Developing a novel risk prediction model for severe malarial anemia.

As a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002-2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as a Plasmodium falciparum infection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1ß provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.77 (95% CI 0.70-0.84), whereas a pragmatic model based on sex, gravidity, transmission season at delivery, and bed net possession yielded a more modest C-index of 0.63 (95% CI 0.54-0.71). Although additional studies, ideally incorporating larger sample sizes and higher event per predictor ratios, are needed to externally validate these prediction models, the findings provide proof of concept that risk score-based screening programs could be developed to avert severe malaria cases in early childhood.

Correction: Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein.

[This corrects the article DOI: 10.1371/journal.pone.0159449.].

Femoral Head Growth Plate Dysplasia and Fracture in Juvenile Rabbits Induced by Off-target Antiangiogenic Treatment.

Epiphyseal growth plate dysplasia (chondrodysplasia) might be considered as the pathognomonic feature of antiangiogenic treatment in preclinical species as it is reliably and dose-responsively induced in rodents and monkeys with vascular endothelial growth factor receptor (VEGFR) inhibitors, fibroblast growth factor (FGF) receptor inhibitors, matrix metalloproteinase inhibitors, and vascular targeting agents. Here we report epiphyseal growth plate dysplasia in juvenile rabbits treated with an oral spleen tyrosine kinase inhibitor induced by off-target antiangiogenic inhibition of VEGF and FGF family kinase receptors. Epiphyseal growth plate dysplasia resulted in weakening and fracturing of the femoral head physis in 6 of 10 male and 1 of 10 female animals as well as microfracturing and dysplasia of the distal femoral articular cartilage in 1 male animal. Fracture lines ran through the zone of hypertrophic cartilage (as well as adjacent zones), were orientated parallel to the physeal plane, and often involved displacement of the femoral head. We would suggest that the high prevalence of growth plate fracture in the rabbit may represent a potential additional adverse risk to those already established for children treated with antiangiogenic therapy.

Key Factors Affecting Reproductive Success of Thoroughbred Mares and Stallions on a Commercial Stud Farm.

To evaluate factors contributing to fertility of thoroughbred mares, data from 3743 oestrous periods of 2385 mares were collected on a large thoroughbred farm in Ireland. Fourteen stallions (mean age 8.3 years; range 4-15 years) had bred 2385 mares (mean age 9.4 years; range 3-24 years). Maiden mares accounted for 12%, mares with a foal at foot for 64%, and barren, slipped or rested mares for 24% of the total. The mean pregnancy rate per cycle was 67.8% (68.6% in year 1 and 66.9% in year 2). Backward stepwise multivariable logistic regression analysis was utilized to develop two models to evaluate mare factors, including mare age, reproductive status, month of foaling, dystocia, month of cover, foal heat, cycle number, treatments, walk-in status and stallion factors including stallion identity, stallion age, shuttle status, time elapsed between covers and high stallion usage on the per cycle pregnancy rate and pregnancy loss. Old age (p < 0.001) and cover within 20 days post-partum (p < 0.003) were associated with lowered pregnancy rates. High mare age (p < 0.05) and barren, slipped or rested reproductive status (p = 0.05) increased the likelihood of pregnancy loss. Uterine inflammation or infection, if appropriately treated, did not affect fertility. Only high usage of stallions (used more than 21 times in previous week) was associated with lowered (p = 0.009) pregnancy rates. However, shuttle stallions were more likely to have increased (p = 0.035) pregnancy survival, perhaps reflecting a bias in stallion selection. In conclusion, mare age exerted the greatest influence on fertility; nonetheless, thoroughbreds can be effectively managed to achieve high reproductive performance in a commercial setting.

Effect of combined exogenous progesterone with luteotrophic support via equine chorionic gonadotrophin (eCG) on corpus luteum development, circulating progesterone concentrations and embryo development in cattle.

