Association of myopathy with large-scale mitochondrial dna duplications and deletions: Which is pathogenic?

We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50–year-old woman with an adult-onset progressive myopathy. The predominant mtDNA abnormality was a 21.2–kb duplicated molecule. In addition, a small population of the corresponding partially deleted 4.6–kb molecule was detected. Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase chain reaction analysis, COX-negative fibers contained a low number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.     

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.     

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.     

Up-regulation of nicotinic acetylcholine receptors following chronic exposure of rats to mainstream cigarette smoke or α4β2 receptors to nicotine

Smokers are reported to have a higher density of central nicotinic acetylcholine receptors (nAChRs) that non-smokers at autopsy. Whether this increased receptor density is a response to smoking or a result of genetic variability is not known. While sub-chronic treatment of rats and mice with nicotine results in upregulation of central nAChRs, changes in receptor density in response to cigarette smoke have not been studied previously. In this study, male Sprague-Dawley rats were exposed nose-only for 13 weeks to mainstream cigarette smoke followed by assessment of [³H]nicotine binding in five brain regions of smoke- and sham-exposed animals. In smoke-exposed animals, there was a significant increase in nAChR density in the cortex, striatum, and cerebellum (35, 25, and 31% increases, respectively), while there was no significant change in receptor density in the thalamus and hippocampus. Smoke exposure did not alter markedly the affinity of the receptor for nicotine in these brain regions. Furthermore, up-regulation of nAChRs did not alter the biphasic binding properties by which nicotine binds to its receptor. There were no changes in the association (fast phase) or isomerization (slow phase) rate constants, and the percent contribution of slow and fast phase binding to nAChRs was not altered in the up-regulated receptor population compared with control. Similar results were observed following chronic nicotine exposure of cultured cortical cells from fetal rat brain or cells transfected with the α4β2 nAChR subtype. These results show that the up-regulation following smoke exposure in the rat is phenomenologically similar to that observed in vitro. These data provide preliminary evidence for a relationship between cigarette smoking and nAChR up-regulation in vivo and suggest that similar mechanisms of upregulation may underlie chronic smoke exposure of live animals and nicotine exposure of artificially expressed α4β2 receptors in vitro.     

In vivo measurement of the shear modulus of the human vocal fold: interim results from eight patients

The shear modulus of the vocal fold is an essential parameter required to enhance our understanding of how the vocal fold operates, to develop mathematical models of phonatation, and to provide benchmarks to quantify the effectiveness of surgical procedures. The authors announced the successful deployment of an instrument to measure vocal fold elasticity in vivo last year, and now present the data taken from eight patients in vivo. The shear modulus was measured at the mid-membranous point, in a transverse direction with respect to the axis drawn between the anterior commissure and vocal process. The range of mean shear modulus results is 701–2,225 Pa, with a mean value of 1,371 Pa.