Birgitte Brock - Academia.edu (original) (raw)
Papers by Birgitte Brock
Basic & Clinical Pharmacology & Toxicology, 2009
Elderly patients are vulnerable to medication errors and adverse drug events due to increased mor... more Elderly patients are vulnerable to medication errors and adverse drug events due to increased morbidity, polypharmacy and inappropriate interactions. The objective of this study was to investigate whether systematic medication review and counselling performed by a clinical pharmacist and clinical pharmacologist would reduce length of in-hospital stay in elderly patients admitted to an acute ward of internal medicine. A randomized, controlled study of 100 patients aged 70 years or older was conducted in an acute ward of internal medicine in Denmark. Intervention arm: a clinical pharmacist conducted systematic medication reviews after an experienced medical physician had prescribed the patients' medication. Information was collected from medical charts, interview with the patients and database registrations of drug purchase. Subsequently, medication histories were conferred with a clinical pharmacologist and advisory notes recommending medication changes were completed. Physicians were not obliged to comply with the recommendations. Control arm: medication was reviewed by usual routine in the ward. Primary end-point was length of in-hospital stay. In addition, readmissions, mortality, contact to primary healthcare and quality of life were measured at 3-month follow-up. In the intervention arm, the mean length of in-hospital stay was 239.9 hr (95% ) and in the control arm: 238.6 hr (95% CI: 137.6-339.6), which was neither a statistical significant nor a clinically relevant difference. Moreover, no differences were observed for any of the secondary end-points. Systematic medication review and medication counselling did not show any effect on in-hospital length of stay in elderly patients when admitted to an acute ward of internal medicine.
Hormone and Metabolic Research, Feb 1, 2006
Investigation of gene expression is a developing area with several methods available. One method ... more Investigation of gene expression is a developing area with several methods available. One method is quantitative PCR. A major pitfall in quantitative PCR is the normalisation procedure of the gene expression. Many experiments include a housekeeping gene, some use RNA concentration, and others use a geometric mean of several internal, stably expressed genes. This study demonstrates that real-time-PCR results differ with varying housekeeping genes and analysis protocols when applied to insulin-secreting INS-1E cells derived from the pancreas and stimulated by DEDTC (diethyldithiocarbamate, a zinc chelator) and GLP-1.
Ugeskrift For Laeger, Feb 1, 2008
Penicillin is the drug of choice for treatment of community-acquired pneumonia (CAP) in Denmark. ... more Penicillin is the drug of choice for treatment of community-acquired pneumonia (CAP) in Denmark. The primary determinant for therapeutic activity of penicillin is ''penicillin time'' (T>MIC), i.e. time with penicillin concentration above minimum inhibitory concentration. Eradication of S. pneumoniae requires T>MIC above 40-50%. The second determinant for therapeutic activity is the ratio between maximum penicillin concentration in serum and MIC (Cmax/MIC). Considering penicillin pharmacokinetics, intravenous penicillin 2 million units four times a day is recommended as empirical treatment of CAP.
Fundamental and Clinical Pharmacology, Apr 1, 2005
Abstract Recent years have seen the development of alternatives to human insulin for the treatmen... more Abstract Recent years have seen the development of alternatives to human insulin for the treatment of diabetes. Both rapid-acting and long-acting analogues are available. Alternative routes of insulin administration are emerging. The present review briefly summarizes the present knowledge on insulin analogues and alternative administration routes.
