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Biomedical subjects

J Perheentupa

Publications and source records attributed to J Perheentupa.

At least 127 records · Page 7Linked to original sources

Disturbed calcium and phosphate homeostasis during treatment with ACTH of infantile spasms.

Kidney histology of five infants who died during or immediately after treatment with adrenocorticotrophic hormone (ACTH) showed severe tubular and interstitial calcinosis. We therefore studied serum concentrations of calcium, inorganic phosphate, and parathormone, serum activities of alkaline phosphatase, and urinary excretion of calcium, inorganic phosphate, and cyclic adenosine monophosphate (cAMP) in 16 other children with infantile spasms before, during, and after 6 weeks of treatment with ACTH. During the treatment the following observations were made: hypocalcaemia developed in three infants; the mean daily urinary excretion of calcium in the group increased threefold and seven infants had hypercalciuria; the excretion of phosphate increased but its tubular reabsorption remained stable; and in most infants serum parathormone and urinary cAMP excretion increased, and in four infants they increased to supranormal concentrations. These biochemical changes were reversible in most infants. Radiographs suggested loss of bone mass by 3-4 weeks of treatment, with rapid recovery after treatment. We conclude that infants treated with ACTH for infantile spasms are at risk of suffering disturbance in calcium and phosphate homeostasis, which leads to nephrocalcinosis.

Adrenocorticotropic Hormone↗

Adrenocortical hyporesponsiveness after treatment with ACTH of infantile spasms.

The hypothalamic-pituitary-adrenocortical axis was studied in 10 infants before and during a six week period of treatment with adrenocorticotrophic hormone (ACTH) and three days and one and two weeks after its stopping. During the treatment 24 hour urinary cortisol excretion increased 20 to 350-fold (mean 100) above the basal value. Mean morning serum cortisol concentration, measured 24 hours after the preceding ACTH dose, did not increase. After the treatment mean urinary cortisol excretion was subnormal and mean morning serum cortisol concentration was below the pretreatment value. The mean serum cortisol response to a vasopressin test was reduced and shortened throughout the post-treatment observation period. The mean serum cortisol response to an intravenous ACTH test was not significantly different from the pretreatment response three days after treatment but was clearly reduced thereafter. At one and two weeks after treatment the basal concentrations of serum cortisol of one third of the patients and the post-ACTH concentrations of two thirds were subnormal. We conclude that in infants treatment with ACTH may cause adrenocortical hyporesponsiveness.

Adrenocorticotropic Hormone↗

Neonatal hyperthyroidism in mice has different effects on epidermal growth factor levels in submandibular gland, urine, and blood.

We examined long-term effects of neonatal hyperthyroidism in female mice by measuring the epidermal growth factor levels in the submandibular gland, urine, and serum at the age of 31 days. Hyperthyroxinemia was induced by thyroxine injections (0.4 microgram/g/day) on days 0-6. Littermate controls received the alkaline saline vehicle. The treatment accelerated incisor eruption and eyelid opening. It also retarded growth. The elevation of plasma thyroxine concentration which normally occurs during wk 2 to reach a peak around day 15 was abolished. Submandibular gland epidermal growth factor levels on day 31 were markedly subnormal, indicating maturational delay. In contrast, epidermal growth factor levels were unaffected in urine and supranormal in serum. These differences in response suggest that the regulatory mechanisms governing epidermal growth factor levels in tissues and fluids may acquire thyroid hormone dependence at different stages.

Animals↗

Transient increase in postnatal testicular activity is not revealed by longitudinal measurements of salivary testosterone.

Testicular steroidogenic activity in 22 boys was monitored longitudinally over the first 6 months of life using salivary T measurements. Samples were collected biweekly. The highest T levels, 130 +/- 12 pmol/liter (mean +/- SE, n = 22), were observed on days 2-10. The values then gradually declined to a mean of about 30 pmol/liter after month 4. No secondary peak in salivary T appeared, in contrast to the 1-3 month peak in serum T previously reported. The overall levels of T, reflected by the areas under the T concentration curves over the whole period, varied by a factor of three among the subjects studied. It is concluded that postnatal testicular activity may have its most marked physiologic effects immediately after birth rather than at the time of the 1-3-month peak of serum T. Furthermore, the overall exposure to androgen is individually greatly variable.

