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Biomedical subjects

N Dubin

Publications and source records attributed to N Dubin.

At least 37 records · Page 2Linked to original sources

The prognostic significance of nuclear DNA content in malignant epithelial tumors of the ovary.

Recent studies have indicated that the nuclear DNA content of certain malignant neoplasms can be used as an adjunct in predicting their biologic behavior. The DNA content of 99 ovarian carcinomas was determined by flow cytometric analysis of nuclei obtained from paraffin-embedded tissue. Of the 99 tumors, 51 were diploid and 48 showed one or more aneuploid peaks. The 5-year survival for patients with diploid tumors (50%) was significantly higher than for patients with aneuploid tumors (22%) (P less than 0.01). Other factors which significantly affected survival were clinical stage (P less than 0.001), tumor pattern grade (P less than 0.01), DNA index (P less than 0.01), the presence of ascites (P less than 0.001), peritoneal carcinomatosis (P less than 0.0001), and residual tumor at second-look laparotomy (P less than 0.05). Diameter of the primary ovarian tumor, diameter of the largest peritoneal implant before debulking, and the percent S-phase had no significant correlation with survival. Of 16 patients with aneuploid tumors who underwent second-look laparotomy, nine (56%) had residual tumor, compared to six of 22 of patients with diploid tumors (27%). Of seven patients with aneuploid tumors and a negative second-look laparotomy, four (57%) died from recurrent tumor. By comparison, of 16 patients with diploid tumors and a negative second-look laparotomy, only four (25%) died from recurrent tumor. The determination of DNA ploidy in ovarian carcinomas may be used as an adjunct in predicting tumor behavior, response to chemotherapy, and late recurrence of disease.

Adult↗

Simultaneous assessment of risk factors for malignant melanoma and non-melanoma skin lesions, with emphasis on sun exposure and related variables.

The purpose of this case-control study was to identify differences in risk factors between melanoma and non-melanoma skin lesions. The study group, interviewed from 1979 to 1982, consisted of 289 subjects with melanoma, 75 subjects with non-melanoma sun-related skin lesions and 527 controls. Simultaneous comparison of the three subgroups was accomplished by polychotomous logistic regression. The highest exposure category of lifetime sun exposure was associated with a nearly threefold risk of both melanoma and non-melanoma. Poor tanning was associated with an approximately twofold risk of both disease types. Similarly, northern European ethnicity was associated with an approximately twofold risk of disease. Number of moles on the body exhibited a relationship with melanoma only: having more than 25 moles, compared to their absence, was associated with a thirteenfold risk of melanoma. History of freckling was associated with a twofold risk of melanoma, but no increase in the risk of non-melanoma. Alternatively, mixed indoor-outdoor recreational exposure was associated with a 50% increased risk of non-melanoma, but a 25% decreased risk of melanoma. History of severe sunburn was associated with a twofold risk of non-melanoma only. For history of prior sun-related lesions the nearly sevenfold risk of melanoma was exceeded by the 14-fold risk of non-melanoma.

Case-Control Studies↗

Prognostic factors for malignant mixed müllerian tumors of the uterus.

This study examined factors affecting the survival of 28 consecutive patients with malignant mixed Mullerian tumors diagnosed at New York University Medical Center from 1971 through 1985. The cumulative 5-year survival for all patients was 38%. Patients with pedunculated tumors (18/25) had a significantly improved 5-year survival of 53% compared with patients having a tumor with a broad-based attachment (7/25), all of whom died within 1 year (p less than 0.01). Eleven patients whose tumors demonstrated vascular invasion had a worse prognosis compared with 14 patients without demonstrable vascular invasion (18% versus 53% 5-year survival; p less than 0.05). Interestingly, patients with pedunculated tumors persisted in having an improved survival even after correcting for vascular invasion, compared with patients having broad-based tumor attachment. Small tumor size (less than or equal to 7 cm) also proved to be a significant and independent prognostic indicator for improved survival. Advanced stage, heterologous sarcomatous elements, and deep myometrial invasion (greater than one-third invasion) tended to be associated with decreased survival, but not with statistical significance. Patient age and grade of the carcinoma element did not appear to affect survival.

Aged↗

Sex, drugs, and HIV infection in a New York City hospital outpatient population.

