tbuckley/cabot-search huggingface dataset:
Use of psychiatric drug treatment services by heroin users from general practice.
Authors: A B Bucknall, J R Robertson, J G Strachan
Journal: BMJ (1986)

Centres for the treatment of drug abusers are often integrated with regional psychiatric hospitals and are the focus of the British response to opiate addiction. Little is known, however, about the use made of these services by drug users in the community or about the success of these services. This study examined the use made of one centre offering a detoxification service by a cohort of 183 heroin users from a large Scottish general practice. Over half of this cohort were referred to the psychiatric drug treatment service, but less than one third started treatment. The evidence did not indicate that patients who had extended contact with the psychiatric service showed prolonged abstinence, though methodological difficulties necessitate further prospective studies. This study raises important questions about the value and appropriateness of this type of service in the light of the pattern of voluntary remission and relapse displayed by heroin users and in the absence of adequate provision for drug abusers in the community.
Model of outcomes of screening mammography: Authors' reply
Authors: Alexandra Barratt, Kirsten Howard, Les Irwig, Glenn Salkeld, Nehmat Houssami
Journal: BMJ (2005)

EDITOR—Zahl and Maehlen and G⊘tzsche and J⊘rgensen cite a variety of evidence, consistent with our model, to propose that overdetection (and potentially overtreatment) may be substantial in breast screening. Furthermore, Zahl and Maehlen say that the biological mechanisms underlying the observed overdetection may include regression of small cancers, as well as non-progression.

Although the frequency of regression is as yet very unclear, evidence from epidemiology and cancer biology …
Abstract 5273: Systematic functional screening, miRNA and target expression analyses reveal miR-19, -124, -583, -129 and -876 as key nodes in prostate cancer proliferation networks.
Authors: Päivi Östling, Suvi-Katri Leivonen, Pekka Kohonen, Anna Aakula, Petteri Hintsanen, Tero Aittokallio, Merja Perälä, Olli Kallioniemi
Journal: Cancer Research (2013)

Abstract To discover microRNA (miRNA) regulation of pathways relevant for proliferation of prostate cancer cells we performed gain-of-function screening with 1129 miRNA molecules in five prostate cancer (PCa) cell lines. Using proliferation, viability and apoptosis as read out we identified 25 miRNAs increasing and 48 miRNAs decreasing cell viability (threshold FDR q-value 3000 genes containing the predicted targets (TargetScan) and performed gene set enrichment analysis (MSigDB v. 2.07). Positively enriched gene sets (total of 17, q-value &amp;lt;0.01) contained signatures such as mitosis and androgen signalling and the most enriched gene was AURKA. The negatively enriched gene sets (total of 207, q-value &amp;lt;0.01) involved Ras-signaling and focal adhesion and the most down regulated gene was CAV1. Network visualization of the core target genes identified five miRNAs (hsa-miR-19a, −32, -124a, -583 and −876–3p) predicted to regulate both the positively and negatively enriched target genes suggesting a central role for both these miRNAs and the core targets in PCa. Our systematic screening approach combined with in vivo expression, gene set enrichment analyses and network visualization provide an unbiased way of revealing novel miRNAs -core targets important in PCa. Citation Format: Päivi Östling, Suvi-Katri Leivonen, Pekka Kohonen, Anna Aakula, Petteri Hintsanen, Tero Aittokallio, Merja Perälä, Olli Kallioniemi. Systematic functional screening, miRNA and target expression analyses reveal miR-19, -124, -583, -129 and -876 as key nodes in prostate cancer proliferation networks. [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 5273. doi:10.1158/1538-7445.AM2013-5273
Standard of Care — In Sickness and in Health and in Emergencies
Authors: George J. Annas
Journal: New England Journal of Medicine (2010)

After 9/11, policy analysts speculated that clinicians may be reluctant to provide care during disasters because of fear of medical liability and proposed policies to create different standards of care for emergencies. In the context of the Haitian earthquake, the author argues that redefining the standard of care in disasters is neither necessary nor justified.
Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation
Authors: Sophia Bornstein, Ruth White, Stephen Malkoski, Masako Oka, Gangwen Han, Timothy Cleaver, Douglas Reh, Peter Andersen, Neil Gross, Susan Olson, Chuxia Deng, Shi-Long Lu, Xiao-Jing Wang
Journal: Journal of Clinical Investigation (2009)

