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Biomedical subjects

S Nielsen

Publications and source records attributed to S Nielsen.

371 records · Page 21Linked to original sources
PubMedDate not supplied

Standardized mortality in eating disorders--a quantitative summary of previously published and new evidence.

Ten eating disorder (ED) populations were reviewed using the standardized mortality ratio (SMR) presenting new evidence for several studies. In eight of the ten samples, strong evidence (in one sample weak evidence and in one sample no evidence) supports an hypothesis of elevated SMR. We found strong evidence for an increase in SMR for anorexia nervosa (AN), whereas no firm conclusions could be drawn for bulimia nervosa (BN). Bias caused by loss to follow-up was quantified and found non-negligable in some samples (possible increase in SMR from 25% to 240%). We did not find a significant effect of gender or time period on SMR. Survival analysis showed a significant difference among the life-tables for males and females; female risk of death averaged 0.59% per year, whereas all male deaths occurred within the first 2 years after presentation. Weight at presentation had a highly significant effect on SMR, and lower weight at presentation was associated with higher SMR. Age at presentation exerted a significant unimodal effect on SMR; aggregate overall SMR was 3.6 for the youngest age group (< 20 years), 9.9 for those aged 20-29 years, and 5.7 for those aged > or = 30 years at presentation. Length of follow-up had a highly significant inverse effect on SMR; maximal SMR was 30 for female AN patients in the first year after presentation. A statistically significant increase in SMR was documented for at least up to 15 years after presentation. One study indicated a treatment effect on SMR. New evidence on causes of death suggests there are more deaths from suicide and other and unknown causes and fewer deaths related to ED than previously reported. Our findings have both research and clinical implications, with the most important clinical implication being the need for vigorous and well-directed treatment efforts from the initial presentation for treatment. An important research implication is that no single measure of mortality is sufficient; that is, only a combination of different statistics will maximize the available information.

Adult↗
PubMedDate not supplied

The survey: what to expect.

Although your hospital will be surveyed only every two or three years, the results of that survey are vital not only to your hospital, but also to your department. And you need to become involved in the process from the presurvey questionnaire to the on-site visit. And you need to prepare for the next survey the day after the last one.

Accreditation↗
PubMedDate not supplied

Immunolocalization of NBC3 and NHE3 in the rat epididymis: colocalization of NBC3 and the vacuolar H+-ATPase.

In the male reproductive tract, the epididymis plays an important role in mediating transepithelial bicarbonate transport and luminal acidification. In the proximal vas deferens, a significant component of luminal acidification is Na+-independent, and mediated by specific cells that possess apical vacuolar proton pumps. In contrast, luminal acidification in the cauda epididymidis is an Na+-dependent process. The specific apical Na+-dependent H+/base transport process(es) responsible for luminal acidification have not been identified. A potential clue as to the identity of these apical Na+-dependent H+/base transporter(s) is provided by similarities between the transport properties of the epididymis and the mammalian nephron. Specifically, the H+/base transport properties of caput epididymidis resemble the mammalian renal proximal tubule, whereas the distal epididymis and vas deferens have characteristics in common with renal collecting duct intercalated cells. Given the known expression of the Na+/H+ antiporter, NHE3, in the proximal tubule, and of the electroneutral sodium bicarbonate cotransporter, NBC3, in renal intercalated cells, we determined the localization of NHE3 and NBC3 in various regions of rat epididymis. NBC3 was highly expressed on the apical membrane of apical (narrow) cells in caput epididymidis, and light (clear) cells in corpus and cauda epididymidis. The number of cells expressing apical NBC3 was highest in cauda epididymidis. The localization of NBC3 in the epididymis was identical to the vacuolar H+-ATPase. The results indicate that colocalization of NBC3 and the vacuolar H+-ATPase is not restricted to kidney intercalated cells. Moreover, the close association of the two transporters appears to be a more generalized phenomenon in cells that express high levels of vacuolar H+-ATPase. Unlike NBC3, NHE3 was most highly expressed on the apical membrane of all epithelial cells in caput epididymidis, with less expression in the corpus, and no expression in the cauda. These results suggest that apical NBC3 and NHE3 potentially play an important role in mediating luminal H+/base transport in epididymis.

