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The burgeoning commitment to contracting the delivery of bus services through competitive tendering or negotiated performance-based contracts has been accompanied by as many contract payments schemes as there are contracts. We are now well placed to design a simplified performance-linked payment (SPLP) model that can be used as a reference point to ensure value for money, given the accumulation of experiences throughout the world which have revealed substantive common elements in contracts. Whether the payment to the operator is framed as a payment per passenger or as a payment per service kilometre, the SPLP identifies efficient subsidy outcomes that are linked to a proxy indicator of net social benefit per dollar of subsidy. We illustrate how the SPLP model can be applied to obtain the gross (subsidy) cost per passenger (or per passenger km) from measures of gross cost efficiency and network effectiveness. This model can then be used as part of a benchmarking activity to identify reference value of money prospects in respect of passengers per $ subsidy outlay by adjusting for influences not under the control of the service provider. A single framework to identify contract payments to operators, and to assess (i.e., benchmark) operator performance on critical KPIs, is provided by internalising critical key performance indicators (KPIs) in the design of the SPLP. The proposed SPLP model is sufficiently general to be independent of the procurement method (competitive tendered or negotiated, for example) and of the treatment of revenue allocation (net or gross based contracts), with the additional advantage of being able to assess value for money for government.

The motivation of the project was to investigate the use of oxygen-challenge magnetic resonance imaging (OC-MRI) as a method of diagnosing foetal growth restriction. Foetal growth restriction is associated with restricted foetal oxygen supply and is also associated with increased risks of perinatal mortality and morbidity, and a number of serious and chronic health problems. Measurements of T2* relaxation time, an MRI parameter which increases with blood oxygenation, were made in the right lobe of the foetal liver in 80 singleton pregnancies, before and after the mother breathed oxygen. The groups consisted of 41 foetuses with normal growth and 39 with apparent growth restriction. The mean +/- SD gestational age at scanning was 35 +/- 3 weeks. Changes in foetal liver T2* on maternal oxygen breathing showed no significant difference between the groups therefore the OC-MRI protocol used in this study has no value in the diagnosis of foetal growth restriction. A secondary finding was that a significant positive correlation of T2* change with gestational age was observed. Future studies on the use of oxygen-challenge MRI to investigate foetal growth restriction may therefore need to control for gestational age at the time of MR scanning in order to observe any underlying foetal growth-related effects.

Exercise-induced oxidative stress is investigated as a potential performance-limiting factor in human sports medicine. Therefore, the present study aimed to assess whether physiological variables that change with exercise intensity were correlated with blood oxidant markers in healthy and heaves-affected horses. Seven healthy horses, 8 heaves-affected in remission and 7 heaves-affected in crisis performed a standardised exercise test (SET) of stepwise increasing intensity. Variables monitored during exercise were heart rate (HR), venous plasma lactate (LA), packed cell volume (PCV) and arterial oxygen tension (PaO2). Oxidant markers (uric acid [UA], 8-iso-PGF2alpha and reduced [GSH] and oxidised glutathione [GSSG]) were analysed in venous peripheral blood sampled at rest (R), at peak-exercise intensity (Emax), 15 (E15) and 60 (E60) min after SET. There was a significant effect of heaves on oxidant markers and, therefore, correlation analyses between physiological variables and oxidant markers were performed separately per horse group. In healthy horses, UA analysed at Emax was positively correlated with LA. Furthermore, GSH analysed at Emax and E15 was positively correlated with PaO2. In healthy and heaves-affected horses in remission, GSH and GSSG determined at Emax were negatively correlated with HR. There was no significant correlation between 8-iso-PGF2alpha and physiological variables. In conclusion, a correlation between the physiological response to exercise and some oxidant markers exists in healthy horses. However, in heaves-affected horses the blood oxidant status is probably more dependant on airway disease than on exercise. Future studies should be undertaken to assess whether antioxidant supplementation might positively influence the oxidant-antiodidant balance in exercising horses.

Summary Reasons for performing study: Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. Objectives: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. Methods: Seven healthy control horses and 7 RAO-affected horses were exposed to 0.8 ppm ozone for 2 h at rest. Results: At baseline, bronchoalveolar lavage fluid (BALF) ascorbic acid concentrations were lower in RAO-affected horses than healthy controls. Ozone appeared to preferentially oxidise glutathione rather than ascorbic acid 6 h after exposure. Individual healthy and RAO-affected horses demonstrated oxidation of BALF glutathione after ozone exposure. Overall, RAO-affected horses did not demonstrate increased oxidative stress following ozone exposure, compared with healthy horses. Ozone did not induce significant airway inflammation in either group. Conclusions: RAO-affected horses in remission are not more sensitive to ozone despite a decreased pulmonary antioxidant capacity. Sensitivity to ozone appears to be independent of initial pulmonary antioxidant status. Potential relevance: Horses with high susceptibility to oxidative stress may benefit from antioxidant supplementation.

