Safety and effectiveness of lumbar cerebrospinal fluid drainage to prevent delayed cerebral ischemia after Fisher grade 3 subarachnoid hemorrhage with minimal intraventricular hemorrhage.

OBJECTIVE: Lumbar drainage (LD) of cerebrospinal fluid (CSF) is a simple way of clearing subarachnoid hemorrhage (SAH) and reducing the risk of delayed cerebral ischemia (DCI). We focused on Fisher grade 3 SAH with or without minimal intraventricular hemorrhage (IVH; Graeb score ≤5), which has a lower risk of cerebellar tonsillar herniation during LD. The aim of this study was to test the efficacy of LD with respect to reducing the risk of DCI in this patient group. METHODS: The authors retrospectively reviewed the medical records of 107 patients with Fisher grade 3 SAH with or without minimal IVH, admitted to two hospitals from 2013 to 2019. Patients were retrospectively divided into two groups: study group receiving standard therapy plus LD, or control group receiving standard therapy alone. Primary outcome measures were efficient in preventing DCI. RESULTS: One hundred and seven subjects were allocated to the control (n=79) or study (n=28) groups. Incidence of DCI was 28% (n=22) and 18% (n=5), respectively (P=0.448). Subgroup analysis for HH grade 3+4 (n=68) showed incidence of DCI of 24% (n=19) in the control group (n=50) and 7% (n=2) in the study group (n=18) (P=0.040). There were no LD-related complications. CONCLUSIONS: This study could not draw a meaningful conclusion about the overall efficacy of LD on DCI reduction due to small sample size. However, there was a significant reduction of DCI by LD in the HH 3+4 subpopulation. Larger-scale studies are required to confirm our results.

Oxytocin alleviates cellular senescence through oxytocin receptor-mediated extracellular signal-regulated kinase/Nrf2 signalling.

BACKGROUND: Oxytocin (OT) is a neuropeptide hormone that has many beneficial biological effects, including protection against age-related disorders. However, less is known about its role in intrinsic skin ageing, which is accelerated by an increase in senescent cell fraction in skin tissue. OBJECTIVES: To investigate the novel function and the underlying mechanism of OT in preventing cellular senescence in normal human dermal fibroblasts (NHDFs) isolated from the skin of female donors of different ages. METHODS: NHDFs from young and old donors were exposed to conditioned medium from senescent or control NHDFs in the presence or absence of 10 nmol L-1 OT for 3 days, and were continuously subcultured for 12 days. Subsequently, various age-associated signs of senescence including decreased proliferation rate, elevated p16 and p21 levels, and positivity for senescence-associated ß-galactosidase expression were examined. RESULTS: We found that OT suppressed senescence-associated secretory phenotype-induced senescence in NHDFs, and its effect depended on the age of the donor's NHDFs. The inhibitory effects of OT required signalling by OT receptor-mediated extracellular signal-regulated kinase/Nrf2 (nuclear factor erythroid 2-related factor 2). The age-dependent antisenescence effects of OT are closely related to hypermethylation of the OT receptor gene (OXTR). CONCLUSIONS: Our findings bring to light the role of OT in the prevention of skin ageing, which might allow development of new clinical strategies. What's already known about this topic? Senescent keratinocytes and fibroblasts accumulate with age in the skin and contribute to the loss of skin function and integrity during ageing. Senescent cells secrete senescence-associated secretory phenotype (SASP), which includes the release of proinflammatory cytokines such as interleukin (IL)-6 and IL-1, chemokines, extracellular matrix-remodelling proteases and growth factors. The neuropeptide oxytocin (OT) and its receptor (OXTR) have protective effects against various age-related disorders. What does this study add? OT suppressed SASP-induced cellular senescence in normal human dermal fibroblasts (NHDFs), depending on the age of the NHDFs' donor. The inhibitory effects of OT on cellular senescence required OXTR-mediated phosphorylation of extracellular signal-regulated kinase, which enhanced nuclear localization of Nrf2, a vital factor in the antioxidant defence system. The age-specific antisenescent effects of OT were closely related to hypermethylation of OXTR. What is the translational message? Our results suggest that OT and OXTR agonists could be clinically promising agents for the improvement of age-associated skin ageing, especially in women.

