An orthotopic model of ductal adenocarcinoma of the pancreas in severe combined immunodeficient mice representing all steps of the metastatic cascade.

INTRODUCTION: Clinically relevant animal models are needed to evaluate new therapeutic strategies against pancreatic adenocarcinoma, which is almost incurable by established treatment. AIMS: To establish and characterize a metastatic orthotopic transplant model for pancreatic ductal adenocarcinoma in severe combined immunodeficient (SCID) mice. METHODOLOGY: Human pancreatic ductal carcinoma cells, PancTu 1, were implanted either subcutaneously or orthotopically into the pancreas. RESULTS: After 4 weeks, orthotopic transplantation resulted in an extensive local tumor growth of an undifferentiated ductal adenocarcinoma with slight to moderate desmoplastic reaction. The tumor growth and spread resembled the situation in humans, including invasion into adjacent organs causing biliary and stomach obstruction. In addition, tumor metastases to regional lymph nodes of the pancreas, lung, liver, mesentery, and diaphragm, and attached to the kidneys, spleen, and reproductive organs were observed. In contrast, no invasion or metastases could be demonstrated by subcutaneous implanted PancTu I cells. Using immunohistochemical analysis, even single human tumor cells could be detected in blood vessels and metastatic organs, providing evidence that the orthotopic transplant model appropriately reflects the entire process of the metastatic cascade. CONCLUSION: This cancer model in SCID mice appears to be a powerful tool to investigate the identity of metastasis-associated genes and to evaluate preclinically the potency of novel antimetastatic agents in ductal adenocarcinoma of the pancreas.

Chiral separation of six diastereomeric flavanone-7-O-glycosides by capillary electrophoresis and analysis of lemon juice.

The diastereomers of six major flavanone-7-O-glycosides (naringin, prunin, narirutin, hesperidin, neohesperidin and eriocitrin) were completely separated for the first time by chiral capillary electrophoresis (CE) employing various buffers and chiral selectors on the basis of the results achieved in 1998 in our research group by Mellenthin. The following chiral additives to the background electrolyte (BGE) were examined: native cyclodextrins (CDs; alpha-, beta- and gamma-CD), neutral cyclodextrin derivatives (dimethyl-beta-CD, hydroxypropyl-beta-CD, hydroxypropyl-gamma-CD) and charged cyclodextrin derivatives (carboxymethyl-beta-CD, carboxyethyl-beta-CD). The effect of CD type, CD concentration and pH value on chiral recognition will be discussed in the following article. In this work, lemon juice (Citrus limon L.) was also examined by chiral CE. Eriocitrin and hesperidin could be identified as characteristic flavanones and chiral separation of their diastereomers could be achieved according to the developed chiral method by capillary electrophoresis using a 0.2 M borate buffer at pH 10.0 and with 5 mM gamma-CD as chiral selector.

Extracorporeal membrane oxygenation with heparin-coated systems in a 13-month-old infant with acute hypoxic respiratory failure after correction of tetralogy of Fallot.

Hemorrhagic disorders due to systemic heparinization are frequent during extracorporeal lung support (veno-venous extracorporeal membrane oxygenation: vv-ECMO). The development of heparin-coated systems has reduced the need for high-dose heparinization. Whereas the use of these heparin-coated membrane lungs and tubings has been described in former studies in adults, only few reports exist in children. This case report describes the application of a heparin-coated extracorporeal system for long-term vv-ECMO in a 13-month-old infant suffering from acute hypoxic respiratory failure after correction of tetralogy of Fallot. Only moderately elevated levels of activated clotting time (ACT, 120-160 s) and activated partial thromboplastin time (aPTT, 40-60 s) were necessary to avoid thrombotic events in the extracorporeal system. Thoracotomies were performed twice without bleeding complications by discontinuation of the systemic heparinization. We conclude that the use of heparin-coated membrane lungs in infants may improve the safety of extracorporeal lung support and permits surgical intervention without major risk of bleeding.

