Adult-onset leukodystrophies from respiratory chain disorders: do they exist?

Respiratory chain disorders (RCDs) have been included in the differential diagnosis of adult-onset leukodystrophies. Here, we first report a 32-year-old female with an atypical, adult-onset, non-syndromic RCD due to a mitochondrial DNA deletion and manifesting as complicated ataxia. A ‘leukodystrophic’ pattern was found on brain MRI, but it was neither isolated nor predominant because of the presence of overt basal ganglia and infratentorial lesions, which led us to the proper diagnosis. Subsequently, we evaluated our series of patients with RCDs in order to verify whether a ‘leukodystrophic’ pattern with little or no involvement of deep grey structures and brainstem may be found in adult-onset RCDs, as reported in children. Among 52 patients with adult-onset RCDs, no case with a ‘leukodystrophic’ pattern was found, apart from three cases with a classical phenotype of mitochondrial neurogastrointestinal encephalopathy. In addition, no case of RCDs was found among six cases of adult-onset leukodystrophy of unknown origin and at least one feature suggestive of mitochondrial disease. The review of the literature was in agreement with these findings. Thus, we provide evidence that, unlike in children, RCDs should not be included in the differential diagnosis of adult-onset leukodystrophies, except when there are additional MRI findings or clinical features which unequivocally point towards a mitochondrial disorder.     

Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells.     

Racial and Socioeconomic Disparities in Access and Utilization of Adrenal Metastasectomy

World Journal of Surgery - There is substantial evidence that resecting adrenal metastases can be safely accomplished and extend overall survival in select patients. However, patient access to this...     

Olfactory perception rehabilitation after total laryngectomy (OPRAT): proposal of a new protocol based on training of sensory perception skills

European Archives of Oto-Rhino-Laryngology - We aim to propose a new protocol for olfaction rehabilitation after total laryngectomy based on training of sensory perception levels using the Nasal...     

Accuracy of commercial 24-hour electrocardiogram analyzers for quantitation of total and repetitive ventricular arrhythmias

The accuracy of 2 commercial 24-hour electrocardiogram analyzers was tested for quantitation of ventricular premature complexes (VPCs). Scanner 1 was the Cardiodata Systems Mark III and scanner 2 was the Avionics Trendsetter DCG VII. Twenty-four-hour electrocardiographic recordings from 19 consecutive ambulatory patients with frequent VPCs were analyzed by each device. Results were compared with those from hand counts of complete printouts of each of the 19 recordings. For total VPCs, scanner 1 had an average error of 13% (range 0 to 58%) and scanner 2 had an average error of 24% (range (1 to 80%). Scanner 1 had an error of more than 10% for 9 of the 19 recordings and scanner 2 more than 10% for 11 of the 19 recordings. For paired VPCs, scanner 1 had a mean error of 23% (range 4 to 77%), and scanner 2 of 56% (range 34 to 79%). For nonsustained ventricular tachycardia, scanner 1 had an average error of 20% (range 8 to 41%) and scanner 2 had an error of 56% (range 34 to 78%). Thus, when recordings from consecutive ambulatory patients with frequent VPCs were analyzed, neither device was consistently accurate for quantitation of total VPCs. Both analyzers had an unacceptable error for quantitation of repetitive VPCs. All currently available devices may have comparably large errors. This possibility is confirmed by recalculation of the reported data from a third scanner.     

Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.