Immunoradiometric assay procedure a Isolation of specific antibodies b Preparation of labelled an... more Immunoradiometric assay procedure a Isolation of specific antibodies b Preparation of labelled antibodies c Assay procedure d Applications e Advantages Two-site assay a Method b Applications c Advantages Double-antibody immunoradiometric assay References The immunoradiometric assay (I) differs from conventional radioimmunoassay (RIA) systems (II) in that the compound to be measured is assayed directly by combination with specific labelled antibodies rather than in competition with a labelled derivative for a limited amount of antibody.
Nerve growth factor, like many other biologically active proteins, occurs in tissues and plasma a... more Nerve growth factor, like many other biologically active proteins, occurs in tissues and plasma at very low concentrations. The usual method for the assay of this protein is the bioassay originally described by Levi-Montalcini et al. (1954) with only minor modifications as described by several other workers (Cohen, 1960; Fenton, 1970; Varon et al., 1973). This assay consists of observing the fiber outgrowth elicited from explanted 8- to 10-day-old chick dorsal root ganglia by serially diluted NGF samples mixed into the culture medium. The concentrations required in this biological assay span the optimal range for the biological response; the amount of protein required for the maximal neurite outgrowth is taken as one biological unit. In the study of the mode of action of NGF, situations arise when the concentration of NGF to be detected is far below that required to obtain the maximal biological response, and so these levels cannot be determined accurately using the biological assay. Experiments designed to determine the source of NGF in the serum point out some of these problems. Here the submaxillary glands, one of the important normal sources of serum NGF, are removed and the decay in serum activity is followed. Other work using the biological assay showed that this procedure resulted in a decrease in NGF content in the serum to nonmeasurable levels (Caramia, et al., 1962).
Diminished taste acuity (hypogeusia) and zinc deficiency have been reported in children on mainte... more Diminished taste acuity (hypogeusia) and zinc deficiency have been reported in children on maintenance haemodialysis and with varying degrees of chronic renal failure. We have studied the effect of 6 weeks' zinc supplementation in 20 children with chronic renal impairment using a double-blind crossover trial. Although we achieved significant increases in serum zinc levels no significant improvement in taste acuity could be demonstrated. These studies provide no support for the belief that routine zine supplements are necessary in children with chronic renal failure.
Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 yea... more Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 years) whose heights and weights were between the third and 97th centiles. Urinary GH increased significantly with age, reaching a maximum in boys at 15-years-old and in girls at 13-years-old. Peak levels were five and three times higher in boys and girls respectively than in 4-year-olds. Maximum urinary GH excretion was seen at breast stages 3 and 4 in girls and at genital stage 4 in boys followed by a decline in both sexes at stage 5. Boys excreted more GH than girls during prepubertal and pubertal years. During prepubertal years there were fluctuations of urinary excretion of GH with age. Height, weight and pubertal status predicted 31% of the variability of urinary excretion of GH, and urinary excretion of creatinine, albumin and N-acetylglucosaminidase (NAG) predicted 52% of the variability. The importance of establishing sound age and sex-related reference ranges for urinary growth ho...
Twenty-eight children were treated for various cancers with protocols that included dichlorodiami... more Twenty-eight children were treated for various cancers with protocols that included dichlorodiamine platinum (cisplatin). Sixteen children were given intravenous magnesium after the administration of cisplatin, and 12 were given intravenous magnesium before and after administration of cisplatin. Serum magnesium concentration levels were monitored before, during, and after the full course of treatment and found to be lower in the first group of patients than in the second group. We recommend that magnesium supplements be given to patients receiving cisplatin during the precisplatin hydration period to prevent hypomagnesemia.
SUMMARY An immunoradiometric assay for parathyroid hormone has been developed. Antisera to bovine... more SUMMARY An immunoradiometric assay for parathyroid hormone has been developed. Antisera to bovine parathyroid hormone (BPTH) were screened for their ability to bind BPTH and human parathyroid hormone (HPTH). A BPTH-immunoadsorbent was used to extract antibodies from an antiserum which did not discriminate between BPTH and HPTH in a standard radioimmunoassay. These antibodies were labelled with 125I for use in the immunoradiometric assay. With this system as little as 5 pg BPTH and 8 pg HPTH could be detected. The serum concentration of BPTH was shown to rise in a cow rendered hypocalcaemic by an infusion of EDTA. Sera from patients with hyperparathyroidism contained high concentrations of hormone. These sera were found to dilute-out parallel to calibration curves obtained using HPTH extracted from parathyroid adenomata. The advantages of this method over the standard radioimmunoassay are discussed.
