tbuckley/cabot-search huggingface dataset:
Evidence for linkage of red blood cell size and count: Genome‐wide scans in the Framingham Heart Study
Authors: Jing‐Ping Lin, Christopher J. O'Donnell, Li Jin, Caroline Fox, Qiong Yang, L. Adrienne Cupples
Journal: American Journal of Hematology (2007)

Abstract Red blood cell (RBC) count and size are major criteria for evaluating anemia and related hematology disease diagnoses. While environmental factors influence RBC count (RBCC) and size, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), studies have indicated that each of these measures has a substantial genetic component. So far, no linkage analysis or genome scan has been reported. We carried out 10 cM genome‐wide scans on RBCC, MCV, and MCH in a community‐based Caucasian cohort, the Framingham Heart Study, using 325 pedigrees with 1,144 individuals genotyped and phenotyped. Using variance‐component linkage methods, heritabilities were estimated as 56, 52, and 52% after covariate adjusted for RBCC, MCV, and MCH, respectively. For RBCC, we found a maximum LOD score of 3.2 on chromosome 19, 24 cM (7.0 Mbp). Near this region, there lie a few important candidate genes, including erythropoietin receptor and erythroid Krüppel‐like factor. For linkage analyses for MCV and MCH, there were coinciding maximized LOD scores on chromosome 11, 9 cM (5.2 Mbp) with values of 3.8 and 3.6, respectively. Under the peak resides the hemoglobin β cluster ‐ several β‐like genes, which are important candidates for RBC size. In subsequent analyses, we excluded individuals with low MCV to assess the possible influence of β‐thalassemia carriers, and there continued to be evidence for linkage in the same region on chromosome 11p15 (LOD scores of 2.6 and 2.7 for MCV and MCH, respectively). For MCV, we also identified a new region on chromosome 6q24 with a LOD score of 2.9. These findings suggest that further studies are warranted to identify potential causal genetic variants for RBC size and count and related erythrocyte indices. Am. J. Hematol., 2007. Published 2007 Wiley‐Liss, Inc.
Acute severe asthma treated by mechanical ventilation: 10 years' experience from a district general hospital.
Authors: A R Luksza, P Smith, J Coakley, I J Gordan, S T Atherton
Journal: Thorax (1986)

A retrospective study was made of patients requiring mechanical ventilation (intermittent positive pressure ventilation--IPPV) for acute severe asthma in a district general hospital during 1974-83. Thirty two patients required IPPV on 34 occasions. Complications included pneumothorax in six (18%) patients, chest infection in 12 (35%) patients, pulmonary collapse in three (9%) patients, hypotension at induction of IPPV in 12 (35%), and gastrointestinal bleeding in three (9%). Three (9%) patients died. Therapeutic bronchial lavage was performed in 19 patients. The procedure produced a rise in effective static compliance from a mean of 17 (SD 6) ml/cm H2O to 24 (9) ml/cm H2O at four hours. Bronchial lavage was associated with a significant excess of respiratory infections. A feature common to most patients was undertreatment before admission to hospital.
Combination therapy with thymosin ?1 and interferon for the treatment of chronic hepatitis C infection: A randomized, placebo-controlled double-blind trial
Authors: Kenneth E. Sherman, Maria Sjogren, Robin L. Creager, Melissa A. Damiano, Stephen Freeman, Scot Lewey, Dirk Davis, Spencer Root, Frederick L. Weber, Kamal G. Ishak, Zachary D. Goodman
Journal: Hepatology (1998)

