The prognostic value of pretreatment of systemic inflammatory responses in patients with urothelial carcinoma undergoing radical cystectomy.

BACKGROUND: Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma undergoing radical cystectomy. METHODS: The study cohort consisted of 419 patients with a median follow-up of 37.7 months. The SIRs used for each described prognostic nomogram are consistent with previously published data: C-reactive protein, albumin, white cell count, neutrophil count, lymphocyte count, and platelet count. Primary end point was disease-specific survival (DSS) and overall survival (OS) after surgery. Cox regression models were used to determine the time to disease-specific and overall mortality. Multivariate regression coefficients of the predictors were used to develop nomograms for predicting 5-year DSS and OS probability. RESULTS: Multivariate Cox regression analyses revealed that albumin, lymphocyte count, and platelet count were significantly associated with a significantly increased risk for death from bladder cancer. The nomograms including each index were developed to predict the probability of 5-year DSS and OS after radical cystectomy. The C statistics were 77.8% and 77.3%, respectively, and exceeded the 2002 AJCC (72.0% and 70.3%, respectively). In the decision curve analyses, the nomograms including SIR demonstrated higher net benefit gains compared with the models without SIR. CONCLUSIONS: Cellular components of SIR have better prognostic values compared with acute-phase protein in patients undergoing radical cystectomy for bladder cancer.

Genetic variants in the CYP24A1 gene are associated with prostate cancer risk and aggressiveness in a Korean study population.

BACKGROUND: Vitamin D-deactivating enzyme CYP24A1 had controversial effects on prostate cancer risk; the genetic study also showed the controversial results. Therefore, we identified the relationships between polymorphisms in CYP24A1 and prostate cancer in a Korean cohort. METHODS: We evaluated the association between 21 single-nucleotide polymorphisms (SNPs) in the CYP24A1 and prostate cancer in Korean men (272 prostate cancers and 173 controls). BPH patients with high PSA or abnormal digital rectal examination who underwent negative prostate biopsy were enrolled in the control group. Twenty-one SNPs in the CYP24A1 were selected from the International HapMap database and the NCBI database with calculation of minor allele frequency and linkage disequilibrium, preferably including the SNPs that were nonsynonymous and located within exons. We also investigated the association between 21 SNPs in the CYP24A1 gene and known clinical characteristics, such as the PSA level, clinical stage, pathological stage and Gleason score. RESULTS: The statistical analysis suggested that five CYP24A1 sequence variants (rs2248461-odds ratio (OR): 0.63, rs2248359-OR: 0.65, rs6022999-OR: 0.65, rs2585428-OR: 0.46, rs4809959-OR: 0.52) had a significant association with prostate cancer risk after multiple comparisons by a method of false discovery rate. Logistic analyses of the CYP24A1 polymorphisms with several prostate cancer-related factors showed that several SNPs were significant: four SNPs to PSA level, three to clinical stage, two to pathological stage and two SNPs to the Gleason score. CONCLUSIONS: The results of this study suggest that some CYP24A1 gene polymorphisms might be associated with the risk of prostate cancer in Korean men. Five CYP24A1 sequence variants showed the significance to predict prostate cancer, and several SNPs of CYP24A1 gene had an important finding to predict prostate cancer-related factors. However, these results should be validated in future large-scale studies.

A dose-response study of remifentanil for attenuation of the hypertensive response to laryngoscopy and tracheal intubation in severely preeclamptic women undergoing caesarean delivery under general anaesthesia.

