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Biomedical subjects

G B Pehling

Publications and source records attributed to G B Pehling.

8 recordsLinked to original sources
PubMed2001

A novel inborn error in the ligand-binding domain of the vitamin D receptor causes hereditary vitamin D-resistant rickets.

Mutations in the vitamin D receptor (VDR) cause hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disease resulting in target organ resistance to 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. In this report, we describe the clinical case and molecular basis of HVDRR in an Asian boy exhibiting the typical clinical features of the disease including alopecia. Using cultured dermal fibroblasts from the patient, 1,25(OH)(2)D(3) resistance was demonstrated by a shift in the dose response required for 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) mRNA induction. Western blot showed that the cells express a normal size VDR but contained reduced levels of receptor compared to normal cells. At 24 degrees C, the affinity of the patient's VDR for [(3)H]1,25(OH)(2)D(3) was 50-fold lower than the VDR in normal fibroblasts. Sequence analysis identified a unique T to G missense mutation in exon 6 that changed phenylalanine to cysteine at amino acid 251 (F251C). The recreated F251C mutant VDR showed reduced transactivation activity using a 24-hydroxylase promoter-luciferase reporter. Maximal transactivation activity exhibited by the WT VDR was not achieved by the mutant VDR even when the cells were treated with up to 10(-6) M 1,25(OH)(2)D(3). However, the transactivation activity was partially rescued by addition of RXRalpha. In the yeast two-hybrid system and GST-pull-down assays, high concentrations of 1,25(OH)(2)D(3) were needed to promote F251C mutant VDR binding to RXRalpha, indicating defective heterodimerization. In conclusion, a novel mutation was identified in the VDR LBD that reduces VDR abundance and its affinity for 1,25(OH)(2)D(3) and interferes with RXRalpha heterodimerization resulting in the syndrome of HVDRR.

Animals↗
PubMed1993

Delayed recovery from post-thyroidectomy hypoparathyroidism: a case report.

Thirteen hours after a subtotal thyroidectomy was performed for hyperthyroidism, a patient developed carpopedal spasms, parathesias and hypocalcemia to 6.9 mg/dL. After initial stabilization with intravenous calcium administration, oral calcium carbonate and calcitriol were required. Ten months postoperatively serum calcium levels rose and supplementation was gradually discontinued. The serum parathyroid hormone (PTH) level was 1.0 pg/mL on the second postoperative day and levels were undetectable despite sensitive testing 3 months later (normal 10-65 pg/mL). Two years after surgery, the PTH level has increased to 36 pg/mL, but remains relatively low considering the patient's continued mild hypocalcemia. To our knowledge, there has been no previously reported case of long-term post-thyroidectomy hypocalcemia documenting undetectable parathyroid function and subsequent spontaneous improvement. This case suggests that delayed recovery of parathyroid function and discontinuation of vitamin D and calcium supplementation may be possible in some post-thyroidectomy patients with hypocalcemia due to severe hypoparathyroidism.

Adult↗
PubMed1990

Adrenal insufficiency secondary to adrenal hemorrhage. Two case reports and a review of cases confirmed by computed tomography.

We report two cases of adrenal hemorrhage and review 17 others that were confirmed by hormone measurements and computed tomography. Precipitating factors included heparin therapy, surgery, hypotension, and sepsis. Heparin-associated thrombocytopenia may be an underappreciated cause of adrenal hemorrhage. Despite the availability of computed tomography, adrenal hemorrhage mimics many other diseases, and an early diagnosis remains difficult.

Adrenal Gland Diseases↗
PubMed1989

Adrenal insufficiency after operative removal of apparently nonfunctioning adrenal adenomas.

We describe a woman who developed adrenal insufficiency after removal of an apparently nonfunctional adrenal adenoma. She displayed no stigmata of Cushing's syndrome and had normal plasma and urinary cortisol levels. A second patient without clinical findings of Cushing's syndrome also had normal basal steroid levels. This patient displayed partial suppressibility with dexamethasone, had low-normal levels of serum corticotropin, and excreted a low concentration of urinary 17-ketosteroids. She also developed mild adrenal insufficiency after the operation. We believe the adrenal adenomas in these patients secreted enough cortisol to suppress the contralateral adrenal gland but not enough hormone to elevate basal steroid levels. Therefore, we suggest that all patients with adrenal masses be studied with the overnight dexamethasone suppression test rather than basal steroid hormone measurements to detect low levels of autonomous cortisol secretion. In addition, patients with adrenal masses that are not removed surgically should have serial adrenal function tests performed.

