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Biomedical subjects

K Thomsen

Publications and source records attributed to K Thomsen.

At least 19 recordsLinked to original sources
PubMed2006

Club foot: a twin study.

The aetiology of congenital club foot is unclear. Although studies on populations, families and twins suggest a genetic component, the mode of inheritance does not comply with distinctive patterns. The Odense-based Danish Twin Registry contains data on all 73,000 twin pairs born in Denmark over the last 130 years. In 2002 all 46 418 twins born between 1931 and 1982 received a 17-page questionnaire, one question of which was 'Were you born with club foot?' A total of 94 twins answered 'Yes', giving an overall self-reported prevalence of congenital club foot of 0.0027 (95% confidence interval (CI) 0.0022 to 0.0034). We identified 55 complete twin pairs, representing 12 monozygotic, 22 dizygotic same sex (DZss), 18 dizygotic other sex (DZos) and three unclassified. Two monozygotic and 2 DZss pairs were concordant. The pairwise concordance was 0.17 (95% CI 0.02 to 0.48) for monozygotic, 0.09 (95% CI 0.01 to 0.32) for DZss and 0.05 (95% CI 0.006 to 0.18) for all dizygotic (DZtot) twins. We have found evidence of a genetic component in congenital club foot, although non-genetic factors must play a predominant role.

Clubfoot↗
PubMed2004

Methodological aspects of high-frequency ultrasound of skin in children.

BACKGROUND: High-frequency ultrasound of the skin has recently been introduced for assessment of systemic effects in the cutis and subcutis of oral and inhaled glucocorticoids in children. However, the use of high-frequency skin ultrasound in clinical trials is invalidated because important methodological aspects have not been addressed. The aim of the present study was to evaluate inter- and intraobserver, day to day and diurnal variations of measurement of thickness of cutis and subcutis, and the fraction of low echogenic pixels (fLEP) in the cutis and, furthermore, to assess effects of exercise on the cutis and subcutis and variations in subcutaneous thickness between anatomical locations in children with a high-frequency B-mode ultrasound scanning device. METHODS: Three studies were conducted, each including 10 healthy prepubertal children. High-frequency skin ultrasound was performed with the 20 MHz Dermascan C (Cortex Technology, Hadsund, Denmark). In study 1, the same observer performed five consecutive scannings to assess intraobserver variations. In study two different observers performed scannings at 2 h intervals between 08:00 and 20:00 h, whereby interobserver and diurnal variations were assessed. In study 3, the same observer performed scannings in different anatomical locations on five consecutive days, and on one of these days before and after exercise. Thus day-to-day variations and the effect of exercise were assessed. RESULTS: Low inter- and intraobserver variations were found on assessment of the thickness of cutis and subcutis, whereas high variations were found on evaluation of the dermal water content. Diurnal variations were absent, and day-to-day variations were low. Exercise caused significant increases in the thickness of cutis and subcutis on the thigh. CONCLUSION: Low inter- and intraobserver variations make high-frequency ultrasound a precise and reliable tool for assessment of the cutaneous and subcutaneous thickness in children. In future trials, repetitive scannings need not to be performed at the same time of the day, whereas strenuous physical activity should be avoided on days of examination.

Body Water↗
PubMed2004

Lower leg growth suppression caused by inhaled glucocorticoids is not accompanied by reduced thickness of the cutis or subcutis.

BACKGROUND: Exogenous glucocorticoids suppress short-term lower leg growth in children as assessed by knemometry. The knemometric measurements, however, may be confounded by reductions in the thickness of the cutis and subcutis over the knee. AIM: To assess whether inhaled glucocorticoid-induced suppression of short-term growth is accompanied by changes in the thickness of the cutis and subcutis. METHODS: The study was a randomized, controlled, crossover trial with 1 wk treatment, run-in and washout periods. Active treatment was inhaled budesonide 200 microg twice daily. Short-term growth was assessed by knemometry, and the thickness of the cutis and subcutis over the knee, on the volar forearm and abdomen was measured by 20 MHz B-mode ultrasound. MATERIAL: Nineteen children with asthma aged 7 to 13 y. RESULTS: Lower leg growth was significantly reduced during budesonide treatment (0.27 mm/wk) compared to the treatment-free period (0.54 mm/wk) (p = 0.02, 95%: -0.50 to -0.05). Variations in the thickness of the cutis were seen during budesonide treatment (mean +/- SEM): -0.01 +/- 0.03 mm over the knee, -0.02 +/- 0.02 mm on the forearm and 0.01 +/- 0.02 mm on the abdomen. The variations in the total thickness of the cutis and subcutis were -0.05 +/- 0.12 mm, 0.06 +/- 0.12 mm and -0.06 +/- 0.10 mm during budesonide treatment. The variations in thickness of the cutis or subcutis were not statistically different during budesonide treatment and the treatment free period in any anatomical location. CONCLUSIONS: Short-term lower leg growth suppression induced by inhaled glucocorticoids is not confounded by variations in thickness of cutis or subcutis. The present observations further establishes knemometry as a reliable tool for assessment of the risk of growth suppression of inhaled glucocorticoids in children with asthma.

