[cDNA cloning of foot-and-mouth disease virus].
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Biomedical subjects
Publications and source records attributed to S Weber.
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The effect of cimetidine on the new beta-blocker betaxolol (Kerlone) was investigated in 7 healthy volunteers. Propranolol was used as a reference beta-blocking drug. In the control study, a single oral dose of propranolol (80 mg) was given (D0) followed by 5 daily doses of cimetidine (1 g) (D1-D6) and a second oral dose of propranolol (D7). The study was repeated with 20 mg of betaxolol replacing the propranolol dose. The oral clearance of propranolol was significantly decreased (21%). No significant effect of cimetidine on the kinetics of betaxolol was observed.
The presence of ischaemic myocardial tissues in necrotic territories and the usefulness of revascularizing these territories are controversial matters. We have determined the existence of this phenomenon by the per-angioplastic intracoronary ECG method, and we have compared the sensitivities of intracoronary ECG and surface ECG. Intracoronary EVG is achieved by using the mobile teflon-coated guide wire of coronary angioplasty as a unipolar epicardial electrode. Being epicardial and localized, the electrode explores a limited area of the myocardium, distal to the artery being dilated and momentarily occluded by the balloon during inflations. The study involved 12 patients (mean age 53.7 years) who presented with the following criteria of admission: transmural myocardial infarction, presence of a Q wave on two leads, akinetic segment at ventriculography and coronary stenosis or occlusion amenable to angioplasty. Patients with collateral circulation between the larger epicardial vessels were excluded. Intracoronary ECG recordings were taken before, during and after inflations. In 9 out of 12 patients the ST segments was elevated by 1.3 mV on average between inflations (S.D. 3.14 mV) and by 4.8 mV (S.D. 3.99 mV) during inflations. These high standard deviations were due to major inter- and intra-individual variations of ST. The difference was significant (p less than 0.05) at variance analysis. No variation of ST was observed in 3 patients. Only one of the 12 patients had elevated ST on both surface ECG and intracoronary ECG tracings. Thus, intracoronary ECG is a sensitive method to evaluate myocardial ischaemia during coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)
Laser fluorimetry of reduced nicotinamide-adenine-dinucleotide (NADH) p6 a new technique used for in situ and real-time study of myocardial metabolism. We have evaluated its applicability to clinical situations in 5 patients undergoing haemodynamic exploration. An optic fibre was inserted in a catheter the end of which was positioned in the postero-diaphragmatic part of the left ventricle. The optic fibre was connected to a Cilas-Alcatel fluorimeter. Variations in fluorescence were studied during variations in left ventricular end-diastolic pressure (LVEDP) and during coronary arteriography. An increase in LVEDP resulted in a slight increase in NADH, but when the LVEDP was reduced by a nitroglycerin infusion, NADH fell significantly below baseline values in patients with coronary disease. This effect was most probably due to redistribution of the coronary blood flow from healthy territories to ischaemic territories. In patients without significant coronary stenosis, NADH was not modified by an injection of 10 ml of contrast medium into the right coronary artery. In contrast, in patients with severe stenosis NADH fluorescence significantly increased during the injection, reflecting the ischaemia or myocardial anoxia induced by the contrast medium. NADH laser fluorimetry therefore seems to be promising as a means of exploring myocardial metabolism during cardiac catheterization.
Although unstable angina is an extremely common and often initial manifestation of coronary disease, few controlled studies of its treatment have been carried out. This relative dearth of information is due to the methodological problems raised by the evaluation of unstable angina. Unlike the definition of myocardial infarction, that of unstable angina--i.e. of a population of coronary patients who from time to time are at a high risk of myocardial infarction or death--is neither unequivocal nor easy to standardize. It follows that the patient population ultimately selected for controlled trials is but a small part of all unstable angina patients. The representativeness of patients involved in therapeutic trials is probably approximate. Moreover, the current criteria for assessment of effectiveness are either the clinical signs of angina in the short term or the incidence of myocardial infarction and changes in survival curves in the mid- and long terms. A more precise definition of criteria of inclusion, leading to an homogeneous population, and the development of a simple and reliable method for detecting and quantifying myocardial ischaemia, both being used as intermediate criteria of assessment, would undoubtedly improve the quality of therapeutic trials in unstable angina and, mostly, their applicability to daily therapeutic practice.
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Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.
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Extraction of a basement-membrane-producing mouse tumor with 6 M guanidine/HCl in the presence of protease inhibitors allowed the purification of the genuine form of the matrix protein nidogen (Mr = 150,000) and, in addition, two defined fragments (Mr = 130,000 and 100,000). Smaller fragments (Mr = 80,000 and 40,000) were obtained under conditions with less stringent control of endogenous proteolysis. Intact nidogen and the larger fragments were similar in amino acid and carbohydrate (about 5%) composition, the presence of a single polypeptide chain, conformational features as revealed by CD spectroscopy and all shared major epitopes located on the Mr = 80,000 fragment. Additional epitopes were found on intact nidogen and the Mr = 130,000 fragment. Nidogen and the various fragments possess different N-terminal amino acid sequences indicating a stepwise degradation from the N-terminal end of the molecule. Electron microscopical and hydrodynamic studies of the Mr = 80,000 fragment demonstrated a structure consisting of a globular head connected to a thin tail. Intact nidogen appears to contain a somewhat larger globule but the same tail, which is terminated at its opposite end by a second, smaller globular structure. The data suggest a multidomain structure for nidogen containing sites highly susceptible to proteolytic cleavage.