Animals↗
PubMedDate not supplied

The Danish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Danish language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Danish CHAQ-CHQ were fully validated with 3 forward and 3 backward translations. A total of 139 subjects were enrolled: 76 patients with JIA (25% systemic onset, 30% polyarticular onset, 19% extended oligoarticular subtype, and 26% persistent oligoarticular subtype) and 63 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Danish version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Adolescent↗
PubMedDate not supplied

TNF and LT binding capacities in the plasma of arthritis patients: effect of etanercept treatment in juvenile idiopathic arthritis.

BACKGROUND: Etanercept (Enbrel) induces a rapid and sustained decline in disease activity in the majority of patients with refractory juvenile idiopathic arthritis (JIA). For unknown reasons, however, a number of JIA patients fail to respond to this therapy. During this treatment neutralisation of tumour necrosis factor (TNF, previously termed TNF alpha) and lymphotoxin (LT, previously termed TNF beta) may be mediated by etanercept itself as well as by naturally occurring soluble TNF receptors. In light of this, it was of interest to study the total TNF neutralizing capacity in plasma before and during treatment with etanercept. RESULTS: In initial experiments plasma samples from healthy individuals were incubated with etanercept, and spiked with TNF or LT to a final concentration of 1000 pg/mL. Detection of TNF and LT by ELISA was found to be reduced by approximately 50% and 80% respectively, at a concentration of etanercept of 5-500 ng/mL, which is close to the pharmacological plasma concentrations. Plasma samples (n = 80) were then collected from 12 JIA patients (5 with pauciarticular, 5 with polyarticular and 2 with the systemic onset type) during treatment with etanercept (0.4 mg/kg twice weekly) for a period of 20.8 (15.6-23.9) months (median, range). The plasma samples were spiked with LT, and the inhibition of LT detection in ELISA was measured. In samples obtained 3 months after the start of etanercept, the inhibition of LT detection was augmented [72% (60-85)] compared with pre-treatment samples [16% (0.32)] (p = 0.0039). These findings were confirmed in binding assays using radiolabelled TNF. Among patients who responded insufficiently to therapy, reduced LT binding capacity, coinciding with flares of disease activity, was observed. CONCLUSION: We have developed an assay by which LT binding capacity, reflecting the level of free, pharmacologically active etanercept, may be monitored in the blood of patients treated with etanercept. This assay may prove to be useful in guiding dose adjustments in patients with an incomplete response to etanercept.

Adolescent↗
PubMedDate not supplied

Cyclosporine A in juvenile idiopathic arthritis. Results of the PRCSG/PRINTO phase IV post marketing surveillance study.

OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care. METHODS: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease. RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation. CONCLUSION: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.

Antirheumatic Agents↗
PubMedDate not supplied

Expression of cyclin (PCNA) and the phosphoprotein dividin are late obligatory events in the mitogenic response.

Analysis of the overall patterns of gene expression at the polypeptide synthesis level has revealed two S-phase specific, proliferation sensitive nuclear proteins [cyclin (PCNA) and dividin (phosphoprotein)] whose rate of synthesis increases at the G1/S transition border of the cell cycle. All available evidence suggests that expression of these proteins are late obligatory events in the mitogenic response.

Cell Cycle↗
PubMedDate not supplied

Transcellular transport of ferritin in rabbit renal proximal tubules.

