tbuckley/cabot-search huggingface dataset:
Abstract 2669: Early-phase trials in patients with advanced gallbladder cancer and cholangiocarcinoma: The MD Anderson Clinical Center for Targeted Therapy experience
Authors: Ishwaria M. Subbiah, Apostolia M. Tsimberidou, Aung Naing, Vivek Subbiah, Ahmed O. Kaseb, Gerald S. Falchook, Siqing Fu, David S. Hong, Sarina A. Piha-Paul, Jennifer J. Wheler, Filip Janku, Razelle Kurzrock
Journal: Cancer Research (2012)

Abstract BACKGROUND: Patients with cholangiocarcinoma (CC) and gallbladder carcinoma (GC) have few effective therapeutic options in the relapsed and/or metastatic setting. With that purpose, we analyzed the characteristics and outcomes of patients with advanced CC and GC treated on early-phase clinical trials in the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. METHODS: We searched an electronic database of consecutive pts with GC and CC referred to the Clinical Center for Targeted Therapy starting in November 2004. We assessed the relationship between types of clinical trial and pts’ tumor types, progression-free survival, and mutations. RESULTS: Of the 72 patients with CC and GC referred to the clinic, 32 (44%) were not enrolled in a clinical trials mainly due to deterioration of performance status (n=25), decision to pursue alternate therapies (n=6), and insurance denial (n=1). Forty pts (5 w GC; 35 w CC) who received treatment on early clinical trials are included in this analysis. The median age was 60.2 yrs (range, 41.4-73.6 yrs). ECOG performance status (PS) was 0-1 in 36 pts (90%) and 2 in 4 (10%). Median number of prior therapies was 3 (range 0-17). Six pts were not restaged due to early disease progression. Of the 40 pts evaluable for response, 8 (20%) had stable disease (SD) &amp;gt; 6 months and 3 (8%) had a partial response (PR) (total SD &amp;gt; 6 mos/PR = 28%). Highest rates of SD &amp;gt; 6 mos/PR were observed in patients treated with protocols that included hepatic arterial infusion drug administration (7/17 = 41%) or anti-angiogenic agents (9/24 = 38%) (with 6 of these pts receiving treatment that included hepatic arterial infusion chemotherapy combined with a systemic anti-angiogenic agent). SD lasting 9 months was also seen in 1 pt treated with a MEK inhibitor. Median progression-free survival for the 40 pts was 2.0 months 9 (95% CI 1.7, 2.8) on early-phase clinical trials versus 3.0 months on their last FDA-approved treatment before Phase I referral (95% CI 2.3, 3.7). CONCLUSIONS: About one-third of patients with CC and GC referred for early-phase trials cannot be enrolled because of poor performance status. Twenty-eight percent of patients who met eligibility criteria achieved SD &amp;gt; 6 mos/PR, with responses predominantly observed in regimens that contained locoregional treatment, anti-angiogenic agents, or a targeted MEK inhibitor. 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 2669. doi:1538-7445.AM2012-2669
Parkinson's disease in China: prevalence in Beijing, Xian, and Shanghai
Authors: Zhen-Xin Zhang, Gustavo C Roman, Zhen Hong, Cheng-Bing Wu, Qiu-Ming Qu, Jue-Bing Huang, Bing Zhou, Zhi-Ping Geng, Ji-Xing Wu, Hong-Bo Wen, Heng Zhao, Gwendolyn EP Zahner
Journal: The Lancet (2005)
Do Bacteria Cause Chronic Polyarthritis?
Authors: John A. Mills
Journal: New England Journal of Medicine (1989)

IS infection involved in the pathogenesis of chronic polyarthritis? Many teeth have been extracted, high colonic irrigations given, and prolonged courses of antibiotics administered in the belief that it is. The best supporting evidence in humans is the clear association of infection in the genital tract or bowel with Reiter's syndrome. The fact that various organisms from two different sites of infection can induce this syndrome also suggests an important role for the host's response, an argument strengthened by the predisposing influence of the HLA-B27 phenotype. In other arthritides, including rheumatoid arthritis, many highly sophisticated attempts to isolate live organisms . . .
The Truth in the Light
Authors: N. Eastman
Journal: BMJ (1995)

The views of 89 vocational trainees were compared with those of 45 doctors concerned in schemes of vocational training for general practice. Both groups agreed over most points, except on the desirability of compulsory vocational training: 42 of the trainees thought this to be desirable compared with 35 of the teachers. The composite scheme favoured by both trainees and teachers offered an initial period in general practice together with an organized course of seminars throughout the training period. The subjects in which most considered hospital experience essential were paediatrics, general medicine, and obstetrics and gynaecology.
Fairfield County (Conn.) Medical Society.
Authors: L. T. Day
Journal: JAMA (1895)

