tbuckley/cabot-search huggingface dataset:
Randomised controlled trial of clinical medication review by a pharmacist of elderly patients receiving repeat prescriptions in general practice
Authors: A. G Zermansky, D. R Petty, D. K Raynor, N. Freemantle, A. Vail, C. J Lowe
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine whether a pharmacist can effectively review repeat prescriptions through consultations with elderly patients in general practice. <b>Design:</b> Randomised controlled trial of clinical medication review by a pharmacist against normal general practice review. <b>Setting:</b> Four general practices. <b>Participants:</b> 1188 patients aged 65 or over who were receiving at least one repeat prescription and living in the community. <b>Intervention:</b> Patients were invited to a consultation at which the pharmacist reviewed their medical conditions and current treatment. <b>Main outcome measures:</b> Number of changes to repeat prescriptions over one year, drug costs, and use of healthcare services. <b>Results:</b> 590 (97%) patients in the intervention group were reviewed compared with 233 (44%) in the control group. Patients seen by the pharmacist were more likely to have changes made to their repeat prescriptions (mean number of changes per patient 2.2 <i>v</i> 1.9; difference=0.31, 95% confidence interval 0.06 to 0.57; P=0.02). Monthly drug costs rose in both groups over the year, but the rise was less in the intervention group (mean difference £4.72 per 28 days, −£7.04 to -£2.41); equivalent to £61 per patient a year. Intervention patients had a smaller rise in the number of drugs prescribed (0.2 <i>v</i> 0.4; mean difference −0.2, −0.4 to −0.1). There was no evidence that review of treatment by the pharmacist affected practice consultation rates, outpatient consultations, hospital admissions, or death rate. <b>Conclusions:</b> A clinical pharmacist can conduct effective consultations with elderly patients in general practice to review their drugs. Such review results in significant changes in patients9 drugs and saves more than the cost of the intervention without affecting the workload of general practitioners. <h3>What is already known on this topic</h3> Review of patients on long term drug treatment is important but is done inadequately Evidence from the United States shows that pharmacists can improve patient care by reviewing drug treatment <h3>What this study adds</h3> Consultations with a clinical pharmacist are an effective method of reviewing the drug treatment of older patients Review by a pharmacist results in more drug changes and lower prescribing costs than normal care plus a much higher review rate Use of healthcare services by patients is not increased
Proline Metabolism and Microenvironmental Stress
Authors: James M. Phang, Wei Liu, Olga Zabirnyk
Journal: Annual Review of Nutrition (2010)

Proline, the only proteinogenic secondary amino acid, is metabolized by its own family of enzymes responding to metabolic stress and participating in metabolic signaling. Collagen in extracellular matrix, connective tissue, and bone is an abundant reservoir for proline. Matrix metalloproteinases degrading collagen are activated during stress to make proline available, and proline oxidase, the first enzyme in proline degradation, is induced by p53, peroxisome proliferator-activated receptor γ (PPARγ) and its ligands, and by AMP-activated protein kinase downregulating mTOR. Metabolism of proline generates electrons to produce ROS and initiates a variety of downstream effects, including blockade of the cell cycle, autophagy, and apoptosis. The electrons can also enter the electron transport chain to produce adenosine triphosphate for survival under nutrient stress. Pyrroline-5-carboxylate, the product of proline oxidation, is recycled back to proline with redox transfers or is sequentially converted to glutamate and alpha-ketoglutarate. The latter augments the prolyl hydroxylation of hypoxia-inducible factor-1α and its proteasomal degradation. These effects of proline oxidase, as well as its decreased levels in tumors, support its role as a tumor suppressor. The mechanism for its decrease is mediated by a specific microRNA. The metabolic signaling by proline oxidase between oxidized low-density lipoproteins and autophagy provides a functional link between obesity and increased cancer risk.
Combining Betulinic Acid and Mithramycin A Effectively Suppresses Pancreatic Cancer by Inhibiting Proliferation, Invasion, and Angiogenesis
Authors: Yong Gao, Zhiliang Jia, Xiangyu Kong, Qiang Li, David Z. Chang, Daoyan Wei, Xiangdong Le, Huang Suyun, Shengdong Huang, Liwei Wang, Keping Xie
Journal: Cancer Research (2011)

