tbuckley/cabot-search huggingface dataset:
The relationship between right duct lymph flow and extravascular lung water in dogs given alpha-naphthylthiourea.
Authors: M B Pine, P M Beach, T S Cottrell, M Scola, G M Turino
Journal: Journal of Clinical Investigation (1976)

The relationship between right duct lymph flow and extravascular lung water was studied in 3 normal dogs and 15 dogs with pulmonary edema induced by alpha-naphthylthiourea (ANTU). Right duct lymph was collected in a pouch created by ligating jugular, subclavian, and brachiocephalic veins. Extravascular lung water was measured in vivo by double indicator dilution and post-mortem by weighting lungs before and after drying. Cardiac output, pulmonary artery and pulmonary artery wedge pressures, and the concentration of protein and electrolytes in plasma and right duct lymph were determined. Eight lungs were examined by light and electron microscopy. There was a direct relationship between right duct lymph flow (RDLF in milliters per hour per gram dry lung) and extravascular lung water (Qwl in milliliters per gram dry lung) which was best described by the equation RDLF=0.75-0.26 Qwl+0.03 (Qwl).2 Dogs with severe ANTU-induced edema had extensive lung capillary endothelial destruction but only mild interstitial swelling and no visible damage to type I alveolar epithelial cells. Cardiac output, pulmonary artery and wedge pressures, and protein and electrolyte concentrations did not correlate with either extravascular water or right duct flow. Thus, in ANTU-induced pulmonary edema right duct lymph flow was directly related to extravascular lung water with the highest flows occurring with severe edema. The absence of a rapid increase in lymph flow with small increases in extravascular water may be due to early sequestration of fluid in the alveolar space. Hemodynamic changes did not account for changes in lung water or lymph flow. The pulmonary interstitial factors relating increased extravascular water to lymph drainage remain to be determined.
Locally Advanced Pancreatic Cancer
Authors: Brian E. Kadera, Dharma B. Sunjaya, William H. Isacoff, Luyi Li, O. Joe Hines, James S. Tomlinson, David W. Dawson, Matthew M. Rochefort, Graham W. Donald, Barbara M. Clerkin, Howard A. Reber, Timothy R. Donahue
Journal: JAMA Surgery (2013)

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized.OBJECTIVE To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. DESIGN, SETTING, AND PARTICIPANTSRetrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected.MAIN OUTCOMES AND MEASURES Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling.RESULTS All 49 patients were deemed initially unresectable owing to vascular involvement.After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%)underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection.Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%)had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response.The median overall survival (OS) was 40.1 months (range, 22.7-65.9months).A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P = .007)and HP treatment response (hazard ratio, 9.0; P = .009)were most significant.Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P = .05).Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P = .04)than LN-positive patients.The candidate prognostic biomarkers, SMAD4 protein loss (P = .01)in tumor cells and microRNA-21 expression in the stroma (P = .05),also correlated with OS.On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P = .004).CONCLUSIONS AND RELEVANCE Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS.After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.
Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo.
Authors: G Cirino, C Cicala, M Bucci, L Sorrentino, G Ambrosini, G DeDominicis, D C Altieri
Journal: Journal of Clinical Investigation (1997)

Coagulation proteases were tested in a rat model of acute inflammation. Subplantar injection of Factor Xa (10-30 microg) produced a time- and dose-dependent edema in the rat paw, and potentiated carrageenin-induced edema. In contrast, the homologous protease Factor IXa was ineffective. This inflammatory response was recapitulated by the Factor Xa sequence L83FTRKL88(G), which mediates ligand binding to effector cell protease receptor-1 (EPR-1), while a control scrambled peptide did not induce edema in vivo. Conversely, injection of the EPR-1-derived peptide S123PGKPGNQNSKNEPP137 (corresponding to the receptor binding site for Factor Xa) inhibited carrageenin-induced rat paw edema, while the adjacent EPR-1 sequence P136PKKRERERSSHCYP150 was without effect. EPR-1-Factor Xa-induced inflammation was characterized by fast onset and prominent perivascular accumulation of activated and degranulated mast cells, was inhibited by the histamine/serotonin antagonists cyproheptadine and methysergide, but was unaffected by the thrombin-specific inhibitor, Hirulog. These findings suggest that through its interaction with EPR-1, Factor Xa may function as a mediator of acute inflammation in vivo. This pathway may amplify both coagulation and inflammatory cascades, thus contributing to the pathogenesis of tissue injury in vivo.
Economic Note: Cost of illness studies
Authors: S. Byford
Journal: BMJ (2000)

