tbuckley/cabot-search huggingface dataset:
The Plague Makers: How We Are Creating Catastrophic New Epidemics—And What We Must Do to Avert Them
Authors: Stuart M. Polly
Journal: JAMA (1995)

Does the title suggest a headline you might see while waiting to check out at the supermarket? Read on: Shocking in its revelations, alarming in its implications and overwhelmingly convincing in the evidence it offers,<i>The Plague Makers</i>warns that we are facing impending disaster. Pneumonia, rheumatic fever, meningitis, osteomyelitis, and countless other serious infectious diseases previously considered under control have suddenly reemerged and may soon reach epidemic proportions, plunging the world into a plague of misery and death unlike anything seen in over a half a century. So reads the dust cover for this book by Jeffrey A. Fisher, MD. Sensational, heady stuff! Designed to sell books, this yellow journalistic approach permeates the entire work, burying a real and serious issue under a pile of exaggeration, accusation, and sophistry. <i>The Plague Makers</i>attempts to associate the widespread and "indiscriminate" use of antibiotics with impending doom. Dr Fisher predicts "catastrophic
SPECIFIC AND EXTREME HYPERLEUKOCYTOSIS FOLLOWING THE INJECTION OF BACILLUS TYPHOSUS IN IMMUNIZED RABBITS
Authors: FREDERICK P. GAY
Journal: JAMA (1913)

epidermis, marked increase in the depth of the papillae and abundant, pigmentation ir the deeper portions of the corium where many chromatophores have wandered into the deeper strata.The cutaneous lesions arc identical with the inicio
Polymers Help Guide Cancer Drugs to Tumor Targets -- and Keep Them There
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Polymers Help Guide Cancer Drugs to Tumor Targets — and Keep Them There Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 21, 1 November 1995, Pages 1582–1584, https://doi.org/10.1093/jnci/87.21.1582 Published: 01 November 1995
Phase II Trial of Paclitaxel and Cisplatin in Patients with Extensive Stage Small Cell Lung Cancer: Cancer and Leukemia Group B Trial 9430
Authors: Thomas E. Stinchcombe, Ann M. Mauer, Lydia D. Hodgson, James E. Herndon, Thomas J. Lynch, Mark R. Green, Everett E. Vokes
Journal: Journal of Thoracic Oncology (2008)
Two Cases of Congenital Methaemoglobinaemia
Authors: C. P. Newcombe, J. Dawson
Journal: BMJ (1958)

Two Cases of Congenital MethaemoglobinaemiaCongenital methaemoglobinaemia is a rare condition, with frequently a strong familial incidence.It is associated with a normal or mildly polycythaemic red-cell count, and symptoms are mild or absent.In these respects it differs from the chronic secondary type which may accompany the prolonged use of drugs, and which is usually associated with chronic anaemia or granulocytopenia or both, and with considerable symptoms.Now that cyanotic congenital heart disease is often amenable to surgery the diagnosis of congenital methaemoglobinaemia is no longer academic, and, further, drug therapy can restore the appearance to normal.Two cases of congenital metbaemoglobinaemia are re- ported in which cyanotic congenital heart disease was at first suspected.CASE 1A man of 56, weighing 154 lb.(70 kg.), had been cyanosed from birth.He had always felt tired, and was intolerant of cold weather.Of nervous disposition, there had been lifelong frequency of micturition, with slight incontinence.He had always been constipated, and had had chronic bronchitis for a number of years.His parents were not cyanosed, and his only brother died aged 3 years (cause of death unknown).The patient had marked central cyanosis, no clubbing, B.P. 230/120, the heart was clinically normal, and there was moderate emphysema.Investigations.-Fluoroscopy showed slight left ventricular enlargement.Electrocardiogram was normal.Blood count: Hb 120% (17.8 g. /100 ml.); red cells, 5,900.000;P.C.V., 52.5%; M.C.H.C., 33.8 g./100 ml.; M.C.V., 88.9 cubic microns; M.C.H., 30.0 a/qg.Circulation time: left arm-lung 11.4 seconds (normal 3-8 seconds); right arm-lung, 11.5 seconds).right arm-tongue, 16.5 seconds (normal 9-18 seconds).Angiocardiography-performed from the left long saphenous vein, as anomalous drainage of the inferior vena cava was suspected-was normal.Spectroscopy showed no abnormal pigment.Arterial blood: pH 7.43; C02, 47.9 ml./100 ml., oxygen capacity, 16.83 ml./100 ml.=-Hb, 12.6 g./100 ml.Oxygen content, 15.39 ml./100 ml.Satura- tion, 91.5%.Methaemoglobin = 17.8 12.6 = 5.2 g./100
Aspirin Tolerance Induced in Aspirin‐Sensitive Asthmatics
Authors: M. L. Kowalski, I. Grzelewska‐Rzymowska, J. Rozniecki, M. Szmidi
Journal: Allergy (1984)

