Biomedical subjects
R Simmons
Publications and source records attributed to R Simmons.
Fibrin sealant reduces the duration and amount of fluid drainage after axillary dissection: a randomized prospective clinical trial.
BACKGROUND: Patients who have axillary dissections during lumpectomy or modified radical mastectomy for breast carcinoma accumulate serosanguinous fluid, potentially resulting in a seroma. Currently accepted practice includes insertion of one or more drains for fluid evacuation. This multicenter, randomized, controlled, phase II study was undertaken to evaluate whether a virally inactivated, investigational fibrin sealant is safe and effective when used as a sealing agent to reduce the duration and volume of serosanguinous fluid drainage and to determine the dose response of this effect. STUDY DESIGN: Patients undergoing lumpectomy or modified radical mastectomy were randomized to treatment with 4, 8, or 16 mL of fibrin sealant or control (no agent) at the axillary dissections site. Patients undergoing modified radical mastectomy also received an additional 4 or 8 mL of fibrin sealant at the skin flap site. Efficacy was evaluated by the number of days required for wound drainage and the volume of fluid drainage compared with control. Safety was confirmed by clinical course, the absence of viral seroconversion, and no major complications attributable to the sealant. RESULTS: The 4-mL axillary dissection dose of fibrin sealant significantly reduced the duration and quantity of fluid drainage from the axilla following lumpectomy (p < or = 0.05). In the modified radical mastectomy patients, a 16-mL axillary dissection dose combined with an 8-mL skin flap dose was significantly effective in reducing the number of days to drain removal (p < or = 0.05) and fluid drainage (p < or = 0.01). There were no fibrin sealant patient viral seroconversions and no major complications attributable to the sealant. A number of wound infections were noted, although this may represent a center-specific effect. CONCLUSIONS: Application of fibrin sealant following axillary dissection at the time of lumpectomy or modified radical mastectomy can significantly decrease the duration and quantity of serosanguinous drainage. The viral safety of the product was also supported.
The effect of neighborhood-based community organizing: results from the Seattle Minority Youth Health Project.
OBJECTIVE: To evaluate the effect of a community mobilization and youth development strategy to prevent drug abuse, violence, and risky sexual activity. DATA SOURCES/STUDY SETTING: Primary surveys of youth, parents, and key neighborhood leaders were carried out at baseline (1994) and at the end of the intervention period (1997). The study took place in four intervention and six control neighborhoods in Seattle. STUDY DESIGN: The study was designed as a randomized controlled trial with neighborhood as the unit of randomization. The intervention consisted of a paid community organizer in each neighborhood who recruited a group of residents to serve as a community action board. Key variables included perceptions of neighborhood mobilization by youth, parents, and key neighborhood leaders. DATA COLLECTION/EXTRACTION METHODS: Youth surveys were self-administered during school hours. Parent and neighborhood leader surveys were conducted over the phone by trained interviewers. PRINCIPAL FINDINGS: Survey results showed that mobilization increased to the same degree in both intervention and control neighborhoods with no evidence of an overall intervention effect. There did appear to be a relative increase in mobilization in the neighborhood with the highest level of intervention activity. CONCLUSION: This randomized study failed to demonstrate a measurable effect for a community mobilization intervention. It is uncertain whether the negative finding was because of a lack of strength of the interventions or problems detecting intervention effects using individual-level closed-end surveys.
Bone marrow micrometastases in breast cancer patients.
BACKGROUND: The status of the axillary nodes has historically been the most important indicator of prognosis in breast cancer patients. However, approximately one third of node-negative patients recur with systemic disease. The detection of bone marrow micrometastases (BMM) may represent additional information in predicting distant recurrence and survival. METHODS: Bone marrow aspiration is obtained from the patient's anterior iliac crest at the time of breast cancer surgery. Cytospins are prepared from this aspirate and stained for polymerase chain reaction (PCR) analysis. RESULTS: Multiple studies have evaluated the clinical implications of BMM. The majority of studies have found a significant correlation between the presence of BMM and decreased survival. The information of bone marrow status may serve as a complement to axillary lymph node status in assessing the prognosis of breast cancer patients. CONCLUSIONS: There is a strong correlation between the presence of bone marrow micrometastases and poorer survival. These results may have an impact upon therapeutic recommendations in breast cancer patients.
