Biomedical subjects

C Rodd

Publications and source records attributed to C Rodd.

15 recordsLinked to original sources

PubMed2004

Action of estradiol on epiphyseal growth plate chondrocytes.

Estrogen plays an important role in the human growth plate by accelerating growth and promoting epiphyseal fusion in both sexes. Nevertheless, the precise mechanisms responsible for these effects are poorly understood. In the present study, we examined the role of 17beta-estradiol (E2) on cell proliferation and viability, type X collagen synthesis, alkaline phosphatase activity, and matrix calcification in primary cultures of resting, proliferating, and prehypertrophic chondrocytes derived from explants of the bovine fetal epiphyseal growth plate. Growth plate chondrocytes were isolated and separated into maturationally distinct subpopulations, which were cultured for 7-21 days to high density in either (1) serum-free medium, (2) 1 nM thyroid hormone (T3), (3) E2 concentrations ranging from 10(-13) M to 10(-7) M, or (4) a combination of T3 and E2. To compare E2 effects in both sexes, chondrocytes were harvested from 8 fetuses of both sexes. After hormone treatment, cell cultures were analyzed for cell number and viability, collagen type X, alkaline phosphatase (ALP), and matrix calcification. Neither DNA content nor cell viability were affected by the duration or type of hormone treatment. By itself, E2 stimulated maturation of all subpopulations only in pharmacologic doses (10(-7) M). Physiologic E2 concentrations were no different than negative controls treated with ITS (insulin, transferrin, and selenite). Regardless of E2 concentrations, the addition of E2 to 1 nM T3 did not appreciably affect the response to T3 alone, which stimulates maturation of the phenotype. All effects were comparable in both male and female chondrocytes, in all cell subpopulations (maturation stages) and fetuses of varying gestational age. These findings indicate that at physiologic concentrations, the effects of E2 on fetal bovine growth plate chondrocyte appear to be indirect and independent of T3, suggesting that, in vivo, E2 acts in concert with other factors or hormones to induce fusion of the growth plate.

Alkaline Phosphatase↗

PubMed2004

Megestrol acetate promotes euglycemia and appetite in a child with persistent hyperinsulinemic hypoglycemia of infancy.

UNLABELLED: This report describes a successful treatment with megestrol acetate in a child with persistent hyperinsulinemic hypoglycemia of infancy (PHHI). An 8-y-old child with PHHI treated with octreotide had marked impairment of appetite sensation and feeding skills. Within 3 wk of starting megestrol acetate (8 mg/kg/d) to stimulate her appetite, she had a significant improvement. By 1 y postinitiation, she had acquired age-appropriate eating habits. The megestrol acetate caused hyperglycemia, necessitating the discontinuation of all other therapy for her hypoglycemia. Her height growth remained normal but she was found to have asymptomatic adrenal suppression. CONCLUSION: Megestrol acetate appeared to stimulate appetite and regulate glucose homeostasis in this child with PHHI. Additional studies will be required to document its efficacy and safety in other children with this disorder.

Appetite↗

PubMed2001

Multinodular goiter in children.

OBJECTIVE: As multinodular goiter (MNG) is an uncommon pediatric disorder, we decided to evaluate the children with this diagnosis at our center to try to delineate better its etiology, the risk of malignancy and appropriate management strategies. METHODS AND RESULTS: Eighteen patients (12 girls and 6 boys) were the subject of this retrospective review spanning a period of 20 years. All were previously well, except one, and none had had head or neck irradiation. Average age at diagnosis was 12.8 years. Four children belonged to two previously identified kindreds diagnosed with familial MNG. These families had members affected with multiple cases of non-medullary thyroid carcinoma (NMTC). All were euthyroid and had no symptoms. In eight of 18 patients, the clinical examination missed the presence of multiple nodules which were subsequently detected by ultrasound. Twelve patients had tissue diagnosis by fine needle aspirate cytology (FNAC) or surgery. Five of eight patients undergoing surgery had nodular hyperplasia, one had a follicular adenoma and one had a normal thyroid gland on histology. There was one patient with papillary carcinoma combined with nodular hyperplasia. Seven of the patients had evidence of antithyroid autoimmunity. CONCLUSION: The etiology of pediatric MNG appears multifactorial including autoimmune and familial factors. We believe that previously healthy children can usually be managed conservatively. Ultrasound at the time of diagnosis and in follow up seems beneficial. Familial forms appear to warrant close follow up, given the apparent increased risk of malignancy. The risk of malignancy while low remains real.

