Inclusion body myositis with abundant ring fibers

Summary A 37-year-old male presenting with a 7-year history of leg weakness was found to have moderate weakness confined to the quadriceps and myopathic changes on electromyography. Serum creatine phosphokinase was 2130 units/liter. Biopsy of the quadriceps muscle revealed an inflammatory myopathy with cytoplasmic and nuclear filamentous inclusions characteristic of inclusion body myositis. An unusual finding was the large proportion of ring fibers along with severe atrophy and fibrosis. The pathogenesis of the ring fibers in this setting is discussed.     

Transient fluorescence in synchronously dividing Escherichia coli.

Using a spectrometer equipped with an optical multichannel analyzer as the detector, we observed the Stokes laser-Raman spectra of metabolically synchronous Escherichia coli from 100 to 2100 cm-1. After more than 400 separate recordings, at cell concentrations of 10(7)-10(8) per ml, no Raman lines attributable to the metabolic process nor to the cells themselves were found. However, we did find that synchronous E. coli cultures become more fluorescent during a limited phase of the division cycle. This transient increase in fluorescence may be ascribed to a variation in the redox state of a chemical species within the bacteria or to a variation of the intracellular optical field. The effect is reproducible in synchronous cultures and it is not seen in asynchronous ones. The results suggest that spectral features seen in previous laser-Raman spectra of synchronous bacteria (taken with scanning monochromators) are due to a time-dependent variation in bacterial fluorescence.     

Human neonatal hydrocephalus. An electron microscopic study of the periventricular tissue

An infant of 43 weeks gestational age with severe congenital hydrocephalus was operated on for removal of a subependymal astrocytoma in the region of the foramen of Monro. A biopsy of periventricular tissue was taken from the lateral ventricle for examination by scanning and transmission electron microscopy. The ependyma was largely denuded, with glial cell processes forming most of the ventricular lining. Many of the attenuated ependymal cells, however, had intact junctional complexes at areas of contact with other ependymal cells. Club-shaped unipolar cells, believed to be a previously undescribed form of immature ependymal cells, were found in the ventricular lining. Cerebrospinal fluid edema was present in the neuropil up to 60 microns from the ventricular lumen, but there was no obvious axonal pathology in the tissues examined.     

Quantification of abnormal intracranial pressure waves and isotope cisternography for diagnosis of occult communicating hydrocephalus

Nineteen consecutive patients with suspected occult communicating hydrocephalus were investigated by means of clinical evaluation, neuropsychological testing, isotope cisternography, computed tomography scanning, and continuous intracranial pressure monitoring. Semi-quantitative grading systems were used in the evaluation of the clinical, neuropsychological, and cisternographic assessments. Clinical examination, neuropsychological testing, and computed tomography scanning were repeated 3 months after ventriculoperitoneal shunting. All patients showed abnormal intracranial pressure waves and all improved after shunting. There was close correlation between number, peak, and pulse pressures of B waves and the mean intracranial pressure. However, quantification of B waves by means of number, frequency, and amplitude did not help in predicting the degree of clinical improvement postshunting. The most sensitive predictor of favorable response to shunting was enlargement of the temporal horns on computed tomography scan. Furthermore, the size of temporal horns correlated with mean intracranial pressure. There was no correlation between abnormalities on isotope cisternography and clinical improvement.     