The aim was to examine the effect of a single intramuscular (i.m.) injection of equine chorionic gonadotrophin (eCG) on Day 3 after oestrus on corpus luteum (CL) development, circulating progesterone and conceptus development in cross-bred beef heifers. In Experiment 1, heifers received: (1) saline, or a single i.m. injection of eCG on Day 3 at (2) 250IU (3) 500IU (4) 750IU or (5) 1000IU. Administration of eCG resulted in increased luteal tissue area and progesterone and oestradiol concentrations compared with controls. In Experiment 2, heifers received (1) a progesterone-releasing intravaginal device (PRID Delta) from Day 3 to 5 or (2) a PRID Delta from Day 3 to 5 plus a single injection of 750IU eCG on Day 3. In vitro-produced blastocysts (n=10 per recipient) were transferred on Day 7 and heifers were slaughtered on Day 14 to assess conceptus development. Administration of eCG reduced the number of short cycles (6.3% vs 31.3%) and increased mean luteal tissue weight (P=0.02). Insertion of a PRID Delta on Day 3 resulted in an elevation (P<0.05) in serum progesterone until removal on Day 5. Administration of eCG at the time of PRID Delta insertion resulted in higher progesterone levels (P<0.05) from Day 10 onwards. Conceptus dimensions were not affected. In conclusion, a single injection of eCG on Day 3 increased CL size and progesterone concentrations and, when given in conjunction with a progesterone-releasing device, appeared to reduce the number of short cycles, presumably due to its luteotrophic nature. The implications of the elevated oestradiol concentrations for embryo quality require further study.

The relationship between activity clusters detected by an automatic activity monitor and endocrine changes during the periestrous period in lactating dairy cows.

The aim of this study was to determine the relationship between observed estrous-related behavior, activity clusters (AC; detected by automatic activity monitor), endocrine profiles, and ovulation time. Twenty-one cows in estrus (after 2 cloprostenol treatments, 11 d apart) and 12 nonsynchronized cows, to establish Heatime (SCR Engineers Ltd., Netanya, Israel) herd baseline activity, were enrolled. Cows had Heatime monitors applied 3 wk before the trial to establish their own baseline activity level. Cows in standing estrus had ultrasonography and phlebotomy carried out every 4 h to determine dominant follicle size, endocrine profiles, and ovulation time. After ovulation, these procedures were repeated once on d 3 to 6. Heatime alerted estrus in 90% of cows, and incorrectly alerted 17% of AC. The mean±SEM duration for standing estrus was 9±1 and 13±1 h for estrous-related behavior. Estrous-related behavior began after the start of the proestrous estradiol-17ß (E2) increase (59±6.5 h). Cows with longer durations of raised proestrous E2 had longer intervals from its onset to the start of standing estrus and AC. The AC duration increased with longer durations of estrous-related behavior. Higher peak E2 occurred with longer standing estrus and estrous-related behavior. As E2 concentration decreased after the peak, 90% of cows still had estrous-related behavior. Duration of estrous-related behavior increased with higher average E2 concentration during the last 8 h before the start of the LH surge. During this surge 90% of cows had all of their standing estrus. As yields increased, so did the magnitude of the preovulatory FSH surges. Higher surges occurred with shorter standing estrus and estrous-related behavior. Cows with shorter LH surges had longer standing estrus. Peak LH preceded the AC peak (6.6±0.8 h). Duration of overlap between the AC start and the LH surge end ranged between 0 and 14 h; 1 cow had none. No association was found between the AC characteristics with the E2, LH, or FSH profiles. In conclusion, the relationship between the timing of the E2 increase and estrous activity may be mediated by other factors (GnRH surge). Estrous-related behavior, but not endocrine profiles, was related to AC duration. Timing of standing estrus during the LH surge ensures that mating allows sperm maturation before ovulation. Based on the interval from the start of an AC to ovulation (27±1 h), the optimum time to artificial insemination is, on average, between 9 and 15 h after the AC start.

Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI.

