Health-related quality of life in patients with chronic rheumatic disease after a multidisciplinary rehabilitation regimen.

INTRODUCTION: Multidisciplinary rehabilitation has beneficial effects on health-related quality of life (HRQoL) in patients with chronic rheumatic diseases. However, whether this intervention benefits different age groups in women or men is largely unknown. PURPOSE: To investigate HRQoL in patients with chronic rheumatic disease after completion of a 3-week multidisciplinary treatment, with special focus on differences in effect between age and gender groups. METHOD: HRQoL was measured with SF-36. Mean scores for all SF-36 domains were compared before and after the 3-week regimen and again at 3-, 6-, and 12-month follow-ups. Multivariable linear regression models using generalized estimating equations to account for repeated measurement were employed. A weighting procedure to account for differential dropouts was applied. RESULTS: Three hundred fifty-six women and 74 men with chronic rheumatic disease were included. There were short-term improvements in all SF-36 domains irrespective of age or gender. These effects persisted for up to 1 year in the psychological, social, and energy domains for women under 50. We found no lasting effects for men; however, young men showed similar trends. CONCLUSION: Inpatient multidisciplinary rehabilitation improves short-term HRQoL in all patients. Younger women maintain these beneficial effects for up to 1 year. Additional intervention should be considered for elderly women and for men in order to sustain rehabilitation effects.

Did Philippe Pinel frame the concept of the disease rheumatoid arthritis in the year 1800?

The dissertation from 1800 by Landré-Beauvais (LB) is quoted as an early description of rheumatoid arthritis (RA) with the implication that the disease was new at that time. However, physicians of the past may not have been able to perceive an already existing disease due to a lacking concept of it. The dissertation has been studied in the context of contemporary medical literature, modern historical and biographical texts. LB's dissertation seems to have been influenced by LB's mentor Philippe Pinel. The present study does not permit to conclude whether RA was a new disease.

A 3-year physical activity intervention program increases the gain in bone mineral and bone width in prepubertal girls but not boys: the prospective copenhagen school child interventions study (CoSCIS).

The aim of this study was to evaluate the effect of increasing the amount of time spent in physical education classes on bone mineral accrual and gain in bone size in prepubertal Danish children. A total of 135 boys and 108 girls, aged 6-8 years, were included in a school-based curriculum intervention program where the usual time spent in physical education classes was doubled to four classes (180 min) per week. The control group comprised age-matched children (62 boys and 76 girls) recruited from a separate community who completed the usual Danish school curriculum of physical activity (90 min/week). Dual-energy X-ray absorptiometry was used to evaluate bone mineral content (BMC; g), bone mineral density (g/cm(2)), and bone width at the calcaneus and distal forearm before and after 3 years of intervention. Anthropometrics and Tanner stages were evaluated on the same occasions. General physical activity was measured with an accelerometer worn for 4 days. In girls, the intervention group had a 12.5% increase (P = 0.04) in distal forearm BMC and a 13.2% increase (P = 0.005) in distal forearm scanned area compared with girls in the control group. No differences were found between the intervention and control groups in boys. Increasing the frequency of physical education classes for prepubertal children is associated with a higher accrual of bone mineral and higher gain in bone size after 3 years in girls but not in boys.

Peripheral bone mineral density and different intensities of physical activity in children 6-8 years old: the Copenhagen School Child Intervention study.

This study aimed to evaluate the association between objectively measured habitual physical activity and calcaneal and forearm bone mineral density (BMD, g/cm(2)), one mechanically more loaded and one less loaded skeletal region, in children aged 6-8 years. BMD was measured in 297 boys and 265 girls by peripheral dual-energy X-ray absorptiometry in the forearm and calcaneus. An accelerometer registered the level of physical activity during 4 days (2 weekdays and the weekend). Weight, height, and skinfold thickness were measured. In order to establish thresholds (count . min(-1)) for bone-stimulating physical activity, we evaluated different definitions of vigorous physical activity. The boys had 3.2% higher distal forearm bone mineral content (BMC, P < 0.001) and 4.5% higher distal forearm BMD (P < 0.001) than the girls. They also carried out 9.7% more daily physical activity and spent 14.6-19.0% more time in vigorous physical activity (all P < 0.05) compared to the girls. In contrast, the girls had 3.8% higher calcaneal BMC (P < 0.01) and 2.5% higher calcaneal BMD (P < 0.05) than the boys. Both calcaneal and forearm BMD were significantly related to total time of daily physical activity as well as with intense physical activity above all the chosen cut-off points (all P < 0.05). The beta value for mean count . min(-1) physical activity was significantly lower than that for all the chosen cut-off points of vigorous activity both for calcaneal and distal forearm BMD. This study suggests that both habitual daily physical activity and amount of vigorous physical activity in children aged 6-8 years are associated with appendicular BMD.

