Hepatitis C and human immunodeficiency virus infections in injecting drug users in drug treatment centers in Vietnam

Background. Injecting drug users (IDUs) are at risk of infection with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Independently, each of these viruses is a serious threat to health, with HIV ravaging the body’s immune system, and HCV causing cirrhosis, liver cancer and liver failure. Co-infection with HIV/HCV weakens the response to antiretroviral therapy in HIV patients. IDUs with HIV/HCV co-infection are at a 20 times higher risk of having liver-related morbidity and mortality than IDUs with HIV alone. In Vietnam, studies to ascertain the prevalence of HIV have found high rates, but little is known about their HCV status. ^ Purpose. To measure the prevalence of HCV and HIV infection and identify factors associated with these viruses among IDUs at drug treatment centers in northern Vietnam. ^ Methods. A cross-sectional study was conducted from November 2007 to February 2008 with 455 injecting drug users aged 18 to 39 years, admitted no more than two months earlier to one of four treatment centers in Northern Vietnam (Hatay Province) (response rate=95%). Participants, all of whom had completed detoxification and provided informed consent, completed a risk assessment questionnaire and had their blood drawn to test for the presence of antibody-HCV and antibody-HIV with enzyme immuno assays. Univariate and multivariable logistic regression models were utilized to explore the strength of association using HIV, HCV infections and HIV/HCV co-infection as outcomes and demographic characteristics, drug use and sexual behaviors as factors associated with these outcomes. Unadjusted and adjusted odds ratios and 95% confidence intervals were calculated. ^ Results. Among all IDU study participants, the prevalence of HCV alone was 76.9%, HIV alone was 19.8%. The prevalence of HIV/HCV co-infection was 92.2% of HIV-positive and 23.7% of HCV-positive respondents. No sexual risk behaviors for lifetime, six months or 30 days prior to admission were significantly associated with HCV or HIV infection among these IDUs. Only duration of injection drug use was independently associated with HCV and HIV infection, respectively. Longer duration was associated with higher prevalence. Nevertheless, while HCV infection among IDUs who reported being in their first year of injecting drugs were lower than longer time injectors, their rates were still substantial, 67.5%. ^ Compared with either HCV mono-infection or HIV/HCV non-infection, HIV/HCV co-infection was associated with the length of drug injection history but was not associated with sexual behaviors. Higher education was associated with a lower prevalence of HIV/HCV co-infection. When compared with HIV/HCV non-infection, current marriage was associated with a lower prevalence of HIV/HCV co-infection. ^ Conclusions. HCV was prevalent among IDUs from 18 to 39 years old at four drug treatment centers in northern Vietnam. Co-infection with HCV was predominant among HIV-positive IDUs. HCV and HIV co-infection were closely associated with the length of injection drug history. Further research regarding HCV/HIV co-infection should include non-injecting drug users to assess the magnitude of sexual risk behaviors on HIV and HCV infection. (At these treatment centers non-IDUs constituted 10-20% of the population.) High prevalence of HCV prevalence among IDUs, especially among HIV-infected IDUs, suggests that drug treatment centers serving IDUs should include not only HIV prevention education but they should also include the prevention of viral hepatitis. In addition, IDUs who are HIV-positive need to be tested for HCV to receive the best course of therapy and achieve the best response to HIV treatment. These data also suggest that because many IDUs get infected with HCV in the first year of their injection drug career, and because they also engaged in high risk sexual behaviors, outreach programs should focus on harm reduction, safer drug use and sexual practices to prevent infection among drug users who have not yet begun injecting drugs and to prevent further spread of HCV, HIV and co-infection. ^

Exposure to nonsteroidal anti-inflammatory drugs and weight loss and hospitalization in non-small cell lung cancer patients

Background. Cancer cachexia is a common syndrome complex in cancer, occurring in nearly 80% of patients with advanced cancer and responsible for at least 20% of all cancer deaths. Cachexia is due to increased resting energy expenditure, increased production of inflammatory mediators, and changes in lipid and protein metabolism. Non-steroidal anti-inflammatory drugs (NSAIDs), by virtue of their anti-inflammatory properties, are possibly protective against cancer-related cachexia. Since cachexia is also associated with increased hospitalizations, this outcome may also show improvement with NSAID exposure. ^ Design. In this retrospective study, computerized records from 700 non-small cell lung cancer patients (NSCLC) were reviewed, and 487 (69.57%) were included in the final analyses. Exclusion criteria were severe chronic obstructive pulmonary disease, significant peripheral edema, class III or IV congestive heart failure, liver failure, other reasons for weight loss, or use of research or anabolic medications. Information on medication history, body weight and hospitalizations was collected from one year pre-diagnosis until three years post-diagnosis. Exposure to NSAIDs was defined if a patient had a history of being treated with NSAIDs for at least 50% of any given year in the observation period. We used t-test and chi-square tests for statistical analyses. ^ Results. Neither the proportion of patients with cachexia (p=0.27) nor the number of hospitalizations (p=0.74) differed among those with a history of NSAID use (n=92) and those without (n=395). ^ Conclusions. In this study, NSAID exposure was not significantly associated with weight loss or hospital admissions in patients with NSCLC. Further studies may be needed to confirm these observations.^

