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Changes in disability before and after myocardial infarction in older adults.

BACKGROUND: Disability in older adults is thought to occur primarily as a consequence of clinical disease episodes. However, the temporal relationship between clinical disease and disability has received little systematic attention. METHODS: Data from a prospective population-based study of 2812 older adults were analyzed to examine changes in disability before and after acute myocardial infarction. Disability outcomes included up to 9 yearly assessments of disability in activities in daily living, disability in basic physical functions, and disability in tasks requiring basic mobility and strength. RESULTS: A total of 279 myocardial infarctions occurred during 9 years of follow-up. After adjustment for age and sex, the average yearly increase in disability in activities of daily living and basic physical functions was not significantly greater in the 1-year period after myocardial infarction than in the 3-year period before myocardial infarction (P values >.20). Disability in basic mobility and strength showed a significantly greater increase in the year after myocardial infarction (P = .02). The results did not change after adjustment for comorbidity and chest pain or when restricted to incident cases of myocardial infarction or survivors. An additional exploratory analysis suggested that the rate of increase in some forms of disability may start to accelerate at about 1 year before the event, rather than after the event. CONCLUSIONS: The increase in disability after myocardial infarction may form a continuation of increases that occur before the event and challenge commonly held notions about the temporal relationship between clinical disease and disability. Changes in disability before acute disease episodes may be related to subclinical disease.

Activities of Daily Living↗

Impact of chronic kidney disease on health-related quality-of-life improvement after coronary artery bypass surgery.

BACKGROUND: Little is known about the impact of chronic kidney disease (CKD) on health-related quality-of-life outcomes after coronary artery bypass grafting (CABG). METHODS: Our objective was to examine the changes in physical function (PF) and mental health (MH) 6 months after CABG in 1055 patients with and without CKD. The primary end points were mean change in score and status of "improved" or "worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form 36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD stage (0-5). RESULTS: Absolute PF and MH scores at baseline and at 6 months varied by renal impairment level. Patients with severe CKD (stages 4-5) had a mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in the rest of the cohort (P<.001). After adjustment for baseline score, 21% of patients with advanced CKD experienced worsened PF scores, compared with 0% of patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores, patients with and without CKD had similar improvements in mean MH scores at 6 months, and patients with stages 4 to 5 CKD had the highest frequency of those with improved MH scores (77%). After adjustment, no patients experienced worsened MH scores. CONCLUSIONS: After 6 months, patients with severe CKD who underwent CABG had improvement in MH but not improvement in PF and may have had worsened PF compared with those without severe CKD. Comparable evidence regarding quality-of-life outcomes in the absence of CABG is needed to more fully inform decision making regarding patients with severe CKD and coronary artery disease.

Activities of Daily Living↗

Time course of depression and outcome of myocardial infarction.

BACKGROUND: Depression predicts worse outcomes after myocardial infarction (MI), but whether its time course in the month following MI has prognostic importance is unknown. Our objective was to evaluate the prognostic importance of transient, new, or persistent depression on outcomes at 6 months after MI. METHODS: In a prospective registry of acute MI (Prospective Registry Evaluating outcomes after Myocardial Infarction: Events and Recovery [PREMIER]), depressive symptoms were measured in 1873 patients with the Patient Health Questionnaire (PHQ) during hospitalization and 1 month after discharge and were classified as transient (only at baseline), new (only at 1 month), or persistent (at both times). Outcomes at 6 months included (1) all-cause rehospitalization or mortality and (2) health status (angina, physical limitation, and quality of life using the Seattle Angina Questionnaire). RESULTS: Compared with nondepressed patients, all categories of depression were associated with higher rehospitalization or mortality rates, more frequent angina, more physical limitations, and worse quality of life. The adjusted hazard ratios for rehospitalization or mortality were 1.34, 1.71, and 1.42 for transient, new, and persistent depression, respectively (all P<.05). Corresponding odds ratios were 1.62, 2.73, and 2.64 (all P<.01) for angina and 1.69, 2.25, and 3.27 (all P<.05) for physical limitation. Depressive symptoms showed a stronger association with health status compared with traditional measures of disease severity. CONCLUSION: Depressive symptoms after MI, irrespective of whether they persist, subside, or newly develop in the first month after hospitalization, are associated with worse outcomes after MI.