Smad4 is a central mediator of TGF-β signaling, and its expression is downregulated or lost at the malignant stage in several cancer types. In this study, we found that Smad4 was frequently downregulated not only in human head and neck squamous cell carcinoma (HNSCC) malignant lesions, but also in grossly normal adjacent buccal mucosa. To gain insight into the importance of this observation, we generated mice in which Smad4 was deleted in head and neck epithelia (referred to herein as HN-Smad4–/– mice) and found that they developed spontaneous HNSCC. Interestingly, both normal head and neck tissue and HNSCC from HN-Smad4–/– mice exhibited increased genomic instability, which correlated with downregulated expression and function of genes encoding proteins in the Fanconi anemia/Brca (Fanc/Brca) DNA repair pathway linked to HNSCC susceptibility in humans. Consistent with this, further analysis revealed a correlation between downregulation of Smad4 protein and downregulation of the Brca1 and Rad51 proteins in human HNSCC. In addition to the above changes in tumor epithelia, both normal head and neck tissue and HNSCC from HN-Smad4–/– mice exhibited severe inflammation, which was associated with increased expression of TGF-β1 and activated Smad3. We present what we believe to be the first single gene–knockout model for HNSCC, in which both HNSCC formation and invasion occurred as a result of Smad4 deletion. Our results reveal an intriguing connection between Smad4 and the Fanc/Brca pathway and highlight the impact of epithelial Smad4 loss on inflammation.
Illustrated Manual of Regional Anesthesia
Authors: Honorio T. Benzon
Journal: JAMA (1989)

This book is a radical departure from other illustrated regional anesthesia textbooks. It actually consists of two "books." One is a massive atlas that has 300 loose-leaf transparent illustrations of regional anatomy and regional nerveblock techniques. The other is an accompanying 96-page text brochure that describes each technique (the Basic Set). The superb but fragile three-dimensional transparencies are the result of a new state-of-the-art printing process that employs laser beams to color the illustrations, giving a realistic presentation of the deeper anatomic structures. The transparencies are surrogate cadavers that make up for the decreased time spent by medical students in anatomy classrooms. Several transparencies make up an illustration. Usually, the first one is the surface anatomy, followed by the overlying muscles, the vertebrae, the vascular supply, and then the nerves. I found that not all are needed. For example, transparency 5 is better when transparencies 5.2 and 5.4 are removed.
Functional Pathology of the Human Adrenal Gland
Authors: William B. Ober
Journal: JAMA (1970)

Science advances swiftly these decades, and a monograph on the pathology of a single organ runs the risk of rapid obsolescence from new discoveries in biochemistry and physiology or new technical advances. Professor Symington, to complete his synoptic view of the<i>functional</i>pathology of the human adrenal gland, chose the propitious time of 1969, when the advances of the 1950s and 1960s regarding the biochemistry and physiologic action of adrenocortical steroids and medullary amines have been consolidated. In the best tradition of Scottish anatomy, both gross and microscopical, Symington has put together a text based on historical knowledge, brought up to date by his gift for synthesizing information and his particular knack for relating symptoms to lesions. Rarely can a pathologist be equally so at home in the clinic, the biochemistry laboratory, and the laboratory of morbid anatomy. The value of this monograph lies in its broad range, its firm
Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects
Authors: R. A. Brown, G. W. Clarke, C. L. Ledbetter, M. J. Hurle, J. C. Denyer, D. E. Simcock, J. E. Coote, T. J. Savage, R. D. Murdoch, C. P. Page, D. Spina, B. J. O’Connor
Journal: European Respiratory Journal (2007)

Asthmatics, unlike healthy subjects, experience bronchoconstriction in response to inhaled adenosine, and extracellular adenosine concentrations are elevated in the bronchoalveolar lavage fluid and exhaled breath condensate of asthmatic subjects. However, little is known about the location and expression of adenosine receptors in asthmatic airways. The aim of the present study was to investigate the distribution of adenosine A(1) receptors in bronchial biopsy specimens from mildly asthmatic steroid-naïve subjects and then compare the degree of expression with that of healthy subjects. Biopsy sections were immunostained using an adenosine A(1) receptor antibody, the selectivity of which was validated in specific experiments. Image analysis was then performed in order to determine differences in immunostaining intensity. Immunostaining of biopsy sections from the asthmatic subjects revealed strong expression of the A(1) receptor, located predominantly in the bronchial epithelium and bronchial smooth muscle. In comparison, very weak immunostaining was observed in biopsy specimens obtained from healthy subjects. Image analysis revealed that the intensity of positive staining of the asthmatic bronchial epithelium and smooth muscle regions was significantly greater than that observed for the healthy epithelium and smooth muscle. In conclusion, the sensitivity of asthmatics to inhaled adenosine coupled with increased adenosine A(1) receptor expression implies that these receptors play a role in the pathophysiology of this disease.
PIF-like Transposons are Common in Drosophila and Have Been Repeatedly Domesticated to Generate New Host Genes
Authors: C. Casola, A. M. Lawing, E. Betran, C. Feschotte
Journal: Molecular Biology and Evolution (2007)

