Biomedical subjects

D K Andersen

Publications and source records attributed to D K Andersen.

At least 37 records · Page 2Linked to original sources

PubMed1991

Taking the lead: challenges of supply and demand in academic surgery.

I have tried to forecast some of the real challenges which we will all face within our departments over the next few years. If we are to be successful in attracting the best and the brightest young people to join us in the pursuit of an academic surgical career, we must serve as role models, genuine role models, for what may be a decreasing pool of medical students entering our institutions. Second, we must reward those individuals in our departments who truly inspire and motivate our young trainees, whether this inspiration is at the bedside, in the operating rooms, or in the laboratories. Third, we must begin to explore new initiatives where professional organizations and associations such as the AAS can reach out to these young trainees and help them realize early on the advantages and gratification of a career in academic surgery. Fourth, we must realize that academic and research training, like charity, begins at home. Through workshops, local seminars, and training programs modeled after the one which seems to have been so successfully done by the AAS, our departments and institutions can begin to teach solid research skills and demonstrate a genuine commitment for the future success of our young trainees. Finally, we have to rethink our notion of the model academic surgical department. The time has passed where every surgical faculty member should be at the beck and call of the operating room. If we take our obligations to recruiting and training young academic surgeons seriously, we will realize that it is not enough for use to simply sit back and wait for them to come.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers↗

PubMed1991

Recurrent abdominal pain due to chronic appendiceal disease.

Recurrent appendicitis and chronic appendicitis are the subjects of much controversy, but long-standing inflammation of the appendix and surrounding tissues has been reported in rare instances. We have described two patients, both with recurrent episodes of abdominal pain, who subsequently were shown to have chronic appendiceal disease. Appendiceal disease should be considered in the differential diagnosis in patients with recurrent abdominal pain.

Abdominal Pain↗

PubMed1990

Selective neurohormonal interactions in islet cell secretion in the isolated perfused human pancreas.

To investigate the effects of stimulant interactions on alpha- and beta-cell secretions, the differential effects of gastric inhibitory polypeptide (GIP) and cholinergic stimulation (CS) on insulin (IRI) and glucagon (IRG) release were examined during euglycemic, single-pass perfusion in the isolated human pancreas. Pancreata obtained from 12 cadaver organ donors were perfused for 15-min test periods with (a) 1 nM GIP (b) intrinsic CS via bipolar electrical stimulation (10 V, 5 msec, 10 Hz) of the splanchnic neural fibers during simultaneous perfusion with 4 microM phentolamine and 6 microM propranolol, or (c) GIP and CS. The integrated response of IRI and IRG demonstrated that IRI release was stimulated 308 +/- 52 microU/g-min by GIP, 366 +/- 73 microU/g-min by CS, and 560 +/- 50 microU/g-min by GIP and CS (P less than 0.05). IRG release was stimulated 111 +/- 33 pg/g-min by GIP, 34 +/- 12 pg/g-min by CS, and 90 +/- 36 pg/g-min by GIP and CS. Combined hormonal and cholinergic stimulation was additive for IRI release, but not for IRG release. We conclude that the interaction of neural and hormonal islet cell stimuli is cell-type specific. This may result in selective impairment of hormone release after pancreatic denervation.

Adolescent↗

PubMed1990

The effect of pancreatic polypeptide infusion on glucose tolerance and insulin response in longitudinally studied pancreatitis-induced diabetes.

