tbuckley/cabot-search huggingface dataset:
Revalidation in the United Kingdom
Authors: P. Furness
Journal: BMJ (2000)

Editor—Scanning the contents of the BMJ for 30 October 1999, I thought I detected an editorial masterstroke. The education and debate section contained five articles on revalidation,1 followed by—here's the flash of inspiration—an article on the problems of medical staffing in our hospitals.2

Sadly, this seems to have been pure serendipity. Far from “debate,” the authors all seemed blissfully unaware of any link. Article followed article on revalidation, describing teams of doctors, busily revalidating teams of doctors. In apparent isolation, the last article discussed the staffing crisis without mention of the workload to be imposed by revalidation.

I do not question the need for revalidation, but I do question the practicality of implementing these plans without new resources and more staff. There was not even an assessment of the cost, let alone a cost benefit analysis.

Would it not be a good idea, in a section labelled “debate,” to have at least one author who questions the dogma?
Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump.
Authors: G R Weiss, M B Garnick, R T Osteen, G D Steele, R E Wilson, D Schade, W D Kaplan, L M Boxt, K Kandarpa, R J Mayer
Journal: Journal of Clinical Oncology (1983)

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.
Abstract 316: Cell-Matrix Contacts Regulate Age-Associated Cardiac Function
Authors: Ayla O Sessions, Gaurav Kaushik, Anthony Cammarato, Adam Engler
Journal: Circulation Research (2014)

An increased deposition of ECM is observed in all advanced age heart failure patients. Therefore, it is necessary to investigate the effect of extracellular remodeling on mechanical function in genetically tractable, rapidly aging, and simple model organisms such as Drosophila melanogaster . The bilayered design of the Drosophila heart-tube makes it an easier model in which to study the interplay between ECM and cardiomyocytes as they regulate contraction. Here we present data from two common wildtype strains of Drosophila exhibiting different aging profiles in terms of cytoskeletal and ECM regulation and remodeling. Using a recently developed nanoindentation method to measure cardiomyocyte stiffness of intact Drosophila hearts, we have found that while yellow-white ( yw ) flies show midline stiffening at the intercalated discs (ICD) presenting a clear diastolic dysfunction with age, the white-1118 ( w1118 ) flies exhibit no ICD stiffening, but show an increase in thickness of the ECM layer between the ventral muscle (VM) and cardiomyocytes (CM). Paired with increased expression of ECM proteins, the w1118 Drosophila line may provide a good model for exploring the effect of cell-ECM contacts on regulating cardiac function with age. Knock-down of integral ECM genes LamininA and Viking (Collagen IV) result in no effect on cardiac performance in juvenile flies but causes a decrease in underlying cardiomyocyte stiffness and an increase in the contractile irregularity of heart beats. This suggests that the cell-ECM contacts in the basement membrane are intimately tied to coupling of the cardiomyocytes of the Drosophila heart-tube, which may have larger implications for elderly patients suffering from myocardial fibrosis and experiencing cardiomyocyte decoupling and resultant arrhythmias.
LSC 2013 abstract - A comparative analysis of bacterial phylotypes of the lung microbiota of healthy, IPF and transplanted lungs
Authors: John Erb-Downward, Robert Dickson, MeiLan Han, Christine Freeman, Zachary Britt, Natalie Walker, Vibha Lama, Jeffery Curtis, Fernando Martinez, Gary Huffnagle
Journal: European Respiratory Journal (2013)

