tbuckley/cabot-search huggingface dataset:
EXPERIMENTS ON THE PRODUCTION OF SPECIFIC ANTISERA FOR INFECTIONS OF UNKNOWN CAUSE
Authors: Peyton Rous, George W. Wilson, Jean Oliver
Journal: The Journal of Experimental Medicine (1920)

There is present in serum of high precipitin titer, produced by the repeated injection of rabbits with the blood-free serum of guinea pigs or dogs, a principle highly toxic for animals of the species furnishing the antigen. Intravenously the serum causes severe shock, and even sudden death, while locally it gives rise to acute inflammatory changes and profuse capillary hemorrhages. The complete removal of hemolysins and hemagglutinins from the serum by exposing it repeatedly to washed red cells lessens its toxicity to only a slight degree and one obviously dependent on these elements; while the further removal of precipitin by specific precipitation in vitro has no detoxifying effect whatever. Whether the toxic principle is a hitherto unrecognized antibody or perhaps a toxic product of the interaction of precipitin and precipitinogen,—one formed as readily in the test-tube as in the animal body,—remains to be determined. The symptoms of guinea pigs and dogs given an intravenous injection of treated or untreated serum markedly resemble those of anaphylaxis, but our attempts at desensitization have been unsuccessful. The local lesion in guinea pigs is more severe than that of the Arthus phenomenon. But these differences from anaphylaxis may, of course, be dependent merely on differing proportions of constituents that are themselves, as yet, scarcely apprehended. Our observations, as here summed up, were made with a practical point in mind, and as regards this point they are of a discouraging nature. In papers already published it has been shown that sera specifically effective against infections of which the excitant is unknown can in some cases be obtained by using infected tissue itself as antigen. Such sera must, of course, be deprived of antibodies injurious to tissue, prior to their employment in the animal body; and this was successfully accomplished in our early experiments by exhaustion with washed red cells. The purpose of the present work was to determine whether serum used as antigen gives rise to injurious principles in the antiserum. For the serum of infected individuals would in many diseases form a convenient antigen. It is evident that injurious principles result from its use, and that they are not removed from the antiserum when the latter is exhausted with red cells and its precipitin removed by specific precipitation, nor can their action be nullified by desensitization as carried out in anaphylaxis. Unless the obstacle of their presence is in some way overcome the body fluids of infected human beings cannot be practically utilized for the production of antiserum. In test animals the difficulty is not so grave. For we have found that the toxic antiserum produces no enduring lesions when it is administered intravenously in non-lethal doses.
NSAIDs are linked to increased risk of venous thromboembolism, study finds
Authors: J. Wise
Journal: BMJ (2014)

A meta-analysis has found a statistically significant increased risk of deep vein thrombosis and pulmonary embolism in users of non-steroidal anti-inflammatory drugs (NSAIDs), which has led researchers to say that these drugs should be prescribed with caution.

NSAIDs are among the most commonly used classes of drugs, but they are well known for their potential adverse effects. For example, in 2004 rofecoxib (Vioxx) was withdrawn from the market because of concerns about an increased risk of myocardial infarction and sudden …
Diagnostic value of a rapid test for B‐type natriuretic peptide in patients presenting with acute dyspnoe: effect of age and gender
Authors: Cathrine Wold Knudsen, Jon Sigurd Riis, Alexandra V. Finsen, Lars Eikvar, Carl Müller, Arne Westheim, Torbjørn Omland
Journal: European Journal of Heart Failure (2003)
Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest
Authors: Maxwell Simon Damian, Diana Ellenberg, Ramona Gildemeister, Jörg Lauermann, Gregor Simonis, Wolfgang Sauter, Christian Georgi
Journal: Circulation (2004)

Therapeutic hypothermia can improve survival after cardiopulmonary resuscitation (CPR). Coenzyme Q10 (CoQ10) has shown a protective effect in neurodegenerative disorders. We investigated whether combining mild hypothermia with CoQ10 after out-of-hospital cardiac arrest provides additional benefit.Forty-nine patients were randomly assigned to either hypothermia plus CoQ10 or hypothermia plus placebo after CPR. Hypothermia with a core temperature of 35 degrees C was instituted for 24 hours. Liquid CoQ10 250 mg followed by 150 mg TID for 5 days or placebo was administered through nasogastric tube. Age, sex, premorbidity, cause of arrest, conditions of CPR, and degree of hypoxia were similar in both groups; no side effects of CoQ10 were identified. Three-month survival in the CoQ10 group was 68% (17 of 25) and 29% (7 of 24) in the placebo group (P=0.0413). Nine CoQ10 patients versus 5 placebo patients survived with a Glasgow Outcome Scale of 4 or 5. Mean serum S100 protein 24 hours after CPR was significantly lower in the CoQ10 group (0.47 versus 3.5 ng/mL).Combining CoQ10 with mild hypothermia immediately after CPR appears to improve survival and may improve neurological outcome in survivors.
Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis
Authors: G. Michael, L. Xiao, X.-Y. Qi, D. Dobrev, S. Nattel
Journal: Cardiovascular Research (2008)

