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At least 523 records · Page 29Linked to original sources

Comparing criteria of hearing impairment in the elderly: a functional approach.

We determined and compared the associations of four commonly used audiometric criteria of hearing impairment with two functional outcome measures in 152 aged persons screened in primary care medicine practices. The outcome measures were the Sickness Impact Profile (SIP, a measure of global function), and the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S, a communication-specific measure of functional impairment). There were five main findings. (1) The four criteria of hearing loss were not independent. (2) The criterion of loss chosen depends on the functional measure of impairment. (3) Functional hearing impairment may also be classified by the number of criteria met. (4) A large subset (21%) of aged persons met one criterion but had little in the way of communicative or global dysfunction. (5) Hearing handicap as measured by the HHIE-S was directly associated with global dysfunction as measured by the SIP.

Activities of Daily Living↗

Evidence for limited validity of the revised global assessment of functioning scale.

The study examined the concurrent validity of the revised Global Assessment of Functioning (GAF) scale, which is highly similar to the Social and Occupational Functioning Assessment Scale (SOFAS) in DSM-IV and which is designed to measure patients' functioning and not their clinical symptoms. Psychiatrists used the revised GAF to rate 337 psychiatric inpatients; the ratings were compared with nurses' ratings of the same sample using Lehman's Quality of Life Scale. Ratings on the revised GAF were most strongly correlated with ratings of clinical symptoms, not functioning. Reliance on the GAF as the only tool to assess patients' functioning may be problematic.

Activities of Daily Living↗

Extensive coagulation monitoring in patients after implantation of the MicroMed Debakey continuous flow axial pump.

Ventricular assist device (VAD) implantation is associated with impaired primary hemostasis and thromboembolic complications. Recently, a new generation of implantable continuous flow axial pumps was introduced into clinical application. To study the potential thrombogenic properties of this type of pump, we applied extensive platelet monitoring was applied. In our institution, 13 patients received the MicroMed DeBakey VAD as a bridge to transplantation. Routine coagulation tests (platelet count, activated partial thromboplastin time, prothrombin time, antithrombin III activity) and platelet function tests (whole blood aggregometry, thrombelastography, flow cytometry) were performed. No clinically relevant thromboembolic events were detected. No correlation was found between global function tests, platelet aggregation, and thrombelastography. No correlation was detected between platelet activation and hemolysis parameters. Platelet aggregation and coagulation index were significantly suppressed early after operation. A subsequent phase of hyper-aggregability, starting around day 6, suggested the initiation of antiaggregation therapy. Platelet activation markers were upregulated in the postoperative period but were returned to preoperative levels after initiation of aspirin. In contrast to routine coagulation monitoring, platelet function tests reflect in detail the coagulation status of blood pump recipients and the efficiency of antiaggregation therapy. Aspirin and dipyridamole therapy in addition to oral anticoagulation using phenprocoumon may contribute to platelet function and clot mechanics restoration and is, therefore, recommended for patients after VAD implantation.

Adolescent↗

A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease.

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimer's disease in earlier trials. The efficacy and safety of three dosages of Cere were investigated in this randomized, double-blind, placebo-controlled, study. Two hundred and seventy-nine patients were enrolled (69 Cere 10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and thereafter, two iv infusions per week for 8 weeks. Effects on cognition and clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning of the infusions using the CIBIC+ and the modified Alzheimer's Disease Assessment Scale (ADAS)-cog. At week 24, significant improvement of cognitive performance on the ADAS-cog (P=0.038) and global function (CIBIC+; P>0.001) was observed for the 10 ml dose. The 30 and 60 ml doses showed significant improvement of the global outcome but failed to show significant improvement of cognition. The results are consistent with a reversed U-shaped dose-response relationship for Cere. The percentage of patients reporting adverse events was similar across all study groups. Cere treatment was well tolerated and led to significant, dose-dependent improvement of cognition and global clinical impression.

Aged↗

Donepezil.

