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Background: Previous studies have demonstrated an association between malnutrition and poor outcomes. The primary objective of this study was to explore the difference in the composite end point of readmission rate or mortality rate between hospitalized veterans with and without malnutrition., Materials and Methods: This was a retrospective chart review comparing veterans with malnutrition based on a modified version of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition consensus characteristics that used 5 of the 6 clinical characteristics to a matched control group of nonmalnourished veterans based on age, admitting service, and date of admission who were admitted between August 1, 2012, and December 1, 2014. Data were extracted from the medical record. Multivariate analysis was used to identify predictors of outcomes., Results: In total, 404 patients were included in the final analysis. All end points were found to be statistically significant. The malnourished group was more likely to meet the composite end point (odds ratio [OR], 5.3), more likely to be readmitted within 30 days (OR, 3.4), more likely to die within 90 days of discharge (OR, 5.5), and more likely to have a length of stay >7 days (OR, 4.3) compared with the nonmalnourished group. Length of stay was significantly longer in the malnourished group, 9.80 (11.5) vs 4.38 (4.5) days., Conclusion: Malnutrition was an independent risk factor for readmission within 30 days or death within 90 days of discharge. Malnourished patients had higher rates of readmission, higher mortality rates, and longer lengths of stay and were more likely to be discharged to nursing homes.

Evidence indicates that the largest volume of hospital readmissions occurs among patients with preexisting chronic conditions. Identifying these patients can improve the way hospital care is delivered and prioritize the allocation of interventions. In this retrospective study, we identify factors associated with readmission within 30 days based on claims and administrative data of nine hospitals from 2005 to 2012. We present a data inclusion and exclusion criteria to identify potentially preventable readmissions. Multivariate logistic regression models and a Cox proportional hazards extension are used to estimate the readmission risk for 4 chronic conditions (congestive heart failure [CHF], chronic obstructive pulmonary disease [COPD], acute myocardial infarction, and type 2 diabetes) and pneumonia, known to be related to high readmission rates. Accumulated number of admissions and discharge disposition were identified to be significant factors across most disease groups. Larger odds of readmission were associated with higher severity index for CHF and COPD patients. Different chronic conditions are associated with different patient and case severity factors, suggesting that further studies in readmission should consider studying conditions separately.

Background: Important barriers for widespread use of health information exchange (HIE) are usability and interface issues. However, most HIEs are implemented without performing a needs assessment with the end users, healthcare providers. We performed a user needs assessment for the process of obtaining clinical information from other health care organizations about a hospitalized patient and identified the types of information most valued for medical decision-making., Methods: Quantitative and qualitative analysis were used to evaluate the process to obtain and use outside clinical information (OI) using semi-structured interviews (16 internists), direct observation (750 h), and operational data from the electronic medical records (30,461 hospitalizations) of an internal medicine department in a public, teaching hospital in Tampa, Florida., Results: 13.7 % of hospitalizations generate at least one request for OI. On average, the process comprised 13 steps, 6 decisions points, and 4 different participants. Physicians estimate that the average time to receive OI is 18 h. Physicians perceived that OI received is not useful 33-66 % of the time because information received is irrelevant or not timely. Technical barriers to OI use included poor accessibility and ineffective information visualization. Common problems with the process were receiving extraneous notes and the need to re-request the information. Drivers for OI use were to trend lab or imaging abnormalities, understand medical history of critically ill or hospital-to-hospital transferred patients, and assess previous echocardiograms and bacterial cultures. About 85 % of the physicians believe HIE would have a positive effect on improving healthcare delivery., Conclusions: Although hospitalists are challenged by a complex process to obtain OI, they recognize the value of specific information for enhancing medical decision-making. HIE systems are likely to have increased utilization and effectiveness if specific patient-level clinical information is delivered at the right time to the right users.

Laboratory tests are a primary resource to diagnose patient's diseases. However, physicians often make decisions based on the available information, which commonly includes the last test results as a static picture and have limited perspective of the role of trends in commonly measured parameters in enhancing the diagnostic process. By providing a dynamic patient profile the diagnosis could be more accurate and, as a consequence, physicians could anticipate changes in recovery trajectory and prescribe interventions more effectively. Intensive care unit (ICU) patients need continuous monitoring, which commonly includes the assessment of several blood components. One of these components is the platelet count which is used in assessing blood clotting. However, platelet counts represent a dynamic equilibrium of many simultaneous processes including altered capillary permeability, inflammatory cascades, as well as the coagulation process. To characterize the value of dynamic changes in platelet counts we applied analytic methods to datasets of critically ill patients in (i) a homogeneous population of ICU cardiac surgery patients, where an observation appears to be predictive of patient's complications and mortality and (ii) a heterogeneous group of ICU patients to confirm the previous observation.

Background: The medical community has only recently begun to address how human error affects patient safety. In order to confront human error in medicine, there is a need to teach students who are entering the health professions how potential errors may manifest and train them to prevent or mitigate these problems., Purpose: The objective is to describe a semester-long, interdisciplinary, human error and patient safety course taught at the University of South Florida., Methods: Six interdisciplinary groups, composed of students from five of the university's colleges, were formed. The curriculum consisted of expert lecturers, readings, case studies, and analysis of patient safety problems. Students were evaluated based on their group's work on the final project and peer evaluations., Results: Nursing students scored the highest in each category evaluated. Physicians and medical students had the lowest evaluations in team participation and active engagement. All students rated the course highly and indicated that it enhanced their ability to work in interprofessional settings., Conclusions: The students showed improved knowledge and substantive skill level relative to patient safety and human error concepts. Working in interdisciplinary teams gave the students a better understanding of the role each discipline can have in improving health care systems and health care delivery.

