Primary Sjögren's syndrome: Extraglandular manifestations and hydroxychloroquine therapy.

The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi2 test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.

Perfil lipídico e inflamación en pacientes con artritis reumatoidea: una contradicción? / Lipid profile and inflammatory state in patients with rheumatoid arthritis

INTRODUCCIÓN: Los pacientes con artritis reumatoidea (AR) presentan una mobimortalidad cardiovascular (CV) 50-60% más alta comparada con la población general. En este grupo poblacional, la carga inflamatoria acumulada, medida por los niveles de VSG y PCR durante un período prolongado, se ha asociado con aterosclerosis subclínica, riesgo cardiovascular y mortalidad. En contrapartida, la presencia de un estado pro-inflamatorio conduciría a una disminución del colesterol total (CT), colesterol HDL y colesterol LDL, por lo que la contribución de los lípidos como factor de riesgo CV es, ciertamente, contradictorio. OBJETIVO Correlacionar los reactantes de fase aguda (VSG-PCR) y los valores de lípidos (CT, HDL, LDL) en una muestra de pacientes con AR. PACIENTES Y METODO: Estudio observacional, retrospectivo, analítico, en el que se incluyeron pacientes con diagnóstico de AR según criterios ACR/EULAR 2010. La relación entre los valores de CT, HDL, LDL con la PCR y VSG se analizó con correlación de Pearson. Dada la distribución no simétrica de los valores de PCR, se obtuvo una transformación logarítmica (logaritmo normal) de la misma. En un segundo modelo, los valores de CT, HDL y LDL se correlacionaron con el logaritmo normal de la PCR realizando distintos cortes de la misma (concentración de PCR ≤5 mg/l, > 5 a 10 mg/l). Finalmente, las correlaciones significativas, se incluyeron en un modelo de regresión lineal multivariado ajustado por edad, género, tiempo de evolución de la enfermedad, uso de hipolipemiantes, medicamentos biológicos y dosis de glucocorticoides. RESULTADOS El análisis de este estudio incluyó 449 mediciones del perfil de lípidos y reactantes de fase aguda (PCR y VSG) correspondientes a 318 pacientes. Los pacientes fueron predominantemente mujeres (79.5%), con una edad media (desviación estándar) de 57.7 (12.3) años. La mediana (rango intercuartilo) del tiempo de evolución de la enfermedad fue de 74.0 (108.0) meses. La mayoría de los pacientes eran seropositivos (67%). La correlación entre PCR y CT (r= 0.16; p= 0.60), así como sus fracciones HDL (0.09; p= 0.30) y LDL (r= 0.09; p= 0.36), fueron débiles. En el sub-análisis de la PCR dividida en tres valores de corte, tanto el CT (r= -0.18 a 0.09) y la fracción LDL (r= -0.34 a 0.11) mostraron correlaciones débiles, independientemente del valor de corte analizado de PCR. Por el contrario, se observó una correlación positiva moderada entre los valores positivos intermedios de PCR y HDL (r= 0.53; p= 0.01). Las correlación entre VSG y CT (r=- 0.03; p= 0.58), así como su fracción LDL (r= 0.10; p= 0.88), fueron débiles. Se observó una correlación negativa débil, pero estadísticamente significativa entre VSG y la fracción HDL (r=-0.14; p= 0.02). En el análisis multivariado de regresión lineal la VSG mantuvo una asociación negativa y significativa con los valores de colesterol HDL (coeficiente ß= -0.179, IC95% -0.28 -0.07; p= 0.001). CONCLUSION: En este estudio pudimos corroborar una relación inversa, aunque débil, entre la VSG y la fracción HDLcolesterol, por el contrario, no pudimos reproducir los hallazgos previamente publicados sobre la relación inversa entre la PCR y los niveles séricos de colesterol y sus fracciones. (AU)

