bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Results of Concurrent Arthroscopic Repair of Rotator Cuff and Type II Superior Labral Anterior Posterior Tears
Authors: Strickland Justin P. , Fleckenstein Cassie M. , Ducker Al , Hasan Samer S.
Published: July 2010

Background:

Recent reports on concurrent arthroscopic rotator cuff and type II superior labral anterior posterior (SLAP) repair have raised concerns over postoperative stiffness and patient satisfaction. However, it is unclear if the observed stiffness relates to the repair of degenerative SLAP tears in older adults, the surgical technique, the postoperative rehabilitation, or to a combination of these factors.

Purpose:

The purpose of this study was to evaluate the outcome and repair integrity of concurrent arthroscopic rotator cuff and type II SLAP repair.

Study Design:

Case series.

Methods:

Of 11 patients identified, 7 had a full-thickness rotator cuff tear and 4 had a high-grade partial thickness tear that was completed. A cannula placed through the rotator cuff tear improved the trajectory for posterior suture anchor placement during SLAP repair. Postoperative rehabilitation employed continuous passive motion to prevent stiffness.

Results:

At minimum of 1-year follow-up, mean yes responses on the Simple Shoulder Test improved from 5.4 to 10.7 (out of 12; P < .01), and mean American Shoulder and Elbow Surgeons scores improved from 40 to 87 (out of 100; P < .01). Mean forward elevation improved from 148° to 161° ( P < .01) and external rotation from 58° to 67° ( P < .01). Magnetic resonance imaging, obtained at most recent follow-up in 10 patients, demonstrated a healed SLAP tear in all patients and a persistent rotator cuff defect in 1 patient.

Conclusions:

Arthroscopic rotator cuff repair can be successfully combined with type II SLAP repair in relatively young patients who have sustained traumatic injury to their shoulders. Allowing early passive motion may help prevent postoperative stiffness without compromising rotator cuff healing.
Oxide ionic conductivity and crystallographic properties of tetragonal type Bi2O3-based solid electrolyte doped with Ho2O3
Authors: Bozoklu M. , Turkoglu O. , Yılmaz S. , Arı M. , Belenli I.
Published: July 2010

In the present work, the authors have investigated the binary system of (Bi2O3)1–x(Ho2O3)x. For the stabilisation of the tetragonal type solid solution, small amounts of Ho2O3 were doped into the monoclinic Bi2O3 via solid state reactions in the stoichiometric range 0·01≤x≤0·1. The crystal formula of the formed solid solution was determined as Bi(III)4–4xHo(II)4xO6–2xVo(2+2x) (where Vo is the oxide ion vacancy) according to the XRD and SEM microprobe results. In the crystal formula, stoichiometric values of x were 0·04≤x≤0·08, 0·03≤x≤0·09, 0·02≤x≤0·09 and 0·04≤x≤0·09 for annealing temperatures at 750, 800, 805 (quench) and 760°C (quench) respectively. The four probe electrical conductivity measurements showed that the studied system had an oxide ionic type electrical conductivity behaviour, which is increased with increasing dopant concentration and temperature. The obtained solid electrolyte system has an oxygen non-stoichiometry characteristic, and it contains O2– vacancies, which have disordered arrangements in its tetragonal crystal structure. The increase in the amount of Ho2O3 doping and temperature causes an increasing degree of the disordering of oxygen vacancies and a decrease in the activation energy Ea.
ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion
Authors: Bles Nathalie , Di Pietrantonio Larissa , Boeynaems Jean-Marie , Communi Didier
Published: July 2010

ATP, which has an important proinflam-matory action as danger signal, induces the semimaturation of dendritic cells (DCs) that can be associated with immune tolerance. We identified epidermal growth factor receptor ligands as target genes of ATPγS, a slowly hydrolyzed ATP derivative, by a gene profiling approach in DCs. Amphiregulin was the most highly up-regulated gene in response to ATPγS. Human monocyte–derived DCs and mouse bone marrow–derived DCs released amphiregulin (AREG) after purinergic receptor activation, with a contribution of P2Y11 and A2B receptor, respectively. Supernatants of LPS+ATPγS-stimulated DCs induced smooth muscle cell and Lewis Lung Carcinoma (LLC) cell growth in vitro. The coinjection of LPS+ATPγS-stimulated DCs or their supernatants with LLC cells increased tumor weight in mice compared with LPS-treated DCs. The preincubation of LPS+ATPγS-treated DC supernatants with an anti-AREG blocking antibody inhibited their positive effect on smooth muscle cell density and tumor growth. The present study demonstrates for the first time that DCs can be a source of AREG. ATP released from tumor cells might exert a tumorigenic action by stimulating the secretion of AREG from DCs. Antagonists of purinergic receptors expressed on DCs and anti-AREG blocking antibodies could have a therapeutic potential as antitumor agents.
Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903
Authors: Mesa Ruben A. , Yao Xiaopan , Cripe Larry D. , Li Chin Yang , Litzow Mark , Paietta Elisabeth , Rowe Jacob M. , Tefferi Ayalew , Tallman Martin S.
Published: July 2010

