The Effects of Previous Error and Success in Alzheimer's Disease and Mild Cognitive Impairment.

This work investigated in Alzheimer's disease dementia (AD), whether the probability of making an error on a task (or a correct response) was influenced by the outcome of the previous trials. We used the antisaccade task (AST) as a model task given the emerging consensus that it provides a promising sensitive and early biological test of cognitive impairment in AD. It can be employed equally well in healthy young and old adults, and in clinical populations. This study examined eye-movements in a sample of 202 participants (42 with dementia due to AD; 65 with mild cognitive impairment (MCI); 95 control participants). The findings revealed an overall increase in the frequency of AST errors in AD and MCI compared to the control group, as predicted. The errors on the current trial increased in proportion to the number of consecutive errors on the previous trials. Interestingly, the probability of errors was reduced on the trials that followed a previously corrected error, compared to the trials where the error remained uncorrected, revealing a level of adaptive control in participants with MCI or AD dementia. There was an earlier peak in the AST distribution of the saccadic reaction times for the inhibitory errors in comparison to the correct saccades. These findings revealed that the inhibitory errors of the past have a negative effect on the future performance of healthy adults as well as people with a neurodegenerative cognitive impairment.

Can you detect early dementia from an email? A proof of principle study of daily computer use to detect cognitive and functional decline.

OBJECTIVE: To determine whether multiple computer use behaviours can distinguish between cognitively healthy older adults and those in the early stages of cognitive decline, and to investigate whether these behaviours are associated with cognitive and functional ability. METHODS: Older adults with cognitive impairment (n = 20) and healthy controls (n = 24) completed assessments of cognitive and functional abilities and a series of semi-directed computer tasks. Computer use behaviours were captured passively using bespoke software. RESULTS: The profile of computer use behaviours was significantly different in cognitively impaired compared with cognitively healthy control participants including more frequent pauses, slower typing, and a higher proportion of mouse clicks. These behaviours were significantly associated with performance on cognitive and functional assessments, in particular, those related to memory. CONCLUSION: Unobtrusively capturing computer use behaviours offers the potential for early detection of neurodegeneration in non-clinical settings, which could enable timely interventions to ultimately improve long-term outcomes.

Dietary patterns and diet quality among diverse older adults: the University of Alabama at Birmingham Study of Aging.

OBJECTIVES: To characterize dietary patterns among a diverse sample of older adults (≥ 65 years). DESIGN: Cross-sectional. SETTING: Five counties in west central Alabama. PARTICIPANTS: Community-dwelling Medicare beneficiaries (N=416; 76.8 ± 5.2 years, 56% female, 39% African American) in the University of Alabama at Birmingham (UAB) Study of Aging. MEASUREMENTS: Dietary data collected via three, unannounced 24-hour dietary recalls was used to identify dietary patterns. Foods were aggregated into 13 groups. Finite mixture modeling (FMM) was used to classify individuals into three dietary patterns. Differences across dietary patterns for nutrient intakes, sociodemographic, and anthropometric measurements were examined using chi-square and general linear models. RESULTS: Three dietary patterns were derived. A "more healthful" dietary pattern, with relatively higher intakes of fruit, vegetables, whole grains, eggs, nuts, legumes and dairy, was associated with lower energy density, higher quality diets as determined by healthy eating index (HEI)-2005 scores and higher intakes of fiber, folate, vitamins C and B6, calcium, iron, magnesium, and zinc. The "western-like" pattern was defined by an intake of starchy vegetables, refined grains, meats, fried poultry and fish, oils and fats and was associated with lower HEI-2005 scores. The "low produce, high sweets" pattern was characterized by high saturated fat, and low dietary fiber and vitamin C intakes. The strongest predictors of better diet quality were female gender and non-Hispanic white race. CONCLUSION: The dietary patterns identified may provide a useful basis on which to base dietary interventions targeted at older adults. Examination of nutrient intakes regardless of the dietary pattern suggests that older adults are not meeting nutrient recommendations and should continue to be encouraged to choose high quality diets.