Purpose: To reduce errors in surgery using a resident training program based on a taxonomy that highlights three kinds of errors: judgment, inattention to detail, and problem understanding., Method: The training program module at the University of South Florida incorporated a three-item situational judgment test, video training (which included a lecture and behavior modeling), and role-plays (in which residents participated and received feedback from faculty). Two kinds of outcome data were collected from 33 residents during 2006-2007: (1) behaviors during the training and (2) on-the-job surgical complication records 12 months before and 6 months after training. For the data collected during training, participants were assigned to a condition (19 video condition, 13 control condition); for the data collected on the job, an interrupted time series design was used., Results: Data from 32 residents were analyzed (one resident's data were excluded). One of the situational judgment items improved significantly over time (d = 0.45); the other two did not (d = 0.36, 0.25). Surgical complications and errors decreased over the course of the study (the correlation between complications and time in months was r = -0.47, for errors and time, r = -0.55). Effects of video behavior modeling on specific errors measured during role-plays were not significant (effect sizes for binary outcomes were phi = -0.05 and phi = 0.01, and for continuous outcomes, d ranged from -0.02 to 0.34)., Conclusions: The training seemed to reduce errors in surgery, but the training had little effect on the specific kinds of errors targeted during training.

Objective: This study prospectively assesses the underlying errors contributing to surgical complications over a 12-month period in a complex academic department of surgery using a validated scoring template., Background: Studies in "high reliability organizations" suggest that systems failures are responsible for errors. Reports from the aviation industry target communication failures in the cockpit. No prior studies have developed a validated classification system and have determined the types of errors responsible for surgical complications., Methods: A classification system of medical error during operation was created, validated, and data collected on the frequency, type, and severity of medical errors in 9,830 surgical procedures. Statistical analysis of concordance, validity, and reliability were performed., Results: Reported major complications occurred in 332 patients (3.4%) with error in 78.3%: errors in surgical technique (63.5%), judgment errors (29.6%), inattention to detail (29.3%), and incomplete understanding (22.7%). Error contributed more than 50% to the complication in 75%. A total of 13.6% of cases had error but no injury, 34.4% prolongation of hospitalization, 25.1% temporary disability, 8.4% permanent disability, and 16.0% death. In 20%, the error was a "mistake" (the wrong thing), and in 58% a "slip" (the right thing incorrectly). System errors (2%) and communication errors (2%) were infrequently identified., Conclusions: After surgical technique, most surgical error was caused by human factors: judgment, inattention to detail, and incomplete understanding, and not to organizational/system errors or breaks in communication. Training efforts to minimize error and enhance patient safety must address human factor causes of error.

Background: Adrenalectomy rates seem to be increasing in Florida, possibly due to increased availability of laparoscopic adrenalectomy, identification of incidentalomas, and access to care for minorities. We hypothesized that the rate of adrenalectomies in Florida increased from 1998-2005 while characteristics of patients, diagnoses, operations, and operating physicians changed over this period., Methods: Prospectively-collected, mandatory-reported, hospital discharge data for all inpatient adrenalectomies undertaken in Florida from 1998-2005 were obtained along with Florida census and physician certification and education data. Characteristics of adrenalectomy patients, diagnoses, operations, and physicians were analyzed., Results: 1816 adrenalectomies were available for analysis. Yearly rates of adrenalectomy nearly doubled from 1.20 to 2.26 per 100,000 Florida residents (P = .0024). Overall, patient characteristics such as demographics, indications and comorbidities did not change, whereas hospital charges increased and length-of-stay (LOS) significantly decreased (P = .0031 and P < .0001, respectively). There was a non-significant trend toward a yearly increase in physician volume and an inverse relationship between physician volume categories and mean LOS (P < .0001)., Conclusions: The rate of adrenalectomies is increasing in Florida. This increase was not associated with distinct trends in patient characteristics, although a significant decrease in LOS was identified. As these trends continue and adrenalectomy is applied more liberally, indications for adrenalectomy may need to be re-evaluated.

Residency is a time of stress and turmoil for many residents. The stresses are varied and great, often involving both personal and professional issues. One institutional mechanism that has been shown to help residents cope with stress is the use of residents' wellness, or assistance, programs. The University of South Florida (USF) College of Medicine developed the USF Residency Assistance Program (RAP) in 1997, modeled after business employee assistance programs but tailored to enhance the well-being of residents. The program was developed in an organized, thoughtful manner starting with a Request for Proposals to all local employee assistance programs and the selection of one of these to run the program. The RAP is broad-based, readily available, easily accessible, totally voluntary and confidential, and not reportable to the state board of medicine. It is well integrated into all residency programs and has had excellent acceptance from the administration; information about access to the RAP is available to all residents through multiple venues. The cost is minimal, at only seven cents a day per resident. The authors present data from the eight years the RAP has been operating, including information on program use, referral rates, acceptance, and types of problems encountered. One suicide occurred during this time period, and the RAP provided a significant role in grief counseling. Assistance programs are critical to the well-being of residents. The USF program presents a model that can be used by other programs around the country.

