pubid
int64 113k
29.1M
| question
stringlengths 10
664
| context
stringlengths 14
5.66k
| long_answer
stringlengths 1
3.03k
|
|---|---|---|---|
21,723,687 |
Does adeno-associated virus serotype 9-mediated overexpression of extracellular superoxide dismutase improve recovery from surgical hind-limb ischemia in BALB/c mice?
|
Neovascularization is a physiologic repair process that partly depends on nitric oxide. Extracellular superoxide dismutase (EcSOD) is the major scavenger of superoxide. It is an important regulator of nitric oxide bioavailability and thus protects against vascular dysfunction. We hypothesized that overexpression of EcSOD in skeletal muscle would improve recovery from hind-limb ischemia. Adeno-associated virus serotype 9 (AAV9) vectors expressing EcSOD or luciferase (control) from the cytomegalovirus promoter were cross-packaged into AAV9 capsids and injected intramuscularly into the hind-limb muscles (1 × 10(11) viral genomes/limb) of 12-week-old mice. Ischemia was induced after intramuscular injections. Laser Doppler was used to measure limb perfusion on days 0, 7, and 14 after injection. Values were expressed as a ratio relative to the nonischemic limb. EcSOD expression was measured by Western blotting. Capillary density was documented by immunohistochemical staining for platelet endothelial cell adhesion molecule. Apoptosis was assessed by terminal deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end labeling and necrosis was visually evaluated daily. EcSOD expression was twofold upregulated in EcSOD treated vs control ischemic muscles at day 14. Capillary density (capillaries/fiber) was 1.9-fold higher in treated (1.65 ± 0.02) vs control muscle (0.78 ± 0.17, P < .05). Recovery of perfusion ratio at day 14 after ischemia was 1.5-fold greater in EcSOD vs control mice (P < .05). The percentage of apoptotic nuclei was 1.3% ± 0.4% in EcSOD-treated mice compared with 4.2% ± 0.2% in controls (P < .001). Limb necrosis was also significantly lower in EcSOD vs control mice.
|
AAV9-mediated overexpression of EcSOD in skeletal muscle significantly improves recovery from hind-limb ischemia in mice, consistent with improved capillary density and perfusion ratios in treated mice.
|
21,047,394 |
Is conservation of shh cis-regulatory architecture of the coelacanth consistent with its ancestral phylogenetic position?
|
The modern coelacanth (Latimeria) is the extant taxon of a basal sarcopterygian lineage and sister group to tetrapods. Apart from certain apomorphic traits, its morphology is characterized by a high degree of retention of ancestral vertebrate structures and little morphological change. An insight into the molecular evolution that may explain the unchanged character of Latimeria morphology requires the analysis of the expression patterns of developmental regulator genes and their cis-regulatory modules (CRMs). We describe the comparative and functional analysis of the sonic hedgehog (shh) genomic region of Latimeria menadoensis. Several putative enhancers in the Latimeria shh locus have been identified by comparisons to sarcopterygian and actinopterygian extant species. Specific sequence conservation with all known actinopterygian enhancer elements has been detected. However, these elements are selectively missing in more recently diverged actinopterygian and sarcopterygian species. The functionality of the putative Latimeria enhancers was confirmed by reporter gene expression analysis in transient transgenic zebrafish and chick embryos.
|
Latimeria shh CRMs represent the ancestral set of enhancers that have emerged before the split of lobe-finned and ray-finned fishes. In contrast to lineage-specific losses and differentiations in more derived lineages, Latimeria shh enhancers reveal low levels of sequence diversification. High overall sequence conservation of shh conserved noncoding elements (CNE) is consistent with the general trend of high levels of conservation of noncoding DNA in the slowly evolving Latimeria genome.
|
12,537,557 |
Do membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain?
|
Membrane-associated progesterone receptors (MAPRs) are thought to mediate a number of rapid cellular effects not involving changes in gene expression. They do not show sequence similarity to any of the classical steroid receptors. We were interested in identifying distant homologs of MAPR better to understand their biological roles. We have identified MAPRs as distant homologs of cytochrome b5. We have also found regions homologous to cytochrome b5 in the mammalian HERC2 ubiquitin transferase proteins and a number of fungal chitin synthases.
|
In view of these findings, we propose that the heme-binding cytochrome b5 domain served as a template for the evolution of membrane-associated binding pockets for non-heme ligands.
|
14,992,117 |
Laser cordectomy without hospitalization. Is it a safe intervention?
|
To evaluate the safety of the CO2 Laser Cordectomy in the treatment of glottic carcinoma as a day-case procedure. Retrospective study of a cohort of 30 patients with glottic carcinoma treated with CO2 Laser Cordectomy at our institution between 1999-2001 as a day-case procedure. There were no major complications and no patients required re-intubation. 90% of the patients were discharged the same day of the procedure. There were three unplanned admissions to the hospital but none of them were, in our opinion, the direct result of Cordectomy. These patients were discharged the next day. 100% of the patients answered that they would repeat the experience.
|
CO2 Laser Cordectomy of the glottic carcinoma can be safely performed as an outpatient procedure if patients are selected according to specific day-case criteria.
|
8,998,144 |
Does fasting improve discrimination of grade 1 and atypical or malignant meningioma in FDG-PET?
|
We investigated the use of PET with 2[18F]fluoro-2-deoxy-D-glucose (FDG) to discriminate between atypical or malignant and grade 1 meningiomas. The influence of fasting state and high-dose corticosteroid medication was analyzed retrospectively. Preoperative PET scans of 75 patients with suspected diagnosis of intracranial meningioma were evaluated using standardized uptake values (SUV) and tumor-to-contralateral gray matter ratios (TGR) of FDG uptake. Fifty-one of 75 patients fasted before the PET scan, and 27 of 75 patients were studied under high-dose corticosteroid medication. Eighteen tumors had recurred. PET results were compared to histopathological grading. PET correctly identified 8/9 atypical or malignant meningiomas and 58/66 grade 1 meningiomas using TGR and a threshold of 1.05 in primary meningioma and 0.85 in tumor recurrence. This corresponds to a specificity of 0.88 for the detection of higher tumor grading. Specificity was significantly higher in fasting compared to nonfasting subjects (0.96 versus 0.73; p < 0.025). SUV quantification lead to a reduced specificity of 0.77 at the same level of sensitivity. The only false-negative PET finding occurred in a recurrent meningioma, which had been operated on four times before.
|
Overnight fasting before injection is needed to improve the diagnostic accuracy of FDG-PET for noninvasive metabolic grading of meningioma. Hyperglycemia in nonfasting patients and in diabetic patients may lead to overestimation of meningioma grading.
|
21,790,478 |
Does beta-blockade prevent hematopoietic progenitor cell suppression after hemorrhagic shock?
|
Severe injury is accompanied by sympathetic stimulation that induces bone marrow (BM) dysfunction by both suppression of hematopoietic progenitor cell (HPC) growth and loss of cells via HPC mobilization to the peripheral circulation and sites of injury. Previous work demonstrated that beta-blockade (BB) given prior to tissue injury both reduces HPC mobilization and restores HPC colony growth within the BM. This study examined the effect and timing of BB on BM function in a hemorrhagic shock (HS) model. Male Sprague-Dawley rats underwent HS via blood withdrawal, maintaining the mean arterial blood pressure at 30-40 mm Hg for 45 min, after which the extracted blood was reinfused. Propranolol (10 mg/kg) was given either prior to or immediately after HS. Blood pressure, heart rate, BM cellularity, and death were recorded. Bone marrow HPC growth was assessed by counting colony-forming unit-granulocyte-, erythrocyte-, monocyte-, megakaryocyte (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E) cells. Administration of BB prior to injury restored HPC growth to that of naïve animals (CFU-GEMM 59 ± 11 vs. 61 ± 4, BFU-E 68 ± 9 vs. 73 ± 3, and CFU-E 81 ± 35 vs. 78 ± 14 colonies/plate). Beta-blockade given after HS increased the growth of CFU-GEMM, BFU-E, and CFU-E significantly and improved BM cellularity compared with HS alone. The mortality rate was not increased in the groups receiving BB.
|
Administration of propranolol either prior to injury or immediately after resuscitation significantly reduced post-shock BM suppression. After HS, BB may improve BM cellularity by decreasing HPC mobilization. Therefore, the early use of BB post-injury may play an important role in attenuating the BM dysfunction accompanying HS.
|
25,598,809 |
Do a CBCT Assessment of Apical Transportation in Root Canals Prepared with Hand K-Flexofile and K3 Rotary Instruments?
|
Apical transportation changes the physical shape and physiologic environment of the root canal terminus. The aim of the present experimental study was to determine the extent of apical transportation after instrumentation with hand K-Flexofile and K3 rotary instruments by means of cone-beam computed tomography (CBCT). Forty mesiobuccal root canals of maxillary first molars, with 19-22 mm length and 20-40(°) canal curvature, were selected and assigned into two preparation groups. The first group was prepared with K-Flexofile with passive step-back technique and the second group was prepared with K3 rotary instruments. Pre and post instrumentation CBCT images were taken under similar conditions. The amount of root canal transportation was evaluated by Mann-Whitney U test and the chi-square test was used for the qualitative evaluation. The amounts of apical canal transportation with the K3 and K-Flexofile instruments were 0.105±0.088 and 0.150±0.127 mm, respectively with no statistically significant differences. In the manual technique, 25% of the canals had no apical transportation; while 30% of the canals in the K3 group were transportation free.
|
Both systems were able to preserve the initial curvature of the canals and both had sufficient accuracy. Preparation with K3 rotary instruments resulted in apical transportation similar to that of K-Flexofile.
|
26,727,713 |
Does pulsed corticosteroid treatment in MS patients stabilize disease activity following natalizumab withdrawal prior to switching to fingolimod?
|
Interruption of natalizumab (NTM) treatment in multiple sclerosis (MS) patients may be followed by disease reactivation. On the other hand, patients with positive John Cunningham virus (JCV) antibodies treated with NTM over 24 months demonstrate a higher risk for developing progressive multifocal encephalopathy (PML). No established therapeutic approach is available for treating these patients to prevent disease reactivation. Of the MS patients treated with NTM at the authors' institution, 30 were found positive for JCV abs. NTM was interrupted followed by a washout period of 6 months. During this period, 20/30 patients received monthly intravenous (i.v.) methylprednisolone (MPD) 1000 mg infusion and regular clinical assessment. On months 3 and 6, brain MRI was performed and 1000 mg MPD was administered for 5 days. All patients were clinically and radiologically stable at the time of NTM break. No clinical relapse was observed during the six-month washout period for the MS patients under monthly MPD treatment, while one patient had a relapse and active lesions in the MRI on month 6. Of the other patients not receiving i.v. MPD regularly after NTM withdrawal, one showed several active lesions in brain MRI and the other had a severe relapse.
|
Despite the limited size of this patients' cohort, the results of this study support that monthly MPD treatment for 6 months may result in a clinically stable disease status, thus ensuring safe transition to another second-line therapy such as fingolimod, following NTM withdrawal.
|
26,452,387 |
Should consent forms used in clinical trials be translated into the local dialects?
|
Obtaining informed consent is part of the expression of the principle of participant autonomy during clinical trials. It is critical that participants understand the content of informed consent forms and remain in a position to seek independent advice on its content. We conducted a survey among past participants of a clinical trial in the Kassena-Nankana Districts of rural northern Ghana about the usefulness of informed consent forms that are written in the local dialects. The written forms of local dialects are largely undeveloped. We contacted a randomly selected sample of caregivers whose children were enrolled in a completed clinical trial and interviewed them using a structured questionnaire. Analysis sought to determine participants' preference and whether or not they were likely to find confidants who will be able to read, understand and give advice on the content of the informed consent form to them when they take the informed consent forms home. We interviewed 394 caregivers, 88.6% of whom were women. About half (54%) of the respondents wanted the informed consent forms to be in the English language. Caregivers with higher than primary level education were more likely to prefer the informed consent form to be in English than those with no formal education (74% versus 26%, p = 0.04). The majority (85%) indicated that they would be able to find close confidants who would be able to read and explain it to them if it is in English. In contrast, only 8% thought they would be able to do the same if the informed consent form was written in the local language. Respondents were more likely to find close confidants to read and explain the informed consent form if it were written in English than if it were written in the local language (94% versus 19%, p value < 0.01).
|
The practice of translating informed consent forms into undeveloped local dialects and giving such copies to trial participants to send home needs to be re-evaluated. In populations where the written forms of local dialects are undeveloped and literacy is low, the use of local dialect versions of informed consent forms could ironically enhance the vulnerability of trial participants.
|
15,656,906 |
Does mDM2 negatively regulate the human telomerase RNA gene promoter?
|
We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR) promoter and play a central role in its regulation. We have also shown that pRB activates the hTR promoter, but the mechanism of pRb directed activation is unknown. It has recently been reported that pRB induces Sp1 activity by relieving inhibition mediated by mdm2. The aim was to investigate possible roles for mdm2 in hTR promoter regulation. Chromatin immunoprecipitation was used to determine binding of mdm2 to the hTR promoter. Transfection and luciferase assays were used to investigate mdm2 repression of the promoter activity and interaction with known transcriptional modulators. Here we show using chromatin immunoprecipitation that mdm2 specifically binds the hTR promoter in vivo. Transient co-transfection experiments using an hTR promoter luciferase reporter construct show that hTR promoter activity is inhibited by over-expression of mdm2 in 5637 bladder carcinoma cells (p53 and pRB negative, low mdm2). Titration of mdm2 was able to antagonise activation of hTR promoter activity mediated by pRB or Sp1 over-expression, although in the presence of pRB, mdm2 could not repress promoter activity below basal levels. Using an Sp1 binding site mutation construct we showed that mdm2 repression did not absolutely require Sp1 binding sites in the hTR promoter, suggesting the possibility of pRB/Sp1 independent mechanisms of repression. Finally, we show that NF-Y mediated transactivation of the hTR promoter was also suppressed by mdm2 in a dose-dependent manner.
|
These studies suggest that mdm2 may inhibit the hTR promoter by multiple mechanisms. Mdm2 may directly repress activation by both pRB and Sp1, or activation by NF-Y. Furthermore, the ability of mdm2 to interact and interfere with components of the general transcription machinery might partly explain the general repressive effect seen here. Elucidation of new regulators affecting hTR basal promoter activity in cancer cells provides a basis for future studies aimed at improving our understanding of the differential hTR expression between normal and cancer cells.
|
20,715,661 |
Does diagnostic value of processing cytologic aspirates of renal tumors in agar cell ( tissue ) block?
|
To adapt a method enabling utilization of most of the harvest from a fine needle aspirate in an effort to improve diagnostic accuracy in the assessment of a renal tumor in a single histologic slide. In a series of 43 renal tumors, 2 fine needle aspirations were performed, 4 smears were prepared after each aspiration for conventional cytology and the remaining aspirate was processed for the improved agar microbiopsy (AM) method. Conventional cytology slides, AM slides and surgical specimens were diagnosed separately, after which the diagnoses were compared. Immunohistochemistry was performed as required on the AM sections. Surgical specimens served as the gold standard. In 53% of conventional cytologic smears, the cellular yield was sufficient to render a correct diagnosis. In 12% the diagnosis was incorrect, in 21% only a differential diagnosis could be formulated, and in 14% too few diagnostic cells were present in the conventional smears for a cytologic diagnosis. It was, however, possible to correctly diagnose histologic sections from 97% of AM tissue blocks. In 11 cases this was facilitated with immunohistochemistry. In only 1 case did the AM tissue block contain too few cells to formulate a diagnosis; the conventional cytologic sample in this case contained enough diagnostic cells. In all cases the AM diagnosis was confirmed in the definitive surgical specimen.
|
Our AM technique for processing fine needle aspirates from renal tumors results in a major enhancement of diagnostic accuracy of such aspirates and should be valuable in the preoperative diagnosis of large, as well as small, renal tumors.
|
23,107,582 |
Does optimization of intraocular lens constant improve refractive outcomes in combined endothelial keratoplasty and cataract surgery?
|
To evaluate the accuracy of intraocular lens (IOL) power calculations with A-constant optimization in Descemet's stripping automated endothelial keratoplasty (DSAEK) combined with cataract extraction and intraocular lens implantation (DSAEK triple procedure). Retrospective case series. Thirty eyes of 22 patients with Fuchs' endothelial dystrophy who underwent the DSAEK triple procedure performed by a single surgeon. Prediction errors were calculated retrospectively for consecutive DSAEK triple procedures. These prediction errors then were used to determine an IOL constant for this cohort of patients. The new optimized IOL constant subsequently was compared with the manufacturer's IOL constant, allowing evaluation and quantification of refractive benefits of optimization. The error in diopters (D) of the predicted refraction with the manufacturer's and optimized IOL constants. Optimization of the A constant decreased the mean absolute error (MAE) from 1.09 ± 0.63 D (range, 0.12-2.41 D) to 0.61 ± 0.4 D (range, 0-1.58 D; P = 0.004). Comparing the intended and final postoperative refractions calculated with the original manufacturer's constant and the optimized constant, 20% versus 43% of all eyes were in the less than 0.5-D range and 50% versus 83% of all eyes were in the less than 1.0-D range of the target refraction. Furthermore, optimization decreased the number of eyes that were more than 1.0 D from the target refraction from 50% to 17%.
|
Optimization of the IOL constant showed significantly improved accuracy of predicted postoperative refraction compared with the manufacturer's IOL constant, which may help improve the postoperative refractive outcomes in patients undergoing the DSAEK triple procedure.
|
26,546,411 |
Is p21 deficiency susceptible to osteoarthritis through STAT3 phosphorylation?
