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Biomedical subjects

J H Shah

Publications and source records attributed to J H Shah.

At least 19 recordsLinked to original sources
PubMed1998

Glycemic index and insulin response to a liquid nutritional formula compared with a standard meal.

OBJECTIVE: To determine the glycemic index and metabolic responses to a nutritional formula, and to compare these responses to those following an oral glucose meal and a standard test meal. METHODS: Six male and six female healthy non-diabetic volunteers aged 18 to 48 years met screening examination and laboratory assessment criteria. Three test meals were administered, each containing 50 g of carbohydrate: nutritional formula (NF), standard test meal (ST) and a glucose test meal (GT). Each subject underwent the three test meals on separate days in randomized sequence. Blood samples were taken at intervals over 5 hours for determination of glucose, insulin and triglycerides. RESULTS: The glycemic index was similar for the NF (60.8 +/- 13.1) and for the ST (57.8 +/- 12.9) meals. The incremental area under the curve for glucose was similar for NF and ST, but each was significantly lower than for the GT meal. The total area under the curve for insulin was significantly greater for the NF meal than for the ST meal. The serum triglyceride responses were similar for NF and ST meals. CONCLUSION: In healthy non-diabetic subjects, the blood glucose and triglyceride responses are similar for a nutritional formula compared to an isoenergetic standard test meal. However, the insulin response differs. This information is important in managing tube-fed patients.

Adolescent↗
PubMed1997

Tin-117m(4+)DTPA: pharmacokinetics and imaging characteristics in patients with metastatic bone pain.

UNLABELLED: Biokinetics and imaging characteristics of 117mSn(4+)DTPA have been studied in patients with metastatic bone pain. METHODS: Seventeen patients with bone pain due to metastasis were given three dose levels: 180 microCi/kg (6.66 MBq/kg), 229 microCi/kg (8.47 MBq/kg) and 285 microCi/kg (10.55 MBq/kg) body weight. Periodic blood and daily urine samples were collected for 14 days to measure percent injected activity retained in blood and that excreted in urine. Simultaneous anterior and posterior view whole-body images were obtained under identical scan settings at 1, 3.5 and 24 hr and on Days 3 and 7 and between 4-6 and 8-10 wk postinjection. The total body retention was calculated using the geometric mean counts. RESULTS: After intravenous injection, the total body clearance of 117mSn(4+)DTPA shows two components: a soft-tissue component and a bone component. The soft-tissue component accounts for 22.4% of the dose and consists of four subcomponents with an average biologic clearance half-time of 1.45 days (range 0.1-3.2 days). The bone component accounting for the remaining 77.6% of the dose shows no biologic clearance. A mean 22.4% of the dose is excreted in urine in 14 days; 11.4% within 24 hr. The uptake pattern appears similar to that of 99mTc-MDP. Peak uptake is observed in normal bone by 24 hr and metastatic lesions by 3-7 days. Pain palliation was observed with all three doses levels. CONCLUSION: Among the four potential bone pain palliation radionuclides, 117mSn(4+)DTPA demonstrates the highest bone uptake and retention. Some biokinetic and radionuclidic features of 117mSn(4+)DTPA are similar to other agents, but many features are different and unique and may make it an ideal bone pain palliation agent. Double-blind comparative studies are needed to determine its exact role in bone pain palliation.

Adult↗
PubMed1996

(+/-)-3-[4'-(N,N-dimethylamino)cinnamyl]benzazepine analogs: novel dopamine D1 receptor antagonists.

