Fibromyalgia in primary antiphospholipid (Hughes) syndrome

Fibromyalgia (FM) is a syndrome that can be associated with several rheumatic diseases. However, no study has evaluated its frequency in patients with primary antiphospholipid syndrome (PAPS). The objective of this study was to analyze the frequency of FM in PAPS patients compared with healthy controls, to determine the possible associations between FM and PAPS features, and also to evaluate quality of life and depression in these patients. This case-control study included 30 PAPS patients (by the Sapporo criteria) and 40 healthy subjects. Demographic and clinical data, drug use, and antiphospholipid antibodies were analyzed. FM was diagnosed based on international criteria (ACR). Questionnaires on quality of life, including the Short Form 36 Health Survey (SF-36), Beck Depression Inventory (BDI), Fibromyalgia Impact Questionnaire (FIQ), and Visual Analog Scale (VAS), were also applied. PAPS patients and controls were similar in mean age as well as in distributions of gender and Caucasian race. Mean disease duration was 5.4 +/- 4.2 years. A diagnosis of fibromyalgia was made in five (16.7%) PAPS patients and no controls (p = 0.012). PAPS patients had more diffuse pain (53% vs. 0%, respectively, p<0.0001), >= 11 tender points (23% vs. 5%, respectively, p = 0.032), and a greater total number (175 vs. 57, respectively, p<0.0001) as well as median number of tender points per patient than controls (5 [0-18] vs. 0 [0-11], respectively, p<0.0001). PAPS patients had lower values in all dimensions of the SF-36, as well as higher FIQ scores, higher BDI scores, more depression diagnoses according to BDI results, and increased VAS in comparison with controls. Analysis of PAPS patients with FM compared with those subjects without FM revealed no significant differences regarding demographic features or thrombotic or clinical events; however, PAPS patients who also had FM had lower values in SF-36 dimensions as well as higher FIQ (82.6 +/- 9.6 vs. 33.6 +/- 29.8, respectively, p<0.0001) and VAS scores (6.6 +/- 2.97 vs. 3.25 +/- 3.11, respectively, p = 0.03). BDI scores, in contrast, were similar in both groups. In conclusion, one-fifth of PAPS patients had fibromyalgia and a low quality of life when compared with healthy subjects. Lupus (2011) 20, 1182-1186.

Reaching C-Reactive Protein and Low-Density Lipoprotein Cholesterol Goals in Dyslipidemic Patients (from the Lipid Treatment Assessment Project [L-TAP] 2)

The purpose of the present substudy of the Lipid Treatment Assessment Project 2 was to assess dual C-reactive protein (CRP) and low-density lipoprotein (LDL) cholesterol goal attainment across a spectrum of low-, moderate-, and high-risk patients with dyslipidemia in 8 countries in North America, Latin America, Europe, and Asia. Of the 9,518 patients studied overall, 45% were women, 64% had hypertension, 31% had diabetes, 14% were current smokers, 60% were high risk, and 79% were taking a statin. The median CRP level was 1.5 mg/L (interquartile range 0.2 to 2.8). On multivariate analysis, higher CRP levels were associated with older age, female gender, hypertension, current smoking, greater body mass index, larger waist circumference, LDL cholesterol level, and triglyceride/high-density lipoprotein cholesterol ratio. In contrast, being from Asia or taking a statin was associated with lower levels. Across all risk groups, 59% of patients attained the CRP target of <2 mg/L, and 33% had <1 mg/L. Overall, 44% of patients attained both their National Cholesterol Education Program Adult Treatment Panel III LDL cholesterol target and a CRP level of <2 mg/L, but only 26% attained their LDL cholesterol target and a CRP level of <1 mg/L. In the very high-risk group with coronary heart disease and >= 2 risk factors, only 19% attained both their LDL cholesterol goal and a CRP level of <2 mg/L and 12% their LDL cholesterol goal and a CRP level of <1 mg/L. In conclusion, with current treatment, most dyslipidemic patients do not reach the dual CRP and LDL cholesterol goals. Smoking cessation, weight reduction, and the greater use of more potent statins at higher doses might be able to improve these outcomes. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1639-1643)

Tricho-rhino-phalangeal syndrome: first brazilian case

Thrico-rhino-falangeal syndrome is a rare genetic disease characterized by the presence of typical alterations with a long, bulbous nose, hair alterations, a long flat philtrum, and one-shaped epiphyses of the phalanges. We describe herein the first Brazilian case of a 24-year-old woman with thrico-rhino-falangeal syndrome type I. Physical examination demonstrated typical nose and hair abnormalities, and one-shaped epiphyses of the phalanges, and the genetic study confirmed the diagnosis. Thrico-rhino-falangeal syndrome is characterized by musculoskeletal alterations that at the first view may simulate juvenile idiopathic arthritis. These musculoskeletal deformities could imply the differential diagnosis with rheumatic diseases.

