Showing papers by "Emory University published in 1998"
TL;DR: For example, this article found a strong relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.
12,712 citations
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TL;DR: The theoretical structure, construct validity, and the social structural sources of the dimensions of social well-being are investigated in two studies as mentioned in this paper, and item and confirmatory factor analyses in both studies corroborate the theoretical model of social wellbeing.
Abstract: The proposal of five dimensions of social well-being, social integration, social contribution, social coherence, social actualization, and social acceptance, is theoretically substantiated. The theoretical structure, construct validity, and the social structural sources of the dimensions of social well-being are investigated in two studies. Item and confirmatory factor analyses in both studies corroborate the theoretical model of social well-being. The new scales correlate convergently with measures of anomie, generativity, perceived social constraints, community involvement and neighborhood quality. The new scales correlate discriminantly with measures of dysphoria, global well-being, physical health and optimism. Multivariate analyses in both studies substantiate the claim that social well-being is an achievement, facilitated by educational attainment and age. The state and direction of the study of adult functioning are discussed.
2,187 citations
TL;DR: Much of the CD8 T cell expansion seen during viral infection represents antigen-specific cells and warrants a revision of current thinking on the size of the antiviral response.
2,013 citations
TL;DR: Biopsy of sentinel nodes can predict the presence or absence of axillary-node metastases in patients with breast cancer, however, the procedure can be technically challenging, and the success rate varies according to the surgeon and the characteristics of the patient.
Abstract: Background Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings. Methods We enrolled 443 patients with breast cancer. The technique involved the injection of 4 ml of technetium-99m sulfur colloid (1 mCi [37 MBq]) into the breast around the tumor or biopsy cavity. “Hot spots” representing underlying sentinel nodes were identified with a gamma probe. Sentinel nodes subjacent to hot spots were removed. All patients underwent a complete axillary lymphadenectomy. Results The overall rate of identification of hot spots was 93 percent (in 413 of 443 patients). The pathological status of the sentinel nodes was compared with that of the remaining axillary nodes. The accuracy of the sentinel nodes with respect to the positive or negative status o...
1,923 citations
TL;DR: The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancingCD8 T cell immunity in chronically infected hosts.
Abstract: We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69hi, CD44hi, CD62Llo) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8– CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.
1,872 citations
TL;DR: It is found that, although thymic function declines with age, substantial output is maintained into late adulthood and this results indicate that the adult thymus can contribute to immune reconstitution following HAART.
Abstract: The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.
1,849 citations
TL;DR: The registration algorithm described is a robust and flexible tool that can be used to address a variety of image registration problems and can be tailored to meet different needs by optimizing tradeoffs between speed and accuracy.
Abstract: Purpose: We sought to describe and validate an automated image registration method(AIR 3.0) based on matching of voxel intensities. Method: Different cost functions, different minimization methods, and various sampling, smoothing, and editing strategies were compared. Internal consistency measures were used to place limits on registration accuracy for MRI data, and absolute accuracy was measured using a brain phantom for PET data. Results: All strategies were consistent with subvoxel accuracy for intrasubject, intramodality registration. Estimated accuracy of registration of structural MRI images was in the 75 to 150 µm range. Sparse data sampling strategies reduced registration times to minutes with only modest loss of accuracy. Conclusion: The registration algorithm described is a robust and flexible tool that can be used to address a variety of image registration problems. Registration strategies can be tailored to meet different needs by optimizing tradeoffs between speed and accuracy.
1,779 citations
1,689 citations
TL;DR: Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography.
Abstract: Background Blood transfusions prevent recurrent stroke in children with sickle cell anemia, but the value of transfusions in preventing a first stroke is unknown. We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then randomly assigned them to receive standard care or transfusions to prevent a first stroke. Methods To enter the study, children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher. The patients were randomly assigned to receive standard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration. The incidence of stroke (cerebral infarction or intracranial hemorrhage) was compared between the two groups. Results A total of 130 children (mean [±SD] age, 8.3±3.3 ye...
1,653 citations
TL;DR: It is shown that in a German family with Parkinson's disease a missense mutation in the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene causes a partial loss of the catalytic activity of this thiol protease, which could lead to aberrations in the proteolytic pathway and aggregation of proteins.
Abstract: Mutations of the α-synuclein gene1,2 have been identified in some familial forms of Parkinson's disease, and α-synuclein protein has been shown to accumulate in the brains of patients with the disease3. These findings suggest that Parkinson's disease may be caused by the abnormal aggregation of α-synuclein protein. Here we have identified in a German family with Parkinson's disease a missense mutation in the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene. We show that this mutation, Ile93Met, causes a partial loss of the catalytic activity of this thiol protease, which could lead to aberrations in the proteolytic pathway and aggregation of proteins.
1,605 citations
TL;DR: This report presents the conclusions and comprehensive recommendations of a WHO Expert Committee for the present and future uses and interpretation of anthropometry.
