Hydrodynamic characteristics of a membrane oxygenator: modeling of pressure-flow characteristics and their influence on apparent viscosity.

The viscosity obtained from pressure-flow characteristics of an oxygenator may help to detect factors that change oxygenator resistance. The objective of this study was to model pressure-flow characteristics of a membrane oxygenator with an integrated arterial filter and to quantify their influence on apparent viscosity of non-Newtonian fluids. One Newtonian fluid (glycerin solution) and two non-Newtonian fluids (whole bovine blood and a human red blood cell suspension) were perfused through an oxygenator and their pressure-flow characteristics examined systematically. Four resistance parameters for the pressure gradient characteristics approximation equation were obtained by the least squares method from the relational expression of pressure-flow characteristics and viscosity. For all three fluids, a non-linear flow to pressure change was observed with a coefficient of determination of almost 1 by exponential approximation. The glycerin solution had a higher pressure gradient (10-70%) than the other fluids; the apparent viscosity of the non-Newtonian fluids was around 35% lower than the static one measured by a torsional oscillation viscometer. Overall, our study demonstrated that the influence on the apparent viscosity of non-Newtonian fluids can be quantified by pressure gradient differences in a membrane oxygenator with an integrated arterial filter.

Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy.

BACKGROUND: The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC). METHODS: Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated. RESULTS: High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced. CONCLUSIONS: Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.

A novel measurement and delivery system for synchronizing oxygen gas flow with blood flow during cardiopulmonary bypass.

Monitoring the blood pump and the oxygen gas flow meter are important maneuvers at the initiation of cardiopulmonary bypass (CPB). We present a novel system, designed to improve safety in the heart-lung machine by linking the control of blood flow and the oxygen gas flow meter. This system uses a mass flow controller to provide and control oxygen flow based on the ventilation-perfusion (V/Q) ratio, using the electronic signal of the blood flow. We tested the system, in vitro and in vivo, and examined the resulting level of blood oxygenation. When extracorporeal circulation was initiated, the oxygen flow was instantly linked to the circulating blood flow, providing an adequate V/Q ratio; the partial pressure of oxygen in the blood was maintained at a normal level. Although we have yet to confirm the safety of this system in clinical trials, the new safety assist device can automatically supply oxygen to the oxygenator at the beginning of CPB.

Peritoneal pharmacokinetics and pharmacodynamic target attainment of meropenem in patients undergoing abdominal surgery.

Although meropenem is commonly used for intra-abdominal infections, its penetration into the abdominal cavity is not well understood. Meropenem (500 mg) was administered intravenously to 8 patients with inflammatory bowel diseases undergoing laparotomy. The drug concentrations were analyzed and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. Meropenem concentrations in peritoneal fluid (PF) and plasma were similar at 1 h after the end of a 0.5-h infusion. The probabilities of target achievement of drug concentrations over the MIC in PF for 40% of the dosing interval with 500 mg every 8 h and 1000 mg every 8 h, were 84% and 90% against Bacteroides spp., 98% and 99% against Escherichia coli , and 76% and 83% against Pseudomonas aeruginosa, respectively. In conclusion, meropenem penetrated PF well, and 500 mg every 8 h or 1000 mg every 8 h would be suitable for the therapy for intraabdominal infections.

Penetration and exposure of cefotiam into the peritoneal fluid of abdominal surgery patients after intravenous administration.

The present study aimed to examine the peritoneal pharmacokinetics and pharmacodynamic exposure of intravenous cefotiam. One gram of cefotiam was administered to eight patients before abdominal surgery. Venous blood and peritoneal fluid (PF) samples were obtained at the end of infusion (0.5 h) and 1, 2, 3, 4, 5, and 6 h afterwards. The drug concentrations in the plasma and PF were determined, analyzed pharmacokinetically, and used for a stochastic simulation with minimum inhibitory concentration (MIC) data. Cefotiam penetrated well into the PF with the area under the drug concentration-time curve ratio of 0.88 +/- 0.18 (mean +/- SD, n = 8). Regarding the pharmacodynamic exposures against Escherichia coli and Klebsiella species, the probabilities of attaining the bacteriostatic target (40% of the time above MIC) in the PF using 0.5 g every 12 h, 1 g every 12 h, and 2 g every 12 h were 88.3-93.6%. However, 1 g every 8 h was needed for 89.7 and 91.6% probabilities of attaining the bactericidal target (70% of the time above MIC). These results should help us to understand better the peritoneal pharmacokinetics of cefotiam while also helping us to choose the appropriate dosage for intra-abdominal infections.

