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Biomedical subjects

L W Thompson

Publications and source records attributed to L W Thompson.

At least 19 recordsLinked to original sources

Well-being, appraisal, and coping in Latina and Caucasian female dementia caregivers: findings from the REACH study.

While there has been considerable interest in studying ethnically diverse family caregivers, few studies have investigated the influence of dementia caregiving on Latino families. The current study includes participants from two sites of the REACH (Resources for Enhancing Alzheimer's Caregiver Health) project to compare well-being, appraisal, and religiosity by ethnicity, with specific attention to levels of acculturation. Latina (n = 191) and Caucasian female (n = 229) dementia family caregivers from two regions of the United States (Miami, Florida and Northern California) were compared at baseline on demographics, care recipient characteristics, mental and physical health, and psychosocial resources, including appraisal style and religiosity. Latina caregivers reported lower appraisals of stress, greater perceived benefits of caregiving, and greater use of religious coping than Caucasian caregivers. The relationship of these variables to level of acculturation for the Latina caregivers was also explored. Implications of these results for psychosocial interventions with Latino and Caucasian family caregivers are discussed.

Adaptation, Psychological↗

A comparison of marital interaction patterns between couples in which the husband does or does not have Alzheimer's disease.

UNLABELLED: Objectives. Our main purpose was to examine similarities and differences in patterns of interpersonal interaction between Alzheimer's disease (AD) caregiving and noncaregiving couples (n = 54). Methods. Twenty-seven wives caring for moderately impaired husbands with probable AD and 27 noncaregiving wives from comparable sociodemographic backgrounds were videotaped in their homes during both mealtime and a future event planning task. In addition, they completed self-report questionnaires to assess depression, stress, relationship mutuality, and perceived hope. Results. Compared with their counterparts, caregiving wives reported higher levels of depression and stress, but similar shared values and closeness. For the three factors developed from the Marital Interaction Coding System (MICS, version IV; Supportive Facilitative, and Rapport Building), a complex pattern of results was found in which disease status, type of task, and gender interacted significantly. Noncaregiving couples were more interactive overall and expressed more support to each other. Caregiving wives were found to be most facilitative during the planning task, whereas AD husbands were highest on interactions that built rapport (e.g., smiling) during that same task. Caregiving wives actually increased their facilitative behavior from the mealtime to planning task, probably reflecting the increased demand characteristics of the latter. DISCUSSION: This study is one of a small body of literature to describe the negative impact of AD on spousal communication as observed and coded in two videotaped interaction situations in the home. Suggestions are made for future research, including the inclusion of longitudinal designs and non-Caucasian couples.

Adaptation, Psychological↗

Comparison of desipramine and cognitive/behavioral therapy in the treatment of elderly outpatients with mild-to-moderate depression.

The authors evaluated the efficacy of desipramine-alone, vs. cognitive/behavioral therapy-alone (CBT) vs. a combination of the two, for the treatment of depression in older adult outpatients. Patients (N=102) meeting criteria for major depressive disorder were randomly assigned to one of these three treatments for 16 to 20 therapy sessions. All treatments resulted in substantial improvement. In general, the CBT-Alone and Combined groups had similar levels of improvement. In most analyses, the Combined group showed greater improvement than the Desipramine-Alone group, whereas the CBT-Alone group showed only marginally better improvement. The combined therapies were most effective in patients who were more severely depressed, particularly when desipramine was at or above recommended stable dosage levels. The results indicate that psychotherapy can be an effective treatment for older adult outpatients with moderate levels of depression.

Aged↗

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↗

Vaccination for melanoma.

Our knowledge of the immune system has grown tremendously in the 50 years since Coley used bacteria in an attempt to create a vaccine for cancer. The strategy for cancer vaccines has developed in that time as well. Both clinical and laboratory evidence suggests that melanoma is the more immunogenic of solid tumors. If treated early, melanoma can be controlled with surgery, but many patients continue to die from it. With our increased understanding of the immune system's interaction with melanoma, many clinical trials of melanoma vaccines are now underway. Vaccines designed to treat metastatic melanoma have shown some evidence of clinical effectiveness. This article outlines the current status of melanoma vaccination.

Antigens, Neoplasm↗

Melanoma vaccines.

Remarkable advances in tumor vaccination have been made since Coley first deliberately infected cancer patients with both live and heat-killed bacteria. Melanoma is the most immunogenic solid tumor and, as such, has served as the major model for tumor vaccine investigation in both the laboratory and the clinic. Many advances in the field of melanoma vaccination have been based on an improved understanding of the cellular interaction required to induce a specific antitumor immune response. As a result of this new knowledge, many clinical trials of melanoma vaccines are now under way, and vaccines for metastatic melanoma have shown evidence of clinical effectiveness. This paper outlines the current status of melanoma vaccination.

