Intrascanner and interscanner variability of magnetization transfer‐sensitized balanced steady‐state free precession imaging

Recently, a new and fast three‐dimensional imaging technique for magnetization transfer ratio (MTR) imaging has been proposed based on a balanced steady‐state free precession protocol with modified radiofrequency pulses. In this study, optimal balanced steady‐state free precession MTR protocol parameters were derived for maximum stability and reproducibility. Variability between scans was assessed within white and gray matter for nine healthy volunteers using two different 1.5 T clinical systems at six different sites. Intrascanner and interscanner MTR measurements were well reproducible (coefficient of variation: c_v < 0.012 and c_v < 0.015, respectively) and results indicate a high stability across sites (c_v < 0.017) for optimal flip angle settings. This study demonstrates that balanced steady‐state free precession MTR not only benefits from short acquisition time and high signal‐to‐noise ratio but also offers excellent reproducibility and low variability, and it is thus proposed for clinical MTR scans at individual sites as well as for multicenter studies. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.     

The hematopoietic stem cells of alpha-thalassemic mice

The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.     

Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.      

Intraportal chemotherapy in colorectal carcinoma as an adjuvant modality

Liver metastases of colorectal origin arise from malignant cells entering the portal venous circulation. Four hundred sixty patients from 7 participating institutions have been entered in a prospective randomized trial to assess the value of adjuvant portal venous infusion to prevent liver metastases following curative colorectal cancer surgery. By preoperative randomization, patients were assigned to surgery alone (control arm) or to portal liver infusion with 5-fluorouracil (5-FU) (500 mg/m² daily × 7, continuous infusion during the first 7 postoperative days) and mitomycin C (10 mg/m², 24 hours postoperatively as a 2-hour infusion). A portal venous catheter was placed through any side branch of the mesenteric venous system during laparotomy for the primary tumor. Using the transabdominal route, there have been no catheter-related complications. Despite a large cumulative dose of 5-FU given during the immediate postoperative period, the systemic side effects were minimal. Overall hospital mortality in this study was 1.85% and was not influenced by the adjuvant treatment. This rate is considerably lower than that reported by previous multicenter trials and by the surgical literature, and it indicates an advance in surgical technique and pre-/postoperative patient management in this type of elective surgery.Three hundred seventy-eight patients (187 controls, 191 infusion patients) are completely evaluable for recurrence and survival. After a median follow-up of 24 months, 43 recurrences have been observed in the control group and 34 in the infusion group (p<0.05). Liver metastases were present in 18 control patients and in 14 infusion patients. Twenty-five patients in the control group and 18 patients in the infusion group died of recurrent disease. Due to the low number of recurrences in this study, it is too early to draw survival conclusions. Several controlled trials using adjuvant portal infusion are in progress. They also showed the feasibility of this approach and they suggested that adjuvant cytotoxic liver infusion may reduce the incidence of liver metastases without significantly increasing morbidity and mortality. It is too early, however, to recommend adjuvant portal infusion outside a clinical trial setting and such treatment should still be restricted to well-designed prospective protocols.

