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Biomedical subjects

J Saxton

Publications and source records attributed to J Saxton.

At least 37 records · Page 2Linked to original sources

Neuropsychological assessment of the severely impaired elderly patient: validation of the Italian short version of the Severe Impairment Battery (SIB). Gruppo di Studio sull'Invecchiamento Cerebrale della Società Italiana di Gerontologia e Geriatria.

One hundred and sixty-nine severely demented patients were tested in a multicenter study with the short version of the Severe Impairment Battery which was translated into Italian with the purpose of adapting and validating it for an Italian population. Patients were enrolled in Italian geriatric centers participating in the Study Group on Aging Brain of the Italian Society of Gerontology and Geriatrics. Following thorough clinical and instrumental examinations, they were evaluated with the Mini Mental State Examination, the Clinical Dementia Rating, the Severe Impairment Battery (SIB), the Gottfries-Bråne-Steen Rating Scale for Dementia, the Activity of Daily Living index, and the Bedford Alzheimer Nursing Severity scale (BANS.s). The inter-rater reliability of the SIB was highly significant for the total score and its subtests; test-retest reliability showed the same significance in all items. Also concurrent validity, performed comparing the total SIB score with the total BANS.s score, was significant. The short Italian version of the SIB proved to be a very reliable tool for the evaluation of severely demented patients; it has the advantage of being easy to administer, it evaluates more cognitive domains that, are typically assessed in dementia, and has a wide enough range of scores to detect even small differences in the examined abilities.

Aged↗

Changes in indices of antioxidant status, lipid peroxidation and inflammation in human skeletal muscle after eccentric muscle actions.

This study investigated the effects of chronic muscle inflammation on indices of antioxidant status and muscle injury after eccentric exercise. Eight subjects each performed 70 maximal voluntary eccentric muscle actions on an isokinetic dynamometer, using the knee extensors of a single leg. Venous blood samples were collected into serum and EDTA tubes 5 and 3 days before exercise, immediately before exercise, and then again on days 3, 4, 5, 6, 7, 10 and 12 after the bout. Needle biopsies were taken from the vastus lateralis of six subjects, a week before exercise (baseline), and again on days 4 and 7 post-exercise. The concentrations of malondialdehyde in plasma and muscle were used as markers of lipid peroxidation. Creatine kinase activity, beta-glucuronidase activity and total antioxidant capacity were determined in serum. In muscle, aqueous and bound total antioxidant capacity, the aqueous sulphydryl concentration, and beta-glucuronidase and glucose-6-phosphate dehydrogenase activity were determined. No changes were detected in serum total antioxidant capacity, serum creatine kinase and beta-glucuronidase after the baseline biopsy. After exercise serum creatine kinase and beta-glucuronidase were elevated although other serum measures were unchanged. In muscle, aqueous and bound total antioxidant capacity, sulphydryls, glucose-6-phosphate dehydrogenase and beta-glucuronidase were all elevated. Despite evidence of inflammation in this study, muscle antioxidant status was not compromised, and malondialdehyde was unaltered in muscle and plasma. Therefore, this study provides no evidence that chronic muscle inflammation compromises antioxidant status or increases lipid peroxidation.

Adult↗

Maintenance of mobility in residents of an Alzheimer special care facility.

The cognitive and functional decline of demented residents in a specialized Alzheimer's facility was compared to that of demented residents living in a traditional nursing home. All residents met DSM-III-R criteria for dementia. The evaluation consisted of a clinical interview with patients and collateral assessments of cognition, general health, problem behaviors, depression, and a broad range of activities of daily living (ADLs) including mobility. Residents were evaluated at baseline and 6-month intervals over 18 months. Similar rates of decline were found in cognition and overall ADLs in both groups. However, the most striking finding was preserved mobility in residents of the Alzheimer's facility. This finding suggests that specialized facilities do not halt or slow the overall progression of cognitive and functional decline seen in Alzheimer's disease; however, residents of such facilities may show slower decline in mobility.

