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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.

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.

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.

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.

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)

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.

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.

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)

Prolonged low-medium intensity exercise is associated with increased oxidative stress in humans. We hypothesized that competitive equine endurance racing would induce changes in circulatory antioxidants and produce systemic oxidative stress. Forty horses competing in a 140-km endurance race in warm conditions [shade temperature 15-19 degrees C; 62-88% relative humidity (%RH)] were sampled before (Pre), immediately after exercise (End) and at approximately 16 h into recovery (+16 h). Plasma ascorbic acid concentration was not different between Pre [11.1 (median); 4.6-20.3 micromol/L (range)] and End [9.7; 3.0-38.9 (range) micromol/L] but was significantly decreased at +16 h (5.5; 2.8-15.5 micromol/L; P0.05). Total red cell hemolysate glutathione (TGSH) concentration was significantly reduced by exercise (Pre 1261; 883-1532 micromol/L; End 1065; 757-1334 micromol/L; P0.05) and at +16 h recovery (1032; 752-1362 micromol/L; P0.05). Glutathione redox ratio was unchanged by exercise but was significantly decreased at +16 h compared with that at both Pre and End (P0.05). The concentration of total barbituric acid reactive substances (TBARS) in plasma was increased compared with that at Pre (309; 66-1048 nmol/L), both at End (408; 170-1196 nmol/L; P0.05) and +16 h (380; 99-1161 nmol/L; P0.05). alpha-Tocopherol was unchanged by exercise or recovery. Mean race speed was 16.5 +/- 1.6 km/h and ranged from 13.9 to 19.7 km/h. Mean speed during competition in horses that completed the full 140 km (n = 28) was significantly correlated with end of exercise ascorbic acid (r = 0.622; P = 0.0004). Although there were increases in creatine phosphokinase (CK), aspartate aminotransferase (AST) and TBARS and a loss of TGSH, this study failed to demonstrate evidence of classical oxidative stress.

Fundamental research into the growth of twins is lacking. Twin growth in utero is commonly assumed to follow similar patterns of growth as that of singletons. This preliminary descriptive study on twin pregnancy aimed to define growth velocity as gestation advances, and to study if twin order, fetal sex, zygosity and chorionicity have any relationship to growth velocity.One hundred and sixty-two women with twin pregnancies had an ultrasound examination at fortnightly intervals from 16 weeks until delivery. Fetal measurements of biparietal diameter, abdominal circumference and femur length were performed at each examination. Growth velocity for each parameter was defined as the difference in measurements for that parameter divided by the time interval between measurements. Postnatally, zygosity and chorionicity were determined by genetic fingerprinting and inspection of the placenta, respectively.Growth velocity for all parameters decreased as gestation advanced, with the downward trend more noticeable after 32 weeks. Maximum and minimum growth occurred at 22-23 weeks and 36-37 weeks, respectively. Maximum and minimum growth velocities for the abdominal circumference were 1.7 and 0.8 cm/week, respectively. Birth order, fetal sex, chorionicity and zygosity were not related to growth velocity.These preliminary results suggest that growth velocity in twins decreases after 32 weeks' gestation. It appears that growth velocity is independent of birth order, fetal sex, chorionicity and zygosity.

Summary The effect of a COPD crisis on arterial blood gases, heart rate, lactate and indices of oxidative stress were investigated before, during and 1 h after a ‘run up to fatigue’ in 6 COPD horses. They were investigated twice, randomly: once in acute crisis (C) and once in clinical remission (R). Arterial and mixed venous blood samples were collected and analysed for partial pressures in O2 and CO2. The mixed venous blood was also analysed for plasma lactate (LA) and packed cell volume (PCV), as well as for indices of oxidative stress, i.e. reduced glutathione, glutathione disulphide, glutathione redox ratio (GRR) and lipid hydroperoxides (LPH). The exercise test was an effort of increasing intensity on a treadmill at 0% slope, which was stopped when the horses showed signs of exhaustion. Their performance was evaluated by the number of steps and the running time in the last step. Heart rate was monitored continuously during the test Blood sampling was performed before, just after and 1 h after the end of the test. The COPD crisis significantly reduced the time to fatigue. However, despite the fact that the exercise intensity and length were lower, peak HR and peak LA were similar in C and R, while arterial hypoxaemia and hypercapnia, and PCV were significantly higher in C, indicating a higher physiological stress in this condition. By contrast, the oxidative stress seemed to be higher in R than in C as suggested by the fact that, 1 h after exercise, GRR and LPH were significantly increased with regards to their pre-exercise values in R and not in C. The fact that exercise did not induce an oxidative stress in C could be partly related to (1) the lower exercise intensity reached by the horses, and (2) to the more severe hypoxaemia experienced in this condition. In conclusion, COPD horses in acute crisis show a significant decrease in performance. The reasons for this exercise intolerance remain unclear, but do not appear to be related to any increase of the oxidative stress in C.

