Pharmacokinetic modelling and validation of the half-life extension needed to reduce the burden of infusions compared with standard factor VIII.

INTRODUCTION: Currently, no universally accepted definition of extended half-life (EHL) recombinant FVIII (rFVIII) exists. Identifying the minimum half-life extension ratio required for a reduction in dosing frequency compared with standard rFVIII could enable a more practical approach to decisions around prophylaxis with EHL rFVIII. AIM: To identify the half-life extension ratio required to decrease rFVIII dosing frequency by at least 1 day while maintaining the proportion of patients with plasma rFVIII levels above 1 IU/dL and without increasing the total weekly dose. METHODS: A previously published population pharmacokinetic model for standard rFVIII was used to estimate the percentage of patients with factor VIII (FVIII) levels always >1 IU/dL using various benchmark regimens. Using modelling, dosing frequency was reduced while rFVIII half-life was extended until the percentage of patients with FVIII >1 IU/dL equalled that of the benchmark regimen. RESULTS: Benchmark 3×/wk dosing totalling 100 IU/kg/wk of rFVIII resulted in 56.6% of patients with FVIII levels always >1 IU/dL. With 2×/wk dosing, totalling 80 or 90 IU/kg/wk, half-life extensions required to maintain 56.6% of patients at FVIII levels >1 IU/dL were 1.30 and 1.26, respectively. A half-life extension ratio of 1.33 was required to change dosing from every 48 hours to every 72 hours (both at 105 IU/kg/wk) while maintaining 92.8% of patients with FVIII >1 IU/dL. CONCLUSION: Based on this investigation, EHL rFVIII products should have a minimum half-life extension ratio of 1.3 to provide a reduction in dosing frequency from 3× to 2×/wk compared with standard rFVIII products while maintaining the same minimum FVIII trough level.

Effect of endoscopy screening on stage at gastric cancer diagnosis: results of the National Cancer Screening Programme in Korea.

BACKGROUND: Although gastric cancer screening is common among countries with a high prevalence of gastric cancer, there is little data to support the effectiveness of this screening. This study was designed to determine the differences in stage at diagnosis of gastric cancer according to the screening history and screening method (upper gastrointestinal series (UGIS) vs endoscopy). METHODS: The study population was derived from the National Cancer Screening Programme (NCSP), a nationwide organised screening programme in Korea. The study cohort consisted of 19 168 gastric cancer patients who had been diagnosed in 2007 and who were invited to undergo gastric cancer screening via the NCSP between 2002 and 2007. RESULTS: Compared with never-screened patients, the odds ratios for being diagnosed with localised gastric cancer in endoscopy-screened patients and UGIS-screened patients were 2.10 (95% CI=1.90-2.33) and 1.24 (95% CI=1.13-1.36), respectively. CONCLUSIONS: Screening by endoscopy was more strongly associated with a diagnosis of localised stage gastric cancer compared with screening by UGIS.

Do newly built homes affect rhinitis in children? The ISAAC phase III study in Korea.

BACKGROUND: As Korea has experienced rapid economic development, the lifestyles of Koreans have become more Westernized, in terms of urbanization and dietary habits. Also, the prevalences of allergic diseases, such as rhinitis, asthma, and dermatitis, have increased rapidly. This study aimed to identify the factors influencing the symptoms of rhinitis conditions, including rhinitis, allergic rhinitis, overlapped rhinitis, and overlapped allergic rhinitis, among Korean children aged 6-7 years. METHODS: The study subjects were drawn from participants in the International Study of Asthma and Allergies in Childhood (ISAAC) study in 2010 and were aged 6-7 years. We analysed data for a total of 3804 children. RESULTS: The prevalences of symptoms suggestive of rhinitis and allergic rhinitis in the previous 12 months were 43.4% and 22.1%, respectively. For overlapped rhinitis and overlapped allergic rhinitis, only 2.5% and 1.9% of the children had overlapping symptoms, having rhinitis with asthma and eczema simultaneously. Gender, a parental history of allergic disease, mould or dampness at home, and the risk factors for 'sick building syndrome' (SBS) were risk factors influencing rhinitis diseases. In particular, a history of moving to a newly built home in the child's infancy was strongly associated with symptoms of all the rhinitis diseases examined. CONCLUSIONS: This study identified patterns of the prevalence of rhinitis conditions among Korean children that were similar to those reported in Western countries. We confirmed that a history of moving to a newly built home during infancy was associated with a considerable risk of rhinitis conditions.

