Fast Transient Fluorescence Technique for Studying Homopolymer Mobility in a Swelling Gel

Summary: The mobility of pyrene end‐capped polystyrene (Py‐PSt) trapped in swollen polystyrene gels (PSt) was investigated. PSt gels were prepared by free radical crosslinking copolymerization (FCC) of styrene (St) and ethylene glycol dimethacrylate (EGDM). The pyrene end‐capped polystyrene was produced by atom transfer radical polymerization (ATRP). After drying, these disc‐shaped PSt gels were left in a toluene solution of Py‐PSt of various molecular weights. During this process, Py‐PSt chains were trapped in the gel. These swollen gels were re‐dried in air and then immersed in pure toluene solution for monitoring the mobility of Py‐PSt chains in and out of the gel. These reswelling experiments were performed at room temperature in real time by monitoring pyrene lifetimes outside (τ₁) and inside (τ₂) of the PSt gel by using in‐situ fast transient fluorescence (FTRF) measurements. It was observed that τ₂ values decrease as swelling proceeds; however, τ₁ values stay constant during swelling. The Li‐Tanaka equation was employed to produce the swelling parameters. The swelling time constant, τ_c was found to increase as the crosslinker density of the gels and the molecular weight, of Py‐PSt chains were increased. It was observed that the collective diffusion coefficient, D_c decreased by increasing the molecular weight by obeying D_c ≈ M^?1 law.

Position of the PSt gel in the fluorescence quartz cell before (a) and after (b) swelling. I₀ and I_p are the excitation and the emission intensities.     

Delirium and extrapyramidal symptoms due to a lithium-olanzapine combination therapy: a case report

We report an elderly patient who developed severe delirium and extrapyramidal signs after initiation of lithium-olanzapine combination. On hospital admission, serum levels of lithium were found to be 3.0 mM/L which were far above toxic level. Immediate discontinuation of both drugs resulted in complete resolution of most of the symptoms except for perioral dyskinesia which persisted for three more months. We critically discussed the differential diagnosis of lithium intoxication and assessed confounding factors which induce delirium and extrapyramidal signs related with combination therapy of lithium and olanzapine.     

Concomitant radiotherapy and hyperthermia for primary carcinoma of the vagina: a cohort study

OBJECTIVE: To evaluate the supplementary value of adding hyperthermia to radiotherapy in patients with primary vaginal cancer. STUDY DESIGN: Cohort of 44 patients diagnosed with primary vaginal cancer between 1990 and 2002 was assessed. Survival rates and median survival of patients with primary vaginal cancer undergoing radiotherapy with and without hyperthermia were compared. Hyperthermia was solely added to radiotherapy in case of a tumor size >4 cm in diameter for FIGO stage III disease. RESULTS: The calculated overall 5-year survival of primary vaginal cancer was 63%. In comparison to histologic high grade tumors, higher survival rates for histologic low grade tumors were calculated. For FIGO stage III of disease, the addition of hyperthermia to radiotherapy for tumors >4 cm in diameter resulted similar survival rates and median survival when compared to those achieved by radiotherapy as monotherapy in tumors of <4 cm in diameter. CONCLUSIONS: The addition of hyperthermia to radiotherapy might result in better survival rates in primary vaginal cancer for tumors >4 cm in diameter. The supplementary effect of hyperthermia to radiotherapy may be a feasible and beneficial approach in the treatment of vaginal cancer.     

Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia

Copy number variations (CNVs) account for a substantial proportion of human genomic variation, and have been shown to cause neurodevelopmental disorders. We sought to determine the relevance of CNVs to the aetiology of schizophrenia (SZ). Whole-genome, high-resolution, tiling path BAC array comparative genomic hybridization (array CGH) was employed to test DNA from 93 individuals with DSM-IV SZ. Common DNA copy number changes that are unlikely to be directly pathogenic in SZ were filtered out by comparison to a reference dataset of 372 control individuals analyzed in our laboratory, and a screen against the Database of Genomic Variants. The remaining aberrations were validated with Affymetrix 250K SNP arrays or 244K Agilent oligo-arrays and tested for inheritance from the parents. A total of 13 aberrations satisfied our criteria. Two of them are very likely to be pathogenic. The first one is a deletion at 2p16.3 that was present in an affected sibling and disrupts NRXN1. The second one is a de novo duplication at 15q13.1 spanning APBA2. The proteins of these two genes interact directly and play a role in synaptic development and function. Both genes have been affected by CNVs in patients with autism and mental retardation, but neither has been previously implicated in SZ.     

Mapping translocation breakpoints by next-generation sequencing

Balanced chromosome rearrangements (BCRs) can cause genetic diseases by disrupting or inactivating specific genes, and the characterization of breakpoints in disease-associated BCRs has been instrumental in the molecular elucidation of a wide variety of genetic disorders. However, mapping chromosome breakpoints using traditional methods, such as in situ hybridization with fluorescent dye-labeled bacterial artificial chromosome clones (BAC-FISH), is rather laborious and time-consuming. In addition, the resolution of BAC-FISH is often insufficient to unequivocally identify the disrupted gene. To overcome these limitations, we have performed shotgun sequencing of flow-sorted derivative chromosomes using "next-generation" (Illumina/Solexa) multiplex sequencing-by-synthesis technology. As shown here for three different disease-associated BCRs, the coverage attained by this platform is sufficient to bridge the breakpoints by PCR amplification, and this procedure allows the determination of their exact nucleotide positions within a few weeks. Its implementation will greatly facilitate large-scale breakpoint mapping and gene finding in patients with disease-associated balanced translocations.     

