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Biomedical subjects

R I Parker

Publications and source records attributed to R I Parker.

At least 19 recordsLinked to original sources
PubMed2001

Randomized, double-blind, crossover, placebo-controlled trial of intravenous ondansetron for the prevention of intrathecal chemotherapy-induced vomiting in children.

BACKGROUND: The purpose of this study was to determine the effectiveness of intravenous ondansetron in preventing vomiting after the administration of intrathecal chemotherapy in children. PATIENTS AND METHODS: Twenty-six children (ages 18 mo to 15 y) receiving intrathecal chemotherapy with either methotrexate or the combination of methotrexate, hydrocortisone, and Ara-C for the prophylactic treatment of central nervous system leukemia were randomly assigned to receive an infusion of normal saline or ondansetron at one of two doses (0.15 or 0.45 mg/kg) 30 minutes before undergoing the procedure. One hundred forty-six infusions were administered (51 placebo, 47 at the lower ondansetron dose, and 48 at the higher dose). Each patient acted as his or her own control, and each patient was studied at least three times. RESULTS: Twenty-three of 26 patients (88.5%) had postprocedural vomiting on at least one occasion. At least one episode of vomiting occurred during the 24 hours after the procedure in fifty-two of the procedures (35.6%). The incidence of vomiting was significantly greater after infusion of placebo than after either low-dose or high-dose ondansetron. The likelihood of severe vomiting was even more significantly reduced by the preadministration of ondansetron. Almost all of the intrathecal treatments associated with severe vomiting occurred after the infusion of placebo. CONCLUSIONS: Vomiting induced by intrathecal chemotherapy can be greatly reduced by the intravenous administration of ondansetron before the procedure, and severe vomiting can be virtually eliminated.

Adolescent↗
PubMed2000

Hematologic aspects of systemic mastocytosis.

Systemic mast cell disease is characterized by bone marrow involvement by mast cells and frequently by peripheral blood cytopenias. The coexistence of hematologic disorders, such as myeloproliferative or myelodysplastic syndromes, or of lymphoreticular malignancies with SMCD is common. Overt mast cell leukemia is rare. In general, patients who coexhibit a severe hematologic disorder tend to have a more compressed clinical course and a worse prognosis. Hemorrhage can be a result of heparin release from stimulated mast cells.

Adolescent↗
PubMed1998

RAS mutations in pediatric leukemias with MLL gene rearrangements.

Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, 1 was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.

Adolescent↗
PubMed1997

Energy-dependent expression of platelet-von Willebrand factor on the surface of unstimulated and stimulated platelets.

We have studied the energy requirements (adenosine triphosphate) for the expression of platelet-von Willbrand factor on platelets under conditions in which glycolysis and/or oxidative phosphorylation were inhibited. We found that platelet-vWf expression on the surfaces of both unstimulated and stimulated platelets required energy and was maximally decreased when metabolic ATP was maximally depleted. Platelet-vWf expression correlated directly with estimates of adenylate energy charge in both unstimulated and stimulated platelets. In addition, platelet shape change and agonist-induced intracellular Ca2+ flux were maintained at lower AECs than were either platelet aggregation or alpha-granule secretion. Our results indicate that the surface expression of platelet-vWf on unstimulated platelets is a dynamic process, and that energy is required to maintain basal amounts of platelet-vWf on the platelet surface. Our data also suggest that the metabolic ATP required to effect changes in platelet shape is less than that necessary to maintain basal platelet-vWf surface expression or to produce full alpha-granule secretion. We show that platelet-shape change in the absence of alpha-granule secretion can result in an increase in platelet-vWf surface expression.

2,4-Dinitrophenol↗
PubMed1997

Etiology and treatment of acquired coagulopathies in the critically ill adult and child.

Excessive bleeding frequently complicates the care of critically ill patients. Except in the case of trauma or inpatients with known coagulopathies, the bleeding is generally not directly related to the illness that results in admission to the intensive care unit. In general, the causes of the bleeding can be divided into three categories: consumptive coagulopathies, bleeding related to "hepatic issues," and iatrogenic causes. In most circumstances, the pathogenesis and management of these acquired coagulopathies do not differ between the adult and child patient. However, some differences do exist in regards to the clinical manifestations and management of some consumptive coagulopathies. This article reviews the more common causes of bleeding in the critically ill patient and outlines diagnostic and treatment approaches for these patients. Particular emphasis will be placed on the differences in presentation and management where differences exist.

Adult↗
PubMed1997

Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children.

