[Risk and control of nosocomial infection during resuscitation: statement of the Sfar/SRLF].
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Critical Care↗
Biomedical subjects
Y Malledant
Publications and source records attributed to Y Malledant.
Modulation of airway remodeling-associated mediators by the antifibrotic compound, pirfenidone, and the matrix metalloproteinase inhibitor, batimastat, during acute lung injury in mice.
Matrix metalloproteinases (MMPs) are potent to degrade basement membrane collagen associated with acute lung injury in inflammatory processes. We have investigated effects of pirfenidone, antifibrotic agent, and batimastat, inhibitor of MMPs, on gelatinase activities, on release of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), as well as on recruitment of inflammatory cells in bronchoalveolar lavage (BAL) fluid after aerosol administration of lipopolysaccharide (LPS) in mice. Pretreatment with pirfenidone reduced neutrophil recruitment, TNF-alpha and TGF-beta levels, and MMP-9 secretion. In contrast, pretreatment with batimastat (30 or 60 mg/kg, i.p.) only reduced TNF-alpha and TGF-beta levels. Batimastat did not reduce MMP secretion in BAL fluid but inhibited MMP-9 activity. The increase in tissue inhibitor of matrix metalloproteinase (TIMP)-1 induced by LPS was not modified by the two drugs. These findings demonstrate that the two drugs can inhibit the in vivo increase in MMP induced by LPS, batimastat with a direct inhibitor effect on MMP activity and pirfenidone as a consequence of its antiinflammatory effect.
Acute Disease↗
Surgical complications and treatment during resection for malignancy of the high bile duct.
From January 1968 to January 1997 a series of 50 of 109 patients had undergone resection for high bile duct cancer in our institution in Rennes, France. The overall operative mortality was 12%, but there were no deaths among those who had only tumor resection or those with hepatectomy with vascular reconstruction. The early complications were biliary fistula (four cases) and subphrenic abscess (three cases), of which two of the biliary fistulas resulted in mortality. There were three gastrointestinal hemorrhages; one was due to gastritis related to hepatorenal insufficiency and was fatal. Two other deaths were due to respiratory failure and ascites associated with hepatic insufficiency. In one patient after liver transplantation with cluster resection, a biliary leak and ileocolic fistula were the cause of postoperative mortality. Another patient suffered a ruptured mycotic aneurysm after pretransplant transtumoral intubation, which emphasizes the risk of infection in an immunosuppressed patient. The main late complication was cholangitis (8 cases). This complication is most often a symptom of recurrence (four cases). Some are due to benign causes (intrahepatic lithiasis, intrahepatic foreign body granuloma). Surgical exploration is mandatory to exclude benign complications, which can then be treated palliatively. Four patients presented with recurrence but without cholangitis. In conclusion, the causes of complications after resection of high bile duct cancer should be carefully assessed to choose the correct treatment. Late cholangitis is a symptom of recurrence, but it should be explored and managed precisely.
Adult↗
Post-traumatic course complicated by cutaneous infection with Absidia corymbifera.
Cutaneous mucormycosis is a rare but serious infection in trauma patients. Reported here is the case of a young patient with cutaneous mucormycosis due to Absidia corymbifera probably caused by a soil-contaminated wound. Despite daily surgical debridement and amphotericin B therapy, cure could be achieved only by amputation of the lower limb.
Absidia↗
Survival, proliferation, and functions of porcine hepatocytes encapsulated in coated alginate beads: a step toward a reliable bioartificial liver.
