Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl4-treated mice

Chronic liver injury and inflammation lead to hepatic fibrosis, cirrhosis, and liver failure. Embryonic and mesenchymal stem cells have been shown to reduce experimental liver fibrosis but have potential limitations, including the formation of dysplastic precursors, tumors, and profibrogenic cells. Other stem-like cells may reduce hepatic inflammation and fibrosis without tumor and profibrogenic cell formation. To test this hypothesis we transplanted human amnion epithelial cells (hAEC), isolated from term delivered placenta, into immunocompetent C57/BL6 mice at week 2 of a 4-week regimen of carbon tetrachloride (CCl4) exposure to induce liver fibrosis. Two weeks following hAEC infusion, intact cells expressing the human-specific markers inner mitochondrial membrane protein and human leukocyte antigen-G were found in mouse liver without evidence of host rejection of the transplanted cells. Human albumin, known to be produced by hAEC, was detected in sera of hAEC-treated mice. Human DNA was detected in mouse liver and also spleen, lungs, and heart of some animals. Following hAEC transplantation, CCl4-treated animals showed decreased serum ALT levels and reduced hepatocyte apoptosis, compared to controls. hAEC-treated mouse liver had lower TNF-α and IL-6 protein levels and higher IL-10 compared to animals given CCl4 alone. Compared to CCl4 controls, hAEC-treated mice showed fewer activated collagen-producing hepatic stellate cells and less fibrosis area and collagen content. Reduced hepatic TGF-β levels in conjunction with a twofold increase in the active form of the collagen-degrading enzyme matrix metalloproteinase-2 in hAEC-treated mice compared to CCl4 controls may account for the reduction in fibrosis. hAEC transplantation into immunocompetent mice leads to cell engraftment, reduced hepatocyte apoptosis, and decreased hepatic inflammation and fibrosis.

To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt

Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing.

An empirical investigation of health information system failure in regional Sri Lanka

Public health decision making is critically dependant on accurate, timely and reliable information. There is a widespread belief that most of the national and sub-national health information systems fail in providing much needed information support for evidence based health planning and interventions. This situation is more acute in developing nations where resources are either stagnant or decreasing, coupled with the situations of demographic transition and double burden of diseases. Literature abounds with publications, which provide information on misguided health interventions in developing nations, leading to failure and waste of resources. Health information system failure is widely blamed for this situation. Nevertheless, there is a dearth of comprehensive evaluations of existing national or sub-national health information systems, especially in the region of South-East Asia. This study makes an attempt to bridge this knowledge gap by evaluating a regional health information system in Sri Lanka. It explores the strengths and weaknesses of the current health information system and related causative factors in a decentralised health system and then proposes strategic recommendations for reform measures. A mix methodological and phased approach was adopted to reach the objectives. An initial self administered questionnaire survey was conducted among health managers to study their perceptions in relation to the regional health information system and its management support. The survey findings were used to establish the presence of health information system failure in the region and also as a precursor to the more in-depth case study which was followed. The sources of data for the case study were literature review, document analysis and key stake holder interviews. Health information system resources, health indicators, data sources, data management, data quality, and information dissemination were the six major components investigated. The study findings reveal that accurate, timely and reliable health information is unavailable and therefore evidence based health planning is lacking in the studied health region. Strengths and weaknesses of the current health information system were identified and strategic recommendations were formulated accordingly. It is anticipated that this research will make a significant and multi-fold contribution for health information management in developing countries. First, it will attempt to bridge an existing knowledge gap by presenting the findings of a comprehensive case study to reveal the strengths and weaknesses of a decentralised health information system in a developing country. Second, it will enrich the literature by providing an assessment tool and a research method for the evaluation of regional health information systems. Third, it will make a rewarding practical contribution by presenting valuable guidelines for improving health information systems in regional Sri Lanka.

Dying in hospital: medical failure or natural outcomes?

The purpose of this study was to describe patterns of medical and nursing practice in the care of patients dying of oncological and hematological malignancies in the acute care setting in Australia. A tool validated in a similar American study was used to study the medical records of 100 consecutive patients who died of oncological or hematological malignancies before August 1999 at The Canberra Hospital in the Australian Capital Territory. The three major indicators of patterns of end-of-life care were documentation of Do Not Resuscitate (DNR) orders, evidence that the patient was considered dying, and the presence of a palliative care intention. Findings were that 88 patients were documented DNR, 63 patients' records suggested that the patient was dying, and 74 patients had evidence of a palliative care plan. Forty-six patients were documented DNR 2 days or less prior to death and, of these, 12 were documented the day of death. Similar patterns emerged for days between considered dying and death, and between palliative care goals and death. Sixty patients had active treatment in progress at the time of death. The late implementation of end-of-life management plans and the lack of consistency within these plans suggested that patients were subjected to medical interventions and investigations up to the time of death. Implications for palliative care teams include the need to educate health care staff and to plan and implement policy regarding the management of dying patients in the acute care setting. Although the health care system in Australia has cultural differences when compared to the American context, this research suggests that the treatment imperative to prolong life is similar to that found in American-based studies.

