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Biomedical subjects

P Nilsson

Publications and source records attributed to P Nilsson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Pharmacokinetics and safety of FFR-rFVIIa after single doses in healthy subjects.

FFR-rFVIIa is an antithrombotic agent, which has also proven to have antirestenotic properties in animal models. FFR-rFVIIa is a modified recombinant FVIIa in which the catalytic site is irreversibly inactivated by a synthetic tripeptide covalently bound with the FVIIa molecule. The modified rFVIIa retains its tissue factor (TF) binding capacity but is otherwise enzymatically inactive. A double-blind, placebo-controlled, randomized dose escalation trial was conducted to investigate eight single i.v. doses of FFR-rFVIIa (0.01, 0.02, 0.05, 0.08, 0.12, 0.18, 0.27, or 0.40 mg/kg body weight) in healthy male volunteers (n = 62). Safety, pharmacokinetics, and pharmacodynamics of FFR-rFVIIa were assessed. Mean (SD)AUC0-infinity ranged from 0.35 (0.11) to 28.8 (3.5)microg.h/ml, and mean Cmax ranged from 0.078 (0.019) to 4.8 (0.7) microg/ml. The mean elimination half-life ranged from 3.8 to 5.8 hours. Mean AUC0-infinity increased with increasing dose levels. Cmax appeared to be proportional to the dose level, with the exception of the lowest dose level. A dose-dependent prolongation of the prothrombin time was found, demonstrating that FFR-rFVIIa inhibited coagulation via the TF-dependent pathway FFR-rFVIIa was generally well tolerated at all dose levels studied.

Adolescent↗
PubMed2001

What is the optimal blood pressure in patients with diabetes mellitus?

Cardiovascular disease is the number one cause of death in patients with type 2 diabetes mellitus. This condition leads to an increased risk of premature mortality in patients with ischemic heart disease and stroke. Many risk factors besides hyperglycemia in itself contribute to this increased risk, acting in a synergistic fashion. One of the most important risk factors is hypertension. Several recent clinical trials have shown the benefits of reducing high blood pressure in patients with diabetes mellitus to lower levels than have previously been recommended in clinical guidelines. In both the United Kingdom Prospective Diabetes Study (UKPDS) and the Hypertension Optimal Treatment (HOT) study a significant trend for increased benefits associated with lower diastolic blood pressure levels was shown. Therefore, clinicians should be encouraged to do more to treat hypertension in patients with type 2 diabetes mellitus and increase the proportion of patients in whom acceptable blood pressure control is achieved. For example, in Sweden, acceptable blood pressure control is currently only achieved in about 20 to 25% of patients with type 2 diabetes mellitus. Recent evidence also points to the primary importance of a tight blood pressure control. This implies drug combination treatment for the majority of patients. Therefore, the clinician must be able to use a broad variety of antihypertensive drugs, and from these drugs choose alternative combinations with pharmacological synergism.

Adrenergic beta-Antagonists↗
PubMed2001

Intracerebral microdialysis in neurointensive care: the use of urea as an endogenous reference compound.

OBJECT: When evaluating the results of intracerebral microdialysis, the in vivo performance of the microdialysis probe must be considered, because this determines the fraction of the interstitial concentration obtained in the microdialysis samples. The in vivo performance is dependent on several factors, for example, the interstitial compartment's diffusion characteristics, which may vary during the course of the acute brain injury process. In the present study the authors investigated the method of controlling the in vivo performance by using urea, which is evenly distributed in all body fluid compartments, as an endogenous reference compound and by comparing the urea levels in three compartments: the brain (CNS), abdominal subcutaneous tissue (SC), and blood serum (BS). METHODS: Sixty-nine patients with traumatic brain injury or cerebrovascular disease were included in the study. In 63 of these patients a CNS probe was used, an SC probe was used in 40, and both were used in 34. Urea was measured by enzymatic methods, at bedside for the microdialysis samples and in routine clinical laboratory studies for the BS samples, with the probe calibrated to give identical results. The correlation coefficient for CNS/SC urea was 0.88 (2414 samples), for CNS/BS urea it was 0.89 (180 samples), and for SC/BS urea it was 0.98 (112 samples). CONCLUSIONS: Urea levels in the CNS, SC, and BS were highly correlated, which supports the assumption that urea is evenly distributed. The CNS/SC urea ratio can therefore be used for monitoring the CNS probe's in vivo performance. Fluctuations in other substances measured with microdialysis are probably caused by biological changes in the brain, as long as the CNS/SC urea ratio remains constant.

