Biomedical subjects

P Nicod

Publications and source records attributed to P Nicod.

At least 73 records · Page 4Linked to original sources

PubMed1995

[Hypoglycemia: diagnostic approach].

Hypoglycaemia can occur if the endogenous liver glucose output is lower than the glucose uptake in insulin-sensitive and insulin-insensitive tissues. The onset of hypoglycaemia induces the production of counterregulatory hormones such as glucagon, epinephrine, growth hormone and cortisol, and symptoms of neuroglycopenia. The correlation between biological hypoglycaemia and the symptoms associated with low blood sugar is particularly poor in diabetic patients and in patients with suspected postprandial hypoglycaemia. It is important to discriminate between fasting and postprandial hypoglycaemia. Idiopathic postprandial hypoglycaemia should be diagnosed clinically without further laboratory assessment, whereas the etiology of a fasting hypoglycaemia needs to be clarified further by laboratory testing, as it is potentially life-threatening.

Diabetes Mellitus↗

PubMed1995

[Malfunction of a mitral bioprosthesis, hemolysis and acute renal insufficiency].

Intravascular hemolysis is a rare complication following valvular replacement, particularly with bioprostheses. It is generally secondary to prosthetic malfunction and is the cause of anemia. We report a rare case of acute renal insufficiency and severe hemolysis caused by malfunction of a bioprosthesis in the mitral position.

Acute Kidney Injury↗

PubMed1995

Suppression of alcohol-induced hypertension by dexamethasone.

BACKGROUND: Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympatho-excitatory effects when administered centrally. METHODS: To determine whether alcohol evokes sympathetic activation and whether such activation is attenuated by the inhibition of CRH release, we measured blood pressure, heart rate, and sympathetic-nerve action potentials (using intraneural microelectrodes) in nine normal subjects before and during an intravenous infusion of alcohol (0.5 g per kilogram of body weight over a period of 45 minutes) and for 75 minutes after the infusion. Each subject received two infusions, one after the administration of dexamethasone (2 mg per day) and one after the administration of a placebo for 48 hours. RESULTS: The infusion of alcohol alone evoked a marked (P < 0.001) and progressive increase in the mean (+/- SD) rate of sympathetic discharge, from 16 +/- 3 bursts per minute at base line to 30 +/- 8 bursts per minute at the end of the two-hour period. This sympathetic activation was accompanied during the second hour by an increase in mean arterial pressure of 10 +/- 5 mm Hg (P < 0.001). After the administration of dexamethasone, the alcohol infusion had no detectable sympathetic effect. The dexamethasone-induced suppression of sympathetic activation was associated with a decrease in mean arterial pressure of 7 +/- 6 mm Hg (P < 0.001) during the alcohol infusion and with suppression of the pressor effect during the second hour. CONCLUSIONS: Alcohol induces pressor effects by sympathetic activation that appear to be centrally mediated. It is possible that these alcohol-induced hemodynamic and sympathetic actions could participate in triggering cardiovascular events.

Action Potentials↗

PubMed1995

[Clinical aspects and classification of unstable angina].

Unstable angina pectoris is a clinical syndrome with multiple underlying pathophysiologic mechanisms. This presentation is concerned with primary angina pectoris exclusively. In the majority of cases a rupture of an atherosclerotic plaque and an intracoronary thrombus are responsible for instable angina. The practitioner's role is to identify those patients who will develop complications with the aid of clinical parameters. Prinzmetal's angina is also instable, occurs at rest and leads to ST-segment elevation. It is most likely due to coronary spasm, developing in disease-free and atherosclerotic coronary segments alike. This variant of unstable angina is treated most successfully with calcium antagonists. The recognition of the responsible pathophysiologic mechanism permits adjustment of treatment of every patient taking into consideration the seriousness of his prognosis.

Angina Pectoris, Variant↗

PubMed1995

Immunolocalization of neuropeptide Y in human pancreatic endocrine tumors.

