title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Hyperosmotic stress contributes to mouse colonic inflammation through the methylation of protein phosphatase 2A. | There are several reports suggesting hyperosmotic contents in the feces of patients suffering from inflammatory bowel disease (IBD). Previous works have documented that hyperosmolarity can cause inflammation attributable to methylation of the catalytic subunit of protein phosphatase 2A (PP2A) and subsequent NF-kappaB activation resulting in cytokine secretion. In this study, we demonstrate that dextran sulfate sodium (DSS) induces colitis due to hyperosmolarity and subsequent PP2A activation. Mice were randomized and fed with increased concentrations of DSS (0 mOsm, 175 mOsm, 300 mOsm, and 627 mOsm) for a duration of 3 wk or with hyperosmotic concentrations of DSS (627 mOsm) or mannitol (450 mOsm) for a duration of 12 wk. Long-term oral administration of hyposmotic DSS or mannitol had no demonstrable effect. Hyperosmotic DSS or mannitol produced a significant increase in colonic inflammation, as well as an increase in the weight of sacral lymph nodes and in serum amyloid A protein levels. Similar results were obtained through the ingestion of comparable osmolarities of mannitol. Hyperosmolarity induces the methylation of PP2A, nuclear p65 NF-kappaB activation. and cytokine secretion. The rectal instillation of okadaic acid, a well-known PP2A inhibitor, reverses the IBD. Short inhibiting RNAs (siRNAs) targeted toward PP2Ac reverse the effect of hyperosmotic DSS. The present study strongly suggests that DSS-induced chronic colitis is a consequence of the methylation of PP2Ac induced by hyperosmolarity. | 18,755,808 |
Effects of quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone on the survival of human neuronal and immune cells in vitro. | Because there are reports on cytotoxic and cytoprotective effects of antipsychotics, the aim of the present study was to evaluate the impacts of different concentrations (1.6-50 microg/mL) of atypical antipsychotics on the survival of human neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and on energy metabolism (ATP level after the incubation with antipsychotics in the concentration of 25 microg/mL). Statistical analysis showed that incubation for 24 h with the antipsychotics quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone led to a significantly enhanced cell survival in both cell lines in the lower concentrations. Higher concentrations exerted in part cytotoxic effects with the exception of quetiapine, but therapeutically relevant concentrations of the drugs were not cytotoxic in our experiments. Measurement of ATP contents in the neuronal cell line showed significantly increased levels after a 24-h treatment with 25 microg/mL risperidone and 9-hydroxyrisperidone. The other substances produced no effects. Our results show that the antipsychotic substances under investigation exert concentration-dependent effects on cell survival in both cell lines examined. | 18,755,815 |
Association of killer cell immunoglobulin-like receptor genotypes with vascular arterial events and anticardiolipin antibodies in patients with lupus. | To determine whether killer cell immunologlobulin-like receptor (KIR) genotypes are associated with vasculitis, vascular arterial events or anticardiolipin (aCL) antibodies in patients with lupus. A total of 304 patients followed prospectively at the University of Toronto Lupus Clinic were assessed for the occurrence of vasculitis and vascular arterial events. Molecular HLA-C and KIR (presence or absence of KIR2DL1, 2DL2, 2DL3, 2DS1 and 2DS2) genotyping were performed. Chi-square and logistic regression were used to analyse association between KIR genes and vascular arterial events and aCL antibodies. In patients with vascular arterial events, there was a significant increase in KIR2DS2 (60% vs 45%, P = 0.02) and in KIR2DL2 (62% vs 47%, P = 0.01) compared with patients without events. There was no increase in activating KIR genotypes in patients with vasculitis. In patients with aCL antibodies, significant increases were seen in KIR2DS2 (54% vs 41%, P = 0.03) and KIR2DL2 (58% vs 41%, P = 0.003), but KIR2DL3 was decreased (87% vs 95%, P = 0.03). Logistic regression confirmed independent association of KIR2DS2 with vascular arterial events. We found an increase in KIR2DS2 in lupus patients with vascular arterial events, but not in patients with vasculitis. | 18,755,860 |
A proteomic study of peripheral blood mononuclear cells in systemic lupus erythematosus. | Our objective was to analyze the changes in the protein expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE). Peripheral blood was obtained from patients with SLE and healthy controls. 2-D gel electrophoresis was performed, and gels were silver-stained. Differentially expressed protein spots were detected, some of which were identified by MALDI-TOF spectrometry. Match rates of 71% +/- 4% and 72% +/- 4% were gotten for control and patient gels, respectively. 791 +/- 17 spots were detected for control gels and 781 +/- 17 for patient gels. Eleven protein spots were up-regulated, and 9 protein spots were down-regulated in patients with SLE. Five differentially expressed proteins were identified as immunoglobulin J chain, apolipoprotein A-IV precursor, calprotectin L1H and zinc finger protein subfamily 1A (all up-regulated) and glutathione S-transferase (down-regulated), some of which had previously been shown to play a potential role in the pathogenesis of SLE. We conclude there are significant changes in the 2-D maps of PBMCs in patients with SLE and applying this proteomic approach may be a useful way to gain novel insights into SLE. | 18,755,861 |
Cross-regulatory protein-protein interactions between Hox and Pax transcription factors. | Homeotic Hox selector genes encode highly conserved transcriptional regulators involved in the differentiation of multicellular organisms. Ectopic expression of the Antennapedia (ANTP) homeodomain protein in Drosophila imaginal discs induces distinct phenotypes, including an antenna-to-leg transformation and eye reduction. We have proposed that the eye loss phenotype is a consequence of a negative posttranslational control mechanism because of direct protein-protein interactions between ANTP and Eyeless (EY). In the present work, we analyzed the effect of various ANTP homeodomain mutations for their interaction with EY and for head development. Contrasting with the eye loss phenotype, we provide evidence that the antenna-to-leg transformation involves ANTP DNA-binding activity. In a complementary genetic screen performed in yeast, we isolated mutations located in the N terminus of the ANTP homeodomain that inhibit direct interactions with EY without abolishing DNA binding in vitro and in vivo. In a bimolecular fluorescence complementation assay, we detected the ANTP-EY interaction in vivo, these interactions occurring through the paired domain and/or the homeodomain of EY. These results demonstrate that the homeodomain supports multiple molecular regulatory functions in addition to protein-DNA and protein-RNA interactions; it is also involved in protein-protein interactions. | 18,755,899 |
Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations. | Depression and anxiety are significant comorbid and potentially modifiable conditions in chronic obstructive pulmonary disease (COPD), but their effects on exacerbations are not clear. To investigate the independent effect of depression and anxiety on the risk of COPD exacerbations and hospitalizations. A multicenter prospective cohort study in 491 patients with stable COPD in China. Multivariate Poisson and linear regression analyses were used, respectively, to estimate adjusted incidence rate ratios (IRRs) and adjusted effects on duration of events. Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS) at baseline. Other measurements included sociodemographic, clinical, psychosocial, and treatment characteristics. Patients were then monitored monthly for 12 months to document the occurrence and characteristics of COPD exacerbations and hospitalizations. Exacerbation was determined using both symptom-based (worsening of > or =1 key symptom) and event-based definitions (> or =1 symptom worsening plus > or =1 change in regular medications). A total of 876 symptom-based and 450 event-based exacerbations were recorded, among which 183 led to hospitalization. Probable depression (HADS depression score > or = 11) was associated with an increased risk of symptom-based exacerbations (adjusted IRR, 1.51; 95% confidence interval [CI], 1.01-2.24), event-based exacerbations (adjusted IRR, 1.56; 95% CI, 1.02-2.40), and hospitalization (adjusted IRR, 1.72; 95% CI, 1.04-2.85) compared with nondepression (score < or = 7). The duration of event-based exacerbations was 1.92 (1.04-3.54) times longer for patients with probable anxiety (HADS anxiety score > or = 11) than those with no anxiety (score < or = 7). This study suggests a possible causal effect of depression on COPD exacerbations and hospitalizations. Further studies are warranted to confirm this finding and to test the effectiveness of antidepressants and psychotherapies on reducing exacerbations and improving health resource utilizations. | 18,755,925 |
Natural selection on a major armor gene in threespine stickleback. | Experimental estimates of the effects of selection on genes determining adaptive traits add to our understanding of the mechanisms of evolution. We measured selection on genotypes of the Ectodysplasin locus, which underlie differences in lateral plates in threespine stickleback fish. A derived allele (low) causing reduced plate number has been fixed repeatedly after marine stickleback colonized freshwater from the sea, where the ancestral allele (complete) predominates. We transplanted marine sticklebacks carrying both alleles to freshwater ponds and tracked genotype frequencies over a generation. The low allele increased in frequency once lateral plates developed, most likely via a growth advantage. Opposing selection at the larval stage and changing dominance for fitness throughout life suggest either that the gene affects additional traits undergoing selection or that linked loci also are affecting fitness. | 18,755,942 |
Cavity optomechanics: back-action at the mesoscale. | The coupling of optical and mechanical degrees of freedom is the underlying principle of many techniques to measure mechanical displacement, from macroscale gravitational wave detectors to microscale cantilevers used in scanning probe microscopy. Recent experiments have reached a regime where the back-action of photons caused by radiation pressure can influence the optomechanical dynamics, giving rise to a host of long-anticipated phenomena. Here we review these developments and discuss the opportunities for innovative technology as well as for fundamental science. | 18,755,966 |
Polarized gamma-ray emission from the crab. | Pulsar systems accelerate particles to immense energies. The detailed functioning of these engines is still poorly understood, but polarization measurements of high-energy radiation may allow us to locate where the particles are accelerated. We have detected polarized gamma rays from the vicinity of the Crab pulsar using data from the spectrometer on the International Gamma-Ray Astrophysics Laboratory satellite. Our results show polarization with an electric vector aligned with the spin axis of the neutron star, demonstrating that a substantial fraction of the high-energy electrons responsible for the polarized photons are produced in a highly ordered structure close to the pulsar. | 18,755,970 |
The biologic properties of leukemias arising from BCR/ABL-mediated transformation vary as a function of developmental origin and activity of the p19ARF gene. | Recent reports have shown that upon expression of appropriate oncogenes, both stem cells and more differentiated progenitor populations can serve as leukemia-initiating cells. These studies suggest that oncogenic mutations subvert normal development and induce reacquisition of stem-like features. However, no study has described how specific mutations influence the ability of differentiating cell subsets to serve as leukemia-initiating cells and if varying such cellular origins confers a functional difference. We have examined the role of the tumor suppressor gene p19(ARF) in a murine model of acute lymphoblastic leukemia and found that loss of p19(ARF) changes the spectrum of cells capable of tumor initiation. With intact p19(ARF), only hematopoietic stem cells (HSCs) can be directly transformed by BCR/ABL expression. In a p19(ARF)-null genetic background expression of the BCR/ABL fusion protein renders functionally defined HSCs, common lymphoid progenitors (CLP), and precursor B-lymphocytes competent to generate leukemia stem cells. Furthermore, we show that leukemias arising from p19(ARF)-null HSC versus pro-B cells differ biologically, including relative response to drug insult. Our observations elucidate a unique mechanism by which heterogeneity arises in tumor populations harboring identical genetic lesions and show that activity of p19(ARF) profoundly influences the nature of tumor-initiating cells during BCR/ABL-mediated leukemogenesis. | 18,755,985 |
Use of clinical decision support to increase influenza vaccination: multi-year evolution of the system. | Despite recognition that clinical decision support (CDS) can improve patient care, there has been poor penetration of this technology into healthcare settings. We used CDS to increase inpatient influenza vaccination during implementation of an electronic medical record, in which pharmacy and nursing transactions increasingly became electronic. Over three influenza seasons we evaluated standing orders, provider reminders, and pre-selected physician orders. A pre-intervention cross-sectional survey showed that most patients (95%) met criteria for vaccination. During our intervention, physicians were increasingly likely to accept pre-selected vaccination orders, Year 1 (47%), Year 2 (77%), Year 3 (83%); however vaccine administration by nurses was suboptimal. As electronic medical record functionality improved, patient receipt of vaccine increased dramatically, Year 1 [0/36; 0%], Year 2 [8/66; 12%], Year 3 [286/805; 36%]. Successful use of clinical decision support to increase inpatient influenza vaccination only occurred after initiation of CPOE for all medications and integration of an electronic medication administration record. Also, since most patients met criteria for influenza vaccination, complicated logic to identify high-risk patients was unnecessary. | 18,756,001 |
Cardiovascular dynamics in healthy subjects with differing heart rate responses to tilt. | Orthostatic stress such as head-up tilt (HUT) elicits a wide range of heart rate (HR) and arterial pressure (AP) responses among healthy individuals. In this study, we evaluated cardiovascular dynamics in healthy subjects with different HR responses to HUT, but without autonomic dysfunction. We measured AP (brachial artery) and HR (ECG) during 5 min of 60 degrees HUT in 76 healthy normotensive individuals. We then chose individuals on the basis of the extremes of HR responses to HUT (high = DeltaHR > or = 20 beats/min, and low = DeltaHR < or = 10 beats/min; n = 15 per group). Peak HR during HUT was 87 +/- 10 beats/min in the high and 69 +/- 14 beats/min in the low group (P < 0.05). High HR responders had lower systolic pressure at baseline (121 +/- 9 vs. 129 +/- 11 mmHg, P < 0.05) and during HUT (120 +/- 10 vs. 131 +/- 13 mmHg, P < 0.05), and higher plasma norepinephrine (NE) response to HUT (DeltaNE: 156.9 +/- 17.8 vs. 89.0 +/- 17.2 pg/ml; P < 0.05). DeltaNE during HUT was also significantly correlated with DeltaHR when all 76 subjects were included in a regression analysis (r = 0.39; P < 0.001). Pulse pressure was lower during HUT in high HR responders compared with low HR responders (45 +/- 1 vs. 55 +/- 2 mmHg, P < 0.05). High HR responders also had larger fluctuations in systolic and pulse pressure during HUT (coefficient of variation = 10.7 +/- 0.7 vs. 5.7 +/- 0.3%; 7.9 +/- 0.5 vs. 4.1 +/- 0.4%, respectively, P < 0.05). Sex distribution was different between groups (high: 5 women, 10 men; low: 10 women, 5 men). Higher HR with lower AP during HUT is consistent with normal baroreflex mechanisms of integration. Although interindividual variability appears to be a fundamental part of cardiovascular regulation, the mechanisms of these differences and the sex discrepancy requires further investigation. | 18,756,006 |
Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer. | Evidence has emerged for a role of vitamin D in the development of breast cancer, and there is some suggestion that its antiproliferative effect is greater in hormone-receptor-positive cells. Few epidemiologic studies have considered the association between vitamin D and hormone-receptor-defined breast cancer, and the results are conflicting. Considering 759 cases and 1,135 controls from a case-control study (Ontario, Canada, 2003-2005), the authors examined the association between vitamin D intake at specific ages and combined estrogen-receptor- (ER) and progesterone-receptor- (PR) defined breast cancer. While increased intake of vitamin D (from the sun and diet) was most consistently associated with a significantly reduced risk of ER+/PR+ tumors (e.g., odds ratio = 0.76, 95% confidence interval: 0.59, 0.97 for use of cod liver oil during adolescence), comparable nonsignificant associations were found for receptor-negative (ER-/PR-) (odds ratio = 0.74, 95% confidence interval: 0.53, 1.04) and mixed (ER+/PR-) (odds ratio = 0.79, 95% confidence interval: 0.51, 1.22) tumors. This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor. Future studies with a larger number of receptor-negative and mixed tumors are required. | 18,756,015 |
Body weight and plasma levels of ghrelin and leptin during treatment with olanzapine. | Although enhanced appetite and weight gain are potential side effects of treatment with antipsychotic agents, particularly olanzapine and clozapine, the mechanisms underlying these side effects are poorly understood. Leptin and ghrelin were recently identified as hormones that play crucial roles in the regulation of energy balance and glucose metabolism. To elucidate relationships between weight change and plasma levels of ghrelin and leptin, we investigated the circulating ghrelin and leptin levels and body weight during olanzapine treatment. Twenty-four patients with schizophrenia were examined during 6-month administration of olanzapine. Ghrelin, leptin, weight and body mass index (BMI) were measured before and after 2, 4, 8, 12, 16, and 24 weeks of olanzapine treatment. The concentration of glucose and various lipid metabolic parameters were measured at baseline and at 24 weeks. Significant increases in weight, BMI and leptin were observed at week 24. On the other hand, the serum levels of ghrelin decreased significantly after olanzapine treatment. In addition, the level of ghrelin was negatively correlated with the leptin level, BMI and weight. The leptin level was positively correlated with both BMI and weight. Ghrelin is associated with metabolic changes, in combination with leptin, during olanzapine treatment. However, further large-scale and longitudinal studies are warranted to elucidate the metabolic changes involving ghrelin, leptin and insulin during treatment with antipsychotics. | 18,756,058 |
Benign schwannoma of the liver: a case report. | A primary benign schwannoma of the liver is extremely rare. Only nine cases have been reported in the medical literature worldwide and no case has been reported in Korea previously. A 36-yr-old woman was admitted to our hospital with vague epigastric pain. The ultrasound and computed tomography scan revealed a multi-septated cystic mass in the right lobe of the liver. The mass was resected; it was found to be a 5 x 4 x 2 cm mass filled with reddish yellow fluid. The histological examination confirmed the diagnosis of a benign schwannoma, proven by positive immunoreaction with the neurogenic marker S-100 protein and a negative response to CD34, CD117 and smooth muscle actin. This is the first report of a benign schwannoma of the liver parenchyma in a Korean patient. | 18,756,066 |
The rice genome structure as a trail from the past to beyond. | Rice is the first cultivated plant species to be completely sequenced. Cultivation, in general, is a major factor that contributes to selection pressure of a target species resulting in accelerated changes in genome structure from an original wild species. The genome sequence of cultivated rice can now be used as a standard for comparison with many other cultivated rice species, its wild relatives and other grass species. Several indices define the dynamic nature of genome structure and function. Genome dynamics in rice is described here based on transposon, retrotransposon and polyploidy. Comparative studies with other related grass species based on the principle of synteny are expected to generate invaluable information that will clarify the trail that led to the present cultivated rice as well as the trail that will lead to its further improvement. | 18,756,083 |
Heterologous expression and characterization of glycogen branching enzyme from Synechocystis sp. PCC6803. | A gene (sll0158) putatively encoding a glycogen branching enzyme (GBE, E.C. 2.4.1.18) was cloned from Synechocystis sp. PCC6803, and the recombinant protein expressed and characterized. The PCR-amplified putative GBE gene was ligated into a pET-21a plasmid vector harboring a T7 promoter, and the recombinant DNA transformed into a host cell, E. coli BL21(DE3). The IPTG-induced enzymes were then extracted and purified using Ni-NTA affinity chromatography. The putative GBE gene was found to be composed of 2,310 nucleotides and encoded 770 amino acids, corresponding to approx. 90.7 kDa, as confirmed by SDS-PAGE and MALDI-TOF-MS analyses. The optimal conditions for GBE activity were investigated by measuring the absorbance change in iodine affinity, and shown to be pH 8.0 and 30 degrees in a 50 mM glycine-NaOH buffer. The action pattern of the GBE on amylose, an alpha-(1,4)-linked linear glucan, was analyzed using high-performance anion-exchange chromatography (HPAEC) after isoamylolysis. As a result, the GBE displayed alpha-glucosyl transferring activity by cleaving the alpha-(1,4)-linkages and transferring the cleaved maltoglycosyl moiety to form new alpha-(1,6)- branch linkages. A time-course study of the GBE reaction was carried out with biosynthetic amylose (BSAM; Mp approximately = 8,000), and the changes in the branch-chain length distribution were evaluated. When increasing the reaction time up to 48 h, the weight- and number-average DP (DPw and DPn) decreased from 19.6 to 8.7 and from 17.6 to 7.8, respectively. The molecular size (Mp, peak Mw approximately = 2.45-2.75 x 10(5)) of the GBE-reacted product from BSAM reached the size of amylose (AM) in botanical starch, yet the product was highly soluble and stable in water, unlike AM molecules. Thus, GBE-generated products can provide new food and non-food applications, owing to their unique physical properties. | 18,756,098 |
Estimation of cardiovascular risk: a comparison between the Framingham and the SCORE model in people under 60 years of age. | The Framingham Heart Study risk model has been used in the majority of cardiovascular risk management guidelines. Recently, a new model based on the SCORE system has been proposed. We compared both risk models with regard to their ability to predict cardiovascular mortality in the Netherlands. Cohort study. In a Dutch cohort study of 39 719 persons, three properties of the risk models were investigated: discriminating ability (ranking persons in order of risks, expressed in area under the curve); calibrating ability (prediction of events compared with actual events expressed in goodness of fit); and the number of persons assigned to treatment according to the guideline. The discriminative ability of both models was similar: the area under the curve of Framingham was 0.86 and of SCORE 0.85. Calibration of both functions was inadequate. The goodness of fit of the SCORE model was 35 and of the Framingham model 64, whereas a goodness of fit less than 20 is considered acceptable. Using the Dutch guideline treatment threshold of 10% mortality risk, the SCORE risk function assigned 0.4% of the population to drug treatment where the Framingham function assigned 0.7%. The findings of this study show that both the SCORE and the Framingham model function have a good discriminative ability but are insufficient in predicting absolute risks. SCORE assigned fewer participants to treatment than Framingham. If a new risk model is implemented in treatment guidelines, comparison with the model in use and evaluation of calibrating features is needed. | 18,756,178 |
Quantum dots versus organic dyes as fluorescent labels. | Suitable labels are at the core of Luminescence and fluorescence imaging and sensing. One of the most exciting, yet also controversial, advances in label technology is the emerging development of quantum dots (QDs)--inorganic nanocrystals with unique optical and chemical properties but complicated surface chemistry--as in vitro and in vivo fluorophores. Here we compare and evaluate the differences in physicochemical properties of common fluorescent labels, focusing on traditional organic dyes and QDs. Our aim is to provide a better understanding of the advantages and limitations of both classes of chromophores, to facilitate label choice and to address future challenges in the rational design and manipulation of QD labels. | 18,756,197 |
Increases in weight and body size increase the odds for hypertension during 7 years of follow-up. | Changes in BMI and body size were compared to incident hypertension in 24,550 men and 10,111 women followed prospectively as part of the National Runners' Health Study to test whether long-term weight change affects hypertension risk. Incident hypertensions were reported by 2,143 men and 430 women during (mean +/- s.d.) 7.8 +/- 1.8 and 7.5 +/- 2.0 years of follow-up, respectively. Despite being active, men's and women's BMI increased 1.15 +/- 1.70 and 0.95 +/- 1.89 kg/m(2), respectively, and their waist circumferences increased 2.97 +/- 5.02 and 3.29 +/- 6.67 cm, respectively. Compared to those whose BMI declined, those who gained >or=2.4 kg/m(2) had an odds ratio (95% confidence interval) of 1.68 (1.45, 1.94) for becoming hypertensive if male and 1.42 (1.05, 1.92) if female. Men whose waist circumference increased >or=6 cm had an odds ratio of 1.22 (1.01, 1.47) for becoming hypertensive compared to those whose waists decreased. In both sexes, the odds for hypertension were significantly related to BMI at follow-up when adjusted for baseline BMI, but generally not to baseline BMI when adjusted for follow-up BMI. In the subset whose weights remained relatively unchanged during follow-up (+/-0.4 kg/m(2)), each kg/m(2) increment in BMI was associated with an odds ratio for becoming hypertensive of 1.19 (1.14, 1.24) in men and 1.11 (1.02, 1.20) in women. Thus, even among lean, physically active individuals: (i) weight gain increases hypertension risk; (ii) higher body weight increases the hypertension risk in a dose-dependent manner in the absence of any weight change; and (iii) there is no advantage carried forward to having been previously lean. | 18,756,262 |
Replication licensing and cancer--a fatal entanglement? | Correct regulation of the replication licensing system ensures that chromosomal DNA is precisely duplicated in each cell division cycle. Licensing proteins are inappropriately expressed at an early stage of tumorigenesis in a wide variety of cancers. Here we discuss evidence that misregulation of replication licensing is a consequence of oncogene-induced cell proliferation. This misregulation can cause either under- or over-replication of chromosomal DNA, and could explain the genetic instability commonly seen in cancer cells. | 18,756,287 |
Conjugated linoleic acid and atherosclerosis: studies in animal models. | Conjugated linoleic acids (CLA) are isomeric forms of linoleic acid (LA) containing two conjugated sites of unsaturation. The most abundant dietary form of CLA is the cis-9,trans-11 (c-9,t-11) isomer that is found in the fatty tissues and milk of ruminant animals. CLA can also be acquired by ingestion of supplements, which are usually equimolar mixtures of the c-9,t-11 and t-10,c-12 CLA. For more than a decade, the potential for CLA to modify atherosclerosis in animal models has been examined. However, to date, the studies have failed to reach consensus on whether CLA can be effective in reducing the incidence or severity of atherosclerotic lesions, or whether or not plasma lipid and lipoprotein levels can be improved with CLA supplementation. This review will examine the evidence for and against a role for CLA in atherosclerosis, with a focus on the rabbit, the hamster, and the apoE-deficient mouse. | 18,756,324 |
Cardiovascular outcomes in the comparative hypertension drug trials: more consensus than controversy. | The comparative anti-hypertensive drug trials conducted to assess their cardiovascular protective efficacy actually produce compatible, not conflicting, results. In the last decade, there were 13 major comparative hypertension drug trials with the cardiovascular primary outcome being statistically equivalent in 11 of these 13 trials, involving over 90 percent of the randomised 168,593 patients. Where secondary outcomes favour a drug in these trials, that arm has a significantly lower treated blood pressure as in LIFE, VALUE, ASCOT and ALLHAT. Controversy occurs in seeking to attribute the benefit to drug effect; if the benefit is attributed to the lower achieved blood pressure, then the trials become consistent. The safety and value of diuretics, beta-blockers, calcium-blockers, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in reducing blood pressure, and in reducing clinical cardiovascular outcomes, is now clearly established. Overall, the importance of tight blood pressure control in reducing cardiovascular outcomes must be emphasised. Physicians should concentrate on achieving good blood pressure control, which often requires a combination of several antihypertensive drugs. | 18,756,340 |
The alteration of plasma's zinc and copper levels in patients with burn injuries and the relationship to the time after burn injuries. | Burn injury is a medical problem as well as a social burden on the national health services in developing countries. Trace elements have important roles in wound healing and act as antioxidants. In this study, zinc (Zn) and copper (Cu) levels in plasma of burned patients and their relationship with the burn surface area and time-related pattern are determined in the admitted patients after burn injury. 37 patients were divided into two groups: Group 1 consisted of 16 patients with burn injuries less than 20 percent of the total burn surface area, and Group 2 consisted of 21 patients with burn injuries between 20 and 40 percent of the total burn surface area. The control group consisted of 20 subjects. The Zn and Cu levels were determined one, three, seven and 14 days after the occurrence of burn injury. These trace elements were determined using atomic absorption spectrophotometer. These trace elements in plasma significantly decreased on all days after admission and the levels were lower than those of the control group. There was no significant relationship between Groups 1 and 2 in Cu and Zn concentrations on different days. We did not find any difference between burn surface area and Zn and Cu concentrations in these groups. Based on the critical role of plasma's Zn and Cu rate in wound healing and their relationship in decreasing the burn injury, it is important that patients having burn types II and III take Zn and Cu supplements continuously as micronutrients after burn injury. | 18,756,346 |
Static and moving phantom studies for radiation treatment planning in a positron emission tomography and computed tomography (PET/CT) system. | To determine an appropriate threshold value for delineation of the target in positron emission tomography (PET) and to investigate whether PET can delineate an internal target volume (ITV), a series of phantom studies were performed. An ellipse phantom (background) was filled with 1028 Bq/ml of [(18)F] fluoro-2-deoxyglucose ((18)FDG), and six spheres of 10 mm, 13 mm, 17 mm, 22 mm, 28 mm, and 37 mm in diameter inside it were filled with (18)FDG activity to achieve source-to-background (S/B) ratios of 10, 15, and 20. In static phantom experiments, an appropriate threshold value was determined so that the size of PET delineation fits to an actual sphere. In moving phantom experiments with total translations of 10 mm, 20 mm, and 30 mm and a period of oscillation of 4 s, the maximum size of PET delineation with the appropriate threshold value was measured in both the axial and sagittal planes. In the static phantom experiments, the measured maximum (18)FDG activities of spheres of less than 22 mm were lower than 80% of the injected (18)FDG activity, and those for the larger spheres ranged from 90% to 110%. Appropriate threshold values determined for the spheres of 22 mm or more ranged from 30% to 40% of the maximum (18)FDG activity, independent of the S/B ratio. Therefore, we adopted an appropriate threshold value as 35% of the measured maximum (18)FDG activity. In moving phantom experiments, the maximum (18)FDG activity of spheres decreased significantly, dependent on the movement distance. Although the sizes of PET delineation with 35% threshold value tended to be slightly smaller (<3 mm) than the actual spheres in the axial plane, the longest sizes in the sagittal plane were larger than the actual spheres. When a threshold value of 35% of the measured maximum (18)FDG activity was adopted, the sizes of PET delineation were almost the same for static and moving phantom spheres of 22 mm or more in the axial plane. In addition, PET images have the potential to provide an individualized ITV. | 18,756,360 |
