tbuckley/cabot-search huggingface dataset:
Porphyrin metabolism and haem biosynthesis in Gilbert's syndrome.
Authors: K E McColl, G G Thompson, E el Omar, M R Moore, A Goldberg
Journal: Gut (1987)

Studies in 14 patients with unconjugated hyperbilirubinaemia caused by Gilbert9s syndrome have revealed abnormalities of the enzymes of haem biosynthesis measured in peripheral blood cells. The activity of the penultimate enzyme of haem biosynthesis protoporphyrinogen (PROTO) oxidase was reduced at 3.1 +/- 2.6 nmol PROTO/g protein/h (mean +/- ISD) compared with 8.2 +/- 5.1 in controls (p less than 0.005). This was associated with a compensatory increase in the activity of the initial and rate controlling enzyme of the pathway delta-aminolaevulinic acid (ALA) synthase at 866 +/- 636 nmol ALA/g/protein/h compared with 156 +/- 63 in controls (p less than 0.001). Unlike variegate porphyria in which there is a genetic deficiency of PROTO oxidase there was no increased excretion of porphyrins or their precursors in Gilbert9s syndrome. Accentuation and subsequent correction of the unconjugated hyperbilirubinaemia with rifampicin produced reciprocal changes in PROTO oxidase activity indicating that bilirubin may be inhibiting the activity of this enzyme.
Abstract IA8: The interplay of inflammation and cancer.
Authors: Glenn Dranoff
Journal: Cancer Research (2013)

Abstract Efficacious cancer immunotherapies will likely require combinations of strategies that enhance tumor antigen presentation and antagonize negative immune regulatory circuits. We demonstrated that vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF followed by antibody blockade of CTLA-4 accomplishes clinically significant tumor destruction with minimal toxicity in a majority of stage IV metastatic melanoma and some advanced ovarian carcinoma patients. The detailed analysis of patients achieving sustained clinical benefits from these therapies illustrated the importance of a coordinated cellular and humoral anti-tumor immune response. Indeed, the extent of tumor necrosis in post-treatment biopsies was linearly related to the natural logarithm of the ratio of infiltrating CD8+ effector T cells to FoxP3+ Tregs. Moreover, therapy induced a potent antibody response to several key tumor cell surface and secreted proteins; these antibodies manifest functional activity in vitro, antagonizing tumor cell survival, invasive potential, and angiogenesis. Through an analysis of cytokine deficient mice, we delineated a critical role for GM-CSF in Treg homeostasis. GM-CSF is required for the expression of the phosphatidylserine binding protein MFG-E8 in antigen presenting cells, whereas the uptake of apoptotic cells by phagocyte-derived MFG-E8 maintains peripheral Treg activity. While blockade of MFG-E8 can enhance therapeutic immunity in the context of cancer vaccines, loss of Treg homeostasis with MFG-E8 deficiency can lead to chronic inflammation. Mice deficient in GM-CSF and IFN-γ develop at high frequency germinal center derived lymphomas and nonsmall cell lung carcinomas. The pathogenesis of these tumors reflects a combination of tumor-promoting inflammation and a loss of protective tumor immunity. Taken together, these findings highlight dual roles for immunity in cancer pathogenesis and therapy. Citation Format: Glenn Dranoff. The interplay of inflammation and cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA8.
Determining Issues of Importance for Patients with Breast Cancer: Results of a Web-Based Study in 1072 Patients To Enhance the Content Validity for the Development of a New Health-Related Quality of Life (Ql) Instrument, the Breast Cancer Symptom Scale (BCSS).
Authors: L. Weiselberg, R. Gralla, J. Horigan, B. Davis, P. Hollen, J. Petersen, K. Burg, A. Belland
Journal: Cancer Research (2009)