Neuropeptide Y (NPY) is a 36 amino acid peptide known to inhibit glucose-stimulated insulin secretion. NPY has recently been shown to be synthetized within rat islets of Langerhans and to be secreted in a differentiated rat insulin-secreting cell line, and as to this date the localization of NPY in human endocrine pancreas has not been reported. As NPY shares high amino acid sequence homology with peptide YY (PYY) and pancreatic polypeptide (PP), the polyclonal antibodies raised against these peptides often cross-react with each other. To demonstrate the presence of NPY in the human endocrine pancreas, we used a highly specific monoclonal antibody raised against NPY and another against its C-flanking peptide (CPON). We studied three cases of hyperplasia of Langerhans islets and 11 cases of endocrine tumors of the pancreas. NPY and CPON were detected in all three cases of hyperplasia. For the 11 pancreatic tumors, five and nine of the tumors were positive for the antibodies NPY and CPON, respectively. The two negative tumors for CPON immunoreactivity were differentiated insulinomas, which showed no evidence of other hormonal secretion. In normal Langerhans islet, NPY and CPON immunoreactivities were colocalized in glucagon-producing cells (alpha-cells) and in a few insulin-secreting cell (beta-cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Renin and angiotensin II receptor gene expression in kidneys of renal hypertensive rats.

The aim of this investigation was to examine the interrelation between renal mRNA levels of renin and angiotensin II receptor type 1 (AT1) in a renin-dependent form of experimental hypertension. Rats were studied 4 weeks after unilateral renal artery clipping. Mean blood pressure and plasma renin activity were significantly higher in the hypertensive rats (n = 10 206 +/- mm Hg and 72.4 +/- 20.9 ng/mL-1/h-1, respectively) than in sham-operated controls (n = 10, 136 +/- 3 mm Hg and 3.3 +/- 0.5 ng/mL-1/h, respectively). Northern blot analysis of polyA+ RNA obtained from the kidneys of renal hypertensive rats showed increased levels of renin mRNA in the clipped kidney, whereas a decrease was observed in the unclipped kidney. Plasma renin activity was directly correlated with renin mRNA expression of the poststenotic kidney (r = .94, P < .01). AT1 mRNA expression was lower in both kidneys of the hypertensive rats. This downregulation was specific for the AT1A subtype since the renal expression of the AT1B subtype remained normal in hypertensive rats. The downregulation of the renal AT1A receptor may be due to high circulating angiotensin II levels. This is supported by the significant inverse correlation (r = .71, P < .01) between plasma renin activity and AT1A mRNA expression measured in the clipped kidney of the hypertensive rats.

Animals↗

PubMed1995

Pancreatic-specific expression of the glucose transporter type 2 gene: identification of cis-elements and islet-specific trans-acting factors.

A defect in glucose sensing of the pancreatic beta-cells has been observed in several animal models of type II diabetes and has been correlated with a reduced gene expression of the glucose transporter type 2 (Glut2). In a transgenic mouse model, expression of Glut2 antisense RNA in pancreatic beta-cells has recently been shown to be associated with an impaired glucose-induced insulin secretion and the development of diabetes. To identify factors that may be involved in the specific decrease of Glut2 in the beta-cells of the diabetic animal, an attempt was made to localize the cis-elements and trans-acting factors involved in the control of Glut2 expression in the endocrine pancreas. It was demonstrated by transient transfection studies that only 338 base pairs (bp) of the murine Glut2 proximal promoter are needed for reporter gene expression in pancreatic islet-derived cell lines, whereas no activity was detected in nonpancreatic cells. Three cis-elements, GTI, GTII, and GTIII, have been identified by DNAse I footprinting and gel retardation experiments within these 338 bp. GTI and GTIII bind distinct but ubiquitously expressed trans-acting factors. On the other hand, nuclear proteins specifically expressed in pancreatic cell lines interact with GTII, and their relative abundance correlates with endogenous Glut2 expression. These GTII-binding factors correspond to nuclear proteins of 180 and 90 kilodaltons as defined by Southwestern analysis. The 180-kilodalton factor is present in pancreatic beta-cell lines but not in an alpha-cell line. Mutation of the GTI or GTIII cis-elements decreases transcriptional activity directed by the 338-bp promoter, whereas mutation of GTII increases gene transcription. Thus negative and positive regulatory sequences are identified within the proximal 338 bp of the GLUT2 promoter and may participate in the islet-specific expression of the gene by binding beta-cell specific trans-acting factors.

