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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 289 records · Page 16Linked to original sources

Verbally administered Barthel Index as functional assessment in brain tumour patients.

OBJECTIVE: To investigate verbally administered Barthel Index as a measure of functional status in patients with high grade gliomas. BACKGROUND: Barthel Index (BI) is a performance score of activities of daily living which has been validated in patients with neurological disability. While any assessment of quality of life in brain tumour patients should include all the aspects of CNS function we concentrated on measurement of physical performance status and evaluated the role of BI as a measure of palliative effect of treatment in patients with high grade glioma undergoing radiotherapy. METHODS: BI was verbally administered on 504 occasions in 107 patients with high grade glioma. The BI scores were correlated with Karnofsky performance score (KPS), and neurological performance score (NPS) as a measure of inter-index reliability. The BI's prognostic value was assessed using actuarial survival data. RESULTS: BI was sensitive to change and reflected the degree of functional impairment. In patients with high grade glioma BI correlated with KPS, and NPS (R2 = 0.872 and 0.658 respectively). BI score was also of prognostic value in terms of survival. The median survival of patients with functional independence was 9 months with moderate disability 5 months and with severe disability 4 months. CONCLUSION: Verbally administered Barthel Index is easy to use, reliable and sensitive to change and is of prognostic value. It is a useful tool in the management of patients with gliomas, as an objective evaluation of palliative effectiveness of treatment in patients with functional disability.

Activities of Daily Living↗

Right atrial silicone catheters as angioaccess for hemodialysis with special emphasis to their complications.

Right atrial silicone catheters (RASCs) serve as temporary angioaccess in hemodialysis (HD) patients. In a retrospective study of the years 1989 to 1996 we analyzed catheter-related complications, and tried to define patients at special risk for complications. We compared our results with published data on RASCs and percutaneous catheters. In 73 patients older than 64 (mean age 76) years with severe comorbidity 109 single lumen RASCs, type Demers, were implanted. Fifty-five similar catheters implanted in 44 younger patients (mean age 53) with a comparable severe comorbidity were used as controls. In the older patients the mean indwelling time was 157 (1-995) days, median 98 days, in the younger patients 135 (1-623) days, median 61 days. Early complications that led to RASC removal within one week after implantation were kinking, formation of a narrow loop, perforation, infected hematoma, and immediate clotting. Reasons for removal of the RASC after a longer period were infection, occlusion, and dislocation. In the old age group a great proportion (40%) of patients died with functioning RASC. In the literature RASCs are superior to percutaneous (Shaldon) catheters as temporary angioaccess for HD with respect to both better longevity and fewer complications such as venous stenoses or occlusions or infections. This is in accordance with our experience. However RASCs have complications, especially in the high risk groups of diabetics and patients with malignancies.

Aged↗

A protein particle vaccine containing multiple malaria epitopes.

Ty virus-like particles consist of a single protein species that can be produced in yeast. Recombinant Ty-VLPs carrying a string of up to 15 defined cytotoxic T lymphocyte (CTL) epitopes from Plasmodium species prime protective CTL responses in mice following a single administration without adjuvant. Effective processing of epitopes from the string was demonstrated in vitro and in vivo and was not affected by flanking sequences.

Amino Acid Sequence↗

Temporal bisection in humans with longer stimulus durations.

Normal adults were tested in eight temporal bisection conditions, using 500-Hz tones as stimuli. Stimulus lengths matched, or overlapped with, durations normally used in bisection experiments with animals, and chronometric counting was prevented by using a concurrent digit-shadowing task. Four experimental groups were used to investigate any effects of stimulus spacing, and stimuli were logarithmically or linearly spaced between standard "short" and "long" durations of 1 and 4, or 2 and 8 sec. A slight leftward shift of the psychophysical function was found in the logarithmic spacing condition, relative to linear spacing. Four other groups tested the conjecture that the ratio of the short and long standards might play some role in determining the location of the bisection point, and conditions with long/short ratios of 2:1 and 5:1 were used. In all cases the bisection point was close to the arithmetic mean of the short and long standards, rather than the geometric mean, as in animal studies. Overall, however, smaller long/short ratios (which may indicate more difficult temporal discriminations) produced more sensitive timing. When the long/short ratio was held constant, however, data showed nearly perfect superimposition, indicating conformity to scalar timing. In general, results were similar to those from experiments with humans that used much shorter durations, indicating the animal/human differences in bisection do not depend on the absolute lengths of the stimuli used.

Humans↗

Assessing patterns of agitation in Alzheimer's disease patients with the Cohen-Mansfield Agitation Inventory. The Alzheimer's Disease Cooperative Study.