|
Osteoarthritis (OA) is a multifactorial disease, and recent studies have suggested that cell cycle-related proteins play a role in OA pathology. p21 was initially identified as a potent inhibitor of cell cycle progression. However, it has been proposed that p21 is a regulator of transcription factor activity. In this study, we evaluated the role of p21 in response to biomechanical stress. Human chondrocytes were treated with p21-specific small interfering RNA (siRNA), and cyclic tensile strain was introduced in the presence or absence of a signal transducer and activator of transcription 3 (STAT3)-specific inhibitor. Further, we developed an in vivo OA model in a p21-knockout background for in vivo experiments. The expression of matrix metalloproteinase (MMP13) mRNA increased in response to cyclic tensile strain following transfection with p21 siRNA, whereas the expression of aggrecan was decreased. Phospho-STAT3 and MMP-13 protein levels increased following downregulation of p21, and this was reversed by treatment with a STAT3 inhibitor. p21-deficient mice were susceptible to OA, and this was associated with increased STAT3 phosphorylation, elevated MMP-13 expression, and elevation of synovial inflammation. The expression of p21 mRNA was decreased and phosphorylation of STAT3 was elevated in human OA chondrocytes.
|
The lack of p21 has catabolic effects by regulation of aggrecan and MMP-13 expression through STAT3 phosphorylation in the cartilage tissue. p21 may function as a regulator of transcriptional factors other than the inhibitor of cell cycle progression in the cartilage tissue. Thus, the regulation of p21 may be a therapeutic strategy for the treatment of OA.
|
27,040,670 |
Does modulation of inflammatory and oxidative status by exercise attenuate cardiac morphofunctional remodeling in experimental Chagas cardiomyopathy?
|
The rational basis that explains the benefits of exercise therapy on Chagas cardiomyopathy (ChC) is poorly understood. This study investigated the impact of an exercise program on exercise performance, heart parasitism, immunoinflammatory response, fibrogenesis, oxidative damage, and cardiomyocytes contractility in experimental ChC. Wistar rats were subjected to a 9-week treadmill running training and challenged with Trypanosoma cruzi. Control animals remained sedentary. Physical and metabolic performance, cardiac morphology, cytokines, chemokines, nitric oxide, oxidative tissue damage, cardiomyocyte morphology and contractility were analyzed. Exercise training was efficient to improve physical performance and anaerobic threshold in trained animals. By increasing cardiac and serum levels of cytokines (TNF-α, IFN-γ, and IL-6), chemokines (MCP-1 and CX3CL1), the myocardial activity catalase and superoxide dismutase, and reducing lipid and protein oxidation in cardiac tissue, exercise training seem to be a beneficial strategy to mitigate the progression and severity of Chagas-associated cardiomyopathy.
|
The protective adaptations to the host triggered by exercise training contributed to reduce cardiac parasitism, inflammation, fibrosis and cardiomyocytes atrophy. Although exercise training does not affect nitric oxide levels in cardiac tissue from infected animals, this strategy enhanced the efficiency of endogenous antioxidant mechanisms, restricting oxidative tissue damage with positive repercussions to cardiomyocytes biomechanics in rats.
|
17,727,931 |
Do we need a new classification for radical hysterectomy?
|
Current surgical treatment of cervical carcinoma is based on the assumption of undirected intra- and transcervical local tumor propagation and is executed by tailored excision of the paracervical tissues. We have recently demonstrated that cervical carcinoma spreads for extended phases during its malignant progression within the permissive compartment of the Müllerian morphogenetic unit (Lancet Oncol 2005;6:751-56) and proposed Müllerian compartment resection as the new principle for surgical treatment of cervical cancer. Do we need a new classification of radical hysterectomy? The therapeutic index of the surgical treatment of cervical carcinoma FIGO stages IB1-IIB by extirpation of the Müllerian compartment through total mesometrial resection (TMMR) without adjuvant radiation is evaluated by an ongoing controlled prospective trial at the University of Leipzig. From 7/1998 to 12/2006, 163 patients with cervical carcinoma, FIGO stages IB1 (n=94), IB2 (n=21), IIA (n=14) and IIB (n=34) have been treated with TMMR and nerve-sparing therapeutic lymph node dissection. Twenty-five patients received (neo)adjuvant chemotherapy. No patient underwent adjuvant radiotherapy although 95 patients (58%) would have needed this additional modality in case of conventional radical hysterectomy because of their high-risk histopathological tumor features. At a median follow-up time of 45 months (3-104 months), recurrence-free and disease-specific overall survival is 93% and 96%. Maximum treatment-related morbidity according to the Franco-Italian score has been grade 2 in 12 patients (8%).
|
The developmental view of local tumor spread and surgical anatomy holds a great promise for improving the therapeutic index of surgical cervical cancer therapy and challenges both the classification of radical hysterectomy based on tailored paracervical resection and the indication for adjuvant radiation.
|
22,093,491 |
Do schools differ in suicide risk?
|
Rates of suicide and poor mental health are high in environments (neighbourhoods and institutions) where individuals have only weak social ties, feel socially disconnected and experience anomie - a mismatch between individual and community norms and values. Young people spend much of their time within the school environment, but the influence of school context (school connectedness, ethos and contextual factors such as school size or denomination) on suicide-risk is understudied. Our aim is to explore if school context is associated with rates of attempted suicide and suicide-risk at age 15 and self-harm at age 19, adjusting for confounders. A longitudinal school-based survey of 1698 young people surveyed when aged 11, (primary school), 15 (secondary school) and in early adulthood (age 19). Participants provided data about attempted suicide and suicide-risk at age 15 and deliberate self-harm at 19. In addition, data were collected about mental health at age 11, social background (gender, religion, etc.), and at age 15, perception of local area (e.g. neighbourhood cohesion, safety/civility and facilities), school connectedness (school engagement, involvement, etc.) and school context (size, denomination, etc.). A dummy variable was created indicating a religious 'mismatch', where pupils held a different faith from their school denomination. Data were analysed using multilevel logistic regression. After adjustment for confounders, pupils attempted suicide, suicide-risk and self-harm were all more likely among pupils with low school engagement (15-18% increase in odds for each SD change in engagement). While holding Catholic religious beliefs was protective, attending a Catholic school was a risk factor for suicidal behaviours. This pattern was explained by religious 'mismatch': pupils of a different religion from their school were approximately 2-4 times more likely to attempt suicide, be a suicide-risk or self-harm.
|
With several caveats, we found support for the importance of school context for suicidality and self-harm. School policies promoting school connectedness are uncontroversial. Devising a policy to reduce risks to pupils holding a different faith from that of their school may be more problematic.
|
26,849,538 |
Do body Composition Changes in Adult Females after Lifestyle Intervention Are Influenced by the NYD-SP18 Variant?
|
The study focuses on the analysis of the possible relationship between a common NYD-SP18 (rs6971091, G>A) gene polymorphism and weight loss after lifestyle intervention (combined dietary intake and physical activity) in overweight/obese females. We genotyped 139 unrelated non-diabetic Czech females (49.5 ± 13.3 years, average BMI at baseline 32.2 ± 4.6 kg/m². Biochemical and anthropometrical measurements were performed before and after ten weeks of lifestyle intervention.
|
Overweight/obese female carriers of the NYD-SP18 rs6971091 GG genotype exhibited a more beneficial response to the intensive lifestyle intervention than others.
|
25,800,823 |
Does viral genotype correlate with distinct liver gene transcription signatures in chronic hepatitis C virus infection?
|
Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or genotype 3 gives rise to distinct pathologies, and the two viral genotypes respond differently to antiviral therapy. To understand these clinical differences, we compared gene transcription profiles in liver biopsies from patients infected with either gt1 or gt3, and uninfected controls. Gt1-infected biopsies displayed elevated levels of transcripts regulated by type I and type III interferons (IFN), including genes that predict response to IFN-α therapy. In contrast, genes controlled by IFN-γ were induced in gt3-infected biopsies. Moreover, IFN-γ levels were higher in gt3-infected biopsies. Analysis of hepatocyte-derived cell lines confirmed that the genes upregulated in gt3 infection were preferentially induced by IFN-γ. The transcriptional profile of gt3 infection was unaffected by IFNL4 polymorphisms, providing a rationale for the reduced predictive power of IFNL genotyping in gt3-infected patients.
|
The interactions between HCV genotypes 1 and 3 and hepatocytes are distinct. These unique interactions provide avenues to explore the biological mechanisms that drive viral genotype-specific differences in disease progression and treatment response. A greater understanding of the distinct host-pathogen interactions of the different HCV genotypes is required to facilitate optimal management of HCV infection.
|
22,426,451 |
Does lumbar bone mass predict low back pain in males?
|
Longitudinal study of lumbar bone mass as predictor of low back pain (LBP). To investigate whether low bone mineral content (BMC) and bone mineral density (BMD) values at the age of 36 years are associated with the prevalence of LBP at the age of 42 years among the study population of the Amsterdam Growth and Health Longitudinal Study. Results of epidemiological, clinical, and in vitro studies indicate that spinal injuries, caused by mechanical loading, might be a cause of LBP. BMC and BMD are determinants of spinal strength. We therefore hypothesized that BMC and BMD are associated with LBP. At the age of 36 years, the lumbar BMC and BMD were determined by dual-energy x-ray absorptiometry in 140 men and 152 women. At the age of 42 years, the participants were asked whether they had experienced LBP in the previous 12 months. Logistic regression analyses were performed to determine odds ratios (ORs)-adjusted for stature, body weight, physical activity, and smoking-for the relationship of BMC and BMD with LBP. BMC and BMD at the age of 36 years were significantly associated with the reported 12-month prevalence of LBP at the age of 42 years. This association, however, was observed only for men and not for women. Men within the quartile with the lowest BMC or BMD values had higher odds for LBP with ORs of 4.78 (95% confidence interval, 1.52-15.00) and 3.48 (95% confidence interval, 1.23-9.85), respectively.
|
For a male population that is not characterized by osteoporosis or old age, lower lumbar BMC and BMD values at the age of 36 years are associated with an increased risk of reporting to have had LBP in the previous 12 months at the age of 42 years.
|
24,812,708 |
Is distal screw entry point associated with subtrochanteric fracture after intracapsular hip fracture fixation?
|
Subtrochanteric fracture is a recognized complication following cannulated screw fixation of intracapsular hip fracture. We investigated the incidence of subtrochanteric fracture in a consecutive series of 304 patients and its association with screw entry point in the lateral femoral cortex. A retrospective consecutive case series of patients treated with internal fixation for intracapsular hip fracture by our unit between January 2003 and January 2010 were included. Two authors reviewed radiographs independently to determine distal screw entry point in the lateral femoral cortex. Hickey zone 1 was an entry point above the level of the upper border of the lesser trochanter. Hickey zone 2 was defined as an entry point between the upper and lower borders of the lesser trochanter. Hickey zone 3 was an entry point below the lower border of the lesser trochanter. Clinical notes were reviewed for subsequent subtrochanteric fracture. Association between subtrochanteric fracture and distal screw entry point in the lateral femoral cortex in relation to the upper border of the lesser trochanter was determined. Two hundred and fifty-six post-operative radiographs were available for analysis. Mean patient age was 73 years (30–98), 75% were women. There were 24 patients with screw entry point in Hickey zone 1, 225 in Hickey zone 2, and 7 in Hickey zone 3. Two patients sustained subtrochanteric fracture. No subtrochanteric fractures occurred in patients with Hickey zone two-screw entry.
|
Subtrochanteric fracture is rare following cannulated screw fixation of intracapsular neck of femur fracture (0.78%). In this retrospective consecutive case series, no subtrochanteric fractures occurred when the entry point of the lowest screw in the lateral femoral cortex is between the levels of the upper and lower borders of the lesser trochanter.
|
22,244,417 |
Pediatric chronic ulcerative colitis: does infliximab increase post-ileal pouch anal anastomosis complications?
|
Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is a common surgical approach to chronic ulcerative colitis (CUC). Preoperative use of Infliximab (IFX) has raised concern of increased postoperative complications. We sought to compare outcomes of pediatric patients (≤ 18 years) who were treated with IFX before IPAA to those who did not. Patients (≤ 18 years of age) who underwent IPAA from 2003 to 2008 for CUC were included, and their records were retrospectively reviewed for preoperative medications, operative technique, and 1-year postoperative complications (leak, wound infection, small bowel obstruction, pouchitis). Subjects were divided into 2 groups--those who received IFX preoperatively and those who did not. Eleven patients received IFX preoperatively, and 27 children did not. All complications following IPAA were more frequent in the IFX group compared to controls (55% vs 26%). Small bowel obstruction was significantly higher in the IFX group (55% vs 7%). Long-term complications occurred in 64% of the IFX group and 61% of the controls.
|
Children that were treated with IFX prior to IPAA suffered twice as many postoperative complications. Long-term outcomes are similar. Currently, we recommend colectomy with end ileostomy for patients that receive IFX within 8 weeks of colectomy for CUC.
|
27,154,034 |
Does influence of Conjunctival fold on Calculated Tear Meniscus Volume Along the Lower Eyelid?
|
In calculating tear meniscus volume (TMV), tear meniscus height (TMH), radius (TMR) and cross-sectional area (TMA) are usually measured at the center of the lower lid margin, but lid-parallel conjunctival folds (LIPCOFs) are known to influence the tear meniscus regularity. The aim of this study was to analyze the influence of LIPCOFs on TMA measured by optical coherence tomography (OCT) and consequently, the calculated tear meniscus volume (TMV). Using OCT (Cirrus-HD; Carl Zeiss Meditec, Jena, Germany), the TMH, TMR and TMA in 42 subjects (13M, 29F; mean age 27.3 SD±8.4 years) were measured directly below the pupil center, plus at temporal and nasal locations perpendicularly below the limbus, where LIPCOFs were also evaluated and graded. TMV for the different locations was calculated. Correlations between LIPCOFs and the tear meniscus parameters were analyzed using the Spearman Rank-Order coefficients. Differences between tear meniscus parameters at the different locations were evaluated by the paired t-test. Central TMV (5.30±1.42 x10(-2)μl/mm) was significantly positively correlated to LIPCOF sum (grade 2.4±1.2) (r=0.422; P<.05). The calculated temporal TMV was greater by 0.53x10(-2)μl/mm compared to the central TMV (P=.037), while there was no significant difference in tear volume between the other locations.
|
Using OCT it was possible to investigate the influence of LIPCOFs on TMH, TMR, and for the first time on TMA, at central and paracentral positions along the lower lid margin. The presence of LICPOF results in an irregularity of tear meniscus with a difference in the amount of predicted tear volume while measuring TMH or TMR at the different locations.
|
17,349,783 |
Does magnetic resonance spectroscopy suggest key differences in the metastatic behaviour of medulloblastoma?
|
Metastatic medulloblastoma has a poorer prognosis than localised disease in part due to inherent properties of the tumour. 1H magnetic resonance spectroscopy (MRS) provides a powerful method for investigating tumour metabolism in vivo. Magnetic resonance imaging and short echo time (Te 30 ms) single voxel MRS were performed on the primary tumour of 16 children with medulloblastoma prior to surgical resection. Tumour volumes were calculated using a segmentation technique and the MRS was analysed using LCModel. Patients with metastatic disease had primary tumours which were smaller (p=0.01), had higher levels of total choline (p=0.03) and lower levels of mobile lipids (p=0.04).
|
Metastatic medulloblastomas have metabolite profiles indicative of increased cell growth and decreased cell death compared with localised tumours reflecting intrinsic differences in underlying biology. Localised tumours with an MRS metabolite profile similar to those with metastatic disease may be at increased risk of metastatic relapse.
|
16,314,589 |
Does subjective social status predict health and change in health status better than objective status?
|
To examine, among middle-aged individuals, if subjective socioeconomic status (SES) predicts health status and change in health status over time better than objective SES. Data are from the Whitehall II study, a prospective study of British civil servants. SES data are drawn from Phase 5 (1997-1999) of the study and health data from Phases 5 and 6 (2000-2001). Physical and mental component scores from the Short Form 36, the General Health Questionnaire, and self-rated health were used to assess health status. Multiple linear regressions were used to examine the relationship between SES and health and change in health status. Complete data were available on 5486 people. Results show both measures of SES to be global measures of SES. Both measures of SES were significantly associated with health outcomes and with decline in health status over time. However, when both objective and subjective measures of SES are entered simultaneously in the model to predict change in health status, it was only the latter that continues to be significantly associated with health and changes in health.
|
Subjective SES is a better predictor of health status and decline in health status over time in middle-aged adults. These results are discussed in terms of three possible explanations: subjective SES is a more precise measure of social position, the results provide support for the hierarchy-health hypothesis, and the results could be an artifact of common method variance.
|
11,028,573 |
Descriptive terms for women attending antenatal clinics: mother knows best?
|
To determine the noun for 'women who attend antenatal clinics' that is most accepted by the women themselves. Cross sectional study. Consultant-led antenatal clinics in Cornwall. All women attending consultant-led antenatal clinics over a two-month period. The women were surveyed by written questionnaire. The first, second and third choices of descriptions offered to women attending antenatal clinics. Secondary outcome measures include the relation of maternal age, gestation, civil status, occupation and obstetric history to the individual's choice of description. Questionnaires were received from 446 women, constituting 13% of the antenatal population of Cornwall. Their median age was 28 years and median gestation 22 weeks; 255 (57%) had one or more children and 289 (65%) were married. The most popular choice of description was 'patient' (39% of first choices made), whereas the most accepted description was 'pregnant woman' (26% of totalled second and third choices). While women who selected 'patient' as first choice were slightly younger (mean 27.5 years) than the remaining women (mean 28.4 years), the choice of 'pregnant woman' was not related to any of the other recorded characteristics of the respondents. Commercial terms that consistently were selected least included 'client', 'consumer' and 'customer'.
|
Some professional bodies and government organisations have criticised the use of the term 'patient' to describe antenatal women. In this, the largest study to investigate what the women themselves would choose, 'patient' is the most favoured term.
|
26,946,928 |
Is low forced expiratory volume in one second associated with the history of acute coronary syndrome in patients with organic coronary stenosis?
