DISTORTION MAPS FROM PREFERENTIAL HYPERACUITY PERIMETRY ARE HELPFUL IN MONITORING FUNCTIONAL RESPONSE TO LUCENTIS THERAPY

Purpose: To use preferential hyperacuity perimetry to obtain a quantitative measure of central visual field distortion that would aid in the monitoring of functional responsiveness to ranibizumab treatment.

Isotopic composition of inorganic carbon as an indicator of benzoate degradation by Pseudomonas putida: temperature, growth rate and pH effects.

Degradation experiments of benzoate by Pseudomonas putida resulted in enzymatic carbon isotope fractionations. However, isotopic temperature effects between experiments at 20 and 30 °C were minor. Averages of the last three values of the CO2 isotopic composition (δ13CCO2(g)) were more negative than the initial benzoate δ13C value (−26.2‰ Vienna Pee Dee Belenite (VPDB)) by 3.8, 3.4 and 3.2‰ at 20, 25 and 30 °C, respectively. Although the maximum isotopic temperature difference found was only 0.6‰, more extreme temperature variations may cause larger isotope effects. In order to understand the isotope effects on the total inorganic carbon (TIC), a better measure is to calculate the proportions of the inorganic carbon species (CO2(g), CO2(aq) and HCO3−) and to determine their cumulative δ13CTIC. In all three experiments δ13CTIC was more positive than the initial isotopic composition of the benzoate at a pH of 7. This suggests an uptake of 12C in the biomass in order to match the carbon balance of these closed system experiments.

Mosaic monosomy 14: clinical features and recognizable facies

A 1-year-old child with clinical features of monosomy 14 is reported. She has dysmorphic facial features including ocular colobomata, dolichocephaly and microcephaly, retinal pigmentation, severe seizures, fair curly hair and tapering fingers. There was severe mental retardation. This is the first reported case of severe mosaic monosomy 14, with up to 30% mosaicism. A recognizable facial gestalt is present in children with 14q deletions or partial monosomy 14, as well as susceptibility to infection, feeding difficulties, seizures and retinal pigmentation. (C) 2004 Lippincott Williams Wilkins.

An Irish three-generation family of Cornelia de Lange syndrome displaying autosomal dominant inheritance

The existence of familial de Lange syndrome has been documented in sibs and in parent-child families, but the inheritance pattern continues to be the cause of much debate. We describe a classically affected neonate with de Lange syndrome, an affected mother and probably affected maternal grandmother. These cases show evidence for a dominantly inherited syndrome with a de Lange phenotype.

Impaired endothelium-dependent vasodilatation is a novel predictor of mortality in intensive care

Objective: Endothelial function may be impaired in critical illness. We hypothesized that impaired endothelium-dependent vasodilatation is a predictor of mortality in critically ill patients.
Design: Prospective observational cohort study.
Setting: Seventeen-bed adult intensive care unit in a tertiary referral university teaching hospital. Patients: Patients were recruited within 24 hrs of admission to the intensive care unit.
Interventions: The SphygmoCor Mx system was used to derive the aortic augmentation index from radial artery pulse pressure waveforms. Endothelium-dependent vasodilatation was calculated as the change in augmentation index in response to an endothelium-dependent vasodilator (salbutamol).
Measurements and Main Results: Demographics, severity of illness scores, and physiological parameters were collected. Statistically significant predictors of mortality identified using single regressor analysis were entered into a multiple logistic regression model. Receiver operator characteristic curves were generated. Ninety-four patients completed the study. There were 80 survivors and 14 nonsurvivors. The Simplified Acute Physiology Score II, the Sequential Organ Failure Assessment score, leukocyte count, and endothelium-dependent vasodilatation conferred an increased risk of mortality. In logistic regression analysis, endothelium-dependent vasodilatation was the only predictor of mortality with an adjusted odds ratio of 26.1 (95% confidence interval [CI], 4.3-159.5). An endothelium-dependent vasodilatation value of 0.5% or less predicted intensive care unit mortality with a sensitivity of 79% (CI, 59-88%) and specificity of 98% (CI, 94-99%).
Conclusions: In vivo bedside assessment of endothelium-dependent vasodilatation is an independent predictor of mortality in the critically ill. We have shown it to be superior to other validated severity of illness scores with high sensitivity and specificity.

The Role of Direct Presentation by Donor Dendritic Cells in Rejection of Minor Histocompatibility Antigen-Mismatched Skin and Hematopoietic Cell Grafts

Background. The success of transplantation is hampered by rejection of the graft by alloreactive T cells. Donor dendritic cells (DC) have been shown to be required for direct priming of immune responses to antigens from major histocompatibility complex-mismatched grafts. However, for immune responses to major histocompatibility complex-matched, minor histocompatibility (H) antigen mismatched grafts, the magnitude of the T-cell response to directly presented antigens is reduced, and the indirect pathway is more important. Therefore, we aimed to investigate the requirement for donor DC to directly present antigen from minor H antigen mismatched skin and hematopoietic grafts.