Leadership behaviour similarity as a basis of selection into a management team.
There are contexts where, in order to be effective, a management team needs to display different leadership behaviours as well as possessing a wide range of experiences and skills. But achieving heterogeneity of behaviours is difficult if there are behavioural-similarity biases affecting a selection process. A sample of 126 participants completed a simulation of a selection process for a management team. They compared selection criteria and chose either a task or relations-oriented applicant for an advertised position as well as reporting their perception of their own preferred leadership style. The results of the simulation indicate that leadership behaviour can be a basis for similarity-attraction in the selection of a management team.
Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study.
We have used optical tweezers to study the elasticity of red cell membranes; force was applied to a bead attached to a permeabilized spherical ghost and the force-extension relation was obtained from the response of a second bead bound at a diametrically opposite position. Interruption of the skeletal network by dissociation of spectrin tetramers or extraction of the actin junctions engendered a fourfold reduction in stiffness at low applied force, but only a twofold change at larger extensions. Proteolytic scission of the ankyrin, which links the membrane skeleton to the integral membrane protein, band 3, induced a similar effect. The modified, unlike the native membranes, showed plastic relaxation under a prolonged stretch. Flaccid giant liposomes showed no measurable elasticity. Our observations indicate that the elastic character is at least as much a consequence of the attachment of spectrin as of a continuous membrane-bound network, and they offer a rationale for formation of elliptocytes in genetic conditions associated with membrane-skeletal perturbations. The theory of Parker and Winlove for elastic deformation of axisymmetric shells (accompanying paper) allows us to determine the function BH(2) for the spherical saponin-permeabilized ghost membranes (where B is the bending modulus and H the shear modulus); taking the literature value of 2 x 10(-19) Nm for B, H then emerges as 2 x 10(-6) Nm(-1). This is an order of magnitude higher than the value reported for intact cells from micropipette aspiration. Reasons for the difference are discussed.
Contraceptive introduction reconsidered: a new methodology for policy and program development.
Although new contraceptive technology has the potential for providing women with expanded options for fertility control, the historical record of international family planning shows that, in practice, introduction of new methods has not always broadened reproductive choice. Using the example of introduction of intrauterine devices into the Indian family planning program in the 1960s, we show that an exclusive focus on the technology itself is problematic and argue that methodologies are needed that relate introduction of new methods to user needs and program capacities. We summarize key findings from the Indonesian experience with Norplant introduction. Although an effort was made to address problems with previous approaches, major deficiencies in both the technical and interpersonal dimensions of care arose when the implants were made broadly available within the program. We subsequently present a methodology for contraceptive introduction developed by the World Health Organization. This methodology emphasizes the social and institutional context in which technology is used and suggests a participatory and research-based approach to program and policy development. We illustrate results from this new approach in its implementation in Vietnam and suggest areas for further evaluation.
When is research participatory? Reflections on a reproductive health project in Brazil.
This article addresses women's participation in an organization development project designed to improve public sector family planning and reproductive health services in Brazil. Although community women collaborated in aspects of the intervention and research, the project nonetheless raises the basic question whether such involvement of community women does or does not correspond to what scientific writers consider to be the essence of participatory research. We review key project features in the context of recent literature and conclude that although the project is committed to the sharing of power and control, it does not fully correspond to the characteristics of participatory research. Moreover, we argue that given the project's central focus on reproductive health outcomes, complete adherence to the process-oriented, pure version of participatory research would have been inappropriate.
Expanding contraceptive choice: findings from Brazil.
This article presents findings from a participatory action research project in a municipality in southern Brazil that models a new and holistic approach to broadening women's contraceptive choices. The project encourages a collaborative process between researchers, community members, and public health managers to diagnose service-delivery problems, to design and implement interventions, and to evaluate their effectiveness. Findings from the baseline evaluation revealed major constraints in availability of and access to family planning and reproductive health services for women, as well as severe deficiencies in quality of care. Interventions designed to address these weaknesses, bound by the limited resources of the public sector, focused on training, restructuring of providers' roles and service-delivery patterns, the management process, the creation of a referral center, and the introduction of injectables, vasectomy services, and a program for adolescents. Evaluation results show the project's considerable impact in broadening reproductive options, although not all issues, especially those related to sustainability, have been resolved.
