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51.
Corey-Bloom J 《International psychogeriatrics / IPA》2002,14(Z1):51-75
Cognitive decline, commonly first recognized as memory impairment, is a typical feature of Alzheimer's disease (AD). Neuropathological changes in the cerebral cortex and limbic system lead to deficits in learning, memory, language, and visuospatial skills. The precise nature of cognitive dysfunction reflects the distribution of pathological changes in AD. These will vary along the disease severity continuum and may also depend on where the disease sits in the spectrum of dementia. For example, AD-related disorders such as Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) also show symptoms of cognitive decline and share several pathological features, including degeneration of cortical cholinergic and striatal dopaminergic neurons. In vascular dementia (VaD), there is often an unequal distribution of cognitive deficit, with severe impairment in some functions and relative sparing of others. Cholinesterase (ChE) inhibitors, which help restore acetylcholine levels in the brain, are licensed for the symptomatic treatment of AD and have shown additional benefit in related dementias. Physiological correlates of cholinergic function/dysfunction in the brain include regional cerebral blood flow, glucose metabolism, and cerebrospinal fluid levels of ChE enzymes. These variables represent valuable markers of the clinical efficacy of ChE inhibitors. However, direct assessment of cognitive improvement, stabilization or decline is usually considered the key efficacy parameter in clinical studies of ChE inhibitors in AD and related dementias. Large-scale, placebo-controlled clinical studies of ChE inhibitors have demonstrated efficacy in treating the cognitive impairments associated with AD. Randomized comparative studies of ChE inhibitors are now under way to directly compare symptomatic efficacy and effects on disease progression. Clinical trial data of the cognitive effects of ChE inhibitors in AD, LBD, PDD, and VaD are discussed in detail in this article. The benefits of long-term treatment on symptomatic improvement in cognition and further potential disease-modifying effects are highlighted. 相似文献
52.
Cepeda C Crawford CA Margulies JE Watson JB Levine MS Cohen RW 《Developmental neuroscience》2002,24(4):262-271
Our laboratory has been studying the spastic Han-Wistar (sHW) rat as a model of neuronal degeneration. Mutant sHW rats display a number of developmental abnormalities that eventually lead to hippocampal pyramidal cell death and synaptic reorganization starting around 30 days of age. The present study examined the contribution of hippocampal reorganization to the expression of seizures induced by systemic injections of kainic acid. Behavioral observations, EEG recordings and hippocampal Fos protein expression in these animals indicated that mutants develop paroxysmal discharges and seizures earlier than controls and the intensity of epileptic manifestations is greater. Kainate injections were lethal in 50% of mutants compared to only 5% of controls. Fos expression was increased approximately twofold in the mutant hippocampus, implicating abnormal excitation in this region. Additional studies in untreated animals indicated that GluR2 mRNA expression was significantly increased throughout the hippocampus in mutant animals, possibly contributing to the enhanced susceptibility to kainate treatment. These results confirm the role of synaptic reorganization in the increased propensity to develop epileptic discharges. Our data also underscore the usefulness of this natural model of cell degeneration and reactive synaptogenesis for understanding the mechanisms of neuronal hyperexcitability. 相似文献
53.
Jody S. Lee M.D. Amar Galla M.D. Robert L. Shaw B.Sc. F.R.C.S. F.R.C.R. John H. Harris Jr. M.D. D.Sc. F.A.C.R. 《Emergency radiology》1995,2(2):77-83
The posteroanterior and lateral wrist radiographs of 52 adults who sustained acute distal radial fractures were reviewed to
determine the incidence of radiographic signs of concomitant acute scapholunate ligamentous injury. Three radiographic criteria,
either separately or in concert, were used to identify scapholunate ligamentous injury. They are (a) scapholunate angle >60°;
(b) widening of the scapholunate space >2 mm; and (c) the cortical ring sign (also called the scaphoid or signet ring sign).
Thirty-six of 52 cases (69%; 95% confidence interval =52.1–82.2%) showed evidence of scapholunate ligamentous injury; 16 of
52 cases (31%; 95% confidence interval =16.8–46.6%) showed no evidence of scapholunate ligamentous injury. Statistical analysis
suggests that a minimum of 52.1% of all adult distal radial fractures are associated with signs of concurrent acute scapholunate
ligamentous injury. The analysis also suggests that independent variables such as age, gender, severity of radius fracture,
or mechanism of injury do not significantly alter the incidence of associated carpal ligamentous instability.
This study has established a greater than 52.1% incidence of radiographic signs of scapholunate instability in adults with
acute distal radial fractures. It is incumbent upon radiologists to search for the signs of scapholunate dissociation in all
adult cases of distal radius fracture, regardless of age, gender, severity of radius fracture, or mechanism of injury. 相似文献
54.
BACKGROUND: Starting a surgical internship is a stressful experience. We developed a web and simulation-based curriculum to ease this transition. METHODS: We created an educational website containing a curriculum of commonly encountered on call situations. After match day in 2003, we contacted all of our new surgical interns. We performed a confidence assessment using a Likert-scale questionnaire, and the trainees were given access to the curriculum. In June 2003, we performed human patient simulator sessions. The participants were asked to provide feedback regarding the simulator experience. During the first week of residency, they were again asked to answer the confidence questionnaire. RESULTS: Sixteen residents (94%) used the web curriculum, and 17 (100%) participated in the simulations. Eleven (65%) filled out both questionnaires. The confidence score improved from 5.4 to 6.7 (P < .0001). CONCLUSIONS: A web and simulation-based curriculum for incoming house staff is feasible. Studies are underway to validate this novel method and to expand its use for surgical education. 相似文献
55.