RATIONALE: Acute administration of the recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has previously been shown to increase cerebro-cortical perfusion as determined by bolus-tracking arterial spin labelling (btASL) MRI. OBJECTIVES: The purpose of the current study was to assess the mechanisms mediating these changes following systemic administration of MDMA to rats. METHODS: Pharmacological manipulation of serotonergic, dopaminergic and nitrergic transmission was carried out to determine the mechanism of action of MDMA-induced increases in cortical perfusion using btASL MRI. RESULTS: Fenfluramine (10 mg/kg), like MDMA (20 mg/kg), increased cortical perfusion. Increased cortical perfusion was not obtained with the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodophenyl-aminopropane hydrochloride (DOI) (1 mg/kg). Depletion of central 5-HT following systemic administration of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (pCPA) produced effects similar to those observed with MDMA. Pre-treatment with the 5-HT receptor antagonist metergoline (4 mg/kg) or with the 5-HT reuptake inhibitor citalopram (30 mg/kg), however, failed to produce any effect alone or influence the response to MDMA. Pre-treatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg) failed to influence the changes in cortical perfusion obtained with MDMA. Treatment with the neuronal nitric oxide (NO) synthase inhibitor 7-nitroindazole (7-NI) (25 mg/kg) provoked no change in cerebral perfusion alone yet attenuated the MDMA-related increase in cortical perfusion. CONCLUSIONS: Cortical 5-HT depletion is associated with increases in perfusion although this mechanism alone does not account for MDMA-related changes. A role for NO, a key regulator of cerebrovascular perfusion, is implicated in MDMA-induced increases in cortical perfusion.

Ultrasound monitoring of blood flow and echotexture of the corpus luteum and uterus during early pregnancy of beef heifers.

The aim was to characterize changes in the ultrasound characteristics of the CL and uterus in pregnant, inseminated nonpregnant, and cyclic beef heifers and to correlate findings with systemic progesterone (P4) concentrations with the intention of identifying possible markers for early identification of pregnancy. Heifers were randomly selected for artificial insemination after estrus synchronization. Ultrasound examinations of the CL and uterus were carried out by transrectal ultrasonography using a high-resolution ultrasound scanner equipped with a 12 MHz linear array probe on Days 7, 11, 14, 16, and 18 after artificial insemination (Day 0; i.e., estrus). Cross-sectional B-mode images of the CL were captured for calculation of CL tissue area and echotexture. Images of the CL and associated blood flow were captured and stored for analysis of luteal blood flow area and ratio. Longitudinal B-mode images of the uterine horns were captured just beyond the bifurcation of the uterine horns and stored for analysis of contrast and homogeneity (MaZda v4.6; Technical University of Lodz, Institute of Electronics, Poland). A total of three images were captured for each structure of interest. Serum concentrations of P4 were determined from blood samples collected at each ultrasound examination. After pregnancy diagnosis by ultrasound, heifers were retrospectively allocated as being pregnant (embryonic heartbeat on Day 28; n = 14) or nonpregnant (interestrous interval 18-21 days; n = 8) and their data were compared with noninseminated cyclic heifers (n = 10). Corpus luteum tissue area did not appear to change between pregnant, nonpregnant, or cyclic control groups between Days 7 and 18 (P > 0.05). No significant differences in CL echotexture characteristics were found between groups at any time point. There were no significant differences between pregnant, nonpregnant, and cyclic control groups for CL blood flow area (P > 0.05). However, CL blood flow ratio decreased significantly (P < 0.05) in both inseminated nonpregnant and cyclic heifers between Days 14 and 18, whereas it remained unchanged in pregnant heifers (P > 0.05). Uterine homogeneity was not significantly different between groups at any time point (P > 0.05). However, uterine contrast was significantly greater (P < 0.05) in pregnant compared with cyclic control heifers on Days 16 and 18. Concentrations of P4 were lower (P < 0.05) in nonpregnant and control heifers than in pregnant heifers from Days 16 to 18. In conclusion, there were differences between nonpregnant and cyclic heifers compared with pregnant heifers in P4 concentrations from Day 16. On Day 18, the CL and uterine characteristics were different between the nonpregnant and pregnant heifers. Ultrasound measures of CL blood flow and uterine echotexture may be useful to establish pregnancy status. Further investigation is required to identify if pregnancy diagnosis can be made on Day 18 or at a later day postpartum.