Glucose intolerance is often associated with pancreatitis. Pancreatitis-induced diabetes represents a different clinical syndrome than type I and type II diabetes mellitus. Patients with pancreatitis-induced diabetes may be extremely sensitive to exogenous insulin, rarely develop ketoacidosis, and rarely exhibit classic diabetic complications, such as retinopathy, nephropathy, or accelerated vasculopathy. Pancreatic polypeptide (PP) deficiency has been implicated in the defect of glucose homeostasis found after pancreatitis. This study evaluated intravenous and oral glucose tolerance and insulin response to glucose loading, in the setting of pancreatitis, with and without short-term PP replacement. Dogs (n = 7) underwent pancreatic duct ligation (PDL) and were studied with and without PP infusion (2 micrograms/kg/hr) before PDL and at 1 week, 6 weeks, and 4 months after PDL by means of intravenous and oral glucose tolerance tests. Basal and bombesin-stimulated PP levels at 4 months after PDL were subnormal, verifying PP deficiency in these animals with pancreatitis. PP levels during PP infusion reproduced normal postcibal levels, averaging 897 +/- 40 pg/ml. Glucose tolerance, expressed as the glucose decay constant for the intravenous glucose tolerance tests and as the integrated glucose response for the oral glucose tolerance tests, deteriorated over time and was not improved by acute PP replacement. The integrated insulin response to glucose was not affected by PP. The acute infusion of PP at a dose that reproduces normal postprandial PP levels fails to improve glucose tolerance or augment insulin release in this model of pancreatitis-induced diabetes.

Administration, Oral↗

PubMed1989

Splanchnic neural regulation of pancreatic polypeptide release in the isolated perfused human pancreas.

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence and absence of selective neural antagonists. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in augmentation of pancreatic polypeptide release. Cholinergic stimulation appears to predominate, whereas beta-adrenergic fibers stimulate pancreatic polypeptide-cell secretion, and alpha-adrenergic fibers inhibit pancreatic polypeptide release. During euglycemia, both cholinergic stimulation and gastric inhibitory polypeptide infusion resulted in a marked release of pancreatic polypeptide. These stimulatory effects were additive, which suggests a linked hormonal and neural mechanism of pancreatic polypeptide release after a meal. In this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role in pancreatic hormone release in man.

Adolescent↗

PubMed1989

In vitro hepatic insulin resistance in chronic pancreatitis in the rat.

To investigate the effect of chronic pancreatitis (CP) on in vitro hepatic sensitivity to insulin, the suppression of glucagon-stimulated hepatic glucose production (HGP) by insulin was examined during isolated liver perfusion (ILP) in CP and sham-operated rats. CP was induced at laparotomy by infusion of 50 microliters 99% oleic acid into the common bile duct during temporary occlusion of the proximal hepatic duct in 250- to 350-g Sprague-Dawley rats. Eight to sixteen weeks later, single-pass ILP was performed on fed animals. Glucagon (100 pg/ml) was infused for 30 min; the final 20 min of perfusion was performed with (a) no insulin, (b) 25 microU/ml insulin, or (c) 100 microU/ml insulin. CP and sham rats demonstrated comparable HGP responses to glucagon during the 0- to 10-min period (5.2 +/- 0.5 vs 5.9 +/- 0.5 mg/g/min, P = NS). CP rats demonstrated an HGP response to glucagon alone more evanescent than that in sham rats (20-30 min of HGP, 6.6 +/- 0.6 vs 9.5 +/- 0.4 mg/g/min, P less than 0.05). Sham rats showed a dose-dependent inhibition of HGP by insulin, however (percentage 20-30 min of HGP/0-10 min of HGP for 0, 25, and 100 microU/ml insulin: 166 +/- 12, 125 +/- 7, and 101 +/- 5%, P less than 0.01), whereas CP rats showed no effect of insulin (130 +/- 6, 123 +/- 7, 134 +/- 7%, P = NS). Pre- and postperfusion liver glycogen contents revealed comparable decreases in liver glycogen in both groups: insulin inhibition of HGP in sham rats was accompanied by higher postperfusion glycogen content. These data demonstrate a loss of insulin-mediated suppression of hepatic glucose production in livers obtained from pancreatitic rats. We conclude that CP is accompanied by a primary hepatic resistance to insulin; this defect may play a role in the etiology of pancreatogenic diabetes.

Animals↗

PubMed1989

Pancreatic structure and glucose tolerance in a longitudinal study of experimental pancreatitis-induced diabetes.

