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Biomedical subjects

S F Kemp

Publications and source records attributed to S F Kemp.

At least 37 records · Page 2Linked to original sources
PubMed1991

Hypertrophy of clitoral hood: presenting sign of neurofibromatosis in female child.

Although clitoral involvement with neurofibromatosis is rare, all cases previously reported have described clitoral hypertrophy due to neurofibromas of the clitoral corpora. We report on a patient who had localized enlargement of the prepuce only, with no evidence of neurofibromatous infiltration. In all cases, diagnosis of clitoromegaly requires basic chromosomal and endocrinologic evaluation. However, recognition of its association with neurofibromatosis due to either neurofibromas of the genitalia or localized genital hypertrophy may spare the patient an unnecessary or invasive evaluation. Because of an association with urinary tract neurofibromas, the patient with genital involvement should have cystoscopy. Clitoroplasty with sparing of the neurovascular bundle and glans is the preferred method of management of the enlarged clitoris.

Child, Preschool↗
PubMed1991

Effect of metabolic control on serum protein concentrations in diabetes.

Serum albumin, transferrin, transthyretin (prealbumin), and retinol binding protein concentrations were determined in 74 children with insulin-dependent diabetes mellitus before and after a 10-day camp session during which blood glucose concentrations were controlled. Initial concentrations of albumin and transferrin in the subjects were not different from those in 21 children and adults without diabetes, and did not change during the study period. Transthyretin and retinol binding protein concentrations were lower in subjects with diabetes than in the control population, and increased from 182 +/- 49 mg/l and 42.5 +/- 13.4 mg/l to 232 +/- 71 mg/l and 47.2 +/- 13.5 mg/l, respectively. We observed correlations between the changes in transferrin, transthyretin, and retinol binding protein. Although reductions in glycated albumin and transferrin indicated improvement in blood glucose control, there was no correlation between changes in the glycated markers and the concentrations of serum transport proteins. Thus, serum protein concentrations were influenced by the metabolic control of diabetes, but did not directly reflect blood glucose.

Adolescent↗
PubMed1991

Single and multiple dose pharmacokinetics of methionyl growth hormone in children with idiopathic growth hormone deficiency.

The pharmacokinetics (PK) of methionyl GH (metGH) were characterized in 20 newly diagnosed GH-deficient children (19 males; 12.9 +/- 3.3 yr old; initial height, 138.8 +/- 16.2 cm; weight, 32.1 +/- 13.1 kg) after the first dose (FD) of metGH and again after 4-5 weeks of multiple dosing (MD). All subjects received a total metGH dose of 0.3 mg/kg.week by sc administration, but were randomized to receive the drug daily (D; n = 12; dose, 0.043 mg/kg) or three times per week (TIW; n = 8; dose, 0.1 mg/kg). After drug administration, repeated blood samples (n = 14) were obtained over a 10-h period. Concentrations of metGH from each sample were determined using a monoclonal antibody radiometric assay (range of linearity, 0.5-40.0 ng/ml; coefficient of variation, less than 4%). Plasma concentration vs. time data were curve fit using a nonlinear weighted least squares algorithm which permitted calculation of the following PK parameters (mean +/- SEM; FD vs. MD group): elimination rate constant (0.23 +/- 0.04 vs. 0.25 +/- 0.04 h-1), absorption rate constant (0.43 +/- 0.05 vs. 0.48 +/- 0.04 h-1), elimination half-life (t1/2; 3.01 vs. 2.77 h), total plasma clearance (CL/F; 0.32 +/- 0.02 vs. 0.54 +/- 0.09 L/h.kg), and apparent volume of distribution (VDss/F; 2.2 +/- 0.14 vs. 3.15 +/- 0.28 L/kg). Both the CL/F and VDss/F of metGH were significantly greater when data from the entire study population were compared on the basis of FD vs. MD administration. With the exception of a larger VDss/F in subjects who received daily (3.6 +/- 0.4 L/kg) vs. TIW metGH (2.4 +/- 0.2 L/kg), no significant differences were found for the PK parameters between the D and TIW dosing groups. In all subjects, absorption of metGH was slow, with an average time to reach maximum concentration (Tmax) of 4.4 h and an absorption t1/2 that ranged from 1.4-1.8 h. Proportionality was also found between the dose and the area under the plasma concentration vs. time curve, suggesting dose-independent PK of metGH. Our data demonstrate that the PK of metGH after sc administration to children are markedly different from those previously reported in adults and, also, do not vary as a consequence of dosing schedule (i.e. D vs. TIW). The apparent increase in CL/F and VDss/F for met GH with multiple dosing may reflect concentration-dependent changes in plasma binding of the drug or, alternatively, represent the effect of increased body mass on the pharmacokinetics of GH.

