Informed decision making for cancer screening--not all of the ethical issues have been considered.
Explore the source record for details and available documents.
Decision Making↗
Biomedical subjects
M Parker
Publications and source records attributed to M Parker.
Religiosity and mental health in southern, community-dwelling older adults.
This study considers potential interaction effects of three measures of religiosity, organized (OR), non-organized (NOR), and intrinsic religiosity (IR), on depression and general mental health, controlling for socio-demographic characteristics and mobility. In-home interviews were conducted among a stratified random sample of Medicare beneficiaries from five central Alabama counties (the University of Alabama at Birmingham Study of Aging). Those who were high on all three dimensions of religiosity reported having fewer symptoms of depression and better mental health than did those who were low on all three dimensions of religiosity. Subjects who scored high on OR reported lower levels of depression (F (1,981) = 3.97, p<0.05). Neither IR nor NOR had salutary effects on the measure of depression nor on the general measure of mental health.The interpretation of the relationships of religiosity with the Geriatric Depression Scale (GDS) and the general mental health (Mental Component Score of the SF-12; MCS) measures was complicated by the presence of three way interactions (F (1,981) = 9.02, p<0.01 and F (1, 981) = 5.46, p<0.05, for GDS and MCS respectively). The presence of interaction effects between the different dimensions of religiosity and mental health affirms the importance of remaining sensitive to the multidimensional nature of religiousness and its relationships with measures of mental health.
Activities of Daily Living↗
Concern for families and individuals in clinical genetics.
Clinical geneticists are increasingly confronted with ethical tensions between their responsibilities to individual patients and to other family members. This paper considers the ethical implications of a "familial" conception of the clinical genetics role. It argues that dogmatic adherence to either the familial or to the individualistic conception of clinical genetics has the potential to lead to significant harms and to fail to take important obligations seriously. Geneticists are likely to continue to be required to make moral judgments in the resolution of such tensions and may find it useful to have access to ethics training and support.
Confidentiality↗
Bone remodeling at the endocortical surface of the human femoral neck: a mechanism for regional cortical thinning in cases of hip fracture.
UNLABELLED: Endocortical remodeling and wall thickness (W.Th.) were measured in femoral neck bone from 12 female fracture cases (81.3 +/- 1.5 years) and 12 sex-matched controls (81.9 +/- 1.9 years). Regionally, osteoid and eroded surface were increased, whereas W.Th. was reduced. These processes likely contribute to cortical bone loss seen in hip fracture. INTRODUCTION: Because periosteal expression of alkaline phosphatase was similar between cases and controls, we hypothesized that the mechanism causing the marked femoral neck cortical thinning associated with hip fracture may be net endocortical bone loss. METHODS: Twelve female cases of femoral neck fracture (mean age = 81.3 +/- 1.5 years) and 12 age- and sex-matched postmortem controls (mean age = 81.9 +/- 1.9 years) were included in the study. Samples of their femoral neck bone were embedded in methyl methacrylate, sectioned at 10 microm, and stained with Solochrome cyanine R and Goldner's trichrome for the detection of osteoid (%OS/BS) and resorption surfaces (%ES/BS) respectively. In addition, wall thickness (W.Th.) and lamellar thickness (Lm.Th.) data were also collected from identifiable endocortical bone packets as a measure of formative potential. RESULTS AND CONCLUSIONS: %OS/BS was significantly elevated in the anterior (control = 3.4 +/- 0.7: fracture = 11.0 +/- 2.3; p = 0.0001), inferior (3.4 +/- 1.0: 9.9 +/- 3.0; p = 0.0009), and posterior quadrants (3.2 +/- 0.8: 9.1 +/- 2.3; p = 0.0021). Only for anterior region was increased %ES/BS demonstrated in the fracture group (2.8 +/- 0.6: 5.3 +/- 0.7; p = 0.055). W.Th. (mm) was reduced only in the inferior region of the fracture cases (control = 33.7 +/- 1.2: fracture = 30.6 +/- 0.9; p = 0.013), whereas Lm.Th. was also reduced inferiorly (control = 2.7 +/- 0.08: fracture = 2.5 +/- 0.08; p = 0.042). These data suggest that an endocortical remodeling imbalance involving reduced bone formation within inferior region coupled with elevated anterior resorption may make an important contribution to the cortical thinning observed in cases of femoral neck fracture.
