tbuckley/cabot-search huggingface dataset:
Assessment of Ventricular Function after Acute Myocardial Infarction by Plasma Volume Expansion
Authors: HENRY S. LOEB, SHAHBUDIN H. RAHIMTOOLA, KENNETH M. ROSEN, M. ZIAD SINNO, RUBEN CHUQUIMIA, ROLF M. GUNNAR
Journal: Circulation (1973)

In order to see if changes in preload could be used to help assess left ventricular function, 24 patients with uncomplicated acute myocardial infarction (AMI) received plasma volume expansion (PVE). In eight patients (group A) cardiac index (CI) increased by 20% or more, and in 16 patients (group B) CI increased by less than 20% or decreased. By plotting left ventricular stroke-work index (LVSWI) against left ventricular end-diastolic pressure (LVEDP) before and after PVE, the ventricular function curves upon which the heart was operating could be assessed. In group A patients the values moved upward and to the right, while in group B the values during PVE moved horizontally or downward and to the right suggesting that at rest these hearts were operating at the peak of their function curves. Patients in group B had a higher incidence of anterior infarction and a lower control mean arterial pressure than patients in group A, but other clinical and control hemodynamic values did not differ between the two groups. Follow-up data suggest that patients in group B may have had a higher mortality within the first 6 months following AMI. Changing preload by PVE appears to be a safe and potentially useful means of assessing ventricular function following AMI and deserves further study.
The Critical Question of Procedure Volume Minimums for Coronary Angioplasty
Authors: Thomas J. Ryan
Journal: JAMA (1995)

In this issue ofThe Journal, Kimmel and colleagues<sup>1</sup>present important evidence from the data registry of the Society for Cardiac Angiography and Interventions (SCA&amp;I) that the inverse relationship documented to exist between the number of percutaneous transluminal coronary angioplasty (PTCA) procedures performed at a hospital and the rate of major complications related to the procedure at that institution is independent of differences in patients' risk profile. Although it may seem intuitively clear that procedural volume should bear a meaningful relationship to patient outcome, the argument is made that any observed differences in outcomes between lower-volume and higher-volume laboratories and operators are likely due to the fact that those with lower procedural volumes more often deal with a higher-risk population comprising patients who are sicker, in need of more urgent care, and unsuitable for transfer to higher-volume centers. Although this argument has been refuted for a number of selected
A piece of my mind. Leek soup
Authors: J. F. Gardner
Journal: JAMA (1991)

Cecille first walked into my office dressed in blue stretch pants and a flowered blouse under a full-length camel's hair coat. Her graying, soft brown hair was cut Dutch-boy style. Everything about her suggested middle America except for a mink coif she wore regally. "I never expected to live this long," she said, after exchanging initial pleasantries. I was caught off-guard by her remark and laughed nervously for lack of any comeback. Her daughter, who had accompanied Cecille into the examination room, rolled her eyes as one does who has heard something countless times before. "Now, Mother. God's not ready for you yet," came the practiced reply. Cecille was born in 1900. She doesn't look a day over 65. Her slender records reveal only two medical problems: hypertension and hyperlipidemia. Her blood pressure is easily controlled with an ACE inhibitor, but her total cholesterol has never dipped below 300 mg/dL.
The Microsatellite Instable Subset of Colorectal Cancer Is a Particularly Good Candidate for Checkpoint Blockade Immunotherapy
Authors: Yanping Xiao, Gordon J. Freeman
Journal: Cancer Discovery (2015)

Abstract Summary: The microsatellite instable (MSI) subset of colorectal cancer exhibits an active Th1/CTL immune microenvironment, probably due to recognition of a high number of tumor neoantigens. However, the high expression of checkpoint molecules PD-1, PD-L1, CTLA-4, LAG-3, and IDO in MSI colorectal cancer distinguishes MSI from microsatellite stable colorectal cancer and creates an immunosuppressive microenvironment that may help MSI tumors evade immune destruction by the infiltrating immune cells. Though colorectal cancer does not have a good response rate to PD-1 pathway immunotherapy, these results suggest that the MSI subset of colorectal cancer is a particularly good candidate for checkpoint immunotherapy. Cancer Discov; 5(1); 16–8. ©2015 AACR. See related article by Llosa et al., p. 43
Organic Dust Toxic Syndrome: Animal House Fever?
Authors: Bruce B. Dan
Journal: JAMA (1987)