Abstract Background:Identifying key issues for patients with malignancy is central to assessing QL and patient reported outcomes during all points of the illness trajectory. The involvement of patients in establishing content validity is crucial for instrument development. The conceptual model for the BCSS focuses on areas of importance for patients (Hollen, Supp Care Ca 1994).Methods:We used the established patient base of the web-based NexCura information resource to survey registered patients with breast cancer. Demographic stratifications included disease stage, age, menopausal status, time since diagnosis, prior/current treatment with surgery, RT, chemotherapy, hormonal, targeted, and CAM approaches. 1072 patients (median age 53, 65% stage I, 43% &amp;gt; 2 years since diagnosis) completed the anonymous web-conducted survey. Patients ranked 21 issues on a 5-point scale, assessing the importance of each item. Issues included general, physical, functional, psychosocial and summative items.Results:The 9 highest ranked items are seen below. Results are described by the percent of patients choosing the top category (very important) and the top 2 importance categories. The five lowest ranked items dealt with appetite, breast-specific issues, hot flashes and sexuality. Ratings by breast cancer subsets (newly diagnosed, on treatment, NED, hormonal or non-hormonal treatment, metastatic disease, survivors) showed some differences compared with the whole group.[table1]N=1072Very ImportantVery Important +ImportantGood QL82%99%Maintaning independence75%97%Able to sleep69%97%Able to concentrate65%97%Perfrom normal activities62%97%Being fatigued61%95%Having depression51%85%Being anxious47%85%Having pain46%80% Conclusions:These results represent one of the largest surveys of concerns expressed by patients with breast cancer and support using computer-assisted technology to assess such information for rapid input of large patient samples. This study gives strong support for content validity for the BCSS and provides data on which to base separate QL instruments for specific breast cancer settings. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5048.
Improvement of psoriasis and cutaneous side-effects during tyrosine kinase inhibitor therapy for renal metastatic adenocarcinoma. A role for epidermal growth factor receptor (EGFR) inhibitors in psoriasis?
Authors: E. Wierzbicka, J.M. Tourani, G. Guillet
Journal: British Journal of Dermatology (2006)

Journal Article Improvement of psoriasis and cutaneous side‐effects during tyrosine kinase inhibitor therapy for renal metastatic adenocarcinoma. A role for epidermal growth factor receptor (EGFR) inhibitors in psoriasis? Get access E. Wierzbicka, E. Wierzbicka Department of Dermatology and Medical Oncology Unit, University of Poitiers Medical School, Rue de la Milétrie, BP577, 86021 Poitiers Cedex, France E‐mail: e.wierzbicka@chu‐poitiers.fr Search for other works by this author on: Oxford Academic Google Scholar J.M. Tourani, J.M. Tourani Department of Dermatology and Medical Oncology Unit, University of Poitiers Medical School, Rue de la Milétrie, BP577, 86021 Poitiers Cedex, France E‐mail: e.wierzbicka@chu‐poitiers.fr Search for other works by this author on: Oxford Academic Google Scholar G. Guillet G. Guillet Department of Dermatology and Medical Oncology Unit, University of Poitiers Medical School, Rue de la Milétrie, BP577, 86021 Poitiers Cedex, France E‐mail: e.wierzbicka@chu‐poitiers.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 1, 1 July 2006, Pages 213–214, https://doi.org/10.1111/j.1365-2133.2006.07299.x Published: 01 July 2006
The Role of Active Family Nutritional Support in Navajos’ Type 2 Diabetes Metabolic Control
Authors: Carolyn Epple, Anne L. Wright, Vijay N. Joish, Mark Bauer
Journal: Diabetes Care (2003)

