Necrotizing fasciitis of the lower limb after venous surgery: cases studies and a review of the literature.

We report 2 cases of necrotizing fasciitis following stripping of the long saphenous vein and phlebectomy of varicose collateral vessels. The first one concerns a 42-year-old man who presented with a left thigh postoperative infection, evolving despite oral antibiotic therapy. Urgent surgical exploration proved an extensive necrosis consistent with necrotizing fasciitis. Wide excision of the necrotic tissue was performed. Under intravenous antibiotic therapy, local wound care and hyperbaric oxygen therapy, the patient's condition improved. The second case concerns a 60-year-old man with cardio-vascular disease and diabetes. He was transferred in our institution 7 days after surgery for an infection in the right thigh and septic shock. Immediate surgical exploration showed extensive necrotizing fasciitis of the thigh, popliteal fossa and latero-posterior compartments of the leg. Muscle necrosis of the right leg was also observed. A right supra-condylar amputation was performed. The patient improved under antibiotherapy and hyperbaric oxygen therapy.

Quercetin potentiates insulin secretion and protects INS-1 pancreatic ß-cells against oxidative damage via the ERK1/2 pathway.

BACKGROUND AND PURPOSE: Quercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic ß-cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin-secreting ß-cells. Using the INS-1 ß-cell line, the effects of quercetin were determined on glucose- or glibenclamide-induced insulin secretion and on ß-cell dysfunctions induced by hydrogen peroxide (H(2)O(2)). These effects were analysed along with the activation of the extracellular signal-regulated kinase (ERK)1/2 pathway. N-acetyl-L-cysteine (NAC) and resveratrol, two antioxidants also known to exhibit some anti-diabetic properties, were used for comparison. EXPERIMENTAL APPROACH: Insulin release was quantified by the homogeneous time resolved fluorescence method and ERK1/2 activation tested by Western blot experiments. Cell viability was estimated by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) colorimetric assay. KEY RESULTS Quercetin (20 µmol·L(-1)) potentiated both glucose (8.3 mmol·L(-1))- and glibenclamide (0.01 µmol·L(-1))-induced insulin secretion and ERK1/2 phosphorylation. The ERK1/2 (but not the protein kinase A) signalling pathway played a crucial role in the potentiation of glucose-induced insulin secretion by quercetin. In addition, quercetin (20 µmol·L(-1)), protected ß-cell function and viability against oxidative damage induced by 50 µmol·L(-1) H(2)O(2) and induced a major phosphorylation of ERK1/2. In the same conditions, resveratrol or NAC were ineffective. CONCLUSION AND IMPLICATIONS: Quercetin potentiated glucose and glibenclamide-induced insulin secretion and protected ß-cells against oxidative damage. Our study suggested that ERK1/2 played a major role in those effects. The potential of quercetin in preventing ß-cell dysfunction associated with diabetes deserves further investigation.

Spontaneous cystic artery rupture: a rare cause of haemoperitoneum.

We report the case of a 74-year-old man who presented an acute haemoperitoneum further to the rupture of the cystic artery. The bleeding was successfully controlled using embolization. This procedure was complicated by ischaemic necrosis and perforation of the gall-bladder requiring laparoscopic cholecystectomy. Spontaneous rupture of intra-abdominal arteries is a rare event. This usually occurs in abnormal arteries, presenting pseudo-aneurysm or, weakened by arterial hypertension, diabetes or corticotherapy. In the case of a cystic artery rupture, embolization can be safely done as long as the arterial anastomotic network with hepatic parenchyma is sufficient to supply the gall-bladder.

[Iron deficiency anaemia, pancreatitis and epigastric mass in a young female: a rare presentation of a large gastric trichobezoar]. / Anémie ferriprive, pancréatite et masse epigastrique chez une jeune patiente: une présentation clinique rare d'un volumineux trichobézoard gastrique.

We report the case of a 15-year old girl presenting with a gastric fullness sensation. The biological examination showed iron deficiency anaemia and elevation of the pancreatic enzymes. At endoscopy, a huge trichobezoar is found in the stomach. The endoscopic removal is impossible due to the compacity of the mass. Surgical resection is therefore performed. The postoperative course is uneventful and the biologic anomalies are rapidly corrected. A throughout anamnesis revealed a trichotillomania with trichophagia, this behavioural trouble found its origin in a familial conflict.

