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Biomedical subjects

J Perheentupa

Publications and source records attributed to J Perheentupa.

At least 145 records · Page 8Linked to original sources

Single versus repeated dose human chorionic gonadotropin stimulation in the differential diagnosis of hypogonadotropic hypogonadism.

The responses of serum testosterone (T), 17 alpha-hydroxyprogesterone, and 17 beta-estradiol (E2) to four im injections of hCG (5000 IU/1.7 m2) given on days 0, 4, 7, and 10 were studied in 10 prepubertal and 10 pubertal boys with hypogonadotropic hypogonadism (groups O and P, respectively). Serum was obtained before each injection and on day 14. The results were compared with those of controls, 16 prepubertal boys with incomplete testicular descent and 6 pubertal boys with constitutional delay of puberty. Serum T levels increased significantly in groups O and P to 2.0 and 4.6 nmol/liter, respectively, after the first injection, then progressively to 5.8 and 11.2 nmol/liter. Basal T levels of group O did not differ from those of the controls, but were subnormal for group P (P less than 0.001). Stimulated T levels were subnormal in both groups (P less than 0.01 and P less than 0.001), but repeated doses increased the difference from the control value only in group P. A difference in E2 response between patients and controls appeared in puberty; only the pubertal control boys had substantial increases in E2 (P less than 0.001). Our results show that the optimal protocol for a diagnostic hCG test in prepubertal boys is a single dose of hCG, with determination of T levels 4 days later. In puberty, if the basal T levels are inconclusive, repeated doses of hCG should be given with determination of both T and E2. These findings also suggest that the full inhibitory effect of E2 on T synthesis results from a pubertal maturation process, possibly induced by endogenous gonadotropins, which cannot be induced by two weeks of hCG stimulation in prepubertal boys or those with hypogonadotropic hypogonadism.

17-alpha-Hydroxyprogesterone↗

Epidermal growth factor in human urine from birth to puberty.

The highest concentrations of epidermal growth factor (EGF) are found in urine, but the physiological role of urinary EGF is unknown. We studied human urinary EGF excretion, by measuring its concentration with a specific homologous RIA, in 265 healthy children from birth until age 16 yr. The absolute concentrations varied widely between individuals. Mean values were approximately 10 ng/ml in 1- to 30-day-old infants; 2.5-fold higher values were found in infants aged 2 to 12 months. During the second year there was a further rise to about 70 ng/ml, and urinary EGF excretion was in the same range in older subjects. The EGF/creatinine concentration ratio was less variable. The mean ratio increased 6-fold from birth to the second year of life. Thereafter, the EGF/creatinine ratio decreased gradually to one-third of the peak level at puberty. No sex difference was found.

Adolescent↗

Epidermal growth factor in mouse urine: non-blood origin, and increase by sialoadenectomy and T4 therapy.

To study the origin and regulation of urinary epidermal growth factor (U-EGF), we measured EGF in adult female mouse plasma, urine and kidney tissue. We also studied the effects of excision of the submandibular salivary gland (SMG) and, after SMG excision and sham operation, 10-day therapies with T4 (0.4 microgram/g daily), testosterone propionate (TP, 12.5 micrograms/g every 48 h), and SMG extract (25 micrograms EGF daily). We measured EGF with a specific liquid phase radioimmunoassay. The mean apparent urinary clearance was 150-fold higher for EGF than for urea. U-EGF was increased 24 h after the last sc injection of SMG extract. SMG excision caused a 2.2-fold increase in U-EGF and in apparent EGF clearance. T4 brought about a 1.5 to 1.75-fold increase in U-EGF while TP was without effect. Kidney EGF (K-EGF) responded to T4 and TP like U-EGF, but SMG excision and extract were without effect on K-EGF. We conclude that 1) the immunoassayable EGF in blood plasma and SMG-EGF do not appear to be major sources of U-EGF but plasma EGF may be a minor source, 2) kidney tissue appears not to be a major source of U-EGF, 3) production of U-EGF is activated by SMG excision, 4) T4 increases both U- and K-EGF while testosterone has no effect.