Animals↗

PubMed1995

Insulin-induced sympathetic activation and vasodilation in skeletal muscle. Effects of insulin resistance in lean subjects.

Insulin-induced stimulation of blood flow and sympathetic nerve activity in skeletal muscle tissue is impaired in obesity, but the underlying mechanism is unknown. To determine whether insulin resistance alters sympathetic and vasodilatory responses to euglycemic hyperinsulinemia, in eight healthy subjects we measured calf blood flow and muscle sympathetic nerve activity (MSNA) (n = 5) during insulin/glucose infusion (euglycemic hyperinsulinemic [6 pmol.kg-1.min-1] clamp) performed alone and performed during concomitant fat emulsion infusion, a maneuver designed to induce insulin resistance. The major new finding is that fat emulsion infusion, which attenuated insulin-induced stimulation of carbohydrate oxidation by 39 +/- 7% (P < 0.01), did not have any detectable effect on insulin-induced vasodilatory and sympathetic responses: at the end of the 2-h clamp, blood flow and MSNA had increased by 35 +/- 6% (P < 0.01) and 152 +/- 58% (P < 0.01), respectively, during insulin infusion alone and by 35 +/- 7% (P < 0.01) and 244 +/- 90% (P < 0.01), respectively, during insulin infusion superimposed on free fatty acid infusion. These observations in lean healthy subjects indicate that induction of resistance to the stimulatory effects of insulin on carbohydrate metabolism does not attenuate muscle blood flow and MSNA responses evoked by acute euglycemic hyperinsulinemia. These findings provide further evidence that hyperinsulinemia per se is the primary stimulus that triggers stimulation of muscle blood flow and MSNA during insulin/glucose infusion in humans and suggest that the impaired insulin-induced vasodilation in obese subjects is not related primarily to impaired stimulation of muscle carbohydrate metabolism.

Adult↗

PubMed1995

Metabolic effects of an increase of sympathetic activity in healthy humans.

OBJECTIVE: To determine the metabolic effects of catecholamines released at sympathetic nerves ending in the postabsorptive and postprandial states. DESIGN: Sympathetic activity was acutely increased by lower body negative pressure (LBNP; -15 mmHg) on two occasions in a group of eight healthy volunteers: (1) in the postabsorptive state; and (2) after glucose ingestion. MEASUREMENTS: Plasma norepinephrine concentrations were determined by HPLC and energy expenditure and substrate oxidation rates were assessed with indirect calorimetry. RESULTS: After glucose, LBNP increased plasma norepinephrine by 27% and lipid oxidation by 72% and decreased glucose oxidation by 14%. Energy expenditure was not altered. In the postabsorptive state, LBNP increased plasma norepinephrine by 34%, but had no significant effect on energy or substrate metabolism. CONCLUSIONS: In healthy humans, LBNP-induced activation of the sympathetic nervous system decreases glucose oxidation and increases lipid oxidation after oral glucose, but does not quantitatively affect energy expenditure.

Adult↗

PubMed1994

Characterization of the murine high Km glucose transporter GLUT2 gene and its transcriptional regulation by glucose in a differentiated insulin-secreting cell line.

