Preoperative and postoperative L-lactatemia assessment for the prognosis of right abomasal disorders in dairy cattle.

BACKGROUND: Preoperative L-lactatemia and heart rate have been suggested as prognostic indicators of outcome for cows with right dilatation of the abomasum or volvulus (RDA/AV). However, postoperative L-lactatemia has not been assessed as a potential prognostic tool. OBJECTIVES: To determine the prognostic value of postoperative L-lactatemia (LAC2 ), duration of treatment (Dt), relative L-lactatemia difference (compared with preoperative L-lactatemia [LAC1 ]) ([LAC2 - LAC1 ]/LAC2 ) and change in L-lactate over time ([LAC2 - LAC1 ]/Dt) as compared to preoperative findings (LAC1 and heart rate [HR]) as prognostic factors in dairy cows with RDA/AV. ANIMALS: A total of 41 dairy cows were included: 19 with AV and 22 with RDA; 11 cows had a negative outcome (NO) and 30 cows had a positive outcome (PO) based on telephone follow-up with owners 30 days after surgery. METHODS: Prospective cohort study. Analysis was performed using logistic regression and comparison of area under the receiver operating characteristics curve (AUC) using nonparametric tests. RESULTS: LAC1 > 1.4 mmol/L or LAC2 > 2.2 mmol/L had the same accuracy with sensitivity of 100% (95% CI, 75.1-100%) and specificity of 80% (95% CI, 61.4-92.3%) for predicting NO. The relative L-lactatemia difference ([LAC2 - LAC1 ]/LAC1 ) or lactate kinetics ([LAC2 - LAC1 ]/Dt) were not associated with prognosis. The AUC of the preoperative model (which included HR and lnLAC1 ) was 0.92 (95% CI, 0.83-1.0) and that of the postoperative model (including only lnLAC2 ) was 0.95 (95% CI, 0.88-1.0); these were not significantly different. CONCLUSIONS AND CLINICAL IMPORTANCE: Postoperative L-lactatemia is helpful to predict outcome in cows with RDA/AV. The short-term change in blood L-lactate is not a useful prognostic indicator, at least during the period of time spent on the farm for surgery and treatment.

Preoperative cow-side lactatemia measurement predicts negative outcome in Holstein dairy cattle with right abomasal disorders.

The objectives of the current study were (1) to determine the gain in prognostic accuracy of preoperative l-lactate concentration (LAC) measured on farm on cows with right displaced abomasum (RDA) or abomasal volvulus (AV) for predicting negative outcome; and (2) to suggest clinically relevant thresholds for such use. A cohort of 102 cows with on-farm surgical diagnostic of RDA or AV was obtained from June 2009 through December 2011. Blood was drawn from coccygeal vessels before surgery and plasma LAC was immediately measured by using a portable clinical analyzer. Dairy producers were interviewed by phone 30 d following surgery and the outcome was determined: a positive outcome if the owner was satisfied of the overall evolution 30 d postoperatively, and a negative outcome if the cow was culled, died, or if the owner reported being unsatisfied 30 d postoperatively. The area under the curve of the receiver operating characteristic curve for LAC was 0.92 and was significantly greater than the area under the curve of the receiver operating characteristic curve of heart rate (HR; 0.77), indicating that LAC, in general, performed better than HR to predict a negative outcome. Furthermore, the ability to predict a negative outcome was significantly improved when LAC measurement was considered in addition to the already available HR data (area under the curve: 0.93 and 95% confidence interval: 0.87, 0.99). Important inflection points of the misclassification cost term function were noted at thresholds of 2 and 6 mmol/L, suggesting the potential utility of these cut-points. The 2 and 6 mmol/L thresholds had a sensitivity, specificity, positive predictive value, and negative predictive value for predicting a negative outcome of 76.2, 82.7, 53.3, and 93.1%, and of 28.6, 97.5, 75, and 84%, respectively. In terms of clinical interpretation, LAC ≤2 mmol/L appeared to be a good indicator of positive outcome and could be used to support a surgical treatment decision. The treatment decision for cows with LAC between 2 and 6 mmol/L, however, would depend on the economic context and the owner's attitude to risk in regard to potential return on its investment. Finally, performing a surgical correction on commercial cows with RDA or AV and a LAC ≥6 mmol/L appeared to be unjustified and these animals should be culled based on their high probability of negative outcome.