Activities of Daily Living↗

Depressive symptoms after acute myocardial infarction: evidence for highest rates in younger women.

BACKGROUND: Depression is common in patients hospitalized with acute myocardial infarction (AMI). In the community, younger women are uniquely prone to depression. Whether younger women are also more likely to have depression during hospitalization with AMI is unknown. METHODS: A total of 2498 AMI patients (1284 patients <or=60 years; 814 women and 1684 men) were enrolled from 19 US centers in the Prospective Registry Evaluating Outcomes After Myocardial Infarction: Events and Recovery (PREMIER) study between January 2003 and June 2004. Depression was assessed at the time of hospitalization and was defined as a Primary Care Evaluation of Mental Disorders Brief Patient Health Questionnaire (PHQ) score of 10 or higher. RESULTS: Younger (<or=60 years) patients had higher mean PHQ scores than older patients (6.4 vs 5.0; P<.001) and women had higher mean PHQ scores than men (6.8 vs 5.2; P<.001). When stratified by both age and sex, younger women had the highest PHQ scores (8.2; P<.001 for the sex-age interaction). The prevalence of depression was 40% in women 60 years or younger, 21% in women older than 60, 22% in men 60 or younger, and 15% in men older than 60. In a logistic model adjusted for study center, race, medical history, and coronary heart disease risk factors, the odds of depression for women 60 years or younger were significantly higher than for the other sex-age groups and were 3.1 times higher than the reference group of men older than 60 years. CONCLUSIONS: The prevalence of depression is high in younger women with AMI. Because depression after AMI has been associated with adverse outcomes, younger women, a high-risk group compared with men, may particularly benefit from aggressive screening and treatment of post-AMI depression.

Age Factors↗

Amyotrophic lateral sclerosis with antecedent poliomyelitis.

Histopathological and virological studies were performed on autopsy tissue from a 47-year-old man who had a history of acute poliomyelitis at age 15 years and died after a three-year course of amyotrophic lateral sclerosis (ALS). The poliovirus serologic tests suggested prior infection with poliovirus type 3 but no ongoing poliovirus infection. The CNS showed typical features of ALS with no inclusion bodies or inflammatory cells. Attempts to isolate poliovirus in the CNS were unsuccessful and results of immunofluorescence studies for poliovirus antigen were negative. Molecular hybridization experiments using a DNA copy of the complete poliovirus genome failed to demonstrate poliovirus-related RNA or DNA sequences in the CNS. These studies, using sensitive techniques, indicate that there was no evidence of the continuing presence of poliovirus in this patient with ALS and antecedent poliomyelitis.

Adolescent↗

Treatment of retinal angiomatous proliferation in age-related macular degeneration: a series of 104 cases of retinal angiomatous proliferation.

OBJECTIVE: To report the management of retinal angiomatous proliferation (RAP), a recently described intraretinal neovascular lesion occurring in age-related macular degeneration. METHODS: This was a retrospective review of consecutive patients with age-related macular degeneration who underwent treatment of RAP from January 1, 2000, through January 31, 2003. Inclusion criteria were age 55 years or older, signs of age-related macular degeneration, and diagnosis of RAP based on dynamic indocyanine green angiography. Baseline angiograms were reviewed and RAP was classified into the following 3 stages: stage 1, intraretinal neovascularization, early stage; stage 2, subretinal neovascularization, middle stage; and stage 3, choroidal neovascularization, late stage. Treatment and concomitant treatment results were assessed separately for each RAP stage. The clinical data were statistically analyzed (chi2 test and analysis of variance) for 2 main outcome measures--complete obliteration of the lesion and final visual acuity. RESULTS: Eighty-one patients (99 eyes) with 104 RAPs were identified. Forty-two lesions were at stage 1, 42 at stage 2, and 20 at stage 3. The following 5 treatments were performed: direct laser photocoagulation of the vascular lesion, laser photocoagulation of the feeder retinal arteriole, scatter "gridlike" laser photocoagulation, photodynamic therapy, and transpupillary thermotherapy. Complete obliteration of RAP was achieved in about 24 (57.1%) of the stage 1 lesions (direct laser photocoagulation of the vascular lesion, 73% success rate; photodynamic therapy, 45%), 11 (26.2%) of the stage 2 lesions (scatter gridlike laser photocoagulation, 38% success rate; direct laser photocoagulation of the vascular lesion, 17%), and only 3 (15.0%) of stage 3 lesions (P = .001). Predictive factors with a significant effect on final visual acuity were initial visual acuity (P = .003) and early lesion stage (P = .04). Best final visual acuity was 0.41 (mean, direct laser photocoagulation of the vascular lesion in stage 1) and 0.39 (mean, photodynamic therapy in stage 1), with a mean decrease of 2.5 and 3 lines from baseline, respectively. CONCLUSIONS: Treatment of RAP remains difficult. Early detection of the lesion and subsequent direct conventional laser photocoagulation seems to be associated with better anatomical and functional outcome. Once the vascular complex is well established, anatomical closure is rarely achieved. Further study is warranted to assess the long-term efficacy and the need for re-treatment.