We evaluated the effect of dipyridamole on thallium-201 myocardial perfusion in 23 patients with progressive systemic sclerosis (PSS) with diffuse scleroderma. Thallium-201 single photon emission computed tomography (SPECT) was performed at rest and after coronary artery vasodilatation with intravenous dipyridamole (0.14 mg/kg/min for four minutes). The left myocardium was divided into nine segments; each segment was graded as 2.0, 1.5, 1.0, 0.5, 0 (zero represents no activity). Dipyridamole significantly improved resting thallium-201 myocardial perfusion: the mean (SD) number of segments with thallium defects decreased from 6.0 (2.1) at rest to 4.1 (2.5) after dipyridamole (p less than 0.0001); the mean (SD) score in segments with resting defects increased from 0.92 (0.24) at rest to 1.13 (0.38) after dipyridamole (p less than 0.0001); the mean (SD) global score per patient increased from 10.2 (1.8) at rest to 11.4 (2.1) after dipyridamole (p less than 0.02); the global score increased by at least 2.0 in 12 patients and worsened by at least 2.0 in three patients only (p = 0.05). The results of this acute study suggest that some drugs with potent vasodilator activity on small coronary arteries may be beneficial in the treatment of PSS patients with thallium-201 myocardial perfusion abnormalities.
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Simultaneous measurements of train-of-four (TOF) responses by integrated electromyography (IEMG) and twitch force were compared for atracurium, vecuronium, and succinylcholine in 30 subjects during nitrous oxide-fentanyl anesthesia. Determinations of TOF were made during neuromuscular blockade (NMB) onset and recovery. Scattergrams and least squares regression lines were plotted, and z-tests for parallel slope and common intercept were used to compare lines. Data for atracurium and vecuronium were indistinguishable in all groups (z less than 0.05), and therefore pooled to represent nondepolarizing blockade. During onset of nondepolarizing NMB, TOF showed a linear relationship indistinguishable from the line of identity (slope 0.93, intercept -0.06, z less than 0.05). During recovery the intercept was unchanged (z greater than 0.05), but the slope was significantly changed, indicating mechanical TOF lags behind IEMG during recovery. This finding is important for interpretation of IEMG when used for clinical monitoring. Comparison of data for depolarizing NMB shows more complex relationships. Integrated electromyography is found to be convenient and reliable for monitoring nondepolarizing NMB.
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Warm-antibody autoimmune hemolytic anemia (AIHA) is a rare but typical extraintestinal complication of ulcerative colitis. Seven cases with this condition are reported here and 24 further cases from the literature are reviewed. There were no essential differences between the two groups of patients with respect to clinical and immuno-hematological findings. However, the introduction of immunosuppressive drugs has led to a change in therapy and prognosis in recent years. Our observations suggest that treatment with steroids and azathioprine is to be recommended, with accompanying therapy of the underlying disease. In patients failing to respond to this immunosuppressive regimen, splenectomy or surgical treatment of the affected intestines must be considered. For every patient with ulcerative colitis and hyperregenerative anemia the possibility of warm autoantibody formation must be ruled out by performing the direct antiglobulin test.
A 24-year-old, 4-months pregnant woman developed an acute thrombosis of a St. Jude Medical aortic valve prosthesis. Upon admission, she was in cardiogenic shock. A thrombectomy was achieved in emergency under cardiopulmonary bypass. The patient survived but not the fetus. Diagnosis, surgical procedure, anticoagulation drugs and valve prostheses in pregnant women are discussed.
The RAD6 gene of Saccharomyces cerevisiae is required for postreplication repair of UV-damaged DNA, for induced mutagenesis, and for sporulation. We have mapped the transcripts and determined the nucleotide sequence of the cloned RAD6 gene. The RAD6 gene encodes two transcripts of 0.98 and 0.86 kilobases which differ only in their 3' termini. The transcribed region contains an open reading frame of 516 nucleotides. The rad6-1 and rad6-3 mutant alleles, which we have cloned and sequenced, introduce amber and ochre nonsense mutations, respectively, into the open reading frame, proving that it encodes the RAD6 protein. The RAD6 protein predicted by the nucleotide sequence is 172 amino acids long, has a molecular weight of 19,704, and contains 23.3% acidic and 11.6% basic residues. Its most striking feature is the highly acidic carboxyl terminus: 20 of the 23 terminal amino acids are acidic, including 13 consecutive aspartates. RAD6 protein thus resembles high mobility group proteins HMG-1 and HMG-2, which each contain a carboxyl-proximal tract of acidic amino acids.