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Biomedical subjects

H Maxwell

Publications and source records attributed to H Maxwell.

At least 19 recordsLinked to original sources
PubMed2001

Use of rapamycin in a transplant patient who developed cyclosporin neurotoxicity.

We describe the case of a paediatric kidney transplant patient who developed cyclosporin neurotoxicity on day 7 post-transplant. Consequently, her cyclosporin was stopped and she was commenced on rapamycin. Over the next 3 weeks her creatinine remained elevated and she had several episodes of biopsy proven rejection, despite increasing the initial dose of rapamycin by tenfold. Her whole blood rapamycin levels also remained well below the target range of 10-20 ng/ml. On day 38 post-transplant, the decision was made to add tacrolimus to her immunosuppression. At the same time, phenytoin, which had been commenced during her episode of cyclosporin neurotoxicity, was withdrawn. After this point her rapamycin blood levels rapidly increased to within the therapeutic range and she improved clinically. We propose that phenytoin, as a p450 cytochrome enzyme inducer, increased the metabolism of rapamycin in this patient and hence decreased the initial therapeutic effectiveness of this drug.

Anticonvulsants↗
PubMed2000

Growth hormone and markers of immune function in children with renal transplants.

Lymphocyte subsets and T cell activation markers were measured in ten children with renal transplants for up to 1 year before and during their 1st year of recombinant human growth hormone (rhGH) treatment. The number of lymphocytes, helper or cytotoxic T cells or natural killer cells, and the T cell expression of CD25, CD26 and HLA-DR antigens were not altered by rhGH. B cell numbers declined both before and during treatment. There was no difference in lymphocyte subset numbers between children with and without rejection episodes.

Adolescent↗
PubMed1998

Catch-up growth occurs after renal transplantation in children of pubertal age.

OBJECTIVE: Assessment of growth after renal transplantation in children of pubertal age by analyzing the annual increment in height standard deviation score (Ht SDS) in all girls > or =10 years and boys > or =11 years of age at the time of transplantation until latest follow-up (minimum 2 years). PATIENTS: A total of 59 grafts were placed in 54 recipients (30 boys) between December 1984 and January 1995. Mean (range) age at transplantation was 13.6 years (10.1 to 17.7 years). Fifty-one percent had congenital renal disease, 36% acquired renal disease, and 13% had hereditary nephropathies. Eighty-seven percent were first grafts; of these, 29% were performed pre-emptively, and 23% were from living related donors. RESULTS: Mean (SD) Ht SDS at transplantation was -1.8 (0.2) and increased significantly thereafter, such that it was -1.6 (0.2) at 1 year, n = 52; -1.5 (0.2) at 2 years, n = 47; -1.0 (0.2) at 3 years, n = 27; -0.7 (0.3) at 4 years, n = 19; and -0.6 (0.3), n = 13, at 5 years after transplantation (analysis of variance, P < .001). The greatest improvement in Ht SDS in the first year was seen in children with the highest glomerular filtration rate (r = 0.429, P = .002) and in those who were shortest at the time of transplantation (r = -0.356, P = .009). CONCLUSION: Catch-up growth occurs in children receiving renal transplants during the expected time of puberty.

Adolescent↗
PubMed1998

Randomised controlled trial of recombinant human growth hormone in prepubertal and pubertal renal transplant recipients. British Association for Pediatric Nephrology.

AIMS: To evaluate the efficacy (height velocity (HV), change in height standard deviation score (delta HSDS)), and safety (glomerular filtration rate (GFR), incidence of rejection, and calcium and glucose metabolism) of recombinant human growth hormone (rhGH) treatment after renal transplantation. DESIGN: A two year randomised controlled trial. SUBJECTS: Fifteen prepubertal and seven pubertal children: mean (SD) age, 13.0 (2.6) and 15.2 (2.4) years, respectively; mean (SD) GFR, 51 (30) and 48 (17) ml/min/1.73 m2, respectively. Six prepubertal and three pubertal children were controls during the first year; all received rhGH in the second year. RESULTS: In the first year, mean (SE) HV and delta HSDS in the prepubertal treated group increased compared with controls: 8.1 (0.9) v 3.7 (0.6) cm/year and 0.6 (0.1) v -0.3 (0.2), respectively. In the pubertal treated group, mean (SE) HV and delta HSDS were also greater: 10.1 (0.6) v 3.9 (1.3) cm/year and 0.6 (0.1) v -0.1 (0.2), respectively. Comparing all treated and control children, there was no significant change in GFR: treated group, mean (SE) 9.9 (5.4) ml/min/1.73 m2 v control group, -1.6 (7.6) ml/min/1.73 m2. There were also no differences in the incidence of rejection in the first year: eight episodes in 13 patients v five episodes in nine patients, respectively. Phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and fasting insulin concentrations rose during the first year of treatment, but not thereafter. In the second year of treatment, HV remained above baseline. CONCLUSION: Treatment with rhGH improves growth in prepubertal and pubertal children with renal transplants, with no significant change in GFR or the incidence of rejection. Phosphate, ALP, PTH, and insulin increased during the first year of treatment.

