sE‐selectin for stratifying outcome in rheumatoid arthritis

Objectives

To determine the usefulness of sE‐selectin as a marker for early diagnosis and stratification of rheumatoid arthritis.

Methods

We investigated several markers of disease activity, including circulating adhesion molecules and other standard laboratory tests, in a 2–3 year followup analysis of patients with rheumatoid arthritis.

Results

The mean ± SD levels of sE‐selectin (91.68 ± 31.8 ng/ml versus 49.83 ± 14.76 ng/ml) and rheumatoid factor (375.7 ± 394.4 U versus 44.66 ± 37.63 U) were strongly elevated in severe (n = 15) versus mild (n = 7) courses of disease. Statistical calculation of mean and standard deviation revealed that sE‐selectin represents a highly significant marker for the presence of persistent and aggressive disease over time, regardless of therapeutic intervention and observation time points (P = 0.0004). Notably, regression analysis identified constant values for all parameters analyzed and, therefore, a stable course of the disease could be predicted from the beginning.

Conclusion

sE‐selectin appears to be a powerful marker to predict the severity of rheumatoid arthritis.

     

Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in men with combined hyperlipidaemia

Hoogerbrugge N, Kerkhofs LGN, Jansen H (University Hospital Dijkzigt, Rotterdam, The Netherlands). Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in men with combined hyperlipidaemia. J Intern Med 1998; 243 : 355–59.

Objectives

Gemfibrozil is the most widely used fibric acid for the management of combined hyperlipidaemia. It has beneficial effects in the prevention of coronary heart disease (CHD). The mechanisms by which it exerts this effect are not completely resolved. We studied whether gemfibrozil affects low-density lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate combined hyperlipidaemia at high risk for progressive atherosclerosis.

Design

Open treatment with 2 × 600 mg gemfibrozil daily for 12 weeks.

Setting

Outpatient lipid clinic of a tertiary referral centre.

Subjects

Twenty-three patients with combined hyperlipidaemia and CHD or a positive family history for both CHD and hyperlipidaemia.

Main outcome measures

Effects on triglyceride (TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative modification.

Results

During treatment with gemfibrozil, plasma TG concentration decreased from 2.83 ± 0.85 to 2.02 ± 0.89 mmol L^?1 (P < 0.001). All but one patient were shown to have LDL pattern B. The LDL pattern did not change upon treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime during in-vitro oxidation slightly decreased from 105 ± 22 to 99 ± 18 min (P= 0.01). The concentration of autoantibodies against oxidized LDL indicates the rate of LDL oxidation in vivo. This concentration significantly decreased from 14.2 ± 9.9 to 13.1 ± 9.2 mg L^?1 (P < 0.01).

Conclusions

The beneficial effect of gemfibrozil in reducing CHD may at least in part depend on a decrease of the rate of LDL oxidation in vivo.

     

Health‐related quality of life in juvenile‐onset systemic lupus erythematosus and its relationship to disease activity and damage

Objective

To assess the health‐related quality of life (HRQL) of patients with juvenile‐onset systemic lupus erythematosus (JSLE) and its relationship with disease activity and accumulated damage.

Methods

In this cross‐sectional study, HRQL was assessed using the Child Health Questionnaire (CHQ), disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and accumulated damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).

Results

A total of 297 patients were included. The mean ± SD physical and psychosocial summary scores of the CHQ were 40.2 ± 15.0 and 44.8 ± 10.7, respectively. The most impaired CHQ subscales were global health, general health perceptions, and parent impact–emotional. The SLEDAI score was significantly correlated with both the physical summary score (r = ?0.29, P < 0.0001) and psychosocial summary score (r = ?0.25, P < 0.0001), whereas the SDI score was significantly correlated only with the physical summary score (r = ?0.23, P = 0.0001).

Conclusion

We found that patients with JSLE have significant impairment of their HRQL, particularly in the physical domain. HRQL may be affected by both disease activity and accumulated damage, particularly in the renal, central nervous, and musculoskeletal systems.

