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Biomedical subjects

W Adam

Publications and source records attributed to W Adam.

At least 19 recordsLinked to original sources

Photochemical DNA modifications induced by 1,2-dioxetanes.

1,2-Dioxetanes are efficient sources of triplet excited carbonyl compounds, into which they decompose on thermal or photochemical activation. In the presence of DNA, the decomposition of dioxetanes gives rise to DNA modifications, which have been studied by means of specific repair endonucleases. Cyclobutane pyrimidine dimers, which are generated by triplet-triplet energy transfer, were detected by a UV endonuclease; they made up between 2% and 30% of the total modifications recognized by a crude repair endonuclease preparation from Micrococcus luteus. For various 1,2-dioxetanes, the yield of pyrimidine dimers was proportional to their triplet excitation flux. DNA strand breaks, sites of base loss (AP sites; recognized by exonuclease III and endonuclease IV) and dihydropyrimidines (recognized by endonuclease III) were found to represent only a small fraction of the modifications. The majority of the modifications detected were recognized by formamidopyrimidine-DNA glycosylase (FPG protein) and represent 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) residues or other yet not defined base modifications which are recognized by this enzyme. The modifications were generated in similar relative yields by thermal and photo-induced decomposition of the 1,2-dioxetanes and therefore emanate under both conditions from the excited carbonyl compounds. The formation of the FPG protein-sensitive modifications was efficiently quenched by azide anions; the Stern-Volmer quenching of these modifications was 150-fold more effective than that of the pyrimidine dimers. The relative amounts of the two types of modifications were strongly dependent on the structure of the 1,2-dioxetanes and on the concentration of molecular oxygen. Singlet oxygen appears to be involved only to some extent in the generation of the FPG protein-sensitive base modifications as their yield was only moderately (approximately 2-fold) increased in D2O as solvent. A mechanism is suggested in which oxidized guanine is predominantly formed by a single-electron-transfer reaction of the triplet excited carbonyl product derived from the 1,2-dioxetane, followed by unknown secondary oxidations, which involve molecular oxygen and/or undecomposed 1,2-dioxetane.

DNA

Progressive soft tissue uptake of Tc-99m MDP reflecting metastatic microcalcification.

A 49-year-old woman had longstanding renal impairment. Markedly increased uptake of Tc-99m MDP in the heart, lungs, and kidneys was an incidental finding on bone scintigraphy performed to exclude metastatic bone disease. These findings persisted on repeat bone imaging 1 year later. In addition, gastric and skeletal muscle uptake was subsequently seen. Soft tissue microcalcification was confirmed by computed tomography and renal biopsy. A consideration of the differential diagnosis is presented.

Bone Neoplasms

[Experiences with 800 mg ibuprofen retard in ambulatory patients with activated osteoarthrosis and extra-articular rheumatic manifestations].

The efficacy and tolerance of ibuprofen retard at a dose of 2 x 800 mg daily was investigated in an open multicenter study over a period of 3 weeks on 7931 out-patients with activated degenerative joint disease and/or extraarticular rheumatic symptoms. The overall assessment of the treatment, made by the patients and physicians at the end of the observational study, was positive in 94.7% and 95.7% of the cases, respectively. The therapy was assessed as inadequate in only 5.2% and 4.3% of the cases, respectively. The patient's compliance was assessed by the physicians as being high at 92.6%. Adverse events during the treatment were observed in 7.8% of the patients; these concerned mainly intestinal complaints. Gastrointestinal bleeding was observed in five cases. One patient died from a heart attack during the observational study; this was not related to the drug therapy. The frequency of side effects was within the range of the findings from earlier studies with conventional drug formulations. It can be concluded from the results obtained that ibuprofen 800 retard is well-suited for and demonstrates a good tolerance in the treatment of acute, chronic-persisting, and chronic-intermittent painful conditions of degenerative joint disease and extraarticular rheumatic symptoms.

Adult

The use of carvedilol in elderly hypertensive patients.

Carvedilol, a beta-blocking drug with vasodilator activity, has been used in 4 studies in 107 elderly patients with essential hypertension and has reduced blood pressure effectively. In the first study the pharmacokinetics and clinical response were compared between 21 patients greater than 65 years of age and 8 patients aged 35-50 years). The peak blood levels, time to maximal concentration, area under the curve, half-life and trough level of the drug with chronic administration did not differ. The clinical responses to the drug were similar, with a greater fall in systolic blood pressure in the older group. However the initial systolic blood pressure in the older group was higher. Carvedilol was compared with metoprolol, pindolol and nitrendipine in elderly patients. The responses to carvedilol were at least equal to those obtained with the other drugs. Control was achieved in the three studies with once-daily therapy. There was no significant postural hypotensive effect. A feature of all studies was the large number of patients who responded to carvedilol. The side-effect profile of the drug was acceptable; headache and dizziness were more common than with placebo or the comparison drugs and were frequently associated. There were no adverse biochemical effects and the lipid profile was not altered. Carvedilol is an effective antihypertensive drug that lowers blood pressure equally well in the young and the old.

Adrenergic beta-Antagonists

Effects of testosterone undecanoate on sexual potency and the hypothalamic-pituitary-gonadal axis of impotent males.