During an average lifetime, the lungs will expand and contract some 500 million times and will be exposed to billions of liters of inspired air—and everything that it contains. Not surprisingly, exposure to particulate matter can cause a multitude of pulmonary problems—the thousand natural shocks that flesh is air to. Most of these illnesses are the result of immunologic reactions to a variety of inhaled antigens including bacteria, fungi, protozoa, and plant or animal proteins. Excluding actual infections, most of these events have been grouped under the category referred to as<i>hypersensitivity pneumonitis</i>. Although hypersensitivity pneumonitis had been recognized as a potential consequence of an occupational exposure since the early 18th century, it was only 50 years ago that a direct relationship was demonstrated between the onset of a respiratory illness in farmers and their exposure to moldy hay.<sup>1</sup>Since then, that particular entity and other reactions from acute exposures
Severe Hypoglycemia and Smoking in a Long-Term Type 1 Diabetic Population
Authors: Flavio E. Hirai, Scot E. Moss, Barbara E.K. Klein, Ronald Klein
Journal: Diabetes Care (2007)

The purpose of this study was to evaluate the relationship of severe hypoglycemia and smoking in a population-based cohort of individuals with long-term type 1 diabetes.This was a cross-sectional analysis of the population-based cohort of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. The analyses in this report were limited to 537 type 1 diabetic individuals with complete data who participated in the last examination phase (2000-2001). Severe hypoglycemia was defined as having one or more episodes of loss of consciousness or overnight hospitalization attributable to hypoglycemia in a 1-year period before the examination.The prevalence of severe hypoglycemia in this population was 14.3%. In univariate analysis, current smokers had a greater chance of having severe hypoglycemia compared with never smokers (odds ratio 2.40 [95% CI 1.30-4.40]). When we controlled for relevant confounders such as age, sex, A1C, waist-to-hip ratio, orthostatic hypotension, alcohol consumption, intensive insulin treatment, past history of severe hypoglycemia, and late complications of diabetes (nephropathy, neuropathy, and retinopathy), the association remained statistically significant, with current smoking presenting approximately 2.6 times greater odds of developing severe hypoglycemia.Current smokers with type 1 diabetes have higher odds of severe hypoglycemia episodes.
Lifestyle Changes for Improving Disease-specific Quality of Life in Sedentary Men on Long-term Androgen-Deprivation Therapy for Advanced Prostate Cancer: A Randomised Controlled Trial
Authors: Liam Bourke, Stephen Gilbert, Richard Hooper, Liz A. Steed, Miland Joshi, Jim W.F. Catto, John M. Saxton, Derek J. Rosario
Journal: European Urology (2013)
Pancreatic Endosonography after Billroth II Gastrectomy
Authors: J. H. Lee, M. Topazian
Journal: Endoscopy (2004)

