The impact of different Hormonal Growth Promotants (HGP) on desmin degradation and collagen content of various muscles from pasture and feedlot finished steer carcasses.

The impacts of several hormonal growth promotants (HGP) on Warner-Bratzler Shear Force (WBSF), desmin degradation ratio (DDR) and collagen content (COLL) were assessed. Treatments within feedlot and pasture finished steer carcasses (n = 60, n = 40, respectively) were control (CON-100-F and CON-400-P), oestradiol HGPs (OES-100-F and OES-400-P) and trenbolone acetate/oestradiol HGPs (TBA+OES-100-F only). The longissimus lumborum (LL), gluteus medius (GM), infraspinatus (IS), semitendinosus (ST,) and the LL and biceps femoris (BF) were collected from feedlot and pasture finished steers, respectively. All muscles were aged between 3 and 35 days. The LL from TBA+OES-100-F carcasses had increased WBSF and decreased DDR, which varied in magnitude with ageing (P < 0.05). The GM from OES-100-F steers also had lower DDR (P < 0.05). The feedlot HGP treatments had no impact on the WBSF of the IS, ST or GM and no impact on COLL in the LL. The OES-400-P had no impact on WBSF, DDRor COLL for both muscles (P > 0.05).

The impact of oestradiol only hormone growth promotants (HGPs) on the eating quality of pasture finished steer carcasses.

A total of 200 Bos indicus/Bos taurus cross steers were allocated to control (CON) and an oestradiol (OES) implant treatments and pasture finished for 389 days. Longissimus lumborum (LL) and gluteus medius (GM) samples were aged for 5 and 35 days. Live weight, carcass weight and ossification scores (P < 0.05) increased in OES relative to CON. The three-way interaction between treatment, days aged and muscle was significant (P < 0.05) for tenderness, overall liking and meat palatability, whereby the OES had lower scores relative to CON at 5 days in LL (P < 0.05), although the difference halved by 35 days. For the GM, OES scores at 5 days were lower than CON (P < 0.05), apart from like flavour, and differences reduced by 35 days. LL shear force was higher for OES at 5 days (P < 0.05), though not 35 days (P > 0.05), or the GM at 5 or 35 days (P > 0.05). OES samples had a higher calpastatin activity (P < 0.05) in the LL at 19 h post mortem.

Smoking in pregnancy is a key factor for sudden infant death among Maori.

AIM: To examine the sudden unexpected death in infancy (SUDI) disparity between Maori and non-Maori in New Zealand. METHODS: A nationwide prospective case-control study ran from March 2012 to February 2015. Exposure to established SUDI risk factors was analysed to investigate the disparity experienced by Maori. Infant ethnicity was based on mother's ethnicity. Maori ethnicity was prioritised. Non-Maori includes Pacific, Asian, NZ European and Other. RESULTS: There were 137 cases and 649 controls. The Maori SUDI rate was 1.41/1000 live births compared to 0.53/1000 for non-Maori. Parents/caregivers of 132 cases (96%) and 258 controls (40%) were interviewed. Smoking in pregnancy was associated with an equally increased SUDI risk for Maori (adjusted OR = 8.11, 95% CI = 2.64, 24.93) and non-Maori (aOR = 5.09, 95% CI = 1.79, 14.47), as was bed-sharing (aOR = 3.66, 95% CI = 1.49, 9.00 vs aOR = 11.20, 95% CI = 3.46, 36.29). Bed-sharing prevalence was similar; however, more Maori controls smoked during pregnancy (46.7%) than non-Maori (22.8%). The main contributor relating to increased SUDI risk for Maori/non-Maori infants is the combination of smoking in pregnancy and bed sharing. CONCLUSION: The association between known SUDI risk factors, including bed sharing and/or smoking in pregnancy and SUDI risk, is the same regardless of ethnicity. Maori infants are exposed more frequently to both behaviours because of the higher Maori smoking rate.

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator.

