Biliary metastases of breast carcinoma. The case for resection

Obstructive jaundice developed in two patients 6 and 8 years after surgery for breast carcinoma. In both patients exploration disclosed a tumor of the hilus which was a biliary metastasis of breast cancer. Surgical resection was performed. Examination of the resected specimen showed infiltration of the duct walls by sheets of metastatic carcinomatous cells from the previous breast cancer. The postoperative course was uneventful in both patients with disappearance of all symptoms due to the biliary obstruction. The first patient died 4 years later from peritoneal deposits and the second was alive at 30 months with a metastasis to the hip. These observations differ from most of those previously reported, by the localization of the tumor at the hilus and the direct infiltration of the duct walls by the tumor. The results of this study suggest that aggressive surgical treatment may be the treatment of choice in patients with extrahepatic biliary metastases of breast carcinoma.     

The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia–reperfusion injury

Objective: Ischemia–reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H₂S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H₂S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size (% of AAR) in controls was 47.4 ± 6.2% vs 20.1 ± 3.3% in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0% (p = 0.10) and 45.1% (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.     

Genetic contributions of the serotonin transporter to social learning of fear and economic decision making

Serotonin (5-HT) modulates emotional and cognitive functions such as fear conditioning (FC) and decision making. This study investigated the effects of a functional polymorphism in the regulatory region (5-HTTLPR) of the human 5-HT transporter (5-HTT) gene on observational FC, risk taking and susceptibility to framing in decision making under uncertainty, as well as multidimensional anxiety and autonomic control of the heart in healthy volunteers. The present results indicate that in comparison to the homozygotes for the long (l) version of 5-HTTLPR, the carriers of the short (s) version display enhanced observational FC, reduced financial risk taking and increased susceptibility to framing in economic decision making. We also found that s-carriers have increased trait anxiety due to threat in social evaluation, and ambiguous threat perception. In addition, s-carriers also show reduced autonomic control over the heart, and a pattern of reduced vagal tone and increased sympathetic activity in comparison to l-homozygotes. This is the first genetic study that identifies the association of a functional polymorphism in a key neurotransmitter-related gene with complex social–emotional and cognitive processes. The present set of results suggests an endophenotype of anxiety disorders, characterized by enhanced social learning of fear, impaired decision making and dysfunctional autonomic activity.     

Erythema nodosum in association with celiac disease

We present a 16-year-old girl with a 4-year history of chronic persistent erythema nodosum. Recurrently low serum iron values suggested the possibility of a malabsorption syndrome. The presence of antitransglutaminase and antiendomysium antibodies and the jejunal biopsy specimen findings showed an underlying celiac disease. On a strict gluten-free diet, the skin lesions resolved and the girl has since remained symptom free for 9 months. Thus celiac disease can be a triggering factor for erythema nodosum. In the chronic form of the skin lesions, serologic testing for this specific enteropathy may be justified.     

Effects of PACAP on Mitochondrial Apoptotic Pathways and Cytokine Expression in Rats Subjected to Renal Ischemia/Reperfusion

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with highly efficient cytoprotective actions. Its neuroprotective effects are well-known, but PACAP is able to exert similar actions in non-neuronal cells. Recently, we have shown that PACAP prolongs renal ischemic time, decreases mortality, and attenuates tubular degeneration in a rat model of renal ischemia/reperfusion, but the mechanism of renoprotection is not yet known. Therefore, the aim of the present study was to obtain further insight into the renoprotective effects of PACAP by examining its direct effects of PACAP on mitochondrial permeability transition in vitro and on the expression of the anti-apoptotic Bcl-2 and cytokines/chemokines in kidney tissues following 45 and 60 min renal ischemia and reperfusion in vivo. We found that PACAP did not have any direct effect on mitochondrial permeability transition. Cytokine array revealed that the expression of a few cytokines/chemokines was strongly increased after ischemia/reperfusion, which was ameliorated by PACAP treatment. Furthermore, in rats subjected to renal ischemia, PACAP treatment counteracted the ischemia/reperfusion-induced decrease of the anti-apoptotic Bcl-2, both after 45 and 60 min ischemia, as analyzed by Western blot. In summary, we showed that PACAP could attenuate tissue injury involving both anti-inflammatory and anti-apoptotic effects, but not directly acting on mitochondrial permeability transition.