Comparative study on determination of plasma thyroid hormones by chemiluminescence and electrochemiluminescence immunoassay methods in sheep

The aim of this study was to compare plasma thyroid hormone concentrations by both chemiluminescence (CLIA) and electrochemiluminescence immunoassay (ECLIA) methods in sheep. Blood samples were taken from the jugular vein of 25 clinically healthy, non-pregnant adult ewes. The plasma was analyzed to determine thyroxine (T₄), tri-iodothyronine (T₃), free thyroxine (fT₄) and free tri-iodothyronine (fT₃) concentrations. The data from this study indicates, there were significant differences in the T₄ (P < 0.0001), T₃(P < 0.01) and fT₃(P < 0.01) concentrations between the two methods, and the levels of these hormones were higher when using the ECLIA method. In determining thyroid hormones using the CLIA and ECLIA methods, significant positive correlations were found between T₄ and fT₄ (P < 0.001, r = 0.703; P < 0.0001, r = 0.806) also between T₃ and fT₃ (P < 0.0001, r = 0.922; P < 0.0001, r = 0.923) concentrations, respectively. The linear regression analysis of these hormones showed that the CLIA and ECLIA results were significantly correlated (T₄ (P < 0.01, r = 0.583), T₃ (P < 0.0001, r = 0.898), fT4 (P < 0.0001, r = 0.796) and fT₃ (P < 0.0001, r = 0.898).     

Neuromuscular adaptation during prolonged strength training, detraining and re-strength-training in middle-aged and elderly people

Effects of a 24-week strength training performed twice weekly (24 ST) (combined with explosive exercises) followed by either a 3-week detraining (3 DT) and a 21-week re-strength-training (21 RST) (experiment A) or by a 24-week detraining (24 DT) (experiment B) on neural activation of the agonist and antagonist leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris, maximal isometric and one repetition maximum (1-RM) strength and jumping (J) and walking (W) performances were examined. A group of middle-aged (M, 37–44 years, n=12) and elderly (E, 62–77, n=10) and another group of M (35–45, n=7) and E (63–78, n=7) served as subjects. In experiment A, the 1-RM increased substantially during 24 ST in M (27%, P < 0.001) and E (29%, P < 0.001) and in experiment B in M (29%, P < 0.001) and E (23%, P < 0.01). During 21 RST the 1-RM was increased by 5% at week 48 (P < 0.01) in M and 3% at week 41 in E (n.s., but P < 0.05 at week 34). In experiment A the integrated electromyogram (IEMG) of the vastus muscles in the 1-RM increased during 24 ST in both M (P < 0.05) and E (P < 0.001) and during 21 RST in M for the right (P < 0.05) and in E for both legs (P < 0.05). The biceps femoris co-activation during the 1-RM leg extension decreased during the first 8-week training in M (from 29 ± 5% to 25 ± 3%, n.s.) and especially in E (from 41 ± 11% to 32 ± 9%, P < 0.05). The CSA increased by 7% in M (P < 0.05) and by 7% in E (P < 0.001), and by 7% (n.s.) in M and by 3% in E (n.s.) during 24 ST periods. Increases of 18% (P < 0.001) and 12% (P < 0.05) in M and 22% (P < 0.001) and 26% (P < 0.05) in E occurred in J. W speed increased (P < 0.05) in both age groups. The only decrease during 3 DT was in maximal isometric force in M by 6% (P < 0.05) and by 4% (n.s.) in E. During 24 DT the CSA decreased in both age groups (P < 0.01), the 1-RM decreased by 6% (P < 0.05) in M and by 4% (P < 0.05) in E and isometric force by 12% (P < 0.001) in M and by 9% (P < 0.05) in E, respectively, while J and W remained unaltered. The strength gains were accompanied by increased maximal voluntary neural activation of the agonists in both age groups with reduced antagonist co-activation in the elderly during the initial training phases. Neural adaptation seemed to play a greater role than muscle hypertrophy. Short-term detraining led to only minor changes, while prolonged detraining resulted in muscle atrophy and decreased voluntary strength, but explosive jumping and walking actions in both age groups appeared to remain elevated for quite a long time by compensatory types of physical activities when performed on a regular basis. Accepted: 2 May 2000     

