PET network abnormalities and cognitive decline in patients with mild cognitive impairment.

Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered.     

Severe Chlamydia trachomatis pneumonia in a patient with no immune deficiency

A 40-year-old patient with no immune deficiency was admitted because of severe bilateral pneumonia and pleural effusion. The diagnosis of Chlamydia trachomatis pneumonia was confirmed by isolation of the pathogen and the appearance of serum antibodies to Chlamydia species.     

Inter- and intraindividual variability in recognition memory: effects of aging and estrogen use

Traditionally, studies of cognitive aging have focused on comparing the average performance of younger and older adults, whereas variability around the mean has been attributed to task-irrelevant noise. The present study examined the hypothesis that variability in memory performance increases with age and that estrogen helps temper age-related increases in variability. Postmenopausal estrogen users, estrogen and progestin (est + prog) users, and nonusers, as well as younger women, completed 16 blocks of an item-source memory task. Older women showed greater variability than younger women on measures of dispersion and consistency. Estrogen users, but not est + prog users, performed more consistently than nonusers. Overall, age-related increases in variability differed with the type of variability measured, and estrogen use, but not est + prog use, appeared to reduce age-related increases in at least 1 form of variability.     

Disorientation following stroke: Frequency,course, and clinical correlates

To investigate the frequency, course, and clinical correlates of disorientation following stroke, we administered the Mini-Mental State Examination orientation subtest to 177 alert patients 7–10 days and 3 months after stroke and 240 stroke-free nondemented subjects. Disorientation was defined as a score 8/10. Seventy-two (40.7%) of the patients were disoriented 7–10 days after stroke and 39 patients (22.0% of the sample) remained disoriented 3 months later. A logistic regression analysis determined that persistent disorientation was significantly related to stroke status [odds ratio (OR)=5.8], after adjusting for memory and attentional deficits and demographic variables. Among stroke patients, disorientation was associated with severe hemispheral stroke syndromes (OR=7.7), but not infarct location or vascular risk factor history, after adjusting for memory and attentional deficits and demographic variables. Sensitivity and specificity analyses determined that disorientation was an inaccurate marker for dementia or deficits in memory or attention, while intact orientation was associated with a low probability of dementia or memory dysfunction in most patients but not preserved attention. We conclude that disorientation is common and persistent following stroke and associated with severe hemispheral stroke syndromes but not infarct location. While disorientation is a poor marker for dementia or deficits in memory or attention, intact orientation should suggest that cognitive functions are likely to be preserved.Presented in part at the 118th Annual Meeting of the American Neurological Association, Boston, Massachusetts, October 1993     

Phonological dyslexia without phonological impairment?

RG, a patient with probable Alzheimer's disease, showed a severe impairment in nonword reading. RG's word reading was intact, for example, as demonstrated by her scores in standardised reading tasks, which were comparable to those of normal controls. No phonological impairment was apparent in speech production and comprehension. Moreover, RG performed well in a series of phonological tasks (e.g., production of a rhyming word, phoneme identification) on which patients with a reading deficit selective for nonwords have been reported to encounter problems. RG's data severely constrain reading models proposing that nonword reading deficits are caused by phonological deficits. However, RG's data are compatible with dual-route reading models, which do not propose a link between nonword reading deficits and phonological impairment.     

Respiratory arrest in patients undergoing arteriovenous graft placement with supraclavicular brachial plexus block: a case series

Supraclavicular brachial plexus block is commonly used for upper extremity surgery. Respiratory arrest in three patients with end-stage renal disease after ultrasound-guided supraclavicular brachial plexus block for creation of an arteriovenous graft over a 6-month period is presented. Patients with renal failure may represent a group at particular risk for respiratory failure following supraclavicular brachial plexus block.     

Protein topology determines binding mechanism

Protein recognition and binding, which result in either transient or long-lived complexes, play a fundamental role in many biological functions, but sometimes also result in pathologic aggregates. We use a simplified simulation model to survey a range of systems where two highly flexible protein chains form a homodimer. In all cases, this model, which corresponds to a perfectly funneled energy landscape for folding and binding, reproduces the macroscopic experimental observations on whether folding and binding are coupled in one step or whether intermediates occur. Owing to the minimal frustration principle, we find that, as in the case of protein folding, the native topology is the major factor that governs the choice of binding mechanism. Even when the monomer is stable on its own, binding sometimes occurs fastest through unfolded intermediates, thus showing the speedup envisioned in the fly-casting scenario for molecular recognition.     

The use of the hydrodynamic HBV animal model to study HBV biology and anti-viral therapy.

A simple reproducible and versatile small animal model for hepatitis B virus (HBV) infection is still unavailable. We have generated a simple transient liver-targeted transgenic mouse. Hydrodynamics tail vein injection of a head-to-tail dimer of adw HBV genome (pHBVadwHTD) into immunocompetent mice generated HBsAg and HBeAg expression in both serum and hepatocytes, followed by seroconversion. The injection of pHBVadwHTD into SCID mice generated prolonged HBsAg and HBeAg antigenemia and HBV viremia. Our results demonstrate that hydrodynamic injection of naked DNA could support the generation of HBV particles. We used this model for the assessment of anti-viral agents. Administration of our human monoclonal antibodies, HBV-Ab17(XTL) and HBV-Ab19(XTL), as well as Lamivudine (3TC) treatment suppressed HBV viremia. The model presented herein supports long and stable expression of HBV and will enable determination of various biological questions related to HBV life cycle, mutants and could enhance the development of anti-viral reagents.     

Reference Ability Neural Network‐selective functional connectivity across the lifespan

Previous studies have demonstrated that four latent variables, or reference abilities (RAs), can account for the majority of age‐related changes in cognition: these being episodic memory, fluid reasoning, speed of processing, and vocabulary. In the current study, we focused on RA‐selective functional connectivity patterns that vary with both age and behavior. We analyzed fMRI data from 287 community‐dwelling adults (20–80 years) on a battery of tests relating to the four RAs (three tests per RA = 12 tests). Functional connectivity values were calculated between a pre‐defined set of 264 ROIs (nodes). Across all participants, we (a) identified connections (edges) that correlated with an RA‐specific indicator variable and, indexing only these edges; (b) performed linear regression analysis per edge, regressing indicator correlations (Model 1) and connectivity values (Model 2) on Age, Behavioral Performance, and the Interaction term; and (c) took the conjunction of significant edges between models. Results revealed a different subset of edges for each RA whose connectivity strength and domain‐selectivity varied with age and behavior. Strikingly, the fluid reasoning RA was particularly vulnerable to the effects of age and displayed the most extensive connectivity and selectivity “footprint” for behavior. These findings indicate that different functional networks are recruited across RA, with fluid reasoning displaying a special status among them.