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Biomedical subjects

J H Saunders

Publications and source records attributed to J H Saunders.

At least 37 records · Page 2Linked to original sources
PubMed1985

Pharmacokinetics of inhaled methyl chloride (CH3Cl) in male volunteers.

Six volunteers, 25-41 years of age, were exposed for 6 hr on separate days to 50 and 10 ppm of CH3Cl. Blood and expired air CH3Cl concentrations reached an apparent plateau during the first hour of the exposure and were proportional to the exposure concentration. Consistent with previous reports, the volunteers could be separated into two discrete groups based on the differences observed in their blood and expired air CH3Cl concentrations. Both groups eliminated CH3Cl rapidly once the exposure was terminated, but CH3Cl was eliminated more rapidly by those volunteers with the lower blood and expired air CH3Cl concentrations. The existence of these two groups can be explained by a twofold difference in the rate at which they metabolized CH3Cl; however, this difference is of questionable toxicological significance. Urinary excretion of the putative metabolite S-methyl cysteine was not related to the exposure; thus, it is not a valid means of monitoring occupational exposure to CH3Cl.

Adult↗
PubMed1984

Chlorpyrifos: pharmacokinetics in human volunteers.

The kinetics of chlorpyrifos, an organophosphorothioate insecticide, and its principal metabolite, 3,5,6-trichloro-2-pyridinol (3,5,6-TCP), were investigated in six healthy male volunteers given a single 0.5 mg/kg po and, 2 or more weeks later, a 0.5 or 5.0 mg/kg dermal dose of chlorpyrifos. No signs or symptoms of toxicity or changes in erythrocyte cholinesterase were observed. Plasma cholinesterase was depressed to 15% of predose levels by the 0.5 mg/kg po dose but was essentially unchanged following the 5.0 mg/kg dermal dose. Blood chlorpyrifos concentrations were extremely low (less than 30 ng/ml), and no unchanged chlorpyrifos was found in the urine following either route of administration. Mean blood 3,5,6-TCP concentrations peaked at 0.93 micrograms/ml 6 hr after ingestion of the oral dose and at 0.063 micrograms/ml 24 hr after the 5.0 mg/kg dermal dose. 3,5,6-TCP was cleared from the blood and eliminated in the urine with a half-life of 27 hr following both the po and dermal doses. An average of 70% of the po dose but less than 3% of the dermal dose was excreted in the urine as 3,5,6-TCP; thus only a small fraction of the dermally applied chlorpyrifos was absorbed. Chlorpyrifos and its principal metabolite were rapidly eliminated and therefore have a low potential to accumulate in man on repeated exposures. Based on these data, blood and/or urinary 3,5,6-TCP concentrations could be used to quantify the amount of chlorpyrifos absorbed under actual use conditions.

Administration, Oral↗
PubMed1984

Pharmacokinetics of picloram in male volunteers.

The fate of picloram (4-amino-3,5,6-trichloropicolinic acid), an active ingredient in TORDON brand herbicides, was defined in 6 healthy male volunteers following single po doses of 5.0 and 0.5 mg/kg, and a dermal dose of 2.0 mg/kg. Picloram was administered orally as the sodium salt in grape juice. The dermal dose was applied to the volunteers' backs as the free acid dissolved in ethanol. The data indicate picloram was rapidly absorbed from the gastrointestinal tract (t1/2 = 20 min) and rapidly excreted unchanged in the urine. Over 90% of the po dose was recovered as unchanged picloram in the urine excreted through 72 hr; most of the dose (greater than 75%) was excreted within 6 hr and the remainder was excreted with an average half-life of 27 hr. By comparison picloram was slowly absorbed through the skin (t1/2 = 12 hr) and, based on the quantity of picloram excreted in the urine, only a small fraction (0.2%) of the picloram applied to the skin was absorbed. These data indicate that picloram because of its rapid excretion has a low potential to accumulate in man during repeated or prolonged exposures. In addition, picloram was poorly absorbed through human skin and it is unlikely that acutely toxic quantities will be absorbed by this route.

Administration, Oral↗
PubMed1984

Kinetics and metabolism of inhaled methyl chloroform (1,1,1-trichloroethane) in male volunteers.

