tbuckley/cabot-search huggingface dataset:
Serum gastrin-releasing peptide levels correlate with disease severity and pruritus in patients with atopic dermatitis
Authors: A. Tirado-Sánchez, A. Bonifaz, R.M. Ponce-Olivera
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Pruritus results from the activation of small nerve endings in the skin by noxious mediators. Gastrin‐releasing peptide (GRP), substance P and glutamate have key roles in histamine‐dependent itch transmission. GRP is present in primary afferent nerve fibres and was found to be increased in mice with chronic dermatitis and pruritus.1 Therefore, GRP‐expressing nerves have an important role in mediating itch in animal models. Atopic dermatitis (AD) is a chronic, pruritic skin disease characterized by high serum IgE levels, positive immediate hypersensitivity to food or environmental allergens, and peripheral blood eosinophilia. The pathophysiology of itch in AD remains unclear; however, it can be explained by different mechanisms such as polarization of T helper 2 cells, proinflammatory cytokines (interleukins 31 and 33), abnormalities in the skin barrier (increased transepidermal water loss) and decreased skin hydration.2 3 Recently, Kagami et al.4 demonstrate that serum GRP levels were increased in patients with AD compared with healthy controls, and were significantly correlated with pruritus severity. Therefore, the potential role of GRP in the severity of AD was evaluated in the present study.
Factors associated with unknown aetiology in patients with community-acquired pneumonia
Authors: S. Ewig, A. Torres, M. Ángeles Marcos, J. Angrill, A. Rañó, A. de Roux, J. Mensa, J.A. Martínez, J.P. de la Bellacasa, T. Bauer
Journal: European Respiratory Journal (2002)

Despite comprehensive diagnostic work-up, the aetiology of community-acquired pneumonia (CAP) remains undetermined in 30–60% of cases. The authors studied factors associated with undiagnosed pneumonia. Patients hospitalised with CAP and being evaluated by two blood cultures, at least one valid lower respiratory tract sample, and serology on admission were prospectively recorded. Patients who had received antimicrobial pretreatment were excluded. Patients with definite or probable aetiology were compared to those with undetermined aetiology by uni- and multivariable analysis. A total 204 patients were eligible for the study. The aetiology remained undetermined in 82 (40%) patients, whereas a definite aetiology could be established in 89 (44%) and a probable one in 33 (16%). In multivariable analysis, factors associated with undetermined aetiology included age &gt;70 yrs, renal and cardiac comorbidity, and nonalveolar infiltrates on the chest radiograph. There was no association of undiagnosed pneumonia with mortality. Age and host factors were associated with unknown aetiology of community-acquired pneumonia. Some of these cases may also represent fluid volume overload mimicking pneumonia.
High-Risk Human Papillomavirus Affects Prognosis in Patients With Surgically Treated Oropharyngeal Squamous Cell Carcinoma
Authors: Lisa Licitra, Federica Perrone, Paolo Bossi, Simona Suardi, Luigi Mariani, Raffaella Artusi, Maria Oggionni, Chiara Rossini, Giulio Cantù, Massimo Squadrelli, Pasquale Quattrone, Laura D. Locati, Cristiana Bergamini, Patrizia Olmi, Marco A. Pierotti, Silvana Pilotti
Journal: Journal of Clinical Oncology (2006)

Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear.To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery.Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves.Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.
Correlations between nailfold microangiopathy severity, finger dermal thickness and fingertip blood perfusion in systemic sclerosis patients
Authors: A Sulli, B Ruaro, E Alessandri, C Pizzorni, M A Cimmino, G Zampogna, M Gallo, M Cutolo
Journal: Annals of the Rheumatic Diseases (2013)

The aim of this study was to identify possible correlations between nailfold microangiopathy severity, finger dermal thickness (DT) and fingertip blood perfusion (FBP) in systemic sclerosis (SSc) patients.Fifty-seven SSc patients and 37 healthy subjects were enrolled. All patients were evaluated by nailfold videocapillaroscopy (NVC) to classify and score the severity of microangiopathy. Both modified Rodnan skin score (mRss) and skin high-frequency ultrasound were used to detect finger DT. Laser Doppler flowmetry (LDF) was employed to detect FBP.A positive correlation was found between nailfold microvascular damage severity and both ultrasound-DT (p=0.028) and mRss values (p<0.0001). In particular, both ultrasound-DT and mRss were found progressively higher in patients with 'Early', 'Active' or 'Late' NVC pattern of microangiopathy. A negative correlation was observed between nailfold microvascular damage severity and FBP (p<0.0001), showing the lowest FBP of the patients with more advanced NVC patterns. A negative correlation was observed between FBP, and both ultrasound-DT (p=0.007) and mRss values (p=0.0002). SSc patients showed a higher ultrasound-DT at the level of the fingers, as well as a lower FBP than healthy subjects (p<0.0001).This study demonstrates a relationship between nailfold microangiopathy severity, DT and FBP in SSc patients.
Early Disaster Response in Haiti: The Israeli Field Hospital Experience
Authors: Yitshak Kreiss
Journal: Annals of Internal Medicine (2010)

