tbuckley/cabot-search huggingface dataset:
Validity of anecdotal reports of suspected adverse drug reactions: the problem of false alarms
Authors: G R Venning
Journal: BMJ (1982)

Suspected adverse drug reactions first reported in 1963 in the "British Medical Journal," the "Lancet," the "Journal of the American Medical Association," and the "New England Journal of Medicine" were reviewed 18 years later to assess their initial validity and subsequent verification. Of 52 first reports, five were deliberate investigations into potential or predictable reactions, and in each case causality was reasonably established; the other 47 reports were essentially anecdotal. Of these 47 reports, 14 related to categories of adverse reaction where false-positive reports were unlikely: immediate reactions, local reactions, and known reactions caused by a different mode of administration or a brand previously thought or claimed to be safe. The problem of false alarms rose in the remaining types of reactions: general reactions that did not occur immediately after administration and arose for the first time with a new chemical entity. Of 33 reports of such suspected adverse reactions, validity was satisfactorily established in 14 cases on the basis of rechallenge, predictability from known pharmacology, or the unique nature of the reaction. Of the remaining 19 reports, further verification still has not been satisfactorily established in 12. Seven of these possible false alarms were haematological reactions. Although 35 of the 47 anecdotal reports were clearly correct, of the 19 reports that were not reasonably validated at the time of the report, only seven were subsequently verified. This suggests that agencies monitoring adverse drug reactions should adopt criteria for assessing the validity of first reports of suspected adverse reactions. Such criteria should include: reactions on rechallenge, a pharmacological basis for the adverse reaction, immediate acute reactions, local reactions at the site of administration, reactions with a new route of administration of a drug known to provoke such reactions by another route, and the repeated occurrence of very rare events.
Levomethadyl in Maintenance Treatment of Opiate Dependence
Authors: Arthur Zaks
Journal: JAMA (1972)

In a comparison of methadone hydrochloride and levomethadyl acetate (I-alpha-acetylmethadol), 20 male, opiate-dependent subjects were assigned at random to either regimen. Methadone-treated subjects received methadone hydrochloride, 100 mg daily. Levomethadyl patients received doses on Monday, Wednesday, and Friday only. Four received low doses (30 to 50 mg), and six received high doses (80 mg). Both regimens were well tolerated. At six months, eight of ten methadone-treated patients and eight of nine levomethadyl-treated patients were undergoing treatment. In patient acceptance, withdrawal symptoms, response to heroin challenges, and number of positive results for urine tests measured for morphine, the two groups were equivalent. Levomethadyl acetate, 80 mg administered three times per week, is equivalent to daily administration of 100 mg of methadone hydrochloride. Large-scale clinical trials of levomethadyl acetate are suggested.
Abstract 2468: Selective aldosterone blocker inhibits murine hepatocellular carcinoma development via angiogenesis suppression
Authors: Kosuke Kaji, Hitoshi Yoshiji, Yasuhide Ikenaka, Ryuichi Noguchi, Yusaku Shirai, Hiroshi Fukui
Journal: Cancer Research (2010)

