Incidence and risk factors of immediate hypersensitivity reactions associated with low-osmolar iodinated contrast media: a longitudinal study based on a real-time monitoring system

OBJECTIVES: We investigated the incidence of immediate hypersensitivity reaction (HSR) caused by different types of low-osmolar contrast media (LOCM) and cumulative exposure to LOCM. METHODS: This cohort study included all consecutive patients who underwent LOCM-enhanced computed tomography from 2012 through 2014. We assessed 5 LOCM (iobitridol, iohexol, iomeprol, iopamidol, and iopromide). All patients were monitored for adverse events, and new symptoms and signs were recorded in real time using the Contrast Safety Monitoring and Management System (CoSM2oS). RESULTS: The overall incidence of immediate HSR to LOCM was 0.97% (2004 events resulting from 205 726 exposures). Incidence differed significantly depending on whether the patient had a previous history of HSR to LOCM (0.80% in patients with no history and 16.99% in patients with a positive history of HSR to LOCM, P=.001). The incidence of HSR to individual LOCM ranged from 0.72% (iohexol) to 1.34% (iomeprol), although there were no significant differences across the 5 LOCM. A longitudinal analysis demonstrated that the incidence of HSR increased gradually with more frequent previous exposure to LOCM (HR=2.006 [95%CI, 1.517-2.653], P<.001). However, this cumulative increase in risk was observed in patients who had experienced HSR to LOCM, but not in those who had not. CONCLUSION: The incidence of HSR did not differ significantly across the 5 LOCM assessed in the study. Repeated exposure to LOCM did not increase the risk of HSR among patients who had never experienced HSR to LOCM

OBJETIVOS: Estudio de la incidencia de reacciones de hipersensibilidad inmediata frente a diferentes medios de contraste de baja osmolaridad, así como la incidencia global de dichas reacciones con estos contrastes yodados. MÉTODOS: Estudio de cohortes en el que se incluyó de forma consecutiva a todos los pacientes a los que se realizó TAC con contraste yodados de baja osmolaridad durante los años 2012 a 2014. Se emplearon 5 contrastes yodados: iobitridol, iohexol, iomeprol, iopamidol, y iopromide. En todos los pacientes se valoró la presencia de efectos adversos. La aparición de cualquier síntoma fue registrada en el mismo momento de su aparición en el Contrast Safety Monitoring and Management System (CoSM2oS) en tiempo real. RESULTADOS: La incidencia global de reacciones de hipersensibilidad inmediata a medios de contraste yodados de baja osmolaridad fue de 0,97% (2.004 reacciones en 205.726 exploraciones con contraste). La incidencia fue significativamente mayor en los pacientes con historia previa de reacción adversa (16,99%) frente a tan solo 0,80% en los pacientes sin historia previa de reacción (p=.001). La incidencia de estas reacciones osciló desde el 0,72% con iohexol al 1,34% con iomeprol, sin alcanzar diferencias significativas entre los cinco contrastes. Un análisis longitudinal mostró que la incidencia de reacciones inmediatas de hipersensiblidad se incrementa de forma gradual en los pacientes con historia de reacciones previas con medios de contraste yodados (CR=2,006 (1.517-2.653), p<.001). este incremento solo se observaba en los pacientes con historia de reacciones previas, pero no en los sujetos sin historia previa de estas reacciones. CONCLUSIÓN: La incidencia de las reacciones de hipersensibilidad inmediata no fue significativamente diferente entre ninguno de los 5 contrastes utilizados en el estudio. Exposiciones repetidas a estos medios de contraste no aumentan el riesgo de este tipo de reacciones de hipersensibilidad inmediata en los pacientes que no habían presentado previamente este tipo de reacciones

Randomised trial comparing forced-air warming to the upper or lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position.

