Biomedical subjects
Publications and source records attributed to M Kuhn.
Moyamoya disease is a rare condition characterized by narrowing and occlusion of the internal carotid arteries. The disease usually presents as alteration of consciousness caused by intracranial hemorrhage. We describe a case of moyamoya disease presenting as seizures in a pregnant patient. The characteristic angiographic appearances and plan of management are described.
OBJECTIVES: Because pathologic mechanisms for transplant vasculopathy are still uncertain, we tested the hypothesis that endothelial function, in terms of the release of endothelium-derived relaxing factor (EDRF), is impaired in patients with evidence of angiographic transplant vasculopathy. BACKGROUND: The long-term prognosis after heart transplantation is mainly determined by the development of transplant vasculopathy. METHODS: The study included 23 patients undergoing diagnostic cardiac catheterization approximately 40 months after heart transplantation. Patients were classified into those with (n = 8) and those without (n = 15) angiographic evidence of transplant vasculopathy. Coronary flow velocity (by intravascular Doppler echocardiography) and epicardial coronary diameter (by quantitative angiography) were determined after intracoronary bolus injections (1 ml) of the endothelium-dependent dilator substance P (20 pmol) and the endothelium-independent dilators nitroglycerin (0.1 mg) and papaverine (8 mg). Substances were injected through the lumen of the Doppler catheter, which was placed into the midportion of the left anterior descending artery. RESULTS: Increases in blood flow velocity in response to substance P were significantly less in patients with than in patients without evidence of transplant vasculopathy. In addition, flow-mediated dilation of epicardial coronary arteries in response to papaverine was abolished in patients with such evidence. Vasodilation of epicardial coronary arteries in response to nitroglycerin and increases in flow velocity in response to papaverine were similar in both groups. CONCLUSIONS: These results suggest that transplant vasculopathy in heart transplant patients is associated with endothelial dysfunction (that is, impaired EDRF-mediated vasodilation). Furthermore, responsiveness of epicardial arteries to increased flow appears to be abolished in patients with evidence of transplant vasculopathy. These abnormal vascular functions may contribute to the pathogenesis of transplant vasculopathy and its vascular complications.
Virulence of Listeria monocytogenes is determined by a cluster of five genes in the order plcA, hly, mpl, actA and plcB, which are coordinately regulated by a transcriptional activator, termed PrfA. The gene for PrfA is located in front of plcA. Mutations within each of these genes reduce the virulence considerably and render the mutants unable to properly multiply and/or spread within the infected host cells. Under growth-limiting conditions PrfA-dependent proteins are preferentially synthesised. These studies indicate the existence of additional PrfA-regulated proteins in L. monocytogenes. The synthesis of catalase, superoxide dismutase, LmaA and p60 is not under the control of PrfA. These proteins seem to be also associated with virulence of L. monocytogenes. P60-related proteins are found as major extracellular proteins in all Listeria species but only p60 of L. monocytogenes is able to restore the failure of R-mutants (exhibiting a drastically reduced synthesis of p60) to adhere to 3T6 mouse fibroblasts. Adherence of L. monocytogenes to the epithelial Caco-2 cells seem to be independent of p60. The p60 protein of L. monocytogenes differs characteristically from the p60-related proteins of the nonvirulent Listeria species.
OBJECTIVE: There is accumulating evidence that oestrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The aim of this study was to measure the effects of 17 beta-oestradiol on human epicardial coronary artery tone. METHODS: Coronary artery rings were obtained from explanted hearts during cardiac transplantation. The rings were suspended in organ baths for isometric tension measurements. The rings were precontracted with prostaglandin F2 alpha, and were then exposed to either 17 beta-oestradiol (0.3 nM-3 microM) or solvent control (0.2% ethanol v/v). In some rings, cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate content were measured by radioimmunoassay. RESULTS: 17 beta-Oestradiol induced a significant relaxation [maximum effect: 84(SD 18)%]. The onset of the relaxant effect occurred within 5 min, and was maximal within 40 min. The relaxation in response to 3 microM 17 beta-oestradiol was of similar magnitude in rings with and without intact endothelium. The maximum relaxation induced by 3 microM 17 beta-oestradiol was greater in arteries from hearts obtained from women than in those obtained from men [-100.0(3.0)% v -77.5(17.6)%, respectively]. The exposure of rings to 3 microM 17 beta-oestradiol for 30 min resulted in a significant increase in both cyclic AMP and cyclic GMP content, by 88% and 182%, respectively. CONCLUSIONS: 17 beta-Oestradiol produced an endothelium independent relaxation of precontracted human coronary arteries in vitro, and this effect was associated with an increase in both cyclic AMP and the cyclic GMP content. This direct relaxant effect of oestrogens on coronary arteries may contribute to the beneficial effects of oestrogen replacement therapy in postmenopausal women.
BACKGROUND: The traditional central European approach to cardiac rehabilitation involves sending patients to an idyllic setting, where they reside for a specified period following a cardiac event. Favorable results have been demonstrated using this approach in Germany, but to our knowledge no data have been reported from Switzerland, where these programs tend to be short (4 weeks) and exercise training is concentrated (2 h daily, 6 days per week). METHODS AND RESULTS: Seventeen patients (aged 58 +/- 6 years) who resided in a rehabilitation center for 4 weeks were compared with 11 patients (aged 54 +/- 7 years) given usual community care beginning approximately 6 weeks after coronary artery bypass surgery (CABS). Exercise training consisted of 1 h of group walking twice daily, with the intensity stratified into 4 levels based on clinical status and initial exercise capacity. All patients underwent pulmonary function testing and maximal ramp exercise testing on a cycle ergometer with continuous ventilatory gas exchange and lactate analysis before and after the study period. Patients receiving beta-blockers and those with cardiomyopathy or valvular heart disease were excluded. Medication status was not changed during the study period. Although maximal oxygen uptake increased by approximately 12 percent within both groups, the change was not significant between groups. Analysis of variance demonstrated that mean lactate levels were reduced throughout exercise within both groups (p < 0.001); however, there were no differences between groups. Oxygen uptake at the lactate threshold was not different in either group after the study period. CONCLUSIONS: Similar changes occur in the functional status of post-CABS patients regardless of their participation in the short but concentrated rehabilitation programs common in Switzerland, suggesting that these programs either begin too soon after CABS or are too short to achieve training benefits.
