tbuckley/cabot-search huggingface dataset:
Polycythemia Vera: The Natural History of 1213 Patients Followed for 20 Years
Authors: None Gruppo Italiano Studio Policitemia*
Journal: Annals of Internal Medicine (1995)

To reassess the natural history of polycythemia vera and to obtain reliable estimates of both incidence of thrombosis and survival for use in defining the sample size for therapeutic clinical trials.Retrospective cohort study of patients with polycythemia who had been followed for 20 years.11 Italian hematology institutions.1213 patients with polycythemia vera, which was diagnosed according to criteria established by the Polycythemia Vera Study Group and commonly used in clinical practice.All-cause mortality, venous and arterial thrombosis, and hematologic and nonhematologic neoplastic disease. Myocardial infarction and stroke were classified as major thrombotic events, and venous and peripheral arterial thrombosis were considered minor thrombotic events. The number of patients who died and the number of those who had major thrombotic events (combined end point) were used as a comprehensive measure of the benefit-risk ratio associated with the use of myelosuppressive agents.634 fatal and nonfatal arterial and venous thromboses were recorded in 485 patients (41%); 36% of these episodes occurred during follow-up in 230 patients (19%), and 64% occurred either at presentation or before diagnosis. Thrombotic events occurred more frequently in the 2 years preceding diagnosis, suggesting a causal relation between the latent myeloproliferative disorder and the vascular event. The incidence of thrombosis during follow-up was 3.4%/y; older patients or those with a history of thrombosis had a higher risk for thrombosis. Overall mortality was 2.9/100 patients per year; thrombotic events and hematologic or nonhematologic cancers had similar effects on mortality. Patients receiving chemotherapy died three to four times more frequently than those not receiving chemotherapy. The increased risk for cancer in patients receiving myelosuppressive agents was seen approximately 6 years after diagnosis. In addition, the combined end point, computed as the sum of the hardest available events (death, nonfatal myocardial infarction, or stroke), suggests that myelosuppressive agents have an overall unfavorable effect.Cytoreduction favorably affects the incidence of thrombotic events, but aggressive treatment seems to be associated with increased risk for neoplasm. These results provide a basis for reevaluating the therapeutic strategy in patients with polycythemia vera and for estimating the size of clinical trials aimed at testing new therapeutic approaches.
Treatment of Anaemia
Authors: R. H. Girdwood
Journal: BMJ (1952)

