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Biomedical subjects

J Larsen

Publications and source records attributed to J Larsen.

At least 19 recordsLinked to original sources

Heterotrophic bacteria growing in association with Methylococcus capsulatus (Bath) in a single cell protein production process.

The methanotrophic bacterium Methylococcus capsulatus (Bath) grows on pure methane. However, in a single cell protein production process using natural gas as methane source, a bacterial consortium is necessary to support growth over longer periods in continuous cultures. In different bioreactors of Norferm Danmark A/S, three bacteria consistently invaded M. capsulatus cultures growing under semi-sterile conditions in continuous culture. These bacteria have now been identified as a not yet described member of the Aneurinibacillus group, a Brevibacillus agri strain, and an acetate-oxidiser of the genus Ralstonia. The physiological roles of these bacteria in the bioreactor culture growing on natural, non-pure methane gas are discussed. The heterotrophic bacteria do not have the genetic capability to produce either the haemolytic enterotoxin complex HBL or non-haemolytic enterotoxin.

Bacillus↗

Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes.

OBJECTIVE: To evaluate whether simultaneous initial treatment of both insulin resistance and impaired beta-cell insulin secretion with glyburide/metformin tablets is superior to monotherapy with each component agent. RESEARCH DESIGN AND METHODS: In this randomized, parallel-group, placebo-controlled, multicentre study, 806 patients with type 2 diabetes (mean duration, 3 years) who had failed diet and exercise were randomly assigned to 4 weeks of therapy with placebo, glyburide 2.5 mg, metformin 500 mg, glyburide/metformin 1.25/250 mg, or glyburide/metformin 2.5/500 mg once daily. Doses were then titrated over 8 weeks based on glycaemic response. The primary outcome measure was change from baseline in mean HbA1c after 20 weeks. Changes in fasting plasma glucose, lipids and body weight were also assessed along with 2-h postprandial glucose and insulin values after a standardized meal. RESULTS: At week 20, patients taking glyburide/metformin 1.25/250 mg or 2.5/500 mg tablets had greater reductions in HbA1c levels (-1.48% and -1.53% respectively) compared with placebo (-0.21%; both p < 0.001), glyburide (-1.24%; p = 0.016 and p = 0.004 respectively) or metformin (-1.03%; both p < 0.001). Fasting plasma glucose concentrations were reduced more in both glyburide/metformin groups compared with placebo and metformin (p < 0.001); patients in both combination therapy groups also had significantly lower postprandial glucose concentrations compared with placebo, glyburide and metformin. CONCLUSIONS: Initial combination treatment with glyburide/metformin tablets produces greater improvements in glycaemic control than either glyburide or metformin monotherapy. The superiority of initial therapy with glyburide/metformin tablets may arise from simultaneous treatment of both pathophysiological defects of type 2 diabetes.

Blood Glucose↗

Reactive oxygen species generation by leukocytes in populations at risk for atherosclerotic disease.

The aim of this study was to investigate intracellular levels of reactive oxygen species (ROS) in circulating leukocytes in populations at risk for atherosclerosis compared with in healthy individuals. The study populations consisted of 27 non-diabetic men (aged 40-69 years) with untreated hypercholesterolemia (HC), 13 individuals (aged 39-56 years) with well-controlled insulin-dependent diabetes mellitus (DM), and 20 healthy individuals (aged 26-61 years) (REF). Citrated whole blood was collected in fasting condition. Using flow cytometric techniques, the resting levels and the response upon phorbol 12-myristate 13-acetate (PMA, 100 ng/mL) stimulation of ROS were measured in circulating monocytes (MO) and granulocytes (GR). The relative mean fluorescence intensity (rMFI) in 10(4) leukocytes of fluorochromes mainly reflecting the levels of peroxynitrite (ONOO-) hydrogen peroxide (H2O2) and superoxide anion (O2-) was recorded. Significantly, higher basal levels of ONOO- in GR from the combined risk population compared with REF were found (1.4 vs. 1.5 rMFI, p<0.05). Upon PMA stimulation, significantly lower levels of O2 in GR in the risk populations compared to REF (119 vs. 90 Si, p<0.001) were observed. In conclusion, increased resting levels of ROS in circulating granulocytes, but reduced response to PMA stimulation could be demonstrated in populations at risk for atherosclerosis compared with in healthy individuals. This might indicate a higher degree of resting oxidative reactions, with partly exhausted cells and less capacity to host defence.

Adult↗

Primary amyloid tumour of the breast: a case report.

A case of primary amyloid tumour of the breast is reported with a brief review of the literature. The tumour was mammographically suspicious of carcinoma. Fine needle aspiration cytology yielded clumps of amorphous material surrounded by giant cells and lymphocytes. Subsequent histology showed nodular amyloid associated with osseous metaplasia and giant cell reaction. There are 13 cases of amyloid tumour of the breast reported in the literature and in four of these fine needle aspiration had been undertaken.

