Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial.

Twenty-five patients with primary presentation of malignant astrocytoma, astrocytoma with anaplastic foci, and glioblastoma multiforme were treated with surgical resection and definitive radiation therapy followed by intravenous or intra-arterial administration of Iodine-125 labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The patients presented with primary untreated disease, positive contrast enhanced computed tomography scans of the brain, and compatible clinical symptoms. In this Phase II clinical trial, the patients had surgical debulking or biopsy followed by definitively administered external beam radiation therapy and one or multiple doses (35 to 90 mCi per infusion) of radiolabeled antibody. The total cumulative doses ranged from 40 to 224 mCi. The administrations of the radiolabeled antibody were performed in most cases 4-6 weeks following completion of the primary surgery and radiation therapy. Ten patients had astrocytoma with anaplastic foci and 15 had glioblastoma multiforme. No significant life-threatening toxicities were observed during this trial. At 1 year 60% of the patients with astrocytoma with anaplastic foci or glioblastoma multiforme are alive. The median survival for both groups was 15.6 months.     

Perioperative specific management of blood volume loss in craniosynostosis surgery

Accurate assessment and replacement of blood loss and fluid–electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg^–1 h^–1 except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis. Received: 16 February 1998     

Central Nervous System Lymphomatoid Granulomatosis Presenting with Parkinsonism

Lymphomatoid granulomatosis (LG) is a potentially malignant lymphoproliferative disorder. The lung is the most common involved site, followed by the skin and nervous system. However, LG of the central nervous system presenting with Parkinsonism is very rare. We report a patient with LG who presented with parkinsonian features such as bilateral rigidity, bradykinesia, and agitation. Brain magnetic resonance imaging showed multifocal punctuate enhanced lesions in both supra- and infratentorial areas. Steroid pulse therapy resulted in a dramatical improvement in the symptoms and MRI abnormalities.     

Fidgetin-like 1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts.

The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation.     

Fontan conversion with arrhythmia surgery.

OBJECTIVE: Hemodynamic abnormalities and refractory atrial arrhythmias in patients late after the Fontan operation result in significant morbidity and mortality. We reviewed our experience with Fontan conversion and concomitant arrhythmia surgery. METHODS: Between January 1996 and February 2004, 16 patients underwent Fontan conversion and arrhythmia surgery. Mean age at the initial Fontan operation was 5.1+/-3.5 (range: 2-15) years and mean age at Fontan conversion was 17.0+/-5.8 (range: 6-30). The initial Fontan operations were atriopulmonary connections in 14 patients, extracardiac lateral tunnel in 1, and intracardiac lateral tunnel in 1. The types of arrhythmia included atrial flutter in 10 patients and atrial fibrillation in 3. Fontan conversion operation was performed with intracardiac lateral tunnel in 5 patients and extracardiac conduit in 11. Arrhythmia surgery included isthmus cryoablation in 10 patients and right-sided maze in 3. RESULTS: There has been no mortality. At Fontan conversion operation, 7 patients required permanent pacemaker. All patients have improved to New York Heart Association class I or II. With a mean follow-up of 26.9+/-30.6 (range:1-87) months, 16 patients had sinus rhythm, 2 patients had transient atrial flutter which was well controlled, and 2 patients required permanent pacemaker during follow-up. CONCLUSIONS: Fontan conversion with concomitant arrhythmia surgery and permanent pacemaker placement is safe, improves New York Heart Association functional class, and has a low incidence of recurrent arrhythmias. In most patients, concomitant permanent pacemakers are needed.     

The effect of skin surface warming during anesthesia preparation on preventing redistribution hypothermia in the early operative period of off-pump coronary artery bypass surgery.

OBJECTIVE: Redistribution hypothermia adversely affects hemodynamics and postoperative recovery in patients undergoing cardiac surgery. In off-pump coronary bypass surgery (OPCAB), maintaining the temperature is important because warming by cardiopulmonary bypass is omitted. Pre-warming studies reported earlier showing pre-warming as an effective means of preventing redistribution hypothermia was time consuming since it required at least 1-2h to pre-warm the patients before the surgery. Because pre-warming for such a long time is impractical in clinical practice, this study evaluated the efficacy of active warming during the preanesthetic period for the prevention of redistribution hypothermia in the early operative period of OPCAB. METHODS: After gaining the approval of Institutional Review Board and informed consent from the patients, 40 patients undergoing OPCAB were divided into control and pre-warming groups. The patients in control group (n=20) were managed with warm mattresses and cotton blankets, whereas patients in pre-warming group (n=20) were actively warmed with a forced-air warming device before the induction of anesthesia. Hemodynamic variables and temperature were recorded before anesthesia (Tpre) and at 30 min intervals after anesthesia for 90 min (T30, T60, and T90). RESULTS: Active warming duration was 49.7+/-9.9 min. There were no statistically significant differences in skin temperature, core temperature and hemodynamic variables between the two groups at preinduction period except for mean arterial pressure and central venous pressure. The core temperature at T30, T60, and T90 was statistically higher in pre-warming group than that in control group. Core temperature of six (30%) and seven patients (35%) in control group was reduced below 35 degrees C at T60 and T90, respectively, whereas core temperature of only one patient (5%) in pre-warming group was reduced below 35 degrees C at T90 (P=0.02). CONCLUSIONS: Active warming using forced air blanket before the induction of anesthesia reduced the incidence and degree of redistribution hypothermia in patients undergoing OPCAB. It is a simple method with reasonable cost, which does not delay the induction of anesthesia nor the surgery.     

A quantitative analysis of valgus torque on the ACL: a human cadaveric study.

The loads needed to elicit a positive pivot shift test in a knee with an anterior cruciate ligament (ACL) rupture have not been quantified. The coupled anterior tibial translation (ATT), coupled internal tibial rotation (ITR), and the in situ force in the ACL in response to a valgus torque, an inherent component of the pivot shift test, were measured in 10 human cadaveric knee specimens. Using a robotic/universal force-moment sensor testing system, valgus torques ranging from 0.0 to 10.0 Nm were applied in nine increments on the intact and ACL-deficient knee in flexion ranging from 0 degrees to 90 degrees. At 15 degrees of knee flexion, the coupled ATT and ITR were significantly increased in the ACL-deficient knee when compared to the intact knee. Coupled ATT increased a maximum of 291% (6.7 mm, p<0.05), while coupled ITR increased a maximum of 85% (5.1 degrees, p<0.05). At 30 degrees, the increases in coupled ATT and ITR were significant at valgus loads of 3.3 Nm and greater with a maximum increase in coupled ATT of 137% (6.3 mm, p<0.05) and a maximum increase in coupled ITR of 38% (3.6 degrees, p<0.05). At 45 degrees, coupled ATT increased significantly (maximum of 69%, 4.4 mm, p<0.05), but only at torques > or =6.7 Nm. The in situ force in the ACL was less than 20 N for all flexion angles when a torque between 3.3 and 5.0 Nm was applied. Low valgus torque elicited tibial subluxation in the ACL-deficient knee with low in situ ACL forces, similar to a positive pivot shift test. Thus, application of a valgus torque may be suitable to evaluate ACL-deficient and ACL-reconstructed knees, since subluxation can be achieved with minimal harm to the ACL graft. This work is important in understanding one load component needed for the pivot shift examination; further studies quantifying other load components are essential for better comprehension of the in vivo pivot shift examination.