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Do trunk muscle recruitment patterns in patients with low back pain enhance the stability of the lumbar spine?

A comparative study of trunk muscle recruitment patterns in healthy control subjects and patients with chronic low back pain was conducted. To assess trunk muscle recruitment in patients with low back pain. Conflicting evidence has been reported on the level and pattern of trunk muscle recruitment in patients with low back pain. The disparities can be explained partly by methodologic differences. It was hypothesized that trunk muscle recruitment patterns may be altered in patients with low back pain to compensate for reduced spinal stability. For this study, 16 patients with low back pain and 16 matched control subjects performed slow trunk motions about the neutral posture and isometric ramp contractions while seated upright. Ratios of electromyographic amplitudes and estimated moment contributions of antagonist over agonist muscles and of segmentally inserting muscles over muscles inserting on the thorax and pelvis only were calculated. In addition, model simulations were performed to assess the effect of changes in muscle recruitment on spinal stability. The ratios of antagonist over agonist, and of lumbar over thoracic erector spinae electromyographic amplitude and estimated moment contributions were greater in the patients than in the control subjects. The simulation model predicted that these changes would effectively increase spinal stability.

Trunk muscle recruitment patterns in patients with low back pain are different from those in healthy control subjects. The differences are likely to be functional with respect to enhancement of spinal stability in the patients.

Does glucagon-like peptide-1 receptor agonist liraglutide inhibit endothelin-1 in endothelial cell by repressing nuclear factor-kappa B activation?

The increase in endothelin-1 (ET-1) and the decrease in endothelial nitric oxide synthase (eNOS) both induce vasoconstriction and lead to molecular changes associated with diabetes mellitus and atherosclerosis. Glucagon-like peptide-1 (GLP-1) activation stimulates insulin secretion and may prevent atherosclerosis by increasing eNOS synthesis. However, there is paucity of information on the effect of GLP-1 activation on ET-1 expression. This study was conducted to address this issue. Human umbilical vein endothelial cells (HUVECs) were incubated with different concentrations of liraglutide, a GLP-1 agonist, and the expression of ET-1 and eNOS and activity of NF-κB were measured. Liraglutide, in a concentration-dependent manner, was observed to promote eNOS expression and to inhibit ET-1 expression both at mRNA and protein levels. Liraglutide also inhibited NF-κB phosphorylation and its translocation from cytoplasm to the nucleus. To ascertain the role of NF-κB activation in the altered expression of ET-1 and eNOS, we treated HUVECs with phorbol 12-myristate 13-acetate (PMA). PMA activated NF-κB and reversed the effects of liraglutide on eNOS and ET-1 expression. The effects of PMA on eNOS and ET-1 expression were reproduced in experiments wherein cells were treated with TNF-α. Further, we measured the generation of IL-6, apowerful pro-inflammatory molecule released by endothelial cells, as a measure of cellular function. PMA increased IL-6 generation, and this effect was blocked by liraglutide.

Our observations suggest liraglutide suppresses ET-1 expression by inhibiting the phosphorylation of NF-κB. This mechanism may underlie the potential anti-atherosclerotic effects of GLP-1 agonists. Of note, these effects of liraglutide were seen in an in vitro setting wherein cellular glucose concentrations were elevated.

Does right and left prefrontal transcranial magnetic stimulation at 1 Hz affect mood in healthy volunteers?

Prefrontal repetitive transcranial magnetic stimulation (rTMS) has been used to induce side-specific mood changes in volunteers and patients. To clarify inconsistencies between reports that used different stimulation frequencies, we conducted a controlled study with a low (1 Hz) frequency, comparing left with right-sided stimulation Nineteen healthy volunteers received randomised left or right prefrontal rTMS at a frequency of 1 Hz and 100% of motor threshold in two sessions two weeks apart. There were significant improvements with TMS for performance in the digit symbol substitution and verbal fluency tests, but no change of mood on a number of measures. There was also a reduction of pulse rate after TMS. The only side-specific TMS-effect was on mean arterial pressure, which decreased pressure after left, but not after right prefrontal TMS.

Apart from the unexpected and so far unreplicated effect on mean arterial pressure, there were no side-specific effects on mood in volunteers. It is unlikely that a simple laterality model of mood together with the assumed activating effect of higher and 'quenching' effect of lower stimulation frequency can account for the effects of TMS on mood.

Does [ Treatment result following breast-conserving therapy in primary breast cancer ]?

To evaluate mono-institutional results concerning tumor free survival, overall survival, local tumor control and rate of distant metastasis following breast-conserving therapy. Retrospectively, 274 breast cancer patients who were treated between 1990-1997 in our institution were analysed. The whole breast was homogeneously irradiated (2.0 Gy to 50 Gy), followed by a boost of 10-16 Gy to the tumor bed. Mean follow-up was 55 months. Overall survival, local tumor control and rate of distant metastasis were analysed. Cause-specific survival at 5 years after treatment was 93 %. Within 3 to 60 months following treatment, 18 (7 %) patients suffered from ipsilateral breast recurrence. 24 (9 %) patients developed contralateral carcinoma. Survival from local recurrence (single manifestation) was 78 % at 5 years after treatment, 20 % at 7 years. Occurrence of local failures was significantly correlated to receptor status, contralateral carcinoma, distant metastasis and surgical technique and not to tumor size, margins, grading, nodal status, age or lymphangiosis. 9 % of the patients developed distant metastases, predominantly bone metastases (71 %). Survival from distant metastasis was 64 % at 5 years, 10 % at 7 years. Occurrence of distant metastasis was significantly correlated to grading, tumor size, receptor status, lymphangiosis or local recurrence.

Our institutional results show that tumor free survival, overall survival, local tumor control and distant failure rate achieved by breast conserving therapy are within the range of literature data.

18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature?

Our objective was to evaluate (18)F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). (18)F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. All but 2 patients showed significantly increased (18)F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean +/- SD, 8.2 +/- 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean +/- SD, 9.7 +/- 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase-related tumors were notable in being the most (18)F-FDG-avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P = 0.02). (18)F-FDG PET was superior to (131)I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, (18)F-FDG PET underestimated the extent of the disease, compared with 6-(18)F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain (18)F-FDG uptake since most tumors were highly avid for (18)F-FDG.

(18)F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.

Does smad4-mediated signaling inhibit intestinal neoplasia by inhibiting expression of β-catenin?

Mutational inactivation of adenomatous polyposis coli (APC) is an early event in colorectal cancer (CRC) progression that affects the stability and increases the activity of β-catenin, a mediator of Wnt signaling. Progression of CRC also involves inactivation of signaling via transforming growth factor β and bone morphogenetic protein (BMP), which are tumor suppressors. However, the interactions between these pathways are not clear. We investigated the effects of loss of the transcription factor Smad4 on levels of β-catenin messenger RNA (mRNA) and Wnt signaling. We used microarray analysis to associate levels of Smad4 and β-catenin mRNA in colorectal tumor samples from 250 patients. We performed oligonucleotide-mediated knockdown of Smad4 in human embryonic kidney (HEK293T) and in HCT116 colon cancer cells and transgenically expressed Smad4 in SW480 colon cancer cells. We analyzed adenomas from (APC(Δ1638/+)) and (APC(Δ1638/+)) × (K19Cre(ERT2)Smad4(lox/lox)) mice by using laser capture microdissection. In human CRC samples, reduced levels of Smad4 correlated with increased levels of β-catenin mRNA. In Smad4-depleted cell lines, levels of β-catenin mRNA and Wnt signaling increased. Inhibition of BMP or depletion of Smad4 in HEK293T cells increased binding of RNA polymerase II to the β-catenin gene. Expression of Smad4 in SW480 cells reduced Wnt signaling and levels of β-catenin mRNA. In mice with heterozygous disruption of Apc(APC(Δ1638/+)), Smad4-deficient intestinal adenomas had increased levels of β-catenin mRNA and expression of Wnt target genes compared with adenomas from APC(Δ1638/+) mice that expressed Smad4.

Transcription of β-catenin is inhibited by BMP signaling to Smad4. These findings provide important information about the interaction among transforming growth factor β, BMP, and Wnt signaling pathways in progression of CRC.

Is the presence of mitral annular calcification associated with poor left atrial function?

Mitral annular calcification (MAC) is characterized by calcium and lipid deposition in the annular fibrosa of the mitral valve. MAC is associated with cardiovascular events but little is known of its association with left atrial (LA) function. We prospectively obtained 12-lead electrocardiograms (ECGs) and transthoracic echocardiograms (TTE) on patients scheduled for nonemergent echocardiographic assessment at a tertiary care hospital. MAC was graded as 0 = none, 1 = mild, 2 = moderate, 3 = severe. LA linear and volume measurements (stroke volume, LA passive emptying fraction, LA active emptying fraction and LA kinetic energy) were done specifically in addition to commonly measured TTE parameters. From the 124 considered for the study, 72 patients remained (aged 68+/-18 years; 44% male) after excluding those with poor ECG tracings and/or poor TTE images. Eighteen patients had MAC; mild MAC = 14, moderate MAC = 3, severe MAC = 1. When patients with MAC were compared to those without MAC, no significant difference was noted, except for LA linear dimension index (2.1+/-0.4 vs. 1.9+/-0.3 cm/m(2); P = 0.03). For those with mild and moderate MAC, a trend was noted toward lower LA function with increasing MAC severity. In addition, significant differences were noted between those with and without interatrial conduction delay, where those with such delay had significantly impaired LA stroke volume (9.8+/-3 vs. 19.93+/-4 ml; P<0.0001), LA active emptying fraction (18.83+/-8 vs. 65.71+/-9%; P<0.0001) and LA total/reservoir fraction (39.54+/-6 vs. 75.1+/-6%; P<0.0001).

MAC is associated with increase in LA linear dimension on TTE and may be equally represented with lower overall LA function. Further study in a much larger cohort is warranted to delineate these and other potential associations of MAC.

Does a Total Pleural Covering for Lymphangioleiomyomatosis prevent Pneumothorax Recurrence?

Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence-free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 ± 0.606 episode/month (mean ± SD) before TPC vs. 0.008 ± 0.019 after TPC (P<0.0001). Grade IIIa postoperative complications were found in 13 TPC surgeries (24.1%).

TPC successfully prevented the recurrence of pneumothorax in LAM, was minimally invasive and rarely caused restrictive ventilatory impairment.

Is proteinuria unrelated to the extent of acute acetaminophen overdose : a prospective clinical study?

Acute renal failure is a recognized complication of acute acetaminophen overdose. Its detection depends on rising creatinine concentrations, which is an insensitive method. The present study examined whether proteinuria might correspond with the extent of acute acetaminophen exposure as a possible early marker of renal effects. A prospective case-control study included patients attending the emergency department within 24 hours of acetaminophen ingestion. A urine specimen was collected within 12 hours of hospital attendance for creatinine, albumin, and protein determination. Equivalent 4-hour acetaminophen concentrations were used to indicate drug exposure: mild if >100 g/L (>662 mmol/L), moderate if 100-200 g/L (662-1323 mmol/L), or severe if <200 g/L (<1323 mmol/L). Data are presented as median (interquartile range) and groups compared using Mann Whitney and chi-square tests. Seventy patients were studied (17 men, 53 women), age 37 years (23-45 years). The stated acetaminophen dose was 15 g (8-20 g), and interval between ingestion and presentation was 4.6 hours (4.1-7.9 hours). Urinary albumin concentrations were 8 mg/L (0-12 mg/L) in the mild group, 12 mg/L (5-25 mg/L) in the moderate group, and 11 mg/L (6-22 mg/L) in the severe group. Total protein concentrations were 90 mg/L (50-183 mg/L), 70 mg/L (40 to 130 mg/L), and 110 mg/L (75-205 mg/L), respectively. The proportions of patients who had urine albumin:creatinine ratio >3 mg/mmol were 20.8%, 23.5%, and 21.2%, respectively. None of the patients developed acute renal failure.

No relationship was found between the extent of acute acetaminophen exposure and proteinuria. Further work is required to examine whether urinary protein excretion is altered in patients who subsequently develop acute renal failure following acetaminophen overdose.

Is a disease management programme for patients with diabetes mellitus associated with improved quality of care within existing budgets?

To assess the impact of a disease management programme for patients with diabetes mellitus (Type 1 and Type 2) on cost-effectiveness, quality of life and patient self-management. By organizing care in accordance with the principles of disease management, it is aimed to increase quality of care within existing budgets. Single-group, pre-post design with 2-year follow-up in 473 patients. Substantial significant improvements in glycaemic control, health-related quality of life (HRQL) and patient self-management were found. No significant changes were detected in total costs of care. The probability that the disease management programme is cost-effective compared with usual care amounts to 74%, expressed in an average saving of 117 per additional life year at 5% improved HRQL.

Introduction of a disease management programme for patients with diabetes is associated with improved intermediate outcomes within existing budgets. Further research should focus on long-term cost-effectiveness, including diabetic complications and mortality, in a controlled setting or by using decision-analytic modelling techniques.

Do surface glycosaminoglycans mediate adherence between HeLa cells and Lactobacillus salivarius Lv72?

The adhesion of lactobacilli to the vaginal surface is of paramount importance to develop their probiotic functions. For this reason, the role of HeLa cell surface proteoglycans in the attachment of Lactobacillus salivarius Lv72, a mutualistic strain of vaginal origin, was investigated. Incubation of cultures with a variety of glycosaminoglycans (chondroitin sulfate A and C, heparin and heparan sulfate) resulted in marked binding interference. However, no single glycosaminoglycan was able to completely abolish cell binding, the sum of all having an additive effect that suggests cooperation between them and recognition of specific adhesins on the bacterial surface. In contrast, chondroitin sulfate B enhanced cell to cell attachment, showing the relevance of the stereochemistry of the uronic acid and the sulfation pattern on binding. Elimination of the HeLa surface glycosaminoglycans with lyases also resulted in severe adherence impairment. Advantage was taken of the Lactobacillus-glycosaminoglycans interaction to identify an adhesin from the bacterial surface. This protein, identify as a soluble binding protein of an ABC transporter system (OppA) by MALDI-TOF/(MS), was overproduced in Escherichia coli, purified and shown to interfere with L. salivarius Lv72 adhesion to HeLa cells.

These data suggest that glycosaminoglycans play a fundamental role in attachment of mutualistic bacteria to the epithelium that lines the cavities where the normal microbiota thrives, OppA being a bacterial adhesin involved in the process.

Are the glycemic and insulinemic index values of carbohydrate foods similar in healthy control, hyperinsulinemic and type 2 diabetic patients?

a criticism of glycemic index (GI) is that it does not indicate the insulin response of foods (insulinemic index, II). However, it is unknown if the GI and II values of foods are equivalent in all subjects, a necessary criterion for clinical utility. We compared GI and II values in non-diabetic subjects with fasting-serum-insulin (FSI)<40 pmol/l (healthy control) or with FSI ≥ 40 pmol/l (hyper[I]) and subjects with type 2 diabetes (T2DM), and to see whether GI and II were related to the serum-glucose concentrations, insulin sensitivity, β-cell function and hepatic insulin extraction (HIE) of the subjects.SUBJECTS/ Serum-glucose, -insulin and -C-peptide responses after 50 g available-carbohydrate portions of glucose (tested three times by each subject), sucrose, instant mashed-potato, white-bread, polished-rice and pearled-barley were measured in healthy control (n=9), hyper[I] (n=12) and T2DM (n=10) subjects. Food GI values did not differ significantly among the three subject groups, whereas II values were higher in T2DM (100±7) than healthy controls (78±5) and hyper[I] subjects (70±5) (mean±s.e.m., P=0.05). II was inversely associated with insulin sensitivity (r=-0.66, P<0.0001) and positively related to fasting- and postprandial-glucose (both r=0.68, P<0.0001) and HIE (r=0.62, P=0.0002). In contrast, GI was not related to any of the biomarkers (P>0.05).

The GI is a valid property of foods because its value is similar in healthy control, hyper [I] and T2DM subjects, and is independent of subjects' metabolic status. However, II may depend upon the glycaemic control, insulin sensitivity and HIE of the subjects.

Does miR-206 inhibit non small cell lung cancer cell proliferation and invasion by targeting SOX9?

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been suggested to play an essential role in tumorigenesis. miR-206 functions as a tumor suppressor in several cancers. However, its role in non small cell lung cancer (NSCLC) remains unclear. Expression levels of miR-206 in NSCLC tissues and cell lines were determined by quantitative real-time PCR (qRT-PCR). Then, we investigated the role of miR-206 on NSCLC cell proliferation, migration and invasion. Furthermore, luciferase reporter assay was performed to confirm the target gene of miR-206 and the results were validated in NSCLC cells. In the present study, our results showed that miR-206 was decreased in NSCLC tissues compared with adjacent non-tumor tissues. Forced overexpression of miR-206 significantly inhibited cell proliferation, migration and invasion of NSCLC cells. SOX9 was found to be a target of miR-206. Furthermore, down-regulation of SOX9 by shRNA performed similar effects with overexpression of miR-206.

Our study suggested that miR-206 acts as tumor suppressor in NSCLC partially via targeting SOX9.

Does voluntary exercise promote proliferation and differentiation of adult rat hypothalamus progenitor cells?

To investigate the effect of voluntary exercise on the proliferation and differentiation of hypothalamus progenitor cells in adult rats. Male Wistar rats were divided into voluntary exercise (EX) and sedentary (SE) groups, both of which were further divided into 6 subgroups for observation on days 6, 13, 23, 33, 43 and 53. Bromodeoxyuridine (BrdU) was intraperitoneally injected daily for 5 consecutive days after commencing voluntary exercise, and at the specified time points during voluntary exercise, the rats' brains were removed to observe the numbers of BrdU-positive cells in the hypothalamus. Immunohistochemical analysis showed that the numbers of BrdU-positive cells in the hypothalamus of EX subgroups were significantly greater than those of SE subgroups on days 23, 33, 43 and 53. In EX group, the number of BrdU-positive cells double-stained for a mature neuron marker increased after 43 days of voluntary exercise, which did not occur in SE group.

Long-term voluntary exercise can promote the proliferation of neuronal progenitor cells in the hypothalamus and their differentiation into neurons.