Studies investigating the role of oxidative stress in both the ageing process and osteoarthritis (OA) in human beings are limited by the unavailability of samples from healthy subjects. OA occurs naturally in the horse and has been used as a model of human OA. The objective of this study was to determine the effect of ageing and OA on the non-enzymatic synovial fluid antioxidant status of the horse. The concentrations of ascorbic acid, dehydroascorbate (DHA, oxidized ascorbic acid), uric acid, glutathione, α-tocopherol and thiobarbituric acid reactive substances (TBARS) were determined in paired synovial fluid and plasma samples from 25 horses aged between 3 and 25 years. Osteoarthritic lesions were scored from 0 (healthy) to 4 (severe OA). Glutathione was not detectable in synovial fluid. Neither plasma nor synovial fluid antioxidant concentrations were affected by age. Ascorbic acid concentrations in plasma correlated strongly with those in synovial fluid from both healthy ( P P = 0.003). Synovial fluid concentrations of ascorbic acid and uric acid were not influenced by OA compared with healthy joints. However, the concentration of DHA was slightly, but significantly, elevated in synovial fluid from joints with severe OA (95% CI: [2.2, 11.8] μmol l − 1 ; P

Manual vacuum aspiration (MVA) is an alternative to the standard surgical curettage, performed under local anaesthetic in the setting of a treatment room. The aim of our study was to assess the efficacy of MVA in the management of first trimester early fetal demise and first- and mid-trimester incomplete miscarriage. This was a retrospective study of 246 patients who were scheduled to undergo MVA for first trimester early fetal demise and first- and mid-trimester incomplete miscarriage. One woman was excluded in the analysis because of the procedure being abandoned prior to MVA. Efficacy of the procedure was 94.7% (232/245). Incomplete uterine evacuation was seen in 5.3% (13/245) patients. Although not widely used in the UK, MVA could be considered routinely, thus avoiding general anaesthesia and the need for access to theatre.

Dean JCS, Gray ES, Stewart KN, Brown T, Lloyd DJ, Smith NC, Pope FM. Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression. Clin Genet 1993: 44: 287–291. © Munksgaard, 1993 Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha-1 and alpha-2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.

The aim of this study was to test the hypothesis that pulmonary inflammation and emphysema induced by cadmium (Cd) inhalation are associated with pulmonary oxidative stress. Two groups of Sprague Dawley rats were used: one vehicle-exposed group undergoing inhalation of NaCl (0.9%, n = 24) and one Cd-exposed group undergoing inhalation of CdCl(2) (0.1%, n = 24). The animals in the vehicle-and Cd-exposed groups were divided into 4 subgroups (n = 6 per group), which underwent either a single exposure (D2) of 1H or repeated exposures 3 times/week for 1H for a period of 3 weeks (3W), 5 weeks (5W) or 5 weeks followed by 2 weeks without exposure (5W + 2). At sacrifice, the left lung was fixed for histomorphometric analysis (median inter-wall distance, MIWD), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. Cytological analysis of BALF was performed and BALF was analysed for oxidant markers 8-iso-PGF(2a), uric acid (UA), reduced (AA) and oxidised ascorbic acid (DHA) and reduced (GSH) and oxidised glutathione (GSSG). Cd-exposure induced a significant increase of BALF macrophages and neutrophils. 8-iso-PGF(2a), UA, GSH and GSSG were significantly increased at D2. At 5W and 5W + 2, AA and GSH were significantly lower in Cd-exposed rats, indicating antioxidant depletion. MIWD significantly increased in all repeatedly Cd-exposed groups, suggesting development of pulmonary emphysema. 8-iso-PGF(2a) and UA were positively correlated with macrophage and neutrophil counts. GSH, GSSG and 8-iso-PGF(2a) were negatively correlated with MIWD, indicating that Cd-induced emphysema could be associated with pulmonary oxidative stress.

Diminished basal plasma cortisol concentrations and a blunted cortisol response to exercise have been observed in human asthmatics. In horses with recurrent airway obstruction (RAO), plasma concentrations of cortisol at rest are not significantly different from those of healthy horses, but the effect of exercise on endogenous cortisol concentrations has not been described. Ascorbic acid is a non-enzymatic antioxidant with proposed immune-modulating properties. In man, supplementation with ascorbic acid has been shown to attenuate the exercise-induced increase in plasma cortisol following prolonged, submaximal exercise. The relationship between cortisol and ascorbic acid has not previously been investigated in the horse. In a blinded cross-over design, five horses with RAO and six healthy non-RAO controls performed a standard exercise test following 4 weeks of supplementation with either an antioxidant (providing 10 mg ascorbic acid kg−1day−1) or a placebo (−1day−1). Venous blood samples were obtained 1 h prior to exercise and at 0, 15, 60 min and 24 h thereafter. Exercise resulted in a significant increase in plasma cortisol concentrations in both groups of horses (P−1, respectively) were not significantly different from those in the non-RAO group (129±43 and 218±30 μmol l−1, respectively). Antioxidant supplementation increased basal and post-exercise concentrations of plasma ascorbic acid in RAO and non-RAO horses (P−1, post-exercise 222±21 μmol l−1; non-RAO: rest 140±11 μmol l−1, post-exercise 227±35 μmol l−1). In conclusion, RAO-affected horses in remission demonstrate the same cortisol response to exercise as healthy controls. Antioxidant supplementation had no impact on post-exercise concentrations of plasma cortisol in either healthy or RAO-affected horses in remission.

A review of physiology and behaviour–based studies on the function of stereotypic behaviour indicates contradiction and inconsistency within the literature. By considering appropriate neurochemical data alongside an existing model of motivation (Hughes and Duncan, 1988), a greater understanding of the function of stereotypy may be gained. The Hughes and Duncan model (1988), described stereotypies as highly motivated appetitive behaviours performed repeatedly in an environment where consummatory goals are denied. Moreover, appetitive behaviours activate reward circuitry such as the ventral tegmental area and nucleus accumbens and are thus considered to have a reward value associated with their performance (Carr, 2002; Jones et al., 1990). Stress induced sensitisation of reward circuitry may result in appetitive ‘stereotypies’ having increased reward value, perhaps becoming consummatory in their own right. In such a scenario, stereotypic behaviour could function as a coping tool, allowing the animal to counter the effects of an aversive environment.

