Mayo Medical School Research Articles

Publications and Presentations Resulting From Required Research by Students at Mayo Medical School, 1976???2003

To determine the research productivity related to required research experiences during medical school. The authors studied the research productivity of the 998 graduates at Mayo Medical School who had participated in a required third-year medical school research experience (21, 18, or 17 weeks long) between 1976 and 2003. Outcomes were verified published research reports and abstracts, and presentations at scientific meetings. Research reports and abstracts related or unrelated to the required research were distinguished. Seventeen of the graduates were excluded when considering authorship of research reports (ambiguous data). Four hundred (41%) of the remaining 981 graduates published one or more research reports related to their required research experience, 176/998 (18%) published one or more abstracts related to their required research project, and 375/920 (41%) presented research findings at an extramural meeting at least once. Graduates who published a research report or abstract related to their required research or presented research at a scientific meeting published more research reports unrelated to their required research than did their peers who did not publish or present their required research (all P < .05). More graduates in the 21-week group were first authors (203/584; 35%) than were those in the 17/18-week group (60/336; 18%, P = .001), but other outcomes were similar for different durations (P > OR = .17). Required medical school research experiences facilitate tangible research products and may promote subsequent research productivity. Shorter experiences seem to yield outcomes similar to longer experiences.

Chymotrypsin B Cached in Rat Liver Lysosomes and Involved in Apoptotic Regulation through a Mitochondrial Pathway

Lysosomes can trigger the mitochondrial apoptotic pathway by releasing proteases. Here we report that a 25-kDa protein purified from rat liver lysosomes possesses a long standing potent Bid cleavage activity at neutral pH, and the truncated Bid can in turn induce rapid mitochondrial release of cytochrome c. This protease was revealed as chymotrypsin B by biochemical and mass spectrometric analysis. Although it was long recognized as a digestive protease exclusively secreted by the exocrine pancreas, our data support that it also expresses and intracellularly resides in rat liver lysosomes. Translocation of lysosomal chymotrypsin B into cytosol was triggered by apoptotic stimuli such as tumor necrosis factor-alpha, and intracellular delivery of chymotrypsin B protein induced apoptotic cell death with a potency comparable with cathepsin B, suggestive of a lysosomal-mitochondrial pathway to apoptosis regulated by chymotrypsin B following its release. Noteworthily, either knockdown of chymotrypsin B expression by RNA interference or pretreatment with chymotrypsin B inhibitor N-p-tosyl-L-phenylalanine chloromethyl ketone significantly reduced tumor necrosis factor-alpha-induce apoptosis. These results demonstrate for the first time that chymotrypsin B is not only restricted to the pancreas but can function intracellularly as a pro-apoptotic protease.

Sustained Relief of Leiomyoma Symptoms by Using Focused Ultrasound Surgery

For the MRgFUS Study Group Professor of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Mayo Clinic and Mayo Medical School, Rochester, Minnesota

Early Clinical Experiences from Studentsʼ Perspectives: A Qualitative Study of Narratives

To gain insight into how early clinical experiences contribute to medical students' professional development. Qualitative content analysis of second-year Mayo Medical School students' reflective journal essays pertaining to their first experiences with inpatients (from 2002 to 2004) was done using a grounded theory approach. The apprenticeship model of professional learning (knowledge and cognitive abilities, technical skills, and ethical standards) and perspectives from learning theory provided the conceptual framework. Major themes were identified, and member checking and interrater reliability was assessed to support the validity and reliability of the content analysis. Four major themes related to the purposes that the early clinical experiences with patients served for students were identified in analysis of reflections from 76 students (participation rate 95%). The themes were issues related to relationships and learning in early encounters with hospitalized patients; integration with learning in the entire curriculum; aspects of doctoring learned; and affiliation with the physician role and professional development. Select quotes illustrate these themes and provide thick description. Member checking supported the analysis; interrater reliability was 91%. Early hospital-based clinical experiences provide opportunities for apprenticeships in the habits of the head, hand, and heart. Medical students' growth and learning occurs within these apprenticeship domains through contextual experiential learning.

Can a Flexible Medical Curriculum Promote Student Learning and Satisfaction?