Cardiac action potentials (APs) are driven by ionic currents flowing through specific channels and exchangers across cardiomyocyte membranes. Once initiated by rapid Na+ entry during phase 0, the AP time course is determined by the balance between inward depolarizing currents, carried mainly by Na+ and Ca2+, and outward repolarizing currents carried mainly by K+. K+ currents play a major role in repolarization. The loss of a K+ current can impair repolarization, but there is a redundancy of K+ currents so that when one K+ current is dysfunctional, other K+ currents increase to compensate, a phenomenon called 'repolarization reserve'. Repolarization reserve protects repolarization under conditions that increase inward current or reduce outward current, threatening the balance that governs AP duration. This protection comes at the expense of reduced repolarization reserve, potentially resulting in unexpectedly large AP prolongation and arrhythmogenesis, when an additional repolarization-suppressing intervention is superimposed. The critical role of appropriate repolarization is such that cardiac rhythm stability can be impaired with either abnormally slow or excessively rapid repolarization. In cardiac disease states such as heart failure and atrial fibrillation (AF), changes in ion channel properties appear as part of an adaptive response to maintain function in the face of disease-related stress on the cardiovascular system. However, if the stress is maintained the adaptive ion channel changes may themselves lead to dysfunction, in particular cardiac arrhythmias. The present article reviews ionic remodelling of cardiac repolarization, and focuses on how potentially adaptive repolarization changes with congestive heart failure and AF can have arrhythmogenic consequences.
ABC of major trauma. Management of limb injuries.
Authors: K M Willett, H Dorrell, P Kelly
Journal: BMJ (1990)

WUb s 41(1) Reduction of a major deformity; (a) perform gentle longitudinal traction) (b) restore the correct rotation; (c) restore the alignment.(2) Control of the fracture; check pulses (x); maintain traction; apply a splint.Up to 70% of multiply injured patients have injured limbs and fractures or dislocations of the appendicular skeleton.Severe limb injurie-s must not distract the resuscitation team from the priorities of establishing an airway, optimising ventilation, and restoring circulatory volume as limb injuries are rarely immediately life threatening, except those that cause exsanguination.Careful thorough examination, however, is required after resuscitation to identify injuries, particularly those threatening the survival of limbs or fractures whose acute management will influence overall mortality or morbidity.Apparently minor injuries must likewise not be neglected as these may result in long term disability or disfigurement.* Traumatic amputation * Major vascular injury *
120. Stimulation of the Synthesis of Type-II Collagen and Extracellular Matrix in Human Normal and Osteoarthritic Articular Cartilage Explants In Situ by Overexpression of Human sox9 by rAAV-Mediated Gene Transfer
Authors: Henning Madry, Tanja Thurn, Dieter Kohn, Ernest F. Terwilliger, Magali Cucchiarini
Journal: Molecular Therapy (2005)

