Perioperative management of severe head injury in a patient with arrhythmogenic right ventricular dysplasia.
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Accidents, Traffic↗
Biomedical subjects
J Marty
Publications and source records attributed to J Marty.
Out-of-hospital thrombolytic therapy during cardiopulmonary resuscitation in refractory cardiac arrest due to acute myocardial infarction.
Out-of-hospital thrombolytic therapy was administrated to a 53-year-old woman with confirmed acute myocardial infarction and refractory cardiac arrest. Standard advanced cardiac life support measures were performed by an out-of-hospital critical care team but they were unsuccessful. Thrombolytic therapy was given as a rescue therapy after prolonged cardiopulmonary resuscitation. The patient recovered a sinus rhythm and circulation 20 minutes after a bolus infusion of tissue plasminogen activator and was fit to be transported to the hospital. Reversal of arterial occlusion was confirmed at the hospital. There was no sequelae related to thrombolytic therapy and the patient was finally discharged 21 days later. This is the first published report of out-of-hospital thrombolytic therapy during cardiopulmonary resuscitation for a patient with refractory cardiac arrest due to acute myocardial infarction.
Ambulatory Care↗
Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.
Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II clinical trials in cancer patients. To broaden our understanding of the clinical potential for squalamine, this agent was evaluated in nu/nu mouse xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines. Squalamine was studied alone and in combination with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that was better than cisplatin alone. Squalamine also significantly enhanced the activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model. Squalamine similarly improved the effectiveness of cisplatin in producing TGI when screened against the SD human neuroblastoma xenograft. Xenograft tumor shrinkage was seen for the MV-522 tumor in combination treatments including squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from the treatment regimen. To gain a greater understanding of the mechanism by which squalamine inhibited tumor growth in the xenograft studies, in vitro experiments were carried out with vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in culture exposed to squalamine. Squalamine treatment was found to retard two cellular events necessary for angiogenesis, inducing disorganization of F-actin stress fibers and causing a concomitant reduction of detectable cell the surface molecular endothelial cadherin (VE-cadherin). We propose that the augmentation by squalamine of cytotoxicity from platinum-based therapies is attributable to interference by squalamine with the ability of stimuli to promote endothelial cell movement and cell-cell communication necessary for growth of new blood vessels in xenografts after chemotherapeutic injury to the tumor.
Actins↗
Elevated expression of DNA ligase I in human cancers.
PURPOSE: Human DNA ligase I plays an essential role in DNA replication, recombination, and repair by catalyzing the formation of phosphodiester bonds between adjacent 5'-phosphoryl and 3'-hydroxyl termini at single breaks in duplex DNA molecules. DNA ligase I is responsible for the majority of DNA ligase activity present in proliferating cells among four different forms of DNA ligases, designated DNA ligase I, II, III, and IV. In this study, we were interested in comparing DNA ligase I level in human tumors versus normal tissues and in studying whether the inhibition of DNA ligase I could lead to tumor cell death. EXPERIMENTAL DESIGN: DNA ligase I level was measured by Western immunoblot assay in various human malignant tumor specimens and benign tissues obtained from patients, in peripheral blood lymphocytes obtained from healthy donors, and in human tumors grown in nude mice. We also have designed antisense oligonucleotides (ODNs) targeting the mRNA of DNA ligase I and tested whether DNA ligase I antisense ODNs could control tumor cell growth. RESULTS: The amount of DNA ligase I enzyme in malignant tumors was considerably higher than that in benign normal tissues and peripheral blood lymphocytes. The level of DNA ligase I in human tumors grown in nude mice was also very high, and the expression of DNA ligase I appears to be constitutive during in vivo tumor development. We have observed that DNA ligase I antisense ODN inhibited tumor cell growth in a dose-response manner, but nonspecific control ODNs had little effect on the growth of the same cell lines. CONCLUSIONS: The presence of DNA ligase I at higher levels in human tumors than in benign normal tissues and normal peripheral lymphocytes suggests DNA ligase I plays more of a role in proliferating cells than in resting cells. These results, together with our finding that DNA ligase I antisense ODNs can suppress tumor cell proliferation, warrant the design and testing of human DNA ligase I inhibitors as new anticancer agents.
Animals↗
In situ split liver transplantation for two adult recipients.
