Death of a classified worker probably caused by overexposure to gamma radiation.

This paper describes the case of an industrial radiographer who was seriously overexposed to gamma radiation. The exact circumstances of this exposure were not established but it was concluded that he was repeatedly irradiated probably to a total average whole body dose of at least 10 Gy over several years. Also, a much larger dose to a hand required its partial amputation. He developed myelodysplasia, which progressed to acute myeloid leukaemia from which he died. Karyotypic examination of the leukaemic blasts showed changes very similar to those associated with secondary leukaemia that may develop after radio or chemotherapy. The paper describes his medical case history, the investigation of his workplace, and the attempts to estimate his radiation dose by chromosomal analysis of blood lymphocytes and electron spin resonance of dental enamel and bone.     

Comorbidities in head and neck cancer: agreement between self-report and chart review.

OBJECTIVES: To determine the accuracy of self-reported comorbidities compared with medical record review and the clinical and sociodemographic characteristics associated with accuracy of self-reported comorbidities. STUDY DESIGN: We conducted a prospective study of 458 newly diagnosed head and neck cancer patients using self-administered questionnaire and medical chart review data. Overall and itemwise consistency between self-report and chart review was evaluated. Social, clinical, and demographic characteristics of consistent versus inconsistent responders were analyzed. RESULTS: Seventy-four percent of patients had at least one comorbidity. There was good overall consistency between self-report and chart review (kappa = 0.50). Compared with consistent responders, inconsistent responders were found to be older (P < 0.05), have lower sleep (P < 0.05) and physical activity scores (P < 0.05), be more depressed (P < 0.05), and have more severe comorbidities (P < 0.05). CONCLUSIONS AND SIGNIFICANCE: Self-report may be considered as an alternative to chart review for comorbidity assessment in head and neck cancer patients. Younger patients, those with good general health, fewer depressive symptoms, and mild comorbidities, are more likely to give responses consistent with chart review.     

The Family in Medical Decisionmaking

Should the authority to make treatment decisions be extended to the competent patient's family? Neither arguments from fairness nor communitarian concerns justify such an infringement on patient autonomy.     

Acetylcholinesterase Staining in Human Auditory and Language Cortices: Regional Variation of Structural Features

Cholinergic innervation of the cerebral neocortex arises fromthe basal forebrain and projects to all cortical regions. Acetylcholinesterase(AChE), the enzyme responsible for deactivating acetylcholine,is found within both cholinergic axons arising from the basalforebrain and a subgroup of pyramidal cells in layers III andV of the cerebral cortex. This pattern of staining varies withcortical location and may contribute uniquely to cortical microcircuitrywithin functionally distinct regions. To explore this issuefurther, we examined the pattern of AChE staining within auditory,auditory association, and putative language regions of whole,postmortem human brains. The density and distribution of acetylcholine-containing axonsand pyramidal cells vary systematically as a function of auditoryprocessing level. Within primary auditory regions AChE-containingaxons are dense and pyramidal cells are largely absent. Adjacentcortical regions show a decrease in the density of AChE-containingaxons and an increase in AChE-containing pyramidal cells. Theposterior auditory and language regions contain a relativelyhigh density of AChE-containing pyramidal cells and AChE-containingaxons. Although right and left posterior temporal regions arefunctionally asymmetrical, there is no apparent asymmetry inthe general pattern of AChE staining between homologous regionsof the two hemispheres. Thus, the pattern of AChE staining covarieswith processing level in the hierarchy of auditory corticalregions, but does not vary between the functionally distinctright and left posterior regions. An asymmetry in the size of layer III AChE-rich pyramidal cellswas present within a number of cortical regions. Large AChE-richpyramidal cells of layer III were consistently greater in sizein the left hemisphere as compared to the right. Asymmetry inlayer III pyramidal cell size was not restricted to language-associatedregions, and could potentially have a variety of etiologiesincluding structural, connectional, and activational differencesbetween the left and right hemisphere.     