INTRODUCTION: Cardiovascular disease (CVD) is the main cause of premature mortality in patients with rheumatoid arthritis (RA). The risk of CVD mortality is increased by approximately 50% compared to the general population. In patients with RA, the cumulative inflammatory burden, as measured by the levels of the globular sedimentation rate (GSR) and the Creactive protein (CRP), has been associated with sub-clinical atherosclerosis, CV risk and mortality. On the contrary, the presence of a proinflammatory state, as observed in patients with RA, may lead to a decline of the total cholesterol (TC) and HDL fraction. This observation suggests that inflammation may play a confounding role in the association of lipids with CVD. OBJETIVO: To correlate acute phase reactants (GSR and CRP) with the lipid measurements (TC, HDL and LDL) in a sample of patients with RA. PATIENTS Y METHOD: In this observational, retrospective and analytic study, we included 318 patients fulfilling the CR/EULAR 2010 criteria for RA. The relationship between the TC, HDL, LDL and the CRP (normal logarithm) and GSR was analyzed with the Pearson´s correlation. In a second model, the relationship of the TC, HDL and LDL with the normal logarithm of CRP was analyzed using different cutoff values (CRP ≤5 mg/l, > 5 a <10 mg/l y >10 mg/l). Finally, all the significant correlations were included in a multivariate linear regression model adjusting for age, gender, disease duration, use of lipid lowering drugs, biologic disease modifying antirheumatic drugs and glucocorticoid doses. RESULTS: The study included 449 measurements of the lipid profile and acute phase reactants. Patients were predominantly women (79.5%) with mean (SD) age of 57.7 (12.3) years. Median (IQR) disease duration was 74.0 (108.0) months. Most of the patients (67%) were either positive for the rheumatoid factor and/or anti-citrullinated antibodies. The correlation of the CRP and TC (r= 0.16; p= 0.6) and their fractions HDL (0.09; p= 0.30) and LDL (r= 0.09; p= 0.36) were positive and weak. In the sub-analyses using the three cut-off values of the CRP, the correlations of both, TC (r= -0.18 to 0.09) and LDL (r= -0.34 to 0.11) were also weak. On the contrary, the correlation between the intermediate values of CRP and HDL was positive and moderate (r= 0.53; p= 0.01). The correlation of the GSR and TC (r=-0.03; p= 0.58) and LDL (r= 0.10; p= 0.88) were weak. There was, however, a negative and significant, although weak correlation between the GSR and HDL (r=-0.14; p= 0.02). In the multivariate analyses, the GSR had a negative and significant association with the levels of HDL (ß coefficient = -0.179, 95%CI - 0.28 -0.07; p= 0.001). CONCLUSION: In this study we confirmed an inverse, although weak, relationship between the GSR and HDL-cholesterol. On the contrary, we were not able to reproduce previous published data regarding the inverse relationship between the CRP values and the levels of the TC or their fractions. (AU)

Pleuropulmonary involvement in patients with systemic lupus erythematosus from a Latin American inception cohort (GLADEL).

Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses. Results At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10-1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR 3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58; 95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63-3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10-2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.

Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort.

OBJECTIVES: The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus erythematosus (SLE). METHODS: We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis. RESULTS: Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20-0.71). CONCLUSIONS: Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.

Lupus in Latin-American patients: lessons from the GLADEL cohort.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the G: rupo L: atino A: mericano D: e E: studio del L: upus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Tercer reporte de eventos adversos con tratamientos biológicos en Argentina. Informe de registro biobadasar / Thrid report of adverse events with biologics in Argentina. Report from biobadasar registry

Introducción: BIOBADASAR (Registro Argentino de Eventos Adversos con Tratamientos Biológicos en Reumatología) comenzó en agosto de 2010. La importancia de este registro es mostrar datos locales que, probablemente, puedan diferir de otros registros. El objetivo es comunicar los resultados del tercer reporte de BIOBADASAR. Métodos: Todos los pacientes con enfermedades reumáticas que requirieron tratamiento con agentes biológicos y pacientes controles sin estos tratamientos fueron incluidos en la base de datos provenientes de 32 centros participando a lo largo de la Argentina. Tres áreas de datos son analizados: características de los pacientes, tratamientos y eventos adversos...

