Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 73 records · Page 4Linked to original sources

PubMed1997

Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus.

BACKGROUND & AIMS: Marked hyperglycemia slows and hypoglycemia accelerates gastric emptying. The aim of this study was to determine the effect of physiological changes in blood glucose gastric emptying. METHODS: In 8 healthy subjects and 9 patients with insulin-dependent diabetes mellitus (IDDM) without gastrointestinal tract symptoms or evidence of neuropathy, gastric emptying of a mixed meal was measured by scintigraphy. Using an insulin-glucose clamp, the blood glucose concentration was stabilized at 4 and 8 mmol/L on 2 separate days. RESULTS: The intragastric retention of the solid meal component at 100 minutes was 55.2% +/- 4.5% at 8 mmol/L vs. 36.7% +/- 5.5% at 4 mmol/L (P = 0.004) in normal subjects and 44.2% +/- 4.2% vs. 35.7% +/- 4.2% (P = 0.004) in patients with IDDM. The time taken for 50% emptying of the liquid meal was 57.0 +/- 10.8 minutes at 8 mmol/L vs. 32.2 +/- 12.6 minutes at 4 mmol/L (P = 0.002) in normal subjects and 41.3 +/- 3.4 minutes vs. 29.1 +/- 3.5 minutes (P = 0.002) in patients with IDDM. CONCLUSIONS: Changes in blood glucose within the normal postprandial range have a significant impact on gastric emptying in both normal subjects and patients with IDDM.

Adult↗

PubMed1997

Desmopressin for nocturnal incontinence in the spina bifida population.

PURPOSE: We report our experience with the use of desmopressin in the spina bifida population that is dry during the day but wet at night. MATERIALS AND METHODS: From 1994 to 1996, 18 patients with myelodysplasia were treated with desmopressin for persistent nocturnal enuresis. Initial dose was 40 mcg. before bedtime, decreased by intervals of 10 mcg. every 3 weeks. Patients were kept on the minimum dose required to keep them dry. We reviewed morning catheterized volumes, side effects and dosages needed to stay dry, and compared augmented patients with nonaugmented patients. RESULTS: Of 18 patients 14 (78%) reported marked improvement in nocturnal enuresis. Of 6 augmented patients 5 (83%) are dry compared to 9 of 12 nonaugmented patients (75%). There were no adverse side effects from the use of desmopressin. Average dose to stay dry was 20 mcg. for augmented and 30 mcg. for nonaugmented patients. Of the 4 patients who had persistent nocturnal incontinence despite desmopressin 3 (75%) became dry with a single catheterization in the middle of the night. CONCLUSIONS: Desmopressin is successful in treating nocturnal enuresis in the spina bifida patient with diurnal continence.

Adolescent↗

PubMed1997

Body composition and age in African-American and Caucasian women: relationship to plasma leptin levels.

Leptin is a recently isolated peptide hormone released from adipocytes that has been postulated to play a role in appetite regulation and energy metabolism. Aging affects both food intake and body composition. Body composition is also affected by ethnicity. We have evaluated the relationships between serum leptin levels, age, body composition (by dual-energy x-ray absorptiometry), and hormonal parameters in a cross-sectional study of 94 women, 53 African-American (AAF) and 41 Caucasian (CF). Our hypotheses were as follows: (1) changes in body composition would be related to age in a sinusoidal pattern, (2) changes in serum leptin would parallel changes in body fat, (3) serum leptin levels would be influenced by body fat distribution, and (4) serum leptin would be related to serum concentrations of sex hormones. Serum leptin paralleled changes in body fat and body mass index (BMI) with age. In the entire group, serum leptin correlated closely with measures of body fat, including BMI and total fat mass, and there was no difference in leptin levels between the two ethnic groups. In simple regression analysis, serum leptin was related to both serum estradiol and testosterone. The relationship between serum leptin and trunk fat was linear in both groups, but significantly different in AAF and CF (P = .014). Serum leptin was associated with the trunk to lower-extremity fat ratio in CF (r = .67, P = .001) but not in AAF. Body fat was increased with advancing age until about 65 years and then declined. Measures of lean body mass declined linearly with age in the entire group, as well as both subgroups. In the entire group, total lean body mass and lean body mass corrected for BMI (lean body mass/BMI) were inversely related to age. In subjects aged less than 60 years AAF were stronger (P < .05) and had both a larger BMI and fat mass (P < .05) than CF. However, the patterns of age-related changes in fat body mass, lean body mass, and BMI were similar in both groups. In the entire group, multiple regression analysis indicated that the age, free thyroxine index (FTI), and leptin concentration were predictors of the body composition and distribution of trunk to lower-body fat. These observations indicate that there is a sinusoidal relationship between body fat and age, with a decline in body fat in extreme old age in both AAF and CF, and that serum leptin concentrations are more closely related to body fat and BMI than to age or ethnicity.

