Search PubMed⌕ Search

Biomedical subjects

P Wilton

Publications and source records attributed to P Wilton.

At least 37 records · Page 2Linked to original sources
PubMed1999

Long-term treatment of growth hormone insensitivity syndrome with IGF-I. Results of the European Multicentre Study. The Working Group on Growth Hormone Insensitivity Syndromes.

A total of 33 patients (17 female, 16 male) with Laron syndrome (n = 31) or hGH-1 gene (n = 2, type IA deletion) from 22 centres in 12 countries were enrolled in a study conducted by Pharmacia & Upjohn, Stockholm, which was designed to test the efficacy, in terms of growth promotion and safety, of IGF-I (Igef(TM)). The patients were treated with 40-120 microg/kg IGF-I s.c. twice daily after meals. After the study ended, the patients continued to be treated on an individual basis. The results of 17 patients, who were treated for 48 months or longer were available for the present analysis. Six patients were treated for up to 72 months. When treatment started, the mean age of these patients (8 female, 9 male) was 9.1 (3.7-13.5) years and mean height was -6.5 +/- 1.3 SDS. At the end of the observation period, the mean age of the 17 patients was 14.2 (9.1-17. 7) years and mean height was -4.9 +/- 1.9 SDS. All patients showed a significant increase in growth during the final year on IGF-I, with two of them reaching the age-corresponding 3rd centile. The total gain in height (DeltaHT) was 1.7 +/- 1.2 SDS. DeltaHT SDS correlated negatively with age at onset of treatment (R(2) = -0.78, p < 0.02). BMI was 0.6 +/- 1.8 SDS at start of treatment and 1.8 +/- 1.5 SDS at the end of observation. Total DeltaHT SDS correlated positively with total DeltaBMI SDS (R(2) = 0.59, p < 0.01). Long-term treatment of patients with GHIS thus proved to be effective in promoting growth. If treatment is started at an early age, there is considerable potential for achieving height normalisation. The treatment modalities need to be optimized with respect to the growth-promoting and metabolic effects of IFG-I.

Adolescent↗
PubMed1999

The effects of treatment and the individual responsiveness to growth hormone (GH) replacement therapy in 665 GH-deficient adults. KIMS Study Group and the KIMS International Board.

Data from 665 adults with GH deficiency (GHD; 332 women; 169 childhood-onset GHD; mean age, 44 yr) were analyzed to determine the efficacy of and individual responsiveness to GH replacement therapy. GH replacement was started at enrolment into KIMS (Pharmacia & Upjohn, Inc. International Metabolic Database). Mean maintenance doses of GH after 6 and 12 months were 0.43 and 0.53 mg/day (1.3 and 1.6 IU/day) for men and women, respectively. Serum insulin-like growth factor I (IGF-I) SD score increased from -2.2 and -4.2 in men and women, respectively, to 1.8 and -0.9 at 6 months and 0.8 and -0.7 at 12 months. The waist/hip ratio decreased after 6 and 12 months, with the changes more pronounced in men. The waist/hip ratio was not influenced by age of onset of GHD, severity of hypopituitarism, or gonadal status. Total cholesterol decreased significantly in men, and high density lipoprotein cholesterol increased in women. Systolic blood pressure was unchanged during GH therapy, but diastolic blood pressure decreased in women. Quality of life, determined by a specific questionnaire for assessment of GHD in adults, improved after 6 and 12 months of GH therapy; this was more pronounced in adult-onset than in childhood-onset GHD, but was not influenced by gender, severity of hypopituitarism, or gonadal status. In 80% of patients, the starting dose of GH was 0.27 mg/day or less. This and the absence of a correlation between body weight and change in IGF-I were consistent with a dose-titration approach, which would tend to obscure individual variations in responses (determined by IGF-I levels). Nonetheless, the increase in IGF-I was significantly higher in men than in women on similar mean GH doses. Weak correlations were observed between the maintenance dose of GH and the change in IGF-I in men and women receiving sex steroid replacement, but not in patients with untreated hypogonadism or an intact gonadotropin reserve. Similarly, the increment in IGF-I was not related to the severity of GHD, as determined by the number of additional pituitary hormone deficiencies. Differences in IGF-I generation may partly explain the gender differences in reduction of central adiposity. These data highlight the value of large longitudinal surveillance databases in defining the optimum dose regimen for GH replacement and indicate that women may need a higher replacement dose of GH than men.