Donepezil is a specific and potent acetylcholinesterase inhibitor according to in vitro data. It displays primarily noncompetitive inhibitory activity. In vivo, donepezil inhibited acetylcholinesterase activity in human erythrocytes and increased extracellular acetylcholine levels in the cerebral cortex and hippocampus of the rat. Donepezil demonstrated efficacy in tests of reference memory in animals, but had less consistent activity in tests of working memory. Donepezil 5 or 10 mg/day was associated with significant improvements in cognitive function [assessed by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)] after 14 and 30 weeks and patient global function (Clinician's Interview-based Impression of Change incorporating caregiver input score) after 30 weeks, compared with placebo, in patients with mild to moderate Alzheimer's disease. After 2 years, donepezil 5 or 10 mg/day was associated with an ADAS-cog score approximately 4 points better than would be expected in untreated patients with mild to moderate Alzheimer's disease. The most common adverse events reported in association with donepezil 5 mg/day were gastrointestinal events (nausea/vomiting, diarrhoea, gastric upset and constipation) and dizziness. No hepatotoxicity was reported after 12 weeks' treatment.

Aged↗

[Relation of the cerebellum with cognitive function: neuroanatomical, clinical and neuroimaging evidence].

INTRODUCTION: Published studies in the last decades, employing a variety of methodologies, suggest that the cerebellum function is not only limited to motor control but also has an important role in cognition and emotion. DEVELOPMENT: In the present paper we review the main neuroanatomical and functional neuroimaging studies supporting the idea that the cerebellum has a role in non motor behavior. On the other hand, we expound the results of the neuropsychological studies of patients with cerebellar lesions. The deficits showed after cerebellar lesions include disturbances in executive functions, learning, memory, attention, visuo-spatial functions, language and personality change. Some studies propose that the cerebellum, through its afferent and efferent circuits with the cerebrum, perform a global function capable to influencing motor behavior, in cognitive functions and in emotion. A fault in this function would cause the behavioral deficits shown in patients with cerebellar lesions. CONCLUSION: The evidence available in the anatomical, functional and clinical studies support the conclusion that the cerebellum participates not only in motor functions, but also in cognitive functions and in emotion.

Brain↗

Functional exploration of the yeast (Saccharomyces cerevisiae) genome: use of a mini-Mu transposon to analyse randomly cloned DNA sequences.

The development of mega-sequencing techniques requires new methods for global functional analysis of cloned DNA fragments. We have developed a mini-Mu transposon adapted to yeast cloned DNA fragment analysis. This transposon allows us to do the following in a single construction: (i) to probe yeast cells for the presence of expressed open reading frames (ORFs) in the cloned DNA fragment; (ii) to localize these ORFs in the fragment and determine their transcription orientation; (iii) to use beta-galactosidase protein fusions to study regulation of these ORFs; and (iv) to disrupt the corresponding chromosomal genes. On a 5-kb yeast DNA sequence, we have verified the reliability of this new tool by comparing the data obtained with the mini-Mu transposon to those obtained by classical methods. This transposon should be of immediate use in the yeast genome sequencing programme.

Amino Acid Sequence↗

Autoperfusing ectothermic heart-lung preservation system.

A portable heart-lung preservation system was developed to enable distant organ procurement. In 8 dogs, a functioning heart-lung system was isolated, cannulated in situ, removed en bloc, and placed into a Plasmalyte-filled, temperature-controlled (15-38 degrees C) chamber. The perfusion circuit consisted of an adjustable-height, autologous-blood reservoir. The heart ejected through the aortic cannula with venous return (VR) into the superior vena cava. Respiration was maintained with a positive pressure ventilator. Intramyocardial tissue pressure (IMP), tissue pH, right atrial (RAP), aortic pressure (AOP), and cardiac output (CO) were monitored. Autoperfusion at normothermia and CO of 50 mL/min/kg resulted in early (3 h) deterioration of pulmonary function with progressive interstitial lung edema. Pulmonary dysfunction always preceded changes in regional myocardial contractile viability (peak IMP and d(IMP)/dt) and global function (CO, AOP). When tissue pH was regulated ectothermically (as in cold-blooded animals) (delta pH/degrees C = -0.015) the heart maintained a stable pumping mode (greater than 6 h) at myocardial temperatures of 17-28 degrees C, pH = 7.70-7.55, and heart rate of 25-50 bpm, respectively. The results indicate that a viable (greater than 6 h) autoperfused, working heart-lung system can be achieved by reducing the circulating blood flow to 30-50% of normal CO. More significantly, ectothermic alpha-stat modulation of perfusate pH and pCO2 allows a substantial reduction in organ temperature and metabolic demand without endangering induction of fibrillation and ultimate allograft failure.