Persons attending outpatient clinics at Bellevue Hospital Center in Manhattan, New York City were invited to be tested for antibodies to human immunodeficiency virus (HIV). In pretest counseling, males were asked if they had injected nonprescription drugs or engaged in sex with other men since January 1, 1977; if so, they were asked not to participate and were referred elsewhere for testing. Face-to-face interviews and HIV testing were completed for 1,119 subjects with no prior indication of HIV seropositivity. Willingness to participate in the study was significantly greater among women than men and among younger than older persons. After exclusion of two subjects with indeterminate HIV serology, seroprevalence was 6.3% (70/1,117) overall, 7.1% (26/368) among men, and 5.9% (44/749) among women. HIV seropositivity among female i.v. drug users was 37% (27/74). Among heterosexuals without other HIV risk factors, estimated seroprevalences were 2.7% (25/924) overall, 3.3% (10/305) among males, and 2.4% (15/619) among females. Among heterosexual men, the data suggested associations of HIV seropositivity with sex with prostitutes and sex with numerous partners. Multiple logistic regression analysis indicated that significant predictors of HIV infection among women were a history of sexual contact with a male intravenous drug user, recent last use of intravenous drugs, and long duration of residence in New York City. Sexual intercourse with persons from AIDS risk groups was reported by 11% of men and 18% of women. The modal method of birth control reported by both men and women was "no method".

Adult↗

Biochemical changes associated with blood pressure reduction induced by calcium supplementation during pregnancy.

In a study population that comprised 34 normal black pregnant women, biochemical changes are compared between a group of women who received 1.5 gm of calcium supplementation a day and a group of women who received placebos. The blood pressure-lowering effect of calcium supplementation appears to involve a mechanism that relates parathyroid hormone and plasma renin activity. Other alterations in calcium and magnesium metabolism, as reflected by increased urinary calcium excretion and serum magnesium levels, may also contribute to this effect. Subgroups of study participants with initial (less than 26 weeks' gestation) low levels of serum calcium and plasma renin activity are the ones with the largest reductions in blood pressure. Whether these alterations can produce a reduction in the incidence of pregnancy-induced hypertension is the next question to be answered in this area.

Adolescent↗

Endometrioid and clear cell carcinoma of the ovary. Factors affecting survival.

Eighty-five patients, 52 with endometrioid carcinoma (EC), nine with mixed endometrioid and clear cell carcinoma (MC), and 24 with clear cell carcinoma (CC), were studied to determine if prognosis was affected by (a) mixed tumor histology, (b) grade of the endometrioid component in ECs, and MCs, (c) presence of benign or malignant squamous differentiation in ECs, (d) solid versus tubular histology in CCs, (e) endometriosis in the same ovary as the tumor or elsewhere in the pelvis, (f) tumor stage, (g) patient age, or (h) presence of a coexisting carcinoma of the endometrium. The 5 year survivals for the ECs, MCs, and CCs were 52%, 22%, and 69%, respectively, for all stages. The 5 year survivals for Stage I ECs and CCs were 82% and 93%, respectively. None of these differences were statistically significant. Higher stages of disease for all three tumor types and higher grades of the endometrioid component of the ECs and the MCs were associated with significantly decreased survival. Patients with CCs had a significantly increased incidence of pelvic endometriosis (67%) versus patients with ECs (17%) or MCs (22%) (p less than 0.001). Survival was not significantly affected by benign or malignant squamous differentiation in ECs, tubular differentiation in CCs, patient age, the presence of endometriosis, or a coexisting carcinoma of the endometrium.

Adenocarcinoma↗

Sun exposure and malignant melanoma among susceptible individuals.

