tbuckley/cabot-search huggingface dataset:
Hereditary Paralysis Agitans Cured (?) by Nasal Treatment.
Authors: Edward J. Brown
Journal: JAMA (1899)

Minneapolis, Minn., Dec. 26, 1898. <h3>To the Editor:</h3> —Mr. O. H. P., 34 years of age, a very intelligent mechanic, consulted me June 9, 1892, complaining that he had developed in connection with a series of severe colds in the head, a hereditary tendency to shaking of the head. Mr. P. is a man of fine physique and in good general health, which has continued to the present writing, six and a half years. The family history is as follows: His mother died of internal cancer, in her 63d year. His two brothers, his father, two paternal uncles and four paternal aunts (with one or two exceptions), his great-grandfather and the latter's brothers and sisters (with one or two exceptions), farther back he has no knowledge, all began to shake between the ages of 30 and 40 years. One sister of Mr. P. had temporary relief for about one year,
BMA president warns doctors not to take public esteem for granted
Authors: R. Smith
Journal: BMJ (2001)

Doctors should not take their public esteem for granted and should be careful about exaggerating the difficulties faced by the NHS. These were two of the main messages delivered by David Carter, the former chief medical officer of Scotland and now president of the BMA, at his inauguration at the BMA's annual meeting at Bournemouth.

“We have not been fleet of foot,” said Professor Carter, “in keeping up with public expectations.” Doctors should recognise that the world has changed dramatically. Professor Carter described attending a meeting with …
Physician-patient communication. The relationship with malpractice claims among primary care physicians and surgeons
Authors: W. Levinson
Journal: JAMA (1997)

To identify specific communication behaviors associated with malpractice history in primary care physicians and surgeons.Comparison of communication behaviors of "claims" vs "no-claims" physicians using audiotapes of 10 routine office visits per physician.One hundred twenty-four physician offices in Oregon and Colorado.Fifty-nine primary care physicians (general internists and family practitioners) and 65 general and orthopedic surgeons and their patients. Physicians were classified into no-claims or claims (> or =2 lifetime claims) groups based on insurance company records and were stratified by years in practice and specialty.Audiotape analysis using the Roter Interaction Analysis System.Significant differences in communication behaviors of no-claims and claims physicians were identified in primary care physicians but not in surgeons. Compared with claims primary care physicians, no-claims primary care physicians used more statements of orientation (educating patients about what to expect and the flow of a visit), laughed and used humor more, and tended to use more facilitation (soliciting patients' opinions, checking understanding, and encouraging patients to talk). No-claims primary care physicians spent longer in routine visits than claims primary care physicians (mean, 18.3 vs 15.0 minutes), and the length of the visit had an independent effect in predicting claims status. The multivariable model for primary care improved the prediction of claims status by 57% above chance (90% confidence interval, 33%-73%). Multivariable models did not significantly improve prediction of claims status for surgeons.Routine physician-patient communication differs in primary care physicians with vs without prior malpractice claims. In contrast, the study did not find communication behaviors to distinguish between claims vs no-claims surgeons. The study identifies specific and teachable communication behaviors associated with fewer malpractice claims for primary care physicians. Physicians can use these findings as they seek to improve communication and decrease malpractice risk. Malpractice insurers can use this information to guide malpractice risk prevention and education for primary care physicians but should not assume that it is appropriate to teach similar behaviors to other specialty groups.
An inhibitor of inducible nitric oxide synthase decreases forearm blood flow in patients with congestive heart failure
Authors: Yutaka Ishibashi, Toshio Shimada, Yo Murakami, Nobuyuki Takahashi, Takeshi Sakane, Takashi Sugamori, Shuzo Ohata, Shin-ichi Inoue, Yoko Ohta, Ko Nakamura, Hiromi Shimizu, Harumi Katoh, Michio Hashimoto
Journal: Journal of the American College of Cardiology (2001)
Allergy to systemic and intralesional corticosteroids
Authors: L. RASANEN, T. HASAN
Journal: British Journal of Dermatology (1993)

In this study, allergic reactions to systemic or intralesional corticosteroids were characterized, and skin tests utilized in the diagnosis of corticosteroid allergy. Five patients who had developed a rash when treated with systemic or intralesional hydrocortisone, methylprednisolone, prednisolone or betamethasone, were challenged with oral or intra-articular corticosteroid preparations, and skin tested. Upon provocation the patients reacted with diffuse erythema principally on the trunk or on the face. The erythema appeared within a period ranging from a few hours to 24 h and faded in 1-3 days. On patch testing, one patient reacted to prednisolone and methylprednisolone, which induced a positive response upon provocation, and two patients were positive to Pivalone. Patients who were sensitive to hydrocortisone or methylprednisolone, as judged by anamnestic data and provocations, reacted to these corticosteroids in the intradermal tests. Allergy to betamethasone could not be verified by intradermal or patch tests. A combination of intradermal and patch tests is recommended when allergy to systemic or intralesional corticosteroids is suspected. If these skin tests remain negative, provocation is the method of choice.
Authors' reply to Evans and Allen
Authors: P. G. Griffiths, L. M. Henderson, R. H. Taylor, B. Barrett
Journal: BMJ (2014)

