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Biomedical subjects

J M Gertner

Publications and source records attributed to J M Gertner.

At least 73 records · Page 4Linked to original sources
PubMed1984

The effect of small but sustained elevations in circulating growth hormone on fuel metabolism in growth hormone deficiency.

Although growth hormone (GH) concentrations are not always pathologically elevated in patients with acromegaly, it has been suggested that the metabolic and somatic consequences of this condition may be due to a loss of the normal episodic secretion of GH. To examine the effects of maintaining modest but constant levels of circulating GH, we administered continuous subcutaneous infusions of growth hormone (CSIGH) to eight previously untreated GH-deficient children (6-19 yr). CSIGH given for 90 h in doses equivalent to the standard dose for replacement therapy, raised mean serum GH levels from less than 3.0 to 5.9 +/- 1.0 ng/ml. In comparison, 24-h mean GH levels in five normal adolescents averaged 10.1 +/- 1.5 ng/ml. As expected, however, normals showed much more variability in GH concentration. The constant elevations in serum GH levels achieved with CSIGH produced significant impairment of oral glucose tolerance. During CSIGH, plasma glucose concentrations 60-120 min after oral glucose loading were 30-40 mg/dl higher than corresponding pre-infusion values (P less than 0.01). This impairment of oral glucose tolerance during CSIGH occurred despite a doubling of the area under the insulin/time curve after oral glucose (P less than 0.02 versus pre-infusion area). Indeed, plasma insulin levels after oral glucose in patients on CSIGH exceeded those observed in normal controls, suggesting that CSIGH had induced a degree of insulin resistance. There was a transient increase in plasma free fatty acid levels on the first day of CSIGH. Somatomedin-C concentration remained unchanged in four of six patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1984

A consideration of the hormonal basis and phosphate leak hypothesis of absorptive hypercalciuria.

Fifty patients with absorptive hypercalciuria (AH), 25 normal subjects (NS), and 25 nonhypercalciuric patients with stone disease (NHSF) were studied using an oral calcium tolerance test and 24-h urine collections on both a restricted and an unrestricted calcium intake. Mean (+/- SD) fasting fractional calcium excretion was increased in the patients with AH (2.7 +/- 1.1% vs. 1.4 +/- 0.6% in the NS; P less than 0.001) and was negatively correlated with fasting nephrogenous cAMP, suggesting that this renal calcium leak was secondary to parathyroid suppression. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] was elevated in 80% of patients with AH and was high normal in the remaining 20%. Ten patients, selected on the basis of results for 1,25-(OH)2D greater than 4 SD from the normal mean, displayed a particularly severe pattern of abnormalities, including mild hypercalcemia in two patients. Pooled data from the NS and patients with AH revealed a significant negative correlation between the plasma concentration of 1,25-(OH)2D and the renal phosphate threshold (r = -0.40; P less than 0.001), but this correlation lost significance when the NHSF were substituted for the NS as a control group (r = -0.07; P = NS). These findings 1) provide a pathophysiological basis for the increase in fasting calcium excretion commonly observed in hypercalciuric patients, and 2) stress the importance of circulating 1,25-(OH)2D in the pathogenesis of the syndrome, but 3) fail to support the phosphate leak theory of pathogenesis.

Adult↗
PubMed1984

An experimental human model of 1,25-dihydroxyvitamin D-mediated hypercalciuria.