Accidental Falls↗

Changes in the secretion and glycosylation of fibronectin by human skin fibroblasts associated with tuberous sclerosis.

Fibroblasts from skin and skin lesions of patients with tuberous sclerosis (TS) and from skin of normal individuals were grown in culture. ELISA showed that the spent medium of those derived from TS skin lesions contained significantly more fibronectin (FN) than spent medium from the other cells. Amino acid compositional analysis of the FN from TS and normal sources revealed no substantial differences. However the FN of fibroblasts from TS-skin lesions was shown by HPAEC to contain a two- to three-fold increased content of carbohydrate. The changed monosaccharide composition was consistent with an increased content of N- and O-linked glycans and with the former containing polylactosamine chains. Fibroblasts from a normal individual were shown to proliferate more slowly and to produce larger cells when grown on FN from a TS skin lesion compared to growth on FN from normal skin.

Adolescent↗

The severe impairment battery: concurrent validity and the assessment of longitudinal change in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Measurement of cognitive dysfunction in the early stages of Alzheimer's disease (AD) has been well studied and there are many objective tests in use for this purpose. However, with the exception of clinical rating scales, such as the Clinical Dementia Rating Scale, Global Deterioration Scale, and Functional Assessment Staging, there are few objective measures of cognition in the more advanced stages of AD. Given a renewed interest in potential AD therapies, objective measures of mental functioning are needed to adequately assess change in more advanced AD patients. As part of an effort by the NIA-Alzheimer's Disease Cooperative Study to evaluate new measures of efficacy for their utility in treatment studies, the Severe Impairment Battery (SIB) was examined in a 1-year evaluation of change across a wide range of AD severity. The data suggest that the SIB is a reliable and valid measure of progression, particularly in persons with moderate to severe AD. The SIB may therefore be a useful outcome measure in clinical trials that include patients with more advanced stages of AD.

Aged↗

Purification and partial characterization of the high and low molecular weight form (S- and F-form) of invertase secreted by Aspergillus nidulans.

Two forms of secreted invertase have been purified from Aspergillus nidulans by ion-exchange and gel-filtration chromatography. S-invertase gave a single, broad, glycoprotein band on PAGE and SDS-PAGE corresponding in size to 185 and 78 kDa, respectively, compared with 94 and 110 kDa for F-invertase. The carbohydrate of S-invertase contained mainly mannose (14%) and less galactose (5%) whereas the F-form yielded mainly galactose (29%) and less mannose (12%). Three sharp bands of enzymically active glycoprotein for both the S-form (pI 4.9-5.2) and the F-form (pI 3-4.2) were observed after isoelectric focusing. Deglycosylation with Endo H simplified this pattern to one enzymically active protein band (pI 5.2). The aglycoenzymes gave narrow bands on PAGE and SDS-PAGE corresponding to 115 kDa and 60 kDa respectively for both S- and F-forms. The specific activity of S-invertase was three-fold higher than that of F-invertase both before and after deglycosylation. The Km values of the two forms of invertase were very similar. Significant homology existed between the N-terminal amino-acid sequences of S-invertase (and of internal peptides derived from it) and sequences of invertase from other species. It is suggested that the higher carbohydrate content in F-invertase results in the native enzyme existing as a monomer and having a greater negative charge and lower specific enzyme activity compared with the dimeric S-enzyme.

Amino Acid Sequence↗

[Validation of the Spanish version of the Severe Impairment Battery].

We examine the cognitive ability of 58 demented patients who were evaluated with the Spanish version of the Severe Impairment Battery (SIB). The SIB is composed of multiple simple subtests for memory, language, orientation, attention, visual perception and ability to construct. The battery also assesses social skills, praxis and the ability to respond appropriately to name. The mean SIB scores (72.55 +/- 17.99; range 8-99) correlated with mean scores (10.76 +/- 6.41; range 0-31) on the Spanish version of Folstein's Mini-Mental State Examination (MMSE). The SIB detected deterioration in the nine cognitive areas examined, even in the most severely impaired patients (MMSE = 0-6). These results indicate that the Spanish version of the SIB is a useful instrument for examining severely demented patients.

