Search PubMed⌕ Search

Biomedical subjects

D Drucker

Publications and source records attributed to D Drucker.

At least 19 recordsLinked to original sources
PubMed2001

Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor.

Activation of the hepatoportal glucose sensors by portal glucose infusion leads to increased glucose clearance and induction of hypoglycemia. Here, we investigated whether glucagon-like peptide-1 (GLP-1) could modulate the activity of these sensors. Mice were therefore infused with saline (S-mice) or glucose (P-mice) through the portal vein at a rate of 25 mg/kg. min. In P-mice, glucose clearance increased to 67.5 +/- 3.7 mg/kg. min as compared with 24.1 +/- 1.5 mg/kg. min in S-mice, and glycemia decreased from 5.0 +/- 0.1 to 3.3 +/- 0.1 mmol/l at the end of the 3-h infusion period. Coinfusion of GLP-1 with glucose into the portal vein at a rate of 5 pmol/kg. min (P-GLP-1 mice) did not increase the glucose clearance rate (57.4 +/- 5.0 ml/kg. min) and hypoglycemia (3.8 +/- 0.1 mmol/l) observed in P-mice. In contrast, coinfusion of glucose and the GLP-1 receptor antagonist exendin-(9-39) into the portal vein at a rate of 0.5 pmol/kg. min (P-Ex mice) reduced glucose clearance to 36.1 +/- 2.6 ml/kg. min and transiently increased glycemia to 9.2 +/- 0.3 mmol/l at 60 min of infusion before it returned to the fasting level (5.6 +/- 0.3 mmol/l) at 3 h. When glucose and exendin-(9-39) were infused through the portal and femoral veins, respectively, glucose clearance increased to 70.0 +/- 4.6 ml/kg. min and glycemia decreased to 3.1 +/- 0.1 mmol/l, indicating that exendin-(9-39) has an effect only when infused into the portal vein. Finally, portal vein infusion of glucose in GLP-1 receptor(-/-) mice failed to increase the glucose clearance rate (26.7 +/- 2.9 ml/kg. min). Glycemia increased to 8.5 +/- 0.5 mmol/l at 60 min and remained elevated until the end of the glucose infusion (8.2 +/- 0.4 mmol/l). Together, our data show that the GLP-1 receptor is part of the hepatoportal glucose sensor and that basal fasting levels of GLP-1 sufficiently activate the receptor to confer maximum glucose competence to the sensor. These data demonstrate an important extrapancreatic effect of GLP-1 in the control of glucose homeostasis.

Animals↗
PubMed1998

Transesophageal echocardiographic diagnosis of a mycotic ascending aortic pseudoaneurysm as a source of embolism.

Pseudoaneurysm of the ascending aorta may develop after aortic injury from trauma or surgery. We report a case of dehiscence of an aortic graft leading to ascending aortic pseudoaneurysm that was diagnosed by transesophageal echocardiography. In addition, the transesophageal echocardiogram identified the pseudoaneurysm as the likely cause of a saddle embolus to the iliac bifurcation of the aorta. This case is also unique in that the patient's pseudoaneurysm was infected with fungus.

Adult↗
PubMed1998

Exendin-(9-39) is an inverse agonist of the murine glucagon-like peptide-1 receptor: implications for basal intracellular cyclic adenosine 3',5'-monophosphate levels and beta-cell glucose competence.

The effect of exendin-(9-39), a described antagonist of the glucagon-like peptide-1 (GLP-1) receptor, was evaluated on the formation of cAMP- and glucose-stimulated insulin secretion (GSIS) by the conditionally immortalized murine betaTC-Tet cells. These cells have a basal intracellular cAMP level that can be increased by GLP-1 with an EC50 of approximately 1 nM and can be decreased dose dependently by exendin-(9-39). This latter effect was receptor dependent, as a beta-cell line not expressing the GLP-1 receptor was not affected by exendin-(9-39). It was also not due to the endogenous production of GLP-1, because this effect was observed in the absence of detectable preproglucagon messenger RNA levels and radioimmunoassayable GLP-1. Importantly, GSIS was shown to be sensitive to this basal level of cAMP, as perifusion of betaTC-Tet cells in the presence of exendin-(9-39) strongly reduced insulin secretion. This reduction of GSIS, however, was observed only with growth-arrested, not proliferating, betaTC-Tet cells; it was also seen with nontransformed mouse beta-cells perifused in similar conditions. These data therefore demonstrated that 1) exendin-(9-39) is an inverse agonist of the murine GLP-1 receptor; 2) the decreased basal cAMP levels induced by this peptide inhibit the secretory response of betaTC-Tet cells and mouse pancreatic islets to glucose; 3) as this effect was observed only with growth-arrested cells, this indicates that the mechanism by which cAMP leads to potentiation of insulin secretion is different in proliferating and growth-arrested cells; and 4) the presence of the GLP-1 receptor, even in the absence of bound peptide, is important for maintaining elevated intracellular cAMP levels and, therefore, the glucose competence of the beta-cells.