The purposes of this study were (1) to determine whether or not transcytosis of protein takes place in vivo in rabbit proximal tubules, using ferritin as a marker, (2) to follow the time course of intracellular transport of ferritin, (3) to study the organelles involved in the sequential intracellular transport of the protein, (4) to compare the intracellular transport in vivo and in vitro, and (5) to compare the intracellular transport in rabbit proximal tubules with transport in rat proximal tubules. Female albino rabbits were prepared for micropuncture, and individual proximal tubules were microinfused with a bolus of cationic ferritin for 2-3 min. The tubules were fixed by perfusion with glutaraldehyde at different time intervals after exposure to ferritin. Ferritin was located in the endocytic vesicles, vacuoles, dense apical tubules and lysosomes including multivesicular bodies, initially in the apical part of the cells, then progressively with time transported to the basal part of the cells. An organelle not previously described represented by small tubulovesicular structures (< 0.05 microns in diameter) also contained ferritin. This organelle was observed either close to large ferritin-loaded vacuoles and sometimes connected to the latter, or scattered throughout the cytoplasm, initially in the apical part of the cell but later found increasingly in the basal part. Small clusters of ferritin particles were found in the basolateral intercellular spaces. After 15 min, only small amounts were observed but the number of clusters increased with time after ferritin infusion. No ferritin particles were observed in the Golgi region.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Interleukin-1 receptor antagonist in neonates, children and adults, and in patients with pauci- and polyarticular onset juvenile chronic arthritis.

OBJECTIVE: The production of interleukin (IL) -1 alpha IL-1 beta and IL-1 receptor antagonist (IL-1ra) by blood mononuclear cells (MNC), as well as the corresponding serum levels of IL-1ra were examined in blood samples from umbilical cords (n = 11), children (n = 40) and adults (n = 20), and in 42 patients with juvenile chronic arthritis (JCA) of the pauci- or polyarticular onset type. RESULTS: IL-1ra serum levels were found to differ significantly between the three age groups, being higher in neonates (569 pg/ml) than in children (70 pg/ml) and adults (177 pg/ml). IL-1ra production in E. coli lipopolysacharide (LPS) stimulated-cultures of MNC was also significantly higher in neonates (median 2451 pg/ml) than in children (1526 pg/ml), but similar to that in adults (2107 pg/ml). IL-1ra levels in the sera of both subgroups of JCA patients were significantly elevated (median 257 pg/ml), but did not reflect paraclinical or clinical disease parameters. In samples of synovial fluid the IL-1ra levels tended to be fairly high, up to approximately 2 ng/ml, but they did not reflect the serum levels of IL-1ra. CONCLUSION: These findings suggests that the upregulation of IL-1ra production forms part of the immunoregulatory response in JCA patients, and that the insufficient production of IL-1ra is unlikely to contribute to the pathogenesis of JCA.

Adolescent↗
PubMedDate not supplied

Disordered water channel expression and distribution in acquired nephrogenic diabetes insipidus.

A series of recent studies have demonstrated that expression of aquaporin-2 (AQP2), the vasopressin-regulated water channel of the kidney collecting duct, is greatly reduced in acquired forms of nephrogenic diabetes insipidus (NDI). In some forms of NDI, there is also impaired delivery of these channels to the apical plasma membrane, where they permit water reabsorption from the urine. The combination of these factors is likely to underlie the urinary concentrating defect that defines these conditions. Direct infusion of vasopressin causes an increase in AQP2 expression, probably via a rise in cytosolic adenosine 3:5-cyclic phosphate, which also acts as the second messenger, triggering the delivery of AQP2 to the plasma membrane. However, it is clear from the studies described that there are also vasopressin-independent pathways that regulate the expression of AQP2, some of which appear to reflect intranephric changes, whereas others involve systemic signals. These studies also show that recovery of AQP2 expression, even after correction of the underlying condition, can be slow, consistent with the clinical observation that recovery of urinary-concentrating ability often takes weeks or months. An understanding of the cellular signals and mechanisms responsible for the decrease in AQP2 expression may make it possible to develop treatments for this common clinical problem.

Animals↗