|
Chronic obstructive pulmonary disease often coexists with cardiovascular diseases and airflow limitation has been known as a risk of cardiovascular death. However, the association between airflow limitation and the history of acute coronary syndrome (ACS) in patients with coronary stenosis remains to be determined. Study subjects were 271 consecutive patients (age: 70.6±9.5 years, sex: 200 males) who underwent coronary angiography and in whom organic coronary stenosis was detected. We collected spirometric data from those patients and investigated the association of the pulmonary function and the history of ACS. We also compared the prevalence of airflow limitation of the present subjects with Japanese epidemiological data that had been previously published. Multivariate analysis with multiple logistic regression analysis showed that the reduced forced expiratory volume in one second (FEV
|
Reduced FEV
|
9,791,844 |
Does ginseng supplementation enhance healthy young adults ' peak aerobic exercise performance?
|
To determine the short term effects (21 days) of 200 mg (7% standardized) Panax ginseng supplementation vs. placebo on peak aerobic exercise performance in healthy young adults, with unrestricted diets. Twenty men and eight women (age = 23.2 +/- 3.2 years, height = 175.8 +/- 8.6 cm; weight = 75.2 +/- 15.3 kg) were randomly assigned to either a Panax ginseng or placebo group for a period of 3 weeks in a double blind design. Prior to and following treatment the subjects performed a symptom limited graded exercise test on a Schwinn Airdyne ergometer. The data were analyzed using an analysis of variance. No significant treatment effect was observed for the dependent variables of VO2, exercise time, workload, plasma lactate and hematocrit at peak levels, or for heart rate and rate of perceived exertion at 150 watts, 200 watts and peak.
|
The results of this study do not support an ergogenic effect on peak aerobic exercise performance following a 3-week supplementation period of 200 mg 7% Panax ginseng in healthy young adults with moderate exercise capacities and unrestricted diets.
|
18,355,912 |
Expansion of hepatitis C-specific CD4+CD25+ regulatory T cells after viral clearance: a mechanism to limit collateral damage?
|
Data from rodent models suggest that a subpopulation of CD4+ T cells, characterized by the constitutive expression of CD25, play a key role in regulating many immune responses. Human CD4+CD25+ T cells also appear to possess a regulatory function, but their role in infections is not fully defined. We sought to explore the possibility of a role for CD4+CD25+ T cells in controlling immunity to hepatitis C virus (HCV). We hypothesized that CD4+CD25+ T cells might account for the paucity of immune responses measurable in chronically viremic patients by suppressing the immune responses to HCV antigens. We compared the responses of PBMCs to 3 different recombinant HCV antigens before and after depletion of CD25+ cells in 15 chronically viremic patients, 14 nonviremic HCV antibody-positive subjects, and 14 healthy control subjects. We also tested the ability of CD4+CD25+ T cells purified from HLA-matched viremic or nonviremic blood to suppress the responses of HCV epitope-specific T-cell clones. To our surprise, depletion of peripheral blood CD25+ cells led to a pronounced increase in proliferation of and IFN-gamma production by PBMCs only in nonviremic patients. Furthermore, the CD4+CD25+ T cells purified from HLA-matched nonviremic blood (in contrast to CD4+CD25+ T cells isolated from chronically viremic blood) inhibited the responses of HCV epitope-specific T-cell clones.
|
HCV-specific CD4+CD25+ regulatory T cells appear to accompany successful viral clearance.
|
25,011,471 |
Is anti-inflammatory effect of caffeine associated with improved lung function after lipopolysaccharide-induced amnionitis?
|
Although caffeine enhances respiratory control and decreases the need for mechanical ventilation and resultant bronchopulmonary dysplasia, it may also have anti-inflammatory properties in protecting lung function. We hypothesized that caffeine improves respiratory function via an anti-inflammatory effect in lungs of a lipopolysaccharide (LPS)-induced pro-inflammatory amnionitis rat pup model. Caffeine was given orally (10 mg/kg/day) from postnatal day (p)1 to p14 to pups exposed to intra-amniotic LPS or normal saline. Expression of IL-1β was assessed in lung homogenates at p8 and p14, and respiratory system resistance (Rrs) and compliance (Crs) as well as CD68 cell counts and radial alveolar counts were assessed at p8. In LPS-exposed rats, IL-1β and CD68 cell counts both increased at p8 compared to normal saline controls. These increases in pro-inflammatory markers were no longer present in caffeine-treated LPS-exposed pups. Rrs was higher in LPS-exposed pups (4.7 ± 0.9 cm H2O/ml·s) at p8 versus controls (1.6 ± 0.3 cm H2O/ml·s, p < 0.01). LPS-exposed pups no longer exhibited a significant increase in Rrs (2.8 ± 0.5 cm H2O/ml·s) after caffeine. Crs did not differ significantly between groups, although radial alveolar counts were lower in both groups of LPS-exposed pups.
|
Caffeine promotes anti-inflammatory effects in the immature lung of prenatal LPS-exposed rat pups associated with improvement of Rrs, suggesting a protective effect of caffeine on respiratory function via an anti-inflammatory mechanism.
|
15,569,977 |
Does epigenetic inactivation of ID4 in colorectal carcinomas correlate with poor differentiation and unfavorable prognosis?
|
ID4 gene is a member of the inhibitor of DNA binding (ID) family proteins that inhibit DNA binding of basic helix-loop-helix transcription factors. The epigenetic inactivation of ID4 gene on colorectal cancer (CRC) development and its clinical significance was assessed. In CRC cell lines, ID4 methylation status of the promoter region was assessed by methylation-specific PCR and bisulfite sequencing. The mRNA expression level was assessed by quantitative real-time reverse transcription-PCR. The methylation status of 9 normal epithelia, 13 adenomas, 92 primary CRCs, and 26 liver metastases was assessed by methylation-specific PCR. ID4 protein expression was assessed by immunohistochemistry analysis of tissue specimen. CRC cell lines were shown to be hypermethylated, and mRNA expression was suppressed and could be restored by 5-aza-cytidine treatment. In clinical specimens from normal epithelia, adenomas, primary CRCs, and liver metastases, the frequency of ID4 hypermethylation was 0 of 9 (0%), 0 of 13 (0%), 49 of 92 (53%), and 19 of 26 (73%), respectively, with a significant elevation according to CRC pathological progression. Methylation status of primary CRCs significantly correlated with histopathological tumor grade (P = 0.028). Immunohistochemistry analysis showed ID4 expression of normal colon epithelia, adenomas, and unmethylated primary CRCs but not hypermethylated CRC specimens. Among 76 American Joint Committee on Cancer stage I to IV patients who had undergone curative surgical resection, overall survival was significantly poorer in patients with hypermethylated ID4 bearing tumors (P = 0.0066).
|
ID4 gene is a potential tumor suppressor gene for which methylation status may play an important role in the CRC progression.
|
23,672,313 |
Is presence of C11orf95-MKL2 fusion a consistent finding in chondroid lipomas : a study of eight cases?
|
Chondroid lipomas are benign adipose tissue tumours. Their rarity and peculiar morphology can lead to misinterpretation, especially in small biopsies. Based on a recurrent translocation t(11;16)(q13;p13), the C11orf95-MKL2 fusion gene has been found in a few cases. Therefore, it seemed appropriate to look for this fusion gene in a larger cohort. We describe eight further cases from four females and four males with an age range of 21-81 years (median 49 years). The tumours were situated in the lower arm (three), lower leg (two), thigh (one), back (one) and head (one); seven lesions were deep-seated and one was located subcutaneously. Sizes ranged from 3 to 12 cm (median 6.3 cm). All patients were treated by simple excision, and follow-up, available for six patients (range 2 months-12 years; median 15 months), demonstrated recurrence in one case. Histologically, the circumscribed and lobulated tumours showed a variable composition of adipocytes, lipoblasts, hibernoma-like cells and chondroblast-like cells embedded in a chondroid matrix. Immunohistochemistry, performed in four cases, revealed positivity for S-100 and pancytokeratin in two of three neoplasms stained for each marker. A C11orf95-MKL2 fusion gene was shown by RT-PCR analysis in seven of the eight cases.
|
Molecular analysis can be used to support the diagnosis of chondroid lipoma, especially in small samples. This may be helpful in planning treatment when the differential diagnosis includes malignant lesions.
|
2,656,959 |
Acetaminophen: more harm than good for chickenpox?
|
To determine whether acetaminophen affects the duration or severity of childhood varicella. Randomized, double-blind, placebo-controlled trial. Office- and hospital-based pediatric practices. Seventy-two children between 1 and 12 years of age entered the study. One child was withdrawn because of high fever, and three children did not complete the study; 31 received placebo and 37 received acetaminophen. Acetaminophen, 10 mg/kg/dose, was given at 8 AM, 12 PM, 4 PM, and 8 PM for 4 days. Placebo was given to the control group. Itching, appetite, activity, and overall condition were measured for 6 days. The time to last vesicle formation, time to total scabbing, and time to total healing were measured until complete resolution of the exanthem. The following results were better in the placebo group (p less than .05): time to total scabbing 5.6 days (SD 2.5) versus 6.7 days (SD 2.3) in the acetaminophen group, and itching on day 4 in the placebo group (symptom score 2.9 (SD 0.20) vs 2.2 (SD 0.26]. Activity was better in the acetaminophen group on day 2 (3.13 (SD 0.23) vs 2.82 (SD 0.24].
|
These results provide evidence that acetaminophen does not alleviate symptoms in children with varicella and may prolong illness.
|
25,374,254 |
Does phosphorylation in intrinsically disordered regions regulate the activity of Neurogenin2?
|
Neuronal differentiation is largely under the control of basic Helix-Loop-Helix (bHLH) proneural transcription factors that play key roles during development of the embryonic nervous system. In addition to well-characterised regulation of their expression, increasing evidence is emerging for additional post-translational regulation of proneural protein activity. Of particular interest is the bHLH proneural factor Neurogenin2 (Ngn2), which orchestrates progression from neural progenitor to differentiated neuron in several regions of the central nervous system. Previous studies have demonstrated a key role for cell cycle-dependent multi-site phosphorylation of Ngn2 protein at Serine-Proline (SP) sites for regulation of its neuronal differentiation activity, although the potential structural and functional consequences of phosphorylation at different regions of the protein are unclear. Here we characterise the role of phosphorylation of specific regions of Ngn2 on the stability of Ngn2 protein and on its neuronal differentiation activity in vivo in the developing embryo, demonstrating clearly that the location of SP sites is less important than the number of SP sites available for control of Ngn2 activity in vivo. We also provide structural evidence that Ngn2 contains large, intrinsically disordered regions that undergo phosphorylation by cyclin-dependent kinases (cdks).
|
Phosphorylation of Ngn2 occurs in both the N- and C-terminal regions, either side of the conserved basic Helix-Loop-Helix domain. While these phosphorylation events do not change the intrinsic stability of Ngn2, phosphorylation on multiple sites acts to limit its ability to drive neuronal differentiation in vivo. Phosphorylated regions of Ngn2 are predicted to be intrinsically disordered and cdk-dependent phosphorylation of these intrinsically disordered regions contributes to Ngn2 regulation.
|
25,820,470 |
Is family CHAOS associated with glycaemic control in children and adolescents with type 1 diabetes mellitus?
|
Despite advances in the medical management of type 1 diabetes mellitus (T1DM), for many, glycaemic control remains substandard. Other factors are clearly important in determining success, or lack thereof, with diabetes management. With this in mind, we have investigated whether family CHAOS may provide a novel tool to identify when environmental confusion could impact on diabetes management and subsequent glycaemic control. A case-control study of children and adolescents with established T1DM and age-/sex-matched controls was conducted. Demographic information, both maternal and paternal CHAOS scores, and HbA1c were collected. Statistical analysis was undertaken to explore associations between T1DM and CHAOS and between CHAOS and HbA1c. Data on 65 children with T1DM and 60 age-/sex-matched controls were obtained. There was no evidence of group differences for maternal CHAOS (p = 0.227), but paternal CHAOS scores were higher for the T1DM group (p = 0.041). Greater maternal and paternal CHAOS scores were both associated with higher HbA1c (p ≤ 0.027). The maternal association remained after controlling for diabetes duration, SMBG frequency, and insulin therapy.
|
In children with T1DM, there appears to be a negative association between increased environmental confusion, as rated by CHAOS, and glycaemic control. In addition, when compared to controls, fathers of children and adolescents with T1DM appear to experience CHAOS differently to mothers. These findings contribute to the growing body of literature exploring psychosocial factors in T1DM. Continuing efforts are required to fully understand how the family and psychosocial environment interact with diabetes to impact on long-term health outcomes.
|
19,461,478 |
Do kidneys from deceased donors more than 75 years perform acceptably after transplantation?
|
Organ shortage has resulted in an increased use of expanded criteria donors for transplantation, in particular kidneys from older donors. There is limited data on the impact of donor age more than 75 years on kidney transplant outcome. A retrospective single-center analysis on deceased donors more than 75 years and kidney transplant outcome in an old for old setting was performed. Histologic findings (global kidney score) in graft biopsies and deceased-donor scores were evaluated to observe if this information could be helpful in predicting outcome. Evaluation of data from 54 single kidney transplantations from 29 donors more than 75 years (median 77.5, range 75.2-86.1) were assessed. Ninety-three percent of the donors died of intracranial bleeding, and 69% had a history of hypertension or cardiovascular event(s). Median recipient age was 70.1 (range 50.6-82.4). Fifty-two grafts (96%) had posttransplant function. Death censored graft survival at 1, 3, and 5 years were 87%, 83%, and 83%, respectively. Patient survival was 81%, 75%, and 59% at the same time points. At follow-up at median 23 months (range 6-144 months), thirty-five recipients were alive with a median serum creatinine of 163 micromol/ L (range 103-348). Global kidney score and deceased donor score did not predict graft outcome.
|
Kidney transplants from deceased donors more than 75 years perform acceptable as single transplants and should be considered for use in older recipients.
|
23,141,854 |
Is minor myocardial damage a prevalent condition in patients with acute heart failure syndromes and preserved systolic function with long-term prognostic implications : a report from the CIAST-HF ( Collaborative Italo-Argentinean Study on cardiac Troponin T in Heart Failure ) study?
|
Half of patients with acute heart failure syndromes (AHFS) have preserved left ventricular ejection fraction (PLVEF). In this setting, the role of minor myocardial damage (MMD), as identified by cardiac troponin T (cTnT), remains to be established. To evaluate the prevalence and long-term prognostic significance of cTnT elevations in patients with AHFS and PLVEF. This retrospective, multicenter, collaborative study included 500 patients hospitalized for AHFS with PLVEF (ejection fraction ≥40%) between October 2000 and December 2006. Blood samples were collected within 12 hours after admission and were assayed for cTnT. MMD was defined as a cTnT value of ≥0.020 ng/mL. Mean age was 73 ± 12 years, 47% were female, 38% had an ischemic etiology, and New York Heart Association (NYHA) class was 2.2 ± 0.7. Mean cTnT value was 0.149 ± 0.484 ng/mL, and cTnT was directly correlated with serum creatinine (Spearman's Rho = 0.35, P < .001) and NYHA class (0.25, P < .001). MMD was diagnosed in 220 patients (44%). Patients with MMD showed lower left ventricular ejection fraction (P < .05), higher serum creatinine (P < .001), higher prevalence of ischemic etiology and diabetes mellitus, a worse NYHA class (P < .001), and higher natriuretic peptide levels (P < .001) as compared with patients without MMD. At 6-month follow-up, overall event-free survival was 55% and 75% in patients with and without MMD (P < .001), respectively. On multivariate Cox regression analysis, only NYHA class (HR = 1.50; P = .002) and MMD (HR = 1.81; P = .001) were identified as predictors of events.
|
Increased cTnT levels were detected in approximately 50% of patients with AHFS with preserved systolic function, and were found to correlate with clinical measures of disease severity. The presence of MMD was associated with a worse long-term outcome, lending support to cTnT-based risk stratification in the setting of AHFS.
|
7,887,661 |
Are melanoma and vitiligo associated with antibody responses to similar antigens on pigment cells?
|
Several clinical observations suggest that there is a link between vitiligo and melanoma. We examined whether an immune response to similar antigens on pigment cells could account for this association. We tested 30 patients with melanoma, 29 patients with vitiligo, and 28 patients with unrelated conditions for antibodies to human melanocyte antigens using an immunoprecipitation sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis assay. Antibodies to melanocytes were present in 24 (80%) patients from the melanoma group, 24 (83%) patients from the vitiligo group, and in two (7%) patients from the control group. The antibodies in patients with melanoma or vitiligo were directed to similar antigens with molecular weights of approximately 40 to 45, 75, and 90 kd. The frequency of antibody responses to each of these antigens was similar in both diseases. By sequential immunodepletion, the antigens defined by antibodies in both diseases were similar. These antigens were also expressed on melanoma cells.
|
Most patients with melanoma or with vitiligo develop antibodies to similar antigens that are present both on melanocytes and on melanoma cells. These findings support the hypothesis that the clinical link between the two diseases results from immune responses to antigens shared by normal and malignant pigment cells.
|
16,336,328 |
Is preoperative serum prostate-specific antigen level significantly related to clinical recurrence after radical retropubic prostatectomy for localized prostate cancer?
|
To evaluate the influence of preoperative serum prostate-specific antigen (PSA) level and other clinicopathological variables on the probability of biochemical failure and clinical recurrence after radical prostatectomy (RP) for localized prostate cancer. The study was a retrospective survival analysis in 211 patients undergoing retropubic RP for clinically localized prostate cancer in the period 1988-2000. Survival was estimated using the Kaplan-Meier method; survival endpoints were biochemical failure, defined as a PSA level of>or = 0.5 ng/mL or clinical recurrence consisting of palpable tumours in the prostatic fossa or distant metastases. In 58 patients with biochemical failure after surgery, we assessed the impact of the doubling time of serum PSA level (PSADT) on the risk of developing skeletal metastases or local recurrence. The median (range) observation period was 66 (9-160) months. Biochemical failure occurred in 92 patients (44%) of whom 39 (42%) had local recurrence or skeletal metastases. There was a highly significant association (P<0.001) between clinical T stage, histological grade, capsular penetration, surgical margin status, seminal vesicle invasion, preoperative serum PSA level and the probability of biochemical failure-free survival. By contrast there was no statistically significant association between preoperative serum PSA level, clinical T stage, surgical margin status, and clinical recurrence. There was a significant relationship between age (P = 0.021), histological grade (P = 0.025), capsular penetration (P = 0.018), seminal vesicle invasion (P = 0014), and clinical recurrence. Cox regression analysis showed that only histological grade and seminal vesicle invasion were independent predictors of clinical recurrence. In a subgroup of 58 patients with a rising serum PSA level after RP, a PSADT of<or = 12.8 months conferred a significantly higher risk (P = 0.015) of developing skeletal metastases than a PSADT of>12.8 months.