Giardia lamblia binding immunoglobulin protein triggers maturation of dendritic cells via activation of TLR4-MyD88-p38 and ERK1/2 MAPKs.

Much remains unknown about the mammalian immune response to Giardia lamblia, a protozoan pathogen that causes diarrhoeal outbreaks. We fractionated protein extracts of G. lamblia trophozoites by Viva-spin centrifugation, DEAE ion exchange and gel filtration chromatography. Resultant fractions were screened for antigenic molecules by western blots analysis using anti-G. lamblia antibodies (Abs), resulting in identification of G. lamblia binding immunoglobulin protein (GlBiP). Maturation of mouse dendritic cells (DCs) in response to recombinant GlBiP (rGlBiP) was detected by increased expression of surface molecules such as CD80, CD86 and MHC class II; these mature DCs, produced pro-inflammatory cytokines (TNF-α, IL-12 and IL-6). Especially, the truncated rGlBiP containing the heat-shock protein 70 domain-induced cytokine production from mouse DCs. rGlBiP-induced DC activation was initiated by TLR4 in a MyD88-dependent way and occurred through activation of p38 and ERK1/2 MAPKs as well as increased activity of NF-κB and AP-1. Moreover, CD4(+) T cells stimulated with rGlBiP-treated DCs produced high levels of IL-2 and IFN-γ. Together, our results suggest that GlBiP contributes to maturation of DCs via activation of TLR4-MyD88-p38, ERK1/2 MAPK, NF-κB and AP-1.

Clinical outcomes of bacteraemia in cellulitis of the leg.

BACKGROUND: Infections of the blood are associated with high mortality and morbidity. In cellulitis, the utility of blood cultures remains controversial because of their relatively low bacterial yield. However, some important but less well studied aspects include risk factors for bacteraemia, the effects of bacteraemia on the length of hospitalization and on morbidity and mortality rates. AIM: To determine the incidence of bacteraemia in cellulitis in an inpatient cohort; to identify risk factors for bacteraemia in cellulitis; and to assess length of hospitalization stay, rate of recurrence of cellulitis, and mortality in patients with cellulitis and bacteraemia. METHODS: Records of 214 patients diagnosed with cellulitis were reviewed. Blood cultures, length of hospitalization stay, rate of recurrence of cellulitis, mortality, coexistent dermatoses and local factors predisposing to cellulitis and comorbidities were analyzed. RESULTS: The incidence of bacteraemia was 10.8%. Mean duration of hospitalization was longer (P < 0.01) and recurrence (P < 0.01) was higher in patients with bacteraemia. There was no difference in mortality between patients with and patients without bacteraemia (P = 0.47). Risk factors for bacteraemia included lymphoedema (P < 0.01), presence of an ipsilateral orthopaedic implant (P < 0.01), total white blood cell (WBC) count > 13.5 × 10(6) µL (P < 0.01, liver cirrhosis (P = 0.02) and chronic kidney disease (P = 0.04). CONCLUSIONS: Blood cultures should be performed for patients with cellulitis who have factors increasing the risk of bacteraemia, such as presence of lymphoedema, ipsilateral orthopaedic device implantation, leucocytosis of > 13.5 × 10(6) µL, liver cirrhosis or chronic kidney disease, and other forms of immunosuppression. Bacteraemia in cases of cellulitis of the leg is a prognostic factor for increased length of hospitalization stay and recurrence of cellulitis.

