tbuckley/cabot-search huggingface dataset:
How do SSRIs help patients with irritable bowel syndrome?
Authors: F Creed
Journal: Gut (2005)

Selective serotonin reuptake inhibitor antidepressants seem to promote global well being in some patients with irritable bowel syndrome and, possibly, some improvement in abdominal pain and bowel symptoms, but this effect appears to be independent of improved depression

In the randomised controlled trial reported in this issue of Gut , Tack and colleagues1 compared citalopram and placebo in 23 patients with irritable bowel syndrome (IBS) over a six week initial treatment period using a parallel group design (see page 1095) . The dose of citalopram was similar to that used in the treatment of depressive disorders but any patients with depressive disorder were excluded from this trial. The results showed that citalopram was superior to placebo in terms of the primary outcome measure—days with abdominal pain—and this improvement was unrelated to change in mood, change in stool pattern, or the effect of intravenous citalopram on rectal distension thresholds.

Overall this was not a good trial. The total number of outcome measures exceeded the number of subjects in the trial. The crossover part of the trial was discounted because symptoms did not return to baseline values after the first treatment period. It is not at all clear how the patients were selected and, therefore, whether the results might be generalised to clinic populations. Strengths of the study however include the high participation rate throughout the trial and the combined diary and questionnaire measurements.

In spite of the weaknesses of the trial design, this report is interesting because of the paucity of randomised placebo controlled trials of selective serotonin reuptake inhibitor (SSRI) antidepressants in IBS.2,3 In one trial of patients who had failed to respond to a high fibre diet, Tabas et al found that a low dose of paroxetine was superior to placebo in terms of overall …
Cellular Signaling Underlying Atrial Tachycardia Remodeling of L-type Calcium Current
Authors: Xiao Yan Qi, Yung-Hsin Yeh, Ling Xiao, Brett Burstein, Ange Maguy, Denis Chartier, Louis R. Villeneuve, Bianca J.J.M. Brundel, Dobromir Dobrev, Stanley Nattel
Journal: Circulation Research (2008)

