The role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in pathogenesis of dengue hemorrhagic fever (DHF).

In previous studies it has been demonstrated that the levels of plasma 6 keto-prostaglandin F1 alpha (6-K-PGF1), the stable metabolite of PGI2 were elevated in DHF patients during shock. In this study it is hypothesized that excessive PGI2 production plays a very important role in developing serious clinical manifestations of dengue shock syndrome (DSS) patients. In addition, an attempt was made to determine whether TXA2 has any significant role in such patients. Plasma 6-K-PGF1 and thromboxane B2 (TXB2), the stable metabolites of TXA2 were determined in 43 normal healthy children (NC) and 54 DHF patients without shock (DHF-N) and 33 DHF patients with shock (DHF-S). Subjects aged between 2 and 14 years. Plasma 6-K-PGF1 and TXB2 were measured by radioimmunoassay and the ratio of TXB2/6-K-PGF1 were also calculated. In 43 NC the values of plasma TXB2, 6-K-PGF1 and TXB2/6-K-PGF1 ratio were (mean +/- SE) 372.3 +/- 17.1, 150.1 +/- 2.4 and 2.52 +/- 0.12 pg/ml, respectively. In 54 DHF-N patients the corresponding values were 409.1 +/- 16.0, 278.4 +/- 11.6 and 1.54 +/- 0.06 pg/ml; whereas those in 33 DHF-S patients were 254.3 +/- 26.2, 349.1 +/- 20.5 and 0.757 +/- 0.073 pg/ml, respectively. Plasma 6-K-PGF1 levels of DHF-N and DHF-S patients were significantly greater than those in normal children (p < 0.001, p < 0.01 respectively). The plasma 6-K-PGF1 levels seem to be greater in DHF-S patients than in the DHF-N patients, however the difference in values were not statistically significant (p > 0.05). These findings indicate that plasma PGI2 level is significantly increased in DHF particularly during shock. Plasma TXB2 levels of DHF-N had no significant statistical difference from those of NC (p > 0.05); however, those in DHF-S patients were significantly lowered (p < 0.001) than those of NC and DHF-N patients. The findings suggest the important role of TXA2 to compensate for excessive PGI2 secretion in DHF patients. The failure or inadequate TXA2 production may eventually lead to shock. The ratios were significantly reduced in both DHF-N and DHF-S patients when compared to those of NC (p < 0.001 both). The ratio in DHF-S patients was also significantly lowered than that in DHF-N patients (p < 0.001). It is suggested that the imbalance between TXA2 and PGI2 production exists during DHF infection. The more reduction of plasma TXA2/PGI2 ratio leads to more overt and serious clinical manifestations of the disease.

Combined raw cornstarch and nifedipine as an additional treatment in persistent hyperinsulinemic hypoglycemia of infancy.

This study reports the result of treatment with the combination of raw cornstarch and nifedipine in two infants affected with hyperinsulinemic hypoglycemia of variable severity. The first infant developed hypoglycemia during early neonatal period and required subtotal pancreatectomy. She still developed hypoglycemia after her second operation. The second infant developed hypoglycemia at the age of 7 months. Raw cornstarch and nifedipine efficiently normalized both infants' blood glucose levels. Although they still need frequent feedings, no hypoglycemic episode was reported except when they were sick. Their growth and development were markedly improved after initiation of treatment.

Gonadotropin-releasing hormone testing in premature thelarche.

Premature thelarche (PT) is characterized by isolated breast development in girls prior to 8 years of age. In addition, there is neither growth spurt nor advanced bone age. It has been suggested that luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) alone is adequate to distinguish central precocious puberty from PT. However, LH response to GnRH is greater in infancy than that in childhood. Therefore, gonadotropin response to GnRH in girls with isolated premature breast development in different age group was studied. Thirty-six girls with isolated PT (aged 0.25-8 years) were evaluated. They were classified into 2 groups; aged < 4 years (group A: mean age 1.57 +/- 0.87 years, n = 13) and > or = 4 years (group B: mean age 6.97 +/- 0.94 years, n = 23). Initial evaluation included X-ray bone age, pelvic sonography and GnRH testing. Patients were followed for at least 1 year to confirm that no patient had progression into puberty. Bone ages in both groups were within mean +/- 2 SD in all patients. Pelvic sonography was performed in all patients which revealed no abnormality of ovaries and uterus. Pubertal response to GnRH stimulation is characterized by peak LH of > 20 IU/L or delta LH of > 15 IU/L which is generally greater than peak follicle stimulating hormone (FSH) or delta FSH, respectively. Mean peak LH and delta LH in group A were 13.0 +/- 6.06 and 11.4 +/- 5.92 IU/L whereas those in the group B were 8.5 +/- 4.10 and 6.3 +/- 3.49 IU/L. Therefore, LH response to GnRH in group A was significantly higher than that in group B (p < 0.05). In addition, the mean peak FSH and delta FSH in group A were 120.5 +/- 45.87 and 109.9 +/- 42.09 IU/L whereas those in the group B were 48.7 +/- 24.05 and 39.9 +/- 23.69 IU/L. Therefore, FSH response to GnRH in group A was significantly greater than that in group B (p < 0.001). LH response to GnRH alone can distinguish prepuberty from puberty in girls > 4 years of age. However, in prepubertal young girls with PT aged < 4 years, pubertal LH response can occur, i.e. peak LH > 20 IU/L. Hence, the greater FSH response to GnRH than that of LH would confirm the diagnosis of premature thelarche in this group. Therefore, the evaluation of FSH response to GnRH is beneficial to distinguish puberty from prepuberty in young girls.