Proinflammatory Cytokine Gene Polymorphisms among Iranian Patients with Asthma

Introduction  Asthma is one of the most common respiratory diseases caused by acute and chronic inflammation of airways. Proinflammatory cytokines could contribute to this inflammatory process. This study was performed in order to analyze the genetic profile of proinflammatory cytokines in Iranian asthmatic patients. Patients and Methods  The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers. Results  The most frequent genotypes in our patients were TNF-α GA at position −308 (P = 0.001), TNF-α AA at position −238 (P = 0.01), IL-1α TC at position −889 (P = 0.0001), IL-1β TC at position −511 (P = 0.0001), and IL-1RA TC at position Mspa-I 11100 (P = 0.001). In contrast, the frequencies of the genotypes TNF-α GG at position −308 (P = 0.001), IL-1α CC at position −889 (P = 0.005), IL-1β CC at position −511 (P = 0.0001), and IL-1RA TT at position Mspa-I 11100 (P = 0.0001) in the patient group were significantly lower than controls. The most frequent haplotypes for TNF-α (positions 308, −238) was A/A in the patient group in comparison with controls (P = 0.0001). Conclusion  While environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Considering the high frequency of presence of TNF-α AG genotype (−308), it seems that the production of TNF-α in the asthmatic patients could be higher than normal subjects.     

T-Helper 1, T-Helper 2, and T-Regulatory Cytokines Gene Polymorphisms in Irritable Bowel Syndrome

Inflammation and mucosal immune system activation have an important role in irritable bowel syndrome (IBS), whereas genetic factors can control some immunological mediators. In this study, a number of polymorphic genes coding for T-helper 1, T-helper 2, and T-regulatory cytokines were genotyped in 71 patients with IBS, and the results were compared with controls. IL-4 CC genotype at position −590, IL-4 TT genotype at position −33, and IL-10 GA genotype at position −1082 were significantly overrepresented in the patients with IBS in comparison with controls (P < 0.001). The frequencies of the following haplotypes in the patient group were significantly higher than in the control group: IL-2 (−330, +160) GT haplotype (P = 0.002), IL-4 (−1098, −590, −33) TCC haplotype (P < 0.001), and TCT haplotype (P < 0.001). While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.     

Influence of sympatho-vagal balance on airway responsiveness in athletes

The increased prevalence of airway hyper-responsiveness (AHR) observed among athletes suggests that high-level training may contribute to the development of AHR. We investigated the possible influence of the sympatho-vagal balance on this phenomenon in 40 athletes and 10 sedentary controls. Each subject filled out a respiratory questionnaire, had a methacholine challenge, and measurements were made of their baseline plasma catecholamines [epinephrine (E), norepinephrine (NE) and dopamine (DA)] as a reflection of sympathetic tone, and their heart rate variability (SDNN: standard deviation of all normal-to-normal intervals) as an indicator of parasympathetic tone. The athletes had a 45% prevalence of AHR (defined as PC₂₀ < 16 mg/ml, where PC₂₀ is the concentration of methacholine inducing a 20% fall in the forced expiratory volume in 1 s, FEV₁) with a mean PC₂₀ of 21.2 mg/ml compared with 10% prevalence (mean PC₂₀: 74.4 mg/ml) in sedentary subjects (P < 0.01). Plasma catecholamine values were not significantly different between the two groups (all P > 0.05), but the estimated parasympathetic tone was higher in athletes (P=0.01). When data from all subjects were analyzed together, plasma E and NE correlated with PC₂₀ (r=0.39, P=0.005 and r=0.29, P < 0.005) but DA and SDNN did not (both P > 0.05). However, the ratios E/SDNN, NE/SDNN and DA/SDNN showed significant correlations with PC₂₀ (r=0.42, P < 0.01; r=0.33, P < 0.005 and r=0.31, P < 0.05, respectively). This study suggests that the sympatho-vagal balance may contribute to the increased AHR in the population studied but this influence alone cannot explain the higher prevalence of AHR in athletes. Accepted: 26 July 2000     

Expression of Raf-1 kinase inhibitory protein in carcinoma of the ampulla of Vater

Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human malignancies. We have recently demonstrated that reduced expression of RKIP is significantly associated with invasion and metastasis in periampullary carcinomas, including pancreatic carcinoma, gallbladder carcinoma, and extrahepatic bile duct carcinoma. In this study, we evaluated RKIP expression in ampulla of Vater (AoV) carcinoma and investigated its prognostic significance. Immunostaining for RKIP was performed for 80 and 21 cases with primary and nodal metastatic AoV carcinoma, respectively. RKIP expression was reduced in 32.5% (26/80) and 66.7% (14/21) of primary and nodal metastatic AoV carcinoma cases, respectively. This distribution of RKIP expression was statistically significant (P < 0.001). The reduction in RKIP expression was significantly associated with the presence of nodal (P = 0.008) and distant (P = 0.002) metastases, a higher TNM stage group (P = 0.010), lymphatic invasion (P < 0.001), vascular invasion (P < 0.001), and a shorter disease-free survival (DFS; P = 0.028) and distant metastasis-free survival (DMFS; P = 0.005). In addition, reduced RKIP expression was an independent prognostic predictor for worse DFS and DMFS (P = 0.032 and P = 0.036, respectively). Our data suggest that a reduction in RKIP expression contributes to invasion and metastasis in AoV carcinoma and is a significant prognostic marker in patients with AoV carcinoma.     

Lipid and lipoprotein profiles, cardiovascular fitness, body composition, and diet during and after resistance, aerobic and combination training in young women

The purpose of this study was to evaluate the effects of various modes of training on the time-course of changes in lipoprotein-lipid profiles in the blood, cardiovascular fitness, and body composition after 16 weeks of training and 6 weeks of detraining in young women. A group of 48 sedentary but healthy women [mean age 20.4 (SD 1) years] were matched and randomly placed into a control group (CG, n=12), an aerobic training group (ATG, n=12), a resistance training group (RTG, n=12), or a cross-training group that combined both aerobic and resistance training (XTG, n=12). The ATG, RTG and XTG trained for 16 weeks and were monitored for changes in blood concentrations of lipoprotein-lipids, cardiovascular fitness, body composition, and dietary composition throughout a 16 week period of training and 6 weeks of detraining. The ATG significantly reduced blood concentrations of triglycerides (TRI) (P < 0.05) and significantly increased blood concentrations of high-density lipoprotein-cholesterol (HDL-C) after 16 weeks of training. The correlation between percentage fat and HDL-C was 0.63 (P < 0.05), which explained 40% of the variation in HDL-C, while the correlation between maximal oxygen uptake (V˙O_2max) and HDL-C was 0.48 (P < 0.05), which explained 23% of the variation in HDL-C. The ATG increased V˙O_2max by 25% (P < 0.001) and decreased percentage body fat by 13% (P < 0.05) after 16 weeks. Each of the alterations in the ATG had disappeared after the 6 week detraining period. The concentration of total cholesterol (TC), TRI, HDL-C and low density lipoprotein-cholesterol in the blood did not change during the study in RTG, XTG and CG. The RTG increased upper and lower body strength by 29% (P < 0.001) and 38%, respectively. The 6 week detraining strength values obtained in RTG were significantly greater than those obtained at baseline. The XTG increased upper and lower body strength by 19% (P < 0.01) and 25% (P < 0.001), respectively. The 6 week detraining strength values obtained in XTG were significantly greater than those obtained at baseline. The RTG, XTG and CG did not demonstrate any significant changes in either V˙O_2max, or body composition during the training and detraining periods. The results of this study suggest that aerobic-type exercise improves lipoprotein-lipid profiles, cardiorespiratory fitness and body composition in healthy, young women, while resistance training significantly improved upper and lower body strength only. Accepted: 9 April 2000     

Classical and Follicular Variant Papillary Thyroid Carcinoma: Comparison of Clinical,Ultrasonographical, Cytological,and Histopathological Features in 444 Patients