[Pericardioperitoneal fenestration for chronic exudative pericarditis using a subxiphoidal approach; report of a case].

A 77-year-old woman with a previous history of median sternotomy and collagen disease, presented with chief complaints of resting dyspnea as a result of recurrent pericardial effusions or restrictive ventilatory impairment. She experienced significant symptom amelioration after undergoing pericardioperitoneal fenestration. We weighed the positive against the negative of various pericardial effusion drainage methods in this study. This operative procedure is not innovative, but favorable because it can be carried out conveniently and safely, enabling early rehabilitation without appreciable postoperative complications.

Molecular epidemiology of enteritis-causing methicillin-resistant Staphylococcus aureus.

In the early 1990s, severe enteritis caused by methicillin-resistant Staphylococcus aureus (MRSA enteritis) was prevalent in Japan, but the incidence has since decreased. We compared the genotypes and phenotypes of 12 isolates that caused MRSA enteritis (enteritis isolates), detected between 1990 and 1993, with 186 non-enteritis isolates detected between 1998 and 2002. Organisms were investigated using pulsed-field gel electrophoresis (PFGE), coagulase typing and reverse passive latex agglutination to detect production of staphylococcal enterotoxins (SE) and toxic shock syndrome toxin-1 (TSST-1); and polymerase chain reaction (PCR) for detection of the structural genes entA, entB, entC, entD and tst, which encode proteins SE-A, SE-B, SE-C, SE-D and TSST-1, respectively. The 12 enteritis isolates were classified into four types and four subtypes. Only seven of the 186 non-enteritis isolates had PFGE patterns indistinguishable from the enteritis isolates. Eight of the 12 enteritis isolates had entA, entC and tst, and produced high levels of SE-A and TSST-1, but not SE-C. Of the 186 non-enteritis isolates, 157 produced SE-C and TSST-1, but not SE-A. The seven non-enteritis isolates with a PFGE pattern indistinguishable from the enteritis isolates did not produce SE-A, and showed relatively low levels of TSST-1 production. These isolates may have continued to inhabit our ward since the earlier outbreak, but acquired a different phenotype. In conclusion, the disappearance of MRSA enteritis may have resulted from the decreased incidence of enteritis-causing clones and phenotypical changes.

Clinical surveillance of surgical imipenem-resistant Pseudomonas aeruginosa infection in a Japanese hospital.

In order to elucidate any changes in imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in Japan, we examined 511 P. aeruginosa stains isolated from our surgical ward between 1987 and 2001. These isolates were subjected to susceptibility testing against various antipseudomonal agents including imipenem, meropenem, ceftazidime, gentamicin and ciprofloxacin. They were serotyped with the slide agglutination test and genotyped using pulsed-field gel electrophoresis (PFGE). The annual incidences of IRPA infections were particularly high in the early 1990s. Epidemiological investigations revealed that these outbreaks were due to dissemination of hospital-acquired IRPA isolates. Intensive use of imipenem promoted the selection of highly resistant strains. Further study of resistance mechanisms revealed that none of the 110 IRPA strains were metallo-beta-lactamase (MBL) producers. Polymerase chain reaction (PCR) analysis using bla(IMP) specific primers confirmed that no IMP-1 type MBL gene-positive strains were detected from our ward. Susceptibilities of those IRPA strains against other antipseudomonal agents showed relatively low levels, suggesting that imipenem resistance was mainly due to impermeability of the OprD porin. In conclusion, hospital-acquired outbreaks of IRPA were recently reduced by guidelines for, and surveillance of, appropriate use of antimicrobial agents. When the rate of IRPA isolation increases, serotyping should be performed initially and PFGE is required to confirm outbreaks. A computer-assisted genotyping technique is available to perform epidemiological studies of IRPA isolates.

Contractile cardiac grafts using a novel nanofibrous mesh.

