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Biomedical subjects

V Blanchette

Publications and source records attributed to V Blanchette.

At least 55 records · Page 3Linked to original sources
PubMed1994

Concurrent RhGM-CSF does not offset myelosuppression from intensive chemotherapy: randomized placebo-controlled study in childhood acute lymphoblastic leukemia.

To determine whether recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) can offset the myelosuppressive effects of intensive chemotherapy, we carried out a double-blind placebo-controlled trial in which 40 patients with acute lymphoblastic leukemia (ALL) were randomized into two groups of 20 each. One group received rhGM-CSF (5.5 micrograms/kg SC) coadministered with chemotherapy and the other, placebo coadministered with chemotherapy from day 5 to day 11 and from day 19 to day 25 of the 28-day intensification phase of our institutional high-risk protocol for childhood ALL. The results indicate that, at the dose and schedule used, rhGM-CSF did not prevent neutropenia or shorten the number of days required to complete this phase of therapy. In addition, the treated and placebo groups showed no significant difference in absolute neutrophil counts, number of days with neutropenia, number of days with fever, number of days spent in hospital, or number of days on antibiotics during the 28-day study period. There was also no difference between the two groups in the number, type, or severity of infectious episodes. Two of 20 patients in the treatment group have relapsed, whereas none of the patients in the placebo group has yet relapsed (follow-up: 3-37 months), but these events were not statistically significant. We conclude that treatment with rhGM-CSF at the dose and schedule employed is not clinically beneficial.

Adolescent↗
PubMed1994

Heparin therapy in pediatric patients: a prospective cohort study.

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Idiopathic thrombocytopenia and neutropenia in childhood.

PURPOSE: Between 1975 and 1990, 13 patients seen at The Hospital for Sick Children, Toronto, Ontario, were noted to have concurrent idiopathic thrombocytopenia and neutropenia (ITN; platelet count < 150 x 10(9)/L; absolute neutrophil count < 1.5 x 10(9)/L). These patients all had normal marrow function and no evidence of systemic disease. PATIENTS AND METHODS: A detailed chart review was performed to define the clinical and laboratory features of these patients. RESULTS: Although this was a heterogeneous group of patients, they shared several common characteristics. The disease followed a chronic course with thrombocytopenia or neutropenia or both that persisted or recurred over the entire period of follow-up in all patients (18 months to 15 years). The disease was associated with splenomegaly in eight patients and lymphadenopathy in nine patients. Boys were affected more frequently than were girls (ratio 11:2). Thrombocytopenia improved temporarily during treatment with corticosteroids, i.v. immunoglobulin G, RhoGAM, and a variety of immunosuppressive agents; however, neutropenia tended to be much more resistant to these therapies. Splenectomy was ineffective in two children in whom the procedure was performed. Platelet of and neutrophil antibodies or both were detected in five of six patients who were tested, suggesting an autoimmune cause for the cytopenias. CONCLUSIONS: These findings suggest that ITN in childhood is distinct from immune thrombocytopenic purpura, particularly in terms of its chronicity and poor response to therapy.

Adolescent↗
PubMed1993

Neonatal alloimmune thrombocytopenia due to a new platelet-specific alloantibody.

An infant with severe neonatal alloimmune thrombocytopenia is described in whom an antibody directed at a new platelet-specific alloantigen, Ca (HPA-6b), is implicated. The new alloantigen is of low frequency in the population and was localized to platelet glycoprotein (GP) IIIa. Immunoprecipitation studies using murine monoclonal antibodies specific for the GP complex IIb-IIIa and GPIIIa alone (AP2 and AP3) suggest that the location of the Ca epitope on GPIIIa may be near the binding site for AP3. Neonatal alloimmune thrombocytopenia associated with Ca is likely to be as severe as that seen in cases due to incompatibilities for the HPA-1 (PIA) and HPA-4 (Pen) platelet alloantigen systems, because each is located on GPIIIa, a densely represented molecule on the platelet surface.

Antigens, Human Platelet↗
PubMed1993

Downregulation of the anti-HLA alloimmune response by variable region-reactive (anti-idiotypic) antibodies in leukemic patients transfused with platelet concentrates.

