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Biomedical subjects

G Costin

Publications and source records attributed to G Costin.

At least 19 recordsLinked to original sources
PubMed2001

Autoantibodies and human leucocyte antigen class II in first-degree family members of Mexican-American type 1 diabetic patients.

As part of a genetic study of type 1 diabetes in Mexican-Americans, 360 first-degree relatives of 108 type 1 diabetic probands were studied. Islet cell antibody (ICA), insulin autoantibody, glutamic acid decarboxylase (GAD(65)), and protein tyrosine phosphatase autoantibodies were measured and human leucocyte antigen (HLA) class II alleles DRB1 and DQB1 genotyping was performed. ICA was positive in 37% of the probands and 5.8% of the relatives. A subgroup of 26 probands (12 ICA+, 14 ICA-) was tested for GAD(65) and was found positive. 4/14 ICA+ first-degree relatives were GAD(65) positive. Four relatives, positive for two antibodies, subsequently developed type 1 diabetes. Life-Table analysis of first-degree relatives with autoantibodies indicated an 80% disease-free survival at 3.5 yr. HLA-DRB1 was found to be associated with the presence of ICA in both probands and relatives, whereas HLA-DPB1 was associated with autoantibody in relatives of type 1 diabetic probands. These results suggest that autoimmunity occurs in type 1 diabetes families of Mexican descent in similar frequencies to that of non-Hispanic, Caucasian families. The presence of autoantibodies appears to be regulated in part by HLA class II genes, even in the absence of overt diabetes.

Adolescent↗
PubMed1997

Differential effect of gender on the sizes of the bones in the axial and appendicular skeletons.

Recent observations suggest that throughout life the size of the vertebral bodies in females is smaller than that in males even after accounting for differences in body size. To confirm these reports and to determine whether similar differences exist in the appendicular skeleton, detailed measurements of the sizes of the vertebrae and the femur were obtained using computed tomography in 30 pairs of prepubertal boys and girls matched for age, height, and weight. Anthropometric parameters as well as gender influenced the cross-sectional area of the vertebrae. Heavier children had greater vertebral cross-sectional area than slender children regardless of gender, and the vertebral bodies were found to be significantly smaller in girls than in matched boys (approximately 11%), both using Student's t test (P < 0.0001) and its multivariate analog, the Hotelling's T2 test (P < 0.0001). In contrast to these findings in the axial skeleton, gender status did not influence the size of the bones in the appendicular skeleton, and neither the cross-sectional area (3.28 +/- 0.84 vs. 3.10 +/- 0.56 cm2) nor the cortical bone area (1.80 +/- 0.37 vs. 1.85 +/- 0.36 cm2) at the midshaft of the femur differed between boys and girls. These values, however, correlated strongly with all anthropometric indexes, and multiple regression analyses indicated that both measurements were primarily related to weight. The results suggest that although increases in mechanical loading associated with growth are the main determinant of the cross-sectional properties of the appendicular skeleton in children, factors other than body mass and related to gender have a significant role in the regulation of the sizes of the bones in the axial skeleton.

Body Weight↗
PubMed1995

Continuous subcutaneous insulin infusion (CSII) in children and adolescents with chronic poorly controlled type 1 diabetes mellitus.

This study was undertaken to determine if continuous subcutaneous insulin infusion (CSII) could improve control, diminish episodes of diabetic ketoacidosis (DKA), decrease number of hospitalizations and save health care expenditure in children and adolescents with long-standing poorly controlled diabetes mellitus. A retrospective analysis was done of six patients with type 1 diabetes for 1-8 years, of whom 4 were non-adherent to the diabetic regimen (ages 12-16.5 years) and 2 of whom had brittle diabetes (ages 8.5 and 10 years). These patients were non-randomly placed on the MiniMed (Sylmar, CA) CSII system. The year prior to CSII was compared with the year during pump use. Glycoslyated hemoglobin (HbA1c), spot urinary microalbumin, total cholesterol, insulin dose, growth velocity, number of convulsions and hypoglycemic events, number of episodes of DKA, number of hospitalizations and total inpatient costs were compared for the 2 years. The year prior to CSII, mean HbA1c was 9.02% (S.D. = 0.86%), mean number of hospitalizations was 5.2/patient (S.D. = 4.6), mean number of hospital days was 20.8/patient (S.D. = 14.7) and mean cost was $29330/patient (S.D. = $22804). During 1 year of CSII, mean number of hospital days decreased to 5 days/patient (S.D. = 0.8, P = 0.016), mean number of hospitalizations (including DKA and pump initiation) decreased to 1.7/patient (S.D. = 0.7, P = 0.31), mean inpatient costs decreased to $12762/patient (S.D. = $5.950, P = 0.047). HbA1c, urinary microalbumin, cholesterol, insulin dose and growth velocity did not change in a statistically significant manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Growth hormone effects on wound healing in malnourished animals: a histological study.

