Testing an active intervention to deter researchers' use of questionable research practices.

INTRODUCTION: In this study, we tested a simple, active "ethical consistency" intervention aimed at reducing researchers' endorsement of questionable research practices (QRPs). METHODS: We developed a simple, active ethical consistency intervention and tested it against a control using an established QRP survey instrument. Before responding to a survey that asked about attitudes towards each of fifteen QRPs, participants were randomly assigned to either a consistency or control 3-5-min writing task. A total of 201 participants completed the survey: 121 participants were recruited from a database of currently funded NSF/NIH scientists, and 80 participants were recruited from a pool of active researchers at a large university medical center in the southeastern US. Narrative responses to the writing prompts were coded and analyzed to assist post hoc interpretation of the quantitative data. RESULTS: We hypothesized that participants in the consistency condition would find ethically ambiguous QRPs less defensible and would indicate less willingness to engage in them than participants in the control condition. The results showed that the consistency intervention had no significant effect on respondents' reactions regarding the defensibility of the QRPs or their willingness to engage in them. Exploratory analyses considering the narrative themes of participants' responses indicated that participants in the control condition expressed lower perceptions of QRP defensibility and willingness. CONCLUSION: The results did not support the main hypothesis, and the consistency intervention may have had the unwanted effect of inducing increased rationalization. These results may partially explain why RCR courses often seem to have little positive effect.

Metabolic responses to fructose-1,6-diphosphate in healthy subjects.

Fructose-1,6-diphosphate (FDP) is an important naturally occurring intracellular metabolite with a direct regulatory role in many metabolic pathways. The most important and widely studied of the FDP effects has been its regulation of glycolysis, particularly the enzyme that synthesizes FDP--phosphofructokinase (PFK). Since it was observed experimentally that FDP does indeed modulate carbohydrate metabolism, we investigated whether FDP would similarly enhance carbohydrate utilization in man. The study used indirect calorimetry and was open to healthy adults (N = 45) of either sex and above legal age. After a steady metabolic state was obtained, 5 g of FDP (10%) was infused into a brachial vein. In 10 subjects, glucose (5 g) or FDP (5 g) was sequentially infused. The rapid intravenous infusion of FDP produced a slight but significant decrease in heart and respiration rates (P < .05). A significant increase in the serum concentration of inorganic phosphate (P < .0001) and the intraerythrocytic concentration of adenosine triphosphate (ATP) (P < .01) was also observed. The FDP infusion produced a decrease in plasma cholesterol and triglycerides (P < .001 and P < .01, respectively). The indirect calorimetric data indicate that the infusion produced a highly significant increase in the respiratory quotient ([RQ] P < .0001) and the energy derived from carbohydrates (P < .0001) and a significant decrease in the energy derived from lipids (P < .0001). Glucose infusion did not cause changes in any of the parameters. These data indicate that carbohydrate metabolism is stimulated by FDP.

Atrial natriuretic peptide and sodium homeostasis in compensated heart failure.

The purpose of this study was to determine whether high plasma levels of atrial natriuretic peptide (ANP) in compensated heart failure are important in the maintenance of sodium balance. This was achieved by subjecting eight dogs to bilateral atrial appendectomy (APX) to blunt the ANP response to pacing-induced heart failure. Five intact dogs served as controls. In controls, 14 days of left ventricular pacing at 240 beats/min produced a sustained fall in cardiac output and mean arterial pressure of approximately 40 and 20%, respectively; compared with cardiac output, reductions in renal blood flow (up to approximately 25%) were less pronounced and even smaller decrements in GFR occurred (up to 9%). Despite these changes and a threefold elevation in plasma norepinephrine concentration, plasma renin activity (PRA) did not increase and sodium balance was achieved during the second week of pacing in association with a six- to eightfold rise in plasma levels of ANP. Similar responses occurred in four dogs in which APX was relatively ineffective in blunting the ANP response to pacing. In marked contrast, there were substantial increments in PRA and in plasma norepinephrine concentration, and marked sodium and water retention during the last week of pacing in four dogs with APX and severely deficient ANP. These results indicate that ANP plays a critical role in promoting sodium excretion in the early stages of cardiac dysfunction.

Peripherally-placed central venous access ports: clinical and laboratory observations.

