Search PubMed⌕ Search

Biomedical subjects

K Hansen

Publications and source records attributed to K Hansen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Determination of drug effect on tumour cells, host animal toxicity and drug pharmacokinetics in a hollow-fibre model in rats.

PURPOSE: Based on the previously published hollow-fibre assay mainly used for early in vivo anticancer drug screening, we wanted to develop an extended hollow-fibre model in which antitumour activity, haematological toxicity and pharmacokinetics could be studied in the same animal. METHOD: The breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in semipermeable hollow fibres. The fibres were implanted subcutaneously into immunocompetent male Sprague Dawley rats, and the rats were treated with 5-fluorouracil (5-FU, 125 mg/kg), epirubicin (EPI, 10 mg/kg) or cyclophosphamide (CP, 120 mg/kg) intraperitoneally, the new cyanoguanidine CHS 828 (375 mg/kg or 75 mg/kg x 5) orally, or vehicle only. After 6 days the fibres were retrieved and the cell density was evaluated. Haematological parameters were monitored and two to four samples per animal were drawn to determine the pharmacokinetic parameters in NONMEM. RESULTS: Drug treatment had generally low effects on the tumour cells. Of the standard drugs (5-FU, EPI and CP), only CP exerted a statistically significant antiproliferative effect. CHS 828 had only a minor effect as a single dose, but divided into five daily doses had a pronounced effect on both cell lines. 5-FU, EPI and CP all caused a marked decrease in leucocytes, platelets and haemoglobin, while CHS 828 did not seem to affect these parameters. The pharmacokinetics of 5-FU and EPI were in accordance with previously established pharmacokinetic models. The pharmacokinetics of CP and CHS 828 were both described by one-compartment models. CONCLUSIONS: This study illustrates the possibility of measuring antitumour effect, haematological toxicity and pharmacokinetics in the same animal using the hollow-fibre model.

Animals↗
PubMed2000

Chemosensory control of pollen ingestion in the hoverfly Eristalis tenax by labellar taste hairs.

The labellar gustatory system of the dronefly Eristalis tenax L. (Syrphidae; Diptera) that enables the fly to discriminate between pollen and nectar is investigated, and the triggering of pollen ingestion is examined. In behavioural preference tests, exhaustively extracted pollen of the sunflower Helianthus annuus is consumed in smaller amounts than untreated pollen, indicating that water-soluble substances are important for acceptance. Dry pollen is preferred over moist pollen in which the grains stick together, suggesting that mechanical properties of the pollen also play a role in its sensory assessment. Electrophysiological studies of the labellar taste hairs reveal that aqueous extracts of pollen (2% w/v) stimulate the salt receptor cell, but not the sugar receptor cell. The response of the water receptor cell remains the same as to pure water (or standard electrolyte, 10 mmol.l-1 KCl). Of the 20 amino acids tested, the salt cell is sensitive only to proline in a submillimolar range. Behavioural experiments support the electrophysiological findings. When KCl is applied at concentrations eliciting salt-cell spike frequencies equal to those produced by pollen extract (which is often accepted), the water receptor cell is inhibited and a pronounced rejection behaviour occurs. This rejection of concentrated salt solution in Eristalis is therefore mainly mediated by the inhibition of the water cell.

Action Potentials↗
PubMed2000

The unpredictable character of congenital cystic lung lesions.

BACKGROUND: The spectrum of congenital cystic disease of the lung ranges from hydrops and neonatal respiratory distress to asymptomatic lesions. Surgical management is dictated by the presence of symptoms, recurrent infection, and the potential risk of malignant transformation. METHODS: Since 1995, all consecutive patients with congenital cystic lung lesions underwent follow-up for symptoms, treatment, and correlation of presumptive with pathological diagnosis. RESULTS: Twelve cystic lung lesions were identified. Seven were diagnosed with mediastinal shift in utero; in 6 of 7, the shift subsequently resolved. Overall, 6 of 7 lesions that were followed up serially decreased in size. Two patients were symptomatic in utero; 1 underwent thoracoamniotic shunting, 1 pleurocentesis for impending hydrops. Postnatally, these 2, and 2 other newborns required urgent surgery. Five of 8 asymptomatic patients had elective resection by 16 months, and 4 await operation. In 6 of the 9 surgical cases (67%), there was a discrepancy between preoperative and pathological diagnosis. There were 4 hybrid congenital cystic adenomatoid malformation (CCAM)/sequestrations. CONCLUSIONS: At least 6 of 7 congenital cystic lung lesions decreased in size regardless of gestational age or presence of mediastinal shift. Antenatal intervention is therefore rarely indicated. Hybrid morphology may necessitate resection of stable, asymptomatic lesions to prevent the theoretical concern for associated malignancies as well as other complications of CCAM.

