7-year survey of anesthesia for cesarean section--comparison of tetracaine and bupivacaine as intrathecal anesthetic agents

BACKGROUND: In our institution, spinal anesthesia is the first choice for cesarean section. After the introduction of bupivacaine in 2000 in Japan, the intrathecal anesthetic agent shifted from tetracaine to bupivacaine. We analyzed the anesthesia for cesarean section in recent 7 years and compared the anesthetic quality of tetracaine with that of bupivacaine. METHODS: The anesthetic records were reviewed in the patients who had received cesarean section between January 1998 and December 2004 at our institution. RESULTS:There were 10456 deliveries during the study period with a cesarean section rate of 28.2% (2947 cases). Ninety-one percent of cesarean section was performed under spinal anesthesia. Spinal anesthetic agent shifted from tetracaine to bupivacaine in 2000-2001, both of which was prepared as a hyperbaric solution and supplemented with 0.1 mg of morphine hydrocloride. Of the 2711 patients in whom a cesarean section was started under spinal anesthesia, 20 (0.7%) required conversion to general anesthesia. Three hundred eighteen patients (11.7%) required some analgesic supplementation. The incidence of intra-operative analgesic supplementation was greater in the patients anesthetized with hyperbaric tetracaine and morphine than in those anesthetized with hyperbaric bupivacaine and morphine (22.96% vs 4.20% ; P<0.01). The conversion rate from spinal to general anesthesia for cesarean section was 0.7%. CONCLUSIONS: Comparing these two intrathecal anesthetic agents, the rate of analgesic supplementation in those anesthetized with bupivacaine was lower than in those anesthetized with tetracaine. This suggests that bupivacaine provides the more profound blockade of the visceral pain than tetracaine, and is superior as a local anesthetic.     

Landiolol prevented myocardial ischemia in a patient with severe aortic stenosis undergoing total gastrectomy

Gastric cancer was detected in a 71-year-old man with severe aortic stenosis. According to ACC/AHA guidelines, aortic stenosis in the patient was so severe that noncardiac surgery was considered appropriate only after aortic valve replacement. However, due to uncontrollable hemorrhage from gastric cancer, total gastrectomy was urgently required. Surgery was performed under epidural and general anesthesia. Blood pressure and heart rate were stable during anesthetic induction, tracheal intubation and skin incision. Just after peritoneal incision, however, ST decreased significantly following hypertension and sinus tachycardia, which were controllable by deepening of the anesthetic level. This ST depression was dependent on heart rate but not blood pressure. Therefore, in order to control the heart rate and prevent myocardial ischemia, low dose landiolol was infused prophylactically. This agent regulated the heart rate below 85 beats per minute without inducing hypotension and prevented myocardial ischemia during the remaining anesthetic course including extubation and recovery from anesthesia. Although beta blocker is not generally recommended in patients with aortic stenosis, present case suggests that landiolol is effective and useful to prevent cardiac ischemia even in a patient with severe aortic stenosis.     

In these days molecule target drug in advanced non-small cell lung cancer

Conventionally advanced-non-small cell lung cancer have been treatment platinum and 90S new drug (paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan). However survival benefit is several months and treatment outcome have arrives at plateau. One molecule target drug have been attract attention. In this chapter mainly on gefitinib that refer that have been to data that clinical trial and EGFR gene mutation and resistance to EGFR-TKI. EGFR mutation with an initial dramatic response acquired resistance to the EGFR-TKI. Until the present that stracture have been participate T790M for acquired resistance and amplification of the MET gene is another mechanism of acquired resistance to EGFR-TKI.     

Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosis mediated by a caspase-dependent pathway

OBJECT: Shock waves have been experimentally applied to various neurosurgical treatments including fragmentation of cerebral emboli, perforation of cyst walls or tissue, and delivery of drugs into cells. Nevertheless, the application of shock waves to clinical neurosurgery remains challenging because the threshold for shock wave-induced brain injury has not been determined. The authors investigated the pressure-dependent effect of shock waves on histological changes of rat brain, focusing especially on apoptosis. METHODS: Adult male rats were exposed to a single shot of shock waves (produced by silver azide explosion) at overpressures of 1 or 10 MPa after craniotomy. Histological changes were evaluated sequentially by H & E staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The expression of active caspase-3 and the effect of the nonselective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were examined to evaluate the contribution of a caspase-dependent pathway to shock wave-induced brain injury. High-overpressure (> 10 MPa) shock wave exposure resulted in contusional hemorrhage associated with a significant increase in TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave application. Low-overpressure (1 MPa) shock wave exposure resulted in spindle-shaped changes in neurons and elongation of nuclei without marked neuronal injury. The administration of Z-VAD-FMK significantly reduced the number of TUNEL-positive cells observed 24 hours after high-overpressure shock wave exposure (p < 0.01). A significant increase in the cytosolic expression of active caspase-3 was evident 24 hours after high-overpressure shock wave application; this increase was prevented by Z-VAD-FMK administration. Double immunofluorescence staining showed that TUNEL-positive cells were exclusively neurons. CONCLUSIONS: The threshold for shock wave-induced brain injury is speculated to be under 1 MPa, a level that is lower than the threshold for other organs. High-overpressure shock wave exposure results in brain injury, including neuronal apoptosis mediated by a caspase-dependent pathway. This is the first report in which the pressure-dependent effect of shock wave on the histological characteristics of brain tissue is demonstrated.     

Effects of zonisamide on neurotransmitter release associated with inositol triphosphate receptors

To clarify the antiepileptic mechanisms of zonisamide (ZNS), we determined the interaction between ZNS and inositol-1,4,5-triphosphate receptor (IP3R) on exocytosis of GABA and glutamate in rat frontal cortex using microdialysis. ZNS increased basal GABA release, but not glutamate, concentration-dependently, and reduced concentration-dependently K⁺-evoked GABA and glutamate releases. Inhibition and activation of IP3R reduced and enhanced basal and K⁺-evoked GABA releases, respectively. The K⁺-evoked glutamate release was reduced and enhanced by IP3R antagonist and agonist, respectively, whereas basal glutamate release was increased by IP3R agonist but not affected by IP3R antagonist. Under extracellular Ca²⁺ depletion, IP3R agonist increased basal GABA and glutamate releases. The latter effects of IP3R agonist were weakly enhanced by ZNS, but such stimulatory action of ZNS was abolished by extracellular Ca²⁺ depletion. In contrast, ZNS inhibited the stimulatory effect of IP3R agonist on K⁺-evoked release. The stimulatory effect of IP3R agonist on basal release was regulated by N-type voltage-sensitive Ca²⁺ channel (VSCC) rather than P- and L-type VSCCs, whereas the stimulatory effect of IP3R agonist on K⁺-evoked release was regulated by P- and L-type VSCCs rather than N-type VSCC. These results suggest that ZNS-activated N-type VSCC enhances IP3R-associated neurotransmitter release during resting stage, whereas ZNS-induced suppression of P- and L-type VSCCs possibly attenuates IP3R-associated neurotransmitter release during neuronal hyperexcitability. Therefore, the combination of both of these two actions of ZNS on IP3R-associated neurotransmitter release mechanism seems to be involved, at least in part, in the mechanisms of antiepileptic and neuroprotective actions of ZNS.     

The development of a gene vector electrostatically assembled with a polysaccharide capsule