Diagnostic value of liquid-based (Liqui-PREP) preparations and interobserver reproducibility in fine needle aspiration cytology of the nodular thyroid lesions

The aim of this study is to define the diagnostic role of Liqui-Prep (LP) technique for the diagnosis of thyroid lesions and to assess interobserver variabilities. In all, 98 thyroid FNA (fine needle aspiration) cytology samples from 83 patients for preoperative evaluation of thyroid nodules, prepared by the LP, were examined. The LP slides were independently evaluated by three pathologists and they were classified into the five categories according to the Bethesda system. The histopathologic diagnoses were grouped as follows: benign, follicular neoplasm, and malignant. Agreements between LP and histopathologic diagnoses were investigated using kappa values. Marginal homogenity and kappa tests were used for statistical analysis for the evaluation of the agreement between the pathologists and the interobserver variability of the thyroid aspiration cytology results. The presence of nucleoli, nuclear grooving, overlapping, intranuclear inclusion, and nuclear irregularity were recorded and scored on each case based on LP slide review. Concurrences between LP and the histologic diagnoses for the three pathologists were almost perfect (k = 0.798; k = 0.826; k = 0.880). When the observers were paired there was no significant difference from the diagnostic point of view. Interobserver agreement among the three pathologists was moderate. Initially diagnostic difficulties may occur because of the inadequate experience of the pathologists concerning the evaluation of the cytologic changes associated with this new technique. Liqui-Prep technique is useful for the cytologic diagnosis of the thyroid nodules. The nuclear irregularity was the most essential feature for the differentiation of malignant lesions from follicular neoplasm by the LP method.     

A comparative study of intraductal papillary neoplasia of the biliary tract and pancreas

Intraductal papillary mucinous neoplasm of the pancreas is a rare but well-established entity in contrast to intraductal papillary mucinous neoplasm of the biliary tract. The aim of this study was to compare the clinicopathologic features of intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas. Twenty patients who underwent resection for intraductal papillary mucinous neoplasm of the biliary tract were compared with 29 cases resected for intraductal papillary mucinous neoplasm of the pancreas. Clinicopathologic characteristics and resection specimens of all patients were reassessed and immunohistochemically screened for expression of a distinct set of tumor markers. Median ages of patients with intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas were 66 and 62 years, respectively (P < .05). Twelve patients with intraductal papillary mucinous neoplasm of the biliary tract (60%) had neoplasms with infiltrating carcinoma, compared with 6 patients with intraductal papillary mucinous neoplasm of the pancreas (21%, P < .05). Cytokeratin 7 and 20 expressions were equal in biliary and pancreatic intraductal papillary mucinous neoplasms. Cytokeratin 20 expression was mainly found in intestinal-type tumors. Gastric, pancreaticobiliary, and oncocytic subtypes were all observed in the intraductal papillary mucinous neoplasm of the biliary tract group. The distribution was significantly different from the intraductal papillary mucinous neoplasm of the pancreas group. The 3-year overall survival rate of malignant biliary and pancreatic intraductal papillary mucinous neoplasm was 63% and 65%, respectively (P = .798). Positive lymph nodes and a high expression of membranous mucin were associated with a significantly shorter overall survival in patients with malignant intraductal papillary mucinous neoplasm. Finally, p53 and Ki67 proliferation index were both associated with the carcinogenesis of intraductal papillary mucinous neoplasm, whereas DPC4 and CDX2 were not. Clinicopathologic features of intraductal papillary mucinous neoplasm of the biliary tract largely resemble those of intraductal papillary mucinous neoplasm of the pancreas, although intraductal papillary mucinous neoplasm of the biliary tract was associated with a higher malignancy rate at the time of surgical treatment. The level of membranous mucin expression and positive lymph nodes are significant prognosticators in patients with malignant intraductal papillary mucinous neoplasm.     

Evaluation of CSF flow patterns of posterior fossa cystic malformations using CSF flow MR imaging

Introduction Differential radiologic diagnosis of cystic malformations of the posterior fossa is often difficult with conventional imaging techniques because of overlapping features of these entities. Posterior fossa cystic malformations occupy the cerebrospinal fluid (CSF) spaces. They may create secondary dynamic effects on the movements of CSF. The aim of this study was to investigate CSF flow alterations in posterior fossa cystic malformations with CSF flow MR imaging.Methods The study included 40 patients with cystic malformations of the posterior fossa. The patients underwent cardiac-gated phase-contrast cine MR imaging. CSF flow was qualitatively evaluated using an in-plane phase-contrast sequence in the midsagittal plane. The MR images were displayed in a closed-loop cine format.Results Twelve of the patients had communicating arachnoid cyst, seven had non-communicating arachnoid cyst, ten had mega cisterna magna, six had Dandy-Walker malformation, two had Dandy-Walker variant, and three had Blake’s pouch cyst. CSF flow MR imaging indicated the regions of no, slow or higher flow, direction of flow, and abnormal cystic fluid motion. Each malformation displayed a distinct CSF flow pattern.Conclusion Phase-contrast cine MR imaging for CSF flow evaluation may be a useful adjunct to routine MR imaging in the evaluation of the cystic malformations of the posterior fossa because it can improve the specificity in differentiating such malformations.Electronic Supplementary Material Supplementary material is available in the online version of this article at Part of this article was presented as a poster exhibition at the ESNR 28th Annual Congress and 12th Advanced Course, 11–14 September 2003, Istanbul.