Antagonizing leukotriene B4 receptors delays cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection is a cellular immunological/inflammatory response that is, in part, directed by potent proinflammatory mediators. This study was designed to test the hypothesis that leukotriene B4 (LTB4) may have a role in graft rejection and that LTB4 receptor antagonists may be clinically useful in the treatment of allograft rejection. METHODS: We evaluated the potent and selective LTB4 receptor antagonist CP-105696 in a murine heterotopic cardiac allograft model with oral dosing daily for 28 days or in an induction protocol (day -1 to day 3). RESULTS: At a dose of 50 mg/kg/day (28 days), B10.BR (H2k) allografts transplanted into C57Bl/6 (H2b) recipients were significantly protected, as reflected by the mean survival time versus control grafts (27+/-20 days [n=10] vs. 12+/-6 days [n=14]; P=0.0146). Using an induction protocol (day -1 to day 3), CP-105696 at 100 mg/kg/day significantly prolonged allograft survival (33+/-23 days [n=9]; P=0.0026), but CP-105696 at 10 mg/kg/day did not (18+/-16 days [n=8]; P=0.1433). Syngeneic grafts survived indefinitely (n=11). Immunohistological evaluation of allografts at rejection revealed a mononuclear cell infiltrate composed primarily of CD3+ and CD11b+ (Mac-1+) cells, which were infrequent in syngeneic grafts. Allografts from mice treated with CP-105696 at 50 or 100 mg/kg/day demonstrated a selective reduction in beta2-integrin (Mac-1) expression on monocytes/macrophages, as demonstrated by CD11b staining density compared with allograft controls. CONCLUSIONS: The results suggest that LTB4 or other potential ligands for LTB4 receptors may be important mediators of allograft rejection and support the clinical evaluation of LTB4 receptor antagonists in human organ transplantation.

Attachment of gelatin films to tissue using argon beam coagulator.

Cross-linked gelatin films were bonded to heart muscle and to lung pleura and parenchyma using the electrical discharge of an argon beam radiofrequency coagulator. The bonds were stable in warm saline buffer for minutes to hours. Bonding was thought to partly occur through a mechanical interlock of film and tissue elements. The interdigitation of tissue and film arose during exposure to the argon beam, which denatured protein constituents of both, and created a fluidized state that rapidly coalesced.

Tissue response to biomaterials used for staple-line reinforcement in lung resection: a comparison between expanded polytetrafluoroethylene and bovine pericardium.

OBJECTIVE: A study in a canine model of lung-reduction surgery evaluated the tissue response to polytetrafluoroethylene (ePTFE) and bovine pericardium (BP) used for staple-line reinforcement. METHODS: In each of ten dogs, BP was placed in one lung and ePTFE in the other. The implants were retrieved at 30, 95, or 167 days after implantation and studied histologically. The connective tissue covering the implants was measured and analysis of variance was used to compare results with the two materials. RESULTS: At 30 days, the BP specimens showed focal chronic inflammation and thin tissue coverage, whereas the ePTFE specimens had no focal inflammation and thick tissue coverage. At 95 and 167 days, the inflammation in the BP specimens had resolved, but tissue coverage remained minimal, and there was no resorption of the BP. In the ePTFE specimens, tissue coverage had increased. Analysis of variance comparing representative tissue specimens showed that the tissue encapsulating the ePTFE was significantly thicker than that surrounding the BP (P < 0.0001). No air leaks, staple-line disruptions, or infections occurred in the study. CONCLUSIONS: Neither ePTFE nor BP is resorbable. Both materials have been used successfully, without resultant infections, for clinical staple-line reinforcement. The more favorable tissue response to ePTFE observed in this study may have clinical ramifications. Comparative clinical studies of the two materials are needed.

Quality of life and cardiorespiratory function in chronic heart failure: effects of 12 months' aerobic training.

