Biomedical subjects

S Shelley

Publications and source records attributed to S Shelley.

At least 19 recordsLinked to original sources

PubMed2006

Lymphoscintigraphy as a diagnostic tool in patients with lymphedema of filarial origin--an Indian study.

Lymphedema is a common clinical problem. Filariasis is the commonest cause of lymphedema in India and is a chronic debilitating disease. The purpose of this study is to highlight the role of lymphoscintigraphy in the evaluation of lymphedema. Our study population consisted of 418 patients diagnosed with filarial lymphedema of different clinical stages referred for lymphoscintigraphy of the limbs by the lymphologist at our institution. An analysis of the various studies was done to determine how lymphoscintigraphy can be useful in documentation of the diagnosis, evaluation, as a screening procedure to prevent progression, and to enhance management of filarial lymphedema.

Adolescent↗

PubMed2004

A placebo-controlled crossover study comparing the effects of nateglinide and glibenclamide on postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes.

AIM: This was a randomized, double blind, three period crossover study. The objective was to compare glucose, insulin and C-peptide 24 h profiles in patients with type 2 diabetes mellitus after dosing with nateglinide (given preprandially before three test meals), glibenclamide (administered once before breakfast) or placebo (given before three test meals). METHODS: Fourteen patients underwent screening followed within 3 weeks by three treatment periods of 1 day, each separated by 7 days. Dosing followed a six-sequence balanced, two 3 x 3-replicated Latin square. RESULTS: Mean peak serum insulin levels were lower after nateglinide (115 mU/l) than after glibenclamide (145 mU/l.h; p = 0.017) but higher than after placebo (79 mU/l; p = 0.001). However, peak insulin levels were reached earlier after nateglinide [mean time to peak (tmax) 1.7 h] compared to glibenclamide (mean tmax 2.1 h, p = 0.06). Total insulin exposure over the day was higher after glibenclamide compared with that following nateglinide (1216 vs. 1067 mU/l.h; p = 0.009). Similar findings were seen with serum C-peptide. Despite this, mean peak plasma glucose concentrations were lower following nateglinide (11.4 mmol/l from a baseline of 8.3 mmol/l) compared with glibenclamide (13.2 mmol/l from a baseline of 8.5 mmol/l; p = 0.001) and placebo (14.0 mmol/l from a baseline of 8.0 mmol/L; p < 0.001). CONCLUSIONS: Nateglinide improves early prandial measures of insulin and glucose response to a standard meal, more so than glibenclamide, in people with type 2 diabetes.

Aged↗

PubMed2004

Safety of AT-1015, a novel 5-HT2A antagonist, in combination with high-dose aspirin: an open-label study.

OBJECTIVE: To assess the safety of AT-1015 in combination with high-dose aspirin (300 mg daily). Study subjects were 17 healthy male volunteers. METHODS: This was an open-label, single-center study. Subjects received aspirin 300 mg once daily, alone on days 1-4, and together with AT-1015 40 mg twice daily on days 5-11. A follow-up assessment was performed on day 18. The primary outcome measure was bleeding time; secondary outcome measures were vital signs, adverse events, physical examinations, 12-lead electrocardiograms (ECG) and laboratory safety tests. RESULTS: There was a significant increase in bleeding time between screening and the end of the aspirin-only period (mean bleeding time 4.8 vs 7.6 min, p = 0.01), but there were no further significant increases during the combination treatment period. The most common adverse events were dry mouth, epistaxis, gingival bleeding and abdominal pain. All treatment-related adverse events were mild in severity and no major bleeding episodes occurred. There were no clinically significant changes in vital signs, physical examinations, 12-lead ECGs or laboratory safety tests. CONCLUSIONS: AT-1015 was safe and well-tolerated in healthy male volunteers when taken in combination with high-dose aspirin, and did not significantly prolong bleeding time compared with aspirin alone.

Administration, Oral↗

PubMed2003

Adenosine myocardial SPECT--its efficacy and safety and correlation with coronary angiogram.

