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Biomedical subjects

S Vickers

Publications and source records attributed to S Vickers.

At least 19 recordsLinked to original sources
PubMed2006

Tinted contact lenses as an alternative management for photophobia in stationary cone dystrophies in children.

BACKGROUND: Intense photophobia is a debilitating symptom of the stationary cone dystrophies. The dark-tinted glasses with side-shields and floppy hats used to manage this are very conspicuous and can cause marked psychological morbidity to the children and their families. We assess the use of tinted contact lenses as an alternative management for the photophobia. METHODS: Three children, aged 5 to 13, with cone dystrophies, all with markedly reduced visual acuity, color vision, and profound photophobia were fitted with Lunelle ES70 Solaire 70% brown contact lenses. The child's parents completed two Children's Visual Function Questionnaires, the first pertaining to the period when the child wore tinted glasses; the second pertaining to the period of tinted contact lens wear. RESULTS: Subjectively, two of the children and their parents described a striking improvement in their quality of life, with improved confidence, interactions with other children, and cessation of name-calling and bullying. The Children's Visual Function Questionnaires gave objective evidence for this improvement in one child and was not significantly different in the other. The third child was reluctant to wear the contact lenses despite her parents' active encouragement. CONCLUSION: Tinted contact lenses offer an alternative management of the photophobia associated with stationary cone dystrophies in children. Marked improvements in their quality of life were observed in this case series.

Adolescent↗
PubMed2006

Contamination of disposable tonometer prisms during tonometry.

AIM: Due to the theoretical possibility of prion transmission in applanation tonometry, many ophthalmological units in the United Kingdom now use disposable tonometer prisms. We have investigated the potential for bacterial and viral transmission from the health practitioner to the patient via disposable prisms. METHODS: All staff who perform applanation tonometry at the Sussex Eye Hospital (SEH) received a questionnaire to evaluate if the applanating face of the prism is touched during tonometry and the ease of use of the disposable prism compared to the reusable prisms that were previously used. We then cultured prisms handled by a random sample of staff members for common bacteria. Finally, we constructed a model to investigate the possibility of interpatient adenoviral transmission via disposable tonometer prisms. RESULTS: The questionnaire revealed that almost 50% of the staff admit to touching the applanating face of the tonometer prism prior to applanation. Cultures of the prisms grew a range of bacteria including Staphylococcus epidermidis, Staphylococcus aureus, and Bacillus species. The viral model suggested that adenovirus could be transmitted by applanation tonometry. CONCLUSION: The use of disposable prisms for applanation tonometry may reduce the risk of prion transmission but is not bacteriologically or virologically aseptic. This is a potential infection risk to patients.

Adenoviridae↗
PubMed2002

Fetal surveillance in pregnancy complicated by diabetes mellitus: is it necessary?

This article provides a literature review and opinion concerning the need for fetal surveillance in diabetic pregnancy. Low rates of intervention for suspected fetal jeopardy accompany well-controlled diabetic pregnancies in the absence of vascular disease or hypertension. The clinical utility of routine tests of fetal surveillance in uncomplicated type 1 and type 2 diabetic and gestational diabetic pregnancy has not been established. A randomized trial designed to establish whether a benefit exists to fetal testing in this population is not feasible, largely owing to sample size considerations.

Blood Glucose Self-Monitoring↗
PubMed2001

Improved reduction in pain in chronic pancreatitis with combined intraoperative celiac axis plexus block and lateral pancreaticojejunostomy.

PURPOSE:Severe abdominal pain secondary to chronic pancreatitis is often multifactorial in origin. Lateral pancreaticojejunostomy (LPJ) is currently the accepted surgical treatment of choice when the main pancreatic duct is dilated. Chemical ablation of the celiac plexus for the treatment of intractable pain in chronic pancreatitis has been used without clear benefit. The aim of this study is to compare treatment outcomes of 2 groups of patients with the diagnosis of chronic pancreatitis and intractable abdominal pain (LPJ alone versus LPJ with intraoperative alcohol celiac ablation).Between 1994 and 1997, 34 patients underwent LPJ to control intractable pain secondary to chronic pancreatitis. These patients were divided into 2 groups, group 1 was LPJ only (16 patients) and group 2 was LPJ and intraoperative celiac ablation with 50% absolute alcohol (18 patients). Preoperative diagnosis and treatment criteria were similar for both groups. The clinical characteristics and outcome of both groups were retrospectively analyzed. Fisher exact test was used for statistical analysis.Demographic characteristics were similar in both groups. Pain control at short- and long-term follow-up was significantly improved in group 2 compared with group 1 (p < 0.035).Intraoperative celiac ablation in addition to LPJ appears to have a better response than does LPJ alone. Even though the number of patients is small, these results provide a basis for pursuing a prospective, randomized study to definitively answer this question.

