tbuckley/cabot-search huggingface dataset:
New Rules: Regulation, Markets, and the Quality of American Health Care
Authors: R. J Maxwell
Journal: BMJ (1996)

Troyen A Brennan, Donald M Berwick Jossey-Bass, £28.25, pp 404 ISBN 0 7879 0149 0

Non-American readers will learn more from New Rules than they may want to know about the detailed history of regulation in the United States. But at times that history is fascinating, and the lessons that are drawn by Brennan and Berwick are undoubtedly relevant to us in Britain, as our accreditation systems begin to mimic those across the Atlantic, and the calls for regulation increase in the wake of any avoidable scandal.

It seems a pity that non-American experience gets no mention. Among the pioneers of audit, Florence Nightingale deserves recognition. More seriously, the omission of the British-based development …
Diffraction Methods of Measuring Red Cell Diameters
Authors: A. J. Hird
Journal: BMJ (1949)

CarriersDuring July three apparently healthy faecal carriers of Salm.paratyphi B phage type 3A were admitted and treated with chloramphenicol.The dosage given was 16.5 g. in seven days (0.5 g. four-hourly for four days, and then 0.25 g. four-hourly for three days).This dosage had no effect on the carrier state.Comment The satisfactory evaluation of the effect of chloram- phenicol is not possible in so small a series of cases, especially in the absence of a control group.The rapid improvement and clinical recovery which coincided with treatment, however, were most impressive.This was particularly so in those treated early in the disease.The dosage of chloramphenicol adequate to produce a well-marked clinical response did not in all cases render the faeces free from the infecting organisms.A similar observation was made in the case of typhoid fever by Woodward et al. (1949) and by Rumball and Moore (1949).In vitro tests showed that both Salm.paratyphi B phage type 3A, and Salm.paratyphi B phage type Taunton were sensitive to chloramphenicol.It was encouraging to note that in a case in which sensitivity tests were carried out after treatment the organism had not become resistant to chloramphenicol.It remains to be seen whether larger doses over longer periods will prevent the development of the convalescent carrier state, and whether the drug is effective in treatment of the chronic carrier condition.
The comparison between drainage, delayed excision and primary closure with excision and secondary healing in management of pilonidal abscess
Authors: Seyed V. Hosseini, Ali M. Bananzadeh, Maryam Rivaz, Babak Sabet, Mahnaz Mosallae, Saeedeh Pourahmad, Hooman Yarmohammadi
Journal: International Journal of Surgery (2006)
Abstract LB-43: MiR-147 is a novel tumor suppressor that reverses EMT and native resistance to EGFR inhibitors by inactivating Akt and activating Stat3.
Authors: Chang Gong Lee, Michael Gruidl, Cindy R. Timmee, Susan McCarthy, Timothy J. Yeatman
Journal: Cancer Research (2013)

Abstract Background: The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis, and resistance to chemotherapy. The EGFRi class of reagents are thought to target tumors with the epithelial phenotype. Hypothesis: We hypothesized that reversing this biological process through a mesenchymal to epithelial transition (MET), using a recently identified miR-147, might also lead to a reversal of resistance to EGFR inhibitors (EGFRi). Methods/Results: Following a screen of &amp;gt; 400 miRs, we recently identified miR-147 as highly correlated with an “intrinsic” and prognostic EMT gene expression signature derived from an unsupervised analysis of &amp;gt;2000 colorectal cancers. This suggested miR-147 might regulate the EMT program. We have shown that miR-147 is capable of reversing the EMT phenotype in vitro and converting EGFRi-resistant cells to sensitive cells. To further understand the mechanism underpinning this observation, we analyzed the genes affected by miR-147 over-expression in colon cancer cells using a global gene expression survey (Affymetrix). Among significantly altered genes, Akt expression was down-regulated (&amp;gt;2 fold) and Stat3 expression was up-regulated (&amp;gt;2 fold) by miR-147. Subsequent knock down of Akt with siRNA did induce MET and significantly increased EGFRi sensitivity. Western analysis showed increased Stat3 protein levels and total Stat3 phosphorylation with miR-147 transfection. Interestingly, knockdown of Stat3 inhibited the capacity of miR147 to reverse native EGFRi resistance. Conclusion: miR-147 induced MET and reversed resistance to EGFRi. This observation appears to be related to both the inhibition of Akt and to the induction of Stat3 activity. Understanding the precise mechanisms by which miRs regulate chemosensitivity and resistance will be important in designing more effective EGFRi therapies. Citation Format: Chang Gong Lee, Michael Gruidl, Cindy R. Timmee, Susan McCarthy, Timothy J. Yeatman. MiR-147 is a novel tumor suppressor that reverses EMT and native resistance to EGFR inhibitors by inactivating Akt and activating Stat3. [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 LB-43. doi:10.1158/1538-7445.AM2013-LB-43
Increased myogenic tone in skeletal muscle arterioles of diabetic rats. Possible role of increased activity of smooth muscle Ca2+ channels and protein kinase C
Authors: Z Ungvari
Journal: Cardiovascular Research (1999)