Vitamin C (ascorbic acid) is a non-enzymatic antioxidant important in protecting the lung against oxidative damage and is decreased in lung lining fluid of horses with airway inflammation. To examine possible therapeutic regimens in a species with ascorbate-synthesising capacity, we studied the effects of oral supplementation of two forms of ascorbic acid, (each equivalent to 20 mg ascorbic acid per kg body weight) on the pulmonary and systemic antioxidant status of six healthy ponies in a 3 x 3 Latin square design. Two weeks supplementation with ascorbyl palmitate significantly increased mean plasma ascorbic acid concentrations compared to control (29 +/- 5 and 18 +/- 7 micromol/l, respectively; p0.05). Calcium ascorbyl-2-monophosphate, a more stable form of ascorbic acid, also increased mean plasma ascorbic acid concentrations, but not significantly (23 +/- 1 micromol/l; p = 0.07). The concentration of ascorbic acid in bronchoalveolar lavage fluid increased in five out of six ponies following supplementation with either ascorbyl palmitate or calcium ascorbyl-2-monophosphate compared with control (30 +/- 10, 25 +/- 4 and 18 +/- 8 micromol/l, respectively; p0.01). Neither supplement altered the concentration of glutathione, uric acid or alpha-tocopherol in plasma or bronchoalveolar lavage fluid. In conclusion, the concentration of lung lining fluid ascorbic acid is increased following ascorbic acid supplementation (20 mg/kg body weight) in an ascorbate-synthesising species.

Objective To assess the efficacy and safety of mifepristone in combination with misoprostol in the management of late fetal death. Design Observational study. Setting Aberdeen Maternity Hospital, Aberdeen. Methods A consecutive series of 96 women with intrauterine death after 24 weeks of gestation were studied. Each woman received a single dose of 200mg mifepristone orally, following which a 24–48 hour interval was recommended before administration of misoprostol. For gestations of 24–34 weeks, 200μg of intravaginal misoprostol was administered, followed by four oral doses of 200μg at three hourly intervals. Gestations over 34 weeks were given a similar regimen but a reduced dose of 100μg misoprostol. Results The average induction to delivery interval was 8.5 hours. Ninety-five women (98.9%) were delivered within 72 hours of administration of first dose of misoprostol, with 66.7%, 87.5%, 92.7% and 95.8% women delivering within 12, 24, 36 and 48 hours, respectively. No significant correlation was found between mean induction to delivery interval and maternal age, parity, Bishop's score, birthweight and mifepristone/misoprostol interval. The induction to delivery interval was shorter with increasing gestation (P = 0.04). Mild side effects were noted in eight (8.3%) women. Three (3.1%) women had treatment for presumed or proven pelvic sepsis. No cases of uterine tachysystole, haemorrhage or coagulopathy were recorded. Conclusion The combination of mifepristone and misoprostol for induction of labour following late fetal death is an effective and safe regimen. The induction to delivery interval with this regimen appears shorter than studies using mifepristone or misoprostol.

Helen Atterby, Neil Smith, Qasim Chaudhry and David Stead of he Central Science Laboratory (Department for Environment, Food and Rural Affairs) based in York, UK, describe the ways in which plants and microbes can be used in remediation processes

BACKGROUND: This study aims to assess the efficacy of a combination of mifepristone and misoprostol in the management of missed miscarriage and anembryonic pregnancy. METHODS: Data of 220 consecutive women with miscarriage, undergoing medical evacuation of the uterus were collected prospectively at an early pregnancy assessment unit in a tertiary referral hospital. Each woman received a single oral dose of mifepristone 200 mg and 36–48 h later vaginal misoprostol 800 µg. Three hours following the first dose, two further doses of misoprostol, 400 µg each, were administered vaginally or orally at 3 h intervals. Women who failed to pass products of conception were offered repeat medical regime with misoprostol. Success was defined as complete uterine evacuation within 3 days, without the need for surgical evacuation. RESULTS: The overall success rate of medical management was 84.1%. Mifepristone alone induced natural expulsion of products of conception in 18.1% of women. The median dose of misoprostol required was 1600 µg and the median induction miscarriage interval after first prostaglandin administration was 8.04 h (range: 0.58–50.54 h). Of the 142 women who were symptomatic at presentation the medical regime failed in 30 (21.1%), compared with five (6.4%) failures of the 78 who were asymptomatic (P 0.007). Of the 35 women who had surgical evacuation, eight required an emergency curettage for bleeding. CONCLUSIONS: The combination of oral mifepristone 200 mg with vaginal or oral misoprostol is an alternative to surgical management of early fetal demise, although it is not as effective as surgery.

Nonphyseal supracondylar fractures of the femur are considered to be uncommon in children and have received little attention in the literature. A retrospective review of femoral fractures in children at the authors' institution was undertaken to ascertain the incidence of supracondylar femoral fractures, the influence of associated musculoskeletal conditions, and pitfalls of management. In this study of 102 femoral fractures, there was an incidence of 12% of supracondylar fractures. Four of 12 patients had a significant predisposing musculoskeletal condition contributing to the genesis of the fracture. Five fractures were undisplaced and easily managed. Seven displaced fractures required intervention to achieve an adequate reduction. The literature is reviewed and a classification system for these fractures is presented. Treatment options are discussed and recommendations made based on this experience.