Background: Work hour guidelines and core competencies were introduced to improve surgical education and are changing the landscape of surgical training. We sought to examine perceptions and attitudes regarding the impetus and impact associated with these changes., Materials and Methods: Anonymous surveys were distributed to faculty and surgeons-in-training in an Accreditation Council for Graduate Medical Education, university-based, training program., Results: Faculty (F, n = 30) and trainees (T, n = 30) agree that lifestyle expectations and long work hours are the principal issues facing surgical education (F = 80%, T = 56%; P = 0.03). Implementation of ACGME guidelines is perceived as NOT improving patient care or clinical experience (F = 100%, T = 90%; P = 0.03) while reducing operative experience (F = 50%, T = 70%). More faculty (>80%) than trainees (33%) are concerned that ACGME guidelines will diminish patient care experiences. Although most (F = 77%, T = 83%; P = NS) agree that hiring additional providers will improve guideline compliance, many oppose ACGME guideline implementation fearing a loss of professionalism. Although both (F = 50%, T = 47%) admonish deficient interpersonal and communication skills as the major impediment to implementing ACGME guidelines, opinions regarding implementation differ. Most faculty (67%) believe ACGME-imposed deadlines are the most influential reason; however, trainees (57%) believe guidelines should be promptly implemented to address long-awaited changes in work environment and surgical graduate medical education., Conclusions: Although faculty and trainees' perception of the issues surrounding ACGME guidelines converge, perception of changes following implementation is quite divergent. For successful implementation, leadership must address prevailing attitudes and set realistic expectations. These trends have important implications for planning the future of surgical education, unifying multi-generational colleagues, and improving systems-based practice.

Surgical education is in the process of tumultuous change. Mastering this change will require a new set of competencies and a new understanding of the medical education process. While accreditation agencies are rapidly working to define the new criteria and benchmarks, training programs are quickly pulling together curricula, objectives, and evaluation tools. Yet much has already been learned in other complex, high-risk activities. Blue water sailing, ocean racing, and trans-Atlantic crossing are all activities that require a renewed form of leadership and an understanding of how knowledge, skill, and behavior come together to define the competent sailor. Ideas learned in such endeavors may assist the surgical educator in defining the horizons and the hazards of this uncharted voyage.

Atrial natriuretic peptide (ANP) released from enterochromaffin cells helps regulate antral somatostatin secretion, but the mechanisms regulating ANP secretion are not known. We superfused rat antral segments with selective neural agonists/antagonists to identify the neural pathways regulating ANP secretion. The nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) stimulated ANP secretion; the effect was abolished by hexamethonium but doubled by atropine. Atropine's effect implied that DMPP activated concomitantly cholinergic neurons that inhibit and noncholinergic neurons that stimulate ANP secretion, the latter effect predominating. Methacholine inhibited ANP secretion. Neither bombesin nor vasoactive intestinal polypeptide stimulated ANP secretion, whereas pituitary adenylate cyclase-activating polypeptide (PACAP)-27, PACAP-38, and maxadilan [PACAP type 1 (PAC1) agonist] each stimulated ANP secretion. The PAC1 antagonist M65 1) abolished PACAP-27/38-stimulated ANP secretion; 2) inhibited basal ANP secretion by 28 +/- 5%, implying that endogenous PACAP stimulates ANP secretion; and 3) converted the ANP response to DMPP from 109 +/- 21% above to 40 +/- 5% below basal, unmasking the cholinergic component and indicating that DMPP activated PACAP neurons that stimulate ANP secretion. Combined atropine and M65 restored DMPP-stimulated ANP secretion to basal levels. ANP secretion in the antrum is thus regulated by intramural cholinergic and PACAP neurons; cholinergic neurons inhibit and PACAP neurons stimulate ANP secretion.

Objective: To determine whether the investment in postgraduate education and training places patients at risk for worse outcomes and higher costs than if medical and surgical care was delivered in nonteaching settings., Summary Background Data: The Veterans Health Administration (VA) plays a major role in the training of medical students, residents, and fellows., Methods: The database of the VA National Surgical Quality Improvement Program was analyzed for all major noncardiac operations performed during fiscal years 1997, 1998, and 1999. Teaching status of a hospital was determined on the basis of a background and structure questionnaire that was independently verified by a research fellow. Stepwise logistic regression was used to construct separate models predictive of 30-day mortality and morbidity for each of seven surgical specialties and eight operations. Based on these models, a severity index for each patient was calculated. Hierarchical logistic regression models were then created to examine the relationship between teaching versus nonteaching hospitals and 30-day postoperative mortality and morbidity, after adjusting for patient severity., Results: Teaching hospitals performed 81% of the total surgical workload and 90% of the major surgery workload. In most specialties in teaching hospitals, the residents were the primary surgeons in more than 90% of the operations. Compared with nonteaching hospitals, the patient populations in teaching hospitals had a higher prevalence of risk factors, underwent more complex operations, and had longer operation times. Risk-adjusted mortality rates were not different between the teaching and nonteaching hospitals in the specialties and operations studied. The unadjusted complication rate was higher in teaching hospitals in six of seven specialties and four of eight operations. Risk adjustment did not eliminate completely these differences, probably reflecting the relatively poor predictive validity of some of the risk adjustment models for morbidity. Length of stay after major operations was not consistently different between teaching and nonteaching hospitals., Conclusion: Compared with nonteaching hospitals, teaching hospitals in the VA perform the majority of complex and high-risk major procedures, with comparable risk-adjusted 30-day mortality rates. Risk-adjusted 30-day morbidity rates in teaching hospitals are higher in some specialties and operations than in nonteaching hospitals. Although this may reflect the weak predictive validity of some of the risk adjustment models for morbidity, it may also represent suboptimal processes and structures of care that are unique to teaching hospitals. Despite good quality of care in teaching hospitals, as evidenced by the 30-day mortality data, efforts should be made to examine further the structures and processes of surgical care prevailing in these hospitals.

