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Biomedical subjects

John Wu

Publications and source records attributed to John Wu.

13 recordsLinked to original sources

Chinese norms of McNamara's cephalometric analysis.

OBJECTIVE: To establish cephalometric norms of McNamara's analysis in young Chinese and compare them to those of a matched young Caucasian sample. MATERIALS AND METHODS: The material comprised lateral cephalometric radiographs of a random sample of 200 male and 205 female 12-year-old southern Chinese children, and an additional sample of 43 male and 43 female 12-year-old British Caucasian children in Hong Kong. The radiographs were digitized twice with the CASSOS program. RESULTS: The results showed that there were statistically significant gender differences for six out of the 11 cephalometric variables in the Chinese, but for only one variable in the Caucasians. The size of the statistically significant gender differences varied from -0.3 to 0.4 on SD scores. There were statistically significant ethnic differences for eight variables in males and seven variables in females. The size of the observed statistically significant ethnic differences varied from -1.8 to 1.6 on SD scores. CONCLUSION: The use of specific standards for Chinese, separate for gender, for McNamara's cephalometric analysis seems to be justified.

Asian People↗

Comparison of the anticoagulant effect of a direct thrombin inhibitor and a low molecular weight heparin in an acquired antithrombin deficiency in children with acute lymphoblastic leukaemia treated with L-asparaginase: an in vitro study.

Thrombosis occurs in 37% of children with acute lymphoblastic leukaemia (ALL) and is related to an L-asparaginase-induced acquired antithrombin (AT) deficiency. The incidence dictates the need for anticoagulant prophylaxis. Direct thrombin inhibitors (DTI) are independent of AT for effect and may thus have advantages in this population. The objective of this study was to determine the interaction of an AT deficiency with the anticoagulant effects of a DTI and a low molecular weight heparin (LMWH). Plasma samples from children with ALL were pooled (mean AT 0.53 U/ml). LMWH 0.3 and 0.7 U/ml or melagatran 0.3 and 0.5 micromol/l were added to the pools, then divided and AT was added back to one aliquot. In additional experiments, AT was added to AT immuno-depleted plasma. Endogenous thrombin generation capacity (ETGC) was assessed by the continuous method. In plasma with LMWH, there was a 66-88% decrease in ETGC in AT-normalised samples compared with neat. Conversely, no significant difference in ETGC with or without AT added for melagatran was seen. Experiments with AT-depleted plasma showed no effect of AT level on anticoagulant activity of DTI, but a significant relationship for LMWH. By contrast to LMWH, DTI provides a consistent anticoagulant response independent of AT levels in children with AT deficiency.

Adolescent↗

Purification of transferrin from Cohn supernatant I using ion-exchange chromatography.

The present paper describes an anion-exchange chromatography method to separate iron-free apo-Tf (apo-transferrin) from albumin and IgG in Cohn supernatant I. The method uses DEAE-fast flow Sepharose chromatography along with optimized protein concentration (5%, w/v) and column operation conditions (40 g/l, conductivity <1.0 mS/cm) to resolve apo-Tf from IgG and albumin. The single step purifies apo-Tf to >90% and provides an efficient means to obtain commercial quantities of the protein.

Chemical Fractionation↗

A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study.

BACKGROUND: Thrombotic events (TEs) are serious secondary complications in children with acute lymphoblastic leukemia (ALL) who receive L-asparaginase (ASP) therapy; however, the prevalence of TEs has not been established. The primary objective of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study was to determine the prevalence of TEs. The secondary objective was to detect any association of TEs with the presence of congenital or acquired prothrombotic disorders. METHODS: Children with ALL were screened for TEs at the end of ASP treatment using bilateral venograms, ultrasound, magnetic resonance imaging, and echocardiography. Symptomatic TEs were confirmed by appropriate radiographic tests. All tests were read by a blinded central adjudication committee. RESULTS: Twenty-two of 60 children had TEs, a prevalence of 36.7% (95% confidence interval, 24.4-48.8%). TEs were located in the sinovenous system of the brain in 1 patient, the right atrium in 3 patients, and the upper central venous system in 19 patients. TEs detected by venography resulted in 1) 25-100% occlusion, with 1 in 3 patients showing occlusion of > 75% of the greatest vessel dimension, and 2) the presence of collaterals in 60% of patients, with 40% categorized as major. No children with TEs were positive for factor V Leiden or prothrombin gene 20201A, and four of eight children with antiphospholipid antibodies had a TE. CONCLUSIONS: The prevalence of TEs is exceedingly high in this population, and it is likely that the extent of occlusion is likely clinically significant. No trend was seen toward an association between TEs and the presence of congenital prothrombotic disorders. A trend was seen toward an association between TEs and antiphospholipid antibodies. Carefully designed clinical trials of primary prophylaxis for the prevention of TEs are required in this patient population.