Objective: The diabetes mellitus-induced microangiopathy is still not clearly characterized. In this study we aimed to elucidate the effect of streptozotocin (STZ)-induced diabetes on myogenic response of isolated rat skeletal muscle arterioles and the mechanisms responsible for its alterations. Methods: Male rats were divided into two groups: (1) control rats (C, plasma glucose: 6.4±0.5 mmol/l, n=40) 2) diabetic rats (DM, 65 mg/kg STZ iv, plasma glucose: 25.7±0.7 mmol/l, n=40). Changes in diameter of isolated, cannulated gracilis skeletal muscle arterioles (∼130 μm in diameter) were measured by video-microscopy. Results: Step increases in perfusion pressure (PP; from 10 to 140 mmHg) elicited significantly greater constrictions in DM than in C gracilis arterioles, in the presence of the endothelium (E). Also, a step increase in PP (from 40 to 100 mmHg) elicited greater and faster constrictions in DM vs. C arterioles. There were no significant differences in the pressure-passive diameter (in Ca2+ free solution) curves of arterioles. Dilations to acetylcholine were impaired in arterioles of DM as compared to those of C rats (EC50, C: 4.0±0.9×10−9mol/l, DM: 4.8±2.0×10−8 mol/l (p<0.01), and unaffected by inhibition of nitric oxide synthesis with L-NNA (10−4 mol/l). Arteriolar constrictions to norepinephrine (NE) were significantly greater in DM compared to those of C rats (EC50, C: 6.2±0.6×10−7 mol/l, DM: 8.0±2.0 ×10−8 mol/l, p<0.01) both in the presence and absence of E. In the absence of the E, constrictions to increases in pressure, or Ca2+ (0.25–7.5 mmol/l), or the voltage-dependent Ca2+-channel agonist Bay K 8644 (EC50; DM: 4.2±1.5×10−10 mol/l, C: 1.7±0.8×10−9 mol/l, p<0.05) or the protein kinase C activator phorbol 12-myristate 13-acetate (PMA, EC50; DM: 6±2×10−9 mol/l, C: 2±1×10−8 mol/l, p<0.05) were significantly greater in arterioles of DM compared to those of C rats. Conclusion: The novel findings of our study are that in diabetes mellitus the myogenic response of rat skeletal muscle arterioles is enhanced, which seems to be independent from the impaired endothelial function present simultaneously, and likely due to the increased activity of voltage-dependent Ca2+ channels and/or upregulation of protein kinase C in arteriolar smooth muscle.
The effects of colcemid on hematopoiesis in the mouse.
Authors: P A Bunn, S E Shackney, S S Ford
Journal: Journal of Clinical Investigation (1976)

Colcemid was found to induce a dose and schedule dependent marrow magakaryocytosis and peripheral thrombocytosis. The response could be divided into early and late components. The early component appears to have been due to a direct stimulatory effect, probably by enhancement of endoreduplication in metaphase arrested megakaryocyte precursors. The ealy stimulatory response was blunted on toxic drug schedules. In contrast, the late component of the thrombopoietic response was demonstrated best on the most toxic drug schedules. It coincided temporally with the reactive restoration of the mononuclear marrow and blood cell elements, respectively. Thus, the late component appears to be a nonspecific rebound phenomenon. On comparing the thrombopoietic properties of Colcemid with those of the vinca alkaloids in experimental systems, the former appears to have a more favorable therapeutic index. The data suggest that colchicine and its derivatives may be useful agents in the treatment of clinical thrombocytopenic states.
Complementary medicine. Orthodox medicine isn't infallible.
Authors: D St George
Journal: BMJ (1993)

