tbuckley/cabot-search huggingface dataset:
Lower-Extremity Amputations in Diabetic and Nondiabetic Patients: A population-based study in eastern Finland
Authors: Onni I Siitonen, Leo K Niskanen, Markku Laakso, Jukka T Siitonen, Kalevi Pyörälä
Journal: Diabetes Care (1993)

Objective— To study the incidence of LEAs attributable to PVD in diabetic and nondiabetic patients. The age at first amputation, the level of amputation, the number of reamputations, and survival after amputation also were examined in the study populations. Research Design and Methods— This retrospective study was based on a population of 253,000 inhabitants in eastern Finland. All patients with their first LEA performed during the period from 1 January 1978 to 31 December 1984 were identified from the registers of operation theaters in the study area. Furthermore, patient records and death certificates were reviewed. Amputations attributable to causes other than evident atherosclerotic vascular disease were excluded. Results— Altogether, 477 patients (85 diabetic men, 127 nondiabetic men, 169 diabetic women, and 96 nondiabetic women) were identified. The overall LEA rate was 26.9/100,000 per yr, and the incidence increased strongly with age in both diabetic and nondiabetic patients. The age-adjusted amputation incidence per yr was 349.1/100,000 for diabetic men, 33.9/100,000 for nondiabetic men, 239.4/100,000 for diabetic women, and 17.2/100,000 for nondiabetic women. The proportion of peripheral (toe, leg) amputations was markedly higher in diabetic patients who also tended to have more reamputations during the follow-up than did nondiabetic subjects. The diabetic status per se was a statistically significant risk factor for mortality in women, but not in men. Conclusions— Diabetic men and women had a 10.3- and 13.8-fold higher risk, respectively, for LEA.
Consultation–Liaison Psychiatry Activities in a Renal Transplant Unit
Authors: Hellmuth Freyberger, Marianne Ludwig, Marlene Mangels, Peter Neuhaus
Journal: Psychotherapy and Psychosomatics (1979)

We describe the consultation–liaison psychiatry activities in the renal transplant unit at Hannover Medical School. The activities with regard to patients' care include: the group session, with particular regard to dealing with the patients' denial; the indirect and direct psychotherapeutic interventions, the latter concerning psychotherapeutic consultation and counselling ('supportive psychotherapy'); and dealing with live donors and potential renal transplant patients. The second consultation–liaison psychiatry activity includes the teaching procedures: firstly, Balint-group-work with the nurses, secondly, the nurses' presence in the group sessions, and finally, Balint-group-work with students working as auxiliary therapists. In the authors' view, the field of surgery can represent a very promising one with regard to consultation-liaison psychiatry.
806-4 Association of Ventricular Arrhythmias with Left Ventricular Remodeling After Myocardial Infarction: Is it a Missing Link?
Authors: Aleksandar D. Popović, Kočo Pavlovski, Aleksandar N. Nešković, Jelena Marinković, Rade Babić, James D. Thomas
Journal: Journal of the American College of Cardiology (1995)
Young Man With Pain in the Chest and Pulmonary Infiltrate in the Left Lower Lobe
Authors: Glenn F. Ragalie
Journal: JAMA (1984)

<h3>History</h3> A 32-year-old, previously healthy man had a five-day history of worsening dull, constant, left-sided anterolateral pain in the chest accompanied by several nonbloody diarrheal stools. No dyspnea, recent or remote trauma, fever, cough, or prior similar symptoms were present. He had lifted heavy weights (36 kg to 50 kg [80 lb to 110 lb]) on every other day during the preceding two months as conditioning exercises. Lifting exercises such as curls, bench press, and "squats" with Valsalva's maneuver were performed by him as late as the evening before the symptoms began. A roentgenogram of the chest obtained four years earlier was unavailable but was reportedly normal. Physical examination findings were normal except for dullness to percussion and diminished breath sounds over the base of the left lung. Complete blood cell count, screening chemistry findings, amylase level, and urinalysis results were normal. Roentgenograms of the chest are shown in Figs
Old authoritarian patterns of doctors' behaviour are still alive and well in California, study shows
Authors: B. Roehr
Journal: BMJ (2012)

Patients have a strong desire to engage in shared decision making about treatment with their doctor, but the way the doctor behaves can inhibit this interaction, a new study concludes.

The issue is important for reasons of patient satisfaction, compliance in following the prescribed regimen, and in achieving less aggressive and less expensive care, it says.