The clinical efficacy of (18)F-FDG-PET/CT in benign and malignant musculoskeletal tumors. | Most of the current clinical data on the role of 2-[(18)F]fluoro-2-deoxy-D -glucose positron emission tomography ((18)F-FDG-PET) in musculoskeletal tumors come from patients studied with PET and less frequently with hardware fusion PET/computed tomography (CT). And the number of cases in each report is too small to clarify the exact clinical efficacy of PET or PET/CT. This prompted us to analyze our experience with (18)F-FDG-PET/CT in a relatively large group of patients with musculoskeletal tumors. (18)F-FDG-PET/CT was performed on 91 patients from May 2004 to June 2007. The final diagnosis was obtained from surgical biopsy in 83 patients (91%) and clinical follow-up in 8 (9%). We analyzed the characteristics and amount of (18)F-FDG uptake in soft tissue and bone tumors, and investigated the ability of (18)F-FDG-PET/CT to differentiate malignant from benign tumors. The cutoff maximum standardized uptake value (SUV(max)) was calculated using the receiver-operation characteristic curve method. Sensitivity, specificity, and diagnostic accuracy were calculated with cutoff SUV(max) and the final diagnosis. Unpaired t test was used for the statistical analysis. Final diagnosis revealed 19 benign soft tissue tumors (mean SUV(max) 4.7), 27 benign bone tumors (5.1), 25 malignant soft tissue tumors (8.8), and 20 malignant bone tumors (10.8). There was a significant difference in SUV(max) between benign and malignant musculoskeletal tumors in total (P < 0.002), soft tissue tumors (P < 0.05), and bone tumors (P < 0.02). Sensitivity, specificity, and diagnostic accuracy were 80%, 65.2%, and 73% in total with cutoff SUV(max) 3.8, 80%, 68.4%, and 75% in the soft tissue tumors with cutoff SUV(max) 3.8, and 80%, 63%, and 70% in the bone tumors with cutoff SUV(max) 3.7. (18)F-FDG-PET/CT reliably differentiated malignant soft tissue and bone tumors from benign ones, although there were many false-positive and false negative lesions. Further studies with all kinds of musculoskeletal tumors in large numbers are needed to improve the diagnostic accuracy of (18)F-FDG-PET/CT. | 18,756,363 |
Detection of a suspected bronchobiliary fistula by hepatobiliary scintigraphy. | Bronchobiliary fistula (BBF) represents a rare but severe complication in patients affected by liver metastases. Although a clinical suspicion can arise when specific clinical signs, in particular biliptysis, are present, conventional imaging modalities often fail to confirm the diagnosis. We present a case of a patient affected by colon cancer with liver metastases previously treated with partial right-sided hepatectomy and multiple thermo-ablative treatments combined with chemotherapy, who manifested a septic fever associated with productive cough and biliptysis. Diagnosis of BBF was confirmed only by hepatobiliary scintigraphy with (99m)Tc-heptoiminodiacetic acid. | 18,756,368 |
Conscientious refusal by physicians and pharmacists: who is obligated to do what, and why? | Some medical services have long generated deep moral controversy within the medical profession as well as in broader society and have led to conscientious refusals by some physicians to provide those services to their patients. More recently, pharmacists in a number of states have refused on grounds of conscience to fill legal prescriptions for their customers. This paper assesses these controversies. First, I offer a brief account of the basis and limits of the claim to be free to act on one's conscience. Second, I sketch an account of the basis of the medical and pharmacy professions' responsibilities and the process by which they are specified and change over time. Third, I then set out and defend what I call the "conventional compromise" as a reasonable accommodation to conflicts between these professions' responsibilities and the moral integrity of their individual members. Finally, I take up and reject the complicity objection to the conventional compromise. Put together, this provides my answer to the question posed in the title of my paper: "Conscientious refusal by physicians and pharmacists: who is obligated to do what, and why?". | 18,756,375 |
Elekta Precise Table characteristics of IGRT remote table positioning. | Cone beam CT is a powerful tool to ensure an optimum patient positioning in radiotherapy. When cone beam CT scan of a patient is acquired, scan data of the patient are compared and evaluated against a reference image set and patient position offset is calculated. Via the linac control system, the patient is moved to correct for position offset and treatment starts. This procedure requires a reliable system for movement of patient. In this work we present a new method to characterize the reproducibility, linearity and accuracy in table positioning. The method applies to all treatment tables used in radiotherapy. The table characteristics are investigated on our two recent Elekta Synergy Platforms equipped with Precise Table installed in a shallow pit concrete cavity. Remote positioning of the table uses the auto set-up (ASU) feature in the linac control system software Desktop Pro R6.1. The ASU is used clinically to correct for patient positioning offset calculated via cone beam CT (XVI)-software. High precision steel rulers and a USB-microscope has been used to detect the relative table position in vertical, lateral and longitudinal direction. The effect of patient is simulated by applying external load on the iBEAM table top. For each table position an image is exposed of the ruler and display values of actual table position in the linac control system is read out. The table is moved in full range in lateral direction (50 cm) and longitudinal direction (100 cm) while in vertical direction a limited range is used (40 cm). Our results show a linear relation between linac control system read out and measured position. Effects of imperfect calibration are seen. A reproducibility within a standard deviation of 0.22 mm in lateral and longitudinal directions while within 0.43 mm in vertical direction has been observed. The usage of XVI requires knowledge of the characteristics of remote table positioning. It is our opinion that the method presented meets the requirements in high precision IGRT. | 18,756,401 |
Tranilast: a pharmaceutical candidate for reduction of adhesions using a novel approach. | Postsurgical adhesion formation has numerous deleterious side effects in a wide variety of surgical settings. Physical barriers used together with laparoscopy were developed in hopes of reducing the tissue trauma seen with open procedures and separating tissues during the critical time of healing to reduce adhesion formation. Despite meticulous techniques by surgeons and the availability of barriers, adhesion formation remains a serious problem, with more than $1 billion spent annually on complications arising from adhesions. Our laboratories have combined a previously marketed drug, Tranilast, with a gel to provide a locally delivered medicated device that can reduce adhesion formation. This article will review the role of Tranilast in the key pathways involved in adhesion formation. | 18,756,411 |
The concept of endophenotypes in psychiatric diseases meeting the expectations? | Although the prominent role of genetics in psychiatric diseases has been established in various family, twin and adoption studies over the last decades, the identification of concrete contributing genes has been demanding. The reasons for this are manifold, including inconsistencies in psychiatric classification systems, complexity and heterogeneity of psychiatric disorders, epistatic effects and intervening environmental factors. In recent years interest has focused increasingly on the concept of endophenotypes. Genetic analyses have concentrated on discrete phenotypes supposedly linked to a particular psychiatric disorder by common neurobiological pathways, instead of studying the complex disease itself. Several endophenotypes have been established for psychiatric diseases including electrophysiological abnormalities and alterations in structural and functional brain imaging. Although results seem to be getting more consistent and reliable, several concerns have also emerged with the experience gained on the topic. This review will give an overview of the prospects and limitations related to endophenotypes in psychiatric diseases. We will also summarize essential prerequisites for successful endophenotypes in the future as well as applications for psychiatric diseases which have been envisioned. | 18,756,419 |
[Efficacy of pegylated interferon alpha-2a and ribavirin treatment in chronic hepatitis C patients depends on various baseline parameters and early viral kinetics]. | The aim of the study was to compare efficacy and viral kinetics during antiviral treatment in different chronic hepatitis C patients--naïve, relapsers and non-responders to previous pegylated interferon alpha (PEG-IFN) and ribavirin treatment, with different genotypes, baseline viremia, body weight, age and gender--and to find some baseline parameters which can predict Sustained Virological Response (SVR; negative serum HCV RNA 24 weeks after treatment). 216 chronic hepatitis C patients were treated with PEG-IFN alpha-2a 180 mg/wk and ribavirin 1 000 or 1 200 mg/day. There were 140 men and 76 women, mean age 40, range 19-70 years; 142 (66 %) naïve, 37 (17 %) relapsers after previous PEG-IFN and ribavirin treatment, and 37 (17 %) non-responders to this treatment. 172 (79,6%) has genotype 1 infection, 4 (1,9 %) genotype 2, 34 (15,6 %) genotype 3, 1 (0,5 %) genotype 4 or 6 infection, and 4 (1,9 %) were infected by unknown viral genotype. Quantitative detection of HCV RNA was done at baseline (216 pts.), 24 hours (83 pts.), 14 days (85 pts.), 28 days (88 pts.), and 84 days (211 pts.) after the first dose of PEG-IFN. 195 patients have completed the treatment period and 179 patients the 24-week follow-up period. The probability of SVR was significantly higher (P < 0,001) in naïve patients (74/114, 64,9 %) and relapsers (22/30, 73,3 %) than in non-responders (9/35, 25,7 %) and in genotype 3 patients (23/28, 82,1%) than genotype 1 patient (77/143, 53,8 %) (P = 0,002). The patients with SVR comparing those without SVR have significantly lower weight (mean 72,8 kg vs. 79,1, P = 0,008(, were younger (mean 36,2, vs. 45,5, P > 0,001), and had lower baseline viremia (mean 1,014 3 106 IU/mL vs. 2,415 3 106 IU/mL, P > 0,001). SVR was more frequent in women than in men (43/63, 62,8 % vs. 62/116, 53,4 %) but difference was not significant (P = 0,059). Undetectable serum HCV RNA at week 12 was more predictive of SVR than early viral response (minimum 2 log decrease of serum HCV RNA during the first 12 weeks of treatment)--98/122 (80,3 %) versus 104/141 (73,1 %) of SVR. 1) The monitoring of viral kinetics during first 12 weeks of antiviral therapy in hepatitis C patients was an important predictive value for SVR. 2) Negative serum HCV RNA at week 12 was more predictive of SVR than early viral response. 3) The probability of SVR was significantly higher in patients with lower baseline viremia, body weight and younger adults. 4) Gender was not significant for the efficacy of treatment. | 18,756,436 |
Manganese-enhanced MRI of acute cardiac ischemia and chronic infarction in pig hearts: kinetic analysis of enhancement development. | To assess infarction development in pig hearts, Mn-enhanced and Gd-enhanced MRI were used. In domestic pigs (25-35 kg, n = 37), the first and second diagonal branches of the left anterior descending coronary artery were ligated to induce acute ischemia and infarction (ischemia+reperfusion) or chronic infarction of increasing duration (3- 28 days). Ex vivo experiments were performed on hearts perfused in the Langendorff mode with a 50:50 mixture of blood and Krebs-Henseleit buffer using a spin-echo sequence on a 7 T Bruker imaging system. Signal acquisition from the heart and two reference test tubes (H(2)O and H(2)O + 10 mM CuSO(4)) was gated by the left ventricular pressure wave. T(1)-weighted images of six 8 mm short-axis slices (2 mm interslice gaps) were obtained before and after the addition of 0.2 mM MnCl(2) every 5 min over a 30-45 min period. Signal intensities were normalized to those of the H(2)O reference and fitted by a monoexponential function. The rates of intensity increase and maximal increases were significantly lower in the ischemic/infarcted areas and showed a trend to rise on infarction progression. In vivo Gd-enhanced MRI (3 T Siemens scanner) and in vivo/ex vivo near-infrared imaging confirmed major Mn-enhanced MRI findings. Triphenyltetrazolium chloride staining revealed necrotic areas in all chronic infarctions and no necrosis after acute ischemia. We conclude that MnCl(2) highlights ischemic areas because of the low collateral flow characteristic of pig hearts, whereas in the infarcted areas with substantial perfusion, scar tissue components are important for contrast distribution. | 18,756,440 |
Distinctions between fetal and adult human platelet-derived growth factor-responsive neural precursors. | Platelet-derived growth factor (PDGF)-responsive neural precursors (PRPs; also known as oligodendrocyte progenitor cells) are one of the best characterized precursor cell populations of the rodent central nervous system. Yet little is known about the biology of human PRPs because of an apparent inability to culture and expand them in large numbers. This study was designed to establish an approach that allows direct comparisons between the biology of fetal and adult human PRPs, as a means to address potential differences in intrinsic myelin-production capabilities. We used the neurosphere culture system, under low plating density, to isolate, culture, and compare the properties of fetal and adult human PRPs. PDGF stimulated fetal human PRPs to generate neurospheres that differentiated primarily into oligodendrocytes, which acquired myelin basic protein expression, as well as neurons and a small number of astrocytes. Together with PDGF, fibroblast growth factor 2 promoted fetal human PRP expansion. In contrast, adult human PRPs isolated from the corpus callosum required twice the culture period to generate neurospheres, which contained oligodendrocytes, as well as astrocytes, but not neurons. Strikingly, fibroblast growth factor 2 did not promote adult human PRP self-renewal. Differences in the intrinsic proliferation, phenotype, and self-renewal properties of fetal and adult human PRPs suggest they are distinct populations, which may result in distinct myelin-production capabilities. | 18,756,507 |
HIV-associated plasmablastic lymphoma: lessons learned from 112 published cases. | Plasmablastic lymphoma (PBL) is a distinct subtype of non-Hodgkin B-cell lymphoma, originally described with a strong predilection to the oral cavity of human immunodeficiency virus (HIV)-infected individuals. Data regarding patient age and gender, HIV status, initiation of and response to highly active antiretroviral therapy (HAART), tumor extent, pathology, treatment, and outcome were extracted from 112 cases of PBL identified in the literature. The median age at presentation was 38 years with a male predominance of 7:1, and the median CD4+ count was 178 cells/mm(3). PBL presented on average 5 years after diagnosis of HIV. Common primary sites of presentation included the oral cavity, gastrointestinal tract, and lymph nodes. Most cases presented with either stage I or stage IV disease. There was a variable expression of B-cell markers in tumor cells, but plasma cell markers were expressed in all cases. EBV was detected in 74%. Chemotherapy was used to treat 55% patients and was combined with radiotherapy in 21% cases. Complete response was obtained in 66% of treated cases; the majority of these responses were seen after CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). The refractory/relapsed disease rate was 54%. Death occurred in 53% of patients, with a median overall survival of 15 months. Sex, CD4+ count, viral load, clinical stage, EBV status, primary site of involvement, and use of CHOP failed to show an association with survival. PBL is an aggressive B-cell lymphoma that presents in both oral and extra-oral sites of chronically HIV-infected immunosuppressed young men. | 18,756,521 |
