tbuckley/cabot-search huggingface dataset:
Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites
Authors: Alyse N Douglass, Heather S Kain, Marian Abdullahi, Nadia Arang, Laura S Austin, Sebastian A Mikolajczak, Zachary P Billman, Jen C C Hume, Sean C Murphy, Stefan H I Kappe, Alexis Kaushansky
Journal: Molecular Therapy (2015)

Eliminating malaria parasites during the asymptomatic but obligate liver stages (LSs) of infection would stop disease and subsequent transmission. Unfortunately, only a single licensed drug that targets all LSs, Primaquine, is available. Targeting host proteins might significantly expand the repertoire of prophylactic drugs against malaria. Here, we demonstrate that both Bcl-2 inhibitors and P53 agonists dramatically reduce LS burden in a mouse malaria model in vitro and in vivo by altering the activity of key hepatocyte factors on which the parasite relies. Bcl-2 inhibitors act primarily by inducing apoptosis in infected hepatocytes, whereas P53 agonists eliminate parasites in an apoptosis-independent fashion. In combination, Bcl-2 inhibitors and P53 agonists act synergistically to delay, and in some cases completely prevent, the onset of blood stage disease. Both families of drugs are highly effective at doses that do not cause substantial hepatocyte cell death in vitro or liver damage in vivo. P53 agonists and Bcl-2 inhibitors were also effective when administered to humanized mice infected with Plasmodium falciparum. Our data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a new avenue to prevent malaria. Eliminating malaria parasites during the asymptomatic but obligate liver stages (LSs) of infection would stop disease and subsequent transmission. Unfortunately, only a single licensed drug that targets all LSs, Primaquine, is available. Targeting host proteins might significantly expand the repertoire of prophylactic drugs against malaria. Here, we demonstrate that both Bcl-2 inhibitors and P53 agonists dramatically reduce LS burden in a mouse malaria model in vitro and in vivo by altering the activity of key hepatocyte factors on which the parasite relies. Bcl-2 inhibitors act primarily by inducing apoptosis in infected hepatocytes, whereas P53 agonists eliminate parasites in an apoptosis-independent fashion. In combination, Bcl-2 inhibitors and P53 agonists act synergistically to delay, and in some cases completely prevent, the onset of blood stage disease. Both families of drugs are highly effective at doses that do not cause substantial hepatocyte cell death in vitro or liver damage in vivo. P53 agonists and Bcl-2 inhibitors were also effective when administered to humanized mice infected with Plasmodium falciparum. Our data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a new avenue to prevent malaria.
Clinical Evaluation of Low-Dose Intradermally Administered Hepatitis B Virus Vaccine
Authors: Robert R. Redfield
Journal: JAMA (1985)

High cost and limited availability of the current hepatitis B virus vaccine lead to underutilization. To address this problem, we performed a vaccine trial comparing the currently recommended regimen of 20 micrograms of hepatitis B surface antigen (HBsAg) intramuscularly on days 0, 30, and 180, with a more economical regimen of 2 micrograms of HBsAg intradermally on days 0, 30, and 180. This trial was performed in 50 seronegative health care workers to assess the immunogenicity and local reactogenicity of both vaccine regimens. We found no significant difference in seroconversion between the intradermal group (96%) and the intramuscular group (100%). Mean ratios of test sample value to mean negative control value for antibody to HBsAg at 360 days were not significantly different (intradermal group, 84 +/- 26; intramuscular group, 120 +/- 22). Reactions in both groups were minor. Although the optimal dose of HBsAg was not investigated, our data demonstrate that 0.1 mL of inactivated hepatitis B virus vaccine (Heptavax-B) intradermally is immunogenic in healthy adults. Vaccination by this regimen can broaden hepatitis B virus disease prevention.
Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders
Authors: Zhaohui Ye, Huichun Zhan, Prashant Mali, Sarah Dowey, Donna M. Williams, Yoon-Young Jang, Chi V. Dang, Jerry L. Spivak, Alison R. Moliterno, Linzhao Cheng
Journal: Blood (2009)
Prevention of Aneurysm Development and Rupture by Local Overexpression of Plasminogen Activator Inhibitor-1
Authors: Eric Allaire, David Hasenstab, Richard D. Kenagy, Barry Starcher, Monika M. Clowes, Alexander W. Clowes
Journal: Circulation (1998)