Background and Study Aims: Prior Billroth II gastrectomy is considered a relative contraindication to endoscopic ultrasonography (EUS) of the pancreatic head. This study reviews experience with pancreatic EUS in such patients. Patients and Methods: Eleven patients were identified who had previous Billroth II gastrectomy and underwent attempted pancreatic EUS. Results: Examination of the pancreatic head was technically feasible in 10 of the patients. The inferior pancreatic head, ampulla, and periampullary ducts were seen in all; the superior pancreatic head and porta hepatis were visualized in 50 % of cases with radial echo endoscopes and 100 % with a linear-array echo endoscope. The pancreatic neck was fully imaged in 25 % of cases with radial echo endoscopes and in 60 % with a linear-array echo endoscope. One known pancreatic neck mass was not visualized. Conclusions: Pancreatic EUS is technically feasible in most patients with a prior Billroth II gastrectomy. Linear-array echo endoscopes provide a more complete examination than radial echo endoscopes. The pancreatic neck may be difficult to visualize.
Are Rhinovirus-induced Airway Responses in Asthma Aggravated by Chronic Allergen Exposure?
Authors: Josephine de Kluijver, Christine E. Evertse, Jacob K. Sont, Jasmijn A. Schrumpf, Christel J. G. van Zeijl-van der Ham, Claire R. Dick, Klaus F. Rabe, Pieter S. Hiemstra, Peter J. Sterk
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Airway inflammation in asthma may represent a favorable environment for respiratory viral infections, augmenting virus-induced exacerbations in asthma. We postulated that repeated low-dose allergen exposure preceding experimental rhinovirus 16 (RV16) infection increases the severity of RV-induced airway obstruction and inflammation. Thirty-six house dust mite–allergic patients with mild to moderate asthma participated in a three-arm, parallel, placebo-controlled, double-blind study. Patients inhaled a low dose of house dust mite allergen for 10 subsequent working days (Days 1–5 and 8–12) and/or were subsequently infected with RV16 (Days 15 and 16). Allergen exposure resulted in a significant fall in FEV1 (p < 0.001) and provocative concentration of histamine causing a 20% fall in FEV1 (p < 0.001) and an increase in exhaled nitric oxide (p < 0.001) and percentage of sputum eosinophils (p < 0.001). RV16 infection led to a fall in FEV1 (p = 0.02) and increases in the percentage of sputum neutrophils (p = 0.01), sputum interleukin-8 (p = 0.04), and neutrophil elastase (p = 0.04). Successive allergen exposure and RV16 infection had no synergistic or additive effect on any of the clinical or inflammatory outcomes. In conclusion, repeated low-dose allergen exposure and RV16 infection induce distinct inflammatory profiles within the airways in asthma without apparent interaction between these two environmental triggers. This suggests that preceding allergen exposure, at the used dose and duration, is not a determinant of the severity of RV-induced exacerbations in patients with mild to moderate asthma.
259 ANTIVIRAL EFFICACY OF RIBAVIRIN MONOTHERAPY FOLLOWED BY STANDARD COMBINATION TREATMENT IN CHRONIC HEPATITIS C
Authors: B. Fülöp, U. Mihm, B. Schlosser, M. Biermer, A. Brodzinski, F. van Bömmel, P. Rhode, P. Buggisch, C. Sarrazin, T. Berg
Journal: Journal of Hepatology (2010)
Mutations in the integrin α7 gene cause congenital myopathy
Authors: Yukiko K. Hayashi, Fan-Li Chou, Eva Engvall, Megumu Ogawa, Chie Matsuda, Shinichi Hirabayashi, Kenji Yokochi, Barry L. Ziober, Randall H. Kramer, Stephen J. Kaufman, Eijiro Ozawa, Yu-ichi Goto, Ikuya Nonaka, Toshifumi Tsukahara, Jian-zhou Wang, Eric P. Hoffman, Kiichi Arahata
Journal: Nature Genetics (1998)
Abstract 3956: Hedgehog acyltransferase: A key player in Sonic hedgehog signalling in cancer cells
Authors: Biljana Jovanovic, Shu-Chun Chang, Mirella Koleva, Anthony I. Magee
Journal: Cancer Research (2010)