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Resumen Las metástasis hepáticas de origen colorrectal se originan en células malignas que ingresan a la circulación venosa portal. Cuatro cientos sesenta pacientes de 7 instituciones participantes han sido introducidos a un ensayo clínico prospectivo y aleatorizado para determinar el valor de la terapia adyuvante con perfusión venosa portal en la prevención de las metástasis hepáticas después de cirugía colorrectal curativa. Mediante aleatorización preoperatoria, los pacientes fueron asignados a un grupo manejado con cirugía solamente (grupo control) o al grupo de infusión portal del hígado con 5-fluoruracilo (500 mg/m² diarios × 7 en infusión continua por los 7 primeros días postoperatorios) y mitomicina-C (10 mg/m² por 24 horas postoperatorias como infusión de 2 horas). El catéter venoso portal fue colocado a través de cualquier rama del sistema venoso mesentérico en el curso de la laparotomía para el tumor primario. Con el uso del abordaje transabdominal no se han presentado complicaciones relacionadas con el catéter. A pesar de la elevada dosis acumulativa de 5-FU administrada en el periodo postoperatorio inmediato, los efectos sistémicos han sido mínimos. La tasa global de mortalidad hospitalaria en este estudio es de 1.85% y no aparece afectada por la terapia adjuvante. Esta tasa es considerablemente menor que la informada en ensayos multicéntricos y en la literatura quirúrgica y es indicativa de un avance en la técnica operatoria y en el manejo pre-/postoperatorio de los pacientes en este tipo de cirugía electiva.Tres cientos setenta y ocho pacientes (187 del grupo control, 191 del grupo de infusión) son susceptibles de valoración total en cuanto a recurrencia y supervivencia. Después de un seguimiento promedio de 24 meses, se han presentado 43 recurrencias en el grupo control y 34 en el grupo de infusión (p <0.05). Se presentaron metástasis hepáticas en 18 pacientes del grupo control y en 14 del grupo de infusión. Veinte y cinco pacientes en el grupo control y 18 en el grupo de infusión murieron como consecuencia de enfermedad recurrente. Debido al bajo número de recurrencias observado en el estudio, es todavía demasiado temprano para derivar conclusiones en cuanto a supervivencia.Varios ensayos clínicos controlados utilizando infusión portal adyuvante están siendo realizados; también han demostrado la factibilidad de este enfoque y sugieren que la infusión hepática con agentes citotóxicos puede reducir la incidencia de metástasis hepáticas sin que haya un aumento significativo en la morbilidad o mortalidad. Sin embargo, es todavía muy pronto para poder recomendar la terapia adyuvante con infusión portal por fuera del marco de los ensayos clínicos y tal forma de tratamiento debe permanecer restringida a protocolos prospectivos debidamente diseñados.

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Résumé Les métastases hépatiques des cancers colo-rectaux trouvent leur origine dans les cellules malignes qui pénètrent dans la circulation portale. Quatre cent soixante malades provenant de 7 institutions ont constitué la base d'un essai prospectif randomisé destiné à évaluer la valeur d'une perfusion portale à l'aide d'un agent chimique dont le but est de prévenir les métastases après chirurgie curative du cancer colo-rectal. En préopératoire, les malades ont été choisis au hasard pour constituer 2 groupes: (a) malades traités par la chirurgie (groupe de contrôle), (b) opérés recevant une perfusion portale de 5-FU (500 mg/m²/jour × 7) infusée continuement les 7 premiers jours post-opératoires et de mitomycine C (10 mg/m²/24 heures après l'intervention) pendant 2 heures. Le cathéter veineux portal fut placé dans une collatérale quelconque du système veineux mésentérique au cours de l'opération. Il n'y eut aucune complication dûe au cathéter intra-abdominal. Malgré une dose importante de 5-FU administrée dans la période post-opératoire immédiate, les effets secondaires systémiques furent minimes. La mortalité globale au cours de l'hospitalisation fut de 1.85% et sans relation avec la chimiothérapie. Ce taux est remarquablement inférieur à ceux rapportés par de multiples centres ou dans la littérature. Il est l'expression d'un progrès dans la technique chirurgicale et les soins pré- et postopératoires.378 malades (groupe de contrôle: 187, perfusés: 191) ont permis une évaluation exacte de la récidive et de la survie. Après un suivi moyen de 24 mois, il a été observé 43 récidives dans le groupe de contrôle et 34 dans le groupe traité (p<0.05). Des métastases hépatiques furent découvertes 18 fois dans le premier groupe et 14 fois dans le second. Les malades moururent de récidive 25 fois dans le groupe de contrôle et 18 fois dans le groupe traité par perfusion. En raison du faible nombre des récidives dans cette étude il est trop tôt pour tirer des conclusions sur la durée de la survie.Plusieurs essais contrôlés de traitement par perfusion portale sont en cours. Ils montrent également que la méthode peut être pratiquée et ils suggèrent que la perfusion hépatique par un agent cytotoxique peut réduire le nombre des métastases sans augmenter significativement la morbidité et la mortalité. Il est trop tôt cependant pour recommander la pratique courante de cette méthode. Elle reste sous essai clinique contrôlé et doit s'appliquer seulement à partir de protocoles prospectifs bien définis.

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See Acknowledgment for principal investigators.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。