Repetitive sequence-derived PCR using the BOX-A1R primer was used to generate genomic fingerprints of Clavibacter michiganensis subspecies sepedonicus, the causal agent of bacterial ring rot disease of potato. A total of 35 C. michiganensis subsp. sepedonicus strains were selected for study in order to represent the widest possible historical, morphological and geographical diversity of the organism. Comparison was made with genomic fingerprints of C. michiganensis subsp. michiganensis, C. michiganensis subsp. insidiosus, C. michiganensis subsp. tessellarius, C. michiganensis subsp. nebraskensis as well as other related Gram positive plant pathogens. The resultant genomic fingerprints and subsequent cluster analysis show C. michiganensis subsp. sepedonicus to form a remarkably homogeneous group with approximately 84% similarity between all of the strains tested. There was no evidence to suggest that fingerprints varied with historic, morphological or geographic diversity. In addition, C. michiganensis subsp. sepedonicus isolated from asymptomatic sugar beet had the same fingerprint as those which were isolated as potato pathogens. This group was easily distinguished from the clusters formed by the other subspecies of C. michiganensis and Gram positive plant pathogens. The potential for this technique to be used as a relatively rapid method to replace the time consuming and sometimes inconclusive eggplant bioassay test is discussed.

Although it has been observed that the incidence of preeclampsia is lower among women having their second pregnancy than among women having their first, it is unclear whether protection against preeclampsia results from parity or gravidity. For example, 1 previous study reported a protective effect in the second pregnancy of a late miscarriage in the first pregnancy, whereas other studies have found that only deliveries >37 completed weeks have a protective effect. Another study showed that a previous abortion, either spontaneous or therapeutic, was protective, irrespective of gestational age. This retrospective observational study was designed to determine whether the reduced risk of preeclampsia in the second pregnancy is dependent or independent of the first pregnancy's outcome, including the gestational age at delivery. Data from 24,500 women with first and second pregnancies between 1986 and 2006 were obtained from the Aberdeen Maternity and Neonatal Databank in Scotland. The treatment group included all women who developed preeclampsia in their second pregnancy, whereas the control group included all women with normotensive second pregnancies. Potential independent risk factors for the development of preeclampsia in the second pregnancy were evaluated, and crude and adjusted odds ratios (OR) were estimated using binary logistic regression. A total of 903 (3.7%) of the 24,500 women in the study population had preeclampsia in the second pregnancy. Of these, 167 had a previous history of preeclampsia, for a recurrence rate of 14.2%. The incidence of preeclampsia was increased in women with interpregnancy intervals of 6 years or more (19.3% vs. 14.7%) and in those with an increase in BMI (70.8% vs. 63.2%), whereas a change of partner appeared to have a protective effect (3.5% vs. 5.6%). Compared to women who were normotensive in the first pregnancy, women with a history of preeclampsia in the previous pregnancy had an adjusted odds ratio of 5.12 (95% confidence interval [CI] of 4.42–6.48) for developing preeclampsia in the second pregnancy. Using a model that included only live births, and after controlling for maternal age, BMI, smoking, change of partner, interpregnancy interval, and previous history of preeclampsia or gestational hypertension, the risk of preeclampsia in the second pregnancy appeared to decrease with increasing gestational age at delivery of the first pregnancy. Compared to women who had a previous term delivery, the odds ratio for developing preeclampsia in the second pregnancy was 4.22 (95% CI, 2.54–7.03) for women whose previous pregnancy ended in the second trimester, 2.32 (95% CI, 1.62–3.32) for women who had a previous preterm birth at 25 to 32 weeks', and 1.62 (95% CI, 1.46–1.72) for those with a previous preterm birth at 33 to 36 weeks'. The effect of a previous fetal death was evaluated using a second model that included all study patients whose previous pregnancy extended beyond 20 weeks. After adjusting for the same variables listed above, the risk of preeclampsia was the same for women with a previous history of stillbirth as for those with a previous live birth. Only first deliveries beyond 37 weeks were protective against preeclampsia, independent of outcome, in the second pregnancy. These findings suggest that the protective effect of a previous pregnancy against preeclampsia in the second pregnancy is dependent on the gestational age at delivery of the first pregnancy but not on that pregnancy's outcome.

Summary Pulmonary function tests, bronchoalveolar lavages, and venous blood samplings were performed 24 hours before and one hour after a standardized strenous treadmill exercise test on six horses suffering from chronic obstructive pulmonary disease (COPD) in clinical remission. Pulmonary function test consisted of the measurement of the mechanics of breathing and arterial blood gases analyses. During the exercise tests, heart and respiratory rates, and venous plasma lactate, pH and packed cell volume were controlled. Venous blood was analyzed for some markers of the oxidative stress, i.e., hemolysate glutathione redox ratio and oxidized glutathione, and plasma uric acid. BAL was analyzed for cell cytology as well as for markers of oxidative stress, i.e., glutathione redox ratio, and isoprostanes concentration. The procedure was repeated twice, i.e., before and after two IV injections of 40mg hyaluronate administered at seven day intervals. The results were compared to assess a possible influence of the treatment on the pulmonary and systemic inflammatory and/or oxidative status of these horses. Hyaluronate did not influence the pulmonary function test or the physiological parameters recorded during exercise. There was a decrease in the percentage of BAL neutrophils after the treatment, suggesting a possible anti-inflammatory effect at the pulmonary level. As well, the concentration of isoprostanes in the pulmonary epithelium lining fluid was significantly lower after the treatment, which might be either a consequence of the decrease of the BAL neutrophils, or related to a possible antioxidant effect of the treatment. Lastly, the exercise-induced increase in plasma uric acid was significantly less marked after the treatment, which could be due to a systemic antioxidant effect of the hyaluronate. In conclusion, this preliminary study brings some evidence that hyaluronate could have some antiinflammatory and antioxidant effects at the pulmonary—and systemic—level in COPD horses in remission. However, it does not help to understand the possible mechanisms underlying these observations. Further studies are now necessary to better understand its action, to assess the effect of the product on the pulmonary function of horses suffering from other respiratory problems as well as to assess the efficiency of other ways of administration, i.e., nebulization.

