tbuckley/cabot-search huggingface dataset:
P1 Clinical and economic benefit of cardiopulmonary exercise testing (CPX) in pulmonary hypertension
Authors: B. Mukherjee, D. Sirisena, K. Murphy, H. Tighe, L. Howard
Journal: Thorax (2011)

<h3>Rationale</h3> The exercise response in pulmonary hypertension (PH) has characteristic features, including decreased peak oxygen consumption, increased ventilatory inefficiency (VE/VCO2 slope) and widened alveolar-arterial gradient. These features can be used in diagnosing PH or distinguishing it from other causes of breathlessness. Many of the measurements from CPX are effort-independent, unlike the 6-min walk test, and can be used to discriminate uncontrolled PH from other factors which may affect peak capacity, such as obesity. We wished to evaluate the clinical and economic impact of CPX in PH. <h3>Methods</h3> We performed a retrospective analysis of 552 studies performed between August 2007 and August 2010. The impact of these tests was assessed by reviewing clinic letters and multidisciplinary team minutes. <h3>Results</h3> As a direct consequence of CPX, (1) 69 (13%) new non-PH diagnoses were made leading to changes in management and non-PH therapy in 18 (3%); (2) cardiac catheterisation was avoided in 69 (13%) and identified as necessary in 5 (1%), with a net saving of £179.5k; (3) 33 non-PH causes for patients9 symptoms were identified, preventing the addition of unnecessary and expensive therapies, saving £318.9k; 4) four patients were identified as needing additional therapy, albeit at greater cost (£26.6k); 5) finally, CPX facilitated confident discharge of patients in 38 (7%). The total saving using CPX over 3 years was £457.9k. Appropriate charging structures are not in place for CPX and testing was carried out using research facilities, however, a new national tariff for CPX is set at £235/test. This would still result in net saving of £328.2k (a <i>gain</i> of £594/test) in addition to the clinical benefit. We identified further savings of £93.6k which could have resulted from use of CPX earlier in the diagnostic process, increasing the net gain from £594 to £764 per test. <h3>Conclusion</h3> CPX provides clinical and financial benefit by directing investigations and treatments in a substantial number of cases. CPX prevented patients undergoing expensive and invasive investigations to establish diagnoses and monitor progression. CPX also improved appropriate use of therapies by characterising patients9 functional capacity and identifying when alternative conditions were responsible for patients9 deterioration.
Controlled trial of cromoglycate and slow-release aminophylline in perennial childhood asthma.
Authors: A T Edmunds, F Carswell, P Robinson, A O Hughes
Journal: BMJ (1980)

Even in the middle of an epidemic of a very serious illness, outbreaks of other infectious diseases will continue. Clinicians need to be able to make rapid decisions about the nature of the outbreak and how to manage it. A balance needs to be struck between managing all patients as if they have the worst-case scenario illness and the resultant risks to themselves, their colleagues and the mission. This paper reviews basic epidemiological tools that inform robust decision-making in the management of such outbreaks. It then describes how a pragmatic approach, combined with effective use of these techniques, rapid diagnostics and remote specialist support, allowed a large outbreak of gastroenteritis to be safely and effectively managed during the response to the Ebola virus disease epidemic in Sierra Leone.
Treatment of Narcotic-Depressed Respiration
Authors: IRWIN A. BUCHWALD
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 March 1973Treatment of Narcotic-Depressed RespirationIRWIN A. BUCHWALD, M.D.IRWIN A. BUCHWALD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-3-461_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his comprehensive review of drug-induced pulmonary disease, in the December 1972 issue (pp. 977-991), Dr. Rosenow implies that nalorphine hydrochloride is the opioid-narcotic antagonist of choice in the treatment of heroin-induced pulmonary edema. Recent literature (1), however, indicates that naloxone hydrochloride (Narcan®) may well be superior to nalorphine hydrochloride (Nalline®) in the emergency treatment of presumed narcotic-induced respiratory depression. The basis for this contention is the fact that nalorphine aggravates respiratory depression caused by non-opioid drugs such as barbiturates, cannabis, and cocaine; naloxone, on the other hand, will not aggravate non-opioid-induced respiratory depression. In emergency conditions...Reference1. Naloxone hydrochloride (Narcan). A new narcotic antagonist. Med Lett Drugs Ther 14:2-3, 1972 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pulmonary Unit Massachusetts General Hospital Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1973Volume 78, Issue 3Page: 461-461KeywordsCannabisCocaineDrugsEdemaPulmonary diseasesRespirationRespiratory system procedures Issue Published: 1 March 1973 PDF DownloadLoading ...
Abstract 2412: The modulatory effects of H. pylori infection in the DNA mismatch repair
Authors: Juliana C. Santos, Victor R. de Almeida, Wolfgang Fischer, Rainer Haas, Marcelo L. Ribeiro
Journal: Cancer Research (2014)

