[Angiotensin II--a local growth factor].
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Angiotensin II↗
Biomedical subjects
B Rosen
Publications and source records attributed to B Rosen.
Evaluating the Israeli health care reform: strategy, challenges and lessons.
Evaluating the implementation of health care reform provides important information on its effect, as well as a factual basis for deciding upon mid-course modifications. Although researchers in various countries are addressing the impact of reform, only few governments have initiated a structured, planned evaluation to accompany reform efforts. In Israel, the 1995 National Health Insurance Law earmarked 0.1% of the health care budget for research on the law, coordinated by the National Institute for Health Policy and Health Services Research. This paper describes the evaluation strategy of the JDC-Brookdale Institute which is taking part in the research efforts. Implementation of the evaluation strategy and the challenges of evaluating a major reform of the health system are discussed. The evaluation strategy combines elements of formative and summative evaluation using a 'case study' approach which seeks to integrate in-depth understanding of the changing health system and of health care provider's organizational behavior, with a variety of outcome measures. The Israeli case provides support for the proposition that an integrated approach to evaluating health reform provides a better understanding of the subject under review and thus a better basis for making useful recommendations to policy makers. In addition, such an approach enhances the validity and credibility of the data and thus the probability of making an impact, which is a main objective of formative evaluation. Examination of the Israeli case, provides important insights about evaluation of health system reform, and may benefit researchers in other countries attempting to evaluate health care reform.
Evaluation Studies as Topic↗
Functional-anatomic correlates of object priming in humans revealed by rapid presentation event-related fMRI.
Human functional-anatomic correlates of object repetition were explored in a cohort of 20 subjects using fMRI. Subjects performed an object classification task where the target objects were either novel or repeated. Objects appeared rapidly, one every 2 s, in a randomly intermixed task design similar to traditional behavioral, event-related potential (ERP), and single-unit physiological studies. Recently developed event-related fMRI methods were used to analyze the data. Clear effects of repetition were observed. Brain areas in midlevels of the processing hierarchy, including extrastriate visual cortex extending into inferotemporal cortex and left dorsal prefrontal cortex, showed reductions in the amount of activation after repetition. By contrast, early visual areas and output motor areas were activated equally by both novel and repeated objects and did not show effects of repetition, suggesting that the observed correlates of repetition were anatomically selective. We discuss these findings in relation to previous positron emission tomography (PET) and fMRI studies of item repetition and single-unit physiological studies; we also address the broad impact that rapid event-related fMRI is likely to have on functional neuroimaging.
Adolescent↗
Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects.
The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (i.v.) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably.
Adult↗
Relationship between type of insurance and care during the early course of psychosis.
OBJECTIVE: Little is known about the relationship between insurance and care in the early course of psychosis. This study explored the insurance status of first-admission psychotic patients and the relationship between type of insurance and care received up to this admission. METHOD: Data are from the Suffolk County Mental Health Project, an epidemiologic study of first-admission psychosis. Data on insurance status (N=525) were pooled from hospital records, respondents, and significant others. Logistic regression analysis, controlling for key background variables and diagnosis, was used to study the relationship between insurance and care. RESULTS: At first admission, 233 (44%) of the patients had no insurance, 78 (15%) had Medicaid or Medicare, 203 (39%) had private insurance, eight (1.5%) were insured by the Veterans Administration, and the insurance status of three (1.5%) was unknown. Having private insurance increased the likelihood of having received previous mental health treatment (psychotherapy specifically), being admitted voluntarily, being hospitalized in a community hospital rather than a public hospital, and being hospitalized within 3 months of onset of psychosis. Having Medicaid/Medicare increased the likelihood of receiving nonantipsychotic medication before this hospitalization, admission to a community hospital rather than a public hospital, having received previous mental health treatment in general, and voluntary admission. CONCLUSIONS: During the early course of psychotic illness, many people lack any type of health insurance, and this is associated with a decreased likelihood of obtaining care before their first hospital admission.
Adult↗
Imaging the living human brain: magnetic resonance imaging and positron emission tomography.
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Brain↗
The feasibility of assessing women's perceptions of the risks and benefits of fertility drug therapy in relation to ovarian cancer risk.
