Intraoperative oliguria predicts acute kidney injury after major abdominal surgery.

Background: The threshold of intraoperative urine output below which the risk of acute kidney injury (AKI) increases is unclear. The aim of this retrospective cohort study was to investigate the relationship between intraoperative urine output during major abdominal surgery and the development of postoperative AKI and to identify an optimal threshold for predicting the differential risk of AKI. Methods: Perioperative data were collected retrospectively on 3560 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or oesophageal resection) at Kyoto University Hospital. We evaluated the relationship between intraoperative urine output and the development of postoperative AKI as defined by recent guidelines. Logistic regression analysis was performed to adjust for patient and operative variables, and the minimum P -value approach was used to determine the threshold of intraoperative urine output that independently altered the risk of AKI. Results: The overall incidence of AKI in the study population was 6.3%. Using the minimum P -value approach, a threshold of 0.3 ml kg -1 h -1 was identified, below which there was an increased risk of AKI (adjusted odds ratio, 2.65; 95% confidence interval, 1.77-3.97; P <0.001). The addition of oliguria <0.3 ml kg -1 h -1 to a model with conventional risk factors significantly improved risk stratification for AKI (net reclassification improvement, 0.159; 95% confidence interval, 0.049-0.270; P =0.005). Conclusions: Among patients undergoing major abdominal surgery, intraoperative oliguria <0.3 ml kg -1 h -1 was significantly associated with increased risk of postoperative AKI.

Validation experiment of a numerically processed millimeter-wave interferometer in a laboratory.

We propose a new interferometer system for density profile measurements. This system produces multiple measurement chords by a leaky-wave antenna driven by multiple frequency inputs. The proposed system was validated in laboratory evaluation experiments. We confirmed that the interferometer generates a clear image of a Teflon plate as well as the phase shift corresponding to the plate thickness. In another experiment, we confirmed that quasi-optical mirrors can produce multiple measurement chords; however, the finite spot size of the probe beam degrades the sharpness of the resulting image.

Cytokine profile during the clinical course of toxic shock syndrome.

Toxic shock syndrome (TSS) is an acute febrile disease with multiple organ involvement caused by massive and rapid release of cytokines induced by staphylococcal exotoxins. However, the precise cytokine profile is still undefined in clinical cases. We measured serum cytokine concentrations in a patient who developed TSS after a caesarean section. Measurements were taken on admission and several times during the course of the disease. Methicillin-resistant Staphylococcus aureus producing TSS toxin-1 and staphylococcal enterotoxin C was detected in the lochia and venous blood. Serum interleukin (IL)-6 level was markedly increased on admission, and IL-10, tumour necrosis factor-alpha, and interferon-gamma levels were also raised. These cytokine levels rapidly returned to normal levels. In contrast, IL-1beta and IL-2 were below the analytical sensitivity threshold throughout the course. Our data and other previous case reports indicate that a marked increase in IL-6 concentration could be a clinical marker of TSS onset.

Gelation mechanism of surimi studied by 1h NMR relaxation measurements.

In order to elucidate the gelation mechanism of surimi, the temperature dependence of water proton spin-spin relaxation time ((1)H T(2)) has been described by a theoretical approach, in which the exposed protein surface is taken into account. Water (1)H T(2) measured for horse mackerel surimi in the presence of 2.5% NaCl was analyzed on the basis of the consideration for the denaturation and the aggregation of protein in order to explain the macroscopic structural change during the heating and the cooling processes. The temperature dependence of water (1)H T(2) and the fraction of rigid component gave a clear explanation for the gelation mechanism of surimi. Differential scanning calorimetry thermogram and dynamic viscoelastic measurements supported the results of nuclear magnetic resonance (NMR) measurements. It has been demonstrated that the measurement of NMR relaxation times is useful to describe the gelation mechanism of surimi.

Comparison between tube compensation and pressure support ventilation techniques on respiratory mechanics.