The possible mitogenic effects of a number of preparations of the myelin basic protein (MBP) of h... more The possible mitogenic effects of a number of preparations of the myelin basic protein (MBP) of human brain have been investigated in various cell types in culture, including human amniotic fluid cells. Intact human MBP, as well as fragments derived by BNPS-skatole and cathepsin D treatment, and isoelectric focusing fractions of human MBP, showed no mitogenic activity. These results are consistent with recent findings that the fibroblast growth factor (FGF) activity of bovine brain does not originate from MBP.
necessarily result in a doubling of the percentage of individuals with an IQ below 70. He conclud... more necessarily result in a doubling of the percentage of individuals with an IQ below 70. He concludes that this would result in 'a doubling of the number of mentally retarded children!'. This statement is true in the circular sense that there will be a doubling in the number of children with IQS below the semi-arbitary demarcation of 70, but i t is not necessarily true in any socially significant sense, such as doubling the number of persons requiring institutional care. Lest I be misunderstood again, my point is no! that minor decrements in IQ are trivial and can safely be ignored, but rather that the implications of isolated, small deficits in IQ are vague and ambiguous. I have recently outlined my position on this point4. An IQ deficit of five points may be very meaningful if taken in context of several other deficits, for example slower reaction time, decrements in auditory and speech processing, and increases in nonadaptive classroom behavior, as has been revealed by the Needleman 'group in their excellent study5. This and other recent research points to the compelling inference that asymptomatic lead exposure does have multiple and pervasive effects upon the neurocognitive functioning of children. In that context minor IQ differences are cause for serious concern.
We wished to evaluate the use of urinary GH measurements when compared to conventional GH provoca... more We wished to evaluate the use of urinary GH measurements when compared to conventional GH provocation tests in the assessment of short children. Children presenting for the first time to a regional growth clinic were assessed clinically by one observer. Investigations comprising standard GH provocation tests and measurement of urinary GH were undertaken to exclude GH deficiency. Fifty-eight children aged 5.8-16 years were enrolled. Ten were diagnosed on clinical assessment as GH deficient, 43 had delayed growth and/or familial short stature, and five had idiopathic short stature; the 48 children in the last two groups were defined as short normal. GH secretion was evaluated by two standard provocation tests and by the measurement of GH in five overnight urine collections. A normal peak GH concentration was defined as > 16 mU/l. The values for urinary GH excretion were compared to normal ranges (+/- 2 standard deviations from the mean), established in healthy schoolchildren of normal stature. All children considered GH deficient on clinical grounds had low peak GH concentrations on provocation tests, while 8/10 had low values of urinary GH excretion. All short normal children with normal peak GH concentrations (n = 36) on provocation tests and 11/12 children with low peak GH concentrations had urinary GH excretion within the normal range. There was therefore a significant difference in the classification of 'normal' GH secretion in the two tests. If the clinical diagnosis was used as the standard by which GH tests were judged, the predictive value of a positive urinary GH test in the diagnosis of GH deficiency was 89% compared with 45% for GH provocation tests.
We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on phy... more We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on physiological growth hormone secretion. We performed an analysis of 24-hour serum GH profiles using 20-minute sampling. Forty-four children were studied, of whom 21 were long-term survivors of acute lymphoblastic leukaemia and 23 were normal children. They were further subdivided into prepubertal, pubertal and post-pubertal groups. GH profiles were analysed by autocorrelation, Fourier transformation and spectral analysis of stationarized data, and peak detection using the Pulsar peak detection program. RESULTS In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups (62 (11-124) and 137 (142-158) IU/I/h respectively, (P less than 0.01)). There was also a change in the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post-pubertal groups but sharply focused in the pubertal group. In the cranially irradiated children there was no significant increase in AUC between the prepubertal (62(13-110) IU/I/h) and pubertal groups (92 (14-163) IU/I/h). The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranially irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty.
