Biomedical subjects
Publications and source records attributed to M Bishop.
The previous paper explored the meaning of ethics, especially its relationship to dentistry. Here, we examine a practical application for solving ethical problems. Together, the two articles should provide dentists with a core of relevant knowledge about ethics and a ready guide to the daily relevance of ethics.
This short series of two papers will examine the relationship between ethics and dentistry. The first paper explores the meaning of ethics; the second will provide a catalogue of primary sources for dental practitioners who wish to read further in order to gain a core of knowledge about dental ethics.
We have developed a novel way to use the Cre/loxP system for in vitro manipulation of DNA and a technique to clone DNA into circular episomes. The method is fast, reliable, and allowsflexible cloning of DNA fragments into episomes containing a loxP site. We show that a loxP site can serve as a universal target site to clone a DNA fragment digested with any restriction enzyme(s). This technique abolishes the need for compatible restriction sites in cloning vectors and targets by generating custom-designed 5' 3', or blunt ends in the desired orientation and reading frame in the vector Therefore, this method eliminates the limitations encountered when DNA fragments are cloned into vectors with a confined number of cloning sites. The 34-bp loxP sequence assures uniqueness, even when large episomes are manipulated. We present three examples, including the manipulation of a bacterial artificial chromosome. Because DNA manipulation takes place at a loxP site, we refer to this technique as loxP-directed cloning.
Here we describe a procedure for cloning pigs by the use of in vitro culture systems. Four healthy male piglets from two litters were born following nuclear transfer of cultured somatic cells and subsequent embryo transfer. The initiation of five additional pregnancies demonstrates the reproducibility of this procedure. Its important features include extended in vitro culture of fetal cells preceding nuclear transfer, as well as in vitro maturation and activation of oocytes and in vitro embryo culture. The cell culture and nuclear transfer techniques described here should allow the use of genetic modification procedures to produce tissues and organs from cloned pigs with reduced immunogenicity for use in xenotransplantation.
Development of CNS dysfunction in the setting of hematopoietic stem cell transplant (HSCT) has been previously shown to predict for subsequent second organ dysfunction and death. In this paper, we describe the characteristics of this isolated CNS dysfunction, and its relationship to multiple organ dysfunction syndrome (MODS) after HSCT. Twenty-one of 186 patients undergoing HSCT developed CNS dysfunction as their first organ dysfunction a mean of 22.8 +/- 0.9 days after the start of the preparative regimen. Compared with 137 patients who developed no organ dysfunction, patients presenting with CNS dysfunction were more likely to have undergone allogeneic HSCT (P = 0.001) and to have received a total body irradiation-based regimen (P = 0.001), and were less likely to have been transplanted for lymphoma (P = 0.008). Patients who developed CNS dysfunction were more likely to die than those with no organ dysfunction (P < 0. 001). Of the 21 patients who developed CNS dysfunction, 48% resolved their dysfunction by a mean of 4.6 days later without progression to second organ dysfunction, and 90% of these patients survived to day 100. Fifty-two percent of patients with CNS dysfunction progressed to second organ dysfunction (pulmonary or hepatic) a mean of 5.5 days later, and only 36% survived to day 100 (P = 0.02). The patients who progressed to second organ dysfunction and those who did not were not different in terms of type of HSCT (allogeneic vs autologous), stem cell source (blood vs bone marrow), age, diagnosis or preparative regimen. Development of CNS dysfunction in the setting of HSCT, as with other organ dysfunctions (such as hepatic veno-occlusive disease), probably represents an early manifestation of a systemic disorder predisposing for MODS, increasing the risk of transplant-related mortality. Early systemic therapies directed at modulating this systemic disorder are probably indicated. Bone Marrow Transplantation (2000) 25, 79-83.
This large, long-term study of families served by hospice found that nearly 95 percent said hospice had been helpful. Still, about 30 percent of family members said there was something they wish hospice had done differently. Those who had some complaint were more likely than those who had no complaints to be women, to report the patient had needed a great deal of care, to have a history of depression and greater levels of distress before and after the patient's death, and to be dissatisfied with the support they received from family members and friends.
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This study tested the hypothesis that coping through emotional approach, which involves actively processing and expressing emotions, enhances adjustment and health status for breast cancer patients. Patients (n = 92) completed measures within 20 weeks following medical treatment and 3 months later. Women who, at study entry, coped through expressing emotions surrounding cancer had fewer medical appointments for cancer-related morbidities, enhanced physical health and vigor, and decreased distress during the next 3 months compared with those low in emotional expression, with age, other coping strategy scores, and initial levels on dependent variables (except medical visits) controlled statistically. Expressive coping also was related to improved quality of life for those who perceived their social contexts as highly receptive. Coping through emotional processing was related to one index of greater distress over time. Analyses including dispositional hope suggested that expressive coping may serve as a successful vehicle for goal pursuit.