Systemic growth hormone (GH) markedly improves celiotomy wound strength in protein malnourished (PM) animals. This study was undertaken to analyze the effect of GH as a basis for anatomically understanding. Adult female Spraque-Dawley rats were divided into normally nourished controls, PM and GH-treated PM groups. Protein malnutrition was achieved by feeding 5.5% protein restricted chow every other day for eight weeks before surgery. Controls were fed 23.4% protein chow. All animals were fed 23.4% protein chow postoperatively. Rat-GH was injected subcutaneously twice daily (1.0 mg/day) for three days prior to and five days after 5 cm midline celiotomy. Bursting strength of the wound was measured at 3, 6 and 14 days postoperatively. Histologic wound specimens (hematoxylin and eosin) were obtained from each group. Wound strength of malnourished rats was significantly less than that of normal controls at six days after operation (p < 0.001). With administration of growth hormone, the wound strength was significantly improved. Histologically, there was no difference between groups on day 3. On day 6 the normal control group showed a decrease in the early inflammatory cell infiltrate with concurrent development of granulation tissue and a dense proliferation of fibroblasts. The PM wound showed fatty infiltration, a very narrow band of poorly formed granulation tissue and a sparse fibroblastic proliferation. The GH-treated PM group showed a combination of histologic findings. Fatty infiltration, similar to that in malnourished non-treated animals, was still evident but there was also a dense proliferation of capillary channels and fibroblasts comparable to normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families.

The role of HLA class II alleles in genetic predisposition to insulin dependent diabetes mellitus (IDDM) was examined by PCR/oligonucleotide probe typing of 42 Mexican-American IDDM families derived from Hispanic Caucasians and Native Americans. All high risk haplotypes (HLA-DR3 and DR4) were of European origin while the most strongly protective haplotype (DRB1*1402) was Native American. Of the 16 DR-DQ DR4 haplotypes identified, only those bearing DQB1*0302 conferred risk; the DRB1 allele, however, also markedly influenced IDDM risk. The general pattern of neutral and protective haplotypes indicates that the presence of Asp-57 in the HLA-DQ beta chain does not confer IDDM protection per se and indicates that both DRB1 and DQB1 influence IDDM susceptibility as well as protection.

Alleles↗
PubMed1993

Analysis of HLA-DQA1 and -DQB1 genes in Mexican Americans with insulin-dependent diabetes mellitus.

Mexican American patients (n = 35) with insulin-dependent diabetes mellitus (IDDM) and control subjects (n = 39) were HLA-DQA and DQB typed by the polymerase chain reaction technique combined with allele-specific oligonucleotide probes. Either DQB1*0302 or DQB1*0201 was present among 91% (32/35) of the patients compared to 67% (26/39) of controls. Either DQA1*0501 or DQA1*0301 was present in all patients (100% or 35/35) compared to 29/39 (74%) (OR 12.06 Pc < 0.05) of controls. All four of these genes, in cis or trans, were present in 15/35 (43%) of the patients compared to 3/39 (8%) of controls (OR 9.0; Pc < 0.01). The presence of one or more non-susceptibility alleles showed a dose-related decrease in relative risk. Presence of aspartic acid (Asp) at position 57 of the DQ beta chain did not confer protection and non-Asp homozygosity did not confer susceptibility to IDDM in this ethnic group. In conclusion, susceptibility to IDDM in Mexican Americans is associated with particular DQA and DQB combinations, illustrates dose-dependent parameters and contradicts the critical residue hypothesis.