OBJECTIVE: To examine the long-term benefits and safety of aerobic training in patients with chronic heart failure. DESIGN: Non-randomised control trial with 52 weeks follow up. SETTING: Outpatient cardiac rehabilitation referral centre. PATIENTS: Patients with compensated chronic heart failure (mean (SD) age 62 (6) years, New York Heart Association stage III, initial resting ejection fraction 22 (7)%). Experimental group of 17 men, 4 women; control group 8 men, 1 woman. INTERVENTIONS: Experimental group: progressive, supervised aerobic walking programme for 52 weeks. CONTROL GROUP: standard medical treatment. MAIN OUTCOME MEASURES: Six-minute walk distance, progressive cycle ergometer test to subjective exhaustion, disease-specific quality of life questionnaire, and standard gamble test, all measured at entry, 4, 8, 12, 16, 26, and 52 weeks. RESULTS: Control data showed no changes except a small trend to improved emotional function (P = 0.02 at 12 weeks only). Fifteen of the 21 patients completed all 52 weeks of aerobic training; two withdrew for non-cardiac reasons (16, 52 weeks). Three were withdrawn because of worsening cardiac failure unrelated to their exercise participation (4, 4, 8 weeks), and one had a non-fatal cardiac arrest while shopping (16 weeks). Gains of cardiorespiratory function plateaued at 16-26 weeks, with 10-15% improvement in six-minute walk, peak power output, and peak oxygen intake linked to gains in oxygen pulse and ventilatory threshold and reductions in resting heart rate. Marked improvements in quality of life followed a parallel course. CONCLUSIONS: Aerobic training is safe and beneficial in compensated chronic heart failure. Gains in aerobic function and quality of life persisted over a programme lasting 52 weeks.

The use of on-line image verification to estimate the variation in radiation therapy dose delivery.

PURPOSE: On-line radiotherapy imaging systems provide data that allow us to study the geometric nature of treatment variation. It is more clinically relevant to examine the resultant dosimetric variation. In this work, daily beam position as recorded by the on-line images is used to recalculate the treatment plan to show the effect geometric variation has on dose. METHODS AND MATERIALS: Daily 6 MV or 18 MV x-ray portal images were acquired using a fiberoptic on-line imaging system for 12 patients with cancers in the head and neck, thoracic, and pelvic regions. Each daily on-line portal image was aligned with the prescription simulation image using a template of anatomical structures defined on the latter. The outline of the actual block position was then superimposed on the prescription image. Daily block positions were cumulated to give a summary image represented by the block overlap isofrequency distribution. The summary data were used to analyze the amount of genometric variation relative to the prescription boundary on a histogram distribution plot. Treatment plans were recalculated by considering each aligned portal image as an individual beam. RESULTS: On-Line Image Verification (OLIV) data can differentiate between systematic and random errors in a course of daily radiation therapy. The data emphasize that the type and magnitude of patient set-up errors are unique for individual patients and different clinical situations. Head and neck sites had the least random variation (average 0-100% block overlap isofrequency distribution width = 7 mm) compared to thoracic (average 0-100% block overlap isofrequency distribution width = 12 mm) or pelvic sites (average 0-100% block overlap isofrequency distribution width = 14 mm). When treatment delivery is analyzed case by case, systematic as well as random errors are represented. When the data are pooled by anatomical site, individuality of variations is lost and variation appears random. Recalculated plans demonstrated dosimetric deviations from the original plans. The differences between the two dosimetric distributions were emphasized using a technique of plan subtraction. This allowed quick identification of relative "hot and cold spots" in the recalculated plans. The magnitude and clinical significance of dosimetric variation was unique for each patient. CONCLUSIONS: OLIV data are used to study geometric uncertainties because of the unique nature for individual patients. Dose recalculation is helpful to illustrate the dosimetric consequences of set-up errors.

Effects of explicit time-limits on the initial therapeutic alliance.

This study investigated the hypothesis that the setting of explicit time-limits in individual counseling enhances the formation of the therapeutic alliance. Students at a university-based counseling center were randomly assigned to a 5-session, time-limited therapy condition (n = 16) or a time-unlimited therapy condition (n = 15). Contrary to the hypothesis, statistical analyses showed no differences between audiotaped segments from the second and third therapy sessions rated on the Vanderbilt Therapeutic Alliance Scale.

On-line image verification in radiation therapy: an early USA experience.

