Confrontation naming does not add incremental diagnostic utility in MCI and Alzheimer's disease.

As the incidence of dementia increases, there is a growing need to determine the diagnostic utility of specific neuropsychological tests in the early diagnosis of Alzheimer's disease (AD). In this study, the relative utility of Boston Naming Test (BNT) in the diagnosis of AD was examined and compared to the diagnostic utility of other neuropsychological measures commonly used in the evaluation of AD. Individuals with AD (n = 306), Mild Cognitive Impairment (MCI; n = 67), and cognitively normal subjects (n = 409) with at least 2 annual evaluations were included. Logistic regression analysis suggested that initial BNT impairment is associated with increased risk of subsequent AD diagnosis. However, this risk is significantly less than that imparted by measures of delayed recall impairments. A multivariate Cox proportional hazards regression analysis suggested that BNT impairment imparted no additional risk for subsequent AD diagnosis after delayed recall impairments were included in the model. Although BNT impairment occurred in all severity groups, it was ubiquitous only in moderate to severe dementia. Collectively these results suggest that although BNT impairments become more common as AD progresses, they are neither necessary for the diagnosis of AD nor particularly useful in identifying early AD.     

Abnormalities of the neonatal brain: MR imaging. Part I. Intracranial hemorrhage

The authors prospectively evaluated 82 neonates, ranging in gestational age from 29 to 44 weeks postconception, with magnetic resonance (MR) imaging at 0.6 T. Twenty-two cases of hemorrhage in 15 infants were identified. Ultrasound (US) and computed tomography (CT) were superior to MR in the first few days after parenchymal hemorrhage, since at this time lesions were apparent on only T2-weighted images. After the first 3 days, MR was the single best modality because (a) hemorrhage on CT became imperceptible in the 2d week, whereas the high signal of hemorrhage on MR persisted for 2-11 weeks; (b) MR permitted rough dating of hemorrhage according to changes in signal intensity; and (c) MR was superior in identifying subdural or epidural hemorrhage. Because of the nonspecificity and restricted field of view of US and the inability of CT to depict hemorrhage after 7-10 days, the authors conclude that MR significantly improves the detection of intracranial hemorrhage in neonates.     

Abnormalities of the neonatal brain: MR imaging. Part II. Hypoxic- ischemic brain injury

Eighty-five infants, 82 of whom were 29-44 weeks postconceptional age, were imaged with a 0.6-T magnet. Eight infants had cerebral infarction. In premature neonates with very water, low-intensity white matter on T1-weighted images, ultrasound was better than both computed tomography and magnetic resonance (MR) imaging in depicting parenchymal changes of infarction or edema. However, after 37 weeks gestation, MR imaging was superior. Cerebral atrophy, present in seven infants, was consistent with subarachnoid space widths of 7 mm or more, or subarachnoid space widths of 5-6 mm with ventricular/brain ratios of 0.36 or greater. Delayed myelination was seen in a total of 18 infants with histories of hypoxic-ischemic insult. MR imaging shows promise in the neonatal period. It facilitates recognition of infarcts in full-term infants and may be used to predict abnormal neurologic outcome in infants who have initial delayed myelination.     

1H magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer's disease.

