Burden of significant liver damage in people living with HIV after microelimination of the hepatitis C virus.

BACKGROUND: Once HIV/HCV-coinfection microelimination has been virtually achieved in some countries, there is no information about the burden of liver disease among people living with HIV (PLWH). The aim of this study was to define the current prevalence and causes of significant liver damage (SLD) in PLWH. METHODS: Cross-sectional study including 619 PLWH. SLD was defined as liver stiffness (LS) ≥ 7.2 kPa measured by transient elastography. Nonviral liver damage (NVLD) was considered if there was no evidence injury due to chronic hepatitis C virus (HCV) infection, active hepatitis B (HBV) or E virus infections. RESULTS: One hundred and twelve of 619 (18.2%) PLWH showed SLD, including 34/112 (5.5%) with LS ≥14 kPa. 72/112 (64.3%) had cured HCV infection, 4/112 (3.6%) active HBV infection, and 2/112 HBV/prior HCV coinfection. Thus, 40 (35.7%) showed NVLD. Metabolic associated steatohepatitis (MASH) was present in 29/40 (72.5%) of patients with NVLD, alcoholic liver damage in 2/40 (2.5%) and mixed steatohepatitis in 5/40 (12.5%). CONCLUSIONS: After HIV/HCV microelimination the burden of liver damage is high among PLWH. Persistent injury after HCV is a very frequent cause of SLD. However, NVLD, mainly due to MASH, is also a common condition in this population.

Similar prevalence of hepatic steatosis among patients with chronic hepatitis C with and without HIV coinfection.

Hepatic steatosis (HS) is frequently observed in HIV-infected patients. It is not known whether HIV infection is an independent risk factor for HS development. We aimed to analyze whether HIV coinfection was associated with a higher frequency of HS in patients with chronic hepatitis C. This was a retrospective cross-sectional study. 574 subjects with chronic hepatitis C virus (HCV) infection were included, 246 (43%) of them coinfected with HIV. All of them underwent transient elastography with controlled attenuation parameter (CAP) measurement. HS was defined as CAP ≥ 248 dB/m. 147 individuals (45%) showed HS in the HCV-monoinfected group and 100 (40.7%) in the HIV/HCV-coinfected group (p = 0.318). HS was associated with body mass index (BMI) [<25 Kg/m2 vs. ≥25 Kg/m2, 67 (23.5%) vs. 171 (62.9%); p = 0.001], with plasma HDL-cholesterol [<50 mg/dL vs. ≥50 mg/dL, 122 (48.6%) vs. 95 (37.5%), p = 0.012], with plasma triglycerides [<150 mg/dL vs. ≥150 mg/dL, 168 (40.2%) vs. 65 (52.4%); p = 0.016] and with plasma total cholesterol [<200 mg/dL vs. ≥200 mg/dL, 181 (41%) vs. 53 (52.5%); p = 0.035]. In the multivariate analysis, HS was associated with BMI [adjusted OR (AOR) = 1.264 (1.194-1.339); p = 0.001], age [AOR = 1.029 (1.001-1.058); p = 0.047] and HCV genotype 3 infection [AOR = 1.901 (1.081-2.594); p = 0.026]. HIV coinfection was not associated with HS [AOR = 1.166 (0.719-1.892); p = 0.534]. In conclusion, HIV coinfection is not related with an increased frequency of HS in HCV-infected patients.

Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients

Purpose. The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients. Materials and methods. A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction. Results. The median follow-up was 16 months (range, 1-70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022). Conclusion. This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy (AU)

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Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients.

PURPOSE: The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction. RESULTS: The median follow-up was 16 months (range, 1-70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022). CONCLUSION: This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.

Whole-genome transcriptional analysis of Escherichia coli during heat inactivation processes related to industrial cooking.

Escherichia coli K-12 was grown to the stationary phase, for maximum physiological resistance, in brain heart infusion (BHI) broth at 37°C. Cells were then heated at 58°C or 60°C to reach a process lethality value \[\mathbf{\left(}{{\mathit{F}}^{\mathit{o}}}_{\mathbf{70}}^{\mathbf{10}}\mathbf{\right)} \] of 2 or 3 or to a core temperature of 71°C (control industrial cooking temperature). Growth recovery and cell membrane integrity were evaluated immediately after heating, and a global transcription analysis was performed using gene expression microarrays. Only cells heated at 58°C with F(o) = 2 were still able to grow on liquid or solid BHI broth after heat treatment. However, their transcriptome did not differ from that of bacteria heated at 58°C with F(o) = 3 (P value for the false discovery rate [P-FDR] > 0.01), where no growth recovery was observed posttreatment. Genome-wide transcriptomic data obtained at 71°C were distinct from those of the other treatments without growth recovery. Quantification of heat shock gene expression by real-time PCR revealed that dnaK and groEL mRNA levels decreased significantly above 60°C to reach levels similar to those of control cells at 37°C (P < 0.0001). Furthermore, despite similar levels of cell inactivation measured by growth on BHI media after heating, 132 and 8 genes were differentially expressed at 71°C compared to 58°C and 60°C at F(o) = 3, respectively (P-FDR < 0.01). Among them, genes such as aroA, citE, glyS, oppB, and asd, whose expression was upregulated at 71°C, may be worth investigating as good biomarkers for accurately determining the efficiency of heat treatments, especially when cells are too injured to be enumerated using growth media.