Introduction: BIOBADASAR (Argentine Registry of Adverse Events with Biological Treatments in Rheumatology) began in August 2010. The importance of this registry is to show local data that may probably differ from other registries. The objective is to communicate the results of the third BIOBADASAR report. Methods: All patients with rheumatic diseases who required treatment with biological agents and control patients without these treatments were included in the database from 32 participating centers throughout Argentina. Three areas of data are analyzed: patient characteristics, treatments and adverse events...

PP100. Pre-eclampsia: Risk factors and outcomes - A two-year study.

INTRODUCTION: Pre-eclampsia (PE) is a hypertensive disorder responsible for major morbidity and mortality in both mother and fetus. There are some risk factors associated with this entity, but it remains very difficult to predict. OBJECTIVES: Study the incidence of PE and the related risk factors, as well as the maternal and fetal outcome. METHODS: We reviewed the clinical records of pregnant women admitted to Prof. Fernando Fonseca's Hospital from January 2008 to December 2009, with the diagnosis of pre-eclampsia. The statistic analysis was based on Excel 2007. RESULTS: There were 90 cases of PE, among the 308 hypertensive disorders reviewed, with an incidence of 1,1% in overall population of pregnant women. Risk factors with higher association were Chronic Hypertension before pregnancy (24,4%), maternal age above 35 years old (16,67%), maternal age under 20 years old (14,44%), and previous episode of pre-eclampsia (8,89%). Major maternal complications that determined Intensive Care Unit admission were recorded in 17 cases (18,89%), with 3 HELLP syndromes (Hemolysis, elevated liver enzymes, and low platelets)(3,33%). No maternal death was recorded. Preterm delivery (PTD) was seen in 61,1%, 32% before 34weeks and 6,67% before 28weeks. There were 19 cases of 1st minute Apgar Index below 7 and 5 cases of 5th minute Apgar Index below 7. There was one in utero death and two interruptions of pregnancy below 24 weeks due to serious PE. Three twin pregnancies. CONCLUSIONS: PE is a form of hypertensive pregnancy disorder, with a risk of recurrence in subsequent pregnancies. It has a catastrophic potential, mainly associated to PTD, and also with significant morbidity to the pregnant women, reflected in the incidence of admissions to ICU, HELLP syndrome and end-organ failure. In our study we confirmed the adverse outcomes related to this entity, and the risk factors associated.

PP151. Hypertensive complications in pregnancy - Two year study (2008-2009).

INTRODUCTION: Hypertension affects 10% of all pregnancies and accounts for approximately a quarter of all antenatal admissions. Hypertension in pregnancy includes a wide spectrum of conditions, including pre-eclampsia, eclampsia, pre-eclampsia superimposed on chronic hypertension, chronic hypertension, and gestational hypertension. Pregnancies complicated by hypertension are associated with increased risk of adverse fetal, neonatal and maternal outcomes, including preterm birth, fetal growth restriction, perinatal death, acute renal or hepatic failure, ante partum haemorrhage, postpartum haemorrhage and maternal death. Overall pre-eclampsia complicates 5-6% of pregnancies and eclampsia complicates 1-2% of pre-eclamptic pregnancies. OBJECTIVES: Analysis of the maternal complications (incidence of ICU admissions, preeclampsia/eclampsia, renal or cardiovascular acute dysfunction, HELLP syndrome, placental abruption, maternal death) and fetal/neonatal outcome. METHODS: In a retrospective study, from January 2008 to December 2009, all files related with complications of hypertensive disorders, seen in our institution, were analysed. The statistic analysis was based on Excel 2007. RESULTS: Of 309 cases, 123 patients (40%) were found to have gestational hypertension while 121 (40%) suffer chronic hypertension. Ninety patients (29%) have preeclampsia or eclampsia (4 cases). 22 patients with chronic hypertension had a superimposed preeclampsia. Fetal growth restriction, HELLP syndrome and placental abruption were the obstetric complications in 4%, 1% and 1% of the cases, respectively. Additionally, multiple pregnancy and gestational diabetes were noted in 2.6% and 10.7% of the patients. Delivery route was vaginal in 90 patients while 68.9% underwent caesarean section. 6.5% of the patients were admitted to ICU and no woman has died. Preterm delivery occurred in 26.2% of the cases and 2 interruptions of pregnancy before 24weeks were performed due to maternal complications. Intrauterine fetal demise was recorded in 2 cases on admission. CONCLUSION: Women with hypertensive disorders of pregnancy are more likely to have received medical or obstetric interventions such as caesarean section operations. Pregnancies complicated by preeclampsia and eclampsia may be associated with life-threatening complications for both the mother and infant.