Adolescent↗
PubMed1996

Factors influencing the response to growth hormone in children with renal disease.

The effects of age, height velocity over the preceding year, glomerular filtration rate (GFR) and prednisolone dose on growth response have been assessed by single and multiple linear regression analysis in 23 prepubertal children [age, mean (SD), 8.2 (2.5) years] with chronic renal failure (CRF) and 16 prepubertal children [12.1 (2.3) years] with renal transplants treated for 1 year with recombinant human growth hormone (rhGH), 30 U/m2 per week. Height velocity [mean (SD), cm/year] increased from 4.7 (1.3) to 9.7 (2.1) (P < 0.0001) in the CRF group and 3.1 (1.6) to 7.3 (2.8) (P < 0.0001) in the transplant group. In the CRF group, there was a correlation between age and height velocity, both in the pretreatment year (r = -0.755, P < 0.0001) and during treatment (r = -0.421, P = 0.045). There was no correlation between pretreatment height velocity or GFR and response to rhGH. In the transplanted children height velocity during the treatment year correlated with age (r = -0.647, P = 0.007), prednisolone dose (r = -0.689, P = 0.003), GFR (r = 0.542, P = 0.030) and pretreatment height velocity (r = 0.655, P = 0.006). Multiple regression analysis showed prednisolone dose and age to be the most important predictors of response.

Anti-Inflammatory Agents↗
PubMed1996

Effects of recombinant human growth hormone on renal function in children with renal transplants.

OBJECTIVE: To provide accurate measurement of renal function during treatment with recombinant human growth hormone (rhGH). METHODS: We measured glomerular filtration rate and effective renal plasma flow by clearance of inulin and para-aminohippuric acid before rhGH therapy, after 1 week, and then at 6-month intervals for up to 2 years of treatment in 16 children (mean (SD) age = 13.1 (2.2) years; glomerular filtration rate = 52 (27) ml/min per 1.73 m2). The mean (SD) time from transplantation was 6.5 (3.6) years. RESULTS: Linear growth velocity during rhGH therapy increased from 4.0 (1.8) to 8.8 (2.6) cm/yr (p < 0.0001). One child was withdrawn after 9 months because of abnormal glucose tolerance, and another child received a second renal transplant after 18 months. Glomerular filtration rate increased to 57 (29) ml/min per 1.73 m2 at 1 week (p = 0.004), remained improved at 6 months (63 (30); p = 0.013), but was not significantly better at 1 year (59 (33)). Effective renal plasma flow on day 1 was 237 (127) ml/min per 1.73 m2 and was unchanged on day 8 (244 (123)), at 6 months (271 (149)), and after 1 year (269 (157)). During the study there was no significant change in filtration fraction, blood pressure, or kidney volume, and excretion of microalbumin and N-acetylglucosaminidase was unaltered. There was one rejection episode per 14.8 patient-months in the year before treatment, 1 per 18.9 patient-months during the first year of treatment, and 1 per 13 patient-months during the second year of rhGH therapy. CONCLUSION: Treatment with rhGH improves growth in children with renal transplants. Glomerular filtration rate was increased after 1 week and 6 months of rhGH therapy but returned to baseline values thereafter. The data indicate the need for long-term follow-up of children with renal transplants who are receiving rhGH.

Adolescent↗
PubMed1996

Recombinant human growth hormone treatment in infants with chronic renal failure.

