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Biomedical subjects

R A Lew

Publications and source records attributed to R A Lew.

At least 127 records · Page 7Linked to original sources
PubMed1989

Estimation of prevalence on the basis of screening tests.

Estimates of disease prevalence based on screening tests can be severely biased unless adjusted for the sensitivity and specificity of the screening test. One such adjusted estimate, the maximum likelihood estimator proposed by Levy and Kass, can yield an extreme estimate of zero or one that has undesirable characteristics such as a standard error of zero. We develop here a Bayesian estimator which always falls between zero and one. Users without specialized software can use the maximum likelihood estimate for most circumstances and, in special cases, such as a zero estimate of prevalence, turn to the Bayesian estimate. Others can use software to carry out a complete Bayesian solution. We have provided a method to obtain numerical values for the Bayesian estimate for those ranges of sample size (20-100), sensitivity (0.7-0.9) and specificity (0.7-0.9) for which the use of this estimator seems most practical.

Algorithms↗
PubMed1989

Screening for melanoma/skin cancer: theoretic and practical considerations.

There is increasing national interest concerning strategies for the early detection of melanoma/skin cancer. Screening has been implemented on a national scale in an effort to decrease morbidity and mortality from this disease; however, many crucial questions about the proper methods and ultimate value of screening remain unanswered. In this review we apply the scientific principles of cancer screening to dermatology, address the theoretic and practical challenges of cancer screening in terms of melanoma/skin cancer, analyze existing data on skin cancer screening, and identify issues that require future research.

Humans↗
PubMed1989

Mechanisms of hypoxia-induced atrial natriuretic factor release from rat hearts.

Potential mechanisms of hypoxia-induced atrial natriuretic factor (ANF) release [A.J. Baertschi, J.M. Adams, and M.P. Sullivan. Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H295-H300, 1988] were investigated in Langendorff-perfused rat hearts. The ANF release was graded with stimulus intensity; 10 min of perfusion with Krebs-Henseleit solution equilibrated with 95, 20, 10, 5, and 0% oxygen led to peak ANF levels of 140 +/- 31 (SE), 202 +/- 20, 407 +/- 76, 659 +/- 119, and 516 +/- 83% of base-line ANF (159 +/- 14 pg/ml), respectively. Hypoxia-induced release of lactate dehydrogenase and creatine kinase did not correlate with ANF release; this finding, along with other experiments, rules out tissue damage as a significant factor. Phentolamine (1.3 microM) and propranolol (0.1 microM) each reduced peak hypoxia-induced (0% O2) ANF release to 333 and 310%, respectively, whereas atropine sulfate (15 microM) had no inhibitory effect. The three antagonists combined reduced the peak hypoxia-induced ANF release to the same extent (307%) as either phentolamine or propranolol alone. Earlier (24 h) catecholamine depletion of rats with 100 mg/kg 6-hydroxydopamine also significantly reduced peak hypoxia-induced ANF release to 330%. Neither the reduction of the ANF secretory responses by these interventions nor the remaining ANF response could be attributed to changes in atrial mechanics. Therefore, these studies demonstrate that alpha- and beta-adrenergic stimulation is responsible for approximately half the hypoxia-induced ANF release from the isolated heart, whereas an as yet undefined mechanism accounts for the remainder of the response.

Animals↗
PubMed1988

Measuring dementia: assessment of multiple deficit domains.

A fundamental problem in the assessment of dementia is the brief, but adequate measurement of intellectual impairment. We evaluated 82 demented patients of heterogeneous etiology with 21 neuropsychological tests. Factor analysis identified five deficit domains among the tests: verbal ability, visuospatial ability, verbal memory, orientation, and concentration. One test was selected from each domain to form a Brief Battery for Dementia (BBD), which was used to explore the relationship between deficit patterns and disease characteristics. The pattern of deficits among the five tests altered with increasing disease severity: Logical Memory (a test of verbal memory) was severely impaired in the earliest stages, while tests of verbal concept formation, perceptual organization, and orientation declined more slowly. This battery discriminated between demented and normal subjects, with a sensitivity of 91% and specificity of 97%. Disease severity appeared to be a primary determinant of degree, number, and pattern of deficits in dementing disorders and may be an important factor that modulates the apparent discriminating power of intellectual tests.

