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Biomedical subjects

F R Kaufman

Publications and source records attributed to F R Kaufman.

At least 55 records · Page 3Linked to original sources
PubMed1989

Deficit of uridine diphosphate galactose in galactosaemia.

The levels of uridine diphosphate galactose (UDPGal) and uridine diphosphate glucose (UDPGlc) have been determined in liver autopsy samples, erythrocytes and cultured skin fibroblasts from galactosaemic patients and compared to non-galactosaemic controls. In patients with undetectable erythrocyte galactose-1-phosphate uridyltransferase (transferase) activity, the levels of UDPGal were substantially lower than in controls. In patients with detectable transferase activity, even though in less than 1% of normal values, both UDPGal and UDPGlc levels were in the normal range. Incubation of erythrocytes from both galactosaemic patients and normal individuals with 10 mmol/L uridine increased UDPGal and UDPGlc levels several-fold, both in the presence or absence of galactose in the incubation medium. We hypothesize that a deficit of UDPGal is responsible for the late onset clinical manifestations in galactosaemia which include ovarian failure, speech defect and neurological abnormalities. We suggest that uridine administration may be of therapeutic value in raising the intracellular concentrations of UDPGal. We conclude that the transferase reaction, however small in activity, is essential for optimal UDPGal formation.

Cells, Cultured↗
PubMed1989

Uridine nucleotide sugars in erythrocytes of patients with galactokinase deficiency.

The levels of UDPglucose and UDPgalactose (UDPGal) have been measured in erythrocytes of seven patients with galactokinase deficiency. Normal levels of UDPGal were found in all patients with galactokinase deficiency (McKusick 23020). This is in contrast with reduced values of UDPGal found in patients with classical galactosaemia who have complete absence of galactose-1-phosphate uridyl transferase activity. It was demonstrated that patients with galactokinase deficiency had an incomplete enzyme block in erythrocytes by direct enzyme assay, by 14CO2 production from [1-14C]galactose, and by the appearance of labelled intermediates, notably galactose-1-phosphate and UDPhexose.

Adolescent↗
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↗
PubMed1989

Galactose metabolism in human ovarian tissue.

Galactose metabolism was studied in human ovarian tissue obtained from 14 women controls between 21 and 72 y of age, and one 21-y-old galactosemic patient with hypergonadotrophic hypogonadism. Tissue slices were incubated with 1-14C-galactose, and labeled intermediates were analyzed by anion-exchange column chromatography. Activities of enzymes related to the galactose pathway: galactokinase, transferase, epimerase, uridine diphosphoglucose (UDPGlc) and uridine diphosphogalactose pyrophosphorylases, and UDPGlc and uridine diphosphogalactose pyrophosphatases were measured in ovarian homogenates using radioisotopic, spectrophotometric, and fluorometric techniques. Incorporation of carbon label from 1-14C-galactose into various galactose and glycolytic intermediates, as well as carbon dioxide and TCA-insoluble materials was demonstrated in samples from non-galactosemic controls. In tissue from the galactosemic individual, no labeled carbon dioxide was produced and very little incorporation into TCA-insoluble material was found. Labeled galactose-1-phosphate was elevated. In normal ovarian tissue, specific activities of galactokinase, transferase, epimerase, and UDPGlc pyrophosphorylase are much higher than those found in the red cells and in testes. UDPGlc pyrophosphorylase activity is about 50 times that of transferase, suggesting that uridine nucleotide sugars have an important role in the normal development and function of the ovary. It is hypothesized that premature ovarian failure, often observed in patients with galactosemia, is due to interference with nucleotide sugar metabolism and the synthesis of galactose containing glycoproteins and glycolipids consequent to the enzymatic defect in the major pathway of galactose metabolism.

Adult↗
PubMed1989

Gonadal function and ovarian galactose metabolism in classic galactosemia.

Evaluation of ovarian steroid secretion, histologic examination of ovarian tissue, and incubation studies with radiolabelled galactose in ovarian tissue slices were performed in a 21-year-old woman with galactosemia and incipient ovarian failure. After exogenous gonadotropin administration in an attempt to achieve fertility, there was no evidence of ovulation by ultrasound; estrogen and androgen production were deficient indicating ovarian unresponsiveness. Histologic examination of the ovary revealed that the ovarian stroma had an increase in fibrous tissue and that a few hyalinized atretic follicles were present with no intermediate or evolving Graafian follicles. After incubation with galactose-1-14C, there was absence of labelled CO2 production and only labelled galactose-1-phosphate was identified as compared to controls in which several labelled intermediates could be seen. The incorporation of galactose into the TCA-insoluble fraction was drastically reduced in the patient compared to controls, suggesting that there may be a deficiency of ovarian galactose-containing glycolipids, glycoproteins and mucopolysaccharides in the galactosemic ovary. Deficiency in the production of galactose containing compounds, or galactose-1-phosphate accumulation or both, may lead to the development of hypergonadotropic hypogonadism seen in women with galactosemia.