Adenoma↗

PubMed2001

Bisphosphonates in dialysis and transplantation patients: efficacy and safety issues.

Bisphosphonates are an old class of compounds. They were used in the 1930s as antiscaling and anticorrosion agents in washing powders and water to prevent the deposition of calcium crystals. Those basic functions were later utilized in an attempt to prevent ectopic calcifications in humans. The early studies demonstrated that bisphosphonates had a strong affinity for bone. That property was first exploited when the compounds were used for "bone scans." Currently, the drugs are used for treatment of hypercalcemic conditions, abnormal bone remodelling, Paget disease, malignancy, and osteoporosis. Bisphosphonates have several important toxicities: acute renal failure, worsening renal function, reduced bone mineralization, and osteomalacia. For those reasons and others, this class of drugs has not yet been approved for use in children or in patients with severe renal insufficiency. The present review covers several aspects of bisphosphonates: molecular structure, routes of administration, pharmacology, mechanisms of action, toxicities, and exceptional uses in children with renal disease.

Bone Density↗

PubMed2000

Multicompartment urea kinetics in well-dialyzed children.

BACKGROUND: We have reported catch-up growth with hemodialysis (HD) of approximately 15 hours/week. Without an equilibrated post-treatment blood urea nitrogen, the variable-volume single-pool (VVSP) model will not account for urea rebound, inflating the estimated HD dose (K(d)t/V). A two-pool model (FVDP) predicts rebound, but requires fixed compartment volumes for the equations to be solvable in closed form, also inflating K(d)t/V. METHODS: We developed an approximate perturbation solution (WKB method) to a variable volume, two-pool (VVDP) model. Estimated model parameters were compared with the results of equilibrated kinetic studies using measured clearance K(d) (N = 17). Once the model was validated, we re-analyzed 292 kinetic studies from our earlier cohort, which was considered well-dialyzed on the basis of growth rates (N = 12, mean annual change in height standard deviation score +0.31, mean follow-up of 26 months). RESULTS: For the VVSP, FVDP, and VVDP models, respectively, the mean errors were (1) K(d)t/V, 0.22 +/- 0.07, 0.29 +/- 0.17, 0.06 +/- 0.07 (ANOVA, P < 0.001); (2) urea distribution volume vol/wt (%), -8.2 +/- 4.2, -9.1 +/- 3.0, -2.2 +/- 3.6 (P < 0.001). Sequential studies confirmed reproducibility, with a coefficient of variation < or = 5%. In the earlier cohort, a comparison of the VVSP and VVDP models yielded the following: (1) K(d)t/V, 1.91 +/- 0.35 vs. 1.76 +/- 0.33 (P < 0.001); (2) normalized protein catabolic rate (nPCR, g/kg/day), 1.56 +/- 0.39 vs. 1.52 +/- 0.38 (P < 0.001); and (3) K(d) (whole blood, mL/kg/min), 4.8 +/- 0.9 vs. 4.4 +/- 0.8 (P < 0.001). CONCLUSION: This VVDP model yields reliable estimates of K(d)t/V and other kinetic parameters using standard blood urea nitrogen sampling. Analysis of patients previously characterized as well-dialyzed on the basis of growth rates clarifies the HD dose needed to sustain normal growth.

Adolescent↗

PubMed1999

Hypercalcemia of the newborn: etiology, evaluation, and management.

