CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population

Genetic differences in the metabolism of xenobiotics have recently been suggested as modifiers of individual susceptibility to bladder cancer (BC). The objective of this study was to investigate the relationship between bladder tumor and variants of cytochrome p450 1A2 (CYP1A2) 734 C → A, cytochrome p450 2D6 (CYP2D6) 1934 G → A, glutathione S-transferase M1, (GSTM1 null), glutathione S-transferase T1 (GSTT1 null), and glutathione S-transferase P1 (GSTP1) I105 V. We investigated the distribution of these polymorphisms in 135 BC patients and in 128 age and sex-matched cancer-free controls. The polymorphisms were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and the multiplex PCR method. Genotype and allele frequencies and their associations with BC risk, demographic factors, smoking status, and tumor stage were investigated. The prevalence of GSTT1 null genotype in cases was 23%, compared with 7% in the control group (OR = 3.94, 95% CI = 1.70–9.38, P = 0.001). There was no association between the studied polymorphisms of CYP1A2, CYP2D6, GSTM1, and GSTP1 genes and BC. There was an association between smoking status and BC. These data seem to indicate that GSTT1 gene polymorphism may be associated with BC in the Turkish population studied. Further studies will be needed to clarify the role of such variation in determining susceptibility to BC.     

TGFB1 gene polymorphism Leu10Pro (c.29T>C), prostate cancer incidence and quality of life in patients treated with brachytherapy

Objectives  Transforming growth factor beta1 gene (TGFB1) variant Leu10Pro (L10P) has previously been implicated in prostate cancer risk and radiation-induced side-effects. We investigated whether prevalence of this polymorphism is increased in prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. Methods  A series of 445 consecutive patients treated for early-stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between 10/2000 and 10/2007 at our institution and a comparison group of 457 healthy male control individuals were screened for TGFB1 L10P (869T>C) polymorphism. Morbidity was assessed prospectively and compared between carriers versus non-carriers using International Prostate Symptom Score (IPSS), disease-specific Quality-of-Life single question added to the IPSS and International Index of Erectile Function with its subgroups. Results  The Leu/Leu genotype was found in 150 patients (34%) versus 180 controls (39%), the Pro/Pro genotype in 75 patients (17%) versus 65 controls (14%) and the Leu/Pro genotype in 220 patients (49%) versus 212 controls (46%) without any statistically significant differences between the two groups. There was a trend towards an increased prevalence of the L10P substitution among patients with a per allele odds ratio of 1.19 (95% CI 0.99–1.44; P = 0.08). After a median follow-up of 18 months (range 1–60 months) there were no statistically significant differences regarding morbidity. Conclusions   TGFB1 polymorphism L10P is not strongly associated with prostate cancer risk. After 18 months, there was no evidence for increased adverse radiotherapy responses in heterozygote or rare homozygote carriers. Longer follow-up may be necessary to detect a statistically significant difference.     

RETRACTED ARTICLE: Prophylactic antiemetic therapy with droperidol in patients undergoing laparoscopic cholecystectomy

Purpose. The incidence of postoperative nausea and vomiting (PONV) following laparoscopic cholecystectomy (LC) is relatively high when no prophylactic antiemetic is given. We have studied the efficacy of a commonly used and well-established antiemetic, droperidol, for the prevention of PONV in patients undergoing LC. Methods. In a randomized, double-blind, placebo-controlled study, 60 patients received placebo (saline) or droperidol 50 μg·kg⁻¹ (maximum dose, 2.5 mg) intravenously immediately before the induction of anesthesia (n = 30 of each). A standard general anesthetic technique was employed throughout. Results. A complete response, defined as no PONV and no need for another rescue antiemetic medication during the first 24 h after anesthesia, was 57% and 83% in patients who had received placebo and droperidol 50 μg·kg⁻¹, respectively (P < 0.05). No clinically serious adverse events were observed in any of the groups. Conclusion. Prophylactic antiemetic therapy with droperidol 50 μg·kg⁻¹ (maximum dose, 2.5 mg) is highly effective for preventing PONV after LC. Received for publication on August 3, 1998; accepted on February 23, 1999     

Intra-articular injection versus interscalene brachial plexus block for acute-phase postoperative pain management after arthroscopic shoulder surgery