Abdomen↗
PubMed2003

Local sensory ganglion ischemia induced by endothelin vasoconstriction: vulnerability of diabetic neurons and microvessels.

In some disorders of the peripheral nervous system, it is relevant to understand how sensory neurons respond to selective ganglion ischemia. Sensory dorsal root ganglia may be susceptible to ischemic damage and irretrievable neuron loss because of their metabolic requirements. In diabetes, heightened sensitivity to ischemia associated with elevated endothelin levels might render ganglia particularly vulnerable. In this work, we created a model of local sensory ganglion ischemia by generating intense local vasoconstriction from applied endothelin-1 (ET). In this model, we compared relative vulnerability of L5 ganglia microvessels and neurons to ET in streptozotocin-induced diabetic rats and nondiabetic controls. Diabetic ganglia had reductions in baseline core ganglion blood flow (GBF) measured using microelectrode hydrogen clearance polarography and ET induced particularly profound declines. Serial GBF measurements made using a laser Doppler flowmetry probe also indicated that diabetic ganglia exposed to ET had a marked prolongation in its action. Neuron perikarya and proximal axon segments were more vulnerable in diabetes. Neurons exhibited loss of neurofilament labeling, dissolution of the neurons, replacement of neurons with "nests of Nageotte," displacement of nuclei to the periphery of perikarya, and nuclear labeling with TUNEL. Both intraganglionic axons and downstream sural sensory axons developed evidence of axonal degeneration. Local endothelin-induced vasoconstriction of microvessels supplying dorsal root ganglia provides a selective model of ischemia. Diabetic vessels and neurons, exposed to a greater depth and duration of ischemia from endothelin, are especially vulnerable.

Animals↗
PubMed2001

Three-dimensional structure of renal Na,K-ATPase from cryo-electron microscopy of two-dimensional crystals.

The structure of Na, K-ATPase was determined by electron crystallography at 9.5 A from multiple small 2-D crystals induced in purified membranes isolated from the outer medulla of pig kidney. The density map shows a protomer stabilized in the E(2) conformation which extends approximately 65 A x 75 A x 150 A in the asymmetric unit of the P2 type unit cell. The alpha, beta, and gamma subunits were demonstrated in the membrane crystals with Western blotting and related to distinct domains in the density map. The alpha subunit corresponds to most of the density in the transmembrane region as well as the large hydrophilic headpiece on the cytoplasmic side of the membrane. The headpiece is divided into three separated domains, which are similar in overall shape to the domains of the calcium pump of the sarcoplasmic reticulum. One of these domains gives rise to a characteristic elongated projection onto the membrane plane while the putative nucleotide binding and phosphorylation domains form comparatively compact densities in the rest of the cytoplasmic part of the structure. Density on the extracellular face corresponds to the protein part of the beta subunit and is located as an extension of the transmembrane region perpendicular to the membrane plane. The structure of the lipid bilayer spanning part suggests the positions for the transmembrane helix from the beta subunit as well as the small gamma subunit present in this Na,K-ATPase. Two groups of ten helices from the catalytic alpha subunit corresponds to the remaining density in the transmembrane region. The present results demonstrate distinct similarities between the structure of the alpha subunit of Na,K-ATPase as determined here by cryo-electron microscopy and the reported X-ray structure of Ca-ATPase. However, conformational changes between the E(1) and E(2) forms are suggested by different relative positions of cytoplasmatic domains.

Animals↗
PubMed2001

Interobserver and intraobserver agreement of radiograph interpretation with and without pedicle screw implants: the need for a detailed classification system in posterolateral spinal fusion.

