Cognitive approaches to recovery and rehabilitation in aphasia.
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Biomedical subjects
Publications and source records attributed to N Martin.
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This study investigates the changes in auditory-verbal short-term memory (AVSTM) and error patterns in repetition observed in a Wernicke's aphasic, NC, over a period of about 2 years following the onset of a left middle cerebral artery aneurysm. When first tested, NC demonstrated deep dysphasia, a disorder characterized by the production of semantic errors in repetition and a severe disability in repeating nonwords. At this stage, his AVSTM span, assessed in a pointing task, was less than one item. As NC recovered somewhat, his performance on AVSTM tasks improved (span increased to two items), and his pattern of error in word repetition changed (fewer semantic errors, more formal paraphasias and neologisms). Other features of his span performance after some recovery resembled patterns associated with STM-based repetition impairments (reduced recency effects and reduced word length effects). In a series of computer simulation and empirical studies, we show that NC's repetition performance can be accounted for by varying two parameters of an interactive activation model of repetition adapted from Dell and O'Seaghdha's (1991) model of production: decay rate and temporal interval. These results provide support for the view that AVSTM performance depends on storage capacities intrinsic to the language processing system. Such a model allows deep dysphasia and STM-based repetition disorders to be seen as quantitative variants of the same underlying disturbance.
In models of word retrieval, it is common to differentiate lexical-semantic (word meaning) and lexical-phonological (word form) levels. There has been considerable interest in the relationship between these two levels. The so-called discrete two-stage model claims that phonological activation follows selection at the lexical-semantic level and is limited only to the selected item. In contrast, nondiscrete (interactive and cascade) models assume that all activated lexical-semantic candidates are also phonologically activated to some extent. We addressed this issue by studying an anomic patient who suffered from a partial functional disconnection between lexical-semantic and lexical-phonological levels. A multitarget repeated naming task with phonological training was employed. Systematic manipulation of semantic and phonological relatedness between the to-be-named items indicated that our patient's word error patterns were sensitive to both types of lexical relatedness. A delayed repetition task employing the same items failed to show similar effects, suggesting that they were specific to naming. The discrete two-stage model is unable to explain the observed effects of semantic and phonological relatedness. However, they are consistent with assumptions of nondiscrete models of lexical retrieval. In addition to the theoretical implications of this study, the observed effects of lexical context on word retrieval have implications for treatment of anomia.
A failed embolisation of a spinal dural arteriovenous fistula (AVF), because a pedicular injection has not reached the initial venous compartment, must be identified immediately, to allow prompt surgery and thus avoid clinical deterioration. The purpose of our study was to determine the role of CT in confirming a complete cure just after embolisation with N-butyl cyanoacrylate (NBCA). Seven patients embolised for spinal dural AVFs with perimedullary venous drainage had an immediate postembolisation CT scan. In six patients a complete cure was achieved, with a normal postembolisation angiogram in five cases. Just after injection of NBCA, we were unable to determine on plain films whether or not the glue had reached the draining vein in six of seven cases. The postembolisation CT showed various patterns: in two cured patients, the glue was visible in the inner surface of the dura mater and therefore on the venous side. In five cases, the glue was approaching the dura mater around the cord or seemed to reach its surface: in the four patients cured, the glue column was 7-18 mm high, whereas it was less than 2 mm high in the patient with angiographic proof of recurrent fistula. The follow-up angiogram remains the only way to confirm a durable cure. We suggest that immediate postembolisation CT may help in assessing endovascular treatment of spinal dural AVFs.