BackgroundThe minimally invasive approach of arthroscopic shoulder surgery is beneficial; however, for optimal outcomes, perioperative pain management is essential. This cross-sectional study aimed to examine the analgesic effectiveness of intra-articular injection (IA) versus interscalene brachial plexus block (ISPB) among patients treated with arthroscopic shoulder surgeries.MethodsWe reviewed 100 consecutive patients who underwent shoulder arthroscopic surgery, of whom 50 each underwent IA (February 2019─January 2020; IA group) and ISPB (October 2018─July 2019; ISPB group). The primary outcome was the postoperative pain score measured using a Wong–Baker FACES Pain Rating Scale preoperatively and at 2, 6, 12, 24, and 48 h postoperatively. We performed multiple regression analysis to examine whether IA/ISPB selection is associated with acute-phase postoperative pain and adjusted for intra-articular injection, interscalene brachial plexus block, postoperative pain management, arthroscopic shoulder surgery, IA with 10 mg of morphine previously reported prognostic factors for postoperative pain (e.g., surgical procedures, operative time, older age, and preoperative pain). Furthermore, we examined induction time, total pentazocine dosage, and total postoperative nausea and vomiting (PONV) events.ResultsThere were no significant differences between the IA and ISPB groups in perioperative pain control during the acute-phase periods (p = 0.12, repeated analysis of variance). The difference in anesthesia method was not a prognostic factor for acute-phase postoperative pain (p = 0.11). The IA group (15.06 ± 4.00 min) had a significantly shorter mean anesthesia induction time than the ISPB group (29.23 ± 9.22 min) (p = 0.0001). There was no significant between-group difference in the total pentazocine dosage during the first 7 days (p = 0.3934) postoperatively. PONV was observed in eight (17.0%) and two (4.2%) patients in the IA and ISPB groups, respectively. There was no significant between-group difference in the PONV incidence (p = 0.1582).ConclusionsThere was no significant difference in acute-phase postoperative pain management between the IA and ISPB groups. The induction time was significantly shorter in IA.IRBApproval number: UOEHCRB20-078, IRB approval date: September 9th, 2020; study duration: October 2018 to January 2020.     

Comparison of dexamethasone,metoclopramide, and their combination in the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy

Background Postoperative nausea and vomiting (PONV) are one of the most common complaints following anesthesia and surgery. This study was designed to evaluate the efficacy of dexamethasone, metoclopramide, and their combination to prevent PONV in patients undergoing laparoscopic cholecystectomy. Methods A total of 160 ASA physical status I and II patients were included in this randomized, double blind, placebo-controlled study. Patients were randomly assigned to 4 groups (n = 40 each): group 1 consisting of control patients administered 0.9% NaCl; group 2 patients received metoclopramide 10 mg just before the end of anesthesia; group 3 patients received dexamethasone 8 mg after the induction of anesthesia; and group 4 patients received dexamethasone 8 mg after the induction of anesthesia and metoclopramide 10 mg before the end of anesthesia. The incidence of PONV, mean visual analog pain scores at rest and on movement, time to the first request for analgesia, side effects, and well-being score were recorded during the first 24 h postoperatively. Results Data were analyzed using one-way analysis of variance (ANOVA) and the χ² test, with p < 0.05 considered statistically significant. The total incidence of PONV was 60% with placebo, 45% with metoclopramide, 23% with dexamethasone, and 13% with the combination of dexamethasone plus metoclopramide. None of the dexamethasone plus metoclopramide group patients (p < 0.05 versus groups 1 and 2) and one dexamethasone group patient (p < 0.05 versus group 1) required antiemetic rescue, as compared with four patients in the metoclopramide group and six patients in the placebo group. Pain scores, the time to the first request for analgesia, and side effects were similar across the study groups. Conclusions Dexamethasone and the combination of dexamethasone plus metoclopramide were more effective in preventing PONV than metoclopramide and placebo.     