Adult↗
PubMed1999

Derivation and validation of a mathematical model for predicting the response to exogenous recombinant human growth hormone (GH) in prepubertal children with idiopathic GH deficiency. KIGS International Board. Kabi Pharmacia International Growth Study.

Postmarketing surveillance studies of recombinant human GH therapy, such as the Kabi Pharmacia International Growth Study (KIGS; Pharmacia & Upjohn, Inc., International Growth Database), have accumulated extensive data concerning the characteristics and growth outcomes of children with various causes of short stature. These data provide an opportunity to analyze the factors that determine responsiveness to GH and allow the development of disease-specific growth prediction models. We undertook a multiple regression analysis of height velocity (centimeter per yr) with various patient parameters of potential relevance using data from a cohort of 593 prepubertal children with idiopathic GH deficiency (GHD) from the KIGS database. Our aim was to produce models that would have practical utility for predicting prepubertal growth during each of the first 4 yr of GH replacement therapy. These models were validated by a prospective comparison of predicted and observed growth outcomes in an additional 3 cohorts of prepubertal children with idiopathic GHD: 237 additional KIGS patients, 29 patients from the Australian OZGROW study, and 33 patients from Tubingen, Germany. The most influential variable for first year growth response was the natural log (ln) of the maximum GH response during provocation testing, which was inversely correlated with height velocity. The first year growth response was also inversely correlated with chronological age and height SD score minus midparental height SD score. First year growth was positively correlated with body weight SD score, weekly GH dose (ln), and birth weight SD score. Two first year models were developed using these parameters, 1 including and 1 excluding the maximum GH response to provocative testing. The former model explained 61% of the response variability, with a SD of 1.46 cm; the latter model explained 45% of the variability, with a SD of 1.72 cm. The two models gave similar predictions, although the model excluding the maximum GH response to testing tended to underpredict the growth response in patients with very low GH secretory capacity. For the second, third, and fourth year growth responses, 4 predictors were identified: height velocity during the previous year (positively correlated), body weight SD score (positively correlated), chronological age (negatively correlated), and weekly GH dose (ln; positively correlated). The models for the second, third, and fourth year responses explained 40%, 37%, and 30% of the variability, respectively, with SDs of 1.19, 1.05, and 0.95 cm, respectively. When the models were applied prospectively to the other cohorts, there were no significant differences between observed and predicted responses in any of the cohorts in any year of treatment. The fourth year response model gave accurate prospective growth predictions for the fifth to the eighth prepubertal years of GH treatment in a subset of 48 KIGS patients. Analyses of Studentized residuals provided further validation of the models. The parameters used in our models do not explain all of the variability in growth response, but they have a high degree of precision (low error SDs). Moreover, the parameters used are robust and easily accessible. These properties give the models' practical utility as growth prediction tools. The availability of longitudinal, disease-specific models will be helpful in the future for enabling growth-promoting therapy to be planned at the outset, optimized for efficacy and economy, and individualized to meet treatment goals based on realistic expectations.

Child↗
PubMed1998

Growth hormone replacement and the risk of malignancy in children with neurofibromatosis.

