Clinical study of a new skin antiseptic olanexidine gluconate in gastrointestinal cancer surgery.

BACKGROUND: Surgical site infection (SSI) is a common complication of gastrointestinal surgery. Olanexidine gluconate (OLG) is a novel skin antiseptic that is effective against a wide range of bacteria. The purpose of this study was to evaluate the bactericidal efficacy of OLG in gastrointestinal cancer surgery. METHODS: This retrospective study included a total of 281 patients who underwent gastrointestinal cancer surgery (stomach or colon). The patients were divided into two groups: 223 patients were treated with OLG (OLG group), and 58 patients were treated with povidone-iodine (PVP-I) (control group). The efficacy and safety outcomes were measured as the rate of SSI within 30 days after surgery. In addition, we conducted subgroup analyses according to the surgical approach (open or laparoscopic) or primary lesion (stomach or colon). RESULTS: There was a significant difference in the rate of SSI between the control group and OLG group (10.3% vs. 2.7%; p = 0.02). There was a significant difference in the SSI rate in terms of superficial infection (8.6% vs. 2.2%; p = 0.0345) but not in deep infection (1.7% vs. 0.5%; p = 0.371). There was no significant difference between the control group and OLG group in the overall rate of adverse skin reactions (5.2% vs. 1.8%; p = 0.157). CONCLUSION: This retrospective study demonstrates that OLG is more effective than PVP-I in preventing SSI during gastrointestinal cancer surgery.

Pt thermal atomic layer deposition for silicon x-ray micropore optics.

We fabricated a silicon micropore optic using deep reactive ion etching and coated by Pt with atomic layer deposition (ALD). We confirmed that a metal/metal oxide bilayer of Al2O3∼10 nm and Pt ∼20 nm was successfully deposited on the micropores whose width and depth are 20 µm and 300 µm, respectively. An increase of surface roughness of sidewalls of the micropores was observed with a transmission electron microscope and an atomic force microscope. X-ray reflectivity with an Al Kα line at 1.49 keV before and after the deposition was measured and compared to ray-tracing simulations. The surface roughness of the sidewalls was estimated to increase from 1.6±0.2 nm rms to 2.2±0.2 nm rms. This result is consistent with the microscope measurements. Post annealing of the Pt-coated optic at 1000°C for 2 h showed a sign of reduced surface roughness and better angular resolution. To reduce the surface roughness, possible methods such as the annealing after deposition and a plasma-enhanced ALD are discussed.

Relationship between the matrix effect and the physicochemical properties of analytes in gas chromatography.

The phenomenon "matrix-induced chromatographic response enhancement" (matrix effect) causes quantitative errors in gas chromatography (GC) analyses. This effect varies according to the analyte nature, matrix type and concentration, and GC-system parameters. By focusing on the physicochemical properties of analytes, a predictive model was developed for the matrix effect using quantitative structure-property relationships. Experimental values of the matrix effect were determined for 58 compounds in a serum extract obtained from solid-phase extraction as the matrix. Eight molecular descriptors were selected, and the matrix-effect model was developed by multiple linear regression. The developed model predicted values for the matrix effect without any further experimental measurements. It also indicated that the molecular polarity (particularly H-bond donors) and volume of the analyte increase the matrix effect, while hydrophobicity and increasing number of nonpolar carbon atoms in the analyte decrease the matrix effect. The model was applied to the analysis of barbiturates. The predicted values indicated that N-methylation decreases the matrix effect, and the relative predicted values were effective for the selection of an internal standard. The obtained insight into the matrix effect and the prediction data will be helpful for developing quantitative analysis strategies.

A new procedure for temporary auxiliary partial liver transplantation using living donor graft for patients with familial amyloid polyneuropathy.