An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen

Nrf2, a member of the “cap ‘n collar” group of transcription factors, is important for protecting cells against oxidative damage. We investigated its role in the detoxification of acetaminophen [N-acetyl-p-aminophenol (APAP)]-induced hepatotoxicity. When Nrf2 knockout (Nrf2−/−) and wild-type mice were given APAP by i.p. injection, the Nrf2−/− mice were highly susceptible to APAP treatment. With doses of APAP that were tolerated by wild-type mice, the Nrf2−/− mice died of liver failure. When hepatic glutathione was depleted after a dose of 400 mg/kg of APAP, the wild-type mice were able to compensate and regain the normal glutathione level. In contrast, the glutathione level in the Nrf2−/− mice was not compensated and remained low. This was because of the decrease in the gene expression of gcsH and gcsL as well as gss in the livers of the Nrf2−/− mice. In addition, the expression of ugt1a6 and gstpi that detoxify APAP by conjugation was also decreased. This increased susceptibility of the Nrf2−/− mice to APAP, because of an impaired capacity to replenish their glutathione stores, compounded with a decreased detoxification capability, highlights the importance of Nrf2 in the regulation of glutathione synthesis and cellular detoxification processes.

Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.

beta-Oxidation of long-chain fatty acids provides the major source of energy in the heart. Defects in enzymes of the beta-oxidation pathway cause sudden, unexplained death in childhood, acute hepatic encephalopathy or liver failure, skeletal myopathy, and cardiomyopathy. Very-long-chain acyl-CoA dehydrogenase [VLCAD; very-long-chain-acyl-CoA:(acceptor) 2,3-oxidoreductase, EC 1.3.99.13] catalyzes the first step in beta-oxidation. We have isolated the human VLCAD cDNA and gene and determined the complete nucleotide sequences. Polymerase chain reaction amplification of VLCAD mRNA and genomic exons defined the molecular defects in two patients with VLCAD deficiency who presented with unexplained cardiac arrest and cardiomyopathy. In one, a homozygous mutation in the consensus dinucleotide of the donor splice site (g+1-->a) was associated with universal skipping of the prior exon (exon 11). The second patient was a compound heterozygote, with a missense mutation, C1837-->T, changing the arginine at residue 613 to tryptophan on one allele and a single base deletion at the intron-exon 6 boundary as the second mutation. This initial delineation of human mutations in VLCAD suggests that VLCAD deficiency reduces myocardial fatty acid beta-oxidation and energy production and is associated with cardiomyopathy and sudden death in childhood.

Insuficiência hepática aguda provocada por Amanita phalloides

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Biochemical correlates of cognition: exploring the relationships between blood, brain and behaviour

This multi-modal investigation aimed to refine analytic tools including proton magnetic resonance spectroscopy (1H-MRS) and fatty acid gas chromatography-mass spectrometry (GC-MS) analysis, for use with adult and paediatric populations, to investigate potential biochemical underpinnings of cognition (Chapter 1). Essential fatty acids (EFAs) are vital for the normal development and function of neural cells. There is increasing evidence of behavioural impairments arising from dietary deprivation of EFAs and their long-chain fatty acid metabolites (Chapter 2). Paediatric liver disease was used as a deficiency model to examine the relationships between EFA status and cognitive outcomes. Age-appropriate Wechsler assessments measured Full-scale IQ (FSIQ) and Information Processing Speed (IPS) in clinical and healthy cohorts; GC-MS quantified surrogate markers of EFA status in erythrocyte membranes; and 1H-MRS quantified neurometabolite markers of neuronal viability and function in cortical tissue (Chapter 3). Post-transplant children with early-onset liver disease demonstrated specific deficits in IPS compared to age-matched acute liver failure transplant patients and sibling controls, suggesting that the time-course of the illness is a key factor (Chapter 4). No signs of EFA deficiency were observed in the clinical cohort, suggesting that EFA metabolism was not significantly impacted by liver disease. A strong, negative correlation was observed between omega-6 fatty acids and FSIQ, independent of disease diagnosis (Chapter 5). In a study of healthy adults, effect sizes for the relationship between 1H-MRS- detectable neurometabolites and cognition fell within the range of previous work, but were not statistically significant. Based on these findings, recommendations are made emphasising the need for hypothesis-driven enquiry and greater subtlety of data analysis (Chapter 6). Consistency of metabolite values between paediatric clinical cohorts and controls indicate normal neurodevelopment, but the lack of normative, age-matched data makes it difficult to assess the true strength of liver disease-associated metabolite changes (Chapter 7). Converging methods offer a challenging but promising and novel approach to exploring brain-behaviour relationships from micro- to macroscopic levels of analysis (Chapter 8).

