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Biomedical subjects

T Johnson

Publications and source records attributed to T Johnson.

At least 217 records · Page 12Linked to original sources

Long-term efficacy of oral pirmenol in suppressing ventricular premature depolarizations.

Pirmenol is an investigational type 1A antiarrhythmic drug the long-term efficacy of which has not been fully determined. Therefore the long-term efficacy of oral pirmenol in suppressing ventricular premature depolarizations (VPDs) was assessed in an open-label, dose-titration study. Twelve patients (eight men and four women; mean age 57 +/- 12 years) were treated for 24 to 36 months (mean 33 +/- 4). Seven had structural heart disease (three valvular heart disease, two ischemic heart disease, and two hypertensive heart disease) and five did not. The mean left ventricular ejection fraction was 0.63 +/- 0.13. Exclusion criteria included less than 30 VPDs/hr, greater than 15 beats of ventricular tachycardia (VT), or prior failure of more than two antiarrhythmic drugs. Drug efficacy was assessed by 24-hour ambulatory ECG monitoring performed every 3 months during the first year, every 4 months during the second year, and at 6-month intervals during the third year. The mean hourly frequency of VPDs during the placebo phase was 732 +/- 608. Seven patients (58%) were treated successfully with effective (greater than 75%) long-term suppression of VPDs. Two patients (17%) had a partial response with effective suppression of VPDs for the first 16 months and 5 months of treatment, respectively. Three patients failed to show consistent suppression of VPDs while receiving pirmenol. The daily dose of pirmenol ranged from 200 to 500 mg (mean 317 +/- 94 mg at the beginning of the study and 375 +/- 97 mg at the end). No proarrhythmic effects were identified during long-term treatment, and none of the patients withdrew from the study prematurely.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Radiation sensitivity and DNA repair in Caenorhabditis elegans strains with different mean life spans.

The sensitivities to three DNA damaging agents (UV and gamma-radiation, methyl methanesulfonate) were measured in four recombinant inbred (RI) strains of Caenorhabditis elegans with mean life spans ranging from 13 to 30.9 days, as well as in the wild-type strains used to derive these RI's. Sensitivities at several stages in the developmental cycle were tested. There were no significant correlations between mean life span and the lethal effects of these 3 agents. Excision of two UV-radiation-induced DNA photoproducts was also measured. Long-lived strains were no more repair competent than shorter-lived strains. These data indicate that DNA repair plays at best a minor role in the aging process of C. elegans.

Animals↗

Indium-111 platelet kinetics in patients with diabetes mellitus.

We performed in vitro aggregation and indium-111 labeled platelet kinetic and biodistribution studies in seven patients with diabetes mellitus and in five control subjects. All subjects were male. All diabetic patients were poorly controlled at the time of study with blood glucose greater than 140 mg % and hemoglobin A1c greater than 10%. In vivo kinetic and biodistribution studies were performed following reinjection of autologous platelets labeled with indium-111 oxine in a dose of approximately 50 microCi (42-67 microCi). Images obtained at 4 and 24 h were computer-analyzed to determine splenic and hepatic uptake, and platelet survival times were calculated using four mathematical models. Unexpectedly, diabetic patients with fewer vascular complications tended to have shorter platelet survival times than patients with advanced vascular disease. However, no significant differences were observed between diabetic and control groups for any of the parameters of platelet function evaluated.

Blood Platelets↗

Antitussive properties of inhaled bronchodilators on induced cough.

We have studied the antitussive effects of two anticholinergic agents, oxitropium bromide (200 micrograms) and ipratropium bromide (80 micrograms), and a combined beta-agonist and anticholinergic preparation containing fenoterol hydrobromide (200 micrograms) and ipratropium bromide (80 micrograms), in 16 normal and ten asthmatic volunteers in a double-blind, randomized, placebo-controlled crossover trial. Cough was induced by inhalation of ultrasonically nebulized distilled water and hypotonic saline solution. All treatments significantly reduced the cough response to inhaled distilled water aerosol when compared with placebo (p less than 0.001). There was no difference between oxitropium bromide and ipratropium bromide (p greater than 0.05), but the combination preparation displayed a greater antitussive effect than either oxitropium bromide (p less than 0.05) or ipratropium bromide (p less than 0.025). Cough frequencies in response to hypotonic 0.18 and 0.32 percent saline aerosol were lower than those obtained with distilled water (p less than 0.005) for all treatments. Asthmatic patients coughed less frequently than normal volunteers in response to all solutions when placebo was given (p less than 0.05), but there is no evidence to suggest that the response to treatment was different in the two groups. Our results suggest that inhaled anticholinergic bronchodilators alone or in combination with beta 2-adrenergic agonists might be effective in the treatment of pathologic cough.

Administration, Inhalation↗

Effect of switching diets on growth and digesta kinetics of cattle.