Human menopausal gonadotropin versus highly purified-hMG in controlled ovarian hyperstimulation for in-vitro fertilisation: does purity improve outcome?

To examine and compare the effect of the two commercially available menotropins (highly purified-human menopausal gonadotropin (HP-hMG) and the traditional human menopausal gonadotropin (hMG)) on ovarian stimulation characteristics and in-vitro fertilisation (IVF) cycle outcome. We studied 36 patients undergoing at least two controlled ovarian hyperstimulation cycles for IVF, with the same GnRH-analogue protocols, where one included HP-hMG and the other included hMG. Ovarian stimulation characteristics and outcome were compared between the two groups. Patients in the HP-hMG group achieved significantly higher implantation (20.0% vs. 8.1%, p < 0.03; respectively) and pregnancy rates (47.2% vs. 19.4%, p < 0.009; respectively) compared to the hMG group. Although no in-between group difference was observed in the number of top-quality embryos per patient, the proportion of the total number of top-quality embryos per total number of generated embryos was significantly higher in the HP-hMG group (88/196 vs. 72/204, p < 0.049; respectively) as compared to the hMG group.

Patients undergoing controlled ovarian hyperstimulation for IVF that includes HP-hMG preparations produce significantly higher implantation and pregnancy rates, as compared to the traditional hMG.

Surgeon bias in sentinel lymph node dissection: Do tumor characteristics influence decision making?

Determining sentinel lymph nodes (SLNs) in breast cancer staging involves subjective interpretation by the surgeon. We hypothesized patient and tumor characteristics influence number of SLNs harvested. A single-institution, prospectively collected database was queried for breast cancer patients undergoing SLN surgery (2002-2013) and mean SLN counts were compared. There were 2394 SLN biopsies. Mean number of SLNs per patient for the entire cohort was 2.6. Mean number of SLNs removed was greater for patients ≤50 years (2.9 versus 2.6; p<0.0001). Fewer SLNs were removed with tumors ≤1 cm (2.5 versus 2.6; p = 0.002). Patients with grades 2 or 3 tumors had more SLNs removed than grade 1 (2.6 versus 2.5; p = 0.03). Receipt of neoadjuvant therapy was associated with more SLNs removed (3.0 versus 2.6; p = 0.005).

Number of SLNs removed varies based on risk factors for SLN metastasis or false-negative SLN biopsy.

Does ginkgo suppress atherosclerosis through downregulating the expression of connexin 43 in rabbits?

Ginkgo biloba extract (GBE) EGb761 is widely used for cardiovascular prevention. Here, we investigated the effects of GBE on atherosclerotic lesion development in rabbits with a high-fat diet. Forty New Zealand white male rabbits were randomly divided into four groups. The first two were the normal diet group (C) and the high-fat group (HF). The remaining two groups were those who received a high cholesterol diet supplemented with either the standard drug (simvastatin 2 mg/kg/day) or GBE (3 mg/kg/day). At 12 weeks, histopathological and chemical analyses were performed. Plasma lipid measurement showed that GBE inhibited high-fat diet-induced increase of serum triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) by 59.1% (0.9 ±0.2 4 mmol/l vs. 2.2 ±0.4 mmol/l), 18.2% (31.1 ±1.4 mmol/l vs. 38.0 ±0.4 mmol/l) and 15% (28.9 ±1.3 mmol/l vs. 34.0±1.0 mmol/l), respectively, at 12 weeks (p < 0.01). The en face Sudan IV-positive lesion area of the aorta in the GBE group (51.7 ±3.1%) was significantly lower compared with that in the HF group (88.2 ±2.2%; p < 0.01). The mean atherosclerotic lesion area of the GBE group was reduced by 53.2% compared with the HF group (p < 0.01). Immunohistochemistry and western blot analysis showed that GBE markedly suppressed high-fat diet-induced upregulation of connexin 43 (Cx43) in rabbits (p < 0.01).

Thus, our study revealed that GBE prevented atherosclerosis progress through modulating plasma lipid, suppressing atherosclerotic lesion development, and attenuating the expression of Cx43 protein.

Is transport of premature infants associated with increased risk for intraventricular haemorrhage?

Intraventricular haemorrhages (IVH) greatly impact the outcome of very low birth weight (VLBW) infants. This study examines the correlation between inter-hospital transport and the incidence and severity of IVH in VLBW infants in a large cohort of data. The US National Inpatient Sample Database (NIS) and its KID subportion were analysed for the years 1997-2004. Infants <1500 g were included in the study and were classified into transport and inborn groups. Groups were further classified according to birth weight into <1000 g and 1000-1499 g. IVH and severe IVH (grades 3-4) were compared between groups and subgroups. Adjusted OR for IVH or severe IVH in correlation with inter-hospital transport were calculated using logistic regression models while controlling for clinical and demographic confounders. We examined changing trends of the incidence of IVH, incidence of neonatal transport and OR for IVH in correlation with neonatal transport in VLBW infants over the years. A total of 67 596 VLBW infants were included in the study. Overall incidence of IVH in the sample was 14.7%; the transport group had more IVH compared to inborn group (27.4% vs 13.42%): adjusted OR 1.75 (95% CI 1.64 to 1.86; p<0.001). Severe IVH was higher in the transport group compared to the inborn group (44.1% vs 32.9%); adjusted OR 1.44 (95% CI 1.22 to 1.70, p=0.001). Similar results were demonstrated in weight-based subgroups. There was increasing trends for neonatal transport and for IVH over the years (p<0.001 for both) with no significant change in the OR for IVH in transported infants.

Inter-hospital transport of VLBW Infants is correlated with increased incidence and severity of IVH. This correlation has remained constant over the recent years.

Does propofol prevent lung injury after intestinal ischemia-reperfusion by inhibiting the interaction between mast cell activation and oxidative stress?

Both mast cells and oxidative stress are involved in acute lung injury (ALI) induced by intestinal ischemia-reperfusion (IIR). The aim of this study was to investigate whether propofol could improve IIR-induced ALI through inhibiting their interaction. Repetitive, brief IIR or IIR+compound 48/80 was performed in adult Sprague-Dawley rats pretreated with saline, apocynin or propofol. And their lungs were excised for histology, ELISA and protein-expression measurements 2h after reperfusion. Rats pretreated with saline developed critical ALI 2h after IIR. We found significant elevations in lung injury scores, lung wet/dry ratio and gp91phox, p47phox, intercellular cell adhesion molecule-1 protein expressions and higher level of malondialdehyde, interleukin-6 contents, and myeloperoxidase activities, as well as significant reductions in superoxide dismutase activities, accompanied with increases in mast cell degranulation evidenced by significant increases in mast cell counts, β-hexosaminidase concentrations, and tryptase expression. And the lung injury was aggravated in the presence of compound 48/80. However, pretreated with propofol and apocynin not only ameliorated the IIR-mediated pulmonary changes beyond the biochemical changes but also reversed the changes that were aggravated by compound 48/80.

Propofol protects against IIR-mediated ALI, most likely by inhibiting the interaction between oxidative stress and mast cell degranulation.

Is relationship between sun-protection factor and application thickness in high-performance sunscreen : double application of sunscreen recommended?

High-performance sunscreen protects both healthy consumers and photosensitive patients from strong ultraviolet (UV) exposure. The sun-protection factor (SPF), which indicates the efficacy of UV protection, is determined using a prescribed sunscreen application thickness of 2.0 mg/cm(2). Therefore, users should apply at least 2.0 mg/cm(2) of sunscreen to obtain the level of UV protection expected from a product. In most cases, however, users apply insufficient amounts of sunscreen. To determine the amount of sunscreen applied under specific conditions, and the relationship between application thickness and SPF value in high-performance sunscreen. The amount of applied sunscreen was calculated under practical conditions and conditions that directed a double application. The SPF values of high-performance sunscreen applied at three thicknesses (2.0, 1.0 and 0.5 mg/cm(2)) were determined according to the international SPF testing method. RESULTS. The relationship between SPF value and application thickness correlated in a logarithmic curve. The mean application thickness under practical conditions was approximately 1 mg/cm(2), and directing subjects to use a double application increased the application thickness to nearly 2 mg/cm(2).

Encouraging a double application of sunscreen will help users apply products at a thickness sufficient to achieve expected SPF efficacy. We recommend that guidance on double application of sunscreen should be posted in public locations where sunscreen is likely to be in use.

Does antenatal diagnosis of fetal genotype determine if maternal hyperglycemia due to a glucokinase mutation requires treatment?

In women with hyperglycemia due to heterozygous glucokinase (GCK) mutations, the fetal genotype determines its growth. If the fetus inherits the mutation, birth weight is normal when maternal hyperglycemia is not treated, whereas intensive treatment may adversely reduce fetal growth. However, fetal genotype is not usually known antenatally, making treatment decisions difficult. We report two women with gestational diabetes mellitus resulting from GCK mutations with hyperglycemia sufficient to merit treatment. In both women, DNA from chorionic villus sampling, performed after high-risk aneuploidy screening, showed the fetus had inherited the GCK mutation. Therefore, maternal hyperglycemia was not treated. Both offspring had a normal birth weight and no peripartum complications.

In pregnancies where the mother has hyperglycemia due to a GCK mutation, knowing the fetal GCK genotype guides the management of maternal hyperglycemia. Fetal genotyping should be performed when fetal DNA is available from invasive prenatal diagnostic testing.

Does anti-Xa-guided enoxaparin thromboprophylaxis reduce rate of deep venous thromboembolism in high-risk trauma patients?

Appropriate prophylaxis against venous thromboembolism (VTE) remains undefined. This study evaluated an anti-Xa-guided enoxaparin thromboprophylaxis (TPX) protocol on the incidence of VTE in high-risk trauma patients based on Greenfield's Risk Assessment Profile (RAP) score. This is a retrospective observational study of patients admitted to a trauma intensive care unit over a 12-month period. Patients were included if they received anti-Xa-guided enoxaparin TPX. Dosage was adjusted to a prophylactic peak anti-Xa level of 0.2 to 0.4 IU/mL. Subgroup analysis was performed on high-risk patients (RAP score ≥10) who received lower-extremity duplex ultrasound surveillance for deep vein thrombosis (DVT). Data are expressed as mean ± SD. Significance was assessed at p < 0.05. One hundred thirty-one patients received anti-Xa-guided enoxaparin TPX. Four patients were excluded for age or acute VTE on admission. Fifty-six patients with RAP score of ≥10 and surveillance duplex evaluations were included in the subgroup analysis with mean age 43 ± 20 years, Injury Severity Score of 25 ± 10, and RAP score of 16 ± 4. Prophylactic anti-Xa levels were initially achieved in 34.6% of patients. An additional 25.2% required 40 to 60 mg twice daily to reach prophylactic levels; 39.4% never reached prophylactic levels. Weight, body mass index, ISS, and RAP score were significantly higher with subprophylactic anti-Xa levels. One patient developed bleeding complications (0.8%). No patient developed intracerebral bleeding or heparin-induced thrombocytopenia.Nine VTE events occurred in the high-risk subgroup, including four DVT (7.1%), all asymptomatic, and five pulmonary emboli (8.9%). The historical rate of DVT in similar patients (ISS 31 ± 12 and RAP score 16 ± 5) was 20.5%, a significant decrease (p = 0.031). Mean chest Abbreviated Injury Scale scores were significantly higher for patients developing pulmonary emboli than DVT, 3.0 ± 1.1 vs. 0.0 (p < 0.001).

Mean chest Abbreviated Injury Scale score was higher in patients developing pulmonary embolism. Increased weight, body mass index, ISS, and RAP score are associated with subprophylactic anti-Xa levels. Anti-Xa-guided enoxaparin dosing reduced the rate of DVT from 20.5% to 7.1% in high-risk trauma patients.

Does orchidectomy increase beta-adrenoceptor activation-mediated neuronal nitric oxide and noradrenaline release in rat mesenteric artery?

A previous study has demonstrated that endogenous male sex hormones do not alter neuronal nitric oxide (NO) release in rat mesenteric artery. However, the regulatory role of endogenous male sex hormones on noradrenaline (NA) release in rat mesenteric artery is not known. The present study was designed to analyze whether endogenous male sex hormones influence the NA release induced by electrical field stimulation (EFS), as well as the possible modification in NA and neuronal NO release by presynaptic beta-adrenoceptor activation. For this purpose, mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used. Basal and EFS-induced neuronal NO and NA release, as well as the contractile effect induced by EFS, was measured. Basal and EFS-induced neuronal NO and NA release were similar in arteries from control and orchidectomized rats. The beta-adrenoceptor agonist clenbuterol did not modify EFS-induced neuronal NO and NA release in arteries from control rats. In contrast, in arteries from orchidectomized animals, clenbuterol increased both neuronal NO and NA release; this increase was prevented by incubation with the beta-adrenoceptor antagonist propranolol. However, the contractile response elicited by EFS was not modified by clenbuterol in either group of rats.

These results show that orchidectomy does not alter the EFS-induced NA release. What is more, activation of presynaptic beta-adrenoceptors does not modify EFS-induced NA and neuronal NO release in arteries from control rats although it increases the release of both neurotransmitters in arteries from orchidectomized rats. Despite these modifications, the EFS-induced contractile response is preserved in arteries from orchidectomized rats.

Do tumor-educated macrophages promote tumor growth and peritoneal metastasis in an orthotopic nude mouse model of human pancreatic cancer?

Macrophages promote tumor growth by stimulating tumor-associated angiogenesis, cancer-cell invasion, migration, intravasation, and suppression of antitumor immune responses. Ten transgenic nude mice, ubiquitously expressing green fluorescent protein (GFP), were injected subcutaneously with the human pancreatic cancer cell line, BXPC3, stably expressing red fluorescent protein (RFP). GFP-expressing macrophages from the GFP mice with the subcutaneous BxPC3-RFP tumor were harvested and defined as "tumor-educated macrophages". Macrophages were also harvested from transgenic GFP mice (n=10) without tumors and identified as "naïve macrophages." The tumor-educated and naïve macrophages were then implanted into BxPC-3-RFP tumor-bearing non-transgenic nude mice and compared for their ability to enhance tumor progression. In the control group, without macrophage injection, the average primary tumor weighed 668 mg and only three mice (30%) developed peritoneal metastases, which averaged 72 mg. The naïve-macrophage group had an average tumor weight of 823 mg (p=0.51) and 50% developed peritoneal metastases, whose weight averaged 975 mg (p=0.029). The group treated with tumor-educated macrophages had an average primary tumor weight of 2095 mg (p=0.001) and 75% of mice developed peritoneal metastases, whose weight averaged 2135 mg (p=0.008).

These results suggest that macrophages influence tumors, and tumors influence macrophages, and tumor-educated promote tumor progression. Tumor-educated macrophages may be a target for therapy of metastatic cancer.

Is pseudomonas aeruginosa cytotoxicity attenuated at high cell density and associated with the accumulation of phenylacetic acid?

P. aeruginosa is known to cause acute cytotoxicity against various human and animal cells and tissues. Intriguingly, however, in this study we noticed that while a low cell density inoculum of P. aeruginosa caused severe cytotoxicity against human lung tissue cell line A549, increasing the cell density of bacterial inoculum led to decreased cytotoxicity. Addition of the supernatants from high density bacterial culture to low cell density inoculum protected the human cells from bacterial cytotoxic damage, suggesting that P. aeruginosa may produce and accumulate an inhibitory molecule(s) counteracting its pathogenic infection. The inhibitor was purified from the stationary-phase culture supernatants of P. aeruginosa strain PAO1 using bioassay-guided high performance liquid chromatography (HPLC), and characterized to be phenylacetic acid (PAA) by mass spectrometry and nuclear magnetic resonance spectroscopy. Microarray analysis revealed that treatment of P. aeruginosa with PAA down-regulated the transcriptional expression of Type III secretion system (T3SS) genes and related regulatory genes including rsmA and vfr, which were confirmed by transcriptional and translational analysis.

Identification of bacterial metabolite PAA as a T3SS-specific inhibitor explains this intriguing inverse cell-density-dependent-cytotoxicity phenomenon as T3SS is known to be a key virulence factor associated with cytotoxicity and acute infection. The findings may provide useful clues for design and development of new strategies to combat this formidable bacterial pathogen.

Does external application of rapamycin-eluting film at anastomotic sites inhibit neointimal hyperplasia in a canine model?

Stenosis at a vascular anastomotic site has been a significant clinical issue. We tested the hypothesis that rapamycin-eluting biodegradable poly L-lactic acid and epsilon-caprolactone copolymer (PLA-CL) film applied externally can inhibit neointimal hyperplasia in a canine vascular anastomosis model. Femoral artery graft interposition was performed in 25 beagles. Beagles were divided into five groups (five in each): graft interposition without PLA-CL film (control); with PLA-CL film only; and PLA-CL containing rapamycin 8 microg, 80 microg, and 800 microg. Orthotopic arterial graft interposition was performed on the left side and vein graft from the ipsilateral femoral vein was interposed on the right. Morphometric and immunochemical analyses were performed at four-week intervals. In arterial graft models, the ratio of intimal area (intimal area divided by the entire vessel area) was significantly reduced in all the three rapamycin-eluting film groups compared with control (0.19, 0.07, 0.05, and 0.38 in 8 microg, 80 microg, 800 microg groups and control, respectively, p < 0.05). In vein graft models, the ratio of intimal area was significantly decreased only in the 800 microg rapamycin group compared with control (0.33 vs 0.54, p < 0.05). Inhibition of neointimal growth was associated with reduced cell proliferation, as evidenced by proliferating cell nuclear antigen immunostaining and diminished alpha-actin positive vascular smooth muscle cells.

Rapamycin-eluting biodegradable PLA-CL film applied externally can inhibit neointimal hyperplasia of arterial and vein grafts in a canine model. The inhibitory effect of rapamycin-eluting film against neointimal growth is more pronounced in the arterial graft than the vein graft.

Is there a stepwise increase in neonatal morbidities according to histological stage (or grade) of acute chorioamnionitis and funisitis?