The R229Q mutation in <Emphasis Type="Italic">NPHS2</Emphasis> may predispose to proteinuria in thin-basement-membrane nephropathy

Thin-basement-membrane nephropathy (TBMN) is characterized by persistent dysmorphic hematuria, and the presence of proteinuria is a risk factor for renal impairment. TBMN is often due to mutations in the COL4A3 and COL4A4 genes, and this study determined whether additional mutations in genes encoding other structures in the glomerular filtration barrier contributed to the development of proteinuria. Fifty-six unrelated individuals with TBMN including 18 (32%) with proteinuria ≥ 300 mg/L and ten (18%) with proteinuria ≥ 500 mg/L were studied. Deoxyribonucleic acid (DNA) was screened for NPHS2 mutations and variants (R138Q and P375L) using single-stranded conformational analysis (SSCA) and for the R229Q mutation by sequencing. DNA was also screened for ACTN4 mutations. R229Q was more common in patients with TBMN and proteinuria ≥ 500 mg/L (p < 0.05), and a possible NPHS2 mutation (671G>A, R224H) was identified in one patient with proteinuria 700 mg/L. No other NPHS2 variants correlated with proteinuria, and no ACTN4 mutations were found. Individuals with TBMN and R229Q are carriers of the autosomal recessive forms of both Alport syndrome and familial focal segmental glomerulosclerosis (FSGS). The early demonstration of R229Q in individuals with TBMN may indicate those at increased risk of proteinuria and renal impairment.     

Lack of death receptor 4 (<Emphasis Type="Italic">DR4</Emphasis>) expression through gene promoter methylation in gastric carcinoma

Background and aims  To determine the underlying mechanism for the differential expression, the extent of promoter methylation in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-related genes acting downstream of TRAIL was examined in early and advanced gastric carcinomas. Methods  The extent of promoter methylation in the DR4, DR5, DcR1, DcR2, and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase chain reaction. Results  The promoters for DcR1, DcR2, and CASP8 were largely unmethylated in early gastric carcinoma, advanced gastric carcinoma, and controls, with no significant difference among them. Protein levels of DR4, DcR1, and DcR2 as revealed by immunohistochemistry correlated with the extent of the respective promoter methylation (P < 0.05 in all cases). Hypomethylation, rather than hypermethylation, of the DR4 promoter was noted in invasive gastric malignancies, with statistical significance (P = 0.003). Conclusion  The promoter methylation status of TRAIL receptors in gastric carcinoma may have clinical implications for improving therapeutic strategies in patients with gastric carcinoma.     

Genotype–phenotype correlation in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) and PKD1 mutations have a more severe disease than do patients with PKD2 mutations. The aim of this study was to compare phenotypes between children with mutations in the PKD1/PKD2 genes. Fifty PKD1 children and ten PKD2 children were investigated. Their mean age was similar (8.6 ± 5.4 years and 8.9 ± 5.6 years). Renal ultrasound was performed, and office blood pressure (BP), ambulatory BP, creatinine clearance and proteinuria were measured. The PKD1 children had, in comparison with those with PKD2, significantly greater total of renal cysts (13.3 ± 12.5 vs 3.0 ± 2.1, P = 0.004), larger kidneys [right/left kidney length 0.89 ± 1.22 standard deviation score (SDS) vs 0.17 ± 1.03 SDS, P = 0.045, and 1.19 ± 1.42 SDS vs 0.12 ± 1.09 SDS, P = 0.014, successively] and higher ambulatory day-time and night-time systolic BP (day-time/night-time BP index 0.93 ± 0.10 vs 0.86 ± 0.05, P = 0.021 and 0.94 ± 0.07 vs 0.89 ± 0.04, P = 0.037, successively). There were no significant differences in office BP, creatinine clearance or proteinuria. Prenatal renal cysts (14%), hypertension defined by ambulatory BP (27%) and enlarged kidneys (32%) were observed only in the PKD1 children. This is the first study on genotype–phenotype correlation in children with ADPKD. PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1.     