Adult↗
PubMed2000

Class II correction in patients treated with class II elastics and with fixed functional appliances: a comparative study.

The aim of the present study was to evaluate quantitatively the skeletal and dental changes contributing to Class II corrections in subjects treated with Class II elastics (Begg technique) compared with subjects treated with fixed functional appliances (Herbst appliance). Thirty-six male patients with Class II, Division 1 malocclusions whose treatment had not included extraction were investigated. Eighteen were treated with the Begg technique, and eighteen were treated with Herbst appliance for an average period of 1.3 and 0.5 years, respectively. Lateral radiographs in habitual occlusion were taken at the start of treatment and 12 months afterwards. In the Begg group, the maxilla moved forward 1 mm more than in the Herbst group, and the mandible moved 1 mm more in the Herbst group than in the Begg group. The skeletal improvement in the Herbst group exceeded the changes in the Begg group by, on average, 2.0 mm (P <.01). The overjet reduction in the Begg group was larger (2.1 mm; P <.01) than in the Herbst group, mostly because of dental movements. The skeletal part of the overjet reduction was 4% in the Begg group compared with 51% in the Herbst group. The molar correction was similar in both groups, but in the Begg group, the skeletal improvement was 10%, compared with 66% in the Herbst group. The overbite correction and the increase in the anterior lower facial height and in the NSL/ML angle were larger in the Begg group (P <.05). The conclusions of this study were that the changes contributing to the Class II corrections in Begg and Herbst therapy were skeletal and dental. The skeletal changes were, however, larger in the Herbst-treated group. On the other hand, favorable and unfavorable vertical changes were more pronounced in the group treated with Class II elastics.

Adolescent↗
PubMed2000

The costs of HIV/AIDS care at government hospitals in Zimbabwe.

According to official figures, HIV infection in Zimbabwe stood at 700 000-1 000 000 in 1995, representing 7-10% of the population, with even higher expected numbers in 2000. Such high numbers will have far reaching effects on the economy and the health care sector. Information on costs of treatment and care of HIV/AIDS patients in health facilities is necessary in order to have an idea of the likely costs of the increasing number of HIV/AIDS patients. Therefore, the present study estimated the costs per in-patient day as well as per in-patient stay for patients in government health facilities in Zimbabwe with special emphasis on HIV/AIDS patients. Data collection and costing was done in seven hospitals representing various levels of the referral system. The costs per in-patient day and per in-patient stay were estimated through a combination of two methods: bottom-up costing methodology (through an in-patient note review) to identify the direct treatment and diagnostic costs such as medication, laboratory tests and X-rays, and the standard step-down costing methodology to capture all the remaining resources used such as hospital administration, meals, housekeeping, laundry, etc. The findings of the study indicate that hospital care for HIV/AIDS patients was considerably higher than for non-HIV/AIDS patients. In five of the seven hospitals visited, the average costs of an in-patient stay for an HIV/AIDS patient were found to be as much as twice as high as a non-HIV/AIDS patient. This difference could be attributed to higher direct costs per in-patient day (medication, laboratory tests and X-rays) as well as longer average lengths of stay in hospital for HIV/AIDS patients compared with non-infected patients. Therefore, the impact on hospital services of increasing number of HIV/AIDS patients will be enormous.

Cost Allocation↗
PubMed1999

Effect of branch frequency in Aspergillus oryzae on protein secretion and culture viscosity.