As part of the effort of the NIA Alzheimer's disease cooperative study to develop improved instruments for quantifying effects in Alzheimer's disease (AD) clinical trials, patterns of agitated behaviors were evaluated with the Cohen-Mansfield Agitation Inventory (CMAI) in 241 AD patients and 64 healthy elderly controls with valid baseline assessment on the CMAI. The test-retest reliability of the CMAI over 1 month was good (r = 0.74 to 0.92). Physically and verbally nonaggressive behaviors were most often reported, whereas physically aggressive behaviors were rare. Frequency of agitated behaviors increased with dementia severity, especially for patients with a Mini-Mental Status Exam score of 0-4. Agitation tended to increase in the evening with dementia severity for the more impaired patients. Amount of agitation did increase after 12 months in all but controls and mildly demented patients. The CMAI shows promise for evaluating a unique aspect of behavior and may be useful in assessing the effects of cognitive enhancers and other types of psychotropic drugs on behavior in dementia patients.

Aged↗

Congenital cutis laxa and lysyl oxidase deficiency.

We report two phenotypically similar patients with primary cutis laxa associated with deficiency of lysyl oxidase, an extracellular copper enzyme the gene for which is located on chromosome 5. Previous reports of this condition have had characteristic occipital projections, abnormality of copper metabolism and X-linked inheritance. The two reported patients have no occipital projections, normal copper metabolism, Wormian bones, and a pattern of inheritance consistent with the autosomal recessive inheritance of the lysyl oxidase gene.

Child↗

Mild abnormalities in liver histology associated with chronic hepatitis: distinction from normal liver histology.

BACKGROUND: Chronic hepatitis C virus infection associated with contaminated anti-D immunoglobulin has become an issue of recent concern. The clinical course of chronic hepatitis C infection is unpredictable and histological assessment is felt to be the most reliable means of assessing disease status. Semiquantitative scoring systems have been devised, which assess degree of necroinflammatory disease activity (grade) and extent of disease progression with fibrosis (stage) in chronic hepatitis. Often, using these systems, biopsies of anti-D associated chronic hepatitis C cases show mild changes only, with low scores. The significance of these low scores is uncertain. AIMS: To evaluate the significance of low scores in chronic hepatitis. METHODS: Liver biopsies were assessed from two groups of patients in whom liver histology would be expected to be normal: 30 cases of Gilbert's syndrome and 13 necropsy cases of young people (< 45 years) with no history or risk factors for liver disease. These biopsies were scored using the histological activity index of Knodell et al and its recent modification (separation of scores for grade and stage) by Ishak et al. RESULTS: Twenty of 30 cases of Gilbert's syndrome and 11 of the 13 necropsy cases had chronic hepatitis scores of 1 or 2, whereas only eight cases of Gilbert's and two necropsy cases had scores of 0. The remaining two Gilbert's cases had scores of 3 and 5. Similar results were found using both the histological activity index of Knodell et al and the method of Ishak et al. CONCLUSION: The finding of low but positive scores using these systems in people with normal liver histology questions the reliability and significance of finding such scores in patients with chronic hepatitis and is of particular concern in the evaluation of chronic hepatitis C infection.

Adult↗

Stage-specific expression of P2Y receptors, ecto-apyrase, and ecto-5'-nucleotidase in myeloid leukocytes.

The expression of P2 purinergic receptor subtypes in leukocytes varies with both lineage and developmental stage. Given the recent identification and cloning of at least seven distinct G protein-coupled ATP receptor subtypes (P2Y family), we investigated P2Y receptor subtype expression during myeloid cell differentiation. We observed that KG-1 myeloblasts express P2Y1 but not P2Y2 receptors (previously termed P2U receptors), whereas later myeloid progenitors, including HL-60 promyelocytes and THP-1 monocytes, expressed P2Y2 but not P2Y1 receptors. In KG-1 cells, significant activation of Ca2+ mobilization by P2Y1 receptors was only observed after preincubation with potato apyrase, an exogenous ATPase. This indicated that P2Y1 receptors are desensitized in KG-1 cells by autocrine mechanisms that may involve enhanced release of endogenous nucleotides and/or decreased expression of cell-surface ecto-nucleotidases. We compared the levels of ecto-apyrase activity and expression in KG-1 myeloblasts and HL-60 promyelocytes. Extracellular ATP was rapidly metabolized by HL-60 but not by KG-1 cells. Reverse transcription-polymerase chain reaction analysis indicated that mRNA for CD39 (cluster of differentiation), an identified ecto-apyrase, was present in HL-60 but not KG-1 cells. Ecto-apyrase activity was modestly increased with differentiation of myeloid progenitors with either phorbol 12-myristate 13-acetate (PMA) or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Differentiation of HL-60 cells with PMA, but not DBcAMP, strongly induced ecto-5'-nucleotidase activity and CD73 mRNA expression. These observations indicate that signal transduction by extracellular ATP in myeloid leukocytes can be regulated by developmentally programmed changes in the expression of P2Y receptor subtypes and multiple ecto-nucleotidases.