To test if there is a stepwise difference in neonatal outcomes according to the stage (or grade) of histological inflammatory response in the chorioamniotic membranes and umbilical cords of preterm premature rupture of membranes (PPROM). This retrospective study included singleton pregnancies diagnosed as PPROM and delivered prior to 34 weeks of gestation (n=339). Acute histological chorioamnionitis and funisitis were subdivided into stages (or grade) as defined by Redline et al. Neonatal composite morbidities and mortality were also monitored. Univariate and multivariate analyses were conducted. Increasing stage (or grade) of acute histological chorioamnionitis and funisitis was significantly associated with an earlier gestational age at membrane rupture and delivery. Among neonatal outcomes, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, retinopathy of prematurity, and composite morbidity showed incremental incidence according to increased stage (or grade) of acute chorioamnionitis, while periventricular leukomalacia and necrotizing enterocolitis did not. Only RDS, BPD, and composite morbidity showed similar incremental incidences associated with severity of funisitis stage. However, the incremental trends of each neonatal outcome were found to be nonsignificant by multivariate analysis adjusting confounding variables including gestational age at delivery.

Higher incidences of neonatal morbidity according to increased stage (or grade) of either acute histological chorioamnionitis or funisitis were due to an earlier gestational age at delivery.

Are bradykinin and its metabolite , Arg-Pro-Pro-Gly-Phe , selective inhibitors of alpha-thrombin-induced platelet activation?

Plasma kininogens are selective inhibitors of alpha-thrombin activation of platelets and endothelial cells. In the present study, we localized the alpha-thrombin inhibitory sequence of kininogens and describe its mechanism of action. Bradykinin and an analogue, MKRPPGFSPFRSSRIG, inhibited alpha-thrombin-induced platelet aggregation and secretion with an IC50 of 0.25 and 1 mmol/L and of 0.23 and 0.5 mmol/L, respectively. The minimal inhibitory peptide was RPPGF. Bradykinin and its analogues did not inhibit ADP-, collagen-, U46619-, or SFLLRN-induced platelet activation or the ability of alpha-thrombin to cleave chromogenic substrates, clot fibrinogen, or block alpha-thrombin binding to platelets. Bradykinin, MKRPPGFSPFRSSRIG, and RPPGF abolished alpha-thrombin-induced (1 nmol/L) calcium mobilization. On flow cytometry, bradykinin and MKRPPGFSPFRSSRIG blocked alpha-thrombin from removing the epitope of its cleavage site on the cloned thrombin receptor. Furthermore, peptide RPPGF or high-molecular-weight kininogen prevented alpha-thrombin from cleaving the thrombin receptor peptide, NATLDPRSFLLR, between arginine and serine.

These results indicate that bradykinin and its metabolites are selective antithrombins by preventing alpha-thrombin cleavage of the cloned thrombin receptor between arginine-41 and serine-42. These newly recognized antithrombin peptides, which are termed thrombostatins, contribute to the cardioprotective nature of kinins.

Does sildenafil enhance quality of nocturnal erections in healthy young men?

To assess the effect of sildenafil on nocturnal erectile function (EF) in young healthy volunteers with normal sexual function (SF) according to the International Index of Erectile Function (IIEF) questionnaire. Thirty-three young (mean age 21 +/- 0.3 years; range 18-25) healthy volunteers not taking any medications who had normal SF and an EF domain>26 on the IIEF questionnaire were evaluated. Erectile function was assessed using the RigiScan (Dacomed Corp., MN, USA) during three nights: night 1 = adaptation to the NPT-Rigiscan apparatus, night 2 = baseline recording of eight parameters, and night 3 = recordings after ingestion of sildenafil 100 mg. Data on the number of erections, erection duration, minimal and maximal base tumescence, minimal and maximal tip tumescence, and base and tip rigidity were analysed using anova with repeated measures. A statistically significant improvement in all eight parameters was observed as a result of sildenafil administration: number of erections from 3.1 +/- 0.7 to 4.0 +/- 0.7 (P<0.05), erection time 22 +/- 3.5 to 34.2 +/- 5.9, minimal base tumescence 8.2 +/- 0.8 to 8.7 +/- 0.8, maximal base tumescence 12.1 +/- 0.7 to 14.2 +/- 0.7, base rigidity 75.6 +/- 3.1 to 81.6 +/- 3.6, tip rigidity 70.6 +/- 1.5 to 75.9 +/- 3.1, minimal tip tumescence 5.9 +/- 0.5 to 6.5 +/- 0.6, and maximal tip tumescence 8.6 +/- 0.6 to 11.7 +/- 0.7 (P<0.0001 for each of the last seven parameters). The mean sleep duration, 7.3 hours (range 6.30-9.20 hours), was similar for both nights of recording.

Sildenafil increases the quality and number of nocturnal erections as tested by the NPT-RigiScan in young healthy volunteers with normal EF.

Orthopedic palatal expansion in the treatment of bilateral congenital choanal atresia: an additional tool in the long term follow up of patients?

Rapid Palatal Expansion (RPE) is an orthodontic procedure commonly used to widen the maxilla. Aim of this study is the description of the effects produced by RPE in two patients affected by Bilateral Congenital Choanal Atresia (BCCA) operated in infancy and who were scheduled for a secondary endoscopical surgical correction. The two cases presented were studied through Postero Anterior and Submental Vertex cephalometric x-rays, and TC-Scans pre and 12 months post expansion. Both nasal and choanal widths were increased 12 months post expansion of an amount which was equivalent to 30% of the defective bony width. Endoscopically the expansion of the lumen was more evident given the associated soft tissue improvement. In both cases secondary surgery was avoided.

The cooperation between ENT surgeon and orthodontist may allow for an reduction in the burden of treatment of children affected by BCCA.

Is loss of expression and function of SOCS3 an early event in HNSCC : altered subcellular localization as a possible mechanism involved in proliferation , migration and invasion?

Suppressor of cytokine signaling 3 (SOCS3) is an inducible endogenous negative regulator of signal transduction and activator of transcription 3 (STAT3). Epigenetic silencing of SOCS3 has been shown in head and neck squamous cell carcinoma (HNSCC), which is associated with increased activation of STAT3. There is scarce information on the functional role of the reduction of SOCS3 expression and no information on altered subcellular localization of SOCS3 in HNSCC. We assessed endogenous SOCS3 expression in different HNSCC cell lines by RT-qPCR and western blot. Immunofluorescence and western blot were used to study the subcellular localization of endogenous SOCS3 induced by IL-6. Overexpression of SOCS3 by CMV-driven plasmids and siRNA-mediated inhibition of endogenous SOCS3 were used to verify the role of SOCS3 on tumor cell proliferation, viability, invasion and migration in vitro. In vivo relevance of SOCS3 expression in HNSCC was studied by quantitative immunohistochemistry of commercially-available tissue microarrays. Endogenous expression of SOCS3 was heterogeneous in four HNSCC cell lines and surprisingly preserved in most of these cell lines. Subcellular localization of endogenous SOCS3 in the HNSCC cell lines was predominantly nuclear as opposed to cytoplasmic in non-neoplasic epithelial cells. Overexpression of SOCS3 produced a relative increase of the protein in the cytoplasmic compartment and significantly inhibited proliferation, migration and invasion, whereas inhibition of endogenous nuclear SOCS3 did not affect these events. Analysis of tissue microarrays indicated that loss of SOCS3 is an early event in HNSCC and was correlated with tumor size and histological grade of dysplasia, but a considerable proportion of cases presented detectable expression of SOCS3.

Our data support a role for SOCS3 as a tumor suppressor gene in HNSCC with relevance on proliferation and invasion processes and suggests that abnormal subcellular localization impairs SOCS3 function in HNSCC cells.

Gastroesophageal reflux disease and tympanoplasty surgical outcome: is there a relationship?

To investigate the possible clinical relationship between gastroesophageal reflux disease and the type one tympanoplasty surgical outcomes of adults with chronic otitis media, by using a simple, cost-effective, reliable questionnaire and physical findings. Fifty-two of 147 patients undergoing type one tympanoplasty were studied. Gastroesophageal reflux disease symptoms were evaluated using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease questionnaire. Laryngoscopic physical findings of laryngopharyngeal reflux were evaluated using the Reflux Finding Score. A successful outcome was defined as an intact tympanic membrane. Correlations between the two assessment tool results and the patient's surgical success were calculated. The gastroesophageal reflux disease questionnaire score was significantly higher in patients with unsuccessful tympanic membrane closure (group one) than in patients with successful closure (group two) (p<0.05). The Reflux Finding Score was also significantly higher in group one than group two (p<0.05). There was a significant positive relationship between the gastroesophageal reflux disease questionnaire score and the Reflux Finding Score (p<0.01).

Gastroesophageal reflux disease may be a significant prognostic factor for tympanoplasty failure. Therefore, reflux investigation may be important during the treatment of chronic otitis media, and positive cases may need reflux treatment as well as ear disease treatment.

Does neoadjuvant antiangiogenic therapy with tamoxifen impair gastrointestinal anastomotic repair in the rat?

Antiangiogenic therapy has the potential to moderate tumour and micrometastatic growth. Its use in the perioperative period is attractive but its potential to compromise wound and anastomotic healing is a cause for concern. Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound healing. We hypothesised that tamoxifen would not adversely affect skin wound and gut anastomotic healing. A previously established model of tamoxifen, administered orally at antiangiogenic doses (20 mg/ml arachais oil/day), was used. Animals received two days pretreatment prior to laparotomy and small bowel anastomosis. Treatment was continued until completion of the study. The principal outcome measures are survival, macroscopic wound and anastomotic healing, anastomotic bursting pressure and PVA sponge granuloma hydroxyproline (OHP) content. Tamoxifen treated animals had fewer complications of skin wound healing than controls (4.5% vs. 19.5%; chi(2) 4.65, 1 d.f., P < 0.05). There was no significant difference in adhesion formation or macroscopic complications of anastomotic healing. Anastomotic bursting pressure was greater in tamoxifen treated animals at postoperative day 3 (39 +/- 4.4 vs. 22.5 +/- 3.5 mmHg; P < 0.01) and equal to that of controls on postoperative day 5 (144.4 +/- 9.4 vs. 127.3 +/- 10.9 mmHg; P = ns). Tamoxifen treated animals weighed significantly less than placebo controls from postoperative day 3 with no difference in mortality between groups (chi(2) = 0.06, 1 d.f., P = ns). PVA sponge granuloma OHP content on day 7 was higher in tamoxifen-treated animals (2.93 +/- 0.4 vs. 1.4 +/- 0.4 mg OHP/mg dry sponge weight; P = 0.03).

Antiangiogenic therapy with tamoxifen has no demonstrable adverse effects on wound or anastomotic repair and its perioperative use is compatible with successful early surgical outcomes.

Are postoperative drains necessary with the Limberg flap for treatment of pilonidal sinus?

Different methods for managing pilonidal sinus have been described in the literature. Our purpose was to evaluate the influence of postoperative drainage in Limberg flaps. Forty patients with pilonidal sinus undergoing radical excision and reconstruction with Limberg flap between 1994 and 1996 were evaluated prospectively. After patients were assigned randomly to the two groups, the effects of drains were studied statistically in terms of wound complications, hospital stay, and recurrence rate. Except for two minor transient wound dehiscences, in all cases primary healing was achieved. Early wound complication rate was 7.5 percent and recurrence rate was 2.5 percent for both groups. There was no significant difference between the groups in early wound complications (P>0.05). The length of hospital stay was significantly longer in the drainage group (P<0.001).

We conclude that Limberg flaps with no drains in place will result in shorter hospital stays without deleteriously affecting the surgical results of wide excision and primary closure with well-vascularized tissue.

Does bmi-1 expression predict prognosis in squamous cell carcinoma of the tongue?

The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor c-myc affects cell proliferation and apoptosis, and Snail regulates epithelial-mesenchymal transition. The expression of these markers has been connected to prognosis in many cancer types. Bmi-1, c-myc, and Snail expressions were studied in our material consisting of 73 primarily T1N0M0 oral tongue carcinoma patients. We compared the immunoexpressions of Bmi-1, c-myc, and Snail with clinical parameters including the degree of histological differentiation, tumour size, TNM classification, depth of invasion, and resection margins. In addition, survival analyses were performed, comparing disease-free survival time with the registered protein expression of the markers mentioned above. A significant correlation between Bmi-1 protein expression and recurrence (log-rank test, P=0.005) was detected. Snail and c-myc expression did not correlate with prognosis. Snail expression correlated with histopathological grade (Fisher's exact test, P=0.007) and with the invasion depth of tumours (chi(2)-test, P=0.037).

Negative Bmi-1 immunoexpression might serve as a marker of poor prognosis in oral tongue carcinoma patients.

Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis?

Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Monocyte chemotactic protein-1 (MCP-1) gene expression is altered by an A/G polymorphism (-2518), with the G allele increasing MCP-1 production. Our aim was to determine whether the MCP-1 -2518 A/G polymorphism affects the severity of AP. Seventy-seven consecutive patients and 116 controls were evaluated. The A/G genotype was evaluated by polymerase chain reaction amplification, restriction fragment length polymorphism, and DNA sequencing. MCP-1 serum levels were quantified using a fluorescence bead-based immunoassay. Sixty-three of 77 patients had MAP (82%) and 14 of 77 had SAP (18%). Patients with SAP had a significantly greater proportion of the G allele (12 of 14; 86%) than did control subjects (50 of 116; 43%) (odds ratio [OR], 7.9; 95% confidence interval [CI], 1.7-37, P<.003) or MAP patients (29 of 63; 46%) (OR, 7.0; 95% CI, 1.5-34; P<.007). Patients with pancreatitis and AA genotype had a low risk for SAP (OR, .13; 95% CI, .01-.61; P<.003). As predicted by the genotype, the serum MCP-1 levels were significantly higher in the SAP patients when compared with the MAP patients ( P = .002) and they also predicted death.

MCP-1 -2518 G allele is a risk factor for severe AP. MCP-1 serum levels, measured early in the course of AP, appear to be an accurate predictor of severity of acute pancreatitis and death.

Does cell-based gene therapy modify matrix remodeling after a myocardial infarction in tissue inhibitor of matrix metalloproteinase-3-deficient mice?

Cell-based gene therapy can enhance the effects of cell transplantation by temporally and spatially regulating the release of the gene product. The purpose of this study was to evaluate transient matrix metalloproteinase inhibition by implanting cells genetically modified to overexpress a natural tissue inhibitor of matrix metalloproteinases (tissue inhibitor of matrix metalloproteinase-3) into the hearts of mutant (tissue inhibitor of matrix metalloproteinase-3-deficient) mice that exhibit an exaggerated response to myocardial infarction. Following a myocardial infarction, tissue inhibitor of matrix metalloproteinase-3-deficient mice undergo accelerated cardiac dilatation and matrix disruption due to uninhibited matrix metalloproteinase activity. This preliminary proof of concept study assessed the potential for cell-based gene therapy to reduce matrix remodeling in the remote myocardium and facilitate functional recovery. Anesthetized tissue inhibitor of matrix metalloproteinase-3-deficient mice were subjected to coronary ligation followed by intramyocardial injection of vector-transfected bone marrow stromal cells, bone marrow stromal cells overexpressing tissue inhibitor of matrix metalloproteinase-3, or medium. Functional, morphologic, histologic, and biochemical studies were performed 0, 3, 7, and 28 days later. Bone marrow stromal cells and bone marrow stromal cells overexpressing tissue inhibitor of matrix metalloproteinase-3 significantly decreased scar expansion and ventricular dilatation 28 days after coronary ligation and increased regional capillary density to day 7. Only bone marrow stromal cells overexpressing tissue inhibitor of matrix metalloproteinase-3 reduced early matrix metalloproteinase activities and tumor necrosis factor alpha levels relative to medium injection. Bone marrow stromal cells overexpressing tissue inhibitor of matrix metalloproteinase-3 were also more effective than bone marrow stromal cells in preventing progressive cardiac dysfunction, preserving remote myocardial collagen content and structure, and reducing border zone apoptosis for at least 28 days after implantation.

Tissue inhibitor of matrix metalloproteinase-3 overexpression enhanced the effects of bone marrow stromal cells transplanted early after a myocardial infarction in tissue inhibitor of matrix metalloproteinase-3-deficient mice by contributing regulated matrix metalloproteinase inhibition to preserve matrix collagen and improve functional recovery.

Does anterior elevation map as the screening test for the ablation power of previous myopic refractive surgery?

We classified the Orbscan anterior elevation maps in normal eyes (under myopic, emmetropic and hyperopic conditions) and in those after myopic refractive surgery. We did this classification to demonstrate how Orbscan anterior elevation maps are useful in screening for the existence and extent of previous myopic refractive surgery. Such a classification can help clinicians interpret preoperative and postoperative topographies. We measured for visual acuity and refractive power in 4800 eyes. After a slit-lamp examination, a corneal topography exam was performed with an Orbscan corneal topography system. The eyes were divided into two groups, with Group I representing those who had not had refractive surgery (4438 eyes). Group II included those who had undergone previous refractive surgery to correct myopia (362 eyes). In Group I, the central island type (43.0%) was the most common, followed by the temporal ridge (25.8%), the with-the-rule regular ridge (16.7%), the against-the-rule regular ridge (6.6%), the nasal ridge (4.0%), and the saddle type (2.1%). In Group II, the depressed lake type (69.9%) was most common, followed by the de-centered ablation type (21.3%). The trend line of the postoperative central anterior surface elevation (E) and the ablation power of refractive surgery were calculated. Ablation power of refractive surgery = 0.0047 E + 0.0083

This study demonstrates that it is possible to use Orbscan anterior elevation maps to screen for the extent of previous refractory surgery used in the correction of myopia. This study may also be useful in understanding the shapes of Orbscan anterior elevation maps before and after myopic refractive surgery as well as in determining the degree of ablated myopic refractive power and decentration.

Does dietary beet pulp decrease taurine status in dogs fed low protein diet?

