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Biomedical subjects

E Anderson

Publications and source records attributed to E Anderson.

At least 55 records · Page 3Linked to original sources

Meta-analysis of medical self-help groups.

Self-help groups (SHGs) may rival all other forms of treatment sometime within the next century (see Goodman & Jacobs article in "The Handbook of Group Psychotherapy," Wiley, 1994), though the "purist" model of SHGs seems inaccurate because many professionals are actually involved. Although traditional forms of group treatment have kept pace with empirical research (Fuhriman & Burlingame, "The Handbook of Group Psychotherapy," 1994), SHGs have not. In particular, medical SHGs, often promoted by hospitals as viable treatment alternatives, have no systemized database from which to draw conclusions about overall effectiveness compared to traditional group therapies. A preliminary assessment of this area is presented using a meta-analysis of articles culled from a comprehensive review of the literature from 1970 to 1997. Results indicate that although the posttreatment analysis produced no significant differences between active and control conditions, pre to posttreatment scores indicated that SHGs produced higher patient improvement when compared to the control condition. Future implications for research and use of medical SHGs are explored.

Adult↗

I.v. regional diamorphine for analgesia after foot surgery.

Opioids administered to peripheral tissues can have significant analgesic effects in doses which would not be effective centrally. We have assessed the effects of regional diamorphine 2.5 mg i.v. in 14 patients undergoing surgical correction of bilateral arthritic foot deformities in a prospective, randomized, double-blind study. Patients acted as their own controls as only one foot received the active drug. Visual analogue scale (VAS) pain scores and wound tenderness were measured over 72 h. Diamorphine did not improve median VAS area under the curve pain scores during the first 6 h after surgery (33 (95% confidence intervals (CI) 25-46) vs 24 (17-35)). It also did not effect wound hypersensitivity when tested at 72 h after surgery (95 (47-125) vs 90 (50-125) g). There were no significant adverse effects.

Adolescent↗

Abnormal regulation of the oestrogen receptor in benign breast lesions.

BACKGROUND: In normal breast tissue the oestrogen receptor (ER) and the proliferation associated antigen Ki67 are negatively associated, indicating that ER+ cells are non-dividing, or that the receptor is downregulated as cells enter cycle. This relation is completely or partially lost in many ER+ breast cancers and in in situ proliferations associated with an increased cancer risk, where coexpression of the two markers is often found. AIMS: To determine whether similar changes can be identified in other risk associated breast lesions. PATIENTS/METHODS: Paraffin wax blocks from 12 cases of lactational change, 21 apocrine metaplasias, 22 duct ectasias, 20 sclerosing adenosis, 20 fibroadenomas, 19 phyllodes tumours, 20 radial scars, 21 papillomas (15 solitary and six multiple), 15 gynaecomastias, and nine postmortem male breast tissues were retrieved. Immunohistochemistry was used to determine the expression of ER and dual labelling immunofluorescence was used to detect cells expressing both ER and Ki67. RESULTS: Increased numbers of ER+ cells were seen in sclerosing adenosis, radial scars, papillomas, fibroadenomas, and phyllodes tumours but not in apocrine cysts (where no ER+ cells were detected) or duct ectasia (where normal numbers were found). As in the normal breast, the proportion of ER+ cells increased with age in all lesions with the exception of fibroadenomas. Coexpression of ER and Ki67 was found in an increased proportion of cells of all risk associated lesions studied. ER+ cells were less likely to be dividing than ER- cells in all cases, although this was significant only for sclerosing adenosis. The data on sclerosing adenosis, radial scars, papillomas, and fibroadenomas are comparable with those reported previously in hyperplasia of usual type, whereas those in duct ectasia are similar to those of the normal breast. The findings in all lesions, however, differed from those in ductal carcinoma in situ, where proportions of ER+ and ER+/Ki67+ cells are higher and the relation between ER+ cell numbers and age is lost. Thus, the nature and degree of dysregulation of ER in benign breast lesions is broadly in accordance with the degree of risk of developing breast cancer with which they are associated. In gynaecomastia, the proportions of ER+ and ER+/Ki67+ cells were comparable with those seen in benign female breast lesions, but changes with age were not observed. However, the changes in gynaecomastia were similar to those seen in normal male breast. CONCLUSION: These findings are in keeping with the contention that the dissociation of ER and Ki67 expression is a very early change in the pathway to many breast cancers. However, this change might only have preneoplastic importance in the hormonal milieu of the female breast.

Adult↗

The role of gender in MPH graduates' salaries.