Animals↗

Narcissistic personality disorder. A validity study and comparison to borderline personality disorder.

Seventeen former inpatients with NPD were retrospectively compared to 19 patients with schizophrenia, 26 with MAD and 33 patients with BPD in terms of longitudinal course and outcome, exploring the validity of the NPD diagnosis. Two illustrative cases were presented. Results suggest that NPD is a valid diagnostic entity, more distinct from schizophrenia than MAD. NPD probably differs from BPD in terms of equal sex distribution in NPD; poor social functioning, especially in the low level of satisfaction with heterosexual relationships in NPD at follow-up; more rehospitalization in NPD; probably poorer global functioning in NPD at admission; and probably poorer overall follow-up functioning in NPD.

Adult↗

Long-term randomized controlled trials of tailored-print and small-group arthritis self-management interventions.

OBJECTIVE: The objective of this study was to test the effectiveness of a mail-delivered, tailored self-management intervention (SMART) and to compare it with the classic Arthritis Self-Management Program (ASMP). METHODS: We performed 2 randomized controlled trials: 1) a study of 1090 participants randomized to SMART or USUAL CARE, and 2) a study of 341 participants randomized to SMART or ASMP. Dependent variables included disability, pain, depression, role function, global severity, doctor visits, and self-efficacy. SMART interventions were provided in months 0-18 and not reinforced. Results were assessed at 1, 2, and 3 years using analyses of covariance (ANCOVA). RESULTS: Compared with USUAL CARE, SMART participants at 1 year had decreased disability, improved role function, and increased self-efficacy (all P <0.01). At 2 years, decreases in global severity, doctor visits, and increases in self-efficacy (all P <0.01) were noted. At 3 years without reinforcement, no statistically significant effects remained. Compared with ASMP, SMART at 1 year had greater decreases in disability (P = 0.02) and increases in self-efficacy (P = 0.01). There were no differences at 2 years. At 3 years, role function (P = 0.04) and doctor visit (P = 0.03) were improved in ASMP as compared with SMART. Improvements from baseline were seen for nearly all variables in both groups. CONCLUSIONS: A mail-delivered arthritis self-management program, SMART, was similarly effective to the classic ASMP, with slightly better results in the first year and a slightly more rapid attenuation over the next 2 years. Results suggest that both programs are effective, and that the addition of a mail-delivered program could improve accessibility to arthritis self-management treatment.

Activities of Daily Living↗

Generalised biological function.

A physiological function can be described as a cycle based on a cusp bifurcation set in catastrophe theory. This cycle involves four phases that are successively developed along a functional potential, which is used to perform a given physiological act. The work we present is firstly based on a detailed study of the global function of vision, which covers a vast field extending from the molecular to cerebral scale. We then present other examples of generalised functions by expanding the frame of reference, from the scale of an organ to the scale of a whole organism with predation function, and to the scale of a social group with crisis management. We observed that the criteria remain the same, whether the function is considered on the scale of a cell membrane or a group of individuals organised into a cohort. Moreover, a so-called generalised function can be broken down into simpler sub-functions, each phase of the initial function containing the physiological act of each sub-function. It seems thus that a fractal extension may characterise the four-cusp spiral. This spiral is increasingly large as the types of sub-functions are multiplied. In functions relative to sociological science, such as crisis management, which are not natural but built and designed by humans, close attention must be paid to following the rules of these generalised biological functions.

Animals↗

Myocardial hibernation in coronary artery disease.

Coronary artery disease (CAD) is very prevalent in Western societies and is a leading cause of mortality and morbidity. Despite decreases in mortality rates from CAD over the past 30 years, ischemic heart failure remains an important problem because people with CAD are now living longer. Hibernating myocardium may be defined as reversible left ventricular dysfunction due to chronic CAD that shows improvement in function after revascularization. Many patients with ischemic cardiomyopathy have areas of hibernating myocardium, and thus can potentially show improvement in left ventricular regional and global function if they are revascularized. Whether hibernating myocardium represents an adaptive response to hypoperfusion in the face of chronic ischemia or whether it is a degenerative process is not entirely clear. Clearly, ultrastructural changes of de-differentiation are seen, and include loss of sarcomeres and the appearance of small mitochondria and glycogen accumulation. Although the mechanisms underlying the changes in morphology and depressed contractility, and the factors governing recovery of function are not clear, changes in adrenergic receptor density, cytokine upregulation, and the degree of fibrosis may all play a role. Identification of viability is commonly performed with dobutamine echocardiography or nuclear imaging. Because patients with extensive CAD and poor left ventricular systolic function are high-risk candidates for coronary bypass surgery, the preoperative identification of viability provides important prognostic information. Patients with viable myocardium who are treated with revascularization rather than medical therapy have better outcomes in terms of survival, left ventricular function, symptoms, and exercise capacity.