Association study of polymorphisms between the Radixin gene and rheumatoid arthritis in a Korean population.

Radixin (RDX) is part of the ezrin-radixin-moesin (ERM) protein family. It functions as a membrane-cytoskeletal linker in actin-rich cell surface structures and is thought to be essential for cortical cytoskeleton organization, cell motility, adhesion, and proliferation. An increase in phosphorylated ERM in fibroblast-like synoviocytes contributes to rheumatoid arthritis (RA) synovial hyperplasia. We examined the genetic association between the RDX gene and RA in a Korean population. To identify the relationship between RDX gene polymorphisms and RA, we genotyped 2 single nucleotide polymorphisms (SNPs; rs11213326 and rs12575162) of RDX using a direct sequencing method in 296 RA patients and 493 control subjects. In this study, the 2 SNPs showed no association with RA disease susceptibility. However, further analysis based on clinical information of the RA patient group showed that the SNPs were associated with the erythrocyte sedimentation rate (ESR) in RA patients. These data suggest an association between RDX polymorphisms and the clinical features of RA patients, particularly the ESR.

Gallium oxide (Ga2O3) energy dependent scintillation response to fast neutrons and flash gamma-rays.

Gallium oxide is a newly emerged ultrawide bandgap (4.9 eV) semiconductor that is suitable as a combined electronics and radiation detection platform. We have experimentally demonstrated fast neutron and gamma-ray scintillation from Czochralski-grown ß-Ga2O3 in a recent series (October 2023) of experiments at the unmoderated pulsed neutron spallation source located at the Los Alamos Neutron Science Center. Using the neutron time-of-flight (TOF) technique and a fast-gated intensified CCD camera, we observed energy-dependent neutron scintillation for neutron energies ranging from 1 to 400 MeV, including the 14.1 MeV neutron energy relevant to D-T fusion. Neutron flux is quantified and calibrated by cascading the scintillator after the fission chamber, enabling a detailed analysis of temporal and energy-dependent characteristics of the scintillation events. A pronounced scintillation signal from the spallation gamma flash with a temporal full width of half maximum of ∼4 ns is indicative of the material's rapid response. Neutron energy dependent scintillation is observed using the TOF method at a 22.6-m distance from the neutron source. These results highlight the possibility of developing a Ga2O3 based fusion neutron diagnostic platform integrated with both scintillation and electronics functions on the integrated chip scale.

LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients.

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

The impact of phosphorylated AMP-activated protein kinase expression on lung cancer survival.

BACKGROUND: The aim of this study is to investigate the prognostic role of phosphorylated AMP-activated protein kinase (pAMPK) in surgically resected non-small-cell lung cancer (NSCLC). METHODS: Immunohistochemical staining of pAMPK was carried out on tissue microarrays containing 463 samples obtained from patients with NSCLC and correlated with clinicopathological characteristics and survival. RESULTS: pAMPK expression levels were significantly higher in never smokers versus former smokers versus current smokers (P=0.045). A positive pAMPK expression was associated with increased overall survival (OS) and recurrence-free survival (RFS) (P=0.0009 and P=0.0007, respectively). OS and RFS were statistically superior in pAMPK-positive than in pAMPK-negative patients with adenocarcinoma (ADC; median OS: 5.6 and 4.2 years, respectively, P=0.0001; median RFS: 5.0 and 2.4 years, respectively, P=0.001), whereas they were similar in those patients with squamous cell carcinoma. Multivariate analysis confirmed that pAMPK positivity was associated with OS [hazard ratio (HR)=0.574, 95% confidence interval (CI) 0.418-0.789, P=0.0006) and RFS (HR=0.608, 95% CI 0.459-0.807, and P=0.0006), independent of clinical covariates. CONCLUSIONS: High pAMPK expression levels are associated with increased survival in patients with NSCLC, especially those with ADC. Our results support further evaluation of AMP-activated protein kinase as a potential prognostic and therapeutic target for lung cancer.