Aged↗
Osteocyte density in aging subjects is enhanced in bone adjacent to remodeling haversian systems.
The osteocyte is a candidate regulatory cell for bone remodeling. Previously, we demonstrated that there is a substantial (approximately 50%) loss of osteocytes from their lacunae in the cortex of the elderly femoral neck. Higher occupancy was evident in tissue exhibiting high remodeling and high porosity. The present study examines the distribution of osteocytes within individual osteonal systems at differing stages of the remodeling cycle. In 22 subjects, lacunar density, osteocyte density, and their quotient, the percent lacunar occupancy, was assessed up to a distance of 65 microm from the canal surface in six quiescent, resorbing, and forming osteons. In both forming (p = 0.024) and resorbing (p = 0.034) osteons, osteocyte densities were significantly higher in cases of hip fracture than controls. However, there were no significant between-group differences in lacunar occupancy. In both cases and controls, osteocyte density (p < 0.0001; mean difference +/-SEM: 157 +/- 34/mm2) and lacunar occupancy (p = 0.025; mean difference: 8.1 +/- 3.4%) were shown to be significantly higher in forming compared with quiescent osteons. Interestingly, resorbing systems also exhibited significantly elevated osteocyte density in both the fracture and the control group combined (mean difference 76 +/- 23/mm2; p = 0.003). Lacunar occupancy was also greater in resorbing compared with quiescent osteons (both groups combined: p = 0.022; mean difference: 5.7 +/- 2.3%). Elevated osteocyte density and lacunar occupancy in forming compared with quiescent systems was expected because of the likely effects of aging on quiescent osteons. However, the higher levels of these parameters in resorbing compared with quiescent systems was the opposite of what we expected and suggests that, in addition to their postulated mechanosensory role in the suppression of remodeling and bone loss, osteocytes might also contribute to processes initiating or maintaining bone resorption.
Aged↗
Patterns of osteocytic endothelial nitric oxide synthase expression in the femoral neck cortex: differences between cases of intracapsular hip fracture and controls.
Evidence indicates that extensive amalgamation of adjacent resorbing osteons is responsible for destroying the microstructural integrity of the femoral neck's inferior cortex in osteoporotic hip fracture. Such osteonal amalgamation is likely to involve a failure to limit excessive resorption, but its mechanistic basis remains enigmatic. Nitric oxide (NO) inhibits osteoclastic bone destruction, and in normal bone cells its generation by endothelial nitric oxide synthase (eNOS, the predominant bone isoform) is enhanced by mechanical stimuli and estrogen, which both protect against fracture. To determine whether eNOS expression in osteocytes reflects their proposed role in regulating remodeling, we have examined patterns of osteocyte eNOS immunolabeling in the femoral neck cortex of seven cases of hip fracture and seven controls (females aged 68-96 years). The density of eNOS+ cells (mm(-2)) was 53% lower in the inferior cortex of the fracture cases (p < 0.0004), but was similar in the superior cortex. eNOS+ osteocytes were, on average, 22% further from their nearest blood supply, than osteocytes in general (p < 0.0001) and the nearest eNOS+ osteocyte was 57% further from its nearest canal surface (p < 0.0001). This differential distribution of eNOS+ osteocytes was significantly more pronounced in the cortices of fracture cases (p < 0.0001). We conclude that the normal regional and osteonal pattern of eNOS expression by osteocytes is disrupted in hip fracture, particularly at sites that are loaded most by physical activity. These results suggest that eNOS+ osteocytes may normally act as sentinels confining resorption within single osteons. A reduction in their number, coupled to an increase in their remoteness from canal surfaces, may thus permit the irreversible merging of resorbing osteons, and thus contribute to the marked increase in the fragility of osteoporotic bone.