Adipose Tissue↗
PubMed2001

[Swedish research in hypertension].

In Sweden, research in hypertension has been on-going since the early 1920's when Eskil Kylin was the first to describe hypertension as part of a metabolic cardiovascular syndrome. Later on several other researchers and clinicians have contributed to the development of medical understanding of hypertension and its treatment. Bertil Hood was the one who started modern drug therapy for malignant hypertension in 1950 when hexamethonium was used, which was a life-saving drug but with many serious adverse reactions. Later on other drugs have been developed many of them first tested in smaller haemodynamic studies before used in clinical trials. Some of these smaller studies were initiated by Lars Werkö and his colleagues. In recent years Swedish researchers have made great contributions in hypertension research, e.g. Björn Folkow for studies regarding arterial wall modelling in hypertension, and Lennart Hansson for initiating large-scale randomised clinical trials in middle-aged and elderly hypertensive patients. In spite of the fact that hypertensive patients constitute the largest patient group of all, with currently 700.000 treated patients in Sweden, it is still not well established which therapy and other interventions are the most beneficial and cost-effective for long-term treatment. Swedish research in hypertension is therefore ongoing and supported by the Swedish Hypertension Society for which Peter Nilsson is the current patient.

History, 20th Century↗
PubMed2000

Observation of direct photons in central 158A GeV (208)P(208)b+Pb collisions

A measurement of direct photon production in 208Pb+208Pb collisions at 158A GeV has been carried out in the CERN WA98 experiment. The invariant yield of direct photons in central collisions is extracted as a function of transverse momentum in the interval 0.5 1.5 GeV/c. The result constitutes the first observation of direct photons in ultrarelativistic heavy-ion collisions. It could be significant for diagnosis of quark-gluon-plasma formation.

Journal Article↗
PubMed2000

Design and dosimetry characteristics of a soft-docking system for intraoperative radiation therapy.

PURPOSE: The design concept and the dosimetric characteristics of an applicator system for intraoperative radiation therapy (IORT) with special emphasis on alignment methods, the effect of a plastic scatterer in the beam, radiation leakage, and misalignment dosimetry, are presented in this paper. MATERIALS AND METHODS: A soft-docking system for a linear accelerator, which enables collimation of electron beams (4-22 MeV) for IORT has been developed. The system includes twenty-one circular polymethylmethacrylate (PMMA) treatment cones of different lengths, diameters and end angles. All in-water measurements are made using p-type silicon diode detectors. RESULTS: The effect of introducing a PMMA scatterer in the therapeutic beam includes increased surface dose values (above 83% for all nominal electron energies and for all cones) and improved dose homogeneity within the therapeutic range. Electrons scattered from the inside wall of the cone result in dose profile horns at depth of dose maximum always lower than 109%. The radiation leakage outside the cone is less than 13%. Large changes in the dose profiles occur if the intraoperative cone is misaligned more than 0.5. CONCLUSION: The alignment procedure of the soft-docking system is easy to handle and the applicator design provides adequate collimation of electron beams for IORT.

Combined Modality Therapy↗
PubMed2000

Luminescence control in the marine bacterium Vibrio fischeri: An analysis of the dynamics of lux regulation.

A mathematical model has been developed based on the fundamental properties of the control system formed by the lux genes and their products in Vibrio fischeri. The model clearly demonstrates how the components of this system work together to create two, stable metabolic states corresponding to the expression of the luminescent and non-luminescent phenotypes. It is demonstrated how the cell can "switch" between these steady states due to changes in parameters describing metabolic processes and the extracellular concentration of the signal molecule N-3-oxohexanoyl-l-homoserine lactone. In addition, it is shown how these parameters influence how sensitive the switch mechanism is to cellular LuxR and N-3-oxohexanoyl-l-homoserine lactone and complex concentration. While these properties could lead to the collective phenomenon known as quorum sensing, the model also predicts that under certain metabolic circumstances, basal expression of the lux genes could cause a cell to luminesce in the absence of extracellular signal molecule. Finally, the model developed in this study provides a basis for analysing the impact of other levels of control upon lux regulation.