BACKGROUND: Remifentanil is known to attenuate the cardiovascular responses to tracheal intubation. We determined effective doses (ED(50)/ED(95)) of remifentanil to prevent the pressor response to tracheal intubation in patients with severe preeclampsia. METHODS: Seventy-five women with severe preeclampsia were randomly allocated to one of five remifentanil dose groups (0.25, 0.50, 0.75, 1.0, or 1.25 µg/kg) given before induction of anaesthesia using thiopental 5 mg/kg and suxamethonium 1.5 mg/kg. Systolic arterial pressure, heart rate and plasma catecholamine concentrations were measured. Neonatal effects were assessed by Apgar scores and umbilical cord blood gas analysis. A dose was considered effective when systolic arterial pressure did not exceed 160 mmHg for more than 1 min following tracheal intubation. RESULTS: Baseline systolic blood pressure and heart rate did not differ among the groups. The intubation-induced increases of heart rate and blood pressure were attenuated in a dose-dependent manner by remifentanil. ED(50) and ED(95) were 0.59 (95% CI 0.47-0.70) µg/kg and 1.34 (1.04-2.19)µg/kg, respectively. Norepinephrine concentrations remained unaltered following intubation but increased significantly at delivery, with no differences between the groups. Apgar scores and umbilical arterial and venous pH and blood gas values were comparable among the groups. Two women each in the 1.0 and 1.25 µg/kg groups received ephedrine for hypotension defined as systolic arterial pressure <90 mmHg. CONCLUSIONS: The ED(95) of remifentanil for attenuating the hypertensive response to tracheal intubation during induction of anaesthesia in severely preeclamptic patients undergoing caesarean delivery under general anaesthesia was 1.34 µg/kg.

Electrical characteristic analysis using low-frequency noise in low-temperature polysilicon thin film transistors.

This study carried out an electrical characteristic analysis using low-frequency noise (LFN) in top gate p-type low-temperature polysilicon thin film transistors (LTPS TFTs) with different active layer thicknesses between 40 nm and 80 nm. The transfer characteristic curves show that the 40-nm device has better electrical characteristics compared with the 80-nm device. The carrier number fluctuation, with and without correlated mobility fluctuation model in both devices, has modeled well the measured noise. On the other hand, the trap density and coulomb scattering in the 40-nm device are smaller compared with the 80-nm device. To confirm the effectiveness of the LFN noise analysis, the trap densities at a grain boundary are extracted using in both devices the similar methods of Proano et al. and Levinson et al. That is, coulomb scattering, caused by the trapped charges at or near the interface, has a greater effect on the device with inferior electrical properties. Based on the LFN and the quantitative analysis of the trap density at a grain boundary, the interface traps between the active layer and the gate insulator can explain the devices' electrical degradation.

Thiopental dose requirements for induction of anaesthesia and subsequent endotracheal intubation in patients with complete spinal cord injuries.

BACKGROUND: Dose requirements of thiopental depend on patient characteristics and infusion rate. We determined thiopental dose requirements for induction of anaesthesia, and the effects of remifentanil on cardiovascular and bispectral index (BIS) responses to tracheal intubation in spinal cord-injured (SCI) patients undergoing general anaesthesia. METHODS: Twenty patients with traumatic complete SCI undergoing elective surgery were enrolled. Twenty patients without SCI served as control. Anaesthesia was induced with thiopental, followed by remifentanil 1 µg/kg and rocuronium 0.8 mg/kg, and maintained with 2% sevoflurane and 50% nitrous oxide in oxygen after tracheal intubation. Thiopental was administered at a rate of 50 mg/15 s until abolition of the eyelash reflex. Thiopental doses, BIS values, systolic arterial blood pressure (SAP), heart rate (HR) and plasma catecholamine concentrations were measured. RESULTS: Total thiopental dose required to abolish the eyelash reflex based on total body weight (BW) (5.26 ± 0.87 vs. 3.91 ± 1.07 mg/kg, P < 0.001) or lean BW (6.56 ± 1.37 vs. 5.24 ± 1.36 mg/kg, P < 0.01) were significantly smaller in the SCI group than in the control. SAP was decreased by induction of anaesthesia with thiopental and remifentanil, and increased by tracheal intubation in both groups. However, the peak SAP after intubation was smaller in the SCI patients. HR increased significantly above baseline values following intubation in both groups with no significant intergroup differences. Hypertension was more frequent in the control group. Norepinephrine concentrations remained unaltered following intubation in both groups. CONCLUSIONS: These results suggest that the dose requirements of thiopental for induction of general anaesthesia and subsequent tracheal intubation are reduced in the SCI patients.

