Norwegian general population normative data for the European Organization for Research and Treatment of Cancer questionnaires: the Quality of Life Questionnaire-Core 30, the Sexual Health Questionnaire QLQ-SHQ22 and the sexual domains of the QLQ-BR23/BR45.

OBJECTIVE: The aim of this study was to provide sex-, age-, and morbidity-specific Norwegian general population normative values for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires QLQ-C30, the sexual health questionnaire QLQ-SHQ22 and the sexual domains of the breast modules QLQ-BR23 and QLQ-BR45. METHODS: A random nationwide sample stratified by sex and age groups (18-29, 30-39, 40-49, 50-59, 60-69 and ≥70 years) was drawn from the Norwegian National Population Register. Participants were notified through national online health services (HelseNorge) and postal mail. The survey included sociodemographic background information, health-related quality of life assessed by the EORTC questionnaires, and morbidity assessed by the Self-Administered Comorbidity Questionnaire. Multivariable linear regression was carried out to estimate the associations of age, sex and morbidity with the EORTC scale and item scores. RESULTS: Of the 15,627 eligible individuals, 5135 (33%) responded. Women and persons with morbidities reported lower functioning and higher symptom burden than men and persons without morbidities, respectively, on nearly all EORTC scales. Sex differences were most prominent for emotional functioning, pain, fatigue and insomnia (QLQ-C30), body image, sexual functioning (QLQ-BR23/45), importance of sexual activity, libido and fatigue (QLQ-SHQ22). The score differences between persons with and without morbidity were highly significant and largest in the youngest and middle-aged groups. CONCLUSION: This is the first study to provide normative values for the EORTC sexual health questionnaire QLQ-SHQ22 and the sexual subscales of the QLQ-BR23 and QLQ-BR45 for all, separately in age groups by sex and morbidity.

Health-related quality of life in patients with advanced melanoma treated with ipilimumab: prognostic implications and changes during treatment.

BACKGROUND: We have previously reported that the safety and efficacy of ipilimumab in real-world patients with metastatic melanoma were comparable to clinical trials. Few studies have explored health-related quality of life (HRQL) in real-world populations receiving checkpoint inhibitors. This study reports HRQL in real-world patients receiving ipilimumab and assesses the prognostic value of patient-reported outcome measures. PATIENTS AND METHODS: Ipi4 (NCT02068196) was a prospective, multicentre, interventional phase IV trial. Real-world patients (N = 151) with metastatic melanoma were treated with ipilimumab 3 mg/kg intravenously as labelled. HRQL was assessed by the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire at baseline and after 10-12 weeks. RESULTS: The European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire was completed by 93% (141/151 patients) at baseline, and by 82% at 10-12 weeks. Poor performance status and elevated C-reactive protein (CRP) were associated with worse baseline HRQL. Clinically relevant and statistically significant deteriorations in HRQL from baseline to weeks 10-12 were reported (P <0.05). Baseline physical functioning [hazard ratio (HR) 1.96, P = 0.016], role functioning (HR 2.15, P <0.001), fatigue (HR 1.60, P = 0.030), and appetite loss (HR 1.76, P = 0.012) were associated with poorer overall survival independent of performance status, lactate dehydrogenase (LDH), and CRP. We further developed a prognostic model, combining HRQL outcomes with performance status, LDH, and CRP. This model identified three groups with large and statistically significant differences in survival. CONCLUSIONS: Systemic inflammation is associated with impaired HRQL. During treatment with ipilimumab, HRQL deteriorated significantly. Combining HRQL outcomes with objective risk factors provided additional prognostic information that may aid clinical decision making.

Oxygen consumption in T-47D cells immobilized in alginate.