The study, conducted by the Palo Alto Medical Foundation Research Institute, randomly recruited 48 people aged 40 years or older from among primary care practices serving well educated, upper income people in the San Francisco Bay area to …
Abstract 5027: MicroRNA profiling of diagnostic fine needle aspirates of pancreatic cancer preserved as formalin-fixed paraffin-embedded cell blocks
Authors: Shadan S. Ali, Husain Saleh, Seema Sethi, Fazlul H. Sarkar, Philip A. Philip
Journal: Cancer Research (2012)

Abstract MicroRNA (miRNA) expression profiling and quantitative real-time PCR (qRT-PCR) from fine needle aspirates (FNA) of formalin-fixed paraffin-embedded cell blocks (FFPE) could be a major improvement for prognosis and predicting treatment response in inoperable tumors of pancreatic cancer (PC). MicroRNA (miRNA) profiling provides a more comprehensive molecular interrogation of tumors. In the present study, miRNA expression profiling was performed on formalin-fixed paraffin-embedded cell blocks (FFPE) from FNA of suspicious pancreatic masses. Subjects were retrospectively studied and included those who had a pathological diagnosis of pancreatic adenocarcinoma and others with no histological proof of any cancer. We compared the expression profile of miRNAs in the pooled samples of FNA blocks from patients diagnosed with PC (n=29) with normal controls (n=15). MicroRNA profiling confirmed the deregulation of over 228 miRNAs of which, the top seven were validated by qRT-PCR. The expression of let-7c, let-7f, and miR-200c were significantly lower in almost all of the 29 patients compared to normal samples. On the contrary, the expression level of miR-486-5p, and miR-451 were significantly higher in all PC samples. Interestingly, two of the miRNAs, let-7d and miR-423-5p, that showed significant down-regulation or up-regulation in pooled sample showed a differential expression between the samples with individual qRT-PCR. These results suggest that identifying seven-miRNA signatures for PC in FNA cell blocks and validating with qRT-PCR can provide a strategy for improving the diagnosis of PC by using minimally invasive procedures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5027. doi:1538-7445.AM2012-5027
Transcriptional analysis of the molecular basis of human kidney aging using cDNA microarray profiling
Authors: Anette Melk, Elaine S. Mansfield, Szu-Chuan Hsieh, Tina Hernandez-Boussard, Paul Grimm, David C. Rayner, Philip F. Halloran, Minnie M. Sarwal
Journal: Kidney International (2005)
Abstract 5650: Determinants of acquired resistance to PI3K/mTOR inhibition in cells refractory to EGFR inhibition.
Authors: King Xin Koh, Bhaskar Bhattacharya, Joanne Loh, Hong Kiat Ng, Ross Soo, Barry Iacopetta, Richie Soong
Journal: Cancer Research (2013)

Abstract Acquired resistance to EGFR inhibitors can be mediated through PI3K/mTOR pathway activation. This has prompted the consideration of PI3K/mTOR inhibitors for treatment of EGFR inhibitor-refractory non-small cell lung cancer (NSCLC). This study aimed to generate and elucidate mechanisms of acquired resistance to BEZ235, a PI3K/mTOR inhibitor, in H1975 NSCLC cells containing the EGFR T790M resistance mutant. IC50 values of compounds were determined at 72 hours using the MTS assay. Acquired resistant clones of H1975 were generated by continual exposure of H1975 cells to parental IC50 concentrations of BEZ235, followed by monoclonal selection. Protein levels, cell invasion/migration, and cell cycle analysis were evaluated using standard techniques. Apoptosis was measured using Roche Cell Death kit. Two resistant clones were generated with stably higher IC50 values (Clone 5 2.29uM, Clone 6 1.94uM) to parental H1975 cells (0.32uM) after 6 months. The clones were resistant to other PI3K/mTOR inhibitors but not other cytotoxic compounds or targeted agents such as EGFR/MEK inhibitors. Following BEZ235 treatment, acquired resistant clones underwent less cell cycle G1 arrest and displayed greater invasion and migration compared to parental cells. No significant differences were seen in basal levels of pRTKs, pAKT, pmTOR, pS6 and p4EBP1, and apoptosis. In summary, EGFR inhibitor-refractory cells with acquired resistance to PI3K/mTOR inhibition have been generated and characterized with phenotypes suggestive of a class-mediated mechanism of acquired resistance. Possible mediators of acquired resistance have emerged following RNA-sequencing and reverse phase protein array analyses and are currently being validated. Citation Format: King Xin Koh, Bhaskar Bhattacharya, Joanne Loh, Hong Kiat Ng, Ross Soo, Barry Iacopetta, Richie Soong. Determinants of acquired resistance to PI3K/mTOR inhibition in cells refractory to EGFR inhibition. [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 5650. doi:10.1158/1538-7445.AM2013-5650
Clinical Experience with Anticoagulant Therapy During Pregnancy
Authors: J. Hirsh, J. F. Cade, E. F. O'Sullivan
Journal: BMJ (1970)

