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Biomedical subjects

H Olsen

Publications and source records attributed to H Olsen.

At least 19 recordsLinked to original sources
PubMed2006

Doxorubicin levels in the serum and ascites of patients with ovarian cancer.

AIMS: To investigate the diffusion and accumulation of doxorubicin metabolites in the ascites of patients with ovarian cancer following intravenous injection, as a model for intraperitoneal accumulation of drugs. METHODS: The concentrations of doxorubicin and its metabolites [Doxorubicinol (Dox-ol), 7-deoxydoxorubicinolone (7d-Dox-ol-on) and 7-deoxydoxorubicinone (7d-Dox-on)] were measured using high-performance liquid chromatography in the serum and in the ascites of seven patients with recurrent ovarian carcinoma suffering from symptomatic ascites and treated with intravenous doxorubicin. RESULTS: Doxorubicin metabolites accumulated in the peritoneal cavity. The concentrations of the doxorubicin metabolites were initially higher in the serum compared to the ascitic fluid, but following several hours the doxorubicin metabolites became higher in the ascites, and remained detectable in the ascites for up to 168h, long after disappearance from the serum. CONCLUSIONS: Doxorubicin metabolites accumulate in the ascites and are cleared more slowly from the peritoneal compartment than from the serum. Accumulation in the peritoneal cavity with prolonged half-life should be considered when administering medication in patients with ascites.

Adult↗
PubMed2003

Influence of glucose and insulin on transcapillary fluid absorption from the arm during lower body negative pressure in man.

This study examined the influence of insulin and glucose on the transcapillary fluid absorption during lower body negative pressure (LBNP) in humans. Ten healthy males [23 (1) years] were exposed to LBNP of 45 cmH(2)O on two occasions: (1) before and during a hyperinsulinaemic clamp (HI) and (2) before and during a hyperglycaemic clamp (HG). Transcapillary fluid absorption and blood flow were recorded with volumetric technique. Forearm blood flow increased during HI from 2.3 (0.3) ml (100 ml)(-1) min(-1) to 3.3 (0.5) ml (100 ml)(-1) min(-1) ( P<0.05). The haemodynamic response to LBNP was similar during HI and HG compared with control LBNP. Transcapillary fluid absorption during LBNP increased during HG from 0.044 (0.007) ml (100 ml)(-1) min(-1) to 0.059 (0.009) ml (100 ml)(-1) min(-1 )( P<0.01), whereas it was unchanged during HI. In conclusion, hyperglycaemia augments transcapillary fluid absorption from skeletal muscle and skin during LBNP whereas hyperinsulinaemia has no such effect. This indicates that in human hyperglycaemia contributes to plasma volume restitution during hypovolaemic circulatory stress.

Absorption↗
PubMed2003

Cell volume regulation: osmolytes, osmolyte transport, and signal transduction.

In recent years, it has become evident that the volume of a given cell is an important factor not only in defining its intracellular osmolality and its shape, but also in defining other cellular functions, such as transepithelial transport, cell migration, cell growth, cell death, and the regulation of intracellular metabolism. In addition, besides inorganic osmolytes, the existence of organic osmolytes in cells has been discovered. Osmolyte transport systems-channels and carriers alike-have been identified and characterized at a molecular level and also, to a certain extent, the intracellular signals regulating osmolyte movements across the plasma membrane. The current review reflects these developments and focuses on the contributions of inorganic and organic osmolytes and their transport systems in regulatory volume increase (RVI) and regulatory volume decrease (RVD) in a variety of cells. Furthermore, the current knowledge on signal transduction in volume regulation is compiled, revealing an astonishing diversity in transport systems, as well as of regulatory signals. The information available indicates the existence of intricate spatial and temporal networks that control cell volume and that we are just beginning to be able to investigate and to understand.

Animals↗
PubMed2001

Organochlorine pesticides, polychlorinated biphenyls, and butyltin compounds in blubber and livers of stranded California sea lions, elephant seals, and harbor seals from coastal California, USA.

