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Biomedical subjects

S Vickers

Publications and source records attributed to S Vickers.

At least 37 records · Page 2Linked to original sources
PubMed1991

Single-dose pharmacokinetics of 14C-lovastatin in chronic renal failure.

An open study on the pharmacokinetics of lovastatin was conducted in six patients with chronic renal failure (mean creatinine clearance, 0.40 ml/sec; range, 0.20 to 0.65 ml/sec) and seven healthy subjects. Plasma levels of 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitory activity (total and active) and total radioactivity were determined over 168 hours after a single dose of 80 mg 14C-lovastatin. The mean area under the plasma concentration-time curve for active inhibitors were 606 +/- 346 and 282 +/- 138 ngEq.hr/ml (p = 0.04) in patients and control subjects, respectively. Total inhibitors in plasma and total radioactivity were similarly elevated in patients with chronic renal failure. Results indicate that patients with severe renal dysfunction have altered elimination kinetics of lovastatin. Current ongoing clinical studies in patients with renal dysfunction will allow better assessment of the pharmacodynamic meaning of our observations.

Adult↗
PubMed1990

Molecular biology of circulatory shock. Part II. Expression of four groups of hepatic genes is enhanced after resuscitation from cardiogenic shock.

Despite an initially successful resuscitation from circulatory shock, multiple organ failure (MOF) develops in some patients. The marked biochemical alterations associated with shock and MOF include clinically important changes in gene expression, such as altered rates of albumin and procoagulant synthesis. To characterize the MOF-associated changes at the cellular level, sequential liver biopsies were obtained from a swine model of cardiogenic shock associated with MOF. Preshock and postresuscitation biopsies were used not only to create a complementary DNA (cDNA) library but also to screen, to confirm, and, in nine out of 12 cases, to specifically identify genes whose expression is enhanced at least fivefold after resuscitation. The twelve genes thus characterized can be separated according to function into distinct groups, including the acute-phase genes and the heat-shock genes. Expression of acute-phase genes is liver specific and is essential for systemic homeostasis; heat-shock gene expression is generic to all cells and important for intracellular homeostasis.

Acute-Phase Proteins↗
PubMed1988

Botulinum toxin therapy for squint.

Four hundred and five patients have been treated with injections of Botulinum neurotoxin A to extraocular muscles in the Botulinum Toxin Clinic at Moorfields Eye Hospital from November 1982 until the present. The indications and outcome of therapy are described and discussed.

Adolescent↗
PubMed1987

The diagnosis and surgical management of acquired bilateral superior oblique palsy.

Thirty-four patients with surgically treated bilateral superior oblique palsy are presented. The patients are divided into three groups: Symmetrical palsies, Asymmetrical palsies, A group in whom the bilaterality was initially masked. Bilaterality should be suspected in all cases of traumatic IVth nerve paresis, and particularly in cases with a large 'V' pattern, excyclo deviation of more than 10 degrees on down-gaze and when right hypertropia switches to left hypertropia on lateral down-gaze. Bilateral Harada-Ito procedures alone 'cured' 11 of 17 patients (65 per cent) in groups 1 and 2, and is the operation of choice in acute bilateral superior oblique palsy. Cyclo deviation was reduced by a mean of 5.5 degrees in the primary position and by 6-10 degrees in down-gaze. Patients initially managed with other surgery had a more complicated surgical course and required more operations. Seven patients who initially demonstrated only gross fusion recovered good fusion after Harada-Ito surgery.

Adolescent↗
PubMed1987

Retinal detachment following Nd:YAG posterior capsulotomy.

Five hundred and eighty-two patients who underwent Nd:YAG laser posterior capsulotomy at Moorfields Eye Hospital were reviewed retrospectively. Twelve patients (2 per cent), nine of whom were previously myopic, subsequently developed rhegmatogenous retinal detachment. Comparison with other studies suggests there is no greater risk of retinal detachment associated with Nd:YAG laser capsulotomy than with surgical discission. The relevance of the damage mechanisms of Nd:YAG lasers are discussed.

Eye Diseases↗
PubMed1985

Aphakic retinal detachment.

A study of 132 cases of aphakic retinal detachment (ARD) following mainly intracapsular cataract surgery has been made. Forty-nine cases (37%) were found to have vitreous incarcerated into the cataract section out of a total of 54 (41%) cases who had suffered a vitreous complication during cataract surgery. A study of the characteristics of ARD reveals that those cases having had a vitreous complication in the management of their cataracts are more likely to develop detachment within three months than those not suffering from such a complication. The occurrence of these early post-extraction retinal detachments is not influenced by the presence of underlying axial myopia. When we compared ARD in patients whose cataract extractions had been complicated by vitreous incarceration with those ARDs following uncomplicated cataract surgery, we found that the characteristics of the detachments were very similar. Thus distribution of underlying myopia, extent of detachment, length of time of detachment, and multiplicity and type of retinal holes were generally similar. However, ARD following complicated cataract surgery is more likely to suffer from periretinal fibrosis. The findings confirmed the risk of ARD following complicated intracapsular cataract surgery and support the tendency to perform the extracapsular operation.

Aged↗
PubMed1985

Carnitine and glucuronic acid conjugates of pivalic acid.

