The effect of progressive resistance training in rheumatoid arthritis. Increased strength without changes in energy balance or body composition

Objective. To demonstrate the feasibility of high-intensity progressive resistance training in rheumatoid arthritis (RA) patients compared with healthy control subjects. Methods. Eight subjects with RA, 8 healthy young subjects, and 8 healthy elderly subjects underwent 12 weeks of high-intensity progressive resistance training, while 6 elderly subjects performed warm-up exercises only. Fitness, body composition, energy expenditure, function, disease activity, pain, and fatigue were measured at baseline and followup. Results. All 3 training groups demonstrated similar improvements in strength compared with the change among control subjects (RA group 57% [P < 0.0005], young exercise group 44% [P < 0.01], elderly exercise group 36% [P < 0.05]). Subjects with RA had no change in the number of painful or swollen joints but had significant reductions in self-reported pain score (21% [P < 0.05]) and fatigue score (38% [P = 0.06]), improved 50-foot walking times (mean ± SD 10.4 ± 2.2 seconds versus 8.3 ± 1.5 seconds [P < 0.005]), and improved balance and gait scores (48.9 ± 3.8 versus 50.4 ± 2.0 [P = 0.07]). Conclusion. High-intensity strength training is feasible and safe in selected patients with well-controlled RA and leads to significant improvements in strength, pain, and fatigue without exacerbating disease activity or joint pain.     

Comparative screening for thyroid disorders in old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake

OBJECTIVE The bisphosphonates have proven efficacy in the management of post-menopausal osteoporosis. However, the benefits of prolonged (<2 years) administration and the effects of discontinuation of bisphosphonate treatment are not clear. DESIGN We have previously reported a 2-year, randomized, double-blind, placebo-controlled trial of pamidronate therapy (150mg/day) in women with established post-menopausal osteoporosis. We now report the bone mineral density (BMD) changes in those women who continued for a third year of active treatment and were then observed off therapy for a further 12 months. PATIENTS Twenty-two women (mean age 66 years) continued on pamidronate in year 3, and in 16 of these the effects of subsequent discontinuation of therapy for 12 months were studied. MEASUREMENTS BMD was measured in the total body, lumbar spine and proximal femur using a Lunar DPX-L dual-energy, X-ray absorptiometer. RESULTS The third year of therapy with pamidronate was associated with a significant further gain in BMD only at the lumbar spine (2.1±0.8%, P=0.003), resulting in a total gain of 9.5±1.0% at that site over 3 years of treatment. In the total body, BMD tended to decline (?0.6±0.3%) in year 3. One year after discontinuation of pamidronate, there were significant losses of BMD in the total body (?1.9±0.3%, P<0.0001) and femoral trochanter (?2.7±0.9%, P=0.01), and non-significant changes at the lumbar spine (?0.9±0.8%), femoral neck (?0.5±1.6%), and Ward's triangle (?2.9±3.7%). By the end of one year off therapy, BMD was greater than baseline only in the lumbar spine (71±1.1%, P<0.0001) and femoral trochanter (4.5±1.88%, P<0.03). In the total body, BMD was 0.3±0.7% below the values at the trial’s inception (P=0.7). CONCLUSIONS These data demonstrate that the rate of bone gain associated with bisphosphonate use slows over time, and that significant bone loss follows withdrawal of these agents. These findings have important implications for the duration of use of these novel drugs in the therapy of osteoporosis and suggest a need for close observation following their discontinuation.     

Associations with subregional BMD-measurements in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have bone loss to various degrees at different skeletal sites. The subregional bone mineral density (BMD) of the hand and the correlation of BMD to other regional bone losses, parameters of inflammation or bone resorption was evaluated in 421 patients with RA and controls. RA patients had significantly (P < 0.01) lower BMD values in the carpus (0.405 ± 0.004 g/cm²), metacarpal joint II (0.318 ± 0.036 g/cm²) and metacarpal joint III (0.326 ± 0.022 g/cm²) compared to controls. There was no difference in bone density at the lumbar spine or hip. Significant (P < 0.001) correlations were found between BMD total of the hand, its subregions, the forearm and hip. Parameters of inflammation correlated significantly (P < 0.001) with pyridinolines (r = 0.378), desoxypyridinolines (r = 0.183), forearm (r = −10, P < 0.05), MCP II (r = −0.190, P < 0.001), MCP III (r = 0.204, P < 0.001) and carpus (r = 0.191, P < 0.001).     

Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia

Serum immunoreactive erythropoietin (EP) levels were measured in 116 patients with rheumatoid arthritis (RA) and 20 control patients with iron deficiency anemia. Serum EP levels were significantly higher in the 46 anemic RA patients than in the 70 nonanemic RA patients (mean ± 1 SD 31.0 ± 19.8 mU/ml versus 16.8 ± 12.4 mU/ml; P < 0.0001). Furthermore, although a significant inverse correlation between the serum EP level and the hemoglobin value was present in the anemic RA patients (r = −0.57, P < 0.0001), the regression coefficient describing the relationship between serum EP and hemoglobin was significantly lower for the anemic RA patients than for patients with iron deficiency anemia (F = 6.01, P < 0.025).     

Abnormal homocysteine metabolism in rheumatoid arthritis

Objective. To assess total homocysteine (tHcy) metabolism in patients with rheumatoid arthritis (RA). Methods. Assessments were performed to determine the fasting levels of tHcy and the increase in tHcy in response to methionine (Met) challenge in blood samples from 28 patients with RA and 20 healthy age-matched control subjects. Results. Fasting levels of tHcy were 33% higher in the RA patients than in the control subjects (mean ± SD 11.7 ± 1.5 nmoles/ml versus 8.8 ± 1.1 nmoles/ml; P < 0.01). Four hours after Met challenge, the increase in plasma tHcy levels (ΔtHcy) was higher in the RA patients (20.9 ± 10.4 nmoles/ml) than in the control subjects (15.5 ± 1.6 nmoles/ml) (P < 0.02). In a subgroup analysis, the ΔtHcy in patients taking methotrexate (12.9 ± 2.2 nmoles/ml) did not differ from that in the control group, while the ΔtHcy in patients not taking methotrexate (25.3 ± 1.7 nmoles/ml) was significantly higher (P < 0.0001). Conclusion. Elevated tHcy levels occur commonly in patients with RA, and may explain some of the increased cardiovascular mortality seen in such patients. Studies of the prevalence and mechanism of hyperhomocysteinemia in RA are warranted.     

Rheumatoid arthritis in greek and british patients. a comparative clinical,radiologic, and serologic study

Objective. To compare the clinical, radiologic, and serologic expression of rheumatoid arthritis (RA) in 2 different populations. Methods. Standard protocols and assessment criteria were used in this study of 108 Greek and 107 British patients with RA. Results. British patients had more severe articular involvement than did Greeks, as judged by the duration of morning stiffness (P < 0.005), grip strength (P < 0.0001), and the numbers of swollen (P < 0.001) and tender (P < 0.0001) joints. The British RA patients also had more severe joint damage on radiologic examination, as evidenced by Steinbrocker stage III (P < 0.005) and IV (P < 0.025) disease and had more extraarticular manifestations (P < 0.0001), including rheumatoid nodules (P < 0.0001) and Raynaud's phenomenon (P < 0.05). Greek RA patients, however, more frequently presented with sicca manifestations (P < 0.001) and serum antibodies to Ro/SS-A (P < 0.025). Furthermore, Ro/SS-A antibodies were associated with a high incidence of side effects to D-penicillamine only in the Greeks. Conclusion. Genetic and environmental factors may be responsible for these striking differences in disease expression between these 2 European populations with RA.     

Relationship between bone mineral density and duration of rheumatoid arthritis

BackgroundLonger disease duration is believed to be associated with more pronounced bone loss in rheumatoid arthritis (RA). This study was designed to assess bone mineral density (BMD) status in RA compared with age-matched control in relation to disease duration.MethodsThis study included 177 RA and 283 age-matched non-RA controls. BMD at the femoral neck and lumbar spine was assessed by Dual Energy X-ray Absorptiometry Osteoporosis was diagnosed according to WHO criteria. We divided patients with RA into groups based on disease duration of <2, 2–5, 5–10, and >10 years and compared them with controls. The relationship between disease duration and BMD was investigated by chi square and Spearman test.ResultsMean age of patients and control subjects was 51.2 ± 12.5 and 52.2 ± 6.7 years, respectively and mean disease duration was 86.5 ± 73.3 months. Osteoporosis at the femoral neck and lumbar spine in patients with RA was significantly higher than in controls. Femoral neck BMD in RA was negatively correlated with disease duration and 4.5% variations of femoral neck BMD was explained by disease duration (r² = 0.045, P = 0.005). Odds Ratio (OR) for osteoporosis in RA patients as compared to controls was increased by prolongation of disease duration from 2.38 (0.38–14.7) in patients with disease duration <2 years to 12.56 (2.24–70.2) in patients with disease duration >10 years. For patients treated with methotrexate compared to those who had never received methotrexate the odds ratio for femoral neck osteoporosis reduced by 64% (OR = 0.36, 95% CI, 0.15–0.91).ConclusionThere is a significant negative relationship between femoral neck BMD and disease duration in RA. The value of OR increases proportionately with lengthening of disease duration which can be reduced significantly by methotrexate therapy.     

