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Biomedical subjects

M MacGillivray

Publications and source records attributed to M MacGillivray.

12 recordsLinked to original sources
PubMed2001

Linear growth characteristics of congenitally GH-deficient infants from birth to one year of age.

Birth length has been reported to be either normal or reduced in infants with congenital GH deficiency (CGHD). We evaluated 46 infants with CGHD followed in a single regional medical center. All were born full term and had peak GH of less than 10 microg/liter after provocative stimulation. Length SD score at birth was normal but subsequently showed deceleration, at 6 months and 12 months of age, before GH treatment. The majority were delivered vaginally (83%), and delivery was uncomplicated in 61%. Four patients (9%) had breech vaginal delivery. Perinatal morbidities were found in 72% of infants and included jaundice (n = 17), hypoglycemia with or without seizure (n = 14), and hypoxemia (n = 5). Multiple pituitary hormone deficiencies were found in 85% of the subjects. Organic lesions were documented in all 22 subjects who had magnetic resonance imaging and in 4 of 11 subjects who had computed tomography scan. Only the hypoglycemic infants received early GH treatment. Growth data in hypoglycemic and normoglycemic CGHD infants were not significantly different. In our population, CGHD did not adversely affect fetal growth but is essential for normal linear growth during early infancy. Congenital developmental abnormalities in the hypothalamic-pituitary region are the most common cause of CGHD and are best diagnosed by an magnetic resonance imaging study.

Aging↗
PubMed1996

Physician and clinic charges for diagnosing growth hormone deficiency.

Physician and clinic charges for diagnosing growth hormone deficiency (GHD) in children are not generally known, whereas the charges for purchasing growth hormone (GH) are known. We recently surveyed the charges submitted to third-party payers for diagnosing GHD in five pediatric endocrine clinics throughout the United States: the Albert Einstein College of Medicine, Baylor College of Medicine, Health Science Schools of the State University of New York at Buffalo, Oregon Health Sciences University, and the University of Chicago. The financial data analyzed included charges for physician services and for GH testing. Different approaches to the medical examination of children with suspected GHD at these clinics prevented any comparison of physician or GH testing charges. However, the charges for diagnosing GHD could be determined for each pediatric endocrine clinic if the methods of examination were not considered. Contractual adjustments, net revenues, costs, and net margins were not surveyed. Subjective comments from the study sites suggest significantly reduced reimbursement amounts. We conclude that the total charges for diagnosing GHD submitted to third-party payers at these institutions averaged $1719.

Child↗
PubMed1995

Characterization of a low molecular mass form of insulin-like growth factor binding protein-3 (17.7 kilodaltons) in urine and serum from healthy children and growth hormone (GH)-deficient patients: relationship with GH therapy.

The insulin-like growth factor binding proteins (IGFBPs) are the carriers for insulin-like growth factor (IGF0-I and IGF-II. IGFBP-3 is GH-dependent and circulates associated with IGFs and an acid-labile subunit to form a 150-kilodalton (kDa) complex. In human serum, two immunoreactive molecular weight forms of IGFBP-3 have been identified. In human urine, radioimmunoassayable levels of IGFBP-3 have been detected. The objectives of this study were to characterize the molecular weight forms of IGFBP-3 in urine and serum of healthy children and adults and in children with GH deficiency (GHD), to quantify the urinary molecular weight forms of IGFBP-3, and to evaluate the relationship of these forms with GH therapy. Urine and serum were obtained from 12 prepubertal children with GHD, before and after 6 months of GH therapy, from 30 prepubertal healthy children, and from 8 healthy adults. Western immunoblotting (WIB) with IGFBP-3 antiserum (alpha IG-FBP-3g1) showed that in urine the most representative IGFBP-3 was a 17.7-kDa form. The 17.7-kDa IGFBP-3 was high in urine of healthy children compared with healthy adults and was low in children with GHD but increased after GH therapy. Urinary IGFBP-3 immunoreactive profile was determined by neutral-size exclusion chromatography, followed by IGFBP-3 RIA analysis of the fractions. Urine showed a major peak of IGFBP-3 immunoreactivity around 17 kDa. The 17-kDa urinary IGFBP-3 chromatographic peak averaged 8461 +/- 367 ng/12 h.m2 of body surface in healthy children, 3415 +/- 739 in adults (P < 0.001), 2294 +/- 354 in children with GHD before GH therapy (P < 0.001), and 7940 +/- 1874 in children with GHD after GH therapy. Urinary IGFBP-3 was also measured by RIA in unfractionated urine; healthy children showed levels significantly higher (14575 +/- 460 ng/12 h.m2) than adults (7823 +/- 1083, P < 0.001) and higher than children with GHD before GH therapy (4710 +/- 703, P < 0.001). Again, however, immunoreactive IGFBP-3 increased after GH treatment (12294 +/- 3394). In the serum of the healthy children we characterized by specific IGFBP-3 WIB analysis, a 17.7-kDa immunoreactive form of IGFBP-3 that was absent in the serum of healthy adults and low in patients with GHD, increased during GH therapy. Serum samples were subjected to neutral-size exclusion chromatography and the fractions were analyzed by WIB.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Urinary insulin-like growth factors (IGF) and IGF-binding proteins in normal subjects, growth hormone deficiency, and renal disease.