The effect of nitric oxide synthase (NOS) inhibition during exercise on lactate production was investigated in five Thoroughbred horses. A standard exercise test (SET), consisting of three canters (approximately 55 per cent VO2max), with walking and trotting between each canter, was performed twice (control and test, in random order) by each horse. Nphi-nitro-L-arginine methyl ester (L-NAME; 20 mg kg-1), a competitive inhibitor of NOS, induced a significant increase (P0.05) in plasma lactate [5.7 (2.9) vs 11.8 (3.8) mmol L-1], which continued to increase despite administration of L-arginine, the substrate for NOS. There were no differences in cardiac output (Q) or the total body oxygen consumption (VO) between each SET. The results show that non-specific inhibition of NOS isoforms during exercise in the horse increases plasma lactate concentration, although the mechanism/s remain uncertain.

Summary To test whether isoprostanes could be used as markers of oxidative stress in horses, their concentration was determined in plasma and in pulmonary epithelial lining fluid (PELF) in 3 models of oxidative stress: (1) strenuous exercise, (2) acute COPD crisis and (3) exercise combined with COPD crisis. Four horses were investigated twice, once in crisis and once in remission. The animals underwent a standardised treadmill exercise test. Isoprostane assessment was performed in plasma and bronchoalveolar lavage fluid 24 h before and 1 h after exercise and in plasma also immediately after exercise. Exercise in remission induced a significant increase of isoprostanes in plasma and in PELF. In horses in crisis, the isoprostane concentrations did not increase in plasma, while they did increase in PELF. Lastly, exercise in crisis increased plasma levels of isoprostanes, but did not change PELF isoprostanes. In conclusion, 1) isoprostanes are increased by systemic oxidative stress induced by strenuous exercise in COPD horses in remission either in PELF or in plasma; 2) only PELF and not plasma isoprostanes are increased by pulmonary oxidative stress induced by COPD crisis and 3) unexpectedly, exercise in crisis increased plasma but not PELF isoprostanes.

1. The effects of exercise on the production rate of nitric oxide (NO) in exhaled air (VNO) and the effects of inhaled NO (80 p.p.m.) on cardiovascular and respiratory parameters were investigated in five Throughbred horses. 2. The concentration of NO ([NO]) in exhaled air collected from within the nasal opening was lower when collected at a high flow rate of 80 l min-1 than at a low flow rate of 20 l min-1: when trotting at 3.7 m s-1 the values were 0.78 +/- 0.15 and 1.23 +/- 9.14 p.p.b., respectively, and when cantering at 9 m s-1 the values were 1.69 +/- 0.31 and 2.25 +/- 0.32 p.p.b., respectively. 3. Nebulized methoxamine (40 mg ml-1 for 60 s), an alpha 1-adrenergic agonist, further reduced [NO] during the 9 m s-1 canter to 1.05 +/- 0.14 and 1.99 +/- 0.41 p.p.b. when collected at 80 and 20 l min-1, respectively, and induced cyclical changes in the breathing pattern. 4. Exercise induced a linear increase in VNO with work intensity to a maximum (428.1 +/- 31.6 pmol min-1 kg-1) which coincided with the maximal oxygen uptake for the horses (138.3 +/- 11.7 ml min-1 kg-1), although a further increase in VNO (779.3 +/- 38.4 pmol min-1 kg-1) occurred immediately after exercise. The changes in VNO correlated well with the tidal volume (r = 0.968; P < 0.01) and the haematocrit (r = 0.855; P < 0.01). 5. In the first 2 min of high intensity exercise, inhaled NO (80 p.p.m.) significantly (P < 0.05) reduced the pulmonary artery pressure: during the first minute, pulmonary artery pressure was 83.1 +/- 7.6 mmHg compared with a control value of 94.4 +/- 6.3 mmHg, and during the second minute, 84.2 +/- 7.1 mmHg compared with a control value of 98.4 +/- 4.7 mmHg. There were no other significant changes in cardiovascular or respiratory indices, including cardiac output, measured during exercise between control and inhaled NO tests. 6. The results show that exhaled NO is released from the airways of the horse and may contribute to the regulation of pulmonary vascular tone during exercise.

The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e-25.141+ 159.93e-10.96tfor allopurinol and Cp = 321.09e-972t+ 82.39e-0.44tfor oxypurinol. Allopurinol was rapidly removed from the plasma, compared to oxypurinol, with an elimination half-life (t1/2β) of 0.09 h and an area under the curve (AUC) of 19.8 μmol·h/L after intravenous administration, while the t1/2β and AUC of oxypurinol were 1.09 h and 231 μmol·h/L, respectively. The bioavailability of allopurinol was low (14.3%), although no allopurinol was detected in the plasma of two horses after oral administration. However, the AUC of drug and metabolite after intravenous administration of allopurinol was equivalent to that of intravenously injected oxypurinol. The results suggest that allopurinol is rapidly metabolised in vivo and that the majority of the pharmacological activity of allopurinol in the horse may result from the action of the active metabolite, oxypurinol.

