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Biomedical subjects

D Stevenson

Publications and source records attributed to D Stevenson.

At least 91 records · Page 5Linked to original sources
PubMed1986

A bioavailability study of two preparations of tamoxifen after single doses.

The bioavailability of two different tablet formulations of tamoxifen was studied in twelve healthy male volunteers. Two tablets, each of 10 mg, of both preparations were administered orally at intervals of two weeks in a randomized cross-over design. Samples of blood for tamoxifen measurement were taken for up to 48 h following administration. Tamoxifen was measured by an HPLC method sensitive to 2.0 ng ml(-1). The area under the concentration-time curve was similar for both preparations. The study, therefore, did not demonstrate any differences between the bioavailability of the two preparations of tamoxifen.

Journal Article↗
PubMed1986

Validity of skinfold thickness measures of formerly obese adults.

UNLABELLED: To assess the validity of skinfold thickness estimates of body fatness in formerly morbid obese adults, 23 patients (17 women, 6 men) who had completed a protein-sparing modified fast were studied. Mean +/- SD weight loss was 60.7 +/- 20.6 kg for men and 42.6 +/- 11.5 kg for women. Body density and percent body fatness were determined after weight loss according to four commonly used skinfold equations: Pollock (P); Durnin-Rahaman (D-R); Durnin-Womersley (D-W); and, Jackson-Pollock (J-P). The validity of these measurements was assessed by hydrostatic weighing, which revealed a percent body fatness of 20.4 +/- 6.5 for men and 29.8 +/- 8.4 for women. The mean difference and total error (square root of the mean of squared deviations) between skinfold predicted and hydrostatically-determined percent body fatness for each skinfold equation were: P, 2.0 and 4.9; D-R, 4.2 and 6.6; D-W, 7.1 and 8.4; and, J-P, 0.7 and 4.4. With the exception of the latter equation, all significantly overestimated (p less than 0.01) hydrostatically-determined percent body fatness. CONCLUSION: Select skinfold equations may result in a marked overestimation of body fatness in formerly obese patients.

Adipose Tissue↗
PubMed1986

The bioavailability of Tamoplex (tamoxifen). Part 1. A pilot study.

Tamoxifen and N-desmethyltamoxifen plasma concentrations were found to be similar after a first single dose and during two months therapy with Tamoplex or Nolvadex in groups of 6 and 8 patients, respectively. Single dose absorption results in 10 healthy male volunteers demonstrated bioequivalence of Tamoplex and Nolvadex 10 mg tablets. A large interindividual variation in tamoxifen absorption data was observed, probably related to the dominating metabolic clearance of tamoxifen.

Adult↗
PubMed1985

Effects of valproate on hyponeophagia in rats: competitive antagonism with picrotoxin and non-competitive antagonism with RO 15-1788.

The effects of valproate (30-500 mg/kg), alone and in combination with picrotoxin (1.5 mg/kg) or RO 15-1788 (10 mg/kg) were studied in two experiments on hyponeophagia in rats. Valproate reduced eating latency and increased eating time and amount eaten of novel food, except at 500 mg/kg which reduced feeding. Picrotoxin induced generally opposite actions alone and shifted valproate dose/response curves to the right. RO 15-1788 had no detectable intrinsic action, but prevented both the behavioural facilitation and inhibition produced by valproate. These findings are discussed in the context of the GABA hypothesis of benzodiazepine action, with the conclusions that they provide behavioural support for the hypothesis of a receptor complex with GABA and benzodiazepine binding sites, and that an optimal and submaximal level of activity at the benzodiazepine site is a necessary condition for anxiolytic actions of valproate.

Animals↗
PubMed1985

The natural history of subependymal germinal matrix hemorrhage.

A prospective study of 377 premature infants (less than or equal to 1500 gm) was undertaken to delineate the natural history of subependymal/intraventricular hemorrhage (S/IVH) and its complications using ultrasound (US) and computed tomography (CT). Low grade (I, II) S/IVH had a low mortality while higher grades (III, IV) still had elevated mortality rates. The addition of intraparenchymal hemorrhage (IPH) to S/IVH incrementally increased the incidence of death and other complications, suggesting IPH hemorrhage should be categorized separately. When a specific day could be identified, S/IVH had its onset in the first 7 days of life with peak incidence occurring on day 3. S/IVH appeared to be an event limited to less than 24 hours in all but 5% of infants in whom progression of hemorrhage was documented over a 24-hour period. The mortality rate of these progressive hemorrhages was high, 50%. The benign phenomenon of late S/IVH was detected in 5% of infants. These hemorrhages were clinically silent and of minor severity. Several complications of S/IVH were detected. Hydrocephalus was a significant complication only for higher grades of S/IVH. When present, severe hydrocephalus had an early onset and reached a maximum at around 3 weeks of age. "Atrophic change" of a cerebral hemisphere was detected in 30% of all S/IVH infants, while this was not seen in nonS/IVH infants. This "atrophic" abnormality had a marked predilection for the left hemisphere, independent of the site of the S/IVH. Periventricular leukomalacia (PVL) was documented by US in 2% of infants and could be detected in the first week of life. PVL presented in the first week of life as an echogenic lesion which developed "cystic" changes at approximately 3-4 weeks of age. This complication should be categorized separately from S/IVH.