Bone mineral density in children with cirrhosis

Background Despite the clinical importance of osteoporosis in individuals with cirrhosis, little is known about it, especially in children. We evaluated the bone mineral density (BMD) and bone mineral content (BMC) of children with cirrhosis. Methods Forty children with cirrhosis (mean age, 10.4 ± 3.9 years) were involved. BMD and BMC were measured by dual energy X-ray absorptiometry at lumbar vertebrae 1–4, and the results were compared with those of 62 healthy age- and sex-matched children. Results The mean lumbar spine BMD of patients with cirrhosis was 0.482 ± 0.107 g/cm² and that of the controls was 0.687 ± 0.172 g/cm² (P < 0.0001). The mean lumbar spine BMC of patients with cirrhosis was 20.008 ± 8.409 g and that of controls was 32.859 ± 14.665 g (P < 0.0001). After the confounding variables (weight, height, and pubertal stage) were controlled for, the difference in BMD and BMC values between patients with cirrhosis and healthy controls was significant (0.535 ± 0.061 g/cm² vs 0.653 ± 0.048 g/cm², and 24.515 ± 5.052 g vs 29.952 ± 3.971 g, respectively). Conclusions Because of the significant difference in BMD and BMC values between our patients with cirrhosis and healthy controls, patients with cirrhosis should be evaluated for osteopenia.     

A transforming growth factor-β1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura

 Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-β1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) <50×10⁹/l, (2) 50–150×10⁹/l and (3) >150×10⁹/l. We found significantly elevated plasma levels of the Th3 cytokine TGF-β1 in patients with pltc >150×10⁹/l (23.5±2.8 ng/ml), compared with patients with pltc <50×10⁹/l (2.3±0.6 ng/ml;P<0.0001), patients with pltc 50–150×10⁹/l (7.2±1.7 ng/ml;P<0.0001) and healthy volunteers (9.8±1.3 ng/ml;P<0.01). The serum levels of the Th1 cytokines interleukin (IL)-2 and interferon (IFN)-γ were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc <50×10⁹/l had significantly lower levels (0.6±0.1 pg/ml) than both patients with pltc 50–150×10⁹/l (1.8±0.1 pg/ml;P<0.005) and healthy volunteers (1.4±0.1 pg/ml;P<0.005). Furthermore, patients with pltc <50×10⁹/l and splenectomised patients had significantly higher levels of CD4+CD25+ activated T cells [26.2±14.8% (P<0.05) and 26.7±11.9% (P<0.005), respectively] than healthy controls (16.5±4.0%). Also, the number of natural killer (NK) cells among patients with pltc >150×10⁹/l were significantly elevated (26.6±16.0%;P<0.05) compared with controls (17.4±7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-β1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-β1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease. Received: 29 September 1999 / Accepted: 25 January 2000     

Discrepancy between visual estimation and computer-assisted measurement of lesion severity before and after coronary angioplasty

One hundred fourteen coronary stenoses were quantified before and after percutaneous transluminal coronary angioplasty (PTCA) using a semi-automated digital system. The values obtained were considered as standard for comparison with visual estimation by the PTCA operator as well as by independent consensus-reading. The measured percent stenosis was 62.7 ± 13.7% before and 27.7 ± 12.4% after angioplasty. Before PTCA, the operator consistently overestimated stenosis severity (87.8 ± 8.5%, P < 0.0001) and consensus-reading reduced but did not eliminate this overestimation (78.0 ± 12.3%, P < 0.05). The error in visual estimation was inversely correlated with the measured degree of stenosis: coefficients were –0.79 (P < 0.0001) and –0.51 (P < 0.0001) for operator and consensus-readers, respectively. After PTCA, the operator underestimated the residual stenosis (21.2 ± 9.9%, P < 0.0001) but there was no systematic bias by consensusreading (29.4 ± 12.0%, NS). Again the error in visual estimation was inversely correlated with the measured degree of residual stenosis : coefficients were –0.76 (P < 0.0001) and –0.58 (P < 0.0001) for operator and consensus-reading, respectively. In conclusion, the operator overestimates lesion severity before and underestimates moderate residual stenoses after PTCA, a problem only partially corrected by independent consensus-readers.     

