tbuckley/cabot-search huggingface dataset:
Rising mortality from cryptogenic fibrosing alveolitis.
Authors: I Johnston, J Britton, W Kinnear, R Logan
Journal: BMJ (1990)

To determine the pattern of mortality ascribed to cryptogenic fibrosing alveolitis and to identify factors that might be important in the aetiology of the disease; and to assess the validity of death certification of the disease.A retrospective examination of mortality ascribed to cryptogenic fibrosing alveolitis in England and Wales between 1979 and 1988 with analysis, by multiple logistic regression, of independent effects of age, sex, region of residence, and social class as indicated by occupation on data for 1979-87; also a retrospective review of hospital records of patients certified as having died of cryptogenic fibrosing alveolitis in Nottingham and of the certified cause of death of patients known to have had the disease.Time trends in mortality nationally; effects on mortality of age, sex, and region of residence; validity of death certification in Nottingham.The annual number of deaths ascribed to cryptogenic fibrosing alveolitis doubled from 336 in 1979 to 702 in 1988, the increase occurring mainly at ages over 65. Mortality standardised for age for both sexes likewise increased steadily over the period. Deaths due to cryptogenic fibrosing alveolitis were commoner in men (odds ratio 2.24, 95% confidence interval 2.11 to 2.33) and increased substantially with age, being 7.84 (7.24 to 8.49) times higher in subjects aged much greater than 75 than those aged 45-64. Odds ratios of death due to cryptogenic fibrosing alveolitis adjusted for age and sex were increased in the traditionally industrialised central areas of England and Wales (p less than 0.02, maximum odds ratio between regions 1.25), but no significant increase in odds of death was found for manual occupations. Of 23 people whose deaths were registered in Nottingham as having been due to cryptogenic fibrosing alveolitis, 19 were ascertained from clinical records to have had the disease. Only 17 of 45 patients known to have had cryptogenic fibrosing alveolitis in life were recorded as having died from the disease.The diagnostic accuracy of death certification of cryptogenic fibrosing alveolitis is high, but the number of deaths recorded as being due to the disease may underestimate the number of patients dying with the disease by up to half. Mortality due to the disease is increasing, and the male predominance and regional differences in mortality suggest that environmental factors are important in its aetiology.
RUPTURE OF CESAREAN SCAR DURING PREGNANCY: REPORT OF A CASE
Authors: Carl R. Howson
Journal: JAMA (1918)

The patient was a Mexican woman, aged 24, and had been pregnant seven months. Nine months previously she had been delivered by cesarean section, and made an uneventful recovery, with the exception of a slight superficial infection in the abdominal wound. I was called to see her on a Saturday evening. About 2 p. m. the previous day, while at stool, she had been seized with pain in the abdomen of such severity that she was unable to move. Her physician was called, and finding her apparently in good condition she was put to bed and a mild anodyne administered. About midnight the pain recurred in paroxysms of great severity, and her physician was again sent for. He advised immediate removal to a hospital for laparotomy, but the advice was declined. She was catheterized at this time. The next forenoon he called, and again urged her removal to the hospital,
Properties of a subpopulation of T cells bearing histamine receptors.
Authors: M Plaut, L M Lichtenstein, C S Henney
Journal: Journal of Clinical Investigation (1975)

