Determination of phloroglucinol by HPLC-MS/MS and its application to a bioequivalence study in healthy volunteers.

OBJECTIVE: The aim of this study was to compare the pharmacokinetic characteristics of phloroglucinol between an orally disintegrating tablet and an orally lyophilized tablet of phloroglucinol in healthy volunteers under fasting condition. PATIENTS AND METHODS: A rapid and simple method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the determination of phloroglucinol in human plasma. The plasma sample was prepared by liquid-liquid extraction, and paracetamol was chosen as the internal standard. Phloroglucinol and IS were separated on a C18 column with a mobile phase consisted of methanol/water (80:20 v/v) with 0.02% formic acid. HPLC-MS/MS analyses were performed on a triple- quadruple tandem mass spectrometer by monitoring protonated parent→daughter ion pairs at m/z 125.0→56.9 for phloroglucinol, and m/z 150.2→107.0 for paracetamol (IS). The method was the high sensitivity with a lower limit of quantification (LLOQ) of 1.976 ng/mL. RESULTS: Drug and IS were detected by HPLC/MS/MS with negative electrospray ionization (ESI). Accuracy and precision for the assay were determined by calculating the intra- and inter-batch variation of quality control (QC) samples at three concentration levels. The relative standard deviation (RSD) was less than 15.0%. The detection and quantitation of drug and IS within 4.5 min make this method suitable for high-throughput analyses. In this study, the Cmax of phloroglucinol were calculated to 515.6 ± 134.4 ng/mL and 536.0 ± 144.8 ng/mL for the test drug and the reference drug, respectively. The AUC0-t values were 459.5 ± 81.03 ng·mL-1·h and 491.8 ± 95.17 ng·mL-1·h for the test drug and the reference drug; 24 subjects completed the study, respectively. The geometric mean ratio (GMR) and the 90% confidence intervals (CIs) of Cmax and AUC0-t of phloroglucinol were 97.1 (90.2-103.9) and 93.8 (88.7-99.2), respectively. CONCLUSIONS: The method was employed for the first time during pharmacokinetic studies of phloroglucinol in human plasma following a single dose of phloroglucinol 160 mg tablets. There was no significant difference in pharmacokinetic profiles between the two treatments.

Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010.

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n = 517) exhibited MICs of 2 µg/ml and 0.3 % (n = 6) demonstrated intermediate susceptibility (MICs of 4 µg/ml). Nearly all isolates (≥ 99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC90 values were 2 µg/ml for ceftobiprole and 1 µg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12 and 4 µg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 µg/ml, the MIC90 values were 2 µg/ml for teicoplanin, 0.5 µg/ml for daptomycin, and 0.5 µg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 µg/ml (2, 0.06, and 0.12 µg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n = 6), teicoplanin (n = 1), daptomycin (n = 2), or tigecycline (n = 1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 µg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.

Pseudoaneurysm of the internal iliac artery resulting in massive per-rectal bleeding.

Rectal bleeding is a common reason for presentation to hospital, with large bleeds most commonly caused by diverticular disease and angiodysplasia. Here we present an unusual aetiology of massive per-rectal bleeding attributable to pseudoaneurysm of the internal iliac artery leading to an arterial fistula to the distal large bowel. It is hoped the case will serve as a reminder that rectal bleeding can have a less common aetiology.

The development of a rapid prototyping prosthetic socket coated with a resin layer for transtibial amputees.

This article proposes a type of transtibial socket composed of an inner layer fabricated by a rapid prototyping (RP) machine and an outer layer coated with unsaturated polyester resin. This work integrates contemporary technologies including a handheld scanner and CAD systems, to design a thin primary socket shape and then manufactures the socket using a fused deposition-modeling machine. To prevent breakage caused by the layer-based forming process and to reinforce flexural strength, the current research coats the preliminary RP socket with a layer of unsaturated polyester resin. After shaping the proximal brim of the resin-reinforced RP socket to match the specific stump, this study assembles and aligns a shank and a prosthetic foot to form a prosthesis set. After completing a trial safety walk wearing the prosthesis, which is satisfactory to the amputee and a registered prosthetist, this research measures interface pressures between the stump and the resin-reinforced RP socket. Experiment results demonstrate that the resin-reinforced RP socket is applicable for transtibial amputees. In addition to strengthening the FDM socket and producing consistent socket fit, this study also demonstrates a feasible procedure that employs current technologies to design and manufacture transtibial sockets without plaster moulds.

Elective laparoscopic surgical management of recurrent and complicated sigmoid diverticulitis.

