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Biomedical subjects

J Radcliffe

Publications and source records attributed to J Radcliffe.

At least 19 recordsLinked to original sources
PubMed2001

The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead.

BACKGROUND: Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment. METHODS: We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months. RESULTS: During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter [0.2 to 0.3 micromol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant. CONCLUSIONS: Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 microg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels.

Chelating Agents↗
PubMed2000

The early fall in levels of S-100 beta in traumatic brain injury.

Protein S-100 beta has been suggested as a prognostic marker in traumatic brain injury. However, little is known of its behaviour in the immediate post-injury period. With Ethics Committee approval, we recruited 30 patients with a history of head injury presenting to our Accident and Emergency Department. Blood was taken on arrival and at four hours post-injury. Serum S-100 beta was estimated using an immunoluminometric assay. Levels of S-100 beta were seen to fall rapidly with time. Half-time was distributed non-parametrically with a median of 198 minutes. Using the Mann-Whitney U test we found a statistically significant difference between non-desirable (Glasgow Outcome Score 1-3) and desirable (Glasgow Outcome Score 4-5) outcome on admission (p = 0.0155) but not at four hours (p = 0.1336). Levels of S-100 beta fell rapidly after its release following traumatic brain injury. Time after injury is therefore critical in assessing the significance of levels of S-100 beta, and sampling should be as early as possible to gain maximum information. If S-100 beta is to be assessed as a monitor of ongoing brain injury in the intensive therapy unit sampling must be frequent (e.g. every 4 hours) to be able to detect rises in serum levels before they have decayed to baseline.

Brain Injuries↗
PubMed1999

The derivation of certain pandemic bounds.

Exact results have previously been obtained concerning the spread of infection in continuous space contact models describing a class of multitype epidemics. The Pandemic Theorem gave a lower bound for the spatial final size. A discrete space model is considered. A simpler, more direct proof based on an infinite matrix formulation of the final size equations is used to obtain the pandemic result for this model. An upper bound is obtained, which is valid for both continuous and discrete space models. This enables a limiting result to be obtained for the spatial final size when the amount of initial infection tends to zero.

Epidemiology↗
PubMed1999

Strategic and genetic models of evolution.

A new model which allows both for the effect of behavioural patterns on productive matings and for parental investment in the survival of offspring to maturity is considered. This combines ideas from genetics and evolutionary game theory, and provides a more realistic formulation to describe mating behaviour than the traditional 'battle of the sexes' model. Allowing individuals to migrate leads to spatial versions of both models. The saddle point method is used to obtain the speed of first spread of new genes/strategies in both spatial systems.

Biological Evolution↗
PubMed1999

Effect of dietary fish oil on tumor-induced hyperlipidemia and tumor growth in rats implanted with a methylcholanthrene-induced sarcoma.

Male Fischer 344 rats implanted with a methylcholanthrene-induced sarcoma (MCS), along with normal (or control) animals, were fed diets containing either 10% com oil (CO) or 2% CO + 8% fish oil (FO), designated as diets CO and FO, respectively, in a study designed to determine the effect of dietary FO on serum lipids (in the presence or absence of a tumor) and the growth and fatty acid composition of the MCS. For both diets, MCS-bearing rats had significantly (p < 0.05) higher serum levels of triglycerides, cholesterol, phospholipids, and total lipids than controls. For both controls and tumor-bearers, serum levels of all these lipids were, with the exception of cholesterol for the tumorbearers, significantly lower in rats receiving the FO diet than for the corresponding groups receiving the CO diet. Relative to rats fed the CO diet, those fed the FO diet had significantly higher serum levels of some fatty acids (e.g., 20:5n-3) but significantly lower levels of others (e.g., 18:2n-6), regardless of tumor status. For the tumor-bearers, differences in the levels of fatty acids in MCS tissue reflected differences in the fatty acid composition of total serum lipids. Sarcoma growth was unaffected by diet. Thus, feeding dietary FO resulted in changes in the lipid status of both control and tumor-bearing rats. Since sarcoma growth was unaffected by diet, the reduction in the severity of MCS-induced hyperlipidemia by FO appears to be due to an effect of the oil per se.

