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Maximizing function in Alzheimer's disease: what role for tacrine?

As the number of elderly persons continues to increase, family physicians will be caring for more patients with Alzheimer's disease. The treatment plan for patients with this incurable illness should be directed at optimizing their physical and psychosocial functioning and supporting their caregivers. Tacrine is the first medication proven to ameliorate the symptoms of Alzheimer's disease. This drug has been approved by the U.S. Food and Drug Administration for use in patients with mild to moderate Alzheimer's disease as evidenced by a score between 10 and 26 on the Mini-Mental State Examination. Tacrine can produce modest dose-related improvements in cognitive function and global measures of patient function. Such improvements only occur in 25 percent of patients treated with tacrine. On discontinuation of the drug, the patient's cognitive function returns to the level that would be expected if no treatment had been given. Both the degree of cognitive improvement and the severity of cholinergic symptoms increase with higher doses of tacrine. Thus, patients receiving tacrine therapy must be monitored for both clinical efficacy and adverse effects of the medication.

Alzheimer Disease↗

Longitudinal study of cerebral blood flow in Alzheimer's disease using single photon emission tomography.

Ten patients with probable Alzheimer's disease were assessed at baseline and a mean 2 years later using a battery of neuropsychological tests, CT scans and Tc99m-HMPAO SPECT scans. The subjects had declined significantly in their functional indices. Cerebral perfusion measures declined in the parietal lobes, left hemisphere and whole brain, but the overall decline did not reach statistical significance. The decline in brain perfusion did not correlate significantly with the decline in various indices of neuropsychological function, either globally or for specific brain regions. The index of cerebral perfusion correlated significantly with global indices of neuropsychological function at baseline but not at follow-up. No single perfusion index was a significant predictor of clinical progression of dementia.

Adult↗

[Interferon beta1-a IM once weekly does not modify general psychological function in the first months after therapy in patients with relapsing-remitting multiple sclerosis].

INTRODUCTION: Psychological troubles are common in multiple sclerosis but their underlying etiology is still controversial. METHODS: The objective of this open, non comparative, multicenter study was to assess changes in global psychological functioning in new multiple sclerosis patients during the first 3 months of treatment with intramuscular interferon beta-1a once weekly (Avonex). This functioning was rated every 4 weeks with the GAF (Global Assessment Functioning) scale. Depression measured on MADRS (Montgomery & Asberg Depression Rating Scale), clinical global impression (CGI) on patients'psychological status and clinical as well as biological tolerance were also assessed every 4 weeks. RESULTS: Five hundred and ninety-nine patients (71.4 percent women), aged 39.4 years were included. No clinically significant difference in mean GAF score between baseline and the end of the first 3 months of interferon beta-1a IM treatment (main evaluation outcome) was found. Similar results were obtained on MADRS scale. CONCLUSION: No clinically significant alteration of global psychological functioning, including symptoms of depression, was observed during the first 3 months of treatment with interferon beta-1a IM.

Adjuvants, Immunologic↗

Assessment of reversible myocardial dysfunction in chronic ischaemic heart disease: comparison of contrast-enhanced cardiovascular magnetic resonance and a combined positron emission tomography-single photon emission computed tomography imaging protocol.

AIMS: The aim of the study was to compare, in patients with chronic ischaemic cardiomyopathy, contrast-enhanced cardiovascular magnetic resonance (ce-CMR) imaging and a combined (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and (99m)Tc-sestamibi single-photon emission computed tomography (SPECT) protocols for the prediction of functional recovery after revascularization, as assessed by cine CMR. METHODS AND RESULTS: Twenty-nine patients with ischaemic cardiomyopathy (ejection fraction 32 +/- 10%) were investigated with ce-CMR and PET/SPECT. For the assessment of global and regional functions, cine CMR was performed at baseline and at 6 months follow-up. For ce-CMR, the segmental extent of hyperenhancement (SEH) was quantitated, and for PET/SPECT, different viability categories were defined according to a validated quantitative protocol. Functional improvement was related to the SEH by ce-CMR, as well as to the viability categories by PET/SPECT. Sensitivity and specificity for the prediction of functional recovery at follow-up was 97 and 68% for ce-CMR and 87 and 76% for PET/SPECT. The positive predictive value was identical for both techniques (73%). However, ce-CMR achieved a higher negative predictive value (93 vs. 77%, respectively), indicating that ce-CMR may be superior to PET/SPECT for the identification of segments unlikely to recover function after revascularization. Both methods had a similar yield in the prediction of global functional improvement. CONCLUSION: ce-CMR is comparable with a PET/SPECT imaging protocol for the prediction of regional and global functional improvement after revascularization. However, ce-CMR may be superior to nuclear imaging for the identification of segments that are unlikely to recover function at follow-up.

