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Biomedical subjects

J Radcliffe

Publications and source records attributed to J Radcliffe.

17 recordsLinked to original sources
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↗
PubMed1993

Mild Brachmann-de Lange syndrome. Delineation of the clinical phenotype, and characteristic behaviors in a six-year-old boy.

Brachmann-de Lange syndrome (BDLS) is a rare multiple congenital anomaly/mental retardation (MCA/MR) syndrome with variable expression, making diagnosis of mild cases difficult. The most consistent manifestations appear to be the characteristic face, which can be subtle in children who are mildly affected [Ireland and Burn, 1991: Twelfth Annual David W. Smith Workshop on Malformations and Morphogenesis]. Other aspects of the syndrome include variable degrees of mental retardation, growth retardation, structural abnormalities of the limbs, and behavior abnormalities, noted to be "autistic" [Jones, 1988: "Smith's recognizable patterns of human malformation"]. Johnson et al. [1976: Pediatr Res 10:843-850] described a behavior phenotype felt to be common in patients with BDLS. They predicted that patients with BDLS may respond to "behavioral intervention". Other behavior abnormalities in BDLS have been reported [Barr et al., 1971: Neuropadiatrie 3:46-66; Hawley et al., 1985: Am J Med Genet 20:453-459]. We report on a 6-year-old boy with the facial characteristics of BDLS, normal birth weight, prenatal onset of a small head relative to length, postnatal onset growth deficiency, nearly normal psychomotor development with onset of clear developmental delays by 2 years. He developed behavior problems similar to those seen in other patients with BDLS. These behaviors are most consistent with Pervasive Development Disorder-NOS (PDD), and Autistic Disorder [DSM-III-R, 1987] which encompasses a spectrum of mild to severe autistic behaviors. We report successful in-patient care utilizing medical and behavioral techniques to reduce the frequency of the behaviors. We feel that the presence of the characteristic behaviors may be helpful in confirming the diagnosis of BDLS.

Autistic Disorder↗
PubMed1993

Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas.

The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P < 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors secreting FSH (28-266%, P < 0.05) and increased alpha-su secretion in all four tumors studied (36%, 63%, 91%, and 121%, P < 0.05). IGF-1 reduced LH secretion in four/nine tumors (13%, 23%, 32%, and 50%, P < 0.05). Dose response curves (1-100 nmol/L IGF-1) were performed on three tumors cosecreting FSH and LH. Stimulation of FSH was achieved with either 1 or 10 nmol/L IGF-1, a single tumor in which alpha-su was measured showed maximal stimulation at 10 nmol/L IGF-1, and one of three tumors showed LH inhibition with 100 nmol/L IGF-1. In situ viability of attached cells was assessed with fluorescein and propidium iodide in seven tumors. After 4 days' exposure to 100 nmol/L IGF-1, in situ viability was increased in five tumors (range 12-19%, 15 +/- 1.3% SEM, P < 0.05). The effects of IGF-1 on the adenoma cell proliferative S-phase fraction was determined in six tumors after 4 days of treatment using double immunostaining with bromodeoxyuridine incorporation for 1 h. In four/six adenomas that stained positive for bromodeoxyuridine in the controls (1-5.6%), the S-phase fraction was increased by 100 nmol/L IGF-1 [(range 2.1-10.6%, increase 90-220%) (P < 0.05)]. These results show that IGF-1 has differential effects on gonadotropins from human pituitary adenomas, stimulating intact FSH and alpha-su, inhibiting or being without effect on intact LH in vitro, and increasing both viability and number of tumorous glycoprotein-secreting cells entering into the S-phase of proliferation.

Adenoma↗
PubMed1992

Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy.

Cognitive function and school achievement were studied prospectively over 3 to 4 years in 19 children treated for brain tumors with whole-brain radiotherapy; 14 of 19 also received adjuvant chemotherapy. For the group as a whole, mean IQ fell from a baseline of 104 to 92 at follow-up (p < 0.01). Age was inversely correlated with change in IQ over time (r = 0.71; p < 0.001). Children younger than 7 years at diagnosis had a mean IQ loss of 27 points, while children over 7 years at diagnosis showed no significant decrease in IQ. Decline in IQ occurred between baseline and year 2 of follow-up; none could be documented between years 2 and 4. All children younger than 7 years at diagnosis were receiving special education at follow-up; 50% of the children over 7 years at diagnosis were receiving supplemental educational services.