Hypercalcemia in infants is uncommon but has potentially serious sequelae. This review examines four cases of neonatal hypercalcemia, emphasizing appropriate investigations and treatment of acute and chronic hypercalcemia. The paper provides additional information as to the mechanisms of calcium dysregulation in idiopathic infantile hypercalcemia, Williams syndrome, vitamin D intoxication, and parathyroid and parathyroid-related protein disturbances.

Female↗

PubMed1999

Growth during maintenance hemodialysis: impact of enhanced nutrition and clearance.

Growth of children during maintenance hemodialysis has been reported to be uniformly poor, with a mean annual loss of 0.4 to 0.8 SD in height. We adopted an intensive program of closely monitored energy and protein intake with dialysis urea clearances exceeding conventional recommendations. Twelve prepubertal or early pubertal children (aged 7 months to 14 years) were monitored for an average of 2.2 years (range 4 to 81 months) while receiving maintenance hemodialysis. These children received an average of 90.6% and 155.9% of their recommended energy and protein nutritional intake, respectively. With a prescribed urea clearance of 5 mL/kg/min, we achieved a mean single treatment urea clearance normalized for total body water of 2.00, a urea reduction ratio of 84.7%, and an average time of hemodialysis of 14.8 h/wk, all well beyond current guidelines. Over the course of dialysis treatment, the improvement in height SD score was+0.31 SD/y (+0.32 excluding the 2 children treated with recombinant human growth hormone). Normal growth was achieved without overt obesity and was associated with normal pubertal growth spurt. These findings suggest that the combination of increased dialysis and adequate nutrition can promote normal growth in children treated with long-term hemodialysis.

Adolescent↗

PubMed1999

Moderate renal failure in association with prolonged acquired hypothyroidism in children.

We evaluated five children with prolonged primary hypothyroidism and noted a significant reduction in renal function (40%), which was reversible with hormonal replacement. This decline was higher than reported in adults and was of sufficient magnitude to warrant altering drug-dosing schedules. Furthermore, patients with moderately reduced renal function should be carefully evaluated for signs and symptoms of hypothyroidism.

Adolescent↗

PubMed1999

A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations.

Permanent primary congenital hypothyroidism (CH) can be caused by abnormal thyroid differentiation (athyreosis), migration (ectopy), or function (leading to goiter). Goiters follow an autosomal recessive pattern of inheritance, whereas ectopy and athyreosis are considered as a single sporadic entity with a female preponderance. On the other hand, a high prevalence of extrathyroidal malformations has been reported in CH, but without linking specific defects to specific types of CH. On the basis of TSH screening, 273 newborns were referred to an academic pediatric endocrinology clinic in the province of Quebec between 1988 and 1997. Of 230 patients with permanent primary CH who had scintigraphy at diagnosis, 141 had ectopy (104 girls), 36 had athyreosis (21 girls), 42 had goiter (18 girls), 10 (3 girls) had a normal scan, and 1 girl had hemiagenesis. Only in the ectopies was the proportion of girls significantly higher than 0.5 (P<0.001). Isolated cardiac malformations were observed in 7 patients (3.0%), a prevalence 5-fold higher than that in the general population; this was largely due to atrial and ventricular septal defects, which were only observed in ectopy and athyreosis. Our data suggest that the molecular mechanisms that lead to complete absence of thyroid differentiation or defective thyroid migration 1) may be similar, but are modulated by the genetic makeup of the embryo and/or the hormonal milieu of the fetus; and 2) may also be involved in septation of the embryonic heart.

Abnormalities, Multiple↗

PubMed1998

The use of pamidronate in three children with renal disease.

