Taxonomic Interference Associated with Phonemic Paraphasias in Agrammatic Primary Progressive Aphasia.

Phonemic paraphasias are thought to reflect phonological (post-semantic) deficits in language production. Here we present evidence that phonemic paraphasias in non-semantic primary progressive aphasia (PPA) may be associated with taxonomic interference. Agrammatic and logopenic PPA patients and control participants performed a word-to-picture visual search task where they matched a stimulus noun to 1 of 16 object pictures as their eye movements were recorded. Participants were subsequently asked to name the same items. We measured taxonomic interference (ratio of time spent viewing related vs. unrelated foils) during the search task for each item. Target items that elicited a phonemic paraphasia during object naming elicited increased taxonomic interference during the search task in agrammatic but not logopenic PPA patients. These results could reflect either very subtle sub-clinical semantic distortions of word representations or partial degradation of specific phonological word forms in agrammatic PPA during both word-to-picture matching (input stage) and picture naming (output stage). The mechanism for phonemic paraphasias in logopenic patients seems to be different and to be operative at the pre-articulatory stage of phonological retrieval. Glucose metabolic imaging suggests that degeneration in the left posterior frontal lobe and left temporo-parietal junction, respectively, might underlie these different patterns of phonemic paraphasia.

Biomechanical changes and recovery of gait function after total hip arthroplasty for osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To determine the change in walking gait biomechanics after total hip arthroplasty (THA) for osteoarthritis (OA) compared to the pre-operative gait status, and to compare the recovery of gait following THA with healthy individuals. METHODS: Systematic review with meta-analysis of studies investigating changes in gait biomechanics after THA compared to (1) preoperative levels and (2) healthy individuals. Data were pooled at commonly reported time points and standardised mean differences (SMDs) were calculated in meta-analyses for spatiotemporal, kinematic and kinetic parameters. RESULTS: Seventy-four studies with a total of 2,477 patients were included. At 6 weeks postoperative, increases were evident for walking speed (SMD: 0.32, 95% confidence intervals (CI) 0.14, 0.50), stride length (SMD: 0.40, 95% CI 0.19, 0.61), step length (SMD: 0.41, 95% CI 0.23, 0.59), and transverse plane hip range of motion (ROM) (SMD: 0.36, 95% CI 0.05, 0.67) compared to pre-operative gait. Sagittal, coronal and transverse hip ROM was significantly increased at 3 months (SMDs: 0.50 to 1.07). At 12 months postoperative, patients demonstrated deficits compared with healthy individuals for walking speed (SMD: -0.59, 95% CI -1.08 to -0.11), stride length (SMD: -1.27, 95% CI -1.63, -0.91), single limb support time (SMD: -0.82, 95% CI -1.23, -0.41) and sagittal plane hip ROM (SMD: -1.16, 95% CI -1.83, -0.49). Risk of bias scores ranged from seven to 24 out of 26. CONCLUSIONS: Following THA for OA, early improvements were demonstrated for spatiotemporal and kinematic gait patterns compared to the pre-operative levels. Deficits were still observed in THA patients compared to healthy individuals at 12 months.

The eyes speak when the mouth cannot: Using eye movements to interpret omissions in primary progressive aphasia.

Though it may seem simple, object naming is a complex multistage process that can be impaired by lesions at various sites of the language network. Individuals with neurodegenerative disorders of language, known as primary progressive aphasias (PPA), have difficulty with naming objects, and instead frequently say "I don't know" or fail to give a vocal response at all, known as an omission. Whereas other types of naming errors (paraphasias) give clues as to which aspects of the language network have been compromised, the mechanisms underlying omissions remain largely unknown. In this study, we used a novel eye tracking approach to probe the cognitive mechanisms of omissions in the logopenic and semantic variants of PPA (PPA-L and PPA-S). For each participant, we identified pictures of common objects (e.g., animals, tools) that they could name aloud correctly, as well as pictures that elicited an omission. In a separate word-to-picture matching task, those pictures appeared as targets embedded among an array with 15 foils. Participants were given a verbal cue and tasked with pointing to the target, while eye movements were monitored. On trials with correctly-named targets, controls and both PPA groups ceased visual search soon after foveating the target. On omission trials, however, the PPA-S group failed to stop searching, and went on to view many foils "post-target". As further indication of impaired word knowledge, gaze of the PPA-S group was subject to excessive "taxonomic capture", such that they spent less time viewing the target and more time viewing related foils on omission trials. In contrast, viewing behavior of the PPA-L group was similar to controls on both correctly-named and omission trials. These results indicate that the mechanisms of omission in PPA differ by variant. In PPA-S, anterior temporal lobe degeneration causes taxonomic blurring, such that words from the same category can no longer be reliably distinguished. In PPA-L, word knowledge remains relatively intact, and omissions instead appear to be caused by downstream factors (e.g., lexical access, phonological encoding). These findings demonstrate that when words fail, eye movements can be particularly informative.

