Traumatic suprahepatic inferior vena cava injury: surgical management

SUMMARY:: Suprahepatic inferior vena caval (IVC) injuries are rare but carry nearly a 100% mortality rate. The main problem with its surgical management is the technical difficulty in draining the IVC during cardiopulmonary bypass. In this report, an efficient method of IVC drainage for repair of the IVC on cardiopulmonary bypass is described.     

Effects of an individually ventilated cage system on the airway integrity of rats (Rattus norvegicus) in a laboratory in Brazil

The ventilation method used in the management of laboratory rats is important in maintaining their health. Rats kept under general diluting ventilation (GDV) are exposed to high levels of pollutants present in the environment (dust, airborne bacteria, etc.) or those pollutants produced by animal metabolism and excretion inside the boxes (e.g. ammonia and carbon dioxide). These pollutants may contribute to respiratory pathologies. An alternative experimental ventilation system for laboratory animal housing using intracage ventilation technology (individually ventilated cage system, IVC) was developed. In this system, ammonia levels decreased and rats exhibited better reproductive performance and a lower incidence of pneumonia than rats maintained under GDV. Using two different levels of air speed (0.03-0.26 m/s: IVC(1); 0.27-0.80 m/s: IVC(2)), the effects of IVC were compared with GDV (control) in Wistar rats in terms of respiratory mucus properties, on the nasal epithelium (as measured by quantitative morphometry) and on the lungs (as determined by the cellular composition obtained by bronchoalveolar lavage). Mucus of the respiratory system was evaluated using the following techniques: rheology (viscoelasticity) by microrheometer, in vitro mucociliary transportability (frog palate) and contact angle (an indicator of adhesivity). Also, membrane transepithelial potential difference was measured as a biomarker of airway integrity. After bedding was changed, ammonia concentrations inside the cages on day 3 were significantly higher for GDV than for IVC(1) and IVC(2). The potential-difference values for IVC(1), IVC(2) and GDV in the epiglottis and in the trachea also showed differences. Although some significant differences were observed across the three groups in counts of some cell types, the intragroup results were highly variable among individuals and inconsistent between sexes. No significant differences in the other parameters were found across groups. These results establish that rats maintained under GDV in relatively unregulated conditions are exposed to factors that can lead to deleterious effects on the ciliated epithelium of the airways, and that these effects can be prevented by the use of IVC.     

Leiomyosarcoma of the inferior vena cava level II involvement: curative resection and reconstruction of renal veins

ABSTRACT: Leiomyosarcoma of the inferior vena cava (IVCL) is a rare retroperitoneal tumor. We report two cases of level II (middle level, renal veins to hepatic veins) IVC Leiomyosarcoma, who underwent en bloc resection with reconstruction of bilateral or left renal venous return using prosthetic grafts. In our cases, IVC is documented to be occluded preoperatively, therefore, radical resection of tumor and/or right kidney was performed and the distal end of inferior vena cava was resected and without caval reconstruction. None of the patients developed edema or acute renal failure post-operatively. After surgical resection, adjuvant radiation therapy was administrated. The patients have been free of recurrence 2 years and 3 months, 9 months after surgery, respectively, indicating the complete surgical resection and radiatiotherapy contribute to the better survival. The reconstruction of inferior vena cava was not considered mandatory in level II IVC leiomyosarcoma, if the retroperitoneal venous collateral pathways have been established. In addition to the curative resection of IVC leiomyosarcoma, the renal vascular reconstruction minimized the risks of procedure-related acute renal failure, and was more physiologically preferable. This concept was reflected in the treatment of the two patients reported on.     

Computational predictions of the embolus-trapping performance of an IVC filter in patient-specific and idealized IVC geometries