Aged↗
Radiosensitization and DNA repair inhibition by pentoxifylline in NIH3T3 p53 transfectants.
PURPOSE: To examine the role of p53 mutations in the modulation of DNA repair and radiotoxicity by pentoxifylline. MATERIALS AND METHODS: NIH3T3 murine cells transfected with mutant p53 constructs were examined for the influence of pentoxifylline on radiotoxicity to Co(60) gamma-irradiation by colony assay. DNA repair (0-100 Gy) was measured by constant-field gel electrophoresis. Apoptosis was assessed by flow cytometry with the annexin-V-binding assay. RESULTS: In the two p53 hot-spot mutant cell lines p53-S269R and p53- + 15, the SF(10) radiotoxicity enhancement factors induced by the pentoxifylline were 8.0 and 9.7, respectively. In the p53 deletion mutant p53-DeltaA cell line, the radiotoxicity enhancement factor was 2.6. No radiosensitization was obtained in the untransfected p53 wild-type cell line U-Wt and in the transfected p53 double-wild-type p53-Wt cell line. When pentoxifylline was added after irradiation at the time of maximum G2 block expression, no radiosensitization was observed in any of the five cell lines. Constant-field gel electrophoresis analyses after 20 h of repair showed that pentoxifylline suppresses DNA double-strand break repair in all p53 mutant cell lines, as indicated by repair inhibition factors of 2.0-2.3. No repair suppression was found in the p53 wild-type cell lines. CONCLUSIONS: p53 mutations are a general requirement for radiosensitization by pentoxifylline and the level of radiosensitization depends upon the location of the p53 mutation.
3T3 Cells↗
The role of the church in developing the law.
The church and other community organisations have a legitimate role to play in influencing public policy. However, intervention by the church and other religious bodies in recent litigation in Australia and the United Kingdom raises questions about the appropriateness of such bodies being permitted to intervene directly in the court process as amici curiae. We argue that there are dangers in such bodies insinuating their doctrine under the guise of legal argument in civil proceedings, but find it difficult to enunciate a principled distinction between doctrine and legal argument. We advise that judges should exercise caution in dealing with amicus submissions.
Australia↗
Quality improvement for patients with hip fracture: experience from a multi-site audit.
PROBLEM: The first East Anglian audit of hip fracture was conducted in eight hospitals during 1992. There were significant differences between hospitals in 90-day mortality, development of pressure sores, median lengths of hospital stay, and in most other process measures. Only about half the survivors recovered their pre-fracture physical function. A marked decrease in physical function (for 31%) was associated with postoperative complications. DESIGN: A re-audit was conducted in 1997 as part of a process of continuing quality improvement. This was an interview and record based prospective audit of process and outcome of care with 3 month follow up. Seven hospitals with trauma orthopaedic departments took part in both audits. Results from the 1992 audit and indicator standards for re-audit were circulated to all orthopaedic consultants, care of the elderly consultants, and lead audit facilitators at each hospital. KEY MEASURES FOR IMPROVEMENT: Processes likely to reduce postoperative complications and improve patient outcomes at 90 days. STRATEGY FOR CHANGE: As this was a multi-site audit, the project group had no direct power to bring about changes within individual NHS hospital trusts. RESULTS: Significant increases were seen in pharmaceutical thromboembolic prophylaxis (from 45% to 81%) and early mobilisation (from 56% to 70%) between 1992 and 1997. There were reduced levels of pneumonia, wound infection, pressure sores, and fatal pulmonary embolism, but no change was recorded in 3 month functional outcomes or mortality. LESSONS LEARNT: While some hospitals had made improvements in care by 1997, others were failing to maintain their level of good practice. This highlights the need for continuous quality improvement by repeating the audit cycle in order to reach and then improve standards. Rehabilitation and long term support to improve functional outcomes are key areas for future audit and research.