Adult↗
PubMed1992

Benign testicular tumors in children with congenital adrenal hyperplasia.

The association between testicular tumors/nodules and congenital adrenal hyperplasia (CAH) has been previously reported. From 1960 to 1989, three patients (13 to 18 years old) with long-standing CAH developed testicular masses. Two patients with 21-hydroxylase deficiency were diagnosed in the neonatal period while one other with 11-hydroxylase deficiency was diagnosed at 3 years of age when he presented with sexual precocity. In all three patients, medical compliance was poor. The testicular masses were bilateral in two patients and unilateral in one, measured 1 to 2 cm, and occupied only the upper half of the testicle. Testicular biopsy specimens were obtained after at least 6 months of evidence of compliance with the adrenocorticotrophic hormone (ACTH) suppressive medication and failure of the nodules to regress. On gross examination the masses appeared to be firm yellow brown nodules. Light microscopy showed interlacing strands, cords, and rests of cells resembling interstitial (Leydig) cells but with no Reinke crystalloids. Electronmicroscopy in all patients showed variable amounts of both smooth and rough endoplasmic reticulum, the later with occasional dilated cisternae. Follow-up ranged from 6 months to 6 years. No further surgical treatment has been necessary. There has been no evidence of recurrence, distant metastases, or secondary malignancies during the time of follow-up. These findings suggest that testicular tumors may develop from chronic excessive ACTH stimulation of a putative pluripotential testicular cell, a Leydig cell, or an adrenal cortical rest. Unlike other testicular tumors these do not require orchiectomy as the initial form of therapy.

Adolescent↗
PubMed1992

Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids.

Corticosteroid (CS) administration amplifies the inhibitory effect of protein malnutrition (PM) on wound healing. Abdominal surgery in protein malnourished patients receiving corticosteroids (eg, advanced malignancy, transplant recipients) may be complicated by wound dehiscence or anastomotic breakdown. Although preoperative parenteral nutrition can reduce the incidence of these complications, this is not possible in patients requiring urgent surgical intervention. In a previous report we demonstrated that postoperative growth hormone (GH) administration could restore normal wound healing in PM rats. This study evaluates the effect of GH on wound healing in PM rats treated with CS. Forty-eight female Sprague-Dawley rats weighing 180 to 210 g were divided into four groups: (1) normally nourished; (2) PM only; (3) PM + CS; and (4) PM + CS + GH. PM rats (groups 2 to 4) received 5.5% protein chow every other day for 8 weeks. Control rats (group 1) received 23.4% protein chow for the same duration. Group 3 and 4 rats received prednisolone (2 mg/kg, intramuscularly) during the last 3 weeks of PM. All animals underwent precise 5-cm midline celiotomies. Postoperatively, rats in all groups were given 23.4% protein chow. Group 3 and 4 rats continued to receive CS postoperatively. Group 4 rats were given GH (0.5 mg/d, intraperitoneally) postoperatively for 5 days. Wound testing was performed on the 6th postoperative day after removal of the sutures. A balloon inserted into the peritoneal cavity through the vagina was gradually inflated. The pressure at which the wound disrupted was recorded as the wound bursting strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1992

Testicular feminization: the androgen insensitivity syndrome.