An increase in fasting calcium excretion occurs in hypercalciuric patients and has been interpreted by many investigators as evidence for a primary renal tubular leak of calcium. In a recent series of 50 patients with absorptive hypercalciuria, we found a mean increase in fasting fractional calcium excretion (calcium clearance) and provided data suggesting that this leak of calcium was secondary to intestinal hyperabsorption of calcium and suppression of parathyroid secretion. To examine this question, a model of 1,25-dihydroxyvitamin D [1,25-(OH)2D]-mediated hypercalciuria was created by administering a large dose of 1,25-(OH)2D to normal subjects. In addition to the expected features of absorptive hypercalciuria during 1,25-(OH)2D administration, the subjects had an increase in fasting calcium excretion and a marked increase in calcium excretion during a restricted calcium diet, points that might be interpreted as favoring a resorptive and/or renal component to the net hypercalciuria. However, total hydroxyproline excretion remained unchanged (18.0 vs. 19.0 mg/g creatinine), and the increase in fasting calcium excretion was found to reflect an increase in calcium clearance; the latter was inversely correlated with parathyroid function, as determined by fasting measurements of nephrogenous cAMP excretion (r = -0.77; P less than 0.01). We conclude that measurements of calcium excretion in the fasting state or on a restricted calcium diet do not represent valid criteria for differential diagnosis of the hypercalciurias.

Adult↗
PubMed1984

Effect of diabetes and its control on insulin-like growth factors in the young subject with type I diabetes.

The influence of diabetes and its control on circulating levels of growth hormone and growth hormone-dependent, insulin-like growth factors (IGF) remains controversial. In the present study, the effect of a 1-wk period of intensive insulin therapy on growth hormone and IGF I and II has been determined in 19 young (age 13-22 yr), insulin-dependent (type I) subjects with diabetes mellitus. IGF I was low during conventional insulin therapy (198 +/- 20 versus 438 +/- 38 ng/ml in nondiabetic subjects, P less than 0.001), and rose within the week of intensified treatment (to 255 +/- 15 ng/ml, P less than 0.005), concomitant with a reduction in plasma glucose from 233 +/- 16 to 110 +/- 5 mg/dl. IGF I rose despite a significant fall in mean 24-h growth hormone levels from 14.1 +/- 2.2 to 9.0 +/- 1.2 ng/ml (P less than 0.02). The mean IGF II value for the diabetic subjects (504 +/- 39 ng/ml) was not significantly different from that of the nondiabetic control group (506 +/- 30 ng/ml, P greater than 0.3) and was not altered by intensified therapy. However, four individual patients with very low IGF I also had depressed IGF II (248 +/- 16 ng/ml), which was corrected (to 377 +/- 35 ng/ml) with improved metabolic control. These data suggest that elevated growth hormone levels in poorly controlled diabetes are ineffective in IGF I generation and that this defect is at least partially corrected by acute improvement in control. The rise in IGF I levels accompanying intensive insulin treatment may suppress the excessive secretion of growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Pituitary response to growth hormone-releasing factor in diabetes. Failure of glucose-mediated suppression.

To evaluate the mechanism underlying raised growth hormone levels in diabetes, we compared the response to growth hormone-releasing factor (GRF) in type I diabetic and healthy control subjects. In 12 poorly controlled diabetic subjects (fasting plasma glucose 276 +/- 27 mg/dl) basal serum growth hormone levels were elevated by 200-300% (P less than 0.02), yet the incremental increase in growth hormone after GRF injection was no greater than in control subjects. Furthermore, five additional diabetic subjects with normal growth hormone levels after long-term insulin pump treatment also showed an identical response to GRF. Thus, raised basal growth hormone levels in diabetes and the fall that follows intensive insulin treatment may reflect changes in hypothalamic regulation of, rather than in pituitary responsiveness to, GRF. However, when five normal subjects were restudied during glucose infusion, even quite modest hyperglycemia (plasma glucose approximately 150 mg/dl) caused marked suppression of the response to GRF (P less than 0.005). Thus, the "normal" response to GRF in poorly controlled diabetes is actually inappropriate. Failure of the pituitary to suppress in response to hyperglycemia in diabetes implies a second abnormality that may further aggravate disordered growth hormone secretion.

Adolescent↗
PubMed1983

Impaired phosphorus conservation and 1,25 dihydroxyvitamin D generation during phosphorus deprivation in familial hypophosphatemic rickets.