Effects of Perilipin (PLIN) Gene Variation on Metabolic Syndrome Risk and Weight Loss in Obese Children and Adolescents

Context: Genetic polymorphisms at the perilipin (PLIN) locus have been investigated for their potential utility as markers for obesity and metabolic syndrome (MS). We examined in obese children and adolescents (OCA) aged 7-14 yr the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multi-disciplinary behavioral and nutritional treatment without medication. Design: A total of 234 OCA [body mass index (BMI = 30.4 +/- 4.4 kg/m(2); BMI Z-score = 2.31 +/- 0.4) were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1 6209T -> C, PLIN4 11482G -> A, PLIN5 13041A -> G, and PLIN6 14995A -> T). Results: Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in linkage disequilibrium (D` = 0.999; P < 0.001). At baseline, no anthropometric differences were observed, but minor allele A at PLIN4 was associated with higher triglycerides (111 +/- 49 vs. 94 +/- 42 mg/dl; P = 0.003), lower high-density lipoprotein cholesterol (40 +/- 9 vs. 44 +/- 10 mg/dl; P = 0.003) and higher homeostasis model assessment for insulin resistance (4.0 +/- 2.3 vs. 3.5 +/- 2.1; P +/- 0.015). Minor allele A at PLIN4 was associated with MS risk (age and sex adjusted) hazard ratio 2.4 (95% confidence interval = 1.1-4.9) for genotype GA and 3.5 (95% confidence interval = 1.2-9.9) for AA. After intervention, subjects carrying minor allele T at PLIN6 had increased weight loss (3.3 +/- 3.7 vs. 1.9 +/- 3.4 kg; P = 0.002) and increased loss of the BMI Z-score (0.23 +/- 0.18 vs. 0.18 +/- 0.15; P +/- 0.003). Due to group size, risk of by-chance findings cannot be excluded. Conclusion: The minor A allele at PLIN4 was associated with higher risk of MS at baseline, whereas the PLIN6 SNP was associated with better weight loss, suggesting that these polymorphisms may predict outcome strategies based on multidisciplinary treatment for OCA. (J Clin Endocrinol Metab 93: 4933-4940, 2008)

Analysis of the PTPN11 gene in idiopathic short stature children and Noonan syndrome patients

Background Mutations in the PTPN11 gene are the main cause of Noonan syndrome (NS). The presence of some NS features is a frequent finding in children with idiopathic short stature (ISS). These children can represent the milder end of the NS clinical spectrum and PTPN11 is a good candidate for involvement in the pathogenesis of ISS. Objective To evaluate the presence of mutations in PTPN11 in ISS children who presented NS-related signs and in well-characterized NS patients. Patients and methods We studied 50 ISS children who presented at least two NS-associated signs but did not fulfil the criteria for NS diagnosis. Forty-nine NS patients diagnosed by the criteria of van der Burgt et al. were used to assess the adequacy of these criteria to select patients for PTPN11 mutation screening. The coding region of PTPN11 was amplified by polymerase chain reaction (PCR), followed by direct sequencing. Results No mutations or polymorphisms were found in the coding region of the PTPN11 gene in ISS children. Nineteen of the 49 NS patients (39%) presented mutations in PTPN11. No single characteristic enabled us to distinguish between NS patients with or without PTPN11 mutations. Conclusion Considering that no mutations were found in the present cohort with NS-related signs, it is unlikely that mutations would be found in unselected ISS children. The van der Burgt et al. criteria are adequate in attaining NS diagnosis and selecting patients for molecular studies. Mutations in the PTPN11 gene are commonly involved in the pathogenesis of NS but are not a common cause of ISS.

Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare autosomal recessive disorder characterized by permanent neonatal diabetes mellitus, epiphyseal dysplasia, and other multisystemic clinical manifestations. We described two novel mutations in the EIF2AK3 gene in two consanguineous families with WRS from Brazil and Morocco. We have observed in case 1 a homozygous C > T replacement at base pair c.1192 at exon 7, generating a stop codon at position 398 (Gln398Stop). Both of his parents were found to be heterozygous for the mutation. We detected in both parents of case 2, a deceased Moroccan girl, a duplication of base pair c.851A at exon 5 (c.851dupA) leading to a frameshift and a stop codon at position 285 (p.Pro285AlafsX3). Both cases 1 and 2 had neonatal diabetes mellitus, multiple epiphyseal dysplasia, and growth delay, and presented episodes of acute hepatic dysfunction. Case 1 presented central hypothyroidism, developmental delay, and mild mental retardation. Case 2 presented a fatal episode of acute renal failure. The clinical phenotype associated with the syndrome can be variable, but a combination of infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, and hepatic and/or renal dysfunction is the mainstay of diagnosis.

