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Michael Alexander

Publications and source records attributed to Michael Alexander.

18 recordsLinked to original sources
PubMed2007

Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.

Aged↗
PubMed2006

Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients.

We studied motor representation in well-recovered stroke patients. Eighteen right-handed stroke patients and eleven age-matched control subjects underwent functional Magnetic Resonance Imaging (fMRI) while performing unimanual index finger (abduction-adduction) and wrist movements (flexion-extension) using their recovered and non-affected hand. A subset of these patients underwent Transcranial Magnetic Stimulation (TMS) to elicit motor evoked potentials (MEP) in the first dorsal interosseous muscle of both hands. Imaging results suggest that good recovery utilizes both ipsi- and contralesional resources, although results differ for wrist and index finger movements. Wrist movements of the recovered arm resulted in significantly greater activation of the contralateral (lesional) and ipsilateral (contralesional) primary sensorimotor cortex (SM1), while comparing patients to control subjects performing the same task. In contrast, recovered index finger movements recruited a larger motor network, including the contralateral SM1, Supplementary Motor Area (SMA) and cerebellum when patients were compared to control subjects. TMS of the lesional hemisphere but not of the contralesional hemisphere induced MEPs in the recovered hand. TMS parameters also revealed greater transcallosal inhibition, from the contralesional to the lesional hemisphere than in the reverse direction. Disinhibition of the contralesional hemisphere observed in a subgroup of our patients suggests persistent alterations in intracortical and transcallosal (interhemispheric) interactions, despite complete functional recovery.

Adult↗
PubMed2006

Pancreatoblastoma in an adult: case report and review of the literature.

A 50-year-old man presented with progressive gastrointestinal symptoms. An abdominal computed tomography scan demonstrated a 12 x 12-cm pancreatic mass involving the greater curvature of the stomach and multiple hypervascular hepatic metastases. An initial fine needle aspiration of the pancreatic mass was nondiagnostic, and a subsequent fine needle aspiration of a liver mass was read as metastatic acinar cell carcinoma. The patient underwent a palliative resection for tumor-associated pain and gastrointestinal hemorrhage that revealed a large pancreatic tumor invading through the full thickness of the colon at the splenic flexure and adherent to the posterior gastric wall. The pathology from the distal pancreatectomy, splenectomy, partial gastrectomy, partial colectomy, and cholecystectomy unexpectedly supported a diagnosis of pancreatoblastoma with evidence for squamoid corpuscles as well as areas of acinar formation. Despite multiple chemotherapy regimens, the patient's disease continued to progress in the liver and the lungs. During the course of his therapy, the patient's serum alpha-fetoprotein levels and serum lipase levels rose concurrently, suggesting tumor-associated production of both of these factors. Seventeen months after the diagnosis of metastatic pancreatoblastoma, the patient died from his disease. Our case illustrates the fact that pancreatoblastomas are extremely difficult to diagnosis preoperatively. In addition, our case demonstrates that pancreatoblastomas can be alpha-fetoprotein producing, hormone producing, and enzyme producing when it occurs in adults.

Abdominal Pain↗
PubMed2005

Biochemical characterization of the diaphanous autoregulatory interaction in the formin homology protein FHOD1.

Diaphanous related formins (DRFs) are cytoskeleton remodeling proteins that mediate specific upstream GTPase signals to regulate cellular processes such as cytokinesis, cell polarity, and organelle motility. Previous work on the Rho-interacting DRF mDia has established that the biological activity of DRFs is regulated by an autoinhibitory interaction of a C-terminal diaphanous autoregulatory domain (DAD) with the DRF N terminus. This autoinhibition is released upon competitive binding of an activated GTPase to the N terminus of the DRF. Analyzing autoregulation of the Rac1-interacting DRF FHOD1, we utilized in vitro binding studies to identify a 60-amino acid DAD at the protein C terminus that recognizes an N-terminal formin homology (FH) 3 domain. Importantly, the FH3 domain of FHOD1 does not overlap with the proposed Rac1-binding domain. The FHOD1 DAD was found to contain one functional hydrophobic autoregulatory motif, while a previously uncharacterized basic cluster that is conserved in all DRF family DADs also contributed to the FH3-DAD interaction. Simultaneous mutation of both motifs efficiently released autoinhibition of FHOD1 in NIH3T3 cells resulting in the formation of actin stress fibers and increased serum response element transcription. A second putative hydrophobic autoregulatory motif N-terminal of the DAD belongs to a unique FHOD subdomain of yet undefined function. NMR structural analysis and size exclusion chromatography experiments revealed that the FHOD1 DAD is intrinsically unstructured with a tendency for a helical conformation in the hydrophobic autoregulation motif. Together, these data suggest that in FHOD1, DAD acts as signal sequence for binding to the well folded and monomeric FH3 domain and imply an activation mechanism that differs from competitive binding of Rac1 and DAD to one interaction site.

