Evaluation of N-terminal prohormone B-type natriuretic Peptide in patients with acute coronary syndromes and percutaneous coronary intervention

The aim of this research was to describe N-terminal part of the prohormone B-type natriuretic peptide (NT-proBNP) levels over time in patients with acute coronary syndrome (ACS) before and after percutaneous coronary intervention (PCI). NT-proBNP, troponin I (Tn-I), creatine kinase (CK), CK MB isoenzyme (CKMB), fibrinogen, D-dimers, and C-reactive protein (CRP) were measured in 300 consecutive patients with ACS before undergoing successful reperfusion with PCI in the first 48 hours, 2 days after, and at the end of the 1st, 3rd, 6th, 12th, 18th, and 24th month. The concentration of NT-proBNP was cross-correlated with the levels of NT-proBNP in 300 patients without ACS and was significantly increased before and after PCI and at the end of the 3rd month, contrasting with the fast conversion to normal levels of Tn-I, CK, CKMB, fibrinogen, D-dimers, and CRP. In patients with ACS undergoing successful PCI, NT-proBNP shows slow kinetics, especially in patients with an increased thrombolysis in myocardial infarction risk score, hypertension, and diabetes. Nevertheless, cardiac neurohormonal activation may be a unifying feature among patients at high risk for cardiovascular events after ACS and PCI.     

Topical tacrolimus therapy of resistant cutaneous lesions in lupus erythematosus: a possible alternative

Objective. To determine the efficacy of tacrolimus ointment0.1% on resistant cutaneous lesions in patients with lupus erythematosus. Methods. Twelve patients with skin manifestations were studied.Six had discoid lupus (DL), four subacute cutaneous lupus erythematosus(SCLE) and two systemic lupus erythematosus (SLE). All patientshad extensive skin lesions refractory to previous treatment.Patients received topical tacrolimus 0.1% for a minimum of 6weeks and response was evaluated by physicians’ and patients’assessment and documented with photographs at baseline and atthe end of the treatment. Results. Eleven of 12 patients completed the therapy. One patientwith DL discontinued because of side-effects—peeling anda burning sensation. Six patients were clearly improved, onepatient had a minor remission of his face lesion while in fourthe rashes remained the same. Two patients with SCLE had significantregression of their lesions while the other two had no improvement.In DL, two had certain improvement, one minor improvement andtwo were without response. The patients with SLE had significantamelioration of their extensive photosensitive rash. Conclusion. Tacrolimus ointment 0.1% may be an effective alternativein patients with severe resistant cutaneous manifestations inlupus erythematosus. KEY WORDS: Tacrolimus, Cutaneous lupus erythematosus     

Unusual Right‐to‐Left Shunt by Single‐Sided Bilateral Inferior Vena Cava

Anomalous drainage of an inferior vena cava to the left atrium is a rare congenital cardiac anomaly that might lead to significant clinical implications. This report describes a 21‐year‐old male with an anomalous connection between one part of a single sided double inferior vena cava and the left atrium documented with cardiac imaging, including angiography. This rare congenital disorder should be considered in the differential diagnosis in patients with cyanosis and/or a history of paradoxical embolism. Interventional catheterization was the chosen method of intervention.     

Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53

We wished to examine the role of transforming growth factor-beta (TGF- beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G1 of the cell cycle, we examined the ability of TGF- beta to modulate two tumor suppressor proteins known to be critical regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti- Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled.     

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.     

High beta integrin expression is differentially associated with worsened pancreatic ductal adenocarcinoma outcomes

Outcomes in pancreatic ductal adenocarcinoma (PDAC) are known to be worse in tumors with high integrin β1 expression, but targeted monotherapy against this integrin has not been effective. Seven other beta integrins are expressed in mammalian biology and they are known to have overlapping and compensatory signaling in biological systems. However, their roles in PDAC are poorly understood and have not been systematically compared to integrin β1 biology. In this study, we analyzed the clinical outcomes against beta integrin 1-8 (ITGB1-8) expression in PDAC samples from two large independent cohorts, The Cancer Genome Atlas (TCGA) and {"type":"entrez-geo","attrs":{"text":"GSE21501","term_id":"21501"}}GSE21501. Biological function and tumor microenvironment composition were studied using Gene Set Enrichment Analysis and xCell. Expression of all eight beta integrins is significantly increased in PDACs relative to normal pancreatic tissues (all P<0.001). ITGB1, 2, 5, and 6 have similarly enriched gene patterns related to transforming growth factor (TGF)-β, epithelial mesenchymal transition, inflammation, stemness, and angiogenesis pathways. Homologous recombination defects and neoantigens are increased in high-ITGB4, 5, and 6 tumors, with decreased overall survival in high-ITGB1, 5, and 6 tumors compared to low expression tumors (hazard ratios 1.5-2.0). High-ITGB1, 2, and 5 tumors have increased fibroblast infiltration (all P<0.01) while endothelial cells are increased in high-ITGB2 and 3 tumors (all P<0.05). Overall, beta integrin expression does not correlate to immune cell populations in PDACs. Therefore, while all beta integrins are overexpressed in PDACs, they exert differential effects on PDAC biology. ITGB2, 5, and 6 have a similar profile to ITGB1, suggesting that future research in PDAC integrin therapy needs to consider the complementary signaling profiles mediated by these integrins.