BACKGROUND: To review the results of elective laparoscopic anterior resection (LAR) for recurrent and complicated sigmoid diverticulitis, and determine the factors associated with surgical complications. METHODS: Data on patients who had had elective surgery for recurrent and complicated sigmoid diverticulitis were extracted from a prospective computerized database. RESULTS: Review of the database revealed 62 consecutive patients who had undergone LAR. These patients were initially compared with 20 patients who had undergone elective open anterior resection (OAR). There were no significant differences between the groups in relation to age, sex, indication for surgery, Hinchey stage of perforation, extent of adhesions or comorbidities. The intraoperative time for LAR was significantly shorter (mean+/-SEM 110.87+/-4.8 min vs. OAR 134.35+/-8.4; p=0.032) and blood loss was less (88+/-18 ml vs. OAR 134+/-24 ml; p=0.003). Postoperative passage of flatus occurred earlier after LAR (p<0.003). Hospital stay was shorter after LAR (p<0.001). Complications occurred in nine patients (15%) after LAR and in six patients (30%) after OAR (p=NS). Among the LAR patients the risk of complications was higher in those with preexisting comorbidities (p=0.037). Time to postoperative passage of flatus correlated positively with age (p=0.004). CONCLUSIONS: Elective LAR for recurrent and complicated sigmoid diverticulitis could be performed safely and expediently. Bowel function recovered later in older patients. The risk of medical complications was related to preexisting comorbidities.

The role of Schwann cell differentiation in perineural invasion of adenoid cystic and mucoepidermoid carcinoma of the salivary glands.

Twenty cases of adenoid cystic carcinoma (ACC) and 18 cases of mucoepidermoid carcinoma (MEC), were examined for expression of the Schwann cell markers S100 protein and glial fibrillary acidic protein (GFAP) by immunohistochemical staining. The relationship between expression of S100 and GFAP and the occurrence of perineural invasion was assessed. Ultrastructural localization of S100 and GFAP was examined by immunoelectron microscopy, and the co-expression of S100 and muscle actin by double fluorescence immunostain. Perineural invasion was found in 11 ACCs (55%) and 0 MECs (0%). S100 and GFAP were expressed in most of the ACCs but none of the MECs; the difference in the rate of perineural invasion and expression of S100 and GFAP was significant between ACC and MEC (P<0.001). There was a correlation between the expression of S100 and GFAP and perineural invasion in salivary malignancy (P<0.001). The ultrastructures of S100- and GFAP-positive cells were consistent with the characteristics of myoepithelial cells. Double fluorescence immunostain also showed that S100 and muscle actin were expressed in the same type of ACC cells. These results indicate that Schwann cell differentiation correlates with perineural invasion in salivary malignancy, and occurs in modified myoepithelial cells of ACC.

Crystallization and preliminary X-ray analysis of endopolygalacturonase SE1 from Trichosporon penicillatum.

Endopolygalacturonase SE1 from Trichosporon penicillatum has been crystallized by the hanging-drop method of vapour diffusion using ammonium sulfate as a precipitant. The crystals belong to the hexagonal space group P6(1) or P6(5), with unit-cell parameters a = b = 135.0, c = 70.7 A, gamma = 120 degrees. The calculated V(M) based on one molecule per asymmetric unit is 3.09 A(3) Da(-1). A native data set from a crystal has been collected to 2.0 A resolution on a Cu Kalpha rotating-anode X-ray source.

Iodixanol and ioxaglate in adult aortography and peripheral arteriography: a phase III clinical trial.

RATIONALE AND OBJECTIVES: This study compared the safety and efficacy of iodixanol with those of ioxaglate in adult patients undergoing aortography or peripheral arteriography. METHODS: Forty-six patients were enrolled in this controlled, randomized, double-blind, two-center study. The patients were monitored for adverse events, injection-related discomfort, and trends in laboratory data or vital signs. Diagnostic efficacy was assessed by the quality of contrast enhancement. RESULTS: All procedures were diagnostic, with no significant difference in quality of visualization (p = .205). No significant difference was seen in the number of patients experiencing mild or moderate adverse effects (p = .106). Patients receiving ioxaglate reported a significantly greater incidence of injection-related pain (p = .025). CONCLUSION: The results of this study support the conclusion that iodixanol at 320 mg I/kg is safe and effective for adult aortography and peripheral arteriography and causes significantly less injection-related pain than ioxaglate.

Angiographic selection criteria for living related liver transplant donors.