Highly branched mutants of two strains of Aspergillus oryzae (IFO4177, which produces alpha-amylase, and a transformant of IFO4177 [AMG#13], which produces heterologous glucoamylase in addition to alpha-amylase) were generated by UV or nitrous acid mutagenesis. Four mutants of the parental strain (IFO4177), which were 10 to 50% more branched than the parental strain, were studied in stirred batch culture and no differences were observed in either the amount or the rate of enzyme production. Five mutants of the transformed parental strain (AMG#13), which were 20 to 58% more branched than the parental strain, were studied in either batch, fed-batch or continuous culture. In batch culture, three of the mutants produced more glucoamylase than the transformed parental strain, although only two mutants produced more glucoamylase and alpha-amylase combined. No increase in enzyme production was observed in either chemostat or fed-batch culture. Cultures of highly branched mutants were less viscous than those of the parental and transformed parental strains. A linear relationship was found between the degree of branching (measured as hyphal growth unit length) and culture viscosity (measured as the torque exerted on the rheometer impeller) for these strains. DOT-controlled fed-batch cultures (in which the medium feed rate was determined by the DOT) were thus inoculated with either the transformed parent or highly branched mutants of the transformed parent to determine whether the reduced viscosity would improve aeration and give higher enzyme yields. The average rate of medium addition was higher for the two highly branched mutants (ca. 8.3 g medium h(-1)) than for the parental strain (5.7 g medium h(-1)). Specific enzyme production in the DOT controlled fed-batch cultures was similar for all three strains (approx. 0.24 g alpha-amylase and glucoamylase [g of biomass](-1)), but one of the highly branched mutants made more total enzyme (24.3 +/- 0.2 g alpha-amylase and glucoamylase) than the parental strain (21.7 +/- 0.4 g alpha-amylase and glucoamylase).

Antifungal Agents↗
PubMed1999

Overactivation of phospholipase C-gamma1 renders platelet-derived growth factor beta-receptor-expressing cells independent of the phosphatidylinositol 3-kinase pathway for chemotaxis.

We have previously shown that porcine aortic endothelial cells expressing the Y934F platelet-derived growth factor (PDGF) beta-receptor mutant respond to PDGF-BB in a chemotaxis assay at about 100-fold lower concentration than do wild-type PDGF beta-receptor-expressing cells (Hansen, K., Johnell, M., Siegbahn, A. , Rorsman, C., Engström, U., Wernstedt, C., Heldin, C.-H., and Rönnstrand, L. (1996) EMBO J. 15, 5299-5313). Here we show that the increased chemotaxis correlates with increased activation of phospholipase C-gamma1 (PLC-gamma1), measured as inositol-1,4, 5-trisphosphate release. By two-dimensional phosphopeptide mapping, the increase in phosphorylation of PLC-gamma1 was shown not to be selective for any site, rather a general increase in phosphorylation of PLC-gamma1 was seen. Specific inhibitors of protein kinase C, bisindolylmaleimide (GF109203X), and phosphatidylinositol 3-kinase (PI3-kinase), LY294002, did not affect the activation of PLC-gamma1. To assess whether increased activation of PLC-gamma1 is the cause of the hyperchemotactic behavior of the Y934F mutant cell line, we constructed cell lines expressing either wild-type or a catalytically compromised version of PLC-gamma1 under a tetracycline-inducible promoter. Overexpression and concomitant increased activation of wild-type PLC-gamma1 in response to PDGF-BB led to a hyperchemotactic behavior of the cells, while the catalytically compromised PLC-gamma1 mutant had no effect on PDGF-BB-induced chemotaxis. Furthermore, in cells expressing normal levels of PLC-gamma1, chemotaxis was inhibited by LY294002. In contrast, the increase in chemotactic response seen upon overexpression of PLC-gamma1 was not inhibited by the PI3-kinase inhibitor LY294002. These observations suggest the existence of two different pathways which mediate PDGF-induced chemotaxis; depending on the cellular context, the PI3-kinase pathway or the PLC-gamma1 pathway may dominate.