Absorptiometry, Photon↗

PubMed1997

Gaucher's disease: molecular, genetic and enzymological aspects.

The molecular, genetic and enzymological abnormalities in Gaucher's disease have been delineated during the past decade. Although our understanding of the primary predisposition to the Gaucher's disease phenotypes has improved, the relationships remain poorly understood between the mutant alleles, the resultant enzyme variants, the saposin C (activator protein) locus and phenotypes. Of the more than 100-disease associated alleles, about 8 to 10 have significant frequencies in various ethnic and demographic groups. The N370S(1226G) allele is very frequent in Caucasian populations, but absent in Asian groups. In the Ashkenazi Jewish population, the N370S homozygosity predisposes to Gaucher's disease, but over 50% of such patients escape medical detection because of their mild to absent involvement, i.e. N370S may be a prediposing polymorphic variant. Clarification of genotype/phenotype relationships and the identification of modifier loci that impact on Gaucher's disease phenotypes remain a critical area for research. Greater understanding of these issues will facilitate genetic counselling and appropriate interventive therapy to prevent the morbid long-term manifestations of Gaucher's disease.

Gaucher Disease↗

PubMed1997

Hyperglycemia affects gastric electrical rhythm and nausea during intraduodenal triglyceride infusion.

Hyperglycemia slows gastric emptying and increases the intensity of perception of gastric distension during fasting and small intestinal nutrient stimulation. In order to examine the possibility that abnormalities of gastric electrical rhythm may be associated with the effects of hyperglycemia, the gastric electrical rhythm (cutaneous electrogastrogram) and the perception rating scores for upper gastrointestinal sensations (visual analog scale) were examined. Studies were performed during intraduodenal triglyceride infusion in 10 healthy volunteers under euglycemic and hyperglycemic (approximately 15 mmol/liter) conditions. During fasting, hyperglycemia had no effect on either gastric electrical rhythm or sensation. Intraduodenal triglyceride infusion was associated with an increase in bradygastria (<2.4 cpm) during both euglycemia (33 +/- 9%) and hyperglycemia (36 +/- 10%, P < 0.05 vs baseline for each). During intraduodenal triglyceride infusion, tachygastria (>3.6 cpm) was more prevalent during hyperglycemia when compared to euglycemia (25 +/- 10% vs 1 +/- 1%, P < 0.05) and the perception rating scores for nausea and abdominal discomfort were greater during hyperglycemia (P < 0.05 for both). The intensity of nausea correlated with the proportion of time spent in tachygastria (r = 0.64, P < 0.01). These data are consistent with the concept that postprandial upper gastrointestinal symptoms in patients with diabetes mellitus may be modulated by the blood glucose concentration.

Adult↗

PubMed1997

Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation.