Conventional treatment of familial hypophosphaiaemic rickets with oral phosphate and 1 alpha-hydr... more Conventional treatment of familial hypophosphaiaemic rickets with oral phosphate and 1 alpha-hydroxycholecalciferol (1 alpha HCC) does not satisfactorily correct the metabolic or physical defects of the disease and can have adverse effects, such as nephrocalcinosis. Hyperoxaluria from increased oral phosphate intake may contribute to nephrocalcinosis. Growth hormone enhances renal tubular phosphate reabsorption and 1,25-dihydroxy-cholecalciferol production in normal and in GH deficient individuals, and may thus be of benefit to patients with familial hypophosphataemic rickets. We have assessed the acute effects of GH on phosphate and calcium metabolism in 6 children (age 4-14 years) with familial hypophosphataemic rickets. Each patient served as his/her own control and received the following in a sequential non-randomized design: conventional treatment with oral phosphate 1.0-3.4 mmol/kg/day in 3-6 divided doses and 1 alpha HCC 18-31 ng/kg/day-no treatment-GH 0.05 mg/kg daily-GH and 1 alpha HCC-and GH with phosphate and 1 alpha HCC. Each treatment was given for 7 days with 7 day periods of no treatment in between. Glomerular filtration rate, tubular maximum rate of phosphate reabsorption per litre of glomerular filtrate (TmP/GFR) and serum 1,25-dihydroxycholecalciferol increased with GH. Mean 24-hour plasma phosphate concentrations did not increase with GH but were higher in the treatment phases which included phosphate and 1 alpha HCC (P = 0.002). Serum PTH was higher when GH was given in combination with phosphate and 1 alpha HCC compared to other phases. Urine oxalate excretion did not differ between the treatment phases. GH seemed to partially correct the defects in renal tubular phosphate transport and 1 alpha-hydroxylation of 25-hydroxycholecalciferol. We speculate that the net effect of GH treatment was an increase in body phosphate, although this was not reflected in a change in plasma phosphate. Therefore, GH in combination with 1 alpha HCC may act as a phosphate sparing agent, permitting treatment with lower and less frequent doses of oral phosphate and reducing adverse effects such as nephrocalcinosis.
Thirteen boys with constitutional delay in growth and/or development aged 7-6 to 16 years receive... more Thirteen boys with constitutional delay in growth and/or development aged 7-6 to 16 years received 2.5mg/day of oxandrolone for 3 months. Their growth response on treatment and in the subsequent 3 months was compared to that of 14 age-matched untreated controls. Growth rates were analysed in groups arbitrarily defined by testicular volume at entry (< 4ml prepubertal, > 4ml pubertal). Growth velocities increased on oxandrolone (prepubertal, mean 4.4 to ?-5cm/year, P=.0.05: pubertal, mean 4-7 to 8cm/year,Pc 0-05). Over the next 3 months, the pubertal boys grew at 9*3cm/year, while the prepubertal group decelerated to 6.2cm/year. Both control groups showed no significant change in velocity over 6 months. GH responses to arginine and GRF, and to sleep in prepubertal boys, were unchanged throughout the study. However, in pubertal boys the mean GH levels ('area under the curve') during sleep at 3 and 6 months, had increased over baseline values, associated with a significant increase at 6 months in basal somatomedin-C (140 to 214ng/ml, P<O.O5). Oxandrolone does not alter the GH status of prepubertal boys, and thus probably promotes growth by a direct action at the growth plate. In contrast, the persistent growth acceleration of pubertal boys may be associated with increased GH and somatomedin-C levels: in this group, oxandrolone has proved a useful stimulus to growth. Boys with constitutional short stature and delayed puberty (CDGP) commonly present in the peripubertal period, with anxiety related to poor growth rather than retarded sexual maturation. The statural discrepancy from their peer group may contribute to psychological disturbance. For the severely distressed, there is a pressing need for active treatment with growth promoting agents. Over the last 15 years, the anabolic steroid, oxandrolone, has been available for clinical use to accelerate growth in those with short