Aged↗
Transmural extent of acute myocardial infarction predicts long-term improvement in contractile function.
BACKGROUND: Previous animal studies have demonstrated that the transmural extent of acute myocardial infarction defined by contrast-enhanced MRI (ceMRI) relates to early restoration of flow and future improvements in contractile function. We tested the hypothesis that ceMRI would have similar predictive value in humans. METHODS AND RESULTS: Twenty-four patients who presented with their first myocardial infarction and were successfully revascularized underwent cine and ceMRI of their heart within 7 days (scan 1) of the peak MB band of creatine kinase. Cine MRI was repeated 8 to 12 weeks later (scan 2). The transmural extent of infarction on scan 1 and wall thickening on both scans were determined using a 72-segment model. A total of 524 of 1571 segments (33%) were dysfunctional on scan 1. Improvement in segmental contractile function on scan 2 was inversely related to the transmural extent of infarction on scan 1 (P=0.001). Improvement in global contractile function, as assessed by ejection fraction and mean wall thickening score, was not predicted by peak creatine kinase-MB (P=0.66) or by total infarct size, as defined by MRI (P=0.70). The best predictor of global improvement was the extent of dysfunctional myocardium that was not infarcted or had infarction comprising <25% of left ventricular wall thickness (P<0.005 for ejection fraction, P<0.001 for mean wall thickening score). CONCLUSION: In patients with acute myocardial infarction, the transmural extent of infarction defined by ceMRI predicts improvement in contractile function.
Adult↗
Revealing false paternity: some ethical considerations.
Explore the source record for details and available documents.
Confidentiality↗
Effects of age and gender on the QT response to exercise.
Although gender differences in resting corrected QT intervals have been well documented, the effects of age and exercise on gender differences in QT have not been well characterized. Data were analyzed from 91 healthy volunteers (47 women). Forty-five young subjects (aged 20 to 39 years) and 46 older subjects (61 to 84 years) were recruited. All underwent Bruce protocol stress testing. QT offset and QT peak were measured at exercise stages and during recovery. In a heart rate (HR)-independent analysis, data were divided into HR bins of 10 beats/min. In a HR-dependent analysis, 6 models were used to approximate the QT-RR relation; the best were used to analyze age and gender effects. Women had longer QT intervals than men at a HR < 100 beats/min for QT offset and < 110 beats/min for QT peak. At faster HRs, no significant differences were found. Older subjects had slightly longer QT intervals than the younger group, with a mean difference of 2 ms for QT offset and 9 ms for QT peak. Women had increased constant and slope coefficients. The QT increase in the elderly was relatively small. Gender differences in QT disappear at faster HRs, whereas age differences are smaller but are present throughout exercise, with no significant age-gender interaction. A natural logarithmic model provides the best approximation of the QT-RR relation with exercise, is simple to implement, and should become the preferred method of QT correction.
Adult↗
Human papillomavirus type 16 E6 inactivation of p53 in normal human mammary epithelial cells promotes tamoxifen-mediated apoptosis.
Aberrant p53 expression is frequently observed in mammary epithelial cells obtained from women at high risk for developing breast cancer and is a predictor for the subsequent development of malignancy. Tamoxifen has recently been shown to reduce the incidence of noninvasive breast cancer in high-risk women, but the molecular mechanism of tamoxifen chemoprevention in mammary epithelial tissue that does not overexpress the estrogen receptor is poorly understood. We suppressed p53 expression by retroviral-mediated expression of human papillomavirus type-16 E6 protein (HPV-16 E6) in human mammary epithelial cells (HMECs) to develop an in vitro model of tamoxifen chemoprevention in the context of p53 loss. Early passage p53(-) HMEC-E6-transduced cells treated with 1.0 microM tamoxifen rapidly underwent apoptosis. In contrast, early passage p53(+) HMEC-LXSN vector controls treated with 1.0 microM tamoxifen underwent G1-G0-phase arrest but did not undergo apoptosis. p53(-) HMEC-E6 cells rapidly acquired resistance to tamoxifen-mediated apoptosis after 10 passages in culture (in the absence of tamoxifen). Both p53(+) and p53(-) HMECs exhibited a low level of estrogen receptor staining and minimal estrogen binding, characteristic of proliferating normal luminal mammary epithelial cells. Tamoxifen-mediated apoptosis in p53(-) HMEC-E6 cells was not blocked by inhibitors of transcription and protein synthesis. These data suggest that the acute loss of p53 function in HMECs by expression of HPV-16 E6 results in marked sensitivity to tamoxifen-mediated apoptosis but that resistance to apoptosis rapidly develops within 10 passages in vitro. Observations in our model system predict a critical role for the early institution of tamoxifen chemoprevention.