Abstract: Anthropometry provides the single most portable, universally applicable, inexpensive and non-invasive technique for assessing the size, proportions, and composition of the human body. It reflects both health and nutritional status and predicts performance, health, and survival. As such, it is a valuable, but currently underused, tool for guiding public health policy and clinical decisions. This report presents the conclusions and comprehensive recommendations of a WHO Expert Committee for the present and future uses and interpretation of anthropometry. In a section that sets the technical framework for the report, the significance of anthropometric indicators and indices is explained and the principles of applied biostatistics and epidemiology that underlie their various uses are discussed. Subsequent sections provide detailed guidance on the use and interpretation of anthropometric measurements in pregnant and lactating women, newborn infants, infants and children, adolescents, overweight and thin adults, and adults aged 60 years and over. With a similar format for each section, the report assesses specific applications of anthropometry in individuals and populations for purposes of screening and for targeting and evaluating interventions. Advice on data management and analysis is offered, and methods of taking particular measurements are described. Each section also includes a discussion of the extent, reliability and universal relevance of existing reference data. An extensive series of reference data recommended by the Expert Committee and not widely distributed by WHO hitherto is included in an annex.
TL;DR: Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity.
Abstract: This article reviews the burgeoning literature on the relationship of mood disorders and heart disease. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. This review of the extant literature is derived from MEDLINE searches (1966-1997) using the search terms "major depression," "psychiatry," "cardiovascular disease," and "pathophysiology." Studies investigating pathophysiological alterations related to CVD in depressed patients are reviewed. The few studies on treatment of depression in patients with CVD are also described. Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity. Recommendations for future research are proposed.
01 Jan 1998
TL;DR: Patients with mildly abnormal scans after exercise stress are at low risk for cardiac death but intermediate risk for nonfatal myocardial infarction and thus may benefit from a noninvasive strategy and may not require invasive management.
Abstract: Background—The incremental prognostic value of stress single photon emission computed tomography (SPECT) for the prediction of cardiac death as an individual end point and the implications for risk stratification are undefined. Methods and Results—We identified 5183 consecutive patients who underwent stress/rest SPECT and were followed up for the occurrence of cardiac death or myocardial infarction. Over a mean follow up of 642±226 days, 119 cardiac deaths and 158 myocardial infarctions occurred (3.0% cardiac death rate, 2.3% myocardial infarction rate). Patients with normal scans were at low risk (≤0.5%/y), and rates of both outcomes increased significantly with worsening scan abnormalities. Patients who underwent exercise stress and had mildly abnormal scans had low rates of cardiac death but higher rates of myocardial infarction (0.7%/y versus 2.6%/y; P<.05). After adjustment for prescan information, scan results provided incremental prognostic value toward the prediction of cardiac death. The identifi...
TL;DR: A substantial fraction of plasma cells can survive and continue to secrete antibody for extended periods of time in the absence of any detectable memory B cells, demonstrating a new mechanism by which humoral immunity is maintained.
TL;DR: Inadequate functional health literacy poses a major barrier to educating patients with chronic diseases, and current efforts to overcome this appear unsuccessful.
Abstract: Background: Inadequate functional health literacy is common, but its impact on patients with chronic diseases is not well described. Objective: To examine among patients with hypertension or diabetes the relationship between their functional health literacy level and their knowledge of their chronic disease and treatment. Methods: We conducted a cross-sectional survey of patients with hypertension and diabetes presenting to the general medicine clinics at 2 urban public hospitals. Literacy was measured by the Test of Functional Health Literacy in Adults. Knowledge of their illness was assessed in patients with diabetes or hypertension using 21 hypertension and 10 diabetes questions based on key elements in educational materials used in our clinics.
TL;DR: The findings summarized in this commentary confirm and elaborate the models of the direct and indirect pathways of information flow through the basal ganglia and provide a morphological framework for future studies.
TL;DR: Although nuclear localization of ataxin-1 is necessary, nuclear aggregation of atXS1 is not required to initiate pathogenesis in transgenic mice, demonstrating that nuclear localization is critical for pathogenesis.
Veterans Health Administration1, University of Southern California2, Harvard University3, University of Florida4, Southern Illinois University Carbondale5, University of California, San Diego6, Emory University7, Case Western Reserve University8, University of North Carolina at Chapel Hill9, Cornell University10, Medical College of Wisconsin11, Oregon Health & Science University12, University of Kansas13, Rush University Medical Center14, University of Arizona15, University of Wisconsin-Madison16, Children's Mercy Hospital17, North Shore-LIJ Health System18, University of Texas at Austin19
TL;DR: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures and represents the advent of a new, nonpharmacologic treatment for epilepsy.
Abstract: Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.
University of California, San Francisco1, Harvard University2, Hoffmann-La Roche3, Ohio State University4, Indiana University – Purdue University Indianapolis5, University of Alberta6, Emory University7, University of California, Los Angeles8, Lund University9, University of Alabama at Birmingham10, University of Gothenburg11
TL;DR: Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the α chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation.
Abstract: Background Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the α chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation. Methods We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation. Results Of the 126 patients given daclizumab, 28 (22 percent) had biopsy-confirmed episodes of acute rejection, as compared with 47 of the ...