Animals↗
PubMed1999

Family functioning, neurocognitive functioning, and behavior problems in children with sickle cell disease.

OBJECTIVE: To investigate the independent and combined contributions of neurocognitive and family functioning to mother-reported behavior problems in children with sickle cell disease (SCD) and evaluate the factor structure of the Family Environment Scale (FES) with African American families. METHOD: The study sample included 289 children enrolled in the multisite Cooperative Study of Sickle Cell Disease. The study protocol included neuropsychological evaluation and brain magnetic resonance imaging (MRI) of the children, and mothers completed the Child Behavior Checklist and Family Environment Scale. RESULTS: With child and maternal demographic parameters controlled, conflicted family functioning, but not neurocognitive functioning, accounted for a significant portion of the variance in mother-reported behavior problems. The factor structure of the FES for families of children with SCD was found to be similar to that for other families. CONCLUSIONS: Family functioning may be a salient target for fostering adaptation to chronic childhood illness.

Adaptation, Psychological↗
PubMed1999

Quality of life of adult survivors of germinomas treated with craniospinal irradiation.

OBJECTIVE: To assess the quality of life (QOL) of a group of patients treated for intracranial germinoma with biopsy followed by prophylactic whole-neuraxis radiation therapy. METHODS: The Short-form-36 and Functional Assessment of Cancer Therapy QOL questionnaires were completed by 22 of 27 eligible adults treated with whole-neuraxis irradiation for biopsy-proven, marker-negative intracranial germinomas between 1976 and 1996. In addition, data were obtained regarding height and weight, medications, ability to work, and educational achievement. RESULTS: The patients' QOL was generally good. All of the patients are in or have completed high school; nine are in or have completed college, and five have advanced degrees. Patients rated themselves lower on the physical composite scale of the Short-form-36 (average, 46 versus 54 in a normal population). On the mental composite scale, patients rated themselves more favorably than the normal population (average, 54 versus 49 in a normal population). Patients were normally proportioned for height and weight, but female patients tended to be short. Age at radiation did not correlate with QOL. CONCLUSION: The QOL of adults treated for marker-negative germinoma with prophylactic whole-neuraxis irradiation is generally good. These data should serve as a benchmark for newer treatment protocols eliminating or reducing radiation.

Achievement↗
PubMed1998

Spatial Mendelian games.

This paper considers complex models arising in sociobiology. These combine genetic and strategic aspects to model the effect of gene-linked strategies on the ability of individuals to survive to maturity, mate and produce offspring. Several important models considered in the literature are generalised and extended to incorporate a spatial aspect. Individuals are allowed to migrate. Contests, e.g. for food or amongst males for females, take place locally. The choice of the point at which the population structure is measured affects the complexity of the equations describing the system, although it is possible to utilise any point in the life cycle. For our spatial models the simplest approach is to measure the population structure immediately after migration. A saddle point method, developed by the authors, has previously been used to obtain results for simple discrete time spatial models. It is utilised here to obtain the speed of first spread of a new gene-linked strategy for the much more complex sociobiological models included in this paper. This demonstrates the wide-ranging applicability and power of the method.

Alleles↗
PubMed1997

Keeping ahead.

Explore the source record for details and available documents.

Conflict of Interest↗
PubMed1997

Discrete time spatial models arising in genetics, evolutionary game theory, and branching processes.

A saddle point method is used to obtain the speed of first spread of new genotypes in genetic models and of new strategies in game theoretic models. It is also used to obtain the speed of the forward tail of the distribution of farthest spread for branching process models. The technique is applicable to a wide range of models. They include multiple allele and sex-linked models in genetics, multistrategy and bimatrix evolutionary games, and multitype and demographic branching processes. The speed of propagation has been obtained for genetics models (in simple cases only) by Weinberger and Lui, using exact analytical methods. The exact results were obtained only for two-allele, single-locus genetic models. The saddle point method agrees in these very simple cases with the results obtained by using the exact analytic methods. Of course, it can also be used in much more general situations far less tractable to exact analysis. The connection between genetic and game theoretic models is also briefly considered, as is the extent to which the exact analytic methods yield results for simple models in game theory.

