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Biomedical subjects

T Jensen

Publications and source records attributed to T Jensen.

At least 19 recordsLinked to original sources

Increasing incidence of childhood tumours of the central nervous system in Denmark, 1980-1996.

The registered incidence rate of childhood central nervous system (CNS) tumours has increased in several countries. It is uncertain whether these increases are biologically real or owing to improved diagnostic methods. We explored the medical records of 626 CNS tumours diagnosed in Danish children between 1980 and 1996. Population-based registers were used to extract data on mortality and background population. Temporal patterns were analysed by regression techniques. Most tumours were verified by computed tomography (78%) or magnetic resonance imaging (14%). Overall, the incidence rate increased by 2.9% per year (95% confidence interval (CI): 1.3;4.5) and the mortality rate increased by 1.4% per year (95% CI: -0.4;3.3). Among children aged 0-4 years, the survival rate after diagnosis remained almost unchanged, whereas among children aged 5-14 years, the 10-year survival rate improved from 59 to 74%. These data suggest that the incidence rate of CNS tumours among Danish children has truly increased, although alternative explanations cannot be excluded.

Adolescent↗

Deformation of the mandible due to neonatal moulding: a 10-year follow-up.

A 3-day-old infant with paralysis of the marginal mandibular branch of the facial nerve and asymmetry of the mandible due to neonatal moulding is presented. Ten years after the initial presentation, the asymmetry and paralysis was still present. Orthodontic treatment has been instituted because of malocclusion. Surgical correction of the mandibular asymmetry after adulthood seems not to be necessary.

Facial Asymmetry↗

Comparison of dual X-ray absorptiometry (DXA), digital X-ray radiogrammetry (DXR), and conventional radiographs in the evaluation of osteoporosis and bone erosions in patients with rheumatoid arthritis.

OBJECTIVE: To compare the relationship between bone mineral density (BMD) in the metacarpal bones and forearm measured by dual X-ray absorptiometry (DXA) and digital X-ray radiogrammetry (DXR) and radiological alterations in patients with early and established rheumatoid arthritis (RA). PATIENTS AND METHODS: In each of the three disease duration groups, 11 female RA patients were included. The patients were further divided into two groups according to bone erosions. BMD in the metacarpals was evaluated by DXA and DXR. RESULTS: A significant relationship between DXA-BMD and DXR-BMD was observed. DXR-BMD and the individually combined cortical thickness (CT) of the metacarpo-phalangeal (MCP) joints were related to disease duration and erosions. Patients with erosive disease had lower values of age- and sex-adjusted BMD measured with DXA, but most significantly with DXR. CONCLUSION: DXR appears to be a more sensitive method than DXA in detecting early bone loss in patients with RA. The relationship of DXR-BMD to disease duration and bone damage indicates that the DXR method may be useful in the evaluation of disease activity and progression.

Absorptiometry, Photon↗

Elevated plasma beta-endorphin/beta-lipotropin concentration following a radius fracture.

Plasma beta-endorphin/beta-lipotropin concentration was assessed soon after a fracture. Blood samples from 14 patients with radius fractures were obtained from both arms soon after admission to the hospital (mean 245 min) after the accident. Follow-up samples were taken after healing of the fractures. Higher plasma beta-endorphin/beta-lipotropin concentrations were found in blood samples taken soon after a fracture in both arms compared with the concentrations after healing of the fracture. At admission, mean beta-endorphin/beta-lipotropin concentrations in the fractured and the contralateral arms were 12.7 pmol/L and 13.2 pmol/L, and after recovery 11.1 pmol/L and 11.5 pmol/L (p = 0.012 and p = 0.041), respectively. The pain decreased according to the visual analogue scale (VAS) (0-10) from 4.64 at admission to 0.58 after healing (p < 0.001). In conclusion, this study showed that beta-endorphin/beta-lipotropin concentrations are increased in both arms following a radius fracture compared to the level after the fracture has healed.

Adult↗

Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome.