Aged↗

Severe impairment battery. A neuropsychological test for severely demented patients.

OBJECTIVE: Patients with progressive dementia invariably evolve to a stage where they can no longer be tested by standard neuropsychological tests. We studied the use of the Severe Impairment Battery (SIB) in such patients. DESIGN: Case series. SETTING: Geriatric long-term facility. PATIENTS: Sixty-nine patients who met the criteria of the Diagnostic and Statistical Manual for Mental Disorders, Revised Third Edition, for dementia were selected. The diagnosis of probable Alzheimer's disease was established according to the guidelines suggested by the National Institute of Neurologic and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association. There were 18 men and 51 women. The mean age of the population was 82.99 +/- 5.66 years. The mean Mini-Mental State Examination (MMSE) score was 10.71 +/- 6.14. MAIN OUTCOME MEASURE: To characterize the cognitive profile and evolution of severely demented patients by means of the SIB. RESULTS: The mean score on the SIB was 92.52 +/- 31.92, with a possible maximum of 133 points. Subgroups of patients with the most severe degree of dementia (MMSE scores of 0 to 5 and 6 to 11) showed significant differences in their scores on the SIB. In contrast, no differences were found between subgroups with MMSE scores of 6 to 11, 12 to 17, and greater than 17. Fifteen patients who had MMSE scores of less than 6 had SIB scores ranging from 7 to 81. All cognitive domains showed a deterioration across the four severity groups as determined by the MMSE scores and also during a longitudinal study performed on 26 patients. CONCLUSION: Our study indicates that the SIB is useful for the neuropsychological evaluation of severely demented patients and for their follow-up.

Aged↗

The natural history of Alzheimer's disease. Description of study cohort and accuracy of diagnosis.

OBJECTIVE: We describe the sampling, initial evaluation, and final diagnostic classification of subjects enrolled in a natural history study of Alzheimer's disease (AD). DESIGN: Volunteer cohort study. SETTING: Multidisciplinary behavioral neurology research clinic. PATIENTS OR OTHER PARTICIPANTS: Three-hundred nineteen individuals were enrolled in the Alzheimer Research Program between March 1983 and March 1988. Of these, 204 were originally classified with AD, 102 were normal elderly control subjects, and 13 were considered special cases. MAIN OUTCOME MEASURES: Final consensus clinical diagnosis, final neuropathologic diagnosis, and death. RESULTS: Of the 204 patients enrolled in the study, re-review after as many as 5 years of follow-up resulted in a final clinical classification of 188 with probable AD. Seven patients were believed to have a significant vascular component to the dementia, three were found to have developed depression, and six were excluded on other clinical grounds. Neuropathologic examination of 50 brains indicated definite AD in 43. After removing these seven misdiagnosed patients, the final group of probable/definite AD totaled 181 individuals. Accuracy of the baseline clinical diagnosis relative to neuropathology was 86%, and when follow-up clinical data were considered, 91.4%. Detailed neuropsychological testing yielded high sensitivity (0.988) and specificity (0.983) to dementia. Analyses of survival time from study entry until death revealed that older patients were significantly more likely to die during follow-up, but neither sex, years of education, nor pattern of cognitive impairment were related to survival. CONCLUSIONS: These data provide the descriptive basis for future studies of this cohort. They indicate that longitudinal follow-up of demented cases increases accuracy of diagnosis, and that detailed cognitive testing aids in early classification.

Aged↗

Long-term maintenance of weight loss following supplemented fasting.