Medical education is trending towards an outcome-based curriculum that prepares medical graduates to excel in a rapidly evolving, team-centred healthcare delivery system. The Mayo Medical School (MMS) has recently redesigned its curriculum to introduce early clinical relevance, optimise course integration, provide flexibility and promote active learning. This study aims to evaluate the role that curricular flexibility plays in students' perceived learning, satisfaction and performance. First-year students completed a 5-point Likert scale survey regarding satisfaction with and perceived learning from various components of the flexible curriculum during 2 different academic blocks. Students' academic performance was assessed by a National Board of Medical Examiners (NBME) Subject Examination after each block. In comparing student-rated satisfaction and perceived learning from didactics versus other curricular components for Block 3 (Pathology and Immunology) and Block 5 (Gross Anatomy and Radiology), students rated didactics higher in all cases in which there was a statistically significant difference in the ratings. There was a statistically significant positive correlation between the amount learned and satisfaction for all curricular components with the exception of Block 5 independent study. During Block 3, only interest in the subject matter correlated positively with the NBME score, while during Block 5, only time spent in class correlated negatively with the NBME score. Although various components of the flexible curriculum do not appear to affect satisfaction and perceived learning, their potential influence on graduate outcomes, in terms of delivering healthcare providers who are patient-centred, creative thinkers and compassionate leaders should not be discounted.

Traumatic Obliterative Urethral Strictures in Pediatric Patients: Failure of the Cut to Light Technique at Long-Term Followup

The cut to light procedure or antegrade and retrograde urethroscopy with endoscopic incision of obliterative urethral strictures is an accepted method of treating posterior urethral distraction injuries. We report long-term followup on 22 pediatric patients treated with this technique. The records of all pediatric patients with a posterior urethral distraction injury treated from 1986 through 2006 were reviewed. The cut to light procedure was performed for obliterative strictures less than 1 cm via a cold knife or laser in 11 patients each. A urethral catheter was left in situ for 3 weeks. Patients were then followed a minimum of 2 years. A total of 22 patients at a median age of 11 years (range 3 to 16) were treated. Followup revealed stricture recurrence in all patients. Median time to recurrence was 3 months after catheter removal (range 5 days to 1 year). Although intermittent catheterization to maintain patency was attempted in all patients, the development of impassable urethral strictures in 16 (73%) and complaints of chronic pain with catheterization in 4 (18%) led to end-to-end urethroplasty. Successful reconstruction with open surgery was achieved in 19 of 20 patients (95%). Two patients (9%) maintained urethral patency with intermittent catheterization. In children with obliterative posterior urethral distraction injuries a cut to light procedure had a long-term success rate of 0%. All patients required daily intermittent catheterization (9%) or formal urethral reconstruction (91%) to maintain patency. We would strongly recommend against treating pediatric obliterative urethral strictures with a cut to light procedure.

Prolonged delays for research training in medical school are associated with poorer subsequent clinical knowledge.

Complementary degree programs and research training are important alternative tracks in medical school that typically interrupt the traditional MD curriculum. Examine effects of such a break on clinical knowledge after reentry into the MD curriculum. Retrospective cohort study. Three hundred and two graduates of Mayo Medical School. Compared years of delay between the second and third years of medical school with third year clerkship grades, National Board of Medical Examiner's (NBME) Subject Examinations, and United States Medical License Exam (USMLE) Step 2. 258, 13, and 31 students spent 0, 1, or > or = 3 years pursuing research between the second and third year. Baseline measures of knowledge before matriculation and before the third year were similar between groups. Whereas a 1-year delay had no significant effect, a > or = 3-year delay was associated with fewer clerkship honors and lower NBME Medicine, Pediatrics, and Psychiatry percentiles compared to no delay (all p < .05). Students with a > or = 3-year delay had a 77% reduction in the odds of honors in Medicine. For each year of delay beyond 3, students' third-year NBME Medicine, Neurology, Obstetrics and Gynecology, and Psychiatry scores decreased as did USMLE Step 2 scores (r = -.38 to -.50, p < .05). Delays of > or = 3 years between the second and third years of medical school are associated with lower grades and scores on clinical knowledge tests. Further research is needed to determine the optimal timing of research training and develop effective interventions to facilitate reentry into the medical school curriculum.

Endoscopic Management of Upper Tract Urothelial Carcinoma in Patients With a History of Bladder Urothelial Carcinoma