OBJECTIVES: Encapsulation or entrapment of cells is increasingly being used in a wide variety of scientific studies for tissue engineering and development of novel medical devices. The effect on cell metabolism of such systems is, in general, not well characterized. In this work, a simple system for monitoring respiration of cells embedded in 3-D alginate cultures was characterized. MATERIALS AND METHODS: T-47D cells were cultured in alginate gels. Oxygen concentration curves were recorded within cell-gel constructs using two different sensor systems, and cell viability and metabolic state were characterized using confocal microscopy and commercially available stains. RESULTS: At sufficient depth within constructs, recorded oxygen concentration curves were not significantly influenced by influx of oxygen through cell-gel layers and oxygen consumption rate could be calculated simply by dividing oxygen loss in the system per time, by the number of cells. This conclusion was supported by a 3-D numeric simulation. For the T-47D cells, the oxygen consumption rate was found to be 61 ± 6 fmol/cell/h, 3-4 times less than has previously been found for these cells, when grown exponentially in monolayer culture. CONCLUSIONS: The experimental set-up presented here may be varied in multiple ways by changing the cell-gel construct 3-D microenvironment, easily allowing investigation of a variety of factors on cell respiration.

Does the cylinder model of gastric evacuation predict observed evacuation of mixed meals of prey of contrasting geometries in a piscivorous fish?

The simple surface abstraction of the cylinder model (each prey as well as the total stomach contents is considered a cylinder that is gradually reduced by successive peeling off its curved side) was challenged by data on evacuation of a meal composed of three sandeels Ammodytes tobianus and a dab Limanda limanda fed to Atlantic cod Gadus morhua. While the body shape of A. tobianus comes close to that of a cylinder, the flatfish L. limanda takes a discoid form. As opposed to a modified form of the cylinder model, where the contrasting geometries of the fish prey were implemented, the simple, original cylinder model held the potential to predict evacuation of the individual prey types as well as the total stomach contents. Thus, the present study adds significantly to the increasing evidence that points to the generic nature of the model and its implicit square root function. Also, the present study corroborated a basic assumption that the variability of evacuation data not accounted for by the cylinder model primarily can be ascribed to the intraspecific variation in gastric performance of the predator.

Improved visualization of artificial pulmonary nodules with a new subvolume rendering technique.

BACKGROUND: The detection of small nodules in pulmonary multidetector computed tomography (MDCT) data sets is challenging, and there is a need for visualization techniques that can improve reader sensitivity and efficiency. We have developed a subvolume rendering technique ("Softslice") with nonlinear, symmetrical modulation of the relative signal intensity along the viewing direction. Our hypothesis was that this technique might provide an advantageous visual differentiation between nodules and overlapping vessels in pulmonary MDCT subvolumes. PURPOSE: To compare the Softslice subvolume rendering technique and maximum intensity projection (MIP) rendering for visualization of artificial pulmonary nodules in MDCT data sets. MATERIAL AND METHODS: Virtual, artificial pulmonary nodules were created with custom-made software. The nodules had the same signal intensity as pulmonary vessels. Approximately 50 nodules with diameter 2-7 mm were inserted in the Digital Imaging and Communications in Medicine (DICOM) image files of pulmonary MDCT data sets obtained without intravenous contrast. Each data set contained approximately 300 slices with 1-mm slice spacing. Four types of subvolumes were rendered: MIP with 10- and 20-mm subvolume thickness, and Softslice with 20- and 30-mm subvolume thickness. Three radiologists performed readings with free scrolling using 1-, 4- or 8-mm increments between subvolume positions. RESULTS: No significant differences in the number of detected nodules were found between the different renderings with free scrolling using 1- and 4-mm increments. When 8-mm increment was used, nodule detection with the 30-mm Softslice rendering was significantly superior to the other renderings (P = 0.012 vs. MIP 10 mm, P = 0.018 vs. MIP 20 mm, P = 0.021 vs. Softslice 20 mm). When the subvolume increments were changed from 4 mm to 8 mm, the most marked reduction in the number of detected nodules was seen for MIP subvolumes with 10-mm thickness (P = 0.018). CONCLUSION: The Softslice rendering technique is promising for the detection of pulmonary nodules in MDCT data sets, and may allow more efficient reading than the standard MIP subvolume technique. With 10-mm MIP rendering, the detection rate for small pulmonary nodules substantially influenced by the incremental distance between subvolumes positions.