Twenty‐nine patients with asthma and aspirin‐sensitivity were studied in an attempt to induce tolerance to aspirin (ASA). Starting with the smallest ASA doses eliciting bronchial obstruction (threshold doses) we doubled the doses on subsequent days and finally achieved good tolerance of 600 mg ASA per day in 27 patients. It was more difficult to achieve tolerance in patients with low ASA‐thresholds than in patients with high ones. Daily ASA administration led to prolongation of the refractory state but when the intervals between consecutive doses were increased aspirm hypersensitivity recurred. The pause sufficient for a recurrence of sensitivity to ASA was measured in 16 patients and ranged from 24 h to 9 days Twelve patients challenged with indomethauen after ASA‐desensitisation showed good drug tolerance.
Reduction in extrathyroidal triiodothyronine production by propylthiouracil in man.
Authors: M Saberi, F H Sterling, R D Utiger
Journal: Journal of Clinical Investigation (1975)

To determine if propylthiouracil (PTU) inhibited extrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion in man, PTU was administered to T4-treated hypothyroid patients and serial measurements of T4, T3, and thyrotropin (TSH) carried out. All patients had proven thyroidal hypothyroidism and had been receiving 0.1 or 0.2 mg T4 daily for at least 2 mo before study. Hormone measurements were made for 5 consecutive days before and daily during a 7-day treatment period with PTU, 1,000 mg/day. In eight patients receiving 0.1 mg T4 daily, administration of PTU resulted in a prompt fall in mean serum T3 concentrations from 78 plus or minus 6 ng/100 ml (SEM) to 61 plus or minus 3 ng/100 ml after 1 day. The mean serum T3 concentrations ranged from 55 to 60 ng/100 ml during the remainder of the PTU treatment period (P less than 0.01). The mean control serum TSH concentration was 29.6 muU/ml and it increased to a peak of 40 muU/ml on the 5th and 6th days. In five patients receiving 0.2 mg T4 daily, the mean control serum T3 concentration was 84 plus or minus 7 NG/100ML. It fell to 70 plus or minus 5 ng/100 ml after 1 day and 63 plus or minus 7 ng/100 ml after 2 days of PTU administration and thereafter ranged from 6) to 69 ng/100 ml (P LESS THAN 0.01). Serum TSH concentrations did not increase. No changes in serum T4 concentrations were found in either group. In five patients who received 100 mg methimazole (MMI) daily for 7 days there were no changes in serum T4, T3, or TSH concentrations. These results indicate that PTU, but not MMI, produces a prompt and sustained, albeit modest, reduction in serum T3 concentrations in patients whose sole or major source of T3 is ingested T4. These findings most likely result from inhibition of extrathyroidal formation of T3 from T4.
Structure, Endothelial Function, Cell Growth, and Inflammation in Blood Vessels of Angiotensin II–Infused Rats
Authors: Quy N. Diep, Mohammed El Mabrouk, Jeffrey S. Cohn, Dierk Endemann, Farhad Amiri, Agostino Virdis, Mario Fritsch Neves, Ernesto L. Schiffrin
Journal: Circulation (2002)

Pioglitazone and rosiglitazone, thiazolidinedione peroxisome proliferator-activated receptor-gamma (PPARgamma) activators, reduce blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that pioglitazone or rosiglitazone would prevent BP elevation and vascular dysfunction in angiotensin (Ang) II-infused rats by direct vascular effects.Sprague-Dawley rats received Ang II (120 ng x kg(-1) x min(-1) SC) with or without pioglitazone (10 mg x kg(-1) x d(-1)) or rosiglitazone (5 mg x kg(-1) x d(-1)) for 7 days. Systolic BP, elevated in Ang II-infused rats (176+/-5 mm Hg) versus controls (109+/-2 mm Hg, P<0.01), was reduced by pioglitazone (134+/-2 mm Hg) or rosiglitazone (123+/-2 mm Hg). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (P<0.05) and acetylcholine-induced relaxation impaired in Ang II-infused rats (P<0.05); both were normalized by the thiazolidinediones. In Ang II-infused rats, vascular DNA synthesis (by 3H-thymidine incorporation); expression of cell cycle proteins cyclin D1 and cdk4, angiotensin II type 1 receptors, vascular cell adhesion molecule-1, and platelet and endothelial cell adhesion molecule; and nuclear factor-kappaB activity were increased. These changes were abrogated by pioglitazone or rosiglitazone.Thiazolidinedione PPAR-gamma activators attenuated the development of hypertension, corrected structural abnormalities, normalized cell growth, and improved endothelial dysfunction induced by Ang II and prevented upregulation of angiotensin II type 1 receptors, cell cycle proteins, and proinflammatory mediators. Thiazolidinediones may be useful in the prevention and/or treatment of hypertension, particularly when it is associated with insulin resistance or diabetes mellitus.
Abstract 1097: Potentiating antitumor CD4+ T cell responses with chemotherapeutic agents
Authors: Gang Zhou, Xiaoyun Lu
Journal: Cancer Research (2014)