A change in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) can be used to indicate oxidative stress in vivo. A rapid and highly sensitive isocratic reversed-phase high-performance liquid chromatographic method using coulometric electrochemical detection (LCEC) has been developed to simultaneously detect GSH and GSSG in equine biological fluids. Perchloric acid was used to extract GSH and GSSG from equine plasma and haemolysates, and methanol was used to deproteinise bronchoalveolar lavage fluid samples. Injection of extracts onto a Hypersil ODS HPLC column produced well resolved peaks corresponding to GSH and GSSG. The concentrations of GSH and GSSG found in equine haemolysates were similar to those previously found in humans and laboratory animals, although, to the authors' knowledge, previous attempts to measure GSH and GSSG in bronchoalveolar lavage fluid using LCEC have been unsuccessful. This method can be used to measure the GSH redox ratio in biological fluids during physiological conditions that may induce oxidative stress, such as exercise and disease.

A prospective randomized parallel-group study was carried out to compare the efficacy of a single dose vaginal prostaglandin E2 gel with forewater amniotomy for induction of labour at term in 260 parturients (110 primigravid and 150 parous women) with low risk pregnancy and favourable cervix. In the prostaglandin E2 (PGE2) managed group, the primigravidae were treated with 2 mg PGE2 gel and parous patients with 1 mg PGE2 gel. Forewater amniotomy was performed 4 h later, or sooner if women requested analgesia. In the amniotomy group, artificial forewater amniotomy was carried out and a repeat cervical assessment done 4 h later, or sooner if women requested analgesia. In both groups, intravenous oxytocin was established if there was evidence of disordered uterine activity, 6 h after the start of initial intervention. An assessment of consumers' views was carried out by using a standardized questionnaire completed 48 h after delivery. There was a significant reduction in the requirement for oxytocin augmentation in women treated with PGE2: primigravidae, odds ratio (OR), 0.27 and 95% confidence interval (CI), 0.12-0.61; multiparae, OR, 0.19 and 95% CI, 0.08-0.45. Fewer primigravidae managed with PGE2 gel required epidural analgesia (OR, 0.16; 95% CI, 0.06-1.00). Fewer parous women managed with PGE2 gel required parenteral opiates (OR, 0.44; 95% CI, 0.23-0.85) and more women required inhalation analgesia or no analgesia (OR, 2.22; 95% CI, 1.76-2.79). The intervention to delivery intervals were shortened in PGE2 groups independent of parity but the differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Pneumonia caused by Panton–Valentine leukocidin-producing Staphylococcus aureus is associated with a high fatality rate. There have been few reported cases in HIV-1-co-infected patients. Here we report a fatal case of severe community-acquired pneumonia caused by Panton–Valentine leukocidin-producing S. aureus in a 45-year-old woman with HIV-2 infection.

Rationale Maternal smoking in pregnancy is associated with reduced birth weight and childhood lung function. This study determined when maternal smoking first influences fetal growth and how this relates to childhood respiratory outcomes. Methods A longitudinal cohort of 1924 pregnant women was recruited. Fetal ultrasound measurements at 11 weeks (crownerump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) and birth measurements were recorded. Childhood respiratory symptoms and spirometry were ascertained. Results Of the 1924 original study participants, fetal size was determined in 903 in the first trimester, 1544 in the second trimester and at term in 1737 infants. Maternal smoking when first pregnant was reported in 593 (31%) and was not associated with reduced CRL. There was an inverse exposure-response relationship between cigarette consumption and FL (mean reduction in lowest compared with highest tertile 0.91 cm, p¼0.033). Birth weight and length of those born to mothers who did (n¼331) and did not (n¼56) reduce cigarette consumption were similar and reduced compared with 186 infants whose mothers quit during the first trimester (p#0.020). Children of mothers who continued smoking had increased wheeze at age 2 years (OR 1.58, p¼0.017) and GP visits with wheeze at age 5 years (OR 2.18, p¼0.030) and mean reduction in forced expiratory volume in 1 s of 62 ml (p¼0.014) compared with controls. Conclusions Maternal smoking is associated with reduced fetal measurements in the second and third trimesters but not in the first trimester. Mothers who do not quit smoking during the first trimester deliver smaller infants who go on to have adverse respiratory outcomes in childhood.

Objective To compare conservative versus prostaglandin management of prelabour rupture of the membranes (PROM) in healthy primigravid women at term. Design A prospective randomized study. Setting Labour Ward, Aberdeen Maternity Hospital. Subjects 230 primigravidae at term with PROM, 115 allocated to be treated conservatively and 115 to be managed with prostaglandin treatment. Interventions In the conservatively managed group the women were observed for up to 24 h after hospital admission with PROM. The actively managed group had PGE2 gel (2 mg) instilled into the posterior fornix and if contractions had not commenced, a further dose of PGE2 gel (1 mg) was instilled 6 h later. In both groups, if labour had not established 24 h after admission, intravenous oxytocin was given in escalating doses. Main outcome measures PROM to delivery interval, oxytocin augmentation, mode of delivery, maternal and neonatal infective morbidity. Results There was a significant reduction in the PROM to delivery interval in the women managed actively with PGE2 gel and fewer women in the PGE2 group required oxytocin augmentation (31%vs 51%). The two managements groups were comparable for intrapartum analgesia, antibiotic treatment, babies requiring admission to the special care nursery unit and delivery by caesarean section. Conclusion The early use of prostaglandin is associated with a significant reduction in PROM to delivery interval without a significant increase in infective morbidity or caesarean section rate. However, the advantages of the conservative approach should not be overlooked. More work is still needed in the management of those women where uterine activity fails to establish within 24 h after PROM.