[Bacterial endocarditis caused by salmonella in systemic lupus erythematosus]. / Endocarditis por salmonella en lupus eritematoso sistemico.

INTRODUCTION: Patients with SLE (Systemic Lupus Erythematosus) are prompt to develop infections with significant morbidity and mortality. The intravascular infection due to salmonella is a rare complication of difficult diagnosis and poor prognostic. OBJECTIVE: We report two cases of bacterial endocarditis due to salmonella in SLE patients. CLINICAL CASES: We report two cases of bacterial endocarditis caused by Salmonella in a patient with SLE, one with recent onset of mellitus diabetes and other with chronic renal failure. Despite of antibiotic treatment with fluoroquinolone and a third-generation cephalosporin, the patient required surgical intervention. CONCLUSION: Salmonella infection should be suspected in SLE patients in order to make earlier diagnosis and treatment.

Treatment of hepatitis C virus infection in kidney transplant recipients: case report.

Chronic hepatitis C virus (HCV) infection exists in a large proportion of patients undergoing renal transplantation. Nowadays it is not considered to be an absolute contraindication to transplantation; however, it is associated with an increased risk for the patient and accounts for a shorter half-life of the renal allograft. We present three transplant recipients who displayed serious hepatic dysfunction after renal transplantation due to an HCV infection. In two of these cases, the liver biopsies established the diagnosis of FCH. In the third case, the liver biopsy was compatible with the early stages of FCH. All patients were started on peg-interferon alfa 2-b and ribavirin with subsequent normalization of hepatic function and early complete viral responses.

Obstructive sleep apnoea syndrome as a cause of road traffic accidents.

UNLABELLED: Several studies have demonstrated that obstructive sleep apnoea syndrome (OSAS) patients have a higher rate of road traffic accidents. Our study aimed to analyse any differences in OSAS patients between those who reported having had road traffic accidents and/or near misses and those who did not. METHODS: We studied 163 patients with OSAS (apnoea- hypopnoea index (AHI)>10/h) diagnosed using nocturnal polysomnography (NPSG), all drivers, 18.4% of whom drove for a living. Patients were asked at their first clinical interview to self-report road traffic accidents and/or near misses over the past 3 years which had been caused by abnormal daytime drowsiness. This allowed patients to be divided into two groups, those who had had road traffic accidents and/or near misses and those who had not. Both were compared as to age, body mass index (BMI), Epworth Sleepiness Scale (ESS), daytime PaO2 and PaCO2, Functional Outcomes of Sleep Questionnaire (FOSQ) test and NPSG data. This latter was total sleep time (TTS), sleep efficiency, sleep stages, arousal index (ARI), AHI, minimal and average SaO2, % of time with SaO2 < 90% (T90), desaturation index (ODI), total duration of apnoea-hypopnoea (TDAH) (T test). RESULTS: Group I (no road traffic accidents) No=89 patients; group II (road traffic accidents) No=74 patients. Age (years) was 57.6+/-11.8 vs. 54.7+/-10.9 (ns); male gender, 75% vs. 78.4%; ESS, 12.3+/-5.4 vs. 17.6+/-4.3 (p<0.001); BMI, (Kg/m2) 36.2+/-8.1 vs. 35.6+/-6.3 (ns); PaO2 (mmHg), 76.1+/-11.4 vs. 78.5+/-12.6 (ns); PaCO2 (mmHg), 42.6+/-5.1 vs. 42.2+/-4.7 (ns); FOSQ, 15.1+/-3.1 vs. 12.9+/-3.4 (p<0.001). NPSG data revealed differences only in AHI: 45.0+/-21.6 vs. 56.2+/-29.7 (p=0.01) and in TDAH (minutes), 98.5+/-63.7 vs. 133.3+/-83.2 (p=0,005). CONCLUSIONS: In our experience patients who had road traffic accidents and/or near misses had a more severe OSAS, with higher AHI, excessive daytime sleepiness and lower quality of life.

