Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver.

Acute intermittent porphyria (AIP) is an autosomal-dominant hepatic disorder caused by the half-normal activity of hydroxymethylbilane (HMB) synthase. Symptomatic individuals experience life-threatening acute neurovisceral attacks that are precipitated by factors that induce the hepatic expression of 5-aminolevulinic acid synthase 1 (ALAS1), resulting in the marked accumulation of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Here, we provide the first detailed description of the biochemical and pathologic alterations in the explanted liver of an AIP patient who underwent orthotopic liver transplantation (OLT) due to untreatable and debilitating chronic attacks. After OLT, the recipient's plasma and urinary ALA and PBG rapidly normalized, and her attacks immediately stopped. In the explanted liver, (a) ALAS1 mRNA and activity were elevated approximately ~3- and 5-fold, and ALA and PBG concentrations were increased ~3- and 1,760-fold, respectively; (b) uroporphyrin III concentration was elevated; (c) microsomal heme content was sufficient, and representative cytochrome P450 activities were essentially normal; (d) HMB synthase activity was approximately half-normal (~42%); (e) iron concentration was slightly elevated; and (f) heme oxygenase I mRNA was increased approximately three-fold. Notable pathologic findings included nodular regenerative hyperplasia, previously not reported in AIP livers, and minimal iron deposition, despite the large number of hemin infusions received before OLT. These findings suggest that the neurovisceral symptoms of AIP are not associated with generalized hepatic heme deficiency and support the neurotoxicity of ALA and/or PBG. Additionally, they indicate that substrate inhibition of hepatic HMB synthase activity by PBG is not a pathogenic mechanism in acute attacks.

Hospitalists' ability to use hand-carried ultrasound for central venous pressure estimation after a brief training intervention: a pilot study.

BACKGROUND: Access to hand-carried ultrasound technology for noncardiologists has increased significantly, yet development and evaluation of training programs are limited. OBJECTIVE: We studied a focused program to teach hospitalists image acquisition of inferior vena cava (IVC) diameter and IVC collapsibility index with interpretation of estimated central venous pressure (CVP). METHODS: Ten hospitalists completed an online educational module prior to attending a 1-day in-person training session that included directly supervised IVC imaging on volunteer subjects. In addition to making quantitative assessments, hospitalists were also asked to visually assess whether the IVC collapsed more than 50% during rapid inspiration or a sniff maneuver. Skills in image acquisition and interpretation were assessed immediately after training on volunteer patients and prerecorded images, and again on volunteer patients at least 6 weeks later. RESULTS: Eight of 10 hospitalists acquired adequate IVC images and interpreted them correctly on 5 of the 5 volunteer subjects and interpreted all 10 prerecorded images correctly at the end of the 1-day training session. At 7.4 ± 0.7 weeks (range, 6.9-8.6 weeks) follow-up, 9 of 10 hospitalists accurately acquired and interpreted all IVC images in 5 of 5 volunteers. Hospitalists were also able to accurately determine whether the IVC collapsibility index was more than 50% by visual assessment in 180 of 198 attempts (91% of the time). CONCLUSIONS: After a brief training program, hospitalists acquired adequate skills to perform and interpret hand-carried ultrasound IVC images and retained these skills in the near term. Though calculation of the IVC collapsibility index is more accurate, coupling a qualitative assessment with the IVC maximum diameter measurement may be acceptable in aiding bedside estimation of CVP.

Prevalence of asymptomatic left ventricular systolic dysfunction in at-risk medical inpatients.

BACKGROUND: Asymptomatic left ventricular systolic dysfunction is an important risk factor for heart failure and death. Given the availability of patients, trained personnel, and equipment, the hospital is an ideal setting to identify and initiate treatment for left ventricular systolic dysfunction. The purpose of this study was to determine the prevalence of asymptomatic left ventricular systolic dysfunction in patients 45 years of age or older with at least one clinical heart failure risk factor admitted to a general medical service. METHODS: Bedside, hand-carried echocardiography provided quantitative assessment of left ventricular systolic function in 217 medical inpatients 45 years of age or older who had at least one heart failure risk factor. Patients with known or suspected heart failure or with an assessment of left ventricular function in the past 5 years were excluded. We measured the prevalence of asymptomatic left ventricular systolic dysfunction, defined by left ventricular ejection fraction of 50% or lower, and its association with heart failure risk factors. RESULTS: Of 207 patients with interpretable images, 11 (5.3%) had a left ventricular ejection fraction of 50% or lower. Patients with left ventricular systolic dysfunction had more heart failure risk factors than those without left ventricular systolic dysfunction (3.09±0.8 vs 2.5±1.0, P=.04). The total number of heart failure risk factors trended towards an association with a greater prevalence of asymptomatic left ventricular systolic dysfunction, but this did not reach significance (odds ratio 1.74; 95% confidence interval, 0.97-3.12, P=.06). CONCLUSIONS: Asymptomatic left ventricular systolic dysfunction is present in about 1 of every 20 general medical inpatients with at least one risk factor for heart failure. Because treatment of asymptomatic left ventricular systolic dysfunction may reduce morbidity, further studies examining the costs and benefits of using hand-carried ultrasound to identify this important condition in general medical inpatients are warranted.

Buprenorphine maintenance treatment in a primary care setting: outcomes at 1 year.