Women's fears and men's anxieties: the impact of family planning on gender relations in northern Ghana.
The Navrongo experiment, a family planning and health project in northern Ghana, has demonstrated that an appropriately designed, community-based family planning program can produce a change in contraceptive practice that had been considered unattainable in such a setting. Simultaneously, however, evidence suggests that newly introduced family planning services and contraceptive availability can activate tension in gender relations. In this society, where payment of bridewealth signifies a woman's requirement to bear children, there are deeply ingrained expectations about women's reproductive obligations. Physical abuse and reprisals from the extended family pose substantial threats to women; men are anxious that women who practice contraception might be unfaithful. Data from focus-group discussions with men and women are examined in this report and highlight the strains on gender relations resulting from contraceptive use. The measures taken to address this problem and methods of minimizing the risk of adverse social consequences are discussed.
Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation.
Noninfectious lung injury is common after allogeneic bone marrow transplantation (BMT), but its association with acute graft-versus-host disease (GVHD) is unclear. Using a murine BMT system where donor and host differ by multiple minor histocompatibility (H) antigens, we investigated the nature of lung injury and its relationship both to systemic GVHD and host-reactive donor T cells. Lethally irradiated CBA hosts received syngeneic BMT or allogeneic (B10.BR) T-cell-depleted (TCD) bone marrow (BM) with and without the addition of T cells. Six weeks after BMT, significant pulmonary histopathology was observed in animals receiving allogeneic BMT compared with syngeneic controls. Lung damage was greater in mice that received allogeneic T cells and developed GVHD, but it was also detectable after TCD BMT when signs of clinical and histologic acute GVHD were absent. In each setting, lung injury was associated with significant alterations in pulmonary function. Mature, donor (Vbeta6(+) and Vbeta3(+)) T cells were significantly increased in the broncho-alveolar lavage (BAL) fluid of all allogeneic BMT recipients compared with syngeneic controls, and these cells proliferated and produced interferon-gamma (IFN-gamma) to host antigens in vitro. These in vitro responses correlated with increased IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in the BAL fluid. We conclude that alloreactive donor lymphocytes are associated with lung injury in this allogeneic BMT model. The expansion of these cells in the BAL fluid and their ability to respond to host antigens even when systemic tolerance has been established (ie, the absence of clinical GVHD) suggest that the lung may serve as a sanctuary site for these host reactive donor T cells. These findings may have important implications with regard to the evaluation and treatment of pulmonary dysfunction after allogeneic BMT even when clinical GVHD is absent.
Evidence for the inactivation of multiple replicative lifespan genes in immortal human squamous cell carcinoma keratinocytes.
Human keratinocyte immortality is genetically recessive to the normal phenotype of limited replicative lifespan and appears to require the dysfunction of p53 and the cyclin D-Cdk inhibitor p16. In order to test for the inactivation of other candidate replicative lifespan genes in the immortal cells of human tumors, we developed a series of mortal and immortal keratinocyte cultures derived from neoplastic lesions of the head and neck which were amenable to molecular genetic analysis by the loss of heterozygosity (LOH) technique. The results indicate that keratinocyte immortalization in head and neck squamous cell carcinoma (SCC-HN) development involves the inactivation of at least two further pathways to senescence and four in all. Chromosomes 1, 4 and 7 carry genes representing immortality complementation groups C, B and D respectively and immortal keratinocytes showed LOH at either 4q32-q34 between D4S1554 and D4S171 (group B) or 7q31 (group D) but never 1q25 (group C). These results tentatively suggest that the genes responsible for the immortality complementation groups encode proteins on the same pathway to senescence. In addition, all of the immortal keratinocyte lines possessed high levels of telomerase activity and a suppressor of telomerase activity has been mapped to the short arm of chromosome 3p. Five out of eight lines showed LOH at 3p21.2-p21.3, a region which may carry a gene capable of suppressing SCC-HN telomerase. However, alternative mechanisms of telomerase reactivation were also suggested by our results. None of the above genetic alterations were seen in seven senescent neoplastic keratinocyte cultures. Other loci harbouring antiproliferative genes implicated in replicative lifespan showed few or no alterations and any alterations seen were additional to those described above.