Atrial tachycardia (AT) downregulates L-type Ca(2+) current (I(CaL)) and causes atrial fibrillation-promoting electric remodeling. This study assessed potential underlying signal transduction. Cultured adult canine atrial cardiomyocytes were paced at 0, 1, or 3 Hz (P0, P1, P3) for up to 24 hours. Cellular tachypacing (P3) mimicked effects of in vivo AT: decreased I(CaL) and transient outward current (I(to)), unchanged I(CaT), I(Kr), and I(Ks), and reduced action potential duration (APD). I(CaL) was unchanged in P3 at 2 and 8 hours but decreased by 55+/-6% at 24 hours. Tachypacing caused Ca(2+)(i) accumulation in P3 cells at 2 to 8 hours, but, by 24 hours, Ca(2+)i returned to baseline. Ca(v)1.2 mRNA expression was not altered at 2 hours but decreased significantly at 8 and 24 hours (32+/-4% and 48+/-4%, respectively) and protein expression was decreased (47+/-8%) at 24 hours only. Suppressing Ca(2+)(i) increases during tachypacing with the I(CaL) blocker nimodipine or the Ca(2+) chelator BAPTA-AM prevented I(CaL) downregulation. Calcineurin activity increased in P3 at 2 and 8 hours, respectively, returning to baseline at 24 hours. Nuclear factor of activated T cells (NFAT) nuclear translocation was enhanced in P3 cells. Ca(2+)-dependent signaling was probed with inhibitors of Ca(2+)/calmodulin (W-7), calcineurin (FK-506), and NFAT (INCA6): each prevented I(CaL) downregulation. Significant APD reductions ( approximately 30%) at 24 hours in P3 cells were prevented by nimodipine, BAPTA-AM, W-7, or FK-506. Thus, rapid atrial cardiomyocyte activation causes Ca(2+) loading, which activates the Ca(2+)-dependent calmodulin-calcineurin-NFAT system to cause transcriptional downregulation of I(CaL), restoring Ca(2+)i to normal at the cost of APD reduction. These studies elucidate for the first time the molecular feedback mechanisms underlying arrhythmogenic AT remodeling.
Somatic hypermutation, clonal diversity and preferential expression of the VH 51p1/VL kv 325 immunoglobulin gene combination in HCV-associated immunocytomas
Authors: G. Pozzato, F. Zorat, M. Fanni, S. Baracetti, L. Mazzoran, C. Mazzaro, O.R. Burrone, D.G. Efremov
Journal: Journal of Hepatology (1998)
How Should Remission From Depression Be Defined? The Depressed Patient’s Perspective
Authors: Mark Zimmerman, Joseph B. McGlinchey, Michael A. Posternak, Michael Friedman, Naureen Attiullah, Daniela Boerescu
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: Although experts in the treatment of depression have suggested that achieving remission is the primary goal of treatment, questions remain about how remission should be defined. In antidepressant efficacy trials, remission is defined according to scores on symptom severity scales. Normalization of functioning is often mentioned as an important component of remission, although it is not used to identify patients with remission in treatment studies. The authors’ goal was to determine what depressed patients consider important in defining remission from depression. METHOD: A brief questionnaire was distributed to 535 psychiatric outpatients who were being treated for DSM-IV major depressive episode. They were asked to rate the importance of 16 statements in determining whether depression is in remission. RESULTS: The three items most frequently judged to be very important in determining remission were the presence of features of positive mental health such as optimism and self-confidence; a return to one’s usual, normal self; and a return to usual level of functioning. The patients endorsed a statement about absence of symptoms with nearly similar frequency. CONCLUSIONS: Patients aspire to a range of outcomes from the treatment of their depression.
Spontaneous Tumorigenesis in Mice Overexpressing the p53-Negative Regulator Mdm4
Authors: Shunbin Xiong, Vinod Pant, Young-Ah Suh, Carolyn S. Van Pelt, Yongxing Wang, Yasmine A. Valentin-Vega, Sean M. Post, Guillermina Lozano
Journal: Cancer Research (2010)

High levels of the critical p53 inhibitor Mdm4 is common in tumors that retain a wild-type p53 allele, suggesting that Mdm4 overexpression is an important mechanism for p53 inactivation during tumorigenesis. To test this hypothesis in vivo, we generated transgenic mice with widespread expression of Mdm4. Two independent lines of transgenic mice, Mdm4(Tg1) and Mdm4(Tg15), developed spontaneous tumors, the most prevalent of which were sarcomas. To determine whether overexpression of Mdm4 also cooperated with p53 heterozygosity to induce tumorigenesis, we generated Mdm4(Tg1) p53(+/-) mice. These mice had significantly accelerated tumorigenesis and a distinct tumor spectrum with more carcinomas and significantly fewer lymphomas than p53(+/-) or Mdm4(Tg1) mice. Importantly, the remaining wild-type p53 allele was retained in most Mdm4(Tg1) p53(+/-) tumors. Mdm4 is thus a bona fide oncogene in vivo and cooperates with p53 heterozygosity to drive tumorigenesis. These Mdm4 mice will be invaluable for in vivo drug studies of Mdm4 inhibitors.
Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.
Authors: C H Sung, C P Hu, H C Hsu, A K Ng, C K Chou, L P Ting, T S Su, S H Han, C M Chang
Journal: Journal of Clinical Investigation (1989)

