[Internal processing of iodate].
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Biomedical subjects
Publications and source records attributed to H Hoffmann.
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The antihypertensive activity of two fixed beta-blocker combinations was compared in a randomized double-blind study. 18 patients with degree I or II hypertension and hyperuricaemia were treated with a once daily dose for 4 weeks. 9 patients received 200 mg celiprolol. HCl +25 mg chlorthalidone, and 9 patients were treated with 100 mg atenolol + 25 mg chlorthalidone. Both substances produced a similar reduction in blood pressure and heart rate. There was a significant rise in the serum uric acid level in both treatment groups.
Metastatic adenocarcinoma without demonstration of the primary tumour was diagnosed within a period of 42 months in 13 women and 11 men, median age 68.5 years. Analysis of initial symptoms, cardinal findings on first examination and pathological laboratory values pointed predominantly to a primary site in the abdomen. The following conclusions were drawn from this study, with all the disadvantages of retrospective analysis: in a majority of patients (14) the tumour mass could be localized in the upper abdomen. Primary sites include pancreas, biliary tract and gallbladder and possibly colon in the differential diagnosis. There is usually not a good response to chemotherapy. On the other hand, it is important to examine all organs for possible primary site of a carcinoma the metastases of which can be successfully treated by chemotherapy or hormones (mammary, ovarian, testicular, thyroid and prostate carcinoma). Taking into account a median survival time of 28 weeks and the fact that 73% of all technical investigations were normal, diagnostic measures should be as few as possible, restricted predominantly to clinical and biochemical ones, radiography of the thorax, abdominal ultrasound, digital pelvic examination, mammography, and serological and cytological tumour parameters.
The influence of two differently constructed dose schedules and of two dissimilar administration routes on the subacute toxicity of the potential antiviral drug benzoxazolyl-2-formyl-S-ethyl-isothiosemicarbazone was investigated in mice. Administration of identical aliquots of the, route dependent, maximally tolerated, dose was found to cause no significant differences in weight gain in any of the schedules used, but marked changes in lethality after oral or subcutaneous administration could be demonstrated.
44 patients with advanced squamous cell carcinoma of the head and neck were randomized and treated preoperatively either with arm "A": cis-DDP (3 mg/kg iv day 1) and BLM (15-20 mg iv continuously day 2-6) or arm "B": MTX (30 mg/m2 iv day 1 + 6) and VDS (3 mg/m2 iv day 2 + 7). Treatment with arm "A" was superior producing 73% complete and partial remissions (CR + PR) compared to 40% for arm "B" (p = 0,05). The number of patients with CR could be increased from 2 to 26 by surgery and/or radiotherapy. The median survival for patients with chemotherapeutically induced CR and PR was 16 months but this did not differ significantly from the median survival (13 months) of non responders (p = 0.25). For patients with CR and PR achieved by surgery and/or x-ray therapy the median survival point has not yet been reached, and this is significant compared to the non responders (p = 0.001). Five of 26 patients with CR died after 39 months of observation and 6 are living with recurrence. In addition to clinical trials, chemotherapy is indicated for patients with inoperable tumours. The value of chemotherapy can only be answered by randomized trials comparing chemotherapy combined with standard procedures against surgery and radiotherapy alone.
First order rate constants of the hydrolysis of N-[(1-allyl-2-pyrrolidinyl)-methyl]-6-methoxy-1H-benzotriazole-5-carboxa mide (alizapride, Vergentan) in acid and alkaline medium were determined. The activation energy observed in alkaline solution was 60.3 kJ X mol-1. The substance was not hydrolized in vitro by esterase, liver homogenate and plasma.
