tbuckley/cabot-search huggingface dataset:
Microphthalmia transcription factor as a molecular marker for circulating tumor cell detection in blood of melanoma patients.
Authors: Kazuo Koyanagi, Steven J O'Day, Rene Gonzalez, Karl Lewis, William A Robinson, Thomas T Amatruda, Christine Kuo, He-Jing Wang, Robert Milford, Donald L Morton, Dave S B Hoon
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Microphthalmia transcription factor (Mitf), which is important in melanocyte development and melanoma growth, was assessed using real-time quantitative reverse transcription-PCR assay to investigate its expression as a marker for circulating melanoma cells in blood and determine the correlation with disease stage and survival in melanoma patients. EXPERIMENTAL DESIGN: In optimization studies for Mitf, we tested 15 melanoma cell lines, 41 peripheral blood lymphocytes from healthy volunteers, and 21 metastatic melanoma tissues. Blood specimens were procured from 90 patients with stage I (n = 20), stage II (n = 20), stage III (n = 28), and stage IV (n = 22) melanoma. Blood specimens were also obtained at four bleed intervals from 58 patients enrolled in a prospective multicenter trial of biochemotherapy before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. RESULTS: Under the optimized conditions, Mitf was negative in healthy peripheral blood lymphocytes and positive in all melanoma cell lines and 18 (86%) melanoma tissues. In the 90 patients, the rate of Mitf detection was higher with increasing American Joint Committee on Cancer stage (P &amp;lt; 0.0001). In the 58 patients treated with biochemotherapy and surgery, Mitf detection decreased with treatment (P = 0.019). Mitf detection after treatment was associated with a significantly lower relapse-free (P &amp;lt; 0.0001) and overall (P = 0.001) survival and was a significant independent prognostic factor for relapse-free (risk ratio, 5.63; P = 0.0004) and overall (risk ratio, 5.36; P = 0.005) survival. CONCLUSIONS: Mitf detection in blood can indicate subclinical metastatic disease and predict treatment outcome in melanoma patients.
New developments in the treatment of hepatitis C
Authors: S J Rossi
Journal: Gut (2003)

Treatment of chronic hepatitis C virus (HCV) infection with interferon based therapies has been part of clinical practice for more than 10 years. While there have been incremental steps in improving sustained virological response (SVR), limited progress has been made in developing agents that eradicate the virus in all infected patients.1 The development of effective antiviral agents has been hindered by several key factors, including the genetic heterogeneity of HCV, lack of available culture systems or animal models, limited understanding of the mechanisms of action of current therapies, and the long delay between initiation of therapy and determination of virological response (48–72 weeks). Despite these limitations, progress has been made. The addition of oral ribavirin to standard interferon alfa-2b improved SVR for interferon monotherapy from 9% to 29% for genotype 1, and from 31% to 65% for genotypes 2–3. Peginterferons are the most recent additions to antiviral regimens and two molecules have been approved for the treatment of HCV as monotherapy and in combination with ribavirin.

The process of pegylation involves linkage of interferon to repeating units of non-toxic polyethylene glycol (PEG). The size and linkage of the PEG determines many pharmacological and pharmacokinetic properties of the compound. Peginterferon alfa-2b utilises a 12 kDa PEG linked with a non-covalent bond. This PEG size results in more rapid subcutaneous absorption, wider volume of distribution, and predominantly renal clearance …
Nitroglycerin Treatment May Enhance Chemosensitivity to Docetaxel and Carboplatin in Patients with Lung Adenocarcinoma
Authors: Hiroyasu Yasuda, Katsutoshi Nakayama, Mika Watanabe, Satoshi Suzuki, Hiromi Fuji, Shoji Okinaga, Akio Kanda, Kiyoshi Zayasu, Takahiko Sasaki, Masanori Asada, Tomoko Suzuki, Motoki Yoshida, Shinsuke Yamanda, Daisuke Inoue, Tomohiro Kaneta, Takashi Kondo, Yoshihiro Takai, Hidetada Sasaki, Kazuhiro Yanagihara, Mutsuo Yamaya
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Nitroglycerin may improve the response to chemotherapy in advanced non–small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. Experimental Design: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. Results: The rates of immunoreactive cells for HIF-1α, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1α in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. Conclusions: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1α.
PMO-077 Home enteral tube feeding (HETF): a case burden for the paediatric emergency department (PED)?
Authors: J Smith, C Paxton, P Leonard, D Wilson
Journal: Gut (2012)