Atrial natriuretic peptide (ANP) gene expression was localized in the rat gastric antrum using immunohistochemistry and in situ hybridization to mucosal cells in the lower portion of the antropyloric glands. Colocalization of immunoreactive ANP, long-acting natriuretic peptide, i.e., proANP-(1-30), and serotonin in these cells identified them to be enterochromaffin cells. Fasting for 72 h in 8-mo-old (adult) rats produced a significant (P < 0.05) decrease in the levels of ANP prohormone mRNA, immunoreactive proANP-(1-30) and ANP to approximately 33% of that of fed rats. Fasting in 1-mo-old rats had no effect on these parameters. Transcripts for natriuretic peptide receptor subtypes NPR-A, NPR-B, and NPR-C were found in both mucosa and muscle tissues of the antrum. ANP, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) stimulated the production of cGMP in antral mucosa in vitro with a potency of ANP > BNP >> CNP, suggesting that these receptors were functional. We conclude that fasting decreases ANP prohormone mRNA and its gene products, long-acting natriuretic peptide, and ANP in the antrum of adult rats.

Objective: To examine, in the Veterans Health Administration (VHA), the relation between surgical volume and outcome in eight commonly performed operations of intermediate complexity., Summary Background Data: In multihospital health care systems such as VHA, consideration is often given to closing low-volume surgical services, with the assumption that better surgical outcomes are achieved in hospitals with larger surgical volumes. Literature data to support this assumption in intermediate-complexity operations are either limited or controversial., Methods: The VHA National Surgical Quality Improvement Program data on nonruptured abdominal aortic aneurysmectomy, vascular infrainguinal reconstruction, carotid endarterectomy (CEA), lung lobectomy/pneumonectomy, open and laparoscopic cholecystectomy, partial colectomy, and total hip arthroplasty were used. Pearson correlation, analysis of variance, mixed effects hierarchical logistic regression, and automatic interaction detection analysis were used to assess the association of annual procedure/specialty volume with risk-adjusted 30-day death (and stroke in CEA)., Results: Eight major surgical procedures (68,631 operations) were analyzed. No statistically significant associations between procedure or specialty volume and 30-day mortality rate (or 30-day stroke rate in CEA) were found., Conclusions: In VHA hospitals, the procedure and surgical specialty volume in eight prevalent operations of intermediate complexity are not associated with risk-adjusted 30-day mortality rate from these operations, or with the risk-adjusted 30-day stroke rate from CEA. Volume of surgery in these operations should not be used as a surrogate for quality of surgical care.

Changes in medicine, medical education, and technology have influenced graduate medical education (GME) and have altered many traditional concepts of resident training. Three issues in particular have led to changes. The first is the shortage of time that academic and community physicians have to devote to medical teaching because of the demands to bring in revenue through clinical practice. The second is the limited exposure that residents have to various medical conditions due to a shift in training venues from hospitals to ambulatory care settings. Last is residents' lack of training in using information technologies. The resultant deficits the exist in GME make it more difficult for residents to practice medicine in the most efficient manner. Hence, there is a need for health care professionals' education to address the coming demands of the 21st century. Instructional computer technology can be useful in bridging this gap. Intranets, internal organizational networks, are private versions of the World Wide Web that are often available only to members of a particular organization. This paper reviews changes in medicine and medical education, describes how instructional intranets can be incorporated into GME, and discusses the impact intranet and Internet technologies can have on GME.

Objective: To provide reliable risk-adjusted morbidity and mortality rates after major surgery to the 123 Veterans Affairs Medical Centers (VAMCs) performing major surgery, and to use risk-adjusted outcomes in the monitoring and improvement of the quality of surgical care to all veterans., Summary Background Data: Outcome-based comparative measures of the quality of surgical care among surgical services and surgical subspecialties have been elusive., Methods: This study included prospective assessment of presurgical risk factors, process of care during surgery, and outcomes 30 days after surgery on veterans undergoing major surgery in 123 medical centers; development of multivariable risk-adjustment models; identification of high and low outlier facilities by observed-to-expected outcome ratios; and generation of annual reports of comparative outcomes to all surgical services in the Veterans Health Administration (VHA)., Results: The National VA Surgical Quality Improvement Program (NSQIP) data base includes 417,944 major surgical procedures performed between October 1, 1991, and September 30, 1997. In FY97, 11 VAMCs were low outliers for risk-adjusted observed-to-expected mortality ratios; 13 VAMCs were high outliers for risk-adjusted observed-to-expected mortality ratios. Identification of high and low outliers by unadjusted mortality rates would have ascribed an outlier status incorrectly to 25 of 39 hospitals, an error rate of 64%. Since 1994, the 30-day mortality and morbidity rates for major surgery have fallen 9% and 30%, respectively., Conclusions: Reliable, valid information on patient presurgical risk factors, process of care during surgery, and 30-day morbidity and mortality rates is available for all major surgical procedures in the 123 VAMCs performing surgery in the VHA. With this information, the VHA has established the first prospective outcome-based program for comparative assessment and enhancement of the quality of surgical care among multiple institutions for several surgical subspecialties. Key features to the success of the NSQIP are the support of the surgeons who practice in the VHA, consistent clinical definitions and data collection by dedicated nurses, a uniform nationwide informatics system, and the support of VHA administration and managerial staff.