Background —Arterial aneurysms exhibit a loss of elastin and an increase in the plasminogen activators urokinase plasminogen activator (u-PA) and tissue plasminogen activator (t-PA). Because u-PA, t-PA, and plasmin have a limited proteolytic activity against elastin, the role of plasminogen activators in the aneurysmal disease is unclear. To investigate this question, we overexpressed plasminogen activator inhibitor-1 (PAI-1), an inhibitor of t-PA and u-PA, in a rat model of aortic aneurysm. Methods and Results —Guinea pig–to-rat aortic xenografts were seeded with syngeneic Fischer 344 rat smooth muscle cells retrovirally transduced with the rat PAI-1 gene (LPSN group) or the vector alone (LXSN group). Some grafts were not seeded with cells (NO group). Western blots showed increased PAI-1 in grafts from the LPSN group compared with LXSN and NO groups. All grafts in the NO group (n=8) and 40% in the LXSN group ruptured between days 4 and 14. At 4 weeks in the LXSN group, the remaining unruptured grafts (n=6) were aneurysmal (diameter increase ≥100%), whereas in the LPSN group (n=6) none of the grafts had ruptured or were aneurysmal. Elastin was preserved in the LPSN group. t-PA, the major PA expressed in the model, was decreased in the LPSN group compared with the other groups, as determined by zymography. Quantitative zymography showed decreased levels of two matrix metalloproteinases (MMPs), a 28-kD caseinase, and activated MMP-9 in the LPSN group. Conclusions —The blockade of plasminogen activators prevents formation of aneurysms and arterial rupture by inhibiting MMP activation.
Postpartum eclampsia of late onset: a complicated case
Authors: Kirsten Duckitt
Journal: BMJ (2005)

Adjuvant trastuzumab for breast cancer Assessing HER2/neu status incurs more costs for treatmentEditor-The results of recent trials are likely to continue to fuel the demand for trastuzumab in the adjuvant setting of early breast cancer, 1 as well as a possible neoadjuvant treatment in the near future.However, Dent and Clemons did not discuss the difficulty in obtaining accurate and reproducible assessment of HER2/neu gene overexpression.Immunohistochemical testing measures HER2/neu protein expression whereas in situ hybridisation measures gene amplification.Patients with equivocal immunohistochemical results require in situ hybridisation to determine definitive status because interobserver variability using immunohistochemical testing is appreciable.At least 20% of patients with positive immunohistochemical results will be truly negative for HER2/neu gene amplification; these patients would not benefit from trastuzumab. 2 These difficulties in assessing HER2/ neu status have been encountered in studies testing trastuzumab, and in situ hybridisation testing has been used as the gold standard. 3 As the clinical utility of trastuzumab widens guidelines on HER2/neu testing must be clear to ensure appropriate use of trastuzumab.Clearly this testing will incur additional costs to trastuzumab treatment.
Prognostic Value of Echocardiography in Normotensive Patients With Acute Pulmonary Embolism
Authors: Piotr Pruszczyk, Sylwia Goliszek, Barbara Lichodziejewska, Maciej Kostrubiec, Michał Ciurzyński, Katarzyna Kurnicka, Olga Dzikowska-Diduch, Piotr Palczewski, Anna Wyzgal
Journal: JACC. Cardiovascular imaging (2014)
Variation in Serum Gastrin Levels in Zollinger-Ellison Syndrome.
Authors: Robert J. Kucera
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Variation in Serum Gastrin Levels in Zollinger-Ellison Syndrome.Robert J. Kucera, M.S., Martin G. Durkin, M.D.Robert J. Kucera, M.S.Search for more papers by this author, Martin G. Durkin, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-860_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIncreased gastric acid output and elevation of serum gastrin levels are characteristic features of the Zollinger-Ellison syndrome. Variation in acid output in this disorder is well known; recently we have observed marked spontaneous variation in serum gastrin levels. In our patient the serum gastrin concentration ranged from 400 to 13 000 pg/ml.To further evaluate possible mechanisms that might control gastrin release in this disorder and thus permit differentiation from the normal, the effects of antral acidification, prolonged intragastric infusion of antacid, the response to feeding, insulin-induced hypoglycemia, and secretin administration were studied. Serum gastrin levels were measured by radioimmunoassay.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Columbia, Mo. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOrganic electrosyntheses in industry 1 May 1972Volume 76, Issue 5Page: 860-860KeywordsAttentionGastrinHypoglycemiaInsulin secretionRadioimmunoassaysSecretinZollinger Ellison syndrome Issue Published: 1 May 1972 PDF downloadLoading ...
Plexiform schwannoma mimicking haemangioma: pitfalls in clinical diagnosis and histological interpretation
Authors: S. Lo, P. How, A.L.M. Moss
Journal: British Journal of Dermatology (2007)