Chronic Disease↗

Intraoperative echocardiographic assessment of global and regional myocardial function.

Intraoperative echocardiography is gaining increasing importance to the anesthesiologist and the surgeon in the management of high-risk patients undergoing cardiac and major noncardiac surgery. It can provide for the noninvasive, immediate assessment of global left ventricular function, and its determinants; preload, afterload, and myocardial contractility. In addition, abnormalities of regional myocardial function, as a marker of myocardial ischemia, can be easily identified. With the advent of transesophageal echocardiography, this imaging technique can be more widely applied without interfering with the surgical procedure, not only increasing our ability to adequately monitor the patient, but also guiding our therapy and providing additional insights into the physiological and pathophysiological processes affecting the heart during surgery.

Cardiac Surgical Procedures↗

Randomised trial of elective stenting after successful percutaneous transluminal coronary angioplasty of occluded coronary arteries.

BACKGROUND: The value of angioplasty in occluded coronary arteries is limited by a restenosis/reocclusion rate of 50-70%. In patients with subtotal occlusion, stent implantation has been shown to reduce clinical and angiographic restenosis. Retrospective observational studies have suggested that stenting could reduce restenosis in total occlusions. The value of sustained coronary patency on global and regional left ventricular function in this clinical setting has not been defined clearly. OBJECTIVES: To assess the medium term effect of elective intracoronary stent deployment after successful percutaneous transluminal coronary angioplasty (PTCA) of an occluded coronary artery. METHODS: Sixty patients with a total coronary occlusion successfully treated by PTCA were randomised to receive an intracoronary stent or no stent. Patients underwent clinical and angiographic follow up at six months. RESULTS: Thirty patients received a stent (group A) and 30 were treated by angioplasty alone (group B), all with initial success. One patient in group B required repeat angioplasty with stenting at 24 hours and one patient died after 10 days. Angiographic follow up was available for 57 patients. This showed a significantly reduced reocclusion rate in group A compared with group B (7% v 29%, p < 0.01) and a tendency to a reduced restenosis rate (22% v 40%, p = 0.105) in patients with no reocclusion. Left ventricular function, both global and regional, improved in group A. Only the regional left ventricular function in the area supplied by the target coronary artery improved in group B. Recurrence of symptoms and clinical events such as repeat angioplasty, coronary artery bypass grafting, death or myocardial infarction tended to be reduced in group A (4 (13%) v 9 (30%)). CONCLUSIONS: Intracoronary stent insertion is effective in reducing the rate of reocclusion and shows a trend towards reduced restenosis after opening of a total coronary occlusion by balloon angioplasty. Sustained patency of the target coronary artery is associated with improvement in global and regional left ventricular function.

Adult↗

Reliability and validity of DSM-IV axis V.

