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Biomedical subjects

T Aceto

Publications and source records attributed to T Aceto.

At least 19 recordsLinked to original sources

Renal structural-functional relationships in early diabetes mellitus.

To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5-12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: "glomerular size" correlated with patient age, CCr, and UAE; "peripheral capillary decrease" correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; "mesangial increase" correlated with UAE; and "interstitial scarring" correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.

Adolescent↗

Sleep apnea in patients receiving growth hormone.

Among 145 patients treated with recombinant human growth hormone (GH), four developed sleep apnea (two obstructive, two mixed) associated with tonsillar and adenoidal hypertrophy in three. These four patients had no local risk factors predisposing to upper airway obstruction (i.e., frequent pharyngitis or sinusitis). Clinical and/or polysomnographic features of sleep apnea improved following cessation of GH therapy in one patient, and following tonsillectomy and adenoidectomy in all patients. The present observations indicate that, albeit rarely, obstructive and/or central sleep apnea may occur in children treated with GH. Polysomnography should be considered if symptoms of snoring, interrupted sleep, daytime somnolence-particularly if associated with tonsillar hypertrophy-appear in children during GH therapy.

Adenoidectomy↗

The relationship between luteinizing hormone and estradiol secretion in female precocious puberty: evaluation by sensitive gonadotropin assays and the leuprolide stimulation test.

We used the GnRH agonist (GnRHa) stimulation test (20 micrograms/kg leuprolide sc, followed by 24-h serial sampling) to investigate the relationship between gonadotropin and estradiol (E2) secretion in the early phase of female central precocious puberty (CPP). Girls with CPP and moderately increased (early pubertal) peak E2 concentrations after GnRHa stimulation (136 +/- 11 pmol/L; range, 92-176; group B; n = 7) were compared to girls with CPP and higher (midpubertal) peak E2 responses to GnRHa (mean +/- SE, 590 +/- 63 pmol/L; range, 235-1189; group C; n = 19) and to a group of subjects with no breast development and a prepubertal hypothalamic-pituitary-gonadal axis (peak E2 response to GnRHa, 39 +/- 7 pM/L; range, 18-62; group A; n = 6). Compared to group A subjects, patients in group B had similar (P > 0.2) peak GnRHa-stimulated LH concentrations (B, 4.8 +/- 1 IU/L; A, 2.3 +/- 0.5 IU/L) and peak nocturnal LH (B, 0.81 +/- 0.2; A, 0.25 +/- 0 IU/L), but higher peak GnRHa-stimulated FSH concentrations (B, 26 +/- 7; A, 11 +/- 2 IU/L; P < 0.05) and mean nocturnal FSH (B, 4.2 +/- 1; A, 1.1 +/- 0.3 IU/L; P < 0.05) concentrations. Compared to group B, group C patients had higher (P < 0.001) GnRHa-stimulated peak LH (67 +/- 19 IU/L) and higher (P < 0.05) peak nocturnal LH (9.7 +/- 2.9 IU/L) concentrations, but similar GnRHa-stimulated peak FSH (27 +/- 3 IU/L) and mean nocturnal FSH (3.8 +/- 0.5 IU/L) levels. Group C patients with a ratio of peak GnRHa-stimulated LH to FSH concentrations below or above 1, respectively, had similar peak E2 responses to GnRHa (516 +/- 80 vs. 644 +/- 92 pM/L; P > 0.1). Stepwise regression analysis indicated that the peak LH response to GnRHa (r = 0.76; P < 0.001), but none of the FSH secretory parameters (P > 0.10), affected the E2 response to GnRHa. These data suggest that girls with CPP in the early phase of activation of the hypothalamic-pituitary-gonadal axis are capable of clinically relevant E2 production, which may occur in the face of low LH secretion and low LH/FSH ratios and cannot be explained solely on the basis of increased FSH secretion. Thus, endocrine or paracrine factors other than gonadotropins may be important in amplifying E2 secretion in the early phase of CPP.

Child↗

The pattern of gonadotropin and estradiol secretion in exaggerated thelarche.

PURPOSE: To assess the dynamics of the pituitary-ovarian axis in exaggerated thelarche, defined as premature thelarche associated with signs of systemic estrogen effects (advanced bone age and/or growth acceleration) without progression to complete puberty. SUBJECTS AND METHODS: Seven girls (age < 2.5 years) with exaggerated thelarche, 6 girls with inactive pituitary-ovarian axis (premature adrenarche) and 21 girls with activated axis (central precocious puberty) had serum FSH, LH and E2 measured serially before and 1 to 24 h after gonadotropin-releasing hormone agonist (GnRHa) administration (leuprolide, 20 micrograms/kg sc), used as a test of combined pituitary-ovarian stimulation. RESULTS: Although girls in the exaggerated thelarche and adrenarche group had similar [mean (SEM)] baseline FSH [3.2 (0.9) vs 1.4 (0.3) IU/l], LH [0.36 (0.1) vs 0.27 (0.02) IU/l] and E2 [20 (1.2) vs 21 (2) pmol/l] concentrations, and similar peak post-GnRHa LH concentrations [5.5 (1.1) vs 2.4 (0.5) IU/l], girls with exaggerated thelarche achieved higher peak FSH [41 (9) vs 14 (3) IU/l, p < 0.01] and E2 [243 (40) vs 37 (6) pmol/l, p < 0.001] concentrations after GnRHa. In comparison to patients with exaggerated thelarche, girls with precocious puberty had higher (p < 0.01-0.001) baseline LH [3.6 (0.8) IU/l], baseline E2 [69(11) pmol/l], GnRHa-stimulated peak LH [68 (17) IU/l] and peak E2 [648 (58) pmol/l] concentrations, but similar FSH parameters. CONCLUSIONS: Girls with exaggerated thelarche exhibit substantial E2 secretory potential that can be demonstrated by GnRHa stimulation, is predominantly FSH-driven, and probably accounts for the manifestations of estrogen effect seen in these girls.