<Emphasis Type="Italic">IL-10</Emphasis> −1082 G>A: a risk for prostate cancer but may be protective against progression of prostate cancer in North Indian cohort

Background  Chronic intraprostatic inflammation is suspected to play a major role in the pathogenesis of prostate cancer (PCa). Polymorphisms in interleukin-10 (IL-10), a key anti-inflammatory cytokine gene can influence immune response and immune evasion of tumor cells. Its role as an anti-metastatic molecule is also well documented. Methods  Gene promoter polymorphisms in IL-10 (−1082 G>A and −819 C>T) was analyzed in 159 PCa patients and 259 healthy controls to investigate their potential association with susceptibility for PCa. Results  Our results indicated that the heterozygous (GA) and homozygous mutant (AA) genotypes of IL-10 −1082 to be more prevalent among PCa patients in comparison to controls (GA: OR − 2.8, p = 0.011; AA: OR − 2.3, p = 0.037). More patients (92.5%) than controls (82.7%) were positive for the A allele (GA + AA: OR − 2.6, p = 0.015). We observed lower frequency of T(−819)-G(−1082) haplotype in patients without bone metastasis (4.4%, OR − 0.30, p = 0.019) in comparison to PCa patients with bone metastasis (12.6%). Conclusion  Our results support the emerging hypothesis that genetically determined immune activity may play a role in the pathophysiology of PCa. Our findings of high producer of IL-10 −1082 variants suggest initiation of PCa. Future studies in large cohort of different ethnicity PCa groups are warranted to establish definite associations with other cytokine gene polymorphisms.     

Dose of intraoperative remifentanil administration is independently associated with increase in the risk of postoperative nausea and vomiting in elective mastectomy under general anesthesia

BackgroundPostoperative nausea and vomiting (PONV) is one of the common complications in patients who have undergone surgery with general anesthesia. The association of intraoperative use of remifentanil with PONV has remained controversial. The aim of the current study was to determine the association of dose of intraoperative remifentanil administration with incidence of PONV.MethodsThe present study was a single-center retrospective observational study and included 423 female patients with American Society of Anesthesiologists physical status I or II who underwent elective mastectomy under general anesthesia between October 2011 and October 2012. The incidence of PONV within 3 days after the operation was prospectively assessed. The time-weighted average of remifentanil during the operation (twRem) was calculated. We used a multivariate regression model to assess the independent association of the twRem with the incidence of PONV.ResultsAmong 423 patients, 129 patients (30.5%) had PONV during the study period. Remifentanil was administrated in 355 patients (83.9%). In the multivariate logistic regression model using categories of twRem, we found that increased twRem was independently associated with increase in the risk of PONV (P = .01). There was an independent association between twRem greater than 0.2 μg/kg per minute and increase in the risk of PONV.ConclusionThis retrospective observational study revealed a dose-dependent association between dose of intraoperative remifentanil administration and increase in the risk of PONV. Time-weighted average of remifentanil greater than 0.2 μg/kg per minute was independently associated with risk of PONV.     

Clinical and genetic factors associated with post-operative nausea and vomiting after propofol anaesthesia

Background

The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model.

Methods

This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2–24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes.

Results

The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0–2 h and 23% at 2–24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post-anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71–0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10⁻⁵). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028).

Conclusions

Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D₂ receptors in PONV.     

<Emphasis Type="Italic">LRP5</Emphasis> Polymorphisms and Response to Risedronate Treatment in Osteoporotic Men

Genetic factors are important in the pathogenesis of osteoporosis, but little is known about the genetic determinants of treatment response. Previous studies have shown that polymorphisms of the LRP5 gene are associated with bone mineral density (BMD), but the relationship between LRP5 polymorphisms and response to bisphosphonate treatment in osteoporosis has not been studied. In this study we investigated LRP5 polymorphisms in relation to treatment response in a group of 249 osteoporotic or osteopenic men who participated in a 24-month randomized double blind placebo-controlled trial of risedronate treatment. BMD and biochemical markers of bone turnover were measured at baseline and after 6, 12, and 24 months of follow-up. We analyzed two coding polymorphisms of LRP5, which have previously been associated with BMD, V667M (rs4988321) and A1330V (rs3736228), and found a significant association between the A1330V polymorphism and hip BMD at baseline. Subjects with the 1330 Val/Val genotype had 8.4% higher total-hip BMD compared with the other genotype groups (P = 0.009), and similar associations were observed at the femoral neck (P = 0.01) and trochanter (P = 0.002). There was no association between A1330V and spine BMD, however, or between the V667M polymorphism and BMD at any site. The difference in hip BMD between A1330V genotype groups remained significant throughout the study, but there was no evidence of a genotype–treatment interaction in either risedronate- or placebo-treated patients. In conclusion, the LRP5 A1330V polymorphism is associated with hip BMD in osteoporotic men, but allelic variations in LRP5 do not appear to be associated with response to bisphosphonate treatment.     

