[Peroperative anesthesiologic management and neuro-monitoring of patients with subarachnoid hemorrhage].
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Anesthesia↗
Biomedical subjects
L Dumont
Publications and source records attributed to L Dumont.
Prolongation of rat heart allograft survival with K(+)ATP-dependent channel modulators.
Controversies exist regarding the immunoregulatory properties of K(+) ATP channel modulators. We investigated the effects of aprikalim, a K(+) ATP-dependent channels activator, and glibenclamide and gliclazide, two inhibitors of K(+) ATP-dependent channels, on the prolongation of heart allograft survival in the rat. Nine groups (n >/= 5) were involved in this study with the Brown-Norway to Lewis rat combination treated with aprikalim, glibenclamide, gliclazide, and/or cyclosporine. The results indicate that modulators of K(+) ATP-dependent channels can improve the survival of rat heart allograft without interfering with the immunosuppressive properties of cyclosporine.
Animals↗
Cardioprotective efficacy of verapamil and mibefradil in young UM-X7.1 cardiomyopathic hamsters.
Since calcium overload and increased in T-type calcium channel activity have been observed in the cardiomyopathic (CM) hamster, we hypothesized that mibefradil (Ro 40-5967), a new T- and L-type calcium channel blocker, may exert significant cardioprotection in the early phase of the disease. Young (30-day-old) CM hamsters of the UM-X7.1 subline were treated with mibefradil or verapamil for 4 to 6 weeks. Mibefradil doses were in the range of 0.5 to 8 mg/kg/day while verapamil was given at a dose of 5-10 mg/kg/day, both drugs being injected twice daily (s.c. and i.p. alternatively). At the end of the treatment period, myocardial and skeletal muscle (tongue) were harvested and processed for assessment of necrotic changes and calcification. In hearts from control CM hamsters, numerous necrotic and calcified foci were observed. These myocardial necrosis markers were not attenuated by mibefradil in the dose range studied whereas verapamil significantly reduced their severity. The dystrophic process in skeletal muscle (tongue) was not inhibited by mibefradil or verapamil. These results suggest that mechanisms other than inhibition of T- and L-type calcium channels are related to the cardioprotection observed in the presence of verapamil. A specific action on the sarcoplasmic reticulum (ryanodine-sensitive calcium channel) or the mitochondria may explain the efficacy of phenylalkylamines (verapamil) in this condition.
Animals↗
Quality and clinical response to transfusion of prestorage white cell-reduced apheresis platelets prepared by use of an in-line white cell-reduction system.
BACKGROUND: This study evaluated the quality and clinical effectiveness of white cell (WBC)-reduced apheresis platelets collected by the use of a new technology, fluidized particle-bed separation. STUDY DESIGN AND METHODS: In phase 1, six suitable donors underwent two separate plateletpheresis procedures on one occasion, each separated by less than 10 minutes. In random order, a control unit was collected with the COBE Spectra and a test unit with the Spectra Leukocyte-Reduction System (LRS). The quality of apheresis platelet components was assessed by an in vitro test panel, and residual WBCs were counted by Nageotte chamber and flow cytometric methods. For the in vivo studies, the test and control units were randomly labeled with either 51Cr or 111In at the end of storage and transfused simultaneously to the donor. Samples were taken for calculation of platelet survival and recovery. In phase II, 109 thrombocytopenic patients were given platelets collected by use of the Spectra LRS. RESULTS: Test platelets had significantly fewer residual WBCs (median 7.6 x 10(4)) than control platelets (median 3.9 x 10(5)), with equivalent in vitro function values. Test and control platelets had similar recovery and survival. Transfused platelets collected by use of the LRS achieved a mean 1-hour corrected-count increment of 19.3. CONCLUSION: The LRS collects platelet components with significantly lower WBC contamination without adverse effects on the function or in vivo survival of the platelets.