HLA-DRB1 allele distribution and its relation to rheumatoid arthritis in eastern Black Sea Turkish population

Rheumatoid arthritis (RA [MIM 180300]) is a complex, polygenic inflammatory autoimmune disease, resulting from interactions between genetic and environmental factors. Some of the RA-associated HLA-DRB1 alleles have shared epitope, but their distribution varies among different racial/ethnic groups. This study was aimed at investigating the distribution of HLA-DRB1 alleles in patients with RA in eastern Black Sea region of Turkey. DNA samples of 320 patients with RA and 360 healthy controls were studied for the determination of HLA-DRB1 allele distribution using PCR–SSP method. The allele frequencies of HLA-DRB1*01, *04, and *09 were higher in patients with RA compared with the controls (P < 0.005, P < 0.0001, and P < 0.01, respectively). On the other hand, in patients with RA, HLA-DRB1*13 allele was lower than the controls (P < 0.001). Of the HLA-DRB1*04 subgroups, *0401 (40.83% vs. 18.75%, P < 0.001) was the most frequent allele in patients with RA, while DRB1*0402 (30.00% vs. 12.50%, P < 0.005) allele in the controls. HLA-DRB1 allele frequencies in the patients with RA and the controls showed Hardy–Weinberg rule compliance. Results of this study indicate that HLA-DRB1*01, *04, and *09 alleles were associated with RA, and HLA-DRB1*13 was protective allele against RA. Among the subgroups of HLA-DRB1*04, *0401 was detected to be RA associated, while *0402 was being protective. These results have some differences compared with previous reports originating from other regions of Turkey.     

Diastolic heart function in RA patients

The results of some epidemiological studies point to the presence of an increased risk of cardiovascular disease (CVD), particularly atherosclerosis and congestive heart failure (CHF) in rheumatoid arthritis (RA). At least 50% of abnormalities remained asymptomatic. Pathological conditions contributing to myocardial dysfunction such as high serum levels of IL-6, C-reactive protein (CRP) and TNF alpha are present both in RA and CHF patients. The most common pathological mechanism leading to the development of heart failure is left ventricular (LV) diastolic dysfunction, which remains clinically asymptomatic for a long time. The aim of this study was to assess the systolic and diastolic functions of the LV in RA patients without clinically evident cardiovascular disease, using pulsed Doppler echocardiography. Our purpose was also to estimate whether there is a correlation between the duration and severity of RA and the degree of LV diastolic dysfunction. A comparison of the average values of echocardiographic measurements was made between the RA group and control group, which constituted healthy volunteers. Left ventricular mass index in RA group was significantly greater than in the control group (105.2 ± 32.6 vs. 87.9 ± 16.8; p < 0.05) so were the interventricular septum end-diastolic thickness (1.01 ± 0.33 vs. 0.86 ± 0.12; p < 0.05), the LV posterior wall end-diastolic thickness (0.94 ± 0.08 vs. 0.83 ± 0.11; p < 0.0001) and the aortic root diameter (3.18 ± 0.31 vs. 3.10 ± 0.63, p < 0.001). The ejection fraction in RA group was significantly lower than in the control group (64.4 ± 1.3 vs. 66.3 ± 1.3; p < 0.0001). The assessment of diastolic function parameters revealed significantly longer isovolumetrc relaxation time (IVRT) and shorter deceleration time (DT) in RA patients compared to the control group. Patients in stage II or III revealed significantly lower LV mass index (99 ± 17 vs. 131 ± 42; p < 0.05) and the interventricular septum end-diastolic thickness (0.94 ± 0.10 vs. 1.28 ± 0.5; p < 0.05) than those in stage IV. Mean aortic diameter was significantly greater in individuals in stages III and IV (3.73 ± 0.28) than in the stage II of the disease (2.77 ± 0.21), p < 0.05. No differences in echocardiographic parameters’ values were observed between seropositive, seronegative, nodule-present and nodule-absent persons. Echocardiographic examination revealed valvular heart disease in 24 (80%) RA and 6 (20%) control patients (p < 0.0001).     

