tbuckley/cabot-search huggingface dataset:
Anal carcinoma in human immunodeficiency virus-positive men: results of a prospective study from Germany
Authors: A. Kreuter, A. Potthoff, N.H. Brockmeyer, T. Gambichler, J. Swoboda, M. Stücker, M. Schmitt, H. Pfister, U. Wieland
Journal: British Journal of Dermatology (2010)

Background Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). There is a paucity of data published on the progression of high-grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma. Objectives To search for anal carcinoma and AIN in a large series of HIV-positive MSM, to assess treatment response of anal carcinoma, and to analyse lesional HPV spectrum of anal cancers. Methods Detection of anal carcinoma and AIN was performed using cytology, high-resolution anoscopy, and histology in case of abnormal findings. Additionally, HPV analyses for 36 high- and low-risk α-HPV types were performed in patients with anal carcinoma. Results In total, 446 German HIV-positive MSM were examined within an observation period of 5 years and 10 months. Of these, 116 (26·0%) patients had normal findings, 163 (36·5%) had low-grade AIN, 156 (35·0%) had high-grade AIN, and 11 (2·5%) had anal carcinoma as evidenced by the highest grade of cytology/histology. Five patients with anal cancer, who had refused treatment of their precancerous lesions, had progressed from high-grade AIN to invasive cancer within a median time of 8·6 months. All anal cancers carried high-risk α-HPV types. All five squamous cell carcinomas (SCCs) of the anal canal were HPV16 positive. In contrast, only one of the four anal margin SCCs were HPV16 positive (HPV31, HPV33 and HPV33 + HPV68 were found in the other three anal margin SCCs). HPV59 was found in two adenocarcinomas, one of which additionally carried HPV33. In contrast to the cancer biopsies, a broad spectrum of surface high- and low-risk HPV types was found in anal swabs of the patients. Surgical excision resulted in long-term disease control of all anal margin carcinomas, whereas combined chemoradiotherapy in carcinomas of the anal canal was associated with high recurrence rates, high toxicity, and high mortality. Conclusions Anal carcinoma and AIN are frequent in HIV-positive men, even in patients participating in anal cancer prevention programmes. High-grade dysplasia in these patients can progress to invasive cancer within a short period of time. Anal margin carcinoma and anal canal carcinoma differ substantially in their lesional HPV spectrum, prognosis and treatment response.
Dynamic Ventricular Dyssynchrony
Authors: Stephane Lafitte, Pierre Bordachar, Marianne Lafitte, Stephane Garrigue, Sylvain Reuter, Patricia Reant, Karim Serri, Valerie Lebouffos, Marianne Berrhouet, Pierre Jais, Michel Haissaguerre, Jacques Clementy, Raymond Roudaut, Anthony N. DeMaria
Journal: Journal of the American College of Cardiology (2006)
Evaluation of continuous positive airway pressure compliance in a group of obstructive sleep apnea patients
Authors: Nasr Affara, Hany Shaarawy
Journal: European Respiratory Journal (2012)

Currently, the treatment of choice for OSA is nasal CPAP but the documented efficacy of CPAP may be poor because of decreased compliance.  Objective  is to evaluate the CPAP compliance in a group of OSA patients in the state of Kuwait.  Methods:  60 patients proved to have OSA by polysomnography, (ESS) and (FOSQ) were done for all patients then follow up for 3 months were done and then patients reassessed again.  Results : Only 45 patients (75%) were compliant on CPAP with a mean runtime of 5.23 ± 0.46 hour / night, CPAP significantly improved the AHI from 44.89± 10.85 to 5.93± 1.68 / hour, ESS from 12.88 ± 2.32 to 3.47 ± 1.14 and total FOSQ from 83.78 ± 1.67 to 108.39 ± 1.40(p  Conclusion:  in this group of patients the rate of CPAP compliance was considered good (75%) and the only factors that can predict short term CPAP compliance were the BMI and ESS.  Key words: OSA, CPAP compliance, ESS, FOSQ.
Phase II trial of chlorozotocin and fluorouracil in islet cell carcinoma: a Southwest Oncology Group study.
Authors: R M Bukowski, C Tangen, R Lee, J S Macdonald, A B Einstein, R Peterson, T R Fleming
Journal: Journal of Clinical Oncology (1992)