STUDY DESIGN: A prospective randomized clinical study in which four observers evaluated radiographs of posterolateral fusion masses. OBJECTIVES: To evaluate the accuracy of radiograph interpretation of the posterolateral spinal fusion mass when using a detailed classification system and to analyze the influence of metallic internal fixation devices on radiologic inaccuracy. SUMMARY OF BACKGROUND DATA: In general, the literature describing the classification criteria used for radiograph interpretation of spinal posterolateral fusion has serious deficiencies. There is a need for a detailed classification system. METHODS: Seventy patients were randomly allocated to receive no instrumentation (n = 36) or Cotrel-Dubousset instrumentation (n = 34) in posterolateral lumbar fusion. All four observers participated in a prestudy discussion and evaluated the radiographs (anteroposterior, lateral) taken at the 1-year follow-up evaluation. The observers scored the radiographs twice (30 days apart). Each level on each side was judged separately. A continuous intertransverse bony bridge involving at minimum one of the two sides indicated a fusion at that level. "Fusion" indicated this quality of fusion at all intended levels. If the fusion was doubtful on both sides of the interspace, the individual case could not be classified as "fused." RESULTS: The mean interobserver agreement was 86% (Kappa 0.53), and the mean intraobserver agreement was 93% (Kappa 0.78). No difference in interobserver and intraobserver agreement was found between patients with and without supplementary pedicle screw fixation. All mean Kappa values were classified as fair or good. The four observers identified a mean fusion rate of 81%. CONCLUSION: It is extremely difficult to interpret radiographic lumbar posterolateral fusion success. Such an assessment needs to be performed by use of a detailed radiographic classification system. The classification system presented here revealed good interobserver and intraobserver agreement, both with and without instrumentation. The classification showed acceptable reliability and may be one way to improve interstudy and intrastudy correlation of radiologic outcomes after posterolateral spinal fusion. Instrumentation did not influence reproducibility but may result in slightly underestimated fusion rates.

Adult↗
PubMed2001

Effects of the somatostatin analogue octreotide on renal function in conscious diabetic rats.

BACKGROUND: Studies performed during the last decade have indicated that growth hormone (GH) and insulin-like growth factors (IGFs) may mediate the early renal changes in diabetes mellitus, i.e. hypertrophy and hyperfiltration. This and other observations have led to the suggestion that GH/IGF inhibitors, such as long-acting somatostatin analogue (e.g. octreotide and lanreotide), may be useful in order to inhibit or prevent development of long-term diabetic complications. METHODS: The present study examined the acute and chronic effects of octreotide on renal function following induction of streptozotocin (STZ)-diabetes in rats. The studies were carried out in conscious, non-fasted diabetic animals. RESULTS: Chronic administration of octreotide for 7 days, from onset of diabetes, prevented the decrease of effective renal vascular resistance (ERVR), and the increases in filtration fraction (FF), glomerular filtration rate (GFR), and absolute proximal tubular fluid reabsorption (APR) induced by diabetes. The renal hypertrophy was only partially prevented. In the acute study, similar changes were observed in effective renal plasma flow (ERPF) and ERVR but FF increased and GFR remained unaltered. CONCLUSIONS: Chronic but not acute treatment with octreotide prevented the renal hyperfiltration caused by diabetes. This effect is most likely due to an increase in afferent arteriolar resistance.

Animals↗
PubMed2001

Effects of growth hormone on renal tubular handling of sodium in healthy humans.

To investigate the mechanisms behind the water- and sodium-retaining effects of growth hormone (GH), we studied the effect of GH on 1) water and sodium homeostasis, 2) the renin-angiotensin-aldosterone system (RAAS), and 3) lithium clearance (C(Li)) with and without concomitant prostaglandin (PG) synthesis inhibition with ibuprofen. GH administration for 6 days induced a significant increase in plasma renin, which was abolished by coadministration of ibuprofen (mU x l(-1) x 24 h(-1): control: 22.4 +/- 4.3; GH: 37.7 +/- 8.8; ibuprofen: 15.2 +/- 3.0; GH + ibuprofen: 19.7 +/- 2.5; ANOVA: P < 0.01). Comparable increments in extracellular volume were seen after 6-day treatment with GH alone and in combination with ibuprofen [liters: control, 19.57 +/- 0.92; GH, 20.80 +/- 1.00 (ANOVA: P < 0.0005); ibuprofen, 19.38 +/- 0.90; GH + ibuprofen, 21.63 +/- 1.37 (ANOVA: P < 0.0005)]. Treatment with GH increased C(Li) and changed the tubular handling of sodium and water. The absolute distal sodium reabsorption was increased, and this was only partially counterbalanced by decreased reabsorption in the proximal tubules. The data demonstrate that GH-induced activation of the RAAS can be blocked by concomitant PG synthesis inhibition and that the tubular effects of GH include increased distal nephron sodium and water reabsorption.