Goodpasture`s syndrome

Goodpasture`s syndrome (GS) is an auto-immune disease that is part of the pulmonary-renal syndrome spectrum. It is characterized by the linear deposition of anti-glomerular basement membrane antibodies (anti-GBM) in glomerular and alveolar basement membrane, resulting in alveolar hemorrhage and progressive glomerulonephritis. An early diagnosis is important to decrease clinical morbidity. In the present work, we illustrate a GS case, initially diagnosed as Wegener`s granulomatosis.The patient showed favorable clinical evolution with corticosteroid therapy associated with plasmapheresis and cyclophosphamide.

Laparoscopic treatment of type 2 diabetes mellitus for patients with a body mass index less than 35

Background Type 2 diabetes mellitus (T2DM) is a common disease with numerous complications. Bariatric surgery is an efficient procedure for controlling T2DM in morbidly obese patients. In T2DM, the incretin effect is either greatly impaired or absent. This study aimed to evaluate the preliminary results from interposing a segment of ileum into the proximal jejunum associated with a sleeve or diverted sleeve gastrectomy to control T2DM in patients with a body mass index (BMI) less than 35 kg/m(2). Methods For this study, 39 patients (16 women and 23 men) underwent two laparoscopic procedures comprising different combinations of ileal interposition into the proximal jejunum via a sleeve or diverted sleeve gastrectomy. The mean age of these patients was 50.3 years (range, 36-66 years). The mean BMI was 30.1 kg/m(2) (range, 23.4-34.9 kg/m(2)). All the patients had a diagnosis of T2DM that had persisted for at least 3 years and evidence of stable treatment with oral hypoglycemic agents or insulin for at least 12 months. The mean duration of T2DM was 9.3 years (range, 3-22 years). Results The mean operative time was 185 min, and the median hospital stay was 4.3 days. Four major complications occurred in the short term (30-days), and the mortality rate was 2.6%. The mean postoperative follow-up period was 7 months (range, 4-16 months), and the mean percentage of weight loss was 22%. The mean postoperative BMI was 24.9 kg/m(2) (range, 18.9-31.7 kg/m2). An adequate glycemic control was achieved for 86.9% of the patients, and 13.1% had important improvement. The patients whose glycemia was not normalized were using a single oral hypoglycemic agent. No patient needed insulin therapy postoperatively. All the patients except experienced normalization of their cholesterol levels. Targeted triglycerides levels were achieved by 71% of the patients, and hypertension was controlled for 95.8%. Conclusions The laparoscopic ileal interposition via either a sleeve gastrectomy or diverted sleeve gastrectomy seems to be a promising procedure for the control of T2DM and the metabolic syndrome. A longer follow-up period is needed.

Influence of gender on the clinical and laboratory spectra of patients with primary antiphospholipid syndrome

The objectives of this cross-sectional study were to evaluate the differences between males and females in the clinical and biochemical manifestations of primary antiphospholipid antibody syndrome (PAPS). The method involved 49 patients (38 premenopausal females and 11 males) diagnosed with PAPS (according to the Sapporo criteria) and their demographic data, clinical data, medications used and antiphospholipid antibodies were analyzed. The results of this study are as follows. Both the groups of patients were statistically similar regarding age, race, weight and body mass index. However, males were significantly taller than females (172 +/- A 8.9 vs. 159.2 +/- A 6.2 cm, p < 0.0001). The duration of disease was similar for females and males. The prevalence of pulmonary thromboembolism was higher in females than in males (34.2 vs. 0.0%, p = 0.024). Regarding other PAPS manifestations (arterial events, venous events, deep venous thrombosis, thrombocytopenia, acute myocardial infarction, angina, cerebrovascular accidents and Sneddon syndrome), comorbidities (arterial hypertension and dyslipidemia), lifestyle (physical activity, previous smoking and current smoking) and the use of medications (current and previous use of corticosteroids, as well as the use of statins or chloroquine), both groups were statistically similar (p > 0.05). More females than males tested positive for IgM anticardiolipin antibodies (76.3 vs. 36.4%, p = 0.025) or for at least one of the antiphospholipid antibodies tested (either IgM anticardiolipin or IgG anticardiolipin 84.2 vs. 45.5%, p = 0.016). However, both groups were similar regarding the frequency of positivity for lupus anticoagulant and isolated IgG anticardiolipin, as well as regarding mean levels of IgG and IgM anticardiolipin (p > 0.05). We concluded that, among PAPS patients, the frequency of pulmonary thromboembolism and of positivity for IgM anticardiolipin is higher in females than in males. Our findings show that there are gender differences in PAPS, differences that might be related to alterations in sex hormones.

