tbuckley/cabot-search huggingface dataset:
Radiation Therapy in Cancer Management
Authors: Luther W. Bredy
Journal: JAMA (1972)

Although radiation therapy has been used for more than half a century in the management of cancer, it did not assume a prominent role in the United States until the late 1950s when supervoltage radiation therapy became available in many centers. With the successes achieved in those centers, there developed an increased interest leading to a better understanding of the biological and physical bases of radiation oncology. Wider applications and rapid improvement in results came about through more precise and scientific use of radiation techniques. The radiation oncologist, therefore, is involved in the care of a majority of patients with cancer. Medical students and many physicians, however, have had little, if any, useful introduction to the utilization of radiation techniques in treating patients with cancer. The authors point out that recent improvements in medical school curricula have provided the students a somewhat cursory introduction to the subject. The major purpose
Genome instability of ageing stem cells—Induction and defence mechanisms
Authors: Martin D. Burkhalter, K. Lenhard Rudolph, Tobias Sperka
Journal: Ageing Research Reviews (2015)

The mammalian organism is comprised of tissue types with varying degrees of self-renewal and regenerative capacity. In most organs self-renewing tissue-specific stem and progenitor cells contribute to organ maintenance, and it is vital to maintain a functional stem cell pool to preserve organ homeostasis. Various conditions like tissue injury, stress responses, and regeneration challenge the stem cell pool to re-establish homeostasis (Fig. 1). However, with increasing age the functionality of adult stem cells declines and genomic mutations accumulate. These defects affect different cellular response pathways and lead to impairments in regeneration, stress tolerance, and organ function as well as to an increased risk for the development of ageing associated diseases and cancer. Maintenance of the genome appears to be of utmost importance to preserve stem cell function and to reduce the risk of ageing associated dysfunctions and pathologies. In this review, we discuss the causal link between stem cell dysfunction and DNA damage accrual, different strategies how stem cells maintain genome integrity, and how these processes are affected during ageing.
NHS ahead of schedule on efficiency savings, says health secretary
Authors: J. Wise
Journal: BMJ (2011)

Health secretary Andrew Lansley painted a rosy picture of the state of the NHS finances when questioned by MPs this week.

Appearing before the Commons health select committee Mr Lansley said: “Significant progress has already been made. The QIPP (Quality, Innovation, Productivity and Prevention) programme is already delivering savings.”

He said that the Audit Commission had reported efficiency savings over the service as a whole of £4.3bn (€4.9bn; $6.8bn) during 2010-11. And primary care trusts had reported planned efficiency savings of £5.9bn in 2011-12. “If those savings are fully achieved that would put us ahead of …
The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity
Authors: Francesca Finetti, Michela Pellegrini, Cristina Ulivieri, Maria Teresa Savino, Eugenio Paccagnini, Chiara Ginanneschi, Luisa Lanfrancone, Pier Giuseppe Pelicci, Cosima T. Baldari
Journal: Blood (2008)
AMA issues guidelines on end of life care
Authors: F. Charatan
Journal: BMJ (1999)

A penalized expectation of determinant (ED)-optimal design with a discrete parameter distribution was used to find an optimal experimental design for assessment of enzyme kinetics in a screening environment. A data set for enzyme kinetic data (<i>V</i><sub>max</sub> and <i>K</i><sub>m</sub>) was collected from previously reported studies, and every <i>V</i><sub>max</sub>/<i>K</i><sub>m</sub> pair (<i>n</i> = 76) was taken to represent a unique drug compound. The design was restricted to 15 samples, an incubation time of up to 40 min, and starting concentrations (<i>C</i><sub>0</sub>) for the incubation between 0.01 and 100 μM. The optimization was performed by finding the sample times and <i>C</i><sub>0</sub> returning the lowest uncertainty (S.E.) of the model parameter estimates. Individual optimal designs, one general optimal design and one, for laboratory practice suitable, pragmatic optimal design (OD) were obtained. In addition, a standard design (STD-D), representing a commonly applied approach for metabolic stability investigations, was constructed. Simulations were performed for OD and STD-D by using the Michaelis-Menten (MM) equation, and enzyme kinetic parameters were estimated with both MM and a monoexponential decay. OD generated a better result (relative standard error) for 99% of the compounds and an equal or better result [(root mean square error (RMSE)] for 78% of the compounds in estimation of metabolic intrinsic clearance. Furthermore, high-quality estimates (RMSE &lt; 30%) of both <i>V</i><sub>max</sub> and <i>K</i><sub>m</sub> could be obtained for a considerable number (26%) of the investigated compounds by using the suggested OD. The results presented in this study demonstrate that the output could generally be improved compared with that obtained from the standard approaches used today.
Clinical Approach to Endocrine Problems in Children
Authors: Alfred M. Bongiovanni
Journal: JAMA (1971)