Increase of paradoxical excitement response during propofol-induced sedation in hazardous and harmful alcohol drinkers.

BACKGROUND: Paradoxical excitement response during sedation consists of loss of affective control and abnormal movements. Chronic alcohol abuse has been proposed as a predisposing factor despite lack of supporting evidence. Because alcohol and propofol have a common site of action, we postulated that paradoxical excitement responses during propofol-induced sedation occur more frequently in hazardous and harmful alcohol drinkers than in social or non-drinkers. METHODS: One hundred and ninety patients undergoing orthopaedic knee joint surgery were enrolled in this prospective and observational study. Subjects were divided into Group HD (hazardous and harmful drinkers) or Group NHD (no hazardous drinkers) according to the alcohol use disorder identification test (AUDIT). In study 1, propofol infusion was adjusted to achieve the bispectral index at 70-80 using target-controlled infusion. In study 2, the target concentration of propofol was fixed at 0.8 (study 2/Low) or 1.4 µg ml(-1) (study 2/High). Paradoxical excitement responses were categorized by intensity into mild, moderate, or severe. RESULTS: The overall incidence of paradoxical excitement response was higher in Group HD than in Group NHD in study 1 (71.4% vs 43.8%; P=0.022) and study 2/High (70.0% vs 34.5%; P=0.006) but not in study 2/Low. The incidence of moderate-to-severe response was significantly higher in Group HD of study 1 (28.6% vs 3.1%; P=0.0005) and study 2/High (23.3% vs 3.4%; P=0.029) with no difference in study 2/Low. Severe excitement response occurred only in Group HD of study 1 and study 2/High. CONCLUSIONS: Paradoxical excitement occurred more frequently and severely in hazardous and harmful alcohol drinkers than in social drinkers during propofol-induced moderate-to-deep sedation, but not during light sedation.

Dose-related attenuation of cardiovascular responses to tracheal intubation by intravenous remifentanil bolus in severe pre-eclamptic patients undergoing Caesarean delivery.

BACKGROUND: The optimal dose of remifentanil to attenuate the cardiovascular responses to tracheal intubation in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia has not been established. We compared the effects of two low doses of remifentanil on the cardiovascular responses to tracheal intubation and neonatal outcomes. METHODS: Forty-eight women with severe pre-eclampsia were randomly assigned to receive either remifentanil 0.5 µg kg⁻¹ (R0.5 group, n=24) or 1 µg kg⁻¹ (R1.0 group, n=24) over 30 s before induction of anaesthesia using thiopental 5 mg kg⁻¹ and succinylcholine 1.5 mg kg⁻¹. Systolic arterial pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were measured. Neonatal effects were assessed using Apgar scores and umbilical cord blood gas analysis. RESULTS: SAP was decreased by induction of anaesthesia and increased by tracheal intubation in both groups. The peak SAP after intubation was greater in the R0.5 group than in the R1.0 group, whereas it did not exceed baseline values in either group. HR increased significantly above baseline in both groups with no significant differences between the groups. Three subjects in the R1.0 group received ephedrine due to hypotension (SAP < 90 mm Hg). Norepinephrine concentrations remained unaltered after intubation and increased significantly at delivery with no significant differences between the groups. Neonatal Apgar scores and umbilical arterial and venous pH and blood gas values were comparable between the groups. CONCLUSIONS: Both doses of remifentanil effectively attenuated haemodynamic responses to tracheal intubation with transient neonatal respiratory depression in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia. The 1.0 µg kg⁻¹ dose was associated with hypotension in three of 24 subjects.

Relationship of statins to clinical presentation and biochemical outcomes after radical prostatectomy in Korean patients.