The P.A.S. Port system is a totally implantable central venous access device consisting of a miniature titanium portal and a 5.8 French catheter that is specifically designed for implantation in the forearm. The configuration of this system combined with its unique placement technology provides a simplified alternative to conventional chest-placed systems. Our group has placed a total of 61 P.A.S. Port devices in 56 patients whose ages ranged from 9 months to 85 years and who were followed for a median of 672 days. Over this period of follow-up, these devices have demonstrated a low overall complication rate (13.1%), an infection rate of 6.6%, median event-free patency of 278 days, and exceptional patient acceptance. Placement of the P.A.S. Port system is easily performed as an outpatient procedure under local anesthesia and requires neither fluoroscopy nor a conventional operating room setting. In vitro measurement of infusion pressure across a P.A.S. Port and a conventional catheter system revealed much higher resistance in the peripherally placed device, but this was found to be of no clinical significance because infusion pressures generated by flow rates up to 750 mL/hr were well within the limits of clinically available infusion pumps. We recommend the P.A.S. Port system as a safe, durable, and effective alternative for patients in whom a chest-placed device is inappropriate or undesired.

Composite dialysis access grafts.

Hemodialysis access devices constructed of expanded polytetrafluoroethylene (ePTFE) require a maturation period of seven to 14 days before cannulation. Percutaneously placed dual-lumen catheters can be used for temporary access during this interval but are associated with significant short and long term complications. Access devices constructed of Plasma-TFE (pl-TFE) (Atrium, Hollis) conduits have been reported to tolerate cannulation immediately after placement, but long term patency is inferior to that of conventional ePTFE. To combine the immediate access advantages of pl-TFE and the long term patency of ePTFE, composite grafts were constructed, which consisted of 10 to 12 centimeters of pl-TFE and the remainder of ePTFE. The pl-TFE segment was made available for immediate access and the ePTFE segment after an appropriate maturation period. Thirty percent of composite grafts were cannulated on the day of placement and 83.8 percent were cannulated within 72 hours. No complications of early access of the pl-TFE segment occurred. These grafts were compared with a cohort of conventional ePTFE grafts for the occurrence of thrombosis, infection and pseudoaneurysm. No significant differences were noted. Event-free patency of the two groups was equal (327.7 versus 346.3 days, p = 0.282). Patency after an initial thrombotic episode was slightly better in the composite group. We conclude that composite dialysis access grafts can be cannulated immediately after placement and demonstrate long term performance at least equal to that of conventional ePTFE grafts. Use of the composite graft concept should be considered when immediate dialysis is needed and to avoid the use of temporary access catheters.

Role of pressure natriuresis in long-term control of renal electrolyte excretion.

If pressure natriuresis is to play an important role in arterial pressure control, renal perfusion pressure must have a long-term effect on urinary sodium excretion. The aim of this study was to quantitate the importance of renal perfusion pressure per se in controlling renal hemodynamics and electrolyte excretion chronically. Female mongrel dogs (n = 6) were instrumented with bilateral renal artery catheters for measurement of renal perfusion pressure and occluders on both renal arteries for servo-control of renal perfusion pressure at different levels; the urinary bladder was split for determination of renal clearances and electrolyte excretion from each kidney separately. Because both kidneys were exposed to the same neurohumoral influences, any changes in renal function could be attributed to differences in renal perfusion pressure between the two kidneys. After 5 days of control, renal perfusion pressure to one kidney was reduced from 86.7 +/- 0.2 to 74.2 +/- 0.6 mm Hg for 12 days, and pressure in the contralateral kidney increased to 91.5 +/- 0.4 mm Hg. Sodium excretion decreased from 41 +/- 2 to 25 +/- 1 mmol/d in the servo-controlled kidney and increased from 41 +/- 1 to 55 +/- 1 mmol/d in the contralateral kidney during 12 days of servo-control. Urine volume, chloride excretion, and potassium excretion exhibited similar patterns during servo-control. In addition, autoregulation of effective renal plasma flow and glomerular filtration rate was relatively well maintained; however, in the low-pressure kidney, glomerular filtration rate was slightly but significantly lower (approximately 8%) than in the contralateral kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Changing clinical picture of mammary hamartoma.

