tbuckley/cabot-search huggingface dataset:
Does Drug Therapy Slow Radiographic Deterioration in Rheumatoid Arthritis?
Authors: Lisa Iannuzzi, Neal Dawson, Nazih Zein, Irving Kushner
Journal: New England Journal of Medicine (1983)

Many clinicians believe that slow-acting therapeutic agents, such as gold, penicillamine, the antimalarials, and cytotoxic drugs, can retard joint destruction in rheumatoid arthritis. We reviewed 60 published studies employing these drugs to evaluate critically the evidence that drug therapy can slow the radiographic progression of disease. Seventeen studies were found that included radiographic assessment of both treated and control groups; they were analyzed using methodologic criteria known to be important in affecting the results of drug trials. In addition to numerous qualitative methodologic deficiencies, many studies showed inadequacies in sample size and duration of treatment, and the drug dosage used varied from one study to another. We found evidence suggesting that both gold and cyclophosphamide can retard radiographic progression of joint destruction. At present, there are too few technically adequate studies to permit even provisional conclusions concerning other agents. (N Engl J Med 1983; 309:1023–8.)
The impact of polypharmacy on toxicity from chemotherapy in elderly patients: Focus on cytochrome P-450 inhibition and protein binding effects
Authors: M. Popa, K. Wallace, A. Brunello, M. Extermann
Journal: Journal of Clinical Oncology (2008)

9505 Background: Drug-drug and disease-drug interactions are significant clinical issues in the elderly. Of the elderly taking 3+ chronic medications, 33% are rehospitalized within 6 months of discharge from a hospital. Drug interactions can also be relevant to toxicity from chemotherapy, such as ketoconazole and irinotecan, via p450 inhibition, or oxaliplatin and warfarin, possibly via competition for protein binding. Methods: To assess the impact of polymedication on toxicity from chemotherapy, we analyzed a cohort of 290 patients 70+ receiving chemotherapy at Moffitt Cancer Center. In previous analyses using unweighted inhibition/induction of p450 interactions we found results approaching significance, and albumin level predicting non-hematologic toxicity. We refined our analysis by using weighted effects according to the strength of p450 inhibition/induction. We also assessed the impact of competition by highly protein-bound drugs (>50%). Stepwise logistic regression was used to assess predictors of G4 hematologic (G4H) or G3–4 non-hematologic (G3–4NH) toxicity. CART software was used to assess heterogeneity of effects. Results: In unconstrained models, higher likelihood of G4H was predicted by high competitive protein binding (p= 0.003), bone marrow invasion (p= 0.027), tumor stage (p=0.005), mean bilirubin (p= 0.025), and mean red blood cells during chemotherapy (p= 0.012). In unconstrained models, higher likelihood of G3–4H was predicted by higher BMI (p=0.048), tumor stage (p=0.029), lower mean albumin during chemotherapy (p=0.005), and higher AST before chemotherapy initiation (p=0.018). When entry order was preset with MAX2, p450 interaction, and competitive protein binding being entered first, MAX2 score (p=0.016) and competitive protein binding (p=0.009) predicted higher likelihood of G4H, but no predictor significantly influenced G3–4NH. The CART analyses indicate a dominant effect of MAX2 for G4H, and of mean albumin for G3–4NH, with no major heterogeneity. Conclusions: Our results suggest that drug distribution factors play important roles in chemotherapy toxicity in elders. The role of protein binding in the pharmacokinetics/dynamics of chemotherapy drugs should be further explored. No significant financial relationships to disclose.
Case 42-1967
Authors: Paul A. Kantrowitz, James M. Gibson
Journal: New England Journal of Medicine (1967)

Presentation of Case First admission. A forty-one-year-old woman entered the hospital because of swelling of the abdomen.After a hysterectomy five years earlier she had been informed that she had liver disease. Thereafter, her intake of alcohol, described as moderate previously, increased considerably, and she ate only one meal a day. One year before admission there was the onset of progressive swelling of the abdomen. Two months and again three weeks before admission she vomited a large quantity of blood. On admission to another hospital a week after the second episode the hemoglobin was 3.8 gm per 100 ml. . . .
An Integrated Procedure for the Rapid Diagnosis of Biliary Obstruction, Portal Hypertension and Liver Disease of Uncertain Etiology
Authors: P. Robert Strack, Howard K. Newman, Arthur G. Lerner, Stephen H. Green, Chien-Hsing Meng, Louis R. M. Del Guercio, David State
Journal: New England Journal of Medicine (1971)