The P instability factor or PIF superfamily of DNA transposons constitutes an important group of transposable elements (TEs) in plants, but it is still poorly characterized in metazoans. Taking advantage of the availability of draft genome sequences for twelve Drosophila species, we discovered 4 different lineages of Drosophila PIF-like transposons, named DPLT1-4. These lineages have experienced a complex evolutionary history during the Drosophila radiation, involving differential amplification and retention among species and probable events of horizontal transmission. Like previously described plant and animal PIF transposons, full-length DPLTs encode a putative transposase as well as a second predicted protein containing a Myb/SANT domain. In DPLTs, this domain is most closely related to the MADF DNA-binding domain found in several Drosophila transcription factors. In addition, we identified 7 distinct genes distributed across the Drosophila genus that encode proteins related to PIF transposases, but lack the hallmarks of transposons. Instead, these sequences show features of functional genes, such as an intact coding region evolving under purifying selection, the presence of orthologs in at least 2 Drosophila species, and the conservation of intron/exon structure across orthologs. We also provide evidence that most of these genes are transcribed and that some are developmentally regulated. Together the data indicate that these genes derived from PIF-transposons that have been "domesticated" to serve cellular functions. In one instance the recruitment of the transposase gene was accompanied by the co-recruitment of the adjacent second PIF gene, which raises the hypothesis that both proteins now function in the same pathway. The second PIF gene has retained the capacity to encode a protein with an intact MADF domain, suggesting that it may function as a transcription factor. We conclude that PIF transposons are common in the Drosophila lineage and have been a recurrent source of new genes during Drosophila evolution.
Clonidine, a New Antihypertensive Drug
Authors: William A. Pettinger
Journal: New England Journal of Medicine (1975)

CLONIDINE (Catapres, ST-155) recently became available for use by prescription in the United States as an antihypertensive drug. It is highly effective in patients with either moderate or severe hypertension, but the magnitude of response cannot be predicted a priori in the individual subject. In contrast to most other antihypertensive agents, the dose is remarkably low, in the range of 0.2 to 2.4 mg per day. Blood pressure is lowered in both supine and standing positions, with little tendency to additional decreases in the standing position. Orthostatic symptoms are considerably less than with ganglionic blockers, monoamine oxidase inhibitors and sympathetic . . .
Clinical Experience with the Melrose Oxygenator at Normal and Reduced Temperatures
Authors: P. G. F. Nixon, V. A. Grimshaw, L. A. Catchpole, H. M. Snow, K. Lawrance
Journal: Thorax (1960)

A heart-lung machine was used in the surgical treatment of 20 patients with congenital heart disease and one patient with rheumatic mitral incompetence during the latter half of 1959 in the Department of Thoracic Surgery in the General Infirmary at Leeds.One patient died a month after perfusion from staphylococcal septicaemia, and one died from heart block on the third day after operation.Nineteen are alive and well.The essential parts of the heart-lung machine are an oxygenator, a pump (Nixon, 1959a), a filter and bubble trap, and a heat-exchanger.Catheters in the superior and inferior caval veins permit blood flowing from the upper and lower parts of the body to be directed away from the heart and syphoned into the oxygenator.The pump returns the flow to the femoral artery.Before blood reaches the femoral artery it is passed through a heat-exchanger consisting of a series of thin-walled metal tubes set in a water jacket of variable temperature, and through a wire-mesh filter and bubble-trap.The latter is provided with a mercury manometer and warning device to act as a flow-meter and guard against obstruction to flow (Nixon, 1959b).The oxygenator was designed by Melrose (1953).It is a rotating cylinder set at a slight angle to the horizontal and composed of a number of perspex plates bolted together.As blood travels through the central lumen under the influence of gravity it is filmed over blades which project from the wall, somewhat after the form of an Archimedean helix.A report of its successful use in the U.S.A. has been made by Gerbode, Melrose, Norman, Osborn, Perkins, and Baer (1958), and in England by Cleland, Beard, Bentall, Bishop, Braimbridge, Bromley, Goodwin, Hollman, Kerr, Lloyd-Jones, Melrose, and Telivuo (1958).These authors did not deliber- ately cool their patients.In Leeds the work of preparation and assembly has been eased by the use of modified plates (Catchpole and Nixon, 1959).370 C. a flow of 2.4 litres per square metre of body surface per minute was used.
Consensus Reports From the Convinced: Manipulating the Information Transfer Process for Drug Promotion
Authors: Robert S. Stern
Journal: JAMA (1991)