Embolus transport simulations are performed to investigate the dependence of inferior vena cava (IVC) filter embolus-trapping performance on IVC anatomy. Simulations are performed using a resolved two-way coupled computational fluid dynamics/six-degree-of-freedom approach. Three IVC geometries are studied: a straight-tube IVC, a patient-averaged IVC, and a patient-specific IVC reconstructed from medical imaging data. Additionally, two sizes of spherical emboli (3 and 5 mm in diameter) and two IVC orientations (supine and upright) are considered. The embolus-trapping efficiency of the IVC filter is quantified for each combination of IVC geometry, embolus size, and IVC orientation by performing 2560 individual simulations. The predicted embolus-trapping efficiencies of the IVC filter range from 10 to 100%, and IVC anatomy is found to have a significant influence on the efficiency results (\(P < 0.0001\)). In the upright IVC orientation, greater secondary flow in the patient-specific IVC geometry decreases the filter embolus-trapping efficiency by 22–30 percentage points compared with the efficiencies predicted in the idealized straight-tube or patient-averaged IVCs. In a supine orientation, the embolus-trapping efficiency of the filter in the idealized IVCs decreases by 21–90 percentage points compared with the upright orientation. In contrast, the embolus-trapping efficiency is insensitive to IVC orientation in the patient-specific IVC. In summary, simulations predict that anatomical features of the IVC that are often neglected in the idealized models used for benchtop testing, such as iliac vein compression and anteroposterior curvature, generate secondary flow and mixing in the IVC and influence the embolus-trapping efficiency of IVC filters. Accordingly, inter-subject variability studies and additional embolus transport investigations that consider patient-specific IVC anatomy are recommended for future work.     

Primary leiomyosarcoma of the inferior vena cava: report of a case diagnosed by fine needle aspiration cytology and confirmed by histopathologic examination

BACKGROUND: Leiomyosarcoma is a malignant neoplasm and can originate within major abdominal veins, including the inferior venacava (IVC). CASE: A 45-year-old woman presented with upper abdominal pain and a mass lesion in the liver and within the lumen of the IVC. A diagnosis of primary leiomyosarcoma of the IVC was made by using imaging techniques,fine needle aspiration cytology and histopathologic examination of the resected specimen. CONCLUSION: In patients presenting with vague upper abdominal pain and radiologic features of a hepatic mass extending to major veins, the rare possibility of primary leiomyosarcoma of the IVC shoald he considered and investigated by both fine needle aspiration cytology and intraoperative histology. Early surgical intervention and/or postoperative chemotherapy and radiotherapy are associated with improved survival.     

NHS Diabetes guideline for the perioperative management of the adult patient with diabetes

These Joint British Diabetes Societies guidelines, commissioned by NHS Diabetes, for the perioperative management of the adult patient undergoing surgery are available in full in the Supporting Information. This document goes through the seven stages of the patient journey when having surgery. These are: primary care referral; surgical outpatients; preoperative assessment; hospital admission; surgery; post-operative care; discharge. Each stage is given its own considerations, outlining the roles and responsibilities of each group of healthcare professionals. The evidence base for the recommendations made at each stage, discussion of controversial areas and references are provided in the report. This document has two key recommendations. Firstly, that the management of the elective adult surgery patients should be with modification to their usual diabetes treatment if the fasting is minimized because the routine use of a variable rate intravenous insulin infusion is not recommended. Secondly, that poor preoperative glycaemic control leads to post-outcomes and thus, where appropriate, needs to be addressed prior to referral for surgery.     

Do individually ventilated cage systems generate a problem for genetic mouse model research?

Technological developments over recent decades have produced a novel housing system for laboratory mice, so‐called ‘individually ventilated cage’ (IVC) systems. IVCs present a cage environment which is different to conventional filter‐top cages (FILTER). Nothing is known about the consequences of IVC housing on genetic mouse models, despite studies reporting IVC‐mediated changes to the phenotypes of inbred mouse strains. Thus, in this study, we systematically compared the established behavioural phenotype of a validated mouse model for the schizophrenia risk gene neuregulin 1 (TM Nrg1 HET) kept in FILTER housing with Nrg1 mutant mice raised in IVC systems. We found that particular schizophrenia‐relevant endophenotypes of TM Nrg1 HETs which had been established and widely published using FILTER housing were altered when mice were raised in IVC housing. IVCs diminished the schizophrenia‐relevant prepulse inhibition deficit of Nrg1 mutant males. Furthermore, IVC housing had a sex‐dependent moderate effect on the locomotive phenotype of Nrg1 mice across test paradigms. Behavioural effects of IVC housing were less prominent in female mice. Thus, transferring the breeding colony of mouse mutants from FILTER to IVC systems can shift disease‐relevant behaviours and therefore challenge the face validity of these mice. Researchers facing an upgrade of their mouse breeding or holding facilities to IVC systems must be aware of the potential impact this upgrade might have on their genetic mouse models. Future publications should provide more details on the cage system used to allow appropriate data comparison across research sites.     