Extracorporeal lung assist with heparin-coated systems.

Extracorporeal lung assist (ELA) has been recommended for the treatment of ARDS if conventional therapy fails. However, the need for nearly complete anticoagulation is a major risk factor for hemorrhagic complications. We describe our experience with 13 ARDS patients treated with ELA using heparin-coated systems (Carmeda). Maintaining partial thromboplastin time and activated clotting time within or close to the normal range, even major surgery (20 thoracotomies and 2 laparotomies) could be performed without undue bleeding complications related to anticoagulation during extracorporeal support. Eight of the 13 patients survived. The use of heparin-coated systems allows prolonged ELA with nearly physiological coagulation function, permitting major surgical intervention. It enhances the safety margin of extracorporeal gas exchange and may ultimately extend its indications.

Intraoperative vascular assessment for estimation of risk in primary closure of omphalocele and gastroschisis.

Surgical repair of anterior abdominal wall defects is often complicated by a discrepancy between the eviscerated organs and the intra-abdominal space available. Primary closure of the abdominal wall may result in increased intra-abdominal pressure and consecutive circulatory impairment. We report the results of a retrospective and consecutive prospective study evaluating the influence of different witameters on mortality and morbidity in children with gastroschitis and omphalocele. Both studies demonstrated that real-time sonographic investigations, intraoperative Doppler duplex sonography, and colour-coded Doppler sonography provide the oppurtunity to collect objective intraoperative data. Our data indicate that intraoperative vascular assessment facilitates the discrimination between infants who benefit from primary closure and those in whom a staged repair is the treatment of choice.

Increased blood levels of methyl tert-butyl ether but not of ethyl propionate during instillation with contact gallstone dissolution agents in the pig.

We performed experiments in anesthetized piglets with two cholesterol gallstone solvents, methyl tert-butyl ether and ethyl propionate, to determine whether blood levels of either solvent would increase during gallbladder instillation of these solvents under conditions simulating gallstone dissolution. The solvent was oscillated rapidly in and out of the gallbladder with a computer-controlled syringe pump; intraluminal pressure was set below the leakage pressure, and oscillating volume was set below the leakage volume to decrease loss of solvent into the intestine. Blood levels were measured with gas chromatography. Six piglets received methyl tert-butyl ether, and six piglets received ethyl propionate. During 2 hr of instillation with methyl tert-butyl ether, blood levels increased steadily to concentrations averaging 0.3 ml/L blood at 2 hr; during a 6-hr period of instillation, blood levels rose to above 0.4 ml/L blood. Replacement of methyl tert-butyl ether with saline solution in the gallbladder caused blood levels to decline gradually; plasma levels decreased by half in 90 min. In contrast, when ethyl propionate was infused for 2 or 6 hr, blood levels remained below the detection limit, probably because of high first-pass hepatic extraction. We conclude that, under conditions simulating those likely present in patients undergoing contact dissolution of gallbladder stones, the two solvents differ: Ethyl propionate is removed so rapidly from blood that its levels remain undetectable, whereas methyl tert-butyl ether levels in blood (and, presumably, peripheral tissues) increase continuously.(ABSTRACT TRUNCATED AT 250 WORDS)

Remifentanil and propofol for sedation in children and young adolescents undergoing diagnostic flexible bronchoscopy.

Flexible fibreoptic bronchoscopy (FOB) has become a useful diagnostic and therapeutic procedure in children. We investigated 26 patients (3-14 years) for FOB using a new sedation strategy. All patients received oral premedication and inhalation of topical anaesthetic. Sedation for bronchoscopy was achieved with a continuous infusion of remifentanil and intermittent boluses of propofol. Propofol injection was repeated if sedation was inadequate. Sedation could be successfully performed in all children without adverse effects. Endtidal CO2 concentration and arterial oxygen saturation remained stable throughout the study. All children were awake 5+/-1.3 min after stopping remifentanil infusion. Sedation with remifentanil/propofol is a new sedation strategy for diagnostic flexible paediatric bronchoscopy in children with spontaneous ventilation.