Abstract Chemotherapy is a major treatment modality for many types of cancers. Even though chemotherapeutic drugs are chosen for their cytotoxicity toward cancerous cells, increasing numbers of anticancer drugs have been found to exert immune enhancing effects through a variety of mechanisms. These findings have led to a growing recognition that elicitation of endogenous host immunity may intrinsically contribute to the efficacy of some antineoplastic agents. Although standard chemotherapy can reduce the symptoms of cancer, chemotherapy alone is rarely curative. Tumor relapses often occur in patients after the initial treatment, suggesting that the endogenous antitumor immunity elicited by chemotherapy is not sufficient or durable enough to support long-term therapeutic efficacy. There is accumulating evidence that integration of chemotherapy and immunological maneuvers, such as adoptive T-cell therapy (ACT) and therapeutic vaccines, can effectively treat established tumors. In a mouse model of B-cell lymphoma, we previously reported that polyfunctional CD4+ effector cells arising from ACT play a critical role in sustaining an effective antitumor immunity in the post-chemotherapy setting. In the current study, we have screened a panel of widely used chemotherapeutic agents and identified those that can exert immunostimulatory effects on tumor-specific CD4+ T cells. We also examined the impact of these drugs on lymphoid and myeloid cell homeostasis, and cytokine/chemokine milieu. These data provide insight into the mechanisms by which certain anticancer drugs potentiate antitumor CD4+ T cell responses. Citation Format: Gang Zhou, Xiaoyun Lu. Potentiating antitumor CD4+ T cell responses with chemotherapeutic agents. [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 1097. doi:10.1158/1538-7445.AM2014-1097
Three-Dimensional Mapping of Gyral Shape and Cortical Surface Asymmetries in Schizophrenia: Gender Effects
Authors: Katherine L. Narr, Paul M. Thompson, Tonmoy Sharma, Jacob Moussai, Chris Zoumalan, Janice Rayman, Arthur W. Toga
Journal: American Journal of Psychiatry (2001)

People with schizophrenia exhibit abnormalities in brain structure, often in the left hemisphere. Disturbed structural lateralization is controversial, however, and effects appear mediated by gender. The authors mapped differences between schizophrenic and normal subjects in gyral asymmetries, complexity, and variability across the entire cortex.Asymmetry and shape profiles for 25 schizophrenic patients (15 men) and 28 demographically similar normal subjects (15 men) were obtained for 38 gyral regions, including the sylvian fissure and temporal and postcentral gyri, by using magnetic resonance data and a novel surface-based mesh-modeling approach. Cortical complexity was examined for sex and diagnosis effects in lobar regions. Intragroup variability was quantified and visualized to assess regional group abnormalities at the cortical surface.The patients showed greater variability in frontal areas than the comparison subjects. They also had significant deviations in gyral complexity asymmetry in the superior frontal cortex. In temporoparietal regions, significant gyral asymmetries were present in both groups. Sex differences were apparent in superior temporal gyral measures, and cortical complexity in inferior frontal regions was significantly greater in men.Cortical variability and complexity show regional abnormalities in the frontal cortex potentially specific to schizophrenia. The results indicate highly significant temporoparietal gyral asymmetries in both diagnostic groups, contrary to reports of less lateralization in schizophrenia. Substantially larger study groups are necessary to isolate smaller deviations in surface asymmetries, if present in schizophrenia, suggesting their diagnostic value is minimal.
Activity of Bosutinib, Dasatinib, and Nilotinib Against 18 Imatinib-Resistant BCR/ABL Mutants
Authors: Sara Redaelli, Rocco Piazza, Roberta Rostagno, Vera Magistroni, Pietro Perini, Manuela Marega, Carlo Gambacorti-Passerini, Frank Boschelli
Journal: Journal of Clinical Oncology (2008)
Pyrogenic Reactions Associated With the Reuse of Disposable Hollow-Fiber Hemodialyzers
Authors: Steven M. Gordon
Journal: JAMA (1988)

