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Biomedical subjects

S Ellis

Publications and source records attributed to S Ellis.

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

Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting.

BACKGROUND: Although the frequency of restenosis after coronary angioplasty is reduced by stenting, when restenosis develops within a stent, the risk of subsequent restenosis is greater than 50 percent. We report on a multicenter, double-blind, randomized trial of intracoronary radiation therapy for the treatment of in-stent restenosis. METHODS: Of 252 eligible patients in whom in-stent restenosis had developed, 131 were randomly assigned to receive an indwelling intracoronary ribbon containing a sealed source of iridium-192, and 121 were assigned to receive a similar-appearing nonradioactive ribbon (placebo). RESULTS: The primary end point, a composite of death, myocardial infarction, and the need for repeated revascularization of the target lesion during nine months of follow-up, occurred in 53 patients assigned to placebo (43.8 percent) and 37 patients assigned to iridium-192 (28.2 percent, P=0.02). However, the reduction in the incidence of major adverse cardiac events was determined solely by a diminished need for revascularization of the target lesion, not by reductions in the incidence of death or myocardial infarction. Late thrombosis occurred in 5.3 percent of the iridium-192 group, as compared with 0.8 percent of the placebo group (P=0.07), resulting in more late myocardial infarctions in the iridium-192 group (9.9 percent vs. 4.1 percent, P=0.09). Late thrombosis occurred in irradiated patients only after the discontinuation of oral antiplatelet therapy (with ticlopidine or clopidogrel) and only in patients who had received new stents at the time of radiation treatment. CONCLUSIONS: Intracoronary irradiation with iridium-192 resulted in lower rates of clinical and angiographic restenosis, although it was also associated with a higher rate of late thrombosis, resulting in an increased risk of myocardial infarction. If the problem of late thrombosis within the stent can be overcome, intracoronary irradiation with iridium-192 may become a useful approach to the treatment of in-stent restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2001

HLA-G remains a mystery.

In this brief summary, we argue that many widely held beliefs about HLA-G are questionable. Recent research has led to a re-evaluation of many of the characteristics that were thought to make HLA-G unusual among the MHC class I molecules. First, contrary to reports suggesting that the gene encoding HLA-G exhibits marked polymorphism in some human populations, recent data have shown that the HLA-G gene has comparatively little polymorphism - a feature that might allow it to be expressed in the placenta without causing rejection by the maternal immune system. Second, although truncated forms of HLA-G are generated in the placenta, most of them are unlikely to have significant biological effects as they do not reach the cell surface. Third, the hypothesis that a major role of HLA-G is to prevent attack of the placenta by maternal natural killer cells is now the subject of renewed scrutiny. Finally, there is little evidence that the induction of expression of HLA-G is a major mechanism by which tumor cells avoid immune attack. HLA-G has once again become as mysterious as when it was discovered: an MHC class I molecule expressed at a challengingly extraordinary site--the immunologically uneasy interface between mother and fetus.

Animals↗
PubMed2001

The non-peptidyl fungal metabolite L-783,281 activates TRK neurotrophin receptors.

Neurotrophin binding to the extracellular surface of the Trk family of tyrosine kinase receptors leads to the activation of multiple signalling cascades, culminating in neuroregenerative effects, including neuronal survival and neurite outgrowth. Since neurotrophins themselves are not ideal drug candidates due to their poor pharmacokinetic behaviour and bioavailability, small molecule neurotrophin mimetics may be beneficial in treating a number of neurodegenerative disorders. The present study demonstrates that L-783,281, a non-peptidyl fungal metabolite, is capable of stimulating TrkA, B and C phosphorylation to various extents in CHO cells stably expressing human Trk receptors. L-783,281 also stimulated Trk phosphorylation in a number of rat and human primary neuronal cultures, whereas the highly similar compound, L-767,827, was without effect. Mechanistic studies utilizing transiently transfected PDGF/TrkA and TrkA/PDGF chimeras, demonstrated that L-783,281 is likely to interact with the intracellular domain of the TrkA receptor. Further investigations suggested that L-783,281 was nevertheless able to instigate receptor dimerization by binding in a non-covalent manner. Although the cytotoxicity of the compound was shown to preclude its effects in neuronal survival and neurite outgrowth assays, it is a prototype for a small molecule neurotrophin mimetic that activates Trk by interacting at a site different from the neurotrophin-binding site.