C57BL/6 mice immunized i.p. with alloantigen (P815 mastocytoma cells) develop cytolytically active thymus-derived (T) splenic lymphocytes. The definition of specific histamine receptor sites on effector T cells has been studied by measuring the in vitro effects of the hormone on cytolytic activity. Histamine was found to inhibit cytolysis reversibly and to increase lymphoid cell cyclic AMP levels. Both of these histamine activities were reversed by burimamide and metiamide; neither activity was affected by diphenhydramine or pyrilamine. These findings indicate that modulation of effector T cell activity by histamine is mediated only by one of the subtypes of tissue histamine receptors, designated a histamine-type 2 receptor. This receptor appears to be present on cytolytically active cells; there is no evidence for activation by histamine of auxiliary or "suppressor" cells. The estimated dissociation constant (KB) for the burimamide-receptor complex (9 times 10-minus 6 tm) and for the metiamide-receptor complex (8 times 10-minus 7 M) indicated that the histamine receptor on T cells is quite similar to histamine-type 2 receptors in other tissues. Cells bearing such receptors could not be isolated by passage through a column of histamine-coated tsepharose beads. The cytolytic activity of spleen cells taken from mice early (days 7-9) after immunization is virtually unaffected by histamine in vitro. In contrast, the activity of spleen cells taken from mice later in the immune response is progressively more susceptible to inhibition by histamine. After reaching a maximum at day 11, the spleen cell cytolytic activity falls in a pattern that parallels the increase in susceptibility to histamine. The susceptibility of effector T cells to histamine appears also to reflect their site of origin, for peritoneal exudate effector cells were found to be significantly less sensitive than spleen cells to inhibition by histamine. The progressive increase in inhibition by histamine apparently reflects the appearance of greater numbers of specific histamine-type 2 receptors, and is probably a general phenomenon, for spleen cells from A/J or C3H mice immunized with either P815 mastocytoma (H-2d) or EL-4 (H-2b) cells showed the same effect. However, the appearance of histamine receptors could be altered by prior immunization with an unrelated alloantigen: thus, when A/J mice are preimmunized with EL-4, a subsequent immunization with mastocytoma cells results in peak spleen anti-H-2d activity at day 9 instead of days 11-13, and the appearance of significant (greater than 40 percent) inhibition by histamine as early as day 8 instead of day 16. The physiological role of the histamine receptors is as yet undefined, though their unexpected rate of appearance on effector T cells, coincident with a decline in the number of lytically active cells in vivo, may be a significant hint that hormone receptors play a role in the control of T-cell proliferation.
What We Owe to Our Patients
Authors: Maurice Grossman
Journal: JAMA (1982)

With his report on confidentiality (p 2695), Weiss has performed a worthy service, if readers note but one finding: patients have faith in our professed principles of ethics. Their faith, however, may be greater than our practice warrants. Some of the difference in the responses of the patients, house staff, and students may be due to the semantics of the questionnaire. The use of<i>interesting</i>instead of<i>instructional</i>beclouds the issue and findings. The essence of the case cited by the author,<i>Doe v Roe</i>,<sup>1</sup>is that it is not only legitimate but essential that clinical material be published for the educational needs of the medical profession. However, endangering the patient's privacy is not warranted merely because the material might be interesting. This is in keeping with our medical ethics. We must recognize the legal position that the innate, constitutionally supported right to privacy belongs to the patient. In
HPMA copolymers containing doxorubicin bound by a proteolytically or hydrolytically cleavable bond: comparison of biological properties in vitro
Authors: M. Kovář, L. Kovář, V. Šubr, T. Etrych, K. Ulbrich, T. Mrkvan, J. Loucká, B. Říhová
Journal: Journal of Controlled Release (2004)
Clustering by health professional in individually randomised trials
Authors: Katherine J Lee, Simon G Thompson
Journal: BMJ (2005)

Patient outcomes in many randomised trials depend crucially on the health professional delivering the intervention, but the resulting clustering is rarely considered in the analysis Almost all trials that randomise individuals assume that the observed outcomes of participants are independent.The validity of this assumption is doubtful, however, in some situations.One example is when more than one health professional (such as surgeons, nurses, general practitioners, or therapists) delivers a non-pharmaceutical intervention to participants.Because health professionals may vary in their effectiveness, observations on participants treated by the same professional may be somewhat similar or clustered.Clustering of outcomes may also appear less obviously (such as in clustering by centre in a multicentre trial) or in a more dominant form (as in cluster randomised trials).In each of these situations the assumption of independence is violated, which means that standard statistical methods are invalid and may give misleading conclusions.The presence of clustering in a trial inflates standard errors and reduces the effective sample size, thus reducing the power of the trial.We examine the prevalence and importance of potential clustering in individually randomised trials and present an example of the effect it can have on the overall results and conclusions of a trial.References for trials and details of clustering and the statistical analysis are on bmj.com
Update on Therapy of Chronic Lymphocytic Leukemia
Authors: John G. Gribben, Susan O'Brien
Journal: Journal of Clinical Oncology (2011)

