Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial.

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.     

Takayasu arteritis in children

Takayasu arteritis (TA) is a large vessel vasculitis that usually affects young female patients during the second and third decades of life, but has been reported in children as young as 24 months of age. Aim of this report was to describe four children (two girls) with TA, as well as summarizing main published studies. The mean age at presentation of our cases was 11 years (range 8–15). Three patients were Caucasians and one Asian. Arterial hypertension was the commonest mode of presentation followed by systemic symptoms. Other related symptoms were due to ischemia and consisted of abdomen, chest, and limb pain. An abdominal bruit was noted in only one patient. Inflammation markers were always abnormal. Angiography was performed in all cases; left subclavian artery and common carotid artery were more frequently involved. Renal artery stenosis was observed in two patients. One boy was diagnosed as having an associated immune deficiency (Wiskott-Aldrich syndrome). Treatment modalities included prednisone (n = 4), methotrexate (n = 3), and mycophenolate mofetil (MMF) (n = 1). Surgery was required in two patients. Follow-up ranged from 3 to 10 years since diagnosis. In three cases antihypertensive drugs and methotrexate were stopped, and prednisone was reduced to 7.5 mg/day.     

Development of an enzyme-linked immunosorbent assay (ELISA) for detecting IgA antibodies to the Epstein-Barr virus

A 3-step enzyme-linked immunosorbent assay (ELISA) was developed for detecting IgA antibodies to purified Epstein-Barr virus (EBV) polypeptides. The 3-step procedure included the use of a mouse anti-human IgA monoclonal antibody (MAb) to amplify the IgA reaction. The 2 major EBV proteins used in this assay were the 125-kDa component (gp125) associated with the viral capsid antigen (VCA) complex and a major glycoprotein (gp250/200) associated with the membrane antigen (MA) complex. Eighty-two sera were tested on ELISA plates containing either both of the glycoproteins or each one separately. These included 45 IgA antibody-positive sera from patients with nasopharyngeal carcinoma (NPC). With these sera, there was a good correlation, both qualitatively and quantitatively, between results with the immunofluorescence (IF) and ELISA procedures. Although most IgA antibody-positive sera contained antibodies reactive with both gp125 and gp250/200, a number of sera contained antibodies reactive with one of the glycoproteins but not with both. The data indicated that both of these glycoproteins should be used in assays for detecting IgA antibodies to EBV, to avoid false-negative results. This assay should be useful for screening large populations for IgA antibodies to EBV and also possibly for monitoring disease course in patients with NPC.     

A comparison of rapid-healing prosthetic arterial grafts and autogenous veins.

The patency rates and healing characteristics during a nine-month period of internal velour Dacron grafts, external velour Dacron grafts, and Sparks-Mandril grown grafts were compared with autogenous jugular veins when used to bypass short segments of the canine femoral artery. Graft thrombosis occurred in three of 11 external velour grafts, in six of 11 internal velour grafts, and in three of 11 Sparks-Mandril grafts, None of 33 autogenous veins occluded. Graft thrombosis was not correlated with the degree of graft healing but rather with a hyperplastic proliferative intimal lesion observed at the proximal anastomosis of the occluded grafts.     

Assessment of hemodialysis adequacy by ionic dialysance: comparison to standard method of urea removal

BACKGROUND: The hemodialysis adequacy is one of the most important issues influencing the survival of patients on maintenance hemodialysis (HD). Assessment of measuring the delivered dialysis dose using clearance x time/volume (Kt/V) index requires multiple blood sampling. New methods for assessment of dialysis dose based on ionic dialysance (ID) have been suggested. Online conductivity monitoring (using sodium flux as a surrogate for urea) allows the repeated noninvasive measurement of Kt/V on each HD treatment. In this study we have compared this method with the standard method of estimating Kt/V. METHODS: We studied 24 established HD patients over a 4 week time period. Patients were dialyzed using Fresenius 4008S dialysis monitors, equipped with modules to measure ID. Data were manually collected and analyzed using the appropriate statistical software. Urea removal (UR) was measured once a week by a two-pool calculation, estimating an eKt/V. RESULTS: The Kt/V measured by ID highly correlated with the one derived from the measurement of the UR (r=0.8959, p< 0.0001). The ID underestimated UR by the mean of 6%. The ID varied greatly within individual patients with a median of 1.29 +/- 0.22. If the eKt/V > or = 1.2 is considered adequate, 33% of the patients would have been inadequately dialyzed. The mean HD duration to achieve an adequate dialysis was 4 hours and 47 minutes with high interpatient variability. CONCLUSION: The ID seems to be an easily obtained measure of the delivered dialysis dose, correlating well with standard UR method. Substantial individual variations imply that repeated measures (ideally for all treatments) are necessary to obtain a real answer to the mean treatment dose being delivered to the patients.     

Implementation of a Web- and simulation-based curriculum to ease the transition from medical school to surgical internship

BACKGROUND: Starting a surgical internship is a stressful experience. We developed a web and simulation-based curriculum to ease this transition. METHODS: We created an educational website containing a curriculum of commonly encountered on call situations. After match day in 2003, we contacted all of our new surgical interns. We performed a confidence assessment using a Likert-scale questionnaire, and the trainees were given access to the curriculum. In June 2003, we performed human patient simulator sessions. The participants were asked to provide feedback regarding the simulator experience. During the first week of residency, they were again asked to answer the confidence questionnaire. RESULTS: Sixteen residents (94%) used the web curriculum, and 17 (100%) participated in the simulations. Eleven (65%) filled out both questionnaires. The confidence score improved from 5.4 to 6.7 (P < .0001). CONCLUSIONS: A web and simulation-based curriculum for incoming house staff is feasible. Studies are underway to validate this novel method and to expand its use for surgical education.     

Mechanism of atrial flutter occurring late after orthotopic heart transplantation with atrio-atrial anastomosis

OBJECTIVE: We sought to better define the electrophysiologic mechanism of atrial flutter in patients after heart transplantation. BACKGROUND: Atrial flutter is a recognized problem in the post-cardiac transplant population. The electrophysiologic basis of atrial flutter in this patient population is not completely understood. METHODS: Six patients with cardiac allografts and symptoms related to recurrent atrial flutter underwent diagnostic electrophysiologic study with electroanatomic mapping and radiofrequency catheter ablation. Comparison was made with a control non-transplant population of 11 patients with typical counterclockwise right atrial flutter. RESULTS: In each case, mapping showed typical counterclockwise activation of the donor-derived portion of the right atrium, with concealed entrainment shown upon pacing in the cavotricuspid isthmus (CTI). The anastomotic suture line of the atrio-atrial anastomosis formed the posterior barrier of the reentrant circuit. Ablation of the electrically active, donor-derived portion of the CTI was sufficient to terminate atrial flutter and render it noninducible. Comparison with the control population showed that the electrically active portion of the CTI was significantly shorter in patients with transplant-associated flutter and that ablation was accomplished with the same or fewer radiofrequency lesions. CONCLUSIONS: Atrial flutter in cardiac transplant recipients is a form of typical counterclockwise, isthmus-dependent flutter in which the atrio-atrial anastomotic suture line forms the posterior barrier of the reentrant circuit. Ablation in the donor-derived portion of the CTI is sufficient to create bidirectional conduction block and eliminate this arrhythmia. Ablation or surgical division of the donor CTI at the time of transplantation could prevent this arrhythmia.