Effect of charge and size of diffusing probe on the diffusion through calcium alginate gel matrices.

The diffusion of latex particles and low molecular weight fluorescein analogues in homogenous, well-defined calcium alginate gel matrices was studied. The experimental results indicate that the different types of diffusion probes are retarded by different mechanisms in the gel. The positively charged low molecular weight substance experienced some degree of retardation by the gels, but the diffusion rate of the uncharged low molecular weight substance was little influenced by gel composition. A wide range of diffusion rates was observed for the particles in the various gel compositions.

Preparation of a radionuclide/gel formulation for localised radiotherapy to a wide range of organs and tissues.

Localised radiotherapy by instillation of radiolabeled particles is being used to treat rheumatoid arthritis and certain tumors. Such therapy is limited to organs and tissues capable of retaining the radioactive compound until the radioactivity is sufficiently low, and the leakage to other parts of the body is no longer unacceptable. In this study, radiolabeled particles, i.e. 90Y-silica colloid particles, were encapsulated in calcium alginate gels, and the leakage of radioactivity from the gels was monitored. The purpose of the study was to develop a formulation suitable for the localised delivery of radiation therapy to a wide range of organs and tissues. An injectable gel formulation was developed, liberating only small amounts of radioactivity into the surrounding medium. The formulation is a viscous liquid at room temperature and forms a gel on heating to normal body temperature. Thus, it should be suitable for the localised delivery of radiolabeled particles to a wide range of organs and tissues. The study also includes a formulation exhibiting time-dependent gelation. However, this formulation was not found to be suitable for the purpose.

Measurement of diffusion through calcium alginate gel matrices.

The diffusion of high molecular weight dextran samples and low molecular weight quinine sulphate in homogenous calcium alginate gel matrices was studied. An experimental design suitable for studying the diffusion of substances from or through a gel sample was established. The experimental results indicate that the different types of molecules diffuse in the gel by different mechanisms. The diffusion rate of the molecules in the gel is dependent on gel composition.

Nasal administration of carbamazepine using chitosan microspheres: in vitro/in vivo studies.

The nasal route is used both for local therapies and, more recently, for the systemic administration of drugs, as well as for the delivery of peptides and vaccines. In this study the nasal administration of Carbamazepine (CBZ) has been studied using microspheres constituted by chitosan hydrochloride (CH) or chitosan glutamate (CG). Blank microspheres were also prepared as a comparison. The microspheres were produced using a spray-drying technique and characterized in terms of morphology (scanning electron microscopy, SEM), drug content, particle size (laser diffraction method) and thermal behaviour (differential scanning calorimetry, DSC). In vitro drug release studies were performed in phosphate buffer (pH 7.0). In vivo tests were carried out in sheep using the microparticles containing chitosan glutamate, chosen on the basis of the results of in vitro studies. The results were compared to those obtained after the nasal administration of CBZ (raw material) alone. For the evaluation of in vivo data statistical analysis was carried out using the unpaired t-test. Spray-drying was a good technique of preparation of CBZ-loaded microspheres. The loading of the drug into the polymeric network always led to an increase in the dissolution rate compared to CBZ raw material. The microspheres obtained using chitosan glutamate had the best behaviour both in vitro and in vivo. They increased the drug concentration in the serum when compared to the nasal administration of the pure drug (Cmax 800 and 25 ng/ml for microspheres and pure drug, respectively). The results obtained indicate that the loading of CBZ in chitosan glutamate microspheres increases the amount of the drug absorbed through the nose.

[Curettage or not after spontaneous abortion?]. / Utskrapning eller ikke etter spontanabort?