Rationale:  Culture-independent microbiology has identified a microbiota in the lungs of both healthy and diseased individuals, which may provide novel insights into the progression of lung disease.   Methods:  Bronchoalveolar lavage (BAL) samples (26 healthy, 44 lung transplant and 78 IPF) were obtained for microbiome analysis by 454-pyrosequencing the V5-V3 region of the bacterial 16S rRNA gene. The software package mothur was used to process, cluster and assign sequences to phylotyped operational taxonomic units (OTUs). Community analysis was carried out in R using the R-package vegan.   Results:  Bacterial communities were visualized by ordination and clusters identified, based on sample type. The lung microbiota of IPF patients and that of transplanted lungs was significantly different from normal lungs (p = 0.001). A non-linear multidimensional scaling of the data demonstrated that the IPF samples could also be broken up into two groups: one that overlapped with the healthy controls and one distinct group. Analysis of the dominant OTUs in each population demonstrated that the lung community of healthy controls, and the overlapping IPF subgroup, was dominated by the genera  Prevotella  and  Veillonella .The other IPF subgroup was dominated by the genera  Pseudomonas, Clostridium XI  group,  Prevotella  and  Flavobacterium . The community of the transplant group was dominated by the genera  Pseudomonas ,  Prevotella  and  Escherichia .   Conclusions:  The lung microbiota of IPF patients and lung transplants is significantly different than the lung microbiota of healthy controls.
Interstitial Lung Disease
Authors: RENUKA UPPALURI, ERIC A. HOFFMAN, MILAN SONKA, GARY W. HUNNINGHAKE, GEOFFREY McLENNAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We have previously described an adaptive multiple feature method (AMFM) for the objective assessment of global and regional changes in pulmonary parenchyma to detect emphysema. This computerized method uses a combination of statistical and fractal texture features for characterization of lung tissues based upon high resolution computed tomography (HRCT) scans. This present study was a substantial extension of the AMFM to simultaneously discriminate between multiple pulmonary disease processes. Normal subjects and those with emphysema, idiopathic pulmonary fibrosis (IPF), or sarcoidosis were studied. The AMFM was compared with two currently utilized computer-based methods: mean lung density (MLD) and the histogram analysis (HIST). Globally, when comparing two-subject groups the AMFM overall accuracy was 2 to 18% better than the overall accuracy of MLD and as much as 36% better than the accuracy of the HIST methods. In three-subject group discrimination tasks, the AMFM performed 7 to 27% better than the MLD and 4 to 36% better than the HIST methods. Finally, in discriminating all four subject groups at a time, the AMFM overall accuracy was 81%, which was 21% better than the MLD and 25% better than the HIST method. In most three-subject group comparisons and in the four-subject group comparison, the AMFM was significantly (p < 0.01) better than the MLD and HIST methods. Next, the AMFM was applied to local discrimination between normal and each disease group individually. The normal versus emphysema, normal versus IPF, and normal versus sarcoidosis samples were discriminated with an accuracy of 95, 86, and 77%, respectively. The AMFM is an objective quantitative method that can be adapted for successful discrimination of multiple parenchymal lung diseases.
Origin and Migration of Huntington's Chorea in Canada: Preliminary Report
Authors: A BARBEAU, G FULLUM
Journal: JAMA (1963)

This preliminary report is part of a fullscale investigation of Huntington's chorea throughout the world. Data were obtained on some 820 possible cases of Huntington's chorea in Canada, and they were of sufficient quality in 633 cases to enable pedigrees to be drawn up of 104 families. The origin of 75 of these families was traced outside Canada. It was found that 55 of these kinships originally came from the British Isles, contrary to the prevalent feeling that incriminated United States sources. Only 57 of the 633 cases had moved from their first province of residence at the time of reporting. Thus, large and frequent migrations are not the rule, in the Canadian group, as had been previously reported by other authors.
Pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) in combination in the salvage treatment of epithelial ovarian cancer (OC)—a Danish Gynaecologic Cancer Group (DGC) study
Authors: M. R. Mirza, B. Lund, K. Bertelsen, J. Lindegaard, N. Keldsen, A. Mellemgaard, R. Depont
Journal: Journal of Clinical Oncology (2006)

