tbuckley/cabot-search huggingface dataset:
Phase I and Pharmacokinetic Study of AI-850, A Novel Microparticle Hydrophobic Drug Delivery System for Paclitaxel
Authors: Alain C. Mita, Anthony J. Olszanski, Richard C. Walovitch, Raymond P. Perez, Kathleen MacKay, David P. Tuck, Cecilia Simmons, Susan Hammond, Monica M. Mita, Muralidhar Beeram, Anne J. Stone, Eric K. Rowinsky, Lionel D. Lewis
Journal: Clinical Cancer Research (2007)

AI-850, paclitaxel in a novel polyoxyethylated castor oil-free hydrophobic microparticle delivery system, is being developed based on its favorable preclinical safety and antitumor activity profiles. The objectives of the study were to assess the feasibility and safety of administering AI-850 as a <30-min i.v. infusion without premedication every 3 weeks, determine the maximum tolerated dose and the phase II recommended dose of AI-850, study the pharmacokinetics of paclitaxel in this new formulation, and seek evidence of anticancer activity.This was an open-label phase I dose escalation study of AI-850 in patients with advanced solid malignancies. AI-850 doses were escalated according to a modified Fibonacci scheme. Clinical and laboratory toxicity was monitored, and paclitaxel plasma concentrations were measured by liquid chromatography-tandem mass spectrometry.Twenty-two patients received 56 courses of AI-850 at five dose cohorts ranging from 36 to 250 mg/m(2). Grade 4 neutropenia, either exceeding 5 days or complicated by fever, was dose limiting in two of six patients at 250 mg/m(2) AI-850. Three patients experienced grade 2 to 4 infusion-related adverse reactions. Toxicities, including fatigue, alopecia, nausea and vomiting, neuropathy, anorexia, and myalgia, were mild to moderate, reversible, and not dose related. Pharmacokinetics of free and total paclitaxel showed biexponential plasma decay and dose proportionality for maximum plasma paclitaxel concentration and area under the concentration versus time curve. Antitumor activity was documented in two patients with endometrial and tongue carcinomas.The administration of AI-850 as a brief infusion once every 3 weeks was feasible at doses up to 205 mg/m(2). The potential of AI-850 as an alternative to other approved paclitaxel formulations requires further clinical evaluation.
Hypoxic apnea and gasping.
Authors: W G Guntheroth, I Kawabori
Journal: Journal of Clinical Investigation (1975)

We have tested the hypothesis that severe lypoxia causes apnea, regardless of the arterial CO2 and pH, and that extreme hypoxia causes gasping. Acute experiments with airway occlusion and with low inspired oxygen (FIo2) were performed on anesthetized adult dogs and monkeys. Arterial oxygen saturation was recorded continuously with fiberoptic oximetry, and Pco2 by an electrode catheter. In addition, blood samples were obtained for Po2, Pco2, and pH. Apnea was induced regularly when the Pao2 fell below 10 torr, whether the Paco2 was high with asphyxia (63 torr) or low (26 torr) with low FIo2. Similarly, the Pao2 at apnea was the same whether the pH was 7.17 with asphyxic hypoxia or 7.46 with hypoxic hypoxia. Gasping occurred at even lower Pao2 (below 5 torr) after 1 or 2 min of apnea. Gasping promptly restored the Pao2 to levels of moderate hypoxia (over 30 torr) which permitted resumption of regular respiration, with gradual elimination of the gasping. Fetal monkeys at term were studied in a similar manner from the moment of cord clamping. Their blood gases with apnea were quite similar to adult values in the narrow range of Pao2 and the wide range of Paco2 and pH. In the fetus, gasping was less immediately effective in improving arterial oxygen, but more persistent than in the adult. Regular respirations would not develop in the absence of oxygen in either the fetus or adult animal.
International Variation in and Factors Associated With Hospital Readmission After Myocardial Infarction
Authors: Robb D. Kociol, Renato D. Lopes, Robert Clare, Laine Thomas, Rajendra H. Mehta, Padma Kaul, Karen S. Pieper, Judith S. Hochman, W. Douglas Weaver, Paul W. Armstrong, Christopher B. Granger, Manesh R. Patel
Journal: JAMA (2012)

