Patient- and caregiver-reported bleeding symptoms and reasons for starting and stopping treatment with recombinant factor VIIa: analysis of the Dosing Observational Study in Haemophilia (DOSE).

Acute haemorrhage treatment in patients with congenital haemophilia with inhibitors (CHwI) has transitioned to home. Patient/caregiver perceptions of bleeding symptoms and reasons for starting/stopping treatment were investigated. Frequently bleeding CHwI patients (≥ 4 episodes in 3 months) prescribed recombinant factor VIIa (rFVIIa) as first-line therapy, or their caregivers, completed daily diaries for 3-6 months capturing bleeding symptoms and treatment decisions. Thirty-eight patients reported 131 joint, 19 muscle and 44 other bleeding events. Symptoms (all/joint/muscle haemorrhages) included pain (78.9%/90.1%/89.5%), joint swelling (44.8%/65.6%/5.3%), decreased mobility (41.2%/48.9%/68.4%), local warmth (21.1%/26.0%/15.8%), other swelling (16.0%/6.9%/47.4%), irritability (14.9%/16.8%/10.5%), visible bleeding (12.4%/7.6%/5.3%) and redness (10.3%/6.1%/10.5%). Most patients/caregivers recognized when bleeds started (58.4%/58.0%), but were less clear when bleeds stopped (43.5%/33.3%). Medication was commonly started by patients/caregivers when bleeds were identified (73.7%/47.4%) or when concerned bleeds might start (32.9%/27.6%). Common reasons for delays in starting medication by patients included 'I thought it might not be a bleed' (48.9%), 'I wanted to see if the bleed progressed' (46.8%) and 'I thought it was just joint pain' (44.7%). Common reasons for caregivers were: 'I wanted to see if it progressed' (37.9%), 'I didn't have medication' (20.7%) and 'I thought it might not be a bleed' (17.2%). Reasons for stopping medication for patients/caregivers were pain cessation/stabilization (93.9%/54.7%), arrest of swelling progression (60.6%/46.9%) and improved mobility (50.0%/35.9%). Patients/caregivers have difficulty in determining bleed onset and particularly resolution, both quite necessary for treatment decisions and clinical trials. Caregivers' inability to assess resolution in children may lead to longer treatment duration seen in the Dosing Observational Study in Haemophilia (DOSE).

Intravenous anesthesia with propofol for painful procedures in children with cancer.

OBJECTIVE: To study the safety and efficacy of propofol-based intravenous anesthesia in children with cancer undergoing painful procedures. METHODS: This study is a retrospective analysis of data collected from 52 consecutive children who underwent 335 procedures using propofol anesthesia. These data were routinely collected in all patients: time to induction, duration of the procedure, time to recover, and the doses of the drugs used. Monitoring with electrocardiography and pulse oximetry was continuous during the procedure; blood pressures were recorded before and after the procedure and every 5 to 10 minutes during the procedure. The patients received one of these four propofol-based intravenous regimens according to the anesthesiologist's preference: propofol only; propofol plus fentanyl; propofol plus midazolam; or propofol, fentanyl, and midazolam. The efficacy of sedation was rated by this scoring system: 3 = no movement during procedure; 2 = minimal movement that did not interfere with the procedure; 1 = moderate movement requiring physical restraint to complete the procedure. RESULTS: There were six episodes of mild hypoxia (oxygen saturation 85%-94%) and one episode of laryngospasm. None required intubation. Two patients had agitation and one patient had emesis during the postrecovery phase. There was no difference in the efficacy of sedation between the four regimens. Patients receiving the combination of propofol, fentanyl, and midazolam received the least amount of propofol and required the least time to recover. There were no life-threatening complications. CONCLUSIONS: Propofol-based anesthesia, when administered by an anesthesiologist in a controlled setting, is safe and effective for performing painful procedures in children with cancer.

Intravenous anti-D immune globulin-induced intravascular hemolysis in Epstein-Barr virus-related thrombocytopenia.