Orthotopic liver transplantation is the most effective treatment for fulminant hepatic failure. As an alternative treatment, an efficient extracorporeal bioartificial liver should contain a large yield of functional hepatocytes with an immunoprotective barrier, for providing temporary adequate metabolic support to allow spontaneous liver regeneration or for acting as a bridge toward transplantation. Survival, proliferation, and functions of porcine hepatocytes were evaluated in primary cultures and after embedding in alginate beads, which were subsequently coated with a membrane made by a transacylation reaction between propylene glycol alginate and human serum albumin. Disruption of total pig livers by collagenase perfusion/recirculation allowed the obtention of up to 10(11) hepatocytes with a viability greater than 95%. Hepatocytes in conventional cultures or embedded in coated alginate beads survived for about 10 days, secreted proteins, particularly albumin, and maintained several phase I and II enzymatic activities, namely ethoxyresorufin-O-deethylase, oxidation of nifedipine to pyridine, phenacetin deethylation to paracetamol, glucuroconjugation of paracetamol, and N-acetylation of procainamide. Typical features of mitosis and [3H]thymidine incorporation indicated that porcine hepatocytes proliferated in both conventional cultures and alginate beads. The efficacy of the membrane surrounding alginate beads for protecting cells from immunoglobulins was tested by embedding HLA-typed human lymphocytes, which were subsequently incubated with specific anti-HLA immunoglobulin G and complement. These data show that large yields of porcine hepatocytes that are embedded in coated alginate beads remain functional and are isolated from large molecular weight molecules, such as immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver, containing xenogeneic hepatocytes, to treat acute liver disease in humans.
Acetaminophen↗
Leiden factor V mutation in four patients with small bowel infarctions.
The Leiden factor V mutation is observed in 20% of unexplained lower limb venous thromboses and involves substitution of the arginine residue at position 506 by glutamine (R506Q). It is known to decrease the anticoagulant activity of activated protein C. This case report describes 4 cases of small bowel infarction (SBI) associated with the presence of this mutation. Two cases of arterial and 2 cases of venous SBI were observed. Extensive assessment excluded the usual causes of SBI and plasma hypercoagulation syndrome (antithrombin III, protein C, and protein S deficiency and myeloproliferative syndrome). An abnormal resistance to activated protein C was observed. Molecular analysis consisting of polymerase chain reaction amplification and digestion with MnlI showed that 2 patients were heterozygous and 2 were homozygous for the R506Q mutation. Despite familial history of thrombosis in only 1 patient, first- and second-degree relatives of 2 patients also had the presence of the mutation. Examination for the presence of abnormal resistance to activated protein C should be part of the etiological assessment of SBI. Its presence may warrant consideration of long-term anticoagulant therapy, especially for patients with shortened small bowel who are treated by home parenteral nutrition with deep venous access.
Adult↗
Use of a pneumatic tourniquet induces changes in central temperature.
Twenty-six patients requiring orthopaedic surgery were anaesthetized and oesophageal and rectal temperature were monitored continuously. Twenty patients requiring a pneumatic tourniquet were allocated prospectively to one of two groups: passive group (Pg) with reflective insulation on all available skin surface (n = 10) and forced group (Fg), with active warming by a forced air system (n = 10). Six patients without a tourniquet were used as a reference group (Rg). The pneumatic tourniquet time was similar in the tourniquet groups. During tourniquet inflation, oesophageal temperature increased with time. The difference was significant compared with the reference group at approximately 20 min. At about 30 min, oesophageal temperature in group Fg was significantly higher than that in group Pg. After tourniquet deflation, temperature decreased transiently. Changes in rectal temperature were similar but delayed significantly. A mechanism to explain the increase in core temperature during pneumatic tourniquet use remains unclear. A redistribution mechanism by cooling of the blood in a cold and vasodilated limb could explain the decrease of temperature after tourniquet deflation.
Adolescent↗
Labeled granulocyte scanning for the diagnosis of infected necrosis in acute pancreatitis: what kind of labeling should be used?