Adolescent↗
PubMed1991

Glomerulopathy in patient with Donohue syndrome (leprechaunism).

OBJECTIVE: To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. RESEARCH DESIGN AND METHODS: The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. RESULTS: On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. CONCLUSIONS: This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen.

Adolescent↗
PubMed1990

Effects of dideoxyforskolin on proteoglycan synthesis and structure in embryonic chick chondrocyte cultures.

1,9-Dideoxyforskolin inhibits proteoglycan synthesis and xyloside-initiated glycosaminoglycan (GAG) synthesis in chick embryo chondrocytes. Dideoxyforskolin does not affect the length of xyloside-initiated GAG chains secreted into the medium but chains from the dense proteoglycan secreted into the medium appear slightly longer. Incorporation of labeled serine into the dense proteoglycan and subsequent digestion with Pronase revealed a dramatic decrease in percent of total radioactivity associated with GAG chains in the proteoglycan from cultures treated with forskolin or dideoxyforskolin. These observations suggest that these diterpenes have a specific inhibitory effect on chain initiation reactions and thus may be useful tools in the study of proteoglycan synthesis and processing.

Animals↗
PubMed1990

Effect of forskolin on synthesis of xyloside-initiated glycosaminoglycans in embryonic chick chondrocytes.

The synthesis of sulfated glycosaminoglycan (GAG) chains has been studied in the presence of various concentrations of the artificial acceptor 4-methylumbelliferyl beta-D-xyloside and of forskolin. Sulfated GAG chains formed in the presence of forskolin had a smaller hydrodynamic radius than controls, as revealed by chromatography on Sepharose CL-6B. Sulfated GAGs from both control and treated cultures behaved identically when chromatographed on DEAE.

Animals↗
PubMed1990

Effect of glycated albumin on phenytoin binding in elderly patients with type II diabetes mellitus.

We evaluated the effect of glycated albumin on phenytoin protein binding in 36 elderly (age range 63-94 yrs) patients with type II diabetes mellitus (DM) under diet management. Serum was spiked with 15 mg/L phenytoin and incubated. A serum ultrafiltrate was obtained from each sample for determining total and free phenytoin concentrations. Glycated hemoglobin was determined by boronate-affinity chromatography, and glycated albumin was separated from nonglycated fractions with boronate-agarose gel. Glycated hemoglobin in the study group ranged from 4.3-14.6% (mean 7.8 +/- SD 2.1%) and glycated albumin ranged from 3.7-12.5% (7.4 +/- SD 2.6%). We observed no correlation between glycated albumin and the percentage of free phenytoin (r2 = -0.14; p = 0.419). The concentration of nonglycated albumin ranged from 0.66-4.28 g/dl (mean 3.45 +/- 0.67 g/dl) and was calculated from measured total and glycated albumin concentrations. A correlation between the free fraction of phenytoin and nonglycated albumin was not demonstrated (r2 = 0.22, p = 0.22). In addition, a correlation was not observed between total glycated albumin and the free fraction of phenytoin (r2 = -0.095; p = 0.58). We conclude that elderly patients with type II DM under diet control do not have significant alterations in phenytoin protein binding. The use of total serum phenytoin levels therefore appears appropriate for determining phenytoin dosages in elderly patients with well controlled type II DM.

Aged↗
PubMed1989

Metabolic effects of forskolin in chick chondrocytes.