Concentrations of polychlorinated biphenyls (PCBs), DDTs (p,p'-DDE, p,p'-DDD, p,p'-DDT), chlordanes (CHLs; cis-chlordane, cis-nonachlor, trans-nonachlor, and oxychlordane), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), tris(4-chlorophenyl)methane (TCPMe), tris(4-chlorophenyl)methanol (TCPMOH), and mono- (MBT), di-(DBT), and tri-butyltin (TBT) were determined in blubber and livers of 15 California sea lions (Zalophus californianus), 6 northern elephant seals (Mirounga augustirostris), and 10 harbor seals (Phoca vitulina) found stranded along the coasts of California, USA, during 1991-1997. Among the organochlorines analyzed, DDTs were predominant, followed in decreasing order by PCBs, CHLs, TCPMe, TCPMOH, HCHs, and HCB. The greatest concentrations of organochlorines were found in California sea lions. The highest DDT and PCB concentrations found in the blubber of California sea lions were 2,900 and 1,300 microg/g, lipid weight, respectively. Concentrations of TCPMe and TCPMOH in California sea lions were correlated significantly with DDT concentrations. Concentration ratios of various organochlorines in harbor seal livers were different from those in California sea lions and elephant seals, which suggested that the sources of exposure of harbor seals to organochlorines were different from those in the other two species. Concentrations of butyltin compounds in livers of pinniped species ranged from 2 to 99 ng/g, wet weight, which were less than those observed in cetaceans and in California sea otters.

Adipose Tissue↗
PubMed2001

Rapid discrimination among individual DNA hairpin molecules at single-nucleotide resolution using an ion channel.

RNA and DNA strands produce ionic current signatures when driven through an alpha-hemolysin channel by an applied voltage. Here we combine this nanopore detector with a support vector machine (SVM) to analyze DNA hairpin molecules on the millisecond time scale. Measurable properties include duplex stem length, base pair mismatches, and loop length. This nanopore instrument can discriminate between individual DNA hairpins that differ by one base pair or by one nucleotide.

Bacterial Proteins↗
PubMed2001

Blood pressure levels in treated hypertensive patients in general practice in Norway.

The aim of this study was to examine the blood pressure (BP) levels in patients treated for essential hypertension in 1816 patients in general practice in Norway. The study was based on an optical readable questionnaire filled out by the physician including information about systolic (S) and diastolic (D) BP, gender, age, body weight, smoking habits and all pharmaceutical treatment given. Sixty-four per cent of the patients were treated with one antihypertensive drug. Only 22.3% of the women and 30.7% of the men (p < 0.05) had BP < or = 140/90 mmHg. When BP < 160/95 was used as criterion for BP control, the fraction of patients was 50%. The fraction of patients with DBP < or = 80 mmHg was 26% in the whole group of patients. DBP < or = 90 mmHg was achieved in 74% and SBP < or = 140 mmHg in 30% of the patients. The BP control was less in women and in patients above 60 years of age. Patients on combination therapy were no better controlled than those on monotherapy. Based on our results, the proportion of hypertensive patients on drug treatment with insufficient BP control is too high. Efforts should be made to improve the medical treatment of hypertension in general practice in Norway.

Age Factors↗
PubMed2000

A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity.

As part of a large scale effort to discover novel secreted proteins, a cDNA encoding a novel cytokine was identified. Alignments of the sequence of the new protein, designated IL-17B, suggest it to be a homolog of the recently described T cell-derived cytokine, IL-17. By Northern analysis, EST distribution and real-time quantitative polymerase chain reaction analysis, mRNA was detected in many cell types. A novel type I transmembrane protein, identified in an EST data base by homology to IL-17R, was found to bind specifically IL-17B, as determined by surface plasmon resonance analysis, flow cytometry, and co-immunoprecipitation experiments. Readily detectable transcription of IL-17BR was restricted to human kidney, pancreas, liver, brain, and intestines and only a few of the many cell lines tested. By using a rodent ortholog of IL-17BR as a probe, IL-17BR message was found to be drastically up-regulated during intestinal inflammation elicited by indomethacin treatment in rats. In addition, intraperitoneal injection of IL-17B purified from Chinese hamster ovary cells caused marked neutrophil migration in normal mice, in a specific and dose-dependent manner. Together these results suggest that IL-17B may be a novel proinflammatory cytokine acting on a restricted set of target cell types. They also demonstrate the strength of genomic approaches in the unraveling of novel biological pathways.

Adjuvants, Immunologic↗
PubMed2000

[Prescription patterns of antihypertensive agents in general practice in 1995].