Cost of illness studies are a type of economic study common in the medical literature, particularly in specialist clinical journals. The aim of a cost of illness study is to identify and measure all the costs of a particular disease, including the direct, indirect, and intangible dimensions. The output, expressed in monetary terms, is an estimate of the total burden of a particular disease to society.1 It is widely believed that estimating the total societal cost of an illness is a useful aid to policy decision making, and indeed organisations such as the World Bank and the World Health Organization commonly use such studies.2 However, cost of illness studies have been the cause of much debate among economists.1 3 4

Two methods of costing illness exist—the prevalence and incidence …
The effects of cholesterol uptake from high-density lipoprotein subfractions on biliary sterol secretion in rats with essential fatty-acid deficiency
Authors: Jacob Wanon, France Guertin, Sylvain Brunet, Edgard Delvin, Victor Gavino, Daniel Bouthillier, Denis Lairon, Wagner Yotov, Emile Levy
Journal: Hepatology (1998)

High-density lipoprotein (HDL) participates in the transfer of cholesterol to the liver, in which it is subsequently excreted into bile as bile acid and cholesterol. In this study, the effect of essential fatty-acid (EFA) deficiency on cholesterol contribution from HDL subfractions to bile was investigated. Rats that were rendered EFA-deficient over 4 weeks displayed changes in their plasma HDL subfractions and liver tissue fatty acids. Plasma linoleic (18:2n6), linolenic (18:3n3,) and arachidonic (20:4n6) acids decreased, whereas palmitoleic (16:1n7) and eicosatrienoic (20:3n9) acids increased. EFA deficiency was confirmed by an elevation of the 20:3(n-9)/20:4(n-6) index. To examine the hepatic handling of lipoprotein-derived cholesterol, HDL2 and HDL3 from donor rats were isolated, labeled with [14C]-cholesterol, and injected iv into EFA-deficient and normal rats with a bile fistula. In HDL subfractions from control rats, no significant variations were noted in the specific activity of cholesterol output in both groups of EFA recipient rats; however, the output of biliary bile acids was significantly decreased in EFA-deficient rats following the administration of labeled HDL3. In HDL2 and HDL3 originating from EFA-deficient rats, a decrease in the specific activity of both biliary cholesterol and bile acid output was recorded in EFA-deficient rats. Concomitant with the defective HDL2- and HDL3-[14C] cholesterol translocation into bile of EFA-deficient rats, increased hepatic very-low-density lipoprotein (VLDL)-[14C] cholesterol secretion was observed in vivo. HDL2 and HDL3 particles, derived from EFA-deficient rats, had an altered composition including a depletion in apo A-I and an enrichment in apo E isoforms, which are the the two major HDL apolipoproteins involved in the delivery of cholesterol to the liver. Taken together, these results show that normal EFA status is necessary for efficient HDL-cholesterol processing by the liver.
The Continuing Search: FDA Drug Information Survey
Authors: Robert H. Moser
Journal: JAMA (1974)

