Time course of caspase activation in selectively vulnerable brain areas following global cerebral ischemia due to cardiac arrest in rats

This study evaluated the time course of caspase activation in selectively vulnerable brain areas (hippocampus, nucleus reticularis thalami (NRT), cortex and striatum) following cardiopulmonary resuscitation (CPR) after global cerebral ischemia due to cardiac arrest (CA) in rats. Caspases are well known to play a crucial role in the apoptotic cascade and inflammatory syndromes and, therefore, represent potential therapeutic postischemic targets. Given the delayed neurodegeneration following CA, it is highly important to study the time course of caspase activation in regard to therapeutic interventions after CA. To assess caspase activity, in situ staining was applied to detect general caspase activity at 6h, 3d and 7d and caspase-3 activity at 3d after return of spontaneous circulation (ROSC). For detection of neuronal apoptosis, TUNEL staining was applied at 7d after ROSC. Distinct patterns of early caspase activation were observed at 6h and 3d in the NRT and striatum and of late activation at 7d in the hippocampal CA-1 sector. General caspase and caspase-3 activity correlated strongly at 3d after ROSC in all areas studied. At 7d, the TUNEL-positive neuron counts in the hippocampal CA-1 sector correlated strongly with caspase activation. In conclusion, general caspase and caspase-3 activity after 6 min of CA and the delayed occurrence of TUNEL-positive neurons strongly indicate that neuronal degeneration after CA is at least strongly associated with apoptosis. Therefore, postischemic antiapoptotic interventions might offer potential future therapeutic opportunities global cerebral ischemia due to CA.     

Imerslund-Gräsbeck syndrome in a 15-year-old German girl caused by compound heterozygous mutations in CUBN

Imerslund-Gräsbeck syndrome (IGS) is a recessive disorder of intestinal cobalamin (Cbl) absorption and renal tubular protein reabsorption sometimes accompanied by urinary tract malformation. Mutations in the cubilin (CUBN) and amnionless (AMN) genes have been described as causal defects. CUBN and AMN proteins form the cubam complex that functions as the receptor for the intrinsic factor-Cbl (IF-Cbl) complex in the ileum and for proteins found in the primary urine in the kidney. We report the case of a 15-year-old German girl who presented with megaloblastic anaemia and funicular myelosis due to Cbl-deficiency and selective proteinuria. We clinically diagnosed- and for the first time in a patient of German ancestry-genetically confirmed IGS by detecting a compound heterozygous gene deletion and missense mutation in the CUBN gene. In conclusion IGS should be considered in paediatric patients presenting with symptoms like megaloblastic anaemia, funicular myelosis and benign proteinuria. Diagnosis should be confirmed genetically to avoid further invasive diagnostics, administer proper lifelong treatment and offer genetic counselling.     

Spontaneous bladder rupture in non-augmented bladder exstrophy

Childhood spontaneous bladder rupture is an uncommon event, usually associated with bladder augmentation. Occasionally it occurs in normal bladders or non-augmented bladders with a predisposing factor. We present a unique case of misdiagnosed spontaneous bladder rupture in a non-augmented bladder exstrophy patient without evidence of lower urinary outlet obstruction. His acute abdomen mimicked appendicitis and was managed with laparoscopic exploration, intraperitoneal fluid drainage, appendectomy and bladder drainage. This case highlights the need for pediatric urological consultation by surgeons in the case of an acute abdomen with free fluid in a patient with an abnormal bladder.     

Risk factors for signs and symptoms of TMD in a rural adult southeast Tanzanian population

The aim of this study was to determine some risk factors for signs and symptoms of temporomandibular disorders (TMD) in a rural adult population of Southeast Tanzania. Two hundred and eighteen adults aged 40+ years participated in the study. Joint clicking was significantly higher (p < 0.024) in the adults aged 60+ years than in the younger age group. Limited jaw opening was higher in females than males (chi2 = 46.4 on 2 df; p < 0.001), and there was a significant association between the type of toothbrush and limitation in jaw opening (chi2 = 156.6 on 4 df; p < 0.001). The results suggest that the use of miswaki (chewing sticks) and advanced age are risk factors for the high prevalence of signs and symptoms of TMD in this rural population. Further studies are recommended to control for other confounding factors such as socio-economic status.     

Postendoscopic retrograde cholangiopancreatography pancreatitis: a rare cause of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome

Endothelial injury is perhaps the inciting factor leading to the microangiopathic process that initiates thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). TTP-HUS after postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is extremely rare, but potentially is life threatening. Here, we describe a case of a 23-year-old man with a history of choledocholithiasis, who developed TTP-HUS, 2 days after the onset of post-ERCP pancreatitis. It is important that physicians recognize TTP-HUS as one of the potential causes of acute kidney injury in cases of acute pancreatitis and post-ERCP pancreatitis for adult patients, especially when there is concomitant thrombocytopenia and hemolytic anemia. The early initiation of plasma exchange has a major impact on the survival and preservation of renal function. Exchange transfusion of fresh frozen plasma remains the cornerstone treatment of TTP-HUS.