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Biomedical subjects

B Rosen

Publications and source records attributed to B Rosen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives.

Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P = 0.004; 95% CI 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth.

Adult↗
PubMed2001

Changes in insurance coverage and extent of care during the two years after first hospitalization for a psychotic disorder.

OBJECTIVE: This study examined changes in insurance coverage during the 24 months after first admission for a psychotic disorder and the relationship of insurance type to the extent of care. METHODS: The sample consisted of 443 persons who were enrolled in the Suffolk County (New York) Mental Health Project. Information about coverage-private insurance, Medicaid-Medicare, or no insurance-was obtained from hospital records and interviews. The insurance status groups were compared to examine differences in the percentage of days they received inpatient, outpatient, and day hospital care. RESULTS AND CONCLUSIONS: The proportion of persons with no insurance decreased from baseline to 24 months, from 42 percent to 21 percent. The proportion of persons with private insurance remained similar, 42 and 37 percent. The proportion of those with Medicaid-Medicare increased from 15 percent to 42 percent. Of those with Medicaid-Medicare at baseline (67 persons), 88 percent had such coverage 24 months later. Of those with private insurance at baseline (188 persons), 73 percent had the same coverage 24 months later. Of those with no insurance at baseline (188 persons), 35 percent had no insurance at 24 months, 54 percent had Medicaid-Medicare, and 11 percent had private insurance. Over the 24 months, the Medicaid-Medicare group had the most days of care, the private insurance group had the least inpatient care, and those with no insurance were least likely to receive outpatient care. There was a linear relationship between receiving more outpatient care and spending less time in the hospital and the day hospital.

Adolescent↗
PubMed2001

The disconnect: infertility patients' information and the role they wish to play in decision making.

OBJECTIVE: To determine the preferred role in medical decision making of women undergoing fertility treatments and to establish whether their knowledge of treatments is adequate to inform their choices. METHODS: Self-report survey of 404 women undergoing fertility treatments in 2 university hospitals and a private fertility clinic in Canada. RESULTS: The women had been in fertility treatment for 2.3 +/- 2.6 years; 67.8% reported taking fertility drugs. Most (61.7%) women wanted to share knowledge equally with their doctors about possible fertility treatments. However, about half wanted to decide alone or mostly by themselves about the acceptability of treatment risks and benefits (56%), what treatments should be selected (49.8%), and when to conclude treatments (54.3%). In addition, 55.1% of the women did not know their personal eventual chances of pregnancy with fertility treatment or thought it was 50% or greater. Over half of the women (57.2%) who had taken fertility drugs were unaware of a possible link between fertility drugs and increased ovarian cancer risk. The majority of women (61.8%) who knew of this possible association reported that they learned about it from the print media. Women who knew of the association had a poor understanding of the strength of the evidence or the ability to detect or treat ovarian cancer successfully, and 88.3% thought they could reduce cancer risk by following their doctors' advice. CONCLUSIONS: Despite these women's wishes to actively participate in fertility treatment decisions, they lacked the necessary information to do so meaningfully. Public health policymakers, professional and advocacy organizations, physicians, other healthcare providers, and women themselves must find ways to improve the general public's and patients' understanding about fertility treatment outcomes and risks.

Female↗
PubMed2000

BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer.

Ovarian cancer is a component of the autosomal-dominant hereditary breast-ovarian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in approximately 2% of the Jewish population. Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ovarian cancers attributable to founding mutations in BRCA1 and BRCA2 in the Jewish population and the familial cancer risks associated with each, we interviewed 213 Jewish women with ovarian cancer at 11 medical centers in North America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in this population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2. We obtained a detailed family history on all women we studied who had cancer and on a control population of 386 Ashkenazi Jewish women without ovarian or breast cancer. A founder mutation was present in 41.3% of the women we studied. The cumulative incidence of ovarian cancer to age 75 years was found to be 6.3% for female first-degree relatives of the patients with ovarian cancer, compared with 2.0% for the female relatives of healthy controls (relative risk 3.2; 95% CI 1.5-6.8; P=.002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4-3.0; P=.0001). Only one nonfounder mutation was identified (in this instance, in a woman of mixed ancestry), and the three founding mutations accounted for most of the observed excess risk of ovarian and breast cancer in relatives.