RhoD immune globulin intravenous (anti-D IGIV) increases platelet counts in patients who have not undergone splenectomy and are positive for RhoD with idiopathic thrombocytopenic purpura. After treatment, in most patients, anemia develops as a result of immune-mediated red cell destruction in the spleen. Although intravascular hemolysis (IVH) is not expected, life-threatening IVH has been recently reported by the Food and Drug Administration, and physicians are encouraged to report their experience with patients with idiopathic thrombocytopenic purpura in whom IVH develops after anti-D administration. Severe IVH was observed after treatment with anti-D IGIV in two adolescent girls with acute thrombocytopenia related to Epstein-Barr virus. They did not have hemolytic anemia before treatment. The authors believe that anti-D IGIV triggered an unusual virus-induced immune response causing hemolysis; therefore, anti-D IGIV should not be used in patients with Epstein-Barr virus-related thrombocytopenia, particularly during the acute phase of infection.

Corticosteroid prophylaxis for neurologic complications of intravenous immunoglobulin G therapy in childhood immune thrombocytopenic purpura.

To assess in a retrospective analysis if there is evidence suggesting corticosteroids can prevent the neurologic complications of intravenous immunoglobulin (IVIG) therapy in children with immune thrombocytopenic purpura (ITP). From March 1985 to September 1997, 112 children received IVIG (1 g/kg/day for one or two dosages) for the treatment of ITP. During the years 1990 to 1997, 23 children nonrandomly received a short course of prednisone (2 mg/kg/day during and for 3 days after the completion of IVIG therapy) as a prophylaxis against the neurologic complications of IVIG therapy. The authors analyzed the data of all 112 children and compared the incidence of neurologic complications in those who received prednisone prophylaxis with those who did not. The severity of the complications was assessed as follows: grade 1, headache only; grade 2, headache plus vomiting; grade 3, headache, vomiting, and fever; grade 4, headache, vomiting, fever, and meningeal signs (aseptic meningitis). Of the 23 children who received prednisone prophylaxis, 2 (8.7%) experienced headache and vomiting after the completion of prednisone prophylaxis. Of the 89 children without prednisone prophylaxis, 27 (30.3%) experienced neurologic symptoms of varying severity, including one patient with aseptic meningitis proven by examination of the spinal fluid. Twelve of these patients needed additional hospital care for the complications. Children receiving prednisone had a 78% lower risk of neurologic complications (OR = 0.22; CI = 0.05-0.90; P = 0.036). This retrospective study shows a short course of prednisone therapy, given during and until 3 days after the completion of IVIG infusion, is likely to decrease the incidence and severity of neurologic complications of IVIG in children with ITP.

T-cell acute lymphoblastic leukemia after renal transplantation in childhood.

PURPOSE: Lymphoproliferative disorders in solid organ recipients are usually of B-cell type and have rarely been described in childhood. This study describes the development of T-cell acute lymphoblastic leukemia (ALL) in a child occurring 6 years after renal transplantation. PATIENT: An 11-year-old boy had received a renal allograft from his father at 5 years of age. He was receiving imuran, prednisone, and cyclosporin A prophylaxis for graft rejection after transplant until T-cell ALL was diagnosed. Although an acute Epstein-Barr virus (EBV) infection was noted at the time of diagnosis, the EBV genome was not detected by Southern blot analysis and polymerase chain reaction (PCR) in the leukemic cells. RESULTS: A large mediastinal mass and malignant pleural effusion were noted at diagnosis. Leukemic cells of his bone marrow and pleural fluid expressed T-cell antigens with unique cytogenetic features, including add(1)(p36.1), del(11)(q14), and monosomy 7. EBV serology was consistent with a recent infection but EBV genome was not detected by Southern blot and PCR analysis in his leukemic cells. Human T-lymphotropic virus-I (HTLV-I) antibody titer was negative. He has been on chemotherapy for 9 months, maintaining his first remission. CONCLUSIONS: Malignancies developing after renal transplantations are usually lymphoproliferative disorders and of B-cell origin. In the majority of these patients, EBV plays an etiologic role. Although adult T-cell leukemia developing during immunosuppressive treatment in renal transplant recipients has been reported, T-cell leukemia after transplant in pediatric patients has not been reported to date. This case is unique in terms of the patient's age, the T-cell immunophenotype, the cytogenetic features, and the absence of an EBV genome within the leukemic cells despite an acute EBV infection before diagnosis.

