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Biomedical subjects

A Varga

Publications and source records attributed to A Varga.

At least 37 records · Page 2Linked to original sources
PubMed2000

Chloride channel activity of ClC-2 is modified by the actin cytoskeleton.

The chloride channel ClC-2 has been implicated in essential physiological functions, including cell-volume regulation and fluid secretion by specific epithelial tissues. Although ClC-2 is known to be activated by hyperpolarization and hypo-osmotic shock, the molecular basis for the regulation of this channel remains unclear. Here we show in the Xenopus oocyte expression system that the chloride-channel activity of ClC-2 is enhanced after treatment with the actin-disrupting agents cytochalasin and latrunkulin. These findings suggest that the actin cytoskeleton normally exerts an inhibitory effect on ClC-2 activity. An inhibitory domain was previously defined in the N-terminus of ClC-2, so we sought to determine whether this domain might interact directly with actin in binding assays in vitro. We found that a glutathione S-transferase fusion protein containing the inhibitory domain was capable of binding actin in overlay and co-sedimentation assays. Further, the binding of actin to this relatively basic peptide (pI 8.4) might be mediated through electrostatic interactions because binding was inhibited at high concentrations of NaCl with a half-maximal decrease in signal at 180 mM NaCl. This work suggests that electrostatic interactions between the N-terminus of ClC-2 and the actin cytoskeleton might have a role in the regulation of this channel.

Actins↗
PubMed2000

[Impending paradoxical embolism].

The case history of a 49-year-old female patient is reported, who was operated on because of varicose vein in the left lower extremity. A few days after the operation serious signs of cerebrovascular insult appeared. The clinical picture and the result of an urgent transoesophageal echocardiography are described; a serpentine thrombus was found to be trapped in the patent foramen ovale. During continuous intravenous heparin treatment, the patient gradually recovered, but a residual neurological deficit could be detected on discharge from the hospital. Six days after the admission, repeated transoesophageal echocardiographic examination showed no signs of intracardiac thrombus. The clinical feature of the illness, the predisposing factors, the diagnostic and therapeutic possibilities are discussed.

Diagnosis, Differential↗
PubMed2000

Increase in plasma adenosine during brain ischemia in man: a study during transient ischemic attacks, and stroke.

Adenosine is a "retaliatory metabolite" which accumulates during experimental brain ischemia and has vasodilatory and putative neuroprotective effects. The aim of this study was to assess whether human cerebral ischemia and necrosis-evaluated in the clinical models of transient ischemic attack (TIA) and stroke, respectively-acutely raise plasma adenosine levels. We studied 20 patients: 10 with TIA and 10 with stroke. In all, blood was serially sampled for assessment of plasma adenosine by an high-performance liquid chromatography method. Sampling occurred on peripheral blood during TIA and stroke upon admission, and serially thereafter every day up to 7 days and every other day up to 20 days. We found that in TIA and stroke patients, peripheral adenosine levels were increased to a similar extent upon admission (TIA = 264 +/- 53 vs. stroke = 257 +/- 60 nM, p = ns), peaked on the day 2 for TIA (300 +/- 60) and on day 3 for stroke (289 +/- 43) patients, and steadily decreased towards the normal range, reached by all TIA patients by day 5 and by stroke patients by day 15. Stroke and TIA are associated with a rapid increase in circulating plasma adenosine concentration in man, detectable in peripheral vein. The adenosine surge likely mirrors an increased production from the ischemic brain, and it lasts days (for TIA) and weeks (for stroke) after the acute event.

Adenosine↗
PubMed2000

[Significance of nuchal edema in fetuses of pregnant women under 35 years of age].

