tbuckley/cabot-search huggingface dataset:
Abstract 2766: Multicenter pharmacokinetic evaluation of ON 01910. Na, a novel broad-spectrum anticancer agent, in Phase I single agent clinical trials in patients with solid tumors
Authors: Manoj Maniar, Sridhar Mani, Mohammed H. Ghalib, John Roboz, Takao Ohnuma, Suresh Advani, Raghunadh Rao, D Doval, Manmohan Acharya, Edward O'Rourke, Francois Wilhelm, James F. Holland, David Taft
Journal: Cancer Research (2010)

Abstract Introduction: ON 01910. Na is an anti-cancer agent with demonstrated activity against both solid tumors and hematological cancers. The purpose of this research was to evaluate the effect of dose and administration schedule on ON 01910. Na pharmacokinetics (PK) in advanced, heavily pre-treated solid tumor patients. Methods: Data was collected in three Phase I protcols conducted in the US and in India covering a wide range of doses and intraveous infusion schedules: Protocol 1 (50-1375 mg/m2/day over 72 h); Protocol 2 (250 – 4450 mg/m2/day over 24 h) and Protocol 3 (2400-3200 mg over 2, 4 or 8 h). In several patients, pharmacokinetics were evaluated for more than 1 dosing cycle. Plasma samples were collected pre-dose and up to 72 hours post-infusion. ON 01910. Na plasma levels were determined by a validated LC/MS/MS method. Results: Ninety-five data sets from 81 patients were evaluated in this study. ON 01910. Na showed biphasic elimination from the plasma, regardless of dose and administration schedule. The functional half-life of ON 01910. Na, estimated from the initial decline of plasma levels following infusion termination, was less than 2 hours. This was confirmed in data from patients receiving prolonged infusions as ON. 01910. Na approached steady state levels within several hours after dose initiation. As noted in the table below, ON. 01910. Na clearance was lower at higher drug dosing rates. There were no differences in drug pharmacokinetics among the infusion schedules. Conclusion: The pharmacokinetics of ON 01910. Na is dose dependent. A continuous IV infusion would be recommended to treat patients because of its short plasma half-life and rapid clearance. Systemic drug exposure is not affected by type of dosing (flat dosing vs. BSA adjusted). No significant differences were noted between the PK profiles of patients in the US centers and the patients in the India centers.Effect of Dosing Rate on Clearance of ON 01910. NaDosing Rate (mg/m2/hr)NClearance (L/hr/m2)0-25189.3 ± 4.725-501610.0 ± 5.050-75209.2 ± 3.175-10065.5 ± 2.6100-200126.2 ± 3.8200-40083.3 ± 1.6400-800112.5 ± 1.8800-125041.9 +/− 0.47 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2766.
The quest for transparency
Authors: Imre Loefler
Journal: BMJ (2005)

The concept of transparency as an ideal state is not limited to political and business morality. By making our bodies transparent, the first indications of structural failure and malfunction can be detected at molecular level and problems can be remedied.

The body can be made transparent by tests, analysis, and imaging. Clearly, knowledge of the finest details of one's macro- and micro-anatomy and physiology, including …
Doing the kind thing
Authors: Chris Burns-Cox, Rachel Gilbert
Journal: BMJ (2005)

Our results are supported by earlier research on acupuncture for low back pain. 16 17 A combination of several methods for treating pelvic girdle pain in pregnancy is probably better than individual treatments Each method needs to be evaluated individually, however, before combinations can be recommended for future research and treatment.We thank physiotherapists E Roos-Hansson and G Zetherstrom for invaluable help with assessment of the patients.We thank physiotherapists T Larsson and K Wettergren and midwife K Frygner for treating the patients.We also express our appreciation to all the women for their contributions to this study.
Dermatomyofibroma: additional observations on a distinctive cutaneous myofibroblastic tumour with emphasis on differential diagnosis
Authors: T. MENTZEL, E. CALONJE, C.D.M. FLETCHER
Journal: British Journal of Dermatology (1993)

