tbuckley/cabot-search huggingface dataset:
Faecal bile acid loss and bile acid pool size during short-term treatment with ursodeoxycholic and chenodeoxycholic acid in patients with radiolucent gallstones.
Authors: G Salvioli, R Salati
Journal: Gut (1979)

Twelve non-obese patients with radiolucent gallstones were fed on a standard diet. After 10 days (period A), six patients received 15 mg/kg/day of ursodeoxycholic acid (UDCA) (group I) and the other six (group II) the same dose of chenodeoxycholic acid (CDCA) for 15 days (period B). An intravenous injection of 20 micro Ci of 14C-UDCA and of 14C-CDCA was given on the 11th day of period B to the patients of group I and II respectively. Stools were collected at the end of period A and B and one bile sample was collected on the 12th day of period B. The faecal bile acid loss was higher during chenotherapy (36.12 mumol/kg/day) than during ursotherapy (23.94 mumol/kg/day), as was the proportion of lithocholic acid (73% vs 43%) in the faeces. Decay constant rate of faecal radioactivity was 0.365 day-1 in group I and 0.642 in group II. The results indicate that faecal bile acid excretion and turnover rate are greater during CDCA than UDCA, while UDCA increases the bile acid pool size to an even greater extent than does CDCA (150.2 vs 94.9 mumol/kg). This is probably because the former is more slowly degraded to poorly reabsorbable compounds. In fact, the bile saturation index was 0.66 in group I and 1.05 in group II, even though biliary CDCA in the latter had risen to 69.6%.
Toll signals provoke plaque buildup
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

Fatty foods plug up arteries in more ways than one, according to Mullick et al., on page 373. They also trigger the expression of an innate immune receptor that makes the arteries more fat friendly.






Figure 1

A high fat diet increases the expression of Toll-like receptor 2 (green) on endothelial cells within four weeks (left to right).




Recent data suggest that the immune receptor in question, Toll-like receptor (TLR) 2, which recognizes bacterial lipids, might also enhance atherosclerosis—a disease that can lead to restricted blood flow due to the accumulation of fat in blood vessels. Mice that are plaque prone because they cannot properly dispose of fat stay plaque free if TLR2 is knocked out. Its loss from immune cells alone, however, does not protect these mice, suggesting that TLR2 on a nonimmune cell favors plaque growth.

Mullick et al. now find that TLR2 is expressed on the endothelial cells that line the curves of blood vessels. These cells are plaque prone by nature; the uneven blood flow here stimulates them to express more adhesion molecules and chemokines. They thus attract both circulating fat and macrophages that eat the fat and then harden into plaques. A high-fat diet thus increases plaque formation in part by giving macrophages more to chew on.

A high-fat diet also increased endothelial TLR2 levels in the atherosclerosis-prone mice, the authors found. Components of dietary fat may bind to TLR2 and thereby increase expression of the receptor on endothelial cells. These mice accumulated larger fat deposits and more macrophages in vessel curves than did their TLR2-deficient counterparts. The team has yet to determine how TLR2 expands plaques. Perhaps, like uneven blood flow, it increases endothelial cell adhesion molecule or chemokine levels.
Should there be a moratorium on the use of cholesterol lowering drugs?
Authors: G. Davey Smith, J. Pekkanen
Journal: BMJ (1992)

2][3][4] The degree of disagreement is surprising as they review essentially the same data, from clinical trials of cholesterol lowering by drugs or by diet.There is agreement about a reduced risk for coronary events, but there are differing interpretations of the increase in mortality from non-cardiovascular causes that has generally been seen.Particular concern was generated by a recent meta-analysis that showed a significantly increased risk of death from accidents and violence when the results of six randomised primary prevention trials were pooled.3Despite the uncertainty an aggressive approach to cholesterol reduction features in most of the official guidelines for the primary prevention of coronary heart disease.`InBritain the introduction of the new general practitioner contract, with its focus on health promotion, is likely to result in an increase in cholesterol testing.High percentages of the British population would become candidates for drug treat- ment if the guidelines currently advanced by some authorities were put into practice.For middle aged men and women with other coronary risk factors the European Atherosclerosis Society recommends a cut off level, above which the use of lipid lowering drugs should be considered,6 well below the mean population cholesterol concentration.0`'2The entry criteria for the expanded clinical evaluation of lovastatin study (EXCEL)"5 would include a third of the British population.
Ongoing Care of Patients After Primary Treatment for Their Cancer
Authors: H. Kattlove, R. J. Winn
Journal: CA A Cancer Journal for Clinicians (2003)