ST-segment elevation myocardial infarction (STEMI) treatment has improved outcomes and shortened hospital stay. Recently, 30-day readmission rates have been proposed as a metric for care of patients with STEMI. However, international rates and predictors of 30-day readmission after STEMI have not been studied.To determine international variation in and predictors of 30-day readmission rates after STEMI and country-level care patterns.Post hoc analysis of the Assessment of Pexelizumab in Acute Myocardial Infarction trial that enrolled 5745 patients with STEMI at 296 sites in the United States, Canada, Australia, New Zealand, and 13 European countries from July 13, 2004, to May 11, 2006. Multivariable logistic regression analysis was used to identify independent predictors of all-cause and nonelective 30-day postdischarge readmission.Predictors of 30-day postdischarge all-cause and nonelective readmissions.Of 5571 patients with STEMI who survived to hospital discharge, 631 (11.3%) were readmitted within 30 days. Thirty-day readmission rates were higher for the United States than other countries (14.5% vs 9.9%; P < .001). Median length of stay was shortest for US patients (3 days; interquartile range, 2-4 days) and longest for Germany (8 days; interquartile range, 6-11 days). In multivariable regression, the predictors of 30-day readmission included multivessel disease (odds ratio [OR], 1.97; 95% CI, 1.65-2.35) and US location (OR, 1.68; 95% CI, 1.37-2.07). Excluding elective readmission for revascularization, US enrollment was still an independent predictor of readmission (OR, 1.53; 95% CI, 1.20-1.96). After adjustment of the models for country-level median length of stay, US location was no longer an independent predictor of 30-day all-cause or nonelective readmission. Location in the United States was not a predictor of in-hospital death (OR, 0.88; 95% CI, 0.60-1.30) or 30-day postadmission death (OR, 1.0; 95% CI, 0.72-1.39).In this multinational study, there was variation across countries in 30-day readmission rates after STEMI, with readmission rates higher in the United States than in other countries. However, this difference was greatly attenuated after adjustment for length of stay.
Letter: Endotoxic shock complicating transhepatic cholangiography.
Authors: W I Shedden
Journal: BMJ (1973)

In Scotland similar immunoglobulin is pre- pared at the Protein Fractionation Gentre and can be obtained by contacting the director of the appropxiate regional blood transfusion centre who will also provide information re- garding the local follow-up arrangements for the recipient.-Iam, etc.,
The Anti-Nostrum War Is Right.
Authors: William Porter.
Journal: JAMA (1906)

Saint Louis, Sept. 10, 1906. <h3>To the Editor:</h3> —Just a word to express my endorsement of your editorial September 8. When I compare present conditions with what we have had a few years ago, the better organization, the increased<i>esprit de corps</i>, the local interest, the aggressive nostrum war and the "mute but eloquent" proof which comes to us with every issue ofThe Journal, I would be false to my ideas of right did I not express my appreciation. The policy ofThe Journaltoward the "patent-medicine" interests and those who support them is right. Its campaign in effecting local organizations and in building up state associations is right. Its successful work in giving us the best and most complete presentation of literature which we need each week is right, I know I am the better, the A. M. A. better, andThe Journalbetter and more prosperous than
Rapid Clearance of Perfusion Defects in a Patient With Suspected Pulmonary Embolism
Authors: ZOHAR KEIDAR, ORON EILAM
Journal: Clinical Nuclear Medicine (1998)

Pulmonary embolism was suspected in a 38-year-old schizophrenic man who was admitted because of acute shortness of breath. Perfusion lung imaging demonstrated large segmental perfusion defects with matched ventilation abnormalities. A detailed history was taken and revealed an episode of aspiration hours earlier. A repeat perfusion lung scan 48 hours later was normal. Vasoconstriction due to alveolar hypoxia probably caused the perfusion defects.
Thomas Hugh Willson
Authors: R. Luder
Journal: BMJ (2014)

Thomas Hugh Willson (“Tom”) attended St Albans School before going up to Queen’s College, Oxford, to study zoology in 1976, obtaining a 2nd. He subsequently funded himself through medical school, playing guinea pig in many medical trials.