OBJECTIVE: To determine the feasibility of asking women undergoing fertility treatment the maximum increased risk of ovarian cancer they would be willing to tolerate in order to take ovulation-induction drugs. DESIGN: A prospective pilot study of women attending fertility clinics over a 2-month period. SETTING: Two tertiary care fertility clinics in Toronto. PATIENT(S): Sixty-one English-speaking women were approached and 85% (n = 52) were enrolled. INTERVENTION(S): A self-administered questionnaire with fertility-specific questions. Thirty-eight women also were asked to complete standardized scales of anxiety and optimism. MAIN OUTCOME MEASURE(S): Women's report of the maximum level of lifetime risk of ovarian cancer they were willing to tolerate in order to undergo fertility treatment. RESULT(S): Seventy-nine percent were willing to accept an increased risk of ovarian cancer. Only 24% understood that treatment for ovarian cancer usually was not curative. CONCLUSION(S): A majority of patients were willing to tolerate a modest increase in their lifetime risk of ovarian cancer because of fertility treatment, most basing their estimate of acceptable risk on limited awareness of the issue.
Adult↗
Diagnosis, treatment, and six-month outcome status in first-admission psychosis.
Six-month outcome status was examined in 202 first-admission inpatients with DSM-III-R schizophrenia spectrum (N = 96), psychotic bipolar disorder (N = 64), and psychotic depression (N = 42) drawn from 10 facilities in Suffolk County, New York. Schizophrenics fared significantly worse on all outcome variables rehospitalization, which ranged from 17.7 to 23.4%. Bipolars had good psychosocial outcomes regardless of clinical outcome, while the two outcome domains were uncorrelated among schizophrenics and psychotic depressed. Schizophreniform patients had significantly better outcome than those with schizophrenia or schizoaffective disorder. Posthospital treatment was generally unrelated to outcome except that fewer rehospitalized schizophrenics received continuous treatment, and patients with psychotic depression with poorer psychosocial outcome received medication less frequently. These findings highlight the different treatment needs of these diagnostic groups, especially as regards the provision of more intensive rehabilitation for schizophrenic patients and the "poor-outcome" psychotic depressed.
Adolescent↗
Rapid sequence analysis of gene trap integrations to generate a resource of insertional mutations in mice.
Gene trapping in murine embryonic stem cells is a proven method for the simultaneous identification and mutation of genes in the mouse. Gene trap vectors are designed to detect insertions within genes through the production of a fusion mRNA transcript, making the identification of the endogenous gene possible by 5' rapid amplification of cDNA ends (RACE). Although the amplification of specific cDNAs can be achieved rapidly, cloning and screening of informative-sized cDNAs has proven to be time consuming. To eliminate the need for cloning, we have developed a method for solid-phase sequencing of 5' RACE products. More than 150 independent gene trap cell lines were analyzed, and sequence information was obtained for every line successfully amplified by RACE. With the vector used in this study, 40% of the cell lines were found to contain properly spliced gene trap events. The remaining lines were either spliced inefficiently or contained deletions of the vector. These results highlight the advantage of sequencing gene trap integrations before further characterization. This work now paves the way for large-scale gene trap screens in mice and should greatly accelerate the functional analysis of the mammalian genome.
Animals↗
Expression of the verotoxin receptor glycolipid, globotriaosylceramide, in ovarian hyperplasias.
The presence of cell surface receptor glycolipid, globotriaosylceramide (Gb3), is essential to confer susceptibility to the E. coli-derived verotoxin (VT). Our earlier studies showed that Gb3 is expressed in ovarian carcinoma cell lines. The Gb3 content of normal ovary, benign and malignant primary ovarian tumors, and their metastases have now been compared by verotoxin thin-layer chromatogram (TLC) overlay of the glycolipid tissue extracts. FITC-labeled VT1 B subunit binding to frozen tumor sections was also monitored histochemically. Low to undetectable levels of Gb3 were found in "normal" ovarian tissue. Gb3 was markedly increased in both benign and malignant tumors, suggesting that increased Gb3 may be related to proliferation, rather than malignancy per se. Mucinous tumors showed the least Gb3 elevation; serous tumors were variable, showing higher levels of Gb3 in less differentiated malignant tumors. By far the highest Gb3 content was observed for secondary ovarian metastases and tumors refractory to chemotherapy. Frozen sections of neoplastic ovarian tissue overlaid with fluorescein-conjugated VT1 B subunit show extensive binding to tumor cells, particularly in poorly differentiated samples and blood vessels adjacent to, and within, the tumor mass. Tumor foci were stained but stromal tissue was consistently negative both in primary tumors and metastases. VT staining of well-differentiated primary ovarian tumor sections was weak, corresponding to their low Gb3 content, but strong staining was observed in sections from a highly differentiated primary tumor from a patient who was unexpectedly refractory to clinical chemotherapy. These studies suggest that verotoxin/Gb3 targeting may provide the basis for new treatments for ovarian cancer.
