Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma.

PURPOSE: In the West, curative (R0) resection is achieved in approximately 50% of patients with localized gastric carcinoma, and more than 60% die of cancer following an R0 resection. A multi-institutional study of preoperative chemoradiotherapy was done to assess the R0 resection rate, pathologic complete response (pathCR) rate, safety, and survival in patients with resectable gastric carcinoma. PATIENTS AND METHODS: Operable patients with localized gastric adenocarcinoma were eligible. Staging also included a laparoscopy and endoscopic ultrasonography (EUS). Patients received up to two 28-day cycles of induction chemotherapy of fluorouracil, leucovorin, and cisplatin, followed by 45 Gy of radiation plus concurrent fluorouracil. Patients were then staged and surgery was attempted. RESULTS: Thirty-four patients were registered at three institutions. One ineligible patient was excluded. Most patients had a promixal cancer and EUST3N1 designation. Twenty-eight (85%) of 33 patients underwent surgery. The R0 resection rate was 70% and pathCR rate was 30%. A pathologic partial response (< 10% residual carcinoma in the primary) occurred in eight patients (24%). EUS T plus N and postsurgery T plus N correlation showed significant downstaging (P = <.01). The median survival time for 33 patients was 33.7 months. Patients achieving a pathCR or pathPR had a significantly longer median survival time (63.9 months) than those achieving less than pathPR (12.6 months; P =.03). There were two treatment-related deaths. CONCLUSION: Our data suggest that the three-step strategy of preoperative induction chemotherapy followed by chemoradiotherapy resulted in substantial pathologic response that resulted in durable survival time. This strategy is worthy of a direct comparison with postoperative adjuvant chemoradiotherapy.

Economic cost of expanded criteria donors in cadaveric renal transplantation: analysis of Medicare payments.

BACKGROUND: The use of expanded criteria donors (ECDs) in cadaveric renal transplantation is increasing in the US. We assess the economic impact of the use of ECDs to the Medicare end stage renal disease program. METHODS: The United Nations for Organ Sharing renal transplant registry was merged to Medicare claims data for 42,868 cadaveric renal transplants performed between 1991-1996 using USRDS identifiers. Only recipients for whom Medicare was the primary payer were considered, leaving 34,534 transplants. An ECD was defined as (1) age < or =5 or > or =55 years, (2) nonheart-beating donors, donor history of (3) hypertension or (4) diabetes. High-risk recipients (HRR) were age >60 years, or a retransplant. Medicare payments from the pretransplant dialysis period were projected forward to provide a financial "breakeven point" with transplantation. RESULTS: There were 25,600 non-HRR transplants, with 5,718 (22%) using ECDs, and 8,934 HRR transplants, of which 2,200 (25%) used ECDs. The 5-year present value of payments for non-ECD/non-HRR donor/recipient pairings was $121,698 vs. $143,329 for ECD/non-HRR pairings (P<0.0001) and, similarly was $134,185 for non-ECD/HRR pairings vs. $165,716 for ECD/HRR pairings (P<0.0001). The break even point with hemodialysis ranged from 4.4 years for non-ECD/ non-HRR pairings to 13 years for the ECD/HRR combinations but was sensitive to small changes in graft survival. Transplantation was always less expensive than hemodialysis in the long run. CONCLUSIONS: The impact of ECDs on Medicare payments is most pronounced in high-risk recipients. Cadaveric renal transplantation is a cost-saving treatment strategy for the Medicare ESRD program regardless of recipient risk status or the use of ECDs.

The economic benefit of allocation of kidneys based on cross-reactive group matching.

BACKGROUND: Recently the United Network for Organ Sharing (UNOS) began a pilot study to evaluate prospectively the merits of an allocation of cadaveric kidneys based on broader classes of HLA antigens, called cross-reactive groups (CREG). The objectives of the pilot study consider patient outcomes, but not the potential economic impact of a CREG-based allocation. This study predicts the impact of a CREG-based local allocation of cadaveric kidneys on 3-year Medicare payments and graft survival. METHODS: The UNOS renal transplant registry was merged to Medicare claims data for 1991-1997 by the United States Renal Data System. Average accumulated Medicare payments and graft survival up to 3 years posttransplant for first cadaveric renal transplant recipients were stratified by cross-reactive group mismatch categories. The economic impact was defined as the difference in average 3-year costs per transplant between the current and proposed allocation algorithms. Average 3-year costs were computed as a weighted average of costs, where the weights were the actual and predicted distributions of transplants across cross-reactive group categories. RESULTS: Results suggest that an organ allocation based on cross-reactive group matching criteria would result in a 3-year cost savings of $1,231 (2%) per transplant, and an average 3-year graft survival improvement of 0.6%. CONCLUSIONS: Cost savings and graft survival improvements can be expected if CREG criteria were to replace current criteria in the current allocation policy for cadaveric kidneys, although the savings appear to be smaller than may be achievable through expanded HLA matching.