Adult↗
PubMed2000

Information needs and decisional preferences among women with ovarian cancer.

OBJECTIVES: Studies show that women with cancer want more information about and participation in all aspects of their healthcare including decision-making. However, most studies have been done on women with breast cancer, which often runs a lengthy course and has strong patient-advocacy groups. Little is known about the preferences of women with ovarian cancer, the fifth leading cause of cancer death in women, which often has a more rapidly fatal course. METHODS: This study of women with ovarian cancer investigates what information is most vital for women with ovarian cancer, their preferred role in decision-making, and the influence of sociodemographic, disease-related, and psychological factors. RESULTS: Questionnaires were completed by 105 women with ovarian cancer in two Canadian university hospital oncology clinics. Their mean age was 55.8 +/- 14. 9 years. Most were married, well-educated, and considered their health status to be excellent or good, even though over 60% had metastatic disease. Over 80% of these women wanted detailed information about ovarian cancer during the diagnosis, treatment, and posttreatment stages of their disease. In particular, they wanted information pertaining to the disease, treatment, and self-care issues. Approximately 60% of women preferred to share decision-making with their doctors at every stage of the illness. Psychological variables and disease severity were found to influence information needs and decisional preferences. In general, the more psychologically distressed the women, the more information they wanted about coping strategies and the more serious the illness, the more shared decision-making was desired. CONCLUSION: These results present a challenge to health care providers in more adequately meeting the individual information needs of women with ovarian cancer and involving them to the extent that they wish in the decision-making process.

Adult↗
PubMed2000

Psychological adjustment to familial genetic risk assessment: differences in two longitudinal samples.

Heritable cancer risk assessment is an increasingly common method of deriving valuable information relevant to deciding on appropriate screening regimens and preventive treatments. Assessments of heritable risk typically include familial-genetic evaluation, where analyses relate family pedigree to cancer risk, and DNA testing, where analyses indicate genetic mutations associated with cancer risk (e.g., BRCA1/BRCA2 mutations) or their absence. In this paper we report on the psychological responses of women given familial-genetic evaluations for ovarian cancer risk. The baseline and 6 to 12 follow-up assessments of an initial clinic-attending cohort of 65 women are compared with the baseline and 9 to 12 follow-up assessments of a second clinic-attending cohort of 60 women. Sizeable differences were found in the prevalence of clinically significant depression in these two physician or self-referred populations, as assessed by the Center for Epidemiological Studies Depression scale and in the mean scores. Hypotheses accounting for these differences are discussed.

Adaptation, Psychological↗
PubMed1999

Is radical trachelectomy a safe alternative to radical hysterectomy for patients with stage IA-B carcinoma of the cervix?

BACKGROUND: The prognosis associated with lymph node negative, early stage carcinoma of the cervix is excellent, with 5-year survival rates greater than 90%. Radical trachelectomy in combination with pelvic lymph node dissection (RVT + LPL) has emerged as an alternative to radical hysterectomy (RH) for these patients who desire preservation of fertility. However, there are limited data to support its efficacy and safety. METHODS: All patient information was collected prospectively and was subsequently extracted from the cervical cancer surgery database of the Division of Gynecologic Oncology at the University of Toronto. Patients treated by RVT + LPL for fertility preservation were compared with two groups of patients treated by RH. One control group was matched for age, tumor size, histology, depth of invasion, presence of capillary lymphatic space involvement, lymph node metastases, and use of adjuvant radiation. The other control group consisted of patients with tumor sizes </=2 cm, negative pelvic lymph nodes who had not received adjuvant radiation therapy. RESULTS: Thirty of 32 patients treated by RVT + LPL between March 1994 and November 1998 were matched. The only statistically significant difference in prognostic factors between the patients who underwent RVT + LPL and unmatched controls (556 patients) was the median depth of invasion in the adenocarcinomas (2. 0 mm vs. 4.0 mm, respectively; P < 0.02). The 2-year actuarial recurrence free survival was 95%, 100%, and 97% for the patients who underwent RVT + LPL, matched controls, and unmatched controls, respectively. The actuarial conception rate at 12 months was 37%. CONCLUSIONS: Acknowledging the small numbers and short follow-up, RVT + LPL appears to be similar in efficacy to RH. If longer follow-up with more patients confirms the above, this procedure will represent an acceptable alternative to RH for patients with early Stage I carcinoma of the cervix who desire preservation of fertility.

