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Biomedical subjects

A Roth

Publications and source records attributed to A Roth.

At least 235 records · Page 13Linked to original sources

Evidence for an enterohepatic circulation of ochratoxin A in mice.

The distribution and elimination of [3H]ochratoxin A (OTA) from stomach content and tissue, intestine content and tissue, liver, bile, serum and urine of Swiss male mice which had received a single low dose of OTA by intubation was followed as a function of time. The profiles of radioactivity do not show a smooth decline after the absorption period, but an oscillating pattern with rapid declines followed by increases which favour the assumption of an enterohepatic circulation. Between 28% and 68% of conjugated OTA together with OTA cleavage products were found in bile giving evidence for biliary excretion of OTA and its metabolites in mice. When given i.m. to mice [3H]OTA is already found after 30 min in bile and intestine contents and its elimination patterns show several peaks confirming the biliary excretion and the enterohepatic circulation. Cholestyramine, which is known to prevent the enterohepatic circulation of drugs and toxins, changes the profile of elimination of OTA which no longer presents the cyclic pattern. This result is also in favour of an enterohepatic circulation of OTA. When phenylalanine is given together with OTA by oral gavage the toxicokinetics of the mycotoxin change completely in the different body fluids, in stomach and intestine content and tissues. Phenylalanine seems to facilitate the gastric absorption of OTA and the gastro-intestinal transit. It increases also its early excretion into urine and bile. However, its elimination pattern no longer shows the oscillating pattern. Thus phenylalanine seems to inhibit the intestinal reabsorption of OTA conjugates.

Animals↗

Resistance to isosorbide dinitrate in patients with severe chronic heart failure: incidence and attempt at hemodynamic prediction.

Oral isosorbide dinitrate has been widely used to lower elevated left ventricular filling pressure in patients with chronic heart failure. Although the recommended dose of this drug is 40 mg every 6 h, failure to respond to this dose has been observed in many patients with heart failure. In the present study the incidence of resistance to isosorbide dinitrate was evaluated and an attempt was made to identify baseline hemodynamic predictors for this phenomenon in 50 patients with severe chronic heart failure due to left ventricular systolic dysfunction (mean left ventricular ejection fraction 0.23 +/- 0.08). Twenty-seven (54%) of the 50 patients responded to 40 mg of isosorbide dinitrate (greater than 20% decrease in mean pulmonary artery wedge pressure sustained greater than or equal to 1 h) and 23 patients (46%) failed to respond. Nonresponders to 40 mg of isosorbide dinitrate had a significantly higher baseline right atrial pressure than did responders (14 +/- 5 versus 10 +/- 6 mm Hg, p less than 0.02). In addition, all 7 patients with a baseline right atrial pressure of less than 7 mm Hg and 12 of 14 patients with a baseline right atrial pressure less than 10 mm Hg responded to 40 mg. No significant differences were noted between responders and nonresponders in any other baseline hemodynamic or clinical variables, or in peak isosorbide dinitrate serum levels (32 +/- 19 ng/ml in nonresponders versus 44 +/- 36 ng/ml in responders). Of the 23 nonresponders to 40 mg, 22 received a higher dose (80 to 120 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sudden cardiac arrest in Israel: factors associated with successful resuscitation.

Out-of-hospital cardiac arrests were studied in Israel from 1984 to 1985. More than 3,500 patients in cardiac arrest received paramedic care. Eighty-three percent of cases were caused by underlying heart disease. Overall, 17% of patients with arrest caused by heart disease were admitted and 7% were discharged from the hospital. There was a wide variation in the percent discharged among the 15 paramedic service areas, ranging from 0% to 13%. Factors associated with successful resuscitation included witnessed collapse, rhythm of ventricular fibrillation, short interval from collapse to cardiopulmonary resuscitation (CPR) and delivery of advanced cardiac life support, collapse at public location, and bystander initiation of CPR. Improvements in survival are likely to result if CPR is more frequently and promptly initiated and the time to arrival of definitive paramedic care can be improved.

Aged↗

Diagnostic value of liver biopsy in alcoholic liver disease.