vascular granulomatosis or pulmonary "mainline" granulomatosis.'Symptoms include cough and dyspnoea, and in severe cases pulmonary hypertension is a consequence.Talc (magnesium trisilicate), a constituent of pentazocine, methyl- phenidate, and tripelennamine (tablets which are commonly injected) seems to be the agent most often implicated in such cases.Our evidence suggests that chronic misuse of injected temazepam may produce a similar pulmonary syndrome.We recently examined the lungs of a 31 year old drug misuser who died suddenly after an electromechanical dissociation cardiac arrest.He had admitted injecting a suspension of temazepam
HITlights: A career perspective on heparin‐induced thrombocytopenia
Authors: Theodore E. Warkentin
Journal: American Journal of Hematology (2012)

Abstract Two decades of research into heparin‐induced thrombocytopenia (HIT) permit a personal historical perspective on this fascinating syndrome. Previously, the frequency of HIT was unknown, although complicating thrombosis was believed to be rare and primarily arterial. The opportunity to apply a remarkable test for “HIT antibodies”—the 14 C‐serotonin‐release assay (SRA)—to serial plasma samples obtained during a clinical trial of heparin thromboprophylaxis, provided insights into the peculiar nature of HIT, such as, its prothrombotic nature—including its strong association with venous thrombosis (RR = 11.6 [95%CI, 6.4–20.8; P &lt; 0.0001); its more frequent occurrence with unfractionated versus low‐molecular‐weight heparin; the “iceberg” model, which states that among the many patients who form anti‐PF4/heparin antibodies during heparin therapy, only a minority whose antibodies evince strong platelet‐activating properties develop HIT; and the characteristic HIT timeline, whereby serum/plasma antibodies are readily detectable at or prior to the HIT‐associated platelet count fall. Applying the SRA also to patients encountered in clinical practice led to recognition of warfarin‐induced venous limb gangrene (for which HIT is a major risk factor via its extreme hypercoagulability) and delayed‐onset HIT (whereby thrombocytopenia begins or worsens following heparin discontinuation, due to the ability of HIT antibodies strongly to activate platelets even in the absence of heparin—so‐called heparin‐“independent” platelet activation). Recent concepts include the increasing recognition of HIT “overdiagnosis” (due to the low diagnostic specificity of the widely‐applied PF4‐dependent immunoassays), and the observation that HIT‐associated consumptive coagulopathy is a risk factor for treatment failure with PTT‐adjusted direct thrombin inhibitor therapy (“PTT confounding” secondary to HIT‐associated coagulopathy). Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Risk of suicide and spouse's psychiatric illness or suicide: nested case-control study
Authors: Esben Agerbo
Journal: BMJ (2003)

Suicides cluster in families with histories of psychiatric disorders and suicides.1 2 Genetic and environmental factors may play a role in the familial aggregation of suicides but are inseparable in most studies. Because married couples are usually genetically unrelated, studying them can identify environmental factors and means of protection. Your spouse dying or your spouse having a psychiatric disorder is stressful; mortality is increased in the surviving spouse.3 I investigated the association between a spouse's psychiatric illness, suicide, and other causes of death and own suicide.

