Surgical resection for non-Asian intrahepatic lithiasis: The Brazilian experience

BackgroundIntrahepatic lithiasis (IHL) is a rare disease in the western world. Complications associated with IHL include acute cholangitis, liver atrophy, secondary biliary cirrhosis, and risk for intrahepatic cholangiocarcinoma. Liver resection is considered the treatment of choice for IHL. The objective of this study was to analyze patients who underwent liver resection for non-Asian hepatolithiasis.Methods127 patients with symptomatic non-Asian hepatolithiasis underwent resection in six institutions. Demographic data, clinical presentation, diagnosis, classification according to stone location, presence of atrophy, bile duct stricture, biliary cirrhosis, incidence of cholangiocarcinoma, treatment and postoperative course were evaluated.Results52 patients (40.9%) were male and the mean age was 46.1 years. Sixty-six patients (51.9%) presented with history of cholangitis. Stones were located in the left lobe in 63 (49.6%), and right lobe in 28 patients (22.0%). Atrophy was observed in 31 patients (24.4%) and biliary stenosis in 18 patients (14.1%). The most common procedure performed was left lateral sectionectomy in 63 (49.6%) patients, followed by left hepatectomy in 36 (28.3%), right hepatectomy in 19 (15.0%), and associated hepaticojejunostomy in 28 (22.0%). Forty-two patients (33.0%) presented postoperative complications and the most common were biliary fistula (13.3%) and surgical site infection (7.0%). Postoperative mortality was 0.7%. Intrahepatic cholangiocarcinoma was observed in 2 patients (1.5%). Recurrence was identified in 10 patients (7.8%), mostly with bilateral stones and/or hepaticojejunostomy.ConclusionLiver resection is the standard treatment for symptomatic unilateral or complicated IHL with good operative results. Risk of cholangiocarcinoma was low in non-Asian patients.     

Tumor necrosis factor-alpha -308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans

The aim of this study was to determine the frequency and potential relevance of the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha) in the severity of rheumatoid arthritis (RA) in Mexicans. HLA-DR and polymorphisms at positions -238 and -308 of TNF-alpha gene were determined in 137 Mexican RA patients (44 with severe and 93 with non-severe RA) as well as in 169 healthy controls (99 were typed for HLA-DR). We observed an increased frequency of HLA-DR4 in severe RA compared to healthy controls (pC=0.02, OR=2.33). TNF polymorphism analysis showed a significant increased frequency of TNF -238 GG genotype in the whole group of RA patients when compared to healthy controls (pC=0.007, OR=4.71). When the analyses were carried out separately in severe and non-severe RA patients, the increased frequency of -238 GG genotype only was observed in patients with non-severe forms of the disease. Analysis of -308 polymorphism showed increased frequency of -308 T2 (A) allele in severe RA when compared to non-severe disease (pC=0.011, OR=3.29) and to healthy controls (pC=0.002, OR=3.97). The data demonstrate that -308 T2 (A) allele is associated with susceptibility to develop severe RA in Mexicans. This association could be independent from HLA-DR alleles and might be used as a prognostic marker for severe RA.     

Mixed Hyperbranched/Triblock Copolymer Micelle Assemblies: Physicochemical Properties and Potential for Drug Encapsulation

Mixed micelles have numerous advantages while requiring little to no effort in preparation. This study aims to produce mixed micelle nanostructures from a linear triblock copolymer and a hyperbranched random copolymer, and is able to be loaded with the weakly water-soluble drugs curcumin and indomethacin. Different preparation techniques are employed to produce mixed micelles comprised of Pluronic F127 block copolymer, and hyperbranched poly[(ethylene glycol) methyl ether methacrylate-co-lauryl methacrylate], H-[P(OEGMA-co-LMA)], copolymer. Few studies have dabbled in these types of coassemblies, which provides insight into how structural differences of each copolymer can affect the formation of micelles. To determine the properties of the emerging nanostructures in aqueous environments, including their size, homogeneity, and surface charge, different physicochemical techniques are used, such as light scattering and spectroscopic methods. The results reveal that the copolymers combine, and spontaneously self-assemble into mixed micelle-like nanostructures in aqueous environments, whereas both systems of neat and drug-loaded nanostructures exhibit desirable properties such as small average micelle hydrodynamic radii and low size polydispersity indices. The nanostructures that result from the effective encapsulation of curcumin exhibit outstanding stability over 169 days. The fluorescent qualities of curcumin persist after encapsulation, making the novel nanostructures excellent candidates for bioimaging applications.     

Classic Adamantinoma with Osteofibrous Dysplasia-like Foci and Secondary Aneurysmal Bone Cyst

Adamantinoma, a rare bone lesion of the tibia and fibula, has two distinct variants, classic adamantinoma and osteofibrous dysplasia-like adamantinoma. Composite lesions have not been described. Aneurysmal bone cyst is a benign cystic lesion which may also occur in the tibia and fibula. We report an unusual case of classic adamantinoma with osteofibrous dysplasia-like areas and foci of secondary aneurysmal bone cyst with prominent giant cells. A lesion was diagnosed in a 17-year-old girl with a 14-year history of a slowly enlarging left tibial mass and increasing deformity. Pathologically, the predominant pattern was classic adamantinoma, with minor foci of osteofibrous dysplasia-like adamantinoma and areas of secondary aneurysmal bone cyst with abundant multinucleated giant cells. We report the clinical, radiologic, and pathologic features of this case, and summarize lesions associated with secondary aneurysmal bone cyst. To our knowledge, the association of adamantinoma with secondary aneurysmal bone cyst has not been previously reported.     

