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Biomedical subjects

R D Barr

Publications and source records attributed to R D Barr.

At least 55 records · Page 3Linked to original sources
PubMed1996

Boron levels in man: preliminary evidence of genetic regulation and some implications for human biology.

Boron is a ubiquitous constituent of man's external environment. Levels of the element in human blood reflect both acute and chronic exposure, usually as dietary intake (food and drinking water). There is an absolute requirement for boron in vascular plants but evidence for biological essentiality in animals (including man) is limited. A high body burden of the element may be harmful, especially to young animals (including human neonates). Information on boron deficiency is scanty. It has been proposed that boron contributes to living systems by acting indirectly as a proton donor and that it exerts a particular influence on cell membrane structure and function. The present study examines the variation in blood levels within and between human sibships and provides some support for the possibility that boron metabolism is subject to genetic regulation.

Adult↗
PubMed1996

Multiattribute utility function for a comprehensive health status classification system. Health Utilities Index Mark 2.

The Health Utilities Index Mark 2 (HUI:2) is a generic multiattribute, preference-based system for assessing health-related quality of life. Health Utilities Index Mark 2 consists of two components: a seven-attribute health status classification system and a scoring formula. The seven attributes are sensation, mobility, emotion, cognition, self-care, pain, and fertility. A random sample of general population parents were interviewed to determine cardinal preferences for the health states in the system. The health states were defined as lasting for a 60-year lifetime, starting at age 10. Values were measured using visual analogue scaling. Utilities were measured using a standard gamble technique. A scoring formula is provided, based on a multiplicative multiattribute utility function from the responses of 194 subjects. The utility scores are death-anchored (death = 0.0) and form an interval scale. Health Utilities Index Mark 2 and its utility scores can be useful to other researchers in a wide variety of settings who wish to document health status and assign preference scores.

Adolescent↗
PubMed1996

Hypermagnesiuria and hypercalciuria in childhood leukemia: an effect of amikacin therapy.

PURPOSE: The purpose of this study is to assess the effects of amikacin on renal proximal tubular function, and on magnesium (Mg) and calcium (Ca) status in children treated for acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Eighteen children (11 male/7 female, ages 2-18 years) receiving antileukemic therapy (Dana Farber Cancer Institute protocols 87-001 or 91-001) and admitted for febrile neutropenia to The Children's Hospital at Chedoke-McMaster, Hamilton, Ontario were recruited into this descriptive prospective study. Each child was treated with amikacin (7.5 mg/kg/12 h x 10-14 days) for one or more courses. RESULTS: No patient demonstrated elevations in amikacin trough levels. beta 2-Microglobulinuria, glucosuria, proteinuria, and hyperphosphaturia were absent. Children (50% presenting with hypomagnesemia (< 0.77 mmol/L) had a significant rise in mean urinary Mg:creatinine (0.46 +/- 0.27 versus 0.82 +/- 0.38 mmol, mean +/- SD, p < 0.05) in response to amikacin therapy and the mean Ca:creatinine ratio increased by 95% after 10-14 days of amikacin treatment. Serum Mg and Ca did not change notably after treatment, irrespective of initial Mg status. CONCLUSIONS: Aminoglycoside therapy in children with ALL is not associated with overt nephrotoxicity. A transient renal leak of Mg and Ca does occur. Screening of ALL children for mild hypomagnesemia may help to identify those most at risk of disruption of renal conservation of Mg and possibly Ca.

Adolescent↗
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↗
PubMed1993

Dyspermia in men with localized Hodgkin's disease. A potentially reversible, immune-mediated disorder.

Localized Hodgkin's disease (HD) is curable in the great majority of patients. However, common programs of chemotherapy for this disease render most men permanently azoospermic. In studies of seminal cryopreservation prior to treatment, it has been recognized that many men with HD are dyspermic at diagnosis. It is hypothesized that this abnormality reflects a change in the cellular regulation of spermatogenesis; specifically an alteration in the balance between distinct sub-populations of lymphocytes which normally either inhibit or stimulate the production of sperm. This change in regulation within the testes is believed to be part of a systemic perturbation which is unrelated to the extent of HD but is potentially reversible with effective treatment of the primary disease. Recognizing the distinction between sperm analyses and fertility status, it is proposed that radiotherapy of localized HD, delivered in a manner that is not toxic to the male gonad, will restore useful spermatogenesis in patients who are dyspermic (and probably subfertile) before treatment is initiated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

The comprehensive assessment of health status in survivors of childhood cancer: application to high-risk acute lymphoblastic leukaemia.