Discovery of water-soluble antioxidant flavonols without vasorelaxant activity. | 3',4'-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that can decrease ischaemia/reperfusion injury in the heart. DiOHF exhibits antioxidant and vasorelaxant properties that are thought to underlie its cardioprotective activity. A major limitation to its use for the treatment or prevention of cardiovascular disease is its poor water solubility, preventing intravenous administration at the required dosage. In this study, three novel flavonols were synthesised that bear an ionisable succinamic acid substituent at the 6-position of the A ring with zero, one, or two hydroxy groups on the B ring. The ionised compounds possess improved aqueous solubility, dissolving at concentrations up to 10(-1) m, whereas DiOHF is insoluble in water (<10(-7) m). Pharmacological analysis revealed that the DiOHF-6-succinamic acid derivative was the best antioxidant, possessing activity similar to DiOHF, whereas vasorelaxant activity was attenuated. This compound was able to effectively scavenge superoxide from the autoxidation of pyrogallol, preventing oxidant-induced endothelial dysfunction. DiOHF-6-succinamic acid represents the first antioxidant flavonol that lacks vasorelaxant activity and in the future will enable studies to cast light on the specific biological activity required for cardioprotection. | 18,756,557 |
No indications of cognitive side-effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy. | A number of cross-sectional studies have reported reduced cognitive function in cancer patients receiving chemotherapy compared with other cancer patients and healthy controls, suggesting that chemotherapy could be associated with cognitive side-effects. Recently published prospective studies question this hypothesis, but it is still unclear whether cancer patients should regard cognitive problems as a potential risk when receiving chemotherapy. In the present study we examine whether cancer patients (n=34) receiving chemotherapy differed in cognitive changes during treatment compared with cardiac patients (n=12) and healthy controls (n=12) tested at 3-4 months interval. Our results showed no differences with respect to changes in cognitive performance over time between cancer patients in chemotherapy, cardiac patients, and healthy controls. In addition, the number of individuals showing reliable decline or improvement on cognitive tests did not differ between groups. Taken together, our results do not support a hypothesis of cognitive side-effects of standard-dose chemotherapy in breast cancer patients. | 18,756,583 |
OCTN and CARD15 gene polymorphism in Chinese patients with inflammatory bowel disease. | To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672C/T and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). A total of 61 patients with Crohn's disease (CD), 151 patients with ulcerative colitis (UC), and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction (PCR-SSP) or by restriction fragment length polymorphism (PCR-RFLP) analysis. Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 (0/61 with CD) and 1.3% (2/151 with UC). Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients. | 18,756,601 |
Compression anastomosis clip for gastrointestinal anastomosis. | To investigate the feasibility of compression anastomosis clip (CAC) for gastrointestinal anastomosis proximal to the ileocecal junction. Sixty-six patients undergoing gastrointestinal anastomosis proximal to the ileocecal junction were randomized into two groups according to the anastomotic method, CAC or stapler. The postoperative recovery of patients in CAC and stapled anastomosis groups was similar. No postoperative complication related to the anastomotic method was found in either group. Both upper gastrointestinal contrast radiography at the early postoperative course and endoscopic examination after a 6-mo follow-up showed a better healing at the compression anastomosis. CAC can be used not only in colonic surgery but also in gastrointestinal anastomosis. Our result strongly suggests that CAC anastomosis is safe in various complication circumstances. However, it should be further confirmed with a larger patient sample. | 18,756,603 |
Laparoscopic resection for incidentally detected Meckel diverticulum. | The management of Meckel diverticulum found unexpectedly during an abdominal operation remains controversial. Most published reports have included only patients undergoing diverticulectomy or bowel resection through laparotomy. We report a case of a carcinoid tumor in a Meckel's diverticulum which was incidentally detected and removed during laparoscopic inguinal hernia repair. Although there is no compelling evidence in the literature to recommend prophylactic diverticulectomy, laparoscopic stapled resection represents a viable and safe approach in healthy individuals undergoing elective surgery for other purposes. | 18,756,607 |
Primary malignant melanoma of the liver: a case report. | Primary malignant melanoma of the liver is an exceedingly rare tumor. Only 12 cases have been reported in the worldwide literature. We present a case of isolated malignant melanoma of the liver occurring in a 36-year-old Chinese male patient. Comprehensive dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or ocular primary lesion. Other lesions in brain, respiratory tract, lung, gastrointestinal tract and anus, were not demonstrated by serial position emission tomography (PET). Microscopic examination of the resected specimen revealed a malignant melanoma, which was confirmed by immunohistochemical staining for HMB-45, S-100 protein, melanoma-pan and vimentin. Moreover, electron microscopy demonstrated melanosomes in tumor cell cytoplasm. Our case shows that primary malignant melanoma may occur in the liver and should be considered when the histopathological appearance is not typical for other hepatic neoplasm. | 18,756,609 |
The use of therapeutic hypothermia after cardiopulmonary arrest. | Actually recommended by the International Liaison Committee on Resuscitation (ILCOR), therapeutic hypothermia has been the only modality shown to improve neurological outcomes after cardiac arrest. This article provides the background for such recommendations as well as: pathophysiology, review of brain injury during cardiac arrest, discussion of beneficial effects of therapeutic hypothermia, different mechanisms used to induce it and the latest clinical trials results. | 18,756,644 |
Can etomidate have antiarrhythmic properties? | Etomidate is a drug commonly used for Rapid Sequence Intubation (RSI) and Procedural Sedation Anesthesia (PSA) in the Emergency Department because of its rapid onset of action and low cardiovascular risk profile. The antiarrhythmic effects of etomidate are presented in a patient with unstable wide complex tachycardia, which converted to sinus rhythm immediately after its administration. This is the first case in the Emergency Medicine literature and the second case reported of possible antiarrhythmic effects of etomidate since its development. | 18,756,645 |
Predictive role of the lambda ratio in the evaluation of metal-on-metal total hip replacement. | The wear of metal-on-metal bearings is affected by various design parameters, such as the clearance or surface roughness. It would be very useful to have a significant indicator of wear according to these design parameters, such as the lambda ratio. Three different batches of cast high- and low-carbon cobalt-chromium hip implants (28 mm, 32 mm, and 36 mm diameters) were tested in a hip joint simulator for 2 x 10(6) cycles. Bovine calf serum was used as lubricant, and the samples were weighed at regular intervals during the test. The predictive role of the lambda ratio on the wear behaviour was investigated. Three different configurations were tested to explore the wear rate for a broad range of lambda ratios. The results of these studies clearly showed that the femoral heads of 36 mm diameter had the best wear behaviour with respect to the other two smaller configurations tested. From a predictive point of view, the lambda ratios associated with the configurations tested could clearly indicate that the femoral heads of 36 mm diameter worked in the mixed-lubrication regime (lambda > 1); all the smallest configurations (28mm size) had lambda < 1, thus showing their aptitude to work in the boundary lubrication regime, with substantially higher volume depletion due to wear. The lambda values associated with the 32 mm size varied in a range around 1 (0.95 < lambda < 1.16), suggesting the possibility of operating in the mixed-lubrication regime. | 18,756,681 |
Dynamic simulation of a displacement-controlled total knee replacement wear tester. | This paper presents a dynamic finite element method (FEM) model of a commercial displacement-controlled total knee replacement (TKR) wear tester. The first goal of the study was to validate the model, which included both the wear tester and the TKR components. Convergence simulations and experimental testing were performed. These included a novel experimental determination of the coefficient of friction and an evaluation of predicted joint contact areas by comparing simulation results with experimental data collected using pressure-sensitive film. The second goal of this study was to develop a procedure for implementing force-based testing protocols on a displacement-controlled TKR wear tester. A standard force-based cyclic wear-testing protocol was simulated using the FEM model and resulting displacement waveforms were extracted. These were used as control inputs to the physical wear tester and an experimental wear test was performed. Reaction loads on the tibial components were measured and compared with the simulated results. The model was capable of accurately predicting the tibial loads throughout the test cycle, verifying the model's contact mechanics. The study demonstrated the use of computational modelling to convert a force-based testing protocol into displacement-based control parameters for use in a displacement-controlled mechanical testing system. | 18,756,686 |
[Hyper- and hypoaldosteronism]. | The literature review devoted to pathogenesis of the development of hyper- and hypoaldosteronism is presented. Based on the analysis of Russian and English-written literature known and clinically significant diseases arising due to hyper- and hypoaldosteronism are presented. Pathogenetic mechanisms inducing the development of primary and secondary forms of hyper- and hypoaldosteronism were enlightened. Furthermore the data on mechanisms of formation of hyper- and hypoaldosteronism are given. | 18,756,739 |
[Study of ethno-racial and sexual specificity of hard palate mucosa for person identification]. | Relief of hard palatal mucosa was examined to identify ethno-racial and gender affiliation in representatives of europeoid, mongolid, and intermediate racial groups, viz Estonians (northern europeoid type), Azerbajaninans (southern europeoid), Koreans (Far East mongoloid), and Kasakhs (intermediate). The results of the study suggest the possibility in principle to identify the ethno-racial affiliation of human subjects from the distribution pattern of hard palate mucosal folds. | 18,756,758 |
[Medical geography in study of rickettsioses]. | Shorts resume of medical-geographical studies of Q-fever, tsutsugamushi fever, rickettsioses of tick-borne spotted fever is represented. Influence of biotic and abiotic factors on spread and landscape tropism of infection agents is considered. Types of focuses on endemic territories are determined, regions with high risk of infection for humans are detected. | 18,756,781 |
[Scientific collaboration of Russia and France in the study of ricketsioses]. | The description of emerging diseases unknown for the scientists before 90th has begun by the cooperative description of Astrakhan spotted fever by Irina Tarasevich and Didier Raoult. Molecular methods gave the possibility to distinguish its etiological agent from other rickettsiae and to prove that it differs from all other species, so this gave the background to describe the new disease. At the same time, this event promoted the collaboration between Russian and French groups of rickettsiologists. Collaborative studies of both groups in addition provoked the proposed idea of species criteria in rickettsioigy, that, in its turn, gave the way to revealing multiple novel rickettsiae and rickettsioses. I. Tarasevich created the stable cooperation with D. Raoult and this cooperation spread for all laboratories also. So, Oleg Mediannikov, Stan Shpynov, Anna Evstigneeva are always welcome in Marseille. Prolonged recently Cooperation Agreement between Gamaleya Institute and Universite de Mediterranee has brought already fine results and, hopefully, will bring yet the continuation of scientific and close friendly relationship. | 18,756,786 |
[Effect of fluorinated silicone oil on the rabbit retinal antioxidant status]. | The high-grade fluorinated silicone oil made in Russia was tested for its effect on the rabbit retinal antioxidant status. Experiments were made on 36 rabbits (72 eyes) undergoing replacement of the excised vitreous body with sterile 0.9 NaCl solution or with one of the study implants (fluorinated silicon oil, silicon oil, or perfluorodecahydronaphthalene) after subtotal vitrectomy. The impact of the study implants on the rabbit retinal antioxidant status was postoperattively investigated. The experimental findings suggest that the high-grade fluorinated silicon oil made in Russia may be used as an implant for short-term vitreous chamber tamponade. | 18,756,801 |
[Epidemic strains influenza viruses A and B in the 2005-2006 season in Russia]. | Investigations indicated that the epidemic upsurge of influenza morbidity in the 2005-2006 season in Russia was caused by the active circulation of influenza viruses A and B. The Center for Ecology and Epidemiology of Influenza, D. I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, studied 182 epidemic strains. A hundred and thirteen influenza viruses A(H3N2) were similar to the reference A/California/07/2004 or were its antigenic variants. Thirteen influenza virus A(H1N1) strains that were antigenic variants of the reference A/New Caledonia/20/99 were isolated in sporadic cases. Influenza viruses B were similar to B/Malaysia/2506/2004--lineage B/Victoria/2/87). All the strains were isolated in the MDCK cell culture. Comparative study of the sensitivity of the chicken embryo (CE) and MDCK isolation system to the 1999-2006 epidemic strains showed that CE tropism was least pronounced in influenza viruses A(H3N2). Analysis of the 2002-2006 strains demonstrated that influenza viruses A reacted actively with human erythrocytes of the blood groups 0(I) and A(II) and very slightly with chicken ones. Eighty-five influenza virus A(H3N2) strains from the 2005-2006 epidemic season were investigated for rimantadine susceptibility. The frequency of rimantadine-resistant influenza virus A(H3N2) strains was 38.0%. Studies of 79 paired sera from patients revealed a rise of antibodies to influenza viruses A(H3N2) and B in 25.9-33.3 and 20.7-23.8% of cases, respectively. There was an increase in antibodies to influenza viruses A and B in the sera collected from donors in Moscow and its region in September 2005 to June 2006. | 18,756,810 |
[Production of human recombinant beta-interferon in the avian cell culture]. | The avian recombinant adenovirus of serotype 1 (CELO) was obtained. The recombinant adenovirus of serotype 1 (CELO) induces expression of human beta-interferon (IB). The expression cassette containing IB gene was placed at the right end of the CELO genome under control of hybrid promoter hEF-1alpha/HTLV. The resulting recombinant adenovirus CELO-IB transduced the avian cell culture LMH. The level of production of the recombinant IB was 0.15 micro/ml. The IB protein yield after affine chromatography purification using Ni-NTA agarose was 50%. The biological activity of the purified IB was high (7.8 x 10(8) MU/microg protein). The purified IB inhibited replication of murine encephalomyocarditis virus (VMEC) in cell culture of human diploid fibroblasts (HDF). Thus, expression system based on avian cell culture is an effective system for producing biologically active protein of human interferon beta. | 18,756,823 |