The structure and function of lipoxygenase.

Lipoxygenases are non-heme iron enzymes that catalyze the dioxygenation of polyunsaturated fatty acids, yielding hydroperoxides. The first crystal structures have recently been published, revealing an unusual iron site. There have also been substantial developments in the analysis of the kinetics of the reaction, including the observation of uniquely large primary deuterium isotope effects. Exploitation of these results should enable substantial progress in understanding what appears to be a complicated and fascinating chemical mechanism.

Perioperative assessment of older surgical patients using a frailty index-feasibility and association with adverse post-operative outcomes.

This study aimed to examine the feasibility of using a frailty index (FI) based on comprehensive geriatric assessment (CGA), to assess the level of frailty in older surgical patients preoperatively and to evaluate the association of FI-CGA with poorer postoperative outcomes. Two hundred and forty-six patients aged ≥70 years undergoing intermediate- to high-risk surgery in a tertiary hospital were recruited. Frailty was assessed using a 57-item FI-CGA form, with fit, intermediate frail, and frail patients defined as FI ≤0.25, >0.25 to 0.4, and >0.4, respectively. Adverse outcomes were ascertained at 30 days and 12 months post-surgery. Logistic regression models assessed the relationship between FI and adverse outcomes, adjusting for age, gender and acuity of surgery. The mean age of the participants was 79 years (standard deviation [SD] 6.5%), 52% were female, 91% were admitted from the community, 43% underwent acute surgery, and 19% were assessed as frail. The FI-CGA form was reported as being easy to apply, with a low patient refusal rate (2.2%). The majority of items were easy to rate, although inter-rater reliability was not tested. In relation to outcomes, greater frailty was associated with increased 12-month mortality (6.4%, 15.6%, and 23% for fit, intermediate frail, and frail patients respectively, P=0.01) and 12-month hospital readmissions (33.9%, 48.9%, and 60% respectively, P=0.004). There were no statistically significant differences between fit, intermediate frail, and frail groups in perioperative adverse events (17.4%, 23.3%, and 19.1% respectively, P=0.577) or 30-day postoperative complications (35.8%, 47.8%, and 46.8% respectively, P=0.183). Our findings suggest that it is feasible to use the FI-CGA to assess frailty preoperatively, and that using the FI-CGA may identify patients at high risk of adverse long-term outcomes.

A cryogenic optical feedthrough using polarization maintaining fibers.

Polarization maintaining optical fibers can be used to transmit linearly polarized light over long distances but their use in cryogenic environments has been limited by their sensitivity to temperature changes and associated mechanical stress. We investigate experimentally how thermal stresses affect the polarization maintaining fibers and model the observations with Jones matrices. We describe the design, construction, and testing of a feedthrough and fiber termination assembly that uses polarization maintaining fiber to transmit light from a 633 nm HeNe laser at room temperature to a homodyne polarization-based interferometer in a cryogenic vacuum. We report on the efficiency of the polarization maintaining properties of the feedthrough assembly. We also report that, at cryogenic temperatures, the interferometer can achieve a sensitivity of 8 × 10(-10) rad/√Hz at 0.05 Hz using this feedthrough.

Evidence that calcium acts as an intracellular messenger for adrenergic responses in human erythrocytes.

Adrenergic stimulation of membrane protein phosphorylation has been studied in human erythrocytes. The adrenergic enhancement in phosphorylation of band 2 could be mimicked by the calcium-specific ionophore A23187 in the presence of 10 micron extracellular calcium. Experiments with the potassium ionophore, valinomycin, showed that potassium efflux was not the primary effector of the response. Trifluoperazine, an inhibitor of the Ca2+-dependent regulatory protein, calmodulin, inhibited phosphorylation stimulation by either norepinephrine or the calcium ionophore. The norepinephrine response was observed in the absence of extracellular calcium, implicating Ca2+ released from cellular bound pools in mediating the response.

Preparation of a novel 13C-labelled heme protein.

Protohemin chloride 90% enriched with 13C in the terminal carbons of the 2-nd and 4-position vinyl side-chains has been synthesized. The 13C-NMR spectrum of carboxymyoglobin reconstituted with the 13C-enriched hemin revealed two signals of nearly equal intensity at 117.6 and 113.4 ppm downfield of tetramethylsilane. The inequivalence of these vinyl carbons must reflect differences in environment imposed by the protein.