Animals↗
PubMed1998

Nationwide telecare for diabetics: a pilot implementation of the HOLON architecture.

This paper presents results from a demonstration project of nationwide exchange of health data for the home care of diabetic patients. A consortium of industry, academic, and health care partners has developed reusable middleware components integrated using the HOLON architecture. Engineering approaches for multi-organization systems development, lessons learned in developing layered object-oriented systems, security and confidentiality considerations, and functionality for nationwide telemedicine applications are discussed.

Computer Communication Networks↗
PubMed1995

Bladder pheochromocytoma in pregnancy without hypertension. A case report.

A 33-year-old nullipara presented at 20 weeks' gestation with episodes of nonsustained ventricular tachycardia, which were controlled with amiodarone. No hypertension was recorded except once after an attack of ventricular tachycardia. Pheochromocytoma was suspected when repeat 24-hour urine catecholamine levels were markedly elevated. Neither computed tomography nor postpartum metaiodobenzylguanidine scan could locate the tumor. Finally it was identified in the bladder by ultrasound after selective venous sampling localized it to the pelvis. It was excised four months postpartum.

Adult↗
PubMed1994

Osteolysis around uncemented acetabular components of cobalt-chrome surface replacement hip arthroplasty.

Ten cases of major osteolysis were identified in patients with hemispherical cobalt chrome acetabular components of cementless resurfacing total hip prostheses at follow-up examinations ranging from two to five years. All components were porous coated with cobalt chrome spheres and were stabilized initially with screws. Five patients were women and five were men, with ages ranging from 20 to 59 years. The radiolucent cystic lesions with peripheral rims of reactive bone formation appeared one to five years after the operation. They measured from 1.5 to 6 cm in the largest diameter and were most often found adjacent to the screws used to secure the acetabular components to the skeleton. On the radiographs, none of the components appeared to be loose. Three patients had revision surgery. In two of the three cases, the implants were found to be firmly fixed. There was no clinical or bacteriologic evidence of infection. The polyethylene articulating surface showed signs of wear in all three cases and in one of the three it dislocated from the metal shell. Granulation tissue was found in the regions of osteolysis, and the diseased tissue contained numerous macrophages and giant cells. Lymphocytes and plasma cells were rare. Numerous small particles of phagocytosed polyethylene and metal in the cells were noted in two cases, whereas only polyethylene was found in the third.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetabulum↗
PubMed1992

The development of parafoveal and mid-peripheral human retina.

The morphological development of parafoveal retina (1-1.5 mm from the foveal center) and the mid-peripheral (4 mm from the foveal center) human retina has been studied from fetal (F) 26 weeks to adulthood. At both retinal points, all layers and neuronal types are present at F26 weeks. In parafovea at F26 weeks photoreceptors have only a rudimentary inner segment and no outer segments. Short outer segments are present on both rods and cones at F36 weeks. By postnatal (P) 5-8 days the inner retina is relatively mature. Photoreceptors have elongated basal axons which cause the photoreceptor layer to become much thicker than in prenatal retina. At birth cone inner segments are untapered, but rod inner segments have already reached their adult width of 2 microns. Both rod and cone inner and outer segments are 30-50% of adult length. By 13 months both inner and outer retina are mature appearing, with the photoreceptors accounting for half the retinal thickness due to the elongation of the fibers of Henle. Cone outer segments elongate up to P5 years and rod outer segments to P13 years. At mid-peripheral or rod-ring retina outer segments are present on rods at F26 weeks and on cones at F36 weeks. At birth the inner retina is adultlike. The outer plexiform layer becomes thicker up to P45 months due to the elongation of fibers of Henle. At birth both rod and cone mid-peripheral inner segments are slightly longer and outer segments are 50% longer than in parafoveal retina. By P5 years mid-peripheral rod outer segments are slightly longer than in parafoveal retina, and this changes little thereafter. This anatomical study has found that the photoreceptors in peripheral rod-ring retina develop earlier than those in more central retina, and in turn parafoveal photoreceptors develop well in advance of foveal cones. This suggests that human neonates may utilize more peripheral retinal regions for some aspects of visual function before foveal cone vision becomes dominant.

Adolescent↗
PubMed1992

Revision of the acetabular component with an uncemented Harris-Galante porous-coated prosthesis.

