Dexamethasone for postoperative nausea and vomiting prophylaxis in cesarean delivery and a delayed diagnosis of neonatal congenital adrenal hyperplasia.

The case of a false-negative newborn screen for congenital adrenal hyperplasia in a 37 weeks' gestation 46,XX neonate, thought to be due to maternal administration of dexamethasone intra-operatively prior to umbilical cord clamping, for postoperative nausea and vomiting prophylaxis after neuraxial anesthesia, is described.

Immediate versus delayed removal of urinary catheter after laparoscopic hysterectomy: a randomised controlled trial.

OBJECTIVE: To evaluate if immediate catheter removal (ICR) after laparoscopic hysterectomy is associated with similar retention outcomes compared with delayed removal (DCR). STUDY DESIGN: Non-inferiority randomised controlled trial. POPULATION: Women undergoing laparoscopic hysterectomy in six hospitals in the Netherlands. METHODS: Women were randomised to ICR or DCR (between 18 and 24 hours after surgery). PRIMARY OUTCOME: The inability to void within 6 hours after catheter removal. RESULTS: One hundred and fifty-five women were randomised to ICR (n = 74) and DCR (n = 81). The intention-to-treat and per-protocol analysis could not demonstrate the non-inferiority of ICR: ten women with ICR could not urinate spontaneously within 6 hours compared with none in the delayed group (risk difference 13.5%, 5.6-24.8, P = 0.88). However, seven of these women could void spontaneously within 9 hours without additional intervention. Regarding the secondary outcomes, eight women from the delayed group requested earlier catheter removal because of complaints (9.9%). Three women with ICR (4.1%) had a urinary tract infection postoperatively versus eight with DCR (9.9%, risk difference -5.8%, -15.1 to 3.5, P = 0.215). Women with ICR mobilised significantly earlier (5.7 hours, 0.8-23.3 versus 21.0 hours, 1.4-29.9; P ≤ 0.001). CONCLUSION: The non-inferiority of ICR could not be demonstrated in terms of urinary retention 6 hours after procedure. However, 70% of the women with voiding difficulties could void spontaneously within 9 hours after laparoscopic hysterectomy. It is therefore questionable if all observed urinary retention cases were clinically relevant. As a result, the clinical advantages of ICR may still outweigh the risk of bladder retention and it should therefore be considered after uncomplicated laparoscopic hysterectomy. TWEETABLE ABSTRACT: The advantages of immediate catheter removal after laparoscopic hysterectomy seem to outweigh the risk of bladder retention.

Validation of ELISA methods for quantification of the major birch allergen Bet v 1 (BSP090).

To date, the potency of allergen products in Europe is expressed in manufacturer-specific units relative to a product-specific in-house reference. Consequently, cross-product comparability of allergen products from different manufacturers with respect to strength and efficacy is impossible. The Biological Standardisation Programme (BSP) project BSP090 addresses this issue via the establishment of reference standards in conjunction with ELISA methods for the quantification of major allergens in allergen products. Since the initiation of BSP090, the recombinant major allergen Bet v 1 has been adopted by the European Pharmacopoeia Commission as a Chemical Reference Substance (CRS). In parallel, two sandwich ELISA systems for quantification of Bet v 1 were found suitable in preliminary phases of BSP090 to be validated in a large collaborative study. In this study, the candidate ELISA systems were compared with respect to accuracy, precision and variability. Thirteen participating laboratories tested model samples containing the CRS as well as spiked and unspiked birch pollen extracts. Both in pre-testing and in the collaborative study, the 2 candidate ELISA systems confirmed their suitability to quantify recombinant and native Bet v 1. As no clear-cut decision for one of the ELISA systems could be made based on the results of the collaborative study, a post-study testing was performed. Bet v 1 content of 30 birch pollen allergen products was determined in parallel in both ELISA systems. Consequently, 1 candidate ELISA system was selected to be proposed as the future European Pharmacopoeia standard method for Bet v 1 quantification.

[Optimising postoperative recovery at home; individualised discharge policy and task division between GP and medical specialist]. / Optimaliseren van postoperatief herstel thuis.

In the last decennia, the length of hospital stay of admitted patients has significantly decreased in all medical fields. As a result, postoperative recovery mainly takes place at home, inherently leading to new challenges. Here, two patients are being discussed for whom the postoperative period was substandard. To guarantee optimal quality of care in the home situation, the medical specialist and the general practitioner need to make the necessary arrangements. We would first of all recommend providing each discharged patient with specific, structured and individualised advices regarding postoperative recovery but also regarding alarm symptoms and logistics (e.g. who to call in case of emergency). Finally, we believe that, as (serious) complications are rare, it should be agreed on the fact that the responsible medical specialist is the coordinator of the postoperative period and the first contact point for postoperative patients.