OBJECTIVE: The authors investigated the reliability and convergent and discriminant validity of the DSM-IV Global Assessment of Functioning Scale and two experimental DSM-IV axis V global rating scales, the Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale. METHOD: Forty-four patients admitted to a university-based outpatient community clinic were rated by trained clinicians on the three DSM-IV axis V scales. Patients also completed self-report measures of DSM-IV symptoms as well as measures of relational, social, and occupational functioning. RESULTS: The Global Assessment of Functioning Scale, Global Assessment of Relational Functioning Scale, and Social and Occupational Functioning Assessment Scale all exhibited very high levels of interrater reliability. Factor analysis revealed that the Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale are each more related to the Global Assessment of Functioning Scale individually than they are to each other. The Global Assessment of Functioning Scale was significantly related to concurrent patient responses on the SCL-90-R global severity index. The Social and Occupational Functioning Assessment Scale was significantly related to concurrent patient responses on the SCL-90-R global severity index and to a greater degree with both the Social Adjustment Scale global score and the Inventory of Interpersonal Problems total score. Although the Global Assessment of Relational Functioning Scale was not significantly related to any of the three self-report measures, it was related to the presence of clinician-rated axis II pathology. CONCLUSIONS: The three axis V scales can be scored reliably. The Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale evaluate different constructs. These findings support the validity of the Global Assessment of Functioning Scale as a scale of global psychopathology; the Social and Occupational Functioning Assessment Scale as a measure of problems in social, occupational, and interpersonal functioning; and the Global Assessment of Relational Functioning Scale as an index of personality pathology. The authors discuss further refinement and use of the three axis V measures in treatment research.

Adult↗

The intra-arterial injection of microglia protects hippocampal CA1 neurons against global ischemia-induced functional deficits in rats.

In the present study, we have attempted to elucidate the effects of the intra-arterial injection of microglia on the global ischemia-induced functional and morphological deficits of hippocampal CA1 neurons. When PKH26-labeled immortalized microglial cells, GMIR1, were injected into the subclavian artery, these exogenous microglia were found to accumulate in the hippocampus at 24 h after ischemia. In hippocampal slices prepared from medium-injected rats subjected to ischemia 48 h earlier, synaptic dysfunctions including a significant reduction of synaptic responses and a marked reduction of long-term potentiation (LTP) of the CA3-CA1 Schaffer collateral synapses were observed. At this stage, however, neither significant neuronal degeneration nor gliosis was observed in the hippocampus. At 96 h after ischemia, there was a total loss of the synaptic activity and a marked neuronal death in the CA1 subfield. In contrast, the basal synaptic transmission and LTP of the CA3-CA1 synapses were well preserved after ischemia in the slices prepared from the microglia-injected animals. We also found the microglial-conditioned medium (MCM) to significantly increase the frequency of the spontaneous postsynaptic currents of CA1 neurons without affecting the amplitude, thus indicating that MCM increased the provability of the neurotransmitter release. The protective effect of the intra-arterial injected microglia against the ischemia-induced neuronal degeneration in the hippocampus was substantiated by immunohistochemical and immunoblot analyses. Furthermore, the arterial-injected microglia prevented the ischemia-induced decline of the brain-derived neurotrophic factor (BDNF) levels in CA1 neurons. These observations strongly suggest that the arterial-injection of microglia protected CA1 neurons against the ischemia-induced neuronal degeneration. The restoration of the ischemia-induced synaptic deficits and the resultant reduction of the BDNF levels in CA1 neurons, possibly by the release of diffusible factor(s), might thus contribute to the protective effect of the arterial-injection of microglia against ischemia-induced neuronal degeneration.

Animals↗

Daily serial evaluation of left ventricular function with equilibrium radionuclide ventriculography following thrombolysis during acute myocardial infarction.

The changes in ventricular function after reperfusion by coronary thrombolysis are important when deciding about further definitive treatment necessary to ensure long-term vessel patency. The purpose of this study was to evaluate the early changes in left ventricular function after reperfusion. Left ventricular function was serially evaluated for 10 days in a group of 18 patients receiving intracoronary thrombolytic therapy for an acute myocardial infarction. Comparison of the global ventricular function in the successfully and unsuccessfully reperfused groups of patients showed significantly better function in the successful group than the unsuccessful group after the first day, which was maintained for the entire study period. Global and regional ventricular function in the successfully reperfused patients showed significant early improvement during the initial 72 h with maintenance of this improvement for the study period of 10 days. In the patients in whom reperfusion was unsuccessful, regional ventricular function showed no change, while the global function declined from day 5 to day 8 of the study period. This study then confirms the significant improvement in ventricular function after successful reperfusion. The time course pattern of the change in ventricular function indicates that the most significant improvement occurs within the first 72 h after reperfusion. These changes are similar to those previously reported in experimental animals.

Angioplasty, Balloon↗

The value of a completely automatic ECG gated blood pool SPECT processing method for the estimation of global systolic left ventricular function.

