Biomedical subjects

Jacques Rahier

Publications and source records attributed to Jacques Rahier.

26 records · Page 2Linked to original sources

PubMed2002

Limited lamivudine and long-term hepatitis B immunoglobulin immunoprophylaxis for prevention of hepatitis B recurrence after liver transplantation.

BACKGROUND: No consensus exists concerning dosage and duration of prophylactic hepatitis B immunoglobulin and lamivudine for prevention of hepatitis B recurrence after liver transplantation (LT). METHODS: Lamivudine was discontinued 12 months after LT, maintaining hepatitis B immunoglobulin prophylaxis in eight patients who received lamivudine treatment before LT. RESULTS: At LT, six patients were serum hepatitis B virus (HBV)-DNA negative, whereas two patients had low serum HBV-DNA levels. Hepatitis B surface (HBs) antigen and hepatitis B core antigen stained positively by immunohistochemistry in all hepatectomy specimens. All patients remained recurrence free during the 12 months on combination therapy with normal liver histological examination and negative HBs and HB core staining on biopsy specimens. No relapse occurred after lamivudine withdrawal during a median follow-up of 17.5 months (normal transaminases, negative serum HBs antigen, and HBV-DNA). CONCLUSIONS: Discontinuation of lamivudine 12 months after LT is feasible and safe even in patients with ongoing low viral replication at LT, providing adequate prophylaxis with hepatitis B immunoglobulins.

Adult↗

PubMed2002

Facial appearance in persistent hyperinsulinemic hypoglycemia.

Persistent hyperinsulinism is the most common cause of recurrent hypoglycemia in infancy because of inappropriate oversecretion of insulin by the pancreas. Pancreatic lesions can be either focal or diffuse, and they have distinct molecular bases. We have studied the facial features in 17 unrelated patients presenting with neonatal (n = 8) or infancy-onset (n = 9) hyperinsulinism. Hyperinsulinism was related to focal adenomatous hyperplasia (n = 7), diffuse hyperinsulinism (n = 5), non-operated hyperinsulinism (n = 2), and hyperinsulinism with hyperammonemia (n = 3). SUR1 or Kir6.2 mutations were found in six of seven focal adenomatous hyperplasia and three of five diffuse hyperinsulinism. A loss of the maternal allele from chromosome 11p15 in the lesion was found in all focal adenomatous hyperplasia. GLUD1 mutations were found in all patients with hyperammonemia. Large birth weight (mean > 3,800 g) was consistently observed (11/17) but protruding tongue, exomphalos, or visceromegaly were never noted and Wiedemann-Beckwith syndrome could always be ruled out. All patients presented with high forehead, small nasal tip, and short columella giving the impression that the nose is large and bulbous, smooth philtrum, and thin upper lip. A square appearance to the face was more obvious in younger patients. These specific facial features, observed in patients with hyperinsulinism of various molecular mechanisms, could be the consequence of fetal intoxication by insulin. However, to date, facial anomalies have not been noted in infants of diabetic mothers and inversely, malformations that are commonly reported in infants of diabetic mothers were not present in our hyperinsulinemic patients.

ATP-Binding Cassette Transporters↗

PubMed2002

Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases.

UNLABELLED: Hyperinsulinism is a heterogeneous disorder characterised by severe hypoglycaemia due to an inappropriate oversecretion of insulin. In a personal series of 175 patients investigated for hyperinsulinaemic hypoglycaemia over the last 20 years, we review clinical presentations, molecular studies and therapeutic management of hyperinsulinism. There were 98 neonatal-onset patients, including 86 permanent hyperinsulinism and 12 transient forms, 68 with infancy-onset and nine with childhood-onset. Hyperammonaemia was found in 12 out of 69 patients tested, 4 neonates and 8 infants. Neonates were clinically more severely affected than infants. Diagnosis of infancy-onset hyperinsulinism was often delayed because of less profound hypoglycaemia and better tolerance to hypoglycaemia. Neonates required higher rates of i.v. glucose than infants to maintain normal plasma glucose levels (16 mg/kg per min versus 12 mg/kg per min). Only 16% of neonates were diazoxide-sensitive compared to 66% of the infants. Neonates with hyperammonaemia or transient hyperinsulinism were diazoxide-sensitive. Most neonates were pancreatectomised whereas 65% of the infants were treated medically. Among surgically-treated patients, 47% had a focal adenomatous hyperplasia (31 neonates and 13 infants) and 53% a diffuse form of hyperinsulinism (39 neonates and 11 infants). Diazoxide-responsiveness in the focal and diffuse forms did not differ in both neonates and infants; it depended only upon the age of onset of hypoglycaemia. One or two mutations, SUR1 or KIR6.2, were found in 41 of 73 neonates who were investigated and in 13/38 infants using polymerase chain reaction-single strand conformational polymorphism analysis of both genes. Almost all patients with SUR1 (38/41) or KIR6.2 (5/7) mutations were resistant to diazoxide. Ten patients with hyperinsulinism-hyperammonaemia syndrome had a mutation in the glutamate dehydrogenase gene (three neonates and seven infants) after reverse transcriptase-polymerase chain reaction and sequence analysis of cDNA. No mutation was found by polymerase chain reaction-single strand conformational polymorphism in the glucokinase gene. Eight of nine patients with childhood onset hyperinsulinism were treated surgically and histological examination confirmed an adenoma in each case. CONCLUSION: the clinical severity of hyperinsulinism varies mainly with age at onset of hypoglycaemia. The heterogeneity of hyperinsulinism has major consequences in terms of therapeutic outcome and genetic counselling.