|
In the present patients undergoing RP the preoperative serum PSA level was not associated with the clinical outcome, whereas it was significantly related to biochemical failure rate. The probability of skeletal metastases was significantly associated with the PSADT after biochemical failure.
|
21,112,136 |
Is brachial artery conductance during reactive hyperemia increased in women with polycystic ovary syndrome?
|
To examine changes in brachial artery conductance (BAC) during reactive hyperemia in women with polycystic ovary syndrome (PCOS) compared to controls. This is a pilot case-control study performed at a single academic medical center. Changes in BAC during reactive hyperemia were evaluated in 31 women with PCOS and 11 healthy control women. Fasting glucose, insulin, lipids and androgen levels were also determined. A mixed-effects model was used to compare the PCOS curve to the control curve for change in BAC from baseline during reactive hyperemia. Body mass index (BMI) and testosterone levels were significantly increased in the PCOS group compared to controls (P<0.05). In addition, the PCOS group had higher total and LDL cholesterol levels (P=0.05 and 0.09, respectively). Change in BAC from baseline during reactive hyperemia was significantly increased in the PCOS group compared to controls even after adjusting for age, BMI and LDL cholesterol levels (P<0.0001). There were no significant differences between the two groups in age, blood pressure, or fasting glucose or insulin levels.
|
Brachial artery conductance during reactive hyperemia is significantly increased in women with PCOS compared to controls and may be a novel early indicator of increased cardiovascular risk in women with PCOS.
|
22,105,462 |
Does central nervous system regeneration occur?
|
Review. To examine the state of research in central nervous system (CNS) regeneration and to suggest an alternative to the sterile research at the lesion site. Worldwide. A search of publications using 'PubMed' and a search of the historical literature relevant to CNS regeneration, biological models, the neurone theory, collateral sprouting, spinal shock and the central pattern generator. There is no evidence for CNS regeneration.
|
A century of research focussed on the lesion site has been unproductive. An alternative field of research must be developed and the best candidate is the undamaged CNS.
|
26,495,941 |
The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection?
|
Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. The value of extent of resection (EOR) in improving survival in patients with GBM has been repeatedly confirmed, with more extensive resections providing added advantages. The authors reviewed the survival of patients with significant EORs and assessed the relative benefit/risk of resecting 100% of the MRI region showing contrast-enhancement with or without additional resection of the surrounding FLAIR abnormality region, and they assessed the relative benefit/risk of performing this additional resection. The study cohort included 1229 patients with histologically verified GBM in whom ≥ 78% resection was achieved at The University of Texas MD Anderson Cancer Center between June 1993 and December 2012. Patients with>1 tumor and those 80 years old or older were excluded. The survival of patients having 100% removal of the contrast-enhancing tumor, with or without additional resection of the surrounding FLAIR abnormality region, was compared with that of patients undergoing 78% to<100% EOR of the enhancing mass. Within the first subgroup, the survival durations of patients with and without resection of the surrounding FLAIR abnormality were subsequently compared. The data on patients and their tumor characteristics were collected prospectively. The incidence of 30-day postoperative complications (overall and neurological) was noted. Complete resection of the T1 contrast-enhancing tumor volume was achieved in 876 patients (71%). The median survival time for these patients (15.2 months) was significantly longer than that for patients undergoing less than complete resection (9.8 months; p<0.001). This survival advantage was achieved without an increase in the risk of overall or neurological postoperative deficits and after correcting for established prognostic factors including age, Karnofsky Performance Scale score, preoperative contrast-enhancing tumor volume, presence of cyst, and prior treatment status (HR 1.53, 95% CI 1.33-1.77, p<0.001). The effect remained essentially unchanged when data from previously treated and previously untreated groups of patients were analyzed separately. Additional analyses showed that the resection of ≥ 53.21% of the surrounding FLAIR abnormality beyond the 100% contrast-enhancing resection was associated with a significant prolongation of survival compared with that following less extensive resections (median survival times 20.7 and 15.5 months, respectively; p<0.001). In the multivariate analysis, the previously treated group with<53.21% resection had significantly shorter survival than the 3 other groups (that is, previously treated patients who underwent FLAIR resection ≥ 53.21%, previously untreated patients who underwent FLAIR resection<53.21%, and previously untreated patients who underwent FLAIR resection ≥ 53.21%); the previously untreated group with ≥ 53.21% resection had the longest survival.
|
What is believed to be the largest single-center series of GBM patients with extensive tumor resections, this study supports the established association between EOR and survival and presents additional data that pushing the boundary of a conventional 100% resection by the additional removal of a significant portion of the FLAIR abnormality region, when safely feasible, may result in the prolongation of survival without significant increases in overall or neurological postoperative morbidity. Additional supportive evidence is warranted.
|
9,719,169 |
Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients?
|
It has been suggested that the vitamin D receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone metabolism. To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 88 haemodialysed patients not receiving active vitamin D metabolites. Whole body, lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline phosphatase activity and intact 1,84 PTH levels were measured. VDR genotype BB, Bb and bb were found in 27, 49 and 24% of patients. Initial BMD (g/cm2) of whole body, lumbar spine and femoral neck did not differ between genotypes (whole body: BB 1.055 +/- 0.120, Bb 1.082 +/- 0.102, bb 1.128 +/- 0.120; lumbar spine: BB 1.075 +/- 0.199, Bb 1.079 +/- 0.185, bb 1.099 +/- 0.170; femoral neck: BB 0.808 +/- 0.160, Bb 0.862 +/- 0.127, bb 0.842 +/- 0.125; mean +/- SD), but the decrease of whole body and femoral neck BMD during 18 months was significantly (P<0.02) different between the genotype groups (whole body: BB -0.048 +/- 0.028, Bb -0.031 +/- 0.029, bb -0.024 +/- 0.023; femoral neck BB -0.044 +/- 0.069, Bb -0.032 +/- 0.081, bb -0.012 +/- 0.029 g/cm2).
|
This preliminary study suggests faster mineral loss in BB genotype of VDR in haemodialysed patients.
|
18,729,301 |
Is the inhibition of insulin-stimulated proliferation of vascular smooth muscle cells by rosiglitazone mediated by the Akt-mTOR-P70S6K pathway?
|
Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27Kip1 and retinoblastoma protein (RB). However, the upstream signaling mechanisms associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase pathway is the central regulator of cell growth and proliferation, and increases cell proliferation by inhibiting the activities of p27Kip1 and retinoblastoma protein (RB). Therefore, we hypothesized in this study that rosiglitazone inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K signaling pathway. Rat aortic smooth muscle cells (RAoSMCs) were treated with 10microM of rosiglitazone 24 hours before the addition of insulin as a mitogenic stimulus. Western blot analysis was performed to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR-P70S6K signaling pathway. Carotid balloon injury was also performed in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3 mg/kg of rosiglitazone. Western blot analysis demonstrated significant inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex.
|
The inhibitory effect of rosiglitazone on RAoSMC proliferation in vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.
|
19,033,720 |
Does combination therapy with paricalcitol and enalapril ameliorate cardiac oxidative injury in uremic rats?
|
This study investigated the protective effect of the angiotensin-converting enzyme inhibitor, enalapril, and the vitamin D analog, paricalcitol, alone or in combination, on cardiac oxidative stress in uremic rats. Rats were made uremic by 5/6 nephrectomy and treated for 4 months as follows: (1) uremic + vehicle (n = 11); (2) uremic + enalapril (30 mg/l in drinking water, n = 13); (3) uremic + paricalcitol (200 ng 3x week, n = 6); (4) uremic + enalapril + paricalcitol (n = 14), and (5) controls (n = 6). Cardiac NADPH oxidase activity increased by 300% in uremic rats compared to normal controls. Treatment with enalapril, paricalcitol or the combination of the two protected uremic rats from cardiac oxidative stress by inhibiting enzyme activity. Cardiac malondialdehyde (MDA) levels were significantly increased in uremic rats compared to normal controls. Only the combination therapy inhibited the increase in MDA levels in uremic rats. Cardiac glutathione was significantly reduced in uremic rats compared to normal controls. Enalapril, paricalcitol or the two in combination all protected against this reduction in glutathione. Cardiac copper/zinc superoxide dismutase (CuZn-SOD) activity decreased whereas manganese (Mn-SOD) activity increased in uremic rats compared to controls. Both mono and combination therapies ameliorated the alterations in cardiac SOD activity seen in uremic rats.
|
Enalapril, paricalcitol and their combined therapy afford protection against cardiac oxidative stress in uremia.
|
24,713,326 |
Does the presence of a depressive episode predict lower return to work rate after myocardial infarction?
|
No studies have evaluated whether the presence of a depressive episode is associated with an increased risk of not returning to work following myocardial infarction (MI). To examine the prospective associations between depressive episode and anxiety disorders with return to work (RTW) after MI at 3 and 12 months based on International Classification of Diseases, 10th Revision. Prospective cohort study. Four hospitals in the North of The Netherlands. From a sample of patients hospitalized for MI (n=487), we selected those who had a paid job at the time of the MI (N=200). Presence of a depressive episode and presence of any anxiety disorder during the first 3 months post-MI. RTW at 12 months post-MI. Of the patients with work prior to MI, 75% had returned to work at 12 months. The presence of a depressive episode during the first 3 months (prevalence: 19.4%) was a significant predictor of no RTW at 12 months post-MI, also after controlling for confounders [odds ratio (OR) 3.48; 95% confidence interval (CI): 1.45-8.37]. The presence of an anxiety disorder (prevalence: 11.9%) had a borderline significant association with no RTW as well. This association remained after controlling for confounders (OR 2.90; 95% CI: 1.00-6.38) but diminished when controlling for depression.
|
The presence of a depressive episode was associated with an increased risk of no RTW in MI patients. The association between anxiety and risk of no RTW could in part be explained by the presence of depression. Further studies may address the possibility of countering the effect of depression by effective treatment.
|
12,700,010 |
Is short stature related to high body fat composition despite body mass index in a Mexican population?
|
Mexico has a high prevalence of short stature (SS) population; thus, body mass index (BMI) criteria for diagnosis of obesity should be different from that in a tall stature (TS) population. The aim of this study was to determine whether SS at the same BMI would have greater body fat mass than those with TS. We studied 116 individuals, 58 with SS (women < or =1.50 m and men < or =1.60 m) matched by gender, age (+/-5 years), and BMI (+/-2). Body fat was measured by bioelectrical impedance analysis. Paired comparisons between matched subjects showed that SS have greater body fat percentage than TS (Delta = 1.40%, p = 0.04). Subjects with BMI > or =25 and SS showed higher difference (Delta = 4.2%, p = 0.004) in body fat percentage. Subjects with SS have more body fat percentage than TS.
|
This finding supports the hypothesis that in SS population BMI for diagnosis of obesity must be re-evaluated; from these results, we propose that diagnosis of obesity in SS be from BMI of 25.
|
21,254,290 |
Do people regard cheaper medicines effective?
|
Generic substitution (GS) is an important way to decrease medical costs. We aimed to study the opinions and attitudes of Finnish people about GS five years after it was introduced, the reasons for substituting and what people think about generic medicines. We sent a postal survey to a random stratified population sample of 3000 Finnish people aged at least 18 years in 2008. The random sample was drawn from five mainland counties. The sampling was conducted by the Finnish Population Register Centre. The response rate was 62% (n=1844) after exclusion of unobtainable addressees (n=34). Most of the respondents (70.9%) considered GS a good law reform. However, there were many respondents who were unsure about their opinion (26.9%). The respondents also held the opinion that cheaper medicines are effective (80.9%) and that GS does not cause any risk to drug safety (84.9%). Most of the respondents (88.4%) who had substituted their medicines had not noticed any difference between the previously used and substituted medicines. Two main reasons for substituting were a desire to save money and recommendation by pharmacists. Of the respondents, 16.3% had experience with both substituting and refusing it. The percentage of the respondents who only had experience with refusing GS was 8.6%. Female gender, older age and use of prescription drugs were associated with refusing.
|
Finnish people consider GS a good reform. They also have confidence in the effect of cheaper medicines. Savings are the main reason for accepting GS.
|
17,242,279 |
Does increased expression of syndecan-1 protect against cardiac dilatation and dysfunction after myocardial infarction?
|
The cell-associated proteoglycan syndecan-1 (Synd1) closely regulates inflammation and cell-matrix interactions during wound healing and tumorigenesis. The present study investigated whether Synd1 may also regulate cardiac inflammation, matrix remodeling, and function after myocardial infarction (MI). First, we showed increased protein and mRNA expression of Synd1 from 24 hours on, reaching its maximum at 7 days after MI and declining thereafter. Targeted deletion of Synd1 resulted in increased inflammation and accelerated, yet functionally adverse, infarct healing after MI. In concordance, adenoviral gene expression of Synd1 protected against exaggerated inflammation after MI, mainly by reducing transendothelial adhesion and migration of leukocytes, as shown in vitro. Increased inflammation in the absence of Synd1 resulted in increased monocyte chemoattractant protein-1 expression, increased activity of matrix metalloproteinase-2 and -9, and decreased activity of tissue transglutaminase, associated with increased collagen fragmentation and disorganization. Exaggerated inflammation and adverse matrix remodeling in the absence of Synd1 increased cardiac dilatation and impaired systolic function, whereas gene overexpression of Synd1 reduced inflammation and protected against cardiac dilatation and failure.
|
Increased expression of Synd1 in the infarct protects against exaggerated inflammation and adverse infarct healing, thereby reducing cardiac dilatation and dysfunction after MI in mice.
|
25,069,759 |
Does interferon α-2b gain high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation?
|
This open-label, prospective, observational study aimed to evaluate treatment response, efficacy therapy and safety to IFN α-2b for the essential thrombocythemia (ET) and polycythemia vera (PV) with JAK2V617F positive mutation. A total of 123 ET patients received IFNα-2b therapy with JAK2V617F positive or negative mutation; and 136 PV patients with JAK2V617F(+) received IFNα-2b or hydroxyurea (HU) therapy according to random number assignment (ages 18-65 years old). ET patients receiving IFN α-2b with JAK2V617F(+) had a greater advantage in overall hematologic response (OHR) than JAK2V617F(-) (83.3% versus 61.4%, P<0.01). For PV patients with JAK2V617F(+), IFN had no OHR superiority to HU (70.3% versus 70.8%, P>0.05), but which gained a greater satisfactory molecular response than HU (54.7% versus 19.4%, P<0.01). IFN significantly decreased the phlebotomy rate, which was better than HU for MPDs patients with OHR than HU (3.6% versus 65.7%, P<0.01). Furthermore, ET patients with JAK2V617F(+) demonstrated a definite advantage over JAK2V617F(-) in five-year PFS (75.9% versus 47.6%, P<0.05). For PV patients with JAK2V617F(+), IFN α-2b was superior to HU in five-year PFS (66.3% versus 46.7%, P<0.01). Moreover, IFN α-2b also contributed to improved vasomotor symptoms in MPDs, and especially significantly decreased the incidence of distal paresthesias (14.1% versus 37.5%) and erythromelalgia (9.4% versus 29.2%) better than HU (P<0.01). Meanwhile, IFN did not observe the severe hematological adverse events in patients with PV or ET.
|
The data confirmed that IFN α-2b benefited the patients with ET or PV, particularly for JAK2V617F(+) mutation.
|
23,262,249 |
Does non-selective betablocker therapy decrease intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis?
|
We evaluated the gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior to and after non-selective betablocker (NSBB) treatment. Hepatic venous pressure gradient (HVPG) was measured prior to and under NSBB treatment. Gastroduodenal and intestinal permeability was assessed by the sucrose-lactulose-mannitol (SLM) test. Anti-gliadin and anti-endomysial antibodies were measured. Levels of LPS-binding protein (LBP) and interleukin-6 (IL-6) were quantified by ELISA, and NOD2 and toll-like receptor 2 (TLR2) polymorphisms were genotyped. Fifty cirrhotics were included (72% male, 18% ascites, 60% alcoholic etiology). Abnormal gastroduodenal and intestinal permeability was found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ≥20 mm Hg; n=35) had increased markers of gastroduodenal/intestinal permeability (urine sucrose levels p=0.049; sucrose/mannitol ratios p=0.007; intestinal permeability indices p=0.002), and bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG <20 mm Hg. A substantial portion of patients showed elevated levels of anti-gliadin antibodies (IgA: 60%, IgG: 34%) whereas no anti-endomysial antibodies were detected. A significant correlation of portal pressure (i.e., HVPG) with all markers of gastroduodenal/intestinal permeability and with LBP and IL-6 levels was observed. NOD2 and TLR2 risk variants were associated with abnormal intestinal permeability and elevated markers of bacterial translocation. At follow-up HVPG measurements under NSBB, we found an amelioration of gastroduodenal/intestinal permeability and a decrease of bacterial translocation (LBP - 16% p=0.018; IL-6 - 41% p<0.0001) levels, which was not limited to hemodynamic responders. Abnormal SLM test results and higher LBP/IL-6 levels were associated with a higher risk of variceal bleeding during follow-up but not with mortality.
|
Abnormal gastroduodenal/intestinal permeability, anti-gliadin antibodies, and bacterial translocation are common findings in cirrhotic patients and are correlated with the degree of portal hypertension. NSBB treatment ameliorates gastroduodenal/intestinal permeability and reduces bacterial translocation partially independent of their hemodynamic effects on portal pressure, which may contribute to a reduced risk of variceal bleeding.
|
20,651,634 |
Is decompressive craniectomy an independent risk factor for communicating hydrocephalus in patients with increased intracranial pressure?