Infections due to nontuberculous mycobacteria in children with leukemia.

We reviewed the spectrum of infections due to nontuberculous mycobacteria (NTM) in children with leukemia. Three children acquired such infections. One patient developed pneumonia after the cessation of chemotherapy when Mycobacterium xenopi was identified in his lung biopsy specimen. He required 2 years of treatment with antituberculous agents and clarithromycin. Cultures of central and peripheral blood specimens from two patients yielded Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Broviac catheters were likely the source of infection. Removal of the catheters and antibiotic treatment resulted in cure. Central venous catheters in leukemic children are potential sources of infection. For febrile neutropenic children with leukemia who do not respond to antibiotic therapy, cultures positive for diphtheroids or negative routine bacterial and fungal cultures should raise a suspicion for infections due to NTM. Systemic infections may require up to 2 years of therapy. Removal of the infected catheters during persistent or recurrent infections in necessary for control of the infection.

Solid variant of aneurysmal bone cyst in a patient with cyclic neutropenia.

A 16-year-old female with cyclic neutropenia (CN) was incidentally found to have a thoracic vertebral mass during the preoperative work-up for maxillary sinus surgery. An exploratory thoracotomy revealed a very vascular tumor involving T-10 and T-11 vertebral bodies. Gross total resection of the tumor was achieved. Pathology revealed a solid variant of aneurysmal bone cyst. This is a rare benign neoplasm of bone more commonly seen in the mandible and facial bones as well as involving the small tubular bones of the hands and feet. Because of its rarity, location, and an unknown association with CN, we found this case worthwhile to publish.

Langerhans cell histiocytosis associated with partial DiGeorge syndrome in a newborn.

PURPOSE: We report the unrecognized association of Langerhans cell histiocytosis (LCH) with partial DiGeorge syndrome. PATIENT AND METHODS: A 7-week-old infant with endocrine and immunologic characteristics of DiGeorge syndrome displayed multisystem involvement of Letterer-Siwe disease at birth. RESULTS: Despite vigorous medical support and chemotherapy, she died at 9 months of age with multisystem failure. CONCLUSIONS: This case supports the role of the thymus n the pathogenesis of LCH.

Oxalate accumulation in rat renal cortical slices.

Tubular transport of oxalate is thought to be an energy-mediated process which may contribute to the renal deposition of calcium oxalate in a variety of pathologic states. In order to examine this possibility, the renal handling of oxalate was investigated in rat renal cortical slices in vitro. Slices incubated in vitro with 1 microM [14C]oxalate in Krebs-Ringer bicarbonate buffer at 25 degrees C for 180 min achieved a mean slice to medium ratio of 2.8 +/- 0.08 (SEM) and a mean tissue concentration of 7.7 +/- 0.2 mumol/kg dry wt (N = 64). Section freeze-dry autoradiographs demonstrated maximum uptake within proximal tubule cells but no crystals were evident. Substituting N2 for O2, adding KCN, or removing Ca2+ increased uptake of 14C-oxalate. Dinitrophenol (DNP) and iodoacetamide (IoAc), however, significantly decreased, and O degrees C eliminated slice uptake. Slices incubated with 100 microM [14C]oxalate showed a further increase in tissue accumulation and the appearance of [14C]oxalate crystals. Crystals formed in vitro were deposited throughout the tissue. Oxalic acid did not appear to share the organic acid by renal cortical slices in vitro is largely independent of energy-mediated mechanisms.