The kinetics of inhaled methyl chloroform (MC) and its principal metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA), were defined in six healthy male volunteers following single 6-hr exposures of 350 and 35 ppm. Blood and expired air MC concentrations were proportional to the exposure concentration and indicated that about 25% of the MC inhaled during the 6-hr exposure was absorbed. Elimination of MC was triexponential with half-lives estimated as 44 min, 5.7 hr, and 53 hr for the initial, intermediate, and terminal phases. Over 91% of the absorbed MC was excreted unchanged via the lungs, 5-6% was metabolized and excreted as TCE and TCA, and less than 1% remained in the body after 9 days. Urinary TCE and TCA excretion was extremely variable and indicated that urinary TCE and TCA measurements provide at best only a rough estimate of the exposure. These data suggest that the kinetics of MC in man are essentially first order at or below the current TLV of 350 ppm. Based on a comparison of the blood MC levels and amounts of MC metabolized, the rat is a better model than the mouse to predict the toxicity of MC in man.

Adult↗
PubMed1982

Cholecystoduodenocolic fistula following abdominal trauma.

A case of cholecystoduodenocolic fistula following trauma is reported. It is unusual in that the majority of such fistulas are seen in relation to gallstones. The patient was managed initially by total parenteral nutrition and drainage followed by successful operation.

Abdominal Injuries↗
PubMed1981

Effect of pentagastrin on histamine output from the stomach in patients with duodenal ulcer.

The role of histamine in acid secretion is controversial. Improvements in the techniques of histamine assay allow a better assessment of the relationship of histamine to acid secretion. Patients with duodenal ulcers were studied to determine the mucosal histamine responses to pentagastrin stimulation to relate the appearance of histamine in the gastric juice to acid production during stimulation, and to detect changes in the plasma histamine concentration during pentagastrin stimulation. There was a mean 27% fall (range 0-60%) in mucosal histamine concentration after pentagastrin. The output of histamine into gastric juice closely paralleled acid output in peak output acid duration. The histogram profiles of acid and histamine were similar in shape. In contrast with previous studies, plasma histamine concentration was found to rise during peak acid secretion (mean rise 65%). There was no relationship between initial mucosal histamine concentration and acid secretion or maximal gastric juice histamine. The association of histamine and gastric acid release found in these studies was so close that a functional relationship may be presumed. Our data are compatible with the hypothesis that pentagastrin acts on the parietal cell indirectly by causing histamine release in the gastric mucosa, which in turn releases acid from the parietal cells.

Duodenal Ulcer↗
PubMed1981

Effect of cimetidine on the amounts of histamine in the gastric mucosa of patients with gastric or duodenal ulcers.

Measurements were made of the amounts of histamine extracted from patients with peptic ulcer disease and control subjects suffering from various gastrointestinal diseases. Patients with duodenal ulcer, gastric ulcer, or recurrent duodenal ulcer after proximal gastric vagotomy often had less gastric mucosal histamine than did normal controls. Cimetidine therapy increased the amounts of the histamine to above control levels, presumably by suppression of output. It is concluded that endogenous amounts of histamine reflect the pathogenic states in the gastric mucosa of patients with peptic ulcer diseases. Cimetidine, as does vagotomy, increases the amount of gastric mucosal histamine. These findings suggest that the increase in mucosal histamine with cimetidine is not due to activation of histamine methyl transferase, but rather to suppression of histamine output into the gastric juice.

Adult↗
PubMed1981

Effects of two histamine H2-receptor blocking drugs on basal levels of gonadotrophins, prolactin, testosterone and oestradiol-17 beta during treatment of duodenal ulcer in male patients.

In a study of 51 male patients with duodenal ulcer, treatment with cimetidine was accompanied by an increase in basal levels of serum testosterone. Treatment with ranitidine, a new histamine H2-receptor antagonist, produced no such effect. It is concluded that cimetidine had antiandrogenic activity in man which is separate from the histamine H2-receptor blocking activity.

Adult↗
PubMed1981

Ranitidine in the treatment of duodenal ulceration.