Adolescent↗
PubMed1992

Bone marrow transplantation for Niemann-Pick type IA disease.

Bone marrow transplantation has been undertaken with encouraging results as therapy for a wide variety of lysosomal storage diseases. We report a case of Niemann-Pick disease Type IA in which, despite the presence of only mild hypotonia with depressed reflexes, the clinical course of the disease appeared to be only slightly modified by this procedure, which was performed at the earliest practical opportunity. The patient was diagnosed early when asymptomatic, because of a family history of an affected sibling who died at 14 months. He received a bone marrow transplant from an HLA-identical, MLC non-reactive sibling donor, whose leukocyte sphingomyelinase activity was in the homozygote normal range. There was adequate engraftment as evidenced by persistently normal leukocyte sphingomyelinase activities, and there was no evidence of graft-versus-host disease. Visceral storage and neurological impairment were less rapidly progressive than in his untreated sibling but he eventually died at 30 months. Autopsy confirmed that this was essentially due to the effects of the underlying Niemann-Pick disease. We conclude that despite some success in other neurovisceral lysosomal storage disorders, bone marrow transplantation is not likely to be an adequate treatment for Niemann-Pick disease Type IA.

Bone Marrow Transplantation↗
PubMed1992

Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.

PURPOSE: Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline. PATIENTS AND METHODS: A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation. RESULTS: Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET. CONCLUSIONS: One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.

Adolescent↗
PubMed1990

Predicting IQ change in preschoolers with developmental delays.

This study examined IQ change over a 2-year period in 291 young children (mean age 39 months) referred to a pediatric developmental clinic for evaluation of developmental problems. Although correlation between initial and follow-up IQ was very high (0.78), there was also a significant increase in mean IQ score, from 67.12 to 74.06. Moreover, 26% of the subjects showed IQ increase of 16 points or more. Variables making some contribution to IQ change were initial clinical diagnosis, etiology, and intervention. Children diagnosed with a developmental language disorder made significantly greater gains than those diagnosed as mentally retarded. Sex, family status, initial age, and test interval were not significantly correlated with IQ change. We concluded that prediction for individual children is difficult, but that initial diagnosis may be useful in differentially predicting IQ change in young children with developmental delays.

Affective Symptoms↗
PubMed1990

The 1988-1989 decubitus study. Can a standardization of treatment be set for the elderly patient with decubiti ulcers stage III?

On July 1, 1988, a 6-month study began which included 15 ICF and SNF facilities and a census of approximately 1,300 patients. Forms and instructions were sent to each facility prior to the study. Stage II to Stage IV decubiti ulcers were reported on a monthly basis. Information obtained on all decubiti included: Nutritional intake, mental state, mobility, incontinence, contributing diagnoses, decubiti sizes and locations, recurrence of decubiti sites, stages, dates healed, cultures taken and reported, and treatments given. The completed forms were mailed into the Decubitus Study Committee every 3 months being due October 1, 1988 and January 1, 1989. The forms were designed to be as brief as possible yet provide the desired information.

Aged↗
PubMed1989

The relationship of play behavior to cognitive ability in developmentally disabled preschoolers.

The relationship of play behavior to cognitive functioning in preschool developmentally disabled children was studied by comparing performance on Lowe and Costello's Symbolic Play Test (SPT) with that on the Bayley Scales and Stanford-Binet Scale. Subjects were 247 children referred for evaluation to a hospital-based child development clinic. Subjects were classified as mildly retarded, moderately retarded, atypical, borderline, and language disordered. Correlations between the Bayley/Binet and SPT for the whole sample were significant and in the low to moderate range. Correlations between cognitive and play measures for each clinical group were in the low to moderate range, except for atypical children where the correlations were negligible. The retarded and borderline groups achieved similar mental ages on the Bayley/Binet and SPT, but the language-disordered and atypical groups demonstrated marked differences in their Bayley/Binet and SPT functioning. Implications for using the SPT in clinical practice were discussed.

