Clinical outcomes of vitamin D deficiency and supplementation in cancer patients

Results of recent studies suggest that circulating levels of vitamin D may play an important role in cancer-specific outcomes. The present systematic review was undertaken to determine the prevalence of vitamin D deficiency (<25 nmol/L) and insufficiency (25-50 nmol/L) in cancer patients and to evaluate the association between circulating calcidiol (the indicator of vitamin D status) and clinical outcomes. A systematic search of original, peer-reviewed studies on calcidiol at cancer diagnosis, and throughout treatment and survival, was conducted yielding 4,706 studies. A total of 37 studies met the inclusion criteria for this review. Reported mean blood calcidiol levels ranged from 24.7 to 87.4 nmol/L, with up to 31% of patients identified as deficient and 67% as insufficient. The efficacy of cholecalciferol supplementation for raising the concentration of circulating calcidiol is unclear; standard supplement regimens of <1,000 IU D3 /day may not be sufficient to maintain adequate concentrations or prevent decreasing calcidiol. Dose-response studies linking vitamin D status to musculoskeletal and survival outcomes in cancer patients are lacking.

Radiolabelled somatostatin analogue scintigraphy in oncology

Somatostatin analogue scintigraphy represents a new technique employing radiolabelled peptides to detect specific receptor-bearing lesions. 111Indium diethylenetriaminopentaacetic acid-linked octreotide (111In-DTPA-D-Phe1 octreotide), also known as [111In]pentetreotide or OctreoScan, is now established in the management of patients with neuroendocrine gastrointestinal tract and pancreatic tumours, and has proved effective in localizing disease sites in lung, breast and medullary thyroid carcinomas, lymphomas, meningiomas and others. In these conditions (a) the imaging of all disease sites at a single sitting (in a proportion of patients) thereby making further investigations unnecessary, (b) the localization of otherwise unexpected metastatic deposits and (c) the detection of residual disease not found by other means suggest that [111In]pentetreotide may be a useful adjunct in the diagnostic evaluation of patients with somatostatin receptor-bearing tumours.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Chemotherapy for upper gastrointestinal tumours

The aim of this review is to identify current chemotherapy treatment for tumours of the oesophagus, stomach, pancreas, and liver. The role of both neoadjuvant, adjuvant, and palliative chemotherapy regimens will be discussed. This review will be of interest to oncologists in clarifying current issues regarding chemotherapy, and to physicians in other medical specialties, to increase their general understanding of benefits and drawbacks of chemotherapy in this patient group.

CPD : Using evidence based clinical practice guidelines in the management of anaemia in patients with chronic renal failure

Anaemia is a chronic problem in patients with renal insufficiency, especially chronic renal failure (CRF). In patients with CRF, anaemia is primarily due to a deficiency in erythropoietin (EPO), a glycoprotein growth factor that stimulates RBC production. The long-term effects and burden of anaemia for patients with CRF can be physical, emotional and financial. With efficient, systematic management of anaemia, clinicians have the potential to realise not only better clinical outcomes for CRF patients but also significant cost savings for them and the health system. During the last decade, significant advances have been made in clinicians’ understanding of how best to manage anaemia in this vulnerable population. One of the most important efforts to improve clinical practice has been the development of best practice guidelines.

A visual profile of Queensland indigenous and non-indigenous school children, and the association between vision and reading

This research investigated the prevalence of vision disorders in Queensland Indigenous primary school children, creating the first comprehensive visual profile of Indigenous children. Findings showed reduced convergence ability and reduced visual information processing skills were more common in Indigenous compared to non-Indigenous children. Reduced visual information processing skills were also associated with reduced reading outcomes in both groups of children. As early detection of visual disorders is important, the research also reviewed the delivery of screening programs across Queensland and proposed a model for improved coordination and service delivery of vision screening to Queensland school children.

