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Biomedical subjects

C Manning

Publications and source records attributed to C Manning.

14 recordsLinked to original sources
PubMed1992

Central nervous system effects of meclizine and dimenhydrinate: evidence of acute tolerance to antihistamines.

Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate, 100 mg, at 8:00 AM, 12:00 PM, and 4:00 PM; meclizine, 50 mg, at 8:00 AM, with placebo at 12:00 PM and 4:00 PM; or placebo at all three times in this randomized, double-blind, three-way crossover study. Impairment of mental performance was assessed by choice reaction time testing and digit symbol substitution scores. Drowsiness was self-assessed on the Stanford Sleepiness Scale and on a visual analog scale. Both antihistamines produced changes in digit symbol substitution, recognition time, and subjective assessments of sleepiness different from placebo. Expressed as change from baseline, the greatest reductions in digit symbol substitution scores after dimenhydrinate occurred 3 hours after the first dose (6.6 +/- 7) and were not different from the greatest measured change after meclizine (5.8 +/- 8), which occurred 9 hours after the dose was administered. Similar results were obtained with the other psychometric test scores. Self-rated sleepiness after dimenhydrinate was greatest 1 hour after the first dose, and was significantly greater than the largest degree of sleepiness after meclizine, which occurred at 7 hours after the dose. The effects of the first dose of dimenhydrinate on psychometric test scores were compared with the magnitude of the effects produced by subsequent doses. The magnitude of effect of the first dose of dimenhydrinate was significantly greater than the magnitude of effect produced by subsequent doses. The data suggest the possibility that acute tolerance to central nervous system impairment develops with multiple doses of dimenhydrinate.

Adolescent↗
PubMed1992

Pharmacokinetics and metabolism of racemic 2',3'-dideoxy-5-fluoro-3'-thiacytidine in rhesus monkeys.

2',3'-Dideoxy-5-fluoro-3'-thiacytidine (FTC) is a nucleoside analog that selectively inhibits human immunodeficiency and hepatitis B viruses in vitro. In this study, the preclinical pharmacokinetics of racemic FTC in rhesus monkeys following intravenous and oral administration were characterized. The terminal half-life of FTC was independent of the route of administration and averaged 1.34 +/- 0.18 h (mean +/- standard deviation). Total clearance of FTC was moderate to high, averaging 1.49 +/- 0.24 liters/h/kg. Qualitative assessment of urine samples suggests that renal excretion of unchanged FTC was the major route of elimination of the nucleoside. The compound was also eliminated by metabolism and the deaminated biotransformation product 2,3'-dideoxy-5-fluoro-3'-thiauridine (FTU) was detected in serum and urine. This metabolite has no antiviral activity in human lymphocytes and liver cells. FTC and the metabolite FTU were conjugated, to a minor extent yielding the corresponding glucuronides. No 5-fluorouracil was detected in serum or urine. This is consistent with chromatographic studies using a chiral column that indicated that when racemic FTC is treated with cellular cytidine-deoxycytidine deaminase, the D-(+)-enantiomer of FTC is slowly deaminated to D-(+)-FTU, whereas the L-(-)-enantiomer is essentially resistant to this enzyme. The steady-state volume of distribution of FTC in serum averaged 2.23 +/- 0.42 liters/kg, and the nucleoside analog was distributed into the cerebrospinal fluid, which suggests that this drug penetrated the blood-brain barrier. Absorption of FTC after oral administration was rapid, with bioavailability averaging 73 +/- 6%. Taken together, the results indicate that the unusual L-(-)-enantiomer of FTC should be evaluated further in rhesus monkeys prior to determination of whether this compound is useful for treatment of human immunodeficiency and hepatitis B virus infections.

Administration, Oral↗
PubMed1990

The pharmacodynamics of ethanol: effects on performance and judgment.

The objective and subjective effects produced by increasing and decreasing ethanol concentrations were studied in healthy volunteers on three separate occasions. A randomized, double-blind, placebo-controlled, four-way crossover study was used to determine whether there is any disparity between the time course of blood ethanol concentration and its effects on either objective test performance or self rated impairment. On each study day the subjects received one of four treatments consisting of either placebo or sufficient alcohol to achieve peak estimated blood alcohol concentration (Est.BAC) of 0.07 gm/dL, 0.1 gm/dL or 0.14 gm/dL. Est.BAC determined from breath alcohol concentrations were measured 20 minutes after each "dose" until peak Est.BAC was achieved, then 1, 2, 3.5, and 4.5 hours after peak Est.BAC. Digit symbol substitution (DSS), simulated driving reaction time (SDRT), choice reaction time (CRT) and self assessment of impairment (SRI) were measured simultaneously with Est.BAC. Changes in objective performance test scores were well correlated with Est.BAC (r2 = 0.60 P less than .01). Maximum impairment in test performance occurred at the same time as peak Est.BAC. Threshold Est.BAC needed to produce changes in objective test scores greater than placebo were 0.06 +/- 0.01 for DSS, 0.04 +/- 0.01 for SDRT, and 0.04 +/- 0.02 for CRT. There was no evidence of between dose or within dose tolerance to the effects produced by various Est.BAC on any of these performance tests. Subjects' self rated degrees of impairment at various Est.BAC were influenced by whether alcohol concentrations were rising or falling. Subjective impairment ratings were greater while alcohol concentrations were increasing compared to the same Est.BAC occurring during falling alcohol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A review of the effects of antihistamines on mental processes related to automobile driving.