TaqMan polymerase chain reaction (PCR) exploits the 5′-nuclease activity of Taq DNA polymerase in conjunction with fluorogenic DNA probes. A positive PCR reaction results in a measurable emission of fluorescence within 2 h. TaqMan assays for several plant-pathogenic bacteria have been designed, including the potato brown rot pathogen Ralstonia solanacearum. Enrichment techniques designed to improve the detection of low pathogen populations in potato tissue are also suitable for use with TaqMan PCR. The quantitative aspect of TaqMan PCR enables relative population level differences between pre-enriched and enriched samples to be demonstrated and thus cell viability to be evaluated.

Manual vacuum aspiration (MVA) is an alternative to the standard surgical curettage, performed under local anaesthetic in the setting of a treatment room. The aim of our study was to assess the efficacy of MVA in the management of first trimester early fetal demise and first- and mid-trimester incomplete miscarriage. This was a retrospective study of 246 patients who were scheduled to undergo MVA for first trimester early fetal demise and first- and mid-trimester incomplete miscarriage. One woman was excluded in the analysis because of the procedure being abandoned prior to MVA. Efficacy of the procedure was 94.7% (232/245). Incomplete uterine evacuation was seen in 5.3% (13/245) patients. Although not widely used in the UK, MVA could be considered routinely, thus avoiding general anaesthesia and the need for access to theatre.

Objective To assess the effect of initial pregnancy outcome and gestational age on the risk of pre-eclampsia in the second pregnancy. Study design We conducted an observational study using routinely collected data from the Aberdeen Maternity and Neonatal Databank between 1986 and 2006. Cases were women who developed pre-eclampsia in their second pregnancy and controls were normotensive in their second pregnancy. Crude and adjusted odds ratios were produced for each of the risk factors using logistic regression. Results Inter-pregnancy intervals of 6 years or more were associated with increased incidence of pre-eclampsia (19.4% vs. 14.7%). A change of partner had a protective effect while an increase in BMI increased the risk of pre-eclampsia. A history of pre-eclampsia was associated with 5 times higher risk {adjusted O.R. 5.12 (95% C.I. 4.42–6.48)} of pre-eclampsia in the second pregnancy. Compared to a term delivery, a previous second trimester pregnancy loss was associated with a 4 times higher risk {adjusted O.R. 4.22 (95% C.I. 2.54–7.03)} of pre-eclampsia in the next pregnancy. Previous very preterm and preterm births were associated with adjusted odds ratios of 2.32 (95% C.I. 1.62–3.32) and 1.62 (95% C.I. 1.46–1.72) respectively. The risk of pre-eclampsia was no higher in women with a previous history of fetal death after 20 weeks than those with a previous live birth, after adjusting for pre-eclampsia in the first pregnancy. Conclusion Only initial deliveries beyond 37 weeks, irrespective of outcome, were protective against pre-eclampsia in the second pregnancy.

A routine detailed ultrasound examination performed at 20 weeks’ gestation demonstrated the presence of nuchal thickening as an apparently isolated finding. The concentration of maternal α -fetoprotein was normal and the risk of Down’s syndrome was 1 in 6800. Amniocentesis was performed and chromosome analysis showed the karyotype 46,XY, del(11)(q23) found in Jacobsen syndrome. Fetal autopsy performed following medical termination at 23 weeks confirmed the phenotype and internal abnormalities found in Jacobsen syndrome.

Summary Reasons for performing study: Following a period of airway inflammation the clearance of inflammatory cells along the mucociliary escalator may impose a considerable oxidant load on the trachea. Objectives: To determine the degree of oxidative stress in tracheal epithelial lining fluid (ELF) in comparison to that present in peripheral airways after an acute exposure to organic dust. Methods: Tracheal wash fluid and bronchoalveolar lavage fluid (BALF) were collected for cytology and antioxidant analyses from 6 recurrent airway obstruction (RAO)-affected horses and 6 healthy control horses before and after stabling on straw bedding for 24 h. Results: In RAO-affected horses, organic dust exposure resulted in a significant decrease in ascorbic acid concentration in tracheal ELF (P < 0.0001), which was greater than the decrease in bronchoalveolar ELF (P = 0.0003). The percentage decrease in tracheal ELF ascorbic acid correlated with the percentage decrease in bronchoalveolar ELF ascorbic acid (r = 0.76; P = 0.004) following exposure. Conclusions: Acute organic dust exposure results in significant antioxidant depletion in the trachea, which may reflect inflammation and oxidative processes in peripheral airways. Potential relevance: Further work is required to evaluate the role of ascorbic acid depletion in the pathogenesis of RAO.

Objectives Prenatal diagnosis by karyotype analysis determines the copy number and structure of each chromosome and is considered to be the ‘gold standard’ in detection of chromosome abnormality. This method is, however, time consuming and women may have to wait up to 21 days for the results. With improving molecular genetic techniques, the most commonly occurring chromosome abnormalities can be diagnosed within 2 days from amniotic fluid. This study investigates the value pregnant women place on these alternative prenatal diagnostic tests. Methods A structured self-completion discrete choice experiment questionnaire was designed. The subjects were 40 pregnant women, of unknown risk, attending for their 11-week booking scan and 10 elevated-risk women attending for amniocentesis at the Aberdeen Maternity Hospital, Scotland. Results Women value ‘comprehensive’ information of a full karyotype analysis at £791, and ‘simple’ information of a rapid diagnostic test at £690. Willingness to pay for a day's reduction in waiting time for results is £18. Women prefer a prenatal service providing simple over comprehensive information as long as they receive results 6 days sooner than the comprehensive results would be provided. Conclusions While women prefer comprehensive information, the bulk of the value is placed on knowing whether the fetus has Down syndrome. Given the longer wait times for comprehensive information, simple information is preferred as long as results are received 6 days sooner than would be the case for comprehensive information. These results have implications for the resources dedicated to providing a rapid prenatal diagnostic service. Copyright © 2005 John Wiley & Sons, Ltd.

