tbuckley/cabot-search huggingface dataset:
Elotuzumab in Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma
Authors: Sagar Lonial, Ravi Vij, Jean-Luc Harousseau, Thierry Facon, Philippe Moreau, Amitabha Mazumder, Jonathan L. Kaufman, Xavier Leleu, L. Claire Tsao, Christopher Westland, Anil K. Singhal, Sundar Jagannath
Journal: Journal of Clinical Oncology (2012)

This phase I study evaluated elotuzumab, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (MM).Three cohorts were enrolled and treated with elotuzumab (5.0, 10, or 20 mg/kg intravenously) on days 1, 8, 15, and 22 of a 28-day cycle in the first two cycles, and days 1 and 15 of each subsequent cycle; lenalidomide 25 mg orally [PO] on days 1 to 21; and dexamethasone 40 mg PO weekly. Dose-limiting toxicities (DLTs) were assessed during cycle 1 of each cohort, and clinical responses were evaluated during each cycle. The first five patients received up to six cycles of therapy; subsequent patients were treated until disease progression.Twenty-nine patients with advanced MM and a median of three prior MM therapies were enrolled; 28 patients were treated, three each in the 5.0-mg/kg and 10-mg/kg cohorts and 22 in the 20-mg/kg cohort. No DLTs were observed up to the maximum proposed dose of 20 mg/kg. The most frequent grade 3 to 4 toxicities were neutropenia (36%) and thrombocytopenia (21%). Two patients experienced a serious infusion reaction (one grade 4 anaphylactic reaction and one grade 3 stridor) during the first treatment cycle. Objective responses were obtained in 82% (23 of 28) of treated patients. After a median of 16.4 months follow-up, the median time to progression was not reached for patients in the 20-mg/kg cohort who were treated until disease progression.The combination of elotuzumab, lenalidomide, and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM.
MicroRNAs Regulate Ocular Neovascularization
Authors: JiKui Shen, Xiaoru Yang, Bing Xie, Yangjian Chen, Mara Swaim, Sean F Hackett, Peter A Campochiaro
Journal: Molecular Therapy (2008)

In this study, we used ischemia-induced retinal neovascularization (NV) as a model to investigate the possible role of microRNAs in a clinically important disease process. Microarray analysis demonstrated seven microRNAs (miR-106a, -146, -181, -199a, -214, -424, and -451) that were substantially increased and three microRNAs (miR-31, -150, and -184) that were substantially decreased in ischemic retina. Potential targets for the upregulated microRNAs were not identified, but bioinformatic analysis suggested target genes for the downregulated microRNAs, and these were confirmed using a luciferase reporter assay. Real-time reverse transcriptase PCR confirmed that the substantial levels of miR-31, -150, and -184 present in normal retina were significantly reduced in ischemic retina. Interestingly, constitutive levels of miR-31 and -184 are high in the cornea and lens, two avascular tissues. Intraocular injection of pre-miR-31, -150, or -184 significantly reduced ischemia-induced retinal NV, and injection of pre-miR-31 or -150 also significantly reduced choroidal NV. These data suggest that alteration of microRNA levels contributes to two types of ocular NV, and that injection or enhanced expression of microRNAs is a potential therapeutic strategy.
Imaging Tumor Vascular Heterogeneity and Angiogenesis using Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Authors: Alan Jackson, James P.B. O'Connor, Geoff J.M. Parker, Gordon C. Jayson
Journal: Clinical Cancer Research (2007)

Abstract This article reviews the application of dynamic contrast-enhanced magnetic resonance imaging in both clinical studies and early-phase trials of angiogenesis inhibitors. Emphasis is placed on how variation in image acquisition and analysis affects the meaning and use of derived variables. We then review the potential for future developments, with particular reference to the application of dynamic contrast-enhanced magnetic resonance imaging to evaluate the heterogeneity of tumor tissues.
Alarm symptoms and identification of non-cancer diagnoses in primary care: cohort study
Authors: R. Jones, J. Charlton, R. Latinovic, M. C Gulliford
Journal: BMJ (2009)