Amino Acid Motifs↗
PubMed2005

The reliability, validity, and preliminary responsiveness of the Eye Allergy Patient Impact Questionnaire (EAPIQ).

BACKGROUND: The Eye Allergy Patient Impact Questionnaire (EAPIQ) was developed based on a pilot study conducted in the US and focus groups with eye allergy sufferers in Europe. The purpose of this study was to present the results of the psychometric validation of the EAPIQ. METHODS: One hundred forty six patients from two allergy clinics completed the EAPIQ twice over a two-week period during the fall and winter allergy seasons, along with concurrent measures of health status, work productivity, and utility. Construct validity, reliability (internal consistency and test-retest), concurrent, known-group, and clinical validities, and responsiveness of the EAPIQ were assessed. Known-group validity was assessed by comparing EAPIQ scale scores between patients grouped according to their self-rating of ocular allergy severity (no symptoms, very mild, mild, moderate, severe, very severe). Clinical validity was assessed by assessing differences in EAPIQ scores between groups of patients rated by their clinician as non-symptomatic, mild, moderate, and severe. RESULTS AND DISCUSSION: Results from the validation study suggested the deletion of 14 of 43 items (including embedded questions) that required patients to complete the percentage of time they were troubled by something (daily activity limitations/emotional troubles). These items yielded a significant amount of missing or inconsistent data (50%). The resulting factor analysis suggested four domains: symptoms, daily life impact, psychosocial impact, and treatment satisfaction. When included as separate scales, the symptom-bother and symptom-frequency scales were highly correlated (> 0.9). As a consequence, and due to superior discriminative validity, the symptom bother and frequency items were summed. All items met the tests for item convergent validity (item-scale correlation = 0.4). The success rate for item discriminant validity testing was 97% (item-scale correlation greater with own scale than with any other). The criterion for internal consistency reliability (alpha coefficient > or = 0.70) was met for all EAPIQ scales (range 0.89-0.93), as was the criterion for test-retest reliability (intraclass correlation [ICC] > or = 0.70). Largely moderate correlations between the scales of the EAPIQ and the mini Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ) and low correlations with the Health Utilities Index 2/3 (HUI2/3) were indicative of satisfactory concurrent validity. The EAPIQ symptoms, Daily Life Impact, and Psychosocial Impact scales were able to distinguish between patients differing in eye allergy symptom severity, as rated by patients and clinicians, providing evidence of satisfactory known-group and clinical validities, respectively. Preliminary analyses indicated the EAPIQ Symptoms, Daily Life Impact, and Psychosocial Impact scales to be responsive to changes in eye allergies. CONCLUSION: Following item reduction, construct validity, reliability, concurrent validity, known-group validity, and preliminary responsiveness were satisfactory for the EAPIQ in this population of ocular allergy patients.

Adult↗
PubMed2004

Use of Sniff nasal-inspiratory force to predict survival in amyotrophic lateral sclerosis.