To introduce duct-to-duct biliary anastomosis to conventional temporary auxiliary partial orthotopic liver transplantation (APOLT) using living donor graft for patients with familial amyloid polyneuropathy, we modified the conventional APOLT procedure in a manner characterized by the use of the recipient's common hepatic duct for biliary reconstruction and the preservation of the right posterior section alone for the certain placement of a tube into the corresponding biliary tree for external biliary drainage (modified APOLT). This procedure was performed in 3 patients without biliary complications. No complications associated with the external drainage tube occurred. Here we report the techniques and results for this new procedure.

Determination of dextromethorphan in human plasma using pipette tip solid-phase extraction and gas chromatography-mass spectrometry.

Dextromethorphan was extracted from human plasma samples (100 µL) using MonoTip C(18) tips, which are packed with C(18)-bonded monolithic silica gel that is attached to the inside of the tip. The samples, which contained dextromethorphan and trimeprazine as an internal standard (IS), were mixed with 200 µL of distilled water and 50 µL of 1 mol/L glycine-sodium hydroxide buffer (pH 10). The mixture was extracted to the C(18) phase of the tip by 20 sequential aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C(18) phase were then eluted with methanol by five sequential aspirating/dispensing cycles. The eluate was injected directly into a gas chromatograph and detected by a mass spectrometer with selected ion monitoring in positive electron ionization mode. An Equity-5 fused silica capillary column (30 m × 0.32 mm i.d., film thickness 0.5 µm) gave adequate separation of the dextromethorphan, IS, and impurities. The recoveries of dextromethorphan and the IS spiked into plasma were >87.4%. The regression equation for dextromethorphan showed excellent linearity from 2.5 to 320 ng/mL of plasma, and the limit of detection was 1.25 ng/mL of plasma. The intraday and interday coefficients of variation were less than 10.5% and 14.7%, respectively. The accuracy ranged from 91.9% to 107%. The validated method was successfully used to quantify the plasma concentration of dextromethorphan in a human subject after oral administration of the drug.

Effects of single or repeated administrations of methamphetamine on immune response in mice.

The present study aimed to clarify the connection between immune responses and the administration frequency of methamphetamine (MAP) in male and female mice. Male and female ddY mice were given single or multiple (repeated for 10 days) intraperitoneal injections of MAP (5.0 mg/kg/day). The following immune parameters were examined; the number of leukocytes in peripheral blood and the proliferative activity (phytohemagglutinin;PHA, lipopolysaccharide; LPS response) and natural killer (NK) cell activity in splenic lymphocytes. Further, the differences in metabolic function in the spleen in response to MAP (and its metabolite amphetamine) in male and female mice were measured by gas chromatography. The results of the present study were that; 1) single and repeated MAP injections reduced leukocytes; 2) single MAP injection increased the proliferative response of splenic lymphocytes to PHA stimulation in only male mice, but the response to LPS stimulation was slightly increased in both male and female mice; 3) single and repeated MAP injections reduced NK cell activity of splenic lymphocytes, and especially in female mice with 5 injections of MAP; 4) with 10 MAP injections the NK cell activity and leukocytes recovered to the level of controls; and 5) the metabolic activity of MAP was reduced in female mice treated acutely with MAP in comparison to male mice. These results appear to indicate that immune responses to MAP were involved in the different results shown for administration frequency, sex difference and metabolic process of MAP.

A case of laparoscopic high anterior resection of rectosigmoid colon cancer associated with a horseshoe kidney using preoperative 3D-CT angiography.