<h3>Objective.</h3> The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Flare Group was established to develop an approach to identify and measure RA flares. An overview of our OMERACT 2014 plenary is provided. <h3>Methods.</h3> Feasibility and validity of flare domains endorsed at OMERACT 11 (2012) were described based on initial data from 3 international studies collected using a common set of questions specific to RA flare. Mean flare frequency, severity, and duration data were presented, and domain scores were compared by flare status to examine known-groups validity. Breakout groups provided input for stiffness, self-management, contextual factors, and measurement considerations. <h3>Results.</h3> Flare data from 501 patients in an observational study indicated 39% were in flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting &gt; 14 days. Pain, physical function, fatigue, participation, and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were obtained: r = 0.46 to 0.93. A combined definition (patient report of flare and 28-joint Disease Activity Score increase) was evaluated in 2 other trials, with similar results. Breakout groups debated specific measurement issues. <h3>Conclusion.</h3> These data contribute initial evidence of feasibility and content validation of the OMERACT RA Flare Core Domain Set. Our research agenda for OMERACT 2016 includes establishing duration/intensity criteria and developing criteria to identify RA flares using existing disease activity measures. Ongoing work will also address discordance between patient and physician ratings, facilitate application of flare criteria to clinical care, elucidate the role of self-management, and finalize recommendations for RA flare measurement.
Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+ stem cells from bone-marrow microenvironment
Authors: Koichi Hattori, Beate Heissig, Yan Wu, Sergio Dias, Rafael Tejada, Barbara Ferris, Daniel J. Hicklin, Zhenping Zhu, Peter Bohlen, Larry Witte, Jan Hendrikx, Neil R. Hackett, Ronald G. Crystal, Malcolm A.S. Moore, Zena Werb, David Lyden, Shahin Rafii
Journal: Nature Medicine (2002)
Effect of tPA on Regional Lung Perfusion in Unilobar Canine Pulmonary Thromboembolism
Authors: TAKESHI IKEDA, SEIKI NAKATANI, HIDENAO TAKATA, MIZUHO NOSAKA, AKITERU YOSHIKAWA, HIROTOMI TANAKA, SUSUMU YUKAWA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We investigated effects of tissue-type plasminogen activator (tPA) on regional pulmonary arterial hemodynamics in pulmonary thromboembolism (PTE) in a canine model of unilobar PTE. Ten beagle dogs were divided into two groups-tPA (n = 5) and control group (n = 5). In each dog an artificial blood circuit (ABC) consisting of a silicone tube and a cannulation-type electromagnetic blood flowmeter probe was placed at the left lower pulmonary artery. A unilobar PTE was induced by placing autologous clots into a metallic coil inside the ABC. The CO2 sampling tubes were positioned at the orifice of the left lower bronchus and the trachea, and the end-expiratory CO2 partial pressure (PET(CO2)) was measured. In the tPA group, blood flow at the left lower pulmonary artery (LL-flow) was improved to near baseline within approximately 30 min of receiving tPA, and PET(CO2) at the left lower bronchus (LL-PET(CO2)) increased in direct correlation with LL-flow. The hemodynamic improvement after tPA therapy correlated with the partial pressure of the regional pulmonary expiratory CO2. Moreover, it was suggested that changes in physiologic conditions in PTE were not determined by clot quantity alone.
Protein Kinase C α/β Inhibitor Go6976 Promotes Formation of Cell Junctions and Inhibits Invasion of Urinary Bladder Carcinoma Cells
Authors: Jussi Koivunen, Vesa Aaltonen, Sanna Koskela, Petri Lehenkari, Matti Laato, Juha Peltonen
Journal: Cancer Research (2004)

Abstract Changes in activation balance of different protein kinase C (PKC) isoenzymes have been linked to cancer development. The current study investigated the effect of different PKC inhibitors on cellular contacts in cultured high-grade urinary bladder carcinoma cells (5637 and T24). Exposure of the cells to isoenzyme-specific PKC inhibitors yielded variable results: Go6976, an inhibitor of PKCα and PKCβ isoenzymes, induced rapid clustering of cultured carcinoma cells and formation of an increased number of desmosomes and adherens junctions. Safingol, a PKCα inhibitor, had similar but less pronounced effects. In contrast, a PKCδ inhibitor, rottlerin, had an opposite effect on cell clustering and caused dissociation of cell junctions. A broad-spectrum PKC inhibitor bisindolylmaleimide I did not have any apparent effect on the morphology of the cultures or on the number of cell junctions. Additional studies with Go6976 demonstrated that inhibition of PKCα and β isoenzymes induced translocation of β1-integrin from the cell-matrix junctions and that β4-integrin was translocated to face the culture substratum. Go6976 was also highly effective in inhibiting migration of carcinoma cells and inhibited invasion through artificial basement membrane. Our results on urinary bladder carcinoma cells emphasize that Go6976 is a potential anticancer drug due to its effects on cell-cell and cell-matrix junctions, migration, and invasion. Furthermore, the results may be explained by changes in PKC activation balance promoted by inhibition of PKCα/β.
Incidence of advanced renal failure.
Authors: J Melia, R Beech, T Swan
Journal: BMJ (1991)

