tbuckley/cabot-search huggingface dataset:
Coupling between annual and ENSO timescales in the malaria-climate association in Colombia.
Authors: G Poveda, W Rojas, M L Quiñones, I D Vélez, R I Mantilla, D Ruiz, J S Zuluaga, G L Rua
Journal: Environmental Health Perspectives (2001)

We present evidence that the El Niño phenomenon intensifies the annual cycle of malaria cases for Plasmodium vivax and Plasmodium falciparum in endemic areas of Colombia as a consequence of concomitant anomalies in the normal annual cycle of temperature and precipitation. We used simultaneous analyses of both variables at both timescales, as well as correlation and power spectral analyses of detailed spatial (municipal) and temporal (monthly) records. During "normal years," endemic malaria in rural Colombia exhibits a clear-cut "normal" annual cycle, which is tightly associated with prevalent climatic conditions, mainly mean temperature, precipitation, dew point, and river discharges. During historical El Niño events (interannual time scale), the timing of malaria outbreaks does not change from the annual cycle, but the number of cases intensifies. Such anomalies are associated with a consistent pattern of hydrological and climatic anomalies: increase in mean temperature, decrease in precipitation, increase in dew point, and decrease in river discharges, all of which favor malaria transmission. Such coupling explains why the effect appears stronger and more persistent during the second half of El Niño's year (0), and during the first half of the year (+1). We illustrate this finding with data for diverse localities in Buenaventura (on the Pacific coast) and Caucasia (along the Cauca river floodplain), but conclusions have been found valid for multiple localities throughout endemic regions of Colombia. The identified coupling between annual and interannual timescales in the climate-malaria system shed new light toward understanding the exact linkages between environmental, entomological, and epidemiological factors conductive to malaria outbreaks, and also imposes the coupling of those timescales in public health intervention programs.
Fecal Occult Blood Screening for Colorectal Cancer
Authors: Christopher A. Lang, David F. Ransohoff
Journal: JAMA (1994)

Annual fecal occult blood test (FOBT) screening using rehydrated Hemoccult slides has been reported in the Minnesota Colon Cancer Control Study to reduce colorectal cancer mortality by about 33%. However, some of the benefit of FOBT screening may come from "chance" selection of persons for colonoscopic examination because of the high positivity rate of FOBT (about 10%) that may occur for reasons other than a bleeding cancer or polyp. To determine how much this mechanism could account for the benefit of FOBT screening, we used a simple mathematical model to simulate the course of a cohort of screened persons, incorporating published data including those from the Minnesota study. The results suggest that one third to one half of the mortality reduction observed from FOBT screening in the Minnesota study may be attributable to chance selection for colonoscopy. We conclude that annual FOBT screening with rehydration is a haphazard method for selecting persons for colonoscopy. (<i>JAMA</i>. 1994;271:1011-1013)
Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors
Authors: Jeffrey B. Wyckoff, Yarong Wang, Elaine Y. Lin, Jiu-feng Li, Sumanta Goswami, E. Richard Stanley, Jeffrey E. Segall, Jeffrey W. Pollard, John Condeelis
Journal: Cancer Research (2007)

Although the presence of macrophages in tumors has been correlated with poor prognosis, until now there was no direct observation of how macrophages are involved in hematogenous metastasis. In this study, we use multiphoton microscopy to show, for the first time, that tumor cell intravasation occurs in association with perivascular macrophages in mammary tumors. Furthermore, we show that perivascular macrophages of the mammary tumor are associated with tumor cell intravasation in the absence of local angiogenesis. These results show that the interaction between macrophages and tumor cells lying in close proximity defines a microenvironment that is directly involved in the intravasation of cancer cells in mammary tumors.
Severe drug‐induced anaphylaxis: analysis of 333 cases recorded by the<scp>A</scp>llergy<scp>V</scp>igilance<scp>N</scp>etwork from 2002 to 2010
Authors: J.‐M. Renaudin, E. Beaudouin, C. Ponvert, P. Demoly, D.‐A. Moneret‐Vautrin
Journal: Allergy (2013)

