High HNRNPA3 expression is associated with lymph node metastasis and poor prognosis in patients treated with radical cystectomy

ObjectiveWe sought to identify heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) expression in bladder cancer and its relationship to clinicopathological findings and prognosis.MethodsImmunohistochemical staining for HNRNPA3 was performed on 122 archived radical cystectomy specimens, with immunoreactivity being stratified on a 0 to 3 scale. The percentage of HNRNPA3 expressing tumor cells was calculated and multiplied by the staining score over an average of 5 areas to obtain a semiquantitative H-score (maximum value: 300). HNRNPA3 expression was categorized as high (≥80) or low (<80).ResultsThe patients’ median age was 70 years, and the median follow-up period was 39.4 months. High HNRNPA3 expression was significantly associated with lymph node metastasis (P= 0.014) and S100A8, S100A9 and uroplakin III expression (P= 0.028, 0.002, and 0.047, respectively). Log-rank tests indicated that high HNRNPA3 expression was significantly associated with disease progression and cancer-specific death (P= 0.013 and 0.006, respectively). In the Cox proportional hazards regression analysis, only lymph node metastasis was associated with disease progression and cancer-specific survival.ConclusionHNRNPA3 may be a new biomarker to predict biologically aggressive cancers and determine the appropriate treatment modality in patients after radical cystectomy.     

Adjuvant heparinization before manipulation of artery reduces early failure in primary arteriovenous fistula for end-stage renal disease patients

Clinical and Experimental Nephrology - Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable...     

Evaluation of noninvasive monitoring of preoxygenation

Administration of 100% oxygen before a "rapid-sequence" induction of anesthesia is recommended to prevent hypoxemia during induction. In the present study, we used a laser scattering analyzer to study the effectiveness of nitrogen washout from the lungs with oxygen wash into the lungs under two different preoxygenation regimens; 4 times of maximal breathing of 100% oxygen in one minute and normal tidal breathing of 100% oxygen for 3 minutes. The volunteers were healthy, ASA physical status 1, 22 to 33 years of age (26 +/- 3), 167 +/- 5 cm tall, and weighing 60 +/- 5 kg. Arterial blood saturation measured by a pulse oximeter was 97 while breathing 21% oxygen, and 99% while breathing 100% oxygen. Arterial oxygen tensions were 98 mmHg while breathing 21% oxygen, and over 480 mmHg while breathing 100% oxygen. Arterial carbon dioxide and end tidal carbon dioxide concentrations indicated that 4 time of maximal breathing in a minute leads to hyperventilation. The end-tidal oxygen concentration was not significantly different between before and after oxygen administration in two different regimens. End-tidal nitrogen concentration after tidal volume ventilation was lower than that of 4 breath in a minute. These results indicate that end-tidal nitrogen and oxygen could reflect arterial nitrogen and oxygen tensions during preoxygenation.     

Metabolism and distribution in the rat of peak E substance,a constituent inl-tryptophan product implicated in eosinophilia-myalgia syndrome

Peak E substance, 1,1-ethylidenebis[tryptophan], a contaminant found inl-tryptophan tablets, has been suggested as a causative agent for eosinophilia-myalgia syndrome (EMS). Peak E substance (50 mg/kg) was administered perorally to Wistar rats to determine its metabolism and distribution. A purification procedure using Bond Elut C₈ cartridges followed by HPLC was developed for the determination of peak E substance. The plasma concentration of peak E substance was 136 ng/ml at 1 h, and urinary excretion was 717 ng at 5 h and 10342 ng for 5–24 h, showing slow excretion of peak E substance into urine. The amount of peak E substance in the contents of the large intestine at 5 h, however, was 3136 g, much greater than urinary excretion for 24 h, indicating considerable transfer of peak E substance to large intestine without decomposition by gastric fluid in the stomach. We have detected for the first time not only the occurrence of peak E substance in plasma and urine, but also 1-methyl-tetrahydro--carboline-3-carboxylic acid (MTCA) in blood and organs of rats treated with peak E substance, thereby suggesting MTCA as one of the the metabolites of peak E substance. The amount of MTCA in the contents of the large intestine as well as in urine of rats treated with peak E substance was significantly greater than inl-tryptophantreated rats (50 mg/kg p.o.), demonstrating that MTCA was more readily produced from peak E substance than froml-tryptophan. Finally, we propose acetaldehydeinduced production of MTCA from peak E substance.     