BACKGROUND: Modifications of the in situ split liver technique are needed for safe transplantation in two adult recipients with a single donor. METHODS: The graft from a brain-dead donor, 187 cm tall and weighing 89 kg, was split in situ with a transection performed along the main portal fissure retaining the middle hepatic vein with the left graft. The right and left grafts, which weighed 985 and 760 g, respectively, were transplanted in two adult recipients weighing 70 and 56 kg, respectively. RESULTS: Both recipients had minor intraoperative blood loss and were discharged from intensive care on day 3. Both grafts were rapidly functional, and the two patients were in excellent condition with normal liver function tests 9 months after surgery. CONCLUSION: In situ split liver transplantation can be performed with the middle hepatic vein retained in the left graft to obtain a sufficient volume of the two grafts suitable for two adult recipients. This modification of the technique could expand the donor pool for adult recipients.
Adult↗
[Management of severe head-injured patients in the first 24 hours. Resuscitation and initial diagnostic strategy].
Limitation of secondary insults after severe head injury is a permanent concern during the early phase of head trauma management. The objectives are to maintain mean arterial pressure between 80 and 100 mmHg, to avoid hypoxaemia, and to maintain arterial PCO2 near to 35 mmHg. Volume loading can be necessary to improve arterial pressure, and is carried out with isotonic critalloid (NaCl 9/1000) or colloids, with the exclusion of all hypotonic solutions (Ringer lactate or glucose). The use of catecholamines is reserved for patients with unstable haemodynamics despite an adequate volume loading. The rapid sequence induction is recommended for endotracheal intubation and is followed by continuous analgesia-sedation to keep patient-ventilator dysynchrony, but without compromising haemodynamic objectives. Mannitol is used in case of life-threatening intracranial hypertension. Conversely, specific treatment of intracranial hypertension, especially hypocapnia, is not recommended. Initial diagnostic procedures include cerebral tomodensitometry (TDM). However, TDM may be delayed in case of haemorrhage, which requires a rapid treatment. Intrahospital transport for additional explorations risks secondary insults, and thus requires close monitoring to detect and treat in due time all adverse events. This monitoring includes invasive arterial blood pressure assessment, use of continuous capnography and repeated arterial blood gas measurements. The usefulness of transcranial Doppler for initial management of head-trauma patients needs further evaluation.
Brain Injuries↗
Liver transplantation for hepatic arteriovenous malformation with high-output cardiac failure in hereditary hemorrhagic telangiectasia: hemodynamic study.
We describe a case of orthotopic liver transplantation used as a therapeutic method to correct high output cardiac failure related to a liver arteriovenous fistula due to hereditary hemorrhagic telangiectasia. Detailed hemodynamic changes as they occurred during liver transplantation are described.
Adult↗
Enhanced antitumour activity of 6-hydroxymethylacylfulvene in combination with topotecan or paclitaxel in the MV522 lung carcinoma xenograft model.
6-Hydroxymethylacylfulvene (HMAF; MGI 114; Irofulven) is a semisynthetic analogue of the toxin illudin S, which is a product of the Omphalotus mushroom. MGI 114 induces cytotoxicity against a broad range of solid tumours in vivo, including the drug-refractory MV522 human lung cancer xenograft. In this study, the potential application of MGI 114 in the treatment of lung cancer was explored by evaluating the activity of MGI 114 in combination with either topotecan (TPT) or paclitaxel. Groups of eight nude mice bearing MV522 xenografts were treated with MGI 114, TPT or paclitaxel as single agents and with MGI 114 in combination with TPT or paclitaxel. MGI 114 was administered at doses of 2.5 and 5.0 mg/kg intraperitoneally (i.p.) daily on days 1-5, while TPT and paclitaxel were administered at doses of 0.5 or 1.0 mg/kg and 20 mg/kg, respectively, i.p. on days 1-5. In the single-agent studies, MGI 114, TPT and paclitaxel all resulted in decreased final tumour weights compared with vehicle-treated controls. As single agents, TPT, at the 0.5 mg/kg dose level, and paclitaxel, at the 20 mg/kg dose level, produced partial shrinkages (PSs). All combinations of MGI 114, and either TPT or paclitaxel, produced decrements in final tumour weights compared with monotherapy with the same doses of MGI 114, TPT and paclitaxel. Although all animals treated with the combination of MGI 114 and paclitaxel experienced PSs or complete shrinkages (CSs) (or died), analysis of the time to tumour doubling revealed that the combination of MGI 114 and TPT at 2.5 and 0.5 mg/kg, respectively, was synergistic. These results suggest that cytotoxic activity is enhanced when MGI 114 is combined with either TPT or paclitaxel, and clinical trials to further evaluate these combination regimens are warranted.