We thank Professors Evans and Allen for their interest in our article.1 2

The charity websites we reviewed refer to colour as though it offers a scientific, evidence based treatment; none referred to feedback from the membership. For example, one charity website makes the claim that “Research in the UK and in Australia shows that people who need coloured filters, who are said …
Genetic differences in susceptibility to chemically induced myelotoxicity and leukemia.
Authors: D W Nebert
Journal: Environmental Health Perspectives (1981)

The Ah locus represents a complex "cluster" of genese controlling the induction of numerous drug-metabolizing enzyme "activities" by polycyclic aromatic compounds. Allelic differences at the Ah locus are reflected in the large differences in inducibility of cytochrome P1-450 and benzo[a]pyrene metabolism in numerous tissues when the mice receive the chemical daily in their diet. This experimental model system offers to the hematologist and clinical pharmacologist a means to study genetic differences in toxic chemical depression of the bone marrow, as well as a potential model to study aplastic anemia and leukemia explainable on a single-gene basis. The genetically "responsive" individual who is at increased risk for cancer caused by subcutaneous or topical or intratracheal polycyclic hydrocarbons is at decreased risk for toxicity of the bone marrow and leukemia caused by oral benzo[a]pyrene (when compared with the genetically "nonresponsive" individual receiving the same dose of the same xenobiotic). In other words, tissue sites in direct contact with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dct with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dct with the carcinogen develop cancer in responsive animals because of induced P1-450; tissues in distant sites of the body may develop malignancy in nonresponsive animals because more carcinogen reaches that tissue due to decreased P1-450 induction all over the body and therefore decreased detoxication. Not only the dose but the route of administration and the tissue in which the malignancy or toxicity develops are therefore very important in the interpretation of data from tumorigenesis or toxicity experiments involving P1-450 inducers such as polycyclic hydrocarbons. There exists sufficient evidence that heritable variation of the Ah locus occurs in man. Growing evidence indicates that persons with higher aryl hydrocarbon hydroxylase inducibility in their cultured mitogen-activated lymphocytes may have a statistically significantly increased risk for certain types of cancer and drug toxicity. It remains to be determined at the present time, however, whether this genotype can be used as a biochemical marker in the individual patient for predicting increased susceptibility to certain types of environmentally caused cancers or toxicity in man.
Genetic Polymorphisms in the Precursor MicroRNA Flanking Region and Non–Small Cell Lung Cancer Survival
Authors: Zhibin Hu, Yongqian Shu, Yijiang Chen, Jiaping Chen, Jing Dong, Yao Liu, Shiyang Pan, Lin Xu, Jing Xu, Yi Wang, Juncheng Dai, Hongxia Ma, Guangfu Jin, Hongbing Shen
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Previously, we reported that common variants in precursor microRNA (pre-miRNA) sequences played a role in the prediction of non-small cell lung cancer (NSCLC) survival.To assess whether variants in the pre-miRNA flanking region can influence the clinical behavior of NSCLC.We conducted a two-stage study to examine the impact of a panel of 85 single-nucleotide polymorphisms on the overall survival of 923 patients with NSCLC (568 in the screening set and 355 in the validation set) in China.Eleven single-nucleotide polymorphisms were primarily associated with NSCLC survival in the univariate analysis. However, in the validation set, only miR-30c-1 rs928508 was consistently an NSCLC survival predictor and the protective role of rs928508 AG/GG genotypes was more pronounced among early-stage (stage I/II) patients and patients treated with surgery. The area under the curve at Year 5 was significantly increased from 0.658 to 0.741 after adding the miR-30c-1 rs928508 risk score to the traditional clinical risk score (stage and surgery). Furthermore, in the genotype-phenotype correlation analysis, rs928508 AG/GG genotypes were associated with a significantly decreased expression of precursor and mature miR-30c (P = 0.009 and 0.011), but not with that of its primary miRNA. The expression of the host nuclear transcription factor Y gene was correlated with pri-mir-30c-1, but not with rs928508 genotypes, implicating the coregulation of the transcription of nuclear transcription factor Y and pri-mir-30c-1.Our data indicated, for the first time, that genetic polymorphisms in the pre-miRNA flanking region may be prognostic biomarkers of NSCLC, and rs928508 is such a potential candidate.
Abstract 2868: Pancreatic tumor stromal cells express high levels of α-glutamyl transferase that may be employed to deliver a metabolism inhibitor to the tumor mass
Authors: Emma E. Ramsay, Stéphanie Decollogne, Swapna Joshi, Alessandro Corti, Alfonso Pompella, Minoti Apte, Philip J. Hogg, Pierre J. Dilda
Journal: Cancer Research (2012)