Abstract Protein acyltransferases (PATs), a group of enzymes that catalyze acylation of a variety of proteins, have recently been shown to play an important part in protein sorting and signalling in the cell. In the Sonic hedgehog (Shh) signalling pathway the PAT Hedgehog acyltransferase (Hhat) is responsible for addition of a palmitic acid (C16) to the N-terminal cysteine residue of Shh. In mice, this modification has been shown to be necessary for proper packaging and release of Shh from the signalling cell as well as for transmitting a potent signal to the receiving cell, rendering Hhat crucial for a functioning Shh signal. Aberrant regulation of the Shh signalling pathway leads to a variety of malignant diseases in adults. Oncogenic activation of the Shh signalling pathway is known to arise from excessive production of the Shh signal or oncogenic mutations in the signal receiving cell. To date, drug therapies targeting the pathway in cancer have been directed at Shh-independent mutations in downstream regulators, Ptch, Smo, and Su(Fu), in the signal-receiving cell. To complement this, we hypothesize that Hhat is a potential drug target in cancers dependent on excessive Shh production for their growth. Here, we validate the potential of Hhat as a therapeutic target in cancer cell lines dependent on Shh for their growth. By knocking down Hhat in established cancer cell lines using siRNA we show that proper distribution and signalling by Shh can be inhibited. We measure the effect of the knock-down on target gene expression of the pathway (Ptch and Gli1), cancer cell growth and invasive properties of the cells. The effect is validated against inhibition of the Shh pathway by the Shh blocking antibody 5E1, and KAAD-cyclopamine, a Smo antagonist. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3956.
Role of Mitochondrial Aldehyde Dehydrogenase in Nitroglycerin-Induced Vasodilation of Coronary and Systemic Vessels
Authors: Jian Zhang, Zhiqiang Chen, Frederick R. Cobb, Jonathan S. Stamler
Journal: Circulation (2004)

It has recently been shown that mitochondrial aldehyde dehydrogenase 2 (mtALDH) catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from nitroglycerin (glyceryl trinitrate [GTN]) within mitochondria, leading to production of cGMP and vasorelaxation. However, whether this mechanism operates in the systemic and coronary beds that subserve the antianginal action of GTN is not known. In this study, we address this question in an intact canine model.Fourteen healthy mongrel dogs (weight, 20 to 25 kg) were studied. Coronary blood flow and hemodynamics were continuously monitored by a pulse Doppler flow probe implanted around the left circumflex coronary artery and with catheters in left ventricle and aorta, respectively. Each dog was given a 1-mL bolus injection of GTN, sodium nitroprusside (SNP), or adenosine through a catheter in the left atrium before and 30 minutes after infusion of cyanamide (17 mg/kg), an inhibitor of mtALDH. Cyanamide significantly inhibited both the classic dehydrogenase and GTN reductase activities of mtALDH in situ and attenuated the coronary blood flow increase and declines in blood pressure and left ventricular end-diastolic pressure produced by GTN in vivo. In contrast, mtALDH inhibition had no effect on the coronary and systemic effects of SNP and adenosine.Our data suggest that mtALDH contributes to GTN biotransformation in vivo and thus at least partly underlies the antianginal mechanism of drug action. Our findings also highlight the differences in biometabolism of clinically relevant nitrosovasodilators.
Dipsticks for spontaneous bacterial peritonitis: Comments on a long-awaited study report
Authors: Anastasios Koulaouzidis, Elmuhtady Said, Anthia Gatopoulou, John Moschos
Journal: Hepatology (2007)

We read with interest the study by Nousbaum et al. on the use of leukocyte reagent esterase strips for the diagnosis of spontaneous bacterial peritonitis.1 It is by far the biggest and the only multicenter study of a total of 16 prospective studies conducted (all published as full papers). Since the reports by Vanbiervliet et al.2 and Castellote et al.3, almost all strips (UriScan, Multistix 8SG and 10SG, Aution, Combur, Nephur) have come under scrutiny in small, single-center or 2-center studies, which reported sensitivities between 50% and 100% and specificity ranging between 81% and 100%.4, 5 We would like to draw attention to a couple of points. First, the number of included patients is slightly different (n = 1041) than the number found (n = 1069) in abstract presentations of the same study 2 years ago. That seems to have raised the initially reported sensitivity of the Multistix 8SG from 43.6% to 45.3%.6, 7 Second, in the current abstract of the study, the authors report that 2 reactive strips were tested independently in patients undergoing paracenteses. It is clear that the investigators did not use different brands of dipsticks to check the total of 2123 ascitic fluid samples. We assume this statement means that every sample was double tested on the spot (with 2 Multistix 8SG). If that is the case, then we wonder if the 2 dipstick readers were each reading the dipstick they had each immersed in the sample, or was there eventually obligatory cross-reading. Operator subjectivity and interobserver variability is extremely important for dipstick tests, and we are not sure if the reported concordance (K = 0.805) between the readers refers to a total of 2123 or in fact 4246 readings. Anastasios Koulaouzidis M.D. MRCP*, Elmuhtady Said MBBS , Anthia Gatopoulou M.D., Ph.D. , John Moschos M.D., Ph.D. , * Llandudno General Hospital, North Wales, UK, Queen Elizabeth Hospital, Gateshead, UK, 424 Army Hospital, Thessalonika, Greece.
THE ETIOLOGY OF VERRUGA PERUANA
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1927)