OBJECTIVE—We examined if active family nutritional support is associated with improved metabolic outcomes for Diné (Navajo) individuals living with type 2 diabetes. RESEARCH DESIGN AND METHODS—The presence of family support, using variables identified in earlier ethnographic research, was assessed via surveys in a convenience sample of 163 diabetic individuals. Diabetes outcome measures (HbA1c, serum glucose, triglycerides, total cholesterol, creatinine, and systolic and diastolic blood pressure measures) were extracted from participants’ medical records. Bivariate analyses and multiple logistic regressions were conducted. RESULTS—All measures of family support showed a relation with one or more indicators of metabolic control in bivariate analyses. In multivariate analyses, respondents were more likely to be in the best tertile for triglyceride (P &amp;lt; 0.05), cholesterol (P &amp;lt; 0.05), and HbA1c (P &amp;lt; 0.05) if another person cooked most of the meals. Respondents in families who bought/cooked “light” foods were more likely to be in the best tertile for triglyceride (P &amp;lt; 0.005) and cholesterol levels (P &amp;lt; 0.005), and those in families whose members ate “light” foods with them were more likely to be in the best tertile for triglycerides (P &amp;lt; 0.005). When all three support variables were entered into a multivariate model, only the variable “other family members cook the majority of the meals” was significantly associated with being in the lowest triglyceride (P = 0.05), HbA1c (P &amp;lt; 0.05), or cholesterol tertiles (P &amp;lt; 0.05). These relationships were most evident for women with diabetes. CONCLUSIONS—Active family nutritional support, as measured by culturally relevant categories, is significantly associated with control of triglyceride, cholesterol, and HbA1c levels. The findings suggest that the family is a more useful unit of intervention for Diné individuals than for the individual alone when designing diabetes care strategies.
Rethinking Nonadherence: Historical Perspectives on Triple-Drug Therapy for HIV Disease
Authors: Barron H. Lerner
Journal: Annals of Internal Medicine (1998)

The advent of triple-drug therapy for HIV disease has raised the concern that disadvantaged patients with multiple social problems may be nonadherent to treatment. Fearing that partial adherence will lead to drug resistance, some clinicians are withholding these powerful new drugs from such patients. The historical record demonstrates that labeling patients as nonadherent may be both stigmatizing and inaccurate. Since 1900, such adjectives as ignorant, vicious, and recalcitrant have been used to describe patients who do not follow medical advice.Less judgmental terms, such as nonadherent and noncompliant, are now used, but these terms still imply that patients should obey physician-imposed regimens. Studies of nonadherence have consistently shown that the problem is widespread among all persons and cannot reliably be predicted on the basis of patient characteristics. This paper argues that physicians should deemphasize the standard approach of predicting and correcting nonadherent behavior in certain patients.Rather, clinicians should encourage all HIV-positive patients to devise individualized treatment plans that can facilitate reliable ingestion of medication. Although the potential development of resistance to triple-drug therapy remains an important public health issue, concern about this possibility must be balanced with respect for patients' rights. Encouraging the active participation of HIV-positive persons in their own treatment will help avoid judgmental and inaccurate assessments of patient behavior and may help patients take medications more successfully.
Sodium Bicarbonate in Respiratory Acidosis
Authors: Fred Plum
Journal: JAMA (1964)

<h3>To the Editor:—</h3> In an editorial (<i>JAMA</i><b>188</b>:70 [April 6] 1964), you support the recommendation by Motley that sodium bicarbonate should be administered to correct a very low serum pH in patients with carbon dioxide retention. Evidence is limited that sodium bicarbonate is beneficial under such circumstances. Theoretically at least, the procedure carries risk. Gesell and Hertzman (<i>Amer J Physiol</i><b>78</b>:610, 1926) demonstrated that intravenous sodium bicarbonate frequently produces a fall in the pH of the cerebrospinal fluid (CSF), and presumably of the brain, concurrently with the rise in serum pH. This is best explained by evidence that the bicarbonate ion does not diffuse across the blood—spinal fluid barrier, while the CO<sub>2</sub>molecule is readily diffusible. As a result, during sodium bicarbonate infusion, blood CO<sub>2</sub>increases due to dissociation; brain and spinal fluid arterial carbon dioxide pressure (pCO<sub>2</sub>) and carbonic acid increase, and CSF pH
Gall bladder function after endoscopic sphincterotomy: Authors' reply
Authors: L A Desa, P A Grace, J N Thompson, M N Vipond
Journal: BMJ (1990)

based on only six patients have doubtful statistical significance and clinical relevance.Thus it is not surprising that the conclusions drawn by the authors are not supported in the existing literature.Indeed, there is a large body of data now available attesting to the long term safety of sphincterotomy in patients with intact gall bladders.'Furthermore, there is considerable evidence that sphincterotomy may enhance gall stone clearance from the gall bladder in animals and man.For example, dynamic scintigraphic studies using cholecystokinin in dogs have shown increased ejection fractions after sphincterotomy.'Safe and effective use of endoscopic sphincterotomy of the gall bladder in a wider population can be supported only by correctly designed controlled clinical trials.
Safety of Electrical Cardioversion in Patients Without Digitalis Toxicity
Authors: ROY V. DITCHEY
Journal: Annals of Internal Medicine (1981)