Fourteen patients were treated with anticoagulants during 15 pregnancies. Eleven had venous thrombosis, three with pulmonary embolism; three had prosthetic heart valves; and one had mitral stenosis with pulmonary hypertension. All 15 were treated with heparin and 10 with warfarin. The mean duration of heparin therapy was 4·5 weeks and of warfarin 14 weeks. There were two minor episodes of recurrent thromboembolism and three minor haemorrhagic episodes during anticoagulant therapy. No fetal or neonatal complications occurred. There appears to be no ideal anticoagulant regimen for treating thromboembolic disease in pregnancy. A compromise approach based on experimental and clinical findings is suggested, which is considered to offer reasonable protection to the mother without undue risk to the fetus. This is heparin when an anticoagulant is indicated in the first trimester, after 37 weeks9 gestation, and for the treatment of the initial thromboembolic episodes. Oral anticoagulants are used at other times when long-term anticoagulant therapy is indicated.
Successful treatment of refractory rheumatoid arthritis-associated leg ulcerations with adalimumab
Authors: D. Hirche, A. Rubbert, L. Lunau, T. Krieg, S.A. Eming
Journal: British Journal of Dermatology (2005)

Conflicts of interest: none declared. Sir, The development of recalcitrant skin ulcerations is a severe complication of rheumatoid arthritis (RA). About 10% of patients with RA will develop painful, therapy‐resistant ulcerations of the lower leg.1 The aetiology of leg ulcers in RA is unclear and clinical studies indicate that most are of multifactorial origin.2 Contributing factors include venous insufficiency, peripheral arterial disease and/or mechanical factors; the role of vasculitis in leg ulceration in RA is controversial. Pyoderma gangrenosum (PG) may occur in association with RA.3 Leg ulcers in RA tend to be resistant to local therapy; treatment often includes the stabilization of the underlying autoimmune disease, e.g. with high doses of glucocorticoids or other potent immunosuppressives. In recent years, excessive tumour necrosis factor (TNF)‐α production has been shown to play a pivotal role in the pathogenesis of RA, and blocking TNF‐α signalling has opened a possible perspective for controlling synovial inflammation and destruction of articular cartilage and bone.4 However, little is known about the effect on cutaneous manifestations of RA of this treatment, specifically on healing of leg ulcerations.
Incomplete Financial Disclosure in a Commentary on Testing for Fragile X Gene Mutations Throughout the Life Span
Authors: Paul J. Hagerman
Journal: JAMA (2009)

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Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction
Authors: Yoshiya Monden, Toru Kubota, Takaki Tsutsumi, Takahiro Inoue, Shunichi Kawano, Natsumi Kawamura, Tomomi Ide, Kensuke Egashira, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Cardiovascular Research (2006)

Tumor necrosis factor (TNF)-alpha induced in damaged myocardium has been considered to be cardiotoxic. However, the negative results of RENEWAL and ATTACH prompt us to reconsider the role of TNF-alpha in cardiovascular diseases. The present study aimed to evaluate the effects of soluble TNF receptor treatment on myocardial infarction (MI).An adenovirus encoding a 55-kDa TNF receptor-IgG fusion protein (AdTNFR1) was used to neutralize TNF-alpha, and an adenovirus encoding LacZ (AdLacZ) served as control. In the pre-MI treatment protocol, mice were given an intravenous injection of AdTNFR1 or AdLacZ 1 week before left coronary artery ligation to induce MI. In the post-MI treatment protocol, mice were treated with AdTNFR1 or AdLacZ 1 week after left coronary ligation.Treatment with AdTNFR1 neutralized bioactivity of TNF-alpha that was activated after MI and prevented apoptosis of infiltrating cells in infarct myocardium. However, pre-MI treatment with AdTNFR1 promoted ventricular rupture by reducing fibrosis with further activation of matrix metalloproteinase (MMP)-9. Post-MI treatment with AdTNFR1 exacerbated ventricular dysfunction and remodeling, with enhanced fibrosis of non-infarct myocardium with further MMP-2 activation.Both pre- and post-MI treatments with AdTNFR1 were deleterious in a mouse MI model. Thus, TNF-alpha may play not only toxic but also protective roles in MI.
Effect of single doses of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the airway response to methacholine.
Authors: D W Cockcroft, V A Swystun
Journal: Thorax (1997)