Hormonal composition of follicular fluid from abnormal follicular structures in mares.

The objective was to characterise the hormonal composition of follicular fluid from mares with distinct anovulatory-cystic follicles. Follicular fluid was aspirated from six mares that presented with cystic follicles and from pre-ovulatory follicles of five normal mares (controls). Differences in progesterone, oestradiol, testosterone, IGF-I and IGF binding were analysed using Fisher's exact test. There were greater (P < 0.03) follicular fluid oestradiol concentrations in normal follicles and the testosterone concentration of the cystic fluid was greater (P < 0.05) than that of the normal fluid. There also was a greater (P < 0.03) percentage of IGF-I binding and lower (P < 0.02) IGF-I concentrations in the fluid collected from the cystic structures compared with the fluid from normal follicles. Despite the limited number of animals, the fact that fluid aspirated from cystic follicles had higher testosterone and lower oestradiol concentrations could be of diagnostic value when a practitioner wants to distinguish between a cystic and non-cystic persistent follicle. The research reported here also indicates a likely role for the IGF system in the pathogenesis of the development and maintenance of anovulatory follicular structures in mare ovaries.

Primary bladder exstrophy closure in neonates: challenging the traditions.

PURPOSE: We describe a novel approach to neonatal bladder exstrophy closure that challenges the role of postoperative immobilization and pelvic osteotomy. MATERIALS AND METHODS: We reviewed the primary management of bladder exstrophy at our institutions between 2007 and 2011. In particular we compared postoperative management in the surgical ward using epidural analgesia to muscle paralysis and ventilation in the intensive care unit. Clinical outcome measures were time to full feed, length of stay, postoperative complications and redo closure. Cost-effectiveness was also evaluated using hospital financial data. Data are expressed as median (range). Significance was explored by Fisher exact test and unpaired t-test. RESULTS: A total of 74 patients underwent primary closure without osteotomy. Successful closure was achieved in 70 patients (95%). A total of 48 cases (65%) were managed on the ward (group A) and 26 (35%) were transferred to the intensive care unit (group B). The 2 groups were homogeneous for gestational age (median 39 weeks, range 27 to 41) and age at closure (3 days, 1 to 152). Complications requiring surgical treatment were noted in 4 patients (8.3%) in group A and 3 (11.5%) in group B (p = 0.609). Length of stay was significantly shorter for the group managed on the ward (11 vs 18 days, p <0.0001). Median costs were $42,732 for patients admitted to the intensive care unit and $16,214 for those admitted directly to the surgical ward (p <0.0001). CONCLUSIONS: Primary closure of bladder exstrophy without lower limb immobilization and osteotomy is feasible. Postoperative care on the surgical ward using epidural analgesia results in shorter hospitalization.

Effect of hCG administration during corpus luteum establishment on subsequent corpus luteum development and circulating progesterone concentrations in beef heifers.

This study examined the effect of a single administration of human chorionic gonadotrophin (hCG) on Day 1 to 4 after oestrus on corpus luteum (CL) development and circulating progesterone (P4). Oestrus-synchronized heifers (n=43) were administered a single intramuscular injection of saline on Day 1 (control) or 3000IU hCG on Day 1, 2, 3 or 4 after oestrus. Administration of hCG on Day 1 had no effect on CL area, on Day 2 increased CL area from Day 6 to 12 (P<0.05), on Day 3 increased CL area from Day 9 to 11, while on Day 4 increased CL size on Days 9 and 10 (P<0.05). Administration of hCG on Day 4 induced the formation of an accessory CL in 89% of heifers, resulting in a significant increase in total luteal tissue area on the ovaries compared with all other groups. Consistent with the effects on the CL, hCG on Day 1 did not affect P4 concentrations, on Day 2 significantly increased P4 compared with the control from Day 6 to 11 (P<0.05), on Day 3 resulted in a non-significant increase in P4 while hCG on Day 4 increased P4 from Day 8 to 13 compared with the control (P<0.05). In conclusion, administration of hCG as early as Day 2 after oestrus results in increased P4 in circulation from Day 6, which should have beneficial downstream effects in terms of uterine receptivity and conceptus elongation.