High resolution evoked potentials (EPs), sampled from 115 channels and spatially sharpened with the finite element deblurring method, were recorded from 8 subjects during working memory (WM) and control tasks. The tasks required matching each stimulus with a preceding stimulus on either verbal or spatial attributes. All stimuli elicited a central P200 potential that was larger in the spatial tasks than in the verbal tasks, and larger in the WM tasks than in the control tasks. Frequent, non-matching stimuli elicited a frontal, positive peak at 305 msec that was larger in the spatial WM task relative to the other tasks. Irrespective of whether subjects attended to verbal or spatial stimulus attributes, non-matching stimuli in the WM tasks also elicited an enhanced P450 potential over the left frontal cortex, followed by a sustained potential over the superior parietal cortex. A posterior P390 potential elicited by infrequent, matching stimuli was smaller in amplitude for both spatial and verbal WM tasks compared to control tasks, as was a central prestimulus CNV. These results indicate that WM is a function of a distributed system with both task-specific and task-independent components. Lesion studies and course temporal resolution functional imaging methods, such as PET and fMRI, tend to paint a fairly static picture of the cortical regions which participate in the performance of WM tasks. In contrast, the fine-grain time resolution provided by imaging brain function with EP methods provides a dynamic picture of subsecond changes in the spatial distribution of WM effects over the course of individual trials, as well as evidence for differences in the activity elicited by matching and non-matching stimuli within sequences of trials. This information about the temporal dynamics of WM provides a critical complement to the fine-grain spatial resolution provided by other imaging modalities.
Cytoplasmic desmosomes (CD) are classically found in dyskeratotic cells of many epithelial tumors. Their significance and mechanism of formation remain largely speculative. Recently, we have reported the induction of these structures in rat keratinocytes following a brief treatment with acrylamide, and proposed that protein kinase inhibition may be implicated in their formation. In the present study, we show that protein kinase inhibitor H-7 in the presence of EGF is able to induce CD in rat keratinocytes within half an hour. In serum free medium containing 20 ng/ml of EGF, desmosomal structures at different stages of assembly were obtained using H-7 at concentrations ranging between 20 and 80 microM. No such structures were found at lower concentrations. The plaque diameters were significantly small in comparison with plasma membrane plaques. EGF induced plakoglobin positive membrane invaginations and in the presence of H-7, desmosomal plaques assembled on these membranes as either half desmosomes or as symmetric ones. The present results implicate protein kinase inhibition in CD formation and suggest that EGF provides tubular membrane structures in the cytoplasm on which desmosomes may assemble.
Impairment of pulmonary diffusion is recognized following heart transplantation. This study was undertaken to determine the histopathological basis for the defect in pulmonary physiology. Heart transplant recipients (HTR) entered into a prospective study of post-transplant pulmonary physiology were asked to undergo bronchoscopy, bronchoalveolar lavage (BAL) and transbronchial biopsy (n = 18) in the presence of impaired gas transfer. Transbronchial biopsies were examined under light microscopy and demonstrated focal interstitial fibrosis in 12 patients, cytomegalovirus disease in four patients and Pneumocystis carinii pneumonia in three patients. Bronchoalveolar lavage differential counts were normal in HTR but BAL macrophages contained haemosiderin. The histological features of interstitial fibrosis may underlie the fall in gas transfer seen following heart transplantation. The presence of haemosiderin-laden macrophages late following heart transplantation suggests a capillary leak syndrome.
This paper reviews four economic studies of aspects of earnings and schooling conducted by the authors using data from the Australian Twin Register. First, estimates of the economic returns to schooling made using fixed effects and selection effects regression models incorporating an instrumental variables approach to correct for measurement error in self-reported schooling levels are examined. The finding is that up to 30 per cent of the estimated return to schooling may be due to family effects and the remainder to pure educational effects. Second, comparisons are made between the economic model of Ashenfelter and Krueger (1994) and that of DeFries and Fulker (1985) and the results obtained from each are shown to be similar. Third, gender differences in returns to schooling are estimated and family effects are found to be a more important influence in the case of males. Fourth, the influence of family effects on educational attainments is considered and it is found that around one-half of educational attainment is accounted for by genetic inheritance and up to another quarter due to shared environment effects.
