Two consecutive partial liver transplants in a patient with Classic Maple Syrup Urine Disease.

Maple syrup urine disease is caused by a deficiency in the branched chain ketoacid dehydrogenase (BCKAD) complex. This results in the accumulation of branched chain amino acids (BCAA) and branched chain ketoacids in the body. Even when aggressively treated with dietary restriction of BCAA, patients experience long term cognitive, neurological and psychosocial problems. Liver transplantation from deceased donors has been shown to be an effective modality in introducing adequate BCKAD activity, attaining a metabolic cure for patients. Here, we report the clinical course of the first known patient with classic MSUD who received two consecutive partial liver grafts from two different living non-carrier donors and his five year outcome posttransplant. We also show that despite the failure of the first liver graft, and initial acute cellular rejection of the second liver graft in our patient, his metabolic control remained good without metabolic decompensation.

Effect of pH on high-temperature production of bacterial penicillin acylase in Escherichia coli.

High-temperature-oriented production of bacterial penicillin acylase (PAC), which is usually expressed at low temperatures (less than 30 degrees C), was demonstrated in this study via heterologous expression of the Providencia rettgeri (P. rettgeri) pac gene in Escherichia coli (E. coli). While it is possible to produce PAC at a temperature as high as 37 degrees C, the environmental condition (specifically, culture pH) critically affected culture performance. Production of PAC at 37 degrees C was feasible only when culture pH was close to neutral (i.e., 6.5-7.5). Outside this pH range, cell physiology for the host/vector system was seriously affected, resulting in poor culture performance. In acidic culture environments, temperature significantly affected the pac expression level and specific PAC activity decreased with an increase in culture temperature. In basic culture environments, cell growth was seriously inhibited though the pac expression level was minimally affected by temperature. Such unusual types of pH and temperature effects on pac expression were never reported for bacterial PACs. The results suggest that culture pH should be precisely controlled for the current host/vector systems being applied on the overproduction of P. rettgeri PAC in E. coli at high temperatures.

Photoaffinity labeling of insect nicotinic acetylcholine receptors with a novel [(3)H]azidoneonicotinoid.

The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel in the insect CNS and a target for major insecticides. Here we use photoaffinity labeling to approach the functional architecture of insect nAChRs. Two candidate 5-azido-6-chloropyridin-3-yl photoaffinity probes are evaluated for their receptor potencies: azidoneonicotinoid (AzNN) with an acyclic nitroguanidine moiety; azidodehydrothiacloprid. Compared to their non-azido parents, both probes are of decreased potencies at Drosophila (fruit fly) and Musca (housefly) receptors but AzNN retains full potency at the Myzus (aphid) receptor. [(3)H]AzNN was therefore radiosynthesized at high specific activity (84 Ci/mmol) as a novel photoaffinity probe. [(3)H]AzNN binds to a single high-affinity site in Myzus that is competitively inhibited by imidacloprid and nicotine and further characterized as to its pharmacological profile with various nicotinic ligands. [(3)H]AzNN photoaffinity labeling of Myzus and Homalodisca (leafhopper) detects a single radiolabeled peak in each case displaceable with imidacloprid and nicotine and with molecular masses corresponding to approximately 45 and approximately 56 kDa, respectively. The photoaffinity-labeled receptor in both Drosophila and Musca has imidacloprid- and nicotine-sensitive profiles and migrates at approximately 66 kDa. These photoaffinity-labeled polypeptides are considered to be the insecticide-binding subunits of native insect nAChRs.

Embedding guidelines into direct physician order entry: simple methods, powerful results.

Kaiser Permanente in the Northwest Region has implemented a comprehensive outpatient computer-based patient record (CPR). Using this system, clinicians electronically order laboratory tests, radiology tests, and prescriptions. Clinicians also use this comprehensive CPR to document encounters, code diagnoses and procedures, maintain problem lists, and to send patient-specific messages and referrals to other medical providers. Healthcare for our entire membership of 440,000 covered lives is now provided through this system [1]. Implementation of a comprehensive CPR with direct physician order-entry provides the opportunity to embed guidelines into the ordering process. This article describes the underlying theme and various simple but effective methods we use to embed guidelines into the ordering process. Our experience demonstrates the powerful effect of these simple methods to reduce unnecessary variation and to reduce cost while maintaining or improving the quality of care delivery.

Successful implementation of a comprehensive computer-based patient record system in Kaiser Permanente Northwest: strategy and experience.

Kaiser Permanente Northwest (KPNW) has implemented a computer-based patient record (CPR) system for outpatients. Clinicians at KPNW use this comprehensive CPR to electronically document patient encounters; code diagnoses and procedures; maintain problem lists; order laboratory tests, radiology tests, and prescriptions; and send patient-specific messages and referrals to other medical providers. More than 700 clinicians, representing more than 20 medical and surgical specialties, and 2600 support staff in 31 geographically separate sites use this system as the information foundation of delivery and documentation of health care for KPNW's membership of 430,000. As of May 1998, more than four million visits and two million telephone calls had been processed and documented into the system. More than 5000 outpatient visits are processed and documented each weekday. From an integrated clinical workstation, clinicians also access e-mail, an extensive results-reporting system, and sites on both the internet and KPNW's intranet. This article describes a strategy for and experience with the implementation of a large-scale, comprehensive CPR in an integrated HMO. This information may be useful for persons attempting to implement CPRs in their own institutions.

The effects of an Electronic Medical Record on patient care: clinician attitudes in a large HMO.