Top of pageAbstract
The transfer of therapeutic genes may have potential value in enhancing the reparative activities of human articular cartilage. We tested the hypothesis that overexpression of sox9 via rAAV leads to the production of a transcription factor capable of influencing the tissue architecture and cell phenotype in normal human and osteoarthritic articular cartilage explants in situ. A human sox9 cDNA tagged by a FLAG sequence was cloned in rAAV (rAAV-FLAG-hsox9). Explants from normal human (tumor surgery) and osteoarthritic articular cartilage (total knee arthroplasty; Mankin score 7-9) were transduced by rAAV-FLAG-hsox9 or rAAV-lacZ and processed after 10 days to monitor transgene expression, for histological and morphometric analyses (safranin O, hematoxylin eosin, type-II collagen), and to measure the proteoglycan, type-II collagen, and DNA contents. Morphometric measurements were performed along the explant surface (AnalySIS and Scion Image programs). Safranin O staining intensity is the ratio positively stained surface to the total surface examined. Type-II collagen staining intensity is in pixels per standardized area. Dose-dependent transgene expression (b-gal, FLAG, sox9) was seen in the explants. Treatment by rAAV-FLAG-hsox9 did not modify the cell densities in the explants nor the DNA contents, at any vector dose employed. In contrast, a dose-dependent increase in safranin O and type-II collagen staining intensities was noted when applying rAAV-FLAG-hsox9, as well as an augmentation of the proteoglycan and type-II collagen contents. The data show that sox9 overexpressed in normal human and osteoarthritic articular cartilage explants via rAAV promotes type-II collagen and matrix synthesis in situ, suggesting that rAAV may have value in enhancing the reparative properties of injured articular cartilage.
CORTICOTROPINS (ACTH)
Authors: Choh Hao Li, Peter Fønss-Bech, Irving I. Geschwind, Tetsuo Hayashida, Gerald F. Hungerford, Ardis J. Lostroh, William R. Lyons, Henry D. Moon, William O. Reinhardt, Martin Sideman
Journal: The Journal of Experimental Medicine (1957)

Purified alpha-corticotropin has been reported to exercise the following biological effects: (a) stimulation of the adrenal glands in normal and hypophysectomized rats, (b) production of blood eosinopenia in hypophysectomized rats, (c) maintenance of muscle glycogen in hypophysectomized rats, (d) inhibition of growth-promoting activity of somatotropin, (e) stimulation of melanocytes in the skin of frogs, (f) mobilization of fat into the liver of fasted mice, (g) stimulation of the accessory sex glands of castrated-hypophysectomized male rats, (h) induction of deciduoma formation in hypophysectomized-oophorectomized rats, and (i) elevation of the total red cell volume in hypophysectomized rats. alpha-Corticotropin has also been shown for the first time to act in synergism with lactogenic hormone as an essential galactopoietic hormone. The ability of alpha-corticotropin to elicit biological responses in the absence of the adrenal cortex is discussed.
The Irritable Bowel Syndrome: Review and a Graduated Multicomponent Treatment Approach
Authors: Douglas A. Drossman, W. Grant Thompson
Journal: Annals of Internal Medicine (1992)

The irritable bowel syndrome is a common chronic disorder having a broad clinical spectrum of severity. Although only a small proportion of those afflicted seek medical help for their symptoms, a subset have severe and intractable symptoms. A positive diagnosis should be established from the history and physical examination; endoscopic and radiologic investigations should be minimized. We suggest that the physician also assess the severity of the illness based on its symptomatic and functional features and the patient's behavioral response. Classifying the disorder in this manner permits a graduated treatment approach that emphasizes education, reassurance, and dietary adjustment for mild symptoms. Moderate symptom severity requires, in addition, identification and modification of factors exacerbating symptoms, psychotherapeutic and behavioral techniques and, if a certain symptom type predominates, pharmacologic agents directed toward the presumed gastrointestinal motor dysfunction. For severe symptoms, physician-based behavior modification and psychopharmacologic agents are helpful. When the disorder is intractable, referral may be needed, for example, to a pain treatment center. In all cases, the skillful physician must ensure continued psychosocial support to enhance coping and continued focus on the palliative aspects of care rather than on cure.
Serratia Vertebral Osteomyelitis in Narcotic Addicts
Authors: Lawrence Mintz, George H. Mollett
Journal: Annals of Internal Medicine (1975)

