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Biomedical subjects

H Kewitz

Publications and source records attributed to H Kewitz.

At least 37 records · Page 2Linked to original sources

Rare but serious risks associated with non-narcotic analgesics: clinical experience.

Our data show that 1% of patients who required hospital treatment did so due to severe adverse reactions to analgesics. The most frequent adverse reaction was major gastrointestinal bleeding after aspirin, indomethacin, phenylbutazone or naproxen. Thrombocytopenia, second in frequency, was also mainly a complication of aspirin treatment, as was severe vertigo and tinnitus. Allergic reactions and leucopenia or agranulocytosis occurring in single cases only were associated with the use of pyrazolones. Patients with nephropathy were usually taking phenacetin or one of the close derivatives paracetamol or bucetin. Intensive monitoring for adverse reactions to drugs in 6,000 hospitalised patients in medical wards showed that analgesics, although frequently used, did not lead to life-threatening reactions. Gastrointestinal and neurological side effects were the most commonly observed reactions and these occurred more often after aspirin, indomethacin or pentazocine than after dipyrone or tilidine. Preliminary data of an international case-control-study on agranulocytosis and aplastic anaemia suggest that the incidence of agranulocytosis was in the order of 2 to 3 per million users of analgesics per year. Agranulocytosis occurred predominantly with pyrazolones, with a mortality of 1 to 2 per 10 million users per year. A cohort study on the treatment of colic pain in general practice showed that serious events most likely due to adverse reactions to analgesics were bronchospasm, shock fragments or shock. The incidence of these serious events was about 2 in 1,000 treated cases. The relative risk was not increased by treatment with pyrazolones, opioids or other drugs.

Agranulocytosis↗

Determination of thiamine in human plasma and its pharmacokinetics.

A sensitive assay for thiamine suitable for clinical use has been developed. It is based on precolumn oxidation of thiamine to thiochrome followed by HPLC-separation and fluorescence detection. The assay is applicable to various biological materials, including human plasma. The minimum amount detectable was 5 fmol, minimum plasma concentration 0.5 nmol/l and minimum sample volume 0.3 ml plasma. Each chromatographic run took 3 min. Inter- and intra-assay relative standard deviations (RSD) were 8.3% and 6.3%, respectively, at a stock plasma concentration of 10.8 nmol/l. At 38.8 nmol/l, interassay RSD was reduced to 3.4%. The recovery of 5 nmol/l added thiamine was 102 (SD +/- 17)%, that of 30 nmol/l was 94 +/- 5%. Plasma levels in 91 volunteers ranged from 6.6 to 43 nmol/l, showing a log normal distribution with a median of 11.6 nmol/l. Thiamine kinetics were studied in plasma and urine from 8 men after intravenous and oral doses of 50, 100 and 200 mg thiamine hydrochloride. In all individuals, nonlinear renal elimination kinetics were demonstrated by plotting the fractional amount of thiamine excreted unchanged in urine against the corresponding area under the plasma concentration-time curve.

Chromatography, High Pressure Liquid↗

[Metabolic effects of diuretics (author's transl)].

Thiazide diuretics and loop-diuretics, often used for treatment of hypertension, interfere with various metabolic reactions: An increase of uric acid in plasma is a regular finding, but gout will not be caused, an elevation of plasma lipoproteins has been observed but did not proceed to pathological values, in a number of patients blood glucose has been raised but without producing diabetes mellitus. In general, these metabolic interference are of minor pathological significance. Special treatment for these side-effects are needed in a few cases only. The indicated use of thiazide diuretics should not be disregarded because of their effects on regulatory mechanisms of metabolism.

Benzothiadiazines↗

Digoxin-quinidine interaction in patients with renal failure.

Investigations were performed in order to study whether or not quinidine would exert similar effects on the serum digoxin concentration in patients with renal failure as in normal subjects. Fourteen out of fifteen patients showed a significant increase of the serum digoxin level after four days of quinidine application. This indicates, that the quinidine effect is not solely caused by a decrease of the renal digoxin clearance, although nine patients, not being hemodialysed, revealed a correlation between their creatinine clearance and the rise of the serum digoxin concentration after quinidine. As however, the patients on hemodialysis did not show higher digoxin levels than those treated conservatively, it is suggested that the degree of the uremic intoxication might be responsible for the observed correlation.

Acetyldigoxins↗

Hospital admissions due to adverse drug reactions: a comparative study from Jerusalem and Berlin.

A comparative study of adverse drug reactions (ADR) leading to hostpial admission showed that 103 (4.1%) out of 2499 medical admissions in Jerusalem and 167 (5.7%) out of 2933 admissions in Berlin were due to such reactions. Sex distribution in the two patient--populations was almost equal but the Jerusalem patients were younger. The most frequent ADRs were digitalis intoxication (in Berlin) and reactions to antibiotics (in Jerusalem). Other important differences were noted in the relative frequencies of ADRs associated anticoagulants, hypoglycemic agents and oral contraceptives. They were probably related to differences in drug usage in the two countries. The most common major side effects were arrhythmias, allergic reactions, bleeding, congestive heart failure, bronchospasm and hypoglycemia. The following risk factors were identified in both cities: old age, female sex, impaired renal function, previous history of ADR and polypragmasia.

Adult↗

Reserpine and breast cancer in women in germany.

Exposure to reserpine was compared in 181 women interviewed prior to biopsy and found to have breast cancer and 307 women found to have a benign disorder of the breast. The age-adjusted relative risk of breast cancer in those who had taken reserpine was 0.6 (95% confidence limits: 0.4 and 1.1). When the 181 breast cancer patients were compared with a second control group of 101 women with a benign condition requiring surgery, the relative risk was 0.9 (95% confidence limits: 0.4 and 1.7). Neither long-term exposure nor its timing, gave any evidence of an association with breast cancer. The findings in this study do not support the hypothesis that rauwolfia derivatives initiate or promote breast cancer.

