Mesoaxial polydactyly is a major feature in Bardet-Biedl syndrome patients with LZTFL1 (BBS17) mutations.

Ciliopathies are heterogeneous disorders sharing different clinical signs due to a defect at the level of the primary cilia/centrosome complex. Postaxial polydactyly is frequently reported in ciliopathies, especially in Bardet-Biedl syndrome (BBS). Clinical features and genetic results observed in a pair of dizygotic twins with BBS are reported. The following manifestations were present: retinitis pigmentosa, bilateral insertional polydactyly, cognitive impairment and renal dysfunction. X-rays of the hands confirmed the presence of a 4th mesoaxial extra-digit with Y-shaped metacarpal bones. The sequencing of LZTFL1 identified a missense mutation (NM_020347.2: p.Leu87Pro; c.260T>C) and a nonsense mutation (p.Glu260*; c.778G>T), establishing a compound heterozygous status for the twins. A major decrease of LZTFL1 transcript and protein was observed in the patient's fibroblasts. This is the second report of LZTFL1 mutations in BBS patients confirming LZTFL1 as a BBS gene. Interestingly, the only two families reported in literature thus far with LZTFL1 mutations have in common mesoaxial polydactyly, a very uncommon feature for BBS. This special subtype of polydactyly in BBS patients is easily identified on clinical examination and prompts for priority sequencing of LZTFL1 (BBS17).

Fatal bile pulmonary embolism after radiofrequency treatment of a hepatocellular carcinoma.

Radiofrequency is increasingly used to manage liver tumors. This report describes the case of a 74-year-old man who received two courses of percutaneous radiofrequency thermal ablation for a hepatocellular carcinoma over a 4-month period. He subsequently required computed tomography-guided drainage for an area of intrahepatic necrosis. During the procedure, hemobilia developed, followed by respiratory distress and collapse. The diagnosis of bile pulmonary embolism was established on the basis of high biliary acid concentrations in pulmonary fluid aspiration and blood plasma. Radiofrequency thermoablation provides local control of advanced liver tumors with low recurrence and morbidity. However, this interventional procedure risks damage to liver parenchyma involving vascular and biliary structures, which may lead to biliary-venous fistula and possible bile emboli.

Fatal form of phaeochromocytoma presenting as acute pyelonephritis.

We report the case of a young man who presented with a clinical picture of acute pyelonephritis. Within 3 h of admission, the patient developed acute respiratory distress associated with tachycardia and shock, and he was transferred to the intensive care unit. Mechanical ventilation of the lungs and symptomatic treatment were started immediately. Abdominal ultrasound revealed the presence of an adrenal tumour with central necrosis indicating a probable phaeochromocytoma. There was no sign of pyelonephritis. Ventricular fibrillation followed by asystole occurred soon after admission. The suddenness of the patient's death did not allow time for further investigation and therapy. The severity of the clinical signs was probably related to a massive release of catecholamines because of necrosis of the tumour, which may have been worsened by the diagnostic procedures performed to investigate the clinical symptoms and signs of acute pyelonephritis.

Gamma-hydroxybutyrate and cocaine administration increases mRNA expression of dopamine D1 and D2 receptors in rat brain.

The effects of acute and repeated gamma-hydroxybutyrate (GHB) and cocaine administration on D1 and D2 dopamine receptor mRNA expression were examined using in situ hybridization histochemistry in different rat brain structures rich in GHB receptors. Six hours after a single GHB administration (500 mg/kg i.p.), an increase in D1 and D2 mRNA expression was observed in almost all regions examined; whereas, acute cocaine injection (20 mg/kg i.p.) had no effect. Repeated exposure to GHB (500 mg/kg i.p. twice daily) for 10 days, followed by a 14-h withdrawal period, induced increasing effects on D1 and D2 dopamine receptor mRNA expression, similar to those caused by chronic treatment with cocaine (20 mg/kg i.p. once a day). These effects of GHB and cocaine on dopamine receptor mRNA expression could be a consequence, for both compounds, of the modulation of dopaminergic activity; thus, supporting the benefit of GHB in cocaine substitution therapy.

Prodynorphin and proenkephalin mRNAs are increased in rat brain after acute and chronic administration of gamma-hydroxybutyrate.

The effects of gamma-hydroxybutyrate (GHB) on prodynorphin (PD) and proenkephalin (PE) mRNA expression were examined using in situ hybridization histochemistry in discrete rat brain structures rich in GHB receptors. A single dose of GHB (500 mg/kg i.p.) increased striatal PE mRNA levels (+60%) between 15 and 90 min after injection. An increase in PD mRNA expression was observed in the frontal cortex (+90%) 6 h after GHB administration. Chronic exposure to GHB (500 mg/kg i.p. twice a day) for 10 days induced significant increases in both PE and PD mRNA levels in different brain regions examined, suggesting that PD and PE mRNA expressions are modulated by the endogenous GHBergic system.

The anxiolytic effect of gamma-hydroxybutyrate in the elevated plus maze is reversed by the benzodiazepine receptor antagonist, flumazenil.

The effects of gamma-hydroxybutyrate (GHB), a product of gamma-aminobutyric acid (GABA) metabolism which possesses neuromodulatory properties in brain, were investigated in the elevated plus maze in rats. The number of entries and the time spent in the open arms of the maze were increased by GHB (50, 150, 250 mg/kg i.p.). This is classically considered as indicative of an anxiolytic effect of the drug. There was no sedative effect at these doses as measured by the spontaneous locomotor activity in the actimeter or the total number of arm entries. The anxiolytic properties of GHB were reversed by neither the GHB receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5(H)-5-olylidene acetic acid) (300 mg/kg i.p.), nor the opioid receptor antagonist, naloxone (10 mg/kg i.p.). However the anti-anxiety effect of GHB was antagonized by the benzodiazepine receptor antagonist, flumazenil (10 mg/kg i.p.), suggesting an interaction of GHB with the GABA(A) receptor complex which mediates the anti-anxiety effect of benzodiazepines.