Effects of inspiratory diaphragmatic descent on inferior vena caval venous return.

To explain the contradictory results in the literature regarding the effects of inspiratory diaphragmatic descent on inferior vena caval (IVC) venous return, we evaluated changes in total IVC flow as well as regional splanchnic and nonsplanchnic IVC flows by use of ultrasound flow probes placed around the thoracic and subhepatic abdominal IVC during phrenic nerve stimulation (PNS) in anesthetized open-chest dogs. With the abdomen closed (n = 6), PNS under hypervolemic conditions increased the total IVC flow by enhancing the splanchnic IVC flow, with a transient decrease in the nonsplanchnic IVC flow (P less than 0.05). Under hypovolemic conditions, PNS initially increased the total IVC flow but later decreased the total IVC flow by reducing the nonsplanchnic IVC flow, associated with a venous pressure gradient in the IVC across the diaphragm (P less than 0.05), consistent with development of a vascular waterfall. With the abdomen widely open, the mobile abdominal contents eviscerated, and the subhepatic IVC occluded (n = 5), PNS increased the splanchnic IVC flow associated only with an increase in focal contact pressure over the liver without any increase in general abdominal pressure (Pab) (P less than 0.05). These results suggest that our previously proposed concept of abdominal vascular zone conditions (J. Appl. Physiol. 69: 1961-1972, 1990) is useful as a global approximation to understand the effects of respiratory-induced changes in Pab's on the total and regional IVC venous return. Nonhomogeneous distribution of Pab's during diaphragmatic descent may need to be considered to explain all aspects of the behavior of the intact IVC system.     

Utility of Epinephrine Levels in Determining Adrenal Vein Cannulation During Adrenal Venous Sampling for Primary Aldosteronism

ObjectiveIn patients with primary aldosteronism, adrenal venous sampling (AVS) is performed to determine the presence of unilateral or bilateral adrenal disease. During AVS, verification of catheter positioning within the left adrenal vein (AV) and the right AV by comparison of AV and inferior vena cava (IVC) cortisol levels can be variable. The objective of this study was to determine the utility of AV epinephrine levels in assessing successful AV cannulation.MethodsThis was a single institution, retrospective review of patients who underwent AVS with cosyntropin stimulation for primary aldosteronism between 2009 and 2018. Successful cannulation of the AV was defined by an AV/IVC cortisol ratio selectivity index (SI) ≥3:1. Epinephrine thresholds to predict catheter placement in the AV were determined using logistic regression. The calculated epinephrine thresholds were compared with previously published thresholds.ResultsAVS was performed on 101 consecutive patients and, based on the SI, successful cannulation of the left AV and right AV occurred in 98 (97%) and 91(90%) patients, respectively. The calculated optimal epinephrine threshold to predict AV cannulation was 364 pg/mL (sensitivity, 92.1%; specificity, 94.6%) and the calculated optimal AV/IVC epinephrine ratio threshold was 27.4, (sensitivity, 92.1%; specificity, 91.3%). Among the 14 patients with failed AV cannulation, 3 patients would have been considered to have successful AVS using AV epinephrine levels >364 pg/mL and AV/IVC epinephrine ratio >27.4 thresholds.ConclusionObtaining 2 right AV samples routinely as well as AV and IVC epinephrine levels during AVS could prevent unnecessary repeat AVS in patients with failed AV cannulation based on cortisol-based SI <3:1.     