To ascertain whether electrical cardioversion increases ventricular ectopy in patients receiving nontoxic doses of digitalis, we recorded continuous electrocardiograms in 21 patients for at least 1 hour before and immediately after direct-current countershock. Seventeen patients also received specific antiarrhythmic therapy. There were no consistent differences in the frequency or severity of ventricular ectopy before and after cardioversion despite a wide range of serum digoxin levels (0.1 to 3.0 ng/mL; mean, 1.6 ng/mL). No patient had ventricular tachycardia after cardioversion, and all eight patients with serum digoxin levels greater than 2.0 ng/mL had the same or fewer ventricular ectopic beats per hour and the same or lower ectopy grades after cardioversion when pre- and postshock recordings were compared. These findings suggest that patients receiving digoxin without clinical evidence of digitalis toxicity are at low risk for serious postcardioversion ventricular arrhythmias, even when serum digoxin levels are modestly elevated. The extent to which this low risk is due to concomitant antiarrhythmic therapy is unknown.
DISCHARGE INITIATION OF ACE INHIBITORS OR ARBS IS ASSOCIATED WITH SIGNIFICANTLY LOWER 30-DAY ALL-CAUSE READMISSION IN HOSPITALIZED OLDER PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION
Authors: Kumar Sanam, Vikas Bhatia, Sridivya Parvataneni, Charity Morgan, Steven Lloyd, Fadi Hage, Sumanth Prabhu, Gregg Fonarow, Wilbert Aronow, Marjan Mujib, Prakash Deedwania, Javed Butler, Michel White, Stefan Anker, Richard Allman, Ali Ahmed
Journal: Journal of the American College of Cardiology (2014)
Hepatic Disorders Associated with Liver/Kidney Microsomal Antibodies
Authors: M. G. M. Smith, R. Williams, G. Walker, M. Rizzetto, D. Doniach
Journal: BMJ (1974)

A study of the clinical associations of a recently defined tissue autoantibody, the liver/kidney microsomal (L.K.M.) antibody, showed that out of 33 patients 26 had clinical liver disease. Fifteen of the patients had active chronic hepatitis and there were seven cases of acute hepatitis, precipitated by presumed virus A infection in three instances and by drug hypersensitivity in the other four. The remaining cases with liver disease included two with subclinical hepatitis and two with hepatocellular carcinoma. Evidence is presented that the patients with active chronic hepatitis may represent a distinct subgroup of the disease with a young mean age, an even male to female ratio, and a striking lack of other nonorgan-specific autoantibodies-that is, antinuclear and smooth muscle-which are usually present in the other autoimmune variant of the disease.
Abstract 2314: The combination of DNA methylation and H3K27me3 is a cancer-specific dual epigenetic modification
Authors: Hideyuki Takeshima, Mika Wakabayashi, Naoko Hattori, Satoshi Yamashita, Toshikazu Ushijima
Journal: Cancer Research (2014)