Cadaveric versus living donor kidney transplantation: a Medicare payment analysis.

BACKGROUND: We found previously that the clinical advantages of living donor (LD) renal transplantation lead to financial cost savings compared to either cadaveric donation (CAD) or dialysis. Here, we analyze the sources of the cost savings of LD versus CAD kidney transplantation. METHODS: We used United States Renal Data System data to merge United Network for Organ Sharing registry information with Medicare claims data for 1991-1996. Information was available for 42,868 CAD and 13,754 LD transplants. More than 5 million Medicare payment records were analyzed. We calculated the difference in average payments made by Medicare for CAD and LD for services provided during the first posttransplant year. RESULTS: Average total payments were $39,534 and $24,652 for CAD and LD, respectively (P<0.0001) during the first posttransplant year. The largest source of the difference in payments was in inpatient hospitals, representing $10,653.67 (P<0.0001). For patients who had Medicare as the primary payer, average transplant charges were significantly higher for CAD donation ($79,730 vs. $69,547, P<0.0001); average transplant payments demonstrated no statistical differences ($28,483 vs. $28,447, P = 0.858). Therefore, inferred profitability was significantly higher for LD. CONCLUSIONS: Medicare payments are remarkably lower for LD compared to CAD in every category. The single largest cost saving comes from inpatient hospital services. A portion of the savings from LD could be invested in programs to expand living kidney donation.

The economic implications of HLA matching in cadaveric renal transplantation.

BACKGROUND: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria is controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. METHODS: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. RESULTS: Average Medicare payments for renal transplant recipients in the three years after transplantation increased from 60,436 dollars per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to 80,807 dollars for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P<0.001). By three years after transplantation, the average Medicare payments were 64,119 dollars for transplantations of kidneys with less than 12 hours of cold ischemia time and 74,997 dollars for those with more than 36 hours (P<0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings (4,290 dollars per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold ischemia time were considered. CONCLUSIONS: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold ischemia time were greater than the advantages of optimizing HLA matching.

Partially formed native tertiary interactions in the A-state of cytochrome c.

Considerable insight into protein structure, stability, and folding has been obtained from studies of non-native states. We have studied the extent of native tertiary contacts in one such molecule, the A-state of yeast iso-1-ferricytochrome c. Previously, we showed that the interface between the N and C-terminal helices is completely formed in the A-state. Here, we focus on interactions essential for forming the heme pocket of eukaryotic cytochromes c. To determine the extent of these interactions, we used saturation mutagenesis at the evolutionarily invariant residue leucine 68, and measured the free energy of denaturation for the native states and the A-states of functional variants. We show that, unlike the interaction between the terminal helices, the native interactions between the 60s helix and the rest of the protein are not completely formed in the A-state.

Role of configurational gating in intracomplex electron transfer from cytochrome c to the radical cation in cytochrome c peroxidase.

