Pharmacodynamic and pharmacokinetic properties of a premixed 85/15 human insulin preparation.

BACKGROUND: Many patients with diabetes use mixtures of fast-acting (regular human) insulin and intermediate-acting (neutral protamine Hagedorn [NPH]) insulin to control their blood glucose levels. Premixed insulin is available in a 70%/30% mixture and a 50%/50% mixture of NPH/regular human insulin. For some patients, however, a premixed formulation containing > or =30% regular human insulin can provide too much fast-acting insulin, potentially causing an increased risk for hypoglycemia in the early hours after injection. OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of a premixed formulation of 85% NPH insulin and 15% regular human insulin (85/15) were compared with those of a premixed 70%/30% NPH/regular human insulin preparation and 100% NPH insulin. METHODS: A 12-hour euglycemic clamp approach was used to assess glucose-lowering effects and serum insulin levels in 36 healthy male volunteers in a single-dose (0.5 U/kg), randomized, double-blind, 3-period, crossover study. RESULTS: From 0 to 8 hours after injection, the glucose-lowering effects and serum insulin levels for the 85/15 premixed insulin preparation were significantly greater than those for NPH insulin (P < or = 0.05) but significantly less than those for the 70/30 premixed insulin preparation. The mean (+/- SEM) maximum glucose infusion rate (GIRmax) was 8+/-0.6 mg/(min x kg) for the 85/15 preparation, 7+/-0.6 mg/(min x kg) for NPH, and 9+/-0.6 mg/(min x kg) for the 70/30 preparation, with time to peak GIR (tmax(GIR)) occurring at 313, 360, and 272 minutes, respectively. Time to peak insulin levels did not differ significantly for the 3 preparations, but maximum serum insulin concentration (Cmax(ins)) was significantly different between the groups (70/30 premix: 54+/-2.2 microU/mL; 85/15 premix: 44+/-2.4 microU/mL; NPH: 35+/-1.7 microU/mL). Glucodynamic effect and serum insulin levels did not differ significantly among preparations during the interval from 8 to 12 hours after injection. Mean serum C-peptide levels ranged from -0.6 to 1.0 ng/mL for each preparation during the 12-hour period after injection. CONCLUSIONS: The 85/15 premixed insulin preparation demonstrated clinical pharmacokinetic and pharmacodynamic properties that were intermediate between, and significantly different from, those of NPH insulin and the 70/30 premixed insulin preparation.

Usefulness of the modified 0-10 Borg scale in assessing the degree of dyspnea in patients with COPD and asthma.

INTRODUCTION: Rapid assessment and monitoring is essential for patients with acute bronchospasm. However, tools for measuring dyspnea or the state of being short of breath are often limited to peak flow, blood gas analysis, and asking patients multiple questions about their breathing at a time when they find speaking difficult. We thus decided to examine a tool called the modified Borg scale (MBS) that had the potential to provide quick, easy, and rapid information about a patient's subjective state of dyspnea. This 0 to 10 rated scale gave our ED patients a device they could use to measure and evaluate their dyspnea. For this reason, we added it to the triage assessment practice and included it in all posttreatment assessment notes on patients with exacerbations of asthma or chronic obstructive pulmonary disease (COPD) who were seen in the emergency department and urgent care clinic. STUDY QUESTIONS: (1) Can patients with acute bronchospastic asthma or COPD adequately communicate their level of dyspnea using the MBS? (2) Does subjective improvement in the patient's dyspnea using the MBS correlate with improvements in pulmonary functions as measured by the peak flow meter and cutaneous oxygen saturation (Sao(2))? METHODS: Routine and triage assessment of subjective dyspnea using the MBS was instituted at a hospital emergency department serving adult veterans. Concurrently, the MBS was added to our standardized treatment protocol for management of patients with bronchospasm. ED and urgent care records were reviewed to collect baseline and postrespiratory treatment data on peak expiratory flow rates (PEFR), MBS scores, and Sao(2) percentages. RESULTS: Four hundred male veterans aged 24 to 87 years presented with a chief complaint of dyspnea. The assessing physician identified 102 of these patients as having acute bronchospasm; 42 were diagnosed with asthma, and 60 were diagnosed with COPD. All study patients with acute bronchospasm were able to use the MBS to rate their perception of severity of dyspnea. As the peak flow measurements increased, the MBS scores of difficulty breathing decreased. For the asthma groups, the mean MBS score decreased from 5.1 at triage baseline to 2.4 after treatment. This finding indicated that a significant correlation existed between the change in MBS scores and the change in PEFR from pretreatment to posttreatment scores (r = -.31, P <.05). As the peak flow increased, the MBS scores decreased. Sao(2) only slightly improved in the asthma group compared with the COPD group. For patients with COPD, the mean MBS score decreased from 6.0 at triage baseline to 3.0 after treatment. This finding indicated that a significant correlation also existed between the change in MBS scores and the change in PEFR from pretreatment to posttreatment scores (r = -.42, P <.001). Cutaneous oxygen saturation also improved in the COPD group after treatment. The modality of treatment ordered by the physician was metered dose inhaler or nebulizer. These treatment modalities had no effect on the aforementioned results in the asthma or COPD group. CONCLUSIONS: The MBS is a valid and reliable assessment tool for dyspnea. This study demonstrated that it correlated well with other clinical parameters and could be useful when assessing and monitoring outcomes in patients with acute bronchospasm. Patients who used the MBS rated it with a high degree of satisfaction on ease of use and found that the language in this scale adequately expressed their dyspnea. The ED triage and primary care nursing staff rated the MBS as highly satisfactory, stating that it was quick and easy to use. Respiratory assessment in the triage notes and nursing notes were streamlined to consistently include 3 respiratory measures: PEFR, MBS, and Sao(2). Long respiratory narratives were found to be unnecessary in many cases. In addition, the MBS helped to include an important element of subjective assessment when evaluating the severity of dyspnea.

Demonstration of 20K growth hormone in human plasma by gel electrophoretic-immunostaining-autoradiographic assay (GEISAA).

A variant of human growth hormone (hGH), in which 15 amino acids are missing (commonly referred to as 20K-hGH in contrast to the traditional form which is referred to as 22K-hGH), is known to exist in human pituitary glands. However, lack of a method to measure it in blood has hindered investigations of its physiopathology. We have applied a newly-developed technique called GEISAA for its detection in small volumes of human plasma. The method is based upon the lower Mr of the variant and its ability to partially crossreact with existing antibodies for 22K-hGH. It consists of retrieval of the substance from plasma by immunoprecipitation, separation from 22K-hGH by NaDodSO4-polyacrylamide gel electrophoresis, transfer onto nitrocellulose paper by electroblotting and visualization by immunostaining and autoradiography. It revealed the 20K-hGH in plasma of some normal individuals and in that of an acromegalic patient. Furthermore, plasma concentration of the variant rose in conjunction with 22K-hGH following exercise, a natural stimulus for GH release. These results show that the 20K-hGH circulates under normal conditions and it is measurable by GEISAA using existing antibodies.