In utero urinary bladder rupture: a case report.

We report a case of foetal urinary bladder rupture due to posterior urethral valves. A megacystis was diagnosed in a male foetus during routine second trimester ultrasound examination. The diagnosis of bladder rupture was made as, one week later, the bladder became undetectable with the appearance of ascites. During the follow-up, no oligohydramnios developed and intercurrent ascites resolved spontaneously. There are three described mechanisms releasing bladder hyperpressure: bladder diverticles, unilateral vesicoureteral reflux and bladder rupture. In this case, another mechanism might be involved: a patent urachus. The urethral valves were resected and no other surgical treatment was needed. The renal function remained normal. No long-term vesical follow-up of this pathology is available in the literature.

Perineal lipoma in a newborn boy--a case report.

We report the case of a newborn presenting with a pediculated mass arising from the anal margin. Antenatal sonogram and magnetic resonance imaging were unable to diagnose the precise nature of the lesion. Sacrococcygeal teratoma, an enterogenous cyst, a polyp, a prolapse or other perineal tumors were all proposed as possible entities. At birth, no other anatomic anomaly than this homogenous 2 cm para-anal lesion was seen. Excision of the mass was performed under general anesthesia. The postoperative histological exam showed mature fat cells. Reviewing the literature, there have been few previously reported cases of congenital perineal lipoma. It is a rare, benign and easy-to-treat condition that can be evocated by morphological sonography or magnetic resonance imaging (MRI).

Laparoscopic revision for failed anti-reflux surgery. Preliminary results.

BACKGROUND/AIMS: Surgical treatment of gastroesophageal reflux disease has become common practice. These operations are known to fail in about 10%, the need for re-intervention approximates 5%. Re-fundoplications are feasible laparoscopically but are technically demanding. METHODOLOGY: For the present paper, we reviewed retrospectively the 10 patients that, in our practice, needed a re-intervention for failure of a prior fundoplication. The causes were: narrowed passage at wrap level (n=4), intra-thoracic wrap migration (n=3), wrap disruption (n=2) and gastric volvulus (n=1). RESULTS: All 10 patients underwent a re-operation consisting of a confection of a new 360 degrees wrap. All interventions were completed laparoscopically and no major complication occurred. The results of these revised fundoplications were satisfying with complete resolution of reflux and/or dysphagia in all patients but one. This latter patient still needed anti-acid medication for an unexplained persistent reflux. CONCLUSIONS: In our experience, laparoscopic correction of failed fundoplications is technically feasible and associated with low rate of complications and high success rate.

Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine.

Glicentin (GLIC) and oxyntomodulin (OXM or GLIC 33-69) are gut hormones which regulate digestion. They are known to reduce digestive secretions and to delay gastric emptying. Their biological activities on intestinal motility are still unknown. The effect of a systemic GLIC or OXM increase was investigated in rats on the food intake, the postprandial myoelectrical activity of small intestine and the orocaecal transit. An OXM or GLIC i.v. infusion was applied during the 5 min preceding food onset and during the first 15 min of food intake. This determined a three- to fourfold increase of the preprandial OXM-GLIC level. The OXM or GLIC plasma increase did not modify food intake. OXM infusion slowed down gastric emptying when the stomach contained 3/4 of the ingested food (before T 3 h). The quantity of food delivered in jejunum was subsequently smaller (P < 0.05). In the small intestine, the duration of postprandial myoelectrical activity (50-60 min g(-1) of ingested food) was reduced by 70% (P < 0.001) on duodenum or jejunum and by 54% (P < 0.01) on ileum in OXM-treated rats. An interdigestive motility profile was settled and an acceleration of both gastric emptying and transit rate was thereafter evidenced (after T 3 h). GLIC also reduced the duration of the postprandial myoelectrical activity on duodenum and jejunum (65 and 63% respectively, P < 0.05), but was not as efficient as OXM on ileum. In pathological states such as acute adult gastroenteritis, OXM and GLIC exhibit a two- to fivefold increase in their plasma concentrations. The present findings suggest that OXM and GLIC could, in that disease, contribute to exclude pathogens, due to their joined action on gut motility.