Because it remains debatable whether all patients with a clinical diagnosis of alcoholic liver disease should have a liver biopsy to help confirm the diagnosis, we evaluated the diagnostic value of liver biopsy in alcoholic liver disease. Studied were 108 consecutive patients who had a percutaneous liver biopsy for the first time. In all cases the patient's clinical diagnosis recorded before biopsy was compared with the histological diagnosis of an experienced histopathologist. Prebiopsy clinical data (reported alcohol intake, signs of chronic liver disease) and laboratory data (liver function tests, mean corpuscular volume, ferritin, hepatitis B serology) were reviewed. We found that a prebiopsy clinical diagnosis of alcoholic liver disease (n = 35) was confirmed by biopsy in all but one case. The prebiopsy diagnosis of alcoholic liver disease was significantly associated with a histological diagnosis of alcoholic liver disease (specificity 98%, sensitivity 79%). Individually, alcohol intake, signs of chronic liver disease, the alanine aminotransferase (ALT), the aspartate aminotransferase to ALT ratio, and the mean corpuscular volume were significantly associated with a histological diagnosis of alcoholic liver disease. When clinical and laboratory parameters were considered jointly using stepwise logistic regression, only reported alcohol intake and mean corpuscular volume were significant. Liver biopsy may not always be necessary for the identification of that broad group of patients with alcoholic liver disease.

Alanine Transaminase↗

Behavioral evidence and supporting electrophysiological observations for electroreception in the blind cave salamander, Proteus anguinus (Urodela).

Conditioning experiments revealed that Proteus perceives a back-and-forth moving (approximately 1 Hz) direct-current field and its polarity. Minimum behavioral thresholds occurred at a current density of 0.15 microA/cm2, corresponding to a voltage gradient of 0.5 mV/cm. Recordings from afferent nerve fibers showed that ampullary electroreceptors in Proteus respond as do other nonteleost receptors, i.e. with an increase in discharge rate to cathodal current and a decrease to anodal current (threshold: approximately 1 mV/cm).

Afferent Pathways↗

Combined cis-platinum plus radiation antitumor activity in locoregionally advanced squamous cell esophageal cancer.

The synergistic activity we have observed in vitro in V-79 hamster lung cells after treatment with cis-platinum combined with irradiation, stimulated a pilot study of 31 patients with inoperable locoregionally advanced squamous cell esophageal cancer. The 27 evaluable cases (22 men and 5 women--mean age 59 years) had undergone no prior radiation or cytostatic drug therapy. Histological evidence of the tumor (26 squamous cell, 1 adenocarcinoma) was obtained by endoscopy in all patients before treatment began. The patients were irradiated in two opposite thoracic fields with a total dosage of 3,000-4,000 cGy (200 cGy daily, 1,000 weekly) concurrently with 2 cycles of cis-platinum in the dosage of 30 mg/m2 iv. daily X 4 (120 mg/m2 per cycle). The results showed that cis-platinum combined with radiation showed an evident antitumor activity which included 4 complete clinical remissions and 11 partial remissions with a response rate of 56% (15/27). In two complete responders even a pathologic remission was evident (biopsy specimen) and they are now 16+ and 18+ months free of the disease. The median remission duration has been 8+ months (14+ months in complete responders) and the median survival period for the entire group is 10+ months (for responders 15+ months, p less than 0.05). Toxicity was moderate and reversible, and mainly accounted for radiation mucositis, retrosternal pain and vomiting. A mild bone marrow suppression was observed. In 2 cases esophagotracheal fistulae occurred. The results of this study show that the combination of cis-platinum and radiation might constitute successful palliative or neoadjuvant treatment for squamous cell esophageal cancer.

Carcinoma, Squamous Cell↗

Hemodynamic and volumetric effects of venodilation with nitroglycerin in chronic mitral regurgitation.