The intense effort in the past 5 to 10 years to develop on-line image verification (OLIV) systems is made partly in anticipation of the increased verification demands of complex 3-dimensional (3D) conformal radiation therapy, and partly to improve on the current practice of weekly treatment verification. These systems allow convenient acquisition of daily portal images or many images during one treatment session. Systems based on fluoroscopic and scanning approaches can now be purchased from various vendors and are being evaluated at several radiation therapy centers. The performances of these systems vary, but all appear to be adequate for clinical use. At the Mallinckrodt Institute of Radiology, we have been conducting clinical on-line imaging for the past 3 years using a fiber-optic fluoroscopic system. Daily operation of the system requires coordinated participation of the physics and radiation therapy technology staff. The major consideration is in the management and evaluation of the large amount of verification images about each individual patient. At present, it is not clear whether the technology would be cost-effective in the clinical setting. However, it is clear that OLIV provides a powerful tool in enhancing our knowledge of treatment variation. The information will be invaluable in the development of improved treatment techniques. It is also likely that these systems will play a important part in the verification of 3D conformal radiation therapy.

Special issues in transfusion medicine.

This article reviews four controversial aspects of transfusion practices: the clinical circumstances, survival, and complications of massive transfusion; specific problems related to neonatal transfusion practices and the surgical support of the small child, including the appropriate age for red cells to be transfused, cytomegalovirus transmission, and the reduction in homologous donor exposures; the clinical presentation, incidence, and prevention of transfusion-associated graft-versus-host disease; and the biochemistry, function, genetics, and clinical indication for replacement therapy of antithrombin III.

Development and application of modern devices in vascular surgery including comment on modern antithrombotic and lytic drug therapy.

Since modern vascular surgery started with the discovery of heparin and the development of modern vascular grafts including autogenous saphenous vein, the speciality has been technologically driven. At the outset, vascular surgery depended almost entirely on the development of specialized clamps, instruments, and tools to permit decisive attack on the problems of occlusion. No less important was the development of insight into the basis of atherosclerosis, the discovery that atherogenesis with thrombosis is electrochemically identical to corrosion in pipes and therefore subject to chemical forces, which have not yet been delineated, as well as mechanical forces which have been delineated and permit one to attack the atheroma directly. Thus, classic replumbing techniques including bypass and endarterectomy have long been a part of the fundamental firmament of vascular surgery. Most recently, modern techniques in cleaning out blood vessels, removing occlusive processes, and modern thrombus-dissolving enzymes have all come to the forefront. Frequently multiple techniques are used simultaneously. This article is an attempt to summarize various aspects of this activity and describe several of the patents which have been seminal in the ultimate application of the techniques in both experimental animals and man. This should be the first of a series of efforts to summarize this area. The process of change has never been more kinetic than now.

Radio-frequency ablation: effect of voltage and pulse duration on canine myocardium.

The purpose of this investigation was to examine in vivo the relationship of radio-frequency (RF) pulse voltage and duration on the volume of tissue injury. RF 500-kHz pulses of 20-, 40-, and 60-V amplitude (RMS) were applied to the epicardium of 18 dogs for pulsing periods of 5-20 s. Systematic and quantitative tissue analysis was then performed after 30 days. No chronic lesions were evident on microscopic examination for 20-V RF pulse applications up to 15 s. Application of 20-V pulses for 20 s produced small lesions having a volume of 2.4 +/- 0.7 mm3. At 40 V, the volume of tissue injury ranged from 39.1 +/- 10.3 mm3 for 5 s of pulse application to 128.8 +/- 24.8 mm3 for 20 s of pulse application. Over the first 15 s of 40-V pulse application, the volume of tissue injury increased as pulse application time increased. There was no further increase in tissue injury for 40-V pulsing durations greater than 15 s. At 60 V, volumes of tissue injury ranged from 122.7 +/- 33.5 mm3 at 5 s to 313.6 +/- 73.7 mm3 at 20 s. Lesion size increased significantly for pulse durations of up to 10 s. Thereafter, 60-V pulses yielded little increase in tissue injury. In addition, persistent 60-V pulsing for periods greater than 9 s duration resulted in arcing and tissue vaporization in 28% of the applications. Thus RF energy is limited in its ability to create safe and effective tissue injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Biophysical and anatomical considerations for safe and efficacious catheter ablation of arrhythmias.

The development of catheter ablation techniques for therapy of cardiac arrhythmias continues to evolve. Although many patients have benefited from catheter ablation procedures, failure to ablate the arrhythmogenic substrate and complications from the pulse used in these procedures remain too frequent occurrences. The purpose of this review is to focus on these problems of inefficacy and safety with attention directed to the role various direct current and radiofrequency pulses have had in the genesis of these difficulties.