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms do not incorporate respiratory gating, which is required for accurate and precise targeting in organs subject to respiration related motions that may be up to the order of 5 mm in mice. Therefore, a new treatment head assembly for the Xstrahl Small Animal Radiation Research Platform (SARRP) has been designed. This includes a fast X-ray shutter subsystem, a motorized beam hardening filter assembly, an integrated transmission ionization chamber to monitor beam delivery, a kinematically positioned removable beam collimator and a targeting laser exiting the center of the beam collimator. The X-ray shutter not only minimizes timing errors but also allows beam gating during imaging and treatment, with irradiation only taking place during the breathing cycle when tissue movement is minimal. The breathing related movement is monitored by measuring, using a synchronous detector/lock-in amplifier that processes diffuse reflectance light from a modulated light source. After thresholding of the resulting signal, delays are added around the inhalation/exhalation phases, enabling the "no movement" period to be isolated and to open the X-ray shutter. Irradiation can either be performed for a predetermined time of X-ray exposure, or through integration of a current from the transmission monitor ionization chamber (corrected locally for air density variations). The ability to successfully deliver respiratory-gated X-ray irradiations has been demonstrated by comparing movies obtained using planar X-ray imaging with and without respiratory gating, in addition to comparing dose profiles observed from a collimated beam on EBT3 radiochromic film mounted on the animal's chest. Altogether, the development of respiratory-gated irradiation facilitates improved dose delivery during animal movement and constitutes an important new tool for preclinical radiation studies. This approach is particularly well suited for irradiation of orthotopic tumors or other targets within the chest and abdomen where breathing related movement is significant.

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (CC-RCC) is the most lethal of all genitourinary cancers. The functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progression. The objective of this study was to identify chemical compounds that are synthetically lethal with VHL deficiency in CC-RCC. An annotated chemical library, the library of pharmacologically active compounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-introduced VHL. The ROCK inhibitor, Y-27632, was identified and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by clonogenic assays. Downregulation of ROCK1 by small interfering RNA (siRNA) selectively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-27632 treatment, whereas downregulation of ROCK2 had no effect. In addition, two other ROCK inhibitors, RKI 1447 and GSK 429286, selectively targeted VHL-deficient CC-RCC. CC-RCC treatment with ROCK inhibitors is cytotoxic and cytostatic based on bromodeoxyuridine (BrdU) assay, propidium iodide (PI) staining and growth curves, and blocks cell migration based on transwell assay. On the one hand, knockdown of hypoxia-inducible factor (HIF) ß in the VHL-deficient CC-RCC had a protective effect against Y-27632 treatment, mimicking VHL reintroduction. On the other hand, CC-RCCVHL cells were sensitized to Y-27632 treatment in hypoxia (2% O2). These results suggest that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC.

Evaluating the ORSIM® simulator for assessment of anaesthetists' skills in flexible bronchoscopy: aspects of validity and reliability.

BACKGROUND: Developing expertise in flexible bronchoscopy is limited by inadequate opportunities to train on difficult airways. The new ORSIM bronchoscopy simulator aims to address this by creating virtual patients with difficult airways. This study aims to provide evidence on the validity and reliability of the ORSIM for assessment of subjects on both normal and abnormal airway simulations. METHODS: Novice, trainee, and expert subjects performed seven simulations of varying difficulty and scored the perceived difficulty for each. Time to completion was measured. Three blinded raters independently scored videos of each subject's performance. We measured inter-rater agreement and the difference in raters' scores between subject groups. RESULTS: We recruited 28 study subjects, generating 196 videos for analysis. Expert subjects consistently completed the scenarios faster than novices. Overall performance scores showed significant differences between subject groups (P<0.0001). Inter-rater reliability of scores was >0.8. CONCLUSIONS: Our results provide initial evidence on the validity and reliability of the ORSIM bronchoscopy simulator, supporting its potential value in training and assessment.

Shear-wave elastography contributes to accurate tumour size estimation when assessing small breast cancers.

AIM: To assess whether the size of peritumoural stiffness (PTS) on shear-wave elastography (SWE) for small primary breast cancers (≤15 mm) was associated with size discrepancies between grey-scale ultrasound (GSUS) and final histological size and whether the addition of PTS size to GSUS size might result in more accurate tumour size estimation when compared to final histological size. MATERIALS AND METHODS: A retrospective analysis of 86 consecutive patients between August 2011 and February 2013 who underwent breast-conserving surgery for tumours of size ≤15 mm at ultrasound was carried out. The size of PTS stiffness was compared to mean GSUS size, mean histological size, and the extent of size discrepancy between GSUS and histology. PTS size and GSUS were combined and compared to the final histological size. RESULTS: PTS of >3 mm was associated with a larger mean final histological size (16 versus 11.3 mm, p < 0.001). PTS size of >3 mm was associated with a higher frequency of underestimation of final histological size by GSUS of >5 mm (63% versus 18%, p < 0.001). The combination of PTS and GSUS size led to accurate estimation of the final histological size (p = 0.03). The size of PTS was not associated with margin involvement (p = 0.27). CONCLUSION: PTS extending beyond 3 mm from the grey-scale abnormality is significantly associated with underestimation of tumour size of >5 mm for small invasive breast cancers. Taking into account the size of PTS also led to accurate estimation of the final histological size. Further studies are required to assess the relationship of the extent of SWE stiffness and margin status.

