tbuckley/cabot-search huggingface dataset:
Abstract 1761: Anti-tumor activity of trastuzumab-DM1 in combination with pertuzumab in a gastric cancer model
Authors: Yoriko Yamashita-Kashima, Kaori Fujimoto-Ouchi
Journal: Cancer Research (2011)

Abstract Objective: Anti-HER2 therapy is considered to be important for gastric cancer as well as breast cancer. In a previous study, we showed the combinational efficacy of trastuzumab and pertuzumab (an anti-HER2 antibody which binds a different HER2 domain from trastuzumab) in HER2-positive gastric cancer models (AACR, 2010). In the present study, we investigated the usefulness of a HER2 antibody-cytotoxic drug conjugate, trastuzumab-DM1 (T-DM1) as monotherapy and in combination with pertuzumab for HER2-positive gastric cancer as a novel therapy. Methods: A HER2 over-expressing human gastric cancer, NCI-N87 mouse xenograft model was used for examining the efficacy. T-DM1 was administered intravenously once every 3 weeks. Pertuzumab was administered intra-peritoneally once a week. Tumor growth inhibition (TGI) after 6 weeks of treatment was determined from tumor volume measurements. Apoptosis activity was measured with the activity of caspase 3/7. To measure ADCC activity, a real-time cell analyzer was used. Results: T-DM1 (1.25, 2.5, 5, 10, 20, 40 or 80 mg/kg) as monotherapy showed tumor growth inhibition dose-dependently in the NCI-N87 model. The maximum effective dose was 10 mg/kg and TGI on day 42 after treatment started was 113%. T-DM1 (5 mg/kg) in combination with pertuzumab (40 mg/kg) in the NCI-N87 model showed significantly potent anti-tumor activity with a TGI of 113%. Both T-DM1 and pertuzumab as monotherapies showed significant anti-tumor activity, their TGI were 79% and 47%, respectively. To examine the mechanism of action of the combination of T-DM1 and pertuzumab, we analyzed apoptosis of NCI-N87 cells after treatment with T-DM1, pertuzumab or both under stimulation of EGF or heregulin. 24 h after treatment, the combination group had significantly enhanced caspase 3/7 activity compared with the monotherapy groups. We also examined ADCC activity of these agents. Both T-DM1 and pertuzumab showed ADCC activity and that activity was enhanced by the combination. Conclusion: In this study, we showed that T-DM1 as monotherapy has significant anti-tumor activity in a mice model of HER2-positive gastric cancer. Furthermore, combining T-DM1 with pertuzumab significantly enhanced the anti-tumor activity compared with the efficacy of each agent used in monotherapy. The mechanism of this combination might be the potentiation of apoptosis induction and ADCC activity. The present study suggests that T-DM1 as monotherapy and in combination with pertuzumab would provide benefit for patients with HER2-positive gastric cancers. 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 1761. doi:10.1158/1538-7445.AM2011-1761
Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance.
Authors: C A Brass, J Narciso, J L Gollan
Journal: Journal of Clinical Investigation (1991)

It has been widely proposed that conversion of xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD), underlies ischemic/reperfusion injury, although the relationship of this conversion to hypoxia and its physiologic control have not been defined. This study details the time course and control of this enzymatic interconversion. In a functionally intact, isolated perfused rat liver model, mean % XOD activity increased as a function of both the duration (25 to 45% in 3 h) and degree (r = 0.97) of hypoxia. This process was markedly accelerated in ischemic liver by an overnight fast (45 vs. 30% at 2 h), and by imposing a short period of in vivo ischemia (cardiopulmonary arrest 72%). Moreover, only under these conditions was there a significant rise in the XOD activity due to the conformationally altered XDH molecule (XODc, 18%), as well as concomitant morphologic injury. Neither circulating white blood cells nor thrombosis appeared to contribute to the effects of in vivo ischemia on enzyme conversion. Thus, it is apparent that conversion to the free radical-producing state, with high levels of XOD activity and concurrent cellular injury, can be achieved during a relatively short period of hypoxia under certain well-defined physiologic conditions, in a time course consistent with its purported role in modulating reperfusion injury. These data also suggest that the premorbid condition of organ donors (e.g., nutritional status and relative state of hypoxia) is important in achieving optimal organ preservation.
Clients on diets
Authors: G. Dunea
Journal: BMJ (2001)