Abstract The bacterial pathogen H. pylori chronically infects the human gastric mucosa and is the leading risk factor for the development of gastric cancer. It is believed that during the infection the organism causes an impairment of DNA repair in the gastric epithelium. Thus, we evaluated the in vitro modulatory effects of H. pylori infection in the DNA mismatch repair (MMR). To evaluate the effects of H. pylori on MMR, AGS gastric carcinoma cell line and the H. pylori strain P12 were used in co-culture experiments for 4, 8 and 12 h. In addition, to analyze the potential effects of virulence factors on MMR, the ΔcagPAI, ΔvacA, ΔbabA, ΔhopQ, and Δtfs4 mutants were also subjected to co-culture experiments. The expression levels of EXO1, MLH1, MSH2, MSH3, MSH6, POLD3, PMS1, and PMS2 were assessed by real-time PCR. Moreover, expression levels of five previously screened miRNAs (miR-142-5p, miR-150-5p, miR-155-5p, miR-3163, and miR-4775), which are predicted to target MMR genes, were also evaluated by real-time PCR. Our data show that H. pylori infection significantly down-regulates the expression of all selected genes. Regarding the virulence factors, the results suggest that the modulation on gene expression might be dependent on cagPAI, vacA, and the type IV secretion (TFS4) system. Although the infection up-regulates miR-150-5p, miR-155-5p, miR-3163, and miR-4775, only the expression of miR-155-5p is related with virulence factors. Briefly, this study shows that H. pylori regulates the expression of several MMR genes, and it may be related with cagPAI, vacA, and the TFS4 system. Taking into account that MLH1, MSH2, and MSH6 are the miR-155-5p predicted targets, these preliminary data suggest that the observed virulence factor-dependent repression of miR expression could be responsible for the down-regulation of these MMR genes. Citation Format: Juliana C. Santos, Victor R. de Almeida, Wolfgang Fischer, Rainer Haas, Marcelo L. Ribeiro. The modulatory effects of H. pylori infection in the DNA mismatch repair. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2412. doi:10.1158/1538-7445.AM2014-2412
Distinct antibody specificities to a 64-kD islet cell antigen in type 1 diabetes as revealed by trypsin treatment.
Authors: M R Christie, G Vohra, P Champagne, D Daneman, T L Delovitch
Journal: The Journal of Experimental Medicine (1990)

Type 1 diabetes is associated with antibodies that immunoprecipitate a 64-kD islet cell membrane protein from detergent extracts of pancreatic islets. In this study we have determined whether mild trypsin treatment of islet membranes can release fragments of the antigen that bind antibodies in the serum of Type 1 diabetic patients. Partial tryptic proteolysis of [35S]methionine-labeled 64-kD antigen immunoprecipitated from detergent extracts of rat islets resulted in the formation of 50-, 40-, and 37-kD fragments. Similar sized fragments were recovered when sera from diabetic patients were employed to immunoprecipitate polypeptides solubilized by mild trypsin treatment of a particulate fraction of radiolabeled rat islets. Of 27 diabetic patients, 22 possessed antibodies to the 50-kD polypeptide and 21 to the 40- and 37-kD polypeptides. A positive association was found between 64k antibodies and antibodies to the 50-kD fragment but not between 64k antibodies and antibodies to the 40- or 37-kD fragments. Some 64k antibody negative patients possessed antibodies that efficiently immunoprecipitated the latter fragments. Serum from 25 of 27 (93%) diabetic patients immunoprecipitated at least one of the three tryptic polypeptides. One of 20 nondiabetic controls immunoprecipitated a 50-kD polypeptide and all controls were negative for antibodies to 40- and 37-kD fragments. Thus, Type 1 diabetes is associated with the presence of at least two antibody reactivities to distinct determinants of the 64-kD antigen, and some patients may possess antibodies to a cryptic epitope on the detergent-solubilized molecule. These data suggest that the detection of antibodies (present in 93% of patients) to epitopes on tryptic polypeptides of the 64-kD antigen may be of even greater diagnostic value for the onset of Type 1 diabetes than analyses of antibodies reactive with the intact 64-kD antigen.
Wiring the developing heart: a serious matter for adulthood
Authors: D. Franco
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Exploration of human, rat and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism’ by C. Danielsson et al ., pp. 23–32, this issue. 

