tbuckley/cabot-search huggingface dataset:
HUMAN PROTHROMBIN: QUANTITATIVE STUDIES ON THE PLASMA LABILE FACTOR AND THE RESTORATIVE EFFECTS OF NORMAL, HYPOFI-BRINOGENEMIC, AND HEMOPHILIC PLASMA ON THE PROTHROMBIN OF STORED PLASMA 1
Authors: Benjamin Alexander, Andre De Vries, Eunice Addelson
Journal: Journal of Clinical Investigation (1949)

In 1943 Quick (1) reported on the multiple na- ture of plasma prothrombin.On the basis of his data, which have been repeatedly confirmed (2-4), he concluded that prothrombin consists of two essential factors combined with calcium.The two components, "prothrombin A" and "prothrombin B," had different properties.The former was labile in oxalated or citrated plasma stored at re- frigerator temperatures, not adsorbable by alumi- num hydroxide, fairly heat stable, and not reduced in dicumarolized blood.Its deterioration was said to account for the high prothrombin time of stored plasma."Prothrombin B," on the other hand, re- mained intact in refrigerated plasma, was re- moved by aluminum hydroxide, was labile at 600 C. for 15 minutes, and was decreased by the ad- ministration of dicumarol.More recently other entities were described which affect the conversion of prothrombin to thrombin by thromboplastin plus calcium (5-7).These are apparently distinct from both "prothrombin B" and the factor which deteriorates in stored plasma.The term "prothrombin A" is now reserved by Quick (5) for one of these substances, and the term "labile factor" for the moiety which is found wanting in stored plasma.Normal pro- thrombin activity, as determined by the one-stage method, requires the presence of adequate amounts of all these substances.Loomis and Seegers (4) found that the pro- thrombin activity of aged plasma could be restored remarkably by the addition of purified fibrinogen.Accordingly, they concluded that deterioration of fibrinogen accounts for lengthening of the pro- thrombin time in stored plasma and that "reactive
Outbreak of Paratyphoid in the Edinburgh Area
Authors: J. C. M. Sharp, P. P. Brown, G. Sangster
Journal: BMJ (1964)

From time to time outbreaks of paratyphoid infection have occurred in the United Kingdom, most of which in recent years have been attributable to imported food ingredients, especially frozen Chinese egg and desiccated coconut.Of the many phage types of Salmonella paratyphi B, the Taunton strain has been prominent, notably in Eastbourne, Southwark, Motherwell, and the Manchester area (Cockburn et al., 1951; Cameron, 1959; Young, 1960; Anderson, 1962).More recently similar out- breaks have occurred in East Anglia, Surrey, and Yorkshire (Brit.med. 7., 1963).In the early months of 1963 an extensive outbreak of para- typhoid B fever occurred in the Edinburgh area, caused primarily by infected bakery confectionery.The organism responsible was Saim.paratyphi B, phage type Taunton.
Effect of treatment of <i>Strongyloides</i> infection on HTLV‐1 expression in a patient with adult T‐cell leukemia
Authors: Lee Ratner, Christian Grant, Bevin Zimmerman, Joseph Fritz, Gary Weil, Alex Denes, Rama Suresh, Nancy Campbell, Steve Jacobson, Michael Lairmore
Journal: American Journal of Hematology (2007)

Abstract Human T‐cell leukemia virus type 1 (HTLV‐1) is associated with adult T‐cell leukemia–lymphoma (ATLL) in about 5% of infected individuals. Coinfection by Strongyloides stercoralis has been suggested to be a cofactor for development of ATLL. We describe a patient who presented with HTLV‐1‐associated chronic ATLL and Strongyloides infection. Studies of this patient's viral RNA levels demonstrated stimulation of HTLV‐1 replication by Strongyloides , which resolved with anti‐helminthic therapy. This case provides support for the hypothesis that Strongyloides is a cofactor for ATLL via T‐cell stimulation. Am. J. Hematol. 82:929–931, 2007. © 2007 Wiley‐Liss, Inc.
Blastic plasmacytoid dendritic cell neoplasm
Authors: Javier Munoz, Jatin Rana, Kedar Inamdar, David Nathanson, Nalini Janakiraman
Journal: American Journal of Hematology (2011)