There have been tremendous advances in the treatment of chronic lymphocytic leukemia (CLL) over the past decade, with the goal of therapy no longer being just to palliate symptoms but now to achieve complete remission, eradicate minimal residual disease, and improve survival. During this period, there have also been major advances in identification of molecular factors associated with increased risk of progression. The clinical utility of these factors is being explored to determine whether we can identify groups of patients who should be treated earlier in their disease course and whether we can tailor therapy for groups of patients with specific molecular markers of disease. First-line chemoimmunotherapy approaches now offer prolonged survival, and there is a need to identify patients who are suitable candidates for allogeneic stem-cell transplantation that uses reduced-intensity conditioning regimens. The vast majority of CLL patients are either too old or do not have sufficiently high-risk disease to warrant these approaches, and effective therapies that can be tolerated by the more frail elderly patients with this disease are urgently needed. Numerous novel agents are being developed, and their role in the first-line treatment of frail patients or those who relapse after previous treatment is being explored in clinical trials.
Prevention of Typhoid Infection
Authors: Herbert A. Thomas
Journal: JAMA (1913)

To the Editor  —The sanitary closet-cans referred to by Dr. Charles T. Nesbitt in his article on  Control of Typhoid FeverThe Journal, Jan. 4, 1912, p. 6) may be easily obtained in localities where acetylene gas is used for general lighting purposes. The calcium carbid is supplied in airtight, screw-top, iron cans holding 100 pounds of carbid. These cans, when empty, make ideal closet-cans and cost nothing but the asking. I have used them in typhoid in a manner similar to that described by Dr. Nesbitt in his article, with the exception that they are not used the second time.
Decreased Body Potassium in Nondystrophic Relatives of Patients with Muscular Dystrophy
Authors: William H. Blahd, Benedict Cassen, Marianne Lederer
Journal: New England Journal of Medicine (1964)

EARLIER studies in patients with muscular dystrophy have shown a diminution in total body potassium that appeared to be correlated with the severity of muscle involvement.1 , 2 More recent studies have shown a similar depression in body potassium in some normal relatives of these patients.3 In addition, the usual physiologically constant relation between total body water and potassium, which is markedly altered in dystrophic subjects, is also slightly altered in unaffected relatives with decreased body potassium levels.4 MethodsStudies were performed on 47 patients with muscular dystrophy of the Duchenne or limb-girdle type, ranging in age from twelve to sixty-four years, . . .
1092-161 Ischemic mitral regurgitation is independent of papillary muscle dysfunction: Insights from tissue Doppler strain imaging in patients with inferior myocardial infarction
Authors: Takeshi Uemura, Yutaka Otsuji, Toshiro Kumanohoso, Keiko Yuge, Kenichi Nakashiki, Toshinori Yuasa, Akira Kisanuki, Sinichi Minagoe, Robert A Levine, Chuwa Tei
Journal: Journal of the American College of Cardiology (2004)
Abstract 1195: Erk activity promotes Notch-dependent HES1 expression in pancreatic cancer cells
Authors: Isabelle Tremblay, Jennifer Bintz, Marie-Josee Boucher
Journal: Cancer Research (2012)

