Historical epidemiology of hepatitis C virus in select countries-volume 4.

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Strategies for the management of haemorrhage following pelvic fractures and associated trauma-induced coagulopathy.

Exsanguination is the second most common cause of death in patients who suffer severe trauma. The management of haemodynamically unstable high-energy pelvic injuries remains controversial, as there are no universally accepted guidelines to direct surgeons on the ideal use of pelvic packing or early angio-embolisation. Additionally, the optimal resuscitation strategy, which prevents or halts the progression of the trauma-induced coagulopathy, remains unknown. Although early and aggressive use of blood products in these patients appears to improve survival, over-enthusiastic resuscitative measures may not be the safest strategy. This paper provides an overview of the classification of pelvic injuries and the current evidence on best-practice management of high-energy pelvic fractures, including resuscitation, transfusion of blood components, monitoring of coagulopathy, and procedural interventions including pre-peritoneal pelvic packing, external fixation and angiographic embolisation.

Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder.

Biotin is the prosthetic group of carboxylases that have important roles in the metabolism of glucose, fatty acids and amino acids. Biotinidase has a key role in the reutilization of the biotin, catalyzing the hydrolysis of biocytin (ε-N-biotinyl-l-lysine) and biocytin-containing peptides derived from carboxylase turnover, thus contributing substantially to the bioavailability of this vitamin. Deficient activity of biotinidase causes late-onset multiple carboxylase in humans, whose pathogenic mechanisms are poorly understood. Here we show that a knock-out biotinidase-deficient mouse from a C57BL/6 background that was fed a low biotin diet develops severe ATP deficit with activation of the energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK), inhibition of the signaling protein mTOR, driver of protein synthesis and growth, and affecting the expression of central-carbon metabolism genes. In addition, sensitivity to insulin is augmented. These changes are similar to those observed in nutritionally biotin-starved rats. These findings further our understanding of the pathogenesis of human biotinidase deficiency.

Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).

BACKGROUND/AIM: Biotin affects the genetic expression of several glucose metabolism enzymes, besides being a cofactor of carboxylases. To explore how extensively biotin affects the expression of carbon metabolism genes, we studied the effects of biotin starvation and replenishment in 3 distantly related eukaryotes: yeast Saccharomyces cerevisiae, nematode Caenorhabditis elegans and rat Rattus norvegicus. METHODS: Biotin starvation was produced in Wistar rats, in C. elegans N2 and S. cerevisiae W303A fed with abundant glucose. High-density oligonucleotide microarrays were used to find gene expression changes. Glucose consumption, lactate and ethanol were measured by conventional tests. RESULTS: In spite of abundant glucose provision, the expression of fatty oxidation and gluconeogenic genes was augmented, and the transcripts for glucose utilization and lipogenesis were diminished in biotin starvation. These results were associated with diminished glucose consumption and glycolysis products (lactate and ethanol in yeast), which was consistent across 3 very different eukaryotes. CONCLUSION: The results point toward a strongly selected role of biotin in the control of carbon metabolism, and in adaptations to variable availability of carbon, conceivably mediated by signal transduction including soluble guanylate cyclase, cGMP and a cGMP-dependent protein kinase (PKG) and/or biotin-dependent processes.

Penile prosthesis in the organ transplant recipient.