Sixty-six-year-old female presented with left forearm soft tissue swelling for 2 months. An ultrasound of her left forearm showed a 6.5 cm × 1 cm × 3.6 cm soft tissue mass, which was also confirmed by magnetic resonance imaging (Panel A and B). A routine screening mammogram revealed a new 4 mm mass in her left breast. Subsequent left breast needle biopsy and left forearm fine needle aspiration favored an undifferentiated malignant neoplasm of hematolymphoid origin (Panel D) with positive CD4 (Panel E) and positive CD56 (Panel F) markers compatible with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Positron emission tomography (PET) scan showed increased uptake in the left forearm (Panel C), left breast, bilateral pleura, liver, spleen, portocaval lymph nodes, and omental caking. A bone marrow biopsy was negative for malignancy, and shortly thereafter the patient underwent induction therapy with cytarabine and idarubicin. Following progression of metastatic disease on PET scan, the patient received reinduction chemotherapy with mitoxantrone, etoposide, and cytarabine. BPDCN is a rare malignancy formerly recognized as CD4+/CD56+ hematodermic neoplasm and is suggested to have derived from plasmacytoid dendritic cells. It typically presents in middle-aged or elderly patients with skin or soft tissue involvement and concurrent disseminating disease carrying poor prognosis. BPDCN expresses CD4, CD56, CD123 (interleukin-3 receptor alpha chain), and BDCA-2 (blood dendritic cell antigen 2), whereas expression of TCL1 is helpful when the tissue displays weak expression of aforementioned markers. Treatment involves multiagent chemotherapy followed by subsequent stem cell transplantation for best outcomes. Unfortunately, our patient showed dismal response to chemotherapy, and the originally intended stem cell transplantation could not be instituted due to poor performance status. Panel A and B, magnetic resonance imaging of left forearm mass. Panel C, positron emission tomography showing increased uptake in the left fore arm. Panel D, Hematoxylin-eosin stain. Panel E, positive CD4. Panel F, positive CD56.
Will short-term TB therapy regimens work?
Authors: John Elliott
Journal: JAMA (1978)

Two new short-term therapy programs for tuberculosis (TB), based on twice-weekly chemotherapy with isoniazid and rifampin, have been developed recently by the Public Health Service (PHS) and by the Arkansas State Department of Health. Although similar in design and intent, the two programs have had substantially different results. While current TB therapy programs in this country have proved acceptable, the promise of quicker results, higher patient compliance with the treatment protocol, curtailed side effects, and much greater cost-effectiveness has inspired the experimental short-course regimens. The Arkansas program, which uses nurse practitioners in the field to ensure that patients comply with the prescribed therapy, has been highly successful. The PHS program, relying for the most part on voluntary compliance, has been less so. Both therapy regimens use isoniazid and rifampin at similar doses. The Arkansas program calls for initial treatment with isoniazid, 300 mg, and rifampin, 600 mg, in single daily
Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study
Authors: Esteban Martínez, Amanda Mocroft, Miguel A García-Viejo, José B Pérez-Cuevas, José L Blanco, José Mallolas, Luis Bianchi, Ignacio Conget, Jordi Blanch, Andrew Phillips, José M Gatell
Journal: The Lancet (2001)
Raised plasma cholesterol precursors in patients with gut resections.
Authors: M A Farkkila, R S Tilvis, T A Miettinen
Journal: Gut (1988)

Cholesterol synthesis, faecal bile acids and neutral sterols, and plasma squalene and free and esterified cholesterol precursor sterols concentrations were studied in patients with previous ileal resection (n = 30) or jejunoileal bypass (n = 9) to elucidate the responses of different cholesterol precursors to enhanced cholesterol synthesis induced by cholesterol and bile acid malabsorption. A subgroup of seven resection patients without fat and bile acid malabsorption served as controls. Of the resection patients, eight had a pure bile acid malabsorption and 15 a combination of fat, bile acid, and modest cholesterol malabsorption. In the patients with jejunoileal bypass, cholesterol and fat absorption was greatly decreased in addition to bile acid malabsorption. The overall cholesterol synthesis was associated with proportionately increased plasma contents of free (and, less consistently, esterified) methyl sterols, the most marked increase, up to 18 times, being recorded for free and esterified lathosterols. The concentrations of the precursor sterols were similarly increased in the subjects with bile acid and cholesterol malabsorption, the two lathosterols showing the highest correlations with the overall cholesterol synthesis (r = 0.820-0.941). In the subjects with jejunoileal bypass cholesterol malabsorption effectively regulated cholesterol synthesis and the precursor levels. Gut exclusions large enough to cause cholesterol and/or bile acid malabsorption activate cholesterol synthesis leading to a proportional elevation in the plasma concentrations of cholesterol precursors, especially in those of lathosterols and free methyl sterols. Determination of the plasma concentration of total lathosterol by a single gas-chromatographic run is a suitable method for rapid screening of clinically significant cholesterol and bile acid malabsorption.
Rates of Adverse Events Associated With Male Circumcision in US Medical Settings, 2001 to 2010
Authors: Charbel El Bcheraoui, Xinjian Zhang, Christopher S. Cooper, Charles E. Rose, Peter H. Kilmarx, Robert T. Chen
Journal: JAMA Pediatrics (2014)