Abstract The oncogene Ras is well-recognized for its involvement in tumorigenesis in part through activation of downstream pathways including the PI3K/Akt and Mek/Erk pathways. Recent studies have suggested that the ability of Ras to transform cells also depends on cooperation with the Notch signalling pathway. However, the molecular and cellular mechanisms involved in this cooperation remain largely unknown. The aim of this study was to evaluate whether specific activation of the Ras/Raf/Mek/Erk pathway impacts Notch-dependent signalling. METHODS. Experiments were done using the pancreatic cancer cells MIA PaCa-2 and BxPC-3. Both cell lines express endogenous levels of the activated Notch1 (NIC). To inhibit Mek/Erk activity, cells were treated with the Mek inhibitor U0126 (10uM). Activation of the Mek/Erk pathway was achieved by treatment with phorbol 12-myristate 13-acetate (PMA, 100nM). The hes1-luciferase reporter gene was used to evaluate Notch-dependent transcriptional activity. The gamma-secretase inhibitor DAPT (25µM) was used to inhibit Notch activation. RESULTS. 1- Treatment of pancreatic cancer cells with U0126 reduced the activity of the hes1-luciferase reporter gene to the same extent than treatment with the gamma-secretase inhibitor DAPT. 2- Combined treatment (U0126 + DAPT) did not result in an additive inhibition of hes1-luciferase activity suggesting a Notch-dependent impact of the Mek inhibitor on hes1 transcription. 3- Increased HES1 mRNA expression levels were observed following treatment with PMA, an effect prevented by addition of U0126. 4- Massive activation of the Notch receptors by treatment with EGTA promoted HES1 protein expression. 5- Interestingly, strong stimulation of Erk activity by PMA promoted the EGTA-induced HES1 protein expression. 6- Conversely, inhibition of Erk activity completely prevented both the EGTA-induced and EGTA+PMA-induced HES1 protein expression. CONCLUSION. Taken together, our results suggest that Erk activity promotes Notch-dependent transcriptional activity and consequently promotes the expression of Notch target genes such as HES1. 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 1195. doi:1538-7445.AM2012-1195
Improvement in exercise capacity and exercise hemodynamics 3 months after double-balloon, catheter balloon valvuloplasty treatment of patients with symptomatic mitral stenosis.
Authors: C R McKay, D T Kawanishi, A Kotlewski, K Parise, T Odom-Maryon, A Gonzalez, C L Reid, S H Rahimtoola
Journal: Circulation (1988)

Clinical status, exercise treadmill performance, and hemodynamics were determined in 24 patients with symptomatic mitral stenosis before catheter balloon valvuloplasty (CBV) and at 3 months follow-up. Hemodynamic determinations at rest showed that mitral CBV performed by the double-balloon technique resulted in significant immediate decreases in mean pulmonary arterial wedge pressure (28 +/- 7 to 16 +/- 5 mm Hg, p less than .01), mean pulmonary arterial pressure (41 +/- 11 to 33 +/- 10 mm Hg, p less than .05), and mitral valve gradient (16 +/- 7 to 6 +/- 3 mm Hg, p less than .01), and significant increases in cardiac output (4.3 +/- 1.1 to 5.0 +/- 1.4 liters/min, p less than .01). Mitral valve area increased from 1.0 +/- 0.3 to 2.2 +/- 0.7 cm2 (p less than .01). The mitral valve area was unchanged (2.0 +/- 0.7 cm2, p = NS) at 3 months. The lower pulmonary arterial wedge pressure, pulmonary arterial pressure, and mitral valve gradient persisted at 3 month follow-up catheterization. Clinical examinations showed that before CBV, 21 of 24 patients were in New York Heart Association functional class III or IV; 3 months after CBV, 22 patients were in class I or II. Before CBV, the mean exercise treadmill time was 5.9 +/- 3.2 min and it had increased to 9.8 +/- 2.9 min (p less than .01) by the 3 month follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjogren's syndrome and systemic lupus erythematosus
Authors: N. Pourmand, M. Wahren-Herlenius, I. Gunnarsson, E. Svenungsson, B. Lofstrom, Y. Ioannou, D. A Isenberg, C. G M Magnusson
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To investigate the occurrence of IgA autoantibodies to Ro 52 kDa, Ro 60 kDa and La antigen in serum of patients with primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). <h3>METHODS</h3> Recombinant Ro 52 kDa, Ro 60 kDa and La antigens were used to analyse autoantibodies in serum from 25 patients with pSS, 30 patients with SLE and 20 controls using a semiquantitative immunoblotting approach. <h3>RESULTS</h3> Among the patients with pSS, 21 (84%) had detectable IgA autoantibodies to Ro 52 kDa, 13 (52%) to Ro 60 kDa and 20 (80%) to La antigen. The corresponding results for the patients with SLE were 22 (73%), 14 (47%) and 20 (67%), respectively. No IgA autoantibodies against the three antigens were detected in 20 normal controls. A comparison of several clinical features with the titres of IgA antibodies to Ro 52 kDa, Ro 60 kDa and La, revealed a significant relation between IgA anti-Ro 52 and IgA anti-La to sicca (p&lt; 0.05). Semiquantitative data suggest that IgG is the dominating antibody to the three antigens followed by IgM &gt; IgA in both SLE and pSS patients. Specificity studies of IgA autoantibodies with different subfragments of Ro 52 kDa and Ro 60 kDa antigens showed that IgA antibodies did not differ from IgG and IgM in their recognition pattern. <h3>CONCLUSION</h3> These results suggest that besides IgM and IgG, IgA autoantibodies are also detected at high frequency in patients with pSS and SLE. Further studies are necessary to evaluate the contribution of these IgA autoantibodies to inflammation as well as their diagnostic value.
Gene Expression Analysis Proposes Alternative Pathways for the Mechanism by Which Celecoxib Selectively Inhibits the Growth of Transformed but not Normal Enterocytes
Authors: Eyal Sagiv, Uri Rozovski, Diana Kazanov, Eliezer Liberman, Nadir Arber
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Cyclooxygenase-2 inhibitor (celecoxib, Pfizer) is a promising chemopreventive agent, yet its long-term use may be limited due to increased cardiovascular toxicity. This study was aimed to identify genes and pathways involved in colorectal tumorigenesis and affected by celecoxib. Experimental Design: Normal rat enterocytes (IEC18 cells) and their Ras-transformed derivatives (R1) were exposed for 72 h or over 6 months to celecoxib and analyzed for gene expression pattern using Genechip (RG-U34). Cluster and pathway analyses were done using GeneSpring software and Gene Ontology database. Cyclin D1 was overexpressed in IEC18 cells using stable transfection; cell cycle and prostaglandin synthesis were assessed. Results: Five hundred thirty-eight genes were differentially expressed after transformation, and 70 and 126 genes, respectively, were affected by short and long treatments with celecoxib. Clusters of expression showed different expression in the transformed cells that revert to normal after treatment; they included Ras/Erk/Ral-B, Jagged2/Notch, calcineurin, lysyl-oxidase, etc. Cyclin D1 is up-regulated under the Ras pathway and is down-regulated by celecoxib. Thus, we showed that cyclin D1–transformed cells are resistant to inhibition by celecoxib. Celecoxib was also shown to work via cyclooxygenase-2 inhibition in transformed cells. Conclusions: Celecoxib selectively affects transformed and not normal enterocytes by targeting genes and pathways that are involved in the transformation. Thus, an alternative mechanism is proposed for the cancer-preventive role of celecoxib other than the classic mechanism of inhibiting prostaglandin synthesis, stressing mainly the role of cyclin D1. These data may help in the development of safer and more effective preventive drugs.
England sets up task force to hasten use of electronic records
Authors: Michael Cross
Journal: BMJ (2006)

