Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.

Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus.

We carried out a prospective study of the prevalence and characteristics of anticardiolipin antibodies (aCL) and migraine on 103 consecutive patients with systemic lupus erythematosus (SLE) derived from three European referral university centers. We also included a control group of 58 patients with migraine not associated with SLE. We interviewed all patients using a data collection form designed to provide a complete record of the clinical characteristics of headache. Fifty-four (52%) patients with SLE suffered recurrent headache. We diagnosed migraine in 32 patients, tension headache in 21, and cluster headache in one. Thirty (29%) patients with SLE had aCL. Migraine was present in five patients with aCL and in 27 patients without aCL (17% versus 37%, p = 0.07). No migraine control patient had aCL. Our study highlights the frequency of headache in SLE, but does not support an association between the presence of aCL and migraine in this disease.

Antiendothelial cell antibodies in patients with the antiphospholipid syndrome.

Antiendothelial cell antibodies (AECA) have been detected in 20 out of 30 patients (67%) with thrombosis associated with antiphospholipid antibodies. Seven patients had systemic lupus erythematosus and 13 had the "primary" antiphospholipid syndrome. Seven patients had both IgG and IgM AECA, 9 had IgG AECA only, and 4 had only IgM AECA. None of 30 control patients with thrombotic events not related to antiphospholipid antibodies had a positive titre of AECA (P less than 0.001). No correlation between AECA, antinuclear antibodies, anti-dsDNA antibodies, anti-neutrophil cytoplasm antibodies, precipitating antibodies to soluble nuclear and cytoplasmic antigens or complement components was found. The possible role of these AECA in the pathogenesis of thrombotic events is discussed.

Transient global amnesia and antiphospholipid antibodies.

The patient, a 55 year-old man, developed an episode of transient global amnesia. He was a smoker and had hypercholesterolemia. He was found to have a positive rapid plasma reagin test and high levels of anticardiolipin antibodies. Other investigations were negative. The presence in this patient of antiphospholipid antibodies suggests a vascular mechanism for transient global amnesia.

[Pituitary apoplexy and empty sella]. / Apoplejía hipofisaria y silla turca vacía.

Pituitary apoplexy (PA) is currently considered as one of the causes of empty sella (ES). However, in most reported cases the diagnosis of PA was based on anamnesis. A prospective study of three patients diagnosed during the PA episode was carried out. Periodical evaluations of hormone concentrations and cerebral computed tomography images were carried out. Initially, the three patients had a global anterior pituitary developed ES within 6 and 18 months. Surgical therapy was not undertaken in any case. Owing to the rarity of the disease definitive conclusions are difficult to obtain; however, the present study suggests that after an episode of PA global anterior pituitary failure develops, with subsequent ES. Early medical therapy with glucocorticoids can avoid surgical therapy.

[Polyneuropathy associated with human immunodeficiency virus infection]. / Polineuropatía asociada a la infección por el virus de la inmunodeficiencia humana.

We report five patients with human immunodeficiency virus (HIV) infection in stages IV-C1, IV-C2 and IV-D who developed peripheral polyneuropathy (PNP). Two patients had invalidating PNP with a demyelinating predominance, while in the remaining three axonal component predominated. However, both components were present in different degrees in all patients. We have observed two cases with transition from one type of PNP to the other during the course of the disease. Inflammatory polyradiculoneuropathy usually develops in the initial stages of the infection, while the distal axonal type is more commonly seen in patients with advanced infection. The possibility that PNP could have, in these patients, a common etiology and pathogenesis with variable clinical and electrophysiological expression is discussed.

[Multi-infarct dementia associated with antiphospholipid antibodies. Presentation of 2 cases]. / Demencia multiinfártica asociada a anticuerpos antifosfolípido. Presentación de dos casos.

Two patients with positive antiphospholipid antibody and early multi-infarction dementia as a presenting feature of their illness are reported. One was included in the so called primary antiphospholipid antibody syndrome, while the second one met the criteria for systemic lupus erythematosus. We point out to the presence of aortic regurgitation in one of the patients and its possible relation with these antibodies. Although the precise mechanism of thrombosis is incompletely known, the recognition of this type of dementia is of paramount importance as it is a potentially treatable condition.

Analyzing and strengthening the vaccine safety program in Manitoba.

BACKGROUND: The emergence of a novel influenza A virus in 2009 and the rapid introduction of new pandemic vaccines prompted an analysis of the current state of the adverse events following immunization (AEFI) surveillance response in several provinces. OBJECTIVES: To highlight aspects of the situational analysis of the Manitoba Health, Healthy Living and Seniors (MHHLS's) AEFI surveillance system and to demonstrate how common business techniques could be usefully applied to a provincial vaccine safety monitoring program. METHOD: Situational analysis of the AEFI surveillance system in Manitoba was developed through a strengths-weaknesses-opportunities-threats (SWOT) analysis and informed by the National Immunization Strategy vaccine safety priorities. Strategy formulation was developed by applying the threats-opportunities-weaknesses-strengths (TOWS) matrix. RESULTS: Thirteen strategies were formulated that use strengths to either take advantage of opportunities or avoid threats, that exploit opportunities to overcome weaknesses, or that rectify weaknesses to circumvent threats. These strategies entailed the development of various tools and resources, most of which are either actively underway or completed. CONCLUSION: The SWOT analysis and the TOWS matrix enabled MHHLS to enhance the capacity of its vaccine safety program.

Kepler detected gravity-mode period spacings in a red giant star.

Stellar interiors are inaccessible through direct observations. For this reason, helioseismologists made use of the Sun's acoustic oscillation modes to tune models of its structure. The quest to detect modes that probe the solar core has been ongoing for decades. We report the detection of mixed modes penetrating all the way to the core of an evolved star from 320 days of observations with the Kepler satellite. The period spacings of these mixed modes are directly dependent on the density gradient between the core region and the convective envelope.