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Biomedical subjects

D Ryder

Publications and source records attributed to D Ryder.

12 recordsLinked to original sources
PubMed1992

The disposition of dapsone in cirrhosis.

Acetylation and N-hydroxylation of dapsone were evaluated in drug-free, non-smoking, normal subjects and subjects with cirrhosis (n = 7 for each group) after oral administration of 100 mg dapsone. Acetylation was not correlated with oral dapsone clearance or reduced in cirrhosis (0.37 +/- 0.43 versus 0.52 +/- 0.32). Fractional metabolic clearance of dapsone to its hydroxylamine was associated with dapsone oral clearance (r = 0.96, p less than 0.001, n = 14). In patients with cirrhosis, liver disease was associated with a trend to reduction in oral clearance (22%) and metabolic clearance of dapsone (48%). Protein binding was minimally reduced by cirrhosis (73% +/- 1% versus 69% +/- 3% in patients with cirrhosis (p less than 0.02). The dapsone recovery ratio was validated as a phenotypic index of the metabolic clearance of dapsone (r = 0.74, p less than 0.05). In an extended comparison of 14 patients with cirrhosis to 70 control subjects, cirrhosis was associated with reductions of 28% in dapsone recovery ratio (p less than 0.001), and 37% in acetylation ratio (p less than 0.01). Neither dapsone recovery ratio nor acetylation ratio correlated with Pugh Score, conventional liver function tests, indocyanine green clearance, or phenotypic measures of S-mephenytoin hydroxylase or debrisoquin hydroxylase activity. We conclude that cirrhosis is associated with minor changes in dapsone disposition and that dosage modification is not required. In addition, there is evidence that cirrhosis has a selective influence on activity of individual isozymes of cytochrome P450.

Acetylation↗
PubMed1991

A pharmacodynamic interaction between caffeine and phenylpropanolamine.

The pharmacokinetic and pharmacodynamic interaction between caffeine and phenylpropanolamine has been investigated in six normal subjects in a double-blind, placebo-controlled, Latin-square design study. After 3 days on a 100 mEq sodium, xanthine-free diet, fasting subjects were placed in a supine position and were given 25 mg phenylpropanolamine and placebo, 250 mg caffeine and placebo, or 25 mg phenylpropanolamine and 250 mg caffeine in random order. Blood pressure, pulse, plasma renin activity, and plasma catecholamine levels were measured before and for 3 hours after drug administration. Plasma and urinary phenylpropanolamine, caffeine, and caffeine metabolite levels were measured serially for 48 hours. Coadministration of caffeine and phenylpropanolamine produced an additive increase in blood pressure. This effect could not be explained by any pharmacokinetic interaction between the two drugs and occurred even though phenylpropanolamine attenuated the epinephrine and renin response to caffeine. These data suggest that a clinically relevant interaction between caffeine and phenylpropanolamine does occur in drug-free subjects and that this interaction cannot be explained by a mechanism involving the sympathetic or renin-angiotensin systems.

Adult↗
PubMed1991

Post consolidation therapy for adult patients with acute myeloid leukaemia.

One hundred and sixteen adult patients aged 14-73 with previously untreated acute myeloid leukaemia received induction and consolidation chemotherapy with daunorubicin, cytosine arabinoside and thioguanine. Two novel approaches to post consolidation therapy have been investigated. Patients aged 50 years or less who had no suitable matched allogeneic donor were considered for autologous bone marrow transplantation (BMT) using bone marrow which had been cultured in vitro for 14 d. Patients over the age of 50 years with normal bone marrow cellularity and peripheral blood count were treated with a single oral dose of busulphan 100 mg/m2 (without BMT rescue) 3 months following the completion of consolidation therapy. Eighty-seven patients (75%) achieved a complete remission. Of 70 patients who completed consolidation therapy, 40 were aged less than or equal to 50 years and 30 were greater than 50 years. Forty-three patients went on to receive post consolidation therapy in first CR (autologous BMT 12, allogeneic BMT 7, busulphan therapy 24). The event-free survival at 4 years was 47% for autologous BMT, 34% for allogeneic BMT and 45% for busulphan-treated patients. The survival for the older cohort of patients who received post consolidation therapy with single dose busulphan therapy was encouraging, and this agent should be considered for future post consolidation strategies.