OBJECTIVE: To assess the efficacy and safety of growth hormone (GH) therapy in children with GH deficiency in association with neurofibromatosis. METHODS: Retrospective analysis of data from the Pharmacia and Upjohn International Growth Database (KIGS) in a total of 102 GH-deficient children with neurofibromatosis treated with recombinant GH. RESULTS: Median pretreatment height velocity was 4.2 cm/yr (1.7 to 6.4 cm/yr), increased to 7.1 cm/yr (4.6 to 10.0 cm/yr) in the first year of GH therapy, and remained significantly greater than pretreatment at 5.7 cm/yr (2.9 to 8.3 cm/yr) and 5.7 cm/yr (2.6 to 7.9 cm/yr) in the second and third years, respectively. The median height SD score increased from -2.4 to -1.8 by the end of 3 years of treatment. Five patients had either a recurrence of an intracranial tumor or a second intracranial tumor; this incidence of tumor occurrence is comparable to that reported previously in similar patients with neurofibromatosis. Other adverse events were relatively minor and unlikely to be attributable to GH therapy CONCLUSIONS: The data indicate that GH replacement therapy, per se, for patients with neurofibromatosis and GH deficiency is likely to be beneficial and unassociated with excessive malignant risk.

Adolescent↗
PubMed1998

Primary care reform: a three country comparison of 'budget holding'.

Governments in most developed nations have been looking to organisational and financial reform of health systems over the last decade. Although the structure and problems of the health care sector in each country may differ, with countries correspondingly adopting different reform agendas, there has been some element of commonality in reforms: that of (managed) competition. Of particular importance in such reforms has been the strengthening of primary care. General practitioners and primary care physicians, as 'gatekeepers' to the health system, are increasingly being called upon to be accountable; not only for their patients' health but also for the wider resource implications of any treatments prescribed. In some countries this role has been formalised through establishing 'budget holding' for general practitioners and primary care physicians, for example, through general practice 'fund holding' in the UK, Health Maintenance Organisations in the USA, and Independent Practice Associations in New Zealand. This paper examines: (i) what such budget holding seeks to achieve; (ii) the effectiveness of the budget holding experience to date in achieving these objectives; and (iii) factors which appear to determine the success of budget holding in achieving its objectives.

Budgets↗
PubMed1998

Growth hormone replacement in patients with Langerhan's cell histiocytosis.

OBJECTIVES: To assess the impact of growth hormone on growth and the underlying disease in children with growth hormone deficiency as a result of Langerhan's cell histiocytosis. STUDY DESIGN: Retrospective analysis of data from the Kabi (Pharmacia & Upjohn) international growth database (KIGS) for 82 children with Langerhan's cell histiocytosis treated with recombinant growth hormone. RESULTS: At the start of treatment the median (10-90th centile) age was 9.0 (5.2 to 14.7) years, with a median height standard deviation score (SDS) of -2.0 (-3.5 to -0.9). The median pretreatment height velocity (measured in cm/year) was 3.6 (0.9 to 6.4); this increased to 8.8 (3.8 to 12.0) in the first year of treatment with growth hormone, and then remained significantly greater than the pretreatment height velocity at 7.3 (4.4 to 9.7) and 7.1 (4.1 to 9.3) cm/year in the second and third years, respectively. The median height SDS increased from -2.0 to -0.8 (-2.3 to 0.6) by the end of three years of treatment. There was no increase in the recurrence rate of the underlying disease and no adverse event could be directly attributed to growth hormone treatment, apart from one case of benign intracranial hypertension that resolved on stopping treatment with growth hormone. CONCLUSIONS: Growth hormone replacement treatment for patients with Langerhan's cell histiocytosis with growth hormone deficiency is beneficial and safe.

Adolescent↗
PubMed1998

Efficacy and safety of growth hormone treatment in children with prior craniopharyngioma: an analysis of the Pharmacia and Upjohn International Growth Database (KIGS) from 1988 to 1996.