Electron transfer within complexes of cytochrome c (Cc) and cytochrome c peroxidase (CcP) was studied to determine whether the reactions are gated by fluctuations in configuration. Electron transfer in the physiological complex of yeast Cc (yCc) and CcP was studied using the Ru-39-Cc derivative, in which the H39C/C102T variant of yeast iso-1-cytochrome c is labeled at the single cysteine residue on the back surface with trisbipyridylruthenium(II). Laser excitation of the 1:1 Ru-39-Cc-CcP compound I complex at low ionic strength results in rapid electron transfer from RuII to heme c FeIII, followed by electron transfer from heme c FeII to the Trp-191 indolyl radical cation with a rate constant keta of 2 x 10(6) s-1 at 20 degrees C. keta is not changed by increasing the viscosity up to 40 cP with glycerol and is independent of temperature. These results suggest that this reaction is not gated by fluctuations in the configuration of the complex, but may represent the elementary electron transfer step. The value of keta is consistent with the efficient pathway for electron transfer in the crystalline yCc-CcP complex, which has a distance of 16 A between the edge of heme c and the Trp-191 indole [Pelletier, H., and Kraut, J. (1992) Science 258, 1748-1755]. Electron transfer in the complex of horse Cc (hCc) and CcP was examined using Ru-27-Cc, in which hCc is labeled with trisbipyridylruthenium(II) at Lys-27. Laser excitation of the Ru-27-Cc-CcP complex results in electron transfer from RuII to heme c FeII with a rate constant k1 of 2.3 x 10(7) s-1, followed by oxidation of the Trp-191 indole to a radical cation by RuIII with a rate constant k3 of 7 x 10(6) s-1. The cycle is completed by electron transfer from heme c FeII to the Trp-191 radical cation with a rate constant k4 of 6.1 x 10(4) s-1. The rate constant k4 decreases to 3.4 x 10(3) s-1 as the viscosity is increased to 84 cP, but the rate constants k1 and k3 remain the same. The results are consistent with a gating mechanism in which the Ru-27-Cc-CcP complex undergoes fluctuations between a major state A with the configuration of the hCc-CcP crystalline complex and a minor state B with the configuration of the yCc-CcP complex. The hCc-CcP complex, state A, has an inefficient pathway for electron transfer from heme c to the Trp-191 indolyl radical cation with a distance of 20.5 A and a predicted value of 5 x 10(2) s-1 for k4A. The observed rate constant k4 is thus gated by the rate constant ka for conversion of state A to state B, where the rate of electron transfer k4B is expected to be 2 x 10(6) s-1. The temperature dependence of k4 provides activation parameters that are consistent with the proposed gating mechanism. These studies provide evidence that configurational gating does not control electron transfer in the physiological yCc-CcP complex, but is required in the nonphysiological hCc-CcP complex.

The complexities of DNA computation.

Over the past few years, a handful of insightful researchers have bridged the gap between biological computing theory and actual DNA-based computation. By using ingenious encoding techniques and clever molecular-biological manipulations, simple versions of computationally complex problems have been experimentally approached or resolved. However, the technical problems revealed during the execution of these scientific set pieces make it unlikely that DNA will ever rival silicon for the solution of any real-world problem.

Relationship between clinical competence and interpersonal and communication skills in standardized-patient assessment.

PURPOSE: To evaluate the relationship between clinical competence and interpersonal and communication skills, in an attempt to clarify current thinking about these two dimensions as measured with standardized-patient (SP) examinations. METHOD: Simple Pearson correlations were computed between total examination scores for clinical competence and interpersonal and communication skills. Three sets of different types of data involving 15 separate examinations were used to explore the generality of the findings. To control for a within-case halo effect and measurement error, corrected cross-half correlations and corrected cross-case correlations were also computed. RESULTS: The simple correlations and the corrected cross-half and cross-case correlations showed moderate and above relationships between these two dimensions in the clinical context. The simple correlations centered around .50, and the corrected cross-half and cross-case correlations were slightly higher, centering around .65 and .70, respectively. CONCLUSION: The authors' thinking is that the moderate relationship between clinical competence and interpersonal and communication skills is not due to a flaw in the measurement of clinical competence, as has been suggested, but rather is a natural consequence of the clinical encounter, which exacts an interdependence of these two dimensions. At least, this possibility must be seriously considered so medical educators can think and act appropriately in the assessment of clinical performance.

Transport effects on surface-volume biological reactions.

Many cellular reactions involve a reactant in solution binding to or dissociating from a reactant confined to a surface. This is true as well for a BIAcore, an optical biosensor that is widely used to study the interaction of biomolecules. In the flow cell of this instrument, one of the reactants is immobilized on a flat sensor surface while the other reactant flows past the surface. Both diffusion and convection play important roles in bringing the reactants into contact. Usually BIAcore binding data are analyzed using well known expressions that are valid only in the reaction-limited case when the Damköhler number Da is small. Asymptotic and singular perturbation techniques are used to analyze dissociation of the bound state when Da is small and O(1). Linear and nonlinear integral equations result from the analysis; explicit and asymptotic solutions are constructed for physically realizable cases. In addition, effective rate constants are derived that illustrate the effects of transport on the measured rate constants. All these expressions provide a direct way to estimate the rate constants from BIAcore binding data.