5'-Nucleotidase↗

Using an interactive computer game to increase skill and self-efficacy regarding safer sex negotiation: field test results.

This article describes the development, field testing, and evaluation of an interactive computer program, "Life Challenge," developed by the New York State Department of Health as a tool for enhancing adolescents' sense of self-efficacy in HIV/AIDS prevention programs. The computer kiosks were field tested in 13 sites serving high-risk adolescents. The program uses a time travel adventure game format to provide information and nonthreatening skill practice. Users record and play back their responses as they "negotiate" with their chosen partners. A proof of concept evaluation with analysis of 211 audio responses found that users took negotiating tasks seriously; statistically significant learning gains were achieved on knowledge items and in self-efficacy scores (greatest improvement for those with low baseline self-efficacy levels). Challenges and problems encountered in implementing the project are described, and the potential of using computers for skill practice and educational interventions in health education is explored.

Adolescent↗

An in vitro evaluation of an automatic clamp for use with centrifugal pumps.

The risk of air emboli is a concern for all perfusionists. A new clamping device for use with centrifugal pumps is designed to clamp both the arterial and venous lines at the first indication of air or retrograde flow, thereby allowing the perfusionist to evaluate the situation and correct the problem before entraining air into the arterial pump head. After evaluating this device in our lab, we conclude that this new safety device should be added to the heart lung machine by all perfusionists using centrifugal pumps.

Cardiopulmonary Bypass↗

An in vitro comparison of gas transfer and pressure drop of the Bentley Duraflo Coated Spiral Gold and the Medtronic Carmeda Coated Maxima hollow fiber membrane oxygenators.

Two models of heparin coated, hollow fiber membrane oxygenators were tested in vitro to compare gas transfer and transoxygenator pressure drop using an established protocol. Oxygen and carbon dioxide transfer rates were measured at blood flows of 2.5 and 5.0 liters per minute with gas flow: blood flow ratios of 1:1 and 2:1 at both blood flows. All testing was performed under normothermic conditions. The data shows that oxygen transfer increases as blood flow is increased in both oxygenators. Similarly, carbon dioxide transfer is increased by both increased blood and gas flows. Finally, the pressure drop was dependent on blood flow rate alone. This study demonstrated these two oxygenators to be comparable in both oxygen and carbon dioxide transfer and also in transoxygenator pressure drop.

Animals↗

Defective neurite extension is caused by a mutation in amyloid beta/A4 (A beta) protein precursor found in familial Alzheimer's disease.

Clonal central nervous system neuronal cells, B103, do not synthesize detectable endogenous APP or APLP. B103 cells transfected with both wild-type (B103/APP) and mutant APP construct (B103/APP delta NL) secreted comparable amounts of soluble forms of APP (sAPP). B103/APP cells produced sAPP and cleaved at amyloid beta/A4 (A beta) 16, the alpha-secretase site, and B103/APP delta NL cells produced sAPP beta cleaved at A beta 1, the beta-secretase site. B103/APP delta NL cells developed fewer neurites than B103/APP cells in a serum-free defined medium. Neurite numbers of parent B103 cells were increased by the 50% conditioned medium (CM) from B103/APP cells but reduced by the CM from B103/APP delta NL cells. Chemically synthesized A beta at concentration levels higher than 1 nM reduced numbers of neurites from B103 or B103/APP delta NL cells. However, A beta at 1-100 nM could not reduce the neurite number of B103/APP cells. The protective activity against A beta's deleterious effect to reduce neurite numbers was attributed to sAPP alpha in the CM. Although sAPP alpha could block the effect of A beta, sAPP beta could not do so under the identical condition, suggesting the importance of the C-terminal 15-amino acid sequence in sAPP alpha. Nevertheless, sAPP alpha's protective activity required the N-terminal sequence around RERMS, previously identified to be the active domain of sAPP beta. The overall effect of APP mutation which overproduced A beta and sAPP beta and underproduced sAPP alpha was a marked decline in the neurotrophic effect of APP. We suggest that the disruption of balance between the detrimental effect of A beta and the trophic effect of sAPP may be important in the pathogenesis of AD caused by this pathogenic APP mutation.