Impact of IVC housing on emotionality and fear learning in male C3HeB/FeJ and C57BL/6J mice

Housing conditions are known to influence laboratory animal behavior. However, it is not known whether housing mice in individually ventilated cages (IVCs) to maintain optimal hygienic conditions alters behavioral baselines established in conventional housing. This issue is important with regard to comparability and reproducibility of data. Therefore, we investigated the impact of IVC housing on emotionality and fear learning in male C3HeB/FeJ (C3H) and C57BL/6J (B6J) mice housed singly either in conventional type II cages with wire bar lids (Conventional), or in IVCs of the same size, but with smooth, untextured lids (IVC classic), thus acoustically attenuated from external stimuli and with limited climbing facilities compared to Conventional. To evaluate the role of climbing, additional mice were kept in IVCs with lids having wire bars ("grid") added to the inner surface (IVC grid). Spontaneous behavior, sensorimotor behavior, and fear learning were measured. IVC housing reduced activity and enhanced anxiety-related behavior in both strains, whereas grooming latency was reduced in B6J only. IVC housing increased Acoustic Startle Response in C3H but not in B6J mice. The "grid" did not compensate for these IVC housing effects. In contrast, B6J mice in IVC grid performed best in fear potentiated startle while B6J mice in IVC classic performed the worst, suggesting that climbing facilities combined with IVC housing facilitate FPS performance in singly-housed B6J males. Our data show that IVC housing can affect behavioral performance and can modulate behavioral parameters in a general and a strain-specific manner, thus having an impact on mouse functional genomics.     

Transport in rat vessel walls. I. Hydraulic conductivities of the aorta, pulmonary artery, and inferior vena cava with intact and denuded endothelia

In this study, filtration flows through the walls of the rat aorta, pulmonary artery (PA), and inferior vena cava (IVC), vessels with very different susceptibilities to atherosclerosis, were measured as a function of transmural pressure (DeltaP), with intact and denuded endothelium on the same vessel. Aortic hydraulic conductivity (L(p)) is high at 60 mmHg, drops approximately 40% by 100 mmHg, and is pressure independent to 140 mmHg. The trends are similar in the PA and IVC, dropping 42% from 10 to 40 mmHg and flat to 100 mmHg (PA) and dropping 33% from 10 to 20 mmHg and essentially flat to 60 mmHg (IVC). Removal of the endothelium renders L(p)(DeltaP) flat: it increases L(p) of the aorta by approximately 75%, doubles L(p) of the PA, and quadruples L(p) of the IVC. Specific resistance (1/L(p)) of the aortic endothelium is approximately 47% of total resistance; i.e., the endothelium accounts for approximately 47% of the DeltaP drop at 100 mmHg. The PA value is 55% at >40 mmHg, and the IVC value is 23% at 10 mmHg. L(p) of the intact aorta, PA, and IVC are order 10(-8), 10(-7), and 5 x 10(-7) cm.s(-1).mmHg(-1), and wall thicknesses are 145.8 microm (SD 9.3), 78.9 microm (SD 3.3), and 66.1 microm (SD 4.1), respectively. These data are consistent with the different wall structures of the three vessels. The rat aortic L(p) data are quantitatively consistent with rabbit L(p)(DeltaP) (Tedgui A and Lever MJ. Am J Physiol Heart Circ Physiol 247: H784-H791, 1984; Baldwin AL and Wilson LM. Am J Physiol Heart Circ Physiol 264: H26-H32, 1993), suggesting that intimal compression under pressure loading may also play a role in L(p)(DeltaP) in these other vessels. Despite very different driving DeltaP, nominal transmural water fluxes of these three vessels are very similar and, therefore, cannot alone account for their differences in disease susceptibility. The different fates of macromolecular tracers convected by these water fluxes into the walls of these vessels may account for this difference.     

Left sided inferior vena cava duplication and venous thromboembolism: case report and review of literature

The etiology of venous thromboembolism in young patients is frequently associated with hereditary coagulation abnormalities, immunologic diseases, and neoplasia. The advent of radiological advances, namely Computed Tomography (CT) scans and venography has identified vena cava malformations as a new etiologic factor worthy of consideration. In this case report, we describe the unusual occurrence of venous thromboembolism in association with a duplicated inferior vena cava. Duplications of the inferior vena cava (IVC) are seen with an incidence of 0.2% to 3.0% in the general population. Embryogenesis of the IVC is a complex process involving the intricate formation and regression of numerous anastomoses, potentially leading to various anomalies. We present a 23-year-old Caucasian woman with IVC duplication who developed a deep venous thrombosis and multiple pulmonary emboli. Anomaly of the IVC is a rare example of a congenital condition that predisposes to thromboembolism, presumably by favoring venous stasis. This diagnosis should be considered in patients under the age of 30 with spontaneous occurrence of blood clots.     