Approximately 1.4 million male circumcisions (MCs) are performed annually in US medical settings. However, population-based estimates of MC-associated adverse events (AEs) are lacking.To estimate the incidence rate of MC-associated AEs and to assess whether AE rates differed by age at circumcision.We selected 41 possible MC AEs based on a literature review and on medical billing codes. We estimated a likely risk window for the incidence calculation for each MC AE based on pathogenesis. We used 2001 to 2010 data from SDI Health, a large administrative claims data set, to conduct a retrospective cohort study.SDI Health provided administrative claims data from inpatient and outpatient US medical settings.For each AE, we calculated the incidence per million MCs. We compared the incidence risk ratio and the incidence rate difference for circumcised vs uncircumcised newborn males and for males circumcised at younger than 1 year, age 1 to 9 years, or 10 years or older. An AE was considered probably related to MC if the incidence risk ratio significantly exceeded 1 at P < .05 or occurred only in circumcised males.Records were available for 1,400,920 circumcised males, 93.3% as newborns. Of 41 possible MC AEs, 16 (39.0%) were probable. The incidence of total MC AEs was slightly less than 0.5%. Rates of potentially serious MC AEs ranged from 0.76 (95% CI, 0.10-5.43) per million MCs for stricture of male genital organs to 703.23 (95% CI, 659.22-750.18) per million MCs for repair of incomplete circumcision. Compared with boys circumcised at younger than 1 year, the incidences of probable AEs were approximately 20-fold and 10-fold greater for males circumcised at age 1 to 9 years and at 10 years or older, respectively.Male circumcision had a low incidence of AEs overall, especially if the procedure was performed during the first year of life, but rose 10-fold to 20-fold when performed after infancy.
Liver resection and needle liver biopsy cause hematogenous dissemination of liver cells
Authors: Malek Louha, Jérome Nicolet, Herve Zylberberg, Abdelmajid Sabile, Corinne Vons, Giovanna Vona, Karine Poussin, Monique Tournebize, Frédérique Capron, Stanislas Pol, Dominique Franco, Bernard Lacour, Christian Bréchot, Patrizia Paterlini-Bréchot
Journal: Hepatology (1999)

We have investigated whether liver resection and needle liver biopsy cause dissemination of liver cells into peripheral blood circulation, using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay targeted against alpha-fetoprotein (AFP) mRNA. Twelve patients with and 16 without primary liver cancer (PLC) undergoing liver resection were tested before skin incision, after liver mobilization, after hepatic parenchyma transection, after abdominal wall suture, and 4 days after surgery. Two patients with and 20 without PLC were tested before, 20 minutes after, and 24 hours after needle liver biopsy. Six of 14 patients with and 0 of 36 patients without PLC scored positive before intervention (P <.001). Liver cell spreading was induced at different times after surgery and liver biopsy in 14 of 14 patients with but also 23 of 36 without PLC (P <.05). We conclude that liver resection and needle liver biopsy induce release of cells from the liver, which are not necessarily liver tumor cells, into the peripheral blood circulation. This may be, however, an important mechanism of liver cancer cell dissemination deserving further investigations.
Somatic mutations, acetylator status, and prognosis in colorectal cancer
Authors: J E Hardingham, W J Butler, D Roder, A Dobrovic, R B Dymock, R E Sage, I C Roberts-Thomson
Journal: Gut (1998)

