tbuckley/cabot-search huggingface dataset:
Remembering Medicine's Past
Authors: Barron H. Lerner
Journal: Annals of Internal Medicine (1998)

Currents15 September 1998Remembering Medicine's PastBarron H. Lerner, MD, PhDBarron H. Lerner, MD, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-6-199809150-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Being poor is watching all the residents passing a laryngoscope down your dead baby's throat … Being poor is having four young men put their fingers in your vagina, and only one of them has his name end in MD.” Writing in 1969, a Philadelphia medical student used these words to describe how urban teaching hospitals treated poor patients as nothing more than “educational material.”This critique of medical education was recalled by Yale University historian Naomi Rogers at the 71 st annual meeting of the American Association for the History of Medicine (AAHM), held in Toronto from 7 to ... Author, Article, and Disclosure InformationAuthors: Barron H. Lerner, MD, PhD Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1998Volume 129, Issue 6Page: 515-516KeywordsAIDSChild healthGraduate medical educationHistory of medicineMedical educationPharynxPlaguePrevention, policy, and public healthSleepVagina ePublished: 15 August 2000 Issue Published: 15 September 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein c reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation.
Authors: P Gresele, S Momi, M Berrettini, G G Nenci, H P Schwarz, N Semeraro, M Colucci
Journal: Journal of Clinical Investigation (1998)

Activated protein C (APC) is a potent physiologic anticoagulant with profibrinolytic properties, and has been shown to prevent thrombosis in different experimental models. We investigated the effect of human APC on thrombin-induced thromboembolism in mice, a model of acute intravascular fibrin deposition leading to death within minutes. APC given intravenously (i.v.) as a bolus 2 min before thrombin challenge (1,250 U/kg) reduced mortality in a dose-dependent manner despite the lack of thrombin inhibitor activity. Significant inhibition of thrombin-induced death was observed at the dose of 0.05 mg/kg, and maximal protection was obtained with 2 mg/kg (> 85% reduction in mortality rate). Histology of lung tissue revealed that APC treatment (2 mg/kg) reduced significantly vascular occlusion rate (from 89.2 to 46.6%, P < 0.01). The protective effect of APC was due to the inhibition of endogenous thrombin formation as indicated by the fact that (a) the injection of human thrombin caused a marked decrease in the coagulation factors of the intrinsic and common pathways (but not of Factor VII), suggesting the activation of blood clotting via the contact system; (b) APC pretreatment reduced markedly prothrombin consumption; (c) the lethal effect of thrombin was almost abolished when the animals were made deficient in vitamin K-dependent factors by warfarin treatment, and could be restored only by doubling the dose of thrombin, indicating that the generation of endogenous thrombin contributes significantly to death; and (d) APC failed to protect warfarin-treated animals, in which mortality is entirely due to injected thrombin, even after protein S supplementation. Other results suggest that APC protects from thrombin-induced thromboembolism by rendering the formed fibrin more susceptible to plasmin degradation rather than by reducing fibrin formation: in thrombin-treated mice, fibrinogen consumption was not inhibited by APC; and inhibition of endogenous fibrinolysis by epsilon-aminocaproic or tranexamic acid resulted in a significant reduction of the protective effect of APC. Since APC did not enhance plasma fibrinolytic activity, as assessed by the measurement of plasminogen activator (PA) or PA inhibitor (PAI) activities, PAI-1 antigen, or 125I-fibrin degrading activity, we speculate that the inhibition of additional (endogenous) thrombin formation by APC interrupts thrombin-dependent mechanisms that make fibrin clots more resistant to lysis, so that the intravascular deposited fibrin can be removed more rapidly by the endogenous fibrinolytic system.
Corrigendum to: “Functional and Histological Changes after Myoblast Injections in the Porcine Rhabdosphincter” [Eur Urol 2007;52:1736–43]
Authors: Michael Mitterberger, Germar M. Pinggera, Rainer Marksteiner, Eva Margreiter, Raffael Plattner, Günter Klima, Hannes Strasser
Journal: European Urology (2008)
Auranofin in the treatment of steroid dependent asthma: a double blind study.
Authors: G Nierop, W P Gijzel, E H Bel, A H Zwinderman, J H Dijkman
Journal: Thorax (1992)