One hundred two obese subjects were evaluated 2-3 years following treatment in a combined behavior therapy and very low calorie diet (VLCD) program. Average weight loss after VLCD was 27.2 kg; average weight loss at follow-up was 11.3 kg. Subjects who reported high levels of exercise were more successful in maintaining weight loss (17.5 kg at follow-up) than were those who exercised only moderately (9.3 kg), or not at all (5.6 kg). Enrolling in a weight loss maintenance program also minimized weight regain. Subjects who participated in maintenance for more than 8 months sustained more average weight loss at follow-up (19.1 kg) than did subjects who participated for 8 months or less (10.6 kg), or subjects who did not participate in maintenance (6.6 kg).

Adult↗

Comparison of the N-glycoloylneuraminic and N-acetylneuraminic acid content of platelets and their precursors using high performance anion exchange chromatography.

N-Acetylneuraminic acid (Neu5Ac) and N-glycoloylneuraminic acid (Neu5Gc) are distributed widely in nature. Using a Carbopac PA-1 anion exchange column, we have determined the ratios of Neu5Ac and Neu5Gc in hydrolysates of platelets and their precursors: a rat promegakaryoblastic (RPM) cell line and a human megakaryoblastic leukemia cell line (MEG-01). The ratio of Neu5Gc:Neu5Ac in cultured RPM cells is 16:1, whereas in platelet rich plasma and cultured MEG-01 cells it is 1:38 and 1:28, respectively. The nature of these sialic acids from RPM cells was verified using thin layer chromatography and liquid secondary ion mass spectrometry. The relevance of increased Neu5Gc levels in early stages of development is discussed.

Animals↗

Gallstone formation during weight-reduction dieting.

We investigated the development of gallstones over an 8-week period from the onset of dieting in 51 obese men and women and 26 nondieting control subjects. Gallbladder examinations were performed by abdominal real-time ultrasonography for the detection of gallstones. Initial sonography was performed prior to dieting and only those subjects in whom initial sonograms showed no gallstones or sludge were included in the study. Repeated sonography was performed at 4-week intervals for 8 weeks while they remained on a 2100-kJ/d diet. Initial weight of subjects prior to dieting averaged 105.9 +/- 3.8 kg (162% of ideal body weight) and decreased to 89.4 +/- 3.2 kg (137.3% of ideal body weight) after 8 weeks of dieting. Sonography performed after 4 weeks of dieting revealed new-onset gallbladder sludge in 1 subject and gallstones in 4 subjects. After 8 weeks of dieting sludge was detected in 3 subjects and gallstones in 13 (25.5%). In contrast, none of the nondieting subjects developed any detectable gallbladder abnormalities. During the dieting period, 1 of 51 subjects developed symptoms of biliary colic, necessitating cholecystectomy. On cessation of dieting with reinstitution of normal feeding, 2 additional subjects with stones developed symptoms severe enough to require cholecystectomy. In all 3 cases, cholesterol gallstones were recovered at the time of surgery. Eleven of the 13 patients with gallstones were followed up for 6 months after discontinuation of the diet. Besides the 3 undergoing cholecystectomy, 4 subjects had gallstones on follow-up ultrasound examination, while sonographically detectable gallstones had disappeared in 4 subjects. We conclude that this form of weight-reduction dieting predisposes to the development of gallstones and that gallstone formation is a risk of this type of prolonged calorie restriction. Dissolution or evacuation of gallstones may occur with resumption of a normal diet.

Adult↗

Neuropsychological assessment of the severely impaired elderly patient.

Although a number of standard scales exist for the assessment of the mildly to moderately demented patient, measurement of cognitive decline needs to be extended beyond this stage and into the range of functioning characteristic of the severely impaired individual. To do this, assessment techniques need to be developed which take into account the specific behavioral and cognitive deficits seen in severe dementia. Until such techniques are developed. a full and adequate account of the natural history of cognitive decline in AD is not possible. We have introduced a new assessment device, the Severe Impairment Battery, which evaluates a range of cognitive functioning in patients who are unable to complete standard neuropsychological tests. Preliminary results with this test are encouraging and suggest that, contrary to popular belief, many severely cognitively impaired patients are testable if appropriate techniques and strategies are applied.