A multicenter Eastern Cooperative Group (ECOG) phase 2 trial assessed whether adding prednisone to lenalidomide would improve previously reported responses in persons with myelofibrosis (MF). Forty-eight subjects with anemia (42 evaluable) received lenalidomide, 10 mg/d, with a 3-month low-dose prednisone taper. Ten subjects received 3 months, and 25 received 6 months of therapy. Myelosuppression was the main toxicity with 88% with ≥ grade 3 hematologic toxicity and 45% ≥ grade 3 nonhematologic toxicity. There were responses in 10 subjects (23%) using the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)–defined clinical improvement of anemia in 8 (19%) and/or decreased spleen size in 4 (10%). Serial bone marrow analysis showed no resolution of disease-related fibrosis or angiogenesis. With a median follow-up of 2.3 years, 23 subjects are alive. Lenali-domide and prednisone for myelofibro-sis evaluated through a multicentered-cooperative group mechanism is only modestly active and myelosuppre-sive. This study was registered at http://clinicaltrials.gov as NCT00227591.
Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2
Authors: Mitola Stefania , Ravelli Cosetta , Moroni Emanuela , Salvi Valentina , Leali Daria , Ballmer-Hofer Kurt , Zammataro Luca , Presta Marco
Published: July 2010

The bone morphogenic protein antagonist gremlin is expressed during embryonic development and under different pathologic conditions, including cancer. Gremlin is a proangiogenic protein belonging to the cystine-knot superfamily that includes transforming growth factor-β proteins and the angiogenic vascular endothelial growth factors (VEGFs). Here, we demonstrate that gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals, in a bone morphogenic protein–independent manner. Similar to VEGF-A, gremlin activates VEGFR2 in endothelial cells, leading to VEGFR2-dependent angiogenic responses in vitro and in vivo. Gremlin thus represents a novel proangiogenic VEGFR2 agonist distinct from the VEGF family ligands with implications in vascular development, angiogenesis-dependent diseases, and tumor neovascularization.
Validity of spirometry performed online
Authors: Masa J.F. , González M.T. , Pereira R. , Mota M. , Riesco J.A. , Corral J. , Zamorano J. , Rubio M. , Teran J. , Farré R.
Published: July 2010

Spirometry is essential for the diagnosis and management of common respiratory diseases. However, its use and quality are low in primary care. An important reason for this is the technical difficulty in performing conventional spirometry. If high-quality spirometry could be performed online, from the pulmonary function laboratory in hospitals, most of the technical problems could be solved. The aim of the present study was to compare spirometries performed online by remote technicians with conventional spirometry.

This was a controlled, randomised crossover study of 261 patients referred from primary care centres for pulmonary consultation. They were randomised to undergo either conventional or online spirometry. The technician, located remotely, controlled the spirometer computer. Using a teleconference link, the technician guided the patient through the spirometry. The comparison between conventional and online spirometries was performed on intention to treat and per protocol bases for spirometric values and quality criteria. Agreement between the two spirometric methods was assessed with a Bland–Altman plot. A subpopulation of off-range patients was also characterised. Finally, intra- and interobserver agreement was evaluated using the intraclass correlation coefficient.

No clinically significant differences were seen between the online and conventional spirometric values in both the intention to treat and per protocol analyses. The agreement in Bland–Altman analysis was poorer for intention to treat than for the per protocol analysis. The latter had a lower percentage of off-range patients and high agreement to determine abnormal spirometry in the off-range group. Conventional spirometry had a higher percentage of patients with spirometric quality criteria although the quality criteria difference was only 5.9%, when both procedures were the first to start. Very good agreement was found between intra- and interobserver reliability.

Spirometry performed online from a hospital can be an adequate alternative to conventional spirometry for primary care centres.
Relationship of oxidative stress and endothelial dysfunction in sleep apnoea
Authors: Jurado-Gámez B. , Fernandez-Marin M.C. , Gómez-Chaparro J.L. , Muñoz-Cabrera L. , Lopez-Barea J. , Perez-Jimenez F. , Lopez-Miranda J.
Published: July 2010

The aim of the present study was to evaluate ischaemic reactive hyperaemia (IRH) in obstructive sleep apnoea (OSA) and its relationship with oxidative stress.

We studied 69 consecutive patients referred to our Sleep Unit (Reina Sofia University Hospital, Cordoba, Spain). Patients with chronic diseases or those taking medication were excluded. IRH was assessed before and after polysomnography. Morning IRH and oxidative stress markers were compared between patients with (apnoea–hypopnoea index (AHI) ≥5) and without (AHI <5) OSA. Measurements were repeated in 25 severe OSA patients after continuous positive airway pressure (CPAP) therapy.

We included 46 OSA patients (mean±sdAHI 49±32.1) and 23 non-OSA subjects (AHI 3±0.9). The OSA patients showed a significant worsening of morning IRH, and a significant increase in malondialdehyde and 8-hydroxydeoxyguanosine levels. Only the oxygen desaturation index independently explained morning IRH, while malondialdehyde levels showed a weak effect on IRH. In severe OSA patients, IRH improved significantly after CPAP treatment, as did malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyl levels.

In OSA patients, endothelial dysfunction and oxidative stress were observed, and IRH worsened after sleep. The increase in oxidative stress was not associated with IRH, while intermittent hypoxia was strongly associated with IRH. In severe OSA patients, CPAP treatment improved oxidative stress and endothelial function.
Cisplatin nephrotoxicity aggravated by cardiovascular disease and diabetes in lung cancer patients
Authors: Máthé C. , Bohács A. , Duffek L. , Lukácsovits J. , Komlosi Z.I. , Szondy K. , Horváth I. , Müller V. , Losonczy G.
Published: July 2010

Ageing lung cancer patients may be at increased risk of Cisplatin (Cp) nephrotoxicity, because of comorbidities leading to accelerated ageing of the kidneys. Therefore, the Cp-induced impairement of renal function was compared between no comorbidity (NC) and hypertension plus ischaemic heart disease (CD) patients or others having diabetes mellitus plus ischaemic heart disease (DMIH).

