Assessment of aortic stiffness and ventricular diastolic functions in patients with Behçet’s disease

Background: Behçets disease is a systemic vasculitis in which studies have given conflicting results about ventricular diastolic functions. However, tissue Doppler echocardiography has never been used in any of these studies. Aortic stiffness, a cardiovascular risk factor, may also precede ventricular dysfunction. Objectives: The aim of this study was to assess aortic stiffness and biventricular diastolic functions in patients with Behçets disease. Methods: A total of 26 patients with Behçets disease (mean age; 33±10 years) and 20 age- and sex-matched controls (mean age; 33±7 years) were included. Aortic stiffness was evaluated by aortic strain and distensibility. Ventricular diastolic functions were evaluated with both conventional and tissue Doppler echocardiography. Mitral E and A wave, E/A ratio of E wave, deceleration time, and isovolumic relaxation time were calculated. Results: There was no significant difference in diastolic Doppler parameters between patients and controls. Similarly, there was no significant difference in mitral annular E and A velocities between these two groups. Aortic strain in patients with Behçets disease was found to be significantly less than in the controls (8.3±4.9% and 15.7±2.7% respectively, p<0.001). Aortic distensibility was also significantly low in patients with Behçets disease when compared to controls (0.45±0.28 and 0.78±0.13 respectively, p<0.001). Beta index values were significantly high in Behçets patients (7.23±5.93 and 2.69±0.55 respectively, p<0.001). Conclusion: No significant diastolic dysfunction was found in left and right ventricles in patients with Behçets disease by using both conventional and tissue Doppler echocardiography. However, an increase in aortic stiffness was found, suggesting an inflammatory involvement of proximal aorta.     

Efficacy of Topical Metronidazole (10 Percent) in the Treatment of Anorectal Crohn’s Disease

PURPOSE The aim of this study was to investigate the efficacy of 10 percent topical metronidazole in the treatment of symptomatic anorectal Crohns disease.METHODS Patients with symptomatic anorectal Crohns disease were studied in a prospective, nonblinded, nonrandomized study to evaluate the efficacy of topical 10 percent metronidazole. Perianal Crohns Disease Activity Index and each component (pain, discharge, induration, sexual dysfunction, and type of pathology) were recorded before treatment and at four weeks. Visual analog pain score (0–10) was recorded before treatment and at weekly intervals for up to four weeks.RESULTS Fourteen patients were studied prospectively for four weeks. Mean Perianal Crohns Disease Activity Index decreased from 8.8 ± 0.9 before treatment to 4.1 ± 0.7 after four weeks treatment (P < 0.0001). Visual analog pain scores decreased from 5.4 ± 0.7 before treatment to 2.4 ± 0.5 at one week (P < 0.001) and to 1.0 ± 0.4 after four weeks treatment (P < 0.0001). Of the Perianal Crohns Disease Activity Index components, significant decreases were noted in pain and discharge (P < 0.0001) and induration (P < 0.001).CONCLUSION For patients with perianal Crohns disease, topical 10 percent metronidazole decreases the Perianal Crohns Disease Activity Index and anorectal pain.     

El síndrome de apneas-hipoapneas del sueño (SAHS) grave incrementa la excreción urinaria de eritropoyetina. Efecto del tratamiento con CPAP

Introduction

Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep.

Consistencia interna y validez de la versión española del cuestionario de calidad de vida específico para el síndrome de apnea del sueño: Sleep Apnoea Quality of Life Index

Introduction

The objective of the present study was to validate the Spanish version of the SAQLI, which is a health-related quality of life (HRQL) questionnaire specific for sleep apnea-hypopnea syndrome (SAHS), and to assess its sensitivity to change.