Journal Article Plexiform schwannoma mimicking haemangioma: pitfalls in clinical diagnosis and histological interpretation Get access S. Lo, S. Lo Department of Plastic Surgery, St George’s Hospital, London SW17 0QT, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. How, P. How Department of Plastic Surgery, St George’s Hospital, London SW17 0QT, U.K. Correspondence: Peter How. E‐mail: pd_how@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar A.L.M. Moss A.L.M. Moss Department of Plastic Surgery, St George’s Hospital, London SW17 0QT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 4, 1 October 2007, Pages 838–839, https://doi.org/10.1111/j.1365-2133.2007.08128.x Published: 01 October 2007
Morbidity and healthcare utilisation of children in households with one adult: comparative observational study
Authors: D M Fleming, J R H Charlton
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To identify and consider differences in morbidity in children in households with one adult presenting to general practitioners compared with children in households with more than one adult. <b>Design:</b> Observational study; data analysed with logistic regression controlling for age, sex, and practice. <b>Subjects:</b> 93 356 children aged 0–15 years included in the fourth national study of morbidity in general practice and for whom data about household structure were available. Among them 10 983 (11.8%) were living in households with a sole adult. <b>Methods:</b> Morbidity data were recorded from each consultation as the assessment diagnosis made by the general practitioner. <b>Main outcome measures:</b> Number of consultations and consultations per person for any illness, infections, acute respiratory infections, asthma, and accidents; number presenting and mean consultations per person for immunisation; number receiving home visits and home visits per person visited; average annual frequency of consultation among those consulting. <b>Results:</b> Compared with children in other households, a higher proportion of children in households with one adult consulted for infections and accidents. The proportion consulting for immunisation was lower and the proportion receiving home visits greater. Mean numbers of consultations per person consulting were also generally higher for all conditions. For infections, accidents, and home visits, the differences were evident in all age groups. <b>Conclusions:</b> The study confirms the importance of single parent families as an indicator of deprivation. Children in such families should be targeted for immunisation and accident prevention. <h3>Key messages</h3> Children in households with one adult consult general practitioners more frequently than those in households with two or more adults and receive increased numbers of home visits They are more likely to consult for accidents, and they attend less frequently for immunisation Single parent households are an appropriate indicator of deprivation Children from households with one adult require specific targeting by general practitioners, health visitors, and primary healthcare workers for accident prevention and immunisation uptake
A Phase I Study of AZD9291 in Patients with Egfr-Tki-Resistant Advanced Nsclc – Updated Progression Free Survival and Duration of Response Data
Authors: P.A. Jänne, M.-J. Ahn, D.-W. Kim, S.-W. Kim, D. Planchard, S.S. Ramalingam, P. Frewer, M. Cantarini, S. Ghiorghiu, J.C.-H. Yang
Journal: Annals of Oncology (2015)
Cost-Effectiveness of Dual-Chamber Pacing Compared With Ventricular Pacing for Sinus Node Dysfunction
Authors: Stéphane Rinfret, David J. Cohen, Gervasio A. Lamas, Kirsten E. Fleischmann, Milton C. Weinstein, John Orav, Eleanor Schron, Kerry L. Lee, Lee Goldman
Journal: Circulation (2005)