The effect of instrumental dead space on measurement of breathing pattern and pulmonary mechanics in the newborn

The effect of the instrumental dead space on breathing pattern and the values of pulmonary mechanics was evaluated because of concern about the relatively large dead space of 26 mL in a commercially available system. Sixty-three healthy newborn infants were studied with a system as commercially supplied, and with the dead space eliminated using a 2 L/min biased flow. This led to a significant reduction in mean (± SD) values of respiratory rate from 56.8 (±11.7) to 48.2 (±11.7) breath/min (P < 0.0001), tidal volume from 5.2 (±1.3) to 4.9 (±0.9) mL/kg (P < 0.05), minute volume from 284 (±68) to 220 (±63) mL/min/kg (P < 0.0001), and work of breathing from 13.7 (±6.6) to 11.8 (±7.6) g · cm/kg (P < 0.02). There was a significant increase in dynamic lung compliance from 5.2 (±1.5) to 5.6 (±1.2) mL/cm H₂O (P < 0.01) but no difference for total pulmonary resistance 39.6 (±22.8) and 38.8 (±22.2) cm H₂O/L/sec. This shows that the instrumental dead space prevents measurement of the basal breathing patterns and alters the values of pulmonary mechanics. It is, therefore, important to use equipment with low dead space or make efforts to remove it by using a biased flow system such as we describe when measuring breathing patterns and pulmonary mechanics in the newborn. Pediatr Pulmonol. 1993; 16:316–322. © 1993 Wiley-Liss, Inc.     

Low back pain and other musculoskeletal pain comorbidities in individuals with symptomatic osteoarthritis of the knee: Data from the osteoarthritis initiative

Objective

To examine the association of concurrent low back pain (LBP), and other musculoskeletal pain comorbidity, with knee pain severity in symptomatic knee osteoarthritis (OA).

Methods

Individuals from the Progression Cohort of the Osteoarthritis Initiative (n = 1,389, ages 45–79 years) with symptomatic tibiofemoral knee OA were studied. Participants identified pain in the low back, neck, shoulder, elbow, wrist, hand, hip, knee, ankle, or foot. The primary outcome was the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) applied to the more symptomatic knee. We examined WOMAC pain score in persons with and without LBP, before and after adjusting for other musculoskeletal symptoms.

Results

Of the participants, 57.4% reported LBP. The mean ± SD WOMAC pain score (possible range 0–20) was 6.5 ± 4.1 in participants with and 5.2 ± 3.4 in participants without LBP (P < 0.0001). In multivariate analyses, LBP was significantly associated with increased WOMAC knee pain score (β [SE] = 1.00 [0.21], P < 0.0001). However, pain in all other individual musculoskeletal locations demonstrated similar associations with knee pain score. In models including all pain locations simultaneously, only LBP (β [SE] = 0.65 [0.21], P = 0.002), ipsilateral elbow pain (β [SE] = 0.98 [0.40], P = 0.02), and ipsilateral foot pain (β [SE] = 1.03 [0.45], P = 0.02) were significantly associated with knee pain score. Having >1 pain location was associated with greater WOMAC knee pain; this relationship was strongest for individuals having 4 (β [SE] = 1.83 [0.42], P < 0.0001) or ≥5 pain locations (β [SE] = 1.86 [0.36], P < 0.0001).

Conclusion

LBP, foot pain, and elbow pain are significantly associated with WOMAC knee pain score, as are a higher total number of pain locations. This may have implications for clinical trial planning.     