Adult↗
PubMed2001

Role of sodium depletion in acute antidiuretic effect of bendroflumethiazide in rats with nephrogenic diabetes insipidus.

The mechanisms underlying the acute antidiuretic response to bendroflumethiazide (BFTZ; 0.25 mg/h for 3 h) in rats with nephrogenic diabetes insipidus (NDI) was investigated. NDI was induced in conscious chronically instrumented female Wistar rats either by chronic lithium administration (40-60 mmol Li/kg of diet for 4 weeks) or by acute infusion of V2 antagonist OPC-31260 (0.2 mg/h). Renal clearance experiments were performed in conscious rats instrumented with permanent catheters. During experiments total body water content was held constant by i.v. replacement of urine production (V) with 150 mM glucose. One group in addition received i.v. replacement of urinary sodium losses. In both models of NDI, BFTZ-induced antidiuresis was associated with a decrease in the delivery of tubular fluid to the distal nephron, as measured by lithium clearance (C(Li)). Both the antidiuresis and the decrease in C(Li) could be prevented by sodium replacement. BFTZ did not affect distal water handling as measured by V/C(Li). BFTZ did not induce antidiuresis in normal rats with water diuresis. It is concluded that in rats with NDI, thiazide-induced antidiuresis can be entirely explained by a fall in distal delivery of tubular fluid related to sodium depletion. This contrasts the response in rats with central diabetes insipidus, where thiazides in addition increase distal water reabsorption.

Animals↗
PubMed2000

Association between CYP1A2 polymorphism and susceptibility to porphyria cutanea tarda.

Individuals with the most common form of the porphyrias, porphyria cutanea tarda (PCT), are believed to be genetically predisposed to development of clinically overt disease through mutations and polymorphisms in genes associated with known precipitating factors. In this study, we have examined a group of Danish patients with PCT for the presence of the C/A polymorphism in intron 1 of CYP1A2. The results demonstrate that the frequency of the highly inducible A/A genotype is increased in both familial and sporadic PCT. This suggests that inheritance of this genotype is a susceptibility factor in development of PCT.

Cytochrome P-450 CYP1A2↗
PubMed2000

Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases.

The clinical, histological, phenotypic and genotypic features of 21 primary cutaneous B-cell lymphomas (CBCLs) have been investigated. The patients were 13 men and eight women aged 34-91 years (median 67) at diagnosis. Eighteen patients had localized disease, and three had multiple skin lesions at diagnosis. Twelve patients developed cutaneous or extracutaneous recurrences, and five died from malignant lymphoma 7-84 months (median 36) after diagnosis. Histological examination showed features of marginal zone/mucosa-associated lymphoid tissue (MALT)-type lymphoma in 12 cases. Three of these had transformed to diffuse large B-cell lymphoma (DLBCL) in relapse biopsies. The remaining cases were seven primary DLBCLs and two cases tentatively classified as follicle centre cell (FCC) lymphoma. The neoplastic B cells showed similar phenotypes and genotypes in most cases (CD20+, CD79+, CD5-, CD10-, cyclin D1-, bcl-2+, bcl-x-, bax-, t(14;18)-negative). p53 protein was expressed in five cases, and four harboured mis-sense or loss-of-function mutations in the p53 gene. Deletion or promoter region hypermethylation of the p16INK4a gene was detected in two patients with DLBCL. The level of retinoblastoma protein expression and the proliferative fraction were significantly higher in DLBCL (> 50%) than in MALT- or FCC-type lymphomas (< 10%). Features associated with an unfavourable prognosis were the presence of multiple skin lesions at diagnosis, transformation from MALT-type lymphoma to DLBCL, and possibly p16INK4a aberrations. It is concluded that most CBCLs are dissimilar from FCC lymphomas and seem to be more closely related to marginal zone/MALT-type lymphomas. It is also suggested that there are fundamental differences between DLBCL and other histological categories of CBCL, indicating that cutaneous DLBCL is a separate entity with an increased growth potential and genetic features similar to DLBCL originating in other anatomical sites.