In pancreatic beta-cells, the high Km glucose transporter GLUT2 catalyzes the first step in glucose-induced insulin secretion by glucose uptake. Expression of the transporter has been reported to be modulated by glucose either at the protein or mRNA levels. In this study we used the differentiated insulinoma cell line INS-1 which expresses high levels of GLUT2 and show that the expression of GLUT2 is regulated by glucose at the transcriptional level. By run-on transcription assays we showed that glucose induced GLUT2 gene transcription 3-4-fold in INS-1 cells which was paralleled by a 1.7-2.3-fold increase in cytoplasmic GLUT2 mRNA levels. To determine whether glucose regulatory sequences were present in the promoter region of GLUT2, we cloned and characterized a 1.4-kilobase region of mouse genomic DNA located 5' of the translation initiation site. By RNase protection assays and primer extension, we determined that multiple transcription initiation sites were present at positions -55, -64, and -115 from the first coding ATG and which were identified in liver, intestine, kidney, and beta-cells mRNAs. Plasmids were constructed with the mouse promoter region linked to the reporter gene chloramphenicol acetyltransferase (CAT), and transiently and stably transfected in the INS-1 cells. Glucose induced a concentration-dependent increase in CAT activity which reached a maximum of 3.6-fold at 20 mM glucose. Similar CAT constructs made of the human GLUT2 promoter region and the CAT gene displayed the same glucose-dependent increase in transcriptional activity when transfected into INS-1 cells. Comparison of the mouse and human promoter regions revealed sequence identity restricted to a few stretches of sequences which suggests that the glucose responsive element(s) may be conserved in these common sequences.

Animals↗

PubMed1994

Effects of adrenergic and cholinergic blockade on insulin-induced stimulation of calf blood flow in humans.

Euglycemic hyperinsulinemia stimulates both sympathetic nerve activity and blood flow to skeletal muscle, but the mechanism is unknown. Possible mechanisms that may stimulate muscle blood flow include neural, humoral, or metabolic effects of insulin. To determine whether such insulin-induced vasodilation is modulated by stimulation of adrenergic or cholinergic mechanisms, we obtained, in eight healthy lean subjects, plethysmographic measurements of calf blood flow during 3 h of hyperinsulinemic (1 mU.kg-1.min-1) euglycemic clamp performed alone or during concomitant beta-adrenergic (propranolol infusion), cholinergic (atropine infusion), or alpha-adrenergic (prazosin administration) blockade. Euglycemic hyperinsulinemia alone increased calf blood flow by 38 +/- 10% (means +/- SE) and decreased vascular resistance by 27 +/- 4% (P < 0.01). The principal new observation is that these insulin-induced vasodilatory responses were not attenuated by concomitant propranolol or atropine infusion, nor were they potentiated by prazosin administration. In conclusion, these findings provide evidence that during euglycemic hyperinsulinemia in lean healthy humans stimulation of muscle blood flow is not mediated primarily by beta-adrenergic or cholinergic mechanisms. Furthermore, alpha-adrenergic mechanisms do not markedly limit insulin-induced stimulation of muscle blood flow.

Adult↗

PubMed1994

Body fat and sympathetic nerve activity in healthy subjects.

BACKGROUND: Obesity is associated with an increased incidence of cardiovascular complications, but the underlying mechanism is unknown. In experimental animals, overfeeding is associated with sympathetic activation, and there is evidence that adrenergic mechanisms contribute to cardiovascular complications. METHODS AND RESULTS: We recorded resting postganglionic sympathetic nerve discharge (using intraneural microelectrodes) to skeletal muscle blood vessels in 37 healthy subjects covering a broad spectrum of percent body fat. To assess potential functional consequences of sympathetic nerve discharge, we simultaneously measured calf vascular resistance and energy expenditure. The resting rate of sympathetic nerve discharge to skeletal muscle was directly correlated with body mass index (r = .67, P < .0001) and percent body fat (r = .64, P < .0001). In addition to body fat, muscle sympathetic nerve activity was correlated with age (r = .40, P < .02), plasma insulin concentration (r = .34, P < .04), and plasma lactate concentration (r = .35, P < .04). Together, these four covariates accounted for 58% of the variance of muscle sympathetic nerve activity (P < .0001). The rate of sympathetic nerve discharge to calf blood vessels was directly correlated with calf vascular resistance (r = .40, P < .02) but did not predict energy expenditure (r = .22, P = .19). CONCLUSIONS: In healthy humans, body fat is a major determinant of the resting rate of muscle sympathetic nerve discharge. Overweight-associated sympathetic activation could represent one potential mechanism contributing to the increased incidence of cardiovascular complications in overweight subjects.