Molecular determinants of TRP channel assembly.

Calcium channels play important roles in cellular signalling. TRP (transient receptor potential) channels form a superfamily of calcium channels through which Ca(2+) enters the cell. TRPs have six transmembrane segments with a putative pore between the fifth and the sixth segments, and assemble in tetrameric complexes to form functional Ca(2+) channels. They are thus similar to K(V) (voltage-gated potassium channel) channels in terms of structure and molecular determinants that promote subunit assembly. In this review, the molecular determinants mediating the assembly of Drosophila TRP, TRPC (TRP canonical), TRPV (TRP vanilloid) and K(V) channels are described.

Endoscopic screening for esophageal squamous-cell carcinoma in high-risk patients: a prospective study conducted in 62 French endoscopy centers.

BACKGROUND AND STUDY AIMS: The prevalence of esophageal squamous-cell carcinoma in high-risk patients and the advantages of systematic Lugol staining during esophagoscopy have not yet been evaluated in a large prospective study. In this study we aimed to assess the prevalence of this type of tumor in high-risk patients, to examine the role of Lugol staining in endoscopic screening for esophageal squamous-cell carcinoma, and to establish whether it is possible to identify a particularly high-risk group which would benefit from systematic screening. PATIENTS AND METHODS: A prospective study was undertaken in 62 endoscopy centers. A total of 1095 patients were enrolled, none of whom had any esophageal symptoms. These patients had presented with either a past history of or a recent head and neck or tracheobronchial squamous-cell carcinoma (group 1), with alcoholic chronic pancreatitis (group 2), with alcoholic cirrhosis (group 3), or were alcohol and tobacco addicts (group 4). The patients underwent a meticulous endoscopic examination of the esophagus, followed by Lugol staining. RESULTS: The prevalence of esophageal squamous-cell carcinoma was 3.2 %. The group 1 patients showed the highest prevalence of carcinoma (5.3 %) and the highest prevalence of dysplasia (4.5 %). Of the 35 carcinomas detected in the 1095 patients, seven (20 %) were early lesions, and 20 % were only detected after Lugol staining (P = 0.02). High-grade dysplasia was only observed in group 1 patients and two-thirds of these lesions were only diagnosed after Lugol staining. The overall prevalence of low-grade dysplasia was 2.4 %, and 77 % of these were detected only after Lugol staining (P < 0.001). CONCLUSIONS: Lugol dye staining increases the sensitivity of esophageal endoscopy for the detection of high-grade dysplasia and cancer. The prevalence of dysplasia and cancer reached 9.9 % in group 1, and we therefore believe that an endoscopic screening program could be justified for patients with head and neck or tracheobronchial cancer.

[Anesthesic practices in patients with severe postpartum hemorrhage with persistent or worsening bleeding]. / Prise en charge anesthésique en cas d'hémorragie du post-partum qui persiste ou qui s'aggrave malgré les mesures initiales.