BACKGROUND: Horseshoe kidney is a congenital malformation in which the bilateral kidneys are fused. It is frequently complicated by other congenital malformations and is often accompanied by anomalies of the ureteropelvic and vascular systems, which must be evaluated to avoid iatrogenic injury. We report a case of laparoscopic high anterior resection of rectosigmoid colon cancer associated with a horseshoe kidney using preoperative 3D-CT angiography. CASE PRESENTATION: A 52-year-old Japanese man with lower abdominal pain underwent lower endoscopy, revealing a type 2 lesion in the rectosigmoid colon. He was diagnosed with rectosigmoid colon cancer with multiple lung metastases and a horseshoe kidney on computed tomography (CT) scan. Three-dimensional (3D)-CT angiography showed an aberrant renal artery at the isthmus from 3 cm under the inferior mesenteric artery (IMA) branch of the aorta. Laparoscopic anterior rectal resection was performed. During the operation, the inferior mesenteric artery, left ureter, left gonadal vessels, and hypogastric nerve plexus could be seen passing over the horseshoe kidney isthmus and were preserved. The left branch of aberrant renal artery that was close to IMA was also detected and preserved. CONCLUSION: To prevent intraoperative misidentification, 3D-CT angiography should be performed preoperatively to ascertain the precise positional relationships between the extra renal arteries and the kidney. We always must consider anomalous locations of renal vessels, ureter, gonadal vessels, and lumbar splanchnic nerve to avoid laparoscopic iatrogenic injury in patients with a horseshoe kidney.

Simple and simultaneous determination for 12 phenothiazines in human serum by reversed-phase high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous analysis of the 12 phenothiazines (chlorpromazine, fluphenazine, levomepromazine, perazine, perphenazine, prochlorperazine, profenamine, promethazine, propericiazine, thioproperazine, thioridazine and trifluoperazine) in human serum using HPLC/UV. The separation was achieved using a C(18) reversed-phase column (250 mm x 4.6 mm I.D., particle size 5 microm, Inersil ODS-SP). The mobile phase, consisting of acetonitrile-methanol-30 mM NaH(2)PO(4) (pH 5.6) (300:200:500, v/v/v), was delivered at a flow rate of 0.9 mL/min and UV detection was carried out at 250 nm. The recoveries of the 12 phenothiazines spiked into serum samples were 87.6-99.8%. Regression equations for the 12 phenothiazines showed excellent linearity, with detection limits of 3.2-5.5 ng/mL for serum. The inter-day and intra-day coefficients of variation for serum samples were commonly below 8.8%. The selectivity, accuracy and precision of this method are satisfactory for clinical and forensic purposes. This sensitive and selective method offers the opportunity for simultaneous screening and quantification of almost all phenothiazines available in Japan for the purposes of clinical and forensic applications.

Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method.

A simultaneous determination of 20 antidepressant drugs (imipramine, amitriptyline, desipramine, trimipramine, nortriptyline, clomipramine, amoxapine, lofepramine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipran, sulpiride, tandspirone, methylphenidate and melitracen) in human plasma was developed using LC/MS with sonic spray ionization (SSI) method. These drugs showed good separation and sensitivity by LC-MS using an Inertsil C-8 column with methanol:10mM ammonium acetate (pH 5.0):acetonitrile (70:20:10) as mobile phase at 0.10 mL/min at 35 degrees C. Solid-phase extraction of these drugs added to the human plasma was performed with an Oasis HLB cartridge column. Recovery and limit of detection of these drugs were between 69 and 102% and between 0.03 and 0.63 microg/mL, respectively. The present procedure offers an easier and more convenient screening method for antidepressants, and will be useful for forensic toxicology investigations.

Methamphetamine-related sudden death with a concentration which was of a 'toxic level'.

We reviewed 32 cases where a forensic autopsy detected methamphetamine in the blood, and all of these autopsies were performed at two institutes between 1991 and 2003. In accordance with several criteria, the blood concentration in 11 cases was classified as above the toxic level, and 10 of these cases were diagnosed as methamphetamine poisoning. In 20 cases (62.5% of total cases), the blood concentration was of a 'toxic level', and 10, 2 and 1 of these cases were diagnosed as methamphetamine poisoning, cardiomyopathy and intracerebral hemorrhage, respectively. Since it is unclear how the effects of methamphetamine may contribute to the death of an individual, a diagnosis of the exact cause of death is often difficult to make in cases where the blood concentration of methamphetamine was of a 'toxic level'. Therefore, a diagnosis has to be carefully made in consideration of the pathological findings, the pharmacological effects of methamphetamine and the process until death in such cases. Additionally, the mechanism of methamphetamine-related death needs to be more fully studied to enable an appropriate diagnosis to be made easily.