5094 Background: Ovarian cancer patients (pts) recurring with a short treatment-free interval (TFI) after prior chemotherapy (PCT) have a bad prognosis. DGC has conducted a phase II study of PLD-GEM in combination in OC pts recurring with a TFI of less than 12 months (mo). Methods: All pts must have received at least one platinum-paclitaxel containing regimen; no PCT with GEM or anthracyclines. Regimen: GEM 800mg/m 2 day 1+8 and PLD 25mg/m 2 day 1, q 21 days. GEM dose escalation to 1g/m 2 day 1+8 from 2. cycle in the absence of grade 3–4 toxicity. Primary end point: OS, secondary: PFS, response and toxicity. Pts were grouped according to their response to PCT. Group 1: pts with CR on PCT and TFI 3–12 mo; group 2: pts with CR on PCT and TFI 0–3 mo; group 3: pts with PR/SD on PCT and TFI 0–12 mo. 35 pts with ≥2 prior number of treatments. Results: 82 pts were enrolled (May 2003-Aug 2005); the median age was 59 yrs (range 31 to 77 yrs); 15 pts were entered with rising CA125 only (GCIG criteria). Groups according to their response to PCT: group 1: 44 pts; group 2: 5 pts; group 3: 33 pts. TFI ≤ 6 mo 33 pts, TFI &gt; 6 to ≤ 12 mo 49 pts. To date data on 330 cycles (mean 4.7 cycles) is available; 45 pts are evaluable for PFS and OS; 62 pts are evaluable for response and 71 pts for toxicity. Grade 3–4 toxicity: PPE 6/330 cycles; mucosites 8/330 cycles; febrile neutropenia 4%; treatment delay 9%. No dose reductions performed for PLD. GEM dose escalation to 1000 mg/m 2 in 31 pts; dose reduction to 650 mg/m 2 at any time in 21 pts; skipped dose day 8 in 44 cycles. Response (RESIST): CR 3 pts; PR 17 pts (CR+PR 32%); SD 39 pts; PD 2 pts. Median PFS 212 days, Median OS 234 days. Conclusions: PLD-GEM in combination in the salvage setting is well tolerated, with acceptable toxicity and clear activity. No significant financial relationships to disclose.
Carboplatin and paclitaxel in ovarian carcinoma: a phase I study of the Gynecologic Oncology Group.
Authors: M A Bookman, W P McGuire, D Kilpatrick, E Keenan, W M Hogan, S W Johnson, P O'Dwyer, E Rowinsky, H H Gallion, R F Ozols
Journal: Journal of Clinical Oncology (1996)

PURPOSE To develop a tolerable, dose-intense regimen of carboplatin and paclitaxel for the treatment of primary epithelial ovarian carcinoma. PATIENTS AND METHODS Patients underwent initial surgical assessment and tumor debulking. Patients with stage III/IV disease received six cycles of chemotherapy on a planned 21-day cycle. Carboplatin dose was calculated based on projected area under the curve (AUC) for concentration over time (mg. mL-1.min) and escalated to determine the maximum-tolerated dose (MTD). Paclitaxel dose was also escalated as a 3-, 24-, or 96-hour infusion. Granulocyte colony-stimulating factors (G-CSFs) were required at selected dose levels or could be added based on hematologic toxicity. RESULTS Thirty-nine patients were enrolled and assessable for toxicity and response. Dose-limiting toxicity (DLT) was hematologic, primarily neutropenia. Less than 2% of all cycles with paclitaxel as a 3- or 24-hour infusion were associated with either grade 4 thrombocytopenia or febrile neutropenia. The carboplatin MTD was AUC 7.5 (equivalent to a median dose of 471 mg/m2). The MTD for paclitaxel was 135 mg/m2 over 24 hours and 175 mg/m2 over 3 hours without initial G-CSF. A 96-hour infusion of paclitaxel at a dose of 120 mg/m2 was associated with excessive single-cycle and cumulative myelosuppression, and was not further evaluated. Measured carboplatin AUC agreed well with the calculated AUC. The overall complete (n = 16) and partial (n = 2) response rate among 24 patients with measurable disease was 75%, with a median progression-free survival time of 15 months. CONCLUSION Carboplatin could be safely combined with paclitaxel using a dose formula based on projected renal clearance. The recommended outpatient regimen is carboplatin AUC 7.5 and paclitaxel 175 mg/m2 over 3 hours without initial G-CSF. This treatment safely achieved a greater dose-intensity of carboplatin than would have been achieved with conventional dosing based on body-surface area.
Controlled asthma in atopic and non atopic patients: Is needed a different approach?
Authors: Angelo Petroianni, Vittoria Conti, Valentina Giunta, Michela Lagalla, Marianna Lilli, Ambra Castagnacci, Augusto Bevilacqua, Safia Khan Kalil, Claudio Terzano
Journal: European Respiratory Journal (2011)