Adolescent↗

Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin. Parametric and validation studies.

Caprylate has long been used as a stabiliser for albumin solutions, as well as a precipitation agent for immunoglobulins, ceruloplasmin and more recently in removing contaminants during albumin purification. Its virucidal properties have been explored and it has been proposed that the non-ionised form of the caprylate acid disrupts the integrity of the lipid bilayer and membrane associated proteins of enveloped viruses. The studies reported here further explore the use of this fatty acid to inactivate lipid-enveloped viruses in albumin manufactured for therapeutic use. Caprylate concentrations considered above solubility limits were adopted. Acidic pH was used to maximise the percentage of non-ionised caprylate and elevated temperatures were used to enhance inactivation rates. Parameters were manipulated to determine the relationship between pH, temperature and caprylate: protein ratio. These studies demonstrated that elevated temperature and low pH were critical in achieving significant reduction in virus infectivity and that the rate and extent of inactivation was sensitive to changes in caprylate:protein ratio and to changes in pH. Final inactivation conditions of 10% w/v protein, 16 mM caprylate, pH 4.5 and 30 degrees C were chosen to minimise protein dimerisation and to achieve greater than 4 log(10)inactivation of the most resistant virus tested, bovine viral diarrhoea virus. Validation studies using both model and relevant blood borne viruses demonstrated this to be a robust and effective viral inactivation step and is complementary to the commonly used pasteurisation viral inactivation step, thus providing an additional margin of safety to this valuable therapeutic blood product.

Animals↗

Chronic active Epstein-Barr virus infection associated with low expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) on natural killer cells.

Chronic active Epstein-Barr virus (CAEBV) infection is an uncommon and severe manifestation of EBV infection that frequently leads to the development of natural killer (NK) or T cell lymphomas. We report here that NK cells derived from a boy with CAEBV showed decreased cytotoxic function and impaired interferon-gamma secretion against a variety of transformed target cell lines. In addition, NK cells from the patient lacked expression of the broadly expressed NK receptor, leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). These data suggest that CAEBV is associated with low expression of LAIR-1 on NK cells.

Cells, Cultured↗

Development of disease-specific health-related quality-of-life instruments for children with immune thrombocytopenic purpura and their parents.

PURPOSE: Immune thrombopenic purpura (ITP) is an important childhood hematologic disorder that is often frightening to patients and their parents because of its acute onset and bleeding symptoms. There is no consensus on the management of ITP in children. Pediatric hematologists have differing management philosophies, yet most, explicitly or implicitly, incorporate into their management approach the potential impact on the child's and family's quality of life. There is no validated ITP-specific health-related quality-of-life instrument for use with children with ITP, nor is there one to evaluate the burden experienced by their parents. ITP is usually a self-limited disorder. With current controversy over management approaches, an evaluation of the disease burden experienced by the child and the family may assist with the assessment of alternative treatment approaches. METHODS: Using standard clinimetric methodology, 88 children with acute or chronic ITP, along with their parents, participated in the development of the instruments. RESULTS: The 26-item ITP-Child Quality-of-Life Questionnaire includes five domains: treatment side effect-related, intervention-related, disease-related, activity-related, and family-related. This instrument can be used as a self-completed instrument for most children older than 7 years or as a proxy-completed instrument by parents of children younger than 7 years. The 26-item ITP-Parental Burden Quality-of-Life Questionnaire includes six domains: concerns related to diagnosis/investigation, treatment/disease monitoring, monitoring of child's activities, interference with daily life, disease outcome, and emotional impacts. CONCLUSIONS: The first steps of the development of these formally developed instruments are complete. The instruments are available for study to validate and test their responsiveness through use in clinical research studies. Such instruments are increasingly recognized as important for comprehensive measurement of patient outcomes in this and other areas of pediatric hematology/oncology practice.

Adolescent↗

Spontaneous resolution of calvarial eosinophilic granuloma in children.

