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.

Presence of ATP-pyrophosphohydrolase in mouse pancreatic islets.

The presence of an enzyme that hydrolyzes ATP to AMP and PPi was demonstrated in a 27,000 X g particulate and supernatant fraction of mouse pancreatic islets. The enzyme was stimulated by addition of Ca2+, Zn2+, and Co2+. Addition of calmodulin or trifluoperazine had no effect. In the presence of Ca2+ and Zn2+, the Michaelis constant (Km) for ATP was approximately 0.1 mM and the maximum velocity (Vmax) was close to 90 nmol X min-1 X mg protein-1. After preincubation of the islets for 30 min with 16.7 mM glucose or 5 mM glucose with 1 mM 3-isobutyl-1-methylxanthine (IBMX), a three- to fourfold increase in enzyme activity was seen. Direct addition of IBMX or cAMP to the enzyme assay also had a small stimulatory effect. Preincubation with the insulin secretagogues leucine and alpha-ketoisocaproic acid did not affect the enzyme activity. The possible function of the enzyme in pancreatic islets is discussed in relation to hypotheses given for the function of similar enzyme(s) in other tissues.

Inhibin and activin locally regulate rat ovarian folliculogenesis.

The role of inhibin and activin in the initiation of follicular development, growth, and atresia was examined. Human recombinant inhibin (1 microgram) was unilaterally injected into the ovarian intrabursal space of 25-day-old rats. The contralateral ovary served as a control. Recruited growing follicles (350-500 microns) were observed 24 h after injection. The accumulation of follicles was greater in the inhibin-treated ovaries than in contralateral control ovaries. Moreover, the size distribution of the follicles was similar to the distribution of follicles recruited by systemic exogenous PMSG treatment. The effect of inhibin plus PMSG on follicular development was not different from that of PMSG treatment alone. Injection of human recombinant activin (1 microgram) into the ovarian bursa caused follicular atresia. Activin therapy blocked the follicular development caused by PMSG treatment. The effect of inhibin and activin on follicular development was further characterized by measuring the incorporation of [3H]thymidine into dividing cells. Inhibin enhanced follicular thymidine incorporation, while activin decreased granulosa cell proliferation. Furthermore, receptors for inhibin-A (6.4 x 10(3) receptors/cell) and activin-A (2.3 X 10(4) receptors/cell) were identified on granulosa cells. The evidence suggests that inhibin and activin act in a paracrine manner to regulate follicular development, inhibin as a follicular growth signal and activin as an atretagenic signal.

The pharmacokinetics, tissue localization, and metabolic processing of recombinant human hepatocyte growth factor after intravenous administration in rats.

Hepatocyte growth factor (HGF) is a pluripotent mitogen thought to be involved in liver regeneration. It is synthesized as a single chain promitogen and requires proteolytic processing to a two-chain heterodimeric form for biological activity. The pharmacokinetics and tissue distribution of radioiodinated single chain recombinant human HGF ([125I]rhuHGF) were studied in male Sprague-Dawley rats after an iv bolus dose. Pharmacokinetic parameters were determined from trichloroacetic acid-precipitable radioactivity in serum samples. There was a rapid distribution phase (t1/2 alpha = 3.1 min) and a slower elimination phase (t1/2 beta = 114 min). Tissue distribution was assessed by whole body autoradiography 5, 60, and 1440 min after an iv bolus dose. rhuHGF rapidly distributed to the liver, kidney, adrenal gland, and spleen. The importance of the liver in the rapid clearance and subsequent conversion of single chain pro-rhuHGF to the mitogenically active two-chain form was demonstrated using an isolated rat liver perfusion system. TCA-precipitable radioactivity excreted into the bile (1.0 +/- 0.1%) and released into the venous effluent (38.9 +/- 6.1%) was monitored for 60 min after a portal vein injection. The appearance of radioactivity in both the bile and venous effluent was maximal between 20-35 min. Further characterization of the reduced samples by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that the two-chain form of [125I]rhuHGF was the predominant form after hepatic perfusion. These studies suggest that the liver plays a major role in the rapid clearance and subsequent activation of pro-rhuHGF in vivo.