After finishing house jobs in St Albans and Barnet, he completed GP training, and obtained a principal’s position at Burvill House Surgery in Hatfield. One of his first tasks was to try to referee a difficult negotiation between the …
Continuing Disparities in Cardiovascular Risk Factors and Complications Between Aboriginal and Anglo-Celt Australians With Type 2 Diabetes
Authors: Timothy M.E. Davis, Kerry Hunt, Daniel McAullay, Stephen A.P. Chubb, Brett A. Sillars, David G. Bruce, Wendy A. Davis
Journal: Diabetes Care (2012)

To determine whether disparities in the nature and management of type 2 diabetes persist between Aboriginal and the majority Anglo-Celt patients in an urban Australian community.
Renal Trauma in Childhood
Authors: Lester Persky
Journal: JAMA (1962)

A review of the clinical course of 65 children who had renal trauma has been carried out. The largest percentage of such injuries occurred in the age group 10-14 and were seen after falls or automobile accidents. Of the injuries, 74% were classified as contusions and needed only conservative management. Fifteen patients were found to have preexisting renal disease. Hydronephrotic kidneys constituted the largest share of these. Two patients had ruptured teratoma of the renal cortex (Wilms' tumor). The high incidence of such renal abnormalities clearly indicates the need for complete urological investigation, no matter how trivial the injury appears, or how slight the attendant hematuria or discomfort.
From the Office of Technology Assessment
Authors: R. Y. Nishimi
Journal: JAMA (1993)

In response to Congressional requests that it study the implications of the wide-spread use of DNA-based CF (cystic fibrosis) carrier tests, the Office of Technology Assessment published the report Cystic Fibrosis and DNA Tests: Implications of Carrier Screening (Washington: OTA; 1992). This article briefly summarizes the report's conclusions.
Psoriatic arthritis and imaging
Authors: P A Ory, D D Gladman, P J Mease
Journal: Annals of the Rheumatic Diseases (2005)

Psoriatic arthritis (PsA) has historically been considered a milder rheumatic disease not yielding significant clinical damage. However, recent studies have shown that PsA can be deforming and debilitating and that joint damage can be severe. Traditionally, joint damage has been recorded using plain radiographs. Characteristic radiographic features of PsA include joint erosions, joint space narrowing, bony proliferation including periarticular and shaft periostitis, osteolysis including "pencil in cup" deformity and acro-osteolysis, ankylosis, spur formation, and spondylitis. New imaging modalities, including ultrasound, bone scanning, and magnetic resonance imaging may help in both diagnosis and follow up of patients with PsA. These new imaging techniques will with validation help detect early changes in the peripheral joints, the periarticular tissues, and the spinal structures in patients with PsA.
NHS gets 4% more funding a year until 2011—but spend it wisely, says BMA
Authors: Helen Mooney
Journal: BMJ (2007)

The NHS in England and Wales has been given a 4% a year funding rise for the next three years, with an overall budget rise from £90bn this year to £110bn in 2010.

Announcing the comprehensive spending review, the chancellor, Alistair Darling, said that the cash would fund 20 new hospitals, 140 walk-in centres open seven days a week, and 100 new GP practices.

However, the funding is much less than the 7.2% that the NHS has had each year since 2002 and below the 4.4% recommended by Derek Wanless in his review of the future of the NHS published in …
Treatment of hemophilic arthritis with D‐penicillamine: A preliminary report
Authors: James J. Corrigan, Karen S. Kolba, Eric P. Gall, Joyce Trombley, Mary Lou Damiano, Keith Meredith, Monette Jeter
Journal: American Journal of Hematology (1985)

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline-injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild-moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.
From America: manpower, money, and cookbook medicine.
Authors: M H Liang
Journal: Annals of the Rheumatic Diseases (1991)