We performe TSH dry-spot screening as “Central CH-Screening for SH” since 1980. It covers 99,3% o... more We performe TSH dry-spot screening as “Central CH-Screening for SH” since 1980. It covers 99,3% of all newborns in this area, the remaining are screened by more than 5 other laboratories. We follow up all cases of CH detected by our screening, either in our department or in collaboration with a local pediatrician. Since January 1980 we screened 95,657 out of 193,854 newborrsin this area. There were 879 recalls for serum with a declining recall rate from 2.23% in 1980 to 0.11% in 1987. Therapy and clinical follow-up was begun in 65 cases, of whom 30 were later considered transient hypothyroidism, 24 of them iodine-induced. Additional 4 children had transient, 2 so far permanent hypothyrotropinemia. The remaining 30 children are still under therapy (L-T4), therefore incidence of CH in our population is 1:3188. We saw seasonal variation in CH-incidence: 15 children were born between Jan. and April, 7 in Sept. and Oct. At about 2 years of age we reevaluate thyroid-function after disruption of T4 substitution, including scintigraphic scan, and intellectual and psychomotor developmental testing. Start of therapy in our patients was at day 6-33 (mean 13.3). Clinical follow-up of the children depicts insufficient L-Thyroxin substitution at one or more occasions in 80%. So far scintigraphic scan during follow-up showed 9 cases with athyreosis, 6 with ectopic thyroid tissue, and 3 with dyshormonogenesis. At age 2-4 mild deficiencies in intellectuel and psychomotor development could be demonstrated as a general trend in our patients, expressed as retardation in performance at or below the 90% level in a standardized testl. Severe retardation in 6 children (28%) as well as the milder forms was focussed on speech, perception, and less pronounced on fine motor abilities. Retardation showed no other correlation then with social status and severe additional illness.
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 1985
The analysis of serum albumin by bromocresol purple (BCP), by bromocresol green (BCG), and by ele... more The analysis of serum albumin by bromocresol purple (BCP), by bromocresol green (BCG), and by electroimmunoassay (EIA) has been compared in a mixed group of 100 hospital patients. Good agreement between the immunochemical and BCP methods, but a positive bias with the BCG method led to routine use of the BCP method. In a group of 19 paediatric patients on chronic haemodialysis the mean BCP-albumin was found to be lower than the true albumin, as determined by EIA, whereas the positive bias using the BCG method remained. The difference between BCP-albumin and EIA-albumin in the haemodialysis group varied from 0 to −;13 g/L (mean −7·1 g/L) but was effectively constant for most patients over a 3-month period. Possible mechanisms and necessary further investigations are discussed.
Immunoradiometric assay procedure a Isolation of specific antibodies b Preparation of labelled an... more Immunoradiometric assay procedure a Isolation of specific antibodies b Preparation of labelled antibodies c Assay procedure d Applications e Advantages Two-site assay a Method b Applications c Advantages Double-antibody immunoradiometric assay References The immunoradiometric assay (I) differs from conventional radioimmunoassay (RIA) systems (II) in that the compound to be measured is assayed directly by combination with specific labelled antibodies rather than in competition with a labelled derivative for a limited amount of antibody.
Nerve growth factor, like many other biologically active proteins, occurs in tissues and plasma a... more Nerve growth factor, like many other biologically active proteins, occurs in tissues and plasma at very low concentrations. The usual method for the assay of this protein is the bioassay originally described by Levi-Montalcini et al. (1954) with only minor modifications as described by several other workers (Cohen, 1960; Fenton, 1970; Varon et al., 1973). This assay consists of observing the fiber outgrowth elicited from explanted 8- to 10-day-old chick dorsal root ganglia by serially diluted NGF samples mixed into the culture medium. The concentrations required in this biological assay span the optimal range for the biological response; the amount of protein required for the maximal neurite outgrowth is taken as one biological unit. In the study of the mode of action of NGF, situations arise when the concentration of NGF to be detected is far below that required to obtain the maximal biological response, and so these levels cannot be determined accurately using the biological assay. Experiments designed to determine the source of NGF in the serum point out some of these problems. Here the submaxillary glands, one of the important normal sources of serum NGF, are removed and the decay in serum activity is followed. Other work using the biological assay showed that this procedure resulted in a decrease in NGF content in the serum to nonmeasurable levels (Caramia, et al., 1962).
Diminished taste acuity (hypogeusia) and zinc deficiency have been reported in children on mainte... more Diminished taste acuity (hypogeusia) and zinc deficiency have been reported in children on maintenance haemodialysis and with varying degrees of chronic renal failure. We have studied the effect of 6 weeks' zinc supplementation in 20 children with chronic renal impairment using a double-blind crossover trial. Although we achieved significant increases in serum zinc levels no significant improvement in taste acuity could be demonstrated. These studies provide no support for the belief that routine zine supplements are necessary in children with chronic renal failure.
Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 yea... more Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 years) whose heights and weights were between the third and 97th centiles. Urinary GH increased significantly with age, reaching a maximum in boys at 15-years-old and in girls at 13-years-old. Peak levels were five and three times higher in boys and girls respectively than in 4-year-olds. Maximum urinary GH excretion was seen at breast stages 3 and 4 in girls and at genital stage 4 in boys followed by a decline in both sexes at stage 5. Boys excreted more GH than girls during prepubertal and pubertal years. During prepubertal years there were fluctuations of urinary excretion of GH with age. Height, weight and pubertal status predicted 31% of the variability of urinary excretion of GH, and urinary excretion of creatinine, albumin and N-acetylglucosaminidase (NAG) predicted 52% of the variability. The importance of establishing sound age and sex-related reference ranges for urinary growth ho...
Twenty-eight children were treated for various cancers with protocols that included dichlorodiami... more Twenty-eight children were treated for various cancers with protocols that included dichlorodiamine platinum (cisplatin). Sixteen children were given intravenous magnesium after the administration of cisplatin, and 12 were given intravenous magnesium before and after administration of cisplatin. Serum magnesium concentration levels were monitored before, during, and after the full course of treatment and found to be lower in the first group of patients than in the second group. We recommend that magnesium supplements be given to patients receiving cisplatin during the precisplatin hydration period to prevent hypomagnesemia.
SUMMARY An immunoradiometric assay for parathyroid hormone has been developed. Antisera to bovine... more SUMMARY An immunoradiometric assay for parathyroid hormone has been developed. Antisera to bovine parathyroid hormone (BPTH) were screened for their ability to bind BPTH and human parathyroid hormone (HPTH). A BPTH-immunoadsorbent was used to extract antibodies from an antiserum which did not discriminate between BPTH and HPTH in a standard radioimmunoassay. These antibodies were labelled with 125I for use in the immunoradiometric assay. With this system as little as 5 pg BPTH and 8 pg HPTH could be detected. The serum concentration of BPTH was shown to rise in a cow rendered hypocalcaemic by an infusion of EDTA. Sera from patients with hyperparathyroidism contained high concentrations of hormone. These sera were found to dilute-out parallel to calibration curves obtained using HPTH extracted from parathyroid adenomata. The advantages of this method over the standard radioimmunoassay are discussed.
The possible mitogenic effects of a number of preparations of the myelin basic protein (MBP) of h... more The possible mitogenic effects of a number of preparations of the myelin basic protein (MBP) of human brain have been investigated in various cell types in culture, including human amniotic fluid cells. Intact human MBP, as well as fragments derived by BNPS-skatole and cathepsin D treatment, and isoelectric focusing fractions of human MBP, showed no mitogenic activity. These results are consistent with recent findings that the fibroblast growth factor (FGF) activity of bovine brain does not originate from MBP.
necessarily result in a doubling of the percentage of individuals with an IQ below 70. He conclud... more necessarily result in a doubling of the percentage of individuals with an IQ below 70. He concludes that this would result in &#39;a doubling of the number of mentally retarded children!&#39;. This statement is true in the circular sense that there will be a doubling in the number of children with IQS below the semi-arbitary demarcation of 70, but i t is not necessarily true in any socially significant sense, such as doubling the number of persons requiring institutional care. Lest I be misunderstood again, my point is no! that minor decrements in IQ are trivial and can safely be ignored, but rather that the implications of isolated, small deficits in IQ are vague and ambiguous. I have recently outlined my position on this point4. An IQ deficit of five points may be very meaningful if taken in context of several other deficits, for example slower reaction time, decrements in auditory and speech processing, and increases in nonadaptive classroom behavior, as has been revealed by the Needleman &#39;group in their excellent study5. This and other recent research points to the compelling inference that asymptomatic lead exposure does have multiple and pervasive effects upon the neurocognitive functioning of children. In that context minor IQ differences are cause for serious concern.