Aged↗
PubMed1988

Risk factors for the development of malignant melanoma--I: Review of case-control studies.

Data concerning risk factors for the development of cutaneous malignant melanoma (MM) were abstracted from published case-control studies. Relative risks (more appropriately "odds ratios") and 95% confidence intervals were quoted or calculated for each risk factor in each study. Those risk factors that were reported to be significant in over half of the studies include: phenotypic factors (blue eyes, blond or red hair, light complexion, freckles, sun sensitivity, and inability to tan); personal history of non-melanoma cutaneous cancer or precancer; higher socioeconomic status; increased numbers of nevocytic nevi; and bursts of sun exposure. Further study is needed on family history and personal history of MM; these were not found to be significant risk factors in over half the reviewed case-control studies. This review leaves out other undoubtedly important risk factors such as dysplastic nervus syndrome and race, which need investigation by the case-control method. Determination of risk factors allows the identification of that subset of the population most at risk for the development of MM. Given the continued increase in the incidence of MM, these data can help to focus preventive measures on the more susceptible subgroups of the population.

Humans↗
PubMed1986

Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses.

The relationship between hemophiliac immunodeficiency and exposures to factor VIII concentrate, LAV/HTLV-III retrovirus, and infection with Epstein-Barr virus and cytomegalovirus was examined. Exposure to factor VIII concentrate was significantly correlated with decreased percentages of T helper/inducer cells, decreased T helper/suppressor cell ratios, and decreased proliferative responses to plant mitogens. LAV/HTLV-III seropositivity was the primary predictor of increased percentages of HLA-DR-bearing mononuclear cells and decreased proliferative responses to pokeweed mitogen. Epstein-Barr virus and cytomegalovirus infections acted in a synergistic manner with LAV/HTLV-III to produce immunoregulatory defects. Increased percentages of T suppressor cells and decreased delayed cutaneous hypersensitivity skin test responses were observed in LAV/HTLV-III seropositive hemophiliacs infected with Epstein-Barr or cytomegalovirus. We conclude that hemophiliacs receiving commercial factor VIII concentrate experience several stepwise incremental insults to the immune system: alloantigens in factor VIII concentrate, LAV/HTLV-III infections, and herpesvirus infections.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Prognosis of clinical stage I melanoma patients with positive elective regional node dissection.

We tested 12 clinical and histologic variables to see which ones best predicted death from melanoma in 66 patients with positive elective regional node dissections (clinical stage I, pathologic stage II [CSI, PSII]). Despite the presence of lymph node metastases, not all patients had poor prognoses. Patients with tumors less than or equal to 3.5 mm and a percentage of positive nodes less than or equal to 20% had a 7-year survival rate of 66%. Within this low-risk group the subset with primary lesions on the trunk or extremities (except hands and feet) had a 7-year survival rate of 76%. This compares with poor 7-year survivals of 29% and 30% observed in other defined high-risk groups. Our results confirm and extend earlier observations concerning the prognoses of CSI, PSII melanoma patients and are relevant to any ongoing and future studies concerning elective regional node dissection (ERND) or adjuvant therapy trials in melanoma.

Actuarial Analysis↗
PubMed1985

Diet and 20-year mortality from coronary heart disease. The Ireland-Boston Diet-Heart Study.