2-774), and thus couples who want to have children will continue to present.If a couple decide to have a child after they have been informed of the risks we advise the man to have a sperm count to rule out oligospermia and issue ovulation kits with advice to have unprotected intercourse only at the time of ovulation.As soon as pregnancy is confirmed the woman is referred to the consultant obstetrician in our hospital to register for antenatal care.We suggest a further HIV test at three months' gestation when termination might be an option, and we stress the need to use condoms throughout the pregnancy.The mother and baby are tested postnatally, and provided that the mother remains uninfected with HIV and condoms are used we advise that breast feeding is safe.Despite being aware of the risks couples will continue to have children.We believe that information should be provided to reduce these risks as far as possible.
Abstract 2379: Expression of truncated HER2 receptor in circulating tumor cells (CTCs) of breast cancer patients
Authors: Galaktia Kallergi, Dimitris Nasias, Maria A. Papadaki, Dimitris Mavroudis, Vassilis Georgoulias, Sophia Agelaki
Journal: Cancer Research (2012)

Abstract Introduction: HER2 receptor is overexpressed in 15-25% of patients with breast cancer. In HER2 positive breast cancer the administration of trastuzumab has changed the outcome of disease. However, most patients will eventually develop resistance to trastuzumab. The presence of a truncated receptor with loss of the extracellular portion of HER2 (p95HER2) has been proposed as a potential mechanism of resistance. Preclinical and clinical data suggest that the expression of p95HER2 is associated with poor overall prognosis, resistance to trastuzumab and sensitivity to lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor. We have recently shown that approximately 50% of breast cancer patients express HER2 in their CTCs (Kallergi et al., 2007; Kallergi et al., 2008). The aim of the present study was to characterize, for the first time, the expression of p95HER2 in CTCs of breast cancer patients. Methods: Triple staining immunofluorescent (IF) experiments were performed in peripheral blood mononuclear cells (PBMC) cytospins of patients with early (n=24) and metastatic (n=33) breast cancer who were CK-19 mRNA-positive by real time PCR. Pancytokeratin A45-B/B3 antibody (as a marker of CK-positive cells) was coupled with antibodies against the extracellular and the intracellular domains of HER2. Slides were analysed with either confocal laser scanning microscopy or with the Ariol system. Results: Cytokeratin positive cells were identified in 17 (71%) out of 24 early and in 20 (61%) out of 33 metastatic patients. HER2 positive CTCs were identified in 53% of early and 50% of metastatic CTC-positive breast cancer patients. HER2-positive CTCs lacking the extracellular domain of the receptor (p95HER positive CTCs) were identified in 35% of metastatic and 12% of early breast cancer patients. Exclusively p95HER2 positive CTCs were detected in 12% of patients with metastatic but not in patients with early disease. Conclusions: These data suggest that the truncated p95HER2 receptor is expressed in CTCs of both early and metastatic breast cancer patients. This finding has important therapeutic implications and may explain the observed increased efficacy of the trastuzumab plus lapatinib combination in HER2 positive breast cancer. 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 2379. doi:1538-7445.AM2012-2379
Thrombophilia Testing, Recurrent Thrombosis, and Women’s Health
Authors: Gregory Piazza
Journal: Circulation (2014)

C ase Presentation 1: A 33-year-old previously healthy man presented with sudden-onset dyspnea and sharp right-sided chest pain.He had noted right leg edema and calf discomfort a week earlier.He denied recent trauma, surgery, or immobility.His mother had a history of postpartum deep vein thrombosis (DVT).On physical examination, he was tachycardic with a heart rate of 114 bpm, normotensive with a blood pressure of 102/76 mm Hg, and hypoxemic to 88% on room air.Contrast-enhanced chest computed tomogram demonstrated bilateral segmental pulmonary embolism.Right lower-extremity venous ultrasound documented femoral and popliteal DVT.Case Presentation 2: A 78-year-old woman with hypertension and obesity developed acute left leg edema and pain 2 days after open reduction and internal fixation of a right hip fracture.On physical examination, the patient had severe edema and tenderness of the left lower leg and thigh.Left lowerextremity venous ultrasound documented left common femoral, distal femoral, and popliteal DVT.
Autopsy Rates and Diagnosis
Authors: Joanne Lynn
Journal: JAMA (1999)