In a preliminary study, glomerular filtration rate (GFR) was measured by clearance of technetium 99m-labelled diethylene-thiamine penta-acetate in 38 lung cancer patients with normal serum creatinine concentration ([creat]). Then, the incidence of nephrotoxicity was analysed retrospectively over 1st–4th cycles of Cp treatment among 242 lung cancer patients with initially normal [creat]. GFR was repeatedly estimated using calculated creatinine clearance.

Pre-treatment GFR was 57±3 mL·min−1·m−2in those with normal (n = 15) and 42±2 mL·min−1·m−2in those with pathologically increased (n = 23) [creat] any time following their 2nd–4th Cp cycle (p<0.05). The retrospective analysis revealed that Cp-induced nephrotoxicity developed in 7.5% of the NC (n = 80), in 20.9% of the CD (n = 110) and in 30.8% of the DMIH (n = 52) subgroups. Within the overall dropout rate from further Cp chemotherapy, nephrotoxicity was responsible in 14% of NC, 38% in CD and 75% in DMIH patients.

A major portion of our ageing lung cancer patients suffered from comorbidities leading to reduced renal resistance to Cp nephrotoxicity.
Impaired function of regulatory T-cells in hypersensitivity pneumonitis
Authors: Girard M. , Israël-Assayag E. , Cormier Y.
Published: July 2010

Hypersensitivity pneumonitis (HP) is characterised by lung lymphocytosis. Most individuals exposed to HP antigens remain asymptomatic. The mechanisms involved in the impaired immune tolerance leading to HP are unclear. Normally, T-regulatory (Treg)-cells control the immune response. The aim of the present study was to determine whether Treg-cell suppressive function deficiency can explain the uncontrolled inflammation in HP.

Bronchoalveolar lavage (BAL) and blood samples were obtained from normal subjects, asymptomatic individuals and HP patients. BAL and blood Treg-cells were isolated. The ability of Treg-cells to suppress T-cell proliferation and the role of interleukin (IL)-17 was verified.

BAL and blood Treg-cells from normal subjects suppressed the proliferative response of activated T-cells by 47.1 and 42%, respectively. BAL and blood Treg-cells from asymptomatic subjects had a slightly decreased activity and suppressed proliferation by 29.4 and 31.8%, respectively. BAL and blood Treg-cells from HP patients were totally nonfunctional and unable to suppress proliferation. Low levels of IL-17 were detected in sera and BAL from both normal and asymptomatic individuals, whereas measurable levels were found in patients.

Treg-cells may be involved in antigen tolerance in asymptomatic subjects. Defective Treg-cell function, potentially caused by increased IL-17 production, could account for the exacerbated immune response characteristic of HP.
The shock index and the simplified PESI for identification of low-risk patients with acute pulmonary embolism
Authors: Sam A. , Sánchez D. , Gómez V. , Wagner C. , Kopecna D. , Zamarro C. , Moores L. , Aujesky D. , Yusen R. , Jiménez Castro D.
Published: July 2010

We compared the test characteristics of the shock index (SI) and the simplified pulmonary embolism severity index (sPESI) for predicting 30-day outcomes in a cohort of 1,206 patients with objectively confirmed pulmonary embolism (PE).

The primary outcome of the study was all-cause mortality. The secondary outcome was nonfatal symptomatic recurrent venous thromboembolism (VTE) or nonfatal major bleeding.

Overall, 119 (9.9%) out of 1,206 patients died (95% CI 8.2–11.5%) during the first month of follow-up. The sPESI classified fewer patients as low-risk (369 (31%) out of 1,206 patients, 95% CI 28–33%) compared to the SI (1,024 (85%) out of 1,206 patients, 95% CI 83–87%) (p<0.001). Low-risk patients based on the sPESI had a lower 30-day mortality than those based on the SI (1.6% (95% CI 0.3–2.9%)versus8.3% (95% CI 6.6–10.0%)), while the 30-day rate of nonfatal recurrent VTE or major bleeding was similar (2.2% (95%CI 0.7–3.6%)versus3.3% (95%CI 2.2–4.4%)). The net reclassification improvement with the sPESI was 13.4% (p = 0.07). The integrated discrimination improvement was estimated as 1.8% (p<0.001).

The sPESI quantified the prognosis of patients with PE better than the SI.
An insight into the sialotranscriptome of the brown dog tick, Rhipicephalus sanguineus
Authors: Anatriello Elen , Ribeiro José MC , de Miranda-Santos Isabel KF , Brandão Lucinda G , Anderson Jennifer M , Valenzuela Jesus G , Maruyama Sandra R , Silva João S , Ferreira Beatriz R
Published: July 2010

Background

Rhipicephalus sanguineus, known as the brown dog tick, is a common ectoparasite of domestic dogs and can be found worldwide. R.
sanguineus is recognized as the primary vector of the etiological agent of canine monocytic ehrlichiosis and canine babesiosis. Here we present the first description of a R. sanguineus salivary gland transcriptome by the production and analysis of 2,034 expressed sequence tags (EST) from two cDNA libraries, one consctructed using mRNA from dissected salivary glands from female ticks fed for 3-5 days (early to mid library, RsSGL1) and the another from ticks fed for 5 days (mid library, RsSGL2), identifying 1,024 clusters of related sequences.