The aim of this study was to survey the connection between the fetal nuchal oedema and the increased risk of the aneuploidies. According to the prenatal care the thickness of the nuchal fold was measured on the 11-12th gestational week by 6.5 MHz transvaginal transducer (ATL-HDI and Hitachi EUB-450). Cases were underlined where the presence of nuchal oedema (> or = 3 mm) made the indication for chromosomal analysis among the 280 single pregnancies and fetal karyotyping was carried out. Nuchal oedema was observed in 72/280 cases of pregnant women under 35 years old and in 20/280 cases of that above 35 years old, the nuchal oedema was another indication beside the age. Abnormal karyotype was observed in 9/72 (12.5%) cases among the pregnant women under 35 years old and in 10/92 (10.87%) cases among the pregnancies with fetal nuchal oedema. It was also observed abnormal karyotype in 6/188 (3.19%) cases of pregnancies without nuchal oedema and in 16/280 (5.71%) cases of chromosomal analyses with or without nuchal oedema. This can be an effective method for screening the fetal aneuploidies and other fetal anomalies, both in the high risk and the normal pregnant population, especially in cases of pregnant women under 35 years old belonging to the normal genetical risk population.

Adolescent↗
PubMed2000

Normalization rate and cellular localization of phosphatidylethanol in whole blood from chronic alcoholics.

Phosphatidylethanol (PEth) is an abnormal phospholipid which is formed in the presence of ethanol, via the action of phospholipase D (PLD). PEth in blood is a potential marker of alcohol abuse. The present study was made to determine the compartmentalization and the elimination rate of PEth in human whole blood. PEth was assayed by an improved HPLC technique, with evaporative light-scattering detection. Blood from six alcoholic males was separated into different blood cell fractions. The PEth concentration in whole blood was 2.5+/-0.9 and 1.9+/-1.1 micromol/l in erythrocytes. Only one subject had detectable PEth in the mononuclear cells. Fifteen patients (13 men, two women) with chronic alcoholism, were followed as inpatients, after admission to an alcohol detoxification clinic. PEth, carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) were measured on days 1, 3, 5 and 7 after admission. Linear regression analysis of logarithmic PEth values in individuals, with measurable PEth at day 1, gave a good fit (P<0.001) with the one-compartment elimination model. The half-life was calculated as 4.0+/-0.7 days. A weak significance (P<0.05) was observed in the correlation of PEth at day 1 and half-life values of the same subjects.

Alcoholism↗
PubMed2000

The comparable diagnostic accuracies of dobutamine-stress and dipyridamole-stress echocardiographies: a meta-analysis.

BACKGROUND: Dobutamine-stress and dipyridamole-stress echocardiographies are widely used for pharmacological stress echocardiography, with wide geographical variations. OBJECTIVE: To assess whether evidence derived from the literature indicates or disapproves that either stress modality confers diagnostic superiority. METHODS: We performed a meta-analysis of peer-reviewed literature of published trials with head-to-head comparison, on the same population, of high-dose (0.84 mg/kg) dipyridamole-stress versus high-dose (up to 40 micrograms/kg per min) dobutamine-stress echocardiography. Data from 12 studies performed in 12 institutions in seven countries were analysed. Angiographic information about 818 patients was considered. RESULTS: The diagnostic accuracies of the two tests were similar (631 of 818, 77%, for dipyridamole versus 654 of 818, 80%, for dobutamine, NS). Overall sensitivities were 403 of 568 (71%) for dipyridamole and 437 of 568 (77%) for dobutamine (P < 0.05). Sensitivities for patients with single-vessel disease were 177 of 275 (64%) for dipyridamole and 203 of 275 (74%) for dobutamine (P < 0.05). Sensitivities for patients with multivessel disease were 162 of 203 (80%) for dipyridamole and 163 of 203 (80%) for dobutamine (NS). Specificities were 232 of 250 (93%) for dipyridamole and 217 of 250 (87%) for dobutamine (P < 0.05). Data from an additional 26 studies with dipyridamole alone and 47 studies with dobutamine alone were analysed. The diagnostic accuracies were 80% for dipyridamole (n = 2038 patients; 95% confidence interval 75-82%) and 82% for dobutamine (n = 4264 patients; 95% confidence interval 79-84%). CONCLUSION: High-dose dobutamine-stress and high-dose dipyridamole-stress echocardiographies have comparable diagnostic accuracies, with a slightly higher sensitivity with dobutamine and a slightly higher specificity with dipyridamole.

Cardiotonic Agents↗
PubMed2000

Cellulase production of Trichoderma reesei Rut C 30 using steam-pretreated spruce. Hydrolytic potential of cellulases on different substrates.

