Use of the glucose clamp technique for confirmation of insulinoma autonomous hyperinsulinism.

The diagnosis of insulinoma on the basis of persistent hypoglycemia requires further confirmation. The insulin suppression test has been used to support this diagnosis prior to surgical intervention. In this study the euglycemic clamp technique was used to compare five control volunteers with four hypoglycemic patients with suspected insulinoma. Insulin was infused over successive two-hour periods at 2, 4, and 8 mU/kg/min. Plasma glucose levels were clamped at 80 mg/dL (4.4 mmol/L) using an artificial pancreas. High insulin levels were measured in all subjects, ranging from 225 +/- 30 microU/mL (1614 +/- 215 pmol/L) to 1018 +/- 239 microU/mL (7304 +/- 1714 pmol/L). Levels of C peptide fell to 0.1 ng/mL (0.028 nmol/L) in control subjects but remained at high levels in the patients. Insulinoma was confirmed on laparotomy in all four patients. In two patients tested after removal of the tumor the results were found to have returned to normal.

Short-term effect of red wine (consumed during meals) on insulin requirement and glucose tolerance in diabetic patients.

OBJECTIVE: To determine the effect of wine on insulin requirement or glucose tolerance. RESEARCH DESIGN AND METHODS: Five men with insulin-treated diabetes and 10 men with non-insulin-treated diabetes ate the same lunch with the same volume of either water or red wine (2 glasses). Insulin requirement was determined with an artificial pancreas (Biostator). Glucose tolerance was evaluated from the postprandial glycemic level. RESULTS: There was no significant difference in insulin requirement determined with an artificial pancreas in the insulin-treated patients after the two meals (31.5 +/- 4.21 U with water and 31.8 +/- 4.3 U with wine). Glucose tolerance in the non-insulin-treated patients was lower after the meal with wine. CONCLUSIONS: Moderate prandial wine consumption has no adverse effect on the glycemic control of diabetic patients. Thus, it appears unnecessary to proscribe the consumption of red wine in moderation with meals to diabetic patients. Wine contains tannins and phytates that can explain its action.

Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group.

OBJECTIVE: To study the predictive value of anti-Toxoplasma gondii antibody titres for the occurrence of toxoplasmic encephalitis (TE) in HIV-infected patients. METHODS: Data from the placebo arm of a trial of primary prophylaxis for TE (ANRS 005/ACTG 154) were analysed. Patients included had CD4+ cell counts < 200 x 10(6)/l and a positive Toxoplasma serology. Immunoglobulin (Ig) G and IgM Toxoplasma antibody titres at entry were retrospectively determined by enzyme-linked immunosorbent assay and agglutination on serum samples in a single laboratory. Incidence of TE was estimated by Kaplan-Meier method and a Cox model was used to study the predictive value of antibody titres, adjusted for other covariates. RESULTS: All 164 patients studied were positive for IgG antibodies and one had IgM antibodies. After a mean follow-up of 16 months, 31 cases of TE were documented. One-year incidence of TE was significantly higher in patients with IgG titres > or = 150 IU/ml (23.7%) than in patients with titres < 150 IU/ml (7.7%; relative risk, 3.1; P < 0.003). IgG titres remained significantly associated with the occurrence of TE (relative risk, 3.3; P < 0.005) in the Cox model. Predictive value of IgG titres did not differ according to baseline CD4+ cell counts. CONCLUSIONS: In patients with CD4+ cell counts < 200 x 10(6)/l, IgG anti-Toxoplasma antibody titre is a prognostic factor of occurrence of TE, with a higher risk for titres > or = 150 IU/ml. This finding should reinforce the recommendation of specific prophylaxis in these patients.

Effects of a low-protein, low-phosphorus diet on metabolic insulin clearance in patients with chronic renal failure.