     

Anaerobic exercise capacity in patients with juvenile‐onset idiopathic inflammatory myopathies

Objective

To 1) report the feasibility of an “all‐out” 30‐second cycling exercise test (Wingate Anaerobic Exercise Test [WAnT]) in juvenile‐onset idiopathic inflammatory myopathy (JIIM) patients, 2) describe the anaerobic exercise capacity in juvenile dermatomyositis patients, and 3) determine if the anaerobic exercise capacity could be related to disease duration or disease phase.

Methods

Twenty patients (age 14.13 ± 5.4 years) with JIIM participated in this study. All patients were able to perform the WAnT without adverse events.

Results

Comparison with healthy controls revealed a ?29.3 ± 26.58% (P = 0.001) and ?27.6 ± 25.7% (P = 0.002) impairment in mean power and peak power on the WAnT, respectively. The WAnT correlated with disease phase and with knee extensor muscle strength.

Conclusion

The WAnT might be a valuable adjunct next to other assessment tools in the followup of JIIM patients.

     

High‐sensitivity C‐reactive protein,disease activity,and cardiovascular risk factors in systemic lupus erythematosus

Objective

To study the level of high‐sensitivity C‐reactive protein (hsCRP) and its relationship with disease activity, damage, and cardiovascular risk factors in patients with systemic lupus erythematosus (SLE).

Methods

Consecutive patients who fulfilled ≥4 American College of Rheumatology criteria for SLE who did not have a concurrent infection were recruited. Blood was assayed for hsCRP level, and disease activity, organ damage of SLE, and cardiovascular risk factors were assessed. Linear regression analyses were performed for the relationship between hsCRP levels, SLE activity, damage, and cardiovascular risk factors.

Results

In total, 289 patients were studied (94% women, mean ± SD age 39.0 ± 13.1 years, and mean ± SD SLE duration 7.8 ± 6.7 years). The mean ± SD Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 4.9 ± 5.6 and clinically active SLE was present in 122 patients (42%). The mean ± SD hsCRP level was 4.87 ± 12.7 mg/liter, and 28 patients with active SLE (23%) had an undetectable hsCRP level (<0.3 mg/liter). The linear regression analyses revealed a significant correlation between hsCRP level and musculoskeletal disease (β = 0.21), hematologic disease (β = 0.19), active serositis (β = 0.46), and clinical SLEDAI score (β = 0.24) after adjusting for age, sex, body mass index, serum creatinine, and the use of various medications (P < 0.005 for all). hsCRP levels correlated significantly with anti–double‐stranded DNA titer (β = 0.33, P < 0.001) but did not correlate with complement C3 (β = ?0.07, P = 0.26). An hsCRP level >3 mg/liter was significantly associated with male sex, long‐term smoking, diabetes mellitus, a higher atherogenic index, and a history of arterial thrombosis. hsCRP levels correlated significantly with pulmonary and endocrine damage scores.

Conclusion

hsCRP was detectable in 77% of SLE patients with clinically active disease and correlated with SLEDAI scores, particularly in serositis and in the musculoskeletal and hematologic systems. Elevated hsCRP levels in SLE were associated with certain cardiovascular risk factors and a history of arterial thromboembolism.

     

Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine

Florén C-H, Ahrén B, Bengtsson M, Bartosik J, Obrant K (Lund University, Malmö, Sweden). Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine. J Intern Med 1998; 243 : 123–26.

Objectives

To ascertain whether patients with Crohn's disease treated with azathioprine maintained bone mineral mass better than patients treated with steroids alone.

Design

Retrospective study.

Setting

University Hospital of Malmö, Sweden.

Subjects

A total of 59 patients with ileocolonic, ileocaecal or colonic Crohn's disease.

Methods

Bone mass was assessed by dual photon X-ray absorptiometry at the level of L2 – L4.