Clinical and laboratory data or imaging results cannot provide a positive diagnosis of septic complications of pancreatic and peripancreatic necrosis in patients with acute pancreatitis. Confirmation can be obtained only after percutaneous computed tomography (CT)-guided aspiration of the necrotic tissues or fluid collection; although the important role of 99Tc(m)-HMPAO-labeled granulocyte scintigraphy has been recently emphasized. The aim of this study was to determine the sensitivity and specificity of 99m-technetium-hexamethylpropyleneamine oxime (99Tc(m)-HMPAO)- or 111In-oxine-labeled granulocyte scintigraphy for the diagnosis of infection in pancreatic or peripancreatic necrosis to define the ideal label for diagnosis. Thirty-six scintigraphic examinations were performed in 34 consecutive patients (mean age, 58 +/- 2 years) 20 +/- 2 days after the onset of acute pancreatitis (Balthazar classes A-C, n = 7; classes D and E, n = 29). The scintigraphic study included scintigraphic tomography and static acquisition 1 and 3 h, respectively, after reinjection of the autologous 99Tc(m)-labeled granulocytes and static images 3-4 and 24 h after the simultaneous reinjection of 111In-oxine-labeled autologous granulocytes. The diagnosis of infected pancreatic or peripancreatic necrosis was confirmed with percutaneous CT-guided aspiration (14 positive aspirates among 20 performed) and sterile necrosis after negative aspiration (6 negative aspirates) or after a 6 +/- 1-month follow-up free of clinical or biological signs of ongoing sepsis. The sensitivity and specificity were 86 and 73%, respectively, for scintigraphic tomography, 100 and 55% for 3-h 111In images, 93 and 68% for 3-4-h 111In images, and 100 and 64% for 24-h 111In images. The fall in splenic activity between the 3-4 and the 24-h 111In images was 26 +/- 3% in patients with septic pancreatic and peripancreatic necrosis (n = 14) and 16 +/- 3% in those with sterile necrosis (n = 22) (p < 0.01). Labeled granulocyte scintigraphy was thus shown to be an effective tool for the diagnosis of infection in pancreatic and/or peripancreatic necrosis due to acute pancreatitis, especially when the scintiscans are performed early after injection of 99Tc(m) or when the fall in splenic activity over the 24 h following reinjection of 111In is measured in particularly difficult cases. These promising preliminary results should be confirmed by a prospective study.
Acute Disease↗
Retrosternal bypass operation for unresectable squamous cell cancer of the esophagus.
BACKGROUND: A palliative bypass operation may be beneficial when severe dysphagia or tracheoesophageal fistula occurs after radiochemotherapy for unresectable tumor of the esophagus. METHODS: Thirty-two patients with an unresectable tumor of the esophagus underwent a palliative retrosternal gastric (29) or colonic (3) bypass operation with ligature of the lower esophagus (3) or drainage (27). Tracheoesophageal fistula was present at operation in 20 (62.5%), including 8 after radiochemotherapy. RESULTS: The overall operative mortality rate was 34.4%: 45% with tracheoesophageal fistula and 16.6% without (p < 0.01). Median intensive care and hospitalization times were 5 and 19 days, respectively. Median postoperative survival was 6 months (range, 53 to 492 days). Complications in 21 survivors were lung infections (seven), cervical fistulas (eight), and failure of the esophageal suture (two); 19 patients resumed oral nutrition, and quality of life was excellent in 6. All eight cervical fistulas regressed favorably. Postoperative radiotherapy or chemotherapy did not improve survival. CONCLUSIONS: Despite the high operative mortality rate, bypass operation can provide good palliation and allow subsequent radiochemotherapy in selected patients with an unresectable tumor of the esophagus.
Adult↗
[Abdominal syndromes and analgesia].
Despite physiological advances and recent progress in pain relief, early analgesia for patients with acute abdominal pain is not a conventional endpoint. In clinical practice, priority is often given to diagnosis and management decisions. There are few controlled trials to settle the issue and opinions are still divided. recent studies suggest than early and effective analgesia in acute abdomen does not interfere with diagnosis, and even facilitates initial examination. Various modes of analgesia can be considered.
Abdominal Pain↗
[Evaluation of the cost of autologous erythrocyte concentrates in a hospital].