The metabolic clearance rate (MCR) of insulin was studied in 17 nondiabetic patients with advanced chronic renal failure (creatinine 479 +/- 15 mumol/L, glomerular filtration rate 14.6 +/- 2.9 mL/min) before and after 3 mo of a low-protein, low-phosphorus diet (LPD) providing daily per kilogram 0.3 protein of vegetal origin and 3-5 mg inorganic phosphorus. The energy supply (146 kJ.kg-1 x d-1) was furnished mainly by carbohydrates. The diet was supplemented with a mixture of essential amino acids and keto-analogues. The MCR of insulin was determined by using the euglycemic clamp technique. Before the diet the MCR of insulin was low (450 +/- 127 mL.min-1 x m-2) but increased significantly at the third month (568.8 +/- 148 mL.min-1 x m-2), reaching values close to the MCR of control subjects (630 +/- 135 mL.min-1 x m-2). Identical results have been described during hemodialysis of anephric patients, leading us to hypothesize that an LPD reduces the production of dialyzable factors that interfere with peripheral insulin metabolism.

A low-protein diet improves insulin sensitivity of endogenous glucose production in predialytic uremic patients.

A low-protein, low-phosphorus diet (LPD) has been shown to improve insulin sensitivity in uremic patients; however, this improvement has not been studied at low physiologic concentrations of plasma insulin, and the metabolic pathways concerned with this improvement have not been located. We used the glucose clamp technique at a low (0.25 mU.kg-1.min-1) level of hyperinsulinemia associated with the infusion of D[6,6-2H2] glucose to assess the insulin sensitivity of endogenous glucose production (EGP). Eight nondialyzed uremic patients were studied before and after 3 mo on an LPD providing 0.3 g/kg protein, 5-7 mg P/kg, and 146 kJ/kg (67% of energy as carbohydrates and 30% as lipids) per day, supplemented with ketoanalog amino acids. Postabsorptive plasma glucose and insulin declined after 3 mo of the diet (plasma glucose: 5.0 +/- 0.1 mmol/L before compared with 4.7 +/- 0.1 mmol/L after the LPD, P < 0.05; plasma insulin: 82.4 +/- 20.7 pmol/L before compared with 48.8 +/- 6.0 pmol/L after, P < 0.05). Postabsorptive glucose turnover rates did not change with the diet (2.06 +/- 0.14 mg.kg-1.min-1 before compared with 2.11 +/- 0.17 mg.kg-1.min-1 after LPD; NS). The insulin metabolic clearance rate was enhanced after the diet, so a lower level of hyperinsulinemia was obtained during the clamp (168.8 +/- 28.1 pmol/L before compared with 115.2 +/- 14.7 pmol/L after; P < 0.05). However, EGP was more easily inhibited after the diet (0.90 +/- 0.31 mg.kg-1.min-1 before compared with 0.30 +/- 0.17 mg.kg-1.min-1 after; P < 0.05), providing evidence of an improved insulin sensitivity of this parameter. This beneficial influence takes place at a physiologic level of hyperinsulinemia, and it probably plays an important role in the better glucose tolerance that has been reported in uremic patients on an LPD. An abnormal insulin sensitivity of EGP may participate in the disturbances of glucose metabolism in chronic renal failure.

Influence of glycaemic normalisation by an artificial pancreas on phagocytic and bactericidal functions of granulocytes in insulin dependent diabetic patients.

Ten insulin dependent diabetic patients were maintained in normoglycaemia for 36 h with an artificial pancreas. Circulating polymorphonuclear leucocytes were extracted and incubated with staphylococcus before and after treatment; phagocytic and bactericidal activities were studied. Granulocytes from diabetic patients showed a decreased ability to absorb staphylococcus and a reduced capacity for intracellular destruction of bacteria. These two functions were improved after 36 h of normoglycaemia but were not corrected.

Teicoplanin: a well-tolerated and easily administered alternative to vancomycin for gram-positive infections in intensive care patients.