Drug interactions occur whenever the diagnostic, preventive, therapeutic, or toxic action of a drug is modified by another substance (food or drug). Drug interactions can be harmful or beneficial. As more drugs are released, the possibility of drug interaction increases daily. Nurses need to be aware of the mechanisms for drug interactions in order to assist with prevention. The general concepts of drug interactions are presented as to the categories of occurrence: pharmacokinetic, pharmacodynamic, combined toxicities; drug-food interactions, and incompatibilities.
From 1974 to 1989, 37,392 patients were admitted to the divisions of general internal medicine of the CHDM hospitals. 19,082 of them were treated with a minor analgesic or an NSAID. In 95 of the exposed patients, an allergic or a pseudoallergic reaction to one or two of these drugs was observed. From 1981 to 1990, general practitioners, hospitals and the pharmaceutical industry reported to SANZ 158 individual cases with comparable reactions to 175 exposures of the same kind. Of the 15 different syndromes and symptoms registered in both institutions, most were reactions of the skin, mainly the usual maculopapular exanthemas (rash), urticaria and angioedema. In the CHDM, allergic or pseudoallergic reactions were observed in 0.23% of patients exposed to minor analgesics (including ASA preparations on a daily dose up to 1.0 g and pyrazolones, mainly metamizole, propyphenazone) and in 0.81% of patients exposed to NSAIDs (including the pyrazolone oxyphenbutazone). In the experience of the Comprehensive Hospital Drug Monitoring in Berne and St. Gallen (CHDM) and the Spontaneous Adverse Drug Reactions Center of Switzerland (SANZ).
Diseases of the respiratory organs comprise almost 4% of the adverse drug reactions reported to the Spontaneous Adverse Drug Reactions Center, SANZ (169 of the 4415 reports collected between 1981 and 1990). The most frequent reports were coughing caused by ACE inhibitors, attack of bronchial asthma induced by nonsteroidal anti-inflammatory drugs and beta-blocking agents, interstitial pneumopathy caused by amiodarone and sulfonamides, and respiratory depression due to benzodiazepines. The spontaneous reporting system does not allow one to determine the incidence, the reports are only of a signal-generating function. Classical semiology and special diagnostic techniques in assessing adverse drug reactions are discussed. A precise analysis of the case, temporal correlation with reaction and exposure time as well as comparisons with similar cases, together with a critical study of the literature on adverse drug reactions, remain the most important diagnostic procedures.
The reporting system of the Spontaneous Adverse Drug Reactions Center (SANZ) and the Comprehensive Hospital Drug Monitoring (CHDM) in Berne and St. Gallen are complementary ADR reporting institutions. The first collects data from the whole patient population as well as all drugs prescribed in Switzerland. The adverse drug reactions reported most frequently are easily detectable skin reactions, psychic disorders and reactions concerning the body as whole. From these reports signals can be generated, contributing to enhanced drug safety. The CHDM provides detailed information on all adverse drug reactions in a selected patient population. Because the number of patients exposed to a drug is known, a quantitative risk assessment can be calculated. The system contributes also to the detection of new ADRs. This relies partly on statistical analysis, partly on thorough clinical observations, but mostly on the combination of both. Allergic and pseudoallergic reactions were studied with some priority.
The Swiss Drug Monitoring Center SANZ operates the spontaneous reporting system in Switzerland. Spontaneous reporting schemes represent the systematic approach to the collection of individual case reports on suspected adverse drug reactions (ADR). ADR spontaneous reporting systems are an important component of the postmarketing surveillance of drugs. Spontaneous reporting systems are primarily designed to detect new and unexpected ADR; they generate signals about possible ADR and create hypotheses to be tested in pharmaco-epidemiological studies. Besides collecting, analyzing and evaluating single case reports it is important to extract those cases from the data pool which can be used to produce signals. A computer-assisted early warning system enables SANZ to detect cases with signal function and thus to track down new, rare and unexpected ADR. Carefully selected parameters can help to identify important new hazards. However, the detection of new and unexpected ADR depends to a large extent on the minds of alert physicians and the practicing clinician's awareness of and cooperation with ADR reporting.
A 66-year-old male developed lymphocytic alveolitis with bronchiolitis after 3 month's treatment with mesalazin for ulcerative colitis. The patient's symptoms disappeared after halting mesalazin and increasing the steroid dose, the reduced diffusing capacity ameliorated and the thoracic X-ray normalized. The question whether this was a case of pulmonary involvement in inflammatory bowel disease or a drug side effect.
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Alterations of pulmonary parenchyma are complications of ankylosing spondylitis. A 60-year-old man presented with extended fibrocystic changes in the right upper pulmonary lobe in the course of ankylosing spondylitis of many years duration. Pneumonia refractory to treatment and hemoptysis developed as complications necessitating pneumonectomy.
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Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 6-20 ng/kg bw.min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4: 1.5 +/- 0.11 vs. 2.19 +/- 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4: 109 +/- 8 vs. 154.7 +/- 8.94 mg/dl; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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