Cancer Vaccines↗

Terminal modifications inhibit proteolytic degradation of an immunogenic MART-1(27-35) peptide: implications for peptide vaccines.

Peptide epitopes for tumor-reactive cytotoxic T-lymphocytes (CTL) have been identified on human cancers and are being used in tumor vaccine trials. However, the pharmacokinetics and pharmacodynamics of such peptides have been inadequately studied. It is predicted that immunogenic tumor peptides would have short half-lives in vivo. The goal of the present work was to evaluate the stability of the immunogenic peptide MART-1(27-35) in fresh normal human plasma (NHP) and to identify modifications that convey protection against enzymatic destruction without loss of immunogenicity. We evaluated the stability of the MART-1(27-35) peptide (AAGIGILTV) and modified forms of that peptide for stability and immune recognition in an in vitro model. The peptides were incubated in plasma for varied time intervals and evaluated for their ability to reconstitute the epitope for MART-1(27-35)-reactive CTL. Loss of CTL reactivity signaled loss of immunoreactive peptide. When 1 microM MART-1(27-35) peptide was incubated in plasma prior to pulsing on target cells, CTL reactivity was lost within 3 hr, and the calculated half-life of this peptide was 22 sec. This degradation was mediated by peptidases. The stability of MART-1(27-35) was markedly prolonged by C-terminal amidation and/or N-terminal acetylation (peptide capping), or by polyethylene-glycol modification (PEGylation) of the C-terminus. These modified peptides were recognized by CTL. The MART-1(27-35) peptide is very unstable in plasma. It is probable that it and other immunogenic peptides will be similarly unstable in vivo. Immunogenicity of these peptides might be enhanced by creating modifications that enhance stability.

Antigens, Neoplasm↗

Physical and psychosocial correlates of hormone replacement therapy with chronically stressed postmenopausal women.

OBJECTIVES: This study investigated the relationship between hormone replacement therapy (HRT) use and physical and psychosocial functioning in a sample of chronically stressed older women. METHODS: Participants (N = 94) were postmenopausal women caring for a parent or spouse with dementia. Caregivers were evaluated using both psychological and physical health indices. RESULTS: Caregivers receiving HRT reported lower levels of hostility and were less likely to report unpleasant interactions with members of their support network; these findings were unrelated to demographic variables, caregiving-related indices, or health behaviors. HRT recipients had lower 10-year risk scores for cardiovascular disease, but there were no group differences in stroke risk. The largest effects on hostility, depression, heart and stroke risk were observed in caregivers receiving a combination of estradiol and progesterone. DISCUSSION: HRT for postmenopausal women may promote positive outcomes for some, but not for all, affective states and cardiovascular variables vulnerable to chronic life stressors.

Aged↗

Human melanoma patients recognize an HLA-A1-restricted CTL epitope from tyrosinase containing two cysteine residues: implications for tumor vaccine development.

To identify shared epitopes for melanoma-reactive CTL restricted by MHC molecules other than HLA-A*0201, six human melanoma patient CTL lines expressing HLA-A1 were screened for reactivity against the melanocyte differentiation proteins Pmel-17/gp100, MART-1/Melan-A, and tyrosinase, expressed via recombinant vaccinia virus vectors. CTL from five of the six patients recognized epitopes from tyrosinase, and recognition of HLA-A1+ target cells was strongly correlated with tyrosinase expression. Restriction by HLA-A1 was further demonstrated for two of those tyrosinase-reactive CTL lines. Screening of 119 synthetic tyrosinase peptides with the HLA-A1 binding motif demonstrated that nonamer, decamer, and dodecamer peptides containing the sequence KCDICTDEY (residues 243-251) all reconstituted the CTL epitope in vitro. Epitope reconstitution in vitro required high concentrations of these peptides, which was hypothesized to be a result of spontaneous modification of cysteine residues, interfering with MHC binding. Substitution of serine or alanine for the more N-terminal cysteine prevented modification at that residue and permitted target cell sensitization at peptide concentrations 2 to 3 orders of magnitude lower than that required for the wild-type peptide. Because spontaneous modification of sulfhydryl groups may also occur in vivo, tumor vaccines using this or other cysteine-containing peptides may be improved by amino acid substitutions at cysteine residues.

Alanine↗

No association between the alpha 1-antichymotrypsin A allele and Alzheimer's disease.

The alpha 1-antichymotrypsin (ACT) A allele was recently associated with Alzheimer's disease (AD), and the ACT AA genotype was reported to be more frequent in AD subjects with the apolipoprotein E (APOE) epsilon4 allele. We examined ACT and APOE genotypes in a sample of 160 subjects with probable AD and in 102 elderly control subjects. ACT A allele frequencies were similar in AD subjects (0.503) and elderly controls (0.519). In addition, we found no evidence that in AD the AA genotype is more frequent in subjects with the APOE epsilon4 allele than in those without it. Our results do not support an association between the ACT A allele and AD.

