Coronary Magnetic Resonance Angiography

Coronary magnetic resonance angiography (CMRA) is a technique in clinical evolution. Current clinical applications include assessment for coronary anomalies, aneurysms, bypass graft patency, and, in experienced centers, the exclusion of proximal and multivessel coronary artery disease (CAD). As local expertise increases and more extensive multicenter data become available, additional applications will be established. CMRA promises to supplement and in some cases obviate the need for X-ray contrast angiography, and to expand our understanding of the pathophysiology of CAD. Zusammenfassung Die Magnetresonanzangiographie der Koronargefäße (CMRA) ist eine sich ständig weiterentwickelnde Technik. Etablierte Anwendungen sind zurzeit die Beurteilung von koronaren Anomalien, Aneurysmen und der Durchgängigkeit von Bypasses. Auch der Ausschluss proximaler Koronarstenosen und einer koronaren Mehrgefäßerkrankung ist in einigen spezialisierten Zentren möglich. Mit zunehmender Erfahrung der jeweiligen Anwender und der Verfügbarkeit von Ergebnissen großer multizentrischer Studien können zukünftig weitere klinische Anwendungen etabliert werden. In der Zukunft könnte die CMRA ergänzende Informationen zur Indikationsstellung einer konventionellen Röntgenangiographie bringen und in einigen Fällen diese Untersuchung sogar ersetzen. Die CMRA wird unseren Einblick in die Pathophysiologie der koronaren Herzerkrankung sicher erweitern.     

Diagnosis of ligament rupture of the ankle joint: Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on. 122 of these patients had ligament ruptures.

At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures.

Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.     

Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophenolate mofetil and cyclosporine.

There are few pharmacokinetic data for mycophenolate mofetil (MMF) when used in combination with cyclosporine (CsA) in pediatric liver transplant recipients. The aim of this study was to assess the pharmacokinetics of MMF in stable pediatric liver transplant patients and estimate the dose of MMF required to provide a mycophenolic acid (MPA) exposure similar to that observed in adult liver transplant recipients receiving the recommended dose of MMF (target area under the plasma concentration-time curve from 0 to 12 hours [AUC(0-12)] for MPA of 29 mug.hour/mL in the immediate posttransplantation period and 58 microg x hour/mL after 6 months). A 12-hour pharmacokinetic profile was collected for 8 pediatric patients (mean age 20.9 months) on stable doses of MMF and CsA who had received a liver transplant > or = 6 months prior to entry and who had started on MMF within 2 weeks of transplantation. Mean MMF dosage was 285 mg/m(2) (range, 200-424 mg/m(2)). Of 8 patients, 7 had a MPA AUC(0-12) (range, 11.0-37.2 microg x hour/mL) well below the target. One patient had an AUC(0-12) > or = 58 microg x hour/mL but was considered an outlier and was excluded from analyses. Mean MPA AUC(0-12) and maximum plasma concentration values were 22.7 +/- 10.5 microg x hour/mL and 7.23 +/- 3.27 microg/mL, respectively; values normalized to 600 mg/m(2) (the approved pediatric dose in renal transplantation) were 47.0 +/- 21.8 microg x hour/mL and 14.5 +/- 4.21 microg/mL. In conclusion, assuming that MPA exhibits linear pharmacokinetics, when used in combination with CsA, a MMF dose of 740 mg/m(2) twice daily would be recommended in pediatric liver transplant recipients to achieve MPA exposures similar to those observed in adult liver transplant recipients. This finding should be confirmed by a prospective trial.     

Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

Chronic cyclosporine nephrotoxicity in renal transplantation

Although extensively studied, the pathophysiologic characteristics of chronic cyclosporine (CsA) nephrotoxicity are still far from being completely understood. The recognition of chronic CsA nephrotoxicity in allografted kidneys is hampered by a lack of easily assessable sensitive and specific markers. Long-term results of CsA withdrawal trials and trials that evaluated CsA sparing or withdrawal after the diagnosis of chronic allograft nephropathy (CAN) have shown that chronic CsA nephrotoxicity has a more important role in the etiology of late transplant dysfunction than appreciated before. Various hypotheses have explained the renal structural changes of chronic CsA nephrotoxicity including ischemia, cellular toxicity, and the stimulation of renal fibrosis by growth factors or cytokines. Possible ways to prevent chronic CsA nephrotoxicity include improved therapeutic drug monitoring and CsA withdrawal or avoidance. Patients with aspecific CAN in late biopsy may benefit from withdrawal of CsA or a reduction of its dose. Current knowledge is being discussed. It is concluded that in the near future more strategies are likely to be used to prevent loss of allograft function as a result of drug toxicity.     