Summary Following the very recent description of a benign plaque-like myofibroblastic tumour of the skin, known as dermatomyofibroma, we present four further cases, emphasizing its clinical features and its histological differential diagnosis. Three patients were adult females and one was a boy. Two of the lesions arose on the anterior abdominal wall, one on the shoulder, and one on the neck. Clinically, there was often close resemblance to a keloid. Follow-up revealed no evidence of recurrence after simple excision. Histologically, these were non-encapsulated but well-circumscribed, plaque-like lesions located in the reticular dermis, and composed of fascicles of monomorphic myofibroblasts, orientated parallel to the skin surface. Immunohistochemically. most of the tumour cells expressed alpha-smooth-muscle actin. The principal differential diagnosis is plaque-stage dermatofibrosarcoma protuberans. Other differential diagnoses include diffuse neurofibroma, dermatofibroma and other myofibroblastic skin tumours.
Sudan floods bring threat of disease
Authors: P. Moszynski
Journal: BMJ (2003)

Record flooding in east Africa has made hundreds of thousands of people homeless in Sudan, with millions more at risk as the rising water of the Nile threatens to inundate Khartoum, spreading disease and overwhelming sanitation services.

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One of thousands of families made homeless by flooding in Kassala 

Credit: ABD RAUF/AP

Kassala, the largest town in eastern Sudan, has been declared a disaster zone, with 80% of the population homeless after the River Qash overflowed …

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The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib
Authors: C Albers, H Leischner, M Verbeek, C Yu, A L Illert, C Peschel, N von Bubnoff, J Duyster
Journal: Leukemia (2013)
FATALITY RESULTING FROM THE USE OF LASHLURE ON THE EYEBROW AND EYELASHES
Authors: S. B. Forbes
Journal: JAMA (1934)

During the past twelve months, instances of dermatoconjunctivitis due to the use of eyelash and eyebrow dyes have been reported by Greenbaum,1Harner,2Bourbon,3Jamieson,4McCally, Farmer and Loomis,5and Moran.6In the cases reported by the last two the reaction was severe enough to produce ulceration and necrosis of the cornea. Six of the reported cases were due to the use of the preparation LashLure, and two followed the use of Godefroy French Hair Coloring-Larieuse.  The case reported here followed immediately the use of Lash-Lure and terminated fatally.  REPORT OF CASE  A woman, aged 52, who had considered herself in good health, had her right eyebrow plucked and the dye Lash-Lure applied to the right brow and eyelashes. This was done by her daughter, an employee of a beauty parlor. The adjacent tissues began to burn and swell within thirty seconds after the
PERFORATION OF ILEUM BY WIRE SPIKE.
Authors: J. CLARK STEWART
Journal: JAMA (1907)

The following case, which is of unusual interest in some respects, came into my service at the City Hospital. This patient was operated on in June, 1906, by my colleague, Dr. A. E. Benjamin, who reported the case in the<i>Annals of Surgery</i>, February, 1907. At this time were removed from the stomach fifty-two nails and some glass pieces, the photo of which is here reproduced. His history, in brief, up to that time is as follows: <h3>Patient.</h3> —E. W., aged 47, has been a professional nail and glass eater for twenty years without suffering serious inconvenience until February, 1906. <h3>History.</h3> —Four years ago he had a moderately severe gastric hemorrhage, and for the past four months he has vomited considerable blackish fluid, and his stools have been black at times. He has lost 23 pounds and feels weak. Examination at this time showed marked dilatation of the stomach, the
Anxiety state after "Sex education"
Authors: B. H. Burne
Journal: BMJ (1967)

MEDICALIShURNALvolved the surrounding muscles, causing con- siderable damage.In each case an unfortunate milkman had slipped on a wet and slippery pavement or step and fallen heavily on a glass bottle, which had shattered and caused the injury.Altogether a total of about three hours was taken for treatment of these cases, the work involving up to three doctors at any one time, with a difficult exploration and nerve suture.Our casualty department sees and treats between 80 and 120 new attendances daily from a large catchment area, including dock- yards and a motorway.There is one duty casualty officer, with orthopaedic and surgical firms on call, and a second casualty officer seeing reattendances for a few hours in the morning only, and such lacerations impose a severe strain, involving delay in treatment for many patients.Prevention is always better than a cure, which often is incomplete in these cases.Little can be done about our English weather and wet slippery pavements, but surely in this age of plastics much time and expense would be saved to busy casualty departments and the public if milk, distributors and brewers would supply their products in polyethylene bottles.Is there some objection to this or do these firms not realize the potential danger of their containers ?-I am, etc.,
Letter: safer cigarettes.
Authors: G Godber
Journal: BMJ (1975)