BACKGROUND: In the supine position, forced-air warming is more effective on the lower body than on the upper body to prevent intraoperative hypothermia. However, it is unknown in the lateral decubitus position. We thus compared forced-air warming on the upper and lower bodies in the lateral position. METHODS: Patients (n=123) were randomised to receive forced-air warming on the upper body or lower body during thoracoscopic surgery in the lateral position. We measured the nasopharyngeal temperature at 0, 30, 60, 90, and 120 min after lateral positioning during surgery and the infrared tympanic membrane temperature at 0, 30, 60, 90, and 120 min after surgery. Patients received both upper and lower body warming at a temperature of <35.5°C. The primary outcome was the incidence of intraoperative hypothermia with a temperature of <36.0°C. RESULTS: Intraoperative hypothermia was less frequent with the upper body warming than with the lower body warming {21/62 vs 35/61, risk ratio [95% confidence interval (CI)] 0.6 (0.4-0.9), P=0.011}. The intraoperative temperature was higher with the upper body warming than with the lower body warming at 30 (P=0.002), 60 (P<0.001), and 90 (P<0.001) min after lateral positioning, and the postoperative temperature was higher at 0 (P<0.001) and 30 (P=0.001) min after surgery. Fewer patients received both upper and lower body warming in the upper body warming group than in the lower body warming group during surgery (1 vs 7, P=0.032). CONCLUSIONS: Forced-air warming was more effective on the upper body than on the lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position. CLINICAL TRIAL REGISTRATION: NCT02993666.

On the mechanical behaviour of PEEK and HA cranial implants under impact loading.

The human head can be subjected to numerous impact loadings such as those produced by a fall or during sport activities. These accidents can result in skull fracture and in some complex cases, part of the skull may need to be replaced by a biomedical implant. Even when the skull is not damaged, such accidents can result in brain swelling treated by decompressive craniectomy. Usually, after recovery, the part of the skull that has been removed is replaced by a prosthesis. In such situations, a computational tool able to analyse the choice of prosthesis material depending on the patient's specific activity has the potential to be extremely useful for clinicians. The work proposed here focusses on the development and use of a numerical model for the analysis of cranial implants under impact conditions. In particular, two main biomaterials commonly employed for this kind of prosthesis are polyether-ether-ketone (PEEK) and macroporous hydroxyapatite (HA). In order to study the suitability of these implants, a finite element head model comprising scalp, skull, cerebral falx, cerebrospinal fluid and brain tissues, with a cranial implant replacing part of the skull has been developed from magnetic resonance imaging data. The human tissues and these two biocompatible materials have been independently studied and their constitutive models are provided here. A computational model of the human head under impact loading is then implemented and validated, and a numerical comparison of the mechanical impact response of PEEK and HA implants is presented. This comparison was carried out in terms of the effectiveness of both implants in ensuring structural integrity and preventing traumatic brain injury. The results obtained in this work highlight the need to take into account environmental mechanical considerations to select the optimal implant depending on the specific patient: whereas HA implants present attractive biointegration properties, PEEK implant can potentially be a much more appropriate choice in a demanding mechanical life style. Finally, a novel methodology is proposed to assess the need for further clinical evaluation in case of impact with both implants over a large range of impact conditions.

Clinical impact of BK virus surveillance on outcomes in kidney transplant recipients.

BACKGROUND: The objective of this study was to investigate the clinical impact of BK virus surveillance on graft injury in kidney transplantation. METHODS: BK viremia in kidney transplant recipients was evaluated by use of plasma quantitative polymerase chain reaction. The prevalence of BK viremia and BK virus-associated nephropathy (BKVAN) and the clinical impact of BK viremia on graft outcomes were assessed. RESULTS: This study took place between January 2008 and June 2013. A total of 213 kidney transplant recipients were included. The prevalence of BK viremia and high BK viremia (≥1 × 10(4) copies/mL) was 66.7% (142/213) and 17.4% (37/213), respectively. A diagnosis of BKVAN was confirmed by means of allograft biopsy in 9 patients (4.2%). The estimated glomerular filtration rate after transplantation was similar in both the low BK viremia (<1 × 10(4) copies/mL) and non-BK viremia groups but was significantly lower in the high BK viremia group after 18 months. In receiver operating characteristic curve analysis, the area under the curve value of plasma polymerase chain reaction was 0.980. We found that a viral load >92,850 copies/mL was able to predict BKVAN with 89% sensitivity and 94.6% specificity. The risk factors for viral loads ≥1 × 10(4) copies/mL were cytomegalovirus infection, steroid pulse therapy, and acute rejection. CONCLUSIONS: High BK viremia was associated with poor graft function after kidney transplantation. The serial monitoring of BK viremia in kidney transplant recipients was helpful in predicting BKVAN and might prevent further progression.