BACKGROUND: Hypertension represents a risk factor in the development of cardiovascular disease. MATERIAL AND METHODS: The prescription of antihypertensive drugs and the daily doses used were examined in a questionnaire-based survey among 2,586 drug-treated hypertensive patients who attended a general practitioner for clinical control in November 1995. RESULTS: The proportion of patients treated with one antihypertensive drug only was 63%. ACE inhibitors, alpha blockers and angiotensin-II antagonists constituted 22.7%, 6.6% and 4.4%, and betablockers, calcium channel blockers and diuretics 21.7%, 23.7% and 16.3% of the prescriptions respectively. Women were more often prescribed diuretics than men, and older individuals more often than younger persons. No striking difference in the prescription of antihypertensive drugs were observed between the five health regions of Norway. There was no reduction in the prescribed daily doses of antihypertensives used in combination therapy compared with monotherapy. In approximately one quarter of the prescriptions there was a positive correlation between the prescribed daily dose and the patient's weight. The number of antihypertensives prescribed did positively correlate with the patient's weight. INTERPRETATION: This survey shows that antihypertensives without any documented effect on morbidity and mortality were frequently prescribed for hypertension in general practice. Except for the low proportion of diuretic users among elderly patients, our results is in accordance with the Guidelines from the Norwegian Society of General Practitioners.

Adult↗
PubMed2000

Reduced capillary hydraulic conductivity in skeletal muscle and skin in Type I diabetes: a possible cause for reduced transcapillary fluid absorption during hypovolaemia.

AIMS/HYPOTHESIS: Patients with Type I (insulin-dependent) diabetes mellitus have a reduced transcapillary fluid absorption from skeletal muscle and skin and thus defective plasma volume regulation during hypovolaemia. Our aim was to find whether a defective capillary filtration coefficient or impaired transcapillary driving force are aetiologic factors for this reduction. METHODS: We investigated 11 diabetic patients (diabetes duration 6.9 +/- 1.1 years, age 26 +/- 1 years), without complications and 12 control subjects (26 +/- 1 years). Their capillary filtration coefficient was measured in the upper arm using a volumetric technique at rest and during lower body negative pressure (LBNP). We calculated the driving force for transcapillary fluid transfer. RESULTS: The increase in heart rate and the decrease in systolic blood pressure during lower body negative pressure were similar in diabetic and control subjects. The resting capillary filtration coefficient was decreased in the diabetic subjects, 0.033 +/- 0.003 vs 0.051 +/- 0.007 ml x 100 ml(-1) x min(-1) x mmHg(-1) (p < 0.05). During lower body negative pressure, the capillary filtration coefficient increased 35 % in both groups compared with resting capillary filtration coefficient and was still decreased in diabetes; 0.046 +/- 0.004 compared with 0.069 +/- 0.006 ml x 100ml(-1) x min(-1) x mmHg(-1) (p < 0.01). The established driving force during lower body negative pressure was 1.37 +/- 0.11 vs 1.30 +/- 0.15 mmHg (NS) in diabetic and control subjects, respectively. CONCLUSIONS/INTERPRETATION: Our study indicates that a reduced capillary filtration coefficient rather than defective regulation of transcapillary driving force, is the reason for the reduced transcapillary fluid absorption during hypovolaemic circulatory stress found in Type I diabetic patients.

Adult↗
PubMed2000

Cardiovascular response to acute hypovolemia in relation to age. Implications for orthostasis and hemorrhage.

Venous compliance in the legs of aging man has been found to be reduced with decreased blood pooling (capacitance response) in dependent regions, and this might lead to misinterpretations of age-related changes in baroreceptor function during orthostasis. The hemodynamic response to hypovolemic circulatory stress was studied with the aid of lower-body negative pressure (LBNP) of 60 cmH(2)O in 33 healthy men [18 young (mean age 22 yr) and 15 old (mean age 65 yr)]. Volumetric technique was used in the study of capacitance responses in the calf and arm as well as transcapillary fluid absorption in the arm. LBNP led to smaller increase in heart rate (P < 0.001) and peripheral resistance (P < 0.01) and reduced transcapillary fluid absorption in the arm (P < 0.05) in old subjects. However, blood pooling in the calf was reduced in old subjects (1.66 +/- 0.10 vs. 2.17 +/- 0.13 ml/100 ml tissue; P < 0. 01). Accordingly, during similar blood pooling in the calf (LBNP 80 cmH(2)O in old subjects), no changes in cardiovascular reflex responses with age were found. The capacitance response in the arm (mobilization of peripheral blood to the central circulation) was still reduced, however (0.67 +/- 0.10 vs. 1.37 +/- 0.11 ml/100 ml tissue; P < 0.01). Thus the reduced cardiovascular reflex response found in the elderly during orthostatic stress seems to be caused by a reduced capacitance response in the legs with age and a concomitant smaller central hypovolemic stimulus rather than a reduced efficiency of the reflex response. With similar hypovolemic circulatory stress, no changes in cardiovascular reflex responses are seen with age. The capacitance response in the arm (mobilization of peripheral blood toward the central circulation) is reduced, however, by approximately 50% in the elderly. This might seriously impede the possibility of survival of an acute blood loss.

