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Biomedical subjects

J E Jackson

Publications and source records attributed to J E Jackson.

At least 127 records · Page 7Linked to original sources

The effect of nifedipine on cardiopulmonary responses during exercise in normal subjects.

We investigated the effects of a single dose of nifedipine (10 mg orally) on exercise performance during progressive incremental cycle ergometry in nine sedentary normal subjects in a double-blind, placebo-controlled crossover study. Maximum work load after nifedipine (213 +/- 42 watts; mean +/- SD) was less than after placebo (222 +/- 41 watts; p less than 0.05). Maximum oxygen consumption was unchanged. In addition, the drug decreased lactate threshold from 19.7 +/- 4.9 ml O2/min/kg to 15.5 +/- 5.5 ml O2/min/kg (p less than 0.02); gas exchange anaerobic threshold was unaffected. There were higher plasma lactate concentrations at low and intermediate exercise intensities after nifedipine compared with placebo (p less than 0.05). Systolic blood pressure was lower at high work loads (p less than 0.05) and heart rate was higher at low work loads (p less than 0.05) after nifedipine. We conclude that the short-term administration of nifedipine limits peak performance and increases plasma concentration of lactic acid in normal subjects. One or more of the following mechanisms may account for these observations: nifedipine decreases blood flow to skeletal muscle by diverting blood to nonexercising tissues; nifedipine increases catecholamine levels, thereby augmenting lactic acid production; and nifedipine decreases skeletal muscular contractility by selectively impairing fatigue-resistant fibers.

Adult↗

Effects of histamine-2 receptor blockade on lidocaine kinetics.

The hypothesis that the H2-receptor blockers cimetidine and ranitidine have different effects on the disposition of lidocaine, a microsomally metabolized drug dependent on hepatic blood flow for elimination, was tested. Six normal men received lidocaine infusions (2 mg/kg over 10 minutes) and lidocaine levels were determined by HPLC. Lidocaine kinetics were studied in the untreated state (O) and in a double-blind, double-dummy design after 2 days of placebo (P), cimetidine (C, 300 mg every 6 hours by mouth), or ranitidine (R, 160 mg every 12 hours by mouth). Model-independent kinetics were estimated by the statistical moment theory. The steady-state volume of distribution was lower after cimetidine (means +/- SD: O, 156 +/- 39 L; P, 156 +/- 48 L; C, 123 +/- 20 L; and R, 174 +/- 38 L). A trend toward decreased lidocaine clearance after cimetidine was also noted (O, 1011 +/- 140 ml/min; P, 1087 +/- 227 ml/min; C, 886 +/- 214 ml/min; and R, 1143 +/- 225 ml/min). Elimination rate constants were of the same order in all four treatments. Only higher levels of alpha 1-acid glycoprotein appeared to limit the lidocaine steady-state volume of distribution. Cimetidine and ranitidine have distinctly different effects on lidocaine kinetics in normal subjects. The absence of ranitidine effects on the disposition of lidocaine, a high-extraction, high-clearance drug, suggests that H2-receptor blockade may not decrease hepatic blood flow, and that cimetidine impairs drug elimination only by inhibition of hepatic microsomal enzymes. Such interactions are not likely to occur with ranitidine.

Administration, Oral↗

Distribution volume of ethanol as a measure of body water.

We compared the volumes of distribution of intravenous and intragastric ethanol, in a dose of either 7.7 or 11 mmol/kg, to the 3H2O space in anesthetized dogs. The intravenous ethanol space agreed closely with the 3H2O space (y = 0.197 + 0.974x; x axis 3H2O space, r = 0.967, n = 37). After acute saline infusion, changes in both intravenous ethanol and 3H2O spaces reflected accurately the volumes of infused isotonic saline. The determination of intravenous ethanol space could be repeated within 5 h. The intragastric ethanol space overestimated both the 3H2O space and the intravenous ethanol space. Incomplete absorption of ethanol from the gastrointestinal tract was the cause of this observation. In dogs, the intravenous ethanol space provides an accurate measure of body water and of its short changes (a few hours). The intragastric ethanol space overestimates body water in anesthetized dogs because of delayed gastrointestinal absorption.

Animals↗

Passive transfer experiments in amyotrophic lateral sclerosis.