Nearly nine million people living in the United States have had a diagnosis of cancer. As the population ages, this number will increase. Most of these people will need follow-up care to deal with problems related to their cancer. Depending on the cancer, they may or may not benefit from surveillance to detect recurrence. Most will be more likely than average to develop a second primary cancer. Some will be genetically susceptible to another type of cancer. Many will have complications from their treatment that need attention. Also, their treatment may have altered certain physiologic functions. Finally, many will have suffered psychosocial difficulties either as a result of their cancer or its treatment. This article deals with these issues for the most commonly encountered cancers. Its major goal is to alert physicians to be aware of and help them to deal with these issues. Clearly, such an ambitious goal can only be partly achieved in a single journal article. Hopefully, the references included will allow physicians to proceed further if they wish.
There but fortune
Authors: Karen E. Victor
Journal: Annals of Internal Medicine (1996)

Ad Libitum15 October 1996There but fortuneKaren E. Victor, MDKaren E. Victor, MDBoston, MA 02215Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-8-199610150-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail At the end of the first day of the Society of General Internal Medicine meeting in San Diego, I got into a taxi to go to my hotel. The driver was a thin, tired-looking, middle-aged man who spoke in gentle, accented English.After some talk about the weather and where I was from, I asked him how long he'd been in the States.“A year and a half,” he said.“Welcome.”“Thanks, ma'am.”He had come from Afghanistan.He asked if I was a physician, and then what the conference was about.Well, I said, it was about how to ... Author, Article, and Disclosure InformationAffiliations: Boston, MA 02215Corresponding Author: Karen E. Victor, MD, Deaconess Medical Associates, One Autumn Street, Boston, MA 02215. Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1996Volume 125, Issue 8Page: 694KeywordsAntibioticsEmergency departmentHealth insurancePenicillinPharyngitisStreptococcal infectionsSurgeons ePublished: 15 August 2000 Issue Published: 15 October 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Swiss judge orders HIV positive woman to disclose partners' names
Authors: Bojan Pancevski
Journal: BMJ (2006)

A Swiss court has ordered an HIV positive woman who had unprotected consensual sex to name all her sexual partners and to keep the list updated. It also gave her a suspended prison sentence.

HIV and AIDS support groups have criticised the court's interpretation of a Swiss law designed to combat epidemics so that it would apply to people infected with HIV. Lawyers also warned of the complicated legal issues in forcing a person to hand over such sensitive …
Abstract B17: Heat shock-induced danger signals in tumor cells are crucial for a rapid differentiation of monocyte to therapeutic dendritic cells
Authors: Raquel Aguilera, Carlos Saffie, Fermin González, Andres Tittarelli, Diego Reyes, Carlos Ferrada, Mercedes N. López, Flavio Salazar-Onfray
Journal: Clinical Cancer Research (2010)

Abstract Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that initiate a cell-mediated antitumor immune response. Recently, we showed that monocyte-derived DCs loaded with a heat-shocked melanoma cell lysate (TRIMEL®) induce melanoma-specific immune responses, thus prolonging patient survival. Here, we describe the rapid effect of TRIMEL on human monocytes differentiation to tumor-antigen presenting cells (TAPCells®). TAPCells showed a mature DC-like phenotype and effectively activated melanoma associated antigen (MAA)-specific CD4+ and CD8+ T lymphocytes. Moreover, heat shock (HS) pre-conditioning of TRIMEL composing cells increased calreticulin (CRT) cell surface translocation and released high-mobility group box 1 protein (HMGB1), which was closely associated to the induction of APC maturation and efficient MAAs cross-presentation. Finally, 26 out of 43 patients vaccinated with TAPCells showed a TRIMEL-specific delayed type hypersensitivity reaction (DTH) associated to anti-melanoma T cell recognition, reduced rates of progression and prolonged patient survival. Our results suggest that heat-shocked tumor cell lysates are optimal source of MAAs, inducing activated APCs with improved MAAs cross-presentation capacity and clinically effective immunogenicity. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B17
Abstract LB-1: PKR promotes genetic instability and evolution of MDS to acute leukemia in mice by negatively regulating DDR and DNA repair in a novel mechanism
Authors: Xiaodong Cheng, Michael Byrne, Richard Lynn Bennett, Stratford William May
Journal: Cancer Research (2014)