In the intubated patient, the presence of an endotracheal tube increases the work of breathing during spontaneous breathing. The tube compensation technique was developed as a new ventilator mode that can compensate for that additional the work of breathing. We investigated the respiratory parameters during the pressure support ventilation 0, 5, 10 cmH2O and tube compensation 100% modes of the Puritan Bennett 840 ventilator in ten postoperative patients who had undergone radical surgery for oesophageal cancer. Measurements were performed just before extubation. The tidal volume, respiratory rate and other respiratory parameters were measured with a Ventrak respiratory monitor, and the duty ratio, mean inspiratory flow, and rapid shallow breathing index were calculated. In particular, we performed a comparison between pressure support ventilation 5 cmH2O and tube compensation 100%, because pressure support ventilation 5 cmH2O is the usual ventilating mode before the extubation in our intensive care unit. The tidal volume of pressure support ventilation 10 cmH2O was significantly larger and the respiratory rate was significantly lower than the other three modes. There was no significant difference in the minute volume, tidal volume, and respiratory rate between pressure support ventilation 5 cmH2O and tube compensation 100%. The duty ratio of pressure support ventilation 10 cmH2O was significantly smaller than the other three modes. There was no significant difference in the duty ratio and rapid shallow breathing index between pressure support ventilation 5 cmH2O and tube compensation 100%. It was concluded that the assist levels of pressure support ventilation 5 cmH2O and tube compensation 100% were almost equal for clinical purposes.

Differences in respiratory parameters during continuous positive airway pressure and pressure support ventilation in infants and children.

The extubation criteria of pressure support ventilation (PSV) in infants and children were not yet established. We studied the differences in respiratory parameters during continuous positive airway pressure (CPAP) using a constant flow type ventilator and PSV using a demand valve type ventilator. Nineteen children (1.9+/-2.9 years old) who were ready to extubate were studied. All patients had recovered from their respiratory failure and had finished the weaning process of the ventilatory support. They were scheduled for extubation on the next day when their ventilatory mode had attained to a PSV of 3 cmH2O with a positive end-expiratory pressure (PEEP) of 3 cmH2O. On the extubation day, tidal volume (TV) and respiratory frequency (RR) were measured with a respiratory monitor at two modes (CPAP of 3 cmH2O and PSV), and the duty ratio (DR) and mean inspiratory flow (MF) were calculated. The sequence of the ventilatory mode was random. No case required reintubation. TV was 61.6+/-54.9 during CPAP and 67.7+/-61.4 ml during PSV, and RR was 38.5+/-10.6 and 37.1+/-8.8 beats/min., respectively. DR was 0.382+/-0.067 and 0.359+/-0.085, and MF was 96.6+/-78.3 and 101.0+/-69.0 ml/sec., respectively. The measured parameters and calculated values showed no significant difference between CPAP and PSV. It was found that the respiratory parameters were almost the same with CPAP and PSV immediately before the extubation, and the previous extubation criteria of CPAP can be used.

The effects of organ resection on rat urinary bladder carcinogenesis.

The effect of unilateral nephrectomy, orchiectomy or partial hepatectomy on the growth of chemically induced rat bladder tumors was investigated. Male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 5 weeks, and surgical resection of one of these organs was performed 2 weeks after the completion of BBN administration. Histological evaluation of the bladder 24 weeks after the start of the experiment revealed that unilateral nephrectomy and orchiectomy significantly increased the numbers of preneoplastic and neoplastic lesions as compared with the corresponding sham-operated groups. Partial hepatectomy also enhanced tumor growth, although not significantly. Immunohistochemical studies examining the effect of organ resection on normal bladder urothelium showed that BrdU immunostaining of urothelial cells significantly increased 7 days after unilateral nephrectomy or orchiectomy, while BrdU incorporation was minimum after partial hepatectomy or sham operation. C-met expression in the bladder urothelium was evident following unilateral nephrectomy or partial hepatectomy, while increased immunoreactivity of androgen receptor was noted following unilateral orchiectomy. Further study is needed to determine the exact mechanism of the bladder tumor growth-enhancing effect associated with organ restriction.