Adult↗

Cognitive-behavioral therapy and treatment for late-life depression.

Cognitive-behavioral therapy is a brief psychotherapy stemming from a model that emphasizes the importance of distorted thoughts and the lack of pleasurable activities in the development of affective disorders. The focus of the therapy can be on either eliminating distorted thought systems or increasing the number of pleasant events that occur on a daily basis, or both. The highly structured therapy presents various skills for patients to learn through class exercises and homework assignments. Older adults respond well to cognitive-behavioral therapy, reporting that they appreciate the structure and the opportunity to learn skills that can help when they are confronted with new stresses. Many also like the focus on here-and-now problems rather than the past. A few treatment modifications are necessary to accommodate community elders complaining of depression. Generally, information must be presented more slowly, taking advantage of multiple modes of presentation. To maintain an active learning process, elder patients should be asked frequently to summarize the material being presented. They should also be given handouts of complex materials and encouraged to maintain notebooks. Other modifications may be required for special populations of older patients.

Age Factors↗

Effects of a music therapy strategy on depressed older adults.

A music-facilitated psychoeducational strategy was developed as a cost-effective and accessible intervention for older adults experiencing symptoms of depression, distress, and anxiety. Thirty older adults who had been diagnosed with major or minor depressive disorder were randomly assigned to one of three 8-week conditions: (1) a home-based program where participants learned music listening stress reduction techniques at weekly home visits by a music therapist; (2) a self-administered program where participants applied these same techniques with moderate therapist intervention (a weekly telephone call); or (3) a wait list control. Participants in both music conditions performed significantly better than the controls on standardized tests of depression, distress, self-esteem, and mood. These improvements were clinically significant and maintained over a 9-month follow-up period. The potential for this type of intervention with homebound elders and others who have limited access to services is discussed.

Affect↗

Verbal learning and/or memory improves with glycemic control in older subjects with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To determine whether cognitive function improves with improved glycemic control in older subjects with non-insulin-dependent diabetes (NIDDM). We hypothesized that with improved glycemic control: 1) learning and memory, 2) attention, and 3) complex perceptual-motor function would improve, but that 4) simple perceptual-motor function would not. DESIGN: Non-randomized control trial. SETTING: Aging Study Unit, Department of Veterans Affairs Medical Center. SUBJECTS: Thirty subjects with NIDDM; 17 on oral hypoglycemic agents; 13 untreated at study entry. Thirteen normal controls. INTERVENTION: Subjects on oral hypoglycemic agents were taken off medications. After 1 month, they and previously untreated subjects began treatment with glipizide. Dose was titrated up weekly until fasting plasma glucose was less than 7.8 mmol/L or maximal dose (40 mg/day). Controls received no medication. MEASUREMENTS: Fasting plasma glucose (FPG), glycated hemoglobin, and measures of cognitive function in four general categories: 1) learning and memory, 2) ability to sustain attention, 3) complex perceptual-motor function, and 4) simple perceptual-motor function. All were evaluated in subjects with NIDDM at baseline (T1), after 1-month washout (T2), and after 2 (T3) and 4 months (T4) of optimal glycemic control or maximal dose. Controls were evaluated at the same intervals. RESULTS: FPG and glycated hemoglobin rose in previously treated subjects from T1 to T2 (9.4 +/- SEM 0.4 to 14.7 +/- 0.7 mmol/L and 10.9 +/- 0.7% to 12.2 +/- 0.6%, respectively) but were unchanged in previously untreated subjects (11.3 +/- 0.6 to 11.8 +/- 0.9 mmol/L and 10.9 +/- 0.7% to 11.7 +/- 0.7%). With glipizide treatment, there was a decrease in FPG level at T3 (9.4 +/- 0.5 mmol/L in previously treated, 6.9 +/- 0.4 mmol/L in previously untreated), which persisted at T4. Glycated hemoglobin fell similarly. FPG and glycated hemoglobin were unchanged in controls. As hypothesized, learning and memory improved over time with treatment in both groups of subjects but was unchanged in controls (P < 0.05). Detailed analysis indicated that the improvement occurred primarily in the learning of verbal material. Contrary to hypothesis, attention and complex perceptual-motor function did not show improvement. As expected, simple perceptual-motor function did not show any improvement with treatment. CONCLUSIONS: The results are consistent with previous findings that poor glycemic control in older subjects with NIDDM is associated with decreased cognitive functioning, and suggest that verbal learning and memory may improve with improved glycemic control.