The impact of crystalloid versus colloid fluids on postoperative nausea and vomiting: A systematic review and meta-analysis of randomized controlled trials

Study objectiveEvidence suggests that administering appropriate volumes of perioperative fluid replacement therapies can decrease the incidence of postoperative nausea and vomiting (PONV). However, the relative effects of colloids and crystalloids on PONV are still unclear. The objective of this systematic review was to determine whether administering colloids to adults undergoing noncardiac surgery significantly reduces PONV incidence and rescue antiemetic use, compared with administering crystalloids.DesignThis study has been registered in PROSPERO (ID: CRD42016036174). We performed a meta-analysis of randomized controlled trials that compared the incidence of PONV and rescue antiemetic use in surgical patients randomized to receive colloid or crystalloid fluids. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was explored through I² statistics.PatientsNine randomized trials that included a total of 843 surgical patients met the inclusion criteria.MeasurementsThe primary outcome of interest was the incidence of overall PONV. Secondary outcomes included the incidence of postoperative nausea (PON), postoperative vomiting (POV), and rescue antiemetic use.Main resultsCompared with crystalloid fluids, perioperative colloid administration did not reduce the incidence of overall PONV (RR 0.802; 95% CI: 0.561, 1.145; I² = 57.168%). However, the colloid infusion group (RR 0.625; 95% CI: 0.440, 0.888) had reduced PONV compared with the crystalloid infusion group (RR 1.244; 95% CI: 0.742, 2.085), in the subgroup with anesthesia duration >3 h and who underwent major surgery. Meta-regression analysis also showed that the slope was significant (p = 0.04215) for duration of anesthesia.ConclusionsColloid administration reduced the incidence of PONV in adults undergoing elective, noncardiac, major surgery under general anesthesia for >3 h. However, clinical studies performed in larger cohorts are required to determine the impact of colloids on PONV.     

Contribution of a Common Variant in the Promoter of the 1-α-Hydroxylase Gene (<Emphasis Type="Italic">CYP27B1</Emphasis>) to Fracture Risk in the Elderly

CYP27B1 encodes mitochondrial 1α-hydroxylase, which converts 25-hydroxyvitamin D to its active 1,25-dihydroxylated metabolite. We tested the hypothesis that common variants in the CYP27B1 promoter are associated with fracture risk. The study was designed as a population-based genetic association study, which involved 153 men and 596 women aged 65–101 years, who had been followed for 2.2 years (range 0.1–5.5) between 1999 and 2006. During the follow-up period, the incidence of fragility fractures was ascertained. Bone ultrasound attenuation (BUA) was measured in all individuals, as were serum 25-hydroxyvitamin D and PTH concentrations; 86% subjects had vitamin D insufficiency. Genotypes were determined for the –1260C>A (rs10877012) and +2838T>C (rs4646536) CYP27B1 polymorphisms. A reporter gene assay was used to assess functional expression of the –1260C>A CYP27B1 variants. The association between genotypes and fracture risk was analyzed by Cox’s proportional hazards model. We found that genotypic distribution of CYP27B1 –1260 and CYP27B1 +2838 polymorphisms was consistent with the Hardy-Weinberg equilibrium law. The two polymorphisms were in high linkage disequilibrium, with D′ = 0.96 and r ² = 0.94. Each C allele of the CYP27B1 –1260 polymorphism was associated with increased risk of fracture (hazard ratio = 1.34, 95% CI 1.03–1.73), after adjustment for age, sex, number of falls, and BUA. In transient transfection studies, a reporter gene downstream of the –1260(A)-containing promoter was more highly expressed than that containing the C allele. These data suggest that a common but functional variation within the CYP27B1 promoter gene is associated with fracture risk in the elderly.     