Diabetes Metabolism, 2002
Like many other hormones insulin is released in a pulsatile manner, which results in oscillatory ... more Like many other hormones insulin is released in a pulsatile manner, which results in oscillatory concentrations in peripheral blood. The oscillatory pattern is believed to improve release control and to enhance the hormonal action. Insulin oscillates with a slow ultradian periodicity (approximately 140 min) and a high-frequency periodicity (approximately 6-10 min). Only the latter will be discussed in this review, which focusses almost exclusively on human data. Probably at least 75% of insulin secretion is released in a very regular pulsatile fashion in healthy people. In contrast, type 2 diabetic subjects exhibit in general irregular oscillations of basal plasma insulin. Furthermore, disturbed pulsatile insulin release is also a common feature in people prone to develop diabetes e.g. first-degree relatives of patients with type 2 diabetes. Tiny glucose oscillations (approximately 0.3mM) are capable of easily governing or entraining insulin oscillations in healthy people. This differs from type 2 diabetic individuals underlining a profound disruption of the beta-cells in type 2 diabetes to sense or respond to physiological glucose excursions. A pivotal question is how approximately 1,000,000 islets each containing from a few to several thousand beta-cells can be coordinated to secrete insulin in a pulsatile manner. Coordination is extremely complex involving the intrapancreatic neural network, the intraislet communication and metabolic oscillations in the individual beta-cell itself, but our understanding is still rather rudimentary. It is important to realize how antidiabetic treatment influences high-frequency insulin pulsatility. Only a few studies have been performed, but very recently it has been demonstrated that acute as well as long-term administration of the sulfonylurea compound gliclazide results in a substantial amplification (approximately 50%) of the pulsatile insulin secretion in type 2 diabetes. The fraction between pulsatile vs nonpulsatile insulin secretion is stable, which may be essential for controlling glucose and lipid homeostasis in type 2 diabetes. The influence of repaglinide, thiazolidinediones and a potential future antidiabetic compound (GLP-1) on pulsatile insulin secretion is also discussed briefly. Evaluation of high-frequency insulin pulsatility may be an important player in future tailoring of antidiabetic drugs and may turn out to be relevant as a predictor of type 2 diabetes in people at high risk for developing the disease.
Diabetes, 2004
Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabet... more Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabetes. We explored the effect of short-term (1 week) treatment with a GLP-1 derivative, liraglutide (NN2211), on 24-h dynamics in glycemia and circulating free fatty acids, islet cell hormone profiles, and gastric emptying during meals using acetaminophen. Furthermore, fasting endogenous glucose release and gluconeogenesis (3-3 Hglucose infusion and 2 H 2 O ingestion, respectively) were determined, and aspects of pancreatic islet cell function were elucidated on the subsequent day using homeostasis model assessment and first-and second-phase insulin response during a hyperglycemic clamp (plasma glucose ϳ16 mmol/l), and, finally, on top of hyperglycemia, an arginine stimulation test was performed. For accomplishing this, 13 patients with type 2 diabetes were examined in a double-blind, placebo-controlled crossover design. Liraglutide (6 g/kg) was administered subcutaneously once daily. Liraglutide significantly reduced the 24-h area under the curve for glucose (P ؍ 0.01) and glucagon (P ؍ 0.04), whereas the area under the curve for circulating free fatty acids was unaltered. Twenty-four-hour insulin secretion rates as assessed by deconvolution of serum C-peptide concentrations were unchanged, indicating a relative increase. Gastric emptying was not influenced at the dose of liraglutide used. Fasting endogenous glucose release was decreased (P ؍ 0.04) as a result of a reduced glycogenolysis (P ؍ 0.01), whereas gluconeogenesis was unaltered. First-phase insulin response and the insulin response to an arginine stimulation test with the presence of hyperglycemia were markedly increased (P < From the
Ugeskrift For Laeger, Mar 19, 2007
Infection and Immunity
A monoclonal antibody was used to characterize a 135-kDa surface-located membrane protein (Lmp1) ... more A monoclonal antibody was used to characterize a 135-kDa surface-located membrane protein (Lmp1) generally present in Mycoplasma hominis strains. The monoclonal antibody, 552, was applied to identify the corresponding gene in an expression library of M. hominis PG21 DNA. The M. hominis PG21 lmp1 gene was sequenced, and its gene product was characterized with the goal of elucidating the structure and function of Lmp1. A total of 7,196 bp in the lmp1 region was sequenced. An open reading frame of 4,032 bp, encoding a protein of 1,344 amino acids with a calculated molecular weight of 147,000, was identified. Analysis of the deduced amino acid sequence predicted a hydrophilic protein with a basic pI (10.0). The N-terminal 24 amino acids were a typical leader sequence. Downstream from the first 726 nucleotides, six similar direct repeats of 471 nucleotides were found. In repeat 7, a single-base substitution, C3A, gave rise to the stop codon of lmp1. Thus, the C-terminal 945 amino acids were encoded by the 471-bp direct repeats. As evidenced by Southern blot analysis, the gene encoding the 135-kDa antigen is part of a multigene family. One of the genes, lmp2, was situated directly downstream from lmp1 where the direct repeats continued.