Neurochemical studies and structure-activity relationships of dopamine D1 receptor ligands suggest that their intrinsic activity may depend on the conformational state or binding site at which they interact on the receptor protein. Important differences in the modes of binding of these ligands may confer their agonist, partial agonist, or antagonist properties. In an effort to develop novel dopamine D1 antagonists and investigate the D1 antagonist pharmacophore, a series of (+/-)-(N-alkylamino)benzazepines were prepared in which (+/-)-7-chloro-8-hydroxy-3-[6-(N,N-dimethylamino)hexyl]-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine (1) demonstrated the highest binding affinity (Ki = 49.3 nM) and selectivity to dopamine D1 receptors. This compound inhibited dopamine-stimulated adenylyl cyclase, in rat caudate, confirming a D1 receptor antagonist profile. From this initial series of N-alkylamino-substituted benzazepines, structure-activity relationships suggested that the terminal amino function was necessary for optimal binding affinity and selectivity at D1 vs D2 sites. Further, addition of this side chain to the D1 agonist pharmacophore (e.g., 7,8-dihydroxy-3-[4-(N,N-dimethylamino)butyl]-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine) greatly decreased binding affinity at D1 receptors. These data suggested that a binding domain that may be unique to the D1 antagonists may have been identified. In an attempt to exploit an apparent amine-accepting binding domain on the D1 receptor, a series of (+/-)-3-[4'-(N,N-dimethylamino)cinnamyl]benzazepine analogs was designed and prepared, as D1 antagonists. In this series, (+/-)-7-chloro-8-hydroxy-3-[4'-(N,N-dimethylamino)cinnamyl]-1-phenyl-2,3,4,5 -tetrahydro-1H-3-benzazepine (6a) showed the highest binding affinity (Ki = 60.3 nM) for dopamine D1 receptors. Compound 6a was a potent dopamine D1 antagonist as evidenced by its ability to block dopamine-stimulated adenylyl cyclase activity in rat caudate (predicted Ki value = 18.4 nM). Molecular modeling studies demonstrated that the most potent and selective dopamine D1 antagonists, in both series, contained terminal amino groups 8-9 A away from the 3-position benzazepine nitrogen. Compounds that lacked a terminal amine function or where this moiety was less than 7 A away from the benzazepine nitrogen demonstrated significantly lower binding affinities. Therefore, this series of (+/-)-3-[4'-(N,N-dimethylamino)cinnamyl]benzazepines also appears to be identifying an amine-accepting binding domain on the dopamine D1 receptor protein that may be further explored for the development of novel dopamine D1 antagonists.

Adenylyl Cyclases↗
PubMed1995

(+/-)-(N-alkylamino)benzazepine analogs: novel dopamine D1 receptor antagonists.

(+/-)-(N-Alkylamino)benzazepine analogs were prepared as novel dopamine D1 receptor antagonists to further elucidate the role of these receptor subtypes in the pharmacology and toxicology of cocaine. In the first series of compounds, (+/-)-7-chloro-8-hydroxy-3- [6-(N,N-dimethylamino)-hexyl]-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepi ne (15) showed the highest affinity (Ki = 49.3 nM) and subtype-selectivity for dopamine D1 over dopamine D2, 5-HT2a, and 5-HT2c receptors. Compounds 7a [(+/-)-7-Chloro-8-hydroxy-3-[4-(N,N-dimethylamino)butyl]-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine], 11 [(+/-)-7-chloro-8-hydroxy-3-[6-[(N,N-dimethylamino)hexyl]-1- phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-cyanoborane], and 15 were moderately potent dopamine D1 receptor antagonists as evidenced by their ability to block dopamine-stimulated adenylyl cyclase activity in rat caudate (predicted Ki values = 60, 34, and 21 nM, respectively). Compound 7a appears to be unique in that, despite its relatively potent inhibition of dopamine stimulated adenylyl cyclase, it demonstrated relatively weak binding affinity at the dopamine D1 receptors (Ki = 811 nM). Unlike previously reported N-alkylbenzazepines, where a significant loss in dopamine D1 receptor binding affinity was observed when successive increases in the alkyl side chain size at the benzazepine nitrogen were made, several of these novel N-alkylamino analogs demonstrated high-affinity binding with an optimal chain length of six carbons. This initial series of compounds appears to be identifying another binding domain on the dopamine D1 receptor protein that has not previously been characterized and that accepts an amino function. Further, these compounds may serve as templates for the design of peripherally active dopamine D1 receptor antagonists.

Animals↗
PubMed1993

Effects of oxazepam on anxiety: implications for Fowles' psychophysiological interpretation of Gray's model.

The present dose-response study investigated the effects of the benzodiazepine oxazepam (Serax) on anxiety as measured by autonomic and self-report indices in a nonclinical sample. Given Fowles' (1980, 1988) theory that electrodermal activity primarily reflects the activity of the behavioral inhibition system (BIS) while heart rate primarily reflects the activity of the behavioral activation system (BAS), we predicted that electrodermal indices of anxiety would be more affected by oxazepam than heart rate. Psychophysiological and self-report measures were recorded prior to and following a speech stressor in subjects given placebo (n = 17), 15 mg oxazepam (n = 19), and 30 mg oxazepam (n = 17). Anxiolytic effects were found during stressed state as measured by skin conductance level but not heart rate or self-reported anxiety. Furthermore, the anxiolytic effects of oxazepam were noted only during the stressful phases of the experiment. The results are viewed as supportive of Fowles' motivational interpretation of the distinction between heart rate and electrodermal responding.