Chronic pancreatitis is associated with glucose intolerance and resultant pancreatogenic diabetes. Using the canine pancreatic duct-ligated model of pancreatitis, we serially evaluated pancreatic histology and electron microscopy, tolerance to intravenous and oral glucose, and insulin response to glucose loading. Pancreatic duct ligation caused microscopic evidence of acute pancreatitis at 1 week, progressing to acinar loss and fibrosis consistent with chronic pancreatitis at time periods up to 6 months. The islets of Langerhans showed degranulation early and appeared to be structurally preserved late. Calculated K values indicated a progressive significant deterioration in intravenous glucose tolerance, falling significantly from 3.46 +/- 0.23 basally to 1.51 +/- 0.17 at 6 months after duct ligation (p less than 0.0001). Oral glucose tolerance deteriorated significantly, with the integrated glucose response rising from 23.7 +/- 1.2 g/dl.minute basally to 32.3 +/- 2.8 g/dl.minute at 6 months after duct ligation (p less than 0.05). Integrated insulin response to both intravenous and oral glucose deteriorated with pancreatitis. Pancreatitis-induced glucose intolerance is a consistent feature of this duct-ligated model. Glucose intolerance stabilizes between 4 and 6 months after duct ligation and is associated with pancreatic acinar fibrosis and pancreatic endocrine structural preservation. While the mechanism of altered glucose tolerance may involve mechanical, neural, humoral, or vascular events, our data clearly support the conclusion that pancreatic ductal stenosis with resultant pancreatic fibrosis and chronic pancreatitis is associated with abnormal islet responsiveness leading to circulating insulin deficiency and glucose intolerance, despite histologic and ultrastructural evidence of intact islets of Langerhans.

Amylases↗

PubMed1989

Current diagnosis and management of Zollinger-Ellison syndrome.

The treatment of patients with Zollinger-Ellison syndrome (ZES) has undergone dramatic evolution during the past decade. Although initially regarded as an incurable tumor, resection of gastrinoma for potential cure has been reported in 30% to 40% of selected patients in recent series. Conversely, although definitive control of acid hypersecretion is achieved by total gastrectomy, histamine (H2)-receptor antagonists and the newly introduced agents omeprazole and somatostatin analogues allow effective medical therapy of gastric acid overproduction. Confirmation of the diagnosis is best achieved with the I.V. secretin stimulation test, and tumor localization techniques are mandatory to identify candidates for operative tumor resection. Intraoperative sonography and careful exploration are required for tumor removal; successful tumor resection is associated with prolonged survival. The majority of patients (60%) are still found to have malignant disease at the time of diagnosis, but 10-year overall survival commonly exceeds 40%. The presence of multiple endocrine neoplasia type I (MEN-I) is seen in 10% to 25% of patients; correction of hypercalcemia alone may have therapeutic benefit in some ZES patients, and while gastrinoma resection is rarely possible, MEN-I patients demonstrate prolonged survival. The choice of medical rather than surgical therapy for acid hypersecretion depends on the suitability of each patient for careful and repeated endoscopic and chemical studies, versus the likelihood of a successful postoperative outcome. Socioeconomic, geographic, and related medical factors in each case may dictate the form of long-term antisecretory therapy. Exploration for possible tumor resection is indicated for virtually all patients who have no documented metastatic disease.

Gastric Acid↗

PubMed1989

Escape of hepatic glucose production during hyperglycemic clamp.