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Commentary on emergence of hepatitis B virus S gene mutants in patients experiencing HBsAg seroconversion after peginterferon therapy
Authors: Seyed Mohamad Jazayeri, Seyed Moayed Alavian
Journal: Hepatology (2011)

We read with interest the article titled "Emergence of hepatitis B virus S gene mutants in patients experiencing HBsAg seroconversion after peginterferon therapy" by Hsu and Yeh.1 In this study, the authors found different substitutions within and outside the "a" determinant. They further tested the reactivity of those mutations. However, variations in the hepatitis B virus (HBV) surface protein (HBs) have also been reported in chronic carriers who did not receive vaccine/drug, with a frequency of 11%2, 3 in spite of the presence of antibody to HBs (anti-HBs).3, 4 Due to the quasispecies nature of HBV, the finding of different variants in a viral pool by molecular cloning is not surprising. Further, the authors did not test the patient's samples before the treatment (or sequential samples during the study), and therefore, they cannot be sure those mutations arose after interferon therapy. We believe that the variants found in the study by Hsu et al. could have emerged during the natural chronic course of HBV infection, regardless of pegylated interferon (PEG-IFN) therapy. Although the immune modulatory effect of drugs on anti-HBs seroconversion cannot be ignored, the anti-HBs in these patients may be possibly directed against the epitopes outside the "a" determinant, such as d/y or w/r subtype determinants. It seems that the consequence of selection pressure posed by natural antibodies would be the emergence of immune escape mutations which no longer could be recognized by the host immune system. Interestingly, patients with both HBs antigen (HBsAg) and anti-HBs–positive have been reported in 10%-25% of chronic active, hepatitis B e antigen (HBeAg)-positive patients.5 In our study of HBsAg mutants in 310 chronic HBsAg treatment-naive patients, we found numerous point mutations in 11% within the surface protein. Overall, 32 amino acid substitutions were found in the "a" determinant. A portion of those patients experienced anti-HBs seroconversion, but yet were still positive for HBV DNA (unpublished data). Therefore, the data suggest that escape mutations could be induced by an immunological pressure exerted on the major hydrophilic region (within or upstream and downstream of the "a" determinant), even in patients who are found to be negative for serum HBsAg by use of the routine assay. Seyed Mohamad Jazayeri M.D., Ph.D.*, Seyed Moayed Alavian M.D. , * Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, Baqiyatallah University of Medical Sciences, Baqiyatallah Research Center for Gastroenterology and Liver Disease, Tehran, Iran.
Private hospitals should have to report same safety data as NHS does, think tank says
Authors: I. Torjesen
Journal: BMJ (2014)

UK private hospitals should be obliged to report patient safety incidents and information on their performance in the same way as NHS organisations do, the think tank the Centre for Health and the Public Interest has said.

In a new report the centre argues that the safety of private hospitals, which now generate 28% of their income from treating NHS patients, cannot be assessed and compared directly with that of NHS organisations without this information.1

The report, published on 20 August, said that figures obtained from the healthcare regulator the Care Quality Commission (CQC) showed that between October 2010 and April 2014 802 patients died unexpectedly and there were 921 serious injuries in private hospitals in England. 

Most private hospitals have no intensive care beds, and some have no dedicated resuscitation teams, so the NHS acts as a “safety net” for private hospitals, the report added. Each year around 6000 patients are admitted to the …
Nocardiosis
Authors: Herbert F. Hager, Anthony V. Migliaccio, Raymond M. Young
Journal: New England Journal of Medicine (1949)

IN 1888 Nocard1 described an acid-fast sporothrix, Actinomyces farcinicus, as the cause of farcies du boeuf, or bovine farcy. Eppinger,2 in 1891, reported an aerobic, gram-positive, acid-fast actinomyces as the etiologic agent in a man dying with cerebral abscesses and meningitis. Since then the species of actinomycetes having acid-fast properties has been known as Streptothrix eppingeri, S. asteroides, Oospora asteroides, Actinomyces asteroides, Nocardia gypsoides and more recently N. asteroides. The literature on infections caused by this organism is not voluminous and indicates that cases are not common. The diagnosis in the great majority of cases was made only at . . .
Arthritis in beta thalassaemia trait: clinical and pathological features.
Authors: B B Dorwart, H R Schumacher
Journal: Annals of the Rheumatic Diseases (1981)