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 alpha-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.

Mills, Paul C., David J. Marlin, Caroline M. Scott, and Nicola C. Smith. Nitric oxide and thermoregulation during exercise in the horse. J. Appl. Physiol. 82(4): 1035–1039, 1997.—The effect of inhibition of nitric oxide production on sweating rate (SR) and on core, rectal, and tail skin temperatures was measured in five Thoroughbred horses during exercise of variable intensity on a high-speed treadmill. A standard exercise test consisting of three canters [∼55% maximum O2uptake (V˙o2 max)], with walking (∼9%V˙o2 max) and trotting (∼22% V˙o2 max) between each canter, was performed twice (control or test), in random order, by each horse. NG-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg), a competitive inhibitor of nitric oxide synthase, was infused into the central circulation and induced a significant reduction in the SR measured on the neck (31.6 ± 6.4 vs. 9.7 ± 4.2 g ⋅ min−1⋅ m−2; 69%) and rump (14.7 ± 5.2 vs. 4.8 ± 1.6 g ⋅ min−1⋅ m−2; 67%) of the horses during canter ( P< 0.05). Significant increases in core, rectal, and tail skin temperatures were also measured ( P < 0.05).l-Arginine (200 mg/kg iv) partially reversed the inhibitory effects ofl-NAME on SR, but core, rectal, and tail skin temperatures continued to increase ( P < 0.05), suggesting a cumulation of body heat. The results support the contention that nitric oxide synthase inhibition diminishes SR, resulting in elevated core and peripheral temperatures leading to deranged thermoregulation during exercise. The inhibition of sweating byl-NAME may be related to peripheral vasoconstriction but may also involve the neurogenic control of sweating.

Objective To determine the optimum interpregnancy interval after miscarriage in a first recorded pregnancy. Design Population based retrospective cohort study. Setting Scottish hospitals between 1981 and 2000. Participants 30 937 women who had a miscarriage in their first recorded pregnancy and subsequently became pregnant. Main outcome measures The primary end point was miscarriage, live birth, termination, stillbirth, or ectopic pregnancy in the second pregnancy. Secondary outcomes were rates of caesarean section and preterm delivery, low birthweight infants, pre-eclampsia, placenta praevia, placental abruption, and induced labour in the second pregnancy. Results Compared with women with an interpregnancy interval of 6-12 months, those who conceived again within six months were less likely to have another miscarriage (adjusted odds ratio 0.66, 95% confidence interval 0.57 to 0.77), termination (0.43, 0.33 to 0.57), or ectopic pregnancy (0.48, 0.34 to 0.69). Women with an interpregnancy interval of more than 24 months were more likely to have an ectopic second pregnancy (1.97, 1.42 to 2.72) or termination (2.40, 1.91 to 3.01). Compared with women with an interpregnancy interval of 6-12 months, women who conceived again within six months and went on to have a live birth in the second pregnancy were less likely to have a caesarean section (0.90, 0.83 to 0.98), preterm delivery (0.89, 0.81 to 0.98), or infant of low birth weight (0.84, 0.71 to 0.89) but were more likely to have an induced labour (1.08, 1.02 to 1.23). Conclusions Women who conceive within six months of an initial miscarriage have the best reproductive outcomes and lowest complication rates in a subsequent pregnancy.

In a consecutive series of 800 routine double contrast studies of the colon, 119 polyps were diagnosed radiologically in 78 patients. Follow-up studies were available in 46 patients with 72 polyps. Ultimately, 56 of these polyps were confirmed (55 by endoscopy and 1 by repeat radiology). Six of these polyps had been missed on the initial endoscopic examination. The missed polyps are usually located in the rectum behind a valve of Houston or in any area of the colon where there is sharp angulation. Radiologists and endoscopists should be aware of these as potential endoscopic blind spots. These cases illustrate the importance of higg quality radiological study of the colon and the complementary nature of radiology and endoscopy in the detection of colorectal polyps.

A series of 19 non-virginal patients who sustained vaginal injuries during normal coitus is presented. Twelve were between 16 and 25 years of age and 5 were older than 45 years. All presented with profuse or prolonged vaginal bleeding. The initial diagnosis was frequently wrong because a history of injury was not forthcoming and visualization of the lesion was obscured by the bleeding. The possibility of such trauma should be kept in mind; digital examination confirms the diagnosis. Prompt surgical suturing under general anaesthesia is required to control the haemorrhage.