Adenoma↗
PubMed1985

Abnormal glucose modulation of islet A- and B-cell responses to arginine in non-insulin-dependent diabetes mellitus.

To assess the normality of islet A- and B-cell responses to a nonglucose secretogogue as well as the modulating effect of glucose in NIDDM, we examined plasma C-peptide and glucagon responses to arginine in eight patients with NIDDM and in six age- and weight-matched nondiabetic volunteers under conditions of identical hypoglycemia (approximately 70 mg/dl), euglycemia (94 mg/dl), and hyperglycemia (approximately 190 mg/dl). Plasma C-peptide responses to glucose and to arginine in the diabetic subjects were both significantly reduced at all glucose concentrations studied (P less than 0.01-0.005). The modulating effect of glucose on both islet A- and B-cell responses (slope of relation between plasma C-peptide or glucagon response versus plasma glucose concentration) was reduced greater than 80% in the diabetic subjects (P less than 0.01). We conclude that islet A- and B-cell responses to nonglucose secretogogues are abnormal in patients with NIDDM and that this may result from a functional defect in the modulating effect of glucose on insulin and glucagon secretion, which in some patients may be compensated for by hyperglycemia.

Arginine↗
PubMed1984

Abnormal glucose counterregulation after subcutaneous insulin in insulin-dependent diabetes mellitus.

We assessed glucose counterregulation during intensive insulin therapy in 20 patients with insulin-dependent diabetes mellitus (IDDM) by injecting therapeutic doses of regular insulin subcutaneously after overnight maintenance of euglycemia. As compared with nondiabetic controls matched for age and weight, 17 of the patients had more severe and more prolonged hypoglycemia (nadir, 42 +/- 2 in patients vs. 60 +/- 2 mg per deciliter in controls P less than 0.01; duration, 6.2 +/- 0.4 vs 2.1 +/- 0.6 hours, P less than 0.01). Most patients had decreased responses of several counterregulatory hormones. Marked rebound hyperglycemia (approximately equal to 300 mg per deciliter) ultimately developed in 11 patients. The only features distinguishing patients with rebound hyperglycemia from those without it were plasma free insulin concentrations during recovery from hypoglycemia (those with vs. those without, 7 +/- 1 vs. 22 +/- 2 microU per milliliter, P less than 0.01) and insulin-antibody binding (5 +/- 1 vs. 30 +/- 5 per cent, P less than 0.01). Rates of plasma glucose recovery from hypoglycemia were inversely correlated with plasma free insulin concentrations (r = -0.84, P less than 0.01); the latter in turn were directly correlated with insulin-antibody binding (r = 0.94, P less than 0.01). We conclude that many patients with IDDM have impaired glucose counterregulation due to multiple defects in counterregulatory-hormone secretion. This is associated with increased insulin-antibody binding, which prolongs the half-life of insulin. In such patients, intensive insulin therapy may be hazardous.

Adult↗
PubMed1984

Comparison of plasma insulin profiles after subcutaneous administration of insulin by jet spray and conventional needle injection in patients with insulin-dependent diabetes mellitus.

The characteristics of plasma free insulin profiles after conventional subcutaneous injection of regular insulin (10 units) and after jet injection of this amount of insulin were compared in eight subjects with insulin-dependent diabetes mellitus. Although administration of insulin with the jet injector resulted in peak plasma free insulin concentrations (45 +/- 4 microU/ml) similar to those achieved after conventional injection (47 +/- 5 microU/ml), it produced more rapid increases in plasma free insulin concentrations (time to peak concentration, 76 +/- 11 minutes versus 152 +/- 16 minutes; P less than 0.01) and less prolonged hyperinsulinemia. Variability in the peak insulin concentrations and the time to peak concentration was comparable for both methods of administration of insulin. Thus, insulin administered by jet injector may improve control of postprandial hyperglycemia and diminish the risk for late hypoglycemia in some patients with insulin-requiring diabetes mellitus treated with conventional injections of insulin.

Diabetes Mellitus, Type 1↗