Massive transfusion in adults. Diagnoses, survival and blood bank support.

In a retrospective study covering a 2-year period (1986-1987), 125 patients received massive blood transfusion. Trauma accounted for only 29% of the cases. The larger nontrauma diagnostic categories were: gastrointestinal hemorrhage, 31%; cardiovascular surgery, 12%, and oncology cases, 9%. The overall survival rate was 60%; survival rates ranged from 38% for patients with hepatic failure to 100% for obstetric cases. Clinically important alloantibodies were present in 4%, and transfusion reactions occurred in 9%. Massive transfusions accounted for a significant proportion of total blood component usage: at least 12% of the yearly total red cell units, 20% of plasma, and 14% of platelets transfused.

Effect of voltage and charge of electrical ablation pulses on canine myocardium.

Multiple paired lesions produced by a train of high-voltage low-charge rectangular pulses (20 A, 30 microsecond) and a train of low-voltage high-charge rectangular pulses (2 A, 300 microsecond) were made to the left ventricular epicardium of 23 dogs to determine the relative influence of voltage and charge delivery on injury of canine myocardium. Both pulsing methods contained equal amounts of energy (15 J) delivered over equal periods of time (100 ms), and both pulsing methods were nonarcing and therefore nonbarotraumatic. The volume of cardiac tissue injury resulting from both types of pulses was then evaluated from planimetered serial histological sections after 1, 10, and 30 days. Over the 30-day period, lesion size progressively decreased to 56% of its original value for the high-voltage low-charge pulse. In contrast, lesion size from the low-voltage high-charge pulse remained relatively constant, decreasing only 12% of its original value. These results indicate that when energy delivery is held constant, voltage, not charge, is the dominant mediator of cell injury. Also, cells subjected to high voltages appear to recover partially over time with significantly less constancy of tissue injury than that seen with low-voltage high-charge pulses.

Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation.

We have tested the feasibility and effectiveness of a 2 year (average 16 +/- 7 months) walk/jog exercise program on 36 male orthotopic cardiac transplant patients (21 to 57 years old) seen initially 2 to 23 months after surgery. Comparison of initial exercise test results with those in 45 age-matched normal men showed the patients to have a lesser lean body mass (56 +/- 7 vs 63 +/- 8 kg, p less than .001), with a higher resting heart rate (104 +/- 12 vs 77 +/- 14 beats/min, p less than .001) and systolic (138 +/- 16 vs 129 +/- 17 mm Hg, p less than .001) and diastolic (95 +/- 14 vs 84 +/- 10 mm Hg, p less than .001) blood pressures. Peak power output was less than normal (101 +/- 27 vs 219 +/- 41 W, p less than .001), as was peak heart rate (136 +/- 15 vs 176 +/- 13 beats/min, p less than .001), peak oxygen intake (VO2max) (22 +/- 5 vs 34 +/- 6 ml.kg.min-1, p less than .001), and absolute anaerobic threshold (1.18 +/- 0.40 vs 2.04 +/- 0.40 liters.min-1, p less than .001). Peak ventilatory equivalent was higher (48 +/- 9 vs 37 +/- 61.1-1, p less than .001). Cardiac output (Q), as estimated by the CO2 rebreathing method, was slightly above normal at rest (p less than .01), but below normal at two submaximal work rates. The group's average weekly training distance was 24 km, with eight highly compliant patients progressing to 32 km or more weekly. After training, lean tissue increased (+2.4 +/- 3.1 kg, p less than .001), and resting values were reduced for heart rate (-4 +/- 11 beats/min, p less than .05), systolic (-13 +/- 20 mm Hg, p less than .001), and diastolic (-9 +/- 17 mm Hg, p less than .001) blood pressures. There were significant reductions in submaximal values for minute ventilation (VE), ratings of perceived exertion, and diastolic blood pressure at equivalent workloads. Peak values increased for power output (+49 +/- 34 W, p less than .001), VO2max (+4.0 +/- 6.0 ml.kg.min-1, p less than .001), VE (+20 +/- 20 l.min-1, p less than .001), and heart rate (+13 +/- 17 beats/min, p less than .001), and decreased for diastolic blood pressure (-8 +/- 15 mm Hg, p less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)