Several studies have demonstrated that workforce roles and salaries differ substantially between men and women in administrative positions within the health care industry. Recent studies of graduates with masters of business administration (MBA) and masters of health administration (MHA) degrees have indicated that women tend to experience lower salaries, given like responsibilities. However, the impact of gender on salary has been less studied among masters of public health (MPH) graduates in the health care field. Our objective was to assess the impact of gender on salary among MPH degree graduates. Using a cross-sectional survey of all graduates from the MPH program at Yale University between 1991-1997 (n = 201, response rate = 51%), we ascertained graduates' reported salary in the first job post-graduation and reported salary in their current position. Bivariate and multivariate analyses were used to assess the unadjusted and adjusted associations between gender and salary. Salaries in both the first job post-graduation and in the current job differed significantly by gender, with women earning less than men (p-values < .05). Moreover, these differences persisted after controlling for a set of human capital measures including pre-MPH work experience, age at graduation, years since graduation, area of specialization within the MPH degree, and type of work site (governmental or nonprofit versus for-profit). Unlike studies of MBA and MHA graduates, however, this study did not find evidence that the gender-related salary gap widened as the years since graduation increased, although the sample size did not allow comprehensive testing of this trend.

Adult↗

Violent injuries among women in an urban area.

The national statistics are familiar by now: each year, more than 2 million women are raped and/or physically assaulted; more than one-third of them are injured during their most recent assault. Annually, more than 500,000 women seek medical services as a result of violence-related injuries, often from hospital emergency departments. But national statistics cannot fully capture the extent of violence experienced by women in inner-city areas, nor do they point to modifiable risk factors at a community level. This Issue Brief highlights a new study that investigates the circumstances and correlates of violent injuries among women in one urban, low-income community.

Emergency Medical Services↗

Violent injuries among women in an urban area.

BACKGROUND: Although the rate of death from injuries due to violent acts is much higher among black women than among white women in the United States, little is known about the nature and correlates of violent injuries among black women living in urban areas. METHODS: In this case-control study conducted at three emergency departments in one inner-city community (in west Philadelphia), we studied 405 adolescent girls and women who had been intentionally injured and 520 adolescent girls and women (control subjects) who had health problems not related to violent injury. Data were collected by conducting standardized interviews with use of questionnaires and by screening urine for illicit drugs. Individual logistic-regression models were constructed to identify factors associated with violent injuries inflicted by partners and those inflicted by persons other than the partners of the victims. RESULTS: The male partners of the injured women were much more likely than the male partners of control subjects to use cocaine (odds ratio, 4.4; 95 percent confidence interval, 2.3 to 8.4) and to have been arrested in the past (odds ratio, 3.1; 95 percent confidence interval, 1.8 to 5.2). Fifty-three percent of violent injuries to the women had been perpetrated by persons other than their partners. Women's use of illicit drugs and alcohol abuse were factors associated with both violence on the part of partners and violence on the part of other persons. Neighborhood characteristics, including low median income, a high rate of change of residence, and poor education, were independently associated with the risk of violent injuries among women. CONCLUSIONS: Women in this urban, low-income community face violence from both partners and other persons. Substance abuse, particularly cocaine use, is a significant correlate of violent injuries. Standard Census data may help identify neighborhoods where women are at high risk for such violence and that would benefit from community-level interventions.

Adolescent↗

Naked DNA vaccination of Atlantic salmon Salmo salar against IHNV.

A naked plasmid DNA encoding the glycoprotein (pCMV4-G) of a 1976 isolate of infectious hematopoietic necrosis virus (IHNV) obtained from steelhead Oncorhynchus mykiss was used to vaccinate Atlantic salmon Salmo salar against IHNV. Eight weeks post-vaccination the fish were challenged with a strain of IHNV originally isolated from farmed Atlantic salmon undergoing an epizootic. Fish injected with the glycoprotein-encoding plasmid were significantly (p < 0.05) protected against IHNV by both immersion and cohabitation challenge. Survivors of the first challenges were pooled and re-challenged by immersion 12 wk after the initial challenge. Significant (p < 0.05) protection was observed in all of the previously challenged groups including those receiving the complete vaccine. Fish injected with the glycoprotein-encoding plasmid produced low levels of virus-neutralizing antibodies prior to the first challenge. Neutralizing antibodies increased in all groups after exposure to the IHNV. Passive transfer of pooled sera from pCMV4-G vaccinates and IHN survivors provided relative survivals of 40 to 100% compared to fish injected with sera collected from fish immunized with control vaccines or left unhandled. In this study, DNA vaccination effectively protected Atlantic salmon smolts against challenges with IHNV.

