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Biomedical subjects

R B Stewart

Publications and source records attributed to R B Stewart.

At least 91 records · Page 5Linked to original sources

Serodiagnosis of ovine paratuberculosis, using lipoarabinomannan in an enzyme-linked immunosorbent assay.

The use of lipoarabinomannan (LAM; obtained from Mycobacterium paratuberculosis) in and ELISA (LAM-ELISA) to test 75 sheep sera from a paratuberculosis-infected flock resulted in an approximate threefold increase in sensitivity (from 23.5% to 70.6%), compared with the use of Annau's polysaccharide in a complement fixation test (P-CFT). Even after manipulation of the LAM-ELISA cut-off value to produce a specificity of 100% to match that of the P-CFT, the sensitivity still was approximately twofold greater than that of the P-CFT. Anti-bovine monoclonal antiglobulin-enzyme conjugates matched commercially available anti-ovine polyclonal antiglobulin-enzyme conjugates with respect to sensitivity and specificity. False-positive results were found to be less frequent after combining 2 serodiagnostic tests, LAM-ELISA and D antigenagar gel immunodiffusion, resulting in an increase in specificity from 88.1% to 95.2%. The repeatability of true seropositive and seronegative results was found to be 89.5% and 91.1%, respectively, for sera obtained less than or equal to 1 month prior to slaughter and 91.7% and 95.5%, respectively, for reanalysis of sera obtained at the time of slaughter.

Animals↗

Prospective evaluation of initially ineffective defibrillation pulses on subsequent defibrillation success during ventricular fibrillation in survivors of cardiac arrest.

The effect of initially ineffective defibrillation pulses on subsequent defibrillation success is not known. Therefore, the voltage, current and energy at the defibrillation threshold were compared with the defibrillation rescue pulse voltage, current and energy that terminated ventricular fibrillation when an ineffective pulse just below the defibrillation threshold had been used initially. This lower amplitude ineffective pulse was termed a "subdefibrillation threshold" pulse. The pulse that restored sinus rhythm after the subdefibrillation threshold pulse was delivered was termed the "subdefibrillation threshold rescue pulse." This comparison was undertaken, intraoperatively, in 14 out-of-hospital cardiac arrest survivors using a sequential-pulse catheter-patch defibrillation system. Each of the 14 patients required higher voltage, current, delivered energy and stored energy for defibrillation with the subdefibrillation threshold rescue pulse than with the defibrillation threshold pulse. The defibrillation threshold voltage was 451 +/- 127 volts compared with a subdefibrillation threshold rescue voltage of 585 +/- 147 volts (p less than 0.00002). The defibrillation threshold current was 5.5 +/- 2.4 amps compared with a subdefibrillation threshold rescue current of 7.2 +/- 2.7 amps (p less than 0.00001). Delivered and stored energies were 10.9 +/- 7.4 and 12.3 +/- 7.2J, respectively, for the defibrillation threshold pulse and were 17.6 +/- 9.4 J (p less than 0.00002) and 20.5 +/- 9.3 J (p less than 0.00005), respectively, for the subdefibrillation threshold rescue pulse. It is concluded that the risk of requiring considerably higher energies than anticipated for defibrillation must be incurred, should defibrillation fail because of an initially insufficient defibrillation pulse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Developments, complications and limitations of catheter-mediated electrical ablation of posterior accessory atrioventricular pathways.

Nineteen patients with posterior accessory pathways and disabling, refractory arrhythmias, underwent catheter ablation using standard defibrillator pulses at energy settings of 150 to 400 J. Accessory pathway ablation was successful in 13 of 19 (68%). Effective catheter ablation correlated with local ventriculoatrial (VA) intervals determined from the coronary sinus catheter at the site of earliest retrograde atrial activation during orthodromic reciprocating tachycardia. In 12 of the 13 successfully ablated patients, the local VA interval was less than 80 ms. In 4 of the 6 unsuccessfully treated patients, the local VA interval was greater than or equal to 80 ms, p less than 0.01. Transient abnormalities noted with the procedure included sinus bradycardia (3 patients), atrioventricular block (5), accelerated junctional rhythm (3), ectopic atrial tachycardia (2), myocardial depression (1), "ischemic" appearing T-wave inversions (10) and hemodynamically insignificant small pericardial effusions (5) Creatine kinase-MB increased from 3 +/- 2 U/liter to 26 +/- 18 U/liter (p less than 0.001), 4 to 8 hours after ablation. In addition, electrical shorts occurring during the ablation procedure in 2 patients were identified and corrected only with oscilloscopic monitoring of voltage and current waveforms. Significant adverse sequelae were seen in 4 patients. Three patients required sternotomy for control of cardiac tamponade secondary to a ruptured coronary sinus and 1 patient had a small posterior left ventricular infarction related to spasm of a right coronary artery extension branch. Coronary sinus rupture correlated with the ratio of catheter diameter to coronary sinus diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Angiotensin II reduces voluntary alcohol intake in the rat.