The effects of forskolin on parameters of energy metabolism and proteoglycan synthesis have been investigated in chick embryo sternal chondrocyte cultures. After 8 h exposure to 100 microM forskolin, ATP levels and oxygen consumption were unaltered. Protein synthesis was unaffected up to 50 microM forskolin and protein degradation was unaffected by forskolin up to 100 microM. In contrast, incorporation of the proteoglycan precursors, 35SO4 and [3H]glucosamine, was more sensitive to forskolin. Inhibition was linear with dose between 10 and 100 microM, reaching 70% at 100 microM. Incorporation of 35SO4 into glycosaminoglycan chains initiated on an artificial beta-xyloside acceptor was inhibited in the same manner. cAMP accumulation was maximal at 10 microM forskolin, a concentration which did not alter proteoglycan synthesis. We conclude that a major, acute effect of forskolin in these short-term experiments is inhibition of proteoglycan synthesis in a cAMP-independent manner.

Adenosine Triphosphate↗
PubMed1988

Protein binding of phenytoin and lidocaine in pediatric patients with type I diabetes mellitus.

We evaluated serum protein binding of phenytoin and lidocaine, the extent of albumin and hemoglobin glycation, and alpha-1-acid glycoprotein concentrations in 47 children and adolescents (9-17 years) with type I diabetes mellitus (DM). Serum was incubated with phenytoin (n = 47) and lidocaine (n = 32) to yield total concentrations of 19.4 +/- 1.34 and 4.6 +/- 0.5 mg/l, respectively. A serum ultrafiltrate was prepared from an aliquot of each sample by membrane centrifugation. Total and free concentrations of phenytoin (free fraction 8.3 +/- 1.0%) and lidocaine (free fraction 25.8 +/- 11.6%) were determined using a fluorescence polarization immunoassay technique. A linear relationship (r = 0.63, p = 0.0001, y = 40.1 + [-0.2x]) was also found between the alpha-1-acid glycoprotein concentration (68.5 +/- 20.9 mg%, range 47.2-134.7 mg%) and lidocaine-free fraction (n = 32). No relationship existed between the extent of glycated albumin and the lidocaine-free fraction, in contrast to the linear correlation (r = 0.49, p = 0.0005, y = 3.7 + 0.4x) found between the extent of glycated albumin and the free fraction of phenytoin in serum (n = 47). A similar correlation (r = 0.49, p = 0.014, y = 3.7 + 0.3x) was found between glycated albumin (%) and the phenytoin-free fraction (3.9 +/- 0.9%) when examined in a separate (n = 17) set of patient samples spiked to contain a total serum phenytoin concentration of 32.6 +/- 1.4 (range 29.4-35.7) mg/l. Our data demonstrate a predictable increase in the free fraction of phenytoin as the extent of albumin glycation increases in pediatric patients with type I DM who are in poor glycemic control. This relationship was not found for lidocaine, a representative basic compound. These findings suggest that glycation of albumin alters the binding of phenytoin in children and adolescents with type I DM.

Adolescent↗
PubMed1988

Effects of IGF-I on the synthesis and processing of glycosaminoglycan in cultured chick chondrocytes.

We have studied the effect of the somatomedin IGF-I on stimulation of synthesis of DNA, RNA, protein, and glycosaminoglycan in chick chondrocytes. Stimulation of RNA and protein synthesis was rapid, occurring within 10 min after addition of IGF-I. Stimulation of sulphation required a lag time of about 2 h, whether chains were initiated on native protein core or on the artificial acceptor 4-methyl-umbelliferyl-beta-D-xyloside. DNA synthesis was not stimulated until after 10 h of exposure to IGF-I. Investigation of the rate of processing of proteoglycan core protein after pulse-labelling chondrocytes with 35SO4 yielded data which were best described by a biexponential function. IGF-I had no effect on the t 1/2 of the initial phase (16.44 min in the absence of IGF-I and 20.38 min in the presence of IGF-I). However, addition of IGF-I resulted in a decrease in the t 1/2 of the terminal phase from 122.58 to 55.44 min, which may reflect an increase in synthesis in the enzymes necessary for polymerization and sulphation of proteoglycan.

Aggrecans↗
PubMed1987

Isolation of a biotin receptor from hepatic plasma membranes.