Recent studies in our laboratories have shown that urine from healthy adults contains immunoreactive and intact insulin-like growth factor-binding protein-3 (IGFBP-3). The aim of this study was to assess urinary IGF-I, IGF-II, and IGFBP-3 in a cross-sectional study of healthy subjects, as well as characterize urinary IGFBPs (uIGFBps) in patients with GH deficiency (GHD) and renal disease, such as, Alport syndrome, immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and systemic lupus erythematosus. Urinary concentrations of IGF-I and IGF-II in pooled spot morning urines of healthy subjects, measured by RIA, were low and relatively unaltered throughout age, when expressed as either nanograms per milliliter or nanograms per milligram creatinine. To determine the complement of IGFBPs in urine of healthy subjects, spot morning urine samples were subjected to Western ligand blot and immunoblot analysis. IGFBP-3 was detected at 40-50 kDa, possibly due to variable glycosylation of uIGFBP-3. In addition, a 32-kDa IGFBP-2 and smaller unclassified IGFBPs were detected. Unlike uIGFs, urinary concentrations of IGFBP-3 (uIGFBP-3; nanograms per milligram creatinine) were age-, but not sex-related. Levels of uIGFBP-3 ranged from 40-60 ng/mL in children between 4 and 10 yr of age. After 11 yr, immunoreactive uIGFBP-3 progressively declined, attaining a plateau after 26 yr of age to approximately 18 ng/mg creatinine. uIGFBP-3 did not correlate with uIGF levels. Regulation of IGFBP-3 in the urine of normal subjects and of renal disorders was examined by RIA, Western ligand blot (WLB), and protease assay. Intact uIGFBP-3 was consistently found in normal urine and little urinary protease was identified. In GHD patients, IGFBP-3 by WLB was low or undetectable, whereas RIA levels of uIGFBP-3 were normal or high, consistent with the presence of IGFBP-3 proteolytic activity. In Alport syndrome, both RIA measures and WLB analysis were high, as was the IGFBP-3 proteolytic activity. Patients with immunoglobulin A nephropathy, focal segmental glomerulosclerosis and systemic lupus erythematosus measured low-normal levels of IGFBP-3 by WLB and RIA, and displayed little protease activity. This study provides normative data concerning radioimmunoassayable levels of IGFBP-3 in urine. The presence of normal-elevated levels of uIGFBP-3 by RIA in GHD indicates that uIGFBP-3 levels are not under GH control and are unlikely to represent filtered serum IGFBP-3.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

3 alpha-androstanediol glucuronide in virilizing congenital adrenal hyperplasia: a useful serum metabolic marker of integrated adrenal androgen secretion.

To determine whether serum 3 alpha-androstanediol glucuronide (3AG) reflects the overall effect of integrated adrenal androgen secretion in the virilizing form of congenital adrenal hyperplasia (CVAH), circadian levels (0800, 1200, 1600, and 2000 h) of serum 3AG and 17-hydroxyprogesterone (17OHP) or 11-deoxycortisol (S), androstenedione (A), testosterone (T), and 24-h urinary 17-ketosteroids (17KS) were examined in seven patients (pts) with classical 21-hydroxylase deficiency (21OHD) and one pt with classical 11 beta-hydroxylase deficiency (11 beta OHD). Hormonal studies were conducted during the second day of dexamethasone (Dex) administration (2 mg/day). In five poorly controlled CVAH pts, including the 11 beta OHD pt, highly elevated baseline morning (AM) serum 17OHP or S as well as A levels, and elevated AM T levels in three pts decreased markedly in the evening (PM), while elevated serum 3AG showed no significant circadian changes; 17KS levels were markedly elevated for age. During Dex, moderately or slightly elevated AM 17OHP, A, or T in two to four pts with 21OHD decreased to the normal range in the PM. In the pt with 11 beta OHD, S, A, and T levels were suppressed. 3AG levels were modestly elevated or normal, without circadian changes, in these pts; 17KS levels were elevated or normal. In two other 21OHD pts, modestly elevated AM baseline 17OHP and A levels decreased in the PM; elevated AM T decreased in one pt in the PM; modestly elevated 3AG levels showed no circadian changes; 17KS levels were modestly elevated. During Dex, normal or slightly elevated serum steroids and 17KS levels were associated with normal or high normal 3AG levels without circadian changes. In one postpubertal female with 21OHD, modestly elevated AM baseline 17OHP levels decreased at 2000 h; normal A and T levels throughout the day and low normal 17KS were associated with slightly low 3AG levels, without circadian variation. During Dex treatment, normal 17OHP, A, T, and low 17KS levels were associated with low 3AG levels without circadian variation. In all pts as a group, an excellent correlation (r = 0.9) was found between either 0800 h or mean, or 2000 h serum 3AG levels and 17KS. In addition, AM and PM serum 3AG levels in five normal women were similar. We conclude that the high correlation between serum 3AG and urinary 17KS and the absence of a significant circadian variation in 3AG indicate that serum 3AG, regardless of sample time, is a useful metabolic index of integrated adrenal androgen secretion in CVAH.