Background: The National Veterans Affairs Surgical Risk Study was designed to collect reliable, valid data on patient risk and outcomes for major surgery in the Veterans Health Administration and to report comparative risk-adjusted postoperative mortality and morbidity rates for surgical services in the Veterans Health Administration., Study Design: This was a cohort study conducted at 44 Veterans Affairs Medical Centers closely affiliated with university medical centers. Included were 87,078 major noncardiac operations performed under general, spinal, or epidural anesthesia between October 1, 1991, and December 31, 1993. The main outcomes measures in this report are 21 postoperative adverse events (morbidities) occurring within 30 days after the index procedure. Multivariable logistic regression risk-adjustment models for all operations and for eight surgical subspecialties were developed., Results: Patient risk factors predictive of postoperative morbidity included serum albumin level, American Society of Anesthesia class, the complexity of the operation, and 17 other preoperative risk variables. Wide variation in the unadjusted rates of one or more postoperative morbidities for all operations was observed across the 44 hospitals (7.4-28.4%). Risk-adjusted observed-to-expected ratios ranged from 0.49 to 1.46. The Spearman rank order correlation between the ranking of the hospitals based on unadjusted morbidity rates and risk-adjusted observed-to-expected ratios for all operations was 0.87. There was little or no correlation between the rank order of the hospitals by risk-adjusted morbidity and risk-adjusted mortality., Conclusions: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of postoperative mortality and morbidity rates after major noncardiac operations. Risk adjustment had only a modest effect on the rank order of the hospitals.

Background: The National Veterans Affairs Surgical Risk Study was designed to collect reliable, valid data on patient risk and outcomes for major surgery in the Veterans Health Administration and to report comparative risk-adjusted postoperative mortality rates for surgical services in Veterans Health Administration., Study Design: This cohort study was conducted in 44 Veterans Affairs Medical Centers. Included were 87,078 major noncardiac operations performed under general, spinal, or epidural anesthesia between October 1, 1991, and December 31, 1993. The main outcomes measure was all-cause mortality within 30 days after the index procedure. Multivariable logistic regression risk-adjustment models for all operations and for eight surgical subspecialties were developed. Risk-adjusted surgical mortality rates were expressed as observed-to-expected ratios and were compared with unadjusted 30-day postoperative mortality rates., Results: Patient risk factors predictive of postoperative mortality included serum albumin level, American Society of Anesthesia class, emergency operation, and 31 additional preoperative variables. Considerable variability in unadjusted mortality rates for all operations was observed across the 44 hospitals (1.2-5.4%). After risk adjustment, observed-to-expected ratios ranged from 0.49 to 1.53. Rank order correlation of the hospitals by unadjusted and risk-adjusted mortality rates for all operations was 0.64. Ninety-three percent of the hospitals changed rank after risk adjustment, 50% by more than 5 and 25% by more than 10., Conclusions: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of risk-adjusted postoperative mortality rates after major noncardiac operations. Risk adjustment had an appreciable impact on the rank ordering of the hospitals and provided a means for monitoring and potentially improving the quality of surgical care.

BACKGROUND: The Zollinger-Ellison syndrome, implicating a gastrinoma, was first recognized as a disease entity in 1955. At that time, total gastrectomy was the most common treatment approach. Advances in several aspects of the disease have occurred since that time. METHODS: The authors reviewed the changes that have developed since 1955 in the diagnosis, imaging studies, operative and nonoperative management, and follow-up of patients with this disease. RESULTS: The presence of a gastrinoma can be confirmed by a secretin stimulation test. A variable number of patients have hyperparathyroidism as part of the multiple endocrine neoplasm syndrome type 1 (MEN 1). Localization of the primary gastrinoma has been assisted by selective angiography, endoscopic ultrasonography, and the octreotide scan. H2-blockers or omeprazole, sometimes at high doses, usually controls acid secretion. Surgical removal of the primary gastrinoma is performed when feasible, and parathyroidectomy is indicated in those patients with hyperparathyroidism in the MEN 1 syndrome. Follow-up is facilitated by measurement of fasting serum gastrin levels. CONCLUSIONS: Several innovations have improved our capability to diagnose and effectively manage patients with gastrinoma.

The advent of healthcare reform and the rapid application of new technologies have resulted in a paradigm shift in medical practice. Integrating medical Informatics into the full spectrum of medical education is a viral step toward implementing this new instructional model, a step required for the understanding and practice of modern medicine. We have developed an informatics curriculum, a new educational paradigm, and an intranet-based teaching module which are designed to enhance adult-learning principles, life-long self education, and evidence-based critical thinking. Thirty two, fourth year medical students have participated in a one month, full time, independent study focused on but not limited to four topics: mastering the windows-based environment, understanding hospital based information management systems, developing competence in using the internet/intranet and world wide web/HTML, and experiencing distance communication and TeleVideo networks. Each student has completed a clinically relevant independent study project utilizing technology mastered during the course. This initial curriculum offering was developed in conjunction with faculty from the College of Medicine, College of Engineering, College of Education, College of Business, College of Public Health. Florida Center of Instructional Technology, James A. Haley Veterans Hospital, Moffitt Cancer Center, Tampa General Hospital, GTE, Westshore Walk-in Clinic (paperless office), and the Florida Engineering Education Delivery System. Our second step toward the distributive integration process was the introduction of Medical Informatics to first, second and third year medical students. To date, these efforts have focused on undergraduate medical education. Our next step is to offer workshops in Informatics to college of medicine faculty, to residents in post graduate training programs (GME), and ultimately as a method of distance learning in continuing medical education (CME).