OBJECTIVE: The aim of this study was to determine the safety and efficacy of adenosine Tc99m sestamibi myocardial perfusion study under controlled conditions and to correlate the adenosine Tc99m sestamibi perfusion defects and the coronary angiography in patients investigated for coronary artery disease. METHODS: This prospective study included 122 consecutive patients who underwent adenosine Tc99m sestamibi single photon emission computed tomography (SPECT) myocardial perfusion study. Seventy two patients had coronary angiographic correlation. All the patients who were referred by the cardiologists for stress myocardial perfusion scan who could not be stressed physiologically for one reason or the other were included in the study. RESULTS: Among the coronary angiography group the overall sensitivity, specificity, positive predictive value and negative predictive value of adenosine Tc99m sestamibi single photon emission computed tomography myocardial perfusion study for detecting significant coronary obstruction (diameter > or = 50%) were 94.4%, 79%, 85% and 92% respectively. The side effects were transient and required no treatment. CONCLUSION: We conclude adenosine Tc99m sestamibi single photon emission computed tomogram myocardial perfusion study is a reliable test with high sensitivity and specificity for the detection of coronary artery disease.

Adenosine↗

PubMed2002

A 3-way crossover study to evaluate the pharmacokinetic interaction between nateglinide and diclofenac in healthy volunteers.

OBJECTIVE: To assess in healthy male volunteers (n = 18) the effect of diclofenac, a non-steroidal anti-inflammatory analgesic drug used for treatment of rheumatic diseases, on the pharmacokinetics of nateglinide, a new oral hypoglycemic agent that acts by a novel therapeutic mechanism to stimulate insulin release. The effects of nateglinide on the pharmacokinetics of diclofenac were also investigated. METHODS: This open-label study was conducted as a randomized, 3-period, 6-sequence, crossover investigation consisting of 2 reference treatment periods (diclofenac 75 mg or nateglinide 120 mg, alone) and 1 test period (concomitant nateglinide and diclofenac). On the days when nateglinide was administered, subjects received a 120 mg dose at the start of the study day and a second 120 mg dose 4 h after the first. A 2 to 7-day washout interval separated each of the study periods. Nateglinide and diclofenac plasma concentrations were determined up to 12 and 24 h, respectively. RESULTS: Administration of diclofenac did not alter the pharmacokinetics of nateglinide in healthy subjects. Similarly, concurrent administration of nateglinide with diclofenac did not alter the pharmacokinetics of diclofenac in these subjects. All treatments were considered to have been both safe and well tolerated. CONCLUSIONS: These data indicate that concomitant administration of diclofenac with nateglinide does not significantly alter the pharmacokinetic profile of either drug.

Adult↗

PubMed2001

Usefulness of concomitant nitrate administration for the enhancement of viability detection with myocardial perfusion imaging.

Myocardial viability assessment is crucial in the evaluation of patients who had prior myocardial infarction for revascularisation procedures. Conventional methods include nuclear myocardial perfusion imaging, dobutamine stress echocardiography and positron emission tomography. Utility of nitrate in assessment of viability was assessed. Twenty-five patients with prior myocardial infarction underwent 99mTc-sestamibi single photon emission computed tomography protocol of stress, rest and post 5 mg sublingual isorbide dinitrate. The mean age of the patients was 51.28 years. Eight (32%) had reduction in perfusion defect and increased tracer uptake following nitrate administration. It is concluded that addition of nitrate adds to utility of conventional perfusion imaging in the assessment of myocardial viability.

Adult↗

PubMed1997

Reengineering in behavioral medicine.

Shifting demographics, local market issues and new strategic priorities precipitated an examination of operations at a large midwestern hospital. In this context, the Department of Behavioral Medicine embarked upon an intensive, structured process to reengineer its therapeutic model and operating systems. The principal objective of the redesign effort was a shift in the department's orientation from an intrapsychic inpatient paradigm to one that was short-term, crisis intervention-focused and fully integrated with community resources.

Continuity of Patient Care↗

PubMed1995

The implementation of first-trimester scanning at 10-13 weeks' gestation and the measurement of fetal nuchal translucency thickness in two maternity units.