Aged↗

Identification of putative genes in bean (Phaseolus vulgaris) genomic (Bng) RFLP clones and their conversion to STSs.

A set of 79 previously mapped bean (Phaseolus vulgaris) genomic (Bng) clones were partially sequenced. BLAST database searches detected homologies between 59 of these clones and genes from a variety of plants, especially Arabidopsis thaliana. Some matches in the database to the Bng clones included a putative P-glycoprotein-ABC transporter from Arabidopsis, an early nodulin-binding protein (ENBPI) from Medicago truncatula, a lon-protease protein from spinach, a branched-chain amino-acid aminotransferase from Arabidopsis, and a vacuolar sorting receptor (BP-80) from Pisum sativum. Additional matches were found for genes involved in isoprenoid biosynthesis, sulfur metabolism, proline biosynthesis, and floral development. Sequence tagged site (STSs) were produced for 16 of the clones, 2 of which contain simple sequence repeats (SSRs). Polymorphisms were detected for six of the STSs.

Base Sequence↗

Optimization of DOP-PCR amplification of DNA for high-resolution comparative genomic hybridization analysis.

BACKGROUND: Whole-genome amplification of minute samples of DNA for the use in comparative genomic hybridization (CGH) analysis has found widespread use, but the method has not been well validated. METHODS: Four protocols for degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) and fluorescence labeling were applied to test DNA from normal and K-562 cells. The DNA products were used for CGH analysis. RESULTS: The DOP-PCR-amplified DNA from each protocol produced hybridizations with different qualities. These could be seen primarily as differences in background staining and signal-to-noise ratios, but also as characteristic deviations of normal/normal hybridizations. One DOP-PCR-protocol was further investigated. We observed concordance between CGH results using unamplified and DOP-PCR-amplified DNA. An example of an analysis of an invasive carcinoma of the breast supports the practical value of this approach. CONCLUSIONS: DOP-PCR-amplified DNA is applicable for high- resolution CGH, the results being similar to those of CGH using unamplified DNA.

Breast Neoplasms↗

[Tramadol and oxazepam. Effect on pulmonry function in elderly patients with chronic obstructive lung disease].

Many patients with chronic obstructive pulmonary disease (COPD) suffer from osteoporotic pain as a result of glucocorticoid treatment and nervous symptoms partly related to their lung disease. There seems to be som reluctance to treat these patients with an opioid or benzodiazepine. Upon request, the Drug Information Centre in Odense made an extensive literature search on the subject. No documentation was found that tramadol additionally depresses the respiration in patients with COPD, nor has oxazepam in clinically relevant doses been found to exacerbate their lung disease. The clinical effect is subject to large interindividual variability, and the use of these drugs should, to a greater extent, rest on experience with the individual patient. There seems to be no reason to maintain a priori this rigoristic reluctance to use tramadol and/or oxazepam in patients with COPD.

Aged↗

Changes in the utilisation of lipid-lowering drugs over a 6-year period (1993-1998) in a Danish population.

OBJECTIVE: The effect of lipid-lowering drugs (LLDs) on coronary heart disease is well established. However, their utilisation is often suspected to be too low. The aim of this study was to describe the epidemiology of LLD use with special emphasis on the development of utilisation over a 6-year period in a Danish population. METHODS: For all people who purchased LLDs from 1993 to 1998 in Funen County, all prescriptions for LLDs and co-medication with cardiovascular and antidiabetic drugs were retrieved from Odense University Pharmacoepidemiologic Database (OPED). RESULTS: During the study period, LLD use increased nearly exponentially. In 1998, statins accounted for 95% of the total LLD consumption. The incidence increased markedly around the time of the publication of the Scandinavian Simvastatin Survival Study (4S). Only 3% of the statins were purchased without reimbursement. The female/male ratio was 0.69 and the median age was 60 years. General practitioners issued 73% of the total number of LLD prescriptions, and 55% of the treatments were initiated in general practice. A larger fraction of females and elderly started treatment in general practice. About 40% of the treatments were hospital initiated, and about one-third were followed up in general practice within the first year. CONCLUSIONS: Over the 6 years studied, utilisation of LLDs approached a level that may correspond to the current guideline recommendations. Compliance with guidelines should, however, be studied by following people with coronary heart disease.

Aged↗

Health-related quality of life, symptom distress and sense of coherence in adult survivors of allogeneic stem-cell transplantation.