Sex differences in bone size and bone mineral density exist before puberty. The Copenhagen School Child Intervention Study (CoSCIS).

BACKGROUND: The aim of this study was to provide normative data of bone mineral density (BMD; g/cm(2)) of the forearm and the calcaneus, evaluated by peripheral dual X ray absorbtiometry (DXA), in children aged 6 to 7 years of age and to evaluate the association with anthropometrics and sex. MATERIAL AND METHODS: 368 boys and 326 girls with a mean age of 6.7 +/- 0.4 years participated. BMD was measured by DXA in the forearms and the os calcanei, with average values presented in this report. Measurements of weight, height, skinfolds, the width of distal radius and ulna, and the femur condyles were collected and body composition estimated from skinfolds measurements. RESULTS: There was no difference in calcaneus BMD when comparing boys and girls, whereas the boys had 4.5% (0.013 g/cm(2)) higher forearm BMD than the girls (P < 0.001). Calcaneal BMD (mean 0.318 g/cm(2)) was 11% higher than forearm BMD (mean 0.283 g/cm(2)). Linear relationship was found between calcaneus BMD and weight (partial r = 0.50), Fat free mass (FFM) (partial r = 0.50), Fat mass (FM) (partial r = 0.45), % body fat (partial r = 0.29) and knee width (partial r = 0.46), all P < 0.000 respectively. Adjusted for weight the relationship between calcaneus BMD and FFM, FM, %body fat and knee width disappeared. There were significant relationships between the forearm BMD and weight (partial r = 0.37), FFM (partial r = 0.39), FM (partial r = 0.28), %body fat (partial r = 0.14) and wrist width (partial r = 0.24), all P < 0.000 respectively. Adjusted for body weight, the relationship remained between forearm BMD and FFM (r = 0.10), FM (R = -0.10) and % body fat (r = -0.12), all P < 0.000 respectively. Children measured in the spring had 3.5% (P < 0.01) higher calcaneus BMD than children measured in the winter. CONCLUSION: Seven year old boys have higher BMD in the forearm but not in the calcaneus in comparison with girls of a similar age. Body weight is the best predictor of calcaneus BMD, accounting for 25% of the variance whereas body weight and FFM are the best predictors of forearm BMD, each accounting for 17% of the variance, respectively.

Physical fitness and physical activity during adolescence as predictors of cardiovascular disease risk in young adulthood. Danish Youth and Sports Study. An eight-year follow-up study.

The purpose of this study was to determine if physical activity, aerobic fitness and isometric strength during adolescence were predictors of cardiovascular risk factor levels in young adulthood. The following measurements were carried out: maximal oxygen uptake (VO(2)max), maximal voluntary contraction (MVC) in four muscle groups, physical activity (questionnaire), blood pressure (BP), total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, anthropometric variables and body fat % (sum of four skinfolds). The data were collected from the Danish Youth and Sports study, an observational longitudinal study in which two measurements were carried out over an eight-year period. The findings in this study indicated that the relationships between the absolute levels of physical fitness and activity in adolescence and the subsequent level of CVD risk factors are weak. However, the changes in physical fitness and physical activity were related to the absolute levels of CVD risk factors in young adulthood, especially in men. Weak relationships were found between the changes in physical fitness/activity and changes in CVD risk factor levels in both sexes. In conclusion, many subjects changed their levels of physical activity and physical fitness between adolescence and young adulthood and the changes, especially in aerobic fitness, seemed to be the best predictor of CVD risk factor levels in young adulthood.

Arginine residue 120 of the human GABAA receptor alpha 1, subunit is essential for GABA binding and chloride ion current gating.

The effect of mutating the conserved amino acid residue arginine 120 to lysine in the GABAA receptor alpha 1 subunit was studied. In electrophysiological experiments, the arginine 120 lysine (R120K) mutation in the alpha 1 subunit, when co-expressed with beta 2 and gamma 2 subunits in Sf-9 insect cells, induces a 180-fold rightward shift of the GABA dose-response curve compared with wild type alpha 1 beta 2 gamma 2s GABAA receptors. The diazepam potentiation of GABA-gated chloride ion currents was not affected. The binding of the GABAA ligands [3H]muscimol and [3H]SR 95531 to alpha 1 (R120K) beta 2 gamma 2s GABAA receptors was abolished but the binding affinity of the benzodiazepine receptor ligand [3H]flunitrazepam was unchanged. These results suggest that the arginine residue 120 in the alpha 1 subtype of the GABAA receptor is essential for GABA binding.