Blood Platelets↗
Anti-L-selectin antibody treatment of hemorrhagic-traumatic shock in baboons.
OBJECTIVES: The adhesion molecule L-selectin plays an important role in leukocyte-endothelium interactions, thereby contributing to inflammatory reactions. We tested the hypothesis that humanized anti-L-selectin antibodies reduce trauma-associated organ damage and mortality. DESIGN: Prospective, randomized experimental study. SETTING: Independent nonprofit research laboratory in a trauma hospital (Ludwig Boltzmann Institute) and a contract research institute (Biocon). SUBJECTS: Twenty-eight male baboons (Papio ursinus), 18 to 29 kg. INTERVENTIONS: Hemorrhagic-traumatic shock was created by complement activation with cobra venom factor, followed by withdrawal of blood to a mean arterial pressure of 35 to 45 mm Hg. Blood and lactated Ringer's solution were reinfused. Animals were randomized to receive either 2 mg/kg humanized anti-L-selectin antibody (HuDREG-55 [Ab]) or placebo (lactated Ringer's solution [LRS]). MEASUREMENTS AND MAIN RESULTS: Treatment with humanized anti-L-selectin antibody decreased mortality (Ab 21% vs. LRS 71%; p = .011) and improved survival time (p = .016). A trend toward reduced organ damage, especially in the adrenal glands (score 1.2 +/- 0.2 placebo vs. 1.0 +/- 0.1 antibody; p = .059) was seen, and at 24 hrs was accompanied by significantly increased mean arterial pressure (Ab 99 +/- 6 mm Hg vs. LRS 79 +/- 8 mm Hg; p = .023), cardiac output (Ab 3.4 +/- 0.2 L/min vs. LRS 2.4 +/- 0.3 L/min; p = .007), core temperature (p = .048), and improved perfusion, with less negative base excess (Ab 2.9 +/- 1.1 vs. LRS 2.1 +/- 1.7; p = .019) and a trend toward less lactate (p = .065). These improvements were accompanied by significantly (p = .006) decreased fluid requirements in the treatment group (Ab 11.7 +/- 2.5 mL/kg/hr vs. LRS 23.0 +/- 2.3 mL/kg/hr). There were also fewer circulating leukocytes (p = .042) in the treatment group at 24 hrs. CONCLUSION: Humanized anti-L-selectin antibody has beneficial effects on survival in a long-term in vivo model of hemorrhagic. traumatic shock.
Animals↗
Effects of the 21-aminosteroid U74389G in a model of chronic myocardial infarction in the rat.
21-Aminosteroids are a group of new synthetic compounds developed as antiperoxidants. Although several studies have demonstrated their cardioprotective properties in acute ischemic models, none has assessed their long-term benefits after chronic myocardial infarction. In this investigation, we examined the cardioprotective effects of U74389G, a novel 21-aminosteroid, in a model of chronic myocardial infarction in the rat. After permanent ligation of the proximal branch of the left coronary artery, the experimental animals were treated daily by gavage with U74389G (10 mg/kg) for 21 days. After the study period, harvested hearts were perfused ex vivo and submitted to cold cardioplegia with 90-min global ischemia and 30-min reperfusion (surgical stress). Myocardial function and coronary endothelial (bradykinin, 1 microM) and smooth muscle (sodium nitroprusside, 1 microM) reactivity were assessed before and after exposure to the surgical stress. Percentage infarct size of the left ventricle was computed as the ratio of infarct area (mg)/total left ventricle (mg) x 100. During or immediately after surgery, there were eight deaths, which were considered technical failures. No further deaths occurred during the follow-up period (21 days). Compared with vehicle-treated rats, long-term administration of U74389G elicited a significant reduction of infarct size (percentage of left ventricle, 9 +/- 5% in the U74389G-treated group vs. 32 +/- 5% in the vehicle-treated group; p < 0.01). Ex vivo heart-perfusion studies showed no significant difference in baseline coronary flow, left ventricular developed pressure, and heart rate between normal and chronic infarcted hearts treated with the vehicle or with U74389G. However, a reduced endothelium-dependent coronary dilator response was observed in infarcted hearts from vehicle-treated controls but not in those from U74389G-treated rats. When cardioplegia and global myocardial ischemia/reperfusion were added, most of the benefits from U74389G were lost. These results indicate that 21-aminosteroids can reverse oxygen-derived free radicals and lipid peroxidation-induced myocardial and coronary dysfunction associated with chronic myocardial infarction. However, additive protective measures are required when an acute ischemic stress is superimposed.
