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Objetivo: En las últimas décadas se han identificado genes asociados a la masa ósea y al riesgo de fractura osteoporótica, varios de los cuales pertenecen a la vía de Wnt. En este proyecto se estudió la funcionalidad de 7 mutaciones de cambio de sentido del gen DKK1 –un inhibidor de la vía de Wnt– presentes en la población general. Material y métodos: Se realizaron estudios in vitro del gen reportero luciferasa para medir la actividad de la vía de Wnt en presencia o ausencia de DKK1 silvestre o mutada, y estudios de western blot, para evaluar si las distintas mutaciones afectan a su síntesis y/o a su estabilidad. Resultados: La proteína DKK1 con la variante p.Ala41Thr presenta menor actividad inhibidora de la vía en comparación con la proteína silvestre. También se observaron diferencias significativas entre los experimentos realizados en ausencia de DKK1 y los que incluyen DKK1 con la mutación p.Ala41Thr. Los western blots mostraron que la cantidad de proteína era similar para todas las variantes, tanto las mutadas como la silvestre, por lo que la pérdida de actividad de p.Ala41Thr no parecía deberse a falta de proteína. El resto de las mutaciones no presentaron un comportamiento diferente al de la proteína DKK1 silvestre. Conclusiones: La variante de cambio de sentido p.Ala41Thr de la proteína DKK1, con una frecuencia poblacional de 0,013%, presenta una pérdida parcial de su función inhibidora, que no es debida a la falta de expresión de ésta. Esta variante génica podría conllevar un aumento de la densidad mineral ósea en las personas de la población general portadoras de esta mutación.

Introduction: Anti-ganglioside antibodies (AGA) have been associated with several peripheral neuropathies, such as Miller–Fisher syndrome, Guillain–Barré syndrome and multifocal motor neuropathy. They have also been studied in patients with systemic lupus erythematosus (SLE), focusing on neuropsychiatric manifestations and peripheral neuropathy, but the results are contradictory. Objective: To study the presence of AGA in a large cohort of patients with SLE and neuropsychiatric manifestations. Patients and methods: Serum from 65 consecutive patients with SLE and neuropsychiatric manifestations, collected from 1985 to 2009, was tested for the presence of AGA antibodies (GM1, GM2, GM3, asialo-GM1 GD1a, GD1b, GD3, GT1b, GQ1b) using a standard enzyme-linked immunosorbent assay ELISA test (INCAT 1999) and thin layer chromatography (TLC). Results: Positive results for asialo-GM1 (IgM) were found in 10 patients, 6 were positive for asialo-GM1 (IgM and IgG), and 4 were positive for other AGA such as GM1, GM2, GM3, GD1b, GT1b, GD3, (mainly IgM). Conclusions: Clinical and statistical studies showed no correlation between AGA and neuropsychiatric manifestations of SLE. Although some patients showed reactivity to AGA, these antibodies are not a useful marker of neuropsychiatric manifestations in SLE patients. [ABSTRACT FROM AUTHOR]

This paper reports the successful application of ink-jet printing to the deposition of both continuous coatings and multi-filamentary structures of YBCO. Stable inks have been prepared using both the established TFA-MOD route and novel fluorine-free precursors with appropriate rheological properties for ink-jet printing. Continuous and well textured coatings with lengths exceeding 100 m and a thickness of 0.5 ͛m have been deposited by electromagnetic ink-jet printing from TFA precursors on LZO-buffered Ni-W substrates and samples have achieved a Jc around 1.5 MA cm-2 (self-field, 77 K). On single crystal substrates, continuous coatings and multi-filamentary structures have been deposited using piezoelectric ink-jet printing both from TFA- and water-based precursors, achieving Jc values up to 3 MA cm-2. [ABSTRACT FROM AUTHOR]