The contribution of VEGF signalling to fostamatinib-induced blood pressure elevation.

BACKGROUND AND PURPOSE: Fostamatinib is an inhibitor of spleen tyrosine kinase (TK). In patients, fostamatinib treatment was associated with increased BP. Some TK inhibitors cause BP elevation, by inhibiting the VEGF receptor 2 (VEGFR2). Here, we have assessed the mechanistic link between fostamatinib-induced BP elevation and inhibition of VEGF signalling. EXPERIMENTAL APPROACH: We used conscious rats with automated blood sampling and radio telemetry and anaesthetized rats to measure cardiovascular changes. Rat isolated aorta and isolated hearts, and human resistance vessels in vitro were also used. NO production by human microvascular endothelial cells was measured with the NO-dependent probe, DAF-FM and VEGFR2 phosphorylation was determined in mouse lung, ex vivo. KEY RESULTS: In conscious rats, fostamatinib dose-dependently increased BP. The time course of the BP effect correlated closely with the plasma concentrations of R406 (the active metabolite of fostamatinib). In anaesthetized rats, infusion of R406 increased BP and decreased femoral arterial conductance. Endothelial function was unaffected, as infusion of R406 did not inhibit hyperaemia- or ACh-induced vasodilatation in rats. R406 did not affect contraction of isolated blood vessels. R406 inhibited VEGF-stimulated NO production from human endothelial cells in vitro, and treatment with R406 inhibited VEGFR2 phosphorylation in vivo. R406 inhibited VEGF-induced hypotension in anaesthetized rats. CONCLUSIONS AND IMPLICATIONS: Increased vascular resistance, secondary to reduced VEGF-induced NO release from endothelium, may contribute to BP increases observed with fostamatanib. This is consistent with the elevated BP induced by other drugs inhibiting VEGF signalling, although the contribution of other mechanisms cannot be excluded.

Coronal plane partial articular fractures of the distal femoral condyle: current concepts in management.

Coronal plane fractures of the posterior femoral condyle, also known as Hoffa fractures, are rare. Lateral fractures are three times more common than medial fractures, although the reason for this is not clear. The exact mechanism of injury is likely to be a vertical shear force on the posterior femoral condyle with varying degrees of knee flexion. These fractures are commonly associated with high-energy trauma and are a diagnostic and surgical challenge. Hoffa fractures are often associated with inter- or supracondylar distal femoral fractures and CT scans are useful in delineating the coronal shear component, which can easily be missed. There are few recommendations in the literature regarding the surgical approach and methods of fixation that may be used for this injury. Non-operative treatment has been associated with poor outcomes. The goals of treatment are anatomical reduction of the articular surface with rigid, stable fixation to allow early mobilisation in order to restore function. A surgical approach that allows access to the posterior aspect of the femoral condyle is described and the use of postero-anterior lag screws with or without an additional buttress plate for fixation of these difficult fractures.

The effect of lactation on post-partum uterine involution in Holstein dairy cows.

The objective was to examine the effect of lactation on uterine involution in post-partum dairy cows. Holstein primiparous cows were used (n = 19, mean age: 3.9 ± 0.1 years). At calving, cows were randomly assigned to one of two treatment groups, lactating (n = 11) or non-lactating (i.e. dried off at calving, n = 8). Examination of the reproductive tract was carried out by ultrasonography twice weekly until week 7 post-partum. Blood samples were collected twice weekly for the analysis of progesterone to indicate the resumption of cyclicity and metabolites indicative of energy status. Uterine involution was assessed in terms of size of the uterine horns, uterine body diameter and uterine fluid volume as assessed by the amount of non-echogenic material measured by ultrasound and position of the uterus. Vaginal mucous score was taken on day 28 post-partum for the assessment of uterine inflammation. Resumption of cyclicity (serum progesterone > 1 ng/ml) had occurred in both groups on average by day 21 post-partum. Concentrations of non-esterified fatty acids and beta-hydroxybutyrate were higher, whereas concentrations of glucose, insulin and IGF-1 were lower (p < 0.05) in lactating compared to non-lactating cows. Lactating cows had a smaller mean uterine body diameter (p < 0.05) than non-lactating cows from days 28 to 42 post-partum (day 28: 20.2 ± 1.3 vs 24.9 ± 1.5 mm, respectively) and had a lower mean uterine fluid volume up to day 49 (p < 0.05). By day 49, there was no difference in uterine diameter (15.2 ± 1.8 vs 15.2 ± 1.6 mm) or uterine fluid volume (0.11 ± 0.38 vs 0.18 ± 0.46) between lactating and non-lactating cows, respectively. Vaginal mucous score revealed no evidence of uterine inflammation in either group. In conclusion, while lactation induced significant alterations in metabolic status, it did not have a major effect on the rate of uterine involution as defined in this study.