Previous reports indicate that human hepatocytes do not express class I and class II MHC antigens. Our analyses on 10 human hepatocellular carcinoma (HCC) cell lines by immunofluorescence tests and RIA, demonstrate that all the human HCC cell lines tested express class I MHC antigens and among them, three poorly differentiated human HCC cell lines also express class II MHC antigens. Results of immunoprecipitation and/or Western blotting experiments indicate similarity in the chemical nature of both the class I and class II MHC antigens expressed by the human HCC cell lines and by a human B lymphoblastoid cell line Raji. Furthermore, a new variant form of class I antigen was detected in some of these HCC cell lines. Immunohistochemical studies of HCC tissues using the peroxidase-antiperoxidase staining method indicated that class I and class II antigens were detectable in 7 out of 11 and 3 out of 11 HCC tissues from patients, respectively. The availability of MHC class I antigen-positive cultured HCC cell lines, including the poorly differentiated lines that also express MHC class II antigen, has provided us with interesting models to study the relationship between expression of MHC antigen and transformation and differentiation of human hepatocytes. These studies will also allow us some insight into the role of MHC class I and class II antigen in the immunosensitivity and immunogenicity of HCC cells to the host-immune response.
PWE-161 The Macrogol Drink Test To Distinguish Functional Constipation (fc) And Constipation Predominant Irritable Bowel Syndrome (ibs-c): Underlying Mechanisms Demonstrated Using Mri: Abstract PWE-161 Table 1
Authors: C Lam, G Chaddock, C Hoad, C Costigan, E Cox, S Pritchard, K Garsed, L Marciani, P Gowland, R Spiller
Journal: Gut (2014)

<h3>Introduction</h3> Patients with constipation may have either FC or IBS-C which require different treatments. They are often dissatisfied with their treatment because diagnosis relies on symptoms which frequently overlap. <h3>Methods</h3> 46 CC patients (24 FC and 22 IBS-C), age 18–68 years, unresponsive to simple laxatives, were compared with 11 healthy volunteers (HV). Whole gut transit (WGT) was assessed using a MRI scan 24 h following ingestion of 5 marker pills as previously validated. Patients then consumed 1 litre of macrogol (MCG) followed by hourly MRI scans for 4 h and scored bowel symptoms from 0–10 (none-severe). Colonic movements were assessed using a motility index (MI) based on colonic wall movement and hypersensitivity index (HI) was calculated as bloating symptom/ascending colon (AC) volume. <h3>Results</h3> Mean (SD) See Table 1. FC and IBS-C have slower WGT and higher HI than HV. FC showed significantly greater fasting SBWC, AC volume and reduced MI following ingestion of MCG compared to HV and IBS-C. Moreover, FC showed impaired response to MCG with longer time to first bowel movement and reduced stool frequency on the study day when compared with HV and IBS-C. Time to 1st bowel movement correlated significantly with AC volume 2h post MCG, r = 0.44, p = 0.004 and fasting SBWC,r = 0.34,p = 0.035. Using a cut-off &gt;230 min distinguishes FC from IBS-C with sensitivity 55% and specificity 95%; this needs validation in a repeat study. <h3>Conclusion</h3> Time to first bowel movement &gt;230 min makes IBS unlikely and should help target treatments. Our MI studies show this is dueto greater motility response to distension in IBS-C who has lower fasting SBWC and AC volumes versus FC. IBS-C showed similar features to HV but can be distinguished by greater HI following distension which suggest hypersensitivity. This inexpensive test done without MRI could help clinicians to distinguish these 2 conditions. <h3>Disclosure of Interest</h3> C. Lam: None Declared, G. Chaddock: None Declared, C. Hoad: None Declared, C. Costigan: None Declared, E. Cox: None Declared, S. Pritchard: None Declared, K. Garsed: None Declared, L. Marciani: None Declared, P. Gowland Consultant for: Merck, Ironwood, Unilever, R. Spiller Grant/research support from: Lessaffre, Ironwood, Consultant for: Almirall, Astellas, Danone and Sanofi, Conflict with: Free drug for clinical trial from Norgine.
Targeted Deletion of Fgl-2/Fibroleukin in the Donor Modulates Immunologic Response and Acute Vascular Rejection in Cardiac Xenografts
Authors: Michael Mendicino, MingFeng Liu, Anand Ghanekar, Wei He, Cheryl Koscik, Itay Shalev, Mojib Javadi, Julie Turnbull, Wenhao Chen, Laisum Fung, Seisuke Sakamoto, Phillip Marsden, Thomas K. Waddell, M. James Phillips, Reginald Gorczynski, Gary A. Levy, David Grant
Journal: Circulation (2005)