Journal of Bacteriology
Mycoplasma hominis, an opportunistic pathogenic bacterium of humans, has a small genome of 700 kb... more Mycoplasma hominis, an opportunistic pathogenic bacterium of humans, has a small genome of 700 kb. Despite this, multiple copies of gene sequences with similarities to the structural gene (lmp1) of a 135-kDa surface-located membrane protein (Lmp1) have been identified on the genome of M. hominis PG21 (lmp2, lmp3, and lmp4). The distance between the lmp1-lmp2 region and the lmp3-lmp4 region was more than 110 kb. lmp3-lmp4 of M. hominis PG21 was sequenced and found to contain two putative genes. The gene region of 6.5 kb contained a 5 unique region and a 3 unique region separated by 9 0.5-kb repeats with 51 to 90% similarity to 10 similar repeats found in the lmp1-lmp2 region. The 0.5-kb DNA repeats thus comprised about 1% of the entire genome. In both regions, a base change in one of the repeats gave rise to a stop codon, and thereby lmp2 and lmp4 occurred. By PCR amplification of reverse-transcriptase-generated cDNA it was shown that all four genes were transcribed. By use of Lmp-specific antibodies we showed that both lmp1 and lmp3 were translated into proteins (Lmp1 and Lmp3). Each of the four lmp genes represented by their unique cloned segments was used as a probe to analyze the presence, distribution, and organization of the genes within the genome in 13 M. hominis isolates. The repetitive element was detected at one or two locations on the chromosome for all isolates. The lmp3-specific element was present in all isolates, and lmp1-and lmp2-specific elements were present in all but one isolate. The lmp4-specific element was present in about half the isolates tested. For five M. hominis isolates the chromosomal location of the lmp genes was mapped.
Ugeskrift for laeger
Epidemiological studies have suggested that postprandial hyperglycaemia may be a unique risk fact... more Epidemiological studies have suggested that postprandial hyperglycaemia may be a unique risk factor for development of cardiovascular disease, although the predictive value has been minor or disappeared after compensation for other cardiovascular risk factors. Pathophysiological studies have demonstrated that acute changes in blood glucose may induce changes predisposing for development of microangiopathy in the retina, the kidneys and the nerves. Studies have also shown that postprandial hyperglycaemia may be a risk factor for the development of atherosclerosis. No randomised controlled trials have focused on specific treatment of postprandial hyperglycaemia. Therefore, the importance of postprandial hyperglycaemia for development of diabetic complications and atherosclerosis is unclear.
Ugeskrift for laeger
ABSTRACT
Ugeskrift for laeger
Thiazolidinediones (TZD) have recently been introduced as an oral hypoglycaemic agent. A vast amo... more Thiazolidinediones (TZD) have recently been introduced as an oral hypoglycaemic agent. A vast amount of data indicates that TZD also exhibit beneficial cardiovascular effects. This article reports on the results from the large PROactive study. After 3 years of pioglitazone treatment a reduction in the frequency of death, non-fatal myocardial infarction and cerebral infarction was demonstrated in type 2 diabetic subjects. However, there were side effects in terms of cardial insufficiency and edema. Though this study provides some clear cut answers, it also raises a lot of questions.
Diabetes
OBJECTIVE-Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 rece... more OBJECTIVE-Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested whether these neuroprotective effects could relate to changes of glucose transport and consumption.
