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Biomedical subjects

W D Dupont

Publications and source records attributed to W D Dupont.

At least 73 records · Page 4Linked to original sources
PubMed1989

Influence of exogenous estrogens, proliferative breast disease, and other variables on breast cancer risk.

The authors reevaluated 10,366 consecutive breast biopsy specimens of benign lesions performed between 1950 and 1968. Follow-up information was obtained on 3303 women with a median duration of follow-up of 17 years. This sample contained 84% of the patients originally selected for follow-up. The relative risk (RR) of developing breast cancer was 0.98 for women who took exogenous estrogens as compared to 1.8 for women who did not. Exogenous estrogens lowered the observed breast cancer risk in women with atypical hyperplasia (RR = 3.0 versus 4.5), proliferative disease without atypia (RR = 0.92 versus 1.9), and in women without proliferative disease (RR = 0.69 versus 0.91). Women who took estrogens before 1956 were at 2.3 times the risk of other estrogen users, presumably due to a dose effect. There was no significant association between breast cancer risk and birth control pills, cigarette smoking, or alcohol consumption. Exogenous estrogens are not associated with increased breast cancer risk in women with benign breast disease. A previous history of benign breast disease does not contraindicate replacement estrogen therapy.

Adult↗
PubMed1989

Converting relative risks to absolute risks: a graphical approach.

This paper presents a graphical method for converting relative risks to absolute risks. These absolute risk estimates are a function of the patient's current age, the patient's risk of developing cancer relative to some baseline population, the age specific cancer hazard in the baseline population, and the patient's competing mortal risk from all other causes. Graphs for breast cancer morbidity in women, cardiovascular mortality in men, and lung cancer morbidity in men illustrate the method. These graphs provide the probability of developing cancer in the next twenty years given the patient's current age and relative risk. They are derived under the proportional hazards model. A graph for lung cancer in men that uses a plausible exponential hazards model is also provided. The paper illustrates the importance of competing mortal hazard from other causes on absolute cancer risk. The strengths and weaknesses of this method are discussed. The graphs presented in this paper may be used as an aid in clinical decision making and in patient counselling.

Adult↗
PubMed1989

Genomic DNA analysis of the estrogen receptor gene in breast cancer.

A human estrogen receptor (ER) cDNA probe was used to examine genomic DNA extracted from 59 primary invasive breast cancers. The tumors were also studied histopathologically, and their ER status was assessed by hormone-binding assay and immunohistochemical analysis. Southern blots of genomic DNA samples digested with restriction endonucleases (BamHI, EcoRI, HindIII, PvuII, XbaI) revealed identical restriction fragments for each tumor, indicating preservation of gross ER gene integrity regardless of ER status, clinical stage, or histopathologic appearance. Digestion with PvuII identified a single, two-allele polymorphism with band(s) at 1.6 and/or 0.7 kb. The homozygous 1.6 kb pattern was present in 14 (24%) patients, the heterozygous 1.6/0.7 kb pattern in 29 (49%) patients and the homozygous 0.7 kb pattern in 16 (27%) patients. The PvuII restriction fragment length polymorphism (RFLP) within the ER gene showed no correlation with the results of the ER binding assay, the immunohistochemical analysis, clinical stage, or histopathologic appearance. A significant correlation was found between the genotypes and patient age at the time of tumor diagnosis. Tumors with the homozygous 1.6 kb and the heterozygous 1.6/0.7 kb patterns were observed in older women with mean ages of 64.6 and 64.4 years, respectively. In contrast, patients with tumors containing the homozygous 0.7 kb pattern were significantly younger, with a mean age of 50.4 years (p-value = 0.0024). The mechanism by which the homozygous 0.7 kb genotype is associated with breast cancer in the premenopausal age group is unknown.

Adult↗
PubMed1989

Early treatment with intravenous metoprolol for suspected acute myocardial infarction: a phase IV United States trial. Phase IV Metoprolol in Myocardial Infarction Study Group.