Results

Patients treated with a high lifetime dose of steroids (> 5 g prednisolone) had significantly (P= 0.011) lower Z-score of L₂–L₄ (?0.87 ± 1.11; 11 SD) than steroid-treated patients, who had received a low dose of prednisolone (< 5 g) (0.08 ± 1.16 SD). Azathioprine did not negatively influence the steroid effect on bone mineral density.

Conclusions

Azathioprine does not seem to affect bone mineral density by itself. However, by being steroid-saving, it seems to conserve bone mineral mass in patients with Crohn's disease.

     

Brief Report: Shortened Telomere Length in Patients With Systemic Lupus Erythematosus

Objective

Patients with systemic lupus erythematosus (SLE) have a higher rate of premature death compared to the general population, suggesting a phenotype of premature senescence in SLE. Telomere length can be used to assess overall biologic aging. This study was undertaken to address the hypothesis that patients with SLE have reduced telomere length.

Methods

Telomere length was measured cross‐sectionally in whole blood from SLE patients and age‐matched healthy female controls, using real‐time quantitative polymerase chain reaction. SLE‐related and cardiovascular risk factors were assessed.

Results

We compared telomere length in 63 SLE patients and 63 matched controls with a median age of 50.8 years (interquartile range [IQR] 37–59 years) and 49.9 years (IQR 32–60 years), respectively. The median relative telomere length in SLE patients was 0.97 (IQR 0.47–1.57), compared to 1.53 (IQR 0.82–2.29) in controls (P = 0.0008). We then extended our cohort to measure telomere length in 164 SLE patients. Shorter telomere length was associated with Ro antibodies (β ± SE −0.36 ± 0.16; P = 0.023), and longer telomere length was associated with steroid therapy (0.29 ± 0.14; P = 0.046). We also noted an association of longer telomere length with increasing body mass index (β ± SE 0.07 ± 0.01; P < 0.0001) and tobacco smoking (0.64 ± 0.26; P = 0.016), as well as with the presence of carotid plaque (0.203 ± 0.177; P = 0.032).

Conclusion

Telomere length is shortened in SLE patients compared to controls and does not appear to be a reflection of disease activity or immune cell turnover. Subsets of patients such as those positive for Ro antibodies may be particularly susceptible to premature biologic aging. The predictive value of telomere length as a biomarker of future risk of damage/mortality in SLE requires longitudinal evaluation.

     

Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and degree of coronary artery disease

Regnström J, Jovinge S, Båvenholm P, Ericssond C-G, de Faire U, Hamsten A, Hellenius M-L, Nilsson J, Tornvall P (Karolinska Hospital and Danderyd Hospital, Stockholm, Sweden). Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and coronary artery disease. J Intern Med 1998; 243 : 109–13.

Objectives

To determine the prevalence of chronic infection with Helicobacter pylori (HP) in patients with established coronary artery disease (CAD) and in healthy controls. Furthermore, to investigate whether HP infection is associated with inflammatory parameters, lipid concentrations and degree and progression of CAD.

Design

A case–control study combined with a prospective angiographic study.

Setting

Stockholm Metropolitan Area, Sweden.

Patients and methods

A material consisting of 92 young men aged 40.9 ± 3.2 (mean ± SD) years, with previous myocardial infarction and documented coronary atherosclerosis, and 95 healthy sex-matched controls, aged 43.2 ± 3.0 (mean ± SD) years, with similar socio-economic status and ethnic background was analysed for the prevalence of HP seropositivity, plasma concentrations of the inflammatory parameters fibrinogen, tumour necrosis factor alpha and orosomucoid, and serum concentrations of lipids. The impact of HP seropositivity on degree and progression of CAD, as assessed by quantitative coronary angiography, was also determined.

Results

The study population of mainly Scandinavian origin had a low prevalence of HP seropositivity in comparison with previously published European populations. No significant increase in HP seropositivity was found in patients compared with controls (42.2 vs. 32.6%). Furthermore, HP infection was not associated with increased levels of inflammatory parameters, lipid concentrations or with degree of angiographically determined CAD at baseline, or progression of CAD and clinical events over 5 years.