T cell depletion using the murine monoclonal antibody (moAb) T10B9 is unique in that the T cell receptor (TCR)gamma delta bearing subset is relatively spared compared to the TCR alpha beta + subset. We evaluated the probabilities of engraftment, acute and chronic graft-versus-host disease (GVHD), relapse, and survival in 273 recipients of marrow T cell depleted using T10B9. Sixty-two patients received marrow from an HLA-identical sibling, 54 patients received partially matched related donor marrow and 157 patients received unrelated donor marrow. Limiting dilution analysis (LDA) was used to estimate total clonable T cell dose in all patients and a modified LDA using moAb-coated immunomagnetic beads was used to estimate TCR alpha beta +, CD4+, and CD8+ T cells in a subset of patients. TCR gamma delta + cell dose was estimated by flow cytometry. Cox proportional hazards regression models were used to assess the impact of T cell subset dose/kg of body weight on outcome. We found a significant association of TCR gamma delta + T cell dose (P = 0.004), but not TCR alpha beta + T cell dose or total clonable T cell dose, with the probability of engraftment. TCR alpha beta +, CD4+, CD8+ and total clonable T cell dose were significantly associated (P < 0.001) with the risks of grade 2-4 acute GVHD in recipients of marrow from related donors but not in recipients of marrow from unrelated donors. Neither total clonable T cell dose nor any T cell subset dose was found to be significantly associated with chronic GVHD, relapse or survival. The results confirm preclinical studies showing TCR gamma delta + T cells promote engraftment. TCR gamma delta + T cells are not associated with an increased risk of acute GVHD while TCR alpha beta T cells are associated with acute GVHD but not engraftment in recipients of marrow grafts T cell depleted using T10B9. These findings support the hypothesis that T cell subsets differentially contribute to alloengraftment and GVHD.

Adolescent↗

PubMed1997

Measurement of gastric emptying by intragastric gamma scintigraphy.

Gastric emptying is usually measured in animals and humans by dilution/sampling or external scintigraphy. These methods are either time consuming or require expensive equipment. The capacity of a miniature gamma counter positioned in the stomach to measure emptying of liquid and solid meals was evaluated. In eight conscious pigs fitted with gastric and duodenal cannulae, gastric emptying of saline (500 mL), dextrose (20%, 500 mL), porridge (300 g) and scrambled eggs (300 g), all labelled with 3.5 MBq 99mTC, was evaluated. When positioned in the antrum the probe was unable to quantify gastric emptying. In contrast, measurements of the fractional emptying of saline over 4-min periods by the probe positioned in the corpus and quantification of radioactivity in the duodenal effluent correlated closely (r = 0.88, P < 0.05). Gastric emptying (50% emptying time) of saline and both solid meals measured by the probe was not significantly different from quantification of the duodenal effluent volume. No difference was observed also for the dextrose meal but only while gastric acid secretion was suppressed by omeprazole. We conclude that an intragastric gamma counter permits measurement of gastric emptying of homogeneous meals provided meal stimulation of gastric secretion was not extensive. This was possible probably by monitoring emptying from the proximal stomach.

Animals↗

PubMed1997

Physiological variations in blood glucose concentration affect oesophageal motility and sensation in normal subjects.

BACKGROUND/AIMS: A marked elevation in the blood glucose concentration (approximately 15 mmol L-1) slows oesophageal peristalsis. Recent studies indicate that changes in blood glucose within the normal postprandial range affect gastric motility and emptying. The aim of this study was to investigate whether such alterations in blood glucose also affect oesophageal motility. METHODS: In eight healthy subjects oesophageal motility and sensation to balloon distension were measured on two separate days while blood glucose concentrations were stabilized with an insulin-glucose clamp at 4 mmol L-1 and 8 mmol L-1. RESULTS: Peristaltic velocity in the proximal oesophagus and over the oesophagus as a whole was faster at a plasma glucose concentration of 8 mmol L-1 compared with those at 4 mmol L-1 (proximal 3.3 +/- 0.3 cm s-1 vs 2.6 +/- 0.2 cm s-1, P < 0.05, total 3.1 +/- 0.2 cm s-1 vs 2.7 +/- 0.2 cm s-1, P < 0.005) but there were no differences in wave amplitude or duration, or basal lower oesophageal sphincter pressure (LOSP). The threshold for initial perception of oesophageal distension was lower at a plasma glucose of 8 mmol L-1 (2.9 +/- 0.5 mL vs 4.9 +/- 1.0 mL, P < 0.05). CONCLUSIONS: physiological variations in plasma glucose concentration influence oesophageal motility and sensation. These observations suggest that in order to minimize effects of varying plasma glucose levels on oesophageal motility, manometry should be performed under the same fasting or fed conditions when oesophageal motor function is evaluated.