It is known that large dogs who are fed lamb and rice diets are at increased risk to develop taurine-deficiency-induced dilated cardiomyopathy. Since dogs obligatorily conjugate bile acids (BA) with taurine, we determined whether rice bran (RB) or other fibers (cellulose; CL, beet pulp; BP) would affect BA excretion and/or the taurine status of dogs. Eighteen medium/large mixed-breed dogs were given purified diets containing CL, BP, or RB for 12 weeks. Taurine concentrations in plasma and whole blood were significantly decreased at week 12. The BP group, compared to the CL or RB groups, showed significantly lower taurine concentrations in plasma (6.5 ± 0.5 vs 20.4 ± 3.9 and 13.1 ± 2.0 μmol/L, respectively, P < 0.01, mean ± SEM) and in whole blood (79 ± 10 vs 143 ± 14 and 127 ± 14 μmol/L, respectively, P < 0.01), lower apparent protein digestibility (81.9 ± 0.6 vs 88.8 ± 0.6 and 88.1 ± 1.2 %, respectively, P < 0.01), and higher BA excretions (5.6 ± 0.1 vs 3.4 ± 0.5 and 3.4 ± 0.4 μmol/g feces, respectively, P < 0.05) at week 12.

These results do not support the hypothesis that RB is likely to be a primary cause of lamb meal and rice diets, increasing the risk of taurine deficiency in large dogs. However these indicate that BP may contribute to a decrease taurine status in dogs by increasing excretion of fecal BA and decreasing protein digestibility, thus decreasing the bioavailability of sulfur amino acids, the precursors of taurine.

Does osteopontin induce soluble urokinase-type plasminogen activator receptor production and release?

Osteopontin (OPN) and soluble urokinase plasminogen activator receptor (suPAR) have been proposed as markers of disease severity and risk-stratification in infection and inflammation. In breast cancer, OPN and the membrane bound form of urokinase plasminogen activator receptor (uPAR) are functionally related, as OPN-induced cell migration depends on uPAR triggering by urokinase plasminogen activator (uPA). The aim of this study was to prospectively evaluate the kinetic of OPN and suPAR blood levels in patients developing septic shock (SS) compared to those not developing SS, and to investigate the relationships between these two biomarkers in immune cells in vitro. We measured the levels of OPN and suPAR for 15 days in forty-three patients, defined a priory as at risk to develop septic shock. Moreover, we investigated in vitro the effect of recombinant OPN on uPAR and suPAR expression in monocytes. We found that OPN and suPAR levels were directly correlated to each other both at intensive care unit admission and on the day patients met SIRS/sepsis or septic shock criteria. In patients developing septic shock, OPN increased prior to suPAR and was already detectable up to 4 days before the shock development. In vitro, OPN induced suPAR production in monocytes by increasing both uPAR gene expression, and suPAR release from the cell surface.

These data suggest that OPN is partly responsible for the increased plasma levels of suPAR and might be a valuable tool to predict the occurrence of septic shock.

Is infection with Helicobacter pylori associated with protection against tuberculosis?

Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04).

H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

Lymph node harvest after proctectomy for invasive rectal adenocarcinoma following neoadjuvant therapy: does the same standard apply?

Recent reports indicate that neoadjuvant therapy significantly reduces the lymph node harvest of rectal cancer. The aim of this study was to interpret the lymph node harvest in this setting based on the primary tumor response. All patients undergoing proctectomy were included. Three variables were used as indicators of primary tumor response: ypT stage, tumor size, and tumor regression grade. From 1998 to 2007, 237 patients were identified: 157 in the neoadjuvant therapy group and 80 in the nonneoadjuvant therapy group. Neoadjuvant therapy significantly reduced the number of lymph nodes harvested (P = 0.011). Compared with the nonneoadjuvant group, there were significantly fewer lymph nodes in the neoadjuvant early T stage group (P = 0.001), small tumor size group (P = 0.003), and low tumor regression grade group (P<0.001). However, there was no significant difference between the nonneoadjuvant group and the neoadjuvant advanced T stage (P = 0.664), large tumor (P = 0.815), and high tumor regression grade groups (P = 0.566).

The current standard of lymph node harvest should be applied to patients with poorly responding primary tumors after neoadjuvant therapy. However, a new standard may be necessary to define the adequate number of lymph nodes for tumors that respond well to neoadjuvant therapy.

Does a video questionnaire identify upper airway abnormalities in preschool children with reported wheeze?

Accurate characterisation of subjects is essential to interpret data from studies investigating preschool wheezing. To assess whether a video questionnaire (VQ) identifies upper airway abnormalities in preschool children with reported wheeze. Forty three children (median age 17 months, range 3-58) undergoing fibreoptic bronchoscopy for clinical investigation of troublesome noisy breathing at a tertiary centre were studied. Parents were shown a VQ with four clips (wheeze, stridor, and two other upper respiratory noises) and chose the clip(s) resembling their child's main symptom. Doctor observed symptoms, parental reported symptoms, and symptoms identified on VQ were related to bronchoscopy. Thirty subjects had wheeze as the main symptom: 19 had doctor observed wheeze (DOW) and 11 had parental reported wheeze (RW). Parents of two of the subjects with RW identified wheeze alone on VQ and both had normal bronchoscopic findings. Five of the remaining nine subjects with RW had upper airway abnormalities at bronchoscopy. Parents of six subjects with RW identified a noise other than wheeze on VQ; four of these had upper airway abnormalities. Parents of two subjects with RW did not identify a noise on VQ; one had upper airway abnormalities. Of the 19 with DOW, nine parents identified wheeze alone on VQ, and all had a normal upper airway. Parents of nine subjects with DOW identified a noise other than wheeze as an equal or only symptom, (no noise identified in one), and five had upper airway abnormalities.

A VQ helps to identify upper airway abnormalities in preschool children with a history of wheezing.

Carpal tunnel syndrome: are the MR findings a result of population selection bias?

Previous descriptions of MR imaging of carpal tunnel syndrome used limited study populations and volunteers as controls. We reevaluated these descriptions to determine their sensitivity and specificity when applied to a large consecutive clinical series in which the incidence of carpal tunnel syndrome was small. In 196 consecutive wrists for which supplemental axial conventional spin-echo T1-weighted and fast spin-echo T2-weighted images were obtained at 1.5 T with a dedicated wrist coil, 165 studies were available for review. Previously described signs of carpal tunnel syndrome such as proximally increased size, flattening of the median nerve, increased median nerve signal intensity, flexor tenosynovitis, retinacular bowing, decreased deep tendon fat, and deep palmar bursitis were retrospectively and independently evaluated by two observers who were unaware of patient diagnosis. None of the previously described signs was sensitive for the diagnosis of carpal tunnel syndrome. However, specificity was high for retinacular bowing (94%), median nerve flattening (97%), and deep palmar bursitis (95%).

Most previously described MR imaging signs of carpal tunnel syndrome are insensitive and nonspecific. Exceptions include retinacular bowing, median nerve flattening, and deep palmar bursitis, which in our study proved to have specificities greater than or equal to 94%.

Are high urinary ACE2 concentrations associated with severity of glucose intolerance and microalbuminuria?

Angiotensin-converting enzyme 2 (ACE2) plays an important role in glucose metabolism and renal function. However, the relationship between ACE2 and hyperglycemia or microalbuminuria has not been established in humans. We investigated whether urinary ACE2 levels are associated with abnormal glucose homeostasis and urinary albumin excretion. We developed an ELISA for quantifying ACE2 in urine. The ELISA was used to measure urinary ACE2 levels in 621 subjects with: normal glucose tolerance (NGT; n=77); impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=132); and type 2 diabetes mellitus (T2DM, n=412). Insulin resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR) index and urinary albumin excretion by urine albumin-to-creatinine ratio (ACR). Other biochemical and anthropometric parameters were measured. Urinary ACE2 levels were significantly higher in insulin-resistant subjects with IFG, IGT, and T2DM than in the NGT group (P<0.001). Urinary ACE2 concentrations appeared to correlate with HOMA-IR, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein, serum creatinine, urinary ACR, and systolic blood pressure (all P<0.05). After adjustment for impaired renal function and other metabolic parameters, urinary ACE2 concentration was still associated with a higher risk for T2DM (OR 1.80, 95% CI 1.05-3.08, P=0.02). In addition, urinary ACE2 levels were highly predictive of microalbuminuria after adjusting for clinical risk factors (OR 2.68, 95% CI 1.55-4.64, P<0.001).

Our data suggest that the urinary ACE2 level is closely associated with T2DM and is an independent risk factor for microalbuminuria.

Does 16-slice multidetector computed tomography improve stent patency and in-stent restenosis evaluation?

We studied 88 patients (142 stents): 48 with 1.2-mm MDCT, 40 with 0.6-mm MDCT considering accuracy in assessing the vessel lumen, stent patency and intra-stent restenosis. Coronary angiography comprised the gold standard. Occlusion was detected, respectively, in three of 72 versus four of 70 cases. Patency was assessed in all cases. In-stent restenosis was diagnosed in two of eight cases with thin-slice MDCT.

0.6-mm MDCT allows a better visualization of stent lumen and in-stent restenosis versus 1.2-mm MDCT.

Pulmonary embolism diagnosis and mortality with pulmonary CT angiography versus ventilation-perfusion scintigraphy: evidence of overdiagnosis with CT?

The purposes of this study were to determine whether pulmonary emboli diagnosed with pulmonary CT angiography (CTA) represent a milder disease spectrum than those diagnosed with ventilation-perfusion (V/Q) scintigraphy, to determine the trends in incidence and mortality among patients with the diagnosis of pulmonary embolism from 2000 to 2007, and to correlate incidence and mortality trends with imaging modality trends. Diagnoses of pulmonary embolism from 2000 to 2007 at an urban academic medical center were retrospectively identified. Patient data were collected from the hospital database and the Social Security Death Index. Incident diagnoses, type of imaging used, and date of death were documented. Bivariate and multivariate analyses were used to explore the relations between imaging use and the incidence and mortality of pulmonary embolism. Logistic regression analysis was used to estimate the odds of death of pulmonary embolism diagnosed with pulmonary CTA versus V/Q scintigraphy. The cases of 2087 patients (1361 women, 726 men; mean age, 61.8 years) with pulmonary embolism were identified. From 2000 to 2007 the incidence of pulmonary embolism increased from 0.69 to 0.91 per 100 admissions in strong correlation with increased use of pulmonary CTA. There was no change in mortality, but the case-fatality rate decreased from 5.7% to 3.3%. On average, pulmonary emboli diagnosed with pulmonary CTA were one half as lethal as those diagnosed with V/Q scintigraphy (odds ratio, 0.538; 95% CI, 0.314-0.921).

The results of this study are evidence that the shift in imaging from V/Q scintigraphy to pulmonary CTA resulted in increased diagnosis of a less fatal spectrum of pulmonary embolic disease, raising the possibility of overdiagnosis. Outcome-based clinical trials with long-term follow-up would be helpful to further guide management.

Does interleukin 1beta induce gastric epithelial cell matrix metalloproteinase secretion and activation during Helicobacter pylori infection?

and aims: Matrix metalloproteinases (MMPs) are endopeptidases with roles in extracellular matrix remodelling, cell proliferation, and inflammatory processes. We showed previously that Helicobacter pylori infection of human gastric adenocarcinoma (AGS) cells increased epithelial secretion of epithelial MMP-1 and MMP-3 and bacterial secretion of MMP-3-like activity. In the present study, we sought to characterise the role of interleukin (IL)-1beta in H pylori induced secretion of epithelial MMPs. AGS cells were treated with H pylori and/or IL-1beta. Comparable IL-8 secretory responses (approximately 1700 ng/ml) measured by ELISA were induced by 2.0 ng/ml IL-1beta and by H pylori at a multiplicity of infection (MOI) of 50. The same IL-1beta and H pylori concentrations induced comparable increases in AGS cell caseinolytic activity at 60 kDa. MMP-3 monoclonal antibody immunoblots of AGS cell conditioned media detected immunoreactive bands at 71 kDa and 56 kDa. H pylori (MOI=50-100) induced dose dependent increases in both bands whereas IL-1beta (0.2-2 ng/ml) induced dose dependent increases only in the 71 kDa band, which was identified as a MMP-3/TIMP-3 (tissue inhibitor of metalloproteinases 3) heterodimer. AGS/H pylori conditioned media expressed 24 times more MMP-3 activity than AGS/IL-1beta conditioned media. There was a strong interaction between IL-1beta and H pylori on MMP-3 secretion.

We conclude that IL-1beta induces gastric epithelial cell MMP-3 secretion, contributing to epithelial tissue destruction during H pylori infection. However, other bacterial/host factors are needed to mediate the full gastric epithelial cell MMP-3 secretory response induced by H pylori infection.

Does [ Morroniside inhibit H2O2-induced apoptosis in cultured nerve cells ]?

To investigate the effects of morroniside on H2O2-induced apoptosis in nerve cells. Human neuroblastoma cell line SH-SY5Y cells were pre-incubaed with morroniside (1, 10, and 100 micromol x L(-1)) for 24 h prior to exposure to H2O2 (500 micromol x L(-1)) for 18 h. The activity of reactive SOD was measured by a biochemical assay. The expression of caspase-3, caspase-9, Bcl-2 and Bax was determined by Wastern blotting method. Pretreatment of the cells with morroniside (10 and 100 micromol x L(-1)) increasd SOD activity by 14% (P<0.01) and 11% (P<0.05) in comparison with cells exposed only to H2O2. Morroniside (1, 10, 100 micromol x L(-1)) lowered caspase-3 level by 31% (P<0.01), 103% (P<0.001) and 95% (P<0.001), decreased caspase-9 content by 71% (P<0.001), 132% (P<0.001) and 37% (P<0.05), and increasd Bcl-1 level by 88% (P<0.01), 121% (P<0.001) and 60% (P<0.01) respectively but no significant change occurred in Bax level in comparison with cells exposed only to H2O2.

Morroniside has neuroprotection effect against H2O2-induced oxidation injury in nerve cell.

Is ozone air pollution associated with acute myocardial infarction?

Despite the diversity of the studied health outcomes, types and levels of pollution, and various environmental settings, there is substantial evidence for a positive link between urban air pollution and cardiovascular diseases. The objective of this study was to test the associations between air pollutants and the occurrence of acute myocardial infarction (AMI). Pollutant concentrations (SO2, NO2, and O3) were measured hourly as part of the automated air quality network. Since 1985, an AMI registry (the Toulouse MONICA Project) has been collecting data in the southwest of France. All cases of AMI and sudden and probable cardiac deaths are recorded for subjects 35 to 64 years of age. We studied the short-term exposure effect of pollution on the risk of AMI (from January 1, 1997, to June 30, 1999) using a case-crossover design method. We performed a conditional logistic regression analysis to calculate relative risks (RRs) and their 95% CIs. After adjustment for temperature, relative humidity, and influenza epidemics, the RRs (for an increase of 5 microg/m3 of O3 concentration) for AMI occurrence were significant for the current-day and 1-day-lag measurements (RR, 1.05; 95% CI, 1.01 to 1.08; P=0.009; and RR, 1.05; 95% CI, 1.01 to 1.09; P=0.007, respectively). Subjects 55 to 64 years of age with no personal history of ischemic heart disease were the most susceptible to develop an AMI (RR, 1.14; 95% CI, 1.06 to 1.23). NO2 and SO2 exposures were not significantly associated with the occurrence of AMI.

Observational data confirm that short-term O3 exposure within a period of 1 to 2 days is related to acute coronary events in middle-aged adults without heart disease, whereas NO2 and SO2 are not.

Does use of controller medications in patients initiated on a long-acting beta2-adrenergic agonist before and after safety alert?

The utilization of controller medications before initiating a long-acting beta(2)-adrenergic agonist (LABA) before and after the Food and Drug Administration (FDA) alerts is examined. Electronic claims from a health insurer in the Western United States were examined during two distinct identification periods: before FDA alerts (October 1, 2003, through September 30, 2005) and after FDA alerts (December 1, 2005, through September 30, 2006). Identified patients were at least 12 years old, newly initiated on an LABA, and continuously enrolled during the preperiod (six months before the identification date). Previous controller use was defined as a prescription for an inhaled corticosteroid, mast-cell stabilizer, theophylline, leukotriene modifier, or oral or injectable corticosteroid during the preperiod. Overall, 18,115 patients were identified before the alerts and 7,347 after the alerts. Use of a controller before an LABA was observed in 40% of patients with asthma only, 37% with chronic obstructive pulmonary disease (COPD) only, 65% with COPD plus asthma, and 21% with no asthma or COPD diagnosis. Controller use decreased significantly after FDA alerts as compared with before FDA alerts for patients with asthma only (38% versus 41%, p = 0.005) and patients with no asthma or COPD (17% versus 23%, p < 0.0001).

Previous use of a controller medication before initiation of an LABA was observed in 40% of study patients with a diagnosis of asthma, 37% with COPD, 65% with COPD and asthma, and 21% of patients with no diagnosis of asthma or COPD. Use of a controller medication decreased significantly in patients with asthma or no diagnosis of asthma or COPD following alerts issued by FDA regarding the increased risk of asthma-related death in patients receiving LABAs.

Does rocuronium-sugammadex reduce myalgia and headache after electroconvulsive therapy in patients with major depression?

We aimed to compare the effects of succinylcholine and rocuronium-sugammadex on development of myalgia and headache after electroconvulsive therapy (ECT). Forty-five patients undergoing ECT were enrolled in the study. Anesthesia induction was provided with propofol 1 mg/kg intravenously (IV) + succinylcholine 1 mg/kg IV in group S (n = 24) and propofol 1 mg/kg IV + rocuronium 0.3 mg/kg IV in group R (n = 21). Sugammadex 4 mg/kg IV was administered to group R after the motor seizure. The first 3 ECT sessions were evaluated on the basis of time to onset of spontaneous respiration following the induction, time to eye-opening response to verbal stimuli, and visual analog scale (VAS) scores for myalgia and headache at hours 2, 6, 12, and 24 following the ECT for all patients. The times to onset of spontaneous respiration and eye-opening response to verbal stimuli were significantly shorter in all the 3 sessions in group R compared with group S (P<0.002). Myalgia VAS scores at hours 2, 6, and 12 and the headache VAS scores at hours 2 and 6 were significantly higher in group S versus group R (P<0,015).

We concluded that the rates of myalgia and headache after ECT were significantly lower in group R than in group S, and also the awakening time (spontaneous respiration and opening the eyes in response to verbal stimuli) was significantly shorter in group R compared with group S.

Does ethyl glucuronide disclose recent covert alcohol use not detected by standard testing in forensic psychiatric inpatients?