A 33-year-old white female of English descent with beta thalassaemia trait developed painful recurring bilateral knee effusion at age 15 years. Trauma was denied. Synovial analyses revealed noninflammatory effusions with normal complement, no inclusions, and no crystals. Knee x-rays normal at ages 18 and 26, showed mild osteoarthritic changes at age 33. Laboratory tests for other known causes of arthritis were repeatedly normal or negative. Bone densitometry was below normal. Light microscopy of the synovial membrane showed no significant abnormalities and no iron deposition. Electron microscopic findings included multilamination of vascular basement membranes and large amounts of thin fibrils surrounding many connective tissue cells. Treatment with salicylates did not prevent recurrence of effusions, and quadriceps strengthening and joint rest were moderately successful in relieving pain. Intra-articular corticosteroids on 2 occasions were not helpful. Whether her knee arthritis is purely secondary to the para-articular bone thinning from the chronic marrow expansion remains to be determined.
THE BASIC SYMPTOMS OF SCHIZOPHRENIA
Authors: Max Levin
Journal: American Journal of Psychiatry (1931)

In fourteen schizophrenic patients, mostly young, studied in an out-patient clinic, 23 observations were made of the presence of Bleuler's "basic" symptoms. These observations are presented in detail. Consideration is given to two questions: (1) In the normal individual how does the associative faculty develop? Confronted with a child of a given age who shows evidence of an association disturbance, can we say whether this disturbance is normal or abnormal for that age-level? (2) Can we differentiate the faulty associations of schizophrenia from those seen in mental retardation?
Precursors of Premature Disease and Death
Authors: CAROLINE BEDELL THOMAS
Journal: Annals of Internal Medicine (1976)

The youthful habits and family attitudes of medical students who later developed or died from one of five disease states were different from those of healthy classmate controls to begin with. In medical school, the total disorder group had significantly more nervous tension, anxiety, and anger under stress, had more insomnia, smoked more cigarettes, and took alcoholic drinks more frequently. Individual disorder group means were significantly different from each other. The mental illness group showed the most nervous tension, depression, and anger under stress and the malignant tumor group the least. The malignant tumor group resembled the healthy control group in these respects. The suicide, mental illness, and malignant tumor groups had low mean scores for closeness to parents, while the hypertension and coronary occlusion group means were slightly higher than the control group mean. Thus psychologic differences in youth have predictive potential in regard to premature disease and death.
Measurement of Arterial Aging in Relation to Diabetes Mellitus
Authors: JOHN H. HUSTON, FRANCOIS M. ABBOUD
Journal: Circulation (1962)

The purpose of this study was to investigate the incidence of premature arterial aging in diabetes mellitus and to re-examine the relationship between this type of degenerative vascular change and the other features of the diabetic state. A sensitive method was used to measure changes in the elastic properties of large arteries. Twenty-nine of 50 diabetic patients had premature arterial aging. Sixty-two per cent of the patients, with abnormally high rigidity indices had retinopathy and 21 per cent had Kimmelstiel-Wilson's syndrome. The findings suggest that in diabetic patients premature arteriosclerosis is not necessarily secondary to peripheral occlusive angiopathy. The importance of the duration of diabetes in the development of premature arterial aging was demonstrated. An accelerated arteriosclerotic process may occur with late onset of diabetes. The relation between the metabolic and the vascular defects, was not clear cut. The possibility that the vascular anomalies of the diabetic trait might be inherited without the metabolic counterpart was suggested by the discovery of premature arterial aging in 11 of 50 nondiabetic subjects with a family history of diabetes.