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Author Heller, S.R. url  openurl
  Title Insulin analogues Type Journal Article
  Year 2002 Publication Curr Med Res Opin Abbreviated Journal  
  Volume 18 Suppl 1 Issue Pages s40-s47  
  Keywords Amino Acid Sequence; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Genetic Engineering; Great Britain; Humans; Hypoglycemic Agents; Insulin; Molecular Sequence Data  
  Abstract The move to intensive insulin therapy following the Diabetes Control and Complications Trial has highlighted the major deficiencies in conventional insulin therapy. Patients are exposed to a high risk of hypoglycaemia due to the delay in absorption of conventional soluble insulin and peaked action of medium acting preparations. Two rapid acting insulin analogues, insulin lispro and aspart have been developed with a reduced tendency to self-association. These demonstrate faster absorption and reach higher concentrations after s.c. injection compared to conventional human insulin and this more physiological action reduces post-prandial glucose to a greater extent. However the benefits in clinical trials have been relatively modest with little or no improvement in HbA1c and minor reductions in hypoglycaemic risk. These rather disappointing results are partly due to the inability of regulatory trials to explore clinical benefit but also because it has taken time to learn how to use these preparations to their best advantage. In patient with tightly controlled diabetes the use of analogues leads to major reductions in severe noctumal hypoglycaemia and this is a robust and important indication. It is still uncertain whether either of the new long-acting insulin analogues, insulin glargine or detemir will have significant clinical benefit but it is possible that the combination of both quick and long-acting analogues will lead to tight glycaemic control without the risk of severe hypoglycaemia.  
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  ISSN 0300-7995 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number refbase @ user @ Heller2002 Serial 2222  
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Author Heller, S.R. url  openurl
  Title Abnormalities of the electrocardiogram during hypoglycaemia: the cause of the dead in bed syndrome? Type Journal Article
  Year 2002 Publication Int J Clin Pract Suppl Abbreviated Journal  
  Volume Issue 129 Pages 27-32  
  Keywords Adult; Arrhythmias, Cardiac; Autonomic Nervous System Diseases; Child; Death, Sudden, Cardiac; Diabetes Mellitus, Type 1; Electrocardiography; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin  
  Abstract We have previously demonstrated that experimental hypoglycaemia in adults with type 1 diabetes causes an abnormal electrocardiogram (ECG), with increases in QT interval and dispersion. These abnormalities in cardiac repolarisation indicate a risk of ventricular tachycardia and sudden death in other conditions, including ischemic heart disease and congenital long QT syndrome. We have hypothesised that they could contribute to the dead in bed syndrome--the recently described sudden unexpected death in young people with type 1 diabetes--which occurs around three times more frequently than in those without diabetes. It is clearly impossible to explore the causes of a rare and fatal complication by direct observation. We have therefore explored the pathophysiology in a series of experimental studies involving non-diabetic subjects and surrogate endpoints. These have demonstrated that abnormal cardiac repolarisation occurs consistently during insulin-induced hypoglycaemia and that either potassium infusion or beta-blockade prevents increased QT dispersion but only partially prevents QT lengthening. The sympathoadrenal discharge induced by hypoglycaemia alters cardiac repolarisation by both direct and indirect (by reducing extracellular potassium) mechanisms. Other factors that might contribute to the clinical risk of cardiac arrhythmias during nocturnal hypoglycaemia include autonomic neuropathy. This is associated with prolonged QT interval in the non-hypoglycaemic state and has been proposed as a cause of sudden death in those affected. We have examined cardiac repolarisation during clamped hypoglycaemia in patients with type 1 diabetes, with and without autonomic neuropathy. Our data demonstrate lengthening of QTc (QT interval corrected for heart rate) during hypoglycaemia in all groups with no significant differences between the groups, suggesting that autonomic dysfunction does not contribute to hypoglycaemia-induced QTc lengthening in type 1 diabetes. Our hypothesis would be strengthened by demonstrating similar changes during clinical hypoglycaemia. We have recently completed studies in prepubescent children and adults that show modest but significant changes in QTc during nocturnal hypoglycaemia in both populations. We have also demonstrated that pre-treatment with beta-blocking agents prevents abnormal cardiac repolarisation during experimental hypoglycaemia. This has identified a possible treatment if we can identify patients at high risk. Further work is necessary to determine whether we can reliably identify patients who could be at special risk during hypoglycaemia and who might benefit from protection with agents such as beta-blockers. Sudden death in young people with diabetes is, thankfully, rare. However its consequences are so devastating that an excess risk of 3 to 4 times the non-diabetic population seems sufficient to warrant further investigation of the mechanisms that may cause it.  