During a 6-year period, we identified 12 patients (age range: 16 to 72 years) with a histologic or mammographic diagnosis of mammary hamartoma. The lesion was found in 9 of 441 open breast biopsy specimens (2%) and was identified radiographically in 5 of 8,122 mammographic examinations (less than 1%). Two groups of patients were identified. Three patients under 30 years of age underwent the excision of small palpable lesions found on pathologic examination to be mammary hamartomas (group I). In nine patients over age 30, masses were identified or confirmed on mammography (group II). Five lesions showed the classic mammographic appearance of a mammary hamartoma (a circumscribed tumor of mixed soft tissue and fatty density), and the other four were indeterminate. Presentation in these older women who had a relatively high incidence of atypical mammographic findings mandates that biopsy be performed.

Outpatient vascular access surgery: impact of a dialysis unit-based surgical facility.

The present report describes a novel approach to vascular access surgery based on the philosophy that a readily available operating room, staffed by nurses familiar with the unique problems of dialysis patients and their therapy, would reduce dialysis delays and maintain the quality of surgical care. Based on a 28-month experience with more than 1,000 access cases, we conclude that a traditional surgical setting is not necessary for either quality access graft placement or the management of access complications.

Choice of anesthetic technique for needle localized breast biopsy.

General anesthesia has been recommended to increase the accuracy and safety of needle localized biopsy (NLB). The authors' NLB experience was reviewed to determine whether the method of anesthesia affected accuracy, yield, complication rate, or cost. All biopsies were performed in a standard operating room using either local anesthesia (Group 1, n = 14), local anesthesia with an anesthesiologist present (Group 2, n = 14), or general anesthesia (Group 3, n = 10). The mean operative times were 54, 59, and 56 minutes for Groups 1, 2, and 3, respectively. In groups 1 and 2, 100 per cent of the specimen radiographs showed the target lesion had been excised, although one biopsy was indeterminate. Among Group 3 two target lesions could not be identified on specimen radiographs and one was indeterminate. There was one malignancy in Group 1 compared with four malignancies in Group 2 and two in Group 3. The average hospital bill was $1,172 for Group 1, $1,418 for Group 2, and $1,488 for Group 3. Anesthesiologists' fees added an additional $224 to Groups 2 and 3. NLB can be performed using local anesthesia without sacrificing accuracy or yield, increasing operative time, or increasing complication rate; the cost is significantly less than with general anesthesia.

A prospective randomized evaluation of chronic peritoneal catheters. Insertion site and intraperitoneal segment.

The insertion site (midline or through the lateral rectus muscle) and type of chronic dialysis catheter (straight or spiral intraperitoneal segment) were evaluated in a prospective randomized trial. Dialysis catheter complications and catheter survival were the endpoints of evaluation. Eighty-five first catheters were evaluated. Neither race, gender, renal diagnosis, type of catheter, nor insertion site was a determinant of dialysis catheter survival. Overall median catheter survival was 308 days. There were 40 catheter complications (70%, n = 28) that occurred during the first 61 days following insertion. Median time to the first complication occurring within the first 61 days was 3 days. Late catheter removals were due to peritonitis episodes that failed to resolve. Complications are frequent with peritoneal dialysis catheters, and care of the peritoneal dialysis catheters requires constant vigilance.

Mirizzi's syndrome. An uncommon cause of biliary obstruction.

An uncommon cystic-duct anomaly characterized by a course parallel to the common hepatic duct or contained in a sheath with the common hepatic duct over a significant distance can allow cystic-duct stones to occlude the common hepatic duct by extrinsic pressure. This condition is appropriately referred to as Mirizzi's syndrome. One such case is described in the present study. Recognition of this and other biliary anomalies is critical to safe operative management of calculous biliary disease.

Attenuation of ischemic renal injury with fructose 1,6-diphosphate.

Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.

The synergistic effect of total-lymphoid irradiation with extracted donor alloantigen in inducing transplantation unresponsiveness.