Somatic mutations in K-ras and TP53 may be associated with both acetylator status and prognosis in colorectal cancer.To determine whether cancers with somatic mutations are more frequent in fast acetylators and whether mutations or acetylator status influence prognosis after colorectal surgery.One hundred consecutive subjects undergoing elective surgery for colorectal cancer.Acetylator status was determined by polymerase chain reaction (PCR) genotyping for polymorphism in the N-acetyltransferase 2 (NAT2) gene. Mutations in K-ras (codon 12) and TP53 were determined by PCR analysis using restriction enzyme digestion and single strand conformation polymorphism respectively. Survival from colorectal cancer for up to five years after diagnosis was analysed using the Kaplan-Meier product limit estimator. Cox proportional hazards regression was used to compare survival rates after adjusting for tumour stage.Mutations in K-ras and TP53 were independent of acetylator status. By log rank test, survival was significantly reduced in subjects with TP53 mutations (p = 0.003) but was not significantly related to acetylator status or the presence of K-ras mutations. After adjustment for tumour stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality (95% confidence interval 1.5 to 11.6) when compared with that of a TP53 negative reference group.The presence of both TP53 and K-ras mutations in colorectal tumours is an adverse prognostic marker which is independent of tumour stage.
Abstract 5049: Targeting the Notch and mTOR pathways in diffuse intrinsic pontine glioma.
Authors: Marianne Hutt, Wendy Goldstein, Javad Nazarian, Antoinette Price, Kah Jing Lim, Katherine Warren, Howard Chang, Charles Eberhart, Eric Raabe
Journal: Cancer Research (2013)

Abstract Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric brain tumor which is known to have frequent alteration of mTOR signaling. Analysis of DIPG tissue obtained through the Mid-Atlantic DIPG Consortium (MADC) also shows high level activation of Notch pathway effectors HES4 and HES5. We have established JHH DIPG1, a human DIPG xenograft and neurosphere cell line from a rapid autopsy specimen obtained through the MADC. Notch 1 and 3 and Notch downstream effectors, Hes1, Hes5 and Hey1, are highly expressed in JHH DIPG1 and a second DIPG line, SU DIPG1. These DIPG cell lines also express high level phospho-S6 and phospho-AKT 473, indicating activation of TORC1 and TORC2. Notch and mTOR pathway signaling is equal to or exceeding that observed in glioblastoma neurosphere cell lines. Notch targeting using a gamma-secretase inhibitor leads to a dose-dependent reduction in cell proliferation of up to 30% (p=0.05) as well as inhibition of phospho-AKT 473, suggesting that inhibition of the NOTCH pathway targets TORC2 complexes. BrdU incorporation also showed that treatment of DIPG cell lines with a TORC1 inhibitor also has up to a 60% attenuation of cell proliferation (p&amp;lt;0.005) in treated DIPG cells compared to non-treated cells and a dose-dependent reduction in phospho-S6, with concomitant upregulation of phospho-AKT 473 indicating TORC2 activation. Dual TORC1 and TORC2 inhibition by combining a rapalog and a gamma-secretase inhibitor may prove to be synergistic in DIPG. Simultaneous treatment with a rapalog and gamma-secretase inhibition suppresses TORC1 and TORC2, as measured by western blot. We are currently investigating the possible mechanism of action of these drugs in DIPG. Our laboratory is investigating additional metabolic inhibitors that can be used with TORC1 and TORC2 inhibitors to further improve treatment options for DIPG. We are currently exploring the role of the Notch and mTOR pathways in DIPG in pre-clinical studies in mice, with the goal of moving targeted inhibitors into clinical trials for these currently highly lethal tumors. Citation Format: Marianne Hutt, Wendy Goldstein, Javad Nazarian, Antoinette Price, Kah Jing Lim, Katherine Warren, Howard Chang, Charles Eberhart, Eric Raabe. Targeting the Notch and mTOR pathways in diffuse intrinsic pontine glioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5049. doi:10.1158/1538-7445.AM2013-5049
Short course of cognitive behavioural therapy may reduce health anxiety, say researchers
Authors: J. Wise
Journal: BMJ (2013)

A short course of cognitive behavioural therapy delivered by nurses with minimal training would be an effective and relatively cheap way to reduce health anxiety in general medical clinics, researchers claim.

Health anxiety or hypochondriasis places a substantial burden on health services because it leads to multiple consultations and investigations. Cognitive behavioural therapy is known to be an effective treatment for other anxiety disorders, but there are shortages of specialist therapists and long waiting lists for treatment.

The Cognitive Behaviour Therapy for Health Anxiety in Medical Patients (CHAMP) study randomised 445 people with abnormal health anxiety who were attending gastroenterological, neurological, and respiratory medicine clinics in …
Insulin as a First-Line Therapy in Type 2 Diabetes
Authors: Eberhard Standl, Oliver Schnell
Journal: Diabetes Care (2008)

Because a tidal wave of type 2 diabetes is presently rolling on a global scale, owing to the ever-increasing prevalence of obesity along with overnutrition, increasing physical inactivity, and aging populations worldwide, the debate is still ongoing over the appropriate first-line therapy. Recently, the International Diabetes Federation and the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) suggested distinct treatment algorithms (Fig. 1) (1), which have sparked the discussion even further, although there is strong agreement that weight-regulating nutrition and a prudent lifestyle are the cornerstones of any treatment. Here, the pro and con discussion explores the use of insulin versus sulfonylureas as first-line pharmacotherapy.