We investigated 18 pyrogenic reactions (PRs) that occurred between July 1 and 13,1987, in 16 patients receiving long-term hemodialysis at one dialysis center in Illinois. We defined a case of PR as the onset of chills or fever (oral temperature, ≥37.8°C) in a patient who was afebrile and had no signs or symptoms of infection before a dialysis treatment. Pyrogenic reactions to dialysis sessions during the epidemic period (July 1 through 14) were associated with the use of a reused dialyzer (risk ratio, 6.2; 95% confidence interval, 0.8 to 45). The water used to rinse the dialyzers after use and to dilute the germicide for disinfecting the dialyzers contained high concentrations of endotoxins (&gt;6 ng/mL) and bacteria (&gt;10<sup>4</sup>colony forming units/mL). After reuse of dialyzers was discontinued at the center, the PR rate fell to pre-epidemic levels. We concluded that PRs were associated with reuse of dialyzers, probably contaminated with endotoxins. Active surveillance for PRs among patients undergoing long-term hemodialysis should be routine at all dialysis centers; an increase in PRs should prompt timely review of water treatment and dialyzer reprocessing systems. (<i>JAMA</i>1988;260:2077-2081)
Management of an Outbreak of Tuberculosis in a Small Community
Authors: Ban Mishu Allos
Journal: Annals of Internal Medicine (1996)

Objective: To investigate an outbreak of tuberculosis, determine the number of active cases and infections, and examine efforts to control the spread of disease. Setting: A small town in Maine, in which no cases of tuberculosis had been reported in the previous 3 years. Design: Epidemiologic investigation of an outbreak of tuberculosis infection and disease. Measurements: A patient with an active case of tuberculosis was defined as a resident of the town or the surrounding area or an employee of the local shipyard who had a culture of sputum or tissue that was positive for Mycobacterium tuberculosis between June 1989 and May 1992. A case of tuberculous infection was defined as a positive tuberculin skin test result in a person with no previous positive test result. Results: 21 active cases of tuberculosis occurred among shipyard workers and persons residing in the affected community between 1989 and 1992. One patient was the source of the outbreak; 8 months lapsed between the onset of this patient's illness and appropriate diagnosis and treatment. The M. tuberculosis strains isolated from this patient and from six other patients belonged to phage type I, auxiliary 14. All isolates were susceptible to drug treatment. Of 9898 persons who were tested, 697 (7%) were newly infected. Because isoniazid prophylaxis was not routinely offered to infected persons older than 35 years of age, only 341 (49%) infected persons completed isoniazid prophylaxis. Conclusions: Many secondary cases of tuberculosis occurred throughout this small Maine community because of delayed diagnosis and treatment of the source patient, delayed outbreak investigation, and failure to promote isoniazid prophylaxis to all persons infected during the outbreak. Aggressive efforts to identify persons with new infection are of limited value in controlling tuberculosis unless they are accompanied by an equally aggressive use of isoniazid prophylaxis.
Early Potent Antithrombotic Effect With Combined Aspirin and a Loading Dose of Clopidogrel on Experimental Arterial Thrombogenesis in Humans
Authors: Yves Cadroy, Jean-Pierre Bossavy, Claire Thalamas, Luc Sagnard, Kjell Sakariassen, Bernard Boneu
Journal: Circulation (2000)

We conducted a double-blind, randomized, crossover study to assess the antithrombotic effects of the combination of aspirin (acetylsalicylic acid, ASA) and clopidogrel, with or without a loading dose, versus ASA alone in a model of arterial thrombosis in humans.Eighteen male volunteers received the following 3 regimens for 10 days separated by a 1-month period: (1) 325 mg ASA daily, (2) 325 mg ASA+75 mg clopidogrel daily, (3) 325 mg ASA daily+300-mg clopidogrel loading dose on day 1 and +75 mg clopidogrel per day on days 2 to 10. The antithrombotic effect was measured 1.5, 6, and 24 hours after drug intake on day 1 and 6 hours after drug intake on day 10. Arterial thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel-plate perfusion chamber to native blood for 3 minutes at an arterial wall shear rate. Without a loading dose, clopidogrel+ASA developed an antithrombotic effect within 6 hours after the first intake. It was superior to that produced by ASA, but it was moderate (P</=0.03). However, with the loading dose, the antithrombotic effect of clopidogrel+ASA appeared within 90 minutes, and after 6 hours it was comparable to that on day 10. On day 10, clopidogrel+ASA decreased platelet thrombus formation by approximately 70%, and the effect was significantly more potent than that produced by ASA alone (P<0.001).This study confirms the synergistic antithrombotic effects of a combined ASA and clopidogrel therapy and shows the early benefit obtained with a loading dose of clopidogrel.
A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer
Authors: Eric J. Small, Raymond S. Lance, Thomas A. Gardner, Lawrence I. Karsh, Lawrence Fong, Candice McCoy, Todd DeVries, Nadeem A. Sheikh, Debraj GuhaThakurta, Nancy Chang, Charles H. Redfern, Neal D. Shore
Journal: Clinical Cancer Research (2015)