Follicular variant papillary thyroid carcinoma (FVPTC) is the most common variant of papillary thyroid carcinoma (PTC) after classical PTC (CPTC). In this study, we aimed to compare functional status, ultrasonographical features, cytological results, and histopathological characteristics of patients with CPTC and FVPTC. Preoperative thyroid functions, thyroid autoantibodies, ultrasonographical features, cytology, and histopathology results of 354 (79.9%) CPTC and 90 (20.3%) FVPTC patients were reviewed retrospectively. Sex distribution, mean age, thyroid autoantibody positivity, and thyroid dysfunctions were similar in two groups. Among 320 patients with preoperative ultrasonography (US) findings, a hypoechoic halo was observed more frequently (p = 0.003), and marginal irregularity was observed less commonly (p = 0.024) in FVPTC lesions. In CPTC, rate of malignant cytology (p = 0.001), and in FVPTC, rate of suspicious cytology (p < 0.001) were significantly higher. Histopathologically, mean tumor diameter was markedly higher in FVPTC compared to CPTC (16.89 ± 13.86 vs 10.64 ± 9.70 mm, p < 0.001), while capsular invasion and extrathyroidal spread were significantly lower in patients with FVPTC (p = 0.018 and p = 0.039, respectively). FVPTC tend to have more benign features in US and less malignant results in cytology. Higher tumor size in FVPTC might be explained by the recognition of clinical importance of these lesions after reaching particular sizes due to benign US features.     

Haplotype analysis of XRCC1 (at codons 194 and 399) and breast cancer risk, a case–control study

DNA in most cells is regularly damaged by endogenous and exogenous mutagens. Among DNA repair systems, the base excision repair pathway is responsible for the repair of oxidative DNA damage and single-strand breaks. The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. Several polymorphisms in the XRCC1 gene have been described, including Arg194Trp (db SNP rs. 1799782). Since it has been suggested that the XRCC1 codon 194 polymorphism might be associated with significant alterations in the DNA repair capacity, the present study was undertaken. Blood samples from 186 females with breast cancer and 187 age- and sex-matched healthy individuals were collected. The genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism method. Allele frequency of 194Trp was low in both cancer patients and controls (0.0968 and 0.0802, respectively) and exhibited a similar distribution within both groups (odd ratio = 1.22, 95% confidence interval: 0.74–2.04, P = 0.426). The association between Arg194Trp polymorphism and breast cancer risk was not significant neither in Trp/Trp (P = 1.0) nor Arg/Trp (P = 0.273) genotypes compared with the Arg/Arg genotype. The close physical proximity of the polymorphisms at codons 194 and 399 of XRCC1 place them in linkage disequilibrium (patients: D′ = 0.8386, P < 0.001; controls: D′ = 1.0, P < 0.001). However, no significant difference between frequencies of the four types of haplotypes among cases and controls (P > 0.05) was noted.     

Thyroid hormones and their correlations with serum glucose, beta hydroxybutyrate, nonesterified fatty acids, cholesterol, and lipoproteins of high-yielding dairy cows at different stages of lactation cycle

The relationships between circulating thyroid hormones and serum glucose, beta hydroxybutyrate (BHB), nonesterified fatty acid (NEFA), cholesterol and lipoproteins of high-yielding dairy cows were studied in 125 adult Holsteins at various stages of lactation cycle: early (far-off) dry period (n = 24), late (close-up) dry period (n = 10), fresh cows (n = 22), early lactation (n = 13), mid-lactation (n = 27) and late lactation (n = 29). Decreased levels of thyroxin (T₄) and triiodothyronine (T₃) were noted in peripartum cows which were extended to mid- and late-lactation cows, respectively. In fresh cows, glucose showed correlations with T₄ (r = 0.619, P < 0.01) and T₃ (r = 0.627, P < 0.01). In the same cows there were correlations between T₄ and BHB (r = 0.590, P < 0.01) and NEFA (r = 0.470, P < 0.01). In late dry cows, free thyroxin (fT₄) showed correlations with triglyceride (TG) and very-low-density lipoprotein (VLDL; r = −0.638, P < 0.05). Pooled data of the various stages of lactation cycle revealed correlations between glucose and T₄ (r = 0.20, P < 0.05), glucose and T₃ (r = 0.395, P < 0.01), cholesterol and T₃ (r = −0.201, P < 0.05), and free triiodothyronine (fT₃) and high-density lipoprotein (HDL; r = 0.178, P < 0.05). It appears that the time and the pattern of changes and/or correlations of serum thyroid hormones and lipid fractions may vary among dairy cows and other animals.     

