tbuckley/cabot-search huggingface dataset:
Issues in Research with Human Subjects
Authors: E. C. Huskisson
Journal: Annals of the Rheumatic Diseases (1981)

Research in human subjects is very important.Apart from the study of disease there is now a widespread acceptance of the view that treatment can be shown to be effective only by controlled clinical trials.This brings physicians to give their patients dummy tablets, to deny them active treatment, and to fail to tell them what is going on.What patient would continue to take dummy tablets if he knew what they were?The surface of this important subject is gently stroked but not scratched in this little book, and it is probably good to remind clinical investigators of their moral obligations from time to time.Relations with regulatory authorities are also discussed, and the British investigator will be pleased to know, from an inside source, that the FDA will not reject his 'foreign data' just because they are 'foreign'.They may not be regarded as 'pivotal,' since it appears that 'foreign' investigators are reluctant to supply case records or report forms to support the honesty and integrity of their work.A continued deep suspicion of foreigners, and their work is clearly justified.Jargon abounds in this publication.Could FDA, for example, give NDA, or could CSM grant NPL in NIH funded REC approved NHLBI CT of BO under HEW regulations using SSN for FECA at RBH? Words do not necessarily help.Once paper concludes that 'multicentre clinical trials require a synthesis of the scientific method and the precepts of modern management.'Among a few very enjoyable and stimulating contributions is a paper on randomised controlled trials of nonpharmacological treatment.This would be enormously helpful to a young physician who wanted to do some research but could not think of a worthwhile project.Much of what physicians and surgeons do is empirical but could be randomised and documented.Though there
Familial thrombosis: inherited deficiency of antithrombin III.
Authors: M Mackie, B Bennett, D Ogston, A S Douglas
Journal: BMJ (1978)

Several members of a family living on the west coast of Scotland and on one of the islands off the coast had serious thrombotic disease. The plasma antithrombin III (ATIII) concentrations were measured by both functional and immunological assay in all available members of the family. Concentrations were 25% to 66% of normal in 12 people, including all seven with thrombotic disease. The inheritance pattern was characteristic of an autosomal dominant disorder. Thrombotic disease generally affected the leg, mesenteric, and axillary veins, although one man who had died before the study began had had severe arterial atheroma. In women the first thrombotic symptoms usually occurred during pregnancy. None of these patients have developed thrombotic symptoms until they were at least 18, so four younger members of the family who have ATIII deficiency but no thrombotic disease may eventually develop symptoms.
Reduced Lung Function at Birth and the Risk of Asthma at 10 Years of Age
Authors: Geir Håland, Karin C. Lødrup Carlsen, Leiv Sandvik, Chandra Sekhar Devulapalli, Monica Cheng Munthe-Kaas, Morten Pettersen, Kai-Håkon Carlsen
Journal: New England Journal of Medicine (2006)

Reduced lung function in early infancy has been associated with later obstructive airway diseases. We assessed whether reduced lung function shortly after birth predicts asthma 10 years later.We conducted a prospective birth cohort study of healthy infants in which we measured lung function shortly after birth with the use of tidal breathing flow-volume loops (the fraction of expiratory time to peak tidal expiratory flow to total expiratory time [t(PTEF)/t(E)]) in 802 infants and passive respiratory mechanics, including respiratory-system compliance, in 664 infants. At 10 years of age, 616 children (77%) were reassessed by measuring lung function, exercise-induced bronchoconstriction, and bronchial hyperresponsiveness (by means of a methacholine challenge) and by conducting a structured interview to determine whether there was a history of asthma or current asthma.As compared with children whose t(PTEF)/t(E) shortly after birth was above the median, children whose t(PTEF)/t(E) was at or below the median were more likely at 10 years of age to have a history of asthma (24.3% vs. 16.2%, P=0.01), to have current asthma (14.6% vs. 7.5%, P=0.005), and to have severe bronchial hyperresponsiveness, defined as a methacholine dose of less than 1.0 micromol causing a 20% fall in the forced expiratory volume in 1 second (FEV1) (9.1% vs. 4.9%, P=0.05). As compared with children whose respiratory-system compliance was above the median, children with respiratory compliance at or below the median more often had a history of asthma (27.4% vs. 14.8%; P=0.001) and current asthma (15.0% vs. 7.7%, P=0.009), although this measure was not associated with later measurements of lung function. At 10 years of age, t(PTEF)/t(E) at birth correlated weakly with the maximal midexpiratory flow rate (r=0.10, P=0.01) but not with FEV1 or forced vital capacity.Reduced lung function at birth is associated with an increased risk of asthma by 10 years of age.
The Immunization and Tuberculin-Testing Status of Certain Selected Families
Authors: Roger J. Meyer, Robert J. Haggerty
Journal: New England Journal of Medicine (1961)

