H. A. Bird

The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome)

The Lack of Clinical Distinction Between the Hypermobility Type of Ehlers–Danlos Syndrome and the Joint Hypermobility Syndrome (a.k.a. Hypermobility Syndrome) Brad T. Tinkle,* Howard A. Bird, Rodney Grahame, Mark Lavallee, Howard P. Levy, and David Sillence Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio University of Leeds, West Yorkshire, United Kingdom University College Hospital, London, United Kingdom Memorial Sports Medicine Institute, South Bend, Indiana Johns Hopkins University, Baltimore, Maryland Connective Tissue Dysplasia Management Service, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia

CAPTOPRIL: A NEW TREATMENT FOR RHEUMATOID ARTHRITIS?

Captopril, an inhibitor of angiotensin converting enzyme, is prescribed for hypertension. Its molecular structure shares features with D-penicillamine, in that both agents contain a thiol group. In addition, captopril has immunosuppressant activity. Captopril was therefore considered a potential slow-acting drug for treating rheumatoid arthritis. In an open study 15 patients with active arthritis were treated with captopril and followed for 48 weeks. Two-thirds of the patients reported improved arthritis symptoms, and significant changes were seen in several clinical and biochemical measurements, notably Ritchie articular index, clinical score, plasma viscosity, and C-reactive protein. Side-effects were generally mild and included transient taste loss, rashes, and hypotension. Only 2 patients withdrew as a result of drug intolerance.

Measurement of the cross linking compound, pyridinoline, in urine as an index of collagen degradation in joint disease.

An enzyme linked immunoassay (ELISA) for the collagen cross link, pyridinoline, has been developed using affinity purified antibodies, with a sensitivity down to about 0.1 ng of cross link. Measurements of urinary pyridinoline were made in patients with rheumatoid arthritis (RA), osteoarthritis (OA), and a control group showing no signs of joint disease. Expressed relative to creatinine values, pyridinoline was significantly increased in both RA and OA groups compared with controls: these differences were much larger than could be attributed to any age related effects or to changes in urinary creatinine concentrations. These findings were confirmed by analysis of a series of 24 h urine collections which showed that the total pyridinoline excretions were significantly higher in both RA and OA groups than in the controls. As pyridinoline is much more prevalent in cartilage than in bone collagen, measurement of this compound in urine may provide an index for monitoring the increased joint destruction that occurs in arthritic disease.

The Effect of Bone Morphogenetic Protein-2, Bone Morphogenetic Protein-7, Parathyroid Hormone, and Platelet-Derived Growth Factor on the Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells Derived From Osteoporotic Bone

Introduction: It has been previously shown that in patients with osteoporosis, mesenchymal stem cell (MSC) growth rate and osteogenic potential is decreased contributing to inferior fracture consolidation. The aim of this study was to investigate the effect of bone morphogenetic protein-2 (BMP-2), BMP-7, parathyroid hormone (PTH), and platelet-derived growth factor (PDGF) on proliferation and osteogenic differentiation of MSCs derived from patients with osteoporosis. Materials and Methods: Trabecular bone was obtained from 10 patients (four males, mean age 76 years) with lower extremity osteoporotic fractures. MSCs were isolated by enzymatic digestion. Functional assays of proliferation and osteogenic differentiation were performed under the influence of a wide range of concentrations of BMP-2, BMP-7, PTH, and PDGF-BB. Proliferation was assessed using CFU-F and XTT assays. Osteogenic differentiation was assessed by alkaline phosphatase activity and total calcium production. Results: MSC proliferation was found to be stimulated by supplementation with BMP-7 and PDGF-BB, whereas BMP-2 and PTH had little effect. The largest increase in proliferation rate was observed after administration 100 ng/mL of BMP-7. All four molecules induced alkaline phosphatase activity and calcium production in growing osteoblasts with a dose-dependent effect noted. BMP-2 and BMP-7 at their highest studied concentration (100 ng/mL) produced a threefold increase in the osteogenic potential of MSCs. Conclusion: BMP-7, BMP-2, PTH, and PDGF-BB were observed to have a positive effect on osteogenic differentiation of MSCs. BMP-7 and PDGF-BB (in high doses) could be considered most potentially advantageous because they enhance both proliferation and osteogenic differentiation of MSCs derived from elderly osteoporotic bone.

Comparison of sleep in osteoarthritic patients and age and sex matched healthy controls.

A sleep laboratory comparison of the sleep of 14 osteoarthritic patients with that of 16 age and sex matched healthy controls was undertaken. After three nights of adaptation continuous recordings of electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activity were obtained for the next two nights. A comparison of EEG sleep variables during this baseline period showed that osteoarthritic patients had a significantly greater percentage of stage 1 and significantly smaller percentage of stage 2 sleep than control subjects. These findings indicate sleep disturbance in osteoarthritic patients. The limited degree of disturbance observed in these patients may be due to the fact that they were allowed to continue with their normal anti-inflammatory and analgesic medication for the course of the study.

Outcomes for patients with RA: a rheumatology nurse practitioner clinic compared to standard outpatient care.