OBJECTIVE: To compare changes in regional bone mineral density (BMD) of the metacarpal joints measured by dual x ray absorptiometry (DXA) and digital x ray radiogrammetry (DXR) in relation to disease activity and radiographic outcome in a two year follow up study of patients with early RA and unclassified polyarthritis. PATIENTS AND METHODS: 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least four weeks and less than two years were included. 51 patients fulfilled the ACR criteria for RA. 21 patients had unclassified polyarthritis. The patients with RA were divided into groups according to mean disease activity, average glucocorticoid dose, and MRI and x ray detected bone erosions in the hands. Clinical and biochemical measurements were made every month and an x ray examination of the hands and BMD of the metacarpal joints every six months. RESULTS: DXR BMD decreased significantly only in patients with RA from month 6 and was associated with the mean disease activity. Patients with RA and erosive as well as non-erosive disease showed a significant decrease in the rate of bone loss, greatest in those with erosive disease. No changes in BMD measured by DXA were seen in any patient group. CONCLUSION: DXR is a useful measure of the destructive disease activity in patients with RA and unclassified polyarthritis, providing valuable information about bone changes associated with disease activity and erosive disease in early RA. DXR is better than DXA for detecting and monitoring periarticular osteoporosis of the metacarpal bone.

Absorptiometry, Photon↗

Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes.

OBJECTIVE: Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus. However, fish oil may have deleterious effects on lipid peroxidation and glycemic control. DESIGN: In this study, 44 type 2 diabetic patients were randomized to vitamin E standardized (53.6 mg/day) supplementation (capsules) with 4 g daily of either fish oil (n=23) or corn oil (n=21) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation. LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu(2+). As a marker of in vivo oxidation malondialdehyde concentration in LDL (LDL-MDA) was measured. RESULTS: Fish oil reduced both mean lag time (before, 57.8; after, 48.8 min, P<0.001) and mean propagation rate (before, 0.018 DeltaOD/min; after, 0.015 DeltaOD/min, P<0.001), whereas corn oil had no influence on lag time and propagation rate. The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment. LDL-MDA changes differed borderline significantly between groups (FO, 110.4 pmol/mg protein; CO, 6.7 pmol/mg protein; P=0.057). Fish oil supplementation had no influence on glycemic control as assessed from HbA(1c) and fasting blood glucose. CONCLUSION: According to our findings, fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles. More studies are needed to clarify the clinical importance of this finding.

Adult↗

Staining of celiac disease-relevant T cells by peptide-DQ2 multimers.

Gluten-specific T cells in the small intestinal mucosa are thought to play a central role in the pathogenesis of celiac disease (CD). The vast majority of these T cells recognize gluten peptides when presented by HLA-DQ2 (DQA1*05/DQB1*02), a molecule which immunogenetic studies have identified as conferring susceptibility to CD. We have previously identified and characterized three DQ2-restricted gluten epitopes that are recognized by intestinal T cells isolated from CD patients, two of which are immunodominant. Because almost all of the gluten epitopes are restricted by DQ2, and because we have detailed knowledge of several of these epitopes, we chose to develop peptide-DQ2 tetramers as a reagent to further investigate the role of these T cells in CD. In the present study, stable soluble DQ2 was produced such that it contained leucine zipper dimerization motif and a covalently coupled peptide. We have made four different peptide-DQ2 staining reagents, three containing the gluten epitopes and one containing a DQ2-binding self-peptide that provides a negative control for staining. We show in this study that peptide-DQ2 when adhered to plastic specifically stimulates T cell clones and that multimers comprising these molecules specifically stain peptide-specific T cell clones and lines. Interestingly, T cell activation caused severe reduction in staining intensities obtained with the multimers and an Ab to the TCR. The problem of TCR down-modulation must be taken into consideration when using class II multimers to stain T cells that may have been recently activated in vivo.

Baculoviridae↗

Radically altered T cell receptor signaling in glycopeptide-specific T cell hybridoma induced by antigen with minimal differences in the glycan group.