The significance of platelet activation in rheumatoid arthritis

We evaluated the significance of platelet activation in patients with rheumatoid arthritis (RA). The expression of CD62P and CD63 by platelets was determined using flow cytometry in 18 active RA patients, 10 remission RA and 15 normal controls. Meanwhile, the erythrocyte sedimentation rate (ESR) and C-reactive protein was also determined in all groups. The expression of CD62P in active RA patients (11.88 ± 2.47%) was significantly higher than that in remission RA group (2.85 ± 1.60%; P < 0.01) and control group (2.78 ± 1.04%; P < 0.01). The expression of CD63 in active RA patients (9.90 ± 3.02%) was significantly higher than that in remission RA group (4.11 ± 2.00%; P < 0.01) and control group (4.13 ± 1.85%; P < 0.01). The level of CRP (54.33 ± 23.35 mg/l) and ESR (86.06 ± 33.67 mm/h) in active RA patients was higher than that in remission RA group (2.55 ± 1.01 mg/l, 14.70 ± 4.57 mm/h; P < 0.01 for both) and normal control group (3.21 ± 2.18 mg/l, 12.25 ± 5.05 mm/h; P < 0.01 for both). There was a positive correlation between CD62P and ESR (r = 0.5224, P < 0.01) and also a positive correlation between CD62P and CRP (r = 0.7048, P < 0.01) as well as between CD63 and ESR (r = 0.4476, P < 0.05) but no correlation between CD63 and CRP. Platelet activation may be a sign of RA exacerbation.     

A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes

To evaluate the effect of recombinant human erythropoietin (rHuEpo) on the haemoglobin level and transfusion requirement in low-risk myelodysplastic syndromes (MDS), 87 patients were enrolled in a randomized double-blind placebo-controlled study. 44 patients were assigned to epoetin α (150 U/kg/d s.c. for 8 weeks) and 43 to placebo arms. MDS types were homogenous in both groups: refractory anaemia (RA) 47.7–48.8%, refractory anaemia with ringed sideroblasts (RAS) 20.5–25.6%, refractory anaemia with excess of blasts (RAEB) (blasts < 10%) 31.8–25.6%. 14/38 evaluable patients responded to epoetin α versus 4/37 to placebo (P = 0.007). 50% of RA responded to epoetin α versus 5.9% to placebo (P = 0.0072), RAS 37.5% v 18.2% (P = 0.6) and RAEB 16.7% v 11.1% (P = 1.00). 60% of non-pretransfused patients responded to epoetin α (Hb 8.35 ± 0.73 to 10.07 ± 1.87 g/dl), whereas a slight decrease was observed in the placebo group (8.4 ± 0.66 to 8.19 ± 0.92 g/dl) (P = 0.0004). Percentage of transfused patients was similar in both arms. Basal erythropoietin (Epo) serum levels > 200 mU/l predicted for a non-response. At week 4 sTfR levels were increased > 50% in responders (P = 0.013), whereas an increase < 18% predicted for non-response (P = 0.006). Leucocyte and platelet counts were not influenced by epoetin α treatment. Adverse events occurred in 31.8% of the rHuEpo-treated versus 42.9% of the placebo-treated patients (P = 0.2), and seven patients did not complete the course. In conclusion, rHuEpo was effective in the treatment of low-risk MDS. RA subtype, no transfusions prior to rHuEpo therapy, and low basal Epo levels were associated with higher probability of response. Soluble transferrin receptor level at the fourth week was an early predictor of response.     

Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial

Aims/hypothesis: The management of charcot neuroarthropathy, a severe disabling condition in diabetic patients with peripheral neuropathy, is currently inadequate with no specific pharmacological treatment available. We undertook a double-blind randomised controlled trial to study the effect of pamidronate, a bisphosphonate, in the management of acute diabetic Charcot neuroarthropathy. Methods: Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in England were randomised in a double-blind placebo-controlled trial. Patients received a single infusion of 90 mg of pamidronate or placebo (saline). Foot temperatures, symptoms and markers of bone turnover (bone specific alkaline phosphatase and deoxypyridinoline crosslinks) were measured over the 12 months, in 10 visits. All patients also had standard treatment of the Charcot foot. Results: Mean age of the study group (59 % Type II (non-insulin-dependent) diabetes mellitus) was 56.3 ± 10.2 years. The mean temperature difference between active and control groups was 3.6 ± 1.7 °C and 3.3 ± 1.4 °C, respectively. There was a fall in temperature of the affected foot in both groups after 2 weeks with a further reduction in temperature in the active group at 4 weeks (active and placebo vs baseline; p = 0.001; p = 0.01, respectively), but no difference was seen between groups. An improvement in symptoms was seen in the active group compared with the placebo group (p < 0.001). Reduction in bone turnover (means ± SEM) was greater in the active than in the control group. Urinary deoxypyridinoline in the pamidronate treated group fell to 4.4 ± 0.4 nmol/mmol creatinine at 4 weeks compared with 7.1 ± 1.0 in the placebo group (p = 0.01) and bone-specific alkaline phosphatase fell to 14.1 ± 1.2 u/l compared with 18.6 ± 1.6 u/l after 4 weeks, respectively (p = 0.03). Conclusion/interpretation: The bisphosphonate, pamidronate, given as a single dose leads to a reduction in bone turnover, symptoms and disease activity in diabetic patients with active Charcot neuroarthropathy. [Diabetologia (2001) 44: 2032–2037] Received: 20 April 2001 and in revised form: 26 June 2001     

