Objective To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA). Study design A ...retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford. Results Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 μmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 μmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 μmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning. Conclusions LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Keratin 8 and 18 (K8/K18) mutations are found in patients with cryptogenic cirrhosis, but the role of keratin mutations in noncryptogenic cirrhosis and the incidence of keratin mutations in the ...general population are not known. We screened for K8/K18 mutations in genomic DNA isolated from 314 liver explants of patients who primarily had noncryptogenic cirrhosis, and from 349 blood bank volunteers. Seven unique K8/K18 mutations were found in 11 independent patients with biliary atresia, hepatitis B/C, alcohol, primary biliary cirrhosis, and fulminant hepatitis. Seven of the 11 patients had mutations previously described in patients with cryptogenic cirrhosis: K8 Tyr-53 → His, K8 Gly-61 → Cys, and K18 His-127 → Leu. The four remaining patients had mutations at one K8 and three other K18 new sites. Of the 349 blood bank control samples, only one contained the Tyr-53 → His and one the Gly-61 → Cys K8 mutations (P < 0.004 when comparing cirrhosis versus control groups). Two additional mutations were found in both the liver disease and blood bank groups and, hence, likely represent polymorphisms. Livers with keratin mutations had cytoplasmic filamentous deposits that were less frequent in livers without the mutations (P = 0.03). Therefore, K8/K18 are likely susceptibility genes for developing cryptogenic and noncryptogenic forms of liver disease.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
► Hepatocytes from Neotropical fish Prochilodus lineatus were isolated with dispase. ► Cyanotoxin cylindrospermopsin CYN reduced hepatocytes viability at low concentrations. ► Multixenobiotic ...resistance mechanism (MXR) was impaired by CYN. ► CYN increased ROS production and lipid peroxidation in hepatocytes. ► Protein and DNA damages as well as GSH/GSSG ratio were not involved in CYN toxicity.
Cylindrospermopsin is a potent toxicant for eukaryotic cells produced by several cyanobacteria. Recently, primary hepatocyte cultures of Neotropical fish have been established, demonstrating to be a quite efficient in vitro model for cellular toxicology studies. In the current study, a protocol for culture of Prochilodus lineatus hepatocytes was established and utilized to investigate the cellular responses to purified cylindrospermopsin exposure. Hepatocytes were successfully dissociated with dispase, resulting in a cell yield of 6.36×107cellsg−1 of liver, viability of 97% and attachment on uncoated culture flasks. For investigation of cylindrospermopsin effects, hepatocytes were dissociated, cultured during 96h and exposed to three concentrations of the toxin (0.1, 1.0 or 10μgl−1) for 72h. Cylindrospermopsin exposure significantly decreased cell viability (0.1 and 1μgl−1) and multixenobiotic resistance mechanism, MXR (all exposed groups), but increased reactive oxygen/nitrogen species levels (all exposed groups) and lipid peroxidation (10μgl−1). On the other hand no significant alterations were observed for other biochemical biomarkers as 2GSH/GSSG ratio, protein carbonyl levels and DNA strand breaks or glutathione S-transferase and glucose 6-phosphate dehydrogenase activities. In conclusion, hepatocytes might be made sensitive to cylindrospermopsin, at least in part, due to reduction of xenobiotics and endobiotics efflux capacity by MXR. Additionally, the toxin exposure suggests important issues regarding hepatocytes survival at the lowest cylindrospermopsin concentrations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study investigated the effects of different doses of 17-β-estradiol (E
2) in
Rhamdia quelen. Groups of males exposed to different doses of E
2 (0.1
mg
kg
−
1, 1
mg
kg
−
1 and 10
mg
kg
−
1) were ...compared with non-exposed male and female fish groups. Among the considered biomarkers, no significant differences were observed for micronuclei test, reduced glutathione concentration and lipid peroxidation. All E
2-treated individuals had decreased glutathione
S-transferase activity. Increased catalase and superoxide dismutase activities, increased vitellogenin expression and decreased metallothionein concentration were observed in males treated with the highest dose. Liver of all test groups showed necrotic areas, but cytoplasm vacuolization was again found only in the individuals exposed to highest dose. E
2 causes deleterious hepatic effects to
R. quelen, and vitellogenin expression, catalase and superoxide dismutase activity and metallothionein concentration represent appropriate biomarkers for studying E
2 effects. Additionally, the response of some biomarkers was similar in males exposed to E
