tbuckley/cabot-search huggingface dataset:
New Directions in Treatment Research for Personality Disorders: Effectiveness of Different Levels of Care
Authors: John S. Ogrodniczuk
Journal: Psychotherapy and Psychosomatics (2010)

Despite the many promising developments in the PD treatment research literature, several important issues remain inadequately addressed.Among these is the issue concerning the optimal level of care for the psychotherapeutic treatment of PDs.According to Gunderson et al.[14] , the level of care is a multi-dimensional construct that considers containment, intensity, structure, costs per day and duration.Generally speaking, levels of care can be organised hierarchically on the basis of these dimensions (except duration) into inpatient hospitalisation, partial hospitalisation/day treatment and outpatient treatment.The level of care has major ramifications in terms of resource allocation, which ultimately affects service delivery decisions.An additional, perhaps less well appreciated implication is the potential for stigma associated with different levels of care, which can influence patients' willingness to engage with health services.While the relevance of the level of care to the treatment of PDs has received considerable discussion in the literature, research on the matter has been lacking.This is likely owed to formidable methodological challenges, not the least of which is the unlikelihood of being able to randomly assign patients to different levels of care because of practical and ethical constraints.
Absence of FTL3 mutations in patients withJAK2V617F mutation negative essential thrombocythemia
Authors: Bruno C. Medeiros, Tong Zhang, Jeffrey H. Lipton, Suzanne Kamel‐Reid
Journal: American Journal of Hematology (2006)

A common point mutation in the JAK2 tyrosine kinase leads to constitutive hematopoietic growth factor receptor signaling and was recently described in many patients with myeloproliferative disorders (MPDs). However, this JAK2 mutation is present in only a subset (35-50%) of patients with essential thrombocythemia (ET). Thus, the proliferative signals responsible for MPDs in the absence of JAK2 mutations remain largely unknown. Despite intriguing pre-clinical data, where transgenic mice overexpressing FLT3-ITD developed a MPD resembling ET, none of the patient samples from ET patients who were JAK2(V617F)-negative demonstrated the presence of activating mutations in the FLT3 receptor.
Who says tobacco's bad for health? WHO!
Authors: Phil Gunby
Journal: JAMA (1986)

The World Health Organization (WHO) has come out swinging—against "the use of tobacco in all its forms"—in its first official action of 1986. WHO's Executive Board unanimously adopted a resolution condemning tobacco use as incompatible with the international goal of improved health for all the world's people by the turn of the century. Using WHO's primary, and almost only, means of leverage—attempts to influence world public opinion—the resolution also calls upon member nations that have not already done so to make certain "that nonsmokers receive effective protection, to which they are entitled, from involuntary exposure to tobacco smoke in enclosed public places, restaurants, transport, and places of work and entertainment." Discussion preceding the board's taking of the tougher stance included contentions that "the world pandemic caused by tobacco results in a million deaths each year and health authorities may be losing the fight they are waging against tobacco." Board members
The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies
Authors: Hongbin Ji, Danan Li, Liang Chen, Takeshi Shimamura, Susumu Kobayashi, Kate McNamara, Umar Mahmood, Albert Mitchell, Yangping Sun, Ruqayyah Al-Hashem, Lucian R. Chirieac, Robert Padera, Roderick T. Bronson, William Kim, Pasi A. Jänne, Geoffrey I. Shapiro, Daniel Tenen, Bruce E. Johnson, Ralph Weissleder, Norman E. Sharpless, Kwok-Kin Wong
Journal: Cancer Cell (2006)
Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice
Authors: Jakob Voelkl, Ioana Alesutan, Christina B. Leibrock, Leticia Quintanilla-Martinez, Volker Kuhn, Martina Feger, Sobuj Mia, Mohamed S.E. Ahmed, Kevin P. Rosenblatt, Makoto Kuro-o, Florian Lang
Journal: Journal of Clinical Investigation (2013)