A prospective, randomized multicentre study was conducted in order to evaluate the potentially superior tolerability profile of teicoplanin plus netilmicin compared with vancomycin plus netilmicin in patients in ICUs. We considered that these glycopeptides have been shown to have comparable efficacy and that comparative tolerability is of paramount importance, particularly in severely ill patients. A total of 56 patients were enrolled into the study (36 males and 20 females). Twenty-four patients were included in the teicoplanin plus netilmicin group (15 males, 9 females: mean age 56.8 years). The mean simplified acute physiological score (SAPS) was 9.4 (range 4-20). Thirty-two patients were randomized to receive vancomycin plus netilmicin (21 males, 11 females; mean age 56.4 years). The mean SAPS was 9.3 (range 2-16). Septicaemia was the most common infection (14 cases in each group). Most infections were caused by Staphylococcus aureus or coagulase-negative staphylococci. The mean daily doses were: for teicoplanin, 457 mg (6.7 mg/kg); for vancomycin, 1678 mg (24.4 mg/kg); and for netilmicin 263.3 mg (3.9 mg/kg) in the teicoplanin group and 248 mg (3.8 mg/kg) in the vancomycin group. The trough levels of teicoplanin in the serum remained mostly between 7 and 10 mg/l, while more fluctuation was seen in patients receiving vancomycin. The mean trough levels of netilmicin in the serum were 1.2 (SD 0.9) mg/l in the teicoplanin group, compared with 1.7 (SD 1.4) mg/l in the vancomycin group (NS: p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Metformin improved insulin resistance in type I, insulin-dependent, diabetic patients.

The biguanides have been shown to reduce insulin requirements in type I (insulin-dependent) diabetic patients with an increase in insulin binding to insulin receptors. The aim of this was to measure the effect of metformin (850 mg/twice daily) on insulin sensitivity. Ten type I diabetic patients of normal weight received metformin or placebo in addition to their insulin therapy for seven days. On the last day of metformin or placebo treatment, tissue sensitivity was measured by the euglycemic hyperinsulinaemic clamp procedure using the artificial pancreas. An 18% improvement in glucose uptake was observed after metformin therapy (P less than 0.01). Metformin was therefore effective in improving the insulin action in type I diabetic patients, although its use in such circumstances requires consideration of several other factors.

Effects of red wine, tannic acid, or ethanol on glucose tolerance in non-insulin-dependent diabetic patients and on starch digestibility in vitro.

This study examines the effect of moderate intake of red wine, tannic acid, or ethanol during a meal in type 2 diabetic patients and the influence of tannic acid on the digestibility of starch by alpha-amylase. Thirty non-insulin-dependent diabetes mellitus (NIDDM) patients aged 53 +/- 6 years were studied (in vivo study) 10 of whom received red wine (200 mL), 10 tannic acid (150 mg), and 10 ethanol (16 g) with their midday meal (600 calories, 65 g carbohydrate, 20 g lipid, and 34 g protein). All patients were tested on two occasions (water or placebo v wine, alcohol, or tannic acid). The influence of tannic acid (0.25, 0.5, and 1 mg) on the digestibility of starch (100 mg) by alpha-amylase (100 U) was tested in vitro by sequential incubation at 37 degrees C (in vitro study). The maximum glucose excursion after lunch was 2.6 +/- 0.8 mmol/L at 90 minutes (T90) for water and 1.8 +/- 0.9 mmol/L at T90 for red wine taken with the meal. The values at T60 and T90 were significant (P < .01). Comparable results were obtained with tannic acid alone (nonalcoholic component of wine): the maximum glucose excursion after lunch was 2.76 +/- 0.9 mmol/L at T120 for placebo and 1.97 +/- 0.9 mmol/L at T90 for tannic acid (P < .01); no difference in glucose and insulin excursion was observed between water and ethanol. No interaction between tannic acid and starch was observed in the in vitro experiments, although after preincubation of alpha-amylase with tannic acid, digestion was slowed in a dose-dependent manner (6.1 +/- 1.1 minutes for 0.25 mg tannic acid and 13.1 +/- 1.59 minutes for 1 mg tannic acid). Drinking red wine with a meal did not increase blood glucose in NIDDM patients, and led to a slight decrease in some instances. The effect appeared to be mediated by the nonalcoholic compounds in wine such as tannic acid. Ethanol itself had no effect on plasma glucose or insulin levels.