Adolescent↗
PubMed1992

Calcinosis and metastatic calcification due to vitamin D intoxication. A case report and review.

Vitamin D, a fat-soluble vitamin, can be associated with significant morbidity when prescribed in large doses. We describe a hypoparathyroid patient with vitamin D intoxication who developed painful periarticular calcinosis, nephrocalcinosis with hypertension and chronic renal failure in addition to band keratopathy and hearing loss. He was treated with combination therapy including prednisone, phosphate-binding antacid, phenytoin and disodium etidronate. After 20 months of follow-up there was a significant reduction of periarticular calcinosis, but no improvement in renal function, band keratopathy or hearing loss and possible calcification of the ossicles. The clinicopathologic features of metastatic calcification and the various treatment modalities are reviewed.

Adult↗
PubMed1991

Assessment of physician perceptions on the fatality of cancer.

A questionnaire was developed to evaluate internists' perceptions about patients' survival of cancer as compared with other diseases. The questionnaire consisted of four pairs of survival-matched cancer and non-cancer diseases. The questionnaire was administered to 42 faculty members and 37 resident physicians in the Department of Medicine at the University of Missouri-Columbia. Physicians rated patients' survival of cancer to be significantly lower than patients' survival of comparable non-cancer diseases (p less than 0.001). Resident physicians estimated patients' survival of breast cancer to be significantly lower (p less than 0.007) and estimated the survival of lung cancer to be significantly higher than the faculty members' estimate (p less than 0.003). These physicians' perceptions could adversely affect the quality of care and the degree of consideration given to both cancer and non-cancer patients. The differences observed in faculty members' and resident physicians' responses were attributed to the greater knowledge and clinical experience of faculty rather than differences in attitudes toward cancer.

Health Knowledge, Attitudes, Practice↗
PubMed1990

Spontaneous decline in exercise-induced proteinuria during a 100-mile triathlon.

To study the effect of prolonged exercise on glomerular permeability and proteinuria, we collected serial urine samples from six athletes during a 100-mile triathlon. Urine collected just before, at the midpoint of, and immediately after the race was analyzed for creatinine by an automated chemistry analyzer, pack method, and for microalbumin by radioimmunoassay. By midrace, the urinary albumin-creatinine ratio increased from the prerace mean +/- SEM of 3.5 +/- 0.5 to 38.3 +/- 11.7 mg/g. The ratio then declined to 12.5 +/- 2.7 mg/g by the end of the race (P less than .04). Similarly, the urinary albumin level increased significantly from 5.9 +/- 0.7 to 80.5 +/- 26.8 micrograms/mL by midrace, followed by a decline to 39.2 +/- 12.9 micrograms/mL. The initial increase in albuminuria was expected and reflects the increase in exercise-induced cardiac output and glomerular permeability. The subsequent decline in albuminuria and albumin-creatinine ratio, despite continued exercise, was unexpected and indicates a decrease in glomerular permeability. Further study is warranted to determine the mechanism of this apparently protective renal response to prolonged exercise.

Adult↗
PubMed1989

Aspartame and its constituent amino acids: effects on prolactin, cortisol, growth hormone, insulin, and glucose in normal humans.

Because large doses of phenylalanine stimulate prolactin secretion in man, we studied the acute effects of oral doses of aspartame (0.534 g, equivalent to the amount of aspartame in approximately 1 L beverage), aspartic acid (0.242 g), and phenylalanine (0.3 and 1.0 g) on serum prolactin and other hormones in normal humans. Prolactin was not stimulated by any of the aspartame meals, aspartic acid, or 0.3 g phenylalanine; a small rise in serum prolactin, similar to that produced by a high-protein mixed meal, followed ingestion of 1.0 g phenylalanine. Serum growth hormone showed no statistically significant changes in response to any of the experimental meals whereas cortisol and insulin fell slightly and glucose rose slightly during each of the meals. We conclude that these doses of aspartame do not alter secretion of prolactin, cortisol, growth hormone, or insulin in normal individuals.