Age Factors↗

Subnormal concentrations of urinary epidermal growth factor in patients with kidney disease.

We determined the concentrations of immunoreactive epidermal growth factor (irEGF) and creatinine in urine samples from 47 adult patients with various kidney diseases and wide ranges of azotemia and proteinuria. In most of the patients, urinary irEGF concentrations (nanograms per mg creatinine) were markedly subnormal. In the entire group, urinary irEGF correlated with creatinine clearance (r = 0.79; P less than 0.001) and serum creatinine concentration (r = -0.85; P less than 0.001). In the subgroups of patients with primarily glomerular or tubulointerstitial diseases, similar correlations were found. By contrast, there was no correlation with proteinuria. We also determined the concentrations of plasma irEGF in five patients with azotemia. In four patients, the irEGF to creatinine concentration ratio was 1.9- to 8.9-fold higher in urine than in plasma, indicating that plasma irEGF was not the main source of urinary irEGF in these patients. Our data are compatible with the theory that urinary irEGF originates from nephrons per se.

Adolescent↗

Reduced urinary epidermal growth factor levels in Snell dwarf mutant mice.

Because of findings implicating thyroid and growth hormones in the regulation of urinary EGF concentration, we determined urine and kidney EGF concentrations and relative kidney weights in both sexes of 8 weeks old dwarf mutant mice of the Snell strain and their normal littermates. Both male and female dwarfs had subnormal urine and kidney EGF concentrations. A female greater than male sex difference in both concentrations was present in the normal mice, but not in the dwarfs. The male greater than female sex difference in relative kidney weight, which has been demonstrated in normal mice of the Swiss-Webster strain, was not present in the normal or dwarf Snell mice.

Aging↗

Patients with acromegaly come from tall families.

The heights of 59 patients with acromegaly and their first-degree relatives were studied. The mean height SD score (SDS) for the patients was 0.93 +/- 1.19 (equivalent to 5.6 cm above the population mean), and for their siblings (N = 166) 0.39 +/- 1.05 (2.3 cm above the population mean) (P less than 10-5 for difference from the general population). The height distribution of both groups was markedly positively skewed. Probably the parents were as tall (in relation to the population of their age) as the siblings. Growth data were available for 13 of the patients and showed that the height of the tall (SDS greater than 2.0) patients had increased by 2.5-10 (mean 5) cm after normal cessation of growth. This explains the extra height of the patients over their siblings. Only 2 of the 13 patients became oversized for their families during the normal growth period. We suggest that in a part of the population with acromegaly the disease is associated with primary genetic tallness.

Acromegaly↗

Supplementation with human milk protein improves growth of small premature infants fed human milk.

We investigated the influence of human milk protein and medium-chain triglyceride supplementations of human milk feedings on the growth of very low birth weight infants during their first weeks of life. A group of 44 preterm infants with birth weights of less than 1,520 g and a mean gestational age of 30.3 weeks was randomly divided into four groups to receive plain human milk or human milk supplemented with human milk protein (0.9 g/dL), with medium-chain triglycerides (1 g/dL), or with both. The medium-chain triglyceride oil supplementation did not influence the growth of these infants. The infants given supplementary protein gained weight faster during weeks 4 to 6 than those without (18.5 +/- 0.7 v 15.1 +/- 0.6 g/kg/d; mean +/- SEM; P = .001). After 4 weeks of age the infants given supplementary protein had a mean weight gain equal to the mean intrauterine rate, in contrast to the infants of the other groups, who grew more slowly until age 6 weeks. Furthermore, we found a correlation between serum albumin concentration and weight gain during the seventh week of life (P = .018). The length growth velocity for the infants with protein supplementation was 0.99 +/- 0.06 cm/wk (mean +/- SEM) and for those without 0.83 +/- 0.05 cm/wk (P = .043). There was no difference in growth of head circumference between the groups. We conclude that human milk protein supplementation improves the growth of small premature infants fed human milk, and that the protein concentration of bank milk is insufficient for their adequate growth.