OBJECTIVES: To determine whether pelvic organ transplant recipients are at a higher risk of developing complications after placement of a penile prosthesis relative to those receiving a penile prosthesis who did not undergo pelvic organ transplantation. METHODS: Two hundred eleven men underwent placement of a penile prosthesis by a single urologist at our institution between July 1994 and March 2000. Of these, 46 patients had undergone pelvic organ transplantation before placement of the penile prosthesis. The average time from transplantation was 43 months. The average follow-up after prosthesis placement was 23 months. These patients were monitored for various complications, including infection, malfunction, autoinflation, and injury to the prosthesis. They were compared with a cohort of men who had had a prosthesis placed but had not received pelvic organ transplantation. RESULTS: The overall complication rate was significantly higher in the transplant patients (22%) than in the nontransplant patients (7.9%) receiving prostheses (P <0.01). Infection was seen in 2 transplant patients (4.3%) and in 7 nontransplant patients (4.2%) (P <1). Malfunction occurred in 4 of the transplant patients (8.7%) and 6 of the nontransplant patients (3.6%) (P <0.2). In those patients with a prosthesis malfunction, 9 of 10 involved a three-piece prosthesis. All four malfunctions in the transplant group occurred in three-piece prostheses. The difference in the rate of malfunction was statistically significant (P <0.001) when comparing the three-piece prosthesis in the transplant and nontransplant patients (P <0.001). Surgical injury to the retroperitoneal reservoir occurred in 4 transplant patients (8.7%) (all with three-piece prostheses) and in none of the nontransplant patients (P <0.001). CONCLUSIONS: The risk of infection after insertion of penile prostheses in patients with pelvic organ transplantation was similar to that in nontransplant patients. The risk of malfunction and injury to the prosthesis (three-piece) was higher in transplant patients. The overall complication rate was significantly higher in patients after transplantation and can be attributed to the reservoir complications related to three-piece prostheses. In patients with a prosthesis that did not have a retroperitoneal reservoir, no significant difference in the overall complication rate was observed. Pelvic organ transplant recipients in whom traditional conservative therapy for erectile dysfunction fails should be considered candidates for penile prosthesis placement. However, three-piece prostheses should be avoided, as these patients are best served with prostheses that do not require a retroperitoneal reservoir.

Future concepts in the medical therapy of benign prostatic hyperplasia.

The standard medical therapy for symptomatic benign prostatic hyperplasia is still alpha-blockers and 5alpha-reductase inhibitors. Ongoing studies demonstrate the long-term safety and efficacy of these two classes of therapeutic approaches. Although there have been no new Food and Drug Administration approved medical therapies for the treatment of benign prostatic hyperplasia over the past year, interest in and the use of phytotherapeutic agents continues to increase. In this review, we will discuss the developments that have occurred over the past year in the medical management of benign prostatic hyperplasia. In addition, we present ongoing efforts at our center to obtain a better understanding of and manipulate the apoptotic pathway as it pertains to the pathophysiology of benign prostatic hyperplasia.

Open laparoscopic access using a radially dilating trocar: experience and indications in 50 consecutive cases.

BACKGROUND: Laparoscopy can be performed using needle access for initial insufflation or open access. PATIENTS AND METHODS: A technique for open laparoscopic access to the abdomen using a radially dilating cannula was used in 52 operations in 50 patients. Indications included age <2 years, severe kyphosis, and creation of an umbilical stoma. RESULTS: There was one case of minor leakage of carbon dioxide that did not affect the procedure being performed. There were two cases of preperitoneal placement, which were recognized immediately; in both, peritoneal access was easily obtained. CONCLUSION: Open laparoscopic access is safely and easily performed with a radially dilating trocar. This is the preferred technique at our institution for patients who meet the criteria for open access.

Structure and function of the class C tetracycline/H+ antiporter: three independent groups of phenotypes are conferred by TetA (C).

The class C tetracycline/H+ antiporter, TetA(C), confers nine distinct phenotypes in Escherichia coli: resistance to tetracycline, reduced culture density at stationary phase (growth yield), increased supercoiling of plasmid DNA, delayed growth in succinate minimal medium, complementation of potassium uptake defects, increased susceptibility to cadmium, increased susceptibility to fusaric acid, increased susceptibility to bleomycin and increased susceptibility to several classes of cationic aminoglycoside antibiotics. These nine phenotypes were resolved into three 'linkage' groups based on their patterns of suppression by mutations of the tetA(C) gene of plasmid pBR322. Group I includes resistance to tetracycline, increased susceptibility to cadmium and reduced growth yield. Group II includes delayed growth in succinate minimal medium and complementation of potassium uptake defects. Group III includes increased supercoiling of plasmid DNA and increased susceptibilities to fusaric acid, bleomycin and cationic aminoglycosides. Phenotypes of Groups II and III, but not Group I, also were conferred by a chimeric gene encoding a fusion between the N-terminal 34 residues of TetA(C) and the C-terminal 429 residues of a structurally-similar protein, the E. coli galactose/H+ symporter, GalP. In contrast, none of these phenotypes was conferred by a chimeric gene encoding a fusion between the N-terminal 34 residues of TetA(C) and a structurally-dissimilar protein, TEM beta-lactamase. These results demonstrate that the three groups of linked phenotypes are dependent on different elements of the TetA(C) amino acid sequence, implying that TetA(C) confers these phenotypes by at least three independent mechanisms.