Aged↗

Effects of chronic administration of benfluorex to rats on the metabolism of corticosterone, glucose, triacylglycerols, glycerol and fatty acid.

(1) Rats were fed on diets enriched with sucrose, beef tallow or corn oil and treated for 11-16 days with 50 mg of benfluorex per kg of body weight. By these times the growth rate and food intake were not significantly different from those of control rats. (2) Benfluorex approximately halved the concentration of circulating triacylglycerol in rats fed the beef tallow or sucrose diets. (3) It did not significantly alter the total lipoprotein lipase activity in diaphragm, heart and adipose tissue. (4) The clearance of triacylglycerols from chylomicrons exhibited two t 1/2 values of about 0.6 and 6.9 min in rats fed the beef tallow diet. Benfluorex did not significantly alter these values. (5) Benfluorex did not significantly alter the rate of appearance of triacylglycerol in the blood of rats injected with Triton WR 1339 to block triacylglycerol uptake. It did, however, decrease the rise in circulating glucose which presumably resulted from the stress of the procedure. (6) Benfluorex decreased the extent and duration of the rise in serum corticosterone when rats maintained on the corn oil diet were fed acutely with fructose. It also decreased the circulating concentrations of glycerol, triacylglycerol and glucose after fructose feeding. (7) Rats fed on the corn oil diet and then treated with benfluorex had lower concentrations of circulating glucose, triacylglycerol, glycerol and fatty acids after being injected with 2-deoxyglucose. (8) It is proposed that some of the long-term hypoglycaemic and hypotriglyceridaemic effects of benfluorex could be mediated indirectly through changes in endocrine balance, perhaps via the serotonergic system and in particular, by decreasing the effects of stress hormones relative to insulin. The implications of these findings are discussed in relation to controlling metabolism in stress conditions and for the management of obesity, diabetes and atherosclerosis.

Animals↗

Randomized neutron dose searching study for malignant gliomas of the brain: results of an RTOG study. Radiation Therapy Oncology Group.

From September 1980 through January 1985, the Radiation Therapy Oncology Group (RTOG) conducted a randomized, dose-searching study testing the efficacy of a concomitant neutron boost along with whole brain photon irradiation in the treatment of malignant gliomas of the brain. Patients had to have biopsy-proven, supratentorial, anaplastic astrocytoma or glioblastoma multiforme (Nelson schema) to be eligible for the study. The whole brain photon irradiation was given at 1.5 Gy per treatment, 5 days-a-week to a total dose of 45 Gy. Two days-a-week the patients were to receive neutron boost irradiation to the tumor volume as determined on CT scans. The neutron irradiation was to be given prior to and within 3 hours of the photon irradiation on that day. The rationale for this particular treatment regime is discussed. A total of 190 evaluable patients were randomized among 6 different neutron dose levels: 3.6, 4.2, 4.8, 5.2, 5.6 and 6.0 Gyn gamma. There was no difference in overall survival among the 6 different dose levels, but for patients having less aggressive tumor histology (anaplastic astrocytoma), there was a suggestion that patients on the higher dose levels had poorer overall survival than patients on the lower dose levels and also did worse than historical photon controls. Important prognostic factors were identified using a Cox stepwise regression analysis. Tumor histology, Karnofsky performance status, and patient age were found to be related to survival while extent of surgery and neutron dose had no significant impact. Autopsies were performed on 35 patients and the results correlated with the actual neutron dose as determined by central-axis isodose calculations. At all dose levels there were some patients with both radiation damage to normal brain tissue and evidence of viable tumor. No evidence was found for a therapeutic window using this particular treatment regimen.

Astrocytoma↗