Adolescent↗
PubMed1989

Growth failure in boys with hemophilia and HIV infection.

The growth of 22 boys with hemophilia, infection with human immunodeficiency virus (HIV), and lymphadenopathy, but not overt acquired immunodeficiency syndrome (AIDS) was evaluated. Three patients were found to have significant growth failure for 3-4 years with the onset after HIV infection. Extensive endocrine evaluation revealed that two of the three had neurodysregulation of growth hormone release with hyposomatomedinemia. None had classical growth hormone deficiency, thyroid deficiency, or evidence of malnutrition/malabsorption or other systemic illness. It appears that growth failure is not rare in boys with hemophilia and HIV infection and that this might be due to a direct effect on the physiologic secretion of growth hormone.

AIDS-Related Complex↗
PubMed1987

Growth hormone secretory patterns in children with short stature.

To assess whether growth-retarded children with a stimulated growth hormone (GH) level greater than 10 ng/mL have an abnormality in spontaneous GH secretion, we measured GH levels every half hour for 24 hours in 50 children 2.7 to 17 years of age. Growth rate was subnormal in all. Mean 24-hour GH concentration ranged from 1.2 to 7.7 ng/mL, and was significantly greater in pubertal than in prepubertal children (P less than 0.01). In both groups, GH concentration during sleep was significantly greater than during wakeful hours (P less than 0.0005); 24-hour GH concentration correlated significantly with sleep-induced GH peak. A decrease in 24-hour GH concentration and sleep-induced GH peak were noted in four pubertal children with stimulated GH less than 15 ng/mL. A progressive and significant increase in somatomedin C (SmC) level was noted with increasing age and sexual development. No correlations were found between 24-hour GH concentration and rate of growth, age, or bone age. Serum SmC values correlated significantly with age and bone age (P less than 0.01), and with 24-hour GH concentration only in prepubertal children (P less than 0.05). A strong correlation between SmC and growth rate was noted only in pubertal children (P less than 0.01). Growth velocity increased significantly during GH therapy regardless of the 24-hour GH concentration. Our results indicate that in children with growth retardation there is a wide variation in 24-hour GH concentration and a significant increase in GH concentration during puberty; the GH concentration during nocturnal sleep, rather than an entire 24-hour GH concentration, can be used for evaluation; during puberty the SmC level reflects sexual development more than GH reserve; and GH therapy appears to increase growth velocity in both non-GH-deficient and partially GH-deficient short children.

Adolescent↗
PubMed1986

Gonadal function in patients with galactosaemia.

Gonadal function was followed in 26 females and 12 males with galactosaemia due to deficiency of the enzyme galactose-1-phosphate (Gal-1-P) uridyl transferase over a 4 year period. Gonadal function was normal in males, but all females except two had evidence of acquired ovarian failure. Twelve females with ovarian failure documented at the beginning of this study continued to have either primary or secondary amenorrhoea on follow-up. Five of six patients, who previously had normal gonadal function developed either hypergonadotrophic hypogonadism or an abnormal response to gonadotrophin-releasing hormone (LRH) indicative of acquired ovarian damage. Seven of eight female patients, 1-12 years of age, who were evaluated for the first time had an exaggerated release of gonadotrophins during LRH stimulation tests diagnostic of gonadal insufficiency. The pathogenesis of ovarian failure remains unknown, but it appears likely that galactose or Gal-1-P is toxic to the ovary. The source of galactose metabolites, which may begin to accumulate prenatally and continue to damage the gonad in the postnatal period, is likely to be derived from the diet and from the endogenous synthesis of Gal-1-P from glucose via a variety of metabolic pathways. The testis appears to be relatively resistant to the effects of abnormal galactose metabolism.

Adolescent↗
PubMed1986

Autonomous ovarian hyperfunction followed by gonadotrophin-dependent puberty in McCune-Albright syndrome.

A 5-year-old girl with the McCune-Albright syndrome presented with precocious puberty secondary to autonomously functioning ovarian cysts, followed by true central puberty. Progression from gonadotrophin-independent to gonadotrophin-dependent precocious puberty may occur from elevated sex steroid levels leading to the early maturation of the hypothalamic-pituitary axis.

Child, Preschool↗
PubMed1984

Neonatal cholestasis and hypopituitarism.

The diagnosis of optic nerve hypoplasia and hypopituitarism must be entertained in infants who present for evaluation of cholestatic jaundice, particularly if there is associated hypoglycaemia and wandering nystagmus. Although the hepatic dysfunction seems to resolve, the long term prognosis of liver disease in optic nerve hypoplasia remains unknown.

Cholestasis↗
PubMed1983

Male pseudohermaphroditism due to 17,20-desmolase deficiency.