BACKGROUND: Long term administration of oral corticosteroids in patients with asthma may be associated with serious side effects. Non-steroidal anti-inflammatory drugs, including gold salts, have been shown to reduce the need for systemic corticosteroid treatment in uncontrolled studies. The effect of oral gold (auranofin) on asthma symptoms, lung function, and the need for oral prednisone treatment was investigated. METHODS: A 26 week randomised, double blind, placebo controlled, parallel group trial of auranofin was performed in 32 patients with moderately severe chronic asthma who required an oral corticosteroid dose of at least 5 mg prednisone a day (or equivalent) or 2.5 mg/day prednisone plus more than 800 micrograms/day inhaled corticosteroids. Auranofin was given orally in a dose of 3 mg twice daily. Asthma symptoms, lung function, and adverse effects were assessed at regular intervals. After 12 weeks of treatment prednisone dosage was tapered down by 2.5 mg every two weeks if the patient was clinically stable. Asthma exacerbations were treated with short courses of high doses of oral steroids. RESULTS: Twenty eight of the 32 patients, 13 in the placebo group and 15 in the auranofin group, completed the study. The total corticosteroid reduction achieved after 26 weeks of treatment was significantly greater (4 mg) in the auranofin group than in the placebo group (0.3 mg). The number of exacerbations requiring an increase of steroids was greater in the placebo group (2.1) than in the active group (0.9). A significant increase in FEV1 of 6.4% predicted occurred in the auranofin group during the study and there was a reduction of asthma symptoms such as wheezing and cough. There was no difference between the groups in peak flow measurements or in the number of asthma attacks. The incidence of side effects of auranofin was low, but exacerbations of constitutional eczema were noticeable. CONCLUSION: Auranofin provides an effective adjunct to treatment for steroid dependent asthma, leading to a reduction of oral steroid dose.
Association Between Glutathione S-Transferase M1, P1, and T1 Genetic Polymorphisms and Development of Breast Cancer
Authors: Kathy J. Helzlsouer, Han-Yao Huang, Sandra Hoffman, Anthony J. Alberg, George W. Comstock, Paul T. Strickland, Ornella Selmin, Mary Watson, Douglas Bell
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer. Methods: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22–3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95%CI = 1.34–4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77–5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95% CI = 0.76–2.95). The risk of breast cancer increased as the number of putative highrisk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10–12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity). Conclusions: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.
Samuel A. Mudd
Authors: Edward Shapiro
Journal: New England Journal of Medicine (1958)

IT is reasonable to assume that a noble profession should generate nobility in its practitioners. The life of Samuel A. Mudd, M.D., bears out this assumption. Because he was a physician, he was drawn afield as a co-conspirator in the assassination of President Abraham Lincoln. The same physicianly attributes redeemed his later life and regained him his freedom.Samuel A. Mudd was born on December 20, 1833, near Bryantown, Maryland, on the 500-acre plantation of his wealthy father. The sumptuous residence contained within itself both a schoolroom and a chapel. Young Mudd spent many years at school — two years . . .
Involvement of Proprietary Chains in Academic Health Centers
Authors: Anthony Reading
Journal: New England Journal of Medicine (1985)

The past 15 years have witnessed major changes in the organization and financing of medical care and education in the United States, reflecting changes in the national economy, biomedical technology, government policy, and social organization.1 It is likely that the structuring of the nation's medical system will change even further before stability is again achieved. One of the more dramatic changes during this period has been the rapid emergence of a large and growing network of private corporations engaged in the business of providing health care services to patients for profit — a territory traditionally occupied by public and nonprofit . . .
Seriously injured patients may suffer under new rules on litigation, MPs say
Authors: C. Dyer
Journal: BMJ (2011)

Adoptive transfer of diabetes was accomplished by the injection of Con A-activated acutely diabetic BB/W rat spleen cells into immunosuppressed diabetes-resistant BB/W control rats and F1 hybrid offspring produced by BB/W X Lewis, BN, Yashida, and NEDH matings. Immune suppression methods that facilitated adoptive transfer of diabetes included neonatal thymectomy, cyclophosphamide, and splenectomy plus rabbit anti-rat lymphocyte serum injections. The successful transfer of BB/W diabetes to otherwise normal (BB/W X inbred)F1 rats and to diabetes-resistant BB/W animals suggests that antigenically normal pancreatic beta cells were destroyed by the injected effector cells. Diabetes-resistant BB/W control rats also evidenced diabetes after the injection of cyclophosphamide alone. The requirement for immunosuppression suggests that an intact immune system protects against adoptive transfer and diabetes in diabetes-resistant BB/W rats.
The Relationship of the ABO Blood Groups to Duodenal and Gastric Ulceration
Authors: C. A. Clarke, W. K. Cowan, J. W. Edwards, A. W. Howel-Evans, R. B. McConnell, J. C. Woodrow, P. M. Sheppard
Journal: BMJ (1955)