Abstract Background A few series of well‐documented cases of severe drug‐induced anaphylaxis ( SDA ) are available. Methods Cases collected by the A llergy V igilance N etwork from 2002 to 2010 were analyzed for clinical signs, causative drugs, and efficacy of a stepwise approach to diagnosis, using skin tests, laboratory tests, and oral challenges. Results Three hundred and thirty‐three cases concerned 300 adults (90.1%) and 33 children (9.9%): 206 females (61.9%) and 127 males (38.1%). Mean age was 42.7 ± 18 years. Anaphylactic shock (76.6%), severe systemic reactions (10.5%), acute laryngeal edema (9%), severe bronchospasm (2.1%), and six fatal cases (1.8%) were recorded. There were 270 cases (81.1%) of ambulatory anaphylaxis. Sixty‐three cases (18.9%) occurred during anesthesia. Hospitalization was required in 94.8% of cases. 23.7% of patients were admitted to an intensive care unit. Epinephrine was used in 57.9% of cases. Eighty‐four drugs were incriminated: antibiotics (49.6%), muscle relaxants, latex and anesthetics (15%), nonsteroidal anti‐inflammatory drugs (10.2%), acetaminophen (3.9%), iodinated or magnetic resonance imaging contrast media (4.2%), immunotherapy and vaccines (3.9%), and other drugs (13%). Among antibiotics, amoxicillin (97 cases), other penicillins (four cases), cephalosporins (41 cases), quinolones (15 cases), and pristinamycin (seven cases) were the most common. The diagnosis of drug hypersensitivity was obtained by skin tests in 72.9%, laboratory tests only in 2.4% of cases, and oral challenges (OCs) only in 3.9% of cases. Conclusions Three hundred and thirty‐three case reports provided data on drugs involved in severe anaphylaxis. The efficacy of skin tests and poor use of laboratory tests are underlined. Further progress may depend on OCs.
Irreversible bronchial goblet cell metaplasia in hamsters with elastase-induced panacinar emphysema.
Authors: T G Christensen, A L Korthy, G L Snider, J A Hayes
Journal: Journal of Clinical Investigation (1977)

A single intratracheal instillation of pancreatic elastase in hamsters induces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchial epithelium of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, produced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P less than 0.005) than that of unexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear but the possibility is raised that the bronchial changes may be due to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, under appropriate circumstances, a single pulmonary insult in man could lead to a permanent lung injury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.
Data for Peer Review: Acquisition and Use
Authors: RICHARD L. GOLDSTEIN
Journal: Annals of Internal Medicine (1975)

Nine Experimental Medical Care Review Organizations (EMCROs) review the process and outcome of medical care, using insurance billing claims or medical record abstracts as the data source. The cost of EMCRO insurance billing claims processing in 1972, including peer review, ranged from $0.47 to $2.50 per claim. Three EMCROs reviewed the necessity for elective hospital admission prospectively for $2.50, $8.50, and $10.02 per case. The EMCROs developed innovative methods for abstracting hospital, nursing home, and ambulatory medical records at a cost of $0.40 to $4.00 per abstract. These EMCRO cost estimates were not derived from uniform accounting methods. Problems of accuracy and comparability of data for peer review are discussed. The EMCRO experience may aid local implementation of Professional Standards Review Organizations (PSROs).
Glomerulonephritis associated with Coxiella burnetii endocarditis.
Authors: J R Dathan, M F Heyworth
Journal: BMJ (1975)

A patient with endocarditis associated with chronic Coxiella burnetii infection is described in whom glomerulonephritis developed with granular deposits containing immunoglobulins and complement in the glomeruli. The serum was notable for the variety of circulating antibodies detected, which included antibodies directed against native DNA.
The kindness of strangers
Authors: Francesca Towey
Journal: The Lancet Psychiatry (2014)

For most, June 14, 2008, was just a normal day. For Jonny Benjamin, it was the day he decided that he no longer wanted to live. A month earlier, Jonny had been diagnosed with schizoaffective disorder, but had discharged himself from the hospital where he was receiving treatment. As Jonny stood on the edge of Waterloo Bridge in London, contemplating suicide, a stranger took the time to stop, talk, and provided words of hope to prompt his recovery. The documentary Finding Mike, released in association with the charity Rethink Mental Illness, follows Jonny on his mission to find this stranger.
Discordance between serum cardiac biomarker and immunoglobulin‐free light‐chain response in patients with immunoglobulin light‐chain amyloidosis treated with immune modulatory drugs
Authors: Angela Dispenzieri, David Dingli, Shaji K. Kumar, S. Vincent Rajkumar, Martha Q. Lacy, Suzanne Hayman, Frances Buadi, Stephen Zeldenrust, Nelson Leung, Kristen Detweiler‐Short, John A. Lust, Stephen J. Russell, Robert A. Kyle, Morie A. Gertz
Journal: American Journal of Hematology (2010)