Adolescent↗

PubMed1994

Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans.

The sympathetic nervous system is an important regulatory mechanism of both metabolic and cardiovascular function, and altered sympathetic activity may play a role in the etiology and/or complications of obesity. In lean subjects, insulin evokes sympathetic activation and vasodilation in skeletal muscle. In obese subjects such vasodilation is impaired and, in turn, may contribute to insulin resistance. To examine the relationship between sympathetic and vasodilatory responses in skeletal muscle to hyperinsulinemia, we simultaneously measured muscle sympathetic nerve activity (MSNA) and calf blood flow at basal and during a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp in eight lean and eight obese subjects. The major findings of this study are twofold: obese subjects had a 2.2 times higher fasting rate of MSNA, and euglycemic hyperinsulinemia, which more than doubled MSNA and increased calf blood flow by roughly 30% in lean subjects, had only a minor vasodilatory and sympathoexcitatory effect in obese subjects. In contrast, two non-insulin-sympathetic stimuli evoked comparably large increases in MSNA in lean and obese subjects. We conclude that insulin resistance in obese subjects is associated with increased fasting MSNA and a specific impairment of sympathetic neural responsiveness to physiological hyperinsulinemia in skeletal muscle tissue.

Adult↗

PubMed1994

Nitric oxide release accounts for insulin's vascular effects in humans.

Insulin exerts effects on the vasculature that (a) may play a role in the regulation of blood pressure; and (b) by boosting its own delivery to target tissues, also have been proposed to play an integral part in its main action, the promotion of glucose disposal. To study the role of nitric oxide (NO) in the mediation of insulin's effects on the peripheral vasculature, NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived NO, was infused into the brachial arteries of healthy volunteers both before, and at the end of a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp. L-NMMA (but not norepinephrine, an NO-independent vasoconstrictor) caused larger reductions in forearm blood flow during hyperinsulinemia than at baseline. Moreover, L-NMMA prevented insulin-induced vasodilation throughout the clamp. Prevention of vasodilation by L-NMMA led to significant increases in arterial pressure during insulin/glucose infusion but did not alter glucose uptake. These findings indicate that insulin's vasodilatory effects are mediated by stimulation of NO release, and that they play a role in the regulation of arterial pressure during physiologic hyperinsulinemia. Abnormalities in insulin-induced NO release could contribute to altered vascular function and hypertension in insulin-resistant states.

Acetylcholine↗

PubMed1994

Mechanisms of dexamethasone-induced insulin resistance in healthy humans.

Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour. During the second hour, glucose uptake was normalized by means of hyperglycemia; glucose oxidation, however, remained suppressed by dexamethasone. Dexamethasone also abolished the insulin-mediated increase in calf blood flow. When acipimox was administered during the clamps to correct glucocorticoid-induced inhibition of glucose oxidation, dexamethasone decreased whole body glucose uptake and nonoxidative glucose disposal in the same proportion as when no acipimox was administered. However, glucose oxidation and insulin-mediated calf blood flow were normalized after acipimox. During the second hour, exogenous glucose infusion was matched to that used in the control clamp and normalized whole body glucose uptake. However, hyperglycemia developed, indicating insulin resistance. It is concluded that dexamethasone 1) decreases glucose oxidation independently of glucose transport; this inhibition is reversed by acipimox; and 2) decreases whole body glucose uptake independently of increased lipolysis, decreased glucose oxidation, or an altered muscle blood flow.

Adult↗

PubMed1993

Outcome after acute myocardial infarction in patients with prior coronary artery bypass surgery.