Abstract Alterations of epigenetic modifications are promising targets of cancer therapy, and several epigenetic drugs are now used in the clinical field. At the same time, individual epigenetic modifications have physiological roles. Therefore, a cancer-specific combination of epigenetic modifications (dual modifications) is considered to be better as a therapeutic target. However, it is unclear whether or not such cancer-specific dual modification is present. In this study, we aimed to clarify whether cancer-specific dual modification is present by focusing on the combination of two major repressive modifications, DNA methylation and trimethylation of histone H3 lysine 27 (H3K27me3). DNA methylation and H3K27me3 analyses in human colon, breast, and prostate cancer cell lines by Infinium HumanMethylation450 and ChIP-on-chip, respectively, revealed that 24.7±4.1% of DNA methylated genes were co-localized with H3K27me3 in cancer cells. In contrast, only 11.8±7.1% of DNA methylated genes were co-localized with H3K27me3 in their normal counterpart cells. 29.9±17.4% of genes with the dual modifications had neither DNA methylation nor H3K27me3 in normal counterpart cells. Expression levels of genes with the dual modifications were as low as those of genes with only DNA methylation in cancer cells. Analysis of re-activation of genes with the dual modifications by a DNA demethylating reagent, 5-aza-2′-deoxycytidine (5-aza-dC), and/or an EZH2 inhibitor, GSK126, revealed that genes with the dual modifications, such as IGFBP7, SFRP1, and SLC6A15, were re-activated more efficiently by the combination treatment than by a single treatment with 5-aza-dC. In contrast, such a combination effect on gene re-activation was not observed for genes with only DNA methylation. Furthermore, the combination treatment by 5-aza-dC and GSK126 had an additive inhibitory effect on growth of cancer cells. These results showed that genes with the dual modifications, DNA methylation and H3K27me3, are increased in cancer cells, and the combination of a DNA demethylating reagent and an EZH2 inhibitor is useful for re-activation of these genes. Citation Format: Hideyuki Takeshima, Mika Wakabayashi, Naoko Hattori, Satoshi Yamashita, Toshikazu Ushijima. The combination of DNA methylation and H3K27me3 is a cancer-specific dual epigenetic modification. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2314. doi:10.1158/1538-7445.AM2014-2314
European curriculum recommendations for training in adult respiratory medicine: crossing boundaries with HERMES
Authors: R. Loddenkemper, T. Séverin, P.L. Haslam
Journal: European Respiratory Journal (2008)

reventing, curing or alleviating suffering from respiratory diseases has always been part of the European Respiratory Society's (ERS) mission.In that respect, promoting and providing state-of-the-art medical education, in order to achieve the highest possible standards of practice in respiratory medicine and to improve harmonisation of training across Europe, is a major priority for the ERS.
Opportunities Abroad for Service in Medical Education and Public Health
Authors: Guy S. Hayes
Journal: New England Journal of Medicine (1964)

THE number of opportunities for physicians to work abroad in private, governmental and international agencies has soared in recent years, and American medical schools are becoming increasingly involved. Only good can come from this sort of liaison in terms of general development to reduce the widening gap between the haves and the have-nots in the world. Equally important is the creation of a basis for genuine understanding and respect between nations.My initial professional sortie abroad occurred shortly after graduation, when I succumbed to an unexplained hankering to see the Balkans. Fortunately for any qualms I may have had about . . .
Outcome of Acute Cholecystitis in Patients with Diabetes Mellitus
Authors: DAVID F. RANSOHOFF
Journal: Annals of Internal Medicine (1987)

Prophylactic cholecystectomy has been recommended in patients who have diabetes and silent gallstones because of the reports of increased mortality resulting from acute cholecystitis in such patients. To assess recent mortality rates, we reviewed the course of acute cholecystitis in patients hospitalized between 1960 and 1981 at one hospital. Death occurred in 3 of 46 patients with diabetes and in 7 of 263 patients without the disease (p = 0.55). The age-adjusted estimate of the relative risk for death was 2.2 (95% confidence interval, 0.5 to 9.4) for diabetic compared with nondiabetic patients. All 3 diabetic patients who died had been diagnosed as having diabetes within 5 years of death, and only one had been taking insulin. Patients who had elevated blood urea nitrogen levels ( > 20 mg/dL) were found to have an increased mortality rate when compared with patients with normal levels (27% compared with 2%; p < 0.001). Results were similar for the outcome of serious complications. These results suggest the need for reconsideration of the recommendation for prophylactic cholecystectomy in diabetic patients with silent gallstones.
Urinary Bisphenol A Levels during Pregnancy and Risk of Preterm Birth
Authors: David E. Cantonwine, Kelly K. Ferguson, Bhramar Mukherjee, Thomas F. McElrath, John D. Meeker
Journal: Environmental Health Perspectives (2015)

Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB.In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB.A nested case-control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston, Massachusetts, during 2006-2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as "spontaneous," which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or "placental," which was preceded by preeclampsia or intrauterine growth restriction.Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant's sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males.These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB.Cantonwine DE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. 2015. Urinary bisphenol A levels during pregnancy and risk of preterm birth. Environ Health Perspect 123:895-901; http://dx.doi.org/10.1289/ehp.1408126.