Granulocyte colony-stimulating factor (G-CSF)-mediated signaling regulates type IV collagenase activity in head and neck cancer cells.

Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine, regulates the proliferation and differentiation of granulocytic progenitor cells and functionally activated mature neutrophils. G-CSF also affects nonhematopoietic tumor cells through its binding to the specific receptor (G-CSFR) on the cells. The type IV collagenase [matrix metalloproteinase 2 (MMP-2)] is known to play a main role in the process of invasion and metastasis, but its regulation, for example, in expression or in activation, is not clearly understood. In this study, we investigated the role of G-CSF in the regulation of tumor cell invasion and the synthesis of MMP-2. G-CSFs producing the head and neck carcinoma cell line T3M-1 cells with metastatic ability and no G-CSF receptor (G-CSFR) expression were transfected with G-CSFR expression vector. In vitro treatment of G-CSFR-transfectant T3M-1 cells with recombinant G-CSF (rG-CSF) significantly augmented their invasive potential in a reconstituted basement membrane (Matrigel) system compared with that of parental cells. Moreover, MMP-2 activity of G-CSFR-transfectant T3M-1 cells was enhanced by the stimulation with rG-CSF, as assessed by gelatin zymography. These results identify G-CSF as a regulator of MMP-2 and cellular invasion.

Highly selective one-pot synthesis of spirophosphoranes exhibiting reversed apicophilicity by oxidation of dianions generated from P-H spirophosphorane.

[see reaction]. Mild and highly selective one-pot procedures for obtaining phosphoranes that exhibit reversed (O-cis) apicophilicity are described. On the basis of the procedures, O-cis phosphorane bearing an aryl group (R = 2,4,6-tri-i-propylphenyl) could be isolated for the first time; the procedure is also applicable for alkyl derivatives. Particularly effective was the use of I2 as an oxidizing reagent.

Hyperbaric oxygen therapy given 30 minutes after spinal cord ischemia attenuates selective motor neuron death in rabbits.

OBJECTIVE: Spinal cord ischemia sometimes causes paraplegia because the spinal motor neuron cells are vulnerable to ischemia. Although various protective remedies for spinal cord injury have been reported, there have been few established clinical methods. Although hyperbaric oxygen (HBO) has been used clinically as a treatment for ischemia, the reason for its effectiveness is still uncertain because sufficient experimental data are lacking. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal research laboratory in a university research center. SUBJECTS: Twenty-three Japanese white rabbits, weighing 2-3 kg. INTERVENTIONS: A modified rabbit spinal cord ischemia model of infrarenal aortic occlusion for 15 mins was employed. Rabbits were randomly assigned to four groups; the rabbits in group A did not undergo ischemic insults (n = 5). The rabbits in groups B and C underwent ischemic insult for 15 mins, followed by 1 hr of HBO treatment at 3 atm absolute with 100% oxygen at 30 mins (n = 6) or 6 hrs (n = 7) after reperfusion, respectively. The rabbits in group D underwent ischemic insult for 15 mins without HBO treatment (n = 5). MEASUREMENTS AND MAIN RESULTS: We observed neurologic functions for 14 days. The sections of the spinal cords were stained with hematoxylin and eosin, and the number of spinal motor neurons in ventral region was counted by light microscopy. All rabbits in groups A and B could stand, whereas all rabbits in groups C and D showed irreversible paraplegia on days 2 and 14 after reperfusion. Spinal motor neurons in ventral gray matter in groups C and D decreased significantly compared with those in groups A and B. CONCLUSIONS: HBO therapy shortly after ischemic insult had protective effects against ischemic spinal cord damage. However, delayed treatment with HBO did not change the prognosis.

Evaluation of tube compensation in the Bennett 840 ventilator--a new ventilatory mode to support spontaneous breathing.