Animals↗
Brain magnetic resonance imaging (MRI) and neurological changes after a single high altitude climb.
PURPOSE: Neurological impairment, mental dysfunction, and brain imaging changes caused by severe hypoxia have been described by several authors. However, the occurrence of transitory, long lasting, or permanent brain damage has been debated. Although climbing to 8000 m is reserved to a small number of climbers, there are hundreds of lowlanders spending relatively short holidays climbing peaks up to 6000 m in the Andes or in the Himalayas. They are usually not well acclimated and often suffer from acute mountain sickness (AMS). The aim of this study was to examine the effect of a single high altitude exposure on the changes in brain MRI and neuropsychological testing in climbers. METHODS: Brain MRI, medical history, and a battery of neuropsychological tests were obtained in eight male climbers between 31 and 48 yr of age a few days before and between 5 and 10 d after returning to sea level following ascent to altitudes of over 6000 m without oxygen. RESULTS: The mean AMS symptom score recorded at 5500 m was three in all climbers, headache being the predominant symptom. CONCLUSION: We did not observe the changes in brain imaging and in neuropsychological testing observed by other authors. The residual central nervous system impairment following return from high altitude was not observed in our study, and the good results in neuropsychological testing were well correlated with the unchanged brain MRI imaging.
Adult↗
Immunomodulating effects of second-generation calcium channel blockers on experimental heart transplantation.
The administration of second-generation calcium channel blockers (CCBs) to counteract the adverse effects of conventional immunosuppression gains more and more acceptance. Since these newly developed molecules differ in their chemical structure and possess specific pharmacokinetic profiles, we hypothesized that exposure to clinically relevant concentrations may have a significant immunomodulatory potential. The effects of various second-generation CCBs, felodipine, amlodipine, mibefradil and clentiazem, on cardiac allograft survival were therefore evaluated. Inbred male Lewis rats were used as recipients and Brown-Norway rats as donors. After abdominal implantation of the donor heart, allograft recipients were exposed to felodipine (31 microg/kg/day), amlodipine (25 microg/kg/day), mibefradil (3 mg/kg/day) or clentiazem (2.5 mg/kg/day). Other allograft recipients were treated with low-dose cyclosporine (CsA) alone (2 mg/kg/day) or with low-dose CsA combined with amlodipine (25 microg/kg/day), mibefradil (3 mg/kg/day) or clentiazem (2.5 mg/kg/day). All drugs were given daily by gavage. Median survival time of untreated cardiac allografts was 6.5 days. When given alone, not all the second-generation CCBs elicited a positive effect: the dihydropyridines felodipine and amlodipine were ineffective (median survival time was 6.5 and 7.0 days, respectively), the T- and L-type CCB mibefradil had a significant but minor impact (median survival time = 9.0 days, p <0.0015) while the benzothiazepine clentiazem produced the most significant result (median survival time = 16.0 days, p <0.0033). Neither amlodipine nor mibefradil modified the extent of survival provided by low-dose CsA (median survival time = 9.0 days), while clentiazem had a significant positive effect. These data indicate that second-generation CCBs differ in their immunomodulatory potential. These observations of pharmacodynamic specificity appear to be related to differences in their chemical structure as well as their interaction with other sites than the calcium channel.