Results

Based on sequence similarities to nine different databases, we identified transcripts of genes that were further categorized according to function. The category of putative housekeeping genes contained ~56% of the sequences and had on average 2.49 ESTs per cluster, the secreted protein category contained 26.6% of the ESTs and had 2.47 EST's/clusters, while 15.3% of the ESTs, mostly singletons, were not classifiable, and were annotated as "unknown function". The secreted category included genes that coded for lipocalins, proteases inhibitors, disintegrins, metalloproteases, immunomodulatory and antiinflammatory proteins, as Evasins and Da-p36, as well as basic-tail and 18.3 kDa proteins, cement proteins, mucins, defensins and antimicrobial peptides. Comparison of the abundance of ESTs from similar contigs of the two salivary gland cDNA libraries allowed the identification of differentially expressed genes, such as genes coding for Evasins and a thrombin inhibitor, which were over expressed in the RsSGL1 (early to mid library) versus RsSGL2 (mid library), indicating their role in inhibition of inflammation at the tick feeding site from the very beginning of the blood meal. Conversely, sequences related to cement (64P), which function has been correlated with tick attachment, was largely expressed in the mid library.

Conclusions

Our survey provided an insight into the R. sanguineus sialotranscriptome, which can assist the discovery of new targets for anti-tick vaccines, as well as help to identify pharmacologically active proteins.
Rapid induction of orthotopic hepatocellular carcinoma in immune-competent rats by non-invasive ultrasound-guided cells implantation
Authors: Chan Hoi-Hung , Chu Tian-Huei , Chien Hsin-Fan , Sun Cheuk-Kwan , Wang E-Ming , Pan Huay-Ben , Kuo Hsiao-Mei , Hu Tsung-Hui , Lai Kwok-Hung , Cheng Jiin-Tsuey , Tai Ming-Hong
Published: July 2010

Background

The fact that prognoses remain poor in patients with advanced hepatocellular carcinoma highlights the demand for suitable animal models to facilitate the development of anti-cancer medications. This study employed a relatively non-invasive approach to establish an orthotopic hepatocellular carcinoma model in immune-competent rats. This was done by ultrasound-guided implantation of cancer cells and the model was used to evaluate the therapeutic efficacy of short-term and low-dose epirubicin chemotherapy.

Methods

Rat Novikoff hepatoma cells were injected percutaneously into the liver lobes of Sprague-Dawley rats under the guidance of high resolution ultrasound. The implantation rate and the correlation between dissected and ultrasound-measured tumor sizes were evaluated. A similar induction procedure was performed by means of laparotomy in a different group of rats. Pairs of tumor measurement were compared by ultrasound and computerized tomography scan. Rats with a successful establishment of the tumor were divided into the treatment (7-day low-dose epirubicin) group and the control group. The tumor sizes were non-invasively monitored by the same ultrasound machine. Blood and tumor tissues from tumor-bearing rats were examined by biochemical and histological analysis respectively.

Results

Ultrasound-guided implantation of Novikoff hepatoma cells led to the formation of orthotopic hepatocellular carcinoma in 60.4% (55/91) of the Sprague-Dawley rats. Moreover, tumor sizes measured by ultrasound significantly correlated with those measured by calipers after sacrificing the animals (P < 0.00001). The rate of tumor induction by ultrasound-guided implantation was comparable to that of laparotomy (55/91, 60.4% vs. 39/52, 75%) and no significant difference in sizes of tumor was noted between the two groups. There was a significant correlation in tumor size measurement by ultrasound and computerized tomography scan. In tumor-bearing rats, short-term and low-dose epirubicin chemotherapy caused a significant reduction in tumor growth, and was found to be associated with enhanced apoptosis and attenuated proliferation as well as a decrease in the microvessel density in tumors.

Conclusions

Ultrasound-guided implantation of Novikoff hepatoma cells is an effective means of establishing orthotopic hepatocellular carcinoma in Sprague-Dawley rats. Short-term and low-dose epirubicin chemotherapy had perturbed tumor progression by inducing apoptosis and neovascularization blockade.
Mutational spectrum of APC and genotype-phenotype correlations in Greek FAP patients
Authors: Fostira Florentia , Thodi Georgia , Sandaltzopoulos Raphael , Fountzilas George , Yannoukakos Drakoulis
Published: July 2010

Background

Familial adenomatous polyposis, an autosomal dominant inherited disease caused by germline mutations within the APC gene, is characterized by early onset colorectal cancer as a consequence of the intrinsic phenotypic feature of multiple colorectal adenomatic polyps. The genetic investigation of Greek adenomatous polyposis families was performed in respects to APC and MUTYH germline mutations. Additionally, all available published mutations were considered in order to define the APC mutation spectrum in Greece.

Methods

A cohort of 25 unrelated adenomatous polyposis families of Greek origin has been selected. Genetic testing included direct sequencing of APC and MUTYH genes. APC gene was also checked for large genomic rearrangements by MLPA.

Results

Analysis of the APC gene performed in a Greek cohort of twenty five FAP families revealed eighteen different germline mutations in twenty families (80%), four of which novel. Mutations were scattered between exon 3 and codon 1503 of exon 15, while no large genomic rearrangements were identified.

Conclusion

This concise report describes the spectrum of all APC mutations identified in Greek FAP families, including four novel mutations. It is concluded that the Greek population is characterized by genetic heterogeneity, low incidence of genomic rearrangements in APC gene and lack of founder mutation in FAP syndrome.
Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study
Authors: Russell Elizabeth C , Charalambous Salome , Pemba Lindiwe , Churchyard Gavin J , Grant Alison D , Fielding Katherine
Published: July 2010

Background

Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people with HIV infection; however, mortality after the start of ART is high in resource-limited settings. We investigated risk factors for mortality among adults starting ART in a multi-clinic community programme in South Africa.