The earthquake that struck Haiti in January 2010 caused an estimated 230 000 deaths and injured approximately 250 000 people. The Israel Defense Forces Medical Corps Field Hospital was fully operational on site only 89 hours after the earthquake struck and was capable of providing sophisticated medical care. During the 10 days the hospital was operational, its staff treated 1111 patients, hospitalized 737 patients, and performed 244 operations on 203 patients. The field hospital also served as a referral center for medical teams from other countries that were deployed in the surrounding areas. The key factor that enabled rapid response during the early phase of the disaster from a distance of 6000 miles was a well-prepared and trained medical unit maintained on continuous alert. The prompt deployment of advanced-capability field hospitals is essential in disaster relief, especially in countries with minimal medical infrastructure. The changing medical requirements of people in an earthquake zone dictate that field hospitals be designed to operate with maximum flexibility and versatility regarding triage, staff positioning, treatment priorities, and hospitalization policies. Early coordination with local administrative bodies is indispensable.
The Athlete Biological Passport: an integral element of innovative strategies in antidoping
Authors: Alan R Vernec
Journal: British Journal of Sports Medicine (2014)

Concern for the health of athletes and integrity of sport resulted in the banning of specific substances although many years passed before analytical testing took place. Soon doping control programmes became synonymous with urine tests and adverse analytical findings. This system has its limits due to the detection window of prohibited substances, the timing of sample collections and the sophistication of some doping regimens. There have been a number of situations where these limits were demonstrated by athletes who proclaimed innocence based on passing their analytical tests only to later confess to doping. New strategies were called for to protect clean athletes. In the current World Anti-Doping Code, there are eight means to an Anti-Doping Rule Violation (ADRV). Article 2.2 states that the use of a prohibited substance may be established by any reliable means including witness statements, documentary evidence or evaluations of longitudinal profiling. In 2006, the World Anti-Doping Agency (WADA) with the support of some International Federations (IFs) gathered a group of experts to develop a harmonised programme on longitudinal profiling, or serial analysis of indirect biomarkers of doping, that was both scientifically and legally robust. This culminated in the WADA Athlete Biological Passport (ABP) Operating Guidelines and Technical Documents, published in 2009. The ABP is a paradigm that infers the use of prohibited substance (or method) by the monitoring of discriminant biomarkers over time. The haematological module detects blood manipulation by the use of erythropoietic stimulating agents or via blood transfusions. The steroidal module aims to identify endogenous anabolic androgenic steroids when administered exogenously and other indirect steroid doping substances or methods. Other ABP modules (endocrine, 'omics') are being developed. The term passport, first coined in 2000, is now defined in the ABP Guidelines as the longitudinal profile and all other relevant information including training, competitions and information derived from investigations. In the 2015 World Anti-Doping Code, investigations or enquiries gathered from other sources will play an even more prominent role.
Multiple Roles for the Receptor Tyrosine Kinase Axl in Tumor Formation
Authors: Sacha J. Holland, Mark J. Powell, Christian Franci, Emily W. Chan, Annabelle M. Friera, Robert E. Atchison, John McLaughlin, Susan E. Swift, Erlina S. Pali, George Yam, Stephen Wong, Joe Lasaga, Mary R. Shen, Simon Yu, Weiduan Xu, Yasumichi Hitoshi, Jakob Bogenberger, Jacques E. Nör, Donald G. Payan, James B. Lorens
Journal: Cancer Research (2005)