<h3>Introduction</h3> The contribution of HETF issues to PED workload is poorly understood. We aimed to evaluate PED attendance records of children receiving HETF (rates, presenting complaints and outcomes). We also aimed to assess possible trends between timing of attendances and hours of service provided by our Children9s Community Nursing (CCN) team. <h3>Methods</h3> We searched 114 606 attendances to PED from April 2008 to March 2011, reviewed all those involving cases on HETF, and correlated with our regional paediatric nutrition support team (NST) records. Day, time and month of attendance plus the presenting triage complaint and outcome were noted. Descriptive results are presented with day of week attendance analysed by the z-test. <h3>Results</h3> There were 364 attendances of 183 patients with a mean (SD) annual point prevalence of HETF patients attending the PED of 23(3.1)%. Mean (SD) attendance rates were 121.3 (23.9) per year representing 61.0(5.2) patients. Presenting complaints included gastrostomy tube (GT) removal (29%), nasogastric tube (NGT) removal (27%), jejunal tube (JT) removal (5%) hardware fault (6%), tube blockage (12%), infection (9%), leakage (4%), malposition (5%) or other (3%). 324 (89%) patients were discharged home and 36 (11%) admitted, mostly for surgical reinsertion. More patients attended on Sundays than any other day of the week (p=0.045); December and January were the busiest months. Peak attendance time was 17:00–18:00; 43% attended out with CCN service hours (08:00–18:00). Most NGT and GT (64%) were reinserted in PED by medical, surgical or nursing staff. Imaging (fluoroscopy; chest x-ray) was required in 29 patients. Topical or enteral antibiotics were prescribed for 22 patients. No action or a simple flush was required in 24 and eight returned the following morning for placement. 20 repair kits for hardware problems were used. <h3>Conclusion</h3> Over 20% of HETF attend PED annually with feeding tube-related problems; 43% attend out with CCN service hours. Significantly higher attendance rates on the day without CCN service cover highlights a flaw in this service design, given the simple problems that occur usually do not need PED expertise and resources. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Saavedra H</b>, <i>et al.</i> Gastrostomy tube related complaints in the pediatric emergency department. <i>Pediatr Emerg Care</i> 2009;<b>25</b>:728–32.
Chest physiotherapy in cystic fibrosis: a comparative study of autogenic drainage and the active cycle of breathing techniques with postural drainage.
Authors: S Miller, D O Hall, C B Clayton, R Nelson
Journal: Thorax (1995)

BACKGROUND--Autogenic drainage has been suggested as an alternative method of chest physiotherapy in patients with cystic fibrosis. In this study autogenic drainage was compared with the active cycle of breathing techniques (ACBT) together with postural drainage. METHODS--Eighteen patients with cystic fibrosis took part in a randomised two-day crossover trial. There were two sessions of one method of physiotherapy on each day, either autogenic drainage or ACBT. The study days were one week apart. On each day the patients were monitored for six hours. Mucus movement was quantified by a radioaerosol technique. Airway clearance was studied qualitatively using xenon-133 scintigraphic studies at the start and end of each day. Expectorated sputum was collected during and for one hour after each session of physiotherapy. Pulmonary functions tests were performed before and after each session. Oxygen saturation (SaO2) and heart rate were measured before, during, and after each session. RESULTS--Autogenic drainage cleared mucus from the lungs faster than ACBT over the whole day. Both methods improved ventilation, as assessed by the xenon-133 ventilation studies. No overall differences were found in the pulmonary function test results, but more patients had an improved forced expiratory flow from 25% to 75% with autogenic drainage, while more showed an improved forced vital capacity with ACBT. No differences were found in sputum weight and heart rate, nor in mean SaO2 over the series, but four patients desaturated during ACBT. CONCLUSIONS--Autogenic drainage was found to be as good as ACBT at clearing mucus in patients with cystic fibrosis and is therefore an effective method of home physiotherapy. Patients with cystic fibrosis should be assessed as to which method suits them best.
Tissue Oxygenation, Venous Ulcers and Fibrin Cuffs
Authors: R Mani, J E White, D F Barrett, P W Weaver
Journal: Journal of the Royal Society of Medicine (1989)