Considerable lives and money could be saved if one could detect early stages of lapsing/relapsing behavior in addicted persons (e.g., in safety-sensitive workplaces) and could disclose harmful drinking in social drinkers. Due to the serious public health problem of alcohol use and abuse worldwide, markers of alcohol use have been sought. Both ethyl glucuronide (EtG) and phosphatidyl ethanol (PEth) appear to have high sensitivity and specificity and a time frame of detection that may elucidate alcohol use not detected by standard testing. Our aim was to assess their potential for detecting recent covert alcohol use under controlled conditions. Thirty-five forensic psychiatric inpatients in a closed ward who had committed a substance-related offense ( section sign 64 StGB), were followed for 12 months. The complete time spectrum of possible alcohol consumption was covered by the complementary use of breath and urinary ethanol (hours), urinary EtG (days), %carbohydrate-deficient transferrin (CDT)/PEth (weeks), and gamma-glutamyltranspeptidase (GGT)/mean corpuscular volume (MCV) (weeks-months). Fourteen of the 146 urine samples examined were positive for EtG. In all EtG-positive cases, patients reported alcohol consumption of between 40 and 200 g of ethanol 12-60 hr prior to testing. Urinary and breath ethanol were positive in only one case. In the blood samples, PEth was not positive in any case and %CDT did not exceed the reference value. Isoelectric focusing showed no abnormal Tf subtypes.

The findings emphasize the diagnostic and therapeutic usefulness, specificity, and sensitivity of EtG as a marker of recent alcohol use. Such a test is needed in numerous settings, including alcohol and drug treatment (to detect lapse/relapse), in safety-sensitive work settings where use is dangerous or in other settings where use may be inappropriate (e.g., such as driving, workplace, pregnancy, or monitoring physicians or other professionals who are in recovery and working), or for testing other groups (such as children or those with medical problems) where alcohol use would be unhealthy or unsafe. The health, social and socioeconomic benefits arising from the future use of these markers is hard to overestimate.

Do negative symptoms of schizophrenia change over time?

Negative symptoms are a core component of schizophrenia which can severely impact quality of life and functional outcomes. These symptoms are understood to be highly stable but this has not been tested in a meta-analysis, despite the wealth of longitudinal data available. A systematic review of the literature was conducted, with eligible studies pooled into a random-effects meta-analysis. Planned meta-regressions were conducted to evaluate the impact of factors known to induce secondary negative symptoms, in addition to other possible sources of heterogeneity. The main analysis included 89 samples from 41 studies, totalling 5944 participants. Negative symptoms were found to significantly reduce in all treatment interventions, including in placebo and treatment as usual conditions, with a medium effect size (ES) present across all study conditions (ES = 0.66, 95% confidence interval 0.56-0.77, I(2) = 94.0%). In a multivariate meta-regression, only the type of scale used was found to significantly influence negative symptom change. No difference in outcome was found between studies that excluded patients with a high level of positive or depressive symptoms, compared to those that did not.

Negative symptoms were found to reduce in almost all schizophrenia outpatient samples. A reduction was found across all conditions, with effect sizes ranging from small to large depending upon the condition type. These findings challenge the convention that negative symptoms are highly stable and suggest that they may improve to a greater extent than what has previously been assumed.

Does early administration of norepinephrine increase cardiac preload and cardiac output in septic patients with life-threatening hypotension?

We sought to examine the cardiac consequences of early administration of norepinephrine in severely hypotensive sepsis patients hospitalized in a medical intensive care unit of a university hospital. We included 105 septic-shock patients who already had received volume resuscitation. All received norepinephrine early because of life-threatening hypotension and the need to achieve a sufficient perfusion pressure rapidly and to maintain adequate flow. We analyzed the changes in transpulmonary thermodilution variables associated with the increase in mean arterial pressure (MAP) induced by norepinephrine when the achieved MAP was ≥65 mm Hg. Norepinephrine significantly increased MAP from 54 ± 8 to 76 ± 9 mm Hg, cardiac index (CI) from 3.2 ± 1.0 to 3.6 ± 1.1 L/min/m2, stroke volume index (SVI) from 34 ± 12 to 39 ± 13 ml/m2, global end-diastolic volume index (GEDVI) from 694 ± 148 to 742 ± 168 ml/m2, and cardiac function index (CFI) from 4.7 ± 1.5 to 5.0 ± 1.6 per min. Beneficial hemodynamic effects on CI, SVI, GEDVI, and CFI were observed in the group of 71 patients with a baseline echocardiographic left ventricular ejection fraction (LVEF) >45%, as well as in the group of 34 patients with a baseline LVEF ≤45%. No change in CI, SVI, GEDVI, or CFI was observed in the 17 patients with baseline LVEF ≤45% for whom values of MAP ≥75 mm Hg were achieved with norepinephrine.

Early administration of norepinephrine aimed at rapidly achieving a sufficient perfusion pressure in severely hypotensive septic-shock patients is able to increase cardiac output through an increase in cardiac preload and cardiac contractility. This effect remained in patients with poor cardiac contractility except when values of MAP ≥75 mm Hg were achieved.

Nerve growth factor and tyrosine kinase A receptor in oral squamous cell carcinoma: is there an association with perineural invasion?

Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is recognized as a significant predictor of outcome. PNI is associated with locoregional recurrence and decreased survival of patients with head and neck SCC. Nerve growth factor (NGF) has been shown to be involved in PNI in several malignancies, including breast, prostate, and pancreatic cancers. We investigated the hypothesis that NGF and its high-affinity receptor tyrosine kinase A (TrkA) are highly expressed in cases of oral SCC that have histologic evidence of PNI. We performed immunohistochemistry on archived oral tongue SCC specimens from the established oral and general pathology databases at the University of California, San Francisco. The following groups were evaluated: 1) 21 T1/T2 oral tongue SCC cases with PNI and 2) 21 T1/T2 oral tongue SCC cases without histologic evidence of PNI. Strong homogeneous cytoplasmic staining for NGF and TrkA was detected in the malignant cells in the PNI-positive group of tumors. In group II (PNI negative) NGF and TrkA were detected in the stroma cells or were very weakly expressed by the malignant cells. We were able to show the presence of NGF and TrkA in the cytoplasm of malignant squamous cells in tumors with histologic evidence of PNI. Immunostaining for NGF (P = .0001) and TrkA (P = .039) was significantly higher in the PNI-positive oral SCC group than in the PNI-negative oral SCC group.

This study shows that oral SCC with evidence of PNI shows increased expression of NGF and TrkA and suggests that NGF and TrkA are involved with the mechanism leading to PNI. Further investigations are warranted to determine the potential for use of NGF and TrkA as candidate biomarkers to predict progression and outcome.

Is low educational performance associated with drunk driving : a 31-year follow-up of the northern Finland 1966 birth cohort?

We studied the relationship between drunk driving offences, school performance and adult educational achievements. Data from the Northern Finland 1966 Birth Cohort were linked with official criminality files and National Education registers. The cohort members were studied prospectively covering the period from pregnancy to 31 years of age. Drunk driving (one to two arrests) and recidivist drunk driving (three or more arrests) were treated as outcome variables and their relation to school performance was studied by cross-tabulation and to adult educational achievements (two levels of education) by logistic regression analysis, adjusting for parental social class and psychiatric morbidity. Drunk drivers had a statistically significantly worse school performance compared with controls. Male cohort members who had remained at the basic educational level had an elevated risk for drunk driving [odds ratio (OR) 3.0, 95% confidence interval (CI) 2.3-3.8]. The corresponding adjusted ORs for recidivist drunk driving and female drunk driving were 8.6 (95% CI 5.1-14.4) and 7.0 (95% CI 3.3-14.8), respectively.

These results are unlikely to be directly causal; however, educational failures seem to be part of the complex causal pathway to drunk driving and even to alcohol-related disorders.

Resting energy expenditure in females with cystic fibrosis: is it affected by puberty?

The aims of this study were to determine the effect of puberty and the menstrual cycle on resting energy expenditure (REE) in females with cystic fibrosis (CF). Cross-sectional study. All participants had measurements of REE, anthropometry and pubertal staging. The measurements in the postmenarche group were carried out both in the follicular and luteal phases of their menstrual cycle. CF outpatient clinic at the Children's Hospital at Westmead. Fifty-six females with CF and pancreatic insufficiency (13 postmenarche) were recruited from the hospital clinic and 63 controls (21 postmenarche) were recruited through families and friends of hospital staff. Females with CF had a higher REE than controls (111.6+/-12.8% of predicted from controls P<0.001). There was a significant effect of menarche on REE with a decrease in the postmenarche -470 kJ/24 h compared with premenarche after adjustment for fat-free mass, fat mass and group (control or CF). There was no difference in REE between the follicular and luteal phases for either CF or controls.

Females with CF had raised REE that appeared to be independent of menarche. This study implies all females with CF and pancreatic insufficiency may need more intensive dietary management, owing to raised REE, to maintain growth and nutritional status, and possibly improve survival.

Posttraumatic contrast-induced acute kidney injury: minimal consequences or significant threat?

Recent enthusiasm for the use of iodinated contrast media and progressive adaption of modern imaging techniques suggests an increased risk of contrast-induced acute kidney injury (CIAKI) in trauma patients. We hypothesized that CIAKI incidence would be higher than that previously reported. A 1-year retrospective review of our prospective database was performed. Low-osmolar, nonionic, iodinated intravascular (IV) contrast was used exclusively. CIAKI was defined as serum creatinine>0.5 mg/dL, or>25% increase from baseline within 72 hours of admission. The association between CIAKI and risk factors was explored. Of 3,775 patients, 1,184 (31.4%) received IV contrast and had baseline and follow-up serum creatinine. Median age was 38 years (range, 18-95 years) and median Injury Severity Score (ISS) was 16. A total of 8% of patients had history of diabetes mellitus. CIAKI was identified in 78 (6.6%). One patient required long-term hemodialysis. In univariable analysis, age>65 years (p=0.01), history of diabetes mellitus (p=0.01), initial creatinine>1.5 mg/dL (p=0.01), ISS≥16 (p=0.04), and initial systolic blood pressure<90 mm Hg (p=0.01) were identified as risk factors for CIAKI. Of note, no association with the dose of IV contrast≥250 mL and CIAKI was identified (p=0.95). A multiple logistic regression model identified higher age, male gender, systolic blood pressure<90 mm Hg, and higher ISS as risk factors for CIAKI. In-hospital mortality was significantly higher in the CIAKI group (9.0% vs. 3.2%, p=0.02). After adjusting for covariates, CIAKI was not significantly associated with in-hospital mortality.

Current trauma management places patients at substantial risk for CIAKI, and risk stratification can be assessed by common clinical criteria. IV contrast dose alone is not an independent associated risk factor. How these data would be extrapolated to an older cohort remains to be determined.

Does high-sensitivity C-reactive protein add prognostic value to the TIMI-Risk Score in individuals with non-ST elevation acute coronary syndromes?

C-reactive protein (CRP) measured at hospital arrival of patients with non-ST elevation acute coronary syndromes (ACS) may add prognostic information to the TIMI-Risk Score. Eighty-six consecutive patients admitted with unstable angina or non-ST-elevation acute myocardial infarction and symptoms onset within the prior 48 h were included. Recurrent cardiovascular events during hospitalization were defined as non-fatal myocardial infarction or death. Serum CRP was measured immediately at hospital arrival and its prognostic value in relation to in-hospital cardiovascular events was tested by the area under the ROC curve and adjusted for TIMI risk predictors by logistic regression analysis. In addition, a CRP modified TIMI-Risk score was created by adding 2 points if CRP greater than the cut-off proposed by the ROC curve analysis. The accuracy of this new score was compared with the usual TIMI-Risk Score. A significant predictive value of CRP in relation to in-hospital cardiovascular events was indicated by an area under the ROC curve of 0.80 (95% CI=0.66 to 0.93, p=0.009). C-reactive protein cut-off point of best prognostic performance was 7.2 mg/l. In the multivariate analysis, increased CRP (>7.2 mg/l) remained a significant predictor of events after adjustment for TIMI risk predictors (OR=14; 95% CI=1.6-121; p=0.018). The area under the ROC curve for the TIMI-Risk Score was 0.87 (95% CI=0.76-0.99, p=0.001). The addition of CRP to the TIMI-Risk Score improved its prognostic value (area under the ROC curve=0.93; 95% CI=0.87-0.99, p<0.001). The additional value of the new score is demonstrated by a higher specificity (86% vs. 63%, p<0.001) and positive predictive value (39% vs. 19%) in relation to the TIMI-Risk Score.

CRP measured at admission of patients with non-ST-elevation acute coronary syndromes adds prognostic information to the TIMI-Risk Score. Additionally, the incorporation of this variable into the TIMI-Risk Score calculation is an effective manner to utilize CRP for risk stratification.

Do significant variations in mortality occur at similarly designated trauma centers?

Mortality rates vary across designated trauma centers (TC), even after controlling for injury severity. Retrospective analysis of state trauma registry data. Designated Level 1 and 2 TCs in 2003 in a large Southwestern state. Adult trauma patients (n = 18,584) treated at 15 designated Level 1 and 2 TCs. Risk-adjusted survival was calculated for each trauma center using logistic regression analysis to adjust for differences in age, sex, race, injury mechanism, and injury severity. The model was developed using half of the study population and validated in the remaining half. It was then applied to the entire study population, with inclusion of TC identification codes. Observed vs Expected survival ratios were then calculated for each TC. Adjusted odds ratios (OR) for survival at each TC were also calculated. Adjusted OR of survival were significantly different from crude OR at 6 of the 14 TCs, underscoring the importance of risk adjustment when performing quality comparisons. One TC performed significantly worse than the others, 8 achieved significantly better survival, and 5 performed the same as the referent. Observed vs Expected ratios demonstrated that one trauma center had significantly worse severity-adjusted outcomes, some were marginal, some performed as well as expected, and none performed better than expectations.

Considerable variations in risk-adjusted mortality rates exist across similarly designated TCs. Such variability in outcomes may reflect variations in quality of care, and reasons for this discrepancy should be explored as the next step in the trauma care quality improvement process.

Increased short- and long-term mortality at low-volume pediatric heart transplant centers: should minimum standards be set?

The relationship between volume and outcome in many complex surgical procedures is well established. No published data has examined this relationship in pediatric cardiac transplantation, but low-volume adult heart transplant programs seem to have higher early mortality. The United Network for Organ Sharing (UNOS) provided center-specific data for the 4647 transplants performed on patients younger than 19 years old, 1992 to 2007. Patients were stratified into 3 groups based on the volume of transplants performed in the previous 5 years at that center: low [<19 transplants, n = 1135 (24.4%)], medium [19–62 transplants, n = 2321(50.0%)], and high [≥63 transplants, n= 1191 (25.6%)]. A logistic regression model for postoperative mortality was developed and observed-to-expected (O:E) mortality rates calculated for each group. Unadjusted long-term survival decreased with decreasing center volume (P<0.0001). Observed postoperative mortality was higher than expected at low-volume centers [O:E ratio 1.39, 95% confidence interval (CI) 1.05–1.83]. At low volume centers, high-risk patients (1.34, 0.85–2.12)--especially patients 1 year old or younger (1.60, 1.07–2.40) or those with congenital heart disease (1.36, 0.94–1.96)--did poorly, but those at high-volume centers did well (congenital heart disease: 0.90, 0.36–1.26; age<1 year: 0.75, 0.51–1.09). Similar results were obtained in the subset of patients transplanted after 1996. In multivariate logistic regression modeling, transplantation at a low-volume center was associated with an odds ratio for postoperative mortality of 1.60 (95% CI, 1.14–2.24); transplantation at a medium volume center had an odds ratio of 1.24 (95% CI, 0.92–1.66).

The volume of transplants performed at any one center has a significant impact on outcomes. Regionalization of care is one option for improving outcomes in pediatric cardiac transplantation.

Are older patients with mechanical heart valves at increased risk?

Controversy exists regarding the use of mechanical valves in older patients. Many authorities believe that the use of anticoagulants in the elderly is associated with an increased risk of warfarin-related complications. Therefore, we compared the results with mechanical valves in older patients to a cohort of younger patients. Aortic (AVR) or mitral valve replacement (MVR) with a mechanical valve was performed in 1,245 consecutive patients who were followed prospectively. They were grouped by age (group 1,<or = 65 years; group 2,>65 years). The study groups consisted of AVR (group 1, 459 patients; group 2, 323 patients) MVR (group 1, 313 patients; group 2, 150 patients). The average age for the groups was: AVR (group 1, 51 years; group 2, 70 years; p = 0.03) and MVR (group 1, 53 years; group 2, 70 years; p = 0.03). For AVR the incidence of thromboembolism was 0.050 (group 1) and 0.038 (group 2) (p = 0.37) and the actuarial freedom from thromboembolism was 83.0%+/-3.0% and 86.5%+/-1.0%, respectively (p = 0.13). The incidence of bleeding after AVR was 0.021 for group 1 and 0.028 for group 2 (p = 0.49). For MVR the incidence of thromboembolism was 0.059 for group 1 and 0.051 for group 2 (p = 0.75) and the actuarial freedom from thromboembolism was 78.8%+/-3.0% and 75.4%+/-8.7%, respectively (p = 0.71). The incidence of bleeding after MVR was 0.020 for group 1 and 0.027 for group 2 (p = 0.62).

Mechanical valves perform well in selected older patients with no increased risk of bleeding or thromboembolism.

Is there equity in long-term healthcare utilization after traumatic brain injury?

To quantify the long-term use of various types of healthcare services in patients with traumatic brain injury and to estimate the relative contribution of predisposing characteristics, enabling factors and health-related needs to determine whether there is equity in healthcare utilization. Cross-sectional study. Seventy-nine non-institutionalized moderate to severe patients with traumatic brain injury (age range 16-67 years). Healthcare use was measured at 3-5 years post-injury. The relative contribution of predisposing characteristics, enabling factors, and health-related needs to the utilization of various types of care was analysed using logistic regression to determine whether there was equity in healthcare utilization. At least one healthcare service was used by 68% of the patients. Health-related needs explained most of the utilization. However, predisposing characteristics were also related to the use of other medical care and supportive care. Patients with a high internal locus of control were more likely to be users of supportive care, and patients with a high locus of control with the physician were more likely to visit medical specialists.