Increased Transactivation Associated with SOX3 Polyalanine Tract Deletion in a Patient with Hypopituitarism

Backgound and Aims: Correct gene dosage of SOX3 is critical for the development of the hypothalamo-pituitary axis. Both overdosage of SOX3, as a result of gene duplication, and loss of function resulting from expansion of the first polyalanine (PA) tract are associated with variable degrees of hypopituitarism, with or without mental retardation. The aim of this study was to further investigate the contribution of SOX3 in the etiology of hypopituitarism and the mechanisms involved in the phenotypic variability. Methods: We screened 154 patients with congenital hypopituitarism and an undescended posterior pituitary for mutations in SOX3 and variability in the length of the first PA tract. In addition, 300 patients with variable septooptic dysplasia were screened for variability of the PA tract. Results: We report a novel 18-base pair deletion (p.A243_A248del6, del6PA) in a female patient with hypopituitarism resulting in a 2-fold increase in transcriptional activation in vitro, compared with wild-type SOX3. We also identified a previously reported seven-alanine expansion (p.A240_A241ins7, +7PA) in two male siblings with isolated GH deficiency and a distinct phenotype, in addition to the nonsynonymous variant p.R5Q in an unrelated individual; this appears to have no functional effect on the protein. In contrast to +7PA, del6PA maintained its ability to repress beta-catenin mediated transcription in vitro. Conclusion: This is the first study to report that PA tract deletions associated with hypopituitarism have functional consequences in vitro, possibly due to increased activation of SOX3 target genes. In addition, we have expanded the phenotypic spectrum associated with PA tract expansion (+7PA) mutations to include panhypopituitarism or isolated GH deficiency, with or without mental retardation. (J Clin Endocrinol Metab 96: E685-E690, 2011)

Primary antiphospholipid syndrome with and without Sneddon`s syndrome

The main objective of this study was to compare clinical and laboratory data obtained from patients with primary antiphospholipid syndrome (PAPS) with and without Sneddon`s syndrome (SS). A transverse study with 54 (85.2% female) PAPS patients (Sapporo criteria) was performed. Demographic, drug use, and antiphospholipid antibodies data were evaluated, as well as clinical and laboratory findings of SS. Patients were subdivided into one of two groups: PAPS with SS and PAPS without SS. Both groups were similar with respect to age (p = 0.05), gender (p = 0.34), race (p = 0.31), weight (p = 0.93), height (p = 0.27), and body mass index (p = 0.75); however, the SS group exhibited higher disease duration (96.0 +/- A 54.9 vs. 55.2 +/- A 52.0 months, p = 0.01). By definition, all PAPS with SS patients suffer from stroke, an arterial event; the frequency of stroke events (28.5 vs. 7.5%, p = 0.04), as well as of limb ischemia (100 vs. 30.0%, p < 0.0001) was higher in this group than in the PAPS without SS group. On the other hand, patients in the PAPS without SS group had more venous events, such as deep venous thrombosis, than those in the PAPS with SS group (80.0 vs. 50.0%, p = 0.03). In conclusion, an understanding of the relationship between APS and SS is important in order to identify a subgroup for which more rigorous accompaniment and therapy may be necessary.

Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue

Introduction: Airway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients. Methods: We retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student`s t test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test. Results: Thirty-one ARDS patients (A: PaO(2)/FiO(2) <= 200, 45 +/- 14 years, 16 males) and 11 controls (C:52 +/- 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 +/- 27.2%, C:76.7 +/- 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 +/- 35.2%, C:21.8 +/- 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 +/- 54.3 mu m, C:86.4 +/- 33.3 mu m, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P = 0.03). The extension of normal epithelium showed a positive correlation with PaO(2)/FiO(2) (r(2) = 0.34; P = 0.02) and a negative correlation with plateau pressure (r(2) = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO(2)/FiO(2) (r(2) = 0.27; P = 0.04). Conclusions: Structural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.