Coronary artery injection technique: A quantitative in vivo investigation using modern catheters

To date, there have been no quantitative in vivo assessments of contrast volumes and injection rates using modern high flow catheters during coronary angiography. Contrast volumes (n = 554), injection durations (n = 563), and injection rates (n = 498) were collected during 88 cardiac catheterizations. With increasing cathetersize (6, 7, and 8 French), injection volume increased (P < 0.0001), duration decreased (P < 0.0001), and rate increased (P < 0.0001). Compared with injections into the right coronary artery, left coronary artery injections were larger (7.1 ± 0.1 cc vs. 4.8 ± 0.1 cc, p < 0.0001), longer (3.6 ± 0.05 sec vs 3.0 ± 0.07 sec, P < 0.0001) and faster (2.1 ± 0.04 cc/sec vs. 1.7 ± 0.06 cc/sec, P < 0.0001). Patients with a significant stenosis in the left main or proximal right coronary artery received less contrast (P < 0.0001) more slowly (P < 0.0001) over a similar duration of injection (P = NS). When collaterals arose from the injected artery, angiographers injected more contrast (P < 0.001) over a longer period (P < 0.0001) more slowly (P < 0.0001). Catheter size and the injected vessel's location and anatomy significantly affect coronary catheterization injection technique. Cathet. Cardiovasc. Diagn. 44:34-39, 1998. © 1998 Wiley-Liss, Inc.     

Disability and patient’s appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan

The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify “depressed patients.” A total of 1875 (41.1%) were identified as “depressed patients” who presented with symptoms suggestive of depression. Patient's Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient's VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable “probability of depressed patients.” Patient appraisal of poor general health and greater disability were associated with depressed mood in RA.     

Rotational coronary atherectomy with adjunctive balloon angioplasty for the treatment of ostial lesions

Conventional balloon angioplasty (PTCA) of ostial lesions (OL) is associated with suboptimal results and a higher complication rate. Partial plaque ablation with rotational atherectomy (RA) before PTCA might improve results. This approach was used in 63 patients (pts) (mean age 64±10 yrs; 44 men, 19 women) with 69 OL. There were 15 aorto-OL and 54 branch-OL. Calcification was more frequent in aorto-OL than in branch-OL (67% vs. 35%, P< 0.05). Mean burr size was 1.8±0.3 mm. Burr-artery ratio was 0.74±0.10. Adjunctive PTCA was systematically performed. Procedural success was achieved in 58 pts (92%): 14 aorto-OL (93%) and 50 branch-OL (93%) were successfully treated; major complications occurred in 1 (7%) aorto-OL and 1 (2%) branch-OL. Uncomplicated failure occurred in three cases. Minimal lumen diameter (MLD) increased from 0.69±0.31 mm before RA to 1.43±0.28 mm after RA (P<0.001) and 2.16±0.29 mm after PTCA (P<0.001). Diameter stenosis (DS) decreased from 75±13% before RA to 32±12% after RA (P<0.001) and 14±10% after PTCA (P<0.001). All successfully treated pts underwent repeat angiography 24 h later and exercise testing or repeat cardiac catheterization >6 mo later. At 24 h repeat angiography, DS was 17±15% (P=NS vs. after PTCA); no lesion had a DS ≥ 50%. Follow-up coronary angiography was performed in 30 pts (52%) who had abnormal stress testing: 13 pts (43%) showed angiographic restenosis in at least one successfully treated OL. In conclusion, RA with adjunctive PTCA is a safe and effective treatment of OL. It is associated with higher success and lower major complications rates when compared with conventional PTCA. Restenosis remains a major limitation of all percutaneous approaches. © Wiley-Liss, Inc.