Material and methods

A multicenter study performed in a group of patients with SAHS (apnea-hypopnea index [AHI] ≥5) who had been referred to the centers’ Sleep Units. All patients completed the following questionnaires: SF-36, FOSQ, SAQLI and Epworth scale. The psychometric properties (internal consistency, construct validity, concurrent validity, predictive value, repeatability and responsiveness to change) of the SAQLI were assessed (four domains: daily function, social interactions, emotional function and symptoms; an optional fifth domain is treatment-related symptoms).

Results

One hundred sixty-two patients were included for study (mean age: 58 ± 12; Epworth: 10 ± 4; BMI: 33 ± 5.9 kg m⁻²; AHI: 37 ± 15 hour⁻¹). The factorial analysis showed a construct of four factors with similar distribution to the original questionnaire domains. Internal consistency (Cronbach's alpha between 0.78 and 0.82 for the different domains), concurrent validity for SF-36, Epworth scale and FOSQ, and test-retest reliability were appropriate. The predictive validity of the questionnaire showed no significant correlations with the severity of SAHS. SAQLI showed good sensitivity to change in all the domains of the questionnaire (p < 0,01).

Conclusions

The Spanish version of the SAQLI is a valid HRQL measurement with appropriate psychometric properties for use in patients with SAHS and it is sensitive to change.     

Do obstructive sleep apnea syndrome patients underestimate their daytime symptoms before continuous positive airway pressure treatment?

BACKGROUND:

Daytime somnolence is an important feature of the obstructive sleep apnea (OSA) hypopnea syndrome and is usually subjectively assessed using the Epworth Sleepiness Scale (ESS).

OBJECTIVE:

To compare the scores of the ESS and different domains of the Quebec Sleep Questionnaire (QSQ) assessed before and after the first months of continuous positive airway pressure (CPAP) treatment, as well as retrospectively without treatment.

METHODS:

The ESS score and domain scores of the QSQ were obtained before and after a three-month period of CPAP treatment using a retrospective assessment of the pretreatment scores in 76 untreated OSA patients.

RESULTS:

Fifty-two patients completed the study. The ESS and QSQ scores significantly improved following CPAP therapy. Retrospective evaluation of the ESS score was significantly worse than pre- and post-treatment values (mean [± SD] pretreatment score 11.0±4.8; retrospective pretreatment score 13.5±5.1). Such differences were not observed in any domain of the QSQ, including the domain assessing hypersomnolence.

CONCLUSION:

OSA patients underestimated their sleepiness according to the most widely used instrument to assess hypersomnolence. This finding may not be observed with other methods used to assess OSA-related symptoms such as quality of life questionnaires.     

Twenty-four hour profiles of plasma C-peptide in Type 1 (insulin-dependent) diabetic children

Summary Twenty-four hour profiles of plasma C-peptide an index of endogenous insulin secretion, were performed in 15 Type 1 (insulin-dependent) diabetic children. Plasma C-peptide was detectable in six children, of whom four (C-peptide producers) had peak values above normal fasting levels. In each of the six children with residual B cell function, there was a close correlation between plasma C-peptide and simultaneous blood glucose (r> 0.50, p< 0.05). Post-breakfast peak blood glucose was 10.2 ± 1.7 mmol/l (mean ±SEM) in the C-peptide producers and 18.7 ± 1.7 mmol/l in the 11 children with low or no detectable C-peptide. Mean M-value, an index of deviation from an ideal blood glucose, was lower in the C-peptide producers (p<0.05). It is concluded that residual functioning B cells in diabetic children behave physiologically in that insulin secretion fluctuates in accordance with the prevailing blood glucose; and that the pattern of action of injected insulin is more critical in non-C-peptide producers who lack the post-prandial dampening effect provided by residual endogenous insulin secretion.     

Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome

Arterial blood pressure rises at apnea termination, and there is increasing evidence that the sleep apnea-hypopnea syndrome (SAHS) is associated with daytime hypertension but no randomized controlled trial evidence of whether SAHS treatment reduces blood pressure exists. We, therefore, conducted a randomized placebo-controlled cross-over study of the effects of 4 wk of continuous positive airway pressure (CPAP) or oral placebo on 24-h blood pressure in 68 patients (55 males, 13 females; median apnea-hypopnea index [AHI], 35) not receiving hypotensive medication. Ambulatory blood pressure was recorded for the last 48 h of each treatment. Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also recorded. All patients were normotensive. There was a small decrease in 24-h diastolic blood pressure (placebo, 79.2 [SE 0.9] mm Hg; CPAP, 77.8 [SE 1.0] mm Hg; p = 0.04) with the greatest fall occurring between 2:00 A.M. and 9:59 A.M. The observed decrease in 24-h diastolic blood pressure was greater in two a priori groups, CPAP use > or = 3.5 h per night (81.5 [SE 1.2] mm Hg; 79.6 [SE 1.2] mm Hg; p = 0.03) and those with more than twenty 4% desaturations per hour (82.4 [SE 2.1] mm Hg; 77.4 [SE 2.1] mm Hg; p = 0.002). Systolic pressure also fell in the latter group (133.1 [SE 2.8] mm Hg; 129.1 [SE 2.1] mm Hg; p = 0.009). Desaturation frequency was the best predictor of diastolic blood pressure fall with CPAP (r = 0.38; p = 0.002). Both ESS and FOSQ domains improved. Thus, CPAP can reduce blood pressure in patients with SAHS, particularly in those with nocturnal oxygen desaturation, but the decrease is small.     

Vitamin C therapy ameliorates vascular endothelial dysfunction in treated patients with homocystinuria

Objectives: We sought to investigate the effects of short- and long-term vitamin C therapy on endothelial dysfunction in patients with homocystinuria. Background: Untreated homocystinuria due to cystathionine -synthase deficiency is associated with premature atherothrombotic disease; 25% of untreated patients suffer a vascular event by the age of 16 years and 50% by 29 years. Treatment directed at reducing homocysteine accumulation significantly reduces this risk. However, despite optimal treatment and compliance, hyperhomocysteinaemia usually persists and individuals exhibit endothelial dysfunction indicative of an adverse cardiovascular prognosis. Additional intervention is therefore required to further reduce cardiovascular risk. Methods: We investigated the endothelial effects of acute (2 g single dose) and chronic (1 g/day for 6 months) administration of oral vitamin C in 5 patients with homocystinuria (mean age 26 years, 1 male) and 5 age- and sex-matched controls. Brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent responses to nitroglycerin (NTG) were measured using high-resolution ultrasonic vessel wall-tracking. Results: Baseline: Plasma total homocysteine was 100.8 ± 61.6 and 9.2 ± 1.9 mol/L in the patient and control groups, respectively (p < 0.001). FMD responses were impaired in the patient group (20 ± 40 m) compared with the controls (116 ± 30 m) (p < 0.001). Vitamin C administration: FMD responses in the patient group improved both acutely, 160 ± 65 m at 4 h (p < 0.001), and chronically, 170 ± 70 m at 2 weeks (p < 0.001) and 170 ± 40 m at 6 months (p < 0.001). FMD responses in the control group were unaltered (p = 0.526). Within both groups, neither the vascular response to NTG nor plasma homocysteine was altered (p > 0.4). Conclusions: Vitamin C ameliorates endothelial dysfunction in patients with homocystinuria, independent of changes in homocysteine concentration and should therefore be considered as an additional adjunct to therapy to reduce the potential long-term risk of atherothrombotic disease.     