Salivary gland scintigraphy in Sjögren's syndrome. Comparison of the diagnostic performance of visual and semiquantitative analysis.

UNLABELLED: The aim of this study was to compare the diagnostic utility of visual versus semi-quantitative analysis of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome (SS). PATIENTS, METHODS: 99mTc-pertechnetate salivary gland scintigraphy was performed in 145 patients (133 women, 12 men) with clinically suspicious SS. The images were interpreted with visual and semiquantitative methods and the diagnostic performances for SS were compared using uptake and excretory functional parameters. RESULTS: In total, 76 patients (52.4%) were finally diagnosed with SS. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis for the diagnosis of SS were 88.2%, 48.6%, 65.1%, 79.1%, and 69.2%, respectively. Semiquantitative values, the area under the ROC curve for uptake ratio and percentage excretion in the right salivary glands were significantly greater than 0.5 (p < 0.05). However, the percentage excretion in the left salivary glands did not show a statistically significant diagnostic ability for SS. The diagnostic ability of visual assessment was greater than that of the semiquantitative method in terms of evaluating uptake and excretory function in the submandibular glands. CONCLUSION: Visual analysis of salivary gland scintigraphy showed greater diagnostic utility than semiquantitative assessment in the diagnosis of SS, especially in the submandibular glands.

Prevalence, awareness, treatment and control of hypertension in adults with diagnosed diabetes: the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).

We evaluated the prevalence, awareness, treatment and control of hypertension in Korean adults with diagnosed diabetes using nationally representative data. Among subjects aged ≥30 years who participated in the Fourth Korea National Health and Nutrition Examination Survey in 2007 and 2008, a total of 745 subjects (336 men and 409 women) with a previous diagnosis of diabetes mellitus were analyzed. The prevalence of hypertension in adults with diagnosed diabetes was 55.5%. The rates of awareness, treatment and control were 88.0, 94.2, and 30.8%, respectively. Compared with the general population, the prevalence of hypertension in adults with diagnosed diabetes was higher in all age groups in both genders. Factors independently associated with a high prevalence of hypertension included being male, increasing age, single, <9 years of education, the presence of chronic kidney disease risk, hypercholesterolemia (≥240 mg dl(-1)) and high body mass index (≥25 kg m(-2)). Regular medical screening was positively associated with hypertension control, whereas a high triglyceride level (≥150 mg dl(-1)) was inversely associated. A high prevalence and a low control rate of hypertension in adults with diagnosed diabetes suggest that stringent efforts are needed to control blood pressure in diabetic patients.

Mycobacterium kansasii pericarditis in a kidney transplant recipient: a case report and comprehensive review of the literature.

Mycobacterium kansasii is the second most common non-tuberculous mycobacteria in kidney transplant recipients (KTRs) and has been reported to cause disseminated infection in KTRs. We report the first case to our knowledge of M. kansasii pericarditis after kidney transplantation in a 54-year-old man. The patient was admitted with a 2-month history of intermittent fever and myalgia, treated with oral prednisolone and mycophenolate mofetil prior to admission. Chest computed tomography showed enlarged mediastinal lymph node and small amount of pericardial effusion. Mediastinoscopic biopsy of mediastinal lymph node revealed reactive hyperplasia, without evidence of granuloma, but acid-fast bacilli stain of pericardial fluid reported positive finding and pericardial fluid culture identified M. kansasii. The patient has been treated successfully with rifabutin-based combination therapy. All available cases of M. kansasii infection in kidney transplant patients and M. kansasii pericarditis in human immunodeficiency virus-infected patients are comprehensively reviewed.

Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients.