Respiratory muscle weakness is the usual cause of death in amyotrophic lateral sclerosis. The prognostic value of the forced vital capacity (FVC), mouth-inspiratory force, and sniff nasal-inspiratory force were established in a group of 98 patients with amyotrophic lateral sclerosis who were followed trimonthly for 3 years. Sniff nasal-inspiratory force correlated with the transdiaphragmatic pressure (r = 0.9, p < 0.01). Sniff nasal-inspiratory force was most likely to be recorded at the last visit (96% of cases), compared with either the FVC or mouth-inspiratory force (86% and 81%, respectively, p < 0.01). A sniff nasal-inspiratory force less than 40 cm H(2)O was significantly related with nocturnal hypoxemia. When sniff nasal-inspiratory force was less than 40 cm H(2)O, the hazard ratio for death was 9.1 (p = 0.001), and the median survival was 6 +/- 0.3 months. The sensitivity of FVC < 50% for predicting 6-month mortality was 58% with a specificity of 96%, whereas sniff nasal-inspiratory force less than 40 H(2)O had a sensitivity of 97% and a specificity of 79% for death within 6 months. Thus the sniff nasal-inspiratory force test is a good measure of respiratory muscle strength in amyotrophic lateral sclerosis, it can be performed by patients with advanced disease, and it gives prognostic information.

Adult↗
PubMed2004

Oropharyngeal dysphagia in amyotrophic lateral sclerosis: neurological and dysphagia specific rating scales.

BACKGROUND: Oropharyngeal dysphagia is highly prevalent in amyotrophic lateral sclerosis (ALS). Patients with dysphagia and weight loss are frequently offered gastrostomy. Although the neurological basis of dysphagia in ALS is complex, there are currently no specifically validated scales for dysphagia in ALS, and the reliability of existing generic scales has not been assessed. METHODS: We undertook a prospective study of 25 patients who fulfilled the criteria for definite or probable ALS. We examined the reliability of the Dysphagia Outcome Severity Scale (DOSS) and the Aspiration-Penetration Rating Scale (APRS) and the correlation between these scales and the Norris ALS Scale and ALS Functional Rating Scale-R (ALS FRS-R). RESULTS: Using the Pearson Product-Moment Correlation, an expected high linear association between the two disease specific neurological scales was demonstrated. Both dysphagia scales were found to be reliable. Interrelationship evaluation showed a low association between Norris and ALS FRS-R scores and DOSS and APRS. However, examination found specific subsections to be significantly correlated, particularly the Norris bulbar sections (NBS) and the DOSS. CONCLUSIONS: Generic dysphagia scales are reliable indicators of dysphagia in ALS. The bulbar components of the ALS specific scales is sensitive to dysphagia. The bulbar section of the Norris scale can be utilised as an independent and reliable indicator of the severity of dysphagia in ALS. In the absence of availability of detailed swallowing assessment using videofluoroscopy, these scales, i.e., the Norris and to a lesser degree the ALS FRS-R bulbar sections, are adequate to diagnose and follow clinically significant dysphagia in ALS, and can be used as an indicator for dysphagia treatment initiation.

Adult↗
PubMed2003

Proton transfer reaction ion trap mass spectrometer.

Proton transfer reaction mass spectrometry is a relatively new field that has attracted a great deal of interest in the last few years. This technique uses H(3)O(+) as a chemical ionization (CI) reagent to measure volatile organic compounds (VOCs) in the parts per billion by volume (ppbv) to parts per trillion by volume (pptv) range. Mass spectra acquired with a proton transfer reaction mass spectrometer (PTR-MS) are simple because proton transfer chemical ionization is "soft" and results in little or no fragmentation. Unfortunately, peak identification can still be difficult due to isobaric interferences. A possible solution to this problem is to couple the PTR drift tube to an ion trap mass spectrometer (ITMS). The use of an ITMS is appealing because of its ability to perform MS/MS and possibly distinguish between isomers and other isobars. Additionally, the ITMS duty cycle is much higher than that of a linear quadrupole so faster data acquisition rates are possible that will allow for detection of multiple compounds. Here we present the first results from a proton transfer reaction ion trap mass spectrometer (PTR-ITMS). The aim of this study was to investigate ion injection and storage efficiency of a simple prototype instrument in order to estimate possible detection limits of a second-generation instrument. Using this prototype a detection limit of 100 ppbv was demonstrated. Modifications are suggested that will enable further reduction in detection limits to the low-ppbv to high-pptv range. Furthermore, the applicability of MS/MS in differentiating between isobaric species was determined. MS/MS spectra of the isobaric compounds methyl vinyl ketone (MVK) and methacrolein (MACR) are presented and show fragments of different mass making differentiation possible, even when a mixture of both species is present in the same sample. However, MS/MS spectra of acetone and propanal produce fragments with the same molecular masses but with different intensity ratios. This allows quantitative distinction only if one species is predominant. Fragmentation mechanisms are proposed to explain the results.