Background: The signal transduction pathways important in regulating the growth and differentiation of malignant cells are poorly understood. Recent evidence has implicated activation of the protein kinase C (PKC) family of signaling proteins in pancreatic carcinoma during cytokine-induced cytostasis and differentiation., Methods: A human pancreatic adenocarcinoma (HPAC) cell line was exposed to tumor necrosis factor-alpha (TNF-alpha; 40 ng/ml) for 6 days. Cytostasis and viability were confirmed by daily MTT [(3(4,5)-dimethyl-thiazol-2-yl) 2,5-diphenyl-tetrazolium bromide] and trypan exclusion assay. Protein fractions were isolated daily and subjected to immunoblot analysis for the normal (terminally differentiated) pancreatic ductal cell marker carbonic anhydrase II (CA II) as well as specific PKC isoforms (alpha, beta, gamma, eta, and zeta)., Results: Growth arrest occurred in HPAC cells after exposure to TNF-alpha for 48 h, with viability maintained above 90% throughout the 6-day time course. CA II immunoreactivity was not detected in untreated controls but appeared after 2 days of TNF-alpha exposure, peaking on day 6. Concurrently, TNF-alpha induced the selective downregulation of PKC-alpha, whereas PKC-gamma levels increased. PKC-beta and PKC-eta immunoreactivity did not change. The atypical PKC-zeta isoform developed a doublet banding pattern in response to TNF-alpha, although overall PKC-zeta levels did not change., Conclusions: TNF-alpha-induced growth arrest and differentiation in HPAC cells is associated with the selective downregulation of PKC-alpha and upregulation of PKC-gamma.

With the advent of transjugular intrahepatic porta-systemic stent shunt and the wider application of the surgically placed small diameter prosthetic H-graft portacaval shunt (HGPCS), partial portal decompression in the treatment of portal hypertension has received increased attention. The clinical results supporting the use of partial portal decompression are its low incidence of variceal rehemorrhage due to decreased portal pressures and its low rate of hepatic failure, possibly due to maintenance of blood flow to the liver. Surprisingly, nothing is known about changes in portal hemodynamics and effective hepatic blood flow following partial portal decompression. To prospectively evaluate changes in portal hemodynamics and effective hepatic blood flow brought about by partial portal decompression, the following were determined in seven patients undergoing HGPCS: intraoperative pre- and postshunt portal vein pressures and portal vein-inferior vena cava pressure gradients, intraoperative pre- and postshunt portal vein flow, and pre- and postoperative effective hepatic blood flow. With HGPCS, portal vein pressures and portal vein-inferior vena cava pressure gradients decreased significantly, although portal pressures remained above normal. In contrast to the significant decreases in portal pressures, portal vein blood flow and effective hepatic blood flow do not decrease significantly. Changes in portal vein pressures and portal vein-inferior vena cava pressure gradients are great when compared to changes in portal vein flow and effective hepatic blood flow. Reduction of portal hypertension with concomitant maintenance of hepatic blood flow may explain why hepatic dysfunction is avoided following partial portal decompression.

Hepatic dysfunction is a major contributor to death in multiple organ system failure. To evaluate whether this dysfunction increases with the length of sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid peroxidation in rat livers. Livers were harvested at 18, 21, 24, and 27 hr, homogenized, and microsomal fractions prepared. Cytochrome P450 concentration was determined by assay and P450 activity was determined by the metabolism of ethoxyresorufin and ethoxycoumarin. Lipid peroxidation was estimated by measuring malondialdehyde content. Septic rats showed decreases in P450 levels and activity, which worsened with duration of sepsis. These decreases were partially lessened by hyperoxia. Although there was a trend toward increased lipid peroxidation, this effect was not statistically significant. This study suggests that while MFO content and activity decrease with sepsis, these decreases do not appear to be related to the production of oxygen-derived free radicals. Furthermore, hyperoxia actually appears to have a protective role in this instance.

Background: Fulminant acute pancreatitis is a disease of complex origin that results in activation of several of the proinflammatory cytokines. Because interleukin-1 (IL-1) is an integral early component of the acute inflammatory process, the use of an IL-1 receptor antagonist (IL-1ra) was investigated in experimental acute pancreatitis to determine the therapeutic potential of proximal cytokine blockade and to further establish the role of inflammatory cytokines in the pathogenesis of acute pancreatitis., Methods: IL-1ra was administered in escalating doses either before or after acute edematous, necrotizing pancreatitis was induced in adult male mice by injection of cerulein. The severity of pancreatitis was quantified by serum amylase, lipase, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels, pancreatic wet weight, and blinded histologic grading., Results: Administration of medium (10 mg/kg) and high (100 mg/kg) doses of IL-1ra either before or after the induction of pancreatitis significantly decreased the expected rise in pancreatic wet weight, lipase, IL-6, and TNF-alpha (all, p < 0.01). Serum amylase was significantly reduced when IL-1ra was administered in either dosage before (p < 0.05), but not after, induction of pancreatitis. Pancreatic edema, necrosis, and inflammatory cell infiltrate were significantly diminished (p < 0.05) by histologic grading in all animals receiving medium or high doses of IL-1ra. Low doses of IL-1ra (1.0 mg/kg) had modest effects if given before, but no effect if given after, induction of pancreatitis., Conclusions: The proinflammatory cytokines IL-6 and TNF-alpha are elevated during experimental acute pancreatitis and correlate well with the severity of local pancreatic destruction. Blockade of the cytokine cascade at the level of the IL-1 receptor before or soon after induction of pancreatitis significantly attenuates the rise in these cytokines and is associated with decreased severity of pancreatitis and reduced intrinsic pancreatic damage.

