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Biomedical subjects

H Andersson

Publications and source records attributed to H Andersson.

At least 37 records · Page 2Linked to original sources

Prescribing, prescription costs and adherence to formulary committee recommendations: long-term differences between physicians in public and private care.

BACKGROUND: In southern Sweden, many general practitioners (GPs) participate in an extensive postgraduate drug education programme, and many health centres are also fed back crude local drug statistics from pharmacists in the area. Private physicians and hospital physicians have not participated in these programmes. OBJECTIVE: The drug prescribing habits and costs of GPs, hospital physicians and private physicians were compared. METHODS: Each March, from 1990 to 1997, all prescriptions dispensed at the eight pharmacies in Växjö, a city and municipality in southern Sweden, were registered, specifying drug(s) prescribed, price, patient's age, sex and area of residence, and prescriber's place of work and category. RESULTS: Overall, the costs of prescribed drugs increased with time, even in 1997 when the prescribing volume was reduced due to changes in the reimbursement system. The cost increase was caused by increased prescribing of newer, more expensive drug alternatives. However, within each of the eleven major drug groups, the drugs prescribed by GPs were less expensive than those prescribed by hospital physicians and, particularly, private physicians. Moreover, even though GPs prescribed more and a wider range of drugs, they also had a higher degree of adherence to the recommendations by the formulary committee. CONCLUSION: GPs prescribed less expensive drugs and had a higher degree of adherence to the recommendations by the formulary committee than other categories of physicians. One reason for these differences may be that the GPs participated in regional and local educational activities aimed at the rationalisation of drug prescribing.

Drug Prescriptions↗

High-efficiency astatination of antibodies using N-iodosuccinimide as the oxidising agent in labelling of N-succinimidyl 3-(trimethylstannyl)benzoate.

Monoclonal antibodies C215, reactive with colorectal carcinomas, and MOv18, reactive with most of the ovarian carcinomas, were radiohalogenated with [211At]astatine. The radiohalogen was conjugate coupled to antibodies via the intermediate labelling reagent N-succinimidyl-3-(trimethylstannyl)benzoate (m-MeATE) in a two-step, single-pot reaction. Optimisation of the labelling of the reagent was achieved using N-iodosuccinimide, NIS, as the oxidising agent. The yields ranged from 69-95% in the labelling of 0.1-1.0 nmole of the m-MeATE precursor. Subsequent conjugation to antibodies resulted in yields of 58+/-7%. In vitro binding to tumour cells showed that the immunoreactivity of both antibodies was retained after astatine labelling.

Antibodies, Monoclonal↗

Seasonal alterations in circadian melatonin rhythms of the European wild boar and domestic gilt.

The aims of the present study were: 1) to determine if the European wild boar exhibits a circadian pattern of melatonin secretion under its natural light environment; 2) to compare this pattern with the pattern in domestic pigs reared under the light environment typical for domesticity; and 3) to determine if there are seasonal alterations in melatonin rhythms. Four to six young, pure-bred, European wild boars and four to six cross-bred (Yorkshire x Finnish Landrace) domestic gilts were sampled at 2-hr intervals for 48 hr at the spring/autumn equinoxes and summer/winter solstices. Samples were obtained via saphenous arterial catheters from the wild boars and via ear vein catheters from the domestic gilts. The ambient light intensity was recorded simultaneously with sampling both outdoors and indoors. Following ether extraction, the serum samples were assayed for melatonin using a commercial RIA (Bühlman). All the experimental animals exhibited a distinct circadian pattern in melatonin secretion, with high concentrations occurring during the scotophase. There was no difference in scotophase melatonin response between the wild boars and domestic gilts in any season in terms of mean melatonin concentration or peak value. The mean duration of increased melatonin secretion (more than two standard deviations over a mean photophase concentration) in 24 hr in the wild boars in spring, summer, autumn and winter, was 10, 6, 11 and 17 hr, respectively, and in the domestic gilts, 9, 8, 12 and 11 hr, respectively. These results demonstrate the existence of circadian rhythm in melatonin secretion in both the European wild boar and domestic pig. In both groups, the duration of secretion is subject to seasonal alterations. The results suggest no difference in photoperiodic-melatonin transduction between the European wild boar and domestic pig whether due to altered genotype or reduced light environment.

