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1.
Dis Esophagus ; 30(8): 1-6, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28575244

ABSTRACT

Gastric pull-up is a common procedure to reconstruct the continuity of the upper digestive tract after esophageal resection. However, this technique sometimes causes postoperative anastomotic leakage or stricture, resulting from insufficient blood flow at the distal end. To overcome this problem, additional microvascular venous anastomoses were performed. The purpose of this study was to compare the outcomes of post-surgical anastomotic leakage and stricture in patients with and without additional microvascular venous superdrainage after cervical esophageal and hypopharyngeal resection and gastric tube reconstruction. A total of 29 consecutive patients with esophageal or hypopharyngeal cancer who underwent total esophagectomy and hypopharyngectomy with gastric tube reconstruction in the National Organization Nagasaki Medical Center between April 2014 and May 2016 were analyzed in this study. Of these patients, 20 underwent additional venous anastomoses (superdrainage group), and 9 did not undergo additional procedures (standard group). We compared the frequency of post-surgical stricture and leakage in the two groups retrospectively. Three of nine patients (33.3%) developed postoperative leakage in the standard group, and 1 of 20 (5.0%) did so in the superdrainage group. Six of nine patients (66.7%) showed postoperative anastomotic stricture in the standard group, but none did so in the superdrainage group. Patients who did not undergo additional venous superdrainage were significantly more likely to develop postsurgical leakage (P < 0.05, Chi-square test) and anastomotic stricture (P < 0.001, Chi-square test). Our study revealed that only additional venous anastomoses could reduce the incidence of postoperative anastomotic leakage and stricture. This procedure is of merit to perform after total esophagectomy and hypopharyngectomy with gastric tube reconstruction.


Subject(s)
Anastomotic Leak/prevention & control , Drainage/methods , Esophageal Stenosis/prevention & control , Esophagoplasty/methods , Esophagus/surgery , Microvessels/surgery , Aged , Aged, 80 and over , Anastomosis, Surgical/methods , Anastomotic Leak/etiology , Esophageal Stenosis/etiology , Esophagectomy/adverse effects , Esophagus/blood supply , Female , Humans , Hypopharynx/surgery , Male , Middle Aged , Neck/surgery , Retrospective Studies , Stomach/blood supply , Stomach/surgery , Treatment Outcome
2.
Rev Sci Instrum ; 87(7): 076103, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27475610

ABSTRACT

A novel diamond anvil cell suitable for electrical transport measurements under high pressure has been developed. A boron-doped metallic diamond film was deposited as an electrode on a nano-polycrystalline diamond anvil using a microwave plasma-assisted chemical vapor deposition technique combined with electron beam lithography. The maximum pressure that can be achieved by this assembly is above 30 GPa. We report electrical transport measurements of Pb up to 8 GPa. The boron-doped metallic diamond electrodes showed no signs of degradation after repeated compression.

3.
AJNR Am J Neuroradiol ; 35(8): 1509-14, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24699091

ABSTRACT

BACKGROUND AND PURPOSE: Diffusion kurtosis is a statistical measure for quantifying the deviation of the water diffusion profile from a Gaussian distribution. The current study evaluated the time course of diffusion kurtosis in patients with cerebral infarctions, including perforator, white matter, cortical, and watershed infarctions. MATERIALS AND METHODS: Subjects were 31 patients, representing 52 observations of lesions. The duration between the onset and imaging ranged from 3 hours to 122 days. Lesions were categorized into 4 groups listed above. Diffusion kurtosis images were acquired with b-values of 0, 1000, and 2000 s/mm(2) applied in 30 directions; variables including DWI signal, ADC, fractional anisotropy, radial diffusivity, axial diffusivity, radial kurtosis, and axial kurtosis, were obtained. The time courses of the relative values (lesion versus contralateral) for these variables were evaluated, and the pseudonormalization period was calculated. RESULTS: Diffusion kurtosis was highest immediately after the onset of infarction. Trend curves showed that kurtosis decreased with time after onset. Pseudonormalization for radial/axial kurtosis occurred at 13.2/59.9 days for perforator infarctions, 33.1/40.6 days for white matter infarctions, 34.8/35.9 days for cortical infarctions, and 34.1/28.2 days after watershed infarctions. For perforator infarctions, pseudonormalization occurred in the following order: radial kurtosis, ADC, axial kurtosis, and DWI. CONCLUSIONS: Diffusion kurtosis variables in lesions increased early after infarction and decreased with time. Information provided by diffusion kurtosis imaging, including axial and radial kurtosis, seems helpful in conducting a detailed evaluation of the age of infarction, in combination with T2WI, DWI, and ADC.