PURPOSE A phase II trial that used fluorouracil (5-FU) and chlorozotocin (CTZ) was performed in patients with metastatic islet cell carcinoma to determine the response rate and toxicity. PATIENTS AND METHODS Patients received four cycles of induction chemotherapy. Good-risk patients received 5-FU 800 mg/m2/d days 1 to 4 as a continuous intravenous (IV) infusion (CIV) and CTZ 175 mg/m2 IV on day 1. Poor-risk patients (previous radiation to &gt; or = 25% bone marrow-bearing areas; serum bilirubin &gt; or = 5 mg/dL; creatinine &gt; 1.0 mg/dL) received 5-FU 600 mg/m2/d and CTZ 75 mg/m2 in a similar manner. In responding or stable patients, reduced doses of 5-FU and CTZ were continued as maintenance therapy (maximum, 18 months). RESULTS Forty-seven of 51 patients were eligible, and 44 received chemotherapy. Fourteen of 44 patients had partial responses, with 13 of 36 (36%; 95% confidence interval [CI], 21.0% to 54.0%) good-risk patients and one of eight (12%; 95% CI, 0.3 to 52.6%) poor-risk patients responding. Median survival of all patients was 25 months, and the median response duration was 11 months. Side effects were moderate to severe and included myelosuppression and gastrointestinal toxicity. Thirteen patients developed renal toxicity, which was severe or life-threatening in five. This seemed to be related to the administration of cumulative doses of CTZ &gt; or = 1,500 mg. CONCLUSION These results demonstrate that the combination of 5-FU and CTZ has activity in islet cell carcinoma, but the occurrence of renal toxicity secondary to CTZ may limit the use of this agent.
Quantitation of Lymphocytes and T-Cell Subsets in Patients With Disseminated Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M A Cobleigh, D P Braun, J E Harris
Journal: JNCI Journal of the National Cancer Institute (1980)

Human peripheral blood T-cells were divided into subsets on the basis of their ability to bind to the Fc receptor portion of IgG (TG cells) or IgM (TM cells). These subsets were studied in 25 patients with newly diagnosed disseminated malignant solid tumors. When compared to a group of healthy, agematched controls, cancer patients as a group exhibited significantly increased percentages of TG cells and significantly decreased percentages and numbers of TM cells. Comparison of the values determined for individual patients to those determined for groups of 10 healthy individuals in the same decade of life revealed that most cancer patients had normal levels of lymphocytes and T-cells, but many had aberrant values for T-cell subsets.
Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer.
Authors: D C Smith, R L Dunn, M S Strawderman, K J Pienta
Journal: Journal of Clinical Oncology (1998)

PURPOSE Prostate-specific antigen (PSA) has been used as a marker of advanced prostate cancer but remains controversial. To evaluate PSA as a predictor of survival, we analyzed data from sequential phase II trials of estramustine and etoposide. METHODS A landmark analysis that used data from 62 men with PSA levels at baseline and 8 weeks was conducted. The best PSA measure (of six evaluated) was incorporated into a multiple regression model with performance status (PS); relative change in PSA level; and pretreatment PSA, alkaline phosphatase, and hemoglobin values. RESULTS A decrease in PSA of 50% or greater at 8 weeks was associated with a significantly increased survival (P=.0005, two-sided log-rank test). Median survival from the landmark was 91 weeks in patients with a 50% or greater decrease at 8 weeks versus 38 weeks in those without this decrease. Modeling showed that PS, pretreatment hemoglobin level, and relative change in PSA level were significant prognostic factors, with a significant interaction between PS and pretreatment hemoglobin level. In the final model, a relative change in PSA level at 8 weeks of less than 50% had an adjusted relative risk of 2.20 (95% confidence interval, 1.21 to 4.00). A decrease in PSA level of 50% or greater at any time during therapy was associated with a response in measurable disease (P=.0369, two-sided Fisher's exact test). CONCLUSION The PSA value after 8 weeks of this cytotoxic regimen does predict survival. A decrease in PSA level is associated with both survival and response in soft tissue lesions and should be incorporated into the response criteria and reporting of trials of cytotoxic agents in prostate cancer.
siRNA Lipid Nanoparticle Potently Silences Clusterin and Delays Progression When Combined with Androgen Receptor Cotargeting in Enzalutamide-Resistant Prostate Cancer
Authors: Yoshiaki Yamamoto, Paulo J.C. Lin, Eliana Beraldi, Fan Zhang, Yoshihisa Kawai, Jeffrey Leong, Hidemasa Katsumi, Ladan Fazli, Robert Fraser, Pieter R. Cullis, Martin Gleave
Journal: Clinical Cancer Research (2015)