On May 8, 1974, the Food and Drug Administration (FDA) Bureau of Drugs published the final report of "Survey of Drug Information Needs and Problems Associated With Communications Directed to Practicing Physicians." It is a fascinating document. It would seem that the FDA has accepted (assumed?) a broader mandate than many of us anticipated in its capacity as a regulatory agency. The report states: The Food and Drug Administration's Bureau of Drugs is responsible for a wide range of activities designed to insure that prescription drugs are<i>safely prescribed and used</i>, and appropriately advertised. The scope of these activities include FDA consideration of drug efficacy, quality, safety and labeling [italics added]. The breadth of implication in this statement lends itself to speculation about how the FDA might go about ensuring "safe prescription and use." But the thrust of this document indicates that the FDA is concerned with<i>educating physicians about</i>
Emphysema in COPD: consequences and causes
Authors: G M Turino
Journal: Thorax (2006)

There is still much to be learned about the cellular and cytokine reactions of specific phenotypes in COPD

The current definition of chronic obstructive pulmonary disease (COPD), which has been established by the Global Initiative on Obstructive Lung Disease (GOLD)1 and also adopted, in large part, by the American Thoracic Society and the European Respiratory Society,2 is that COPD is a “preventable and treatable disease state characterized by airflow limitation that is not fully reversible”. This definition has the virtue of simplicity and clinical applicability but necessarily includes patients with widely varying clinical phenotypes and pathogenic mechanisms. The paper by Boschetto et al 3 in this issue of Thorax focuses on the role of radiologically identified pulmonary emphysema in a group of patients diagnosed with COPD on the basis of their presenting clinical state and separated into groups for comparison between those with and without radiologically identified emphysema.

Patient selection began with 50 individuals with COPD who then underwent computed tomographic (CT) scanning with a third generation continuous-rotation scanner. The quantitation of emphysema is well described and the quality of the CT scan obtained is considered adequate to rule out the presence of significant emphysema,3 which is essential for the premises of the study. Importantly, the smoking history between the two patient groups was not significantly different, which suggests varying host factors as causes for the differences observed. The characterisation of patients includes the BODE index, which includes body mass, air flow obstruction, dyspnoea severity, and exercise measured by the 6 minute walk …
Abstract 5149: Intermedin stimulates cell growth, migration, and angiogenesis in human colorectal adenocarcinoma and hepatocellular carcinoma
Authors: Xiaojia Guo, John Schmitz, Edward Uchio, Barton Kenney, Sanjay Kulkarni, Charles Cha
Journal: Cancer Research (2011)

Abstract Intermedin (IMD) functions as an angiogenic factor in a rat ischemic model and human endothelial cells. In our search for anti-angiogenic therapy for solid tumors, we analyzed the expression and possible role of IMD in tumor angiogenesis. IMD was expressed in human colorectal adenocarcinoma (CRC) and hepatocellular carcinoma (HCC). The IMD expression was significantly higher in stage I than stage 0 of both colon and liver tumors (stage I/0 ratio of mRNA level is 7.7 ± 0.4 and 3.2 ± 0.3, respectively). IMD was widely expressed in colon and liver tumor lines. Immunohistochemistry showed that the tumor regions were significantly more immunoreactive for IMD than adjacent benign regions of CRC and HCC specimens. Inhibition of IMD expression by RNA interference reduced cell proliferation by 29.7 ± 6.7% (n = 3, p = 0.047) and impaired cell invasion by 27.8 ± 3.6% (n = 3, p = 0.016) in a HCC cell line SK-Hep-1. Addition of IMD peptide for 5 minutes to serum starved SK-Hep-1 cells increased the phosphorylation level of p44 and p42 MAP Kinase (Erk1/2), suggesting that IMD regulates Sk-Hep-1 cell growth, at least partly, through activating Erk1/2 signaling pathway. Similarly, IMD knockdown in a CRC cell line HCT116 reduced cell growth by 35.0 ± 1.4 % (n = 3, p = 0.018). Conditioned medium from IMD siRNA-transfected SK-Hep-1 cells reduced endothelial cell tube formation by 31.6 ± 6.8%. Conversely, over-expression of IMD in CRC RKO cells increased cell growth and induced cell migration significantly. Furthermore, treatment with RKO/IMD conditioned medium increased endothelial cell tube formation by 14. 7 ± 0.8% (n=4, p = 0.049). Thus, IMD stimulated HCC and CRC cell growth, migration, and invasion, indicating a role for IMD in tumor angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5149. doi:10.1158/1538-7445.AM2011-5149
Studies on the lipid composition of human small bowel mucosa.
Authors: D R Saunders, P O Ways, C M Parmentier, C E Rubin
Journal: Journal of Clinical Investigation (1966)