A low temperature, isothermal gas-phase system for conversion of methane to methanol over Cu-ZSM-5.

A low temperature, isothermal, gas-phase, recyclable process is described for the partial oxidation of methane to methanol over Cu-ZSM-5. Activation in NO at 150 °C followed by methane reaction and steam extraction (both at 150 °C) allowed direct observation of methanol at the reactor outlet.

SmartStretch™ technology. I. Improving the tenderness of sheep topsides (m. semimembranosus) using a meat stretching device.

This study evaluated the effect of stretching hot-boned sheep topsides using a pre-production prototype device (SmartStretch™). To test this effect, 40 sheep from 3 consignments were assessed. Left and right topsides were collected pre-rigour and randomly allocated to one of four treatments; 0 days ageing+SmartStretch™, 0 days ageing+no stretch, 5 days ageing+SmartStretch™ and 5 days ageing+no stretch. Meat from the 0 days aged+no stretch treatment was the least tender and the 5 days ageing+SmartStretch™ treatment resulted in the most tender meat. The m. semimembranosus from topsides stretched using the SmartStretch™ prototype device had a lower cooking loss percentage (P<0.001) and longer sarcomeres (P<0.001) than non-stretched m. semimembranosus. There was no effect of SmartStretch™ on myofibrillar degradation measured using particle size analysis (PSA), but there was an ageing effect (P<0.001). The tenderness of stretched m. semimembranosus showed significant improvement over non-stretched m. semimembranosus.

Dendritic cells and T cells deliver oncolytic reovirus for tumour killing despite pre-existing anti-viral immunity.

Reovirus is a naturally occurring oncolytic virus currently in early clinical trials. However, the rapid induction of neutralizing antibodies represents a major obstacle to successful systemic delivery. This study addresses, for the first time, the ability of cellular carriers in the form of T cells and dendritic cells (DC) to protect reovirus from systemic neutralization. In addition, the ability of these cellular carriers to manipulate the subsequent balance of anti-viral versus anti-tumour immune response is explored. Reovirus, either neat or loaded onto DC or T cells, was delivered intravenously into reovirus-naive or reovirus-immune C57Bl/6 mice bearing lymph node B16tk melanoma metastases. Three and 10 days after treatment, reovirus delivery, carrier cell trafficking, metastatic clearance and priming of anti-tumour/anti-viral immunity were assessed. In naive mice, reovirus delivered either neat or through cell carriage was detectable in the tumour-draining lymph nodes 3 days after treatment, though complete clearance of metastases was only obtained when the virus was delivered on T cells or mature DC (mDC); neat reovirus or loaded immature DC (iDC) gave only partial early tumour clearance. Furthermore, only T cells carrying reovirus generated anti-tumour immune responses and long-term tumour clearance; reovirus-loaded DC, in contrast, generated only an anti-viral immune response. In reovirus-immune mice, however, the results were different. Neat reovirus was completely ineffective as a therapy, whereas mDC--though not iDC--as well as T cells, effectively delivered reovirus to melanoma in vivo for therapy and anti-tumour immune priming. Moreover, mDC were more effective than T cells over a range of viral loads. These data show that systemically administered neat reovirus is not optimal for therapy, and that DC may be an appropriate vehicle for carriage of significant levels of reovirus to tumours. The pre-existing immune status against the virus is critical in determining the balance between anti-viral and anti-tumour immunity elicited when reovirus is delivered by cell carriage, and the viral dose and mode of delivery, as well as the immune status of patients, may profoundly affect the success of any clinical anti-tumour viral therapy. These findings are therefore of direct translational relevance for the future design of clinical trials.

Slow platelet recovery after PBPC transplantation from unrelated donors.