Child Development Disorders, Pervasive↗
PubMed1989

A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results.

As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties. After CRT, children with brain tumors also demonstrated a fall in a wide range of achievement scores and an increased need, over time, for special help in school. The 2-year results of this study suggest that children with brain tumors treated with CRT are cognitively impaired and that these deficits worsen over time. The younger the child is at the time of treatment, the greater is the likelihood and severity of damage. These children, although not retarded, have a multitude of neurocognitive deficits which detrimentally affects school performance. New treatment strategies are needed for children with malignant brain tumors.

Adolescent↗
PubMed1988

Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update.

Chiasmatic/hypothalamic gliomas (CHG) of childhood may cause progressive neurological and visual deterioration. Radiotherapy results in at least transient stabilization of tumor growth in most patients but may also have adverse long-term effects, especially in young children. Since 1977, children with progressive CHG under 5 years of age at diagnosis have been treated with combination chemotherapy (actinomycin D and vincristine) without radiotherapy. Twenty-four patients, a median of 1.6 years of age at diagnosis, have been treated and followed for a median of 4.3 years (range, 0.3-10 years). All patients are alive. Nine have developed radiographic or clinical progression, occurring a median of 3 years (range, 2-6.5 years) after initiation of treatment. Fifteen of 24 (62.5%) have remained free of progressive disease and have received no other therapy. Tumor shrinkage was documented in 9 of 24 patients but did not clearly relate to long-term outcome. Full-scale intelligence quotient (IQ) obtained a median of 3.5 years after diagnosis in patients who received only chemotherapy was a mean of 103 (range 84-133). We conclude that chemotherapy can significantly delay the need for radiotherapy in children with CHG and such a delay may be beneficial regarding long-term outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The asymptotic speed of propagation of the deterministic non-reducible n-type epidemic.

A model has been formulated in to describe the spatial spread of an epidemic involving n types of individuals, when triggered by the introduction of infectives from outside. Wave solutions for such a model have been investigated in and have been shown only to exist at certain speeds. This paper establishes that the asymptotic speed of propagation, as defined in Aronson and Weinberger, of such an epidemic is in fact c0, the minimum speed at which wave solutions exist. This extends the known result for the one-type and host-vector epidemics.

Biometry↗
PubMed1984

A comparison of clonidine and standard provocative agents of growth hormone.

To evaluate the effectiveness of clonidine on growth-hormone (GH) release in prepubertal children, and to distinguish between a central alpha-adrenergic effect and a corticotropin-cortisol-mediated response, we measured serum glucose, corticotropin, cortisol, and GH concentrations following levodopa, arginine hydrochloride, and clonidine hydrochloride stimulation in 15 euthyroid children who had short stature. We found that clonidine is an effective and safe stimulator of GH release and provided a clearer distinction between GH-deficient and non-GH-deficient young persons than levodopa or arginine. The action of clonidine is not corticotropin-cortisol mediated.

Adolescent↗
PubMed1984

The uniqueness of wave solutions for the deterministic non-reducible n-type epidemic.

In a recent paper, [8], we investigated the existence of wave solutions for a model of the deterministic non-reducible n-type epidemic. In this paper we first prove two properties left as an open question in that paper. The uniqueness of the wave solutions at all speeds for which a wave solution exists is then established. Only an exceptional case is not covered.

Disease Outbreaks↗
PubMed1984

The spatial spread and final size of the deterministic non-reducible n-type epidemic.

A model has been formulated in [6] to describe the spatial spread of an epidemic involving n types of individual, and the possible wave solutions at different speeds were investigated. The final size and pandemic theorems are now established for such an epidemic. The results are relevant to the measles, host-vector, carrier-borne epidemics, rabies and diseases involving an intermediate host. Diseases in which some of the population is vaccinated, and models that divide the population into several strata are also covered.

Animals↗
PubMed1983

Wave solutions for the deterministic non-reducible n-type epidemic.

A model is formulated to describe the spatial spread of an epidemic involving n types of individual. This encompasses the measles, host-vector and carrier-borne epidemics, and in addition rabies involving several species of animal. The existence, uniqueness and non-existence of wave solutions for different speeds are established for this model.

Animals↗