Repeat Stereotactic Radiosurgery for Acoustic Neuromas.

Purpose
To evaluate the outcome of repeat stereotactic radiosurgery (SRS) for acoustic neuromas, we assessed tumor control, clinical outcomes, and the risk of adverse radiation effects in patients whose tumors progressed after initial management.

Methods and Materials
During a 21-year experience at our center, 1,352 patients underwent SRS as management for their acoustic neuromas. We retrospectively identified 6 patients who underwent SRS twice for the same tumor. The median patient age was 47 years (range, 35–71 years). All patients had imaging evidence of tumor progression despite initial SRS. One patient also had incomplete surgical resection after initial SRS. All patients were deaf at the time of the second SRS. The median radiosurgery target volume at the time of the initial SRS was 0.5 cc and was 2.1 cc at the time of the second SRS. The median margin dose at the time of the initial SRS was 13 Gy and was 11 Gy at the time of the second SRS. The median interval between initial SRS and repeat SRS was 63 months (range, 25–169 months).

Results
At a median follow-up of 29 months after the second SRS (range, 13–71 months), tumor control or regression was achieved in all 6 patients. No patient developed symptomatic adverse radiation effects or new neurological symptoms after the second SRS.

Conclusions
With this limited experience, we found that repeat SRS for a persistently enlarging acoustic neuroma can be performed safely and effectively.

Modelling the Geometry of the Repeat Unit Cell of Three-Dimensional Weave Architectures,

The three-dimensional (3D) weaving process offers the ability to tailor the mechanical properties via design of the weave architecture. One repeat of the 3D woven fabric is represented by the unit cell. The model accepts basic weaver and material manufacturer data as inputs in order to calculate the geometric characteristics of the 3D woven unit cell. The specific weave architecture manufactured and subsequently modelled had an angle interlock type binding configuration. The modelled result was shown to have a close approximation compared to the experimentally measured values and highlighted the importance of the representation of the binder tow path.

The Influence of COX-2 Single Nucleotide Polymorphisms on Abdominal Aortic Aneurysm Development and the Associated Inflammation

Introduction: Cyclooxygenase (COX)-2 influences cardiovascular disease and serum concentration of high-sensitivity C-reactive protein (hsCRP). The study purpose was to determine the influence of single nucleotide polymorphisms (SNPs) of the COX-2 gene on abdominal aortic aneurysm (AAA) development and serum hsCRP concentrations. Patients and Methods: Patients with AAA and disease-free controls were recruited. High-sensitivity C-reactive protein was measured by an enzyme-linked immunosorbent assay (ELISA) test. The distributions of COX-2 SNPs were investigated (rs20417 and rs4648307). The influence of the COX-2 SNPs on the hsCRP serum concentration was assessed.Results: A total of 230 patients with AAA and 279 controls were included. No difference was found in the genotype distribution of the COX-2 SNPs rs20417 (P = .26) and rs4648307 (P = .90). They did not influence the hsCRP concentration (P = .24 and P = .61, respectively). Haplotype analysis of COX-2 SNPs revealed no difference. Conclusion: These COX-2 SNPs do not play any role in AAA development and do not influence serum hsCRP. These results differentiate AAA development from atherosclerotic diseases.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009

Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P=0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats. (C) 2003 Wiley-Liss, Inc.

Is the histidine triad nucleotide-binding protein 1 (HINT1) gene a candidate for schizophrenia?

Background: The histidine triad nucleotide-binding protein 1, HINT1, hydrolyzes adenosine 5'monophosphoramidate substrates such as AMP-morpholidate. The human HINT1 gene is located on chromosome 5q31.2, a region implicated in linkage studies of schizophrenia. HINT1 had been shown to have different expression in postmortem brains between schizophrenia patients and unaffected controls. It was also found to be associated with the dysregulation of postsynaptic dopamine transmission, thus suggesting a potential role in several neuropsychiatric diseases.

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1-4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

Detection of DNA base variation and cytosine methylation at a single nucleotide site using a highly sensitive fluorescent probe

A fluorescent DNA probe containing an anthracene group attached via an anucleosidic linker can identify all four DNA bases at a single site as well as the epigenetic modification C/5-MeC via a hybridisation sensing assay.