Automatic CPAP Performance in Patients with Sleep Apnea Plus COPD

Abstract

Background: Automatic CPAP devices have demonstrated good results in obtaining optimal fixed CPAP pressure to eliminate respiratory events in patients with sleep apnea-hypopnea syndrome (SAHS). However, automatic CPAP has not been fully studied in patients with COPD plus SAHS. Objectives: To analyse the performance of an automatic CPAP in severe COPD patients compared with SAHS patients with no associated co-morbidity. Methods: We compared 10 consecutive patients with SAHS and no associated co-morbidity and 10 patients with SAHS plus severe COPD who required CPAP titration. Automatic CPAP performance was studied during full-night PSG. Inadequate pressure increase periods, absence of pressure increases in reaction to respiratory events, air leak periods, and pressure behaviour in the face of erratic breathing periods were analysed. Results: The SAHS patients without co-morbidities vs. SAHS plus COPD patients presented: mean sleep efficiency, 80.2 (11.5)% vs. 76.5 (12.1)%; residual AHI, 6.3 (5.2) vs. 5.1 (7.7); residual CT90, 1 (3)% vs. 14 (1)%. The device´s performance demonstrates a mean of 1.2 (1.5) vs. 1.3 (1.2) periods of inadequate pressure increases; absence of pressure increases in reaction to respiratory events, 4.1 (5.4) vs. 0.6 (0.7) times; periods of air leaks, 1.3 (3.8) vs. 13.9 (11.7); mean optimal pressure, 9.1 (1.4) vs. 9.0 (1.9) cm H₂O. Conclusion: Titration with automatic CPAP could be as effective in patients with SAHS plus severe COPD as in patients with SAHS without COPD. However, the presence of more leakages must be taken into account.     

The effect of short-term dietary supplementation with glucose on gastric emptying of glucose and fructose and oral glucose tolerance in normal subjects

Summary Recent observations indicate that gastric emptying may be influenced by patterns of previous nutrient intake. The aims of this study were to determine the effects of a high glucose diet on gastric emptying of glucose and fructose, and the impact of any changes in gastric emptying on plasma concentrations of glucose, insulin and gastric inhibitory polypeptide in response to glucose and fructose loads. Gastric emptying of glucose and fructose (both 75 g dissolved in 350 ml water) were measured in seven normal volunteers on separate days while each was on a standard diet and an identical diet supplemented with 440 g/day of glucose for 4–7 days. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide levels were taken immediately before and for 180 min after ingestion of glucose and fructose loads. Dietary glucose supplementation accelerated gastric emptying of glucose (50% emptying time 82±8 vs 106±10 min, p=0.004) and fructose (73±9 vs 106±9 min, p=0.001). After ingestion of glucose, plasma concentrations of insulin (p<0.05) and gastric inhibitory polypeptide (p<0.05) were higher during the glucose-supplemented diet. In contrast, plasma glucose concentrations at 60 min and 75 min were lower (p<0.05) on the glucose-supplemented diet. We conclude that short-term supplementation of the diet with glucose accelerates gastric emptying of glucose and fructose, presumably as a result of reduced feedback inhibition of gastric emptying from small intestinal luminal receptors. More rapid gastric emptying of glucose has a significant impact on glucose tolerance.Abbreviations GIP Gastric inhibitory polypeptide - T50 50% gastric emptying time     

Comparison of conventional nighttime with automatic or manual daytime CPAP titration in unselected sleep apnea patients: study of the usefulness of daytime titration studies