Journal Article↗
PubMed2003

An outcome study of riluzole in amyotrophic lateral sclerosis--a population-based study in Ireland, 1996-2000.

Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period. Using data from the Irish ALS Register, we examined the survival of patients diagnosed with ALS between 1 January 1996 and 31 December 2000 who attended a general neurology clinic (n = 264 patients, MD = 16). An intention to treat analysis is employed. 149 (61 %) patients were prescribed riluzole and the remaining 99 (39 %) were not. Riluzole therapy reduced mortality rate by 23 % and 15 % at 6 and 12 months respectively and prolonged survival by approximately four months. This beneficial effect was lost in prolonged follow-up. Suspected or possible ALS patients receiving riluzole experienced similar improvement in survival as the overall cohort. Survival benefit was more marked among patients with bulbar-onset disease. Multivariate analysis did not show riluzole to be an independent predictor of survival. We conclude that riluzole therapy improves ALS survival in everyday clinical practice by a short period of time. This beneficial effect is transient and stopping the medication in advanced ALS should be reconsidered. Bulbar-onset patients appear to particularly benefit from riluzole for unclear reasons. Our initial observations support riluzole use in early ALS.

Adult↗
PubMed2003

Supplementation of fexofenadine therapy with nedocromil sodium 2% ophthalmic solution to treat ocular symptoms of seasonal allergic conjunctivitis.

PURPOSE: Ocular symptoms are often under-treated in patients with allergic rhinoconjunctivitis. The efficacy of fexofenadine hydrochloride 60 mg capsules supplemented with nedocromil sodium 2% ophthalmic solution was evaluated to determine the optimal drug regimen for control of ocular allergic symptoms. METHODS: In this 5-week, open-label, randomized, multicentre comparative study, 89 patients with documented ragweed pollen allergy received fexofenadine b.i.d. with nedocromil rescue, fexofenadine q.d. with nedocromil b.i.d., or fexofenadine rescue with nedocromil b.i.d. during the ragweed pollen season. RESULTS: For all regimens, mean symptom severity scores for itching, burning, tearing, redness, grittiness, discharge, light sensitivity and swelling improved significantly (P < 0.003). Similarly, all groups experienced significant (P < 0.02) improvement in all clinical signs: erythema, oedema, discharge, conjunctival injection and conjunctivitis, as well as quality-of-life scores (P < 0.0001). All regimens reduced overall symptom severity scores after 5 min (P < 0.05) with relief persisting over 12 h (P < 0.03). Improvements in mean symptoms, signs and quality-of-life scores were similar among the treatment groups as were onset and duration of action even though patients in two of the three study arms were taking one-half or less of the recommended fexofenadine dosage. Patients and physicians judged the regimens containing lower fexofenadine dosages (with nedocromil b.i.d.) to be more effective overall than the regimen containing the highest fexo-fenadine dosage (with nedocromil as rescue only). CONCLUSIONS: Supplementation of oral fexofenadine therapy with nedocromil sodium 2% ophthalmic solution relieves ocular symptoms of seasonal allergic rhinoconjunctivitis, allowing control of rhinal symptoms with half the recommended dosage of fexofenadine.

Adolescent↗
PubMed2003

Differential impairment of person-specific knowledge in a patient with semantic dementia.