Adjuvants, Immunologic↗
A serious anaesthetic complication of a Lefort I osteotomy.
We report a case of surgical transsection of the nasoendotracheal tube during a Lefort I maxillary osteotomy, resulting in severe intra-operative ventilatory difficulties. The management of this problem and a brief review of the literature are presented.
Adolescent↗
Magnesium and acute mountain sickness.
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Acclimatization↗
Two doses of intrathecal sufentanil (2.5 and 5 microg) combined with bupivacaine and epinephrine for labor analgesia.
UNLABELLED: In this study, we evaluated the effect of two doses of intrathecal sufentanil combined with bupivacaine and epinephrine on the incidence of pruritus and on the duration and quality of analgesia. One hundred five parturients were enrolled in this randomized, double-blinded, placebo-controlled study. They received either intrathecal 1.25 mg bupivacaine and 25 microg epinephrine (control group); 1.25 mg bupivacaine, 25 microg epinephrine, and 2.5 microg sufentanil (2.5-microg group); or 1.25 mg bupivacaine, 25 microg epinephrine, and 5 microg (5-microg group). Pain relief was assessed 10 min after injection, and pruritus was recorded at 30 min by a blinded observer. The study ended when the parturients requested further analgesia. There were no demographic differences among groups. Ninety of 103 parturients achieved complete pain relief with the initial dose, 11 patients in the control group (P < 0.004, control versus both sufentanil groups), and 2 patients in the 2.5-microg group needed a supplemental epidural bupivacaine. Pruritus was absent in the control group (P < 0.0001, control versus both sufentanil groups), whereas it was present in 36% of the 2.5-microg group and in 66% of the 5-microg group (P = 0.015, 2.5-microg versus 5-microg group). The mean duration of analgesia was similar in patients receiving sufentanil (2.5-microg group: 133 +/- 55 min; 5-microg group: 142 +/- 52 min) but was significantly higher than the control group (56 +/- 32 min). Reducing the sufentanil dose from 5 microg to 2.5 microg when combined with bupivacaine and epinephrine, decreases the incidence of pruritus without impeding the quality or duration of analgesia. IMPLICATIONS: We evaluated two different doses of intrathecal sufentanil combined with bupivacaine and epinephrine for labor analgesia. Sufentanil 2.5 microg offered an advantage over sufentanil 5 microg because, while providing the same quality and duration of analgesia, it was associated with a reduced incidence of pruritus.
Adult↗
Real-time isoform analysis by two-dimensional chromatography of a monoclonal antibody during bioreactor fermentations.
A humanized monoclonal antibody specific for L-selectin exhibits two distinct isoforms that are distinguishable by a charged group modification on one of the antibody light chains. The added charge allows baseline separation of the isoforms by anion-exchange chromatography. Since this modification most likely results from specific enzymatic activity within the Golgi complex, it is possible that fermentation conditions may affect the relative amounts of the isoforms produced. Herein is described a two-dimensional chromatographic method for quantifying the relative amounts of the isoforms from fermentation broths, in real time.
Antibodies, Monoclonal↗
The H19 TATA-less promoter is efficiently repressed by wild-type tumor suppressor gene product p53.
The developmentally regulated H19 gene displays several remarkable properties: expression of an apparently non-translated mRNA, genomic imprinting (maternal allele only expressed), relaxation of the imprinting and/or epigenetic lesions demonstrated in some tumors. Despite several observations after relaxation of imprinting status of the gene, data on trans and cis-acting factors required for the human H19 gene expression are still missing. As a first approach to address identification of factors involved in the regulation of the gene, we found that cells from a p53 antisense-transfected HeLa clone displayed increased amounts of H19 transcripts when compared to the non-transfected cells. Moreover, a HeLa clone stably transfected with a temperature sensitive (ts) 143 Ala p53 mutant exhibited temperature-dependent regulation of H19 expression. This preliminary indication of the repressing effect of the p53 protein on H19 expression has been confirmed by transient cotransfection experiments in HeLa cells, using luciferase surrogate constructs under the control of the 823 bp sequence immediately upstream of the transcription start point of the H19 gene, and different constructs containing sense, antisense or a ts 143 Ala mutant p53 cDNA. We observed an increase of H19 promoter-driven activity in transient cotransfections with the antisense p53 cDNA and the temperature sensitive mutant p53 at the non-permissive temperature, but a decrease with sense wild-type p53 cDNA. Furthermore, the cotransfection experiments were repeated in a cell line lacking endogenous p53. (Calu 6 cells) and the results provided additional evidence for a down regulation of the expression of the H19 gene by the p53 protein.