Pharmacokinetic profile of recombinant human (rh) inhibin A and activin A in the immature rat. II. Tissue distribution of [125I]rh-inhibin A and [125I]rh-activin A in immature female and male rats.

The tissue distribution of recombinant human inhibin A (rh-inhibin A) and rh-activin A was determined in immature female Sprague Dawley-derived rats after iv administration of radiolabeled proteins. [125I]rh-Inhibin A and [125I]rh-activin A diverge in their distribution to tissues of the immature female rat as examined histologically (whole body autoradiography and thin section analysis) and by computing the percent dose and tissue to blood ratios for individual tissues. [125I]rh-inhibin A accumulated in the spleen, adrenal, bone marrow, and ovary after iv injection. Iodinated rh-inhibin A was also found in the anterior and posterior pituitary. [125I]rh-activin A was found in the ovary and pituitary after iv injection. Little specific binding was found in the spleen or adrenal. The bone marrow accumulated some [125I]rh-activin A which was competed by rh-activin A. The primary route of excretion for radioactivity was the kidney, with the label appearing in the bladder by 10 min after iv injection. Not only do rh-inhibin A and rh-activin A have different pharmacokinetics, but fewer tissues accumulate radioactive rh-activin A than rh-inhibin A.

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.

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%.

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.

Increase in glia-derived nerve growth factor following destruction of hippocampal neurons.

It is currently believed that under normal conditions hippocampal neurons synthesize nerve growth factor (NGF) which may provide trophic support for cholinergic neurons projecting from the basal forebrain. The concept that glial cells are mobilized to increase the production of NGF following destruction of hippocampal neurons was examined. Excitotoxin-induced destruction of the dorsal hippocampal neurons resulted in a massive and prolonged increase in NGF-like immunoreactivity (LI). Immunostaining for NGF-LI and the glial marker, glial fibrillary acidic protein (GFAP), revealed that the source of increased NGF-LI production following the lesion were reactive astrocytes. Thus, glial cells assume the role of providing trophic support following loss of target neurons.

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.

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.

Long-term fat-feeding-induced insulin resistance in normal NMRI mice: postreceptor changes of liver, muscle and adipose tissue metabolism resembling those of type 2 diabetes.

Postreceptor insulin resistance was studied in liver, muscle and adipose tissue from NMRI mice of both sexes made diabetic by long-term fat-feeding. Intravenous glucose tolerance tests showed a combination of impaired glucose tolerance and increased plasma insulin concentrations consistent with insulin resistance and reduced peripheral and hepatic uptake of glucose. In the morning, the fat-fed mice were normoinsulinaemic and hyperglycaemic. Liver glucokinase activity and glycogen content were reduced whereas lactate dehydrogenase activity was enhanced. Fatty acid synthase activity was decreased but glucose 6-phosphate dehydrogenase and the rate limiting enzyme in fatty acid synthesis, acetyl CoA carboxylase, were both unaffected. In muscle, the proportion of glycogen synthase in the active I-form was decreased. Total glycogen synthase activity was not affected. In isolated adipocytes, basal and insulin-stimulated glucose oxidation, as well as basal and insulin-stimulated lipogenesis from glucose were all severely inhibited, oxidation more so than lipogenesis. It is concluded that insulin resistance and postreceptor metabolic disorders in liver, muscle and adipose tissue from mice made diabetic by long-term fat-feeding are very similar to those demonstrated in human type 2 diabetics and may be studied in more detail and with more ease in this particular animal model.

Fat-induced changes in mouse pancreatic islet insulin secretion, insulin biosynthesis and glucose metabolism.