BACKGROUND: Commercially available salbutamol is a racemic mixture consisting of equal amounts of the two enantiomers, R-salbutamol and S-salbutamol, felt to be active and inert, respectively. METHODS: A double blind, randomised, four way, crossover study was performed in 12 well controlled asthmatic subjects (forced expiratory volume in one second (FEV1) &gt; 70% predicted, no beta 2 agonists for &gt; or = 4 weeks). Subjects were studied on four days at intervals of 48 hours to seven days. FEV1 was assessed before and both FEV1 and methacholine PC20 were measured 20 and 180 minutes after a single dose of nebulised racemic salbutamol 2.5 mg, R-salbutamol 1.25 mg, S-salbutamol 1.25 mg, and placebo. RESULTS: Equivalent bronchodilation was seen for both R-salbutamol and racemic salbutamol (mean (SE) 12.4 (3.1)% and 12.0 (3.0)%, respectively, at 20 minutes and 5.9 (2.9)% and 5.2 (2.2)% at 180 minutes). The increase in FEV1 of 5.2 (0.9)% at 20 minutes and the decline in FEV1 of 2.9 (2.1)% at 180 minutes after S-salbutamol were not significantly different from the placebo response. Compared with placebo the methacholine PC20 after R-salbutamol and racemic salbutamol improved by 3.3 (95% CI 2.5 to 4.1) and 3.4 (95% CI 2.6 to 4.2) doubling doses, respectively, at 20 minutes and 1.2 (95% CI 0.6 to 1.8) and 1.0 (95% CI 0.2 to 1.8) doubling doses at 180 minutes. S-salbutamol resulted in an improvement of 0.9 (95% CI 0.3 to 1.5) doubling doses at 20 minutes and no change at 180 minutes. Restlessness (n = 11) and increased pulse were seen 20 minutes after racemic and R-salbutamol but not S-salbutamol or placebo, and not at 180 minutes. There were no other adverse events. CONCLUSION: A single dose of 1.25 mg nebulised R-salbutamol produced equivalent bronchoprotection, bronchodilation, restlessness, and tachycardia as did 2.5 mg of racemic salbutamol. S-salbutamol 1.25 mg had a weak bronchoprotective effect; this could be because of a small amount of contamination with R-salbutamol or because S-salbutamol is an intrinsically weak beta 2 receptor stimulant.
In Celiac Disease, a Subset of Autoantibodies against Transglutaminase Binds Toll-Like Receptor 4 and Induces Activation of Monocytes
Authors: Giovanna Zanoni, Riccardo Navone, Claudio Lunardi, Giuseppe Tridente, Caterina Bason, Simona Sivori, Ruggero Beri, Marzia Dolcino, Enrico Valletta, Roberto Corrocher, Antonio Puccetti
Journal: PLoS Medicine (2006)