Adult↗

Inhibition of choline incorporation into brain lipids in rats by urethane, a proposed mechanism of depression of the central nervous system.

Concentrations and specific radioactivities of choline, acetylcholine, phosphorylcholine, lipid choline, and sn-glycero-3-phosphorylcholine after i.v. injection of methyl-14C-choline were measured in the brain of untreated controls and of rats anesthesized with urethane. The specific activity was found to be decreased during deep anesthesia by 40% in acetylcholine, 20-30% in phosphorylcholine, 50-75% in lipid choline, and 30-40% in sn-glycero-3-phosphoryl-choline. No significant change was detected in the specific activity of choline. The brain concentration of acetylcholine was increased by 40%, the concentration of sn-glycero-3-phosphorylcholine, however, was diminished by 10% during anesthesia. No change was found in the concentration of the other choline containing compounds investigated. Measuring choline incorporation into 4 subcellular fractions of brain tissue specific activities were found to be decreased by the same percentage, although 2 fractions (nuclei and microsomes) were higher labelled than the 2 other fractions (crude mitochondria with synaptosomes and lysosomes). A correlation between the biochemical and the functional alterations is supported by the dose-effect relationships on both parameters. It is suggested that urethane reduces turnover of lipids and by that mechanism inhibits the exocytotic release of the transmitter from presynaptic nerve endings.

Animals↗

Mechanism of the enrichment of phosphatidylcholine in liver accompanying enzyme induction by phenobarbital.

The mechanism of the increase of phosphatidylcholine in liver, accompanying enzyme induction by phenobarbital, has been studied in rats. Using radioactively labeled precursors, the two main pathways of phosphatidylcholine biosynthesis--the CDP-choline pathway and the methylation of phosphatidylethanolamine--were analyzed after pretreatment with 4 doses of phenobarbital (80 mg/kg) on 3 consecutive days. After i.v. injection of choline [Me-3H], choline [Me-14C] or NaH2[32P]O4 the specific radioactivity (sp. act.) of phosphatidylcholine (dpm/nmol) was decreased by 60%, and after methionine [Me-3H] or ethanolamine [1.2-14C] by 40% compared to control rats. These changes are partly due to the increased concentration of phosphatidylcholine and phosphatidylethanolamine, causing the incorporated precursors to dilute, and partly to a secondary effect which leads to a reduction of the sp. act. of free choline in pretreated animals. The concentration of glycerylphosphorylcholine, one of the metabolites of phosphatidylcholine catabolism, was also diminished by almost 50%. From these results it may be concluded that the increase of phosphatidylcholine is due to a retardation of its breakdown rather than to an increase of its synthesis.

Animals↗

Synthesis of choline from ethanolamine in rat brain.

Specific radioactivities of choline, acetylcholine, phosphocholine, lecithin, lysolecithin, and glycerophosphorylcholine have been measured in brain, blood, liver, and muscle after the intravenous injection of three labeled precursors: choline, methyl-labeled methionine, and ethanolamine. In relation to the specific activity of free choline in blood there was significantly more radioactivity in the free choline of brain after administration of methyl-labeled methionine and labeled ethanolamine than after labeled choline. Since the choline moiety of lipids, which returns back to the choline pool, contained less radioactivity after methyl-labeled methionine and labeled ethanolamine than after labeled choline, it is the most likely interpretation of the finding that choline, in brain can be formed by methylation of free ethanolamine. Data from liver confirm that lecithin is formed in the liver by methylation of phosphatidylethanolamine. No indication was found for the synthesis of choline in muscle. Rates of transfer and transport of choline in brain have been calculated as nmol x g-1 x min-1 as follows: turnover rate of choline, 36.5; rate of synthesis of choline by methylation and net loss of choline into the bloodstream, 6.3; inflow from the blood 6.2; outflow into the blood, 12.5; transfer into lipids and vice versa, 20; transfer to acetylcholine and vice versa, 4.

Acetylcholine↗

[One hundred years pilocarpine in ophthalmology (author's transl)].

In 1876 A. Weber introduced chemically from P. jaborandi isolated Pilocarpium muriaticum into the ophthalmological therapy. One year later it was used as a local drug to lower the intraocular pressure in glaucoma and replaced in the following years the extract of Calabar bean (Eserine). Clinical and pharmacological data are discussed.

Germany↗

Evaluation of in vivo parameters of drug metabolizing enzyme activity in man after administration of clemastine, phenobarbital or placebo.

The 24 h urinary excretion of 6beta-hydroxycortisol and D-glucaric acid, the plasma half lives and total clearances of aminopyrine, and serum gamma-glutamyl-transpeptidase activity have been measured in nineteen healthy male volunteers. The study was done double blind and was conducted as a test of induction of microsomal drug metabolizing enzymes during and after daily doses of 6 mg clemastine, 300 mg phenobarbital or a placebo. The urinary excretion of 6beta-hydroxycortisol and D-glucaric acid was significantly increased in the phenobarbital group, the standard for induction. No changes were observed after treatment with clemastine or placebo. Phenobarbital also reduced the half life of aminopyrine, but it was not affected by clemastine or placebo. Gamma-glutamyl-transpeptidase activity increased only in the phenobarbital group. The elimination constant k2 of aminopyrine and the excretion of glucaric acid in the pre-medication period were correlated (p less than 0.05) The results indicate that the tests were of diagnostic value in determination of microsomal enzyme induction by phenobarbital. Failure to observe similar changes after treatment with clemastine imply failure of induction of this activity under the experimental conditions.

17-Hydroxycorticosteroids↗