In a prospective epidemiologic study of 1001 middle-aged men, we examined the relation between dietary information collected approximately 20 years ago and subsequent mortality from coronary heart disease. The men were initially enrolled in three cohorts: one of men born and living in Ireland, another of those born in Ireland who had emigrated to Boston, and the third of those born in the Boston area of Irish immigrants. There were no differences in mortality from coronary heart disease among the three cohorts. In within-population analyses, those who died of coronary heart disease had higher Keys (P = 0.06) and modified Hegsted (P = 0.02) dietary scores than did those who did not (a high score indicates a high intake of saturated fatty acids and cholesterol and a relatively low intake of polyunsaturated fatty acids). These associations were significant (P = 0.03 for the Keys and P = 0.04 for the modified Hegsted scores) after adjustment for other risk factors for coronary heart disease. Fiber intake (P = 0.04) and a vegetable-foods score, which rose with increased intake of fiber, vegetable protein, and starch (P = 0.02), were lower among those who died from coronary heart disease, though not significantly so after adjustment for other risk factors. A higher Keys score carried an increased risk of coronary heart disease (relative risk, 1.60), and a higher fiber intake carried a decreased risk (relative risk, 0.57). Overall, these results tend to support the hypothesis that diet is related, albeit weakly, to the development of coronary heart disease.

Adult↗
PubMed1985

Adjuvant therapy of cutaneous malignant melanoma: a critical review.

The emergence of revised definitions for the high-risk patient with cutaneous malignant melanoma prompts us to re-examine the current status of adjuvant therapy in this disease. We wish to address the question, "once a cutaneous melanoma is surgically removed and the patient is currently free of disease but at high risk for metastases, what can be done to prevent recurrence"?

BCG Vaccine↗
PubMed1985

Malignant melanoma prognostic factors 7: elective lymph node dissection.

Every prospective study published to date, whether randomized or nonrandomized, shows that the survival rate for patients with clinical stage I melanoma is the same, irrespective of whether they have an elective lymph node dissection (ELND). All the studies that purport to show a survival benefit from ELND have been based on retrospective data and are therefore subject to selection bias. Nevertheless, the data support the notion that there may be a small, select group of melanoma patients whose lives can be saved by ELND. This subgroup is made up of those patients who have epithelioid in small nests (ESN) melanomas. In the early stages of its evolution, this type of malignant melanoma metastasizes to regional lymph nodes and often does not have coexistent distant metastases. Other types of melanomas, when they metastasize, either bypass the lymph nodes or metastasize to the lymph node and simultaneously send distant metastases elsewhere, nullifying the anticipated benefit from an ELND. We encourage dermatologists, when they have a choice, to be supportive of those surgeons who have a choice, to be supportive of those surgeons who are actively participating in ongoing randomized trials designed to select patients who might benefit from ELND.

Analysis of Variance↗
PubMed1985

Epidemiology of cutaneous melanoma.

Although intermittent intense solar exposure and genetic traits such as fair skin continue to be associated with the risk of developing cutaneous melanoma, these factors fail to account for much of the incidence. Suggestive evidence has increased speculation that viral agents, radiation, hormones, chemicals in the workplace, and dietary factors play some etiologic role.

Diet↗
PubMed1985

Influence of estrogen administration on tumor characteristics and survival in women with cutaneous melanoma.

A prospective study on 289 women with clinical stage I cutaneous melanoma was done to determine the relationship between estrogen administration, tumor characteristics, and survival. Eighty-two women took oral contraceptives (OC) and 44 took menopausal estrogens (MPE) prior to the diagnosis of melanoma. Users of OC presented with thinner primary tumors than nonusers of OC (P less than .01). A similar trend was observed in users of MPE. Women who used OC in the year prior to the diagnosis of melanoma had statistically thinner tumors than those who had discontinued use of OC more than 1 year prior to diagnosis (P less than .025). A statistically significant preponderance of truncal lesions was observed among users of OC (P less than .01). Other tumor characteristics were unaltered by estrogen administration. Duration of use and time in relation to diagnosis of melanoma did not affect survival. Women who took hormones had slightly better 5- and 9-year survival rates than nonusers. These results suggest that prior estrogen use and, particularly, use of OC in women developing melanoma have no deleterious effect.

Actuarial Analysis↗
PubMed1985

Strategies for validation.