|
It was recently suggested that communicating hydrocephalus is an almost universal finding after hemicraniectomy and that early cranioplasty may prevent the need for permanent cerebrospinal fluid diversion in these patients. To conduct a study in an attempt to verify these findings. The medical records of all patients who underwent decompressive craniectomy for medically refractory elevated intracranial pressure between 2001 and 2009 were retrospectively reviewed. Patients with subarachnoid hemorrhage, intraventricular hemorrhage, or head trauma were excluded. Hydrocephalus was classified as internal or external and as clinically significant or asymptomatic. The patient population consisted of 17 patients, 8 men and 9 women, with a median age of 44 years (range, 27-53 years). Etiologies included malignant middle cerebral artery territory infarction in 12 patients, hemorrhagic transformation of ischemic cerebrovascular accident in 2 patients, dural sinus thrombosis in 2 patients, and hemorrhagic cerebrovascular accident in 1 patient. The extent of craniectomy ranged from a large bone flap in 4 patients to a standard hemicraniectomy in 13 patients. Two patients died and 1 was lost to follow-up during the acute stage. The remaining 14 patients underwent cranioplasty after a median interval of 21 days (range, 3-42 days). In none of these patients did clinically significant hydrocephalus develop requiring cerebrospinal fluid diversion. Asymptomatic extra-axial cerebrospinal fluid collections developed in 2 patients that resolved spontaneously after cranioplasty.
|
Our results suggest that, contrary to some beliefs, hydrocephalus does not frequently occur after decompressive craniectomy.
|
23,777,397 |
Does social identity influence stress appraisals and cardiovascular reactions to acute stress exposure?
|
This study tested a recent theoretical development in stress research to see whether group membership influenced cardiovascular reactions following exposure to acute stress. Participants (N = 104) were exposed to a message in which a maths test was described as stressful or challenging by an ingroup member (a student) or outgroup member (a stress disorder sufferer). Systolic blood pressure and diastolic blood pressure(DBP) and heart rate (HR) were monitored throughout a standard reactivity study. As expected, a significant interaction was found; relative to those who were told that the task was challenging, ingroup members reported more stress and had higher DBP and HR reactivity when told by an ingroup member that the maths task was stressful; task information did not have the same effect for outgroup members.
|
These results indicate that informational support is not constant but varies as a function of group membership. Finally, this recent development in stress research may prove useful for those interested in investigating the interactions between social, psychological and physiological processes underlying health disparities.
|
19,383,584 |
Is interrupted inferior vena cava a risk factor in cases of bilateral bidirectional Glenn?
|
Bilateral superior vena cava-to-pulmonary artery anastomoses are technically challenging. Bilateral superior vena cavae (SVCs) have been thought to be a risk factor for poor outcome in children needing single-ventricle palliation. The files of forty children who underwent bilateral cavopulmonary anastomoses (CPAs) were reviewed. Forty patients (31 male, 9 female) had bilateral bidirectional Glenn shunts in King Faisal Specialist Hospital and Research Center, Jeddah, in 7 years. Interrupted inferior vena cava (IIVC) was present in 8 patients. All IIVC cases featured a hypoplastic right ventricle. Twenty-four patients had a hypoplastic right ventricular morphology, and 16 patients had a hypoplastic left ventricular morphology.
|
In single-ventricle anatomy, cases of a bilateral SVC are more often associated with an IIVC than a single SVC. Patients who undergo bilateral CPAs with an IIVC have a difficult early postoperative course. We should look for IIVC and either exclude or prove IIVC in cases of bilateral SVCs. Postoperative anticoagulation therapy in children with bilateral CPAs is important but should be investigated further.
|
20,593,119 |
Do amino acids change liver growth factors gene expression in malnourished rats?
|
Glutamine and proline are metabolized the liver and may collaborate on its regeneration. Parenteral nutrition (PN) containing either glutamine or proline was given to partially hepatectomized rats. The total RNA content and growth factor gene expression in hepatic remnants was measured, to determine the effects of these amino acid supplementation on the expression of growth factors during liver regeneration. Wistar rats nourished (HN) and malnourished (HM) were hepatectomized and divided in two groups: 20 receiving PN enriched with Alanyl-Glutamine (HN-Gln and HM-Gln) and 20 PN enriched with proline+alanine (HN-Pro and HM-Pro). The control groups comprised 7 nourished (CN) and 7 malnourished (CM) rats that didn't undergo surgery. Growth factor and thymidine kinase mRNA levels were measured by RT-PCR. In nourished rats, total hepatic RNA levels were lower in the HN-Gln and HN-Pro groups (0.75 and 0.63 microg/mg tissue, respectively) than in control group (1.67 microg/mg tissue) (P<0.05). In malnourished rats, total hepatic RNA content was higher in the HM-Pro group than HN-Pro, HM-Gln, and CM (3.18 vs. 0.63, 0.93 and 1.10 microg/mg, respectively; P<0.05). Hepatocyte growth factor mRNA was more abundant in the HM-Gln group when compared to CM (0.31 vs. 0.23 arbitrary units) and also in HM-Pro in relation to HM-Gln, HN-Pro, and CM(0.46 vs. 0.33 and 0.23, respectively, P<0.05).
|
Proline or glutamine supplementation in malnourished rats improves total RNA content in the remnant hepatic tissue. Amino acids administration increased HGF gene expression after partial hepatectomy in malnourished rats, with a greater effect of proline than glutamine.
|
26,121,010 |
Is activation of IL-8 via PI3K/Akt-dependent pathway involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells?
|
Previous studies have revealed that leptin may be involved in epithelial-mesenchymal transition (EMT), a crucial initiator of cancer progression to facilitate metastatic cascade, increase tumor recurrence, and ultimately cause poor prognosis. However, the underlying mechanism remains unclear. The aim of our present study was to investigate the effect of leptin on EMT of breast cancer cells and the underlying mechanism. Our data demonstrated that leptin significantly increased the phosphorylation of STAT3, Akt, and ERK1/2, elevated the expression of IL-8, and induced breast cancer cells to undergo EMT. The effect of leptin on IL-8 could visibly abolished by the inhibitor of PI3K LY294002. In addition, leptin-induced EMT of breast cancer cells was blocked by anti-IL-8 antibodies. Examination of the expression of ObR, leptin, IL-8 and EMT-related biomarkers in patient specimens demonstrated that malignant breast carcinoma with lymph node metastases (LNM), which represents poor prognosis, expressed higher levels of ObR, leptin, IL-8 than other types of breast cancer, and displayed more obvious EMT transversion. In vivo xenograft experiment revealed that leptin signally promoted tumor growth and metastasis and increased the expressions of IL-8 and EMT-related biomarkers.
|
Our results support that leptin-induced EMT in breast cancer cells requires IL-8 activation via the PI3K/Akt signal pathway.
|
22,492,483 |
Is regional coronary endothelial function closely related to local early coronary atherosclerosis in patients with mild coronary artery disease : pilot study?
|
Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness. Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=-0.73, P=0.0008).
|
There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.
|
9,736,988 |
Is skeletal alkaline phosphatase a valid staging marker in detection of osteoblastic skeletal metastases of prostate carcinoma?
|
For patients with prostate cancer (CaP) the proof of osteoblastic bone metastases is decisive regarding the prognosis as well as the therapeutical concept. To evaluate the efficiency of skeletal alkaline phosphatase (SAP) as staging marker for bone metastases in prostate cancer, SAP was measured in CaP-patients with and without bone metastases compared with prostate-specific antigen (PSA) as the marker of choice till now. 73 patients with histological proven, but still untreated CaP were entered into the study. After staging the patients were divided into 3 groups: group I: patients with CaP and bone metastases (n = 21), group II: patients with locally advanced CaP without bone metastases (n = 26), group III: patients with clinically localized CaP without bone metastases (n = 26). Serum concentration for SAP and PSA were determined using radioimmunassay. As reference range we defined serum concentrations for SAP<19 ng/ml and for PSA<100 ng/ml. 71% of the patients with bone metastases (group I) showed elevated SAP and PSA serum concentrations. In contrast, patients without bone metastases (group II + III) have normal SAP-values (<19 ng/) and in 19% of the cases elevated PSA-values (>100 ng/ml). This resulted in a sensitivity and specificity of 71% and 100% for SAP and 71% and 81% for PSA. The positive predictive value for osteoblastic bone metastases was 100% for SAP and 60% for PSA.
|
SAP is a useful staging marker in prostate cancer and can contribute for an early detection of osteoblastic bone metastases.
|
20,482,780 |
Does treatment with apolipoprotein A-1 mimetic peptide reduce lupus-like manifestations in a murine lupus model of accelerated atherosclerosis?
|
The purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE-/-Fas-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet. Female mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment. In preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (PL, LP<0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (PL<0.05) and oxidized phospholipids (oxPLs) (PL, LP<0.005), and elevated total and vertebral bone mineral density (PL, LP<0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68+ macrophages (PLP<0.01), significantly increased mean alpha-actin stained area (PLP<0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (PL, LP<0.0005) and VCAM-1 (PL<0.0002).
|
L-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis.
|
27,178,514 |
Is ventilation tube insertion effective to the treatment of hearing impairment in pediatric patients with Cornelia de Lange syndrome?
|
Cornelia de Lange syndrome (CdLS) is a multiple developmental disorder including hearing loss. The hearing impairment in CdLS patients is not only sensorineural but also conductive hearing loss (CHL). The aim of this study was to elucidate hearing loss causes in CdLS patients and evaluate the effect of ventilation tube (v-tube) insertion in the cases of CHL. Thirty-two patients clinically diagnosed with CdLS were enrolled and analyzed with retrospective case review. Audiologic evaluations and imaging studies such as a temporal bone computed tomogram or brain magnetic resonance imaging (MRI) were performed for all patients. Hearing rehabilitation such as ventilation tube insertion, hearing aid fitting, or cochlear implantation was chosen depending on the audiological condition. Among 32 CdLS patients who underwent auditory brainstem response test, 81.2% presented hearing loss. Imaging studies showed that only middle ear lesions without inner ear anomalies were identified in 56.3%. Notably, the soft tissue lesion in middle ear was identified even in the neonatal MRI. When 7 patients were thought to have CHL due to otitis media with effusion, v-tube insertion was applied first. However, v-tube insertion rarely improved CHL postoperatively. Moreover, middle ear lesion was not fluid effusion but soft tissue lesion according to the intraoperative finding. These lesions were not eradicated even after revision surgery of v-tube insertion.
|
V-tube insertion is not effective to improve hearing or eradicate otitis media with effusion in CdLS patients.
|
25,158,300 |
Is nocturnal dry cough in the first 7 years of life associated with asthma at school age?
|
Childhood wheeze is an important, well-known risk factor for asthma, yet little is known about the contribution of nocturnal dry cough. We investigated the association of nocturnal dry cough at ages 1-7 years with doctor-diagnosed asthma at 8 years of age, both in the presence and absence of wheeze. Data of 3,252 children from the PIAMA birth cohort were studied. Parents reported the presence of nocturnal dry cough, wheeze, and doctor-diagnosed asthma in the past 12 months yearly, from birth up to the age of 8 years. Nocturnal dry cough without wheeze was significantly associated with doctor-diagnosed asthma at age 8, except for age 1 (range of Relative Risks (RR) at ages 2-7: 1.8 (age 5) - 7.1 (age 7), all P-values <0.048). As expected, wheeze without nocturnal dry cough was strongly associated with doctor-diagnosed asthma at age 8 (range of RR: 2.0 (age 1) - 22.2 (age 7), all P-values <0.003). Of interest, nocturnal dry cough with wheeze showed the strongest association with doctor-diagnosed asthma at age 8 (range of RR: 3.7 (age 1) - 26.0 (age 7), all P-values <0.001). The relative excess risk of asthma at age 8 due to interaction of nocturnal dry cough with wheeze at age 1 year was 1.8 (0.1-3.6, P < 0.01).
|
Nocturnal dry cough and wheeze in early childhood are both independently associated with asthma at school age. The presence of both nocturnal dry cough and wheeze at age 1 almost doubles the risk of asthma at age 8 compared to wheeze alone.
|
21,229,627 |
Does pelvic lymph nodes irradiation using intensity modulated radiation therapy increase rectal and bladder toxicities in patients with prostate carcinoma?
|
this study compared the radiation-related rectal (R) and bladder (B) toxicities in prostate carcinoma patients receiving additional pelvic lymph nodes (PLN) irradiation with those receiving prostate (P) and seminal vesicle (SV) irradiation only. thirty-three patients treated with intensity modulated radiation therapy (IMRT) were included. RT doses ranged between 60- 66.6 Gy to SV, 74-77.7 Gy to P and 50.4- 60 Gy to PLN. Max acute R toxicity was graded by a physician according to the RTOG side effect criteria during the period from the initiation of therapy until the end of the third month. Max late R and B toxicities were graded 3 months after the completion of RT by a physician using the RTOG GI and urogenital toxicity score and by patients using EORTC QLQ - PR25 self questionnaire separately. The effects of R and B doses and additional PLN irradiation on acute and late R and B toxicities and compatibility of patient- and physician-graded toxicity scores were investigated. RTOG GI and urogenital toxicity scores and EORTC QLQ - PR25 self questionnaire results were correlated. significant factors for acute R toxicity were: max R; R volume receiving ≥ 68 Gy; and PLN irradiation. PLN irradiation was marginally significant for late R toxicity; the mean B dose was a significant factor for late B toxicity.
|
the results of this study suggest that although PLN irradiation increased acute R toxicity, it has no effect on late R and B toxicity. Patient- and physician-evaluated late R and B toxicity scores were concordant.
|
19,940,724 |
Is outcome after surgical treatment for lumbar spinal stenosis : the lumbar extension test a predictive factor?
|
A prospective clinical study. To investigate the predictive value of the lumbar extension test for outcome after surgical treatment of lumbar spinal stenosis (LSS). Studies have indicated that aggravation of the symptoms from LSS by extension of the lumbar spine has predictive value for the outcome after decompression. The aim of this study was to investigate this theory in a larger group of patients. One hundred forty-six consecutive patients surgically treated for LSS were included in the study. The clinical condition was recorded before surgery and at 3, 6, 12, and 24 months after surgery using 3 different scoring systems: Swiss Spinal Stenosis Questionnaire, Neurogenic Claudication Outcome Score, and Oswestry Disability Index. The group of patients with preoperative aggravation of the symptoms by the lumbar extension test, (positive extension test), was compared with the group of patients without aggravation by the test, (negative extension test). Before surgery, patients with a positive extension test scored significantly worse on all disability scoring systems than patients with a negative test. However, the extension test itself had no prognostic value for the overall outcome after lumbar decompression. Using regression models with the 2-year Oswestry Disability Index as dependent variable, only before surgery self-reported health and age were found to have prognostic significance.
|
The lumbar extension test has no predictive value for the outcome after surgical treatment of LSS.
|
25,370,466 |
Does habitual Myofibrillar Protein Synthesis be Normal in Patients with Upper GI Cancer Cachexia?
|
Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls. An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography-pyrolysis-isotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown. Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03).
|
Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.
|
16,796,604 |
Does tGF-beta1 generate a specific multicomponent extracellular matrix in human coronary SMC?
|
Transforming growth factor (TGF-beta(1)) is postulated to play an important role in maintaining the structure and function of arterial tissue and protection against development of arteriosclerosis. The TGF-beta(1)-induced production of a stable extra-cellular matrix-rich plaque phenotype is suggested to be part of the protection against a switch to an unstable rupture-prone arteriosclerotic plaque. This study addresses the question of whether the expression profile and the type of extra-cellular matrix (ECM) generated by TGF-beta(1) stimulation have the structural feature of a fibril-rich stable matrix. Seventeen genes codings for ECM components of human coronary smooth muscle cells (SMCs) after a 24-h stimulation by TGF-beta(1) have been analyzed. Real-time RT-PCR was used to quantify the mRNA of genes under investigation. It was found that after TGF-beta(1) stimulation (a) the up-regulation of COL1A1-specific mRNA was associated with increased [(3)H]proline incorporation into the alpha-1 and -2 chains of collagen type I, (b) the up-regulation of biglycan- and syndecan-1-specific mRNA corresponded to an increased [(35)S]sulphate and [4,5-(3)H]leucine incorporation into the biglycan molecule and to an increase of syndecan-1 protein, (c) the up-regulated FGF-2 gene accounted predominantly for the ECM-bound subfraction of FGF-2-protein and (d) fibronectin and thrombospondin exhibited a significantly higher mRNA level. In contrast collagen XIV, a minor collagen type, and the proteoglycan decorin were down-regulated. The down-regulated decorin changed its structure by elongation and reduced GlcA to IdoA epimerization of the dermatan sulphate side-chain as judged by [(35)S]sulphate metabolic labelling experiments. No significant changes in response to TGF-beta(1) were observed for the collagen types III, VI and XVI, for versican, perlecan and the syndecans-2 and -4.
|
It was concluded from the data that the TGF-beta(1)-induced formation of a highly specific multicomponent extra-cellular matrix on coronary arterial SMCs could provide in vivo mechanical strength to the neointima in arteriosclerotic lesions and to the fibrous cap overlying the lipid core.
|
18,085,737 |
Does incorporation of aids and devices make a difference in the score of the health assessment questionnaire-disability index?
|
The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a commonly used musculoskeletal-targeted measure in systemic sclerosis (SSc). We assessed if HAQ-DI scores are different when calculated with and without aids/devices, and if apparent responsiveness changes when scored in these 2 ways. We used data from a placebo-controlled clinical trial in diffuse SSc. Baseline HAQ-DI total score was calculated with and without aids/devices and compared using Student's t-test. We also classified the HAQ-DI scores into no-to-mild disability (0.00-1.00), moderate disability (1.01-2.00), and severe disability (2.01-3.00). Responsiveness to change was evaluated using the effect size (ES). The mean (SD) baseline HAQ-DI score was 1.33 (0.68) with aids/devices compared to HAQ-DI score 1.16 (0.70) without aids/devices (p = 0.03). When the baseline HAQ-DI score was categorized into no-to-mild, moderate, and severe disability, the proportion of patients in the no-to-mild disability (29% with aids/devices vs 44% without aids/devices) and moderate disability (59% with aids/devices vs 45% without aids/devices) groups were statistically different (p<0.001). The ES was similar between the 2 groups (ES = 0.01 and 0.02 with and without aids/devices).