Various techniques are available for the conversion of lignocellulosics to fuel ethanol. During the last decade processes based on enzymatic hydrolysis of cellulose have been investigated more extensively, showing good yield on both hardwood and softwood. The cellulase production of a filamentous fungi, Trichoderma reesei Rut C 30, was examined on carbon sources obtained after steam pretreatment of spruce. These materials were washed fibrous steam-pretreated spruce (SPS), and hemicellulose hydrolysate. The hemicellulose hydrolysate contained, besides water-soluble carbohydrates, lignin and sugar degradation products, which were formed during the pretreatment and proved to be inhibitory to microorganisms. Experiments were performed in a 4-L laboratory fermentor. The hydrolytic capacity of the produced enzyme solutions was compared with two commercially available enzyme preparations, Celluclast and Iogen Cellulase, on SPS, washed SPS, and Solka Floc cellulose powder. There was no significant difference among the different enzymes produced by T. reesei Rut C 30. However, the conversion of cellulose using these enzymes was higher than that obtained with Iogen or Celluclast cellulases using steam-pretreated spruce as substrate.

Cellobiose↗
PubMed2000

Dobutamine stress echocardiography: safety in diagnosing coronary artery disease.

Dobutamine stress echocardiography is considered a relatively well-tolerated diagnostic modality, effective in the management of patients with known or suspected coronary artery disease. Adverse effects during testing are relatively frequent, precluding the achievement of a diagnostic end-point in about 5 to 10% of tests. These adverse effects, mostly tachyarrhythmias and arterial hypotension, are usually minor and self limiting. However, severe life-threatening complications, as well as death, also occur. By analysing Medline-quoted literature up to March 1999, we found 35 original studies from a single institution with more than 100 patients, as well as 2 multicentre studies, concerning the feasibility and safety of dobutamine stress echocardiography. In a cumulative total of 26438 tests performed, 79 life-threatening complications (such as acute myocardial infarction, asystole, ventricular fibrillation, sustained ventricular tachycardia or severe symptomatic hypotension) have been reported, giving an incidence of 1 severe adverse reaction per every 335 examinations. In addition, 29 isolated case reports have been published describing life-threatening complications during dobutamine echocardiography. In case reports, 2 deaths have been described, both due to acute cardiac rupture in patients with recent inferior myocardial infarction. Severe adverse reactions during dobutamine echocardiography can be ischaemia independent, and are independent of operator experience and are unpredictable; some complications can be late occurring and long lasting. As a consequence, the procedure must be clearly indicated, written informed consent has to be obtained from the patient, an attending physician must be present during testing, and long term observation of outpatients is useful in order to manage late complications. In conclusion, while the safety of dobutamine stress echocardiography was reported to be outstanding in early reports, further experience presents a substantially more worrying picture. This must be taken into account by both physicians and patients when assessing the risk-benefit profile of the procedure.

Arrhythmias, Cardiac↗
PubMed2000

Studies on the toxic interaction between monensin and tiamulin in rats: toxicity and pathology.

The characteristics of the toxic interaction between monensin and tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 and 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect and vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium and vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.

Administration, Oral↗
PubMed1999

Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. Echo-Persantine International Cooperative (EPIC) and Echo-Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: The study compared the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease. BACKGROUND: Extensive information is available on the relative diagnostic accuracy of the two tests assessed in a head-to-head fashion, whereas comparative data on their prognostic yield are largely preliminary to date. METHODS: Dipyridamole (up to 0.84 mg/kg over 10 min) atropine (up to 1 mg over 4 min) (DIP) and dobutamine (up to 40 microg/kg/min)-atropine (1 mg over 4 min) (DOB) stress tests were performed in 460 patients with known or suspected coronary artery disease. Patients were followed up for 38+/-21 months. RESULTS: The DIP was negative in 253 and positive in 207 patients. The DOB was negative in 242 and positive in 218 patients. During the follow-up, there were 80 cardiac events. For all cardiac events, the negative and positive predictive value were 83% and 17% for DOB, 84% and 19% for DIP, respectively (p = NS). Considering only cardiac death, by univariate analysis Wall-Motion Score Index (WMSI) at DIP peak dose (chi-square 13.80, p<0.0002) was the strongest predictor, followed by WMSI DOB (chi2 = 8.02, p<0.004) and WMSI at rest (chi2 = 6.85, p<0.008). By stepwise analysis, WMSI at DIP peak dose was the most important predictor (RR [relative risk] 7.4, p<0.0001). CONCLUSIONS: In patients at low-to-moderate risk of cardiac events, pharmacological stress echocardiography with either dobutamine or dipyridamole allows effective and grossly comparable, risk stratification on the basis of the presence, severity and extension of the induced ischemia.