Procedural and obstetric outcomes after embryo reduction vs fetal reduction in multifetal pregnancy.

OBJECTIVE: To compare the obstetric outcome and incidence of procedure-related adverse events after embryo reduction (ER) vs fetal reduction (FR), in multifetal pregnancies undergoing reduction to twins or singletons. METHODS: We analyzed retrospectively data from multifetal pregnancies that underwent transvaginal ER (n = 181) at a mean gestational age of 7.6 weeks or transabdominal FR (n = 115) at a mean gestational age of 12.9 weeks between December 2006 and January 2017. FR was performed after a detailed fetal anomaly scan. The two groups were compared with respect to obstetric outcomes, such as incidence of miscarriage, early or late preterm delivery, maternal complications and fetal loss, and procedure-related adverse events, including incidence of subchorionic hematoma and procedure-related fetal loss. RESULTS: Compared with pregnancies that underwent ER, the incidence of procedure-related fetal loss was lower in the FR group (7.2% vs 0.9%; P = 0.039; odds ratio (OR), 0.12; 95% CI, 0.02-0.89). Mean gestational age at delivery for twins was 34.2 weeks in the ER group and 35.7 weeks in the FR group (P = 0.014). Compared with the ER group, the FR group had lower miscarriage (8.8% vs 2.6%; P = 0.045; OR, 0.28; 95% CI, 0.08-0.97) and overall fetal loss (13.3% vs 5.2%; P = 0.031; OR, 0.36; 95% CI, 0.14-0.91) rates. CONCLUSIONS: The FR procedure is, overall, a better and safer approach to reducing morbidity and mortality in multifetal pregnancies. Spontaneous demise of one fetus may occur after ER, and FR has the advantage that chorionic villus sampling and ultrasound screening for increased nuchal translucency and anatomical defects can be conducted before the procedure. The ER approach is still reasonable when a patient's religious or other ethical concerns are of primary importance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Interferon-inducible T-cell alpha chemoattractant (ITAC) induces the melanocytic migration and hypopigmentation through destabilizing p53 via histone deacetylase 5: a possible role of ITAC in pigment-related disorders.

BACKGROUND: Cell migration plays a major role in the immune response and in tumorigenesis. Interferon-inducible T-cell alpha chemoattractant (ITAC) elicits a strong chemotactic response from immune cells. OBJECTIVES: To examine the effect of ITAC on melanocyte migration and pigmentation and its involvement in related disorders, and to investigate potential key players in these processes. METHODS: Human melanocytes or melanoma cells were treated with ITAC and a migration assay was carried out. Global gene expression analysis was performed to find genes regulated by ITAC treatment. The function of key players involved in ITAC-induced cellular processes was addressed using knockdown or overexpression experiments in combination with ITAC treatment. ITAC expression in the inflammation-associated hypopigmentary disorder, vitiligo, was examined. RESULTS: Among CXCR3 ligands, only ITAC induced melanocyte migration. ITAC treatment upregulated the expression of histone deacetylase 5 (HDAC5) and downregulated that of p53, a known target of HDAC5. Through knockdown or overexpression of HDAC5 and p53, we confirmed that HDAC5 mediates ITAC-induced migration by decreasing levels of p53 via deacetylation. In addition, ITAC treatment could decrease pigmentation in a p53- and HDAC5-dependent manner. Finally, the increased migration of human melanoma cells by ITAC treatment and the increased ITAC expression in the epidermis of vitiligo skin were verified. CONCLUSIONS: This study provides in vitro evidence for the migratory and hypopigmentation effects of ITAC on melanocytic cells, gives translational insights into the roles of ITAC in pathological conditions, and suggests that HDAC5 and its substrate p53 are potent targets for regulating ITAC-induced cellular processes.

Effects of cilostazol on the pharmacokinetics of carvedilol after oral and intravenous administration in rats.

