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Biomedical subjects

L Rees

Publications and source records attributed to L Rees.

At least 55 records · Page 3Linked to original sources
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 One child was withdrawn after 9 months because of abnormal glucose tolerance, and another child received a second renal transplant after 18 months.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

A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1).

Autosomal dominant polycystic kidney disease (ADPKD) is the most common single gene disorder resulting in renal failure. It is generally an adult onset disease, but rarely, cases of severe childhood polycystic disease arise in ADPKD families. The clear clinical anticipation in these pedigrees has led to the suggestion that the mutation may be an unstable trinucleotide repeat. We have now identified a nonsense mutation, Tyr3818Stop, in one such family (P117) within the major ADPKD gene, polycystic kidney disease 1 (PKD1). The mutation is shown to be a de novo change in the father, and of grandpaternal origin. PKD1 manifests as typical adult onset disease in the father, but is seen as severe disease, detected as enlarged polycystic kidneys in utero, in one of a pair of dizygotic twins; the other twin has the mutation but no evidence of cysts, consistent with an adult onset disease course. The finding of the same stable mutation associated with very different disease severity in this family indicates that phenotypic variation in PKD1 is not due to a dynamic mutation. It seems most likely that a small number of modifying factors may radically affect the course of disease in PKD1; identification of such factors will have important prognostic implications in this disorder.

Adult↗
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↗
PubMed1996

The role of recombinant human growth hormone (rhGH) in pubertal patients.

Growth response to rhGH decreases with increasing age. Transplanted adolescents, however, respond to rhGH in a comparable way to that of younger children. Caution should be used in transplanted children who, in our experience, grow as well as younger children. Whether or not the use of rhGH improves final height if used during puberty remains unknown.

Adolescent↗
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↗
PubMed1993

Undergraduate medical education.

Pressures from students and teachers, from professional bodies, and from changes in the way health care is delivered are all forcing a rethink of how medical students should be taught. These pressures may be more intense in London but are not confined to it. The recommendation the Tomlinson report advocates that has been generally welcomed is for more investment in primary care in London. General practitioners have much to teach medical schools about effective ways of learning, but incentives for teaching students in general practice are currently low, organising such teaching is difficult and needs resources, and resistance within traditional medical school hierarchies needs to be overcome. Likewise, students value learning within local communities, but the effort demanded of public health departments and community organisations is great at a time when they are under greater pressure than ever before. The arguments over research that favour concentration in four multifaculty schools are less clear cut for undergraduate education, where personal support for students is important. An immediate concern is that the effort demanded for reorganising along the lines suggested by Tomlinson will not leave medical schools much energy for innovating.

Community Medicine↗
PubMed1993

Prospective cytomegalovirus surveillance in paediatric renal transplant patients.

Fifty-eight consecutive paediatric recipients of 65 renal transplants were prospectively studied for up to 72 months for evidence of cytomegalovirus (CMV) infection. Blood, urine and saliva were screened for CMV pre transplant and then weekly for the first 6 weeks, and monthly thereafter, by conventional cell culture and by detection of early antigen fluorescent foci. Donor CMV serostatus was available in 51 cases. All patients received triple therapy as immunosuppression and none had CMV prophylaxis. Twenty-six episodes of CMV infection (40% of transplants) and 10 of CMV disease (15%) were identified. Donor CMV seropositivity, regardless of recipient CMV serostatus, was significantly associated with CMV infection (P = 0.04). First CMV excretion was significantly earlier in patients who subsequently became symptomatic than in those who did not (P = 0.04), and a positive blood culture was significantly associated with CMV disease (P = 0.04). We found no association between extra anti-rejection treatment or recipient's age and CMV infection or disease. CMV disease had no influence on renal function as assessed by glomerular filtration rate at 6, 12 and 24 months post transplant, nor on graft loss. CMV disease was fatal in 1 patient. We conclude that trials of CMV prophylactic agents are indicated, particularly in recipients of CMV seropositive grafts. A positive blood culture should lead to consideration of anti-CMV therapy.

Adolescent↗
PubMed1992

Plasma atrial natriuretic peptide and renin-aldosterone in patients with cirrhosis and ascites: basal levels, changes during daily activity and nocturnal diuresis.

Measurements of plasma atrial natriuretic peptide concentrations at 8 AM showed raised levels in 21 patients with cirrhosis and ascites (10.5 +/- 0.8 pmol/L) compared with levels in 10 age-matched controls (4.1 +/- 0.64 pmol/L; p less than 0.0001). In eight patients and 10 controls, atrial natriuretic peptide, plasma renin activity, plasma aldosterone and urinary sodium excretion were measured every 4 hr for 24 hr. Subjects were mobile between 8 AM and 11 PM and supine from 11 PM to 8 AM. In controls, urinary sodium excretion was highest between 4 PM and 11 PM (19.34 +/- 3.74 mumol/min) and lowest between midnight and 8 AM (7.06 +/- 1.23 mumol/min; p less than 0.001). In patients, urinary sodium excretion was 0.63 +/- 0.14 mumol/min between 4 PM and midnight and 1.85 +/- 0.71 mumol/min (p less than 0.08) between midnight and 8 AM. In patients during the day, mean plasma atrial natriuretic peptide concentration did not change despite large individual variation, but large, sustained rises in plasma renin activity and plasma aldosterone were seen. Correlations were noted between atrial natriuretic peptide and urinary sodium excretion between midnight and 8 AM (r = 0.65; p less than 0.02) and 4 PM and midnight (r = 0.54; p less than 0.05) but not between 8 AM and 4 PM. Plasma renin activity dropped from 12.54 +/- 2.49 at midnight to 7.41 +/- 0.88 pmol/hr/ml at 8 AM (p less than 0.05); plasma aldosterone decreased from 1,032 +/- 101 to 798 +/- 56 pmol/L (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Regeneration of axons in the optic nerve of the adult Browman-Wyse (BW) mutant rat.