Disseminated leiomyoma cells can be identified following conventional myomectomy.

OBJECTIVE: Uncontained morcellation of leiomyomas during laparoscopic surgery has recently been discouraged, as undetected malignant tumours, namely leiomyosarcomas, could be fragmented which may result in upstaged disease. However, enucleating leiomyomas per se may be inappropriate from an oncological perspective because complete, radical resection of malignant tumours to prevent further tumour growth or recurrence is not achieved. Thus, the aim of this study was to determine whether spillage of leiomyoma cells occurs during laparotomic myomectomy. DESIGN: Observational study. SETTING: Tertiary academic centre in the Netherlands. POPULATION: Women undergoing laparotomic myomectomy were included in the study. METHODS: Peritoneal abdominal washings were obtained on two occasions during the myomectomy procedure; the first one immediately after opening the abdomen and the second one after resection of the leiomyoma(s). Cytological evaluation of the fluids was performed. MAIN OUTCOME MEASURES: The presence of leiomyoma cells in any of the washings. RESULTS: Five patients were included in this pilot study. All first washings were negative for leiomyoma cells. However, cytology positive for the presence of leiomyoma cells was found in three of the five second, post-myomectomy washings. CONCLUSION: Tissue spillage from leiomyoma(s) occurs during conventional open myomectomy. The clinical relevance of tissue dissemination after myomectomy is unclear but it cannot be excluded that this may negatively affect the patient's outcome if there is malignant change within the enucleated leiomyoma(s). Therefore, it is questionable whether morcellation in specially designed containment bags after laparoscopic myomectomy, guarantees any additional oncological safety. TWEETABLE ABSTRACT: Even during conventional myomectomy, tissue spillage occurs during resection of leiomyoma(s).

Effects of litter provision during early rearing and environmental enrichment during the production phase on feather pecking and feather damage in laying hens.

Feather pecking is a multi-factorial behavioral disorder and a serious welfare issue in the poultry industry. Several studies report early life experience with litter to be a major determinant in the development of feather pecking. The current study aimed to test the large-scale on-farm efficiency of a simple and cheap husbandry procedure applied during the rearing period with the ultimate goal of reducing the incidence of feather pecking and plumage damage during the production stage in laying hens. Five laying hen-rearing farmers from across Norway participated in the study. These farmers were asked to create divisions within their hen rearing houses and to separate their chicks into 2 groups: one reared with access to a paper substrate from the first d of age, the other a control group without access to paper substrate during rearing. All flocks were visited at the production farms at 30 wk of age and observed for pecking behavior and feather damage. Birds in the control group had higher odds of having more feather damage compared to the birds from the treatment group. In addition, flocks provided with environmental enrichment at the production farms had a reduced incidence of feather pecking, irrespective of the treatment. These results indicate that husbandry procedures during both rearing and production stages have the potential to alleviate feather pecking and increase laying hen welfare.

Milk processing quality of suckled/milked goats: effects of milk accumulation interval and milking regime.

Milk with a high concentration of fat and casein is required for cheese production, and these components have a major impact for both quality and yield of the curd. Recent observations have shown that suckling can elevate milk fat concentration in goats and our aim was therefore to check the hypothesis that animal welfare and cheese-processing properties of goat milk could be optimised by appropriate management of suckled/milked goats. Twelve Swedish dairy goats were kept together with one kid each in 4 different mixed management-systems (milking combined with partial suckling) in a cross-over design. Two milk accumulation intervals were tested; Short = dams and kids were together for 16 h (T16) and Long = ; dams and kids were together for 8 h (T8 h). In addition, two milking regimes were used; Suckled Before Milking = S and Milked Before Suckling = M. Milk accumulation interval referred to how long dams and kids were separated. The milk yield available for processing (milk offtake), was weighed and analysed from each milking occasion and the suckled milk yield was estimated by a weigh-suckle-weigh method (WSW) in combination with observing the suckling behaviour during the free suckling periods. Milking managements, such as 'suckling before milking (S)', increased milk fat concentration compared to milking before suckling (M) and 'Short accumulation treatments (T16)' gave higher milk fat, casein concentration and individual curd yield (%) compared to the 'Long accumulation treatment (T8)'. The total individual curd yield (g) was the same despite treatment, but the animal welfare was most likely higher in T16 where dams and kids spent more time together.