OBJECTIVE: The recommended treatment for solitary calvarial eosinophilic granuloma (EG) is surgical resection by curettage, craniectomy or craniotomy. The purpose of this study was to describe the spontaneous resolution of calvarial EG and discuss 'observation only' as an option in the management of this condition. METHODS: A retrospective review was performed of children with calvarial EG seen at a tertiary care children's hospital. Of a total of 17 such patients, four were managed without any intervention and formed the basis of this report. RESULTS: In all four patients treated by 'observation only', there was a tender calvarial mass which enlarged rapidly over a few days and then resolved slowly over many weeks. The diagnosis of EG was based on the findings of plain radiographs and/or computed tomography. All masses had resolved by 8 weeks, and the underlying cranial defect filled in spontaneously in all cases. There was no recurrence at follow-up, which ranged from 2 months to 7 years. CONCLUSIONS: 'Observation only' should be considered as a viable option in the management of children with solitary calvarial masses that have the radiographic features of EG. Consideration should be given to delaying surgical intervention to allow time to see if spontaneous resolution occurs.

Adolescent↗

Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study.

An association has been reported between thrombotic events and the use of L-asparaginase (ASP) in children with acute lymphoblastic leukaemia (ALL). The mechanism for thrombosis is likely related to an acquired antithrombin deficiency. Since a primary prophylaxis using antithrombin concentrates may prevent thrombosis, the PARKAA (Prophylactic Antithrombin replacement in kids with ALL treated with L-asparaginase) study was performed. The objectives of PARKAA were to determine if there was a trend to efficacy and safety of antithrombin treatment as assessed by 1) incidence of thrombosis 2) incidence of bleeding and 3) plasma markers of endogenous thrombin generation as surrogate outcomes for thrombosis. The study was not powered to answer the question of efficacy and safety, but rather to detect a trend. PARKAA was an open, randomised, controlled study in children with ALL being treated with ASP. Children were randomised to receive antithrombin infusions or no antithrombin treatment. All thrombotic events were confirmed using bilateral venography, ultrasound, echocardiography and MRI. The incidence of thrombosis in patients treated with antithrombin was 28% (95% CI 10-46%), compared to 37% (95% CI 24-49%) in the non treated arm. Two minor bleeds occurred in patients in the treated arm, but were not considered to be related to antithrombin. No significant differences were seen in plasma markers by the treatment group. In conclusion, treatment with antithrombin concentrate shows a trend to efficacy and safety. In contrast, there was no difference in surrogate markers for thrombosis. Carefully designed clinical trials are needed to test the efficacy and safety of antithrombin in this population.

Adolescent↗

Mycobacterium paratuberculosis in dairy herds in Alberta.

Fifty dairy herds in Alberta were tested for the presence of Mycobacterium paratuberculosis by fecal culture and serum enzyme linked immunosorbent assay (ELISA). Individual sera (1500) were tested for antibodies to M. paratuberculosis by ELISA. Fecal samples were combined in pools of 3 (10 pools/herd) for a total of 500 pools that were cultured for M. paratuberculosis. Thirty cultures, including all 10 pools from 1 herd, were not readable due to fungal contamination. The remaining 470 cultures, representing 49 herds, yielded 16 positive pools (3.4% +/- 2.1%) from 10 herds (20.4% +/- 11.3%). The ELISA of each of the 1500 sera detected 105 (7.0% +/- 2.4%) positive sera and 20 (40.0% +/- 13.6%) positive herds, based on 2 or more individual positive sera in the herd. The true herd-level prevalence, as determined by ELISA, was 26.8% +/- 9.6%. The true herd-level prevalence, as determined by M. paratuberculosis fecal culture, ranged from 27.6% +/- 6.5% to 57.1% +/- 8.3%, depending on whether 1, 2, or all 3 individual fecal samples in the positive fecal pool were culture positive.

Alberta↗

Comparison of venography and ultrasound for the diagnosis of asymptomatic deep vein thrombosis in the upper body in children: results of the PARKAA study. Prophylactic Antithrombin Replacement in Kids with ALL treated with Asparaginase.

Deep vein thrombosis (DVT) in children occurs primarily in the upper body venous system. This prospective diagnostic study compared bilateral venography and ultrasound for detection of DVT in the upper venous system in 66 children with acute lymphoblastic leukemia. Results were interpreted by central blinded adjudication. Deep venous thrombosis occurred in 29% (19/66) patients. While 15/19 DVT were detected by venography (sensitivity 79%), only 7/19 were detected by ultrasound (sensitivity 37%). The 12 DVT detected by venography but not by ultrasound were located in the subclavian vein or more central veins. Three of 4 DVT detected by ultrasound but not by venography were in the jugular vein. We conclude that ultrasound is insensitive for DVT in the central upper venous system but may be more sensitive than venography in the jugular veins. A combination of both venography and ultrasound is required for screening for DVT in the upper venous system.

Antineoplastic Combined Chemotherapy Protocols↗

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Cadaver↗