The role of the pattern of insulin secretion on hepatic glucose production (HGP) was evaluated with hyperglycemic and euglycemic clamp studies in six normal young nonobese subjects. In the hyperglycemic studies, glucose levels were raised and maintained at 98 mg/dl above basal for 150 min. Each subject responded with a biphasic pattern of immunoreactive insulin (IRI) release. HGP was completely suppressed by 20 min, coincident with the first-phase insulin release. HGP then rose steadily, surpassing the basal rate by 100 min when IRI had reached the peak levels of the first phase. By 130 min, when IRI had surpassed the peak first-phase levels, HGP began to fall. In the euglycemic studies with a square wave of hyperinsulinemia (approximately 25 microU/ml), HGP was suppressed to approximately 60% of basal and remained at that rate. We next repeated the hyperglycemic studies with somatostatin, glucagon, and insulin infusions. In these studies with a square wave of hyperinsulinemia (approximately 40 microU/ml, the level observed during the first phase IRI of the previous hyperglycemic clamps), HGP was suppressed to approximately 43% of basal rate and remained at that rate. These studies indicate insulin regulation of HGP is not only dependent on insulin level but may be strongly influenced by the pattern, over time, of insulin secretion.

Adult↗

PubMed1989

Reversal of in vitro hepatic insulin resistance in chronic pancreatitis by pancreatic polypeptide in the rat.

In vitro isolated liver perfusion in a rat model of chronic pancreatitis (CP) has been shown to demonstrate hepatic resistance to insulin. The ability of pancreatic polypeptide (PP) to reverse the resistance to insulin on glucagon-stimulated hepatic glucose production was therefore investigated in this model. CP was induced in 250 to 300 gm Sprague-Dawley rats by infusion of 50 microliters of 99% oleic acid into the pancreas via the common bile duct. After 6 to 8 weeks, isolated liver perfusion was performed on livers from both CP rats and sham-operated control animals (n = 12, 14), both with and without PP administration. Glucagon infusion (100 pg/ml for 30 minutes) produced a five- to sixfold increase in hepatic glucose production. The integrated hepatic glucose output (IHGO) response to glucagon alone was comparable in pancreatic and sham-operated animals; during period 1 (0 to 10 minutes) IHGO was 7.1 +/- 0.5 mg/gm-min for sham-operated controls (n = 8) and 7.1 +/- 0.4 mg/gm-min for pancreatitic animals (n = 6) without PP treatment. Animals that received PP (100 ng intraperitoneally 5 hours before liver harvest and perfusion with 4.2 ng/ml from 10 to 30 minutes) demonstrated an IHGO for period 1 for the sham (n = 6) and pancreatitic animals (n = 6) of 5.6 +/- 0.6 and 4.8 +/- 0.8 mg/gm-min, respectively. Insulin infusion (100 microU/ml added to perfusate from 10 to 30 minutes) in CP livers without PP revealed impaired responsiveness to insulin; the ratio of period 3 (20 to 30 minutes)/period 1 IHGO was 110% +/- 5% in CP livers compared with 77% +/- 5% in sham controls (p less than 0.01). In contrast, PP treatment restored hepatic responsiveness to insulin to control levels; the period 3/period 1 IHGO was 75% +/- 13% in CP livers treated with PP, which was indistinguishable from the 67% +/- 9% response seen in sham-operated control animals. These data provide the first in vitro evidence of a primary hepatic glucoregulatory role of PP. Therefore PP deficiency may contribute to altered glucose metabolism through the induction of a reversible hepatic resistance to insulin.

Animals↗

PubMed1989

Effects of cyclosporine on glucose metabolism.