Skin oxygen tension (TcPO2) was measured at 43 degrees C on patients (n = 27) with venous ulcers. Measurements were made at ulcer edge and proximally on the same limb for control. Similar measurements were also made on healthy volunteers (n = 14) in the medial aspects of the distal third of the legs. TcPO2 at ulcer edge was significantly lower (P = 0.001) than control values which in turn were lower than that measured on healthy volunteers. TcPO2 reflects skin nutrition. While low TcPO2 at ulcer edges might be the result of pericapillary barriers to oxygen transport, the control values measured on apparently normal skin suggest the need for further studies.
The Broken Heart: Suicidal Ideation in Bereavement
Authors: Margaret Stroebe, Wolfgang Stroebe, Georgios Abakoumkin
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This report examined suicidal behavior during bereavement. METHOD: Suicidal ideation was examined in a group of 60 recently bereaved widows and widowers compared to 60 individually matched married comparison subjects. RESULTS: Suicidal ideation was higher among widowed people than married people and was most excessive for widows. The effect disappeared when there was control for emotional loneliness. Social support did not buffer bereaved individuals against suicidal ideation but reduced suicidal ideation among the married and bereaved alike. CONCLUSIONS: Bereaved persons are at excess risk of suicidal ideation compared to nonbereaved people. Heightened suicidal ideation in bereavement is associated with extreme emotional loneliness and severe depressive symptoms.
Coronary Artery Bypass Grafts in 109 Autopsied Patients
Authors: G. William Moore, Grover M. Hutchins
Journal: JAMA (1981)

The natural history of coronary artery bypass grafts (CABGs) is poorly understood. In 109 hearts with CABGs, examined after postmortem coronary arteriography and fixation in distention from patients autopsied at The Johns Hopkins Hospital, we studied the 236 grafted coronary arteries for graft and anastomosis patency and operative myocardial injury in the distribution of the distal anastomosis. Of the 30 patients who died at operation, 71 of 72 (99%) had patent grafts; of 61 who died within one month, 120 of 131 (92%) had patent grafts; and of 18 who died one to 70 months after surgery 20 of 33 (61%) had patent grafts. The distal anastomosis site was open in 184 of 211 (87%) patent grafts but in only 13 of 25 (52%) nonpatent grafts. Regional contraction-band necrosis was found in 83 of 184 (45%) with patent graft and distal anastomosis, but in only 11 of 52 (21%) that were closed. Five closed distal anastomoses, but none that were open, had coagulation necrosis. Since the introduction of cold potassium chloride cardioplegia, significantly less regional contraction-band necrosis (19 of 79) (24%) was found than before (80 of 157) (51%). The results of this study show less CABG patency in long-term survivors; association of regional contraction-band necrosis with patent grafts and of coagulation necrosis with closed grafts; and less operative myocardial injury with current surgical technique.
Impact of Clozapine on Completed Suicide
Authors: Michael J. Sernyak, Rani Desai, Marilyn Stolar, Robert Rosenheck
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Clozapine has been found to be superior to typical neuroleptics in ameliorating the symptoms of refractory schizophrenia. This study evaluated clozapine's effect on the rate of death due to suicide. METHOD: All patients over a 4-year period who initiated treatment with clozapine while hospitalized within the Department of Veterans Affairs (VA) system (N=1,415) were matched with a schizophrenic control group (N=2,830) by propensity scoring—a widely accepted statistical method that has been used relatively little in psychiatric research. Centralized VA databases and a national death registry were used to identify all deaths within the two groups, along with listed causes, for the 3 years after discharge. RESULTS: Veterans exposed to clozapine while inpatients were significantly less likely to die during the follow-up period than those in the control group, but this was entirely attributable to the much lower rate of death due to respiratory disorders in the clozapine group. There were no significant differences in rates of suicide or accidental death. CONCLUSIONS: These results fail to support the hypothesis that clozapine treatment is associated with significantly fewer deaths due to suicide.
Half of 10 000 NHS jobs that may be cut are clinical, survey shows
Authors: A. O'Dowd
Journal: BMJ (2011)

More than half of almost 10 000 NHS posts that have been identified as being under threat of being cut in the next few years in England are clinical, the Royal College of Nursing says.