To the Editor. —  The use of many potent but toxic drugs outside their established indications has both advocates and skeptics within the medical profession. In an effort to provide up-to-date data about appropriate drug use, organizations such as the American Medical Association and the US Pharmacopeia publish drug evaluations that reflect the medical literature and the opinions of expert consultants. 1,2 The consensus conference is another means of addressing controversies about the use of medical therapies. Typically, at consensus conferences, proponents of alternative therapeutic approaches present data to a panel of nonpartisan experts. 3 The panel then promulgates what it believes are reasonable practices based on current knowledge and suggests what additional data are needed to adequately assess the appropriate role of controversial treatments. 3,4   Recently, Sandoz Pharmaceuticals, Hanover, NJ, distributed a three-page report entitled Consensus Report: Cyclosporine-A for Psoriasis to selected American dermatologists. 5 According to the accompanying
Screening Data from the Cancer Chemotherapy National Service Center Screening Laboratories. XVIII
Authors: Joseph Leiter, B. J. Abbott, Saul A. Schepartz, I. Wodinsky
Journal: Cancer Research (1964)

Data are reported on 1955 randomly selected synthetic compounds which failed the CCNSC primary screens. Most of the materials were tested against Sarcoma 180, Adenocarcinoma 755 and Leukemia L1210. Cell-culture cytotoxicity results for these materials are included.
A man with generalised lymphadenopathy
Authors: Rosalie Magro, Andrew Borg
Journal: BMJ (2014)

A 75 year old man with Paget’s disease, hypercholesterolaemia, and hypertension presented with a three year history of multiple neck lumps, which had never been investigated and had increased in size over the past two months. He felt generally well and had no history of fever or weight loss. His appetite was normal and there was no change in bowel habit. Clinical examination showed no abnormalities and he had no shortness of breath, chest pain, lower limb oedema, joint pains, or neurological symptoms.

On examination, he had hepatomegaly (width of three fingers) and his cervical, axillary, and inguinal lymph nodes were enlarged, hard, and non-tender bilaterally. His blood count, renal function, and C reactive protein (<57 nmol/L; reference range 0-95) were normal. He had a raised erythrocyte sedimentation rate (102 mm in the first hour (28-32) and altered liver function tests (alkaline phosphatase 6.5 µkat/L (0.67-2.15), alanine aminotransferase 0.35 µkat/L (0.08-0.68), γ-glutamyl transferase 9.67 µkat/L (0.13-1.02), and total bilirubin 29.5 µmol/L (1.72-17.1). Proteinuria (0.25 g/L) was noted on urinalysis. Chest radiography showed mediastinal lymphadenopathy. Computed tomography of the thorax, abdomen, and pelvis showed enlarged mediastinal, axillary, and inguinal lymph nodes, which varied in size from 1 cm to 3 cm, with eggshell calcifications and an enlarged liver with hypodense texture.

A lymph node biopsy was done and histological analysis performed (figure⇓). 



Fig 1 Section from a lymph node biopsy stained with Congo red and viewed under polarised light. Image courtesy of Ed Uthman, Houston, Texas, with permission1 





### 1. What are the causes of generalised lymphadenopathy?

#### Short answer

Generalised lymphadenopathy can be caused by infections (viruses, bacteria, fungi, or protozoans), cancer (including lymphoproliferative disorders), autoimmune disorders (including …
Household insects allergy
Authors: RC Panzani, R. Ariano
Journal: Allergy (2003)