Cyclosporine may have deleterious effects on glucose metabolism. This study was designed to characterize more precisely cyclosporine-induced alterations in glucose homeostasis in a large animal model with hyperglycemic and euglycemic clamp studies in addition to simple bolus glucose (IVGTT) and insulin (IVITT) tolerance tests. In experiment 1, IVGTTs and hyperglycemic clamp studies were performed in eight ewes before and after 4 weeks of cyclosporine treatment. Studies were repeated 4 weeks after cessation of therapy. In experiment 2, IVITTs and euglycemic clamp studies were performed in seven ewes before and after 4 weeks of cyclosporine treatment. Fasting glucose and insulin levels were not affected by cyclosporine treatment. In experiment 1 cyclosporine did not alter IVGTTs; however, during sustained hyperglycemia, cyclosporine caused a 37% decrease in net glucose disposal (p less than 0.001) and a 39% decrease in plateau plasma insulin levels (p less than 0.05). In experiment 2 cyclosporine had no effect on IVITTs. Plateau insulin values in euglycemic clamp studies were lowered by 27% (p less than 0.05) after cyclosporine treatment. In addition, the metabolic clearance rate of insulin was increased by 25% (p less than 0.05), and the steady-state insulin clearance rate was increased by 16% (p less than 0.003). Measurements of insulin sensitivity were unchanged by cyclosporine. These experiments suggest that cyclosporine treatment results in impairment of sustained synthesis and secretion of insulin, increased insulin clearance, and unaltered insulin sensitivity.

Animals↗

PubMed1988

Regulation of pancreatic polypeptide secretion in the isolated perfused human pancreas.

The isolated perfused human pancreas was used as a model to assess factors mediating the pancreatic polypeptide cell response to glucose, insulin, gastric inhibitory polypeptide, and splanchnic nerve stimulation. Pancreases obtained from 18 cadaveric organ donors were isolated and perfused by way of the splenic artery utilizing a Krebs bicarbonate buffer in a single-pass perfusion system. Hormonal stimulation and inhibition of pancreatic polypeptide secretion were assessed, as was the influence of direct electrical stimulation of celiac neural fibers innervating the pancreas. In this in vitro human model, pancreatic polypeptide cell secretion was inhibited by hyperglycemia, although the presence of gastric inhibitory polypeptide augmented the pancreatic polypeptide cell response. Perfusion with low levels of insulin and splanchnic nerve stimulation augmented the response of the pancreatic polypeptide cell to hyperglycemia and gastric inhibitory polypeptide. Since the immunoreactive pancreatic polypeptide response was augmented when insulin and somatostatin release was inhibited by perfusion insulin or nerve stimulation, we conclude that the pancreatic polypeptide cell is regulated by the ambient degree of somatostatin release, insulin release, or both. These findings support a centrifugal pattern of intraislet blood flow.

Adolescent↗

PubMed1988

Reversal of abnormal glucose production after pancreatic resection by pancreatic polypeptide administration in man.

Pancreatic polypeptide (PP) deficiency has been associated with impaired hepatic sensitivity to insulin and pancreatogenic diabetes in chronic pancreatitis. Since pancreatic resection might also result in PP deficiency, hepatic responses to insulin infusion (0.25 mU/kg/min) were determined by the euglycemic glucose clamp technique in 10 patients who had previously undergone pancreatic resection for trauma and in eight healthy control subjects. Six resection patients (RES-PP) demonstrated deficient PP levels, with a mean increase of plasma immunoreactive PP of 20 +/- 7 pg/ml above basal rate after a test meal compared with 232 +/- 82 pg/ml in control subjects (p less than 0.01) and 353 +/- 133 pg/ml in four other patients undergoing resection with normal levels of immunoreactive PP (RES + PP) (p less than 0.03). Three identical insulin infusion studies were performed in each subject, the second of which was performed during the final 2 hours of an 8-hour infusion of bovine PP (2.0 pmol/kg/min). Whereas hepatic glucose production (HGP) in control subjects fell 74% +/- 4% from a basal rate of 2.0 +/- 0.1 mg/kg/min to a 60- to 120-minute value of 0.5 +/- 0.1 mg/kg/min during insulin infusion, HGP was suppressed only 58% +/- 5% in RES-PP subjects, from 1.9 +/- 0.1 to 0.8 +/- 0.1 mg/kg/min (p less than 0.05 vs controls). Intravenous infusion of PP corrected the hepatic resistance to insulin seen in the PP-deficient group. During PP infusion, HGP was suppressed 74% +/- 5% in RES-PP subjects, from 2.1 +/- 0.2 to 0.5 +/- 0.1 mg/kg/min (p less than 0.04 compared with initial study). PP infusion produced no significant change in glucose metabolism in control and RES + PP subjects. Overall glucose disposal rates were not altered by PP infusion in any group. These findings support a role of PP as a glucoregulatory hormone and suggest that PP deficiency may serve as a reversible pathophysiologic factor in the abnormal glucose metabolism seen after pancreatic resection.