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A total of 437 acute psychiatric inpatients were investigated with the help of a questionnaire containing DSM-III diagnostic criteria for schizotypal as well as for borderline personality disorder and criteria of the Flexible System for the diagnosis of schizophrenia. All patients were also independently diagnosed according to the ICD-9. The clinical ICD-9 diagnoses were compared with the diagnoses given on the basis of the three operational criteria sets mentioned. Patients fulfilling the operational criteria for schizotypal personality disorder were clinically diagnosed as mostly schizophrenic, and there was also a considerable overlap between the two groups of patients, those fulfilling the operational criteria for schizotypal personality disorder and those fulfilling the criteria of the Flexible System for the diagnosis of schizophrenia. Schizotypal personality disorder does not seem to be a clinical entity in the sense of a traditional personality disorder. The majority of patients diagnosed as borderline personality disorder received a clinical diagnosis of a personality disorder. The DSM-III criteria of borderline personality disorder discriminated satisfactorily against schizophrenia as diagnosed by the Flexible System and as diagnosed according to ICD-9. On the other hand, there was no relationship between the borderline personality disorder diagnosis and any single of the ICD-9 personality disorder types. The patients fulfilling the criteria of the borderline personality disorder were equally distributed across all ICD-9 personality disorder types. They were also significantly younger than both the non-borderline and the ICD-9 personality disorder patients. The relationship between borderline personality disorder criteria and age might thus be of a greater relevance than the relationship between these criteria and a clinical type.
The heat-induced formation of lysinoalanine (LAL) was studied in raw skim milk that had been subjected to heat treatments as is usual in milk technology. Preheat treatment of milk at temperatures below 100 degrees C up to 20 min resulted in neglectable LAL amounts below 10 ppm i.p. (i.p.=in the protein) if at all. Tests with an UHT pilot plant showed that there was no proven formation of LAL with direct UHT-treatment at 110-130 degrees C for 10-25 min. In indirect UHT-treated milk vert small LAL amouints up to 50 ppm i.p. were detected only in those milk samples that were treated at temperatures high than 145 degrees C and holding times longer than 10 s. Autoclave sterilization in the range of 110-129 degrees C/10-25 min induced LAL amounts of 110 to 710 ppm i.p.. LAL formation in autoclave sterilized milk was almost directly dependent on heating temperature and time. Pre-treatment at temperatures below 100 degrees C induced no further LAL formation in any sterilization processes subsequent to preheating. In the pH range 6,50-6,90 LAL amounts in autoclave-sterilized milk increased directly with higher pH values at all temperatures. The varying degree of LAL formation with pH value was substantially more noticeable at higher than at lower temperatures. Increasing of lactose concentration caused only an insignificant decrease in LAL formation in autoclave-sterilized milk.
Several studies report a substantial rise in plasma catecholamines after caffeine. Epinephrine infusion induces a pressor response after nonselective beta-blockade. We studied the hemodynamic and humoral effects of drinking coffee after placebo and after both nonselective (propranolol) and beta 1-selective (metoprolol) blockade in 12 normotensive subjects. After placebo, coffee induced a rise in systolic and diastolic blood pressure and a fall in heart rate, whereas forearm blood flow did not change. Plasma catecholamines, especially epinephrine (+150%), rose and plasma renin activity, fell after drinking coffee. The effects of coffee on blood pressure, forearm blood flow, and all humoral parameters were not altered by pretreatment with propranolol or metoprolol. The fall in heart rate after coffee, however, seemed to be greater during propranolol. We conclude that the rise in plasma epinephrine after coffee was too small to reveal differences in reaction in propranolol- and metoprolol-pretreated subjects.
This paper reports on pharmacological properties of 17 alpha-cyano-methyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557), which were obtained from basic screening investigations. At high doses (100 mg/kg i.p.) STS 557 was sedatively active on the CNS, but did not show any narcotic or anticonvulsant activities. A hypothermic effect of STS 557 was found at non-sedative i.p. or oral doses in mice and rats. This was also shown for the standard levonorgestrel, doubtlessly to a lesser extent. The cardiovascular system as well as the renal excretion of urine and electrolytes were unaffected by the test compound. STS 557 was found to stimulate the spontaneous motility of the isolated rat uterus dose-dependently; an antiprogesteronic activity seems to be unlikely. STS 557 did not show any glucocorticoid or antiexudative properties. At oral dose levels of 10 and 50 mg/kg (X 4 days), STS 557 and levonorgestrel caused similar changes in the serum lipids of normolipidemic and hyperlipidemic rats. The concentration of total cholesterol was decreased, that of the FFA was increased. The triglycerides were lowered only in hyperlipidemic animals. All the pharmacological effects of STS 557 appeared at high doses, much higher than te proposed therapeutic ones.