The normal functioning of the heart resides in its coordinated and effective pumping capacity. Contraction of the heart is provided by the ordered and intricate design of the contractile apparatus, the sarcomere, while the coordination of contraction is accomplished by the cardiac conduction system.1 At the cellular level, the electrical properties of the contracting cardiomyocytes are governed by a complex array of inward and outward ion currents that configure the cardiac action potential. If we take as a paradigm the human cardiomyocyte, upstroke sodium current ( I Na) is responsible for depolarization of the cardiomyocyte plasma membrane,2 whereas a variety of outward potassium currents ( I Kur, I Kr, I Ks, I K1, I TO) provide the means to repolarize the cell membrane as well as to keep constant the resting membrane potential.3,4 Electrical coupling—that is to say from conduction to contraction—is provided mainly by calcium currents ( I Ca).5

It is important to acknowledge the nature of the regulation of the cardiac action potential, since limited variability is observed within the sodium currents in atrial and ventricular cardiomyocytes, a situation that similarly applies to the electrical coupling governed by calcium currents. However, a large variability is observed for the repolarization and resting membrane potential.6,7 For example, distinct resting membrane potential and cardiac action potential morphologies are observed for atrial and ventricular myocytes, and even within ventricular …
Immunization of Preschool Children with Oral Poliovirus Vaccine (Sabin)
Authors: D. M. Horstmann
Journal: JAMA (1961)

The effectiveness of an oral polivirus vaccine using Sabin strains was studied among some 350 preschool children beginning in January, 1960. Although 79% of the children had previously received 3 or more doses of killed virus vaccine, a relatively high per cent lacked antibody to one or more types, and 22% of 348 children were triple negatives. The oral vaccine was given according to 3 different dosage schedules: each type singly; Type 1 followed by Types 2 and 3 together; and trivalent vaccine twice, 6 weeks apart. The infection and antibody conversion rates were similarly high for all 3 schedules, the overall conversion rates being 95% for Type 1, 98% for Type 2, and 86% for Type 3. The results emphasize the desirability of oral vaccine for young preschool children regardless of previous administration of multiple doses of killed Salk-type vaccine.
Long‐term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate‐to‐severe psoriasis: results from the PHOENIX 2 study through 5 years of follow‐up
Authors: R.G. Langley, M. Lebwohl, G.G. Krueger, P.O. Szapary, Y. Wasfi, D. Chan, M.C. Hsu, Y. You, Y. Poulin, N. Korman, J.C. Prinz, K. Reich
Journal: British Journal of Dermatology (2014)

Evaluation of the dosing flexibility and long-term efficacy of biological agents is limited.To evaluate the long-term efficacy and safety of ustekinumab with and without dosing adjustment in the 5-year PHOENIX 2 study.Patients were randomized to placebo or ustekinumab (45 or 90 mg) at weeks 0, 4, then every 12 weeks; patients receiving placebo crossed-over at week 12. Dosing adjustments were permitted at/beyond week 28 for early adjusters (weeks 28 or 40 per response); late adjusters (during long-term extension per investigator judgement); and nonadjusters (maintained randomized treatment throughout the study). Efficacy and safety were evaluated through weeks 244 and 264, respectively.In the overall population, 70% (849 of 1212) of ustekinumab-treated patients completed treatment through week 244, with high proportions of patients responding to the 45-mg and 90-mg doses, respectively: 75% improvement in Psoriasis Area and Severity Index (PASI 75) (76·5% and 78·6%) and PASI 90 (50·0% and 55·5%). Approximately 20% of patients were early adjusters, 30% were late adjusters and 50% were nonadjusters. Approximately half of the late adjusters initiated adjustments after already achieving PASI 75. Improved response was generally observed following dosing adjustments. Through week 264, safety event rates did not increase and event rates were generally comparable between dose groups and between patients with and without dosing adjustment.Treatment with ustekinumab for up to 5 years was safe and effective. Improved response was generally demonstrated following dosing adjustments; further investigations are required to quantify actual incremental benefits. The results also suggest that some patients may desire treatment goals beyond PASI 75.
The Cause of the Wavy or Interrupted Breath-Sound of Incipient Phthisis
Authors: D. C. McVail
Journal: BMJ (1883)