A T cell hybridoma raised against the synthetic glycopeptide T(72)(Tn) was used to study whether the initial TCR signaling events are markedly different when the hybridoma is stimulated with glycopeptides closely related to the cognate glycopeptide antigen. T(72)(Tn) has an alpha-D-GalNAc group O-linked to the central threonine in the decapeptide VITAFTEGLK, and the hybridoma is known to be highly specific for this carbohydrate group. T(72)(Tn)-pulsed APC induced tyrosine phosphorylation of the TCR-zeta 21- and 23-kDa proteins and the downstream p42/44 MAP kinase and strong IL-2 secretion. APC pulsed with T(72)(alpha-D-GlcNAc), which differs from T(72)(Tn) solely by the orientation of a hydroxy group in the carbohydrate structure, completely failed to induce detectable tyrosine phosphorylation and IL-2 secretion. APC pulsed with S(72)(Tn), which differs from T(72)(Tn) by not having a methyl group in the serine amino acid side chain to which the glycan is attached, induced partial tyrosine phosphorylation of the TCR-zeta 21-kDa protein, no tyrosine phosphorylation of the MAP kinases and no IL-2 production. Molecular modeling of the MHC/glycopeptide complex revealed that the dramatic difference between the stimulatory power of T(72)(Tn) and T(72)(alpha-D-GlcNAc) is mainly due to very small differences in the TCR exposed carbohydrate structure.

Cell Line↗

Stillbirth and neonatal mortality due to congenital anomalies: temporal trends and variation by small area deprivation scores in England and Wales, 1986-96.

We investigated the variation of stillbirth and neonatal mortality due to congenital anomalies in relation to small-area measures of deprivation in a population-based study in England and Wales, 1986-96. We found 10 954 stillbirths and neonatal deaths from all non-chromosomal and chromosomal anomalies during the study period out of a total of 7 487 007 live and stillbirths. The extended perinatal mortality rate (EPM rate) (defined as babies who were stillborn or died within 28 completed days after birth per 10 000 total live and stillbirths) for all chromosomal and all non-chromosomal anomalies was 1.5/10 000 and 13.2/10 000, respectively, over the whole period. The rate for non-chromosomal anomalies halved over the decade while the rate for chromosomal anomalies remained unchanged. The relative risks of EPM for chromosomal and non-chromosomal anomalies were 0.71 [0.80, 0.95] and 1.17 [95%CI 1.06, 1.30], respectively, in the group of wards with highest deprivation compared with the least deprived group. Increasing gradients of EPM with increasing deprivation were observed for (1) grouped non-chromosomal anomalies including neural tube defects, all renal and urinary anomalies, all musculoskeletal anomalies, and multiple anomalies, and (2) several specific non-chromosomal anomalies including anencephaly, limb reduction defects, diaphragm and abdominal wall defects. This study provides strong evidence that increased deprivation is associated with increased EPM due to most non-chromosomal anomalies; the finding of decreased relative risk for chromosomal anomalies is probably related to differences in maternal age distribution between deprivation groups.

Chromosome Aberrations↗

Implantable cardioverter defibrillator in a 4-month-old infant with cardiac arrest associated with a vascular heart tumor.

A previously healthy male infant was resuscitated after spontaneous ventricular fibrillation at 9 weeks of age. Echocardiography revealed three tumors in the left ventricle not amenable to complete resection. Despite treatment with antiarrhythmic agents the ventricular arrhythmias continued. When the child was 4 months old and weighed 7 kg an ICD system was implanted using epicardial sense-pacing leads and a superior vena caval lead as a subcutaneous defibrillator coil placed posterior on the left thorax. Shocks were delivered between the subcutaneous coil lead and the intraabdominally placed ICD can. This ICD array system has not been reported previously.

Defibrillators, Implantable↗

Lack of effect of fish oil supplementation on coagulation and transcapillary escape rate of albumin in insulin-dependent diabetic patients with diabetic nephropathy.