Animals↗

Loss of STAT1 expression confers resistance to IFN-gamma-induced apoptosis in ME180 cells.

Interferon gamma (IFN-gamma) induces apoptosis in many tumor cell lines and sensitizes tumor cells to apoptosis by tumor necrosis factor family members. IFN-gamma induces the expression of many early response genes such as interferon regulatory factor-1 (IRF-1) by activation of signal transducer and activator of transcription (STAT) factor proteins. We found that ME180 cells became resistant to IFN-gamma-induced cell death after 4-5 passages in culture. These resistant cells were characterized by a loss of STAT1 expression and a loss of inducible IRF-1 expression. We describe for the first time the emergence of a STAT1-deficient ME180 cell line.

Apoptosis↗

Epithelial stem cells in the mammary gland: casting light into dark corners.

The epithelial structures of the human breast or the mouse mammary gland are derived from a relatively small number of multipotent, tissue-specific stem cells, of which we are surprisingly ignorant. We do not know how many are required to produce a complete mammary gland, how many times they divide during the process, where they are situated in the gland, or even what they look like. We want to know the answers to these questions, not just to satisfy intellectual curiosity, but also because the answers may shed light on the evolution of breast cancer. Now, studies carried out by Kordon and Smith at the National Cancer Institute have pointed the way toward a new understanding of mammary stem cells and their progeny.

Animals↗

Characterization of the dimer interface of transcription factor NFkappaB p50 homodimer.

Dimers of the Rel/NFkappaB transcription factor family form with differential stabilities through the combinatorial association of five polypeptides: p50, p52, p65, cRel, and RelB. Here, we have characterized the nature of the monomer-dimer equilibrium of the p50 homodimer. Sedimentation equilibrium studies show that the equilibrium constant for p50 dimer dissociation is in the low micromolar range. Using the X-ray crystal structure of the p50 homodimer as a guide, we have created site-directed alanine mutations at ten dimer-forming residues in p50 and measured their effects on p50 homodimerization. Characterization of these alanine mutants by a series of chemical crosslinking, size-exclusion chromatography, and sedimentation equilibrium experiments shows that the most critical residue in stabilizing the p50 dimer interface is Y267. Sedimentation equilibrium experiments show that an alanine substitution at position 267 destabilizes the dimer interface by 2.0 kcal/mol. Alanine substitutions at two other positions, L269 and V310, significantly destabilize the p50 dimer interface. These two residues are observed to mediate critical interactions in the crystal structure. Together, these three residues constitute the "hot-spot" of protein-protein interaction in p50 dimerization. Of the four charged residues in the dimer interface, R252, D254, E265, and D302, only D302 contributes significantly to p50 dimer stability. D254 appears to slightly destabilize the subunit interface. Although residues H304, R305, and F307 occupy positions at the hydrophobic core of the interface and appear to be involved in multiple interactions in the X-ray crystal structure, alanine substitutions at these positions do not significantly reduce the affinity for p50 dimerization. Upon evaluating the roles of these amino acid residues at the p50 dimer interface, we propose that differential contributions of a few key residues dictate the selectivity of dimer formation within the Rel/NFkappaB family.

Amino Acid Sequence↗

Estrogen receptor-positive proliferating cells in the normal and precancerous breast.

Recently it has been shown that epithelial cell expression of the estrogen receptor (ER) and that of the proliferation-associated marker Ki-67 are almost mutually exclusive in the normal premenopausal human breast but that coexpression frequently occurs in estrogen receptor-positive (ER+) breast cancers. This coexpression may indicate disordered expression of ER in the cell cycle or failure to suppress division of ER+ cells and could be important in neoplastic transformation. The purpose of this study was to determine whether in situ proliferations known to be associated with different levels of risk for developing breast cancer contain these coexpressing cells and, if so, the stage at which they occur. We found that ER+ proliferating cells were rare in premenopausal lobules but increased with age in the normal breast. There was no difference in nonlesional tissue between cancerous and noncancerous breasts. The percentage of dual-expressing cells was significantly increased, however, in all of the in situ proliferations and correlated positively with the level of risk of developing breast cancer. We suggest that development of at least some human breast cancers is associated with increasing failure to down-regulate ER as cells enter the cycle or to suppress division of ER+ cells. The mechanism may involve the loss of a tumor suppressor gene.

