Agenesis of the Gallbladder Revisited Laparoscopically

Gallbladder agenesis is an extremely rare disease. Necropsy incidence has been reported to be 0.016%. Failure lo locate the gallbladder at the time of a planned cholecystectomy can be very challenging. We report such a case during a laparoscopic cholecystectomy. The indication for surgery in these patients are complaints of gallbladder symptoms along with a false-positive ultrasound study. During exploration, an abnormal location of the gallbladder has to be excluded. Ectopic gallbladder locations include intrahepatic, lesser omentum, retroperitoneal, retrohepatic, within the falciform ligament, retroduodenal, and retrohepatic areas. Thorough exploration and cholangiography are essential. Embryologically, the gallbladder and cystic duct arise from the caudal portion of the hepatic bud. All of the previously reported cases of gallbladder agenesis have shown an absence of both the gallbladder and cystic duct. We report an embryological oddity wherein a patent cystic duct was found along with an agenetic gallbladder. This is the first case report of this finding, along with this being the first absent gallbladder discovered laparoscopically.     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

Inborn errors of the urea cycle

Inborn errors of the urea cycle are an important cause of hyperammonaemia throughout childhood, and are associated with high morbidity and mortality rates. If they are diagnosed early and treated appropriately, the outcome for affected children is significantly improved.     

Warfarin or Low-Molecular-Weight Heparin Therapy does not Prolong Pig-To-Primate Cardiac Xenograft Function

Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an alpha-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin, Group 2 (n = 13) with LMWH and Group 3, received no anti-coagulant drugs. The median duration of xenograft function was 20 days (range 3-62 days), 18 days (range 5-109 days) and 15 days (range 4-53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anti-coagulant strategies to achieve long-term xenograft function cannot be excluded.     

Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

BACKGROUND: Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. METHODS: Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. RESULTS: Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. CONCLUSIONS: Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.