Subject(s)
Cerebral Infarction/pathology , Diffusion Magnetic Resonance Imaging/methods , White Matter/pathology , Adult , Aged , Anisotropy , Female , Humans , Male , Middle Aged
4.
J Thromb Haemost ; 12(4): 505-14, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24476338

ABSTRACT

BACKGROUND: Microthrombosis and reactive inflammation contribute to neuronal injury after subarachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions. OBJECTIVE: To investigate the effect of ADAMTS-13 in experimental SAH. METHODS: A total of 100 male C57/BL6 mice were randomly assigned to four groups: sham (n = 15), SAH (n = 27), vehicle (n = 25), and ADAMTS-13 (n = 23; 100 µL per 10 g of body weight of 100 µg of ADAMTS-13 per 1 mL of 0.9% NaCl; 20 min after SAH). Neurologic performance was assessed on days 1 and 2 after SAH. Animals were killed on day 2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also compared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2 h after SAH. RESULTS: Systemic administration of ADAMTS-13 achieved significant amelioration of microthrombosis and improvement in neurologic performance. ADAMTS-13 reduced the amount of apoptotic and degenerative neurons. A tendency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vasospasm. The degree of systemic inflammation was not changed by ADAMTS-13 administration. ADAMTS-13 neither increased the amount of subarachnoid blood nor prolonged the bleeding time. CONCLUSIONS: ADAMTS-13 may reduce neuronal injury after SAH by reducing microthrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.


Subject(s)
ADAM Proteins/therapeutic use , Intracranial Thrombosis/therapy , Neurons/pathology , Subarachnoid Hemorrhage/therapy , ADAMTS13 Protein , Animals , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Hemorrhage , Humans , Inflammation , Intracranial Thrombosis/blood , Male , Mice , Mice, Inbred C57BL , Neurons/metabolism , Recombinant Proteins/therapeutic use , Subarachnoid Hemorrhage/blood , Time Factors , von Willebrand Factor/metabolism
5.
Sci Technol Adv Mater ; 15(5): 055007, 2014 Oct.
Article in English | MEDLINE | ID: mdl-27877719

ABSTRACT

The transport and magnetic properties of the tetragonal Fe[Formula: see text]S were investigated using magnetoresistivity and magnetization within [Formula: see text] K, [Formula: see text] 70 kOe and [Formula: see text] 3.0 GPa. In addition, room-temperature x-ray diffraction and photoelectron spectroscopy were also applied. In contrast to previously reported nonmetallic character, Fe[Formula: see text]S is intrinsically metallic but due to a presence of a weak localization such metallic character is not exhibited below room temperature. An applied pressure reduces strongly this additional resistive contribution and as such enhances the temperature range of the metallic character which, for ∼3 GPa, is evident down to 75 K. The absence of superconductivity as well as the mechanism behind the weak localization will be discussed.