Westport,Conn., April 10,1895. <h3>To the Editor:</h3> —At the one hundred and third annual meeting of the Fairfield County Medical Association, held in Bridgeport, April 9, the following officers were elected: F. B. Baker, East Norwalk, President; J. W. Wright, Bridgeport, Vice-President; L. T. Day, Westport, Clerk; C. R. Hexamer, Stamford, Corresponding Reporter. Censors: F. M. Wilson, Bridgeport; M.V.B. Dunham, Greenfield Hill; W. S. Watson, Danbury. Very truly yours,
P202 Clinics for obstructive sleep apnoea hypopnoea (OSAH)--time for a change?
Authors: T. S. Jordan, E. Idris, R. Haqqee, M. Allen
Journal: Thorax (2010)

<h3>Introduction</h3> OSAH is a significant public health problem. Growing awareness and rising prevalence is increasing demand for sleep services. Many Trusts are unable to expand existing clinic space to meet this demand. In its recent White Paper<sup>1</sup>, the Government laid out its vision of a patient-centred NHS, pledging patients more choice and control over decision making about their care. However, a sizeable proportion of patients with suspected OSAH are from the working population, yet the NHS does not routinely provide clinics outside normal working hours. <h3>Method</h3> Patients referred for suspected OSAH were randomly appointed to either daytime or evening clinics. Over a 3-month period, opinions of this out-of-hours service and problems encountered on attending the clinics were surveyed by questionnaire completed by patients in the waiting room. <h3>Results</h3> Of 165 patients appointed, 156 attended and 136 (87%) completed questionnaires (mean age 50.4 years (range 18–75), 74% male). Over half (57% [77/136]) were in employment of which 21% (16/77) worked shifts and 79% (61/77) days. The rest (59/136 (43%)) were non-working due to disability (42% (24/59)), retirement (39% [23/59]), were full-time carers (10% [6/59]) or were unemployed (8% [5/59]). Patient responses are detailed in Abstract P202 Table 1. In addition, 41% (13/32) of workers seen in evening clinics felt that work would have been a problem if attending in the day. DNA rates were higher for daytime clinics (7%) than evenings (3%). The proportion of workers in the DNAs was unknown. <h3>Conclusions</h3> There is a considerable demand for out-of-hours sleep clinics. This is predominantly from those in employment. Making up a large proportion of patients referred for suspected OSAH, over half of these patients preferred evening clinics. Provision of this clearly demanded service requires a change in current working practice. Not only would out-of-hours clinics be a move towards delivering the patient-centred NHS pledged in the recent Government White Paper<sup>1</sup>, but would deliver the increased clinic capacity required to meet rising demand.
Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data
Authors: Lori Newman, Mary Kamb, Sarah Hawkes, Gabriela Gomez, Lale Say, Armando Seuc, Nathalie Broutet
Journal: PLoS Medicine (2013)

The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis.Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage.Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary.
Evaluation of the Antiangiogenic Potential of AQ4N
Authors: Martin O'Rourke, Claire Ward, Jenny Worthington, Julie McKenna, Andrea Valentine, Tracy Robson, David G. Hirst, Stephanie R. McKeown
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A number of cytotoxic chemotherapy agents tested at low concentrations show antiangiogenic properties with limited cytotoxicity, e.g., cyclophosphamide, tirapazamine, and mitoxantrone. AQ4N is a bioreductive alkylaminoanthraquinone that is cytotoxic when reduced to AQ4; hence, it can be used to target hypoxic tumor cells. AQ4N is structurally similar to mitoxantrone and was evaluated for antiangiogenic properties without the need for bioreduction. Experimental Design: The effect of AQ4N and fumagillin on human microvascular endothelial cells (HMEC-1) was measured using a variety of in vitro assays, i.e., 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound scrape, tubule formation, rat aortic ring, and invasion assays. Low-dose AQ4N (20 mg/kg) was also given in vivo to mice bearing a tumor in a dorsal skin flap. Results: AQ4N (10−11 to 10−5 mol/L) had no effect on HMEC-1 viability. AQ4N (10−9 to 10−5mol/L) caused a sigmoidal dose-dependent inhibition of endothelial cell migration in the wound scrape model. Fumagillin showed a similar response over a lower dose range (10−13 to 10−9 mol/L); however, the maximal inhibition was less (25% versus 43% for AQ4N). AQ4N inhibited HMEC-1 cell contacts on Matrigel (10−8 to 10−5 mol/L), HMEC-1 cell invasion, and sprouting in rat aorta explants. Immunofluorescence staining with tubulin, vimentim, dynein, and phalloidin revealed that AQ4N caused disruption to the cell cytoskeleton. When AQ4N (20 mg/kg) was given in vivo for 5 days, microvessels disappeared in LNCaP tumors grown in a dorsal skin flap. Conclusions: This combination of assays has shown that AQ4N possesses antiangiogenic effects in normoxic conditions, which could potentially contribute to antitumor activity.
Ibrutinib for the Treatment of Mantle Cell Lymphoma
Authors: Alex F. Herrera, Eric D. Jacobsen
Journal: Clinical Cancer Research (2014)