MANY families and some physicians seem to have been lulled into a false sense of security regarding their health by the advent of so-called "miracle drugs," new vaccines, more hygienic living conditions and comprehensive insurance plans. They frequently forget the continuing need for routine immunizations and tuberculosis testing. As an example, within the past year we have observed an unimmunized grandmother living in Boston with her children and grandchildren in whom diphtheria developed. Despite this, some members of the family were not subsequently immunized.In an effort to teach medical students the importance of maintaining commonly accepted health-protection measures in . . .
THE TERMINATION OF IMMUNOLOGICAL UNRESPONSIVENESS TO BOVINE SERUM ALBUMIN IN RABBITS
Authors: D. C. Benjamin, W. O. Weigle
Journal: The Journal of Experimental Medicine (1970)

Rabbits made unresponsive to BSA at birth were given two courses of immunization with various cross-reacting albumins at 3 months of age. Normal control rabbits, of equivalent age and weight, were similarly immunized. Sera obtained 7 days after the last injection were assayed for binding and precipitating antibody to six albumins and for their avidity for BSA. No significant differences were found between unresponsive and normal rabbits in the amount of antibody reacting with any of the six albumins used. This was the case regardless which albumin was used to terminate the unresponsive state. Avidity differences were seen and seemed to depend on the antigen used and not on the immunological status of the animal. The simultaneous injection of small amounts of BSA inhibited the termination of unresponsiveness. These results were discussed in the light of the more recent theories of the termination of unresponsiveness and of antibody formation.
Being sanguine about study design and multiple imputation
Authors: S. M. Bird
Journal: BMJ (2012)

Using The Health Improvement Network (THIN) database, Collins and Altman validate QRISK2-2011 versus the National Institute for Health and Clinical Excellence’s Framingham Equation (NFE) for predicting 10 year risk of cardiovascular disease.1

The QRISK2-2011 web calculator replaces missing data via multiple imputation predictor algorithms. Would I want my risk assessed on imputed data or prefer my GP to determine which data to obtain? …
An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. Its influence on glycoprotein IIb-IIIa complex function.
Authors: P Nurden, P Savi, E Heilmann, C Bihour, J M Herbert, J P Maffrand, A Nurden
Journal: Journal of Clinical Investigation (1995)

Much discussion has concerned the central role of ADP in platelet aggregation. We now describe a patient (M.L.) with an inherited bleeding disorder whose specific feature is that ADP induces a limited and rapidly reversible platelet aggregation even at high doses. Platelet shape change and other hemostatic parameters were unmodified. A receptor defect was indicated, for, while epinephrine normally lowered cAMP levels of PGE1-treated (M.L.) platelets, ADP was without effect. The binding of [3H]2-methylthio-ADP decreased from 836 +/- 126 molecules/platelet for normals to 30 +/- 17 molecules/platelet for the patient. Flow cytometry confirmed that ADP induced a much lower fibrinogen binding to (M.L.) platelets. Nonetheless, the binding in whole blood of activation-dependent monoclonal antibodies showed that some activation of GP IIb-IIIa complexes by ADP was occurring. Platelets of a patient with type I Glanzmann's thrombasthenia bound [3H]2-methylthio-ADP and responded normally to ADP in the presence of PGE1. Electron microscopy showed that ADP-induced aggregates of (M. L.) platelets were composed of loosely bound shape-changed platelets with few contact points. Thus this receptor defect has a direct influence on the capacity of platelets to bind to each other in response to ADP.
Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration
Authors: M. Fujiwara, Y. Muragaki, A. Ooshima
Journal: British Journal of Dermatology (2005)