Bacterial Toxins↗
Circulating antibodies against p53 protein in patients with ovarian carcinoma. Correlation with clinicopathologic features and survival.
BACKGROUND: Genetic alterations of the p53 tumor suppressor protein are the most frequent molecular events in human carcinogenesis. For as yet unknown reasons, mutant p53 often acts as an immunogen for autoantibody generation. These autoantibodies can be detected in the serum of cancer patients. The presence of such antibodies has been identified in a subset of patients with ovarian carcinoma, but their clinical significance has not been investigated. METHODS: Serum samples from patients with ovarian carcinoma were quantitatively analyzed for the presence of p53 autoantibodies with a time-resolved immunofluorometric procedure. Tumor p53 overexpression was assessed by immunohistochemical analysis of tissue sections. Kaplan-Meier survival curves were calculated for p53 antibody positive and negative patients, and the Cox model was used to evaluate the strength of the associations between the presence of serum p53 antibodies and cancer relapse or death, and also between the presence of such antibodies and other clinicopathologic features. RESULTS: p53 antibodies were detected in the serum of 41 of 174 patients with ovarian carcinoma (24%). Antibody levels ranged from a few hundred to 9 x 10(6) arbitrary Units/L, and fluctuated during the course of the disease. p53 antibody positive patients tended to have tumors overexpressing p53, but the association between the two parameters was not statistically significant (P = 0.13). There was also no association between the presence of p53 antibodies and clinical stage, tumor histologic type, or overall patient survival. However, these antibodies were more frequently present in patients older than 50 years (P = 0.001), in patients with moderately or poorly differentiated tumors (P = 0.001), and in patients who received chemotherapy (P = 0.015), and who suffered relapse after surgery (P = 0.018). In univariate analysis, p53 antibody positive patients were at an increased risk for relapse but not death. In multivariate analysis, the differences in disease free and overall survival between patients who were p53 antibody positive or negative were not statistically significant. CONCLUSIONS: p53 autoantibodies are found frequently in the serum of patients with ovarian carcinoma. The presence of such autoantibodies was associated with older patient age, more aggressive tumors, and reduced patient disease free survival. In multivariate analysis the prognostic value of p53 autoantibodies was not statistically significant.
Adolescent↗
Expression of opioid receptors during heart ontogeny in normotensive and hypertensive rats.
BACKGROUND: The opioidergic systems are involved in modulating nociceptive stimuli. In addition, the recent results suggest that endogenous and exogenous opioids could play a role in the modulation of blood pressure and cardiac functions. However, little is known regarding the expression and role of opioid-binding sites in the heart. The decreased sensitivity to noxious stimuli in hypertensive rats raises the possibility of different developmental pattern expression of opioid-binding sites in normotensive versus hypertensive rats. METHODS AND RESULTS: Opioid receptor expression in hearts from hypertensive and normotensive rats was studied during heart development by binding assays. From P1 until P90, the development of the heart in the two rat strains was accompanied by a gradual increase in the density of kappa-opioid receptors. Hearts from hypertensive rats expressed significantly higher levels of kappa receptors compared with those of normotensive rats. At ages older than P7, mu-opioid receptors could not be detected in hearts of both strains, whereas delta-opioid-binding sites gradually increased until reaching adult levels. Seven-day-old cardiomyocyte cultures of both rat strains expressed similar densities of delta or kappa receptors to those observed in hearts from 7-day-old neonates. The mu-binding sites were not detected in cardiomyocytes cultures. Similar to the in vivo state, cultured myocytes from hypertensive rats had significantly higher levels of kappa-binding sites (1.5 fold) compared with those of normotensive rats. The kappa sites are pertussis toxin sensitive, and the state of coupling of the receptor to G protein is similar for the two rat strains. CONCLUSION: The role of opioid-binding sites in the heart is not completely clear. Hypertensive rats are known to be less sensitive to noxious stimuli compared with normotensive rats. It is controversial whether the site if application of noxious stimuli plays an important role in the sensitivity to pain in hypertensive rats. We suggest that the opioidergic system could play a role in the modulation of blood pressure in addition to its known effect on nociception.
Animals↗
Genetic counselling and testing for susceptibility to breast, ovarian and colon cancer: where are we today?