Adult↗

PubMed1997

Relations between calcium intake, calcitriol, polymorphisms of the vitamin D receptor gene, and calcium absorption in premenopausal women.

The relations between calcium absorption, dietary calcium intake, 1,25-dihydroxyvitamin D3 (calcitriol), and vitamin D receptor (VDR) gene polymorphisms were evaluated in 99 healthy women who were approaching menopause (mean age: 47 y, range: 43-53 y). Dietary calcium was assessed by food-frequency questionnaire and calcium absorption was measured by a single-isotope radiocalcium test. VDR alleles were classified according to the presence (b, t, a) or absence (B, T, A) of the BsmI, TaqI, and ApaI restriction enzyme cutting sites. Radiocalcium absorption was positively related to serum calcitriol (r = 0.23, P < 0.05) and inversely related to dietary calcium intake (r = -0.26, P < 0.01). There was, however, no significant relation (r = 0.10) between serum calcitriol concentrations and dietary calcium. Radiocalcium absorption was higher in the bbaaTT haplotype (P < 0.05) and the aa genotype (P < 0.05), polymorphisms said to be associated with a higher bone density. We conclude that serum calcitriol and dietary calcium are independent determinants of calcium absorption in premenopausal women and that VDR gene polymorphisms influence calcium absorption.

Adult↗

PubMed1997

Relation between postprandial satiation and antral area in normal subjects.

The factors influencing appetite in humans are poorly understood. There is a weak relation between appetite and gastric emptying in normal subjects. Recent studies have shown that fasting and postprandial antral areas increase in patients with functional dyspepsia compared with normal subjects. We evaluated the hypothesis that antral area, and hence antral distention, is a significant determinant of postprandial fullness. Fourteen normal subjects had simultaneous measurements of gastric emptying by scintigraphy and antral area by ultrasound after ingestion of 350 mL 20% glucose. Fullness and hunger were assessed by visual analog scales. Measurements of the gastric-emptying half time (t1/2) by scintigraphy and ultrasound were not significantly different (129.6 +/- 11.8 min compared with 115.6 +/- 11.4 min). Fullness increased (P < 0.001) and hunger decreased (P < 0.001) after the drink. Both fullness and the magnitude of the increase in fullness after the drink were related to antral area (r > 0.56, P < 0.05), the increase in antral area (r > 0.59, P < 0.05), and the scintigraphic content of the distal stomach (r > 0.57, P < 0.05), but not to the ultrasound or scintigraphic t1/2 values. In contrast, hunger and the magnitude of the decrease in hunger after the drink were not related to either antral area, the increase in antral area, or the rate of gastric emptying. We conclude that postprandial fullness, but not hunger, was closely related to antral distention in normal subjects.

Adult↗

PubMed1997

Expression of mutated glucocerebrosidase alleles in human cells.

Gaucher disease is a heterogeneous disease characterized by impaired activity of the lysosomal enzyme glucocerebrosidase. This heterogeneity is attributed to a large number of mutations in the corresponding gene. In order to test the biochemical properties of some mutations prevalent among Israeli populations, the normal human glucocerebrosidase cDNA and cDNAs carrying mutations N370S, L444P, D409H, recTL, recNcil, P415R and 84GG were coupled to the T7 RNA polymerase promoter in a vaccinia virus-derived expression vector (pTM-1). Recombinant viruses were produced and used to infect human tissue culture cells. RNA and protein stability, recognition by anti-glucocerebrosidase monoclonal antibodies and intracellular enzymatic activity were measured. The results demonstrated that the D409H allele directed synthesis of cytoplasmic RNA with decreased stability compared with its normal counterpart or other mutated forms. The D409H and L444P mutated proteins had lower stability than that of their normal counterpart, while the recNcil-mutated protein was more stable. Only glucocerebrosidase forms harboring leucine at position 444 were recognized by the anti-glucocerebrosidase monoclonal antibodies used (8E4 and 2C7). Measurements of enzymatic activity of the recombinant proteins in cells loaded with a fluorescent glucosylceramide demonstrated that the N370S mutated enzyme had activity similar to that of the normal enzyme. The other mutated enzymes exhibited varying degrees of activities, generally corresponding to the phenotypes with which they are associated. The results presented demonstrate the use of the vaccinia virus-derived expression system and of loading living cells with fluorescent substrate as efficient tools for studying mutants in Gaucher disease and in other lysosomal diseases.