Heerema-McKenney A Harrison MR Bratton B Farrell J Zaloudek C 《The American journal of surgical pathology》2005,29(1):29-38
Extragonadal teratoma is the most common congenital tumor. The prognostic significance of the grade of immaturity and the presence of small foci of conventional yolk sac tumor (YST) in fetal and neonatal teratomas have not been determined. We report detailed histologic studies of 22 congenital teratomas, including eight tumors resected in utero for developing hydrops, and correlate the histologic features with initial serum alpha-fetoprotein (AFP) levels and clinical outcome. All fetal tumors that required in utero intervention were grade 3 immature teratomas, with admixed conventional YST in 44%. Among tumors resected postnatally, those presenting in utero were more commonly immature (71% vs. 50%). All initial post-surgical serum AFP levels were high, as expected in a neonate. No correlation was found between AFP elevation above the mean for gestational age and the presence of YST, hepatic differentiation, or immature endodermal glands in the tumor. Among 15 survivors with follow-up, 5 patients had malignant mixed germ cell tumors (immature teratoma with foci of conventional YST) and 5 had immature teratomas with foci of hepatic differentiation or immature endodermal glands with subnuclear vacuoles (so-called "well-differentiated YST"). No patient has developed recurrent or metastatic disease after treatment by complete surgical excision alone (mean follow-up, 37.6 months). The clinical behavior of congenital teratomas is determined predominantly by whether or not the tumor can be completely resected and in our study did not correlate with the grade of the teratoma or with the presence or absence of foci of hepatic tissue, immature intestinal glands, or foci of conventional YST. 相似文献
56.
57.
Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations 总被引:6,自引:0,他引:6
Hersh CP Demeo DL Lange C Litonjua AA Reilly JJ Kwiatkowski D Laird N Sylvia JS Sparrow D Speizer FE Weiss ST Silverman EK 《American journal of respiratory cell and molecular biology》2005,33(1):71-78
Case-control studies have successfully identified many significant genetic associations for complex diseases, but lack of replication has been a criticism of case-control genetic association studies in general. We selected 12 candidate genes with reported associations to chronic obstructive pulmonary disease (COPD) and genotyped 29 polymorphisms in a family-based study and in a case-control study. In the Boston Early-Onset COPD Study families, significant associations with quantitative and/or qualitative COPD-related phenotypes were found for the tumor necrosis factor (TNF)-alpha -308G>A promoter polymorphism (P < 0.02), a coding variant in surfactant protein B (SFTPB Thr131Ile) (P = 0.03), and the (GT)(31) allele of the heme oxygenase (HMOX1) promoter short tandem repeat (P = 0.02). In the case-control study, the SFTPB Thr131Ile polymorphism was associated with COPD, but only in the presence of a gene-by-environment interaction term (P = 0.01 for both main effect and interaction). The 30-repeat, but not the 31-repeat, allele of HMOX1 was associated (P = 0.04). The TNF -308G>A polymorphism was not significant. In addition, the microsomal epoxide hydrolase "fast" allele (EPHX1 His139Arg) was significantly associated in the case-control study (P = 0.03). Although some evidence for replication was found for SFTPB and HMOX1, none of the previously published COPD genetic associations was convincingly replicated across both study designs. 相似文献
58.
59.
Freedman R Ross R Leonard S Myles-Worsley M Adams CE Waldo M Tregellas J Martin L Olincy A Tanabe J Kisley MA Hunter S Stevens KE 《Dialogues in clinical neuroscience》2005,7(1):17-29
Biological traits that are predictive of the later development of psychosis have not yet been identified. The complex, multidetermined nature of schizophrenia and other psychoses makes it unlikely that any single biomarker will be both sensitive and specific enough to unambiguously identify individuals who will later become psychotic. However, current genetic research has begun to identify genes associated with schizophrenia, some of which have phenotypes that appear early in life. While these phenotypes have low predictive power for identifying individuals who will become psychotic, they do serve as biomarkers for pathophysiological processes that can become the targets of prevention strategies. Examples are given from work on the role of the alpha(T)nicotinic receptor and its gene CHRNA7 on chromosome 15 in the neurobiology and genetic transmission of schizophrenia. 相似文献
60.
Recall discriminability: utility of a new CVLT-II measure in the differential diagnosis of dementia.
Dean C Delis Spencer R Wetter Mark W Jacobson Guerry Peavy Joanne Hamilton Assawin Gongvatana Joel H Kramer Mark W Bondi Jody Corey-Bloom David P Salmon 《Journal of the International Neuropsychological Society》2005,11(6):708-715
Memory tests that are in a recall format have almost universally measured accuracy in terms of the number of target items reported by the examinee. However, this traditional scoring method can, in certain cases, result in artificially inflated memory accuracy scores. That is, just as a "yes" response bias and high false-positive rate on recognition testing can artificially inflate a patient's hit rate, so, too, a liberal response bias and high intrusion rate on recall testing can artificially inflate a patient's level of target recall. Recognition tests correct for this problem by using a discriminability measure that provides a single score of hit rate relative to false-positive rate; however, recall tests rarely provide a single score of recall accuracy that corrects for intrusion rate. In the present study, we examined the utility of a new recall discriminability measure that analyzes target recall relative to intrusion rate. Patients with Alzheimer's disease (AD) or Huntington's disease (HD) were administered the CVLT-II, which provides both the traditional measure of target recall and a new measure of recall discriminability. The results indicate that the new recall discriminability measure was superior to the traditional level of target recall measure in distinguishing the recall performance of AD and HD patients. Implications of these results for clinical practice and theories of memory disorder in dementia are discussed. 相似文献