Excretory-secretory products of Giardia lamblia induce interleukin-8 production in human colonic cells via activation of p38, ERK1/2, NF-κB and AP-1.

Giardia lamblia, a pathogen causing diarrhoeal outbreaks, is interesting how it triggers immune response in the human epithelial cells. This study defined the crucial roles of signalling components involved in G. lamblia-induced cytokine production in human epithelial cells. Incubation of the gastrointestinal cell line HT-29 with G. lamblia GS trophozoites triggered production of interleukin (IL)-1ß, IL-8 and tumour necrosis factor (TNF)-α. IL-8 production was not significantly decreased by physically separating the HT-29 cells and G. lamblia GS trophozoites. Indeed, treatment of HT-29 with G. lamblia excretory-secretory products (ESP) induced IL-8 production. Electrophoretic mobility gel shift and transfection assays using mutagenized IL-8 promoter reporter plasmids indicated that IL-8 production by G. lamblia ESP occurs through activation of two transcriptional factors, nuclear factor kappaB (NF-κB) and activator protein 1 (AP-1) in HT-29 cells. In addition, activation of two mitogen-activated protein kinases (MAPKs), p38 and ERK1/2, was also detected in the HT-29 cells stimulated with G. lamblia ESP. Selective inhibition of these MAPKs resulted in decreased production of ESP-induced IL-8. These results indicate that activation of p38, ERK1/2 MAPK, NF-κB and AP-1 comprises the signalling pathway responsible for IL-8 production by G. lamblia ESP.

Clinical evaluation of the computerized chronic urticaria-specific quality of life questionnaire in Korean patients with chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is a common skin disorder that affects the well-being and quality of life (QOL) of patients. Recently, we developed and validated a questionnaire for measuring QOL in Korean patients with CU, called the Chronic Urticaria-Specific Quality of Life (CU-QOL) questionnaire. AIM: To evaluate the clinical significance of a computerized version of the CU-QOL, in adult patients with CU. METHODS: This was a cross-sectional observational study that enrolled 249 Korean patients with CU from five university hospitals and measured computerized CU-QOL scores and Urticaria Activity Score (UAS) simultaneously. The internal consistency of the computerized CU-QOL was analysed using Cronbach α. To identify clinical correlations between the CU-QOL and patient characteristics, the atopic status and serum autoantibodies, including antinuclear, antithyroglobulin and antimicrosome antibodies, were measured. Multiple linear regression models were used to identify CU-QOL predictors. RESULTS: Cronbach α was 0.94 for the overall computerized CU-QOL score. The CU-QOL scores correlated significantly with the UAS (r= -0.49, P<0.001). Of the factors aggravating CU, delayed pressure, sunlight exposure and emotional stress significantly influenced the overall CU-QOL scores in the univariate analysis. Multivariate regression models indicated that UAS and emotional stress were significant predictors of the four domains and of the total CU-QOL scores. CONCLUSIONS: The computerized CU-QOL is a convenient and valid tool for measuring QOL in patients with CU. This study suggests that UAS, dermatographism and emotional stress are strong CU-QOL predictors in Korean patients with CU.

Effects of zoledronic acid on bone mineral density during aromatase inhibitor treatment of Korean postmenopausal breast cancer patients.

The age distribution of breast cancer patients in Korea, where most are less than 60 years of age and have recently entered menopause, differs from that in the West. The aim of this study was to evaluate bone mineral density (BMD) changes in Korean breast cancer patients treated with an aromatase inhibitor (AI) either alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar spine and hip were evaluated in 107 patients receiving AI treatment, of which 59 were treated in combination with ZA. The mean age of the patients was 54.9 years, and the median follow-up period was 38.2 months. With AI treatment alone, BMD loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18 and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and 6.82%) after treatment. In contrast, the combination treatment resulted in increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%, respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after treatment. BMD loss in the lumbar spine was significantly greater in AI alone-treated women who had entered menopause within the past year compared with those who had entered menopause more than 1 year ago, when measured 12 and 24 months after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively inhibited AI-associated bone loss, independent of the postmenopausal interval. Because the proportion of patients in this study who had recently entered menopause was high, bone loss in Korean breast cancer patients treated with AI alone was higher than data reported from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective in preventing AI-induced bone loss in Korean postmenopausal breast cancer patients.