Female↗

GnRH and HCG tests are both necessary in differential diagnosis of male delayed puberty.

The discriminative power of the gonadotropin releasing hormone test and the human chorionic gonadotropin (HCG) test in the diagnosis of gonadotropin deficiency was studied in 73 boys referred because of delayed pubertal development or suspicion of gonadotropin deficiency. Hypogonadotropic hypogonadism was confirmed by clinical follow-up in 21 of the boys and excluded in the others because of normal pubertal development. Those latter boys served as a reference group. The post-HCG serum testosterone level was subnormal in hypogonadotropic hypogonadism on 12 of 19 occasions (in the reference group on two of 46 occasions) and the post-gonadotropin releasing hormone serum luteinizing hormone level was subnormal on fourteen of 22 occasions (zero of 65). Four of the seven boys with hypogonadotropic hypogonadism who had normal post-HCG testosterone levels had subnormal peak luteinizing hormone levels. Of the remaining three boys, two had low basal testosterone levels. Combining the two tests therefore improved the diagnostic accuracy.

Adolescent↗

Growth in Cushing syndrome.

Pre- and post-operative growth was analysed in eight children with Cushing syndrome. Six children had Cushing's disease; three of them were treated by bilateral adrenalectomy and three by transphenoidal pituitary adenectomy. One child had an adrenocortical adenoma and another primary adrenocortical nodular dysplasia. The typical cushingoid habitus was not always present during hypercortisolism. In contrast, abnormal deceleration of longitudinal growth and increase in relative weight were constant. The slowing of growth started 0.2-5.1 years before diagnosis. In four children these changes concurred. In three others the excessive weight gain preceded the slowing of growth, by 2.5-7.0 years. In one patient the deceleration appeared first; this was a girl with concomitant coeliac disease. This pattern of growth change occurring before (normal slowing of growth in) late puberty should raise the possibility of hypercortisolism. There was a suggestion of a better growth recovery in Cushing disease after pituitary adenectomy than after bilateral adrenalectomy.

Adolescent↗

Congenital Na+ diarrhea: a new type of secretory diarrhea.

We report a new type of congenital "secretory diarrhea" in a 9-year-old girl that led to contraction and severe metabolic acidosis in the first weeks of life. Her fecal Na+ concentration was high and the pH alkaline. All known causes of secretory diarrhea were excluded. Our findings indicate a defect in the handling of Na+ and H+ in the distal ileum and colon. Treatment with orally administered Na-K-citrate supplementation has normalized her fluid and electrolyte status and allowed normal growth and psychomotor development, but the diarrhea has persisted.

Acidosis↗

Gonadotropin-releasing hormone test and human chorionic gonadotropin test in the diagnosis of gonadotropin deficiency in prepubertal boys.

The discriminatory power of a gonadotropin-releasing hormone test and a human chorionic gonadotropin test in diagnosing gonadotropin deficiency was studied in 23 prepubertal boys with hypogonadotropic hypogonadism (HH). The boys were originally referred because of genital hypoplasia, delayed sexual maturation, or suspicion of HH. The diagnosis of HH was established clinically, in most cases after follow-up of several years. The results were compared with those of a reference group consisting of 44 prepubertal boys with incomplete testicular descent. Post-hCG serum testosterone level was the most sensitive discriminating variable, and was subnormal in 11 of 12 boys with HH (in one of 16 in the reference group). Post-GnRH serum LH concentration was the second most sensitive, and was subnormal in 15 of 23 boys with HH (two of the reference group). Our data indicate that post-hCG testosterone levels are of greater value than post-GnRH gonadotropin levels in the diagnosis of HH in prepubertal boys.

Adolescent↗

Selenium status of exclusively breast-fed infants as influenced by maternal organic or inorganic selenium supplementation.

