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Biomedical subjects

S M Paul

Publications and source records attributed to S M Paul.

At least 37 records · Page 2Linked to original sources
PubMed2001

Symptom clusters and their effect on the functional status of patients with cancer.

PURPOSE/OBJECTIVES: To determine the effect of the symptom cluster of pain, fatigue, and sleep insufficiency on functional status during three cycles of chemotherapy. DESIGN: Prospective, longitudinal. SETTING: 23 outpatient offices and clinics. SAMPLE: 93 patients with cancer. The typical participant was female (72%), married/partnered (65%), white (87%), and middle-aged (55.4 years), with an average of 14.8 years of education. METHODS: The Quality of Life-Cancer (QOL-CA) version instrument and the Karnofsky Performance Scale (KPS) were completed by 93 outpatients receiving chemotherapy at baseline (Time 1) and at the end of the third cycle (Time 2). Three items (pain, tires easily, sleeps enough to meet needs) from the QOL-CA questionnaire were used to measure the symptom cluster. MAIN RESEARCH VARIABLES: Symptom cluster, outcome, functional status, chemotherapy. FINDINGS: A hierarchical multiple regression model explained 48.4% of the variance in functional status. The KPS at Time 1 explained 30.8% of the variance in KPS at Time 2 (p < 0.001). After KPS at Time 1 was partialled out from KPS at Time 2, the four independent variables entered in the next step were considered predictors of the change in functional status between Time 1 and Time 2. Age explained 11.8% of the change (p = 0.001), pain explained 10.7% of the change (p = 0.002), and fatigue explained 7.3% of the change (p = 0.011). Sleep insufficiency statistically was not significant, only explaining 1% of the change (p = 0.344). CONCLUSION: This study provides beginning insights into the effect of a symptom cluster on patients' functional status. IMPLICATIONS FOR NURSING PRACTICE: Healthcare professionals need to be aware of the presence of symptom clusters and their possible synergistic adverse effect on patients' future morbidity.

Antineoplastic Agents↗
PubMed2000

Association of an interleukin 1 alpha polymorphism with Alzheimer's disease.

BACKGROUND: Retrospective epidemiologic studies suggest that individuals exposed to anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs have a lower probability of developing AD as well as an older age at onset for the illness. Neuroinflammation may play an important role in the pathogenesis of AD. Interleukin 1 (IL-1), a potent proinflammatory cytokine, is colocalized immunohistochemically to neuritic plaques, a requisite neuropathologic feature for AD. A polymorphism in the 5'-flanking regulatory region at -889 of the IL-1 alpha gene (a C-to-T transition designated as IL-1A[-889] allele 2) may cause an overexpression of IL-1 alpha, a finding shown to be associated with inflammatory diseases. The IL-1A(-889) allele 2 polymorphism may be associated with AD pathogenesis. METHODS: A total of 259 patients with AD and 192 nondemented control subjects were included from two different centers (Indianapolis, IN, and Munich, Germany). Genotyping for APOE alleles and IL-1A(-889) allele 2 was performed by PCR-based amplification followed by restrictive endonuclease digestion. Statistical analyses were conducted by center-, gender group-, and age group-stratified Mantel-Haenszel odds ratios, CI, and p values. RESULTS: The allele frequency of IL-1A(-889) allele 2 was 46% in clinically diagnosed patients with probable AD versus 34% in control subjects from the combined centers. CONCLUSION: The authors found an increased risk for AD with an estimated Mantel-Haenszel odds ratio of 1.68 (95% CI 1.1 to 2.6; p = 0.022) for heterozygous carriers and 7.2 (95% CI 2.0 to 24.5; p = 0.003) for individuals homozygous for IL-1A(-889) allele 2. They found no evidence for an interaction between the IL-1A and the apoE epsilon 4 polymorphisms (carriers and homozygotes), age, or gender with regard to conferred risk. The data strongly support an association between the IL-1A(-889) allele 2, especially in homozygotes, and later-onset AD.

Aged↗
PubMed2000

Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease.

Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon4 > epsilon3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-beta (Abeta) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Abeta deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Abeta deposition also occurred in APP(V717F) TG, apoE(-/-) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Abeta deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.

Alzheimer Disease↗
PubMed2000

Behavioral deficits in APP(V717F) transgenic mice deficient for the apolipoprotein E gene.

Both the beta-amyloid precursor protein (APP) and the apoliprotein E (apoE) genes are involved in the pathogenesis of Alzheimer's disease (AD). We previously showed that mice over-expressing a human mutated form of APP (APP(V717F)) display age-dependent recognition memory deficits associated with the progression of amyloid deposition. Here, we asked whether 10- to 12-month-old APP(V717F) mice lacking the apoE gene, which do not present obvious amyloid deposition, differ from APP(V717F) mice in the object recognition task. The recognition performance is decreased in both transgenic mouse groups compared to control groups. Moreover, some behavioral disturbances displayed by APP mice lacking apoE are even more pronounced than those of APP mice expressing apoE. Our results suggest that the recognition memory deficits are related to high levels of soluble Abeta rather than to amyloid deposits.