Klotho is a potent regulator of 1,25-hydroxyvitamin D3 [1,25(OH)2D3] formation and calcium-phosphate metabolism. Klotho-hypomorphic mice (kl/kl mice) suffer from severe growth deficits, rapid aging, hyperphosphatemia, hyperaldosteronism, and extensive vascular and soft tissue calcification. Sequelae of klotho deficiency are similar to those of end-stage renal disease. We show here that the mineralocorticoid receptor antagonist spironolactone reduced vascular and soft tissue calcification and increased the life span of kl/kl mice, without significant effects on 1,25(OH)2D3, FGF23, calcium, and phosphate plasma concentrations. Spironolactone also reduced the expression of osteoinductive Pit1 and Tnfa mRNA, osteogenic transcription factors, and alkaline phosphatase (Alpl) in calcified tissues of kl/kl mice. In human aortic smooth muscle cells (HAoSMCs), aldosterone dose-dependently increased PIT1 mRNA expression, an effect paralleled by increased expression of osteogenic transcription factors and enhanced ALP activity. The effects of aldosterone were reversed by both spironolactone treatment and PIT1 silencing and were mitigated by FGF23 cotreatment in HAoSMCs. In conclusion, aldosterone contributes to vascular and soft tissue calcification, an effect due, at least in part, to stimulation of spironolactone-sensitive, PIT1-dependent osteoinductive signaling.
Persistence of Elevated Anti-Bet v 1 IgG4 Prior and during the Second Pollen Season after Allert Ultra-Fast Immunotherapy; Results from a Phase IIb Study Follow up
Authors: Christophe Reymond, Valerie Boand, Samantha Duc, Alexander Kettner, Gilles Della Corte, Francois Spertini
Journal: Journal of Allergy and Clinical Immunology (2015)
The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers
Authors: Dinis Pedro Calado, Yoshiteru Sasaki, Susana A Godinho, Alex Pellerin, Karl Köchert, Barry P Sleckman, Ignacio Moreno de Alborán, Martin Janz, Scott Rodig, Klaus Rajewsky
Journal: Nature Immunology (2012)
Senescence as a mode of tumor suppression.
Authors: R Sager
Journal: Environmental Health Perspectives (1991)

Two independent lines of experimental evidence are presented in support of the hypothesis that senescence is a normal mechanism of tumor suppression, a homeostatic device designed through evolution to limit cell proliferation irreversibly and thereby to protect the organism against cancer. One set of experiments uses normal human foreskin fibroblasts, transfected at early passage with SV40 DNA and subsequently infected with the K-ras virus. If the cells are immortal prior to infection, they become tumorigenic and make large tumors in nude mice, whereas if they are not immortal, though expressing SV40 T-antigen, they make tiny tumors that senesce in the test mouse after as many doublings as similar cells make in culture. This result demonstrates that immortalization is essential for progressive tumor growth in vivo. The second set of experiments demonstrate that normal human mammary epithelial cells can be immortalized by transfection with viral DNA from human papilloma virus 16 or 18, although these viruses have not been associated with breast cancer. The effective immortalization and other premalignant changes induced by human papilloma virus transfection are accompanied by chromosome changes that may contribute to the partially transformed phenotypes. None of the cloned or pooled transfectants have been tumorigenic in the nude mouse assay. Here, too, immortalization is experimentally separable from tumor-forming ability.
Abstract 670: Bis-nitrophenylphosphate (BNPP) but not phenylmethylsulfonyl fluoride (PMSF) inhibits the activation of the novel anti-cancer pro-drug CZ48
Authors: Constantine S.A Markides, Alexa P. Olszewski, Albert DeJesus, Kyle B. Vardeman, Lauren E. Moore, Dana M. Vardeman, Beppino C. Giovanella
Journal: Cancer Research (2011)