Adenocarcinoma↗
PubMed1999

Treatment of early epithelial ovarian cancer with chemotherapy and abdominopelvic radiotherapy: results of a prospective treatment protocol.

PURPOSE: To test the hypothesis that the combination of adjuvant chemotherapy and abdominopelvic radiation (APRT) improves the outcome of patients with early ovarian cancer compared to treatment with APRT alone. METHODS AND MATERIALS: Between 1991 and 1994, 93 patients with Stage I to III, optimally cytoreduced, invasive, epithelial ovarian cancer were treated with sequential chemotherapy and APRT. Treatment was assigned using a prognostic classification that was derived from previous cohorts of patients. Low-risk patients (n = 9) received APRT alone, intermediate-risk patients (n = 66) received two courses of cisplatin followed by APRT, and high-risk patients (n = 18) received 6 courses of cisplatin and cyclophosphamide followed by APRT. RESULTS: Disease recurred in 22 patients, and was confined to the pelvis or abdomen in 15. Nine patients died and the remainder were alive with disease after receiving salvage chemotherapy. The 3-year disease-free and overall survivals were 78% and 91%, respectively. The prognostic classification used to assign treatment was the only factor that predicted disease-free survival (83% and 59% at 3 years for low/intermediate- and high-risk patients, respectively; p = 0.03). There was no detectable difference in outcome between the present series and an historical control group treated with APRT alone. Treatment was well tolerated and only 2 patients (2.5%) developed serious complications. CONCLUSION: APRT is an effective adjuvant treatment for carefully selected patients with early ovarian cancer. The addition of chemotherapy as used in this study to APRT does not significantly improve outcome compared to APRT alone.

Adult↗
PubMed1999

Constitutive and conditional cadherin expression in cultured human ovarian surface epithelium: influence of family history of ovarian cancer.

Epithelial ovarian carcinomas arise in a simple mesothelium (ovarian surface epithelium, OSE) but exhibit properties of oviductal and endometrial epithelia. Thus, during malignant progression, their differentiation proceeds from simple to complex, in contrast to carcinomas in other tissues. Related changes in OSE of women with a history of familial ovarian cancer indicate that this aberrant differentiation is initiated very early in neoplastic progression. The mechanisms underlying this process are not understood. Because cadherins are known regulators of differentiation, we investigated the relationship of the cadherins E, N and P to OSE morphology, growth patterns and differentiation in cultures of normal and metaplastic OSE from women with (FH-OSE) and without (NFH-OSE) a family history of ovarian cancer and in the ovarian carcinoma lines OVCAR-3 and CaOV3. We used immunofluorescence, RT-PCR, in situ hybridization and Western blotting. Our results define N-cadherin as the constitutively expressed cadherin of normal and metaplastic OSE and indicate that P-cadherin is undetectable while E-cadherin expression is conditional and related to genotype, stage of neoplastic progression and growth pattern. The altered expression of E-cadherin in apparently normal OSE of women with hereditary ovarian cancer syndromes in conjunction with the known capacity of E-cadherin to induce epithelial characteristics implicates this adhesion molecule as a possible inducer of the aberrant Mullerian differentiation which characterizes epithelial ovarian carcinomas. Abnormal differentiation in such (pre)-neoplastic tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression.

Adult↗
PubMed1999

A longitudinal study of psychological adjustment to familial genetic risk assessment for ovarian cancer.