This exposition provides exactly what the title implies. It is a sound, pedagogical clinical approach written for pediatricians. There are three major subdivisions—problems of weight, of height, and of sex. Chapters are introduced by schematic diagrams which depict the particular endocrine glands or nonendocrine factors, sometimes followed by a detailed tabulation of the several disorders considered within the main topic. The author properly emphasizes that many supposed endocrinological diseases are either variants of normal development or attributable to disorders of other systems. There is a profusion of good illustrations and case reports. Consistent with the avowed purpose of the text is the paucity of discussion of basic mechanisms. However, the application and explanation of appropriate laboratory tests is adequately included. It is difficult for a lone author to write a complete text without a reviewer finding some faults. For example, the repeated tabulation of urinary 17-ketosteroids in male precocious puberty
Electrolyte and Fluid Disturbances in Congestive Heart Failure
Authors: Charles K. Friedberg
Journal: New England Journal of Medicine (1951)

HEART failure primarily denotes failure of the heart as a pump — a deficiency in its ability to maintain an adequate blood flow to the tissues according to their needs under a physiologic range of requirements. Concomitantly, there is impairment of the capacity of one or more of the cardiac chambers to accept and expel the venous return. In consequence there are disturbances in flow and pressure and secondary physical and metabolic disturbances in various tissues.From the point of view of the clinician, heart failure is defined differently — as a syndrome characterized by breathlessness, orthopnea, nocturnal dyspnea, cardiac . . .
Basic Control of Reperfusion Effectively Protects Against Reperfusion Injury in a Realistic Rodent Model of Acute Limb Ischemia
Authors: Florian Dick, Jianhui Li, Marie-Noëlle Giraud, Christoph Kalka, Juerg Schmidli, Hendrik Tevaearai
Journal: Circulation (2008)

Background— Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model. Methods and Results— Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159±44% of normal ( P =0.016), whereas muscle viability and contraction force were reduced to 65±13% ( P =0.016) and 45±34% ( P =0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132±16% versus 185±42%; P =0.011) and muscle viability (74±11% versus 57±9%; P =0.004) and contraction force (68±40% versus 26±7%; P =0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion ( P =0.027). Conclusions— Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.
Reply to V. Fusco et al
Authors: Alison T. Stopeck, Allan Lipton, Jean-Jacques Body, Guenther G. Steger, Katia Tonkin, Richard H. de Boer, Mikhail Lichinitser, Yasuhiro Fujiwara, Denise A. Yardley, María Viniegra, Michelle Fan, Qi Jiang, Roger Dansey, Susie Jun, Ada Braun
Journal: Journal of Clinical Oncology (2011)
EARLY INVASIVE VS. CONSERVATIVE TREATMENT IN NON-ST-SEGMENT MYOCARDIAL INFARCTION: EVIDENCE FOR A RISK TREATMENT PARADOX?
Authors: Kim Smolderen, Paul S. Chan, Kensey Riley, Phil G. Jones, Donna M. Buchanan, Johan Denollet, Saket Girotra, Harlan M. Krumholz, John A. Spertus
Journal: Journal of the American College of Cardiology (2010)
Radioscintigraphic Demonstration of Unsuspected Urine Extravasation
Authors: T BOCCHINI, W WILLIAMS, D PATTON
Journal: Clinical Nuclear Medicine (1989)

Three cases of unsuspected urine extravasation first detected by radionuclide scintigraphy are presented with subsequent confirmation by CT and, retrograde pyelograms. A renal study done to rule out acute transplant rejection demonstrates gallbladder uptake which was initially thought to be consistent with urine extravasation.
Anatomy and function of the heart and intrathoracic vessels in congenital heart disease: Evaluation with the dynamic spatial reconstructor
Authors: Lawrence J. Sinak, Yun-He Liu, Michael Block, Douglas D. Mair, Paul R. Julsrud, Eric A. Hoffman, Donald J. Hagler, James B. Seward, Erik L. Ritman
Journal: Journal of the American College of Cardiology (1985)
Heroin Inhalation and Progressive Spongiform Leukoencephalopathy
Authors: Arnold R. Kriegstein, Beth A. Armitage, Peter Y. Kim
Journal: New England Journal of Medicine (1997)

To the Editor: We report two cases of a progressive spongiform leukoencephalopathy that, to our knowledge, has not been reported previously in the United States. The disease occurred after the patients inhaled heated heroin vapor, a practice known as “chasing the dragon.” In Patient 1, a 21-year-old woman with a six-month history of inhaling heroin vapor, progressive bradykinesia, ataxia, and slurred speech developed over a two-week period. She denied using intravenous drugs. On admission she had abulia. She followed simple, one-step commands, but there was a long period of latency before she initiated movements, which were slow and ataxic. She . . .
Abstract 2545: Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in Chinese.
Authors: Hongbing Shen, Jing Dong, Guangfu Jin, Minjie Chu, Dongxin Lin, Zhinbin Hu
Journal: Cancer Research (2013)