|
This analysis suggests a shift from no-to-mild disability to moderate disability when aids/devices are incorporated in total HAQ-DI score. Future clinical trials in SSc should explicitly state whether HAQ-DI score was calculated using aids/devices.
|
21,039,404 |
Does deregulation of PERK in the autoimmune disease pemphigus vulgaris occur via IgG-independent mechanisms?
|
Serum and IgG isolated from patients with the autoimmune blistering disease pemphigus vulgaris (PV) trigger complex intracellular pathways in keratinocytes, including alterations of the cell cycle and metabolism, which ultimately lead to cell-cell detachment (acantholysis). We have shown previously that one of the earliest pathogenic events in PV is the activation of protein kinases, including the PKR-like endoplasmic reticulum (ER) kinase PERK. In the present study we investigated in more detail the role of PERK in the pathogenesis of PV. PERK levels were assessed by Western blotting and in-cell enzyme-linked immunosorbent assay, and PERK expression was silenced by siRNA technology. The effects of PV sera/IgG on keratinocyte cultures were investigated by flow cytometry, MTT and adhesion assays. We show that PERK is activated in keratinocytes exposed to PV serum, as demonstrated by an increase in phosphorylated PERK levels and phosphorylation of eIF2α. Decreased expression of PERK by siRNA reduced the effects of PV serum on the cell cycle and keratinocyte viability, two key events in PV pathophysiology. As impairment of metabolic activity in PV is partially due to non-IgG serum factors, we then investigated the activation of PERK in keratinocytes incubated with whole PV serum, purified PV IgG and IgG-depleted PV serum. The data demonstrated that PV sera depleted of IgG, but not PV IgG, triggered PERK phosphorylation and this correlated with a marked reduction of metabolic activity in keratinocytes exposed to IgG-free serum. Knockdown of PERK by siRNA abrogated the changes in the cell cycle and apoptosis induced by IgG-depleted PV serum. Finally, the reduction of metabolic activity observed in keratinocytes exposed to IgG-depleted PV serum was almost absent in PERK-deficient cells.
|
Taken together, the results demonstrate that activation of PERK participates in the reduction of metabolic activity and cell viability seen in PV and that this phenomenon depends on non-IgG factors. PERK activation may represent a novel signalling mechanism linking ER stress and acantholysis in PV.
|
25,764,969 |
Do bacillus amyloliquefaciens strain 32a as a source of lipopeptides for biocontrol of Agrobacterium tumefaciens strains?
|
A Bacillus amyloliquefaciens strain, designated 32a, was used to identify new compounds active against Agrobacterium tumefaciens and to evaluate their efficiency to control crown gall on carrot discs. Based on PCR-assays, four gene clusters were shown to direct the synthesis of the cyclic lipopeptides surfactin, iturin A, bacillomycin D and fengycin. Mass spectrometry analysis of culture supernatant led to the identification of these secondary metabolites, except bacillomycin, with heterogeneous mixture of homologues. Antimicrobial assays using lipopeptides-enriched extract showed a strong inhibitory activity against several bacterial and fungal strains, including Ag. tumefaciens. Biological control assays on carrot discs using both 32a spores and extract resulted in significant protection against crown gall disease, similar to that provided by the reference antagonistic strain Agrobacterium rhizogenes K1026.
|
In contrast to all active compounds against Ag. tumefaciens that are of proteinaceous nature, this work enables for the first time to correlate the strong protective effect of B. amyloliquefaciens strain 32a towards crown gall disease with the production of a mixture of lipopeptides.
|
26,397,229 |
Can automation in radiotherapy reduce costs?
|
Computerized automation is likely to play an increasingly important role in radiotherapy. The objective of this study was to report the results of the first part of a program to implement a model for economical evaluation based on micro-costing method. To test the efficacy of the model, the financial impact of the introduction of an automation tool was estimated. A single- and multi-center validation of the model by a prospective collection of data is planned as the second step of the program. The model was implemented by using an interactive spreadsheet (Microsoft Excel, 2010). The variables to be included were identified across three components: productivity, staff, and equipment. To calculate staff requirements, the workflow of Gemelli ART center was mapped out and relevant workload measures were defined. Profit and loss, productivity and staffing were identified as significant outcomes. Results were presented in terms of earnings before interest and taxes (EBIT). Three different scenarios were hypothesized: baseline situation at Gemelli ART (scenario 1); reduction by 2 minutes of the average duration of treatment fractions (scenario 2); and increased incidence of advanced treatment modalities (scenario 3). By using the model, predicted EBIT values for each scenario were calculated across a period of eight years (from 2015 to 2022). For both scenarios 2 and 3 costs are expected to slightly increase as compared to baseline situation that is particularly due to a little increase in clinical personnel costs. However, in both cases EBIT values are more favorable than baseline situation (EBIT values: scenario 1, 27%, scenario 2, 30%, scenario 3, 28% of revenues).
|
A model based on a micro-costing method was able to estimate the financial consequences of the introduction of an automation tool in our radiotherapy department. A prospective collection of data at Gemelli ART and in a consortium of centers is currently under way to prospectively validate the model.
|
22,396,501 |
Does statin inhibit hypoxia-induced endothelin-1 via accelerated degradation of HIF-1α in vascular smooth muscle cells?
|
Endothelin-1 (ET-1) contributes to the pathogenesis of cardiovascular diseases with multiple properties such as vasoconstriction. Human ET-1 gene expression is up-regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1) through hypoxia response element (HRE). Although previous studies suggested that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) alter HIF-1-related gene expression, it remained unclear whether statins modulate HIF-1-mediated ET-1 expression. Therefore, we investigated the effect of fluvastatin on hypoxia-induced human ET-1 expression in vascular smooth muscle cells (VSMC). Hypoxia (1% O(2)), compared with the normoxic condition (21% O(2)), significantly induced the expression of preproET-1 mRNA, ET-1 protein, and ET-1 secretion in VSMC. Hypoxia induced a 2.3-fold increase in HRE-dependent ET-1 reporter gene activation. Under concentrations of 1 µmol/L or greater, fluvastatin attenuated the hypoxia-induced ET-1 gene expression through the accelerated ubiquitin/proteasome-dependent degradation of HIF-1α, thus consequently attenuating HIF-1α binding to the HRE of the ET-1 gene. These inhibitory effects of fluvastatin were cancelled by concomitant treatment with mevalonate, farnesyl pyrophosphate, or geranylgeranyl pyrophosphate, but not squalene.
|
The present study suggests that fluvastatin attenuates HIF-1-dependent ET-1 gene expression in conjunction with the stimulation of HIF-1α ubiquitin/proteasome-dependent degradation via isoprenoid-dependent mechanisms.
|
26,315,406 |
Does rho-Kinase Inhibition During Early Cardiac Development cause Arrhythmogenic Right Ventricular Cardiomyopathy in Mice?
|
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty changes of the right ventricle, ventricular arrhythmias, and sudden death. Though ARVC is currently regarded as a disease of the desmosome, desmosomal gene mutations have been identified only in half of ARVC patients, suggesting the involvement of other associated mechanisms. Rho-kinase signaling is involved in the regulation of intracellular transport and organizes cytoskeletal filaments, which supports desmosomal protein complex at the myocardial cell-cell junctions. Here, we explored whether inhibition of Rho-kinase signaling is involved in the pathogenesis of ARVC. Using 2 novel mouse models with SM22α- or αMHC-restricted overexpression of dominant-negative Rho-kinase, we show that mice with Rho-kinase inhibition in the developing heart (SM22α-restricted) spontaneously develop cardiac dilatation and dysfunction, myocardial fibrofatty changes, and ventricular arrhythmias, resulting in premature sudden death, phenotypes fulfilling the criteria of ARVC in humans. Rho-kinase inhibition in the developing heart results in the development of ARVC phenotypes in dominant-negative Rho-kinase mice through 3 mechanisms: (1) reduction of cardiac cell proliferation and ventricular wall thickness, (2) stimulation of the expression of the proadipogenic noncanonical Wnt ligand, Wnt5b, and the major adipogenic transcription factor, PPARγ (peroxisome proliferator activated receptor-γ), and inhibition of Wnt/β-catenin signaling, and (3) development of desmosomal abnormalities. These mechanisms lead to the development of cardiac dilatation and dysfunction, myocardial fibrofatty changes, and ventricular arrhythmias, ultimately resulting in sudden premature death in this ARVC mouse model.
|
This study demonstrates a novel crucial role of Rho-kinase inhibition during cardiac development in the pathogenesis of ARVC in mice.
|
21,786,060 |
Is depression associated with prolonged and complicated recovery following colorectal surgery?
|
There are little data regarding the impact of depression on outcomes after gastrointestinal surgery. We hypothesize that depression would be associated with prolonged hospital stay and changes in discharge disposition for patients undergoing colon and rectal surgery. We identified 292,191 patients undergoing colon and rectal surgery using the 2008 Nationwide Inpatient Sample. We used multivariate regression to evaluate the effect of depression on length of stay and discharge disposition. A preoperative diagnosis of depression was present in 20,039 (6.9%) patients. Mean length of stay for those with depression (10.4 days, 95% confidence interval (CI) 10.04-10.76) was significantly longer than for patients without depression (9.64 days, 95% CI 9.48-9.81). After adjusting for cofounders, depression still predicted an increase in length of stay. Additionally, depressed patients were less likely to resume normal function at discharge, as 40% required either home health or time in a skilled facility following discharge from the acute care hospital.
|
Among patients undergoing colorectal surgery, depression is associated with a significantly prolonged hospital stay and higher likelihood of requiring skilled nursing assistance after discharge. Further research into the mechanism underlying these differences and potential treatment strategies among depressed patients is warranted.
|
22,943,554 |
Does impact of C-reactive protein test result on evidence-based decision-making in cases of bacterial infection?
|
C-reactive protein (CRP) is widely used to detect bacterial infection in children. We investigated the impact of CRP test results on decision-making and summarized the evidence base (EB) of CRP testing. We collected information from the hospital records of 91 neonates with suspected sepsis and of 152 febrile children with suspected infection on the number of ordered CRP tests, the number of EB-CRP tests, and the impact of the test results on decision-making. CRP diagnostic accuracy studies focusing on pediatric infections were reviewed critically. The main outcomes were the proportion of CRP tests that were EB and the proportion of tests that affected decision-making. A secondary outcome was the overall one-year expenditure on CRP testing. The current EB for CRP testing in pediatric infections is weak and suggests that CRP is of low diagnostic value. Approximately 54.8% of tests performed for suspected neonatal sepsis and 28% of tests performed for other infections were EB; however, the results of only 12.9% of neonatal sepsis tests and of 29.9% of tests on children with other infections informed decision-making. The one-year overall cost for CRP testing and related health care was $26,715.9.
|
The routine ordering of CRP for children with infections is based on weak evidence. The impact of the CRP test results on decision-making is rather small, and CRP ordering may contribute to unnecessary health care expenditures. Better quality research is needed to definitively determine the diagnostic accuracy of CRP levels in children with infections.
|
21,961,997 |
Is immune risk phenotype associated with nosocomial lung infections in elderly in-patients?
|
Nosocomial infections are extremely common in the elderly and may be related to ageing of the immune system. The Immune Risk Phenotype (IRP), which predicts shorter survival in elderly patients, has not been evaluated as a possible risk factor for nosocomial infection. Our aim was to assess the prevalence of nosocomial infections in elderly in-patients and to investigate potential relationships between nosocomial infections and the immunophenotype, including IRP parameters. We included 252 consecutive in-patients aged 70 years or over (mean age, 85 ± 6.2 years), between 2006 and 2008. Among them, 97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95% confidence interval, 32.5-44.5). The main infection sites were the respiratory tract (21%) and urinary tract (17.1%) When we compared immunological parameters including cell counts determined by flow cytometry in the groups with and without nosocomial infections, we found that the group with nosocomial infections had significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell counts and higher counts of memory CD8 T-cells with a significant increase in CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246 patients) nor presence of the IRP was associated with nosocomial infections. However, nosocomial pneumonia was significantly more common among IRP-positive patients than IRP-negative patients (17/60 versus 28/180; p = 0.036).
|
Immunological parameters that are easy to determine in everyday practice and known to be associated with immune system ageing and shorter survival in the elderly are also associated with an elevated risk of nosocomial pneumonia in the relatively short term.
|
16,505,022 |
Are mapping collagen organization in the human cornea : left and right eyes structurally distinct?
|
Aspects of the biomechanics and surface topography of fellow human corneas are known to exhibit midline symmetry, but the structural basis of these observations is poorly understood. The mechanical performance of the cornea is strongly influenced by the organization of stromal collagen fibrils. The present study was designed to examine and compare the organization of collagen fibrils in the corneal stroma of left and right eyes. Wide-angle x-ray scattering was used to map in detail the orientation and distribution of fibrillar collagen across the cornea, limbus, and adjacent sclera of three normal human eyes, including a fellow pair, and the central 9-mm corneal region of a further four eyes. Fibrillar collagen in the human cornea and limbus is arranged anisotropically, and in a highly specific manner. Left and right corneas are structurally distinct. In general, the mass distribution of preferentially aligned fibrils in the cornea appears to exhibit a degree of midline symmetry between left and right eyes.
|
Structural information, such as that presented herein, will enable a better understanding of corneal biomechanics and shape. Midline symmetry in the distribution of aligned, mechanically reinforcing collagen fibrils between left and right eyes may relate to the biomechanical and topographical enantiomorphism reported in the literature.
|
27,863,473 |
Is aNLN a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer?
|
Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. High nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1.
|
ANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.
|
25,276,151 |
Does contractile reserve assessed by dobutamine test identify super-responders to cardiac resynchronization therapy?
|
In this study, we sought to determine whether myocardial contractile reserve (CR) assessed by dobutamine stress echocardiography (DSE) can identify patients who experience nearly complete normalization of left ventricular (LV) function after the implantation of a cardiac resynchronization therapy (CRT) pacemaker. The study group consisted of 55 consecutive patients with non-ischemic dilated cardiomyopathy, LV ejection fraction (LVEF) < 35%, and prolonged QRS complex duration, who were scheduled for CRT pacemaker implantation. The DSE (20 µg/kg/min) was performed in all patients. The CR assessment was based on a change in the wall motion score index (ΔWMSI) and ΔLVEF during DSE. Super-response was defined as an increase in LVEF to > 50% and reduction in left ventricular end-systolic dimension to < 40 mm 12 months following the CRT implantation. A total of 7 patients (12.7%) were identified as super-responders to CRT. When compared to non-super-responders, these patients had significantly higher values of the dobutamine-induced change in ΔWMSI (1.031 ±0.120 vs. 0.49 ±0.371, p < 0.01), and ΔEF (17.9 ±2.2 vs. 8.8 ±6.2, p < 0.01). Receiver operating characteristic analysis showed that dobutamine-induced changes in ΔWMSI ≥ 0.7 and ≥ 14% for ΔEF are the best discriminators for a super-response. Patients with ΔWMSI ≥ 0.7 and ΔEF ≥ 14% are significantly less often hospitalized (p < 0.01) for worsening of heart failure during 28.5 ±3.0 months of the follow-up.
|
Contractile reserve assessed by DSE can identify patients with dilated cardiomyopathy who are likely to experience near normalization of LV function following CRT.
|
7,777,735 |
Do out-of-office laboratory tests affect diagnoses in general practice?
|
To find out whether the GP diagnosis changed by out-of-office laboratory test results and whether his diagnosis became more certain. Descriptive study. Dutch survey of morbidity and interventions in general practice: stratified random sample of 161 GPs with a total list of 335,000 patients. 2,081 episodes of illness with at least one consultation with clinical chemistry, haematology, or serology tests and at least one follow-up consultation. Change in ICPC component or chapter between the consultation in which a laboratory test was ordered and the follow up contact; change in exact ICPC code in cases with important diseases (infectious diseases, haematological disorders, endocrine abnormalities, auto-immune processes and malignancies (n = 330)); change in certainty of a diagnosis and change in somatic/psychosocial orientation. After laboratory tests done in the first consultation the ICPC component changed in 46% of the diagnoses. Of the diagnoses made in first consultations without laboratory tests 41% changed in the follow up consultation. The diagnosis after laboratory tests was the same as before in 51% of the consultations with important diseases. Certainty about a diagnosis increased significantly after laboratory tests (p<0.001). An abnormal laboratory result did not affect the clinical certainty of the general practitioner or the percentage of altered diagnoses.
|
The usefulness of tests should be assessed not only in terms of the number of diagnoses changed or of the percentage of abnormal results, but also in terms of the changed certainty concerning a diagnosis.
|
9,794,564 |
Does long-term treatment of renal anaemia with recombinant erythropoietin influence oxidative stress in haemodialysed patients?
|
Patients with end-stage renal failure undergoing haemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) were demonstrated in plasma of uraemic patients, indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients. MDA and 4-hydroxynonenal (HNE) were measured in three groups of patients undergoing HD: group I comprised eight patients with a blood haemoglobin (Hb)<10 g/dl (mean Hb = 8.1+/-1.3 g/dl), and group II were eight patients with a Hb>10 g/dl (mean Hb=12.4+/-1.9g/dl); none of these 16 patients had been treated with human recombinant erythropoietin (rHuEpo). Group III comprised 27 patients with a mean Hb of 10.5+/-1.6 g/dl after long-term rHuEpo treatment. Mean plasma concentrations of both MDA and HNE were significantly higher (P<0.0001) in all 43 HD patients than in 20 healthy controls (MDA 2.85+/-0.25 vs 0.37+/-0.03 microM, HNE 0.32+/-0.03 vs 0.10+/-0.01 microM). Comparing the three groups, it was shown that HD patients with a Hb<10 g/dl had significantly higher plasma levels of LPO products (MDA 3.81+/-0.86 microM, HNE 0.45+/-0.07 microM) than HD patients with a Hb>10g/dl (MDA 2.77+/-0.58 UM, HNE 0.25+/-0.05 microM), and than HD patients treated with rHuEpo (MDA 2.50+/-0.12 microM, HNE 0.29+/-0.03 microM). Furthermore, an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen (r=0.62, P<0.0001).