 Figure 1—  
ADA/EASD consensus: management of hyperglycemia in type 2 diabetes (1).



### Evidence base

The landmark UK Prospective Diabetes Study (UKPDS) has published evidence-based outcome results comparing the randomized addition of insulin or sulfonylurea treatment (with glibenclamide) to lifestyle therapy after diagnosis of type 2 diabetes (2). To make a long story short, no difference between these two treatment options was observed. Both gave a similar degree of (yet overall unsatisfactory) metabolic control long term and both reduced microvascular complications significantly, but failed to reduce macrovascular end points. Both therapies were burdened by significant weight gain and the risk of serious hypoglycemic episodes (2). These downsides appeared to be more marked with insulin therapy. So, based on these data, very little evidence exists that first-line insulin therapy is superior to sulfonylurea treatment, since no other long-term studies are available at present.

### Limitations of present information

Insulin therapy in the UKPDS was not very well structured and was mainly based on long-acting insulin, which more or less has been abandoned. Newer concepts of insulin therapy have not been tested, e.g., combination therapies with intermediate-acting insulins or insulin analogs with flat action profile together with oral agents, in particular with metformin. …
Lecture at the College of Surgeons on two new Fossil Animals
Authors: E. Belfour
Journal: BMJ (1842)

when a cart-wheel passed over his right hand.On the evening of the same day I was requested to visit him, and found the structures of the thumb much contused and lacerated.I continued to visit him until the 8th of April, when he came to my house to have the in- jured part dressed; and, as he was going on favourably, I saw no more of him until the 17th, at 9, a.m.,
USEFULNESS OF FOLLOW-UP rCBF SPECT SCANNING IN THE DIFFERENTIAL DIAGNOSIS OF DEMENTIA
Authors: H. Golan, J. Kremer, M. Freedman, J. Kirsh, M. Ichise
Journal: Clinical Nuclear Medicine (1995)

Mount Sinai Hospital, Rotman Research Institute, Baycrest Center for Geriatric Care, and University of Toronto, Toronto Canada.
Medical Education in Indonesia
Authors: Mahar Mardjono, Marifin Husin, Peter J. Blizard
Journal: Annals of Internal Medicine (1981)

Abroad1 August 1981Medical Education in IndonesiaMAHAR MARDJONO, M.D., MARIFIN HUSIN, M.D., PETER J. BLIZARD, M.D.MAHAR MARDJONO, M.D.Search for more papers by this author, MARIFIN HUSIN, M.D.Search for more papers by this author, PETER J. BLIZARD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-2-234 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIndonesia has 13 government medical schools and 10 in the private sector. They produce more than 1200 new graduates each year, of whom more than 90% come from the government schools. In 1974 the Indonesian government reformulated its policies on newly graduated doctors, requiring them to spend 3 to 5 years in a rural, limited-technology government health center. In the succeeding 5 years more than 3500 of these centers were created, and most of them have a resident doctor. This policy change called for basic changes in the content of medical education and in pedagogic methods.The Consortium of Medical...References1. BLIZARDBLUNTALIBAZAHHUSIN PMPM. Introducing instructional objectives in Indonesian medical schools. Med Educ. 1978;12:273-81. CrossrefMedlineGoogle Scholar2. BLIZARDBLUNTALIBAZAHHUSIN PMPM. The long-term effectiveness of workshops in curriculum planning and design for teaching staff in Indonesian medical schools. Med Educ. 1980;14:154-63. CrossrefMedlineGoogle Scholar3. BLIZARDMACMAHONMAGIN PCD. Large-scale curriculum change in a system of ten Indonesian medical schools—A case study of educational innovation. Higher Education. 1980;9:573-603. CrossrefGoogle Scholar4. . The Reorientation of Medical Education to Community Needs. Report of an Intercountry Seminar, held in Surabaya, Indonesia, in June 1979. New Delhi, India: Regional Office for South-East Asia; 1980. Document SEA/Medical Education/369. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1981Volume 95, Issue 2Page: 234-235KeywordsGraduate medical educationMedical education Issue Published: 1 August 1981 PDF downloadLoading ...