4-Butyrolactone↗
PubMed2000

[Evidence-based treatment of hypertension in type 2-diabetes. New studies support active blood pressure reduction].

Tre treatment of hypertension in type 2 diabetes in currently much in focus. The aim of this treatment is to prevent cardiovascular disease by reducing the mean blood pressure level to less than 140/85 mm Hg in all patients who do not experience orthostatic reactions. In most patients it seems as if the strict blood pressure control is more important for the prognosis than the choice made of specific drug therapy. Nevertheless, specific pharmacological properties may be of special importance for some patients. During the last few years several new randomised trials have increased our knowledge for an approach based on evidence-based medicine towards hypertension in type 2 diabetes. These studies are summarized and discussed in this paper. Of particular importance is that normally a combination-therapy is needed in the vast majority of patients. Synergistic drugs should therefore be combined to achieve an optimal blood pressure control with a minimum of side effects.

Antihypertensive Agents↗
PubMed2000

Multi-centre assessment of the Spiegelberg compliance monitor: preliminary results.

Acute brain injury states (e.g. head injury, subarachnoid haemorrhage) show clear inverse relationships of ICP vs compliance, with ICP instability at times of lower compliance states. Variance in compliance values is large in hydrocephalus where ICP is relatively lower and compliance higher. Nonetheless, early experience shows that compliance data influence decisions on CSF diversion treatments. Future work will focus on the ability of intracranial compliance to predict ensuing ICP instability and methodological refinement for monitoring patients who have higher compliance states.

Brain↗
PubMed2000

Long-term outcome of the Malmö preventive project: mortality and cardiovascular morbidity.

OBJECTIVES: To analyse the effects on mortality and cardiovascular morbidity in a population-based sample, invited to an intervention programme incorporating a baseline screening examination and treatment programmes for subjects with cardiovascular risk factors, high alcohol intake and, in women, suspicion of breast cancer on mammography. SETTING: Section of Preventive Medicine, Department of Medicine, University Hospital, Malmö, Sweden. SUBJECTS: Birth cohorts (aged 32-51 years) invited to screening examination (men = 9. 923; women = 4.422) were compared to birth cohorts not invited (men = 6.655; women = 4.290). Mean participation rate in the invited cohorts was 71% (range 64-78%). SCREENING EXAMINATION: Between 1974 and 1992 a baseline screening including a physical examination, blood pressure, a questionnaire regarding, e.g. family history, lifestyle, and socio-economic factors, laboratory tests of serum cholesterol, triglycerides, gamma-glutamyl-transferase, blood glucose before and after an oral glucose load, as well as a mammography examination in women, was performed. INTERVENTIONS: Subjects with hypertension; hyperlipidaemia; diabetes or glucose intolerance; high alcohol intake; or, in women, suspicion of breast cancer were referred to special outpatient clinics. MAIN OUTCOME MEASURES: Total and cause-specific mortality, nonfatal myocardial infarction, and stroke, from the screening examination until the end of 1995, was followed in both the intervention and control groups, using national and/or local registries. RESULTS: Total mortality did not differ significantly between the intervention group and control group. Cause-specific deaths were also similar except for 'other' deaths amongst men being significantly lower in the intervention group, mainly due to a lower mortality from 'other' causes (suicide, alcohol related deaths) in men under 40 years of age at baseline. Women under 40 years of age had a significantly lower mortality from cancer in the intervention group than in the control group. Nonfatal myocardial infarction and stroke did not differ between intervention and control group in either sex. Within the invited birth cohorts, nonparticipants had a higher total and cause-specific mortality. CONCLUSIONS: Risk factor screening for major diseases such as cardiovascular disease, alcohol abuse, diabetes mellitus and breast cancer, and subsequent treatment of the detected risk factors/diseases - The Malmö Preventive Project - did not reduce total mortality in the intervention group as a whole. In subjects under 40 years of age at entry, total mortality was lower in the intervention group than in the control group. In men, this seemed to be due to a reduction of alcohol-related deaths, whilst in women death from cancer was reduced.