Utilização de mapas conceituais como ferramenta de ensino para o desenvolvimento do raciocínio clínico no curso de medicina da Universidade Federal do Rio Grande do Norte

BACKGROUND: Among the wide range of skills displayed by a medical doctor is undoubtedly the need to use cohesive and well grounded clinical reasoning in order for medical care to be indeed effective. It is in this respect that conceptual maps emerge; these are a methodological innovation that allows a comprehensive, panoramic and associative outlook of theoretical content, making it more practical and applicable to the reality of clinical observation. Promoting learning, learning resources and a feedback system between professor and students, as well as assessing and monitoring the performance of students during their academic training, are the main features of this tool. OBJETIVE: Assess the use of conceptual maps as a teaching-learning tool in the training of undergraduate medical students at Universidade Federal do Rio Grande do Norte (UFRN). METHODOLOGY: Interventional, randomized, cross-sectional study conducted with students from the 3rd and 5th periods of the medical course at UFRN, during the second semester of 2014, totaling 86 participants, divided into two groups: GI (intervention – clinical case resolution with a conceptual map) and GII (control – clinical case resolution without a conceptual map) in each period. RESULTS: The use of conceptual maps to teach liver failure syndrome resulted in a statistically significant cognitive gain for G1 students from the 5th period (GI: 6.8±1.6 and 8.0±1.5, p = 0.024; GII: 7.2±2.1 and 8.0±1.7, p = 0.125, pre and post-intermediate means, respectively), a result not observed in the period 3rd (GI: 7.7±1.3 and 8.0±1.4, p = 0.501; GII: 6.7±1.8 and 7.8±1.8; p=0.068, pre and post-intermediate means, respectively). Students in the 3 rd period gave better responses to the first clinical case, with a larger number of suitable concepts and crosslinks, when they used conceptual maps (GI: 91.3±13.15 and GII: 64.84±22.84, p=0,002). Students in the 5th period exhibited better clinical reasoning and more complete responses using the tool (p=0,01). Most of the students were not aware of the tool (53.8% from the 3rd period and 65.3% from the 5th period). Among those who knew about conceptual maps, most (59.3%) had only used them during high school, 14.8% had never used them and only seven students (25.9%) used them during the medical course. Analysis of open responses, obtained in process assessment showed clear satisfaction and enthusiasm with learning about the new tool, and frequent suggestions to use it at other moments in the course. Assessment of learning profile, using the VARK questionnaire, showed that most students from both periods exhibited a multimodal style. CONCLUSION: Despite their scant knowledge regarding the tool, good acceptability and understanding was observed in the study participants. The conceptual maps allowed cognitive gains, better responses and clinical reasoning in teaching liver failure syndrome to 5th period students.

Comparison of the traditional pharmaceutical validation method versus an assisted pharmaceutical validation in hospitalized patients

Objective: To analyze pharmaceutical interventions that have been carried out with the support of an automated system for validation of treatments vs. the traditional method without computer support. Method: The automated program, ALTOMEDICAMENTOS® version 0, has 925 052 data with information regarding approximately 20 000 medicines, analyzing doses, administration routes, number of days with such a treatment, dosing in renal and liver failure, interactions control, similar drugs, and enteral medicines. During eight days, in four different hospitals (high complexity with over 1 000 beds, 400-bed intermediate, geriatric and monographic), the same patients and treatments were analyzed using both systems. Results: 3,490 patients were analyzed, with 42 155 different treatments. 238 interventions were performed using the traditional system (interventions 0.56% / possible interventions) vs. 580 (1.38%) with the automated one. Very significant pharmaceutical interventions were 0.14% vs. 0.46%; significant was 0.38% vs. 0.90%; non-significant was 0.05% vs. 0.01%, respectively. If both systems are simultaneously used, interventions are performed in 1.85% vs. 0.56% with just the traditional system. Using only the traditional model, 30.5% of the possible interventions are detected, whereas without manual review and only the automated one, 84% of the possible interventions are detected. Conclusions: The automated system increases pharmaceutical interventions between 2.43 to 3.64 times. According to the results of this study the traditional validation system needs to be revised relying on automated systems. The automated program works correctly in different hospitals.