BACKGROUND: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. METHODS: We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation. RESULTS: Patients with the CYP3A5*3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of ≥1 CYP3A5*3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5*1 alleles, might be associated with higher tacrolimus dose per kilogram. CONCLUSIONS: The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients.

Successful kidney transplantation after desensitization using plasmapheresis, low-dose intravenous immunoglobulin, and rituximab in highly sensitized patients: a single-center experience.

BACKGROUND: For many highly allosensitized renal transplant candidates, an acceptable donor is never identified, and the patient remains on dialysis indefinitely. In an attempt to ameliorate this situation, several desensitization protocols have been developed that permit positive-crossmatch kidney transplantation. Here, we report our experiences of living donor kidney transplantation in highly sensitized patients. METHODS: We treated seven highly sensitized patients between March 2003 and September 2009. All patients underwent desensitization using pretransplant plasmapheresis (PP) and low-dose intravenous immunoglobulin (IVIG; 100 mg/kg) with rituximab (six patients) or without rituximab (one patient). Demographics, immunologic characteristics of patients, allograft function, acute rejection (AR) episodes, survival, and adverse events were evaluated. RESULTS: Seven patients with positive-crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Their mean age was 51.4 ± 3.3 years. The average number of human leukocyte antigen mismatchs was 3.4 ± 0.5. The mean percent PRA was 41.7% ± 6.1%. Six patients were crossmatch-positive, and one patient was crossmatch-negative but had high PRA levels. The mean follow-up period was 33.2 ± 5.4 months after transplantation. The all patients showed no AR episodes for follow-up period, and the patient and graft survival rates were 100%. The mean serum creatinine concentration at last follow-up was 0.92 ± 0.11 mg/dL. CONCLUSIONS: Our experiences suggest that the combination of PP and low-dose IVIG with or without rituximab may prove effective as a desensitization regimen for positive-crossmatch and/or highly sensitized living donor renal transplant recipients. Further investigations are needed to evaluate the long-term clinical efficacy and safety of this approach.

Isoflurane late preconditioning against myocardial stunning is associated with enhanced antioxidant defenses.

BACKGROUND: We tested the hypothesis that an upregulation of antioxidant proteins [Cu-Zn superoxide dismutase (SOD), Mn SOD, catalase, glutathione peroxidase, and glutathione peroxidase] plays a role in the delayed protection against myocardial stunning produced by isoflurane preconditioning (ISOPC). Findings were compared with late ischemic PC (IPC). METHODS: Fourteen mongrel dogs were chronically instrumented to measure coronary blood flow and myocardial wall thickening (WT) in conscious state. In Group 1, dogs underwent IPC, induced by a 10-min coronary artery occlusion (CAO); after 24 h of reperfusion, they were subjected to a second 10-min ischemia CAO-reperfusion. In Group 2 (ISOPC), dogs inhaled one minimum alveolar concentration (MAC) ISO (1.4% in O(2)) for 60 min, allowed to recover for 24 h, and then subjected to CAO ischemia-reperfusion. Recovery of WT following the initial 10-min CAO in Group 1 served as control response for both ISOPC and IPC. Expression and activity of antioxidant proteins were measured using Western blotting and spectrophotometric techniques, respectively. RESULTS: Two to three hours of reperfusion were required for recovery of WT following either ISOPC or IPC; in contrast, without PC, WT remained markedly reduced (30% below baseline) at this time point and required more than 6 h of reperfusion for recovery. Neither IPC nor ISOPC affected expression of Cu-Zn SOD, Mn SOD, or catalase. However, ISOPC increased activity of Mn SOD (+40%), catalase (+39%), glutathione peroxidase (+37%), and glutathione reductase (+93%) (P < 0.05); IPC had similar effects. CONCLUSION: ISOPC had powerful, delayed anti-stunning effect that was associated with an enhancement of endogenous antioxidant defenses.

Prolonged use of aspirin alters human and rat intestinal cells and thereby limits the absorption of clopidogrel.