Analysis of Variance↗

Serum luteinizing hormone concentrations, as measured by a sensitive immunoradiometric assay, in children with normal, precocious or delayed pubertal development.

To determine the diagnostic potential of a highly sensitive immunoradiometric assay (IRMA) for LH in children with normal puberty or altered tempo of sexual maturation, we compared serum LH levels by IRMA (LH IRMA) and standard RIA (LH RIA) in children with idiopathic precocious thelarche (IPT; n = 6), idiopathic premature adrenarche (IPA; n = 14), central precocious puberty (CPP; n = 15), and constitutional delay of puberty (DP; n = 15), and 160 control children (79 males and 81 females). Subjects in the latter group were staged, according to their genital or breast development, as early prepubertal (P1E; age, less than 8 yr), late prepubertal (P1L; 8-12 yr), or stage II-V (P2-P5; n = 22-34 for each subgroup). Serum LH IRMA levels in P1E, IPT, and IPA children were either undetectable (95% of subjects less than 0.25 IU/L) or barely detectable (5% of subjects, less than or equal to 0.5 IU/L). Serum LH IRMA levels were greater than 0.5 IU/L in 38% of P1L (mean +/- SD for the group, 1.0 +/- 1.3 IU/L) and 57% of P2 (1.4 +/- 1.3 IU/L); they were greater than 1.0 IU/L in 100% of P3 (2.6 +/- 1.3 IU/L), P4 (3.9 +/- 2 IU/L), and P5 (8.6 +/- 4 IU/L) children. Comparison of serum LH levels between contiguous pubertal stages showed significantly higher LH IRMA concentrations in P3 vs. P1E, P4 vs. P2, P5 vs. P4 (all P less than 0.001), and P3 vs. P1L (P less than 0.05). In contrast, LH RIA values were not significantly different in P1E (2.0 +/- 0.6 IU/L), P1L (2.3 +/- 0.6 IU/L), P2 (2.7 +/- 0.9 IU/L), P3 (3.2 +/- 1.3 IU/L), and P4 (3.7 +/- 2.2 IU/L), although they were higher in P5 (6.8 +/- 4 IU/L) than in P4 (P less than 0.001). From P1E to P5 LH IRMA levels increased 38-fold in females and 21-fold in males, while LH RIA increased 4- and 2.1-fold, respectively. Serum LH IRMA correlated significantly with serum testosterone levels in boys from P1L to P5 (r = 0.76; P less than 0.001), while LH RIA levels did not (r = 0.18). Serum LH IRMA concentrations were above the prepubertal range (greater than 0.5 IU/L) in 67% of children with CPP (group average, 1.8 +/- 1.4 IU/L) and 87% of children with DP (1.6 +/- 1.4 IU/L).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Symptomatic cerebral swelling complicating diabetic ketoacidosis documented by intraventricular pressure monitoring: survival without neurologic sequela.

A six-year-old boy developed symptomatic cerebral swelling four hours after the initiation of treatment for newly diagnosed diabetes mellitus complicated by ketoacidosis. Ventriculostomy documented intracranial pressure over a two-day period. Increased intracranial pressure unresponsive to controlled hyperventilation and sedation was treated by administering a diuretic and by drainage via a ventriculostomy. Intracranial pressure monitoring was a useful adjunct in management of this rare, but often lethal, complication of diabetes mellitus. One year later, both school performance and the results of a neurologic examination were normal.

Brain Edema↗

A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism.

We describe a large, three generation kindred in which 16 individuals were affected with alopecia, hyposmia or anosmia, conductive deafness associated with protruding ears, microtia, and/or atresia of the external auditory canal, hypogonadotropic hypogonadism due to LH/FSH deficiency, and a greater than normal tendency to dental caries. Variable manifestations include mild facial asymmetry, mental retardation, congenital heart defect, and cleft palate. This seems to be a previously undescribed pleiotropic autosomal dominant trait with variable expressivity. The manifestations can be explained on the basis of involvement of the ectoderm and neuroectoderm of the first and second branchial arches, of Rathke's pouch, and of the diencephalon.

Abnormalities, Multiple↗

Doctor shopping with the child as proxy patient: a variant of child abuse.