The pathogenesis of familial hypophosphatemic rickets (FHR) is incompletely understood. We therefore examined the effects of acute dietary phosphorus deprivation to see whether renal phosphate conservation and increased 1,25 dihydroxyvitamin D [1,25(OH)2D] plasma levels, which normally follow restriction of phosphorus intake, could be induced in patients with FHR. Six healthy male volunteers (age 26 +/- 3 yr) and seven male patients with FHR (age 24 +/- 3 yr) were placed on a low phosphorus diet supplemented with aluminum hydroxide and studied over a 4-d period. The patients with FHR excreted more than five times as much phosphorus per day at the conclusion of the study than did the controls (176 +/- 61 mg/24 h vs. 33 +/- 11 mg/h). In the normal subjects, maximum tubular reabsorptive capacity for phosphorus/glomerular filtration rate (TmP/GFR) rose progressively during phosphorus deprivation, and the rise from base line was more than two times greater than that seen in patients with FHR. Immunoreactive parathyroid hormone levels and nephrogenous cyclic AMP were initially normal in both groups and no change was seen in either group with phosphorus deprivation. In the normal subjects, 1,25(OH)2D levels rose progressively over the 96 h of the study (49 +/- 3 to 63 +/- 6 pg/ml, P less than 0.05), while mean circulating 1,25(OH)2D in the patients with FHR did not change (34 +/- 3 to 29 +/- 3 pg/ml). The changes in individual plasma 1,25(OH)2D levels correlated strongly with the change in individual nephrogenous cyclic AMP measurements in the patients with FHR (r = +0.93), while no such correlation was observed in the normal subjects. These data demonstrate a defective renal response to phosphorus deprivation in patients with FHR including a qualitatively abnormal response in 1,25(OH)2D generation.

Absorption↗
PubMed1983

Increased bone turnover with decreased bone formation by osteoblasts in children with osteogenesis imperfecta tarda.

Iliac crest bone biopsies from nine children (6-15 yrs old) with osteogenesis imperfecta tarda (OI) have been studied by bone histomorphometry after double fluorescent labeling with tetracycline and compared to five unlabeled biopsies from normal children in the same age group. The results indicate that children with OI have a low trabecular bone volume associated with an increased bone turnover rate. Bone formation is increased at the tissue level despite a decrease in the activity of individual osteoblasts. The original defects in OI seems, therefore, to be in the rate of matrix synthesis by osteoblasts. It is, however, compensated by an increase in the number of these cells. These results suggest that these children were not losing bone at the time of the biopsy, which fits with the clinical stability of OI with age. Our study therefore suggests that the osteopenia observed in OI is most likely due to an inability to accumulate bone during growth, as normal children do, rather than to a progressive net loss of bone.

Adolescent↗
PubMed1983

A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism.

Recent studies have emphasized the pathophysiological importance of circulating 1,25-dihydroxyvitamin D ((1,25-(OH)2D] in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. Reasoning that phosphate administration might be capable of reducing the plasma concentration of 1,25-(OH)2D in patients with a prominent 1,25-(OH)2D-mediated absorptive component to their disease, 10 carefully selected patients were treated with oral phosphate (1500 mg elemental phosphorus daily) for 1 yr. Phosphate treatment significantly reduced circulating 1,25-(OH)2D levels (84 to 56 pg/ml), the calciuric response to an oral calcium tolerance test (0.30 to 0.21 delta mg calcium/dl GF), and calcium excretion on an unrestricted calcium diet (438-269 mg/day), in essence reversing the absorptive pattern of abnormalities observed before treatment. This response, however, was accompanied by an increase in biochemical hyperparathyroidism, as assessed by circulating immunoreactive PTH and nephrogenous cAMP excretion. In patients with biochemical evidence of an increase in bone resorption before therapy, histomorphometric, radiographic, and biochemical data revealed a trend toward a reduction in bone turnover during phosphorus therapy, with an apparent maintenance of coupled bone resorption and bone formation. This trend, however, was of marginal statistical significance in the patient group as a whole. It is concluded 1) that phosphate therapy represents a viable medical alternative in selected patients with primary hyperparathyroidism, 2) that the net response in treated patients is multifaceted and complex, and 3) that the efficacy of phosphate therapy will ultimately depend upon its long term effects on skeletal homeostasis.