|
Radical generation in HD patients might be caused in part by renal anemia itself. Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration.
|
9,639,376 |
Does inhibition of neutral endopeptidase cause vasoconstriction of human resistance vessels in vivo?
|
Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides, angiotensin II, and endothelin-1. Systemic inhibition of NEP does not consistently lower blood pressure, even though it increases natriuretic peptide concentrations and causes natriuresis and diuresis. We therefore investigated the direct effects of local inhibition of NEP on forearm resistance vessel tone. Four separate studies were performed, each with 90-minute drug infusions. In the first study, 10 healthy subjects received a brachial artery infusion of the NEP inhibitor candoxatrilat (125 nmol/min), which caused a slowly progressive forearm vasoconstriction (12+/-2%; P=0.001). In a second two-phase study, 6 healthy subjects received, 4 hours after enalapril (20 mg) or placebo, an intra-arterial infusion of the NEP inhibitor thiorphan (30 nmol/min). Thiorphan caused similar degrees of local forearm vasoconstriction (P=0.6) after pretreatment with both placebo (13+/-1%, P=0.006) and enalapril (17+/-6%, P=0.05). In a third three-phase study, 8 healthy subjects received intra-arterial thiorphan (30 nmol/min), the endothelin ETA antagonist BQ-123 (100 nmol/min), and both combined. Thiorphan caused local forearm vasoconstriction (13+/-1%, P=0.0001); BQ-123 caused local vasodilatation (33+/-3%, P=0.0001). Combined thiorphan and BQ-123 caused vasodilatation (32+/-1%, P=0.0001) similar to BQ-123 alone (P=0.98). In a fourth study, 6 hypertensive patients (blood pressure >160/100 mm Hg) received intra-arterial thiorphan (30 nmol/min). Thiorphan caused a slowly progressive forearm vasoconstriction (10+/-2%, P=0.0001).
|
Inhibition of local NEP causes vasoconstriction in forearm resistance vessels of both healthy volunteers and patients with hypertension. The lack of effect of ACE inhibition on the vasoconstriction produced by thiorphan and its absence during concomitant ETA receptor blockade suggest that it is mediated by endothelin-1 and not angiotensin II. These findings may help to explain the failure of systemic NEP inhibition to lower blood pressure.
|
23,799,974 |
Does granulocyte-macrophage colony stimulating factor ( GM-CSF ) enhance cumulus cell expansion in bovine oocytes?
|
The objectives of the study were to characterize the expression of the α- and β-subunits of granulocyte-macrophage colony stimulating factor (GM-CSF) receptor in bovine cumulus cells and oocytes and to determine the effect of exogenous GM-CSF on cumulus cells expansion, oocyte maturation, IGF-2 transcript expression and subsequent competence for embryonic development. Cumulus-oocyte complexes (COC) were obtained by aspirating follicles 3- to 8-mm in diameter with an 18 G needle connected to a vacuum pump at -50 mmHg. Samples of cumulus cells and oocytes were used to detect GM- CSF receptor by immunofluorescence. A dose-response experiment was performed to estimate the effect of GM-CSF on cumulus cell expansion and nuclear/cytoplasmic maturation. Also, the effect of GM-CSF on IGF-2 expression was evaluated in oocytes and cumulus cells after in vitro maturation by Q-PCR. Finally, a batch of COC was randomly assigned to in vitro maturation media consisting of: 1) synthetic oviductal fluid (SOF, n = 212); 2) synthetic oviductal fluid supplemented with 100 ng/ml of GM-CSF (SOF + GM-CSF, n = 224) or 3) tissue culture medium (TCM 199, n = 216) and then subsequently in vitro fertilized and cultured for 9 days. Immunoreactivity for both α and β GM-CSF receptors was localized in the cytoplasm of both cumulus cells and oocytes. Oocytes in vitro matured either with 10 or 100 ng/ml of GM-CSF presented a higher (P < 0.05) cumulus cells expansion than that of the control group (0 ng/ml of GM-CSF). GM-CSF did not affect the proportion of oocytes in metaphase II, cortical granules dispersion and IGF-2 expression. COC exposed to 100 ng/ml of GM-CSF during maturation did not display significant differences in terms of embryo cleavage rate (50.4% vs. 57.5%), blastocyst development at day 7 (31.9% vs. 28.7%) and at day 9 (17.4% vs. 17.9%) compared to untreated control (SOF alone, P = 0.2).
|
GM-CSF enhanced cumulus cell expansion of in vitro matured bovine COC. However, GM-CSF did not increase oocyte nuclear or cytoplasmic maturation rates, IGF-2 expression or subsequent embryonic development.
|
11,987,079 |
Does intraoperative ultrasound reduce ECMO catheter malposition requiring surgical correction?
|
One hundred ninety-three cannulation procedures for extracorporeal membrane oxygenation (ECMO) have been performed at the authors' institution from 1994 to now. Before 1996, their practice had been to position these catheters exclusively by clinical assessment and chest radiograph. Since then, the authors have utilized intraoperative ultrasound guidance during cannulation procedures to confirm proper tip position. This retrospective analysis was undertaken to establish whether this practice has reduced the rate of surgical repositioning of ECMO catheters in these patients. A retrospective chart review was performed for all infants who underwent ECMO cannulation procedures at the authors' institution. Numbers of infants requiring surgery to readjust ECMO catheter position were totaled. Cases were categorized according to the presence or absence of intraoperative ultrasound scan. Statistical significance was determined using X(2) analysis, Student's t test, or analysis of variance where appropriate. There were 193 ECMO cannulations performed. Of the 101 procedures done without ultrasound scan, 18 necessitated surgical repositioning. In contrast, only 3 of the 92 catheters placed with ultrasound assistance required reoperation. This represents a reduction the rate of repositioning from 17.8% to 3.3% of cannulations (P =.003).
|
Based on these findings, the authors advocate the use of intraoperative ultrasound imaging to optimize the position of ECMO catheters. This high rate of initial success helps avoid the potential morbidity of ECMO circuit malfunction, repeat neck dissection, and catheter manipulation in these critically ill, anticoagulated patients.
|
27,297,427 |
Does dietary supplementation of curcumin alleviate NF-κB-dependent skeletal muscle wasting in rat?
|
Activation of the nuclear factor-kappa b (NF-κB) signaling results in releasing of a variety of inflammatory cytokines that can induce skeletal muscle wasting (MW) in mammals. Curcumin is a natural product from spice turmeric that can block biological events in which NF-κB plays a critical role. The present study was conducted to evaluate the beneficial effects of curcumin on the NF-κB-dependent MW in rats. The MW rats were induced by lipopolysaccharide (LPS) injection and rats were fed 15 g curcumin per kg diet for 16 d. LPS not only decreased the growth performance of rat, but significantly elevated its serum IL-1 concentration and muscle proteolysis rate. Interestingly, curcumin significantly prevented the muscle proteolysis rate and down-regulated expression levels of two critical muscle-specific ubiquitin ligases (Atrogin-1 and MuRF-1). When muscles from MW rats were incubated with curcumin in vitro, the calpain-, cathepsin L-, and proteasome-dependent muscle proteolysis were significantly decreased. Moreover, the nuclear NF-κB/p65 protein abundance were also decreased by curcumin.
|
The results not only suggest a molecular mechanism by which curcumin modulates the inflammatory responses, but also offer a feasible avenue to ameliorate the NF-κB-dependent muscle proteolysis.
|
12,411,811 |
Does brachial plexus nerve block exhibit prolonged duration in the elderly?
|
Upper limb trauma occurs frequently in elderly patients for whom peripheral nerve blocks are often preferred for anesthesia. The characteristics of such regional blocks have, however, never been described in an elderly population. Therefore, the authors assessed prospectively the onset and duration of upper extremity peripheral nerve block (the mid-humeral block) in elderly and young patients undergoing emergency upper extremity surgery. Consecutive patients aged > 70 yr or < 70 yr received a mid-humeral block with a small volume of ropivacaine, 0.75%. Five milliliters was injected onto each of the musculocutaneous, radial, ulnar, and median nerves. Time to complete sensory and motor block and durations of complete sensory and motor block were assessed. Results are shown as median and its 95% confidence interval. Median ages were 77 yr (95% CI, 72-81 yr) and 39 yr (95% CI, 27-46 yr) in the two groups. Both groups had similar times to complete sensory blockade. The elderly group had longer durations of complete sensory (390 min [range, 280-435 min] vs.150 min [range, 105-160 min]; P< 0.05) and motor (357 min [range, 270-475 min] vs. 150 min [range, 90-210 min]; P< 0.05) blockade. Duration of complete sensory block was significantly correlated with age (rho = 0.56; P< 0.05).
|
Age is a major determinant of duration of complete motor and sensory blockade with peripheral nerve block, perhaps reflecting increased sensitivity to conduction failure from local anesthetic agents in peripheral nerves in the elderly population.
|
23,422,796 |
Do propofol and thiopental suppress amyloid fibril formation and GM1 ganglioside expression through the γ-aminobutyric acid A receptor?
|
The incidence of Alzheimer disease may increase after surgical interventions. Amyloid β-protein (Aβ) fibrillogenesis, which is closely related to Alzheimer disease, is reportedly accelerated by exposure to anesthetics. However, the effects of GM1 ganglioside (GM1) on Αβ fibrillogenesis have not yet been reported. The current study was designed to examine whether the anesthetics propofol and thiopental are associated with Αβ assembly and GM1 expression on the neuronal cell surface. PC12N cells and cultured neuronal cells were treated with propofol or thiopental, and GM1 expression in treated and untreated cells was determined by the specific binding of horseradish peroxidase-conjugated cholera toxin subunit B (n = 5). The effects of an inhibitor of the γ-aminobutyric acid A receptor was also examined (n= 5). In addition, the effects of the anesthetics on GM1 liposome-induced Αβ assembly were investigated (n = 5). Finally, the neurotoxicity of the assembled Αβ fibrils was studied by the lactate dehydrogenase release assay (n = 6). Propofol (31.2 ± 4.7%) and thiopental (34.6 ± 10.5%) decreased GM1 expression on the cell surface through the γ-aminobutyric acid A receptor. The anesthetics inhibited Αβ fibril formation from soluble Αβ in cultured neurons. Moreover, propofol and thiopental suppressed GM1-induced fibril formation in a cell-free system (propofol, 75.8 ± 1.9%; thiopental, 83.6 ± 1.9%) and reduced the neurotoxicity of a mixture containing Aβ and GM1 liposomes (propofol, 35.3 ± 16.4%; thiopental, 21.3 ± 11.6%).
|
Propofol and thiopental have direct and indirect inhibitory effects on Αβ fibrillogenesis.
|
15,513,313 |
Does cardioprotection afforded by ischemic preconditioning interfere with chronic beta-blocker treatment?
|
The efficacy of ischemic preconditioning of the heart has remained controversial. We investigated whether chronic treatment with beta-blockers affects the ischemic preconditioning in the isolated rat heart model. Wistar rats were treated with propranolol (50 mg/kg/day, p.o.) (PRL), with nipradilol (10 mg/kg/day, p.o.) (NPL), or with vehicle, for 4 weeks. Isolated rat hearts were divided into global ischemia hearts (GI, PRL and NPL, each n=6) and ischemic preconditioned hearts (IP, PRL+IP and NPL+IP, each n=6). Significant differences in left ventricular pressure were observed between the PRL and PRL+IP, and between the NPL and NPL+IP groups. In the NPL group, significant amelioration and preservation of left ventricular peak pressure, coronary flow, reduction of infarct size, and NOx preservation were observed. Lipid peroxidation in the NPL group was significantly reduced before and after global ischemia compared to the GI group.
|
The effect of ischemic preconditioning was abolished in the hearts of rats following oral treatment of propranolol or nipradilol. However, the administration of nipradilol protected the ischemic and reperfused myocardium, partly due to the prevention of lipid peroxide formation.
|
16,491,218 |
Does intraluminal injection of short chain fatty acids diminish intestinal mucosa injury in experimental ischemia-reperfusion?
|
Investigated the effect of intraluminal short-chain fatty acids (SCFA) on the intestinal mucosa in the presence of ischemia-reperfusion injury (IRI). Six blind sacs of the small bowel (3 at the jejunum and 3 at the ileum) were created in ten Wistar rats. The lateral sacs of both bowel regions were subjected to IRI (15/15 minutes) while the medial sacs were let free to receive blood supply. In the lateral sacs, it was injected either a solution containing SCFA (butyrate, propionate and acetate) or pure saline at the bowel lumen. No fluid was injected in the medial sacs. Both at the jejunum and at the ileum the score of the mucosal injury was higher in saline than in control sacs. SCFA treated sacs showed lesser score at the ileum (p = 0.03) but were not significantly different at the jejunum (p = 0.83) when compared with saline sacs. It was found a significant greater number of neutrophils (p < 0.01) in the sacs treated with saline than in the other two sacs in both regions.
|
SCFA protect the distal small bowel mucosa and diminishes infiltration of neutrophils to the gut lamina propria in IRI.
|
19,284,555 |
Does delta-Catenin promote prostate cancer cell growth and progression by altering cell cycle and survival gene profiles?
|
delta-Catenin is a unique member of beta-catenin/armadillo domain superfamily proteins and its primary expression is restricted to the brain. However, delta-catenin is upregulated in human prostatic adenocarcinomas, although the effects of delta-catenin overexpression in prostate cancer are unclear. We hypothesized that delta-catenin plays a direct role in prostate cancer progression by altering gene profiles of cell cycle regulation and cell survival. We employed gene transfection and small interfering RNA to demonstrate that increased delta-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. delta-Catenin promoted prostate cancer cell colony formation in soft agar as well as tumor xenograft growth in nude mice. Deletion of either the amino-terminal or carboxyl-terminal sequences outside the armadillo domains abolished the tumor promoting effects of delta-catenin. Quantitative RT2 Profiler PCR Arrays demonstrated gene alterations involved in cell cycle and survival regulation. delta-Catenin overexpression upregulated cyclin D1 and cdc34, increased phosphorylated histone-H3, and promoted the entry of mitosis. In addition, delta-catenin overexpression resulted in increased expression of cell survival genes Bcl-2 and survivin while reducing the cell cycle inhibitor p21Cip1.
|
Taken together, our studies suggest that at least one consequence of an increased expression of delta-catenin in human prostate cancer is the alteration of cell cycle and survival gene profiles, thereby promoting tumor progression.
|
18,283,592 |
Is anti-cancer effect of bio-reductive drug beta-lapachon enhanced by activating NQO1 with heat shock?
|
Bio-reduction/activation of anti-cancer drug beta-lapachone (beta-lap) is mediated by NAD(P)H: Quinone oxidoreductase (NQO1). We investigated the feasibility of using mild temperature hyperthermia to increase the anti-cancer effect of beta-lap by up-regulating NQO1 expression. NQO1 expression in FSaII fibrosarcoma of C3H mice and A549 human lung cancer cells was evaluated with Western blot analysis and immunostaining of cells at different times after water-bath heating. Clonogenic cell survival method was used to determine the sensitivity of cells to heating, beta-lap, and in combination. The growth of FSaII tumors in the right hind legs of C3H mice was studied after heating the tumors at 42 degrees C for 1 h with water bath, an i.p. injection of beta-lap to host mice or an i.p. injection of beta-lap 24 h after heating the tumors. Heating at 42 degrees C for 1 h significantly increased the expression of NQO1 in the cancer cells with a maximum increase occurring 8-24 h after heating. The sensitivity of cancer cells to beta-lap treatment progressively increased until 24 h after heating most likely due to the increase in NQO1 expression. Heating the FSaII tumors at 42 degrees C for 1 h and treating the host mice with an i.p. injection of 50 mg/kg beta-lap 24 h after the tumor heating was far more effective than heating alone or beta-lap treatment alone to suppress the tumor growth.
|
Mild temperature heat shock elevates the NQO1 expression in cancer cells, which in turn markedly increases the sensitivity of the cells to the bioreductive drug beta-lap in vitro and in vivo.
|
25,921,346 |
Do silent cerebral events as a result of left atrial catheter ablation cause neuropsychological sequelae -- a MRI-controlled multicenter study?
|
Recently, diffusion-weighted magnetic resonance imaging (DW-MRI) revealed silent cerebral events (SCEs) as an acute complication of pulmonary vein isolation (PVI). We investigated whether SCEs following PVI are associated with neuropsychological deficits observed during patients' follow-up examinations. After PVI, 52 patients were eligible for follow-up. PVI was performed using a variety of ablation technologies (duty-cycled phased radiofrequency (RF) multipolar ablation with the Pulmonary Vein Ablation Catheter® (PVAC) in 24 patients, cooled-tip RF ablation in 23 patients, and cryoballoon ablation in five patients). Fluid-attenuated inversion recovery (FLAIR)- and DW-MRI studies were performed 1 day before PVI and 1 day and 1 month afterward to detect pre-existing cerebral lesions or post-ablation SCEs. At the same times, eight neuropsychological tests were administered. We evaluated changes in patients' neuropsychological capabilities and compared changes in patients with SCEs to those without SCEs. FLAIR-MRI revealed pre-existing cerebral lesions in 42 patients (81 %), and DW-MRI demonstrated new SCEs in 25 patients (48 %) (17 treated with phased RF (PVAC) (71 %), six treated with irrigated RF (26 %), and two treated with cryoablation (40 %)). Neuropsychological test results showed no significant impairment (in median z scores) 1 day and 1 month after the ablation procedure. There was no difference in neuropsychological capabilities between patients with SCEs and those without SCEs except in one subtest (part of the verbal working memory test).
|
The incidence of pre-existing cerebral lesions and post-ablation SCEs was high. The frequency of SCEs depends on the ablation technology used. Neither PVI nor post-ablation SCEs have any effect on neuropsychological capabilities.