A longitudinal dietary Se supplementation study on lactating mothers was performed to determine the possibilities of improving the Se status of exclusively breast-fed infants. A total of 200 mothers randomized into three groups received either no Se supplements, 100 micrograms of selenite, or 100 micrograms of yeast-Se daily. Maternal and infant serum Se concentrations showed a linear correlation during exclusive breast-feeding. Yeast-Se in the dose administered was safe and more effective than selenite in increasing the Se concentrations of maternal serum and milk, and infant serum. The mean estimated daily Se intakes of the infants were 7.7 +/- 2.2, 8.9 +/- 2.2, and 11.5 +/- 4 micrograms, in the control, selenite, and yeast-Se groups respectively. Though the infant Se intakes of the unsupplemented and selenite-supplemented mothers were below the lower limit of the safe and adequate range as set by the US National Research Council, their serum Se concentrations increased steadily over the 6-mo study period. As maternal serum Se also increased by over 50% during the same period the results suggest that a maternal daily intake of 50-75 micrograms is adequate during lactation.

Breast Feeding↗

Epidermal growth factor measurements in mouse plasma: method, ontogeny, and sex difference.

A highly sensitive mouse plasma (serum) epidermal growth factor (EGF) radioimmunoassay was utilized to determine EGF levels in mouse plasma and submandibular gland (SMG) at different ages. Plasma and serum levels were not different. Inferior vena caval blood was used because even at the age of 12 days EGF levels were markedly higher in neck blood. At 2 wk serum EGF levels were 60% of adult female levels. After a temporary decrease, mean EGF concentrations reached adult values at 31 and 60 days in the female but not yet in the male. In adults male serum EGF levels were twofold higher than female levels. This difference is parallel to but much smaller than the sex difference in SMG-EGF. SMG-EGF showed a very different ontogeny. Moreover, no correlation was present in the adults between the SMG and serum EGF concentrations. Testosterone treatment of adult females doubled their serum EGF levels, but the stimulated values were still below the mean of the male levels. The present observed plasma (serum) EGF levels in the mouse are 20-40% of previously reported values, probably because of the absence of EGF contamination from hair (urine) and milk.

Age Factors↗

Kinetics of the steroidogenic response to single versus repeated doses of human chorionic gonadotropin in boys in prepuberty and early puberty.

There is accumulating evidence that in adult men excessive amounts of gonadotropins induce testicular desensitization to further gonadotropin stimulus. We evaluated the effects of endogenous gonadotropins and of repeated doses of exogenous human chorionic gonadotropin (hCG) on steroidogenesis by studying prepubertal and pubertal boys. The boys received either two intramuscular injections of hCG 4 days apart (protocol I) or four injections at 3- to 4-day-intervals (protocol II). In protocol I, serum testosterone, 17 alpha-hydroxyprogesterone, and estradiol were measured basally and for 6 days after the second injection, and in protocol II, before each injection and 4 days after the last injection. In the prepubertal-boys, serum testosterone increased from very low basal levels to 10.3 (protocol I) and 8.3 nmol/liter (protocol II). In protocol I the increase after the first injection was 64-fold and in protocol II there was an increase after each injection to a final level 144-fold of the basal. No significant changes were seen in the estradiol levels. In the pubertal boys at genital stage G2, the serum testosterone levels increased after the first two injections, but at genital stage G3, the levels increased only after the first injection. Maximal testosterone increases were 27- and 8-fold, respectively. In pubertal boys estradiol levels increased progressively throughout the stimulation. The major testosterone response ws seen after the first dose of hCG and repeated doses, at least in the pubertal boys, increased estradiol but not testosterone levels, thus causing an estrogen-mediated 17,20-lyase block. We therefore suggest that a single-dose hCG test deserves further evaluation for diagnostic use.

17-alpha-Hydroxyprogesterone↗

Exclusively breast-fed healthy infants grow slower than reference infants.