Alleles↗

PubMed1997

Changes of biological reducing activity in rat brain following closed head injury: a cyclic voltammetry study in normal and heat-acclimated rats.

Reactive oxygen species (ROS) are normally generated in the brain during metabolism, and their production is enhanced by various insults. Low molecular weight antioxidants (LMWA) are one of the defense mechanisms of the living cell against ROS. The reducing capacity of brain tissue (total LMWA) was measured by cyclic voltammetry (CV), which records biological oxidation potential specific to the type of scavenger(s) present and anodic current intensity (Ia), which depends on scavenger concentration. In the present study, the reducing capacity of rat brain following closed head injury (CHI) was measured. In addition, CV of heat-acclimated traumatized rats was used to correlate endogenous cerebroprotection after CHI with LMWA activity. Sham-injured rat brains displayed two anodic potentials: at 350 +/- 50 mV (Ia = 0.75 +/- 0.06 microA/mg protein) and at 750 +/- 50 mV (Ia = 1.00 +/- 0.05 microA/mg protein). Following CHI, the anodic waves appeared at the same potentials as in the sham animals. However, within 5 min of CHI, the total reducing capacity was transiently decreased by 40% (p < 0.01). A second dip was detected at 24 h (60%, p < 0.005). By 48 h and at 7 days, the Ia levels normalized. The acclimated rats displayed anodic potentials identical to those of normothermic rats. However, the Ia of both potentials was lower (60% of control, p < 0.001). The Ia profile after CHI was the direct opposite of the normothermic Ia profile: no immediate decrease of Ia and an increase from 4 h and up to 7 days (40-50%, p < 0.001). We suggest that the lowered levels of LMWA in the post-CHI period reflect their consumption due to overproduction of free radicals. The augmented concentration of LMWA found in the brain of the heat-acclimated rats suggests that these rats are better able to cope with these harmful radicals, resulting in a more favorable outcome following CHI.

Acclimatization↗

PubMed1997

Oxidative stress in closed-head injury: brain antioxidant capacity as an indicator of functional outcome.

It has been suggested that reactive oxygen species (ROS) play a role in the pathophysiology of brain damage. A number of therapeutic approaches, based on scavenging these radicals, have been attempted both in experimental models and in the clinical setting. In an experimental rat and mouse model of closed-head injury (CHI), we have studied the total tissue nonenzymatic antioxidant capacity to combat ROS. A major mechanism for neutralizing ROS uses endogenous low-molecular weight antioxidants (LMWA). This review deals with the source and nature of ROS in the brain, along with the endogenous defense mechanisms that fight ROS. Special emphasis is placed on LMWA such as ascorbate, urate, tocopherol, lipoic acid, and histidine-related compounds. A novel electrochemical method, using cyclic voltammetry for the determination of total tissue LMWA, is described. The temporal changes in brain LMWA after CHI, as part of the response of the tissue to high ROS levels, and the correlation between the ability of the brain to elevate LMWA and clinical outcome are addressed. We relate to the beneficial effects observed in heat-acclimated rats and the detrimental effects of injury found in apolipoprotein E-deficient mice. Finally, we summarize the effects of cerebroprotective pharmacological agents including the iron chelator desferal, superoxide dismutase, a stable radical from the nitroxide family, and HU-211, a nonpsychotoropic cannabinoid with antioxidant properties. We conclude that ROS play a key role in the pathophysiology of brain injury, and that their neutralization by endogenous or exogenous antioxidants has a protective effect. It is suggested, therefore, that the brain responds to ROS by increasing LMWA, and that the degree of this response is correlated with clinical recovery. The greater the response, the more favorable the outcome.

Animals↗

PubMed1997

The management of unilateral poorly functioning kidneys in patients with posterior urethral valves.