Acute Disease↗
PubMed1991

Caffeine potentiates the renin response to diazoxide in man. Evidence for a regulatory role of endogenous adenosine.

In the rat and dog, exogenous adenosine inhibits renin release and adenosine receptor blockade augments stimulated renin release, suggesting that endogenous adenosine contributes to the regulation of renin release. The present study examines the role of endogenous adenosine in the regulation of renin in humans. The ability of the adenosine receptor blocker, caffeine, to augment renin release in response to the vasodilator, diazoxide, has been investigated in eight normal subjects in a double-blind, placebo-controlled, cross-over study. During each arm of the study, subjects on a 150 mEq of sodium, xanthine-free diet received caffeine (250 mg 3 times daily) or placebo for 3 days before and on the study day, when they were given an i.v. loading dose of diazoxide (4 mg/kg) followed by a 3-hr continuous infusion (0.67 mg/kg/hour). PRA, caffeine and diazoxide levels were measured before, during and after the diazoxide infusion. PRA measurements were repeated with subjects standing, 6 hr after starting diazoxide. Administration of diazoxide resulted in a modest tachycardia and a small, but significant, decrease in BP. Supine PRA was elevated during and after the diazoxide infusion and rose further with standing. Although there was no difference in plasma diazoxide levels, maximal pulse or BP response to diazoxide between the two arms of the study, the renin response was significantly greater in the presence of caffeine. These data confirm that caffeine augments the PRA response to diazoxide and suggest that endogenous adenosine inhibits stimulated renin response in humans.

Adenosine↗
PubMed1988

Alcohol-related problems in a general hospital and a general practice: screening and the preventive paradox.

A screening questionnaire was used to identify persons with alcohol-related problems in a general hospital and in a general practice. The questionnaire consisted of 16 questions about alcohol-related problems during the past 12 months, and two questions which assessed the quantity and frequency of usual alcohol consumption. The questions about alcohol-related problems led to the identification of more persons with problems than did the consumption questions alone. If the consumption questions only had been used to identify a high-risk group of consumers, and if all these subjects had been persuaded to reduce their alcohol consumption to a low-risk level, the reduction in the number of persons who experienced alcohol-related problems would have been modest. This is compatible with the phenomenon of the preventive paradox, and it is concluded that any screening questionnaire must include questions other than those about high-risk levels of consumption if it is to identify the majority of at-risk persons.

Adolescent↗
PubMed1987

Extended esophageal myotomy and short total fundoplication hernia repair in diffuse esophageal spasm: five-year review in 34 patients.

Diffuse esophageal spasm (DES) is a rare disease, and its surgical management is controversial. There are seven major reported series totaling 148 patients and six operative variations depending on the extent of myotomy and whether or not a hernia repair should be added. There are no five-year follow-up reports. In the present study of 34 patients followed for at least five years, all had a myotomy from the apex of the chest through the high-pressure zone and all had a total fundoplication hernia repair, 16 with gastroplasty and 16 with a standard Nissen fundoplication. The length of the completion fundoplication is reduced to less than 0.5 cm to avoid problems of overcompetence. There were no operative deaths. Follow-up is 100% by clinical history, 82.4% by radiology, and 61.8% by manometry. Radiological follow-up showed no recurrence or reflux, although 1 patient had esophageal mucus retention. Thirty patients (88.2%) are eating normally without dysphagia or spontaneous pain. Two patients (5.9%) have mild dysphagia, and 1 of them also has mild spontaneous pain. One patient has major residual dysphagia, which is being treated conservatively, and 1 has required colon interposition. Good-quality results have been achieved in 94% of patients now followed 5 to 10.7 years.

Esophageal Diseases↗
PubMed1979

Radiologic investigation of splenic trauma.

The radiologic findings in blunt and penetrating splenic injuries are discussed with emphasis on the angiographic demonstration of these injuries. The angiographic findings are correlated with the time interval between trauma and radiologic investigation.

Angiography↗