The results suggest that most of our patients who needed care, received care. However, inequity could not be ruled out completely as predisposing characteristics also contributed to some types of healthcare utilization.

Do monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo?

Leukocyte migration through venular walls is a fundamental event during inflammation, but many aspects of this response, including the mechanisms associated with leukocyte migration through the vascular basement membrane (BM) in vivo, are poorly understood. Here we investigated and compared the means by which neutrophils and monocytes migrate through the venular BM. Specifically, as we have previously reported on the existence of neutrophil permissive sites (termed matrix protein low expression regions; LERs) within the venular BM, we have now investigated the role of these sites in monocyte transmigration in vivo. Analysis of CCL2-stimulated mouse cremaster muscles by immunofluorescent staining and confocal microscopy demonstrated that both neutrophils and monocytes use LERs for penetrating venular walls, but independent and distinct mechanisms are used by the 2 cell types. Collectively, (1) neutrophil but not monocyte transmigration led to enlargement of LERs, (2) monocytes showed a greater extent of deformability in migrating through the venular BM, and (3) only extravasated neutrophils were associated with the carriage of laminin fragments.

The findings provide novel insights into mechanisms of leukocyte transmigration by presenting the first in vivo evidence for distinct modes used by neutrophils and monocytes in penetrating the vascular BM.

Is bowel preparation useful before radiography of the renal tract in patients with spinal cord injury?

To assess, in a blinded study, the usefulness of bowel preparation in improving the quality of radiography of the renal tract in patients with spinal cord injury (SCI). Plain abdominal radiographs of 56 patients with SCI were selected; 24 of the patients had received bowel preparation and 32 had not. The films were independently assessed by one radiologist and one urologist unaware of the treatment and identity of the patients. Each film was divided into five regions of interest and scores of 1-4 (1 for least and 4 for best visibility) assigned to each area. In films with a low aggregate visibility score (</= 12), the cause of poor visibility was assessed in relation to faecal residue and gas. The difference between the overall mean visibility score for bowel-prepared and unprepared patients was not statistically significant. In films with poor visibility, gas shadows predominated over bowel shadows in the bowel-prepared group, although this trend was not statistically significant. Of the five areas, the bladder was scored as being the most clearly seen in both groups.

These findings suggest that bowel preparation does not increase the diagnostic value of radiographs of the renal tract in patients with SCI.

Is a polymorphism controlling ORMDL3 expression associated with asthma that is poorly controlled by current medications?

The specific genetic contributions to childhood asthma have been difficult to elucidate. A recent whole-genome association study suggested that single nucleotide polymorphisms at loci controlling the expression of the ORMDL3 gene and others in the neighborhood of the NRG1 and ERO1LB genes might be important. We sought to replicate the associations of these genetic markers with asthma in a large population of asthmatic patients from Scotland and to assess the effect of these variants on asthma outcomes. Using mouthwash-derived DNA and clinical interviews and measurements, we investigated the association of 3 single nucleotide polymorphisms in the candidate genes with susceptibility to asthma in a case-control study and also exacerbations in a group of 1054 patients aged 3 to 22 years. A common C/T polymorphism at a locus controlling ORMDL3 gene expression (rs7216389) was significantly associated with the risk of childhood asthma (P = 1.73 x 10(-12)), with a single copy of the T allele conferring an odds ratio of 1.50 (95% CI, 1.24-1.81) and 2 copies of the T allele conferring an odds ratio of 2.11 (95% CI, 1.71-2.61), respectively. In asthmatic patients the T allele was associated with exacerbations of the condition (P = .008). Polymorphisms at the loci of nearby genes for NRG1 (rs4512342) and ERO1LB (rs10924993) were associated with neither the occurrence of nor exacerbations of asthma.

A common genetic variation at a locus controlling the expression of the ORMDL3 locus increases the susceptibility to asthma and is associated with poor control of the condition in children and young adults.

Does [ 5-azacytidine enhance anti-tumor efficacy of doxorubicin to neuroblastoma cell lines ]?

The loss of caspase-8 expression correlates with unfavorable survival outcomes in neuroblastoma (NB). Caspase-8 gene inactivation is caused by methylation. This study aimed to explore the effect of the demethylation agent 5-azacytidine on caspase-8 expression and whether 5-azacytidine can increase the sensitivity of chemotherapy drug doxorubicin to NB cells. Caspase-8 mRNA expression in NB cell lines (SH-SY5Y cells) was examined by RT-PCR before and after 5-azacytidine treatment. Survival rates of SH-SY5Y cells were detected using MTT analysis and compared among the doxorubicin alone treatment, 5-azacytidine along with doxorubicin treatment, and caspase-8 inhibitor+5-azacytidine+doxorubicin treatment groups. Caspase-8 mRNA was not expressed in untreated SH-SY5Y cell lines. Caspase-8 mRNA expression in SH-SY5Y cells was detectable 3 days after 5-azacytidine treatment, and increased significantly 5 days after 5-azacytidine treatment (P < 0.05). Survival rates of SH-SY5Y cells treated with 5-azacytidine along with different concentrations of doxorubicin (0.05, 0.1,0.25, 0.5 microg/mL) were (77.61 +/- 7.30)%, (57.35 +/- 6.64)%, (46.25 +/- 4.46)% and (35.59 +/- 5.12)%, respectively, which were significantly lower than those treated with doxorubicin alone (94.89 +/- 4.15%, 80.60 +/- 8.50%, 64.48 +/- 4.92% and 52.32 +/- 6.71%) (P < 0.01). Caspase-8 inhibitor pretreatment resulted in an increased survival rate of SH-SY5Y cells (92.95 +/- 3.48%, 78.39 +/- 4.28 %, 62.31 +/- 6.50% and 49.92 +/- 5.77%) compared with the 5-azacytidine+doxorubicin treatment group.

5-azacytidine may enhance anti-tumor efficacy of doxorubicin to NB cell lines, possibly through an up-regulation of caspase-8 mRNA expression.

Do [ Ephedrine and naloxone promote nerve remodeling after cerebral ischemia ]?

To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity in rats after cerebral ischemia/reperfusion injury to explore the possibility of synergistic effect about ephedrine combined with naloxone, promoting the optimum ratio of neural remodeling and its molecular mechanism. A total of 192 healthy adult Sprague-Dawley rats, 220-250 g, were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. Were randomly divided into 8 groups: the rats were intraperitoneally injected with 1.5 mg x kg(-1) x d(-1) ephedrine (ephedrine group), with 0.1, 0.2, 0.3 mg x kg(-1) x d(-1) naloxone (low, moderate and high doses of naloxone groups) , with 1.5 mg x kg(-1) x d(-1) ephedrine + 0.1, 0.2, 0.3 mg x kg(-1) x d(-1) naloxone (ephedrine + low, moderate and high doses of naloxone groups), and with 0.5 mL saline (model group), respectively. At 1-4 weeks following cerebral ischemia, sensorimotor integration in rats was assessed using the beam walking test, brain-derived neurotrophic factor (BDNF) expression was detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery, immunofluorescence method of detecting ischemic hemisphere hippocampal expression, The number of nerve cells apoptosis was detected using TUNEL assay. BWT, BDNF, TUNEL assay results showed three doses of naloxone group had no significant effect, the effects increased together with the quantitative ephedrine, and had the amount-effect relationship, in which ephedrine + high dose of naloxone group the recovery of movement was fastest, BDNF expression in the best and ischemic apoptosis in the hippocampus at least, ischemic injury to the minimum, speed up the process of neural remodeling.

The ephedrine and ephedrine + naloxone groups were accelerated motor function recovery rate in rat after cerebral ischemia, and the promotion of neural remodeling is closely related to the expression of BDNF, inhibit apoptosis in ischemic area, and with the increase of naloxone amount of additives, its role more clearly, the mechanism may be related to the dose of naloxone can significantly inhibit the ischemic area of apoptosis in early cerebral ischemia, so had the positive synergy effect with ephedrine to speed up the formation of neural remodeling.

Does apoptosis-inducing factor ( AIF ) nuclear translocation mediated caspase-independent mechanism involve in X-ray-induced MCF-7 cell death?

Breast cancer is the most common cancer among women and radiotherapy is a conventional therapy following surgery. Previous studies have demonstrated that except the caspase-dependent pathway, caspase-independent pathway is also involved in the cell death responding to irradiation, despite the unclear mechanism. The purpose of the present study was to observe the role of apoptosis-inducing factor (AIF), the first identified caspase-independent molecule, in X-ray-induced breast cancer cell (MCF-7) cell death. In this study, WST-1 assay, DAPI nuclear staining and clonogenic survival assay were used to test the cell response to different treatments; Western blot was used to detect the protein expression; RT-PCR and plasmid transfection were used to observe the role of AIF. X-ray-induced AIF transferred from the mitochondrion to the nucleus. Inhibition of AIF expression reduced X-ray-induced MCF-7 cell death. Further, AIF nuclear translocation is in a caspase-independent manner in this process, but not caspase-dependent manner.

The present study revealed that AIF nuclear translocation proceeded in X-ray-induced MCF-7 cell death in a caspase-independent manner.

Does vascular endothelial growth factor accelerate establishment of a model of hepatic metastasis in Walker-256 tumor-bearing rats?

Animal models of secondary liver cancer are limited by the time required for the development of hepatic metastases. The authors administered vascular endothelial growth factor (VEGF) to stimulate tumor growth in a model of hepatic metastasis. A 0.5 to 1.0 mm³ Walker-256 carcinosarcoma tumor tissue was implanted into the livers of 45 Sprague-Dawley rats, randomly assigned to 3 equal groups to receive daily injections (0.1 mL), for 1 week, of either normal saline (control group), 20 mg/L VEGF (VEGF-20 group) or 40 mg/L VEGF (VEGF-40 group). Tumor growth was assessed by magnetic resonance imaging after 3, 7 and 14 days, and overall survival was recorded. Three days after implantation, no tumors were detected by magnetic resonance imaging in the control group. In contrast, tumors were observed in 50% of rats in the VEGF-20 group and 66.7% of rats in the VEGF-40 group (P < 0.05). By day 7, tumors were detected in 92.8% of rats in the VEGF-20 group, 86.7% of rats in the VEGF-40 group, but only 21.4% of rats in the control group (P < 0.05). Tumor size increased progressively, reaching 1.81 ± 0.08, 2.51 ± 0.12 and 2.67 ± 0.10 cm³ in the control, VEGF-20 and VEGF-40 groups, respectively, 14 days after implantation of tumor tissue. Median survival times were significantly shorter in the VEGF-40 group (15 days) than in the control and VEGF-20 groups (27 and 25, respectively) (both P < 0.05).

Daily VEGF injection (20 mg/L, 1 week) accelerates tumorigenesis without compromising survival, potentially extending the period in which experiments can be conducted in this model.

Do male and female adolescents view their dissatisfaction with body parts in the same way?

(1) To learn how female and male adolescents view their dissatisfaction toward body parts, and (2) learn how gender-related dissatisfaction toward body parts in Thai adolescents differs from those studied in Western countries. The researcher recruited 400 Thai male and female adolescents in Bangkok, attending high school to freshmen level, and ranging from 16-19 years, to participate in this study. Survey questionnaires containing questions related to the research objectives were distributed to each student. In addition, the researcher conducted in-depth follow-up interviews with 40 students to gain insightful data, which were beneficial for the content and percentage result analysis. The findings show that Thai female and male adolescents viewed their dissatisfaction toward body parts differently. Whereas Thai female adolescents viewed their dissatisfied body parts individually and looked at their bodies in detail, Thai male adolescents tended to view their bodies as a whole and describe their dissatisfied body parts as problematic area(s). Moreover, some of the results in this study showed similarity with research conducted in the West. However, there were also differences that can be seen in detail showing a variation on the gender-related dissatisfied body parts names, percentage to each body part/area, and its beautified meanings. Like studies conducted in the West, female adolescents showed greater dissatisfaction toward their bodies and felt more pressure to fix problematic parts than did men.

How females and males view their bodies differently can be linked to greater incidence of dieting and eating disorders in females than in males.

Does exposure to hexachlorobenzene during pregnancy increase the risk of overweight in children aged 6 years?

To determine whether prenatal exposure to hexachlorobenzene (HCB) has potential adverse effects on child's weight and body mass index (BMI) in a general population with no local pollution sources. Starting from mid 1997, all mothers presenting for antenatal exposure in Menorca were recruited. Subsequently, 482 children were enrolled. HCB was measured in cord blood. Weight and height were measured at birth and at age 6.5 years. Children with HCB levels higher than 1.03 ng/mL in cord blood were 1.14 kg (0.38) heavier and had a higher BMI (beta= 0.80 (0.34)) than children with HCB levels lower than 0.46 ng/mL. No statistically significant associations were found in height. Children in the higher exposure group of HCB had an increased risk of 2.5 and 3.0 of being overweight and obese. Children from normal weight mothers also presented an increased risk of having higher BMI with increasing concentrations of HCB in cord serum.

Prenatal exposure to HCB is associated with an increase in BMI and weight at age 6.5 years. Further studies with larger samples and longer follow-up are needed to confirm these results.

Does combination therapy of 15-epi-lipoxin A4 with antibiotics protect mice from Escherichia coli-induced sepsis*?

Inflammation occurs along with infection during sepsis. 15-Epi-lipoxin A4 has protective and resolving effects in experimental models of infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis. Prospective experimental study. University research laboratory. Male C57BL/6 mice. Mice were injected with E. coli to induce peritonitis and were given either 15-epi-lipoxin A4 (1 μg/mouse) or placebo (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days. In addition, we examined the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. coli. Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4 with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi-lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages. Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced the production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages stimulated with live E. coli.

15-Epi-lipoxin A4 combined with antibiotics attenuated systemic inflammation, inhibited bacteria dissemination, and improved survival in E. coli-infected mice. The reduced production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory response. Taken together, these data suggested that 15-epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without exacerbating infection.

Does [ SUCI02 inhibit HER-2/neu receptor tyrosine kinase phosphorylation and growth of HER-2/neu-overexpressing breast cancer cells ]?

Overexpression of HER-2/neu receptor plays a key role in tumorigenesis,progression,prognosis and chemosensitivity of tumors. We found that SUCI02[N-(4-ethoyphenol)-2-hydroxy- acid amide] could inhibit HER2/neu phosphorylation through comprehensive screening. The aim of this study was to examine the effect of SUCI02 on HER-2/neu-overexpressing cancer cell growth. Western blot analysis and immunoprecipitation was used to examine the changes of HER-2/neu receptor tyrosine kinase phosphorylation and protein level. MTT assay was employed to determine the growth inhibition of SUCI02 on the tumor cells. SUCI02 reversibly inhibited tyrosine phosphorylation of HER-2/neu in a dose-dependent manner with half maximal inhibition at a concentration of 4.34 microg/ml without reduced HER-2/neu receptor protein expression. Activation of MAPK and AKT, which were downstream molecules of HER-2/neu-mediated signal transduction pathway, was inhibited after being exposure to SUCI02. In contrast, tyrosine phosphorylation of EGFR was relatively unaffected at the concentrations of SUCI02 up to 40 microg/ml. SUCI02 inhibited cell proliferation of HER-2/neu- overexpressing MDA-MB-453m1 more potent than that of EGFR-overexpressing MDA-MB-468.Their IC(50) values were 1.33 microg/ml and 11.3 microg/ml,respectively.

SUCI02 can inhibit tyrosine phosphorylation of HER-2/neu receptor,cell proliferation of HER-2/neu-overexpressing breast cancer cells preferentially and shut down downstream HER-2/neu signal transduction.

Is upper extremity access for fenestrated endovascular aortic aneurysm repair associated with increased morbidity?

Fenestrated endovascular aortic aneurysm repair (FEVAR) is an alternative to open repair in patients with complex abdominal aortic aneurysms who are neither fit nor suitable for standard open or endovascular repair. Chimney and snorkel grafts are other endovascular alternatives but frequently require bilateral upper extremity access that has been associated with a 3% to 10% risk of stroke. However, upper extremity access is also frequently required for FEVAR because of the caudal orientation of the visceral vessels. The purpose of this study was to assess the use of upper extremity access for FEVAR and the associated morbidity. During a 5-year period, 148 patients underwent FEVAR, and upper extremity access for FEVAR was used in 98 (66%). Outcomes were compared between those who underwent upper extremity access and those who underwent femoral access alone. The primary end point was a cerebrovascular accident or transient ischemic attack, and the secondary end point was local access site complications. The mean number of fenestrated vessels was 3.07 ± 0.81 (median, 3) for a total of 457 vessels stented. Percutaneous upper extremity access was used in 12 patients (12%) and open access in 86 (88%). All patients who required a sheath size >7F underwent high brachial open access, with the exception of one patient who underwent percutaneous axillary access with a 12F sheath. The mean sheath size was 10.59F ± 2.51F (median, 12F), which was advanced into the descending thoracic aorta, allowing multiple wire and catheter exchanges. One hemorrhagic stroke (one of 98 [1%]) occurred in the upper extremity access group, and one ischemic stroke (one of 54 [2%]) occurred in the femoral-only access group (P = .67). The stroke in the upper extremity access group occurred 5 days after FEVAR and was related to uncontrolled hypertension, whereas the stroke in the femoral group occurred on postoperative day 3. Neither patient had signs or symptoms of a stroke immediately after FEVAR. The right upper extremity was accessed six times without a stroke (0%) compared with the left being accessed 92 times with one stroke (1%; P = .8). Four patients (4%) had local complications related to upper extremity access. One (1%) required exploration for an expanding hematoma after manual compression for a 7F sheath, one (1%) required exploration for hematoma and neurologic symptoms after open access for a 12F sheath, and two patients (2%) with small hematomas did not require intervention. Two (two of 12 [17%]) of these complications were in the percutaneous access group, which were significantly more frequent than in the open group (two of 86 [2%]; P = .02).

Upper extremity access appears to be a safe and feasible approach for patients undergoing FEVAR. Open exposure in the upper extremity may be safer than percutaneous access during FEVAR. Unlike chimney and snorkel grafts, upper extremity access during FEVAR is not associated with an increased risk of stroke, despite the need for multiple visceral vessel stenting.