Abstract CZ48, the 20-O-propionate ester of Camptothecin (CPT), is a non-toxic prodrug of CPT first described by Cao et al. (1998). The propionate side-chain is enzymatically cleaved in target tissues. This gives rise to CPT, an inhibitor of Topoisomerase I, which then blocks cell division causing selective tumor toxicity. We have previously established the preferential activation of CZ48 in tumor tissues compared to normal tissues and an ultra sensitive assay to detect it (2009). The present studies explore the specifics of that activation in vitro using both cells in culture and surgically removed xenografted tumors from nude mice. DOY lung adenocarcinoma was grown subcutaneously in nude mice and then surgically excised, homogenized and serially centrifuged to produce specific subcellular fractions. The bulk of esterase activity was found to be concentrated in the cytosol, while the microsomal fraction showed minimal activity. All other fractions tested were below the limit of detection. HT-29 colon carcinoma cells were grown in culture in the presence and absence of varying concentrations of bis-nitrophenylphosphate (BNPP), a potent inhibitor of carboxylesterase and butyrylcholinesterase (BChE), in an attempt to find the highest possible non-toxic concentration to the cells. This concentration was then included during a 7-day IC50 determination for CZ48. In the presence of BNPP, the IC50 of CZ48 increased 4-fold from 181.4 nM to 710.8 nM. In vitro conversion of CZ48 to CPT by cytosolic fraction of a HT-29 tumor xenograft grown subcutaneously in nude mice was decreased by BNPP in a dose dependent manner. In contrast, the serine protease and carboxylesterase inhibitor phenylmethylsulfonyl fluoride (PMSF) and other esterase inhibitors did not affect the activation of CZ48. Purified butyrylcholinesterase and acetylcholinesterase (SigmaAldrich, St. Louis MO) did not show any capacity to activate CZ48. In conclusion, the enzymatic activation of CZ48 is not mediated by butyrylcholinesterase but by another cytosolic enzyme inhibitable by BNPP. These data constitute a significant step forward in unraveling the exact mechanism for the activation of CZ48. This will help design a pre-treatment assay to establish tumor sensitivity, as well as give us direction for designing new, more potent prodrugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 670. doi:10.1158/1538-7445.AM2011-670
Intrafamilial Transmission of Hepatitis C Virus Among the Population of an Endemic Area of Japan
Authors: Koya Nakashima
Journal: JAMA (1995)

To assess the role of intrafamilial transmission of hepatitis C virus (HCV) among general populations.Cross-sectional study in an HCV-endemic area of Japan.A total of 1122 residents (mean age, 41.7 years; range, 0 to 80 years), including 359 mother-child pairs and 234 pairs of spouses.Antibody to HCV (anti-HCV) was examined using second-generation anti-HCV testing by passive hemagglutination assay. Hepatitis C virus RNA was detected by polymerase chain reaction with primers deduced from the 5'-noncoding region and HCV genotypes by reaction with type-specific primers deduced from the HCV core gene.Prevalence of anti-HCV was 14.1% (158/1122), and HCV RNA was detected in 82.9% of those who tested positive for anti-HCV. Prevalence of anti-HCV increased with advancing age, but no anti-HCV was found among 312 persons younger than 20 years. Of the 53 children with anti-HCV-positive mothers, three were positive for anti-HCV, all were older than 20 years, and all had a history of surgical treatment. Hepatitis C virus RNA was found in one mother-child pair but with different HCV genotypes. Both spouses were positive for anti-HCV in 17 of 234 pairs. Of the 11 pairs of spouses in whom the HCV genotypes of both were determined, five had different HCV genotypes.While HCV is highly endemic in this area, neither vertical nor horizontal transmission between spouses seems to play an important role in its spread. The incidence of intrafamilial transmission of HCV seems to be low.
Screened Fibrinogen for Prophylaxis of Venous Thrombosis
Authors: N. C. Allan, R. A. Milne, C. V. Ruckley, J. K. Wood
Journal: BMJ (1971)

care, and administration of health services."It is, in short, medicine applied to a group rather than to an individual patient."The statement adds that it is hoped that the pro- visional Faculty will be in a position to re- ceive applications from those wishing to be- come founder members later in the year.Further announcements will be made. Monoamine-oxidase InhibitorsThe Pharmaceutical Society has printed an MAOI warning card and suggests that it should be issued whenever one of the fol- lowing drugs is dispensed: Iproniazid; Isocarboxazid; Mebanazine; Nialamide; Pargyline; Phenelzine; Pheniprazine; Phen- oxypropazine; Pivhydrazine; Tranylcypro- mine.The format of the card, which will be supplied to chemists and dispensing doctors, is as follows:TREATMENT CARD Carry this card with you at all times.Show it to any doctor who may treat you other than the doctor who pre- scribed this medicine, and to your dentist if you require dental treatment. INSTRUCTIONS TO PATIENTSPlease read carefully While taking this medicine and for 10 days after your treatment finishes you must observe the following simple instructions:1 Do not eat CHEESE. 2 Do not eat or drink BOVRIL, OXO, MARMITE or ANY SIMILAR MEAT OR YEAST EXTRACT. 3 Do not take any other MEDICINES (including tablets, capsules, nose drops, inhalations or suppositories) whether purchased by you or pre- viously prescribed by your doctor, without first consulting him.N B Coughandcoldcures,pain relievers, tonics and laxatives are medicines.Report any severe symptoms to your doctor and follow any other advice given by him.
Perinatal characteristics in relation to incidence of and mortality from prostate cancer
Authors: A. Ekbom, C.-c. Hsieh, L. Lipworth, A. Wolk, J. Ponten, H.-O. Adami, D. Trichopoulos
Journal: BMJ (1996)