The voluntary intake of alcohol has been shown to be attenuated by a variety of manipulations which increase activity in the renin-angiotensin system. In the present study we examined the effects of peripheral injections of the peptide angiotensin II on alcohol drinking. The peptide produced a dose-dependent decrease in alcohol intake with 20 micrograms/kg having little effect, 200 micrograms/kg reducing intake by approximately 50% and 1 mg/kg virtually abolishing all alcohol drinking. This decrease was not due to a peptide induced motor deficit, or state of sickness, and could also not be accounted for by the increased water intake, or by a change in pharmacokinetics and taste function. These data provide direct evidence that angiotensin II can modulate voluntary alcohol drinking. The possibility that the level of angiotensin II serves as a satiety signal in alcohol drinking is discussed.

Alcohol Drinking↗

Attenuation of alcohol intake by a serotonin uptake inhibitor: evidence for mediation through the renin-angiotensin system.

Although the serotonin uptake inhibitors have been shown to reduce alcohol intake in both animals and man, the mechanism of this effect is unclear. It is known that enhanced serotonergic activity can stimulate activity in the renin-angiotensin system and that elevated activity in the renin-angiotensin system can reduce voluntary alcohol intake. Therefore, serotonin uptake inhibitors such as fluoxetine might exert their effect on alcohol intake, in part, through the renin-angiotensin system. The present experiment assesses this possibility by examining the effect of the angiotensin converting enzyme inhibitor, enalapril, on the fluoxetine-induced decrease in alcohol intake. Four groups of rats were offered limited access to alcohol for 1 hr each day. When intake stabilized each group was injected with 2.5, 5.0 or 10.0 mg/kg of fluoxetine or the saline vehicle 1 hr prior to the access to alcohol. Fluoxetine produced a dose-dependent decrease in alcohol intake. Following this, all groups received injections of 1 mg/kg of the angiotensin converting enzyme inhibitor, enalapril, 40 min prior to the fluoxetine. Enalapril had no effect on alcohol intake in the saline group, but reversed the suppression in alcohol intake produced by the 2.5 mg/kg and 5.0 mg/kg doses of fluoxetine and partially reversed the effect of the 10.0 mg/kg dose. These findings indicate that the fluoxetine-induced reduction in alcohol intake may, in part, be mediated through the renin-angiotensin system.

Alcohol Drinking↗

Angiotensin II-induced suppression of alcohol intake and its reversal by the angiotensin antagonist Sar-1 Thr-8 angiotensin II.

The effects of three doses of angiotensin II (AII) on alcohol consumption using the limited access procedure were studied. Fifty and 100 micrograms/kg AII administered subcutaneously (SC) did not alter alcohol intake while 200 micrograms/kg suppressed alcohol intake. These findings confirm previous work and show that AII begins to be effective in reducing alcohol intake in the range of 200 micrograms/kg. In the second part of the study, the AII antagonist Sar-1 Thr-8 AII (500 micrograms/kg SC) was given immediately prior to the administration of either saline or 200 micrograms/kg AII. In the control group treated with saline, the antagonist had no effect of its own on intake but completely blocked the suppressive effect of the 200 micrograms/kg dose AII on alcohol consumption. These findings indicate that the reduction in alcohol intake produced by AII is mediated by events occurring at the receptor level.

Alcohol Drinking↗

Cataracts in Dunedin Program participants: an evaluation of risk factors.

A geriatric health screening program in Dunedin, Florida, was used to evaluate risk factors leading to development of cataracts. A total of 2,787 participants completed the fourth yearly visit to the program. At the time of the fourth visit, 49.3% of women (mean age 75.1 years) and 38.2% of men (mean age 75.4 years) reported the presence of cataracts. Age was found to be the most significant risk factor in cataract development (P less than .0001). Both men and women with cataracts had significantly lower serum cholesterol concentrations than subjects without cataracts. After adjusting for age and sex, diazepam (P less than .03), furosemide (P less than .04), isosorbide (P less than .003), and ibuprofen (P less than .03) were found to be positively associated with cataracts; triamterene (P less than .05) had a negative association, indicating a protective relationship. Aspirin was not shown to have a protective effect on reported cataracts.

Age Factors↗

Epidemiology of intermittent claudication: evaluation of risk factors.

Information from a geriatric health screening programme (Dunedin Program) was used to study the prevalence and risk factors predisposing to intermittent claudication (IC) in 1704 ambulatory elderly subjects. Risk factors studied included reported symptoms and diseases, mediation use, haematological and biochemical findings. The prevalence of IC reported by Dunedin participants was 14.1% for women and 14.4% for men. There was a positive relationship between IC and the number of other diseases and symptoms reported (P less than 0.0001). Serum glucose, cholesterol, and triglycerides were significantly higher in subjects reporting IC. Systolic blood pressure was higher in men and women reporting IC, but no significant relationship was observed with diastolic blood pressure.

