Usefulness of continuous air tonometry for evaluation of splanchnic perfusion during cardiopulmonary bypass

Although gastric mucosal tonometry has been reported as a useful method to assess splanchnic perfusion during cardiovascular surgery, the conventional discontinuous method of tonometry (saline tonometry) was cumbersome and prone to systematic errors. A new automated system of air tonometry (Tonocap; Datex Ohmeda, Helsinki, Finland) allows for frequent (every 10 minutes) measurement of gastric regional CO2 (PrCO2) and may be more suitable as a monitoring system in cardiac patients. We evaluated the usefulness of continuous air tonometry as a marker of splanchnic perfusion during cardiopulmonary bypass (CPB). In 19 patients (53-79 years, mean 63 years) who underwent cardiovascular surgery under standard CPB with mild hypothermia (32 degrees C) from January 2001 to May 2002, the PrCO2 and calculated intramucosal pH (pHi) of gastric tonometry was monitored using Tonocap, and their relation to postoperative visceral organ function was evaluated. The pHi significantly increased after initiation of CPB from 7.32 +/- 0.07 to 7.43 +/- 0.10 (p < 0.05) and then consistently decreased in all patients to 7.39 +/- 0.09 at the end of CPB. The value of PrCO2 significantly (p < 0.01) correlated with the value of pHi. The lowest value of pHi during CPB was significantly related to blood urea nitrogen (r = -0.75, p < 0.05), serum creatinine (r = -0.78, p < 0.05), creatinine clearance (r = 0.68, p < 0.05) on postoperative day 1, and blood urea nitrogen (r = -0.84, p < 0.01) on day 3. In contrast, arterial blood lactate level, venous oxygen saturation, and routinely measured hemodynamics (e.g., pump flow, arterial pressure) during CPB were unrelated to the postoperative visceral organ function. These results suggest that continuous monitoring of gastric regional CO2 and pHi by air tonometry system is useful for the evaluation of splanchnic perfusion during CPB and may contribute to improve CPB technique by allowing the early detection of visceral malperfusion.     

Oriented properties of the chlorophylls: Electronic absorption spectroscopy of orthorhombic pyrochlorophyllide a-apomyoglobin single crystals

The orientations of the transition dipole moments in chlorophyll (Chl) are among the most useful spectroscopic properties for determining macromolecular architecture in photosynthetic complexes; however, the relationships between these orientations and the Chl molecular geometry are unknown. In order to solve this problem, we have prepared single crystals of the synthetic 1:1 complex between pyrochlorophyllide a and apomyoglobin. The protein crystallizes readily in the orthorhombic (B) form, space group P2₁2₁2₁, and the unit cell dimensions are determined to be within 0.5% of those for native MetMb crystals of the same type. These green crystals are highly dichroic, and the strong absorption along the crystallographic a axis in the Q_y band is red-shifted by about 9 nm, relative to the corresponding feature in a solution of the protein. Although the crystal structure for native Mb in this space group has not been determined, the direction cosines of the heme normal relative to the crystal axes have been measured. By using these values, an appropriate trigonometric analysis, and the measured polarized single-crystal spectra, the orientation of the Chl transition dipole moment for the Q_y transition can be specified relative to the crystal axes. With the completion of the protein crystal structure, this result will lead directly to the orientations of the optical transition dipole moments relative to the molecular geometry. The effects of vibronic coupling and the protein environment on the absorption properties of Chl are discussed in detail.     

Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats

The modifying effect of dietary administration of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They also received diets containing 100 or 500 p.p.m. auraptene for 5 weeks, starting 1 week before the first dose of AOM. At termination of the study (week 5) dietary administration of auraptene caused a significant reduction in the frequency of ACF in a dose- dependent manner (P < 0.05). Feeding of auraptene suppressed expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling- index, ornithine decarboxylase activity, polyamine content and number of silver stained nucleolar organizer region protein particles) in the colonic mucosa and the occurrence of micronuclei caused by AOM. Also, auraptene increased the activities of phase II enzymes (glutathione S- transferase and quinone reductase) in the liver and colon. These findings might suggest that inhibition of AOM-induced ACF may be associated, in part, with increased activity of phase II enzymes in the liver and colon and suppression of cell proliferation in the colonic mucosa.      

Absence of jolt accentuation of headache cannot accurately rule out meningitis in adults

BackgroundMeningitis is a common emergency disease. Signs and symptoms easily observed at the bedside are needed because early recognition of the possibility of meningitis is necessary for the decision to perform lumbar puncture. Jolt accentuation of headache has been reported to be the most sensitive diagnostic test; however, limited articles have reproduced its sensitivity.MethodsThis is a single-center retrospective medical record review between 2007 and 2012. We diagnosed meningitis based on the criterion standard that cerebrospinal fluid total cells is more than 5/mm³, in accordance with previous studies. All diagnostic and management decisions including Kernig sign, nuchal rigidity, and jolt accentuation of headache were at the physician's discretion. We calculated the sensitivity and specificity of well-known signs and symptoms of meningitis and, especially, compared the efficacy of jolt accentuation of headache with previous studies.ResultsWe investigated 531 adult patients who were suspected of meningitis and had lumbar puncture performed. Of these patients, 139 had meningitis. Background characteristics and vital signs were not clinically different between the 2 groups, although classic tetralogy of bacterial meningitis (fever, nuchal rigidity, mental disturbance, and headache) was worth investigated. The sensitivity and specificity of jolt accentuation of headache were 63.9% (95% confidence interval, 51.9%-76.0%) and 43.2% (34.7%-51.6%), respectively.ConclusionThe absence of jolt accentuation of headache test cannot, on its own, accurately rule out meningitis in adults. Further studies are warranted to reproduce this result and to discover better bedside diagnostic tests.     

