The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2

Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.     

Analysis of depressed cell-mediated immunity in asbestos workers

To explore the mechanisms of asbestos-related perturbations of the immune system, we evaluated the in vitro cell-mediated immunity of five asymptomatic asbestos workers with hypergammaglobulinemia and decreased T-cell numbers. These results were compared with those in 10 matched controls. Analysis of T-lymphocyte populations revealed decreased absolute numbers of OKT4+ (helper/inducer) T cells in the peripheral blood and phytohemagglutinin (PHA)-stimulated mononuclear cell cultures of the workers. When chrysotile asbestos was added to PHA cultures, expansion of OKT4+ cell populations was disproportionately inhibited in workers' cultures. Furthermore, control proliferative responses to PHA became indistinguishable from initial worker responses. These effects were incompletely explained by the cytotoxic effects of asbestos on cultured lymphocytes. We conclude that both in vivo and in vitro exposure of mononuclear cell populations to asbestos may lead to a diminution of helper-inducer T-cell numbers. In asbestos-exposed individuals, this latter lymphocyte subpopulation appears to be especially sensitive to in vitro asbestos exposure. Although the clinical implications of these findings are unclear, we hypothesize that many of the immunologic abnormalities that occur in asbestos workers could be explained by direct asbestos effects on the OKT4+ immunoregulatory population.     

Loss of alleles in vestibular schwannomas: use of microsatellite markers on chromosome 22

OBJECTIVE: Using highly informative microsatellite markers flanking the neurofibromatosis type 2 gene, we determined the frequency of chromosome 22 allele loss in vestibular schwannomas. DESIGN: Peripheral lymphocyte/vestibular schwannoma DNA pairs were analyzed with five different microsatellite markers on chromosome 22. PATIENTS: Samples were taken from 32 patients (17 females and 15 males). Twenty-seven tumors occurred sporadically, and five were from patients with neurofibromatosis type 2. RESULTS: Using the microsatellite markers D22S351, CRYB2, D22S268, D22S304, and interleukin type 2RP3, we found loss of heterozygosity for at least two markers in 12 tumors. Ten tumors showed loss of heterozygosity for markers flanking the neurofibromatosis type 2 gene. Although microsatellite markers require little DNA for analysis and are highly informative, allele patterns may be difficult to interpret in some cases. CONCLUSIONS: Loss of heterozygosity of chromosome 22 alleles was a frequent event in vestibular schwannomas. In 10 tumors, heterozygosity was lost for centromeric and telomeric markers indicating likely monosomy 22. However, 63% of tumors did not reveal a detectable chromosomal loss. Unless a second vestibular schwannoma locus exists, these tumors likely harbor point mutations in the neurofibromatosis type 2 gene or deletions below the level of resolution of the markers used in this study.     

Essential Oils of Annual Sideritis Species Growing in Turkey

Water distilled essential oils of five annual Sideritis species collected from different regions of Turkey were analysed by GC/MS. Results are tabulated and compared with main components of the essential oils of perennial Sideritis species from Turkey.     

Health care costs and comorbidities for patients with inclusion body myositis

Objective: This study identifies the health care costs and utilization, as well as comorbidities, in a Medicare population of inclusion body myositis (IBM) patients.

Methods: Medicare patients aged ≥65 years with a diagnosis claim for IBM were identified and matched to a cohort of non-IBM patients based on age, sex, race, calendar year and census region. Generalized linear models were used to estimate health care costs and utilization during the follow-up period.

Results: The prevalence of IBM in this population, aged ≥65 years, was 83.7 cases per 1 million patients. Mean 1 year costs for the IBM cohort (N?=?361) were $44,838 compared to $10,182 for the matched non-IBM cohort (N?=?1805), an excess of $34,656. IBM was significantly associated with multiple unsuspected comorbidities, including hypertension (66% vs. 22%), hyperlipidemia (47% vs. 18%) and myocardial infarction (13% vs. 2%) (all p?Conclusions: IBM patients utilize more health care resources and incur higher health care costs than patients without IBM. Furthermore, IBM patients were more likely to have multiple comorbidities, including cardiovascular risk factors and events, muscle and joint pain, and pulmonary complications compared to those without IBM.

Limitations: The presence of a diagnosis code for a condition on a medical claim does not necessarily indicate the presence of the disease condition because the diagnosis code could be incorrectly entered in the database. Clinical and disease-specific parameters were not available in the claims data. Additionally, due to the observational study design, the analysis may be affected by unobserved differences between patients.