I got data by linking population based registers using unique personal identification numbers, which are assigned to all people living in Denmark. Until 1993, suicide was defined as ICD-8 (international classification of diseases, 8th revision) codes …
A common coding variant in CASP8 is associated with breast cancer risk
Authors: Angela Cox, Alison M Dunning, Montserrat Garcia-Closas, Sabapathy Balasubramanian, Malcolm W R Reed, Karen A Pooley, Serena Scollen, Caroline Baynes, Bruce A J Ponder, Stephen Chanock, Jolanta Lissowska, Louise Brinton, Beata Peplonska, Melissa C Southey, John L Hopper, Margaret R E McCredie, Graham G Giles, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Lorna Gibson, Stig E Bojesen, Børge G Nordestgaard, Christen K Axelsson, Diana Torres, Ute Hamann, Christina Justenhoven, Hiltrud Brauch, Jenny Chang-Claude, Silke Kropp, Angela Risch, Shan Wang-Gohrke, Peter Schürmann, Natalia Bogdanova, Thilo Dörk, Rainer Fagerholm, Kirsimari Aaltonen, Carl Blomqvist, Heli Nevanlinna, Sheila Seal, Anthony Renwick, Michael R Stratton, Nazneen Rahman, Suleeporn Sangrajrang, David Hughes, Fabrice Odefrey, Paul Brennan, Amanda B Spurdle, Georgia Chenevix-Trench, Jonathan Beesley, Arto Mannermaa, Jaana Hartikainen, Vesa Kataja, Veli-Matti Kosma, Fergus J Couch, Janet E Olson, Ellen L Goode, Annegien Broeks, Marjanka K Schmidt, Frans B L Hogervorst, Laura J Van't Veer, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, Sara Wedrén, Per Hall, Yen-Ling Low, Jianjun Liu, Roger L Milne, Gloria Ribas, Anna Gonzalez-Neira, Javier Benitez, Alice J Sigurdson, Denise L Stredrick, Bruce H Alexander, Jeffery P Struewing, Paul D P Pharoah, Douglas F Easton
Journal: Nature Genetics (2007)
Longevity and C282Y mutation for haemochromatosis: Authors' reply
Authors: H. Coppin
Journal: BMJ (2003)

EDITOR–Although our primary goal was to test the hypothesis that people who are heterozygous for the HFE C282Y mutation would be underrepresented in a centenarian population, the coincidental discovery of two people who were homozygous among the centenarians raised several comments.

We agree with Li et al that the penetrance of a genotype depends …
Phagocytosis by macrophages and endothelial cells inhibits procoagulant and fibrinolytic activity of acute promyelocytic leukemia cells
Authors: Rui Xie, Chunyan Gao, Wen Li, Jiuxin Zhu, Valerie Novakovic, Jing Wang, Ruishuang Ma, Jin Zhou, Gary E. Gilbert, Jialan Shi
Journal: Blood (2011)
Home Characteristics as Predictors of Bacterial and Fungal Microbial Biomarkers in House Dust
Authors: Joanne E. Sordillo, Udeni K. Alwis, Elaine Hoffman, Diane R. Gold, Donald K. Milton
Journal: Environmental Health Perspectives (2010)

BackgroundMeasurement of fungal and bacterial biomarkers can be costly, but it is not clear whether home characteristics can be used as a proxy of these markers, particularly if the purpose is to differentiate specific classes of biologic exposures that have similar sources but may have different effects on allergic disease risk.ObjectiveWe evaluated home characteristics as predictors of multiple microbial biomarkers, with a focus on common and unique determinants and with attention to the extent of their explanatory ability.MethodsIn 376 Boston-area homes enrolled in a cohort study of home exposures and childhood asthma, we assessed the relationship between home characteristics gathered by questionnaire and measured gram-negative bacteria (GNB) (endotoxin and C10:0, C12:0, and C14:0 3-hydroxy fatty acids), gram-positive bacteria (GPB) (N-acetyl muramic acid), and fungal biomarkers [ergosterol and (1→6) branched, (1→3) β-d glucans] in bed and family room dust.ResultsHome characteristics related to dampness were significant predictors of all microbial exposures; water damage or visible mold/mildew in the home was associated with a 20–66% increase in GNB levels. Report of cleaning the bedroom at least once a week was associated with reduced GNB, GPB, and fungi. Presence of dogs or cats predicted increases in home bacteria or fungi. The proportion of variance in microbial biomarkers explained by home characteristics ranged from 4.2% to 19.0%.ConclusionsDespite their associations with multiple microbial flora, home characteristics only partially explain the variability in microbial biomarker levels and cannot substitute for specific microbial measurements in studies concerned with distinguishing effects of specific classes of microbes.
Commercial National Board Review Programs
Authors: Lloyd A. Lewis
Journal: JAMA (1978)