Aged↗

Scanning laser ophthalmoscopy and angiography with a wide-field contact lens system.

OBJECTIVE: To perform fluorescein and indocyanine green angiography for large or peripheral chorioretinal structures using a contact lens system that provides a 5-fold increase in the field of view of a confocal scanning laser ophthalmoscope (SLO). METHODS: Separate handheld contact and noncontact ophthalmoscopic lenses were manually aligned with the optical axis of a confocal SLO to demonstrate the feasibility of wide-field SLO angiography. An integrated, wide-field contact lens system was then designed and constructed to increase the SLO's 10 degrees , 20 degrees , and 30 degrees imaging fields to 50 degrees , 100 degrees , and 150 degrees , respectively. RESULTS: Simultaneous fluorescein and indocyanine green angiography was performed with the integrated, wide-field contact lens system for more than 50 patients with disorders that affect their peripheral retina and choroid. Retinal and choroidal abnormalities, including neovascularization and capillary nonperfusion, are easily detected and documented well beyond the range of conventional fundus cameras and SLOs. Peripheral retinal and choroidal hemodynamics can be readily observed and recorded. CONCLUSIONS: A confocal SLO has adequate resolution for clinically useful reflectance and angiographic imaging even when its field size is increased 5-fold by a wide-field contact lens system. Dynamic and static wide-field angiography can be performed without the limitations of manual or computer-automated photomontages. Peripheral retinal conditions can be studied and recorded to confirm observations from indirect ophthalmoscopy and to facilitate retinal photocoagulation and vitreoretinal surgery.

Adult↗

Lamina puncture for central retinal vein occlusion: results of a pilot trial.

OBJECTIVE: To evaluate the effect of treatment by lamina puncture, a novel procedure to create a perivascular opening within the optic nerve head by a transvitreal approach, on visual acuity after central retinal vein occlusion (CRVO) in older patients. METHODS: The patients comprised a nonrandomized, consecutive, interventional case series of older patients being seen with CRVO. Patients 65 years or older with CRVO and a visual acuity of 20/200 or worse were treated with vitrectomy and lamina puncture of the optic disc. Preoperative visual acuity, clinical examination results, and fluorescein angiography results were compared with postoperative results. RESULTS: Twenty patients (12 men and 8 women), an average age of 72 years, were enrolled. The mean duration of CRVO was 5.4 months; 14 eyes had nonischemic CRVO when first seen, while 6 had substantial ischemia. The mean preoperative visual acuity was in the counting fingers range, and the mean postoperative visual acuity was also in the counting fingers range. Complications included 5 eyes with iris neovascularization, of which 4 progressed to neovascular glaucoma; also, preoperative ischemia seemed to predispose to neovascular complications. CONCLUSION: Lamina puncture does not restore visual acuity in older patients with CRVO.

Aged↗

Depression symptom severity and reported treatment history in the prediction of cardiac risk in women with suspected myocardial ischemia: The NHLBI-sponsored WISE study.