Protective effects of CGS 30440, a combined angiotensin-converting enzyme inhibitor and neutral endopeptidase inhibitor, in a model of chronic renal failure.

The purpose of these studies was to compare the effects of CGS 30440 (CGS), a dual angiotensin-converting enzyme inhibitor (ACEI)/neutral endopeptidase inhibitor (NEPI) to benazepril (BZ), an ACEI, in a model of five-sixths nephrectomy. The doses of BZ and CGS 30440 tested were 6.5 micromol/kg/day and 2.2 micromol/kg/day. Drugs or vehicle (V) were administered subcutaneously for 6 weeks with dosing initiated 1 week after renal mass reduction. At 6 weeks of receiving drug (7 weeks after five-sixths nephrectomy), CGS/6.5 and BZ/6.5 and CGS/2.2 maintained systolic blood pressures (SBP) at presurgical values. BZ/2.2 did not reduce SBP and was similar to the V group. Urinary protein excretion increased >10-fold in the V-treated group. BZ, at either dose, reduced the proteinuria slightly. CGS/6.5 and CGS/2.2 caused significant (p < 0.05) reductions in proteinuria. Creatinine clearance (Cr(cl)), was reduced by 82% in V, 65 and 61% in the CGS/6.5 and CGS/2.2 groups, and by 69 and 74% in the BZ/6.5 and BZ/2.2 groups, respectively. Both CGS treatments improved the fractional excretion of Na+ (%FE(Na)) significantly from the BZ and V groups. The %FE(Na) for BZ at either dose did not differ from that of V. Elevated urinary cyclic guanosine monophosphate (cGMP), an indicator suggesting increased intrarenal levels of atrial natriuretic peptide (ANP), was observed only in the CGS groups. Histologic examination indicated that BZ/6.5 reduced glomerular sclerosis and the extent of tubular dilation, whereas BZ/2.2 had little effect. CGS, especially at the high dose, virtually normalized the glomerular and tubular pathology. Compared with BZ, CGS 30440 treatment further diminished tubular dilation and proteinaceous cast formation. These tubular effects are consistent with some of the renal actions of ANP. The results from these studies indicate that CGS 30440, a combined ACEI/NEPI, conferred a greater renal protective effect than did ACE inhibition alone.

Predictors of outcome in patients with chronic back pain and low-grade spondylolisthesis.

STUDY DESIGN: Retrospective case series. OBJECTIVES: To determine the factors influencing symptom relief after uninstrumented posterolateral spinal fusion with or without decompression in adult patients with chronic back pain and previously asymptomatic low-grade isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA: The role of previously asymptomatic low-grade isthmic spondylolisthesis in chronic adult low back pain is unclear. Operative intervention in this setting is controversial. METHODS: Twenty-four consecutive adult patients with chronic low back pain and low-grade isthmic spondylolisthesis first detected during routine work-up of new onset low back pain underwent spinal fusion with or without decompression. The influence of active worker's compensation or litigation claims, radicular pain, concomitant laminectomy, age, gender, fusion to L4, intervertebral disc bulge, and pseudarthrosis were investigated. RESULTS: All 13 patients involved in worker's compensation claims or pending litigation had fair or poor results. Nine of 11 patients without such issues had good or excellent results. Although the strong association of worker's compensation with poor results made it difficult to assess the importance of other risk factors, the data suggest that good results may be more likely in patients with radiculopathy who undergo laminectomy. CONCLUSIONS: This investigation, although limited by a number of factors including small sample size and retrospective, unblinded review, suggests that active worker's compensation and litigation issues are associated strongly with poor results of operative management for chronic low back pain in adult patients with low-grade spondylolisthesis.

Prune-belly syndrome and other anomalies in a stillborn fetus with a ring X chromosome lacking XIST.

Ring X chromosomes that lack the X inactivation center and fail to be inactivated have been implicated as a cause of mental retardation and multiple congenital anomalies. We report on a stillborn fetus with karyotype mos45,X/46,X,r(X) and early urethral obstruction or prune-belly sequence, single umbilical artery, limb deficiency, horseshoe kidney, cardiac hypertrophy, persistent left superior vena cava, and axial skeleton abnormalities. Fluorescent in situ hydridization (FISH) studies confirmed that the ring chromosome is X-derived and demonstrated that it lacks the XIST locus. The findings in this fetus are discussed with regard to the spectrum of phenotypes associated with monosomy X and small ring X chromosomes.

Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression.

The induction of transplantation tolerance is one of the primary goals following solid organ transplantation. The combination of a single dose of rapamycin (RAPA) with a short course of cyclosporine (CsA) has been shown to induce transplantation tolerance in the nonfunctional rat heterotopic cardiac transplant model. The purpose of this study was to assess this effective induction protocol in a functional renal transplant model. Male ACI (RTl(a)) and Lewis (RT1(1)) rats were used as donor and recipients respectively. Allografts received a single RAPA dose of (1.5 mg/kg) combined with CsA (10 mg/kg) 12-14 hr prior to transplantation. CsA (5 mg/kg) was given daily on days +1 - +7. Untreated Lewis to Lewis isografts served as histological controls. Chimerism, assessed in recipient skin, and intragraft interleukin (IL) 10 expression was determined utilizing PCR and RT-PCR techniques respectively. Treated animals and isografts were sacrificed 120-130 days posttransplant for functional and histological evaluation. Allografts (n=9) were functionally tolerant with serum creatinine (0.77+/-0.1 vs. 0.88+/-0.1; P=0.275), blood urea nitrogen (37.6+/-4.6 vs. 23.3+/-1.9; P=0.123), and 24 hr protein excretion (27.0+/-4.4 vs. 17.9+/-5.2; P=0.131) similar to single kidney ACI controls. Histologically, 45% (4/9) allografts were indistinguishable from isografts with no evidence of rejection, and were considered immunologically tolerant. Donor/recipient chimerism was not detected. All immunologically tolerant allografts had evidence of intragraft IL-10 expression. Rejecting allografts and isografts did not express intragraft IL-10. This study confirms the efficacy of pre-engraftment single-dose RAPA combined with CsA in inducing true immunologic tolerance in this stringent functional renal transplant model. The expression of intragraft IL-10 in tolerant recipients suggests a Th-2 shift as the mechanism of tolerance in this model.

Effect of single-dose rapamycin-based immunosuppression on the development of cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy is the major cause of graft loss more than 1 year after transplantation. Daily rapamycin dosing has been shown to inhibit arterial intimal thickening caused by both alloimmune and mechanical injury. The combination of a single preoperative dose of rapamycin with a short (7 day) course of cyclosporine A has been shown to extend cardiac allograft survival, but its effects on the development of cardiac allograft vasculopathy has not been reported. METHODS: The ACI (RT1(a)) to Lewis (RT1(1)) heterotopic cardiac allograft model was used to assess the development of cardiac allograft vasculopathy and rejection. Treatment groups included nonimmunosuppressed control, cyclosporine A, cyclosporine A/donor-specific transfusion, and rapamycin/cyclosporine A. RESULTS: The addition of a single preoperative dose of rapamycin to a short course of cyclosporine A significantly reduced the prevalence of cardiac allograft vasculopathy in small (1.18 +/- 1.4 versus 0.05 +/- 0.3; p = 0.0001), medium (2.05 +/- 1.09 versus 0.26 +/- 0.62; p = 0.0001), and large (2.57 +/- 0.84 versus 1.43 +/- 1.2; p = 0.0008) vessels when compared with that in allografts treated with a single preoperative donor-specific transfusion and the same cyclosporine A schedule. Cardiac allograft vasculopathy did not develop in the nonimmunosuppressed control grafts or the group treated with cyclosporine A alone, because of the short survival times in these groups. In addition, there was a reduction of the rejection score in the rapamycin-treated allografts compared with that in the other treatment groups (4.0 +/- 0.0 versus 3.25 +/- 0.5; p = 0.0006). CONCLUSIONS: These results suggest that a single preoperative dose of rapamycin is efficacious in preventing the development of cardiac allograft vasculopathy, and continued immunosuppression with rapamycin may be unnecessary.

Cardiac allograft tolerance induction with limited immunosuppression.