The effects of the composition of PBPC grafts from matched related donors (MRDs) and matched unrelated donors (MUDs) have not been compared. In a single-center study, the compositions of 55 MRD PBPC grafts and 33 MUD grafts were studied for their effect on the rate of engraftment in patients who had evidence of donor cell engraftment on day +28. The MUD grafts came more frequently from young male donors and contained more CD34(+) cells but similar numbers of colony-forming units granulocyte-macrophage (CFU-GM) and burst forming units-erythroid. The recovery of neutrophils to >500/mm(3) was equally fast in both groups, but recovery of platelets to >20,000/mm(3) was significantly delayed in the MUD group (P<0.001). The MUD group also required more transfusions of platelets and red cells. Patients receiving grafts containing low numbers of CFU-GM had markedly delayed platelet recovery. The patients with the slowest engraftment tended to have prolonged transportation times. Storage experiments suggested a major loss of viable CD34(+) cells and CFU-GM when undiluted PBPC products are stored at room temperature. The data suggest that a fraction of the MUD grafts suffer during transportation. In vitro proliferation assays should be part of the validation and auditing of transportation of MUD grafts.

Dendritic cells and macrophages in the genitourinary tract.

Dendritic cells (DCs) and macrophages are antigen-presenting cells (APCs) that are important in innate immune defense as well as in the generation and regulation of adaptive immunity against a wide array of pathogens. The genitourinary (GU) tract, which serves an important reproductive function, is constantly exposed to numerous agents of sexually transmitted infections (STIs). To combat these STIs, several subsets of DCs and macrophages are strategically localized within the GU tract. In the female genital mucosa, recruitment and function of these APCs are uniquely governed by sex hormones. This review summarizes the latest advances in our understanding of DCs and macrophages in the GU tract with respect to their subsets, lineage, and function. In addition, we discuss the divergent roles of these cells in immune defense against STIs as well as in maternal tolerance to the fetus.

Synergy of adoptive T-cell therapy and intratumoral suicide gene therapy is mediated by host NK cells.

In situ tumor cell killing by the herpes simplex virus thymidine kinase (HSVtk) gene can effectively prime antitumor T-cell responses, at least in part through local induction of a pro-inflammatory environment. Therefore, we reasoned that tumor-associated HSVtk expression would significantly enhance the efficacy of adoptive T-cell transfer (ACT) of (tumor) antigen-specific T cells into tumor-bearing hosts. When B16ovaHSVtk tumors were treated with ganciclovir (GCV), along with suboptimal numbers of activated OT-1T cells, complete tumor regressions were observed where GCV, or ACT, alone was completely ineffective. To our surprise, analysis of regressing tumors showed no increases in intratumoral OT-1T cell trafficking. However, the intratumoral percentages of both OT-1 and endogenous natural killer (NK) cells were substantially increased over controls. Depletion of endogenous NK cells abrogated the efficacy of the combination therapy and reduced the percentages of interferon-gamma(IFNgamma)-secreting OT-1T cells in mice that received combined therapy to levels similar to those of control mice. These data suggest that even relatively low levels of gene transfer of suicide genes into tumors may have therapeutic value as an adjuvant for other T-cell therapies, by providing immunological signals that support T-cell activation and expansion in vivo.

Milk versus medicine for the treatment of iron deficiency anaemia in hospitalised infants.

AIMS: To compare iron fortified follow-on milk (iron follow-on), iron fortified partially modified cows' milk (iron milk), and iron medicine for the treatment of iron deficiency anaemia (IDA) in hospitalised infants. METHODS: In a randomised controlled trial, infants aged 9-23 months with IDA and who were hospitalised with an acute illness received iron follow-on (12 mg/l ferrous iron), iron milk (12.9 mg/l ferrous iron), or iron medicine (ferrous gluconate at 3 mg/kg of elemental iron once daily). All interventions were given for three months. Changes in measures of iron status three months after hospital discharge were determined. RESULTS: A total of 234 infants were randomised. Iron status was measured at follow up in 59 (70%) iron medicine, 49 (66%) iron follow-on, and 54 (70%) iron milk treated infants. There was a significant (mean, 95% CI) increase in haemoglobin (15 g/l, 13 to 16) and iron saturation (9%, 8 to 10) and decrease in ferritin (-53 microg/l, -74 to -31) in all three groups. Mean cell volume increased in iron follow-on (2 fl, 1 to 3) and iron milk (1 fl, 0.1 to 3) treated infants, but not in the iron medicine group (1 fl, -1 to 2). The proportion with IDA decreased in all three groups: iron medicine 93% to 7%, iron follow-on 83% to 8%, and iron milk 96% to 30%. Adverse effects, primarily gastrointestinal, occurred in 23% of the iron medicine, 14% of the iron follow-on, and 13% of the iron milk group. CONCLUSIONS: Iron fortified follow-on milk, iron fortified partially modified cows' milk, and iron medicine all effectively treat IDA in infancy.

Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age.

BACKGROUND: The prevalence of atopic dermatitis (AD) is increasing in Western societies. The hygiene hypothesis proposes that this is due to reduced exposure to environmental allergens and infections during early life. OBJECTIVES: To examine factors associated with a diagnosis of AD at 3.5 years of age, especially those factors implicated by the hygiene hypothesis. METHODS: The Auckland Birthweight Collaborative study is a case-control study of risk factors for small for gestational age babies. Cases were born at term with birthweight < or = 10th centile; controls were appropriate for gestational age, with birthweight > 10th centile. The infants were assessed at birth, 1 year and 3.5 years of age. Data were collected by parental interview and examination of the child. AD was defined as the presence of an itchy rash in the past 12 months with three or more of the following: history of flexural involvement; history of generally dry skin; history of atopic disease in parents or siblings; and visible flexural dermatitis as per photographic protocol. Statistical analyses took into account the disproportionate sampling of the study population. RESULTS: Analysis was restricted to European subjects. Eight hundred and seventy-one children were enrolled at birth, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children seen at 3.5 years. The prevalence of AD did not differ by birthweight. AD at 3.5 years was associated with raised serum IgE > 200 kU L(-1), and wheezing, asthma, rash or eczema at 1 year. In multivariate analysis, adjusted for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents: maternal atopy only, adjusted odds ratio (OR) 3.83, 95% confidence interval (CI) 1.20-12.23; paternal atopy only, adjusted OR 3.59, 95% CI 1.09-11.75; both parents atopic, adjusted OR 6.12, 95% CI 2.02-18.50. There was a higher risk of AD with longer duration of breastfeeding: < 6 months, adjusted OR 6.13, 95% CI 1.45-25.86; > or = 6 months, adjusted OR 9.70, 95% CI 2.47-38.15 compared with never breastfed. These findings remained significant after adjusting for environmental factors and a personal history of atopy. AD at 3.5 years was associated with owning a cat at 3.5 years (adjusted OR 0.45, 95% CI 0.21-0.97) but not with owning a dog at 3.5 years, pets at 1 year, nor with older siblings. Furthermore, AD at 3.5 years was not associated with gender, socioeconomic status, maternal smoking, parity, damp, mould, immunizations, body mass index or antibiotic use in first year of life. CONCLUSIONS: A personal and a parental history of atopic disease are risk factors for AD at 3.5 years. Duration of breastfeeding was associated with an increased risk of AD. No association was found with those factors implicated by the hygiene hypothesis. This study suggests that breastfeeding should not be recommended for the prevention of AD.

Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma.

BACKGROUND: Cigarette smokers with asthma are insensitive to short term inhaled corticosteroid therapy, but efficacy when given for a longer duration at different doses is unknown. METHODS: Ninety five individuals with mild asthma were recruited to a multicentre, randomised, double blind, parallel group study comparing inhaled beclomethasone in doses of 400 microg or 2000 microg daily for 12 weeks in smokers and non-smokers. The primary end point was the change in morning peak expiratory flow (PEF). Secondary end points included evening PEF, use of reliever inhaler, number of asthma exacerbations, spirometric parameters, and asthma control score. RESULTS: After 12 weeks of inhaled beclomethasone there was a considerable difference between the morning PEF measurements of smokers and non-smokers with asthma (-18 (95% CI -35 to -1), adjusted p = 0.035). Among those receiving 400 microg daily there was a difference between the mean (95% CI) morning PEF (l/min) in smokers and non-smokers (-25 (95% CI -45 to -4), adjusted p = 0.019) and in the number of asthma exacerbations (6 v 1 in smokers and non-smokers, respectively, p = 0.007). These differences were reduced between smokers and non-smokers receiving 2000 microg inhaled beclomethasone daily. CONCLUSIONS: Compared with non-smokers, smokers with mild persistent asthma are insensitive to the therapeutic effect of low dose inhaled corticosteroid treatment administered for a 12 week period. The disparity of the response between smokers and non-smokers appears to be reduced with high dose inhaled corticosteroid. These findings have important implications for the management of individuals with mild asthma who smoke.

Maternal nutritional risk factors for small for gestational age babies in a developed country: a case-control study.