Bone and Bones↗
PubMed1981

Vitamin D deficiency rickets as a late complication of the short gut syndrome during infancy.

Four infants with less than 35 cm of jejunum and ileum remaining following neonatal operations and after being weaned from long-term total parenteral nutrition onto an "elemental" formula, developed the syndrome of vitamin D deficiency rickets at 9-15 mo of age. The diagnosis of rickets was confirmed by biochemical and radiographic findings. Serum 25 hydroxy vitamin D (25 OHD) values were significantly lower than normal and oral 25 OHD absorption studies indicated severe vitamin D malabsorption. This report emphasizes the importance of prospective assessment of all neonates having distal ileal resection to detect the early stages of vitamin D deficiency rickets.

25-Hydroxyvitamin D 2↗
PubMed1980

XY gonadal dysgenesis associated with the congenital nephrotic syndrome.

The occurrence of a nephrotic syndrome in a female infant with a 46,XY karyotype is reported. The internal genitalia were female but a microscopic region of immature testicular tissue was present in 1 of 2 streak gonads. The relationship of this child's abnormal genital differentiation to her renal disease is discussed in the light of reported cases of infantile nephritis and Wilms' tumor in male pseudohermaphrodites. It is suggested that a common teratogen operating on the embryonic urogenital ridge may cause both genital and renal anomalies.

Female↗
PubMed1980

Effect of dietary phosphate on transport properties of pig renal microvillus vesicles.

Dietary phosphate manipulation results in stable adaptive changes in the transport functions of microvillus membrane vesicles isolated from pig renal cortex. When assayed under sodium gradient conditions, phosphate uptake is enhanced 200--400% in vesicles prepared from animals maintained on a low-phosphate diet (0.22%) compared to high-phosphate diet controls (0.82%). When transport is assayed in sodium preequilibrated vesicles, a 100% enhancement of phosphate uptake is demonstrable. Stimulation of phosphate uptake into low-phosphate diet vesicles after the imposition of a sodium chloride gradient is equivalent if uptake is measured at pH 6.0 or 8.0 and can be kinetically characterized as resulting from a Vmax alteration in the phosphate transport system. Microvillus membrane vesicle phosphate transport is maximally stimulated after only 2 days of dietary deprivation. Although a longer period (1 and 2 wk) of phosphate restriction does not further stimulate phosphate transport, it does result in an inhibtion of other sodium gradient-dependent transport systems (glucose, alanine).

Animals↗
PubMed1979

[Urinary excretion of cAMP after PTH injection in patients with hypohyperparathyroidism (author's transl)].

The urinary excretion of cyclic adenosine monophosphate (cAMP) and phosphate in response to an intravenous injection of 200 U.I. PTH in two women with hypohyperparathyroidism was studied. PTH activity was previously verified. Both patients were under treatment with vitamin D and their plasma calcium and phosphate levels were normal at the time of the study. Basal values for urinary excretion of cAMP were 2.25 nmol/min in one patient and 4.2 nmol/min in the other. Maximum excretion after PTH injection were 6.4 nmol/min and 5.5 nmol/min respectively. Basal values for urinary excretion of phosphate were 0.32 mg/min in the first patient and 0.18 mg/min in the second. After PTH injection the peak values were 0.73 mg/min and 0.35 mg/min respectively. These results pointed out the existence of a renal resistance to PTH which, unlike what happens in other similar patients, cannot be corrected with the administration of vitamin D.

Cyclic AMP↗