Animals↗
PubMed2001

Impact of the Duett sealing device on quality of life and hospitalization costs for coronary diagnostic and interventional procedures: Results from the Study of Economic and Quality of Life substudy of the SEAL trial.

BACKGROUND: The Simple and Effective Arterial Closure (SEAL) trial examined the safety and effectiveness of the Duett vascular sealing device (Vascular Solutions, Minneapolis, Minn) versus manual compression after diagnostic and interventional coronary procedures. We compared quality of life and initial hospitalization costs among patients treated with the Duett device versus manual compression. METHODS: Functional status was assessed with the Duke Activity Status Index (DASI) at 7 and 30 days after intervention. General health status was assessed with the Short Form (SF-36) at 30 days after intervention. Hospitalization costs were derived from the UB92 formulation of the hospital bill. RESULTS: There was a strong trend toward higher functional status in patients receiving treatment with the Duett device at 7 days both before (P =.04) and after (P =.08) adjustment for significant covariates. This difference was significant in the diagnostic group but not in the interventional group. No significant differences in quality of life between the Duett device and manual compression at 30 days were found. There was no significant difference in total hospitalization costs between treatment arms (P =.91). For interventional patients, mean total in-hospital costs were $10,167 in the Duett group and $10,225 in the manual compression group (P =.82). For diagnostic patients, mean hospitalization costs were $7784 and $7996 for the Duett device and manual compression groups, respectively (P =.72). Trends toward reduced recovery/observation room costs with the Duett device (P =.06) were found; this difference was significant in the diagnostic group ($198 vs $279, P =.02). CONCLUSIONS: The Duett sealing device was associated with significantly higher functional status at 7 days after the procedure in addition to shortened time to hemostasis and ambulation, with no associated increase in cost.

Adult↗
PubMed2001

Review of studies establishing the aging male spontaneously hypertensive rat as a detector and quantifier of the kidney toxicity of radiocontrast media and other chemicals.

RATIONALE AND OBJECTIVES: There is a need for practical and sensitive preclinical tests for detecting the kidney toxicity of chemicals. The spontaneously hypertensive rat (SHR), as it ages, develops renal and cardiovascular changes similar to those considered as human risk factors for radiocontrast-induced renal damage. Age, male gender, and uncontrolled hypertension make these animals susceptible to the volume and osmolality of the administered contrast agent and the effect of repeated contrast administration after a brief interval. This article reviews studies in which the role of these and other factors were evaluated to validate the male SHR as a small animal model for renal damage induced by contrast and other agents. METHODS: Systolic blood pressure was measured with a tail cuff before and after the administration of the experimental substances, and the left kidney and heart were studied histologically to determine the influence of age, dose of contrast repeated at a short interval, gender and strain, the role of the sympathetic adrenergic nervous system, osmolality, and apoptosis. RESULTS: As the animals aged and the systolic blood pressure remained elevated, the animals developed progressive renal lesions that worsened after the administration of contrast. The most advanced renal lesions occurred in adult male SHRs that received two doses of contrast 6 hours apart. Female SHR rats and male Wistar Kyoto rats showed no effect or only minimal changes in heart and kidneys after the administration of contrast compared with age-matched male SHRs. Adrenergic blockade allowed only a small elevation in systolic blood pressure after contrast administration but did not protect the kidneys against renal damage by contrast. Hypaque, Omnipaque, and mannitol caused renal damage in proportion to their osmolality. Apoptosis with Hypaque, Omnipaque, and mannitol was observed in the kidney and heart. CONCLUSION: The results indicate that the aging male SHR develops spontaneous renal lesions that progress with age, increasing the susceptibility to the renal-damaging effects of contrast. Thus, the aging male SHR provides a laboratory tool for detecting the risk of renal damage of new contrast media as well as other pharmaceuticals and assessing methods to protect the kidneys and possible mechanisms of renal damage.

Age Factors↗
PubMed2001

Can clinical pharmacists affect SF-36 scores in veterans at high risk for medication-related problems?