Four years' follow up at a smoking cessation clinic.

UNLABELLED: Smoking is an important cause of pulmonary pathology and this addiction can be regarded as a chronic, recurrent disease. The benefits of smoking cessation are unquestionable and all physicians should become more active and assertive in recommending it. AIM: To characterise the population seeking medical support for smoking cessation and understand why some successfully stop smoking and others do not. MATERIAL AND METHODS: Retrospective analysis of medical records of outpatients in follow-up between January 2003 and June 2006. Age, gender, age at smoking initiation, smoking burden (number of pack-years), associated diseases, degree of dependence (Fagerström test for nicotine addiction), prior attempts at and motivation for smoking cessation, need for cognitive/behavioural support and success and abandonment rates were evaluated. RESULTS: Five hundred and twenty six patients were studied, 50% male with an average age of 45.5+/-11.4 years. Almost half (43.1 %; n=227) of the patients started smoking before the age of 15. Average smoking burden was 35.8+/-20 pack-years although 21.4% (n=113) smoked more than 50 pack-years. Respiratory disease was present in 52.1% (COPD, 39.9% and others, 12.2%) and cardiovascular disease in 14.6% of the patients. In 46% of patients (n=242) a relevant psychiatric disorder was identified; depression (21.4%), anxiety disorder (19.4%), other dependencies (2.1%) bipolar disorder (1.5%) and schizophrenia (0.6%). The evaluation of degree of addiction revealed maximum level in 69.7% of the patients (n=380). Many patients (72.2%; n=380) reported prior attempts to quit smoking. The strongest reasons for giving up smoking were concern over health (83.5%), financial issues (8.2%) and search for better quality of life (5.7%). Most patients (81.7%; n=430) had undergone nicotine replacement therapy; skin patches (53.3%), chewing gum (1.1%) or both (45.6%). Psychopharmacological treatment included administration of sedative-hypnotics (86.5%), bupropion hydrochloride (2.3%) and antidepressants (0.6%). Seventy six patients (14%) benefited from cognitive/ behavioural support. Two hundred and twenty three patients (42.4%) were successful in giving up smoking while 219 (41.6%) abandoned follow up, the majority after the first appointment. Most patients that abandoned follow up reported lack of motivation and the price of therapy. CONCLUSIONS: The population under study had a high rate of psychiatric disorders and a high level of dependence and lack of motivation that might justify the drop-out rate. Successful treatment was associated with close follow up, behavioural support and pharmacological therapy.

Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study.

OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.

Lung cavitation in primary antiphospholipid syndrome.

Pulmonary complications of primary antiphospholipid syndrome are common and diverse, with thromboembolic events counting as the most frequent manifestation. We present the case of a female patient with a diagnosis of primary antiphospholipid syndrome, pulmonary thromboembolism and infarction followed by lung cavitation.

Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis.

OBJECTIVE: To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid). METHODS: Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting). RESULTS: Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2% (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs 48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1% vs 9.1% (p=0.029). No significant differences were observed in efficacy. CONCLUSION: Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).

Refinement of the chromosome 5p locus for familial calcium pyrophosphate dihydrate deposition disease.

Familial calcium pyrophosphate dihydrate deposition disease (CPPDD) is a disease of articular cartilage that is radiographically characterized by chondrocalcinosis due to the deposition of calcium-containing crystals in affected joints. We have documented the disease in an Argentinean kindred of northern Italian ancestry and in a French kindred from the Alsace region. Both families presented with a common phenotype including early age at onset and deposition of crystals of calcium pyrophosphate dihydrate in a similar pattern of affected joints. Affected family members were karyotypically normal. Linkage to the short arm of chromosome 5 was observed, consistent with a previous report of linkage of the CPPDD phenotype in a large British kindred to the 5p15 region. However, recombinants in the Argentinean kindred have enabled us to designate a region<1 cM in length between the markers D5S416 and D5S2114 as the CPPDD locus.