6.
Pharmazie ; 68(6): 406-13, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23875246

ABSTRACT

We recently developed a prodrug (AS1932804-00, CMP) of the novel FVIIa inhibitor AS1924269-00, which possesses a carbamate amidine backbone. In addition, we developed another type of prodrug (AS1927819-00, OXP) with an oxime amidine backbone. In this study, we investigated the efficiency of conversion of these novel FVIIa prodrugs to their active forms by evaluating the production of the active form in vitro by using microsomes, mitochondria, and cryopreserved hepatocytes, and compared it with the in vivo conversion mechanisms of the prodrugs (oxime amidine vs. carbamate amidine). We observed that OXP and CMP showed improved oral absorption, and the efficiency of conversion of CMP to the active form was higher than that of OXP. The in vivo rate of conversion of OXP to its active form was low in rats, and compared to liver microsomes and mitochondria, cryopreserved hepatocytes supplemented with serum and coenzymes were an appropriate metabolic test tool. On the other hand, the efficiency of conversion of CMP to its active from could be appropriately evaluated using small intestinal microsomes. The development of a prodrug can be optimized when information about the stability of carboxylic acid esters in the presence of serum esterases, membrane permeability of intermediate forms, and differential tissue specificity to metabolic activities for carbamate and oxime backbones of amidine can be obtained.


Subject(s)
Anticoagulants/pharmacokinetics , Factor VIIa/antagonists & inhibitors , Phenoxyacetates/pharmacokinetics , Animals , Azetidines/pharmacokinetics , Benzylamines/pharmacokinetics , Biotransformation , Hepatocytes/metabolism , In Vitro Techniques , Intestinal Mucosa/metabolism , Kinetics , Microsomes, Liver/metabolism , Mitochondria, Liver/metabolism , NAD/metabolism , NADP/metabolism , Prodrugs/metabolism , Rats
7.
Pharmazie ; 68(5): 349-54, 2013 May.
Article in English | MEDLINE | ID: mdl-23802432

ABSTRACT

AS1924269-00 is a promising orally applicable anticoagulant that inhibits FVIIa but has very low oral absorption. Therefore, in this study, we aimed to develop a prodrug of AS1924269-00, which possesses a carbamate-added amidine functional group, with high membrane permeability. We investigated the pharmacokinetics of the carbamate-type prodrug of AS1924269-00 in rats. The Caco-2 cell monolayer was used as an in vitro model and in parallel an artificial membrane permeability assay (PAMPA) was performed to examine the transport mechanisms of the prodrug. The bioavailability of the active form was determined to be only 0.3% in rats, but the oral absorption of the prodrug was markedly improved, and its bioavailability was 36%. Our in vivo result was consistent with the finding that compared to AS1924269-00, the prodrug showed favorable permeability in Caco-2 cells and PAMPA. We introduced carbamate into the amidine functional group of the FVIIa inhibitor, which possesses the amidine backbone, and converted it to a prodrug using carboxylic acid ethyl ester. This novel prodrug had favorable absorption and membrane permeability in vivo and in vitro. Thus, we suggest a clinical application of the carbamate-added amidine prodrug of the FVIIa inhibitor.


Subject(s)
Amidines/pharmacokinetics , Anticoagulants/pharmacokinetics , Factor VIIa/antagonists & inhibitors , Phenoxyacetates/pharmacokinetics , Amidines/administration & dosage , Animals , Anticoagulants/administration & dosage , Caco-2 Cells , Chromatography, High Pressure Liquid , Half-Life , Humans , Indicators and Reagents , Male , Mass Spectrometry , Membranes, Artificial , Permeability , Phenoxyacetates/administration & dosage , Rats , Rats, Sprague-Dawley
8.
Minerva Anestesiol ; 76(10): 868-71, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20935624

ABSTRACT

Central venous catheter (CVC)-induced hydrothorax is a delayed complication after the placement of an indwelling subclavian or internal jugular central venous catheter. The catheter tips may cause long-lasting mechanical damages that lead to a slow erosion of the wall of the superior vena cava (SVC), thereby resulting in hydrothorax. The damage may stem from the catheter tips being positioned inappropriately or from the relocation of the catheter tip that was initially ideally positioned. We describe an 80-year-old woman with CVC-induced hydrothorax. She presented with spinal subdural hematoma and preoperatively underwent a multiple-lumen CVC insertion through her left subclavian vein. Her recovery course was uneventful after surgical hematoma removal and spinal cord decompression. However, thirty hours after the CVC placement, the patient began to suffer from an increasing dyspnea. The chest X-ray showed right-sided, massive pleural effusion and a widened mediastinum, requiring the removal of the CVC and the drainage of the pleural fluid. After these procedures, the respiratory status improved rapidly. The present case report suggests that the complication of a hydrothorax may occur after a patient's position changes, and it usually occurs in cases where the catheter tip was initially placed in the ideal position. Operators responsible for CVC placement have to be aware of this delayed complication and have the catheter tips remain in a consistently appropriate position.