BACKGROUND: Depression is associated with clinical events and premature mortality among patients with established coronary artery disease (CAD). Typically, however, studies in this area focus only on baseline symptom severity and lack any data concerning symptom duration or symptom history. OBJECTIVES: To describe and compare the relationships between 2 measures of depression-assessed in the form of depression symptom severity and reported treatment history-with atherosclerosis risk factors and major clinical events in a sample of women with suspected myocardial ischemia. DESIGN: Follow-up study of women who completed a diagnostic CAD protocol, including cardiac symptoms, coronary angiography, ischemic testing, and assessments of depression symptom severity and reported treatment history. SETTING: The Women's Ischemia Syndrome Evaluation (WISE), a National Heart, Lung, and Blood Institute (NHLBI)-sponsored multicenter study assessing cardiovascular function using state-of-the-art techniques in women referred for coronary angiography to evaluate chest pain or suspected myocardial ischemia. PARTICIPANTS: Five hundred five women (mean age, 53.4 years) enrolled in WISE and followed up for a mean of 4.9 years. MAIN OUTCOME MEASURES: Incidence of cardiac events, including myocardial infarction, stroke, and heart failure, and total mortality. RESULTS: Relative to those with no or less stable depression symptoms, women with elevated depression symptoms and a reported treatment history showed higher rates of smoking, hypertension, and poorer education and an increased incidence of death and cardiac events (multivariate-adjusted risk ratio, 3.1; 95% confidence interval, 1.5-6.3; P = .001). CONCLUSIONS: Among women with suspected myocardial ischemia, a combination of depressive symptom severity and treatment history was a strong predictor of an elevated CAD risk profile and increased risk of cardiac events compared with those without depression or with only 1 of the 2 measured depression markers. These findings reinforce the importance of assessing mental health factors in women at elevated CAD risk. Focusing only on baseline depression symptom severity may provide an incomplete picture of CAD risk.

Cause of Death↗

HCV core immunodominant region analysis using mouse monoclonal antibodies and human sera: characterization of major epitopes useful for antigen detection.

Monoclonal antibodies (MAbs) were generated by immunizing mice with a truncated recombinant protein corresponding to the immunodominant region (residues 1-120) of hepatitis C virus (HCV) nucleocapsid protein. The specific recognition by either human sera or mouse monoclonal antibodies of overlapping peptides spanning the core region 1-120 as well as the comparison with epitopes described earlier allowed the fine mapping of HCV core. Within the region 1-120, the major antigenic domain could be restricted to the first 45 amino acids. Indeed, the peptide S42G (residues 2-45) allowed the detection of an anti-HCV core response by all anticore-positive human sera examined. According to their epitope localization, three groups of mouse MABs could be evidenced that were directed against different regions of core. Group II MAbs recognized a strictly linear epitope (QDVKF, residues 20-24), whereas group I MABs were directed against a conformational epitope mainly located at the amino acid residues (QIVGG, 29-33). The epitope of group III MABs was also conformational (PRGRRQPI, residues 58-65). These three epitopes appeared close but different from the three major human epitopes RKTKRNTN, VYLLPR, and GRTWAQPGYPWPLY (residues 7-17, 34-39, and 73-86, respectively). Group II MAB 7G12A8 and group I MAB 19D9D6 were used in a sandwich ELISA for the capture and the detection, respectively, of viral core antigen in sera of patients with chronic HCV infection. After treatment of sera with triton x 100 in acidic conditions, amounts of viral antigen as low as 20 pg/ml of sera could be detected.

Animals↗

Metabolic effects of photodynamically induced apoptosis in an erythroleukemic cell line. A (31)P NMR spectroscopic study of Victoria-Blue-BO-sensitized TF-1 cells.

Victoria Blue BO (VB BO) is a new and promising photosensitizer currently being evaluated for photodynamic therapy (PDT). Its photochemical processes are mediated by oxygen radicals, but do not involve singlet oxygen. We used (31)P NMR spectroscopy of VB-BO sensitized TF-1 leukemic cells to gain further insight into the biochemical mechanisms underlying PDT-induced cell death. Sham-treatment experiments were performed to evaluate the effects of this photosensitizer in the absence of light irradiation. Significant metabolic differences were detected for TF-1 cells incubated with VB BO but not exposed to light, as compared with native cells (controls). These changes include reductions in phosphocreatine, UDP-hexose and phosphodiester levels (as percentage of total phosphate) and slightly reduced intracellular pH. Complete phosphocreatine depletion, significant acidification and concomitant inorganic-phosphate accumulation were observed for TF-1 cells irradiated after incubation with VB BO. Moreover, significant changes in phospholipid metabolites, i.e., accumulation of cytidine 5'-diphosphate choline and a decrease in phosphodiester levels, were observed for PDT-treated vs. sham-treated cells. Perturbations of phospholipid metabolism may be involved in programmed cell death, and the detection of a characteristic DNA ladder pattern by gel electrophoresis confirmed the existence of apoptosis in PDT-treated TF-1 cells.

