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Biomedical subjects

P G Brosnan

Publications and source records attributed to P G Brosnan.

9 recordsLinked to original sources
PubMed2001

The hypothalamic pituitary axis in the fetus and newborn.

Glucocorticoid receptor activation in the fetal lung triggers maturation necessary for extra-uterine life. Antenatal treatment with betamethasone and dexamethasone has lowered severity of respiratory distress in very low birth weight infants, and dexamethasone given postnatally has resulted in short-term improvement in chronic lung disease. Recently, however, surfactant therapy has diminished the differential benefit of antenatal glucocorticoid treatment, and it has been difficult to show that postnatal dexamethasone therapy improves survival. Treated infants may have reduced weight gain, adrenal suppression, increased incidence of intestinal perforation and infection, and long-term developmental and metabolic problems. Recent data suggest that the fetal hypothalamic/pituitary/adrenal axis is active early and is precisely structured for an intricate sequence of specifically fetal developmental events, which may be deranged by dexamethasone therapy. We consider data suggesting that persistence of the fetal pattern in some premature infants constitutes adrenal insufficiency, and that therapy at stress replacement doses with less potent glucocorticoids might avoid side effects seen with traditional regimens.

Adrenal Cortex Hormones↗
PubMed2001

Ingested IFN-alpha preserves residual beta cell function in type 1 diabetes.

Type 1 diabetes mellitus is a chronic disorder that presumably results from an autoimmune destruction of the insulin-producing pancreatic beta cells. The therapeutic potential of interventions aimed at preventing type 1 diabetes can be assessed in newly diagnosed patients. Because there is a historical experience of a low incidence of spontaneous remission in type 1 diabetes mellitus, interventions preserving beta cell function have been used to identify positive therapeutic outcomes. We treated 10 newly diagnosed type 1 diabetes patients with 30,000 IU ingested interferon-alpha (IFN-alpha) within 1 month of diagnosis and examined the difference between baseline and Sustacal-induced (Mead Johnson Nutritionals, Evansville, IN) C-peptide responses, respectively, at 0, 3, 6, 9, and 12 months. Eight of the ten patients showed preserved beta cell function, with at least a 30% increase in stimulated C-peptide levels at 0, 3, 6, 9, and 12 months after initiation of treatment. There was no discernible chemical or clinical toxicity associated with ingested IFN-alpha. Our results support the potential of ingested IFN-alpha to preserve residual beta cell function in recent onset type 1 diabetes mellitus and the testing of IFN-alpha in a placebo-controlled trial.

Administration, Oral↗
PubMed1999

Effect of newborn screening for congenital adrenal hyperplasia.

OBJECTIVE: To compare the incidence of diagnosis and morbidity in newborns who were screened with newborns who were not screened for congenital adrenal hyperplasia (CAH). DESIGN: A retrospective cohort study. SETTING: Arkansas, Oklahoma, and Texas. PATIENTS: An unscreened population in Arkansas and Oklahoma (n = 400118) was compared with a screened population in Texas (n = 1613378) during a 5-year period. Simultaneous data were collected on the incidence of diagnosis and associated morbidity in patients with CAH. MAIN OUTCOME MEASURES: Diagnosis of CAH, age (in days) at diagnosis, and frequency and length of initial hospitalization. RESULTS: The incidence of diagnosis of classic CAH per 100000 newborns in the unscreened cohort (5.75) and in the screened cohort (6.26) was similar (relative risk, 0.92; 95% confidence interval, 0.58-1.44). The unscreened group had 0.73 fewer male newborns with salt-wasting CAH diagnosed per 100000 newborns (relative risk, 0.73; 95% confidence interval, 0.35-1.56). The median age at diagnosis was 26 days for male newborns with salt-wasting CAH in the unscreened cohort vs 12 days in the screened cohort (z = 2.49; P = .01). Male newborns with simple-virilizing CAH and newborns with nonclassic CAH were detected only in the screened cohort. CONCLUSIONS: There was not a statistically significant (P = .73) increase in the diagnosis of salt-wasting CAH in the screened cohort. Male newborns benefited as a result of significantly (P = .01) earlier diagnosis, reduced morbidity, and shorter lengths of hospitalization. Large collaborative studies or meta-analyses are needed to determine the life-saving benefits of screening.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Human chorionic gonadotropin testing. Changing testicular response in infants with microphallus and gonadotropin deficiency.