Abstract An integrated procedure consisting of transhepatic cholangiography, liver biopsy and omentoportography, performed under local anesthesia through a 5-cm subxiphoid incision, was used in 100 patients with hepatobiliary disorders that presented major diagnostic or therapeutic problems. Cholangiography was successful in 80 of 91 patients, liver biopsy in all of 54 patients, and omentoportography in 13 of 15 patients. Diagnosis was achieved in all cases. The frequency of two of the three major complications that occurred should be reducible by sulture ligation of puncture sites. There were no deaths attributable to the procedure. Coagulation abnormalities were present in 29 patients. The only recognized contraindication is sensitivity to contrast medium. The integrated procedure is an effective method of resolving puzzling cases of hepatobiliary disease and should save much time and expense. It has also been helpful in the planning and execution of surgery for biliary obstruction and portal hypertension.
Relation of the Course of HIV Infection in Children to the Severity of the Disease in Their Mothers at Delivery
Authors: Stephane Blanche, Marie-Jeanne Mayaux, Christine Rouzioux, Jean-Paul Teglas, Ghislaine Firtion, Fabrice Monpoux, Nicole Cicaru-Vigneron, Francoise Meier, Joelle Tricoire, Christian Courpotin, Etienne Vilmer, Claude Griscelli, Jean-Francois Delfraissy
Journal: New England Journal of Medicine (1994)

Among infants with maternally transmitted human immunodeficiency virus (HIV) infection, there are two patterns of disease progression. In about a fifth of these infants there is a rapid progression to profound immunodeficiency, whereas in the majority the disease progresses much more slowly.
Reciprocal Relation between Renin Dependency and Sodium Dependency in Essential Hypertension
Authors: Haralambos Gavras, Artur B. Ribeiro, Irene Gavras, Hans R. Brunner
Journal: New England Journal of Medicine (1976)

To investigate the roles of angiotensin II and sodium in essential high-renin, normal-renin and low-renin hypertension, 14 patients received the competitive antagonist of angiotensin II, saralasin, during periods of sodium depletion and repletion. Blood-pressure response to saralasin was determined by the state of sodium balance. Patients from all three renin subgroups exhibited a fall in blood pressure when sufficiently sodium depleted, and an elevation in blood pressure when sodium replete or insufficiently depleted. However, those with low renin required loss of substantially more sodium (sufficient to elicit compensatory stimulation of renin) before depletion could be achieved. In patients with essential hypertension of all three renin subgroups, sodium balance determines the degree of participation of the renin-angiotensin system in sustaining high blood pressure. Even the low-renin type can become renin dependent with sufficient sodium depletion. (N Engl J Med 295:1278–1283, 1976)
Higher Bioelectric Potentials Due to Decreased Chloride Absorption in the Sweat Glands of Patients with Cystic Fibrosis
Authors: Paul M. Quinton, Jan Bijman
Journal: New England Journal of Medicine (1983)

Patients with cystic fibrosis have characteristic disturbances in the electrolyte composition of their sweat, saliva, and pancreatic secretions. We studied the electrical properties of sweat glands in eight patients with cystic fibrosis and in seven normal volunteers to determine the basis of the well-documented inhibition of sodium absorption in this disease. The average electrical potential across 47 sweat glands in the patients was -66.3 +/- 2.1 mV, as compared with -29.8 +/- 3.2 mV for 39 glands in the normal controls (P less than 0.001). The average sweat-secretion rate in 33 glands from six patients was not significantly different from that in 34 glands from six controls, but average concentrations of sodium, chloride, and potassium were significantly higher in sweat droplets from the patients. Calculated rates of both sodium and chloride reabsorption were lower in sweat glands of patients than of normal controls, but chloride reabsorption was more markedly reduced than sodium reabsorption. We conclude that a decrease in epithelial permeability to chloride may explain the characteristic changes in sweat electrolytes in cystic fibrosis and could be a generalized abnormality in the disease.
S120 Serum MicroRNA profiles in IPF patients – biomarkers or potential therapeutic targets?
Authors: P Minnis, R Kane, R Lumsden, S Whitty, SC Donnelly, MP Keane
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Idiopathic Pulmonary Fibrosis (IPF) has limited therapeutic options and predicting the natural history in individual cases is difficult. Exosomes are extracellular microvesicles that are involved in cell-cell signalling. MicroRNA isolated from exosomes has been implicated in several fibrotic models.<sup>1</sup> At present the role of miRNAs in development of lung fibrosis is unclear. We aim to characterise miRNAs isolated from IPF patients and relate these to measures of disease severity. <h3>Methods</h3> We assessed exosomes isolated from the serum of IPF patients (n = 8) and aged matched healthy controls (n = 6). Exosomes were characterised by western blot and Nanosight technology. MiRNA was isolated from these exosomes and profiled using a miRNA PCR assay. Demographic and clinical data was extracted from clinical records. IPF patients were stratified by radiological severity, GAP scoring and rate of progression. <h3>Results</h3> Exosomes isolated from IPF patients demonstrated decreased fold regulation in antifibrotic miRNA such as miR-141 and miR-29 in addition to increases in fibrogenic miRNA such as miR-7 when compared to healthy controls. The degree of up regulation in miR-7 correlates significantly with stratified burden of disease. Interestingly down regulation of miR-155 was also found which has been previously associated with up regulation in mice fibrosis models. Patients had a median follow up of 31 months (IQR 17–43). There was a significant correlation with regards to up regulation of miR-125b with milder disease defined by the GAP score and preservation of FVC. <h3>Conclusion</h3> This data identifies novel biomarkers that may provide insights into the natural history and pathogenesis of the disease. Furthermore miR-7 and miR-29 have been implicated in extracellular matrix remodelling with target genes including ECM proteins such as collagens, fibrillins and elastin. Inhibiting up regulated miRNA or supplementing down regulated miRNA may be potential therapeutic targets. <h3>Reference</h3> 1 Jiang X, Tsitsiou E, Herrick SE, <i>et al</i>. MicroRNAs and the regulation of fibrosis. <i>FEBS J</i>. 2010;<b>277</b>:2015–2021
Extramedullary Hematopoiesis: Breathtaking and Hair-Raising
Authors: Frans H. Krouwels, Paul Bresser, Albert E.G.K. von dem Borne
Journal: New England Journal of Medicine (1999)