Subject(s)
Catheterization, Central Venous/adverse effects , Hydrothorax/etiology , Postoperative Complications/etiology , Vena Cava, Superior/injuries , Aged, 80 and over , Device Removal , Diagnostic Errors , Drainage , Dyspnea/etiology , Female , Heart Failure/diagnosis , Hematoma, Subdural, Spinal/surgery , Humans , Hydrothorax/diagnosis , Hydrothorax/physiopathology , Hydrothorax/surgery , Pleural Effusion/etiology , Pleural Effusion/surgery , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Postoperative Complications/surgery , Posture , Preoperative Care , Subclavian Vein , Wounds, Penetrating/etiology
10.
J Orthop Surg (Hong Kong) ; 17(1): 36-41, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19398791

ABSTRACT

PURPOSE: To report mid-term results of total hip arthroplasty (THA) using the Opti-Fix Plus Hip System (Opti-Fix Hip), and to assess the correlations between peri-implant bone changes and the distal medullary occupancy rate. METHODS: 11 men (13 hips) and 53 women (58 hips) aged 24 to 87 (mean, 61) years underwent THA using the Opti-Fix Hip, with a modular stem and a distal sleeve, and were followed up for a mean of 6.5 (range, 4.8-9.6) years. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) hip score. Implant stability, bone changes around the implant, and the occupancy rate of the stem in the medullary space were examined radiologically. Bone changes around the implant were assessed based on the radiological evidence of a pedestal, osteolysis, stress shielding, and radiolucent lines. RESULTS: The mean JOA score increased significantly after surgery and was maintained at the latest follow-up. Around the acetabular and femoral components respectively, 38 and 58 hips had radiolucent lines, whereas one and 54 hips developed osteolysis. A pedestal appeared in 21 hips and grade-III or higher stress shielding in 30 hips. Two hips showed loosening of the acetabular components, but none in the femoral components. Osteolysis around the stem was frequently observed in hips with poor distal medullary occupancy. CONCLUSION: Clinical and radiological outcomes of the Opti-Fix Hip were favourable. The low incidence of osteolysis in the distal stem suggests that the proximal circumferential porous coating was effective. Minor osteolysis around the proximal stem was frequently observed, indicating early excessive wear of the polyethylene liner. Its high distal medullary occupancy rate could inhibit stem micromotion and aseptic loosening.


Subject(s)
Arthroplasty, Replacement, Hip/instrumentation , Femur Head Necrosis/surgery , Hip Prosthesis , Osteoarthritis, Hip/surgery , Osteolysis/epidemiology , Adult , Aged , Aged, 80 and over , Equipment Failure Analysis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Osteolysis/diagnostic imaging , Prosthesis Design , Radiography , Range of Motion, Articular , Treatment Outcome , Young Adult
11.
J. venom. anim. toxins incl. trop. dis ; 15(1): 168-178, 2009. ilus
Article in English | LILACS, VETINDEX | ID: lil-508239

ABSTRACT

Administration of antivenom is currently the standard treatment for snake envenomation. However, it can sometimes cause anaphylactic reactions including urticaria, bronchospasm and hypotension. Furthermore, it may also provoke life-threatening complications, even though the mortality rate is less than 1 percent. In this study, we present a new treatment - immediate radical fang mark ablation - that was successfully performed on five victims of Japanese viper bites without antivenom use. In these five victims of venomous snakebites, surgical debridement was immediately performed. Two patients received a free-skin graft to resurface their wounds while three of them healed conservatively (i.e. by ointment treatment without surgery). After treatment, all patients could return to work. Immediate radical ablation is a recommended procedure that can reduce the amount of venom in tissues, which consequently decreases inflammatory reactions and reduces the necessity for antivenom.(AU)