A double-blind comparison was made of the effects of testosterone undecanoate (TU) and placebo on sexual potency of 29 impotent men ages 45--75. The main criteria for inclusion in the study were a reduced or nonexistent capacity to have an erection during intercourse and no clinical signs of endocrinological pathology. All patients received placebo for 2 weeks. Then TU was given at a daily dose of 120 mg to 13 patients selected at random while the other patients continued to receive placebo. After 8 weeks all patients received placebo again for 2 weeks. An improvement in sexual potency was reported by five patients given TU and eight patients given placebo, with no significant differences between the groups. Treatment with TU influenced neither the hypothalamic-pituitary-gonadal axis, as judged by levels of prolactin, LH, FSH, and the LHRH-induced LH/FSH response, nor depression, anxiety, and somatic scores or performance tests. The only specific effect of TU treatment was to decrease the total plasma testosterone level. The present findings show pharmacotherapy with androgens to be no more effective than placebo in restoring sexual potency to sexually impotent men without androgen deficiency. Further studies may be needed to elucidate fully the effects of androgen administration on psychological and endocrinological variables in such patients.

Aged

Treatment of mild hypertension in elderly males.

1. Males, born between 1900 and 1925, with mild hypertension have been treated for periods varying from 300 to 2000 days. 2. The life and death status of all patients (except two) was known on 1st November 1978. 3. A group of patients with mild hypertension receiving treatment based on a thiazide diuretic had a greater mortality than the other drug-treated group. 4. The increased mortality was caused by an increased number of myocardial infarcts. 5. Elderly male patients with mild hypertension probably have preexisting vascular disease and therapy should not automatically be started. If therapy is started, beta-adrenoreceptor-blocking drugs may be a preferred therapy.

Adrenergic beta-Antagonists

[Herpes virus hominis diseases (author's transl)].

In a 14-year-old girl treated with cytostatics because of leukaemia a severe and chronic atypical herpes virus hominis infection occurred. The same disease also occurred in a 30-year-old man under immunosuppression after a renal transplant. The skin reactions posed diagnostic and therapeutic problems. In both cases withdrawal of the cytostatic agent or drastic reduction of the immunosuppressive drug were successful therapeutically.

Adolescent

The effect of labetalol in the treatment of severe drug-resistant hypertension.

Twenty-two hypertensive patients from a large clinic, who were resistant to conventional therapy, were entered into this study. Most patients previously had received beta-blocking drugs, thiazide diuretics, alpha-methyl-dopa, or vasodilator drugs (hydrallazine or prazosin) which failed to control their blood pressure. The therapy with vasodilator drugs was discontinued, and the therapy with labetalol (a drug with both alpha-blocking and beta-blocking effect) was commenced. Subsequently, as the blood pressure came under control, other drugs that the patients were taking were also withdrawn. In 13 of the 22 patients, labetalol enabled the blood pressure to be controlled at acceptable levels. In six patients, the response was not considered to be sufficient to justify continuation of labetalol therapy. In three patients, the drug was withdrawn because of postural hypotension in one patient, intractable diarrhoea in another, and an allergic-type skin rash in the third. In certain patients, postural changes in blood pressure were observed, but this rarely produced symptoms. It is suggested that, if blood pressure control is not achieved with a thiazide diuretic and a beta-blocking drug, then labetalol should be introduced and the beta-blocking drug should be withdrawn.

Aged

Hypertension treated by salt restriction.

31 patients with a diastolic blood-pressure between 95 and 109 mm Hg have been treated for two years with a regimen involving a moderate restriction of salt in the diet. The results are compared with those in a control group and in a drug-treated group. Salt restriction has reduced the diastolic blood-pressure by 7.3+/-1.6 mm Hg, a result similar to that in patients treated with antihypertensive drugs. In the untreated group the diastolic blood-pressure rose by 1.8+/-1.1 mm Hg. Most patients did not achieve the desired amount of salt restriction and a stricter adherence to the diet might have caused further falls in blood-pressure. Excessive salt intake is probably a major cause of the epidemic of hypertension in "civilised" countries and a reduction in salt intake may help to control the epidemic. In persons with a diastolic blood-pressure between 90 and 105 mm Hg salt restriction should be tried before drugs.

Blood Pressure

Treatment of mild hypertension.

1. A total of 206 patients, elderly males with hypertension (diastolic blood pressure 95--110 mmHg) were followed for periods varying from 1 to 5 years, 107 patients with diastolic blood pressure less than 95 mmHg were followed over the same period, and 101 patients with diastolic blood pressure greater than or equal to 110 mmHg were also followed. 2. The mortality of each group and the effect of therapy for hypertension on mortality has been compared. 3. The incidence of myocardial infarct in the group treated with thiazide diuretics is greater than in the other groups. 4. It would appear unlikely that therapy will improve the prognosis in elderly people with mild hypertension.

Benzothiadiazines

Gas sterilization of fiber endoscopes.

Excitants of disease can be transmitted by endoscopes from one patient to another. Owing to their complicated construction and the heat-sensitive material fiber glass endoscopes are difficult to disinfect or sterilize. Of the known procedures of sterilization only gas sterilization with ethylene oxide can be used. Clinical examinations and laboratory experiments demonstrate the reliable efficacy of this procedure of sterilization of fiber glass endoscopes. On account of known risks the indications for gas sterilization are compiled.

Bacteria

New peroxides and their antimicrobial activity.

Antimicrobial activity of hydroperoxides and cyclic peroxides has been studied. 2,4-Dihydroperoxy-2,4-dimethylpentane (1) and 2,5-dihydroperoxy-2,5-dimethylhexane (2) were active against microorganism, but 1 showed a large specially against C. albicans, M. luteus and B. subtilis with a MIC value of 31.5 mcg/ml.

Bacillus subtilis