OBJECTIVE: We studied the effect of a diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy in order to evaluate whether abnormal transcapillary escape rate of albumin and procoagulant activity in these patients could be modified. METHODS: A double-blind, randomized, controlled study was carried out at a tertiary referral centre. The subjects were 29 insulin-dependent diabetic patients with nephropathy. One year of fish oil supplementation (4.6 g n-3 fatty acids/day) was compared with placebo (olive oil). The main outcome measures were N-3 fatty acid proportions of platelet lipids, transcapillary escape rate of albumin, prothrombin fragment 1 + 2, thrombin-antithrombin complexes, markers of fibrinolysis, fibrinogen, factor VII antigen and activity, thrombomodulin, von Willebrand factor, platelet factor 4 and beta-thromboglobulin. These were measured every 6 months. RESULTS: Neither transcapillary escape rate of albumin (7.4 (median) (5.0-9.8) (range) % vs. 7.0 (4.6-10.6) %) nor prothrombin fragment 1 + 2 (0.97 (0.72-2.40) nmol/L vs. 1.01 (0.59-3.11) nmol/L) changed after 12 months of fish oil supplementation. CONCLUSION: Increased transcapillary escape rate of albumin and activity could not be modified during diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy.

Antithrombin III↗

Preventing diabetic nephropathy: an audit.

In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary albumin excretion rate (AER) of 6% to 14%/year and a risk for the development of diabetic nephropathy of 3% to 30%/year have previously been reported. The aim of the present study was to audit the effect of angiotensin converting enzyme (ACE) inhibition on the progression of microalbuminuria and development of diabetic nephropathy. We consecutively identified 227 type 1 diabetic patients with persistent microalbuminuria (urinary AER between 30 and 300mg/24h, ELISA). According to the level (> or = 100 or < 100mg/24 h) and/or rate of progression in urinary AER (>6% or < or =6%/year), patients were divided into a high-risk group (n= 177) and a low-risk group (n= 50) for development of diabetic nephropathy. According to international guidelines, all patients at high-risk were recommended ACE-inhibitor treatment. Throughout the study, 67% of the patients were treated with an ACE inhibitor. Urinary AER significantly declined by 8.3%/year (95% CI: 2.8 to 13.9) in the whole group of patients, and the risk for the development of diabetic nephropathy during follow-up was 3.5%/year. Glycaemic control and blood pressure remained unchanged during the study. The implementation of modified international guidelines regarding the use of ACE inhibition in the treatment of microalbuminuric type 1 diabetic patients reduced progression to diabetic nephropathy comparable to what has previously been reported in intervention trials.

Albuminuria↗

Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment.

OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow-acting-anti-rheumatic-drugs (SAARDs) +/- GC, the PTH secretion and calcium set point were evaluated by use of the Cica clamp technique before and after 1 month of treatment. RESULTS: S-osteocalcin, s-total alkaline phosphatase (s-TAP) and s-carboxyterminal cross-linked telopeptide of type I collagen (s-ICTP) were elevated in all groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease activity. In the subgroups undergoing the Cica clamp technique, no difference in PTH responsiveness of B-Ca2+ was unveiled. CONCLUSION: Neither active disease nor GC therapy appears to induce secondary hyperparathyroidism, nor is there an alteration in PTH responsiveness of B-Ca2+ in patients with RA. The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.

Anti-Inflammatory Agents↗

Effects of marked hyperthermia with and without dehydration on VO(2) kinetics during intense exercise.