Until recent times there have been no techniques enabling the gastrointestinal physiologist to in- vestigate in vivo the intracellular phase of fat ab- sorption in man.With a hydraulic biopsy tube (2), the sequence of morphological changes in the small bowel absorptive cell was described after giving fatty meals to normal subjects (3, 4).However, there has been no thorough study of the composition of the lipids of human small bowel mucosa in the fasting state or during ab- sorption.In the present study, multiple mucosal biopsies were obtained with a hydraulic biopsy tube (2) from the distal duodenum in man.Their lipid composition was determined by micro- analytical techniques.A larger group of nor- mal subjects and a smaller group of patients with idiopathic hyperlipemia were studied.The in- fluence of certain dietary manipulations on in- testinal absorptive cell lipids was also investigated. MethodsNormal subjects.The 16 males and one female, aged 21 to 43 years, had no history suggestive of small bowel
THE EFFECT OF BACTERIAL ENDOTOXIN ON THE NEWBORN GUINEA PIG
Authors: Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1962)

Newborn guinea pigs (less than 24 hours old) are highly susceptible to the lethal effect of endotoxin and susceptibility decreases with age. The vulnerability to endotoxin has not been attributed to hypofunction of either the adrenal gland or the reticuloendothelial system of the newborn, since prior injection of corticosteroids provides only partial protection to endotoxin and newborn guinea pigs can efficiently remove colloidal substances from the circulation. In contrast to adults, newborns do not develop a delayed inflammatory reaction following intradermal injection of endotoxin, and after intravenous challenge frequently fail to display neutropenia and sustained fever.
Unusual Scintigraphic Appearance of Osteomyelitis Secondary to Atypical Mycobacterium
Authors: DOUGLAS J. KIMMEL, WILLIAM C. KLINGENSMITH
Journal: Clinical Nuclear Medicine (1980)

A Tc-99m-methylene diphosphonate study in a 41- year-old man demonstrated multiple regions of intense activity in the appendicular and axial skeleton, characteristic of metastatic disease. However, bone biopsy demonstrated atypical mycobacterium osteomyelitis; there was no evidence of neoplasm.
IL-10 Attenuates Excessive Inflammation in Chronic<i>Pseudomonas</i>Infection in Mice
Authors: JAMES F. CHMIEL, MICHAEL W. KONSTAN, JEANNE E. KNESEBECK, JAY B. HILLIARD, TRACEY L. BONFIELD, DEBORAH V. DAWSON, MELVIN BERGER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Cystic fibrosis (CF) lung disease is characterized by an excessive inflammatory response associated with chronic Pseudomonas aeruginosa endobronchial infection. Compared with bronchoalveolar lavage fluid from healthy subjects, lavage fluid from patients with CF contains elevated proinflammatory cytokines but negligible amounts of the anti-inflammatory cytokine interleukin-10 (IL-10). We sought to determine whether IL-10 deficiency results in increased local and systemic morbidity in mice with chronic endobronchial infection with P. aeruginosa embedded in agar beads and to determine if exogenous IL-10 might reduce these effects. Infected IL-10 knockout mice had more severe weight loss (p = 0.04) and increased area of lung inflammation (28 ± 4 versus 10 ± 2%, p < 0.002) but no alterations in bacterial burden compared with wild-type mice. Infected CD-1 mice treated with IL-10 had improved survival (p = 0.035), less severe weight loss (p < 0.005), fewer bronchoalveolar lavage neutrophils (3 × 105/ml versus 5 × 106/ml, p < 0.02), and decreased area of lung inflammation (11 ± 2 versus 35 ± 7%, p < 0.01) but no alterations in bacterial burden compared with placebo-treated mice. These data suggest that IL-10 is an important regulator of the inflammatory response to P. aeruginosa endobronchial infection and that further investigation into the use of IL-10 in CF is warranted. Chmiel JF, Konstan MW, Knesebeck JE, Hilliard JB, Bonfield TL, Dawson DV, Berger M. IL-10 attenuates excessive inflammation in chronic Pseudomonas infection in mice.
Urinary Porphyrin Excretion in Children is Associated with Exposure to Organochlorine Compounds
Authors: Jordi Sunyer, Mar Alvarez-Pedrerol, Jordi To-Figueras, Núria Ribas-Fitó, Joan O. Grimalt, Carmen Herrero
Journal: Environmental Health Perspectives (2008)