Lipid nanoparticle (LNP) formulations facilitate tumor uptake and intracellular processing through an enhanced permeation and retention effect (EPR), and currently multiple products are undergoing clinical evaluation. Clusterin (CLU) is a cytoprotective chaperone induced by androgen receptor (AR) pathway inhibition to facilitate adaptive survival pathway signaling and treatment resistance. In our study, we investigated the efficacy of siRNA tumor delivery using LNP systems in an enzalutamide-resistant (ENZ-R) castration-resistant prostate cancer (CRPC) model.Gene silencing of a luciferase reporter gene in the PC-3M-luc stable cell line was first assessed in subcutaneous and metastatic PC-3 xenograft tumors. Upon validation, the effect of LNP siRNA targeting CLU in combination with AR antisense oligonucleotides (ASO) was assessed in ENZ-R CRPC LNCaP in vitro and in vivo models.LNP LUC-siRNA silenced luciferase expression in PC-3M-luc subcutaneous xenograft and metastatic models. LNP CLU-siRNA potently suppressed CLU and AR ASO-induced CLU and AKT and ERK phosphorylation in ENZ-R LNCaP cells in vitro, more potently inhibiting ENZ-R cell growth rates and increased apoptosis when compared with AR-ASO monotherapy. In subcutaneous ENZ-R LNCaP xenografts, combinatory treatment of LNP CLU-siRNA plus AR-ASO significantly suppressed tumor growth and serum PSA levels compared with LNP LUC-siRNA (control) and AR-ASO.LNP siRNA can silence target genes in vivo and enable inhibition of traditionally non-druggable genes like CLU and other promising cotargeting approaches in ENZ-R CRPC therapeutics.
Is There an Allergic Synovitis?
Authors: D N Golding
Journal: Journal of the Royal Society of Medicine (1990)

Nine patients had attacks of joint pain and sometimes swelling precipitated by certain foods or associated with allergic manifestations. All were atopic subjects-three having strong evidence of Type I (immediate) allergy and three ‘urticarial arthralgia’, in which attacks of severe urticaria and joint pain occurred coincidentally. Food allergy appeared to be responsible for the joint symptoms in three patients and in one it was possible to precipitate swelling of a knee due to synovitis with effusion by drinking milk a few hours beforehand, the synovial fluid having mildly inflammatory features and a relatively high eosinophil count. It seems that allergy is an occasional cause of episodic rheumatic pain or synovitis in certain atopic patients, whether or not they have an underlying arthritis. These are usually Type I hypersensitivity reactions, though it is thought that some food-allergic reactions are immune complex-mediated.
Exceptional cheeses can be made only from raw milk
Authors: A. Cunynghame
Journal: BMJ (1996)

products....Although Stalin had a sophisticated propaganda machine for its time, the tobacco industry is using the most advanced technology available to produce a 21st-century propaganda effort.Stalin's methods were perceived as cold and calculating, but those of the tobacco industry are smooth and subtle.The marketing plans are prospective, with the result of pervasively infiltrating all facets of Russian life."2I find Hurt's analogy entirely apt, and I urge Cambridge most earnestly to deny BAT an honour which will lower the esteem in which Cambridge is held throughout the world.
Indian paediatricians ask government to add mumps vaccine to immunisation programme
Authors: Ganapati Mudur
Journal: BMJ (2015)

The Indian Academy of Paediatrics has asked India’s health ministry to add the mumps vaccine to the free childhood immunisation programme, saying that this viral infection is a serious public health concern. 

In a position paper the academy asked the health ministry to add the mumps vaccine to those of measles and rubella, citing the government’s own disease surveillance data and 14 peer reviewed publications as evidence for the widespread prevalence of mumps.1

The health ministry’s integrated disease surveillance programme investigated 72 outbreaks of mumps over a five year period, from September 2009 to November 2014, with a total of …
Pretreatment with inhaled procaterol improves symptoms of dyspnea and quality of life in patients with severe COPD
Authors: Hiroyuki Ohbayashi, Mitsuru Adachi
Journal: European Respiratory Journal (2012)