Live piglets derived from in vitro-produced zygotes vitrified at the pronuclear stage

We report the successful cryopreservation of in vitro-produced porcine zygotes. Follicular oocytes from prepubertal gilts were matured (IVM), fertilized (IVF), and cultured (IVC) in vitro. At 10 or 23 h after IVF, the oocytes were centrifuged to visualize pronuclei. Zygotes with two or three pronuclei were used for solid surface vitrification (SSV). Survival of vitrified-warmed zygotes was determined by their morphology. To assess their developmental competence, vitrified (SSV), cryoprotectant-treated (CPA), and untreated (control) zygotes were subjected to IVC for 6 days. Survival and developmental competence did not differ between control and CPA zygotes. The proportion of live zygotes after SSV and warming (93.4%) was similar to that in the controls (100%). Cleavage and blastocyst formation rates of SSV zygotes after vitrification (71.7% and 15.8%, respectively) were significantly lower than those of controls (86.3% and 24.5%, respectively; ANOVA P<0.05). Blastocyst cell numbers of SSV and control embryos were similar (41.2+/-3.4 and 41.6+/-3.3, respectively). There was no difference in developmental ability between zygotes cryopreserved at an early (10 h after IVF) or late (23 h after IVF) pronuclear stage. Storage in liquid nitrogen had no effect on the in vitro developmental competence of vitrified zygotes beyond the reduction induced by the vitrification itself. When the embryo culture medium was supplemented with 1 muM glutathione, the rate of development of cryopreserved zygotes to the blastocyst stage did not differ significantly from that of control glutathione-treated zygotes (18.6% and 22.1%, respectively). To test their ability to develop to term, vitrified zygotes were transferred to five recipients, resulting in three pregnancies and the production of a total of 17 piglets. These data demonstrate that IVM-IVF porcine zygotes can be cryopreserved at the pronuclear stage effectively without micromanipulation-derived delipation, preserving their full developmental competence to term.     

VX2肿瘤侵犯兔下腔静脉的生物学行为观察

目的建立VX2肿瘤侵犯新西兰兔下腔静脉(IVC)的动物模型,并观察相应的生物学行为。方法经腹直视下,将VX2肿瘤组织块分别种植在28只兔肾以下IVC附近的软组织内,然后随机分为A、B两组。A组术后每周在超声下观察肿瘤的大小、IVC和腹主动脉(AA)管径大小;DSA观察侧支循环建立。B组每周随机解剖4只,取IVC和AA做病理和免疫组化(PCNA)检查,并观察转移情况。结果 1.超声显示:所有肿瘤均种植成功,肿瘤面积大小与生长时间呈明显正相关(r=0.879),IVC管径与肿瘤面积大小显著负相关(r=-0.8295);4周时25%的IVC管腔闭塞,5周时达到91.7%。2.病理和免疫组化显示:3周时IVC管壁中见大量肿瘤细胞;5周时AA管壁中未见肿瘤细胞。3.DSA显示:IVC慢性受侵犯过程中侧枝循环建立良好。4.解剖观察:模型动物在第4周开始出现肝、肺和腹腔转移。结论 VX2肿瘤成瘤率高,其生长变化、对IVC的侵犯和远处器官转移均随生长时间而变化明显。     

Effects of exercise training on airway closure in asthmatics

We previously reported that responsiveness to methacholine (Mch) in the absence of deep inspiration (DI) decreased in healthy subjects after a short course of exercise training. We assessed whether a similar beneficial effect of exercise on airway responsiveness could occur in asthmatics. Nine patients (male/female: 3/6; mean age ± SD: 24 ± 2 yr) with mild untreated asthma [forced expiratory volume in 1 s (FEV(1)): 100 ± 7.4% pred; FEV(1)/vital capacity (VC): 90 ± 6.5%] underwent a series of single-dose Mch bronchoprovocations in the absence of DI in the course of a 10-wk training rowing program (6 h/wk of submaximal and maximal exercise), at baseline (week 0), and at week 5 and 10. The single-dose Mch was established as the dose able to induce ≥15% reduction in inspiratory vital capacity (IVC) and was administered to each subject at every challenge occasion. Five asthmatics (male/female: 1/4; mean age ± SD: 26 ± 3 yr) with similar baseline lung function (FEV(1): 102 ± 7.0% predicted; FEV(1)/VC: 83 ± 6.0%; P = 0.57 and P = 0.06, respectively) not participating in the exercise training program served as controls. In the trained group, the Mch-induced reduction in IVC from baseline was 22 ± 10% at week 0, 13 ± 11% at week 5 (P = 0.03), and 11 ± 8% at week 10 (P = 0.028). The Mch-induced reduction in FEV(1) did not change with exercise (P = 0.69). The reduction in responsiveness induced by exercise was of the same magnitude of that previously obtained in healthy subjects (50% with respect to pretraining). Conversely, Mch-induced reduction in IVC in controls remained unchanged after 10 wk (%reduction IVC at baseline: 21 ± 20%; after 10 wk: 29 ± 14%; P = 0.28). This study indicates that a short course of physical training is capable of reducing airway responsiveness in mild asthmatics.     