Conclusions

HP infection is not associated with inflammatory parameters and lipid concentrations and could not be confirmed as a risk factor for CAD.

     

Low circulating leptin levels in protein-energy malnourished chronically ill elderly patients

Cederholm T, Arner P, Palmblad J (Karolinska Institute at the Centre for Inflammation & Hematology Research, and Huddinge University Hospital, Huddinge, Sweden). Low circulating leptin levels in protein-energy malnourished chronically ill elderly patients. J Intern Med 1997; 242 : 377–82.

Objective

To evaluate serum leptin, a fat cell-derived protein, levels in relation to the malnutrition often observed in chronic disease.

Design

A comparison of circulating leptin concentrations in malnourished chronically ill elderly and in age-matched controls.

Setting

A university-affiliated teaching hospital in Stockholm, Sweden.

Subjects

Nineteen protein–energy malnourished elderly patients (74 ± 1 years) with various chronic nonmalignant diseases and 18 healthy controls (72 ± 1 years).

Main outcome measures

Serum leptin levels measured by radioimmunoassay technique, nutritional status as expressed by body mass index (kg m^?2), triceps skin fold, arm muscle circumference and serum albumin, and serum orosomucoid concentrations indicating inflammatory status.

Results

Patients and controls displayed body mass indexes of 17.4 ± 0.7 and 25.0 ± 1.1 (P < 0.001), respectively. Triceps skin fold (TSF) measurements revealed a pronounced fat depletion in the patients, being 8.5 ± 0.9 and 22.3 ± 1.5 mm (P < 0.001) in female and 6.1 ± 0.7 and 10.8 ± 0.8 mm (P < 0.001) in male patients and controls, respectively. Patient serum leptin concentrations were less than half of the corresponding concentrations in the controls, 4.3 ± 1.1 and 9.3 ± 1.3 ng mL^?1 (P < 0.01), respectively. The highest leptin concentrations were registered in female controls, 12.1 ± 1.6 ng mL^?1. The serum leptin levels in the controls correlated with TSF (r= 0.74; P < 0.001). No such correlation was found in the patients.

Conclusions

Serum leptin levels were low and did not seem to be directly associated with fat and muscle depletion in elderly patients with chronic illness, whereas they appeared to be positively correlated to body fat in healthy elderly.

     

ACE,PAI‐1, decorin and Werner helicase genes are not associated with the development of renal disease in European patients with Type 1 diabetes

Background

Genetic factors are involved in the development of diabetic nephropathy in Type 1 diabetes. We have examined the association of four candidate genes, angiotensin converting enzyme (ACE): insertion/deletion (I/D) polymorphism, plasminogen activator inhibitor‐1 (PAI‐1): 4G/5G polymorphism, decorin: 179/183/185 polymorphism and Werner syndrome helicase: C/R polymorphism, with the presence of diabetic nephropathy in Type 1 diabetic patients.

Methods

175 Type 1 diabetic patients with albuminuria (59 with microalbuminuria and 116 with macroalbuminuria) were compared with 136 Type 1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years (mean±SD: 25±8 years). 200 non‐diabetic subjects were also studied as background population.

Results

We found no association in the polymorphism of the four genes examined between patients with and without diabetic nephropathy and the control subjects.

Conclusions

The genes studied are unlikely to be involved in the susceptibility to nephropathy in Type 1 diabetic patients. Copyright © 1999 John Wiley & Sons, Ltd.

     

Vitamin A deficiency alters airway resistance in children with acute upper respiratory infection

Objective

To assess whether vitamin A deficiency alters the recovery of total respiratory resistance (TRR) following acute upper respiratory tract infection (URI).

Methods

This is a case control study of children, age 4–6 years and grouped as: URI, (n = 74), URI and wheezing, (URI‐wheezing, n = 52), and healthy controls (n = 51). Vitamin A and total respiratory resistance (TRR) were assessed using the modified relative dose response (MRDR) and forced oscillometry, respectively.