Animals↗

Water-miscible tocopherol is not superior to fat-soluble preparation for vitamin E absorption in cystic fibrosis.

UNLABELLED: Vitamin E deficiency is a major problem in cystic fibrosis. Modern pancreatic enzymes may improve the absorption of fat-soluble vitamins to make water dispersion less important. In order to compare the absorption of fat-soluble (F) and water-miscible (W) tocopheryl acetate, equivalent amounts (10 mg/kg body weight) were given to five patients with cystic fibrosis (CF) and five age- and sex-matched healthy controls. Serum was analysed for vitamin E using HPLC before and 1, 2, 3, 4, 6, 8, 10, 24 and 28 h after the oral intake. The median peak concentrations in the sera of controls were 41.9 micromol/L after F and 39.8 micromol/L after W preparations, corresponding values in CF patients being 21.3 and 26.8 micromol/L, and corresponding means +/- SD were 41.6+/-6.7 and 38.4+/-3.3, and 27.1+/-14.5 and 28.8+/-8.3, respectively. Although the area under the curve was lower for W than F preparations in both CF patients and controls, these differences were not significant. CONCLUSION: The results in our study are consistent with those of an earlier study using the same preparation and suggest that it is not necessary to use water-miscible preparation of alpha-tocopheryl acetate in CF patients receiving modern pancreatic enzyme supplementation.

Absorption↗

Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study.

BACKGROUND: The ketohexose D-tagatose is a new sweetener with a low energy content. This low energy content may be due to either low absorption of the D-tagatose or decreased absorption of other nutrients. OBJECTIVE: The aims of this study were to measure the excretion of D-tagatose from the human small bowel, to calculate the apparent absorption of D-tagatose, and to study the effects of D-tagatose on the small-bowel excretion of other carbohydrates. DESIGN: A controlled diet was served for 2 periods of 2 d during 3 consecutive weeks to 6 ileostomy subjects. In one of the periods, 15 g D-tagatose was added to the diet daily. Duplicate portions of the diet and ileostomy effluents were freeze-dried and analyzed to calculate the apparent net absorption of D-tagatose and carbohydrates. RESULTS: Median D-tagatose excretion was 19% (range: 12-31%), which corresponded to a calculated apparent absorption of 81% (69-88%). Of the total amount of D-tagatose excreted [2.8 g (1.7-4.4 g)], 60% (8-88%) was excreted within 3 h. Between 3 and 5 h, 32% (11-82%) was excreted. Excretion of wet matter increased by 41% (24-52%) with D-tagatose ingestion. Sucrose and D-glucose excretion increased to a small extent, whereas no significant changes were found in the excretion of dry matter, energy, starch, or D-fructose. CONCLUSIONS: The apparent absorption of 15 g D-tagatose/d was 81%. D-Tagatose had only a minor influence on the apparent absorption of other nutrients.

Adult↗

Plasma melatonin levels in relation to the light-dark cycle and parental background in domestic pigs.

To study porcine melatonin secretion in a stable environment 3 daytime (10.00-15.00) and 3 nighttime (22.00-03.00) plasma samples were collected by jugular venipuncture from 15 gilts, 16 sows, 3 boars and 48 piglets (24 females and 24 males from 8 litters) and analysed for melatonin content. Nighttime melatonin concentrations were higher than daytime melatonin concentrations (p < 0.001), whereas no effect of sampling order could be discerned. The 3 adult Hampshire boars had higher melatonin concentrations during the day and the night, than the 31 adult Yorkshire females (p < 0.05). There was no clear difference between gilts and sows in plasma melatonin. The gilts from one of the litters had higher plasma melatonin concentrations than the gilts in 3 other litters (p < 0.05). Among the 48 piglets, the increase of nocturnal melatonin secretion differed between litters (p < 0.01), whereas the influence of father was not quite significant (p = 0.12). No difference in daytime melatonin concentrations between litters could be found, and there was no difference in melatonin levels between the male and female piglets. In conclusion, this study demonstrates that domestic pigs express a nocturnal increase of melatonin secretion in a standard stable environment. For some animals the amplitude of nighttime melatonin secretion was very low, although always higher than the daytime base levels. Furthermore, the levels of nighttime melatonin secretion differed between litters, which suggests a genetic background.