Severe postpartum hemorrhage (PPH) is a rare and critical situation which requires fast and well-planned management where close collaboration between obstetricians and anesthesiologists is essential. In case of persisting or worsening bleeding in spite of initially adequate management, the main goal of the anesthesiologist is to maintain hemodynamic stability (fluid resuscitation, transfusion, vasoactive drugs) and optimal respiratory state (oxygenation) and to correct the frequent clotting disorders, whereas the obstetrician and/or the radiologist have to achieve definitive hemostasis. Assessment of the severity of PPH is determined from: quantity of blood loss and/or duration of bleeding, difficulty in maintaining a correct hemodynamic state in spite of active vascular fluid resuscitation, need for vasoactive therapy and transfusion, occurrence and worsening of clotting disorders. Continuous drip Sulprostone requires close clinical surveillance and continuous monitoring (electrocardiography, non-invasive blood pressure monitor, pulse oximetry). When this treatment does not enable sufficiently rapid control of the bleeding (consensus = within 30 minutes), invasive therapy (arterial embolization, vascular ligation even hysterectomy) should be started promptly. When the bleeding continues despite aggressive medical treatments, general anesthesia (even if an epidural catheter is already in place) is needed to proceed with the invasive surgical procedure. This anaesthesia of a "full stomach" patient justifies a rapid-sequence induction with cricoid pressure and intubation. The risk is particularly high in case of hemorrhagic shock. Angiographic embolization should be carried out in an angiography suite which must be equipped for this kind of situation (anesthesia and resuscitation material, adapted monitoring). A member of the anesthesia team must be present throughout this procedure. At best, a multidisciplinary team, specially trained for this purpose, including obstetrician, anesthesiologist, radiologist and biologist should be available. When one or several invasive treatments were necessary to control the bleeding, it is recommended to transfer the patient to a specialized unit (intensive care unit or recovery room).

Ca(2+)-calmodulin regulates receptor-operated Ca(2+) entry activity of TRPC6 in HEK-293 cells.

Mammalian homologues of the Drosophila transient receptor potential channel (TRPC) are involved in Ca(2+) entry following agonist stimulation of nonexcitable cells. Seven mammalian TRPCs have been cloned but their mechanisms of activation and/or regulation are still the subject of intense research efforts. It has already been shown that calmodulin (CaM) can regulate the activity of Drosophila TRP and TRPL and, more recently, CaM has been shown to interact with mammalian TRPCs. In this study, TRPC6 stably transfected into HEK-293 cells was used to investigate the possible influence of CaM on TRPC6-dependent Ca(2+) entry. Overexpression of TRPC6 in mammalian cells is known to enhance agonist-induced Ca(2+) entry, but not thapsigargin-induced Ca(2+) entry. Here, we show that CaM inhibitors (calmidazolium and trifluoperazine) abolish receptor-operated Ca(2+) entry (ROCE) without affecting thapsigargin-operated Ca(2+) entry and that the activity of CaM is dependent on complexation with Ca(2+). We also show that Ca(2+)-CaM binds to TRPC6 and that the binding can be abolished by CaM inhibitors. These results indicate that CaM is involved in the modulation of ROCE.

Dose of prophylactic intravenous ephedrine during spinal anesthesia for cesarean section.

STUDY OBJECTIVE: To compare the incidence of maternal hypotension associated with spinal anesthesia for cesarean section when 10-, 15-, or 20-mg prophylactic boluses of intravenous (IV) ephedrine are used. DESIGN: Prospective observational study. SETTING: Teaching hospital. PATIENTS: 108 women admitted for elective cesarean section. INTERVENTIONS: Spinal anesthesia was performed using hyperbaric bupivacaine 10 mg, sufentanil 2 microg, and morphine 0.2 mg (volume 4 mL). Ephedrine (10, 15, or 20 mg) was administered 2 minutes after the intrathecal injection. Maternal blood pressure was checked every 2 minutes. Hypotension was promptly treated with 5-mg ephedrine boluses. MAIN RESULTS: Incidence of hypotension was significantly higher in women receiving a 10-mg prophylactic dose of ephedrine than in those receiving either a 15-mg or a 20-mg prophylactic dose of ephedrine [23/36 in the 10-mg ephedrine group vs. 13/36 and 10/36 in the 15-mg and 20-mg ephedrine groups, respectively (p< 0.05)]. CONCLUSION: In the conditions of this study, a single bolus of IV ephedrine with doses of either 15 or 20 mg decreased significantly the incidence of maternal hypotension as compared to a single 10-mg bolus of ephedrine.

Most central nervous system D2 dopamine receptors are coupled to their effectors by Go.