Clinical evaluation of local administration of RIL-2 in head and neck cancer

Recombinant Interleukin-2 (rIL-2) was administered locally to 20 patients with head and neck cancer. 800 thousand units of TGP-3 were injected around the tumor mass every day for about 4 weeks. Complete response (CR) was obtained in two cases with lip cancer and one with lingual cancer showed partial response (PR), and minor response (MR) in oral floor cancer. No recurrence of tumors was observed in the two cases of lip cancer. Chemotherapy was performed with rIL-2 in cases responding only insufficiently to rIL-2. It was interesting that arterial infusion of anticancer drugs subsequent to local administration of rIL-2 resulted in a dramatic decrease in tumor size in a short time. It is suggested that local administration of rIL-2 may play an important role in multimodal treatment for head and neck cancer.     

Auraptene, a Citrus Coumarin, Inhibits 12-0-Tetradecanoylphorbol-13-acetate-induced Tumor Promotion in ICR Mouse Skin, Possibly through Suppression of Superoxide Generation in Leukocytes

Coumarin-related compounds, auraptene and umbelliferone, have been isolated from the cold-pressed oil of natsumikan (Citrus natsudaidai HAYATA), and tested as inhibitors of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in Raji cells. The 50% inhibitory concentration (IC₅₀) of auraptene (18μ M )was almost equal to that of genistein. Umbelliferone, which lacks a geranyloxyl group present in auraptene, was less active (IC₅₀=450 μ M ). In a two-stage carcinogenesis experiment with 7, 12-dimethylbenz[α]anthracene (topical application at 0.19 μmol) and TPA (topical application at 1.6 nmol) in ICR mouse skin, topical application of auraptene (at 160 nmol) significantly reduced tumor incidence and the numbers of tumors per mouse by 27% ( P < 0.01) and 23% ( P < 0.05), respectively. Auraptene at a concentration of 50 μ M markedly suppressed superoxide (O₂⁻) generation induced by 100 n M TPA in differentiated human promyelocytic HL-60 cells. Having no O₂⁻ -scavenging potential, auraptene may inhibit the multicomponent NADPH oxidase system. Inhibition of intracellular hydroperoxide formation in differentiated HL-60 cells by auraptene was also confirmed by flow-cytometric analysis using 2',7'-dichlorofluorescein diacetate as a fluorescence probe. Quantitative analyses using high-performance liquid chromatography showed the occurrence of auraptene not only in both the peels and sarcocarps of natsumikan , but also in those of hassaku orange ( C. hassaku ) and grapefruit (C. paradisi ,) and even in their bottled fresh juice form. These results indicate that auraptene is a chemopreventer of skin tumorigenesis, and implies that suppression of leukocyte activation might be the mechanism through which it inhibits tumor promotion.     

Restorative effects of calmodulin antagonists on reduced cisplatin uptake by cisplatin-resistant human ovarian cancer cells

In the present study, we attempted to determine effects of calmodulin antagonists (W-7 and W-5) on cisplatin uptake by human ovarian cancer cells, using KF cells derived from serous cystadenocarcinoma of the ovary and cisplatin-resistant cells (KFr). The degree of cisplatin resistance of the KFr cells was about 3.7-fold higher than that of the parent KF cells, with regard to the concentration of cisplatin required for 50% inhibition of cell proliferation (IC50). When KF and KFr cells were incubated with 10 micrograms/ml cisplatin for 4 hr, cisplatin-content in the KF cells was significantly higher than that in the KFr cells. When KF cells were incubated in the presence of W-7 (but not W-5), cisplatin uptake significantly increased, compared to cells treated with cisplatin alone. On the other hand, when KFr cells were incubated in the presence of 5 micrograms/ml W-7 or W-5, cisplatin uptake was significantly higher than uptake by KFr cells treated with cisplatin alone, being comparable to that by KF cells treated with cisplatin alone. Such an increase in cisplatin uptake seemed to bring about adjuvant effects to cisplatin of KFr cell proliferation in vitro. The KF tumor grown in nude mice took up 24.8 ng/g dry wt of cisplatin 4 hr after intraperitoneal administration. When cisplatin was administered with calmodulin antagonists, cisplatin uptake by the KF and KFr tumors was significantly increased, compared to that after treatment with cisplatin alone. In particular, the cisplatin uptake by the KFr tumor was about 2.5-fold higher than that by the KFr tumor treated with cisplatin alone. These results suggest that coadministration of calmodulin antagonists and cisplatin may be of use in patients with refractory ovarian cancer.