Hydroxylation of R(+)- and S(−)-Omeprazole after Racemic Dosing are Different among the CYP2C19 Genotypes

Pharmaceutical Research - To elucidate the stereoselective pharmacokinetics of omeprazole enantiomers and their metabolites after racemic IV dosing because there is little information about the...     

High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study

Santos‐Silva A R, Ribeiro A C P, Soubhia A M P, Miyahara G I, Carlos R, Speight P M, Hunter K D, Torres‐Rendon A, Vargas P A & Lopes M A (2011) Histopathology  58 , 1127–1135
High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study Aims: This multi‐centre analysis assessed the DNA content of TSCC in 37 young patients (<40 years) and 28 old patients (>50 years) and determined the correlation of DNA ploidy findings with clinicopathological data. Methods and results: Image cytometry was carried out using an automated cellular imaging system on Feulgen‐stained histological sections to obtain high‐fidelity DNA histograms. Among young patients, 37.8% were females compared to 18.7% in the older group (P = 0.002). In total, 48.6% patients were non‐smokers and 40.5% were non‐drinkers compared to 10.7% non‐smokers and non‐drinkers in the older group (P < 0.0001). TNM, clinical stage of disease and histological grade of differentiation did not differ between groups. Tumour aneuploidy was detected in 86.5% and tetraploidy in 24.3% young patients; this was significantly greater than in the older group where 64.3% were aneuploid (P < 0.0001) and 7.2% tetraploid (P < 0.0001). The mean values of DNA index (DI) and DNA heterogeneity index as well as the percentage of cells with DI exceeding 5N were higher in young patients (P < 0.0001). Conclusions: Young patients with TSCC represent a distinct clinical entity. The high incidence of DNA ploidy abnormalities suggest that they may have increased genomic instability and indicates underlying genetic differences between TSCC in young and older patients.     

Successful extracorporeal life support for life-threatening hypercapnia with bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans (BO) is a disease with a poor prognosis, and a key factor that limits long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). We here report a case of a 31-year woman with acute lymphatic leukemia, which was treated by chemotherapy and HSCT, and consequently developed BO 2 years after HSCT. A non-tuberculous mycobacterial infection occurred and showed gradual exacerbation. She started taking anti-mycobacterial drugs, but lost appetite, felt tired and finally lost consciousness one month after beginning medication. Arterial blood gas revealed marked hypercapnia. Using extracorporeal life support (ECLS), the carbon dioxide concentration was reduced and her consciousness recovered. To our knowledge, this is the first case in which ECLS was successfully used for hypercapnia in a patient with BO.     

Activities for laboratory medicine support after the Great East Japan Earthquake by the Japanese Society of Laboratory Medicine

The Great East Japan Earthquake caused a tragic tsunami and resulted in serious damage to north region of Japan on March 11, 2011. The Japanese Society of Laboratory Medicine, JSLM launched an ad hoc Committee to support Laboratory Medicine affairs in the affected area. We expected that laboratory testing demands would increase during the weeks following the disaster. We decided to support the use of Point-of-Care Testing. Many POCT devices use battery-powered analyzers. This is definite advantage for their use in areas with limited access to power and water supplies. We contacted many companies about the possibility of providing POCT devices, IVD reagents and/or any laboratory supplies including disposable materials. Finally, forty companies agreed to support this project and we received list of reagents materials for more than one hundred IVD tests. We entered this information on our web site and continued to update it as additional support was received. Once a request of support was received, communication were made to confirm the amount of material, the method of shipping/receipt and if any specific training that would be required for its use at the testing site. Also, we dispatched volunteer Medical Technologists for eight weeks to assist in the laboratory work. Some of the crucial points in recruiting volunteer laboratory professions are expenses and accommodations. We prepared not only accommodations but also transportation methods and covered all expenses including insurance and meals. Our relief activities have shown that Laboratory Medicine and Medical Technologists are useful in disaster-affected area.     

A SiPM-based isotropic-3D PET detector X'tal cube with a three-dimensional array of 1 mm(3) crystals

We are developing a novel, general purpose isotropic-3D PET detector X'tal cube which has high spatial resolution in all three dimensions. The research challenge for this detector is implementing effective detection of scintillation photons by covering six faces of a segmented crystal block with silicon photomultipliers (SiPMs). In this paper, we developed the second prototype of the X'tal cube for a proof-of-concept. We aimed at realizing an ultimate detector with 1.0 mm(3) cubic crystals, in contrast to our previous development using 3.0 mm(3) cubic crystals. The crystal block was composed of a 16 × 16 × 16 array of lutetium gadolinium oxyorthosilicate (LGSO) crystals 0.993 × 0.993 × 0.993 mm(3) in size. The crystals were optically glued together without inserting any reflector inside and 96 multi-pixel photon counters (MPPCs, S10931-50P, i.e. six faces each with a 4 × 4 array of MPPCs), each having a sensitive area of 3.0 × 3.0 mm(2), were optically coupled to the surfaces of the crystal block. Almost all 4096 crystals were identified through Anger-type calculation due to the finely adjusted reflector sheets inserted between the crystal block and light guides. The reflector sheets, which formed a belt of 0.5 mm width, were placed to cover half of the crystals of the second rows from the edges in order to improve identification performance of the crystals near the edges. Energy resolution of 12.7% was obtained at 511 keV with almost uniform light output for all crystal segments thanks to the effective detection of the scintillation photons.     