Abstract Both betulinic acid (BA) and mithramycin A (MIT) exhibit potent antitumor activity through distinct mechanisms of Sp1 inhibition. However, it is unknown whether a combination of these two compounds results in a synergistic inhibitory effect on pancreatic cancer growth and/or has a therapeutic advantage over gemcitabine. In xenograft mouse models of human pancreatic cancer, treatment with either BA or MIT alone showed dose-dependent antitumor activity but led to systemic side effects as measured by overall weight loss. Treatment with a nontoxic dose of either compound alone had only marginal antitumor effects. Importantly, combination treatment with nontoxic doses of BA and MIT produced synergistic antitumor activity, including inhibitory effects on cell proliferation, invasion, and angiogenesis. The treatment combination also produced less discernible side effects than therapeutic doses of gemcitabine. Moreover, combined treatment of BA and MIT resulted in drastic inhibition of Sp1 recruitment onto Sp1 and VEGF promoters, leading to transcriptional inhibition of both Sp1 and VEGF and downregulation of Sp1 and VEGF protein expression. Ectopic overexpression of Sp1 rendered tumor cells resistant to BA, MIT, and the combination of the two. Overall, our findings argue that Sp1 is an important target of BA and MIT and that their combination can produce an enhanced therapeutic response in human pancreatic cancer. Cancer Res; 71(15); 5182–93. ©2011 AACR.
Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2
Authors: Olivier Morteau, Scott G. Morham, Rance Sellon, Levinus A. Dieleman, Robert Langenbach, Oliver Smithies, R. Balfour Sartor
Journal: Journal of Clinical Investigation (2000)

To investigate roles in intestinal inflammation for the 2 cyclooxygenase (COX) isoforms, we determined susceptibility to spontaneous and induced acute colitis in mice lacking either the COX-1 or COX-2 isoform. We treated wild-type, COX-1–/–, COX-2–/–, and heterozygous mice with dextran sodium sulfate (DSS) to provoke acute colonic inflammation, and we quantified tissue damage, prostaglandin (PG) E2, and interleukin-1β. No spontaneous gastrointestinal inflammation was detected in mice homozygous for either mutation, despite almost undetectable basal intestinal PGE2 production in COX-1–/– mice. Both COX-1–/– and COX-2–/– mice showed increased susceptibility to a low-dose of DSS that caused mild colonic epithelial injury in wild-type mice. COX-2–/– mice were more susceptible than COX-1–/– mice, and selective pharmacologic blockade of COX-2 potentiated injury in COX-1–/– mice. At a high dose, DSS treatment was fatal to 50% of the animals in each mutant group, but all wild-type mice survived. DSS treatment increased PGE2 intestinal secretion in all groups except COX-2–/– mice. These results demonstrate that COX-1 and COX-2 share a crucial role in the defense of the intestinal mucosa (with inducible COX-2 being perhaps more active during inflammation) and that neither isoform is essential in maintaining mucosal homeostasis in the absence of injurious stimuli.
The Association Between Conventional Risk Factors and Diabetes Is Weak Among Urban Tanzanians
Authors: Daniel Faurholt-Jepsen, Nyagosya Range, George PrayGod, Kidola Jeremiah, Maria Faurholt-Jepsen, Martine Grosos Aabye, John Changalucha, Christian Ritz, Dirk Lund Christensen, Marit Eika Jørgensen, Åse Bengård Andersen, Henrik Friis
Journal: Diabetes Care (2013)

Sub-Saharan Africa is experiencing the highest relative increase in diabetes (1), but data are scarce, with only nine countries reporting prevalence surveys within the last decade (2). While biological and behavioral risk factors for diabetes are fairly well-described in high-income settings, it is not known to what extent such risk factors contribute to the diabetes epidemic in low-resource settings. The aim of the current study was to assess whether conventional Western population risk factors for diabetes are appropriate in identifying individuals with diabetes among urban Tanzanians.