This study determined whether marked hyperthermia alone or in combination with dehydration reduces the initial rate of rise in O(2) consumption (VO(2) on-kinetics) and the maximal rate of O(2) uptake (VO(2 max)) during intense cycling exercise. Six endurance-trained male cyclists completed four maximal cycle ergometer exercise tests (402 +/- 4 W) when euhydrated or dehydrated (4% body wt) with normal (starting esophageal temperature, 37.5 +/- 0.2 degrees C; mean skin temperature, approximately 31 degrees C) or elevated (+1 and +6 degrees C, respectively) thermal strain. In the euhydrated and normal condition, subjects reached VO(2 max) (4.7 +/- 0.2 l/min) in 228 +/- 34 s, with a mean response time of 42 +/- 2 s, and fatigued after 353 +/- 39 s. Hyperthermia alone or in combination with dehydration reduced mean response time (17-23%), VO(2 max) (16%), and performance time (51-53%) (all P < 0.01) but did not alter the absolute response time (i.e., the time to reach 63% response in the control trial, 3.2 +/- 0.1 l/min, 42 s). Reduction in VO(2 max) was accompanied by proportional decline in O(2) pulse and significantly elevated maximal heart rate (195 vs. 190 beats/min for hyperthermia vs. normal). Preventing hyperthermia in dehydrated subjects restored VO(2 max) and performance time by 65 and 50%, respectively. These results demonstrate that impaired high-intensity exercise performance with marked skin and internal body hyperthermia alone or in combination with dehydration is not associated with a diminished rate of rise in VO(2) but decreased VO(2 max).

Adult↗

Expression and function of brain-derived neurotrophin factor and its receptor, TrkB, in ovarian follicles from the domestic hen (Gallus gallus domesticus).

This report summarizes patterns of mRNA expression for the brain-derived neurotrophic factor (BDNF) together with its high-affinity neurotrophin receptor trkB within the hen ovary during follicle development, describes hormonal mechanisms for the regulation of trkB gene expression and provides preliminary evidence for a novel function for BDNF-mediated TrkB signaling within the granulosa layer. Levels of BDNF mRNA in the thecal layer and of trkB mRNA within the granulosa cell layer increase coincident with entrance of the follicle into the preovulatory hierarchy. Localization of the BDNF mRNA transcript correlates with expression of BDNF protein within the theca interna of preovulatory follicles, while localization of trkB mRNA and protein occurs extensively within the granulosa cell layer of preovulatory follicles. This pattern of expression suggests a paracrine relationship between theca and granulosa cells for BDNF signaling via TrkB. Vasoactive intestinal peptide and gonadotropin treatments stimulate increases in levels of trkB mRNA within cultured granulosa cells derived from both prehierarchal and preovulatory follicles, and this response is increased by co-treatment with 3-isobutyl-1-methylxanthine. Finally, BDNF treatment of cultured granulosa cells from preovulatory follicles results in a modest, but significant, reduction in basal progesterone production, whereas this effect was reversed by k252a, an inhibitor of Trk kinase activity. These results support the proposals that BDNF functions as a paracrine signal in hen granulosa cells and that its physiological functions may include the modulation of steroidogenesis.

Animals↗

The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis. TIRA Group.

OBJECTIVE: To determine whether variant alleles of the mannose binding lectin (MBL) gene causing low serum concentrations of MBL are associated with increased susceptibility to rheumatoid arthritis (RA) and erosive outcome in an inception cohort of patients with early polyarthritis. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 68 Danish patients with incident early polyarthritis observed for one year. The associations between MBL and specific HLA-DRB1 genotypes and disease outcomes were analyzed. RESULTS: Among the patients with early polyarthritis 7.4% (5/68) and 41.2% (28/68) were homozygous and heterozygous for MBL variant alleles, compared with 2.8% (7/250) and 34.4% (86/250) of healthy controls (p = 0.09), while the corresponding figures in the patients with RA were 10% (5/50) and 42% (21/50) (p = 0.03), and in the patients with erosive RA 18.8% (3/16) and 35.3% (6/16), respectively (p = 0.004). Patients with early polyarthritis homozygous for MBL variant alleles had an increased risk of having erosive RA at inclusion by a factor of 4.7 (p = 0.02) and after one year by a factor of 3.6 (p = 0.04). MBL deficiency was associated with increased levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) at inclusion (p < 0.05). HLA-DRB1 alleles were not found to be associated with disease outcome. CONCLUSION: MBL variant alleles appear to be weak susceptibility markers for RA, and patients with early polyarthritis and homozygous for MBL structural variant alleles have a higher risk of developing early erosive RA. These findings, together with the positive association between MBL variant alleles and the increased serum levels of IgM RF and CRP, point at the MBL gene as a relevant locus in the pathophysiology of RA.

Adult↗