Hepatitis B seroprevalence in persons attending youth clinics in Stockholm, Sweden in 2008.

Sweden is a low endemicity country for hepatitis B virus (HBV). The previously reported prevalence of chronic HBV is <1% and of overall markers <5%. HBV is not included in the universal childhood vaccination programme. Instead, selected high-risk groups are targeted. Our aim was to examine the HBV seroprevalence in youth clinic clients in Stockholm and identify if this population might be a new target group for vaccination. In total, 515 clients aged 18-22 years were recruited. They completed a risk-assessment questionnaire and 464 (90%) had a serum specimen tested for HBV serology. Chronic HBV was found in 0.6% and 0.9% had previously been infected with HBV. A seroprevalence of 1.8% HBV markers was found among non-vaccinated persons. This is lower than reported from other countries and not different from the general population in Sweden. However, in persons originating from HBV endemic countries (n = 123), the prevalence was higher, 6.5%. Only 14% were vaccinated and the majority hence susceptible to HBV. The target groups are not reached by the present vaccination strategy. Youth clinics are ideal settings for catch-up vaccination.

Identification and purity test of heparin by NMR - a summary of two years' experience at the Medical Products Agency.

This paper is a review of published and unpublished results on heparin during the last two years. Results and experiences gathered in our laboratory at MPA in Sweden, from the collaborative NMR study on heparin in Europe (coordinated by EDQM), and from the process of drafting heparin Ph. Eur. monograph texts where new ideas and experiments have been performed. Explanations and guidelines are also presented to clarify the NMR identification test introduced in the sodium and calcium heparin monographs. NMR, strong anion exchange-LC (SAX-LC) and capillary electrophoresis (CE) have been compared in the quantification of over-sulphated chondroitin sulphate (OSCS) and dermatan sulphate (DS) in heparin. In this paper, the term heparin will stand for unfractionated porcine heparin sodium. When other heparin types are mentioned, they will be explicitly named.

Dominant expression and distribution of oestrogen receptor beta over oestrogen receptor alpha in the human corpus luteum.

To investigate the potential importance of oestrogen as a local regulator of human corpus luteum function, the mRNA expression pattern and cellular localization of oestrogen receptors (ERs), ER-alpha and ER-beta, were studied in corpora lutea grouped according to age, where days 2-5 post-LH rise were designated as the early luteal phase, days 6-10 as mid-luteal and days 11-14 as the late luteal phase respectively. Northern blot analysis using an ER-beta probe in samples from whole ovarian tissue and isolated corpora lutea, revealed a major band at 7.5 kb and several minor bands between 4-10 kb, while no signals for ER-alpha mRNA were obtained. However, using a semi-quantitative reverse transcription-polymerase chain reaction followed by Southern blotting, ER-beta mRNA levels were found to be 63% lower (P: < 0.05, n = 39) in the mid-luteal phase compared with the early luteal phase, while ER-alpha mRNA expression showed no statistical differences between the different age groups. Using in-situ hybridization, ER-beta mRNA expression was localized to the steroidogenic luteal cells as well as perivascular cells and fibroblasts in the corpus luteum. Immunohistochemistry confirmed the localization of ER-beta protein, but no clear staining of luteal cells was found using antibodies against ER-alpha. Collectively, the findings of low to moderate expression of ER-beta mRNA and protein in the steroidogenic cells, and also in vascular endothelial cells of the corpus luteum, as opposed to diminutive amounts of ER-alpha mRNA, suggest that oestrogen activity is primarily transduced via ER-beta in the human corpus luteum.

Dose selection for carcinogenicity studies of pharmaceuticals: systemic exposure to phenacetin at carcinogenic dosage in the rat.

A systemic exposure-based alternative to the MTD (maximally tolerated dose) for high-dose selection in carcinogenicity studies of pharmaceuticals has been accepted by the ICH (International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use). As a result of a retrospective analysis performed by the U.S. FDA (United States Food and Drug Administration), a rat/human relative systemic exposure ratio of 25 is proposed by the ICH as an acceptable pharmacokinetic endpoint for high-dose selection. For use as a dose selection criterion, it is particularly important that the magnitude of the relative systemic exposure ratio should be sufficient to detect human pharmaceuticals classified by IARC (International Agency for Research on Cancer, World Health Organization) as known (category 1) or probable (category 2A) human carcinogens. For one of these, phenacetin (an IARC 2A compound and a rat carcinogen), a systemic exposure ratio of 15 was calculated by the FDA. This calculation was based on a number of extrapolations. The present study reports the actual systemic exposure to phenacetin in the rat under conditions mimicking the conditions in the carcinogenicity study used by the FDA to calculate the relative systemic exposure ratio of 15. The ratio was found to be 7, indicating that the carcinogenic potential of this particular probable human carcinogen could be detected at a considerably lower systemic exposure ratio than that proposed by the ICH.