17-Ketosteroids↗
PubMed1987

Rapid decrease of insulin-specific IgG antibody levels in insulin-dependent patients transferred to semi-synthetic human insulin.

A multicenter, open trial was designed to examine the efficacy and safety of semi-synthetic human insulin (SSHI; Novolin R and Novolin L, SQUIBB-NOVO) in patients with insulin-dependent diabetes mellitus who were transferred from other commercially-available insulins. Whether such a change in therapy would reduce circulating IgG antibodies to antibovine insulin was also evaluated. A total of 68 males and females, 8-62 yr of age, were maintained on their original insulin therapy for 4 weeks, when both glycosylated hemoglobin and fasting blood glucose were assessed. IgG antibody titers to antibovine insulin were also measured. All patients were then transferred to SSHI for a period of 20 weeks. The same variables were evaluated at Weeks 2, 4, 8, and 20. Mean fasting blood glucose levels rose monotonically from 189-226.3 mg/dl over the course of the 20-week clinical trial. There was a slight but insignificant increase in glycosylated hemoglobin by the end of the test period. The average value for antibovine insulin IgG antibodies decreased from 2.54 mu/ml at baseline to 1.32 mu/ml by the completion of the trial. Significant decreases were first observed 4 weeks after the patients were placed on SSHI therapy. After transfer to SSHI, 43.3% of the patients achieved some improvement in glycemic control and only 16.4% were worse than at baseline. A decrease in weekly hypoglycemic reactions occurred during the course of the SSHI therapy. It appears that SSHI provides safe and effective treatment for insulin-dependent diabetic patients and that its use results in a rapid and significant decrease in insulin antibody formation.

Adult↗
PubMed1985

The effect of in vivo glucose administration on human erythrocyte Ca2+-ATPase activity and on enzyme responsiveness in vitro to thyroid hormone and calmodulin.

To characterize endogenous control mechanisms for human erythrocyte membrane Ca2+-ATPase ("calcium pump") activity, we studied the effect of changes in blood glucose concentration in vivo within the physiologic range on Ca2+-ATPase activity in red cells. Red cells obtained in the course of induced hyperglycemia were also studied to determine susceptibility of membrane Ca2+-ATPase to stimulation in vitro by thyroid hormone and calmodulin, both of which have been shown previously to enhance Ca2+-ATPase activity. Oral glucose administration (75 g) to eight healthy, adult subjects induced predictable increases in concentrations of blood glucose and immunoreactive insulin. Basal levels of activity of Ca2+-ATPase in red cells obtained after glucose ingestion fell 55% (P less than 0.025) by 30 min after glucose with recovery of enzyme activity to levels not significantly different from basal by 60 min. Activity of red cell Ca2+-ATPase at time zero was significantly stimulated in vitro by thyroxine (T4, 10(-10) M), triiodo-L-thyronine (T3, 10(-10) M), and calmodulin (100 ng/mg membrane protein). In vivo glucose administration led to depression of red cell enzyme responsiveness in vitro to T4 and T3; recovery from this effect did not occur by 120 min after oral administration of glucose. Calmodulin responsiveness of the enzyme in vitro was less significantly reduced in red cells obtained after glucose ingestion. Intravenous (i.v.) glucose administration (20 g) to five subjects also led to decreased basal enzyme activity (61% of fasting level at 20 min). A significant decrease in response of enzyme to T4 was achieved by 8 min after glucose administration (P less than 0.02), with recovery by 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Male pseudohermaphroditism secondary to an abnormality in Leydig cell differentiation.

We present the first case of a prepubertal male with an abnormality in Leydig cell differentiation resulting in male pseudohermaphroditism. There was no plasma androgen response to im administration of hCG. Leydig cells were not apparently by either light or electron microscopy in tissue obtained from a biopsy of the right testis 96 h after the last dose of hCG. In addition, LH-hCG saturation analyses performed on membrane preparations from the testicular tissue revealed no binding. An expanded classification for male pseudohermaphroditism is presented.

Cell Differentiation↗
PubMed1980

Thyroid function in pediatric patients after neck irradiation for Hodgkin disease.

Thyroid function was evaluated in a consecutively treated group of children and adolescents with Hodgkin disease who received incidental radiation to the thyroid gland. Ten of 27 (36.7%) were found to have elevated concentrations of thyroid-stimulating hormone (TSH). Two groups of patients had an increased incidence of thyroid dysfunction - those who had not had a pretreatment lymphangiogram and those who were less than 13 years of age at the time of neck irradiation. The estimated percentage of patients who did not have a pretreatment lymphangiogram who will develop TSH elevation was 67.7% and of patients who were 13 years of age or less when irradiated, 64.8%. Thyroid dysfunction developed in 6/7 patients who had both of these risk factors present.

Adolescent↗