Alleles↗
PubMed1996

Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma).

PURPOSE: Children under 5 years old with medulloblastoma (MB) have a poor prognosis. They are more susceptible to the deleterious effects of craniospinal irradiation (CSART) and have a higher relapse rate when treated with low-dose CSART alone. We, thus, embarked on a prospective trial testing the usefulness of very low dose CSART and adjuvant chemotherapy. This is an update of a previous report on these patients. METHODS AND MATERIALS: Between January 1988 and March 1990, 10 patients with medulloblastoma were treated using 18 Gy radiation therapy (RT) to the craniospinal axis, a posterior fossa (PF) boost to 50.4-55.8 Gy and chemotherapy consisting of vincristine (VCR) weekly during RT. This was followed by VCR, cis-diamminedichloroplatinum (CDDP), and lomustine (CCNU) for eight, 6-week cycles. Patients between 18 and 60 months of age without evidence of tumor dissemination were eligible for study. Follow-up was available until September 1994 with a median follow-up for living patients of 6.3 years from diagnosis. RESULTS: Actuarial survival at over 6 years is 70 +/- 20%. Three of the 10 patients relapsed and died. In one patient, the relapse developed in the spine and brain outside the posterior fossa, in the second, concurrently in the posterior fossa, brain and spine, and the third, only in the spine. One surviving child developed a brain stem infarct 4.8 years after diagnosis and has since almost fully recovered. A mean intelligence quotient (IQ) score of 103 in six patients surviving at least 1 year is unchanged from the baseline group score of 107. Five children tested at baseline and 2 years following treatment had IQ scores of 101 and 102, respectively. Six children tested at baseline and at 3 years had IQ scores of 106 and 96, respectively. Excluding the child tested shortly after his brain stem infarct, baseline and 3 year IQ scores were 103 and 97, respectively. Five of the seven long-term survivors grew at rates significantly below their expected velocities during the follow-up period, while the others grew normally. Three patients have received growth hormone, and none have required thyroid replacement. CONCLUSIONS: These data suggest that medulloblastoma patients can be cured with chemotherapy and reduced doses of craniospinal irradiation. The low doses of CSART given by us in conjunction with cis-platin-based chemotherapy produce minimal neurocognitive damage. Growth velocities in very young children so treated are, however, dramatically reduced. Better means of improving the therapeutic ratio are still needed.

Age Factors↗
PubMed1996

Adjustment in childhood brain tumor survival: child, mother, and teacher report.

Examined the adjustment of 6- to 18-year-old children and adolescents (n = 38) 2 to 5 years postdiagnosis of brain tumor with respect to standardized measures of anxiety and depression; self-perceptions; and adaptive living skills. Child, mother, and teacher report data were used. Maternal adjustment (anxiety and depression, parenting stress) was also assessed. Children and adolescents surviving brain tumors reported themselves to be generally within the normal range. However, maternal ratings of social problems were higher than normative scores and significantly lower than norms on social problems, scholastic competence, and communication skills. Teacher ratings on the Teacher Rating Form were all within normal limits. Maternal adjustment measures were within the normal range, although the Parent-Child Dysfunctional Interaction subscale of the Parenting Stress index was elevated. No differences in scores were found between children in regular and special education, or between children who had received radiation and those who did not. This sample of survivors of pediatric brain tumors and their mothers had relatively mild problems in adjustment, supporting a competency-based view of the adaptation of pediatric patients and their families.

Adaptation, Psychological↗
PubMed1995

Optic pathway and hypothalamic/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-up.