Testicular feminization (TF) is a syndrome due to androgen insensitivity. It occurs in a complete (CTF) and an incomplete (ITF) form. We have treated 21 patients with TF over the last 24 years. Eight patients presented because of ambiguous genitalia, seven presented as "females" with inguinal hernia and testes were found at surgery, five were diagnosed by karyotyping performed for a family history of TF, and one presented with an incarcerated hernia and primary amenorrhea. Two patients had prior surgery for inguinal hernia but the diagnosis was not recognized. All patients had a 46,XY karyotype. Patients with CTF were phenotypically female while those with ITF had a variable appearance of the external genitalia depending on the degree of androgen insensitivity. Seventeen patients underwent gonadectomy and one patient planned for delayed gonadectomy was lost to follow-up. Seventeen patients had been raised as females since birth. One patient with ambiguous genitalia, who was initially raised as a male, was reassigned female gender at 1 year of age when the diagnosis of ITF was made. Three patients were raised as males even after the diagnosis of ITF was made. Patients raised as males underwent multiple genital reconstructive procedures with poor results. In view of the poor anatomic and functional results of genital reconstructive surgery and the consequent psychological problems, patients with TF should be raised as female. Careful evaluation of infants with ambiguous genitalia and documentation of absent fallopian tubes in "females" presenting with inguinal hernia will lead to early diagnosis of TF, correct sex assignment, and early gonadectomy.

Adolescent↗
PubMed1992

Ancestral origin of insulin-dependent diabetes in Mexican-Americans.

To test the hypothesis that insulin-dependent diabetes mellitus in the Mexican-American population is due to Spanish genetic admixture, we obtained ancestral information on 106 Mexican-American families with an insulin-dependent diabetic index case and 80 Mexican-American control families from 1987 to 1991. The Mexican states of origin were available on 395 grandparents of the insulin-dependent diabetic index cases and 291 grandparents of the controls. Analysis of the individual states of origin revealed that there were significantly more Mexican-American grandparents of diabetic index cases from the states of Jalisco and Michoacan when compared to the control families (31% and 16% diabetic versus 22% and 11% controls respectively, P less than 0.01). The states of Zacatecas and Durango had a lower frequency of diabetic grandparents as compared to controls (6% diabetic versus 12% controls, P less than 0.001). Analysis of the origin by Northern and Southern states of México revealed a significant decrease in the number of grandparents of the insulin-dependent diabetic cases from the Northern regions of México, 19.5%, versus 32% in controls, (P less than 0.001). These data indicate that the grandparents of the insulin-dependent diabetic index cases originate from states and regions of México which were those of the early entry of the Europeans. These data thus support the hypothesis that insulin-dependent diabetes mellitus in the Mexican-American population may be due in significant part to an original genetic contribution from the Spanish-European population.

Adolescent↗
PubMed1992

Subcutaneous growth hormone-releasing hormone therapy in growth hormone-deficient children: first year of therapy.

The purpose of this study was to determine the efficacy and safety of GH-releasing Hormone [GHRH-(1-44)] therapy in GH-deficient children. Twenty previously untreated prepubertal children with GHRH deficiency were treated for 1 yr in a multicenter, open label, company-sponsored study with at least 20 micrograms/kg GHRH-(1-44), sc, half at bedtime and half upon awakening. The main effects were enhancement of linear growth, advancement in bone age, and alteration in general blood chemistries and hormonal values. The mean velocity of the entire group increased from 3.6 +/- 1.1 to 8.1 +/- 1.5 cm/yr (P < 10(-4)) at 1 yr of therapy. After 6 months of therapy, 16 were growing at a mean of 9.4 +/- 2.0 cm/yr and were continued on this dose. In 4 patients who were growing at a rate of 5.5 +/- 1.7 cm/yr, the dose was increased to 40 micrograms/kg daily for the second 6 months. The high dose group increased their mean linear growth velocity for the second 6 months while on the higher dose to 7.6 +/- 0.4 cm/yr (P < 10(-2)). This was equal to the mean velocity for the second 6 months of therapy of the 16 subjects who remained on the 20 micrograms/kg daily therapy (7.6 +/- 1.2 cm/yr). Mean advancement of bone age was 1.3 +/- 0.6 yr during the first year of therapy. No adverse changes in general biochemical, hormonal, or pituitary radiographic analyses were noted. No change in fasting glucose or insulin concentrations, or excessive generation of insulin-like growth factor-I concentrations occurred. We conclude that GHRH in a daily dose of 20-40 micrograms/kg for 1 yr was effective in increasing growth velocity in most GHRH-responsive GH-deficient patients. It was well tolerated without side-effects. Glucose intolerance was not noted.