Cholinergic stimulation of glucose transport in human erythrocytes.

The effects of cholinergic stimulation on glucose equilibrium exchange rate have been studied in human erythrocytes. Carbamylcholine increases in V of equilibrium exchange by 20% but has no significant effect on Km. The cholinergic effect is abolished by the muscarinic antagonist atropine or by alterations in intracellular calcium concentrations induced by the calcium ionophore A23187.

Adrenergic stimulation of membrane protein phosphorylation in human erythrocytes.

Adrenergic modification of membrane protein phosphorylation was studied in intact human erythrocytes. Micromolar norepinephrine increased 32P incorporation into Band 2 by 70%, and into Band 3 by 40%. Phosphorylation levels observed with a series of specific agonists and antagonists suggest that an alpha-adrenergic receptor is involved in this effect. The mechanism of linkage between this receptor and protein phosphorylation does not appear to involve modulation of intracellular concentrations of ATP, cyclic AMP, or cyclic GMP.

Calmodulin-dependent spectrin kinase activity in resealed human erythrocyte ghosts.

Membrane protein phosphorylation has been studied in resealed human erythrocyte ghosts by measuring the incorporation of 32P into spectrin and band 3. Norepinephrine- and Ca2+-stimulated phosphate incorporation was diminished in ghosts depleted of calmodulin. Ghosts prepared with endogenous calmodulin showed Ca2+- and norepinephrine-stimulated protein phosphorylation only when the ghosts had been resealed in the presence of (gamma-32P)ATP. Ghosts resealed with or without calmodulin in the presence of unlabeled ATP showed no net gain or loss of 32P when exposed to norepinephrine or a Ca2+-specific ionophore. These observations suggest that Ca2+ and norepinephrine stimulation of membrane protein phosphorylation is mediated by calmodulin-dependent spectrin kinase activity, and not by increased turnover of spectrin ATPase or by inhibition of phosphospectrin phosphatase.

A comparison of computed tomography and radionuclide scanning for detection of brain metastases in small cell lung cancer.

Neurologic history and examination, radionuclide brain scans (RN), and computed tomographic brain scans (CT) were performed at diagnosis and sequentially in 153 consecutive patients with small cell lung cancer (SCLC) to assess the sensitivity and accuracy of these screening methods and to determine whether the early detection of brain metastases influences survival. CT scans (sensitivity, 98%; positive predictive accuracy, 98%) were superior to RN scans (sensitivity, 71%; positive predictive accuracy, 86%) in patients with or without neurologic signs or symptoms. However, CT scans were positive in only 6% of asymptomatic patients at diagnosis and 13% of asymptomatic patients after systemic therapy. Brain metastases detected by CT scan were the sole site of extensive-stage disease in 6% of patients at diagnosis. Despite the enhanced ability of CT scans to detect asymptomatic lesions, survival after therapeutic cranial irradiation was similar for asymptomatic and symptomatic patients. The results suggest that CT brain scans should be used routinely in SCLC patients with neurologic signs or symptoms, at diagnosis (when treatment decisions are based on stage), and at six-month intervals in patients with prior brain metastases and in whom erratic follow-up is likely.

Rapid dynamic CT scanning in primary degenerative dementia and age-matched controls.

Dynamic computed tomography (CT) scanning of the brain was performed in 26 patients with primary degenerative dementia (PDD) and in 15 age-matched controls without evidence of a dementing illness. Changes in CT density values over time were obtained for 16 regions of interest (ROIs) that were carefully chosen to avoid overlap with adjacent cerebrospinal fluid (CSF), sulsi, or bone. CT density washout curves were compared between patients and controls to detect regions where blood brain barrier (BBB) permeability might be increased. Although the patients' washout curves declined more gradually than control curves in 11 of the 14 ROIs with a functioning BBB, in no case did the difference reach statistical significance. Intrarater correlation coefficients indicated good overall reliability in the selection of ROIs.

Vitamin E (tocopherols) in human cerebrospinal fluid.

Cerebrospinal fluid (CSF) and blood were obtained at the time of myelographic examinations from 40 adult, male, human subjects with no neurologic or metabolic abnormalities. Vitamin E (tocopherols) concentrations were determined by liquid chromatography. In subjects with normal concentrations of CSF protein (n = 22), the alpha- and gamma-tocopherol concentrations were 29.2 +/- 9.5 (mean +/- SD) and 6.5 +/- 3.6 nmol/L, respectively, in CSF and 26.0 +/- 8.1 and 6.0 +/- 3.6 mumol/L, respectively, in serum. The concentrations of alpha-tocopherol in CSF correlated significantly (P less than 0.001) with both total protein and albumin concentrations, suggesting that tocopherol transport into CSF is linked with that of plasma proteins. In vitro oxidation of vitamin E in CSF by the free-radical generator 2,2'-azobis-(2-amidinopropane) hydrochloride showed a measurable induction (lag) period. This is due to the presence of other antioxidants in human CSF.

Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia.

UNLABELLED: This study was undertaken in order to extend our previous finding of relative basal ganglia hypermetabolism in AIDS dementia complex (ADC) and to develop clinically useful metabolic indices of CNS involvement in HIV-seropositive (HIV+) subjects. METHODS: Twenty-one HIV+ subjects (11 with AIDS) underwent FDG-PET scanning; 12 had a follow-up scan at 6 mo and 4 had a third scan at 12 mo. Forty-three age-matched heterosexual volunteers served as controls. FDG-PET scanning was performed with arterial blood sampling, and scan data were analyzed using the Scaled Subprofile Model (SSM) with principal component analysis. RESULTS: SSM/principal component analysis of the combined (HIV+ and controls) FDG-PET dataset extracted two major disease-related metabolic components: (a) a nonspecific indicator of cerebral dysfunction, which was significantly correlated with age, cerebral atrophy and ADC stage and (b) the striatum, which was heavily weighted (relatively hypermetabolic) and appeared to provide a disease-specific measure of early CNS involvement. CONCLUSION: FDG-PET scans provide quantitative measures of abnormal functional connectivity in HIV-seropositives-with or without AIDS or ADC. These measures, which are robust across centers with respect to instrumentation, scanning technique and disease severity, appear to track the progression of CNS involvement in patients with subclinical neurologic or neuropsychologic dysfunction.

The role of sampling in vector control.

In most disease vector control programs of the world, little attention is given to sampling methodology for surveillance against importation of vectors, determination of vector distribution, vector incrimination, monitoring of entomologic risk factors, and evaluation of control. This paper discusses briefly the appropriate attractant and nonattractant collecting methods for each situation, the importance of using more than one collecting method, examples of entomologic indicators, basic sampling strategies (distribution, number, and frequency of samples), and guidelines for analysis of sampling data from vector programs.

A multidisciplinary study on bancroftian filariasis in Jakarta.

A study on bancroftian filariasis in Jakarta has indicated that one person in one year could be exposed to 223,000 bites of Culex pipens fatigans and to 1,941 infective-stage larvae of Wuchereria bancrofti. Blood surveys with 20 mm3 samples revealed a microfilaria rate of 6%. Although some cases of hydrocele (4% of 272 males examined) were found, there was little evidence of severe filarial disease in either males or females. Amongst wild-caught mosquitoes only 0.3% contained infective larvae, but much higher levels of vectorial competence were established under laboratory conditions. High daily vector mortality (30%) coupled with noticeable improvements in standards of living could have been important factors preventing an increase in endemicity.

Disposable containers as larval habitats for Aedes aegypti in a city with regular refuse collection: a study in Marília, São Paulo State, Brazil.

In Marília, Brazil, refuse is collected at least every other day, yet non-useful, non-returnable containers such as cans, plastic bottles and tires account for almost half of the container habitats found positive for the Aedes aegypti mosquito. A study was therefore conducted to investigate why these containers exist despite regular refuse collection and a high level of awareness of dengue prevention, and how the control program could most effectively respond. Differing community perceptions as to what constitutes refuse were found to lead people to store a variety of containers in their yard. Other dimensions of the problem include the presence of informal refuse collectors in search of saleable materials, and dumping of refuse in vacant lots and along roads. An intervention based on these data will involve the informal refuse collectors in implementation of a community-based recycling project.

Symptomatic intracranial pneumatocele from mastoid sinus of spontaneous origin. Case report.

A case of a large intracranial pneumatocele arising from mastoid air cells is reported. The patient became symptomatic after multiple coughing spells and required craniotomy for repair of the dural hiatus. The possible etiology of such a large spontaneous pneumatocele is discussed in the context of a review of the pertinent literature.

Infectious diseases of the brain.

Magnetic resonance imaging is the modality of choice for the characterization of intracranial inflammation, by defining ependyma, white matter, gray matter, and leptomeningeal involvement. Hemorrhage is well shown, but calcification is difficult to identify. Intravenous Gd-DTPA is useful in the evaluation of B-b barrier abnormalities. Although it is not often possible to make a specific microbiologic diagnosis, MR appearances are usually helpful in excluding other abnormalities, such as neoplasm or infarction. Knowledge of the number and size of individual lesions is invaluable in monitoring therapy.