Development of an in vitro compartmentalization screen for high-throughput directed evolution of [FeFe] hydrogenases

Background

[FeFe] hydrogenase enzymes catalyze the formation and dissociation of molecular hydrogen with the help of a complex prosthetic group composed of common elements. The development of energy conversion technologies based on these renewable catalysts has been hindered by their extreme oxygen sensitivity. Attempts to improve the enzymes by directed evolution have failed for want of a screening platform capable of throughputs high enough to adequately sample heavily mutated DNA libraries. In vitro compartmentalization (IVC) is a powerful method capable of screening for multiple-turnover enzymatic activity at very high throughputs. Recent advances have allowed [FeFe] hydrogenases to be expressed and activated in the cell-free protein synthesis reactions on which IVC is based; however, IVC is a demanding technique with which many enzymes have proven incompatible.

Methodology/Principal Findings

Here we describe an extremely high-throughput IVC screen for oxygen-tolerant [FeFe] hydrogenases. We demonstrate that the [FeFe] hydrogenase CpI can be expressed and activated within emulsion droplets, and identify a fluorogenic substrate that links activity after oxygen exposure to the generation of a fluorescent signal. We present a screening protocol in which attachment of mutant genes and the proteins they encode to the surfaces of microbeads is followed by three separate emulsion steps for amplification, expression, and evaluation of hydrogenase mutants. We show that beads displaying active hydrogenase can be isolated by fluorescence-activated cell-sorting, and we use the method to enrich such beads from a mock library.

Conclusions/Significance

[FeFe] hydrogenases are the most complex enzymes to be produced by cell-free protein synthesis, and the most challenging targets to which IVC has yet been applied. The technique described here is an enabling step towards the development of biocatalysts for a biological hydrogen economy.     

Radiofrequency Catheter Ablation Of Atrioventricular Nodal Reentry Tachycardia In A Patient With Inferior Vena Cava Anomaly

Curative radiofrequency catheter modification of the slow pathway is the recommended therapy for patients suffering from recurrent symptomatic atrioventricular nodal reentry tachycardia. This is usually performed via femoral vein and the inferior vena cava (IVC). Presence of venous occlusion or complex venous anomaly involving the IVC may preclude this approach. Here, we report a case with a complex venous anomaly involving the inferior vena cava, who underwent electrophysiological study and successful radiofrequency ablation by an alternative approach.     

Principles and practice in ethical review of animal experiments across Europe: summary of the report of a FELASA working group on ethical evaluation of animal experiments

This paper summarizes a more detailed report produced by the Federation of European Laboratory Animal Science Associations (FELASA 2005), which describes and explores a set of principles for the conduct of ethical review of laboratory animal use. It presents a synopsis of results from a questionnaire that elicited information on how each of 20 countries represented in FELASA currently approaches such ethical review. This information suggests that, although local practices differ, there is an emerging consensus on the key elements that any ethical review process should involve. Drawing on the questionnaire findings, this summary also includes a brief discussion to support and amplify a series of recommendations, covering the objectives of ethical review; legal requirements; the scope of work reviewed and the 'level' at which review is approached; general principles for the organization of ethical review processes; the factors considered in the review; needs for ongoing review after initial authorization; participants in the review process; wider impacts of the review process; and strategies that can help to ensure quality and consistency of review outcomes. For further information and examples of current practice, as well as more detailed discussion to support the recommendations, readers are urged to refer to the complete report, available at http://www.lal.org.uk/pdffiles/FELASA_ethics_FULL_Report. pdf or via: http://www.felasa.eu/recommendations.htm.     