Chronic Disease↗

A 12-month, randomized, placebo-controlled trial of propentofylline (HWA 285) in patients with dementia according to DSM III-R. The European Propentofylline Study Group.

Alzheimer's disease (AD) and vascular dementia (VaD) share several features such as overactivation of microglial cells, damage induced by free radicals, glutamate and calcium overload. Propentofylline (HWA 285) has shown beneficial effects on all of these common elements, thus favouring its use in both subtypes of dementia. In a multinational, randomized, 12-month, double-blind, parallel-group study 260 out-patients with mild to moderate AD or VaD received 300 mg propentofylline (n = 129) or placebo (n = 131) three times daily 1 h before meals. The efficacy was tested at four independent rater levels (physician, psychologist, relative and patient) with assessments covering three major domains of dementia (global function, cognitive function and activities of daily living). After 12 months, the total patient population showed statistically significant treatment differences in favour of propentofylline for the global measures of dementia (Gottfries-Bråne-Steen scale, GBS, p = 0.001; Clinical Global Impressions, CGI, item I: p = 0.004, item II: p = 0.072) as well as for the cognitive measures (Syndrome Short Test, SKT, p = 0.002) and Mini-Mental State Examination (p = 0.001). The activities of daily living also showed a significant treatment difference in favour of propentofylline (p = 0.002). No significant treatment differences were found for rating scales performed by the patients. At month 12, VaD patients showed treatment differences in favour of propentofylline for the GBS total score (p = 0.006), CGI item I (p = 0.004), GGI item II (p = 0.044) and SKT (p = 0.028). Treatment differences for AD patients were all in favour of propentofylline and reached statistical significance for the SKT (p = 0.018). Propentofylline showed a good safety profile with respect to adverse events, vital signs, ECG and laboratory changes.

Activities of Daily Living↗

The pharmacology of donepezil: a new treatment of Alzheimer's disease.

Donepezil (donepezil hydrochloride, E-2020, Aricept, Eisai), launched in March 1997, was the first drug to be marketed for the symptomatic treatment of Alzheimer's disease (AD) in the UK. It had been launched a year earlier in the US where clinicians had already had experience of tacrine (THA). Donepezil is a piperidine based, potent, specific, non-competitive and reversible inhibitor of acetylcholinesterase (AChE). It is structurally dissimilar from other established cholinesterase inhibitors, namely THA (an acridine compound) and the carbamates, physostigmine and rivastigmine and has a pharmacokinetic and tolerability profile distinct from these agents. Experimentally, donepezil inhibits AChE activity in human erythrocytes and increases extracellular acetylcholine levels in the cerebral cortex and the hippocampus of the rat. Pharmacologically, donepezil has a half-life of approximately 70 h lending itself to once daily administration. The most common adverse events reported in clinical trials have been gastrointestinal, typically nausea, vomiting, diarrhoea and constipation. Headache, dizziness and sleep disturbance have also been reported; there has been no evidence of hepatotoxicity. Clinically a number of placebo-controlled trials have shown that donepezil 5 or 10 mg daily was associated with significant improvements in cognitive function, as assessed by the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS cog) after 12 or 24 weeks treatment. Significant improvements in global function and activities of daily living have also been demonstrated after 24 weeks treatment compared with placebo in patients with mild to moderate AD. Donepezil was the first rational treatment available in the UK for this disabling condition and as such received considerable attention. Much of the original attention was negative, ostensibly based on the scientific view that there was not enough published evidence to justify widespread use, but this was driven by concerns about the potentially high drug costs if all patients with AD were eligible to receive it. Considerable data have now been produced from Phase II, III and post-marketing surveillance. This drug evaluation will review the basic pharmacology of donepezil and place it in context with the trial data and the author's clinical experience with the drug.

Alzheimer Disease↗

Gender and strain variations in left ventricular cardiac function and mass determined with magnetic resonance imaging at 7 tesla in adult mice.