Serum 25-hydroxy vitamin D concentrations are more deficient/insufficient in peritoneal dialysis than haemodialysis patients in a sunny climate

Background Research has identified associations between serum 25(OH)D and a range of clinical outcomes in chronic kidney disease and wider populations. The present study aimed to investigate vitamin D deficiency/insufficiency in dialysis patients and the relationship with vitamin D intake and sun exposure. Methods A cross-sectional study was used. Participants included 30 peritoneal dialysis (PD) (43.3% male; 56.87 ± 16.16 years) and 26 haemodialysis (HD) (80.8% male; 63.58 ± 15.09 years) patients attending a department of renal medicine. Explanatory variables were usual vitamin D intake from diet/supplements (IU day−1) and sun exposure (min day−1). Vitamin D intake, sun exposure and ethnic background were assessed by questionnaire. Weight, malnutrition status and routine biochemistry were also assessed. Data were collected during usual department visits. The main outcome measure was serum 25(OH)D (nm). Results Prevalence of inadequate/insufficient vitamin D intake differed between dialysis modality, with 31% and 43% found to be insufficient (<50 nm) and 4% and 33% found to be deficient (<25 nm) in HD and PD patients, respectively (P < 0.001). In HD patients, there was a correlation between diet and supplemental vitamin D intake and 25(OH)D (ρ = 0.84, P < 0.001) and average sun exposure and 25(OH)D (ρ = 0.50, P < 0.02). There were no associations in PD patients. The results remained significant for vitamin D intake after multiple regression, adjusting for age, gender and sun exposure. Conclusions The results highlight a strong association between vitamin D intake and 25(OH)D in HD but not PD patients, with implications for replacement recommendations. The findings indicate that, even in a sunny climate, many dialysis patients are vitamin D deficient, highlighting the need for exploration of determinants and consequences.

Perspectives about exercise from adults with venous leg ulcers : an exploratory study

Objective Exercise has the potential to offer a range of health benefits in addition to improving healing outcomes for people with venous leg ulcers. However despite evidence based recommendations, most of these individuals do not engage in regular exercise. The aim of this study was to gain an understanding of the perspectives of adults with venous leg ulcers, in relation to exercise. Method This was a qualitative design using semi-structured interviews and discussions. Ten participants with venous leg ulceration volunteered to participate. Recruitment was through a specialist wound clinic. Verbatim data were collected by an experienced moderator using a semi-structured guide. Data saturation was reached after three group discussions and two interviews. A random selection of transcripts was sent back to the participants for verification. Thematic content analysis was used to determine major themes and categories. Two transcripts were independently analysed, categories and themes independently developed, cross checked and found comparable. Remaining transcripts were analysed using developed categories and codes. Results Regardless of their current exercise routine, participants reported exercising prior to venous leg ulceration and expressed an interest in either becoming active or maintaining an active lifestyle. Overall four themes emerged from the findings: i) participant understanding of the relationship between chronic venous insufficiency and exercise patterns, ii) fear of harm impacts upon positive beliefs and attitudes to exercise, iii) perceived factors limit exercise and iv) structured management facilitates exercise. Conclusion The value of exercise in improving outcomes in venous leg ulcers lies in its capacity to promote venous return and reduce the risk of secondary conditions in this population. Despite motivation and interest in being exercise active, people with venous leg ulcers report many obstacles. Further exploration of mechanisms that assist this patient population and promote understanding about management of barriers, coupled with promotion of enabling factors is vital for improving their exercise participation.

Generation and assessment of accuracy of Digital Elevation Model by using Pcigeomatica (10.3)

This study aims to assess the accuracy of Digital Elevation Model (DEM) which is generated by using Toutin’s model. Thus, Toutin’s model was run by using OrthoEngineSE of PCI Geomatics 10.3.Thealong-track stereoimages of Advanced Spaceborne Thermal Emission and Reflection radiometer (ASTER) sensor with 15 m resolution were used to produce DEM on an area with low and near Mean Sea Level (MSL) elevation in Johor Malaysia. Despite the satisfactory pre-processing results the visual assessment of the DEM generated from Toutin’s model showed that the DEM contained many outliers and incorrect values. The failure of Toutin’s model may mostly be due to the inaccuracy and insufficiency of ASTER ephemeris data for low terrains as well as huge water body in the stereo images.

Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

Affinity purification of plasmid DNA directly from crude bacterial cell lysates

We have shown previously that a sequence-specific DNA-binding protein based on the Lac repressor protein can isolate pre-purified DNA efficiently from simple buffer solution but our attempts to purify plasmids directly from crude starting materials were disappointing with unpractically low DNA yields. We have optimized tbe procedure and present a simple affinity methodology whereby plasmid DNA is purified directly by mixing two crude cell lysates, one cell lysate containing the plasmid and the other the protein affinity ligand, without the need for treatment by RNaseA. After IMAC chromatography, high purity supercoiled DNA is recovered in good yields of 100-150 μg plasmid per 200 mL shake flask culture. Moreover, the resulting DNA is free from linear or open-circular plasmid DNA, genomic DNA, RNA, and protein, to the limits of our detection. Furthermore, we show that lyophilized affinity ligand can be stored at room temperature and re-hydrated for use when required.