Objectives:  To investigate the efficacy of the inhaled supplementary short-acting beta2-agonists (SABA) administered before the performance of daily activity (the SABA Assust Use) in patients with COPD.  Methods:  Thirty outpatients with moderate to severe COPD (Stage II - IV), regular use of tiotropium bromide alone, and dyspnea during daily activities, were enrolled. Subjects self-administered 20μg of inhaled procaterol hydrochloride before daily activities no more than four times daily. Dyspnea symptom scores, St George9s Respiratory Questionnaire (SGRQ) activity domains, impulse oscillometry system parameters, and pulmonary function tests were recorded at the beginning and end of the 2-week study.  Results:  More than 80% of subjects reported dyspnea when performing the following activities: walking up a slope (100.0%), climbing stairs (100.0%), gardening (93.3%), walking on flat ground (90.0%), bathing (86.7%), getting on a bus or train (83.3%), and changing clothes (80.0%). After 2 weeks, subjects with Stage III significantly improved dyspnea scores (walking up a slope (p=0.047), climbing stairs (p=0.014), gardening (p=0.034), walking on flat ground (p=0.006), getting on a bus or train (p=0.039), and changing clothes (p=0.045)). Both symptoms and activity SGRQ domains significantly improved in subjects with Stage III (p=0.036 and p=0.028, respectively). Resistance of small airways (R5-R20) and low-frequency reactance area (AX) significantly improved in subjects with Stage III (p=0.003 and p=0.004, respectively). No significant changes were found in pulmonary function tests.  Conclusion:  The SABA Assist Use improved dyspnea symptoms in subjects with Stage III COPD.
Wnt11 inhibits effects of transforming growth factor-beta1 (TGFβ1) on lung epithelial phenotype
Authors: Rahul Mahida, Domokos Bartis, David Thickett
Journal: European Respiratory Journal (2013)

TGFβ1 induces epithelial-mesenchymal transition (EMT) in alveolar type 2 cells in vitro & is implicated in idiopathic pulmonary fibrosis (IPF). Wnt11 is secreted by the lung mesenchyme. Literature suggests that Wnt signalling has crosstalk with the TGFβ1 signalling pathway & may play a role in IPF pathogenesis. There are currently no data on Wnt11 function in adult lungs; we investigated its putative role in EMT.  A549 cells were treated with 10ng/ml TGFβ1 for 24 hours. We developed transgenic A549 cells which stably overexpress Wnt11. Mesenchymal marker expression (N-Cadherin, SLUG, Vimentin, α-Smooth Muscle Actin) were assessed using RT-qPCR. BrdU proliferation assays & wound healing assays were performed using these cells. Confocal microscopy was used to observe intracellular SMAD distribution.  Following TGFβ1 treatment, A549-Wnt11 cells had reduced relative mRNA expression of mesenchymal markers compared with normal A549 cells. Using confocal microscopy SMAD was detected in nuclei of normal A549 cells, but not in nuclei of A549-Wnt11 cells, indicating inhibition of SMAD translocation to the nucleus. Wnt11 significantly inhibited A549 cell motility on wound healing assays (P=0.037) & significantly enhanced A549 cell proliferation on proliferation assays (P=0.0014).  Wnt11 appears to inhibit TGFβ1 mediated EMT in A549 cells, & inhibits epithelial wound repair which is abnormal in IPF.
Brief Communication: Foreign-Body Tumorigenesis by Vinyl Chloride Vinyl Acetate Copolymer: No Evidence for Chemical Cocarcinogenesis2
Authors: K. Gerhard Brand, Lance C. Buoen, Inge Brand
Journal: JNCI Journal of the National Cancer Institute (1975)

We investigated whether vinyl chloride monomers, released from implants of vinyl chloride vinyl acetate copolymer (VCA), exerted cocarcinogenic activity and added thereby to the mechanism of foreign-body (FB) tumorigenesis. CBA/H and CBA/H-T6 mice were used. No evidence was found to indicate that chemical carcinogenic activity partakes in tumorigenesis by VCA implants. Hence it was concluded that VCA plastic is not suitable for the study of the combined process of FBI chemical cocarcinogenesis. Furthermore, experimental results obtained with VCA film implants were representative of FB tumorigenesis in the absence of demonstrable chemical carcinogenic activity.
Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. 1962.
Authors: F C Bartter, P Pronove, J R Gill, R C MacCardle
Journal: Journal of the American Society of Nephrology (1998)

A new syndrome, characterized by hypertrophy and hyperplasia of the juxtaglomerular apparatus of the kidneys, aldosteronism resulting from adrenal cortical hyperplasia, and persistently normal blood pressure is described in two patients. Overproduction of aldosterone could not be prevented by sodium loading or by administration of albumin intravenously; it was associated with hypokalemic alkalosis and Pitressin-resistant impairment of urinary concentrating ability. In both subjects, increased amounts of circulating angiotensin were demonstrated; infusion of angiotensin II produced rises of blood pressure in both subjects considerably less than the rises induced by comparable doses in normal subjects. The sequence of events, (1) primary resistance to the pressor action of angiotensin, (2) compensatory overproduction of renin and thus of angiotensin, and (3) stimulation of adrenal cortex by angiotensin is consistent with all the information available about the syndrome.
The effects of non-invasive bilevel positive airway pressure ventilation on insulin resistance in patients with obstructive sleep apnea
Authors: Ognian Georgiev, Daniela Petrova, Radoslav Bilyukov, Tzanko Mondeshki
Journal: European Respiratory Journal (2011)