Relationship Between Eosinophilia and Levels of Chemokines (CCL5 and CCL11) and IL-5 in Bronchoalveolar Lavage Fluid of Patients With Mustard Gas-Induced Pulmonary Fibrosis

Objective Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of IL-5, RANTES (CCL5) and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF). Patients Fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group. Intervention Pulmonary function tests, tests for D_LCO, computed tomography scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases. Results Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03; r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too. Conclusion A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis due to SM gas inhalation has been demonstrated, suggesting that these C–C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.     

Effect of different levels of cigarette smoking on lipid peroxidation, glutathione enzymes and paraoxonase 1 activity in healthy people

Abstract The purpose of this study was to examine the effect of different levels of cigarette smoking on lipid peroxidation, glutathione enzymes and paraoxonase 1 (PON1) activity in a healthy population. The study included 130 subjects who were classified as mild (≤10 cigarettes daily, Group I, n=30), moderate (11–20 cigarettes daily, Group II, n=35), heavy (>20 cigarettes daily, Group III, n=33) and never smokers (controls, Group IV, n=32). Malondialdehyde (MDA) levels, PON1 and erythrocyte glutathione enzyme activities were measured. MDA levels were significantly higher in smokers than never smokers (P<0.05 for Group I, P<0.001 for Group II and III). PON1 activity was significantly lower in heavy smokers (P<0.001). Glutathione peroxidase (GSH-Px) activity was significantly lower in the smokers (P<0.0001). Glutathione reductase (GR) activity was significantly higher in smokers (P<0.0001). MDA levels negatively correlated with PON1 and GSH-PX activities (P<0.01), whereas they positively correlated with GR activities (P<0.001). At every level, cigarette smoking is associated with increased lipid peroxidation and causes an impairment in antioxidant systems.     

Dose dependency of prednisolone tertiary-butylacetate (PTBA) treatment on the establishment and site predilection of Echinococcus multilocularis in an alternative definitive host model using Mongolian gerbil (Meriones unguiculatus)

Mongolian gerbils (Meriones unguiculatus) were orally inoculated with 10,000 protoscoleces of Echinococcus multilocularis per head after being divided into five groups (A–E). Each group was dosed with prednisolone tertiary-butylacetate (PTBA) as follows: A, 0 mg; B, 0.5 mg; C, 2 mg; D, 5 mg; and E, 10 mg/head. All animals were injected subcutaneously with control solvent or PTBA every other day from 6 days pre- to 6 days post-infection. Autopsy was performed at 7 days post-infection. Doses of PTBA and the number of worms recovered showed a positive correlation (r=0.929, P < 0.0001). In groups A, B and C, the predilection site of the worms in the small intestine could not be determined, while in group D the worms were found more in the anterior part. In group E, the predilection site was the anterior part, followed by the middle and the posterior parts of the small intestine (Fisher's test: P < 0.01). The number of worms recovered from the anterior and the middle part of the small intestine also correlated positively with PTBA dose (anterior part: r=0.930, P < 0.0001, middle part: r=0.917, P < 0.0001). All groups of the PTBA-treated animals showed significant loss of weight compared to the non-treated animals (P < 0.01). Received: 26 September 1999 / Accepted: 24 November 1999     

Characterization of the best anatomical sites in screening for methicillin-resistant Staphylococcus aureus colonization

The purpose of this study was to identify differences in the sensitivity of anatomical sites sampling for methicillin-resistant Staphylococcus aureus (MRSA) colonization related to age, gender, clinical situation, and acquisition source as a base for screening protocols. We used a database that included all MRSA-positive cultures (Carmel Medical Center, 2003–2006) taken from nares, throat, perineum, and infection sites. The study population of 597 patients was divided into: “screening sample” (SS), which were cases of routine screening, and “clinical diagnostic sample” (CDS), which were patients with concurrent MRSA infection. MRSA acquisition sources were classified as internal medicine, surgical, referral patients, or intensive care unit (ICU). CDS patients were older than SS patients (median age 78 vs. 74 years, p = 0.0002), more commonly throat colonized (47.5% vs. 31.8%, p = 0.0001), and colonized in more multiple sites (65.7% vs. 43.3% were colonized in three sites in the CDS and SS groups, respectively, p < 0.001) than SS patients. In the SS, group throat colonization was higher in internal medicine wards than in the ICU (odds ratio [OR] = 3.98, p < 0.0001). In the CDS group, perineal colonization was more common in referral patients than in the ICU (OR = 4.52, p < 0.05). Patient age was the most influential factor on nares and multiple sites colonization in the SS and CDS groups, respectively. Our data support multiple sites sampling. Throat cultures are crucial in MRSA-infected patients and internal medicine ward patients. Multiple body sites colonization is more likely in older or MRSA-infected patients, affecting decisions regarding eradication using topical antibiotics.     

DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema

The purpose of this investigation was to evaluate a rapid quantitative real-time polymerase chain reaction (PCR) for the direct detection and quantification of pneumococcal DNA bacterial load (DBL) in patients with pneumonia and empyema. DBL and molecular serotype detection was determined by DNA quantification of the pneumolysin (ply) gene and an additional capsular gene by real-time PCR. Plasma or pleural fluid samples from children and adolescents with confirmed pneumococcal pneumonia were analyzed. DBL was correlated with clinical parameters and outcomes. One hundred and sixty-nine patients with pneumococcal pneumonia (145 empyema) had bacterial cultures and real-time PCR assays performed. Among them, 41 (24.3%) had positive results for both, 4 (2.4%) had positive culture alone, and 124 (73.3%) had positive real-time PCR alone. The pleural fluid DBL was lower in patients with prior antibiotics (p = 0.01) and higher in patients with positive culture (p < 0.001). The pleural fluid DBL was positively correlated with serum C-reactive protein (p = 0.009), pleural fluid neutrophils (p < 0.001), and pleural fluid glucose (p < 0.001). The plasma and pleural fluid DBL were higher in patients with ≥8 days of hospital stay (p = 0.002), and the pleural fluid DBL was positively correlated with the number of hours of pleural drainage (p < 0.001). Quantification of pneumococcal DBL by real-time PCR may be helpful for the diagnosis and clinical management of pediatric patients with pneumonia and empyema     

Higher Doses of Subcutaneous IgG Reduce Resource Utilization in Patients with Primary Immunodeficiency

The recommended dose of IgG in primary immunodeficiency (PID) has been increasing since its first use. This study aimed to determine if higher subcutaneous IgG doses resulted in improved patient outcomes by comparing results from two parallel clinical studies with similar design. One patient cohort received subcutaneous IgG doses that were 1.5 times higher than their previous intravenous doses (mean 213 mg/kg/week), whereas the other cohort received doses identical to previous subcutaneous or intravenous doses (mean 120 mg/kg/week). While neither cohort had any serious infections, the cohort maintained on higher mean IgG dose had significantly lower rates of non-serious infections (2.76 vs. 5.18 episodes/year, P < 0.0001), hospitalization (0.20 vs. 3.48 days/year, P < 0.0001), antibiotic use (48.50 vs. 72.75 days/year, P < 0.001), and missed work/school activity (2.10 vs. 8.00 days/year, P < 0.001). The higher-dose cohort had lower health care utilization and improved indices of well being compared to the cohort treated with traditional IgG doses.     

Effects on spectrum and susceptibility patterns of isolates causing bloodstream infection by restriction of fluoroquinolone prophylaxis in a hematology–oncology unit

The emergence of fluoroquinolone-resistant gram-negative organisms has been demonstrated in patients given fluoroquinolone prophylaxis. To prevent increases in resistant bacteria, we restricted prophylactic use of fluoroquinolones. The spectrum and susceptibility patterns of isolates causing bloodstream infection (BSI) were assessed in patients receiving chemotherapy during periods of routine prophylaxis (period A: October 2001 to May 2003) and restricted prophylaxis (period B: June 2003 to January 2005). The total number of patients receiving chemotherapy was 442 during period A and 365 during period B. No significant differences were seen between periods with respect to patient characteristics. BSI was identified in 42 patients (44 episodes) during period A and 69 patients (74 episodes) during period B. Incidence of BSI increased significantly from 10.0% (44/442) during period A to 20.3% (74/365) during period B (P < 0.0001). Rate of Enterobacteriaceae BSI increased significantly, from 2.0% (9/442) during period A to 8.2% (30/365) during period B (P < 0.0001). For all BSI episodes, the proportion of BSI with gram-positive cocci decreased from 63.6% (28/44) during period A to 44.6% (33/74) during period B (P = 0.045), while the proportion of BSI with Enterobacteriaceae increased from 20.5% (9/44) to 40.5% (30/74) (P < 0.0001). The proportion of fluoroquinolone-resistant Enterobacteriaceae BSI for all Enterobacteriaceae BSI decreased from 75% (9/12) during period A to 17% (5/30) during period B (P = 0.0078). Restriction of fluoroquinolone prophylaxis affects the etiology of BSI and reduces the proportion of drug-resistant organisms.     