Apoptosis↗

Effect of lipid composition on rat liver nuclear membrane fluidity.

Nuclear membrane fluidity is measured in rat liver by use of the fluorescence anisotropy of two probes: diphenylhexatriene and its cationic derivative trimethylammonium-diphenylhexatriene. It has been shown that, in 2-month-old rat liver cells, the bilayer surface is less fluid than the hydrophobic core. The fluidity was higher in 6-day-old rat liver nuclei, in which both the amount of cholesterol and the cholesterol/phospholipid ratio decreased. The influence of the single phospholipids, and in particular of phosphatidylcholine, has been studied by increasing the phosphatidylcholine with a choline base exchange reaction in isolated nuclear membranes. After this reaction, the fluorescence anisotropy of the bilayer surface increased, whereas at the hydrophobic core it decreased. Analysis of fatty acid composition shows an increase of phosphatidylcholine unsaturated fatty acids. The results show that the fluidity of nuclear membranes changes in relation to the lipid content and to the fatty acid composition. The role of nuclear membrane fluidity in cell function is discussed.

Age Factors↗

Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection.

In the present study, naive T cells were compared with in vivo generated effector and memory T cells expressing the same TCR specific for lymphocytic choriomeningitis virus. Upon restimulation in vitro, the same minimal concentrations of the full agonist peptide p33 and also of weak and partial agonist peptides were required for proliferation of naive, effector and memory T cells, indicating no difference in threshold of activation. However, activation kinetics were distinct. While effector cytotoxic T cells exhibited immediate ex vivo lytic effector function, naive and memory T cells required 12 h and more exposure to antigen to develop lytic activity. However, both effector and memory T cells contained IFN-gamma mRNA in vivo and required less than 3 h for secretion of cytokines upon restimulation in vitro. In contrast, naive T cells did not contain IFN-gamma mRNA and required more than 12 h for cytokine secretion. Our results show that memory T cells exhibit a unique phenotype in that they produce cytokines and commit to proliferation as rapidly as effector cells, whereas they resemble naive T cells in the time requirement for development of cytolytic function.

Animals↗

Malignant melanoma of the skin occurring during pregnancy.

The clinical course of melanoma of the skin diagnosed during pregnancy was compared with a control population of women with melanoma that occurred during the childbearing years, as recorded by the Connecticut Tumor Registry. The survival at three and five years for the 12 patients whose melanoma developed during pregnancy was significantly worse than for 175 nonpregnant controls (five-year survival 55% for pregnant women compared with 83% for nonpregnant women, P less than 0.05). Melanoma during pregnancy tended to occur more often on the trunk, a prognostically poor site, and at more advanced stage of disease than in nonpregnant women. However, when pregnant patients were matched to random, nonpregnant case-controls by age, anatomic site of primary lesion, and stage at diagnosis, three- and five-year survivals were not different. The number of pregnant women observed among this group of women was not substantially higher than expected, when estimated from Connecticut live birth rates: 13.3 pregnancies were expected and 12 pregnant women were actually observed. However, an unknown number of pregnancies end in abortion, making more exact estimates impossible. Melanoma occurring during pregnancy usually carries a poor prognosis, but once the disease is diagnosed, the course is not worse than expected considering stage of disease and primary site.

Adult↗

Anxiolytic-like behavior in rats is induced by the neonatal intracranial injection of apotransferrin.

To determine whether neonatal intracranial injection of apotransferrin (aTf), which increases myelin deposition, has behavioral effects in rats, 3-day-old rats were intracranially injected with 350 ng of aTf and tested at 25 and 60 days of age. An anxiolytic-like behavior was observed in aTf-treated rats, evidenced by an increase in the exploration of open arms in the plus maze test without changes in the locomotor activity. This behavioral profile persists until adulthood. Intraperitoneal injection of 0.75 mg/kg of picrotoxin, a GABA(A) receptor channel antagonist, abolished this anxiolytic-like behavior, indicating that neonatal aTf induces a long-lasting increase in GABA(A) receptor functionality.

Animals↗