Letters1 November 1975Serratia Vertebral Osteomyelitis in Narcotic AddictsLAWRENCE MINTZ, M.D., GEORGE H. MOLLETT, M.D.LAWRENCE MINTZ, M.D.Search for more papers by this author, GEORGE H. MOLLETT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-5-668 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptHematogenous vertebral osteomyelitis is a well-documented complication of parenteral heroin use (1-3). In this setting, Gram-negative bacilli such asPseudomonas, Klebsiella, andEnterobacterhave replacedStaphylococcusaureus as the prevailing etiologic organisms. In a recent 12-month period, three long-term heroin addicts with vertebral osteomyelitis due toSerratia marcescenswere seen and treated at Mount Zion Hospital and Medical Center and at the San Francisco General Hospital, and we report their cases here.Serratia marcescensis a rare cause of orthopedic infections in general and, to our knowledge, has been reported only once previously as the cause of osteomyelitis in a...References1. HOLZMANBISHKO RF: Osteomyelitis in heroin addicts. Ann Intern Med 75:693-696, 1971 LinkGoogle Scholar2. LEWISGORBACHALTNER RSP: Spinal Pseudomonas chondro-osteomyelitis in heroin users. N Engl J Med 286:1303, 1972 CrossrefMedlineGoogle Scholar3. FISHBACHROSENBLATTDAHLGREN RJJ: Pyogenic vertebral osteomyelitis in heroin addicts. Calif Med 119:1-4, 1973 MedlineGoogle Scholar4. WILKOWSKEWASHINGTONMARTIN CJW: Serratia marcescens. Biochemical characteristics, antibiotic susceptibility patterns, and clinical significance. JAMA 214:2157-2162, 1970 CrossrefMedlineGoogle Scholar5. TUAZONHILLSHEAGREN CRJ: Microbiologic study of street heroin and injection paraphernalia. J Infect Dis 129:327-329, 1974 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNon-contiguous multifocal vertebral osteomyelitis caused by Serratia marcescensNon-contiguous multifocal vertebral osteomyelitis caused by Serratia marcescensClinical Assessment and Medical Treatment of Spine InfectionsSerratia Spondylodiscitis After Elective Lumbar Spine SurgeryBone and joint infections in injection drug usersSevere Flank Pain in an Intravenous User of CocaineVertebral OsteomyelitisHematogenous Serratia marcescens osteomyelitis of the carpal scaphoid from an indwelling radial artery catheterSerratia marcescensSerratia Marcescens in Human AffairsOpioid analgesics and narcotic antagonists 1 November 1975Volume 83, Issue 5Page: 668-669KeywordsAddictsEnterobacterHeroinHeroin useKlebsiellaOrthopedicsOsteomyelitisPseudomonasSerratia marcescensStaphylococcus aureus Issue Published: 1 November 1975 PDF DownloadLoading ...
Experimental Acute Myocardial Infarction
Authors: STEPHEN E. EPSTEIN, G. DAVID BEISER, DOUGLAS R. ROSING, JAMES V. TALANO, RICHARD B. KARSH
Journal: Circulation (1973)

The majority of deaths from acute myocardial infarction (AMI) occur prior to the arrival of medical aid and appear to be due to ventricular fibrillation (VF). Since the premature ventricular contraction and bradycardia are believed to predispose to VF, it has been suggested that administration of atropine or lidocaine during the prehospital phase of AMI may effectively reduce mortality in AMI. To test the efficacy of these drugs in treating arrhythmias during the acute phase of AMI we studied 72 closed-chest conscious dogs in which AMI was produced by inflating a balloon cuff previously implanted around the left anterior descending coronary artery. Ventricular arrhythmias developed in 52 dogs either during occlusion or within 2 min of release of occlusion. Arrhythmias were treated by (1) atropine, (2) atrial pacing, (3) lidocaine, or (4) atropine plus lidocaine. Of the 18 dogs that developed VF, all had ectopic ventricular beats that followed a preceding beat (R-R PVC interval) by ≤0.43 sec; no dog with a ventricular arrhythmia that exhibited only R-R PVC intervals &gt;0.43 sec developed VF. On this basis arrhythmias were defined as "benign" (R-R PVC &gt;0.43 sec) or "malignant" (R-R PVC ≤0.43 sec). Using this classification, we found that benign arrhythmias were successfully suppressed by atropine (10 of 13 arrhythmias), pacing (nine of 11), and lidocaine (three of five); however, atropine suppressed only two of 18, pacing two of 14, and lidocaine none of six malignant arrhythmias. We conclude that (1) not all ventricular arrhythmias are potentially lethal and (2) while atropine, pacing, and lidocaine successfully suppress most benign arrhythmias, they appear considerably less effective in suppressing those faster arrhythmias that frequently lead to the precipitation of VF.
The Duration of Activity in Acute Rheumatic Fever
Authors: Alvan R. Feinstein
Journal: JAMA (1961)

In 265 children and adolescents with rheumatic fever who were followed into and beyond the convalescent period, the average duration of acute inflammatory activity was 109 ±57 days. The average duration was significantly longer in patients who had valvular involvement (124 days) than in those who did not (89 days). In patients who received a relatively short course of anti-inflammatory treatment and who then had a posttherapeutic clinical rebound which was allowed to subside spontaneously, the total duration of rheumatic activity was almost identical to that found in patients whose entire attack had been untreated. These results suggest that the duration of rheumatic activity is prolonged by prolonged therapy but is unaffected when the original course of treatment is shorter than the natural course of the acute inflammation.
Hepatocellular carcinoma in primary biliary cirrhosis: An autopsy study
Authors: Yasuni Nakanuma, Tadashi Terada, Kenji Doishita, Atsushi Miwa
Journal: Hepatology (1990)