Gene Expression Regulation, Neoplastic↗
H19 overexpression in breast adenocarcinoma stromal cells is associated with tumor values and steroid receptor status but independent of p53 and Ki-67 expression.
In a previous study we described the expression of the H19 gene by in situ hybridization (ISH) in normal breast and in benign or malignant breast tumors (Dugimont T, Curgy JJ, Wernert N, Delobelle A, Raes MB, Joubel A, Stehelin D, Coll J: Biol Cell 1995, 85:117-124). In the present work, 1) we extend the previous one to a statistically useful number of adenocarcinomas, including 10 subclasses, 2) we provide information on the precise ISH localization of the H19 RNA by using, on serial tissue sections, antibodies delineating specifically the stromal or the epithelial component of the breast, and 3) we consider relationships between the H19 gene expression and various clinicopathological information as tumor values (T0 to T4), grades, steroid receptors, lymph node status, and molecular features as the p53 gene product and the Ki-67/MIB1 protein, which is specific to proliferating cells. Data indicate that 1) in 72.5% of studied breast adenocarcinomas an overall H19 gene expression is increased when compared with healthy tissues, 2) the H19 gene is generally overexpressed in stromal cells (92.2%) and rarely in epithelial cells (2.9% only), 3) an up-regulation of the H19 gene is significantly correlated with the tumor values and the presence of both estrogen and progesterone receptors, and 4) at the cellular level, the H19 gene demonstrates an independent expression versus accumulation of both the p53 protein and the Ki-67/MIB-1 cell-cycle marker.
Adenocarcinoma↗
Labour analgesia in a patient with carnitine palmityl transferase deficiency and idiopathic thrombocytopenic purpura.
We report a case of a woman with carnitine palmityl deficiency (CPT) and idiopathic thrombocytopenic purpura, presenting in active labour at 38 weeks gestation. We discuss different anaesthetic factors involved with both diseases, and we propose an optimal management of such cases. Neuraxial analgesia with minimal motor blockade is indicated in early labour because it is necessary to alleviate stress in order to avoid rhabdomyolisis associated with CPT deficiency. Neuraxial analgesia is also needed because the theoretical risk of performing a caesarean section is higher than in a normal population, first because labour must be kept as short as possible and secondly because the possible thrombocytopenic in the baby precludes the use of instrumental delivery.
Journal Article↗
Use of remifentanil in a patient with chronic hepatic failure.
We describe a 73-yr-old woman anaesthetized for a laminectomy. She suffered from hepatic failure with mild encephalopathy complicated by several exacerbations associated with sedative and opioid therapy. The challenge for anaesthesia management was to provide adequate analgesia and avoid causing hepatic encephalopathy during and after the surgery. We used remifentanil to provide intraoperative and postoperative analgesia, because it has a short duration of action and does not require hepatic metabolism. We closely monitored the respiratory and the neurological status throughout the administration and conclude that remifentanil can provide perioperative analgesia in patients at risk of developing hepatic encephalopathy.
Aged↗
Effects of phosphoramidon, BQ 788, and BQ 123 on coronary and cardiac dysfunctions of the failing hamster heart.