In a 5-yr-old 46,XY male pseudohermaphrodite with microphallus, perineal hypospadias, chordee and cryptorchidism, serum C19 steroid levels were abnormally low in the basal state and after adrenal and testicular stimulation. Serum C21 steroid levels were elevated in the basal state and increased further after adrenal, but not after gonadal, stimulation. Urinary excretion of pregnanetriolone, a metabolite of 17-hydroxypregnenolone and 17-hydroxyprogesterone not normally present in the urine, was increased in the basal and stimulated states. Cortisol production was normal, and all steroid hormone levels were suppressed by dexamethasone. Testicular biopsy was consistent with prepubertal cryptorchid testes. Incubation of testicular tissue with labeled 17-hydroxyprogesterone revealed failure of conversion of precursor to androstenedione and testosterone. A significant increase in phallic length occurred after treatment with exogenous androgen. These findings are consistent with 17,20-desmolase deficiency in both gonads and adrenal glands.

Adolescent↗
PubMed1982

Metastatic medullary thyroid carcinoma in young children with mucosal neuroma syndrome.

Multiple endocrine neoplasia, type 2b (MEN 2b) is a disorder characterized by a distinct phenotype and a predisposition for medullary thyroid carcinoma (MTC) and pheochromocytoma. Two siblings aged 3 and 6 years with MEN 2b, who had elevated plasma calcitonin levels suggesting the presence of MTC are described. Microscopic foci of MTC were found in their thyroid glands and the glands were removed. In the younger child, a metastatic focus was present in a cervical lymph node. Of 12 previously reported children with MEN 2b and MTC who were less than 10 years of age at diagnosis, five had metastases. One of the present patients is the youngest described with this complication. The high frequency of metastases in very young patients with this syndrome has not been emphasized previously. These findings indicate the need for early diagnosis of MEN 2b and the importance of thyroidectomy at the earliest possible age when MTC is suspected by calcitonin screening tests.

Adult↗
PubMed1981

Hypergonadotropic hypogonadism in female patients with galactosemia.

We evaluated gonadal function in 18 female and eight male patients with galactosemia due to transferase deficiency; it was normal in the males, but 12 females had signs of hypergonadotropic hypogonadism. All female patients had a 46,XX karyotype, normal levels of thyroid hormone and prolactin, and no anti-ovarian antibodies. The biologic activity of urinary gonadotropins was normal. Ultrasonography of the pelvis revealed that ovarian tissue was diminished or absent. Total estrogens increased in one of two patients after administration of human menopausal gonadotropin. The frequency of hypergonadotropic hypogonadism was higher in females in whom dietary treatment for galactosemia was delayed. Clinical course and mean erythrocyte galactose-1-phosphate and urinary galactitol levels did not correlate with ovarian function. We conclude that female patients with galactosemia have a high incidence of ovarian failure due to acquired ovarian atrophy. Galactose or its metabolites may be toxic to the ovarian parenchyma, particularly during the immediate neonatal period.

Adolescent↗
PubMed1979

Orbital rhabdomyosarcoma in a neonate.

A newborn with a pleomorphic rhabdomyosarcoma of the eyelid was treated by chemotherapy, surgery, and radiation therapy and experienced a good response. The nine previous cases in the literature are reviewed and this patient's therapy discussed.

Antineoplastic Agents↗
PubMedDate not supplied

Insulin pump therapy in type 1 pediatric patients: now and into the year 2000.

There are a number of medical conditions such as growth failure in children, pregnancy, lipid abnormalities, and early complications that are improved by the meticulous glycemic control that can be achieved with insulin pump therapy (CSII). By using an insulin pump, many patients with severe hypoglycemia, the dawn phenomenon, extremes of glycemic excursion, recurrent diabetic ketoacidosis (DKA) and hypoglycemia unawareness have amelioration of these problems. However, pump therapy involves problems such as weight gain, recurrent ketosis due to pump failure, infections, and risk of hypoglycemia. Owing to many developmental issues, young children may not be able to wear the pump without parental supervision. We have used the pump at night time only in these patients. This has allowed children of 7-10 years of age to benefit from improved nocturnal glycemia without the risk of pump therapy when they are without an adult to help. We have also used the pump in subjects with recurrent DKA and in our general patient population (mean age 13.6+/-3.9 years). In our pump cohort, CSII led to improvement in quality of life, knowledge, adherence, and responsibility. A reduction in hypoglycemia, DKA rate and mean HbA(1c) was associated with pump usage. For this to occur, however, pump education must be geared to the pediatric subject and his/her family. Education materials and tools help in learning how to use the pump and how to deal with the intricacies of basal and bolus dosing, and the effect of exercise, food and illness on diabetes management. The pump has improved since it was first introduced and these modifications have made it easier, more painless and less hazardous. With the development of continuous glucose sensors and implantable pumps, the next century will see pump therapy lead to the artificial pancreas.

Adolescent↗