To the Editor: The study by Tyson et al. (June 24 issue), 1 while impressive in design and numbers of infants studied, does not really answer the question of whether vitamin A supplementation reduces the risk of chronic lung disease in premature infants.The main drawback of this study, as well as those published previously, 2 is the definition of chronic lung disease.The best predictor of chronic lung disease is a chest x-ray film, 3 whereas the authors' definition of chronic lung disease, the need for oxygen at 36 weeks' postmenstrual age, has a positive predictive value of only 63 percent. 4lthough the authors found that fewer infants given vitamin A had chronic lung disease at 36 weeks (by their definition) than was the case in the control group, we question whether the difference is enough to convince a clinician to give 12 intramuscular injections to extremely-lowbirth-weight infants, especially when all other measures of chronic lung disease in this study were not different in the two groups.Their argument in favor of vitamin A supplementation would be greatly strengthened by additional follow-up data.
P45 Practical use of the DECAF score: Can we improve outcomes in acute exacerbation of COPD admissions?
Authors: L Collier, T David, C Craig, R Yadavilli
Journal: Thorax (2015)

<h3>Background</h3> Acute exacerbations of COPD (AECOPD) are the second most common cause of emergency hospital admission in England and are associated with an inpatient mortality rate of 4.3%.<sup>1</sup> The Dyspnoea, Eosinopenia, Consolidation, Acidaemia and Atrial Fibrillation (DECAF) Score, is an effective prognostic tool that predict mortality in AECOPD admissions. This scoring system is easy to apply during admission and has performed better than existing prognostic tools.<sup>2</sup> We aim to appraise the efficacy of DECAF score in our busy respiratory and medical admissions unit. <h3>Method</h3> Hospital admissions with AECOPD from Dec 2014 to Mar 2015 are prospectively reviewed and DECAF score applied to each patient. Morbidity and mortality indicators were then correlated with both total DECAF scores and each predictive index. <h3>Results</h3> 78 admissions were reviewed, 60% were male and the mean age was 72.7 years. Average length of stay was 15.3 days and 12 patients died in hospital. Our results were comparable with previous studies<sup>3</sup>, with inpatient mortality highest in those with DECAF scores of 3–5 (92%) and lowest in those with scores of 0–1 (0%). Higher DECAF scores were also associated with use of non-invasive ventilation (43%). Furthermore, each individual predictive index within the DECAF score was independently related to an increased mortality rate. There was 44% mortality in patients with atrial fibrillation and 30% mortality in patients with dyspnoea score of eMRC 5B. In-hospital mortality rate increased with each DECAF score (Figure 1). <h3>Conclusions</h3> Introduction of DECAF score as clinical prediction tool for AECOPD admissions in our departments may be beneficial in reducing morbidity and mortality. Those scoring highest should be considered for early escalation, higher level of care and or palliative management. Those with lower scores may be suitable for early supported discharge. Further study of a larger group however is advisable to confirm the significance of these findings. <h3>References</h3> 1 National Chronic Obstructive Pulmonary Disease Audit Programme: Clinical audit of COPD exacerbations admitted to acute units in England and Wales, 2014 2 J Steer, J Gibson, S Bourke. The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease.<i> Thorax</i> 2012;<b>67</b>:970–976
Brain Stem Gliomas
Authors: Gary Magram, Luis Schut
Journal: Neuro-Oncology (1991)

