We reviewed the case records of 141 patients (134 with cancer and seven with acquired immunodeficiency syndrome) who died at Memorial Sloan-Kettering Cancer Center between July 11 and September 19, 1991. Do-not-resuscitate orders had been written on 115 (85.8%) of the patients with cancer and all of the patients with acquired immunodeficiency syndrome. The do-not-resuscitate orders appeared to be valid, in that evidence of informed consent was documented in all but two of the cases. Six additional patients who died had family consent not to resuscitate, although no do-not-resuscitate orders were written. Two other patients died unexpectedly. The remaining 11 patients all received aggressive attempts at resuscitation, which were felt to be medically appropriate in all but two cases. The interval between the do-not-resuscitate order and death was between zero and 60 days, with an average of 8.4 days and a median of 6 days; it exceeded 20 days in 14 cases. We attribute the high degree of compliance with the New York State do-not-resuscitate law observed in this study to an intensive program of consultation and education begun in 1987 by the Ethics Committee of Memorial Sloan-Kettering Cancer Center.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Physicians' aid in dying.

Explore the source record for details and available documents.

Christianity↗

PubMed1990

Do-not-resuscitate orders.

Do-Not-Resuscitate (DNR) orders were audited in October and December 1989 at the teaching hospital of the University of Florida College of Medicine in Gainesville. October audit results were presented at a medical staff meeting in November to determine if education would improve compliance. There were 22 DNR orders in October, 17 (77%) were out of compliance with hospital policy due to failure to obtain written consultation from a second attending. Although not required by hospital policy, there were 11 instances (50%) in which patients (or families) were required to provide written documentation of their wishes (a living will) before the attending would write the order. There were 22 DNR orders in December, eight (36%) were out of compliance due to failure to obtain written consultation from a second attending. There were no instances of attendings' requiring patients (or families) to provide written documentation of their wishes. Education improved compliance with hospital DNR policy, but physicians were still reluctant to obtain consultation from colleagues.

Adult↗

PubMed1989

Effects of insulin and streptozotocin-diabetes on isoproterenol-stimulated cyclic AMP production in myocytes isolated from rat heart.

Isoproterenol (ISO), at concentrations of up to 10(-5) mol/L, caused a dose-dependent stimulation of cyclic AMP (cAMP) production in rat cardiomyocytes. At higher ISO concentrations, relative inhibition was seen. Insulin augmented ISO-stimulated cAMP production and appeared to mitigate the toxic effects of high ISO concentrations. This synergy between insulin and ISO observed in cardiomyocytes was not observed in adipocytes. Streptozotocin (STZ)-diabetes abolished the stimulatory effects of insulin on ISO-induced cAMP production in cardiomyocytes.

Animals↗

PubMed1989

Degradation of insulin and insulin-like growth factors by enzyme purified from human erythrocytes. Comparison of degradation products observed with A14- and B26-[125I]monoiodoinsulin.

An insulin-degrading enzyme has been purified from human erythrocytes. This enzyme degraded 125I-labeled insulin-like growth factor I (IGF-I) more slowly than 125I-IGF-II and degraded IGF-II more slowly than 125I-insulin. The time course of 125I-insulin degradation suggested the presence of intermediates, each of which was itself shown to be a substrate for the enzyme. One of these intermediates appeared to be made up entirely of B-chain residues and had HisB10 as its NH2-terminal. The final major radiolabeled degradation product of A14-[125I]monoiodoinsulin was a peptide with TyrA14 at the A-chain NH2 terminal. This peptide could be reduced with dithiothreitol, suggesting that it contained amino acid residues from both A- and B-chains. It was partially precipitated by trichloroacetic acid and anti-insulin antibody but bound poorly to IM-9 lymphocytes. The final major degradation product of B26-[125I]monoiodoinsulin was a peptide whose NH2-terminal was TyrB26 and could not be reduced by dithiothreitol. It was partially precipitated by anti-insulin antibody but was precipitated poorly, if at all, by trichloroacetic acid and bound poorly to IM-9 lymphocytes. The results show that this enzyme degraded insulin by sequential cleavage of peptide bonds on both A- and B-chains. We identified LeuA13-TyrA14, SerB9-HisB10, and PheB25-TyrB26 as three of the bonds that are cleaved.

Chromatography, Gel↗

PubMed1988

Inhibition of insulin-stimulated glucose transport by factor extracted from serum of insulin-resistant patient.