[Polymyositis induced or associated with lipid-lowering drugs: five cases]. / Polymyosites induites ou associées aux traitements hypolipémiants? A propos de cinq cas.

PURPOSE: Rhabdomyolysis and myositis are rare, dose-related complications of statins and fenofibrates. The outcome is favorable as a rule with rapid regression after stopping the responsible drug. Recently, various auto-immune disease with evidence of hypersensitivity to HMG-CoA reductase inhibitors or fibrates drugs have been reported. Less than ten cases of dermatomyositis and polymyositis due to cholesterol-lowering drugs (CLD) have been previously reported. Five more cases polymyositis associated with CLD are reported. METHODS: Symptoms were compatible with diagnosis of polymyositis according to Bohan and Peter and with previous reported criteria for drug-induced myopathy in all cases. None of these patients had previous other connective tissue disorders. RESULTS: Five patients (median age 68 [54-78], female N =4) with CLD treatment (statin N =4, fenofibrates N =1) have developed iatrogenic polymyositis. All of them presented both proximal muscular weakness and increased muscle enzyme levels. One patient had iatrogenic antisynthetase syndrome characterized by mechanic's hand, Raynaud's phenomenon and anti JO1 antibodies. One other had sclerodermic hand oedema. Antinuclear antibodies were positive in 4 cases and muscle biopsy revealed polymyositis infiltrate in 4 cases. CLD treatment was discontinued with partial clinical improvement in 3 cases. Clinical remission was obtained with corticosteroid (N =5) in association with immunosuppresive agents in 3 cases. CONCLUSION: Muscular symptoms in patient with CLD treatment could be the first symptom of a polymyositis revealed or increased by this treatment and must encourage physician with antinuclear antibodies screening especially in case of proximal muscular weakness and increased muscle enzyme levels.

Localization of alpha-endosulphine in pancreatic somatostatin delta cells and expression during rat pancreas development.

AIMS/HYPOTHESIS: alpha-Endosulphine, a protein that belongs to the cAMP-regulated-phosphoprotein family, has been reported to modulate insulin secretion in vitro through interaction with the pancreatic beta-cell ATP-sensitive potassium (K(ATP)) channel. In this study, we analysed the tissue distribution of alpha-endosulphine and determined its pancreatic cellular localization. METHODS: Quantitative tissue distribution of alpha-endosulphine was studied by RIA on tissue extracts and cellular/subcellular localization was done using immunocytochemistry, morphometry and western blot analysis. alpha-Endosulphine and somatostatin release from RINT-3 somatostatin-secreting cells was quantified by RIA. RESULTS: alpha-Endosulphine, concentrated particularly in the central nervous system, was also detected in a wide variety of tissues including the pancreas. Immunohistochemistry analysis of adult rat pancreatic sections showed that alpha-endosulphine localized in somatostatin delta cells, where its expression increased during post-natal development. Immunoreactive cells were detected from foetal age E19, and the number of somatostatin cells co-expressing alpha-endosulphine increased with developmental age from E19 until adult. alpha-Endosulphine, highly expressed in the cytoplasm of RINT3 somatostatin-secreting cell line, was recovered in the particulate fraction of RINT3 cell extracts but was not co-secreted with somatostatin. CONCLUSION/INTERPRETATION: alpha-Endosulphine is expressed in all tissues tested including pancreas and is also detected in plasma. Pancreatic alpha-endosulphine is specifically localized in somatostatin delta cells. This cytosolic protein is not co-secreted with somatostatin and could be physically associated with particulate components of the cells. These findings are not in favour of an endocrine/paracrine effect of alpha-endosulphine on the beta-cell K(ATP) channel.

[Molecular mechanisms of insulin secretion]. / Mecanismes moléculaires de l'insulinosécrétion.