|
9,504,580 |
Are coronary constriction and consequent cardiodepression in pulmonary embolism mediated by pulmonary big endothelin and enhanced in early endothelial dysfunction?
|
Myocardial ischemia plays a central role in the development of right ventricular failure after acute pulmonary embolism. This study investigates whether pulmonary mediators act specifically on coronary tone and cardiac contractile function in acute pulmonary microembolization and whether such effects are altered in the case of early systemic atherosclerosis. We employ a novel model of serial perfusion in which an isolated rabbit heart is perfused with the effluent of the same animal's isolated lung. Controlled experiment using isolated organs. Experimental laboratory. Male New Zealand White rabbits (controls). Age-matched, male Watanabe rabbits (hypercholesterolemic, development of accelerated atherosclerosis). Seven isolated control and seven isolated Watanabe hearts were perfused with the saline effluent of the same animal's isolated lung. After the assessment of the baseline data, the lungs were gradually embolized with glass beads measuring 100 microm in diameter to induce an increase in mean pulmonary arterial pressure from 6 to 8 mm Hg, at baseline, up to 25 mm Hg. Pulmonary embolization to 25 mm Hg evoked a coronary constriction, measured as coronary flow decrease to 89 +/- 7% of the baseline value in controls. In the Watanabe group, coronary constriction was significantly enhanced, compared with controls, with coronary flow decreasing to 76 +/- 6% of the baseline value. In both groups, coronary constriction was followed by a deterioration in cardiac contractile performance. This cardiodepression was significantly deeper in Watanabe hearts with respect to both maximum ventricular pressures and maximum rates of pressure development and decline. Coronary constriction and cardiodepression were prevented by coronary infusion of the nonselective endothelin antagonist PD-145065, the endothelinA antagonists A-127722 and BQ-123, and the endothelin-converting enzyme inhibitor phosphoramidon. Concentration of big endothelin in pulmonary effluent increased from 5.6 +/- 0.3 pmol/L in controls and 5.6 +/- 0.2 pmol/L in the Watanabe group, at baseline, to 8.8 +/- 0.4 pmol/L in controls and 8.9 +/- 0.4 pmol/L in the Watanabe group, at 25 mm Hg pulmonary arterial pressure. Endothelin was not detectable at any time during the experiment in pulmonary effluent. The coronary gradient, calculated as a difference in concentration between coronary and pulmonary effluent, was negative for big endothelin and positive for endothelin in both groups.
|
We have demonstrated that an increase in pulmonary release of big endothelin occurs during lung embolism, which, in turn, results in coronary constriction and consequent cardiodepression. This action of big endothelin is based on its local coronary conversion into endothelin. In addition, coronary endothelial dysfunction, attributed to early systemic atherosclerosis, was shown to represent a specific risk factor in these events.
|
23,050,799 |
Does human α-defensin ( DEFA ) gene expression help to characterise benign and malignant salivary gland tumours?
|
Because of the infrequence of salivary gland tumours and their complex histopathological diagnosis it is still difficult to exactly predict their clinical course by means of recurrence, malignant progression and metastasis. In order to define new proliferation associated genes, purpose of this study was to investigate the expression of human α-defensins (DEFA) 1/3 and 4 in different tumour entities of the salivary glands with respect to malignancy. Tissue of salivary glands (n=10), pleomorphic adenomas (n=10), cystadenolymphomas (n=10), adenocarcinomas (n=10), adenoidcystic carcinomas (n=10), and mucoepidermoid carcinomas (n=10) was obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of DEFA 1/3 and 4 were analyzed by quantitative realtime PCR and compared with healthy salivary gland tissue. Additionally, the proteins encoded by DEFA 1/3 and DEFA 4 were visualized in paraffin-embedded tissue sections by immunohistochemical staining. Human α-defensins are traceable in healthy as well as in pathological altered salivary gland tissue. In comparison with healthy tissue, the gene expression of DEFA 1/3 and 4 was significantly (p<0.05) increased in all tumours - except for a significant decrease of DEFA 4 gene expression in pleomorphic adenomas and a similar transcript level for DEFA 1/3 compared to healthy salivary glands.
|
A decreased gene expression of DEFA 1/3 and 4 might protect pleomorphic adenomas from malignant transformation into adenocarcinomas. A similar expression pattern of DEFA-1/3 and -4 in cystadenolymphomas and inflamed salivary glands underlines a potential importance of immunological reactions during the formation of Warthin's tumour.
|
21,963,786 |
Do spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis?
|
The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP. CP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP. Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline.
|
Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.
|
21,911,911 |
Are [ Prevalence of respiratory symptoms and use of asthma drugs increasing among young adult Icelanders ]?
|
In the year 1990 the European Community Respiratory Health Survey I (ECRHS I) demonstrated that the prevalence of these diseases was lowest in Iceland (www.ecrhs.org). In order to compare the prevalence of respiratory symptoms in Reykjavik over time, a new identical cross-sectional study was performed seventeen years later. Both cohorts, were in the age group 20-44 years and randomly selected from the population in Reykjavik and suburbs. Both answered questionnaires about respiratory symptoms, nasal allergy and use of anti-asthmatic drugs. The second cohort was part of the EuroPrevall study (www.europrevall.org) performed in 2007. Response rate was lower in 2007 (999 or 43.2%) than in 1990 (2.903 or 80.6%).The prevalence of attacks of asthma increased over time from 2.2% to 6.7% (p<0.0001), use of anti-asthmatic drugs increased from 2.4% to 7.2% (p<0.0001) and nasal allergy symptoms from 17.8% to 29.3% (p< 0.0001). There was an increase of all respiratory symptoms except wheezing or whistling, where the prevalence dropped from 18.0% to 14.4% (p<0.01). In the year 2007 women had more often been woken by attacks of coughing (p<0.0001), had more often attacks of asthma (p<0.05) and were more likely to use anti-asthmatic drugs (p<0.05) than men. Attacks of asthma and the use of anti-asthmatic drugs were more common among the younger age group in the year 2007. That was not seen in the year 1990.
|
This study provides evidence of an increase in respiratory symptoms and use of anti-asthmatic drugs over a period of 17 years from 1990 among young adult Icelanders.
|
11,312,421 |
Do sentinel lymph node micrometastasis and other histologic factors that predict outcome in patients with thicker melanomas?
|
In patients with melanoma, lymph node staging information is obtainable by the surgical techniques of lymphatic mapping and sentinel lymph node (SLN) biopsy. Although no survival benefit has been proven for the procedure, the staging information is useful in identifying patients who may benefit from further surgery or adjuvant therapy. Currently, however, it is not being recommended for patients with thick melanomas (> 3-4 mm). The risk of hematogenous dissemination is considered too great in these patients. Recent studies indicate, however, that a surprising number of patients with thick melanomas become long-term survivors, and the lymph node status may be predictive. None of the conventional microscopic features used to gauge prognosis in patients with melanoma have proven helpful in distinguishing the survivors with thick melanoma from those who will die of their disease. Our purpose was to evaluate the influence of SLN histology and other microscopic parameters on survival of patients with thick melanomas. A computerized patient database at the Cutaneous Oncology Clinic at H. Lee Moffitt Cancer Center was accessed to obtain records on patients with melanomas thicker than 3.0 mm (AJCC T3b). A retrospective analysis was conducted with attention paid to histologic variables, sentinel node status, and survival. Survival curves were constructed with the Kaplan-Meier method, and a Cox-Mantel rank testing was used to establish statistical significance. Between 1991 and 1999, 201 patients were diagnosed with melanoma thicker than 3.0 mm, and 180 were alive at an average follow-up of 51 months. Of these, 166 were alive without disease. The mean overall and disease-free survival rates were 78% and 66%, respectively. There was a statistically significant difference in disease-free survival (3-year) between SLN-positive and SLN-negative patients (37% vs 73%, respectively; P =.02). The overall survival (3-year) for the SLN-positive patients was less than the node-negative patients (70% vs 82%), but it was not statistically significant (P =.08). The disease-free survival for patients with ulcerated lesions was less than for nonulcerated lesions (77% vs 93%, P =.05). None of the other histologic parameters studied, including Breslow thickness, Clark level, mitotic rate, or regression, had an influence on the overall or disease-free survival in this group of patients with thick tumors.
|
The results indicate that the SLN node status is predictive of disease-free survival for patients with thick melanomas. A surprising number of patients in the study were free of disease after prolonged follow-up. None of the histologic features of the primary tumor were helpful in predicting outcome, except for ulceration. SLN biopsy appears to be justified for prognostic purposes in patients with thick melanomas.
|
10,724,495 |
Do concentrations of leucocyte-associated chemotaxin C5a correlate with the mobilisation of polymorphonuclear leucocytes during operations for rectal cancer?
|
To describe the profile of potential chemotaxins C5a, interleukin 8 and tumour-necrosis factor alpha, and the peripheral blood leucocyte (PBL) response in five patients having uncomplicated operations for rectal cancer. Prospective study. University hospital, Norway. Five patients, four men and one woman, median age 66 years (range 48-77) who were operated on for rectal cancer. Four had low anterior resections and total mesorectal excision (TME) and one patient had a diverting end sigmoidostomy because of local perirectal spread of the cancer and liver metastases. Blood samples were taken at the start of the operation; peroperatively after 1, 2, and 3 hours; postoperatively at 5, 8, and 24 hours, for analysis of potential chemotaxins. The number of PBL tripled between the start and end of the operation and declined to a slightly lower plateau between 5 and 24 hours. Peroperatively, the association of C5a with PBL increased six-fold resulting in a doubled concentration of C5a/PBL, whereas the corresponding concentration of C5a in plasma remained relatively constant. Postoperatively, the concentration of C5a associated with the PBL and in plasma fluctuated with the maximums being at 8 and 24 hours, respectively. In contrast to C5a in plasma, the concentration of cell-associated C5a correlated with number of PBL or polymorphonuclear leucocytes (PMN). The plasma concentration of IL-8 doubled during the operation, reached a six-fold maximum at 5 hours, and declined after 24 hours to twice the initial concentration. There were no correlations between plasma IL-8 and either number of PBL, plasma C5a, or PBL-associated C5a. No TNF alpha was detected in the plasma.
|
Tissue trauma caused by uncomplicated excision of rectal cancer leads to leucocyte mobilisation peroperatively, probably partly by complement activation and subsequent generation and binding of the chemotaxin C5a to PBL. However, other chemotaxins may also play a role.
|
1,512,335 |
Is functional recovery after coronary revascularization for chronic coronary artery disease dependent on maintenance of oxidative metabolism?
|
This study was performed to define the importance of maintenance of oxidative metabolism as a descriptor and determinant of functional recovery after revascularization in patients with left ventricular dysfunction attributable to chronic coronary artery disease. Although myocardial accumulation of 18F-fluorodeoxyglucose indicates the presence of tissue that is metabolically active, it may not identify those metabolic processes required for restoration of myocardial contractility. Experimental studies suggest that, under conditions of ischemia and reperfusion, maintenance of myocardial oxidative metabolism is an important metabolic determinant of the capacity for functional recovery. In 16 patients positron emission tomography was performed to characterize myocardial perfusion (with H(2)15O), oxidative metabolism (with 11C-acetate) and utilization of glucose (with 18F-fluorodeoxyglucose). Dysfunctional but viable myocardium was differentiated from nonviable myocardium on the basis of assessments of regional function before and after coronary revascularization. To define the importance of coronary revascularization on myocardial perfusion and metabolism, tomography was repeated in 11 patients after revascularization. Before revascularization, perfusion in 24 dysfunctional but viable myocardial segments and 29 nonviable segments averaged 79% and 74%, respectively, of that in 42 normal myocardial segments (both p less than 0.01). Dysfunctional but viable myocardium exhibited oxidative metabolism comparable to that in normal myocardium. In contrast, in nonviable myocardium, oxidative metabolism was only 66% of that in normal (p less than 0.01) and 69% of that in reversibly dysfunctional myocardium (p less than 0.003). Regional utilization of glucose normalized to regional perfusion in dysfunctional but viable myocardium was greater than that in normal myocardium (p less than 0.01). However, in both reversibly and persistently dysfunctional myocardium, utilization of glucose normalized to relative perfusion was markedly variable.
|
The results indicate that preservation of oxidative metabolism is a necessary condition for recovery of function after coronary recanalization in patients with chronic coronary artery disease. Consequently, approaches that measure myocardial oxygen consumption, such as dynamic positron emission tomography with 11C-acetate, should facilitate the identification of those patients most likely to benefit from coronary revascularization.
|
11,929,651 |
Does induction of labor in twin pregnancy after 36 weeks increase maternal-fetal morbidity?
|
To compare maternal and perinatal outcomes in twin pregnancy patients without any fetal or maternal disease, managed by labor induction or expectant management after 36 weeks gestation. We conducted a case-control study of 81 patients: labor induction (n=36) vs. expectant management (n=45). Labor was induced using oxytocin (n=18), vaginal prostaglandins (n=6) or intrauterine balloon catheter (n=12) according to the Bishop score. Maternal and perinatal outcome variables were compared among both groups. The characteristics of the labor induction group and the expectant management group were not statistically different, except for the rate of nulliparae (55.6% vs. 33.3%) and the rate of epidural analgesia (100% vs. 80%). There was no significant difference in labor time (6.5+/-2.8 h vs. 6.0+/-3.6 h), cesarean section rate (8.3% vs. 13.3%) or duration of maternal hospitalization (7.3+/-2.0 days vs. 7.5+/-2.3 days) in the labor induction group and in the expectant management group, respectively. The birth weight was higher in the labor induction group than in the expectant management group (2639+/-352 g vs. 2463+/-298 g, P<0.001). The rate of Apgar score <7 at 5 min was 0% and 3.3%, respectively. Neonatal intensive care unit admission occurred in 30.5% and 26.6% of the groups, respectively. No perinatal death was reported.
|
Induction of labor may be proposed to patients with uneventful twin pregnancy after 36 weeks gestation without increasing maternal-fetal morbidity.
|
23,200,686 |
Does letrozole increase ovarian growth and Cyp17a1 gene expression in the rat ovary?
|
To evaluate the effects of letrozole on ovarian size and steroidogenesis in vivo, as well as on proliferation and steroidogenesis of theca-interstitial cells alone and in coculture with granulosa cells using an in vitro model. In vivo and in vitro studies. Research laboratory. Immature Sprague-Dawley female rats. In vivo effects of letrozole were studied in intact rats receiving either letrozole (90-day continuous-release SC pellets, 400 μg/d) or placebo pellets (control group). In in vitro experiments, theca cells were cultured alone or in coculture with granulosa cells in the absence or presence of letrozole. Deoxyribonucleic acid synthesis was determined by thymidine incorporation assay; steroidogenesis by mass spectrometry; and steroidogenic enzyme messenger RNA (mRNA) expression by polymerase chain reaction. In vivo, letrozole induced an increase in ovarian size compared with the control group and also induced a profound increase of androgen, LH levels, and Cyp17a1 mRNA expression. Conversely, a decrease in Star, Cyp11a1, and Hsd3b1 transcripts was observed in letrozole-exposed rats. In vitro, letrozole did not alter either theca cell proliferation or Cyp17a1 mRNA expression. Similarly, letrozole did not affect Cyp17a1 transcripts in granulosa-theca cocultures.
|
These findings suggest that letrozole exerts potent, but indirect, effect on growth of rat ovary and dramatically increases androgen levels and Cyp17a1 mRNA expression, the key enzyme regulating the androgen biosynthesis pathway. The present findings reveal novel mechanisms of action of letrozole in the rat ovary.
|
19,878,064 |
Do human bone marrow stem cells co-cultured with neonatal rat cardiomyocytes display limited cardiomyogenic plasticity?
|
This study investigated whether neonatal rat cardiomyocytes (NRCM), when co-cultured, can induce transdifferentiation of either human mesenchymal stromal cells (MSC) or hematopoietic stem cells (HSC) into cardiomyocytes. Stem cells were obtained from patients with ischemic heart disease. Ex vivo-expanded MSC or freshly isolated HSC were used to set-up a co-culture system between NRCM and MSC or HSC. 5-azacytidin (5-aza) or dimethylsulfoxide (DMSO) was used as differentiation-inducing factor. Co-cultured stem cells were separated from NRCM by flow sorting, and cardiac gene expression was analyzed by reverse transcriptase-polymerase chain reaction. Cellular morphology was analyzed by immunofluorescence and transmission electron microscopy (TEM). Co-culturing MSC induced expression of troponin T and GATA-4. However, no expression of alpha-actinin, myosin heavy chain or troponin I was detected. In the case of HSC, only expression of troponin T could be induced. Immunofluorescence and TEM confirmed the absence of sarcomeric organization in co-cultured MSC and HSC. Adding 5-aza or DMSO to the co-cultures did not influence differentiation.
|
This in vitro co-culture study obtained no convincing evidence of transdifferentiation of either MSC or HSC into functional cardiomyocytes. Nevertheless, induction of troponin T was observed in MSC and HSC, and GATA-4 in MSC. However, no morphologic changes could be detected by immunofluorescence or by TEM. These data could explain why only limited functional improvement was reported in clinical stem cell trials.
|
15,479,988 |
Is vitamin B6 level associated with symptoms of depression?
|
A low level of vitamin B6 might theoretically cause depression as vitamin B6 is a cofactor in the tryptophan-serotonin pathway. In the present study, we examined the association between depression and the phosphate derivative of vitamin B6 in plasma, pyridoxal phosphate (PLP). In 140 individuals, symptoms of depression were evaluated by the Major Depression Inventory, and biochemical markers of vitamin B deficiency were measured. We found that 18 (13%) individuals were depressed. A low plasma level of PLP was significantly associated with the depression score (p=0.002). No significant association was found between depression and plasma vitamin B12 (p=0.13), plasma methylmalonic acid (p=0.67), erythrocyte folate (p=0.77), and plasma total homocysteine (p=0.16).
|
Our study suggests that a low level of plasma PLP is associated with symptoms of depression. Randomized trials are now justified and needed in order to examine whether treatment with vitamin B6 may improve symptoms of depression.
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.