In mice and rabbits of both sexes the acute toxicity of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) was determined after its oral or parenteral (i.p., s.c.) administration. In rabbits increasing lethality was observed following STS 557 suspended in tylose solution at the dose range of 1.0 to 3.0 g/kg p.o. or i.p. The approximate LD50-values were 1.0 to 1.5 g/kg for the i.p. route and 1.0 to 2.0 g/kg for the oral route. Levonorgestrel injected i.p. did not cause any lethality up to the dose of 3.0 g/kg. After oral or s.c. administration to mice, doses of 4.0 g/kg STS 557 were well tolerated. A dose-related toxicity occurred only after i.p. doses between 0.5 and 1.0 g/kg (STS 557), and between 2.0 and 4.0 g/kg (levonorgestrel), respectively. Using an oily vehicle for the oral route in mice, the lethal threshold dose for STS 557 was lowered to about 2.0 g/kg. In conclusion, a low oral acute toxicity was determined for STS 557 corresponding to that of other progestagens like levonorgestrel or norethisterone.
The toxicity of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557) was studied by its oral administration of 0.1, 1.0 or 10.0 mg/kg/day to Wistar rats for six months, and of 0.01, 0.1 or 1.0 mg/kg/day to beagle dogs for six months, respectively. Levonorgestrel at a dose of 1.0 mg/kg/day was used as the standard in the dog study. With respect to the progestational activity of the compound the main target organs were the hypophysis, the reproductive organs and the adrenals. Mammary hyperplasia was observed in dogs treated with STS 557 or levonorgestrel at the dose of 1.0 mg/kg/day, but in no case mammary nodules could be detected. At the dose of 1.0 mg/kg/day STS 557 and levonorgestrel were found to increase the plasma insulin response to i.v. glucose in bitches, but neither the mean blood glucose levels nor the glucose utilization were affected. Moreover, during administration of both steroids to dogs temporary changes in serum concentrations of triglycerides and total cholesterol were noted. The results obtained in rats and dogs from functional and morphological investigations did not reveal any toxic side effects of STS 557 on the liver, the kidneys, the bone marrow or on blood coagulation. The effects on the reproductive organs observed following STS 557 especially in dogs are related to both the hormonal effects of the compound and the specific response of the dog to potent progestagens.
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Analysing cardiotocographs not only fetal heart frequency and uterine contractions but also fetal movements have to be considered. Based on this knowledge 96 cardiotocographs are estimated with simultaneous observation by ultrasound. It seems to be possible to conclude from the tocograph pattern to the type of movements.
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The cardiotoxic and myelosuppressive effects of the potential antitumor antibiotics violamycin BI (VBI) and violamycin BII (VBII) were studied in rats in comparison with daunorubicin (DAU), doxorubicin (ADR) and carminomycin (CAR). Rats were intravenously given the compounds 10 times for three weeks at total doses of 0.4 to 3 times of the acute LD50. Cardiac toxicity was measured using ECG (widening of the QRS complex), and screening parameters for bone marrow suppression were white blood cell counts, hematocrit and hemoglobin values. Following the drug injections the myocardium and the bone marrow were additionally investigated by light microscopy. With the exception of ADR, all the anthracyclines tested showed a more or less strong dissociation of cardiotoxic and myelotoxic activities. VBI was found to be only toxic on the heart but not on the bone marrow, whereas DAU, VBII and CAR were predominantly toxic on the bone marrow. Only ADR showed strong cardiac toxicity as well as distinct myelosuppression. A final evaluation of VBI and VBII has to include both the antineoplastic and the toxic properties of the compounds.