The study took place in the urban setting of Mwanza City, which is located in northwestern Tanzania. The current study was part of a larger nutrition study (2006–2009) (3), and 743 healthy control subjects chosen from among tuberculosis patients were invited to participate. Individuals ≥15 years of age, nonpregnant, and without severe diseases were invited to participate. Ethical permission was obtained from the Medical Research Coordinating Committee of the National Institute for Medical Research, Tanzania. Standardized questionnaires were used to collect …
Idiotypes on major histocompatibility complex-restricted virus-immune cytotoxic T lymphocytes.
Authors: U R Kees
Journal: The Journal of Experimental Medicine (1981)

Specificity-associated determinants could be demonstrated on major histocompatibility complex (MHC)-restricted virus-immune cytotoxic T lymphocytes (CTL) using antisera raised in syngeneic mice. This result indicates that the number of clonotypes sufficiently small to allow the detection of such idiotypic determinants. The functional properties of three anti-idiotypic antisera were tested in blocking studies and by idiotypic antisera plus complement. Whereas the former test did not reveal any results obtained from binding studies, i.e., all three anti-idiotypic antisera specifically reacted with CTL of the type used for immunization and had no effect on syngeneic influenza-immune CTL, syngeneic alloreactive CTL, or NDV-immune CTL of an H-2-disparate strain. These results are discussed in terms of current models for MHC-restricted CTL responses.
Evaluation of fractional exhaled nitric oxide and peripheral blood eosinophil count as biomarkers in patients with refractory asthma
Authors: Adeel Sahal, Joyutpal Das, Adel Mansur
Journal: European Respiratory Journal (2013)

Introduction:  The role of fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophil (PBE) counts as biomarkers in refractory asthma is not well established. The aim of the study was to determine if there is a correlation between the two biomarkers in this population and to assess their relationship with a number of measures of asthma control.  Methods:  We retrospectively analysed the data of 102 patients with refractory asthma presenting to the Severe Asthma Unit at Birmingham Heartlands Hospital and analysed above mentioned correlation using Spearman9s rank correlation coefficient (Rs).  Results:  The mean AQLQ and ACQ were 3.27 and 3.54 respectively suggesting poor asthma control and quality of life in refractory asthma patients.  Patient on maintenance oral steroids had poorer quality of life compared to the patients not on maintenance oral steroids (mean AQLQ 2.91 vs.3.56, p=0.011). Similarly, asthma control was worse in patients on maintenance steroids (mean ACQ 3.63 vs. 3.43, p=0.36).  There was positive correlation between FENO and PBE (RS= 0.42, p = 0.01) but no significant correlation was found between AQLQ&ACQ and these biomarkers.  Subgroup analysis showed positive correlation between AQLQ and FENO in atopic group (RS= 0.338, p=0.03). Interestingly a weak negative correlation was seen between AQLQ and FENO in non- atopic group (RS= -0.38, p=0.075, n=22).  Conclusions:  Patients on maintenance oral steroids have poorer quality of life and asthma control. There is a positive correlation between FENO and PBE in refractory asthma patients but no significant correlation was found between AQLQ&ACQ and these biomarkers.
Genomic Loss of<i>miR-486</i>Regulates Tumor Progression and the<i>OLFM4</i>Antiapoptotic Factor in Gastric Cancer
Authors: Hue-Kian Oh, Angie Lay-Keng Tan, Kakoli Das, Chia-Huey Ooi, Nian-Tao Deng, Iain BeeHuat Tan, Emmanuel Beillard, Julian Lee, Kalpana Ramnarayanan, Sun-Young Rha, Nallasivam Palanisamy, P. Mathijs Voorhoeve, Patrick Tan
Journal: Clinical Cancer Research (2011)