Abstract A focus of contemporary cancer therapeutic development is the targeting of both the transformed cell and the supporting cellular microenvironment. Cell migration is a fundamental cellular behavior required for the complex interplay between multiple cell types necessary for tumor development. We therefore developed a novel retroviral-based screening technology in primary human endothelial cells to discover genes that control cell migration. We identified the receptor tyrosine kinase Axl as a novel regulator of endothelial cell haptotactic migration towards the matrix factor vitronectin. Using small interfering RNA–mediated silencing and overexpression of wild-type or mutated receptor proteins, we show that Axl is a key regulator of multiple angiogenic behaviors including endothelial cell migration, proliferation, and tube formation in vitro. Moreover, using sustained, retrovirally delivered short hairpin RNA (shRNA) Axl knockdown, we show that Axl is necessary for in vivo angiogenesis in a mouse model. Furthermore, we show that Axl is also required for human breast carcinoma cells to form a tumor in vivo. These findings indicate that Axl regulates processes vital for both neovascularization and tumorigenesis. Disruption of Axl signaling using a small-molecule inhibitor will hence simultaneously affect both the tumor and stromal cell compartments and thus represents a unique approach for cancer therapeutic development.
Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer
Authors: Chandrakumar Shanmugam, Robert B Hines, Nirag C Jhala, Venkat R Katkoori, Bin Zhang, James A Posey, Harvey L Bumpers, William E Grizzle, Isam E Eltoum, Gene P Siegal, Upender Manne
Journal: Journal of Hematology & Oncology (2011)

Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.
P37 Platelet count and spleen size: avoidance of screening endoscopy for varices in patients with hepatitis C cirrhosis
Authors: J. Gerada, E. Gerada, S. Sen, W. J. Griffiths
Journal: Gut (2011)

<h3>Introduction</h3> Many patients with liver cirrhosis, screened for oesophageal varices (OV) are found to have either no or insignificant varices, resulting in unnecessary procedures and financial burden. We had previously shown that the non-invasive parameters of platelet count and spleen size, measured by transabdominal ultrasound, were highly sensitive for the prediction of OV in patients with hepatitis C cirrhosis. <h3>Aim</h3> To determine in a subsequent cohort of patients with hepatitis C cirrhosis whether such a clinical tool was accurate in determining which patients require endoscopic screening. <h3>Method</h3> 246 outpatients with biopsy-proven hepatitis C cirrhosis over a 3-year period were studied retrospectively. Endoscopy should have been performed, according to our protocol, if any of the following parameters were met: platelet count &lt;100×10<sup>9</sup>/l, spleen size _14 cm or specific ultrasound findings indicative of portal hypertension (recanalised paraumbilical vein, ascites, splenic hilar varices). <h3>Results</h3> Of 246 patients, 98 patients underwent upper GI endoscopy, 76 of whom met criteria (78%). Of 148 patients who did not undergo endoscopy, 63 met criteria (43%). Endoscopic findings are summarised in the Abstract P37 table 1 below. <h3>Conclusion</h3> Using simple non-invasive criteria, screening endoscopy could be avoided in around 44% of patients with hepatitis C cirrhosis. Treatable varices would not be missed in this group.
Dermatitis herpetiformis and cigarette smoking
Authors: J B SMITH, S B SMITH, J J ZONE
Journal: Gut (1998)

Dermatitis herpetiformis and cigarette smokingEDITOR,-Some time ago a study by Snook and colleagues (Gut 1996;39:60-2) found cigarette smoking to be less prevalent among those with coeliac disease.This prompted Lear and colleagues (Gut 1997;40:289) to evaluate smoking status in patients with dermatitis herpetiformis (DH), an autoimmune blistering skin disease that also presents with a gluten sensitive enteropathy.They found that 29 patients with DH were significantly less likely to be smokers than matched and unmatched controls.As we also have a large population of patients with DH, we did a preliminary review of our existing database to evaluate smoking status in these patients.A review of over 200 patient charts with biopsy confirmed DH (granular IgA in papillary dermis) revealed smoking information on 105 patients.Fifteen of these patients were less than 20 years of age at disease onset and thus were eliminated from the study, leaving 90 evaluable patients.Of these patients eight (8.9%) were smokers, whereas 17.1% of the Utah population aged 20 years or older are smokers, 1 thus confirming the findings of Lear et al that patients with DH are less likely to be smokers than those in the general population.The reasons for this finding are not fully clear.It is well known that cigarette smoking adversely aVects the skin, although a few conditions have been reported where smoking may have a beneficial eVect. 2 Likewise, when it comes to the gastrointestinal tract, smoking may have adverse eVects in the case of Crohn's disease, yet beneficial eVects in ulcerative colitis. 3 How do we explain this apparent beneficial eVect of smoking when it comes to DH?It is likely that the immunosuppressive eVects of smoking play a role in this autoimmune disease, yet there are other autoimmune skin diseases, such as psoriasis, which are made worse and not better by smoking. 4One study found decreased serum IgA in smokers which may also play a role. 5Finally, the well known vasoconstrictive eVects of nicotine could play a role at least in the cutaneous manifestations of DH.As we found our DH patients more likely to be non-smokers, does this mean that if they take up the habit their DH will go away or even improve?We don't know, but it seems unlikely.We also doubt our institutional review board would ever approve a study to find out.This study was a preliminary review and does not prove that being a non-smoker is a risk factor for DH.It may be only one variable of the equation, and other likely much more important confounding factors such as genetics and other environmental factors play a greater role.Further more complete studies are needed to confirm our finding.
Potassium citrate/citric acid intake improves renal function in rats with polycystic kidney disease.
Authors: G A Tanner
Journal: Journal of the American Society of Nephrology (1998)