Biotin, one of the growth promoting members of the B complex vitamin family, was found in the present investigation to have a specific receptor on isolated plasma membranes. Biotin bound to its receptor in a linear manner at 20 degrees C with some binding as early as 30 minutes and full equilibrium binding being present at 20 hours. The best binding was found at 0.6 mg/ml of protein, but significant binding was still present at 0.6 microgram/ml. The saturation of ligand binding sites was at 10(-7)M. Half maximal saturation of binding was between 10(-9) and 10(-10)M. These results demonstrate that a receptor for biotin does exist on purified plasma membranes.

Animals↗
PubMed1987

Resistance to the effects of thyroid hormone in children.

We have described three children with serum levels of TSH that are too high for the concomitant serum T4 level. Two of them meet the criteria for combined central and peripheral resistance to thyroid hormone. The third has long-standing central resistance to TSH suppression previously reported in congenital hypothyroidism. The recognition of this syndrome by physicians is important to avoid unnecessary and potentially dangerous treatment.

Child↗
PubMed1987

Alteration of phenytoin binding by glycosylation of albumin in IDDM.

We measured glycosylated albumin and hemoglobin and serum protein binding of phenytoin in 57 children and adolescents with insulin-dependent diabetes mellitus (IDDM). Serum was incubated with phenytoin to yield concentrations of 15 and 25 mg/L, and a serum ultrafiltrate was prepared from an aliquot of each sample. We observed a linear correlation between glycosylated albumin and the free fraction of phenytoin at serum phenytoin concentrations of 15 mg/L (r = .35, P = .03) and 25 mg/L (r = .40, P = .003). A better correlation existed between the free fraction of phenytoin and total albumin concentrations for both serum concentrations (r = .45, P = .005 for 15 mg/L; r = .56, P = 10-5) for 25 mg/L), whereas the best linear correlation resided between the free fraction of phenytoin and the concentration of nonglycosylated albumin (r = .54, P = .0005 for 15 mg/L; r = .63, P less than 10(-6) for 25 mg/L). There was no correlation between the free fraction of phenytoin and the concentration of glycosylated albumin. Incubation of solutions of glycosylated and nonglycosylated albumin demonstrated significantly lower binding to the glycosylated fraction (P = 8.1 X 10(-6)). These results indicate that glycosylation of albumin diminishes the affinity of the phenytoin binding site on albumin. This alteration may have clinical significance in that it may alter the disposition of phenytoin in patients with IDDM and produce free phenytoin serum concentrations that are not accurately reflected by total serum phenytoin concentrations.

Adolescent↗
PubMed1986

Decreased cyclic guanosine 3',5' monophosphate and guanylate cyclase activity in leprechaunism: evidence for a postreceptor defect.

Patients with leprechaunism have hyperinsulinemia and extreme insulin resistance. The mechanism of the insulin resistance has not been delineated. To examine postreceptor events in this unusual syndrome we have assayed the enzyme guanylate cyclase [E.C.4.6.12], which is modulated by insulin, and the concentration of the intracellular messenger cyclic GMP in liver from two children with leprechaunism and extreme insulin resistance. Both patients exhibited down regulation of the red blood cell insulin receptors, but normal insulin receptor binding to Ebstein-Barr transformed IM-9 lymphocytes and monocytes. There was no evidence of antireceptor or antiinsulin antibodies. Activity of liver guanylate cyclase expressed as pmol/mg protein/10 min incubation in the soluble and particulate fractions were, respectively, Ark-1 133 +/- 18, 25 +/- 6; Ark-2 129 +/- 17, 23 +/- 8; control children (six average) 287 +/- 16, 55 +/- 9. The concentration of cyclic GMP was also 50% lower (0.08 +/- 0.03 in Ark-1 and 0.07 +/- 0.04 in Ark-2), compared to 0.19 +/- 0.07 pmol/mg protein/min in the control livers. There was no change in adenylate cyclase activity in children with leprechaunism versus the control children. These data suggest an abnormality of a postreceptor event in this rare genetic disease. These data, however, do not rule out that in some cases of leprechaunism a receptor binding abnormality may be the primary defect. We speculate that a defect in insulin action distal to plasma membrane receptor binding may be etiological in this unusual syndrome.

Abnormalities, Multiple↗