A keloid is a specific skin lesion that expands beyond the boundaries of the original injury as it heals. Histologically, it is characterized by the excessive accumulation of collagen. However, the reasons for the expansion and the invasive nature of keloids remain unknown.We evaluated collagen degradation and migration by cultured keloid fibroblasts based on the assumption that these variables were of functional relevance to the expanding and invasive nature of keloid lesions.Collagen production was investigated by the detection of type 1 collagen (procollagen type 1C peptide: P1P). Matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-2 (gelatinase-A), were investigated as elements of the collagen degradation system. Enzyme immunoassays were performed to measure the production of P1P, MMP-1, MMP-2, and tissue inhibitor of metalloproteinase (TIMP)-1. To assess the production of MMP-2 its gelatinolytic activity was measured by zymography using gelatin-containing gels. The participation of transforming growth factor-beta1 (TGF-beta1) in the production and degradation of collagen was also investigated. Finally, the migratory activity of keloid fibroblasts was evaluated using a colony dispersion assay.The production of type 1 collagen, MMP-1, MMP-2, and TIMP-1 by keloid fibroblasts was 3-fold, 6-fold, 2.4-fold, and 2-fold greater than that of normal dermal fibroblasts, respectively. Production of P1P was increased when TGF-beta1 was added to cultures of keloid fibroblasts, while it was decreased when anti-TGF-beta1 antibody was added to the cultures. In contrast, the production of MMP-1 was decreased by the addition of TGF-beta1 to cultured keloid fibroblasts, while it was increased when anti-TGF-beta1 antibody was added to the cultures. The production of MMP-2 increased after treatment with TGF-beta1, but did not change significantly when anti-TGF-beta1 antibody was added to the cultures. Production of TIMP-1 did not change significantly when either TGF-beta1 or anti-TGF-beta1 antibody was added to the cultures. Keloid fibroblasts showed a 2.5-fold increase of migratory activity compared with normal dermal fibroblasts, while the migratory activity of these fibroblasts was reduced to the control level by treatment with a broad-spectrum MMP inhibitor (GM 6001).Cultured keloid fibroblasts showed increased production of collagen and MMPs, and TGF-beta1 played a role in this regulation of production. In addition, increased production of MMPs had a role in the high migratory activity of cultured keloid fibroblasts.
Activation of Blood Coagulation After Cardiac Arrest Is Not Balanced Adequately by Activation of Endogenous Fibrinolysis
Authors: Bernd W. Böttiger, Johann Motsch, Hubert Böhrer, Thomas Böker, Michael Aulmann, Peter P. Nawroth, Eike Martin
Journal: Circulation (1995)