Compared with single-chamber ventricular pacing, dual-chamber pacing can reduce adverse events and, as a result, improve quality of life in patients paced for sick sinus syndrome. It is not clear, however, how these benefits compare with the increased cost of dual-chamber pacemakers.We used 4-year data from a 2010-patient, randomized trial to estimate the incremental cost-effectiveness of dual-chamber pacing compared with ventricular pacing and then projected these findings over the patients' lifetimes by using a Markov model that was calibrated to the first 5 years of in-trial data. To assess the stability of the findings, we performed 1000 bootstrap analyses and multiple sensitivity analyses. During the first 4 years of the trial, dual-chamber pacemakers increased quality-adjusted life expectancy by 0.013 year per subject at an incremental cost-effectiveness ratio of 53,000 dollars per quality-adjusted year of life gained. Over a lifetime, dual-chamber pacing was projected to increase quality-adjusted life expectancy by 0.14 year with an incremental cost-effectiveness ratio of approximately 6800 dollars per quality-adjusted year of life gained. In bootstrap analyses, dual-chamber pacing was cost-effective in 91.9% of simulations at a threshold of 50,000 dollars per quality-adjusted year of life and in 93.2% of simulations at a threshold of 100,000 dollars. Its cost-effectiveness ratio was also below this threshold in numerous sensitivity analyses that varied key estimates.For patients with sick sinus syndrome requiring pacing, dual-chamber pacing increases quality-adjusted life expectancy at a cost that is generally considered acceptable.
Use of combined diet and colestipol in long-term (7--7 1/2 years) treatment of patients with type II hyperlipoproteinemia.
Authors: P T Kuo, K Hayase, J B Kostis, A E Moreyra
Journal: Circulation (1979)

Long-term effects of diet and colestipol (a bile acid sequestrant) were studied in 25 patients with familial type II hyperlipoproteinemia. Serum lipids and body weights of an initial group of 30 patients were stabilized by low cholesterol-saturated fat-refined carbohydrate diet and the patients were then randomized into placebo and drug-treatment groups. After explaining that the drug is nontoxic and effective in lowering serum lipids, total cholesterol (C) and low-density lipoprotein cholesterol (LDL-C), colestipol (30 g/day) and diet were given to the 25 patients who remained in the long-term follow-up program. The treatment resulted in highly significant lowering of serum lipids (mg/dl, mean +/- SEM): C and LDL-C from 412.7 +/- 24.4 and 331.1 +/- 22.8 to 270 +/- 11.0 and 188.1 +/- 13.8, respectively (p less than 0.001 in each instance) over 7--7 1/2 years. Although we observed no absolute increase in high density lipoprotein (HDL), the HDL/LDL ratio was elevated. Long-term colestipol and diet treatment reduced the xanthoma size and stabilized serially angiographically visualized atherosclerotic lesions in 21 of the 25 patients who showed a satisfactory hypolipemic response. It did not cause nutritional or metabolic disturbances.
Comparison Between Magnifying Endoscopy and Histological, Culture and Urease Test Findings from the Gastric Mucosa of the Corpus
Authors: K. Yagi, A. Nakamura, A. Sekine
Journal: Endoscopy (2002)