Animals↗
End-tidal oxygraphy during pre-oxygenation in patients with severe diffuse emphysema.
We hypothetised that the rate of pre-oxygenation could be altered by the increase in lung volume and airflow obstruction observed in emphysema. End-tidal oxygen concentration was monitored, using a paramagnetic oxygen analyser, during 10-min pre-oxygenation (tidal breathing of 100% oxygen) in 10 normal patients and in 10 patients with severe diffuse emphysema documented by computerised tomography. Emphysema was characterised by an important increase in functional residual capacity of the lungs [190 (23)% of predicted values] and a decrease in expiratory flow. The increase in end-tidal oxygen concentration was slower in the emphysema group than in the control group (p = 0.0024). After 3 and 5 min of pre-oxygenation, the end-tidal fractional oxygen concentration was significantly lower in the emphysema group than the control group [mean (SD); value at 3 min: emphysema: 0.83 (0.06) vs. control: 0.91 (0.02), p = 0.0005]. Individual values of end-tidal oxygen concentration measured after 3, 5 and 10 min of pre-oxygenation were negatively correlated with functional residual capacity in the emphysema group, whereas no such correlation was found in the control group. These results suggest that pre-oxygenation should be monitored in patients with diffuse emphysema to ensure that adequate pre-oxygenation is achieved.
Adult↗
Guidelines for perioperative cardiac evaluation from the American College of Cardiology/American Heart Association task force are effective for stratifying cardiac risk before aortic surgery.
PURPOSE: We assessed whether the American College of Cardiology/American Heart Association (ACC/AHA) task force guidelines for perioperative cardiac evaluation could reliably stratify cardiac risk before aortic surgery. METHODS: We retrospectively applied the guidelines to a closed database, set up prospectively. The setting was a referral center in an institutional practice with hospitalized patients. The closed database included 133 patients who had a routine cardiac examination, which comprised an estimation of functional capacity and noninvasive testing, before aortic surgery. This cardiac evaluation led to the proposal of coronarography in 23 patients and to treating an underlying coronary artery disease in 21 patients (including three myocardial revascularizations). One patient died after myocardial revascularization, and two patients died of cardiac causes after aortic surgery. The algorithm of the ACC/AHA guidelines was applied independently by two investigators to each patient's file that was included in the existing database. The main outcome measure was a comparison between cardiac risk stratification with the ACC/AHA guidelines and the results of the routine cardiac evaluation. RESULTS: The ACC/AHA guidelines were successfully applied to all 133 files by the two investigators. After applying the algorithm, 73 patients were stratified as low cardiac risk, and 60 patients were stratified as high risk. The 21 patients who had undergone a preoperative coronary artery disease optimization were stratified as high risk by means of the ACC/AHA guidelines. The patients who died from cardiac causes were stratified as high risk by means of the ACC/AHA guidelines, whereas none of the patients stratified as low risk died during hospitalization. CONCLUSION: The ACC/AHA guidelines were effective in stratifying cardiac risk by using clinical predictors and an estimate of the physical capacity of the patient. Their use may allow a reduction in unnecessary noninvasive testing in patients stratified as being at low risk, while permitting the selection of all patients likely to benefit from preoperative coronary artery disease optimization.
Algorithms↗
The effect of propofol on angiotensin II-induced Ca(2+) mobilization in aortic smooth muscle cells from normotensive and hypertensive rats.