Hepatitis C is a major cause of liver disease leading to cirrhosis. Although interferon (IFN) is the only approved therapy, treatment is characterized by low response rates and dose-limiting side effects. We evaluated the addition of thymosin α1 (TA1), an immunomodulatory peptide, to the standard treatment regimen for hepatitis C to determine if combination therapy shows biological activity using outcome measures including normalization of alanine aminotransferase levels, histological activity, and viral load during treatment. We performed a randomized, double-blind, placebo-controlled trial to compare the biological activity of a combination TA1 and IFN with that seen for IFN alone in patients with chronic hepatitis C infection. One hundred nine patients were randomized for intention to treat and received 1.6 mg of TA1 subcutaneously twice weekly and 3 MU of IFN three times weekly; 3 MU of IFN three times weekly and placebo TA1; or placebo for both agents. All patients had chronic HCV infection with confirmation of chronic hepatitis on liver biopsy. Biochemical responders were followed up until alanine aminotransferase (ALT) levels became abnormal or for 26 weeks, and relapsers were retreated for 26 weeks in the same treatment arm. One hundred three patients completed treatment for 26 weeks, and six patients dropped out. The groups were similar with regard to sex, gender distribution, baseline histological activity index (HAI) score, risk factors, and viral titers. End-of-treatment biochemical response was seen in 37.1% of patients treated with combination therapy, 16.2% of patients treated with IFN alone, and 2.7% of untreated controls by intent-to-treat analysis (IFN/TA1 vs. IFN, χ 2 = 4.05, P = .04). HCV RNA clearance was seen in 37.1% of IFN/TA1-treated patients and 18.9% of IFN-treated subjects. Mean HCV RNA titers were significantly lower than baseline at weeks 8, 16, and 24 after drug initiation among patients treated with IFN/TA1 but not in the other treatment arms. Histological improvement, as evidenced by a decrease in HAI of more than two points, occurred in the combination therapy arm more frequently than in comparison groups. Cumulative sustained biochemical responses were 14.2% and 8.1% in the IFN/TA1 and IFN arms, respectively, based on an intention-to-treat model. The combination of TA1 and standard IFN treatment for chronic hepatitis C showed evidence of biological activity at the completion of treatment by biochemical, histological, and virological outcome measures. Further research involving longer duration and varied dosing is needed.
Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of Salmonella.
Authors: J E Schweinle, R A Ezekowitz, A J Tenner, M Kuhlman, K A Joiner
Journal: Journal of Clinical Investigation (1989)

The human mannose-binding protein (MBP) is a multimeric serum protein that is divided into three domains, a cysteine-rich NH2-terminal domain that stabilizes the collagen alpha helix of the second domain and a third COOH-terminal carbohydrate recognition domain. Previous studies have shown that both native and recombinant human MBP bind to wild-type virulent Salmonella montevideo that expresses a mannose-rich lipopolysaccharide. Interaction with MBP results in opsonization and killing by phagocytes. In this report we show that low concentration of MBP (less than 10 micrograms/ml) markedly enhance complement deposition via the alternative complement pathway on S. montevideo. Despite structural similarities between MBP and the C1q subcomponent of the first complement component, MBP did not restore classical pathway activity to C1q-deficient serum, nor did it activate C1s when added to a mixture of C1r and C1s. In the presence of MBP the C3 bound to S. montevideo during incubation in serum was in the form of C3b and iC3b at a ratio of 1:2. Presensitization of S. montevideo with MBP rendered this normally serum resistant organism susceptible to complement-mediated killing. These results emphasize that MBP and complement cooperate in first line defense of the nonimmune host.
New deal not satisfactory for cardiothoracic surgery
Authors: A Alkhulaifi, S M Allen, J R Anderson, V Argano, C Austin, C Barlow, S Barnard, D Barron, R Berrisford, S Billing, E Brackenbury, P C Braidley, B J M Bridgewater, N P Briffa, K Buchan, J Butler, A R J Cale, H M H Carr, F Ciulli, S Clark, G J Cooper, S Craig, M Danton, W C Dihimis, J Duffy, A Duncan, J Gaer, G Gibson, S C Griffin, R I R Hasan, D Hopkinson, P Hornick, S Hunter, L C H John, R Kanagaseay, J Kuo, S Langley, A J Levine, V Mcnamara, E E. Oakley, S K Ohri, P A O'Keefe, D O'Regan, G W Parry, V L Pathi, P Peters, B Prendergast, P D Ridley, A J Ritchie, J C Roxburgh, D A C Sharpe, A C De Souza, R Steyn, K K Tan, M Tolan, U H Trevidi, G M K Tsang, S Tsui, M J Underwood, M J Unsworth-White, R Uppal, C Van Doorn, D A Waller, N Weerasena, V Young
Journal: BMJ (1995)

EDITOR,--We are pleased to read that the junior doctors' conference endorsed a motion arguing that implementation of the new deal may jeopardise the training of some higher specialist trainees.1 All the enrolled higher surgical trainees in cardiothoracic surgery currently working in the United Kingdom strongly support …
Community pharmacists are increasingly supervising treatments
Authors: R. Scott, H. Mcnulty
Journal: BMJ (1996)