Clinical features and treatment outcomes of vancomycin-intermediate <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> (VISA) and heteroresistant vancomycin-intermediate <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> (hVISA) in a tertiary care institution in Singapore

This retrospective case–control study was undertaken to review the clinical features associated with heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections and the local impact they have on clinical outcome. Compared with vancomycin-susceptible S. aureus (n = 30), hVISA and VISA infections (n = 10) are found to be associated with a longer period of prior glycopeptide use (P = 0.01), bone/joint (P < 0.01) and prosthetic infections (P = 0.04), as well as treatment failure, as evidenced by longer bacteremic (P < 0.01) and culture positivity (P < 0.01) periods. This was observed to have resulted in longer hospital length of stay (P < 0.01) and total antibiotic therapy duration (P = 0.01). There was, however, no significant difference in the overall patient mortality or the hospitalization cost (P = 0.12) in both groups. Clinicians should be cognizant of the association between hVISA/VISA with high bacterial load deep-seated infections. We recommend targeted and even universal screening for hVISA/VISA in methicillin-resistant S. aureus (MRSA) infections.     

Expression of Krűppel-like factor 5 in gastric cancer and its clinical correlation in Taiwan

Krűppel-like factors (KLFs), highly conserved zinc-finger proteins, play either anti- or pro-proliferation roles in different human cancers through regulating a wide range of genes’ expression. Here, we investigated the expression of KLF5 in gastric cancers and its correlation with clinicopathological parameters and overall survival rates. In this study, KLF5 expression was measured by an immunohistochemical microarray assay of tissue taken from 76 surgical specimens. Higher KLF5 expression was significantly associated with lower tumor grade (P < 0.001). Nuclear staining of the KLF5 expression was significantly associated with a higher tumor grade (P = 0.000), higher clinical stage (P = 0.019), lymph node status (P = 0.016), and 2-year survival (P = 0.017). Patients with nuclear staining of KLF5 had a significantly lower disease-free survival rate compared to patients with negative nuclear staining, as defined by a log-rank test (P = 0.041). Our results revealed that KLF5 may play an oncogenetic role in gastric carcinogenesis.     

CD24 expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression

Expression of the mucin-like adhesion molecule CD24 has been implicated in the progression of several types of cancer and has been identified as new prognostic factor. We evaluated CD24 expression in 268 consecutive cases of upper urinary tract urothelial carcinoma with respect to associations with tumour stage, grade, angioinvasion and infiltrative growth pattern using a tissue microarray technique and correlated data with patient outcome. CD24 expression was demonstrated in 161/259 (62%) evaluable tumours and was associated with high tumour stage [77/139 (55%) pTa/pT1 vs 84/120 (70%) pT2–pT4; P = 0.02] and high tumour grade [68/139 (49%) low vs 93/120 (78%) high grade; P < 0.001] as well as presence of angioinvasion (P = 0.002) and infiltrative pattern of invasion (P = 0.007). Patients with CD24-positive tumours tended to have a higher risk of disease progression (P = 0.065). Multivariate analysis, however, proved pT stage >1 [P < 0.001, risk ratio (RR) = 5.87, 95% confidence interval (CI) = 2.88–11.95] and high tumour grade (P < 0.001, RR = 3.30, 95% CI 1.75–6.22) as only independent predictors of metastatic disease. In conclusion, CD24 expression in upper urinary tract urothelial cancer is associated with advanced tumour stage and high tumour grade as well as histopathological features indicative of aggressive tumour behaviour, but it lacks independent impact on patient outcome.