PURPOSE: The aim of this retrospective study was to review our experience of radiation therapy to regional nodes in patients with proven nodal metastases, with respect to regional control, late toxicity, and overall survival. METHODS AND MATERIALS: All patients with a histological diagnosis of malignant melanoma, with involvement of the regional nodes but without distant metastases, who commenced nodal irradiation between January 1985 and July 1995 at Peter MacCallum Cancer Institute were studied. The study population of 113 patients was divided into two categories: those with no residual macroscopic disease following nodal surgery (adjuvant group, 42 patients) and those who had no surgery (8) or had macroscopic residual disease following nodal surgery (63) (palliative group, 71 patients). RESULTS: In the adjuvant group at 5 years following commencement of nodal irradiation 26% were estimated to be failure-free. Of the 74% who had experienced treatment failure by 5 years, an estimated 20% failed first with nodal relapse, 52% with distant metastases, and 2% with both nodal relapse and distant metastases. The estimated 5-year overall survival for this group was 33%. In the palliative group 16 patients (23%) had an objective complete response. Altogether 48 patients (68%) had a symptomatic response. At 5 years the overall survival in this group was 8% and an estimated 4% were failure-free. Of the 96% who had failed by 5 years, 68% failed first in the regional nodes, 25% had distant metastases as the first failure, and 3% had both nodal relapse and distant metastases. CONCLUSION: We recommend adjuvant postoperative radiation therapy for patients with proven nodal metastases and high risk of regional recurrence (multiple nodes, extracapsular extension, or recurrent nodal disease) in addition to adjuvant interferon.
Plasminogen related growth factors (PRGFs) and their receptors play major roles in embryogenesis, tissue regeneration and neoplasia. In order to investigate the complexity and evolution of the PRGF receptor family we have cloned and sequenced three receptors for PRGFs in the teleost fish Fugu rubripes, a model vertebrate with a compact genome. One of the receptor genes isolated encodes the orthologue of mammalian MET, whilst the other two may represent Fugu rubripes orthologues of RON and SEA. This is the first time three PRGF receptors have been identified in a single species.
Polymorphic microsatellites have been developed in the vicinity of nine genes on bovine chromosome (BTA) 24, all orthologous to genes on human chromosome (HSA) 18. The microsatellites have been isolated from bacterial and yeast artificial chromosome clones containing the genes. A linkage map was developed including these polymorphic markers and four anonymous, published microsatellites. Yeast artificial chromosomes containing six of these genes have also been mapped using fluorescent in situ hybridization (FISH), thereby tying the linkage map together with the physical map of BTA24. Comparing gene location on HSA18 and BTA24 identifies four regions of conserved gene order, each containing at least two genes. These genes identify six regions of conserved order between human and mouse, two more than in the human-bovine comparison. The breakpoints between regions of conserved order for human-bovine are also breakpoints in the human-mouse comparison. The centromere identifies a fifth conserved region if the BTA24 centromere is orthologous with the HSA18 centromere.
Allogeneic peripheral blood stem cell transplantation (alloPBSCT) is an emerging technology. As this technology develops, transplant centers are concerned with looking for technologic advances that will result in improvements in clinical outcomes and lower costs. We provide comparative estimates of costs and resource use for alloPBSCT in comparison to allogeneic bone marrow transplantation (alloBMT) for persons with hematologic malignancies from the time of harvest to 100 days post transplant. A retrospective, cost-identification analysis was conducted for patients in two consecutive phase II clinical trials at the University of Nebraska Medical Center. Identical preparative regimens, graft-versus-host disease prophylaxis, post-transplant hematopoietic colony-stimulating factor treatment regimens, and discharge criteria were used. Total median costs were $18,304 lower for alloPBSCT, with lower costs during recovery; specifically for hospitalization, platelet products, hematopoietic growth factors, intravenous hyperalimentation, supportive care agents, supplies, and antibacterial agents. This study provides preliminary evidence for short-term cost savings associated with alloPBSCT. However, concerns exist over the potential for higher costs due to preliminary reports of higher rates of chronic graft-versus-host disease, as well as more intensive induction regimens that may result in lower relapse rates. The premature adoption of new technologies based on short-term economic factors, in the absence of adequate clinical trial data, may prove to be ill-advised, particularly for complex medical treatments such as allogeneic transplantation.