Atrophy↗
PubMed1985

Effects of short-term, high-dose prednisone treatment of patients with HBsAg-positive chronic active hepatitis.

We conducted a clinical trial to study the effects of a 10-week course of prednisone therapy and its withdrawal on serum aminotransferase levels and on hepatitis B virus (HBV) markers in patients with hepatitis B surface antigen (HBsAg) positive chronic active hepatitis (CAH-B). Eighteen patients with CAH-B were treated with prednisone, while another 18 patients matched for age, sex, race and sexual preference were followed simultaneously without treatment for the same duration. Nine of 18 prednisone-treated patients became transiently DNA polymerase positive. All nine patients developed a transient rise in serum alanine aminotransferase (ALT) levels of greater than 300 U/L above baseline values, which was associated with a drop in HBsAg levels from a mean of 186 micrograms/ml prior to therapy to 92 micrograms/ml at 6 months following treatment. Six of these patients developed fatigue, anorexia and dark urine, and four also developed either ascites or hemorrhage from esophageal varices, which was accompanied by hepatic encephalopathy. All six of these patients had histologic evidence of CAH with cirrhosis. In comparison, none of the control, untreated patients with CAH-B had any change in either HBV markers or serum ALT levels. Therefore, even a short course of prednisone in patients with CAH-B with cirrhosis is detrimental and its use should be discouraged.

Adult↗
PubMed1985

Production of (S)-3-chlorolactaldehyde from (S)-alpha-chlorohydrin by boar spermatozoa and the inhibition of glyceraldehyde 3-phosphate dehydrogenase in vitro.

The (S)-isomer of the male antifertility agent alpha-chlorohydrin was metabolized by mature boar spermatozoa in vitro to (S)-3-chlorolactaldehyde. This oxidative process, which did not occur when (R)-alpha-chlorohydrin was offered as a substrate, was catalysed by an NADP+-dependent dehydrogenase that converts glycerol to glyceraldehyde. (S)-3-chlorolactaldehyde, produced by this metabolic reaction or when added to suspensions of boar spermatozoa, was a specific inhibitor of glyceraldehyde 3-phosphate dehydrogenase as assessed by the accumulation of fructose 1,6-bisphosphate and the triosephosphates. When glycerol and (S)-alpha-chlorohydrin were added concomitantly to boar spermatozoa in vitro, the presence of glycerol decreased the degree of inhibition of glyceraldehyde 3-phosphate dehydrogenase. Extracts of glyceraldehyde 3-phosphate dehydrogenase that were obtained from boar spermatozoa incubated with (S)-alpha-chlorohydrin or (R,S)-3-chlorolactaldehyde showed significant reductions in their enzymic activity.

Aldehydes↗
PubMed1984

The action of (R)- and (S)-alpha-chlorohydrin and their metabolites on the metabolism of boar sperm.

The action of (R,S)-alpha-chlorohydrin in inhibiting glycolysis in boar sperm is due to the (S)-isomer. Its effect on the concentrations of glycolytic intermediates suggests that the pathway is inhibited at the glyceraldehyde 3-phosphate dehydrogenase reaction. alpha-Chlorohydrin is oxidized by boar liver homogenates via 3-chlorolactaldehyde to 3-chlorolactate. Racemic mixtures of both compounds, and a proposed metabolite, 3-chloropyruvate, inhibit the oxidative metabolism of fructose, lactate and pyruvate possibly by interfering with processes occurring within the sperm mitochondria. It is proposed that the toxic action of these metabolites account for the effects of (R)-alpha-chlorohydrin on sperm motility, as this compound possesses no antifertility activity of itself.

Animals↗
PubMed1983

Formation of the active antifertility metabolite of (S)-alpha-chlorohydrin in boar sperm.

The male antifertility agent (S)-alpha-chlorohydrin (I) is metabolized by boar sperm to (S)-3-chlorolactaldehyde (II) by an enzyme that is involved in the oxidation of glycerol to glyceraldehyde. The presence of glycerol decreases the activity of this enzyme towards (S)-alpha-chlorohydrin in vitro thereby preventing the formation of (S)-3-chlorolactaldehyde, an inhibitor of glyceraldehyde 3-phosphate dehydrogenase in boar sperm.