<h3>Background and aims:</h3> The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease (GORD), which remains elusive, was quantified. <h3>Methods:</h3> The population included 3669 subjects undergoing repeated upper endoscopy. Data were analysed using a three-state Markov model to estimate transition rates (according to the Los Angeles classification) regarding the natural course of the disease. Individual risk score together with the kinetic curve was derived by identifying significant factors responsible for the net force between progression and regression. <h3>Results:</h3> During three consecutive study periods, 12.2, 14.9 and 17.9% of subjects, respectively, progressed from non-erosive to erosive disease, whereas 42.5, 37.3 and 34.6%, respectively, regressed to the non-erosive stage. The annual transition rate from non-erosive to class A–B disease was 0.151 per person year (95% CI 0.136 to 0.165) and from class A–B to C–D was 0.079 per person year (95% CI 0.063 to 0.094). The regression rate from class A–B to non-erosive disease was 0.481 per person year (95% CI 0.425 to 0.536). Class C–D, however, appeared to be an absorbing state when not properly treated. Being male (relative risk (RR) 4.31; 95% CI 3.22 to 5.75), smoking (RR 1.20; 95% CI 1.03 to 1.39) or having metabolic syndrome (RR 1.75; 95% CI 1.29 to 2.38) independently increased the likelihood of progressing from a non-erosive to an erosive stage of disease and/or lowered the likelihood of disease regression. The short-term use of acid suppressants (RR 0.54; 95% CI 0.39 to 0.75) raised the likelihood of regression from erosive to non-erosive disease. <h3>Conclusions:</h3> Intraoesophageal damage is a dynamic and migratory process in which the metabolic syndrome is associated with accelerated progression to or attenuated regression from erosive states. These findings have important implications for the design of effective prevention and screening strategies.
A STRAIN OF MICROSPORUM AUDOUINI PRODUCING NUMEROUS MACROCONIDIA ON CULTURE
Authors: P. J. HARE
Journal: British Journal of Dermatology (1952)

Journal Article A STRAIN OF MICROSPORUM AUDOUINI PRODUCING NUMEROUS MACROCONIDIA ON CULTURE Get access P. J. HARE, M.B., B.S.Lond., M.R.C.P.Lond. P. J. HARE, M.B., B.S.Lond., M.R.C.P.Lond. University College Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 64, Issue 6, 1 June 1952, Pages 236–242, https://doi.org/10.1111/j.1365-2133.1952.tb15901.x Published: 01 June 1952
Public health will suffer if GP commissioning groups are too small or the specialty is consigned to junior posts in local councils
Authors: A. McGauran
Journal: BMJ (2010)

The United Kingdom’s leading professional body for public health specialists fears that the radical reforms outlined in the government’s NHS white paper could result in worse services.

The president of the Faculty of Public Health, Lindsey Davies, said that although the personal commitment of England’s health secretary, Andrew Lansley, to public health was “very encouraging, there are lots of ‘ifs’, ‘buts,’ and possible slips along the way.”

Introducing the faculty’s annual public health lecture and award ceremony in London on Wednesday 6 October, she said that the changes proposed in July’s Equity and Excellence: Liberating the NHS paper “could do a lot of good, but at the moment everything is very uncertain.”

The most important shift proposed in the white paper involves consortiums of general practices taking over …
Viability in human heart valves prepared for grafting
Authors: C. G. A. MCGREGOR, J. F. BRADLEY, J. OD. MCGEE, D. J. WHEATLEY
Journal: Cardiovascular Research (1976)

Viability of antibiotic sterilized and stored human heart valves obtained at routine necropsy was assessed by tissue culture and protein and collagen synthesis. Only three of 23 valves examined showed any evidence of viability, in striking contrast to earlier work on canine valves obtained under optimal conditions. These findings justify doubts regarding pre-implantation viability in human heart valves prepared for grafting.
From a Retired Member.
Authors: J. L. Swett
Journal: JAMA (1896)

Newport, N. H., Jan. 28, 1896. <h3>To the Editor:</h3> —Your letter with sample copy of theJournalare received. Many thanks for the remembrance. In the success of theAmerican Medical Associationand its publications I have felt a deep interest from the time of its organization in 1847. I have most of the annual reports and<i>all</i>the volumes of theJournaluntil July, 1891. During a severe and protracted sickness that spring and summer, through some misunderstanding, my membership fee was not sent and my name, as it was right it should be, was dropped from the subscription list. As delegate from our State society I attended the annual meeting in New York in 1864 and in San Francisco in 1871, and as a permanent member, in Boston and Washington, always finding the occasions full of pleasure, instruction and benefit. My interest in medical literature and science, and
Abstract 2424: Synergistic induction of apoptosis in human solid cancer cells by Lexatumumab and cisplatin in a caspase-dependent manner
Authors: Wu Xiuxian, Masashi Inui, Mikio Sugimoto, Yoshiyuki Kakehi
Journal: Cancer Research (2010)