This is the first Swedish study to evaluate the health-related quality of life and sense of coherence in adult survivors of allogeneic, haematopoietic stem cell transplantation (HSCT). Twenty-five recipients completed three questionnaires 2-4 years after the transplantation. The questionnaires used were the Sickness Impact Profile (SIP), the Symptom Frequency Intensity and Distress (SFID-BMT) scale and the Sense of Coherence (SOC) scale measuring subjective functional status, symptom distress and coping ability. Impairments in functional status were found, as compared with a population norm. The most common impairments were found in the areas of social interaction and sleep and rest. Eye problems, dry mouth, cough, sexual problems, tiredness, anxiety and changes of taste were symptoms reported by more than half of the patients. Despite impaired functioning and a high incidence of symptoms, the general health was described as quite good or excellent by 80% (n = 20) of the patients. The majority (20/22) had also been able to return to work or to attend school. No difference in the sense of coherence was seen, as compared with the population norm. Functional impairments were significantly correlated to a lower degree of sense of coherence.

Adult↗

Guidelines accompanied by changes in reimbursement rules. Effects on lipid-lowering drug prescribing.

OBJECTIVE: To analyse the effect of guidelines accompanied by changes in reimbursement rules for the prescription of lipid-lowering drugs (LLDs). DESIGN: Observational study focusing on LLD use before (1994-98) and after an intervention (1999). SETTING: Guidelines were developed by the Danish College of General Practitioners and focused on prevention of cardiovascular heart disease (CHD). Guidelines were sent out and changes in reimbursement took place in December 1998. Prescriptions for LLDs were extracted from a population-based prescription database (Odense University Pharmacoepidemiological Database, OPED) covering 10% of the Danish population (470,000 inhabitants). MAIN OUTCOME MEASURES: Incidence rate and 1 year prevalence rate (annual prevalence) of LLD use. RESULTS: The incidence of LLD use increased significantly in the year following the intervention. Incidence rate ratio (after/before) was 1.43 (CI 1.35-1.52). The annual prevalence of LLD use in the population increased by 0.4% after the intervention (0.2% before). The corresponding figure for patients with diabetes mellitus (treated with insulin or oral anti-diabetics) was 2.3% after the intervention (1.2% before), and for patients with CHD (treated with vasodilators) 8.1% after the intervention (5.0% before). CONCLUSION: Guidelines accompanied by a change in reimbursement rules had a significant influence on the prescribing of lipid-lowering drugs.

Aged↗

Cost-effectiveness analysis of intravascular ultrasound guided percutaneous coronary intervention versus conventional percutaneous coronary intervention.

OBJECTIVE: Investigation of the cost-effectiveness of intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI) compared to PCI guided by coronary angiography (CAG). METHODS: One hundred and eight men referred for PCI, were randomized to IVUS or CAG guided PCI. After 6 months, the patients were subjected to a study related clinical and invasive follow-up investigation by CAG, IVUS and intracoronary Doppler flow measurements. Incremental costs of IVUS guided procedures and costs of re-interventions were estimated using the Activity Based Costing (ABC) method. RESULTS: Patients randomized to IVUS guided PCI experienced an improved clinical outcome, with lower angina levels than patients in the CAG guided group. The initial cost of performing IVUS guidance was increased due to extra procedure time, IVUS catheters and slightly more balloons and stents, but fewer patients in the IVUS guided group needed re-intervention. Overall, these savings outweighed the initial cost increase. CONCLUSION: Our data suggest that when performing IVUS guided PCI, costs as well as benefits increase. The increased benefits measured as cost savings resulting from less restenosis outweigh the cost increase from performing the IVUS guided PCI as opposed to CAG guided PCI.

Adult↗

What does it take to collaborate with families affected by brain injury? A preliminary model.

BACKGROUND: Collaboration refers to a process in which family expertise is acknowledged and used to direct selection, implementation, and evaluation of treatment plans. Although the skills required to create collaborative partnerships with families are a mainstay of practice for certain rehabilitation disciplines, others have traditionally worked in client-clinician dyads that emphasize the role of the professional as responsible for client change. In addition, the existing collaborative models for working with families affected by brain injury require intensive resources and supports, making collaborative partnerships difficult to create within today's clinical and educational service delivery environments. RESULT: In this article, we report our efforts to create an accessible set of collaboration procedures for rehabilitation professionals working in clinical and educational settings with individuals with brain injury and their families. A 2-year, qualitative study with eight families led to the development of a preliminary model and prescriptive manual for applying collaborative principles to practice. CONCLUSION: We review the components of the model and implications for practice.

Adolescent↗

Age, gender, and autonomic tone effects on surface electrocardiographic indices of ventricular repolarization.