The purpose of this case-control study was to identify susceptible subgroups, primarily based on pigmentary characteristics, at higher risk of developing melanoma when exposed to the sun. The study group, which was interviewed from 1979 to 1982, consisted of 289 consecutive patients with melanoma and 527 randomly selected controls without cancer. In general, the risk of melanoma associated with sun exposure was greater for individuals expected to be susceptible on the basis of poor ability to tan, but not other pigmentary traits. There were, in addition, some noteworthy interactions between age and sun exposure. Among subjects with poor tanning ability, the risk of melanoma associated with outdoor occupation was more than 3-fold [odds ratio (OR) = 3.3] compared to indoor occupation. In contrast, the analogous OR was much less elevated among subjects with a good ability to tan (OR = 1.5). Mixed indoor and outdoor job exposure was protective among good tanners (OR = 0.80), but not among poor tanners (OR = 1.5). A similar pattern was seen for recreational sun exposure and, when applying multiple logistic regression, for the patient's overall subjective assessment of his lifetime sun exposure. However, quantitative assessment of average hours of sun exposure did not prove to be a good indicator of melanoma risk, even among susceptible individuals. A history of severe sunburn with blistering was associated with nearly 3-fold risk among poor tanners (OR = 2.9) but was protective among good tanners (OR = 0.79). A history of nonmelanoma skin cancer or solar keratosis was a very strong risk factor (OR = 7.3), which, however, did not significantly differ in magnitude among susceptibility subgroups.

Adult↗

Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer.

Studies in animals suggest that the bispiperazinedione ICRF-187 can prevent the development of dose-related doxorubicin-induced cardiac toxicity. In a randomized trial in 92 women with advanced breast cancer, we compared treatment with fluorouracil, doxorubicin, and cyclophosphamide (FDC), given every 21 days, with the same regimen preceded by administration of ICRF-187 (FDC + ICRF-187). Patients were withdrawn from the study when cardiac toxicity developed or the cancer progressed. The mean cumulative dose of doxorubicin tolerated by patients withdrawn from study was 397.2 mg per square meter of body-surface area in the FDC group and 466.3 mg in the FDC + ICRF-187 group (no significant difference). Eleven patients on the FDC + ICRF-187 arm received cumulative doxorubicin doses above 600 mg per square meter, whereas one receiving FDC was able to remain in the study beyond this dose. Antitumor response rates were similar (FDC vs. FDC + ICRF-187, 3 vs. 4 complete responses; 17 vs. 17 partial responses; and 9.3 vs. 10.3 months to disease progression). Although myelosuppression was slightly greater in the FDC + ICRF-187 group, the incidence of fever, infections, alopecia, nausea and vomiting, or death due to toxicity did not differ between the groups. Cardiac toxicity was evaluated by clinical examination, determination of the left ventricular ejection fraction by multigated nuclear scans, and endomyocardial biopsy. In comparisons of the FDC group with the FDC + ICRF-187 group, clinical congestive heart failure was observed in 11 as compared with 2 patients; the mean decrease in the left ventricular ejection fraction was 7 vs. 1 percent when the cumulative dose of doxorubicin was 250 to 399 mg per square meter (P = 0.02), 16 vs. 1 percent at 400 to 499 mg (P = 0.001), and 16 vs. 3 percent at 500 to 599 mg (P = 0.003); and the Billingham biopsy score was 2 or more in 5 of 13 patients undergoing biopsy vs. none of 13 (P = 0.03). We conclude that ICRF-187 offers significant protection against cardiac toxicity caused by doxorubicin, without affecting the antitumor effect of doxorubicin or the incidence of noncardiac toxic reactions.

Adult↗

Breast cancer detection centers and case-control studies of the efficacy of screening.

Case-control studies of screening efficacy have been proposed as a cost- and time-efficient alternative to randomized controlled trials. Possible source populations for such retrospective studies of breast cancer screening are considered, including women from (i) pre-existing randomized trials, (ii) non-experimental population-based studies and (iii) detection centers. On practical grounds women attending detection centers are seen to comprise the most readily accessible source of adequate numbers of cases and controls. Potential biases are addressed, involving incomplete case ascertainment, self-selection, and different screening recommendations. Data from the Guttman Breast Diagnostic Institute are used for illustration.

Age Factors↗

Advanced ovarian cancer: three-year results of a 6-8 month, 2-drug cisplatin-containing regimen.

Fifty-two patients with advanced (stage III and IV) ovarian cancer were treated with a regimen of cisplatin (100 mg/m2 over 5 days) and cyclophosphamide (600 mg/m2/day 4). Treatment was repeated every 3-4 weeks for 6-8 months and followed by second look surgery. The median follow up for this single institution study (1980-1984) is 36 months. The median progression-free survival (projected) is 24 months and the median overall survival (projected) is 37 months in this group of patients with unfavorable pretreatment characteristics: median age: 61, median performance status (ECOG) 2, poorly-differentiated tumors: 60%, extensive residual tumors (greater than 2 cm): 65%. Pretreatment performance status was the only independent predictor for prolonged survival. Pathologically documented complete responses were observed in 23% of all patients and 43% of the patients who underwent second-look surgery (28 patients). Neurotoxicity from this regimen was substantial: it occurred in 65% of cases, was severe in 17% and was often not entirely reversible. The results with this intensive 2-drug cisplatin-containing regimen compare favorably to other more complex regimens in the literature. It is possible that the 'dose intensity' of cis-platinum may be the most important element of current therapeutic regimens in ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Secondary ovarian carcinoma: a clinical and pathological evaluation.