The evaluation of microphallus often includes human chorionic gonadotropin (HCG) stimulation to evaluate testicular androgen production. The response in testosterone secretion after five days of stimulation with chorionic gonadotropin is abnormal in patients with either primary testicular defects or gonadotropin deficiency. The testes of gonadotropin-deficient children do respond if the chorionic gonadotropin therapy is continued for six weeks. The current study reports a normal response to the short course (five days) of chorionic gonadotropin therapy in two 2-month-old patients with XY chromosomes with microphallus whose clinical course and repeated testing at age 3 or 4 years indicated gonadotropin deficiency. The normal response in the neonatal period is probably the result of maternal chorionic gonadotropin priming of the fetal testes in utero. These results indicate that HCG testing is an unreliable method for identifying gonadotropin deficiency in the neonatal period.

Abnormalities, Multiple↗
PubMed1984

The somatomedin-C receptor of human placenta.

The binding and physical characteristics of the human placenta somatomedin-C (Sm-C) receptor were investigated and compared with those of the placental insulin receptor. These receptors were found to have many similar properties, but several distinctions exist between them. The two receptors have similar binding properties. Although distinct receptors, as evidenced by specificity studies, the Sm-C and insulin receptors possess similar affinities (10 X 10(9) L/mol and 3 X 10(9) L/mol, respectively) and receptor concentrations (0.4 pm/mg and 0.2 pm/mg) in placental membranes. There is also a low-affinity, high-capacity receptor for each hormone. The intact receptors are indistinguishable in size by three methods. The Stokes radius is 7.2 nm by gel filtration, the sedimentation coefficient is 11S, and the SDS polyacrylamide gel apparent molecular weight is approximately 350,000 daltons. The two receptors differ in their pH optimum for ligand binding, their isoelectric points, and their subunit size. The pH optimum for Sm-C binding is 8.2, and for insulin binding the optimum is 7.9. The isoelectric point for the Sm-C receptor is 4.6, whereas the isoelectric point for the insulin receptor is 4.2. Although the whole receptor and the half receptors for Sm-C and insulin cannot be distinguished by size on SDS gels, the binding subunit for the Sm-C receptor appears to be 8000 daltons smaller than that of the insulin receptor (134,000 v 142,000 daltons). We conclude from these studies that the insulin and Sm-C receptors of human placenta are similar in structure but are distinct entities.

Animals↗
PubMed1980

A new familial syndrome of 46,XY gonadal dysgenesis with anomalies of ectodermal and mesodermal structures.

Two 46,XY phenotypic female siblings, aged 1 1/2 and 8 1/2 years, have peculiar facies, cardiac, renal, musculoskeletal, and ectodermal anomalies, short stature, streak gonads, and mild developmental delay. Previous reported cases of 46,XY gonadal dysgenesis have not had major associated malformations. These children present a new constellation of anomalies unlike those seen in other types of gonadal dysgenesis and represent a new familial syndrome of 46,XY gonadal dysgenesis.

Abnormalities, Multiple↗
PubMedDate not supplied

Hypothalamic-pituitary dysfunction associated with Moyamoya disease in children.

Moyamoya disease is a rare cerebral vascular disease that results in narrowing of the vessels of the circle of Willis and the formation of a network of collateral vessels at the base of the brain for compensatory perfusion. Moyamoya disease has the highest incidence during the first decade of life, and children present most frequently with transient ischemic attacks. We present two cases of Moyamoya disease in children with associated hypothalamic-pituitary dysfunction. Both children presented to the endocrinologist for decreased growth velocity. One child had hypothyroidism and both had growth hormone deficiency. A review of the literature reveals a few isolated case reports of hypothalamic-pituitary dysfunction occurring with Moyamoya disease and with other states of cerebral vascular insufficiency. We suggest that children with compromise of cerebral vascular perfusion be monitored closely for clinical signs and symptoms of hypothalamic-pituitary dysfunction.

Carotid Arteries↗
PubMedDate not supplied

Methodological issues in newborn screening evaluation with special reference to congenital adrenal hyperplasia.

Evidence-based evaluation of newborn screening is essential because of the increasing number of genetic tests, the mandatory nature of newborn screening in the United States, and the growing cost to the public to maintain expensive screening programs. This paper discusses the methodological problems that arise when applying universally accepted criteria to disorders such as congenital adrenal hyperplasia. These problems include the tendency of screening to alter the natural history of the disease, the lack of consensus about terms and definitions, and the paucity of longitudinal studies on screen detected neonates. In order to evaluate and compare candidate screens we recommend formal national trials of promising programs, with defined responsibility of state agencies, physicians, patients, and insurers for data submission and analysis.

Adrenal Hyperplasia, Congenital↗