The BMA is also worried about job losses and service cutbacks as a result.

The college has published new figures from a detailed analysis of 21 NHS trusts that show that 9650 posts could be cut and that 54% of those are clinical posts and include doctors rather than managers and administrative staff.

Care of patients will be damaged as a result, warned the college, as a smaller staff meant fewer services and an inferior NHS. The figures showed …
CADAVERIC RENAL TRANSPLANTATION
Authors: Priscilla Kincaid-Smith, V.C. Marshall, T.H. Mathew, Jennifer Eremin, R.B. Brown, N. Johnson, R.R.H. Lovell, D.G. Mcleish, K.F. Fairley, E.A. Allcock, M.R. Ewing
Journal: The Lancet (1967)
Cardiopulmonary Bypass after 50 Years
Authors: L. Henry Edmunds
Journal: New England Journal of Medicine (2004)

A little more than 50 years ago, a hole inside a human heart was closed, with a machine maintaining life while the surgery was done. Within the next two years, four of eight children survived repair of complicated congenital heart defects in operations involving a similar machine. The heart–lung machine, as it was called, was invented and developed by John and Mary Gibbon (see Figure 1). Simultaneously, Forssmann, Cournand, and Richards developed cardiac catheterization that permitted anatomical and physiological diagnoses of heart disease during life. With the discovery and commercial production of the anticoagulant heparin, these two innovations spawned the modern . . .
The Biology of Cystitis: Host and Bacterial Factors
Authors: M. Sussman, PhD, D. L. Gally, PhD
Journal: Annual Review of Medicine (1999)

Cystitis is caused by a relatively small number of bacterial species. To colonize and grow in the urinary tract, these organisms have developed and acquired special properties (virulence factors) that allow them to overcome the defences of the urinary tract, particularly clearance by urine flow. These virulence factors are unlikely to be required during transmission from host to host, and sometimes their constitutive expression may actually be disadvantageous. Such factors are therefore regulated by the environment and in a coordinate manner to ensure their most appropriate expression for the conditions encountered. This review focuses on the biology of the urinary tract and the bacterial properties necessary to cause cystitis. The regulation of virulence factors at the different stages of the infection is considered, and a general model for the pathogenesis of urinary tract infection is proposed.
Increased κ-opioid receptor expression and function during chronic visceral hypersensitivity
Authors: Patrick A Hughes, Joel Castro, Andrea M Harrington, Nicole Isaacs, Melissa Moretta, Gareth A Hicks, David M Urso, Stuart M Brierley
Journal: Gut (2013)

In a recent article in Gut , Hughes et al 1 identified distinct patterns of immune dysfunction in IBS patients compared with healthy subjects. In particular, they showed that peripheral blood mononuclear cell (PBMC) supernatants from healthy subjects inhibited colonic afferents in a μ-opioid receptor (MOR)-mediated manner. These findings correlated with β-endorphin from T lymphocytes providing an important MOR-mediated antinociceptive influence in the healthy gut.2 Intriguingly, these inhibitory effects were lost with PBMC supernatants from constipation-predominant IBS patients suggesting a loss of MOR-mediated inhibition, coupled with increased excitatory mediators (TNF-α, IL-1β, IL-6), contributes to abdominal pain.1

We evaluated if this alteration was MOR specific or whether it extended to other members of the opioid receptor family. As clinical studies have shown varying outcomes on visceral pain perception with κ-opioid receptor (KOR) agonists,3–5 we postulated KOR expression and function are altered during visceral hypersensitivity. Therefore, we determined if the peripherally restricted selective KOR agonist, asimadoline, was able to modify colonic nociceptor function in health and during inflammatory and postinflammatory chronic visceral mechanical hypersensitivity (CVH).6