Age of Onset↗

PubMed2002

Delayed and prolonged cholestatic hepatitis with ductopenia after long-term ciprofloxacin therapy for Crohn's disease.

Ciprofloxacin, a fluorinated quinolone, is a powerful antibiotic widely used for its broad spectrum of activity in ambulatory and long-term care setting. Until now, ciprofloxacin administration has been associated with a few cases of acute, sometimes cholestatic jaundice or fulminant hepatic failure believed mainly related to idiosyncratic hypersensitivity. We report a case of delayed and prolonged cholestatic hepatitis with ductopenia occurring after 6 months of treatment in a patient with Crohn's disease. This observation suggests the potential for the drug to induce long-term likely dose-related severe hepatotoxicity.

Anti-Infective Agents↗

PubMed2002

Expression of cholecystokinin in the duodenum of patients with coeliac disease: respective role of atrophy and lymphocytic infiltration.

Cholecystokinin (CCK) release after a standard test meal is decreased in coeliac patients. The aim of the study was to determine the origin of the CCK deficiency and the relationship between the distinctive types of mucosal lesions observed in coeliac disease and the number of duodenal CCK cells and their peptide and mRNA content. Duodenal biopsies were obtained in ten controls and nineteen coeliac patients [seven with atrophic mucosa, six with increased numbers of intraepithelial lymphocytes (IELs) and six with fully normalized mucosa]. Immunocytochemistry was performed with a CCK C-terminal-specific polyclonal antiserum. The CCK cells were counted and related to the epithelial area using a semi-automated image analyser. CCK content in mucosal extracts was determined by radioimmunoassay. mRNA was measured with a semi-quantitative reverse transcriptase-PCR method using specific CCK and ribosomal protein L19 (RPL19) primers. CCK tissue concentration and CCK mRNA were significantly reduced in patients with atrophic mucosa [12.2 (range 6.9-17.5) pmol/g; CCK/RPL19 ratio 0.64 (0.30-0.99)] compared with patients with normal mucosa [40.5 (30.4-50.7) pmol/g; CCK/RPL19 ratio 1.40 (0.41-2.40)] or controls [42.7 (18.2-67.2) pmol/g; CCK/RPL19 ratio 1.35 (1.09-1.62)]. A similar decrease was observed in patients with an excess of IELs, 13.9 (3.8-31.8) pmol/g and 0.86 (0.57-1.15) pmol/g respectively. The number of CCK cells was, however, similar in all groups. Duodenal CCK concentration and mRNA are decreased not only in the mucosa presenting atrophic changes but also when disease activity is limited to infiltration by IELs. Reduced expression of the CCK gene could therefore be related to suppressive factors induced by the inflammatory infiltrate.

Adult↗

PubMed2002

BPDZ 154 activates adenosine 5'-triphosphate-sensitive potassium channels: in vitro studies using rodent insulin-secreting cells and islets isolated from patients with hyperinsulinism.