Risks of Total Hip Replacement SM,-In your leading aricle (10 May, p. 296) on the risks of total hip rePlacement, you mention introperative circulatory collapse attributed to acrylic cement.Modig says that the literature records "at least 30 deaths during the operative procedure and possibly there are many moire unrecorded cases."The original reports which led to the Department of Health and Social Security -setting up an inquiry in 1971 a-re now over four years old and during these four years the use of acrylic cement in hip therapy must have mutliplied many times, but we no
Clinical Impact of Conventional Endosonography and Endoscopic Ultrasound-guided Fine-needle Aspiration in the Assessment of Patients with Barrett’s Esophagus and High-grade Dysplasia or Intramucosal Carcinoma who have been Referred for Endoscopic Ablation Therapy
Authors: V. M. Shami, A. Villaverde, L. Stearns, K. D. Chi, T. P. Kinney, G. B. Rogers, C. E. Dye, I. Waxman
Journal: Endoscopy (2006)

Background and Study Aims: Endoscopic mucosal resection and photodynamic therapy are exciting, minimally invasive curative techniques that represent an alternative to surgery in patients with Barrett's esophagus and high-grade dysplasia or intramucosal adenocarcinoma. However, there is lack of uniformity regarding which staging method should be used prior to therapy, and some investigators even question whether staging is required prior to ablation. We report our experience with a protocol of conventional endoscopic ultrasound staging prior to endoscopic therapy. Patients and Methods: A total of 25 consecutive patients with a diagnosis of high-grade dysplasia or intramucosal adenocarcinoma in Barrett's esophagus who had been referred to the University of Chicago for staging in preparation for endoscopic therapy between March 2002 and November 2004 were included in the study. All 25 patients underwent repeat diagnostic endoscopy and conventional endosonography with a radial echo endoscope. Any suspicious lymph nodes that were detected were sampled using endoscopic ultrasound-guided fine-needle aspiration. Results: Baseline pathology in the 25 patients (mean age 70, range 49 - 85) revealed high-grade dysplasia in 12 patients and intramucosal carcinoma in 13 patients. Five patients were found to have submucosal invasion on conventional endosonography. Seven patients had suspicious adenopathy, six regional (N1) and one metastatic to the celiac axis (M1a). Fine-needle aspiration confirmed malignancy in five of these seven patients. Based on these results, five patients (20 %) were deemed to be unsuitable candidates for endoscopic therapy. Conclusions: By detecting unsuspected malignant lymphadenopathy, conventional endosonography and endoscopic ultrasound with fine-needle aspiration dramatically changed the course of management in 20 % of patients referred for endoscopic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma. Based on our results, we believe that conventional endosonography and endoscopic ultrasound with fine-needle aspiration when nodal disease is present should be performed routinely in all patients referred for endoscopic therapy in this setting.
In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time
Authors: M. Goetz, R. Kiesslich, H.-P. Dienes, U. Drebber, E. Murr, A. Hoffman, S. Kanzler, P. Galle, P. Delaney, M. Neurath
Journal: Endoscopy (2008)