Frequency of convergence and accommodative disorders in a clinical population of Mashhad, Iran

Purpose To investigate the frequency of convergence and accommodation anomalies in an optometric clinical setting in Mashhad, Iran, and to determine tests with highest accuracy in diagnosing these anomalies. Methods From 261 patients who came to the optometric clinics of Mashhad University of Medical Sciences during a month, 83 of them were included in the study based on the inclusion criteria. Near point of convergence (NPC), near and distance heterophoria, monocular and binocular accommodative facility (MAF and BAF, respectively), lag of accommodation, positive and negative fusional vergences (PFV and NFV, respectively), AC/A ratio, relative accommodation, and amplitude of accommodation (AA) were measured to diagnose the convergence and accommodation anomalies. The results were also compared between symptomatic and asymptomatic patients. The accuracy of these tests was explored using sensitivity (S), specificity (Sp), and positive and negative likelihood ratios (LR+, LR−). Results Mean age of the patients was 21.3 ± 3.5 years and 14.5% of them had specific binocular and accommodative symptoms. Convergence and accommodative anomalies were found in 19.3% of the patients; accommodative excess (4.8%) and convergence insufficiency (3.6%) were the most common accommodative and convergence disorders, respectively. Symptomatic patients showed lower values for BAF (p = .003), MAF (p = .001), as well as AA (p = .001) compared with asymptomatic patients. Moreover, BAF (S = 75%, Sp = 62%) and MAF (S = 62%, Sp = 89%) were the most accurate tests for detecting accommodative and convergence disorders in terms of both sensitivity and specificity. Conclusions Convergence and accommodative anomalies are the most common binocular disorders in optometric patients. Including tests of monocular and binocular accommodative facility in routine eye examinations as accurate tests to diagnose these anomalies requires further investigation.

The lipophilic opioids: Fentanyl, alfentanil, sufentanil and remifentanil

discusses fentanyl, alfentanil, sufentanil, and remifentanil which are synthetic opioid analgesics with high affinity for the mu opioid receptor. They have been widely adopted in anaesthetic practice for various surgical procedures (e.g. in cardiac surgery) and for long-term analgesia and sedation. Important pharmacokinetic differences between these analgesics have been described, and this chapter addresses how the pharmacokinetic profile of each analgesic is affected by many factors, including patient age, plasma protein content, acid–base balance status, cardiopulmonary bypass, changes in hepatic blood flow, and the co-administration of other drugs which compete for plasma protein carriers and metabolic pathways, although their profile is not significantly affected by renal insufficiency or compensated hepatic dysfunction, which has major clinical implications.

AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle

Equine metabolic syndrome is characterized by obesity and insulin resistance (IR). Currently, there is no effective pharmacological treatment for this insidious disease. Glucose uptake is mediated by a family of glucose transporters (GLUT), and is regulated by insulin-dependent and -independent pathways, including 5-AMP-activated protein kinase (AMPK). Importantly, the activation of AMPK, by 5-aminoimidazole- 4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in both healthy and diabetic humans. However, whether AICAR promotes glucose uptake in horses has not been established. It is hypothesized that AICAR administration would enhance glucose transport in equine skeletal muscle through AMPK activation. In this study, the effect of an intravenous AICAR infusion on blood glucose and insulin concentrations, as well as on GLUT expression and AMPK activation in equine skeletal muscle (quantified by Western blotting) was examined. Upon administration, plasma AICAR rapidly reached peak concentration. Treatment with AICAR resulted in a decrease (P < 0.05) in blood glucose and an increase (P < 0.05) in insulin concentration without a change in lactate concentration. The ratio of phosphorylated to total AMPK was increased (P < 0.05) in skeletal muscle. While GLUT4 and GLUT1 protein expression remained unchanged, GLUT8 was increased (P < 0.05) following AICAR treatment. Up-regulation of GLUT8 protein expression by AICAR suggests that this novel GLUT isoform plays an important role in equine muscle glucose transport. In addition, the data suggest that AMPK activation enhances pancreatic insulin secretion. Collectively, the findings suggest that AICAR acutely promotes muscle glucose uptake in healthy horses and thus its therapeutic potential for managing IR requires investigation.

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.