The aim of this prospective screening study was to evaluate the implementation of an additional ultrasound examination, incorporating the measurement of fetal nuchal translucency thickness, at 10-13 weeks' gestation in two maternity units providing routine antenatal care. During the 1 year prior to the introduction of the first-trimester scan, the major indication for fetal karyotyping was maternal age > or = 35 years and only two out of the total of 11 cases of trisomy 21 were identified. In the first 5 months of the study, 70% of the women delivering in these hospitals attended for measurement of fetal nuchal translucency thickness and the measurement was obtained in all cases. This was achieved without an increase in the number of sonographers or ultrasound machines. The incidence of fetal nuchal translucency thickness > or = 2.5 mm was 3.6% (63 of 1763), and this group included three of the four fetuses with trisomy 21. The findings of this study demonstrate the feasibility of introducing scanning at 10-13 weeks' gestation and the measurement of fetal nuchal translucency thickness in routine maternity units. The sensitivity and specificity of this method of screening are at present being evaluated in a large multicenter study.

Abortion, Legal↗

PubMed1994

Acute necrotizing myopathy of intensive care: electrophysiological studies.

A series of recent reports have identified cases of a quadriplegic myopathy characterized by myofiber necrosis and loss of myosin filaments associated with the use of nondepolarizing muscle blocking agents and glucocorticoids. We report electrophysiological findings in 7 intensive care unit patients who developed evidence of an acute myopathy in association with the use of nondepolarizing muscle blocking agents. Several important features were identified: (i) a neuromuscular transmission deficit was observed in 3 patients up to 7 days following withdrawal of vecuronium; (ii) motor M potentials were of low amplitude, there was mild abnormal spontaneous activity on needle electromyography, and sensory conduction was relatively preserved; (iii) not all patients received glucocorticoids or were asthmatic; (iv) 2 patients given vecuronium had very high creatine kinase levels and developed acute renal failure associated with myoglobinuria; and (v) rises in motor M potentials accompanied clinical recovery. This complication of intensive care may be severe, but is reversible and possibly avoidable. Our findings implicate nondepolarizing muscle blocking agents in the development of the myopathy. Electrophysiological studies provide important prognostic guidance.

Action Potentials↗

PubMed1994

Accuracy and reliability of temperature measurement by instrument and site.

The accuracy and reliability of three instruments (IVAC, [IVAC Corp., San Diego, CA] TempaDOT [PyMaH Corp., Somerville, NJ], off-the-shelf glass) were determined at axillary, oral and rectal sites taken on children by experienced RNs given one of three levels of inservice education. TempaDOT was found to be the most clinically valid temperature measurement instrument for 502 children in this acute care setting.

Adolescent↗

PubMed1992

The effects of a high sodium diet on the metabolism and secretion of vasoactive intestinal peptide in the rabbit.

1. In view of previous observations that the metabolism of vasoactive intestinal peptide (VIP) is significantly increased in sodium-depleted rabbits, we wished to determine whether a high sodium intake also leads to alterations in VIP metabolism. We performed metabolic clearance studies in rabbits maintained on a high sodium diet and normal control diets. These studies were performed both before and after the administration of 1.5 mmol kg-1 of sodium intravenously to observe the effects of an acute increase in body sodium. 2. The rabbits maintained on the high sodium diet had a significantly lower basal plasma VIP level (P less than 0.025), a lower metabolic clearance rate (MCR) of the peptide (P less than 0.025) and a lower secretion rate (P less than 0.005), compared with the normal control animals. These differences were maintained following the intravenous sodium infusion. 3. The administration of the intravenous sodium infusion resulted in a further decrease in MCR in the rabbits on the high sodium diet (P less than 0.05). 4. These results confirm that VIP metabolism is affected by high dietary intake of sodium, as well as a low sodium intake, adding further support to the hypothesis that VIP may be involved in sodium homeostasis.

Animals↗

PubMed1991

Oral sodium regulates extrahepatic metabolism of vasoactive intestinal peptide.