Sensitive liquid chromatography/tandem mass spectrometry method for the simultaneous determination of nine local anesthetic drugs.

A high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) with electrospray ionization (ESI) procedure for the simultaneous determination of nine local anesthetic drugs (procaine, mepivacaine, lidocaine, ropivacaine, oxybuprocaine, tetracaine, bupivacaine, T-caine and dibucaine) in human serum is described. The chromatographic separation was performed on a Mightysil-RP-18 GP II column (2.0mm×150mm, particle size 5µm). The mobile phase consisted of 10mM acetic ammonium buffer (pH 5.4) and acetonitrile and was delivered at a flow rate of 0.20mL/min. The triple quadrupole mass spectrometer was operated in positive ion mode, and multiple reaction monitoring was used for drug quantification. Solid-phase extraction of the nine local anesthetic drugs added to the human serum was performed with an Oasis(®) HLB extraction cartridges column. The method was linear for the investigated drugs over the concentration range of 10-100ng/mL. The recoveries of these drugs were in the range of 81.4-144%. The standard deviation (SD) values for all analytes were <0.10 for both intraday and interday accuracy and precision. The selectivity, accuracy and precision of this method are satisfactory for clinical and forensic applications. The sensitive and selective method offers the opportunity for the simultaneous screening and quantification, for clinical and forensic purposes, of almost all local anesthetics available in Japan.

A study of the in vitro interaction between ethanol, and triazolam and its two metabolites using human liver microsomes.

AIM: Triazolam is widely used as an ultrashort-acting anxiolytic drug and hypnosedatives and its effect appears at very low doses. Ethanol is used as a social drug worldwide. Sometimes, toxic interactions occur following combined administration of these two drugs. In this study, we have investigated the interaction between alcohol and triazolam in vitro. METHODS: The interaction effects between alcohol and triazolam were examined by a mixed-function oxidation reaction using a human liver microsomal preparation. Triazolam and its two metabolites (alpha-hydroxytriazolam: alpha-OH triazolam, 4-hydroxytriazolam: 4-OH triazolam) were measured by HPLC/UV. RESULTS: The production of alpha-OH triazolam and 4-OH triazolam was shown to be weakly inhibited by 13-29% (p < 0.05) and 8-14%,respectively, by ethanol (20-80 mM). CONCLUSIONS: These results using a human liver microsomal preparation show that the formation of both metabolites of triazolam is weakly inhibited by ethanol. Toxic levels may be reached by simultaneous administration of ethanol and triazolam.

Life-threatening veno-occlusive disease after living-related liver transplantation.

Veno-occlusive disease (VOD) can develop in association with the administration of cytotoxic chemotherapeutic agents and irradiation. In solid-organ transplant settings, azathioprine has been implicated as a predisposing factor. VOD with fatal outcome occurred in a post liver-transplant recipient who had never been exposed to any agents that have the potential to induce VOD. At onset, the disease manifested clinically as gross ascites and progressive jaundice and was observed after clinically diagnosed acute graft rejection. The disease was confirmed by histologic examinations. Histologic studies of biopsy samples from this patient revealed that most small hepatic veins less than 300 microm in diameter were affected, exhibiting concentric intimal thickening with sparse inflammatory cells. A few of the hepatic veins exhibited active endotheliitis with occasional extension of inflammation to neighboring centrilobular areas. Despite intensified immunosuppression, the observed fibrous obliterative changes were irreversible. Although the cause of VOD in this patient is tentative, the damage to the endothelium, associated with acute rejection, is likely to be attributable. VOD deserves recognition as one of the causes for liver dysfunction and persistent ascites after liver transplantation.