Abstract We evaluated the capability of soluble cardiac biomarkers to predict tolerability and outcomes of IMiD‐containing treatments among 106 patients treated on clinical trials. Baseline elevations in troponin T (TnT) and N‐terminal brain naturietic protein (NT‐proBNP) predicted for an inability to tolerate IMiD‐based regimens. The best predictors for early attrition during cycle 1 were TnT ≥ 0.07 μg/L and NT‐proBNP ≥ 11,939 ng/L. NT‐proBNP‐response underperformed TnT‐response as a predictor for overall survival (OS), but both predicted for early protocol attrition. Despite hematologic response, IMiD‐treated patients were at higher risk for NT‐proBNP rises and early drug discontinuation than a control population but not for early death. These observations prompt two questions: (1) does IMiD‐based therapy lead to increased fluid retention and/or cardiac toxicity and (2) is an NT‐proBNP‐driven cardiac response system valid in IMiD‐treated amyloidosis patients? Recognition of potential drug‐induced cardiac toxicity is important so that increased cardiac surveillance and drug dose‐adjustment or discontinuation may be implemented. Am. J. Hematol. 85:757‐759, 2010. © 2010 Wiley‐Liss, Inc.
Multiple apocrine cystadenomas
Authors: THOMAS V. KRUSE, MUSHTAQ A. KHAN, MEDHAT O. HASSAN
Journal: British Journal of Dermatology (1979)

A 56-year-old man had approximately forty apocrine cystadenomas 01 the face and ears. Clinical examination and light microscopic findings were typical for apocrine cystadenomas. Electron micro- scopic findings showed an absence of annulate lamellae, thus dififering from the only previously reported study. Review of the literature indicates that a large number of apocrine cystadenomas, such as on our patient, has not been reported previously.
High-level Malignant Obstruction of Common Hepatic Duct Treated by Permanent Intubation
Authors: R. R. Hunter, S. A. Zaheer
Journal: BMJ (1962)

Kent abdomen, N.A.D. Hb 90% (14 g./100 ml.).E.S.R. 22 mm.(Westergren).W.B.C. 9.700/c.mm. (N.86%.E. 0%, B. 1%, L. 13%).Liver-function tests: serum conjugated bilirubin 7 mg./100ml.; serum alkaline phosphatase 46 K.A. units; thymol turbidity I unit; zinc sulphate turbidity 8
Inhibition of α <sub>4</sub> Integrin and ICAM-1 Markedly Attenuate Macrophage Homing to Atherosclerotic Plaques in ApoE-Deficient Mice
Authors: Shilpesh S. Patel, Ram Thiagarajan, James T. Willerson, Edward T. H. Yeh
Journal: Circulation (1998)

Background —Monocytes/macrophages play a central role in many stages of development of atherosclerotic plaques, including the conversion to an unstable morphology with rupture and fissuring. A better understanding of the mechanism of attachment of monocytes to activated endothelial cells would prove useful in developing strategies aimed at blocking this initial step. Here we describe a novel in vivo model that directly demonstrates homing of macrophages to atherosclerotic plaques. Methods and Results —Macrophages were loaded with fluorescent microspheres and injected intravenously into 40-week-old apolipoprotein E–deficient mice. After 48 hours, labeled macrophages were observed adhering to all stages of atherosclerotic plaques from the early fatty streak to mature calcified lesion. The mean number of macrophages adherent to atherosclerotic plaques located in the proximal 1 mm of the aortic root was quantitated by counting serial frozen sections and found to be 143±17 macrophages per aortic root. Pretreatment of the apolipoprotein E–deficient mice with monoclonal antibodies directed against the α-subunit of the α 4 β 1 integrin and against intracellular cell adhesion molecule (ICAM-1) reduced macrophage homing by 75% and 65%, respectively, as compared with isotype-matched controls ( P &lt;.05). Pretreatment with a monoclonal antibody directed against E-selectin did not significantly reduce macrophage homing. Conclusions —These data demonstrate that α 4 integrin and ICAM-1 play major roles in the recruitment of macrophages to atherosclerotic plaques, whereas E-selectin does not appear to contribute significantly to macrophage recruitment. This model will be useful for studying the mechanism of macrophage recruitment to atherosclerotic plaques and for evaluating the efficacy of inhibitors to adhesion molecules in preventing macrophage recruitment.
Egr-1: is it always immediate and early?
Authors: Shi Fang Yan, David J. Pinsky, Nigel Mackman, David M. Stern
Journal: Journal of Clinical Investigation (2000)