[CT-guided spinal biopsy in spondylodiscitis]. / CT-vejledt borebiopsi ved spondylodiscitis.

Since February 1987 percutaneous CT-guided spine biopsy was performed in 18 patients with spondylodiscitis at the X-ray Department of Bispebjerg Hospital. Eleven cases were spontaneous and seven followed spinal surgery. The infection was located in five cases in the thoracic spine and in 13 cases in the lumbar spine. Only one biopsy was performed during general anaesthesia, the rest under local anaesthesia. No complications were observed. The bioptic material was cultivated immediately beside the patient and incubated for 14 days. The infective organism was isolated in 12 cases (67%). Thus, material obtained through a fine needle was satisfactory for microbiological investigation. A biopsy is crucial for establishing a microbiological diagnosis and thereby enabling prompt adequate treatment.

[Spontaneous and postoperative spondylodiscitis. A material concerning 23 patients]. / Spontan og postoperativ spondylodiscitis. Et materiale på 23 patienter.

A retrospective study of 23 patients with spondylodiscitis is reported. Sixteen cases were spontaneous. Five of these were seen in the acute phase with S. aureus grown from the blood. Eleven patients were investigated with CT-guided biopsy of the spine with identification of different microorganisms in eight cases. In four of seven cases of spondylodiscitis after operation for disc herniation coagulase-negative staphyloccoci were grown after CT-guided biopsy. In spontaneous cases pain disappeared and CRP was normalized within a few weeks after treatment with antibiotics, but radiological changes might progress for several months. Antibiotics were given for two to six months, with a mean of 5.1 months in purulent bacterial infections, and all patients were considered cured after this.

Effects of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial agonist, on recombinant human GABA(A) receptors.

gamma-Aminobutyric acidA (GABA(A)) gated chloride ion channels were expressed from human recombinant cDNA using the baculovirus/Sf-9 insect cell expression system. The electrophysiological effects in whole-cell currents of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial agonist, were investigated on GABA(A) receptor complexes of alpha1beta2gamma2S subunits as well as a slightly modified construct of alpha1(valine 121)beta2gamma2S subunits. Here we report that (1)4-PIOL induces an inward whole-cell current in a concentration-dependent manner in both alpha1(val 121)beta2gamma2S and alpha1(ile 121)beta2gamma2S receptor subunit combinations. (2) The 4-PIOL induced whole-cell currents were more pronounced in alpha1(val 121)beta2gamma2S than in alpha1(ile 121)beta2gamma2S receptor subunit combinations. (3) 4-PIOL inhibited GABA-induced responses on alpha1(ile 121)beta2gamma2S and alpha1(val 121)beta2gamma2S receptor combinations with similar potency.

Decreased agonist sensitivity of human GABA(A) receptors by an amino acid variant, isoleucine to valine, in the alpha1 subunit.

Recombinant human GABA(A) receptors were investigated in vitro by coexpression of cDNAs coding for alpha1, beta2, and gamma2 subunits in the baculovirus/Sf-9 insect cell system. We report that a single amino acid exchange (isoleucine 121 to valine 121) in the N-terminal, extracellular part of the alpha1 subunit induces a marked decrease in agonist GABA(A) receptor ligand sensitivity. The potency of muscimol and GABA to inhibit the binding of the GABA(A) receptor antagonist [3H]SR 95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide) was higher in receptor complexes of alpha1(ile 121) beta2gamma2 than in those of alpha1(val 121) beta2gamma2 (IC50 values were 32-fold and 26-fold lower for muscimol and GABA, respectively). The apparent affinity of the GABA(A) receptor antagonist bicuculline methiodide to inhibit the binding of [3H]SR 95531 did not differ between the two receptor complex variants. Electrophysiological measurements of GABA induced whole-cell Cl- currents showed a ten-fold decrease in the GABA(A) receptor sensitivity of alpha1 (val 121) beta2gamma2 as compared to alpha1(ile 121) beta2gamma2 receptor complexes. Thus, a relatively small change in the primary structure of the alpha1 subunit leads to a decrease selective for GABA(A) receptor sensitivity to agonist ligands, since no changes were observed in a GABA(A) receptor antagonist affinity and benzodiazepine receptor binding.

Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations. No effect or small increases in levels of unsaturated FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2 receptor combinations were observed, and weak effects (130% of control values) were detected using the alpha 5 beta 2 gamma 2 receptor combination. The saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM binding to any combination of receptor complexes. The hydroxylated unsaturated FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to vary at both cellular and regional levels.

Microbiologically verified diagnosis of infectious spondylitis using CT-guided fine needle biopsy.

Using a computed tomography (CT)-guided technique we have been able to obtain fine needle spine biopsies directly from an affected vertebra or disk plate in 14 patients suspected of infectious spondylitis. The bioptic material was cultivated immediately and incubated for 14 days. Cultures from eight patients were positive. No single microbiological agent was predominant though coagulase-negative staphylococci were frequent. In no case were mycobacteria found. Bioptic material from six patients did not give rise to growth of microorganisms. We were able to successfully treat the eight patients with a culture-positive biopsy. We think that biopsies are crucial for establishing a microbiological diagnosis. The whole procedure takes less than one hour; it is performed under local anaesthesia and is thus not very stressful for the patient: The success rate for obtaining a positive spine biopsy was 57%.

Production of [3H]choline-labelled metabolites from endogenously 3H-labelled phosphatidylcholine in mouse pancreatic islets.

The involvement of phosphatidylcholine (PC) hydrolysis in the regulation of insulin secretion was studied in mouse pancreatic islets prelabelled with [3H]choline. Phospholipase C (PLC) and phospholipase D (PLD) activities were demonstrated and also that of an enzyme that removes both fatty acids from PC and thus catalyses the production of [3H]glycerophosphorylcholine (GroPCho). After 2 min of incubation with 20 mM glucose a 35% increase in the content of [3H]GroPCho was observed in prelabelled islets, whereas the amount of [3H]lysoPC, [3H]phosphorylcholine (PCho) and [3H]choline was unaffected. After 30 min of incubation with 20 mM glucose, 0.2 mM tolbutamide, 40 mM KC1, 10 mM succinic acid monomethyl ester (SME) or 10 mM NaF, a 25-50% increase in [3H]GroPCho was observed. In the presence of 100 microM diazoxide or 35 microM RHC 80267 the glucose activation was attenuated. PLC was stimulated slightly by tolbutamide and 100 microM isoprenaline (isoproterenol), whereas SME decreased the amount of [3H]PCho by 10%. [3H]Choline content was increased by 25-40% in the presence of 0.16 microM 12-O-tetradecanoylphorbol 13-acetate (TPA), 10 mM NaF or 100 microM carbachol. This effect of fluoride was potentiated in the presence of 20 mM glucose. It is concluded that metabolism of PC to GroPCho may be involved in the regulation of glucose-stimulated insulin secretion, and that PLD may participate in insulin secretion evoked by TPA, carbachol and fluoride.

Role of glucose metabolism and phosphoinositide hydrolysis in glucose-induced sensitization/desensitization of insulin secretion from mouse pancreatic islets.

The role of glucose metabolism and phosphoinositide hydrolysis in glucose-induced sensitization/desensitization of insulin secretion was studied. A change in glucose concentration from 5.5 to 16.7 mM during 22-24 h of pre-exposure of mouse islets in TCM 199 culture medium (0.26 mM Ca2+) led to sensitization of glucose-induced insulin secretion. This change in islet responsiveness to glucose was not mediated by increases in glucose utilization ([5-3H]glucose conversion to 3H2O) and glucose oxidation ([U-14C]glucose oxidation to 14CO2). Glucose-induced sensitization of insulin secretion was associated with an increase in glucose-induced phosphoinositide hydrolysis, leading to a significant increase in inositol 1-monophosphate formation, but not in inositol 1,4-bisphosphate or in inositol 1,4,5-trisphosphate plus inositol 1,3,4-trisphosphate formation. Diacylglycerol, which may arise from both phosphoinositide hydrolysis and de novo from glucose metabolism, was, on the other hand, not increased during acute exposure to glucose and not changed after pre-exposure to glucose. At 16.7 mM glucose in TCM 199 medium, a change in Ca2+ concentration from 0.26 to 1.26 mM led to a reduction in glucose-induced insulin secretion. This Ca(2+)-dependent desensitization of insulin secretion in the presence of glucose was associated with a decrease in glucose-induced phosphoinositide hydrolysis, but not with a change in glucose metabolism or diacylglycerol accumulation. In conclusion, it is suggested that glucose-induced sensitization/desensitization of insulin secretion may involve changes in phosphoinositide hydrolysis, but may occur independently of concomitant changes in glucose metabolism or diacylglycerol accumulation.