Abstract It is now widely recognized that angiogenesis is a crucial step in the development of tumors, including hepatocellular carcinoma (HCC). Therapies targeting the tumor vessels have proven successful for cancer treatment in experimental models and, in the clinical practice, several anti-angiogenic agents have already been employed. The renin-angiotensin-aldosterone system (RAAS) has also become known as a prerequisite for tumor angiogenesis, including HCC. We previously reported that angiotensin-II (AT-II) plays an important role in HCC development, and that suppression of AT-II by angiotensin-converting enzyme (ACE) inhibitor attenuated the tumor growth of HCC via suppression of intra-tumoral angiogenesis. Recent studies have also suggested the possible involvement of aldosterone (Ald) in neovascularization, although the actual role of Ald in tumor angiogenesis is still vague. The aim of our current study was to elucidate the effect of eplerenone (Epl), a clinically used selective Ald blocker, on HCC development, especially in conjunction with angiogenesis, using subcutaneous HCC model. To create an allograft model, we injected 1×106 of BNL-HCC cells into the flanks of BALB/c mice. The administration of Epl by daily gavage at a dose of 100 mg/kg/day was started on day 14, when the mean tumor volume was ∼ 200 mm3. The tumor volume was measured twice a week, and the mice were killed 35 days after tumor cell implantation. Administration of Epl at clinically comparable low dose could suppress HCC development as compared with the non-treated control. Epl treatment resulted in a marked increase of TUNEL-positive apoptosis in the tumor, whereas Ki67-positive tumor cell proliferation was not altered. Both CD31-immunopositive neo-vessels and VEGF expression in the tumor were markedly suppressed by this treatment in a magnitude similar to the inhibitory effect on the tumor growth. Our in-vitro study showed that Epl significantly suppressed the Ald-induced endothelial proliferation and tubular formation via inhibition of phosphorylation of the extracellular signal-regulated kinase 1/2. On the other hand, neither Ald nor Epl affected the proliferation of HCC cells. In conclusion, these results indicated that aldosterone plays a pivotal role in HCC development via VEGF-mediated tumor angiogenesis, and that Epl may be a potential new strategy for HCC therapy in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2468.
Concurrent Cisplatin, Etoposide, and Chest Radiotherapy in Pathologic Stage IIIB Non–Small-Cell Lung Cancer: A Southwest Oncology Group Phase II Study, SWOG 9019
Authors: Kathy S. Albain, John J. Crowley, Andrew T. Turrisi, David R. Gandara, William B. Farrar, Joseph I. Clark, Kristie R. Beasley, Robert B. Livingston
Journal: Journal of Clinical Oncology (2002)

PURPOSE: There are no published survival data after chemoradiotherapy (chemoRT) in pathologically documented stage IIIB non–small-cell lung cancer. Studies of radiotherapy (RT) alone or chemotherapy followed by RT yield 5-year survivals less than 10%. The Southwest Oncology Group (SWOG) employed the same concurrent chemoRT induction regimen used in its predecessor trimodality trial to determine the efficacy, safety, and long-term outcome of replacing postinduction surgery with additional chemoRT. PATIENTS AND METHODS: Eligible patients for SWOG-9019 had pathologic documentation of T4N0/1, T4N2, or N3 stage IIIB non–small-cell lung cancer. They had pulmonary function adequate to withstand combined-modality therapy, identical to the requirements of the previous trial with postchemoRT surgery. Induction therapy was two cycles of cisplatin plus etoposide (PE) concurrent with once-daily thoracic RT (45 Gy). In the absence of progressive disease, RT was completed to 61 Gy, with two additional cycles of cisplatin plus etoposide. RESULTS: Fifty eligible patients were accrued with tumor-node (TN) substage confirmed on central review: 18, T4N0/1; 12, T4N2; and 20, N3. Grade 4 neutropenia was the most common toxicity (32%). Grade 3/4 esophagitis occurred in 12% and 8%. Median follow-up was 52 months, and overall median survival was 15 months (10 to 22, 95% confidence interval). Three- and 5-year survivals were 17% and 15% (5-year T4N0/1, 17%; T4N2, 13%; and N3, 15%). CONCLUSION: Feasibility and long-term survival support the application of these results as a standard against which mature outcomes of chemoRT trials with new chemotherapy agents can be compared. These results also justify use of the SWOG-9019 approach as a control arm in ongoing phase III trials.
Myelodysplastic syndrome with an unbalanced 1;16 translocation in a case of early age of onset
Authors: Sarah Dean, Anwar N. Mohamed
Journal: American Journal of Hematology (2006)

Abstract We present a 30‐year‐old male patient diagnosed with myelodysplastic syndrome (MDS). Chromosome analysis of the bone marrow aspirate revealed a derivative chromosome resulting from an unbalanced 1;16 translocation causing the gain of 1q and loss of 16q. Dual color fluorescence in situ hybridization demonstrated that the 1q;16p derivative chromosome contained centomeric material derived from chromosome 1, and accordingly the translocation was designated as a der (1)t(1;16)(p11;p11.1). Review of literature revealed that 1;16 translocation in MDS is nonrandom and is always described as unbalanced, resulting in trisomy 1q and monosomy 16q. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
THE USE OF PRECIPITIN ANALYSIS IN AGAR FOR THE STUDY OF HUMAN STREPTOCOCCAL INFECTIONS
Authors: S. P. Halbert, T. Auerbach
Journal: The Journal of Experimental Medicine (1961)

