Intuitions, principles and consequences

Some approaches to the assessment of moral intuitions are discussed. The controlled ethical trial isolates a moral issue from confounding factors and thereby clarifies what a person's intuition actually is. Casuistic reasoning from situations, where intuitions are clear, suggests or modifies principles, which can then help to make decisions in situations where intuitions are unclear. When intuitions are defended by a supporting principle, that principle can be tested by finding extreme cases, in which it is counterintuitive to follow the principle. An approach to the resolution of conflict between valid moral principles, specifically the utilitarian and justice principles, is considered. It is argued that even those who justify intuitions by a priori principles are often obliged to modify or support their principles by resort to the consideration of consequences.     

The use of monetary incentives in a community survey: impact on response rates, data quality, and cost

OBJECTIVES: To assess the effect of incentive size on response rates, data quality, and cost in a digestive health status mail survey of a community sample of health plan enrollees. DATA SOURCES/SETTING: The study population was selected from a database of enrollees in various health plans obligated to receive care at Park Nicollet Clinic-HealthSystem Minnesota, a large, multispecialty group in Minneapolis, Minnesota, and the nearby suburbs. STUDY DESIGN: A total of 1,800 HealthSystem Minnesota enrollees were randomly assigned to receive a survey with an incentive of $5 or $2. The response rates for each incentive level were determined. Data quality, as indicated by item nonresponse and scale scores, was measured. Total cost and cost per completed survey were calculated. PRINCIPAL FINDINGS: The response rate among enrollees receiving $5 (74.3 percent) was significantly higher than among those receiving $2 (67.4 percent); differences were more pronounced in the first wave of data collection. Data quality did not differ between the two incentive groups. The total cost per completed survey was higher in the $5 condition than in the $2 condition. CONCLUSIONS: A $5 incentive resulted in a higher response rate among a community patient sample with one mailing than did a $2 incentive. However, the response rates in the $2 condition approached the level of the $5 incentive, and costs were significantly lower when the full follow-up protocol was completed. Response rates were marginally increased by follow-up phone calls. The incentive level did not influence data quality. The results suggest if a survey budget is limited and a timeline is not critical, a $2 incentive provides an affordable means of increasing participation.     

Three cases of small bowel intussusception in relation to a rare lesion: inflammatory fibrous polyps

BACKGROUND/AIMS: Inflammatory fibrous polyps (IFPs), also known as inflammatory pseudotumors, occur rarely in the gastrointestinal tract. IFPs have variable presentations, often presenting as small bowel obstruction due to intussusception or, less commonly, as an incidental finding on radiological examinations or screening colonoscopies. The diagnosis and management of IFPs will be discussed through a review of the literature and a series of cases from our own institution. METHODS: A retrospective analysis of the diagnosis, management and complications of IFPs was performed by a literature review. This was accompanied by a series of 3 cases of IFPs, 2 of which causing intussusception, diagnosed and treated in our own institution. CONCLUSIONS: IFP is a rare disease and has a variable presentation, from asymptomatic to small bowel obstruction due to intussusception. IFPs cannot be differentiated from malignancy without histological examination. Therefore, whether diagnosed incidentally or in the setting of intussusception, the treatment of IFPs is surgical resection of the involved bowel.     

Prevalence of positive preoperative pregnancy testing in teenagers scheduled for orthopedic surgery

The pregnancy status of female teenagers presenting for orthopaedic surgery is often unknown. Anesthetics may have teratogenic or abortive effects. The authors report the results of a screening program for unrecognized pregnancy in 532 female teenagers presenting for orthopaedic surgery. Five patients with a positive urine human chorionic gonadotropin test were identified, for a prevalence of 1 positive result in 106 patients tested (0.9%). Surgery was cancelled in each case.     

Acute and chronic physiological effects of silver exposure in three marine teleosts

This study evaluated the physiological effects of waterborne silver (added as AgNO(3)) on seawater fish, using acute (48-72 h) high level exposures (250-650 microg/l Ag) on tidepool sculpins (Oligocottus maculosus), and chronic (up to 21 day) low level exposures (1.5-50 microg/l Ag) on tidepool sculpins, plainfin midshipmen (Porichthys notatus), and rainbow trout (Oncorhynchus mykiss). Sculpins were tested at different salinities. Acclimation to lower salinity (18 vs 30 ppt) led to altered physiology, with higher ammonia excretion (J(Amm)), lower oxygen consumption, and lower branchial and intestinal Na(+)/K(+)-ATPase activities, but no difference in drinking rate. Short-term exposure to high silver levels tended to stimulate M(O(2)), J(Amm), and drinking rate. However, long-term exposure to low levels of silver depressed both J(Amm) and M(O(2)), and also led to decreased drinking rates. Both inhibition and stimulation of Na(+)/K(+)-ATPase activity occurred, dependent upon length and concentration of exposure, salinity (18 vs 30 ppt), tissue (gill vs intestine), and fish species (sculpin vs midshipmen vs rainbow trout). While the effects were variable, due to differing balances between inhibitory and compensatory responses, chronic silver exposure significantly altered Na(+)/K(+)-ATPase activity levels in almost all tests. In total, these findings reinforce the view that intestinal osmoregulatory function (drinking, Na(+)/K(+)-ATPase activity) is an important site of toxic impact for waterborne silver, that gill Na(+)/K(+)-ATPase activity is also a site of impact, and that chronic exposures at silver concentrations (1.5, 14.5 microg/l Ag) close to current or proposed water quality guidelines (albeit much higher than normal environmental levels), exert a variety of sublethal effects on marine teleosts.     

Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients

The relationship between the dose of tacrolimus, trough tacrolimus blood concentration, and selected clinical endpoints (acute rejection, nephrotoxicity, and other toxicities) were examined in a prospective, multicenter clinical trial to validate the use of an enzyme-linked immunosorbent assay (ELISA) for monitoring whole-blood concentrations of tacrolimus in liver transplant patients. A total of 111 subjects from six transplant centers were evaluated over 12 weeks posttransplantation. In addition to trough tacrolimus blood concentrations, hematocrit, ALT, AST, GGTP, alkaline phosphatase, total bilirubin, serum creatinine, BUN, serum potassium, serum magnesium, blood glucose, and serum albumin were also measured. The relationship between trough tacrolimus blood concentrations and clinical endpoints was analyzed using both a logistic regression model and a Cox proportional hazard model. By logistic regression analysis, a statistically significant (p = 0.0465) relationship between increasing trough tacrolimus blood concentrations and decreasing risk of acute rejection was demonstrated over a 7-day time window. Nephrotoxicity and other toxicities also demonstrated statistically significant relationships with trough tacrolimus blood concentrations. The results of the Cox analysis were consistent with the logistic regression analysis. Using receiver operator characteristic curves, trough tacrolimus concentrations as measured by the ELISA method were able to differentiate the occurrence of nephrotoxicity and toxicity from nonevents. To minimize nephrotoxicity of tacrolimus, it is necessary to maintain trough blood concentrations below 15 ng/ml. This study demonstrates that the ELISA method used to measure tacrolimus blood concentrations in this study provides information of predictive value for managing the risk of nephrotoxicity, other toxicity, and rejection in liver transplant patients.     

Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells

We identify a novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival. Suppression of VEGF expression in metastatic cells in vitro induced their apoptosis, in addition to inhibiting the constitutively elevated phosphatidylinositol 3'-kinase activity that is characteristic of these cells and important for their survival. Hypoxia enhanced the survival of metastatic cells by increasing VEGF expression. The importance of the VEGF receptor neuropilin was indicated by the ability of a neuropilin-binding VEGF isoform to enhance breast carcinoma survival. Moreover, the expression of neuropilin in neuropilin-deficient breast carcinoma cells protected them from apoptosis. The identification of this VEGF autocrine signaling pathway has important implications for tumor metastasis and therapeutic intervention.     

Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas

Gemcitabine has been shown to be an active agent in the treatment of pancreatic cancer. This study was conducted to prospectively examine the tolerance and early efficacy of adjuvant gemcitabine following radiotherapy with concurrent 5-fluorouracil (5-FU) for nonmetastatic pancreatic adenocarcinoma. Twenty-three patients, median age 64 years, were treated with combined modality therapy. Nine patients underwent tumor resection before chemoradiation; 14 patients with locally unresectable tumors received definitive chemoradiation. Radiotherapy utilized four fields to the tumor and lymphatics to 45 Gy, plus a lateral boost to 50.4 Gy. Concurrent 5-FU 500 mg/m(2)/day was administered on days 1-3 and 29-31, followed by 4 months of gemcitabine 1,000 mg/m(2)/week for 3 weeks (fourth week break). Adjuvant gemcitabine was well tolerated. Eighty-three percent of the patients completed three to four cycles. The primary dose-limiting toxicity was leukopenia, which was observed in 10 patients (43%). Nonhematologic toxicities were reported in five patients (22%). There were no cases of gemcitabine-induced radiation recall and there have been no deaths attributed to treatment toxicity. Median follow-up for the 23 patients was 12 months (range, 5-50); the actuarial median survival was 13 months. This report confirms that adjuvant gemcitabine following radiotherapy with concurrent 5-FU for nonmetastatic pancreatic adenocarcinoma can be safely administered.     

Glutamine synthetase activity and expression are not affected by the development of motor neuronopathy in the G93A SOD-1/ALS mouse

ApoI/Fas belongs to the tumor necrosis factor receptor (TNFR) superfamily and mediates cell death in various cell types. Earlier studies from this laboratory have shown that Fas-mediated cell death of glioma cells occur, in part, through the production of reactive oxygen species (ROS). To further dissect the molecular mechanisms that are involved in Fas-induced cell death, we compared gene expression between Fas-treated and saline-treated human neuroglioma H4 cells by using the technique of mRNA differential display. This approach led to the identification of hSCO1, a component of the inner mitochondrial membrane, which is required for the correct assembly, and catalytic function of cytochrome-c oxidase, as a Fas down-regulated gene. The decrease in hSCO1 mRNA expression was time-dependent, becoming most prominent after 4 h of Fas-treatment. Morphological changes observed by confocal microscopy revealed that after 4 h of Fas-treatment, the cells undergo membrane blebbing and early formation of apoptotic bodies. These observations are discussed in terms of their support for an important role of mitochondrial events in Fas-induced apoptosis.