In a randomized, double-blind, endoscopically controlled clinical trial, 40 patients with duodenal ulcer were treated with either ranitidine (320 mg/day) or cimetidine (800 mg/day) for 28 days. The rate of healing of the ulcers (ranitidine, 78%, cimetidine, 45%) did not differ significantly in the two treatment groups. In a subsequent 'open' study, ranitidine (150 mg twice daily) healed the ulcers of 79% of 19 patients treated for 28 days. Treatment with ranitidine was not associated with significant adverse reactions and had no lasting effect on gastric secretory capacity. Whereas basal levels of serum testosterone rose significantly during treatment with cimetidine, no such increase was observed during treatment with ranitidine. We conclude that ranitidine can effectively and safely heal duodenal ulcers.

Adult↗
PubMed1981

Clinical and endocrine aspects of treatment with ranitidine.

Ranitidine has been shown to heal the majority of duodenal ulcers during treatment with 300 or 320 mg daily for 4 to 8 weeks. Twice-daily dosage improved compliance. Subsequent maintenance treatment with ranitidinie, 150 mg at night prevented relapse in the majority of patients during 6-months' follow-up. Ranitidine did not appear to have any anti-androgenic effects.

Administration, Oral↗
PubMed1980

Serum trypsin concentration and pancreatic trypsin secretion in insulin-dependent diabetes mellitus.

Fasting serum trypsin concentration and pancreatic trypsin output, stimulated by secretin and cholecystokinin-pancreozymin, were measured in 18 patients with insulin-dependent diabetes, to assess a possible correlation between these two indices of exocrine pancreatic function. Serum trypsin concentration was subnormal in 13, and pancreatic trypsin output was decreased in 14 patients, but there was no significant correlation between the two measurements. There was no correlation between serum trypsin and residual beta cell function measured by plasma C-peptide immunoreactivity (CPR). After an interval of four years serum trypsin measurements were repeated in 11 subjects. All individual trypsin levels were lower than the previous results, the difference being highly significant (t = 9.0; p < 0.001). Serum trypsin concentration therefore represents a qualitative index of reduced exocrine pancreatic function in diabetes, but has no value in quantitating the degree of deficiency.

Adolescent↗
PubMed1980

Ocular penetration of cefazolin in humans and rabbits after subconjunctival injection.

We determined the clinical potential of cefazolin by assaying aqueous samples for levels of aqueous penetration of cefazolin in humans and rabbits after subconjunctival injection. Cefazolin is a broad spectrum antiotic that appears to penetrate aqueous humor in bactericidal concentrations after subconjunctival injection and may serve as a useful alternative in patients sensitive to other antibiotics.

Animals↗
PubMed1980

Monooxygenase activity of human liver in microsomal fractions of needle biopsy specimens.

1 Methods are described for the determination of mixed function oxidase activity in microsomal fractions from percutaneous needle biopsies of human liver. 2 Activities of needle biopsy samples were comparable with those of wedge biopsy sample obtained at laparotomy from different subjects. 3 Although cytochrome P-450 content of liver from rat and man was similar, human AHH activity was only 10% of that in the rat. 4 In biopsies with preserved hepatic architecture, AHH activity and cytochrome P-450 content showed a significant positive correlation. 5 Cigarette smoking significantly increased both AHH activity and turnover number, but not cytochrome P-450 content, of biopsies with normal architecture. 6 The presence of liver disease caused a significant decrease in AHH activity and cytochrome P-450 content.

Animals↗
PubMed1980

Ursodeoxycholic acid therapy and biliary lipids--a dose-response study.

The effects of four different doses of ursodeoxycholic acid (250, 500, 750, and 1000 mg daily) on biliary lipids were studied in 24 patients with radiolucent gallbladder stones. There was a significant increase in the proportion of ursodeoxycholic acid in bile after all doses, being greatest with 750 and 1000 mg daily. Unsulphated lithocholic acid was also increased in the bile after therapy, while the other major bile acids were reduced. The cholesterol content of bile was reduced by all doses, and this change was most marked after 1000 mg (from 10.9 +/- 1.4 to 5.6 +/- 0.5 mol%, P < 0.01). Biliary cholesterol saturation improved significantly only after 750 and 1000 mg daily.

Adolescent↗