Adolescent↗
PubMed1991

Changes in vertebral bone density in black girls and white girls during childhood and puberty.

BACKGROUND: The prevalence of osteoporosis and the incidence of vertebral fractures are lower in black women than in white women, findings generally attributed to racial differences in adult bone mass. Little is known, however, about the factors that contribute to racial variations in bone mass or the time of life when such differences become manifest. This study was done to characterize the changes in vertebral bone density at various stages of sexual development in black and white females. METHODS: We measured cancellous vertebral bone density by quantitative computed tomography in 75 black female subjects between 2 and 20 years old and 75 whites matched for age and stage of sexual development. RESULTS: The vertebral bone density did not differ between black girls and white girls before puberty. Bone density increased during puberty in each racial group, but the magnitude of the increase from prepubertal values was substantially greater in black than in white subjects (34 percent vs. 11 percent). CONCLUSIONS: The marked difference between black and white females in cancellous vertebral bone density occurs during a relatively brief period late in puberty. Metabolic and hormonal events related to the achievement of sexual maturity during adolescence may be important determinants of racial differences in bone mass in women.

Adolescent↗
PubMed1991

Vertebral bone density in insulin-dependent diabetic children.

To determine the effect of insulin-dependent diabetes mellitus (IDDM) on bone mass, we compared the trabecular and cortical bone density in lumbar vertebrae, measured by quantitative computed tomography (CT), in 48 white diabetic patients (23 females, 25 males; 5.2 to 19.6 years of age) with those of a control group of 48 healthy subjects, matched for race, sex, and age. Patients with neuropathy, retinopathy, nephropathy, and those with recent ketoacidosis were excluded from the study. The patient and control groups did not differ in sexual or skeletal maturation, weight, height, surface area, body mass index, abdominal fat, or paraspinal musculature. In diabetic children, cortical bone density was slightly but significantly lower than in controls (3.5% lower, P less than .02); there was no difference between patients and controls regarding trabecular bone density. The decrease in cortical bone density in the diabetic group did not correlate with age, sex, duration of diabetes, or glycosylated hemoglobin levels. These results suggest that in children with uncomplicated IDDM, decreased vertebral bone density is a minor abnormality that only affects cortical bone.

Adolescent↗
PubMed1991

Blood glucose control and albuminuria in type 1 diabetes mellitus.

The relationship between long-term blood glucose control and albuminuria in type 1 diabetes was investigated in 42 male and 58 female patients who had had diabetes mellitus for more than 7 years. Their mean (+/- SD) age and diabetes duration were 18.6 +/- 3.6 and 12.1 +/- 3.5 years, respectively. For periods of observation ranging from 1 to 6 years (mean 4.4 +/- 1.5), hemoglobin A1c (HbA1c) was measured two to six times yearly (mean of 8.8 +/- 3.9 determinations per patient). Albumin excretion rate (AER) was measured in single-void urine samples two to four times in 93 patients and once in the other seven patients. The 52 patients with mean HbA1c no more than 9.0% had significantly lower mean AER than those whose HbA1c was greater than 9.0% (20.1 +/- 24.6 vs 265 +/- 1005 mg/gm Cr, p less than 0.001). Only five (9.6%) of these 52 patients had elevated AER values (greater than 40 mg/gm Cr), whereas 21 (43.7%) of 48 patients whose mean HbA1c was greater than 9.0% had elevated AER values (p less than 0.001). Six male but no female patients had mean AER values greater than 300 mg/gm Cr. The 74 patients with normal AER had significantly lower mean HbA1c values than the 26 with elevated AER (8.6 +/- 1.5 vs 10.1 +/- 1.6%, p less than 0.001). These results support the contention that maintenance of HbA1c levels at no more than 9% (one and one-half times the upper limit of normal) will significantly decrease the likelihood that diabetic nephropathy will develop.

Adolescent↗
PubMed1990

Stimulation of wound bursting strength during protein malnutrition.