The [1-14C]pivaloyloxyethyl ester of methyldopa administered to man and cynomolgus monkeys resulted in the elimination in the urine of 14C-pivalic acid metabolites. Pivaloyl glucuronide and pivaloyl carnitine were identified as the major radioactive urinary metabolites in monkey urine and human urine, respectively. N.m.r. analysis indicated that pivaloyl carnitine had a cyclic structure. Although the role of carnitine is in the transport of fatty acids across mitochondrial membranes, it may also function in the conjugation of carboxylic acid xenobiotics in humans.

Animals↗
PubMed1984

Sensitive high-performance liquid chromatographic assay using electrochemical detection for a novel prodrug ester of methyldopa, pivaloyloxyethyl 3-(3,4-dihydroxyphenyl)-2-methylalaninate, in plasma and urine.

The pivaloyloxyethyl ester of methyldopa is an antihypertensive prodrug possessing improved bioavailability properties over methyldopa. A sensitive cation-exchange, high-performance liquid chromatographic assay using electrochemical detection has been developed for the ester in plasma and urine in order to determine the extent of its hydrolysis after oral administration. The chromatographic conditions involve two Altex Partisil 10 SCX columns (25 cm X 4.6 mm) in series; a mobile phase consisting of methanol, potassium phosphate buffer, pH 3.0, and EDTA disodium dihydrate; and an electrochemical detector set at 0.5 V. The pivaloyloxyethyl ester in plasma or urine is extracted into ethyl acetate, back-extracted into 0.1 M sulfuric acid, and analyzed directly by high-performance liquid chromatography. For urine, the ethyl acetate extract is washed with a buffer (pH 8.0) prior to the back-extraction step. The assay gives a linear response over the concentration range of 10-160 ng/ml in plasma and 20-400 ng/ml in urine.

Animals↗
PubMed1979

GLC determination of S-2-(3-tert-butylamino-2-hydroxypropoxy)-3-cyanopyridine in human plasma.

S-2-(3-tert-Butylamino-2-hydroxypropoxy)-3-cyanopyridine was recovered (approximately 90%) from human plasma and detected by conversion to a diheptafluorobutyryl derivative for electron-capture GLC. A homolog served as an internal standard. The method measures plasma drug concentrations at the 5-ng/ml level and is suitable for plasma analysis from humans who receive a therapeutic oral dose.

Antihypertensive Agents↗
PubMed1975

Further studies on the metabolism of carbidopa, (minus)-L-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate, in the human, Rhesus monkey, dog, and rat.

Major urinary metabolites of carbidopa have been identified. Estimates were made based on the recovery or radio activity or by glc analysis of pooled urine of the amounts of the urinary metabolites II (2-methyl-3'-methoxy-4'-hydroxyphenylpropionic acid), III (2-methyl-3,4-dihydroxyphenylpropionic acid), IV (3,4-dihydroxyphenylacetone), V [2-methyl-3-(3'-methoxy-4'-hydroxyphenyl)lactic acid], VI [2-methyl-3-(3',4-dihydroxyphenyl)lactic acid], and VII (3-hydroxy-alpha-methylphenylpropionic acid). Metabolite II represented similar to 10% of the urinary radioactivity in both man and monkey and 16% in the dog. Metabolite III represented 10, 17, and 19% of the urinary radioactivity in man, monkey, and dog. Metabolite IV represented smaller than 5% of the urinary radioactivity in human and dog. Metabolite VII represented similar to 10% of the urinary radioactivity in man and monkey. The corresponding figure for the rat was similar to 20%. In the dog, compounds V and VI represented smaller than 5% of the urinary radioactivity. It was concluded that the loss of the hydrazine functional group(probably as molecular nitrogen) represents the major metabolic pathway for carbidopa.

Animals↗
PubMedDate not supplied

Carcinoid tumor of the hepatic duct presenting as a Klatskin tumor in an adolescent and review of world literature.

This is a case presentation of a 14-year-old boy with the radiological diagnosis of cholangiocarcinoma occluding the hepatic duct bifurcation. His only symptom at presentation was jaundice and further workup confirmed a mass at the porta hepatis. Surgical treatment resulted in a resection of the hepatic bifurcation tumor with a final pathological diagnosis of a carcinoid tumor of the hepatic duct bifurcation. To our knowledge, this is only the second case presented of a resected carcinoid tumor in adolescence. In this communiqué we present the above case and review of the world literature of biliary neuroendocrine tumors.

Adolescent↗
PubMedDate not supplied

Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug.

The biosynthesis of cholesterol is mainly regulated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Because the liver is the major site of cholesterol synthesis, it is the primary target of the class of drugs known as HMG-CoA reductase inhibitors. Simvastatin (SV) is a lactone prodrug which undergoes reversible metabolism. In the hydroxy acid form (SVA) it is a potent inhibitor of HMG-CoA reductase. SV is well absorbed by rats, dogs, and humans. After an oral dose of SV, tissue distribution studies were consistent with high hepatic extraction of SV and relatively poor tissue penetration of SVA. The majority of a radioactive dose of SV is eliminated in bile. A high portal/systemic gradient for 6'-OH-SVA, an active biliary metabolite, suggests its probable reentry and indicates potential for prolongation of HMG-CoA reductase inhibition. AUC comparisons in dogs after simultaneous iv (3H) and intraportal (14C) infusions indicate that hepatic extraction is high with only 8% of SV reaching the systemic circulation unchanged. Approximately 98% and 96% of SV was bound to human and dog plasma protein, respectively. The physiological disposition of SV in dog appears to be a suitable paradigm for man. Because of its high hepatic extraction SV should be both specific and selective with respect to the inhibition of HMG-CoA reductase.

Animals↗