Insulin-like growth factor-I (IGF-I) screening for the diagnosis of growth hormone (GH) deficiency.

Growth hormone deficiency (GHD) is a common cause of growth retardation in children and adolescents. Gold standard for the diagnosis of GHD is based upon two standard growth hormone (GH) provocative tests demonstrating a peak serum GH of less than 7 ng/mL. These tests, besides requiring multiple blood samplings, are time-consuming and costly. GH primarily mediates its growth-promoting effect through insulin-like growth factor-I (IGF-I). Hence, basal serum IGF-I level reflects GH status. We studied 47 prepubertal children with or without short stature. Aged ranged between 4.3 and 15.6 years. They were divided into 2 groups based upon 2 standard GH provocative tests. Seventeen Children were classified as having GHD. The remaining 30 were non-GHD. Basal serum IGF-I was obtained before GH testing. The means +/- SE (range) of serum IGF-I concentration were 44.26 +/- 3.19 (19.10-75.63) ng/mL in GHD and 118.42 +/- 10.03 (60.65-235.91) ng/mL in non-GHD which were significantly different (P < 0.001). 88.2 per cent of GHD had serum IGF-I concentration less than 60 ng/mL whereas 100 per cent of non-GHD had serum IGF-I greater than 60 ng/mL. There was no correlation between serum IGF-I and either bone age or chronologic age in children with GHD. These data indicate that serum IGF-I level is a useful screening test to exclude GHD with high sensitivity. We suggest that if serum IGF-I is less than 80 ng/mL in prepubertal children, GH provocative tests should be performed to diagnose GHD. If serum IGF-I is greater than 80 ng/mL, growth rate monitoring is recommended. If growth rate is decreased despite normal IGF-I, GH provocative tests should be obtained to rule out GHD.

Prolactin (PRL) release in normal and growth hormone deficient children after oral metoclopramide.

Studies were done to determine plasma PRL in response to oral MC 0.2 mg/kg in 17 normal children (NC), 12 males and 5 females aged between 4.7-12.8 years and in 26 idiopathic growth hormone deficient children (IGHD), 15 M, 11 F, between 1.5-14.7 years old. Peak serum GH levels above 10 ng/ml after clonidine test and during insulin induced hypoglycemia were used to distinguish these 2 groups. None of the subjects had secondary sex characteristics. Adrenocortical and thyroid disorders were excluded. The subjects were fasted overnight. Blood samples for PRL determination were obtained at 0, 60, 90, 120 min after oral MC. In 17 NC the basal serum PRL values ranged from 0 to 19.2 ng/ml with the mean +/- SE of 7.24 +/- 1.7 ng/ml. The peak serum PRL response to MC ranges were from 33 to 127 ng/ml with the mean +/- SD and +/- SE of 64.45 +/- 24.22 and +/- 5.88 ng/ml respectively giving the cut point-2SD value of 16.01 ng/ml. Among 26I GHD, only 2 patients (7.69%) being all male, had peak PRL response to MC below 16.01 ng/ml, whereas, the rest (92.31%) had peak PRL levels above it. It is concluded that oral MC 0.2 mg/kg is the potent PRL stimulator in children, which can be safely used to test pituitary PRL secretion effectively. The majority (92.31%) of idiopathic GH deficient children had adequate serum PRL response to oral MC, whilst 7.69 per cent disclosed inadequate response which might indicate different etiologies.

Congenital complete absence of GH, TSH and PRL in infants: a consequence of Pit-1 gene deletion.