Metabolite profiling and pathway analysis of acute hepatitis rats by UPLC-ESI MS combined with pattern recognition methods

BACKGROUND & AIMS Metabolomics is comprehensive analysis of low-molecular-weight endogenous metabolites in a biological sample. It could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity to develop predictive biomarkers that could provide valuable insights into the mechanisms of diseases. The aim of this study was to elucidate the changes in endogenous metabolites and to phenotype the metabolic profiling of d-galactosamine (GalN)-inducing acute hepatitis in rats by UPLC-ESI MS. METHODS The systemic biochemical actions of GalN administration (ip, 400 mg/kg) have been investigated in male wistar rats using conventional clinical chemistry, liver histopathology and metabolomic analysis of UPLC- ESI MS of urine. The urine was collected predose (-24 to 0 h) and 0-24, 24-48, 48-72, 72-96 h post-dose. Mass spectrometry of the urine was analysed visually and via conjunction with multivariate data analysis. RESULTS Results demonstrated that there was a time-dependent biochemical effect of GalN dosed on the levels of a range of low-molecular-weight metabolites in urine, which was correlated with developing phase of the GalN-inducing acute hepatitis. Urinary excretion of beta-hydroxybutanoic acid and citric acid was decreased following GalN dosing, whereas that of glycocholic acid, indole-3-acetic acid, sphinganine, n-acetyl-l-phenylalanine, cholic acid and creatinine excretion was increased, which suggests that several key metabolic pathways such as energy metabolism, lipid metabolism and amino acid metabolism were perturbed by GalN. CONCLUSION This metabolomic investigation demonstrates that this robust non-invasive tool offers insight into the metabolic states of diseases.

A randomized controlled trial of self-management programme improves health-related outcomes of older people with heart failure

Aims This paper is a report on the effectiveness of a self-management programme based on the self-efficacy construct, in older people with heart failure. Background Heart failure is a major health problem worldwide, with high mortality and morbidity, making it a leading cause of hospitalization. Heart failure is associated with a complex set of symptoms that arise from problems in fluid and sodium retention. Hence, managing salt and fluid intake is important and can be enhanced by improving patients' self-efficacy in changing their behaviour. Design Randomized controlled trial. Methods Heart failure patients attending cardiac clinics in northern Taiwan from October 2006–May 2007 were randomly assigned to two groups: control (n = 46) and intervention (n = 47). The intervention group received a 12-week self-management programme that emphasized self-monitoring of salt/fluid intake and heart failure-related symptoms. Data were collected at baseline as well as 4 and 12 weeks later. Data analysis to test the hypotheses used repeated-measures anova models. Results Participants who received the intervention programme had significantly better self-efficacy for salt and fluid control, self-management behaviour and their heart failure-related symptoms were significantly lower than participants in the control group. However, the two groups did not differ significantly in health service use. Conclusion The self-management programme improved self-efficacy for salt and fluid control, self-management behaviours, and decreased heart failure-related symptoms in older Taiwanese outpatients with heart failure. Nursing interventions to improve health-related outcomes for patients with heart failure should emphasize self-efficacy in the self-management of their disease.

Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.

Meeting the nutrition challenge of stage 3 renal failure : considerations for nursing practice

Self-care management is needed for effective management of chronic kidney disease. The main aim for treatment or management of chronic kidney disease is to delay the worsening of kidney function, and to prevent or to manage the co-morbidities. Selfcare management is not easy, and patients will face many challenges, especially when they cannot get use to the new treatment plan. One of the challenges they face is dietary restriction, which is a very important aspect in any self-care management programme. Chronic kidney disease patients require a low-protein, low-sodium, low-potassium, and low-phosphorus diet. There are several strategies patients can undertake to ensure adherence, such as self-monitoring their dietary habits and type of food consumed using a food diary; involving social support, such as family members and spouse to help them to adhere to their diet restrictions; setting goals and providing positive reinforcement when they achieved the targeted goals; joining self-management programmes to equip themselves with the necessary skills so that they can better adhere to the treatment regimes, including diet restriction; and lastly, having the knowledge about their regime, and using this knowledge to help them understand and improve their adherence.

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.