Recent randomized clinical trials have shown that total mortality and cardiovascular mortality are reduced by the early intravenous administration of beta-blockers to patients suspected of suffering from acute myocardial infarction. These trials were conducted on patients meeting strict entry criteria. In order to assess this therapy when applied to a broader range of myocardial infarction patients, we performed a Phase IV study of metoprolol in acute myocardial infarction. The study was designed to test whether early (less than 8 hours from onset of chest pain) intervention by practicing physicians with open label intravenous metoprolol for cases of suspected acute myocardial infarction achieved mortality results similar to those obtained in large randomized clinical trials. We studied 3824 patients treated by 741 physicians representing a broad spectrum of clinical practice in the United States. Seventy-two percent of the patients entered into the study had confirmed myocardial infarction (39% anterior, 39% inferior, 22% other locations) and 85% of all individuals treated tolerated the full intravenous dose of 15 mg of metoprolol. The 15 day total mortality and cardiovascular mortality rates were 4.9% and 4.5%; 90 day mortality rates were 6.9 and 5.9%. Patients with anterior infarctions had a significantly greater cumulative mortality rate than patients with other types of infarctions. Marked bradycardia (heart rate less than 45 beats per minute) in the first 8 hours post treatment occurred in 4.7% cases and hypotension (systolic blood pressure less than 90 mm Hg) occurred in 9.8% of cases. When compared with the results of the Göteborg and MIAMI trials of metoprolol, it appears that there is no appreciable increase in mortality or morbidity when metoprolol is used in the community practice of acute coronary care.

Adult↗
PubMed1989

Evaluation of a new highly purified pertussis vaccine in infants and children.

Purified acellular pertussis vaccine (12.5 micrograms of lymphocytosis promoting factor [LPF] and 12.5 micrograms of filamentous hemagglutinin [FHA]) was compared with conventional pertussis vaccine in a randomized double-blind study involving 40 children aged 4-6 y, 40 children aged 18-24 mo, and 50 infants. Increases in antibody were significantly greater among recipients of acellular vaccine than among recipients of conventional vaccine for antibodies to LPF in all age groups and for antibodies to FHA in infants and children aged 4-6 y; the increase in FHA antibody was also greater with acellular vaccine among children aged 18-24 mo but not significantly so. Compared with conventional vaccine, acellular vaccine was significantly associated with reduced frequency of leg pain and fretfulness at all ages and less frequent fever and anorexia at some ages. The reduced reaction rates and comparable or enhanced immunogenicity of the acellular vaccine make it an attractive candidate for larger field trials, particularly among infants.

Antibodies, Bacterial↗
PubMed1988

Intrinsic left ventricular contractility in normal subjects.

The influence of autonomic tone on left ventricular (LV) contractility, along with the range of normal values and the effects of exercise on contractile state, were studied in 12 normal volunteers. Serial reproducibility was examined in a subgroup of 6. LV contractility was estimated by the LV peak-systolic pressure to end-systolic volume relation (pressure-volume relation), and the ratio of peak-systolic pressure to end-systolic volume (pressure/volume ratio). The cuff blood pressure and radionuclide ventriculogram were recorded at rest, during exercise and during pharmacologic pressure-afterloading with phenylephrine, before and after vagal and beta-adrenergic "blockade." Both the pressure/volume ratio and ejection fraction increased during the stimulus of exercise (both p less than or equal to 0.008). After blockade, the pressure-volume relations were highly linear (r = 0.95 +/- 0.05 [standard deviation], n = 12), and there was no systematic difference in their slopes induced by blockade. The serial studies of pressure-volume relations showed no significant differences. The results demonstrated that vagal and sympathetic tone were not important in the support of LV contractility in normal subjects at rest, and that the pressure-volume relation and pressure/volume ratio are reproducible between studies. Also, the findings confirmed that both the pressure/volume ratio and the ejection fraction were sensitive to exercise-induced changes in contractility. This demonstration of intrinsic LV contractility in normal subjects, plus the reproducibility of the measurements, supports the feasibility of serial study of LV contractility.