We studied short- and long-term responses to growth hormone (GH) treatment and adverse medical events (AE) in 488 patients with craniopharyngioma who were entered into the Kabi International Growth Study (KIGS). First-year growth response and responsiveness (n = 394) were similar to those seen in children with idiopathic GH deficiency. The growth response over 5 years (n = 152) was unaffected by the recurrence of tumour and prior tumour management, but was greater in those receiving thyroxine. Mean height standard deviation scores (SDS) at the end of GH treatment (n = 129) was -0.7+/-1.2, and 79% achieved a height over -2 SD of target height, with evidence of further growth potential. Final height SDS correlated positively with height SDS at the start of treatment and with target height SDS, whereas gain in height SDS was inversely correlated with height SDS and bone age at the start of GH treatment. The rate of recurrence of tumour, 0.045/treatment year, was greater in those who had been treated with surgery alone compared to surgery and cranial irradiation. Other AE included headaches, fluid retention and convulsions occurring at rates of 0.025, 0.005 and 0.004/treatment year, respectively. We concluded that GH treatment is safe and effective in children with craniopharyngioma and provide data for counselling of parents about outcome during GH treatment.

Body Height↗
PubMed1998

General practice fundholding: progress to date.

BACKGROUND: The cornerstone of the National Health Service (NHS) reforms was the establishment of an internal market, which separated purchasing and providing roles. As purchasers of care, general practice fundholders were seen as a pivotal part of the 'new patient-led NHS', which was intended to lead to improved cost-containment and cost-effectiveness, quality of care, and patient choice and empowerment. AIM: To review published evidence of the extent to which these objectives may have been achieved over the past six years. METHOD: Keyword search of on-line databases (MEDLINE and Econ-lit) from 1990 to 1996, plus manual search of references within those articles identified. RESULTS: In the absence of any formal evaluation of fundholding, it is difficult to assess the overall success of this reform. However, in terms of cost-containment and cost-effectiveness, there is mixed evidence. In some areas, such as prescribing, the evidence suggests cost-savings, although the evidence is less clear on reductions or changes in referrals. There is also evidence that suggests that improvements in prescribing may have been achieved at substantial additional administration and transaction costs. With respect to quality of care, the evidence suggests that, although quality in the procedural aspects of health provision has improved, there is little evidence about how health outcomes may have been affected. In terms of patient choice and empowerment, the evidence suggests that, whilst general practitioner choice of secondary providers has improved, little progress has been made with regard to increased consumer choice. CONCLUSION: Evidence concerning the success or otherwise of general practice fundholding over the past six years is incomplete and mixed. The major deficiency concerns any effect on health outcomes that may be the result of fundholding. Until such research is conducted, the jury will have to remain out on whether fundholding has secured improved efficiency in the delivery of health care.

Contract Services↗
PubMed1997

Growth hormone treatment induces a dose-dependent catch-up growth in short children born small for gestational age: a summary of four clinical trials.

In the present study, data from 230 short children born small for gestational age, who were participating in four clinical trials, were pooled and analysed. At the start of GH treatment, median age and height SDS were 5.3 years and -3.2 SDS, respectively. A dose-dependent increase in height SDS was observed following 2 years of GH treatment: 1.1, 1.7 and 2.5 SDS for the three GH treatment groups (0.1, 0.2 and 0.3 IU/kg/day, respectively), compared with an increase of 0.14 SDS in the control group. In a multiple regression analysis, four variables were found to correlate independently with the gain in height SDS following 2 years of GH treatment. These are given below in order of importance: gain in height SDS = 7.7 x dose of GH (IU/kg/day) -0.11 x age (years) -0.08 x parental-adjusted height SDS + 0.05 x birth length SDS (SD = 0.5; r2 = 0.64). At the end of the 2-year study period, a total of 48%, 66% and 90% of patients in the groups given GH at 0.1, 0.2 and 0.3 IU/kg/day, respectively, had a parental-adjusted height greater than -1.0 SDS.

Body Height↗
PubMed1996

Eye bank's success due to vision of its founders.

In 1955, the Eye Bank of Canada introduced Canadians to the idea of postmortem tissue donation. The long-time administrator of the bank's Ontario Division, Anne Wolf, recalls the organization's early days and how the management of donated corneas became a family affair.