Estudio farmacocinético de la asociación atorvastatina 40 mg + ezetimibe 10 mg tabletas / I study farmacocinetico of the association of atorvastatina 40 mg ezetimibe of 10 mg tablets

Determinar la Biodisponibilidad en una dosis única, de Atorvastatina 40 mg + Ezetimibe 10 mg tabletas, con evaluación de los parámetros farmacocinéticos de concentración máxima en el organismo (C Máx), área bajo la curva de los niveles en el organismo (AUC 0→t y AUC 0 →∞)tiempo en alcanzar la concentración máxima (T Máx), tiempo de vida media (t 1/ 2) y constante de eliminación (Ke). El estudio de Biodisponibilidad se desarrolló mediante la determinación de la magnitud y la velocidad de la absorción “in vivo” de la asociación Atorvastatina 40 mg + Ezetimibe 10 mg tabletas, fabricadopor Laboratorios La Santé S.A, en voluntarios sanos. 12 voluntarios sanos, hombres y mujeres, con edades comprendidas entre los 18 y 55 años, con un peso de ± 15% del apropiado según la edad y la talla, que cumplieron a cabalidad con todos los exámenes clínicos efectuados antes del estudio para su selección y que no presentaron alguna anomalía en su historia médica, recibieron una dosis única de la asociación 40 mg de Atorvastatina + 10 mg de Ezetimibe tabletas, fabricado por Laboratorios La Santé S.A. vía oral con administración de 240 mL de agua. Después de su administración se tomaron muestras de sangre de cada voluntario a los siguientes tiempos: 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 36.0, 48.0 y 72.0 horas. El análisis de las muestras se realizó por Cromatografía Líquida de Alta Resolución (HPLC) con detección UV, previa extracción de los analitos (extracción líquido/líquido), en el Laboratorio bioanalítico de Delivery Technologies. La determinación de la magnitud y la velocidad de la absorción “in vivo” de Atorvastatina 40 mg + Ezetimibe 10 mg tabletas, se evaluó comparando con los parámetros farmacocinéticos ya reportados en estudios previos de estos principios activos por separados...

To determine the bioavailability in a single dose of Atorvastatin 40 mg + Ezetimibe 10 mg tablets, with assessment of pharmacokinetic parameters of maximum concentration body (C max), area under the curve of the levels in the organism (AUC 0 → t and AUC 0 → ∞), time to reach maximum concentration (T max), half-life (t 1 / 2) and elimination constant (Ke). The bioavailability study was conducted by  determining the magnitude and rate of absorption in vivo of the association Atorvastatin 40 mg + Ezetimibe 10 mg tablets manufactured by Laboratorios La Sante SA, in healthy volunteers. 12 healthy volunteers, men and women, aged between 18 and 55, with a weight of ± 15%  according to the age and size, which fully met  with all the clinical examinations performed prior to study and not presenting any anomaly in these tests, received a single dose of the association Atorvastatin 40 mg + Ezetimibe 10 mg tablets, manufactured by Laboratorios La Santé SA, with oral administration of 240 mL of water. After administration of the drug. blood samples were taken from each volunteer at the following times: 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 36.0, 48.0 and 72.0 hours. The sample analysis was performed by High Resolution liquid chromatography (HPLC) with UV detection after extraction of analytes (liquid-liquid extraction) in the bioanalytical laboratory of Delivery Technologies. The determination of the magnitude and absorption rate in vivo of Atorvastatin 40 mg + Ezetimibe 10 mg tablets, was evaluated by comparing with the Pharmacokinetic parameters reported in previous studies of these drug by separate. Adverse Events Report: In general, there were no serious adverse events during the course of this study. According to the results and considering the pharmacokinetic parameters reflecting the amount of Atorvastatin and Ezetimibe absorbed bythe body and the speed...