We have studied the regeneration of axons in the optic nerves of the BW rat in which both oligodendrocytes and CNS myelin are absent from a variable length of the proximal (retinal) end of the nerve. In the optic nerves of some of these animals, Schwann cells are present. Axons failed to regenerate in the exclusively astrocytic environment of the unmyelinated segment of BW optic nerves but readily regrew in the presence of Schwann cells even across the junctional zone and into the myelin debris filled distal segment. In the latter animals, the essential condition for regeneration was that the lesion was sited in a region of the nerve in which Schwann cells were resident. Regenerating fibres appeared to be sequestered within Schwann cell tubes although fibres traversed the neuropil intervening between the ends of discontinuous bundles of Schwann cell tubes, in both the proximal unmyelinated and myelin debris laden distal segments of the BW optic nerve. Regenerating axons never grew beyond the distal point of termination of the tubes. These observations demonstrate that central myelin is not an absolute requirement for regenerative failure, and that important contributing factors might include inhibition of astrocytes and/or absence of trophic factors. Regeneration presumably occurs in the BW optic nerve because trophic molecules are provided by resident Schwann cells, even in the presence of central myelin, oligodendrocytes and astrocytes. All the above experimental BW animals also have Schwann cells in their retinae which myelinate retinal ganglion cell axons in the fibre layer. Control animals comprised normal Long Evans Hooded rats, BW rats in which both retina and optic nerve were normal, and BW rats with Schwann cells in the retina but with normal, i.e. CNS myelinated, optic nerves. Regeneration was not observed in any of the control groups, demonstrating that, although the presence of Schwann cells in the retina may enhance the survival of retinal ganglion cells after crush, concomitant regrowth of axons cut in the optic nerve does not take place.

Animals↗
PubMed1992

Microcephaly, focal segmental glomerulonephritis and marfanoid habitus in two sibs.

Two female sibs aged 15 and 18 years with microcephaly, mental retardation and marfanoid habitus who developed focal segmental glomerulonephritis leading to renal failure are described. This combination of features appears to represent a unique syndrome distinct from previous reports of microcephaly in association with the nephrotic syndrome. The mode of inheritance is likely to be autosomal recessive.

Adolescent↗
PubMed1991

Effect of tetrahydroaminoacridine on cognition, function and behaviour in Alzheimer's disease.

OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer's disease. DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice in a community hospital. PATIENTS: Thirty-four patients with moderate to severe Alzheimer's disease. Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose. For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour. The results for individual patients showed no subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important benefits in Alzheimer's disease and is associated with appreciable toxic effects.

Activities of Daily Living↗
PubMed1991

The influence of steroid therapy and recombinant human erythropoietin on the growth of children with renal disease.

Long-term steroid therapy has a depressant effect on hypothalamo-pituitary pulsatile secretion of growth hormone (GH), and this results in an attenuated pubertal growth spurt. Oxandrolone and recombinant human GH improve growth rates in children taking long-term steroid therapy for renal disease, but there are potential side effects. Treatment with recombinant human erythropoietin improved the growth of three prepubertal, but not three pubertal haemodialysis patients.

Adolescent↗
PubMed1991

Clinical significance of primitive reflexes in Alzheimer's disease.

STUDY OBJECTIVE: To establish the relationship between cognition, behavior, function, and clinical characteristics on the one hand, and the presence of primitive reflexes (PR) (pout, snout, palmomental and grasp) in patients with Alzheimer's disease (AD). DESIGN: Cross-sectional survey. SETTING: Secondary care geriatric practice specializing in the assessment of cognitive impairment. SUBJECTS: 136 consecutive patients presenting with AD. MEASUREMENTS: PR were assessed in standardized fashion by a single clinician. Cognitive function was measured using the Standardized Mini-Mental Status Examination, activities of daily living (ADL) and instrumental activities of daily living (IADL) were measured using the Lawton scale, and behavior was measured using the Behavioural Problem Checklist. RESULTS: There was no difference in age or duration of dementia in those with and without PR, nor was there any difference in cognitive function. Despite this, patients with PR showed a greater degree of functional limitation and dysfunctional behavior. There was also a higher incidence of rigidity, gait abnormalities, and apraxia in patients with PR. CONCLUSIONS: Patients with primitive reflexes had more severe impairment in ADL function and dysfunctional behavior for an equal level of cognitive function.

Activities of Daily Living↗