Methods

Cohort of adults starting ART at 27 clinics between February 2005 and June 2006, followed to 31stMarch 2007. Kaplan-Meier survival estimates were used to describe overall mortality. Shared frailty Cox regression was used to identify baseline risk factors for early mortality.

Results

Among 1350 participants (median age 35.5 years, 60% female, median CD4 count 83/μL [interquartile range (27 - 147)], median follow-up 13.4 months), there were 185 deaths, overall mortality rate 13/100 pyrs; for 0-3, 3-9 and >9 months from ART start mortality rates were 24, 13 and 6/100 pyrs respectively. 43% of the deaths were in the first 3 months of treatment. Risk factors for mortality in univariable analysis were baseline CD4 count, viral load, haemoglobin and body mass index, in multivariable analysis adjusting for age and gender, only CD4 count and haemoglobin remained independently associated with proportional hazards not being satisfied for haemoglobin. Adjusted hazard ratios (aHR) for participants with haemoglobin <8, 8.1-9.9, >11.9(f)/12.9 (m) g/mL were 4.99, 3.05 and 0.12 respectively comparing to 10-11.9 (f)/12.9 (m)g/mL in the first 3 months of ART. aHRs for CD4 counts were 0.40, 0.38 and 0.34 for 50-99, 100-200 and >200/μL comparing to <50/μL.

Conclusions

The high mortality rate in the first 3 months underlines the need for earlier HIV diagnosis so that ART can be initiated earlier. Low haemoglobin and low CD4 count are both strong predictors of mortality, and could be used to identify individuals at high risk who might benefit from intensive case management.
Anthropometric, biochemical and clinical assessment of malnutrition in Malaysian patients with advanced cirrhosis
Authors: Tai Mei-Ling S , Goh Khean-Lee , Mohd-Taib Siti Hawa , Rampal Sanjay , Mahadeva Sanjiv
Published: July 2010

Background

There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies.

Methodology

A cross-sectional study of adult patients with decompensated cirrhosis was conducted. Nutritional status was assessed using standard anthropometry, serum visceral proteins and subjective global assessment (SGA).

Results

Thirty six patients (mean age 59.8 ± 12.8 years; 66.7% males; 41.6% viral hepatitis; Child-Pugh C 55.6%) with decompensated cirrhosis were recruited. Malnutrition was prevalent in 18 (50%) patients and the mean caloric intake was low at 15.2 kcal/kg/day. SGA grade C, as compared to SGA grade B, demonstrated significantly lower anthropometric values in males (BMI 18.1 ± 1.6 vs 26.3 ± 3.5 kg/m2, p < 0.0001; MAMC 19.4 ± 1.5 vs 24.5 ± 3.6 cm, p = 0.002) and females (BMI 19.4 ± 2.7 vs 28.9 ± 4.3, p = 0.001; MAMC 18.0 ± 0.9 vs 28.1 ± 3.6, p < 0.0001), but not with visceral proteins. The SGA demonstrated a trend towards more malnutrition in Child-Pugh C compared to Child-Pugh B liver cirrhosis (40% grade C vs 25% grade C, p = 0.48). Alcoholic cirrhosis had a higher proportion of SGA grade C (41.7%) compared to viral (26.7%) and cryptogenic (28.6%) cirrhosis, but this was not statistically significant.

Conclusion

Significant malnutrition in Malaysian patients with advanced cirrhosis is common. Alcoholic cirrhosis may have more malnutrition compared to other aetiologies of cirrhosis.
CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion
Authors: Johnson Erica L , Singh Rajesh , Singh Shailesh , Johnson-Holiday Crystal M , Grizzle William E , Partridge Edward E , Lillard James W
Published: July 2010

Background

Ovarian carcinoma (OvCa) is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells and its only natural ligand, CCL25, is largely expressed in the thymus, which involutes with age. Other than the thymus, CCL25 is expressed by the small bowel. Interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for OvCa cells. The current study shows OvCa tissue and cells significantly express CCR9, which interacts with CCL25 to support carcinoma cell migration and invasion.

Methods

RT-PCR and flow cytometry techniques were used to quantify the expression CCR9 by OvCa cells. OvCa tissue microarrays (TMA) was used to confirm CCR9 expression in clinical samples. The Aperio ScanScope scanning system was used to quantify immunohistochemical staining. Cell invasion and migration assays were performed using cell migration and matrigel invasion chambers. Matrix metalloproteinase (MMP) mRNAs were quantified by RT-PCR and active MMPs were quantified by ELISA.

Results

Our results show significantly (p< 0.001) higher expression of CCR9 by mucinous adenocarcinoma, papillary serous carcinoma, and endometriod ovarian carcinoma cases, than compared to non-neoplastic ovarian tissue. Furthermore, CCR9 expression was significantly elevated in OvCa cell lines (OVCAR-3 and CAOV-3) in comparison to normal adult ovarian epithelial cell mRNA. OvCa cells showed higher migratory and invasive potential towards chemotactic gradients of CCL25, which was inhibited by anti-CCR9 antibodies. Expression of collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), and stromelysins (MMP-3, -10, and -11) by OvCa cells were modulated by CCL25 in a CCR9-dependent fashion.