the blood-glands was traced to William Hewson (1739-1774), who was the first to show that the so-called blood-glands were concerned in &ne function, namely, in the elaboration, or, as he called it, the "secretion" of blood.For many years Hewson's worlk h*d no at-
The Learning Curve-Reply
Authors: Martin J. Hatlie
Journal: JAMA (1994)

In Reply.  —The letters from Drs Matz and Sibert underscore the importance of reevaluating both credentialing procedures and the certification of postgraduate training programs to ensure that financial incentives to advance implementation of new technologies do not override the more fundamental concern for patient safety. These are not simple tasks, and to the extent they challenge medical staffs or professional organizations to approach their professional oversight responsibilities more stringently or in a faster time frame, they will undoubtedly cause anxiety. But the failure to establish patient safety as the litmus test—even when patients themselves are demanding the latest unproven treatment options— has a huge downside risk. In addition to increased exposure to a malpractice claim, patients become less trusting of the profession over the long run, and payers find more justification to encroach—whenever it is in their self-interest—on the physician's unique role in determining what constitutes appropriate care. Dr Caropreso
REACTIVATION IN VITRO OF IMMUNOCOMPETENCE IN IRRADIATED MOUSE SPLEEN
Authors: Amiela Globerson, Robert Auerbach
Journal: The Journal of Experimental Medicine (1967)

The restoration of immunological competence to irradiated adult mouse spleen was studied using an in vitro assay system. Competence of the spleen to evoke a graft versus host reaction in vitro was lost upon sublethal irradiation (550 R). Regeneration of immune competence occurred when such spleens were grown for 2-3 days in the presence of thymus tissue, but not when grown in the presence of a variety of other tissues. This thymic activity was demonstrated to occur across an intervening Millipore filter barrier. When lethal doses of irradiation were used, reactivation of immune competence did not occur unless both thymus and bone marrow were present. In this experimental situation the bone marrow appeared to supply the immunocompetent cells.
Thrombocytopenia in Acute Infections
Authors: H. A. Reimann
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Since 1964 several authors have described thrombocytopenia, occasionally with purpura, during viral infections as if it were a new observation.<sup>1-3</sup>These reports prompted two letters (<b>190</b>:945, 1964;<b>196</b>:460, 1966) citing references to prior studies showing the same events. Thrombocytopenia during acute infections in general, followed by transient thrombocytosis, was noted first by Hayem 86 years ago and confirmed many times since then. References to pertinent papers about many viral, rickettsial, bacillary, coccal, and other infections can be found in Tocantin's review.<sup>4</sup> The editorial (<b>205</b>:105, 1968) comments on two new publications about Rocky Mountain spotted fever. The occurrence of thrombocytopenia is not surprising, but its degree, as in other hemorrhagic infections, may be unusual and is dependent on the nature of the lesions. It is regarded better as an integral feature of the disease rather than a complication of it. Speculation that "thrombocytopenia
Eosinophil chemotactic factor in tumour tissue from a patient with Kimura's disease
Authors: M. ISODA
Journal: British Journal of Dermatology (1988)

An extract of tumour tissue from a patient with Kimura's disease was tested for eosinophil chemotactic activity using the Boyden chamber method. Eosinophil chemotactic activity was detected in the tissue extract, and after gel filtration maximum activity was found in the fraction with a molecular weight of approximately 1000 daltons. This factor may play a role in the tissue eosinophilia which occurs in Kimura's disease. Kimura's disease is characterized clinically by marked eosinophilia in the peripheral blood and asymptomatic subcutaneous tumours, and his'tologkally by follicular aggregations of lympho cytes with well‐developed germinal centres, and marked eosinophilic infiltration. The disease is rare, being seen only in Orientals. Subcutaneous angiolymphoid hyperplasia with eosinophilia (ALHE), reported in the West,1 has been used synonymously with Kimura's disease,2–5 However, its relationship to Kimura's disease is still controversial.6,7 Tissue eosinophilia in this disease is thought to be the result of an IgE mediated immune response, because of elevated serum IgE levels, infiltration of eosinophils and mast cells into the tumours, and detection of IgE in the lymphoid follicles on immunofluorescence.8 However, there are no reports to our knowledge about eosinophil chemotactic activity in the tissue. The present study was undertaken to examine the eosinophil chemotactic activity of tissue from a typical case of Kimura's disease.
The Origin of the Term Neurocirculatory Asthenia
Authors: Samuel A. Levine
Journal: New England Journal of Medicine (1965)