The patient was the first child of a short mother (140 cm) born at term with a birthweight of 2,700 g. On arrival, she was 1 4/12-year-old, weighed 4,150 g and 47 cm long. Her bone age was at the 6 month-old level. Endocrine investigation revealed undetectable plasma growth hormone (GH), thyrotropin (TSH) and prolactin (PRL) levels. CT scan of ovaries revealed bilateral ovarian agenesis in spite of normal, 46 XX karyotype. MRI of the brain did not demonstrate intracranial tumor or congenital malformation. Peak plasma GH level after oral clonidine provocation, insulin induced hypoglycemia, and I.V. GH-RF stimulation were 0.6, 0, and 0 ng/ml respectively. Peak plasma TSH response after I.V. TRH stimulation was 0.04 microU/ml. The patient could not secrete PRL at any time after insulin induced hypoglycemia, TRH and metoclopramide stimulations. On the other hand the child had elevated basal plasma cortisol (38 micrograms/dl at 8.00 AM) and raised 24 hr urinary 17 OHCS excretion (50 mg/1 g Cr against normal value of 3 mg/1 g Cr) without evidence of Cushing syndrome probably indicate partial glucocorticoid resistance. Peak plasma cortisol responses after intravenous metoclopramide and insulin induced hypoglycemia were 46 and 42.9 micrograms/dl respectively. Dexamethasone administration reduced plasma cortisol to 2.9 micrograms/dl. The child had also elevated basal plasma FSH (36 microU/ml) and LH (5 microU/ml) with further elevation to the peak of 123 and 99 microU/ml respectively after LHRH stimulation. All evidence suggested the diagnosis of congenital complete absence of GH, TSH, and PRL which is characteristic of Pit-1-gene deletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma prostacyclin (PGI2) in dengue hemorrhagic fever.

Dengue hemorrhagic fever (DHF) is an epidemic viral disease. The exact mechanism attributable to platelet and vascular dysfunctions is still obscure. Plasma 6-keto-PGF1a (6KPGF1), the stable metabolite of PGI2 was determined in 60 DHF patients and in 11 non-DHF (NDHF) patients with fever of over 38.5 degrees C to compare with that of 33 normal children (NC) in the same age group (2-15 years). Among 60 DHF patients, 32 had blood obtained during impending shock, whereas blood samples of the remainder were taken during normotension. Their plasma 6 KPGF1 values (mean +/- SE) were 201.06 +/- 12.42 and 132.87 +/- 13.08 pg/ml respectively. All patients had serology positive for acute dengue viral infection. The plasma 6 KPGF1 (mean +/- SE) of 33 NC and 11 - NDHF subjects were 149.82 +/- 4.93 and 108.69 +/- 14.53 respectively. The plasma 6KPGF1 levels of 32 DHF patients with impending shock were significantly higher than those of 28 normotensive DHF patients (p less than 0.005), 33 NC (p less than 0.005) and 11 - NDHF patients (p less than 0.005). However the levels in 28 normotensive DHF patients are not statistically different from the values of 33 NC and 11 - NDHF patients. It is concluded that there is a tendency of excessive PGI2 production in DHF patients during hypotensive crisis.

Growth hormone release in normal children after oral clonidine 4 micrograms/kg.

Oral clonidine 4 micrograms/kg was given to 32 normal children, 18 males and 14 females with the mean age of 8.44 +/- 3.18 years. All were healthy and had normal growth. They were fasted overnight and throughout the test. Blood specimens were taken in the morning at 0, 30, 60, 90 and 120 minutes after clonidine ingestion. The mean basal plasma GH level was 1.81 +/- 2.07 ng/ml. The range of peak GH response was 18.7-67.3 ng/ml mostly at 90 minutes after clonidine with the mean value of 30.92 +/- 10.97 ng/ml. There were no serious undesired effects. It is concluded that with the oral dose of 4 micrograms/kg, clonidine is a safe and potent GH provocative agent with reliable and satisfactory results.

X-linked congenital adrenal hypoplasia: proposal pathogenesis.

Two male infants with hyperpigmentation, vomiting, lethargy and weight loss were reported. Hypoglycemia, hyponatremia, hypochloremia, hyperkalemia and metabolic acidosis were suggestive diagnosis of salt losing adrenocortical insufficiency. The absence of ambiguous genitalia, low 24 hour urinary 17 KS and pregnanetriol excretion precluded congenital adrenal hyperplasia. Low basal levels of plasma aldosterone and cortisol and low 24 hour urinary 17 OHCS excretion with disability to increase their corticosteroid secretions after ACTH stimulation as well as furosemide and theophylline infusions were supportive for the diagnosis of congenital adrenal hypoplasia. The definitive diagnosis was confirmed by ultrasonogram and computerized tomography. Family histories suggested X-linked recessive inheritance in these reported cases. Evidence of progressive postnatal adrenocortical degeneration was documented by progressive deterioration of adrenocortical functions beginning from mineralocorticoid to total corticosteroid deficiencies. The increased brain serotonin synthesis as the associated pathology of X-linked congenital adrenal hypoplasia was proposed on the basis of elevated basal plasma GH and PRL levels in the reported cases, taken together with an incidence of congenital LH deficiency and persistent ACTH hypersecretion in corticosteroid treated patients reported elsewhere.