Abstract Introduction and Objectives: Mapatumumab and Lexatumumab are human agonistic antibodies against TNF-related apoptosis-inducing ligand (TRAIL)-receptor 1 (TRAIL-R1) and TRAIL-R2, respectively, which induce apoptosis specifically in cancer cells. Here, we investigated whether chemotherapeutic agents enhance Mapatumumab- or Lexatumumab-mediated apoptosis against various solid cancer cells. Methods: Cytotoxicity and synergy was assessed by MTT and isobolograpic analyses, respectively. TRAIL-R2 expression was detected by real-time RT-PCR, flow cytometry, and Western blotting. Apoptosis was assessed by DNA Ladder and caspase assays. Results: Treatment of ACHN human renal cell carcinoma (RCC) cells with cisplatin combined with Mapatumumab did not overcome resistance to these agents. However, treatment with cisplatin in combination with Lexatumumab had a synergistic cytotoxicity. Synergy was also achieved in six primary RCC cell cultures. Lexatumumab and cisplatin also synergistically enhanced apoptosis. Pretreatment with cisplatin followed by Lexatumumab resulted in high cytotoxicity compare with the reverse sequence. Cisplatin significantly increased TRAIL-R2 expression at both mRNA and protein levels. Furthermore, the combination of Lexatumumab and cisplatin significantly enhanced caspase-8 activity, Bid cleavage, up-regulation of Bax, cytochrome c release, and caspase-9, caspase-6, and caspase-3 activities. Importantly, the activation of capase-8 was significantly abrogated by the specific inhibitors of caspase-9, caspase-6, and caspase-3. Furthermore, combination-induced cytotoxicity was significantly suppressed by DR5: Fc chimeric protein and the specific inhibitors of caspase-8, caspase-9, caspase-6, and caspase-3. Similar effect was observed in prostate cancer, bladder cancer, lung cancer, and cervical cancer cells. Conclusions: Cisplatin sensitizes solid cancer cells to Lexatumumab-induced apoptosis by potentiation of the extrinsic and intrinsic apoptotic pathways that lead to enhancement of caspase activation, particularly caspase-8. These results suggest that combination of cisplatin plus Lexatumumab is promising against solid cancers. 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 2424.
More than half of diabetic patients do not get recommended annual tests
Authors: P. Wilson
Journal: BMJ (2010)

A large proportion of patients in England and Wales with diabetes are not undergoing the regular checks recommended to monitor their condition, says a national audit of diabetes care. Younger patients are particularly likely to miss out.

In 2008-9 just a third of people with type 1 diabetes and half of those with type 2 diabetes receive all nine of the annual checks recommended by the National Institute for Health and Clinical Excellence (NICE), despite the fact that 90% of patients with diabetes were seen by their healthcare team during the year.

The figures, from the national diabetes audit, represent an improvement on previous years—notably in comparison with the 11% of patients who received all nine tests in 2003-4, when auditing began. However, gradual improvement in monitoring has failed …
Case 22-1961
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. Kibbee
Journal: New England Journal of Medicine (1961)

Presentation of Case A fifty-two-year-old woman was admitted to the hospital because of tracheal obstruction. Nine months previously she noticed dyspnea and wheezing when walking during cold weather. Three months later severe coughing developed, with dyspnea and the production of yellowish sputum that was occasionally blood streaked. During  paroxysm of coughing  piece of tissue was coughed up, with marked relief of the dyspnea. Histologic examination revealed a wedge of trachea or bronchus showing inflammation, ulceration and  malignant epithelial tumor. Subsequently, she experienced severe laryngeal stridor and wheezing that improved with epinephrine therapy. Laryngoscopic examination showed acute inflammation. . . .
Prognostic Factors in Lung Cancer
Authors: Jin S. Lee, Waun K. Hong
Journal: New England Journal of Medicine (1992)

