Glutathione transferase isozyme genotypes in patients with prostate and bladder carcinoma

Genotype distributions for GSTP1, GSTM1, and GSTT1 were determined in 91 patients with prostatic carcinoma and 135 patients with bladder carcinoma and compared with those in 127 abdominal surgery patients without malignancies. None of the genotypes differed significantly with respect to age or sex among controls or cancer patients. In the group of prostatic carcinoma patients, GSTT1 null allele homozygotes were more prevalent (25% in carcinoma patients vs 13% in controls, Fisher P=0.02, χ2 P = 0.02, OR = 2.31, CI = 1.17-4.59) and the combined M1-/T1-null genotype was also more frequent (9% vs 3%, χ2 P= 0.02, Fisher P = 0.03). Homozygosity for the GSTM1 null allele was more frequent among bladder carcinoma patients (59% in bladder carcinoma patients vs 45% in controls, Fisher P = 0.03, χ2 P = 0.02, OR = 1.76, CI = 1.08-2.88). In contrast to a previous report, no significant increase in the frequency of the GSTP1b allele was found in the tumor patients. Except for the combined GSTM1-/T1-null genotype in prostatic carcinoma, none of the combined genotypes showed a significant association with either of the cancers. These findings suggest that specific single polymorphic GST genes, that is GSTM1 in the case of bladder cancer and GSTT1 in the case of prostatic carcinoma, are most relevant for the development of these urological malignancies among the general population in Central Europe.

Fine-needle aspiration cytology of Merkel cell carcinoma-A review of 69 cases

Background This study reviewed the clinical presentation, cytologic findings and the immunophenotype of 69 Merkel Cell Carcinoma (MCC) cases sampled by FNA. Methods Demographic and clinical data, the cytology findings and results of ancillary testing were reviewed. Results Median patient age was 78 years (37 – 104) with a 1:1.8 female to male ratio. The most common FNA sites sampled included lymph nodes in the neck, the axillary region, the inguinal region and the parotid gland. Most patients had a history of MCC (68%) &/or non-MCC malignancy (70%). The common cytologic pattern was a cellular smear with malignant cells arranged in a dispersed pattern with variable numbers of disorganised groups of cells. Cytoplasm was scant or absent and nuclei showed mild to moderate anisokaryosis, stippled chromatin, inconspicuous nucleoli and nuclear molding. Numerous apoptotic bodies were often present. Cell block samples (28 cases) were usually positive for cytokeratins in a perinuclear dot pattern, including 88% of cases with CK20 positivity. CD56 was the most sensitive (95%) neuroendocrine marker on cell blocks and was also positive with flow cytometry in 9 cases tested. Conclusions MCC is most commonly seen in FNA specimens from the head and neck of elderly patients, often with a history of previous skin lesions. Occasional cases present in younger patients and some may be mistaken for other round blue cell tumors, such as lymphoma. CD 56 may be a useful marker in cell block preparations and in flow cytometric analysis of MCC.

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.

Emotional effort and perceived support in renal nursing: A comparative interview study

Background: Social support is an important moderator of poor well-being outcomes for nurses engaged in emotional labour with patients; however, the most effective support for renal nurses is not well understood compared with other specialties. Objectives: To identify patterns and themes in how renal nurses and two other specialties engage with patients’ emotional expressions, express their own emotion and access and provide support for emotional expenditure. Method: Renal, emergency and palliative care nurses from Perth, Western Australia, were interviewed. Results: Renal nurses engage in significant amounts of emotional labour with patients, and identify co-workers as the most important source of support due to their availability and a sense of shared experience. However, comparative analysis showed that renal nurses do not recognise their emotional expenditure as readily and have less certainty of co-worker support. Conclusions: Because their high levels of emotional engagement with patients are mostly positive, renal nurses are less prepared than other nurses to manage difficult emotional situations. As co-worker support is highly valued, organisations should train renal nurses specifically to support one another.

Defining a 3-dimensional (3D) in vitro model to study immune cell and renal cell interactions

This study aimed to develop a 3-Dimensional (D) hydrogel system for the co-culture of autologous human renal and immune cells. Previous studies have shown that human renal epithelial cells are able to modulate autologous immune cell responses. However, these studies were undertaken in a standard 2D culture system. The 3D model was developed to re-capitulate these observations within a more physiological relevant in vivo like environment.

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.

The effectiveness of interventions which promote self-management for people with End Stage Renal Disease undergoing haemodialysis

Review Objectives: This systematic review seeks to establish what best practice is for: Interventions which promote self-management for patients with End Stage Renal Disease (ERSD) undergoing Haemodialysis. Review questions: 1) Do education interventions improve self-management for patients with end stage renal disease? 2) Do psychosocial interventions such as Cognitive Behavioural Therapy, behavioural therapy or other counselling therapies and social support, improve self-management for patients with end stage renal disease? Criteria for considering studies for this review: Types of participants: This component of the review will consider studies with: • All adults over the age of 18 years • Patients with end stage renal disease • Undergoing haemodialysis Types of interventions/Phenomena of Interest: All studies evaluating the following interventions will be considered for inclusion in the review such as: Interventions which promote self management including: • Education interventions. • Psychosocial interventions such as cognitive behavioural therapy and other behavioural therapies, counselling and social support. Types of outcome measures/anticipated outcomes: This component of the review will consider studies that include the following outcomes: • Adherence with haemodialysis treatment, • Depression and/or anxiety, • Quality of life, • Carer burnout, • Social support • Patient satisfaction • Adverse events potentially attributable to the intervention or control treatment • Cost effectiveness of home haemodialysis Keywords chronic kidney failure; renal failure; end stage renal disease; chronic kidney disease