Adult↗

PubMed1987

Splanchnic neural regulation of insulin and glucagon secretion in the isolated perfused human pancreas.

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence or absence of selective neural blockers. The insulin and glucagon responses to hyperglycemia alone or in the presence of splanchnic nerve stimulation were similar in magnitude to the results obtained in a preliminary report on isolated human pancreatic function and in studies using animal models. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in an inhibition of insulin release and in an augmentation of glucagon release. alpha-adrenergic stimulation resulted in a strong suppression of insulin secretion and a mild suppression of glucagon secretion. beta-adrenergic fiber stimulation caused a mild augmentation of both insulin and glucagon release, whereas the cholinergic fibers strongly stimulated both alpha- and beta-cell secretion. The predominant effects of celiac neural bundle stimulation are insulin inhibition by was of an alpha-adrenergic effect and glucagon stimulation by way of a cholinergic effect. Thus, in this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role on pancreatic hormone release in human subjects.

Adolescent↗

PubMed1986

Reversal of abnormal glucose metabolism in chronic pancreatitis by administration of pancreatic polypeptide.

Chronic pancreatitis, induced in dogs by pancreatic duct ligation, is associated with glucose intolerance due to insulin deficiency, reduced hepatic sensitivity to insulin, and a marked deficiency of pancreatic polypeptide. Treatment with a 14 day continuous subcutaneous infusion of pancreatic polypeptide resulted in improved oral glucose tolerance and improved hepatic glucose responses to insulin in dogs with chronic pancreatitis. No effect of continuous subcutaneous infusion of pancreatic polypeptide was seen in the control dogs. The time course of the effect of continuous subcutaneous infusion on the hepatic response to insulin was relatively immediate, whereas the effects on improvement in oral glucose tolerance were prolonged. We conclude that pancreatic polypeptide may function physiologically to enhance the hepatic glucose response to insulin and that alterations in glucose metabolism seen in chronic pancreatitis may be due, in part, to a deficiency in pancreatic polypeptide. Since treatment with continuous subcutaneous infusion of pancreatic polypeptide restored the hepatic response to insulin and oral glucose tolerance to more normal levels in our animal model, administration of pancreatic polypeptide may play a therapeutic role in the treatment of certain forms of pancreatogenic diabetes.

Animals↗

PubMed1986

Evaluation of insulin secretion after pancreas autotransplantation by oral or intravenous glucose challenge.

Segmental pancreatic autotransplantation is accompanied by surgical alterations to the pancreas that may have consequences for carbohydrate metabolism. Four mongrel dogs were evaluated before operation and sequentially until 40 weeks after total pancreatectomy and autotransplantation of the splenic lobe of the pancreas with bolus intravenous and oral administration. Intravenous glucose tolerance test (IVGTT) (0.5 g/kg) revealed maintenance of fasting euglycemia for as long as 40 weeks after operation. Peak glucose and integrated glucose values did not show significant changes as a result of autotransplantation. Following transplantation, a delayed peak insulin response was seen; however, basal, peak, and integrated insulin values were largely unaltered. Only K values, a measure of glucose disposal, showed severe alterations (2.44 +/- 0.21 before operation to 1.24 +/- 0.30 at 40 weeks after operation). Oral glucose tolerance tests (OGTT) (2.0 g/kg) demonstrated an increased peak hyperglycemic response after autotransplantation with increased integrated glucose responses. Insulin levels remained at those levels seen before operation, and glucose-dependent insulinotropic polypeptide (GIP) responses were unchanged during the OGTT as late as 20 weeks after operation. In conclusion, pancreas autotransplantation after total pancreatectomy results in significant metabolic alterations that the IVGTT fails to detect with absolute glucose or insulin levels. However, K values are significantly lowered, which indicates alterations in cellular glucose transport. The OGTT demonstrates hyperglycemia without increased insulin or GIP levels, which suggests an altered beta cell response to the enteric stimulus of insulin release. These changes are nonetheless well tolerated by animals that have remained clinically healthy and euglycemic in the basal state.