The above body of data provided excellent material whereby the degree of correlation between the responses of infants to two very dissimilar antigens could be calculated.Calculations with combined and separate groups in both cases give a correlation coefficient r of <0.1 and P of >0.4.(Since the distribution of responses to both antigens is log normal all calculations were made on logs of titres.)This signifies a complete absence of relationship between the human infant's responsiveness to diphtheria toxoid and to the agglutinogen of H. pertussis vaccine. SummaryTwo similar groups of urban infants (Barking, Essex) aged from 2 to 5 months inclusive at time of first injec- tion were immunized against diphtheria and whooping- cough in different ways: (a) A course of three injections of combined prophylactic (W.D.P.-red). (b) A sepa- rate course of five injections: the course of three injec- tions of suspended pertussis vaccine (Glaxo) preceding that of two doses of diphtheria prophylactic P.T.A.P.All injections were made at monthly intervals, each child was bled at 15 months of age, and the sera were assayed for their diphtheria antitoxin and H. pertussis agglutina- tion titres.Three doses of the combined prophylactic-W.D.P. (red)-gave significantly higher antitoxin titres than those previously reported for two doses of A.P.T.It is note- worthy that the very young infants inoculated with the combined prophylactic gave higher antitoxin titres than somewhat older ones given A.P.T. Two doses Of P.T.A.P., however, gave the highest figures.Although whooping-cough vaccines of different manu- facture and H. pertussis content were used in the two groups the titres obtained were of the same order, and showed no significant difference.No correlation was found between the responses of individuals to the diphtheria toxoid and the H. pertussis agglutinogen.We gratefully acknowledge the help of other medical officers who assisted with the injections, and that of the health visitors in persuading parents to include their children in the research, as well as for the important part they are playing in the clinical follow-up.We have received invaluable assistance from Mr. Brian in the collection of blood specimens, and a considerable amount of clerical assistance from Mrs. Joan Saul.Thanks are also due to Mrs. Ann Watts for her help in the serum titrations.
Folic Acid in Folate-deficient Patients with Epilepsy
Authors: R. H. E. Grant, O. P. R. Stores
Journal: BMJ (1970)

A double-blind trial using folic acid 15 mg. daily and identical placebo was carried out in 51 epileptic patients having a serum folate level below 3·6 ng./ml. Treatment was for a minimum of six months and in 41 patients was for more than one year. There were no significant changes in the frequency of seizures, behaviour, and personality, or in a number of cognitive functions.
THE CORRELATION OF A BIPHASIC METABOLIC RESPONSE WITH A BIPHASIC RESPONSE IN RESISTANCE TO TUBERCULOSIS IN RABBITS
Authors: Marvin J. Allison, Peter Zappasodi, Max B. Lurie
Journal: The Journal of Experimental Medicine (1962)

We have found a phase of susceptibility associated with a reduced metabolic activity on the part of peritoneal mononuclear phagocytes taken from BCG-vaccinated rabbits. A second stage of heightened resistance to infection was found to be associated with a heightened metabolic activity. The period of susceptibility in BCG vaccination is primarily concerned with initiation of the infection and not with the progression of the disease, which in both stages is increased. These reactions are discussed in relation to other conditions, such as nonspecific protein therapy and the administration of endotoxin, which also have similiar biphasic stages of resistance. Of incidental interest is the fact that rabbits who received 400 roentgen units are two years later still unable to respond to BCG vaccination with an increase in resistance. We conclude that there is a relationship between the level of certain metabolic activities of reticuloendothelial cells and resistance to tuberculosis.
A study of oil of bergamot and its importance as a phototoxic agent.
Authors: S.T. ZAYNOUN, B.E. JOHNSON, W. FRAIN-BELL
Journal: British Journal of Dermatology (1977)

It is important in the technique of photopatch testing, using oil of bergamot, to have determined the concentration of the active psoralen, bergapten, so as to avoid false negative responses in the assessment of phototoxic reactions. Techniques for assessing the phototoxic components of oil of bergamot are described and quantitative analyses of bergapten, the only significant photoactive compound in the samples examined, are reported. The phototoxicity of bergapten was found to be nearly the same as that of xanthotoxin (8-MOP) in tests on human skin.
Gastric enzymes as a screening test for gastric cancer.
Authors: P J Finch, F P Ryan, K Rogers, S Holt
Journal: Gut (1987)