Breast↗

Results of implementation of a contemporary model for ambulance diversions in an integrated healthcare delivery system.

This brief report contains a description of a contemporary, coordinated new system for ambulance diversions, which was implemented in Edmonton area's Capital Health Region in January 1999. The development of this new system was precipitated by the combination of increasing pressures within the acute care system especially being felt within our emergency departments, and mounting evidence that the existing system for ambulance diversions was ineffectual in providing temporary relief of these pressures. The nature of the previous and the new system are compared and contrasted, and data are included to demonstrate that the new system has led to marked reductions in the number of ambulance diversions experienced regionally.

Alberta↗

Sustained anabolic effects of long-term androgen administration in men with AIDS wasting.

Fifty-one human immunodeficiency virus-positive men with hypogonadism and wasting were randomized to receive testosterone enanthate, 300 mg i.m. every 3 weeks, or placebo for 6 months, followed by open-label testosterone administration for 6 months. Subjects initially randomized to placebo gained lean body mass (LBM) only after crossover to testosterone administration (mean change +/- standard error of the mean, -0.6 +/- 0.7 kg [months 0-6] vs. 1.9 +/- 0.7 kg [months 6-12]; P = .03). In contrast, subjects initially randomized to testosterone continued to gain LBM during open-label administration (2.0 +/- 0.7 kg [months 0-6] vs. 1.6 +/- 0.6 kg [months 6-12]; P = .62) and had gained more LBM at 1 year than did subjects receiving testosterone for only the final 6 months of the study (3.7 +/- 0.8 kg vs. 1.0 +/- 1.0 kg; P = .05). Testosterone administration results in sustained increases in LBM during 1 year of therapy in hypogonadal men with AIDS wasting.

Cross-Over Studies↗

Differential distribution of inositol trisphosphate receptor isoforms in mouse oocytes.

In mammalian fertilization, inositol 1,4,5-trisphosphate receptor (IP3R)-dependent Ca2+ release is a crucial signaling event that originates from the vicinity of sperm-egg interaction and spreads as a wave throughout the egg cytoplasm. While it is known that Ca2+ is released by the type 1 IP3R in the egg cortex, the potential involvement of other isoform types responsible for the Ca2+ rise in the mouse egg (interior) and their spatial distribution are not known. In addition, the biochemical basis has not been definitively established for the development of increased sensitivity to inositol 1,4,5-trisphosphate (IP3) during meiotic maturation. Using specific antibodies to the type 1, 2, and 3 IP3R, we tested the hypotheses that different IP3R isoforms are responsible for the internal Ca2+ elevation and that they contribute to the maturation-associated acquisition of IP3 sensitivity. In both preovulatory oocytes and ovulated eggs of CF-1 mice, immunofluorescence revealed that types 1 and 2 isoforms were present in the cell cortex and interior. Type 1 was observed throughout the cytoplasm, and Western analysis indicated a 1.9-fold maturation-associated increase. In contrast, the signals detected for the type 2 (high-affinity) isoform and type 3 were present to a lesser extent, with type 2 restricted to isolated islands (similar to aggregates of vesicles detected by electron microscopy), which, in the cortex, may amplify early sperm-egg signaling events. The cortical-to-perinuclear localization of the receptor and cortical vesicle aggregates imply an efficient mechanism for propagating Ca2+ release from the cortex into the interior of the egg to activate development, and the isoform localization analysis indicates a clear spatial and biochemical heterogeneity. Types 1 and 2 isoforms were also present in granulosa cells.

Amino Acid Sequence↗

Utilisation of prophylactic mastectomy in 10 European centres.

Increasingly women at high risk of breast cancer are opting for prophylactic surgery to reduce their risks. Data from 10 European centres that offer a risk counselling and screening service to women at risk show different approaches to the option of preventive surgery, although most centres adhere to a protocol including at least two risk counselling sessions and a psychological assessment. Thus far the combined centres have data on 174 women who have undergone prophylactic mastectomy with in excess of 400 women years of follow up. Operations were carried out on women with lifetime risks of 25-80%, with an average annual expected incidence rate of 1% per women. No breast cancers have occurred in this cohort. Long term follow up on an extended group of women will be necessary to truly address the risk of subsequent breast cancer and the psychological sequelae.

Adult↗

Efficacy of early diagnosis and treatment in women with a family history of breast cancer. European Familial Breast Cancer Collaborative Group.

BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality. METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan-Meier survival plots. RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first ("prevalence") round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+. CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of "breast awareness" as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families.

Adult↗