Clopidogrel therapy to prevent atherothrombosis faces the challenge of reduced responsiveness. The absorption of clopidogrel is regulated by multidrug-resistance protein 1 (MDR1) in the intestinal epithelium. Given that aspirin induces MDR1 in cancer cells and peripheral blood cells, it may induce MDR1 in intestinal epithelial cells as well, thereby affecting the absorption of clopidogrel. In this study, aspirin treatment induced the expression of MDR1 in human epithelial colorectal (Caco-2) cells in vitro and in rat intestine in vivo, as evidenced by dose-dependent increases in gene, protein, and efflux function. Along with the upregulation of MDR1 proteins by aspirin, clopidogrel absorption was significantly decreased in the aspirin-treated Caco-2 cells and in rat intestine. Our data provide evidence that prolonged use of aspirin may reduce the intestinal absorption of clopidogrel. Further human studies would be necessary to clarify whether these data have any relevance to prevention of stroke or myocardial infarction.

Peripherally acting CB1-receptor antagonist: the relative importance of central and peripheral CB1 receptors in adiposity control.

OBJECTIVE: To investigate whether drugs targeting peripheral cannabinoid-1 (CB1) receptor ameliorate adiposity comparable to central CB1-receptor antagonist or not. MEASUREMENTS: Receptor binding assay and functional assay in vitro. Pharmacokinetic parameters in mice, brain uptake clearance of compounds in rats and antagonism on the CB1-agonist-induced hypothermia in mice. Diet consumption, body weight changes, hepatic gene expression of sterol-regulatory element-binding protein-1 (SREBP-1) and plasma/tissue concentrations of compounds in HF diet-induced obese (HF-DIO) mice after acute and chronic treatment. RESULTS: Compound-1, an SR141716A derivative, is a peripheral CB1-receptor-selective antagonist that is 10 times less potent than SR141716A in in vitro evaluations. Although the plasma concentrations of Compound-1 are five times higher than those of SR141716A, its potency is still 10 times lower than that of SR141716A in reducing the consumption of normal or HF diet by mice. Through evaluations of brain uptake and the effect on CB1-agonist-induced hypothermia, it was verified that the blood-brain barrier (BBB) penetration of Compound-1 is much lower than that of SR141716A. In HF-DIO mice, chronic treatment by Compound-1 showed dose-dependent antiobesity activities, while its brain distribution was very low as compared with that of SR141716A. Compound-1's effective doses for antiobesity activity were just over 30 mg kg(-1). However, Compound-1 completely suppressed the elevated hepatic SREBP-1 expression even at 10 mg kg(-1). CONCLUSION: These results suggest that (1) central CB1 receptors mediate anorectic response of CB1-receptor antagonists and (2) peripheral modulations, including SREBP-1 expression, are not major mechanisms in the antiobesity effects of CB1-receptor antagonists.

The long-term results of simultaneous fixed-bearing and mobile-bearing total knee replacements performed in the same patient.

We compared the results of 146 patients who received an anatomic modular knee fixed-bearing total knee replacement (TKR) in one knee and a low contact stress rotating platform mobile-bearing TKR in the other. There were 138 women and eight men with a mean age of 69.8 years (42 to 80). The mean follow-up was 13.2 years (11.0 to 14.5). The patients were assessed clinically and radiologically using the rating systems of the Hospital for Special Surgery and the Knee Society at three months, six months, one year, and annually thereafter. The assessment scores of both rating systems pre-operatively and at the final review did not show any statistically significant differences between the two designs of implant. In the anatomic modular knee group, one knee was revised because of aseptic loosening of the tibial component and one because of infection. In addition, three knees were revised because of wear of the polyethylene tibial bearing. In the low contact stress group, two knees were revised because of instability requiring exchange of the polyethylene insert and one because of infection. The radiological analysis found no statistical difference in the incidence of radiolucent lines at the final review (Student's t-test, p = 0.08), most of which occurred at tibial zone 1. The Kaplan-Meier survivorship for aseptic loosening of the anatomic modular knee and the low contact stress implants at 14.5 years was 99% and 100%, respectively, with a 95% confidence interval of 94% to 100% for both designs. We found no evidence of the superiority of one design over the other at long-term follow-up.

Long-term survivorship of the Charnley Elite Plus femoral component in young patients.