To evaluate the potential value of nitrate therapy in patients with chronic mitral regurgitation, the hemodynamic and angiographic effects of intravenous nitroglycerin were studied in 10 such patients. Nitroglycerin infusion, titrated to reduce mean pulmonary artery wedge pressure at least 20%, resulted in a significant reduction in mean blood pressure (from 91 +/- 12 to 77 +/- 13 mm Hg, p less than 0.0001), mean right atrial pressure (12 +/- 6 to 7 +/- 4 mm Hg, p less than 0.001), left ventricular end-diastolic pressure (22 +/- 7 to 13 +/- 5 mm Hg, p less than 0.0001) and peak V wave of indirect left atrial pressure (34 +/- 9 to 20 +/- 10 mm Hg, p less than 0.001). Changes in systemic vascular resistance (1,986 +/- 468 vs 1,582 +/- 534 dynes s cm-5) and forward stroke volume (39 +/- 14 vs 45 +/- 8 ml) were not statistically significant. Angiographic data showed a decrease in both end-diastolic and end-systolic left ventricular volumes (248 +/- 51 to 216 +/- 54 ml, p = 0.06 and 127 +/- 69 to 99 +/- 48 ml, p less than 0.05, respectively) and an improvement in ejection fraction, from 0.52 +/- 0.15 to 0.55 +/- 0.15 (p less than 0.05). There was no significant change in the group values for mitral regurgitant volume and fraction (from 85 +/- 32 to 72 +/- 32 ml and 67 +/- 10 to 64 +/- 5%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Are rotating tourniquets useful for left ventricular preload reduction in patients with acute myocardial infarction and heart failure?

We examined the hemodynamic effects of congesting cuffs (rotating tourniquets) in 12 patients with first acute myocardial infarction and new onset of congestive heart failure 24 to 48 hours after admission. Congesting cuffs were applied for two periods of 15 minutes each, 15 minutes apart, and inflated to 30 mm Hg and 60 mm Hg consecutively. No change was noticed in mean pulmonary artery wedge pressure, which was 20 +/- 3 mm Hg at the beginning of the study and 19 +/- 3 mm Hg at the completion (P greater than .05, NS), nor in other hemodynamic and blood gases parameters. Patients' clinical conditions remained unchanged. We conclude that application of congesting cuffs at pressures of 30 mm Hg and 60 mm Hg does not result in any change in clinical or hemodynamic data in patients with acute myocardial infarction and new onset of congestive heart failure.

Adult↗

Early intervention in acute myocardial infarction: significance for myocardial salvage of immediate intravenous streptokinase therapy followed by coronary angioplasty.

Sixteen patients with acute myocardial infarction underwent treatment with streptokinase up to 3 hours after the onset of chest pain. Nine patients (group I) received streptokinase within 1 hour of the onset of pain, and seven patients (group II) received it within 2 to 3 hours. All underwent multigated radionuclide ventriculography after streptokinase therapy and 1 week later. Percutaneous transluminal coronary angioplasty of the infarct artery was performed within 24 hours in all patients. An effort-limited treadmill stress test was performed before discharge. There was no mortality or serious complication. Mean peak total creatine kinase was 521 +/- 289 mU/ml in group I, and 1,614 +/- 709 mU/ml in group II (p less than 0.05). The mean initial left ventricular ejection fraction was 47 +/- 11% in group I and 37 +/- 10% in group II. After early angioplasty (within 24 hours) and at 1 week recovery, left ventricular ejection fraction increased to 53 +/- 9% in group I (p less than 0.05) and to 40 +/- 7% in group II (p = NS). Seven of the nine patients in group I had normal radionuclide ventriculograms at discharge compared with none of the seven patients in group II. Thrombolytic therapy administered less than 1 hour after the onset of symptoms of acute myocardial infarction followed by angioplasty of the infarct artery results in preservation of left ventricular function, whereas therapy given after 2 hours has only a limited effect.

Adult↗

Early tolerance to hemodynamic effects of high dose transdermal nitroglycerin in responders with severe chronic heart failure.

Transdermal systems for delivery of nitroglycerin have been shown to provide sustained blood levels of the drug for at least 24 hours. Investigations of hemodynamic effects of transdermal nitroglycerin in patients with heart failure have demonstrated a transient reduction in pressure lasting less than the expected 24 hours. These findings could be due to the development of circulatory tolerance to the vasodilatory effects of nitroglycerin or to insufficient drug dosing. In the present study, we compared the hemodynamic effects of the first and the second doses of high dose (120 mg) transdermal nitroglycerin given 24 hours apart in 11 responders (greater than or equal to 20% reduction in mean pulmonary artery wedge pressure lasting greater than or equal to 2 hours). Initiation of nitroglycerin therapy resulted in a significant reduction in mean right atrial pressure lasting for 14 hours and in a reduction in mean pulmonary artery and mean pulmonary artery wedge pressures lasting 24 hours. After administration of the second dose, mean right atrial pressure at 2 hours (9 +/- 5 versus 7 +/- 4 mm Hg), 4 hours (8 +/- 5 versus 6 +/- 4 mm Hg) and 8 hours (8 +/- 5 versus 6 +/- 3 mm Hg) was higher than after the first dose (p less than 0.05). Both mean pulmonary artery and mean pulmonary artery wedge pressures were significantly higher after the second nitroglycerin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure.