OBJECTIVES: To evaluate the psychological adjustment of women during initial genetic ovarian cancer risk assessment and at clinic follow-up, 6-12 months later. METHODS: Sixty-five subjects were assessed with the Centre for Epidemiological Studies Depression Scale (CESD), Spielberger's State Anxiety Inventory, and an 18-item, investigator-designed questionnaire yielding self-report on screening responses, worry about increased risk, identification of cancer-related deaths in relatives, worry about future cancer risks of daughters, alteration of future plans as a result of ovarian cancer risk, etc. RESULTS: Thirty-three percent of subjects had CESD scores above the established cutoff for depression at baseline and 38% had scores above cutoff at follow-up. Sixteen percent of subjects had state scores on the State-Trait Anxiety Inventory higher than 1 standard deviation above average (norm) at baseline, while only 6% had scores higher than 1 SD above average at follow-up. CONCLUSION: To identify factors associated with self-reported depression at follow-up, a series of demographic and self-reported variables (e.g., presence of identified problems in family, impact of genetic risk information, concern for daughter in the future) were entered in a multiple regression analysis with the CESD follow-up score as the dependent variable. Only one predictor accounted for a significant amount of variance in depression scores. Concern for daughter's risk in the future was associated with higher depression scores at follow-up (R = 0.33, P<0.02, R(2) = 11%).

Adaptation, Psychological↗
PubMed1999

Progression of myelinated retinal nerve fibers.

PURPOSE: To present a case demonstrating progression of retinal nerve fiber myelin and to suggest that myelinated retinal nerve fibers be considered among the peripapillary choristomas. METHOD: Case report. A 46-year-old woman demonstrated progression of myelinated retinal nerve fibers and associated retinal vascular anomalies. RESULTS: Myelinated retinal nerve fibers can be progressive. We confirm earlier reports of vascular anomalies associated with retinal nerve fiber myelin and show that they can also be progressive. CONCLUSIONS: The rarely progressive nature of myelinated retinal nerve fibers and the histopathologic studies published to date suggest that myelinated retinal nerve fibers represent a striking ophthalmoscopic feature resulting from ectopic oligodendrocytes; thus, the entity may be described as an oligodendrocytic choristoma.

Choristoma↗
PubMed1999

The effects of angiotensin II, endothelin-1, and protein kinase C inhibitor on DNA synthesis and intracellular calcium mobilization in vascular smooth muscle cells from young normotensive and spontaneously hypertensive rats.

Angiotensin II (Ang-II) and endothelin 1 (ET-1) are important peptides that induce a prolonged vasoconstriction and enhance proliferation of vascular smooth muscle cells (VSMC). These substances may have an important role in the development of hypertension and atherosclerosis. Our objectives were to determine whether there are inborn differences in the proliferation patterns of VSMC obtained from spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) by studying the effects of Ang-II and ET-1 on VSMC from those strains before the onset of hypertension, and to evaluate the roles of protein kinase C (PKC) and intracellular Ca2+ in the mechanism of action of ET-1 and Ang-II. VSMC from aortas of young (1- to 2-week-old) SHR and WKY rats were grown as primary cultures in plates for 48 h. The cells were incubated with Ang-II (0.1 to 1000 nmol/L) or ET-1 (0.1 to 100 nmol/L). VSMC were also incubated in the presence of various concentrations of a PKC inhibitor, chelerythrine (0.1-10 nmol/L). Thymidine incorporation into DNA was measured as an indicator of DNA synthesis. Intracellular free Ca2+ was determined by using FURA-2AM. ET-1 and Ang-II caused a marked dose-dependent enhancement of thymidine incorporation into DNA. The responses of VSMC from WKY and SHR to Ang-II and ET-1 were similar. In both strains, chelerythrine caused a dose-dependent suppression in the activity of ET-1 and Ang-II. However, VSMC from SHR incubated in the presence of ET-1 were more susceptible to the inhibitory effect of chelerythrine. Both Ang-II and ET-1 induced an increase of intracellular free Ca2+. ET-1 induced a larger increase than Ang-II (190% and 100% greater than baseline free Ca2+ levels, respectively), in spite of a lower concentration of ET-1 (ET-1 = 30 nmol/L; Ang-II = 100 nmol/L). Ang-II and ET-1 exerted a similar mitogenic effect on primary cultures of VSMC obtained from young SHR before the development of hypertension, compared with WKY. The mitogenic activity of Ang-II and ET-1 was accompanied by an increase of intracellular free Ca2+. The effect of ET-1 upon intracellular Ca2+ was stronger than that of Ang-II. VSMC cultures of SHR stimulated with ET-1 were more susceptible to PKC inhibition than those of WKY. The similarity of the effects of Ang- II and ET-1 on SHR and WKY does not exclude their role in the pathogenesis of hypertension and atherosclerosis, and further studies should be carried out to determine their role.