[Serum levels of ghrelin and leptin in women with polycystic ovary syndrome]. | To compare ghrelin and leptin levels in women with PCOS and healthy subjects and to evaluate the relationship between them and the heterogeneity of clinical and biochemical manifestations of women with polycystic ovary syndrome (PCOS). 45 women with PCOS and 20 controls were included in the study. Serum levels of ghrelin, leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, LH and FSH were measured. Free androgen index (FAI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed. Serum ghrelin levels in PCOS patients were lower (21.78 +/- 2.12 ng/ml vs. 34.67 +/- 3.57 ng/ml; p = 0.04) and leptin levels were higher (15,03 +/- 2,9 ng/ml vs. 6,16 +/- 0,60 ng/ml p = 0,048) than the control group. In group with PCOS negative correlation exists between ghrelin and testosterone (r = -0.315; p < 0.05) and between ghrelin and leptin levels (r = -0.306; p < 0.05). The latter correlation disappeared after partial correlation analysis controlling for BMI, WHR and HOMA-IR. In PCOS patients there were strong positive correlation between leptin and IRI (r = 0.592, p < 0.01) and HOMA-IR (r = 0.637, p< 0.01). In PCOS patients with more pronounced insulin resistance the correlation between leptin levels and HOMA-IR is independent of BMI, WHR and waist circumference. Our study confirms the strong association that exists between serum leptin levels and clinical and hormonal indices of IR. The ghrelin level in women with PCOS reflects the metabolic and hormonal changes which are characteristics of the syndrome. The inverse correlation between ghrelin and leptin in these women is mediated through metabolic factors. | 18,756,827 |
Identifying serious causes of back pain: cancer, infection, fracture. | Most patients with back pain have a benign condition, but tumors, infections, and fractures must be considered during an initial evaluation because overlooking them can have serious consequences. This article discusses the presentation and diagnostic strategies of these serious causes of back pain. | 18,756,836 |
Adherence to highly active antiretroviral therapy (HAAT) at a Federal Medical Centre. | Highly active antiretroviral therapy (HAART) has proved effective in prolonging survival and improving the quality of life of the people living with HIV/AIDS (PLWHA). For the successful treatment of HIV infection, at least 95% adherence to HAART is required. This study sought to assess adherence to HAART and to identify factors enhancing adherence within the study population. The study was a descriptive cross-sectional survey of 428 patients attending the antiretroviral (ARV) clinic of the Federal Medical Centre, Makurdi. Self-reported adherence and other data were collected using an interviewer-administered questionnaire. Data were analysed using SPSS 11.0 and Epi6; and were exported into Systat 11 for multivariate logistic regression. There were 151 (35.3%) males and 277 (64.7%) females. The mean age was 36.7 +/- 9.6 years. Self-reported adherence rate was 268 (62.6%). The factor most predictive of adherence to HAART was availability of ARVs [OR = 5.2; 95% confidence interval 3.1-8.6; p < 0.001], followed by the ability to afford regular visits to the ARV clinic [OR = 1.7; 95% confidence interval 1.04-2.8; p = 0.034]. A recent diagnosis of HIV made less than 3 years prior to the study period was also significantly associated with adherence to HAART (chi2 = 8.94; p = 0.003). Availability of ARVs and ability to afford to regularly visit the clinic among other factors, positively influenced adherence to HAART among PLWHA. Efforts should be targeted at constant provision of free ARVs and early initiation of therapy for those requiring treatment, as well as ensuring regular adherence-education. | 18,756,852 |
Anxiolytic and sedative effects of extracts of Hibiscus sabdariffa Linn (family Malvaceae). | Aqueous (A), hydroalcoholic (AE) and ethanolic (E) extracts and fractions of dried calyxes of Hibiscus sabdariffa were evaluated for anxiolytic property using elevated-plus maze (EPM), and sedative properties using ketamine-induced sleep in animal models. The extracts exhibited a dose-dependent increase in the time spent in the open arm with ethanol extracts having the best anxiolytic activity. The extracts at A 5 mg/kg, AE 5 mg/kg and A 50 mg/kg did not cause an increase in time spent in the open arms (p < 0.05) but other doses significantly did when compared with the vehicle control. The fractions of the hydroalcoholic extracts showed no significant anxiolytic activity. Neither the extracts nor the fractions significantly reduced or increased latency to sleep after a single dose except AE 300 (p < 0.01). There was significant reduction in onset of sleep, and increase in sleeping time with A and AE extracts with multiple doses at A 300, AE 50 and AE 300 mg/kg dose groups (p < 0.001, p < 0.01 and p < 0.05 respectively). A reduction in sleeping time after several daily doses of ethanol extracts doses was observed. A single dose of one of the fractions (EAC at 50 mg/kg) caused a significant reduction (p < 0.05) in sleep duration. The study showed that extracts of Hibiscus sabdariffa possess anxiolytic and sedative effects which become more pronounced with administration of repeated doses of the extracts. | 18,756,855 |
Accidental displacement of mandibular third molar into soft tissue: a case report. | A case of accidental displacement of a mandibular molar tooth into adjacent submandibular space during routine extraction by a general practitioner is reported. The localization and surgical retrieval of the displaced tooth is described, post-operative period was uneventful and salient lessons for the practitioners highlighted. | 18,756,859 |
Cell apoptosis as assessed by M30 expression in keratoacanthoma and squamous cell carcinoma. | Involution displayed by keratoacanthoma (KA) represents an important difference between KA and squamous cell carcinoma (SCC). It has been suggested that apoptosis plays a part in process of involution of KA. Altogether 150 specimens were included in this study, 30 cases of each; normal skin (NS), proliferative (pKA) and regressing keratoacanthoma (rKA), well differentiated (wdSCC) and poorly differentiated (pdSCC) squamous cell carcinoma. All samples were examined immunohistochemically for expression of M30 protein. A significantly lower number of M30 positive cells has been detected in NS as compared to skin tumors examined (p<0.001), except for rKA (p=0.057). The highest percentage of M30 positive cells was detected in pdSCC (p<0.001) as compared with all other examined groups. Keratinocytes of normal and changed epidermis expressing higher levels of M30 protein were predominately found in sun-exposed areas (chi2=14.93; p=0.060). There was an increasing trend of M30 protein expression with increasing age of the patient in NS and skin tumors examined. Majority of skin tumors with higher percentage of M30 positive cells tended to display higher Ki-67 expression. M30 expression was highly correlated with bak (r=0.811; p=0.048) and granzyme B expression in rKA (r=0.733; p=0.015). Cell apoptosis as assessed by M30 expression is, generally, increased in examined skin tumors and related to cell proliferation. Cell apoptosis mediated by bak and granzyme B expression could contribute to KA regression. | 18,756,900 |
Prognostic significance of BsALP in healing of long bone fractures. | The aim of this work was to assess the relationship of both total alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BsALP) with the course and outcome of operatively treated long-bone fractures. The activity of total ALP and BsALP was measured in 41 patients with a long bone fracture, comprising 26 men and 15 women. All patients were treated operatively. Total ALP and BsALP levels were measured in sera on day 1, 7, 14 and 21 after sustaining injury. Patient monitoring included X-rays. According to the outcome, patients were divided into two groups: the fast healing group and the slow healing group. The levels of total ALP and BsALP showed parallel trends in the course of this study. Depending on the healing outcome, on day 7 an increase in the case of slow healing, or a decrease in the case of fast healing, for both BsALP and total ALP was observed. No difference was found between various sites of bone fracture. This is an important result indicating the prognostic significance of total ALP and BsALP measurement in the monitoring of long bone fracture healing. In addition, an early change in the level of these enzymes was associated with the efficiency of the performed surgery. | 18,756,909 |
A case study of Chinese bound feet: application of footprint analysis. | Foot print patterns of the bound feet of a 90-year-old Chinese female were made to obtain insight into the ergonomic consequences of a Chinese custom that caused significant disabilities for many women throughout history. Pressure patterns were evaluated using the techniques applied to standard thumb print analsyis. A digital summary of the pressure patterns were compared to the patterns obtained from a normal subject. The outcomes indicated that the bound foot produced greater plantar tissue pressures than the non-bound foot. These observations help explain the discomfort, gait abnormalities, and disabilities exhibited by many older women with bound feet living in China today. Although foot-binding is no longer practiced, this study offers an ergonomic perspective on a custom practiced in China for centuries. | 18,756,921 |
[Injection of activated carbon nanoparticles for guiding lymphadenectomy during minimal invasive surgery in lung cancer]. | To evaluate the clinical value of activated carbon nanoparticles for guiding lymphadenectomy in lung cancer. Fourty-two lung cancer patients were divided into two groups: the control group (22 cases) and experiment group (20 cases) who received activated carbon nanoparticles injection around the tumor either by endoscopic injection or intraoperative subserosal injection. The number of dissected lymph node, black-stained lymph node, positive lymph node and the side effect of the procedure were analyzed, respectively. No severe complication was observed in the experiment group. The operative time was not prolonged significantly in the experiment group either. However, the number of average lymph nodes dissected in the experiment group (25.5) was significantly more than that in the control group (14.6) (P <0.01). Local injection of activated carbon nanoparticles around the tumor during surgical exploration is effective, safe and easy to do for guiding lymphadenectomy in lung cancer patient. | 18,756,943 |
[A comparison of localization by ductoscopy-guided wire and conventional methods in terminal duct excision for women with pathological nipple discharge]. | To evaluate and compare localization by ductoscopy-guided wire with localization by conventional methods in the terminal duct excision for women with pathological nipple discharge. Breast terminal duct excision were performed in 174 consecutive patients with intraductal lesions diagnosed by mammary ductoscopy. Sixty-eight of those underwent ductoscopy-guided wire localization for more accurate ductal excision. The patients received mammary ductoscopy and a hooked wire was anchored at the intraductal lesions under endoscopic surveillance just before the operation. Then a biopsy resection of wire-guided terminal duct and frozen section were done. Tbe other 106 patients received terminal duct excision under localization with conventional methods without ductoscopy either by puncturing a needle or injection of blue dye through the duct with pathological discharge. Of the 68 patients with ductoscopy-guided duct excision, 64 had intraductal papillomas and 4 duct carcinoma in situ proved by pathology. All the lesions in these 68 patients were completely resected during biopsy without extra extended resection, and the concordance rate of the pathological result with ductoscopic diagnosis was 100.0%. None of them developed a postoperative breast distortion. In the conventional method localization group, there were 96 intraductal papilloma, 6 duct carcinoma in situ and 4 adenosis. Only 77.4% of the lesions were excised in the primary biopsy, and 22.6% needed extended resection. The concordance rate of the pathological diagnosis with ductoscopic diagnosis was 96.2%. Twenty-six patients had a deformed breast postoperatively. Ductoscopy-guided wire localization is superior to the conventional localization method in the surgical terminal duct excision for women with spontaneous nipple discharge. It is not only helpful for more accurate localization and resection as well as pathologic sampling, but also is minimally invasive. Further studies are still required and this method may deserve to be popularized. | 18,756,945 |
[Feasibility of establishment of rat model of bone cancer pain by using Walker 256 cells cultured in vitro or in vivo]. | To investigate the possibility of establishing rat model of bone cancer pain using cancer cells cultured in vitro or by ascites passaging and verify the reliability of this method. Syngeneic SD rat carcinoma cells of the line Walker 256 were cultured in vitro and inoculated into the peritoneal cavity of SD rats respectively. Two kinds of Walker 256 cell suspension were made. Thirty-two SD rats were randomly divided into 4 equal groups: Group N (undergoing injection of Hank's solution into cavitas medullaris of left tibia), Group K (undergoing injection of heat-killed Walker 256 cells), Group V (injected with Walker 256 cells cultured in vitro), and Group A (injected with Walker 256 cells passaged in ascites). After 6, 12, and 18 days, the rats underwent roentgenography. Radio nuclide emission computed tomography (ECT) was conducted 12 days later. And MRI was conducted 15 days later. Thermal withdrawal latency (TWL) and pressure withdrawal threshold (PWT) were measured. Von Frey threshold and weight bearing of left hind limb were examined. On the 18th day after the establishment of model the rats were killed with their left tibia taken out to undergo microscopy. The rats of Groups A and V began to display decrease of left hint limb activity and roentgenography showed minute defect of bone trabecula in the proximal epiphysis by day 6. By day 12 roentgenography showed multiple defect of bone trabecula, ECT showed reactive bone formation. The rats of Groups A and V displayed signs of weight loss by day 14, and by day 18 roentgenography showed full thickness bicortical bone loss and formation of soft tissue tumor. Histological examination 18 days later revealed that the bones inoculated with live cells showed infiltration of bone marrow spaces by malignant tumor. The PWT values gradually decreased since day 6 to day 18, and the PWT values in this period of Groups A and V were all significantly lower than those of Groups K and N (all P < 0.01). The von Frey values gradually decreased since day 6 to day 18, and the von Frey values in this period of Groups A and V were all significantly lower than those of Groups K and N (all P < 0.01). The weight bearing value of left hind limb gradually decreased and the weight bearing difference between the 2 hind limbs gradually increased since day 6 to day 18, and the values of weight bearing difference between the 2 hind limbs of Groups A and V were significantly higher than those of Groups K and N (all P < 0.01). Sixteen rats underwent subcutaneous injection of morphine, and the PWT values increased 20, 30, and 40 min later in a dose-dependent manner (P < 0.01). Naloxone injected 1 h later antagonized the analgesic effect of morphine. A SD rat model of bone cancer pain has been successfully established by using syngeneic rat bone carcinoma cells cultured in vitro or in vivo, and the latter being more convenient. | 18,756,951 |
[Trans-sacroiliac joint with plate via the anterior approach in management of posterior pelvic injuries]. | To report the clinical experience in trans-sacroiliac joint with plate via the anterior approach in management of posterior pelvic injuries. The clinical data of 29 cases (30 sides) with pelvic injury, 16 being of type B, and 13 of type C according to the Tile classification; with the average displacement of the posterior ring injuries of 18 mm; undergoing trans-sacroiliac joint with plate via the anterior approach from January 2002 to June 2007 were analyzed retrospectively, among which 20 sides were fixed by two plates across the sacroiliac joint and 10 sides by single plate. The anterior pelvic injuries of 22 cases were fixed by plates too. Twenty-one cases were followed up for 35 months on average. The average operation time was 3 hours, and the average blood transfusion was 1200 ml. Reduction was excellent in 23 sides (77%), good in 6 sides (20%), and fair in 1 side (3%). Operative injury of lumbosacral trunk occurred in 3 sides (10%) and operative injury of lateral femoral cutaneous nerve occurred in 7 sides (23%). Intra-operative major hemorrhage occurred in 2 cases. The average outcome score according to the Majeed grading system was 93, and the function results all were excellent or good. Plating the sacroiliac joint through the anterior approach is an effective method for the management of sacroiliac dislocation or trans-iliac fracture dislocation, while the blood loss of the operation is obvious, and the risk of iatrogenic nerve injury is high. | 18,756,955 |