Respiratory care patients frequently require intubation with an endotracheal tube (ETT). Unfortunately, the ETT introduces a pressure drop (deltaPETT) that depends on the respiratory flow rate, thus increasing the work of breathing (WOB). Pressure support ventilation (PSV) cannot adequately compensate for this added WOB, because the degree of inspiratory assistance by PSV is fixed. Therefore, a technique called tube compensation (TC) has been developed to address deltaPETT. We examined the performance of TC and compared it with PSV of 5 cm H2O. The experimental system was constructed from a simulator, a test-lung, flow sensors, and a Bennett 840, and the respiratory parameters were studied. ETTs with IDs 6.5 and 8.0 mm were used. The quadratic approximation obtained for deltaPETT in the 6.5-mm ETT was 2.316 x flow + 7.910 x flow2, while that for the 8.0-mm ETT was 1.881 x flow + 3.353 x flow2. The maximum inspiratory flow (MIF) increased significantly with increasing TC, but tidal volume and inspiratory time did not show marked changes. The MIF for TC of 100% was larger than that for PSV of 5 cm H2O, when the 6.5-mm ID was used, but there was no significant difference between these modes when an ID of 8.0 mm was used. For both the 6.5 and 8.0-mm IDs, the PV loop corresponding to 100% TC was larger than that for PSV of 5 cm H2O. TC only compensated for the WOB caused by the ETT, whereas PSV compensated for the WOB caused by the ETT and the demand valve system. In clinical use, the differences between TC and PSV will demand attention.

Selective uptake by cancer cells of liposomes coated with polysaccharides bearing 1-aminolactose.

We investigated the selective uptake of liposomes chemically modified by polysaccharides-cholesterol derivatives with 1-aminolactose (lactose) in two human hepatoma cell lines (HUH7 and Alexander), a human colon cancer cell line (FCC) and a human lung cancer cell line (KNS). The uptakes of the labeled liposomes alone (conventional liposomes), those with cholesterol pullulan (CHP) and with lactose (lactose CHP) were compared in four cancer cells and normal rat hepatocytes after 3 hours of incubation. The radioactivities of the lactose CHP were 4.4, 4, 3.4 and 4.4 times greater than those of CHP in HuH7, Alexander, FCC and KNS cells, respectively, after 3 hours of incubation. All the above differences were statistically significant (p < 0.01). No statistically significant differences were seen in the case of hepatocytes. Thus, cancer cells have a common affinity with lactose CHP liposomes, however, these mechanisms appear to have no connection with the galactose-specific asialoglycoprotein receptors of hepatocytes.

P-ANCA-positive Wegener's granulomatosis presenting with hypertrophic pachymeningitis and multiple cranial neuropathies: case report and review of literature.

An autopsy case of hypertrophic pachymeningitis and multiple cranial neuropathies is reported. A 53-year-old woman with paraplegia and various neurological signs which developed over a 2 year period was diagnosed as having an epidural mass with thickened dura mater extending from the lower cervical to the thoracic spinal cord. In addition, bilateral episcleritis, blephaloptosis, and blindness of the right eye with various cranial nerve deficits were found to be caused by the mass lesions involving the paranasal sinuses, orbit, and the cavernous sinus. Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) was positive, but cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) was negative by enzyme-linked immunosorbent assay. The partially removed epidural mass with hypertrophied dura mater and biopsy of the paranasal lesions showed chronic granulomatous inflammation with vasculitis. The remaining lesions resolved with steroid therapy with remarkable neurological improvement. The positive p-ANCA test, paranasal involvement, the report of a similar histopathological case and a review of the literature on granulomatous pachymeningitis suggest the presence of p-ANCA-positive Wegener's granulomatosis with central nervous system involvement characterized by hypertrophic pachymeningitis and/or multiple cranial neuropathies.

Enantiomer-selective activation of racemic catalysts.