Results

Children with URI and URI‐wheezing had lower retinol, 32.4 ± 13.12 and 18.3 ± 6.83 µg/dl respectively, compared to controls, 56.9 ± 29.82 µg/dl (ANOVA, P < 0.001). The MRDR was elevated in children in the URI or URI‐wheezing groups 0.066 ± 0.045 and 0.021 ± 0.021, respectively, compared to controls 0.007 ± 0.006 (ANOVA, P < 0.0001). The TRR in the URI and URI‐wheezing groups differed from controls. During convalescence, the TRR failed to decline in the URI‐group only when the MRDR was >0.06. In the URI‐wheezing group, TRR declined independently of retinol and MRDR.

Conclusion

Vitamin A contributes to preservation of airway function during and in recovery after upper respiratory infection in children. Pediatr Pulmonol. 2013; 48:481–489. © 2012 Wiley Periodicals, Inc.

     

Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: A randomized,double‐blind,placebo‐controlled trial in asymptomatic antiphospholipid antibody–positive individuals

Objective

To determine the efficacy of a daily dose of 81 mg aspirin in primary thrombosis prevention in asymptomatic, persistently antiphospholipid antibody (aPL)–positive individuals (those with positive aPL but no vascular and/or pregnancy events).

Methods

The Antiphospholipid Antibody Acetylsalicylic Acid (APLASA) study was a multicenter, randomized, double‐blind, placebo‐controlled clinical trial in which asymptomatic, persistently aPL‐positive individuals were randomized to receive a daily dose of 81 mg of aspirin or placebo. In a separate observational and parallel study, asymptomatic, persistently aPL‐positive individuals who were taking aspirin or declined randomization were followed up prospectively.

Results

In the APLASA study, 98 individuals were randomized to receive aspirin or placebo (mean ± SD followup period 2.30 ± 0.95 years), of whom 48 received aspirin and 50 received placebo. In the observational study, 74 nonrandomized individuals were followed up prospectively (mean ± SD followup period 2.46 ± 0.76 years); 61 received aspirin and 13 did not. In the APLASA study, the acute thrombosis incidence rates were 2.75 per 100 patient‐years for aspirin‐treated subjects and 0 per 100 patient‐years for the placebo‐treated subjects (hazard ratio 1.04, 95% confidence interval 0.69–1.56) (P = 0.83). Similarly, in the observational study, the acute thrombosis incidence rates were 2.70 per 100 patient‐years for aspirin‐treated subjects and 0 per 100 patient‐years for those not treated with aspirin. All but 1 patient with thrombosis in either study had concomitant thrombosis risk factors and/or systemic autoimmune disease at the time of thrombosis.

Conclusion

Our results suggest that asymptomatic, persistently aPL‐positive individuals do not benefit from low‐dose aspirin for primary thrombosis prophylaxis, have a low overall annual incidence rate of acute thrombosis, and develop vascular events when additional thrombosis risk factors are present.

     

Is there an alternative to the full‐leg radiograph for determining knee joint alignment in osteoarthritis?

Objective

To assess the concurrent validity of alternative measures of frontal plane knee alignment, namely the radiographic anatomic axis and 5 clinical measures, in medial compartment knee osteoarthritis (OA) as compared with the mechanical axis on radiograph.

Methods

Forty individuals (mean ± SD age 64.7 ± 9.4 years) with symptomatic medial knee OA participated. Knee alignment was measured according to the following methods: lower‐limb mechanical axis on radiograph, lower‐limb anatomic axis on radiograph, visual observation, distance between medial knee joint lines or medial malleoli using a calliper, distance between a plumb line and medial knee joint line or malleolus using a calliper, tibial alignment using a gravity inclinometer, and lower‐limb alignment using a goniometer. Data were analyzed using Pearson's correlation coefficient or Spearman's rho correlation coefficient and simple linear regression.

Results

The anatomic axis best correlated with the mechanical axis (r = 0.88), followed closely by the inclinometer method (r = 0.80). Other clinical measures of alignment that were significantly associated with the mechanical axis were the calliper method, the plumb‐line method, and visual observation (r = 0.76, 0.71, and ?0.52, respectively). However, the goniometer method failed to correlate.