The successful use of pamidronate, a bisphosphonate, for the treatment of hypercalcemia and/or osteopenia is reported in three children with renal failure or following renal transplant. Patient 1 was an 11-year-old post renal transplant male who received a single dose of i.v. pamidronate (0.5 mg/kg) for the treatment of acute hypercalcemia associated with a pathological fracture and subsequent immobilization. Prompt resolution of the hypercalcemia was seen. He received a second course of pamidronate (0.5 mg/kg per day for 3 days) for the treatment of osteopenia and has had a subsequent 15% increase in lumbar spine bone mineral content (BMC). Patient 2, a 14-year-old male on peritoneal dialysis, presented with symptomatic hypercalcemia associated with tertiary hyperparathyroidism. A single dose of i.v. pamidronate (0.4 mg/kg) was given with prompt resolution and prolonged control of his hypercalcemia. The third patient was a 16-year-old female, also in renal failure on peritoneal dialysis. Her course had been complicated by marked osteopenia. I.v. pamidronate (0.5 mg/kg per dose) was given on 3 successive days before and after renal transplant in an attempt to stabilize her bone mineral density (BMD) around the time of renal transplantation, when additional glucocorticoid was necessary. Her total body BMC and BMD remained stable pre and post transplant. The treatment was effective and well tolerated in all three patients. Hence pamidronate is safe and effective for the management of hypercalcemia and osteopenia in children with renal failure and/or renal transplant.

Adolescent↗

PubMed1998

Cystic thyroid lesions in children.

BACKGROUND/PURPOSE: Cystic lesions of the thyroid encompass a wide and heterogeneous group of disease states in children, ranging from benign purely cystic entities to malignant tumors. The purpose of this study was to study both the presentation and management of cystic thyroid lesions in the pediatric population. METHODS: A retrospective review of all thyroid masses presenting between 1978 and 1996 and found to be purely or partially cystic on ultrasound examination was conducted, looking at presentation, family history, laboratory values, ultrasound scan and radionuclide imaging, and pathological and cytological evaluation. RESULTS: Twenty-four patients (19 girls, 5 boys) aged 6 to 18 years received the diagnosis of cystic lesions of the thyroid. Of these, 23 presented with painless neck masses, 21 were clinically euthyroid, only one had a single abnormal thyroid function test, only two had mildly positive antithyroid antibody test results, and nearly 30% had a positive family history of thyroid disease. Ultrasonography showed pure cysts in five patients and mixed solid cystic lesions in 19 patients. On scintiscan, six lesions were hot, 13 were cold, three showed normal uptake, and two were mixed. Treatment included either observation, aspiration, cyst sclerosis, surgery, or combinations thereof. Pathological and cytological results included follicular adenoma (n = 9), cystic degeneration (n = 6), multinodular goiter (n = 4), carcinoma (n = 2), branchial cleft cyst (n = 1), and undetermined (n = 2). CONCLUSIONS: Thyroid cysts are often thought to represent benign degenerative disease. Our study, which is the first in the literature to specifically address thyroid cysts in children, shows that ultrasound scan is useful in evaluating thyroid masses, whereas laboratory and radionuclide are of less value, and that single lesions of mixed echogeneity are likely to represent neoplasms, a significant percentage of which are malignant.

Adolescent↗

PubMed1997

Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor.

Activating somatic mutations in the thyrotropin (TSH) receptor have been identified as a cause of hyperfunctioning thyroid adenomas, and germline mutations have been found in familial nonautoimmune hyperthyroidism and sporadic congenital hyperthyroidism. All mutations reported to date have been located in the transmembrane domain. We now report an example of an activating mutation in the extracellular, TSH-binding domain, found in a male infant with congenital hyperthyroidism due to a toxic adenoma. The pregnancy was remarkable for fetal tachycardia. Scintigraphic studies demonstrated a large nodule in the right lobe, and a hemithyroidectomy was performed at the age of 2 yr. Direct sequencing of the TSH receptor gene revealed a mutation in one allele resulting in a substitution of serine281 by isoleucine (Ser281--> Ile) in the extracellular domain. The mutation was restricted to the adenomatous tissue. Expression of the Ser281--> Ile mutation in vitro revealed an increase in basal cAMP levels. Affinity for TSH was increased by the mutation. These findings demonstrate that activating mutations can also occur in the extracellular domain of the TSH receptor, and support a model in which the extracellular domain serves to restrain receptor function in the absence of TSH or antibody-induced conformational changes.