A saline suspension of a subcutaneous nodule excised from a verruga patient, and kept in the refrigerator for 14 days, on inoculation into two young Macacus rhesus monkeys (Nos. 33 and 34) induced irregular febrile reactions and enlargement of the lymph glands, and in one instance a subcutaneous nodule arose, independently of direct inoculation, on the tail. A microorganism has been isolated from the blood of both animals, and from the experimental nodule, which in pathogenic properties and in cultural and morphological characteristics is indistinguishable from the strain of Bartonella bacilliformis isolated from a case of Oroya fever. The spontaneous skin lesion of Monkey 34 and the subcutaneous nodules induced by intradermal inoculation of cultures of the microorganism were histologically typical of experimental verruga lesions in monkeys and identical with the skin lesions induced in monkeys by Bartonella bacilliformis. The organism, like Bartonella bacilliformis, is an intracellular parasite, being found in the cytoplasm of the proliferating endothelial cells of the lesions and in the erythrocytes of the blood. The same variations in the manifestations of disease which have been noted in experimental infection with Bartmetta bacilliformis were observed in the experimental verruga infection. In the second passage (Monkey 41) the infection induced by local inoculation of cultures was severe both locally and constitutionally and was accompanied by marked anemia. The organisms were found in the red cells in large numbers. In the third passage the systemic infection was less severe, but the local lesions were more striking. Detection of the parasites in the blood is far more certain by the cultural method than by microscopic examination, the latter procedure being successful only in rather severe infections. The result of blood culture is therefore the decisive method in the final diagnosis of the disease. Preliminary serological study shows that the organism isolated in the present instance from the skin lesion of a verruga patient and that previously obtained from the blood of a case of Oroya fever belong to the same serological group. The data obtained justify the conclusion that verruga peruana is caused by Bartonella bacilliformis. They also definitely establish the fact that the inoculation of blood or sanguineous exudate from lesions of verruga peruana is capable of inducing in susceptible individuals a severe febrile systemic infection, such as that to which Carrion succumbed. The designation "Carrion's disease" is therefore the appropriate one for both forms of the infection. Bartonella bacilliformis may be regarded as a bacterium, since it has the essential features of that group of microorganisms.
Allergen immunotherapy: does it work and, if so, how and for how long?
Authors: D. Robinson
Journal: Thorax (2000)

Background.Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment.Methods.We conducted a randomised, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective.During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication.Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge.Cutaneous biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T cell infiltration and the presence of cytokine-producing T helper cells (Th2 cells) (as evidenced by the presence of interleukin-4 messenger RNA).A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease.Results.Scores for seasonal symptoms and the use of rescue antiallergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy and there was no significant difference between patients who continued immunotherapy and those who discontinued it.Symptom scores in both treatment groups (median areas under the curve in 1995, 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy, p=0.60) were markedly lower than those in the group that had not received immunotherapy (median value in 1995, 2863).Although there was a tendency for immediate hypersensitivity to allergen to return late after discontinuation, there was sustained reduction in the late skin response and associated CD3+ T cell infiltration and interleukin-4 messenger RNA expression.Conclusions.Immunotherapy for grass pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity.(N Engl J Med 1999;341:468-75) * Allergen injection immunotherapy (AII) is effective for grass pollen hay fever not responding to conventional medical therapy and can result in a 50% reduction in symptoms, an 80% reduction in treatment requirement, and improved quality of life scores.* The clinical response persists for at least three years after a three year course of grass pollen AII.* Allergen immunotherapy for hay fever should only be given by experienced hospital allergy clinics.* AII for other allergens may be effective but requires more research.* Further comparative research is needed to define the role of AII in asthma.* Further studies are needed on cost effectiveness.