BACKGROUND: In most cases of miscarriage, standard procedure has until recently been surgical revision of the uterine cavity. MATERIAL AND METHODS: 94 women with first trimester miscarriage were randomized to surgical revision (n = 48) or expectation (n = 46) after informed consent. Women with unacceptable pain or bleeding, or uterine contents of more than 20 mm diameter on sonography were not included. The patients were followed up seven to ten days later with gynaecological examination, sonography, and determination of levels of haemoglobin, leukocytes, C-reactive protein and HCG. RESULTS: In the revision group there were no operative complications, no cases of infection, and no unscheduled consultations. Mean duration of bleeding was 4.8 days (range 1-11 days). In the observation group there were no cases of infection, surgical revision was carried out in seven patients, and there were six unscheduled consultations. Mean duration of bleeding was 7.3 days (range 2-27 days). The women undergoing surgical revision had less pain and bleeding. INTERPRETATION: Women with first trimester miscarriage may safely be observed without surgical revision but may have somewhat more pain and more vaginal bleeding than if revision is carried out.

Toxicity of gamma irradiated liposomes. 1. In vitro interactions with blood components.

Gamma irradiation is a potential technique for sterilisation of liposome suspensions. Unfortunately, gamma irradiation may result in chemical degradation of the phospholipids and the toxicological aspects have to be considered. The effects of liposome composition and gamma irradiation on the interactions of the liposomes with the hemostatic mechanisms (hemolysis, aggregation and coagulation) were studied. Non-irradiated liposome suspensions showed no hemolysis of erythrocytes. After irradiation, up to 3.1% hemolysis was measured. Least hemolysis was observed with irradiated liposomes composed of unsaturated or charged phospholipids. The negatively charged DSPG-liposomes (both non-irradiated and irradiated) induced aggregation of platelets as observed by the spectrophotometric method. However, no aggregates were seen in the microscope or measured by the aggregometer. Negatively charged liposomes also affected the coagulation cascade where prolonged coagulation times were measured. Irradiation of the liposome suspensions resulted in even longer coagulation times. The prolonged coagulation times correlated to some extent with the measured binding and depletion of calcium from plasma by the negatively charged liposomes.

Toxicity of gamma irradiated liposomes. 2. In vitro effects on cells in culture.

In this study, the effects of liposome composition and gamma irradiation on their interactions with cell cultures were studied. The cytotoxicity test and the growth inhibition test clearly revealed toxic effects of liposomes composed of unsaturated phospholipids and gamma irradiation of these preparations enhanced their toxic effects. The murine fibroblast cell-line L 929 was less affected compared to the macrophage cell-line RAW 264 with a higher endocytic capacity. On the other hand, both gamma irradiated and non-irradiated liposomes composed of saturated phospholipids were non-toxic for the cells and irradiation did not affect their drug delivery properties. Hence, it seems that gamma irradiation is appropriate for sterilisation of these liposomes.

Characterization of rheological and mucoadhesive properties of three grades of chitosan hydrochloride.

In the present study the rheological and mucoadhesive properties of three viscosity grades of a cationic polymer, chitosan, were investigated to assess the suitability of this polymer for gastroadhesive formulations. The influence of the pH, ionic strength and temperature of the hydration medium on the rheological properties was studied. The mucoadhesive performance was assessed in vitro by means of rheological synergism and tensile stress testing. A correlation was found between rheological synergism and tensile parameters (force of detachment and work of adhesion), which proves that both methods can correctly predict the mucoadhesive performance of the polymers examined. It was found that the interaction of chitosan with mucin decreases on increasing molecular weight.

Zeta potentials of human enamel and hydroxyapatite as measured by the Coulter DELSA 440.

The zeta potential of human enamel is of physiological importance for interactions between enamel surfaces and the surrounding aqueous medium of saliva. The zeta potentials of both enamel and hydroxyapatite (HA) have been examined previously by various techniques. In this study, we examined the zeta potential of human enamel and HA using the Coulter DELSA 440, which, by a laser, makes independent Doppler shift measurements of moving particles in an electric field at 4 different angles, providing advantages over previous techniques. The enamel and HA particles were suspended directly in different phosphate buffers, or first incubated for 2 hrs in parotid (PS) or whole saliva (HWS) and then suspended in the same buffers. The enamel and HA particles exhibited an overall net surface potential of -15 to -30 mV, depending on the buffer content. Incubation in PS and HWS gave less negative potentials of -8 to -14 mV. In our previous studies, the salivary micelle-like structures (SMSs), seen in TEM of parotid saliva, were observed to have a zeta potential of -9 mV (Rykke et al., 1996). The zeta potential determinations in this study support the concept of an adsorption of mostly SMSs to the enamel surfaces, with a change of the zeta potential of the enamel and HA toward that of the SMSs.