We wished to evaluate the use of urinary GH measurements when compared to conventional GH provoca... more We wished to evaluate the use of urinary GH measurements when compared to conventional GH provocation tests in the assessment of short children. Children presenting for the first time to a regional growth clinic were assessed clinically by one observer. Investigations comprising standard GH provocation tests and measurement of urinary GH were undertaken to exclude GH deficiency. Fifty-eight children aged 5.8-16 years were enrolled. Ten were diagnosed on clinical assessment as GH deficient, 43 had delayed growth and/or familial short stature, and five had idiopathic short stature; the 48 children in the last two groups were defined as short normal. GH secretion was evaluated by two standard provocation tests and by the measurement of GH in five overnight urine collections. A normal peak GH concentration was defined as &amp;amp;gt; 16 mU/l. The values for urinary GH excretion were compared to normal ranges (+/- 2 standard deviations from the mean), established in healthy schoolchildren of normal stature. All children considered GH deficient on clinical grounds had low peak GH concentrations on provocation tests, while 8/10 had low values of urinary GH excretion. All short normal children with normal peak GH concentrations (n = 36) on provocation tests and 11/12 children with low peak GH concentrations had urinary GH excretion within the normal range. There was therefore a significant difference in the classification of &amp;amp;#39;normal&amp;amp;#39; GH secretion in the two tests. If the clinical diagnosis was used as the standard by which GH tests were judged, the predictive value of a positive urinary GH test in the diagnosis of GH deficiency was 89% compared with 45% for GH provocation tests.
We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on phy... more We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on physiological growth hormone secretion. We performed an analysis of 24-hour serum GH profiles using 20-minute sampling. Forty-four children were studied, of whom 21 were long-term survivors of acute lymphoblastic leukaemia and 23 were normal children. They were further subdivided into prepubertal, pubertal and post-pubertal groups. GH profiles were analysed by autocorrelation, Fourier transformation and spectral analysis of stationarized data, and peak detection using the Pulsar peak detection program. RESULTS In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups (62 (11-124) and 137 (142-158) IU/I/h respectively, (P less than 0.01)). There was also a change in the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post-pubertal groups but sharply focused in the pubertal group. In the cranially irradiated children there was no significant increase in AUC between the prepubertal (62(13-110) IU/I/h) and pubertal groups (92 (14-163) IU/I/h). The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranially irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty.
Conventional treatment of familial hypophosphaiaemic rickets with oral phosphate and 1 alpha-hydr... more Conventional treatment of familial hypophosphaiaemic rickets with oral phosphate and 1 alpha-hydroxycholecalciferol (1 alpha HCC) does not satisfactorily correct the metabolic or physical defects of the disease and can have adverse effects, such as nephrocalcinosis. Hyperoxaluria from increased oral phosphate intake may contribute to nephrocalcinosis. Growth hormone enhances renal tubular phosphate reabsorption and 1,25-dihydroxy-cholecalciferol production in normal and in GH deficient individuals, and may thus be of benefit to patients with familial hypophosphataemic rickets. We have assessed the acute effects of GH on phosphate and calcium metabolism in 6 children (age 4-14 years) with familial hypophosphataemic rickets. Each patient served as his/her own control and received the following in a sequential non-randomized design: conventional treatment with oral phosphate 1.0-3.4 mmol/kg/day in 3-6 divided doses and 1 alpha HCC 18-31 ng/kg/day-no treatment-GH 0.05 mg/kg daily-GH and 1 alpha HCC-and GH with phosphate and 1 alpha HCC. Each treatment was given for 7 days with 7 day periods of no treatment in between. Glomerular filtration rate, tubular maximum rate of phosphate reabsorption per litre of glomerular filtrate (TmP/GFR) and serum 1,25-dihydroxycholecalciferol increased with GH. Mean 24-hour plasma phosphate concentrations did not increase with GH but were higher in the treatment phases which included phosphate and 1 alpha HCC (P = 0.002). Serum PTH was higher when GH was given in combination with phosphate and 1 alpha HCC compared to other phases. Urine oxalate excretion did not differ between the treatment phases. GH seemed to partially correct the defects in renal tubular phosphate transport and 1 alpha-hydroxylation of 25-hydroxycholecalciferol. We speculate that the net effect of GH treatment was an increase in body phosphate, although this was not reflected in a change in plasma phosphate. Therefore, GH in combination with 1 alpha HCC may act as a phosphate sparing agent, permitting treatment with lower and less frequent doses of oral phosphate and reducing adverse effects such as nephrocalcinosis.