Background and Study Aims: The incidence of Helicobacter pylori infection in Japan is high. Unlike the case in Western countries, H. pylori-induced gastritis in Japanese patients has a tendency to spread to the corpus. H. pylori-induced gastritis is characterized by a number of specific endoscopic findings. In a previous study, the endoscopic features and a magnified view of the gastric mucosa of the corpus of H. pylori-negative normal stomach were described. This report describes the specific histological features and magnified views of the H. pylori-negative stomach and compares them with those seen during H. pylori-induced gastritis. Patients and Methods: The anterior wall or greater curvature of the middle body of the stomachs of 297 patients were observed by magnifying endoscopy (× 80). Forceps biopsy was performed at the following locations: i) the magnified site, for histological examination; ii) the antral mucosa, for culture/urease test, and histology; and iii) greater curvature of the upper body for culture/urease test. Results: 72 patients were diagnosed as having H. pylori-negative normal stomach and 225 as having H. pylori-positive gastritis. The magnified views were classified into four types: i) collecting venules, with true capillaries forming a network, and gastric pits resembling pinholes (type Z-0; n = 80); ii) irregular true capillaries but no collecting venules observed (type Z-1; n = 36); iii) white gastric pits and sulci, with neither collecting venules nor true capillaries being seen (Z-2; n = 110); and iv) dilated pits with surrounding redness (Z-3; n = 71). All cases of H. pylori-negative normal stomach were type Z-0, whereas H. pylori-induced gastritis was present in all cases where the classification was Z-1, Z-2, or Z-3. Type Z-0 differed significantly from types Z-1, Z-2, and Z-3 with regard to the grade of inflammation, activity, and presence of H. pylori. Conclusions: Collecting venules and true capillaries forming a network with gastric pits in the center (type Z-0) were observed in the H. pylori-negative normal mucosa. The magnified views of H. pylori-related gastritis clearly differed from type Z-0.
Neonatal Bowel Obstruction With Unilateral Labial Swelling
Authors: Tafadzwa P. Makarawo, Jessica Bartock, Marc L. Cullen
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Polycythemia Associated with Uterine Fibroma
Authors: Allison R. Vanden Berg
Journal: JAMA (1963)

Erythrocytosis has been observed to occur infrequently in association with large uterine fibroids. Study of this case revealed erythrocytosis prior to surgery and a remission was noted after hysterectomy. It has been suggested that large intraabdominal tumors may interfere with normal pulmonary ventilation with resultant hypoxia which acts as a stimulus to erythropoietin production. An attempt to demonstrate elevated erythropoietin levels in this patient's unconcentrated serum and tumor extracts was unsuccessful. The failure to demonstrate increased erythropoietin activity in this case does not preclude the participation of this humoral mechanism.
Male-to-Female Transmission of HIV
Authors: Doug Trotter
Journal: JAMA (1987)

To the Editor.—  I was concerned about the nonchalant and confusing discussion of some troubling findings in the study of Padian et al. 1   Although absolutely no data are presented, several statements are made regarding  use and a lack of evident protection from infection with human immunodeficiency virus (HIV). A statement in the abstract, indicating that  use was not associated with infection, seems to contradict a statement later in the article indicating that condom use was not significantly associated with protection from infection. Confusingly, a later statement indicates that failure to use condoms was not significantly associated with infection. The findings hinted at in the statements are extremely troubling, since the use of condoms is being championed as the primary means of achieving safe sex in our sexually liberated society.  Since no data are presented, it is difficult to draw one's own conclusions. However, the clear implication from
What hospital work is really like
Authors: J. West, J. Straw
Journal: BMJ (1998)

Many medical school applicants may be attracted by the money, status, employment, variety, and job satisfaction in a medical career. But are these medical applicants making an informed career decision?

A hospital experience course has been started at the Derbyshire Royal Infirmary NHS Trust initiated by the postgraduate clinical tutor who saw the need for prospective medical students to be given a realistic idea of the implications of studying medicine.

In 1994 Grainger surveyed 735 preregistration house officers.1 A postal questionnaire assessed biographical and lifestyle data, career influences, regrets, and intentions. There was a section on careers advice. Half the respondents had received careers advice before they went to medical school. Before applying to medical school nearly all were aware of the length of undergraduate training, but only 54% were aware of the length of postgraduate training, while 35% were aware of hours of work. Thirty seven per cent had spent time with a general practitioner or a consultant and only 6% with a junior house officer before applying to medical school.

It was recommended that schools' careers advice should be better tailored to the needs of potential medical students. In particular:

Allen studied cohorts of medical qualifiers.2 They were randomly selected from each of the medical schools in Britain for the years 1966, 1976, and 1981. A parallel study followed up those cohorts and added …