Conclusions

These results demonstrate both biological significance and clinical relevance of CCL25 and CCR9 interactions in OvCa cell metastasis.
The impact of non-significant variable decelerations appearing in the latent phase on delivery mode: a prospective cohort study
Authors: Salim Raed , Garmi Gali , Nachum Zohar , Shalev Eliezer
Published: July 2010

Background

Variable decelerations are the most frequent fetal heart rate changes that are related to labor. The objective of the study was to estimate the impact of non-significant variable decelerations (NSV) appearing during the latent phase of labor on delivery mode and neonatal outcome.

Methods

Women at term, who were in the latent phase of labor and had a singleton pregnancy, were prospectively included. Women were divided into three groups. All had a fetal heart rate tracing with normal baseline and variability. The study group was composed of women who had in addition NSV, Category II, according to the National Institute of Child Health and Human Development categorization system. Women who had Category I tracings composed the control group. Women who had non-repetitive severe variables (SV) composed a second control group (Category II-SV). Main outcome compared was mode of delivery. Secondary outcome was cord pH. One-way analysis of variance was used to compare the continuous demographic and clinical variables of the three groups. Backwards stepwise logistic regression using significant univariables was performed to determine which predicted operative delivery. P < 0.05 was considered significant.

Results

Of 1005 women who delivered during the study period 186 had Category II- NSV tracings (study group), 76 had Category II-SV and 251 had Category I tracings. Mode of delivery and indications for operative delivery were similar between women in Category II-NSV compared to Category I. In addition mean cord pH did not differ between the two groups. Conversely, women in Category II-SV, had a higher rate of cesarean or vacuum deliveries compared to the other groups (p = 0.0001). Beside, they had a significantly higher number of neonates born with cord pH between 7.0 to 7.1 (p = 0.03).

Conclusions

Non-significant variable decelerations in early stages of labor are probably a non-ominous sign for neonatal outcome and have no impact on delivery mode.
Heterologous SH3-p85β inhibits influenza A virus replication
Authors: Zhang Dan-gui , Li Wei-zhong , Wang Ge-fei , Su Yun , Zeng Jun , Zhang Chi , Zeng Xiang-xing , Chen Xiao-xuan , Xu Yan-xuan , Li Kang-sheng
Published: July 2010

Phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway can support the replication of influenza A virus through binding of viral NS1 protein to the Src homology 3 (SH3) domain of p85β regulatory subunit of PI3K. Here we investigated the effect of heterologously overexpressed SH3 on the replication of different influenza A virus subtypes/strains, and on the phosphorylation of Akt in the virus-infected cells. We found that heterologous SH3 reduced replication of influenza A viruses at varying degrees in a subtype/strain-dependent manner and SH3 overexpression reduced the induction of the phosphorylation of Akt in the cells infected with PR8(H1N1) and ST364(H3N2), but not with ST1233(H1N1), Ph2246(H9N2), and Qa199(H9N2). Our results suggest that interference with the NS1-p85β interaction by heterologous SH3 can be served as a useful antiviral strategy against influenza A virus infection.
Predictive relevance of HOXB13 protein expression for tamoxifen benefit in breast cancer
Authors: Jerevall Piiha-Lotta , Jansson Agneta , Fornander Tommy , Skoog Lambert , Nordenskjöld Bo , Stål Olle
Published: July 2010

Introduction

The HOXB13:IL17BR index has been identified to predict clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer. Further studies have shown that HOXB13 in particular can indicate benefit of prolonged tamoxifen treatment. Patients with high-expressing tumors did not benefit from prolonged treatment, suggesting that HOXB13 might be involved in tamoxifen resistance. No studies have been made regarding the HOXB13 protein levels in breast cancer. The aim of our study was to investigate whether tamoxifen benefit can be correlated to different levels of HOXB13 protein expression.

Methods

We used immunohistochemistry to analyze protein levels of HOXB13 in tumor samples from 912 postmenopausal node-negative breast cancer patients randomized to adjuvant tamoxifen therapy or no endocrine treatment.

Results

Tamoxifen-treated patients with estrogen receptor-positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (DRFS) (hazard ratio = 0.38, 95% confidence interval = 0.23 to 0.60, P = 0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the DRFS compared with the untreated patients (hazard ratio = 0.88, 95% confidence interval = 0.47 to 1.65, P = 0.69). Interaction between HOXB13 expression and benefit from tamoxifen was statistically significant for DRFS (P = 0.035). No prognostic value could be ascribed to HOXB13 among systemically untreated patients.

Conclusions

A high HOXB13 expression was associated with decreased benefit from tamoxifen, which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment.
Standardized intensive care unit management in an anhepatic pig model: new standards for analyzing liver support systems
Authors: Thiel Christian , Thiel Karolin , Etspueler Alexander , Schenk Thomas , Morgalla Matthias H , Koenigsrainer Alfred , Schenk Martin
Published: July 2010

Introduction

Several anhepatic pig models were developed in the past. Most models suffer from short anhepatic survival times due to insufficient postoperative intensive care unit (ICU) management. The aim of this study was to analyze anhepatic survival time under standardized intensive care therapy in a pig model.

Methods

Eight pigs underwent total hepatectomy after Y-graft interposition between the infrahepatic vena cava and the portal vein to the suprahepatic vena cava. An intracranial probe was inserted for intracranial pressure (ICP) monitoring. Animals received pressure-controlled ventilation under deep narcosis. Vital parameters were continuously recorded. Urinary output, blood gas analysis, haemoglobin, hematocrit, serum electrolytes, lactate, and glucose were monitored hourly, and creatinine, prothrombin time, international normalised ratio, and serum albumin were monitored every 8 hours. Sodium chloride solution 0.9%, hydroxyethyl starch 6%, fresh frozen plasma, and erythrocyte units were used for volume substitution, and norepinephrine was used to prevent severe hypotension. Serum electrolytes and acid-base balance were corrected as required. Antibiotic prophylaxis with ceftriaxon was given daily, as well as furosemide, to maintain diuresis.