BACKGROUND: Gliomas of the hypothalamus and optic pathways (H/OPG) comprise 5% of pediatric intracranial tumors, present most frequently in patients younger than age 5 years, and may have a more aggressive course in younger children. This study examined clinical characteristics and consequences of treatment of young children diagnosed with H/OPG: METHODS: The authors reviewed the course, treatment, and outcomes of 46 children diagnosed with H/OPG younger than age 5 years; the median follow-up was 72 months. The median age at diagnosis was 27 months. RESULTS: Fifteen (33%) of 46 patients had neurofibromatosis-1 (NF-1). Forty children (87%) had tumor progression in the follow-up period, and tumor growth was less common in children with NF-1. Initial therapy was limited to surgical resection in three and radiation in five children. To postpone radiation until after the age of 5 years, initial therapy was limited to chemotherapy in 32 patients. Radiation was not required in 9 of these patients and was postponed for 40 months (mean) in 17. Of the 46 children, 5 died of tumor progression, 4 became blind, and 20 of 34 evaluable patients had endocrine abnormalities. Endocrinopathy did not correlate with therapy. Ten of 17 children evaluated by questionnaire required special education. There was a trend for educational problems to occur in children who were irradiated before the age of 5 years. CONCLUSIONS: Gliomas of the hypothalamus and optic pathways and their treatment cause long term morbidity in young children. Chemotherapy postpones radiation effectively, and this delay may reduce neurologic morbidity; however, 60% of children eventually relapse. By contrast, patients with NF-1 have indolent disease.

Child Behavior Disorders↗
PubMed1995

Effects of basic fibroblastic growth factor on the function and proliferation of human clinically non-functional pituitary adenomas which secreted glycoprotein hormones in vitro.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.

Adenoma↗
PubMed1994

The impact of perioperative factors on subsequent intelligence quotient deficits in children treated for medulloblastoma/posterior fossa primitive neuroectodermal tumors.

BACKGROUND: Despite success in treating children with medulloblastoma/posterior fossa primitive neuroectodermal tumor (PF PNET), some children survive with significant neurocognitive sequelae. This study was performed to understand better the significance of perioperative factors on subsequent full scale intelligence quotient (FSIQ) deterioration in these children. METHODS: Twenty-eight children who underwent prospective and serial neurocognitive testing were studied. All children underwent surgery followed by radiotherapy with or without chemotherapy between 1983 and 1987 for medulloblastoma/PF PNET and were disease free when this study was conducted. IQ testing was performed before surgery and after the completion of radiation therapy. The clinical courses of the patients were correlated with changes in the corresponding intelligence quotients of each child. Factors correlating with neurocognitive declines were examined by chi-square or Fisher exact test analysis. Differences in mean IQs were examined by the t test. Factors found to be significant were analyzed by exact logistic regression analysis. RESULTS: The presence of adverse factors such as neurologic deficits, meningitis, or shunt infections, or the need for repeat surgery was correlated significantly with IQ deficits after treatment. Of the subset of children with one or more of these factors, 13 of 16 (81%) sustained decreases in FSIQ; 7 of 16 (43.8%) had decreases of 20 points of more. In contrast, only 3 of 12 (25%) of the children without the factors sustained FSIQ decreases, and no child sustained a decrease of more than 13 points. The mean FSIQ change after treatment in the group with factors was -15.7 (95% confidence interval [CI]: -24.0, -8.4), and the median was -18. The mean FSIQ change in the group without factors was 4.8 (95% CI: -0.5, 10.1), and the median was 5. The difference in mean FSIQ change between the two groups was significant (P < 0.0001). On univariate analysis, both the presence of adverse factors and an age less than six years correlated with neurocognitive deficit. On regression analysis, only the presence of adverse factors was significant (odds ratio 11.53; 95% CI, 1.65-116.58; P = 0.009), whereas age was not (P = 0.27). CONCLUSIONS: Perioperative events or complications may account for some of the neurocognitive deterioration seen in these children after treatment, especially in the very young. The occurrence of these factors is associated with a significantly greater risk of IQ deterioration. Studies of the neurocognitive effects of treatment for children with medulloblastoma/PF PNET should include an analysis of these postoperative factors.

Adolescent↗