Noninvasive investigations in vascular disease. St Mary's Fellows. ISVI (Italian Society for Vascular Investigations).
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Biomedical subjects
Publications and source records attributed to K Myers.
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PURPOSE: The detection of melanoma cells in the circulation by polymerase chain reaction (PCR) assays has been shown by several investigators to correlate with the stage of the disease and possibly with prognosis. PATIENTS AND METHODS: We performed prospective studies on 276 patients with primary melanoma and regional lymph node (LN) metastases to assess the predictive value of PCR detection of tyrosinase and melanoma antigen recognized by T cells-1 (MART-1) in the blood for recurrence of melanoma. RESULTS: PCR tests for gp 100, Muc-18, and p97 reacted with RNA in blood from healthy subjects and were considered unsuitable for patient monitoring. The tests were most frequently positive in the first 3 months after surgery. There were 47 recurrences in 123 patients who had been followed up for 18 months. Assays within 3 months of surgery predicted recurrence from melanoma in 66% of the latter (tests for tyrosinase alone detected 51% and MART-1 alone 21% of the patients). Hence, 34% of recurrences were not predicted by tests in the early postoperative period. This did not appear to be because of marker-negative melanoma because summation of tests over the first year identified 89% of those with recurrent disease. CONCLUSION: Positive tests were recorded in 35% of patients who remained disease free, but it is too early to assess whether these represent false-positive results. The false-negative results raise the question of whether the assays will provide a reliable basis for selection of patients for adjuvant therapy.
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Abdominal aortic aneurysms are more frequently diagnosed while they are asymptomatic, by ultrasound scanning or computerized tomography (CT). Large aneurysms should be treated. Open surgical repair is well proven but is a major procedure with some risk and a slow convalescence. New endoluminal techniques, inserting grafts through the femoral artery involve minimal trauma and risk, with rapid recovery, but long term success has yet to be confirmed. At present, we consider that endoluminal grafts should be reserved for patients at high risk, but with increasing experience they could be used in more than 50% of cases.
Recent developments in vascular surgery have occurred in many areas. The topics of intimal hyperplasia and reperfusion injury are the subject of much current research and possible methods of treatment are at an early stage of development. Advances in perioperative care have contributed to a reduction in mortality and morbidity. Endovascular techniques are being employed widely but the indications for their use are not yet agreed. The laboratory assessment of patients has been enhanced by the availability of duplex ultrasound scanning. The indications for carotid endarterectomy are becoming less controversial and a more aggressive approach is being taken in patients with abdominal aortic aneurysm. In patients with chronic lower limb ischaemia, long bypass grafts to the level of the ankle are being performed more frequently. The use of temporary shunts in patients with major arterial injuries appears to improve the results of treatment.
The emergence of drug-resistant cancer cells is a major obstacle to cancer treatment. Resistant cells often display a multidrug-resistant phenotype that reduces the promise of combination chemotherapy, the classic approach to the prevention of drug resistance. mdr1, a member of the ABC cassette superfamily of transporters which encodes an energy-dependent drug efflux pump, is the only gene known to confer the multidrug-resistant phenotype. Other multidrug resistance mechanisms must exist, since cell lines which have this phenotype in the absence of mdr1 overexpression have been described. We report here the application of a novel approach involving expression complementary DNA library transfer to the identification of drug-resistant genes. Using this approach we establish that mrp, a member of the ABC cassette superfamily of transporters, is capable of conferring a multidrug-resistant phenotype. This approach should be useful in the identification of other novel resistance genes.
OBJECTIVE: This project was designed to provide prospective data on the clinical presentation and longitudinal course of depression in children and adolescents. METHOD: Children and their parent(s) completed a structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School Age Children) at intake, and then yearly for 3 years. Collateral data were collected on school, social, and family functioning. RESULTS: Mean length of initial depressive episode was 35.6 weeks, SD of 26 weeks. Of the 65 depressed youths who completed the 3-year follow-up, 35 (54%) disclosed another episode of depression. Demographic, family-environment, and diagnostic variables were explored as predictors of characteristics of initial episode, recurrence of depression, and psychosocial competence at follow-up. Female gender and presence of a coexisting anxiety disorder were significantly related to severity of initial depression. Family environment was the only predictor significantly related to overall psychosocial competence over 3 years. CONCLUSIONS: The findings confirm depression in youth as a valid clinical phenomenon, with substantial risk of recurrence. Increased levels of stress in the family environment were associated with poorer overall outcomes.