Animals↗

In vitro model for frontal sinus obliteration with bioactive glass S53P4.

An in vitro model was used to investigate the behavior of a massive frontal sinus obliteration with bioactive glass S53P4 (BG) for clinical purposes. Two sizes of granules (0.63-0.8 mm or 0.8-1.0 mm) in 16 separate BG amounts, weight 25 g, were tested both in simulated body fluid (SBF) and a buffer containing trishydroxymethyl aminomethane citric acid (TRIS-c.a) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct current plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG masses were scanned by computer tomography (CT) and the scans analyzed by Region of Interest (ROI) technique. Calcium phosphate (CaP)- and silica (Si)-gel-layers were studied by scanning electron microscopy (SEM) at 1, 3, and 6 months. Cumulative loss of Si and P was stronger in TRIS -c.a than in SBF (p < 0.0001), and it was higher with smaller than with larger granules in both solutions (p < 0.0001). This was shown correspondingly by the decrease in Hounsfield units (HU) by ROI analysis (p < 0.0001). In SBF-soaked BG masses, the CaP-layer occurred on the uppermost granules, and in TRIS-c.a at 3-6 months, on the granules in the center and lower parts. The decrease of HU seems to reveal indirectly the resorption of BG.

Body Fluids↗

Influence of light environment and photoperiod on plasma melatonin and cortisol profiles in young domestic boars, comparing two commercial melatonin assays.

Eighteen crossbred boars, three siblings from each of six litters, were distributed randomly among three groups after weaning. The 'Natural long-day' group was housed in a standard room with windows, whereas the 'Artificial long-day' and 'Artificial short-day' groups were housed in light-sealed rooms and under an artificial light regimen (1400 lx). In spring (16-17 hr of light) plasma levels of melatonin and cortisol were measured in samples collected hourly for 24 hr. Two commercial melatonin radioimmunoassays with preassay diethyl ether extraction were compared. Only the assay from Bühlmann Laboratories AG showed low to undetectable melatonin levels during the light-phase and was used for further analysis. Dark-phase melatonin concentrations were higher than light-phase melatonin concentrations (P < 0.001). Dark-phase melatonin concentrations were higher in the 'Natural long-day' group than in the 'Artificial long-day' and the 'Artificial short-day' groups (P < 0.001). Sire had a significant effect on dark-phase melatonin concentrations (P < 0.01), but not on light-phase levels. Cortisol concentrations were higher during the light-phase than during the dark phase, and light-phase cortisol concentrations were higher in the 'Natural long-day' group than in the 'Artificial long-day' and the 'Artificial short-day' groups (P < 0.01). This study showed that peripubertal boars express a typical circadian melatonin rhythm under both artificial light regimens and in standard pig stable environment. Natural photoperiod and indoor lighting seem to interact in shaping the melatonin profile in standard stable environment. The great individual variation in the amplitude of the dark-phase melatonin levels could in this study be explained by the different sires.

Animals↗

Will recommended changes in fat and fibre intake affect cholesterol absorption and sterol excretion? An ileostomy study.