Objective: This study determined the ability of interleukin-1 receptor antagonist (IL-1ra) to decrease the mortality of experimental acute pancreatitis. The response of the inflammatory cytokine cascade and its subsequent effects on pancreatic morphology were measured to determine the role of these peptides in mediating pancreatic injury., Summary Background Data: Previous studies have shown that proinflammatory cytokines are produced in large amounts during acute pancreatitis and that blockade at the level of the IL-1 receptor significantly decreases intrinsic pancreatic damage. The subsequent effect on survival is not known., Methods: A lethal form of acute hemorrhagic necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented (CDE) diet for 72 hours. For determination of mortality, the animals were divided into 3 groups of 45 animals each: control subjects received 100/microL normal saline intraperitoneally every 6 hours for 5 days; IL-1ra early mice received recombinant interleukin-1 receptor antagonist 15 mg/kg intraperitoneally every 6 hours for 5 days beginning at time 0; IL-1ra late mice received IL-1ra 15 mg/kg intraperitoneally every 6 hours for 3.5 days beginning 1.5 days after introduction of the CDE diet. A parallel experiment was conducted simultaneously with a minimum of 29 animals per group, which were sacrificed daily for comparisons of serum amylase, lipase, IL-1, IL-6, tumor necrosis factor-alpha, IL-1ra, pancreatic wet weight, and blind histopathologic grading., Results: The 10-day mortality in the untreated control group was 73%. Early and late IL-1ra administration resulted in decreases of mortality to 44% and 51%, respectively (both p < 0.001). Interleukin-1 antagonism also was associated with a significant attenuation in the rise in pancreatic wet weight and serum amylase and lipase in both early and late IL-1ra groups (all p < 0.05). All control animals developed a rapid elevation of the inflammatory cytokines, with maximal levels reached on day 3. The IL-1ra-treated animals, however, demonstrated a blunted rise of these mediators (all p < 0.05). Blind histologic grading revealed an overall decrease in the severity of pancreatitis in those animals receiving the antagonist., Conclusions: Early or late blockade of the cytokine cascade at the level of the IL-1 receptor significantly decreases the mortality of severe acute pancreatitis. The mechanism by which this is accomplished appears to include attenuation of systemic inflammatory cytokines and decreased pancreatic destruction.

Background: As the population ages, more elderly individuals will be at risk for the development of gastrointestinal malignancies traditionally treated with radical operation. In the past, many major cancer operations were reserved for patients < 65 or 70 years of age, but as the life expectancy for a 70-year-old has improved, this policy has been questioned., Methods: We examined the records of 124 consecutive patients who underwent one of three major operations (esophagogastrectomy, major liver resection, pancreatoduodenectomy) for gastrointestinal cancer during the past 6 years to determine if preoperative risk factors, operative mortality, length of stay, length of procedure, estimated blood loss, rate of major complication, or Kaplan-Meier survival was different for patients > or = 70 years of age as compared with younger patients., Results: For patients at our institution undergoing esophagogastrectomy, major liver resection, or pancreatoduodenectomy, we found no significant difference in any of the parameters measured. There was no significant difference in any parameter when comparing patients > or = 70 versus < 70 years of age., Conclusions: We conclude that patients > or = 70 years of age are not necessarily less suitable candidates for major cancer operations than are those < 70 years of age if other risk factors are acceptable. Elderly patients should be included in clinical trials.

Background: It has become common for fourth-year medical students interested in surgical careers to leave their parent university to take extramural elective rotations in surgery at other institutions. These "audition extramurals," while of some educational value, are often repetitions of prior clerkships and may not broaden the student's educational horizons. Instead, they are intended to enhance a student's competitiveness in the match. While recent opinions and questionnaires have suggested that such extramural rotations are not valuable in general surgery, no study has formally evaluated the effect of extramural electives on the residency match., Methods: Over a 6-year period, the authors reviewed the outcome in 99 students who took extramural elective rotations in surgery. Of the 99 students, 28 were from the authors' institution who left to do extramural rotations elsewhere and 71 were outside students who came to the University of South Florida for an elective. While the elective rotation increased the probability of an interview, it did not alter ranking or probability of matching., Results: For general surgery students, the elective rotation may actually decrease competitiveness, while for specialty students, it appears necessary but not sufficient to improve match outcome. The elective might facilitate placement for students who did not match, but did not do so predictably., Conclusions: The authors conclude that extramural elective rotations should be taken for educational value only and not as auditions for residency.

The early diagnosis of acute appendicitis before progression to gangrene or abscess formation is recognized as important to minimize morbidity from this common disease process. As our population ages, the challenge for expedient diagnosis and intervention in older age groups will become more significant. Prompted by recent unexpected complications occurring in elderly patients, we reviewed 100 consecutive admissions with the diagnosis of appendicitis to a tertiary Veterans Administration hospital. All patients were males and were arbitrarily divided into three age groups: less than 50, 50-70, and greater than 70 years of age. There were no patients less than 20 years old. Operative findings were classified as simple acute appendicitis, ruptured or perforated appendicitis, appendicitis associated with intra-abdominal abscess, and finally other when the operative diagnosis differed from appendicitis. Of the 37 patients less than 50 years of age, 28 were found to have simple acute appendicitis, making this by far the most common finding in this age group (P < 0.05). Only two of the 18 patients aged 50-70 with appendicitis demonstrated simple acute appendicitis, with the remainder having progressed to perforation or abscess formation (P < 0.05). Patients greater than 70 years of age were significantly more likely than any other age group to manifest appendicitis associated with intra-abdominal abscess (10 of 19, P < 0.05). Eight patients died in this series, six of whom were more than 70 years of age. In most cases, mortality was directly attributable to infectious complications of perforated appendicitis. There were no deaths in the under 50 age group.(ABSTRACT TRUNCATED AT 250 WORDS)