Conclusion

The anatomic axis on radiograph and the inclinometer method appear to be valid alternatives to the mechanical axis on full‐leg radiograph for determining frontal plane knee alignment in medial knee OA. These alternative methods of measuring knee alignment may increase the assessment of this parameter by clinicians and researchers alike, given that malalignment is an important indicator of disease progression and treatment outcome.

     

Assessing utility values in rheumatoid arthritis: A comparison between time trade‐off and the EuroQol

Objective

To compare the utility values and quality‐adjusted life years (QALYs) obtained by the Time Trade‐Off instrument (TTO) and the EuroQol‐5D (EQ‐5D) in patients with rheumatoid arthritis (RA); to analyze the association between utility values and Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ).

Methods

We conducted a longitudinal, prospective, 1‐year study of RA patients selected randomly from 10 rheumatology clinics. TTO and EQ‐5D were administered at 4 scheduled visits.

Results

The study sample comprised 300 RA patients (82% women, mean age 59 years, mean disease duration 10.3 years). A total of 260 patients completed both the TTO and the EQ‐5D at baseline, and the mean ± SD TTO scores were significantly higher than the EQ‐5D scores (0.81 ± 0.22 versus 0.53 ± 0.35, P < 0.0001). The intraclass correlation coefficient (ICC) for the utility methods was 0.19. Data about changes in both TTO and EQ‐5D scores during the study year were available in 163 patients. These changes tended to be larger in the TTO scores than the EQ‐5D scores (mean ± SD 0.05 ± 0.25 versus ?0.005 ± 0.35, P = 0.054). The ICC for the mean changes in the utility scores was 0.24. Patients obtained a mean ± SD of 0.04 ± 0.20 QALYs based on TTO scores and 0.004 ± 0.27 based on EQ‐5D scores (P = 0.12). At baseline, the EQ‐5D scores were highly correlated with the HAQ (r = ?0.74) and moderately correlated with the DAS28 (r = ?0.47), whereas the TTO correlated poorly with both the HAQ and DAS28. Correlation between the mean change in the EQ‐5D and in the HAQ was moderate (r = ?0.55).

Conclusion

TTO and EQ‐5D do not yield the same utility values. The results suggest that the EQ‐5D is more representative of RA status than the TTO, a valuable conclusion when addressing economic evaluations in RA.

     

Anti–tumor necrosis factor agents for rheumatoid arthritis in the setting of chronic hepatitis C infection

Objective

To examine the safety of using anti–tumor necrosis factor (TNF) therapy in patients with rheumatoid arthritis (RA) in the setting of hepatitis C virus (HCV) infection.

Methods

The charts of 5 patients known to have RA requiring anti‐TNF therapy as well as established HCV infection were reviewed retrospectively for laboratory data of hepatic parenchymal inflammation and viral proliferation while taking these agents.

Results

In a mean ± SD followup period of 41 months (± 28.2 months), no patient displayed evidence of sustained elevation of serum aminotransferases during therapy with anti‐TNF. Additionally, 1 patient was observed to have a decreased HCV viral load after extended treatment with only anti‐TNF (no therapy for HCV).

Conclusion

Anti‐TNF therapy for RA in the setting of HCV appears to be safe and well tolerated without apparent influence on the underlying HCV infection. Therefore, this approach should be further evaluated prospectively for longterm safety.

     

Measurement of varus/valgus alignment in obese individuals with knee osteoarthritis

Objective

Frontal plane knee malalignment may increase progression of knee osteoarthritis (OA) and hasten functional decline. An accurate nonradiographic measure of knee alignment is necessary because the gold standard measure, the long‐leg radiograph, is costly and often unavailable. Moreover, nonradiographic measures of knee alignment have not been validated in an obese population, where knee OA is common. The purpose of this study was to develop and assess the concurrent validity and reliability of a nonradiographic measure of frontal plane knee alignment and demonstrate the accuracy of the measure in an obese population.