So we worry about frightful epidemics, on television and in the newspapers, about the Black Death coming back or variola major rising from the dead, forgetting, in the midst of our recent preoccupations, about the deadliest scourge of all, more lethal than handguns and automobiles and anthrax all put together. It is food, food, the stuff that in the Hindu Kush we drop from planes in yellow packages but that here is a pathogen, causing this terrible epidemic …
The HPRT short-term assay in monitoring individuals exposed to genotoxic agents.
Authors: R Montero, M E Gonsebatt, L A Herrera, E Rojas, P Ostrosky-Wegman
Journal: Environmental Health Perspectives (1993)

This paper reviews several monitoring studies where the short-term HPRT assay has been applied. The original method uses autoradiography to detect 3H-thymidine incorporation in variant cells that have undergone DNA synthesis; the bromodeoxyuridine modification employs this thymidine analog and fluorescence plus Giemsa staining. The studies discussed here were accomplished with either of these methods. methods. Exposures analyzed include radiation and chemotherapy as medical treatments and accidental exposures to radiation; these studies have been useful in the validation of the assay because radiation and anticancer drugs are well-known mutagens. Other potential mutagens such as environmental arsenic and a parasitic infection and praziquantel, used for its treatment, have also been monitored for hprt locus mutation. An overview of the results obtained with different agents and routes of exposure is presented here as well as some methodological aspects for the optimization of the assay for monitoring studies.
The H1 histamine receptor regulates allergic lung responses
Authors: Paul J. Bryce, Clinton B. Mathias, Krista L. Harrison, Takeshi Watanabe, Raif S. Geha, Hans C. Oettgen
Journal: Journal of Clinical Investigation (2006)

Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R–/– mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R–/– mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R–/– mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR. Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R. In vivo, allergen-specific WT but not H1R–/– CD4+ T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R–/– T cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.
Ligation of Inferior Vena Cava for Thromboembolism
Authors: Elias Amador
Journal: JAMA (1968)

The correlation between surgically related mortality and preoperative condition or degree of heart failure was studied in 119 patients who had undergone ligation of the inferior vena cava for the treatment of thromboembolism. There were 18 related deaths (15%), of which 12 (10%) were associated with a poor or terminal preoperative condition, or class 4 heart failure. In patients with class 4 heart failure, related mortality was 55%, whereas in those with lesser degrees of heart failure, related mortality was 10%. When patients with class 4 heart failure were excluded from the analysis, the mortality in patients with and without heart failure was comparable (10% vs 7%). Pulmonary emboli were found in 31 of the 37 autopsies, a preoperative diagnostic accuracy of 84%. Autopsy revealed recurrence of pulmonary emboli after ligation in 3 of the 37.
Antibiotic Activity in Surgical Incisions
Authors: Hiram C. Polk
Journal: JAMA (1980)

Perioperative antibiotic administration to produce systemic effects reduces the frequency of operative wound infection in selected procedures. Controlled clinical trials now indicate that cephalothin sodium may not be effective in this role, whereas cephaloridine and cefazolin sodium have been beneficial. Review of estimates of incisional antibiotic concentrations taken during prospective patient studies display patterns compatible with these data. EAch drug reaches acceptable incisional concentrations, which are relatively well maintained for cephaloridine and cefazolin; cephalothin disappears from human incisions so rapidly as to provide little wound protection in operations lasting more than one hour.
RELATION BETWEEN THE GENERAL NERVOUS SYSTEM AND SYMPTOMS OF "D.A.H." IN NEURASTHENIC PATIENTS
Authors: H. W. Davies, J. G. Priestley
Journal: BMJ (1919)