AIMS: To assess the effect of maternal diet during pregnancy on the risk of delivering a baby who is small for gestational age (SGA). METHODS: Case-control study of 844 cases (SGA) and 870 controls (appropriate size for gestational age (AGA)). Only term (37+ completed weeks of gestation) infants were included. Retrospective food frequency questionnaires were completed at birth on the diet at the time of conception and in the last month of pregnancy. RESULTS: At the time of conception, mothers of AGA infants ate significantly more servings of carbohydrate rich food and fruit, and were more likely to have taken folate and vitamin supplements than mothers of SGA infants. There was some evidence that mothers of AGA infants also ate more servings of dairy products, meat, and fish (0.05 < p < 0.1). However, after adjustment for maternal ethnicity, smoking, height, weight, hypertension, and occupation, fish intake (p = 0.04), carbohydrate-rich foods (p = 0.04), and folate supplementation (p = 0.02) were associated with a reduced risk of SGA. In the last month of pregnancy, only iron supplementation was associated with a reduced risk of SGA (p = 0.05) after adjustment for potential confounders. CONCLUSIONS: This study suggests that small variations in maternal diets within the normal range during pregnancy in developed countries are associated with differences in birth weight.

Real-time breath monitoring of propofol and its volatile metabolites during surgery using a novel mass spectrometric technique: a feasibility study.

BACKGROUND: At present, there is no rapid method for determining the plasma concentration of i.v. anaesthetics. A solution might be the measurement of the anaesthetic concentration in expired breath and its relation to the plasma concentration. We used chemical ionization methods to determine whether an i.v. anaesthetic can be detected in the low concentrations (parts per billion by volume) in the expired breath of an anaesthetized patient. METHOD: Chemical ionization mass spectrometry can measure trace gases in air with high sensitivity without interference from major gases. We carried out a feasibility trial with a proton transfer reaction mass spectrometer (PTR-MS) to monitor the i.v. anaesthetic agent propofol and two of its metabolites in exhaled gas from an anaesthetic circuit. Exhaled gas was sampled via a 4 m long, unheated tube connected to the PTR-MS. RESULTS: Propofol and its metabolites were monitored in real time in the expired breath of patients undergoing surgery. CONCLUSION: Routine measurement of i.v. agents, analogous to that for volatile anaesthetic agents, may be possible.

L-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro.

BACKGROUND: Topical phenylephrine has been shown to increase resting anal canal pressure in normal and incontinent individuals. However, high concentrations of gel (10-40 per cent) are required that may cause local side-effects. The aim of this study was to determine whether methoxamine, another alpha-1-adrenoceptor agonist, might be a more potent alternative to phenylephrine. METHODS: Porcine internal anal sphincter (IAS) tissue was cut into strips, suspended in a superfusion organ bath and allowed to equilibrate. Strips were subjected to each drug under test for 20 s, sufficient to obtain stable tone. Phenylephrine, methoxamine (1 : 1 : 1 : 1 ratio of its four isomers) and each of the individual isomers of methoxamine were evaluated in turn. RESULTS: In vitro, methoxamine racemate and phenylephrine were similarly potent in causing contraction of IAS strips (mean(s.e.m.) dose giving half maximal effect (EC(50)) at 74.7(16.5) versus 58.3(13.4) micro M respectively; P = 0.443). However, one of the methoxamine isomers, L-erythro-methoxamine (EC(50) 17.6(3.7) micro M), was significantly more potent than the other three isomers, methoxamine racemate and phenylephrine (P = 0.002). CONCLUSION: L-Erythro-methoxamine is four times more potent than phenylephrine and is a possible treatment for incontinence. Trials are under way to examine the efficacy of L-erythro-methoxamine in vivo.

Snoring in the first year of life.

AIM: To describe the prevalence of snoring in infancy and the factors associated with snoring. METHODS: The investigation comprised a cross-sectional study of 1800 infants. Snoring was ascertained by interviewer-administered questionnaire. RESULTS: The prevalence of snoring was 15.8% in the first 4 wk of life and 26.1% in the past 2 wk. Snoring in the past 2 wk was associated with increasing age of the infant, male gender, maternal smoking, sleep position, number of respiratory infections and snoring in the first 4 wk of life after adjustment for potential confounders. No associations were found with snoring in the first 4 wk of life. CONCLUSION: Snoring is common in infancy. The identified risk factors for snoring are probably causally related to snoring. Further studies are needed to establish whether snoring in infancy is associated with current or subsequent morbidity.