Amino Acid Substitution↗
PubMed1999

Dissecting functions of the retinoblastoma tumor suppressor and the related pocket proteins by integrating genetic, cell biology, and electrophoretic techniques.

The members of the 'pocket protein' family, comprising the retinoblastoma tumor suppressor (pRB) and its relatives, p107 and p130, negatively regulate cell proliferation and modulate fundamental biological processes including embryonic development, differentiation, homeostatic tissue renewal, and defense against cancer. The large, multidomain pocket proteins act by binding a plethora of cell fate-determining and growth-stimulatory proteins, the most prominent of which are the E2F/DP transcription factors. These protein-protein interactions are in turn regulated by carefully orchestrated phosphorylation events on multiple serine and threonine residues of pRB, p107, and p130, events which are carried out, at least in part, by the cyclin-dependent kinases that form the key elements of the cell cycle machinery. Here we discuss the recently obtained new insights into the diverse functions of the pRB family, and show examples of how integration of genetic, cell biology, and a range of electrophoretic approaches help to advance our understanding of the biological roles played by the pocket proteins in both normal and cancer cells.

Amino Acid Sequence↗
PubMed1999

A new measure for distress during child sexual abuse examinations: the genital examination distress scale.

OBJECTIVE: The primary aim was to develop a simple scale to quantify indices of emotional distress during the rectal-genital (anogenital) phase of a child sexual abuse examination. METHOD: A scale successfully developed to measure reactions of children to painful procedures, in particular bone marrow aspirations, was used as a model (Elliot, Jay, & Woody, 1987). This new scale was developed to have a simplified rating format, more relevant operational definitions and possibly a different set of behavioral categories. This new scale was developed using 300 children being examined for possible child sexual abuse. Intraclass correlation coefficients identified reliable items to use. Factor analysis and Cronbach alpha were employed to understand the internal structure of the scale. Paired t-tests, Pearson correlations and hierarchical regression were used to explore validity. RESULTS: A simple 7-item scale was developed along with two subscales representing agitated and verbally mediated distress. Ratings of distress were significantly greater during the anogenital phase than the general physical part of the examination. Increased distress was associated with positive physical findings. Ratings by the children that they disliked the physician looking at their bodies provided discriminant validity by correlating with increased scores for emotional distress during the anogenital segment of the examination. CONCLUSION: The Genital Examination Distress Scale (GEDS) has been developed for measuring the emotional distress of children during the anogenital component of child sexual abuse examinations. The GEDS has been provided for prudent use. Descriptive data offer a comparative standard for other programs and research.

Adolescent↗
PubMed1999

Overjet reduction and molar correction in fixed appliance treatment of class II, division 1, malocclusions: sagittal and vertical components.

The purpose of this study was to quantitatively evaluate skeletal and dental changes contributing to Class II correction in patients treated with the Begg technique. The sample consisted of 18 male subjects with Class II, division 1, malocclusions treated with fixed appliances (Begg technique, nonextraction) for an average period of 1.3 years (standard deviation, 0.24 years). Lateral radiographs in habitual occlusion taken at 6 months before the start of treatment, at the start of treatment, and 6, 12, and 18 months after the start of treatment were analyzed. During the control period, normal sagittal and vertical growth changes occurred. In the initial treatment period (0 to 6 months), the overjet reduction (6.6 mm; P <. 001) and the molar correction (2.2 mm; P <.001) were obtained mainly by dental movements. The overbite was reduced by 4.1 mm (P <.001). The NSL/ML and NL/ML angles increased by 1.5 degrees (P <.05) and 1. 4 degrees (P <.01), respectively, and the anterior lower facial height increased by 3.1 mm (P <.001). During the second period of treatment (6 to 12 months), the molar correction continued to improve, and the anterior lower facial height continued to increase. During the third period (12 to 18 months), a small relapse in overjet and overbite was noted, but the anterior lower facial height continued to increase. During the total treatment period (0 to 18 months), the overjet reduction and molar correction were 5.8 mm (P <. 001) and 3.0 mm (P <.001), respectively. Mandibular growth exceeded maxillary growth by 1.1 mm (P <.01). The overbite correction and the increase in anterior lower facial height were 3.0 mm (P <.001) and 5. 0 mm (P <.001), respectively. The NSL/ML angle increased 1.0 degrees (P <.05). The conclusions were that the changes contributing to the Class II correction were mostly dental. Vertically, the net effects of treatment were an increase in the mandibular plane angle and in lower anterior facial height.