<b>Objective</b> To evaluate the predictive value of alarm symptoms for specified non-cancer diagnoses and cancer diagnoses in primary care. <b>Design</b> Cohort study using the general practice research database. <b>Setting</b> 128 general practices in the UK contributing data, 1994-2000. <b>Participants</b> 762 325 patients aged 15 or older. <b>Main outcome measures</b> Up to 15 pre-specified, non-cancer diagnoses associated with four alarm symptoms (haematuria, haemoptysis, dysphagia, rectal bleeding) at 90 days and three years after the first recorded alarm symptom. For each outcome analyses were implemented separately in a time to event framework. Data were censored if patients died, left the practice, or reached the end of the study period. <b>Results</b> We analysed data on first episodes of haematuria (11 108), haemoptysis (4812), dysphagia (5999), or rectal bleeding (15 289). Non-cancer diagnoses were common in patients who presented with alarm symptoms. The proportion diagnosed with either cancer or non-cancer diagnoses generally increased with age. In patients presenting with haematuria, the proportions diagnosed with either cancer or non-cancer diagnoses within 90 days were 17.5% (95% confidence interval 16.4% to 18.6%) in women and 18.3% (17.4% to 19.3%) in men. For the other symptoms the proportions were 25.7% (23.8% to 27.8%) and 24% (22.5% to 25.6%) for haemoptysis, 17.2% (16% to 18.5%) and 22.6% (21% to 24.3%) for dysphagia, and 14.5% (13.7% to 15.3%) and 16.7% (15.8% to 17.5%) for rectal bleeding. <b>Conclusion</b> Clinically relevant diagnoses are made in a high proportion of patients presenting with alarm symptoms. For every four to seven patients evaluated for haematuria, haemoptysis, dysphagia, or rectal bleeding, relevant diagnoses will be identified in one patient within 90 days.
Book Review: Concise Oxford Textbook of Medicine
Authors: T J Ulahannan
Journal: Journal of the Royal Society of Medicine (2001)

What is the purpose of a concise textbook? Before embarking on such a work the editors should have a clear idea of the answer. The full version of the Oxford Textbook of Medicine, now the standard British reference work, comes in three sizeable volumes and is expensive. Professor Ledingham and Professor Warrell envisage their concise version appealing particularly to students and junior doctors.

In this sector of the marketplace there is much competition. Other short textbooks have established themselves in the hearts and minds of students and junior doctors with liberal use of coloured illustrations, useful lists in boxes and practical advice on common procedures. In these respects the Concise Oxford Textbook of Medicine is lacking. The editors seem to have interpreted their task literally, simply editing down the original and carrying over the eccentricities of the original. Thus diabetes, covered in a chapter of the section on metabolic diseases, is given the same weight in the organization of the book as inherited disorders of aminoacid metabolism. While this may be understandable in the encyclopaedic original, one expects a concise text to emphasize the topics of greatest importance while others are deleted or ruthlessly pruned.

For undergraduates considering a first textbook of medicine or graduates preparing for higher exams, a more focused text might be a wiser investment. However, for those who seek the essence of the full Oxford Textbook of Medicine without its bulk, the Concise Textbook represents a good buy.
Lack of Arginine Vasopressin–Induced Phosphorylation of Aquaporin-2 Mutant AQP2-R254L Explains Dominant Nephrogenic Diabetes Insipidus
Authors: Fabrizio de Mattia, Paul J.M. Savelkoul, Erik-Jan Kamsteeg, Irene B.M. Konings, Peter van der Sluijs, Rudolf Mallmann, Alexander Oksche, Peter M.T. Deen
Journal: Journal of the American Society of Nephrology (2005)

Water homeostasis in humans is regulated by vasopressin, which induces the translocation of homotetrameric aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells. For this process, phosphorylation of AQP2 at S256 by cAMP-dependent protein kinase A is thought to be essential. Mutations in the AQP2 gene cause recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. Here, a family in which dominant NDI was caused by an exchange of arginine 254 by leucine in the intracellular C terminus of AQP2 (AQP2-R254L), which destroys the protein kinase A consensus site, was identified. Expressed in oocytes, AQP2-R254L appeared to be a functional water channel but was impaired in its transport to the cell surface to the same degree as AQP2-S256A, which mimics nonphosphorylated AQP2. In polarized renal cells, AQP2-R254L was retained intracellularly and was distributed similarly as AQP2-S256A or wild-type AQP2 in unstimulated cells. Upon co-expression in MDCK cells, AQP2-R254L interacted with and retained wild-type AQP2 in intracellular vesicles. Furthermore, AQP2-R254L had a low basal phosphorylation level, which was not increased with forskolin, and mimicking constitutive phosphorylation in AQP2-R254L with the S256D mutation shifted its expression to the basolateral and apical membrane. These data indicate that dominant NDI in this family is due to a R254L mutation, resulting in the loss of arginine vasopressin–mediated phosphorylation of AQP2 at S256, and illustrates the in vivo importance of phosphorylation of AQP2 at S256 for the first time.
Relationship between serum vitamin D levels and lower airway malacia in children undergoing fiberoptic bronchoscopy
Authors: Deborah Snijders, Calgaro Serena, Silvia Quartesan, Ilaria Bertozzi, Ivana Kozuh, Francesca Lunardi, Angelo Barbato
Journal: European Respiratory Journal (2013)