We evaluated the efficacy and systemic toxicity of cyclosporine G, rapamycin, and cyclosporine A with multiple donor-specific blood transfusions in the stringent ACI to Lewis heterotopic cardiac transplant model. In addition, all animals received a 28-day post-operative course of cyclosporine A. Systemic toxicity was assessed by measuring recipient body weight at 30 and 60 days posttransplantation and at the time of graft rejection. Preengraftment cyclosporine G (10 mg/kg) resulted in a mean graft survival of 7.31 +/- 1.09 days (n=13; N.S. vs Control). A 10-day course of the novel immunosuppressant rapamycin (d4-14) combined with our standard 28-day cyclosporine A protocol resulted in a mean graft survival of 206.0 +/- 143.6 days (n=5; P < 0.05 vs Control). Furthermore, the rapamycin injection vehicle was found to have no intrinsic immunosuppressive activity or systemic toxicity. The addition of pre- (d-1) and post- (d7, 14, 21) engraftment donor-specific transfusion resulted in a mean allograft survival of 131.2 +/- 43.9 days. No significant difference in interval weight was observed in any of the experimental groups. We conclude that cyclosporine G is of little value in this experimental model. However, rapamycin combined with cyclosporine A provides effective immunosuppressive synergy without significant toxicity or the sensitization risk inherent in donor-specific blood transfusions.

Psychometric properties of a standardized-patient checklist and rating-scale form used to assess interpersonal and communication skills.

The results show that the SP checklist scores and the SP ratings of interpersonal and communication skills have comparable psychometric properties. The reliabilities of the five-item rating form (.76) and the single global rating of patient satisfaction (.70) were slightly higher than the reliability of the 17-item checklist (.65); this finding is of particular significance, given the greater length of the checklist. Also, the checklist scores and ratings appear to be measuring the same underlying dimension, with correlations of the checklist with the five ratings and with the single global rating being .82 and .81, respectively. Van der Vleuten and associates, in two excellent articles, noted a recent shift away from the use of subjective measures of clinical competence, such as rating scales, toward the use of presumably more objective measures, such as SP checklists. Their concern was that these objective measures may focus on somewhat trivial and easily measured aspects of the clinical encounter, and that more subtle but critical factors in clinical performance may be overlooked or ignored. They referred to such measurement as "objectified" rather than objective. The shift is based on the presumption that objective or objectified measurement is superior to subjective measurement, such as ratings, with respect to psychometric properties such as reliability. On the basis of a survey of several studies, though, the authors concluded that "objectified methods do not inherently provide more reliable scores" and "may even provide unwanted outcomes, such as negative effects on study behavior and triviality of the content being measured." The results of the present study support this conclusion, showing somewhat higher reliabilities for subjective ratings than for the objective (or perhaps objectified) checklist. Also, the high uncorrected correlations suggest that the more reliable ratings are measuring the same underlying dimension as are the checklist scores. The present study also illustrates the application of a recently proposed method for constructing a valid SP checklist, which would consist of items that best reflect global ratings of performance. In this study, the ratings were provided by the SPs themselves, but ratings could be obtained from faculty-physician experts who observe student performance on the SP case. Thus, performance on individual checklist items would be correlated with expert ratings, to identify the items that best predict the ratings. The checklist, then, would be constructed of just those items that best predict the ratings, and the checklist could be used for future testing without the need for further faculty ratings (yet the checklist scores would reflect the faculty ratings). With this approach, it would seem possible to construct checklists for history-taking and physical-examination skills, as well as for interpersonal and communication skills. Thus, the faculty ratings would provide a basis for case development and refinement, including scoring and standard setting, and scores on the checklist would serve as a proxy for the gold-standard faculty ratings. The study suggests that SP ratings may be more efficient and more reliable than SP checklists for assessing interpersonal and communication skills. The study also demonstrates that global ratings by SPs (or by expert physician observers) can provide a basis for SP-test construction.

Induction of long-term graft tolerance and donor/recipient chimerism.

We compared the effect of different immunosuppressive drug regimens on both mean and long-term allograft survival and the histologic appearance of donor/recipient chimeras in the ACI to Lewis rat heterotopic cardiac transplant model. Intraabdominal cardiac transplantation was performed in standard fashion and microchimerism was assessed using immunohistochemical staining of cut sections of recipient spleen and lymph nodes. All of the drug regimens studied resulted in excellent mean allograft survival. Furthermore, long-term (> 120 day) allograft survival was consistently observed in each group. In fact, many of the recipients continue to have functioning heterotopic grafts even as they approach the end of the natural life span of a Lewis rat. Mixed allogeneic chimerism, however, was not observed with 100% frequency despite the consistent induction of graft tolerance. This finding may be related to the immunosuppressive agents used or the sensitivity of the immunohistochemical assay. Therefore, the exact role, if any, of chimerism in the induction of graft tolerance remains unanswered.