Effect of intraoperative subhypnotic infusion of propofol on postoperative nausea and vomiting: A retrospective analysis

Study objectiveTo measure the possible association between subhypnotic propofol infusion during general balanced anesthesia and the incidence of PONV.DesignRetrospective Cohort Analysis Using Propensity Score Matching.SettingPostanesthesia care unit and inpatient unit.PatientsPatients with American Society of Anesthesiologists (ASA) physical status I-IV, undergoing non-cardiac surgery lasting >2 h were included. Patients were excluded if transferred to the intensive care unit after surgery or received ketamine. Initially 70,976 patients were screened, and a cohort of 51,707 eligible adult patients undergoing non-cardiac surgery under general balanced anesthesia between 2015 and 2019 were included. Using a propensity score matching, 3185 patients who received subhypnotic propofol during general balanced anesthesia were matched with 5826 patients who did not receive subhypnotic propofol in a 1:2 ratio.InterventionsNone.MeasurementsThe primary outcome was the incidence of PONV during PACU stay. The secondary outcome was the incidence of PONV within the first 24 h after surgery. Exploratory outcomes were time-to-extubation and length of hospital stay.Main resultsA total of 9011 patients were included (3185 patients who received propofol infusion, and 5826 patients who did not receive propofol infusion) after propensity score matching. The adjusted odds ratio for PONV incidence was 1.03 (95% CI: 0.90, 1.18; p = 0.635) in PACU, and 1.05 (95% CI: 0.90, 1.23; P = 0.50) within 24 h after surgery. The length of hospital stay was 6 h shorter (ratio of means (95% CI) of 0.92, 0.89, 0.94), p < 0.001) and time-to-extubation was 2 min longer (ratio of means 1.24 (1.20, 1.28), p < 0.001) in patients receiving subhypnotic propofol infusion.ConclusionsOur study suggests that subhypnotic propofol infusion during general balanced anesthesia is not associated with a reduction in the incidence of PONV during PACU stay and within the first 24 h after surgery. However, it is associated with decreased LOS and increased time-to-extubation, but differences in neither outcome were clinically important.     

Polymorphisms in the Hypoxia Inducible Factor 1-α and the Impact on the Prognosis of Early Stages of Oral Cancer

Background  Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular responses to hypoxia and presumably plays a central role in the control of tumor growth. Polymorphisms or mutations increasing its activity and stability in vitro under normoxia have recently been identified. In this study, we aimed to investigate the effect of C1772T and G1790A single nucleotide polymorphisms (SNPs), located within the exon 12 of HIF-1α on the prognosis of early stages of oral squamous cell carcinoma (OSCC). Methods  The frequency of C1772T and G1790A polymorphisms was determined by PCR-RFLP in 139 DNA samples from healthy volunteers and 74 patients with surgically treated T1/2 N0 OSCC. The impact of HIF-1α SNPs on tumor size, invasive depth, pathological features, and histological grade was studied. Correlations between genotype and relapse and/or disease-specific survival were evaluated by Kaplan-Meier analysis and log-rank test. Results  Concerning G1790A SNP, the frequencies of GA heterozygous and AA variant homozygous genotypes were significantly higher in patients than in healthy volunteers (32.8% vs. 6.5% and 4.7% vs. none, respectively) (P < .0001). Also, the presence of the variant allele A was associated to disease-relapse (P = .02) and shorter disease-free survival (P = .04). The genotype distribution of C1772T did not diverge between patients and healthy subjects, and no differences were observed with respect to disease-free or overall survival. Conclusions  Our results suggest that G1790A polymorphism in the HIF-1α gene might confer susceptibility to OSCC and could be a marker of disfavorable prognosis at early stages.     

The effect of oral and IV ramosetron on postoperative nausea and vomiting in patients undergoing gynecological laparoscopy with total intravenous anesthesia

Purpose  Ramosetron can be administered orally as well as intravenously. We investigated the effect of oral ramosetron on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopy. Methods  One hundred and twenty women were allocated randomly to one of three groups (n = 40 in each) to receive saline (control), 0.1 mg oral ramosetron (PO), or 0.3 mg IV ramosetron (IV). Total intravenous anesthesia (TIVA) with propofol and remifentanil was used in all patients. Results  The incidence of complete response (no PONV, no rescue) in the control, IV, and PO groups was: 65%, 90%, and 87.5%, respectively, during the first 1 h; and 67.5%, 87.5%, and 80%, respectively, during 1 to 24 h. Conclusion  The effect of oral ramosetron 0.1 mg was comparable to that of IV ramosetron 0.3 mg on the prevention of PONV in women undergoing gynecological laparoscopy with TIVA. Both the oral and IV forms were effective at preventing PONV during the first 1 h after surgery.     