Abstract Tumors of the pancreas have the most prominent stromal/desmoplastic reaction of all epithelial tumors. This reaction is mediated by the cancer-associated stellate cells. These cells interact closely with pancreatic cancer cells to promote cancer cell survival, local tumor growth and distant metastasis (1). We have found that cancer-associated human pancreatic stellate cells express up to 30-fold higher levels of α-glutamyl transferase (≥GT) on their surface than normal pancreatic stellate cells. βGT catalyzes the transfer of the α-glutamyl moiety of glutathione to an acceptor that may be an amino acid, a peptide or water (forming glutamate). This observation suggests that this enzyme could be used to deliver a αGT-activated prodrug to the tumor mass. We have tested this theory using the glutathionylated arsenical, GSAO. GSAO is converted to GCAO by cell surface αGT, which then crosses the plasma membrane and inactivates the mitochondrial inner-membrane transporter, adenine nucleotide translocase (2). The mitochondrial perturbation leads to proliferation arrest and then cell death. GSAO was converted to GCAO by cancer-associated stellate cells and this metabolism was blocked by the αGT inhibitor, ABBA. The activated GSAO inhibited proliferation of both tumor and endothelial cells by 43 to 100% and 41 to 75%, respectively. We also observed a positive correlation (R2=0.883) between the αGT activity of pancreatic tumor cells and proliferation arrest of co-cultured endothelial cells by GSAO. We have established an orthotopic model of human pancreatic cancer in mice where tumor cells are implanted without or with cancer-associated stellate cells. The anti-tumor efficacy of systemically administered GSAO is currently being evaluated in this model. These observations suggest that the high expression of αGT on pancreatic tumor stromal cells may be employed to deliver a αGT-activated prodrug to the tumor mass. 1. Vonlaufen, A., Phillips, P. A., Xu, Z., Goldstein, D., Pirola, R. C., Wilson, J. S., and Apte, M. V. (2008) Cancer Res. 68, 7707-7710 2. Dilda, P. J., Ramsay, E. E., Corti, A., Pompella, A., and Hogg, P. J. (2008) J. Biol. Chem. 283, 35428-35434 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2868. doi:1538-7445.AM2012-2868
Peripheral blood lymphocyte response to phytomitogens in systemic lupus erythematosus
Authors: B. Foad, L.E. Adams, A. Litwin, E.V. Hess
Journal: Annals of the Rheumatic Diseases (1976)

<b>Foad, B., Adams, L. E., Litwin, A., and Hess, E. V. (1976).</b><i>Annals of the Rheumatic Diseases</i>, <b>35</b>, 407-414. <b>Peripheral blood lymphocyte response to phytomitogens in systemic lupus erythematosus.</b> The response of peripheral blood lymphocytes to the phytomitogens, PHA, Con A, and PWM, was evaluated in 30 SLE patients and in 30 age, sex, and race-matched controls using dose and time responses. The proliferative response to the three phytomitogens was not depressed in this group of subacute and chronic SLE patients. Active lupus nephritis and a slow acetylator phenotype were associated with a decreased lymphocyte response. The incidence of a slow acetylator phenotype in spontaneous SLE was 68%. In interpreting the lymphocyte response to phytomitogens, the importance of a clear definition of the SLE group under study, the activity of the disease, and treatment status are emphasized.
TCT-340 Comparison of Fractional Flow Reserve, Instantaneous Wave-Free Ratio, and Hyperemic Instantaneous Wave-Free Ratio Values in Patients with Intermediate Coronary Stenosis
Authors: Yasutsugu Shiono, Takashi Kubo, Makoto Orii, Kunihiro Shimamura, Yamano Takashi, Yoshiki Matsuo, Yasushi Ino, Tomoyuki Yamaguchi, Kumiko Hirata, Atsushi Tanaka, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2014)
The General Practitioner of the Future
Authors: George James
Journal: New England Journal of Medicine (1964)