Electrical methods for skin moisture assessment.

Skin sites on 8 test subjects were treated with moisturizers, and different electrical measuring methods were compared regarding their quality in the assessment of the induced changes in the stratum corneum hydration level. Low frequency susceptance measurements were found preferable to high frequency admittance measurements, and the advantages of monopolar measurements with the three-electrode system are described.

Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally.

The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then decreased to its initial value within 12 h in all but one subject; the half-life was 96 min. Thiamin mono and -diphosphate increased moderately (56%), and decreased slowly; the half-life of diphosphate was 664 min. Within 24 h, 53% of the administered dose was recovered in the urine, indicating a restricted distribution. After oral administration, the peak thiamin concentration in plasma was reached after 53 min and the concentration then had increased to 179% of its initial value. The elimination half-life was 154 min, and only 2.5% of the given dose was recovered in the urine. The relative bioavailability of thiamin was 5.3%. A moderate amount of the administered thiamin was stored in blood. Other body tissues must play an important part, therefore, in the distribution of thiamin.

Biologic monitoring of chromium and nickel among stainless steel welders using the manual mental arc method.

Forty manual metal arc welders welding stainless steel (SS) were monitored for 1-7 workdays measuring total chromium (Cr), water-soluble hexavalent CrVI, and nickel (Ni) in the working atmosphere, and Cr and Ni in blood and urine. The mean daily increase was 1.0 microgram Cr/l in plasma and 5.6 micrograms Cr/g creatinine in urine. There were significant correlations between total Cr and CrVI in air and the total Cr in biologic fluids. This was not the case for the corresponding correlations for Ni. The observed correlations between urinary and plasma Cr levels may permit interchange of these body fluids for biologic monitoring at high exposures. The results indicate that urine sampled after work is a body fluid versatile for routine monitoring of Cr in SS welders. Smokers had higher levels of Cr in biologic fluids than did nonsmokers at equivalent levels of air CrVI. The results also indicate that filter masks provide better protection against uptake of Cr in the airways than air-stream helmets.

Chemical composition and morphology of welding fume particles and grinding dusts.

Elemental composition and morphology of pure manual metal arc (MMA) welding fumes, pure grinding dust, and combined fume/dust air samples were collected and determined separately under semilaboratory conditions. The base material was stainless steel. The purpose of the present study was to create a "synthetic" work situation under semilaboratory conditions by combining one grinding period and two MMA welding periods and comparing these results with results during welding in a workshop. The duty cycles of pure welding and of pure grinding were also observed. A comparison was also made between metal inert gas (MIG) and MMA welding on stainless steel as well as a nickel-rich alloy under regular conditions. The amount of collected material was determined by weighing the membrane filters before and after exposure, and the element contents were determined by atomic spectroscopy. Other transmission electron microscopy (TEM) filters were used for TEM and computer-image analysis, in which the amount of collected material and its morphological characteristics were observed. The arcing time and the consumption of filler material were estimated for different kinds of electrodes. Chemical analysis showed that the contents of manganese and total chromium were lower in grinding dust than in welding fumes. The contents of hexavalent chromium, Cr(VI), in grinding dust were undetectable. Samples collected in welding shops where concomitant grinding was performed contained about 30% less Cr(VI) than those collected under laboratory conditions during welding only. The sizes and shapes of the particles depend on the welding process and distance of collection from the plume of the fume. To compare laboratory experiments with regular welding situations, the experiment must resemble industrial welding.(ABSTRACT TRUNCATED AT 250 WORDS)