Thirteen boys with constitutional delay in growth and/or development aged 7-6 to 16 years receive... more Thirteen boys with constitutional delay in growth and/or development aged 7-6 to 16 years received 2.5mg/day of oxandrolone for 3 months. Their growth response on treatment and in the subsequent 3 months was compared to that of 14 age-matched untreated controls. Growth rates were analysed in groups arbitrarily defined by testicular volume at entry (< 4ml prepubertal, > 4ml pubertal). Growth velocities increased on oxandrolone (prepubertal, mean 4.4 to ?-5cm/year, P=.0.05: pubertal, mean 4-7 to 8cm/year,Pc 0-05). Over the next 3 months, the pubertal boys grew at 9*3cm/year, while the prepubertal group decelerated to 6.2cm/year. Both control groups showed no significant change in velocity over 6 months. GH responses to arginine and GRF, and to sleep in prepubertal boys, were unchanged throughout the study. However, in pubertal boys the mean GH levels ('area under the curve') during sleep at 3 and 6 months, had increased over baseline values, associated with a significant increase at 6 months in basal somatomedin-C (140 to 214ng/ml, P<O.O5). Oxandrolone does not alter the GH status of prepubertal boys, and thus probably promotes growth by a direct action at the growth plate. In contrast, the persistent growth acceleration of pubertal boys may be associated with increased GH and somatomedin-C levels: in this group, oxandrolone has proved a useful stimulus to growth. Boys with constitutional short stature and delayed puberty (CDGP) commonly present in the peripubertal period, with anxiety related to poor growth rather than retarded sexual maturation. The statural discrepancy from their peer group may contribute to psychological disturbance. For the severely distressed, there is a pressing need for active treatment with growth promoting agents. Over the last 15 years, the anabolic steroid, oxandrolone, has been available for clinical use to accelerate growth in those with short
We performe TSH dry-spot screening as “Central CH-Screening for SH” since 1980. It covers 99,3% o... more We performe TSH dry-spot screening as “Central CH-Screening for SH” since 1980. It covers 99,3% of all newborns in this area, the remaining are screened by more than 5 other laboratories. We follow up all cases of CH detected by our screening, either in our department or in collaboration with a local pediatrician. Since January 1980 we screened 95,657 out of 193,854 newborrsin this area. There were 879 recalls for serum with a declining recall rate from 2.23% in 1980 to 0.11% in 1987. Therapy and clinical follow-up was begun in 65 cases, of whom 30 were later considered transient hypothyroidism, 24 of them iodine-induced. Additional 4 children had transient, 2 so far permanent hypothyrotropinemia. The remaining 30 children are still under therapy (L-T4), therefore incidence of CH in our population is 1:3188. We saw seasonal variation in CH-incidence: 15 children were born between Jan. and April, 7 in Sept. and Oct. At about 2 years of age we reevaluate thyroid-function after disruption of T4 substitution, including scintigraphic scan, and intellectual and psychomotor developmental testing. Start of therapy in our patients was at day 6-33 (mean 13.3). Clinical follow-up of the children depicts insufficient L-Thyroxin substitution at one or more occasions in 80%. So far scintigraphic scan during follow-up showed 9 cases with athyreosis, 6 with ectopic thyroid tissue, and 3 with dyshormonogenesis. At age 2-4 mild deficiencies in intellectuel and psychomotor development could be demonstrated as a general trend in our patients, expressed as retardation in performance at or below the 90% level in a standardized testl. Severe retardation in 6 children (28%) as well as the milder forms was focussed on speech, perception, and less pronounced on fine motor abilities. Retardation showed no other correlation then with social status and severe additional illness.
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 1985
The analysis of serum albumin by bromocresol purple (BCP), by bromocresol green (BCG), and by ele... more The analysis of serum albumin by bromocresol purple (BCP), by bromocresol green (BCG), and by electroimmunoassay (EIA) has been compared in a mixed group of 100 hospital patients. Good agreement between the immunochemical and BCP methods, but a positive bias with the BCG method led to routine use of the BCP method. In a group of 19 paediatric patients on chronic haemodialysis the mean BCP-albumin was found to be lower than the true albumin, as determined by EIA, whereas the positive bias using the BCG method remained. The difference between BCP-albumin and EIA-albumin in the haemodialysis group varied from 0 to −;13 g/L (mean −7·1 g/L) but was effectively constant for most patients over a 3-month period. Possible mechanisms and necessary further investigations are discussed.
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