PURPOSE: There is no uniform agreement on how to manage the unilateral nonfunctioning or poorly functioning kidney associated with posterior urethral valves. We studied the results of treatment of our patients to make recommendations regarding management of these kidneys. MATERIALS AND METHODS: We reviewed the records of 13 boys with a history of posterior urethral valves and a unilateral nonfunctioning or poorly functioning kidney, defined as less than 10% of total renal function on 99mtechnetium dimercapto-succinic acid renal scans. Variables investigated included pyelonephritis, hypertension, vesicoureteral reflux, nephroureterectomy, ureteral reimplantation and spontaneous cessation of reflux. We also evaluated how the management of abnormal urodynamic parameters influenced the results of reimplantation or medically induced cessation of reflux. RESULTS: Three of the 6 boys with grade 5 reflux ipsilateral to the poorly functioning kidney required nephroureterectomy at a mean age of 21 months because of recurrent urinary tract infections. Another 4 boys underwent successful ureteral reimplantation, including 2 who had bilateral grade 5 reflux, and 2 who had ipsilateral grade 4 reflux, and grade 3 (1) and grade 2 (1) contralateral reflux. Of 4 boys ipsilateral grade 3 reflux in 3 and bilateral grade 5 reflux in 1 disappeared without surgery after treatment of urodynamic abnormalities. Two patients with poorly functioning kidneys and no reflux did not undergo surgery. Overall 10 of the 13 poorly functioning renal units were not removed, and these patients were free of pyelonephritis and hypertension. Ureteral reimplantation (4 ipsilateral and 3 contralateral) was performed only after urodynamic abnormalities were addressed. All reimplantations were successful. CONCLUSIONS: Based on our results we believed that unilateral poorly functioning kidneys in patients with posterior urethral valves can be safely preserved in select patients without hypertension and pyelonephritis. Reimplantation to correct reflux may be preferable to nephroureterectomy in specific situations, such as when contralateral function is suboptimal and the contralateral ureter needs reimplantation. When indicated, reimplantation can be performed successfully if abnormal urodynamic parameters are addressed preoperatively. In fact, treating abnormal urodynamic findings may lead to spontaneous reflux resolution.

Adolescent↗

PubMed1997

Management of posterior urethral valves on the basis of urodynamic findings.

PURPOSE: Abnormal urodynamic findings are common in boys with a history of posterior urethral valves. However, to our knowledge there are few reports on the results of treating these abnormal findings. We analyzed the treatment of abnormal urodynamic parameters and its outcome in 21 boys who underwent valve ablation. MATERIALS AND METHODS: After valve ablation multichannel urodynamic studies were performed in 31 boys, including 21 in whom studies were done before and after therapy was started for abnormal parameters. Detrusor instability and impaired bladder compliance were treated with anticholinergics or augmentation cystoplasty, and impaired detrusor contractility was managed with clean intermittent catheterization. RESULTS: Before therapy 17 of 21 boys had impaired compliance and detrusor instability, 2 had impaired compliance without instability and 2 had instability alone. After treatment 8 boys had impaired compliance and 4 had detrusor instability. After anticholinergics were initiated new onset myogenic failure in 2 boys necessitated clean intermittent catheterization. Of the 13 patients who presented with urinary incontinence 10 became dry and 3 had improvement with therapy. Vesicoureteral reflux in 10 boys at the time of the initial urodynamic study resolved in 7 with anticholinergic medication and in 1 after clean intermittent catheterization was begun for severely impaired compliance. All 21 boys were treated with anticholinergics and 2 were ultimately treated with augmentation cystoplasty. Clean intermittent catheterization was also instituted in 5 patients, including the 2 who required clean intermittent catheterization after myogenic failure developed. Five boys with high voiding pressures were found to have outlet obstruction due to residual valve tissue in 2, bladder neck obstruction in 2 and urethral stricture in 1 despite normal flow rates in 2. CONCLUSIONS: Urodynamic studies are helpful in guiding therapy in boys after valve ablation. Anticholinergic therapy can improve compliance, decrease detrusor instability, improve continence and eliminate vesicoureteral reflux in the majority of boys, although there is an associated risk of myogenic failure. Flow rates and fluoroscopic voiding studies are often unable to detect outlet obstruction and must be obtained in conjunction with voiding pressure measurements to make this diagnosis.