Hexachlorobenzene (HCB) and other organochlorines induce porphyria cutanea tarda (PCT) in animal studies. Evidence in humans, however, is contradictory. In neonates and adults from a population historically highly exposed to HCB (Flix, Catalonia, Spain), no relation with PCT or with porphyrin excretion was found.We aimed to analyze the association between urinary porphyrin excretion and exposure to HCB and other organochlorinated compounds in children 4 years of age.Our birth cohort included all newborns from Flix and the five surrounding towns (where no airborne pollution occurred). Among the 68 children with porphyrins we measured in cord blood, 52 children 4 years of age provided blood to measure organochlorine compounds, hair for methylmercury, and urine for porphyrin excretion pattern.Quantitative porphyrin excretion was within the normal values. However, total porphyrins, coproporphyrin I (CPI), and coproporphyrin III (CPIII) adjusted to creatinine excretion increased with increasing levels of HCB, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT), and polychlorinated biphenyl congener 153 (PCB-153). We found no association with methylmercury. When we fitted multiple pollutant models, p,p'-DDE had the strongest association. We found these associations in children from both Flix and other towns, and they were independent of breast-feeding and of organochlorine and porphyrin levels at birth.HCB at current levels did not induce porphyria or increase uroporphyrins. However, the increase of urinary coproporphyrins suggests an incipient toxic effect of the organochlorines, especially for p,p'-DDE, on the hepatic heme-synthesis pathway that differs from the major effects seen in PCT.
Coronary Bypass Surgery
Authors: Donald M. Fowell
Journal: JAMA (1982)

To the Editor.—  I am prompted to comment on the answers to the letter submitted by MD, Michigan concerning potential coronary surgery for the 55-year-old man with a 95% lesion in his left anterior descending (LAD) coronary artery (1982;247: 2828).  I believe that there are some pitfalls in the generalization contained in the response from the internist, Dr Jones, and would rather strongly support the views expressed by the cardiac surgeon, Dr Lawrie.  As a generalization, one would not dispute the statement that an isolated lesion in a single vessel does not usually merit coronary bypass surgery. However, I would feel differently about a 95% lesion in the middle third of the right coronary artery as compared with such a lesion in the LAD coronary artery, particularly if it were proximal to or just distal to the first perforator, as stated by Dr Lawrie. Mortality statistics in this situation do
Amphetamine abuse. Pattern and effects of high doses taken intravenously
Authors: J. C. Kramer
Journal: JAMA (1967)

Abuse of amphetamines administered intravenously has become a well established and extensive form of drug abuse. The abuse potential of these drugs when taken by the intravenous route is greater than when taken orally and is comparable to that of heroin or cocaine. Tolerance builds rapidly and an abstinence syndrome develops which leads to a typical pattern in which the user takes the drug continuously and in immense doses for about five days during which he does not sleep. During this time he gradually becomes more paranoid and disorganized. He then desists for a day or two and falls into a prolonged semicomatose state. Upon awakening he is still lethargic and feels the need to resume his drug for a new round.