Brain stem gliomas are a heterogenous group of tumors. MRI scanning is the neurodiagnostic test of choice in defining the anatomy of these lesions. By combining the clinical exam with the neuro-imaging studies it is now possible to individualize patient management (Table 1). This paper reviews the criteria presently available to guide patient selection with regard to surgical intervention, radiation therapy, chemotherapy or conservative observation.
The Role of a Common Variant of the Cholesteryl Ester Transfer Protein Gene in the Progression of Coronary Atherosclerosis
Authors: Jan Albert Kuivenhoven, J. Wouter Jukema, Aeilko H. Zwinderman, Peter de Knijff, Ruth McPherson, Albert V.G. Bruschke, Kong I. Lie, John J.P. Kastelein
Journal: New England Journal of Medicine (1998)

The high-density lipoprotein (HDL) cholesterol concentration is inversely related to the risk of coronary artery disease. The cholesteryl ester transfer protein (CETP) has a central role in the metabolism of this lipoprotein and may therefore alter the susceptibility to atherosclerosis.
Underuse of Coronary Revascularization Procedures in Patients Considered Appropriate Candidates for Revascularization
Authors: Harry Hemingway, Angela M. Crook, Gene Feder, Shrilla Banerjee, J. Rex Dawson, Patrick Magee, Sue Philpott, Julie Sanders, Alan Wood, Adam D. Timmis
Journal: New England Journal of Medicine (2001)

Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances.This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography.Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction--the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93)--and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend=0.002).On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes.
Case 39-1998
Authors: John F. Dashe, Philip J. Boyer
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 13-year-old right-handed girl was admitted to the hospital because of a relapsing–remitting neurologic disorder.She had had a normal childhood, although she was awkward at running, bicycle riding, and gymnastics. Twenty-six months before admission, she had an acute febrile episode with otitis, pharyngitis, headache, drowsiness, imbalance, and confusion. A magnetic resonance imaging (MRI) examination of the brain showed signal abnormalities in both occipital lobes. A computed tomographic (CT) scan of the brain revealed radiolucent areas in both occipital lobes. The following month, the girl had a grand mal seizure, followed by cortical blindness for 18 hours, . . .
Treatment of Percistent Blepharitis and Keratoconjuctivitis with Intraocular and Topical Use of Tacrolimus 0.03% Ointment
Authors: Konstantinos Syrigos, Nikolaos K. Syrigos, Maria Vasiliou, Maria Zande, Ekaterini I. Syrigou
Journal: Journal of Allergy and Clinical Immunology (2016)
A retrospective review of demographics and stage of triple-negative breast cancer
Authors: F. N. Rana
Journal: Journal of Clinical Oncology (2009)

e11553 Background: Triple negative breast cancer (TNBC) is a recently recognized subtype of breast cancer, notable to metastasize early. It accounts for 15–20% of all breast cancers, and is more prevalent in African-American and Hispanic women, and women younger than 40 years of age. Continual decline in breast cancer deaths since 1990 has been attributed to earlier detection, better treatment including hormonal blockade in estrogen- and progesterone-receptor positive cancers, as well as the addition of Trastuzumab, a monoclonal antibody directed against the Her2/neu receptors. These hormone receptors are not found in TNBC, and therefore the traditional targets for endocrine manipulation cannot be therapeutically exploited. While lower socioeconomic status and racial predisposition to this disease have been observed, there exists a paucity of research into other demographic risk factors. We reviewed data between January 2000 to December 2005 from our tumor registry with particular attention to age, race, family history, tobacco use, and stage of presentation, comparing this subset of patients (n=39) to other records (n=303). We included only those patients in whom the status of all three receptors were recorded. Results: Comparisons were made for TNBC vs non-TNBC patients respectively as follows: mean age (59.87± yrs vs 60.09±yrs). Analysis using χ2 test (χ2=0.855) and CMH test for Linear Trend analysis (p=0.47) showed no difference in percentages in association with the 5 stages or TNBC status and no linear trend respectively. Conclusions: This data suggests that at our institution, TNBC is less prevalent (12.87%) than estimates of 15- 20% published in other studies. There was no difference in age at diagnosis (p=0.92), with black patients more likely to have TNBC (p=0.004, OR=2.75). There was no significant association between smoking status and TNBC (p=0.43). There was no significant association between a family history of cancer and TNBC (p=0.8384). When accounting for samples size, TNBC was as prevalent as non TNBC at all stages of diagnosis. These results differ from other published data and may reflect differences in statistical analysis. No significant financial relationships to disclose.