Insulin secretion from the beta-cells in the islets of Langerhans is mainly regulated by glucose entry via its transporter. The intracellular glucose metabolism induces a rise in ATP/ADP ratio which increases the degree of closure of ATP-sensitive potassium channels (K(ATP) channels), inducing a higher intracellular K+, which, in turn, depolarizes the membrane and opens voltage-sensitive calcium channels. The ensuing Ca2+ entry triggers extrusion of insulin-containing secretory granules and, thus, hormone secretion. The analysis of the structure of the genes encoding K(ATP) channels that are made of four Kir subunits (forming the ionic pore) and four regulatory SUR subunits (that contain the binding site for antidiabetic sulfonylureas) allowed to several subclasses of those ionic channels to be described: Insulin secreting beta cells contain the SUR1/Kir 6.2 complex, while heart and skeletal muscles contain the SUR2A/Kir 6.2 set, vascular smooth muscles (such as those present in coronary arteries) have SUR2B/Kir 6.1 and nonvascular smooth muscle SUR2B/Kir 6.2. The pharmacological specificity of each sulfonylurea depends on the type of SUR protein present in each tissue: most of the second generation sulfonylureas used in diabetic clinics (e.g. glibenclamide, glimepiride) display almost the same affinity for SUR1 SUR2A and SUR2B, leading to possible harmful adverse effects in type 2 diabetic patients with an associated cardiovascular pathology. In contrast, among the second generation sulfonylureas, only gliclazide displays a remarkable specificity towards the beta-cell K(ATP) channels, making this drug particularly safe in all situations, as it does not induce any interference with the cardiovascular system.

Oxyntomodulin inhibits pancreatic secretion through the nervous system in rats.

Glicentin (GLIC), oxyntomodulin (OXM), and peptide YY (PYY) released in blood by ileocolonic L-cells after meals may inhibit pancreatic secretion. Whereas OXM interacts with glucagon and tGLP-1 receptors, OXM 19-37, a biologically active fragment, does not. The purpose of this study was to measure the effect of OXM, OXM 19-37, GLIC, tGLP-1, and PYY on pancreatic secretion stimulated by 2 deoxyglucose (2DG), electrical stimulation of the vagus nerves (VES), acetylcholine and cholecystokinin octapeptide (CCK8) in anesthetized rats. The effect of OXM was also studied in dispersed pancreatic acini. Plasma oxyntomodulin-like immunoreactivity (OLI) was measured by radioimmunoassay after the exogenous infusion of OXM and after an intraduodenal meal. OXM 19-37, infused at doses mimicking postprandial plasma levels of OLI, decreased pancreatic secretion stimulated by 2DG, VES, or CCK8. Similar effects were found with OXM and GLIC. OXM 19-37 did not change the pancreatic stimulation induced by acetylcholine in vivo, or CCK-induced amylase release in isolated acini. Vagotomy completely suppressed the inhibitory effect of OXM 19-37 on CCK8-stimulated pancreatic secretion. PYY inhibited the effect of 2DG, but not that of CCK8, whereas tGLP-1, even in pharmacologic doses, had no effect on stimulated pancreatic secretion. OXM, OXM 19-37, but not tGLP-1, inhibit pancreatic secretion at physiologic doses, through a vagal neural indirect mechanism, different from that used by PYY, and probably through a GLIC-related peptide-specific receptor.

Endosulfines: Novel regulators of insulin secretion.

ATP-dependent potassium (K(ATP)) channels are at a key position in the control of insulin release from pancreatic beta-cells, as they couple the polarity of the cell membrane to the cell metabolism. These channels turn to a closed state when intracellular ATP rises, following an increase in glucose metabolism. These channels are also controlled by sulfonylureas, a class of drugs used in type 2 diabetic patients for triggering insulin secretion. We have obtained evidence of the existence of endogenous equivalents to sulfonylureas in the central nervous system and other K(ATP) channel-containing tissues (including the endocrine pancreas). These molecules, of a peptidic nature, have been called "endosulfines" (for "endogenous sulfonylureas"). In this review, we describe the discovery, isolation and biological features of these molecules--which represent novel regulators of insulin secretion--and the molecular cloning of the large molecular mass form (alpha-endosulfine), and discuss their possible implication in the physiology of beta-cells, as well as in pathology.

In vitro mechanism of action on insulin release of S-22068, a new putative antidiabetic compound.