We report a 31-yr-old nondiabetic male patient with acanthosis nigricans whose hyperinsulinemia and insulin resistance could not be explained by anti-receptor antibodies or by an intrinsic defect of insulin binding to his cells. An acid-alcohol extract of the patient's serum contained a factor that inhibited insulin-stimulated glucose transport in rat adipocytes. Low levels of the factor could be detected in 9 of 13 unselected patients with non-insulin-dependent diabetes. The factor was heat stable and resistant to treatment with acid, base, and various lytic enzymes. It eluted from a Bio-Gel P-2 column with an apparent molecular weight of 300. The factor also inhibited stimulation of glucose transport in adipocytes by the insulin mimickers hydrogen peroxide and sodium vanadate. In vitro incubation of rat soleus muscles in the presence of the factor resulted in inhibition of insulin-stimulated glucose transport. The factor enhanced 125I-labeled insulin binding in both adipocytes and muscle. A preparation of insulin receptors obtained from muscles incubated with serum factor showed increased binding of 125I-insulin to the alpha-subunit of the insulin receptor. Autophosphorylation of the beta-subunit and phosphorylation of exogenous substrate were increased in the receptor preparation obtained from muscles that had been incubated with serum factor. However, the increase in kinase activity was approximately the same as the increase in binding activity. No difference in kinase activity was observed when assayed under conditions in which 125I-insulin binding activity had been equalized.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗

PubMed1987

Elevated levels of plasma prorenin (inactive renin) in diabetic and nondiabetic patients with autonomic dysfunction.

We measured plasma inactive renin (prorenin) levels in 46 diabetic patients, 4 nondiabetic patients with idiopathic autonomic dysfunction, and 115 normal subjects. Plasma inactive renin levels were normal in the diabetic patients who had no complications (n = 6) and in those with microvascular disease (n = 8) who did not have coexistent autonomic dysfunction. Plasma inactive renin was either grossly elevated or in the upper limit of the normal range in diabetic patients with autonomic dysfunction (n = 18). No correlation was found between plasma inactive renin and glycemic control, as measured by hemoglobin A1c. High plasma inactive renin levels were also found in the 4 nondiabetic patients with idiopathic autonomic dysfunction. These data suggest that increased plasma inactive renin levels in diabetic patients are a consequence of coexistent autonomic dysfunction. This finding is consistent with other evidence that suggests autonomic regulation of the processing of prorenin to renin within the kidney.

Adult↗

PubMed1986

Iodine retention and thyroid dysfunction in patients on hemodialysis and continuous ambulatory peritoneal dialysis.

Povidone-iodine is frequently used as an antiseptic in patients on chronic dialysis. In order to determine if the use of povidone-iodine affects thyroid function in these patients, we measured serum iodine and thyroid hormone levels in dialysis patients prior to and following discontinuation of topical povidone-iodine antiseptics. Serum inorganic iodine levels were elevated initially in nearly 90% of the patients (19 on hemodialysis, 12 on continuous ambulatory peritoneal dialysis [CAPD]). Following discontinuation of povidone-iodine, iodine levels over a 3-month period decreased modestly in patients on CAPD (n = 5) and were unchanged in patients on hemodialysis (n = 5). Total and free thyroxine levels were frequently low but did not correlate with protein-bound or inorganic iodine levels and did not change after discontinuation of povidone-iodine. Thyrotropin levels correlated significantly (r = .62, P less than .01) with inorganic iodine levels in patients on hemodialysis, but not for patients on CAPD. We conclude that abnormal thyroid function tests are common in dialysis patients but are not related to iodine retention or to the routine use of topical povidone-iodine-containing antiseptics.

Adult↗

PubMed1985

Vasoactive intestinal peptide inhibits insulin-stimulated glucose transport in rat adipocytes.

Patients with tumors secreting vasoactive intestinal peptide (VIP) often develop hyperglycemia and glucose intolerance. Although VIP has been reported to increase glucose output by the liver, the concentration required for this effect greatly exceeds that observed clinically. We therefore investigated the effects of VIP on insulin-stimulated glucose transport in isolated adipocytes. Inhibition of insulin action was observed at a concentration of 1 ng/ml VIP with half-maximal inhibition at approximately 20 ng/ml. 125I-VIP bound to specific high-affinity sites on the adipocytes. Fifty percent inhibition of binding occurred at a concentration of unlabeled VIP of approximately 10 ng/ml and was not affected by insulin, glucagon, or growth hormone. As we have observed previously with glucagon and catecholamines, inhibition of insulin action by VIP was observed only when accumulation of adenosine in the incubation medium was prevented by addition of adenosine deaminase. Under these conditions VIP markedly increased cellular cAMP levels. A good correlation was observed among VIP binding, inhibition of insulin-stimulated glucose transport, and cellular concentrations of cAMP. The results suggest that inhibition of insulin action in adipose tissue contributes to the hyperglycemic effect of VIP. Together, with our published findings on glucagon and catecholamines, these results support the hypothesis that counterregulatory hormones inhibit insulin action by increasing cellular concentrations of cAMP.

Adenosine Deaminase↗