Canada↗
PubMed1996

Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies.

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children (n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age, GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.

Age Determination by Skeleton↗
PubMed1995

Cod-liver oil, vitamin D and the fight against rickets.

Although rickets has all but disappeared as a medical problem, the disease caused serious concern in turn-of-the-century England, where it reached epidemic proportions. The connection between rickets and a lack of vitamin D wasn't made until shortly after World War I, when it was determined that regular exposure to sunlight would eliminate the problem; another solution was to provide vitamin D supplements in milk. The problem hasn't disappeared entirely, however. Seventeen cases of rickets have been diagnosed at Toronto's Hospital for Sick Children in the past 5 years.

Cod Liver Oil↗
PubMed1995

Recombinant human insulin-like growth factor-I decreases serum lipoprotein(a) concentrations in normal adult men.

OBJECTIVE: Lipoprotein(a) is a lipoprotein fraction associated with atherosclerosis. The serum concentration of lipoprotein(a) has been shown to be mainly genetically determined but recently evidence for hormonal regulation has been presented. The aim of the present study was to investigate the effects of insulin-like growth factor-I on serum lipoproteins, especially lipoprotein(a). DESIGN: The effects of one week of IGF-I treatment were studied in an open trial. SUBJECTS: Ten healthy men, who participated in a pharmacokinetic study, were given recombinant human insulin-like growth factor-I (40 micrograms/kg/day) as daily subcutaneous injections. MEASUREMENTS: Serum samples for measurements of lipoproteins were taken after an overnight fast before and after 7 days of treatment. RESULTS: There was decrease in serum lipoprotein(a) concentration (18.5 +/- 5.5%) in nine of the subjects, and a slight increase in one of the subjects with the lowest concentrations. Also serum apolipoprotein (b) (6.3 +/- 2.2%), serum cholesterol (10.6 +/- 1.8%) and serum triglyceride (14.8 +/- 4.8%) concentrations decreased. An unexpected finding was that fasting serum glucose concentrations increased (13 +/- 4%). CONCLUSION: Insulin-like growth factor-I is involved in the regulation of lipoprotein(a) concentrations, which might have novel therapeutic implications.

Adult↗
PubMed1995

Insulin-like growth factor I improves height in growth hormone insensitivity: two years' results.

Thirty-one patients with growth hormone insensitivity syndrome (GHIS) and 2 with GH gene deletion (age 11.2 (3.7-22.9) years; BA (GP) 8.2 years; height -6.5 +/- 1.6 SDS) were recruited for the multicenter study. At birth, length was more retarded (-1.38 SDS) than weight (-0.56 SDS). The rhIGF-I dose was 40-120 micrograms/kg BW twice daily s.c. In 26 patients, first year HV increased from 3.9 +/- 1.8 to 8.5 +/- 2.1 cm/year (delta (d) HT SDS 0.8 +/- 0.5). In 18 patients, second year HV was 6.4 +/- 2.2 cm/year (dHT SDS 0.4 +/- 0.5). There was normal progression of puberty. Mean progression of BA was 1.2 and 1.5 years/year during the first and second year. There was no dose effect of IGF-I on growth. Weight-for-height index (WHI) and skinfold thickness were significantly correlated at start, 12 and 24 months (r = 0.83, 0.87 and 0.79). Changes in WHI were positively correlated with dHT SDS during the first and second year (r = 0.54, 0.56). Serum IGF-I rose, IGF-II decreased, and IGFBP-3 remained constant. Adverse events were (number of occasions): headache (21) (early); hypoglycemia (13); papilloedema (1) (reversible); Bell's palsy (1) (reversible); lipohypertrophy (7) (late); tonsillectomy/adenoidectomy (3) (late). The results show that there is effective long-term treatment of GHIS with systemically administered IGF-I and support the view that IGFBPs play an important role in the action of IGF-I.

Adolescent↗