Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

Vascularized composite allotransplantation (VCA) has emerged as a viable limb replacement strategy for selected patients with upper limb amputation. However, allograft rejection has been seen in essentially all reported VCA recipients indicating a requirement for substantial immunosuppressive therapy. Calcineurin inhibitors have served as the centerpiece agent in all reported cases, and CNI-associated complications associated with the broad therapeutic effects and side effects of calcineurin inhibitors have been similarly common. Recently, belatacept has been approved as a calcineurin inhibitor replacement in kidney transplantation, but to date, its use in VCA has not been reported. Herein, we report on the case of a hand transplant recipient who developed recurrent acute rejection with alloantibody formation and concomitant calcineurin inhibitor nephrotoxicity, all of which resolved upon conversion from a maintenance regimen of tacrolimus, mycophenolate mofetil and steroids to belatacept and sirolimus. This case indicates that belatacept may be a reasonable maintenance immunosuppressive alternative for use in VCA, providing sufficient prophylaxis from rejection with a reduced side effect profile, the latter being particularly relevant for nonlife threatening conditions typically treated by VCA.

Smoking behavior, attitudes, and cessation counseling among healthcare professionals in Armenia.

BACKGROUND: Smoking cessation counseling by health professionals has been effective in increasing cessation rates. However, little is known about smoking cessation training and practices in transition countries with high smoking prevalence such as Armenia. This study identified smoking-related attitudes and behavior of physicians and nurses in a 500-bed hospital in Yerevan, Armenia, the largest cancer hospital in the country, and explored barriers to their effective participation in smoking cessation interventions. METHODS: This study used mixed quantitative and qualitative methods. Trained interviewers conducted a survey with physicians and nurses using a 42-item self-administered questionnaire that assessed their smoking-related attitudes and behavior and smoking cessation counseling training. Four focus group discussions with hospital physicians and nurses explored barriers to effective smoking cessation interventions. The focus group sessions were audio-taped, transcribed, and analyzed. RESULTS: The survey response rate was 58.5% (93/159) for physicians and 72.2% (122/169) for nurses. Smoking prevalence was almost five times higher in physicians compared to nurses (31.2% vs. 6.6%, p < 0.001). Non-smokers and ex-smokers had more positive attitudes toward the hospital's smoke-free policy compared to smokers (90.1% and 88.2% vs. 73.0%). About 42.6% of nurses and 26.9% of physicians reported having had formal training on smoking cessation methods. While both groups showed high support for routinely assisting patients to quit smoking, nurses more often than physicians considered health professionals as role models for patients. CONCLUSIONS: This study was the first to explore differences in smoking-related attitudes and behavior among hospital physicians and nurses in Yerevan, Armenia. The study found substantial behavioral and attitudinal differences in these two groups. The study revealed a critical need for integrating cessation counseling training into Armenia's medical education. As nurses had more positive attitudes toward cessation counseling compared to physicians, and more often reported having cessation training, they are an untapped resource that could be more actively engaged in smoking cessation interventions in healthcare settings.

Isolated left ventricular apical hypoplasia: a new congenital anomaly described with cardiac tomography.

OBJECTIVE: To describe cardiac tomography findings of an apparently new, presumably congenital, left ventricular (LV) abnormality noted consistently in three patients. PATIENTS: Three patients presenting with non-specific symptoms including fatigue, shortness of breath, or chest discomfort were evaluated with cardiac tomography for cardiac structure and function. RESULTS: Findings from the three patients were very similar: a truncated and spherical LV with abnormal diastolic and systolic function, invagination of fatty material into the myocardium of the defective LV apex, origin of a complex papillary network in the anteroapical LV, and an elongated right ventricle wrapping around the deficient apex. CONCLUSIONS: Isolated LV apical hypoplasia is a unique, presumably congenital, cardiac anomaly that is an important condition to recognise.

Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis.

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system characterized by progressive neurological dysfunction. No curative therapy is currently available, and approximately 80-90% of afflicted individuals are ultimately disabled. Interferon beta (IFNbeta) has been shown to decrease clinical relapses, reduce brain disease activity, and possibly slow progression of disability. However, the overall effect of treatment is partial and a substantial number of patients are considered poor or nonresponders. For this report, we tested the pharmacogenomic effects of eight polymorphisms in the interferon receptor genes (IFNAR1 and IFNAR2) in a group of 147 patients undergoing open-label IFNbeta therapy. Overall, no significant differences in the distribution of responders and nonresponders, classified based on prospectively acquired primary and secondary clinical end points, were observed when stratified by any of the studied IFNAR gene polymorphisms. A trend detected with a single nucleotide polymorphism SNP 16469 (A/T) located at the third intron of the IFNAR1 gene, suggesting modest association with relapse-free status, will require confirmation in an independent data set. In addition, no significant association was observed of any of the IFNAR gene polymorphisms with susceptibility to MS, as studied by a family-based association analysis.