Ugeskrift for laeger
Vaginal atrophy is a common problem in women who have previously been treated for breast cancer. ... more Vaginal atrophy is a common problem in women who have previously been treated for breast cancer. Endocrine therapy plays an essential role in the treatment of breast cancer. Systemic hormonal treatment is contraindicated. Topical oestrogens are an effective treatment for vaginal atrophy, but are poorly studied in this group of patients. Physicians are reluctant to recommend it because of the potential increase in the risk of recurrence. The sparse data available suggest that vaginal oestrogen may be used relatively safely by women who are in tamoxifen treatment, but should not be used by women who receive aromatase inhibitor treatment.
Basic & Clinical Pharmacology & Toxicology, 2015
Medication errors (MEs) are preventable and can result in patient harm and increased expenses in ... more Medication errors (MEs) are preventable and can result in patient harm and increased expenses in the health care system in terms of hospitalization, prolonged hospitalizations and even death. We aimed to develop a screening tool to detect acutely admitted patients at low or high risk of MEs comprised by items found by literature search and use of theoretical weighting. Predictive variables used for the development of the risk score were found by literature search. Three retrospective patient populations and one prospective pilot population were used for modelling. The final risk score was evaluated for precision by use of sensitivity, specificity and area under the ROC (Receiver Operating Characteristic) curves. The variables used in the final risk score were reduced renal function, the total number of drugs and the risk of individual drugs to cause harm and drug-drug interactions. We found a risk score in the prospective population with an area under the ROC curve of 0.76. The final risk score was found to be quite robust as it showed an area under the ROC curve of 0.87 in a recent patient population, 0.74 in a population of internal medicine and 0.66 in an orthopaedic population. We developed a simple and robust score, MERIS, with the ability to detect patients and divide them according to low and high risk of MEs in a general population admitted at acute admissions unit. The accuracy of the risk score was at least as good as other models reported using multiple regression analysis. This article is protected by copyright. All rights reserved.
Diabetologie und Stoffwechsel, 2007
Basic & Clinical Pharmacology & Toxicology, 2009
Elderly patients are vulnerable to medication errors and adverse drug events due to increased mor... more Elderly patients are vulnerable to medication errors and adverse drug events due to increased morbidity, polypharmacy and inappropriate interactions. The objective of this study was to investigate whether systematic medication review and counselling performed by a clinical pharmacist and clinical pharmacologist would reduce length of in-hospital stay in elderly patients admitted to an acute ward of internal medicine. A randomized, controlled study of 100 patients aged 70 years or older was conducted in an acute ward of internal medicine in Denmark. Intervention arm: a clinical pharmacist conducted systematic medication reviews after an experienced medical physician had prescribed the patients' medication. Information was collected from medical charts, interview with the patients and database registrations of drug purchase. Subsequently, medication histories were conferred with a clinical pharmacologist and advisory notes recommending medication changes were completed. Physicians were not obliged to comply with the recommendations. Control arm: medication was reviewed by usual routine in the ward. Primary end-point was length of in-hospital stay. In addition, readmissions, mortality, contact to primary healthcare and quality of life were measured at 3-month follow-up. In the intervention arm, the mean length of in-hospital stay was 239.9 hr (95% ) and in the control arm: 238.6 hr (95% CI: 137.6-339.6), which was neither a statistical significant nor a clinically relevant difference. Moreover, no differences were observed for any of the secondary end-points. Systematic medication review and medication counselling did not show any effect on in-hospital length of stay in elderly patients when admitted to an acute ward of internal medicine.
Hormone and Metabolic Research, Feb 1, 2006
Investigation of gene expression is a developing area with several methods available. One method ... more Investigation of gene expression is a developing area with several methods available. One method is quantitative PCR. A major pitfall in quantitative PCR is the normalisation procedure of the gene expression. Many experiments include a housekeeping gene, some use RNA concentration, and others use a geometric mean of several internal, stably expressed genes. This study demonstrates that real-time-PCR results differ with varying housekeeping genes and analysis protocols when applied to insulin-secreting INS-1E cells derived from the pancreas and stimulated by DEDTC (diethyldithiocarbamate, a zinc chelator) and GLP-1.
