Sevoflurane-enriched blood cardioplegia: the intramyocardial delivery of a volatile anesthetic.

Myocardial ischemia/reperfusion injury is a major problem in cardiac surgery, characterized by an enhanced inflammatory response postoperatively. Sevoflurane has anti-inflammatory effects and may attenuate this injury. This study describes a novel approach to using sevoflurane as a local anti-inflammatory drug and not as an anesthetic. Therefore, a pediatric oxygenator with a sevoflurane vaporizer was integrated into the blood cardioplegia system of an adult bypass system. In addition, a gas blender was implemented to regulate pO2 and pCO2 concentrations in the cardioplegia. This proof-of-principle study was tested in vivo and shows that it is feasible to deliver sevoflurane locally while regulating O2 and CO2 concentrations. Moreover, this set-up enables one to use only the specific cardioprotective features of sevoflurane. Inflammatory responses were attenuated, both locally (i.e. the heart) as well as systemically through intramyocardial delivery of sevoflurane.

Comparison of closing-wedge and opening-wedge high tibial osteotomy for medial compartment osteoarthritis of the knee: a randomized controlled trial with a six-year follow-up.

BACKGROUND: Varus deformity increases the risk of progression of medial compartment knee osteoarthritis. The aim of this study was to investigate the clinical and radiographic mid-term results of closing-wedge and opening-wedge high tibial osteotomy when used to treat this condition. METHODS: From January 2001 to April 2004, ninety-two patients were randomized to receive either a closing-wedge or an opening-wedge high tibial osteotomy. The clinical outcome and radiographic results were examined preoperatively; at one year; and, for the present study, at six years postoperatively. The outcomes that we reviewed included maintenance of the achieved correction, progression of osteoarthritis (based on the Kellgren and Lawrence classification), severity of pain (as assessed on a visual analog scale [VAS]), knee function (as measured with the Hospital for Special Surgery [HSS] score and Knee injury and Osteoarthritis Outcome Score [KOOS]), walking distance, complications, and survival with conversion to a total knee arthroplasty as the end point. The results were analyzed on the basis of the intention-to-treat principle. RESULTS: Six years postoperatively, the mean hip-knee-ankle (HKA) angle (and standard deviation) was 3.2° ± 4.1° of valgus after a closing-wedge high tibial osteotomy and 1.3° ± 5.0° of valgus after an opening-wedge high tibial osteotomy (p = 0.343). In both groups, the six-year postoperative HKA angles did not differ from the respective one-year postoperative angles. No difference in the severity of pain or in knee function was found between the two groups. Four complications (9%) occurred in the closing-wedge group and seventeen (38%), in the opening-wedge group. Ten (22%) of the patients in the closing-wedge group and three (8%) in the opening-wedge group needed conversion to a total knee arthroplasty within the six-year period (p = 0.05). The difference in the percentage of cases with conversion to total knee arthroplasty was 14% (95% confidence interval [CI] = 21.7 to 0.2). CONCLUSIONS: In the group of patients without conversion to a total knee arthroplasty, there was no difference between the high tibial closing-wedge and opening-wedge osteotomies in terms of clinical outcomes or radiographic alignment at six years postoperatively. Opening-wedge osteotomy was associated with more complications, but closing-wedge osteotomy was associated with more early conversions to total knee arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Cardiospecific sevoflurane treatment quenches inflammation but does not attenuate myocardial cell damage markers: a proof-of-concept study in patients undergoing mitral valve repair.

BACKGROUND: Inflammation is considered a key mediator of complications after cardiac surgery. Sevoflurane has been shown to quench inflammation and to provide cardioprotection in preclinical studies. Clinical studies using sevoflurane confirm this effect on inflammation but do not consistently show clinical benefits. This paradox may indicate that the contribution of inflammation to postoperative sequalae is less than commonly thought or that systemic doses are too low in their local concentration. To test the latter, we evaluated the effects of intramyocardial sevoflurane delivery. METHODS: Selective myocardial sevoflurane delivery was performed during aortic cross-clamping in patients undergoing valve surgery (n=11). Results were compared with a control group not receiving sevoflurane (n=10). A reference group (n=5) was added to evaluate the effects of systemic sevoflurane delivery. Paired arterial and myocardial venous blood samples were collected at various time points post-reperfusion. Inflammatory mediators and myocardial cell damage were studied. RESULTS: Intramyocardial delivery was superior to systemic delivery in attenuation of interleukin-6 and interleukin-8 (-44% and -25%, respectively; both P=0.001). Myocardial and systemic sevoflurane delivery effectively suppressed surgery-related inflammatory responses including postoperative C-reactive protein levels when compared with controls [63 (47-99) (P=0.01) and 58 (56-81) (P=0.04) compared with 107 (79-144) mg litre(-1)]. Sevoflurane treatment did not reduce postoperative troponin T, creatine kinase, and creatine kinase-MB values. CONCLUSIONS: This proof-of-concept study suggests that intramyocardial delivery compared with the systemic delivery of sevoflurane more strongly attenuates the systemic inflammatory response after cardiopulmonary bypass without reducing postoperative markers of myocardial cell damage. CLINICAL TRIAL REGISTRATION: Nederlands Trial Register NTR2089.