Aims: The molecular mechanisms of triptolide responsible for its antitumor properties are not yet fully understood. The ubiquitin/proteasome system is an important pathway of protein degradation in cells. This study investigated whether triptolide may inhibit proteasomal activity and induce apoptosis in human cancer cells. Materials and Methods: In vitro proteasome inhibition was measured by incubation of a purified 20S proteasome with triptolide. Human breast and prostate cancer cell lines were also treated with different doses of triptolide for different times, followed by measurement of proteasome inhibition (levels of the chymotrypsin-like activity, ubiquitinated proteins and three well-known proteasome target proteins, p27, IκB-α and Bax) and apoptosis induction (caspase-3 activity and PARP cleavage). Results: Triptolide did not inhibit the chymotrypsin-like activity of purified 20S proteasome. However, treatment of triptolide was able to cause decreased levels of cellular proteasomal chymotrypsin-like activity and accumulation of ubiquitinated proteins and three well-known proteasome target proteins in human breast and prostate cancer cells, associated with apoptosis induction. Conclusion: It is possible that at least one of metabolites of triptolide has proteasome-inhibitory activity.
SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance
Authors: Lei Cai, Ailing Ji, Frederick C. de Beer, Lisa R. Tannock, Deneys R. van der Westhuyzen
Journal: Journal of Clinical Investigation (2008)

Septic shock results from an uncontrolled inflammatory response, mediated primarily by LPS. Cholesterol transport plays an important role in the host response to LPS, as LPS is neutralized by lipoproteins and adrenal cholesterol uptake is required for antiinflammatory glucocorticoid synthesis. In this study, we show that scavenger receptor B-I (SR-BI), an HDL receptor that mediates HDL cholesterol ester uptake into cells, is required for the normal antiinflammatory response to LPS-induced endotoxic shock. Despite elevated plasma HDL levels, SR-BI–null mice displayed an uncontrollable inflammatory cytokine response and a markedly higher lethality rate than control mice in response to LPS. In addition, SR-BI–null mice showed a lack of inducible glucocorticoid synthesis in response to LPS, bacterial infection, stress, or ACTH. Glucocorticoid insufficiency in SR-BI–null mice was due to primary adrenal malfunction resulting from deficient cholesterol delivery from HDL. Furthermore, corticosterone supplementation decreased the sensitivity of SR-BI–null mice to LPS. Plasma from control and SR-BI–null mice exhibited a similar ability to neutralize LPS, whereas SR-BI–null mice showed decreased plasma clearance of LPS into the liver and hepatocytes compared with normal mice. We conclude that SR-BI in mice is required for the antiinflammatory response to LPS-induced endotoxic shock, likely through its essential role in facilitating glucocorticoid production and LPS hepatic clearance.
Clinical Research in the Acquired Immunodeficiency Syndrome
Authors: William G. Powderly
Journal: Annals of Internal Medicine (1995)