Asymmetric catalysts can be evolved into highly activated catalysts by association with chiral activators. This asymmetric activation process is particularly useful in racemic catalysis through selective activation of one enantiomer of the racemic catalysts. Recently, a strategy whereby a racemic catalyst is selectively deactivated by a chiral additive has been reported to yield nonracemic products. However, we have reported a strategy that is an alternative to asymmetric catalysts but is conceptually opposite, in which a chiral activator selectively activates rather than deactivates one enantiomer of a racemic chiral catalyst. The advantage of this activation strategy over the deactivation counterpart is that the activated catalyst can produce a greater enantiomeric excess (x(act)% ee) in the products than the ee attained by the enantiomerically pure catalyst on its own. Therefore, 'asymmetric activation' could provide a general and powerful strategy for the use of not only atropisomeric and, hence, racemic ligands but also chirally flexible and 'pro-atropisomeric' ligands without enantiomeric resolution!

Comparison of non-tryptophan fluorophores in protein-free extract of brunescent and non-brunescent human cataract.

PURPOSE: To investigate whether any of the fluorophores in the human lens nuclei might be responsible for human brunescent cataract formation. METHODS: Human lens nuclei (non-brunescent, from 13; brunescent, from 8) were obtained after extracapsular cataract extraction in nondiabetic patients. Protein-free extract, prepared by filtrating the water-soluble fraction of each nucleus through a centrifugal ultrafilter (molecular weight < 5,000), was analytically separated by high-performance liquid chromatography. RESULTS: No significant differences between non-brunescent and brunescent nuclei were observed in the concentrations (mean +/- SD) of 3-hydroxykynurenine O-beta-glucoside (0.67 +/- 0.38 vs. 0.85 +/- 0. 62 micromol/g wet weight), 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-glucoside (4.1 x 10(5) +/- 2.9 x 10(5) vs. 6.3 x 10(5) +/- 5. 0 x 10(5) area unit/g wet weight), and kynurenine (0.016 +/- 0.011 vs. 0.029 +/- 0.021 micromol/g wet weight). A novel fluorophore that has not been identified so far was significantly present more in brunescent than in non-brunescent nuclei (brunescent: 1.5 x 10(5) +/- 1.0 x 10(5) vs. non-brunescent: 2.6 x 10(3) +/- 6.3 x 10(3) area unit/g wet weight, P <.01). Digestion of the protein-free extract with beta-glucosidase eliminated the peak corresponding to the novel unidentified fluorophore. CONCLUSION: The present results imply a novel protein-unbound fluorophore, presumably a beta-glucoside, might possibly be involved in brunescent cataract formation.

Leukotoxin, 9,10-epoxy-12-octadecenoate, causes pulmonary vasodilation by stimulation of vascular eNOS and iNOS.

We have previously reported that leukotoxin, 9,10-epoxy-12-octadecenoate (Lx) dilates rat pulmonary arteries by means of nitric oxide synthase (NOS) activation. In this study, we investigated if Lx stimulates constitutive and/or inducible NOS. We studied the effect of the NOS inhibitors, N(G)-monomethyl-L-arginine and aminoguanidine, as well as endothelium denudation on Lx-induced rat pulmonary arterial dilation and that of aminoguanidine on Lx-induced endothelium denuded lipopolysaccharide (LPS)-treated rat pulmonary arterial dilation and tissue cGMP content. Furthermore, we assessed the effect of aminoguanidine, an inducible NOS (iNOS) inhibitor, on the cGMP content increase induced by Lx in LPS-treated human pulmonary artery smooth muscle cells (HPASMC). The NOS inhibitors and endothelium denudation significantly attenuated Lx-induced vasodilation. Aminoguanidine also significantly attenuated Lx-induced vasodilation in LPS-treated rat denuded pulmonary arteries, and attenuated Lx-induced cGMP content increase in denuded pulmonary arterial rings from LPS-treated rats and in LPS-treated HPASMC. These results suggest that Lx causes pulmonary vasodilation by stimulation of vascular endothelial NOS (eNOS) and iNOS.