An approach was developed for describing live weight gain and the contribution of wet gut fill gain to live weight gain in growing cattle. In a continuous growth study, energy densities of winter:spring diets were used to define four treatment groups of cattle. Concentrates and forages were the major ingredients of higher and lower energy-density diets, respectively. Cattle receiving high and low energy sequences (HH and LL) were designated as control groups and were compared with two change-over groups: high to low (HL) and low to high (LH). Switches involved simultaneous changes in several feed characteristics. Every 2 wk for 4 mo, 39 heifers and 19 steers were weighed. Switching young cattle to another diet affected growth during the 2 wk immediately after the switch. After being switched to the lower energy-density diet (i.e., pasture), HL and LL groups lost (P less than .001) from 3.5 to 27.4 kg in both fed and fasted weight. Neither fed nor fasted weights of HH and LH steers changed during the switch to the higher energy-density diet (i.e., concentrates); HH and LH heifers continued to gain (P less than .001). Throughout the remainder of the study, growth rates of cattle were similar for HH and LH groups and for HL and LL groups. In spring, cattle consuming concentrate diets (HH and LH) had greater fill (P less than .001) than pasture-fed contemporaries (HL and LL). Less frequent measurement of growth characteristics would have obscured important facets of growth. A loss of weight followed by continuous gain is not equivalent to a reduced growth rate.

Animal Nutritional Physiological Phenomena↗

Responses of dairy cattle to long-term and short-term supplementation with oral selenium and vitamin E1.

In a two-lactation-gestation cycle experiment, 152 Holstein cows with low serum Se and vitamin E were fed total mixed rations and assigned at parturition to four groups (1, control; 2, 500 IU vitamin E/d; 3, 2 mg Se/d; 4, 500 IU vitamin E plus 2 mg Se/d). Supplements were not fed during dry periods. Serum Se and vitamin E were increased within 1 mo by oral supplements. Maximal mean serum Se in cycles 1 (67 ng/ml at 7 mo) and 2 (74 ng/ml at 4 mo) occurred in groups 3 and 4, respectively. Maximal mean serum vitamin E in cycle 1 (3.3 micrograms/ml at mo 8) and 2 (3.03 micrograms/ml at mo 2) occurred in groups 4 and 2, respectively. Selenium treatment of the dams increased Se in colostrum and in serum of presuckle calves. Vitamin E supplementation of dams did not affect vitamin E in serum of presuckled calves. Reproductive performance was not affected by supplement. In an 8-wk study, 24 lactating cows with low serum Se were assigned (6/group) to 0, 2.5, 5, and 10 mg supplemental Se/d. Maximal mean serum Se concentrations of 23, 56, 71, and 79 ng/ml were attained by wk 4 in the above respective groups. These data indicate that 2 to 2.5 mg supplemental Se/cow per d were inadequate for desirable serum Se concentrations and support recent changes in allowed Se supplementation for dairy cattle.

Administration, Oral↗

The role of folylpolyglutamate synthetase and gamma-glutamyl hydrolase in altering cellular folyl- and antifolylpolyglutamates.

The metabolic products of methotrexate differ in hepatocytes and hepatoma cells; the primary products are 7-hydroxymethotrexate in hepatocytes and the polyglutamate derivatives in hepatoma cells. The rate of glutamylation is approximately 5-fold greater in hepatoma cells than hepatocytes under comparable conditions and the polyglutamate products in the hepatoma cells consist of longer chain length tri- and tetraglutamate derivatives, whereas the hepatocytes favor the diglutamate derivative. Extracts of cultured hepatocytes have approximately half the folylpolyglutamate synthetase and three times as much gamma-glutamyl hydrolase as the hepatoma cells. A further difference is that methionine inhibits glutamylation in hepatocytes whereas it can cause a marked stimulation (five- to seven-fold) in hepatoma cells. The rate of glutamylation of methotrexate in intact hepatoma cells is strongly dependent on the culture conditions and can be enhanced as much as five-fold in dividing cultures or by removing folates from the cells. These changes may be in part caused by the fact that the folylpolyglutamate synthetase is nearly doubled in both growing cultures and in folate lacking cells. The treatment of human liver in vivo or rodent hepatic cells in vivo and in vitro with methotrexate causes a reduction in the folate pools. Data presented in these studies show that the activity of gamma-glutamyl hydrolase in cells can be enhanced by prior exposure to methotrexate. Thus, methotrexate could cause a loss in cellular folylpolyglutamates by enhancing their rate of cleavage to folylmonoglutamates.

Animals↗

Metal chelates as urographic contrast agents for magnetic resonance imaging. A comparative study.

Paramagnetic metal chelates including Fe-EDTA, Fe-CDTA, Fe-DTPA, and Gd-DTPA were compared as intravenous urographic contrast agents for magnetic resonance (MR) imaging in rats. Each compound, administered intravenously at three different doses (0.05, 0.1, and 0.2 mmol./kg.), was rapidly excreted through the kidneys yielding renal signal enhancement between 5 min. and 50 min. after injection. Gd-DTPA was most effective vor the enhancement of the renal parenchyma and pelvis. Lesser enhancement was achieved by administration of Fe-CDTA followed by Fe-EDTA and Fe-DTPA. Enhancement of skeletal muscle and liver parenchyma could not be achieved with any of the compounds included in this study. We conclude that the iron chelates mentioned above are less effective as urographic agents for MR imaging than Gd-DTPA.