OBJECTIVE: The purpose of this study is to better define arteriographic selection criteria for living related liver transplantation (LRLT) based on literature review, technical and theoretical considerations, and correlation of patterns of variation in hepatic artery anatomy with recipient and donor outcomes. MATERIALS AND METHODS: Visceral angiograms of 92 consecutive living related liver transplant donors were retrospectively reviewed by two radiologists and one transplant surgeon. Arterial configurations were categorized. Recipient and donor outcomes were determined by a review of transplant surgery and radiology records. RESULTS: Anomalous hepatic artery anatomy was identified in 67% of potential donors. A left hepatic artery (LHA) with a diameter of less than 2 mm was identified in 1%, and with a diameter of 2-3 mm, in 5%. A dual LHA supply to the left lateral segment was identified in 11%. Two subtypes were defined. Bifurcation of the LHA into branches entering segment II and segment III less than 1 cm from the LHA origin was present in 8%. A replaced LHA from the left gastric artery (17%) and complex, aberrant branching of the LHA (4%) were identified. Vital LHA supply to tissue other than the left lateral segment was present in 21%, including the cystic artery as a branch of the LHA (4%), significant supply of the right lobe from the LHA (5%), and large branches from the LHA entering segment IV (13%). All three donors with significant supply of the right lobe from the transplanted LHA had complications. CONCLUSION: Absolute exclusionary criteria for LRLT are an LHA diameter of less than 2 mm, dual arterial supply to liver segments II and III, indeterminate arterial anatomy, preexisting vascular disease in donor liver, and a significant LHA supply to the right lobe. Relative exclusionary criteria are an LHA diameter of 2-3 mm, early bifurcation of the LHA, and arterial supply of segment 4 exclusively from the LHA.

A case-control study of oral cancer in Changhua County, Taiwan.

Forty oral cancer patients identified consecutively in Changhua Christian Hospital between 1990 and 1992 were compared with 160 population-based controls, matched for sex, age, area of residence, and educational background. Betel quid chewing was positively associated with the risk of oral cancer with adjusted odds ratio of 58.4 (95% CI: 7.6-447.6). The greater the number of years of chewing betel quid, the higher the risk of oral cancer; the adjusted odds rations were 12.9, 93.7 and 397.5 for < 21, 21-40, and > 40 years of betel chewing as compared with the non-users. The risk also increased with the quantity chewed per day; the odds ratios for those chewing < 10, 10-20 and > 20 quids/day were 26.4, 51.2 and 275.6, respectively. These odds ratio estimates were all statistically significantly different from the null value of unity.

Comparative efficacy and complications of vena caval filters.

PURPOSE: A variety of vena caval filters (VCFs) are available for usage. The choice of filter type depends on physician preference and certain patient variables. An evaluation of the different VCFs used in our institution was done to compare their efficacy and complication rates. METHODS: The medical records of all patients who underwent insertion of a VCF from January 1987 to June 1993 at the University of Iowa Hospitals & Clinics and the affiliated Veterans Administration Medical Center were reviewed. One hundred ninety-nine VCFs were placed in 196 patients (123 males, 73 females), with a mean age of 61 years (range 13 to 87 years). Thirty-five (18%) VCFs (30 stainless steel Greenfield filters [SGFs] and five titanium Greenfield filters with modified hook [TGF-MHs]) were inserted in the operating room via an open technique. The remaining 164 VCFs (82%) were inserted in the radiology suite by a percutaneous technique (38 SGF, 23 TGF-MH, 51 Vena Tech filters [VTFs], 48 Bird's nest filters [BNFs] and 4 Simon Nitinol filters). Thromboembolic risk factors in these 196 patients included malignancy (99), trauma (21), recent surgery (27), cerebrovascular accident with paralysis (6), and miscellaneous conditions (43). Indications for VCF placement included a contraindication to anticoagulation (92), complication of anticoagulation (44), failure of anticoagulation (26), prophylaxis (31), adjunct to pulmonary embolectomy (1), noncompliance (1), hemodynamically unstable patient (1), and prior VCF complication (3). Mean follow-up of the patients was 12 months (range 0 to 87 months). Because there were only four Simon Nitinol filters inserted during the study period, they were excluded from further analysis. RESULTS: A comparative analysis revealed that there was a significantly higher incidence of symptomatic IVC thrombosis with the use of the BNF (n = 7) (14.6%) versus the SGF (n = 0) (0%), TGF-MH (n = 1) (3.6%), or VTF (n = 2) (4%) (p < 0.05 by chi-squared testing). The VCF-related mortality rate was also higher with the BNF (n = 5) (10.9%) versus the SGF (n = 1) (1.5%), TGF-MH (n = 1) (3.6%), or VTF (n = 0) (0%) (p < 0.05 by chi-squared testing). However there was no significant difference in the occurrence of clinically apparent recurrent pulmonary embolism during follow-up between the four different filter types (2 [4.2%] BNF, 3 [4.4%] SGF, 1 [3.6%] TGF-MH, and 1 [2%] VTF). CONCLUSION: These data indicate that the use of the BNF was associated with increased morbidity and mortality rates compared with the use of the SGF, TGF-MH, and VTF filters.

