and sequence homology around the extended substrate/inhibitor binding regions of these proteinases. This apparent homology leads us to conclude that a pharmacologically effective inhibitor of leukocyte proteinases in the rat would probably also be effective in man.

Aniline Compounds↗
PubMed1984

Inhibitory effect of cloxacepride on compound 48/80-induced histamine and serotonin release from rat mast cells.

Cloxacepride, a potent inhibitor of passive cutaneous anaphylaxis (PCA) in the rat, was evaluated for in vitro inhibitory effect on 48/80-induced histamine and serotonin release from rat mesenterial mast cells. Significant inhibition and linearity of concentration and effect was found in the concentration range of 10 to 50 microM. The IC50 was determined to 21 microM (histamine) and 19 microM (serotonin). A simultaneous liberation of both mediators from mast cells is indicated from nearly identical IC50. LDH increase in the supernatant of the incubation mixture by cell damage resulted from higher concentrations of cloxacepride (greater than 50 microM). The high concentration of 10 micrograms/ml releaser 48/80 did not affect or diminish the effect of cloxacepride, while the reference compounds cromolyn sodium (DSCG) and theophylline were inactive under these conditions. The substantial inhibition of the PCA reaction and of the mediator release from mast cells provides cloxacepride a promising potential antiallergic drug.

Animals↗
PubMed1984

[An electronic communication aid with a large keyboard for artificial respiration patients in the intensive care unit].

An increasing number of patients under mechanical ventilation in ICUs suffers from being cut off from normal communication. The existing communication facilities, such as letter-boards, magnetic letters, pictograms, Yes-no-signals and attempts at written communication are very often insufficient or not to be mastered by the weakened ICU respirator patient. We, therefore, present an electronic communicator consisting of a keyboard with big push-buttons and an illuminated running-letter display. Up to one page of text can be stored in memory and recalled later as running or printed text. Initial experiences with the electronic communicator show that even weakened respirator patients with diminished sensomotoric abilities successfully manage to communicate with the staff.

Communication Devices for People with Disabilities↗
PubMed1983

Abdominal blood pool scintigraphy in the management of acute or intermittent gastrointestinal bleeding.

Gastrointestinal blood pool scintigraphy, using a modified in-vivo red blood cell labelling technique with technetium-99, is a new, easily performed, non-invasive procedure. It is valuable in screening patients with acute or intermittent gastrointestinal blood loss in whom duodenoscopic and sigmoidoscopic findings are unhelpful. This paper reviews the value of this scintigraphic technique over the first eight months of its use in a major teaching hospital, and compares the results with other published data. The high sensitivity of this procedure, and its ability to demonstrate gastrointestinal bleeding very strikingly, are illustrated with several examples. If used and interpreted appropriately, scintigraphy is sensitive in detecting and localizing the bleeding site, and is very helpful in indicating the optimal timing of emergency contrast angiography. The study further supports the view that scintigraphy should be the initial diagnostic imaging procedure in this group of patients, and that emergency angiography should be reserved primarily for patients in whom there is scintigraphic evidence of continuing blood loss.

Abdomen↗
PubMed1983

Cloxacepride and related compounds: a new series of orally active antiallergic compounds.

4-[[(p-Chlorophenoxy)acetyl]amino]-5-chloro-2-methoxy-N-[2-(diethylamino)ethyl]benzamide (cloxacepride, 1), exhibited substantial oral antiallergic potential in a reaginic PCA test in rats over a wide range of antigenic challenge times. Available reference compounds with oral activity, such as doxantrazole and 7-(2-hydroxyethoxy)-9-oxoxanthene-2-carboxylic acid (AH 7725, 4), were active only when administered 15 min before challenge: 4, in particular, was not consistent in effect. Oral ED50 values for cloxacepride of 46-49 mg/kg were comparable to that of theophylline and to an intravenous injection of 2 mg/kg of disodium chromoglycate (DSCG) followed by immediate challenge. Following oral ED50 doses, 1 showed slower onset and longer duration of action than theophylline. The absence of inhibition of systemic anaphylaxis and of antihistaminic activity suggests specific effect or reaginic antigen antibody reactions. Structure-activity relationships of various chemical modifications were investigated and discussed in terms of essential substituents.

Administration, Oral↗
PubMed1981

Pectin in the dumping syndrome: reduction of symptoms and plasma volume changes.

Twelve patients with the dumping syndrome took on one occasion oral hypertonic glucose and on another a similar glucose drink to which pectin was added. After glucose alone eleven patients had symptoms; after glucose with pectin, six had no symptoms and in five symptoms were reduced. Plasma volume changes were significantly less after glucose with pectin, and the hypoglycaemia at 120 min after glucose alone did not occur after glucose with pectin in patients in whom symptoms were abolished. Gastric emptying was prolonged, and serum insulin levels were lower, after glucose with pectin. In those patients to whom gastric emptying rate reverted to near normal with pectin, symptoms were abolished, but symptoms were only reduced in number when gastric emptying, although slowed, remained rapid. The findings suggest that pectin and similar substances may be useful in the day-to-day management of patients with dumping symptoms.

Adult↗
PubMed1981

[Pyoderma gangrenosum (dermatitis ulcerosa)].

Even though pyoderma gangrenosum (dermatitis ulcerosa) is still considered to be a polyetiological syndrome with uncertain pathogenesis, immunological processes are attributed to it. It serves as an indicator of an underlying internal disease. A more than incidental occurrence is found of inflammatory intestinal diseases such as colitis ulcerosa, inflammatory joint disorders, among hematological diseases predominantly myeloic leukemia, paraproteinemia with and without plasmocytoma as well as inflammatory vascular processes. A variety of other simultaneous diseases have to be considered as isolated case reports; it remains for future investigations to decide if these will be classified among the merely coincidental diseases or as various manifestations of a common immunological process.

Anti-Bacterial Agents↗
PubMed1981

Effect of hypolipidaemic drugs on hepatomegaly and micro-bodies in the rat. A new approach to the nature of hepatic peroxisomal proliferation.

Etofylline clofibrate, a new hypolipidaemic drug of low toxicity, was evaluated for effects of induction of peroxisomal proliferation and hepatomegaly in male rats by comparison with standard hypolipidaemic drugs (bezafibrate, clofibrate, fenofibrate). The dose schedule was selected according to standard toxicological methods in an attempt to determine a dose-dependent relationship with particular reference to a possible "nil effect" dose. At high dose levels (250 mg/kg/day), all test drugs induced proliferation and hepatomegaly. At 50 mg/kg/day, all reference compounds induced proliferation and hepatomegaly while etofylline clofibrate indicated only moderate proliferation and no hepatomegaly. At very low dose levels only standards induced proliferation while etofylline clofibrate neither induced proliferation nor hepatomegaly. The latter was still present in bezafibrate and fenofibrate-treated groups. Results indicated a dose-dependent effect of etofylline clofibrate on both parameters with a "nil effect" dose between 11 and 50 mg/kg. Neither a dose-dependent nor a "nil effect" dose was found with any of the standard drugs. For the most potent peroxisomal proliferators (bezafibrate and clofibrate), numerous large and mis-shapen peroxisomes were found at all dose levels. Hepatic changes in terms of pharmacological and toxicological criteria are discussed with special reference to a proposed drug related toxic effect on liver function.

Animals↗