Non—small-cell lung cancer, which accounts for approximately 75 percent of the cases of lung cancer in the United States, represents a heterogeneous group of cancers, both biologically and histopathologically. Little progress has been made in their therapy over the past decades. In patients with this type of cancer, TNM stage (reflecting the size of the primary tumor, the involvement of regional lymph nodes, and the presence of metastases) is the most important prognostic factor, in that it largely determines treatment.1 , 2 If the patient has no distant metastases, the critical issue in staging is whether the tumor has invaded the mediastinal . . .
A Migratory Shingle Nail.
Authors: A. S. Condon
Journal: JAMA (1907)

Ogden, Utah, Feb. 25, 1907. <h3>To the Editor:</h3> —I have followed with interest the recent symposium inThe Journalrelating to the migrating needle, and now that about every one who cares to has told his story, I venture to obtrude with one that is authentic. A few years ago I was attending a convalescing patient for whom I ordered chicken broth. During the preparation of the chicken it was discovered that the liver, normal in every other way, was transfixed by a common nail some two or three inches long, usually called a shingle nail. It was not a modern wire nail, but one of the old-fashioned cut affairs. The nail was situated about the anatomical center of the liver and protruded equally on each side of that organ. The indications seemed to be that the nail had been in place a long time. The nail was of a
Time to Treatment With Intravenous Tissue Plasminogen Activator and Outcome From Acute Ischemic Stroke
Authors: Jeffrey L. Saver, Gregg C. Fonarow, Eric E. Smith, Mathew J. Reeves, Maria V. Grau-Sepulveda, Wenqin Pan, DaiWai M. Olson, Adrian F. Hernandez, Eric D. Peterson, Lee H. Schwamm
Journal: JAMA (2013)

NTRAVENOUS (IV) TISSUE-TYPE PLASminogen activator (tPA) is a treatment of proven benefit for select patients with acute ischemic stroke as long as 4.5 hours after onset. 1,2Available evidence suggests a strong influence of time to therapy on the magnitude of treatment benefit.In stroke animal models, time to reperfusion is a dominant determinant of final infarct volume. 3In human patients, imaging studies show the volume of irreversibly injured tissue in acute cerebral ischemia expands rapidly over time, typically consuming 2 million additional neurons per minute until reperfusion is achieved. 4Pooled data from IV tPA clinical trials indicate that therapeutic benefit of tPA is greatest when given very early after ischemic stroke
Letter: Granny-battering.
Authors: G R Burston
Journal: BMJ (1975)

scribing.Too mnany clinicians go into print on insufficient evidence when they have a single case.These are taken up and per- petuated by those who write articles on MAOIs as fact.A confused situation is being compounded by inaccurate and nmisleading evidence where factual and clear authoritative reporting is required for the guidance of both the doctor and the paticnt.-I am, etc.,
Verfolgung und Angst in Ihren Leib-Seelischen Auswirkungen
Authors: Ernest F. Muller
Journal: JAMA (1962)

The significance of this book lies in its establishment of a clearly defined opinion about the consequences of prolonged psychic traumatization. Based on the examination and observation of survivors exposed to Nazi persecution, it deals with this brutal impact upon the human personality and the permanent psychic injuries resulting therefrom.  The author describes how the inhuman experiment of the Third Reich created, quantitatively and qualitatively, situations of never-ending anxiety and horror for that small fraction who survived the exposure. This is recreated in short, succinctly described case histories of the anguish and suffering undergone by these people, both during and since their persecution.  To this background of facts in each case are added the clinical findings and opinions of the doctors who examined these survivors. Frequently, court decisions about compensation, based on this medico-psychiatric opinion, are noted. The reader obtains a clear picture of how different schools of thought have
Identification of Drugs
Authors: Joseph G. Caldwell, Alfred F. Shoman, Charles B. Hurst, William O. Robertson
Journal: JAMA (1964)

INITIATED BY HEFFERREN, the monumental task of making available to physicians and others an "Identification Guide for Solid Dosage Forms" reached culmination with the publication of the Dec 22, 1962, issue ofThe Journal.<sup>1</sup>Basing specificity on contrasts in physical characteristics, the Guide provides for the formation of a ten-digit code number for an unknown drug; the code number is then able to be matched with those of approximately 5,000 solid drug forms. When necessary, further differentiation can be accomplished by dimensional measurements (0.1 mm) in each of three planes, attention to imprints, etc. The question immediately posed itself, "<i>In the field</i>, will this method be as effective as intended?" We sought an answer in the following manner. <h3>Method</h3> Initially, 30 junior medical students and nine staff pediatricians ( group A ) were each confronted with three unknown medications—two tablets and one capsule. Each was also provided with a copy of