The purpose of this paper was to (1) comprehensively analyze transplant-related costs for predicted temporal cost shifting and (2) to evaluate whether previous findings of decreasing costs of care persisted using a cost analysis of 353 NHL patients who received autologous stem cell transplantation (SCT) at the University of Nebraska Medical Center. All transplant-related costs between the patient's initial consult and program dismissal were obtained and inflated to constant 1995 dollars. Homogeneous resources were categorized into six cost-drivers and subdivided into outpatient, transplant, and additional inpatient time periods in order to evaluate resource utilization and cost shifting patterns. Between 1989 and 1991 both the average length of stay and comprehensive costs decreased 4.9 days and 14%, respectively. By 1995 additional decreases of 25.7 days and 51% led to an overall 7 year cost decline of 65%. Percent contributions of the six cost-drivers remained similar demonstrating uniformed suppression in transplant-related resource consumption. In contrast, the timing of resource utilization changed dramatically, with transplant hospitalization costs accounting for 83% of the overall costs in 1989, 71% by 1992, and only 45% in 1995, while total outpatient's contribution was 14%, 26% and 49%. Before 1991 ebbing costs were likely related to the development of new technologies such as hematopoietic growth factors and peripheral SCT, while the three-fold larger improvement in costs reported by 1995 are presumably associated with learning curve effects such as organizational changes, increased use of coordinated outpatient facilities, and the more cost-effective use of laboratory tests and pharmaceuticals.
Two case studies are used to discuss topical issues current in follow-up management of patients with early stage breast cancer. These issues include the role of screening and diagnostic bone scintigraphy and patient self-advocacy in clinical management.
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OBJECTIVE: To evaluate the pregnancy potential of frozen-thawed surgically retrieved epididymal sperm when used with intracytoplasmic sperm injection (ICSI). PATIENTS AND METHODS: From August 1994 to January 1997, 20 thawed samples of sperm from 19 patients, surgically retrieved and frozen after percutaneous or open epididymal aspiration, were used for ICSI. The results were compared with those obtained using fresh sperm obtained at the same procedure. RESULTS: Of the specimens of surgically retrieved sperm which had been frozen, stored and thawed, 15 had sufficient motile sperm for use with ICSI. The fertilization, cleavage and pregnancy rates in those cycles were similar to the same couples' previous cycle using fresh sperm from the same collection and to the overall results in the NURTURE ICSI programme obtained with fresh epididymal sperm. CONCLUSION: Scrotal exploration for diagnostic testicular biopsy and/or reconstructive surgery without having access to sperm-freezing and storage facilities could represent a lost opportunity for the patient.
Many of the complications of high-dose therapy with hematopoietic stem cells are caused by or lead to the multiple-organ dysfunction syndrome (MODS). In hematopoietic stem cell transplantation (HSCT), acquired antithrombin III (ATIII) deficiency is independently associated with MODS to the exclusion of transplant type, preparative regimen, and bacteremia. In experimental settings, replacement of ATIII can ameliorate the severity of MODS that develops in response to a variety of pathologic stimuli, suggesting that ATIII supplementation might improve the clinical course of MODS in patients undergoing HSCT. We performed a study to determine if ATIII can improve the morbidity of MODS in HSCT. Forty-nine patients undergoing HSCT, who developed pulmonary dysfunction (oxygen saturation of <90%), central nervous system dysfunction (drop of >4 points in the mini-mental status exam), or hepatic dysfunction (bilirubin >34 micromol/L [2.0 mg%], weight gain of >5% over baseline, and abdominal pain, possibly of hepatic origin) with a concomitant ATIII activity of <84% were double-blind randomized to receive ATIII concentrate, 70 units/kg within 24 hours of recognition of initial organ dysfunction followed by 50 units/kg 8, 16, 48, and 72 hours later, or albumin placebo. The group randomized to ATIII had a lower severity-of-illness score (15.7 +/- 19.2 vs. 28.6 +/- 25.2, p = 0.03), shorter duration of hospitalization (14.9 +/- 16.7 vs. 25.7 /- 17.9 days, p = 0.03), and lower hospital charges ($138,700 +/- $23,500 vs. $206,400 +/- $34,000). ATIII concentrate was associated with improved morbidity of MODS in patients undergoing HSCT when given early in the evolution of the syndrome.