The effect of suprapubic catheterization versus transurethral catheterization after abdominal surgery on urinary tract infection: a randomized controlled trial.

BACKGROUND/AIM: Transurethral catheterization is generally associated with a higher incidence of urinary tract infections than suprapubic catheterization; however, suprapubic catheterization is associated with other disadvantages such as higher costs and a more difficult technique, and at the moment there is no consensus about the use of both catheter systems. Therefore, a prospective randomized study was performed to investigate the effects of suprapubic catheterization and transurethral catheterization in patients undergoing surgery on the incidence of urinary tract infections and patient satisfaction. METHODS: Patients who underwent an elective laparotomy were randomized and received a suprapubic or transurethral catheter. The primary end point was urinary tract infection. Other parameters of urinary tract infection, as well as duration of catheterization, hospital stay, and number of recatheterizations and of relaparotomies were monitored. Treatment 'per protocol' was also analyzed after exclusion of patients receiving another catheter than randomized for. Patients were asked for their satisfaction with the catheters and complaints during and after catheterization. RESULTS: 165 patients were eligible, of whom 19 patients had to be excluded. 75 patients were allocated to receive the suprapubic catheter and 71 the transurethral catheter. There was no difference in the incidence of a urinary tract infection between the suprapubic group (n = 9/75; 12%) and the transurethral group (n = 8/71; 11%). Most patients (6/9) who developed a urinary tract infection in the suprapubic group, however, underwent recatheterization because of postoperative complications/sepsis and relaparotomy. The incidence of urinary tract infections in patients who received a suprapubic catheter and not a transurethral catheter was 3/59 (5%). The patients did not differ with respect to satisfaction and complaints. Being a men, recatheterization and duration of catheterization are risk factors. CONCLUSIONS: The incidence of a urinary tract infection between a suprapubic catheter and a transurethral catheter in patients undergoing major surgery was not different. A potential advantage of the suprapubic catheter (reduction of urinary tract infections) is probably partly negated, because transurethral catheters were used if recatheterization was indicated during the postoperative stay or due to complications.

Urine interleukin-8 is a marker for urinary tract infection in postoperative patients.

BACKGROUND: Urine of patients with urinary tract infection (UTI) contains high levels of interleukin (IL)-6 and IL-8. However, knowledge of the kinetics of their release in urine is limited. We therefore compared the appearance of IL-6 and IL-8 in urine after uncomplicated surgery and surgery complicated by UTI. PATIENTS AND METHODS: 165 patients undergoing abdominal surgery who received a urinary catheter were studied. Urine IL-6 and IL-8 were prospectively measured in patients who did (n = 10) or did not (n = 20) develop UTI. Statistical analysis was done by one-way ANOVA and the Mann-Whitney test. RESULTS: Although urine IL-6 increased in the 2 to 4 days preceding the bacteriological documentation of UTI, a similar increase was observed in patients who did not develop UTI. Urine IL-8 was elevated on the day UTI was diagnosed, while remaining low in controls. CONCLUSION: In this patient group with postoperative UTI, urine IL-8 was a better marker for the early host response than urine IL-6.

Involvement of mitochondria in the assimilatory metabolism of anaerobic Saccharomyces cerevisiae cultures.

The possible physiological role of mitochondria in anaerobically grown Saccharomyces cerevisiae was investigated via enzyme localization and inhibitor studies. Almost all of the activity of citrate synthase (EC 4.1.3.7) was recovered in the mitochondrial fraction after differential centrifugation of spheroplast lysates. The enzyme exhibited a high degree of latency which was demonstrated by sonication of the mitochondrial fractions. Since citrate synthase is an important enzyme in anabolic reactions, a consequence of this localization is the requirement for transport of metabolites across the mitochondrial membranes. Such transport is likely to require energy which, as a result of anaerobiosis, cannot be supplied by respiration. It was therefore investigated whether ATP translocation into the mitochondria by an ADP/ATP translocase might be involved in anaerobic mitochondrial energy metabolism. It was shown that addition of the ADP/ATP translocase inhibitor bongkrekic acid to anaerobic cultures indeed inhibited growth, although only partially. It is concluded that mitochondria of S. cerevisiae fulfil a vital role in anaerobic sugar metabolism.