Follow-Up Studies↗

PubMed1997

The effect of cisapride on oral and intravenous glucose tolerance in normal subjects.

Cisapride is used widely for the treatment of diabetic gastroparesis. There is some evidence that cisapride may influence insulin secretion. The aim of this study was to evaluate the effect of cisapride on plasma concentrations of glucose, insulin and C-peptide in response to oral and intravenous glucose loads. Twelve normal subjects took cisapride and placebo, each for 10 days using a randomized, double-blind, crossover design. In each treatment phase, the plasma glucose, insulin and C-peptide response to intravenous (0.5 g/kg) and oral (75 g) glucose loads was evaluated on separate days. Gastric emptying of the oral glucose load was also measured. After the intravenous glucose load, plasma concentrations of C-peptide were higher (P< 0.01) on cisapride when compared with placebo (e.g. peak C-peptide 2.08+/-0.25 nmol/L vs 1.78+/-0.22 nmol/L, P< 0.01) while there was no significant difference in plasma glucose or insulin. Cisapride had no effect on the rate of gastric emptying of the oral glucose load. Mean plasma concentrations of insulin and C-peptide were higher after oral glucose on cisapride than placebo, but these differences were not significantly different. These observations indicate that cisapride may increase glucose-stimulated insulin secretion.

Administration, Oral↗

PubMed1997

Acute hyperglycaemia affects anorectal motor and sensory function in normal subjects.

BACKGROUND: The pathogenesis of anorectal dysfunction, which occurs frequently in patients with diabetes mellitus, is poorly defined. Recent studies indicate that changes in the blood glucose concentration have a major reversible effect on gastrointestinal motor function. AIMS: To determine the effects of physiological changes in blood glucose and hyperglycaemia on anorectal motor and sensory function in normal subjects. SUBJECTS: In eight normal subjects measurements of anorectal motility and sensation were performed on separate days while blood glucose concentrations were stabilised at 4, 8, and 12 mmol/l. METHODS: Anorectal motor and sensory function was measured using a sleeve/sidehole catheter incorporating a balloon, and electromyography. RESULTS: The number of spontaneous anal relaxations was greater at 12 mmol/l than at 8 and 4 mmol/l glucose (p < 0.05 for both). Anal squeeze pressures were less at a blood glucose of 12 mmol/l when compared with 8 and 4 mmol/l (p < 0.05 for both). During rectal distension, residual anal pressures were not significantly different between the three blood glucose concentrations. Rectal compliance was greater (p < 0.05) at a blood glucose of 12 mmol/l when compared with 4 mmol/l. The threshold volume for initial perception of rectal distension was less at 12 mmol/l when compared with 4 mmol/l (40 (20-100) ml versus 10 (10-150) ml, p < 0.05). CONCLUSIONS: An acute elevation of blood glucose to 12 mmol/l inhibits internal and external anal sphincter function and increases rectal sensitivity in normal subjects. In contrast, physiological changes in blood glucose do not have a significant effect on anorectal motor and sensory function.

Acute Disease↗

PubMed1997

Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion.

Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of rats subjected to a combined chronic stress of heat acclimation and swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC), DP, and SP were measured during progressive graded ischemia, total ischemia (TI), and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy. During normoperfusion, SP and cardiac efficiency (derived from rate-pressure product-oxygen consumption relationships) were the highest in the 2-mo EXAC hearts (P < 0.0001). During progressive graded ischemia, the development of IC (percentage of total hearts) was similar in both EXAC and EX hearts; the only significant difference was confined to the 1- vs. 2-mo groups. The onset of IC was delayed in the EXAC hearts and, on reperfusion, recovery, particularly of DP, was significantly improved in the latter. After TI, EXAC hearts retained 30% of the ATP pool and there was a delayed decline in intracellular pH. On reperfusion, these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo EXAC heart demonstrating significantly faster high-energy phosphate salvage, improved diastolic function, and pulse pressure recovery. The data attest to the beneficial effects of heat acclimation on cardiac mechanics of trained rats during normoperfusion and cardiac protection on ischemia and reperfusion. Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia and improved energy salvage on reperfusion contribute synergistically to this potent beneficial effect.

Acclimatization↗