Ugeskrift For Laeger, Feb 1, 2008
Penicillin is the drug of choice for treatment of community-acquired pneumonia (CAP) in Denmark. ... more Penicillin is the drug of choice for treatment of community-acquired pneumonia (CAP) in Denmark. The primary determinant for therapeutic activity of penicillin is &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;penicillin time&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; (T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;MIC), i.e. time with penicillin concentration above minimum inhibitory concentration. Eradication of S. pneumoniae requires T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;MIC above 40-50%. The second determinant for therapeutic activity is the ratio between maximum penicillin concentration in serum and MIC (Cmax/MIC). Considering penicillin pharmacokinetics, intravenous penicillin 2 million units four times a day is recommended as empirical treatment of CAP.
Fundamental and Clinical Pharmacology, Apr 1, 2005
Abstract Recent years have seen the development of alternatives to human insulin for the treatmen... more Abstract Recent years have seen the development of alternatives to human insulin for the treatment of diabetes. Both rapid-acting and long-acting analogues are available. Alternative routes of insulin administration are emerging. The present review briefly summarizes the present knowledge on insulin analogues and alternative administration routes.
Diabetes Metabolism, 2002
Like many other hormones insulin is released in a pulsatile manner, which results in oscillatory ... more Like many other hormones insulin is released in a pulsatile manner, which results in oscillatory concentrations in peripheral blood. The oscillatory pattern is believed to improve release control and to enhance the hormonal action. Insulin oscillates with a slow ultradian periodicity (approximately 140 min) and a high-frequency periodicity (approximately 6-10 min). Only the latter will be discussed in this review, which focusses almost exclusively on human data. Probably at least 75% of insulin secretion is released in a very regular pulsatile fashion in healthy people. In contrast, type 2 diabetic subjects exhibit in general irregular oscillations of basal plasma insulin. Furthermore, disturbed pulsatile insulin release is also a common feature in people prone to develop diabetes e.g. first-degree relatives of patients with type 2 diabetes. Tiny glucose oscillations (approximately 0.3mM) are capable of easily governing or entraining insulin oscillations in healthy people. This differs from type 2 diabetic individuals underlining a profound disruption of the beta-cells in type 2 diabetes to sense or respond to physiological glucose excursions. A pivotal question is how approximately 1,000,000 islets each containing from a few to several thousand beta-cells can be coordinated to secrete insulin in a pulsatile manner. Coordination is extremely complex involving the intrapancreatic neural network, the intraislet communication and metabolic oscillations in the individual beta-cell itself, but our understanding is still rather rudimentary. It is important to realize how antidiabetic treatment influences high-frequency insulin pulsatility. Only a few studies have been performed, but very recently it has been demonstrated that acute as well as long-term administration of the sulfonylurea compound gliclazide results in a substantial amplification (approximately 50%) of the pulsatile insulin secretion in type 2 diabetes. The fraction between pulsatile vs nonpulsatile insulin secretion is stable, which may be essential for controlling glucose and lipid homeostasis in type 2 diabetes. The influence of repaglinide, thiazolidinediones and a potential future antidiabetic compound (GLP-1) on pulsatile insulin secretion is also discussed briefly. Evaluation of high-frequency insulin pulsatility may be an important player in future tailoring of antidiabetic drugs and may turn out to be relevant as a predictor of type 2 diabetes in people at high risk for developing the disease.