Results

Postoperative survival was 100% after 24 hours, with a maximum survival of 73 (mean, 58 ± 4) hours. Haemodynamic parameters such as heart rate, mean arterial pressure, and pulse oximetry remained stable during surgical procedures and following anhepatic status due to ICU therapy until escalating at time of death. Deteriorating pulmonary function could be stabilized by increasing oxygen concentration, positive end-expiratory pressure, and maximal airway pressure. Furosemide was used to maintain diuresis until renal failure occurred. ICP started at 15-17 mmHg and increased continuously up to levels of 41-43 mmHg at time of death. All animals died as a result of multiple-organ failure.

Conclusions

Using standardized intensive care management after total hepatectomy, we were able to prolong anhepatic survival over 58 hours without the use of liver support systems. The survival benefit of liver support systems in previous animal studies should be reevaluated against our model.
Ligand-Independent Antiapoptotic Function of Estrogen Receptor-β in Lung Cancer Cells
Authors: Zhang GuangFeng , Yanamala Naveena , Lathrop Kira L. , Zhang Lin , Klein-Seetharaman Judith , Srinivas Harish
Published: July 2010

Recent studies have demonstrated the presence of estrogen receptor (ER)β in the mitochondria in various cell types and tissues, but the exact function of this localization remains unclear. In this study, we have examined the function of mitochondrial ERβ in non-small-cell lung cancer (NSCLC) cells. Down-regulation of ERβ by short hairpin RNA constructs sensitized NSCLC cells to various apoptosis-inducing agents such as cisplatin, taxol, and etoposide. The increased growth inhibition and induction of apoptosis in ERβ-knockdown cells was observed irrespective of estrogen treatment, suggesting a ligand-independent role of ERβ in regulating the intrinsic apoptotic pathway. Further, ERβ from the mitochondrial fraction physically interacted with the proapoptotic protein Bad, in a ligand-independent manner. Glutathione-S-transferase pull-down assays and molecular modeling studies revealed that the DNA-binding domain and hinge region of ERβ, and the BH3 domain of Bad were involved in these interactions. Further investigations revealed that ERβ inhibited Bad function by disrupting Bad-Bcl-XL and Bad-Bcl-2 interactions. Reintroduction of ERβ in the mitochondria of ERβ knockdown cells reversed their sensitivity to cisplatin. Overall, our results demonstrate a ligand-independent role of ERβ in regulating apoptosis, revealing a novel function for ERβ in the mitochondria.
Secondary care treatment of patients with varicose veins in National Health Service England: at least how it appeared on a National Health Service website
Authors: Lim C S , Gohel M S , Shepherd A C , Davies A H
Published: July 2010

Objectives

This study aimed to assess the trends and regional variations in secondary care treatment of patients with varicose veins in National Health Service (NHS) England based on data published by the Hospital Episode Statistics which was freely and readily available to the public and health-care policy-makers.

Methods

Hospital Episode Statistics data for patients being treated for varicose veins, and UK Statistics Authority population estimates in all 28 Strategic Health Authorities (SHAs) in England from 2002 to 2006 were retrieved and analysed.

Results

Between 2002 and 2006 there was a 20% overall reduction (46,190–37,135) in the total number of varicose vein procedures performed in NHS England per year. The number of varicose vein procedures performed per 100,000 population per year varied significantly across the SHAs ( P < 0.0001). Similarly, significant regional variations were also noted in the frequency of primary procedures of greater and small saphenous vein ( P < 0.0001). During this time, injection sclerotherapy was only performed in 15 (53.6%) SHAs. The annual proportion of varicose vein procedures performed as daycases had increased from 56% to 64% during the period.

Conclusion

From 2002 to 2006 there was an overall reduction in the total number of varicose vein procedures performed in NHS England with major regional variations.
The venous system of the pelvis: new nomenclature
Authors: Kachlik D , Pechacek V , Musil V , Baca V
Published: July 2010

The clinical venous anatomy of the pelvis and its veins featured a break-through during the past few years. Not only the diagnostic and therapeutical methods but also the knowledge of the functional anatomy and nomenclatures of the veins underwent substantial changes. Eleven years ago, the most recent revision of the Latin anatomical nomenclature, Terminologia Anatomica (TA, 1998) was issued. In 2004, during the 21st World Congress of the International Union of Angiology, a consensus document (under the auspices of Federative International Committee on Anatomical Terminology and International Federation of Associations of Anatomists), reflecting phlebologists' requests for new terms and replacing several insufficient ones, was accepted. Six new terms were added in both Latin and English languages in the chapter concerning the veins of the pelvis. Eponyms are not considered equal synonyms and moreover only one of them was recommended for general use. Detailed anatomy of the veins of the pelvis is discussed. This consensus document will be incorporated in the next version of the Teminologia Anatomica.
The roles of phospholipase C activation and alternative ADAR1 and ADAR2 pre-mRNA splicing in modulating serotonin 2C-receptor editing in vivo
Authors: Schmauss Claudia , Zimnisky Ross , Mehta Mukti , Shapiro Lauren P.
Published: July 2010