1. Gastric sodium loading causes release of vasoactive intestinal peptide from the gastrointestinal tract and, in rabbits on a low-sodium diet, an apparent decrease in metabolism of vasoactive intestinal peptide by the liver. Other workers have shown that decreased hepatic metabolism of vasoactive intestinal peptide is accompanied by an increase in pulmonary metabolism of vasoactive intestinal peptide. To determine whether oral sodium loading also regulates non-hepatic metabolism of vasoactive intestinal peptide, metabolic clearance studies of intravenously infused vasoactive intestinal peptide were performed. These studies were performed in male New Zealand White rabbits equilibrated on normal- and low-sodium diets before and after an acute gastric sodium load of 1.5 mmol/kg. 2. The metabolic clearance rate of vasoactive intestinal peptide was significantly greater in rabbits on the low-sodium diet than in rabbits on the normal-sodium diet both before (P less than 0.025) and after (P less than 0.05) a gastric sodium load. Significant decreases in metabolic clearance rate were observed in response to the sodium load in both dietary groups (normal-sodium diet, P less than 0.05; low-sodium diet, P less than 0.025). The theoretical secretion rate of vasoactive intestinal peptide also fell after the gastric sodium load in rabbits on the low-sodium diet (P less than 0.05) and the half-life of vasoactive intestinal peptide increased (P less than 0.01). 3. We conclude that the non-hepatic metabolism of vasoactive intestinal peptide appears to be responsive to both chronic dietary sodium intake and acute gastric sodium loading.

Administration, Oral↗

PubMed1991

Acute but not chronic gastric sodium administration regulates vasoactive intestinal peptide metabolism by the liver.

We have shown previously that gastric sodium loading releases vasoactive intestinal peptide from the intestine and in rabbits on a low sodium diet it appears to decrease vasoactive intestinal peptide metabolism by the liver. To determine the contributions of the low sodium diet and the acute sodium load to changes in vasoactive intestinal peptide metabolism, metabolic clearance studies of vasoactive intestinal peptide infused intraportally were performed. These studies were performed in male New Zealand white rabbits equilibrated on normal and low sodium diets before and after an acute gastric sodium load of 1.5 mmol kg-1. No difference was detectable in metabolic clearance rates between normal and low salt diets, however, decreases in metabolic clearance rates were observed in response to the sodium load (normal diet P less than 0.005, low salt P less than 0.0005). Secretion rates also decreased following the gastric sodium load (normal P less than 0.005, low salt P less than 0.05). We conclude that hepatic VIP metabolism is decreased by acute gastric sodium loading but it is not affected by chronic sodium intake.

Animals↗

PubMed1990

High-frequency stimulation of the facial nerve results in local cortical release of vasoactive intestinal polypeptide in the anesthetised cat.

Local cortical release of vasoactive intestinal polypeptide (VIP) was measured using a sensitive radioimmunoassay following direct electrical stimulation of the facial nerve in the anaesthetised cat. During activation of the facial nerve dilator pathway VIP was released at the cortex and collected into a physiological superfusate, its concentration increasing from 4.2 +/- 1.2 to 15.5 +/- 2.4 pmol/l. Administration of the nicotinic ganglion blocking agent hexamethonium (10 mg/kg i.v.) eliminated this response demonstrating that the release is mediated via an autonomic ganglion. Given previous experiments that have demonstrated that stimulation of the facial nerve leads to a neurogenically mediated dilatation of the cerebral vasculature, these data further implicate VIP as the transmitter in this pathway.

Animals↗

PubMed1990

Regulation of vasoactive intestinal peptide release and metabolism by sodium.

To determine whether vasoactive intestinal peptide (VIP) might act as a humoral mediator for a proposed portal or hepatic sodium monitor, we measured plasma VIP levels and urinary sodium excretion after portal and intravenous sodium loading in rabbits equilibrated on normal and low sodium diets. Sodium excretion was significantly less after intravenous (2 h: p less than 0.005; 4 h; p less than 0.005; 8 h; p less than 0.025) than after portal sodium administration in rabbit on a low-sodium diet. Plasma VIP levels fell after intravenous (p less than 0.005) but not after intraportal sodium in this group. To determine whether this fall in VIP levels reflected increased metabolism or decreased secretion, metabolic clearance studies were performed in rabbits on a low sodium diet. The metabolic clearance rate of VIP and its theoretical secretion rate increased after intravenous sodium loading in rabbits on a low salt diet (MCR, p less than 0.025; SR, p less than 0.05). We conclude, therefore, that in rabbits on a low-salt diet, intravenous sodium increases VIP metabolism, causing a decrease in plasma levels that may explain the difference in sodium excretion.

