Patterns of spectrin expression in B-cell lymphomas: loss of spectrin isoforms is associated with nodule-forming and germinal center-related lymphomas.

Spectrins are a family of cytoskeletal proteins that organize and link membranes to subcellular motors and filaments. Although traditionally divided into erythroid and non-erythroid forms, the discovery of new spectrin isoforms in various tissues indicates that their distribution is not yet fully characterized. To our knowledge, there is no comprehensive analysis of spectrins in lymphoid malignancies. Using tumor microarrays of paraffin blocks, we immunohistochemically studied 10 lymph nodes with reactive lymphoid hyperplasia and 94 lymph nodes involved by B-cell malignant lymphoma. Expression of spectrins alphaI, alphaII, betaI, betaII, and betaIII was scored using a 20% cutoff for positive immunoperoxidase staining. All spectrin isoforms, except erythroid-specific alphaI spectrin, were detected in lymph nodes with reactive lymphoid hyperplasia. In contrast, various spectrins were lost in particular B-cell malignant lymphomas. Based on the absence of staining for one or more spectrin isoforms in at least 50% of cases, we identified three patterns: (1) loss of alphaII and betaII in follicular lymphoma, grades 2/3 and 3/3; nodular lymphocyte predominance Hodgkin's lymphoma; nodular sclerosis Hodgkin's lymphoma; (2) loss of betaI only in Burkitt lymphoma; and (3) loss of alphaII and betaI in mixed cellularity Hodgkin's lymphoma. In contrast, follicular lymphoma, grade 1/3 and diffuse large B-cell lymphoma retained spectrin in 67-100% of cases. The other lymphoma subtypes retained spectrin in greater than 50% of cases. We identified the loss of particular spectrin isoforms in B-cell malignant lymphomas that have a nodular growth pattern and/or are believed to arise from germinal center B-cells, that is follicular lymphoma, grades 2/3 and 3/3; Burkitt lymphoma; nodular sclerosis Hodgkin's lymphoma; mixed cellularity Hodgkin's lymphoma; and nodular lymphocyte predominance Hodgkin's lymphoma. The absence of particular spectrin isoforms may correlate with transformation or aggressive biologic behavior for some lymphoma subtypes.     

Assessing the quality of provision in community nurseries

This paper raises a number of issues in the assessment of quality of provision for pre-school children before comparing the quality of provision offered by community nurseries to that offered by traditional nursery schools. Quality at all locations was assessed using the Harms and Clifford Early Childhood Rating Scale and was found in each case to be at the good to excellent end of the range. Quality varied over time and between locations although all showed improvements by the third and final rating. It is possible to conclude that the community nursery model can provide an environment of comparable quality to that experienced in traditional nursery schools. It was also possible to conclude that quality is vulnerable to internal and external pressures and that monitoring quality can also have the effect of promoting quality when staff are able to respond to feedback from ratings.     

A method for partitioning cancer mortality trends by factors associated with diagnosis: An application to female breat cancer

U.S. cancer mortality data derived from information recorded on death certificates are frequently relied upon as an indicator of progress against cancer. A limitation of this measure is the lack of information pertaining to the onset of disease, such as year-of-diagnosis, age-at-diagnosis, stage of disease at diagnosis and histology of lesions. However, population-based cancer registries collect these types of data and allow the calculation of an incidence-file based mortality rate. This incidence-based mortality rate allows a partitioning of mortality by variables associated with the cancer onset. Breast cancer incidence-based mortality measures are created and compared to mortality rates based on death certificates over a comparable time period. Novel mortality measures, such as mortality rates by stage-at-diagnosis, age-at-diagnosis and year-of-diagnosis, are used to illustrate the value of this approach.     

Xp Microdeletion Syndrome Characterized by Pathognomonic Linear Skin Defects on the Head and Neck

Abstract: We describe a new case of a rare syndrome characterized by ocular abnormalities and pathognomonic linear skin defects. This syndrome is the result of an unbalanced translocation resulting in a deletion of the distal end of the short arm of the X chromosome. We report the thirteenth case and review the clinical and cytogenetic aspects of this disorder. In addition we discuss new findings pertaining to the histopathology of the skin lesions.     

Alternative brain organization after prenatal cerebral injury: convergent fMRI and cognitive data.

The current study presents both longitudinal behavioral data and functional activation data documenting the effects of early focal brain injury on the development of spatial analytic processing in two children, one with prenatal left hemisphere (LH) injury and one with right hemisphere (RH) injury. A substantial body of evidence has shown that adults and children with early, lateralized brain injury show evidence of spatial analytic deficits. LH injury compromises the ability to encode the parts of a spatial pattern, while RH injury impairs pattern integration. The two children described in this report show patterns of deficit consistent with the site of their injury. In the current study, their longitudinal behavioral data spanning the age range from preschool to adolescence are presented in conjunction with data from a functional magnetic resonance imaging (fMRI) study of spatial processing. The activation results provide evidence that alternative profiles of neural organization can arise following early focal brain injury, and document where in the brain spatial functions are carried out when regions that normally mediate them are damaged. In addition, the coupling of the activation with the behavioral data allows us to go beyond the simple mapping of functional sites, to ask questions about how those sites may have come to mediate the spatial functions.     