This study evaluated the cost of autologous and homologous blood products. The cost effectiveness of the transfusion therapy was not evaluated. To compare the different products, the cost of one gram of transfused haemoglobin was calculated. Acute normovolaemic haemodilution is the most economical technique. Intraoperative autologous transfusion without washing is the most expensive. All blood products from the autologous techniques, except the latter, were less expensive than homologous red cells.
Blood Transfusion, Autologous↗
Human hepatocytes express trifluoroacetylated neoantigens after in vitro exposure to halothane.
Biotransformation of anaesthetic halothane by cytochrome P450-dependent monooxygenases resulted in the production of reactive intermediate trifluoroacetyl (TFA) halide, capable of covalently binding to hepatocyte proteins. TFA-modified liver proteins can act as antigens and are implicated in the pathogenesis of halothane hepatitis in humans. The aim of this study was to investigate the formation of TFA-neoantigens in halothane-treated primary cultures of adult human hepatocytes and to evaluate the usefulness of this in vitro model for studying immune-mediated halothane hepatotoxicity. Cultured human hepatocytes were incubated with halothane under constant temperature, atmosphere and anaesthetic concentration conditions. The results obtained show that halothane-treated hepatocytes isolated from seven different donors produced TFA-antigens as detected by immunocytochemical and western immunoblot analysis using rabbit anti-TFA antiserum. TFA-adducts were localized mainly in the endoplasmic reticulum and in small amounts on the plasma membrane of parenchymal cells. By immunoblotting, several neoantigens, with molecular masses from 42 to 100 kDa, were detected in halothane-exposed hepatocytes. These observations are consistent with the formation of TFA-adducts through metabolism of the anaesthetic and suggest that primary cultures of human hepatocytes represent a suitable in vitro model to study the pathogenesis of immune-mediated halothane hepatotoxicity.
Antibody Specificity↗
[Bilateral phrenic nerve paralysis after heart surgery].
A bilateral phrenic nerve paralysis after open heart surgery with cold cardioplegia in a 78-year-old patient is reported. This injury is observed after aortic valve replacement without use of an ice slush around the pericardium and no surgical or other direct nerve trauma. The diagnosis of clinical and radiologic abnormalities suggestive of phrenic dysfunction is assisted by portable sonography and measurement of the diaphragmatic compound muscle action potential after cervical transcutaneous phrenic nerve stimulation. This bilateral phrenic nerve paralysis required prolonged mechanical ventilation for 68 days with incomplete regression of the neuropathy five months after surgery.
Aged↗
Halothane-induced cytotoxicity to rat centrilobular hepatocytes in primary culture is not increased under low oxygen concentration.
BACKGROUND: Halothane can be metabolized by both oxidative and reductive pathways in the liver. This anesthetic can induce direct liver injury preferentially localized in centrilobular areas, probably in relation with lower oxygen tension. The reductive pathway has been related to liver damage; however, a correlation between lower oxygen concentration in centrilobular areas, the extent of reductive metabolism of halothane, and the degree of liver injury has not yet been demonstrated. This study was designed to better evaluate the toxicity of the reduced metabolites by using centrilobular and periportal rat hepatocyte subpopulations. METHODS: Adult rat hepatocytes, either as whole cell preparations or after separation in centrilobular and periportal cell subpopulations, were placed in primary culture and exposed to either 2% or 4% halothane under various oxygen concentrations. The enriched centrilobular hepatocyte subpopulations isolated by the digitonin-collagenase method were characterized by immunolocalization of glutamine synthetase. Three oxygen concentrations were tested: 5%, 20%, and 95%, and the main parameters measured were cell viability and fluoride ion formation. RESULTS: Viability of centrilobular hepatocytes was similar under 5% and 20% O2, but the unpurified hepatocyte population was more susceptible to 5% O2 (P < 0.01). Significantly higher cytochrome P-450 content was found in whole hepatocyte populations under 5% versus 20% oxygen, indicating that centrilobular hepatocytes that contained higher cytochrome P-450 monooxygenase activities were less sensitive to low oxygen concentrations. Halothane toxicity to centrilobular hepatocytes was enhanced under 95% versus 20% O2 (P < 0.05). By contrast, no significant difference was observed when the cells were maintained under 5% O2, although fluoride ions, indicative of reductive metabolism of halothane, were found in much higher amounts in the culture medium. Moreover, under 20% O2, halothane toxicity was significantly greater in centrilobular versus unpurified hepatocytes (P < 0.05). CONCLUSIONS: Isolated centrilobular hepatocytes appear to be more sensitive to halothane than their periportal counterparts in vitro. However, the authors' results support the conclusion that increased reductive metabolism of halothane induced by decreasing oxygen concentration is not a critical parameter for the occurrence of liver damage in these cells.