MDMA 'ecstasy' increases cerebral cortical perfusion determined by bolus-tracking arterial spin labelling (btASL) MRI.

BACKGROUND AND PURPOSE: The purpose of this study was to assess cerebral perfusion changes following systemic administration of the recreational drug 3,4-methylendioxymethamphetamine (MDMA 'ecstasy') to rats. EXPERIMENTAL APPROACH: Cerebral perfusion was quantified using bolus-tracking arterial spin labelling (btASL) MRI. Rats received MDMA (20 mg·kg(-1); i.p.) and were assessed 1, 3 or 24 h later. Rats received MDMA (5 or 20 mg·kg(-1); i.p.) and were assessed 3 h later. In addition, rats received MDMA (5 or 10 mg·kg(-1); i.p.) or saline four times daily over 2 consecutive days and were assessed 8 weeks later. Perfusion-weighted images were generated in a 7 tesla (7T) MRI scanner and experimental data was fitted to a quantitative model of cerebral perfusion to generate mean transit time (MTT), capillary transit time (CTT) and signal amplitude. KEY RESULTS: MDMA reduces MTT and CTT and increases amplitude in somatosensory and motor cortex 1 and 3 h following administration, indicative of an increase in perfusion. Prior exposure to MDMA provoked a long-term reduction in cortical 5-HT concentration, but did not produce a sustained effect on cerebral cortical perfusion. The response to acute MDMA challenge (20 mg·kg(-1); i.p.) was attenuated in these animals indicating adaptation in response to prior MDMA exposure. CONCLUSIONS AND IMPLICATIONS: MDMA provokes changes in cortical perfusion, which are quantifiable by btASL MRI, a neuroimaging tool with translational potential. Future studies are directed towards elucidation of the mechanisms involved and correlating changes in cerebrovascular function with potential behavioural deficits associated with drug use.

Clinical and gonadal features and early surgical management of 45,X/46,XY and 45,X/47,XYY chromosomal mosaicism presenting with genital anomalies.

OBJECTIVE: The 45,X/46,XY and 45,X/47,XYY group of patients includes some of those previously diagnosed with 'mixed gonadal dysgenesis'. Our aim was to establish the clinical and gonadal spectrum, and early surgical management, of patients with chromosomal mosaicism presenting with genital anomalies. PATIENTS AND METHODS: We performed a retrospective review of patients with 45,X/46,XY or 45,X/47,XYY mosaicism presenting with genital ambiguity between 1988 and 2009. At least one gonadal biopsy or gonadectomy specimen was available for each patient. Gonadal histology was re-evaluated by a paediatric pathologist. RESULTS: Of 31 patients with 45,X/46,XY (n = 28) or 45,X/47,XYY (n = 3) mosaicism and genital anomalies, 19 (61%) were raised male. Histology of 46 gonads was available from patients who had undergone a gonadectomy or gonadal biopsy, at a median age of 9.5 months. 18 gonads were palpable at presentation, including 5 (28%) histologically unremarkable testes, 2 streak gonads, and 1 dysgenetic gonad with distinct areas of testicular and ovarian stroma but no oocytes. All intra-abdominal gonads were found to be dysgenetic testes (of which 2 were noted to have pre-malignant changes) or streaks, apart from 1 histologically unremarkable testis. 15 (48%) patients had other anomalies, most commonly cardiac and renal; 4 (13%) had a Turner phenotype. CONCLUSION: The anatomy and gonadal histology of 45,X/46,XY and 45,X/47,XYY individuals with genital ambiguity do not conform to a set pattern, and hence management of each patient should be individualized according to detailed anatomical and histological assessment.