A novel ATP-sensitive potassium channel (K(ATP)) channel agonist, BPDZ 154 (6,7-dichloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide), was synthesized, and its effects on insulin-secreting cells were evaluated using electrophysiology, (86)Rb(+) and (45)Ca(2+) efflux, and RIA determinations of insulin secretion. BPDZ 154, an analog of diazoxide, inhibited both glucose-induced insulin secretion from isolated perifused islets and the secretion of insulin induced by glucose and tolbutamide. These effects were mediated by the activation of ATP-sensitive potassium channels because BPDZ 154 induced a concentration-dependent increase in channel activity that was inhibited by the sulfonylurea tolbutamide and the imidazoline efaroxan. In beta-cells isolated from patients with either nontypical hyperinsulinism (preserved K(ATP) channel function) or from the control areas of the pancreas of patients with focal hyperinsulinism, BPDZ 154 activated K(ATP) channels and was found to be more effective and less readily reversible than diazoxide. By contrast, it was not possible to activate K(ATP) channels by either diazoxide or BPDZ 154 in beta-cells from patients with hyperinsulinism as a consequence of defects in K(ATP) channel function. In beta-cells isolated from a patient with pancreatic insulinoma, K(ATP) channels were readily recorded and modulated by BPDZ 154. These data suggest that BPDZ 154 or BPDZ 154-like compounds may have therapeutic potential in the treatment of certain forms of hyperinsulinism.

Adenosine Triphosphate↗

PubMed2002

SERCA3 ablation does not impair insulin secretion but suggests distinct roles of different sarcoendoplasmic reticulum Ca(2+) pumps for Ca(2+) homeostasis in pancreatic beta-cells.

Two sarcoendoplasmic reticulum Ca(2+)-ATPases, SERCA3 and SERCA2b, are expressed in pancreatic islets. Immunocytochemistry showed that SERCA3 is restricted to beta-cells in the mouse pancreas. Control and SERCA3-deficient mice were used to evaluate the role of SERCA3 in beta-cell cytosolic-free Ca(2+) concentration ([Ca(2+)](c)) regulation, insulin secretion, and glucose homeostasis. Basal [Ca(2+)](c) was not increased by SERCA3 ablation. Stimulation with glucose induced a transient drop in basal [Ca(2+)](c) that was suppressed by inhibition of all SERCAs with thapsigargin (TG) but unaffected by selective SERCA3 ablation. Ca(2+) mobilization by acetylcholine was normal in SERCA3-deficient beta-cells. In contrast, [Ca(2+)](c) oscillations resulting from intermittent glucose-stimulated Ca(2+) influx and [Ca(2+)](c) transients induced by pulses of high K(+) were similarly affected by SERCA3 ablation or TG pretreatment of control islets; their amplitude was increased and their slow descending phase suppressed. This suggests that, during the decay of each oscillation, the endoplasmic reticulum releases Ca(2+) that was pumped by SERCA3 during the upstroke phase. SERCA3 ablation increased the insulin response of islets to 15 mmol/l glucose. However, basal and postprandial plasma glucose and insulin concentrations in SERCA3-deficient mice were normal. In conclusion, SERCA2b, but not SERCA3, is involved in basal [Ca(2+)](c) regulation in beta-cells. SERCA3 becomes operative when [Ca(2+)](c) rises and is required for normal [Ca(2+)](c) oscillations in response to glucose. However, a lack of SERCA3 is insufficient in itself to alter glucose homeostasis or impair insulin secretion in mice.

Animals↗

PubMed2002

[Persistent hyperinsulinemic hypoglycemia of infancy: the pathologist's experience].

Persistent hyperinsulinemic hypoglycemia of Infancy (PHHI) is characterized by episodes of severe hypoglycemia exposing the child to serious neurological sequelae. The morphologic pancreatic anomalies observed consist in either a focal lesion which can be totally cured by a selective surgical resection, or a diffuse and poorly understood lesion of pancreatic tissue, which may appear at first glance to be both macroscopically and microscopically normal, the treatment of which, requires a near-total pancreatectomy. The studies presented concentrate on several pathogenic hypotheses of this latter form of PHHI. We first demonstrate that nesidioblastosis, long considered as the original lesion for the diffuse form of hyperinsulinism, does indeed exist although it is not specific to this disease and does not correspond to a permanent proliferation of endocrine cells. We then dismiss the hypothesis of an enhanced B cell mass, as the volume density of B cells is not systematically increased in hyperinsulinemic children compared to controls. The third hypothesis looking to a decreased D cell mass has to be approached with circumspection as the difference in volume density of somatostatin cells, which tends to be slightly lower in hypoglycemic children, is small and inconsistent. The fourth hypothesis concerns an intrinsic functional lesion of the B cells, and is supported by an increased quantity of proinsulin detected in the Golgi area as well as by the observation of voluminous nuclei and a particularly abundant cytoplasm in certain B cells. These histological anomalies are detected on per-operative frozen sections and guide the surgical treatment.

Humans↗