Abstract Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P= 1.19×10-10]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95%CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR= 0.96, 95%CI = 0.90-1.02, P=0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population. Citation Format: Hongbing Shen, Jing Dong, Guangfu Jin, Minjie Chu, Dongxin Lin, Zhinbin Hu. Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in Chinese. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2545. doi:10.1158/1538-7445.AM2013-2545
Screening for Lung Cancer High-risk Groups
Authors: A. Kubik
Journal: BMJ (1970)

B JOURNA sister's desk in a state of asphyxia.Unfortu- nately, despite all attempts at resuscitation, he had a cardiac arrest within ten minutes and failed to recover.Necropsy showed marked mediastinal emphysema, with some subcutaneous emphysema at the site of the operation.There was no possible source of this emphysema except from the wound.It seems most likely that the Yates drain allowed air to be aspirated into the wound on inspiration, particularly when the patient was lying in bed, and that expiration blocked the ends of the corrugated tubes, causing a ball-valve effect.This seems a potential risk of Yates drainage tubing which I think needs to be appreciated by all surgeons.-Iam, etc.,
Deletions of BRCA1/2 and p53 R248W gain-of-function mutation suggest impaired homologous recombination repair in fragile histidine triad-negative sebaceous gland carcinomas
Authors: K. Becker, M. Goldberg, P. Helmbold, L.M. Holbach, K.U. Loeffler, W.G. Ballhausen
Journal: British Journal of Dermatology (2008)

Sebaceous gland carcinomas represent rare malignancies of the skin and some 60% of them demonstrate high-grade microsatellite instability on the background of a defective mismatch repair system. However, a significant fraction of periocular sebaceous gland carcinomas exhibits microsatellite stability associated with a frequent loss of the candidate tumour suppressor fragile histidine triad (FHIT).We hypothesized that in those sebaceous gland carcinomas with microsatellite stability and loss of FHIT, effector molecules participating in homologous recombination repair (HRR), such as BRCA1/2, could be somatically inactivated.A pilot series of 10 paraffin-embedded sebaceous gland carcinoma specimens with a defined FHIT status was studied for loss of heterozygosity (LOH) events in the genes BRCA1, BRCA2, FHIT and WWOX. We sequenced the coding exons 5-8 of the p53 gene.Sebaceous gland carcinomas with FHIT negativity displayed LOH and biallelic deletions of the BRCA1 gene in five of 10 (50%) of the sebaceous gland carcinoma specimens analysed. Tumour-specific genomic losses close to BRCA2 were also uncovered. A homozygous p53 R248W gain-of-function mutation as the result of a CGG to TGG transition was identified in one of seven sebaceous gland carcinomas. It has been demonstrated previously that p53 R248W mutants inactivate ATM-directed HRR. This particular sebaceous gland carcinoma presented with concomitant genomic deletions at the BRCA1 and BRCA2 loci, and also at the constitutively fragile sites FRA3B/FHIT and FRA16D/WWOX.Our study demonstrates for the first time that microsatellite-stable FHIT-negative sebaceous gland carcinomas accumulate mutations that target central components of the HRR network. This observation will prompt investigations in synthetic lethality of BRCA-deficient sebaceous gland carcinomas by therapeutic poly(ADP-ribose) polymerase inhibitors.
Gastric emptying of solid meals in diabetics.
Authors: J H Scarpello, D C Barber, R V Hague, D R Cullen, G E Sladen
Journal: BMJ (1976)

The gastric emptying rate of an isotopically labelled solid meal was compared in 29 insulin-dependent well-controlled diabetics and 18 normal controls. The diabetics were assessed for evidence of autonomic neuropathy. No significant difference in gastric emptying rate was found between controls and diabetics with or without autonomic neuropathy. Only three diabetics had greatly delayed gastric emptying, but in one of these the test had given a normal result on an earlier occasion.
Acquired Methemoglobinemia Due to Ingestion of Acetophenetidin
Authors: Jean D. Ross, Richard F. Ciccarelli
Journal: New England Journal of Medicine (1962)

THE increased susceptibility of small infants to methemoglobin-forming agents is well known.1 2 3 4 5 The purpose of this paper is to report a case of methemoglobinemia in an infant after accidental ingestion of a common proprietary compound containing phenacetin, acetylsalicylic acid and caffeine, and to present studies of the mechanism of the disorder.Case ReportK.T., a 10-week-old female infant of Irish-English-French ancestry, had been well until 6 hours before admission, when her mother noticed a white powder in and about the child's mouth and discovered that she had been given 3 tablets of the compound mentioned above by a 2-year-old sibling. . . .
Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C
Authors: Ester Vanni, Maria Lorena Abate, Elena Gentilcore, Ingrid Hickman, Roberto Gambino, Maurizio Cassader, Antonina Smedile, Ele Ferrannini, Mario Rizzetto, Giulio Marchesini, Amalia Gastaldelli, Elisabetta Bugianesi
Journal: Hepatology (2009)