To test the hypothesis that a serum factor might play a role in the pathogenesis of amyotrophic lateral sclerosis, whole plasma obtained by plasmapheresis from patients with the disease was injected daily intraperitoneally into mice for periods of up to three months. Similar experiments were carried out with an isolated immunoglobulin fraction. Control experiments were carried out simultaneously. The animals were tested electrophysiologically, and histologic examinations of the brain, spinal cord, and peripheral nerves were performed. No ill effects were noted in the animals, and no neurophysiologic or microscopic abnormalities were detected.

Adult↗

Restriction endonuclease analysis of Leishmania kinetoplast DNA characterizes parasites responsible for visceral and cutaneous disease.

The kinetoplast DNA (kDNA) from promastigotes of Leishmania responsible for Old and New World cutaneous and visceral disease was characterized to determine if species and strains causing similar or different diseases could be identified. Restriction enzymes were used to digest kDNA into fragments that were separated into characteristic banding patterns after electrophoresis in agarose or linear gradient polyacrylamide gels. Hybridization was conducted with a 32P-kDNA probe and kDNA fragments transferred from agarose gels to nitrocellulose paper. Leishmania species causing cutaneous diseases in the New and Old Worlds all had different kDNA digest patterns. Visceralizing Leishmania from the New and Old Worlds also had different kDNA restriction fragment patterns although Leishmania donovani parasites with similar fragment patterns were isolated from several humans from central Kenya. Nucleotide sequences were shared among kDNA networks from L. donovani, Leishmania d. chagasi, Leishmania d. infantum, Leishmania tropica, and Leishmania major as determined by hybridization with a 32P-kDNA probe from L. donovani. However, no hybridization was detected between the L. donovani 32P-kDNA probe and kDNA from Leishmania aethiopica or Leishmania braziliensis panamensis. Leishmania characterization results for the same isolates from the published literature were compared and kinetoplast DNA analysis was found to be one of the most sensitive procedures for species and strain identification.

DNA↗

Heterotopic pancreas obstructing the ampulla of Vater.

Heterotopic pancreas, a developmental anomaly uncommonly noted both during operations and autopsies, is usually described in each instance as an incidental finding. Rarely, ectopic pancreas can cause intra-abdominal hemorrhage or obstruction. We studied a case in which aberrant pancreas located at the ampulla of Vater was found to be the cause of partial obstruction of the common bile duct. Resection of the duodenal papilla and anastomosis of the distal common duct to the duodenum resulted in complete cure. Treatment of the symptomatic patient with heterotopic pancreas demonstrated during gastrointestinal diagnostic examination, and the asymptomatic patient with ectopic pancreas discovered at laparotomy, are discussed.

Ampulla of Vater↗

Assessment of the antihypercholesterolemic drug, Probucol, in benign prostatic hyperplasia.

Seventy patients were administered either Probucol, an anti-cholesterol agent or a placebo in a double blind manner for a period of 1 year in an effort to assess the effectiveness of this agent in treating benign prostatic hyperplasia. Sensation of incomplete voiding and peak and mean voiding flow rates showed a trend which indicated a therapeutic effect, however, this effect was comparable for both placebo and the drug group. This is interpreted as indicating the effectiveness of standard urologic therapy, and double blind trials are therefore needed in assessing different agents for the medical management of benign prostatic hyperplasia.

Cholesterol↗

Cimetidine protects against acetaminophen toxicity.

Generally, acetaminophen (APAP) overdoses with elimination half-lives over 4 hr. sustain liver damage. In the following cases, cimetidine (C) seems to have protected against APAP toxicity. An 18 yr. old, 64 kg female smoker presented 6 hr. after taking 10Rg APAP, 1200+ mg C, and small amounts of flurazepam and Sleepeze (methaprilene + scopolamine). Three plasma APAP levels (by HPLC) revealed an elimination half-life of 4.4 hr. C did not interfere with the APAP assay. Despite the long half-life in a patient with microsomal enzymes induced by smoking, no evidence of hepatotoxicity developed. A month later, the same patient overdosed with APAP alone. Three plasma levels revealed a 3.3 hr. half-life. Lack of toxicity in the presence of a long elimination half-life may indicate a protective action of C in APAP overdoses.