Abstract The interferon-inducible, dsRNA-dependent protein kinase, PKR, is reported to be involved in diverse cytoplasmic functions. However, PKR has recently been reported to be expressed in the nucleus of high-risk MDS and leukemia patients but its nuclear function is not known. We confirm that increased nuclear activated PKR does occur in AML cell lines compared to normal MEF and bone marrow stem/progenitor cells. Increased nuclear PKR is associated with impaired DNA damage response (DDR) and double strand break (DSB) repair following ionizing irradiation (IR). Knock-down and pharmacological inhibition of PKR reveals that activated nuclear PKR may function to suppress the γ-H2AX response characteristic of DDR following IR. Mechanistically, we find that nuclear PKR binds and co-immunoprecipitates with ATM in a mechanism that inhibits ATM phosphorylation. This leads to inefficient initiation of DDR (as measured by retarded γ-H2AX response) as well as inhibition of interaction between ATM, γ-H2AX, and MRN as part of the DDR complex. As a result, activated nuclear PKR retards DDR and leads to insufficient DSB repair as detected by prolonged Olive Tail Moment in a neutral Comet assay. However, since DNA repair can be restored by inhibiting PKR (by either knock-down or treatment with a PKR inhibitor), this supports a negative regulatory role for PKR in DDR and DSB repair Additional studies further demonstrate that PKR may block DDR by inhibiting ATM activity indirectly by binding with and activating PP2A, a known ATM protein phosphatase. Furthermore, in support of PKR inhibiting DSB repair, in vivo studies reveal that age-related or IR-induced genetic instability is more prevalent in PKR Tg vs WT mice and markedly lower in PKR knock-out mice as measured by the loss of GPI-linked CD24 on reticulocytes (a measure of increased somatic mutation rates due to loss of X-linked GPI activity). Interestingly, an increased somatic mutation rate and a more rapid evolution from MDS to acute leukemia is observed for double transgenic TgPKR/NHD13 vs Wt/NHD13 mice, which is significantly higher than evolution observed in PKRnull/NHD13 mice. Collectively, these data identify a novel function for PKR in suppressing DDR and DSB repair, which may enhance genetic instability and play a fundamental role in the evolution of MDS to acute leukemia. Citation Format: Xiaodong Cheng, Michael Byrne, Richard Lynn Bennett, Stratford William May. PKR promotes genetic instability and evolution of MDS to acute leukemia in mice by negatively regulating DDR and DNA repair in a novel mechanism. [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 LB-1. doi:10.1158/1538-7445.AM2014-LB-1
A skewed view of X chromosome inactivation
Authors: Jakub Minks, Wendy P. Robinson, Carolyn J. Brown
Journal: Journal of Clinical Investigation (2007)