Animals↗
PubMed1983

Natural killer cell activity during mouse hepatitis virus infection: response in the absence of interferon.

The ability of the JHM3 strain of mouse hepatitis virus (MHV) to induce natural killer (NK) cells was examined. Infection of C57BL/6 (B6) mice with this virus resulted in the augmentation of natural cytotoxicity against YAC-I target cells in the absence of a detectable interferon response. The cells responsible for this increased cytotoxicity were sensitive to complement-mediated lysis with an anti-Q-5 reagent but not with a Thy 1.2 antiserum, indicating that they possess an NK-like surface phenotype. Although variation in the NK response of individual B6 mice following JHM virus infection was found, even the animal with the most responsive NK cell population had no detectable interferon in the spleen. This finding contrasted with observations with an unrelated virus (lymphocytic choriomeningitis virus) and a serologically related strain of MHV. Infection with both of these viruses induced augmented NK cell activity and interferon responses. In addition, we found that neither the ability to mount an augmented NK cell response nor preferential lysis of virus-infected targets correlated with resistance or susceptibility to JHM virus infection.

Animals↗
PubMed1983

Studies on the metabolism of the new anti-hypertensive agent, indoramin, in man.

The absorption, metabolism and excretion of the new antihypertensive agent indoramin (Baratol) have been studied in male volunteers following oral administration of the drug labelled either with 14C or with tritium. Absorption of the drug proceeded at moderate rate, peak plasma radioactivity levels being seen by 3 h after dosing. Metabolism was extensive as shown by very little unchanged compound appearing in urine. Two major urinary metabolites accounting for some 35-40% of the renally excreted material were identified as acid labile conjugates of indoramin itself and indole 6-hydroxylated indoramin. The pattern of biotransformation appeared to be similar to that in the patas monkey, the species used in the long term safety evaluation of the drug. Excretion of the drug and metabolites occurred primarily via the faeces which accounted for 49.7 +/- 4.9% of the dose. A further 31.7 +/- 2.4% was recovered in the urine. Renal elimination of total radioactivity occurred in an apparently monoexponential manner with a half-life of 11.9 +/- 1.2 h.

Adult↗
PubMed1983

Mouse interferon receptors: a difference in their response to alpha and beta interferons.

The interferon receptors of C3H/10T1/2 mouse cells respond differently to alpha and beta interferons under certain conditions. If C3H/10T1/2 cells which have been maintained in logarithmic growth phase are exposed to trypsin or Pronase immediately before they are treated with mouse interferons, they evince an antiviral response to alpha interferon but not to beta interferon. In contrast, contact-inhibited C3H/10T1/2 cells, L-929 mouse cells or human HEL cells lost the ability to respond to both alpha and beta interferons after treatment with trypsin or Pronase. When L-929 cells are incubated at 37 degrees C following exposure to these proteolytic enzymes, they completely regain their ability to respond to mouse beta interferon within 2 h. These observations suggest that the receptors for alpha and beta interferons are different in their topographical distribution in C3H/10T1/2 cells.

Animals↗
PubMed1982

Inhibition of fructolysis in boar spermatozoa by the male antifertility agent (S)-alpha-chlorohydrin.

The (S)-isomer of the male antifertility agent alpha-chlorohydrin strongly inhibited the oxidative metabolism of fructose by boar spermatozoa in vitro. The result of this action, which has been deduced to be an inhibition of glyceraldehydephosphate dehydrogenase, caused an accumulation of fructose-1,6-bisphosphate and the triosephosphates, and a decrease in substrate-level phosphorylation with a concomitant lowering of the energy charge potential of the spermatozoa. The (R)-isomer of alpha-chlorohydrin had no inhibitory activity on fructolysis. A study of the comparative metabolism of (R)-[3-36Cl]-alpha-chlorohydrin and (R,S)-[3-36Cl]-alpha-chlorohydrin by boar spermatozoa showed that it is the (S)-isomer that specifically undergoes a process of oxidative metabolism to (R)-3-chlorolactaldehyde. It is proposed that this endogenous oxidation product, which has the same absolute configuration as the substrate for glyceraldehyde-phosphate dehydrogenase, is the active metabolite of (S)-alpha-chlorohydrin that inhibits this enzyme. Exogenous (R,S)-3-chlorolactaldehyde inhibited the oxidative metabolism of fructose by boar spermatozoa, apparently by a mechanism similar to that of (S)-alpha-chlorohydrin.

Adenine Nucleotides↗