Methods

Fifty‐five subjects (41 women, 14 men; mean ± SD age 62.9 ± 10.3 years) with knee OA were examined. A nonradiographic measure (umbilical method) of frontal plane alignment, using the landmarks of the umbilicus, knee, and ankle, was compared with the radiograph gold standard. Statistical significance was accepted at P < 0.05.

Results

Eighty‐nine percent of the participants had a body mass index (BMI) placing them in the overweight or obese category (mean ± SD BMI for all subjects 31.3 ± 6.1 kg/m²). Radiographic measures of alignment ranged from 9.1° valgus to 14.3° varus (76% of the participants had varus alignment, 12% had valgus alignment, and 2% had neutral alignment). Umbilical measures ranged from 1° valgus to 21° varus. The umbilical measure was significantly correlated with the radiographic method (r = 0.75, P < 0.001). The error of the umbilical measure was not significantly correlated with the BMI (r = ?0.21, P = 0.13).

Conclusion

The umbilical method of assessing frontal plane knee alignment is a valid surrogate for the radiographic gold standard and retains its accuracy in an obese population.

     

Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease

Valdemarsson S, Lindergård B, Tibblin S, Bergenfelz A (Lund University Hospital, Sweden). Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease. J Intern Med 1998; 243 : 115–22.

Objectives

.To evaluate the impact on bone turnover of primary hyperparathyroidism (pHPT) with special reference to patients with mild pHPT, using biochemical markers of bone formation and resorption.

Design

.A longitudinal study of patients with pHPT before and one year after surgical treatment.

Setting

.The Departments of Internal Medicine and Surgery, Lund University Hospital.

Subjects

.Forty consecutive patients with pHPT. Thirty of these patients had mild pHPT and are reported separately. Data on bone mineral was also compared to a reference population.

Intervention

All patients were operated upon and restudied one year later.

Main outcome measures

.Bone resorption and formation was studied by means of the serum concentrations of the telopeptide of the carboxyterminal region of type 1 collagen (ICTP) and of alkaline phosphatase (ALP), osteocalcin and the carboxyterminal propeptide of type 1 procollagen (PICP), respectively. Bone density was measured at the distal radius by single photon absorptiometry (SPA).

Results

.Bone formation markers consistenly decreased after parathyroid surgery: ALP from 3.51 ± 0.23 to 2.94 ± 0.21 µkat L^?1 (P < 0.05), osteocalcin from 6.15 ± 0.53 to 2.89 ± 0.23 µg L^?1 (P < 0.001) and PICP from 126.4 ± 10.9 to 96.0 ± 6.5 µg L^?1 (P < 0.001). In parallel, the ICTP concentration, reflecting bone resorption, decreased from 5.10 ± 0.54 to 3.94 ± 0.34 µg L^?1 (P < 0.001). There was not any significant change in distal radius bone mineral 1 one year after surgery. In the subgroup of patients classified as mild pHPT, a significant decrease was noted for osteocalcin, PICP and for ICTP but not for ALP, without significant changes in variables reflecting distal radius bone mineral content. Glomerular filtration rate was inversely correlated to serum levels of intact PTH, ionized calcium, alkaline phosphatase, osteocalcin and ICTP and directly correlated to the 1.25-dihydroxy-vitamin D concentrations.

Conclusions

.pHPT is associated with substantial changes in circulating levels of biochemical markers of bone formation and resorption. These findings are also present in patients with mild pHPT. Renal function should be considered in the evaluation of the impact of pHPT on bone turnover.

     

Neuromuscular fatigue and exercise capacity in fibromyalgia syndrome

Objective

To assess quadriceps strength and fatigability by using femoral nerve magnetic stimulation (FNMS) and their relationship to exercise capacity in patients with fibromyalgia syndrome (FMS) and healthy controls.