I compared the production of faculty-produced publications among the U.S. schools and colleges of optometry and the Department of Veterans Affairs (VA) Optometry Service. These publication rates were viewed against the schools' rankings in National Eye Institute (NEI) funding (see Part 2), student/faculty ratios, faculty salaries, and the presence of a graduate degree program. The schools and the VA grouped into three levels of publication production with five of first rank, four of middle rank, and eight of lower rank. The five leading producers in the period 1982 through 1991 were Berkeley, Alabama, Houston, VA, and State University of New York (SUNY). Since 1982 VA optometrists have authored the largest number of articles published in the Journal of the American Optometric Association and since 1985 have been the leading group of continuing education (CE) lecturers at the Academy.
Depression is now recognized to occur in children and adolescents. However, developmental stage does appear to affect the expression, course, and pathophysiology of depressive episodes. These developmental differences restrict available treatments, and challenge our understanding of the causes and processes underlying depression across the life span.
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Using a panel of 13 hybrid cell lines, we have regionally localized 22 markers to the long arm of chromosome 6. Revised or new locations are provided for 17 of the markers, and preliminary assignments to chromosome 6 of 11 loci are confirmed. The location of NT5, previously determined by antigen expression in hybrids, has been confirmed at 6q14-q15 by using a cDNA probe. Other DNA probes include one new anonymous sequence, designated D6S130, that maps to 6q12 and 4 VNTR probes that map to the proterminal band, 6q27. Probe CRI-L1065 also maps to 6q21, CRI-994 maps to 6q21-qter, and CRI-L322 maps to 6q14-15, information that may assist the merging of physical and genetic maps.
Part 1 showed that the dominant provider of ophthalmic research funding (85%) was the National Eye Institute (NEI) and that on the average optometry faculty members had received about 3% of that funding over the years. Part 2 shows how this 3% of NEI funding has been distributed among the 16 U.S. schools in existence during the period studied and why 3% is a rational result under current conditions.
This investigation developed a hierarchical multiple regression model to assess the potential risk factors for suicidality in youths 7 to 17 years old. Variables were assessed in three domains: self-perceptions, demography and diagnosis, and home/environment. The model controlled for major depressive disorder (MDD), which has confounded previous investigations, by evaluating potential risks in a diagnostically heterogenous sample, and then evaluating these risks in a subsample with MDD. Conduct problems and depressive thinking emerged as the most powerful predictors in both samples. Hopelessness, life stress, and maternal psychopathology predicted suicidality only in the total sample. Separation anxiety protected MDD youths. These results suggest that suicidal MDD youths may comprise a distinct subgroup of depressed youths.
This study followed the course of suicidal thoughts and behaviors in youths 7 to 17 years of age who recently experienced an episode of major depression. Suicidal was expressed by 72% of the youths at some time during the study. These predominantly outpatient youths tended to be suicidal on multiple occasions, but their severity of suicidality did not increase over time. Three variables at presentation predicted later suicidality: severity of initial suicidality, anger, and age. These results suggest that milder forms of suicidality represent a feature of depression rather than characterizing a subgroup of high-risk depressed youths. The results also suggest that suicidality and anger may mark a predominantly irritable form of depression as youths mature.
The binding and elution of spleen cells from plastic dishes coated with monophosphoryl lipid A (MPL) resulted in a greater than 1,000-fold enrichment of antigen-specific suppressor T-cell (TS) activity when spleen cells from mice 18 to 24 h after exposure to a low dose of type III pneumonococcal polysaccharide (SSS-III) were used. The removal of MPL-adherent TS cells resulted in an increase in the degree of amplifier T-cell (TA) activity present in the remaining MPL-nonadherent cell fraction; however, both TS and TA activities were found in the MPL-adherent cell fraction when spleen cells from mice 4 days after immunization with an optimal dose of SSS-III were examined. These findings, as well as others, suggest that both TS and TA, once activated, acquire a cell surface receptor that enables them to bind to MPL. Because of differences in the kinetics for the activation of TS and TA during the course of the antibody response and the fact that TS, but not TA, activity appears as early as 18 to 24 h after exposure to SSS-III, it is possible to use this experimental approach to obtain cell suspensions greatly enriched in TS activity.
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