Correlation between regional myasthenic weakness and mental aspects of quality of life

Here we report how the different types of regional muscle involvement, i.e. bulbar, ocular or generalized, in patients with myasthenia gravis (MG) influence the mental aspects of quality of life. Clinical examination according to Osserman was performed in 48 MG patients (45 women, three men; mean age 54, SD 12 years). Each patient was at the time for clinical evaluation asked to fill out the disease-specific Myasthenia Gravis Questionnaire (MGQ) and the Short-Form 36-item questionnaire for health survey (SF-36) as patient-oriented tools. We related the regional domains (generalized domain, bulbar domain and ocular domain) of the MGQ and the clinical findings, respectively, with mental quality of life as assessed by SF-36. Bulbar and generalized involvement results in impairment of mental aspects of quality of life, whereas ocular involvement does not.     

Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.     

Double germline mutations in the RET Proto-oncogene in MEN 2A and MEN 2B kindreds.

Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all thyroid malignancies. It occurs mostly as a sporadic tumor or in association with autosomal dominant inherited cancer syndromes--multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in exons 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene are found in most of the familial cases. There are only a few published data reporting multiple germline mutations in the RET proto-oncogene. We have detected double germline mutations in 2 different exons on the same RET allele in two MEN 2 families. In the MEN 2A family, double germline mutation in exons 10 (Cys620Phe) and 13 (Tyr791Phe) was detected. In the MEN 2B family, beside the classical germline mutation in exon 16 (Met918Thr) a second germline mutation in exon 13 (Tyr791Phe) was found. This study revealed that MEN 2 syndromes can also be caused by double germline mutations in the RET proto-oncogene and these families can be added to small worldwide cohort of families with multiple germline mutations.     

Did the gradual loss of GLUT2 cause a shift to diabetic disorders in the New Zealand obese mouse (NZO/Hl)?

The New Zealand obese mouse (NZO/Hl) is characterised by hereditary obesity and type-2 diabetes, including insulin resistance, hyperinsulinaemia, and glucose intolerance. In other diabetic models, it has been revealed that the proper functioning of the glucose transporter isoform 2 (GLUT2) is essential for adequate secretion of insulin. The aim of this study was to compare the distribution of islet cells and GLUT2, as well as the expression of GLUT2-mRNA, in the pancreas of NZO mice and metabolically unimpaired NMRI (Naval Medical Research Institute) mice. Pancreas tissue was obtained from different stages of development. For molecular determination of the expression level of GLUT2-mRNA, total-RNA was extracted from the pancreas and analysed by quantitative real-time RT-PCR. All investigated NZO mice displayed increased weight, elevated hyperinsulinaemia, and slightly enhanced blood glucose levels compared with the NMRI control mice. By means of immunofluorescence microscopy drastically reduced insulin levels were detected, which might be compensated by the observed islet cell hyperplasia and hypertrophy. Furthermore, the normally peripheral localisation of the alpha-cells within islets was disturbed. By contrast, there were no changes in somatostatin cell distribution. However, considerable differences appeared with regard to GLUT2: whereas the beta-cells of NMRI mice showed dense immunostaining of the GLUT2 transporter on the cell surface, in all age groups of NZO mice, GLUT2 on the plasma membranes was reduced and dispersed in the cytoplasm. These findings agree with the molecular biological results, which displayed decreased mRNA-expression of GLUT2. In summary, the observed alteration of islet morphology and of GLUT2 expression in diabetic mice complements our previous results from a superfusion protocol and further clarifies the mechanisms of diabetogenesis in NZO mice.     

Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections.

Levels of the soluble form of the triggering receptor expressed on myeloid cells (sTREM)-1 are elevated in severe sepsis. However, it is not known whether sTREM-1 measurements can distinguish milder bacterial infections from noninfectious inflammation. The present authors studied whether serum sTREM-1 levels differ in community-acquired pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), asthma and controls, and whether sTREM-1 may be used as a surrogate marker for the need for antibiotics. Serum sTREM-1 levels in 150 patients with pneumonia, COPD and asthma exacerbations and 62 healthy controls were measured. Serum sTREM-1 levels were significantly elevated in pneumonia (median 295.2 ng x mL(-1)), COPD (280.3 ng x mL(-1)) and asthma exacerbations (184.0 ng x mL(-1)) compared with controls (83.1 ng x mL(-1)). Levels were higher in pneumonia and Anthonisen type 1 COPD exacerbations than in type 2 and 3 COPD and asthma exacerbations. The area under the receiver operating characteristics curve for sTREM-1 as a surrogate marker for the need for antibiotics was 0.77. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 were elevated predominantly in pneumonia and Anthonisen type 1 COPD exacerbations versus type 2 and 3 chronic obstructive pulmonary disease exacerbations, asthma and controls. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 has moderate but insufficient accuracy as a surrogate marker for the need for antibiotics in lower respiratory tract infections.     

Impact of neurocognitive function on academic difficulties in pediatric bipolar disorder: A clinical translation.

BACKGROUND: Previous research has demonstrated that academic and neuropsychological functions are compromised in pediatric bipolar disorder (PBD). Investigation of the degree to which neuropsychological deficits might contribute to those academic problems is needed to aid in the recognition and intervention for school achievement difficulties in PBD. METHODS: A sample of 55 children and adolescents with PBD with and without attention-deficit/hyperactivity disorder (ADHD) (PBD group, n = 28; PBD+ADHD group, n = 27) were tested with a computerized neurocognitive battery and standardized neuropsychological tests. Age range of subjects was 7-17 years, with the mean age of 11.97 (3.18) years. Parents completed a structured questionnaire on school and academic functioning. RESULTS: Logistic regression analyses indicated that executive function, attention, working memory, and verbal memory scores were poorer in those with a history of reading/writing difficulties. A separate logistic regression analysis found that attentional dysfunction predicted math difficulties. These relationships between neuropsychological function and academic difficulties were not different in those with PBD+ADHD than in those with PBD alone. CONCLUSIONS: In PBD neuropsychological deficits in the areas of attention, working memory, and organization/problem solving skills all contribute to academic difficulties. Early identification and intervention for these difficulties might help prevent lower academic achievement in PBD.