Abstract Chronic hepatitis C (CHC) has been associated with type 2 diabetes and insulin resistance, but the extent of impairment in insulin action, the target pathways involved, and the role of the virus per se have not been defined. In this study, we performed a euglycemic hyperinsulinemic clamp (1 mU · minute −1 · kg −1 ) coupled with infusion of tracers ([6,6- 2 H 2 ]glucose, [ 2 H 5 ]glycerol) and indirect calorimetry in 14 patients with biopsy-proven CHC, who were selected not to have any features of the metabolic syndrome, and in seven healthy controls. We also measured liver expression of inflammatory cytokines/mediators and tested their association with the metabolic parameters. Compared to controls, in patients with CHC: (1) total glucose disposal (TGD) during the clamp was 25% lower ( P = 0.003) due to impaired glucose oxidation ( P = 0.0002), (2) basal endogenous glucose production (EGP) was 20% higher ( P = 0.011) and its suppression during the clamp was markedly reduced ( P = 0.007), and (3) glycerol appearance was not different in the basal state or during the clamp, but lipid oxidation was less suppressed by insulin ( P = 0.004). Lipid oxidation was higher in patients with CHC who had more steatosis and was directly related to EGP, TGD, and glucose oxidation. The decreased insulin-stimulated suppression of EGP was associated with increased hepatic suppressor of cytokine signaling 3 (SOCS3; P &lt; 0.05) and interleukin-18 ( P &lt; 0.05) expression. Conclusion: Hepatitis C infection per se is associated with peripheral and hepatic insulin resistance. Substrate competition by increased lipid oxidation and possibly enhanced hepatic expression of inflammatory cytokines/mediators could be involved in the defective glucose regulation. (Hepatology 2009.)
Ethiquinium Chloride, an Asymmetric Bisquaternary Ammonium Salt, in the Therapy of Hypertension
Authors: Burton M. Cohen
Journal: New England Journal of Medicine (1957)

EXPERIENCE accumulated with the use of hypotensive agents over the past decade has suggested that prolonged, meticulous pharmacotherapy may be associated with an alteration in the basic process causing hypertension.1 These data have prompted the conviction that every patient with documented high blood pressure should be offered a trial of therapy.2 "Chemical sympathectomy" with hexamethonium and pentolinium derivatives has attracted particular attention among the various modalities of treatment. Structurally, these compounds are symmetric bisquaternary ammonium salts, and their efficacy led to the exploration of possible vasodepressor properties of the closely related asymmetric bisquaternary ammonium compounds, of which chlorisondamine3 is the . . .
The Therapeutic Potential of Hepatocyte Growth Factor to Sensitize Ovarian Cancer Cells to Cisplatin and Paclitaxel <i>In vivo</i>
Authors: Chiara Bardella, Daniela Dettori, Martina Olivero, Nadia Coltella, Massimiliano Mazzone, Maria Flavia Di Renzo
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Advanced ovarian cancers are initially responsive to combinatorial chemotherapy with platinum drugs and taxanes but, in most cases, develop drug resistance. We recently showed that, in vitro, hepatocyte growth factor (HGF) enhances death of human ovarian cancer cell lines treated with cisplatin (CDDP) and paclitaxel. The present study addresses whether in vivo HGF makes ovarian carcinoma cells more responsive to these chemotherapeutics. Experimental Design: Using Lentiviral vectors carrying the HGF transgene, we transduced SK-OV-3 and NIH:OVCAR-3 ovarian carcinoma cell lines to obtain stable autocrine and paracrine HGF receptor activation. In vitro, we assayed growth, motility, invasiveness, and the response to CDDP and paclitaxel of the HGF-secreting bulk unselected cell populations. In vivo, we tested the cytotoxic effects of the drugs versus s.c. tumors formed by the wild-type and HGF-secreting cells in immunocompromised mice. Tumor-bearing mice were treated with CDDP (i.p.) and paclitaxel (i.v.), combined in different schedules and doses. Results: In vitro, HGF-secreting cells did not show altered proliferation rates and survival but were strongly sensitized to the death triggered by CDDP and paclitaxel, alone or in combination. In vivo, we found a therapeutic window in which autocrine/paracrine HGF made tumors sensitive to low doses of the drugs, which were ineffective on their own. Conclusions: These data provide the proof-of-concept that in vivo gene therapy with HGF might be competent in sensitizing ovarian cancer cells to conventional chemotherapy.