OBJECTIVE: To study cholesterol absorption and excretion in ileostomy subjects with different intakes of saturated fat and dietary fibre. DESIGN: Short-term experimental study, with four controlled diets in repeated measurements. SETTING: Out-patients at metabolic-ward kitchen. SUBJECTS: Nine healthy volunteers with conventional ileostomy after colectomy because of ulcerative colitis. INTERVENTIONS: Four diet periods, each of 3 days duration: high saturated fat and low dietary fibre (STAND); reduced saturated fat (RESAT); high saturated fat and high fibre (FATFIB); and reduced saturated fat and high fibre (RESATFIB). MAIN OUTCOME MEASURES: Absorption of cholesterol, and ileal excretion of cholesterol, bile acids, fat and energy. Differences between diets evaluated with Friedman's two-way analysis of variance by rank sum with Bonferroni adjustment, and post hoc differences assessed by rank sum comparison. RESULTS: RESAT and RESATFIB reduced fractional cholesterol absorption by 7% and 10%; RESATFIB and FATFIB increased net cholesterol excretion by 46% and 54% respectively. Further, RESATFIB increased net sterol excretion by 18%, all compared to STAND (P<0.05 for all). All three intervention diets contained more phytosterols than STAND (P<0.05), and the phytosterol content was inversely correlated to fractional cholesterol absorption (r=-0.77, P<0.01). CONCLUSIONS: Current nutrition recommendations to reduce saturated fat and increase dietary fibre affect sterol excretion additively. The effect on cholesterol absorption might be partly explained by the content of dietary plant sterols. SPONSORSHIP: Supported by grants from the Gothenburg Medical Society, grant numbers 94/086 and 99/082, and by the University of Gothenburg.

Adult↗

The curative and palliative potential of the monoclonal antibody MOv18 labelled with 211At in nude mice with intraperitoneally growing ovarian cancer xenografts--a long-term study.

The purpose of the present study was to investigate the therapeutic efficacy of 211At-labelled specific monoclonal antibody MOv18 in nude mice with intraperitoneal growth of the human ovarian cancer cell line OVCAR3. In the first part of the study the antibody was injected intraperitoneally when the cancer growth was microscopic. The injected activity was 485-555 kBq. The median survival for treated mice was 213 days compared to 138 days for untreated mice (p < 0.014, log-rank test). No obvious toxicity was seen. Thirty-three percent of the mice were apparently free of cancer after 7 months and were probably cured. In the second part of the study mice with macroscopic cancer and signs of ascites were injected intraperitoneally with the same 211At-labelled antibody (377-389 kBq). This treatment possibly delayed the production of ascites. Hopefully radioimmunotherapy with regionally administered 211At-labelled antibody will be of value in women with ovarian cancer as well.

Animals↗

Soy sterol esters and beta-sitostanol ester as inhibitors of cholesterol absorption in human small bowel.

BACKGROUND: Plant sterols are natural dietary components with serum cholesterol-lowering properties. The lowering of serum cholesterol by plant sterols is believed to be the result of an inhibition of cholesterol absorption in the small bowel, although increased bile acid excretion has also been suggested. The difference in effect of saturated and unsaturated plant sterols on cholesterol absorption needs to be elucidated further. OBJECTIVE: The primary aim of this study was to measure small-bowel cholesterol absorption and sterol excretion in addition to hepatic cholesterol synthesis after intake of soy sterol esters and beta-sitostanol ester corresponding to 1.5 g plant sterols/d. DESIGN: Seven ileostomy subjects were studied during a control period and 2 intervention periods when either soy sterol esters or beta-sitostanol ester was added to a basal diet. Ileostomy bags were collected every other hour and frozen immediately for analysis of nutrients and sterols. RESULTS: Cholesterol absorption was 56% (43-65%) in the control period and decreased to 38% (32-46%) in the soy sterol ester period (P = 0.00) and to 39% (30-48%) in the beta-sitostanol ester period (P = 0.00). CONCLUSION: Esterified soy sterols and beta-sitostanol inhibited cholesterol absorption equally, despite the different structures of the plant sterols.

Adult↗

ERGIC-53 and traffic in the secretory pathway.