OBJECTIVE: The purpose of this study is to examine the attitudes of clinicians in a large HMO toward the effect of an outpatient Electronic Medical Record system on the quality of patient care. Attitudes toward a Results Reporting system and an online charting and ordering system are also compared. DESIGN: A cross-sectional study was performed using a survey of Kaiser Permanente Northwest clinicians. In addition, interviews were conducted with the physician leaders of the clinical departments at Kaiser Permanente Northwest. MEASUREMENTS: Clinician attitudes are measured regarding the effects of a Results Reporting system and an online charting and ordering system on the overall quality of patient care and other care-related indices. RESULTS: Most clinicians feel that the outpatient Electronic Medical Record has improved the overall quality of patient care, with 72% reporting an improvement with the use of the Results Reporting system, and 60% reporting an improvement with the use of the online charting and ordering system. On average, clinicians feel that the EMR has also improved the quality of the patient-clinician interaction, the ability to coordinate the care of patients with other departments, the ability to detect medication errors, the timeliness of referrals, and the ability to act on test results in a timely fashion. CONCLUSION: Clinicians perceive an improvement in patient care as a result of using an outpatient Electronic Medical Record system. Clinicians have higher opinions, however, of the effects of a Results Reporting system compared to an online charting and ordering system.

Implementation of a comprehensive computer-based patient record system in Kaiser Permanente's Northwest Region.

Kaiser Permanente, Northwest Region, has implemented a comprehensive outpatient computer-based patient record. Clinicians use this system to document encounters, code diagnoses and procedures, maintain problem lists, order laboratory and radiology tests, and send prescriptions electronically. Clinicians also use it to send patient-specific messages and referrals between medical providers. More than 300 primary care clinicians in 10 separate clinics are now using the system in the delivery of care. This article describes our strategy and experience in the implementation of a comprehensive computer-based patient record.

Evaluating a comprehensive outpatient clinical information system: a case study and model for system evaluation.

Decisions about information system implementation are often justified through a cost-benefit analysis. The ability to improve efficiency and outcomes while decreasing costs through information systems--by allowing for multiple and instant simultaneous access to information, through data monitoring and altering, through automation of protocols, and by collecting information for population-based health care as opposed to individual illness-care--are all potential benefits of a comprehensive clinical information system. Measuring the quantitative impact of these system improvements, however, is difficult. Doing a complete cost-benefit analysis of a comprehensive clinical information system is unrealistic due to the many assumptions necessary and the multiple confounding factors that are involved. In our Clinical Information Systems deployment in Kaiser Permanente, Northwest Region, we have elected not to do a detailed cost-benefit analysis. Instead, we have done an evaluation, based on success criteria, of a pilot implementation of a vendor-supplied system. This evaluation is based on clinician acceptance, system usage, technical factors, and quantitative effects on physician productivity. We also considered qualitative factors such as relationship with and responsiveness of the system vendor. We are moving ahead to regionalize this clinical information system based on such an evaluation of our pilot project. This paper outlines the approach that we have taken in evaluating our implementation of this system. It may provide some guidance for organizations on how to make a decision about whether or not to regionalize a clinical information system based on the evaluation of a pilot-site implementation.

Silent ischemia after coronary angioplasty: evaluation of restenosis and extent of ischemia in asymptomatic patients by tomographic thallium-201 exercise imaging and comparison with symptomatic patients.

One hundred sixteen patients were evaluated to determine the ability of single photon emission computed tomographic (SPECT) thallium-201 exercise and redistribution imaging to detect silent ischemia secondary to restenosis in asymptomatic patients after single and multiple vessel percutaneous transluminal coronary angioplasty and the findings were compared with SPECT imaging detection of restenosis in symptomatic patients. The value of exercise electrocardiography (ECG) and the amount of ischemic myocardium in symptomatic and asymptomatic patients were determined. Forty-one patients were asymptomatic after angioplasty; 77% of these had chest pain before angioplasty. Seventy-five patients had chest pain after angioplasty; 99% of these had chest pain before angioplasty. Restenosis occurred in 61% of asymptomatic and 59% of symptomatic patients and in 46% of the vessels in both asymptomatic and symptomatic patients. Sensitivity, specificity and accuracy for detection of restenosis by SPECT in individual patients were 96%, 75% and 88% versus 91%, 77% and 85%, respectively, in the asymptomatic versus symptomatic groups (p = NS). Sensitivity, specificity and accuracy for restenosis detection in individual vessels were 90%, 89% and 89% versus 84%, 77% and 84%, respectively, in the asymptomatic and symptomatic groups (p = NS), with similar results for the three major arteries. Sensitivity and accuracy of exercise ECG were significantly less than those of SPECT imaging for the patients with silent (40% and 44%) and symptomatic (59% and 64%) ischemia (p less than 0.001). Restenosis of vessels in the patients with silent and symptomatic ischemia was associated with an equal amount and degree of severity of ischemic myocardium in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-based tutoring from a medical knowledge base.

The past decade has seen the emergence of programs that make use of large knowledge bases to assist physicians in diagnosis within the general field of internal medicine. One such program, Internist-I, contains knowledge about over 600 diseases, covering a significant proportion of internal medicine. This paper describes the process of converting a subset of this knowledge base--in the area of cardiovascular diseases--into a probabilistic format, and the use of this resulting knowledge base to teach medical diagnostic knowledge. The system (called KBSimulator--for Knowledge-Based patient Simulator) generates simulated patient cases and uses these cases as a focal point from which to teach medical knowledge. This project demonstrates the feasibility of building an intelligent, flexible instructional system that uses a knowledge base constructed primarily for medical diagnosis.