We performed in vitro afferent recordings from mouse splanchnic high-threshold nociceptors, which respond to focal compression and noxious stretch/distension.1 ,6 …
Predictors for outcome of failure of balloon dilatation in patients with achalasia
Authors: J. Alderliesten, J. M. Conchillo, I. Leeuwenburgh, E. W. Steyerberg, E. J. Kuipers
Journal: Gut (2010)

<h3>Background</h3> Pneumatic balloon dilatation (PD) is a regular treatment modality for achalasia. The reported success rates of PD vary. Recurrent symptoms often require repeated PD or surgery. <h3>Objective</h3> To identify predicting factors for symptom recurrence requiring repeated treatment. <h3>Methods</h3> Between 1974 and 2006, 336 patients were treated with PD and included in this longitudinal cohort study. The median follow-up was 129 months (range 1–378). Recurrence of achalasia was defined as symptom recurrence in combination with increased lower oesophageal sphincter (LOS) pressure on manometry, requiring repeated treatment. Patient characteristics, results of timed barium oesophagram and manometry as well as baseline PD characteristics were evaluated as predictors of disease recurrence with Kaplan–Meier curves and Cox regression analysis. <h3>Results</h3> 111 patients had symptom recurrence requiring repeated treatment. Symptoms recurred after a mean follow-up of 51 months (range 1–348). High recurrence percentages were found in patients younger than 21 years in whom the 5 and 10-year risks of recurrence were 64% and 72%, respectively. These risks were respectively 28% and 36% in patients with classic achalasia, respectively 48% and 60% in patients without complete obliteration of the balloon9s waist during PD and respectively 25% and 33% in patients with a LOS pressure greater than 10 mm Hg at 3 months post-dilatation. These four predictors remained statistically significant in a multivariable Cox analysis. <h3>Conclusion</h3> Although PD is an effective primary treatment in patients with primary achalasia, patients are at risk of recurrent disease, with this risk increasing during long-term follow-up. Young age at presentation, classic achalasia, high LOS pressure 3 months after PD and incomplete obliteration of the balloon9s waist during PD are the most important predicting factors for the need for repeated treatment during follow-up. Patients who meet one or more of these characteristics may be considered earlier for alternative treatment, such as surgery.
Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor
Authors: Liron Zehavi, Roi Avraham, Aviv Barzilai, Dalia Bar-Ilan, Roy Navon, Yechezkel Sidi, Dror Avni, Raya Leibowitz-Amit
Journal: Molecular Cancer (2012)

Metastatic melanoma is a devastating disease with limited therapeutic options. MicroRNAs (miRNAs) are small non coding RNA molecules with important roles in post-transcriptional gene expression regulation, whose aberrant expression has been implicated in cancer.We show that the expression of miRNAs from a large cluster on human chromosome 14q32 is significantly down-regulated in melanoma cell lines, benign nevi and melanoma samples relative to normal melanocytes. This miRNA cluster resides within a parentally imprinted chromosomal region known to be important in development and differentiation. In some melanoma cell lines, a chromosomal deletion or loss-of-heterozygosity was observed in the cis-acting regulatory region of this cluster. In several cell lines we were able to re-express two maternally-induced genes and several miRNAs from the cluster with a combination of de-methylating agents and histone de-acetylase inhibitors, suggesting that epigenetic modifications take part in their silencing. Stable over-expression of mir-376a and mir-376c, two miRNAs from this cluster that could be re-expressed following epigenetic manipulation, led to modest growth retardation and to a significant decrease in migration in-vitro. Bioinformatic analysis predicted that both miRNAs could potentially target the 3'UTR of IGF1R. Indeed, stable expression of mir-376a and mir-376c in melanoma cells led to a decrease in IGF1R mRNA and protein, and a luciferase reporter assay indicated that the 3'UTR of IGF1R is a target of both mir-376a and mir-376c.Our work is the first to show that the large miRNA cluster on chromosome 14q32 is silenced in melanoma. Our results suggest that down-regulation of mir-376a and mir-376c may contribute to IGF1R over-expression and to aberrant negative regulation of this signaling pathway in melanoma, thus promoting tumorigenesis and metastasis.