Diabetes, 2004
Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabet... more Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabetes. We explored the effect of short-term (1 week) treatment with a GLP-1 derivative, liraglutide (NN2211), on 24-h dynamics in glycemia and circulating free fatty acids, islet cell hormone profiles, and gastric emptying during meals using acetaminophen. Furthermore, fasting endogenous glucose release and gluconeogenesis (3-3 Hglucose infusion and 2 H 2 O ingestion, respectively) were determined, and aspects of pancreatic islet cell function were elucidated on the subsequent day using homeostasis model assessment and first-and second-phase insulin response during a hyperglycemic clamp (plasma glucose ϳ16 mmol/l), and, finally, on top of hyperglycemia, an arginine stimulation test was performed. For accomplishing this, 13 patients with type 2 diabetes were examined in a double-blind, placebo-controlled crossover design. Liraglutide (6 g/kg) was administered subcutaneously once daily. Liraglutide significantly reduced the 24-h area under the curve for glucose (P ؍ 0.01) and glucagon (P ؍ 0.04), whereas the area under the curve for circulating free fatty acids was unaltered. Twenty-four-hour insulin secretion rates as assessed by deconvolution of serum C-peptide concentrations were unchanged, indicating a relative increase. Gastric emptying was not influenced at the dose of liraglutide used. Fasting endogenous glucose release was decreased (P ؍ 0.04) as a result of a reduced glycogenolysis (P ؍ 0.01), whereas gluconeogenesis was unaltered. First-phase insulin response and the insulin response to an arginine stimulation test with the presence of hyperglycemia were markedly increased (P < From the
Ugeskrift For Laeger, Mar 19, 2007
Infection and Immunity
A monoclonal antibody was used to characterize a 135-kDa surface-located membrane protein (Lmp1) ... more A monoclonal antibody was used to characterize a 135-kDa surface-located membrane protein (Lmp1) generally present in Mycoplasma hominis strains. The monoclonal antibody, 552, was applied to identify the corresponding gene in an expression library of M. hominis PG21 DNA. The M. hominis PG21 lmp1 gene was sequenced, and its gene product was characterized with the goal of elucidating the structure and function of Lmp1. A total of 7,196 bp in the lmp1 region was sequenced. An open reading frame of 4,032 bp, encoding a protein of 1,344 amino acids with a calculated molecular weight of 147,000, was identified. Analysis of the deduced amino acid sequence predicted a hydrophilic protein with a basic pI (10.0). The N-terminal 24 amino acids were a typical leader sequence. Downstream from the first 726 nucleotides, six similar direct repeats of 471 nucleotides were found. In repeat 7, a single-base substitution, C3A, gave rise to the stop codon of lmp1. Thus, the C-terminal 945 amino acids were encoded by the 471-bp direct repeats. As evidenced by Southern blot analysis, the gene encoding the 135-kDa antigen is part of a multigene family. One of the genes, lmp2, was situated directly downstream from lmp1 where the direct repeats continued.
Journal of Bacteriology
Mycoplasma hominis, an opportunistic pathogenic bacterium of humans, has a small genome of 700 kb... more Mycoplasma hominis, an opportunistic pathogenic bacterium of humans, has a small genome of 700 kb. Despite this, multiple copies of gene sequences with similarities to the structural gene (lmp1) of a 135-kDa surface-located membrane protein (Lmp1) have been identified on the genome of M. hominis PG21 (lmp2, lmp3, and lmp4). The distance between the lmp1-lmp2 region and the lmp3-lmp4 region was more than 110 kb. lmp3-lmp4 of M. hominis PG21 was sequenced and found to contain two putative genes. The gene region of 6.5 kb contained a 5 unique region and a 3 unique region separated by 9 0.5-kb repeats with 51 to 90% similarity to 10 similar repeats found in the lmp1-lmp2 region. The 0.5-kb DNA repeats thus comprised about 1% of the entire genome. In both regions, a base change in one of the repeats gave rise to a stop codon, and thereby lmp2 and lmp4 occurred. By PCR amplification of reverse-transcriptase-generated cDNA it was shown that all four genes were transcribed. By use of Lmp-specific antibodies we showed that both lmp1 and lmp3 were translated into proteins (Lmp1 and Lmp3). Each of the four lmp genes represented by their unique cloned segments was used as a probe to analyze the presence, distribution, and organization of the genes within the genome in 13 M. hominis isolates. The repetitive element was detected at one or two locations on the chromosome for all isolates. The lmp3-specific element was present in all isolates, and lmp1-and lmp2-specific elements were present in all but one isolate. The lmp4-specific element was present in about half the isolates tested. For five M. hominis isolates the chromosomal location of the lmp genes was mapped.