Administration, Oral↗
PubMed1988

Alcohol decreases insulin sensitivity in healthy subjects.

To study the effect of alcohol on glucose and insulin metabolism, a simultaneous infusion of glucose and insulin was given for 150 min to healthy volunteers, once during alcohol and once during calorie-free gingerale (control) ingestion. During alcohol intake, the average steady-state (between 100 and 150 min) glucose of 5.44 +/- 0.39 mmol/l. and the average steady-state insulin of 6.3 +/- 1.1 ng/ml were significantly higher than those (4.0 +/- 0.39 mmol/l. of glucose and 4.4 +/- 0.6 ng/ml of insulin) observed during the control state. Despite the higher steady-state insulin concentrations, the glucose metabolism was significantly less during alcohol ingestion. These findings suggest alcohol-induced impairment in glucose metabolism is caused by a decreased tissue sensitivity to insulin.

Adult↗
PubMed1987

The effect of vincristine on parathyroid hormone release and on the parathyroid cell microtubular structures in the intact rat.

The effect of vincristine on immunoreactive parathyroid hormone (iPTH) release and parathyroid cell microtubular structures was evaluated in intact, unanaesthetized, and unrestrained rats with indwelling catheters. In overnight fasted rats, blood samples were collected before and at 30, 60 and 120 min after iv vincristine administration in low dosage (0.15 mg/kg) or in higher dosage (0.5 mg/kg) or vehicle (controls) for serum iPTH and calcium determinations. Mean baseline serum iPTH and calcium concentrations were similar in the vincristine-treated and the control rat. Following the low dose vincristine treatment, serum iPTH slightly but significantly declined to 89 +/- 5% at 30 min and remained at this low level at 60 and 120 min as compared to those observed in control rat. Similarly, iPTH concentrations after higher doses of vincristine were also significantly decreased to 87 +/- 4% at 30 min and to 83 +/- 4% at 60 min, and 86 +/- 7% at 120 min as compared to those observed in the control rat. Serum calcium concentrations were similar in the vincristine-treated and control rats. In the next study, each of the rats received vincristine and vehicle in a random order, 10 days apart. In this study also, mean serum iPTH significantly declined to 85 +/- 7% at 60 and 120 min during vincristine treatment as compared with those observed during the vehicle treatment in the same rats. Parathyroid glands were removed from rats between 60 and 120 min after vincristine or vehicle treatments for electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Homicide by insulin administration.

This report describes a case of homicide by insulin administration and a study of the effects of storage conditions on insulin in serum. The study revealed insulin to be remarkably stable at refrigerator temperatures. Therefore, for forensic science purposes, insulin immunoassay data are interpretable even when serum is not stored by the standard laboratory method of freezing.

C-Peptide↗
PubMed1986

Symptomatic reactive hypoglycemia during glucose tolerance test in lithium-treated patients.

Glucose, insulin, glucagon, and cortisol responses during a five-hour oral glucose tolerance test (GTT) were evaluated in nine patients with bipolar affective disorders who were receiving lithium treatment and in seven control patients with bipolar affective disorders who were not receiving any treatment. Both the lithium-treated and the control patients were in stable mood at the time of GTT. During GTT mean nadir serum glucose of 48 +/- 2 mg/dL in the lithium-treated patients was significantly lower (P less than 0.001) than mean nadir serum glucose of 62 +/- 2 mg/dL observed in the control subjects. Seven of these nine lithium-treated patients, but none of the control patients, experienced hypoglycemic symptoms coinciding with low serum glucose concentration. In response to hypoglycemia, mean serum cortisol significantly rose (P less than 0.01) to 22 +/- 3 micrograms/dL in the lithium-treated patients, whereas mean serum cortisol levels gradually declined to 10 +/- 2 micrograms/dL in the control patients at 300 minutes. Despite symptomatic postglucose hypoglycemia, plasma glucagon levels in the lithium-treated patients were similar to those observed in the control patients. These findings suggest that chronic lithium treatment is associated with a symptomatic and biochemical hypoglycemia during GTT, which is characterized by a rise in serum cortisol but by lack of appropriate rise in plasma glucagon concentrations.

Adult↗