Canadian asthma consensus report, 1999

OBJECTIVES: To provide physicians with current guidelines for the diagnosis and optimal management of asthma in children and adults, including pregnant women and the elderly, in office, emergency department, hospital and clinic settings. OPTIONS: The consensus group considered the roles of education, avoidance of provocative environmental and other factors, diverse pharmacotherapies, delivery devices and emergency and in-hospital management of asthma. OUTCOMES: Provision of the best control of asthma by confirmation of the diagnosis using objective measures, rapid achievement and maintenance of control and regular follow-up. EVIDENCE: The key diagnostic and therapeutic recommendations are based on the 1995 Canadian guidelines and a critical review of the literature by small groups before a full meeting of the consensus group. Recommendations are graded according to 5 levels of evidence. Differences of opinion were resolved by consensus following discussion. VALUES: Respirologists, immunoallergists, pediatricians and emergency and family physicians gave prime consideration to the achievement and maintenance of optimal control of asthma through avoidance of environmental inciters, education of patients and the lowest effective regime of pharmacotherapy to reduce morbidity and mortality. BENEFITS, HARMS AND COSTS: Adherence to the guidelines should be accompanied by significant reduction in patients'' symptoms, reduced morbidity and mortality, fewer emergency and hospital admissions, fewer adverse side-effects from medications, better quality of life for patients and reduced costs. RECOMMENDATIONS: Recommendations are included in each section of the report. In summary, after a diagnosis of asthma is made based on clinical evaluation, including demonstration of variable airflow obstruction, and contributing factors are identified, a treatment plan is established to obtain and maintain optimal asthma control. The main components of treatment are patient education, environmental control, pharmacotherapy tailored to the individual and regular follow-up. VALIDATION: The recommendations were distributed to the members of the Canadian Thoracic Society Asthma and Standards Committees, as well as members of the board of the Canadian Thoracic Society. In addition, collaborating groups representing the Canadian Association of Emergency Physicians, the Canadian College of Family Physicians, the Canadian Paediatric Society and the Canadian Society of Allergy and Immunology were asked to validate the recommendations. The recommendations were discussed at regional meetings throughout Canada. They were also compared with the recommendations of other similar groups in other countries. DISSEMINATION AND IMPLEMENTATION: An implementation committee has established a strategy for disseminating these guidelines to physicians, other health professionals and patients and for developing tools and means that will help integrate the recommendations into current asthma care. The plan is outlined in this report.     

Ovine fetal development is more sensitive to perturbation by the presence of serum in embryo culture before rather than after compaction

The effects on subsequent fetal development of the presence or absence of serum at different times during IVC of ovine zygotes were studied. Zygotes, recovered from superovulated ewes 36h after intrauterine AI using semen from a single sire, were cultured for 5 days in synthetic oviductal fluid (SOF) media supplemented with either BSA and amino acids (SOF-) or with 10% (v/v) steer serum (SOF+). Serum was present or absent during the first two and last 2 days of IVC giving four treatments (SOF-/SOF-; SOF-/SOF+;SOF+/SOF- and SOF+/SOF+). In total, 224 embryos, including 26 in vivo controls, were transferred singly at day 6 post-AI to synchronous recipients and the products of conception recovered at day 125 of gestation. Presence of serum during IVC had a biphasic effect on embryo development. The inclusion of serum during the first 2 days of IVC retarded early embryo development while the inclusion of serum during the last 2 days of IVC produced more blastocysts by day 6. These effects were independent of each other. The presence of serum during the first 2 days of IVC resulted in increased weights of gravid uterus, placenta, fetus, fetal heart and liver. The incidence of fetuses whose total or organ weights were greater than three standard deviations above the corresponding mean weights of control fetuses was also greater when serum was present during the first 2 days of IVC. However, even when serum was absent throughout IVC there was still an infrequent incidence of fetal weights greater than three standard deviations above the mean for control fetuses. These observations provide evidence that it is the early pre-compaction stages of embryo development that are particularly sensitive to perturbations leading to abnormal fetal development.