Reinserción del tendón patelar mediante sutura con cinta de dacrón: estudio experimental en cadáveres / Patellar tendon reinsertion through suture with Dacron band: experimental study in cadavers

Se realizó un estudio experimental en cadáveres humanos, en el que se incluyeron 16 rodillas, a las que se les practicó un corte nítido, completo sobre el tendón patelar del polo inferior de la patela. A ocho rodillas se les realizó una reconstrucción del tendón, reinsertándolo a través de tres túneles en la patela utilizando alambre y protegiéndolo con un cerclaje anclado a la tuberosidad anterior. A las ocho rodillas restantes también se les reinsertó el tendón patelar a través de tres túneles en la patela, utilizando solamente una cinta de dacrón. La cinta de dacrón es una sutura sintética que ofrece gran resistencia a la tracción y se usa tradicionalmente para la incompetencia cervical durante el embarazo. En Ortopedia se ha utilizado con buenos resultados en el tratamiento de las luxaciones acromio-claviculares. se realizaron pruebas de resistencia de los materiales en los tendones reparados, utilizando una máquina de ensayos universal Instrom 5586; donde se encontró que tanto la reinserción con alambre mas cerclaje de protección y la reinserción con cinta de dacrón, ofrecen resistencias similares; siendo ligeramente superior la resistencia del alambre. La reinserción del tendón patelar con cinta de dacrón resulta ser una herramienta adicional para el tratamiento de estas lesiones.

Evidence for involvement of c-Src in the anti-apoptotic action of nitric oxide in serum-deprived RINm5F cells.

The mechanism by which nitric oxide (NO) protects from apoptosis is a matter of debate. We have shown previously that phosphorylation of tyrosine residues participates in the protection from apoptosis in insulin-producing RINm5F cells (Inorg. Chem. Commun. 3 (2000) 32). Since NO has been reported to activate the tyrosine kinase c-Src and this kinase is involved in the activation of protein kinase G (PKG) in some cell systems, we aimed at studying the contribution of c-Src and PKG systems in anti-apoptotic actions of NO in serum-deprived RINm5F cells. Here we report that exposure of serum-deprived cells to 10 microM DETA/NO results in protection from degradation of the anti-apoptotic protein Bcl-2, together with a reduction of cytochrome c release from mitochondria and caspase-3 inhibition. Studies with the inhibitors ODQ and KT-5823 revealed that these actions are dependent on both activation of guanylate cyclase and PKG. DETA/NO was also able to induce autophosphorylation and activation c-Src protein both in vivo and in vitro and active c-Src was able to induce tyrosine phosphorylation of Bcl-2 in vitro. The c-Src kinase inhibitor PP1 abrogated the actions of DETA/NO on cGMP formation, PKG activation, caspase activation, cytochrome c release from mitochondria, and Bcl-2 phosphorylation and degradation in serum-deprived cells. We thus propose that activation of c-Src is an early step in the chain of events that signal cGMP-dependent anti-apoptotic actions of NO in mitocohondria.

Sodium nitroprusside-induced mitochondrial apoptotic events in insulin-secreting RINm5F cells are associated with MAP kinases activation.

Exposure of insulin-secreting RINm5F cells to the chemical nitric oxide donor sodium nitroprusside (SNP) resulted in apoptotic cell death, as detected by cytochrome c release from mitochondria and caspase 3 activation. SNP exposure also leads to phosphorylation and activation of enzymes involved in cellular response to stress such as signal-regulated kinase 2 (ERK2) and c-Jun NH(2)-terminal kinase 46 (JNK46). Both cytochrome c release and caspase 3 activation were abrogated in cells exposed to MEK and p38 inhibitors. Treatment of cells with the NO donors SNP, DETA-NO, GEA 5024, and SNAP resulted in phosphorylation of the antiapoptotic protein Bcl-2, which was resistant to blockade of MEK, p38, and JNK pathways and sensitive to phosphoinositide 3-kinase (PI3K) inhibition. In addition, transient transfection of cells with the wild-type PI3K gamma gene mimics the increased rate of Bcl-2 phosphorylation detected in NO-treated cells. The generation of phosphoinositides seems to participate in the process since Bcl-2 phosphorylation was not observed in cells overexpressing lipid-kinase-deficient PI3Kgamma. The potential of SNP toxicity directly from NO was supported by our finding that the NO scavenger carboxy-PTIO prevented cell death. We found no evidence to support the contention that oxygen radicals generated during cellular SNP metabolism mediate cell toxicity in RINm5F cells, since neither addition of catalase/superoxide dismutase nor transfection with superoxide dismutase prevented SNP-induced cell death. Thus, we propose that exposure to apoptotic concentrations of NO triggers ERK- and p38-dependent cytochrome c release, caspase 3 activation, and PI3K-dependent Bcl-2 phosphorylation.

[Giant inguinoscrotal bladder hernia]. / Hernia vesical inguinoescrotal gigante.

Inguinoscrotal bladder hernia occur in 0.4 to 3% of general poblation, though massive hernia are much rare. We present a new case of a giant inguinoscrotal bladder hernia, which was solved by surgery. It includes a clinical, diagnostic and therapeutic aspects, and a review of the relative literature.