Aged↗

Angiotensin converting enzyme inhibitors: animal experiments suggest a new pharmacological treatment for alcohol abuse in humans.

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.

Alcohol Drinking↗

Ethanol as a reinforcer for rats: factors of facilitation and constraint.

This review examines some particular approaches that have been used to investigate factors that facilitate or constrain the self-administration of ethanol by rats. A technique for increasing ethanol self-administration in rats, the prandial drinking method, was examined and the effect of body-weight reduction on drug intake was discussed. Emphasis was placed on how ethanol intake may be controlled by processes in addition to the direct pharmacological actions of the drug in the CNS. These processes may be physiological. Evidence was presented for a relationship between activity in the renin-angiotensin system and the self-administration of ethanol. These processes may also be environmental. Using the place-conditioning technique, demonstrations were presented of how the context or situation in which ethanol is experienced may determine whether preference or aversion for the drug develops. Such a diversity in the factors that can potentially control ethanol intake may complicate the identification of the causes of alcohol abuse, but this same diversity also holds out greater hope that manipulations may be found to reduce excessive drinking in humans.

Alcohol Drinking↗

Area postrema and alcohol: effects of area postrema lesions on ethanol self-administration, pharmacokinetics, and ethanol-induced conditioned taste aversion.

An investigation was carried out to test the hypothesis that the area postrema (AP) may detect ethanol as a blood-borne toxin and thereby mediate aversive postingestinal effects of the drug. These aversive effects in turn may impose an upper limit on the amount of drug that can be consumed. In Experiment 1 rats had continuous access to water and a 4% ethanol solution. Animals with AP lesions drank more ethanol than sham-operated controls. No differences in drug disposition or metabolism were found when these rats were injected with ethanol and blood ethanol levels were measured. If the AP lesions resulted in increased ethanol drinking because of a reduction in the aversive effects of the drug, then the lesions might also be expected to attenuate a conditioned taste aversion induced by ethanol. In Experiment 2, groups of lesioned and sham-operated rats drank a novel tasting fluid and then were given i.p. injections of ethanol (0.9, 1.2, or 1.6 g/kg) or vehicle. Similar degrees of aversion to the taste of the fluid developed in both the lesioned and the sham-control groups. Since the AP lesion did not result in the attenuation of the ethanol-induced conditioned taste aversion, it was suggested that the AP may not mediate the aversive consequences of ethanol and that the increased ethanol self-administration observed in Experiment 1 may be due to other effects of the lesion.

Alcohol Drinking↗

Meprobamate use in the elderly. A report from the Dunedin program.

Meprobamate use was studied in an ambulatory elderly population in Dunedin, Florida. All participants taking this medication were mailed a questionnaire concerning their pattern of use. From 2,278 subjects, 30 (1.3%) reported the use of this drug. The average age of participants using this drug was 81.3 years. Five participants began using the drug over 27 years ago and over one-half of the respondents reported using the drug on a regular basis for over 10 years. With this type of history of meprobamate use, one might expect to encounter a large number of patients in the future who, in a similar manner, have been using benzodiazepines for many decades.

Aged↗

Catheter-mediated electrical ablation: the relation between current and pulse width on voltage breakdown and shock-wave generation.

Voltage waveform breakdown is characteristic of barotraumatic shock-wave generation during electrical catheter ablation of cardiac arrhythmias. The purpose of this investigation was to avoid barotrauma by defining, in vitro, the limits of pulse amplitude and pulse width for rectangular constant-current pulses that do not result in voltage breakdown and subsequently to determine what pulsing frequency is safe for use when high-energy trains of pulses are used. Electric pulses were delivered with a variable waveform modulator with a wide dynamic range and bandwidth capable of delivering pulses of 30-10,000-mu sec duration with amplitudes of up to 25 A. Cathodal pulses were delivered to a 6F catheter immersed in fresh anticoagulated bovine blood warmed to 37 degrees C to stimulate the milieu of a catheter in the chambers of the human heart. The maximum pulse amplitude that could be delivered without incurring voltage waveform breakdown varied inversely with pulse duration. Pulses of 30 mu sec broke down at currents above 24 A (2,500 V). Pulses of 10,000-mu sec duration broke down at 1 A (250 V). The maximum safely delivered energy for a single pulse was 2.5 J for pulses of 80-120 mu sec. Peak power for single pulses was maximum at 50-55 kW with 30-50-mu sec pulses. Charge delivery for single pulses was maximized at 9 mC with long, 10,000-mu sec duration pulses. To deliver an electrical pulse with energy significantly greater than 2.5 J without incurring voltage breakdown, trains of pulses were delivered where each pulse in the train had previously been shown to be free of voltage breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of zinc supplementation on the development of cardiovascular disease in the elderly.