Adolescent↗
PubMed1999

Upper trapezius muscle activity patterns during repetitive manual material handling and work with with a computer mouse.

Firstly, upper trapezius EMG activity patterns were recorded on the dominant side of 6 industrial production workers and on the side operating a computer mouse of 14 computer-aided design (CAD) operators to study differences in acute muscular response related to the repetitiveness of the exposure. The work tasks were performed with median arm movement frequencies ranging from 5 min(-1) to 13 min(-1) and were characterized by work cycle times ranging from less than 30 sec to several days. However, the static and median EMG levels and EMG gap frequencies were similar for all work tasks indicating that shoulder muscle loads may be unaffected by large variations in arm movement frequencies and work cycle times. An exposure variation analyses (EVA) showed that the EMG activity patterns recorded during production work were more repetitive than during CAD work, whereas CAD work was associated with more static muscle activity patterns, both may be associated with a risk of developing musculoskeletal symptoms. Secondly, upper trapezius EMG activity patterns recorded on the mouse side of the CAD operators were compared with those recorded on the non-mouse side to study differences in muscular responses potentially related to the risk of developing shoulder symptoms which were more prevalent on the mouse side. The number of EMG gaps on the mouse side were significantly lower than the values for the upper trapezius on the non-mouse side indicating that more continuous activity was present in the upper trapezius muscle on the mouse side and EVA analyses showed a more repetitive muscle activity pattern on the mouse side. These findings may be of importance to explain differences in the prevalence of shoulder symptoms.

Adult↗
PubMed1999

The safety and effectiveness of esmolol in the perioperative period in patients undergoing abdominal aortic surgery.

OBJECTIVES: To determine (1) if perioperative use of esmolol in major vascular surgery patients provides strict heart rate (HR) control, (2) what doses of esmolol are required to do this, and (3) does this control influence myocardial ischemia or result in adverse consequences. DESIGN: Prospective study of 40 patients randomized to two groups: The HR was controlled to either less than 80 beats/min (group 80) or less than 110 beats/min (group 110) using esmolol. Patients were monitored continuously for electrocardiographic changes perioperatively. HR control began after induction of anesthesia and continued for 48 hours thereafter. SETTING: Operating room and intensive care unit. PATIENTS: Patients undergoing abdominal vascular surgery involving aortic cross-clamping. INTERVENTIONS: Esmolol was titrated until the target HR was met. MEASUREMENTS AND RESULTS: Only one patient demonstrated an adverse effect. The median infusion rates were 100 and 12.5 microg/kg/min for groups 80 and 110. Target HR was met less in group 80 than in group 110, primarily in the postoperative period. Ischemia patterns were not significantly different between groups. CONCLUSION: Using esmolol for HR control in the intraoperative period for abdominal vascular surgery patients is effective and safe. HR control was much less effective in the postoperative period, but esmolol is safe when used at recommended doses. Further study with a larger number of patients is necessary to determine whether strict HR control with esmolol affects the incidence of myocardial ischemia or infarction in this patient population.

Adrenergic beta-Antagonists↗
PubMed1999

Methodologic aspects of acetylcholine-evoked relaxation of rabbit aorta.