Studies in patients with asthma, cystic fibrosis (CF) and recurrent lower airway respiratory infections demonstrated vitamin D deficiency.  Little is known about vitamin D levels and its correlation with lower airway malacia in children.  Relationships between serum vitamin D, clinical characteristics, fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) findings were investigated in children with chronic lower airway diseases (CLADs).  METHODS:  We retrospectively analyzed 101 children (mean age, 85,4 months) who underwent FOB and BAL for CLADs from January 2011 until January 2013. Serum vitamin D was measured in 50 children with recurrent lower airway infection, 30 with laringo/bronchospasm and 21 with chronic cough. Relationships between vitamin D and age, month of evaluation, laboratory findings, FOB and BAL were evaluated.  RESULTS  The analysis performed in 101 pediatric patients (41 female) revealed 31 normal vitamin D level (>75 nmol/l ), 34 insufficiency (50-75 nmol/l), 36 deficiency (  Vitamin D levels were correlated with the month of evaluation with higher levels during summer months. Vitamin D insufficiency/deficiency was correlated with female gender [p=0,01, odds ratio 3,2 (CI 1.2 to 8.5)]; low vitamin D levels (  No difference were found between BMI, age, indication for FOB and presence of atopia or asthma  CONCLUSIONS:  In children with CLADs we found a relationship between lower vitamin D levels and female gender and presence of lower airway malacia.
Outcome of Out-of-Hospital Cardiac Arrest in New York City
Authors: Gary Lombardi
Journal: JAMA (1994)

To determine survival from out-of-hospital cardiac arrest in New York City and to compare this with other urban, suburban, and rural areas.Observational cohort study.New York City.Consecutive out-of-hospital cardiac arrests occurring between October 1, 1990, and April 1, 1991.Trained paramedics performed immediate postarrest interviews with care providers, using a standardized questionnaire.Entry criteria, elapsed time intervals, and nodal events conformed to Utstein recommendations. The single target end point was death or discharge home.Of 3243 consecutive cardiac arrests on which resuscitation was attempted, 2329 (72%) met entry criteria as primary cardiac events. Overall survival was 1.4% (99% confidence interval [CI], 0.9% to 2.3%). No patients were lost to follow-up. Survival from witnessed ventricular fibrillation was 5.3% (99% CI, 2.9% to 8.8%). Using survival from witnessed ventricular fibrillation for intersystem comparison, our survival rate was similar to that of Chicago, Ill (4.0%; 99% CI, 1.9% to 7.5%; P = .41), the only other large city on which data were available. However, it was significantly lower than that reported from midsized urban/suburban areas (33.0%; 99% CI, 30.4% to 35.6%; P < .0001) and suburban/rural areas (12.6%; 99% CI, 8.9% to 16.3%; P < .0001). Survival rate among arrests occurring after arrival of emergency medical services personnel (8.5%; 99% CI, 4.7% to 14.0%) was comparable with Chicago (6.6%; 99% CI, 3.3% to 11.5%; P = .41) but markedly lower than King County, Washington (36%; 99% CI, 28.6% to 43.8%; P < .0001).Survival from out-of-hospital cardiac arrest in New York City was poor. This was partly attributable to lengthy elapsed time intervals at every step in the chain of survival. However, examination of survival among arrests occurring after emergency medical services arrival suggests that other features may predispose residents of large cities to higher cardiac arrest mortality than individuals living in more suburban or rural settings. Since half the US population resides in large metropolitan areas, this represents a public health problem of considerable magnitude.
CCL22 Recruits CD4-positive CD25-positive Regulatory T Cells into Malignant Pleural Effusion
Authors: Xue-Jun Qin, Huan-Zhong Shi, Jing-Min Deng, Qiu-Li Liang, Jing Jiang, Zhi-Jian Ye
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The aim of this study was to explore the presence of the chemokines CCL22 and CCL17 in malignant pleural effusion, and the chemoattractant activity of these chemokines on CD4-positive CD25-positive Foxp3-positive regulatory T cells infiltrating into the pleural space. Experimental Design: The concentrations of CCL22 and CCL17 in both pleural effusions and sera from 33 patients with lung cancer were determined. Flow cytometry was done to determine T lymphocyte subsets in cell pellets of pleural effusion. Pleural cells were analyzed for the expression of CCL22 and CCL17. The chemoattractant activity of CCL22 for regulatory T cells in vitro and in vivo was also observed. Results: The concentration of CCL22 in malignant pleural effusion was significantly higher than that in the corresponding serum. Pleural fluid from lung cancer patients was chemotactic for regulatory T cells, and this activity was partly blocked by an anti-CCL22, but not by an anti-CCL17 antibody. Intrapleural administration of CCL22 of patients produced a marked progressive influx of regulatory T cells into pleural space. Conclusions: Compared with serum, CCL22 seemed to be increased in malignant pleural effusion, and could directly induce regulatory T cell infiltration into the pleural space in patients with malignant effusion.
Health Insurance Exchanges — Making the Markets Work
Authors: Richard G. Frank, Richard J. Zeckhauser
Journal: New England Journal of Medicine (2009)