Subject(s)
Animals , Snake Bites , Snakes , Antivenins , Ablation Techniques/methods
12.
Acta Neurochir Suppl ; 103: 29-36, 2008.
Article in English | MEDLINE | ID: mdl-18496942

ABSTRACT

BACKGROUND: The thalamic cavernous angioma (CA) represents a neurosurgical challenge because of the critical neurologic functions of the thalamus and its surrounding structures and of their deep location inside the brain. Although the natural history of the thalamic CA remains undefined, several studies suggest the poor outcome of those patients especially if the symptomatic thalamic CA is treated conservatively. We describe the advantage of the paraculminar supracerebellar approach to the lesions in the brainstem. OBJECTIVE: We studied the usefulness and the safety of the paraculminar supracerebellar infratentorial transtentorial approach for the patients with thalamic CA. METHODS: One hundred and ninety two consecutive patients with CA were treated at the Department of Neurosurgery in the Zurich University Hospital between 1993 and 2003. Among these patients, we analyzed six patients (four female, mean age 43) with thalamic CA who underwent surgical removal with the paraculminar supracerebellar transtentorial approach. We retrospectively reviewed their medical charts, the neuroradiological images, and the operative notes/video records. RESULTS: Four patients of the six presented with thalamic hemorrhage. CA existed in the left thalamus in four patients and in the right in two. Preoperative symptoms included sensorimotor disturbance (three cases), double vision (three cases), Parinaud syndrome (one case), and thalamic pain (one case). All patients had the thalamic CA completely removed without any postoperative deterioration. CONCLUSIONS: This study suggests that for the removal of thalamic cavernous angioma the paraculminar supracerebellar infratentorial transtentorial approach provides the spacious surgical field with reduced risks of damaging and sacrificing surrounding vascular and neuronal system. This approach could proffer one of the best and safest surgical routes for the radical removal of thalamic cavernous angioma.


Subject(s)
Brain Neoplasms/surgery , Hemangioma, Cavernous/surgery , Neurosurgical Procedures/methods , Thalamus/surgery , Adult , Brain Neoplasms/pathology , Cavernous Sinus/pathology , Cavernous Sinus/surgery , Female , Hemangioma, Cavernous/pathology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neuronavigation/methods , Retrospective Studies , Thalamus/pathology , Tomography, X-Ray Computed/methods , Treatment Outcome
13.
Cell Death Differ ; 15(6): 1073-83, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18259196

ABSTRACT

Mitochondrial proteins such as cytochrome c, Smac/DIABLO and Omi/HtrA2 play important roles in the cell death pathways of mammalian cells. In Drosophila, the role of mitochondria in cell death is less clear. Here, we report the identification and characterization of the Drosophila ortholog of human Omi/HtrA2. We show that Drosophila Omi/HtrA2 is imported into the mitochondria where it undergoes proteolytic maturation to yield two isoforms, dOmi-L and dOmi-S. dOmi-L contains a canonical N-terminal IAP-binding motif (AVVS), whereas dOmi-S contains a distinct N-terminal motif (SKMT). DIAP1 was able to bind to both isoforms via its BIR1 and BIR2 domains. This resulted in cleavage of the linker region of DIAP1 between the BIR1 and BIR2 domains and further degradation of the BIR1 domain by the proteolytic activity of dOmi. The binding of DIAP1 to dOmi also resulted in DIAP1-mediated polyubiquitination of dOmi, suggesting that DIAP1 could target dOmi for proteasomal degradation. Consistent with this, expression of DIAP1 in Drosophila eye discs protected them from dOmi-induced eye ablation, indicating that DIAP1 plays an important role in protecting cells from the potentially lethal effects of dOmi. The ability of IAPs to bind to and ubiquitinate mitochondrial proteins such as dOmi may be a key conserved function to counterbalance the lethal effects of these proteins if accidentally released into the cytosol.


