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Biomedical subjects

R D Barr

Publications and source records attributed to R D Barr.

At least 19 recordsLinked to original sources
PubMed1995

Mineral homeostasis and bone mass at diagnosis in children with acute lymphoblastic leukemia.

OBJECTIVE: To determine whether the osteopenia and unusual fractures observed in children with acute lymphoblastic leukemia (ALL) were related to the disease rather than to its treatment. DESIGN: Prospective analysis of the bone and mineral status in 40 consecutive children with ALL seen in a pediatric tertiary-care referral center. METHODS: Biochemical indicators of mineral, endocrine, and vitamin D status were measured before initiation of therapy. Bone mass was determined radiographically and by dual-photon absorptiometry of the lumbar region of the spine (L2-L4). Correlations between clinical observations, leukemia variables, bone mass, and biochemical assessment were determined. RESULTS: At the time of diagnosis musculoskeletal pain was present in 36% of patients and was more common in children with CD10-positive leukemia and leukocyte counts less than 20 x 10(9) cells/L. Radiographic evidence of osteopenia and fractures was observed in 13% and 10% of children, respectively. The mean bone mineral content was normal. Bone mass measurement z scores correlated with plasma 1,25-dihydroxyvitamin D3 concentrations (r = 0.43, p < 0.05). Plasma calcium, magnesium, phosphorus, and 25-hydroxyvitamin D3 levels were normal. Low plasma osteocalcin (mean +/- SD, 1.6 +/- 1.6 nmol/L) and 1,25-dihydroxyvitamin D3 (33.4 +/- 26.4 pmol/L) values were observed. Parathyroid hormone levels were low in 14% of children. Hypercalciuria was detected in 64% of children. Urinary deoxypyridinoline was lower (p < 0.01) than in age-matched control subjects. Histomorphometric measurements of iliac bone showed abnormalities in mineralization in the biopsy specimens from three of nine children. CONCLUSION: Most children with ALL have alterations in bone metabolism and bone mass when first examined. These data suggest defective mineralization as the mechanism for decreased bone mass and implicate the leukemic process as causative.

Adolescent↗
PubMed1995

Xanthoma disseminatum in an infant with skeletal and marrow involvement.

PURPOSE: Xanthoma disseminatum is a rare non-Langerhans' histiocytosis of older children and adults with characteristic lesions involving the skin, mucous membrane and occasionally internal organs. We describe a case, presenting in infancy, with unique clinical features. PATIENT AND METHODS: The patient presented at 8 months of age with skin lesions subsequently found to have histologic, immunophenotypic, and ultrastructural characteristics of non-Langerhans' histiocytosis. In addition to extensive skin lesions, the patient also has involvement of the buccal mucosa, lips, eyelids, bones, bone marrow, and possibly liver and spleen. RESULTS: Clinical and pathological features of the patient are suggestive of xanthoma disseminatum. Treatment with cytotoxic, immunomodulatory, and lipid-lowering agents has been unsuccessful to date. CONCLUSION: Unique characteristics of this case of xanthoma disseminatum include the patient's young age, lytic bone lesions, and previously undescribed bone marrow involvement.

Bone Marrow↗
PubMed1994

The challenge of childhood cancer in the developing world.

Causes of morbidity and mortality, in children in the developing world, are changing. Cancer is assuming increasing importance. The incidence in such countries is probably substantially underestimated, particularly in relation to brain tumours. However, real differences, from circumstances in industrialized societies, do exist; as in the relative prevalences of leukaemias and lymphomas. Furthermore, some forms of cancer, e.g. Hodgkin's disease and Wilms' tumour, seem to behave more aggressively in children in developing countries. Challenges to be addressed in these areas include inadequate knowledge, resource deficiencies and co-morbidity (especially malnutrition and infection). Solutions lie in approaches to health information and health care delivery systems, health professional education and essential national health research. To these ends, long-term collaboration should be established with colleagues, partner institutions and relevant organizations from more privileged parts of the world.

Child↗
PubMed1994

Effect of disease and chemotherapy on hemostasis in children with acute lymphoid leukemia.