Nutrition is one of the most important factors affecting wound healing. Patients who have significant protein malnutrition and require emergency surgery are frequently encountered. Conventional nutritional preparation for surgery, with intravenous hyperalimentation, requires 10 to 14 days to demonstrate advantageous reversal of catabolism. Growth hormone is known to have an anabolic effect in malnourished animals. The purpose of this investigation was to study the ability of growth hormone, administered from the time of celiotomy, to improve wound strength in protein-malnourished animals and compare its efficacy with preoperative nutritional repletion. Rats were divided into four groups: Group I--normal control rats, group II--malnourished rats, group III--malnourished rats treated with growth hormone for 5 postoperative days, and group IV--malnourished rats refed normal chow for 3 days before operation. Controlled laparotomy wounds were closed with monofilament nylon which was removed at the time wound bursting strength was tested. Bursting strengths at the sixth day postoperative were as follows (means +/- SD): (table; see text) Wound strength of malnourished animals was significantly less than that of controls, (P less than 0.001). Wound bursting strength of groups III and IV was significantly improved over that of malnourished animals (group II), P less than 0.001. The bursting strength of group IV was significantly higher than that of group III. Growth hormone administration following celiotomy is nearly as effective in improving wound healing as preoperative nutritional repletion. These results suggest that growth hormone may be clinically applicable in preventing wound complications in malnourished patients requiring urgent or emergency laparotomy.

Abdomen↗
PubMed1990

The effect of perioperative exogenous growth hormone on wound bursting strength in normal and malnourished rats.

Patients with significant malnutrition secondary to underlying disease may require major surgical intervention on an urgent basis. Nutritional restoration using enteral or intravenous alimentation requires a delay of 10 to 14 days and is frequently not practical. With the availability of human growth hormone (GH) produced by recombinant DNA technology, this study was undertaken to evaluate the effect of exogenous GH on wound tensile strength in a rat model. Fifty-four animals were divided into three groups: group I, normal nourished control; group II, malnourished; group III, malnourished, rat GH treated (1 mg GH administered 3 days preoperative and 5 days postoperative celiotomy). Wound tensile strength was measured at 6 days postoperatively. Wound strengths in malnourished rats were significantly less than in normal controls (P less than .001). With the administration of growth hormone in group III, wound strength was significantly improved when slightly improved over normally nourished controls (P less than .05). A dose response curve demonstrated progressive improvement in wound tensile strength from 0.01 mg/d to 1.0 mg/d. Thus growth hormone administration to malnourished animals significantly enhances wound strength. With the availability of recombinant produced human GH these observations may be clinically applicable.

Abdominal Injuries↗
PubMed1989

Growth hormone secretory dynamics in subjects with normal stature.

To evaluate the dynamics of growth hormone (GH) secretion in subjects with normal stature and to determine whether a correlation exists between height and the quantity of GH secreted, we determined the 24-hour GH concentration by measuring GH levels every 30 minutes in 27 boys and 19 girls of normal height, 7 to 18 years of age, of whom 24 were prepubertal and 22 in various stages of puberty. Spontaneous GH secretion had wide variations, with values ranging from less than 1.0 to 67.0 micrograms/L. In prepubertal children the highest GH levels were usually noted during sleep; in pubertal subjects the highest values were distributed almost equally between sleep and wake hours. In all subjects, GH secretion appeared to decrease before meals, followed by an increase after meals. Most indexes of GH secretion and insulin-like growth factor I levels were significantly greater in pubertal than in prepubertal subjects (p less than 0.002), and in both groups the GH concentration was significantly greater during sleep (p less than 0.005). In all groups the 24-hour GH concentration correlated significantly with the area under the GH curve, 24-hour GH pulse amplitude, and GH concentration and peak GH level during sleep and wake hours (P less than 0.0001); 24-hour GH concentrations correlated with insulin-like growth factor I levels only when the entire group of 46 subjects was considered (p less than 0.01). There were no significant correlations between 24-hour GH concentration and the subjects' age, bone age, height (SD score), weight (SD score), or body mass index. We conclude that in subjects with normal stature, mean 24-hour GH concentrations vary considerably and in the low range overlap with values reported in hypopituitarism.

Adolescent↗