Abstract Ibrutinib (PCI-32765)—a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway—was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The drug was granted accelerated approval based on the findings of an international, multicenter, single-arm phase II study that enrolled patients with relapsed or refractory MCL. In the study, ibrutinib (560 mg daily) was well tolerated as a single agent and resulted in an overall response rate of 68% and an estimated median response duration of 17.5 months. Ibrutinib's response rate and duration of response compare favorably with those for other novel agents approved for the treatment of relapsed or refractory MCL, while being less toxic than most chemotherapy or chemoimmunotherapy regimens. Ibrutinib is currently being studied in combination with chemoimmunotherapy, monoclonal antibody therapy, and novel agents in both the initial and the relapsed/refractory treatment settings. We review the mechanism of action, preclinical and clinical development, and the role of ibrutinib in the context of other available treatments. Clin Cancer Res; 20(21); 5365–71. ©2014 AACR.
Treatment of acute myelocytic leukemia: a study by cancer and leukemia group B
Authors: KR Rai, JF Holland, OJ Glidewell, V Weinberg, K Brunner, JP Obrecht, HD Preisler, IW Nawabi, D Prager, RW Carey, MR Cooper, F Haurani, JL Hutchison, RT Silver, G Falkson, P Wiernik, HC Hoagland, CD Bloomfield, GW James, A Gottlieb, SV Ramanan, J Blom, NI Nissen, A Bank, RR Ellison, F Kung, P Henry, OR McIntyre, SK Kaan
Journal: Blood (1981)
Expression of naked DNA in human, pig, and mouse skin.
Authors: U R Hengge, P S Walker, J C Vogel
Journal: Journal of Clinical Investigation (1996)

The insertion and expression of genes in the epidermis may have a variety of therapeutic uses, including the treatment of skin diseases. Here we show that when both human skin organ cultures and human skin grafts on immunocompromised mice are injected with naked DNA, the DNA is taken-up and genes are expressed in the epidermis in a manner similar to both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in the epidermis, but also in the dermis and underlying fat and muscle tissue, and is expressed at lower levels. These findings suggest that genes can be expressed in human skin, after injection of naked DNA, and indicate that pig skin is an appropriate model for the study of DNA uptake and gene expression in human skin. The organ cultures of human and pig skin may be useful in understanding how naked DNA is internalized and expressed after in vivo injections. Additionally, skin obtained from patients with skin disease may be studied as skin grafts and organ cultures to help optimize genetic approaches for the treatment of skin diseases prior to clinical trials, by determining if the injected gene can provide a therapeutic benefit.
Effect of I-Norepinephrine on the Diameter of Pial Arterioles and Arteries in the Cat
Authors: M. Wahl, W. Kuschinsky, O. Bosse, J. Olesen, N. A. Lassen, D. H. Ingvar, J. Michaelis, K. Thurau
Journal: Circulation Research (1972)

The influence of norepinephrine on the diameter of single pial arteries and arterioles was investigated by adding the drug to the perivascular space with micropipettes. The mock spinal fluid solution in which the norepinephrine was dissolved contained 0, 11, or 22 mEq/liter of bicarbonate. These concentrations of bicarbonate were by themselves found to dilate, cause no change, and constrict the pial vessels, respectively. Concentration-response curves with 11 mEq/liter of bicarbonate over the concentration range of 5 x 10 -4 to 5 mmoles/liter of norepinephrine showed significant constriction at 5 x 10 -2 mmoles/liter and maximal constriction (40% of diameter) at 2.5 mmoles/liter. In bicarbonate-free solution, the slope of the concentration-response curves was less, and at 22 mEq/liter of bicarbonate norepinephrine had no effect. The pial arteries seemed to be less sensitive than the mesenteric and the cremasteric arteries to norepinephrine. The present data demonstrate the existence of norepinephrine receptors on the pial arterial smooth muscle cells, which satisfies the major requirement for the possible existence of a sympathetic control of cerebral blood flow.
Vulval and vaginal adenosis
Authors: None Kranl, None Zelger, None Kofler, None Heim, None Sepp, None Fritsch
Journal: British Journal of Dermatology (1998)