To test the hypothesis that factors causing morbidity and mortality from prostate cancer may operate in utero.Matched case-control study of singleton men born between 1874 and 1946 at one hospital.Uppsala University Hospital.250 patients with prostate cancer and 691 controls, including 80 patients who died from prostate cancer and their 196 matched controls.Mother's age at menarche, parity, pre-eclampsia or eclampsia before delivery, age at delivery and socioeconomic status; case or control's birth length and weight, placental weight, prematurity derived from gestational age, and presence of jaundice.Both pre-eclampsia (odds ratio 0, 95% confidence interval 0 to 0.71) and prematurity (0.31, 0.09 to 1.04) were inversely associated with incidence of prostate cancer. Among subjects born full term, placental weight, birth weight, and ponderal index (weight/height 3) showed non-significant positive associations with prostate cancer incidence, and stronger associations with mortality.Prenatal exposures that are likely correlates of pregnancy hormones and other growth factors are important in prostate carcinogenesis and influence the natural course as well as the occurrence of this cancer.
The Rate of Lesions Found within Reach of Esophagogastroduodenoscopy during Push Enteroscopy Depends on the Type of Obscure Gastrointestinal Bleeding
Authors: L. F. Lara, R. S. Bloomfeld, B. C. Pineau
Journal: Endoscopy (2005)

Background and Study Aims: Many lesions found during push enteroscopy to evaluate obscure gastrointestinal bleeding are within the reach of standard endoscopes. The aim of this study was to determine whether the rate of proximal lesions varies in relation to the type of obscure bleeding that is present. Patients and Methods: A retrospective review of consecutive push enteroscopies carried out for obscure gastrointestinal bleeding between July 1996 and July 2000 was conducted. The patients were categorized into three groups: those with recurrent obscure/overt gastrointestinal bleeding; those with persistent obscure/overt gastrointestinal bleeding; and those with obscure/occult gastrointestinal bleeding. Results: A total of 63 patients (24 men, 39 women; mean age 69.8) were included. Push enteroscopy examinations were conducted for recurrent obscure/overt bleeding in 32 patients; for persistent obscure/overt bleeding in 12 patients; and for obscure/occult bleeding in 19 patients. The overall diagnostic yield of push enteroscopy was 47 % (15 of 32) in the group with recurrent obscure/overt bleeding; 66 % (eight of 12) in the group with persistent obscure/overt bleeding; and 63 % (12 of 19) in the group with obscure/occult bleeding. However, when lesions within the reach of standard esophagogastroduodenoscopy (EGD) were excluded, the yield of push enteroscopy was slightly higher in the group with recurrent obscure/overt bleeding (41 %) than in the groups with persistent obscure/overt bleeding (33 %) and obscure/occult bleeding (26 %). There were fewer lesions within the reach of EGD in the group with recurrent obscure/overt bleeding than in the groups with persistent obscure/overt bleeding (6 % vs. 33 %; P < 0.05) or obscure/occult bleeding (6 % vs. 37 %; P < 0.05). Conclusions: Patients undergoing push enteroscopy for recurrent obscure/overt bleeding were significantly less likely to have lesions within the reach of EGD than patients with persistent obscure/overt bleeding or obscure/occult bleeding. Patients in the latter two groups would be able to undergo a repeat EGD examination before more intense evaluation with push enteroscopy or capsule endoscopy.
Poliomyelitis in London in 1949
Authors: G. E. Breen, B. Benjamin
Journal: BMJ (1950)