A retrospective clinical and pathological analysis was performed of 96 patients with secondary ovarian carcinoma diagnosed between January 1972 and June 1985 at New York University Medical Center. Secondary tumors accounted for 17.4% (96/553) of ovarian malignancies. The most common sites of origin were breast (32 cases), unilateral ovary (with contralateral metastases) (20), endometrium (14), colon (12), stomach (6), cervix (2), ileum (2), and 1 each for 8 additional sites. The patients ranged in age from 19 to 87 years, averaging 54.8 years, and 55 patients were postmenopausal. Ninety percent of the patients had extraovarian metastases at the time of abdominal surgery. The ovarian metastases tended to be bilateral for breast, colon and stomach, and unilateral for endometrial and ovarian primary sites. The metastases tended to be solid except for colon. The overall survival rate was 24.1% at 5 years and 7.1% at 10 years. Comparison of median survival times for the various major primary sites showed a significant overall difference (p = 0.04) and was as follows: gastric primary 0.79 years, breast 1.9 years, ovary 2.0 years, colon 3.0 years, and endometrium 3.4 years. Postmenopausal patients with unilateral ovarian carcinoma and contralateral metastases had a significantly (p = 0.04) longer median survival time (4.2 years) than analogous premenopausal patients (1.3 years). For breast and endometrium, menopausal status was not significantly associated with survival differences. These findings should prove useful in the differential diagnosis of ovarian tumors and in the medical management of these patients.

Adult↗

Risk factors for infection with human immunodeficiency virus among intravenous drug abusers in New York City.

We report here the results of a survey of 308 intravenous drug abusers recruited from hospital-based methadone maintenance or drug detoxification programmes located in Manhattan, New York City. Complete interviews and serological analyses for antibodies to human immunodeficiency virus (HIV) using both enzyme-linked immunosorbent and Western blot assays were obtained from 290 (94%) of the subjects. HIV antibodies were found by both assays in 147 (50.7%) of the tested subjects; conflicting results were found in three (1%) of the subjects; and negative results on both tests were found in 140 (48.3%) of the subjects. Logistic regression analysis identified significant relative risks for HIV infection associated with the frequency of drug injection and the proportion of injections in 'shooting galleries'. Additional risk among men was associated with a history of homosexual relations. Traditional efforts taken by subjects to clean syringes between uses, such as washing with water or alcohol, showed no evidence of being protective. Programmes aimed at prevention of HIV infection should focus on reducing use of shooting galleries and sharing of needles and syringes as well as reducing intravenous drug abuse generally.

Adult↗

Risk assessment for case-control subgroups by polychotomous logistic regression.

Case-control studies involving more than two disease and referent categories may be analyzed by means of polychotomous logistic regression, an extension of the usual dichotomous logistic regression model. Although the standard method still may be used to compare the several disease subgroups in pairs, the polychotomous approach is advantageous in that it allows simultaneous estimation of the disease-specific parameters and direct hypothesis testing involving multiple disease categories. This is especially useful for assessing whether different disease types have different risk factors. The method is applied to a large case-control study of breast cancer involving three disease categories for which both categoric and continuous risk factors are considered. Substantive epidemiologic interpretation of polychotomous regression outputs is emphasized, as well as providing illustration of the practical aspects of the statistical method.

Adult↗

Prognostic significance of squamous differentiation in stage I endometrial adenocarcinoma.

