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There is extensive evidence for decrements of gene expression in AD, at several levels in the process. There is also evidence for increments of expression of some genes. Message for the amyloid precursor protein (APP), for example, is elevated in surviving neurons of certain subcortical populations in AD. We evaluated expression of message for APP as well as for certain neuronal and glial cytoskeletal proteins in the cortex of six cases of AD. Neuronal mRNAs, including that for APP, were significantly decreased when compared with control cortex, whereas the glial mRNA was increased. We have projected studies to determine the evolution of these mRNA decrements in Alzheimer-type degeneration. The rationale for these studies and preliminary findings are discussed.
To define the pathology in cases of non-Alzheimer primary degenerative dementia (non-AD PDD), we have studied autopsies from four medical centres accessioned in consecutive years since 1976. Neurochemical studies of the basal forebrain-cortical (BF-C) cholinergic system have been conducted in cases from which frozen tissue was available. Twenty-two cases (mean age 70 years, range 47-86) in which the history was consistent with PDD, but which did not meet anatomic criteria for AD, were selected. Approximately 70 cases of PDD, which were accessioned in the same years and met the anatomic criteria for AD, were excluded. The pathologic findings permitted a classification into six groups: Lewy body disease (LBD), 4 cases; Pick's disease, 6 cases; cortical degeneration with motor neuron disease (CDmnd), 2 cases; hippocampal and temporal lobe sclerosis, 3 cases; few or nonspecific abnormalities, 5 cases; other disorders, 2 cases. Our findings suggest that LBD and Pick's disease account for a large proportion of cases of non-AD PDD in the presenile age group, but that a large number of other disorders occasionally present as PDD. Careful examination of the motor systems, as well as cerebral structures relate' to cognitive function, is important in the neuropathologic evaluation. Lesions of the BF-C cholinergic system have been most consistent and severe in LBD, and have not been identified in CDmnd.
Ontogenic development of granule cells in the hippocampal dentate gyrus is influenced by genes including WNT3, EMX2, NEUROD, and LEF1. Dentate granule cells continue to be generated from stem cell precursors postnatally and during adult life, and are implicated in normal and abnormal neurological function. Developmental privation of dentate granule cells is rare and essentially always occurs in the context of other neurodevelopmental abnormalities. We have found no previous reports of severe, selective agenesis of dentate granule cells in humans.
A gross and microscopic examination of the brain included appropriate histochemical and immunohistochemical preparations and examination of the hippocampal formation at multiple levels bilaterally.
This neurologically normal 82-year-old man was found to have bilateral agenesis of the hippocampal dentate gyrus, no identifiable dentate granule cells, and moderate disorganization of the pyramidal cell layer of Ammon's horn. We found no neurodevelopmental abnormalities outside the hippocampus.
The hippocampal architectural alterations in this patient are similar to those associated with a murine Lef1 mutation, but our human case does not have the other congenital deficits reported in the Lef1-null mouse. Bilateral agenesis of the hippocampal dentate gyrus, and apparent failure of regeneration of dentate granule cells from stem cells in adult life, may occur without overt clinical neurological deficits.
Nodular fasciitis is a reactive proliferation of fibroblasts/myofibroblasts characterized by a rapidly growing non-tender subcutaneous mass and subsequently self-limited course. It is commonly found on the upper extremities, face, and shoulder, although it may occur in any superficial location. Its etiology is largely unknown, but associations have been made with local trauma, infection and inflammation. We report a case of an intraneural and intramuscular nodular fasciitis presenting in the obturator nerve and gracilis muscle, respectively. To our knowledge, this is the second reported case of this disease presenting in a nerve of the lower extremity, as well as the first reported case of it presenting within muscle and nerve simultaneously.
We report the treatment and follow-up, including MRI, of two patients with idiopathic hypertrophic pachymeningitis and review the English language literature, with emphasis on management and outcome in this rare disorder.
Methods and Materials:
The files of two patients were reviewed, with relevant histopathology and imaging (MRI). The first patient has been followed for sixteen years (the longest MRI-documented postoperative course reported for this condition) and the second for two years. The English language literature was reviewed, including a summary of all reported patients that have been followed with MRI or CT imaging.