Animals↗

Acquisition of urine, kidney and submandibular gland epidermal growth factor responsiveness to thyroxine administration in neonatal mice.

Thyroxine (T4) administration to newborn mice on days 0-6 produced no measurable changes of submandibular gland (SMG) or kidney epidermal growth factor (EGF) concentrations on day 7, compared with vehicle-treated control pups. By contrast, this regimen caused a large increase in urine EGF levels. The effects of three T4 injection regimens (on days 0-6, 7-14 and 0-14) were then studied on day 15. The 0-14 and 7-14 day-regimens elicited large increments in urine, SMG and kidney EGF concentration, the 0-14 day-regimen having the greatest effect. The 0-6 day-regimen had no effect on SMG and kidney EGF concentrations on day 15 but did increase urine EGF. In summary, urine EGF responsiveness to T4 is present during the first week of life, but SMG and kidney EGF responsiveness develops only in the second week. Administration of T4 appears to accelerate the normal ontogeny of urine, kidney and SMG EGF.

Aging↗

Biotin concentrations in maternal plasma and milk during prolonged lactation.

We followed a group of exclusively breast feeding mothers for 12 months after delivery. They numbered 200 at delivery, 140 at 4 months of lactation, 116 at 6, 36 at 9 and 7 at 12 months. The milk concentration of biotin was very low at delivery and subsequently the (geometric) mean value remained at around 4.5 micrograms/l. The mean plasma value was 250 ng/l at delivery and stable (around 330 ng/l) throughout the lactation. There were large intra- and interindividual variations in the concentrations in both milk (from 0 to 27 micrograms/l) and plasma (from 142 to 1090 ng/l). The variations in the milk concentrations result in a similar variation in the biotin intake of the exclusively breast-fed infants. The current recommendations for biotin intake were not met by any of those infants but no manifestations of biotin deficiency were recorded.

Biotin↗

Acquisition of submandibular gland nerve growth factor (SMG-NGF) responsiveness to thyroxine administration in neonatal mice.

The growth of the submandibular gland (SMG) was studied in newborn mice from birth to 15 days of age. Progressive changes in wet weight were observed to accompany changes in biochemical constituents such as RNA, protein, and lipid. Thyroxine (T4) administration from days 0-6 produced changes in SMG growth and SMG accumulation of RNA, protein, and lipid components relative to control pups treated with a similar volume of vehicle. This hormone regimen produced no measurable changes in SMG nerve growth factor (SMG-NGF) concentration. T4 responsiveness also was studied from days 0-15. Three patterns of T4 injection (from days 0-6, 7-14, and 0-14) were found to elicit a differential response in the three biochemical constituents measured, but treatment from days 7-14 and 0-14 elicited precocious increments in SMG-NGF concentrations on day 15. The effect of T4 injection from birth was more effective in augmenting SMG-NGF concentration than hormone treatment initiated from days 7-14. A persistent T4 effect on SMG-NGF also was observed on day 21 following hormone treatment from days 7-14 or 0-14. In summary, the acquisition of SMG-NGF responsiveness to T4 appears to develop during the neonatal period. The administration of T4 during this period also precociously stimulates the mechanisms that govern the normal ontogeny of SMG-NGF at the time of weaning.

Age Factors↗

Finnish national screening for hypothyroidism. Few false positives, early therapy.

National cord blood screening for congenital hypothyroidism has operated in Finland with complete coverage since 1980. A low frequency of false positives, 0.08%, was achieved by supplementing the TSH screen with a T4 determination in borderline samples. Among 175188 infants the incidence of (unconfirmed) hypothyroidism was 1/2637. The median age at start of therapy was 6 days. The programme imposed a 2-3 week therapy on the false positive cases. This did not appear to cause any adverse effects. A mechanism for masking congenital hypothyroidism was observed: two athyroid infants were euthyroid at birth because of feto-fetal transfusion.