OBJECTIVES: Electrocardiographically gated blood pool SPECT (GBPS) is an interesting method for measuring left ventricular (LV) ejection fraction (LVEF) and volume. Recently, the availability of completely automatic GBPS processing software has been reported. We aimed to evaluate its reliability in measuring global LV systolic function. In addition, using the same population, we compared its reliability to that of three previously reported methods for processing GBPS. METHODS: We studied the performances of the new GBPS system for the evaluation of LVEFs and volumes in 29 patients. The LVEF provided by the planar equilibrium radionuclide angiography (planarLAO) and LV volumes provided by radiological LV contrast angiography (X-rays) were used as 'gold standards'. RESULTS: The new GBPS system failed in one patient. It shows good reproducibility for the measurement of both LVEF and volume. LVEF provided by this system is moderately correlated to planarLAO (r = 0.62; P < 0.001). The new GBPS constantly overestimates LVEF (P < 0.05). Results for LV volumes are moderately correlated to those obtained by X-ray investigation (r = 0.7; P < 0.001) but are significantly lower (P < 0.0001). There is a linear correlation between the average and the paired absolute difference for LV volumes (r = 0.52, P = 0.0001). CONCLUSIONS: The new, completely automatic, GBPS processing software is an interesting, moderately reliable method for measuring LVEF and volume. The performance of the method is lower than that previously reported for the same population for the other three GBPS processing methods.

Algorithms↗

Treatment late effects in long-term survivors of pediatric sarcoma.

PURPOSE: To assess health and musculoskeletal function in survivors of pediatric sarcomas. PATIENTS AND METHODS: Thirty-two individuals treated for Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), or non-rhabdomyosarcoma soft tissue sarcomas (NR-STS) with multi-modality therapy were enrolled on this cross-sectional study. Median age at the time of therapy was 15.4 years (range 7.1-34.2), median age at the time of analysis was 37.4 years (17.5-55.4), and median duration of time elapsed from completion of therapy was 17.3 years (2.9-32.6). Participants underwent assessments of musculoskeletal functioning, cardiac function, metabolic and lipid analyses, renal and gonadal function, and psychological evaluation. RESULTS: This cohort of sarcoma survivors shows expected locoregional limitations in function of the area affected by sarcoma, and impaired global musculoskeletal functioning as evidenced by limited endurance and limited overall activity levels. The cohort also demonstrated substantial rates of cardiac dysfunction, elevated body fat index, hyperlipidemia, chronic psychological distress, and infertility in men (76%) and premature menopause (49%) in women. CONCLUSION: Sarcoma survivors demonstrate diminished locoregional and global musculoskeletal functioning which likely limit occupational opportunities and socioeconomic health. In addition, the combination of diminished cardiac reserve, limited activity levels, and lipid dysregulation in sarcoma survivors suggests that this population is at increased risk for cardiovascular disease, even many years following completion of sarcoma therapy. Sarcoma survivors may benefit from life long follow-up for cardiovascular disease and from occupational counseling upon completion of therapy.

Adolescent↗

Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study.

Cerebral white matter lesions (WMLs) have been associated with cognitive dysfunction. Whether periventricular or subcortical WMLs relate differently to cognitive function is still uncertain. In addition, it is unclear whether WMLs are related to specific cognitive domains such as memory or psychomotor speed. We examined the relationship between periventricular and subcortical WMLs and cognitive functioning in 1,077 elderly subjects randomly sampled from the general population. Quantification of WMLs was assessed by means of an extensive rating scale on 1.5-T magnetic resonance imaging scans. Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed, memory performance, and global cognitive function. When analyzed separately, both periventricular and subcortical WMLs were related to all neuropsychological measures. When periventricular WMLs were analyzed conditional on subcortical WMLs and vice versa, the relationship between periventricular WMLs and global cognitive function remained unaltered whereas the relationship with subcortical WMLs disappeared. Subjects with most severe periventricular WMLs performed nearly 1 SD below average on tasks involving psychomotor speed, and more than 0.5 SD below average for global cognitive function. Tasks that involve speed of cognitive processes appear to be more affected by WMLs than memory tasks.