Approximately 30% to 40% of patients with acute leukemia receiving repeated pooled random-donor platelet transfusions develop anti-HLA alloantibodies. Over time, however, serum anti-HLA concentrations decrease in approximately 50% of these patients, despite continued exposure to platelet and/or red blood cell transfusions. Using an enzyme-linked immunosorbent assay to measure serum Igs, the present study demonstrates that the sera of 67% of 82 transfused patients exhibiting a decrease in anti-HLA contain antibodies (anti-idiotypes) that react with the variable (V) region of anti-HLA antibodies. Anti-HLA binding to platelet membranes could be inhibited by these serum antibodies in 36% of the patients, indicating they had paratope-related reactivity. Protein G sepharose absorption showed that the anti-HLA V region-reactive antibodies were IgG. Of the 43 patients who had a decrease in anti-HLA levels, that were 16 whose anti-HLA decreased to undetectable levels; 7 (44%) developed anti-idiotypic antibodies that could specifically inhibit their own previously anti-HLA-positive serum. In contrast, antibodies with reactivity to the V region of anti-HLA antibodies (anti-idiotypes) were not demonstrable in patients who developed anti-HLA that did not decrease or disappear. The findings suggest that the development of anti-HLA V region-reactive antibodies (anti-idiotypic antibodies) correlates with a decrease in anti-HLA antibody formation in patients multiply transfused with platelet concentrates. The observations indicate that anti-idiotypic antibodies may downregulate alloimmune responses in patients undergoing repeated allostimulation during platelet transfusion therapy.

Acute Disease↗
PubMed1993

National survey of neonatal transfusion practices: II. Blood component therapy.

Neonatal transfusion practices during 1989 of 452 institutions involved in transfusing infants were surveyed by questionnaire. Most respondents (77%) transfused fresh frozen plasma appropriately (ie, primarily to treat coagulation disorders). However, 11% stated that their most frequent use of fresh frozen plasma was solely to treat hypovolemia, a practice generally not recommended. Seventy-eight percent of respondents transfused platelets to treat bleeding infants with blood platelet counts of less than 50 x 10(9)/L; 84% gave platelets to sick, premature neonates with counts of less than 50 x 10(9)/L whether or not bleeding was evident. Only 35% of respondents transfused granulocytes for neonatal sepsis; most institutions used buffy coats isolated from units of blood--a product readily available, but of questionable efficacy when compared with leukapheresis granulocytes. Ninety-three percent of respondents provided blood components with low risk of transmitting cytomegalovirus: components from seronegative donors were used by 84%, leukocyte-reduced products by 6%, and a combination by 10%. Thirteen percent of respondents gave gamma-irradiated blood components to all and 46% gave them to some neonates to prevent graft vs host disease. Forty-one percent did not routinely irradiate. Ten percent of respondents used leukocyte reduction instead of gamma irradiation to prevent graft vs host disease, a practice currently not advocated. Thus, national transfusion practices for neonates are variable, controversial, and, occasionally, other than those usually recommended. Additional research and educational efforts are needed to ensure optimal transfusion therapy.

Blood↗
PubMed1993

National survey of neonatal transfusion practices: I. Red blood cell therapy.

Neonatal blood component transfusion practices during 1989 were surveyed via a questionnaire developed by the Pediatric Hemotherapy Committee of the American Association of Blood Banks. Of 1790 questionnaires mailed, 452 were selected to form the database for this analysis because they were from institutions in which neonates were transfused. Nearly all institutions contained intensive care units directed by neonatologists and were involved in the management of high-risk infants. Results from institutions serving as the primary pediatric teaching hospital of a medical school were compared with those with no medical school affiliation. Thirty-six percent of primary pediatric teaching hospitals and 52% of hospitals with no medical school affiliation performed pretransfusion testing in excess of that required, resulting in additional blood loss in neonates. Sixty-six percent of primary pediatric teaching hospitals used fresh frozen plasma to adjust the hematocrit of red blood cell concentrates prior to transfusion (a practice increasing donor exposure), compared with only 29% of hospitals with no medical school affiliation. The usual indication for small-volume red blood cell transfusions in severely ill neonates was to maintain a desired hematocrit level, whereas for stable infants, red blood cell transfusions were given to treat symptomatic anemia, rather than to maintain a predetermined hematocrit. As found in 1985, neonatal transfusion practices in 1989 were variable. However, improvements have occurred since 1985 to suggest that further research and educational efforts may serve to promote even better neonatal transfusion therapy.

Blood Component Transfusion↗
PubMed1992

Pain perception and effectiveness of the eutectic mixture of local anesthetics in children undergoing venipuncture.