Sustained therapy with nitroglycerin (NTG) has been reported to provoke the development of early tolerance. Because continuous intravenous NTG infusion is commonly used in patients with coronary artery disease and heart failure, we evaluated the incidence of early tolerance developed within the first 24 hr of therapy in 31 responders to NTG. After documentation of response to NTG, defined as a 10 mm Hg or greater or a 30% or greater reduction in mean pulmonary arterial wedge pressure (PAWP), 16 patients were blindly, randomly assigned to receive placebo and 15 patients were continued on same-dose NTG. Both groups showed an identical fall in PAWP at peak NTG titration (11 +/- 4 mm Hg). Discontinuation of NTG in the placebo group resulted in a rapid increase in PAWP to levels not significantly different from baseline (19 +/- 5 mm Hg at 2 hr vs 23 +/- 6 mm Hg at baseline; p = NS). In the NTG group, PAWP fell from 27 +/- 9 to 14 +/- 7 mm Hg, was 16 +/- 9 mm Hg at 2 hr (p less than .05 vs baseline), and continued to be significantly lower than baseline for 8 hr; however, due to attenuation of effect, PAWP values at 12, 20, and 24 hr were not significantly different from placebo or baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Hemodynamic effects of intravenous isosorbide dinitrate and nitroglycerine in acute myocardial infarction and elevated pulmonary artery wedge pressure.

We compared in a randomized fashion the hemodynamic effects of intravenous (IV) isosorbide dinitrate (ISDN) and nitroglycerine (NTG) in 45 patients with acute myocardial infarction and elevated pulmonary artery wedge pressure (Paw). Titration of ISDN dose to lower Paw greater than or equal to 25 percent resulted in a fall of this parameter from 32 +/- 8 to 24 +/- 5 mm Hg and was associated with a fall in mean blood pressure (96 +/- 15 to 90 +/- 14 mm Hg, p less than 0.05), systemic vascular resistance (1715 +/- 572 to 1548 +/- 414 dynes X s X cm-5, (p less than 0.05), pulmonary vascular resistance (182 +/- 106 to 154 +/- 78 dynes X s X cm-5, p less than 0.05) and mean right atrial pressure (11 +/- 4 to 7 +/- 4 mm Hg, p less than 0.05). In addition, ISDN significantly (p less than 0.05) increased cardiac index from 2.37 +/- 0.54 to 2.54 +/- 0.59 L/min/m2, stroke volume index from 28 +/- 8 to 31 +/- 8 ml/m2, and stroke work index from 28 +/- 11 to 31 +/- 12 g X m/m2. The ISDN dose ranged from 50 to 533 micrograms/min (mean +/- SD 326 +/- 176 micrograms/min) and could not be predicted from baseline hemodynamic values. A comparison between the effect of ISDN and NTG in doses producing comparable reduction in Paw showed similar hemodynamic changes. It was concluded that IV ISDN in patients with elevated mean pulmonary artery wedge pressure due to acute myocardial infarction results in a decrease in right and left ventricular preload and afterload and improvement of cardiac output and cardiac work. The effective dose ranges from 50 to 533 micrograms/min and cannot be predicted from baseline hemodynamic values. In doses producing comparable reduction in Paw, ISDN and NTG had similar hemodynamic effects.

Aged↗

Pharmacokinetic and pharmacodynamic effects of the novel benzodiazepine antagonist 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one in humans.

2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (CGS 8216) is pharmacologically characterized as benzodiazepine antagonist with low inverse agonistic effects. Single oral doses up to 650 mg and subchronic doses up to 100 mg daily for seven days are well tolerated by young healthy volunteers. Plasma concentrations of CGS 8216 are variable, not dose-related and relatively low considering the doses administered. A high plasma concentration ratio of metabolite vs. parent compound (3:1) points to an extensive gastrointestinal first-pass metabolism. CGS 8216 influences the human electroencephalogram similar to anxiolytic and vigilance enhancing drugs in doses which do not change performance of psychometric tests. CGS 8216 antagonizes the diazepam-induced impairment of alertness.

Adult↗