For a long period, students have been taking national board examination review programs offered by commercial firms. The one question to which faculty and students would like the answer is, "Do the national board review programs offered by these commercial firms do any good?" Events at the Medical College of Georgia have provided an opportunity to gather data toward an answer to this question. In 1976, thirty-three medical students at the Medical College of Georgia enrolled in a commercial national board review program. Performance of these students was compared with the predicted performance of these students had they not taken the national board review program. The results suggest that the commercial review program did not notably help these students.
Molecular cloning of human synovial cell collagenase and selection of a single gene from genomic DNA.
Authors: C E Brinckerhoff, P L Ruby, S D Austin, M E Fini, H D White
Journal: Journal of Clinical Investigation (1987)

We used a subclone of a rabbit genomic clone for collagenase that cross-hybridizes with human synovial cell messenger RNA (mRNA) to identify a human collagenase complementary DNA (cDNA) clone. The human cDNA clone is 2.1 kilobases (kb) and selects a mRNA transcript of approximately the same size from primary cultures of rheumatoid synovial cells that produce collagenase, but no mRNA is selected from control (nonproducing) synovial fibroblasts. Restriction enzyme analysis and DNA sequence data indicate that our cDNA clone is full length and that it is identical to that recently described for human skin fibroblast collagenase. The cDNA clone identified a single collagenase gene of approximately 17 kb from blots of human genomic DNA. The identity of human skin and synovial cell collagenase and the ubiquity of this enzyme and of its substrates, the interstitial collagens types I, II, and III, imply that common mechanisms controlling collagenolysis throughout the human body may be operative in both normal and disease states.
Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells. An endothelin B receptor-mediated pathway.
Authors: A Mallat, L Fouassier, A M Préaux, C S Gal, D Raufaste, J Rosenbaum, D Dhumeaux, C Jouneaux, P Mavier, S Lotersztajn
Journal: Journal of Clinical Investigation (1995)

Ito cells play a pivotal role in the development of liver fibrosis associated with chronic liver diseases. During this process, Ito cells acquire myofibroblastic features, proliferate, and synthesize fibrosis components. Considering the reported mitogenic properties of endothelin-1 (ET-1), we investigated its effects on the proliferation of human Ito cells in their myofibroblastic phenotype. Both ET receptor A (ETA: 20%) and ET receptor B (ETB: 80%) binding sites were identified, using a selective ETA antagonist, BQ 123, and a selective ETB agonist, sarafotoxin S6C (SRTX-C). ET-1 did not stimulate proliferation of myofibroblastic Ito cells. In contrast, ET-1 inhibited by 60% DNA synthesis and proliferation of cells stimulated with either human serum or platelet-derived growth factor -BB (PDGF-BB). PD 142893, a nonselective ETA/ETB antagonist totally blunted this effect. SRTX-C was as potent as ET-1, while BQ 123 did not affect ET-1-induced growth inhibition. Analysis of the intermediate steps leading to growth-inhibition by ET-1 revealed that activation of mitogen-activated protein kinase by serum or PDGF-BB was decreased by 50% in the presence of SRTX-C. In serum-stimulated cells, SRTX-C reduced c-jun mRNA expression by 50% whereas c-fos or krox 24 mRNA expression were not affected. We conclude that ET-1 binding to ETB receptors causes a potent growth inhibition of human myofibroblastic Ito cells, which suggests that this peptide could play a key role in the negative control of liver fibrogenesis. Our results also point out that, in addition to its well known promitogenic effects, ET-1 may also exert negative control of growth on specific cells.
Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.
Authors: W Scheithauer, H Rosen, G V Kornek, C Sebesta, D Depisch
Journal: BMJ (1993)

OBJECTIVES--To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care. DESIGN--Randomised study. SETTING--Gastrointestinal oncology departments. PATIENTS--40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic. INTERVENTIONS--Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle. MAIN OUTCOME MEASURES--Length of survival and quality of life score with an optimised functional living index-cancer scale. RESULTS--Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm. CONCLUSIONS--In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.
Rac, a small guanosine triphosphate–binding protein, and p21-activated kinase are activated during platelet spreading on collagen-coated surfaces: roles of integrin α2β1
Authors: Katsue Suzuki-Inoue, Yutaka Yatomi, Naoki Asazuma, Mie Kainoh, Toshiaki Tanaka, Kaneo Satoh, Yukio Ozaki
Journal: Blood (2001)