Background: Allergy is a significant trigger for asthmatic exacerbation. Currently, the control of asthma is mainly based on the absence of symptoms and airway obstruction  Aim: To evaluate the difference in atopic (AT) and non atopic (N-AT) patients with controlled asthma on the risk of exacerbation and step up therapy.  Methods: 98 asthmatic pts with ACT (Asthma Control Test) >20 were enrolled in a 3yrs controlled randomized trial. Pts were divided in 2 groups: Group A (ICS) receiving a continuous treatment with inhaled beclomethasone MDI100mcg twice/die +inhaled salbutamol as needed; Group B (control) treated with inhaled salbutamol as needed. Step up therapy was performed as recommended by guidelines. Prick tests for the most common allergens were performed at the enrolment. Primary endpoint were: exacerbations/3mths, ACTscore, and drug as needed  Results: 80 pts (A39,B41) concluded the study; atopic pts were in A 29 (74%), in B 27 (66%). In Group A no significant difference was reported for exacerbations (AT4.2, N-AT3.9) and ACT (AT19.8, N-AT20.4), whereas in Group B slight significant differences reported for exacerbations (AT4.8*, N-AT3.9) and ACT (AT18.6*, N-AT20.1). Interestingly, analyzing data in multisensitized (≥ 3 classes of allergens) and lowsensitized (  Conclusion: Pts with controlled asthma and atopy show a protective effect on exacerbations during a long term treatment with low dosage ICS. Moreover, multisensitized pts with controlled asthma report an high risk of exacerbation than non atopic.
Renal Adaptation to a Low Phosphate Diet in Rats
Authors: Sudhir V. Shah, Stephen A. Kempson, Thomas E. Northrup, Thomas P. Dousa
Journal: Journal of Clinical Investigation (1979)

The major renal adaptive changes in response to selective dietary phosphate restriction are a marked reduction in urinary excretion of phosphate and an increased urinary excretion of calcium; at the cellular level, there is selective increase in renal cortical brush border membrane phosphate uptake and increase in specific activity of alkaline phosphatase. In the present study we examined whether these functional and biochemical adaptive changes could be blocked by drugs known to inhibit protein synthesis.
Long-lasting interaction study between RPL554 and glycopyrronium bromide on human isolated bronchi
Authors: Luigino Calzetta, Mario Cazzola, Clive Page, Paola Rogliani, Francesco Facciolo, Maria Gabriella Matera
Journal: European Respiratory Journal (2014)

Background : The acute relaxant synergistic interaction between RPL554 and anticholinergic agents has been recently proved on human isolated bronchi (Calzetta, L. et al. J Pharmacol Exp Ther. 2013; 346:414-23).

Aim : To investigate the long-lasting interaction between RPL554 and glycopyrronium in human isolated bronchi.

Methods : Bronchial rings from 6 patients were incubated in Krebs-Henseleit solution (37°C) aerated with O2/CO2 (95/5%) under 0.5–1.0 g tension. The duration of action (30% maximal relaxation, EC30) of RPL554 and glycopyrronium, alone or in combination, was studied in tissue contracted with 3-10-25 Hz electrical field stimulation (EFS). Bronchial tone was expressed as % of maximal response to papaverine (Emax) and the area under the curve (AUC) of the contractile response was assessed. Drug mixture effects were analyzed by Bliss Independence theory. Values (n=3) are mean±SEM.

Results : RPL554 and glycopyrronium administered alone induced the maximal relaxation at 160±20 min and 50±10 min, respectively, and the effect was detectable for 4 hrs. The maximal synergistic relaxant interaction was at ≅2 hrs (71.4±5.1%), during the washout period, and the combination of drugs extended the relaxant effect at 6 hrs, when the reduction of EFS-mediated contractile response was still 41.2±8.5%. The observed AUC (44.9±3.1%) was significantly lower than that expected (65.8±3.3%) during the 6 hrs of the study (P<0.001), with the main effectiveness for EFS at 3Hz (-35.8±2.5%, P<0.001).