BACKGROUND: An objective of pharmaceutical care is for pharmacists to improve patients' health-related quality of life (HRQOL) by optimizing medication therapy. OBJECTIVES: The objective of this study was to determine whether ambulatory care clinical pharmacists could affect HRQOL in veterans who were likely to experience a drug-related problem. RESEARCH DESIGN: This was a 9-site, randomized, controlled trial involving Veterans Affairs Medical Centers (VAMCs). Patients were eligible if they met > or = 3 criteria for being at high risk for drug-related problems. Enrolled patients were randomized to either usual medical care or usual medical care plus clinical pharmacist interventions. HRQOL was measured with the SF-36 questionnaire administered at baseline and at 6 and 12 months. RESULTS: In total, 1,054 patients were enrolled; 523 were randomized to intervention, and 531 to control. After patient age, site, and chronic disease score were controlled for, the only domain that was significantly different between groups over time was the bodily pain scale, which converged to similar values at the end of the study. Patients' rating of the change in health status in the past 12 months was statistically different between groups, intervention patients declining less (-2.4 units) than control subjects (-6.3 units) (P < 0.004). This difference was not considered clinically meaningful. However, a dose-response relationship was observed for general health perceptions (P = 0.004), vitality (P = 0.006), and change in health over the past year (P = 0.007). CONCLUSIONS: These results suggest that clinical pharmacists had no significant impact on HRQOL as measured by the SF-36 for veterans at high risk for medication-related problems.

Aged↗
PubMed2001

Linkage of reproductive sciences: from 'quick fix' to 'integrated' conservation.

Our laboratory has experienced four phases in understanding how the reproductive sciences contribute to genuine conservation of biodiversity. The first is the 'quick fix phase' in which the erroneous assumption is made that extant knowledge and techniques are readily adaptable to an unstudied wild animal to produce offspring rapidly. The second is the 'species-specificity phase' in which it is recognized that every species has evolved unique reproductive mechanisms that must be mastered before propagation can be enhanced. The third is the 'applicability phase' in which one grasps that all the new knowledge and technology are of minimal relevance without the cooperation of wildlife managers. The final phase is 'integration', the realization that reproduction is only one component in an abundantly complex conservation puzzle that requires interweaving many scientific disciplines with elaborate biopolitical, economic and habitat variables. These phases are illustrated using 20 years of experience with wildlife species, including the cheetah, black-footed ferret and giant panda. We conclude that the foremost value of the reproductive sciences for conserving endangered species is the discipline's powerful laboratory tools for understanding species-specific reproductive mechanisms. Such scholarly information, when applied holistically, can be used to improve management by natural or, occasionally, assisted breeding. Genuine conservation is achieved only when the reproductive knowledge and technologies are integrated into multidisciplinary programmes that preserve species integrity ex situ and preferably in situ.

Acinonyx↗
PubMed2000

The novel Rho-family GTPase rif regulates coordinated actin-based membrane rearrangements.

Small GTPases of the Rho family have a critical role in controlling cell morphology, motility and adhesion through dynamic regulation of the actin cytoskeleton [1,2]. Individual Rho GTPases have been shown to regulate distinct components of the cytoskeletal architecture; RhoA stimulates the bundling of actin filaments into stress fibres [3], Rac reorganises actin to produce membrane sheets or lamellipodia [4] and Cdc42 causes the formation of thin, actin-rich surface projections called filopodia [5]. We have isolated a new Rho-family GTPase, Rif (Rho in filopodia), and shown that it represents an alternative signalling route to the generation of filopodial structures. Coordinated regulation of Rho-family GTPases can be used to generate more complicated actin rearrangements, such as those underlying cell migration [6]. In addition to inducing filopodia, Rif functions cooperatively with Cdc42 and Rac to generate additional structures, increasing the diversity of actin-based morphology.

Actins↗
PubMed2000

Impact of patient characteristics, complications, and facility volume on the costs and time of cardiac catheterization and coronary angioplasty in 70 catheterization laboratories.