X chromosome inactivation involves a random choice to silence either X chromosome early in mammalian female development. Once silenced the inactive X is stably inherited through subsequent somatic cell divisions, and thus, females are generally mosaics, having a mixture of cells with one or the other parental X active. While in most females the number of cells with either X being active is roughly equal, skewing of X chromosome inactivation is observed in a percentage of women. In this issue of the JCI, Bolduc and colleagues address whether skewing of X chromosome inactivation in humans is influenced by an X-linked locus that can alter this initial random inactivation (see the related article beginning on page 333). Their data indicate that most of the skewing observed in humans results from secondary events rather than being due to an inherited tendency to inactivate a particular X chromosome.
Sustained hepatitis C virus clearance and increased hepatitis B surface antigen seroclearance in patients with dual chronic hepatitis C and B during posttreatment follow-up
Authors: Ming-Lung Yu, Chuan-Mo Lee, Chi-Ling Chen, Wan-Long Chuang, Sheng-Nan Lu, Chen-Hua Liu, Shun-Sheng Wu, Li-Ying Liao, Hsing-Tao Kuo, You-Chen Chao, Shui-Yi Tung, Sien-Sing Yang, Jia-Horng Kao, Wei-Wen Su, Chih-Lin Lin, Hung-Chih Yang, Pei-Jer Chen, Ding-Shinn Chen, Chun-Jen Liu
Journal: Hepatology (2013)

Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared with monoinfected patients. Yet, there is a similar rate of sustained virologic response (SVR) after peginterferon alfa-2a and ribavirin combination therapy in these patients compared with HCV-monoinfected patients and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in coinfected patients was investigated in a 5-year follow-up study. Patients with active HCV genotype 1, both HBV-coinfected (n = 97) and HBV-monoinfected (n = 110), underwent 48-week combination therapy with peginterferon alfa-2a plus ribavirin. In patients with active HCV genotype 2 or 3, both HBV-coinfected (n = 64) and monoinfected (n = 50) patients underwent 24-week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks posttreatment follow-up; 264 (89.5%) patients agreed to receive additional follow-up for up to 5 years after the end of treatment. After a median follow-up of 4.6 ± 1.0 years, six of the 232 patients achieving SVR developed HCV RNA reappearance, including five HCV genotype 1/HBV-coinfected patients and one HCV genotype 2/3-monoinfected patient. Subgenomic analysis of the HCV core gene indicated that five patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI], 0.9%-5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI, 21.5%-42.0%); with 33.1% (95% CI, 21.8%-50.1%) in the 48-week combination therapy group and 24.3% (95% CI, 13.7%-42.9%) in the 24-week therapy group.Peginterferon alfa-2a and ribavirin therapy provides good HCV SVR durability and a high accumulative HBsAg seroclearance rate in patients who are coinfected with HCV and HBV. (HEPATOLOGY 2013;).
Effects of methylprednisolone on the ischemic damage in patients with acute myocardial infarction.
Authors: J E Madias, W B Hood
Journal: Circulation (1982)

In this double-blind randomized study, 19 patients with acute transmural myocardial infarction were treated with methylprednisolone administered 4.4 +/- 0.7 hours (+/- SEM) after the onset of chest pain, and were compared with 21 patients who received placebo 4.5 +/- 0.4 hours after the start of clinical symptoms. The two groups were comparable in reference to sex, prevalence of risk factors, clinical status on admission, location of myocardial infarction and magnitude of ischemic injury as assessed by standard ECGs and precordial ST-segment and QRS maps. The treated patients, however, were older than the patients who received placebo. Methylprednisolone in an i.v. dose of 2.0 g was administered on admission and a similar dose was infused 3 hours later. Placebo administration followed an identical schedule. Mortality, cardiac rupture, incidence of ventricular arrhythmias, blocks, extension of myocardial infarction, pericarditis, postinfarction chest pain, persistent ST-segment elevation at discharge, and change in Killip class during hospitalization were the same in both groups. Peak enzyme values, and changes in ECG variables pertaining to resolution of ST-segment elevation or development of QRS evolutionary alterations were similar in both groups. Follow-up for 6 months did not reveal any differences in the clinical course of the two groups. Methylprednisolone infused in a total dose of 4.0 g within 12 hours after the onset of chest pain in patients with acute transmural myocardial infarction does not result in any demonstrable beneficial or harmful effects.
Abstract 2554: Copper transporter 2 (CTR2) is able to transport cisplatin and/or oxaliplatin in drug-resistant cell lines
Authors: Edina M. Komlodi-Pasztor, Robert Murphy, Julia Wilkerson, Tito Fojo
Journal: Cancer Research (2010)

