Victoria Price

Imatinib mesylate: An attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans

To document the clinical activity of imatinib mesyalte in a child with a dermatofibrosarcoma protuberans (DFSP). An 18‐month‐old girl presented with a large extremity DFSP. As surgical resection would have caused unacceptable functional defects, imatinib mesylate was administered to induce tumor reduction and or stabilization. After 23 weeks of therapy, magnetic resonance imaging (MRI) of the tumor showed a reduction in the subcutaneous thickness in the transverse plane. The drug was tolerated well without any adverse reactions. Imatinib mesylate offers a non‐surgical alternative for the treatment of large DFSP in children.

The prevention and treatment of bacterial infections in children with asplenia or hyposplenia: Practice considerations at the Hospital for Sick Children, Toronto

Children born without a spleen or who have impaired splenic function, due to disease or splenectomy, are at significantly increased risk of life‐threatening bacterial sepsis. The mainstays of prevention are education, immunization, and prophylactic antibiotics. The availability of conjugate 7‐valent pneumococcal vaccines for use in children to age 9 years at least, as well as conjugate meningococcal C vaccine in some countries, for use beginning in infancy, appear to represent beneficial additions, but not substitutions, to previous recommendations for the use of polysaccharide 23‐valent pneumococcal and quadrivalent A, C, Y, W‐135 vaccines. Routine immunization against H. influenzae type b should continue with non‐immunized children older than age 5 years receiving two doses 2 months apart, similar to children who have not previously received conjugate pneumococcal vaccine in infancy. Annual influenza immunization, which reduces the risk of secondary bacterial infection, is also recommended for asplenic children and their household contacts. Many experts continue prophylaxis indefinitely although prophylaxis of the penicillin allergic child remains suboptimal.

Clinical and molecular characteristics of pediatric gastrointestinal stromal tumors (GISTs).

To describe the clinical characteristics, molecular features, treatment, and outcome of six pediatric patients with gastrointestinal stromal tumors (GISTs).

The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase

Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Childrens Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.

Childhood chronic immune thrombocytopenic purpura: unresolved issues.

Chronic immune thrombocytopenic purpura (ITP), defined as a platelet count of below 150 × 109/L persisting for more than 6 months from onset of illness, occurs in approximately 20% to 25% of children with acute-onset ITP. A small subset of these patients (approximately 5%) will manifest symptomatic, severe thrombocytopenia (platelet counts <20 × 109/L) at 1 year or longer following diagnosis, and may require splenectomy. Complete/partial response rates following splenectomy in children with primary chronic ITP are of the order of 70% to 75%; response rates are lower in children with secondary ITP and those with complex autoimmune cytopenias (e.g., Evans syndrome). Laparoscopic splenectomy is increasingly preferred over open splenectomy. Patients should be immunized with the pneumococcal, Haemophilus type b and meningococcal vaccines before splenectomy; the duration of postsplenectomy antibiotic prophylaxis using penicillin or an equivalent antibiotic is controversial but should be at least until 5 years of age and for a minimum of 1 year postsplenectomy. Some experts advocate life-long antibiotic prophylaxis. Treatment of postsplenectomy failures is a challenge; partial/complete remission rates are low, and multimodality therapy may be more efficacious than monotherapy. The presence of an accessory spleen should be sought and removal considered if present. The role of newer treatment modalities such as anti-CD 20 remains to be established.

A comparative study on the effects of brotizolam and flurazepam on sleep and performance in the elderly.

This study was undertaken to compare the effects of 0.25 mg of brotizolam, 15 mg of flurazepam, and placebo on the sleep and performance of elderly subjects with chronic insomnia during a 2-week period of administration. Thirty-six male and female subjects who ranged in age from 60-72 years were divided into three treatment groups. All groups received placebo on the first three study nights, the active drug or placebo on the next 14 nights, and placebo again on the two following withdrawal nights. Sleep was assessed by means of questionnaires, and residual effects during the day were studied by means of the multiple sleep latency test and a variety of memory, performance, and vigilance tests. Sleep improved with all treatments. Rebound insomnia was noted on brotizolam withdrawal; flurazepam withdrawal had a milder impact. At the end of this 19-night study, only the placebo-treated group was sleeping significantly longer than at baseline. Both drug treatments increased daytime sleepiness and impaired performance on the first day after their administration. These effects waned after 2 weeks of treatment with brotizolam, but not flurazepam. The results of this study affirm the increased sensitivity of elderly subjects to benzodiazepine hypnotics and their indication for acute or intermittent insomnia, rather than for the more chronic forms of this disorder.

A Comparative 25‐Night Sleep Laboratory Study on the Effects of Quazepam and Triazolam on Chronic Insomniacs

Abstract: The short‐ and intermediate‐term actions, as well as the carryover and withdrawal effects, of quazepam, a new benzodiazepine hypnotic with a half‐life of 60 to 100 hours, were compared with those of triazolam, a triazolodiazepine hypnotic with a half‐life of 2 to 3 hours. Both the subjective effects of these drugs as well as their objective actions on the sleep EEG were sought. The study was conducted on two groups of six subjects with chronic insomnia who ranged in age from 32 to 56 years. Each subject was studied for 25 consecutive nights. Placebo was administered at bedtime on the first four nights, followed by 30 mg quazepam or 0.5 mg triazolam on the next 14 nights and by placebo again on the ensuing seven withdrawal nights. Both drugs increased the total sleep time during their administration and improved the subjective quality of sleep. Major differences, however, were observed on withdrawal. A significant and marked decrease in the total sleep time occurred with triazolam on the first withdrawal night. With quazepam, rebound insomnia was not observed at any time during the seven‐day withdrawal period.

Manganese Toxicity in a Child With Iron Deficiency and Polycythemia

A previously healthy 5-year-old girl presented with pica, emotional lability, and marked gait abnormalities. She had concurrent severe iron deficiency and polycythemia. Her magnetic resonance imaging (MRI) scan showed increased signal in the basal ganglia on T1-weighted images consistent with manganese neurotoxicity. Manganism was subsequently confirmed as her blood manganese levels were extremely elevated. Chelation therapy resulted in improvement in her mobility but she continues to have significant gait impairment. An epidemiological investigation identified well water as the potential source of manganese exposure for our patient, but to date, we have been unable to identify the nature of her neurotoxic susceptibility.

Inherited platelet disorders: a clinical approach to diagnosis and management

Inherited platelet disorders encompass a heterogeneous group of bleeding disorders where a variety of molecular defects can affect platelet number, function or both. The defects involve deficiencies or dysfunction of platelet receptors, signaling pathways, cytoskeletal proteins, granule contents and abnormalities in procoagulant activity. These disorders can be difficult to distinguish clinically as they present with the common symptom of mucocutaneous bleeding. Inherited thrombocytopenia needs to be considered in all patients suspected of having primary immune thrombocytopenia, where platelets may also have functional defects. After a careful history and physical examination, initial investigations include a complete blood count with a peripheral smear, followed by appropriate specific investigations that often require specialized referral centers. This article is a summary of the current data on clinical presentation, pathogenesis, diagnosis and management of inherited platelet disorders.

Chronic immune thrombocytopenic purpura in children: a survey of the canadian experience.

Background Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10-year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP. Results Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2±4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up. Conclusions The results from this study are consistent with published reports.