OBJECTIVE: We have used the combination of midazolam, a short-acting benzodiazepine, and ketamine, a "dissociative anesthetic," to provide conscious sedation for invasive or lengthy procedures. METHODS: A total of 350 procedures (74 lumbar punctures, 97 bone marrow aspirations or biopsies, 84 radiotherapy sessions, and 95 imaging studies) were performed on 68 children, 4 months to 17 years of age, in both inpatient and ambulatory settings. All patients had an intravenous line in place and were monitored for heart rate and O2 saturation by pulse oximetry for the duration of the procedure and recovery time. Blood pressure was monitored periodically (every 5 to 30 minutes). Oxygen and suction equipment was available during the procedure. In addition to the individual performing the procedure, a second staff member trained in airway management (eg, physician, nurse practitioner, or registered nurse) was present to monitor vital signs and respiratory status. Patients were sedated initially with midazolam (0.05 to 0.1 mg/kg intravenously; maximum single dose of 2 mg, maximum total dose of 4 mg), followed by ketamine (1 to 2 mg/kg intravenously). During lengthy procedures, additional doses of ketamine (0.5 to 1 mg/kg) were given as necessary. Effectiveness of the sedation, recovery time, and adverse events associated with the sedative regimen were documented. RESULTS: All patients were effectively sedated with this regimen. Four patients experienced transient decrease in O2 saturation (<85%) requiring temporary interruption of the procedure and oxygen by blow-by; the procedure was subsequently completed without incident in each case. Two patients experienced significant agitation during recovery from sedation. This side effect resolved spontaneously after 5 to 10 minutes in one patient and was effectively treated with diphenhydramine hydrochloride in the other. Twenty-four lumbar punctures were associated with transient decrease in O2 saturation (88% to 92%), which improved by relief of neck flexion and/or blow-by oxygen. No hypotension, bradycardia, or respiratory depression requiring respiratory support or reversal of sedation was noted. Anesthesia recovery time ranged from <15 minutes to 120 minutes with >70% of patients recovering within 30 minutes. Most patients demonstrated an increase in oral secretions requiring occasional suctioning. Transient sleep disturbances were reported in only two patients. CONCLUSIONS: This sedative regimen of intravenous midazolam and ketamine was found to be safe and effective. Its use has greatly reduced patient and parent anxiety for diagnostic and therapeutic procedures.

Adolescent↗
PubMed1993

Failure to mobilize intracellular calcium in response to thrombin in a patient with familial thrombocytopathy characterized by macrothrombocytopenia and abnormal platelet membrane complexes.

We report a mother and son who were found to have macrothrombocytopenia, prolonged bleeding time, and abnormal platelet responses to thrombin. Transmission electron microscopy performed on the son's platelets demonstrated an unusual arrangement of membrane complexes formed by association of the open canalicular and dense tubular systems. Number and appearance of platelet alpha-granules, dense bodies, and mitochondria were normal. These platelets demonstrated normal agonist-induced Ca2+ flux in response to collagen and supranormal responses to arachidonic acid but displayed no increase in intracellular free Ca2+ in response to thrombin. Platelet surface glycoproteins IIb-IIIa, Ib, and granular membrane protein-140 measured by fluorescence-activated flow cytometry, along with platelet content of von Willebrand factor and fibrinogen, were normal. The von Willebrand factor binding function of GP-Ib on these platelets was also normal. We believe that this family demonstrates a unique macrothrombocytopenia syndrome characterized by deficient Ca2+ mobilization in response to thrombin that is not related to a defect in GP-Ib.

Adolescent↗
PubMed1993

Introducing total quality management in an area health board.

It is essential for the health care industry to demonstrate a quality service. The Canterbury Area Health Board (CAHB), New Zealand is in the process of establishing the principles of Total Quality Management (TQM) and this paper addresses the key issues of committing to TQM. Highlighted are the Board's implemented programmes, business plan and role of the health care industry.

Delivery of Health Care↗
PubMed1993

A human chimera for von Willebrand disease following bone marrow transplantation.

PURPOSE: von Willebrand disease (vWD) is a common bleeding disorder characterized by quantitative or qualitative defects in von Willebrand factor (vWF), a protein important for coagulation and platelet adhesion. There are two forms of vWF currently recognized: plasma vWF synthesized by endothelial cells and platelet vWF produced within megakaryocytes. Although both plasma and platelet vWF play important roles in overall hemostasis, the relative contribution of each form is not clear. PATIENTS AND METHODS: We report the results of bone marrow transplantation from a donor with Type I vWD into a hemostatically normal recipient. RESULTS: Following engraftment, the recipient appears to be a human chimera for vWD, with normal amounts of plasma vWF from endogenous endothelial cells, but low levels of platelet vWF derived from donor megakaryocytes. CONCLUSIONS: Although the vWD chimerism has not been associated with any clinical manifestations, the bleeding time has become prolonged, suggesting that platelet vWF is important for normalization of the bleeding time.