Acute Disease↗
PubMed1999

[Pharmacists' and general practitioners' views on parallel import of drugs].

Since 1995, parallel import of drugs to Norway has been allowed under the European Economic Area Agreement. The health authorities have stated that there are no concerns connected with the use of parallel-imported drugs. This study is an interview survey among general practitioners, pharmacy staff and pharmacists working in pharmacies. The findings show that 91% of the pharmacies dispense parallel-imported drugs and that there is a certain amount of scepticism regarding the use of parallel-imported drugs. Most respondents feel that parallel-imported pharmaceuticals may have financial advantages for the individual patient and economic advantages for society at large, but 50% of the pharmacists and 54% of the physicians were of the opinion that parallel-imported pharmaceuticals represented an increased medical risk for the patients. Approximately 15% of doctors and pharmacy staff had knowledge of either incorrect treatment or adverse drug reactions due to the use of parallel-imported drugs. The time used for prescribing and dispensing parallel-imported drugs is longer than for directly imported preparations. The survey shows that approximately every fifth doctor will use the right of reservation in connection with the dispensing of parallel-imported drugs, whereas approximately every fourth pharmacist will disregard the right of reservation.

Drug Costs↗
PubMed1999

Gene expression and production of the monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils.

Monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein of 10 kDa (IP-10) are related members of the CXC chemokine subfamily that bind to a common receptor, CXCR3, and that are produced by different cell types in response to IFN-gamma. We have recently reported that human polymorphonuclear neutrophils (PMN) have the capacity to release IP-10. Herein, we show that PMN also have the ability to produce MIG and to express I-TAC mRNA in response to IFN-gamma in combination with either TNF-alpha or LPS. While IFN-gamma, alone or in association with agonists such as fMLP, IL-8, granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, failed to influence MIG, IP-10, and I-TAC gene expression, IFN-alpha, in combination with TNF-alpha, LPS, or IL-1beta, resulted in a considerable induction of IP-10 release by neutrophils. Furthermore, IL-10 and IL-4 significantly suppressed the expression of MIG, IP-10, and I-TAC mRNA and the extracellular production of MIG and IP-10 in neutrophils stimulated with IFN-gamma plus either LPS or TNF-alpha. Finally, supernatants harvested from stimulated PMN induced migration and rapid integrin-dependent adhesion of CXCR3-expressing lymphocytes; these activities were significantly reduced by neutralizing anti-MIG and anti-IP-10 Abs, suggesting that they were mediated by MIG and IP-10 present in the supernatants. Since MIG, IP-10, and I-TAC are potent chemoattractants for NK cells and Th1 lymphocytes, the ability of neutrophils to produce these chemokines might contribute not only to the progression and evolution of the inflammatory response, but also to the regulation of the immune response.

Apoptosis↗
PubMed1999

[Methadone used in the treatment of opioid dependence].

Norway has been a stronghold of restrictive attitudes and scepticism towards the use of methadone in treatment of heroin addiction. A policy of nation-wide use of methadone has now been adopted. This paper gives a short history of the use of methadone, a review of present neurobiological knowledge and a description of the different approaches in methadone based treatment. Methadone treatment does not reduce opioid dependency but compensates for neurobiological complications of long-term use. This increases the ability to profit from psychosocial approaches in treatment and reduces the tendency to risk-taking and socially disturbing behaviour. Norway aims to follow the "Swedish" model in methadone policy with emphasis on high threshold, high dose treatment combined with control and systematic rehabilitative measures. This choice should be evaluated both in a comparative and in a treatment oriented perspective.

Heroin Dependence↗
PubMed1999

Regulation of human IL-18 mRNA expression.