Despite extensive investigation, no underlying etiology was determined in either patient. Histopathological studies revealed a chronic inflammatory dural infiltrate in both patients, with granulomas in the first but not the second patient. The first patient underwent surgery twice and has remained stable for sixteen years, despite persistent neurologic deficits. The second patient was managed with dexamethasone after a surgical biopsy, and experienced complete resolution of all neurological deficits and abnormalities seen with MRI.
Although prompt and extensive surgery has been recommended for this condition, the results from our second patient indicate that complete remission can be achieved in some patients with biopsy and steroid therapy. This also supports the view that autoimmune mechanisms underlie idiopathic hypertrophic pachymeningitis. The first patient illustrates that extensive laminectomies may be an effective therapeutic option but chronic discomfort may result. If extensive surgery must be performed, laminoplasty should be done because of the potential for reduced pain and improved long-term spinal stability.
Archaeological excavations carried out during the past five years along the Pacific coast of Mexico, Guatemala, and El Salvador have recovered 79 new 14C dates for the Late Archaic and Early to Middle Formative periods. We analyze these new dates along with 25 previously published dates to refine a sequence of 10 archaeological phases spanning almost three and a half millennia, from ca. 4000 to 650 B.C. The phases are summarized with a brief description of their most salient characteristics. We include illustrations of the Early Formative period ceramics and figurines from the Mazatan region. The sequence of phases reveals a trajectory of cultural evolution beginning in the Archaic period with the mobile hunting, fishing, and gathering Chantuto people. By 1550 B.C., the first ceramic-using sedentary communities appeared on the coast of Chiapas. They were hunter-fisher-gatherers who supplemented their food supply with cultivated plants, including maize and beans. We suggest that by the Locona phase (1400–1250 B.C.) in Chiapas, they began the transition from egalitarian sociopolitical organization to simple chiefdoms, leaving behind evidence of large-scale architectural constructions, long-distance imports such as obsidian and jade, and elaborately crafted prestige goods. Also in Chiapas, during the Cherla phase (1100–1000 B.C.), ceramic and figurine styles, nearly identical to those found at San Lorenzo Tenochtitlan on the Gulf Coast, made their first appearance. Many of the local artifact styles were gradually replaced by styles that became increasingly widespread in Mesoamerica. The chronology presented here shows that these changes were roughly contemporaneous with similar ones in neighboring regions of Mesoamerica.
Emergency physician interpretation of prehospital, paramedic-acquired, electrocardiograms (ECG) is accurate judged by comparison with that of a reference cardiologist.
Twelve-lead ECGs were obtained by paramedics in the field from 150 patients with acute chest pain. The ECGs were transmitted by cellular telephone to a central location. Each ECG was assessed for evidence of acute myocardial infarction (AMI) by: 1) a third-year, emergency medicine resident (EMP-R); 2) a residency-trained, board-certified, emergency physician (EMP-RT); 3) an emergency physician board certified under the practice option (EMP-PT); and 4) a board-certified cardiologist. Agreement between each emergency physician and the cardiologist was assessed by the kappa statistic. Hospital records were reviewed for final diagnosis of each patient.
Sixteen of 150 (10.7%) patients received a hospital discharge diagnosis of AMI. Sensitivity of physician interpretation ranged from 0.31 to 0.56. All physicians achieved specificity of 0.99. False-positive rates for the physicians ranged from 0.18–0.29. The mean positive predictive value for the four physicians was 0.77±0.05; the mean negative predictive value was 0.94±0.01. The total agreements between the EMP-R, EMP-RT, and EMP-PT and the cardiologists were 0.97, 0.96, and 0.97, respectively. Kappa values for agreement between the emergency physicians and the cardiologist ranged from 0.65–0.79.
Residency-trained or board-certified emergency physician interpretations of prehospital, paramedic-acquired 12-lead ECGs show a high degree of agreement with reference cardiologist interpretations.
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