We report the case of ST, a 61-year-old gentleman of superior intelligence, who presented with a five-year history of slowly progressive word finding difficulty for proper names. MRI (magnetic resonance imaging) showed marked atrophy in the left anterior temporal lobe and SPECT (single photon emission computed tomography) demonstrated hypoperfusion in the left anterior and inferior temporal region. A detailed behavioral analysis of the integrity of his semantic system revealed naming deficits for both proper and common names. ST also showed severe impairments in person-specific semantic knowledge, but preservation of knowledge for famous places and common objects. ST's semantic knowledge deficit for people emerged whether he was tested with the faces or the names of famous individuals. Variables that affect name retrieval, such as familiarity, age of acquisition, and frequency of concept encounter, do not account for the selective impairment of person-specific knowledge evidenced by ST. Qualitative differences between the nature of knowledge representations for people and for common objects may underlie this effect. Disruptions in left temporal regions associated with semantic processing may be sufficient to produce a selective deficit in person-specific knowledge.

Attention↗
PubMed2003

Respiratory management of pediatric patients with spinal cord injuries: retrospective review of the duPont experience.

Pulmonary complications contribute to morbidity and mortality in spinal cord injuries (SCIs). A retrospective review of 20 years of experience with tracheostomy- and ventilator-dependent SCI children is presented. The authors developed and analyzed a database of 47 children (average age = 11.4 years). Of the patients, 27% had concomitant brain injuries, 6% had prior histories of reactive airway disease, and 2% had thoracic fractures. Injuries were caused by motor vehicle accidents (53%); gunshot wounds (19%); sports-related accidents (19%); and vascular injuries, transverse myelitis, or spinal tumors (8%). Of the injuries, 52% were high level (C1 to C2) and 48% were mid- or low level (C3 to C5). Two groups were analyzed for demographic information. Complications included tracheitis, atelectasis, and pneumonia. Mean tidal volume was 14 cm2/kg (maximum = 22 cm2/kg). Bedside lung function parameters were attempted to assess readiness and the rapidity of weans. T-piece sprints were used to successfully wean 63% of patients. Successfully weaned patients were compared with those not weaned. No deaths or readmissions for late-onset respiratory failure postwean occurred. The authors' clinical impression favors higher tidal volumes and aggressive bronchial hygiene to minimize pulmonary complications and enhance weaning. Successfully weaned patients had fewer complications. A critical pathway for respiratory management of SCI children is presented.

Adolescent↗
PubMed2002

Once-daily administration of budesonide Turbuhaler was as effective as twice-daily treatment in patients with mild to moderate persistent asthma.

In a double-blind, randomized, placebo-controlled trial, 288 patients with mild to moderate persistent asthma currently on inhaled glucocorticosteroids (GCSs) were treated with budesonide Turbuhaler, 200 microg once every night (q.n.), 100 microg twice-daily (b.i.d.), or placebo b.i.d. After 12 weeks, morning peak expiratory flow (PEF) increased in both groups treated with budesonide but decreased in placebo-treated patients. Symptom scores and bronchodilator use were significantly reduced in both groups receiving active treatment (p = 0.023-0.0001) compared with patients treated with placebo. There was no significant difference in outcome measurements between the two budesonide regimens. Thus, patients with mild to moderate persistent asthma receiving b.i.d. treatment with inhaled GCSs can usually be switched to budesonide Turbuhaler, 200 microg, q.n. without loss of asthma control.

Administration, Inhalation↗
PubMed2002

Amyotrophic lateral sclerosis: enteral nutrition provision--endoscopic or radiologic gastrostomy?