The purpose of this study was to develop a gene vector electrostatically assembled with a polysaccharide capsule. We used pDNA/polyethylenimine (PEI) complexes as efficient non-viral vectors. The pDNA/PEI complex was electrostatically encapsulated with various polysaccharides such as fucoidan, λ-carrageenan, xanthan gum, alginic acid, hyaluronic acid, and chondroitin sulfate (CS). The pDNA/PEI complex was shown as nanoparticles with positive ζ-potential, although the ternary complexes encapsulated with polysaccharides were shown as nanoparticles with negative ζ-potential. The pDNA/PEI complex showed high agglutination activity and cytotoxicity, although the ternary complexes encapsulated with polysaccharides had no agglutination activities and lower cytotoxicities. The pDNA/PEI complex showed high uptake and high transgene efficiency in B16-F10 cells. On the other hand, most of the ternary complexes show little uptake and gene expression. The ternary complex encapsulated by CS, however, showed comparable transgene efficiency to the pDNA/PEI complex. The uptake and gene expression of the ternary complex encapsulated by CS were significantly inhibited by hypothermia and the addition of CS, suggesting that the ternary complex was taken by CS-specific receptor-mediated energy-dependent process.     

Selective vulnerability of adult cochlear nucleus neurons to de-afferentation by mechanical compression

It is well established that the cochlear nucleus (CN) of developing species is susceptible to loss of synaptic connections from the auditory periphery. Less information is known about how de-afferentation affects the adult auditory system. We investigated the effects of de-afferentation to the adult CN by mechanical compression. This experimental model is quantifiable and highly reproducible. Five weeks after mechanical compression to the axons of the auditory neurons, the total number of neurons in the CN was evaluated using un-biased stereological methods. A region-specific degeneration of neurons in the dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) by 50% was found. Degeneration of neurons in the anteroventral cochlear nucleus (AVCN) was not found. An imbalance between excitatory and inhibitory synaptic transmission after de-afferentation may have played a crucial role in the development of neuronal cell demise in the CN. The occurrence of a region-specific loss of adult CN neurons illustrates the importance of evaluating all regions of the CN to investigate the effects of de-afferentation. Thus, this experimental model may be promising to obtain not only the basic knowledge on auditory nerve/CN degeneration but also the information relevant to the application of cochlear or auditory brainstem implants.     

A case of pathological complete response after treatment with uracil/tegafur (UFT) and folinate (Leucovorin) for liver metastasis of colon cancer

The patient is a 62-year-old female who underwent a right hemicolectomy for type-2 ascending colon cancer (moderately-differentiated adenocarcinoma, ss, n0, H0, P0, M0, stage II). Six months after the surgery, a solitary metastatic focus was expressed in the liver S3. Because schizophrenia was present concurrently, tegafur and uracil/folinate (UFT/Leucovorin) treatment was selected and performed for 3 months. Because the tumor shrank afterward, a partial hepatectomy was performed to obtain a curative resection. In a pathological examination of the resected focus, cicatricial/necrotic findings were observed, but no cancer cells were observed; hence, it was determined to be a pathological complete response (CR). In regard to chemotherapy for distant metastasis of colorectal cancer, many molecular-targeted agents are being introduced, thus resulting in more treatment options; however, depending on the patient's background, UFT/LV treatment can be an effective treatment option.     

Expression levels of drug-metabolizing enzyme, transporter, and nuclear receptor mRNAs in a novel three-dimensional culture system for human hepatocytes using micro-space plates

We evaluated a novel three-dimensional primary culture system using micro-space plates to determine the expression levels of 61 target (drug-metabolizing enzymes, transporters, and nuclear receptors) mRNAs in human hepatocytes. We measured mRNA expression levels of many target genes in four lots of cryopreserved human hepatocyte primary cells after 120 h of culture and compared differences in mRNA expression levels between cultures using traditional plates and those using micro-space plates. In this study, we show that the mRNA levels of many experimental targets in human hepatocytes before inoculation resemble the levels inside the human liver. Furthermore, we show that the rate of change of expression levels of many target mRNAs relative to the value before inoculation of the hepatocytes into micro-space plates was relatively smaller than the rate of change in hepatocytes inoculated into traditional plates. Pharmacokinetics-related examinations using this system are possible within a time frame of 120 h. We report that this novel three-dimensional culture system reproduces mRNA expression levels that are nearer to those in the liver in vivo and is an excellent platform for maintaining mRNA expression levels of drug-metabolizing enzymes and transporters when compared to common monolayer cultures.