Animals↗
Steady-state pharmacokinetics of dopamine in adult patients.
OBJECTIVE: To study the pharmacokinetics of dopamine in hemodynamically stable adult patients. DESIGN: Prospective clinical study. SETTING: University hospital intensive care unit. PATIENTS: Fourteen patients (aged 43 to 73 yrs) recovering from esophageal surgery. INTERVENTION: Dopamine was infused and blood samples were collected. MEASUREMENTS AND MAIN RESULTS: Plasma dopamine concentrations were measured at steady state and subsequently at the end of the dopamine infusion using high-performance liquid chromatography. Clearances, volume of distribution, mean residence times, half-lives, and elimination and distribution rate constants were derived. The clearances were independent of the infusion rate at 1, 3, and 6 micrograms/kg/min, and ranged between 0.050 and 0.056 L/min/kg. A two-compartment open model was fitted to the postinfusion plasma concentration data obtained at 3 and 6 micrograms/kg/min. On average, the steady-state volume of distribution and the apparent terminal elimination half-life increased with the dose: 0.78 to 1.58 L/kg, respectively, and 22.1 to 37.9 mins, respectively, for the rates of 3 and 6 micrograms/kg/min. The rate constant associated with the uptake of dopamine into the peripheral compartment (K12) was on average four to five times higher than the rate constant associated with the reverse process (K21). CONCLUSIONS: The redistribution of dopamine into the central compartment could be the main factor involved in the apparent terminal elimination of dopamine from plasma. Due to the relative rates of distribution and elimination, the attainment of a steady-state plasma concentration of dopamine should only depend on the terminal half-life. These results, which remain to be validated in a greater number of patients, indicate that the attainment of 90% of the plateau (i.e., in 3.3 half-lives) would require 70 to 125 mins, depending on the infusion rate.
Adult↗
Stereoselective biliary elimination of disopyramide and mono-N-desisopropyldisopyramide in humans.
The results of a previous pharmacokinetic study of disopyramide (DP) enantiomers in humans suggested that DP and/or mono-N-desisopropyldisopyramide (MND) may show stereoselective extrarenal elimination. Thus, the present study investigates the biliary elimination of DP and MND enantiomers in three patients who had undergone cholecystectomy for cholelithiasis. DP and MND enantiomers displayed biliary elimination. In both subjects, this elimination pathway showed the same characteristics: (1) biliary elimination of DP and MND was stereoselective, (2) the stereoselectivity was opposite to that observed for the metabolic and renal elimination pathways, i.e., the elimination of the (-)-(R)-enantiomer was higher than that of the (+)-(S)-enantiomer, and (3) biliary elimination of MND was higher than that of DP, for both enantiomers. Estimates of the relative contribution of the biliary clearance in the total clearance of DP and MND indicated that this elimination pathway was secondary, especially for DP. The biliary clearance (expressed as % of total clearance) was 1.9 to 4.0% for (-)-(R)-DP, 1.2 to 1.7% for (+)-(S)-DP, 7.8 to 22.9% for (-)-(R)-MND, and 5.2 to 10.5% for (+)-(S)-MND.
Bile↗
[Combination of propofol and alfentanil for corneal surgery in a patient with Duchenne de Boulogne disease].
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Adolescent↗