Daytime CPAP titration studies with full polysomnography have been successfully performed in patients with severe sleep apnea-hypopnea syndrome (SAHS). The implementation of daytime studies in unselected SAHS patients could help to reduce the waiting lists for CPAP titrations. The main purpose of this study was to compare the effectiveness of conventional versus manual or automatic daytime CPAP titration in unselected patients with SAHS. Ninety-three consecutive patients with SAHS in whom CPAP was indicated were assigned to conventional titration or to manual or automatic (AutoSet) daytime CPAP titration, after sleep deprivation. The number of valid studies, sleep architecture, final pressure selected and mean pressure in the different sleep stages were compared. Changes in sleepiness (Epworth sleepiness score) and hours of CPAP use were assessed after 3 months of treatment. Four patients did not sleep (3 AutoSet, 1 conventional daytime groups). Sleep latency was shorter during automatic daytime titration whereas REM latency was shorter in daytime studies; the percentage of sleep stages was similar during all types of titration. CPAP requirements were significantly higher during REM sleep in conventional and manual daytime titrations while mean pressure was unchanged throughout sleep stages during AutoSet titration. CPAP pressure selected with conventional or daytime manual titration (7.5(2.2) cm H2O and 7.4(1.5) cm H2O, ns) were significantly lower (P< 0.001) than with AutoSet (9.4(1.6) cm H20. All groups showed similar decrease of sleepiness and hours of use of CPAP at 3 months of follow-up. Automatic and manual daytime PSG studies after sleep deprivation are useful for CPAP titration in unselected patients with SAHS. Pressure selected with AutoSet is significantly higher than with conventional daytime or nighttime titration, although not significant in terms of treatment compliance and symptom improvement.     

Adipocyte insulin binding and insulin sensitivity in ‘brittle’ diabetes

Summary Adipocyte insulin binding and insulin sensitivity to stimulation of lipogenesis were assessed in a group of extremely brittle diabetic patients who were resistant to subcutaneous insulin therapy and had required frequent and prolonged hospital admission. These patients had significantly lower maximum adipocyte insulin binding (1.78±0.18%) than age-, sex- and weight-matched stable diabetic control subjects (2.57±0.36%; p<0.05). Scatchard analysis suggested that the decreased binding was secondary to reduced receptor affinity with no change in receptor number. Adipocytes from the brittle subjects displayed resistance to insulin stimulation of lipogenesis compared with those from diabetic or normal control groups (half-maximal stimulation at 34±4, 15±3 and 13±2 pmol/l respectively; p<0.01 between brittle and stable diabetic groups). In the one subject who was treated with intraperitoneal insulin, the changes in insulin binding and sensitivity were found to have reverted towards normal. The peripheral tissue abnormalities of brittle diabetes may exacerbate the clinical syndrome although the relationship of these changes to the primary cause of the syndrome is uncertain.     

The Turkish version of the Bath Ankylosing Spondylitis Functional Index: reliability and validity

The purpose of this study was to investigate the reliability and validity of the Turkish version of the Bath Ankylosing Spondylitis (AS) Functional Index (BASFI). The Turkish version of the BASFI was obtained after a process of translation and back-translation. Eighty-one consecutive patients meeting the 1984 New York criteria for AS were enrolled. Patients were evaluated and requested to complete the questionnaire at days 1 and 2 and on a third occasion between days 15–90. Reliability, reproducibility, validity and sensitivity to change of the Turkish version of the index were assessed. Each score correlated closely with the index score, with coefficients between 0.727 and 0.844. Reliability analysis showed a Cronbachs alpha score of 0.926. Correlations were found between all items of the BASFI and Schobers test (r=–0.258 to –0.531, p<0.001–0.05), occiput-to-wall distance (r=0.284 and 0.589, p<0.001–0.05), and finger-to-floor distance (r=0.334 to 0.613, p<0.001–0.01). The total index score was correlated with the number of nocturnal awakenings (r=0.515, p<0.001), Schobers test (r=–0.444, p<0.001), finger-to-floor distance (r=0.567, p<0.001), occiput-to-wall distance (r=0.535, p<0.001), chest expansion (r=–0.403, p<0.001), and the Dougados articular index (r=0.371, p<0.01). A good correlation was found between day 0 and 1 BASFI indices (r=0.765–0.917, p<0.001), showing good reproducibility of the index. The Turkish version of the BASFI showed reliability, reproducibility, and validity, confirming its utility in the research of AS in Turkey. However, sensitivity to changes due to drug therapy and/or rehabilitation remains to be determined.     