OBJECTIVES: We sought to assess with magnetic resonance imaging (MRI) the influence of strain type and gender on left ventricular (LV) global function and mass in 3 inbred mouse strains with a normal cardiac phenotype. MATERIALS AND METHODS: A total of 30 mice from 3 inbred strains (C57BL/6, 29S2/SvPasCrl, and C3HFeJ) were studied on a 7.05-T MR scanner using ECG-triggered cine sequences. LV mass and volumes were calculated with inclusion and exclusion of papillary muscles (PMs) in the LV wall. RESULTS: Significant differences were found with strain and gender (P < 0.001), with strain-effect but no gender-effect for ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV). There were no differences in LV mass between strains but lower values in female mice except in the C3H strain. The exclusion of PMs led to the relative underestimation of EF (-6.1%) and of LV mass (-6.4 mg) and the relative overestimation of EDV (6.3 microL) and ESV (5.3 microL). Inter- and intraobserver reproducibility was better when PMs were included. CONCLUSION: The use of MRI demonstrates cardiac interstrain and gender-related phenotypic diversities that are essential factors to consider when building genomic databases and designing studies.

Analysis of Variance↗

Effects of altered PaO2 and PaCO2 on left ventricular function and coronary hemodynamics in sheep.

The effects of acute changes in arterial carbon dioxide and oxygen tension, produced by altering the inspired gas mixtures while maintaining constant-volume intermittent positive pressure ventilation, on global function, regional left ventricular function, and coronary hemodynamics were studied in eight sheep during halothane anesthesia. Hypercapnia (Paco2, 73.5 +/- 2.3 mm Hg, mean +/- SD) increased heart rate, stroke volume, and cardiac output but decreased systolic shortening in the base of the left ventricle. Hypocapnia (PaO2, 24 +/- 1.5 mm Hg) decreased cardiac output and coronary flow below levels seen with hypercapnia but not below levels seen with normocapnia. Systolic shortening decreased in both apical and basal regions, and left ventricular relaxation was impaired as evidenced by a reduction of the nadir of LV dP/dt. Hypoxemia (PaO2, 39 +/- 1.5 mm Hg) elicited a hyperdynamic response of the circulation, increased coronary blood flow, and exhausted the coronary flow reserve. Neither changes in PaCO2 nor changes in PaO2 caused postsystolic shortening, although hypercapnia caused nonuniformity of contraction in the left ventricle. Thus, marked alterations in oxygen and carbon dioxide tensions do not cause left ventricular dysfunction, even though moderate hypoxia reduces the coronary flow reserve.

Anesthesia, Inhalation↗

Mitral annular descent velocity by tissue Doppler echocardiography as an index of global left ventricular function.

Mitral annular descent has been described as an index of left ventricular (LV) systolic function, which is independent of endocardial definition. Echocardiographic tissue Doppler imaging is a new technique that calculates and displays color-coded cardiac tissue velocities on-line. To evaluate mitral annular descent velocity as a rapid index of global LV function, we performed tissue Doppler imaging studies in 55 patients, aged 56 +/-15 years, within 3 hours of radionuclide ventriculographic ejection fraction. Tissue Doppler M-mode studies were obtained from each of 6 mitral annular sites, as follows: inferoseptal and lateral from apical 4-chamber views, anterior and inferior from apical 2-chamber views, and anteroseptal and posterior from apical long-axis views. Only 1 patient with severe mitral annular calcification was excluded. The group mean 6-site average peak mitral annular descent velocity was 5.5 +/- 1.9 cm/s (range 2.4 to 10.5), and the group mean ejection fraction was 49 +/- 18% (range 17 to 80%). The 6-site average peak annular descent velocity correlated linearly with LV ejection fraction (r = 0.86, SEE = 1.02 cm/s): LV ejection fraction = 8.2 (average peak mitral annular descent velocity) + 3%. The 6-site peak mitral annular descent velocity average >5.4 cm/s was 88% sensitive and 97% specific for ejection fraction >50%. The peak mitral annular descent velocity from the apical 4-chamber view (average from inferoseptal and lateral sites) correlated most closely with the LV ejection fraction (r = 0.85) as an individual view. Peak mitral annular descent velocity by tissue Doppler imaging has the potential to estimate rapidly the global LV function.

Adolescent↗