Steroid sulphatase (STS) is an important enzyme in steroid metabolism. The human STS gene has been cloned and mapped to Xp22.3, proximal to the pseudoautosomal region (PAR). Using quantitative differences in STS activity among various mouse strains, a segregation pattern consistent with autosomal linkage was first reported, but more recent studies have linked Sts to the mouse PAR. Failed attempts to clone the mouse Sts gene using human reagants (STS cDNA and anti-STS antibodies) suggest a substantial divergence between these genes. However, partial amino-terminal sequence from purified rat liver Sts is very similar to its human counterpart, and several domains are conserved among all the sulphatases. We followed a degenerate-primer reverse transcriptase-PCR (RT-PCR) approach to amplify a conserved fragment of the rat Sts cDNA that was then used to clone the mouse Sts cDNA. This 2.3-kb cDNA revealed 75% similarity with rat Sts cDNA, while it was only 63% similar to human STS cDNA. Transfection of STS(-) A9 cells with the mouse Sts cDNA restored STS enzymatic activity. Sts was also mapped physically to the distal end of the mouse sex chromosomes, and our backcross studies placed Sts distal to the 'obligatory' cross-over in male meiosis.
Nontuberculous mycobacterial meningitis (NTMM) is still a rare disease despite the increase in the number of cases of disseminated mycobacterial infection related to the AIDS epidemic. Moreover, there are doubts as to the clinical relevance of the isolation of mycobacteria other than Mycobacterium tuberculosis from cerebrospinal fluid. After analyzing the clinical and pathological data, we classified the cases of NTMM into three groups: definitive (28 cases), probable (19), and doubtful (5). We found that Mycobacterium avium is the most commonly isolated species (60% of cases). M. avium meningitis presents as a disseminated disease, is usually related to serious underlying conditions (mainly immunosuppression), and is associated with a death rate that approaches 70%. Mycobacterium fortuitum meningitis is associated with previous neurosurgery or back trauma; the prognosis for this infection is better when the concomitant abscesses are drained. The clinical characteristics of Mycobacterium kansasii meningitis are similar to those of M. tuberculosis meningitis, but the mortality related to M. kansasii meningitis is high despite appropriate antibiotic treatment. Herein, we present two cases of NTMM that occurred at our center, and we review 50 additional cases reported in the English-language literature.
Incidence rates of cancers of childhood in Thailand are presented for the first time, and compared with results from cancer registries in Asia, Europe and the USA. As elsewhere in the world, leukaemia (principally acute lymphocytic), brain tumours and lymphomas comprise two-thirds of all childhood neoplasms. Carcinomas are rare, but the principal sites (liver, nasopharynx, thyroid and salivary gland) are extremely unusual elsewhere. Several features of the cancer pattern correspond to that in other Asian populations (China, Japan, Philippines), in particular the low incidence of Hodgkin's disease, Wilms' tumour and Ewing's sarcoma. Conversely, Burkitt's lymphoma is more common than elsewhere, although this may represent increasing awareness of this diagnosis amongst clinicians in recent years.
Research on malingering that involves analog methods is frequently criticized for using normal subjects Critics have suggested that analog subjects probably perform differently from clinical Malingerers because of the absence of an identifiable incentive for analog malingerers, and because analog subjects have no opportunity to gain knowledge about the disorder to be malingered In contrast, clinical malingerers have an obvious incentive and may have at least a basic knowledge of the characteristics of the disorder they are feigning In this study, psychology graduate students and faculty were asked to malinger a memory deficit on several brief neuropsychological instruments on the premise that malingering would be difficult to detect in this population because of their supposed sophistication Results indicated that in sophisticated subjects, malingering was relatively easy to detect using indices of pattern of performance on standardized neuropsychological instruments, but more difficult to detect using instruments designed to detect malingering based on probability theory, and on specified knowledge of the effects of brain damage.
Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for < or = 56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients (66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2',5' -oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.