Aged↗

Relative contributions of the anterior and posterior mitral chordae tendineae to canine global left ventricular systolic function.

The relative importance of the anterior and posterior mitral chordae tendineae to global left ventricular performance, independent of load, was determined by sequentially measuring the slope of the left ventricular peak isovolumetric pressure-volume relation in a canine model with the chordae of both, either, and neither mitral leaflet(s) intact. The order in which the chordae were severed was randomly assigned. Compared to baseline values (both chordae intact), severing the chordae of the anterior leaflet (posterior leaflet chordae intact) reduced the slope of the pressure-volume relation by 27% (p = 0.005) in 10 dogs; the slope decreased by an additional 16% (p = 0.017) when the posterior chordae were subsequently severed in this group. In 10 dogs randomized to the reverse order, the slope of the pressure-volume relation decreased by 17% (p = 0.021) after the posterior chordae were severed (anterior leaflet chordae intact); an additional 24% decrease in the slope (p = 0.001) occurred when the chordae of the anterior leaflet were subsequently severed in this group. The chordae of the anterior and posterior mitral leaflets have an additive, but statistically indistinguishable (p = 0.140), influence upon global left ventricular systolic performance; however, the contribution of the anterior chordae tends to be more important. Thus preservation of the anterior mitral leaflet and its chordal attachments to the papillary muscles during mitral valve replacement may have an equal or greater impact upon postoperative left ventricular function than mitral valve replacement with preservation of the posterior chordae; however, severing either the anterior or posterior chordae appears to be detrimental.

Animals↗

The effect of infrarenal aortic cross clamping and declamping on renal function in the pig.

Renal insufficiency following periods of infrarenal aortic cross clamping has been reported by some investigators but not by others, and conflicting views have been expressed concerning the ability of renal autoregulation to overcome the adverse circulatory effects of cross clamping. The object of this study was to examine the blood flow distribution to four layers within the renal cortex (subcapsular to juxtamedullary) and measure global renal function following application and release of an aortic cross clamp after 90 min. Nine juvenile female pigs weighing 25 to 50 kg were anaesthetized and subjected to intensive physiological monitoring. Throughout the study the blood pressure and cardiac output were maintained as close as possible to control levels by fluid administration and varying the depth of anaesthesia. Renal cortical blood flow was estimated by means of radionuclide labelled microspheres and global renal function was determined by the measurement of creatinine clearance. The aortic cross clamp was applied for 90 min immediately distal to the renal arteries and proximal to the inferior mesenteric artery. Cardiovascular and renal parameters were recorded on four occasions during each experiment, prior to, 10 and 60 min after cross clamping, and 30 min after clamp release. No significant changes in cardiac output, systemic blood pressure of global renal function were recorded during the study. There was, however, a significant fall in renal blood flow following release of the aortic cross clamp but this was not associated with any significant redistribution of blood flow within the renal cortex. In the pigs studied, the application of an infrarenal aortic cross clamp did not have any adverse effects on the cardiovascular system or on global renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Theoretical analysis of the relationship between regional and global measures of myocardial contractility.

Contractile function of the left ventricle is often measured regionally, particularly in intact animals. In this paper I dispute the validity of the common assumption that regional shortening accurately reflects whole-heart mechanics, even when contractility is homogeneous, by using an ellipsoidal model of the left ventricle to examine the relationship between measures of regional function and whole-heart function. Segment shortening and wall thickening are the most common measures of regional function, while the end-systolic pressure-volume relationship, or Emax, is a well-validated index of contractility in the whole heart. Assuming that the arterial end-systolic pressure vs stroke volume relationship is constant, segment shortening shows a monotonically increasing, convex relation to Emax. If, in addition, myocardium is considered an incompressible material, then wall thickening also shows a monotonically increasing, convex relation to Emax. Thus, segment shortening and wall thickening are quite insensitive when measuring high contractility and overly sensitive when measuring low-contractility. Finally, I consider the non-linear relationship between regional measures of function and global contractility, and thereby resolve apparently contradictory findings regarding the inotropic responsiveness of stunned myocardium.