Polycystic kidney disease (PKD) has been shown to be exacerbated by acidosis or a low potassium intake, and there is evidence that administration of alkali might have a beneficial effect. This study determined whether ingestion of potassium citrate and citric acid would ameliorate PKD. Healthy normal and heterozygous littermate Han:SPRD rats with autosomal dominant PKD were provided with either tap water or 55 mM K3citrate/67 mM citric acid solution (KCitr) to drink starting at the age of 1 mo. Renal clearance measurements and histologic assessments were performed when the rats were 3 mo old. KCitr intake did not affect body weight or urine flow, but completely prevented the decline in GFR found in untreated rats with PKD. In rats that drank tap water, left kidney GFR averaged (in microliter/min per 100 g body wt) 503 +/- 78 (n = 9) in normal animals and 242 +/- 56 (n = 6) in rats with PKD. In rats that drank KCitr, GFR averaged 562 +/- 123 (n = 7) in normal animals and 534 +/- 103 (n = 7) in rats with PKD. Kidneys of rats with PKD were approximately double normal size. KCitr treatment did not affect kidney size, but led to fewer interstitial abnormalities and smaller cysts in cystic kidneys. KCitr ingestion led to a significantly lower (P < 0.001) plasma [K+] in rats with PKD (3.3 +/- 0.2 versus 4.1 +/- 0.2 mEq/L in rats on tap water). Chronic KCitr intake in the young heterozygous Han:SPRD rat with PKD yields a modest improvement of kidney histology and a dramatic improvement in GFR. The mechanism of action of KCitr and the long-term effects of this treatment on renal structure and function in PKD deserve further study.
Initial events in psoriasis: quantitative assessment*
Authors: E. CHRISTOPHERS, R PARZEFALL, O. BRAUN-FALCO
Journal: British Journal of Dermatology (2006)

Seven 3H-TdR-labelled early psoriatic lesions were quantitatively evaluated after serial sectioning and autoradiography. Epidermal thickness was measured planimetrically, whereas labelled cells as well as the number of nuclei present in the dermis were counted. Marked differences in the number of labelled cells as well as in their grain density were observed. These differences correlated with the density of the dermal infiltrate. It is concluded that psoriatic epidermal hyperplasia possibly develops as a response to antecedent and persisting events in the dermis.
Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques?
Authors: Jenny E. Kanter, Fredrik Johansson, Renee C. LeBoeuf, Karin E. Bornfeldt
Journal: Circulation Research (2007)

It is becoming increasingly clear that suboptimal blood glucose control results in adverse effects on large blood vessels, thereby accelerating atherosclerosis and cardiovascular disease, manifested as myocardial infarction, stroke, and peripheral vascular disease. Cardiovascular disease is accelerated by both type 1 and type 2 diabetes. In type 1 diabetes, hyperglycemia generally occurs in the absence of elevated blood lipid levels, whereas type 2 diabetes is frequently associated with dyslipidemia. In this review article, we discuss hyperglycemia versus hyperlipidemia as culprits in diabetes-accelerated atherosclerosis and cardiovascular disease, with emphasis on studies in mouse models and isolated vascular cells. Recent studies on LDL receptor-deficient mice that are hyperglycemic, but exhibit no marked dyslipidemia compared with nondiabetic controls, show that diabetes in the absence of diabetes-induced hyperlipidemia is associated with an accelerated formation of atherosclerotic lesions, similar to what is seen in fat-fed nondiabetic mice. These effects of diabetes are masked in severely dyslipidemic mice, suggesting that the effects of glucose and lipids on lesion initiation might be mediated by similar mechanisms. Recent evidence from isolated endothelial cells demonstrates that glucose and lipids can induce endothelial dysfunction through similar intracellular mechanisms. Analogous effects of glucose and lipids are also seen in macrophages. Furthermore, glucose exerts many of its cellular effects through lipid mediators. We propose that diabetes without associated dyslipidemia accelerates atherosclerosis by mechanisms that can also be activated by hyperlipidemia.