The evolution of valvular disease in antiphospholipid syndrome (APS) is barely known. In order to evaluate whether the presence or absence of valvular disease at the time of diagnosis of APS, assessed by an initial echocardiogram, predicts its subsequent evolution, we performed a prospective cohort study. We included 53 patients with APS. An initial transthoracic echocardiogram was performed on patients at the time of diagnosis of APS. Serial echocardiograms were conducted along a 12-year follow-up. Final echocardiograms were used for comparative purposes. We started with 29 patients (54%) with and 24 (45%) without valvulopathy at initial echo. At the final echocardiogram, 27 of 29 patients with initial valvulopathy continued to have valvular disease (a 93% observed likelihood), and 22 of 24 patients without initial valvulopathy demonstrated an absence of valvular disease (a 91% observed likelihood). Patients with valvulopathy in comparison with those without presented more arterial thrombotic events (69% vs. 20%, P<0.001), atherosclerotic risk factors (62% vs. 29%, P=0.01), livedo (48% vs. 16%, P=0.01) and migraine (41% vs. 12%, P=0.02). We have identified two subtypes of APS patients with and without valvulopathy by defining differential clinical features and with little crossover in valvular involvement over a long follow-up period, giving a high prognostic value to the initial echocardiographic assessment. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the presence of nailfold capillary abnormalities and extrahepatic signs of connective tissue disease in patients with primary biliary cirrhosis (PBC), as compared to patients with other chronic liver diseases. ƒWe evaluated 22 patients with PBC and 15 patients with other chronic liver diseases as a control group. Nailfold capillaroscopy was performed by two observers blinded to clinical findings using a Wild M3 stereomicroscope with an Intralux 5000 Volpi cold light lamp. ƒWe detected nailfold capillary abnormalities in 20 out of 22 (91%) PBC patients. Twelve of these 20 patients (54%) showed capillary alterations characteristic of systemic sclerosis. In the control group only two out of 15 patients (13%) presented alterations and in both cases they were a non-specific type. The presence of nailfold capillary abnormalities was significantly greater in PBC patients than in the control group (P<0.001). Eleven out of the 22 PBC patients (50%) had extrahepatic signs of connective tissue disease and most of them were related to systemic sclerosis; patients with other chronic liver diseases did not present rheumatic manifestations (P<0.001). In PBC patients there was a significant association between systemic sclerosis capillary pattern and rheumatic manifestations (P<0.03). ƒThe high prevalence of nailfold capillary abnormalities characteristic of systemic sclerosis in patients with PBC and the correlation with sclerodermal manifestations suggests that this capillaroscopic finding could be a useful indicator to investigate rheumatic manifestations in these patients. [ABSTRACT FROM AUTHOR]

Background: Manometric assessment of the gastro-esophageal junction (GEJ) is deceptive in that ignores key dynamic properties of the junction, such as resistance to flow and compliance. Our aim was to investigate the mechanical properties of the GEJ comprising intraluminal pressure (measured by manometry), resistance to flow and compliance (measured by resistometry). Methods: We studied 8 healthy subjects, 11 patients with achalasia and 11 patients with scleroderma. We used a pneumatic resistometer, previously developed and validated in our laboratory. The resistometer consists of a flaccid polyurethane 5-cm cylinder connected to an electronically regulated nitrogen-injection system; the instrument records nitrogen flow through the cylinder while maintaining a constant pressure gradient between its proximal and distal ends. By placing the cylinder successively in the proximal stomach and along the GEJ we measured the GEJ-gastric resistance gradient (GEJ resistance minus gastric resistance) and were able to calculate the cumulative resistance (sum of resistance exerted at each pressure level), peak resistance (at any injection pressure), nil resistance point (injection pressure in mmHg at which GEJ resistance equals gastric resistance), and compliance slope (flow/pressure relationship). Results: We found that GEJ resistance to flow (cumulative resistance, peak resistance, and nil resistance point) is significantly increased in achalasia and decreased in scleroderma (P < 0.05 versus health) while GEJ compliance is diminished in achalasia (P < 0.05 versus health) and normal in scleroderma. Conclusion: Achalasia is a disease characterized by increased GEJ resistance and rigidity. By contrast, although scleroderma is characterized by decreased GEJ resistance, GEJ compliance may be normal. [ABSTRACT FROM AUTHOR]