Xenografts ultimately fail as a result of acute vascular rejection (AVR), a process characterized by intravascular thrombosis, fibrin deposition, and endothelial cell activation.We studied whether targeted deletion of Fgl-2, an inducible endothelial cell procoagulant, (Fgl-2-/-) in the donor prevents AVR in a mouse-to-rat cardiac xenotransplantation model. By 3 days after transplant, Fgl-2+/+ grafts developed typical features of AVR associated with increased levels of donor Fgl-2 mRNA. Grafts from Fgl-2-/- mice had reduced fibrin deposition but developed cellular rejection. Treatment with a short course of cobra venom factor and maintenance cyclosporine resulted in long-term acceptance of both Fgl-2+/+ and Fgl-2-/- grafts. On withdrawal of cyclosporine, Fgl-2+/+ grafts developed features of AVR; in contrast, Fgl-2-/- grafts again developed acute cellular rejection. Rejecting Fgl-2+/+ hearts stained positively for IgG, IgM, C3, and C5b-9, whereas rejecting Fgl-2-/- hearts had minimal Ig and complement deposition despite xenoantibodies in the serum. Furthermore, serum containing xenoantibodies failed to stain Fgl-2-/- long-term treated hearts but did stain wild-type heart tissues. Treatment of Fgl-2-/- xenografts with mycophenolate mofetil and tacrolimus, a clinically relevant immune suppression protocol, led to long-term graft acceptance.Deletion of Fgl-2 ameliorates AVR by downregulation of xenoantigens and may facilitate successful clinical heart xenotransplantation.
Bilateral and Unilateral ECT: Follow-Up Study and Critique
Authors: T. G. BIDDER, J. J. STRAIN, L. BRUNSCHWIG
Journal: American Journal of Psychiatry (1970)

The authors conclude from their work and from a critical review of the literature that unilateral ECT is likely to result in reduced memory dysfunction during the immediate treatment period and to require more treatment sessions for satisfactory immediate therapeutic response. In the patient who is a guarded risk, attainment of a transiently reduced memory loss with a method likely to require additional anesthetic exposure (more treatments) would appear to be unwarranted. The authors stress the need for further studies using careful methodological design and techniques.
Clinical implication of centrosome amplification in plasma cell neoplasm
Authors: Wee J. Chng, Greg J. Ahmann, Kim Henderson, Rafael Santana-Davila, Philip R. Greipp, Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri, Shaji Kumar, S. Vincent Rajkumar, John A. Lust, Robert A. Kyle, Steven R. Zeldenrust, Suzanne R. Hayman, Rafael Fonseca
Journal: Blood (2005)
Pharmacologic Repression of Retinoic Acid Receptor–Related Orphan Nuclear Receptor γ Is Therapeutic in the Collagen‐Induced Arthritis Experimental Model
Authors: Mi Ra Chang, Brent Lyda, Theodore M. Kamenecka, Patrick R. Griffin
Journal: Arthritis & Rheumatology (2013)