PURPOSE: We sought to determine the effect of disease and combination chemotherapy on the hemostatic system in children with acute lymphoid leukemia (ALL). PATIENTS AND METHODS: We conducted a prospective study of children newly diagnosed with ALL. Plasma samples were obtained at four time points: at diagnosis before therapy, 5 days after administration of L-asparaginase alone, after the remission induction program, and at completion of the consolidation phase. Plasma levels of 21 hemostatic proteins were measured. The amount of thrombin generated following activation with an APTT reagent was quantitated. RESULTS: At diagnosis there were significant elevations in factors VIII, IX, von Willebrand, alpha 2-macroglobulin and protein S. In contrast, there were significant reductions in protein C, prekallikrein, and factors XIIIA and XIIIS. L-asparaginase treatment alone decreased concentrations of 11 proteins, with antithrombin III being affected to the greatest extent. After multiagent chemotherapy, not including L-asparaginase, concentrations of most proteins increased to or above baseline. At completion of consolidation therapy, which included weekly L-asparaginase administration, concentrations of most proteins were decreased compared with baseline values. The amount of thrombin generated following activation with an APTT reagent was similar to adults. CONCLUSION: Plasma concentrations of coagulation proteins are affected by disease (ALL) alone and by combination chemotherapy with or without L-asparaginase. There is no impairment of in vitro capacity to generate thrombin. L-asparaginase alone caused a decrease in almost all proteins; however, ATIII was affected to the greatest extent.

Adolescent↗
PubMed1992

Management of children with acute lymphoblastic leukemia by the Dana-Farber Cancer Institute protocols. An update of the Ontario experience.

The primary purpose of this study was to determine the therapeutic efficacy of a protocol of treatment for acute lymphoblastic leukemia (ALL) in children. A prospective approach was adopted with an inception cohort of patients. Outcome measures were assessed on December 31, 1990. The study was conducted at two tertiary care centres (pediatric oncology programs) in Ontario, Canada. All children with ALL were eligible for study and consecutive recruitment took place between May 1984 and July 1987. They were classified at diagnosis into one of three categories for risk of relapse according to standardized criteria. Thirty-nine children were designated as having standard risk (SR), 31 as having high risk (HR), and 12 as having very high risk (VHR) disease. All patients are included in the analysis. Treatment was administered according to risk category-specific chemotherapy protocols, the details of which have been published. A distinguishing feature of these strategies is the intensive use of intramuscular L-asparaginase. Patients remained on these regimens for 2 years or until relapse or toxic death (events) ensued. Total and event-free survival data were determined by life-table analysis (Kaplan-Meier plots). With a minimum interval from diagnosis of 186 weeks and a median interval exceeding 5 years, the cumulative proportion of the entire cohort (C) surviving is 85% [95% confidence interval (CI), 77-93%]. For the respective risk groups, the corresponding proportions are SR 94% (95% CI, 87-100%), HR 74% (95% CI, 59-89%), and VHR 81% (95% CI, 59-100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Disseminated Langerhans cell histiocytosis in identical twins unresponsive to recombinant human alpha-interferon and total body irradiation.

Monozygotic twin boys presented at 1 year of age with seborrheic skin rash, otorrhea, and hepatosplenomegaly. Skin biopsy confirmed Langerhans cell histiocytosis. Treatment with conventional antineoplastic drugs and with calf thymus extract was ineffective. The disease remained refractory to recombinant human alpha-interferon and to low-dose total body irradiation, and the children died between 3 and 3 1/2 years of age.

Combined Modality Therapy↗
PubMed1992

A comprehensive multiattribute system for classifying the health status of survivors of childhood cancer.

PURPOSE: A multiattribute health status classification system was devised to describe comprehensively the health status of survivors of childhood cancer. METHODS: The system consists of seven attributes: sensation, mobility, emotion, cognition, self-care, pain, and fertility. Three to five levels of functioning are defined for each attribute. Any specific combination of seven attribute levels constitutes a health state. In the first survey, the system was used to classify the health status of 20 children currently undergoing therapy for high-risk acute lymphoblastic leukemia (ALL), Wilms' tumor, or neuroblastoma, and eight who had completed treatment. A second survey consisted of 13 children with brain tumors on active treatment. RESULTS: In general, independent ratings by clinicians were in agreement, and consensus was readily achieved in 1 to 2 minutes per patient. Children on therapy experienced a higher burden of morbidity than those off treatment. Brain tumor patients experienced more morbidity than patients in the first survey. CONCLUSION: The multiattribute system provides a compact but comprehensive tool for long-term follow-up of survivors of childhood cancer. It captures both multiple sequelae and varying levels of severity. By using a mathematical utility function, a single summary score of health-related quality of life may be assigned to each health state. Additional studies to establish reproducibility, validity, responsiveness, and generalizability are indicated.

Activities of Daily Living↗
PubMed1991

The short-term reproductive toxicity of cyclophosphamide in the female rat.