Technical evaluation of three second generation CA 125 assays.

The analytical performance of five CA 125 assays was studied using samples from apparently healthy women (n = 28) and from a group of patients with gynaecological malignancies (n = 260). Investigations were carried out on two homologous sandwich assays using the monoclonal antibody OC 125 (LIA-mat I and IRMA-mat I) and three heterologous assays using the monoclonal antibodies OC 125 and M11, both directed against the carcinoantigen CA 125 (LIA-mat CA 125 II, IRMA-mat CA 125 II, Centocor CA 125 II). The precision of the LIA-mat CA 125 II was better than that of the previously used LIA-mat I, the intra-assay coefficients of variation being 6.5% and 11.6% respectively. Using the new generation CA 125 II assays, only 0.5% of the duplicate measurements had to be rejected. The inter-assay coefficient of variation of the automated LIA-mat CA 125 II ranged from 7.1% to 11.2% while the IRMA-mat CA 125 II inter-assay CV ranged from 11.6% to 13.9%. Serum EDTA or heparin plasma did not give significantly different results. A carry-over of 0.02% was observed using the LIA-mat S 300 system. A high dose hook effect may be observed with concentrations over 20000 kU/l. All assays showed excellent linearity, and there was a good correlation between the assays.

Production and localization of beta-fructosidase in asynchronous and synchronous chemostat cultures of yeasts.

In synchronized continuous cultures of Saccharomyces cerevisiae CBS 8066, the production of the extracellular invertase (EC 3.2.1.26) showed a cyclic behavior that coincided with the budding cycle. The invertase activity increased during bud development and ceased at bud maturation and cell scission. The cyclic changes in invertase production resulted in cyclic changes in amounts of invertase localized in the cell wall. However, the amount of enzyme invertase present in the culture liquid remained constant throughout the budding cycle. Also, in asynchronous continuous cultures of S. cerevisiae, the production and localization of invertase showed significant fluctuation. The overall invertase production in an asynchronous culture was two to three times higher than in synchronous cultures. This could be due to more-severe invertase-repressive conditions in a synchronous chemostat culture. Both the intracellular glucose-6-phosphate concentration and residual glucose concentration were significantly higher in synchronous chemostat cultures than in asynchronous chemostat cultures. In the asynchronous and synchronous continuous cultures of S. cerevisiae, about 40% of the invertase was released into the culture liquid; it has generally been believed that S. cerevisiae releases only about 5% of its invertase. In contrast to invertase production and localization in the chemostat cultures of S. cerevisiae, no significant changes in inulinase (EC 3.2.1.7) production and localization were observed in chemostat cultures of Kluyveromyces maxianus CBS 6556. In cultures of K. marxianus about 50% of the inulinase was present in the culture liquid.

Production, Distribution, and Kinetic Properties of Inulinase in Continuous Cultures of Kluyveromyces marxianus CBS 6556.

From a screening of several Kluyveromyces strains, the yeast Kluyveromyces marxianus CBS 6556 was selected for a study of the parameters relevant to the commercial production of inulinase (EC 3.2.1.7). This yeast exhibited superior properties with respect to growth at elevated temperatures (40 to 45 degrees C), substrate specificity, and inulinase production. In sucrose-limited chemostat cultures growing on mineral medium, the amount of enzyme decreased from 52 U mg of cell dry weight at D = 0.1 h to 2 U mg of cell dry weight at D = 0.8 h. Experiments with nitrogen-limited cultures further confirmed that synthesis of the enzyme is negatively controlled by the residual sugar concentration in the culture. High enzyme activities were observed during growth on nonsugar substrates, indicating that synthesis of the enzyme is a result of a derepression/repression mechanism. A substantial part of the inulinase produced by K. marxianus was associated with the cell wall. The enzyme could be released from the cell wall via a simple chemical treatment of cells. Results are presented on the effect of cultivation conditions on the distribution of the enzyme. Inulinase was active with sucrose, raffinose, stachyose, and inulin as substrates and exhibited an S/I ratio (relative activities with sucrose and inulin) of 15 under standard assay conditions. The enzyme activity decreased with increasing chain length of the substrate.