Insulin secretion, insulin biosynthesis and islet glucose oxidation were studied in pancreatic islets isolated from fat-fed diabetic mice of both sexes. Insulin secretion from isolated islets was studied after consecutive stimulation with alpha-ketoisocaproic acid + glutamine, glucose, forskolin, and 12-O-tetradecanoylphorbol 13-acetate. Glucose-induced insulin secretion was impaired in islets from fat-fed mice. This was associated with a reduction of approximately 50% in islet glucose oxidation. Islet insulin secretion stimulated by the non-carbohydrate secretagogues tended to be higher in the fat-fed mice, but a statistically significant effect was not observed. Pancreatic insulin content was reduced by 50%, whereas the islet insulin and DNA content was unchanged after fat feeding. Proinsulin mRNA was reduced by 35% in islets from fat-fed mice, and was associated with a reduction of approximately 50% in glucose-stimulated (pro)insulin biosynthesis. It is concluded that the insulin secretory response of islets isolated from fat-fed mice is similar to the secretory pattern known from human type 2, non-insulin-dependent diabetics, and that a defect in islet glucose recognition, resulting in decreased glucose oxidation, may be responsible for the observed insulin secretory and biosynthetic defects seen after glucose stimulation.

Effect of new bonding systems on microleakage.

This study compared Scotchbond 2, Gluma, Tenure, and Light Cured Scotchbond (control) dentin adhesives for reduction of microleakage. None of the new-generation bonding systems was significantly more effective in reducing microleakage than Light Cured Scotchbond. In fact, Gluma was even less effective.

Microleakage with Gluma: effects of unfilled resin polymerization and storage time.

An earlier study showed that the Gluma Bonding System permitted more microleakage than other dentin bonding agents. In that study, the unfilled resin was not polymerized prior to placement of the composite resin, as per manufacturer's instructions. The unfilled resin was cured in the other test groups. To evaluate the effect of unfilled resin polymerization on microleakage, Class V cavity preparations were made in sound extracted teeth. Composite resin restorations were placed using the Gluma Bonding System and a microfilled composite resin. In some samples, the unfilled resin was cured prior to placement of the composite. In others, the unfilled resin and composite were polymerized simultaneously. The samples were stored for either 24 hours or 30 days, then thermocycled. Microleakage was evaluated with a silver nitrate staining method. Specimens in which the unfilled resin had not been cured separately and which had been stored for 24 hours had the most leakage. Significantly less microleakage occurred when the unfilled resin was polymerized separately and/or when storage time was 30 days. To reduce microleakage with the Gluma Bonding System, the authors recommend polymerization of the unfilled resin before placement of the composite.

Fluoride release from fast-setting glass ionomer restorative materials.

New fast-setting glass ionomer restorative materials have been developed. This study compared fluoride release from two of these materials with that of a slower-setting material. Although each material released fluoride ions continuously, the slower-setting material released the highest concentrations.

Effects of the XR bonding system on microleakage.

Bonding of composite resins to dentin is generally less effective and less predictable than bonding to enamel. Several new dentin bonding agents have been developed to improve adhesion. One of these products, the XR Bonding System, includes a glass ionomer liner and a resin dentin adhesive. Our study found that the resin dentin adhesive (primer and bonding agent) did not reduce microleakage effectively. However, when used in combination with the glass ionomer liner, the resin bonding system allowed very minimal microleakage.

[Osteoporotic fractures of the spine in elderly women. Risk factors, inducing factors and course]. / Osteoporotisk fraktur i columna hos aeldre kvinder. Risikofaktorer, udløsende faktorer og forløb.

Forty-seven women with osteoporotic fractures of the spine were examined consecutively. The age range was 64-91 years with a median of 77 years. Risk factors for osteoporosis such as induced menopause or gastric resection were not present. Four patients had had rheumatoid arthritis. 19% had been treated with glucocorticoid. Only one patient had received long-term oestrogen treatment. The patients had been physically very active at a younger age and 91% had been occupationally employed. The symptoms frequently commenced with a fall or strain by lifting at home. The average period of hospitalization was 22 days. Thirty-four patients were followed-up after 6-12 months. All of them experienced pain and 74% still took analgesics. Fifteen out of the 19 patients who had been fitted with a supportive corset still employed this.