Repetitive Transcranial Magnetic Stimulation Is Efficacious as an Add-On to Pharmacological Therapy in Complex Regional Pain Syndrome (CRPS) Type I

Single session repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) is effective in the treatment of chronic pain patients but the analgesic effect of repeated sessions is still unknown We evaluated the effects of rTMS in patients with refractory pain due to complex regional pain syndrome (CRPS) type I Twenty three patients presenting CRPS type I of 1 upper limb were treated with the best medical treatment (analgesics and adjuvant medications physical therapy) plus 10 daily sessions of either real (r) or sham (s) 10Hz rTMS to the motor cortex (M1) Patients were assessed daily and after 1 week and 3 months after the last session using the Visual Analogical Scale (VAS) the McGill Pain Questionnaire (MPQ) the Health Survey 36 (SF 36) and the Hamilton Depression (HDRS) During treatment there was a significant reduction in the VAS scores favoring the r rTMS group mean reduction of 4 65 cm (50 9%) against 2 18 cm (24 7%) in the s rTMS group The highest reduction occurred at the tenth session and correlated to improvement in the affective and emotional subscores of the MPQ and SF 36 Real rTMS to the M1 produced analgesic effects and positive changes in affective aspects of pain in CRPS patients during the period of stimulation Perspective This study shows an efficacy of repetitive sessions of high frequency rTMS as an add on therapy to refractory CAPS type I patients It had a positive effect in different aspects of pain (sensory discriminative and emotional affective) It opens the perspective for the clinical use of this technique (C) 2010 by the American Pain Society

Usefulness of MLPA in the detection of SHOX deletions

SHOX haploinsufficiency causes a wide spectrum of short stature phenotypes, such as Leri-Weill dyschondrosteosis (LWD) and disproportionate short stature (DSS). SHOX deletions are responsible for approximately two thirds of isolated haploinsufficiency; therefore, it is important to determine the most appropriate methodology for detection of gene deletion. In this study, three methodologies for the detection of SHOX deletions were compared: the fluorescence in situ hybridization (FISH), microsatellite analysis and multiplex ligation-dependent probe amplification (MLPA). Forty-four patients (8 LWD and 36 DSS) were analyzed. The cosmid LLNOYCO3`M`34F5 was used as a probe for the FISH analysis and microsatellite analysis were performed using three intragenic microsatellite markers. MLPA was performed using commercial kits. Twelve patients (8 LWD and 4 DSS) had deletions in SHOX area detected by MLPA and 2 patients generated discordant results with the other methodologies. In the first case, the deletion was not detected by FISH. In the second case, both FISH and microsatellite analyses were unable to identify the intragenic deletion. In conclusion, MLPA was more sensitive, less expensive and less laborious; therefore, it should be used as the initial molecular method for the detection of SHOX gene deletion. (C) 2010 Elsevier Masson SAS. All rights reserved.

Impact on Dyslipidemia of the Laparoscopic Ileal Interposition Associated to Sleeve Gastrectomy in Type 2 Diabetic Patients

Dyslipidemia is known to increase significantly the odds of major cardiovascular events in the general population. Its control becomes even more important in the type 2 diabetic (T2DM) population. Bariatric surgeries, especially gastric bypass, are effective in achieving long-term control of dyslipidemia in morbidly obese patients. The objective of the study was to evaluate the control of dyslipidemia in patients with T2DM and BMI below 30 that were submitted to the laparoscopic ileal interposition associated to sleeve gastrectomy. An observational transversal study was performed in a tertiary care hospital, between June 2005 and August 2007. Mean follow-up was 24.5 months (range 12-38). The procedure was performed in 72 patients: 51 were men and 21 were women. Mean age was 53.1 years (38-66). Mean BMI was 27 kg/m(2) (22.1-29.4). Mean duration of T2DM was 10.5 years (3-22). Mean HbA1c was 8.5%. Hypercholesterolemia was diagnosed in 68% of the patients and hypertriglyceridemia in 63.9%. Mean postoperative BMI was 21.2.kg/m(2) (17-26.7). Mean postoperative HbA1c was 6.1%, ranging 4.4% to 8.3%. Overall, 86.1% of the patients achieved an adequate glycemic control (HbA1c < 7) without anti-diabetic medication. HbA1c below 6 was achieved by 50%, 36.1% had HbA1c between 6 and 7, and 13.9% had HbA1c above 7. Total hypercholesterolemia was normalized in 91.8% and hypertriglyceridemia in 89.1% of patients. Low-density lipoprotein below 100 mg/dl was seen in 85.7%. The laparoscopic ileal interposition associated to sleeve gastrectomy was an effective operation for the regression of dyslipidemia and T2DM in a non-obese population.