Serum klotho concentrations inversely correlate with the severity of nailfold capillaroscopic patterns in patients with systemic sclerosis.

Klotho is a transmembrane and soluble glycoprotein that governs vascular integrity. Previous studies have demonstrated reduced serum klotho concentrations in patients with systemic sclerosis (SSc), and it is known that klotho deficiency can impair the healing of digital ulcers related to microvessel damage. The aim of this study was to evaluate the association between serum klotho levels and nailfold capillaroscopic abnormalities in SSc patients. We retrospectively enrolled 54 consecutive patients with SSc diagnosed on the basis of the 2013 EULAR/ACR criteria [11 with diffuse SSc; 47 females; median age 68.0 years (IQ 18); median disease duration 11.0 years (IQ 7)]. Serum klotho concentrations were determined by means of an enzyme-linked immunosorbent assay. On the basis of the 2000 classification of Cutolo et al., 14 patients had normal nailfold capillaroscopic findings, 8 had an early scleroderma pattern, 21 an active scleroderma pattern, and 11 a late scleroderma pattern. The median serum klotho concentration was 0.29 ng/mL (IQ 1). Regression analysis of variation showed an inverse correlation between serum klotho concentrations and the severity of the capillaroscopic pattern (p=0.02; t -2.2284), which was not influenced by concomitant treatment. Logistic regression did not reveal any significant association between the risk of developing digital ulcers and nailfold capillaroscopic patterns, serum klotho levels, or concomitant medications. The presence of avascular areas significantly correlated with calcinosis (p=0.006). In line with previous studies, our findings confirm that klotho plays a role in preventing microvascular damage detected with nailfold capillaroscopy.

Efficacy and safety of anti-TNF agents in the Lombardy rheumatoid arthritis network (LORHEN).

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damages, which consist of joint destruction. Clinical trials have shown that anti-tumour necrosis factor (TNF) drugs are effective in patients with rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs). At about the same time as the European approval of the third anti-TNF agent for treating rheumatoid arthritis (RA) patients, the Italian Society of Rheumatology (Società Italiana di Reumatologia [SIR]) started a database for the registration and active follow-up of patients with RA treated with biological response modifiers. Since 1999, all patients with RA (ACR criteria) and treated with at least one dose of an anti-TNF agent at four Rheumatology Centres in Lombardy (northwest Italy) have been included in the Lombardy Rheumatology Network (LORHEN) registry in order to track the efficacy and safety of the three available TNF inhibitors during the first three years of treatment.

Infliximab-induced lupus in Crohn's disease: a case report.

An 18-year-old male patient was under treatment with infliximab at a dose of 5 mg/kg at Weeks 0, 2 and 6 for refractory Crohn's disease. In June 2002, the patient was admitted to the Outpatient Clinic of the Rheumatology Unit for arthralgia affecting the small joints, non-pruritic crops of purple skin lesions and malar rash in the face. Serum antinuclear antibodies were positive (1:640 speckled pattern), and anti-double-stranded DNA was positive (1:80); moreover, positivity of anti-extractable nuclear antigen was observed. Antihistone antibodies, lupus anticoagulant and anticardiolipin antibodies were negative. A diagnosis of infliximab-induced lupus was made and the drug treatment was withdrawn. However, 3 months after withdrawal of treatment, the patient still showed clinical and laboratory symptoms of systemic lupus erythematosus. After 6 months of treatment, systemic lupus erythematosus-related symptoms disappeared and anti-double-stranded DNA returned to normal. The patient is currently under treatment with prednisone 20 mg/day for systemic lupus erythematosus and with oral mesalazine 2.4 mg/day for Crohn's disease. Treatment with infliximab is known to produce an increase of autoantibodies (antinuclear antibodies, anti-double-stranded DNA), but not clinical disease. This is the first case, to our knowledge, of onset of prolonged infliximab-induced lupus.

Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of oral chicken type II collagen (CII) in the treatment of rheumatoid arthritis (RA). METHODS: Sixty patients with clinically active RA of long duration (mean 7.2 +/- 5.5 years) were treated for 6 months with oral chicken CII at 0.25 mg/day (n = 31) or with placebo (n = 29) in a double-blind randomized study. RESULTS: The response rate to treatment of the collagen-treated group, based on the ACR 20% criteria, was higher than that of the control group but this difference was not statistically significant at any time. Intention-to-treat (ITT) analysis did not show statistically significant improvement in any of the several secondary outcome measures over the 6 months of the study in the collagen-treated patients in comparison with the placebo-treated group. However, in 2 collagen-treated patients we observed a clinical remission according to the criteria of the American Rheumatism Association. CONCLUSION: Our study seems to show that the oral treatment of RA patients with chicken CII is ineffective and results in only small and inconsistent benefits. Furthermore, our results raise the possibility that in a sub-group of patients oral collagen administration, usually considered devoid of harmful effects, may actually induce disease flares.

Prevalence and clinical feature of the "overlap syndrome", obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), in OSA population.