Aged↗
PubMed1999

Comparison of combination of dipyridamole and dobutamine during echocardiography with thallium scintigraphy with thallium scintigraphy to improve viability detection.

The aim of this study was to investigate the relation between radioisotopic and echocardiographic markers of myocardial viability and their correlation with functional recovery after coronary revascularization. Myocardial viability can be detected by techniques exploring various aspects of cell physiology: thallium-201 scintigraphy and dobutamine and dipyridamole echocardiography focus on cell membrane integrity, beta-1 and adrenoceptor, and A2-adenosine receptor-mediated inotropic response, respectively. Fifty-seven patients (mean age 60+/-8 years) with previous myocardial infarction (>3 months), angiographically assessed coronary artery disease, and resting regional dysfunction underwent rest-redistribution 201-thallium scintigraphy and low-dose pharmacologic stress echo with dobutamine (up to 10 microg/kg/min), very low dose regimen of dipyridamole (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine. Criteria for viability in a 13-segment model for both techniques were percent peak activity in redistribution images >55% for thallium-201 and a decrease in wall motion score >1 grade (1 [normal] to 4 [dyskinetic]) for stress echo. Thirty patients underwent coronary revascularization (bypass surgery in 8, angioplasty in 22) and were followed up at 4 weeks from intervention with a resting echocardiogram. The rate of agreement between thallium-201 and stress echo was 63% for dipyridamole, 66% for dobutamine, and 74% for combined dipyridamole-dobutamine (p <0.05 vs dipyridamole and dobutamine). In the 30 patients who underwent revascularization, a regional resting dyssynergy was observed in 225 segments, assuming that postrevascularization functional recovery (which occurred in 126 segments) was the gold standard; combined dipyridamole-dobutamine showed a higher sensitivity (90% confidence interval [CI] 85% to 95%) than thallium-201, dobutamine, or dipyridamole (87%, CI 81% to 92%; 82%, CI 76% to 89%; and 82%, CI 76% to 89%, respectively). Specificity was lower for viability recognition with thallium-201 (61%, CI 51% to 71%) than with dobutamine (93%, CI 88% to 98%), dipyridamole (95%, CI 91% to 99%), and combined dipyridamole-dobutamine (92%; CI 87% to 97%). Combined adrenergic and adenosinergic stimulation recruits an inotropic reserve in a significant proportion of segments with preserved thallium uptake that were nonresponders after either dipyridamole or dobutamine. When functional recovery after successful revascularization is considered as the postoperative gold standard, thallium has a higher sensitivity than dipyridamole or dobutamine; this sensitivity gap is filled with combined dipyridamole-dobutamine. The specificity of all forms of pharmacologic stress echo is better than thallium-201.

Cardiotonic Agents↗
PubMed1999

Dipyridamole stress echocardiography.

Dipyridamole stress is the forerunner and prototype of pharmacological stress echo tests in the diagnosis of coronary artery disease. The safety of this test has been conclusively demonstrated as a result of extensive experience in large-scale multicenter projects. The diagnostic accuracy of dipyridamole stress echo is comparable to dobutamine and largely a function of the employed dose. Higher dosages (up to 0.84 mg/kg) are being required to achieve good sensitivity. The prognostic value has been shown to be independent and additive to clinical, exercise echocardiogram, and angiographic data. The test positive response should be titrated on the basis of severity, extent, and timing of induced dyssynergy with low positivity being associated to more anatomically and functionally severe forms of disease. Multicenter, randomized, prospective, international studies on cost-effectiveness directly comparing a noninvasive strategy centered on stress echo versus an invasive strategy centered on coronary angiography are currently ongoing.

Adrenergic beta-Agonists↗
PubMed1999

The flow-function relationship in patients with chronic coronary artery disease and reduced regional function: a Doppler transesophageal and bidimensional transthoracic echocardiography study.