TL;DR: In this study population, patients with inadequate functional health literacy had an increased risk of hospital admission and was strongest among patients who had been hospitalized in the year before study entry.
Abstract: Objective To determine the association between patient literacy and hospitalization. Design Prospective cohort study. Setting Urban public hospital. Patients A total of 979 emergency department patients who participated in the Literacy in Health Care study and had completed an intake interview and literacy testing with the Test of Functional Health Literacy in Adults were eligible for this study. Of these, 958 (97.8%) had an electronic medical record available for 1994 and 1995. Measurements and main results Hospital admissions to Grady Memorial Hospital during 1994 and 1995 were determined by the hospital information system. We used multivariate logistic regression to determine the independent association between inadequate functional health literacy and hospital admission. Patients with inadequate literacy were twice as likely as patients with adequate literacy to be hospitalized during 1994 and 1995 (31. 5% vs 14.9%, p Conclusions In this study population, patients with inadequate functional health literacy had an increased risk of hospital admission.
TL;DR: The finding that leptin activates CART/POMC neurons innervating sympathetic preganglionic neurons in the thoracic spinal cord suggests that this pathway may contribute to the increased thermogenesis and energy expenditure and decreased body weight observed following leptin administration.
TL;DR: Bcl-2, a protein that protects against apoptosis and blocks cytochrome c release, prevents superoxide production when it is overexpressed, and provides a mechanism for redox signaling that is concomitant with cy tochrome c-dependent activation of caspases.
01 Jan 1998
TL;DR: It is proposed that AC be defined as a tumor with neuroendocrine morphology, mitotic counts between 2-10 per 2 mm2 of viable tumor (10 high-power fields), or coagulative necrosis.
Abstract: Neuroendocrine tumors of the lung embrace a spectrum from low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), and high-grade categories of large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). We studied 200 neuroendocrine lung tumors to critically evaluate the Arrigoni histologic criteria for AC using statistical analysis to delimit more rigorously an intermediate survival for AC between TC and the high-grade tumors of LCNEC and SCLC. Histologic features that might predict prognosis were used for Kaplan-Meier and Cox proportional hazards survival analysis, and an optimal mitotic range for AC was calculated. The optimal mitotic range for AC was 2 to 10 mitoses per 2 mm2 of viable tumor (10 high-power fields). Based on this finding, we collapsed mitoses into three categories ( or = 11) and performed Cox multivariate analysis for all 200 neuroendocrine tumors. Mitotic counts were the only independent predictor of prognosis. Based on this analysis, we propose that AC be defined as a tumor with neuroendocrine morphology, mitotic counts between 2-10 per 2 mm2 of viable tumor (10 high-power fields), or coagulative necrosis. Using these criteria, the 200 neuroendocrine tumors were classified as 51 TC, 62 AC, 37 LCNEC, and 50 SCLC. The 5- and 10-year survival was 87% and 87% for TC, 56% and 35% for AC, 27% and 9% for LCNEC, and 9% and 5% for SCLC, respectively. After stratification for stage, survival for AC was significantly worse than for TC (p < 0.001); for LCNEC and SCLC it was significantly worse than for AC; but the survival for LCNEC was no different than that for SCLC.
TL;DR: The great majority of renal cell tumors are found incidentally, and the tumor stage is the same in the incidentally discovered cases as it is in the symptomatic cases.
TL;DR: Anti-apoptotic Bcl-2 family proteins function as gatekeepers to prevent the release of both cyt c and AIF and may also be involved in the direct binding of Apaf molecules as regulatory elements further downstream from the mitochondrial apoptotic signals.
TL;DR: Virus-specific CD8+ effector T cells are enriched in the lungs of mice with primary influenza pneumonia, though later detection of memory T cells (mCTL) in the mediastinal lymph nodes (MLN) or spleen by peptide-based staining protocols is at the limits of flow cytometric analysis.
TL;DR: Inadequate literacy was common and strongly correlated with poorer knowledge of asthma and improper MDI use, and patient reading level was the strongest predictor of asthma knowledge score in multivariate analysis.
TL;DR: BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that deubiquitinating enzymes may play a role in BRCA1 function, and may be a new tumor suppressor gene which functions in the B RCA1 growth control pathway.
Abstract: We have identified a novel protein, BAP1, which binds to the RING finger domain of the Breast/Ovarian Cancer Susceptibility Gene product, BRCA1. BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that deubiquitinating enzymes may play a role in BRCA1 function. BAP1 binds to the wild-type BRCA1-RING finger, but not to germline mutants of the BRCA1-RING finger found in breast cancer kindreds. BAP1 and BRCA1 are temporally and spatially co-expressed during murine breast development and remodeling, and show overlapping patterns of subnuclear distribution. BAP1 resides on human chromosome 3p21.3; intragenic homozygous rearrangements and deletions of BAP1 have been found in lung carcinoma cell lines. BAP1 enhances BRCA1-mediated inhibition of breast cancer cell growth and is the first nuclear-localized ubiquitin carboxy-terminal hydrolase to be identified. BAP1 may be a new tumor suppressor gene which functions in the BRCA1 growth control pathway.