Animals↗

PubMed1985

The effect of age and glucose concentration on insulin secretion by the isolated perfused rat pancreas.

Age changes in the beta-cell's sensitivity to glucose as well as in its overall capacity to secrete insulin may play a part in the glucose intolerance of aging. The isolated perfused rat pancreas preparation was used to study the effect of age and glucose level on insulin secretion. Overnight-fasted male Wistar 12- and 23-month-old rats had basal plasma glucose levels of 106 +/- 4 (SE) and 100 +/- 4 mg/dl. Perfusate glucose levels were raised from 80 mg/dl to either 150, 220, or 360 mg/dl for 50 min (n = 6 to 8 in each group). Insulin secretion followed the typical biphasic pattern of an early spike and fall, followed by a sustained gradual increase at both ages. First-phase (0-10 min) insulin secretion in the old rats was significantly lower at 150 (184 vs. 524 microU/min, P less than 0.05) and 220 mg/dl (327 vs. 644 microU/min, P less than 0.05), while it was nearly identical at 360 mg/dl. Although lower in the old rats, second-phase (11-50 min) insulin secretion was not statistically significantly different for each glucose level. When first- and second-phase insulin secretion rates were combined, the old rats' insulin secretion was only lower at the 150 mg/dl level (248 vs. 426 microU/min, P less than 0.05). Thus, at the more physiological glucose level, old rats showed a significantly lower response, while at the higher levels insulin secretion was similar. This diminishing age effect with increasing glucose dose suggests a defect in islet sensitivity to glucose rather than a diminished capacity to secrete insulin.

Aging↗

PubMed1985

Current status of adrenalectomy for Cushing's disease.

To evaluate the current use of adrenalectomy in the treatment of Cushing's disease, we reviewed seven consecutive patients who have undergone adrenalectomy for Cushing's disease at this medical center during 1983 to 1984. Seventy-one percent (5/7) had pituitary, or type I, Cushing's disease, while 29% (2/7) had adrenal, or type II, Cushing's disease from either an adenoma or an adrenocortical carcinoma. Presenting signs and symptoms, either initially or at the time of recurrence, were typical of Cushing's syndrome. Four of five patients with type I disease had recurrent disease after transphenoidal hypophysectomy, bilateral adrenalectomy, or unilateral adrenalectomy. In three of five patients, medical therapy of hypercortisolism was abandoned because of adverse side effects. Preoperative evaluation in all patients included cortisol and ACTH levels, dexamethasone suppression tests, and computerized tomography (both abdominal and head). In patients with a prior history of adrenalectomy, radiocholesterol scans were also performed and were useful. Angiographic procedures were not required in these patients. In patients with type I disease, posterior operative approaches were used. In patients with type II disease, an anterolateral approach was used. Posterolateral incisions are preferred over Hugh-Young incisions and provide better exposure with a reduced risk of poor wound healing. Morbidity and mortality included one death and three nonhealing wounds. In the six surviving patients, symptoms resolved with variable frequency. Findings suggestive of Nelson's syndrome (hyperpigmentation) have occurred in two patients; serial computerized tomographic scans fail to reveal evidence of pituitary tumors. We conclude that adrenalectomy remains an essential form of therapy for patients with Cushing's syndrome caused by adrenal tumors or recurrence after previous surgery. The response to the operation is generally good, but long-term surveillance is required for the development of Nelson's syndrome.

19-Iodocholesterol↗