Abstract Purpose: This phase II open-label study evaluated the effect of concurrent or sequential administration of abiraterone acetate plus prednisone (AA + P) on sipuleucel-T manufacture and immune responses in metastatic castration-resistant prostate cancer (mCRPC) patients. Experimental Design: mCRPC patients received sipuleucel-T followed by AA + P 1 day (concurrent) or 10 weeks (sequential) after the first sipuleucel-T infusion. AA + P treatment continued for 26 weeks. The primary endpoint was cumulative antigen presenting cell (APC) activation, and secondary endpoints included cumulative APC number and total nucleated cell counts. Additional endpoints included in vivo peripheral immune responses to sipuleucel-T (T-cell responses, T-cell proliferation, humoral responses, and antigen spread) as well as safety. Results: Sixty-nine mCRPC patients were enrolled, with 35 and 34 patients randomized to the concurrent and sequential arms, respectively. Ex vivo APC activation was significantly greater at the second and third infusions compared with baseline in both arms (P &amp;lt; 0.05), indicative of an immunologic prime-boost effect. In both arms, sipuleucel-T product parameter profiles and peripheral immune responses were consistent with previously conducted sipuleucel-T phase III trials. Antigen spread was similarly observed in both arms and consistent with the other immunologic endpoints. Conclusions: These data suggest that sipuleucel-T can be successfully manufactured during concurrent administration of AA + P without blunting immunologic effects or altering immune parameters that correlate with sipuleucel-T's clinical benefit. Combination of these agents was well tolerated, with no new safety signals emerging. Clin Cancer Res; 21(17); 3862–9. ©2015 AACR.
Authorised clinical staff need access to clinical information
Authors: D. Hutchon
Journal: BMJ (2002)

EDITOR—Rigby et al make the point that it is difficult to ensure appropriate levels of confidentiality in electronic information systems to the point that the highly exacting requirements being demanded by independent commentators and professional bodies are difficult to satisfy without jeopardising the functioning of core services.1 It is not clear, however, how the TEAC health project has addressed this problem.

Software from a single supplier should provide a totally integrated system, but it may not contain all …
Transmission of<i>Mycobacterium tuberculosis</i>Undetected by Tuberculin Skin Testing
Authors: Suzanne T. Anderson, Amanda J. Williams, Jillian R. Brown, Sandra M. Newton, Marcela Simsova, Mark P. Nicol, Peter Sebo, Michael Levin, Robert J. Wilkinson, Katalin A. Wilkinson
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The development of tuberculin skin test (TST) positivity following infection by Mycobacterium tuberculosis is not invariable and may depend on bacillary as well as host factors.First, to compare the diagnostic performance of the TST and a form of in vitro IFN-gamma release assay (IFNGRA) in the circumstances of a contact investigation prompted by an unusually severe index case of infectious pulmonary tuberculosis. Second, to investigate the ability of the strain of M. tuberculosis responsible to induce cytokine secretion from monocytes in vitro.A routine TST-based tuberculosis-contact screening procedure supplemented by the use of an "in house" IFNGRA that assays the T-cell response to the M. tuberculosis-specific antigens ESAT-6, CFP-10 (presented as a fusion protein within the inactivated adenylate cyclase of Bordetella pertussis), and purified protein derivative of M. tuberculosis. Isolation and genetic typing of the strain of M. tuberculosis responsible, and investigation of its ability to induce cytokine secretion from monocytes in vitro.TST screening suggested a low rate of transmission with just 2/75 unequivocally positive responses. By contrast, the IFNGRA suggested an infection rate of 16/75 (22%). When compared with two reference strains of M. tuberculosis (H37Rv and CDC1551), the outbreak strain induced lower levels of tumor necrosis factor-alpha and interleukin-12p40 (p < 0.04), cytokines associated with the development of delayed-type hypersensitivity.These data suggest that infection by M. tuberculosis can be undetected by TST, and that this may partially relate to strain differences in immunogenicity.