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Biomedical subjects

P Shah

Publications and source records attributed to P Shah.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes.

Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol x kg(-1) x min(-1)) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal (1.21 +/- 0.15 vs. 1.32 +/- 0.19 mol/l per 6 h) and prandial (0.56 +/- 0.14 vs. 0.56 +/- 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 +/- 0.3 vs. -3.1 +/- 0.2 micromol/kg) and prandial (-3.1 +/- 0.4 vs. -3.0 +/- 0.6 pmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.

Blood Glucose↗
PubMed2000

Constraints on using the dual-task methodology to specify the degree of central executive involvement in cognitive tasks.

The dual-task paradigm has been used to examine the role of the central executive in various cognitive tasks. In these studies, performance decrements in primary cognitive tasks performed concurrently with secondary executive tasks have been interpreted as evidence for the involvement of the central executive in those primary tasks. In the present study, we examined the effects of different secondary tasks on performance of three psychometric visuospatial tasks. The decrement in performance of these tasks when they were paired with secondary executive tasks was smallest for the psychometric task considered to most heavily involve the central executive and largest for the task considered least demanding of executive mechanisms. We propose that, when applied to the assessment of central executive involvement, the prevalent simple dual-task logic does not always apply. Special conditions that limit the application of the dual-task methodology include two inherently related factors--a response selection bottleneck and a strategic tradeoff between primary and secondary tasks.

Adult↗
PubMed1999

Frequent allelic loss and homozygous deletion in chromosome band 8p23 in oral cancer.

Frequent loss of heterozygosity on chromosome 8p in a variety of human malignancies, including head and neck cancers, has suggested the presence of a tumor suppressor gene (or genes) associated with the pathogenesis of these cancers. To test the role of genetic alterations at 8p23 in oral carcinogenesis, we studied 51 squamous cell carcinomas of the head and neck and 29 oral squamous cell carcinoma cell lines for allelic loss using 7 microsatellite markers spanning approximately 5 cM of chromosome band 8p23. Twenty-three of 51 tumors (45%) and 23 of 29 cell lines (79%) showed allelic loss at 1 or more loci. Three cell lines showed homozygous deletion of loci within a 3 cM region defined by the markers D8S1781 and D8S262. Our results suggest that a tumor suppressor gene (or genes) is located in 8p23 and is associated with the development and/or progression of oral carcinomas.

Carcinoma, Squamous Cell↗
PubMed1999

Radial artery harvest technique, use and functional outcome.

OBJECTIVE: To develop a simple harvest technique for radial artery (RA). To investigate the morbidity and functional outcome of RA harvest. METHODS: The neurovascular fascia surrounding the RA is divided. Only loose areolar tissue surrounds this artery making harvest of RA simple and allowing minimal trauma to the RA and surrounding muscles. Topical and intraluminal vasodilators but no systemic vasodilators are used. RESULTS: RA harvest commenced in December 1994. Between 1996 and 30 June 1998, 2167 RA were harvested and used to construct 3105 coronary anastomoses. A dramatic rise in RA use occurred during 1996. More than 80% of patients undergoing coronary artery bypass surgery (CABG) have RA harvested since this time. Total arterial revascularization rate also rose dramatically and is currently 80% of all CABG. This rate has been assisted by a rapid rise in the use of composite arterial grafting where aortic anastomoses can be avoided and currently represents 40% of all CABG. Hand strength was tested in 328 non-selected patients and was not reduced by RA harvest when hand dominance was taken into account. Objective sensation loss was present in 0.3% for the superficial radial nerve and 2.1% for the lateral cutaneous nerve of forearm. Pulse oximetry observations detected statistically significant but clinically irrelevant differences. Scar hypersensitivity occurred in 20%. Only two patients of all patients undergoing RA harvest reported late hand ischaemia. CONCLUSIONS: Harvest of the RA within the neurovascular plane is simple and associated with low morbidity.

Aged↗
PubMed1999

Solitary adult myofibroma of the pinna.

Solitary myofibroma is a recently described benign neoplasm of the skin or superficial soft tissue and it represents the adult counterpart of infantile myofibromatosis. This new clinicopathological entity is being recognized increasingly. A case of solitary myofibroma occurring in the pinna of a 50-year-old woman is presented. Such a lesion occurring in the pinna of an adult has not been reported in the literature.

Ear Neoplasms↗
PubMed1999

Portal systemic shunting of insulin does not lead to insulin resistance in patients with extrahepatic portal vein obstruction.

