Total anomalous pulmonary venous drainage beyond childhood

We studied the anatomic characteristics and results of surgery in 27 patients with total anomalous pulmonary venous drainage who were 15 years or older between January 1997 and July 2007. Mean age was 19.7+/-11.6 years (15-48 years). The anatomic subtypes were supracardiac (n=15), cardiac (n=7), and mixed (n=5). Fourteen patients were in NYHA class II and 13 were in NYHA class III. Eleven patients had severe and the rest had moderate pulmonary arterial hypertension; six patients had significant right ventricular dysfunction. All patients underwent complete repair. A small inter-atrial communication was left open in four patients and in two patients, a fenestrated unidirectional valved patch was used to close the atrial septal defect. There were no early or late deaths. Follow-up was 3-127 months (mean 61.2+/-36.1 months). Twenty patients were in NYHA class I and seven were in class II. Echocardiography showed normal right and left ventricular function in all patients with reduction of pulmonary arterial pressures in 26 patients. One patient underwent radiofrequency ablation for new onset atrial flutter. Surgery can be safely undertaken in a few naturally selected group of patients with total anomalous pulmonary venous drainage who survive beyond childhood.     

A4T mutation in the SOD1 gene causing familial amyotrophic lateral sclerosis

We report the clinical and laboratory findings in the largest kindred so far recorded with familial amyotrophic lateral sclerosis due to an A4T mutation in the SOD1 gene. The age of onset ranged from 32 to 60 years, with a mean of 46 years. Weakness in the legs was the most frequent early symptom and there was a predominance of lower motor neuron signs. The mean time from onset of symptoms to death was 14 months. One man with onset at the age of 37 has shown a slowly developing form and is currently alive 76 months after diagnosis (October 2002), although severely affected. The A4T mutation, with one exception, was of similar severity to the A4V mutation.     

Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients

BackgroundTumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS.Patients and MethodsWe planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration.ResultsFifty-five patients were recruited for this study. Pediatric patients (< 18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P < .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose.ConclusionSingle-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.     

Aneurysm of the vein of galen in neonates: report of four cases.

In neonates, aneurysm of the vein of Galen often masquerades as cyanotic congenital heart disease. We report 4 cases of neonates presenting with malformation of the vein of Galen at our insititution. An increased awareness of this entity seems warranted.     

Stimulation of tyrosine phosphorylation after ligation of beta7 and beta1 integrins on human B cells

B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to beta1 integrins, predominantly alpha4 beta1, mature B cells also express alpha4 beta7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal address in cell adhesion molecule-1. Here we describe that crosslinking of alpha4 beta7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105-130 kD, indicating that beta7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of alpha4 beta1. Interestingly, ligation of alpha5 beta1 or alpha6 beta1 also stimulated the 105-125 kD group of phosphorylated proteins, whereas ligation of beta2 integrins did not. The focal adhesion tyrosine kinase p125FAK was identified as one of these substrates. Beta1 or beta7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins.     

Heterotypic adherence between human B-lymphoblastic and pre-B- lymphoblastic cells and marrow stromal cells is a biphasic event: integrin very late antigen-4 alpha mediates only the early phase of the heterotypic adhesion

Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells is essential for normal lymphopoiesis and malignant lymphoblastic development. However, the detailed molecular mechanisms by which this heterotypic adherence occurs are poorly understood. The cell-cell interactions between a B-lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were chosen as models to investigate potential mechanisms and adhesion molecules involved in the apposition between normal and malignant lymphoblastic cells and MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled with monoclonal antibody (MoAb) blocking experiments, were used to quantify the attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for variable time periods, ranging from 1 minute to 4 hours. Results from the temporal study suggest that the heterotypic adherence of the B-lymphoblastic cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1 minute) after the two cells come into contact. More specifically, the early phase of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell adhesion molecule 1 (VCAM- 1) interactions, as evidenced by the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which suggests the possible involvement of other adhesion molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may be important in homing of the malignant lymphoblastic cells to the MSC and the late phase in retention of malignant lymphoblastic cells in the bone marrow.     

Successful treatment of calcific uremic arteriolopathy with sodium thiosulfate in a renal transplant recipient

Abstract Calcific uremic arteriolopathy (CUA) is a rare but life-threatening disorder of arteriolar calcification. It frequently leads to severe ischemia, intense pain, and tissue necrosis with non-healing skin ulcerations. CUA usually occurs in patients with chronic kidney disease (CKD), especially those on dialysis, and its occurrence is rare in kidney transplant recipients. The treatment of this disorder is not clearly defined, and no randomized prospective trials are available. Treatment has focused on optimizing dialysis treatment, control of bone mineral parameters, wound care, experimental anticalcification therapies-using bisphosphonates, cinacalcet, parathyroidectomy, and hyperbaric oxygen. Such treatments are based on the pathophysiological considerations and evidences from case reports or series. Recently, several cases have reported about the emerging benefits of intravenous sodium thiosulfate (STS) in the treatment of CUA. STS has resulted in rapid pain relief, wound healing, and prevention of death. We report a case of CUA in a 63-year-old Caucasian man with a functioning renal allograft. In this patient, intravenous STS was administered for 8 months, which was the principal therapy, which resulted in complete resolution of the CUA and skin healing.