The effect of hand osteoarthritis on grip and pinch strength and hand function in postmenopausal women

The aim of the study was to investigate the effect of osteoarthritis on hand function in postmenopausal women. One hundred patients with hand OA and 70 healthy volunteers as controls were evaluated. Grip and pinch strength measurements and Dreisers functional index were used for hand function. Pain was assessed by a visual analog scale, and tenderness was assessed by palpation and scored, depending on the severity of tenderness, as 0, 1 or 2. Heberdens and Bouchards nodules and joint involvement were also recorded. The number of patients with only distal interphalangeal joint involvement was 50 (50%), those with distal interphalangeal joint plus proximal interphalangeal joint involvement was 49 (49%), and those with carpometacarpal joint involvement numbered 18 (18%). The incidence of Heberdens and Bouchards nodules was 85% and 36%, respectively. Eighty-six (86%) patients were suffering from pain and 57 were found to have tenderness. Grip and pinch strength was significantly lower (p<0.05) and Dreisers functional index score was significantly higher (p<0.001) in the study group (particularly in grade 4 OA). Grip strength was lower in hand OA patients with distal interphalangeal joint plus proximal interphalangeal joint involvement than in those with only distal interphalangeal joint and carpometacarpal joint involvement. Pinch strength was also lower in patients with distal interphalangeal joint plus proximal interphalangeal joint plus carpometacarpal joint involvement. The patients with Heberdens and Bouchards nodules had lower grip and pinch strength than controls. Also, pain and tenderness had significant (p<0.05) effects on hand function. Dreisers total score ranged from 0 to 10 in 80 (80%) patients and from 11 to 20 in 20 patients. In conclusion, hand osteoarthritis contributes to hand dysfunction, mainly related to the severity of osteoarthritis, pain, joint involvement and the presence of nodules.Abbreviations CMC Carpometacarpal - DIP Distal interphalangeal - OA Osteoarthritis - PIP Proximal interphalangeal     

Prospective evaluation of an oral appliance in the treatment of obstructive sleep apnea syndrome

The purpose of this study was to investigate the effects of an oral appliance (OA), with and without mandible advance, in the treatment of obstructive sleep apnea syndrome (OSA). Twenty-four patients diagnosed with OSA agreed to participate in this study. The patients were treated for 3 months (with a removable soft elastic silicone positioner customized with thermoplastic silicone and with a 5-mm opening). Patients were selected, using a randomized design, to receive an OA model either with (12 patients) or without advance (12 patients). Before treatment, a snoring questionnaire, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Functional Outcomes of Sleep Questionnaire (FOSQ), the Epworth Sleepiness Scale (ESS), and polysomnography were completed. Fifteen subjects completed the protocol (13 men, two women). With respect to basal values, the mandible-advanced OA group presented a decrease in the mean apnea–hypopnea index (AHI) (33.8±4.7 versus 9.6±2.1; p<0.01), number of arousals per hour (33.8±13.9 versus 16.0±1.5; p<0.05), ESS score (14.7±5.1 versus 5.1±1.9; p<0.05), snoring score (15.4±1.9 versus 10.1±3.2; p<0.05), and total FOSQ score (78.1±22.6 versus 99.3±14.4; p<0.05). After treatment, the non-advanced group presented a decrease in the mean AHI (24.0±12.2 versus. 11.7±7.9; p<0.05). However, no significant differences were found in the number of arousals per hour, ESS score, snoring, and total FOSQ score in the non-advanced group. Neither study group showed significant difference in mean SF36 scores. Oral appliances, especially those that advance the mandible, offer an effective treatment for OSA.     

Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome

Aims/hypothesis Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction.Methods In 43 healthy control subjects (age 48.2±1.0 years, mean±SEM) and in 48 untreated age-matched subjects with metabolic syndrome (National Cholesterol Education Programs Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique).Results Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1±2.6 vs 43.8±2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r=0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=–0.44, p<0.001), which was impaired in the metabolic syndrome.Conclusions/interpretation These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.     