0 43 1 84 85 81 0-51 0-28 0 35.._-:aatuatio eqaz Stuu.!uidt is measure at intervals thruhu th da. .Saturation equals 100.Humidity is measured at intervals throughout the day.t Rain collected in a gauge whose receiving surface is S in.(12-7 cm.) above the ground.The figures are the means of the sums of th.-weekly rainfall.
Diagnosing Marfan syndrome
Authors: M. Super
Journal: BMJ (1988)

ment of the polyethylene glenoid component with a metal keel will reduce late loosening but it is unlikely to do so if eccentric loading is the chief cause.Since the rotator cuff is so important in determining the outcome every effort, including arthrography and arthroscopy if necessary, ought to be made to determine its state before deciding to replace the joint.Those patients with an intact rotator cuff, or only a small defect, and painful deranged glenohumeral surfaces will get good pain relief and restoration of movement with an unconstrained arthroplasty done by an experienced surgeon.Such procedures are now carried out regularly in Britain.In patients in whom all else has failed the results are gratifying, although not as good as those of hip replacement: patients are usually left with residual stiffness and pain.Patients with arthritic joints and large cuff ruptures must await the development ofa currently impossible combination: a shoulder prosthesis that restores a stable glenohumeral fulcrum in such a way that intolerable loads are not placed on the interface.
Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study
Authors: Y. Kakeji, S. Yamaguchi, D. Yoshida, K. Tanoue, M. Ueda, A. Masunari, T. Utsunomiya, M. Imamura, H. Honda, Y. Maehara, M. Hashizume
Journal: Endoscopy (2006)

The Confocal Endomicroscopy System (Optiscan Pty Ltd. and Pentax Corp.) is a newly developed imaging tool that uses laser light and optical technology to visualize living tissue at the cellular level. Digital images of cells magnified 1000-fold appear in real time on a computer screen, which enables immediate detection of changes in cellular structure without the need for a biopsy. The aim of this study was to assess the features of the cellular architecture of cancerous tissue that can be used in the differential diagnosis of cancerous tissue and normal mucosa using this system's image-processing software.A total of 27 gastric cancers were examined ex vivo using confocal endomicroscopy. A fluorescent contrast agent, acriflavine, was applied topically to normal and to cancerous mucosa. In vivo imaging of the gastric mucosa after intravenous injection of fluorescein sodium was also performed in nine patients with gastritis or gastric cancer.The nuclear area in the ex vivo specimens was calculated using Scion Image software. The mean nuclear area of cancer cells was found to be significantly larger than that of normal cells in 18/27 gastric cancers (67 %). The mean nuclear area of the cancers tended to be larger than that of normal mucosa, especially in cases of differentiated adenocarcinoma. In more than half the cases, it was possible to diagnose malignancy automatically using confocal endomicroscopy and image-processing software without the need for biopsy and pathological examination. In vivo imaging of cancerous lesions showed irregularity in cellularity and vascularity.The ability of this imaging device to differentiate between normal tissue and cancerous tissues gives it potential value as a new screening tool for early detection of malignancy.
Doctors becoming managers.
Authors: M. A. Hunt, P. K. Walton
Journal: BMJ (1989)

a short intravenous tetracosactrin test disclosed a baseline plasma cortisol value of 410 nmol/l, increasing after 30 minutes to 590 nmol/l.Unfortu- natelv, the results were not immediatelv available and treatment was not started.Two days later another test was performed, showing further deterioration in adrenal function; the baseline plasma cortisol value was 470 nmolIl, increasing to 490 nmol/l after 30 minutes.Replacement treat- ment was started, and cardiovascular stability returned.We therefore suggest that in patients with septicaemia adrenal insufficiency should be sus- pected and a short intravenous tetracosactrin test performed.Treatment may need to be started before the results become available.When these are available the decision to continue treatment or not should be based on the increase in plasma cortisol concentration in response to tetracosactrin rather than its basal concentration.A peak plasma cortisol concentration of >400 nmolI may indicate a normal response in an outpatient but in a critically ill patient the "normal" basal concentration mav be much higher, at 550-1500 nmol/l.An increase in plasma cortisol concentration in response to tetracosactrin indicates that some adrenocortical response remains; no increase mav indicate a relative insufficiency.
Australia to investigate accusation of racism in accreditation of surgeons
Authors: C. Zinn
Journal: BMJ (1999)

Australia's watchdog organisation for national competitions will investigate allegations of a racist “closed shop” among the Royal Australasian College of Surgeons after a report called for a fairer system of accreditation for doctors trained overseas.

The Australian Competition and Consumer Commission is looking into the case of an Indian born fellow of the Royal College of Surgeons who was told he would have to train further before being allowed to continue to practise in …