Plans to create a shared electronic care record for every NHS patient in England are to be accelerated, despite auditors' reservations and a call from BMA members for GPs to consider boycotting the system.

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Lord Warner does not have “a flicker of doubt” that the records service will be in place by 2010

Credit: DAVID PARTNER/UPPA

Norman Warner, the minister responsible for reforming the NHS in England, announced the plans after the first independent audit of the four year old project was published last week.

In a long awaited report the National Audit Office calculated that the project, …

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BRONCHIAL ASTHMA COMPLICATING CARDIOVASCULAR DISEASE
Authors: JOSEPH HARKAVY
Journal: JAMA (1924)

Recent advances in our knowledge of human sensitization to foreign proteins have opened numerous avenues of approach to the studies of symptom-complexes such as asthma, vasomotor rhinitis and obscure gastrointestinal disorders, as well as cutaneous manifestations of the type of angioneurotic edema, urticaria, and eczema. That these conditions are not infrequently external evidences of cellular disturbances dependent on a varied protein intoxication is now generally conceded. That the mechanism of such disturbance differs, however, from the usual immunologic processes as seen in anaphylaxis and infections is evidenced by the attempts, unsuccessful, with few exceptions, to demonstrate experimentally antibody formation to the foreign proteins by the usual laboratory methods. These peculiar states of hypersensitiveness have been characterized as "allergy," a term first applied by von Pirquet,<sup>1</sup>and recently "atopy" by Coca and Cooke.<sup>2</sup> One of the most important of this group of diseases, asthma, has confused medical literature a