Apoptosis↗
Colorectal hepatic metastases: resection, local ablation, and hepatic artery infusion pump are associated with prolonged survival.
BACKGROUND: Treatment of metastatic colorectal cancer to the liver is not uniform. We describe the management of metastatic colorectal cancer of the liver at a single institution during a 10-year period. METHODS: From January 1, 1990, through December 31, 1999, 174 patients were identified from the tumor registry at the University of Alabama at Birmingham with a diagnosis of metastatic colorectal cancer to the liver. Patient, tumor, laboratory, operative, and adjuvant therapy factors were analyzed, with overall survival as the endpoint. Log-rank tests were used for univariate analysis, Cox-proportional hazards model for multivariate analysis, and Kaplan-Meier curves were used for graphical representation of survival. Significance was defined as P<.05. RESULTS: Median age was 60 years (age range, 18-92 years). Seventy-nine percent of patients had synchronous liver metastases at the time of diagnosis of the primary colorectal tumor. The primary tumor was in the colon and rectum 75% and 25% of the time, respectively. Of the 89 patients who underwent operation, 73 received definitive surgical treatment for their liver metastases. Fifty-two patients underwent lobectomy or wedge resection, 5 underwent cryotherapy, and 16 had a hepatic artery infusion pump (HAIP) inserted. Median follow-up duration of surgically treated patients was 26 months. Operative mortality was 1.3%. The 3-year actuarial survivals for patients who underwent resection, HAIP, or those with unresectable disease were 70 months, 32 months, and 3 months, respectively (P<.001). By multivariate analysis, surgical intervention, a carcinoembryonic antigen level less than 200 microg/L, or a low T stage of the primary tumor were associated with prolongation of survival. CONCLUSIONS: Surgical resection should be attempted for hepatic colorectal metastases, as this is associated with prolonged overall survival. Hepatic artery infusion pump insertion seems to prolong overall survival for those with unresectable hepatic metastases, but it is not equal to resection. Aggressive surgical management of patients with hepatic colorectal metastases is safe, may prolong overall survival, and therefore should be considered in all patients with metastases confined to the liver.
Adolescent↗
Expression of legumin and vicilin genes in pea mutants and the production of legumin in transgenic plants.
Pea seeds contain two major storage proteins, legumin and vicilin, in proportions that are genetically and environmentally determined. They are synthesized from at least 40 genes and at least 10 different genetic loci. Mutant alleles at loci involved in starch synthesis, which result in perturbations in starch accumulation, also affect the expression of legumin genes, thereby influencing the legumin: vicilin ratio within the total seed protein. Examples of such alleles include r (starch-branching enzyme) and rb (ADP-glucose pyrophosphorylase), both of which result in a reduction in legumin synthesis; double mutants (rrb) show a particularly severe reduction in the amount of legumin. The effects of such mutations are specific to legumins. The amounts of vicilin are unaffected by mutations at r or rb. One of the consequences of the production of legumin from many genes is structural heterogeneity that is believed to preclude the purification of homogeneous legumin for crystallization and 3D-structure determination. Expression of cloned legumin cDNA in E. coli can result in sequence homogeneity, but E. coli is unable to carry out the normal proteolytic processing of legumin precursors and consequently such material is different from that produced in pea seeds. This paper describes the high-level synthesis, processing and assembly of pea legumin in transgenic wheat seeds, leading to the spontaneous in vitro formation of paracrystalline arrays of legumin, which may be attributed to the fact that the legumin consists of a single type of subunit. Such material might be used as a source of single-sequence, processed and assembled pea legumin for structural investigation.