Is there a place for gastroenterostomy in patients with advanced cancer of the head of the pancreas?

There remains doubt about the need for gastroenterostomy in patients with advanced cancer of the pancreatic head, performed either prophylactically or when passage of food becomes impossible. The records of 142 patients admitted for advanced pancreatic cancer to the Erasmus University Hospital over a period of 11 years were reviewed. We concentrated especially on the pre- and postoperative intake of food in cases involving gastroenterostomy and the morbidity and mortality associated with abdominal surgery in these patients. Of 129 patients without symptoms of gastric outlet obstruction at the time of diagnosis, 31 underwent prophylactic gastroenterostomy. The procedure did not prevent gastric outlet obstruction in 4 patients. Of the remaining 98 patients, 15 developed gastric outlet obstruction. Cox proportional hazards analysis showed no significant difference in the interval to the occurrence of a symptomatic obstruction between these two groups, taking into account other covariables. Postoperative complications and mortality regarding a gastroenterostomy were high, ranging from 9% to 41% and 11% to 33%, respectively. Our results do not indicate that prophylactic gastroenterostomy may significantly prevent future gastric outlet obstruction; therefore, as it also increases morbidity, it should not be performed. A gastroenterostomy to relieve symptoms should be considered carefully, as the success rate is low and is accompanied by a considerable incidence of morbidity and mortality.

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Resumen Persiste la duda sobre la necesidad de practicar gastroenterostomía en pacientes con cáncer avanzado de la cabeza del páncreas, así sea profiláctica o en presencia de obstrucción al paso de los alimentos. Se revisaron las historias de 142 pacientes con cáncer avanzado de la cabeza del páncreas en el Hospital de la Universidad de Erasmo observados en un periodo de 11 años. El estudio se concentré especialmente sobre la ingesta pre y postoperatoria de alimentos en los pacientos con gastroenterostomía y en la morbilidad y mortalidad asociada con la cirugía abdominal. De 129 pacientes libres de síntomas de obstrucción en el momento del diagnóstico, 31 fueron sometidos a gastroenterostomía profiláctica; el procedimiento no logró prevenir la obstrucción gástrica en 4 casos. De los 98 pacientes restantes, 15 desarrollaron obstrucción gástrico. El análisis proporcional de Cox no demostró diferencia significativa en el intervalo transcurrido hasta la aparición de los sintomas entre los dos grupos, tomando en consideración diversas variables. Las tasas de complicaciones y de mortalidad postoperatoria en relación con la gastroenterostomía fueron elevadas, 9–41% y 11–33%, respectivamente. Nuestros resultados no indican que la gastroenterostomía profiláctica pueda prevenir la obstrucción gástrica y, por cuanto incrementa la morbilidad, no debe ser realizada. La gastroenterostomía por razones de sintomatologia debe ser cuidadosamente considerada, puesto que la tasa de éxito es baja y se acompana de considerable morbilidad y mortalidad.

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Résumé Réaliser une gastroentérostomie de faÇon prophylactique ou seulement lorsque l'alimentation devient impossible chez un patient ayant un cancer de la tÊte du pancréas reste une question sans réponse. Les dossiers de 142 patients ayant un cancer avancé de la tÊte du pancréas, observés à l'HÔpital Universitaire Erasmus en l'espace de 11 ans, ont été revus. Nous avons noté la possibilité d'alimentation en périodes préet postopératoire ainsi que la morbidité et mortalité en rapport avec la chirurgie chez ces patients. Des 129 patients n'ayant pas de symptÔmes d'obstruction postpylorique au moment du diagnostic, 31 ont eu une gastroentérostomie à titre prophylactique. Cette intervention n'a pu prévenir l'obstruction chez 4 de ces patients. Des 98 autres patients, 15 ont développé une obstruction postpylorique. Une analyse multifactorielle selon le modèle de Cox n'a pu démontrer de différence significative entre les deux groupes pour l'intervalle entre le moment du diagnostic et la survenue de l'obstruction. Le taux de complications et de décès postopératoires après gastroentérostomie était élevée, variant respectivement entre 9% et 41% et 11% et 33%. Nos résultats indiquent que la gastroentérostomie à titre prophylactique ne prévient pas la survenue d'une obstruction postpylorique mais qu'elle accroÎt la morbidité. Dans ces conditions, la gastroentérostomie ne devrait Être réalisée qu'en cas d'obstruction symptomatique, mais en sachant qu'elle n'est pas toujours couronnée de succès et que les taux de mortalité et de morbidité ne sont pas nuls.

