Demonstration That Circulating 1α,25-Dihydroxyvitamin D is Loosely Regulated in Normal Children

The effects of vitamin D, 2.5 mg (100,000 U)/d for 4 d, on serum calcium, serum 25-hydroxyvitamin D (25-OHD) and serum 1a,25-dihydroxyvitamin D (1a,25(OH)2D) were compared in 24 normal adults and 12 normal children. The daily dose of vitamin D was 1,500 U/kg body wt in children weighing \u3c45 kg. Vitamin D increased mean serum calcium from 9.5±0.1 to 9.8±0.1 mg/dl (P \u3c 0.05), increased mean serum phosphorus from 4.6±0.1 to 5.0±0.1 mg/dl (P \u3c 0.01), increased mean serum 25-OHD from 25±3 to 34±4 ng/ml (P \u3c 0.001), and increased mean serum 1a,25(OH)2D from 34±3 to 42±4 pg/ml (P \u3c 0.02) in children. In contrast, vitamin D increased mean serum 25-OHD from 18±2 to 39±6 ng/ml (P \u3c 0.001) and did not change mean serum calcium (9.4±0.1 vs. 9.5±0.1 mg/dl), mean serum phosphorus (4.0±0.1 vs. 4.1±0.1 mg/dl), or mean serum 1a,25(OH)2D (31±2 vs. 29±3 pg/ml) in adults. Mean serum 1a,25(OH)2D was significantly higher after vitamin D in children than in adults (P \u3c 0.02). These results provide evidence that circulating 1a,25(OH)2D is not as tightly regulated in children as it is in adults. This difference in regulation could account in part for the higher values for serum 1a,25(OH)2D observed in children

An analysis of the role of serum in parathyroid hormone-induced bone resorption in tissue culture

1. 1. Several chemically-defined media were tested for their capacity to support parathyroid hormone-induced 45Ca release from embryonic bone. None was completely satisfactory.2. 2. A medium consisting of 2 per cent serum in CMRL 1066 would support the parathyroid hormone effect as well as did media containing 50 per cent serum plus 50 per cent CMRL 1066 or 50 per cent Eagle Basal Medium.3. 3. The albumin content of rat serum could be substituted for the whole serum without loss of the observed parathyroid hormone effect. Different albumin preparations varied in their capacity to support the response. Serum globulins, gelatin, histone, heparin or insulin could not replace serum.4. 4. A number of substances enhanced 45Ca release in the absence of parathyroid hormone. Bovine albumin (fraction V) was the most effective preparation tested.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33342/1/0000739.pd

Evidence for Extrarenal Production of 1a,25-Dihydroxyvitamin D in Man

Recent studies provide evidence for extrarenal production of 1a,25-dihydroxyvitamin D [1a,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1a,25(OH)2D were measured in eight adult anephric subjects. All were undergoing hemodialysis and three of them were receiving vitamin D, 50,000 or 100,000 U/d. Serum vitamin D was elevated in two of the patients given vitamin D and was abnormally low in the others. Mean serum 25-OHD was increased in patients given vitamin D (94.0±7.6 ng/ml) and was normal in the others (16.4±0.9 ng/ml, P \u3c 0.001). Mean serum 24,25(OH)2D was normal in patients given vitamin D (1.38±0.27 ng/ml) and was low in the others (0.25±0.08 ng/ml, P \u3c 0.001). Serum 24,25(OH)2D correlated significantly with serum 25-OHD (r = 0.848, P \u3c 0.01). Mean serum 1a,25(OH)2D determined by receptor assay was 5.8±1.9 pg/ml in patients who were not given vitamin D and was 14.1±0.6 in those who were given vitamin D (P \u3c 0.001). Serum 1a,25(OH)2D correlated significantly with serum 25-OHD (r = 0.911, P \u3c 0.01). Mean serum 1a,25(OH)2D, measured by bioassay, was 8.3±1.9 pg/ml in patients who were not given vitamin D and was 15.9±2.4 pg/ml in those who were given vitamin D (P \u3c 0.05). There was a significant correlation between the values for serum 1a,25(OH)2D obtained with the two methods (r = 0.728, P \u3c 0.01). The results (a) provide evidence in man for extrarenal production of both 24,25(OH)2D and, by two independent assays, of 1a,25(OH)2D, and (b) indicate that serum values of the two dihydroxy metabolites of vitamin D in anephric subjects vary with the serum concentration of the precursor 25-OHD

Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

Abstract We have examined whether Ad.sT?RFc and TAd.sT?RFc, two oncolytic viruses expressing soluble transforming growth factor-? receptor II fused with human Fc (sTGF?RIIFc), can be developed to treat bone metastasis of prostate cancer. Incubation of PC-3 and DU-145 prostate tumor cells with Ad.sT?RFc and TAd.sT?RFc produced sTGF?RIIFc and viral replication; sTGF?RIIFc caused inhibition of TGF-?-mediated SMAD2 and SMAD3 phosphorylation. Ad(E1-).sT?RFc, an E1? adenovirus, produced sTGF?RIIFc but failed to replicate in tumor cells. To examine the antitumor response of adenoviral vectors, PC-3-luc cells were injected into the left heart ventricle of nude mice. On day 9, mice were subjected to whole-body bioluminescence imaging (BLI). Mice bearing hind-limb tumors were administered viral vectors via the tail vein on days 10, 13, and 17 (2.5?1010 viral particles per injection per mouse, each injection in a 0.1-ml volume), and subjected to BLI and X-ray radiography weekly until day 53. Ad.sT?RFc, TAd.sT?RFc, and Ad(E1-).sT?RFc caused significant inhibition of tumor growth; however, Ad.sT?RFc was the most effective among all the vectors. Only Ad.sT?RFc and TAd.sT?RFc inhibited tumor-induced hypercalcemia. Histomorphometric and synchrotron micro-computed tomographic analysis of isolated bones indicated that Ad.sT?RFc induced significant reduction in tumor burden, osteoclast number, and trabecular and cortical bone destruction. These studies suggest that Ad.sT?RFc and TAd.sT?RFc can be developed as potential new therapies for prostate cancer bone metastasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98454/1/hum%2E2012%2E040.pd

A case report of bilateral synovial chondromatosis of the ankle

<p>Abstract</p> <p>Background</p> <p>Synovial chondromatosis is a rare, generally benign condition which affects synovial membranes. It most commonly involves large joints such as the knee, hip, and elbow, but its presence in smaller joints has also been reported. The diagnosis of synovial chondromatosis is commonly made following a thorough history, physical examination, and radiographic examination. Patients may report pain and swelling within a joint which is often aggravated with physical activity.</p> <p>Case presentation</p> <p>A rare case of bilateral synovial chondromatosis of the ankle is reviewed. A 26 year-old male presented with chronic bilateral ankle pain. Physical examination suggested and imaging confirmed multiple synovial chondromatoses bilaterally, likely secondary to previous trauma.</p> <p>Conclusion</p> <p>The clinical and imaging findings, along with potential differential diagnoses, are described. Since this condition tends to be progressive but self-limiting, indications for surgery depend on the level of symptomatic presentation in addition to the functional demands of the patient. Following a surgical consultation, it was decided that it was not appropriate to pursue surgery at the present time.</p

Watchfully checking rapport with the Primary Child Health Care nurses - a theoretical model from the perspective of parents of foreign origin

<p>Abstract</p> <p>Background</p> <p>Worldwide, multicultural interaction within health care seems to be challenging and problematic. This is also true among Primary Child Health Care nurses (PCHC nurses) in the Swedish Primary Child Health Care services (PCHC services). Therefore, there was a need to investigate the parents' perspective in-depth.</p> <p>Aim</p> <p>The aim of the study was to construct a theoretical model that could promote further understanding of the variety of experiences of parents of foreign origin regarding their interaction with the PCHC nurses at PCHC services.</p> <p>Method</p> <p>The study used Grounded Theory Methodology. Twenty-one parents of foreign origin in contact with PCHC servicies were interviewed.</p> <p>Results</p> <p>In our study parents were watchfully checking rapport, i.e. if they could perceive sympathy and understanding from the PCHC nurses. This was done by checking the nurse's demeanour and signs of judgement. From these interviews we created a theoretical model illustrating the interactive process between parents and PCHC nurses.</p> <p>Conclusion</p> <p>We found it to be of utmost importance for parents to be certain that it was possible to establish rapport with the PCHC nurse. If not, disruptions in the child's attendance at PCHC services could result. PCHC nurses can use the theoretical model resulting from this study as a basis for understanding parents, avoiding a demeanour and judgements that may cause misunderstandings thus promoting high-quality interaction in PCHC services.</p

Reporting of clinical trials: a review of research funders' guidelines

BACKGROUND: Randomised controlled trials (RCTs) represent the gold standard methodological design to evaluate the effectiveness of an intervention in humans but they are subject to bias, including study publication bias and outcome reporting bias. National and international organisations and charities give recommendations for good research practice in relation to RCTs but to date no review of these guidelines has been undertaken with respect to reporting bias. METHODS: National and international organisations and UK based charities listed on the Association for Medical Research Charities website were contacted in 2007; they were considered eligible for this review if they funded RCTs. Guidelines were obtained and assessed in relation to what was written about trial registration, protocol adherence and trial publication. It was also noted whether any monitoring against these guidelines was undertaken. This information was necessary to discover how much guidance researchers are given on the publication of results, in order to prevent study publication bias and outcome reporting bias. RESULTS: Seventeen organisations and 56 charities were eligible of 140 surveyed for this review, although there was no response from 12. Trial registration, protocol adherence, trial publication and monitoring against the guidelines were often explicitly discussed or implicitly referred too. However, only eleven of these organisations or charities mentioned the publication of negative as well as positive outcomes and just three of the organisations specifically stated that the statistical analysis plan should be strictly adhered to and all changes should be reported. CONCLUSION: Our review indicates that there is a need to provide more detailed guidance for those conducting and reporting clinical trials to help prevent the selective reporting of results. Statements found in the guidelines generally refer to publication bias rather than outcome reporting bias. Current guidelines need to be updated and include the statement that all primary and secondary outcomes prespecified in the protocol should be fully reported and should not be selected for inclusion in the final report based on their results

Systematic Review of the Empirical Evidence of Study Publication Bias and Outcome Reporting Bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials

Hautkrankheiten

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