TNF is a 17kD cytokine classically known for its cytotoxic effects on malignant cells. More recent cell culture studies demonstrated TNF induced cytostasis associated with the expression of a terminally differentiated phenotype. This was best characterized in malignant hematopoietic models, although a similar action on cells derived from solid tumors is now increasingly recognized. In the present study, six day exposure to TNF (40 ng/ml) stimulated morphologic changes in a human pancreatic adenocarcinoma cell line (HPAC), including increased cellular homogeneity, decreased nuclear to cytoplasmic ratio and detachment from the cell monolayer. Proliferation and DNA synthesis were reversibly inhibited while cellular viability was maintained. Parallel to the changes in morphology and growth was the delayed appearance of carbonic anhydrase II (CA II, E.C. 4.2.1.1), an accepted marker for pancreatic cells of ductal origin. A concomitant increase in the steady-state level of CA II mRNA was also observed over the time-course of TNF exposure. These results suggest a novel role for TNF in the induction of a more terminally differentiated ductal cell phenotype in a human pancreatic carcinoma model.

The presence of ANP prohormone immunoreactivity in rat GI tract suggests that it may be an extracardiac site of ANP synthesis. The aim of this study was to investigate the expression of ANP mRNA in the adult rat GI tract. ANP mRNA was detected by ribonuclease protection analysis in stomach, small and large intestines, and rectum/anus. The highest concentrations of ANP transcripts were found in the proximal stomach, antrum, proximal colon, and rectum/anus at levels that ranged from 1 to 10% of that found in cardiac ventricle. Northern blot analysis of total RNA from these tissues identified a single 0.9 kb ANP transcript similar to that detected in heart. Gel filtration chromatography of tissue extracts provided evidence for the presence of the complete ANP prohormone in proximal stomach, antrum, proximal colon and rectum/anus. These results demonstrate that the gene for ANP is expressed in specific regions of the rat GI tract, suggesting that tissue-specific differential regulation of ANP synthesis occurs within the GI tract.

Several peptide hormones have been shown to influence growth and function in pancreatic carcinoma and have given evidence for an autocrine feedback loop governing the proliferation of these malignant cells. Conversely, steroid hormones including glucocorticoids have been shown to inhibit the growth of pancreatic cancer cells; however, the prevalence of the glucocorticoid receptor or its mechanism of growth suppression in these tumors is unknown. The ability of growth factors thought to be active in this autocrine loop to reverse the glucocorticoid-induced growth inhibition was studied in vitro in a human pancreatic adenocarcinoma (HPAC) cell line with a well-characterized glucocorticoid receptor (GR). The glucocorticoid dexamethasone (DEX) inhibited growth in a dose-dependent manner as measured by a [3H]thymidine incorporation assay as well as an MTT cell proliferation assay. Maximal effects were seen within 48 hr at a concentration of 100 nM DEX, suppressing growth to approximately 18% of control. When the maximally suppressed DEX-treated cells were exposed to exogenous growth factors, they rapidly attained or exceeded the growth rate of control cells: insulin-like growth factor = 106%, transforming growth factor-alpha = 134%, insulin = 151%, and epidermal growth factor = 187% (all P < 0.05, Student's t test). In order to determine the frequency of the GR in pancreatic cancer and the clinical relevance of our findings, immunohistochemical staining for the GR was performed on 20 human tumors. Twelve (60%) of all cancers, as well as all normal pancreatic tissues (n = 4), stained positively for cytoplasmic and/or nuclear GR with expression correlating highly with degree of tumor differentiation (Kruskal-Wallis test, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The management of cancer in the older person is an increasingly common aspect of oncologic practice. The central questions concern effectiveness and safety of antineoplastic therapy, clinical criteria to identify patients who may benefit from treatment, and individualized management plans. To address these questions, we review the influence of age on various forms of cancer treatment, explore the basis of treatment-related decisions in older persons with cancer, and propose areas for future investigation. Age itself is not a contraindication to cancer treatment. Individualized treatment plans, based on appropriate diagnosis, staging and comprehensive geriatric assessment, are most beneficial to the older patients.

A new human pancreatic cancer (HPAC) cell line was established from a nude mouse xenograft (CAP) of a primary human pancreatic ductal adenocarcinoma. In culture, HPAC cells form monolayers of morphologically heterogenous, polar epithelial cells, which synthesize carcinoembryonic antigen, CA 19-9, CA-125, cytokeratins, antigens for DU-PAN-2, HMFG1, and AUA1, but do not express chromogranin A or vimentin indicative of their pancreatic ductal epithelial cell character. In the presence of serum, HPAC cell DNA synthesis was stimulated by insulin, insulin growth factor-I, epidermal growth factor, and TGF-α but inhibited by physiologic concentrations of hydrocortisone and dexamethasone. Dose-dependent inhibition of DNA synthesis was limited to steroids with glucocorticoid activity. The inhibitory effect of dexamethasone was abolished by the glucocorticoid antagonist RU 384862 Binding of [3H] dexamethasone to cytosolic proteins was specific and saturable at 4 degrees C. Scatchard analysis of binding data demonstrated a single class of high-affinity binding sites (K(d) = 3.8 ± 0.9 nM; B(max) = 523 ± 128 fmol/mg protein). Western blot analysis revealed a major protein band that migrated at a M(r) of 96 kDa. Northern blot analysis identified an mRNA of approximately 7 kilobases which hybridized with a specific glucocorticoid receptor complementary-DNA probe (OB7). These findings support a role for glucocorticoids in the regulation of human malignant pancreatic cell function.