Studies on the purification of group A streptococcal extracellular antigens detectable with naturally occurring human antibodies from normal individuals have been extended. It has been shown that streptococcal electrophoretic fractions intermediate between the most rapidly migrating components are quite complex. In the calcium phosphate chromatography of adjacent electrophoretic fractions, particular antigenic components desorbed at similar buffer elution steps. It is clear from the results obtained that substantially more extracellular antigens than the twelve heretofore recognized are secreted in human beings during infection, as judged by their detection with human antibodies. The precise number is not yet known, but is probably greater than 16. Of the nine components which thus far have been separated rather well from the others, four were previously identified as streptolysin "O," diphosphopyridine nucleotidase, proteinase precursor, and desoxyribonuclease B. The accumulated data substantiated these previous identifications. The identity of a fifth antigen has been made as a possible complex of C carbohydrate and protein. Tentative evidence for the relationship of a sixth component to scarlet fever toxin has been presented. It has been shown that rechromatography of crystalline proteinase precursor and desoxyribonuclease B on calcium phosphate columns resulted in elution principally at the expected stepwise increase in buffer concentration. Attempts to isolate antigens present as mixtures in some calcium phosphate chromatographic peaks, by rechromatography on DEAE or CM cellulose columns resulted in only limited further purifications.
Difference in clinical features and HLA antigens between familial and non-familial vitiligo of non-segmental type
Authors: I. ANDO, H-I. CHI, H. NAKAGAWA, F. OTSUKA
Journal: British Journal of Dermatology (1993)

Of 131 patients with non‐segmental vitiligo studied, 29 (22%) had a family history of this disorder. The clinical features and HLA antigens were assessed, and a comparison made between patients with familial and those with non‐familial, non‐segmental vitiligo. Familial patients developed skin lesions significantly earlier than non‐familial patients. There was a significant association between HLA‐B46 and familial non‐segmental vitiligo, whereas HLA‐A31 and CW4 were found in non‐familial patients. The differences in clinical features and HLA phenotypes suggest heterogeneity in the pathogenic process between familial and non‐familial vitiligo patients.
Cholesterol in the lungs of heavy cigarette smokers.
Authors: B Corrin, S S Soliman
Journal: Thorax (1978)

Electron microscopy of "normal" lung tissue from four heavy cigarette smokers showed acicular crystal clefts thought to represent cholesterol in the cytoplasm of virtually every type II pneumocyte. Similar but less pronounced changes were found in two cases of obstructive pneumonia distal to bronchial tumours, a condition characterised by excess cholesterol. Cholesterol pneumonitis is particularly prevalent in smokers, and the changes in our smokers' lungs possible represent an early stage in a process that if progressive would lead to this disease. The cholesterol may represent a degenerative change in type II pneumocytes or a byproduct of increased surfactant synthesis stimulated by cigarette smoke.
Abstract 2075: Resistin promotes MMP-2 production and migration in human chondrosarcoma cells through AMPK/p38/mir 519d pathway
Authors: Ho-Ning Huang, Chih-Hish Tang, Yuan-Li Huang
Journal: Cancer Research (2014)

Abstract Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Resistin the most potent pro-inflammatory and plays a crucial role in migration and metastasis of human cancer cells. However, the effects of resistin on human chondrosarcoma cells are largely unknown. In this study, we found that treatment of human chondrosarcoma cells (JJ012) with resistin increased migration and expression of matrix metalloproteinase (MMP)-2. Resistin-mediated cell migration and MMP-2 expression were reduced by pretreatment with inhibitors of AMP-activated protein kinase (AMPK), and p38 mitogen-activated protein kinases (p38). Resistin treatment induced phosphorylation of AMPK and p38. In addition, resistin reduced miRNA 519d expression. Transfect ion of 519d mimic also reduced resistin mediated migration and MMP2 expression. Furthermore, we analyzed samples from chondrosarcoma patients by immunohistochemical staining. The expression of resistin and MMP2 in chondrosarcoma patients was significantly higher than in normal cartilage. Taken together, these results suggest that resistin increased MMP-2 expression and migration in human chondrosarcoma cells. Citation Format: Ho-Ning Huang, Chih-Hish Tang, Yuan-Li Huang. Resistin promotes MMP-2 production and migration in human chondrosarcoma cells through AMPK/p38/mir 519d pathway. [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 2075. doi:10.1158/1538-7445.AM2014-2075
Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells
Authors: Laure A. Moutouh-de Parseval, Dominique Verhelle, Emilia Glezer, Kristen Jensen-Pergakes, Gregory D. Ferguson, Laura G. Corral, Christopher L. Morris, George Muller, Helen Brady, Kyle Chan
Journal: Journal of Clinical Investigation (2008)