Abstract The clinical use of platinum (Pt) agents is often compromised by the occurrence of drug resistance. Studies have shown reduced intracellular Pt accumulation in cells resistant to Pt drugs. Copper transporters have been reported to have a role in Pt influx and efflux. While the first member of this family, CTR1, has been shown to transport Pt, the role of the structurally similar CTR2 in Pt transport is unclear. The aim of this study was to assess the role of CTR2 in Pt based drug-transport using KB-3.1 cervical carcinoma cells and its cisplatin (KB-CP20) or oxaliplatin (KB-OX60) resistant subclones. In previous studies we reported that compared to parental cells the resistant cell lines have lower levels of intracellular Pt following cisplatin (CIS) or oxaliplatin (OX) exposure. We transfected parental KB-3.1 cells and its drug resistant sublines with CTR1, CTR2 or both transporters, and incubated cells with either CIS or OX. Intracellular Pt accumulation was not increased in any of the transfected parental KB-3.1 cells. In contrast, KB-CP20 cells transfected with CTR1, CTR2 or both trasnporters accumulated more CIS but not more OX compared to non-transfected KB-CP20 cells; while transfected KB-OX60 cells accumulated higher levels of both CIS and OX compared to non-transfected KB-OX 60 cells. In both resistant cell lines, the increased intracellular Pt observed after transtfection of the transporters was accompanied by increased DNA platination. Given the clinical utility of OX in colon carcinoma we next determined intracellular CIS and OX levels, the expression of proteins involved in copper transport (ATP7A, ATP7B, CTR1 and CTR2), and the IC50 for CIS and OX of six colon carcinoma cell lines. We found an inverse correlation between intracellular Pt levels and the IC50 of both drugs, and correlations between: (1) the IC50 of CIS and expression levels of CTR1, (2) intracellular CIS levels and expression levels of ATP7A, (3) expression levels of ATP7B and CTR2, and (4) OX accumulation and expression levels of ATP7A. In summary, we have shown CTR2 is able to transport Pt-containing drugs and increases intracellular Pt accumulation that is accompanied by greater DNA-platination. In unselected colon cancer cells, we have shown that the IC50 of a Pt based drug is determined by the intracellular accumulation of that drug, and to varying extent by the expression of copper transporters. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2554.
Setting and Motivation in Brief Psychotherapy
Authors: E. Gilliéron
Journal: Psychotherapy and Psychosomatics (1987)

The author reminds first a few elements of his own conception about the focalization as well as the influence of the setting on the psychic functioning. He shows how the dynamic elements which enlighten the central conflict of the patient occur already during the first minutes of the first interview. Such a conceptualization applies not only to short psychotherapies but also to all vital experiences which may be solved with a punctual psychotherapeutic intervention (1–3 sessions).
Adverse life events and breast cancer: case-control study
Authors: C C Chen, A S David, H Nunnerley, M Michell, J L Dawson, H Berry, J Dobbs, T Fahy
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To investigate the strength of association between past life events and the development of breast cancer. <b>Design</b>: Case-control study. A standardised life events interview and rating was administered before a definitive diagnosis. <b>Setting</b>: Breast Cancer Screening Assessment Unit and surgical outpatient clinics at King9s College Hospital, London. <b>Subjects</b>: 119 consecutive women aged 20-70 who were referred for biopsy of a suspicious breast lesion. <b>Main outcome measures</b>: Odds ratio of the risk of developing breast cancer after life events in the preceding five years after adjustment for confounders. <b>Results</b>: 41 women were diagnosed as having malignant disease while the remainder had benign conditions. Severe life events increased the risk of breast cancer. The crude odds ratio was 3.2 (95% confidence interval 1.35 to 7.6). After adjustment for age and the menopause and other potential confounders this rose to 11.6 (3.1 to 43.7). Multiple logistic regression analysis showed that all severe events and coping with the stress of adverse events by confronting them and focusing on the problems significantly predicted a diagnosis of breast cancer. Non-severe life events and long term difficulties had no significant association. <b>Conclusion</b>: These findings suggest an aetiological association between life stress and breast cancer.