Models, Cardiovascular↗

Development of body image, eating disturbance, and general psychological functioning in adolescent females: a replication using covariance structure modeling in an Australian sample.

OBJECTIVE: The current study is a follow up to a covariance structure modeling (CSM) investigation of predictors of body image, eating dysfunction, and general psychological functioning in U.S. adolescent females. METHOD: Four hundred and seventy Australian girls (13-17 years old) completed measures of teasing history, body dissatisfaction, global psychological functioning, dietary restraint, and bulimic behaviors. They were also measured in order to compute body mass index (BMI). CSM techniques were used to analyze the relationships between these latent variables. Two a priori models were tested, one was selected, and post-hoc model-fitting was undertaken. RESULTS: The final model indicated that BMI directly influenced teasing, which directly influenced body dissatisfaction. Body dissatisfaction influenced both global psychological functioning and restriction, whereas restriction had a direct influence on bulimia. Global psychological functioning also had a direct influence on bulimia. DISCUSSION: The results support previous research indicating that teasing and body dissatisfaction are risk factors for the development of eating disturbances.

Adolescent↗

Age-related changes in cognitive domains. A population-based study.

BACKGROUND AND AIMS: The aim of the present study is to describe the effects of aging on various cognitive domains (global cognitive function, executive function, motor speed) in a population sample of elderly men, and to describe how their age-related changes are influenced by education, depression, or prevalent cerebrovascular accidents (CEVD). METHODS: A cross-sectional observational study was conducted in a cohort of 334 men, 65 to 95 years old, living in rural communities, participating in the Italian cohort of two population studies--MATISS (Malattie cardiovascolari ATerosclerotiche Istituto Superiore di Sanità) and FINE (Finland, Italy, Netherlands, Elderly). Global cognitive function was measured by the Mini-Mental State Examination (MMSE), executive function by the Stroop test, motor speed by the Purdue Pegboard test, and depression by the CES-D test. Prevalence of cerebrovascular accidents (CEVD), myocardial infarction, and diabetes were evaluated by a questionnaire and a clinical examination. Blood pressure, and total and HDL cholesterol were measured. Current smoking status was self-reported. RESULTS: An age-associated decline in global cognitive functions, executive functions, and motor speed was observed. The decline is more apparent after the age of 85 for the MMSE, and after 75 for executive functions and motor speed. Logistic regression analysis revealed that age was independently associated with altered global cognitive functions, executive functions, and motor speed, even after adjusting for education, depression or prevalent CEVD. CONCLUSIONS: In a cohort of community-living elderly men aged 65 to 95 years, age-associated changes in mental functions are more evident after the age of 85. These changes are independent of education, depression, or prevalent CEVD.

Aged↗

Thromboxane A2 receptor-specific antagonism in hypothermic cardiopulmonary bypass.

Using a thromboxane A2 receptor-specific antagonist, SQ 30,741, this study was undertaken to define the role of thromboxane A2 in postischemic myocardial reperfusion injury and in the heparin-protamine reaction. Eighteen heparinized (300 units/kg) sheep were placed on cardiopulmonary bypass (CPB) after complete instrumentation, cooled to 28 degrees C, and had their aortas crossclamped for 1 hour. They were then rewarmed to 36 degrees C and weaned from CPB without inotropic support. Control sheep (n = 6) received a saline infusion throughout the procedure. Bolus animals (n = 6) received 5 mg/kg of SQ 30,741 at 5 minutes after discontinuation of CPB and before protamine sulfate administration. Infusion animals (n = 6) received an SQ 30,741 bolus of 5 mg/kg followed by a continuous infusion of 5 mg.kg-1 hr-1 of SQ 30,741 initiated before CPB. All animals received 5 mg/kg of protamine sulfate over a 15-second period 15 minutes after being weaned from CPB. Control animals exhibited significantly decreased global myocardial function after the 1-hour ischemic interval. Further significant functional decline and increase in pulmonary pressure occurred after protamine sulfate administration. Bolus animals experienced a similar postischemic injury, but had no further decrease in function following protamine infusion. Infusion animals had significantly improved global myocardial function after bypass compared with both other groups and were also protected from the deleterious effects of protamine sulfate administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