Growth and nutrition patterns of infants associated with a nutrition education and supplementation programme in Gaza, 1987-92.

Since 1986, the 28 government community health centres providing primary care in Gaza have paid special attention to growth monitoring, nutrition education, and routine vitamin and iron supplementation in infancy. In 1987-88, 1989 and 1992, respectively, the nursing staff in five of these centres monitored the growth and feeding patterns of 2222, 1899, and 1012 children aged up to 15 months. The growth measures of children aged up to 6 months were similar to standard growth charts, but subsequently deficiencies developed in the study children. There were no differences between the patterns for males and females. Infants from upper socioeconomic categories had growth patterns that were closest to the norm, but this was associated with feeding and supplementation differences. There was improvement in the growth and feeding patterns of the 1989 and 1990-92 birth cohorts compared with the 1987-88 group and with the standard. Feeding patterns showed high levels of compliance with nutrition guidance. Growth monitoring, staff and maternal education, and supplementation with vitamins and, especially, iron were associated with marked improvements in feeding patterns and the growth status of children aged 3-15 months.

La ruptura artificial de las membranas y su relacion con la evolucion del parto / The rupture artificial of the membrane and your relation with the evolution and delivery

Se realiza el siguiente trabajo con el fin de conocer la frecuencia del uso de la ruptura artificial de membranas. la incidencia en cada edad y paridad y sobre los resultados obtenidos en cuanto a su utilizacion y relacion con la evolucion cuantitativa y cualitativa del trabajo de parto. Para ello se utilizaron las historias clinicas de los meses de abril a junio del año 1992, las cuales tenian en comun la utilizacion de la amniotomia, independientemente de la forma de culmincacion del parto. Una vez revisadas las 292 historias clinicas seleccionadas, observamos que en el (69.8 por ciento), de estas pacientes se realizo la amniotomia, observando que el mayor porcentaje corresponde a paciente multiparas y que independientemente de la paridad la RAM se realizo en las primeras dos horas post-internacion. El tiempo de lactancia en todas las pacientes independientemente de la paridad, ocurrio en la mayoria de los casos entre 1ra. y 4ta. horas post-amniotomia. La terminacion de los partos en un (90 por ciento) fue normal, se realizo tambien la observacion sobre las caracteristicas del liquido amniotico encontrada en cada caso, teniendo en cuenta que todos los embarazos fueron a termino, el liquido amniotico encontrado fue de caracteristicas grumoso claro y francamente grumoso, coorespondiendo un (20 por ciento) a la caracteristica meconial, se correlaciono esta caracteristica con la frecuencia cardiaca fetal (FCF) y luego con apgar al minuto, encontrando la relacion Meconio-Apgar solo en un (6 por ciento) de las pacientes con esta caracteristica, con Apagr menor o igual a 6 lo que corresponde al (1 por ciento) del total de la muestra, tambien observamos que una mayoria de pacientes a las cuales se les practico el procedimiento, no necesitan conduccion oxitocixa acompanante (63 por ciento). De las pacientes que necesitaron conduccion oxitocica en un (50 por ciento) acabaron en cesarea, cuya razon en su mayoria correspondio a una distocia de variedad de posicion, entre las cuales se destaca la OIDP. La FCF luego de la amniotomia tuvo una variacion de un (11//, 2/3) de esta variacion correspondio a una bradicardia, la cual al momento de nacimiento no se reflejo en un Apgar bajo en la mayoria de los casos