This study was designed to investigate the effects of cilostazol on the pharmacokinetics of carvedilol following oral or intravenous administration of carvedilol in rats. Clinically carvedilol and cilostazol can be prescribed for treatment of cardiovascular diseases. Carvedilol and cilostazol are all substrates of CYP2C9 enzymes. Carvedilol was administered orally or intravenously without or with oral administration of cilostazol to rats. The effects of cilostazol on cytochrome P450 (CYP) 2C9 activity and P-gp activity were also evaluated. Cilostazol inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibitory concentration (IC(50)) of 8.7 µM. Compared with the control group, the area under the plasma concentration-time curve (AUC) of carvedilol was significantly (P < 0.05) increased by 38.0%. The peak concentration (C(max)) was significantly (P < 0.05) increased by 49.2% in the presence of cilostazol after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.15 - 1.38-fold, and the absolute bioavailability (A.B.) of carvedilol in the presence of cilostazol was significantly (P < 0.05) higher than that of the control. After intravenous administration, the AUC of carvedilol was significantly (P < 0.05) increased by 19.2% compared to that in the control by cilostazol. These results suggest that cilostazol effectively inhibited the metabolism of carvedilol. The increased oral bioavailability of carvedilol might be due to the inhibition of CYP2C9-mediated metabolism of carvedilol in the liver by cilostazol.

Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

BACKGROUND: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). METHODS: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. RESULTS: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. CONCLUSIONS: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

The adequacy of the distal resection margin after preoperative chemoradiotherapy for rectal cancer.

AIM: The study aimed to determine the adequacy of the distal margin in patients having preoperative chemoradiotherapy (CRT) followed by restorative surgery for rectal cancer. METHOD: A total of 368 patients with locally advanced rectal cancer treated for cure at our institution between July 1999 and March 2009 were included in the study. All underwent preoperative CRT and sphincter-sparing surgery. The distal margin and other factors were examined for their effect on recurrence and survival. The median duration of follow-up was 48 months. RESULTS: The length of distal margin ranged from 0 to 9.0 cm (median 1.5 cm). The pelvic control and disease-free survival rates at 5 years for patients with a margin of ≤ 3 mm were no different from those in whom it was > 3 mm (P = 0.6 and 0.8). The 5-year pelvic control rates between the ≤ 3 mm and > 3 mm groups were 66.7 and 86.2% in patients with a ypT3-4 tumour (P = 0.049) and 70.0 and 89.1% in patients who showed no response to CRT (P = 0.039). CONCLUSION: The results suggest that a distal margin of < 3 mm in the surgical specimen after preoperative CRT is associated with a lower rate of pelvic tumour control at 5 years in patients with Stage ypT3-4 tumours or in those who do not respond to CRT.

Fabrication and characterization of fully flattened carbon nanotubes: a new graphene nanoribbon analogue.

Graphene nanoribbons (GNR) are one of the most promising candidates for the fabrication of graphene-based nanoelectronic devices such as high mobility field effect transistors (FET). Here, we report a high-yield fabrication of a high quality another type of GNR analogue, fully flattened carbon nanotubes (flattened CNTs), using solution-phase extraction of inner tubes from large-diameter multi-wall CNTs (MWCNTs). Transmission electron microscopy (TEM) observations show that flattened CNTs have width of typically 20 nm and a barbell-like cross section. Measurements of the low-bias conductance of isolated flattened CNTs as a function of gate voltage shows that the flattened CNTs display ambipolar conduction which is different from those of MWCNTs. The estimated gap based on temperature dependence of conductivity measurements of isolated flattened CNTs is 13.7 meV, which is probably caused by the modified electronic structure due to the flattening.

Prolonged inspiratory time produces better gas exchange in patients undergoing laparoscopic surgery: A randomised trial.