Supplemental zinc intake by an ambulatory elderly population was examined. Health questionnaire, electrocardiogram, laboratory, and medication use data from a geriatric health screening program were compared for 69 participants who were taking zinc supplements and 1,832 participants who were not taking zinc supplements during 1985. A major purpose of this study was to evaluate whether ingestion of zinc supplements by elderly persons is a risk factor for development of cardiovascular disease. No association between zinc supplementation and increased risk of developing cardiovascular disease was found for the indices examined. More information is needed to resolve the question of whether or not zinc supplementation is a risk factor for the development of cardiovascular disease. It is important that elderly persons be provided information to evaluate the possible risk versus benefit of taking zinc supplements.

Aged↗

Studies of ERA/BHK-21 rabies vaccine in skunks and mice.

ERA rabies vaccine virus grown in BHK-21 13S cells (ERA/BHK-21) and street rabies virus were titrated in mice by intracerebral, intranasal and intramuscular inoculation. Mice were also given undiluted ERA/BHK-21 in baits. Skunks were given undiluted ERA/BHK-21 in baits and by intramuscular, intranasal and intestinal inoculation. Virus neutralizing antibody titers against rabies virus were measured over a three month observation period. The surviving skunks were challenged by intramuscular inoculation with rabies street virus from a skunk salivary gland suspension. When titrated in mice, ERA/BHK-21 had titers of 10(7.0), 10(5.2) and 10(3.9) median lethal doses per mL by the intracerebral, intranasal and intramuscular routes, respectively. All skunks (8/8) inoculated intranasally developed paralytic rabies by 12 days after exposure to ERA/BHK-21 virus. None of the skunks that developed vaccine-induced rabies had infectious virus in the submandibular salivary glands. Vaccine-induced rabies also occurred in 1/8 skunks in the intramuscularly inoculated group and in 1/8 in the intestinally inoculated group. The survival rates of challenged skunks in the various groups were as follows: intramuscular, 7/7; intestinal, 2/7; bait, 0/8; and control, 0/8. These results indicate that ERA/BHK-21 virus has a significant residual pathogenicity in mice and in skunks by some routes of inoculation. Skunks given vaccine intramuscularly were protected against challenge, while those skunks given the vaccine in baits were not.

Administration, Intranasal↗

Intraoperative comparison of sequential-pulse and single-pulse defibrillation in candidates for automatic implantable defibrillators.

Sixteen survivors of cardiac arrest underwent intraoperative comparison of the effectiveness of sequential-pulse and single-pulse defibrillation. Defibrillation was tested alternately with the single-pulse or sequential-pulse technique 10 seconds into an episode of ventricular fibrillation that was induced with alternating current. The sequential-pulse defibrillation technique using truncated exponential pulses was performed with a right ventricular endocardial catheter and a left ventricular epicardial patch electrode. The first pulse was delivered between the right ventricular apical and the superior vena caval electrode on the right ventricular endocardial catheter. The second pulse was delivered between the right ventricular apical electrode and the left ventricular patch electrode 0.2 ms after termination of the first pulse. Single-pulse defibrillation was performed with a standard intracardiac defibrillation system in which a single truncated exponential pulse was delivered across 2 epicardial patch electrodes positioned over the anterolateral right ventricle and the posterolateral left ventricle. During defibrillation threshold determination, voltage and current waveforms were recorded and integrated to determine delivered energy. Average defibrillation threshold leading-edge voltage for the sequential pulse technique was 496 +/- 140 V, compared with 365 +/- 157 V for the single-pulse technique (p less than 0.005). Defibrillation threshold leading-edge current for the sequential-pulse technique was 6.0 +/- 2.3 A, compared with 10.6 +/- 5.1 A for the single-pulse method (p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Enzyme immunoassay for detection of Mycoplasma bovis antigens in bull semen and preputial washings.

A capture enzyme immunoassay was developed for the detection of Mycoplasma bovis antigens in bull semen or preputial washings. IgG prepared from rabbits immunised with M bovis was passively adsorped to 96-well polystyrene plates. This antibody captured M bovis antigens which were then detected by using an IgG preparation from an immunised cow and murine monoclonal antibody to the bovine L-chain conjugated with horseradish peroxidase. The sensitivity of the assay was approximately 200 colour changing units (ccu)/ml and the specificity was excellent in that other species of mycoplasma, ureaplasma or acholeplasma did not react. A blind study of bull semen experimentally contaminated with M bovis detected all specimens with more than 200 ccu/ml.

Animals↗