Outcome of late-onset rheumatoid arthritis

The objective of this study was to determine possible differences in the outcome of patients with rheumatoid arthritis (RA) with disease onset early and late in life. As part of a broader outcome study of RA which included patients seen in the division of Rheumatology of Hospital Universitario Marqués de Valdecilla of Santander, Cantabria (Northern Spain) with disease duration between 2 and 7 years, we selected patients with an age at disease onset of 45 or 65 years. The medical records of all eligible patients were reviewed for relevant clinical and laboratory variables; the patients were then further evaluated for disease activity using biological tests and joint indices such as joint counts and Thompsons Index, functional capacity using the American College of Rheumatology (ACR) functional classification (ACR-FC) and the modified Health Assessment Questionnaire (M-HAQ), and anatomical damage using the number of joint damage (NJD) and radiographs read by the Sharps scoring method for joint erosion (JE), joint narrowing (JN), and overall. Patients in both subsets were then compared. For the multivariable analyses all patients in the original larger cohort were included, so that age could be used as a continuous variable and the power of the analyses could increase; 31 younger (mean age±SD: 36±7 years) and 35 older (73±6 years) patients were available for assessment. No differences in disease duration and gender distribution were observed. Likewise, both subsets had similar levels of disease activity, both articular indices, and biological markers. In contrast, elderly patients showed more functional limitations as per the M-HAQ [median (interquartile range): 0.4 (0.13–1.2) vs 0.13 (0–0.6), p=0.007] and greater anatomical damage as per the NJD [median (interquartile range): 2 (0–4) and 0 (0–2), respectively, p=0.04] and the JE, JN, and total Sharp Index score (p=0.001, 0.02, and 0.001, respectively). Although older patients took fewer disease-modifying antirheumatic drugs (DMARD) and combined DMARD treatments (2.5±1.4 vs 1.9±1.3, p=0.05 and 0.8±1.1 vs 0.3±0.6, p=0.01, respectively), multivariable analysis demonstrated an independent association between age at disease onset and the number of DMARD and functional and anatomical decline. Late-onset RA does not present a better prognosis than the early-onset form of the disease. At the very least the disease is comparable between both patient groups. However, disease compounded by age-associated factors may in fact have a worse prognosis late than early in life.     

Efficacy of mizoribine treatment in patients with SjÖgren’s syndrome: an open pilot trial

The aim of this study was to evaluate the efficacy and safety of mizoribine in patients with SjÖgrens syndrome. Forty patients with sicca syndrome, whose conditions were definitely diagnosed as SjÖgrens syndrome, were given mizoribine orally at a dosage of 150mg/day for 12 months. The percentage change in salivary secretion after 3, 6, and 12 months of the therapy increased to +112.2% (P 0.001), +119.9% (P 0.01), and +147.3% (P 0.001), respectively, compared with the baseline. Serum IgG levels decreased significantly throughout the study, and the level was 1969.4 ± 620.0mg/dl after treatment for 12 months compared with the pretreatment value of 2094.3 ± 746.6mg/dl (P 0.05). The patients assessment of clinical signs and symptoms on a 10-cm visual analog scale improved significantly from 7.2 ± 2.3cm at the start of the treatment to 5.0 ± 1.9cm after 12 months (P 0.001). There was a similar improvement in the physicians assessment using the 10-cm visual analog scale: 7.1 ± 1.6cm at the start of the treatment and 5.2 ± 1.9cm after 12 months (P 0.001). With regard to safety, no serious adverse reactions were observed. Although a controlled study would be required to clarify the efficacy of mizoribine, these preliminary observations indicate its efficacy for ameliorating glandular symptoms through improvements in immune abnormalities in patients with SjÖgrens syndrome.     

Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis

The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3±2.4 µmol/l in group I and 7.87±3.2 µmol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3±15.9 ng/ml and 8.41±2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid.This revised version was published in February 2005 with corrections to the authors affiliations and the abstract.