Interaction of cyclosporin derivatives with the ATPase activity of human P-glycoprotein

1. P-glycoprotein, a 170–180 kDa membrane glycoprotein that mediates multidrug resistance, hydrolyses ATP to efflux a broad spectrum of hydrophobic agents. In this study, we analysed the effects of three MDR reversing agents, verapamil, cyclosporin A and [3′-keto-Bmt]-[Val^*]-cyclosporin (PSC 833), on the adenosine triphosphatase (ATPase) activity of human P-glycoprotein.
2. P-glycoprotein was immunoprecipitated with a monoclonal antibody (MRK-16) and the P-glycoprotein-MRK-16-Protein A-Sepharose complexes obtained were subjected to a coupled enzyme ATPase assay.
3. While verapamil activated the ATPase, the cyclosporin derivatives inhibited both the substrate-stimulated and the basal P-glycoprotein ATPase. No significant difference was observed between PSC 833 and cyclosporin A on the inhibition of basal P-glycoprotein ATPase activity. PSC 833 was more potent than cyclosporin A for the substrate-stimulated activity.
4. Kinetic analysis indicated a competitive inhibition of verapamil-stimulated ATPase by PSC 833.
5. The binding of 8-azido-[α-³²P]-ATP to P-glycoprotein was not altered by the cyclosporin derivatives, verapamil, vinblastine and doxorubicin, suggesting that the modulation by these agents of P-glycoprotein ATPase cannot be attributed to an effect on ATP binding to P-glycoprotein.
6. The interaction of the cyclosporin derivatives with ATPase of P-glycoprotein might present an alternative and/or additional mechanism of action for the modulation of P-glycoprotein function.

     

Anaesthetic management of a neonate with prenatally diagnosed cervical tumour and upper airway obstruction

We report the anaesthetic management of a mother, and airway management of a neonate with a prenatal diagnosis of cervical cystic hygroma causing upper airway obstruction. The mortality of such neonates due to upper airway obstruction is reported to exceed 20% following deliveries. Elective Caesarean section was performed under general anaesthesia, and in utero tracheal intubation of the neonate was accomplished under uninterrupted maternal-fetal circulation. By utilizing isoflurane and ritodrine, the heart rate of the neonate remained between 120 to 150 bpm for four minutes following uterine incision. We believe that it is important that a multidisciplinary approach be initiated for planning of airway management of the neonate soon after the diagnosis is made. Laryngoscopy blades larger than normal for neonates, and a portable Doppler to monitor the viability of the neonate were found to be useful in the management of the neonate during in utero tracheal intubation. Although estimated blood loss was not increased, nor did uterine atony occur postoperatively despite the use of ritodrine during Caesarean section, the efficacy and safety of ritodrine to delay placental detachment have not been proved.     

The impacts of breast conserving treatment and mastectomy on the quality of life in early-stage breast cancer patients

The quality of life (QOL) in 55 early-stage breast cancer patients after surgery was prospectively assessed using a newly developed Japanese QOL questionnaire: The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The impacts of breast conserving treatment (BCT) (22 cases) and modified radical mastectomy (MRM) (33 cases) on the QOL in those subjects were compared. The overall QOL scores were evaluated during four periods (before surgery, 0–2, 3–12, and 13–24 months after surgery). The mean scores of the four categories of the QOL-ACD (activity, physical condition, psychological condition, and social relationships) were also compared. The results demonstrated that a significant improvement was observed in the overall QOL scores among the three periods after surgery (0–2, 3–12, and 13–24 months) only in the BCT group (P<0.05). There were no significant differences between the two groups in the overall QOL scores during any of the three periods after surgery, and the mean score of the ‘psychological condition’ during 0–2 months period in the BCT group was significantly lower than that in the MRM group (P< 0.05).     

MR detection of cytoplasmic fat in clear cell renal cell carcinoma utilizing chemical shift gradient-echo imaging

We attempted to determine whether cytoplasmic fat in clear cell renal cell carcinoma (RCC) can be identified by chemical shift gradient-echo magnetic resonance imaging (CSI). CSI was performed for 22 clear cell RCCs and 30 other renal tumors (including 16 non-clear cell RCCs), all of which were surgically proven. Signal reduction in out-of-phase images of these tumors was retrospectively evaluated and compared. The signal loss ratio (SLR) was defined and calculated. Fat staining of specimens from 16 tumors was performed and correlated with SLR. SLR was significantly higher in clear cell RCCs than in non-clear cell RCCs (P < 0.001). There was a significant correlation between degree of fat staining positivity of the specimens and SLR (P < 0.01). When signal reduction in out-of-phase images suggested the diagnosis of clear cell RCC, correct diagnosis of this entity was made in resected renal tumors with sensitivity, specificity, and accuracy of 82%, 90%, and 87%, respectively. CSI can demonstrate cytoplasmic fat in clear cell RCCs, which helps to differentiate this entity from other RCCs.