The aim of this study was to determine whether or not statins influence biochemical recurrence (BCR) in Korean patients undergoing surgical treatment for prostate cancer. We reviewed data from 687 men who underwent radical retropubic prostatectomy and who did not receive neoadjuvant treatment. Of these patients, 87 reported the use of preoperative statins at surgery. BCR-free survival was determined after exclusion of 78 patients with lymph node metastases and/or who received immediate adjuvant treatment. Patients on statin therapy were more likely to have a co-morbid disease (P < 0.05). Mean PSA (9.6 vs 13.6 ng ml(-1), P = 0.002) and PSA density (0.27 vs 0.38 ng ml(-1) ml(-1), P<0.001) were significantly lower in patients on statins. However, in the multivariable linear regression model, statin use was not associated with a decrease in PSA. Overall BCR for the entire cohort was not significantly different between the statin and nonstatin groups. On multivariate analysis, positive surgical margin and seminal vesicle invasion were independent risk factors for BCR-free survival, whereas other variables, including statin use, were not significant in predicting the risk of BCR. Patients with positive surgical margin and seminal vesicle invasion had a 2.1- (odds ratio, 2.15; 95% confidence interval, 1.29-3.57; P = 0.003) and 2.2-fold risk (odds ratio, 2.21; 95% confidence interval, 1.25-3.89; P = 0.006) of BCR. Preoperative statin use is not associated with reduced BCR following radical prostatectomy.

Altered cardiovascular responses to tracheal intubation in patients with complete spinal cord injury: relation to time course and affected level.

BACKGROUND: We determined cardiovascular responses to tracheal intubation in relation to the time since injury in patients with different levels of spinal cord injury. METHODS: Two hundred and fourteen patients with complete cord injury were studied. They were either quadriplegics (>C7, n=71) or paraplegics (20 yr. Twenty patients with no cord injury served as controls. Systolic arterial pressure (SAP), heart rate (HR), and plasma catecholamine concentrations were determined. RESULTS: Intubation did not affect SAP in the quadriplegics regardless of the time post-injury, but it significantly increased SAP in all paraplegics. Moreover, the pressor response was enhanced in the paraplegics who were 10 yr or more since injury (P<0.05). HR increased significantly in all groups; the magnitude of the increase was less only in acute quadriplegics compared with controls. Plasma concentrations of norepinephrine increased in every group except for the quadriplegics within 4 weeks of injury. The maximum increases in SAP, HR, and norepinephrine from awake baseline values were smaller in the quadriplegics than in the paraplegics (P<0.01). CONCLUSIONS: The cardiovascular and catecholamine responses to intubation change as a function of the time elapsed and the level of the cord injury. In this study, the pressor response to tracheal intubation was abolished in the quadriplegics but not in paraplegics; indeed, it was enhanced at 10 yr or more since injury in this group.

Fatal cerebral hemorrhage associated with autonomic hyperreflexia during surgery in the prone position in a quadriplegic patient: a case report.

Intracerebral hemorrhage is an unusual complication of autonomic hyperreflexia (AHR), which can be fatal if massive bleeding occurs with subsequent brain herniation. Episodes of AHR are most often triggered by bladder and rectal distention. We present a case of a 45-year-old quadriplegic male who suffered left basal ganglia and thalamic hemorrhage associated with AHR during surgery for pressure sore defects in the prone position under local anesthesia. Early recognition and removal of triggering factors of AHR failed to bring his blood pressure under control. The patient continued to deteriorate neurologically and died 9 days after the attack. A preventive measure rather than episodic treatment of AHR may be of paramount importance to avoid life-threatening complications, especially when a patient with a history of AHR is undergoing surgery in the prone position.

Anaesthetic requirement and stress hormone responses in patients undergoing lumbar spine surgery: anterior vs. posterior approach.