Adult↗
PubMed2000

Prevention of cardiovascular disease and diabetes: lessons from the Malmö Preventive Project.

Major public health problems such as cardiovascular disease and type 2 diabetes pose a challenge to both the medical profession and the health care system of most Western countries. In spite of widespread knowledge about risk factors and pathophysiological processes, it has been difficult to find effective preventive mass strategies based on evidence from controlled clinical trials. In the Malmö Preventive Project, Sweden, 33 346 subjects were screened for risk factors between 1974 and 1992, and a quarter of them were offered preventive help for cardiovascular disease risk or alcohol abuse. The overall finding of the project was that benefits of screening and prevention on mortality risk could only be shown in certain subgroups of younger men and women, not in the total screened cohort, as compared with a nonscreened reference population. These findings therefore question the effectiveness of preventive methods and drugs used during previous decades. New preventive methods are therefore needed and should be properly evaluated to form a basis for evidence-based prevention (EBP) in cardiovascular medicine.

Cardiovascular Diseases↗
PubMed2000

Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmö, Sweden.

AIMS: To assess whether there is an association between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects free from symptomatic cardiovascular disease. METHODS: A cross-sectional population-based study in Malmö, Sweden, of 4,816 (40% men) subjects, born 1926-1945. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the 75th percentile. Criteria issued by the European Group for the Study of Insulin Resistance (EGIR) were used for the definition of the insulin resistance syndrome. Common carotid artery intima-media thickness (IMT) and carotid stenosis (> 15%) were measured by B-mode ultrasonography. RESULTS: Age and sex-adjusted common carotid IMT among subjects with the insulin resistance syndrome (12.7%) and controls was 0.812 mm, respectively, 0.778 mm (P < 0.001). The prevalence of stenosis in the two groups was 22.9 and 19.2% (P = 0.040). Insulin resistance per se was after adjustment for age and sex associated with increased IMT (0.780 mm vs. 0.754 mm, P < 0.001). This association disappeared, however, when other factors included in the insulin resistance syndrome were taken into account. CONCLUSIONS: Fasting serum insulin covaries with a number of factors and conditions known to influence the development of atherosclerosis. It is concluded that the association between insulin resistance, as assessed by the HOMA method in non-diabetic subjects, and atherosclerosis is explained by its covariance with established risk factors for cardiovascular disease of which hypertension seems to be the most significant.

Aged↗
PubMed2000

Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty.

We performed a randomized double-blind study on the effect of tranexamic acid on postoperative blood loss and blood transfusions in 39 primary THR operations. Tranexamic acid was given at the end of the operation and 3 hours later. Ultrasound examination 1 week later was performed to measure the occurrence of deep hematomas. In contrast to previous findings in knee arthroplasty, the administration of tranexamic acid failed to give a significant reduction in the postoperative blood loss. This lack of effect was possibly related to the fact that the drug was administered too late. In 11 of the 20 patients receiving tranexamic acid, blood transfusion was not necessary, this being the case in 4/19 in the placebo group (p = 0.05). The occurrence of postoperative deep venous thromboses was similar in the tranexamic acid and placebo groups.

Aged↗
PubMed2000

On beam quality and stopping power ratios for high-energy x-rays.

The aim of this work is to quantitatively compare two commonly used beam quality indices, IPR(20/10) and %dd(10)x, with respect to their ability to predict stopping power ratios (water to air), s(w,air), for high-energy x-rays. In particular, effects due to a varied amount of filtration of the photon beam will be studied. A new method for characterizing beam quality is also presented, where the information we strive to obtain is the moments of the spectral distribution. We will show how the moments enter into a general description of the transmission curve and that it is possible to correlate the moments to s(w,air) with a unique and simple relationship. Comparisons with TPR(20/10) and %dd(10), show that the moments are well suited for beam quality specification in terms of choosing the correct s(w,air).

Air↗