Survey of postoperative analgesia following ambulatory surgery.

BACKGROUND: The quality of pain relief during the first 48 hours following ambulatory surgery has been poorly documented. This questionnaire study was performed to evaluate the nature and severity of pain after the patient leaves the hospital. METHODS: 1100 patients in the age group 5-88 years who underwent ambulatory surgery during a period of 6 months were asked to complete a questionnaire 48 h after the end of the operation. In the case of children, parents were asked to complete a similar questionnaire. The questions were related to pain experienced during the first 48 h after surgery and to the nature and severity of postoperative complications. RESULTS: A total of 1035 out of the 1100 patients returned the questionnaire, 94.1%. Overall the majority (65%) of patients had only mild pain at home; however, patients undergoing certain types of surgery had moderate-to-severe pain: inguinal hernia surgery (62% patients), orthopaedic surgery (41%), hand surgery (37%) and varicose vein surgery (36%). In these patients the severity of pain did not decrease during the 2-day study period. About 10% patients had more severe pain than they had anticipated, and 20% had difficulty in sleeping at night due to severe pain. Despite this, over 95% of patients were satisfied with management of postoperative pain. Nausea (20%), tiredness (20%) and vomiting (8%) were the commonest complications reported during the first 48 h. A significant association was found between the administration of a general anaesthetic and the incidence of nausea postoperatively. A large number of patients were alone at home after the operation (28.4%); some (3.8%) had no access to a relative or friend in case of need. CONCLUSION: Our results show that about 35% of day-surgery patients experience moderate-to-severe pain at home in spite of analgesic medication. About 20% of patients had sleep problems due to severe pain. However, only 5% of patients were dissatisfied. Better analgesic techniques are necessary for patients undergoing certain types of surgery. Patient information and follow-up routines need to be improved.

Validation of different microdialysis methods for the determination of unbound steady-state concentrations of theophylline in blood and brain tissue.

Three microdialysis methods, the "tritium" method, the "point-of-no-net-flux" method, and a method using the low perfusion rate of 0.1 microliter/min, were compared with respect to their ability to generate estimates of unbound steady-state concentrations (Cu(ss)) of the antiasthmatic drug theophylline in blood and brain tissue in anesthetized rats. Concomitantly, the influence of the perfusion flow rate on the estimated extracellular Cu(ss) obtained with the point-of-no-net-flux method was investigated. Theophylline was administered as a rapid intravenous bolus dose followed by constant intravenous infusion. Changes in perfusion flow rate from 2.0 to 0.75 microliter/min and, finally, to 0.25 microliter/min, using the point-of-no-net-flux method, had no significant effect on the estimated Cu(ss) of theophylline in blood and striatum. This observation, particularly in the case of brain tissue, is not consistent with the theory that the process of dialysis drains a significant amount of substance from the immediate vicinity of the dialysis probe. Similar estimates of Cu(ss) in blood as well as in brain tissue were obtained with all three methods. Their accuracy in estimating Cu(ss) in blood was further strengthened by observations of unbound fractions similar to those reported in the literature. Furthermore, all three methods gave striatum/blood ratios at steady state of approximately 0.5, indicating that there is active transport of theophylline from brain tissue. It is concluded that the tritium method, when validated, can be used to study the time course of unbound drug concentrations in blood and tissues.

Pigmentation of kidneys and lymph nodes of mesocolon in rats fed diets containing the laxative danthron.

The tumor-promoting activity of the anthraquinone laxative danthron was studied by giving 3 groups of male rats a single subcutaneous injection of the colon tumor-inducing agent 1,2-dimethylhydrazine (DMH). After 1 week, the animals were fed diets containing 0, 600 or 2400 ppm of danthron for 26 weeks. Two other groups of rats were included in the study; one received no treatment while the other was given danthron only. Altogether 9 tumors were observed among animals given DMA with or without danthron. The incidence of colon tumors was higher in animals receiving DMH and danthron than in those given DMH only (5/60 vs. 0/30), but this difference was not statistically significant. The kidneys and lymph nodes of mesocolon were enlarged and showed a yellowish-red and brown discoloration, respectively. The pigment mostly displayed a PAS-positive reaction but contained no lipid as determined by several staining procedures. The available evidence suggests that the pigment is drug-derived.