The emulsion of lidocaine and prilocaine (EMLA) is effective in preventing the pain of venipuncture in children. It is therefore important to identify children who could benefit the most from EMLA. We studied the safety and feasibility of two methods of application of EMLA (patch and cream) in a randomized, open-label trial of EMLA patch versus EMLA cream in 160 children with chronic diseases undergoing venipuncture. EMLA patch or cream was applied 60 to 120 min before puncture. Pain was assessed by the children using a visual analogue score. Children also scored the pain of their last puncture and the pain of removing the tape. EMLA patch and cream had similar efficacy (visual analogue scores for the venipuncture were 8.5 +/- 16 and 9.5 +/- 17 out of 100, respectively). Side effects occurred in similar frequencies in the two groups. Adhesiveness of the patch was less effective than that of the cream with Tegaderm. Age was a major determinant of pain perception; younger children recalled more severe pain in their previous puncture. Children recently diagnosed had higher visual analogue scores than those with a long history of chronic disease. We concluded that EMLA patch and cream have a similar efficacy in children undergoing venipuncture. Young children recently diagnosed with chronic disease are most likely to benefit from EMLA.

Adolescent↗
PubMed1991

Different forms of chronic childhood thrombocytopenic purpura defined by antiplatelet autoantibodies.

To determine whether detection of antiplatelet autoantibodies (AAb) to glycoproteins IIb/IIIa and Ib/IX may be useful in defining different forms of chronic thrombocytopenic purpura (TP) in children, we analyzed for AAb the platelet and plasma samples from 36 children with chronic TP (mean duration 4.4 years), from 31 children with normal platelet counts at the time of blood sampling but with chronic TP in the past (mean duration 2.9 years), and from 23 adults with chronic TP; the results were correlated with the clinical data. Antiplatelet autoantibodies were detected in 26 (72.2%) of 36 children with ongoing TP, 15 (48.4%) of 31 children with TP in the past, and 12 (66.7%) of 18 adults with TP. All children with high AAb ratios (greater than 5 times the control mean + 3 SD) were more than 8 years of age at diagnosis (mean age 12.4 years compared with 7.1 years in children with moderate or negative AAb levels; p = 0.003). The results suggest that the outcome for adolescents with high platelet-associated AAb levels may be similar to that of adults, whereas younger children may have a greater chance of spontaneous remission. The children with chronic TP in the past and elevated platelet-associated AAb levels may have a "compensated" TP and therefore may be at risk for relapses. Future studies aimed at serial AAb determination throughout the patients' courses may further define TP subgroups.

Adolescent↗
PubMed1991

White cell depletion of red cell and pooled random-donor platelet concentrates by filtration and residual lymphocyte subset analysis.

This study comparing the relative white cell (WBC)-depleting efficiency of single and double filtration used two filters and new, sensitive, and reliable methods for performing WBC counts on WBC-depleted blood products. A single filtration of red cell (RBC) concentrates with a cotton-wool filter reduced WBC content by 98.64 percent, but the range of residual WBCs was wide, and many filtered units still contained more than the theoretical immunizing dose of 5 to 10 x 10(6) WBCs. A second filtration, however, always produced RBC units that had less than 5 x 10(6) WBCs. Although the degree of WBC depletion observed after a single filtration of a 6-unit pool of random-donor platelet concentrates was greater with a polyester filter than with the cotton-wool filter (98.92 vs. 98.14% reduction, respectively, when mean prefiltration WBC count was less than 600 x 10(6], in both cases, 25 percent of filtered products still contained greater than 5 x 10(6) WBCs; a second filtration (with the cotton-wool filter), however, produced units that were always below the immunizing dose. All double-filtered platelet concentrates had less than 10(6), and one-half had less than 10(4) residual WBCs. Platelet loss was similar with both filters (+/- 16% loss with one filtration). The effectiveness of the filters in producing products that were WBC-depleted below the immunizing dose was dependent on the prefiltration WBC content (but not on the age of the units), and it may be worthwhile to employ methods to ensure that total prefiltration WBC count of the product is less than 400 x 10(6).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1990

Hodgkin's disease in children: treatment with MOPP and low-dose, extended field irradiation without laparotomy. Late results and toxicity.