Journal Article↗
PubMed2000

The biotransformation of nitrogen containing xenobiotics to lactams.

The metabolism of nitrogen heterocyclics may lead to lactam formation. In early studies on xenobiotic metabolism lactams were identified as metabolites of nicotine, cyproheptadine, tremorine and prolintane. Now, because of the increasing availability of powerful analytical techniques, there are many instances of lactams being identified as metabolites. Lactam metabolites are formed from either iminium ions or carbinolamines. These two intermediates may have distinct mechanisms of formation but they can interconvert. There is evidence that the iminium ions are oxidized to lactams by aldehyde oxidases (cytosolic molybdenum hydroxylases). The tissue distribution and enzyme activities of aldehyde oxidase have been studied in several animal species. However, it is also known that iminium ions can undergo spontaneous hydrolysis to the corresponding carbinolamine. If the latter is stable it may undergo oxidation by cytochrome P-450 to form the lactam. Thus, species differences in lactam formation might be caused by differences in the concentrations of either cytochrome P450 isozymes or aldehyde oxidases. It appears that lactam formation is an end stage in the metabolism of N-heterocycles in that it is unlikely that the lactam will undergo hydrolysis to the corresponding amino acid. Such amino acids probably arise from the amino aldehydes that may be produced from ring opening of unstable carbinolamine intermediates. When microsomal preparations are incubated with the appropriate substrate in the presence of sodium cyanide the iminium ion may be trapped to produce a cyano compound. Such reactions have led to the proposal that iminium ions might react with nucleophilic sites of cellular macromolecules and so contribute to both the pharmacology and toxicology of N-heterocyclic compounds. Other pathways for the formation of lactam metabolites involve the internal cyclization of precursor metabolites, e.g. the self-condensation of an aldehyde group (formed during metabolism) with a neighboring amide group. However, spontaneous ring closures of amino acids to form lactams seem unlikely since it would be anticipated that the amino acid residue would exist as a stable zwitterion under physiological conditions. Thus, it is unlikely that lactams will undergo futile metabolism via hydrolytic ring opening followed by ring closure. Under extreme conditions such unanticipated ring closures may occur and the conditions of metabolite isolation may contribute to the occurrence of artifacts.

Animals↗
PubMed1999

Hypotensive ischemic optic neuropathy and peritoneal dialysis.

PURPOSE: To report anterior ischemic optic neuropathy associated with systemic hypotension in a patient undergoing continuous ambulatory peritoneal dialysis. METHODS: Case report. A 58-year-old man undergoing continuous ambulatory peritoneal dialysis developed painless blurred vision in both eyes and bilateral optic disk swelling with an altitudinal field defect in the left eye. Twenty-four-hour ambulatory blood pressure monitoring was requested in addition to other routine investigations. RESULTS: Routine blood pressure measurement in the clinic was 130/86 mm Hg, but ambulatory blood pressure monitoring demonstrated pronounced early morning hypotension with individual readings as low as 91/41 mm Hg. CONCLUSIONS: Renal dialysis can render patients hypotensive, and this may be associated with anterior ischemic optic neuropathy. The overnight drop in blood pressure may not be appreciated with routine blood pressure measurement. Therefore, 24-hour ambulatory blood pressure monitoring should be considered when investigating patients with suspected anterior ischemic optic neuropathy who are undergoing renal replacement.

Blood Pressure↗
PubMed1999

In vitro and in vivo studies on the metabolism of tirofiban.