Background Animal studies have demonstrated that hemostatic disorders occurring after cardiac arrest affect outcome. We investigated hemostatic changes during and after cardiopulmonary resuscitation (CPR) in humans. Methods and Results The prospective study included 23 patients (29 to 86 years) who underwent out-of-hospital CPR for nontraumatic causes. Blood samples were drawn immediately and 15 and 30 minutes after initiation of CPR. In the case of restoration of spontaneous circulation (ROSC; n=7), additional blood samples were taken immediately, 30 minutes, and 2, 8, 24, 48, and 72 hours after ROSC. A marked activation of blood coagulation was found in all patients. The specific markers of activated blood coagulation and fibrin formation, thrombin-antithrombin complex (TAT; median during CPR, 260 μg/L; median after ROSC, 57 μg/L; normal range, 1.0 to 4.1 μg/L), and fibrin monomers (FM; median during CPR, 34.3 μg/mL; median after ROSC, 65.4 μg/mL; normal range, 0 to 3.6 μg/mL) were markedly increased during and in the early phase after CPR. When patients survived for 48 hours, TAT and FM values returned to the normal range. In most patients, the plasma levels of d -dimer, an indicator of endogenous fibrinolytic activity, were not markedly increased during CPR (median, &lt;0.25 μg/mL; normal range, &lt;0.25 μg/mL) but increased moderately after ROSC (median, 0.56 μg/mL). Levels of plasminogen activator inhibitor type 1 (normal range, 0.3 to 3.5 U/mL), a marker for endogenous inhibition of fibrinolytic activity, were moderately increased in most patients (median during CPR, 4.22 U/mL; median after ROSC, 8.08 U/mL). Conclusions Our data clearly demonstrate that there is a marked activation of blood coagulation and fibrin formation after prolonged cardiac arrest and CPR in humans that is not balanced adequately by concomitant activation of endogenous fibrinolysis. These changes may contribute to reperfusion disorders, such as the cerebral “no-reflow” phenomenon, by inducing fibrin deposition and formation of microthrombi.
Combination Antibiotic Therapy of Bacterial Endocarditis
Authors: PHILIP C. CRAVEN
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 August 1980Combination Antibiotic Therapy of Bacterial EndocarditisPHILIP C. CRAVEN, M.D., DAVID J. DRUTZ, M.D., DWIGHT M. WILLIAMS, M.D., JOHN R. GRAYBILL, M.D.PHILIP C. CRAVEN, M.D.Search for more papers by this author, DAVID J. DRUTZ, M.D.Search for more papers by this author, DWIGHT M. WILLIAMS, M.D.Search for more papers by this author, JOHN R. GRAYBILL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-2-376_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: "Combination Antibiotic Therapy of Bacterial Endocarditis" by Sande and Scheid (1) concisely and usefully summarizes several controversial areas in endocarditis treatment. We are concerned, however, that several of the recommendations poorly supported by evidence may lead to widespread use of potentially suboptimal regimens:Enterococcal Endocarditis, 4 weeks versus 6 weeks:In the absence of a comparative study, it is not clear why Mandell's carefully studied series of 38 patients supporting 6 weeks of therapy ("early, anecdotal, clinical experience and retrospective studies") should be less persuasive than the series of 13 patients and the unpublished communication cited in...References1. SANDESCHELD MW. Combination antibiotic therapy of bacterial endocarditis. Ann Intern Med. 1980;92:390-5. LinkGoogle Scholar2. DREYERFIELDS NB. Heroin-associated infective endocarditis: a report of 28 cases. Ann Intern Med. 1973;78:699-702. LinkGoogle Scholar3. NEUFIELDBRANSONMARSHALLBANKSALI GCLTN. Infective endocarditis as a complication of heroin use. South Med J. 1976;69:1148-51. CrossrefMedlineGoogle Scholar4. BANKSFLETCHERALI TRN. Infective endocarditis in heroin addicts. Am J Med. 1973;55:444-51. CrossrefMedlineGoogle Scholar5. CHERUBINBADENKAVALERLERNERCLINE CMFSW. Infective endocarditis in narcotic addicts. Ann Intern Med. 1968;69:1091-8. LinkGoogle Scholar6. CARRIZOSAKAYE JD. Antibiotic concentrations in serum, serum bactericidal activity, and results of therapy of streptococcal endocarditis in rabbits. Antimicrob Agents Chemother. 1977;12:479-83. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The University of Texas Health Science Center San Antonio, TX 78284 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCombination Antimicrobial Therapy 1 August 1980Volume 93, Issue 2Page: 376-376KeywordsAntibioticsEndocarditisRetrospective studies Issue Published: 1 August 1980 PDF DownloadLoading ...
Global versus regional myocardial ischaemia: differences in cardiovascular and sympathetic responses in cats
Authors: F. LOMBARDI, C. CASALONE, G. MALFATTO, M. PAGANI, A. MALLIANI
Journal: Cardiovascular Research (1984)

The cardiovascular and sympathetic responses to occlusions of the left main ("global" ischaemia) or distal left anterior descending ("regional" ischaemia) coronary artery were studied in 19 anaesthetised cats with chronic sinoaortic baroreceptor denervation. "Global" ischaemia, before vagotomy, resulted in a significant reduction of mean arterial pressure (MAP), left ventricular pressure (LVP), and LVdP/dtmax while sympathetic efferent impulse activity was significantly augmented during the initial 15±2 s of occlusion (early phase) and, vice versa inhibited during the subsequent 20±2 s of occlusion (late phase). Vagotomy did not modify the haemodynamic responses, however, a significant increase in sympathetic discharge was detectable during the whole occlusion period (early and late phases). "Regional" ischaemia, before vagotomy, resulted in a significant increase in sympathetic neural discharge and MAP, with no changes in left ventricular function. After vagotomy the occlusion elicited a significant increase in MAP, LVP, LVdP/dtmax and efferent sympathetic neural activity. These excitatory responses were abolished after the interruption of a large part of the cardiac sympathetic afferents. Thus coronary artery occlusion induced haemodynamic and sympathetic reflex responses that were dependent upon the interaction of opposite influences mediated by the simultaneous activation of cardiac vagal and sympathetic afferents. The extent of "ischaemic myocardium" represented a determinant factor for the prevailing type of neural response.
Abstract P1-01-24: Is the Dye Method Alone Useful for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer? Prospective Analysis of 1081 Patients after SLN Biopsy
Authors: T Iwase, R Nakamura, Y Naohito, F Kouya, O Toshi, M. Miyazaki
Journal: Cancer Research (2010)