NEURASTHENIC PATIENTS.[ ( TI SoIT over the end of the lever-a rather awkward contretenzps in the middle of an operation.The instrument can also be used as a haemostatic guillotine, and left in situ for five minutes, as advocated by La Force.I find by the method above described that while in the vast majority of the cases removal of the tonsil is com- plete, there is no greater amount of sloughing of the bed of the tonsil taan when a sharp blade with cutting edge is used.The loss of blood is markedly lessened, as also the risk of serious haemorrhage.The amount of blood swallowed is reduced to a minimum.Tlhe sister in charge of my recovery wards is quite clear that post-operative sickness is lessened, and in cons-b quence, where patients have to go home the same day, as in lhospital practice is often unfortunately necessary, they are sooner fit for removal.
Reversal of multifocal cutaneous lymphoproliferative disease associated with Epstein-Barr virus after withdrawal of methotrexate therapy for rheumatoid arthritis
Authors: Annabel Maruani, Ewa Wierzbicka, Marie-Christine Machet, Myriam Abdallah-Lotf, Anne de Muret, Laurent Machet
Journal: Journal of the American Academy of Dermatology (2007)
Clinical Characteristics and Outcome of 467 Patients With a Clinically Recognized Eating Disorder Identified Among 52,215 Patients With Type 1 Diabetes: A Multicenter German/Austrian Study
Authors: Nicole Scheuing, Béla Bartus, Gabriele Berger, Holger Haberland, Andrea Icks, Burkhild Knauth, Nicole Nellen-Hellmuth, Joachim Rosenbauer, Martin Teufel, Reinhard W. Holl
Journal: Diabetes Care (2014)

To compare clinical characteristics and outcome of type 1 diabetes mellitus (T1DM) between patients with and without a clinically recognized eating disorder (ED).A total of 52,215 T1DM patients aged 8 to <30 years from the prospective diabetes data acquisition system DPV were analyzed. A total of 467 patients had an additional diagnosis of ED according to DSM-IV criteria (anorexia nervosa [AN], n = 141 [female: 94.3%]; bulimia nervosa [BN], n = 62 [90.3%]; and EDs not otherwise specified, including binge-eating disorder [EDNOS], n = 264 [74.2%]). Groups were compared using multivariable regression. Cox proportional hazard ratios were calculated for the association between ED and retinopathy.After adjustment for age, sex, and duration of diabetes, patients with ED revealed higher HbA1c (no ED vs. AN, BN, or EDNOS, respectively: 8.29 ± 0.01% [67.1 ± 0.1 mmol/mol] vs. 8.61 ± 0.15% [70.6 ± 1.6 mmol/mol], 9.11 ± 0.23% [76.1 ± 2.5 mmol/mol], or 9.00 ± 0.11% [74.9 ± 1.2 mmol/mol]) and a higher rate of pathological insulin injection sites (48.4 vs. 64.3, 64.1, or 62.1%). Furthermore, ketoacidosis (5.7 ± 0.1 vs. 12.1 ± 2.1, 18.0 ± 4.1, or 12.9 ± 1.6 events per 100 person-years) and hospitalization (54.9 ± 0.3 vs. 89.3 ± 6.0, 132.0 ± 12.7, or 91.0 ± 4.4 per 100 person-years) were more common, and duration of hospital stay was longer (4.81 ± 0.01 vs. 11.31 ± 0.21, 18.05 ± 0.48, or 8.44 ± 0.13 days per year). All P values were <0.05. Patients with BN and EDNOS had a 2.5-fold (95% CI 1.3-4.8) and a 1.4-fold (0.8-2.3) higher risk for retinopathy, whereas AN patients had no increased risk (0.9 [95% CI 0.4-2.3]).Diabetes health care professionals should be aware of comorbid EDs in pediatric/young-adult T1DM patients. An ED diagnosis is associated with worse metabolic control and higher rates of diabetes complications.
What's new this month in BMJ Journals
Authors: Harvey Marcovitch
Journal: BMJ (2004)

A newly developed formulation of diclofenac as an adhesive patch was used in a randomised controlled trial to treat 120 sportsmen and women within three hours of an acute impact injury. By one week, 73% of “patch” patients reported pain resolution compared with fewer than 7% of controls. No systemic adverse events were disclosed, consistent with the patch producing plasma levels of the drug several orders of magnitude lower than standard oral therapy. Minor rashes and irritation were similar in the two groups. The investigators, including representatives of the manufacturers, conclude that diclofenac patches might prove useful for rapid alleviation of pain and limitation of function in sports injuries.