Association of thromboxane A2 receptor (TBXA2R) gene polymorphism in patients with aspirin-intolerant acute urticaria.

BACKGROUND: The thromboxane A2 receptor (TBXA2R) is a potent broncho- and vaso-constrictor and is associated with leukotriene synthesis. Polymorphisms in the TBXA2R gene have been linked to atopy, asthma, and atopic dermatitis. This study evaluated the association between genetic TBXA2R variants and the development of acetyl salicylic acid (ASA)-intolerant acute urticaria (AIAU). METHODS: AIAU patients (n=167), ASA-intolerant chronic urticaria (AICU) patients (n=149), and healthy controls (NC) (n=265) were included. All patients were enrolled at Ajou University Hospital in Suwon, Korea. Two TBXA2R polymorphisms (-4684T>C and 795T>C) were genotyped by primer extension using a SNAPshot ddNTP primer extension kit. Luciferase activity was measured using a dual-luciferase reporter assay kit. An electrophoretic mobility shift assay (EMSA) was performed using a nuclear extract from a human mast cell line (HMC-1). RESULTS: Genetic association data demonstrated that compared with NC subjects, AIAU patients had a significantly higher frequency of the homozygous TT genotype of TBXA2R-4684T>C (P=0.005, P(corr) =0.03). No differences were identified between the AICU and the NC groups. Luciferase activity, reflecting promoter activity, was significantly lower with the TBXA2R-4684T-containing construct than with the -4684C-containing construct (P<0.001); the activity decreased further upon co-transfection with ETS-like gene transcription factor-1 (ELK-1) (P=0.012). EMSA revealed that the -4684T allele produced a specific shifted band, with a greater affinity than that produced by the -4684C allele. CONCLUSION AND CLINICAL RELEVANCE: These results suggest that the TBXA2R-4684T allele may be associated with lower TBXA2R expression, which may contribute to the development of the AIAU phenotype.

A comparison of mortality and cardiac biomarker response between three outbred stocks of Sprague Dawley rats treated with isoproterenol.

The authors compared the mortality and cardiac biomarker responses in three outbred stocks of Sprague Dawley rats (CD/IGS, Sasco, Harlan) treated with isoproterenol hydrochloride. Cardiac injury was confirmed by histologic evaluation, and increases in cardiac troponin I concentration in serum were measured by two methods. CD/IGS rats had a higher incidence and earlier mortality compared with Sasco or Harlan rats. Harlan rats had lower severity scores for cardiomyocyte degeneration/necrosis compared with the other stocks. Post-isoproterenol treatment cardiac troponin I concentrations were greater in CD/IGS and Sasco rats compared with Harlan rats. Concentrations of cardiac troponin T followed a similar pattern to that of cardiac troponin I in rats treated with isoproterenol. Myosin, light chain 3 concentrations increased in all rats treated with isoproterenol, but there was no difference between the three stocks in the magnitude or pattern of the dose response. Increases in fatty acid binding protein 3 concentrations were detected in only the highest dose group at the earliest timepoint postdose for all three stocks of rats. Results of these studies illustrate the need for investigators to recognize the potential differences in response between stocks of Sprague Dawley rats treated with cardiotoxicants or novel chemical entities.

Factors associated with the intention to have colorectal cancer screening in Korean adults.