We reported previously that Go-deficient mice develop severe neurological defects that include hyperalgesia, a generalized tremor, lack of coordination, and a turning syndrome somewhat reminiscent of unilateral lesions of the dopaminergic nigro-striatal pathway. By using frozen coronal sections of serially sectioned brains of normal and Go-deficient mice, we studied the ability of several G protein coupled receptors to promote binding of GTPgammaS to G proteins and the ability of GTP to promote a shift in the affinity of D2 dopamine receptor for its physiologic agonist dopamine. We found a generalized, but not abolished reduction in agonist-stimulated binding of GTPgammaS to frozen brain sections, with no significant left-right differences. Unexpectedly, the ability of GTP to regulate the binding affinity of dopamine to D2 receptors (as seen in in situ [(35)S]sulpiride displacement curves) that was robust in control mice, was absent in Go-deficient mice. The data suggest that most of the effects of the Gi/Go-coupled D2 receptors in the central nervous system are mediated by Go instead of Gi1, Gi2, or Gi3. In agreement with this, the effect of GTP on dopamine binding to D2 receptors in double Gi1 plus Gi2- and Gi1 plus Gi3-deficient mice was essentially unaffected.

Mechanism of capacitative Ca2+ entry (CCE): interaction between IP3 receptor and TRP links the internal calcium storage compartment to plasma membrane CCE channels.

Activation of cells by agents that stimulate inositol trisphoshate (IP3) formation causes, via IP3 receptor (IP3R) activation, the release of Ca2+ from internal stores and also the entry of Ca2+ via plasma membrane cation channels, referred to as capacitative Ca2+ entry or CCE channels. Trp proteins have been proposed to be the unitary subunits forming CCE channels; however, there is no definitive proof for this hypothesis. We have now identified amino acid sequences of a Trp and of an IP3R that interact to form stable complexes. These complexes appear to form in vivo, as evidenced by co-immunoprecipitation of Trp with IP3R and by the fact that expression of the respective interacting sequences modulates development of CCE brought about by store depletion. The finding that a Trp-interacting sequence of IP3R interferes with natural CCE leads us to conclude that Trp proteins are, indeed, structural members of CCE channels. We conclude further that direct coupling of IP3R to Trp is a physiological mechanism by which cells trigger CCE in response to signals that stimulate phosphoinositide hydrolysis and IP3 formation. Pros and cons of various CCE activation models are discussed.

Statistical support for uncertainty in radiological diagnosis.

Radiological interpretation and diagnosis involves the comparison and classification of complex medical images and is typical of the categorisation tasks that have been the subject of observational studies in Cognitive Science. This paper considers the affinity between statistical modelling and theories of categorisation for naturally occurring categories. Statistical based measures of similarity and typicality with a probabilistic interpretation are derived. The utilisation of these measures in the support of diagnosis under uncertainty via interactive overview plots is described. The application of the methodology to magnetic resonance imaging of the head is considered. The methods detailed have application to other fields involving archiving and retrieving of image data.

Effect of injection rate on hypotension associated with spinal anesthesia for cesarean section.

Maternal hypotension is a common problem during cesarean section under spinal anesthesia. We evaluated in a prospective observational study the influence of injection speed on maternal hypotension. Hyperbaric bupivacaine 10 mg, sufentanil 2 microg and morphine 200 microg (total volume 4 mL) were injected either quickly (<15 s) or slowly (=120 s) in 50 women scheduled for elective cesarean section. Hypotension (systolic arterial pressure (SAP) <100 mmHg or <70% of baseline) was promptly treated with 5 mg ephedrine boluses. Slow injection significantly reduced the incidence of hypotension (68% in the 120 s group and 92% in the other, P =0.03). In addition, onset of hypotension was delayed, had a shorter duration and required less ephedrine for hypotension in the 120 s group (11.6 mg vs. 19.6 mg, P =0.019). Anesthesia was satisfactory for all women. We conclude that a 2 mL/min injection rate may be a simple and effective way to reduce the incidence and severity of hypotension during cesarean section under spinal anesthesia.

Structured computer-based training in the interpretation of neuroradiological images.

Computer-based systems may be able to address a recognised need throughout the medical profession for a more structured approach to training. We describe a combined training system for neuroradiology, the MR Tutor that differs from previous approaches to computer-assisted training in radiology in that it provides case-based tuition whereby the system and user communicate in terms of a well-founded Image Description Language. The system implements a novel method of visualisation and interaction with a library of fully described cases utilising statistical models of similarity, typicality and disease categorisation of cases. We describe the rationale, knowledge representation and design of the system, and provide a formative evaluation of its usability and effectiveness.