The 10 year results of a trial of bimodal treatment of Hodgkin's disease in children with 6 cycles of MOPP and low-dose extended field irradiation, without staging laparotomy, were for 57 children in all stages as follows: survival 85%, relapse-free survival 80%, and survival-free of second relapse 86%. There were three fatal toxic events, two due to viral infection and one to a second malignant tumor (NHL). Three other patients developed a second malignant tumour, and one developed a thyroid adenoma. No patient developed acute leukemia. These results are compared with the results of treatment of surgically staged children by extended field irradiation alone, with bimodal treatment reserved for relapse or advanced disease at diagnosis. Initial bimodal treatment improved the overall 10 year survival free from a second relapse rate by 20% (86% vs. 66%). No major difference in treatment toxicity between these two groups has emerged during the first 10 years of follow-up. We conclude that, except for favourable CS-1 presentations, children with Hodgkin's disease confined to the lymphatic system should be given bimodal treatment, but that the least morbid effective combination remains to be determined.

Adolescent↗
PubMed1989

Neonatal autoimmune thrombocytopenia: role of high-dose intravenous immunoglobulin G therapy.

High-dose intravenous immunoglobulin G (IVIgG) therapy results in a rapid reversal of thrombocytopenia in over 80% of children with acute immune thrombocytopenic purpura (ITP). Comparable results were observed in eleven infants with an analogous condition, neonatal autoimmune thrombocytopenia (NATP), who received IVIgG (2 g/kg body weight) administered alone (n = 6) or in combination with steroids (n = 5). The median platelet count pre-IVIgG therapy was 25 X 10(9)/l (range 5 to 74 X 10(9)/l). The overall response rate to IVIgG therapy, administered alone or in combination with steroids was 75% (12 of 16 treatment episodes). A good response to therapy was defined as an increase in the platelet count to greater than or equal to 50 X 10(9)/l and at least twice the pre-treatment value at 48 h after completion of the IVIgG infusion. The rapid and generally excellent response to IVIgG therapy in infants with NATP suggests that this treatment approach should be considered as first-line therapy for severely thrombocytopenic infants with this self-limiting but potentially serious disorder.

Autoimmune Diseases↗
PubMed1988

Random donor platelet crossmatching: comparison of four platelet antibody detection methods.

The standard lymphocytotoxicity assay (LCT), a biotin-avidin enzyme immunoassay (ELISA), platelet suspension immunofluorescence test (PSIFT), and platelet radioactive antiglobulin test (PRAT) were examined in prospective crossmatching for selection of compatible random donor platelets for refractory patients. One hundred seven episodes of pooled random donor platelet transfusions were evaluated in 26 patients. There was good reproducibility of results by individual techniques. Concordance of results by the different methods was 40-60%. One-hour and 24 hr posttransfusion corrected count increments (CCI) were compared as parameters for assessing success or failure of the transfusion. Using a rank scoring system, the relative efficiency of predictiveness for all transfusions was PRAT greater than LCT greater than PSIFT greater than ELISA. Combination of PRAT and LCT afforded the best predictability and sensitivity was higher than for either PRAT or LCT alone (93 vs. 79 and 62%, respectively). Mean posttransfusion CCI (x 10(9)/L) following PRAT-compatible platelets was 13.9 +/- 12.7 at 1 hr and 7.3 +/- 6.9 at 24 hr; following PRAT-incompatible platelets, 5.7 +/- 7.8 (1 hr) and 2.1 +/- 4.1 (24 hr). Results were similar for LCT-tested platelets. A radioimmunofiltration modification of the PRAT developed and used in selected cases was simple, fast, efficient, and inexpensive. The study indicated that the techniques evaluated are practical and feasible for routine use in the provision of compatible random donor platelets to the refractory patient who has no other cause for increased platelet destruction.

Adolescent↗
PubMed1988

A complete deletion of the factor IX gene and new TaqI variant in a hemophilia B kindred.

We report a hemophilia B kindred in which the proband has a complete deletion of the factor IX gene extending a minimum of 80 kilobase pairs (kb) 3' of the gene. This individual has severe factor IX deficiency with no detectable circulating factor IX protein. In common with one previous report, despite a total deletion of the factor IX gene, this patient has not developed antibodies to factor IX. The mother of the proband was found to have a new TaqI variant of the factor IX gene on the nondeletion-bearing X chromosome. The location of the altered TaqI site was found to be 5' of exon IV between residues 9731-9734 and does not affect the function of the factor IX protein. The familial natures of both the variant allele and the deletion were established. In addition a study of this kindred at the DXS99 locus demonstrated the first reported recombination event between this site and the factor IX gene.

Blood Coagulation Tests↗