PURPOSE: To retrospectively evaluate gastrostomy placement in patients with amyotrophic lateral sclerosis (ALS) to determine the insertion method of choice. MATERIALS AND METHODS: During 3(1/2) years, 36 patients with ALS (19 men, 17 women; mean age, 54 years; age range, 37-69 years) underwent gastrostomy. Twenty patients were primarily referred for percutaneous endoscopic gastrostomy (PEG) and 16 for percutaneous radiologic gastrostomy (PRG). Gastrostomy method, success rate of each technique, and reason for procedure failure were reviewed in each patient. Forced vital capacity (FVC) prior to gastrostomy was recorded. PEG was performed with a pull-through technique after transillumination of the abdominal wall. PRG was performed with fluoroscopic guidance and T-fastener gastropexy. A log-rank test was used to compare survival rates after PRG and PEG, and a Wilcoxon rank sum test was used to evaluate the influence of declining FVC on PEG success. The Kaplan-Meier product limit method was used to estimate survival probabilities. RESULTS: Of the 20 patients referred for PEG, 11 had successful results. The nine failures (45%) resulted from failure to transilluminate the abdominal wall. All 16 patients primarily referred for PRG underwent successful gastrostomy. The nine patients in whom PEG failed underwent subsequent successful PRG. In patients with diaphragmatic palsy and a high subcostal stomach, an angled subcostal approach (n = 6) or intercostal approach (n = 2) was required at PRG. One death occurred in the PEG group (9%) because of procedure-related aspiration, and a second patient from the PEG group required laparotomy for postprocedural peritonitis. One death occurred in the PRG group (4%) because of inadvertent placement of the feeding tube in the peritoneal cavity. There was no significant difference between PEG and PRG in patient survival. FVC did not have a statistically significant influence on PEG failure. CONCLUSION: Results show PRG to be the method of choice.

Adult↗
PubMed1996

Detection of Progression of Coronary Artery Disease in the Elderly.

In order to assess the progression of coronary artery disease (CAD) in the elderly, we evaluated 91 patients aged 75 years or older who had undergone 2 consecutive angiograms without intervening revascularization. Progression was defined as an absolute increase in lumen narrowing by at least 20% with minimum stenosis of 50% at second angiogram, or progression to total occlusion of any preexisting lesion. Progression involving at least 1 vessel was observed in 63% of patients. Only 6% of initially normal or insignificantly diseased segments showed progression. In contrast, 72% of segments that progressed to total occlusion had shown an initial narrowing greater than 75%. Progression occurred in 100% of patients with an interval myocardial infarction, but in no patients with symptomatic valvular disease. No regression was observed, while 7 of 36 (19%) of initially occluded segments had recanalized. We conclude that progression of CAD in the elderly occurs at rates similar to those observed in a younger population; however no correlation could be found between the rate of progression and either risk factors or elapsed time between angiographic studies.

Journal Article↗
PubMedDate not supplied

Twice-daily and once-daily nedocromil sodium 2% ophthalmic solution for the treatment of seasonal allergic conjunctivitis.

In this 8-week open-label, prospective study, 30 patients with grass pollen allergy and ocular itching instilled nedocromil sodium 2% ophthalmic solution twice daily for a 5-day baseline period, followed by once-daily dosing thereafter. Physicians assessed clinical signs after the twice-daily period and after weeks 1 and 3 of the once-daily period; patients rated ocular symptoms daily. Use of specified rescue medication was permitted. Symptom scores for ocular itching, stinging, redness, swelling, burning, tearing, and light sensitivity did not differ significantly between the dosage periods. Scores for erythema, edema, conjunctival injection, and the entire conjunctiva decreased slightly during once-daily administration; discharge scores were unchanged. Of the 20 patients who used rescue medication, only 5 increased their usage by more than two doses per week during the once-daily period. Eighty-three percent of patients were willing to continue the once-daily regimen during the next allergy season. Physicians rated overall control of seasonal allergic conjunctivitis with once-daily administration as "good" or "moderate" in 100% of the patients; 93% of patients applied those ratings themselves. Nedocromil sodium 2% ophthalmic solution instilled once daily maintains control of symptoms in patients who are established on a twice-daily regimen.

Adolescent↗
PubMedDate not supplied

Passive exoskeletons for assisting limb movement.

This article presents the state of the art in passive devices for enhancing limb movement in people with neuromuscular disabilities. Both upper- and lower-limb projects and devices are described. Special emphasis is placed on a passive functional upper-limb orthosis called the Wilmington Robotic Exoskeleton (WREX). The development and testing of the WREX with children with limited arm strength are described. The exoskeleton has two links and 4 degrees of freedom. It uses linear elastic elements that balance the effects of gravity in three dimensions. The experiences of five children with arthrogryposis who used the WREX are described.

Adolescent↗