Effects of acute airway inflammation induced by organic dust inhalation on pulmonary antioxidant status were investigated in healthy horses and horses affected by recurrent airway obstruction. Exposure to organic dust induced acute airway neutrophilia, which was associated with increases in elastase and decreases in ascorbic acid concentrations in bronchoalveolar lavage fluid. However, markers of oxidative stress were unaffected, as was hydrogen peroxide in breath condensate. Decreases in ascorbic acid correlated with increased respiratory resistance (P = .001) when both groups were combined. In conclusion, acute neutrophilic airway inflammation does not result in significant evidence of oxidative stress in horses affected by recurrent airway obstruction.

Close scrutiny of the maternity services in Scotland has been necessary because of the falling birth rate, the European working time directive, the geographically diverse population and the public expectation of good quality care. This article describes how this is being done.

The relationship between hydrogen peroxide (H2O2) concentration in expired breath condensate (EBC) and cytology of the respiratory tract obtained from tracheal wash (TW) or bronchoalveolar lavage (BAL), and epithelial lining fluid (ELF) antioxidant status is unknown. To examine this we analysed the concentration of H2O2 in breath condensate from healthy horses and horses affected by recurrent airway obstruction (RAO), a condition considered to be an animal model of human asthma. The degree of airway inflammation was determined by assessing TW inflammation as mucus, cell density and neutrophil scores, and by BAL cytology. ELF antioxidant status was determined by measurement of ascorbic acid, dehydroascorbate, reduced and oxidised glutathione, uric acid and alpha-tocopherol concentrations. RAO-affected horses with marked airway inflammation had significantly higher concentrations of breath condensate H2O2 than control horses and RAO-affected horses in the absence of inflammation (2.0 +/- 0.5 micromol/l. 0.4 +/- 0.2 micromol/l and 0.9 +/- 0.2 micromol/l H2O2, respectively; p0.0001). The concentration of breath condensate H2O2 was related inversely to the concentration of ascorbic acid in ELF (r = -0.80; p0.0001) and correlated positively with TW inflammation score (r = 0.76, p0.0001) and BAL neutrophil count (r = 0.80, p0.0001). We conclude that the concentration of H2O2 in breath condensate influences the ELF ascorbic acid concentration and provides a non-invasive diagnostic indicator of the severity of neutrophilic airway inflammation.

Objective—To determine the pulmonary epithelial lining fluid (ELF) concentrations and degree of oxidation of ascorbic acid in horses affected by recurrent airway obstruction (RAO) in the presence and absence of neutrophilic airway inflammation. Animals—6 RAO-affected horses and 8 healthy control horses. Procedure—Nonenzymatic antioxidant concentrations were determined in RBC, plasma, and ELF samples of control horses and RAO-affected horses in the presence and absence of airway inflammation. Results—ELF ascorbic acid concentration was decreased in RAO-affected horses with airway inflammation (median, 0.06 mmol/L; 25th and 75th percentiles, 0.0 and 0.4 mmol/L), compared with RAOaffected horses without airway inflammation (1.0 mmol/L; 0.7 and 1.5 mmol/L) and control horses (2.2 mmol/L; 1.4 and 2.2 mmol/L). Epithelial lining fluid ascorbic acid remained significantly lower in RAOaffected horses without airway inflammation than in control horses. Moreover, the ELF ascorbic acid redox ratio (ie, ratio of the concentrations of dehydroascorbate to total ascorbic acid) was higher in RAO-affected horses with airway inflammation (median, 0.85; 25th and 75th percentiles, 0.25 and 1.00), compared with RAOaffected horses without airway inflammation (0.04; 0.02 and 0.22). The number of neutrophils in bronchoalveolar lavage fluid was inversely related to the ELF ascorbic acid concentration ( r = –0.81) and positively correlated with the ascorbic acid redox ratio ( r= 0.65). Conclusions and Clinical Relevance—Neutrophilic inflammation in horses affected by RAO is associated with a reduction in the ELF ascorbic acid pool. Nutritional supplementation with ascorbic acid derivatives in horses affected by RAO is an area for further investigation. ( Am J Vet Res2004;65:80–87)

Fractures of the little finger metacarpal are common, and are often associated with significant soft-tissue swelling and the appearance of rotational malalignment when the fingers are flexed. Our hypothesis is that soft-tissue swelling causes this apparent rotational deformity of the flexed little finger. The fourth intermetacarpal spaces of three of the authors’ non-dominant hands were injected with saline. Following injection, all the hands exhibited the appearance of internal rotation of the little finger. The mean change in rotation was 16° and the maximum was 25°. There was no change in the plane of the nail plate in extension in any hand. We conclude that soft-tissue swelling can cause the appearance of internal rotation of the flexed little finger in the absence of fracture.

Two TaqMan PCR assays have been developed to test for Ralstonia solanacearum. One assay (RS) was genus specific, reacting with all strains of R. solanacearum but also the Banana blood disease bacterium and R. syzygii. Another assay (B2) was specific for Biovar 2 (Race 3) strains which cause brown rot of potatoes. The selective media SMSA and Willbrinks medium have been modified into broth form to detect the pathogen in complex substrates, such as sewage and river water, where population numbers are often low. Using these media in a pre-enrichment real-time bio PCR assay facilitates the robust, highly sensitive detection of the potato brown rot pathogen in natural samples including tubers and waste water.