Pathogenesis of neuropsychiatric manifestations of systemic lupus erythematosus (SLE) has not been clearly defined, and the search for pathogenic mechanisms has focused on the importance of several autoantibodies. There is increasing evidence that antibodies against gangliosides may have a pathogenic role in some neurological disorders. The aim of the present study was to examine the association between antibodies against gangliosides and neuropsychiatric SLE. We found anti-type II ganglioside antibodies in two out of 32 patients with multiple sclerosis (6.25%) and in 10 out of 60 patients with SLE (16.6%); five of 17 patients with neurological abnormalities also had high levels of these antibodies (29.4%). Five of the 10 patients with SLE and positive antiganglioside antibody assays had only IgM antibodies, three had IgG antibodies and two had both isotypes. By chi-square analysis, the incidence of anti-type II ganglioside antibodies was not significantly higher in patients with symptoms related to the nervous system than in SLE patients without neurological involvement (P > 0.2). No clear correlation was found between antibodies against gangliosides and cardiolipin. [ABSTRACT FROM PUBLISHER]

The effects of pregnancy on the course of Behçet's disease (BD), and vice versa, are unknown and little has been reported. We have studied three groups of women: (1) group A included 61 pregnancies in 23 women with BD, 25 pregnancies took place in 10 patients already diagnosed (group 1A) and 36 pregnancies occurred in 13 patients before disease diagnosis (group 2A); (2) group B included 30 females with 83 pregnancies affected by recurrent oral ulcers (ROU); (3) group C included 20 healthy women with 61 pregnancies. We investigated the effects of BD on pregnancy and fetal outcome, and the influence of gestation on the course of BD. A questionnaire was used in which specific information about each pregnancy, labour and puerperium was collected. We looked for medical confirmation in all cases where any pathology had been identified. No significant differences were found in the incidence of pregnancy complications between groups. The incidence of perinatal death was also similar and neither congenital abnormalities nor neonatal BD were observed. Only two patients observed a flare of the disease and in two cases the diagnosis of BD was made during the pregnancy. In our series, the outcome of pregnancy was generally good in BD patients, disease manifestations were not consistently worsened and fetal outcome was excellent. The first case of Budd-Chiari syndrome during the puerperium in a BD patient is reported. [ABSTRACT FROM PUBLISHER]

Objective: To identify survival prognostic factors and markers of morbidity among patients with systemic sclerosis (SSc).Patients and Methods: The study included 72 patients diagnosed with SSc. According to the extent of skin involvement, three groups of patients were established: group 1, without sclerosis and with sclerosis of fingers and neck; group 2, with sclerosis of face and distal to elbows and knees; group 3, with generalised sclerosis including the trunk. All patients were included in a study protocol to determine visceral involvement. Cumulative survival after first symptom has been estimated according to the Kaplan-Meier method. The association between a hypothetical prognostic factor and cumulative survival after first symptom was assessed by log rank test. The association between a hypothetical risk factor and the prevalence of severe morbidity was assessed by the odds ratio. Multiple logistic regression models were used to identify the main predictors of severe morbidity.Results: Survival was estimated to be 85% 10 years after first SSc symptom. Survival was higher among SSc patients with skin involvement distal to elbows and knees than among the rest of patients; a forced vital capacity (FVC) on spirometry lower than 70% of expected value was associated with a shorter survival, even after adjustment for diffuse SSc. Skin involvement proximal to elbows or knees was associated with a higher prevalence of severe morbidity (OR = 46.57; p < 0.001). According to a multiple logistic regression, severe morbidity was higher among patients with skin involvement proximal to knees or elbows (OR = 40.92; p < 0.001) or among patients with pulmonary hypertension detected by Doppler echocardiography (OR = 23.66 p < 0.001).Conclusions: In patients with SSc the extent of skin sclerosis was found to be a determining factor on the prognosis. According to skin sclerosis extent two main subsets of SSc patients with different survival incidence and degree of morbidity could be clearly established: limited SSc, formed by patients with no skin sclerosis or with sclerosis distal to elbows and knees and diffuse SSc, formed by patients with skin sclerosis distal and proximal to elbows and knees. Moreover, lung involvement (FVC < 70% on survival study and pulmonary hypertension on morbidity study) was an important and independent prognostic factor. [ABSTRACT FROM AUTHOR]

