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  • 1
    Electronic Resource
    Electronic Resource
    Effect of 14 days' subcutaneous administration of the human amylin analogue, pramlintide (AC137), on an intravenous insulin challenge and response to a standard liquid meal in patients with IDDM (1996)
    Springer
    Diabetologia 39 (1996), S. 492-499 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; amylin ; pramlintide hyperglycaemia ; glycaemic control ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Individuals with insulin-dependent diabetes mellitus (IDDM or type 1 diabetes) are deficient in both insulin and amylin, peptides secreted by the beta cell. We have investigated the effects of amylin replacement therapy employing the human amylin analogue, pramlintide (25, 28, 29-pro-human amylin, previously referred to as AC137), upon the responses to a standardized insulin infusion (40 mU · kg−1 · h−1) for 100 min and a liquid Sustacal meal (360 kcal) in 84 healthy IDDM patients. Following baseline evaluations, patients were randomly assigned to receive subcutaneous injections of placebo, 30, 100 or 300 Μg pramlintide 30 min before meals for 14 days. There was no meaningful difference between adverse events reported by the 30-Μg pramlintide and the placebo groups, but ten subjects withdrew due to nausea, eight of these in the 300-Μg dose group. Peak plasma pramlintide concentrations for the 30-Μg group were 21±3 and 29±5 pmol/l on Days 1 and 14, respectively. These values are similar to postprandial plasma amylin concentrations in normal volunteers. The plasma glucose, free insulin, glucagon, epinephrine and norepinephrine concentrations during the insulin infusion test before and after therapy were identical in each of the groups. Prior to pramlintide therapy, Sustacal ingestion produced a 4.0–4.8 mmol/l rise in plasma glucose concentrations in each of the groups. Pramlintide therapy reduced postprandial hyperglycaemia as reflected by the 3-h incremental AUCglucose (AUCglucose above or below fasting glucose concentration) Day 1 vs Day 14: 30 Μg, 322±92 vs −38±161 mmol/l · min, p=0.010; 100 Μg, 317±92 vs −39±76 mmol/l · min, p=0.001; and 300 Μg, 268±96 vs −245±189 mmol/l · min, p=0.077. Thus, pramlintide therapy with these regimens did not appear to impair either in vivo insulin action or the counter-regulatory response to hypoglycaemia but did show a clear effect of blunting postprandial hyperglycaemia following a standardized meal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400683
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of 14 days' subcutaneous administration of the human amylin analogue, pramlintide (AC137), on an intravenous insulin challenge and response to a standard liquid meal in patients with IDDM (1996)
    Springer
    Diabetologia 39 (1996), S. 492-499 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; amylin ; pramlintide hyperglycaemia ; glycaemic control ; insulin resistance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Individuals with insulin-dependent diabetes mellitus (IDDM or type 1 diabetes) are deficient in both insulin and amylin, peptides secreted by the beta cell. We have investigated the effects of amylin replacement therapy employing the human amylin analogue, pramlintide (25, 28, 29-pro-human amylin, previously referred to as AC137), upon the responses to a standardized insulin infusion (40 mU · kg–1· h–1) for 100 min and a liquid Sustacal meal (360 kcal) in 84 healthy IDDM patients. Following baseline evaluations, patients were randomly assigned to receive subcutaneous injections of placebo, 30, 100 or 300 μg pramlintide 30 min before meals for 14 days. There was no meaningful difference between adverse events reported by the 30-μg pramlintide and the placebo groups, but ten subjects withdrew due to nausea, eight of these in the 300-μg dose group. Peak plasma pramlintide concentrations for the 30-μg group were 21 ± 3 and 29 ± 5 pmol/l on Days 1 and 14, respectively. These values are similar to postprandial plasma amylin concentrations in normal volunteers. The plasma glucose, free insulin, glucagon, epinephrine and norepinephrine concentrations during the insulin infusion test before and after therapy were identical in each of the groups. Prior to pramlintide therapy, Sustacal ingestion produced a 4.0–4.8 mmol/l rise in plasma glucose concentrations in each of the groups. Pramlintide therapy reduced postprandial hyperglycaemia as reflected by the 3-h incremental AUCglucose (AUCglucose above or below fasting glucose concentration) Day 1 vs Day 14: 30 μg, 322 ± 92 vs –38 ± 161 mmol/l · min, p = 0.010; 100 μg, 317 ± 92 vs –39 ± 76 mmol/l · min, p = 0.001; and 300 μg, 268 ± 96 vs –245 ± 189 mmol/l · min, p = 0.077. Thus, pramlintide therapy with these regimens did not appear to impair either in vivo insulin action or the counter-regulatory response to hypoglycaemia but did show a clear effect of blunting postprandial hyperglycaemia following a standardized meal. [Diabetologia (1996) 39: 492–499]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400683