BACKGROUND: Prolonged QT offset dispersion (QToD), an index of heterogeneity of ventricular repolarization, is thought to be an independent predictor of all-cause and cardiovascular mortality. However the influence of gender and autonomic tone in healthy adults on age-related changes in measures of ventricular repolarization are not well characterized. METHODS: QToD and T wave complexity were measured in 56 healthy subjects with no detectable heart disease (by echo and stress test)-38 young subjects with a mean age of 28 +/- 4 years and 18 old subjects with a mean age of 71 +/- 7 years. QToD and T wave complexity were computed from 12-lead ECGs using the GE Marquette QT Guard automated analysis program with manual overreading at rest (baseline), following exercise, and double autonomic blockade with atropine and propranolol. Data was analyzed using factorial ANOVA. RESULTS: Young males had a significantly greater QToD than young and old females at baseline (28 +/- 5 ms, 23 +/- 5 ms, and 22 +/- 5 ms, respectively, P < 0.01), an intrinsic effect independent of changes in autonomic tone. In contrast, females had significantly greater T wave complexity than males following exercise and double autonomic blockade with a definite trend at baseline. There was no correlation between T wave complexity and QToD. CONCLUSIONS: Age and gender demonstrate a complex interaction on indices of myocardial repolarization with different measures behaving differently. These findings have implications for better understanding age and gender effects on myocardial electrophysiology.

Adult↗

High resolution comparative genomic hybridization detects 7-8 megabasepair deletion in PCR amplified DNA.

We investigated if any change in spatial resolution of comparative genomic hybridization analysis could be detected when using DNA amplified by degenerate oligonucleotide primed PCR (DOP-PCR) as opposed to the use of unamplified DNA. Five DNA samples from B-cell leukemias with small 11q deletions were amplified by DOP-PCR and analysed by means of high resolution comparative genomic hybridization (HR-CGH) for the evaluation of aberration size detection limit. By means of HR-CGH, we found the detection limit of DOP-PCR CGH for deletions to be between 3 Mbp and 7-8 Mbp.

Chromosomes, Human, Pair 11↗

Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment.

OBJECTIVE: To assess the efficacy and safety of glucagon-like peptide-1 (GLP-1) on the plasma glucose level when given as a continuous infusion for either 16 or 24 h per day to type 2 diabetic patients who were poorly controlled on sulfonylurea treatment. RESEARCH DESIGN AND METHODS: This single-center, randomized, parallel, double-blind, placebo-controlled trial was conducted in 40 hospitalized patients who were randomized to receive infusions of either placebo or GLP-1 4 or 8 ng. kg(-1). min(-1) for either 16 or 24 h per day for 7 days. At predetermined intervals, 24-h profiles of glucose, glucagon, and insulin were measured. Adverse events and clinical chemistry and hematology were recorded. RESULTS: For all active treatment groups, the change in average glucose (area under the curve [AUC] for day 7 minus AUC for day 0 divided by 24 h) was statistically significantly different from placebo (P < or = 0.001). The GLP-1 8 ng. kg(-1). min(-1) dose given for 24 h was more efficacious than any of the other doses (P < or = 0.05). Nocturnal and fasting plasma glucose levels at day 7 were greater in the 16-h groups compared with the 24-h groups (P < or = 0.05). Insulin AUC did not show any treatment effect for any of the treatment groups when change was assessed from day 0 to day 7. However, for the 16-h groups, the pattern of the insulin profiles changed; the insulin profiles were considerably higher during the initial 3-4 h after restart of the GLP-1 infusion on day 7, although there was a tendency for insulin levels to decrease during the afternoon and evening. Glucagon AUC decreased significantly for all active treatment groups compared with placebo. GLP-1 was generally well tolerated. CONCLUSIONS: This study demonstrated that GLP-1 should be given continuously to obtain the most optimal glycemic control. Because of the short plasma half-life of native GLP-1, long-acting derivatives should be developed to make GLP-1 treatment clinically relevant.

Adult↗

Birth of live calves by in vitro embryo production of slaughtered cows in a commercial herd in South Africa.

In vitro fertilisation (IVF) has become a useful breeding tool in most of the developed world. In this paper the success of bovine IVF and the birth of live calves under typical South African conditions is reported. Oocytes for IVF were collected from the ovaries of 6 slaughtered Bovelder beef cows. On average, 36.2 oocytes per donor were retrieved. From these oocytes, 43 blastocysts were produced from 5 of the donors by IVF with frozen Bovelder semen. The best 11 of these embryos were transferred into oestrous, synchronised Bovelder recipients in the same herd. As a result, 7 calves were born (a 64% calving rate) from 4 of the original donors. The calves had a normal birth mass, but the mean gestation length of the male calves was significantly longer than the herd average (291.6 versus 285.2 days respectively). No calving difficulties were encountered. In summary, it was shown that IVF for bovine embryo production and transfer is possible on a commercial basis in South Africa.

Abattoirs↗