BACKGROUND: The intensity of nociceptive stimuli reflects the severity of tissue injury. The anaesthetic requirement and stress hormonal responses were determined to learn whether they differ according to different surgical approaches (anterior vs. posterior) during the spinal surgery. METHODS: Patients undergoing lumbar spine surgery without neurological deficits were divided into two groups: one having posterior (n=13) and the other having anterior fusion (n=13). The end-tidal sevoflurane concentrations (ET(SEVO)) required to maintain the bispectral index score at 40-50 were determined. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum osmolality and plasma concentrations of catecholamines, cortisol and vasopressin (AVP) were measured. RESULTS: There were no differences in MAP, HR, CVP and serum osmolality between the groups. ET(SEVO) was higher in the anterior than in the posterior group (P<0.05). The plasma concentrations of norepinephrine and cortisol increased in both groups during the surgery, whereas those of epinephrine remained unchanged. AVP concentrations increased during the surgery in the anterior group, and remained unaltered in the posterior group. The anterior group needed more analgesics (P<0.01) during the first 1 h after the operation. CONCLUSIONS: The anterior approach required a deeper level of anaesthesia while undergoing spinal surgery and more use of post-operative analgesics than the posterior approach. It was also associated with a more pronounced AVP release during the surgery.

Effects of remifentanil on cardiovascular and bispectral index responses to endotracheal intubation in severe pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia.

BACKGROUND: We examined the effects of remifentanil on cardiovascular and bispectral index (BIS) responses to tracheal intubation and neonatal outcomes in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia. METHODS: Forty-two women with severe pre-eclampsia were randomly assigned to receive either remifentanil 1 microg kg(-1) (n=21) or saline (n=21) over 30 s before induction of anaesthesia using thiopentone 4 mg kg(-1) and suxamethonium 1.5 mg kg(-1). Mean arterial pressure (MAP), heart rate (HR) and BIS values as well as plasma catecholamine concentrations were measured. Neonatal effects were assessed using Apgar scores and umbilical cord blood gas analysis. RESULTS: Induction with thiopentone caused a reduction in MAP and BIS in both remifentanil and control groups. Following the tracheal intubation MAP and HR increased in both groups, the magnitude of which was lower in the remifentanil group. BIS values also increased, of which magnitude did not differ between the groups. Norepinephrine concentrations increased significantly following the intubation in the control, while remained unaltered in the remifentanil group. The neonatal Apgar scores at 1 min were significantly lower in the remifentanil group than in the control. However, Apgar scores at 5 min, and umbilical artery and vein blood gas values were similar between the groups. CONCLUSIONS: These results suggest that a single bolus of 1 microg kg(-1) remifentanil effectively attenuates haemodynamic but not BIS responses to tracheal intubation in pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia. However, its use was associated with maternal hypotension and neonatal respiratory depression requiring resuscitation.

Cardiovascular and arousal responses to laryngoscopy and tracheal intubation in patients with complete spinal cord injury.

BACKGROUND: We aimed to determine whether the autonomic and arousal responses to laryngoscopy and tracheal intubation were altered in patients with spinal cord injury (SCI). METHODS: One hundred and sixteen patients with traumatic complete SCI were grouped according to the time elapsed after the injury (<3 days and >9 months) and the level of injury (above T5 and below T5): acute high (AH, n=25), chronic high (CH, n=26), acute low (AL, n=20), and chronic low (CL, n=45). Twenty-five patients without SCI served as a control group. Bispectral index (BIS) response, systolic arterial pressure (SAP), heart rate (HR), and plasma concentrations of catecholamines and arginine vasopressin were measured. RESULTS: Both CH and CL groups showed a greater reduction in BIS values after induction of anaesthesia with thiopental compared with controls (P<0.05). However, BIS values after intubation increased similarly in all groups from the value measured just before laryngoscopy. SAP increased in the AL and CL and control groups but not in the AH and CH groups. HR increased significantly in all groups; though to a lesser degree in the AH compared with the other groups. Plasma norepinephrine concentrations increased in all except the AH group, but vasopressin concentrations were unchanged. CONCLUSIONS: The arousal response to laryngoscopy and tracheal intubation as measured by BIS is not altered in SCI, but cardiovascular and catecholamine responses may be changed depending on time elapsed and the level of the injury. However, an identical dose of thiopental may reduce BIS value after intubation more profoundly in patients with chronic SCI.