[Postoperative analgesia in children after hernioplasty. Wound infiltration with different concentrations of bupivacaine: a pilot study]. / Postoperative Analgesie bei Kindern nach Hernioplastie. Wundinstillation mit verschiedenen Konzentrationen von Bupivacain: eine Pilotstudie.

UNLABELLED: Wound instillation seems to be an easy and preferable way to achieve postoperative analgesia in pediatric hernioplasty. This prospective, randomized and double-blinded pilot-study was initiated to gain preliminary information in order to define the appropriate concentration of local anaesthetic for efficient posthernioplastic analgesia. METHOD: 29 children aged 3.1 to 13.7 (5.25 (3.8-8.2) years were randomly assigned to receive either 0.2 ml/kg bupivacaine 0.125% (n = 10), bupivacaine 0.25% (n = 10) or bupivacaine 0.5% (n = 9). The local anesthetic (LA) was instillated intraoperatively before wound closure above the external oblique muscle and below Scarpa's fascia. After entering the post-anesthetic care unit (PACU) pain was assessed by a trained nurse using the linear analogue pain scale (LAPS) in intervals of 15 min. Patients were observed in the PACU for 30-60 min. Pain was further evaluated for 5.5(3-6) h in the ward every hour. In day-only patients the parents were contacted 24 h postoperatively to obtain additional information. RESULTS: From the beginning of the observation period the 0.5% group tended to have less pain than the others in the PACU. The 0.125% and 0.25% group required earlier supplementary analgetics. In addition, the 0.5% group needed once (1/9) supplementary analgesics; the 0.25% group five times (5/10) and the 0.125% group six times (6/10). None of these results is statistically significant, though they appear to be clinically relevant. DISCUSSION: Wound instillation with 0.2 ml of bupivacaine 0.5% seems to be easy to perform, safe and efficient in controlling posthernioplastic pain. Because of the small numbers of patients included however, no statistically significant differences were observed between the groups. Neither in the LAPS on arrival and observation at the PACU nor in the need for supplementary analgesics. Despite lacking significance the clinical impression suggests a difference to be validated by larger studies. Our data implies that wound instillation with 0.2 ml/kg bupivacaine 0.5% should be regarded for routine usage.

Cytokine pattern in patients with infections after liver transplantation.

Severe infections are the most frequent cause of death after liver transplantation. Determination of new parameters may increase the knowledge of pathophysiological mechanisms of infection. For this purpose, 81 patients with 85 liver transplants were monitored for various new parameters on a daily basis. Patients with severe infections (n = 10) were compared with patients with mild or asymptomatic cholangitis (n = 11) and with patients with an uneventful postoperative course (n = 37). One-year patient survival was 88.9%; in five patients, death was related to serious infections. Mean neopterin, soluble tumor necrosis factor-RII (sTNF-RII), and hyaluronic acid levels were significantly elevated in patients with serious infections compared with the other two groups (P < or = 0.01). A further increase in sTNF-RII and neopterin levels was observed in patients with lethal infections (P < or = 0.01 versus surviving patients with serious infection). An increase in neopterin levels was observed prior to severe infection, and in six of ten patients, this increase occurred as early as during the reperfusion period. Soluble TNF-RII and hyaluronic acid levels also increased significantly prior to severe infection. Interleukin (IL)-6, soluble intercellular adhesion molecule-1 (sICAM-1), and sIL-2R increased in patients with serious infection and cholangitis to a similar extent. As part of an overwhelming immune response, a significant increase in IL-6, sIL-2R, and also IL-1 beta levels occurred during the late phase of lethal infection (P < or = 0.01 versus surviving patients with serious infection). Routine monitoring of these parameters may improve current diagnostic tools and possibly lead to earlier detection of patients at risk after liver transplantation.