Amyloid↗
PubMed2000

Alpha2 macroglobulin and the risk of Alzheimer's disease.

BACKGROUND: alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56). METHODS: We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism. RESULTS: We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors. CONCLUSIONS: Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.

Aged↗
PubMed2000

Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice.

Histological analyses were performed on the brains of APP(V717F) transgenic (Tg)mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the APP(V717F) transgene and independent of amyloid deposition.

Age Factors↗
PubMed2000

Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.

Apolipoprotein E (apoE) has been implicated as a risk factor for Alzheimer's disease and in the deposition, fibrillogenesis, and clearance of the amyloid beta-peptide (Abeta). To examine the in vivo interactions between apoE and Abeta deposition, we examined 12-month-old transgenic (tg) mice expressing human amyloid precursor protein (APP) with the V717F mutation (APP(V717F) homozygous) on an APOE null background. Elimination of APOE resulted in a redistribution and alteration in the character of Abeta deposition in homozygous APP(V717F) tg mice, with a dramatic reduction in cortical and dentate gyrus deposition, prominent increase in diffuse CA1 and CA3 deposition, and prevention of the formation of thioflavin-S-positive deposits. These alterations in Abeta deposition were not mediated by significant changes in regional APP expression, low-density lipoprotein receptor-related protein expression, or soluble Abeta levels. Thus, apoE in APP(V717F) tg mice not only affects the amount and form of Abeta deposition, but also the anatomical distribution of diffuse Abeta deposits. The APP(V717F) tg mouse can serve as a model to investigate genetic influences on the vulnerability of specific neuroanatomical regions to Abeta deposition.

Amyloid beta-Peptides↗
PubMed2000

Physical functioning and health-related quality-of-life changes with exercise training in hemodialysis patients.

The Renal Exercise Demonstration Project was designed to test the effects of two different approaches to exercise programming on the levels of physical activity, physical functioning, and self-reported health status in hemodialysis patients. Two hundred eighty-six patients were recruited for participation. Intervention patients were given individually prescribed exercise for 8 weeks of independent home exercise, followed by 8 weeks of incenter cycling during dialysis. Physical performance testing was performed at baseline and after each intervention using gait speed, sit-to-stand test, and 6-minute walk. The Medical Outcomes Study Short Form 36-item (SF-36) questionnaire was used to assess self-reported health status. The intervention group showed increased participation in physical activity. There were significant differences between the intervention and nonintervention groups in change over time in normal and fast gait speed, sit-to-stand test scores, and the physical scales on the SF-36, including the physical component scale. The intervention group improved in these test results, whereas the nonintervention group either did not change or declined over the duration of the study. It is clear that improvements in physical functioning result from exercise counseling and encouragement in hemodialysis patients. Because self-reported physical functioning is highly predictive of outcomes in hemodialysis patients, more attention to patients' levels of physical activity is warranted.

Activities of Daily Living↗
PubMed2000

Overexpression of the neuritotrophic cytokine S100beta precedes the appearance of neuritic beta-amyloid plaques in APPV717F mice.

Homozygous APPV717F transgenic mice overexpress a human beta-amyloid precursor protein (betaAPP) minigene encoding a familial Alzheimer's disease mutation. These mice develop Alzheimer-type neuritic beta-amyloid plaques surrounded by astrocytes. S100beta is an astrocyte-derived cytokine that promotes neurite growth and promotes excessive expression of betaAPP. S100beta overexpression in Alzheimer's disease correlates with the proliferation of betaAPP-immunoreactive neurites in beta-amyloid plaques. We found age-related increases in tissue levels of both betaAPP and S100beta mRNA in transgenic mice. Neuronal betaAPP overexpression was found in cell somas in young mice, whereas older mice showed betaAPP overexpression in dystrophic neurites in plaques. These age-related changes were accompanied by progressive increases in S100beta expression, as determined by S100beta load (percent immunoreactive area). These increases were evident as early as 1 and 2 months of age, months before the appearance of beta-amyloid deposits in these mice. Such precocious astrocyte activation and S100beta overexpression are similar to our earlier findings in Down's syndrome. Accelerated age-related overexpression of S100beta may interact with age-associated overexpression of mutant betaAPP in transgenic mice to promote development of Alzheimer-like neuropathological changes.

Aging↗
PubMed2000

Low-functioning hemodialysis patients improve with exercise training.