Adolescent↗
PubMed1992

Absence of the largest platelet-von Willebrand multimers in a patient with lactoferrin deficiency and a bleeding tendency.

We have studied a young male with lactoferrin deficiency and a bleeding tendency responsive to cryoprecipitate. This child has had increased bleeding following surgical procedures and a variably prolonged template bleeding time. The patient has a normal platelet count, normal in vitro platelet ATP secretion and aggregation in response to a variety of agonists, and normal concentration of plasma-von Willebrand factor ristocetin cofactor activity and antigen. Analysis of plasma-vWf multimers by agarose gel electrophoresis consistently demonstrated a subtle decrease in the largest vWf multimers. In contrast, analysis of the patient's platelet-vWf revealed normal vWf:Ag, decreased vWf ristocetin cofactor activity, and a striking absence of the high and intermediate size molecular weight vWf multimers. Analysis of surface bound platelet-vWf demonstrated normal amounts on the surface of unstimulated platelets, but after thrombin stimulation the platelet-vWf surface expression did not increase. This lack of increased platelet-vWf surface expression resulted from decreased binding of secreted platelet-vWf to be surface of stimulated platelets. These data suggest that the patient's bleeding tendency may be related to a defect in his platelet-vWf structure and/or mobilization. This case represents a unique demonstration of an abnormality of platelet-vWf in the presence of normal plasma-vWf, and supports the data indicating an important role for platelet-vWf in primary hemostasis.

Biopolymers↗
PubMed1992

Effect of platelet count on the DDAVP-induced shortening of the bleeding time in thrombocytopenic Gaucher's patients.

As part of an investigative protocol requiring serial liver biopsies in patients with Type I Gaucher's disease who were receiving enzyme replacement therapy, we gave 11 patients a total of 15 infusions of DDAVP (0.3 micrograms/kg IV) and measured the Simplate bleeding time pre- and postin-fusion. All patients were thrombocytopenic (one patient 100-150,000; seven 66-99,000; and three 50-65,000/microliters). Nine of 15 infusions resulted in at least a 2-min shortening of the bleeding time; in 6/11 infusions in which the platelet count was greater than 65,000, the bleeding time shortened to less than or equal to 10 min, in 1/11 it shortened greater than or equal to 2 min but not to less than or equal to 10 min. In only 2/4 infusions given to patients with platelet counts less than 65,000 did the bleeding time demonstrate any significant shortening. None of the six liver biopsies performed in the patients whose bleeding time shortened to less than or equal to 10 min resulted in any significant bleeding; blood products were not transfused either pre- or postprocedure. These limited data demonstrate that a high percentage of patients with platelet counts of 65-100,000/microliters can manifest a significant shortening of bleeding time following a standard infusion of DDAVP, and that in approximately half of these patients the bleeding time will shorten enough to safely allow the performance of a liver biopsy without the need for prophylactic transfusion of blood products.

Adolescent↗
PubMed1991

Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease.

BACKGROUND AND METHODS: Gaucher's disease, the most prevalent of the sphingolipid storage disorders, is caused by a deficiency of the enzyme glucocerebrosidase (glucosylceramidase). Enzyme replacement was proposed as a therapeutic strategy for this disorder in 1966. To assess the clinical effectiveness of this approach, we infused macrophage-targeted human placental glucocerebrosidase (60 IU per kilogram of body weight every 2 weeks for 9 to 12 months) into 12 patients with type 1 Gaucher's disease who had intact spleens. The frequency of infusions was increased to once a week in two patients (children) during part of the trial because they had clinically aggressive disease. RESULTS: The hemoglobin concentration increased in all 12 patients, and the platelet count in 7. Serum acid phosphatase activity decreased in 10 patients during the trial, and the plasma glucocerebroside level in 9. Splenic volume decreased in all patients after six months of treatment, and hepatic volume in five. Early signs of skeletal improvements were seen in three patients. The enzyme infusions were well tolerated, and no antibody to the exogenous enzyme developed. CONCLUSIONS: Intravenous administration of macrophage-targeted glucocerebrosidase produces objective clinical improvement in patients with type 1 Gaucher's disease. The hematologic and visceral responses to enzyme replacement develop more rapidly than the skeletal response.

Acid Phosphatase↗