OBJECTIVES The study aimed to extend our previous work by comparing the outcome of patients with rheumatoid arthritis (RA) attending a rheumatology nurse practitioner (RNP) clinic with those of patients attending the more traditional junior hospital doctors clinic (JHD). METHOD A randomised controlled trial of 80 people with RA were allocated to either an RNP or JHD clinic and seen six times in 12 months. The primary outcome measure was the DAS28. Secondary measures included stiffness, fatigue, physical function, psychological status, knowledge and satisfaction. RESULTS Number of patients: RNP 39 (8 males); JHD 41 (9 males). Age of patients: RNP 36-76 years (median 57); JHD 35-74 years (median 57). Median disease duration: RNP 12 years (range 2-40); JHD 17 years (range 1.5-41). Years of full time education: RNP 8-17 years (median 10); JHD 9-20 years (median 10). Week 48 DAS scores compared to baseline: RNP 19 unchanged, 6 worse and 11 better; JHD 22 unchanged, 7 worse, 6 better. Length of morning stiffness increased significantly at week 24 (p = 0.05) in the JHD cohort but improved to become non-significant at week 48 (p = 0.09). By week 48 fatigue had improved in the RNP cohort (p = 0.038) and deteriorated in JHD patients (p = 0.008). The AIMS showed decreases in pain in the RNP cohort (p = 0.044) and worsening physical function in JHD patients (p = 0.038). Patient satisfaction in the RNP cohort increased significantly (overall satisfaction p = 0.000). The JHD cohort showed a decrease in satisfaction with access and continuity (p = 0.027). CONCLUSIONS The findings from this research confirm that care from the RNP is both effective and safe. Furthermore, a specialist RNP can bring additional benefits in the form of greater symptom control and enhanced patient self-care.

A comparison of the sensitivity of diagnostic criteria for polymyalgia rheumatica

Objective: To compare the performance of the several different diagnostic criteria sets currently in use for polymyalgia rheumatica (PMR). Methods: 213 patients attending eight rheumatological centres in eight different European countries were studied. All had recently been referred and were considered by the senior investigator at each centre, selected because of their experience in treatment of PMR, to have this condition. By use of a standard international proforma, the requisite diagnostic points in each criteria set were sought. Sensitivity for each criterion from each set was then calculated, as well as the sensitivity of each criteria set as a whole. Results: Of four criteria sets compared, the Bird (1979) criteria performed best with a sensitivity of 99.5%, and the Hunder (1982) criteria second best, with sensitivity of 93.3%. These both performed significantly better than the two other criteria sets, though each of these was admittedly developed for rather specialised reasons. Conclusions: Although this study compares homogeneity, we suggest the Bird 1979 or Hunder 1982 criteria should be used whenever possible. Studies that have used alternative criteria may have less sensitivity in diagnosis.

Survey of satisfaction with care in a rheumatology outpatient clinic.

Consumer satisfaction is increasingly recognised by hospital administrators and health care providers as an important aspect of health care. A study was undertaken to investigate the satisfaction with care among patients with rheumatoid arthritis (RA) attending a rheumatology outpatient clinic at Leeds General Infirmary. The Leeds satisfaction questionnaire was developed and rigorously tested for reliability (Cronbachs alpha) and stability (test/retest). The Leeds satisfaction questionnaire was then completed by 70 patients with RA who had attended the Leeds General Infirmary on at least three previous occasions. The results showed that patients were, in general, satisfied with the care they received. The highest satisfaction scores were obtained on the scale for technical quality and competence of health professionals. The least satisfaction was accredited to the difficulty of unscheduled access to the clinic and the lack of continuity with the providers of care. The time spent in the waiting area before consultation was highlighted as the one aspect which caused the greatest dissatisfaction.

A comparison of clinical assessments of disease activity in rheumatoid arthritis.

Six clinical assessments of disease activity, including a new summated change scale (SCS), have been compared in a group of 30 patients with rheumatoid arthritis seen on 8 separate occasions during their first 6 months of therapy with either D-penicillamine or hydroxychloroquine. Articular index and grip strength correlate best with erythrocyte sedimentation rate and C-reactive protein, pain score and early morning stiffness less well, and summated change score and joint circumference least well. Articular index and grip strength also correlated well with the other clinical parameters and are therefore judged to be the best clinical indices of change in treatment with these drugs.

A double-blind controlled trial of etretinate (Tigason) and ibuprofen in psoriatic arthritis.

Etretinate (Tigason) and ibuprofen have been compared in a double-blind controlled trial in psoriatic arthritis to see if we could confirm a specific action for this vitamin A derivative suggested from earlier uncontrolled studies. Eleven out of 20 patients completed 24 weeks of therapy with etretinate (up to 0.5 mg/kg/day) whereas only 1/20 patients completed 24 weeks of therapy with ibuprofen alone. Etretinate improved skin lesions, and this may have encouraged patients to persist with it. Improvement of statistical significance was seen for articular index in both groups. In addition significant improvement in ESR, haemoglobin, C-reactive protein, and histidine occurred in the etretinate group. The main side effects of etretinate (which may preclude its use at a higher dose in this condition) included cracked and dried lips and sore mouth.