MicroRNAs (miRNA) play pivotal oncogenic and tumor-suppressor roles in several human cancers. We sought to discover novel tumor-suppressor miRNAs in gastric cancer (GC).Using Agilent miRNA microarrays, we compared miRNA expression profiles of 40 primary gastric tumors and 40 gastric normal tissues, identifying miRNAs significantly downregulated in gastric tumors.Among the top 80 miRNAs differentially expressed between gastric tumors and normals (false discovery rate < 0.01), we identified hsa-miR-486 (miR-486) as a significantly downregulated miRNA in primary GCs and GC cell lines. Restoration of miR-486 expression in GC cell lines (YCC3, SCH and AGS) caused suppression of several pro-oncogenic traits, whereas conversely inhibiting miR-486 expression in YCC6 GC cells enhanced cellular proliferation. Array-CGH analysis of 106 primary GCs revealed genomic loss of the miR-486 locus in approximately 25% to 30% of GCs, including two tumors with focal genomic losses specifically deleting miR-486, consistent with miR-486 playing a tumor-suppressive role. Bioinformatic analysis identified the secreted antiapoptotic glycoprotein OLFM4 as a potential miR-486 target. Restoring miR-486 expression in GC cells decreased endogenous OLFM4 transcript and protein levels, and also inhibited expression of luciferase reporters containing an OLFM4 3' untranslated region with predicted miR-486 binding sites. Supporting the biological relevance of OLFM4 as a miR-486 target, proliferation in GC cells was also significantly reduced by OLFM4 silencing.miR-486 may function as a novel tumor-suppressor miRNA in GC. Its antioncogenic activity may involve the direct targeting and inhibition of OLFM4.
Detecting Bladder Cancer in the Chinese by Microsatellite Analysis: Ethnic and Etiologic Considerations
Authors: J. Zhang, Z. Fan, Y. Gao, Z. Xiao, C. Li, Q. An, S. Cheng
Journal: JNCI Journal of the National Cancer Institute (2001)

Microsatellite analysis of urine sediments has shown promise as a highly sensitive and specific technique for the detection of bladder cancer. However, most studies have been conducted in Western countries with Caucasian subjects. We explored the potential of microsatellite analysis for detecting bladder cancer in Chinese people.We performed microsatellite analysis of surgical specimens and urine sediment cells collected from Chinese patients with bladder tumors. Those microsatellite markers giving clearly readable patterns and showing susceptibility to alterations were used as a panel to detect primary tumors. A blinded study of additional patients with bladder cancer was performed to investigate the practical value of this panel for detecting bladder cancer. All statistical tests were two-sided.Thirty-eight bladder tumors and corresponding urine sediment specimens were initially screened for 60 microsatellite markers from 18 chromosomes. Nine markers, most of which were different from those that had been used for Western patients, with frequent alterations in the initial patients were selected for further analysis. In the subsequent blinded experiment, microsatellite alterations were observed in urine sediments from 22 (96%) of 23 patients with bladder cancer and from all three patients with inverted papilloma. None of the urine sediments from the one patient with bladder lipoma, from the one patient with neurofibroma, or from the 12 individuals without evidence of bladder tumor showed any microsatellite alterations.Microsatellite analysis of urine sediments could be a practical method for detecting bladder cancer in the Chinese. Our identification of different microsatellite markers highlights possible ethnic and etiologic disparities between the Chinese and Western bladder cancer patients.
Immunosuppressive activity in patients with active chronic hepatitis and primary biliary cirrhosis treated with azathioprine
Authors: G. Whelan, S. Sherlock
Journal: Gut (1972)

The rosette inhibition test was used to measure serum immunosuppressive activity after azathioprine (1·5 mg/kg) in 20 patients with liver disease (10 with active chronic hepatitis, six with primary biliary cirrhosis, and four with miscellaneous hepatic disorders) and in nine healthy normal volunteers. Where possible testing was repeated after one week and after at least two months of treatment. The titre of immunosuppression was related to the degree of impairment of hepatic function, and was found to be low in those with severe and normal in those with mild disturbance of hepatic function. Titres were unrelated to the presence of immunological abnormalities such as smooth muscle antibodies. In patients treated for at least two months there was no relationship between the initial titre of immunosuppressive activity and the response to treatment. Thus some patients improved despite failure to develop immunosuppressive activity, while others deteriorated even though immunosuppressive activity was normal when first studied. The development of immunosuppressive activity after azathioprine seems to be dependent on adequate hepatic function and the favourable response of some patients with liver disease to the drug may not be due entirely to immunosuppression.
A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck
Authors: T.Y. Seiwert, J. Fayette, D. Cupissol, J.M. del Campo, P.M. Clement, R. Hitt, M. Degardin, W. Zhang, A. Blackman, E. Ehrnrooth, E.E.W. Cohen
Journal: Annals of Oncology (2014)

BackgroundAfatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.Patients and methodsAn open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m2/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR).ResultsA total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade ≥3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab.ConclusionAfatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance.
The Concentration Dependence of Active Potassium Transport in the Human Red Blood Cell*
Authors: John R. Sachs, Louis G. Welt
Journal: Journal of Clinical Investigation (1967)

The relation between the active potassium influx in the human red blood cell and the extracellular potassium concentration does not appear to be consistent with the Michaelis-Menten model, but is adequately described by a model in which two potassium ions are required simultaneously at some site or sites in the transport mechanism before transport occurs. The same type of relation appears to exist between that portion of the sodium outflux that requires the presence of extracellular potassium and the extracellular potassium concentration. Rubidium, cesium, and lithium, which are apparently transported by the same system that transports potassium, stimulate the potassium influx when both potassium and the second ion are present at low concentrations, as is predicted by the two-site model.
Primary cutaneous marginal zone B-cell lymphoma: Response to treatment and disease-free survival in a series of 137 patients
Authors: Octavio Servitje, Cristina Muniesa, Yolanda Benavente, Verónica Monsálvez, M. Pilar Garcia-Muret, Fernando Gallardo, Eva Domingo-Domenech, Anna Lucas, Fina Climent, Jose L. Rodriguez-Peralto, Pablo L. Ortiz-Romero, Juan Sandoval, Ramon M. Pujol, M. Teresa Estrach
Journal: Journal of the American Academy of Dermatology (2013)
Prospective randomised multi-centre trial comparing the clinical efficacy, safety and patient acceptability of circular stapled anopexy with closed diathermy haemorrhoidectomy
Authors: M A Thaha, K L Campbell, S A Kazmi, L A Irvine, A Khalil, N R Binnie, W S Hendry, A Walker, H J Staines, R J C Steele
Journal: Gut (2008)

<h3>Objective:</h3> Unlike excisional haemorrhoidectomy, stapled anopexy (SA), which does not involve radical excision, has theoretical advantages, thus offering potential patient benefits. We compared the clinical efficacy, safety and patient acceptability of SA, with closed haemorrhoidectomy (CH). <h3>Patients and methods:</h3> 182 patients with symptomatic haemorrhoids (grades II, III, IV) were randomly assigned to receive SA or CH and were followed for up to 1 year (6, 12, 24, 48 weeks) after operation. Postoperative pain, symptom control, complications, re-treatment rates, patient satisfaction, and quality of life were compared on an intention-to-treat basis. <h3>Results:</h3> Postoperative pain in the SA group (n = 91) was significantly lower (p = 0.004, Mann–Whitney U test). At 1 year there were no significant differences in the symptom load, symptom severity or the disease severity between the two groups. Overall complication rates were similar but faecal urgency was reported more frequently following SA (p = 0.093, Fisher's exact test). Despite a similar rate of residual symptoms, prolapse control was better with CH (p = 0.087, Fisher's exact test), and more patients in the SA group required re-treatment for residual prolapse at 1 year (p = 0.037, Fisher's exact test). However, more patients rated SA as an excellent operation at 6 and 12 weeks (p = 0.008 and 0.033, binary logistic regression) and were willing to undergo a repeat procedure if required (p = 0.018, Fisher's exact test). <h3>Conclusion:</h3> Stapled anopexy offers a significantly less painful alternative to excisional haemorrhoidectomy and achieves a higher patient acceptability. Although the overall symptom control and safety are similar in the majority of the patients, the re-treatment rate for recurrent prolapse at 1 year is higher following SA when compared to CH.