Animals↗

The preservation of urine samples for determination of renal stone risk factors.

A preservation technique for urine specimens before determination of stone risk factors was evaluated. The purpose of these experiments was to prove the effectiveness of the preservatives used to prevent changes in the concentrations of those constituents measured. Measured concentrations in fresh specimens were compared with those in the same specimens after storage with the preservatives. Refrigeration at 4 degrees C up to five days was appropriate in a laboratory setting, as no significant changes in urinary concentrations occurred. Refrigeration, however, did not offer a convenient method for shipping. Chemical preservation was found to be an effective alternative to refrigeration. Thymol prevented changes in concentration of pH, citrate, uric acid, sulfate, sodium, potassium, and cyclic AMP, while a mixture of hydrochloric (HCl) acid and boric acid prevented changes in calcium, magnesium, phosphorus, oxalate, ammonium, and creatinine. Thus, the addition of thymol or HCl/boric acid to urine specimens will prevent significant changes in the concentrations of stone risk factors.

Boric Acids↗

Inhibition of artificially induced cough in man by bronchodilators.

1. The antitussive properties of bronchodilators were evaluated in a total of 47 normal volunteers. 2. Cough was induced by inhalation of ultrasonically nebulized solutions of distilled water and hypotonic saline. 3. Inhaled fenoterol hydrobromide (360 micrograms; 20 volunteers) and inhaled ipratropium bromide (72 micrograms; 14 volunteers) both significantly reduced couch compared with placebo (P less than 0.01). Oral salbutamol sulphate (4 mg; 11 volunteers) and oral pirenzepine hydrochloride (50 mg; 14 volunteers) had lesser effects. 4. Cough inhibition correlated with a small but statistically significant degree of bronchodilatation as measured by specific airway conductance (sGaw) and forced expiratory volume in one second (FEV1) in six normal subjects studied with each treatment in a placebo controlled, double blind study (r = 0.67, P less than 0.001). 5. Small reductions in airway tone are associated with a reduced cough response elicited by inhaled ultrasonically nebulized distilled water.

Adolescent↗

Effects of increasing intercellular resistance on transverse and longitudinal propagation in sheep epicardial muscle.

Propagation in cardiac muscle is faster in the longitudinal than in the transverse axis of the cells. Yet, as a result of the larger upstroke velocity of action potentials propagating transversely, it has been suggested that longitudinal propagation is more vulnerable to block. To study the relation between conduction velocity and maximal upstroke velocity (Vmax), as well as the time course of conduction delay and block in the transverse vs. longitudinal direction, thin square pieces of sheep epicardial muscle were superfused with the cellular uncoupler heptanol (1.5 mM). Action potentials were recorded with microelectrodes at opposite corners of the preparation while stimulating alternately in the longitudinal or transverse direction with bipolar electrodes located at contralateral corners. In all cases, block occurred more promptly for transverse than for longitudinal propagation. The decrease in conduction velocity was greater than expected for Vmax decay and, in some cases, Vmax increased while conduction velocity decreased. In the presence of high grade conduction impairment, foot potentials appeared and the upstrokes became "notched." We conclude that when intercellular coupling is impaired, transverse propagation is more vulnerable to block, and need not be dependent on changes in Vmax.

Action Potentials↗

Neurohumoral activation during exercise in congestive heart failure.

Neurohumoral factors were assessed in 14 subjects with chronic, stable New York Heart Association functional class II or III congestive heart failure and nine comparably aged normal subjects at rest and during moderate (50 W) and strenuous (100 W) upright exercise. Heart failure was associated with elevated plasma renin activity and plasma antidiuretic hormone (ADH) concentrations at rest. However, plasma renin activity almost doubled (from 4.7 +/- 0.6 to 8.4 +/- 1.1 ng/ml per hour) during strenuous exercise in subjects with heart failure, and changed only minimally in normal control subjects. Plasma ADH concentration did not change during exercise in the presence of heart failure, but rose in normal subjects during strenuous exercise to levels comparable to those of subjects with heart failure. Similar plasma osmolality values were present in both groups. Circulating norepinephrine concentrations were insignificantly elevated by heart failure both at rest and during exercise, and plasma epinephrine concentrations were similar. These findings suggest independent neurohumoral activation during exercise in the presence of congestive heart failure, with predominant activation of the renin-angiotensin-aldosterone axis.

Adult↗

Alcohol and drug use among "street" adolescents.

Studies of adolescent alcohol use typically sample intact high school populations. This study assessed "street" adolescents alienated from the mainstream educational system. Despite recent optimism regarding adolescent substance use, these respondents showed considerable alcohol consumption, drinking to get drunk, and problems. The major correlates of substance abuse were "personal" drinking motives, expectancies of alcohol effects and peer behavior. Thus, adolescents who would not appear in typical studies showed much stronger alcohol involvement than the general population, with individual differences best accounted for by attitude variables relevant to a "stress-vulnerability" approach to substance abuse.

Adolescent↗