There is no clear relation between portal systemic shunting, reduced hepatic insulin extraction leading to an increased systemic delivery of insulin, and, resultant peripheral hyperinsulinemia and insulin resistance. Extrahepatic portal vein obstruction is a natural human model of portal systemic shunting with essentially normal liver function. To investigate the role of portal systemic shunting of insulin in creating systemic hyperinsulinemia and insulin resistance, we studied nine subjects with portal systemic shunting and nine controls matched for age (+/- 2 years), body weight (+/- 2 kg) and height (+/- 5 cm). We carried out an oral glucose tolerance test and hyperinsulinemic euglycemic clamp study at insulin infusion rate of 40 mU/m2/ min. Comparable (p = 0.61) basal insulin concentrations in the two groups (Mean (SE): 21.0 (3.98) vs. 24.1 (4.28) mU/L) demonstrated a lack of hyperinsulinemia in the presence of portal systemic shunting. The lower (p = 0.03) insulin area under curve on oral glucose tolerance test in presence of portal systemic shunting (7.40 (0.95) vs. 10.83 (1.15) U/L-min) indicated that lower extraction of insulin by the liver leads to a lower requirements in the periphery. The coefficient of variation for plasma glucose between 60 and 120 min of the clamps was 4.44 (0.55)%. Comparable (p = 0.82) M-values (6.21 (0.67) vs. 6.38 (0.45) mg/kg/min) in the two groups proved a lack of significant insulin resistance in the presence of portal systemic shunting. We conclude that isolated portal systemic shunting leads to neither hyperinsulinemia nor insulin resistance.

Adult↗
PubMed1999

Effect of PTU treatment on histone acetylation pattern in the developing rat brain.

The effect of hypothyroidism induced m female rats on histone acetylation pattern m the neonatal rat brain was studied. It is likely that thyroid hormone regulates the acetylation of histones and thereby influence their interaction with DNA and modulates transcription. Propylthiouracil (PTU), administered to induce hypothyroidism, resulted in a significant reduction m the thyroid and brain weight of neonatal rats. The circulating thyroxine levels were undetectable in both 14 and 21 day old pups. The hypothyroid condition was further confirmed by low levels of T4 (94.31 ng/g brain tissue vs 1811.29 ng/g in controls and 144.67 ng/g vs 1087.72 ng/g in controls at 14 and 21 days, respectively) and T3 (42.19 ng/g brain tissue vs 879.97 ng/g in controls and 60.62 ng/g vs 766.68 ng/g in controls at 14 and 21 days, respectively) in the neonatal rat brain. Histone acetylation pattern was similar in treated and control groups m the 14 day old rats. PTU treatment, however, resulted in significant (p<0.01) reduction in acetylation in the H3 fraction at 21 days whereas no such changes were recorded in other histone fractions. Lower histone acetylation in the 21 day old pups suggest a reduction m the transcriptional activity due to fewer initiation sites for RNA polymerase. It may be concluded that thyroid hormone may stimulate transcription of specific genes by increasing the acetylation of nucleosomal histones.

Acetylation↗
PubMed1999

Surgical management of endometrial adenocarcinoma using laparoscopically assisted staging and treatment.

BACKGROUND: Because of inaccuracies in clinical staging, endometrial adenocarcinoma is now a surgically staged disease. This study was done to determine the safety and efficacy of a laparoscopically assisted approach in the treatment and staging of this disease. METHODS: Using a retrospective chart review, we identified demographic characteristics, mean blood loss, operative findings, and complications of patients who had laparoscopically assisted staging and treatment for endometrial carcinoma from 1992 to 1997. RESULTS: Of 34 patients, 28 had laparoscopic surgical staging that included pelvic and para-aortic lymph node assessment, peritoneal washings, bilateral salpingo-oophorectomy, and total vaginal hysterectomy; 23 patients (82%) had stage I disease, 2 (7%) had stage II disease, and 3(11%) had stage III disease. Complications included herniation through a 5 mm port site, necessitating small bowel resection, and a fatal myocardial infarction 10 days postoperatively. CONCLUSION: Laparoscopic staging and treatment of endometrial carcinoma is appropriate in a select group of patients.

Adenocarcinoma↗
PubMed1999

Serum insulin and lipid profile in normal pregnant and pregnancy-induced hypertensive women from North India.