The health status of 69 survivors of high-risk acute lymphoblastic leukaemia (ALL) is assessed using a multi-attribute classification system. Seven attributes are included: sensation, mobility, emotion, cognition, self-care, pain and fertility. Three to five levels of functioning are defined for each attribute. Comprehensive health states are described as a specific combination of seven attribute levels. The system captures combinations of sequelae. The system provides a compact but comprehensive tool for long term follow up of survivors of childhood cancer. The results underscore the cognitive and emotional burdens of morbidity affecting survivors of high-risk ALL.

Cognition Disorders↗
PubMed1993

Acute lymphoid leukemia. No evidence of consistent chemotherapy-induced intestinal malabsorption.

PURPOSE: The impact of chemotherapeutic agents on intestinal functional integrity was assessed in 16 consecutive children treated for acute lymphoid leukemia (ALL) and in remission on maintenance therapy. PATIENTS AND METHODS: Measurements of height, weight, nutrient intake, fecal fat, D-xylose absorption, and lactose absorption were obtained at diagnosis and every 6 months during therapy. RESULTS: At diagnosis all children were age appropriate for height and weight. A decrease in height velocity occurred in 73% at 12 months and 29% at 24 months. A reduced weight velocity was seen in 40% at 12 months and 14% at 24 months. Nutrient intake was more than two thirds the recommended nutrient intake (RNI) for energy in 70% of the children and > 100% RNI for protein in all but one child. Gastrointestinal investigations at diagnosis were normal, and no child had symptoms suggestive of malabsorption. Fecal fat excretion was abnormal in only one child, after therapy-induced pancreatitis, and returned to normal with pancreatic enzyme supplementation. D-xylose absorption became abnormal in two children at 6 months on therapy, normalized at 12 months, and remained normal on further evaluations. Intestinal lactose absorption was abnormal in four of 12 children. CONCLUSIONS: These results suggest that habitual nutrient intake is adequate and that there is no generalized malabsorption in children during treatment for ALL that might interfere with their overall nutritional status. However, mild to moderate alteration in intestinal functional integrity may occur transiently in some children.

Adolescent↗
PubMed1993

An assessment of global health status in survivors of acute lymphoblastic leukemia in childhood.

PURPOSE: Progressive improvement in survival rates of children with cancer demands an appraisal of the "cost of cure." Much information is available on the frequency and severity of individual late effects in long-term survivors, but there are few data on multiple sequelae in individual patients or on global morbidity burdens. PATIENTS AND METHODS: To address this issue, we developed a multiattribute health status classification system. This consists of three to five levels of function within each of seven attributes: sensation, mobility, emotion, cognition, self-care, pain, and fertility. The system was applied to survivors of acute lymphoblastic leukemia (ALL). RESULTS: Overall burdens of morbidity were greater in those who had had "high-risk" disease than in children treated less intensively for "standard-risk" ALL. Deficits in emotional and cognitive status were especially common (alone and in combination). These were more prevalent in younger patients and exhibited a dose relationship to cranial irradiation. CONCLUSIONS: Such appraisals of morbidity must be compared with prevalence rates in the general population.

Activities of Daily Living↗
PubMed1993

Regulation of lithium and boron levels in normal human blood: environmental and genetic considerations.

Blood lithium levels may be both genetically and environmentally regulated. The genetic component is evidenced mainly from studies in twins who were either normal or had a manic-depressive disorder. An environmental contribution is adduced from the relationship between the blood lithium level and the amount of the element ingested. No such information is available for boron, another element present in ultra trace amounts in human blood. Unusually high levels of lithium and boron in the waters of northern Chile offer an opportunity to study the genetic and environmental regulation of these elements in the blood of healthy subjects. Samples of blood (n = 40) and water (n = 47) were collected at seven locations in the province of Tarapaca. Most of the healthy subjects were Aymara who had been resident in the respective communities for at least 3 years. The samples were transported to Canada and then freeze-dried. Neutron irradiation was performed in a highly thermalized flux to induce the reactions 6Li (n, alpha) t and 10B (n,7Li) alpha. Assays of 6Li and 10B were conducted in a static mass spectrometer by measurement, respectively, of 3He, produced from decay of tritium, and 4He from alpha-particles. Lithium concentrations in water and blood exhibited a linear relationship, as did the boron concentrations in these fluids. Because some of the individual subjects (n = 15) were first-degree relatives, a genetic component to the regulation of blood levels was explored. The variance in blood levels of lithium and boron was significantly greater between than within families (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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↗