Hernia vesical inguinoescrotal gigante / Giant inguinoscrotal bladder hernia

La hernia vesical inguinoescrotal acontece con una frecuencia de 0,4-3 por ciento, aunque la hernia vesical masiva sí es una entidad muy rara.Presentamos un caso de hernia vesical inguinoescrotal gigante que fue resuelto mediante tratamiento quirúrgico.Se realiza una revisión de los aspectos clínicos, diagnósticos y terapéuticos, y una revisión de la literatura al respecto. (AU)

The Village AIDS Day Treatment Program: a model of interdisciplinary and interdependent care.

This article describes the Village AIDS Day Treatment Program, a program for people living with HIV/AIDS that provides health care by using a full range of interdependent services. Opened in 1988, this program was the first of its kind in the country. It has provided leadership in developing a model of care that addresses the full spectrum of health care--promotion, prevention, maintenance, and treatment. Along with describing the program and its services, this article includes the program's history and its influencing philosophies.

[Bladder leiomyoma: review of the literature and report of 3 clinical cases]. / Leiomioma vesical: revisión de la literatura y presentación de tres casos clínicos.

Presentation of three cases of bladder leiomyoma in women. All cases were characterized for the unspecific clinical presentation and a difficult pre-operative diagnosis, where ultrasound, cystoscopies, CAT and PAAF were used as complementary methods. The certainty diagnosis was only obtained after the histological study of the surgical piece. Treatment was in all three cases surgical, and the pathoanatomical diagnosis was bladder leiomyoma.

Transient nonketotic hyperglycinaemia: ultrasound, CT and MRI: case report.

We report a case of transient nonketotic hyperglycinaemia in which radiography correlated closely with clinical and biochemical findings. Only 5 patients have been previously described with this transient from of nonketotic hyperglycinaemia. Among the radiographic findings, thinning of the corpus callosum is the most characteristic.

[Retrocaval ureter: report of a case]. / Ureter retrocavo: aportación de un caso.

OBJECTIVES: An additional case of retrocaval ureter is described, with special reference to the diagnosis and treatment of this uncommon condition. METHODS/RESULTS: We report a case of retrocaval ureter in a patient who had consulted for urological infection. Patient data and clinical history are presented and discussed. CONCLUSIONS: The clinical and pathological significance of retrocval ureter depend on the degree of urinary flow obstruction and the associated complications. CT with iv contrast medium is useful in confirming the diagnosis in most of the cases. When indicated, treatment by surgery and urinary tract maneuvers generally achieve good results.

[Non-ketotic hyperglycinemia. Transient neonatal form]. / Hiperglicinemia no cetósica. Forma neonatal transitoria.

We report a patient with neonatal epilepsy, with no pattern of burst-suppression, secondary to the transient form of nonketotic hyperglycinemia. Biochemical normalization at two weeks of age was followed by a good clinical evolution and neurological normality at one year of age. The patient showed markedly retarded myelination and microcysts in the frontal white matter, both transitory and with subsequent neuroradiological normalization. Only five patients have been previously described with this clinical variant, there being suspicion of a glycine cleavage system deficiency due to neonatal enzymatic immaturity.

[Moderate hypercholesterolemia in children. An index of familial pathology?]. / Hipercolesterolemia moderada en niños. Indice de patología familiar?

Out of 44 children (with 200 mg/dl cholesterol) 22, with constantly high levels of cholesterol were studied. All belong to a children population from Madrid which 95 percentile for cholesterol was 204 mg/dl. Fifty nine subjects, first degree relatives of these 22 children (17 families) plus probands were studied to determine if moderately elevated cholesterol levels during infancy are related to any form of familial lipidic disorder. Serum lipidic levels, anthropometric measurements, dietary habits a history of atherosclerotic cardiovascular disease (ACVD), were evaluated in all these 81 individuals. Hypercholesterolemia was encountered in 13 of the 59 non probands and high triglyceride levels in 6 people. More than one member of the family was to have some form of lipidic disorder in 12 of 17 families (71%) and in 10 the metabolic abnormality was of a type associated with a higher risk to suffer ACVD. Five families had a combined hyperlipidemia of the multiple lipoproteinemic (4 familiar heterozygotic hypercholesterolemia and one hyperlipidemia with a double phenotype II B and V). All family members were apparently healthy and had no knowledge of their underlying lipidic abnormality. In this group of families antecedents of morbi-mortality because of atherosclerosis were more frequent that in group control families. Authors conclude that a moderately elevated serum cholesterol level during infancy may be a marker for various familiar lipidic disorders. Detection in infantile population of serum cholesterol levels 200 mg/dl should prompt us to perform a more complete lipidic evaluation both in children as well as in their families.