The strategic approach to contraceptive introduction.
The introduction of new contraceptive technologies has great potential for expanding contraceptive choice, but in practice, benefits have not always materialized as new methods have been added to public-sector programs. In response to lessons from the past, the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (HRP) has taken major steps to develop a new approach and to support governments interested in its implementation. After reviewing previous experience with contraceptive introduction, the article outlines the strategic approach and discusses lessons from eight countries. This new approach shifts attention from promotion of a particular technology to an emphasis on the method mix, the capacity to provide services with quality of care, reproductive choice, and users' perspectives and needs. It also suggests that technology choice should be undertaken through a participatory process that begins with an assessment of the need for contraceptive introduction and is followed by research and policy and program development. Initial results from Bolivia, Brazil, Burkina Faso, Chile, Myanmar, South Africa, Vietnam, and Zambia confirm the value of the new approach.
Transplantation of polarized type 2 donor T cells reduces mortality caused by experimental graft-versus-host disease.
Acute graft-versus-host disease (GVHD) is thought to be initiated by alloreactive type 1 T cells that secrete gamma-interferon (IFN-gamma). IFN-gamma induces the production of inflammatory cytokines, e.g., tumor necrosis factor-alpha and interleukin (IL)-1, which are the distal mediators of GVHD. We demonstrate that the transplantation of polarized type 2 murine T cells (i.e., cells secreting IL-4 but not IFN-gamma) together with T-cell-depleted bone marrow results in a significant increase in survival (P<0.001) after bone marrow transplantation across minor histocompatibility barriers (B10.BR-->CBA/J). Further analysis demonstrated that increased survival in recipients of polarized type 2 T cells correlated with diminished production of both IFN-gamma and tumor necrosis factor-alpha but with increases in IL-4 2 weeks after transplantation. Despite improved survival, histologic changes of GVHD were evident in oral mucosal and hepatic tissues at 7 weeks after bone marrow transplantation. These data provide further evidence that inflammatory cytokines in the immediate posttransplant period are pivotal to the development of mortality but that they do not correlate with individual target organ damage.
Molecular motors: single-molecule mechanics.
Novel techniques are revealing the movements and forces associated with single interactions of motor proteins, such as myosin and kinesin, and also of processive enzymes, such as RNA polymerase.
Single-molecule mechanics.
Novel techniques are revealing the movements and forces associated with single interactions of motor proteins, such as myosin and kinesin, and also of processive enzymes, such as RNA polymerase.
Evaluation and management of bilateral renal artery stenosis in children: a case series and review.
This report describes the clinical course, diagnostic evaluation and management of six children with bilateral renal artery stenosis (RAS) and concurrent narrowing of the abdominal aorta. Except for one child with active arteritis, the others were asymptomatic. There were no clinical or laboratory features suggesting the etiology of hypertension in four of six patients, and diagnostic procedures, including Doppler duplex ultrasound and captopril scintigraphy, were unreliable in screening for such hypertension. Abdominal aortography and selective renal angiography confirmed the diagnosis of bilateral RAS and associated anatomical alterations of the aorta and its branches. The hypertension was severe and minimally responsive to antihypertensive agents. It was cured or improved after percutaneous transluminal angioplasty (PTA) of three vessels in two children with mid-vessel stenoses, while hypertension persisted after PTA of two mid-vessel stenoses in a third child and one vessel with ostium stenosis in a fourth child. Autotransplantation of seven kidneys in four children resulted in cure of significant improvement of the hypertension. Renal function was preserved in all children during a mean follow-up time of 41 months. Based on illustrative data from these six children, as well as information from a review of the literature, this report discusses the key diagnostic issues and stresses the potential advantages of renal autotransplantation in selected children with this disorder.