The prognostic implication of benign and malignant squamous differentiation was examined in 267 consecutive patients with stage I endometrial carcinoma. Patients with adenosquamous carcinoma had a significantly poorer ten-year survival rate (54.7%) than patients with adenocarcinoma (70.5%) or adenoacanthoma (87.4%). This was related to a tendency for adenosquamous carcinoma to be associated with poorly differentiated glandular elements and to deeply invade the myometrium. The mean depth of myometrial penetration was 57% for adenosquamous carcinoma compared with 24% for adenocarcinoma and 19% for adenoacanthoma. To examine the prognostic significance of malignant squamous differentiation independently of the grade of the associated glandular component, the subgroup of patients with well-differentiated adenocarcinoma was compared. Patients with well-differentiated adenosquamous carcinoma persisted in having a worse prognosis (58.3% ten-year survival rate), compared with adenocarcinoma (84.3% ten-year survival rate), which was explained by the propensity of adenosquamous carcinoma to deeply invade the myometrium.

Actuarial Analysis↗

Prospective evaluation of cardiotoxicity during a six-hour doxorubicin infusion regimen in women with adenocarcinoma of the breast.

In order to test the possible cardiac-sparing effect of doxorubicin administered by six-hour intravenous infusion and to prospectively evaluate the role of resting left ventricular ejection fraction in monitoring these patients, 33 women with advanced breast cancer were treated with combination chemotherapy containing 5-fluorouracil, cyclophosphamide, and doxorubicin. Doxorubicin was administered via a femoral catheter as a six-hour infusion. Cardiac function was monitored prior to therapy and at intervals during therapy by history and physical examination and by measurement of resting left ventricular ejection fraction with gated pool radionuclide angiography. Twenty-six responses were observed (complete response, seven [21 percent]; partial response, 19 [57 percent]). Systemic toxicity included alopecia, myelosuppression, and nausea and vomiting. There was a progressive fall in resting left ventricular ejection fraction during treatment from a median baseline value of 0.63. Mean fall from baseline left ventricular ejection fraction at a cumulative doxorubicin dose of 200 to 300 mg/m2 was 0.06 (p less than 0.005); at 301 to 449 mg/m2 it was 0.09 (p less than 0.0005); and at 450 mg/m2 or greater it was 0.15 (p less than 0.0005). Clinical congestive heart failure developed in three patients. Even though the decrease in left ventricular ejection fraction was often within the "normal range" (left ventricular ejection fraction 0.50 or greater), these changes were progressive and appeared to be part of a continuum of doxorubicin-induced myocardial damage. Steady-state infusion levels of doxorubicin in plasma ranged from 90 to 120 nM. They confirm the hypothesis that lower concentrations can be achieved by continuous infusion rather than by bolus infusion. In this study, however, administration of doxorubicin by six-hour infusion did not appear to have a major cardiac-sparing effect. Studies of anthracycline cardiac toxicity should include determination of baseline left ventricular ejection fraction and serial observations during therapy. Failure to include deteriorations in function above an arbitrary cutoff point or to make observations only at higher cumulative doses may underestimate drug-induced myocardial damage.

Adenocarcinoma↗

Prognosis of patients with pathologic stage II cutaneous malignant melanoma.

The prognostic relevance of the extent of nodal metastases, lesion thickness, level of invasion, site of lesion, satellitosis, age, sex, and year of diagnosis and treatment were assessed in 213 consecutive patients with pathologic Stage II malignant melanoma (157 with clinical Stage I disease and 56 with clinical Stage II disease). Of these factors, only three were significant: 1) clinical status of the lymph nodes (p less than 0.0001); 2) thickness of the primary lesion in the ranges of less than 2.0 mm, 2.0 to 4.9 mm, and 5.0 mm or greater (p = 0.002); and 3) level of invasion (p = 0.0002). The extent of nodal metastases in those patients with clinical Stage I disease was not significant. The difference in survival between patients with clinically negative/histologically positive nodes (clinical Stage I) and clinically positive/histologically positive nodes (clinical Stage II) was apparent throughout the follow-up period. The 5- and 10-year survival rates for the clinical Stage I patients were 44% and 28%, respectively, and for the clinical Stage II patients 21% and 12%, respectively (p less than 0.0001). A 5-year cumulative survival rate of 65% was achieved for clinical Stage I patients having primary lesions of less than 2.0 mm in thickness, while it was 19% for patients having primary lesions of 5.0 mm or more in thickness. For pathologic Stage II malignant melanoma patients, prognosis is most dependent on the clinical status of the lymph nodes, not on the number of lymph nodes with micrometastases.

Actuarial Analysis↗