Br J Sports Med 2004;38: 318-23

Three young people …
A METHOD FOR THE QUANTITATIVE DETERMINATION OF FECAL BACTERIA
Authors: H. A. Mattill, P. B. Hawk
Journal: The Journal of Experimental Medicine (1911)

From results of which the foregoing data form a part, it appears that the amount of bacterial nitrogen in the feces is a valuable index to intestinal conditions, and the method herein described is a simple and satisfactory one for making this determination. It involves three serial centrifugalizations of a two gram sample of the fresh feces brought into suspension in 0.2 per cent. hydrochloric acid. The bacterial suspension finally obtained is concentrated and extracted by alcohol, and nitrogen is determined in the precipitated material. The complete data on a given stool can be obtained in about five days, and one operator can take care of three or four stools in duplicate in one day. On an absolutely uniform diet of simple and easily digested food during a period of three to four weeks, the average amount of bacterial nitrogen in two subjects was found to be 53.9 per cent. of the total fecal nitrogen, and this percentage, though higher than that obtained by workers heretofore, is probably more nearly a true value for bacterial nitrogen, because no ether extraction was employed. The average daily amount of dry bacteria, calculated on the basis of the nitrogen values, is 8.27 grams.
A prodrug strategy to deliver cisplatin(IV) and paclitaxel in nanomicelles to improve efficacy and tolerance
Authors: Haihua Xiao, Haiqin Song, Qiang Yang, Haidong Cai, Ruogu Qi, Lesan Yan, Shi Liu, Yonghui Zheng, Yubin Huang, Tongjun Liu, Xiabin Jing
Journal: Biomaterials (2012)
P3-128: Correlation of the epidermal growth factor receptor mutations with clinical outcomes in patients with non–small cell lung cancer treated gefitinib: an exploratory molecular analysis of a prospective phase II study
Authors: Hyewon Lee, Hoyong Sim, Se Hoon Park, Jinny Park, Eun Kyung Cho, Dong Bok Shin, Jae Hoon Lee, Jae-Ik Lee, Seung Yeon Ha
Journal: Journal of Thoracic Oncology (2007)
New debate for Dutch health care
Authors: T Sheldon
Journal: BMJ (1994)

Plans to take a second look at the stringent financial controls proposed on Dutch health care were revealed in the state opening of parliament last week. They have been hailed as a breakthrough by health care organisations, which feared draconian cuts if a 1.3% ceiling on increased spending was adhered to rigidly.

The move is seen as the first sign of a new debate on Dutch health care, which for years has concentrated solely on cost rather than care. And it is viewed as a good start for new …
Changes in Public Attitudes on Narcotic Addiction
Authors: E. MANSELL PATTISON, LYALL A. BISHOP, ARNOLD S. LINSKY
Journal: American Journal of Psychiatry (1968)

By sampling articles on narcotic addiction from the popular magazines over the past seven decades, the authors investigated trends in public attitudes toward the narcotic addict. In comparison with the public view in 1900, the addict is now seen as less responsible for his behavior, and the social milieu is given greater significance. Public recommendations about coping with the problem of addiction have shifted in emphasis from punitive methods to medical treatment and social rehabilitation. These findings are consistent with concurrent changes in the popular view of the nature of man.
Obesity and Hypertension
Authors: HARRIET P. DUSTAN
Journal: Annals of Internal Medicine (1985)

Obesity and hypertension are closely associated. Hypertension occurs frequently in industrialized populations that gain weight with advancing age, and is infrequent in primitive populations that are not obese. There are two reasons for concern about the relationship of obesity to hypertension. Weight gain in young adult life is a potent risk factor for later development of hypertension. Weight reduction in obese hypertensive persons often reduces arterial pressure. Mechanisms of obesity hypertension are as yet unidentified; an earlier hypothesis that it is related to salt intake has not been supported by recent studies. Hemodynamic studies have shown that obesity is associated with an elevated cardiac output and expanded blood volume; in normotensive obese persons peripheral vascular resistance is reduced, and in hypertensive persons it is normal or elevated. Studies of hormonal and neural factors have failed to explain the presence of hypertension in some obese persons and its absence in others.
THE IMPORTANCE OF PRESERVING THE INTEGRITY OF CONTIGUOUS STRUCTURES WHEN OPERATING ON THE TONSILS
Authors: C. M. HARRIS
Journal: JAMA (1913)