Little is known concerning the influence of remote prior coronary artery bypass grafting (CABG) on the outcome of patients with acute myocardial infarction (AMI). Therefore, this study evaluated 2,494 patients with AMI of whom 219 (8.8%) had a history of CABG a mean of 7.1 +/- 3.7 years before the index AMI. Compared with all other patients, those with a history of CABG had an increased prevalence of a history of prior AMI (153 [70%] vs 547 [24%]), congestive heart failure (48 [22%] vs 236 [10%]), and angina pectoris (165 [75%] vs 787 [35%]), all p < 0.001. There was no difference in age, but patients with prior CABG were more often men (192 [88%] vs 1,702 [75%], p < 0.001). During the hospitalization for AMI, patients with prior CABG had more recurrent ischemic pain (100 [46%] vs 732 [32%, p < 0.001]), and more frequently developed non-Q-wave AMI (72 [33%] vs 514 [23%], p < 0.01). In-hospital mortality did not differ among patients with or without prior CABG (15 [7%] vs 195 [9%]). At hospital discharge, more patients with prior CABG had complex ventricular ectopic activity on 24-hour ambulatory electrocardiographic monitoring (48 of 74 [65%] vs 327 of 797 [41%], p < 0.0001), and radionuclide ejection fraction < 0.45 (53 of 99 [54%] vs 430 of 1,024 [42%], p < 0.01). Among patients undergoing coronary angiography during the first 2 months, multivessel coronary artery disease was more prevalent among patients with prior CABG (78 of 107 [73%] vs 508 of 959 [53%], p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1993

[Laryngospasm: unusual manifestation of celiac disease].

Gluten-induced enteropathy or coeliac disease is a condition characterized by malabsorption and a variety of clinical manifestations. In adults, coeliac disease may be discovered while investigating iron-deficient anemia, bone pain or unexplained weight loss. We have recently diagnosed a case of gluten-induced enteropathy in an elderly woman whose symptoms were unusual. The patient had episodes of laryngospasm secondary to severe hypocalcemia and hypomagnesemia. The malabsorption syndrome was responsible for low levels of vitamin D, causing the electrolytic imbalance. Laryngospasm is a rare symptom of hypocalcemia and has not, to our knowledge, been described in the context of coeliac disease.

Aged↗

PubMed1993

Randomized placebo-controlled trial of amlodipine in vasospastic angina. Amlodipine Study 160 Group.

OBJECTIVES: This study was designed to assess the efficacy and safety of amlodipine, a long-acting calcium channel blocker, in patients with vasospastic angina. BACKGROUND: Previous studies have established the value of short-acting calcium channel blockers in the treatment of coronary spasm. METHODS: Fifty-two patients with well documented vasospastic angina were entered into the present study. After a single-blind placebo run-in period, patients were randomized (in a double-blind protocol) to receive either amlodipine (10 mg) or placebo every morning for 4 weeks. Twenty-four patients received amlodipine and 28 received placebo. All patients were given diaries in which to record both the frequency, severity, duration and circumstances of anginal episodes and their intake of sublingual nitroglycerin tablets. RESULTS: The rate of anginal episodes decreased significantly (p = 0.009) with amlodipine treatment compared with placebo and the intake of nitroglycerin tablets showed a similar trend. Peripheral edema was the only adverse event seen more frequently in amlodipine-treated patients. No patient was withdrawn from the double-blind phase of the study because of an adverse event. Patients who completed the double-blind phase as responders to amlodipine or as nonresponders to placebo were offered the option of receiving amlodipine in a long-term, open label extension phase. During the extension, the daily dose of amlodipine was adjusted to 5 or 15 mg if needed and the rate of both anginal episodes and nitroglycerin tablet consumption showed statistically significant decreases between baseline and final assessment. CONCLUSION: This study suggests that amlodipine given once daily is efficacious and safe in the treatment of vasospastic angina.

Adult↗