The purpose of this study was to investigate the factors related to screening intention in a population-based screening programme for colorectal cancer. The data were taken from the 2008 Korean National Cancer Screening Survey. We conducted a nationwide survey with trained interviewers using a questionnaire. A total of 2038 participants agreed to answer the survey. There were 955 study subjects aged ≥ 50 years in the target age group for colorectal cancer screening. Colorectal cancer screening behaviour and demographic characteristics were collected to evaluate intention for colorectal cancer screening and related factors. Descriptive statistics and multiple logistic regression were used in the analysis. The lifetime screening rate was 50.4% (50.9% for men and 49.8% for women). The screening rate with recommendation was 39.7% (39.3% for men and 40.1% of women). The odds ratios of intention to be screened increased significantly in younger subjects and those screened with double-contrast barium enema or colonoscopy. 'Without any symptoms' was reported as the most frequent reason for non-attendance or no intention to be screened. Age and recent screening methods were important factors related to intention to be screened for colorectal cancer. Further research is needed to identify remaining barriers to screening.

Satisfaction with mammography in the National Cancer Screening Programme participants of age 40s in Korea.

The aim of this study was to evaluate satisfaction with the National Cancer Screening Programme of mammography in Korea and to examine the association between subscales of satisfaction and general satisfaction. We conducted a cross-sectional telephone survey for women who had obtained a National Cancer Screening Programme mammographic screening at general hospitals between May and October 2008. The present study included 2005 women in their forties. We performed multivariate linear regression using dependent variable as general satisfaction and independent variables as subscales of satisfaction, such as pre-screening information transfer, staff interpersonal skills, physical surroundings and results reporting. Participants were stratified according to the result of their mammogram as negative or positive. Mean score of satisfaction was above 2.5 of 4 for all subscales. Women who received positive results were less satisfied with all of subscale factors. Staff interpersonal skills were the most important factor that contributed to general satisfaction. Future efforts such as staff training programme of communication/attitude skills, ensuring privacy and explanation of possible discomfort of the screening would be needed.

Preventive effects of zoledronic acid on bone metastasis in mice injected with human breast cancer cells.

Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incidence of bone metastases than did vehicle-treated nude mice, but these differences were not statistically significant. Only 37.5% of mice treated with zoledronic acid at the time of tumor cell inoculation developed bone metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304). Cell count of apoptosis confirmed by immunohistochemical staining in metastatic bone tissue significantly increased in the zoledronic acid-treated groups compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic tumor cells, which invade soft tissue around the bone, did not show extensive apoptosis; there were no differences between the zoledronic acid-treated and control groups. These results suggest that zoledronic acid increases apoptosis of metastatic breast tumor cells in the bone and could therefore reduce metastatic tumor burden. These results support the use of zoledronic acid to reduce the incidence of bone metastasis in breast cancer.

Prevention of development of postoperative dysesthesia in transforaminal percutaneous endoscopic lumbar discectomy for intracanalicular lumbar disc herniation: floating retraction technique.

BACKGROUND: Transforaminal percutaneous endoscopic lumbar discectomy (PELD) has become a routine surgical procedure because it is minimally invasive. Perioperative complications such as dural injury, infection, nerve root irritation and recurrence can occur not only with PELD, but also with conventional open microsurgery. In contrast, post-operative dysesthesia (POD) due to existing dorsal root ganglion (DRG) injury is a unique complication of PELD. When POD occurs, even if the traversing root has been successfully decompressed, it hinders swift recovery and delays the return to daily routines. Thus, prevention of POD is the key to successful and widespread use of PELD. MATERIAL AND METHODS: From January 2006 to December 2008, 154 patients underwent percutaneous endoscopic discectomy by floating retraction technique at 160 disc levels under local anesthesia. This approach towards the superomedial border of the lower pedicle and the cannula can be placed by gentle retraction of the root with perineural fat instead of direct compression of dorsal root ganglion. The clinical outcomes were assessed using the Visual Analogue Scale (VAS, 0-10 point) for radicular pain and low back pain, and using the Oswestry Disability Index (ODI) for functional status. Perioperative complications and recurrence were reviewed. RESULTS: The mean age was 45 years, the mean operative time was 36 min and the mean follow-up period was 3.4 years. The mean hospital stay for endoscopic discectomy was 1.8 days. No patient underwent repeated PELD or convert microsurgery by incomplete removal of the ruptured particle. All patients experienced early relief of symptoms, as determined by VAS and ODI. No patient developed POD. 1 patient experienced dural injury. There was 1 case of discitis. The recurrence rate was 1.95% (3 patients). CONCLUSION: Transforaminal percutaneous endoscopic lumbar discectomy for intracanalicular lumbar disc herniation is a safe and effective procedure. The floating retraction technique is recommended to avoid development of POD.

Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors.

BACKGROUND: STEALTH(®) liposomal CKD-602 (S-CKD602), a camptothecin analog, is eliminated by the reticuloendothelial system (RES), which consists of cells, including monocytes. We evaluated the relationship between monocyte and absolute neutrophil counts (ANCs) in the blood and pharmacokinetic disposition of S-CKD602 and nonliposomal CKD-602 (NL-CKD602) in patients. METHODS: As part of a phase I study of S-CKD602 and phase I and II studies of NL-CKD602, the percent decreases in ANC and monocytes at their nadir were calculated. After S-CKD602, the amount of CKD-602 recovered in urine was measured. RESULTS: For S-CKD602 in patients <60 years, the percent decrease in ANC and monocytes were 43 ± 31 and 58 ± 26%, respectively (P = 0.001). For S-CKD602 in patients ≥60, the percent decrease in ANC and monocytes were 41 ± 31 and 45 ± 36%, respectively (P = 0.50). For NL-CKD602 (n = 42), the percent decrease in ANC and monocytes were similar (P > 0.05). For S-CKD602, the relationship between the percent decrease in monocytes and CKD-602 recovered in urine was stronger in patients <60 (R(2) = 0.82), compared with patients ≥60 (R(2) = 0.30). CONCLUSIONS: Monocytes are more sensitive to S-CKD602, compared with neutrophils, and the increased sensitivity is related to the liposomal formulation, not CKD-602. These results suggest that monocytes engulf S-CKD602, which causes the release of CKD-602 from the liposome and toxicity to the monocytes, and that the effects are more prominent in patients <60.

Serum lactoferrin level as a serologic biomarker for allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a very common disease and a risk factor for allergic asthma. The discovery of new biomarkers for the early detection of AR would improve the clinical outcomes and reduce socio-economic burden. We sought to identify a novel serologic marker for detection of AR using a proteomic approach. METHODS: To identify the proteins involved in AR, comparative proteomics was applied using nasal lavage fluids (NLFs) taken before and after a nasal provocation test (NPT) with Dermatophagoides pteronyssinus (Dpt) in a subject with AR sensitized to Dpt. The clinical relevance of the identified proteins was evaluated by ELISA using NLFs and sera from the three study groups: Dpt-sensitive AR; asymptomatic Dpt-sensitive controls; and non-atopic healthy controls. The sensitivities and specificities of the candidate proteins for predicting AR were determined using receiver operating characteristic (ROC) curves. RESULTS: In proteomic analysis, lactoferrin expression was up-regulated after NPT. The validation study using ELISA showed a significantly lower serum lactoferrin level in the AR group than those of the other two groups (P<0.05, respectively). To discriminate between subjects with or without AR, the optimal serum cut-off level of lactoferrin was set at <307 ng/mL using the ROC curve. The sensitivity and specificity for predicting AR were 81.4% and 58%. When combined with serum Dpt-specific IgE level, the sensitivity and specificity for predicting AR were 76.7% and 79.2%. CONCLUSION: These results suggest that the serum lactoferrin level is associated with the phenotype of Dpt-sensitive AR, and in combination with the serum Dpt-specific IgE level, may be a potential serologic marker for early detection of AR.