Congenital Hypothyroidism↗

Exclusive breast-feeding for 9 months: risk of iron deficiency.

Thirty-six infants who were exclusively breast-fed were observed for 9 months. Thirty-two infants who were completely weaned prior to age 3 1/2 months served as controls; these infants received iron supplementation in formula and solid foods. A great majority of exclusively breast-fed infants were able to maintain their iron status at the same level as that of the control infants. The mean concentration of hemoglobin was higher in breast-fed infants than in control infants at ages 4 and 6 months. However, six breast-fed infants required iron medication because they had laboratory evidence of iron deficiency, although none had anemia. Maternal iron supplementation during breast-feeding, even in large daily doses, did not have any effect on the infants' iron nutrition, nor prevent infants from developing some signs of iron deficiency. Our data indicate that it is safe in exclusively breast-fed infants to shift the starting age for introduction of iron to 6 months.

Adult↗

A novel format for a growth chart.

A novel format for a growth chart is proposed to facilitate early detection of aberrant growth. Normal growth is shown as a horizontal line and any deviation from this indicates abnormal change in growth. The vertical scales show relative height (height SDS) and relative weight (% deviation of weight from the mean weight for height) directly. Weight is recorded against height rather than age.

Adolescent↗

Hypergonadotropic hypogonadism in newborn males with primary testicular failure.

Four infants with genital ambiguity but with apparent testes were given a gonadotropin-releasing hormone (GnRH) test and a human chorionic gonadotropin (hCG) test at age 3-12 days. The results were compared with those from 16 newborn males (aged 2 to 6 days) with minor genital anomalies; 9 with unilateral and 3 with bilateral incomplete testicular descent, 2 with surgically insignificant glandular hypospadias and 2 with penis length less than (means-2 SD) for gestational age. Treatment with testosterone resulted in clear phallus growth in all four patients. All four patients had elevated basal luteinizing hormone (LH) concentrations as well as an exaggerated LH response to GnRH; three of them also had an exaggerated follicle stimulating hormone (FSH) response. Thus in all patients the etiology of genital ambiguity was considered to be testicular. The testosterone response to hCG was normal in two of the patients but impaired in the other two. The steroidogenic response did not show any specific enzyme defect. We conclude that newborn boys with Leydig cell failure are clearly hypergonadotropic, the GnRH test is a more sensitive indicator of Leydig cell failure neonatally than the hCG test and normal testes greatly inhibit the secretion of both LH and FSH during the first week of life.

Chorionic Gonadotropin↗

Epidermal growth factor in neonatal mouse urine: maturative effect of thyroxine.

Using a specific and sensitive epidermal growth factor (EGF) radioimmunoassay, we have shown measurable quantities of EGF in mouse urine during the neonatal period. Sephadex G-50 column chromatography demonstrated the presence of a single immunoreactive component at the position defined by standard EGF (mol wt 6045). Comparison of urine urea nitrogen and urine EGF levels in neonatal and adult mice showed adult values to be 3- and 16-fold higher, respectively. Kidney weights relative to body weight were similar in newborn and adult animals while kidney EGF concentration per mg protein was 2.5-fold higher in the adult. The relative submandibular gland (SMG) weight was slightly higher in adult female mice than in the newborn, whereas SMG-EGF concentration was 15,000-fold higher in the adult than in the newborn. Thyroxine administration to neonatal mice from day 0 to day 6 increased urine EGF concentration 7-fold compared to control pups. Though the hormone treatment elicited a significant increase in relative SMG weight, its EGF concentration like that of the kidneys remained unchanged. The results suggest that urine EGF is subject to thyroid hormone modulation in newborn animals and that the changes in urine EGF concentration are independent of changes in SMG and renal EGF levels.

Animals↗

Responsiveness of the pituitary-testicular axis to gonadotropin-releasing hormone and chorionic gonadotropin during the first week of life.