The nuclear receptor retinoic acid receptor-related orphan nuclear receptor γ (RORγ; T cell-specific isoform RORγt) is a key regulator of Th17 cell differentiation, controlling the production of the inflammatory cytokine interleukin-17 (IL-17). Lipopolysaccharide (LPS) stimulation of monocytes leads to the induction of RORγ. We previously showed that the potent and selective inverse agonist of RORγ, SR2211, was effective at suppressing IL-17 production in EL4 cells. The aim of this study was to examine the effects of SR2211 treatment on proinflammatory cytokine expression in LPS-stimulated RAW 264.7 cells as well as on joint inflammation in vivo in mice with collagen-induced arthritis (CIA).Collagen was injected into the tail of DBA mice, followed by a booster inoculation 21 days later. Three days prior to the booster inoculation, SR2211 was administered twice daily for 15 days. Thymus, spleen, and draining lymph nodes (DLNs) were then harvested, and Th17 cell differentiation and DLN stimulation were performed.Treatment of Th17 cells with SR2211 suppressed the expression and production of inflammatory cytokines. Likewise, SR2211 reduced inflammatory cytokine production in LPS-stimulated RAW 264.7 cells. Mice with CIA that received SR2211 twice daily for 15 days exhibited a statistically significant reduction in joint inflammation as compared to mice that received only vehicle. Interestingly, systemic Th1 cell activation was detected in SR2211-treated mice with CIA, as indicated by an increase in interferon-γ levels.The findings of this study support the idea of targeting RORγ to therapeutically repress inflammatory T cell function and macrophage activation in humans with rheumatoid arthritis. Compounds such as SR2211 have potential utility for the treatment of inflammatory disease.
Sex and Racial Differences in the Use of Implantable Cardioverter-Defibrillators Among Patients Hospitalized With Heart Failure
Authors: Adrian F. Hernandez, Gregg C. Fonarow, Li Liang, Sana M. Al-Khatib, Lesley H. Curtis, Kenneth A. LaBresh, Clyde W. Yancy, Nancy M. Albert, Eric D. Peterson
Journal: JAMA (2007)

Practice guidelines recommend implantable cardioverter-defibrillator (ICD) therapy for patients with heart failure and left ventricular ejection fraction of 30% or less. The influence of sex and race on ICD use among eligible patients is unknown.
Expression and modulation of apoptosis regulatory molecules in human melanocytes: significance in vitiligo
Authors: R.M.J.G.J. Van Den Wijngaard, J. Aten, A. Scheepmaker, I.C. Le Poole, A.J. Tigges, W. Westerhof, P.K. Das
Journal: British Journal of Dermatology (2000)

Although the aetiology of the hypopigmentary disorder vitiligo is ill understood, it is clear that pigment producing cells are absent from vitiliginous lesional skin. The present study was designed to investigate the possible role of melanocyte-expressed apoptosis regulatory molecules in melanocyte disappearance. Flow cytometric evaluation of p53, p21, Bcl-2 and Bax revealed no differences in in vitro expression levels between normal control and non-lesional melanocytes. Moreover, no in situ immunohistological differences were observed in melanocytes present in control, non-lesional and perilesional skin. However, an enhanced number of p53+ nuclei, in the absence of detectable p21 expression, was detected in involved areas. The observed p53 expression pattern did not involve melanocytes and could be the result of ultraviolet (UV) A irradiation. Further, we showed that UVB is capable of modulating melanocyte-expressed apoptosis regulatory molecules. Consequently, a lethal dose of UVB was given to two groups of cultured normal control and non-lesional melanocytes. No significant differences were found when comparing the percentages and kinetics of UVB-induced apoptosis in these groups. In conclusion, our results indicate that the relative apoptosis susceptibility of melanocytes in vitiligo is comparable with that of normal control cells. It is therefore unlikely that vitiligo is causally related to dysregulation of apoptosis regulatory molecules.
A Prospective Study of Obesity and Risk of Coronary Heart Disease Among Diabetic Women
Authors: Eunyoung Cho, Joann E. Manson, Meir J. Stampfer, Caren G. Solomon, Graham A. Colditz, Frank E. Speizer, Walter C. Willett, Frank B. Hu
Journal: Diabetes Care (2002)

