Biomedical subjects
Publications and source records attributed to A L Rosenbloom.
Specific and nonspecific [125I]insulin binding and concentration of unlabeled hormone producing 50 percent competition with 1.0 nanomolar [125I]insulin for specific binding sites correlated positively with age of fibroblast donors. Cells from four children with precocious aging--three with progeria and one with Rothmund syndrome-resembled those from the chronologically old.
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The concentration of reducing sugar in the urine is commonly used in the management of diabetes in children. Supplemental doses of regular insulin are administered in response to the concentration of urine sugar according to a protocol termed the "sliding scale." This practice assumes that the concentration of sugar in urine is a good indicator of the plasma glucose concentration. This assumption was tested by comparing urine sugar concentrations in first and second voided urines with the plasma glucose concentrations in 220 children with diabetes. The correlation was good (r = .92) for both the first and second voided urine specimens. Thus, urine sugar concentrations in general define the level of plasma glucose. The large standard deviation of the plasma glucose at each concentration of urine sugar, however, limits the usefulness of urine sugar as an accurate reflection of the coincident plasma glucose concentration. The urine sugar concentration, although useful for the general management of diabetes, provides significant risk when used to guide frequent adjustments in insulin administration. Therefore, the "sliding scale" should not be used in the treatment of children with diabetes.
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Clinical and laboratory evaluations are reported on two patients with congenital goiter and hypothyroidism due to iodide organification defect. In one patient, a 31-year-old white male with severe mental retardation, administration of perchlorate caused discharge of 69% of the radioiodine accumulated in the thyroid gland. Thyroid tissue had negligible peroxidase activity in the tyrosine-iodinase, triliodide, and guaiacol assays. Preincubation of subcellular fractions with hematin restored activity. The restored enzyme was labile to high concentrations of H2O2 (5.6times 10-4 h2o2 produced inhibition in the triiodide assay). Heating of the enzyme for 5 min at 46 degrees C produced 50% inactivation, while higher temperatures were required to half-inactivate normal peroxidases. This case represents a second example of the "peroxidase apoenzyme-prosthetic group defect" causing congenital goiter. The second patient, an example of the "deficient peroxidase defect," was a 10-yr-old girl with 35% discharge of thyroidal radioiodine by perchlorate. Peroxidase activity in the goiter tissue was quantitatively decreased (10%-20% of normal values) but kinetically normal with respect to apparent Km for H2O2. Hematin had little effect on the enzyme. Peroxidase activity had abnormal subcellular distribution, since pellets sedimenting between 39,000 and 105,000 g contained most of the activity. Normal thyroglobulin was observed in the thyroid gland of the patient. Two distinct defects of the peroxidase system can produce congenital goiter by limiting organification of iodide.
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The Gainesville Youth Clinic was organized to meet a community need for medical care of nonuniversity youth and to provide experience in adolescent medicine to pediatric house officers. Demographic and clinical data were gathered in three studies spanning the first 15 months of operation. The clinic sees 2,200 patients (3,000 visits) annually; two thirds are girls, 98% are white, and 90% are 15 to 25 years old. The population was not predominantly transient; parental occupations were mostly professional or skilled. Educational level was consistent with age; one third of the patients are students at present. Genitourinary problems, principally venereal infection, account for nearly one third of all visits and suspected pregnancy or birth control another one fourth. The clinic experience has emphasized the youth cultural influences on health, increased the participant's insight into the emotional turmoil of adolescence, and has suggested a style and design for providing primary care to this population consistent with the academic objectives of a pediatric department.
Proinsulin levels (PLC) in serum were determined after gel filtration on specimens obtained during oral glucose tolerance testing (OGTT) in seven patients with repeated abnormality in OGTT and in a group of seven control subjects matched for age. Fasting and thirty-, sixty-, and 120-minute postglucose venous samples were analyzed for glucose (PG) and immunocreactive insulin (IRI) as well as PLC, PG and IRI mean concentrations were greater at all testing times in the patient population, but the mean IRI/PG was significantly higher in the patients only at fasting. PLC mean levels were higher in the patients but not to a level of significance. Percentage of total IRI atributable to PLC at each time point was identical between the two groups. The apparcent diminished effectiveness of circulating insulin in chemical diabetes cannot be attributed to an abnormal proportion of proinsulin.
This report analyzes age-specific glucose (PG) and immunoassayable insulin (IRI) responses during oral glucose tolerance testing (OGTT) and examines test results in children and adolescents with OGTT abnormality using the age-appropriate control data. Controls' (n = 93) and patients' (n = 63) results were compared on the basis of statural age (SA) at the time of testing. Control tests (n = 101) showed significant positive correlation of fasting and four-hour postingestion PG with SA (p less than 0.001), but mean area under the PG curves did not vary between the SA groups (I--18.69 months, II--70-131 months, III--132+ months). The absence of differences of other sampling times permits uniform diagnostic criteria for this age group. IRI was positively correlated with SA at all testing times, and mean levels differed significantly between each SA group at every sampling time; the mean areas under the IRI curve also differed significantly between SA groups as did the mean ratios of IRI area to PG area (group I--0.2639 +/- 0.0175 S.E.M., group II--0.3864 +/- 0.0235, group III--0.6262 +/-0.0491). Patient tests (n = 110) were separated into normal (N), borderline (B), and chemical-diabetic (C) for each SA group. IRI means were above control data for each test type in each SA group at all sampling times; one fourth of these differences were significant. IRI responses also increased within each SA group from N to B to C tests. Mean IRI areas and IRI area to PG are mean ratios were higher than in controls, and this difference was greatest with the most abnormal (C) test type in each SA group. A subgroup of three patients who had low IRI responses from the outset and developed overt diabetes in one to three years was excluded from the analysis. In contrast to apparent relative insulin inefficiency with normal maturation and with chemical diabetes, they had exceptional responsiveness to their low IRI levels. Variable involvement of alpha as well as beta cells in the pathophysiology of diabetes is suggested as one explanation for these paradoxic observations. Changing receptor affinity might also be implicated.
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Two teenage patients, who had severe psychosocial problems that complicated their diabetes management, were treated for one month (14-year-old girl) and two months (16-year-old boy) by frequent pulses of insulin injected subcutaneously by a portable, programmed pump. Additional pulses were manually adjusted by the patient before eating. Both patients experienced improved sense of well-being, marked reduction in urine volume and in glycosuria, and reduced glycemic excursions and average levels. The boy had accelerated linear growth and a decreas in HbA1 percentage. Despite marked clinical improvement, permitting return to school, the girl was impelled to interrupt pump administration after two weeks. Both patients continue to use the device voluntarily; a smaller unit, however, that doesn't have the conspicuous external controls, would likely be readily acceptable to most young patients.