Sickle-cell disease (SCD) and beta thalassemia constitute worldwide public health problems. New therapies, including hydroxyurea, have attempted to augment the synthesis of fetal hemoglobin (HbF) and improve current treatment. Lenalidomide and pomalidomide are members of a class of immunomodulators used as anticancer agents. Because clinical trials have demonstrated that lenalidomide reduces or eliminates the need for transfusions in some patients with disrupted blood cell production, we investigated the effects of lenalidomide and pomalidomide on erythropoiesis and hemoglobin synthesis. We used an in vitro erythropoiesis model derived from human CD34+ progenitor cells from normal and SCD donors. We found that both compounds slowed erythroid maturation, increased proliferation of immature erythroid cells, and regulated hemoglobin transcription, resulting in potent induction of HbF without the cytotoxicity associated with other HbF inducers. When combined with hydroxyurea, pomalidomide and, to a lesser extent, lenalidomide were found to have synergistic effects on HbF upregulation. Our results elucidate what we believe to be a new mechanism of action of pomalidomide and lenalidomide and support the hypothesis that pomalidomide, used alone or in combination with hydroxyurea, may improve erythropoiesis and increase the ratio of fetal to adult hemoglobin. These findings support the evaluation of pomalidomide as an innovative new therapy for beta-hemoglobinopathies.
Psychosocial stress in pregnancy.
Authors: F H Creed
Journal: BMJ (1979)

was about two-and-a-half times as large as the corresponding US study from the National Institute of Child Health and Development7 8 and at least as much care was taken to avoid biased assessments as in that study; there were no matched controls in the Canadian study.9It would thus not be surprising if the MRC study proved to be a more sensitive indicator of the possible risks of amniocentesis than either of the other two.The findings, which differ in several respects from those of the US study, certainly deserve more careful consideration than this premature and sweeping dismissal from the United States accorded them.
Palestine: the assault on health and other war crimes: Personal view from Israel
Authors: Alexander J Lustman
Journal: BMJ (2004)

EDITOR—As a doctor who has worked in Israel for 10 years, I am astounded that such one sided political views as those of Summerfield could be printed in such a distinguished medical journal.1 I have spent the past five years working in Ramla—a mixed Arab and Jewish town with a patient list of over 30% Arabs. I have …
Antigen-primed CD8+ T cells are necessary for the development of airway hyperresponsiveness and airway inflammation
Authors: N. Miyahara, K. Takeda, T. Kodama, A. Joetham, A. Dakhama, C. Taube, J. Park, A. Balhorn, E.W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2003)
Eosinophilia, meningitis and pulmonary nodules in a young woman
Authors: P. E. Pfeffer, A. Sen, S. Das, M. Sheaff, A. Sivaramakrishnan, D. E. Simcock, B. Turner
Journal: Thorax (2010)

A 22-year-old woman was admitted unwell with headache, fever and encephalopathy. She was born in the UK to parents from Hong Kong. She had a past history of asthma, perennial rhinitis and atopic dermatitis for which she took a budesonide 100 μg turbohaler and beclomethasone nasal spray. Three weeks before admission she had returned from holiday in Valencia and shortly after her return developed a flu-like illness followed by worsening asthma symptoms. Despite increasing usage of her corticosteroid turbohaler to eight puffs a day, her cough and wheeze worsened. Her GP prescribed a 5-day course of prednisolone 50 mg daily (approximately 1 mg/kg). Her asthma symptoms improved but she developed a headache 2 days after finishing the corticosteroid course. Over the next 5 days she became more unwell with worsening headache …
Heterogeneity of myosin isozyme content of rabbit heart.
Authors: R Z Litten, B J Martin, R H Buchthal, R Nagai, R B Low, N R Alpert
Journal: Circulation Research (1985)