Subject(s)
Apoptosis , Drosophila Proteins/metabolism , Drosophila/enzymology , Inhibitor of Apoptosis Proteins/metabolism , Mitochondrial Proteins/metabolism , Serine Endopeptidases/metabolism , Amino Acid Motifs , Animals , Caspases/metabolism , Cytosol/enzymology , Drosophila/cytology , Drosophila/growth & development , Drosophila Proteins/antagonists & inhibitors , Drosophila Proteins/chemistry , Eye/cytology , Eye/enzymology , Eye/growth & development , High-Temperature Requirement A Serine Peptidase 2 , Mitochondrial Proteins/analysis , Mitochondrial Proteins/antagonists & inhibitors , Mitochondrial Proteins/chemistry , Protein Isoforms/chemistry , Protein Isoforms/metabolism , Serine Endopeptidases/chemistry , Ubiquitination
14.
Br J Ophthalmol ; 92(2): 186-90, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18227200

ABSTRACT

AIMS: To investigate the influence of age, disc size and axial length on the retinal nerve fibre layer (RNFL) thickness measurements of Heidelberg Retina Tomograph (HRT) and optical coherence tomography (OCT). METHODS: A total of 162 eyes of 162 Japanese normal subjects aged between 20 and 83 were enrolled in this study. The disc area and mean RNFL thickness were measured with HRT. The disc area was also measured using the fast optic nerve scan protocol, and the average RNFL thickness was measured using the fast RNFL thickness scan mode with Stratus OCT. The correlations of age, disc area and axial length with RNFL thickness measured with HRT and OCT were analysed. The associations between axial length and disc area measured with HRT and OCT were also calculated. RESULTS: RNFL thickness measured with the two instruments decreased with age. There was a significantly negative correlation between the mean RNFL thickness and disc area measured with HRT. The RNFL thickness measured with OCT correlated positively with the disc area measured with OCT, but not with the disc area measured with HRT. Both RNFL thickness and disc area measured with OCT were inversely correlated with axial length, whereas the two parameters measured with HRT had no association with axial length. CONCLUSION: In addition to the effect of ageing, the disc size affected the RNFL thickness measured with HRT, whereas the axial length influenced the RNFL thickness and disc area measured with OCT. These variables must be taken into consideration when measuring eyes with the lower or upper boundary of the normal range.


Subject(s)
Nerve Fibers/ultrastructure , Optic Disk/anatomy & histology , Retinal Ganglion Cells/cytology , Adult , Aged , Aged, 80 and over , Aging/pathology , Eye/anatomy & histology , Female , Humans , Linear Models , Male , Middle Aged , Ophthalmoscopy , Reference Values , Tomography, Optical Coherence
15.
J Chromatogr A ; 1146(1): 61-6, 2007 Mar 30.
Article in English | MEDLINE | ID: mdl-17306277

ABSTRACT

A simple and sensitive method for the determination of abietic acid and dehydroabietic acid in food samples was developed using a fully automated method consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-mass spectrometry (LC/MS). These compounds were separated within 5min by HPLC using an ODS-3 column and 5mM ammonium formate/acetonitrile (10/90, v/v). Electrospray ionization conditions in the negative ion mode were optimized for MS detection of abietic acid and dehydroabietic acid. The optimum in-tube SPME conditions were 20draw/eject cycles of 40microL of sample using a Supel Q PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC/MS method, good linearity of the calibration curve (r>0.9998) was obtained in the concentration range from 0 to 50ng/mL, and the detection limits (S/N=3) of abietic acid and dehydroabietic acid were 2.9 and 2.1pg/mL, respectively. The in-tube SPME method showed above 75-fold greater sensitivity than the direct injection method (5microL injection). This method was applied successfully to analysis of food samples without interference peaks. The recoveries of abietic acid and dehydroabietic acid spiked into liquid samples were above 79%, and the relative standard deviations were below 6.6%. These compounds were detected at ng/mL or ng/g levels in various liquid or solid food samples contacted with paper.