Acetaminophen↗

Serum ethyl alcohol levels and osmolal gaps.

We compared 56 paired measurements of osmolal gaps and serum ethyl alcohol levels in 15 anesthetized dogs. We then repeated these comparisons after correcting the osmolal gaps for the preceding (the administration of ethyl alcohol) difference between measured and calculated osmolalities. No statistical differences were observed between ethyl alcohol levels and either uncorrected or corrected osmolal gaps. However, uncorrected osmolal gaps differed from ethyl alcohol levels by less than 5 mmol/L in 39.3% of the measurements and by more than 10 mmol/L in 19.6% of the measurements. Corresponding percentages for corrected osmolal gaps were 94.6 and 0 respectively. Thus uncorrected osmolal gaps offer a rough screening test, whereas corrected osmolal gaps offer accurate predictions of serum ethyl alcohol levels.

Animals↗

Cimetidine decreases theophylline clearance.

This study tested the hypothesis that cimetidine decreases theophylline clearance. Aminophylline (6 mg/kg) was administered intravenously both before and after cimetidine treatment in 5 healthy adults. Cimetidine (300 mg) was administered orally every 6 h for 2 days before and 18 h after the aminophylline dose. Plasma samples were collected before and for 24 h after each aminophylline dose, and theophylline concentrations were determined by an enzyme-mediated immunoassay technique. Cimetidine significantly decreased theophylline clearance, mean decrease, 39% (3.85 +/- 0.27 L/h control versus 2.34 +/- 0.23 L/h with cimetidine treatment, p less than 0.002). The apparent volume of distribution was unchanged (p greater than 0.5), whereas the elimination rate constant was significantly decreased by a mean of 42% (control, 0.091 +/- 0.013 h-1 versus 0.053 +/- 0.007 h-1 with cimetidine treatment, p less than 0.005). This corresponded to an average increase in elimination half-life of 73% (range, 50 to 97%). Cimetidine probably slowed theophylline elimination by relatively nonspecific inhibition of the hepatic microsomal mono-oxygenase system. This effect may produce clinically significant changes in serum theophylline concentrations.

Administration, Oral↗

Clinical pharmacology of sulphonylurea hypoglycaemic agents: part 1.

The sulphonylureas are drugs of limited efficacy with fairly frequent, although usually reversible, adverse effects. Being highly protein bound, these drugs are subject to potential displacement interactions, which when combined with inhibition of their elimination, may result in profound hypoglycaemia. Due to hepatic metabolism and renal excretion of the parent drug and/or active metabolites, these agents are contraindicated in patients with liver or kidney disease. Oral hypoglycaemic agents are frequently used in elderly patients with limited vision and no dependable relatives, who cannot give themselves insulin. It is these patients--elderly, living alone in poor circumstances, often on several other medications, and possibly malnourished--who are at greatest risk for catastrophic hypoglycaemia with these drugs. Long acting agents like chlorpropamide and glibenclamide should be avoided in the elderly and in patients with irregular eating habits. Diet and exercise remain the primary modes of therapy of non-insulin-dependent diabetes mellitus. With careful patient selection and attention to drug and disease interactions, the sulphonylureas may be a useful adjunct to diet in treating a small proportion of insulin-resistant (so-called adult onset) diabetics. Patients most likely to respond to sulphonylureas are over 40 years old, mildly to moderately obese, have had diabetes for less than 5 years, and have never exhibited ketosis. There is no indication for simultaneous use of sulphonylureas and insulin. With both insulin and the oral hypoglycaemics alcohol is the agent most commonly implicated in lethal interactions.

Diabetes Mellitus↗

Reduced dose of Rho(D) immune globulin following induced first-trimester abortion.

A double-blind study of women after first-trimester abortion supports the efficacy of low-dose Rho(D) immune globulin (human) in the prevention of Rh sensitization. Twenty-seven per cent of patients demonstrated a fetomaternal blood leak based on Kleihauer-Betke stains. In follow-up testing, the percentage of positive titers and the absolute titer of detectable antibody at various intervals were related to the dose of administered immune globulin. This study confirmed the possible risk of sensitization in Rh-negative postabortal women and suggests the practical use of single low-dose immune globulin preparations in prevention.

Abortion, Induced↗