Endoscopic management of renal pelvis and ureteral urothelial carcinoma is gaining acceptance as a conservative treatment modality. Patients with a history of bladder urothelial carcinoma are at high risk for upper tract recurrence. We evaluate the role of endoscopic management of upper tract urothelial carcinoma in patients with a history of primary bladder urothelial carcinoma. We retrospectively reviewed 90 patients with a history of primary bladder urothelial carcinoma who underwent endoscopic treatment of localized upper tract urothelial carcinoma between 1983 and 2004. Median patient age at diagnosis was 73 years (range 50 to 90). A total of 13 (14.4%) patients previously underwent cystectomy. With a median followup of 4.3 years (range 0.1 to 17), 105 upper tract urothelial carcinoma recurrences developed in 55 patients at a mean of 0.6 years (range 22 days to 5.9 years). Of these recurrences 76 were amenable to endoscopic management while 29 required nephroureterectomy. In 38 patients there were 91 bladder recurrences. At last followup 48 patients died, 17 of urothelial carcinoma at a median of 3.4 years (range 1 to 10). Cancer specific survival at 5 years for this cohort was 71.2%. Risk of death from urothelial carcinoma was significantly associated with stage (RR 3.23) and grade (RR 4.05) of upper tract urothelial carcinoma, imperative indication (RR 4.30), and treatment of bladder urothelial carcinoma with cystectomy (RR 3.34). Endoscopic management of upper tract urothelial carcinoma in patients with primary bladder urothelial carcinoma demonstrates a significant local recurrence rate. Furthermore, 5-year cancer specific survival is low. These patients represent a high risk cohort requiring strict ureteroscopic followup after endoscopic management is instituted.

Educating to Improve Patient Care: Integrating Quality Improvement Into a Medical School Curriculum

A curriculum focused on disease and the management of disease is no longer adequate for training physicians who are expected to practice in an environment where medical errors, system shortcomings, and physician and practice scorecards are the norm. This article describes a longitudinal curriculum on quality improvement that was integrated into the existing curriculum at Mayo Medical School, from years I through IV, through collaboration with 13 different course and clerkship directors. The curriculum is being taught through exercise-based discussions, video sessions followed by debriefing, simulations, case-based discussions, and lectures. This curriculum prepares physicians in training to be knowledgeable about common systems issues and medical errors in clinical practice and has the potential for application in undergraduate medical education.

Keith Lindor is New Editor-In-Chief of H epatology

Keith Lindor is New Editor-In-Chief of H epatology

The Objective Structured Clinical Examination as an Educational Tool in Patient Safety

The Objective Structured Clinical Examination (OSCE) is an assessment tool characterized by the use of "lay" people trained to respond to questions in a standardized fashion. The learner's performance is observed and scored against a checklist of responses or behaviors. An OSCE station related to the communication and management of prescription errors was introduced in 2003 as part of a quality improvement (QI) curriculum at Mayo Medical School. All 42 third-year medical students took part in this pilot study, which was designed to evaluate the usefulness of an OSCE station as an assessment and educational tool for managing prescription errors. Thirty-three (76.7%) students agreed that the OSCE station enhanced their awareness of medication errors. Thirty (71.4%) students felt that their comfort level with communicating prescription errors to patients increased. Specific feedback regarding root cause analysis, collaboration with the pharmacist for error analysis, interpersonal and communication skills feedback from the faculty, and use of the standardized patient and of an actual prescription that led to a medication error, were found especially valuable. This pilot study demonstrates the potential use of the OSCE as an assessment and educational tool in QI and patient safety. The OSCE approximates a "live clinical setting" and provides an opportunity for the assessment of situational awareness and response, as well as formative and summative feedback to students.

The Benefits of Pass-Fail Grading on Stress, Mood, and Group Cohesion in Medical Students

To objectively measure the effect of a pass-fail grading system on stress, mood, group cohesion, and test anxiety in medical students. Beginning with the class of 2006, the Mayo Medical School, Rochester, Minn, changed the grading system for first-year courses from a 5-interval grading system to a pass-fail grading system. Students in the previous class of 2005, who were graded using a 5-interval system during their first year of medical school, were compared with students in the class of 2006. Using a prospective study design, the 2 groups were compared at the end of both the first year and the second year of medical school on the Perceived Stress Scale, Profile of Mood States, Perceived Cohesion Scale, Test Anxiety Inventory, and (after year 2) the United States Medical Licensing Examination Step 1. Data collection occurred in 2002 and 2003 with the class of 2005 and in 2003 and 2004 with the class of 2006. Students graded with the pass-fail system had less perceived stress (median, 15.0 vs 21.0; P-.01) and greater group cohesion (median, 34.5 vs 30.0; P=.02) at the end of their second year of coursework than their 5-interval graded peers. The pass-fail group had better mood (median, 46.5) than the graded group (median, 64.0), but this difference was not statistically significant (P=.07). No significant differences were found between the 2 groups in test-taking anxiety or in United States Medical Licensing Examination Step 1 board scores. Pass-fail grading may reduce stress and increase group cohesion in medical students compared with traditional 5-interval grading.

The Role of Nephron Sparing Surgery for Metastatic (pM1) Renal Cell Carcinoma

Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.