Subject(s)
Abietanes/analysis , Chromatography, Liquid/methods , Food Analysis/methods , Mass Spectrometry/methods , Phenanthrenes/analysis , Solid Phase Microextraction/methods , Beverages/analysis , Calibration , Chromatography, Liquid/instrumentation , Food Analysis/instrumentation , Mass Spectrometry/instrumentation , Reproducibility of Results , Solid Phase Microextraction/instrumentation , Tea/chemistry , Wine/analysis
16.
Clin Exp Rheumatol ; 24(5): 546-54, 2006.
Article in English | MEDLINE | ID: mdl-17181924

ABSTRACT

OBJECTIVE: Methotrexate (MTX) is most widely used for the treatment of rheumatoid arthritis (RA). However, it has certain drawbacks with regard to individual differences in its therapeutic effects as well as the differences in the patients' response to MTX therapy. We investigated whether multi-drug resistance-1 (ABCB1) C3435T, reduced folate carrier-1 (RFC1) G80A, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) C347G and a 6bp-deletion polymorphism in the 3'-untranslated region of the thymidylase synthase (TYMS) gene are predictive of MTX sensitivity and its adverse effects. METHODS: Patients whose last maintenance dosage of MTX was 6 mg/week or those in whom MTX therapy was changed due to poor response to MTX were regarded as non-responders. The data of 124 RA patients who had received MTX treatment were retrospectively analyzed for polymorphisms in the ABCB1, RFC1, ATIC and TYMS genes, MTX sensitivity and MTX toxicity. RESULTS: There were no significant differences in MTX sensitivity among the genotypes of RFC1, ATIC and TYMS genes. ABCB1 3435TT cases included statistically significantly more non-responders than 3435CC cases according to univariate analysis (crude odds ratio (OR) = 8.91, p = 0.001) and multivariate analysis (adjusted OR = 8.78, p = 0.038). There were no significant differences in MTX toxicity among the genotypes of all the genes. CONCLUSION: These results suggested that the genetic diagnosis of ABCB1 C3435T can be applied to determine MTX sensitivity for the treatment of RA patients. However, further pharmacokinetics studies are required in this regard.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Drug Resistance, Multiple/genetics , Methotrexate/therapeutic use , Organic Anion Transporters/genetics , Polymorphism, Genetic , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/physiopathology , Female , Genotype , Health Status , Humans , Hydroxymethyl and Formyl Transferases/genetics , Joints/physiopathology , Male , Membrane Transport Proteins/genetics , Methotrexate/adverse effects , Middle Aged , Multienzyme Complexes/genetics , Nucleotide Deaminases/genetics , Retrospective Studies , Severity of Illness Index , Thymidylate Synthase/genetics , Treatment Outcome
17.
J Chromatogr A ; 1081(2): 218-24, 2005 Jul 22.
Article in English | MEDLINE | ID: mdl-16038212

ABSTRACT

A simple, rapid and sensitive method for the determination of five estrogens, estrone, 17beta-estradiol, estriol, ethynyl estradiol, and diethylstilbestrol, was developed using a fully automated method consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS). These estrogens were separated within 8 min by HPLC using an XDB-C8 column and 0.01% ammonia/acetonitrile (60/40, v/v) at a flow rate of 0.2 mL/min. Electrospray ionization conditions in the negative ion mode were optimized for MS/MS detection of the estrogens. The optimum in-tube SPME conditions were 20 draw/eject cycles of 40 microL of sample using a Supel-Q PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC/MS/MS method, good linearity of the calibration curve (r > or = 0.9996) was obtained in the concentration range from 10 to 200 pg/mL for all compounds examined. The limits of detection (S/N= 3) of the five estrogens examined ranged from 2.7 to 11.7 pg/mL. The in-tube SPME method showed 34-90-fold higher sensitivity than the direct injection method (5 microL injection). This method was applied successfully to the analysis of environmental water samples without any other pretreatment and interference peaks. Several surface water and wastewater samples were collected from the area around Asahi River, and estriol was detected at 35.7 pg/mL in the effluent of a sewage treatment plant. The recoveries of estrogens spiked into river waters were above 86%, except for estriol, and the relative standard deviations were below 0.9-8.8%.