beat more slowly, or lessen the excitability of the heart muscle, which would produce the same result.Again.Ibis slowing of the heart may be due to a reflex inhibition of the augmentor nerves of the hear).This inhibition may be brought about by the irritative ait ion on the intestinal wall of the strong cathartics u^<<\.The nervous mechanism of the intestines is inti¬ mately connected with the sympathetic system through the splanchnic nerves, and through these the rellex inhibition is brought about.
Dermatofibrosarcoma protuberans: A clinicopathological, immunohistochemical, genetic ( COL1A1-PDGFB ), and therapeutic study of low-grade versus high-grade (fibrosarcomatous) tumors
Authors: Beatriz Llombart, Carlos Monteagudo, Onofre Sanmartín, José Antonio López-Guerrero, Carlos Serra-Guillén, Andrés Poveda, Esperanza Jorda, Antonio Fernandez-Serra, Antonio Pellín, Carlos Guillén, Antonio Llombart-Bosch
Journal: Journal of the American Academy of Dermatology (2011)
Poor people view hospitals as providing better access, care, and social support
Authors: M. McCarthy
Journal: BMJ (2013)

Many urban poor people prefer going to hospital for care rather than a doctor’s office because they perceive hospital care as less expensive, more accessible, and of higher quality, and because hospitals provide social and emotional support that many of these patients lack in the community, says a study in the current issue of the journal Health Affairs.1

Researchers interviewed 40 low income hospital patients from poor neighborhoods in Philadelphia, Pennsylvania. The participants were also selected to create two patient profiles: those who reported five or more acute care episodes in the previous six months, Profile A; and those who had one to four episodes, Profile B.

The study’s lead author was Shreya Kangovi, a Robert Wood Johnson Foundation Clinical Scholar in the department of medicine at the Philadelphia Veterans Affairs Medical Center.

Twelve men and 28 women participated in the study. Their average age was 42.2, standard deviation 14.5, and 90% were African American.

The researchers said, “Most participants perceived two main benefits of hospital care relative to ambulatory care: better overall access across a variety of domains and higher levels of trust in the technical quality of hospital providers and services.”

Just making appointments with a …
The Runaway American Health Care System
Authors: John W. Burnside
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Two articles in a recent issue of<i>JAMA</i>contain the same misstatement, which detracts from the otherwise thoughtful comments of the authors. Drs Davies and Felder<sup>1</sup>state that "by the year 2000 health care will consume 17% of the gross national product." Dr Lundberg<sup>2</sup>in his editorial uses the phrase "ever-increasing percent of our gross national product that is consumed for medical and health care." The gross national product is the sum of all the goods and services in the economy. It is not an independent allocation of money that can be consumed or used up. The statement that health care consumes the gross national product leads to the belief that absent the health care industry, there would be a large piece of the gross national product that could be used for other things. On the contrary, without health care the gross national product would
Treatment of Hepatocellular Carcinoma in the Community: Disparities in Standard Therapy
Authors: Linda C. Harlan, Helen M. Parsons, Charles L. Wiggins, Jennifer L. Stevens, Yehuda Z. Patt
Journal: Liver Cancer (2015)

Hepatocellular carcinoma (HCC) incidence is expected to rise dramatically over the next decades because of increasing hepatitis C infections and obesity-related comorbidities. However, little information exists regarding the treatment of patients with HCC in the community setting. The purpose of this article was to characterize patterns of diagnosis, treatment, and survival for HCC in the community.We identified 946 HCC patients in the 2007 National Cancer Institute's Patterns of Care study. Chi-square analyses and multivariable regression were used to examine patient and provider factors associated with treatment and survival by stage at diagnosis.Our primary findings indicate that liver transplants, embolization, or radiofrequency ablation for Barcelona Clinic Liver Cancer stage A patients were performed significantly less often for non-Hispanic blacks, Hispanics, patients in the highest income quartile, and patients with Medicaid. Patients with stage D disease were less likely to receive cancer therapy if they had Medicaid insurance compared to private insurance (p<0.001 for all). In multivariable analyses, all-cause mortality was associated with treatment in a hospital without a residency training program (hazard ratio [HR] 1.4 [1.1,1.9]), more advanced stage (HR: 10.6 [5.7, 19.5] stage D vs. A), and lack of appropriate treatment (HR: 2.4 [1.9,3.2]).This is the first population-based study to evaluate therapy provided for HCC in the community. Current therapy depended on patients' HCC stage at diagnosis and other clinical and demographic factors. Overall, our study identifies those least likely to receive specific therapies in a variety of health care settings and can inform strategies for promoting appropriate therapy now and as new agents are developed.