The ER-Golgi intermediate compartment (ERGIC) marker ERGIC-53 is a mannose-specific membrane lectin operating as a cargo receptor for the transport of glycoproteins from the ER to the ERGIC. Lack of functional ERGIC-53 leads to a selective defect in secretion of glycoproteins in cultured cells and to hemophilia in humans. Beyond its interest as a transport receptor, ERGIC-53 is an attractive probe for studying numerous aspects of protein trafficking in the secretory pathway, including traffic routes, mechanisms of anterograde and retrograde traffic, retention of proteins in the ER, and the function of the ERGIC. Understanding these fundamental processes of cell biology will be crucial for the elucidation and treatment of many inherited and acquired diseases, such as cystic fibrosis, Alzheimer's disease and viral infections.

Animals↗

Protein targeting to endoplasmic reticulum by dilysine signals involves direct retention in addition to retrieval.

Dilysine signals confer localization of type I membrane proteins to the endoplasmic reticulum (ER). According to the prevailing model these signals target proteins to the ER by COP I-mediated retrieval from post-ER compartments, whereas the actual retention mechanism in the ER is unknown. We expressed chimeric membrane proteins with a C-terminal -Lys-Lys-Ala-Ala (KKAA) or -Lys-Lys-Phe-Phe (KKFF) dilysine signal in Lec-1 cells. Unlike KKFF constructs, which had access to post-ER compartments, the KKAA chimeras were localized to the ER by confocal microscopy and were neither processed by cis-Golgi-specific enzymes in vivo nor included into ER-derived transport vesicles in an in vitro budding assay, suggesting that KKAA-bearing proteins are permanently retained in the ER. The ER localization was nonsaturable and exclusively mediated by the dilysine signal because mutating the lysines to alanines led to cell surface expression of the chimeras. Although the KKAA signal avidly binds COP I in vitro, the ER retention by this signal does not depend on intact COP I in vivo because it was not affected in an epsilon-COP-deficient cell line. We propose that dilysine ER targeting signals can mediate ER retention in addition to retrieval.

Biological Transport↗

Effects of adrenocorticotrophin (ACTH) and progesterone on luteinising hormone (LH) secretion in recently castrated rams.

The goal of the present study was to determine whether ACTH and progesterone have any effect on LH secretion and pulse frequency in recently castrated rams. Six 2-year-old Corriedale rams were castrated in the winter. The day before castration, blood samples were taken in order to establish the precastration LH levels. The rams were divided into an untreated group (group U: n = 2) and a treated group (group T: n = 4). The first treatment consisted of the i.v. administration of 0.5 mg of ACTH on day 20 post-castration, immediately after the first sample had been taken. During the second treatment, subcutaneous progesterone implants were given to group T for 5 days. Control samplings were performed one week before each treatment. Prior to castration, the testosterone levels were low, while after castration they were below the detection limit of the assay. Cortisol and progesterone concentrations were basal before castration in all of the animals and after castration in group U and also in the control samplings for group T. ACTH treatment caused a significant increase in both cortisol and progesterone levels for 3 h (P < 0.001). Progesterone implants raised progesterone levels in group T, but cortisol levels remained basal. Before castration, all animals had low LH levels and hardly any pulse activity was seen. After castration, both the number of LH pulses and the mean LH production increased significantly in all of the animals (P < 0.01). During the ACTH trial, LH pulse frequency was significantly reduced for the first 4 h following ACTH administration (P = 0.013), however, no such differences occurred in the prior control period. No effect was seen on mean LH concentration during the ACTH treatment. Progesterone treatment did not have any effect on either the number of LH pulses nor on LH concentrations (P > 0.05).

Adrenocorticotropic Hormone↗

Plant sterols in vegetables and fruits commonly consumed in Sweden.