Although over 1 million procedures are performed in cardiac catheterization laboratories (CCLs) annually, little comparative data exist on costs or resource use in these settings. In this study, data from 70 CCLs were used to profile CCL times and total direct costs for 2 high-volume procedures: left heart catheterization (LHC) and percutaneous transluminal coronary angioplasty (PTCA) with or without stent placement. In total, 70,677 consecutive patient examinations for a 12-month period from January 1, 1998 to December 31, 1998 were analyzed. For LHC mean total direct costs averaged $306, whereas for PTCA catheterization laboratory costs averaged $3,172. The average total times for these procedures were 63 and 108 minutes, respectively. Seventy-two percent of the PTCA patients underwent coronary stenting with an associated incremental cost of $1,244. By multivariate linear regression, baseline patient characteristics such as age, gender, and clinical factors had little impact on total time and total costs. The major determinants of CCL time and cost were procedural factors (e.g., number and type of interventions) and in-lab complications, including profound hypotension, abrupt vessel closure, and emergency bypass surgery. Using facility procedure volume as a proxy for potential economies of scale, we found no relation between CCL volume and total direct CCL costs. There did appear to be a significant inverse relation between facility volume and total procedural time with CCLs that performed the highest volumes of LHC and PTCA procedures saving an average of 5 to 9 minutes per procedure. These findings may be useful in defining specific time and cost benchmarks for these commonly performed procedures and serve to underscore the critical role of reducing complications in both quality improvement and cost-saving efforts.

Aged↗
PubMed2000

Adherence to pharmacological interventions. Current trends and future directions. The Pharmacological Intervention Working Group.

The complexity of adherence to pharmacological interventions is frequently underestimated. Consequently, little research has been done to understand, improve, or evaluate the effects of adherence to drug protocols. While efforts to better measure and increase adherence require dedicated resources, improved adherence in existing clinical research can potentially cut costs in trial size and length. This paper outlines strategies to facilitate research on adherence to pharmacological interventions including: reporting of adherence data, changing how we conceptualize adherence to pharmaceuticals, understanding issues unique to older adults' pill-taking behavior, and creating standardized methodologies to measure adherence. Further, we describe some promising research areas that may lead to effective interventions: adherence "typologies" and modality matching. Control Clin Trials 2000;21:218S-225S

Aged↗
PubMed2000

Regulation of endocytic traffic by rho family GTPases.

Endocytosis is a complicated yet highly efficient process that involves the uptake and processing of cargoes, ranging from small molecules, to activated signalling receptors, to whole microorganisms. Regulation of endocytic pathways is poorly understood. Recent evidence suggests that the Rho GTPase family of signalling proteins is intimately involved in endocytic traffic, providing novel insights into the control mechanisms that govern this process.

3T3 Cells↗
PubMed2000

Outpatient morning report: a new educational venue.

Increasingly, medical educators are looking for ways to train residents and medical students in outpatient medicine. One novel idea, outpatient morning report, draws upon the concept of inpatient morning report and applies a similar conference format to the outpatient setting. The authors describe outpatient morning report and comment on its successful use in their institution.

Ambulatory Care↗
PubMed2000

Heat-induced alterations in the localization of HSP72 and HSP73 as measured by indirect immunohistochemistry and immunogold electron microscopy.

The heat shock proteins are a family of stress-inducible proteins that act as molecular chaperones for nascent proteins and assist in protection and repair of proteins whose conformation is altered by stress. HSP72 and HSP73 are two major cytosolic/nuclear stress proteins of mammalian cells, with extensive sequence homology. HSP73 is constitutively expressed, whereas HSP72 is highly stress-inducible. However, it is unclear why two isoforms are expressed and whether these two proteins have different functions in the cell. To assist in the delineation of function, we have completed a detailed study of the localization of HSP72 and HSP73 in the cell before and after heat stress, using two different methods of detection. By indirect immunohistochemistry, the localization of these two proteins is similar, cytoplasmic and nuclear in nonstressed cells with a translocation to nucleoli immediately after heat. By the more sensitive immunogold electron microscopy technique, differences in localization were noted. In nonstressed cells, HSP72 was primarily nuclear, localized in heterochromatic regions and in nucleoli. HSP73 was distributed throughout the cell, with most cytoplasmic label associated with mitochondria. Mitotic chromosomes were also heavily labeled. After stress, HSP72 concentrated in nuclei and nucleoli and HSP73 localized to nuclei, nucleoli, and cytoplasm, with increased label over mitochondria. These differences in localization suggest that the HSP72 and HSP73 may associate with different proteins or complexes and hence have different but overlapping functions in the cell.