High serum insulin and lipoproteins have been reported in pregnancy-induced hypertension. Little is known about the insulin and lipoprotein profile in Indian women. To address this question we compared serum insulin and lipoproteins of women with pregnancy induced hypertension (PIH) and normotensive pregnant women. The serum insulin, triglycerides, total cholesterol and HDL cholesterol of 104 women with PIH were compared with 99 control women. Hypertensive women had significantly higher insulin (53.94 +/- 29.58 versus 37.69 +/- 17.39 pmol/L, p=0.0004) and triglyceride (3.27 +/- 1.2 versus 2.66 +/- 0.6, p=0.0001). There was no significant difference in total cholesterol and HDL cholesterol levels. Insulin levels had a positive correlation with systolic blood pressure (r=0.64) and diastolic blood pressure (r=0.55) in women with PIH. These differences persisted even after adjusting for possible confounding variables such as age, body mass index and the period of gestation. We conclude that elevated serum insulin values or insulin resistance may contribute to the pathogenesis of PIH in Indian women.

Adult↗
PubMed1999

Impact of lack of suppression of glucagon on glucose tolerance in humans.

People with type 2 diabetes have defects in both alpha- and beta-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a "prandial" glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic (n = 10) or diabetic (n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng. kg(-1). min(-1), beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the "diabetic" insulin profile, lack of glucagon suppression resulted in a marked increase (P < 0.002) in both the peak glucose concentration (11.9 +/- 0.4 vs. 8.9 +/- 0.4 mmol/l) and the area above basal of glucose (927 +/- 77 vs. 546 +/- 112 mmol. l(-1). 6 h) because of impaired (P < 0.001) suppression of glucose production. In contrast, during the "nondiabetic" insulin profile, lack of suppression of glucagon resulted in only a slight increase (P < 0.02) in the peak glucose concentration (9.1 +/- 0.4 vs. 8.4 +/- 0.3 mmol/l) and the area above basal of glucose (654 +/- 146 vs. 488 +/- 118 mmol. l(-1). 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

Adult↗
PubMed1999

Effect of overnight restoration of euglycemia on glucose effectiveness in type 2 diabetes mellitus.

The ability of glucose to stimulate its own uptake and suppress its own release is impaired in type 2 diabetes. To determine whether glucose effectiveness is improved by short term euglycemia, 10 type 2 diabetic subjects were studied on 2 occasions. Insulin was infused throughout the night to maintain euglycemia (approximately 5 mmol/L), or glucose was permitted to remain at ambient hyperglycemic levels (approximately 10 mmol/L) until the following morning when euglycemia was achieved with a variable insulin infusion. A prandial glucose infusion (containing 35 g glucose) was started at 1000 h, and the variable insulin infusion was replaced by a constant infusion of insulin (0.25 mU/ kg x min), somatostatin (60 ng/kg x min), glucagon (0.65 ng/kg x min), and GH (3 ng/kg x min) to maintain hormone concentrations at constant basal levels. Although nocturnal glucose concentrations were (by design) higher (P<0.01) on the hyperglycemic than on the euglycemic study day (10.1+/-0.2 vs. 5.4+/-0.1 mmol/L), glucose concentrations did not differ either before (4.9+/-0.1 vs. 4.9+/-0.1 mmol/L) or during the prandial glucose infusion (peak, 11.1+/-0.5 vs. 11.3+/-0.5 mmol/L; incremental area, 1390+/-254 vs. 1409+/-196 mmol/L x 6 h). Furthermore, glucose-induced stimulation of glucose disappearance (2068+/-218 vs. 1957+/-244 micromol/kg x 6 h) and suppression of glucose production (-2253+/-378 vs. -2124+/-257 micromol/kg x 6 h) did not differ. Thus, restoration of euglycemia by means of an overnight insulin infusion does not alter glucose effectiveness in people with type 2 diabetes.

Blood Glucose↗
PubMed1999

Graves' Disease during pregnancy--results of antithyroid drug therapy.

AIM OF STUDY: To assess the maternal and fetal outcome of pregnancies in thyrotoxic women. METHOD: Thyrotoxic women who conceived while on treatment or who conceived within two years after stopping treatment, were recruited into the study. The antithyroid drugs (PTU and methimazole) dosage were adjusted to keep T3 and T4 within the upper normal range for these women. Cord blood and baby's blood (between days 4 and 10) were assayed for T3, T4 and TSH. RESULTS: Thirteen women (16 pregnancies) required antithyroid drugs during pregnancy. The drug dosage remained the same during pregnancy in 8 women while it was increased in 5 women and reduced in 3 women. One woman who was in remission at the time of conception remained euthyroid throughout her pregnancy. There were 14 spontaneous vaginal deliveries and 3 Caesarean sections. One baby had a small VSD while no other congenital malformations or perinatal death occurred. CONCLUSIONS: Drug therapy can adequately control thyrotoxicosis during pregnancy and improve maternal and fetal outcome.

Adult↗
PubMed1999

HSV-1 migration in latently infected and naive rabbits after penetrating keratoplasty.