OBJECTIVE—To examine the relationship of obesity, measured as BMI, and weight change to incidence of coronary heart disease (CHD) among women with diabetes. RESEARCH DESIGN AND METHODS—We followed 5,897 women with type 2 diabetes in the Nurses’ Health Study for ≤20 years. Women were aged 40–74 years and had no history of cardiovascular disease or cancer at the beginning of the follow-up period. BMI values from three time points (age 18 years, year 1976, and current) were derived from the reported height (1976) and corresponding reported weight. Weight changes between age 18 years and 1976 and after diagnosis of diabetes were calculated. Women reported diagnoses of diabetes and CHD every 2 years. Incident CHD cases were confirmed by medical record review. RESULTS—During follow-up, we documented 418 incident cases of CHD (236 of nonfatal myocardial infarction and 182 of fatal CHD). After adjustment for age, smoking, and other coronary risk factors, current BMI was strongly associated with increased risk of CHD among diabetic women. The multivariate relative risks across increasing categories of BMI (&amp;lt;23.0, 23.0–24.9, 25.0–26.9, 27.0–29.9, 30.0–34.9, and ≥35.0 kg/m2) were 1.0, 1.58, 1.85, 1.95, 2.80, and 3.21, respectively (P for trend &amp;lt;0.001). Increasing BMI values from age 18 years to 1976, before diagnosis of diabetes, were also positively associated with risk of CHD. Weight gain before the diagnosis of diabetes was related to increased risk of CHD. In contrast, weight change after diagnosis of diabetes was not associated with risk of CHD. CONCLUSIONS—These findings provide strong evidence that obesity and weight gain before diagnosis of diabetes are associated with future risk of CHD among women with type 2 diabetes.
The Field of Radiation Therapy May Effect Health-Related Quality of Life in Patients With Operable Breast Cancer
Authors: Muzaffer Altundag, Kadri Altundag, Mustafa Cengiz, Ozden Altundag
Journal: Journal of Clinical Oncology (2004)

TO THE EDITOR: We read with great interest the article by Brandberg et al concerning the effects on healthrelated quality of life of two adjuvant anthracyclinecontaining treatments in high-risk breast cancer patients. They observed that higher levels of problems in arm symptoms were reported in the tailored fluorouracil, epirubicin, and cyclophosphamide group, compared with the high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin group. In this study, locoregional radiotherapy was given daily in 2-Gy fractions five times per week to a total dose of at least 46 Gy. But details of radiotherapy that may affect the physical function and symptoms related to arm edema in both treatment groups were not mentioned. Whether or not the patients received lymphatic irradiation, particularly internal mammary irradiation, is important because internal mammary irradiation, and in some cases, tangential radiation to breast, may add to the cardiotoxicity caused by anthracycline, which may in turn affect physical function. On the other hand, axillary and supraclavicular radiation clearly increases the risk of lymphedema in the upper extremity, which is important for functional outcome.
Creatinine Phosphokinase Levels in Hypothyroidism
Authors: Dhanwada S. Rao, Boy Frame
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The recent article by Goldman et al (238:325, 1977) on high elevations of creatinine phosphokinase (CPK) levels in hypothyroidism interested us very much. We have encountered two such patients (64-year-old and 60-year-old women) who became hypothyroid following radioactive iodine therapy for Grave's disease. On initial screening both were hypothyroid clinically and biochemically. Serum thyroxine levels were 0.2 μg/dl and 1.2 μg/dl (normal 5 to 11 μg/dl). Serum thyroid stimulating hormone level by radioimmunoassay was &gt;100 μU—l and 50 μU/ml, respectively. In addition, both of them had very high CPK levels (&gt; 2,000 mU/ml and 978 mU/ml, respectively; normal, &lt;190 mU/ml). In one patient it consisted exclusively of MM isoenzyme fractions. Concurrent elevations of lactic dehydrogenase and transaminase levels were also noted. All these abnormalities returned to normal in two or three weeks following replacement therapy. These two patients add to the observation of Goldman et al with
Prognostic Factors for Survival and Sequencing of Life-Extending Therapies in Metastatic Castration Resistant Prostate Cancer (Mcrpc) Patients (Pts) in Post-Docetaxel (D) Setting
Authors: S. Oudard, A. Angelergues, I. Gonzalez Maeso, N. Delanoy, A. Flechon, M. Özgüroğlu, D.E. Castellano, A. Guillot, S. Le Moulec, E. Esteban, J. Munarriz, B. Campos, J. Bellmunt
Journal: Annals of Oncology (2014)