Alkaloids↗
PubMed1999

Patient preference for the management of mildly abnormal Papanicolaou smears.

Our objective was to investigate patient knowledge, desire for participation in medical decision making, and preference for the management of mildly abnormal Papanicolaou (Pap) smears (low-grade squamous intraepithelial lesions [LGSIL]) in the context of the continuing controversy between active (immediate colposcopy and biopsy) and surveillance (repeat Pap smears) management strategies. One hundred thirty-six women referred for a diagnostic colposcopy with a first-time mildly abnormal Pap smear result completed questionnaires before contact with either the nurse or physician. They were given the State-Trait Anxiety Inventory, the CESD Depression scale, and a knowledge about dysplasia quiz. They were then presented with the two management options and asked to state a preference, if any. They then completed the Problem Solving-Decision Making Scale, a measure of desire for involvement in medical decision making. The majority of women in this sample opted for the active management strategy. Management preference was related to anxiety, with the most anxious women more likely to choose the active management strategy. Management preference was not related to knowledge or to desire for an active role in decision making, although the more knowledgeable women also reported a desire for an active role in the decision-making process. Given the current controversy over the management of mildly abnormal Pap smears (LGSIL), as well as the fact that there is no conclusive evidence to support one strategy over another, the informed management preference of women affected by these decisions should be factored into the equation.

Adult↗
PubMed1999

An acute ischaemic event associated with the use of venlafaxine: a case report and proposed pathophysiological mechanisms.

Venlafaxine, a structurally novel antidepressant, belongs to a new generation of antidepressants--the serotonin/noradrenaline reuptake inhibitors. In clinical trials, venlafaxine was found safe and effective in most patients. However, significant changes in vital signs (hyper- and hypotension) and cardiac conduction abnormalities were observed in a few patients, notably in elderly patients. We present a case of an elderly woman with a pre-existing history of ischaemic heart disease, who was treated with venlafaxine, and developed acute myocardial ischaemia within the first week of treatment. This is the first report of a possible association between an acute cardiovascular event and venlafaxine. The association of venlafaxine treatment with ischaemic events could be explained by its unique pharmacological and haemodynamic properties.

Aged↗
PubMed1999

Gynecologists' perspectives regarding ovarian cancer.

OBJECTIVE: To document the perspectives, practices and knowledge of Canadian gynecologists regarding ovarian cancer. DESIGN: A mailed survey questionnaire was followed by a reminder card and a second mailing of the questionnaire. SETTING: A sample of all gynecologists practising in Canada. MAIN OUTCOME MEASURES: Knowledge related to ovarian cancer. Practices related to the screening and detection of ovarian cancer. Attitudes towards ovarian cancer. Perceived role in the care of women at risk of, or diagnosed with, ovarian cancer. Perceived educational needs of gynecologists regarding ovarian cancer. RESULTS: A total of 504 completed questionnaires were returned, providing a response rate of 46%. Most gynecologists indicated that they knew the basic facts about ovarian cancer and risk factors. Practices related to asymptomatic, low-risk women were found to be mostly in accord with current guidelines and the lack of evidence for the effectiveness of tests. Practices regarding women with suspected early or late-stage ovarian cancer varied, particularly with regard to referral to gynecologic oncologists. Many respondents indicated that they have an important role to play in the care of women after they have been diagnosed with ovarian cancer or referred to another specialist. Respondents also expressed interest in obtaining additional information about ovarian cancer. CONCLUSIONS: This study shows that there is a need for the development and dissemination of evidence-based guidelines regarding ovarian cancer. It also pinpoints areas where educational efforts could be directed.

Adult↗