The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased with time. N(G)-Nitro-L-arginine abolished the inhibitory effect of EDTA and ascorbic acid. Acetylcholine evoked a rapid concentration-dependent relaxation that recovered spontaneously and slowly, but fully, with time. Relaxation evoked by equieffective concentrations of carbachol and acetylcholine had the same time course. Cumulative addition of acetylcholine (10(-7)-3 x 10(-5) M) caused a marked relaxation that was reverted slightly at high concentrations. The relaxation was the same with rings derived from the upper, middle, and lower part of the thoracic aorta. Two consecutive concentration-response curves for acetylcholine obtained at a 2-h interval demonstrated a slight development of tachyphylaxis. The relaxation was inversely related to precontractile tension evoked by phenylephrine when expressed as a percentage, but independent when expressed as g tension. Storage of aorta in cold salt solution for 24 h did not alter the relaxation. EDTA and ascorbic acid did not alter the relaxation. It is concluded that (1) EDTA and ascorbic acid can not be used with impunity to stabilize catecholamines used as preconstriction agents; (2) the reversal of the acetylcholine-evoked relaxation is not due to hydrolysis of acetylcholine; (3) the relaxation is uniform in all segments of thoracic aorta; (4) cold storage of aorta does not alter the relaxation; and (5) acetylcholine releases the same amount of relaxing factor, irrespective of the precontractile tension.

Acetylcholine↗
PubMed1999

Risk factors for lack of recovery of ADL independence after hospital discharge.

OBJECTIVE: To determine risk factors for lack of recovery of independent functioning after hospitalization for acute medical illness. DESIGN: Secondary analysis of cohort study of patients receiving home nursing after discharge. SETTING: Evaluations performed in the home after discharge and 1 month later. PARTICIPANTS: A total of 73 adults aged 65 years and older who were independent in activities of daily living (ADLs) before hospitalization and dependent at discharge. MEASUREMENTS: Self-report and objective measures of function, mobility, and cognition. OUTCOME: Return to independence in ADLs 1 month after discharge. RESULTS: Fifty-nine percent of patients did not return to previous ADL independence by 1 month postdischarge. The likelihood for not recovering was 87% (95% CI, 70-100%) if a patient had a Mini-Mental State Examination score (MMSE) < 24 at discharge (P = .015). Among patients with good cognition, 85% (95% CI, 66-100%) of those who used an assistive device indoors before hospitalization did not recover (P = .007). Among patients with good cognition and no previous assistive device use, 73% (95% CI, 47-99%) of those with a Timed "Up and Go" of > or = 40 seconds did not recover (P = .012). The likelihood of recovery was high (76%, 95% CI 56-96%) if a patient had no assistive device prehospital, a good MMSE, and a Timed "Up and Go" of < 20 seconds. CONCLUSION: We hypothesize that a classification strategy using cognition, prehospital mobility, and discharge physical performance will predict patients who are less likely to recover functional independence after hospitalization. If this is validated in future study, it may help clinicians identify patients who are more likely to benefit from additional intervention.

Activities of Daily Living↗
PubMed1999

Flavin-containing monooxygenase-mediated N-oxidation of the M(1)-muscarinic agonist xanomeline.

The involvement of flavin-containing monooxygenases (FMOs) in the formation of xanomeline N-oxide was examined in various human and rat tissues. Expressed FMOs formed xanomeline N-oxide at a significantly greater rate than did expressed cytochromes P-450. Consistent with the involvement of FMO in the formation of xanomeline N-oxide in human liver, human kidney, rat liver, and rat kidney microsomes, this biotransformation was sensitive to heat treatment, increased at pH 8.3, and inhibited by methimazole. The latter two characteristics were effected to a lesser extent in human kidney, rat liver, and rat kidney microsomes than were observed in human liver microsomes, suggesting the involvement of a different FMO family member in this reaction in these tissues. As additional proof of the involvement of FMO in the formation of xanomeline N-oxide, the formation of this metabolite by a characterized human liver microsomal bank correlated with FMO activity. The FMO forming xanomeline N-oxide by human kidney microsomes exhibited a 20-fold lower K(M) (average K(M) = 5.5 microM) than that observed by the FMO present in human liver microsomes (average K(M) of 107 microM). The involvement of an FMO in the formation of xanomeline N-oxide in rat lung could not be unequivocally demonstrated. These data and those in the literature suggest that the increased prevalence of N-oxidized metabolites of xanomeline after s.c. dosing as compared with oral dosing may be due to differences in the affinity of various FMO family members for xanomeline or to differences in exposure to xanomeline that these enzymes receive under different dosing regimens.

Animals↗