BACKGROUND: Laparoscopic surgery performed with a patient in the Trendelenburg position is known to have adverse effects on pulmonary gas exchange and respiratory mechanics. We supposed that prolonged inspiratory time can improve gas exchange at lower airway pressure. METHODS: One hundred patients undergoing gynaecologic laparoscopic surgery were randomly assigned to one of four groups: conventional inspiratory-to-expiratory (I : E) ratio (Group 1 : 2), I : E ratio of 1 : 1 (Group 1 : 1), 2 : 1 (Group 2 : 1), or 1 : 2 with external positive end-expiratory pressure (PEEP) of 5 cmH2 O (Group 1 : 2 PEEP). Tidal volume was set to 6 ml/kg, and I : E ratio was adjusted at the onset of pneumoperitoneum. Arterial blood gas analysis with measurements of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2 /FiO2 ), and physiologic dead space-to-tidal volume ratio (VD /VT ) was performed 15 min after anaesthetic induction (T1), and 30 (T2) and 60 min (T3) after onset of CO2 insufflation. RESULTS: PaO2 /FiO2 at T3 in Groups 1 : 1, 2 : 1, and 1 : 2 PEEP were higher than Group 1 : 2. The partial pressure of arterial carbon dioxide at T3 in Group 2 : 1 was lower than the other groups. The VD /VT at T2 and T3 were lower in Groups 1 : 1 and 2 : 1 than Groups 1 : 2 and 1 : 2 PEEP. Peak or plateau airway pressure was higher in Group 1 : 2 PEEP than the other groups. CONCLUSIONS: A prolonged inspiratory time demonstrated a beneficial effect on oxygenation. Furthermore, it showed better CO2 elimination without elevating the peak or plateau airway pressure compared with applying external PEEP. In terms of gas exchange and respiratory mechanics, a prolonged inspiratory time appears to be superior to applying external PEEP in patients undergoing laparoscopic surgery in the Trendelenburg position.

Effects of licochalcon A on the pharmacokinetics of losartan and its active metabolite, EXP-3174, in rats.

Losartan and licochalcon A interact with cytochrome P-450 (CYP) enzymes and P-glycoprotein (P-gp), and the increase in the use of health supplements may result in licochalcon A being taken concomitantly with losartan to treat or prevent cardiovascular diseases as a combination therapy. The effect of licochalcon A, a natural flavonoid, on the pharmacokinetics of losartan and its active metabolite, EXP-3174, was investigated in rats. Pharmacokinetic parameters of losartan and EXP-3174 were determined after oral administration of losartan (9 mg/kg) to rats in the presence or absence of licochalcon A (0.5, 2.5 and 10 mg/kg). The effect of licochalcon A on P-glycoprotein (P-gp) as well as CYP3A4 and 2C9 activities was also evaluated. Licochalcon A inhibited CYP3A4 and CYP2C9 enzyme activities with 50% inhibition concentrations (IC50) of 2.0 and 0.1 microM, respectively. In addition, licochalcon A significantly enhanced the cellular accumulation of rhodamine-123 in a concentration-dependent manner in MCF-7/ADR cells overexpressing P-gp. The pharmacokinetic parameters of losartan were significantly altered by licochalcon A. Licochalcon A (2.5 mg/kg or 10 mg/kg) increased AUC0-infinity of losartan by 33.4-63.2% and Cmax of losartan by 34.0-62.8%. The total body clearance (CL/F) was significantly decreased (2.5 mg/kg, p < 0.05; 10 mg/kg, p < 0.01) by licochalcon A. Consequently, the absolute bioavailability of losartan in the presence of licochalcon A increased significantly (2.5 mg/kg, p < 0.05; 10 mg/kg, p < 0.01) compared to that in the control group. The relative bioavailability (R.B.) of losartan was 1.15- to 1.63-fold greater than that of the control group. However, there was no significant change in Tmax and t1/2 of losartan in the presence of licochalcon A. Licochalcon A (10 mg/kg) increased the AUC0-infinity of EXP-3174 but this was not significant. Furthermore, concurrent use of licochalcon A (10 mg/kg) significantly decreased the metabolite-parent AUC ratio (M.R.) by 20%, suggesting that licochalcon A inhibited the CYP-mediated metabolism of losartan to its active metabolite, EXP-3174. In conclusion, the enhanced oral bioavailability of losartan in the presence of licochalcon A may mainly result from decreased P-gp-mediated efflux transporter in the small intestine and from the inhibition of CYP 3A- and CYP2C9-mediated metabolism in the small intestine and liver and/or from the reduction of total body clearance of losartan by licochalcon A.

Mucin 1 enhances the tumor angiogenic response by activation of the AKT signaling pathway.