Low protein and low phosphorus diet in patients with chronic renal failure: influence on glucose tolerance and tissue insulin sensitivity.

Ten patients with advanced renal failure (glomerular filtration rate 25 mL/min) were treated with a low phosphorus and low protein diet supplemented with ketoacid analogues. Before starting the diet and four months afterwards, a 50 g oral glucose tolerance test with a three step euglycemic insulin clamp was carried out. A dose-response curve of total body insulin sensitivity was plotted. By the fourth month, glucose tolerance had improved with significantly lower T0, T30, and T60 insulin levels. These results are attributed to the improvement in insulin action as demonstrated by the clamp technique. The dose-response curve had a distinctly higher plateau after dietary treatment, and the tissue sensitivity index to insulin (M/l ratio) was significantly improved. It is suggested that treatment of uremic patients with a low protein diet may reduce levels of a putative insulin inhibitor.

Effect of a ketoacid diet on glucose tolerance and tissue insulin sensitivity.

Effects of a low protein (0.3 g/kg/day) diet on glucose tolerance and tissue insulin sensitivity were studied in 25 non-diabetic and eight insulin-dependent diabetic uremic patients before and three months after dietary treatment. Carbohydrates accounted for 65% of the caloric intake in the first group and 57% in the second. In the first group, a 50 g oral glucose tolerance test showed that after three months blood glucose was significantly reduced at T60 (P less than 0.05) and serum insulin at T0, T30 (P less than 0.05) and T60 (P less than 0.02). Ten patients of the first group underwent an euglycemic, hyperinsulinemic clamp study; the tissue sensitivity to insulin index of all three clamp periods improved (P less than 0.01 for the first and second, P less than 0.02 for the third). Five patients in the second group underwent a euglycemic clamp study; glucose metabolism increased with each clamp period. Concomitantly, their daily insulin requirements decreased from 37.2 +/- 3.1 to 24.8 +/- 2.7 U/day (P less than 0.05). This conspicuous improvement observed in both groups might be related to a decrease in uremic toxin(s) derived from protein intake. Beneficial results on atherosclerosis and cardiovascular pathology may occur from the reduction of hyperinsulinism.

Study of the effect of metformin on platelet aggregation in insulin-dependent diabetics.

The role of metformin on platelet aggregation was studied in subjects affected by relatively well controlled type 1 diabetes. 1700 mg of metformin were added to their usual daily treatment; nothing else was changed. Patients were trained to monitor their own glycaemia and presence of degenerative retinopathy was proved. Before the administration of metformin and on day 21, the platelet induced by 1.25, 2.5 and 5 mumol of ADP and by collagen was studied. Fibrinogen, cholesterol, triglycerides, glycosylated haemoglobin and mean blood glucose levels did not show any significant modification after treatment but the maximum aggregation induced by ADP was significantly decreased; the inhibition of aggregation was particularly sensitive for low doses of ADP. No significant correlation was found between the variations in metabolism data and the reduction of the amplitude of platelet aggregation. Metformin, added to the usual treatment undergone by a diabetic treated with insulin, seems to affect platelet aggregation independently of other metabolic factors.

Echocardiographic study of left ventricular function in type 1 diabetes mellitus: hypersensitivity of beta-adrenergic stimulation.

Systolic left ventricular function was investigated by echocardiography in 23 young, type 1 diabetics and 11 control subjects. A stimulation by isoproterenol was performed in order to study beta-adrenergic cardiac responsiveness. M-mode recordings were digitized and analyzed by computer. Systolic parameters such as left ventricular fractional shortening and mean velocity of circumferential shortening were not different, but maximal velocity of shortening was increased both at rest (P less than 0.01) and with isoproterenol (P less than 0.05) in the diabetics. An abnormal systolic anterior motion of the mitral valve was found during administration of isoproterenol in 65% of the diabetics and in only one control. These findings are suggestive of a hyperkinetic state, associated with a poor metabolic control (high value of HbA1), together with adrenergic hypersensitivity in type 1 diabetes mellitus.