Standardization of allergen products: 3. Validation of candidate European Pharmacopoeia standard methods for quantification of major birch allergen Bet v 1.

BACKGROUND: The BSP090 project aims at establishing European Pharmacopoeia Reference Substances in combination with the corresponding ELISA methods for the quantification of major allergens in allergen products. Two sandwich ELISAs proved suitable for quantification of Bet v 1, the major birch pollen allergen, in preceding phases of BSP090. METHODS: Two Bet v 1-specific ELISA systems were compared with respect to accuracy and precision in a ring trial including 13 laboratories. Model samples containing recombinant rBet v 1.0101 as well as native birch pollen extracts were measured independently at least three times in each facility. The assessment was completed with a comparative quantification of Bet v 1 in 30 marketed birch allergen products in one laboratory, simulating the future use as reference method. RESULTS: In the collaborative study, both candidate ELISAs confirmed their suitability to quantify recombinant and native Bet v 1. ELISA-A showed higher precision and lower interlaboratory variability, yet ELISA-B exhibited slightly higher accuracy. Subsequent parallel measurement of Bet v 1 in a panel of 'real-life' birch allergen products indicated better repeatability of ELISA-B. Both systems detected substantial differences in Bet v 1 content between allergen products, but the effect was more pronounced using ELISA-B due to persistently higher values compared to ELISA-A. CONCLUSIONS: In the collaborative study, no deciding differences were observed between the two candidate ELISAs. Further comparison under conditions simulating the intended use combined with the criterion of long-term availability enabled the selection of one Bet v 1-specific ELISA for proposal as European Pharmacopoeia standard method.

Methadone in healthy goats - pharmacokinetics, behaviour and blood pressure.

The pharmacokinetics and effects of the opioid methadone on behaviour, arterial blood pressure, heart rate and haematocrit were studied in goats. Two goats received methadone (0.2mg/kg) intravenously and the terminal half-life was 88 and 91 min, the volume of distribution 8.4 and 6.1L/kg, and clearance 86 and 123 mL/min/kg. In a crossover study eight goats received methadone (0.6 mg/kg) or 0.15M NaCl subcutaneously (SC). After SC administration bioavailability was complete and the terminal half-life was 215 ± 84 min (mean ± SD), Tmax 31 ± 15 min and Cmax 45 ±11 ng/mL. Blood pressure and haematocrit increased while heart rate did not change. The goats did not ruminate and they climbed, scratched, gnawed and showed tail-flicking after SC methadone in contrast to NaCl administration. The use of methadone in goats may be restricted due to the inhibition of rumination and the rather short half-life.

A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1.

Brain-specific angiogenesis inhibitor 1 (BAI1), an orphan G protein-coupled receptor-type seven transmembrane protein, was recently found mutated or silenced in multiple human cancers and can interfere with tumor growth when overexpressed. Yet, little is known about its regulation and the molecular mechanisms through which this novel tumor suppressor exerts its anti-cancer effects. Here, we demonstrate that the N terminus of BAI1 is cleaved extracellularly to generate a truncated receptor and a 40-kDa fragment (Vasculostatin-40) that inhibits angiogenesis. We demonstrate that this novel proteolytic processing event depends on a two-step cascade of protease activation: proprotein convertases, primarily furin, activate latent matrix metalloproteinase-14, which then directly cleaves BAI1 to release the bioactive fragment. These findings significantly augment our knowledge of BAI1 by showing a novel post-translational mechanism regulating BAI1 activity through cancer-associated proteases, have important implications for BAI1 function and regulation, and present novel opportunities for therapy of cancer and other vascular diseases.

Calibration of the human immunoglobulin BRPs for ACA and molecular size (batch 1) and for Fc function and molecular size (batches 1 & 2).