The purposes of this study were to assess outcomes of patients prescribed buprenorphine at a primary care practice and to identify factors associated with favorable outcomes. All 255 patients given at least one prescription for buprenorphine between August 2003 and September 1, 2007, at a primary care practice in Baltimore were included. Data regarding demographics and comorbidities were collected retrospectively. Patients were classified as "opioid-positive" or "opioid-negative" each month based on patient report, urine toxicology, and provider assessment. After 12 months, 145 (56.9%) patients remained in treatment, and 64.7% of their months were opioid-negative. Patients using heroin were less likely to be opioid-negative, whereas those using prescription opioids were more likely to be opioid-negative. Polysubstance use was associated with increased treatment retention. The prescription of buprenorphine for opioid dependence treatment can be incorporated into primary care practice, and many patients, including polysubstance users, benefit from this treatment.

Hand-carried ultrasound performed by hospitalists: does it improve the cardiac physical examination?

OBJECTIVE: The traditional physical examination of the heart is relatively inaccurate. There is little information regarding whether cardiac hand-carried ultrasound performed by noncardiologists adds to the accuracy of physical examinations. The purpose of this study was to determine whether hand-carried ultrasound can add to the accuracy of hospitalists' cardiac physical examinations. METHODS: During a focused training program in hand-carried echocardiography, 10 hospitalists performed cardiac examinations of 354 general medical inpatients first by physical examination and then by hand-carried ultrasound. Eligible inpatients included those for whom a conventional hospital echocardiogram was ordered. We measured how frequently the hospitalists' cardiac examination with or without hand-carried ultrasound matched or came within 1 scale level of an expert cardiologist's interpretation of the hospital echocardiogram. RESULTS: Adding hand-carried ultrasound to the physical examination improved hospitalists' assessment of left ventricular function, cardiomegaly, and pericardial effusion. For left ventricular function, using hand-carried ultrasound increased the percentage of exact matches with the expert cardiologist's assessment from 46% to 59% (P=.005) and improved the percentage of within 1-level matches from 67% to 88% (P=.0001). The addition of hand-carried ultrasound failed to improve the assessments of aortic stenosis, aortic regurgitation, and mitral regurgitation. CONCLUSION: Adding hand-carried ultrasound to physical examination increases the accuracy of hospitalists' assessment of left ventricular dysfunction, cardiomegaly, and pericardial effusion, and fails to improve assessment of valvular heart disease. The clinical benefit achieved by improved immediacy of this information has not been determined. An important limitation is that the study assessed only 1 level of training in hand-carried ultrasound.

Hospitalist performance of cardiac hand-carried ultrasound after focused training.

PURPOSE: Because the training that noncardiologists require to perform cardiac hand-carried ultrasound has not been defined, we studied how well hospitalists perform hand-carried echocardiography after limited training. METHODS: Ten hospitalists completed a focused training program that included performing an average of 35 hand-carried echocardiograms. Hospitalists' echocardiograms were compared with gold-standard conventional echocardiograms, and hospitalists were compared with 5 certified echocardiography technicians in their ability to acquire, measure, and interpret hand-carried ultrasound images and with 6 senior cardiology fellows in their ability to interpret echocardiograms. RESULTS: Echocardiography technicians had significantly higher performance scores for image acquisition, measurement, and interpretation than hospitalists. Senior cardiology fellows outperformed hospitalists in most aspects of image interpretation. For hospitalists, learning image acquisition was more difficult than image interpretation. CONCLUSIONS: Hospitalists can learn aspects of hand-carried echocardiography, but after 35 training echocardiograms cannot replicate the quality of conventional echocardiography. Whether the lower performance skills are important will depend on the clinical context of hand-carried echocardiography performed by hospitalists.

The rate at which residents learn to use hand-held echocardiography at the bedside.

PURPOSE: Because there is little information about the training that general internists require to perform hand-carried cardiac ultrasonography (HCU), we studied the rate of learning of a group of medical residents performing HCU after minimal formal training. METHODS: Medical residents on the inpatient services at Johns Hopkins Bayview Medical Center received formal training in HCU consisting of 15-30 minutes of didactic instruction about the principles of echocardiography, followed by ongoing one-on-one instruction in performing HCU and subsequent ongoing one-on-one training from a certified echocardiography technician as they were doing scans. The residents were shown how to position the patient to obtain 2-dimensional echo images from the parasternal short and long axes and apical 4-chamber views, and how to obtain color-flow Doppler images across the mitral and aortic valves. Residents were asked to determine whether pericardial effusion was present and to assess left ventricular size, left ventricular function, and the mitral and aortic valves. The residents performed cardiac physical examination and HCU independently on patients who had a conventional transthoracic echocardiogram (CTTE) performed within 24 hours of the HCU. The residents' HCU results were compared with the CTTE results by a cardiologist specializing in echocardiography. The rates at which residents gained technical proficiency and skills in interpreting their studies were measured by linear regression to fit various outcome variables against their experience at scanning as gauged by the number of scans performed. RESULTS: Thirty medical residents performed a total of 231 HCU studies. Linear regression models showed that the residents' overall technical proficiency skills improved at the rate of 0.79 (95% confidence interval [CI] 0.53-1.04) points on an overall assessment index (0-3 scale) per 10 scans completed. Interpretation accuracy improved at a rate of 1.01 (95% CI 0.69-1.39) points per 10 scans as measured by an interpretation accuracy index (0-3 scale). Because scanning efforts and instruction in HCU occurred during residents' usual rotation duties, some residents gathered experience in HCU slowly and sporadically. CONCLUSION: This study, the first prospective, experimental effort of its kind, shows that residents as a group learned important aspects of HCU scanning and interpretation at a reasonably rapid rate.