Animals↗
PubMed2000

Development of chick axial mesoderm: specification of prechordal mesoderm by anterior endoderm-derived TGFbeta family signalling.

Two populations of axial mesoderm cells can be recognised in the chick embryo, posterior notochord and anterior prechordal mesoderm. We have examined the cellular and molecular events that govern the specification of prechordal mesoderm. We report that notochord and prechordal mesoderm cells are intermingled and share expression of many markers as they initially extend out of Hensen's node. In vitro culture studies, together with in vivo grafting experiments, reveal that early extending axial mesoderm cells are labile and that their character may be defined subsequently through signals that derive from anterior endodermal tissues. Anterior endoderm elicits aspects of prechordal mesoderm identity in extending axial mesoderm by repressing notochord characteristics, briefly maintaining gsc expression and inducing BMP7 expression. Together these experiments suggest that, in vivo, signalling by anterior endoderm may determine the extent of prechordal mesoderm. The transforming growth factor (beta) (TGFbeta) superfamily members BMP2, BMP4, BMP7 and activin, all of which are transiently expressed in anterior endoderm mimic distinct aspects of its patterning actions. Together our results suggest that anterior endoderm-derived TGFbetas may specify prechordal mesoderm character in chick axial mesoderm.

Activins↗
PubMed2000

An economic analysis of a randomized, controlled, multicenter study of clinical pharmacist interventions for high-risk veterans: the IMPROVE study. Impact of Managed Pharmaceutical Care Resource Utilization and Outcomes in Veterans Affairs Medical Centers.

STUDY OBJECTIVE: To determine if clinical pharmacists could affect economic resource use and humanistic outcomes in an ambulatory, high-risk population. DESIGN: Prospective, randomized, controlled study. SETTING: Nine Veterans Affairs medical centers. PATIENTS: Patients who were at high risk for medication-related problems. INTERVENTION: Patients were randomized to usual medical care with input from a clinical pharmacist (intervention group) or just usual medical care (control group). MEASUREMENTS AND MAIN RESULTS: Of 1,054 patients enrolled, 523 were randomized to the intervention group and 531 to the control group. The number of clinic visits increased in the intervention group (p=0.003), but there was no difference in clinic costs. Mean increases in total health care costs were $1,020 for the intervention group and $1,313 for the control group (p=0.06). CONCLUSION: Including the cost of pharmacist interventions, overall health care expenditures were similar for patients randomized to see a clinical pharmacist versus usual medical care.

Aged↗
PubMed2000

Growth and morphogenesis of epithelial cell organoids from peripheral and medial mammary parenchyma of prepubertal heifers.

Collagen gel cell cultures were used to test the hypothesis that cells from peripheral parenchymal zones of the developing bovine mammary gland have greater proliferative and morphogenic potential than cells from the medial parenchymal mass. Tritiated thymidine was incorporated to assess cell proliferation. Dose responses for insulin-like growth factor one (IGF-I, 0 to 50 ng/ml) and transforming growth factor beta one (0 to 5 ng/ml) were determined for each cell population. Cells from the peripheral regions were two to three times more sensitive to the mitogenic action of IGF-I or serum. Transforming growth factor beta one concentrations of 12.5 to 500 pg/ml stimulated cell proliferation, but concentrations above 1 ng/ml were inhibitory. Peripheral cells showed a distinct biphasic response to addition of transforming growth factor beta one. Morphology of organoids was evaluated daily during culture and by histologic examination at the end of culture. Peripheral zone cells formed multi-layered cell structures that resembled native mammary parenchyma with serum or mammary gland extract. Our results indicate that epithelial cells of the peripheral and medial parenchymal zones in the ruminant mammary gland can differ in their proliferative and morphogenetic response to growth factor treatment in vitro. These differences likely reflect local tissue regulation necessary for sequential ductular and lobulo-alveolar development in vivo.

Animals↗