Confocal endomicroscopy is a unique novel tool for in vivo histology in humans. Due to limitations imposed by the form of the equipment and by sterilization workflows, its use has been limited to the gastrointestinal tract so far. We have developed a rigid miniaturized probe for confocal endomicroscopy of the human liver during laparoscopy.To assess the feasibility and potential clinical value of this new system (diameter 6.3 mm), 25 patients with liver disease were examined during routine minilaparoscopy under conscious sedation.Subsurface serial images (from surface to 250 microm) were generated in real time after fluorescein injection, permitting visualization of hepatocytes, bile ducts, sinusoids, and collagen fibers in vivo. Typical appearances of liver diseases were identified. Confocal diagnosis of moderate-to-severe steatosis and pericellular fibrosis correlated well with histopathologic analysis of subsequent biopsies (83.3 % and 84.6 %, respectively). In addition, intra-abdominal structures such as gallbladder, omentum, and stomach were analyzed by endomicroscopy.A miniaturized imaging system for confocal laparoscopy allowed in vivo microscopic analysis of healthy and diseased human liver for the first time during ongoing minilaparoscopy. Although such in vivo imaging does not yet compete with conventional histopathology, this novel confocal laparoscopy system may be of future relevance for immediate morphodynamic analysis in liver disease and the targeting of biopsies in vivo.
Abstract 4899: Development of a quantitative measurement of p53 – p53 antibody interactions
Authors: Donald H. Atha, Vytas Reipa
Journal: Cancer Research (2011)

Abstract We are developing methods to quantify antibody interactions that includes a quartz crystal microbalance (QCM) system to measure, on a molecular basis, the interaction of p53 and anti-p53 antibodies. Previously, as a model system, we developed a reference device consisting of p53 protein (human wild type), characterized by mass spectroscopy and immobilized at various concentrations on a glass slide. The device is designed as a reference control to be used with immunohistochemical (IHC) assays that incorporate commercially available anti-p53 antibodies and probes. In the current study, we compared three different monoclonal antibodies (clones: BP53.12, PAb 1801 and DO-1) for their ability to detect p53 in HT1080 cells. Both visible microscopy (diaminobenzidine probe) and flow cytometry (AlexaFluor 488 probe) showed significant increases in staining intensity compared to controls without primary antibody. However, quantification of these observations requires direct measurement of the concentration of the p53 and the concentrations and specificities of the antibodies. For this the p53 protein is covalently immobilized on glass coated quartz crystals and the resonance frequency shift is followed in-situ. The functionalized sensor is then incubated with the anti-p53 antibody, which provides a direct gravimetric measure of antibody-antigen binding. This allows the comparison of the surface immobilized protein concentrations with those previously obtained by fluorescence measurement. The p53 functionalized QCM system offers an independent measure of surface immobilized protein concentration and is essential in the development of our IHC calibration prototypes. These results also provide a benchmark for comparing systems that may be used in developing molecular diagnostic assays such as aspiration biopsy analysis and the detection of biomarker proteins in blood and urine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4899. doi:10.1158/1538-7445.AM2011-4899
Efficacy of vitamin A in reducing preschool child mortality in Nepal
Authors: K.P. West, J. Katz, S.C. LeClerq, E.K. Pradhan, J.M. Tielsch, A. Sommer, R.P. Pokhrel, S.K. Khatry, S.R. Shrestha, M.R. Pandey
Journal: The Lancet (1991)

Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results. To resolve the question, a randomised, double-masked, placebo-controlled community trial of 28,630 children aged 6-72 months was carried out in rural Nepal, an area representative of the Gangetic flood plain of South Asia. Randomisation was carried out by administrative ward; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents. After 12 months, the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 (95% confidence interval 0.56-0.88), equivalent to a 30% reduction in mortality. The trial, which had been planned to last 2 years, was discontinued. The reduction in mortality was present in both sexes (relative risk for boys 0.77; for girls 0.65), at all ages (range of relative risks 0.83-0.50), and throughout the year (0.76-0.67). The reduction in mortality risk was not affected by acute nutritional status, as measured by arm circumference. Thus, periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries.
Gas Gangrene After Intramuscular Injection of Epinephrine: Report of Fatal Case
Authors: Robert Van Hook, Alexander G. Vandevelde
Journal: Annals of Internal Medicine (1975)