A detailed study was carried out to measure the relative contents of V1 and V3 myosin isozymes in different regions of rabbit ventricle as a function of age, to assess animal-to-animal variability, and to compare different experimental approaches aimed at minimizing the effects of such variability. In addition, comparisons were made in normal developing hearts between ventricular isozyme composition and myofibrillar myosin calcium-stimulated adenosine triphosphatase. V1 isozyme predominated relative to V3 isozyme in the hearts of 2-week-old rabbits, decreasing to become a minor component in 10-week-old animals. Despite this trend, there was considerable variability in relative isozyme content of whole ventricular tissue among different rabbits of the same age. This variability was reduced in comparisons of littermates and by use of cardiac biopsies to measure changes in isozyme content in the same animal over time. Within different regions of a given heart, there also were small but significant differences in the percent V1 isozyme. The percent V1 was greatest for right ventricular papillary, followed by right ventricular free wall and then the left ventricle (free wall plus septum). There also were differences in the percent V1 within those regions, as exemplified by the significantly higher values for ventricular epicardium vs. endocardium. There was a linear correlation between the myofibrillar myosin calcium-stimulated adenosine triphosphatase and percent V1 of total isozyme for both right and left ventricles in normal and developing hearts. The regression lines for calcium-stimulated adenosine triphosphatase vs. percent V1 had a steeper slope in the left than in the right ventricle.
Impaired vagus nerve-mediated control of insulin secretion in Wistar fatty rats
Authors: Keiichi Yamatani, Hiroshi Ohnuma, Akira Niijima, Masahiko Igarashi, Kazuhiko Sugiyama, Makoto Daimon, Hideo Manaka, Makoto Tominaga, Hideo Sasaki
Journal: Metabolism (1998)
Secondary prevention of heart disease with statins
Authors: James Penston
Journal: BMJ (2005)

Secondary prevention of heart disease with statins Groups were as different as chalk and cheeseEditor-Wei et al say that the results of their observational study of treatment with statins in routine clinical practice in Tayside are consistent with, and similar to, those reported in clinical trials. 1 This conclusion is hardly justified.A cohort of patients, defined by a discharge diagnosis of myocardial infarction between January 1993 and December 2001, was studied to compare the outcomes in those treated with statins and those not receiving these drugs.The data clearly show that the two groups differed substantially in terms of age, sex, comorbidity, and other cardiovascular drug treatment-all of these factors were biased in favour of a poorer outcome in patients not given statins.Furthermore, the two groups belonged to different time periods, most of the untreated patients to the earlier part and most of those given statins to the later part of the study.Given the changes between 1993 and 2001-including, for example, those related to the management of acute myocardial infarction and the criteria for diagnosis-it is only to be expected that the untreated group would have a higher risk of subsequent cardiovascular events.Multivariate analysis was reported as showing that statins reduced all cause mortality by 31% and the composite end point of myocardial infarction plus cardiovascular mortality by 18%.These results should be greeted with scepticism.Firstly, many trials of statins have failed to show any reduction whatsoever in all cause mortality. [2]][4][5] Secondly, as observed in other studies, any reduction in all cause mortality would be expected to be much less than that for composite cardiovascular end points. 2 4 5 The two groups in this study were as different as chalk and cheese.It should come as no surprise, therefore, that the results were anomalous.In such circumstances, no amount of statistical trickery could be expected to furnish anything of value.
ETS factors reprogram the androgen receptor cistrome and prime prostate tumorigenesis in response to PTEN loss
Authors: Yu Chen, Ping Chi, Shira Rockowitz, Phillip J Iaquinta, Tambudzai Shamu, Shipra Shukla, Dong Gao, Inna Sirota, Brett S Carver, John Wongvipat, Howard I Scher, Deyou Zheng, Charles L Sawyers
Journal: Nature Medicine (2013)
Issues in the Organization of Medical Care
Authors: Richard N. Podell
Journal: New England Journal of Medicine (1971)

Abstract The podiatrist in the United States is a highly trained health worker who in the scope of his practice, independence of judgment and financial rewards is very similar to the physician. Nevertheless, the proper role of podiatry in health care remains controversial. By examination of the profession of podiatry a different perspective can be obtained upon some of the controversial issues in health-care organization that face the medical profession as well.