The aim of this study was to examine the associations of apolipoprotein E (APOE) genotype, metabolic changes in the posterior cingulate detected by 1H magnetic resonance spectroscopy (MRS), and neuropsychologic measures of memory and cognition both in normally aging elderly, and in patients with mild cognitive impairment (MCI) and AD. We studied 67 controls, 18 MCI and 33 AD patients. We used the Dementia Rating Scale total score (DRSTOT) as a measure of general cognitive function and the total learning from the Auditory Verbal Learning Test (AVTOT) as a measure of memory performance. No differences were noted on 1H-MRS metabolite ratios or cognitive measures across APOE genotype within control and patient groups. In controls, age was a significant predictor of both cognitive test scores, and NAA/Cr was a univariate associate of DRSTOT. All 3 1H-MRS metabolite ratios, N-acetylaspartate (NAA)/creatine (Cr), myoinositol (MI)/Cr, and NAA/MI, were univariate associates of AVTOT and DRSTOT scores in the combined MCI and AD group. In stepwise regression analyses in the combined patient group only NAA/MI entered the models. These data suggest NAA/Cr could be a modest predictor of general cognitive function in both healthy elderly and impaired patients, while MI/Cr is a more specific marker for neuropsychologic dysfunction associated with neurodegenerative disease. Among 1H-MRS measurements, the NAA/MI ratio maybe the most efficient predictor of memory and cognitive function in patients with MCI and AD.     

Mathematical modeling of platelet survival with implications for optimal transfusion practice in the chronically platelet transfusion- dependent patient

BACKGROUND: It is known that in vivo platelet survival varies as the platelet count changes. Previous attempts at curve fitting fail to predict the decreased platelet survival in thrombocythemia. Therefore, mathematical relations that more closely approximate platelet survival were derived and used in models of platelet transfusion practice. STUDY DESIGN AND METHODS: A differential equation for platelet loss was derived that included a constant (constant homeostatic loss), a first- order term (senescent loss), and a second-order term (one proportional to the square of the platelet concentration and whose contribution is expected to be significant only at higher platelet concentrations). Data derived from this model was compared to platelet survival data in normal, thrombocytopenic, and thrombocythemic patients and to the platelet decay after high-dose chemotherapy. To provide further validation of this model, predicted and actual platelet requirements were calculated or obtained (chart review) in bone marrow patients with uncomplicated thrombocytopenia after ablation and at two platelet- transfusion thresholds (20 and 10 × 10(9)/L). RESULTS: The equations accurately modeled normal, thrombocytopenic, and thrombocythemic platelet survival. Chart review demonstrated a 12.5 percent reduction in platelet transfusion requirements when the transfusion threshold was reduced from 20 to 10 × 10(9) per L. The model predicted a reduction of 14.0 percent. For 100 days of uncomplicated thrombocytopenia and a transfusion threshold of 10 × 10(9) per L, transfusion of 3 units of platelet concentrates compared to a 6-unit pool of platelet concentrates, resulted in a 22-percent savings of platelet units. CONCLUSION: Platelet survival as a function of platelet concentration can be modeled by use of a differential equation. This model challenges current dogma regarding platelet destruction and predicts decreased platelet survival in thrombocythemic patients. The model illustrates that large doses of platelets would result in greater time between transfusions, however, more units of platelets are used. Consideration should be given to the more frequent use of smaller doses of platelets in patients who chronically require platelet transfusion support.     

Gene and other biological therapies for vascular diseases

Summary— Gene transfer and antisense therapy offer novel approaches to the study and treatment of vascular diseases. The localized nature of vascular diseases like restenosis has made the application of genetic material an attractive therapeutic option. Viral and nonviral vectors have been developed to facilitate the entry of foreign DNA or RNA into cells. Vector improvement and production, demonstration of vector safety and demonstration of therapeutic efficacy are among the main present challenges. Various strategies have already been shown to be successful in preventing restenosis in animal models and include: the transfer of the herpes simplex virus thymidine kinase associated with ganciclovir; transfection of the cell cycle regulatory genes encoding for the active form of retinoblastoma gene product (Rb) or the cyclin-dependant kinase inhibitor p21, and antisense therapy. Therapeutic angiogenesis using gene transfer is a new strategy for the treatment of severe limb ischemia. Transfection of DNA encoding for the vascular endothelial growth factor has resulted in increasing collateral flow in animal models of peripheral ischemia. This approach is currently being investigated in a clinical trial in patients with distal ischemia. Other potential targets for genetic treatment in cardiovascular diseases include thrombosis, extracellular matrix synthesis and lipid metabolism.