Living liver donation: preoperative assessment, anatomic considerations, and long-term outcome.

BACKGROUND: A major prerequisite for living donor liver transplantation (LDLT) as an acceptable treatment modality is thoughtful consideration of the donor. However, there has been no comprehensive audit of living liver donation focusing on issues such as donor selection, anatomic surveys, and long-term outcome. METHODS: Between June 1990 and January 2002 at our institution, 160 LDLTs were performed and 177 patients were referred for LDLT. For these patients, a total of 203 potential donors were screened. The process of donor selection, safety of donor hepatectomy, and postoperative morbidity were investigated. Additionally, an anonymous questionnaire was administered to 100 donors who had undergone LDLT more than 3 years previously. RESULTS: Thirty-eight (19%) of the 203 donor candidates were excluded. Precise estimation of the hepatic anatomy was indispensable for donor safety. None of the donors showed prolonged postoperative liver dysfunction nor developed complications requiring reoperation or readmission. There was no donor mortality. The responses to the questionnaire indicated that 95% of the living donors had not felt coerced to donate and that 5% were neutral about coercion pressure. There were no severe postoperative aftereffects, but minor problems were reported by 51% of the respondents. CONCLUSIONS: Our appraisal of the perioperative and long-term postoperative course of LDLT donors revealed that although most donors are satisfied after undergoing LDLT, there is a need for strict attention to the process of donor selection and long-term postoperative follow-up. The outcome of the present series seems to confirm the safety of donor hepatectomy.

Temporary auxiliary liver transplantation from a living donor to an adult recipient with familial amyloid polyneuropathy.

A 33-year-old patient with familial amyloid polyneuropathy (FAP) underwent temporary auxiliary partial orthotopic liver transplantation (APOLT) from a living donor with a small-for-size graft. The auxiliary left lobar graft, which weighed only 230 g, was orthotopically transplanted after resection of the recipient's left lobe. The right portal vein was transected to induce compensatory hypertrophy of the left lobar graft. Posttransplant computed tomography showed atrophy of the native liver and hypertrophy of the graft, the volume of which had increased to 446 ml by postoperative day 41. The remnant native liver was removed 6 weeks after APOLT, and there were no signs of liver dysfunction during the postoperative course. Our experience with this case suggests that temporary APOLT is the treatment of choice, guaranteeing a sufficient margin of safety for both donor and recipient, in living donor liver transplants for FAP where the donor's left lobe is disproportionately small.

Maternal methamphetamine administration during pregnancy influences on fetal rat heart development. [corrected].

Methamphetamine (MAP) is one of the most abused drugs in Japan. The rate of MAP abuse by young women has recently reached more than 50 percent in adolescents. A major health concern is that these women will continue to use MAP during pregnancy. The purpose of this study was to investigate whether MAP administered to the mother during pregnancy would change the expression of alpha- and beta- myosin heavy chain (MHC) mRNA in rat neonatal hearts, as detected by quantitative RT-PCR. In addition, morphological changes in the rat neonatal ventricles were examined. Pregnant rats were injected intraperitoneally with MAP (1 mg/kg/day) starting at day 0 of gestation and ending at day 21. There was a significant increase in alpha-MHC mRNA expression in the neonatal ventricular muscle in the experimental group compared with the control at postnatal day (P) 0 and 5. alpha-MHC mRNA expression in both groups was similar after P9. beta-MHC mRNA expression was similar in both groups at P0. Postnatal beta-MHC mRNA expression decreased rapidly, but significant alteration was not detected. Neonatal rats at P0 exhibited some cardiac changes, including hypertrophy, degeneration, and disarrangement of myofibers, but these lesions disappeared by P14. We conclude that chronic maternal administration of MAP changes the alpha- and beta-MHC mRNA expression pattern in fetal and neonatal hearts, correlating with abnormal development, plasma level of hormones, and myocardial damage. At the same time, it is indicated that neonatal cardiomyocytes have reversibility.