The early growth response gene product (Egr-1) is a zinc finger transcription factor (1, 2) first identified because of its characteristic pattern of expression following exposure of cells to mediators associated with growth and differentiation.Egr-1 (also called Zif268, NGF1-A, Krox24, or TIS8) has been termed an immediate-early response protein, based on the brisk kinetics of its induction, within minutes of a stimulus, and
TUMOR INDUCTION BY IMMUNOLOGICALLY ACTIVATED MURINE LEUKEMIA VIRUS
Authors: Martine Y. K. Armstrong, Nancy H. Ruddle, Muriel B. Lipman, Frank F. Richards
Journal: The Journal of Experimental Medicine (1973)

A graft-vs.-host reaction (GVHR) was induced in young male CAFI and CB6F1 mice by the administration of BALB/cJ spleen cells. A proportion of such mice subsequently developed lymphoreticular rumors. Cell-free extracts (CFEs) prepared from the reticular tissues of CAF1 mice killed at intervals after the induction of the GVHR were tested for their capacity to produce the same tumors in a litter of syngeneic mice inoculated at birth. 12 of 29 (41.4%) such extracts were positive, causing lymphoreticular tumors in one or more littermate recipients. The positive CFEs came from donors killed at all stages of the GVHR, from tumor-bearing mice as well as from non-tumor-bearing mice. However, whereas less than 30% of CFEs from mice killed within 12 mo of GVHR induction were oncogenic, the incidence of oncogenic extracts from mice killed 12–15 mo after GVHR induction rose to 75%. None of the CFEs prepared from nine normal uninjected male CAF1 mice killed between the ages of 8 and 18 mo transmitted tumors to recipients. CFEs prepared from CAF1 mice with the GVHR were tested for infectious murine leukemia virus (MuLV) using the XC assay and also for complement-fixing (CF) group-specific MuLV antigen. Substantial titers of B-tropic MuLV and CF antigen were detected in at least half the extracts from mice killed 11–14 mo after GVHR induction. During the first few months of GVHR induction, MuLV titers were low and CF antigen was absent. Neither infectious MuLV nor CF antigen were detected in CFEs prepared from normal control mice. Serially passed CFEs originating from a CB6F1 GVHR-induced RCN caused similar tumors in successive generations of syngeneic recipient mice. These lymphoreticular tumors were shown to contain infectious MuLV, CF MuLV antigen, and C-type particles. These data together provide evidence that MuLV is activated during the GVHR and that it is responsible for the eventual development of lymphoreticular tumors.
Abstract 2117: Constitutively active androgen receptor variants upregulate expression of mesenchymal markers in prostate cancer cells
Authors: Félicie COTTARD, Irène ASMANE, Eva ERDMANN, Jean-Pierre BERGERAT, Jean-Emmanuel KURTZ, Jocelyn CERALINE
Journal: Cancer Research (2014)

Abstract Androgen receptor (AR) signaling pathway remains the main target of novel therapeutics for castration-resistant prostate cancer (CRPC). However, constitutively active AR variants lacking the carboxy-terminal region in CRPC lead to therapy inefficacy. Moreover, recent studies suggest that AR variants are expressed in primary prostate tumors and may contribute to tumor progression. The aim of this study was to investigate the impact of AR variants on tumor progression. N-cadherin expression was analyzed in LNCaP cells overexpressing the wild type AR or a constitutively active AR variant by qRT-PCR, Western blot and immunofluorescence. We showed here for the first time that N-cadherin expression was increased in the presence of constitutively active AR variants. Moreover, this increased expression of N-cadherin in LNCaP overexpressing AR variants was negatively regulated by androgens. Although N-cadherin expression is often associated with a downregulation of E-cadherin, this phenomenon was not observed in our model. Nevertheless, in addition to the increased expression of N-cadherin, an upregulation of other mesenchymal markers expression such as Vimentin, SNAIL and ZEB1 was observed in the presence of constitutively active AR variants. In conclusion, our findings highlight novel consequences of constitutively active AR variants on the regulation of mesenchymal markers in prostate cancer. Citation Format: Félicie COTTARD, Irène ASMANE, Eva ERDMANN, Jean-Pierre BERGERAT, Jean-Emmanuel KURTZ, Jocelyn CERALINE. Constitutively active androgen receptor variants upregulate expression of mesenchymal markers in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2117. doi:10.1158/1538-7445.AM2014-2117
Analgesia in terminal malignant disease.
Authors: C Drinkwater, R G Twycross
Journal: BMJ (1979)