Does hyperbaric oxygenation improve locomotor ability by enhancing neuroplastic responses after cortical ablation in rats?

To investigate whether hyperbaric oxygenation (HBO) can improve the recovery of motor functions in rats after suction ablation of the right sensorimotor cortex. The experimental paradigm implies the following groups: Control animals (C), Control + HBO (CHBO), Sham controls (S), Sham control + HBO (SHBO), Lesion group (L), right sensorimotor cortex was removed by suction, Lesion + HBO (LHBO). Hyperbaric protocol: pressure applied 2.5 atmospheres absolute, for 60 minutes, once a day for 10 days. A beam walking test and grip strength meter were used to evaluate the recovery of motor functions. Expression profiles of growth-associated protein 43 (GAP43) and synaptophysin (SYP) were detected using immunohistochemistry. The LHBO group achieved statistically superior scores in the beam walking test compared to the L group. Additionally, the recovery of muscle strength of the affected hindpaw was significantly enhanced after HBO treatment. Hyperbaric oxygenation induced over-expression of GAP43 and SYP in the neurons surrounding the lesion site.

Data presented suggest that hyperbaric oxygen therapy can intensify neuroplastic responses by promoting axonal sprouting and synapse remodelling, which contributes to the recovery of locomotor performances in rats. This provides the perspective for implementation of HBO in clinical strategies for treating traumatic brain injuries.

Is high level of urokinase-type plasminogen activator a new prognostic marker in patients with gastric carcinoma?

Prognosis of gastric carcinoma is related to invasion and metastasis. Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membrane. The serine protease urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), appear to have a major function in these processes. Recent reports have demonstrated that expression of these proteolytic enzymes is elevated in breast and colon carcinoma and that it can be associated with invasiveness and poor prognosis. Therefore, the authors evaluated whether the expression and activation of uPA and PAI-1 might be of clinical value as a tumor/biologically defined risk factor in patients with gastric carcinoma. Enzyme-linked immunoadsorbent assays were used to test for uPA antigens and PAI-1 in tissue extracts of normal and cancerous tissue from 160 gastric carcinoma patients who were enrolled in the Yonsei Cancer Center Study Group. Both uPA and PAI-1 levels were significantly higher in cancerous tissues than in normal tissues (uPA: 9.4 +/- 8.7 vs. 5.3 +/- 3.1 ng/mg protein cytosol; PAI-1: 10.9 +/- 9.1 vs. 5.8 +/- 2.9 ng/mg protein cytosol), (P < 0.001, respectively). Both high uPA and PAI-1 levels were associated with differentiation of the tumor (P = 0.04 and P = 0.004, respectively), and a high PAI-1 level was associated with lymph node metastasis at an advanced stage (P = 0.003 and P = 0.04, respectively). There was a correlation between the levels of uPA and PAI-1 expression in cancerous tissues (correlation coefficient = 0.57). In univariate analysis, a high level of uPA or PAI-1 was associated with a short relapse free survival, but in multivariate analysis only a high level of uPA was an independent prognostic parameter for a short relapse free survival for gastric carcinoma patients.

These data indicate that uPA is a new independent variable for the identification of high risk gastric carcinoma patients. Therefore, therapy targeting uPA can be applied as a new biologic treatment modality for these individuals.

Is a lower serum level of middle-molecular-weight adiponectin a risk factor for endometrial cancer?

The present study was undertaken to examine the correlation between serum levels of adiponectin isoforms and the risk for endometrial cancer. This retrospective case-control study included 43 Japanese women with endometrial cancer and 62 Japanese women with no history of cancer. Serum levels of total adiponectin and the respective isoforms were determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was performed on the serum levels of total adiponectin and its isoforms, high molecular weight, middle molecular weight, and low molecular weight adiponectins, after adjustment for confounders (age, body mass index, hypertension, and diabetes mellitus). The distribution of body mass index revealed a statistically significant difference between patients and controls (P = 0.001). A statistically significant difference (P < 0.01) was also found in the incidence of diabetes mellitus between the two groups, although there was no significant difference in the incidence of hypertension. In controls, an inverse correlation was observed between body mass index and serum adiponectin levels. However, in patients, an inverse correlation was found only between body mass index and serum middle molecular weight adiponectin level. After adjustment for confounding variables, the factor found to be most closely associated with endometrial cancer was a lower serum level of middle molecular weight adiponectin (adjusted odds ratio 4.89, 95 % confidence interval value 1.25-19.11, P = 0.022).

Low serum level of middle molecular weight adiponectin was the only independent risk factor for endometrial cancer suggesting that the application of adiponectin might prevent or decrease the risk for endometrial cancer.

Does transradial arterial chemoembolization reduce complications and costs in patients with hepatocellular carcinoma?

To improve patient comfort and reduce complications, clinical benefit of a transradial approach for transcatheter arterial chemoembolization (TACE) was evaluated in patients with hepatocellular carcinoma (HCC). A total of 284 patients with HCC for TACE was divided into transradial approach group (n = 126) and transfemoral approach group (n = 158). These two groups of cases were retrospectively compared with regard to complications, the procedural time, X-ray exposure time, length of hospitalization, and hospital costs. There were lower incidence rates of complications including abdominal distension (42.85% vs. 87.97%, P> 0.001), vomiting (53.17% vs. 77.22%, P < 0.001), lumbago (1.59% vs. 97.46%, P < 0.001), and dysuria (0% vs. 62.03%, P < 0.001) in the transradial group as compared with the transfemoral group. The time required for catheterization and total X-ray exposure time were less in the transradial group compared with the transfemoral group (Pall < 0.001). The hospital stay time and costs required for catheterization were less in the transradial group compared with the transfemoral group (P < 0.001 and P = 0.001, respectively). In addition, hepatic angiography and TACE were completed in 100% and 99.2% cases in transfemoral and transradial groups, respectively.

Transradial approach for TACE improves quality of life in patients with HCC by offering fewer complications and lower costs compared with transfemoral approach.

Is minimally invasive surgery safe and effective for urgent and emergent colectomy?

There are a limited number of studies describing the role of minimally invasive colectomy for urgent or emergent conditions of the large bowel. We hypothesize that laparoscopic colectomy in urgent and emergent setting can be performed safely in select settings. A cohort of patients treated at a single institution from 2001 to 2006 was identified from a prospective database. Patients who underwent open or minimally invasive surgery (MIS), including laparoscopic (LAP) or hand-assisted laparoscopic surgery (HALS) colectomy for urgent and emergent conditions were included. A total of 68 [open 32, MIS 36 [HALS 22, LAP 14)] patients underwent urgent or emergent colectomy on our colorectal service during the 5-year time period. Patients with toxic colitis were more often selected for MIS. Patients with colon perforation or large bowel obstruction were more often selected for open surgery. The MIS group had a lower body mass index (BMI), lower American Society of Anesthesiologists fitness grade and was more likely to have been immunosuppressed. There was no difference in patient morbidity between the open and MIS groups. The MIS group had a longer median operative time and fewer cases of prolonged hospitalization.

We conclude that minimally invasive colectomy by experienced surgeons appears to be safe and effective for appropriately selected patients with emergent and urgent conditions of the large bowel.

Does 1.5 Harmonic Imaging Sonography with microbubble contrast agent improve characterization of hepatocellular carcinoma?

To investigate the usefulness of 1.5 Harmonic Imaging Sonography with the use of the contrast agent Levovist for the diagnosis of hepatocellular carcinoma (HCC) and for the evaluation of therapeutic response. Phantom experiments were performed to compare the contrast effects of 2(nd) harmonic imaging and 1.5 Harmonic Imaging Sonography. 1.5 Harmonic Imaging Sonography was employed to examine 36 patients with HCC (42 nodules) before and after the treatment and to compare against the findings obtained using other diagnostic imaging modalities. In 1.5 Harmonic Imaging Sonography, the tumor vessels of HCCs were clearly identified during the early phase, and late-phase images clearly demonstrated the differences in contrast enhancement between the tumor and surrounding hepatic parenchyma. Blood flow within the tumor was detected in 36 nodules (85.7%) during the early phase and in all 42 nodules (100%) during the late phase using 1.5 Harmonic Imaging Sonography, in 38 nodules (90.5%) using contrast-enhanced CT, in 34 nodules (81.0%) using digital subtraction angiography (DSA), and in 42 nodules (100%) using US CO(2) angiography. Following transcatheter arterial embolization, 1.5 Harmonic Imaging Sonography detected blood flow and contrast enhancement within the tumors that were judged to contain viable tissue in 20 of 42 nodules (47.6%). However, 6 of these 10 cases were not judged in contrast-enhanced CT. 1.5 Harmonic Imaging Sonography was compared with the US CO(2) angiography findings as the gold standard, and the sensitivity and specificity of these images for discerning viable and nonviable HCC after transcatheter arterial embolization were 100% and 100%, respectively.

1.5 Harmonic Imaging Sonography permits the vascular structures of HCCs to be identified and blood flow within the tumor to be clearly demonstrated. Furthermore, 1.5 Harmonic Imaging Sonography is potentially useful for evaluating the therapeutic effects of transcatheter arterial embolization on HCC.

Are the material properties and matrix composition of equine flexor and extensor tendons determined by their functions?

Injury to the superficial digital flexor tendon (SDFT) is common in competition horses. The SDFT contributes to locomotory efficiency by storing energy; such tendons have low safety margins. Tendons which merely position the limb, including the opposing common digital extensor tendon (CDET), are rarely injured. The current failure of strategies to prevent or effectively treat injury to the SDFT indicates the importance of understanding how it differs from tendons which are not injury-prone. That the structural and material properties and matrix composition of the SDFT and CDET differ, reflecting their specific functional requirements in vivo. Forelimb tendons were harvested from 26 mature horses and loaded to failure prior to matrix composition analysis of specimens. The SDFT had a significantly higher cross-sectional area, structural stiffness, failure load and failure strain and a lower elastic modulus than the CDET (P<0.0001).

The SDFT has conflicting requirements for strength and elasticity; although as a whole it is a stiffer structure than the CDET, differences in the matrix molecular composition including water and total sulphated glycosaminoglycan contents allow it to remain more elastic as a material.

Do transcription enhancer factor-1-related factor-transgenic mice develop cardiac conduction defects associated with altered connexin phosphorylation?

Conduction system defects and slowed ventricular conduction are common in patients with systolic dysfunction and contribute to arrhythmias and sudden death. In animal models of heart failure, cardiac alpha1-adrenergic signaling is constitutively activated. Here, we report the effects of constitutive activation of alpha1-adrenergic signaling on connexin phosphorylation and cardiac conduction. Transgenic mice were generated with cardiac-specific overexpression of the transcription factor RTEF-1 (transcription enhancer factor-1-related factor), which mediates alpha1-adrenergic signaling in cardiac myocytes. Surface and intracardiac ECGs revealed prolongation of the PR, QRS, and AH intervals and the appearance of progressive atrial arrhythmias in RTEF-1 mice. Optical mapping using voltage-sensitive dye revealed slower conduction velocities across the atrial and ventricular myocardium. Intercellular dye transfer between RTEF-1 transgenic cardiac myocytes confirmed impaired conduction at the cellular level. Conduction defects were correlated with dephosphorylation of connexin40 and connexin43 and upregulation of protein phosphatase 1beta (PP1beta). Overexpression of PP1beta in HeLa cells dephosphorylated cardiac connexin. Confocal microscopy revealed increased levels of dephosphorylated connexin43 at the cardiac gap junctions in RTEF-1 mice, suggesting that defective conduction is a result of impaired gap-junction conductance rather than assembly.

Constitutive activation of alpha1-adrenergic signaling through the RTEF-1 transcription factor results in chronic elevation of PP1beta expression and connexin dephosphorylation. This mechanism may underlie some defects in cardiac conduction.

Is total pulmonary vein diameter a strong predictor of atrial fibrillation after coronary artery bypass graft surgery?

Recent studies have shown that the pulmonary veins are important in atrial fibrillation (AF). This study evaluated the relationship between total pulmonary vein diameter and postoperative AF in on-pump coronary artery bypass graft (CABG) patients. Our study enrolled 149 patients undergoing on-pump CABG. The primary endpoint was defined as postoperative new-onset in-hospital AF. All patients underwent preoperative non-contrast tomography to measure pulmonary vein diameter. The patients who developed AF had significantly greater total pulmonary vein diameters than those who remained in sinus rhythm. Logistic multivariate regression analysis revealed that only total pulmonary vein diameter was an independent predictor of the development of new-onset AF.

To our knowledge, this is the first report of an association between total pulmonary vein diameter and the development postoperative AF. The identification of high-risk patients using pulmonary vein diameters should facilitate preventive measures.

Do cardiomyocyte intracellular calcium and cardiac dysfunction after burn trauma?

To examine the effects of pharmacologic agents designed to limit burn-mediated calcium overload on cardiomyocyte [Ca2+] and cardiac contractile function. Experimental, comparative study. Cellular biology and physiology laboratory. Adult Sprague Dawley rats. Rats were given third-degree burn injury over 40% of the total body surface area, were fluid resuscitated, and then were divided randomly to receive one of five treatments: vehicle (normal saline); amiloride (50 mg/kg) to inhibit H+-Na+ exchange and subsequent Na+-Ca2+ exchange; dantrolene (10 mg/kg, 30 mins, 6 and 22 hrs postburn) to inhibit sarcoplasmic reticulum Ca2+ release; diltiazem (10 mg/kg given over first 6 hrs postburn); or amlodipine (0.07 mg/kg, 24 hrs preburn and 30 mins postburn) to block calcium slow channels. Appropriate controls (sham burns given the appropriate pharmacologic agent) were included in each group. Twenty-four hrs postburn, left ventricular function (Langendorff), cardiomyocyte [Ca2+]i and [Na+]i measured by fura-2-AM or sodium-binding benzofurzan isophthalate loading of cardiomyocytes, and myocyte secretion of tumor necrosis factor-alpha (enzyme-linked immunosorbent assay) were assessed in shams and burns from each experimental group. This time point was selected based on our previous work confirming maximal ventricular contractile defects and maximal cytokine secretion 24 hrs postburn. Burn trauma increased myocyte [Ca2+]i and [Na+]i, promoted tumor necrosis factor-alpha secretion by cardiomyocytes, and impaired left ventricular function. All pharmacologic agents reduced the burn-mediated Ca2+/Na+ accumulation in cardiomyocytes and ablated burn-mediated tumor necrosis factor-alpha secretion by myocytes; in contrast, dantrolene and amiloride provided significantly greater cardioprotection than pharmacologic agents that specifically targeted Ca2+ slow channels (diltiazem and amlodipine).

Our data suggest that the calcium antagonists used in this study provide cardioprotection by modulating several aspects of the overall inflammatory cascade rather than solely limiting cardiomyocyte accumulation of calcium.

ECG-gated 99mTc single-photon emission CT for assessment of right ventricular structure and function: is the information provided similar to echocardiography?

(99m)Tc single-photon emission CT (SPECT) and ECG-gated SPECT can visualize well the right ventricle (RV) in most patients, but their utility for assessment of the RV has not been formally evaluated. We examined whether (99m)Tc SPECT/ECG-gated SPECT provide similar information to transthoracic two-dimensional Doppler echocardiography (2D-ECHO) regarding RV cavity size, wall thickness, and systolic function. Retrospective analysis. A major university teaching hospital. A consecutive series of 194 patients with good quality stress SPECT and 2D-ECHO studies performed within 1 day of each other and no significant interim cardiac events. RV size and function were visually assessed by SPECT/ECG-gated SPECT and 2D-ECHO. RV wall thickness was visually assessed by SPECT and measured in mm in end-diastole by 2D-ECHO. Of 142 patients with normal RV cavity size by SPECT, 134 patients (94%) had normal RV cavity size by 2D-ECHO. However, of 52 patients with RV dilation by SPECT, only 9 patients (17%) had RV dilation by 2D-ECHO. A perfusion abnormality in the right coronary artery territory was significantly associated with RV dilation by SPECT (p<0.005) and 2D-ECHO (p<0.05). Among 150 patients with ECG-gated SPECT, only 2 patients had abnormal RV systolic function, as compared with 18 patients by 2D-ECHO. RV wall thickness measurements by SPECT and 2D-ECHO did not correlate.

For normal interpretations regarding RV cavity size, wall thickness, and systolic function, there is good agreement between (99m)Tc stress SPECT/ECG-gated SPECT and 2D-ECHO. However, there is poor overall agreement between gated SPECT/ECG-gated SPECT and 2D-ECHO regarding the presence of RV dilation, hypertrophy, and systolic dysfunction.

Does a social model of hospice day care affect advanced cancer patients' use of other health and social services?

Hospice day care (HDC) services have developed but no trials evaluate their impact on the other health and social care services. The purpose of this study was to evaluate the effect of HDC on the use of health and social services in a prospective quasi-experimental study. The trial compared consecutive patients receiving HDC, with two control groups: a 'before' group and a 'standard care' group. All data was collected in face to face interviews at baseline and then at 6-8 weeks and 12-15 weeks. The health and social service use at baseline and follow-up interviews were examined by five categories (community, hospice, social care support, hospital, and therapist). The multivariate analysis of covariance (MANCOVA) was used to test service use differences between groups, adjusting for potential confounders. In total, 37, 50, and 76 patients were recruited to the day care, standard care and before groups. Patients in the HDC group used significantly more social care support (11.5 +/- 18.9 versus 3.2 +/- 10.0, P = 0.015) and therapists (0.9 +/- 1.7 versus 0.2 +/- 0.4, P = 0.009) than the standard care at the baseline. The therapist service use from the baseline to the first follow-up reduced (mean change +/- SD, -0.3 +/- 0.6; 95%CI, -0.7 to 0.0) in the HDC group and increased in the standard care group (mean change +/- SD, 0.1 +/- 0.5; 95%CI, -0.1 to 0.3), the difference was significant (P = 0.003). No other changes in service use were significant in other study periods.

HDC appears to supplement existing services with little effect on the other community and hospital services.

Does transregulation of adenylyl-cyclase-coupled inhibitory receptors in heart failure enhance anti-adrenergic effects on adult rat cardiomyocytes?