The synergistic effect of total lymphoid irradiation with KCl-extracted donor type antigen (H-Ag) was examined in the rat cardiac graft model. TLI therapy alone of 10, 16, and 20 Gy achieved by a 2 Gy daily treatment of WFu recipients produced modest prolongation of BUF heart survival to median survival times (MST) of 11, 26, and 30 days, respectively, in comparison with normal control (MST = 6). The TLI immunosuppressive effect was significantly potentiated with donor H-Ag when combined with 16 (greater than 100 days) but not with 10 or 20 Gy TLI therapy. This effect was specific: 16 Gy TLI treated recipients of BUF hearts rejected their grafts in a MST of 27 days when treated with third-party BN H-Ag. The state of unresponsiveness was transferable to 6 Gy total-body-irradiated WFu recipients of BUF hearts with 60 x 10(6) purified T cells isolated from TLI/H-Ag-treated rats (greater than 100) but not from normal controls (MST = 6). In vitro analysis of nontransplanted WFu rats 1-4 weeks after completion of 16 Gy TLI therapy alone demonstrated a nonspecifically reduced MLR proliferative response as well as the presence of potent nonspecific suppressor cells (NSC). By 3 or even 6 months post-TLI, W3/25- NSC displayed persistent suppressive activity and inhibited normal proliferative response to alloantigens. Limiting dilution assay revealed that the frequency of T cytotoxic cells (fTc) was severely decreased to 1:63111 at one day and to 1:16488 at one week postirradiation in comparison with normal control (1:2551). At 3 and 6 months the fTc of 1:2301 and 1:2040, respectively, approximated normal levels. These combined in vivo and in vitro results demonstrate that 16 Gy TLI therapy induces an unresponsiveness mediated by NSC and that the administration of donor type H-Ag facilitates the generation of potent regulatory T cells capable of inducing prolonged heart allograft survival.

Prolongation of heterotopic heart allograft survival by local delivery of continuous low-dose cyclosporine therapy.

The effectiveness of local versus systemic low-dose CsA (2 mg/kg/day) therapy delivered by osmotic pump for a 14-day continuous infusion was examined in the rat model. Systemic subtherapeutic CsA treatment of WFu recipients either by oral gavage or intravenously using an osmotic pump resulted in quick rejection of BUF heart allografts within a median survival time (MST) of 8 days in comparison with untreated controls (MST = 7 days). In contrast, direct local subtherapeutic CsA delivery to BUF heart allografts produced significantly (P less than 0.01) prolonged heart allograft survivals up to MST of 40 days. Splenic T cells, isolated on days 10 to 12 from locally immunosuppressed WFu recipients, revealed a nonspecifically reduced proliferative response toward alloantigens. Coculture experiments demonstrate that these T cells have the capacity to inhibit normal T cell proliferative responses in a nonspecific fashion either by their suppressor function or more likely by carrying CsA to the culture plate. In contrast, T cells isolated from WFu recipients three weeks after transplantation and tested in vitro demonstrated the presence in alloantigen specific T suppressor cells that coincided with a decreased frequency of alloantigen-specific T cytotoxic cells and may explain the extended heart allograft survival beyond the time of CsA delivery. CsA therapy delivered directly to the graft resulted in high CsA levels within the heart graft (1108 ng/0.1 g) but subtherapeutic levels in other tissues. These results demonstrate that local drug delivery is effective in inhibiting the rejection process within the graft itself, as manifested by prolonged heart allograft survival. Further, subtherapeutic CsA therapy facilitates development of Ts cells that may be responsible for the survival of heart allografts beyond the CsA delivery time.

Ability of 3M KC1-extracted histocompatibility antigen to potentiate the immunosuppressive effect of cyclosporine to prolong the survival of heterotopic rat cardiac allografts.

A soluble histocompatibility antigen preparation (HAg) derived by 3M KCl extraction of donor spleen cells has been shown to prolong rat renal allografts in CsA-treated hosts. In the present study, the effect of combined soluble antigen-CsA treatment on cardiac allograft survival was studied in WFu hosts grafted with BUF hearts. Cardiac allograft survival was prolonged in WFu recipients treated with both BUF HAg and CsA compared with survival time in untreated controls or controls treated with HAg or CsA alone. In addition, experiments were performed to test the antigenicity of the HAg extract. BUF extract given sc to WFu hosts before grafting specifically sensitized the hosts to BUF grafts, as shown by the accelerated rejection of BUF grafts but not third-party grafts. Assays to determine the major histocompatibility antigenic determinants present in the extract showed that class I and class II determinants were present.