Letters1 November 1975Gas Gangrene After Intramuscular Injection of Epinephrine: Report of Fatal CaseROBERT VAN HOOK, M.D., ALEXANDER G. VANDEVELDE, M.D.ROBERT VAN HOOK, M.D.Search for more papers by this author, ALEXANDER G. VANDEVELDE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-5-669 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGas gangrene developing at the site of intramuscular injection is fulminating and associated with high mortality. We report here a patient who died 36 hours after injection of epinephrine in oil in the buttocks. Clostridial myonecrosis has occurred under similar circumstances since administration of drugs intramuscularly became common practice at the beginning of this century. Touraine (1), reviewing the subject in 1936, mentioned epinephrine as the most frequently offending drug. After World War II additional patients were described by Marshall and Sims (2) and Koons and Boyden (3), who referred to another 30 cases in Brazil.Our patient, a 64-year-old...References1. TOURAINE A: La gangrène gazeuse après injections medicamenteuses. Presse Med 44:674-677, 1936 Google Scholar2. MARSHALL V and SIMS P: Gas gangrene after injection of adrenaline-in-oil with report of three cases. Med J Aust 2:653-656, 1960 CrossrefGoogle Scholar3. KOONS T and BOYDEN G: Gas gangrene from parenteral injection. JAMA 175:46-47, 1961 CrossrefMedlineGoogle Scholar4. BISHOP R and MARSHALL V: Enhancement of Clostridium welchii infection by adrenaline-in-oil. Med J Aust 2:656-657, 1960 CrossrefGoogle Scholar5. DREWETT S, PAYNE D, and TUKE W: Skin distribution of Clostridium welchii: use of iodophor as sporicidal agent. Lancet 1:1172-1173,1972 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT VAN HOOK, M.D.; ALEXANDER G. VANDEVELDE, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEpinephrine auto-injector needle lengthsEpinephrine auto-injector needle length: what is the ideal length?Parenteral drug administrationConditions of the Skin/Soft Tissue in the ERGas Gangrene following Intramuscular Injection of Vitamin B-Complex: Report of a Fatal CaseLes infections anaérobies des tissus mousClostridial myonecrosis resulting from subcutaneous epinephrine suspension injectionIntramuscular Injection Abscess — Past Lessons RelearnedClostridial myonecrosisNecrotizing Soft Tissue Infections 1 November 1975Volume 83, Issue 5Page: 669-670KeywordsDrug administrationDrugsEpinephrineIntramuscular injectionsMortalityOils ePublished: 1 December 2008 Issue Published: 1 November 1975 PDF downloadLoading ...
Increased Tissue Factor Pathway Inhibitor Activity in IDDM Patients With Nephropathy
Authors: Hiroki Yokoyama, Bjarne Myrup, Peter Rossing, Per B østergaard
Journal: Diabetes Care (1996)

Tissue factor pathway inhibitor (TFPI) is bound to vascular endothelium (presumably to heparan sulfate) and circulates in complex with plasma lipoproteins. It directly binds and inhibits factor Xa. The purpose of the study is to investigate whether plasma TFPI activity is altered in IDDM and nephropathy and to evaluate the possible determinants of the alteration.We assessed plasma concentration of TFPI (total, truncated, and domain 3 TFPI) and plasma activity of factor Xa inhibition in nondiabetic control subjects (n = 22) and in IDDM patients with normoalbuminuria (urinary albumin excretion rate [UAE] < 30 mg/24h, n = 17), incipient nephropathy (UAE 30-300 mg/24 h, n = 17), clinical nephropathy (UAE > 300 mg/24h, n = 25).Total, truncated, and domain 3 TFPI concentrations were increased in IDDm patients compared with those in control subjects and were more pronounced in IDDM patients with nephropathy. Plasma activity of factor Xa inhibition measured by HEPTEST (Haemachem, St. Louis, MO) assay was increased in IDDM patients, especially in those with nephropathy. TFPI-dependent factor Xa inhibition, obtained as the difference in clotting time with and without adding activity-neutralizing anti-TFPI antibody to samples, was increased in IDDm patients with nephropathy. This was, however, not sufficient to inhibit the biological activity of factor Xa as demonstrated by increased levels of prothrombin fragment 1 + 2. LDL cholesterol and HbA1c were independently correlated to plasma TFPI.Inhibition of factor Xa activity is increased in IDDM patients with nephropathy, mainly because of increased plasma TFPI activity. The increased plasma TFPI activity in these patients may be associated with and regulated by LDL in plasma and metabolic control. The anticoagulant activity of TFPI may attenuate the hypercoagulable state in diabetes but does not seem to be able to normalize hemostasis.