ProblemLast year an inoperable rectal carcinoma on the posterior wall of her rectum was diagnosed in a 79-year-old widow.A colostomy was formed, which was followed up by cryosurgery and radio- therapy that produced symptomatic relief until ten weeks ago.For just over two months, however, the severe pain in her rectum has not responded to intrathecal hypertonic saline and the anaesthetists are unwilling to perform a caudal block.She is having Brompton cocktail, 10 ml regularly every four hours, supplemented by methadone as necessary, but she still has excruciating pain several times a day.What additional treatment would you suggest for her pain? AdviceI saw the patient this morning.Her rectal pain is caused by a malignant ulcer that is affecting the posterior part of her anus.The pain varies in intensity between background discomfort and agony, but it is helped by sitting on a cushion with a hole in the middle.She is having 10 ml of the British National Formulary "Brompton" cocktail (morphine, 1 mg/ml; chlorpromazine, 1-25 mg/ml; and cocaine, 1 mg/M) as well as metha- done, 10 mg, on an irregular basis-usually twice to thrice daily.There are four general approaches to the-control of pain: modification of pathological process, interruption of pain path- ways, raising the pain threshold, and modification of life style (including immobilisation).So far as modification of the patho.; logical process is concerned, there is little-that can be done.Her
Breadth of neutralization and synergy of clinically relevant human monoclonal antibodies against HCV genotypes 1a, 1b, 2a, 2b, 2c, and 3a
Authors: Thomas H.R. Carlsen, Jannie Pedersen, Jannick C. Prentoe, Erick Giang, Zhen-Yong Keck, Lotte S. Mikkelsen, Mansun Law, Steven K.H. Foung, Jens Bukh
Journal: Hepatology (2014)

Human monoclonal antibodies (HMAbs) with neutralizing capabilities constitute potential immune-based treatments or prophylaxis against hepatitis C virus (HCV). However, lack of cell culture-derived HCV (HCVcc) harboring authentic envelope proteins (E1/E2) has hindered neutralization investigations across genotypes, subtypes, and isolates. We investigated the breadth of neutralization of 10 HMAbs with therapeutic potential against a panel of 16 JFH1-based HCVcc-expressing patient-derived Core-NS2 from genotypes 1a (strains H77, TN, and DH6), 1b (J4, DH1, and DH5), 2a (J6, JFH1, and T9), 2b (J8, DH8, and DH10), 2c (S83), and 3a (S52, DBN, and DH11). Virus stocks used for in vitro neutralization analysis contained authentic E1/E2, with the exception of full-length JFH1 that acquired the N417S substitution in E2. The 50% inhibition concentration (IC50) for each HMAb against the HCVcc panel was determined by dose-response neutralization assays in Huh7.5 cells with antibody concentrations ranging from 0.0012 to 100 μg/mL. Interestingly, IC50 values against the different HCVcc's exhibited large variations among the HMAbs, and only three HMAbs (HC-1AM, HC84.24, and AR4A) neutralized all 16 HCVcc recombinants. Furthermore, the IC50 values for a given HMAb varied greatly with the HCVcc strain, which supports the use of a diverse virus panel. In cooperation analyses, HMAbs HC84.24, AR3A, and, especially HC84.26, demonstrated synergistic effects towards the majority of the HCVcc's when combined individually with AR4A. Conclusion : Through a neutralization analysis of 10 clinically relevant HMAbs against 16 JFH1-based Core-NS2 recombinants from genotypes 1a, 1b, 2a, 2b, 2c, and 3a, we identified at least three HMAbs with potent and broad neutralization potential. The neutralization synergism obtained when pooling the most potent HMAbs could have significant implications for developing novel strategies to treat and control HCV. (Hepatology 2014;60:1551–1562)