Carotid MR angiography: phase II study of safety and efficacy for MS-325.

PURPOSE: To evaluate the safety and efficacy of MS-325 in patients suspected of having carotid arterial disease. MATERIALS AND METHODS: Fifty carotid arteries in 26 patients were imaged with three-dimensional spoiled gradient-recalled-echo magnetic resonance (MR) angiography at 5 and 50 minutes after injection of MS-325. MS-325 was administered intravenously as a single dose of 0.01, 0.03, or 0.05 mmol per kilogram of body weight as determined with a dose randomization scheme for four, nine, and 13 patients, respectively. Safety, including clinical laboratory changes and electrocardiographic monitoring, was assessed until approximately 3 days after injection. Conventional contrast agent-enhanced angiography was used as the standard of reference. Independent readers blinded to the dose interpreted the MR angiographic and conventional images. Images were assessed for location and extent of carotid arterial stenosis. RESULTS: There were no severe or serious adverse events. For the determination of clinically significant stenosis (>70%) on the 5-minute images, sensitivity, specificity, and accuracy (P =.07, three-way comparison) were 100%, 100%, and 100%; 63%, 100%, and 88%; and 40%, 75%, and 55% at 0.01, 0.03, and 0.05 mmol/kg, respectively. Sensitivity and specificity for images at 50 minutes after MS-325 administration showed the same trends as the 5-minute images. CONCLUSION: Overall accuracy for MS-325-enhanced carotid MR angiography performed during steady-state conditions of circulating contrast agent approximately 5 minutes after injection was high (88%-100%) at 0.03 and 0.01 mmol/kg. MS-325 was well tolerated at all evaluated doses.

The clinical value of ferric ammonium citrate: a positive oral contrast agent for T1-weighted MR imaging of the upper abdomen.

This study was undertaken to determine whether ferric ammonium citrate (FAC), a positive magnetic resonance (MR) contrast agent, is of clinical value in demonstrating or excluding pathology of the upper gastrointestinal tract. A retrospective review was performed of pre- and post-FAC studies of MR examinations in 203 patients from phase II and III clinical trials in whom final diagnoses had been established based on the results of biopsy, surgery, or independent imaging procedures. Two independent reviewers made randomized and blinded assessments of the stomach, duodenum, and pancreas. FAC significantly increased the certainty of diagnosis for normal studies of the stomach and duodenum for both readers (P < 0.001) and for abnormal studies of the stomach for one reader (P = 0.004). FAC also significantly increased the certainty of diagnosis for normal pancreas for one reader (P < 0.001). FAC significantly (P < 0.001) increased accuracy and specificity for diagnoses involving the stomach and duodenum for both readers and for one reader for the pancreas. There was significant improvement in sensitivity for gastric diagnoses (P = 0.013) for one reader but not for the duodenum or pancreas. We conclude that FAC is helpful in demonstrating and excluding upper gastrointestinal pathology on MR.

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging.

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.

Trained nurses can provide safe and effective sedation for MRI in pediatric patients.

PURPOSE: To determine the success rate, safety and complications using a standard protocol and trained nurses to provide sedation for MRI under the supervision of a radiologist. MATERIALS AND METHODS: Nurses were trained to provide sedation via a standard protocol for pediatric patients undergoing diagnostic MRI. Oral chloral hydrate (80-100 mg x kg(-1)) was used for children less than 18 mo of age. Older children received either 1-6 mg x kg(-1) pentobarbital i.v., with or without 1-2 microg x kg x hr(-1) fentanyl, or 25 mg x kg(-1) thiopental pr. Sedation was defined as successful if it allowed completion of the MRI without image distorting patient movement. The records of 572 MRIs performed on 488 pediatric patients (mean age 5+/-4 yr; age 2 mo-14 yr) from 1991 to July 1995 were reviewed to determine the success rate and complications using the sedation program. RESULTS: Most, 91.8% (525/572), of the MRIs were successfully completed in 445 patients. The reasons for failure were inadequate sedation (45, 95.7%) and coughing (2, 4.2%). The failure rate was much higher before 1994 (38/272, 14%) than after (9/300, 3%; P<0.0001). Failure was more common if rectal thiopental was used (23/172, 14%) than intravenous pentobarbital (19/256, 7.4%; P<0.05). The failure rate was also high in patients with a history of a behavioural disorder (10/59, 17%). There were no deaths or unexpected admissions as a result of the sedation program. CONCLUSION: A high success rate can be achieved as experience is gained using a standard protocol and trained nurses to sedate children for MRI.

Right transatrial approach to relieve pulmonary stenosis in patients with corrected transposition of the great vessels: a new operation without use of an extracardiac conduit.