Americans purchase health insurance in various ways. Some buy individual policies. For them, medical underwriting is common, and preexisting conditions can preclude, limit, or dramatically increase the cost of coverage. Many buy insurance through small employers, which typically offer little or no choice of plan. Their premiums tend to be higher than those of consumers purchasing through large employers, which can bargain effectively on prices. Large employers usually offer a modest selection of high-quality plans at competitive prices. Medicare recipients can join traditional Medicare and then choose drug coverage from any of dozens of stand-alone prescription-drug plans (PDPs) or join . . .
Linking hypoxia and iron homeostasis: a ‘plate’ full of factors
Authors: V Nathan Subramaniam, Daniel F Wallace
Journal: Gut (2014)

A case of Candida tropicalis endophthalmitis following penetrating keratoplasty is presented. The donor was an alcoholic, who died of bronchopneumonia and pancreatitis. We presume the candida infection was transmitted by the donor because Candida tropicalis was cultured in life from the donor9s throat swab and corresponding fungal elements were discovered post mortem in kidney sections of the donor.
Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism.
Authors: G E Rice, J M Munro, M P Bevilacqua
Journal: The Journal of Experimental Medicine (1990)

Inducible cell adhesion molecule 110 (INCAM-110) is a 110-kD glycoprotein expressed on cytokine-activated human vascular endothelial cells. mAb blocking studies indicate that INCAM-110 and intercellular adhesion molecule 1 (ICAM-1) independently support the adhesion of lymphocytes to activated human umbilical vein endothelial cell monolayers. Anti-CD11a/CD18 antibodies with anti-INCAM-110 mAb E1/6 produce greater inhibition of lymphocyte adhesion than either reagent alone, suggesting that INCAM-110 and LFA-1 are not an obligate receptor-ligand pair. Blood monocytes, but not polymorphonuclear leukocytes, also appear to bind endothelial INCAM-110. Endothelial expression of INCAM-110 is upregulated at sites of inflammation, suggesting a role in the recruitment of mononuclear leukocytes.
1061 HIGH CHOLESTEROL DIETS EXACERBATE MOUSE LIVER FIBROSIS THROUGH BUILDUP OF FREE CHOLESTEROL IN HEPATIC STELLATE CELLS
Authors: K. Tomita, T. Teratani, T. Suzuki, T. Oshikawa, H. Yokoyama, H. Ebinuma, H. Saito, R. Hokari, S. Miura, T. Hibi
Journal: Journal of Hepatology (2011)
Tetracycline for Seal Finger
Authors: Ed Sargent
Journal: JAMA (1980)

<h3>To the Editor.—</h3> Seal finger is to some people a common disease; however, as the following case illustrates, knowledge of this entity is widely lacking in the general medical community. Recognition of this potentially serious problem should be more widespread. <h3>Report of a Case.—</h3> A 27-year-old male graduate student stabbed his left palm with a knife while performing a necropsy on a sea lion, two days before being seen as an outpatient. At that time (April 4, 1979), erythema of 3 cm diameter around the 0.4-cm puncture wound was seen. After consultation, therapy with dicloxacillin, 500 mg four times a day, and hot soaks was instituted. Five days later there was some slight increased tenderness around the wound. Two days later there was increased swelling, erythema, and pain. Consultation with another specialist yielded a recommendation for treatment with cephalexin monohydrate, 1 g by mouth four times a day with discontinuation of
Is "nonusual interstitial pneumonia" an acceptable diagnosis?
Authors: J. Behr
Journal: European Respiratory Journal (2002)