I read with great interest the paper by Dr Carlsen et al. ‘Cockroach sensitivity in Norway: a previously unidentified problem?’ (1) and also Dr Chapman's editorial (2) in the same issue of your journal. In order to answer the question in Dr Carlsen's paper, in my opinion it would be interesting to know: (1) What are the commonest household insects found in Norway? (2) What is the mosquito species used for radioallergosorbent test (RAST) and why has the same extract not been used for the skin test? The fact that 16.5% of the patients are sensitive to mosquito seems to indicate a cross-reactivity with house fly (Musca domestica) which is also a diptera. As it is known that a pan-allergy among arthropods is very common (3–6) and related to tropomyosin (7), paramyosin, carbohydrate cross-reactive determinants (CCD) or other pan-allergens, I think that there is more likely to be a cross-reactivity with other household insect allergens such as spider, cloth mite, Ephestia and silverfish or others specific to Norway in the case of Dr Carlsen's study. In Roma, with Barletta et al. (8), we have shown that silverfish (Lepisma saccharina) is very common and a very primitive insect and a potential allergen. I should be very glad to have the results of their investigations in order to know whether my guess is correct.
Effect of FCGR2A and FCGR3A variants on CLL outcome
Authors: David Dornan, Olivia Spleiss, Ru-Fang Yeh, Guillemette Duchateau-Nguyen, Annika Dufour, Jianguo Zhi, Tadeusz Robak, Sergey I. Moiseev, Anna Dmoszynska, Philippe Solal-Celigny, Krzysztof Warzocha, Javier Loscertales, John Catalano, Boris V. Afanasiev, Loree Larratt, Viktor A. Rossiev, Isabelle Bence-Bruckler, Christian H. Geisler, Marco Montillo, Michael K. Wenger, Martin Weisser
Journal: Blood (2010)

Abstract Polymorphisms of activating Fc-γ receptors (FCGRs) on natural killer cells and macrophages result in variable affinity for immunoglobulin G1 monoclonal antibodies and subsequently modulate antibody-dependent cellular cytotoxicity (ADCC) activity. Whether single-nucleotide polymorphisms of FCGRs correlate with survival of chronic lymphocytic leukemia (CLL) patients treated with a monoclonal antibody containing regimen is unclear. We assessed the FCGR3A and FCGR2A genotype of patients enrolled in the REACH trial, where patients received fludarabine and cyclophosphamide (FC) or rituximab plus FC (R-FC). FCGR3A and FCGR2A polymorphisms did not demonstrate prognostic significance in the FC arm (P = .42 and P = .64, respectively) or R-FC arm (P = .41 and P = .88, respectively) with respect to progression free survival. Patients with intermediate affinity genotypes (FV and HR) benefited significantly from addition of rituximab (hazard ratio = 0.55 [0.37-0.8 CI]; P = .0017 and hazard ratio = 0.63 [0.44-0.9 CI]; P = .011, respectively). Similar benefit was suggested for patients with high- affinity VV and HH (hazard ratio = 0.86 [0.4-1.84 CI]; P = .7 and hazard ratio = 0.7 [0.41-1.18 CI]; P = .18, respectively) and low-affinity FF and RR (hazard ratio = 0.85 [0.56-1.29 CI]; P = .44 and hazard ratio = 0.82 [0.47-1.42 CI]; P = .48, respectively). Overall, our results suggest that FCGR2A and FCGR3A polymorphisms do not significantly influence the outcomes of relapsed or refractory CLL patients treated with FC or the monoclonal antibody regimen R-FC.
Prolonged Maintenance of Active Cytochrome P-450 in Adult Rat Hepatocytes Co-Cultured with Another Liver Cell Type
Authors: Jean-Marc Begue, Christiane Guguen-Guillouzo, Nicole Pasdeloup, Andre Guillouzo
Journal: Hepatology (1984)

The cytochrome P-450 content promptly fell in adult rat hepatocytes cultured in conventional conditions whereas no obvious change was detected over a 10-day period when these cells were co-cultured with another rat liver epithelial cell type. A concomitant maintenance of the amino-pyrine N -demethylase activity and a high aflatoxin B 1 -induced cytotoxicity was observed, and addition of phenobarbital to the culture medium produced about a 2-fold increase in cytochrome P-450 level. These results indicate that when placed in co-culture, adult hepatocytes remain differentiated for several days and suggest that such a co-culture system is an appropriate model for pharmacotoxicological studies.
Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma
Authors: Randy D. Gascoyne, Sheryle A. Adomat, Stanislaw Krajewski, Maryla Krajewska, Douglas E. Horsman, Anthony W. Tolcher, Susan E. O'Reilly, Paul Hoskins, Andrew J. Coldman, John C. Reed, Joseph M. Connors
Journal: Blood (1997)