Although the hyper-glycosylated transmembrane protein Mucin 1 (MUC1) is aberrantly overexpressed in human breast carcinoma, the biological significance of MUC1 overexpression is unclear. This study showed that MUC1 expression promoted the synthesis and secretion of vascular endothelial growth factor (VEGF) through the AKT signaling pathway. Increase VEGF production through MUC1 expression had a number of effect. First, MUC1 transfection increased expression of VEGF in breast cancer cells. Second, MUC1-mediated VEGF induction was attenuated by a chemical inhibitor of AKT or MUC1 knock-down by MUC1 siRNA. Third, MUC1 expression led to the activation of insulin-like growth factor-1 receptor, which correlated with VEGF expression. In addition, when MDA-MB-231 human breast cancer cells were directly injected into NOD/SCID mice, MUC1 expression accelerated xenograft tumor growth in vivo. Finally, MUC1 expression enhanced tumor growth and angiogenesis in a PyMT-MMTV/hMUC1 transgenic mouse model. Concurrent with these results, analysis of a human tissue microarray identified a high correlation between MUC1 and VEGF expression in human breast carcinoma. The current report is the first to demonstrate that MUC1 expression promotes angiogenesis in human breast cancer in vivo and in vitro.

Novel tumor suppressive function of Smad4 in serum starvation-induced cell death through PAK1-PUMA pathway.

DPC4 (deleted in pancreatic cancer 4)/Smad4 is an essential factor in transforming growth factor (TGF)-ß signaling and is also known as a frequently mutated tumor suppressor gene in human pancreatic and colon cancer. However, considering the fact that TGF-ß can contribute to cancer progression through transcriptional target genes, such as Snail, MMPs, and epithelial-mesenchymal transition (EMT)-related genes, loss of Smad4 in human cancer would be required for obtaining the TGF-ß signaling-independent advantage, which should be essential for cancer cell survival. Here, we provide the evidences about novel role of Smad4, serum-deprivation-induced apoptosis. Elimination of serum can obviously increase the Smad4 expression and induces the cell death by p53-independent PUMA induction. Instead, Smad4-deficient cells show the resistance to serum starvation. Induced Smad4 suppresses the PAK1, which promotes the PUMA destabilization. We also found that Siah-1 and pVHL are involved in PAK1 destabilization and PUMA stabilization. In fact, Smad4-expressed cancer tissues not only show the elevated expression of PAK1, but also support our hypothesis that Smad4 induces PUMA-mediated cell death through PAK1 suppression. Our results strongly suggest that loss of Smad4 renders the resistance to serum-deprivation-induced cell death, which is the TGF-ß-independent tumor suppressive role of Smad4.

Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups.

BACKGROUND: Despite significant differences in age of onset and incidence of breast cancer between Caucasian (CA), African-American (AA) and Korean (KO) women, little is known about differences in BRCA1/2 mutations in these populations. The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations and the association between BRCA1/2 mutation status and secondary malignancies among young women with breast cancer in these three racially diverse groups. METHODS: Patients presenting to our breast cancer follow-up clinics selected solely on having a known breast cancer diagnosis at a young age (YBC defined as age <45 years at diagnosis) were invited to participate in this study. A total of 333 eligible women, 166 CA, 66 AA and 101 KO underwent complete sequencing of BRCA1/2 genes. Family history (FH) was classified as negative, moderate or strong. BRCA1/2 status was classified as wild type (WT), variant of uncertain significance (VUS) or deleterious (DEL). RESULTS: DEL across these three racially diverse populations of YBC were nearly identical: CA 17%, AA 14% and KO 14%. The type of DEL differed with AA having more frequent mutations in BRCA2, compared with CA and KO. VUS were predominantly in BRCA2 and AA had markedly higher frequency of VUS (38%) compared with CA (10%) and KO (12%). At 10-year follow-up from the time of initial diagnosis of breast cancer, the risk of secondary malignancies was similar among WT (14%) and VUS (16%), but markedly higher among DEL (39%). CONCLUSIONS: In these YBC, the frequency of DEL in BRCA1/2 is remarkably similar among the racially diverse groups at 14%-17%. VUS is more common in AA, but aligns closely with WT in risk of second cancers, age of onset and FH.

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.

