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Biomedical subjects

S M Murphy

Publications and source records attributed to S M Murphy.

At least 73 records · Page 4Linked to original sources

A double-blind comparison of the effects of gradual withdrawal of lorazepam, diazepam and bromazepam in benzodiazepine dependence.

Using a double-blind procedure, 68 patients with putative benzodiazepine dependence were randomly allocated to one of three groups given lorazepam (n = 22), diazepam (n = 23) or bromazepam (n = 23) in doses equivalent to those of the patients' original benzodiazepine. After four weeks the dosage was reduced in 25% quantities until no further benzodiazepines were taken. A total of 23 patients dropped out during the study, ten on lorazepam (one of whom committed suicide), seven on diazepam and six on bromazepam. There were few differences in withdrawal symptoms between the three groups but, despite the higher dropout rate, these symptoms were somewhat less marked in the lorazepam group. Withdrawal symptoms were greater in patients who had taken a benzodiazepine for greater than 5 years and were most marked in those with personality disorders, predominantly dependent ones.

Adult↗

Effects of ethanol on amino acid transport in basolateral liver plasma membrane vesicles.

Ethanol has been reported to inhibit hepatocellular processes such as gluconeogenesis and protein synthesis that depend, in part, on amino acid uptake. Since previous studies in cultured hepatocytes indicate that ethanol may have a direct and selective inhibitory effect on amino acid transport, the effects of ethanol on amino acid uptake into basolateral (sinusoidal) rat liver plasma membrane (blLPM) vesicles were examined. Uptake of [3H]alanine, [3H]leucine, and [35S]cysteine was measured by a rapid Millipore filtration technique in the presence of inwardly directed Na+ and K+ gradients and under tetramethylammonium (TMA+)- and Na+-equilibrated conditions. Ethanol preincubation produced a concentration-dependent inhibition of Na+-dependent alanine and cysteine uptake; no effect was observed on either Na+-independent alanine and cysteine uptake or Na+-independent leucine transport. Ethanol had no effect on L-alanine transport under Na+-equilibrated conditions; however, initial rates of 22Na flux were enhanced in the presence of ethanol. On the basis of differences in 2-(methylamino)isobutyrate and L-cysteine sensitivity, ethanol inhibition of Na+-dependent alanine transport in blLPM vesicles largely but not exclusively corresponded to the hormone-responsive system A for amino acid transport described in isolated hepatocytes. Kinetic analysis showed that ethanol treatment resulted in an alteration in the apparent maximum velocity of reaction (Vmax) of Na+-dependent alanine transport without affecting the apparent Km for alanine. The inhibitory effects of ethanol on the time course of Na+-dependent alanine uptake were reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

Comparative assessment of efficacy and withdrawal symptoms after 6 and 12 weeks' treatment with diazepam or buspirone.

Fifty-one out-patients presenting with generalised anxiety disorder were included in a double-blind trial, and treated with either buspirone (a new non-benzodiazepine antianxiety drug) or diazepam over 6 or 12 weeks, after which they were abruptly withdrawn and continued on placebo to 14 weeks. Ratings of anxiety and other symptoms were administered fortnightly and additional withdrawal symptoms noted. Forty patients completed the study; 8 of the 11 drop-outs were taking buspirone. Both drugs reduced anxiety, diazepam more rapidly, but with greater withdrawal symptoms, particularly after 6 weeks. Regular treatment with diazepam for 6 weeks leads to a significant risk of pharmacological dependence that is not present with buspirone.

Adolescent↗

Na+-glycine cotransport in canalicular liver plasma membrane vesicles.

By use of purified rat canalicular liver plasma membrane (cLPM) vesicles, the present study determined the driving forces for glycine transport across this membrane domain. Initial rates of [3H]glycine uptake (10 microM) in cLPM vesicles were stimulated by an inwardly directed Na+ gradient but not by a K+ gradient. Na+ gradient-dependent uptake of glycine demonstrated cation specificity for Na+, dependence on extravesicular Cl-, stimulation by an intravesicular-negative membrane potential, and inhibition by dissipation of the Na+ gradient with gramicidin D. Na+ gradient-dependent glycine cotransport also demonstrated greater sensitivity to inhibition by sarcosine than 2-(methylamino)-isobutyric acid. Accelerated exchange diffusion of [3H]glycine was demonstrated in the presence of Na+ when cLPM vesicles were preloaded with glycine but not with L-alanine or L-proline. Substrate velocity analysis of net Na+-dependent [3H]glycine uptake over the range of amino acid concentrations from 5 microM to 5 mM demonstrated two saturable transport systems, one of high capacity (2.2 +/- 0.2 nmol.mg protein-1.15 s-1) and low affinity (11.2 +/- 1.7 mM) and one of low capacity (51 +/- 14 pmol.mg protein.15 s-1) and comparatively high affinity (66 +/- 12 microM). These results indicate that, in addition to previously described neutral and anionic amino acid transport systems, Na+ gradient-dependent glycine transport mechanisms are present on the canalicular domain of the liver plasma membrane. These canalicular reabsorptive mechanisms may serve to reclaim some of the glycine generated within the canalicular lumen from the intrabiliary hydrolysis of glutathione.

Amino Acid Transport Systems, Neutral↗

Study of the possible enteropancreatic circulation of pancreatic amylase in the dog.

The possible existence of an enteropancreatic circulation of amylase was investigated in the dog. Endogenous amylase concentration in pancreatic venous blood was consistently greater than that in arterial blood, indicating a net flux of amylase from the pancreas to blood. Less than 0.02% of the metabolic clearance of 125I-amylase was accounted for by 125I-amylase in pancreatic secretions, indicating a minimal flux of amylase from the blood to pancreatic secretions. The venous-arterial amylase concentration across gut segments containing large quantities of amylase was not significantly different from 1.00, indicating absorption of less than 0.2% of the luminal amylase per hour. No 125I-amylase was detectable in serum after endoscopic instillation of labeled enzyme into the duodenum. These studies demonstrate negligible intestinal absorption of amylase and negligible pancreatic extraction of amylase, indicating negligible enteropancreatic circulation of pancreatic amylase in the dog.

Amylases↗

Gonorrhoea: signs, symptoms and serogroups.

Over 19 weeks, 104 male patients attending a genitourinary medicine clinic with gonococcal urethritis were asked to complete a questionnaire detailing symptoms. Sixty-seven questionnaires were duly completed. The examining nurse documented signs. Ninety-one isolates of Neisseria gonorrhoeae were serogrouped and auxotyped, 55 of these were from patients who had completed a questionnaire. Patients presented earlier if they had a past history of gonorrhoea (p = 0.02). The serogroup of N. gonorrhoeae did not influence the amount of discharge, the presence of meatal inflammation, dysuria or penile tip irritation or the delay in presentation after appearance of discharge. Auxotype AHU was not associated with asymptomatic gonorrhoea.

Gonorrhea↗