We have studied the nutritional adequacy of exclusive breast-feeding by following prospectively the growth and protein nutrition of healthy infants during the 1st yr of life. The number of exclusively breast-fed infants was 116 at the age of 6 months and 36 at 9 months. These infants had slower length velocity after age 3 months than a comparison group of 32 infants who were weaned early and given formula plus solids. As a group, the exclusively breast-fed infants lagged slightly, but progressively, behind in relative length. By 9 months, 45% of them versus 18% of the comparison group showed a greater than 1 SD decrease in relative length. No such decrease was found in relative weight. Skinfolds and weight for length index showed that they were heavier for their length than the comparison infants. At 6 and 9 months the calculated protein intake (0.9 g/kg/day) was much less than the recommended amount (2.0 g/kg/day). Serum prealbumin concentration was lower than in the comparison group but this was noted as early as 4 months. No relation was found between the parameters of growth and protein nutrition either individually or in general. Whether the slower growth of the exclusively breast-fed infants represents appropriate physiological growth or whether it indicates nutritional deficiency is not known but we did not find any evidence of protein deficiency. Six infants did, however, show subsequent catch-up growth which could indicate previous malnutrition.

Breast Feeding↗

Epidermal growth factor in mouse ocular tissue: effects of thyroxine and exogenous epidermal growth factor.

Using a specific and sensitive epidermal growth factor (EGF) radioimmunoassay, we identified radioimmunoassayable EGF both in developing and adult mouse ocular tissues. In neonatal animals ocular EGF concentrations increase during the first 4-9 days and then decline between 9 and 15 days. Thyroxine (T4) administration (0.4 micrograms/g body weight/day from day 0) increased local EGF concentrations in eye and skin of 7-day-old neonatal mouse pups. However, this treatment did not affect submandibular gland EGF concentrations during the 1st wk of life. Both EGF and T4 are known to accelerate eye opening in the neonatal mouse. Exogenous EGF administration (2 micrograms/g body weight/day) during the first 8 days of life elicited precocious eyelid opening as expected but did not alter the serum T4 concentration, suggesting that EGF does not mediate eye opening by T4 dependent mechanism(s). Tissue EGF measurements revealed that the exogenous EGF was localized in skin and eye; however, other tissues including lung, liver, heart and submandibular gland also contained exogenous EGF. Kidney-EGF concentrations did not rise while brain-EGF levels were significantly decreased after exogenous EGF, suggesting that different EGF uptake and regulatory mechanism(s) exist in different tissues during the neonatal period. T4 administration (0.4 micrograms/g body weight/day) for 10 days to adult mice also increased ocular-EGF concentrations. However, this increase was abolished by sialoadenectomy, suggesting in contrast to the newborn, that submandibular gland is an important source of ocular-EGF in adult mice. These studies indicate that ocular EGF in the mouse is thyroxine responsive only during the neonatal period.

Animals↗

Urine and kidney epidermal growth factor: ontogeny and sex difference in the mouse.

We have explored the physiology of urinary epidermal growth factor (EGF) in the mouse by studying its ontogeny, and the effects of testosterone therapy on immunoreactive EGF (IR-EGF) concentrations in urine, kidney, serum and submandibular gland (SMG). Urine IR-EGF (U-EGF) increased about 100-fold relative to urea concentration and about 1000-fold relative to urine volume from the 1st day of life to adulthood. Most of this increase occurred between days 6 and 18, which is the known period of steep rise in plasma thyroid hormone concentration in the mouse. A small F greater than M sex difference was present in the adult. This difference was opposite in direction to the large M greater than F sex difference in adult SMG-EGF concentration. On day 26 (age of appearance of morphological sex difference in SMG) the sex difference was not yet present in urine, although in SMG it was even larger than in the adult. Kidney EGF concentration was low relative to U-EGF: 1 ml of adult urine contained approximately as much IR-EGF as 100 pairs of adult kidneys. In the adult, but not on day 26, there was a sex difference in kidney EGF concentration parallel to the sex difference in urine: female levels were about 30% higher than male levels. Ten days of testosterone treatment of adult female mice evoked an increase in IR-EGF concentration which was 1.7-fold for serum and 5-fold for SMG. In contrast, this treatment did not increase kidney or urine IR-EGF concentrations although kidney weight increased 1.3-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