In patients with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer, treatment with trastuzumab has been shown to markedly improve the outcome. We investigated the role of trastuzumab on brain metastasis (BM) in HER2-positive breast cancer patients. From 1999 to 2006, 251 patients were treated with palliative chemotherapy for HER2-positive metastatic breast cancer at Samsung Medical Center. The medical records of these patients were analysed to study the effects of trastuzumab on BM prevalence and outcomes. Patients were grouped according to trastuzumab therapy: pre-T (no trastuzumab therapy) vs post-T (trastuzumab therapy). The development of BM between the two treatment groups was significantly different (37.8% for post-T vs 25.0% for pre-T, P=0.028). Patients who had received trastuzumab had longer times to BM compared with patients who were not treated with trastuzumab (median 15 months for post-T group vs 10 months for pre-T group, P=0.035). Time to death (TTD) from BM was significantly longer in the post-T group than in the pre-T group (median 14.9 vs 4.0 months, P=0.0005). Extracranial disease control at the time of BM, 12 months or more of progression-free survival of extracranial disease and treatment with lapatinib were independent prognostic factors for TTD from BM.

The usefulness of preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for localization in laparoscopic colorectal surgery.

BACKGROUND: Laparoscopic surgery for colorectal neoplasm requires precise tumor localization. The authors have assessed the safety and efficacy of colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for tumor localization in laparoscopic colorectal surgery. METHODS: Between July 2004 and January 2007, 63 patients underwent colonoscopic tattooing using prepackaged sterile India ink before laparoscopic surgery of colorectal tumors. Patient medical records and operation videos were retrospectively assessed. RESULTS: Tattoos were visualized intraoperatively in 62 (98.4%) of the 63 patients, and colorectal tumors were accurately localized in 61 patients (96.8%). In one patient, the tattoo could not be detected, whereas in another patient, it was visualized but the serosal surface of the rectosigmoid colon was stained diffusely. Both of these patients underwent intraoperative colonoscopy. Localized leakages of ink were identified in six patients (9.5%) during surgery. However, five of these patients had no symptoms, and the sixth patient, who underwent polypectomy and tattooing simultaneously, felt mild chilling without fever or abdominal pain. CONCLUSIONS: Preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink is a safe and effective method for tumor localization in laparoscopic colorectal surgery.

Influence of the baricity of a local anaesthetic agent on sedation with propofol during spinal anaesthesia.

BACKGROUND: This study examined the effect of different levels of spinal anaesthesia, induced by solutions of different baricity but containing the same amount of local anaesthetic agent, on the requirement for sedation with propofol. METHODS: Thirty-six patients undergoing varicose vein surgery under spinal anaesthesia were randomly allocated to receive tetracaine 15 mg in 3 ml of either glucose 5% (hyperbaric) or CSF (isobaric). I.V. propofol was started 5 min after the intrathecal injection and was titrated to maintain a bispectral index (BIS) score of 65-75. The propofol requirements to maintain this range in the two groups were compared every 5 min. RESULTS: The propofol requirement was always lower in the hyperbaric group, with the differences becoming statistically significant 20 min after the intrathecal injection. Total consumption of propofol over the 55 min of the study was also less in the hyperbaric group. CONCLUSION: The known difference in level of spinal anaesthetic block induced by solutions of different baricity, but the same dose of local anaesthetic, was associated with different requirements for propofol sedation as determined by BIS assessment.

A randomized trial of crystalloid versus colloid solution for prevention of hypotension during spinal or low-dose combined spinal-epidural anesthesia for elective cesarean delivery.

BACKGROUND: Spinal anesthesia for cesarean delivery is commonly associated with hypotension and nausea and vomiting, and preload with crystalloid or colloid solution is widely recommended. Low-dose spinal via the combined spinal-epidural technique appears to cause less hypotension and nausea and vomiting. The aim of this study was to investigate whether the combined use of colloid preload and combined spinal-epidural technique might further reduce the rates of these symptoms. METHODS: Women undergoing elective cesarean delivery were randomly allocated to one of four groups (50 in each) to receive crystalloid preload before spinal anesthesia, colloid preload before spinal anesthesia, crystalloid preload before combined spinal-epidural anesthesia, and colloid preload before combined spinal-epidural anesthesia. The incidences of hypotension and nausea and vomiting were compared. Spinal anesthesia was performed with 0.5% hyperbaric bupivacaine 9 mg and fentanyl 20 microg, and combined spinal-epidural anesthesia with 0.5% hyperbaric bupivacaine 6 mg + fentanyl 20 microg followed by epidural injection of 0.25% bupivacaine 10 mL. RESULTS: The frequencies of hypotension were 44%, 18%, 24%, and 20% in crystalloid preload-spinal anesthesia, colloid preload-spinal anesthesia, crystalloid preload-combined spinal epidural anesthesia, and colloid preload-combined spinal epidural anesthesia groups, respectively. The frequencies of nausea and vomiting were 20%, 2%, 8%, and 4% in respective groups. CONCLUSION: Colloid preload and low-dose spinal anesthesia alone or in combination lowered the incidences of hypotension and nausea. However, the combination of two methods failed to demonstrate further decreases in the incidence of the symptoms compared to the colloid-spinal anesthesia or crystalloid-combined spinal-epidural anesthesia groups.