[Diagnostic value of protein tyrosine phosphatase-2beta antibody (IA-2betaA) in type 1 diabetes]. | To explore the prevalence and clinical features of protein tyrosine phosphatase-2beta antibody (IA-2betaA) in type 1 diabetes (T1DM). Four hundred and one T1DM patients and 200 healthy controls were screened for glutamic acid carboxylase antibody (GADA), islet cell antigen-2 (IA-2A), IA-2betaA by radioligand assay. The clinical features of the patients positive in different antibodies were analyzed. Thirty-five of the 401 T1DM patients were positive in IA-2betaA with a positivity rate of 8.7%, significantly higher than that of the normal controls (1.0%, 2/100, P < 0.05). Out of the 35 cases with IA-2betaA positivity, 16 (45.7%) were positive in IA-2A. Among the 401 T1DM patients, IA-2betaA titer was not correlated with IA-2A titer (r = 0.021, P = 0.780). The IA-2betaA positive rate of the age group of 0-9 years was 62.8%, significantly higher than that of the age group > 10 years (19.7%, chi2 = 31.41, P < 0.001); and the IA-2A positive rate of the age group of 0-9 years was 20.0%, significantly higher than that of the age group > 10 years (7.6%, chi2 = 6.11, P < 0.05). GADA was not significantly correlated with age. The age and onset age of the patients positive only in IA-2betaA were 35.5 and 34.0 years respectively, both significantly higher than those of the patients positive only in IA-2A (24.2 and 21.6 years respectively, both P < 0.05). Higher in child-onset T1DM, the prevalence of IA-2betaA positivity decreases with age. IA-2betaA is a practical parameter for identifying autoimmune diabetes. | 18,756,962 |
[A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting]. | To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting. After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction. There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups. Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting. | 18,756,983 |
[The effect of a strategy to improve adherence of irregular non UE citizens to tuberculosis screening in a clinic of Reggio Emilia]. | Latent tubercolar infection in irregular non EU-citizens in Italy is an important issue of public health. Aim of this paper is to describe the effects of a new organization of the Centre for the health of foreign families of Reggio Emilia. A dedicated nurse, responsible of patients' screening and follow-up, in strict collaboration with a cultural interpreter were made available. Patients adherence to the screening was measured. On 177 eligible patients, 12 (6.7%) refused the Mantoux text. Over the 165 screened patients, 147 (89%) returned to the clinic after 3-4 days. Only 16 (10.8%) needed a phone reminder. Adherence to the screening improved remarkably compared to the previous year (89% vs 68%). A dedicated nurse and the improvement of communication may contribute to improve patients compliance. | 18,757,002 |
[Sterility in drained serums; before their use in emergency wards and in non-hospital emergency use]. | The authors detail the characteristics for the sterility of drained serums placed in a mobile emergency service unit and they determine how much time they can maintain optimum conditions for the use of these serums by means of a controlled, random, triple blind clinical test in which the units studied were serums prepared by an infusion system and a three-way valve. Data were gathered during a 12 month study period. The authors designed six operating groups based on their exposure time and where they were kept. These samples totaled 672 units. The authors carried out 12 microbiological cultural analyses for each unit; these analyses were tested for bacteria and fungi, both aerobic and anaerobic. The authors contrasted their hypothesis with a multivariable logistic regression model used as the variable for sterility A value of p < 0.05 was considered to be significant. Results were obtained on 669 serums, 98.82% of samples. Colonization was found in 1.7% of the 8028 cultures analyzed; in only 2 cases was there a register greater than 10 UFC/ml. This colonization corresponded to 103 serums which were then classified as non-sterile. For sterility the logistic regression model did not show any significant association with the various operating groups, which were controlled by means of two possible variable methods. The authors did not find evidence that recently drained serums were different, from the point of view of sterility, than the serums exposed during 24, 48 or 72 hours but, as well as for the groups, the incidences of these serums tripled the risk of colonization. The authors concluded they could use serums prepared previously and these serums sterility were guaranteed to the same degree as recently drained serums. | 18,757,014 |
Phosphorylation of yellow fever virus NS5 alters methyltransferase activity. | Serine/threonine phosphorylation of the nonstructural protein 5 (NS5) is conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. Mass spectrometry was used to characterize phosphorylated residues of yellow fever virus (YFV) NS5 expressed in mammalian cells. Multiple different phosphopeptides were detected. Mutational and additional mass spectrometry data implicated serine 56 (S56), a conserved residue near the active site in the NS5 methyltransferase domain, as one of the phosphorylation sites. Methyltransferase activity is required to form a methylated RNA cap structure and for translation of the YFV polyprotein. We show the 2'-O methylation reaction requires the hydroxyl side chain of S56, and replacement with a negative charge inhibits enzymatic activity. Furthermore mutational alteration of S56, S56A or S56D, prevents amplification in a viral replicon system. Collectively our data suggest phosphorylation of NS5 S56 may act to shut down capping in the viral life cycle. | 18,757,072 |
The Acheulean massive scrapers of Gesher Benot Ya'aqov-a product of the biface chaîne opératoire. | The presence of large scrapers has been reported from Acheulean sites worldwide but they are rarely described in detail. At Gesher Benot Ya'aqov (GBY), a similar group of artifacts, named here "massive scrapers," was identified as a significant component of the lithic assemblage. In this paper, we define and describe this Acheulean tool type and discuss its size, morphology, and technology. We demonstrate that at GBY these tools were shaped on flakes that were side-products of the reduction sequence to produce bifaces (handaxes and cleavers). We hypothesize that these blanks were rejected as potential bifaces during the knapping sequence but considered suitable for the retouching of massive scrapers, and were set aside for future work. We support our view with data from archaeological finds younger than those of GBY, as well as with evidence from controlled experimental knapping and ethnoarchaeological observations. We then discuss the contribution of this elaborate knapping strategy to our understanding of Lower Paleolithic hominin behavior, particularly in the domains of multifaceted planning and foresight. | 18,757,076 |
Children's pre-operative tonsillectomy pain education: clinical outcomes. | To examine the effects of pre-operative tonsillectomy pain education on children's (7-13 years) self-reported pre-operative anxiety and post-operative clinical outcomes (i.e., anxiety, pain intensity, quality of pain and sleep, oral intake, perceptions of pre-operative education, and pain expectation). A prospective, repeated measures, quasi-experimental design using an age appropriate pain education booklet (n = 30) and a standard care comparison group (n = 30) was employed to investigate children's pre- and post-education anxiety and post-operative tonsillectomy with or without adenoidectomy subjective experiences in the hospital and home settings. Group comparisons were performed using the Wilcoxon test, Fisher's exact test, repeated measures analysis of variance, and mixed model regression. There were no significant differences between groups for measures of anxiety, pain intensity, quality of pain and sleep, oral intake, or expected pain. There was no change in anxiety before or after pre-operative education (P = 0.85). Ninety-six percent (n = 25) of the children in the intervention group reported that pre-operative pain education helped with their post-operative pain and 72% (n = 16) in the control group stated that it would be helpful to learn about pain before surgery. The majority of children in both the intervention and control groups (96%, 91%, respectively) stated learning about the 0-10 numeric pain intensity scale helped or would be helpful to learn pre-operatively. Pre-operative pain education did not affect anxiety. Children valued pre-operative pain education. Pre-operative pain education may influence children's perceptions of medical care. | 18,757,103 |
Effective rates of heavy metal release from alkaline wastes--quantified by column outflow experiments and inverse simulations. | Column outflow experiments operated at steady state flow conditions do not allow the identification of rate limited release processes. This requires an alternative experimental methodology. In this study, the aim was to apply such a methodology in order to identify and quantify effective release rates of heavy metals from granular wastes. Column experiments were conducted with demolition waste and municipal waste incineration (MSWI) bottom ash using different flow velocities and multiple flow interruptions. The effluent was analyzed for heavy metals, DOC, electrical conductivity and pH. The breakthrough-curves were inversely modeled with a numerical code based on the advection-dispersion equation with first order mass-transfer and nonlinear interaction terms. Chromium, Copper, Nickel and Arsenic are usually released under non-equilibrium conditions. DOC might play a role as carrier for those trace metals. By inverse simulations, generally good model fits are derived. Although some parameters are correlated and some model deficiencies can be revealed, we are able to deduce physically reasonable release-mass-transfer time scales. Applying forward simulations, the parameter space with equifinal parameter sets was delineated. The results demonstrate that the presented experimental design is capable of identifying and quantifying non-equilibrium conditions. They show also that the possibility of rate limited release must not be neglected in release and transport studies involving inorganic contaminants. | 18,757,112 |
Upper limb motor strategies in persons with and without shoulder impingement syndrome across different speeds of movement. | Activities requiring repetitive arm movements, including high velocity actions, have been identified as a risk factor for shoulder impingement. However, the effect of speed on upper limb motor strategies has yet to be evaluated for individuals with shoulder impingement. The aims of this study were to characterize upper limb motor strategies in individuals with and without shoulder impingement during reaching at natural speed and to evaluate their adaptation to higher speeds of movement. Twenty healthy individuals and 33 individuals with shoulder impingement took part in one evaluation session. They performed reaching at natural and fast speeds, toward targets located at 90 degrees of arm elevation in two different planes. Reaching speed, upper limb kinematics and shoulder muscular activity were used to characterize motor strategies. Individuals with shoulder impingement present altered motor strategies during reaching tasks. However, changes with speed were comparable in both groups, showing similar adaptation to speed. Larger intergroup differences were found when individuals with shoulder impingement were separated into groups presenting higher or lower than normal clavicular elevation. In the frontal plane, increased clavicular elevation for individuals with impingement was associated with more trunk rotation, less elbow flexion and upper trapezius electromyographic activity during reaching, and a more anterior plane of shoulder elevation at the end of reaching as compared to the healthy individuals. The present results demonstrate that not all individuals with shoulder impingement present the same abnormal motor strategy. Therefore, characterizing motor strategies before implementing rehabilitation intervention is essential. | 18,757,123 |
Distribution of toxic trace elements in soil/sediment in post-Katrina New Orleans and the Louisiana Delta. | This study provided a comprehensive assessment of seven toxic trace elements (As, Pb, V, Cr, Cd, Cu, and Hg) in the soil/sediment of Katrina affected greater New Orleans region 1 month after the recession of flood water. Results indicated significant contamination of As and V and non-significant contamination of Cd, Cr, Cu, Hg and Pb at most sampling sites. Compared to the reported EPA Region 6 soil background inorganic levels, except As, the concentrations of other six elements had greatly increased throughout the studied area; St. Bernard Parish and Plaquemines Parish showed greater contamination than other regions. Comparison between pre- and post-Katrina data in similar areas, and data for surface, shallow, and deep samples indicated that the trace element distribution in post-Katrina New Orleans was not obviously attributed to the flooding. This study suggests that more detailed study of As and V contamination at identified locations is needed. | 18,757,126 |
Photocatalytic degradation of p-phenylenediamine with TiO2-coated magnetic PMMA microspheres in an aqueous solution. | This study investigates the photocatalytic degradation of p-phenylenediamine (PPD) with titanium dioxide-coated magnetic poly(methyl methacrylate) (TiO2/mPMMA) microspheres. The TiO2/mPMMA microspheres are employed as novel photocatalysts with the advantages of high photocatalytic activity, magnetic separability, and good durability. The scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and transmission electron microscopy (TEM) images of the TiO2/mPMMA microspheres are used to characterize the morphology, element content, and distribution patterns of magnetite and TiO2 nanoparticles. The BET-specific surface area and saturation magnetization of the TiO2/mPMMA microspheres are observed as 2.21 m(2)/g and 4.81 emu/g, respectively. The photocatalytic degradation of PPD are performed under various experimental conditions to examine the effects of initial PPD concentration, TiO2/mPMMA microsphere dosage, and illumination condition on the eliminations of PPD and chemical oxygen demand (COD) concentrations. Good repeatability of photocatalytic performance with the use of the TiO2/mPMMA microspheres has been demonstrated in the multi-run experiments. The photocatalytic kinetics for the reductions of PPD and COD associated with the initial PPD concentration, UV radiation intensity, and TiO2/mPMMA microsphere dosage are proposed. The relationships between the reduction percentages of COD and PPD are clearly presented. | 18,757,136 |
Heart rate features in fetal behavioural states. | Fetal behavioural states have been defined on the basis of eye movements, body movements and heart rate patterns as presented by cardiotocography (CTG). The aim of this work was to determine whether behavioural states can be distinguished on the basis of heart rate features alone using high resolution beat-to-beat fetal magnetocardiography. Five minute magnetocardiograms were recorded at a sampling rate of 1 kHz in 40 healthy fetuses (36th-41st week of gestation). In the reconstructed RR interval time series, 256-beat epochs corresponding to the behavioural states 1F, 2F and 4F were visually identified according to heart rate patterns as defined for CTG. These epochs were then quantified using mean RR interval, its standard deviation (SDNN), its root mean square of successive difference (RMSSD) and on the basis of symbolic dynamics of short 8 beat trains. Pairwise comparison between the behavioural states showed that the values of each of these measures differed significantly between the states. Quadratic discriminant analysis further revealed that mean RR interval and SDNN sufficed to classify state with a correct classification of 92%. The results suggest that measures that quantify overall aspects of heart rate can distinguish RR interval time series which were classified into different fetal behavioural states. The differences in short-term variability as quantified by RMSSD and symbolic dynamics may help reveal new aspects of these states. | 18,757,143 |