Conhecimento dos estudantes do Curso de Licenciatura em Enfermagem sobre Défice Cognitivo Ligeiro

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de licenciada em Enfermagem

Experiencia y porcentaje de complicaciones de las derivaciones portosistémicas intrahepáticas transyugulares en la Fundación Cardioinfantil

La derivación portosistémica intrahepática transyugular (TIPS) es una técnica importante en el manejo de las complicaciones de la hipertensión portal, en especial en aquellos pacientes candidatos a trasplante hepático. Se trata de un estudio observacional analítico, sin riesgo, en el cual se emplearon técnicas y métodos de investigación documental retrospectivo, y no se realizó ningún tipo de intervención sobre las variables fisiológicas, psicológicas y sociales de la población incluida. Se realizó la descripción demográfica de los pacientes, características clínicas, hallazgos imageneológicos y aspectos técnicos asociados al procedimiento de los pacientes con hipertensión portal que han sido manejados con TIPS en la Fundación CardioInfantil desde Enero 1 de 2007 hasta Junio 30 de 2016. Se incluyeron 54 pacientes de los cuales el 66,7% no presentaron complicaciones inmediatas, tenidas en cuenta desde la terminación del procedimiento y hasta las siguientes 24 horas; sin embargo, 16,9% debutaron con encefalopatía durante este periodo. De las complicaciones tardías, la más frecuente fue la ascitis con un 66,7%, con una mortalidad de 20,4% de los cuales, el 45% de estos fue por shock séptico y falla orgánica secundaria. Aunque el porcentaje de complicaciones asociadas al procedimiento fue alto en nuestros pacientes, se encuentra dentro de los valores reportados en la literatura. Los resultados presentados son un punto de partida para la evaluación del procedimiento en nuestra población y permiten implementar estrategias de mejora que conlleven a incidir de manera positiva en el porcentaje de complicaciones y mortalidad derivadas del procedimiento.

Early renal failure after domino hepatic transplantation using the liver from a compound heterozygous patient with primary hyperoxaluria.

BACKGROUND To cover the shortage of cadaveric organs, new approaches to expand the donor pool are needed. Here we report on a case of domino liver transplantation (DLT) using an organ harvested from a compound heterozygous patient with primary hyperoxaluria (PHO), who underwent combined liver and kidney transplantation. The DLT recipient developed early renal failure with oxaluria. The time to the progression to oxalosis with renal failure in such situations is unknown, but, based on animal data, we hypothesize that calcineurin inhibitors may play a detrimental role. METHODS A cadaveric liver and kidney transplantation was performed in a 52-year-old male with PHO. His liver was used for a 64-year-old patient with a non-resectable, but limited cholangiocarcinoma. RESULTS While the course of the PHO donor was uneventful, in the DLT recipient early post-operative, dialysis-dependent renal failure with hyperoxaluria developed. Histology of a kidney biopsy revealed massive calcium oxalate crystal deposition as the leading aetiological cause. CONCLUSIONS DLT using PHO organs for marginal recipients represents a possible therapeutic approach regarding graft function of the liver. However, it may negatively alter the renal outcome of the recipient in an unpredictable manner, especially with concomitant use of cyclosporin. Therefore, we suggest that, although DLT should be promoted, PHO organs are better excluded from such procedures.

The Queensland liver transplant programme: The first two years

Orthotopic liver transplantation began in Brisbane in January 1985. During the first two years of the programme an assessment committee evaluated 55 patients (38 adults, 17 children). Patients were either accepted for transplantation, rejected as unsuitable or deferred for elective reassessment. All of the 10 adults who were rejected for transplantation because they had 'too advanced' disease died within four months of assessment. Six children who were accepted for transplantation died before a suitable donor liver could be found. In the first two years, 21 orthotopic liver transplantations were performed on 18 patients (adults, 13 patients; children, five patients). Fifteen of 21 grafts were procured from within Queensland. Twelve (67%) patients are alive at three to 23 months and all have been discharged from hospital. Deaths in adults were due to sepsis (three patients), aspiration pneumonitis (one patient), rejection and hepatic artery thrombosis (one patient) and the recurrence of a hepatocellular carcinoma five months after discharge from hospital (one patient). Two patients underwent a second transplantation procedure because of chronic rejection at four months and at 11 months, respectively, after the initial operation. One patient received a second transplant for primary graft failure at four days after the operation. A scoring system which considered the presence of pre-operative patient factors, such as coma, ascites, malnutrition and previous abdominal surgery, partly predicted the operative blood loss and patient survival. In conclusion, orthotopic liver transplantation is being performed in Australia with survival rates that are comparable with those of established overseas units.

Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant

Importance of the field: Tacrolimus is the most commonly used immunosuppressive agent following solid-organ transplantation in children. Its clinical use, however, is complicated by side effects (mainly nephrotoxicity), narrow therapeutic index and pharmacokinetic variability which can result in an increased risk of treatment failure or toxicity. Studies examining inter-individual differences in the expression of the ABCB1 (ATP-binding cassette, subfamily B, member 1) gene (which encodes the drug transporter, P-gp) and its genetic polymorphisms have attempted to elucidate variations in tacrolimus response and disposition in children.