We studied prospectively the long-term results of the Charnley Elite-Plus femoral stem in 184 consecutive young patients (194 hips). There were 130 men and 54 women with a mean age of 49.1 years (21 to 60). The predominant diagnosis was osteonecrosis of the femoral head (63.6%, 117 patients). Clinical and radiological evaluation was undertaken at each follow-up. The mean follow-up was 11.2 years (10 to 12). The mean pre-operative Harris hip score was 43.4 (12 to 49) which improved to 91 (59 to 100) at the final follow-up. The survival of the femoral stem at 12 years was 99% with revision as the end-point. The mean annual linear wear of the polyethylene liner was 0.17 mm (0.13 to 0.22). The prevalence of acetabular osteolysis was 10.8% (21 hips) and osteolysis of the calcar femorale 12.9% (25 hips). A third-generation cementing technique, accurate alignment of the stem and the use of a 22 mm zirconia head were important factors in the prevention of aseptic loosening of the Elite Plus femoral stem in these high-risk young patients.

Alignment and orientation of the components in total knee replacement with and without navigation support: a prospective, randomised study.

Bilateral sequential total knee replacement was carried out under one anaesthetic in 100 patients. One knee was replaced using a CT-free computer-assisted navigation system and the other conventionally without navigation. The two methods were compared for accuracy of orientation and alignment of the components. There were 85 women and 15 men with a mean age of 67.6 years (54 to 83). Radiological and CT imaging was carried out to determine the alignment of the components. The mean follow-up was 2.3 years (2 to 3). The operating and tourniquet times were significantly longer in the navigation group (p < 0.001). There were no significant pre- or post-operative differences between the knee scores of the two groups (p = 0.288 and p = 0.429, respectively). The results of imaging and the number of outliers for all radiological parameters were not statistically different (p = 0.109 to p = 0.920). In this series computer-assisted navigated total knee replacement did not result in more accurate orientation and alignment of the components than that achieved by conventional total knee replacement.

Changes in the bone mineral density in the acetabulum and proximal femur after cementless total hip replacement: alumina-on-alumina versus alumina-on-polyethylene articulation.

Our aim in this prospective study was to compare the bone mineral density (BMD) around cementless acetabular and femoral components which were identical in geometry and had the same alumina modular femoral head, but differed in regard to the material of the acetabular liners (alumina ceramic or polyethylene) in 50 patients (100 hips) who had undergone bilateral simultaneous primary total hip replacement. Dual energy X-ray absorptiometry scans of the pelvis and proximal femur were obtained at one week, at one year, and annually thereafter during the five-year period of the study. At the final follow-up, the mean BMD had increased significantly in each group in acetabular zone I of DeLee and Charnley (20% (15% to 26%), p=0.003), but had decreased in acetabular zone II (24% (18% to 36%) in the alumina group and 25% (17% to 31%) in the polyethylene group, p=0.001). There was an increase in the mean BMD in zone III of 2% (0.8% to 3.2%) in the alumina group and 1% (0.6% to 2.2%) in the polyethylene group (p=0.315). There was a decrease in the mean BMD in the calcar region (femoral zone 7) of 15% (8% to 24%) in the alumina group and 14% (6% to 23%) in the polyethylene group (p<0.001). The mean bone loss in femoral zone 1 of Gruen et al was 2% (1.1% to 3.1%) in the alumina group and 3% (1.3% to 4.3%) in the polyethylene group (p=0.03), and in femoral zone 6, the mean bone loss was 15% (9% to 27%) in the alumina group and 14% (11% to 29%) in the polyethylene group compared with baseline values. There was an increase in the mean BMD on the final scans in femoral zones 2 (p=0.04), 3 (p=0.04), 4 (p=0.12) and 5 (p=0.049) in both groups. There was thus no significant difference in the bone remodelling of the acetabulum and femur five years after total hip replacement in those two groups where the only difference was in the acetabular liner.

Development of mesophase pitch derived mesoporous carbons through a commercially nanosized template.