Over a three-year period, we have seen in consultation four children whose mothers cited complaints referable to every organ system and which had persisted for many years. The parents had consulted a total of 99 physicians in eight states. Absence from school ranged from 40 to 200 days a year. Physical examinations of all patients and extensive and repeated laboratory studies were normal. On psychiatric examination the mothers exhibited paranoid thinking and a conviction of serious medical illness in their child which approached delusional proportions. They resisted psychiatric consultation and refused psychotherapy. The mother-child relationship was remarkably symbiotic, the two teen-age patients essentially voicing complaints which were indistinguishable from those reported by their mothers. The fathers invariably supported their wives' concerns. Subsequently, parents and children left treatment, continuing to "doctor shop." Long-standing multisystem complaints in a child with normal growth and maturation are incompatible with any known significant organic disease, but suggest a serious emotional problem within the family. Further, parents who take such children from doctor to doctor are frequently disturbed themselves and may use an offspring as a proxy patient. An accurate diagnosis depends on careful history-taking from parents, patient, health professionals, and schools.

Absenteeism↗

A dose-response curve for human growth hormone.

Although human GH (hGH) has been administered to GH-deficient patients for over 20 yr, there are minimal published data on the relationship of response to dose. We have given hGH on the basis of body weight to 93 prepubertal GH-deficient patients over an initial 12 months of therapy. Their annual growth rate while receiving hGH was 5.58 +/- 2.30 (+/- SD) cm at a dose of 30 mIU/kg, three times a week (tiw; n = 27); 7.31 +/- 1.75 (+/- SD) cm at a dose of 60 mIU/kg, tiw (n = 38); 7.22 +/- 3.12 (+/- SD) cm at a dose of 80 mIU/kg, tiw (n = 12); and 8.94 +/- 1.19 cm (+/- SD) at a dose of 100 mIU/kg, tiw (n = 16). Doubling the dose from 30 to 60 mIU increased the mean rate of growth 1.3 times, and increasing the 30 mIU dose by a factor of 3.3 increased the mean rate of growth 1.6 times. The response (y) as a function of the log-dose (x) is defined by the equation y = -3.12 + 5.80 log x. When the effect of hGH is expressed as the increase in growth rate while receiving therapy, the log-dose relationship is defined by the equation y = -6.09 + 5.67 log x. This dose-response curve provides data which are useful in choosing the best dose of hGH for an individual patient. It also allows a more accurate projection of the costs and benefits of hGH therapy.

Adolescent↗

Trisomy 14 mosaicism: case report and review.

Complete or partial trisomy 14 is compatible with life. However, in the former case, mosaicism is probably always present. A case of trisomy 14 mosaicism is reported. Comparisons are made with other trisomy 14, trisomy 14 mosaicism, and duplication 14q cases previously reported. As a group, they share some clinical manifestations. The phenotype consists of multiple congenital anomalies, including microcephaly, broad nose, wide mouth, high or cleft palate, micrognathia, congenital heart disease, intrauterine growth retardation, and mental retardation. The present patient also has asthma, eczema, and developmental asymmetry.

Abnormalities, Multiple↗

Intrauterine hyperparathyroidism. Postmortem findings in two cases.

Intrauterine hyperparathyroidism is a self-limited condition seen in the neonate born of a mother with poorly controlled hypoparathyroidism. In this report, we describe the histologic findings in bone and parathyroids in twin infants with this condition who died from other causes. The skeleton showed osteopenia with evidence of increased bone turnover and defective mineralization, and there was parathyroid gland hyperplasia of the water-clear cell type. One twin died at birth, and the histologic findings were indistinguishable from those of infantile primary hyperparathyroidism; but the second twin, dying at 3 months of age, demonstrated noticeable improvement in the bone and parathyroid abnormalities.

Diseases in Twins↗

Growth hormone deficiency, brain development, and intelligence.

Twenty-nine patients with growth hormone (GH) deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of growth retardation in early childhood, and no evidence of pituitary tumors or other direct pituitary trauma. Fourteen patients had evidence of multiple hormone deficiencies, 14 had isolated GH deficiency, and one patient questionable isolated GH deficiency. Psychometric testing showed a normal IQ distribution. The GH deficiency was not associated with deficiencies in specific mental abilities. Likewise, GH treatment in later childhood and adolescence did not seem to influence intelligence. Patients with multiple hormone deficiencies had somewhat lower IQs than patients with isolated GH deficiency when socioeconomic status was controlled. We conclude that GH deficiency itself does not seem to affect human brain development and intelligence.

Adolescent↗

Collaborative study of the effects of human growth hormone in growth hormone deficiency. V. Treatment with growth hormone administered once a week.

Twenty-two GH-deficient patients received 6 IU GH weekly for 6 months. They increased their growth rate from 1.0 +/- 0.2 to 2.9 +/- 0.3 (SE) cm/6 months (P less than 0.01). However, their rate of growth was significantly less (P less than 0.05) than the rate [4.1 +/- 0.5 (SE) cm/6 months] observed earlier when they had received 2 IU GH three times a week. Seven patients received weekly GH for 18 months and they also grew significantly less (P less than 0.01) than when they had received GH divided over the week. These results suggest that once a week GH does not provide the most effective therapy for GH deficiency.

Drug Administration Schedule↗