Aged↗

Atenolol compared with nifedipine: effect on cognitive function and mood in elderly hypertensive patients.

OBJECTIVE: To compare the effects of atenolol and nifedipine on mood and cognitive function in elderly hypertensive patients. DESIGN: Randomized, double-blind, crossover trial. PATIENTS: Thirty-one elderly volunteers (7 women and 4 men) 60 to 81 years of age with mild to moderate hypertension were recruited from the general community and a Veterans Affairs hospital hypertension clinic. Six volunteers withdrew at early phases of the study for reasons unrelated to adverse drug effects. INTERVENTIONS: Participants had 2 weeks of placebo, to 6 weeks of titration with atenolol or nifedipine, and weeks of treatment followed by similar periods with the other drug. MEASUREMENTS: Psychometric tests designed to assess mood and cognitive function. RESULTS: In the group first treated with nifedipine, the summed recall score on the Buschke selective reminding test (a test of verbal learning and memory) decreased by 9.3 words (95% CI, 2.8 to 15.6 words), or 0%, during nifedipine treatment compared with placebo (P = 0.031). The group first treated with atenolol showed no improvement in summed recall scores when results seen during atenolol therapy and placebo administration were compared (P = 0.10); however, this group had an improvement of 16.1 words (CI, 5.6 to 26.5 words), or of 16%, when the atenolol score was compared with the nifedipine score (P = 0.026). In the group first treated with nifedipine, 6 of 11 patients 55%) showed a decrease of 5 words or more during nifedipine therapy compared with placebo, whereas only 1 of the 14 patients (7%) in the group first treated with atenolol showed a similar decrease (P less than 0.01). On the digit symbol test (a psychomotor test), patients treated first with atenolol tended to improve, whereas patients treated first with nifedipine tended to decline. The difference between nifedipine and atenolol, in terms of the change from the score seen during placebo, was 4.3 codings (CI, 0.7 to 7.9 codings) or 10% (P = 0.043). No statistically significant differences were seen between nifedipine and atenolol therapy regarding the other measures of psychomotor ability, sustained attention, motor performance, verbal fluency, or abstract reasoning, and no effects of either drug on mood or psychopathologic symptoms were noted. CONCLUSIONS: Although atenolol and nifedipine are generally free of gross effects on cognition or mood, nifedipine may subtly impair learning and memory in some elderly hypertensive patients.

Affect↗

Endogenous depression in the elderly: prevalence and agreement among measures.

This article describes agreement among diagnoses made according to five definitions of endogenous depression in a sample of 99 depressed elders and discusses the relationship among these systems and selected demographic and clinical characteristics. Poor to fair agreement was generally demonstrated, except for Research Diagnostic Criteria (Spitzer, Endicott, & Robins, 1978) and Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., rev. (American Psychiatric Association, 1987), which demonstrated excellent agreement. Mostly, demographic and clinical variables (e.g., severity of depression) were unrelated to endogeneity diagnoses. The conclusion was reached that these criteria are not all measuring the same construct in older adults and that the relationship between depression severity and endogeneity should be discussed in terms of specific definitions rather than general terms.

Aged↗

Interaction of depression and bereavement on mental health in the elderly.

Three hundred ninety-three elderly adults aged 55 and older were divided into 1 of 9 subgroups in a 3 (bereavement group: survivors of spouses who died by natural death or by suicide and nonbereaved control Ss) x 3 (depression group: none, mild, and moderate-severe) design over 4 times of measurement--1 month, 6 months, 1 year, and 2.5 years after death of spouse. Significant Bereavement x Depression Group effects were obtained on Brief Symptom Inventory scores. The moderate-severe depression/suicide subgroup had the greatest psychiatric complications with bereavement. Results indicated that elderly persons with significant clinical depression at the time of a spouse's death were at significant risk for psychological complications during the bereavement process, and survivors of spouses who had committed suicide were even more at risk within the greatest depression group.

Adaptation, Psychological↗

The effects of late-life spousal bereavement over a 30-month interval.

Self-report measures of grief, depression, and general psychopathology were studied in widows and widowers over a 2.5-year period following death of their partner. A comparison sample of men and women was also followed for the same period. Differences in severity of depression and psychopathology previously reported at 2 months postloss (Gallagher, Breckenridge, Thompson, & Peterson, 1983) diminished to nonsignificant levels at 12 and 30 months. However, significant differences between bereaved and comparison subjects on measures of grief were still apparent 30 months after spousal loss. A main effect of gender for depression and psychopathology (but not for grief) was found at 2 and 12 months: Women reported more distress than men regardless of bereavement status. Results indicate that the experience of grief persists for at least 30 months in both older men and women who have lost their spouse.

Adaptation, Psychological↗