Background:  The effects of the noninvasive ventilation on insulin resistance in obstructive sleep apnea (OSA) patients has been elusive. Although there are a lot of trials concerning its effectiveness, data is still conflicting. There is a lack of studies dealing with the results of the bilevel positive airway pressure (BiPAP) therapy.   Materials and methods:  Thirteen patients with type 2 diabetes and eighteen with insulin resistance and newly diagnosed OSA (AHI>30) received BiPAP therapy. Patients were followed up for a mean period of 3,9 months (±1,5) and had a compliance >80%. The average body mass index (BMI) was 38,17 and the mean AHI - 51,95. Baseline tests - blood glucose, HOMA-index, immunoreactive insulin (IRI), HbA1C were performed and repeated at the end of follow up.   Results:  Results are given as mean (±SD). Blood glucose measurements did not change significantly in none of the groups - type 2 diabetes (5,5mmol/l±1,8 vs. 5,46mmol/l ±2,01); insulin resistance (6,46mmol/l±1,16 vs. 6,01mmol/l ± 1,38). There was a more significant decrease of IRI and HOMA – index the insulin resistance group – (IRI-21.06±11,9vs. 14.46±10,1), (HOMA-index – 5,23±1,18 vs.3,47±3,12). In comparison the group with type 2 diabetes showed a lesser effect of BiPAP therapy (IRI-26,06±11 vs. 22,5±10.09), (HOMA-index – 7,7±4,6vs.6,01±2,7).Body mass index and waist circumference remained unchanged.   Conclusions:  BiPAP therapy reduced the insulin resistance in obese OSA patients. The effectiveness was better in patients with insulin resistance than those with already overt type 2 diabetes. HOMA- index seems to be the most sensitive marker for the effect of BiPAP therapy.
Reduced mortality in dermatitis herpetiformis: a population‐based study of 476 patients
Authors: K. Hervonen, A. Alakoski, T.T. Salmi, S. Helakorpi, H. Kautiainen, K. Kaukinen, E. Pukkala, P. Collin, T. Reunala
Journal: British Journal of Dermatology (2012)

Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease and most patients adhere to a life-long gluten free diet (GFD). Increased mortality rates have been reported in coeliac disease but knowledge in DH is scanty.To survey the mortality rate and causes of death in a large cohort of patients with DH.Patients with DH (n = 476 consecutive patients) diagnosed from 1970 onwards at the Tampere University Hospital were analysed for causes of death during 1971-2010. A questionnaire survey on key aspects of health behaviour was performed in patients with DH and comparisons were made with the Finnish population.The total number of deaths during 9079 person years followed up was 77 whereas 110 were expected. The standardized mortality rate (SMR) for all causes of death was significantly reduced, being 0·70 (95% CI 0·55-0·87), and similar in both sexes. The SMR was equal in the patients with DH with (0·73) and without (0·77) small bowel villous atrophy. The SMR was significantly reduced (0·38) for deaths due to cerebrovascular diseases. The SMR due to lymphoproliferative malignancies was significantly increased (6·86) in the first 5 years of follow-up but not thereafter. The questionnaire survey documented that 97·7% of the patients with DH adhered to a GFD. The patients reported significantly less hypercholesterolaemia and there were fewer current and past smokers compared with the age- and sex-matched control population.The present long-term follow-up study of DH documented significantly reduced all-cause and cerebrovascular disease mortality. Strict adherence to a GFD, less smoking and hypercholesterolaemia may play a role in the observed health benefit.
Abstract 2395: Elevated Serum Fibrin-Monomer Level is a Strong Predictor for the Long-Term Cerebrovascular Events in Patients with Acute Ischemic Stroke
Authors: Harutoshi Tamura, Osamu Hirono, Hidenobu Okuyama, Ling Liu, Satoshi Nishiyama, Takamasa Kayama, Isao Kubota
Journal: Circulation (2006)

Introduction Serum fibrin-monomer (FM), which is produced by the thrombin- mediated resolution of fibrinopeptide A from fibrinogen, is a new marker for systemic hypercoagulable state and thrombus f...