The Renal Exercise Demonstration Project provided two different approaches to exercise programming to a group of hemodialysis patients. Physical functioning and self-reported health-related quality of life were measured at baseline, after 2 months of independent exercise, and again after 2 months of in-center cycling. This study compares the responses to intervention of patients who initially scored low (<34) on the Physical Component Scale (PCS) on the Medical Outcomes Study Short-Form 36 questionnaire to those who initially scored higher (>34) on the same scale. The high-PCS group scored higher on all physical function tests (normal gait speed, fast gait speed, and sit-to-stand test) at each testing time than the low-PCS group. The high-PCS group improved only on the sit-to-stand test, whereas the low-PCS group improved in all three physical function tests. There were significant differences between the groups in change over time in all the physical scales and the PCS over time, with the low-PCS group showing improvements in response to the intervention and the high-PCS group showing no change over time. No differences in change over time were noted between the groups on the mental scales in either group. We conclude that low-functioning hemodialysis patients can benefit from exercise counseling in both objective measures of physical functioning and self-reported physical functioning. The impact of such interventions seems to be more profound in the lowest functioning patients.

Analysis of Variance↗
PubMed2000

Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy-induced mucositis.

OBJECTIVE: To test the effectiveness of 3 mouthwashes used to treat chemotherapy-induced mucositis. The mouthwashes were as follows: salt and soda, chlorhexidine, and "magic" mouthwash (lidocaine, Benadryl, and Maalox). STUDY DESIGN: A randomized, double-blind clinical trial was implemented in 23 outpatient and office settings. Participants were monitored from the time they developed mucositis until cessation of the signs and symptoms of mucositis, or until they finished their 12-day supply of mouthwash. All participants followed a prescribed oral hygiene program and were randomly assigned a mouthwash. Nurses used the Oral Assessment Guide for initial assessment and taught patients how to assess their own mouths, then phoned the patients every other day to gather status reports. RESULTS: In 142 of 200 patients, there was a cessation of the signs and symptoms of mucositis within 12 days. No significant differences in time for the cessation of the signs and symptoms were observed among the 3 groups. CONCLUSIONS: Given the comparable effectiveness of the mouthwashes, the least costly was salt and soda mouthwash.

Aluminum Hydroxide↗
PubMed2000

Modulation of A beta deposition in APP transgenic mice by an apolipoprotein E null background.

Several lines of evidence implicate apolipoprotein E (apoE) and its receptor--the low density lipoprotein receptor related protein (LRP)--in Alzheimer's disease (AD) pathogenesis, including increased amyloid deposition in human AD brains of people containing the apoE epsilon 4 allele, presence of apoE and LRP in amyloid plaques, and in vitro uptake of amyloid precursor protein (APP) and amyloid beta protein (A beta) by LRP. Studies of crosses of apoE knockout mice with APP transgenic mice support a complex interaction between apoE and A beta deposition. In the Tg2576 mice expressing human APPK670N-M671L, apoE determines the amount, morphology, vascular pattern, and neuropil response to A beta deposits. In the PDAPP mice expressing human APPV717F, apoE also affects the anatomical localization of cerebral A beta deposits. Thus, APP transgenic mice can serve as models to investigate genetic influences on the amount and timing of cerebral amyloidosis, the morphology of amyloid plaques, and the vulnerability of specific neuroanatomical regions to A beta deposition.

Alzheimer Disease↗
PubMed2000

HIV disease surveillance: medicine and public health working together.

Public health surveillance is critical to the management of the HIV epidemic. Surveillance helps to define changing trends, formulate and strategically implement preventive initiatives, and evaluate the effectiveness of interventions. Collaboration between clinical medicine and public health is essential to reliable surveillance.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model.

The epsilon4 allele of apolipoprotein E (ApoE) is an important genetic risk factor for Alzheimer's disease (AD). Increasing evidence suggests that this association may be linked to the ability of ApoE to interact with the amyloid-beta (Abeta) peptide and influence its concentration and structure. To determine the effect of ApoE on Abeta and other AD pathology in vivo, we used APPsw transgenic mice and ApoE knockout (-/-) mice to generate APPsw animals that carried two (ApoE +/+), one (ApoE +/-), or no copies (ApoE -/-) of the normal mouse ApoE gene. At 12 months of age, Abeta deposition was present in the cortex and hippocampus and was also prominent within leptomeningeal and cortical blood vessels of all APPsw ApoE +/+ mice. Importantly, although Abeta deposition still occurred in APPsw ApoE -/- mice, no fibrillar Abeta deposits were detected in the brain parenchyma or cerebrovasculature. There was also no neuritic degeneration associated with Abeta deposition in the absence of ApoE. These data demonstrate that ApoE facilitates the formation of both neuritic and cerebrovascular plaques, which are pathological hallmarks of AD and cerebral amyloid angiopathy.

Alzheimer Disease↗
PubMed2000

HIV resistance testing: a new clinical tool.

Drug resistance threatens to erase the recent gains made in treating HIV infection. HIV resistance testing offers clinicians the ability to screen patients for resistant strains and adjust treatment accordingly. Resistance testing is recommended for patients on antiretroviral agents with virologic failure or with suboptimal suppression of viral load after initiation of antiretroviral therapy. Because of the potential transmission of resistant strains, testing should be considered for patients with acute infection. Although the care of many AIDS patients is complex and should be managed by a physician with experience and expertise in HIV disease, all practitioners should be familiar with the types of testing available and their limitations.

Anti-HIV Agents↗