One hundred and forty revisions for loosening of the acetabular component were performed in 124 patients, with the use of an uncemented Harris-Galante acetabular prosthesis. A component was considered loose if there was a change in its position or vertical or horizontal migration, or both, of four millimeters or more, as demonstrated on serial radiographs. All patients were followed prospectively for a mean of forty-one months (range, twenty-four to seventy-six months). Bone-grafting was performed at the time of the revision in 127 of the hips. Identifiable failure of fixation of the acetabular component occurred in only two hips (1 per cent), which had both severe acetabular bone loss and pelvic discontinuity. In one of these hips, fixation of the component could not be achieved during the revision, and the component subsequently migrated. No other components migrated. Only one patient had a revision of the index acetabular operation. A continuous radiolucency developed at the bone-mesh interface of five acetabular components, and in one other hip a small portion of the mesh separated. This hip was reoperated on for a problem with the femur, and the socket was found to be rigidly fixed. No other evidence of loosening was identified. All of the bone grafts united, but partial resorption of the graft occurred in thirty-nine hips. Although there were substantial osseous defects that necessitated major bone-grafting, revision with the uncemented Harris-Galante porous-coated acetabular component provided superior fixation compared with that reported in other series in which cemented acetabular components were used for revision. Of the 140 hips, eighty-nine (64 per cent) had a postoperative score of good or excellent, according to the Harris hip-rating system. Twenty-eight (70 per cent) of the forty hips that had revision of the acetabular component alone were rated as good or excellent.

Acetabulum↗
PubMed1986

Adrenocortical dysfunction in acute medical illness.

To further characterize the adrenocortical response to acute illness, we measured basal and adrenocorticotropic hormone (ACTH)-stimulated 11-deoxycortisol, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). Acutely ill patients had higher ACTH-stimulated 11-deoxycortisol and androstenedione, and decreased basal and ACTH-stimulated androstenedione/cortisol and DHEAS/cortisol ratios. Our data suggest that a shift away from androgen synthesis toward the glucocorticoid pathway occurs in acute illness.

Acute Disease↗
PubMed1985

Variable adrenocortical function in acute medical illness.

Acute medical illness may produce dramatic changes in endocrine function. Although cortisol levels rise in acute medical illness, changes in adrenocortical function and reserve have not been well documented in medical ICU patients. We evaluated plasma ACTH and cortisol levels, and cortisol response to intravenous ACTH in 40 acutely ill patients and 20 anxious but nonacutely ill controls. A wide range of plasma cortisol values (212 to 8430 nmol/L) was observed. More severely ill patients did not necessarily have higher plasma cortisol values. Patients who survived hospitalization had lower mean initial and post-ACTH cortisol levels than patients who succumbed. ACTH levels varied widely and correlated poorly with levels of plasma cortisol. There was no evidence of occult adrenocortical insufficiency. We conclude that plasma cortisol elevations are common in acute medical illness.

Acute Disease↗
PubMed1985

Inappropriate TSH secretion with abnormal thyrotroph sensitivity to dopamine.

A 47-year-old male schizophrenic with hyperthyroidism was found to have non-neoplastic inappropriate thyrotropin (TSH) secretion. Anterior pituitary function, CT scan and alpha subunit determinations were normal. TSH rose after TRH (7.8 to 22.5 microU/ml) and propylthiouracil (26.1 microU/ml after 3 months) and decreased with oral T3 (Cytomel 25 micrograms po q.i.d.). Cytomel and glucocorticoid infusion blunted but did not completely suppress the TSH response to TRH. Intravenous dopamine infusion (4 micrograms/kg/min) completely suppressed the prolactin but not the TSH response to TRH. The association of schizophrenia and differential thyrotroph sensitivity to dopamine suggests a possible role for dopamine in the pathogenesis of selected cases of non-neoplastic inappropriate TSH secretion.

Dopamine↗
PubMed1984

Ethionamide-induced goitrous hypothyroidism.

A 42-year-old woman developed goitrous hypothyroidism while receiving ethionamide for treatment of an atypical mycobacterial infection. Five weeks after discontinuation of ethionamide therapy, thyroid function had returned to normal. The goitrogenic effect was studied in vitro by incubating ethionamide in various concentrations (10(-3) to 10(-7) mol/L) with ovine thyroid cells in tissue cultures. Ethionamide inhibited the trapping of technetium and organification of iodine at concentrations seen clinically (10(-5) mol/L). Ethionamide appears to be a potential goitrogen in susceptible persons.

Adult↗
PubMed1983

Posttranslational modification of prothyroid hormone.

Posttranslational processing of thyroglobulin may influence its role as the prothyroid hormone. We have examined the role of glycosylation in the subsequent export and iodination of thyroglobulin. We find that glycosylation is necessary both for the movement of thyroglobulin through the cell and for iodination. During posttranslational processing, thyroglobulin is also phosphorylated and carboxymethylated. The implications of these postsynthetic modifications are discussed.

Ammonium Chloride↗