Ugeskrift for laeger
Epidemiological studies have suggested that postprandial hyperglycaemia may be a unique risk fact... more Epidemiological studies have suggested that postprandial hyperglycaemia may be a unique risk factor for development of cardiovascular disease, although the predictive value has been minor or disappeared after compensation for other cardiovascular risk factors. Pathophysiological studies have demonstrated that acute changes in blood glucose may induce changes predisposing for development of microangiopathy in the retina, the kidneys and the nerves. Studies have also shown that postprandial hyperglycaemia may be a risk factor for the development of atherosclerosis. No randomised controlled trials have focused on specific treatment of postprandial hyperglycaemia. Therefore, the importance of postprandial hyperglycaemia for development of diabetic complications and atherosclerosis is unclear.
Ugeskrift for laeger
ABSTRACT
Ugeskrift for laeger
Thiazolidinediones (TZD) have recently been introduced as an oral hypoglycaemic agent. A vast amo... more Thiazolidinediones (TZD) have recently been introduced as an oral hypoglycaemic agent. A vast amount of data indicates that TZD also exhibit beneficial cardiovascular effects. This article reports on the results from the large PROactive study. After 3 years of pioglitazone treatment a reduction in the frequency of death, non-fatal myocardial infarction and cerebral infarction was demonstrated in type 2 diabetic subjects. However, there were side effects in terms of cardial insufficiency and edema. Though this study provides some clear cut answers, it also raises a lot of questions.
Diabetes
OBJECTIVE-Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 rece... more OBJECTIVE-Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested whether these neuroprotective effects could relate to changes of glucose transport and consumption.
Ugeskrift for laeger
Vaginal atrophy is a common problem in women who have previously been treated for breast cancer. ... more Vaginal atrophy is a common problem in women who have previously been treated for breast cancer. Endocrine therapy plays an essential role in the treatment of breast cancer. Systemic hormonal treatment is contraindicated. Topical oestrogens are an effective treatment for vaginal atrophy, but are poorly studied in this group of patients. Physicians are reluctant to recommend it because of the potential increase in the risk of recurrence. The sparse data available suggest that vaginal oestrogen may be used relatively safely by women who are in tamoxifen treatment, but should not be used by women who receive aromatase inhibitor treatment.
Basic & Clinical Pharmacology & Toxicology, 2015
Medication errors (MEs) are preventable and can result in patient harm and increased expenses in ... more Medication errors (MEs) are preventable and can result in patient harm and increased expenses in the health care system in terms of hospitalization, prolonged hospitalizations and even death. We aimed to develop a screening tool to detect acutely admitted patients at low or high risk of MEs comprised by items found by literature search and use of theoretical weighting. Predictive variables used for the development of the risk score were found by literature search. Three retrospective patient populations and one prospective pilot population were used for modelling. The final risk score was evaluated for precision by use of sensitivity, specificity and area under the ROC (Receiver Operating Characteristic) curves. The variables used in the final risk score were reduced renal function, the total number of drugs and the risk of individual drugs to cause harm and drug-drug interactions. We found a risk score in the prospective population with an area under the ROC curve of 0.76. The final risk score was found to be quite robust as it showed an area under the ROC curve of 0.87 in a recent patient population, 0.74 in a population of internal medicine and 0.66 in an orthopaedic population. We developed a simple and robust score, MERIS, with the ability to detect patients and divide them according to low and high risk of MEs in a general population admitted at acute admissions unit. The accuracy of the risk score was at least as good as other models reported using multiple regression analysis. This article is protected by copyright. All rights reserved.
Diabetologie und Stoffwechsel, 2007