STUDIES by Weiskotten1 and others have documented the decline in the percentage of American physicians in general practice in recent years. That this is an era when specialization has glamor there is no doubt. It is known that most prospective physicians who choose to be specialists make their choice in medical school or during internship. Certainly in medical school there is generally less exposure to the need for the general practitioner than for the specialist. As for internship, Haggerty2 makes the following observation:Except in community hospitals, the intern may not even contact any family doctors, and when he does, . . .
Blood Pressure and Calcium Supplementation
Authors: Francesco P. Cappuccio
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Given the controversy over possible effects of calcium supplementation on high blood pressure,<sup>1-4</sup>rigorously designed and carefully presented studies are needed to answer such a basic question as whether oral calcium does or does not lower high blood pressure. In this regard, we wish to comment on the article by Lyle et al.<sup>5</sup> The authors' choice of a normotensive population, with an average baseline blood pressure below 120/75 mm Hg, does not appear to be appropriate for providing the answer to this question, despite the finding of "statistically significant" falls in blood pressure of 2.3 to 2.8 mm Hg. Furthermore, the presentation of the data is puzzling: since the placebo and calcium groups within each racial group were comparable in terms of blood pressure, age, body weight, and plasma and urinary variables, the need for adjusting the data on blood pressure, urinary variables, and even
Respiratory effects are associated with the number of ultrafine particles.
Authors: A Peters, H E Wichmann, T Tuch, J Heinrich, J Heyder
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The association between fine and ultrafine particles and respiratory health was studied in adults with a history of asthma in Erfurt, Eastern Germany. Twenty-seven nonsmoking asthmatics recorded their peak expiratory flow (PEF) and respiratory symptoms daily. The size distribution of ambient particles in the range of 0.01 to 2.5 microm was determined with an aerosol spectrometer during the winter season 1991-1992. Most of the particles (73%) were in the ultrafine fraction (smaller than 0.1 microm in diameter), whereas most of the mass (82%) was attributable to particles in the size range of 0.1 to 0.5 microm. Because these two fractions did not have similar time courses (correlation coefficient r = 0.51), a comparison of their health effects was possible. Both fractions were associated with a decrease of PEF and an increase in cough and feeling ill during the day. Health effects of the 5-d mean of the number of ultrafine particles were larger than those of the mass of the fine particles. In addition, the effects of the number of the ultrafine particles on PEF were stronger than those of particulate matter smaller than 10 microm (PM10). Therefore, the present study suggests that the size distribution of ambient particles helps to elucidate the properties of ambient aerosols responsible for health effects.
Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: A comparison
Authors: M J Tong, L M Blatt, J G McHutchison, R L Co, A Conrad
Journal: Hepatology (1997)

Patients with chronic hepatitis C (n = 103) were treated for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in determining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treatment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete responders. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treatment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is practical, cost-efficient and beneficial both to patients and to third-party payers.
Studies of the immunoglobulin-producing cells of the human intestine: the defunctioned bowel.
Authors: S S Wijesinha, H W Steer
Journal: Gut (1982)

<h3>Abstract</h3> Dysregulated protein synthesis is seen in many aggressive cancers, including metastatic breast cancer. However, the specific contributions of certain translation initiation factors to in vivo disease remain undefined. This is particularly true of eIF4B, an RNA-binding protein and cofactor of the RNA helicase eIF4A and associated eIF4F cap-binding complex. While eIF4A, eIF4G, and eIF4E are well-known to contribute to the progression of many cancer types including metastatic breast cancers, the role played by eIF4B in breast cancer remains relatively unclear. We therefore explored how naturally divergent and experimentally modulated eIF4B levels impact tumor growth and progression in well-characterized murine triple negative breast cancer (TNBC) models. Surprisingly, we found that higher eIF4B levels in mouse and human breast cancers were associated with less aggressive phenotypes. shRNA-mediated eIF4B knockdown in TNBC lines failed to markedly alter proliferation and global translation in the cells in vitro and only modestly hindered their growth as primary mammary tumors growth in mice. However, eIF4B knockdown significantly enhanced invasive growth in vitro and exacerbated both tumor burden and mortality relative to nontargeting shRNA controls in a model of metastatic disease. Analysis of eIF4B levels and breast cancer patient survival reinforced a link to better outcomes. Interestingly, low eIF4B expression was also associated with more formidable immune evasion in vitro and in vivo, implicating a novel immunomodulatory role for this factor in the malignant setting that suggests a mode of action beyond its historical role as a co-activator of eIF4A/F. <h3>Significance Statement</h3> Metastasis is the leading cause of cancer-related mortality. Despite many advances in our understanding of this complex process and the molecular and cellular events involved, mechanisms that allow secondary tumors to arise and persist remain incompletely understood. Uncharacterized metastatic determinants active at the level of translational control may be exploitable as novel therapy targets or biomarkers predicting a tumor’s potential for spread and recurrence. Here we describe previously unrecognized consequences of dysregulated eIF4B levels in murine breast cancer that shed light on how this translation initiation factor contributes to disease outcomes. Our findings suggest that eIF4B levels direct metastatic risk and immune evasion, and further study should establish its value in personalized treatment decisions and development of future therapies.
Importance of lumbar puncture in diagnosing subarachnoid haemorrhage
Authors: C. E. Uff, C. Harrison
Journal: BMJ (2013)

The recent National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report into the management of patients with aneurysmal subarachnoid haemorrhage in the UK was published on 22 November and subsequently reported in the BMJ .1 2 One of its main …