As virtually nothing is known about the pattern of expression of human IL-18, we investigated certain factors that may contribute to the regulation of IL-18 mRNA accumulation and compared this with regulation of the human gene encoding the p40 chain of IL-12, a cytokine that shares similar biologic activity with IL-18. IL-18 mRNA was expressed constitutively in unstimulated PBMC or monocytes, unlike p40, which required induction by a stimulus. Upon stimulation, IL-18 transcript accumulation was enhanced with an earlier and more transient pattern of expression than IL-12 p40 mRNA. Bacteria-derived stimuli and priming with IFN-gamma or IL-4 also upregulated IL-18 mRNA in a fashion similar to that of IL-12 p40. IL-10 exerted an inhibitory effect on IL-18 mRNA accumulation, though not as markedly as in the suppression of IL-12 p40 by IL-10. Finally, unlike IL-12 p40 mRNA, the constitutive accumulation of IL-18 transcripts by unstimulated cells was amplified in the presence of the translational blocker cycloheximide, which also caused a superinduction of IL-18 expression after Staphylococcus aureus stimulation.

Blotting, Northern↗
PubMed1999

Hsp60-induced tolerance in the rotifer Brachionus plicatilis exposed to multiple environmental contaminants.

Hsp60 induction was selected as a sublethal endpoint of toxicity for Brachionus plicatilis exposed to a water accommodated fraction (WAF) of Prudhoe Bay crude oil (PBCO), a PBCO/dispersant (Corexit 9527(R)) fraction and Corexit 9527(R) alone. To examine the effect of multiple stressors, exposures modeled San Francisco Bay, where copper levels are approximately 5 microgram/L, salinity is 22 per thousand, significant oil transport and refining occurs, and petroleum releases have occurred historically. Rotifers were exposed to copper at 5 microgram/L for 24 h, followed by one of the oil/dispersant preparations for 24 h. Batch-cultured rotifers were used in this study to model wild populations instead of cysts. SDS-PAGE with Western Blotting using hsp60-specific antibodies and chemiluminescent detection were used to isolate, identify, and measure induced hsp60 as a percentage of control values. Both PBCO/dispersant and dispersant alone preparations induced significant levels of hsp60. However, hsp60 expression was reduced to that of controls at high WAF concentrations, suggesting interference with protein synthesis. Rotifers that had been preexposed to copper maintained elevated levels of hsp60 upon treatment with WAF at all concentrations. Results suggest that induction of hsp60 by chronic low-level exposure may serve as a protective mechanism against subsequent or multiple stressors and that hsp60 levels are not additive for the toxicants tested in this study, giving no dose-response relationship. The methods employed in this study could be useful for quantifying hsp60 levels in wild rotifer populations.

Animals↗
PubMed1999

Reduced transcapillary fluid absorption from skeletal muscle and skin during hypovolaemia in insulin-dependent diabetes mellitus.

OBJECTIVES: Diabetes mellitus is associated with a high cardiovascular morbidity which has been linked to disturbances in microvascular function. This study was designed to examine the transcapillary fluid absorption during experimental hypovolaemia in type 1 diabetes. SUBJECTS: Twelve males with type 1 diabetes (age 25 +/- 3 years, duration 8 +/- 1 years) with no clinical microangiopathy and 12 healthy males (22 +/- 2 years). INTERVENTIONS: As a model for hypovolaemic circulatory stress, lower body negative pressure (LBNP: 15, 30 and 60 cmH2O) was used. Transcapillary fluid absorption from tissue to blood in the upper arm, as well as forearm blood flow, was measured by volumetric technique. RESULTS: Resting forearm blood flow, heart rate and blood pressure were similar in diabetic patients and controls. Basal plasma noradrenaline was reduced in the diabetics compared with controls (0.75 +/- 0.06 vs. 1.09 +/- 0.10 pmol L-1, P < 0.05), but the increase in plasma noradrenaline in response to LBNP was similar in the two groups. The haemodynamic responses to LBNP in the two groups were equal, showing a reduction of pulse pressure, an increase in heart rate and in peripheral resistance with a concomitant blood flow reduction. The transcapillary fluid absorption (mL 100 mL-1 min-1) was significantly reduced in the diabetic patients: LBNP 15 cmH2O, 0.024 +/- 0.004 vs. 0.036 +/- 0. 002; 30 cmH2O, 0.041 +/- 0.003 vs. 0.056 +/- 0.005; and 60 cmH2O, 0. 057 +/- 0.007 vs. 0.091 +/- 0.008 (diabetic patients vs. controls, P < 0.001). CONCLUSIONS: The transcapillary fluid absorption from tissue to blood during hypovolaemic circulatory stress in type 1 diabetic patients is reduced by one-third compared with controls, which indicates impaired plasma volume regulation. This basic mechanism for plasma volume control is affected before clinical microcirculatory complications are found and could be one of the causes of the increased cardiovascular morbidity and mortality in IDDM.

Adult↗