Cyclophosphamide (CTX) is a potent ovarian toxicant. Previous studies of the acute effects of CTX in the rat have demonstrated widespread ovarian follicle atresia, reduced serum estradiol, and progesterone with normal serum LH and FSH. The present investigations demonstrate that a single injection of CTX induces ovarian toxicity that reflects the loss of growing ovarian follicles. CTX induces a sensitization of serum FSH in response to GnRH within 24 h; this sensitization is lost by 7 days, and after 14 days the animals are capable of normal mating behavior. The observed protection of primordial follicles from the acute administration of CTX under these experimental circumstances may be related to the stage of the granulosa cell cycle of these follicles.

Animals↗
PubMed1991

The agonist (d-leu-6,des-gly-10)-LHRH-ethylamide does not protect the fecundity of rats exposed to high dose unilateral ovarian irradiation.

Attempts to protect the ovary from the toxic effects of radiation and chemotherapy are relevant to the management of the young patient with cancer. Previous studies in a variety of animal species with several types of agonists of GnRH have shown promise in affording gonadal protection using indirect indices of reproductive function. The current investigations are based on these observations. Female rats were treated with (d-leu-6,des-gly-10) LHRH-ethylamide (GnRHa) from day 22 to day 37 of life. Sham-irradiation or unilateral irradiation of the left ovary was performed on day 30. The animals were mated following resumption of cycles and sacrificed on day 21 of pregnancy. There was no significant effect of ovarian artery ligation. Radiation reduced ovarian function ipsilateral to the radiation. GnRHa alone did not affect reproductive performance significantly. GnRHa and radiation combined resulted in no reproductive protection but augmented the damage done to the ipsilateral ovarian weight and to numbers of corpora lutea and fetuses. Under these experimental circumstances the agonist provided no protection.

Animals↗
PubMed1991

Right atrial catheters in children with cancer: a decade of experience in the use of tunnelled, exteriorized devices at a single institution.

In the period 1980-1988, data were collected (prospectively from 1985) on the clinical utilization of exteriorized, tunnelled, right atrial catheters in children with cancer undergoing treatment at a single institution. A total of 231 devices were placed in 180 patients. Individual catheters were in place for a median of 314 days, with a total experience of more than 83,000 days. This form of long-term venous access was used for the administration of antineoplastic agents and other drugs, blood products (especially platelet concentrates and packed red blood cells), parenteral nutrition and infusion of other fluids, obtaining samples of venous blood, and giving intravenous contrast media and radiolabeled substances for radiological investigations. Almost 80% of catheters were removed electively (on completion of scheduled therapy or at death), with the remainder requiring removal in the management of infection or device displacement. Infections were manifest in two-thirds of the children, most commonly (60%) at the catheter exit site on the anterior chest wall. "Clinically significant" infection occurred with a frequency of 2.1 episodes per 1,000 patient days, with Staphylococcal species predominating except for the circumstances of catheter colonization in which Gram-negative, waterborne organisms were most in evidence. Empirical, intravenous, combined antibiotic therapy was effective in approximately 90% of "clinically significant" episodes. Mechanical complications (traveling, leakage, or catheter occlusion) occurred less frequently and were managed by repairing or replacing the device, or clearing the block. Indwelling catheters, of the Broviac or Hickman types, offer major advantages with acceptable morbidity in the management of children with malignant diseases.

Adolescent↗
PubMed1990

Recurrent acute splenic sequestration crisis due to interacting genetic defects: hemoglobin SC disease and hereditary spherocytosis.

A 14-year-old boy with hemoglobin SC disease and alpha-thalassemia-2 experienced five episodes of acute splenic sequestration crisis (ASSC), while two of his siblings with identical globin genotypes (SC and -alpha/alpha alpha) had no such experience. To determine if an additional red blood cell (RBC) defect was responsible for the unusual occurrence of frequent ASSCs, we performed detailed rheologic characterization and membrane protein analysis on RBCs from the proband and other members of his family. Reduced surface area, increased mechanical instability, and decreased spectrin content of the membrane, distinguishing features of RBCs in hereditary spherocytosis, were observed in cells from the proband and his mother, but not in cells from other family members. These findings are consistent with the dominant inheritance of spherocytosis by the proband. We suggest that the combined effects of SC disease and spherocytosis in the proband resulted in decreased RBC deformability and led to increased splenic trapping, intrasplenic sickling, and consequently, recurrent sequestration crisis. Marked clinical and hematologic improvement occurred from splenectomy. Thus, inheritance of interacting genetic defects, sickling hemoglobinopathy, and hereditary spherocytosis appear to be responsible for the unusual clinical manifestation of recurrent ASSC in this patient.

Anemia, Sickle Cell↗