BACKGROUND: A new operation to relieve pulmonary obstruction is proposed for patients with corrected transposition of the great vessels and pulmonary stenosis (PS). A right transatrial approach involves excising or detaching the right-sided atrioventricular valve (AV). Next, the pulmonary outflow tract is opened wide with an incision extending from the right-sided ventricle upward across the AV valve annulus. This incision extends into the main trunk of the pulmonary artery located behind the right atrium. A patch, with or without implantation of a pulmonary valve prosthesis, widens the outflow tract, thus avoiding use of an extracardiac conduit. METHOD: We describe this operation performed in a 51-year-old man who had previously undergone correction with an extracardiac conduit that had become obstructed. The patient had severe right-sided AV valve insufficiency and complete heart block with a functioning transvenous pacemaker. We replaced the right-sided AV valve and positioned the permanent pacemaker lead outside of the prosthetic skirt. The PS was corrected as described above and a pulmonary prosthetic valve implanted. Use of an extracardiac conduit was avoided altogether. CONCLUSION: This technique may be applicable even without excising the right-sided AV valve. The clinical result for our patient is still optimal 4 years after surgery.

Magnetic resonance first-pass myocardial perfusion imaging: clinical validation and future applications.

Clinical studies suggest that magnetic resonance first-pass (MRFP) perfusion imaging is comparable to current diagnostic tests that are used clinically for the assessment of myocardial perfusion. In addition, magnetic resonance imaging (MRI) perfusion imaging is a noninvasive method for determining myocardial blood flow. The spatial resolution (in-plane spatial resolution < 3 mm) is sufficient to differentiate between subendocardial perfusion and subepicardial perfusion. The measurement can be repeated regularly without any adverse effects for the patient. MRI perfusion measurements can be combined with the evaluation of global function and regional wall thickening. Currently, there is no other imaging technique that offers similar advantages. The MRI perfusion measurements can be carried out during baseline conditions and during maximal hyperemia induced with either adenosine or dipyridamole. The ratio of the measured myocardial blood flows provides an estimate of the absolute and relative myocardial perfusion reserve. The perfusion reserve determined with MRFP imaging is a quantitative measure for the assessment of the collateral-dependent myocardial flow. Based on the available data using MRFP perfusion imaging, the current clinical first-line perfusion imaging tests are going to be challenged in the near future. J. Magn. Reson. Imaging 1999;10:676-685.

Contrast enhanced body magnetic resonance angiography.

The use of gadolinium contrast for body MRA is reviewed. Considerations for timing of the bolus of contrast are discussed. The utility of this technique is illustrated through clinical examples. Contrast enhanced MRA is rapidly replacing conventional angiography for many applications.

Myocardial viability.

This article reviews various means to assess myocardial viability by imaging, and provides recommendations for current clinical practice. This article also discusses future directions in assessing myocardial viability.

Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data.

The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide contrast agent, are presented. One hundred and four patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg. Overall, 15% patients reported a total of 33 adverse events, regardless of causality. The adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and rash (2.9%). No serious adverse events were reported during the 48 hour observation period. There were no clinically significant effects on vital signs, physical examination, and laboratory results. Ferumoxtran-10 is a safe and well tolerated MR contrast agent.

Direct comparison of an intravascular and an extracellular contrast agent for quantification of myocardial perfusion. Cardiac MRI Group.

A direct comparison of extracellular and intravascular contrast agents for the assessment of myocardial perfusion was carried out in a porcine model (N = 5) with a flow-limiting occluder on the left anterior descending coronary artery. Rapid imaging during the first pass of an extracellular or intravascular contrast agent with a saturation-recovery-prepared TurboFLASH sequence showed comparable peak contrast-to-noise enhancements in myocardial tissue regions with flows averaging 1.1 +/- 0.2 at baseline to 4.8 +/- 0.6 ml/min/g during hyperemia. The coefficient of variation between the MR estimates of blood flow with Gadomer-17 and the microsphere blood flow measurements was 11 +/- 11%, while the corresponding co-efficient of variation for blood flow estimates with the extracellular CA was 23 +/- 11%. Blood volume differences between rest and hyperemia observed with the intravascular tracer were significant (Vvasc(rest) = 0.078 +/- 0.013 ml/g, versus Vvasc(hyperemia) = 0.102 +/- 0.019 ml/g; p < 0.05). The effects of water exchange were minimized through the choice of pulse sequence parameters to provide blood volume estimates consistent with the changes expected between rest and hyperemia. This study represents the first application of multiple indicators in first pass imaging studies for the assessment of myocardial perfusion. The use of an intravascular instead of an extracellular contrast agent allows a reduction of the degrees of freedom for modeling tissue residue curves and results in improved accuracy of blood flow estimates.