Adult↗
PubMed1988

Laboratory and epidemiologic assessment of a recent influenza B outbreak.

A viral surveillance system in Nashville detected an outbreak of influenza B that occurred between January and March 1986. Paired sera from 32 individuals with culture-documented influenza B illness were tested using three serologic assays. Enzyme-linked immunosorbent assay (ELISA) using purified hemagglutinin-neuraminidase and plaque neutralization detected a seroresponse in 69% and 66% of these individuals, respectively. These assays were superior to hemagglutination inhibition, which detected a 41% seroresponse. ELISA was perferred because of cost and ease of performance. A group of 286 individuals, aged 1-65 years, was studied more extensively including serologic assessment before and after the influenza B outbreak. Historical information and viral throat cultures were obtained from those with influenza-like illness during the epidemic. An influenza B infection rate (seroresponse and/or positive culture) of 31% and illness rate (infection with flu-like symptoms during the epidemic period) of 13% was demonstrated using these methods. Pre-epidemic mean serum ELISA IgG titers were lower in those with, versus those without, evidence of subsequent influenza B illness (1,541 vs. 4,311, P = .0026). Children less than or equal to 15 years of age were infected more frequently than adults (44% vs. 28%, P = .04). Fever greater than or equal to 101 degrees F was reported more frequently with influenza B than non-B illness (43% vs. 18%, P = .03). These data are useful in preparing for future epidemiologic studies of influenza B and demonstrate the value of and need for standardization of ELISA as a serologic assay for influenza B.

Age Factors↗
PubMed1988

Histopathologic risk factors for breast cancer in women with benign breast disease.

Mammary epithelial hyperplasia indicates an increased likelihood of carcinoma development as it does in other organs. Prospective studies have demonstrated that in the premammography era about 70% of women undergoing surgical biopsy had no increased risk of cancer and have little if any hyperplastic alteration. About 25% of women have well-developed hyperplastic changes and have a risk elevation, controlled for age, of 1.5-2 times that of the general population. Less than 5% of women have atypical hyperplasia demonstrating some histologic features of carcinoma in situ, which indicates a risk elevation of 4-5 times. This is about one half the risk associated with microscopic carcinoma in situ. Therapeutic implications of these premalignant lesions rest predominantly in their indication for the heightened intensity of subsequent breast cancer surveillance and screening.

Breast↗
PubMed1988

Therapeutic donor insemination: the impact of insemination timing with the aid of a urinary luteinizing hormone immunoassay.

The records of 120 patients undergoing therapeutic donor insemination were reviewed to determine if the use of the enzyme immunoassay of urinary luteinizing hormone (LH) to plan inseminations decreased the number of cycles required to achieve conception. All inseminations were performed with fresh semen. Patients in group 1 (n = 26) utilized urinary LH testing in addition to basal body temperature (BBT) and cervical mucus examinations to time their inseminations, while inseminations in group 2 (n = 94) were timed with only BBT and cervical mucus examinations. The monthly fecundability of patients in group 1 was 0.13, whereas the monthly fecundability of patients in group 2 was 0.11. The mean number of inseminations was 1.4 and 1.6 per cycle for groups 1 and 2, respectively. There were no significant differences between groups 1 and 2 in regard to the number of cycles required to achieve conception. The use of a urinary LH immunoassay for insemination timing offers no benefit over conventional methods of timing (BBT, cervical mucus) when fresh donor semen is used.

Adult↗
PubMed1988

Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk.

A cohort study of women with ductal involvement by cells of atypical lobular hyperplasia (DIALH) revealed an incidence of 1.4% in benign biopsy specimens. When combined with diagnostic lobular unit alterations of atypical lobular hyperplasia (ALH), a consequent risk of invasive carcinoma of 6.8 times that in the general population was found. This relative risk for women with ALH and DIALH approaches the risk for lobular carcinoma in situ, whereas the risk for ALH with or without DIALH is 4.3 and the risk for ALH without DIALH is reduced to 2.7. Only definitive changes of DIALH with an insinuated characteristic population of cells between attenuated luminal cells and basement membrane should be so diagnosed. DIALH in association with lobular alterations that are borderline with regard to a diagnosis of lobular carcinoma in situ will increase the certainty that a medically meaningful increased risk for subsequent invasive cancer is indicated.