Tirofiban hydrochloride [L-tyrosine-N-(butylsulfonyl)-O-[4-(4-piperidinebutyl)] monohydrochloride, is a potent and specific fibrinogen receptor antagonist. Radiolabeled tirofiban was synthesized with either (3)H-label incorporated into the phenyl ring of the tyrosinyl residue or (14)C-label in the butane sulfonyl moiety. Neither human liver microsomes nor liver slices metabolized [(14)C]tirofiban. However, male rat liver microsomes converted a limited amount of the substrate to a more polar metabolite (I) and a relatively less polar metabolite (II). The formation of I was sex dependent and resulted from an O-dealkylation reaction catalyzed by CYP3A2. Metabolite II was identified as a 2-piperidone analog of tirofiban. There was no evidence for Phase II biotransformation of tirofiban by microsomes fortified with uridine-5'-diphospho-alpha-D-glucuronic acid. After a 1 mg/kg i.v. dose of [(14)C]tirofiban, recoveries of radioactivity in rat urine and bile were 23 and 73%, respectively. Metabolite I and unchanged tirofiban represented 70 and 30% of the urinary radioactivity, respectively. Tirofiban represented >90% of the biliary radioactivity. At least three minor biliary metabolites represented the remainder of the radioactivity. One of them was identified as I. Another was identified as II. When dogs received 1 mg/kg i.v. of [(3)H]tirofiban, most of the radioactivity was recovered in the feces as unchanged tirofiban. The plasma half-life of tirofiban was short in both rats and dogs, and tirofiban was not concentrated in tissues other than those of the vasculature and excretory organs.

Animals↗
PubMed1998

Development of orally active oxytocin antagonists: studies on 1-(1-[4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2- methoxybenzoyl]piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines.

The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors. Incorporation of a 5-fluoro substituent on the central benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo potency but was detrimental to the pharmacokinetic profiles of these compounds. Although lipophilic substitution around the pyridine ring of compound 30 gave higher affinity in vitro, such substituents were a metabolic liability and caused shortfalls in vivo. Two approaches to prevent this metabolism, addition of a cyclic constraint and incorporation of trifluoromethyl groups, were examined. The former approach was ineffective because of metabolic hydroxylation on the constrained ring system, whereas the latter showed improvement in plasma pharmacokinetics in some cases.

Administration, Oral↗
PubMed1998

Metabolism of MK-499, a class III antiarrhythmic agent, in rats and dogs.

MK-499 [(+)-N-[1'-(6-cyano-1, 2, 3, 4-tetrahydro-2(R)-naphthalenyl)-3, 4-dihydro-4(R)-hydroxyspiro(2H-1-benzopyran-2, 4'-piperidin)-6-yl]methanesulfonamide] monohydrochloride is an investigational class III antiarrhythmic agent for treatment of malignant ventricular tachyarrhythmias. The disposition of [3H]MK-499 and [14C]MK-499 was studied in rats and dogs after oral and iv administration. MK-499 was concentrated in organs of excretion and the heart. In the rat, urinary radioactivity elimination values after iv (0.5 mg/kg) and oral (6.25 mg/kg) doses were 21 +/- 3% and 10 +/- 2%, respectively. Corresponding fecal recoveries were 68 +/- 6% and 78 +/- 7%. Similar results were found after corresponding doses of [14C]MK-499. In dogs, urine and feces accounted for 16 +/- 3% and 75 +/- 4% of recovered radioactivity after a [3H]MK-499 iv dose (0.1 mg/kg). Corresponding recoveries after an oral dose (1 mg/kg) were 12 +/- 2% and 76 +/- 3%. Biliary (0-24 hr) excretion accounted for 39 +/- 5% and 41 +/- 18% of [3H] and [14C] oral doses in rats, respectively. Dogs excreted 34% of [3H] oral dose in (0-24 hr) bile. The data indicated that a substantial amount of MK-499 was absorbed by rats and dogs. MK-499, metabolite I (formed by loss of N-substitution), and metabolite II (an acid formed by metabolic scission across the benzopyran ring) each represented 30% of rat urinary label. Rat bile contained MK-499 (10%), II (20%), and IV (10%), which was formed by carbon-4 hydroxylation of the tetralin ring. Additionally, rat bile included glutathione (V) and N-acetyl-1-cysteine (VI) conjugates of a ring-opened metabolite. Metabolite III, a positional isomer of IV, was excreted in rat urine. The major labeled species excreted in dog bile were unchanged MK-499 and its glucuronide (VII), which, respectively, represented 50% and 30% of the biliary radioactivity. MK-499 and a small amount of I represented dog urinary radioactivity. The bioavailability of MK-499 was high in dogs (100%) but low in rats (17%). This difference was probably due to the more extensive presystemic metabolism of MK-499 in rats.