Effect of Ca(2+)-independent mechanisms on the hypoxic relaxation of guinea-pig tracheal rings.

Hypoxia induces bronchodilation in vivo and in vitro, but the mechanisms are still unclear. To evaluate whether an extra- or intracellular free Ca(2+) ion is involved in the mechanisms of hypoxic relaxation, we simultaneously measured cytosolic Ca(2+)levels and tensions in both intact and denuded guinea-pig tracheal strips precontracted with histamine (100 microM), and assessed the effect of hypoxia on guinea-pig tracheal rings precontracted with okadaic acid (10 microM) and calyculin-A (0.1 approximately 10 microM) under an extracellular Ca(2+)-free state. The exposure of tracheal rings to hypoxia induced an immediate decrease of tracheal tension without decrease in intracellular free Ca(2+)levels. In the presence of okadaic acid but not calyculin-A, hypoxic air exposure caused significant transient reductions in tracheal tone. Further, thapsigargin (5 microM or 10 microM) did not affect hypoxic bronchodilation, suggesting that the release of intracellular Ca(2+) does not take a role in hypoxic bronchodilation. Hypoxic dilation decreased ATP content in epithelium-intact rings but not epithelium-denuded rings, indicating a relationship between hypoxic dilation and change of adenine nucleotide in epithelium-intact rings. Our findings indicate that the epithelium dependent mechanisms of hypoxic relaxation of guinea pig tracheal rings preconstricted with histamine may not be related to the mobilization of extra and intra-cellular Ca(2+).

[Anesthetic management of a patient with hemophilia A for left modified Blalock-Taussig shunt].

We gave anesthesia to a patient with hemophilia A for left modified Blalock-Taussig shunt. The patient was a twenty five-day-old boy with pulmonary atresia. We performed the bolus injection test of factor VIII concentrate in preoperative period. His factor VIII activity increased from 9.3 to 113.3% after a bolus injection of 165 units. To keep his factor VIII activity above 80% in perioperative period, a bolus of 125 units of recombinant factor VIII concentrate was injected at anesthesia induction, 125 units 2 hours after the start of the operation, and 125 units 6 hours after the end of the operation. Factor VIII activity 2 hours after anesthesia induction increased only 37.8%, and we had to infuse recombinant factor VIII concentrate additionally. We measured factor VIII activity during operation, and he finally received total of 415 units of factor VIII concentrate. Hydroxyethyl starch infusion, blood transfusion and bleeding in the perioperative period might have caused the factor VIII activity to decrease beyond our expectation. We should infuse factor VIII concentrate properly measuring the factor VIII activity during this operation.

Changes in expression of mRNAs in the gerbil hippocampus following transient forebrain ischemia.

The phenomenon of delayed neuronal death in CA1 neurons following brief duration of global ischemia has eluded definitive explanation. Using a differential display technique, we examined changes in expression of mRNAs in the hippocampus following 5-min cerebral ischemia in Mongolian gerbils. Under pentobarbital anesthesia, gerbils were sacrificed by decapitation at 6 h (n = 20) and 2 days (n = 20) after ischemia, and sham-operated gerbils (n = 20) were sacrificed at 6 h after surgery. Total RNA was isolated from the hippocampal samples in each group for the differential display analysis. The mRNAs were classified into three patterns; gradual disappearance, decrease and recovery, and new appearance. Representative mRNAs in three patterns were subcloned and sequenced partly. An mRNA in the gradual disappearance pattern showed homologous with neuronal pentraxin. In situ hybridization and Northern blot analyses of neuronal pentraxin revealed the gradual disappearance pattern. An mRNA in the decrease and recovery pattern showed homologous with 14-3-3 protein gamma-subtype, and an mRNA in the new appearance pattern showed no homology in the data base. The differential display analysis is a useful technique with which to investigate changes in expression of mRNAs following transient cerebral ischemia. The novel mRNA may be involved in the treatment of cerebral ischemia. Further studies are necessary for this point.