The presence of urinary nitrites is a significant predictor of pediatric urinary tract infection susceptibility to first- and third-generation cephalosporins. | Previous studies in adults have refuted the use of nitrites as a predictor of bacterial resistance to both trimethoprim-sulfamethoxazole and cephalosporins. Some centers now consider first-line outpatient therapy with an oral third-generation cephalosporin appropriate for young children. The objective of this study was to determine if nitrite-negative pediatric urinary tract infections (UTIs) were more likely than nitrite-positive UTIs to be resistant to cephalosporins. This may enable physicians to adjust antimicrobial therapy before patients leave the Emergency Department (ED) to avoid the complications of ineffectively treated pediatric UTIs. A retrospective chart review examined, over a 9-month period, 173 pediatric patients who were diagnosed with a clinical UTI in the ED and who also had a positive urine culture and a recorded dipstick at the time of visit. The chi-squared test and Fisher's exact test were used to compare nitrite-negative vs. nitrite-positive UTIs for resistance to third-generation cephalosporins and other empiric antimicrobials. For third-generation cephalosporins, 1.4% of nitrite-positive UTIs were resistant, whereas 14.4% of nitrite-negative UTIs were resistant (95% confidence interval [CI] -0.22 to -0.05). For first-generation cephalosporins, 8.4% were resistant in the nitrite-positive group, compared to 22.2% in the nitrite-negative group (95% CI -0.24 to -0.03). The absence of urinary nitrites is a significant indicator for potential resistance to cephalosporins in pediatric UTIs. Due to low levels of pediatric UTI resistance, cephalosporins continue to represent useful empiric therapy in the general pediatric population. However, in high-risk patients, physicians may opt to alter their empiric choice of antibiotic based on the presence of urinary nitrites. | 18,757,159 |
HPV testing versus repeat Pap testing for the management of a minor abnormal Pap smear: evaluation of a decision aid to support informed choice. | To examine women's informed preference for the management of a mildly abnormal Pap smear and the impact of a decision aid. Women (n=106) were given a choice of management supported by a decision aid and surveyed before, and after decision making to evaluate predictors of choice and decision aid impact. HPV triage was preferred by most women (65%) although a substantial minority selected repeat Pap testing (35%). Women who chose HPV triage were more likely to have had children, have had a previous abnormal Pap smear and were more distressed than women who chose a repeat Pap test. In total, 68% of women made an informed choice. Rapid timing of follow-up was important for women choosing HPV testing. The lower chance of colposcopy and greater opportunity for regression, were rated as important by women choosing Pap testing. Decisional conflict was lower among women who chose HPV triage. No other differences in short-term psychological outcomes were found. The decision aid supported informed choice among the majority of women. Women tailored their choice to their practical, health and psychological needs. Offering women an informed choice for a mildly abnormal Pap smear may enable women to select the management that best suits their circumstances. | 18,757,164 |
Minimal access breast surgery: a single breast incision for breast conservation surgery and sentinel lymph node biopsy. | Minimal access breast surgery (MABS) is a procedure that completes breast conservation surgery (BCS) and sentinel node biopsy (SNB) through a single incision. It allows access to axillary sentinel nodes via the breast incision and also provides access to the internal mammary nodes (IMN) as well as other nodal sites when needed. The aims of this study are to describe the MABS approach and to evaluate its safety and efficacy in cases undergoing BCS and SNB (axillary or IMN) for treatment of breast cancer. The surgical technique for MABS is described. One hundred and three consecutive clinically lymph node negative patients undergoing BCS and SNB (axillary or IMN) were considered for MABS. Cases were classified according to the location of sentinel nodes dissected (axillary, internal mammary or other), the location of the tumour and whether MABS was used. The success of MABS was calculated based on the number of cases where BCS and SNB were completed through a single breast incision. Number of lymph nodes (LN) retrieved, rate of LN positivity, aesthetics and complications were documented. Eighty-six percent of cases of BCS with axillary-only SNB were completed with MABS. For cases of BCS with axillary and IMN SNB, MABS was successful for BCS and IMN SNB in 97% of cases and for BCS and SNB from both nodal regions in 63%. There was only one case, a woman with breast prostheses, who required three separate incisions. When axillary-only SNB cases were completed with MABS, an average of 2.9 axillary LN per case with a 29% axillary LN positivity rate was seen. When axillary and IMN SNB were completed with MABS for both regions, an average of 3.0 axillary LN per case were retrieved with an axillary LN positivity rate of 65%. When separate axillary and breast incisions were made, 2.7 LN per case were removed with an axillary LN positivity rate of 30%. Aesthetics were excellent and there were no complications associated with reaching the nodes through the breast incision. MABS is a feasible option for the majority of women undergoing BCS and SNB and it does not compromise the success of SNB. | 18,757,165 |
In vivo wear rate of the Birmingham Hip Resurfacing arthroplasty. A review of 10 retrieved components. | The wear of 8 femoral and 2 acetabular components of the Birmingham Hip Resurfacing (Midland Medical Technologies Ltd, Birmingham, UK) was measured using a coordinate measuring machine (CMM5; SIP, Geneva, Switzerland). After a median in situ time of 13 months, measurements of the Birmingham Hip Resurfacing femoral heads revealed a median volumetric wear of 2.9 mm(3). In one case with a cup abduction angle of 70 degrees , a significantly higher wear of 17.8 mm(3) was found. The 2 acetabular components showed volumetric wear of 5.4 and 27.6 mm(3) after 14 and 15 months in vivo. The wear rates of the investigated femoral components were somewhat, but not significantly, higher than the previously investigated 28-mm Metasul heads (median, 0.8 mm(3); Zimmer GmbH, Winterthur, Switzerland). | 18,757,168 |
Clinical trials for children with cancer in Europe - still a long way from harmonisation: a report from SIOP Europe. | Clinical trials for children with cancer have been particularly hard hit by the introduction of the EU Clinical Trials Directive in 2004. Largely investigator-led and lacking in commercial sponsorship, they have struggled to find the resources necessary to comply with the complex bureaucracy. These rare diseases require multinational participation to permit appropriately powered clinical trials to be undertaken. Differences in interpretation of the Directive by national regulatory authorities have had a disproportionate effect on trials in children, highlighted by differences in what is deemed an 'investigational medicinal product' when paediatric use of an old drug is outside its licensed indication. Insurance costs have increased a 100-fold with no increase in actual risk between consecutive trials from the same study group. Issues raised at the recent conference held to reappraise the operation of the Directive are summarised to emphasise the particular issues for trials in children with cancer. | 18,757,192 |
Identification of equid herpesvirus-5 in respiratory liquids: a retrospective study of 785 samples taken in 2006-2007. | During a case control study undertaken in 2006-2007, a screening and consensus polymerase chain reaction (PCR) was performed to evaluate the potential role of equid herpesviruses (EHV) in several occurrences of respiratory disorders in 661 horses. Of 785 bronchoalveolar or tracheal lavage fluid samples submitted for analysis, 20 were positive for EHV-5 DNA by sequential analysis of the consensus PCR product. Nineteen of those samples were confirmed using a specific EHV-5 PCR. No particular changes in cytological profile could be associated with the detection of EHV-5 in contrast to suggestions in previous reports of natural or experimental respiratory viral infections in horses or ponies. This is the first description of EHV-5 isolation in equine respiratory fluids in Europe, but further investigations are needed to determine the potential pathogenic role of this gammaherpesvirus in the horse. | 18,757,217 |
Trastuzumab administration associated with change in HER2 status. | Recent results from large randomized clinical trials have demonstrated that administration of trastuzumab reduces the risk of death by half in patients with early-stage breast cancer; however, controversy still exists as to the timing and duration of treatment with trastuzumab in the adjuvant setting and whether its administration should be continued after recurrence of disease. We present the unusual case of a patient with HER2/neu-positive stage I breast cancer who, after receiving adjuvant trastuzumab, relapsed to develop HER2/neu-negative metastatic disease. | 18,757,266 |
Global temperature stabilization via controlled albedo enhancement of low-level maritime clouds. | An assessment is made herein of the proposal that controlled global cooling sufficient to balance global warming resulting from increasing atmospheric CO2 concentrations might be achieved by seeding low-level, extensive maritime clouds with seawater particles that act as cloud condensation nuclei, thereby activating new droplets and increasing cloud albedo (and possibly longevity). This paper focuses on scientific and meteorological aspects of the scheme. Associated technological issues are addressed in a companion paper. Analytical calculations, cloud modelling and (particularly) GCM computations suggest that, if outstanding questions are satisfactorily resolved, the controllable, globally averaged negative forcing resulting from deployment of this scheme might be sufficient to balance the positive forcing associated with a doubling of CO2 concentration. This statement is supported quantitatively by recent observational evidence from three disparate sources. We conclude that this technique could thus be adequate to hold the Earth's temperature constant for many decades. More work--especially assessments of possible meteorological and climatological ramifications--is required on several components of the scheme, which possesses the advantages that (i) it is ecologically benign--the only raw materials being wind and seawater, (ii) the degree of cooling could be controlled, and (iii) if unforeseen adverse effects occur, the system could be immediately switched off, with the forcing returning to normal within a few days (although the response would take a much longer time). | 18,757,272 |
Carbon neutral hydrocarbons. | Reducing greenhouse gas emissions from the transportation sector may be the most difficult aspect of climate change mitigation. We suggest that carbon neutral hydrocarbons (CNHCs) offer an alternative pathway for deep emission cuts that complement the use of decarbonized energy carriers. Such fuels are synthesized from atmospheric carbon dioxide (CO2) and carbon neutral hydrogen. The result is a liquid fuel compatible with the existing transportation infrastructure and therefore capable of a gradual deployment with minimum supply disruption. Capturing the atmospheric CO2 can be accomplished using biomass or industrial methods referred to as air capture. The viability of biomass fuels is strongly dependent on the environmental impacts of biomass production. Strong constraints on land use may favour the use of air capture. We conclude that CNHCs may be a viable alternative to hydrogen or conventional biofuels and warrant a comparable level of research effort and support. | 18,757,281 |
Reperfusion-associated hemorrhagic transformation in SHR rats: evidence of symptomatic parenchymal hematoma. | Symptomatic hemorrhagic transformation (HT) is the most important complicating factor after treatment with intravenous tissue plasminogen activator. In this study, we used multimodal magnetic resonance imaging to investigate the incidence and severity of reperfusion-based HT in spontaneously hypertensive rats after ischemia/reperfusion. Twenty male spontaneously hypertensive rats were subjected to 30 minutes of middle cerebral artery occlusion via the suture model. Diffusion-weighted, T(2)-weighted, and gradient-echo imaging were performed on days 1, 2, 3, 4, and 7 for longitudinal evaluation of lesion evolution, vasogenic edema, and HT, respectively. Findings on gradient-echo images were classified according to the severity of hemorrhage: no HT; punctate or small petechial hemorrhage (HI-1); confluent petechial hemorrhage (HI-2); hematoma with absent/mild space-occupying effect (PH-1, <or=30% lesion volume); and hematoma with significant space-occupying effect and potential perihematomal edema (PH-2, >30% lesion volume). Histopathologic evaluation of HT was performed after final imaging for comparison with magnetic resonance imaging results. Final hemorrhage scores based on severity were as follows: HI-1 23.1%, HI-2 30.8%, PH-1 30.8%, and PH-2 15.4%. Similar to clinical observations, only PH-2 was associated with neurologic deterioration and associated weight loss. This model has a high incidence of parenchymal hematomas (46.2%) and therefore is appropriate for the evaluation of novel therapeutics targeting blood-brain barrier integrity and the reduction of symptomatic HT events (PH-2), as well as those potentially "at risk" for neurologic deterioration (PH-1). | 18,757,286 |
Resident cellular components of the lung: developmental aspects. | In a recent workshop organized by the NIH-NHLBI, investigators working on different aspects of lung biology met to discuss recent progress regarding the origin, development, and characterization of the various cell lineages present in the lung in both normal and disease states. The workshop was entitled "Resident Cellular Components of the Human Lung: Current Knowledge and Goals for Research on Cell Phenotyping and Function." In this article we will highlight some of the developmental aspects of the lung discussed at the meeting. We will review information about developmental signals that are possibly reactivated during lung regeneration/repair and disease processes, and we will pose the questions and challenges viewed to be relevant to further advance the field. | 18,757,315 |
Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis. | Substantial evidence implicates insulin-like growth factor-I (IGF-I) signaling in the development and progression of breast cancer. To more clearly elucidate the role of IGF in human breast cancer, we identified and then examined gene expression patterns of IGF-I-treated breast cancer cells. MCF-7 cells were stimulated with IGF-I for 3 or 24 hours and were profiled for greater than 22,000 RNA transcripts. We defined an IGF-I signature pattern of more than 800 genes that were up- or downregulated at both time points. The gene signature was examined in clinical breast tumors and in experimental models that represented other oncogenic pathways. The signature was correlated with clinical and pathologic variables and with patient outcome. IGF-I caused temporal changes in gene expression that were strongly associated with cell proliferation, metabolism, and DNA repair. Genes with early and sustained regulation by IGF-I were highly enriched for transcriptional targets of the estrogen receptor (ER), Ras/extracellular signal-related kinase 1/2, and phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathways. In three large, independent data sets of profiled human breast tumors, the IGF-I signature was manifested in the majority of ER-negative breast tumors and in a subset (approximately 25%) of ER-positive breast tumors. Patients who had tumors that manifested the IGF-I signature (including patients who did not receive adjuvant therapy) had a shorter time to a poor outcome event. The IGF gene signature was highly correlated with numerous poor prognostic factors and was one of the strongest indicators of disease outcome. Transcriptional targets of IGF-I represent pathways of increased aggressiveness and possibly hormone independence in clinical breast cancers. | 18,757,322 |