2 and unexposed females, and therefore exposure to endocrine disruptors may cause consequences for fish populations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background It was previously estimated that 234·2 million operations were performed worldwide in 2004. The association between surgical rates and population health outcomes is not clear. We ...re-estimated global surgical volume to track changes over time and assess rates associated with healthy populations. Methods We gathered demographic, health, and economic data for 194 WHO member states. Surgical volumes were obtained from published studies and other reports from 2005 onwards. We estimated rates of surgery for all countries without available data based on health expenditure in 2012 and assessed the proportion of surgery comprised by caesarean delivery. The rate of surgery was plotted against life expectancy to describe the association between surgical care and this health indicator. Findings We identified 66 countries reporting surgical data between 2005 and 2013. We estimate that 312·9 million operations (95% CI 266·2–359·5) took place in 2012—a 33·6% increase over 8 years; the largest proportional increase occurred in countries spending US$400 or less per capita on health care. Caesarean delivery comprised 29·8% (5·8 million operations) of the total surgical volume in poor health expenditure countries compared with 10·8% (7·8 million operations) in low health expenditure countries and 2·7% (5·1 million operations) in high health expenditure countries. We noted a correlation between increased life expectancy and increased surgical rates up to 1533 operations per 100 000 people, with significant but less dramatic improvement above this rate. Interpretation Surgical volume is large and continues to grow in all economic environments. A single procedure—caesarean delivery—comprised almost a third of surgical volume in the most resource-limited settings. Surgical care is an essential part of health care and is associated with increased life expectancy, yet many low-income countries fail to achieve basic levels of service. Improvements in capacity and delivery of surgical services must be a major component of health system strengthening. Funding None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
La leishmaniosis es una enfermedad causada por parásitos protozoarios del género Leishmania y transmitida a mamíferos mediante la picadura de insectos dípteros hematófagos del género Lutzomyia en el ...nuevo mundo. Los caninos son susceptibles de adquirir la forma visceral y la forma cutánea de la enfermedad. Los métodos de diagnóstico incluyen observación directa del parásito por microscopía óptica, serología o técnicas de biología molecular en muestras de perros con signos clínicos evidentes y/o sospecha clínica. En este estudio se evaluó la utilidad de una reacción en cadena de la polimerasa anidada (PCRn) para el diagnóstico de dicha patología en perros. Se analizaron 18 muestras de sangre entera anticoagulada con EDTA de perros de la ciudad de Corrientes con sospecha clínica de padecer leishmaniosis. A partir de las mismas, se extrajo ácido desoxiribonucleico (ADN) y se realizaron dos rondas de amplificación sucesivas de una secuencia que codifica para la subunidad pequeña de ARN ribosomal. Los resultados obtenidos de las PCR anidadas fueron comparados con los resultados obtenidos a partir del método parasitológico directo considerado como gold standard. La técnica aplicada mostró sensibilidad del 100%, especificidad del 75%, valor predictivo positivo del 67% y valor predictivo negativo del 100% lo que la convierte en una herramienta útil para el diagnóstico de leishmaniosis canina.
IMPORTANCE: Based on older analyses, the World Health Organization (WHO) recommends that cesarean delivery rates should not exceed 10 to 15 per 100 live births to optimize maternal and neonatal ...outcomes. OBJECTIVES: To estimate the contemporary relationship between national levels of cesarean delivery and maternal and neonatal mortality. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, ecological study estimating annual cesarean delivery rates from data collected during 2005 to 2012 for all 194 WHO member states. The year of analysis was 2012. Cesarean delivery rates were available for 54 countries for 2012. For the 118 countries for which 2012 data were not available, the 2012 cesarean delivery rate was imputed from other years. For the 22 countries for which no cesarean rate data were available, the rate was imputed from total health expenditure per capita, fertility rate, life expectancy, percent of urban population, and geographic region. EXPOSURES: Cesarean delivery rate. MAIN OUTCOMES AND MEASURES: The relationship between population-level cesarean delivery rate and maternal mortality ratios (maternal death from pregnancy related causes during pregnancy or up to 42 days postpartum per 100 000 live births) or neonatal mortality rates (neonatal mortality before age 28 days per 1000 live births). RESULTS: The estimated number of cesarean deliveries in 2012 was 22.9 million (95% CI, 22.5 million to 23.2 million). At a country-level, cesarean delivery rate estimates up to 19.1 per 100 live births (95% CI, 16.3 to 21.9) and 19.4 per 100 live births (95% CI, 18.6 to 20.3) were inversely correlated with maternal mortality ratio (adjusted slope coefficient, −10.1; 95% CI, −16.8 to −3.4; P = .003) and neonatal mortality rate (adjusted slope coefficient, −0.8; 95% CI, −1.1 to −0.5; P < .001), respectively (adjusted for total health expenditure per capita, population, percent of urban population, fertility rate, and region). Higher cesarean delivery rates were not correlated with maternal or neonatal mortality at a country level. A sensitivity analysis including only 76 countries with the highest-quality cesarean delivery rate information had a similar result: cesarean delivery rates greater than 6.9 to 20.1 per 100 live births were inversely correlated with the maternal mortality ratio (slope coefficient, −21.3; 95% CI, −32.2 to −10.5, P < .001). Cesarean delivery rates of 12.6 to 24.0 per 100 live births were inversely correlated with neonatal mortality (slope coefficient, −1.4; 95% CI, −2.3 to −0.4; P = .004). CONCLUSIONS AND RELEVANCE: National cesarean delivery rates of up to approximately 19 per 100 live births were associated with lower maternal or neonatal mortality among WHO member states. Previously recommended national target rates for cesarean deliveries may be too low.
To estimate global surgical volume in 2012 and compare it with estimates from 2004.