Recent advances in our understanding of the genetic characteristics of cancer will change approaches to genetic screening and counselling. Cancer results from multiple, cumulative mutations in genes that regulate cell replication and differentiation. In familial cancer a germ-line mutation is passed on in an autosomal dominant pattern, but cancer will develop in people who inherit the defect only if other mutations also occur in susceptible somatic cells. The tumour-suppressor gene known as BRCA1 is thought to affect half of those families who have an inherited breast cancer syndrome and most families with a breast and ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in surveillance genes that protect DNA from the spontaneous errors that occur during cell division. Because there are no outcome data on which to base practice guidelines for genetic screening or management of asymptomatic carriers in families at risk, testing should be restricted to research settings.
Breast Neoplasms↗
Patients' preferences for therapy in advanced epithelial ovarian cancer: development, testing, and application of a bedside decision instrument.
The objective of this study was to determine a patient's preference for treatment in the poor prognostic situation of advanced epithelial ovarian cancer. A standardized method of information transfer was developed and pretested for feasibility, acceptability, comprehension, interobserver reliability, and validity. The Decision Board (DB) describes to the patient who has completed surgery for suboptimally debulked ovarian cancer two treatment options, their potential side effects, and possible outcomes. The psychometric properties of the DB were determined in 37 volunteers without cancer and 11 women following first-line chemotherapy for ovarian cancer. The Board was then administered to 12 patients with stage IIIc and IV ovarian cancer at the point of deciding future chemotherapy. The feasibility of presenting poor prognostic information, patient comprehension in an emotionally charged situation, and her treatment choice were determined. Observation of patient-physician interviews revealed that survival information is not usually discussed on the initial consultation. Using the DB, it was feasible to provide survival information to 98% of the healthy women. Comprehension was high, with 96% of the questions being correctly answered. Interobserver reliability was high (kappa = 1.00). The construct that hypothesized that understanding information is a determinant of choice was verified, as 95.2% of women had predictable shifts in expressed preference. The strength of preference in healthy women was statistically significantly higher for Plan B (paclitaxel-cisplatin) than for Plan A (cisplatin-cyclophosphamide) (P < 0.001). The method of presenting survival information (median survival versus percentage survival at 3.5 years) influenced choice (P < 0.04). At the point of decision making, 33% of patients with advanced ovarian cancer chose Plan A and 67% chose Plan B. All volunteers and patients stated that they wanted to be fully informed of the choices of therapy for their disease and to be involved in treatment decisions. The DB is a reliable and valid method for sharing information about advanced ovarian cancer with patients. At the point of deciding first-line chemotherapy in this poor prognostic situation, patients still value survival more highly than the quality of life during chemotherapy.
Adult↗
Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families.
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Age Factors↗
The remuneration of dentists in a special project of the Israeli Defence Forces.
The behavior of health care professionals is known to be influenced, in part, by their method of remuneration and the financial incentives they face. Describes how the Medical Corps of the Israel Defence Forces (IDF) went about choosing a reimbursement method to increase incentives for dentists and decrease waiting time for the public. Based on q questionnaire sent to all 23 dentists working in a unique IDF civilian dental clinic, and on other information which was available on the productivity and income of these dentists, a new method of remuneration was suggested and accepted, by which a combined method of fee-for-service and salary will be introduced. The base hourly pay and per crown fee were set on levels which provide for a larger compensation range and increase the incentive for improved productivity levels. This suggested method will be investigated further and re-evaluated one year after its implementation.
Attitude of Health Personnel↗
Decentralization in a sick fund: lessons from an evaluation.
In 1988, Israel's largest sick fund embarked on a process of decentralization, which consisted of the delegation of authority from central management to two regions that were chosen as demonstration sites. Aims to examine the extent to which the decentralization plan was implemented, to identify the major difficulties in implementation and to evaluate the process of implementing organizational change. Contends that the demonstration programme was implemented in part only, and that difficulties did arise during implementation. Our evaluation of the decentralization process led us to develop conceptual diagnoses of the various problems that might arise during decentralization and derive lessons for successful implementation. Evaluation taught us that when implementing a plan of decentralization, it is beneficial to make a clear division of responsibilities; develop control instruments and an information infrastructure; improve the skills of managers; appoint a team responsible for implementing decentralization, and establish a joint forum for working out problems between central management and sub-units; and clarify organizational policy on the central operational issues facing sub-units. Expresses the hope that the conclusions drawn here will help other organizations in Israel and abroad in planning and implementing decentralization.
Decision Making, Organizational↗