A survey of Japanese autopsy cases of primary biliary cirrhosis disclosed that hepatocellular carcinoma is apparently becoming a better recognized complication of the advanced stage of primary biliary cirrhosis. Six autopsy cases (five women and one man) of primary biliary cirrhosis associated with hepatocellular carcinoma were obtained from several Japanese institutions and examined. All cases were in an established cirrhotic stage of primary biliary cirrhosis. Hepatocellular carcinoma was incidentally found at autopsy in four cases and, in these, the carcinomas were small in size and number. The other two cases showed advanced hepatocellular carcinoma and one case showed extrahepatic metastasis. Histologically, all cases showed well-differentiated hepatocellular carcinomas. Fatty changes or bile plugs were frequently seen within the tumors. Mallory body clusters and focal deposition of copper-binding protein were consistently found in cirrhotic liver tissues and also in the carcinoma tissues of almost all cases. The presence of atypical adenomatous hyperplasia in the peripheries of some carcinomas suggested that hepatocellular carcinoma in primary biliary cirrhosis may evolve through multiple steps.
Lung Cancer Screening With Helical Computed Tomography in Older Adult Smokers
Authors: Parthiv J. Mahadevia, Lee A. Fleisher, Kevin D. Frick, John Eng, Steven N. Goodman, Neil R. Powe
Journal: JAMA (2003)

<h3>Context</h3> Encouraged by direct-to-consumer marketing, smokers and their physicians are contemplating lung cancer screening with a promising but unproven imaging procedure, helical computed tomography (CT). <h3>Objective</h3> To estimate the potential benefits, harms, and cost-effectiveness of lung cancer screening with helical CT in various efficacy scenarios. <h3>Design, Setting, and Population</h3> Using a computer-simulated model, we compared annual helical CT screening to no screening for hypothetical cohorts of 100 000 current, quitting, and former heavy smokers, aged 60 years, of whom 55% were men. We simulated efficacy by changing the clinical stage distribution of lung cancers so that the screened group would have fewer advanced-stage cancers and more localized-stage cancers than the nonscreened group (ie, a stage shift). Our model incorporated known biases in screening programs such as lead time, length, and overdiagnosis bias. <h3>Main Outcome Measures</h3> We measured the benefits of screening by comparing the absolute and relative difference in lung cancer–specific deaths. We measured harms by the number of false-positive invasive tests or surgeries per 100 000 and incremental cost-effectiveness in US dollars per quality-adjusted life-year (QALY) gained. <h3>Results</h3> Over a 20-year period, assuming a 50% stage shift, the current heavy smoker cohort had 553 fewer lung cancer deaths (13% lung cancer–specific mortality reduction) and 1186 false-positive invasive procedures per 100 000 persons. The incremental cost-effectiveness for current smokers was $116 300 per QALY gained. For quitting and former smokers, the incremental cost-effectiveness was $558 600 and $2 322 700 per QALY gained, respectively. Other than the degree of stage shift, the most influential parameters were adherence to screening, degree of length or overdiagnosis bias in the first year of screening, quality of life of persons with screen-detected localized lung cancers, cost of helical CT, and anxiety about indeterminate nodule diagnoses. In 1-way sensitivity analyses, none of these parameters was sufficient to make screening highly cost-effective for any of the cohorts. In multiway sensitivity analyses, a program screening current smokers was $42 500 per QALY gained if extremely favorable estimates were used for all of the influential parameters simultaneously. <h3>Conclusion</h3> Even if efficacy is eventually proven, screening must overcome multiple additional barriers to be highly cost-effective. Given the current uncertainty of benefits, the harms from invasive testing, and the high costs associated with screening, direct-to-consumer marketing of helical CT is not advisable.
Ethanol sensitivity of the GABAA receptor expressed in xenopus oocytes requires 8 amino acids contained in the γ2L subunit
Authors: Keith A. Wafford, Donald M. Burnett, Nancy J. Leidenheimer, David R. Burt, Jia Bei Wang, Paulo Kofuji, Thomas V. Dunwiddie, R.Adron Harris, James M. Sikela
Journal: Neuron (1991)