The easy-to-use statistical package has imposed a new hardship on the clinical researcher: too much complicated analysis. The problem is most acute in the interpretation of multivariate results that select a combination of several factors that "best" predict or explain medical outcomes. For example, these methods give rise to formulas that 1) weigh together the risk factors of smoking, blood pressure, and lipid levels as determinants of heart disease, or 2) construct from pathologic and clinical evidence a prognostic profile for disease-free rectal cancer patients. To help the clinician apply these methods, we propose that, on request, statistical packages also produce two sets of calculations that validate the primary analysis: 1) a set of simple tabulations that show how the factors and outcomes used in the primary analysis relate to one another, and 2) the results of alternative analyses that show factors which every analysis selects, factors which only appear in the primary analysis, and those which tend to substitute for one another.

Arsenic↗
PubMed1984

Cigarette smoking and malignant melanoma. Prognostic implications.

Heavy cigarette smoking (current smoking with greater than 15-pack-year smoking history), along with 13 other variables, were tested for their ability to predict death in 196 patients with clinical Stage I melanoma. A stepwise proportional hazards general linear model (Cox multivariate analysis) showed that although heavy cigarette smoking as a single variable is an adverse prognostic marker (P = 0.0065), it has only suggestive prognostic significance once thickness factors are taken into account (P = 0.0747). People who stopped smoking had the same survival as nonsmokers. Clinical Stage I patients with melanoma who were heavy smokers presented with thicker lesions than their nonsmoking counterparts (P = 0.037). Although cigarette smoking may play a role in the biologic behavior of melanoma by mediating an effect on thickness, it need not be considered as an independent stratification criterion when analyzing results of melanoma prognosis or treatment.

Adult↗
PubMed1984

"Microscopic satellites" are more highly associated with regional lymph node metastases than is primary melanoma thickness.

A multivariate analysis was performed on 20 clinical and histologic variables from 327 Stage I prospectively studied melanoma patients who underwent elective regional lymph node dissection (ERLD). Primary tumor thickness, microscopic satellites, and the elapsed interval between diagnosis and ERLD, were selected as the combination of variables that were most highly associated with clinically occult regional lymph node metastases (P = 10(-15), model chi-square). Microscopic satellites were defined as tumor nests, greater than 0.05 mm in diameter, in the reticular dermis, panniculus, or vessels beneath the principal invasive tumor mass but separated from it by normal tissue on the section in which the Breslow measurement was taken. The probability of finding nodal metastases for melanomas less than 0.75 mm thick was 0% (0/41 patients); for those 0.76-1.50 mm, 4% (4/108); 1.51-3.0 mm, 14% (14/102); and greater than 3.0 mm, 39.5% (30/76). Primary melanomas greater than 1.50 mm thick with microscopic satellites were more often associated with nodal metastases than those of similar thickness without satellites (30/57 (53%) versus 14/121 (12%), P = 0.01). Some satellites probably represent intraspecimen metastases, while others do not. Any predictive model for occult regional lymph node metastases based on data from ERLD done less than 50 days after diagnosis may underestimate the prevalence of metastases.

Adult↗
PubMed1984

Malignant melanoma prognostic factors 5: clinical staging.

Regional lymph node enlargement, as determined by palpation, is a useful prognostic factor--even if these nodes are histologically free of metastases. This is true not only for malignant melanoma but also for mycosis fungoides and carcinoma of the vulva.

Analysis of Variance↗
PubMed1984

A multivariate analysis of factors affecting wound-healing time.

For post-Mohs surgical defects of the head and neck, the width of the defect is the best predictor of the length of that time it will take the wound to heal. This conclusion is based on a multivariate analysis, testing the effect of the following factors on wound-healing time: (1) age, (2) sex, (3) sound location, (4) wound width, (5) wound length, and (6) wound length X wound width. After accounting for wound width, none of the other factors significantly influenced the rate of wound healing. The 64 wounds evaluated were dressed daily with one of five bandages. When compared with the controls, and after correcting for wound width, each of the test bandages shortened wound-healing time. Among the treatment groups, no significant differences were found in the cultures or in the appearance of the wounds.

Aged↗