Plant sterols are known to have serum cholesterol lowering effects. A high dietary intake might therefore have a positive impact on health. All food items of vegetable origin contain some amount of plant sterols. The aim of this study was to analyse the plant sterol content of vegetables and fruits commonly consumed in Sweden, and to compare fresh and cooked samples of the same items. Altogether 20 different vegetables and 14 fruits were analysed. All vegetables and fruits were purchased in two shops in the city of Gothenburg, Sweden. Lyophilization was performed within one month of the items being purchased. The samples were frozen at -20 (C and analysed within six months, with a GLC method after acid hydrolysis, alkaline hydrolysis and silylation with tri-methylsilylether. The acid hydrolysis was done in order to detect the fraction of glycosylated plant sterols, which are split during boiling with HCl. The median plant sterol content of vegetables was 14 (3.8-50) mg/100 g edible portion. The highest concentrations were found in broccoli. Brussels sprouts, cauliflower and olives. The median plant sterol content of fruits was 16 (3-44) mg/100 g edible portion. The highest concentrations were found in oranges and passion fruits. The plant sterol concentrations were thus low in vegetables and fruits commonly consumed in Sweden. A serum cholesterol lowering effect attributed to the plant sterols in vegetables and fruits would therefore be of limited significance.

Animals↗

Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial.

A randomised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate (MA) on the quality of life (QoL), appetite, weight and survival of patients with advanced, incurable, hormone-insensitive cancer. QoL was assessed at the start of treatment and at 4, 8 and 12 weeks, using the EORTC-QLQ-C30 instrument. 255 patients were randomised to 320 mg of MA daily or placebo for 12 weeks. 244 patients were assessable at baseline, 190 at 4 weeks (placebo 94; MA 96), 150 at 8 weeks (placebo 69; MA 81) and 112 at 12 weeks (placebo 55; MA 57). A beneficial effect of MA on appetite loss was observed at week 4 (P < 0.0001) and possibly at week 8 (P = 0.058). Further weight loss during treatment was significant only in the placebo group. In the first 8 weeks, changes in mean global QoL were small and similar in both groups. By 12 weeks the decrease in mean global QoL was more pronounced in the MA group (P = 0.028), which was related to a deterioration in physical function, while psychosocial function was not affected. Survival was not affected by MA, and side-effects were mild. The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity. However, MA does not appear to improve global QoL as measured by the EORTC QLQ-C30.

Adult↗

The lectin ERGIC-53 is a cargo transport receptor for glycoproteins.

Soluble secretory proteins are transported from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) in vesicles coated with COP-II coat proteins. The sorting of secretory cargo into these vesicles is thought to involve transmembrane cargo-receptor proteins. Here we show that a cathepsin-Z-related glycoprotein binds to the recycling, mannose-specific membrane lectin ERGIC-53. Binding occurs in the ER, is carbohydrate- and calcium-ion-dependent and is affected by untrimmed glucose residues. Binding does not, however, require oligomerization of ERGIC-53, although oligomerization is required for exit of ERGIC-53 from the ER. Dissociation of ERGIC-53 occurs in the ERGIC and is delayed if ERGIC-53 is mislocalized to the ER. These results strongly indicate that ERGIC-53 may function as a receptor facilitating ER-to-ERGIC transport of soluble glycoprotein cargo.

Amino Acid Sequence↗

Biokinetics of the monoclonal antibodies MOv 18, OV 185 and OV 197 labelled with 125I according to the m-MeATE method or the Iodogen method in nude mice with ovarian cancer xenografts.

The biodistribution of the radiolabelled monoclonal antibodies MOv18, OV185 and OV197 in nude mice with subcutaneous tumours of the human ovarian cancer cell line OVCAR3 was investigated. The early uptake of MOv18 (1-24 h) and the uptake in relation to tumour size were also studied. The antibodies were labelled with 125I according to the Iodogen method or the m-MeATE method, the latter also being suitable for labelling with 211Astatine. The tumour/blood ratio and the localization index for Mov 18 72 h after antibody injection were 2.21 +/- 0.25 and 4.62 +/- 1.27, respectively. This is significantly higher than for the other two specific antibodies. The early tumour uptake of MOv18 was low with a tumour/blood ratio of 0.23 +/- 0.04 after 6 h, and the uptake was higher in small tumours. The two labelling methods were found to be equivalent. We conclude that MOv18 labelled according the m-MeATE method should be suitable for further therapeutic studies with 211Astatine in nude mice.

Animals↗