Abstract Introduction: Sentinel lymph node biopsy (SLNB) for breast cancer has been established. The objective of this study was to investigate factors which elevate the identification rate employing the dye method (DYm) alone. Subjects: The subjects were 1,081 cN0 breast cancer patients who underwent preoperative cytology of the axillary lymph nodes at our facility between May 2001 and April 2010. Methods: In the morning of the operation day, 0.3 ml of technetium phytate was subcutaneously injected immediately above the tumor, and 5 ml of indigocarmine was subcutaneously injected into the para-areolar region on the axillary side immediately before surgery, attempting to identify sentinel lymph nodes (SLN) using the combination method. The rates of identification employing the DYm and RI method (Rim) and false-negative rates were calculated. Regarding SLN in which the highest count was detected by the RIm as the first SLN (fSLN), consistency with that detected using the DYm was investigated. Results: The mean numbers of SLN identified by the DYm and RIm were 1.36 and 1.90, respectively, showing that significantly more lesions were identified employing the RIm (P&amp;lt;0.05). The identification rates employing the dye, RI, and both methods were 88.7, 98.7, and 99.3%, respectively, and the consistency of fSLN between the DYm and RIm was 78.1%. SLN metastasis detected using the RIm could not be identified employing the dye method in 20 cases. The age, tumor size, and BMI were investigated in these 20 cases, and a significant difference was noted in the tumor size. Conclusion: The identification rate employing the DYm alone was lower than that employing the RIm. The consistency of fSLN between the two methods was 78.1%. Although the RIm may have biopsied excess lymph nodes (LN), its use may be important to complement the DYm. Dye does not readily enter metastatic LN because of the presence of tumor plugs. The application of preoperative axillary LN cytology to cases with large tumors to exclude metastasis-positive cases may elevate the SLN identification rate employing the DYm. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-24.
Phaeochromocytoma: an unusual cause of chest pain.
Authors: P McGonigle, S W Webb, A A Adgey
Journal: BMJ (1983)

tory nerve endings were larger than usual, particularly on the right.The whole of the bone of the cribriform plate was paper thin and mobile.The defect was closed with a fascia lata patch obtained from the thigh.Post- operative recovery was uneventful.Histology of the olfactory bulb showed chronic inflammatory change and gliosis. CommentsCocaine is a psychologically addictive drug and its abuse is greatly increasing.3It is derived from the coca leaf and is used as a local anaes- thetic in otolaryngology because of its useful vasoconstrictor activity.The mechanism of this effect is by inhibiting reuptake of catechola- mines into the sympathetic nerve ending, thus potentiating their effect.4Chronic abuse of the drug by intranasal sniffing may lead to chronic inflammatory changes and perforation of the nasal septum, owing to the effects of intense vasoconstriction.5 Similar chronic damage prob- ably resulted in the changes in the cribriform plate and olfactory nerves in our patient, which ultimately lead to a leak of cerebrospinal fluid.
Milestones in the Curability of Pediatric Cancers
Authors: Melissa M. Hudson, Michael P. Link, Joseph V. Simone
Journal: Journal of Clinical Oncology (2014)

Progress in the study and treatment of childhood cancer is arguably the most remarkable and rewarding story of cancer therapy in the past five decades. During this time, five-year survival rates have steadily increased and now exceed 80% in developed countries for all pediatric cancer sites (Fig 1). With the expectation of extended survival into adulthood for most childhood patients with cancer, clinicians and researchers have concentrated considerable attention on optimizing the quality of long-term survival for diseases that largely respond to cytotoxic agents and modalities injurious to normal tissues. In this recollection of that progress, we shall touch on advances common to many childhood cancers but focus primarily on childhood leukemia because it has been the bellwether of scientific and therapeutic advances in many tumors, it encompasses many novel ideas in patient care during and after therapy, and it has influenced the study and treatment of adult cancers as well.