PURPOSE: To investigate the migration of herpes simplex virus type 1 (HSV-1) between latently infected and naive corneal tissues and trigeminal ganglion (TG) in rabbits after penetrating keratoplasty (PKP) and transcorneal epinephrine iontophoresis. METHODS: Two mutants, genetically constructed from HSV-1 strain 17syn+, were used to inoculate rabbit corneas: 17deltaPst, a latency associated transcript (LAT) negative, low-reactivating virus and 17Pr, a high-reactivating, LAT-positive rescuant of 17deltaPst. Latently infected rabbits were given corneal allografts from naive rabbits, and naive rabbits received grafts from latently infected rabbits. Ninety days after PKP, groups of the transplanted rabbits were induced to reactivate by transcorneal epinephrine iontophoresis, but others were not induced. Viral shedding was monitored by tear film cultures. Rabbits were killed 5 days after iontophoresis. Transplanted grafts, recipient corneal rims, and corresponding TG were obtained. Nucleic acids were extracted and amplified for detection of HSV-1 DNA and viral gene transcription. RESULTS: In naive rabbits receiving grafts transplanted from rabbits latently infected with 17Pr (LAT+), 3 of 6 corneal rims contained HSV DNA after induction. In contrast, none of the 5 corneal rims from naive rabbits receiving grafts from rabbits latent with 17deltaPst (LAT-) contained viral DNA. Viral DNA and gene transcripts were detected in 2 of 6 TG from naive rabbits that received grafts from 17Pr (LAT+) latently infected rabbits. In recipient corneal rims and TG of latently infected rabbits receiving grafts from naive rabbits, viral DNA concentration was significantly greater with induced reactivation, compared with the results in noninduced rabbits. The amount of viral DNA in naive grafts transplanted into 17Pr (LAT+) latently infected rabbits was significantly higher with induction than without induction (P = 0.018). More viral DNA and viral gene transcripts were found in tissues from rabbits latently infected with 17Pr (LAT+) than in rabbits latently infected with 17deltaPst (LAT-). CONCLUSIONS: Corneas from latently infected rabbits contain HSV-1 DNA that can replicate after induced reactivation. Viral migration can occur in both anterograde and retrograde directions between the transplanted graft and the recipient corneal rim and TG. The LAT negative HSV-1 construct 17deltaPst has a significantly reduced ability to replicate and migrate.

Animals↗
PubMed1999

Mapping and positional cloning of common idiopathic generalized epilepsies: juvenile myoclonus epilepsy and childhood absence epilepsy.

Among the 40 to 100 million persons with epilepsy worldwide and the 2 to 2.5 million persons with epilepsies in the United States, approximately 50% have generalized epilepsies. Among all epilepsies, the most common are juvenile myoclonus epilepsy (JME) with 10% to 30% of cases, childhood absence epilepsy (CAE) with 5% to 15% of cases, and pure grand mal on awakening with 22% to 37% of cases. In the last decade, six different chromosomal loci for common generalized epilepsies have been identified. These include two separate loci for JME in chromosomes 6p and 15q. The epilepsy locus in chromosome 6p expresses the phenotypes of classic JME, pure grand mal on awakening, and possibly JME mixed with absences. Two separate loci also are present for pyknoleptic CAE, namely, CAE that evolves to JME in chromosome 1p and CAE with grand mal in chromosome 8q24. Pandolfo et al. from the Italian League Against Epilepsy have reported two other putative susceptibility loci for idiopathic generalized epilepsies, namely, grand mal and generalized spike waves 35l in chromosome 3p and generalized epilepsies with febrile convulsions, grand mal, JME, absences, and electroencephalographic spike waves in 8q24. This chapter reports on the debate concerning whether there may be two separate epilepsy loci in chromosome 6p, one in the HLA region and one below HLA. The chapter then discusses the progress made in our laboratories as a result of the Genetic Epilepsy Studies (GENES) International Consortium. We discuss (a) the 2 to 6 cM critical region for classic JME located some 20 cM below HLA in chromosome 6p, (b) the 7-cM area for pyknoleptic CAE that evolves to JME in chromosome 1p, and (c) the 3.2 cM area for pyknoleptic CAE with grand mal and irregular 3 to 4 Hz spike waves in chromosome 8q24. We discusses efforts underway to refine the genetic map of JME in chromosome 6p11 and the advances in physical mapping and positioning of candidate genes, such as the gamma-aminobutyric acid receptor gene, the potassium channel gene of the long-QT family (KvLQT), named KCNQ3, and the human homologue of the mouse jerky gene for CAE in chromosome 8q24 and JME in chromosome 6p11.

Chromosome Mapping↗