Pharmacodynamic-guided modified continuous reassessment method-based, dose-finding study of rapamycin in adult patients with solid tumors. | Pharmacodynamic studies are frequently incorporated into phase I trials, but it is uncommon that they guide dose selection. We conducted a dose selection study with daily rapamycin (sirolimus) in patients with solid tumors employing a modified continuous reassessment method (mCRM) using real-time pharmacodynamic data as primary dose-estimation parameter. We adapted the mCRM logit function from its classic toxicity-based input data to a pharmacodynamic-based input. The pharmacodynamic end point was skin phospho-P70 change after 28 days. Pharmacodynamic effect was defined as at least 80% inhibition from baseline. The first two dose levels (2 and 3 mg) were evaluated before implementing the mCRM, and the data used to estimate the next dose level based on statistical modeling. Toxicity-based boundaries limited the escalation steps. Other correlates analyzed were positron emission tomography (PET) and computed tomography, pharmacokinetics, phospho-P70 in peripheral-blood mononuclear cells, and tumor biopsies in patients at the maximum-tolerated dose (MTD). Twenty-one patients were enrolled at doses between 2 and 9 mg. Pharmacodynamic effect occurred across dose levels, and toxicity boundaries ultimately drove dose selection. The MTD of daily oral rapamycin was 6 mg. Toxicities in at least 20% were hyperglycemia, hyperlipidemia, elevated transaminases, anemia, leucopenia, neutropenia, and mucositis. Pharmacokinetics were consistent with prior data, and exposure increased with dose. No objective responses occurred, but five previously progressing patients received at least 12 cycles. PET showed generalized stable or decreased glucose uptake unrelated to antitumor effect. mCRM-based dose escalation using real-time pharmacodynamic assessment was feasible. However, the selected pharmacodynamic end point did not correlate with dose. Toxicity ultimately drove dose selection. Rapamycin is a well-tolerated and active oral anticancer agent. | 18,757,332 |
LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase. | Intracellular signals elicited by LDLs are likely to play a role in the pathogenesis associated with increased LDL blood levels. We have previously determined that LDL stimulation of human skin fibroblasts, used as a model system for adventitial fibroblasts, activates p38 mitogen-activated protein kinases (MAPKs), followed by IL-8 production and increased wound-healing capacity of the cells. The proximal events triggering these responses had not been characterized, however. Here we show that MAPK kinases MKK3 and MKK6, but not MKK4, are the upstream kinases responsible for the activation of the p38 MAPKs and stimulation of wound closure in response to LDLs. Phosphoinositide 3 kinases (PI3Ks) and Ras have been suggested to participate in lipoprotein-induced MAPK activation. However, specific PI3K inhibitors or expression of a dominant-negative form of Ras failed to blunt LDL-induced p38 MAPK activation. The classical LDL receptor does not participate in LDL signaling, but the contribution of other candidate lipoprotein receptors has not been investigated. Using cells derived from scavenger receptor class B type I (SR-BI) knockout mice or the BLT-1 SR-BI inhibitor, we now show that this receptor is required for LDLs to stimulate p38 MAPKs and to promote wound healing. Identification of MKK3/6 and SR-BI as cellular relays in LDL-mediated p38 activation further defines the signaling events that could participate in LDL-mediated pathophysiological responses. | 18,757,346 |
Health promotion of faculty and staff: the school nurse's role. | Health promotion of school faculty and staff is an important part of a coordinated school health program. The lack of evaluation of health promotion programs and inconsistent results highlighting the efficacy and benefits of programs adds to employers' perceptions of inconsistent benefits. More studies evaluating effectiveness and development of standards for health promotion programs must be conducted. The steps essential to a successful health promotion program are assessment of the target population's needs, planning, implementation, and evaluation of the health promotion program. School nurses are one of many groups who must be involved in the development of health promotion programs for school faculty and staff. Collaboration with other school personnel, administration, and community resources is essential to the success of a health promotion program. | 18,757,350 |
Biomesh placement in laparoscopic repair of paraesophageal hernias. | The placement of mesh in the crural closure of paraesophageal hiatal hernia repairs has been shown to decrease hernia recurrence rates. Typical synthetic mesh are easy to use but have high rate of erosion into the esophagus. Alternatively, biologic mesh decrease the risk of erosion, but are more difficult to manipulate, and there is currently no well-described method for securing them. Current fixation techniques of mesh are difficult, cumbersome, incur extra expense, and are not without complications. A method that requires no additional sutures or staples and achieves excellent contact and reinforcement of the crural closure is presented. | 18,757,377 |
Is operative conversion necessary for patients diagnosed with dense adhesions during an elective laparoscopic colectomy? | Laparoscopic colectomy is often complicated by adhesions. Studies examining the morbidity of laparoscopic lysis of adhesions (LOA) combined with colectomy are sparse. The goal of this study was to prospectively evaluate the results of using the harmonic scalpel to lyse adhesions in patients undergoing laparoscopic colectomy. Laparoscopic colectomy was performed in 83 patients between November 2003 and April 2007. A total of 20 patients underwent laparoscopic colectomy with LOA and 53 patients underwent laparoscopic colectomy alone. Patients were prospectively followed to determine operative time (OT), blood loss, operative conversion, length of stay (LOS), and 30-day morbidity. Operative conversion was 2%, mean estimated blood loss (EBL) was 95+/-84 mL, and mean OT was 220+/-64 minutes. There were no anastomotic leaks or perioperative mortalities. There were 9 major complications (11%). Patients undergoing laparoscopic colectomy with LOA (n=20) compared with patients undergoing laparoscopic colectomy alone (n=63) had similar conversion rates (5% vs 2%), EBL (115+/-108 vs 88+/-74 mL), and major complications (15% vs 10%), but prolonged minor complications (25% vs 6%) and LOS (6.0+/-3.0 vs 4.6+/-1.5 days). Laparoscopic LOA combined with colectomy leads to similar conversion rates and major morbidity compared to laparoscopic colectomy alone. | 18,757,381 |
Basal cell carcinoma is not granulation tissue in the venous leg ulcer. | The authors present a case of a 76-year-old female with a 7-year history of a nonhealing leg ulcer. The wound surface had epithelial tissue present in a diffuse way with shiny granulations on parts of the edge of the ulcer. A biopsy of the ulcer edge was performed to study the reasons for the absence of response to treatment and the presence of abnormal granulation tissue. The result showed the presence of a basal cell carcinoma. The authors conclude that skin biopsy is very important in nonhealing chronic venous ulcers because carcinomas may mimic granulation tissue and complicate venous ulcers. | 18,757,394 |
Synergistic inhibition with a dual epidermal growth factor receptor/HER-2/neu tyrosine kinase inhibitor and a disintegrin and metalloprotease inhibitor. | The ErbB family of receptors is overexpressed in numerous human tumors. Overexpression correlates with poor prognosis and resistance to therapy. Use of ErbB-specific antibodies to the receptors (Herceptin or Erbitux) or ErbB-specific small-molecule inhibitors of the receptor tyrosine kinase activity (Iressa or Tarceva) has shown clinical efficacy in several solid tumors. An alternative method of affecting ErbB-initiated tumor growth and survival is to block sheddase activity. Sheddase activity is responsible for cleavage of multiple ErbB ligands and receptors, a necessary step in availability of the soluble, active form of the ligand and a constitutively activated ligand-independent receptor. This sheddase activity is attributed to the ADAM (a disintegrin and metalloprotease) family of proteins. ADAM 10 is the main sheddase of epidermal growth factor (EGF) and HER-2/neu cleavage, whereas ADAM17 is required for cleavage of additional EGF receptor (EGFR) ligands (transforming growth factor-alpha, amphiregulin, heregulin, heparin binding EGF-like ligand). This study has shown that addition of INCB3619, a potent inhibitor of ADAM10 and ADAM17, reduces in vitro HER-2/neu and amphiregulin shedding, confirming that it interferes with both HER-2/neu and EGFR ligand cleavage. Combining INCB3619 with a lapatinib-like dual inhibitor of EGFR and HER-2/neu kinases resulted in synergistic growth inhibition in MCF-7 and HER-2/neu-transfected MCF-7 human breast cancer cells. Combining the INCB7839 second-generation sheddase inhibitor with lapatinib prevented the growth of HER-2/neu-positive BT474-SC1 human breast cancer xenografts in vivo. These results suggest that there may be an additional clinical benefit of combining agents that target the ErbB pathways at multiple points. | 18,757,423 |
Chondroitin sulfate E fragments enhance CD44 cleavage and CD44-dependent motility in tumor cells. | During tumor cell invasion, certain extracellular matrix (ECM) components such as hyaluronan (HA) are degraded into small oligosaccharides, which are detected in patients. We previously reported that such HA oligosaccharides induce the proteolytic cleavage of an ECM-binding molecule CD44 from tumor cells and promote tumor cell migration in a CD44-dependent manner. Here, we report that chondroitin sulfate E (CSE), another component of the tumor ECM, strongly enhances CD44 cleavage and tumor cell motility when degraded into oligosaccharides. CSE and its degradation products were detected in pancreatic ductal adenocarcinoma. In CD44-expressing pancreatic tumor cells, degraded forms of CSE but not intact CSE enhanced CD44 cleavage; enzymatic digestion of such low-molecular weight CSE (LMW-CSE) abrogated this enhancement. Among the LMW-CSE preparations examined, 3-kDa CSE most potently induced CD44 cleavage. Nuclear magnetic resonance analysis showed that the 3-kDa-CSE bound to CD44, and that blocking such binding abrogated the CD44 cleavage induction. LMW-CSE also induced prominent filopodia formation and cytoskeletal changes in tumor cells; these effects were also abrogated by blocking the LMW-CSE binding to CD44. Chemically synthesized CSE hexasaccharides also enhanced the CD44 cleavage and tumor cell motility in a CD44-dependent manner. We conclude that the degraded forms of CSE modulate cell adhesion and migration by interacting with tumor-cell CD44, suggesting that the degradation products of tumor-associated ECMs that interact with CD44 play a significant role in CD44-mediated tumor progression. | 18,757,435 |
Intraindividual comparative study of corneal and ocular wavefront aberrations after biaxial microincision versus coaxial small-incision cataract surgery. | To compare the optical outcomes of biaxial microincision cataract surgery (B-MICS) versus coaxial small-incision cataract surgery (C-SICS). Thirty patients (sixty eyes) with bilateral age-related cataract underwent B-MICS through a 1.7 mm clear corneal incision (CCI) in one eye and C-SICS through a 2.8-mm CCI in the other eye. Every eye was implanted with a micro-incision aspheric aberration-free intraocular lens (Akreos MI60 AO). Preoperative corneal aberrations, and 3-month postoperative corneal and total ocular aberrations were calculated and compared. The 3-month postoperative corneal root mean square (RMS) of third- to sixth-order aberrations (p<0.001), third-order trefoil (p = 0.001), trefoil-like (p<0.001), and third-order RMS (p<0.001) were lower in the B-MICS group than in the C-SICS group. Surgically induced corneal trefoil was reduced in B-MICS eyes (p = 0.001). The total ocular high-order RMS (p = 0.002), third-trefoil (p<0.001), trefoil-like (p<0.001) and fifth-order RMS (p<0.001) were lower in B-MICS than in C-SICS eyes. Corneal aberrations were positively correlated with ocular aberrations for the RMS of third- to sixth-order aberrations, third-trefoil and spherical-like aberrations. Visual acuity, refraction and corneal astigmatism were not different between both groups. Compared with conventional surgery, B-MICS could improve the optical performances of the pseudophakic eye reducing surgically induced corneal higher-order aberrations. | 18,757,472 |
Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. | Mast cells are found in the heart and contribute to reperfusion injury following myocardial ischemia. Since the activation of A2A adenosine receptors (A2AARs) inhibits reperfusion injury, we hypothesized that ATL146e (a selective A2AAR agonist) might protect hearts in part by reducing cardiac mast cell degranulation. Hearts were isolated from five groups of congenic mice: A2AAR+/+ mice, A2AAR(-/-) mice, mast cell-deficient (Kit(W-sh/W-sh)) mice, and chimeric mice prepared by transplanting bone marrow from A2AAR(-/-) or A2AAR+/+ mice to radiation-ablated A2AAR+/+ mice. Six weeks after bone marrow transplantation, cardiac mast cells were repopulated with >90% donor cells. In isolated, perfused hearts subjected to ischemia-reperfusion injury, ATL146e or CGS-21680 (100 nmol/l) decreased infarct size (IS; percent area at risk) from 38 +/- 2% to 24 +/- 2% and 22 +/- 2% in ATL146e- and CGS-21680-treated hearts, respectively (P < 0.05) and significantly reduced mast cell degranulation, measured as tryptase release into reperfusion buffer. These changes were absent in A2AAR(-/-) hearts and in hearts from chimeric mice with A2AAR(-/-) bone marrow. Vehicle-treated Kit(W-sh/W-sh) mice had lower IS (11 +/- 3%) than WT mice, and ATL146e had no significant protective effect (16 +/- 3%). These data suggest that in ex vivo, buffer-perfused hearts, mast cell degranulation contributes to ischemia-reperfusion injury. In addition, our data suggest that A2AAR activation is cardioprotective in the isolated heart, at least in part by attenuating resident mast cell degranulation. | 18,757,481 |
Soluble guanylyl cyclase activation by HMR-1766 (ataciguat) in cells exposed to oxidative stress. | Many vascular diseases are characterized by increased levels of ROS that destroy the biological activity of nitric oxide and limit cGMP formation. In the present study, we investigated the cGMP-forming ability of HMR-1766 in cells exposed to oxidative stress. Pretreatment of smooth muscle cells with H(2)O(2) reduced cGMP production stimulated by sodium nitroprusside (SNP) or BAY 41-2272. However, pretreatment with H(2)O(2) significantly increased HMR-1766 responses. Similar results were obtained with SIN-1, menadione, and rotenone. In addition, HMR-1766 was more effective in stimulating heme-free sGC compared with the wild-type enzyme. Interestingly, in cells expressing heme-free sGC, H(2)O(2) inhibited instead of potentiated HMR-1766 responses, suggesting that the ROS-induced enhancement of cGMP formation was heme dependent. Moreover, using truncated forms of sGC, we observed that the NH(2)-terminus of the beta(1)-subunit is required for the action of HMR-1766. Finally, to study tolerance development to HMR-1766, cells were pretreated with this sGC activator and reexposed to HMR-1766 or SNP. Results from these experiments demonstrated lack of tolerance development to HMR-1766 as well as lack of cross-tolerance with SNP. We conclude that HMR-1766 is an improved sGC activator as it has the ability to activate oxidized/heme-free sGC and is resistant to the development of tolerance; these observations make HMR-1766 a promising agent for treating diseases associated with increased vascular tone combined with enhanced ROS production. | 18,757,489 |
The paramutated SULFUREA locus of tomato is involved in auxin biosynthesis. | The tomato (Solanum lycopersicum) sulfurea mutation displays trans-inactivation of wild-type alleles in heterozygous plants, a phenomenon referred to as paramutation. Homozygous mutant plants and paramutated leaf tissue of heterozygous plants show a pigment-deficient phenotype. The molecular basis of this phenotype and the function of the SULFUREA gene (SULF) are unknown. Here, a comprehensive physiological analysis of the sulfurea mutant is reported which suggests a molecular function for the SULFUREA locus. It is found that the sulf mutant is auxin-deficient and that the pigment-deficient phenotype is likely to represent only a secondary consequence of the auxin deficiency. This is most strongly supported by the isolation of a suppressor mutant which shows an auxin overaccumulation phenotype and contains elevated levels of indole-3-acetic acid (IAA). Several lines of evidence point to a role of the SULF gene in tryptophan-independent auxin biosynthesis, a pathway whose biochemistry and enzymology is still completely unknown. Thus, the sulfurea mutant may provide a promising entry point into elucidating the tryptophan-independent pathway of IAA synthesis. | 18,757,490 |
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