Semi-quantitative and simulation analyses of effects of γ rays on determination of calibration factors of PET scanners with point-like (22)Na sources

The uncertainty of radioactivity concentrations measured with positron emission tomography (PET) scanners ultimately depends on the uncertainty of the calibration factors. A new practical calibration scheme using point-like (22)Na radioactive sources has been developed. The purpose of this study is to theoretically investigate the effects of the associated 1.275 MeV γ rays on the calibration factors. The physical processes affecting the coincidence data were categorized in order to derive approximate semi-quantitative formulae. Assuming the design parameters of some typical commercial PET scanners, the effects of the γ rays as relative deviations in the calibration factors were evaluated by semi-quantitative formulae and a Monte Carlo simulation. The relative deviations in the calibration factors were less than 4%, depending on the details of the PET scanners. The event losses due to rejecting multiple coincidence events of scattered γ rays had the strongest effect. The results from the semi-quantitative formulae and the Monte Carlo simulation were consistent and were useful in understanding the underlying mechanisms. The deviations are considered small enough to correct on the basis of precise Monte Carlo simulation. This study thus offers an important theoretical basis for the validity of the calibration method using point-like (22)Na radioactive sources.     

Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression

Altered dorsal root ganglion (DRG) function is associated with neuropathic pain following spinal nerve injury. However, compression of the cauda equina and dorsal rhizotomy proximal to the DRG do not induce significant pain, whereas in the spinal nerve and peripheral nerve, injury distal to the DRG does induce neuropathic pain. Caspase signaling induces apoptosis, and caspase inhibitors prevent pain-related behavior. The degree of DRG neuronal apoptosis is thought to play a role in pain behavior. We suggest that differences in pain behavior according to the injury sites within the DRG may be related to imbalances in apoptotic injuries. The aim of this study was to determine which compression injury was more painful and to compare behavior with expression of tumor necrosis factor (TNF)-alpha in DRG and apoptosis in the DRG following crush injury to the L5 nerve root or L5 spinal nerve. Sprague–Dawley rats received a crush injury to the L5 spinal nerve (distal to the DRG), crush injury to the L5 nerve root (proximal to the DRG), or no crush injury (sham). Mechanical allodynia was determined by the von Frey test. Expression of TNF-alpha was compared among three groups using immunoblot findings. Furthermore, we compared the percentage of neurons injured in the DRG using immunostaining for apoptotic cells and localization of activated caspase 3. Mechanical allodynia was observed in both crush injury groups. The duration of mechanical allodynia in the distal crush group was significantly longer than in the proximal crush group (P < 0.05). TNF-alpha expression was increased in DRG neurons following injury. DRG apoptosis in the distal crush group was significantly higher than in the proximal group at each time point (P < 0.05). This study suggests that spinal nerve crush injuries produce a greater degree of DRG apoptosis than do corresponding nerve root crush injuries, and that the former injuries are associated with longer lasting mechanical allodynia. Thus, differences in the time course of mechanical allodynia might be associated with an imbalance in DRG apoptosis.     

Effects of hospital and surgeon case-volumes on postoperative complications and length of stay after esophagectomy in Japan

Purpose  The exact relationship between larger caseload volume and lower morbidity following esophagectomy has not been established. This study investigates the effect of surgical volumes on reducing postoperative complications and length of stay after esophagectomy. Methods  Patient and hospital data were collected electronically via a web-based questionnaire sent to surgeons in the Japan Surgical Society. Data were based on 642 patients treated with esophagectomy at 183 hospitals between November 1, 2006 and February 28, 2007. Multivariate analysis revealed that postoperative morbidity and length of stay regressed against hospital and surgeon volumes, patient characteristics, and details of the procedures. Results  In a logistic regression model, esophagectomies by surgeons performing a high volume of operations (>100 cases; “high case-volume surgeons”) were followed by a significantly lower rate of postoperative complications (odds ratio [OR], 0.49; 95% confidence interval (CI), 0.24–0.98, P = 0.04). In a proportional hazard model, high-volume surgeons reduced the length of stay significantly: the hazard ratio for medium casevolume surgeons (50–99 cases) was 1.53 [95% CI, 1.14–2.06, P = 0.00], whereas that for the highest case-volume surgeons was 1.34 [95% CI, 1.00–1.79, P = 0.05] vs the lowest case-volume surgeons. Neither postoperative complications nor length of stay were significantly associated with hospital volume. Conclusion  These findings indicate that morbidity after esophagectomy is more dependent on individual surgeon-specific skill than on hospital-based factors.