UNLABELLED: We studied the effect of propofol (5.6-560 micromol/L; 1-100 microg/mL) on the mechanisms involved in Ca(2+) mobilization elicited by angiotensin II (AngII) in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We studied the variations in intracellular Ca(2+) ([Ca(2+)](i)) concentrations in cultured aortic vascular smooth muscle cells (VSMCs) isolated from 6-wk-old WKY and SHR rats loaded with the Ca(2+)-sensitive fluorescent dye, Fura-2, using fluorescent imaging microscopy. In the absence of external Ca(2+), AngII (1 micromol/L) induced a transient [Ca(2+)](i) mobilization from internal stores that was larger in SHR than in WKY rats. Ca(2+) influx was assessed after external Ca(2+) (1 mmol/L) reintroduction. Propofol (1-100 microg/mL) added 5 min before the experiments did not alter AngII-induced Ca(2+) release from internal stores in either strain. By contrast, Ca(2+) influx elicited by AngII was significantly decreased by propofol. This effect occurred at a smaller concentration of propofol in the SHR than in the WKY rats. When Ca(2+) stores were depleted by exposure of cells to thapsigargin, an inhibitor of the sarcoendoplasmic reticulum Ca(2+)-ATPase, reintroduction of Ca(2+) to the medium induced a capacitative Ca(2+) influx of similar magnitude than that elicited by AngII. This influx was also significantly decreased by propofol at 100 microg/mL ( WKY: 27 +/- 3% of control values, n = 107; SHR: 16 +/- 3%, n = 47; P < 0.001). In conclusion, propofol decreased AngII-induced Ca(2+) influx through voltage-independent channels, without altering Ca(2+) release from internal stores in aortic VSMCs. The hypertensive rats were found to be more sensitive to the effect of propofol than the normotensive rats. This suggests that the response of VSMCs to AngII may be altered by propofol. IMPLICATIONS: In rat aortic vascular smooth muscle cells, propofol reduced angiotensin II-elicited Ca(2+) entry through capacitative Ca(2+) channels without altering Ca(2+) release from intracellular stores. Spontaneously hypertensive rats were more sensitive to these effects of propofol than normotensive rats. The response of vascular smooth muscle cells to angiotensin II may be altered by propofol.
Anesthetics, Intravenous↗
Intraoperative pacemaker malfunction during a shoulder arthroscopy.
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Aged↗
Enhancement of platelet recovery after myelosuppressive chemotherapy by recombinant human megakaryocyte growth and development factor in patients with advanced cancer.
PURPOSE: To explore the influence of dose and schedule on the ability of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) to abrogate thrombocytopenia after multiple cycles of chemotherapy and to mobilize peripheral-blood progenitor cells (PBPC). PATIENTS AND METHODS: In this open-label study, 68 patients with advanced cancer were randomized to receive PEG-rHuMGDF subcutaneously at different doses and durations before administration of carboplatin 600 mg/m(2), cyclophosphamide 1,200 mg/m(2), and filgrastim 5 microgram/kg/d. PEG-rHuMGDF was not given after the first cycle of chemotherapy but was given after the second and subsequent cycles. Chemotherapy was given every 28 days for up to six cycles. RESULTS: In patients who received the same dose of chemotherapy for at least two cycles, the platelet nadir was significantly higher (47.5 x 10(9)/L v 35.5 x 10(9)/L; P =.003) and duration of grade 3 or 4 thrombocytopenia significantly shorter (0 v 3 days; P =.004) when PEG-rHuMGDF was administered after chemotherapy. There was no evidence of an effect of PEG-rHuMGDF when it was given before chemotherapy. Platelet recovery after the first cycle of chemotherapy was no different for different PEG-rHuMGDF regimens, and there was no difference between patients treated with PEG-rHuMGDF and historical controls treated with identical chemotherapy. There was a modest dose-related increase in progenitor cell levels after administration of PEG-rHuMGDF alone. Peak levels of PBPC occurred later in cycle 2 than in cycle 1 but were not different in magnitude. CONCLUSION: PEG-rHuMGDF abrogated severe thrombocytopenia after dose-intensive chemotherapy. However, it had only a modest effect on progenitor cell levels and did not enhance progenitor cell mobilization after chemotherapy and filgrastim.
Adult↗
Pharmacokinetic analysis of pegylated megakaryocyte growth and development factor in humans.