The prognostic significance of ventricular tachyarrhythmias induced by programmed ventricular stimulation was evaluated in 492 consecutive survivors of acute myocardial infarction (AMI). Holter monitoring, signal-averaged electrocardiogram (ECG) and measurement of left ventricular ejection fraction (EF) were also performed. The protocol used up to 3 extrastimuli. Sustained monomorphic ventricular tachycardia (VT) < 270 beats/min, > 270 beats/min (ventricular flutter) (VFI), and ventricular fibrillation (VF) were induced in 99, 66 and 52 patients, respectively. Long term follow-up (mean 3.7 +/- 2.2 years) showed that most episodes of VT occurred during the first months following AMI (n = 14), but some patients (n = 6) could develop VT as late as 4 years after AMI. Sudden death (SD) (n = 22) always occurred during the first year following AMI. Multivariate analysis demonstrated that EF < 30% and induction of a VT < 270 beats/min were the only predictors for total cardiac death (P < 0.001). EF < 30%, induction of a VT < 270 beats/min and also of VFI (P < 0.05) were predictors for VT and SD: the risk was 4% in patients without inducible VT, 12% in those with inducible VF1, and 21% in those with inducible VT < 270 beats/min. In conclusion, induction of a sustained monomorphic VT < 270 beats/min or > 270 beats/min is a predictor of arrhythmic events during the first year as well as 4 years after myocardial infarction. However the risk of arrhythmic sudden death decreases after the first year, while the risk of VT persists. Because of the low positive predictive value of programmed stimulation (respectively 21% and 12% for the induction of a sustained VT and VFI), we recommended the indication of programmed stimulation in only the patients with one abnormal non-invasive investigation.
Mitochondrial RNase P RNA (Rpm1r) is coded by the RPM1 gene of mitochondrial DNA in many yeasts. As an initial step to developing a genetic approach to the structure and biogenesis of yeast mitochondrial RNase P, biolistic transformation has been used to introduce wild type and altered RPM1 genes into strains containing no mitochondrial DNA. The introduced wild type gene does support RNase P activity demonstrating that pre-existing RNase P activity is not necessary for the biosynthesis of the enzyme. Mutations introduced into RPM1 in vitro result in reduced accumulation of mature tRNA and in an alteration of the processing of Rpm1r in vivo.
Numerous reports in the literature suggest that hormones may transfer from one fetus to another, in humans as in animals. In a large sample of over seven thousand Australian adult twins, it was found that opposite-sex females showed a statistically significant tendency to hold more masculine attitudes than did same-sex female twins. This may be due to post-natal social interaction, but could also be caused by the transfer of testosterone from the male to the female fetus in opposite-sex twins.
Experimental traumatic brain injury produces a series of cellular events contributing to a neurochemical and neurometabolic cascade. This cascade is defined by the release of neurotransmitters resulting in a massive ionic flux, which, consequently, produces an increase in glycolysis. This increase in glycolysis is followed by a metabolic diaschisis, which is related to the degree and extent of behavioral deficits. Clinical efforts have now determined that a similar cascade occurs in human head injury, validating the animal model as well as providing new assessment strategies for the management and treatment of brain injury.
We describe a case of propylene glycol toxicity due to intravenous administration of etomidate for cerebral protection. A continuous etomidate infusion was titrated to burst suppression of the electroencephalogram during surgical resection of a large intracranial arteriovenous malformation. The etomidate formulation used (Amidate, Abbot) contains etomidate 2 mg/ml in a 35% propylene glycol vehicle. A total of 5 g/kg of the solvent was given during 12 h. Adverse effects of propylene glycol were observed including hyperosmolality with an increased osmolal gap, hemolysis, hemoglobinuria, and metabolic acidosis. Normalization of these metabolic and ionic alterations occurred after 12 h of discontinuation of the infusion. The potential toxicity of the solvent should be considered during long-term administration of etomidate.