Adult↗
PubMed2000

Uroporphyrinogen decarboxylase gene mutations in Danish patients with porphyria cutanea tarda.

Decreased uroporphyrinogen decarboxylase (UROD) activity is a characteristic feature of the most common of the porphyrias, porphyria cutanea tarda (PCT). A subgroup of the clinically overt PCT cases is associated with mutations in the gene encoding UROD and inherited as an autosomal-dominant trait. In this study, DNAs from 53 Danish PCT patients were subjected to genetic analysis for UROD mutations using denaturing gradient gel electrophoresis. Eleven genetic variations, seven of which are possible disease causing, were identified. All but one of these mutations were previously unknown, lending further support to the assumption that PCT is a heteroallelic disease. Only 11% of the examined patients were previously recognized as familial PCT cases. However, possible disease-related UROD mutations were identified in 24% of the examined patients, indicating that genetic analysis of PCT patients may improve differentiation between familial and sporadic PCT cases.

Base Sequence↗
PubMed2000

Nitric oxide synthase activity and expression in experimental diabetic neuropathy.

The changes of nitric oxide synthase (NOS) activity and expression in experimental diabetic neuropathy have not been examined. Increases in ganglia NOS might be similar to those that follow axotomy, whereas declines in endothelial NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels or macrophages. In this work, we studied NOS activity in lumbar dorsal root ganglia (DRG) of rats with both short- and long-term experimental streptozotocin-induced diabetes and correlated it with expression of each of the 3 NOS isoforms. NOS enzymatic activity in DRG increased after 12 months of diabetes. This increase, however, was not accompanied by an increase in neuronal NOS immunohistochemistry or mRNA. Immunohistochemical and RT-PCR studies did not identify changes of eNOS expression in 12-month sciatic nerves or DRG from diabetics. Two-month diabetic DRG had increased eNOS mRNA and there was novel eNOS labeling of capsular DRG and perineurial cells. iNOS mRNA levels were lower in diabetics at both time points in peripheral nerves but were unchanged in DRG. Diabetic ganglia showed an increase in NOS activity not explained by novel NOS isoform synthesis. The increases may compensate for NO "quenching" by endproducts of glycosylation. Declines in iNOS may indicate impaired macrophage function.

Animals↗
PubMed2000

In vivo mechanisms of acetylcholine-induced vasodilation in rat sciatic nerve.

We examined the importance of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and neurogenic activity in agonist-induced vasodilation and baseline blood flow [i.e., nerve microvascular conductance (NMVC)] in rat sciatic nerve using laser Doppler flowmetry. Agonists were acetylcholine (ACh) and 3-morpholinosydnonimine (SIN-1). Vasodilation occurring despite NO synthase (NOS) and cyclooxygenase inhibition and showing dependence on K(+) channel activity was taken as being mediated by EDHF. NOS and cyclooxygenase inhibition with N(omega)-nitro-L-arginine (L-NNA) + indomethacin (Indo) revealed two phases of ACh-induced vasodilation: an initial, transient L-NNA + Indo-resistant vasodilation, peaking at 23 +/- 6 s and lasting 145 +/- 69 s, followed by sustained L-NNA + Indo-sensitive vasodilation. L-NNA alone did not affect sustained ACh-induced vasodilation but decreased baseline NMVC by 55%. In the presence of L-NNA + Indo, the K(+) channel blocker tetraethylammonium (TEA) inhibited transient ACh-induced vasodilation by 58% and reduced baseline NMVC by 25%. SIN-1-induced vasodilation increased fourfold in the presence of L-NNA, whereas the specific guanylyl cyclase inhibitor 1H-(1, 2, 4)oxadiazolo(4,3-alpha)quinoxalin-1-one abolished it. However, in homogenates of rat sciatic nerve, SIN-1-stimulated soluble guanylyl cyclase (sGC) activity was unaffected by L-NNA. TTX affected neither SIN-1- nor ACh-induced vasodilation. In conclusion, ACh-induced vasodilation consisted of two components, the first partially mediated by EDHF and the second by a vasodilatory prostanoid + NO. Baseline NMVC was dependent on NO and EDHF. Although L-NNA enhanced SIN-1-induced vasodilation, it had no effect on sGC-activity.

Acetylcholine↗