Qualitative changes are known to occur in testicular steroidogenesis at birth as the testosterone peak is reached without significant elevation of basal luteinizing hormone in the 2nd wk of life. This study was designed to evaluate testicular activity prior to these changes. Pituitary-testicular function was studied by measuring serum gonadotropins and steroids after stimulation by gonadotropin-releasing hormone (GnRH) (one intravenous injection) and human chorionic gonadotropin (hCG) (three intramuscular injections). The subjects had minor genital anomalies; their ages ranged from 2 to 6 days. All had a strong luteinizing hormone response and a weaker follicle-stimulating hormone response to GnRH stimulation. hCG induced significant increases in serum pregnenolone, 17-hydroxyprogesterone, androstenedione, testosterone, and dihydrotestosterone. Serum estradiol and estrone did not change, and progesterone decreased. The results clearly show that the pituitary-testicular axis is functional neonatally. The responsiveness of the testis to hCG supports the assumption that the postnatal decrease of testicular steroids is due to the simultaneous disappearance of hCG from the circulation. The neonatal testis does not show any estradiol response to hCG, which is a feature typical of prepuberty.

Chorionic Gonadotropin↗

Growth hormone increases neonatal mouse urine epidermal growth factor.

The effects of bovine growth hormone (bGH) and triiodothyronine (T3), alone and in combination, were studied on urinary-EGF (U-EGF) in newborn mice. All three treatments significantly augmented the concentration of U-EGF. The effect was far greater for T3 than for bGH. No EGF response was seen in submandibular gland or kidney tissues suggesting that, in newborn animals, these hormones selectively modulate U-EGF.

Animals↗

Hormonal modulation of mouse plasma concentration of epidermal growth factor.

To understand the physiological role of plasma epidermal growth factor (EGF) we studied in adult female mice the effect of endocrine manipulations on serum EGF concentration (S-EGF). Starting 1 month after sham operation (sh) or excision (SX) of the submandibular salivary gland (SMG), groups of 6 mice were given sc injections of T4 (0.4 micrograms/g daily), testosterone propionate (TP, 25 micrograms/g every 48 h), T4 + TP, or SMG extract (20 micrograms EGF daily) for 10 days. They were exsanguinated via the abdominal vena cava on day 11. During treatment the SX mice gained 55% less weight and their S-EGF was 25% lower compared with the sh mice. Hormone effects were clear in the SX mice: T4 caused a 35% decrease in S-EGF and a 5-fold increase in SMG-EGF concentration. TP caused a 1.6-fold increase in S-EGF and a 6-fold increase in SMG-EGF. Twenty-four hours after the last injection of SMG extract S-EGF remained 1.6-fold elevated. We conclude that plasma EGF is largely independent of SMG, and is modified by hormones in ways different from known tissue effects. This is consistent with an endocrine role of EGF.

Animals↗

Oral administration of urea cycle intermediates in lysinuric protein intolerance: effect on plasma and urinary arginine and ornithine.

In lysinuric protein intolerance, an autosomal recessive disorder of amino acid transport, oral citrulline increases the plasma concentration of urea cycle intermediates more than does oral arginine or ornithine. The clinical improvement suggests that citrulline affords the best means of correcting the ornithinopenic malfunction of the urea cycle.

Administration, Oral↗

Oral administration of epsilon N-acetyllysine and homocitrulline in lysinuric protein intolerance.

The defect of epithelial diamino acid transport in lysinuric protein intolerance (LPI) results from an abnormality of the basolateral cell membranes. Therefore the lysine deficiency, which is one of the consequences of this defect, cannot be corrected by oral administration of lysine, either in free or peptide form. In search of useful lysine derivatives, we studied in patients with LPI the absorption after oral administration of homocitrulline and epsilon N-acetyllysine. Acetyllysine, but not homocitrulline, normalized the subnormal plasma lysine concentrations.

Administration, Oral↗