Mesoporous carbons (MCs) with a high surface area (up to 900 m2/g), large pore volume (up to 2.1 cm3/g), high mesopore ratio (94%), and high yield (70%) were successfully prepared from an AR mesophase pitch, using a commercially nanosized silica template. The removal of the template provided some larger mesopores of 25-50 nm (pore I) with a surface area of ca. 300 m2/g, while the successive carbonization opened the closed pores within the carbon body to give smaller mesopores of 2-10 nm (pore II) with a similar surface area. During the carbonization of pitch precursor, the evaporation of volatile components swells the carbon to introduce the second mesopores among the domains and even microdomain units because of their rearrangements and overlappings in the process. The addition of iron salt with the silica template resulted in a remarkable increase of the surface area (ca. 300 m2/g) by introducing mesopores of 3-5 nm. The resultant MCs maintained some graphitizable natures derived from the anisotropic precursor. Their graphitization at 2400 degrees C provided the graphitic structure with large surface areas (270-460 m2/g) and mesoporosity.

Upregulation of rat Ccnd1 gene by exendin-4 in pancreatic beta cell line INS-1: interaction of early growth response-1 with cis-regulatory element.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effect of exendin-4 on the expression of cyclin D1 gene (Ccnd1), which is critical in regulating the progression of the cell cycle in INS-1 cells. MATERIALS AND METHODS: INS-1 cells were stimulated with exendin-4 (10 nmol/l). Transient transfection and luciferase reporter assays were performed to measure promoter activities of rat Ccnd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays were used to examine the binding of transcription factors to sites responsive to exendin-4 in vitro and in vivo, respectively. RESULTS: Exendin-4 increased both Ccnd1 mRNA and its protein levels in a time-dependent manner. The region from -174 to +130 of the promoter was found to contain cis-regulatory elements responsible for exendin-4-mediated gene induction. Early growth response-1 (EGR1) protein was bound to the region from -153 to -134, which includes the putative EGR1 binding site (5'-CACCCCCGC-3'). Moreover, exendin-4 recruited EGR1 protein to the promoter in vivo. CONCLUSIONS/INTERPRETATION: These findings suggest that exendin-4 activates Ccnd1 transcription through induction of EGR1 binding to a cis-regulatory element between -153 and -134 on the rat Ccnd1 promoter. These results provide an important indication that exendin-4 is a growth factor regulating beta cell proliferation.

Carbonization of waste PVC to develop porous carbon material without further activation.

Efficient removal of chlorine from PVC achieved by two-stage heat-treatment (280 and 410 degrees C) provided chlorine-free isotropic pitch containing additive. The pitch was stabilized and carbonized into porous carbons with surface areas of approximately 300 m2/g. Resultant porous carbons showed three pore structures of supermicropore, micropore and mesopore. The generation of CO2 from the decomposition of the CaCO3 additive in waste PVC is responsible for the development of porous structures. The surface area of the carbonized product increased after the removal of CaO.

Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by riluzole.

The action of riluzole, a neuroprotective drug, on cloned delayed rectifier K+ channels (Kv1.5 and Kv3.1) was examined using the whole-cell patch-clamp technique. Riluzole reversibly inhibited Kv1.5 currents in a concentration-dependent manner with an IC50 of 39.69+/-2.37 microM. G-protein inhibitors (pertussis toxin and GDPbetaS) did not prevent this inhibition of riluzole on Kv1.5. No voltage-dependent inhibition by riluzole was found over the voltage range in which channels are fully activated. Riluzole shifted the steady-state inactivation curves of Kv1.5 in a hyperpolarizing direction in a concentration-dependent manner. It accelerated the deactivation kinetics of Kv1.5 in a concentration dependent-manner, but had no effect on the steady-state activation curve. Riluzole exhibited a use-independent inhibition of Kv1.5. The effects of riluzole on Kv3.1, the Shaw-type K+ channel were also examined. Riluzole caused a concentration-dependent inhibition of Kv3.1 currents with an IC50 of 120.98+/-9.74 microM and also shifted the steady-state inactivation curve of Kv3.1 in the hyperpolarizing direction. Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents in a concentration-dependent manner and interacts directly with Kv1.5 by preferentially binding to the inactivated and to the closed states of the channel.