Adult↗
PubMed1988

Power calculations for matched case-control studies.

Power calculations are derived for matched case-control studies in terms of the probability po of exposure among the control patients, the correlation coefficient phi for exposure between matched case and control patients, and the odds ratio psi for exposure in case and control patients. For given Type I and Type II error probabilities alpha and beta, the odds ratio that can be detected with a given sample size is derived as well as the sample size needed to detect a specified value of the odds ratio. Graphs are presented for paired designs that show the relationship between sample size and power for alpha = .05, beta = .2, and different values of po, phi, and psi. The sample size needed for designs involving M matched control patients can be derived from these graphs by means of a simple equation. These results quantify the loss of power associated with increasing correlation between the exposure status of matched case and control patients. Sample size requirements are also greatly increased for values of po near 0 or 1. The relationship between sample size, psi, phi, and po is discussed and illustrated by examples.

Biometry↗
PubMed1987

Breast cancer risk associated with proliferative disease, age at first birth, and a family history of breast cancer.

The authors reevaluated 10,542 consecutive breast biopsies of women who presented at three Nashville hospitals. Median follow-up was 17 years for 3,398 women (84.4% of patients originally selected for follow-up). Breast cancer relative risks associated with no proliferative disease, proliferative disease without atypia, and atypical hyperplasia were 0.80, 1.4, and 4.0 times that for women from the Cancer in Connecticut data base, respectively (adjusted for age at biopsy, year of biopsy, and length of follow-up). Nulliparous women were at increased risk of breast cancer (relative risk = 1.6; 95% confidence interval (CI) = 1.1-2.2). Women who gave birth to their first child before age 21 years had a relative risk of 0.80, with higher cancer risks associated with later age at first birth. The effect of age at first birth on cancer risk followed a similar pattern within the no proliferative disease, proliferative disease without atypia, and atypical hyperplasia groups. Nulliparous women with atypical hyperplasia had a relative risk of 4.9 (95% CI = 2.7-8.9), while women with no proliferative disease who gave birth before age 21 years had a relative risk of 0.50 (95% CI = 0.19-1.3). Nulliparous women with a family history of breast cancer had a relative risk of 2.7 (95% CI = 1.4-5.2). Women with a family history who first gave birth by age 20, between ages 21 and 29, and after age 30 years had relative risks of 0.53, 2.1, and 4.0, respectively (95% CI = 0.08-3.8, 1.1-3.9, and 1.8-9.6, respectively). Breast size had no effect on cancer risk in women without proliferative disease. However, in women with proliferative disease, small, medium, and large breasts were associated with relative risks of 1.2, 1.4, and 2.1, respectively.

Adult↗
PubMed1987

Acute effects of halothane anesthesia on arterial and venous concentrations of propranolol in the dog.

The present study determined the effect of halothane on arterial and venous propranolol concentrations during a continuous intravenous infusion of propranolol. Arterial and venous concentrations of propranolol remained constant during the experiment in the group of dogs anesthetized only with pentobarbital. However, there was a rapid increase in arterial propranolol concentration from 88 +/- 10 ng/ml (mean +/- SEM) prior to halothane to 116 +/- 12 ng/ml (P less than 0.05) and 130 +/- 7 ng/ml (P less than 0.05) 60 and 120 min, respectively, after starting halothane anesthesia (2.0 MAC 1.74%). The increase in venous propranolol concentration lagged substantially behind that of the arterial concentration, so that, 60 min after starting halothane, the arterial to venous (A/V) concentration ratio increased from 1.13 +/- 0.05 to a maximum of 1.48 +/- 0.08. In contrast to the changes following halothane, no significant change in the A/V ratio occurred following fentanyl. Both halothane and fentanyl administration produced a small but significant increase in the free fraction of propranolol (P less than 0.05). The results from this study emphasize the importance of the choice of sampling sites in pharmacokinetic experiments, as well as excluding subtle pharmacokinetic changes during anesthesia before ascribing changes in drug effect to changes in sensitivity to the drug.