Cardiomyoctes are terminally differentiated cells and therefore unable to regenerate after infarction. The use of autologous bioengineered cardiac grafts has been suggested to replace infarcted myocardium and enhance cardiac function. Here we report the development of an in vitro system for engineered myocardium. Cardiac nanofibrous meshes (CNM) were developed by culturing cardiomyocytes from neonatal Lewis rats on electrospun, nanofibrous polycaprolactone (PCL) meshes. The mesh had an ECM-like topography and was suspended across a wire ring that acted as a passive load to contracting cardiomyocytes. The cardiomyocytes started beating after 3 days and were cultured in vitro for 14 days. The cardiomyocytes attached well on the PCL meshes and expressed cardiac-specific proteins such as alpha-myosin heavy chain, connexin43 and cardiac troponin I. The results demonstrate the formation of contractile cardiac grafts in vitro. Using this technique, cardiac grafts can be matured in vitro to obtain sufficient function prior to implantation. It is conjectured that cardiac grafts with clinically relevant dimensions can be obtained by stacking CNMs and inducing vascularization with angiogenic factors.

Endovascular stent-grafting via the aortic arch for distal aortic arch aneurysm: an alternative to endovascular stent-grafting.

OBJECTIVE: We have experienced transaortic stent-grafting for treating distal arch aneurysm or type B dissection. This paper is to mainly report the surgical aspect of these procedures. METHODS: Fifteen patients underwent this surgery, including 12 men and three women ranging from 47 to 83 years. Twelve had aneurysms and three aortic dissection. Concomitant surgery was necessary in seven patients (coronary artery bypass grafting in five, tricuspid annuloplasty in one, and replacement of ascending aorta and/or total arch replacement in three cases). A stent graft (Gianturco Z-stent and Intervascular prosthesis) was loaded in a 30-F sheath catheter. Under circulatory arrest, selective cerebral perfusion was established, and the sheath catheter was inserted through aortotomy into descending aorta and the stent graft was deployed at an appropriate level. The proximal end of graft was sutured to the aorta just distal to the left subclavian artery with inclusion method at the posterior wall. Concomitant surgery was done during cooling or rewarming period. TEE was utilized to visualize every endovascular manipulation to avoid unintended intimal injury or misplacement of graft and to assess the surgical results in the operative theater. RESULTS: Aneurysm was successfully excluded except in one patient who had a proximal endoleak and distal endoleak due to underestimation of aortic diameter. There was one operative mortality caused by cerebral infarction, possibly due to debris from femoral arterial cannulation. In the remaining patients, there was no enlargement of residual aneurysm. The excluded aneurysmal sac gradually regressed and disappeared within 2 years in five patients and the thrombosed false lumen completely shrunk within 1 year in two patients. One patient had paraplegia, possibly because the graft was intentionally advanced deeply to cover the thick and fragile atheromatous layer in order to avoid destruction of the atheroma by an expanded graft. CONCLUSIONS: Endovascular stent graft via the aortic arch is an acceptable treatment for distal arch aneurysms close to or involving left subclavian artery or type B dissections, especially for those cases requiring other cardiac procedures. It can lead to regression and disappearance of aneurysm or dissection in the mid-term follow-up.

Thermal and photochemical solvolysis of (E)- and (Z)-2-phenyl-1-propenyl(phenyl)iodonium tetrafluoroborate: benzenium and primary vinylic cation intermediates.

The thermal and photochemical solvolysis of the two stereoisomeric 2-phenyl-1-propenyl(phenyl)iodonium tetrafluoroborates has been investigated in alcoholic solvents of varying nucleophilicity. The product profiles and rates of product formation in the thermal reaction are all compatible with a mechanism involving cleavage of the vinylic C-I bond assisted by the group in the trans position (methyl or phenyl), always leading to rearranged products. Depending on the nucleophilicity of the solvent, the primarily formed cations may or may not further rearrange to more stable isomers. The less reactive Z compound also yields some unrearranged vinyl ether product in the more nucleophilic solvents via an in-plane S(N)2 mechanism. The mechanism of the photolysis involves direct, unassisted cleavage of the vinylic, and aromatic, C-I bond in an S(N)1 mechanism. This produces a primary vinyl cation, which is partially trapped prior to rearrangement in methanol. The unrearranged vinyl ethers are mainly formed with retention of configuration via a lambda3-iodonium/solvent complex in an S(N)i mechanism. Thermal and photochemical solvolyses of iodonium salts are complementary techniques for the generation of different cation intermediates from the same substrate.