PURPOSE: The association of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), defined overlap syndrome by Flenley, is frequent. Aims of the present study were to assess the frequency of overlap syndrome in 168 consecutive OSA patients, and to evaluate the functional pulmonary hemodynamic, and polysomnographic consequences of this association by comparing Overlap patients with OSA patients. METHODS: From the results of the pulmonary and polysomnographic investigation, patients were classified as OSA patients (group 1), having an apneas/hypopneas index (AH/I) > 15/hr, and Overlap patients (group 2), i. e. OSA patients with an obstructive spirographic pattern (FEV1<60%, FEV1/FVC<65%, RV>130%, RV/TLC>140% of predicted value) not reversible after beta2 agonist inhalation. Group 1 consisted of 135 Patients (115 males, 20 females, age 56+/-10 yr, BMI 32+/-6 Kg/m(2)); the group 2 included 33 patients (30 males, 3 females, age 56+/-11 yr., BMI 34 +/- 6 Kg/m(2)). RESULTS: The OSA and Overlap patients were similar in most respects: age, BMI, clinical characteristic. In awake Overlap patients had lower PaO(2), higher PaCO(2) and Ppa (p<0.001), and an obstructive spirographic pattern, as compared to OSA patients. During sleep the overlap group had a higher AH/I and a lower mean SaO(2) (p<0.05), a reduction of the sleep efficency (p<0.05), and a reduction in the duration of 1NREM and REM sleep stage (p<0.05), as compared to group 1. CONCLUSION: In conclusion, an associated COPD is observed in more than 19% of OSA patients. Overlap patients are at increased risk of developing pulmonary hypertension and show a poorer quality of sleep as compared with OSA patients. The possibility of developing cor pulmonale should be given particular attention in the diagnosis and follow-up of Overlap patients.

Placebo effect and adaptation to noninvasive monitoring of BP.

Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives (mean age 38 +/- 10 yrs, 13 males and 9 females). After the first baseline monitoring, the patients were randomised, according to a cross-over design, to one of the following sequences: no therapy to placebo or placebo to no therapy. At the end of each period, noninvasive ambulatory monitoring was performed. Mean +/- SE 24 h systolic (SBP) and diastolic (DBP) pressures recorded at the first monitoring were 129.2 +/- 3.5 mmHg and 81.7 +/- 2.3 mmHg respectively. At the second and third monitorings, mean 24 h BP differences versus baseline levels were -2.9 +/- 1.8 and -4.7 +/- 1.7 mmHg for SBP, and -2.0 +/- 1.1 and -2.7 +/- 1.5 mmHg for DBP. Both SBP and DBP differences at repeated monitorings were significant by analysis of variance (P less than 0.05). No significant effects on BP of treatment sequence or of placebo administration were found. Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences (SBP: beta = -0.260, DBP: beta = -0.124). ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours. Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of 'white coat'-induced BP increase only for DBP (P = 0.022). For both 24 h SBP and DBP, however, a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed. It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect. Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different.

Slow-release metoprolol and nifedipine in essential hypertension: 24 hour noninvasive ambulatory blood pressure monitoring.

To assess the efficacy and tolerability of metoprolol (MET), 200 mg slow release (SR) q.d., and nifedipine (NIF), 20 mg SR b.i.d., 20 mildly to moderately hypertensive outpatients (14 men and 6 women; mean age 41.5 years, range 27-49 years) were studied. After being withdrawn from previous antihypertensive treatments, the patients were given single-blind placebo for 2 weeks and thereafter, in double-blind, randomized sequence, MET and NIF, both for 2 weeks. At the end of each period of the study, blood pressure (BP) was recorded for 24 h using a noninvasive ambulatory BP monitoring device (ICR System) with readings taken every 10 min (from 6 a.m. to 6 p.m.), 15 min (from 6 to 12 p.m.), and 20 min (from 12 p.m. to 6 a.m.). Five patients did not complete the study because of the occurrence of unwanted effects (one patient on MET and four patients on NIF). In the 15 patients who concluded the study both drugs significantly reduced (p less than 0.01), in comparison with placebo, systolic BP (SBP), mean arterial pressure (MAP), and diastolic BP (DBP) throughout the 24 h (MET: -16.9, -11.5, and -8.9 mm Hg; NIF: -12.7, -8.4, and -6.6 mm Hg, respectively). In comparison with NIF, SBP and MAP but not DBP were significantly reduced by MET (p less than 0.01 and p less than 0.05, respectively). We conclude that in our patient population MET was more effective and better tolerated than NIF. A possible explanation could be the relatively young age of the subjects we studied.

Blood pressure levels in adolescents: the Milan Study.

The relationship between pubertal maturation and blood pressure (BP) was investigated in a cohort of 1,252 adolescents followed for 4 years. Males and females were categorized into two groups (pre and post), according to pubic hair growth (males) and menses onset before or after the age of 12. BP tracking was higher for systolic BP (SBP) than for diastolic BP (DBP), without differences between the two groups of each sex. By multiple regression analysis, initial BP was the major predictor of the final value in all subjects. Body mass index (BMI) annual change was positively correlated to SBP change over time. Analysis of variance showed an increased within-person variability of SBP in pre subjects, with a significant reduction of DBP residual variance at higher initial DBP levels. Our results suggest that early pubertal maturation and high DBP at age 14 years characterize subjects differing at least partially from the general adolescent population in BP determinants.

Ambulatory blood pressure monitoring (24 h), basal blood pressure and left ventricular echocardiographic findings in young adults.

Left ventricular (LV) echocardiography and ambulatory monitoring of blood pressure (BP) were performed in 50 normal 20-year-old subjects previously followed longitudinally for 4 years with annual measurements of basal BP (BBP). The relationship of basal, casual and mean 24-h non-invasive ambulatory BP (ABP) with echo findings, blood chemistries and body fatness was evaluated. Subjects with mean BBP on the 4 years above the 85th percentile showed significantly higher blood levels of urea and glucose and of body fat than subjects below this BP level. Left ventricular echo measurements did not differ in the two groups. Left ventricular diameters and volumes were not correlated with basal, casual or ambulatory BP. Interventricular septum (IVS), LV posterior wall (LVPW) and LV mass were correlated with ambulatory systolic but not with basal or casual BP. A significant increase of wall thickness and LV mass was associated with a mean 24-h ambulatory systolic BP (ASBP) above 129 mmHg. It is concluded that random BP and ABP tend to identify hypertensive subjects with different features.