Animals↗

PubMed1989

Sodium depletion decreases hepatic metabolism of vasoactive intestinal peptide in the rabbit.

1. Reports that a greater natriuresis occurs after gastric rather than intravenous sodium loads suggest that a gastric sodium monitor exists which releases a humoral natriuretic factor. As vasoactive intestinal peptide (VIP) is natriuretic, it might act as this mediator. To determine whether it released from the gut in response to sodium we measured VIP levels in portal and systemic plasma of anaesthetized rabbits after a gastric sodium load. Levels of VIP in systemic plasma were also measured in conscious rabbits after gastric and portal sodium loads to determine the contributions of anaesthesia or increased sodium concentration in the portal tract to any observed rise in systemic VIP levels. 2. In the anaesthetized rabbit study portal and systemic VIP levels had both increased significantly from control values by 5 min after the sodium load in the low salt diet group (P less than 0.025, portal: P less than 0.05, systemic). By 10 min the levels in systemic and portal plasma were equal. 3. In the conscious rabbits an increase in systemic VIP levels was observed in the group on a low salt diet after a gastric but not a portal sodium load. 4. We conclude that VIP is released in response to gastric sodium loads in rabbits on low salt diets and that hepatic metabolism of VIP is reduced in this group.

Animals↗

PubMed1988

Controlled trial of enalapril in patients with chronic fluid overload undergoing dialysis.

About one third of patients receiving dialysis for end stage renal failure have chronic fluid overload despite advice to restrict their oral fluid intake. To investigate the potential of an angiotensin converting enzyme inhibitor in reducing the urge to drink and consequent gain in weight, a double blind, placebo controlled crossover trial of enalapril was conducted in 25 patients receiving dialysis who had fluid overload. The trial comprised a baseline period of four weeks; two periods of treatment, each of four weeks, during which patients received either placebo or enalapril 5 mg twice each week; and a follow up period of four weeks. Five patients withdrew from the trial, one because of an adverse drug reaction to enalapril. A range of biochemical and behavioural variables was measured during the baseline period, at the completion of periods 1 and 2, and during follow up. These variables included gain in weight between dialysis sessions; blood pressure; plasma concentrations of sodium, angiotensin II, and vasopressin; plasma renin and angiotensin converting enzyme activities; osmolality; and estimations of thirst, intake of fluid, and control of drinking. Enalapril caused a significant reduction in gain in weight between dialysis sessions, thirst, and oral intake of fluid in parallel with significantly increased renin activity, significantly decreased angiotensin converting enzyme activity, and decreased concentrations of angiotensin II. Gain in weight and angiotensin converting enzyme activity returned to baseline values once patients stopped taking enalapril. These results suggest that enalapril may act on the renin-angiotensin system and reduce intake of fluid by inhibiting angiotensin converting enzyme.

Blood Pressure↗

PubMed1981

Isolation, characterization and localization of a 45 000 molecular weight, soluble glycoprotein from the lung in pulmonary alveolar proteinosis.

A carbohydrate-rich, water-soluble glycoprotein has been isolated in pure form from delipidated lung lavage fluid from a patient with pulmonary alveolar proteinosis, in a three-step procedure involving ion-exchange and gel filtration chromatography. The molecular weight of the glycoprotein was determined to be 45 900 by sedimentation equilibrium analysis in the analytical ultracentrifuge and 45 000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, indicating a single polypeptide chain. Nearly half of the mass of the glycoprotein is comprised of carbohydrate that is contributed by 24 residues sialic acid, 23 residues N-acetylglucosamine, 6 residues N-acetylgalactosamine, 19 residues galactose, 4 residues mannose, 1 residue fucose and 1 residue glucose per mol. Unlike a number of collagen-related glycoproteins that have been isolated by others from insoluble lung contents in pulmonary proteinosis, the water-soluble glycoprotein described in the present report does not contain hydroxyproline or hydroxylysine and contains less than 10% of its amino acid residues as glycine. Using rabbit antibodies directed against our purest preparation of material and an immunoperoxidase staining procedure, the 45 000 molecular weight glycoprotein was localized to the thin film of fluid lining the surfaces of alveoli in normal human lungs.

Amino Acids↗