In vitro DNA replication by cytoplasmic extracts from cells infected with African swine fever virus.

A cell-free system that catalyzes DNA replication was prepared from cytoplasmic extracts of Vero cells infected with African swine fever virus (ASFV). The cells were permeabilized with lysolecithin and disrupted by mild mechanical action and the nuclei were removed by low-speed centrifugation. Extracts prepared from infected cells at the time of maximal DNA replication incorporated [alpha-32P]dTTP into acid-insoluble material that was sensitive to DNase and resistant to RNase. The reaction was inhibited by phosphonoacetic acid, an inhibitor of ASFV-specific DNA polymerase. Extracts from mock-infected cells had a negligible activity. Micrococcal nuclease-treated extracts were able to replicate added virion DNA or viral replicative DNA. An increase in the mass of DNA detected by ethidium bromide staining and by dot blot hybridization with ASFV DNA showed that the incorporation was due to true replication. Plasmid DNA was also replicated, which indicates that ASFV-specific DNA polymerase does not require a virus-specific origin of replication. The pattern of fragments generated by EcoRI digestion of the in vitro product was characteristic of viral replicative DNA. Hybridization with a recombinant plasmid containing a terminal fragment of ASFV DNA confirmed the presence of dimer terminal ASFV fragments presumably generated from concatemeric replicative intermediates.

Leprosy in Portugal 1946-80: epidemiologic patterns observed during declining incidence rates.

Compulsory notification of leprosy in Portugal formed the basis for the establishment of a national patient registry used in an epidemiological study. Highest incidence rates were observed in the coastal counties in the middle of Portugal and particularly in the municipalities with a high annual rainfall. Peak incidence rates in males was observed at the age of 25-29 years against 50-59 in females. A continuous and increasing decline in incidence rates was observed throughout the observation period, 1946-80. Towards the end of the period the slopes of the incidence curves seemed to be identical with those observed in other countries where leprosy has previously been eradicated. This is consistent with the notion that towards the end of an endemic situation no new transmission of the disease occurs, and the incidence curve takes the shape of the right part of the distribution of incubation periods which apparently is uniform in leprosy, irrespective of time and place. The pattern observed in other areas during declining incidence rates, of an increase in age at onset by year of onset together with a lack of increase in age at onset by year of birth was confirmed by the Portuguese data, also consistent with a break in the transmission of the disease a long time before the final termination of the endemic situation.

In vitro transcription by cytoplasmic extracts from cells infected with African swine fever virus.

A cell-free system for the study of transcription of African swine fever virus (ASFV) mRNA was developed from cytoplasmic extracts of infected cells permeabilized with lysolecithin. Extracts prepared from infected cells early and late after infection incorporated [alpha-32P]UTP into acid-insoluble material that was resistant to DNase and sensitive to RNase. The incorporation was inhibited by actinomycin D but not by alpha-amanitin. The presence of the nuclei was not required. In vitro transcription was optimal at pH 7.9 and at concentrations of 100 mM NH4Cl, 5 mM magnesium acetate, and 250 microM MnCl2. Early infected cell extracts transcribed from endogenous viral DNA a set of RNAs similar in electrophoretic migration to that observed in intact infected cells. Late infected cell extracts seemed to be unable to transcribe new RNA species besides those transcribed early after infection. The activity of the extracts could be made dependent on exogenous templates by digestion with micrococcal nuclease. RNAs transcribed after addition of native or denatured viral DNA to nuclease-treated extracts were indistinguishable from those transcribed from endogenous viral DNA. Late infected cell extracts digested with micrococcal nuclease were also active in transcribing virus-specific RNA from p2SB21, a recombinant plasmid containing the SalI B fragment of ASFV DNA.