Transcatheter embolization of an internal mammary artery bypass graft sidebranch causing coronary steal syndrome.

We describe a 66-yr-old man with angina after internal mammary artery-coronary bypass grafting due to coronary artery steal by a sidebranch of the mammary artery. Myocardial ischemia was successfully treated by transcatheter embolization of the sidebranch.

Prevalence and characteristics of areca nut chewers among junior high school students in Changhua county, Taiwan.

Some studies indicate that betel quid and its ingredients chewing can produce cell mutagenicity and tumorigenicity. In Taiwan studies, betel quid chewing is the main cause of submucous fibrosis and oral cancer. Understanding the distribution and characteristics of the areca nut chewing population is one of the first steps in the effort to prevent these oral diseases. A stratified cluster random sample of 2442 junior high school students in Changhua county, Taiwan, were surveyed for the habit of areca nut chewing. Significantly more male students chewed areca nut than female students (9.2% vs 0.9%). The proportion of students who were chewing areca nuts increased with increasing (seventh to ninth) grades. Areca nut was used by junior high school students at a higher rate in village (rural) areas as compared to town (semi-urban) and city (urban) areas (6.4%, 3.7% and 3.0%, respectively). More students in the ordinary achievement classes were chewing areca nuts than those in the high achievement classes (8.4% vs 1.6%). Areca nut chewing students tended to have users in their families. Cigarette smoking and alcohol drinking were positively associated with areca nut chewing. More than half (53.6%) of the areca nut chewing students first experimented with this habit with a family member, most often the father or grandfather.

Strategies for blood screening for the hepatitis C virus and for the human immunodeficiency virus in high risk groups.

For many infectious agents, seroprevalence rate is low but has serious consequences and must therefore be kept out of donated blood supplies. However, screening to ensure the safety of blood supplies has an associated very high cost. For example, in blood banks, detection of all the harmful items in a large number of samples is an expensive and tedious process. The laboratory and statistical approaches to obtain significant savings by the pooling method were discussed from 1943, recently, there have been further discussions of pooling sera as a means to determining the HIV seroprevalence rate in the general population or the weed out all HIV-positive individuals in blood screening. Here we describe a simple mathematical method to weed out all HIV, and HCV seropositive units. The method is designed to maximize possible savings. Two examples illustrate the application of this method in determining the number to be pooled in each stage, and the resulting savings. When the prevalence rate is lower than 2 percent. our method offers savings of over 80 percent.

Vena Tech vena cava filter: experience and early follow-up.

Vena caval filters, such as the Vena Tech filter, that employ low-profile introducer systems have provided physicians with a variety of options for percutaneous placement. From April 1989 to April 1990, 81 patients underwent percutaneous placement of the Vena Tech filter at the authors' institution. Follow-up has been obtained to evaluate the filter with regard to the prevention of pulmonary embolism, the maintenance of caval patency, and mechanical stability. Two cases of pulmonary embolism have been seen following filter placement. Three cases of caval thrombosis have occurred, with recanalization of the cava seen in two of these cases. There have been one broken filter and one case of incomplete filter opening. Limited filter tilting and migration have occurred, though in no case has filter tilt or migration been clinically significant. This experience with the Vena Tech filter suggests that it is safe and effective for the prevention of pulmonary embolism.

[Effects of stimulation of locus coeruleus on cardiac contractility and renal nerve activity].

Experiments were performed on 64 cats anesthetized with chloralose-urethane, paralyzed and artificially ventilated. Electrical stimulation of locus coeruleus (LC) elicited increases in BP, HR, LVSP, dP/dt max and RNA. Buffer nerve section had no effect on the increase of these parameters, but could prolong the time of rise of BP and recovery phases. Injection of L-glutamate into LC, on the other hand, could decrease BP, HR, LVSP and dP/dt max. Intra-LC injection of kainic acid could also decrease BP. When the LC neurons showed degeneration or depolarization block after kainic acid injection, electrical stimulation of the LC could still elicit marked pressor response. The results suggest that the pressor response induced by electrical stimulation of LC might be mediated by the fibers passing through LC, while activation of LC neurons themselves would result in the depressor response.

A new technique for direct percutaneous jejunostomy tube placement.

We describe a case in which we employed a new method of using intraluminal balloon support for direct percutaneous placement of a jejunostomy tube. Standard interventional radiologic techniques and readily available equipment and materials were used.