Poor growth is a particular problem for children with congenital renal disease. A one year trial of the use of recombinant human growth hormone (rhGH) in eight infants and young children with chronic renal failure is reported here. At entry bone age was less than 2 years, mean (range) chronological age 1.9 (1.3-2.7) years, and glomerular filtration rate (GFR) was 17 (9-42) ml/min/1.73 m2. Height standard deviation score (SDS) was -3.3 (-4.6 to -2.0) and height velocity SDS was -1.3 (-3.1 to 0.7). One child was withdrawn when he received a renal transplant after 9.5 months. Two children required dialysis, but remained in the trial. Treatment with rhGH resulted in an increase in height SDS to -2.2 (-4.2 to -0.9), p = 0.0002, and height velocity SDS to 1.1 (-0.7 to 2.6), p = 0.006. There was no change in GFR and no serious adverse events. There was no effect on plasma lipids, calcium, phosphate, intact parathyroid hormone, or glucose. Alkaline phosphatase rose significantly. Thus rhGH improved growth in eight infants with chronic renal failure, with four children entering the normal range.

Body Height↗
PubMed1996

The hypothalamo-pituitary-growth hormone insulin-like growth factor 1 axis in children with chronic renal failure.

Growth hormone (GH) levels are high in children with chronic renal failure (CRF), and there is increased hypothalamic sensitivity to the factors that normally modulate GH secretion. GH binding protein (GHBP) is decreased, which may reflect decreased GH receptor activity. IGFBP3 levels are normal in both CRF and transplanted children when measured by immunoradiometric assay, but intact IGFBP3 is low in transplanted children with an excess of small fragments, measured by Western immunoblotting. These fragments may interfere with IGF1 bioactivity.

Aging↗
PubMed1995

Differential effects of recombinant human growth hormone on glomerular filtration rate and renal plasma flow in chronic renal failure.

In normal subjects recombinant human growth hormone (rhGH) increases glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) through the action of insulin-like growth factor-I (IGF-I). We have measured clearance of inulin and para-aminohippuric acid in 18 children with chronic renal failure (CRF) during their 1st year of rhGH treatment to look at the immediate (first 3 h), short-term (1 week) and long-term (1 year) effects of treatment. On day 1 mean (range) age was 9.1 (4.9-13.9) years, GFR 19 (9-58) and ERPF 77 (34-271) ml/min per 1.73 m2. During treatment height velocity increased from 4.5 (1.7-6.5) to 9.5 (4.8-12.7) cm/year (P < 0.0001). Two children required dialysis after 0.75 years and 1 child was electively transplanted after 0.5 years. There were no other serious adverse events. GFR and ERPF were unchanged in the 3 h following rhGH. GFR remained constant on day 8, 22 (6-56) and after 1 year, 20 (9-59) ml/min per 1.73 m2. ERPF increased to 96 (33-276) ml/min per 1.73 m2 on day 8 (P = 0.005), and remained elevated, but not significantly so, at 99 (24-428) ml/min per 1.73 m2 at 1 year. Fasting IGF-I increased from 147 (46-315) ng/ml to 291 (61-673) by day 8 (P < 0.003), and to 341 (101-786) ng/ml at 1 year. There was no correlation between the change in IGF-I and renal function. Blood pressure, albumin excretion and dietary protein intake were unchanged by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Correlation between pulmonary cytochrome P450 transcripts and the organ-selective pneumotoxicity of 3-methylindole.

3-Methylindole (3MI) is a species- and organ-selective pneumotoxin; goats are the most susceptible species, mice are intermediate in susceptibility, and rabbits are the least susceptible species to its toxicity. Four different cDNA probes representative of human cytochrome P450 genes CYP2F1, CYP4B1, CYP2A6, and CYP2B6 were hybridized against RNA from lung and liver tissues of goat, mouse and rabbit. Transcripts representative of pulmonary P450s CYP2F1, CYP4B1 and CYP2B6 were present in goat lung. Transcripts for the CYP2F1 and CYP4B1 genes were observed in rabbit and mouse lung. In general, the probes selectively hybridized to pulmonary but not hepatic transcripts of all three species. The differences in susceptibilities among the three species could not be explained by the lack of 4B1 and 2F1 transcripts in the lungs of mice or rabbits that are less susceptible than goats, but the selective expression in the lung tissues of all three species may participate in the organ-selective bioactivation and pulmonary toxicity of 3MI in these species.

Animals↗