Central venous catheter placement in children: evaluation of electrocardiography using J-wire.

Misplacement of a central venous catheter may lead to myocardial perforation and dysrhythmia. Atrial electrocardiography (ECG) through a saline column is an effective but complex method to determine the accurate location of catheters. We evaluated a simplified variant of this technique using the guidewire as an internal electrode in 23 children (5-16 years old) undergoing spinal surgery. Catheters were placed using a Seldinger technique after jugular or subclavian venous puncture. Each time the operator recognized the atrial signal, the catheter was found to be correctly placed on the chest radiograph (20/23). In three patients, the atrial signal was not obtained. A technical error was responsible in one case whereas the two others were related to aberrant migrations of the catheter either into a subclavian vein or into the pleura. In this latter case, the complication was unrecognized on the first radiograph despite malposition having been predicted by atrial ECG. We conclude that a method using atrial ECG guidance is sensitive and specific, and may be an alternative to the classical chest radiograph to detect accurate placement of central venous catheters in children.

Modulation of Ca(2+) entry by polypeptides of the inositol 1,4, 5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): evidence for roles of TRP and IP3R in store depletion-activated Ca(2+) entry.

Homologues of Drosophilia transient receptor potential (TRP) have been proposed to be unitary subunits of plasma membrane ion channels that are activated as a consequence of active or passive depletion of Ca(2+) stores. In agreement with this hypothesis, cells expressing TRPs display novel Ca(2+)-permeable cation channels that can be activated by the inositol 1,4,5-trisphosphate receptor (IP3R) protein. Expression of TRPs alters cells in many ways, including up-regulation of IP3Rs not coded for by TRP genes, and proof that TRP forms channels of these and other cells is still missing. Here, we document physical interaction of TRP and IP3R by coimmunoprecipitation and glutathione S-transferase-pulldown experiments and identify two regions of IP3R, F2q and F2g, that interact with one region of TRP, C7. These interacting regions were expressed in cells with an unmodified complement of TRPs and IP3Rs to study their effect on agonist- as well as store depletion-induced Ca(2+) entry and to test for a role of their respective binding partners in Ca(2+) entry. C7 and an F2q-containing fragment of IP3R decreased both forms of Ca(2+) entry. In contrast, F2g enhanced the two forms of Ca(2+) entry. We conclude that store depletion-activated Ca(2+) entry occurs through channels that have TRPs as one of their normal structural components, and that these channels are directly activated by IP3Rs. IP3Rs, therefore, have the dual role of releasing Ca(2+) from stores and activating Ca(2+) influx in response to either increasing IP3 or decreasing luminal Ca(2+).

Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ entry channel.

Capacitative Ca2+ entry (CCE) is Ca2+ entering after stimulation of inositol 1,4,5-trisphosphate (IP3) formation and initiation of Ca2+ store depletion. One hallmark of CCE is that it can also be triggered merely by store depletion, as occurs after inhibition of internal Ca2+ pumps with thapsigargin. Evidence has accumulated in support of a role of transient receptor potential (Trp) proteins as structural subunits of a class of Ca2+-permeable cation channels activated by agonists that stimulate IP3 formation-very likely through a direct interaction between the IP3 receptor and a Trp subunit of the Ca2+ entry channel. The role of Trp's in Ca2+ entry triggered by store depletion alone is less clear. Only a few of the cloned Trp's appear to enhance this type of Ca2+ entry, and when they do, the effect requires special conditions to be observed, which native CCE does not. Here we report the full-length cDNA of mouse trp2, the homologue of the human trp2 pseudogene. Mouse Trp2 is shown to be readily activated not only after stimulation with an agonist but also by store depletion in the absence of an agonist. In contrast to other Trp proteins, Trp2-mediated Ca2+ entry activated by store depletion is seen under the same conditions that reveal endogenous store depletion-activated Ca2+ entry, i.e., classical CCE. The findings support the general hypothesis that Trp proteins are subunits of store- and receptor-operated Ca2+ channels.