The newer, second-generation H1-receptor antagonists have been shown to have potent antiallergic effects without inducing sleepiness. However, because traditional antihistamines may cause functional or cognitive impairment, the clinician still must consider warning patients about activities that could be hazardous. Because the effects of drugs on driving an automobile are difficult to measure directly, studies must use surrogate activities in a laboratory setting. Effects of antihistamines on the central nervous system are assessed with psychomotor tests, which are selected on the basis of their relativity to real-world activities, to develop a profile of mental processes that may be affected. This article reviews the psychomotor tests and study design used to characterize the intensity and duration of drug effects after single and multiple doses and in combination with other impairing agents such as ethanol. Several studies have been published that assess the effects of cetirizine, an H1-receptor blocker, on mental performance. In the study discussed here, diphenhydramine hydrochloride and hydroxyzine were used as positive controls to demonstrate that the period during which some traditional antihistamines impair performance is different than the period of reported drowsiness they induce. The results of this series of studies show that cetirizine induced minimal changes in mental performance tests and only following the highest (20 mg) dose studied.

Automobile Driving↗
PubMed1989

Jejunal atresia with 'apple peel' deformity. A report of eight survivors.

Jejunal atresia with an "apple peel" deformity is one of the most severe forms of intestinal atresia. Until quite recently, neonatal mortality rates as a result of this anomaly were high. Early diagnosis, appropriate surgery, and prolonged parenteral nutrition have led to a spectacular improvement of the survival rates. We are reporting eight cases of apple peel atresia--all eight patients survived. The pathophysiology, diagnostic aspects, surgical approaches, and postoperative management are discussed.

Female↗
PubMed1978

In vivo effect of colchicine on hepatic protein synthesis and on the conversion of proalbumin to serum albumin.

Treatment of rats with 0.5-25 mumol/100 g body weight of colchicine for 1 h or more caused an inhibition of hepatic protein synthesis. This effect was not seen if animals were exposed to colchicine for less than 1 h. The delayed inhibition of protein synthesis affected both secretory and nonsecretory proteins. Treatment with colchicine (15 mumol/100 g) for 1 h or more caused the RNA content of membrane-bound polysomes to fall but did not change the polysomal profile of this fraction. By contrast, the total RNA content in the free polysome cell fraction was increased, and this was due to the presence of more ribosomal monomers and dimers. Electron microscope examination of the livers from rats treated for 3 h with colchicine showed an accumulation of secretory vesicles within the hepatocytes and a general distention of the endoplasmic reticulum. Administration of radioactive L-leucine to the rats led to an incorporation of radioactivity into two forms of intracellular albumin which were precipitable with antiserum to rat serum albumin but which were separable by diethylaminoethyl-cellulose chromatography. One form has arginine at the amino-terminal position and is proalbumin, and the other form, which more closely resembles serum albumin chromatographically, has glutamic acid at its amino terminus. Only proalbumin was found in rough and smooth endoplasmic reticulum fractions and in a Golgi cell fraction wich corresponds morphologically to mostly empty and partially filled secretory vesicles. However, in other Golgi cell fractions which were filled with secretory products, both radioactive proalbumin and serum albumin were found. This indicates that proalbumin is converted to serum albumin in these secretory vesicles just before exocytosis. Colchicine delayed the discharge of radioactive albumin from these filled secretory vesicles and caused an accumulation of both proalbumin and serum albumin within these cell fractions.

Animals↗
PubMed1978

Leg lengthening.

Two hundred eleven leg lengthening operations have been carried out at the Royal National Orthopaedic Hospital, London, in 192 patients between 1966 and 1977. The results were analyzed in the 143 patients who had reached skeletal maturity. A 5 cm gain in length using Anderson's modification of Abbott's lengthening machine was achieved in 21 femora and 122 tibiae. There was no significant difference in the sexes, 98 boys and 94 girls. Average difference in leg length before operation was 5.75 cm (11.7--3.0 cm). Average reduction in difference 3.06 cm (7.5--4.5 cm). Average difference at maturity 2.48 cm (9.5--0.5 cm). Fractures occurred in 30 patients all of which united, but some lost part of the length gained. Most serious was a decision to amputate in 2 patients due to severe discrepancy in one patient and foot deformity in another. There were no failures of union, no long-term sepsis and no deaths.

Amputation, Surgical↗
PubMed1973

Epiphysiodesis.

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Epiphyses, Slipped↗