MR monitoring of MR-guided radiofrequency thermal ablation of normal liver in an animal model

The purpose of this study was to determine the suitability of MRI to accurately detect radiofrequency (RF) thermoablative lesions created under MR guidance. In vivo RF lesions were created in the livers of six New Zealand White rabbits using a 2-mm-diameter titanium alloy RF electrode with a 20-mm exposed tip and a 50-W RF generator. This was performed using a 0.2T clinical C-arm MR imager for guidance and monitoring. Each animal was sacrificed and gross evaluation was performed. Histologic correlation was performed on the first two animals. The MR-compatible RF electrode was easily identified on rapid gradient-echo images used to guide electrode placement. A single lesion was created in each rabbit liver. Lesions ranged from approximately 10 to 17 mm in diameter (mean, 13.5 mm). T2-weighted and short T1 inversion recovery (STIR) images demonstrated lesions ranging in diameter from 12 to 18 mm (mean, 14.6 mm). Lesion dimensions determined from images closely correlated with those determined at gross examination with the discrepancy never exceeding 2 mm, for an r² value of .87. MRI performed at the time of MR-guided RF ablation accurately demonstrated created lesions. This modality may provide a new option for the treatment of local and regional neoplastic disease.     

Localization of tissue plasminogen activator mRNA in adult rat brain

The distribution of tissue plasminogen activator (tPA) messenger RNA in rat brain was studied using in situ hybridization with ³⁵S UTP-labeled RNA probes derived from a fulllength tPA cDNA. Sense strand controls produced low, even backgrounds, with small elevations in the hippocampus. Full-length antisense probes produced strong signals over cerebral ventricular ependyma (including ependyma of the subcommissural organ), meninges, blood vessels, and Purkinje cell layer of the cerebellum, as well as strong signals over scattered cells throughout the brain. Some of these scattered labeled cells were large with lightly stained nuclei, while others were small with darkly stained nuclei. The large labeled cells, which were probably neurons, constituted 8% and 8% of cells in the brain stem and neocortex, respectively, and 100% of Purkinje cells. The small cells, which were present in all areas of the brain, constituted 3–11 % of cells in individual brain areas.     

Molecular characterization of a consistent 4.5-megabase deletion at 4q28 in prostate cancer cells

Spectral karyotyping of prostate cell lines LNCaP, DU145, PC3, and 22RV demonstrated structural chromosome rearrangements involving the distal long arm of chromosome 4. In all but 22RV, these are nonreciprocal translocations between chromosomes 4 and 10. In 22RV, an apparently reciprocal t(2q;4q) is seen. Fluorescence in situ hybridization analysis of the chromosome 4 translocation breakpoints demonstrated that deletions were associated with all of the translocations, resulting in a net loss of chromosome material. Overlapping deletions in 4q28 approximately 34 were seen in LNCap, DU145, and 22RV, which defined an approximately 4.5-megabase pair common region of deletion. The deletion in PC3 was more proximal on 4q, involving the 4q21 approximately q26 region. A meta analysis of high-resolution definition of losses of chromosome material from published studies demonstrates that loss of 4q material may occur in at least 50% of primary tumors. This analysis defines a series of genes in the critical 4q region, which is potentially associated with prostate tumor development.     

The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells

Deletion of the gene encoding the Fc immunoglobulin G receptor IIB (FcgammaRIIB) results in a fulminant, lupus-like disease in C57BL/6 but not BALB/c mice. Here we have investigated this strain-specific, epistatic loss of tolerance using gene-targeted immunoglobulin variable heavy-chain (V(H)) alleles 3H9 or 56R, which encode DNA-specific heavy chains, expressed on the C57BL/6 or BALB/c background. The combination of C57BL/6 and V(H) 56R (B6.56R) resulted in a loss of tolerance; hybridoma and single-cell analysis indicated an FcgammaRIIB-independent difference in immunoglobulin light-chain usage, consistent with an alteration in receptor editing. FcgammaRIIB deficiency resulted in an increase in immunoglobulin G (IgG) antibodies to DNA in the serum, an increased frequency of anti-DNA-reactive IgG(+) B cells with a plasma cell phenotype and immune complex deposition in the glomeruli and renal disease in B6.56R mice. Thus, FcgammaRIIB provides a distal peripheral checkpoint to limit the accumulation of autoreactive plasma cells, thereby maintaining tolerance.