Added value of abdominal cross-sectional imaging (CT or MRI) in staging of Wilms' tumours.

AIM: To assess the added information gained from computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen over abdominal ultrasound in children undergoing staging of Wilms' tumours. MATERIALS AND METHOD: Fifty-two consecutive patients with histologically proven Wilms' tumours were identified. Each had an initial staging abdominal ultrasound followed by either a CT or MRI examination of the abdomen. Details including tumour size, site, and characteristics, presence of lymph nodes, local invasion, evidence of nephroblastomatosis, and any other relevant finding were gathered from the report of each ultrasound and CT or MRI. Each CT/MRI was then re-reviewed by a consultant paediatric radiologist and a paediatric radiology fellow. The difference in findings between the ultrasound and cross-sectional imaging were noted. RESULTS: Twelve patients were excluded from the study because the CT/MRI was performed before the ultrasound, or imaging was incomplete. Twenty-six patients were female, 14 male. The ages ranged from 9 months to 10.8 years (mean 3.75 years). Twenty-one patients out of the remaining 40 had additional findings detected on the CT or MRI examination that had not been reported on the ultrasound. The most important additional findings included three patients with nephroblastomatosis and two with contralateral tumours. Other findings included two patients with tumour haemorrhage, four with abdominal lymph node enlargement, three with inferior vena cava (IVC)/renal vein thrombus, four with adjacent organ invasion, one patient where the origin of the abdominal tumour was confirmed as renal, and one patient where possible liver invasion was excluded. CONCLUSION: In over half the patients, CT or MRI added additional information in the local staging of Wilms' tumours. Sole reliance on ultrasound for Wilms' staging risks missing significant abnormalities.

Effects of diet type on establishment of pregnancy and embryo development in beef heifers.

The objectives were to determine the effects of elevated blood urea concentrations on: (i) the response to superovulation, fertilisation rate, and early embryonic development in beef heifers, and (ii) embryo survival from days 7 to 35 of gestation. In Experiment 1, heifers (18-24 months) were allocated at random (n=20 per treatment) to one of the following diets: (i) ad libitum grass silage plus 5 kg commercial beef concentrates per day (controls); (ii) ad libitum grass silage plus 5 kg concentrates and 250 g feed grade urea per day (HE/HU); or (iii) ad libitum wheaten straw plus 250 g feed grade urea and 50 g vitamin/mineral mix per day (LE/HU). Serum urea concentrations were monitored throughout the experiment. Oestrus in heifers was synchronised using an intravaginal releasing device (CIDR(®), InterAg, New Zealand). Oestrus was detected and in vitro produced blastocysts (day 7, morphological grades 1 and 2) were transferred to the heifers 7 days later (19 days after start of treatment diets). The heifers were maintained on the dietary treatments for a further 28 days, when pregnancy status was determined by transrectal ultrasonography. Detected pregnancies were terminated using 15 mg luprostiol and recycled for Experiment 2. In Experiment 2, following a 14-day dietary rest period, the heifers were re-allocated at random to the three dietary treatments above. Heifers were treated with a CIDR for 8 days and 15 mg luprostiol was given 12h before pessary withdrawal. They received 144 mg pFSH (Folltropin(®)-V, Vetrepharm, Canada) given as 8 injections over 4 days commencing on day 6 of CIDR/dietary treatment. Heifers were artificially inseminated 48 h after progesterone pessary withdrawal using commercial semen of proven fertility by a competent inseminator. The heifers were maintained on their diets until slaughter, 3 days post insemination when corpora lutea numbers were determined and embryos were recovered and cell numbers determined visually. Serum urea concentrations were greater in heifers on LE/HU than in those on HE/HU diets, which in turn were greater than controls (7.1 ± 0.5, 4.9 ± 0.3 and 3.2 ± 0.1 mmol/L, respectively; P<0.05). There was no effect of diet type on pregnancy rate at day 35 (42%, 47% and 46%) and on the number of corpora lutea following superovulation (5.2 ± 0.8, 5.8 ± 1.5 and 6.8 ± 1.1) for heifers on control, HE/HU and LE/HU diets, respectively. The total number of embryos recovered per heifer was not different between the three groups (2.7 ± 0.6, 3.4 ± 1.1 and 4.8 ± 0.8 for heifers on control, HE/HU and LE/HU diets, respectively; P>0.05), but the number of embryos with 8 or more cells at recovery was greater in heifers on LE/HU than on control diets (3.4 ± 0.8 compared with 1.0 ± 0.3; P<0.05). However the percentage of embryos recovered with 8 or more cells was not different between groups (70.0 ± 13.3, 86.9 ± 7.2 and 76.5 ± 7.9%, for heifers on control, HE/HU and LE/HU diets respectively). Fertilisation rate, expressed as the proportion of embryos with more than one cell at recovery relative to the total number of embryos recovered, was less in the heifers on the control diet than in the other two dietary treatments (61.3 ± 11.8, 92.0 ± 3.5 and 86.8 ± 5.4% for heifers on control, HE/HU and LE/HU diets, respectively; P<0.05). Deleterious effects of urea on reproduction were not found, suggesting that adverse effects of urea are likely to take place at the early oocyte development stage prior to ovulation or fertilisation following an increase in protein intake.