Celiac disease is a small intestine inflammatory disorder with multiple organ involvement, sustained by an inappropriate immune response to dietary gluten. Anti-transglutaminase antibodies are a typical serological marker in patients with active disease, and may disappear during a gluten-free diet treatment. Involvement of infectious agents and innate immunity has been suggested but never proven. Molecular mimicry is one of the mechanisms that links infection and autoimmunity.In our attempt to clarify the pathogenesis of celiac disease, we screened a random peptide library with pooled sera of patients affected by active disease after a pre-screening with the sera of the same patients on a gluten-free diet. We identified a peptide recognized by serum immunoglobulins of patients with active disease, but not by those of patients on a gluten-free diet. This peptide shares homology with the rotavirus major neutralizing protein VP-7 and with the self-antigens tissue transglutaminase, human heat shock protein 60, desmoglein 1, and Toll-like receptor 4. We show that antibodies against the peptide affinity-purified from the sera of patients with active disease recognize the viral product and self-antigens in ELISA and Western blot. These antibodies were able to induce increased epithelial cell permeability evaluated by transepithelial flux of [(3)H] mannitol in the T84 human intestinal epithelial cell line. Finally, the purified antibodies induced monocyte activation upon binding Toll-like receptor 4, evaluated both by surface expression of activation markers and by production of pro-inflammatory cytokines.Our findings show that in active celiac disease, a subset of anti-transglutaminase IgA antibodies recognize the viral protein VP-7, suggesting a possible involvement of rotavirus infection in the pathogenesis of the disease, through a mechanism of molecular mimicry. Moreover, such antibodies recognize self-antigens and are functionally active, able to increase intestinal permeability and induce monocyte activation. We therefore provide evidence for the involvement of innate immunity in the pathogenesis of celiac disease through a previously unknown mechanism of engagement of Toll-like receptor 4.
Tuberculosis in health service staff
Authors: I. S Symington
Journal: BMJ (1985)

The role of platelets in the pathogenesis of migraine, especially in terms of the "protec- tion" offered by diabetes mellitus, is even more perplexing.Activation of platelets, platelet hyperaggregability, and the release of vasoactive substances from platelets have all been incriminated in the pathogenesis of migraine.'Platelets are known to be hyperactive and hyperaggregable in diabetes mellitus and release more thromboxane A2,59 especially when macrovascular disease is concomitantly present.10Yet diabetes mellitus offers protec- tion from migraine.This would suggest that the answer to the diabetic's "protection" from migraine lies not in platelets but in blood vessels themselves.
Why a Little Aspirin Is Better Than a Lot
Authors: Beverly Merz
Journal: JAMA (1987)

WHILE CLINICAL investigators continue their empirical search for the optimum aspirin dose to prevent thrombogenesis, basic researchers have been looking at the effect of aspirin on two prostaglandins that are instrumental in clot formation. Laboratory studies have determined that aspirin inhibits the production of cyclo-oxygenase, an enzyme that is essential for the production of thromboxane (TXA<sub>2</sub>), which promotes platelet aggregation, as well as for the synthesis of prostacyclin (PGI<sub>2</sub>), which inhibits platelet aggregation. Fortunately, aspirin's effects on TXA<sub>2</sub>, which is produced by platelets, are longer lasting. Because platelets are not capable of producing new supplies of cyclo-oxygenase, the resumption of TXA<sub>2</sub>production requires 48 hours— the time it takes to release a new generation of platelets. In contrast, PGI<sub>2</sub>is produced by endothelial cells, which are capable of cyclo-oxygenase production. As soon as aspirin therapy is discontinued, the endothelium resumes cyclo-oxygenase production. As a result,
Recording of diastolic slope from the junctional area in dogs with junctional rhythm.
Authors: R J Hariman, C M Chen
Journal: Circulation (1983)

Stable junctional rhythm was induced in 14 of 25 anesthetized dogs by exclusion of the sinus node and surrounding atrial tissue. In 12 of the 14 dogs diastolic slope was recorded through a unipolar lead consisting of a terminal of a plunge or catheter electrode placed in the His bundle area coupled with an indifferent superior vena caval electrode. Reversed polarity, high-gain amplification (0.1 mV/cm), and low-pass filters (0.1 to 50 Hz) were used for the unipolar recording. The diastolic slope (0.15 +/- 0.07 mV/sec) was recorded from a localized area close to the His bundle and preceded the bipolar His bundle deflection. Overdrive atrial stimulation was followed by slowing of the junctional rate and decrease in the diastolic slope. A strong negative correlation (r values from -.78 to -.95) was found between the junctional cycle lengths and the diastolic slopes after atrial pacing. Isoproterenol infusion increased the junctional rate and the diastolic slope, whereas vagal stimulation and verapamil injection decreased them. The effects of verapamil were partly reversed by CaCl2 injection. The responses of the diastolic slope to overdrive pacing, vagal stimulation, and isoproterenol suggest that the deflection is indeed due to membrane current responsible for phase 4 depolarization. The responses of the junctional rhythm and the diastolic slope to verapamil and CaCl2 suggest that AV nodal automaticity is responsible for the rhythm. Clinical application of this recording technique should help in the identification and characterization of automatic junctional rhythm.