Phase I studies with pegylated megakaryocyte growth and development factor (PEG-rHuMGDF), a c-Mpl ligand that stimulates megakaryopoiesis, have demonstrated that PEG-rHuMGDF is biologically active alone and causes a dose-related enhancement of platelet recovery when administered after chemotherapy. Here we report the dose-ranging pharmacokinetics of PEG-rHuMGDF. Pre-injection blood samples were drawn daily for pharmacokinetic studies on 43 patients. An ELISA, established using PEG-rHuMGDF as the standard, was able to quantitate Mpl ligand at concentrations > 0.02 ng/mL. Over the dose range 0.03 to 5.0 microg/kg/day, subcutaneous administration produced linear increases in steady-state serum levels. Maximum levels of PEG-rHuMGDF attained after 5.0 microg/kg/day were 5.88 to 10.9 ng/mL. After discontinuation of PEG-rHuMGDF, concentrations of Mpl ligand returned to baseline within 5 days. The pharmacokinetics were best described by a one-compartment model with first-order absorption, an absorption delay, and non linear clearance over the first 48 hours. The mean terminal half-life was 33.3 + 16.7 hours, and the average apparent at steady state was 27.7 + 14.0 mL/h/kg; both were independent of administered dose. The apparent clearance of PEG-rHuMGDF was not predicted by platelet count. Administration of chemotherapy and Filgrastim did not alter the pharmacokinetics of PEG-rHuMGDF.
Antineoplastic Agents↗
The new dioxolane, (-)-2'-deoxy-3'-oxacytidine (BCH-4556, troxacitabine), has activity against pancreatic human tumor xenografts.
There is a great need for new therapeutic agents for patients with advanced pancreatic cancer. The new dioxolane analogue troxacitabine was evaluated in two human pancreatic cancer xenograft models. The models used included the Panc-01 and MiaPaCa pancreatic cancer cell lines. Whereas there is certainly no absolute evidence that either of the in vivo models is predictive for clinical activity, there is at least some evidence that they may be helpful in selecting agents for clinical trials in patients with pancreatic cancer. Troxacitabine was administered i.v. to the animals at doses of 10 and 25 mg/kg on a daily x 5 regimen. Gemcitabine was used as a positive control. The end points for the study included tumor growth inhibition (TGI), final weight, and the number of partial and complete tumor responses in the animals. Troxacitabine was highly active against the Panc-01 model (n = 8), with TGI levels of 88.5% and 84.3% at the 10 and 25 mg/kg doses, respectively. The mean final tumor weights for animals given troxacitabine were also significantly smaller (P < 0.001) compared with vehicle controls. At the 10 mg/kg dose, there were three partial tumor shrinkages and one complete tumor shrinkage, whereas at the 25 mg/kg dose, there were three partial tumor shrinkages. Troxacitabine had less activity against the MiaPaCa model (n = 10) and, by traditional response criteria, would be considered inactive, with TGIs of 4% and 22.7% at the 10 and 25 mg/kg dose level, respectively. Of note is that in comparison with gemcitabine, troxacitabine was more efficacious against Panc-01 and was equally active against MiaPaCa. These in vivo results are encouraging and support the prospect of performing Phase II and perhaps Phase III trials with troxacitabine in patients with advanced pancreatic cancer.
Animals↗
[Criteria for the choice of a curare agent for prolonged administration and resuscitation].
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Anesthesia↗
[What anesthetic for the cirrhotic patient?].
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Anesthesia↗
[Wasting and postoperative infection in cancer patients].
Denutrition decreases immunological responses of non-cancer patients, the healing is altered whereas infectious complications increase. Now during hospitalization, malnutrition prevails in cancer patients. The suppression of the adaptability to fasting which reduces the expenditure of energy at rest, an a normal metabolic response to nutrients' supply with the impossibility to compensate totally the metabolic deficits with the artificial nutrition alone, raise the fear of postoperative disorders, particularly an increase of the infectious risk. The key point is therefore to identify the cachexia's degree owing to a simple, predictive and consensual index. This check-up allows a postoperative complications' prevention by starting up a perioperative refeeding in high-risk subjects: that is to say all severe wasting patients, the people booked for a severe surgical procedure, especially for oesophageal and gastric neoplasms. Actually, we consider that the quality of the results depend more on the making up of the different nutritional solutions dispensed than to strictly providing for cancer patients' wants, which could be harmful in the postoperative period. Supplementation with antioxidant micronutrients or arginine, glutamine, ribonucleic acids and omega-3 fatty acids would allow an immuno- modulation of the renutrition. But complications strictly due to preoperative denutrition are still to be established.
Cachexia↗