Subject(s)
Chromatography, Liquid/methods , Environmental Monitoring/methods , Estrogens/analysis , Water Pollutants, Chemical/analysis , Automation , Chromatography, High Pressure Liquid/methods , Estrogens/isolation & purification , Online Systems , Spectrometry, Mass, Electrospray Ionization
18.
Rheumatology (Oxford) ; 44(10): 1233-7, 2005 Oct.
Article in English | MEDLINE | ID: mdl-15972352

ABSTRACT

OBJECTIVES: To clarify the initial onset time of osteonecrosis after the start of steroid treatment and its relation to the onset of abnormal lipid metabolism. METHODS: Animal models were prepared by administering methylprednisolone to rabbits using five different steroid regimens. RESULTS: A single, acute ischaemic event suggested by the frequency, size or number of necrotic foci within the proximal femur was not different among the groups. Histological evidence of osteonecrosis first occurred 1-2 weeks after initial steroid administration. At the same time there were significantly abnormal elevations in serum lipids, which persisted for between 1 and 2 weeks after the initial corticoid treatment. Triglycerides, total cholesterol and free fatty acids were markedly elevated in all groups; these lipid abnormalities were significantly present in the rabbits with osteonecrosis but not in the rabbits without osteonecrosis. CONCLUSIONS: This study shows that (i) osteonecrosis appears in rabbits shortly after corticoids are first administered, and (ii) osteonecrosis in rabbits is chronologically associated with the onset of hyperlipaemia and increased free fatty acids. This supports the occurrence of intraosseous fat embolism as a cause of osteonecrosis.


Subject(s)
Fatty Acids, Nonesterified/blood , Glucocorticoids/adverse effects , Hyperlipidemias/chemically induced , Methylprednisolone/adverse effects , Osteonecrosis/chemically induced , Animals , Disease Models, Animal , Female , Hyperlipidemias/complications , Osteonecrosis/blood , Osteonecrosis/etiology , Osteonecrosis/pathology , Rabbits , Time Factors
19.
Hepatology ; 34(6): 1128-34, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11732002

ABSTRACT

Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P <.05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue-PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP-negative cases, tissue-AFP-positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP-positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II-positive.


Subject(s)
Biomarkers , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Protein Precursors/metabolism , Prothrombin/metabolism , alpha-Fetoproteins/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Female , Humans , Immunohistochemistry , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Portal Vein/pathology , Survival Analysis
20.
Gan To Kagaku Ryoho ; 28(11): 1624-7, 2001 Oct.
Article in Japanese | MEDLINE | ID: mdl-11707995

ABSTRACT

We investigated whether the efficacy of peroral doxifluridine and hepatic arterial 5-FU infusion on synchronous liver metastasis of colorectal cancer could be predicted based on the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in the primary colorectal lesions. Ten patients with synchronous liver metastasis of colorectal cancer were given doxifluridine (600-800 mg/body/day) orally and 5-FU (500 mg/body, once or twice a week) through the hepatic artery following resection of the primary lesions between June 1996 and July 2001. The levels of TP and DPD in the primary lesions were determined by an enzyme-linked immunosorbent assay. The level of TP, DPD, and the ratio of TP/DPD in patients with partial response (n = 4) were 89.8 +/- 30.0 U/mg protein, 23.5 +/- 25.7 U/mg protein, and 3.8 +/- 1.4, respectively, while those in patients with no response or progressive disease (n = 6) were 41.8 +/- 9.7 U/mg protein, 25.8 +/- 15.8 U/mg protein, and 2.2 +/- 1.6, showing significant difference (p < 0.01) in the level of TP between the groups. These results indicate that determining the level of TS in primary colorectal lesions may be useful for predicting the efficacy of this regimen for patients with synchronous liver metastasis of colorectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/enzymology , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Oxidoreductases/metabolism , Thymidine Phosphorylase/metabolism , Aged , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Dihydrouracil Dehydrogenase (NADP) , Drug Administration Schedule , Female , Floxuridine/administration & dosage , Fluorouracil/administration & dosage , Hepatic Artery , Humans , Infusions, Intra-Arterial , Liver Neoplasms/mortality , Male , Middle Aged , Survival Rate
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