1. The MIN6 cell line derived from in vivo immortalized insulin-secreting pancreatic beta cells was used to study the insulin-releasing capacity and the cellular mode of action of S-22068, a newly synthesized imidazoline compound known for its antidiabetic effect in vivo. 2. S-22068, was able to release insulin from MIN6 cells in a dose-dependent manner with a half-maximal stimulation at 100 micronM. Its efficacy (8 fold over the basal value), which did not differ whatever the glucose concentration (stimulatory or not), was intermediate between that of sulphonylurea and that of efaroxan. 3. Similarly to sulphonylureas and classical imidazolines, S-22068 blocked K(ATP) channels and, in turn, opened nifedipine-sensitive voltage-dependent Ca2+ channels, triggering Ca2+ entry. 4. Similarly to other imidazolines, S-22068 induced a closure of cloned K(ATP) channels injected to Xenopus oocytes by interacting with the pore-forming Kir6.2 moiety. 5. S-22068 did not interact with the sulphonylurea binding site nor with the non-I1 and non-I2 imidazoline site evidenced in the beta cells that is recognized by the imidazoline compounds efaroxan, phentolamine and RX821002. 6. We conclude that S-22068 is a novel imidazoline compound which stimulates insulin release via interaction with an original site present on the Kir6.2 moiety of the beta cell K(ATP) channels.

Isolation, characterization, and chromosomal localization of the human ENSA gene that encodes alpha-endosulfine, a regulator of beta-cell K(ATP) channels.

Human alpha-endosulfine is an endogenous regulator of the beta-cell K(ATP) channels. The recombinant alpha-endosulfine inhibits sulfonylurea binding to beta-cell membranes, reduces cloned K(ATP) channel currents, and stimulates insulin secretion from beta-cells. These properties led us to study the human ENSA gene that encodes alpha-endosulfine. Here, we describe the isolation, the partial characterization, and the chromosomal localization of the ENSA gene. The ENSA gene appears to be a 1.8-kb-long sequence that contains the transcription initiation site located 528 bp upstream of the initiation codon. The ENSA gene is intronless, and a single copy gene seems to be present in the genome. Finally, the ENSA gene co-localizes on human chromosome 14 (14q24.3-q31) with a locus for susceptibility to type 1 diabetes called IDDM11; thus, the ENSA gene represents an IDDM11 candidate.

Characterization of low-affinity binding sites for glibenclamide on the Kir6.2 subunit of the beta-cell KATP channel.

The ATP-sensitive K+ channel, an octameric complex of two structurally unrelated types of subunits, SUR1 and Kir6.2, plays a central role in the physiological regulation of insulin secretion. The sulfonylurea glibenclamide, which trigger insulin secretion by blocking the ATP-sensitive K+ channel, interacts with both high and low affinity binding sites present on beta-cells. The high affinity binding site has been localized on SUR1 but the molecular nature of the low affinity site is still uncertain. In this study, we analyzed the pharmacology of glibenclamide in a transformed COS-7 cell line expressing the rat Kir6.2 cDNA and compared with that of the MIN6 beta cell line expressing natively both the Kir6.2 and the SUR1 subunits. Binding studies and Scatchard analysis revealed the presence of a single class of low affinity binding sites for glibenclamide on the COS/Kir6.2 cells with characteristics similar to that observed for the low affinity site of the MIN6 beta cells.

Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway.

Using the MIN6 B-cell line, we investigated the hypothesis that miniglucagon, the C-terminal () fragment processed from glucagon and present in pancreatic A cells, modulates insulin release, and we analyzed its cellular mode of action. We show that, at concentrations ranging from 0.01 to 1000 pM, miniglucagon dose-dependently (ID50 = 1 pM) inhibited by 80-100% the insulin release triggered by glucose, glucagon, glucagon-like peptide-1-(7-36) amide (tGLP-1), or glibenclamide, but not that induced by carbachol. Miniglucagon had no significant effects on cellular cAMP levels. The increase in 45Ca2+ uptake induced by depolarizing agents (glucose or extracellular K+), by glucagon, or by the Ca2+channel agonist Bay K-8644 was blocked by miniglucagon at the doses active on insulin release. Electrophysiological experiments indicated that miniglucagon induces membrane hyperpolarization, probably by opening potassium channels, which terminated glucose-induced electrical activity. Pretreatment with pertussis toxin abolished the effects of miniglucagon on insulin release. It is concluded that miniglucagon is a highly potent and efficient inhibitor of insulin release by closing, via hyperpolarization, voltage-dependent Ca2+ channels linked to a pathway involving a pertussis toxin-sensitive G protein.