A Mouse Model of Early-Onset Renal Failure Due to a Xanthine Dehydrogenase Nonsense Mutation

Chronic kidney disease (CKD) is characterized by renal fibrosis that can lead to end-stage renal failure, and studies have supported a strong genetic influence on the risk of developing CKD. However, investigations of the underlying molecular mechanisms are hampered by the lack of suitable hereditary models in animals. We therefore sought to establish hereditary mouse models for CKD and renal fibrosis by investigating mice treated with the chemical mutagen N-ethyl-N-nitrosourea, and identified a mouse with autosomal recessive renal failure, designated RENF. Three-week old RENF mice were smaller than their littermates, whereas at birth they had been of similar size. RENF mice, at 4-weeks of age, had elevated concentrations of plasma urea and creatinine, indicating renal failure, which was associated with small and irregularly shaped kidneys. Genetic studies using DNA from 10 affected mice and 91 single nucleotide polymorphisms mapped the Renf locus to a 5.8Mbp region on chromosome 17E1.3. DNA sequencing of the xanthine dehydrogenase (Xdh) gene revealed a nonsense mutation at codon 26 that co-segregated with affected RENF mice. The Xdh mutation resulted in loss of hepatic XDH and renal Cyclooxygenase-2 (COX-2) expression. XDH mutations in man cause xanthinuria with undetectable plasma uric acid levels and three RENF mice had plasma uric acid levels below the limit of detection. Histological analysis of RENF kidney sections revealed abnormal arrangement of glomeruli, intratubular casts, cellular infiltration in the interstitial space, and interstitial fibrosis. TUNEL analysis of RENF kidney sections showed extensive apoptosis predominantly affecting the tubules. Thus, we have established a mouse model for autosomal recessive early-onset renal failure due to a nonsense mutation in Xdh that is a model for xanthinuria in man. This mouse model could help to increase our understanding of the molecular mechanisms associated with renal fibrosis and the specific roles of XDH and uric acid. © 2012 Piret et al.

Spatiotemporal transmission dynamics of hemorrhagic fever with renal syndrome in China, 2005-2012

Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures. Methods Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences. Results A total of 100,868 cases were reported during 2005–2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05). Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties. Conclusions This study identified significant space-time clusters of HFRS in China during 2005–2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.

Multiple primary cancers associated with Merkel cell carcinoma in Queensland, Australia, 1982-2011

The relatively high incidence of Merkel cell carcinoma (MCC) in Queensland provides a valuable opportunity to examine links with other cancers. A retrospective cohort study was performed using data from the Queensland Cancer Registry. Standardized incidence ratios (SIRs) were used to approximate the relative risk of being diagnosed with another primary cancer either following or prior to MCC. Patients with an eligible first primary MCC (n=787) had more than double the expected number of subsequent primary cancers (SIR=2.19, 95% confidence interval (CI)=1.84–2.60; P<0.001). Conversely, people who were initially diagnosed with cancers other than MCC were about two and a half times more likely to have a subsequent primary MCC (n=244) compared with the general population (SIR=2.69, 95% CI=2.36–3.05; P<0.001). Significantly increased bi-directional relative risks were found for melanoma, lip cancer, head and neck cancer, lung cancer, myelodysplastic diseases, and cancer with unknown primary site. In addition, risks were elevated for female breast cancer and kidney cancer following a first primary MCC, and for subsequent MCCs following first primary colorectal cancer, prostate cancer, non-Hodgkin lymphoma, or lymphoid leukemia. These results suggest that several shared pathways are likely for MCC and other cancers, including immunosuppression, UV radiation, and genetics.

Increased risk of emergency hospital admissions for children with renal diseases during heatwaves in Brisbane, Australia

Background Heatwaves have a significant impact on population health including both morbidity and mortality. In this study we examined the association between heatwaves and emergency hospital admissions (EHAs) for renal diseases in children (aged 0–14 years) in Brisbane, Australia. Methods Daily data on EHAs for renal diseases in children and exposure to temperature and air pollution were obtained for Brisbane city from January 1, 1996 to December 31, 2005. A time-stratified case-crossover design was used to compare the risks for renal diseases between heatwave and non-heatwave periods. Results There were 1565 EHAs for renal diseases in children during the study period. Heatwaves exhibited a significant impact on EHAs for renal diseases in children after adjusting for confounding factors (odds ratio: 3.6; 95% confidence interval: 1.4–9.5). The risk estimates differed with lags and the use of different heatwave definitions. Conclusions There was a significant increase in EHAs for renal diseases in children during heatwaves in Brisbane, a subtropical city where people are well accustomed to warm weather. This finding may have significant implications for pediatric renal care, particularly in subtropical and tropical regions.