Paraesthesia during the needle-through-needle and the double segment technique for combined spinal epidural anaesthesia.

Paraesthesia during regional anaesthesia is an unpleasant sensation for patients and, more importantly, in some cases it is related to neurological injury. Relatively few studies have been conducted on the frequency of paraesthesia during combined spinal epidural anaesthesia. We compared two combined spinal epidural anaesthesia techniques: the needle-through-needle technique and the double segment technique in this respect. We randomly allocated 116 parturients undergoing elective Caesarean section to receive anaesthesia using one of these techniques. Both techniques were performed using a 27G pencil point needle, an 18G Tuohy needle, and a 20G multiport epidural catheter from the same manufacturer. The overall frequency of paraesthesia was higher in the needle-through-needle technique group (56.9% vs. 31.6%, p = 0.011). The frequency of paraesthesia at spinal needle insertion was 20.7% in the needle-through-needle technique group and 8.8% in the double segment technique group; whereas the frequency of paraesthesia at epidural catheter insertion was 46.6% in the needle-through-needle technique group and 24.6% in the double segment technique group.

Combined low-dose spinal-epidural anesthesia versus single-shot spinal anesthesia for elective cesarean delivery.

Combined spinal-epidural anesthesia balancing low-dose intrathecal bupivacaine/fentanyl and low-dose epidural bupivacaine may be more useful than single-shot spinal anesthesia for cesarean delivery in reducing incidences of adverse effects such as hypotension and nausea and in shortening motor recovery. Combined spinal-epidural anesthesia (n=50) or spinal anesthesia (n=50) was randomly performed in 100 parturients. Intrathecal bupivacaine 6 mg added by fentanyl 20 mug followed after 5 min by 10 mL of 0.25% epidural bupivacaine were used for combined spinal-epidural and intrathecal bupivacaine 9 mg with fentanyl 20 mug for spinal anesthesia. The initial sensory block level was higher in the spinal group (P<0.001), although the maximum levels were the same (T3). Complete surgical anesthesia was achieved and no patient complained of intraoperative pain in either group. Patients in the spinal group had denser motor block in the extremities and a higher incidence of hypotension (P<0.05) and nausea and vomiting (P<0.05). Motor recovery was faster in the combined spinal-epidural group (P<0.001). We concluded that combined spinal-epidural anesthesia using low-dose local anesthetic-opioid spinal anesthesia and routine epidural supplementation before surgery had some potential advantages over single-shot spinal anesthesia in the lower incidences of adverse effects and quicker recovery.

Antioxidative effects of 7-hydroxy-3-methoxy-cadalene extracted from Zelkova serrata on 4-(methylinitros amino)-1-(3-pyridyl)-1-butanone-induced oxidative stress in A/J mice.

Effects of 7-hydroxy-3-methoxy-cadalene (cadalene) extracted from Zelkova serrata on 4-(methylinitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced oxidative stress were examined using A/J mice. NNK (65 microg/ml water) was orally administered to 20 mice for 7 weeks, followed by free feeding of a commercial diet, not containing cadalene, for 2 weeks. The control group was maintained without NNK and cadalene administration, and treatment groups with NNK and cadalene (6.25, 25, 100 mg/kg feed) feeding for 25 weeks. The glutathione concentration of cadalene-treated (65 microg/ml water) group was significantly higher than that of the group treated only with NNK (p < 0.05). The results of our study strongly indicate that cadalene exerts antioxidative effect on NNK-induced lung tumorigenesis in A/J mice.