[Serum cytokine levels response to cardiac surgery with cardiopulmonary bypass].

The response of tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra), macrophage colony stimulating factor (MCSF), white blood cell (WBC), platelet (Plt), lactic acid (LAC) to cardiopulmnary bypass (CPB) were studied until 48 hours after aortic declamping in 11 patients who underwent elective CABG (n = 4), mitral valve plasty or replacement with modified maze procedure (n = 5), and both procedures (n = 2). The highest levels of the cytokines IL-6, IL-8, IL-10, and IL-1ra were observed after the removal of the cross clamp. These cytokines just after the aortic declamping are likely to be occurred not only by an interaction of the blood components with the artificial surfaces, but also by ischemia-reperfusion injury upon discontinuation of the aortic clamping. MCSF increased gradually in the late post-CPB phase and reached a peak at 48 hr after aortic declamping. MCSF may play an important role in regulating hematopoiesis on the postoperative days 1 and 2 in patients. In conclusion, the therapy based on the kinetics of these cytokines would be useful for patients undergoing CPB.

Oxidative ring cleavage of cyclic acetals with hypervalent tert-butylperoxy-lambda(3)-iodanes.

[reaction: see text] Exposure of cyclic acetals to 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in the presence of tert-butyl hydroperoxide and potassium carbonate in benzene at room temperature results in oxidative ring cleavage to glycol monoesters via intermediate tert-butylperoxy ortho esters.

Cardiac papillary fibroelastoma on the pulmonary valve: a rare cardiac tumor. okaken@mcai.med.hiroshima-u.ac.jp.

We report the case of a patient with a rare papillary fibroelastoma on the pulmonary valve visualized before surgical intervention. The tumor was an encapsulated, rounded mass. The gelatinous membrane on the surface tore easily, and multiple fronds appeared. This case emphasizes that when there is an encapsulated mass attached to a valve, the initial excision of valve tissue should be as minimal as possible. To avoid unnecessary injury to the valve, it is simple and practical to confirm that the tumor has the appearance of a sea anemone, thus identifying it as a papillary fibroblastoma, a benign tumor.

Kinetics of pro-inflammatory cytokines release in cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: Cytokine induction can occur routinely in cardiac surgery with cardiopulmonary bypass. We have studied the relationships between the kinetics of pro-inflammatory cytokine release and the postoperative organ function. METHODS: Ten adult patients (6 men and 4 women) undergoing elective cardiac surgery with cardiopulmonary bypass, at Hiroshima University Hospital were studied. Patients with acute infection, insulin-dependent diabetes, acute or chronic respiratory failure, renal or hepatic failure, acute cardiogenic shock, and emergency patients were not included. The age of the patient ranged from 44 to 78 years (mean 69 +/- 2.0 years). The type of surgical intervention performed was coronary artery bypass grafting in four patients, mitral valve plasty or replacement with modified maze procedure in another five patients, and both procedures in the other one patient. Plasma cytokine levels until 48 hours after aortic declamping were measured in blood samples. The Respiratory Index and the serum levels of choline esterase and creatinine were also measured. The plasma levels of the pro-inflammatory cytokines (interleukin-6 and interleukin-8) were measured. RESULTS: The highest interleukin-6 levels were significantly correlated with hepatic dysfunction (r = -0.80, p = 0.006) and with renal dysfunction (r = 0.78, p = 0.009). The highest interleukin-8 levels were significantly correlated with respiratory dysfunction (r = 0.86, p = 0.001). CONCLUSION: The highest proinflammatory cytokines levels at 1 hour after aortic declamping were related to damage to postoperative organ functions, involving the lung, kidney and liver.

Pulmonary vein orifice isolation for eliminating paroxysmal atrial fibrillation after ICD implantation.

We treated a patient with dilated cardiomyopathy (DCM) and sustained ventricular tachycardia by an implantable cardioverter defibrillator (ICD). He then suffered from inappropriate ICD shocks triggered by paroxysmal atrial fibrillation (AF). We successfully performed pulmonary vein orifice isolation to eliminate paroxysmal AF. The pulmonary vein orifice isolation was a simple and useful procedure for eliminating paroxysmal AF in patient with decreased left ventricular (LV) function after ICD implantation.