Adenoma↗

PubMed1992

Prediagnostic malakoplakia presenting as a chronic inflammatory mass in the soft tissues of the neck.

Malakoplakia presenting in the head and neck is very rare. We present a case of an inflammatory mass in the neck, clinically mimicking actinomycosis in a 67-year-old man. Repeated culture of E. coli and histological and electron microscopic examination of biopsy material showed an infiltration of granular macrophages and intracellular gram negative bacilli, but no classical Michaelis-Gutmann bodies. The clinical and pathological findings and criteria for the diagnosis of malakoplakia are discussed.

Aged↗

PubMed1992

Ontogeny of hepatic nuclear triiodothyronine receptor isoforms in the rat.

We have determined the contribution of the thyroid hormone receptor (TR) isoforms TR alpha 1 and TR beta 1 to the postnatal rise in rat hepatic nuclear T3-binding capacity. In agreement with previous studies, total hepatic nuclear binding capacity rose by about 8-fold from the 19th day of gestation to young adulthood at 2 months of age (0.10 +/- 0.03 to 0.86 +/- 0.17 pmol/mg DNA). The levels of specific TR species were measured by immunoprecipitation of T3-binding activity from hepatic extracts using a panel of antisera directed against specific regions of the TR isoforms. The difference between receptor immunoprecipitated with antibody against TR beta 1 and that precipitated with an antibody against an identical region in both TR beta 1 and TR alpha 1 was tentatively assumed to represent TR alpha 1. TR alpha 1 accounted for virtually all T3-binding activity in fetal liver on gestational day 19 (G19), increased by 2-fold shortly after birth, and remained constant thereafter. TR alpha 1 mRNA, on the other hand, was highest in concentration on G16 and fell by 50-75% in the adult. TR beta 1 was undetectable by immunoprecipitation of hepatic extracts from fetuses on G19. However, Northern analysis showed the presence of TR beta 1 mRNA in the fetal liver, which rose in concentration by 3- to 4-fold in late gestation and then remained constant. The contribution of TR beta 1 to total binding capacity rose to 33% and 40% on postnatal days 15 and 30, respectively, and to 80% in the adult liver. Immunohistochemical analyses of hepatic sections confirmed the presence of very low levels of TR beta 1 in fetal liver as early as G16 and G19, and a sharp rise in TR beta 1 protein concentration in the postnatal period. This indicated that the increase in TR beta 1-binding capacity results from increased TR beta 1 mass. The increase in TR beta 1-binding capacity, thus, is due to increased translational efficiency of the beta 1 mRNA or stabilization of the TR beta 1 protein. The prominence of TR alpha 1 in both rat fetal liver and fetal brain, as previously demonstrated in our laboratory, raises the possibility that this receptor isoform may carry out specialized functions in the fetus and that TR beta 1 subserves still other functions at later stages of development.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMedDate not supplied

Thyroid abnormalities as a feature of DiGeorge syndrome: a patient report and review of the literature.

DiGeorge syndrome or anomaly consists of a developmental field defect which is characterized by congenital absence or hypoplasia of the thymus and parathyroids, as well as facial dysmorphism and congenital heart defects. Other congenital malformations may coexist, in particular, thyroid abnormalities. A case of congenital hypothyroidism and DiGeorge syndrome is reviewed. Necropsy, clinical, and experimental studies also show that thyroid abnormalities may be a feature of DiGeorge syndrome. Although this could be purely coincidental, our case suggests that thyroid gland dysgenesis may be more common than previously thought. Thus, children with the DiGeorge syndrome may be at higher risk for hypothyroidism. Because of this potential association, patients who are considered to have this anomaly should have early newborn thyroid screening.

Adult↗