A new horizon in the treatment of right ventricular failure and pulmonary hypertension associated with acute respiratory distress syndrome?*

Department of Medicine, Maricopa Medical Center, Phoenix, AZ (Carlson) University of Arizona and Mayo Medical School, Phoenix, AZ (Emmans)

Kidney tumours excel at evasion

Kidney-cell carcinomas that carry immune inhibitory proteins on their surface are more aggressive and lethal than tumours without such protective armour, according to a new study from Eugene Kwon and colleagues at the Mayo Medical School (Rochester, MN, USA; Proc Natl Acad Sci USA 2006; 103: 10391–96). Researchers showed that tumours expressing the T-cell silencing proteins B7H1 and B7H4 had faster progression and gave poorer survival. These results suggest that neutralisation of B7H1 and B7H4 could disarm tumour defences and boost host immunity.

Chronic Osteoarthritis

Chronic Osteoarthritis

Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness: Sengupta S, Lohse CM, Leibovich BC, Frank I, Thompson RH, Webster WS, Zincke H, Blute ML, Cheville JC, Kwon ED, Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, MN

Background Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow-up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. Methods The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. Results Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56–6.09; P Conclusions Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.

A SCORING ALGORITHM TO PREDICT SURVIVAL FOR PATIENTS WITH METASTATIC CLEAR CELL RENAL CELL CARCINOMA: A STRATIFICATION TOOL FOR PROSPECTIVE CLINICAL TRIALS

We developed a clinically useful scoring algorithm to predict cancer specific survival for patients with clear cell metastatic renal cell carcinoma (RCC). We studied 727 patients treated with radical nephrectomy for clear cell RCC from 1970 to 2000 who had distant metastases at nephrectomy (285) or in whom metastases subsequently developed (442). A scoring algorithm to predict cancer specific survival was developed using the regression coefficients from a Cox proportional hazards model. There were 606 deaths from clear cell RCC at a median of 1.0 years (range 0 to 14) following metastatic RCC. Constitutional symptoms at nephrectomy (+2), metastases to the bone (+2) or liver (+4), metastases in multiple simultaneous sites (+2), metastases at nephrectomy (+1) or within 2 years of nephrectomy (+3), complete resection of all metastatic sites (-5), tumor thrombus level I to IV (+3), and the primary pathological features of nuclear grade 4 (+3) and histological tumor necrosis (+2) were significantly associated with death from RCC. All patients started with a score of 0 and points were added or subtracted as indicated in parentheses. Cancer specific survival rates at 1 year were 85.1%, 72.1%, 58.8%, 39.0%, and 25.1%, respectively, for patients with scores of -5 to -1, scores of 0 to 2, scores of 3 to 6, scores of 7 or 8, and scores of 9 or more. This scoring algorithm can be used to predict cancer specific survival for patients with metastatic clear cell RCC.

COMPLICATIONS OF CONTEMPORARY OPEN NEPHRON SPARING SURGERY: A SINGLE INSTITUTION EXPERIENCE

Open nephron sparing surgery (NSS) is now the standard of care for small renal tumors irrespective of overall renal function. More recently laparoscopic NSS with hilar clamping has emerged, albeit with relatively longer ischemic times. We reviewed our experience with contemporary open NSS, comparing complication rates to those of historical controls and updating data for comparison with minimally invasive procedures. From 1985 to 2001, 823 open NSSs were performed at our institution. Early (within 30 days of NSS) and late (30 days to 1 year) complications were compared using the chi-square and Wilcoxon rank sum tests between procedures performed in 1985 to 1995 (control group of 343 patients) and 1996 to 2001 (contemporary group of 480). In the control vs the contemporary group there were significant decreases in intraoperative blood loss (median 550 vs 350 cc, p <0.001), chronic renal insufficiency/failure (14.6% vs 8.1%, p = 0.003), dialysis need (7.0% vs 2.1%, p <0.001) and any early (13.4% vs 6.9%, p = 0.002) or late (32.4% vs 24.6%, p = 0.014) complication. In the contemporary group 50% of patients did not require pedicle clamping, 32% underwent warm ischemia (median 12 minutes) and 18% underwent cold ischemia (median 27 minutes). In addition, patients with a warm ischemia time of 20 minutes or less had fewer early complications than patients with greater than 20 minutes of ischemia, although this did not attain statistical significance (3.8% vs 13.6%, p = 0.063). Complications resulting from open NSS have significantly decreased with time. Contemporary open NSS is associated with minimal morbidity, and decreases the need for pedicle clamping and overall ischemia time.

The fetal dose limit for flight personnel should be 1 mSv over the gestation period, rather than 5 mSv as recommended by the NCRP

The fetal dose limit for flight personnel should be 1 mSv over the gestation period, rather than 5 mSv as recommended by the NCRP