The current European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation batch 3 (BRP3) for Human Immunoglobulin was established in 2005. Stocks of this BRP are dwindling and a replacement batch is needed to serve as working standard in the tests for distribution of molecular size by HPLC, anticomplementary activity (ACA) and Fc function, in accordance with the requirements of the Ph. Eur. monographs Human normal immunoglobulin (0338) and Human normal immunoglobulin for intravenous administration (0918). The European Directorate for the Quality of Medicines & HealthCare (EDQM) carried out a project (BSP099) to establish replacement batches for this BRP. The project was run in 2 phases, a prequalification phase (Phase 1) and an international collaborative study (Phase 2) involving 19 laboratories. Three batches of candidate materials of various sizes, Samples A, B and C, were procured from 2 different manufacturers on the European market. Based on the results of the study, Sample A was shown to be suitable as a reference standard for the ACA test and for molecular size determination by HPLC, whereas Samples B and C were demonstrated to be suitable for the Fc function test and for the molecular size determination by HPLC. All 3 BRPs are to be used in conjunction with the monographs Human normal immunoglobulin (0338) and Human normal immunoglobulin for intravenous administration (0918). The BRPs were adopted by the Ph. Eur. Commission at its 141st session in November 2011 as official Ph. Eur. Human Immunoglobulin BRPs for ACA and molecular size Batch 1 (Sample A) and Fc function and molecular size Batch 1 and Batch 2 (Samples B and C respectively).

Clinical pharmacology of buprenorphine in healthy, lactating goats.

The pharmacokinetics and the effects of the opioid buprenorphine on behavior, cardiovascular parameters, plasma concentrations of cortisol and vasopressin were studied in the goat. After intravenous injection at a dosage of 0.02 mg/kg bw, the terminal half-life was 73.8+/-19.9 min (mean+/-SD), the apparent volume of distribution 5.22+/-1.01 L/kg, and total body clearance 79.1+/-18.5 mL/min/kg. After intramuscular administration of buprenorphine at the same dosage, bioavailability was complete and clearance was 54.7+/-16.6 mL/min/kg. Heart rate, blood pressure and concentrations of cortisol and vasopressin in plasma increased after drug administration. The goats became agitated and stopped ruminating. The effects were more pronounced the first time the animals received the drug, especially the influence on the hormone levels. The concentrations of cortisol and vasopressin in plasma remained unaffected after the second dose despite a wash-out period of 3-6 weeks. Buprenorphine may be an unsuitable drug in goats because of the profound inhibition of rumination and the agitation it causes. The short half-life of buprenorphine may limit its use if long-term analgesia is required but be advantageous if a short acting drug is desirable.

Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer.

Until recently, fluorouracil (F) and leucovorin (L) had been considered the standard therapy for patients with colorectal cancer. However, several studies have shown that oral therapy with UFT/L or capecitabine is as effective as intravenous (i.v.) therapy and in addition it is claimed that patients prefer oral to i.v. therapy as long as efficacy is not compromised. In a previous crossover study by Borner et al., it was shown that 26 out of 31 patients preferred oral therapy with UFT/L to i.v. FL (Mayo regimen) [Borner M, Schöffski P, de Wit R, et al. Patient preferences and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002;38:349-58]. The objective of the present study was to investigate patient preference between i.v. FL and oral capecitabine using the design described by Borner. The Nordic FL schedule is a bolus regimen with efficacy comparable to other i.v. regimens and at the same time a very tolerable and easy administered regimen. We randomised 60 patients with colorectal cancer (53 patients received adjuvant therapy and seven patients received palliative therapy) to start therapy with either oral capecitabine or Nordic bolus FL. After 6 weeks of therapy (two courses of capecitabine or three courses of Nordic FL) patients were crossed over to the other regimen. After having completed 12 weeks of therapy the patients (49 evaluable patients) were asked to choose one of the regimens for a further 12 weeks of therapy. Patients had more side-effect when treated with capecitabine and a total of 30 out of 49 (61%) preferred the Nordic FL regimen and 19 (39%) preferred capecitabine. We conclude that patients prefer the regimen with less toxicity and that it is of minor importance whether the medication is administrated orally at home or i.v. at the hospital.

Application of HEMA on intact mouse skin--effects on the immune system.

Previously, we have shown that 2-hydroxyethylmethacrylate (HEMA) can bind to protein and that autoantibodies were induced in mice by immunization with a self-protein in vitro conjugated with HEMA. The present study aimed to develop a model for HEMA-induced sensitivity by the application of the substance on intact skin. Female BALB/c mice were painted on the dorsum of each ear with 50% HEMA in vehicle twice a week for 6 weeks. The anti-CD3epsilon-stimulated lymph node production and the spontaneous spleen-cell production of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-10 and interferon-gamma were assessed by enzyme-linked immunosorbent assay. In another experiment, the cytokines were followed after subcutaneous HEMA injections. Animals painted with HEMA had a significantly higher IL-6 production by anti-CD3epsilon-stimulated lymph node cells and significantly suppressed IL-10 production by spleen cells compared to vehicle-treated mice. This correlated to some extent with the spontaneous spleen-cell production induced by subcutaneously administered HEMA. An injection of 20 micromol of HEMA induced an increased production of IL-6, while injection of 40 micromol depressed both IL-6 and IL-10 production. Although there was no sign of inflammation on the ears, findings suggest that HEMA had penetrated the skin and induced a reaction in the immune system.

Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP batch 1.

A study was carried out by the European Directorate for the Quality of Medicines (EDQM) as part of the joint Biological Standardisation Programme of the Council of Europe and the European Commission with the aim to establish replacement batches of the European Pharmacopoeia (Ph. Eur.) human immunoglobulin Biological Reference Preparation (BRP) batch 2. Twenty-eight laboratories participated in this study. The suitability of the candidate reference preparations to serve as working references in the tests for distribution of the molecular size, anticomplementary activity and Fc function, in accordance with the specifications of the Ph. Eur. monographs Human normal immunoglobulin for intravenous administration (0918), Human normal immunoglobulin (0338) and Anti-T lymphocyte immunoglobulin for human use, animal (1928) was demonstrated. The candidates were therefore established as human immunoglobulin BRP batch 3 and Human immunoglobulin (molecular size) BRP batch 1. The prescribed use of the latter BRP is limited to the test for distribution of molecular size.

Low HEMA conjugation induces high autoantibody titer in mice.

2-hydroxyethylmethacrylate (HEMA) is a known causal agent of hypersensitivity to resin composites. We have reported that immunization with HEMA conjugated to mouse serum albumin (MSA) induces an autoantibody response in mice. In this study, we investigated both the activity and the avidity of autoantibodies induced by immunization with various HEMA conjugations to MSA. Female Balb/c mice were given MSA carrying 3, 7, 15, or 22 HEMA molecules. Antigen-specific IgG and IgE antibodies were determined by ELISA, and average antibody avidity by thiocyanate dissociation. Immunization with MSA carrying the lowest number of HEMA molecules induced a significantly higher IgG and IgE anti-MSA autoantibody response, with significantly higher IgG antibody avidity, than did the more heavily conjugated preparations. The results suggest that the lower the degree of HEMA conjugation to self-protein, the higher the risk for autoantibody production to the carrier protein. These findings suggest a mechanism of potential relevance in humans.

Physiological reactions to fear provocation in dogs.

Fear is a common behavioral problem in dogs. In this paper, we studied the association between behavioral and physiological responses in two potentially fear-eliciting situations. The aim was to establish whether it is possible to separate dogs of the collie breed that are fearful of floors and gunshots from those that are not by studying changes in heart rate and hematocrit, plasma cortisol, progesterone, testosterone, vasopressin, and beta-endorphin concentrations. Thirteen privately owned male dogs of the collie breed were studied during a floor test, using different types of floors, and a subsequent gunshot test. Seven of the dogs were identified as being fearful of floors and six were declared as fearless. Out of the 13 dogs, seven were fearful of gunshots and six were fearless of gunshots. Since fear of floors did not always occur concomitantly with fear of gunshots, there were consequently four different groups of dogs. The heart rate increased during the floor test in all groups, but dogs that were fearful of floors had higher heart rates than dogs that were fearless of floors. Dogs that were fearful of gunshots had higher heart rates, higher hematocrit levels and higher plasma concentrations of cortisol, progesterone, vasopressin, and beta-endorphins during the gunshot test than did dogs that were found to be fearless of gunshots. Plasma cortisol and progesterone increased drastically during the gunshot test in dogs identified as being fearful of gunshots. In fearful dogs, the testosterone concentration increased after completion of the floor test and before the gunshot test started, but there were no significant differences in testosterone between the groups. Since dogs fearful of gunshots had increased levels of several physiological parameters, the results demonstrated that this fear is a serious stress for the individual, a fear which it is possible to register with physiological variables.

Measurement of polarization with the Degree Angular Scale Interferometer.

Measurements of the cosmic microwave background (CMB) radiation can reveal with remarkable precision the conditions of the Universe when it was approximately 400,000 years old. The three most fundamental properties of the CMB are its frequency spectrum (which determines the temperature), and the fluctuations in both the temperature and polarization across a range of angular scales. The frequency spectrum has been well determined, and considerable progress has been made in measuring the power spectrum of the temperature fluctuations. But despite many efforts to measure the polarization, detection of this property of the CMB has hitherto been beyond the reach of even the most sensitive observations. Here we describe the Degree Angular Scale Interferometer (DASI), an array of radio telescopes, which for the past two years has conducted polarization-sensitive observations of the CMB from the Amundsen-Scott South Pole research station.