Study of insulin metabolism in hyperthyroid patients.

Hyperthyroidism is associated with degradation of carbohydrate metabolism. The insulin metabolism in 12 hyperthyroid patients is compared with 10 control subjects. The patients were connected to an artificial beta cell (Biostator GCIIS Miles) for two hours of insulin infusion (40 mU/m2/mn) while glycemia was maintained at its basal level by a modulated glucose infusion. Blood samples were taken, every 15 minutes for insulin and C peptide dosage. In control subjects the insulin steady state level was 93.3 +/- 5 microU/ml whereas this ranged from 42 +/- 3.4 microU/ml to 68 +/- 3.9 microU/ml in hyperthyroid patients. After treatment the insulin level was not quite normal, and ranged from 52 +/- 4.8 microU/ml to 82.2 +/- 9 microU/ml. A glucose intake not corresponding to the same insulin steady state is not therefore to be interpreted. Here there is no evidence of a correlation between the percentage decrease in the insulin test level and the thyroid hormone levels. An impairment of insulin metabolism is suggested in hyperthyroid patients, which might contribute to the decrease in carbohydrate tolerance.

Diagnostic ERCP in the era of laparoscopic surgery.

BACKGROUND/AIMS: The purpose of this paper is to reassess the place and risks of ERCP in a diagnostic view. METHODS: Analysis of 196 non-operative ERCP performed in 196 patients aged 57 +/- 20 yrs. ERCP was performed for: unexplained cholestasis = 98; non tumoral pancreatic diseases = 43; suspected neoplasm of the pancreatic/biliary tract = 13; cholangitis = 12; unexplained abdominal pain = 30. Precut papillotomy was performed in 40 cases (20.4%). 10.7% were cirrhotics; 3.1% were gastrectomized. 164/196 received peri-operative broad-spectrum antibiotics. RESULTS: 108 had normal ERCP (group I); 74 had abnormal ERCP (group II); 12 had undetermined diagnosis after ERCP (group III). Strictly ERCP-induced mortality was nil; 2 patients died a few days after ERCP from: hemorrhage after transhepatic drainage (1); continuing severe cholangitis after failed CBD cannulation (1). Morbidity was: acute pancreatitis = 6 (3%) and fever = 4 (2%). No complication followed precut papillotomy. The 6 pancreatitis recovered within 48 h to 5 days. Fevers alleviated with antibiotics within 12 to 48 h. Pancreatitis occurred in 5/6 after normal ERCP; fevers followed pathologic ERCP in 3/4 (NS). The high rate of precuts in this series did not increase morbidity. CONCLUSION: ERCP-related morbidity was 5.1 % and ERCP accurately diagnosed or unequivocally eliminated biliary-pancreatic disease in 92.9%. These results suggest that ERCP remains a useful and safe diagnostic tool.

Pharmacokinetics of amoxycillin according to administration schedule.

Thirty subjects, free of any heart, kidney or liver disease, were given the same dosage of amoxycillin--100 mg/kg/24 hr. The first ten were given the drug in three equal doses at 8-hourly intervals, a further ten in four doses at 6-hourly intervals, and the last ten in eight doses at 3-hourly intervals. The final administration schedule resulted in much higher and more regular serum levels of amoxycillin than the other two, suitable for the treatment of severe infectious conditions, and has the advantage of avoiding prolonged antibiotic infusions which are a source of venous complications in the patient. The first results obtained clinically, which will be published in a further paper, seem favourable.

[A new hereditary cause of portal vein thrombosis: the abnormal resistance to activated protein C by the Arg 506-->Gln mutation of the gene of factor V]. / Une nouvelle cause héréditaire de thrombose portale: la résistance anormale à la protéine C activée par mutation Arg506-->Gln du gène du facteur V.

