Treatment of cardiogenic shock in peripartum cardiomyopathy: Case series from a tertiary ECMO center

Peripartum cardiomyopathy (PPCM) occurs toward the end of pregnancy or in the months after delivery without previously known structural heart disease. Development of therapy-refractory cardiogenic shock is described in the literature with a limited number of overall presented cases in this young patient cohort. To provide differences and key points in the therapy of end-stage PPCM patients, we present a case series of four young women with PPCM referred to our department for potential VA ECMO support.     

Distribution and ecological aspects of sand flies(Diptera:Psychodidae) species in Northeastern Iran

Objective:To determine both the distribution and the ecological characteristics of sand flies in Golestan Province,northeast of Iran in 2016.Methods:In this study,34 villages were selected based on their geographical conditions.Sticky paper traps were used for collecting the sand flies.Sampling was carried out in each of villages from May to November.In each village,60 traps for indoors and 60 for outdoors were monthly installed.The species of all collected sand flies were determined using approved morphological keys.Pearson coefficient correlation was used to find the relationship between the number of collected Phlebotomus papatasi from different villages and incidence rate of zoonotic cutaneous leishmaniasis as well as the number of positive cases of the disease.The altitude of the studied villages was extracted from digital elevation model of the area using GIS and vegetation cover density index of the province was extracted from Modis satellite imagery and distribution map of sand flies drown up.Results:Overall,5 428 sand flies were collected and identified,belonging to 18 species.Phlebotomus wenyoni was reported for the first time from the area in this study.The frequency of sand flies in the villages located in northeast of the Golestan province(the plateau area,lower altitude,arid and semi-arid climates,and lower vegetation cover density),were more than other villages in this province.There was a significant correlation between the number of collected Phlebotomus papatasi and incidence rate of the zoonotic cutaneous leishmaniasis cases in different villages(r=0.837,P=0.019) as well as the number of positive cases of the disease(r=0.688,P0.001).Conclusions:In the northeaster areas of Golestan Province which is known as the endemic foci of zoonotic cutaneous leishmaniasis,the abundance of sand flies were more and the conditions for their growth and development were more appropriate.     

Leishmanization: use of an old method for evaluation of candidate vaccines against leishmaniasis

To establish the safety and reproducibility of live challenge with Leishmania major, a single frozen stabilate was used in two open, single-arm leishmanization (LZ) trials. A total of 42 inoculations in 28 male adult volunteers were followed until complete healing. Lesions induced by LZ are as diverse as natural infection, but much milder. Total protection was seen in 100% (11/11) of recovered volunteers. LZ used as live challenge to test vaccine candidates reduces the required sample size, is cost effective for surrogate markers studies and will induce protection in the participants who are not protected by candidate vaccines.     

Differential effects of rapamycin, cyclosporine A, and FK506 on human coronary artery smooth muscle cell proliferation and signalling

BACKGROUND: Immunosuppressive agents are at the forefront of preventing organ rejection after transplantation. However, their effects on vascular smooth muscle cell-mediated intimal hyperplasia that occurs in post-transplant coronary artery disease are less well known. METHODS AND RESULTS: We investigated the in vitro effects of three immunosuppressive agents cyclosporine A (CsA), FK506 (tacrolimus), and rapamycin (sirolimus, Rapa) on cultured human coronary artery smooth muscle cells (cSMC). CsA inhibited both platelet-derived growth factor (PDGF)-stimulated DNA synthesis and serum-induced proliferation at high concentrations (> or =1000 ng/ml). The growth-inhibitory effect of CsA was not altered by anti-TGF-beta neutralising antibodies nor was autocrine TGF-beta release detected in CsA-treated culture medium. At inhibitory doses, CsA inhibited ERK kinase activation by PDGF, although cytotoxicity was also apparent. Most notably, CsA visibly prevented PDGF-induced altered cell morphology. Rapa was a highly potent and effective inhibitor of cSMC proliferation (reduction in DNA synthesis by >50% from 0.01 ng/ml), acting through inhibition of 70-kDa S6 kinase (p70S6k). FK506 (1-1000 ng/ml) did not affect cSMC proliferation alone, although a > or =250-fold excess of FK506 over Rapa completely reversed the inhibitory effect of Rapa, confirming that these two agents share a common intracellular receptor, the FK506-binding protein (FKBP). CONCLUSION: Rapa is a powerful inhibitor of cSMC proliferation, while CsA slighly inhibits cSMC proliferation, although only at higher concentrations that may be toxic. These results indicate that therapeutic immunosuppression with Rapa may be additionally useful in prevention or delay of posttransplant coronary artery disease.     

Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors

OBJECTIVES/HYPOTHESIS: Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer. STUDY DESIGN: We have used fluorescence in situ hybridization (FISH) to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. Both single- and dual-color FISH were performed. METHODS: Paraffin-embedded tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 centromeric probes as a control. Twenty-eight of these samples were analyzed for p16 expression by immunohistochemistry. RESULTS: Cyclin D1 amplification was observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of p16 expression was observed in 64% (18/28) of patients. There was a good correlation between the deletion of p16 sequences and the loss of p16 expression (P = .008). Amplification of cyclin D1 had a statistically significant association with recurrence, distant metastasis, and survival at 36 months. There was a significant association between p16 deletion and the development of distant metastases. Cyclin D1 amplification and p16 deletion together correlated with recurrence, distant metastasis, and survival. CONCLUSIONS: We demonstrate that FISH is a simple and sensitive method for detecting cyclin D1 amplification and p16 deletion in head and neck cancer. Our results suggest that these two genetic aberrations together portend a poorer outcome than either of the abnormalities alone in head and neck cancer.