For the 194 Member States of the World Health Organization, we searched PubMed for studies and contacted key ...informants for reports on surgical volumes between 2005 and 2012. We obtained data on population and total health expenditure per capita for 2012 and categorized Member States as very-low, low, middle and high expenditure. Data on caesarean delivery were obtained from validated statistical reports. For Member States without recorded surgical data, we estimated volumes by multiple imputation using data on total health expenditure. We estimated caesarean deliveries as a proportion of all surgery.
We identified 66 Member States reporting surgical data. We estimated that 312.9 million operations (95% confidence interval, CI: 266.2-359.5) took place in 2012, an increase from the 2004 estimate of 226.4 million operations. Only 6.3% (95% CI: 1.7-22.9) and 23.1% (95% CI: 14.8-36.7) of operations took place in very-low- and low-expenditure Member States representing 36.8% (2573 million people) and 34.2% (2393 million people) of the global population of 7001 million people, respectively. Caesarean deliveries comprised 29.6% (5.8/19.6 million operations; 95% CI: 9.7-91.7) of the total surgical volume in very-low-expenditure Member States, but only 2.7% (5.1/187.0 million operations; 95% CI: 2.2-3.4) in high-expenditure Member States.
Surgical volume is large and growing, with caesarean delivery comprising nearly a third of operations in most resource-poor settings. Nonetheless, there remains disparity in the provision of surgical services globally.
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CEKLJ, DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract Background The global volume of surgery in 2012 is estimated at 312·9 million operations per year, but rates of surgery vary substantially. Maternal health advocates proposed minimum ...caesarean delivery rates for benchmarking and to improve perinatal outcomes; however, this has not been done for surgery because the association between rates of surgical care provision as a whole and population health outcomes have not been well described. We use available data to estimate minimum rates of surgery that are associated with important health indicators. Methods We defined surgical operations as procedures done in operating theatres that need general or regional anaesthesia or profound sedation to control pain. We used four strategies to identify rates of surgery based on estimated rates of surgery per country for 2012 associated with life expectancy of 74–75 years; estimated rates of surgery associated with a maternal mortality ratio of less than or equal to 100 per 100 000 live births; estimated minimum need for surgery in the 21 Global Burden of Disease (GBD) regions based on the prevalence of disorders; and surgical rates from the so-called 4C countries (Chile, China, Costa Rica, and Cuba) identified in The Lancet Commission on Global Surgery as exemplary for their achievement of high health status, despite resource limitations. Findings Based on 2012 national surgical rates, countries with reported life expectancy of 74–75 years (n=17) had a median surgical rate of 4392 (IQR 2897–4873) operations per 100 000 population annually. The median surgical rate associated with maternal mortality ratio lower than 100 (n=109) is 5028 (IQR 4139–6778) operations per 100 000 population annually. The median surgical rate estimated for all 21 GBD regions was 4669 (IQR 4339–5291) operations per 100 000 population annually. The 4C countries had a mean surgical rate of 4344 (95% CI 2620–6068) operations per 100 000 population annually. 13 of the 21 GBD regions, accounting for 78% of the world's population, do not achieve the lowest end of the surgical rate range. Interpretation We identified a surprisingly narrow range of surgical rates associated with important health indicators. This target range can be used for benchmarking of surgical services, and as part of a policy aimed at strengthening health-care systems and surgical capacity. Funding None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Recent work has indicated an increase in surgical services, especially in resource poor settings. However, the rate of growth is poorly understood and likely insufficient to meet ...public health needs. We previously identified a range of 4344 to 5028 operations per 100 000 population annually to be related to desirable health outcomes. From this and other evidence, the Lancet Commission on Global Surgery recommends a minimum rate of 5000 operations per 100 000 population. We evaluate rates of growth in surgery and estimate the time it will take to reach this minimum surgical rate threshold. Methods We aggregated 2004 and 2012 country-level surgical rate estimates into the 21 Global Burden of Disease (GBD) regions. We calculated mean rates of surgery proportional to population size and estimate rate of growth between these years. We then extrapolated the time it will take to reach a surgical rate of 5000 operations per 100 000 population based on linear rates of change. Findings All but two regions (central Europe and southern Latin America) experienced growth in their surgical rates during the past 8 years; the fastest growth occurred in regions with the lowest surgical rates. 14 regions representing 79% of the world's population (5·5 billion people) did not meet the recommended surgical rate threshold in 2012. If surgical capacity grows at current rates, seven regions (central sub-Saharan Africa, east Asia, eastern sub-Saharan Africa, north Africa and middle east, south Asia, southeast Asia, and western sub-Saharan Africa) will not meet the recommended surgical rate threshold by 2035; Eastern Sub-Saharan Africa will not reach this level until 2124. Interpretation The rates of growth in surgical service delivery are exceedingly variable, but the largest growth rates were noted in the poorest regions. Although this study does not address the quality of care, and rates of surgery are unlikely to change linearly, this exercise is useful to project how many years it could take regions to reach specific surgical rates. At current rates of growth, 4·9 billion people (70% of the world's population) will still be living in countries below the minimum recommended rate of surgery in 2035. A strategy for strengthening surgical capacity is essential if these targets are to be met as part of integrated health system development. Funding None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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