Animals↗
PubMed1998

Immunoaffinity localization of the enzyme xanthine oxidase on the outside surface of the endothelial cell plasma membrane.

BACKGROUND: Reactive oxygen metabolites generated from endothelial xanthine oxidase (XO) trigger reperfusion injury in many organs. We evaluated the possibility that endothelial XO was localized on the endothelial cell surface, as well as within the cytoplasm. METHODS: Primary cultures of bovine (BAECs) and porcine (PAECs) aortic endothelial cells were grown in media documented to be free of XO. Polyclonal and monoclonal antibodies were developed against XO. These antibodies were used to evaluate BAEC and PAEC for cell surface XO through immunofluorescence staining, hybridoma cell surface labeling, and endothelial cell surface binding. RESULTS: These antibodies bound specifically to the surface of these cells when the membrane was shown to be intact and impermeable (and the cytoplasm inaccessible) to immunoglobulins Moreover, hybridoma cells expressing monoclonal antibody to XO bound specifically to the endothelial cell surface. Finally, intact endothelial cells bound specifically to the anti-XO polyclonal antibodies immobilized to the surface of a Petri dish. The integrity of these endothelial cell plasma membranes was demonstrated by the subsequent growth and replication of these cells in culture. CONCLUSIONS: These findings indicate that XO is present on the outside surface of the endothelial cell plasma membrane. This would not only explain the known in vivo efficacy of intravascularly administered large molecular weight antioxidants (such as superoxide dismutase) but could have important implications for inflammatory signaling.

Animals↗
PubMed1994

Duplication of the 15q11-13 region in a patient with autism, epilepsy and ataxia.

Various developmental abnormalities can give rise to the clinical syndrome of autism, and some are due to chromosomal anomalies. One syndrome has been identified in which behavioural disorder is associated with the clinical features of epilepsy and ataxia, and with the chromosomal anomaly of an extra marker chromosome containing a duplication of 15q11-13. The authors report a boy with autism, epilepsy, ataxia and an interstitial duplication of 15q, in whom molecular analysis reveals duplication of the GABRA5 and GABRB3 genes on the maternally derived chromosome.

Ataxia↗
PubMed1992

Mesenteric vasoconstriction in cardiogenic shock in pigs.

The quantitative impact of mesenteric vasoconstriction on the systemic hemodynamic response to cardiogenic shock induced by pericardial tamponade was evaluated. Graded increases in pericardial pressure produced corresponding decreases in cardiac output to 44% +/- 2% and arterial pressure to 64% +/- 3% of baseline and increases in total peripheral vascular resistance to 131% +/- 4% of baseline. Total mesenteric blood flow decreased disproportionately, to 28% +/- 3% of baseline, because of a disproportionate increase in mesenteric vascular resistance to 223% +/- 6% of baseline. Nonmesenteric vascular resistance increased only to 119% +/- 4% of baseline. Thus mesenteric vasoconstriction accounted for 42% of the increase in total peripheral resistance. Prior blockade of the renin-angiotensin axis ablated this response and eliminated the mesenteric contribution to systemic vascular resistance, while confirmed blockade of the alpha-adrenergic system or vasopressin system had no effect. Without shock, central intravenous infusions of angiotensin II (but not norepinephrine or vasopressin) closely mimicked this selective vasoconstriction. Angiotensin-mediated selective mesenteric vasoconstriction accounts for more than 40% of the overall increase in systemic vascular resistance in cardiogenic shock.

Animals↗
PubMed1991

Studies on the metabolic inversion of the 6'chiral center of simvastatin.

In two simvastatin (SV) metabolites the 6' alpha-methyl of SV is oxidized to either 6' beta-CH2OH (I) or 6' beta-COOH (II). A possible intermediate is 6' exomethylene SV (III). When Sprague Dawley rats received an i.v. dose of [14C] III (1 mg/kg) metabolite II was excreted in bile. When dogs received an i.v. dose of [14C] III together with either [3H] SV (1 mg/kg) or its hydroxy acid form, [( 3H] SVA) (10 mg/kg), both 3H and 14C I and II were excreted in bile. These results strongly indicate that I and II are secondary metabolites of SV formed from III perhaps via a common aldehyde intermediate.

Animals↗