Methods

Twenty‐two women (11 with FMS, 11 controls) performed a maximal incremental cycling test and a quadriceps fatigue test on 2 separate visits. For quadriceps assessment, we used FNMS during and after maximum voluntary contraction (MVC) to evaluate central and peripheral factors of neuromuscular fatigue. Subjects performed sets of 10 intermittent (5 seconds on/5 seconds off) isometric contractions starting at 10% MVC, in 10% MVC increments from one set to another until exhaustion. Neuromuscular fatigue was assessed with FNMS after each set.

Results

FMS patients had reduced initial MVC compared to controls (mean ± SD 102 ± 18 versus 120 ± 24 Nm; P < 0.05) without significant impairment of voluntary activation (mean ± SD 93.5% ± 3.0% versus 93.1% ± 3.4%; P = 0.74). During the fatigue task, FMS patients exhibited a greater fall in evoked muscular responses (mean ± SD ?26% ± 6% versus ?16% ± 8% at set 50% MVC; P < 0.05), but not in MVC (mean ± SD ?24% ± 7% versus ?19% ± 4% at set 50% MVC; P = 0.12). During the cycling test, FMS patients had lowered maximal exercise capacity and an enhanced rate of perceived exertion (RPE) compared to controls. The percent reduction in evoked muscular responses during the quadriceps fatigue test correlated with maximum oxygen consumption (r = 0.56, P < 0.05) and RPE at submaximal intensity (r = 0.84, P < 0.05) during cycling.

Conclusion

Greater impairment in muscle contractility is associated with enhanced perception of exertion and reduced maximal exercise capacity in FMS patients. Neuromuscular impairments should be considered as an important factor underlying functional limitations in FMS patients.

     

When it hurts,a positive attitude may help: association of positive affect with daily walking in knee osteoarthritis. Results from a multicenter longitudinal cohort study

Objective

While depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association.

Methods

This study is a cross‐sectional analysis of the Multicenter Osteoarthritis Study. We included 1,018 participants (mean ± SD age 63.1 ± 7.8 years, 60% women) who had radiographic knee OA and had worn a StepWatch monitor to record their number of steps per day. High and low positive affect and depressive symptoms were based on the Center for Epidemiologic Studies Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screening.

Results

Compared to respondents with low positive affect (27% of all respondents), those with high positive affect (63%) walked a similar number of steps per day, while those with depressive symptoms (10%) walked less (adjusted β ?32.6 [95% confidence interval (95% CI) ?458.9, 393.8] and ?579.1 [95% CI ?1,274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (P = 0.0045). Among the respondents with knee pain (39%), those with high positive affect walked significantly more steps per day (adjusted β 711.0 [95% CI 55.1, 1,366.9]) than those with low positive affect.

Conclusion

High positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider for promoting physical activity among people with painful knee OA.

     

Severe valvular regurgitation and antiphospholipid antibodies in systemic lupus erythematosus: A prospective,long‐term,followup study

Objective

To assess whether the presence of antiphospholipid antibodies is related to the incidence and progression of severe valvular dysfunction and the need for valve replacement in patients with systemic lupus erythematosus (SLE).

Methods

In this prospective, long‐term followup study, the initial echocardiographic findings in a cohort of 61 consecutive SLE patients were compared with those of 40 matched controls. All patients were serially evaluated for 14 ± 3 years and had a followup echocardiogram 8 ± 3 years after the initial evaluation. Serial determinations of anticardiolipin antibodies and lupus anticoagulant were performed in all cases.

Results

The number of SLE patients with valvular abnormalities increased from 39% to 73% between the initial and the followup echocardiography, but only 7 patients (12%) developed severe valvular regurgitation. Severe valvular regurgitation was significantly associated with the presence of high levels of IgG anticardiolipin antibodies (P = 0.001). The combined incidence of stroke, peripheral embolism, need for valve surgery, and death was 86% in patients with severe valvular regurgitation, compared with 25% in those without (P = 0.003).

Conclusion

In SLE patients, the presence of high levels of IgG anticardiolipin antibodies is associated with the development of severe valvular regurgitation and with a high incidence of thromboembolic events and the need for valvular surgery.