Gene Expression Regulation, Plant↗
Hip fractures in Finland and Great Britain--a comparison of patient characteristics and outcomes.
All hip fracture patients (age <50 years, pathological and subtrochanteric fractures excluded) were registered at admission to hospital and at 4 months (mortality up to 1 year) between 1989 and 1997 in Peterborough District Hospital (2083 patients) and Oulu University Hospital (1702 patients). The mean age at fracture was 80.3 years in Peterborough and 78.3 years in Oulu. Respectively, 69% and 62% of the patients had been living in their own homes, 50% and 54% had been able to walk alone unassisted. In Oulu, the patients were discharged after a mean stay of 7.1 days, most of them to health care centre hospitals (71%) and only 21% to their original place of residence. In Peterborough 81% were discharged to their original place of residence after a mean stay of 15.6 days. At 4 months, 54% were living at their own homes in Peterborough and 44% in Oulu. The overall mortality at 1 year was 27.1% in Peterborough and 24.9% in Oulu.
Aged↗
Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM.
Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder involving hearing loss, branchial defects, ear pits and renal abnormalities. Oto-facio-cervical (OFC) syndrome is clinically similar to BOR syndrome, with clinical features in addition to those of BOR syndrome. Mutations in the EYA1 gene (localised to 8q13.3) account for nearly 70% of BOR syndrome cases exhibiting at least three of the major features. Small intragenic deletions of the 3' region of the gene have also been reported in patients with BOR syndrome. We have developed a fluorescent quantitative multiplex polymerase chain reaction for three 3' exons (7, 9 and 13) of the EYA1 gene. This dosage assay, combined with microsatellite marker analysis, has identified de novo deletions of the EYA1 gene and surrounding region in two patients with complex phenotypes involving features of BOR syndrome. One patient with OFC syndrome carried a large deletion of the EYA1 gene region, confirming that OFC syndrome is allelic with BOR syndrome. Microsatellite analysis has shown that comparison of the boundaries of this large deletion with other reported rearrangements of the region reduces the critical region for Duane syndrome (an eye movement disorder) to between markers D8S553 and D8S1797, a genetic distance of approximately 1 cM.
Abnormalities, Multiple↗
Analysis of the consistency of intraurethral prostaglandin E(1) (MUSE) during at-home use.
OBJECTIVES: To determine the consistency of a successful response to intraurethral prostaglandin E(1) (MUSE), an effective treatment for a proportion of patients with erectile dysfunction, during at-home use in men who had a successful response in the office, to define the factors that correlated with the consistency of the response, and to determine whether patients continued long-term use. METHODS: The study group consisted of men with documented erectile dysfunction who had a successful response (grade 3 or 4 erection) to MUSE during an initial in-office dose. All enrollees completed a home diary assessing the treatment success during at least five medication administrations. Factors such as patient age, vascular risk factor status, and degree of in-office response were prospectively evaluated as correlates of response consistency. Finally, patient follow-up was conducted in an attempt to define how many patients were continuing to use this medication as a long-term treatment modality. RESULTS: Two hundred twelve patients underwent screening and 72 (34%) patients had in-office success. The overall per patient at-home consistency rate was 51%. None of the aforementioned factors correlated with the consistency of the response. At a mean of 9 months after beginning treatment, only 31% of the in-office responders were continuing to use MUSE. CONCLUSIONS: Although MUSE is an appropriate and safe treatment for many patients with erectile dysfunction, the lack of consistency is a significant consideration. Clinicians should pay close attention to patient education in an effort to promote realistic expectations for MUSE therapy. Furthermore, the lack of consistency may significantly lower the patient's interest in continuing this treatment long term.
Adult↗