Combined tool approach is 100% successful for emergency football face mask removal.

OBJECTIVE: To compare effectiveness of two techniques for removing football face masks: cutting loop straps [cutting tool: FMXtractor (FMX)] or removing screws with a cordless screwdriver and using the FMXtractor as needed for failed removals [combined tool (CT)]. Null hypotheses: no differences in face mask removal success, removal time or difficulty between techniques or helmet characteristics. DESIGN: Retrospective, cross-sectional. SETTING: NOCSAE-certified helmet reconditioning plants. PARTICIPANTS: 600 used high school helmets. INTERVENTIONS: Face mask removal attempted with two techniques. MAIN OUTCOME MEASUREMENTS: Success, removal time, rating of perceived exertion (RPE). RESULTS: Both techniques were effective [CT 100% (300/300); FMX 99.4% (298/300)]. Use of the backup FMXtractor in CT trials was required in 19% of trials. There was significantly (P<0.001) less call for the backup tool in helmets with silver screws (6%) than in helmets with other screws (31%). Mean removal time was 44.51+/-18.79s (CT: 37.84+/-15.37s, FMX: 51.21+/-19.54s; P<0.001). RPE was different between techniques (CT: 1.83+/-1.20, FMX: 3.11+/-1.27; P<0.001). Removal from helmets with silver screws was faster (Silver=33.38+/-11.03, Others=42.18+/-17.64; P<0.001) and easier (Silver=1.42+/-0.89, Other=2.23+/-1.33; P<0.001). CONCLUSIONS: CT was faster and easier than FMX. Most CT trials were completed with the screwdriver alone; helmets with silver screws had 94% screwdriver success. Clinically, these findings are important because this and other research shows that compared to removal with cutting tools, screwdriver removal decreases time, difficulty and helmet movement (reducing potential for iatrogenic injury). The combined-tool approach captures benefits of the screwdriver while offering a contingency for screw removal failure. Teams should use degradation-resistant screws. CLINICAL RELEVANCE: Sports medicine professionals must be prepared with appropriate tools and techniques to efficiently remove the face mask from an injured football player's helmet.     

Clinical judgment remains of great value in the diagnosis of acute appendicitis.

BACKGROUND: Observation and repeated examination may lead to favourable clinical outcomes in the ever-challenging diagnosis of appendicitis. The goal of this study was to evaluate clinical performance in the diagnosis of suspected appendicitis in a centre with limited access to medical imaging technologies and to identify factors associated with complicated cases. METHODS: A retrospective review of the medical records of 211 consecutive surgical cases of suspected appendicitis, spanning an 11-year period, was performed. The delays before treatment and the subsequent patient outcomes were evaluated. RESULTS: There were 8.1% of cases with negative findings on appendectomy, 75.8% with uncomplicated appendicitis, 12.3% with complicated appendicitis and 3.8% with other surgical conditions. The delay before the first medical consultation was significantly longer in patients with complicated appendicitis. The various delays after the first medical consultation did not differ significantly between the groups. CONCLUSIONS: In the context of limited available medical imaging modalities, clinical observation was not associated with an increased incidence of complicated appendicitis. The presence of complicated appendicitis was associated with the delay before the patient's first medical consultation. Clinical judgment can be prioritized and can lead to good clinical performance in the management of patients with suspected appendicitis, with no significant increase in rates of complicated appendicitis and negative findings on appendectomy.     

Increased cell death after therapy with an Arg-Gly-Asp-linked somatostatin analog.

Receptor-targeted scintigraphy and radionuclide therapy with radiolabeled somatostatin analogs are successfully applied for somatostatin receptor-positive tumors. The synergistic effects of an apoptosis-inducing factor, for example, the Arg-Gly-Asp (RGD) motif, can increase the radiotherapeutic efficacy of these peptides. Hence, the tumoricidal effects of the hybrid peptide RGD-diethylaminetriaminepentaacetic acid (DTPA)-Tyr3-octreotate (cyclic[c](Arg-Gly-Asp-D-Tyr-Asp)-Lys(DTPA)-D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr), hereafter referred to as RGD-DTPA-octreotate, were evaluated in comparison with those of RGD (c(Arg-Gly-Asp-D-Tyr-Asp)) and Tyr3-octreotate (D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr). METHODS: The therapeutic effects of RGD-111In-DTPA-octreotate, 111In-DTPA-RGD, and 111In-DTPA-Tyr3-octreotate were investigated with various cell lines by use of a colony-forming assay, and caspase-3 activity was also determined. RESULTS: Tumoricidal effects were found with 111In-DTPA-RGD, 111In-DTPA-Tyr3-octreotate, and RGD-111In-DTPA-octreotate, in order from least effective to most effective. Also, the largest increase in caspase-3 levels was found with RGD-111In-DTPA-octreotate. CONCLUSION: RGD-111In-DTPA-octreotate has more pronounced tumoricidal effects than 111In-DTPA-RGD and 111In-DTPA-Tyr3-octreotate, because of increased apoptosis, as indicated by increased caspase-3 activity.     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.