We report 2 cases of portal vein thrombosis associated with a single point mutation in the factor V gene that replaces arginine in residue 506 with glutamine. This mutation induces abnormal resistance to anticoagulant activity of activated protein C and increases the risk of deep vein thrombosis. Both patients had a personal and familial history of deep vein thrombosis. Intraabdominal neoplasia or infection, myeloproliferative disorder, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria and coagulation inhibitor deficiency (antithrombin, proteins C and S) were excluded by exhaustive investigation. However, an abnormal resistance to activated protein C was found, and DNA analysis showed the factor V Arg506 to Gln mutation in both cases. Anticoagulant treatment was begun. A study of family history made in one case, showed the same genetic disease in one of the relatives. Resistance to activated protein C with factor V gene mutation should be investigated in patients with portal vein thrombosis. A study of family history, and anticoagulant treatment are justified for symptomatic patients.

[Prospective comparison of ultrasound endoscopy and computed tomography in the assessment of locoregional invasiveness of malignant ampullar and pancreatic tumors verified surgically]. / Comparaison prospective de l'échoendoscopie et de la tomodensitométrie dans le bilan d'extension loco-régionale de tumeurs malignes ampullaires et pancréatiques vérifiées chirurgicalement.

OBJECTIVE: To compare, in a prospective study, results of endoscopic ultrasonography and computed tomography in staging of pancreatic and ampullary carcinoma tumours, assessed surgically. METHOD: From January 1990 to May 1993, 37 patients with pancreatic tumours had per-operative endoscopic ultrasonography and computed tomography. All patients underwent surgery and surgical and histological staging were performed. RESULTS: All the tumours were visualized by endoscopic ultrasonography, and 92% were correctly localized; 63% of the tumours were visualized by computed tomography. In lymph node involvement diagnosis (23 patients), endoscopic ultrasonography. In major portal vessel involvement diagnosis (14 patients), endoscopic ultrasonography sensitivity and specificity were respectively 71.4% and 95.65%, and 21.4% and 100% for computed tomography. In a vessel-by-vessel analysis, endoscopic ultrasonography was superior to computed tomography for veinous involvement diagnosis (sensitivity: 68.4% vs 26.3%), and the results were similar for arterial involvement diagnosis (sensitivity: 55.5% vs 66.6%). CONCLUSION: Endoscopic ultrasonography is more accurate than computed tomography in detection of metastatic lymph nodes and portal involvement, and their results are similar in detection of arterial involvement.

[Hepatic manifestations of psittacosis]. / Les manifestations hépatiques de la psittacose.

A moderate increase in transaminases and alkaline phosphatase serum concentrations was observed in 14 of 32 patients with psittacosis (antibodies anti-Chlamydia psittaci greater than or equal to 1/40 with the complement fixation test). Clinical manifestations were present in 4 patients (hepatomegaly in 4 cases; jaundice in one case). In one patient, histological examination of a liver specimen showed granuloma. In 13 patients treated with tetracycline or macrolides, the outcome was favorable. One patient recovered spontaneously. In comparison with the group of 18 patients without hepatic involvement, there was no difference pertaining to epidemiological, clinical, or serological findings. Equally, there was no difference in the course of the disease.

["Dysphagia lusoria". Physiopathological discussion apropos of a clinical case]. / "Dysphagia lusoria". Discussion physio-pathologique à propos d'un cas clinique.

We report the observation of a patient suffering from dysphagia lusoria, a dysphagia caused by an anomalous form of the right subclavian artery. The diagnosis was confirmed by aortic arch angiography and cine-oesophagogram. Oesophageal manometric study revealed segmental hypoperistalsis and anti-peristalsis. Dysphagia disappeared with cisapride. This observation suggests that dysphagia lusoria is caused by oesophageal motility disorders and not by vascular compression.