Levels of lactic dehydrogenase and beta-glucuronidase were measured in gastric wash samples obtained from 445 patients over 40 years old attending a routine diagnostic endoscopy clinic. An index was derived from the two levels and used as a test for the presence of gastric cancer. Of the 24 patients with an endoscopic diagnosis of gastric cancer, 21 (91.3%) proved positive on this test, including all four cases of early gastric cancer, which were found at repeat endoscopy. The specificity of the test for gastric cancer was 81.3%. Among those patients with false positive results who had endoscopic biopsy were four out of the five cases of severe dysplasia, and four out of the 13 cases of type 2B intestinal metaplasia. Atrophic gastritis alone or with intestinal metaplasia was found in 95.9% of the false positives who were biopsied.
Nitrogen Balance in the Ecosystem of the Cystic Fibrosis Lung
Authors: Nadzeya V. Marozkina, Benjamin Gaston
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Applying these observations from greatly reduced systems to the topic at hand leads to the prediction that putative strain injury thresholds must vary with flow, respiratory rate, and most importantly with end-expiratory lung volume.In fact, the classic experiments of Webb and Tierney, which underscored the lungprotective effects of PEEP, are entirely consistent with this prediction (14).Mechanical ventilation produced much less injury in anesthetized rats, when FRC was raised with PEEP, even though the lungs were inflated to similar end-inspiratory volumes.Lung-protective effects of PEEP (and consequently of increased FRC) are commonly attributed to prevention of so-called ''atelect-trauma'' resulting from injurious interfacial stresses (15, 16).However, given the effects of strain-amplitude on cell and tissue mechanics, it is quite possible that reductions in VT per se, irrespective of the average volume about which lungs are oscillated, account for lung protection ( 14).Hager and colleagues' post hoc analysis of ARMA data, which suggested benefit of low-tidal-volume ventilation across all Pplat quartiles, may be interpreted in that context (17).In summary, then, it seems inescapable that the risk of lung damage from mechanical ventilation, even when applied to healthy lungs, is multifactorial and cannot be linked to a single variable.As far as the strain-injury threshold is concerned it is conditional on PEEP and probably on flow and rate settings as well.This is not to distract from the conceptual advantage of quantifying lung deformation in terms of strain as opposed to VT normalized by predicted body weight (PBW), because strain accounts for disease-related unit loss (18).Protti and colleagues appropriately caution against the uncritical application of a porcine model-derived strain threshold to patient care, but their message is unmistakable: a normal lung can tolerate fairly large tidal volumes for fairly long periods of time!
Abstract P1-11-03: Pathological Complete Response after Neoadjuvant Chemotherapy + Trastuzumab Treatment Predicts Survival and Detects a Patient Subgroup at High Need for Improvement of Anti-HER2 Therapy. Three Year Median Follow-Up Data of the TECHNO Trial
Authors: M Untch, PA Fasching, GE Konecny, S Hasmueller, A Lebeau, R Kreienberg, O Camara, V Müller, A du Bois, T Kühn, E Stickeler, N Harbeck, C Höss, S Kahlert, T Beck, W Fett, K Mehta, G von Minckwitz, S. Loibl
Journal: Cancer Research (2010)

Abstract Purpose: To evaluate the efficacy and safety of epirubicin/cyclophosphamide followed by paclitaxel/trastuzumab as neoadjuvant treatment in patients with HER2-overexpressing primary breast cancer (BC). Patients and Methods: Patients with HER2-overexpressing primary BC (≥2cm or inflammatory BC) received preoperative 4 cycles epirubicin/cyclophosphamide (90/600 mg/m2), q3w) followed by 4 cycles paclitaxel 175 mg/m2 q3w with trastuzumab 6 mg/kg body weight q3w (8 mg/kg as loading dose) followed by surgery. Trastuzumab was continued after surgery until completion of 12 months treatment. The primary endpoint was pathological complete response (pCR) defined as no invasive tumor in the breast and axillary lymph nodes. Results: Two hundred seventeen patients were enrolled. 39% achieved a pCR. Breast conserving surgery was possible in 138/217 (64%) of the patients. Median follow-up was 41 months and 3-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (p=0.01). Three year overall survival (OS) was 96% in patients with pCR compared to 86% without pCR (p=0.025). In multivariate analysis pCR remained a significant prognostic factor for DFS and OS (DFS hazard ratio (HR) 2.5 [95% CI 1.2-5.1] p=0.013; OS HR 4.9 [95% CI 1.4-17.4] p=0.012). A cardiac event was reported in 8/217 (3.7%) patients; 6 had an LVEF decrease and two developed 2 (0.9%) clinical congestive heart failure. Conclusion: The neoadjuvant combination of trastuzumab and chemotherapy results in a high chance for a pCR. However, those patients without a pCR have an increased risk for relapse and death and are therefore candidates for further improvement of anti-HER2 directed therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-03.