Conclusions : RPL554 and glycopyrronium at low concentrations synergistically inhibited the contractile tone induced by EFS in human isolated bronchi and extended the ralaxant effect for 6 hrs.
New Guidelines for Breast Cancer Screening in US Women
Authors: Nancy L. Keating, Lydia E. Pace
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Significance of Lymphocyte Fluorescence Polarization Changes After Phytohemagglutinin Stimulation in Cancer and Noncancer Conditions&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J M Rolland, R C Nairn, A P Nind, E Pihl
Journal: JNCI Journal of the National Cancer Institute (1984)

The double-zone fluorescein fluorescence polarization (FFP) "cancer" test was used to study 540 blood lymphocyte samples from 341 donors, of whom 158 had confirmed cancer: The other donors were noncancer patients, pregnant women, and normal individuals. The FFP response in cancer patients was the reverse of that in normal individuals, but an abnormal response was also obtained in some noncancer conditions, including the chronic inflammatory disorders--rheumatoid arthritis, cholecystitis, and diverticulitis--and in early pregnancy or pregnancy-induced hypertension. Thus the cancer discriminatory value of the test is limited. Examination of its biologic basis suggests that the positive FFP response in cancer and other conditions is due to altered immune status of blood lymphocytes, with associated change in cytoplasmic fluidity affecting the polarization of fluorescence. Incubation of normal blood lymphocytes with cyclic GMP induced an abnormal, cancer-like FFP response.
The STOP questionnaire is the best screener for obstructive sleep apnoea syndrome at the sleep clinic
Authors: Keshaf Sharma, Imran Sulaiman, Melissa McDonnell, Akke Vellinga, J.J. Gilmartin
Journal: European Respiratory Journal (2011)

It is important to correctly identify high risk Obstructive Sleep Apnoea Syndrome (OSAS) patients to minimize costs. The gold standard for the diagnosis of OSAS remains polysomnography (PSG), but is resource intensive and with restricted availability. We therefore performed a pilot study to compare the  Epworth, Berlin, STOP and STOPBANG  questionnaires in their ability to identify OSAS confirmed by PSG among high risk patients. Additionally, cut off points to improve clinical prediction of OSAS were explored.   Results:  To date a total of 56 patients have complete data. Their mean BMI was 35.7 (±7.9), collar size 43.5 cm (±4.2) and 35 (63%) were male. Based on an AHI ≥ 15, 31 (55%) were diagnosed with significant OSAS.Those with OSAS had significantly higher BMI as well as collar size. The Epworth questionnaire (cut off 10) had a sensitivity of 77% and specificity of 52%, the Berlin 97% and 24% respectively, STOP 100% and 28%; and STOPBANG 100% and 12%.   Conclusions:  If only patients with high risk scores were selected for subsequent PSG, 59% (Epworth), 13% (Berlin), 86% (STOP) and 93% (STOPBANG) of the patients would be tested. The STOP questionnaire resulted in the best sensitivity/specificity combination (if false negatives are unacceptable) but this would mean that 86% of the patients would have PSG but only 55% would have OSAS. No other combination of factors was found to improve specificity without a considerable decrease in sensitivity.   STOP  is the simplest and most effective screening questionnaire to identify patients with OSAS and could reduce the need for PSG by 14%. A larger cohort is needed to confirm these findings and improve specificity of the questionnaires.
Two sodium channels contribute to the TTX-R sodium current in primary sensory neurons
Authors: Simon Tate, Susanna Benn, Caroline Hick, Derek Trezise, Victoria John, Richard J. Mannion, Michael Costigan, Chris Plumpton, David Grose, Zoe Gladwell, Giles Kendall, Katie Dale, Chas Bountra, Clifford J. Woolf
Journal: Nature Neuroscience (1998)