Expression of nitric oxide synthase isoforms in the testes of pigs.

This study examined the expression of three isoforms of nitric oxide synthase (NOS) in the testes of pigs. Immunohistochemical studies demonstrated the presence of nNOS, eNOS and iNOS in interstitial cells, primary spermatocytes and spermatids. Positive immunoreactions for eNOS and iNOS were detected in peritubular myoid cells. Some vascular endothelial cells were positive for nNOS and eNOS. The expression of nitrotyrosine was detected in interstitial cells. In addition, the histochemical study revealed that all the interstitial cells were stained positively for NADPH-diaphorase, although some spermatids and vascular endothelial cells displayed moderate enzymatic activity. These findings suggest that three isoforms of NOS are expressed in the testis of pig and that they play important roles in the biology of interstitial cells that produce testosterone, as well as in spermatogenesis in the seminiferous tubules.

Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT-PCR.

BACKGROUND: A small subgroup of atopic dermatitis (AD) patients with normal serum IgE levels and without specific IgE sensitization has been termed 'intrinsic type of AD' (ADi) as a counterpart to the term 'extrinsic type of AD' (ADe). However, there are neither molecular markers nor clinically diagnostic tools for distinguishing between ADi and ADe. OBJECTIVE: The present studies were undertaken to clarify the pathogenesis and in vivo cytokine micromilieu of ADi patients in comparison with ADe patients. METHODS: We used semiquantitative RT-PCR to investigate the expression of various cytokines and assessed the tissue eosinophil counts in skin biopsies from both types of AD patients. RESULTS: Although there was no significant difference of cellular infiltrates in the lesional skin between ADe and ADi patients, ADe had significantly increased tissue eosinophilia than ADi. Based on our RT-PCR, the expression patterns of cytokines could be categorized into four groups. The first group includes IL-5, IL-13, and IL-1beta, whose levels of mRNA expression were higher in both types of AD patients than non-atopic (NA) subjects, while ADe patients had even higher levels than ADi patients. The second group includes interferon-gamma (IFN-gamma), IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-10, whose levels of mRNA expression were elevated in both types of AD patients without differences between ADe and ADi patients. The third group includes tumour necrosis factor-alpha (TNF-alpha), whose mRNA expression was more decreased in both types of AD patients than NA, and the fourth group includes IL-6 and transforming growth factor-beta (TGF-beta), which did not show any differences among the three groups. CONCLUSION: These current data demonstrate that the expressions of cytokines IL-5, IL-13, and IL-1beta mRNA and the number of dermal infiltrating eosinophils are increased in ADe patients compared with ADi patients.

Effect of botulinum toxin A chemodenervation in sensory strabismus.

PURPOSE: To study the effect of botulinum toxin type A chemodenervation in sensory strabismus. METHODS: Twelve patients with sensory strabismus were treated with an injection of botulinum toxin type A (Botox; Allergan, Irvine, Calif). Botulinum toxin type A was diluted with 0.9% sodium chloride without preservative at a dose that ranged from 1.25-5 U. A Teflon-coated needle electrode was inserted into the medial rectus muscle in cases of esotropia and into the lateral rectus muscle in cases of exotropia. Four patients were treated with > or =2 injections of botulinum toxin type A. Changes in the angle of strabismus and related complications were followed for >6 months postinjection. RESULTS: The mean deviation before injection was 33.8 prism diopters (delta) and the mean corrective effect on the deviation was 72.8% after injection in patients with sensory strabismus. The final deviation in 9 patients was <10 delta. Complications were hypertropia in 3 (25%) patients and conjunctival hemorrhage in 1 (8.3%) patient. CONCLUSION: Botulinum toxin type A is likely to prevent muscle contracture and affect muscle and neuronal tissues. This study on the effects of sensory strabismus with botulinum toxin type A injection suggests it has the potential to replace surgery or be used as an adjuvant therapy.