Editorials1 February 1995Clinical Research in the Acquired Immunodeficiency SyndromeWilliam G. Powderly, MD, FRCPIWilliam G. Powderly, MD, FRCPISearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-3-199502010-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Anniversaries tend to be occasions for reflection, for review of past accomplishments and disappointments, and for renewal of aspirations. Therefore, it is not surprising that approximately 10 years after the discovery that the human immunodeficiency virus (HIV) causes the acquired immunodeficiency syndrome (AIDS), much discussion of the progress made in AIDS research has taken place and many proposals to completely overhaul our approach to this problem have been made [1].Clearly, this is not a time for celebration. That the progress made to date has been insufficient is plainly evident in most of our hospitals every day. The acquired immunodeficiency ...References1. Fields BN. AIDS: time to turn to basic science. Nature. 1994; 369:95-6. Google Scholar2. Centers for Disease Control. Update: mortality attributable to HIV infection among persons aged 25-44 years-United States, 1991 and 1992. MMWR Morb Mortal Wkly Rep. 1993; 42:869-72. Google Scholar3. Osmond D, Charlebois E, Lang W, Shiboski S, Moss A. Changes in AIDS survival time in two San Francisco cohorts of homosexual men, 1983 to 1993. JAMA. 1994; 271:1083-7. Google Scholar4. Centers for Disease Control. Zidovudine for the prevention of HIV transmission from mother to infant. MMWR Morb Mortal Wkly Rep. 1993; 43:285-7. Google Scholar5. Lederman MM. Host-directed and immune-based therapies for HIV infection. Ann Intern Med. 1995; 122:218-222. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHost-Directed and Immune-Based Therapies for Human Immunodeficiency Virus Infection Michael M. Lederman Metrics Cited ByThe importance of the family in patient education and care 1 February 1995Volume 122, Issue 3Page: 232-233KeywordsAIDSAntiviral therapyAntiviralsBiomarkersClinical trialsDrugsHIVHIV infectionsInfectious diseasesPathogenesis Issue Published: 1 February 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
C3-04: Phase III study comparing a preoperative (PRE) and a perioperative (PERI) chemotherapy (CT) with two different CT regimens in resectable stage I-II non-small cell lung cancer (NSCLC): the IFCT 0002 protocol
Authors: Alain Depierre, Bernard Milleron, Elisabeth Quoix, Marc Puyraveau, Denis Braun, Jean-Luc Breton, Laurence Bigay-Game, Jean-Louis Pujol, Franck Morin, Virginie Westeel
Journal: Journal of Thoracic Oncology (2007)
Heinz‐body anemia: “Bite Cell” variant— A light and electron microscopic study
Authors: Patrick C. J. Ward, Burton S. Schwartz, James G. White
Journal: American Journal of Hematology (1983)

Abstract Light and scanning electron microscopic studies of blood from five patients with drug‐induced oxidant hemolysis are presented. None of the patients had a previous history of hemolytic disease and laboratory studies indicated no evidence of either glucose‐6‐phosphate dehydrogenase (G6PD) deficiency or unstable hemoglobinopathy. Although the red cell deformities in our patients overlapped to some extent with those reported in patients with microangiopathic hemolytic anemia (MAHA) and in patients with G6PD deficiency undergoing oxidant hemolysis, striking differences were also observed. Cell fragments, commonly found in patients with MAHA, and eccentrocytes, frequently found in patients with G6PD deficiency undergoing oxidant hemolysis, were seldom found in blood samples from the five patients in this study. Bite cells were extremely common in our patients. They are rare in patients with either of the above disorders. An awareness of the morphologic abnormalities detailed in this report may help characterize the nature of a hemolytic process so that appropriate therapy can be initiated.
Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity.
Authors: J F Caro, O Ittoop, W J Pories, D Meelheim, E G Flickinger, F Thomas, M Jenquin, J F Silverman, P G Khazanie, M K Sinha
Journal: Journal of Clinical Investigation (1986)

We have developed a method to isolate insulin-responsive human hepatocytes from an intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from obese patients with noninsulin-dependent diabetes were resistant to maximal insulin concentration, and those from obese controls to submaximal insulin concentration in comparison to nonobese controls. Insulin binding per cell number was similar in all groups. However, insulin binding per surface area was decreased in the two obese groups because their hepatocytes were larger. In addition, the pool of detergent-extractable receptor was further decreased in diabetics. Insulin receptors in all groups were unaltered as determined by affinity-labeling methods. However, insulin-stimulated insulin receptor kinase activity was decreased in diabetics. Thus, in obesity, decreased surface binding could explain resistance to submaximal insulin concentrations. In diabetes, diminished insulin-stimulated protein kinase activity and decreased intracellular pool of receptors could provide an explanation for postinsulin-binding defect(s) of insulin action in human liver.
Coxsackie Viruses and Diabetes Mellitus
Authors: D. R. Gamble, K. W. Taylor, H. Cumming
Journal: BMJ (1973)

Serum specimens from 162 patients with insulin-dependent diabetes of recent onset and 319 controls were tested for neutralizing antibodies to Coxsackie viruses types B1 to B5. Antibody to type B4 virus was more often found in diabetics than in controls, particularly in the 10-19 year age group. Though controls were not matched for geographical area it was thought that this was unlikely to explain the difference found. The month of onset of diabetes in the patients studied showed a pronounced seasonal incidence, which resembled that found in earlier studies.