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  ISSN 1368-504x ISBN Medium  
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  Notes Approved no  
  Call Number refbase @ user @ Heller2002 Serial 2223  
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Author Heller, S.; Kurtzhals, P.; Verge, D.; Lindholm, A. url  openurl
  Title Insulin aspart: promising early results borne out in clinical practice Type Journal Article
  Year 2002 Publication Expert Opin Pharmacother Abbreviated Journal  
  Volume 3 Issue 2 Pages 183-195  
  Keywords Adolescent; Blood Glucose; Child; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Evaluation; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin  
  Abstract The novel, rapid-acting insulin analogue insulin aspart (IAsp; Novo Nordisk) has been shown in preclinical studies to be more rapidly absorbed than human insulin (HI) when administered subcutaneously. IAsp reaches higher peak serum concentrations in a shorter time than HI, whilst maintaining a similar receptor binding and safety profile. The physiological pharmacokinetic profile of IAsp compared to that of HI has been demonstrated in both adult and paediatric populations and was accompanied by small but statistically significant reductions in HbA(1c), lower postprandial glucose excursions and a reduced risk of late postprandial and major nocturnal hypoglycaemia. Benefits may be maximised by dose optimisation, using bolus doses that result in effective postprandial glucose reduction, as well as higher and multiple basal insulin doses. The safety profile, including cardiovascular risk, is equivalent to HI.  
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  ISSN 1465-6566 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number refbase @ user @ Heller2002 Serial 2225  
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Author Heller, S. url  openurl
  Title Abortion rights of young women: the Supreme Court attacks the most vulnerable Type Journal Article
  Year 1990 Publication Washburn Law J Abbreviated Journal  
  Volume 30 Issue 1 Pages 15-28  
  Keywords Abortion, Induced; Adolescent; Adult; Civil Rights; Confidentiality; Decision Making; Female; Government Regulation; Humans; Judicial Role; Jurisprudence; Men; Minnesota; Minors; Ohio; Parental Consent; Parental Notification; Parents; Paternalism; Pregnancy; Pregnant Women; Prejudice; Privacy; Social Control, Formal; Social Dominance; Spouses; State Government; Supreme Court Decisions; Third-Party Consent; United States; Women; Women's Rights  
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  Series Volume Series Issue Edition  
  ISSN 0043-0420 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number refbase @ user @ Heller1990 Serial 2228  
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Author Mertus, J.; Heller, S. url  openurl
  Title Norplant meets the new eugenicists: the impermissibility of coerced contraception Type Journal Article
  Year 1992 Publication St Louis Univ Public Law Rev Abbreviated Journal  
  Volume 11 Issue 2 Pages 359-383  
  Keywords California; Child Abuse; Civil Rights; Coercion; Contraception; Eugenics; Female; Freedom; Hormones; Humans; Informed Consent; Judicial Role; Jurisprudence; Legislation as Topic; Levonorgestrel; Mandatory Programs; Medicaid; Minority Groups; Mothers; Motivation; Personal Autonomy; Pharmaceutical Preparations; Poverty; Pregnancy; Pregnant Women; Prejudice; Prenatal Exposure Delayed Effects; Privacy; Punishment; Reproduction; Risk; Risk Assessment; Socioeconomic Factors; State Government; Sterilization, Involuntary; Substance-Related Disorders; United States; Vulnerable Populations; Women; Women's Rights  
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  Series Volume Series Issue Edition  
  ISSN 0898-8404 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number refbase @ user @ Mertus1992 Serial 2227  
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