ON reading the letter by Dr. Calvin P. Leeman in the April 23, 1965, issue of the Journal I was struck by the thought that few physicians would know the origin of the term neurocirculatory asthenia, — how, where and when it was first used. Since I may be the only living person who might know, it appears appropriate to record the actual facts.During the early months of American participation in World War I a small group of young American medical officers were attached to the British Medical Corps, working at the British Heart Hospital in Colchester, England. This . . .
Frigyes and Sandor Korányi
Authors: Gy. Regöly-MÉrei
Journal: JAMA (1969)

<h3>To the Editor:—</h3> As a research worker in the history of Hungarian medicine, I would like to add to your brief biography of the Korányi's (<b>204</b>:252, 1968). Frigyes Korányi, 1827-1913, laid foundation of the study of internal medicine in 19th century Hungary. He was the professor of internal medicine at the University Medical School of Budapest. His interests included splenomegalies, the pathology of valvular disease, diagnosis of cerebral tumors, the pathology and therapy of contagious diseases, and especially the treatment of tuberculosis. He was one of the first to describe the triangular dullness in pleuritis, the "Korányi-Rauchfuss-Grocco's triangle." His son, Sándor (1866-1944), was later professor at the same university. He was a pathfinder in the application of physical and chemical methods in medicine and, with G. Richter, wrote a book on this subject in German in 1908. He studied the activity of the normal and pathological kidney in the last
Low zero-flow pressure and minimal capacitance effect on diastolic coronary arterial pressure-flow relationships during maximum vasodilation in swine.
Authors: G A Pantely, H D Ladley, J D Bristow
Journal: Circulation (1984)

During maximum dilation with adenosine in dogs, the diastolic coronary pressure at which flow ceases (Pzf) has been observed to be up to 27 mm Hg above coronary sinus and right atrial pressures. We studied swine to measure the Pzf and to determine the effects of interventions that change collateral flow and coronary capacitance. In 44 swine, the left anterior descending coronary artery (LAD) was instrumented with two catheters, a hydraulic occluder, and a flowmeter. Late diastolic and mean pressure-flow relationships were constructed at a series of pressures produced by partial LAD occlusions during maximum vasodilation. The late diastolic Pzf was 7.0 +/- 2.2 mm Hg (mean +/- SD), less than 4 mm Hg above right atrial pressure; the mean Pzf was 12.1 +/- 3.1 mm Hg, less than 9 mm Hg above right atrial pressure. The Pzf in the LAD did not change significantly (1) during transient simultaneous occlusion of the right coronary artery (RCA) in seven swine (late diastolic Pzf with the RCA open was 6.6 +/- 1.5 mm Hg and with the RCA closed it was 6.0 +/- 1.5 mm Hg), (2) during increased left ventricular systolic pressure (LVSP) in seven swine (late diastolic Pzf with LVSP of 123 mm Hg was 5.5 +/- 2.2 mm Hg and with LVSP of 184 mm Hg it was 7.3 +/- 2.8 mm Hg), or (3) during increased heart rate in eight swine (late diastolic Pzf at heart rate of 107 per minute was 10.8 +/- 2.9 mm Hg and at 180 per minute it was 12.7 +/- 2.1 mm Hg). Similar results were obtained from analysis of the mean pressure and flow data. The Pzf in the LAD of swine is very close to right atrial pressure, and it did not change significantly during interventions that would modify collateral flow (reduced by RCA occlusion and enhanced by increased LVSP) and coronary capacitance (increased LVSP and increased heart rate). This low Pzf is beneficial in maintaining flow at lower coronary arterial perfusion pressures.