Anesthesia, Inhalation↗
PubMed1986

Lymphocyte-depleted Hodgkin's disease. Clinicopathologic review of 25 patients.

Clinicopathologic material from 25 patients with lymphocyte-depleted Hodgkin's disease was reviewed. The median age of the patients was 57 years. The patients had no prior diagnosis of Hodgkin's disease and were divided according to pathologic subtype of lymphocyte-depleted Hodgkin's disease: 11 diffuse fibrosis, 10 reticular, and four not otherwise specified. The clinical presentation included B symptoms of fever, weight loss, or night sweats (92 percent), subdiaphragmatic disease (88 percent), frequent marrow involvement (56 percent), and advanced-stage disease (100 percent). Four of 11 patients with diffuse fibrosis had peripheral adenopathy as compared with seven of 10 patients with the reticular subtype (p = 0.3); 10 of 11 patients with diffuse fibrosis had marrow involvement compared with two of nine patients with the reticular subtype (p = 0.006). Among patients who received chemotherapy, median survival was longer in the diffuse fibrosis subtype (nine patients, 39 months) than in the reticular subtype (10 patients, 10 months), p = 0.005. Of the 17 patients who received more than one cycle of combination chemotherapy with mechlorethiamine, vincristine, procarbazine, and prednisone, the median survival was 36 months with 11 (65 percent) complete remissions. In eight patients, disease remains in remission (12 to 127 months) with five patients surviving beyond five years. These results indicate that lymphocyte-depleted Hodgkin's disease has at least two clinicopathologic subtypes and is curable if adequate therapy can be given.

Adult↗
PubMed1986

Breast cancer risk of lobular-based hyperplasia after biopsy: "ductal" pattern lesions.

Three thousand three hundred three women were followed an average of 17 years following benign breast biopsy. These women comprise 84.4% of those originally targeted for follow-up. Risk of invasive breast cancer development was analyzed in relation to the hyperplasia classification scheme of Wellings et al (JNCI 1975; 55:231-73) that is based on terminal ductal-lobular units (ALA). Cancer risk was also assessed with respect to family history of breast cancer in first-degree relatives (FHBC), as well as atypical features of hyperplasia recognized by resemblance to carcinoma in situ of ductal type (ADH). There was a trend of increasing cancer risk with increasing degree of ALA lesion, reaching 1.9 with ALA-IV lesions having both qualitative and quantitative features of advanced atypical hyperplasia. When ADH lesions are removed from the analysis, any predictive power of ALA lesions is lost. ADH recognizes histologic lesions with a four- to fivefold increased risk of breast cancer. FHBC interacts with any hyperplastic lesion so as to approximately double the cancer risk.

Adult↗
PubMed1985

Atypical hyperplastic lesions of the female breast. A long-term follow-up study.

A total of 10,542 breast biopsy specimens obtained between 1950 and 1968 were studied. Examples of atypical "ductal" (ADH) and atypical lobular hyperplasia (ALH), defined as having only some features of carcinoma in situ (CIS), were diagnosed in 3.6% of these specimens. In the same series, CIS was diagnosed in 1.7% of biopsy specimens excluding those with invasive cancer. The subsequent risk of invasive breast carcinoma after ALH or ADH was 4-5 times that of the general population. Follow-up was 90% successful and extended 17 years after biopsy. History of breast cancer in a mother, sister, or daughter doubled the risk of subsequent invasive carcinoma development (to 8 times for ALH and 10 times for ADH). The authors conclude that among the epithelial hyperplastic lesions of the human breast, a minority may be recognized by their resemblance to CIS which have a clinically significant elevation of subsequent breast cancer risk. This risk is one-half that of CIS.

Adult↗