A group of seven young women with antiphospholipid antibodies, histories of recurrent fetal loss, and no live births is reported. Two patients had systemic lupus erythematosus, and the other five fulfilled criteria for the primary antiphospholipid syndrome. A false Venereal Disease Research Laboratory (VDRL) test was present in four of the patients, three had a previous episode of arterial or venous thrombosis, or both, and two had thrombocytopenia. Prednisone and acetylsalicylic acid were given, and monthly controls of lupus anticoagulant activity were carried out. The dose of acetylsalicylic acid was fixed while the dose of steroids was adjusted according to the degree of lupus anticoagulant activity. A fetal survival was obtained in 7/9 (78%) of the pregnancies. Three of the newborn infants had transitory lupus anticoagulant activity. A search for antiphospholipid antibodies should be carried out in patients with otherwise unexplained fetal losses, falsely positive VDRL tests, thrombosis, or thrombocytopenia as the treatment of such patients with prednisone and acetylsalicylic acid is highly effective. [ABSTRACT FROM PUBLISHER]

Objective: To determine the prevalence of cardiac valvular involvement in patients with the primary antiphospholipid syndrome.Design: Cross-sectional study with evaluation of case patients and control patients by Doppler echocardiography. The mean follow-up for case patients was 22 months.Setting: University-based tertiary medical center.Patients: Twenty-eight consecutive patients who were diagnosed with the primary antiphospholipid syndrome during a 10-year period; 28 age- and sex-matched healthy controls.Measurements and Main Results: Ten patients (36%; 95% Cl, 19% to 56%) with the primary antiphospholipid syndrome had cardiac valvular involvement: Four patients had mitral valve involvement; four patients, aortic valve involvement; and two patients, both mitral and aortic valvular involvement; no patients had tricuspid or pulmonary valve disease. Eight of 10 patients had a regurgitant murmur. None of the control patients had valvular disease. The mean mitral valve thickness in patients with mitral valve involvement was 7.0 +/- 1.6 mm, compared with 2.7 +/- 0.8 mm in patients with normal valves and 3.2 +/- 0.9 mm in the control group. The mean aortic valve thickness in patients with aortic valve involvement was 3.8 +/- 0.5 mm compared with 1.4 +/- 0.3 mm in patients with normal valves and 1.4 +/- 0.5 mm in the control group. Stenotic lesions were not found. Regurgitation was severe in two patients (one required surgery), moderate in three patients, and mild in three patients.Conclusions: Valvular involvement is frequently found in patients with the primary antiphospholipid syndrome. The lesions are left-sided, causing regurgitation that may be clinically important. [ABSTRACT FROM AUTHOR]

We present the case of a 57-year old female patient diagnosed with systemic lupus erythematosus (SLE) along with glomerulonephritis and chronic intestinal pseudo-obstruction (CIPO). Dilatation of bile and pancreatic ducts not associated with malignant or litiasic obstruction is reported. The combination of bile duct associated with CIPO in a patient with lupus has not been previously reported in the literature and it probably suggests a smooth muscle dysmotility. [ABSTRACT FROM AUTHOR]

Several cases of eosinophilic conditions including Churg-Strauss syndrome (CSS) have recently been reported in asthmatic patients being treated with antileukotriene receptor antagonists. One patient with CSS who experienced a clinical relapse after treatment with montelukast and two asthmatic patients who developed CSS while receiving montelukast treatment are described. In one case reduction in the dose of oral steroid preceded the onset of CSS. To our knowledge, no case of CSS relapse has previously been reported in association with leukotriene antagonists. [ABSTRACT FROM AUTHOR]

In order to ascertain the incidence of monoclonal gammopathy (MG) in systemic lupus erythematosus (SLE), 120 SLE patients were evaluated. Four patients (3.3%), two of whom were under 50 years of age, were found to have a monoclonal immunoglobulin in their serum. Our data agree with the previous literature in demonstrating a higher incidence of MG in SLE patients in comparison with the general population. Neither the clinical importance nor the pathogenetic significance of this association is known. [ABSTRACT FROM PUBLISHER]

The case is reported of a patient who developed a vertebral osteomyelitis caused by Enterobacter cloacae. The organism was isolated in cultures of blood and vertebral puncture biopsy samples. The patient was satisfactorily treated with trimethroprim and sulphamethoxazole. Enterobacter cloacae, a Gram negative organism, has been confirmed as the cause of bacteremia in patients with burns, urinary infections, in adults with pneumonia, and in children with joint infections. Spondylodiscitis caused by Enterobacter cloacae has not previously been described. [ABSTRACT FROM AUTHOR]