The story of the internal carotid artery of mammals: from Galen to sudden infant death syndrome.

Some anatomical aspects of the blood supply of the brains of mammals have been examined to illuminate their functions. A fundamental explanation of sudden infant death syndrome (cot death) is suggested following experimental observations. Speculative contributions have been made to comparative physiological ideas concerning mammals of pronograde and erect habitus, their vascular pressure adaptations and temperature management. Neuro- and interventional radiologists may make some significant future applications of these ideas. Of immediate practical interest is the possibility of influencing the well-being of human embryos' neural tube development in utero by a comprehensive study of their temperature environment.

[Acute cardiogenic postoperative edema after doxorubicin (adriamycin) chemotherapy]. / Oedème aigu du poumon cardiogénique postopératoire après chimiothérapie par doxorubicine (adriamycine).

We describe a case of postoperative congestive heart failure in a young woman of physical class ASA 1, following breast cancer surgery. Preoperatively she had been treated with doxorubicin (Adriamycin) 450 mg.m-2, total dose, associated with breast and ovarian radiotherapy. This association was probably the cause of postoperative heart failure. Twenty-four hours after surgery, a two-dimensional echocardiography showed a severe left ventricular dysfunction, whereas preoperative clinical assessment was unremarkable. Doxorubicin cardiotoxicity can be acute, subacute and delayed as in our case. Clinical assessment and ECG are not sensitive indicators of such cardiac damage. Preoperative echography is the technique of choice for the evaluation of the cardiac status of a patient treated with a high cumulative dose of doxorubicin and mediastinal irradiation.

Multiple neurological abnormalities in mice deficient in the G protein Go.

The G protein Go is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, alpha2-adrenergic, M2 muscarinic, and somatostatin receptors. In vitro, Go is also activated by growth cone-associated protein of Mr 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that Go may play in intact cells and whole body homeostasis, we disrupted the gene encoding the alpha subunits of Go in embryonic stem cells and derived Go-deficient mice. Mice with a disrupted alphao gene (alphao-/- mice) lived but had an average half-life of only about 7 weeks. No Goalpha was detectable in homogenates of alphao-/- mice by ADP-ribosylation with pertussis toxin. At the cellular level, inhibition of cardiac adenylyl cyclase by carbachol (50-55% at saturation) was unaffected, but inhibition of Ca2+ channel currents by opioid receptor agonist in dorsal root ganglion cells was decreased by 30%, and in 25% of the alphao-/- cells examined, the Ca2+ channel was activated at voltages that were 13.3 +/- 1.7 mV lower than in their counterparts. Loss of alphao was not accompanied by appearance of significant amounts of active free betagamma dimers (prepulse test). At the level of the living animal, Go-deficient mice are hyperalgesic (hot-plate test) and display a severe motor control impairment (falling from rotarods and 1-inch wide beams). In spite of this deficiency, alphao-/- mice are hyperactive and exhibit a turning behavior that has them running in circles for hours on end, both in cages and in open-field tests. Except for one, all alphao-/- mice turned only counterclockwise. These findings indicate that Go plays a major role in motor control, in motor behavior, and in pain perception and also predict involvement of Go in Ca2+ channel regulation by an unknown mechanism.

Ionic currents underlying HTRP3 mediated agonist-dependent Ca2+ influx in stably transfected HEK293 cells.

hTrp3 is a human homologue of the Drosophila gene responsible for a transient receptor potential (trp) mutation. When stably expressed in HEK293 cells, hTrp3 formed ion channels that were active under resting conditions but could be further stimulated by carbachol or ATP via endogenous muscarinic or purinergic receptors, respectively. Agonist evoked currents reversed polarity near 0 mV in physiological ionic conditions and were associated with a significant increase in the current variance. These results suggest the involvement of a non-selective cation channel with relatively large unitary amplitude. Consistent with this, resolved unitary events had a conductance of approximately 60 pS in the negative voltage range and an extrapolated reversal potential near 0 mV.