Vaginal adenosis is defined by the presence of metaplastic cervical or endometrial epithelium within the vaginal wall, thought to be derived from persistent Müllerian (synonymous with paramesonephric) epithelium islets in postembryonic life. Spontaneous vaginal adenosis appears to be a fairly common (present in about 10% of adult women) but mostly insignificant coincidental finding. In women prenatally exposed to diethylstilboestrol (DES), vaginal adenosis may arise in up to 90% and is associated with a high risk of vaginal carcinoma. Since the withdrawal of DES from the market, vaginal adenosis has virtually disappeared from the medical literature. A case of vaginal adenosis is presented in a middle-aged woman who had not been prenatally exposed to DES. The lesions differed from the spontaneous type by their sudden appearance, their extent and their pronounced subjective symptoms. It is speculated that protracted oral contraceptive intake may have played a causative role.
Determination of heparin-induced thrombocytopenia: A rapid flow cytometric assay for direct demonstration of antibody-mediated platelet activation
Authors: Aaron Tomer, Cynthia Masalunga, Thomas C. Abshire
Journal: American Journal of Hematology (1999)

Heparin-induced thrombocytopenia (HIT) and thrombosis are serious complications of heparin therapy. Recently, we have reported a practical and rapid functional flow cytometric assay (FCA) for the diagnosis of HIT with high specificity and sensitivity compared with the radioactive serotonin-release assay (SRA). In the present study, we added an immune-neutralization assay to directly demonstrate the antibody-mediated process, and tested the immune compatibility of low-molecular-weight heparin (LMWH) Lovenox and the heparinoid Orgaran (danaproid) using plasma from 18 patients with HIT confirmed by both FCA and SRA. The clinical utility of this modified method is demonstrated by a pediatric patient with a complex clinical presentation who developed thrombocytopenia with multiple thromboses while on heparin therapy. ELISA and SRA (performed in three independent laboratories) for diagnosis of HIT were both negative. In contrast, the FCA for detecting activated platelets expressing anionic phospholipids, was highly and reproducibly positive with both unfractionated and LMWH. Another FCA also demonstrated the surface expression of the α-granule membrane p-selectin (CD62p). Compatibility testing with the heparinoid Orgaran was also positive (and with plasma from 4 of the 18 patients with HIT). Heparin was discontinued, along with full recovery of the platelet count. The capacity of the patient's plasma to activate platelets in the presence of heparin gradually decreased over 4 weeks consistent with antibody clearance. The responsible mechanism was clarified using an immune-neutralization assay, which showed a dose response neutralization of the plasma activity by antibodies against human Immunoglobulin G (IgG) and IgM. This assay was also reproducible in the 18 patients with HIT. We conclude that the functional FCA with its modification is practical, sensitive, and specific for reliable diagnosis of HIT. It can simultaneously assess the compatibility of alternative therapies and directly confirm the antibody-mediated process. Further, it is particularly useful to clarify mechanisms of thrombocytopenia and thrombosis and to direct therapy in patients with a complex presentation and confounding laboratory results who often need prompt diagnosis and treatment. Am. J. Hematol. 61:53–61, 1999. © 1999 Wiley-Liss, Inc.
Weapon Involvement and Injury Outcomes in Family and Intimate Assaults
Authors: Linda E. Saltzman
Journal: JAMA (1992)

To compare the risk of death and the risk of nonfatal injury during firearm-associated family and intimate assaults (FIAs) with the risks during non-firearm-associated FIAs.Records review of police incident reports of FIAs that occurred in 1984. Victim outcomes (death, nonfatal injury, no injury) and weapon involvement were examined for incidents involving only one perpetrator.City of Atlanta, Ga, within Fulton County.Stratified sample (n = 142) of victims of nonfatal FIAs, drawn from seven nonfatal crime categories, plus all fatal victims (n = 23) of FIAs.Risk of death (vs nonfatal injury or no injury) during FIAs involving firearms, relative to other types of weapons; risk of nonfatal injury (vs all other outcomes, including death) during FIAs involving firearms, relative to other types of weapons.Firearm-associated FIAs were 3.0 times (95% confidence interval, 0.9 to 10.0) more likely to result in death than FIAs involving knives or other cutting instruments and 23.4 times (95% confidence interval, 7.0 to 78.6) more likely to result in death than FIAs involving other weapons or bodily force. Overall, firearm-associated FIAs were 12.0 times (95% confidence interval, 4.6 to 31.5) more likely to result in death than non-firearm-associated FIAs.Strategies for limiting the number of deaths and injuries resulting from FIAs include reducing the access of potential FIA assailants to firearms, modifying firearm lethality through redesign, and establishing programs for primary prevention of violence among intimates.
Revolution in health care
Authors: Neil Bennet
Journal: The Lancet (2011)

Giving a speech in 1960, the year after the Cuban Revolution, Che Guevara spoke of the role of medicine in the new Cuba, telling supporters "our task now is to orient the creative abilities of all medical professionals toward the tasks of social medicine". In Revolutionary Doctors, Steve Brouwer assesses the accomplishments of those who were to follow Che's prescription, tracing the development of Cuba's systems of health care and medical education since the revolution, together with the role of medicine in the country's relations with the outside world.