In congestive heart failure (CHF), a desensitisation of stimulatory beta-receptors and of adenylyl cyclase in the heart is associated with an increase in inhibitory Gi proteins. To investigate whether the regulation of the Gi-mediated inhibitory side of the adenylyl cyclase system may be of functional importance in the failing myocardium, the contractile response of isolated adult cardiomyocytes to stimulation of inhibitory muscarinic M2 and A1 adenosine receptors was analysed. CHF was induced in rats by banding of the ascending aorta and was verified by doubling of lung wet weight. After four weeks, contraction amplitude (delta L) and the velocity (dL/dtmax) of isolated ventricular cardiomyocytes during electrical field stimulation in the presence of 1 mM Ca2+ were measured using video micrometry. Contractile responses of failing cardiomyocytes to 5 mM Ca2+ were unchanged. The response to increasing concentrations of the beta-adrenergic agonist, isoproterenol (0.1-30 nM), and to forskolin (0.1 nM-1 microM) were significantly blunted. When A1 receptors were activated with N6-(R-phenyl-isopropyl)-adenosine (PIA; 0.01-1 microM) in the presence of 3 nM isoproterenol, contractility was unchanged in cells compared with those from sham-operated rats, but delta L was reduced by up to 23% and dL/dtmax by 35% in failing cardiomyocytes (P < 0.01), demonstrating an enhanced inhibitory effect of A1 receptors. The response to the M2 receptor agonist, carbachol (0.01-3 microM), was augmented to a comparable extent (delta L, -22%, dL/dtmax, -39%; P < 0.01).

In CHF, the inotropic responses to beta-receptor-stimulation and to direct stimulation of adenylyl cyclase, but not to Ca2+, are diminished due to desensitisation of the stimulatory side of the adenylyl cyclase signal transduction system. In parallel, the responses to inhibitory receptors are augmented, leading to a pronounced Gi-mediated negative inotropic effect on failing heart muscle cells. Those anti-adrenergic effects could contribute to the contractile dysfunction of the failing heart. Reversal of the sensitisation to inhibitory stimuli might be one of the desirable mechanisms of medical therapy in CHF.

Nonsurgical management of high-risk lesions diagnosed at core needle biopsy: can malignancy be ruled out safely with breast MRI?

The purpose of this study was to investigate whether breast MRI can be used to rule out malignancy in patients with high-risk lesions diagnosed at imaging-guided core needle biopsy. The subjects were women consecutively registered between October 2004 and April 2010 who had high-risk lesions diagnosed at mammographically or sonographically guided core needle biopsy and subsequently underwent MRI and surgical excision. MR images were reviewed by two experienced breast radiologists. Lesions assessed as BI-RADS category 1-3 were considered negative for malignancy, and BI-RADS 4 and 5 lesions were considered malignant. Histologic findings at surgical excision were the reference standard. The sensitivity, specificity, and positive and negative predictive values of MRI in the detection of associated malignancy were calculated for the entire set of lesions and for each histologic subtype. The final sample consisted of 169 high-risk lesions in 166 patients. At MRI analysis, 116 (68.6%) lesions were considered negative for malignancy, and the other 53 (31.4%) malignant. At surgical excision, 22 malignant lesions were found. The overall sensitivity, specificity, and positive and negative predictive values of MRI were 72.7% (16/22), 74.8% (110/147), 30.2% (16/53), and 94.8% (110/116). The negative predictive values for papilloma, radial scar, lobular neoplasia, and atypical ductal hyperplasia were 97.4% (38/39), 97.6% (41/42), 88.0% (22/25), and 90.0% (9/10).

Patients with high-risk lesions associated with the lowest likelihood of malignancy (papilloma and radial scar) and without suspicious MRI findings can safely undergo follow-up instead of surgery. Because of the low negative predictive value, however, MRI is not helpful in cases of lobular neoplasia and atypical ductal hyperplasia, and all these lesions should be excised.

Does maternal nutrition induce gene expression changes in fetal muscle and adipose tissues in sheep?

Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. Here, we evaluated the impact of different maternal isoenergetic diets, alfalfa haylage (HY; fiber), corn (CN; starch), and dried corn distillers grains (DG; fiber plus protein plus fat), on the transcriptome of fetal muscle and adipose tissues in sheep. Prepartum diets were associated with notable gene expression changes in fetal tissues. In longissimus dorsi muscle, a total of 224 and 823 genes showed differential expression (FDR ≤0.05) in fetuses derived from DG vs. CN and HY vs. CN maternal diets, respectively. Several of these significant genes affected myogenesis and muscle differentiation. In subcutaneous and perirenal adipose tissues, 745 and 208 genes were differentially expressed (FDR ≤0.05), respectively, between CN and DG diets. Many of these genes are involved in adipogenesis, lipogenesis, and adipose tissue development. Pathway analysis revealed that several GO terms and KEGG pathways were enriched (FDR ≤0.05) with differentially expressed genes associated with tissue and organ development, chromatin biology, and different metabolic processes.

These findings provide evidence that maternal nutrition during pregnancy can alter the programming of fetal muscle and fat tissues in sheep. The ramifications of the observed gene expression changes, in terms of postnatal growth, body composition, and meat quality of the offspring, warrant future investigation.

Does lPS-induced NF-kappa B activation require Ca2+ as a mediator in isolated pancreatic acinar cells of rat?

To investigate the effect of Ca(2+) on lipopolysaccharide (LPS)-induced NF-kappa B activation in pancreatic acinar cells and the role of NF-kappa B in LPS-induced acinar cell injury. Male rat pancreatic acinar cells were isolated by collagenase digestion, then exposed to varying concentrations of LPS (from 1 to 20 mg/L) in the presence or absence of EGTA. At various time points (30 minutes, 1 hour, 2 hours, 4 hours and 10 hours) after treatment with the agents, cell viability was determined by MTT. Nuclear translocation of NF-kappa B's subunit p65 was visualized by immunofluorescence staining and nuclei protein was extracted to perform EMSA which was used to assay the activity of NF-kappa B binding to the DNA sequence containing the recognition site of NF-kappa B. LPS induced cell damage in a time- and concentration-dependent manner while EGTA attenuated LPS-induced cell damage (P < 0.05). NF-kappa B p65 immunofluorescence staining had increased intensity in the cytoplasm and indicated that nuclear translocation occurred within 30 minutes and its zenith was reached at 1 hour after LPS (10 mg/L) treatment. Testing of NF-kappa B DNA binding activity showed the same alteration phase as p65 immunofluorescence staining. NF-kappa B activation preceded the pathological alteration of pancreatic acinar cells. The Ca(2+) chelator EGTA inhibited LPS-induced NF-kappa B activation.

NF-kappa B activation is an important early event in LPS-induced injury to pancreatic acinar cells. Ca(2+) is an important mediator in the process of LPS-induced NF-kappa B activation.

Is clinically recognizable error rate after the transfer of comprehensive chromosomal screened euploid embryos low?

To determine the clinically recognizable error rate with the use of quantitative polymerase chain reaction (qPCR)-based comprehensive chromosomal screening (CCS). Retrospective study. Multiple fertility centers. All patients receiving euploid designated embryos. Trophectoderm biopsy for CCS. Evaluation of the pregnancy outcomes following the transfer of qPCR-designated euploid embryos. Calculation of the clinically recognizable error rate. A total of 3,168 transfers led to 2,354 pregnancies (74.3%). Of 4,794 CCS euploid embryos transferred, 2,976 gestational sacs developed, reflecting a clinical implantation rate of 62.1%. In the cases where a miscarriage occurred and products of conception were available for analysis, ten were ultimately found to be aneuploid. Seven were identified in the products of conception following clinical losses and three in ongoing pregnancies. The clinically recognizable error rate per embryo designated as euploid was 0.21% (95% confidence interval [CI] 0.10-0.37). The clinically recognizable error rate per transfer was 0.32% (95% CI 0.16-0.56). The clinically recognizable error rate per ongoing pregnancy was 0.13% (95% CI 0.03-0.37). Three products of conception from aneuploid losses were available to the molecular laboratory for detailed examination, and all of them demonstrated fetal mosaicism.

The clinically recognizable error rate with qPCR-based CCS is real but quite low. Although evaluated in only a limited number of specimens, mosaicism appears to play a prominent role in misdiagnoses. Mosaic errors present a genuine limit to the effectiveness of aneuploidy screening, because they are not attributable to technical issues in the embryology or analytic laboratories.

Do electrophysiologic and clinical data support the use of dorsal root entry zone myelotomy in syringosubarachnoid shunting for syringomyelia?

The objectives of this study were to correlate preoperative changes in SEPs with clinical sensory dysfunction and to establish their importance in planning the microsurgical approach, either by DM myelotomy or by DREZ myelotomy, for patients with syringomyelia. In addition to conducting clinical sensory examination, we evaluated the N13 potential after median nerve stimulation and CPs after tibial nerve stimulation intraoperatively before performing myelotomy on patients with syringomyelia (N = 14). Eleven patients with intact DS presented with unilateral PTD, and 9 had distressing unilateral dermatomal pain. Deep sensibility was affected in 3 patients (bilaterally in 1 patient) without PTD. Patients with PTD were likely to have spontaneous pain (P = .005). A significant correlation between preoperative PTD and the absence of the N13 potential was demonstrated on the right (P = .015) and left (P = .004) sides. In patients with PTD, DREZ myelotomy on the symptomatic side is suggested as the treatment of choice, whereas DM myelotomy might be superior in patients without PTD.

Absence of pain or temperature sensation in patients with syringomyelia is usually accompanied by same-sided loss of the N13 potential, suggesting damage to the DH gray matter. Deep sensibility is typically normal, and DREZ myelotomy with preservation of DCs is proposed as the treatment of choice. Conducted potentials are usually distorted in patients with normal pain or temperature sensation and affected vibration and posture sensation, suggesting damage to DCs and making DM myelotomy the treatment of choice. Electrophysiologic and clinical data support the use of DREZ myelotomy in syringosubarachnoid shunting for syringomyelia in patients whose DCs have an intact function.

Are panoramic images reliable in planning sinus augmentation procedures?

The inherent deformation and two-dimensional nature of panoramic radiographs jeopardise their interpretation and quantitative measurements. This study aims to estimate the degree of underestimation of available mesio-distal bone in the premolar area (comparing panoramic radiographs with multi-slice/cone-beam computer tomography [CT]) to determine the prevalence, width, length and position of the bony canal [artery]in the lateral sinus wall and to explore the prevalence, width and length of another (newly detected) bony canal at the palatal aspect of the upper canine. The distance between the distal side of the canine/first premolar and the mesial side of the first molar or the anterior wall of the maxillary sinus was measured on panoramic radiographs and corresponding multi-slice/cone-beam CT images (65 patients). Measurements were made at apical, mid-radicular and crestal regions, parallel to the occlusal plane. The presence and dimensions of the two above-mentioned intra-osseous canals were verified on multi-slice CT scans (144 patients) using reformatted cross-sectional images and/or axial slices. For all 65 patients, panoramic radiographs underscored the mesio-distal distance of available bone in the upper premolar region (mean 2.9 mm, range 0.1-7.5 mm). An intra-osseous canal in the lateral maxillary sinus wall was clearly visible in 49.5% of the cases (mean diameter 1.4 mm). In the canine region, a bony canal was obvious in 32.9% of the cases, with a mean diameter of 1.23 mm. For both canals, there was no correlation between diameter and patient's age.

Based on the present data, cone-beam CT imaging can be recommended for visualising anatomical structures during planning of sinus augmentation procedures.

Liver resection without total vascular exclusion: hazardous or beneficial?

To evaluate retrospectively the safety and radicality of liver resection performed without total vascular exclusion (TVE). TVE is recommended for safe liver surgery, at least in the case of resection of the paracaval portion of the liver. However, it has some drawbacks because of its invasiveness. The authors retrospectively evaluated 329 of 471 consecutive patients who underwent liver resection from October 1994 to October 1999. All of these patients had tumors involving segments 1, 7, or 8 or the cranial portion of segment 4, or underwent major hepatectomies that required exposure of the inferior vena cava (IVC), the main trunks of the hepatic veins, or both. Sixty-four patients underwent resection that included segment 1, with or without the reconstruction of the IVC, the hepatic vein, or both. Three hundred twenty-four of 329 procedures were done under intermittent warm ischemia; no clamping methods were used in 6. TVE was never needed. There were no postoperative 30-day deaths. The complication rate was 25.5%, and only 2.1% had major complications. Only 13 (3.9%) patients required whole blood transfusion. Part of the wall of the IVC was resected in six patients, and the hepatic veins were reconstructed in four. Surgical clearance was achieved in all patients undergoing surgery for a tumor.

These results show that liver surgery performed without TVE is safe and effective even in aggressive procedures for liver tumors involving the cavohepatic junction. Therefore, TVE should be further restricted to exceptional patients.

Are chemokine CCL2 and its receptor CCR2 increased in the hippocampus following pilocarpine-induced status epilepticus?

Neuroinflammation occurs after seizures and is implicated in epileptogenesis. CCR2 is a chemokine receptor for CCL2 and their interaction mediates monocyte infiltration in the neuroinflammatory cascade triggered in different brain pathologies. In this work CCR2 and CCL2 expression were examined following status epilepticus (SE) induced by pilocarpine injection. SE was induced by pilocarpine injection. Control rats were injected with saline instead of pilocarpine. Five days after SE, CCR2 staining in neurons and glial cells was examined using imunohistochemical analyses. The number of CCR2 positive cells was determined using stereology probes in the hippocampus. CCL2 expression in the hippocampus was examined by molecular assay. Increased CCR2 was observed in the hippocampus after SE. Seizures also resulted in alterations to the cell types expressing CCR2. Increased numbers of neurons that expressed CCR2 was observed following SE. Microglial cells were more closely apposed to the CCR2-labeled cells in SE rats. In addition, rats that experienced SE exhibited CCR2-labeling in populations of hypertrophied astrocytes, especially in CA1 and dentate gyrus. These CCR2+ astroctytes were not observed in control rats. Examination of CCL2 expression showed that it was elevated in the hippocampus following SE.

The data show that CCR2 and CCL2 are up-regulated in the hippocampus after pilocarpine-induced SE. Seizures also result in changes to CCR2 receptor expression in neurons and astrocytes. These changes might be involved in detrimental neuroplasticity and neuroinflammatory changes that occur following seizures.

Do dithiolane analogs of lignans inhibit interferon-gamma and lipopolysaccharide-induced nitric oxide production in macrophages?

To investigate the effect of a group of novel synthetic dithiolane analogs of lignans and a well characterized platelet-activating factor (PAF) receptor antagonist, L659,989 on PAF-receptor binding, IFN-gamma- and lipopolysaccharide (LPS)-induced NO production, and steady-state inducible nitric-oxide synthase (iNOS) mRNA expression. PAF-receptor binding study was performed by displacement of 3H-PAF from rabbit platelet membrane; NO production was quantitated by measuring the NO oxidation product, nitrite, in conditioned culture medium; expression of iNOS mRNA was assessed by Northern blot analysis. The dithiolane analogs inhibited the production of NO, decreased iNOS mRNA expression and antagonized PAF-receptor binding. L659,989 had no effect on NO production and iNOS mRNA expression. Among the compounds tested, there was no simple correlation between their PAF-receptor antagonistic and iNOS inhibitory activities.

The dithiolane analogs are a new synthetic chemical class of iNOS expression regulators with dual biologic functions: inhibiting iNOS induction and blocking PAF-receptor.

Are global DNA methylation patterns in Barrett 's esophagus , dysplastic Barrett 's , and esophageal adenocarcinoma associated with BMI , gender , and tobacco use?

The risk of developing Barrett's esophagus (BE) and/or esophageal adenocarcinoma (EAC) is associated with specific demographic and behavioral factors, including gender, obesity/elevated body mass index (BMI), and tobacco use. Alterations in DNA methylation, an epigenetic modification that can affect gene expression and that can be influenced by environmental factors, is frequently present in both BE and EAC and is believed to play a role in the formation of BE and its progression to EAC. It is currently unknown whether obesity or tobacco smoking influences the risk of developing BE/EAC via the induction of alterations in DNA methylation. To investigate this possibility, we assessed the genome-wide methylation status of 81 esophageal tissues, including BE, dysplastic BE, and EAC epithelia using HumanMethylation450 BeadChips (Illumina). We found numerous differentially methylated loci in the esophagus tissues when comparing males to females, obese to lean individuals, and smokers to nonsmokers. Differences in DNA methylation between these groups were seen in a variety of functional genomic regions and both within and outside of CpG islands. Several cancer-related pathways were found to have differentially methylated genes between these comparison groups.

Our findings suggest obesity and tobacco smoking may influence DNA methylation in the esophagus and raise the possibility that these risk factors affect the development of BE, dysplastic BE, and EAC through influencing the epigenetic status of specific loci that have a biologically plausible role in cancer formation.

Does administration of heparanase-III improve the survival and angiogenesis of rat skin autografts?

Heparanase, a glycohydrolase enzyme, cleaves heparan sulfate in the tissue matrix. Heparan sulfate degradation causes the release of angiogenic and growth factors, leading to angiogenesis. The aim of this paper was to evaluate the angiogenic effect of heparinase-III administration on skin autograft healing in rat. Four groups of 14 adult male Charles River rats were enrolled. Full thickness skin autografts (15 mm in diameter) were made on the interscapular region of each rat. After 24 hours, 0.1 cc of heparanase, at the three concentrations of 0.1, 0.2, and 0.4 units, were injected intradermally into the grafts of each of the three case groups. The control group received an equal volume of the vehicle (buffered phosphate solution). After 5 days, biopsy specimens from skin grafts of 5 randomly selected rats of each group were submitted for histological studies. The concentration of vessels (with 5-50 mm in diameter) in the grafts of the groups receiving 0.2 and 0.4 units of heparanase-III was significantly more than that of the control group (100.43+/-11.24 and 95.85+/-12.44 vs 71.42+/-5.22 vessels/mm(2), P<0.05). The graft survival time of the group that received 0.2 U heparanase-III was significantly longer than that of the control group (15.43+/-0.72 vs 13.23+/-0.69 days; P<0.05).

Heparanase-III administration improves the healing of rat skin autografts through induction of angiogenesis.