Postoperative nausea and vomiting prophylaxis: The efficacy of a novel antiemetic drug (palonosetron) combined with dexamethasone

BackgroundPalonosetron is a new, potent, and long-acting 5HT3-receptors antagonist that had been approved by the FDA for use in postoperative nausea and vomiting (PONV) prophylaxis. This study is designed to evaluate its efficacy combined with dexamethasone in PONV prophylaxis in highrisk patients scheduled for laparoscopic surgeries.MethodsIn this double-blind, active-controlled study, 150 patients aged 20–55 years, ASA I–II, and with Apfel’s PONV score 2–4 were equally randomized to receive dexamethasone 8 mg before anesthesia induction and saline 30 min before the end of surgery (group D + S), dexamethasone 8 mg before anesthesia induction and metoclopramide 25 mg 30 min before the end of surgery (group D + M), or dexamethasone 8 mg combined with palonosetron 0.075 mg before anesthesia induction and saline 30 min before the end of surgery (group D + P). Incidences of early and late PONV, complete response, adverse events from antiemetics used, and overall patients’ satisfaction were recorded.ResultsThe incidence of PONV was comparable in the three groups 0–6 h postoperatively. Palonosetron–dexamethasone and dexamethasone–metoclopramide combination therapies significantly reduced the incidence of PONV at 6–12 h postoperatively compared to dexamethasone monotherapy (12% and 16%, vs. 36%, respectively, with P < 0.05). Moreover, palonosetron–dexamethasone combination therapy significantly reduced the incidence of PONV at 12–24 h postoperatively compared to both dexamethasone monotherapy (16% vs. 48%, P < 0.01), and dexamethasone–metoclopramide combination therapy (16% vs. 40%, P < 0.05). The incidence of adverse drug effects was comparable in the three groups. The overall patients’ satisfaction was significantly higher in palonosetron–dexamethasone combination therapy compared to other groups.ConclusionPalonosetron–dexamethasone combination is effective and safe in PONV (early and late) prophylaxis in high-risk patients undergoing laparoscopic surgeries with known high-risk of PONV.     

Vitamin D receptor gene polymorphisms in patients with urolithiasis

Urolithiasis is a multifactorial disease, the onset and severity of which is influenced by both genetic and environmental factors. This study represents an investigation of the role of vitamin D receptor (VDR) gene polymorphisms (ApaI, BsmI, and TaqI) and combined genotypes in urolithiasis in a Turkish population. We studied 110 patients with urinary stones and 150 control subjects. The polymorphic regions were amplified using polymerase chain reaction, followed by digestion with restriction enzymes BsmI, ApaI, and TaqI, and analyzed electrophoretically. Genotype and allele frequencies were calculated, and the association with urolithiasis, family history, and recurrence of stone was investigated. Our data provide no evidence for an association between urolithiasis and VDR ApaI, BsmI, and TaqI genotypes. We also analyzed the effects of VDR ApaI, BsmI, and TaqI genotypes in combination; the “GTT” VDR haplotype, constructed from three adjacent restriction fragment length polymorphisms was overrepresented among the urolithiasis patients. However, no significant differences between heterozygous carriers (OR 1.302; 95% CI 0.527–3.215) and homozygous carriers (OR 3.39; 95% CI 0.719–15.985) were observed in our study population. A significant association was found only between the ApaI polymorphism and family history (P=0.017; χ ²=5.657). Our data indicate that the VDR ApaI, BsmI, and TaqI polymorphisms do not confer a significant risk for urolithiasis.     

Klotho Gene Polymorphisms are Associated with Osteocalcin Levels but not Bone Density of Aged Postmenopausal Women

Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization—Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c.1775G>A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c>t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G>A SNP site and a haplotype including this are associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of “rescue” by other genetic or environmental factors in this population.