     

How does prosthesis head size affect vibration transmission in ossiculoplasty?

OBJECTIVES: The transmission of vibrations from the tympanic membrane to the stapes footplate by an ossicular reconstruction prosthesis is affected by the size of the prosthesis head. We sought to determine if augmenting or reducing the head size of prosthesis had a systematic effect on transmission of vibrations to the stapes. STUDY DESIGN: We conducted a fresh cadaveric temporal bone middle ear study. METHODS: The incus was replaced with a prosthesis using a tympanic membrane to stapes head (TASH)-type hydroxyapatite prosthesis in nine fresh cadaveric temporal bones. Three prosthesis head sizes were created: unaltered, reduced, and augmented. Stapes vibrations were measured with a laser Doppler vibrometer in response to acoustic frequency chirps at 90 dB SPL. RESULTS: All three head size prostheses resulted in smaller stapes vibrations than the intact ear. There was no difference in the vibration transmission between the three different head sizes. All prostheses showed a vibration loss of 10 to 15 dB compared to the intact ear. CONCLUSIONS AND SIGNIFICANCE: Within the range of sizes tested, prosthesis head size had little impact on vibration transmission to the stapes footplate.     

Pain after use of the central third of the patellar tendon for cruciate ligament reconstruction: 33 patients followed 2-3 years

We performed reconstruction of the anterior cruciate ligament in 33 patients using the central third of the patellar tendon. In 20 patients we did an arthroscopies! ly-assisted procedure, while 13 patients had an additional mini-arthrotomy through the gap in the patellar tendon. After 2-3 years the subjective knee function, according to the Lysholm score, was excellent or good in 18 knees and fair or poor in 15 knees, mainly due to anterior knee pain. Although 18 patients complained about anterior knee pain, only 1 patient required further surgery. After the operatio the patella had a lower position. A flexion contractur was found in 7 patients, and 13 had heterotopic bon formation at the apex of the patella. Although stabilit was restored in 31 of the 33 reconstructed knees anterior knee pain was a frequent complicatior There were no correlations between the anterior kne pain and patellar height, flexion contracture or hetei otopic bone formation.     

IL-12 and IL-23: master regulators of innate and adaptive immunity

Summary: Initiation of an effective immune response requires close interactions between innate and adaptive immunity. Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell‐derived factors regulate the immune system to protect the host from infections and prevent tumor development. In this review, we focus on the function of interleukin (IL)‐23, a new member of the IL‐12 family of regulatory cytokines produced by activated macrophages and dendritic cells. We propose that IL‐12 and IL‐23 promote two distinct immunological pathways that have separate but complementary functions. IL‐12 is required for antimicrobial responses to intracellular pathogens, whereas IL‐23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression.     

Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A.

BACKGROUND: Major depressive disorder (MDD) shows increased coronary artery disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men; CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients. METHODS: We measured fasting am serum CRP (high sensitivity, CRP(hs)) and SAA in 18 unmedicated, remitted women with MDD (mean age 41 +/- (SD)12, body mass index (BMI) 25.2 +/- 4.1 kg/m(2)) and 18 BMI-matched healthy control subjects (age 36 +/- 10, BMI 25.3 +/- 3.8 kg/m(2)) on 2 separate occasions, > or = 6 days apart. RESULTS: Repeat SAA and CRP(hs) measurements strongly correlated across study days (SAA: r = .83, p < .001; CRP(hs): r = .94, p < .001). Both SAA (5.30 +/- 3.39 vs. 2.84 +/- 1.87 mg/L, p < .005) and CRP(hs) (3.23 +/- 3.17 vs. 1.12 +/- 1.45 mg/L; p < .01) were significantly elevated in MDD women versus controls. CONCLUSIONS: Elevated SAA and CRP(hs) in remitted, unmedicated women with MDD indicate a pro-inflammatory state unrelated to current depressive symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms may in part underlie findings of increased CAD risk in MDD.