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study (1997)
    Springer
    Intensive care medicine 23 (1997), S. 282-287 
    Details
    ISSN: 1432-1238
    Keywords: Key words Septic shock ; Catecholamines ; Intramucosal pH ; Lactic acidosis ; Splanchnic circulation ; Tonometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. Design: A prospective, intervention, randomized clinical trial. Setting: Adult medical/surgical intensive care unit in a university hospital. Patients: 30 patients with a cardiac index (CI) 〉 3.5 l · min–1· m–2 and a mean arterial pressure (MAP) ≤ 60 mmHg after volume loading and dopamine 20 μg/kg per min and either oliguria or hyperlactatemia. Interventions: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. Measurements and main results: Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 ± 1.5 to 5.9 ± 1.0 mmol/l; p 〈 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 ± 1.5 to 2.7 ± 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 ± 5.4 to 21 ± 5.8; p 〈 0.01) and did not change in the norepinephrine-dobutamine group (13.8 ± 5 to 14 ± 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 ± 0.11 to 7.16 ± 0.07; p 〈 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2– arterial PCO2) increased (from 10 ± 2.7 to 14 ± 2.7 mmHg; p 〈 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 ± 0.11 to 7.35 ± 0.07) and the PCO2 gap (from 10 ± 3.0 to 4 ± 2.0 mmHg) were normalized within 6 h (p 〈 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. Conclusions: Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050329
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Comparison of systemic and regional effects of dobutamine and dopexamine in norepinephrine-treated septic shock (1999)
    Springer
    Intensive care medicine 25 (1999), S. 942-948 
    Details
    ISSN: 1432-1238
    Keywords: Key words Septic shock ; Catecholamines ; Intramucosal pH ; Dobutamine ; Dopexamine ; Gastric tonometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To compare the effects of dobutamine and dopexamine on systemic hemodynamics, lactate metabolism, renal function and the intramucosal-arterial PCO2 gap in norepinephrine-treated septic shock. Design: A prospective, interventional, randomized clinical trial. Setting: Adult medical/surgical intensive care unit in a university hospital. Patients: After volume resuscitation, 24 patients were treated with norepinephrine alone titrated to obtain a mean arterial pressure of 75 mmHg and a cardiac index greater than 3.5 l/min-1· m-2. Interventions: Patients were randomized to receive an infusion of dobutamine (n = 12) (5 μg/kg per min) or dopexamine (n = 12) (1 μg/kg per min). Measurements and main results: Baseline measurements included: hemodynamic parameters, renal parameters (diuresis, creatinine clearance and urinary sodium excretion), gastric mucosal-arterial PCO2 gap, arterial and mixed venous gases and arterial lactate and pyruvate levels. These measurements were repeated after 1 (H1), 4 (H4) and 24 (H24) h. No difference was found between dobutamine and dopexamine among H0 and H1, H4 and H24 values for hemodynamics. Dobutamine and dopexamine at low doses had no significant effect on mean arterial pressure, heart rate, cardiac index, oxygen delivery, oxygen consumption and pulmonary artery occlusion pressure. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. After 4 and 24 h lactate concentration decreased in the dobutamine group from 2.4 ± 1 mmol/l to 1.7 ± 0.7 mmol/l and 1.5 ± 0.4 mmol/l, respectively, while it increased in the dopexamine group from 2.3 ± 1 mmol/l to 2.7 ± 1 mmol/l after 4 h and returned to baseline values after 24 h (2.2 ± 0.6). After 24 h the lactate/pyruvate ratio decreased in the dobutamine group from 15 ± 5 to 12 ± 3 (p 〈 0.05) while it was unchanged in the dopexamine group (from 16 ± 6 to 17 ± 4). Arterial pH increased in the dobutamine group from 7.35 ± 0.05 to 7.38 ± 0.07 (p 〈 0.05) while it was unchanged in the dopexamine group (from 7.34 ± 0.01 to 7.35 ± 0.10). The PCO2 gap decreased after 1 and 4 h in both the dobutamine and dopexamine groups (p 〈 0.05 with respect to baseline). When looking at individual responses, however, patients from both groups exhibited an increased gastric PCO2 gap. No difference was found between dobutamine and dopexamine for renal parameters. Conclusions: In norepinephrine-treated septic shock, low doses of neither dobutamine nor dopexamine caused significant effects on systemic hemodynamics and renal function and both dobutamine and dopexamine inconsistently improved the PCO2 gap. The present results support the need for individual measurement of the effects of catecholamine on the PCO2 gap.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050986
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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