Coronary dysfunctions identified in the presence of chronic heart failure are an important pathophysiologic abnormality that influences the prognosis of the disease. Because the endothelin pathway plays a significant role in the increased peripheral vascular tone associated with heart failure, we hypothesized that the endothelin pathway may be involved in the abnormal coronary vasomotion associated with this pathologic condition. Experiments were carried out in failing hearts (UM-X7.1 cardiomyopathic hamsters, aged 225-250 days) and normal hearts (Syrian LVG hamsters, also aged 225-250 days). Isolated hearts were perfused at constant flow and exposed to the blocker of the generation of endothelin-1 (ET-1), phosphoramidon (10 microM infusion), as well as to the selective ET(A)-receptor antagonist BQ 123 (10 microM infusion) and to a selective ET(B)-receptor antagonist BQ 788 (1 microM infusion). Coronary and cardiac effects of exogenous ET-1 (0.01-100 pmol) were also studied. Phosphoramidon, BQ 788, and BQ 123 did not altered coronary perfusion pressure either in normal or in failing hearts, whereas cardiac contractility was significantly impaired in the presence of phosphoramidon and BQ 123. Coronary sensitivity to exogenous ET-1 did not demonstrate a significant difference between normal and failing hearts [median effective concentration (EC50), 7 pmol in failing hearts vs. 12 pmol in normal hearts; p = NS]. In the presence of exogenous ET-1, cardiac contractility was significantly increased in both groups. In normal hearts, the exogenous ET-1-induced increase in coronary perfusion pressure was completely antagonized by BQ 123, whereas combined administration of BQ 788 and BQ 123 was necessary to induce complete inhibition in failing hearts. The positive inotropic effect elicited by exogenous ET-1 (EC50) was completely abolished in the presence of BQ 123, whereas BQ 788 had no significant effect. Results indicate that the endothelin pathway does not play a significant role in the altered coronary vasomotion observed in this model of chronic heart failure. On the contrary, the endothelin pathway appears to participate in the maintenance of myocardial contractility. According to these observations, administration of an inhibitor of ET-1 synthesis, as well as the use of an ET(A)-receptor antagonist, may be contraindicated in the presence of poor left ventricular function because the endothelin pathway contributes significantly to the maintenance of cardiac contractility.
Animals↗
Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia.
Humanized anti-CD33 monoclonal antibody HuM195 specifically targets myeloid leukemias in vivo and has been shown to produce molecular remissions in patients with acute promyelocytic leukemia who are in clinical remission. Previous human trials have used low intermittent dosing of HuM195 at 3 mg/m2/day, which is adequate to saturate all available CD33 sites in vivo. In the current trial, we investigated supersaturating doses of HuM195. Ten patients with relapsed or refractory myelogenous leukemia (nine acute myelogenous leukemias and one chronic myelogenous leukemia) were treated on days 1-4 and 15-18 with a 4-h daily infusion of HuM195 at three different dose levels: 12, 24, and 36 mg/m2/day. The total maximum dose of HuM195 was 576 mg. The most common toxicities were grade II fever and rigors, seen more frequently at the highest dose. Interestingly, a transient and reversible drop in hemoglobin of 1-3 g/dl was seen during the infusion in several patients. Flow cytometric analysis showed that antigen sites in the peripheral blood and bone marrow (BM) remained saturated with HuM195 during the entire 4-week trial period. At these high doses, the average plasma half-life of HuM195 was approximately 1 week, compared to 38 h, seen in previous studies. Human anti-HuM195 immune responses were not observed. One patient with acute myelogenous leukemia, whose disease was refractory to two rounds of chemotherapy, with < 10% blasts in his BM, achieved a complete remission, lasting > 32 months, at the first dose level. Another three patients showed a reduction in leukemic BM cells. These studies suggest that high doses of HuM195 achieve a long serum half-life, with tolerable toxicity and without immunogenicity. In addition, antileukemic activity was seen.
Adult↗