The metabolic syndrome among postmenopausal women in Ecuador.

BACKGROUND: The prevalence of the metabolic syndrome increases with age and after the onset of menopause, and may explain in part the apparent acceleration of cardiovascular disease in postmenopausal women. OBJECTIVE: To determine the prevalence of metabolic syndrome and related risk determinants among postmenopausal women in Ecuador. METHODS: Postmenopausal women >or=40 years of age, non-users of hormone therapy and with an intact uterus, were asked to participate in a metabolic syndrome screening and educational program at the Institute of Biomedicine of the Universidad Católica of Guayaquil, Ecuador. Sociodemographic data, waist circumference and blood pressure measurements were recorded, and a fasting blood sample obtained for serum glucose and lipid profile determinations. Woman were counseled and managed according to the results. Metabolic syndrome was defined in accordance with the criteria of the Third Adult Treatment Panel (ATP III). RESULTS: Three hundred and twenty-five postmenopausal women entered the program. Mean (+/-standard deviation) age was 55.9 +/- 8.1 years, 53.5% of them were aged >or=54 years (median). The prevalence of metabolic syndrome, according to ATP III criteria, was 41.5%. Using the same criteria, 38.8%, 16.6%, 56.9% and 54.2% of the women presented with hypertension, diabetes, hypertriglyceridemia and abdominal obesity, respectively. More than 40% of women determined to have hypertension or diabetes lacked knowing so. Logistic regression analysis determined that age increased the risk of presenting hypertension and diabetes (odds ratio (95% confidence interval): 2.0 (1.2-3.2) and 1.6 (0.9-3.0), respectively, p < 0.05), entities which in turn duplicated the risk of having high triglyceride levels. Sedentary women with <5 years since menopause onset were at higher risk of having abdominal obesity, which was directly related to diabetes and hypertension. CONCLUSIONS: In this postmenopausal Ecuadorian population the prevalence of the metabolic syndrome was high and its determinant factors related to age, time since menopause onset and sedentary habits. Because of the implications for cardiovascular risk, counseling programs directed toward high-risk populations should be encouraged.     

Targeting cancer by binding iron: Dissecting cellular signaling pathways

Newer and more potent therapies are urgently needed to effectively treat advanced cancers that have developed resistance and metastasized. One such strategy is to target cancer cell iron metabolism, which is altered compared to normal cells and may facilitate their rapid proliferation. This is supported by studies reporting the anti-neoplastic activities of the clinically available iron chelators, desferrioxamine and deferasirox. More recently, ligands of the di-2-pyridylketone thiosemicarbazone (DpT) class have demonstrated potent and selective anti-proliferative activity across multiple cancer-types in vivo, fueling studies aimed at dissecting their molecular mechanisms of action. In the past five years alone, significant advances have been made in understanding how chelators not only modulate cellular iron metabolism, but also multiple signaling pathways implicated in tumor progression and metastasis. Herein, we discuss recent research on the targeting of iron in cancer cells, with a focus on the novel and potent DpT ligands. Several key studies have revealed that iron chelation can target the AKT, ERK, JNK, p38, STAT3, TGF-β, Wnt and autophagic pathways to subsequently inhibit cellular proliferation, the epithelial-mesenchymal transition (EMT) and metastasis. These developments emphasize that these novel therapies could be utilized clinically to effectively target cancer.     

A Case of Compound Mutations in the MYBPC3 Gene Associated with Biventricular Hypertrophy and Neonatal Death

Hypertrophic cardiomyopathy (HCM) is a familial, genetically determined, primary cardiomyopathy caused by mutations in genes coding for proteins of the sarcomere, or, less frequently, genes involved in storage diseases. In pediatric settings, pure HCM has an estimated incidence of 4.7 per million children. The disease is often sub-clinical and goes unrecognized mainly because most patients with HCM have only mild symptoms, if any. However, sudden cardiac death, the most dramatic clinical occurrence and the primary concern for patients and physicians alike, may be the first manifestation of the disease. We describe a case of compound heterozygosity in the MYBPC3 gene (p.Glu258Lys and IVS25-1G>A) associated with biventricular hypertrophy, atrial enlargement and subsequent neonatal death 33 days postpartum. Other studies have reported compound and/or double heterozygosis in the same or different sarcomeric genes during childhood and adulthood, and neonatal presentations have also been described. Our observations show that the combination of a missense (p.Glu258Lys) and a splice-site mutation (IVS25-1G>A) profoundly affects the clinical course. In families in which parental mutations are known, preimplantation (where ethically and legally feasible) or prenatal genetic screening should be adopted because: (1) neonatal HCM in genetic heterozygosity is potentially lethal and (2) heart disease is the most common developmental malformation and the leading cause of neonatal mortality and morbidity.