The serotonin 2C receptor (5-HT2CR), a Gq-protein-coupled neurotransmitter receptor, exists in multiple isoforms that result from RNA editing of five exonic adenosines that are converted to inosines. In the adult brain, editing of 5-HT2C pre-mRNA exhibits remarkable plasticity in response to environmental and neurochemical stimuli. Here, we investigated two potential mechanisms underlying these plastic changes in adult 5-HT2CR editing phenotypes in vivo: activation of phospholipase C (PLC) and alternative splicing of pre-mRNA encoding the editing enzymes ADAR1 and ADAR2. Studies on two inbred strains of mice (C57Bl/6 and Balb/c) revealed that sustained stimulation of PLC—a downstream effector of activated Gαq protein—increased editing of forebrain neocortical 5-HT2C pre-mRNA at two sites known to be targeted by ADAR2. Moreover, changes in relative expression of the alternatively spliced “a” and “b” mRNA isoforms of ADAR1 and ADAR2 also correlate with changes in 5-HT2CR editing. The site-specific changes in 5-HT2CR editing detected in mice with different “a” over “b” ADAR mRNA isoform ratios only partially overlap with those evoked by sustained PLC activation and are best explained by the increased editing efficiency of ADAR1. Thus, activation of PLC and alternative splicing of ADAR pre-mRNA have both overlapping and specific roles in modulating 5-HT2CR editing phenotypes.
Does a Manufacturer Benefit from Selling to a Better-Forecasting Retailer?
Authors: Taylor Terry A. , Xiao Wenqiang
Published: July 2010

This paper considers a manufacturer selling to a newsvendor retailer that possesses superior demand-forecast information. We show that the manufacturer's expected profit is convex in the retailer's forecasting accuracy: The manufacturer benefits from selling to a better-forecasting retailer if and only if the retailer is already a good forecaster. If the retailer has poor forecasting capabilities, then the manufacturer is hurt as the retailer's forecasting capability improves. More generally, the manufacturer tends to be hurt (benefit) by improved retailer forecasting capabilities if the product economics are lucrative (poor). Finally, the optimal procurement contract is a quantity discount contract.
A comparison of two‐stage procedures for testing least‐squares coefficients under heteroscedasticity
Authors: Ng Marie , Wilcox Rand R.
Published: July 2010

This study explores the performance of several two‐stage procedures for testing ordinary least‐squares (OLS) coefficients under heteroscedasticity. A test of the usual homoscedasticity assumption is carried out in the first stage of the procedure. Subsequently, a test of the regression coefficients is chosen and performed in the second stage. Three recently developed methods for detecting heteroscedasticity are examined. In addition, three heteroscedastic robust tests of OLS coefficients are considered. A major finding is that performing a test of heteroscedasticity prior to applying a heteroscedastic robust test can lead to poor control over Type I errors.
Behavioural precursors of attachment representations in middle childhood and links with child social adaptation
Authors: Bureau Jean‐François , Moss Ellen
Published: July 2010

Concordance between age‐6 attachment behaviour and age‐8 doll play attachment representations during the school‐age period, and associations between these measures and child social adaptation at school were examined. One hundred and twenty‐nine 6‐year‐olds and their mothers participated in a separation/reunion protocol. Two years later, 104 children completed a doll play narrative task. Teachers evaluated child behaviour problems and prosocial behaviour at both ages. Results showed a significant four‐way concordance between age‐6 attachment behaviour and age‐8 doll play classifications. Each of the four attachment classifications was concordant in the absence of major negative life‐events, but only the disorganized classifications remained concordant when at least one negative life‐event occurred between the two assessment times. Children with a disorganized attachment classification or representation had higher externalizing scores than secure and avoidant children at both timepoints. Finally, the avoidant and disorganized behavioural classifications predicted avoidant and disorganized representations, respectively, even when controlling for age‐6 teacher reports of social adaptation.
The Journey of a Historian
Authors: Delumeau Jean
Published: July 2010

Distinguished historian Jean Delumeau describes the memorable influences and experiences over the course of his long career, including mentors, research directions, central themes of Christianization and dechristianization, major publications and their reception, and teaching emphases.
From Patriotism to Pluralism: How Catholics Initiated the Repeal of Birth Control Restrictions in Massachusetts
Authors: Meehan Seth
Published: July 2010

In 1948, Massachusetts Catholics, led by Archbishop Richard Cushing, successfully campaigned against a voter referendum that would have repealed the state’s law prohibiting the dissemination of birth control devices and information. Seventeen years later, however, Cushing, now a cardinal, did not oppose the next attempt to repeal the law. This article shows why and how Massachusetts Catholics (lay and clerical) changed their position on the limitations to birth control, the final restrictions in the country. They adopted a pluralistic language of religious tolerance with the help of John Courtney Murray, as he was drafting the Declaration on Religious Freedom.
Discretionary Subjects: Decision and Participation in William Gibson’s Fiction
Authors: Tobeck Janine
Published: July 2010

This comparison of protagonists in William Gibson’s “Johnny Mnemonic” and Pattern Recognition tests whether plot-driven fiction can produce only one type of literary subjectivity, or whether the subject can be successfully reimagined without abandoning the familiar narrative form. Contextualizing Gibson’s fiction with Alan Turing’s work on mathematical decidability, this essay explores the possibility of affecting radical change in understandings of identity while still appealing to a typical audience. Negotiating between the anti-sentimental modernist critique of personality and the democratic reach of conventional realism, Gibson’s work culls out a positive direction for thought about the potential of posthuman ethics.