Desmoplastic Small Round Cell Tumor of Major Salivary Glands: Report of 1 Case and a Review of the Literature

Desmoplastic small round cell tumor is a rare malignant neoplasm mostly occurring in the vicinity of or within the peritoneal cavity, and is uncommon in the head and neck region. Tumor location within a major salivary gland is exceptional. We report a case of a 41-year-old Chinese man with a history of diabetes mellitus and end-stage renal failure on peritoneal dialysis with a desmoplastic small round cell tumor occurring in the left submandibular gland. Fine-needle aspiration cytology showed variably cohesive clusters of small cells with hyperchromatic nuclei and fine granular chromatin. On histology the neoplasm displayed classic features of a desmoplastic small round cell tumor with angulated nests of small round blue cells in a fibromyxoid/desmoplastic stroma. Neoplastic cells were immunoreactive for cytokeratins (AE1/3), desmin (paranuclear dot-like), WT-1 (nuclear), epithelial membrane antigen, and CD56. EWS gene translocation and EWS-WT1 gene fusion were detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. The case presented is the sixth case of and the oldest reported patient with a desmoplastic small round cell tumor occurring in a major salivary gland to date. Desmoplastic small round cell tumor should be considered in the differential diagnosis of a salivary gland neoplasm with a basaloid or small cell pattern on fine-needle aspiration cytology.

Impact of Sample Heterogeneity on Methylation Analysis

The recent emergence of high-throughput arrays for methylation analysis has made the influence of tumor content on the interpretation of methylation levels increasingly pertinent. However, to what degree does tumor content have an influence, and what degree of tumor content makes a specimen acceptable for accurate analysis remains unclear. Taking a systematic approach, we analyzed 98 unselected formalin-fixed and paraffin-embedded gastric tumors and matched normal tissue samples using the Illumina GoldenGate methylation assay. Unsupervised hierarchical clustering showed 2 separate clusters with a significant difference in average tumor content levels. The probes identified to be significantly differentially methylated between the tumors and normals also differed according to the tumor content of the samples included, with the sensitivity of identifying the

Reliability of tissue microarrays in detecting protein expression and gene amplification in breast cancer

Tissue microarrays allow high throughput molecular profiling of diagnostic or predictive markers in cancer specimens and rapid validation of novel potential candidates identified from genomic and proteomic analyses in a large number of tumor samples. To validate the use of tissue microarray technology for all the main biomarkers routinely used to decide breast cancer prognostication and postsurgical adjuvant therapy, we constructed a tissue microarray from 97 breast tumors, with a single 0.6 mm core per specimen. Inummostaining; of tissue microarray sections and conventional full sections of each tumor were performed using well-characterized prognostic markers (estrogen receptor ER, progesterone receptor PR and c-erbB2). The full section versus tissue microarray concordance for these stains was 97% for ER, 98% for PR, and 97% for c-erbB2, respectively, with a strong statistical association (kappa value more than 0.90). Fluorescence in situ hybridization analysis for HER-2/neu gene amplification from the single-core tissue microarray was technically successful in about 90% (87/97) of the cases, with a concordance of 95% compared with parallel analyses with the full sections. The correlation with other pathological parameters was not significantly different between full-section and array-based results. It is concluded that the constructed tissue microarray with a single core per specimen ensures full biological representativeness to identify the associations between biomarkers and clinicopathological parameters, with no significant associated sampling bias.

Nonacid reflux episodes reaching the pharynx are important factors associated with cough.

Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. Methods: Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. Results: A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P

Seasonality of cutaneous melanoma diagnosis in Northern Ireland with a review

In light-skinned populations, the incidence of cutaneous melanoma is highest in summer and lowest in winter. We analyzed the seasonal variation of melanoma incidence in Northern Ireland from 1984 to 2006 according to the Breslow thickness and body site. We also reviewed earlier studies on seasonal variation in the diagnosis of melanoma. Two-thirds of melanomas in women (2028 cases) and one-third of melanomas in men (1230 cases) were diagnosed on the limbs. In both sexes, pronounced seasonal variations were observed in the incidence of invasive melanomas less than 2mm arising on the limbs. These seasonal variations were mainly noticeable in women of all ages, to a lesser degree in men aged below 50 years, and not in men aged above 50 years. No seasonal variation was observed for melanomas less than 2mm arising on the trunk or the head and neck nor for melanomas 2mm thickness or more, irrespective of the age, sex, and body site. Seasonal variations of thin melanomas were less noticeable in men because of the axial predominance of melanoma occurrence in this sex. The review of 15 earlier studies found by a systematic search of Medline supported the likelihood of our findings. This analysis suggests that ultraviolet radiation has a short-term promotional effect on melanocytes or nevocytes of the limbs, and is not associated with progression from thin to thick melanoma. Melanoma Res 21:144-151 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.