Alzheimer Disease↗

The extensor digitorum brevis manus. A case report.

A case of a soft tissue mass of the dorsum of right hand in a 25-year-old, right-handed male is described. The preoperative diagnosis was a ganglion. On exploration the mass was found to be an atavistic extensor digitorum brevis manus replacing the extensor indicts proprius tendon. Division of the extensor retinaculum resulted in improvement of the symptoms. This muscle has been encountered rarely and few cases have been reported in the literature. It presents as a mass on the dorsum of the wrist. The symptoms are pain after activity. It is nearly always diagnosed as a ganglion preoperatively. The authors conclude that extensor digitorum brevis manus muscle should be included in the differential diagnosis of soft tissue tumors of dorsum of hand. Symptomatic patients are treated by division of the extensor retinaculum.

Adult↗

Three-dimensional dosimetry for intralesional radionuclide therapy using mathematical modeling and multimodality imaging.

UNLABELLED: A method of dosimetry is described that quantifies the three-dimensional absorbed-dose distribution resulting from an intralesional administration of a radiolabeled monoclonal antibody, allowing for both spatial and temporal heterogeneity of distribution of the radionuclide and without the need for a calibration scan. METHODS: A mathematical model was developed to describe the distribution of activity as a function of time resulting from infusion at a single point within the solid component of a tumor. The parameters required for this model are either known directly or may be obtained from SPECT image data registered to computed tomography. Convolution of this distribution with a point-source dose kernel enabled the three-dimensional absorbed-dose distribution to be obtained. RESULTS: This method was applied to a set of patient data acquired in the course of a clinical study performed at our center, and dose profiles and dose-volume histograms were produced. It was shown that the three-dimensional distribution of dose was significantly nonuniform. CONCLUSION: Initial results suggest that this method offers a means of determining the absorbed dose distribution within a tumor resulting from intralesional infusion. This method extends the Medical Internal Radiation Dose computation, which, in these circumstances, would make erroneous assumptions. Furthermore, it will enable individual patient treatment planning and optimization of the parameters that are within the clinician's control.

Humans↗

An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

We developed a set of informant-based items describing performance of activities of daily living (ADL) by patients with Alzheimer's disease (AD) to identify which ADL are useful for assessment of patients in clinical trials. Evaluation of ADL is an important outcome measure in AD clinical trials. For clinical trial measurement, ADL should have broad applicability, good test-retest reliability, scaling to cover a range of performance, and sensitivity to detect change in disease progression. A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer's Disease Cooperative Study Instrument protocol. Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months. Controls performed virtually all ADL items optimally at baseline and at 12 months. Among subjects with AD, 27 of the 45 ADL were widely applicable, i.e., performed at baseline or premorbidly by > 90% of subjects; showed good test-retest reliability between baseline and 1 and 2 months; correlated with MMSE scores of AD patients cross-sectionally; and showed a decline in performance from baseline to 12 months in at least 20% of AD patients. ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE. The remaining 18 ADL included several that may be useful for trials that target specific populations, e.g., women with AD. Because change on specific items depends on baseline MMSE, ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial.

Activities of Daily Living↗

A longitudinal study of behavioral pathology across five levels of dementia severity in Alzheimer's disease: the CERAD Behavior Rating Scale for Dementia. The Alzheimer's Disease Cooperative Study.

As part of the Alzheimer's Disease Cooperative Study (ADCS) Instrument Development Project, the CERAD Behavior Rating Scale for Dementia (BRSD) was examined for its sensitivity to degree of cognitive impairment, its test-retest reliability, and its sensitivity to longitudinal change. Sixty-four normal elderly participants and 261 patients with AD stratified into severity groups based on Mini-Mental State Exam (MMSE) scores were rated on the BRSD at baseline and 12-month follow-up visits. A subset of subjects was evaluated at a 1-month follow-up visit. Baseline BRSD Total Score discriminated the normal group from each AD group, and mean Total Score significantly increased with increasing dementia severity. Test-retest reliability between baseline and 1-month Total Scores was satisfactory for all AD groups. Longitudinal change was evaluated by 12-month change scores, which were significant in only the normal and in one AD group. From the results, we argue that the value of behavioral pathology assessment in clinical trials would be enhanced if additive scores were based on groups of correlated items rather than on a broad array of behaviors, some of which may increase and others may decrease in frequency as AD progresses.

Aged↗