The recently published “Classification of Idiopathic Interstitial Pneumonias (IIPs)” differentiates seven disease entities 1 as follows: 1) usual interstitial pneuminia (UIP), 2) desquamative interstitial pneumonia (DIP), 3) respiratory bronchiolitis-associated interstitial lung disease (RBILD), 4) nonspecific interstitial pneumonia (NSIP), 5) acute interstitial pneumonia (AIP), 6) cryptogenic organising pneumonia (COP), and 7) lymphoid interstitial pneumonia (LIP). These entities have primarily been defined pathologically 1. However, in clinical practice only a minority of patients with suspected IIP undergo surgical lung biopsy 3. Diagnostic criteria that allow a clinical diagnosis in the absence of a surgical lung biopsy have been defined only for UIP 4. In two previous publications the overall accuracy of a clinical diagnosis of UIP varied from 62–77% and the overall accuracy of a radiological diagnosis of UIP was about 75% 5. The most important noninvasive diagnostic tool for the diagnosis and differentiation of IIPs is the high-resolution computed tomography (HRCT) 7. …
Long-Term Efficacy of Metformin Therapy in Nonobese Individuals With Type 2 Diabetes
Authors: Cynthia R. Ong, Lynda M. Molyneaux, Maria I. Constantino, Stephen M. Twigg, Dennis K. Yue
Journal: Diabetes Care (2006)

The U.K. Prospective Diabetes Study (UKPDS) has demonstrated that metformin is as effective as sulfonylureas in obese subjects and is associated with less weight gain, fewer hypoglycemic episodes, and better cardiovascular outcomes. It is hence the pharmacological therapy of choice in this subgroup. However, a gap in our present knowledge is the long-term response to metformin in nonobese individuals. In this study, we compared metformin therapy in normal, overweight, and obese individuals with type 2 diabetes.A database of patients treated at a referral center in Sydney, Australia, were analyzed. Patients with type 2 diabetes and complete HbA(1c) (A1C) data and treated with metformin or sulfonylurea monotherapy for at least three visits before receiving dual oral therapy were included (n = 644). Analysis by BMI and the type of oral agent was performed. Individuals were categorized as normal, overweight, or obese (BMI <25, 25-29.9, and >/=30 kg/m(2), respectively).There were no differences between the initial, follow-up, and last A1C between the three metformin-treated groups. The duration of successful glycemic control with metformin monotherapy in the normal and overweight individuals and their incidences of diabetes-related complications for the entire duration of follow-up were not inferior to those of the obese individuals. The nonobese patients performed better regardless of the type of oral hypoglycemic agent used.We conclude that metformin is at least as efficacious in normal and overweight individuals as it is in those who are obese. Our study provides evidence-based data to support metformin use in nonobese individuals with type 2 diabetes.
Defective responsiveness to ascorbic acid of neutrophil random and chemotactic migration in Felty's syndrome and systemic lupus erythematosus.
Authors: E J Goetzl
Journal: Annals of the Rheumatic Diseases (1976)

A 72 year old man with simultaneously occurring squamous cell and neuroendocrine carcinomas in association with cryptogenic fibrosing alveolitis is reported. The tumours were separate and both were in the fibrotic area of the right lower lobe.
The E2F3-Oncomir-1 Axis Is Activated in Wilms' Tumor
Authors: Eric J. Kort, Leslie Farber, Maria Tretiakova, David Petillo, Kyle A. Furge, Ximing J. Yang, Albert Cornelius, Bin T. Teh
Journal: Cancer Research (2008)

Abstract Oncomir-1 is an oncogenic cluster of microRNAs (miRNA) located on chromosome 13. Previous in vitro studies showed that it is transcriptionally regulated by the transcription factor E2F3. In this report, we combine expression profiling of both mRNA and miRNAs in Wilms' tumor (WT) samples to provide the first evidence that the E2F3-Oncomir-1 axis, previously identified in cell culture, is deregulated in primary human tumors. Analysis of RNA expression signatures showed that an E2F3 gene signature was activated in all WT samples analyzed, in contrast to other kidney tumors. This finding was validated by immunohistochemistry on the protein level. Expression of E2F3 was lowest in early-stage tumors and highest in metastatic tissue. Expression profiling of miRNAs in WT showed that expression of each measured member of the Oncomir-1 family was highest in WT relative to other kidney tumor subtypes. Quantitative PCR confirmed that these miRNAs were overexpressed in WT relative to normal kidney tissue. These results suggest that the E2F3-Oncomir-1 axis is activated in WT. Our study also shows the utility of integrated genomics combining gene signature analysis with miRNA expression profiling to identify protein-miRNA interactions that are perturbed in disease states. [Cancer Res 2008;68(11):4034–8]