Effect of exposing rams to a female stimulus before semen collection on ram libido and semen quality.

Rams with strong libido and desirable semen characteristics can provide more insemination doses per ejaculate and produce more progeny, improving population genetic linkage to improve the accuracy of EBV. The objective of this study was to determine if teasing rams, either by sight and smell alone (Exp. 1), or physical contact (Exp. 2), could improve libido and semen quality of rams. In Exp. 1, there were 3 treatments in which rams were exposed to the sight and smell of the ewe for 1 h: control treatment (n = 5) in which rams were exposed to a ewe not in estrus; non-novel treatment (n = 6) in which rams were exposed to a ewe in estrus and the same ewe was used for semen collection; and novel treatment (n = 6) in which rams were exposed to a ewe in estrus and a different ewe in estrus was used for semen collection. In Exp. 2, rams were individually given full access to a ewe, which had a cotton apron fitted to cover her vulva, for 15 min. The 3 treatments in Exp. 2 were: control treatment (n = 5) in which rams were placed in a pen with a ewe not in estrus; a non-novel treatment (n = 5) in which rams were placed in a pen with a ewe in estrus and the same ewe was used for semen collection; novel treatment (n = 6) in which rams were placed in a pen with a ewe in estrus and a different ewe in estrus was used for semen collection. Experiment 1 was repeated for 5 consecutive days and Exp. 2 was repeated for 4 consecutive days. Data on reaction time, number of mounts, semen volume, semen concentration, sperm wave motion, and progressive linear motion (Exp. 1 only) were collected and analyzed as a randomized complete block design, where rams were initially blocked for breed and age. In Exp. 1, there was an effect of day (P < 0.05) and a treatment × day interaction (P < 0.05) on semen volume, whereas there was also an effect of treatment (P < 0.05) and day (P < 0.01) on semen concentration, which was most evident on d 1. In Exp. 2, there was an effect of treatment on reaction time (P < 0.05) and semen volume (P = 0.08), which was most evident on d 1. This study demonstrates an acute effect on d 1 on semen concentration when rams were exposed to the sight and smell of a ewe in estrus. Alternatively, when rams were stimulated with physical contact of a ewe in estrus, an acute increase in semen volume was evident on d 1. These effects were not evident on subsequent days and thus the overall benefits on ram libido and semen quality of exposing rams to ewes in estrus are minimal.