Signal peptide mutations in RANK prevent downstream activation of NF‐κB

Familial expansile osteolysis and related disorders are caused by heterozygous tandem duplication mutations in the signal peptide region of the gene encoding receptor activator of NF‐κB (RANK), a receptor critical for osteoclast formation and function. Previous studies have shown that overexpression of these mutant proteins causes constitutive activation of NF‐κB signaling in vitro, and it has been assumed that this accounts for the focal osteolytic lesions that are seen in vivo. We show here that constitutive activation of NF‐κB occurred in HEK293 cells overexpressing wild‐type or mutant RANK but not in stably transfected cell lines expressing low levels of each RANK gene. Importantly, only cells expressing wild‐type RANK demonstrated ligand‐dependent activation of NF‐κB. When overexpressed, mutant RANK did not localize to the plasma membrane but localized to extensive areas of organized smooth endoplasmic reticulum, whereas, as expected, wild‐type RANK was detected at the plasma membrane and in the Golgi apparatus. This intracellular accumulation of the mutant proteins is probably the result of lack of signal peptide cleavage because, using two in vitro translation systems, we demonstrate that the mutations in RANK prevent cleavage of the signal peptide. In conclusion, signal peptide mutations lead to accumulation of RANK in the endoplasmic reticulum and prevent direct activation by RANK ligand. These results strongly suggest that the increased osteoclast formation/activity caused by these mutations cannot be explained by studying the homozygous phenotype alone but requires further detailed investigation of the heterozygous expression of the mutant RANK proteins. © 2011 American Society for Bone and Mineral Research     

Elastic scattering spectroscopy for the diagnosis of colonic lesions: initial results of a novel optical biopsy technique

BACKGROUND: Biopsy and polypectomy frequently are performed for lesions that carry a low risk of malignant transformation in the colon. Elastic scattering spectroscopy (ESS) is a novel optical biopsy technique that can distinguish, almost instantaneously, between normal and abnormal tissue in vivo, without the need to remove tissue. We assessed the diagnostic potential of ESS in the colon to differentiate normal colonic mucosa, chronic colitis, hyperplastic polyps, adenomatous polyps (with dysplasia), and adenocarcinoma. METHODS: ESS spectra were obtained from 138 sites in 45 patients at colonoscopy. They were then compared with conventional biopsy specimens taken from the same site, including normal colonic mucosa, hyperplastic polyps, adenomatous polyps, chronic colitis, and colon cancer. Spectral analysis was carried out with a validated computerized model that used principal component analysis followed by linear discriminant analysis. Cross validation was carried out by using 60% of the data as a "training set" and the remaining 40% of the data as a "test set." RESULTS: A total of 483 spectra were analyzed (290 normal, 19 hyperplastic, 69 adenomatous polyps, 74 chronic colitis, and 31 colorectal cancer). The sensitivity and the specificity of differentiating adenomas from hyperplastic polyps was 84% and 84%, respectively; for cancer from adenomatous polyps, 80% and 75%, respectively; for colitis from normal tissue, 77% and 82%, respectively; and for dysplastic mucosa (from polyps) from colitis, 85% and 88%, respectively. CONCLUSIONS: ESS holds promise for differentiating colonic lesions with good accuracy and, therefore, is a potentially useful tool to make an instantaneous diagnosis during colonoscopy. It could prove a valuable aid for targeting biopsies in dysplasia surveillance in inflammatory bowel disease and for deciding which small polyps should be removed.     

National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease

A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre-clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP-43 inclusions, and recommend standard approaches for the workup of cases and their clinico-pathologic correlation.     

Some perspectives for the analysis of health management in São Paulo State (Brazil)

The current study aims to reflect the changes made in Secretaria do Estado da Saúde de S?o Paulo (SES) (S?o Paulo's Health State Secretariat, Brazil) related to the theoretical management proposals. A brief bibliography research was done, in Lilacs and Scielo databases. Twenty two bibliography sources from the period of 1993 to 2007 were selected. The results have shown that the main trends in the management of public administration are represented by the separation between the political and administrative functions, distinction between state exclusive activities from the ones that can be accomplished by other workers, emphasis of procedure control to product control, clear result attribution, definition of rendering account forms, governability and governing. It has been concluded that the redefinition and direction of several functions of the SES' management allowed the continuity of the decentralization processes so that health actions coverage is enlarged and it makes possible the attention inequalities decrease and promotes the equality in the health processes through an articulated management between states and cities.