BACKGROUND: Infra-low dose dipyridamole allows one to selectively explore myocardial viability. Transesophageal echocardiography Doppler measurement of left anterior descending coronary artery flow at baseline and following dipyridamole is an efficient tool to assess coronary flow response. Aim of this study was to determine the flow-function relationship during coronary vasodilatory stress in patients with coronary artery disease and baseline dysfunction. METHODS AND RESULTS: Twelve patients with resting dyssynergies and 6 controls underwent assessment of regional function and of left anterior descending blood flow velocity. Flow and function were evaluated at rest and following infra-low dose dipyridamole (0.28 mg/Kg over 4 min). Controls showed a normal function at rest and after dipyridamole. Six patients ('Responders') with resting dyssynergies showed an improvement in segments of left anterior descending artery territory, whereas the other six ones ('Non-responders') showed no functional change. Controls and 'Responders' had similar values of resting peak diastolic left anterior descending artery flow velocity both at rest and after dipyridamole, whereas 'Non-responders' showed a blunted flow response to dipyridamole. CONCLUSION: Myocardial segments with a resting dysfunction and a contractile reserve more often exhibit a residual flow response, whereas segments with fixed pattern show a flat flow response during coronary vasodilator stress.

Blood Flow Velocity↗
PubMed1999

Diagnostic and prognostic value of vasodilator stress echocardiography in asymptomatic Type 2 diabetic patients with positive exercise thallium scintigraphy: a pilot study.

AIM: To assess the diagnostic and prognostic value of vasodilator stress echocardiography in Type 2 diabetic patients with positive exercise perfusion scintigraphy. METHODS: Of an initial cohort of 50 asymptomatic Type 2 diabetic patients undergoing exercise single photon emission computed tomography (SPECT) thallium scintigraphy, 24 had a positive thallium scan, with a reversible perfusion defect. All these 24 underwent high dose (up to 0.84 mg/kg in 10 min) dipyridamole echocardiography and coronary angiography independently of stress echocardiography results. All patients were then followed for 61+/-22 months. RESULTS: Coronary angiography showed normal coronary arteries in 11 patients and significant (> 50% visually assessed diameter reduction in a major vessel) coronary artery disease in 13. Stress echocardiography showed 92% sensitivity and 100% specificity for non-invasive detection of coronary artery disease. During follow-up, five patients experienced cardiac events: heart failure in one, angina with subsequent revascularization in two, and myocardial infarction in two. Event-free survival was 100% in the 12 patients with negative and 58% in the 12 patients with positive stress echocardiography (P = 0.08 by Mantel-Cox test). CONCLUSIONS: In asymptomatic Type 2 diabetic patients with stress-induced perfusion defects, vasodilator stress echocardiography is an excellent diagnostic and prognostic tool proven with long-term follow-up.

Coronary Angiography↗
PubMed1999

Madness and method in stress echo reading.

AIM: To assess whether 'eye education' through short-term, high-intensity joint reading sessions may improve diagnostic accuracy and inter-observer agreement among beginners. METHODS AND RESULTS: Seventeen cardiologists with absent to minimal (<100 studies performed) previous stress echo experience independently and blindly read 18 stress echo studies, nine at the beginning ('pre-training' set) and nine at the end ('post-training' set) of a 2 day stress echo school which included a joint reading session of 50 tapes. The two sets were balanced as far as type of stress and image quality. The 17 observers had an average accuracy score of 51+/-16.4 before and 64.3+/-8.7% after the training (P<0.005). Concordant (i.e. >14 readers giving the same response) interpretation occurred in three out of nine studies before and in eight out of nine studies after the training (33% vs 88%, P<0.01). Kappa values went from 0.14 (poor) before to 0.39 (fair, close to moderate) after the training. CONCLUSION: Short-term, high-intensity dedicated training in stress echo, with joint reading sessions and consensus development of reading criteria significantly increased accuracy and markedly reduced the inter-observer variability in the reading of stress echoes by beginners. If there is a Shakespearean madness in stress echo reading, 'yet there is a method in't' (Hamlet, II, II, 205-206).

Clinical Competence↗