Simultaneous determination of flunitrazepam and 7-aminoflunitrazepam in human serum by ion trap gas chromatography-tandem mass spectrometry.

A method for the determination of flunitrazepam (FNZ) and 7-aminoflunitrazepam (7-AFNZ) in human serum was developed with ion trap gas chromatography (GC)-tandem mass spectrometry. The 7-AFNZ was derivatizated with 50 microl trifluoroacetic anhydride (TFAA), 60 degrees C-20 min. EI mass spectra and tandem mass spectra of FNZ and 7-AFNZ-TFA were m/z 238, 239, 266, 286, 294, 312, 313(M(+)), m/z 350, 351, 360, 378, 379(M(+)), m/z 238, 239, 240 (precursor ion m/z 286, collision energy 1.5 V), and m/z 239, 254, 264, 336 (precursor ion m/z 351, collision energy 1.8 V), respectively. The detection limits of full scan EI mass spectrometry and tandem mass spectrometry for FNZ and 7-AFNZ in human serum were ca. 200 ng/ml, 60 ng/ml, 15 ng/ml and 1 ng/ml, respectively.

Analysis of quazepam and its metabolites in human urine by gas chromatography-mass spectrometry: application to a forensic case.

A sensitive method for the simultaneous determination of quazepam and two of its metabolites, 2-oxoquazepam and 3-hydroxy-2-oxoquazepam, in human urine was developed using gas chromatography-mass spectrometry (GC/MS) with an Rtx-5MS capillary column. The quazepam and its metabolites were extracted from human urine using a simple solid-phase extraction Oasis(®) HLB cartridge column, and the 3-hydroxy-2-oxoquazepam was derivatised using BSTFA/1%TMCS and pyridine at 60 °C for 30 min. The mass spectrometric detection of the analytes was performed in the full scan mode, m/z 60-480, and selected ion monitoring (SIM) mode, m/z 386, for quazepam; m/z 342, for 2-oxoquazepam; m/z 429, for 3-hydroxy-2-oxoquazepam-TMS; and m/z 284, for alprazolam-d5 (internal standard), by electron ionization. The calibration curves of quazepam and its metabolites in urine showed good linearity in the concentration range of 2.5-500 ng/0.2 ml of urine. The average recoveries of quazepam and its metabolites from 0.2 ml of urine containing 500 ng and 50 ng of each drug were 71-83% and 88-90%, respectively. The limits of detection of quazepam, 2-oxoquazepam and 3-hydroxy-2-quazepam in urine by the selected ion monitoring mode were 0.096-0.37 ng/ml. This method would be applicable to other forensic biological materials containing low concentrations of quazepam and its metabolites.

Simultaneous determination for oxicam non-steroidal anti-inflammatory drugs in human serum by liquid chromatography-tandem mass spectrometry.

A high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique was developed for the simultaneous determination of five non-steroidal anti-inflammatory oxicam drugs (ampiroxicam, tenoxicam, piroxicam, meloxicam and lornoxicam) in human plasma. These five oxicam drugs and isoxicam (internal standard) were extracted from human plasma with an Oasis(®) MAX cartridge column and analysed on a Unison UK-C18 column (2.0 mm × 100 mm, 3 µm) with an acetonitrile:10mM formic ammonium buffer (pH 3.0) (50:50) mobile phase at 0.20 ml/min at 37°C. The analytes were detected using a tandem mass spectrometer, equipped with an electrospray ion source (ESI). The instrument was used in multiple-reaction-monitoring (MRM) mode. The extraction yields from a 200 µl human plasma sample (containing 10 ng of each drugs) with the Oasis(®) MAX cartridge column were 93.3-102.5%. The detection limits were 0.01-6.5 ng/ml (S/N=3). Our developed method is very useful for the simultaneous determination of five oxicam (non-steroidal anti-inflammatory) drugs in human plasma by LC/MS/MS.