tbuckley/cabot-search huggingface dataset:
Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: a 3-year interim analysis of the LOTUS trial
Authors: L Lundell, S Attwood, C Ell, R Fiocca, J-P Galmiche, J Hatlebakk, T Lind, O Junghard
Journal: Gut (2008)

<h3>Background:</h3> With the introduction of laparoscopic antireflux surgery (LARS) for gastro-oesophageal reflux disease (GORD) along with the increasing efficacy of modern medical treatment, a direct comparison is warranted. The 3-year interim results of a randomised study comparing both the efficacy and safety of LARS and esomeprazole (ESO) are reported. <h3>Methods:</h3> LOTUS is an open, parallel-group multicentre, randomised and controlled trial conducted in dedicated centres in 11 European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg once daily, which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan–Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol. <h3>Results:</h3> 554 patients were randomised, of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the intention to treat population, p = 0.25 (90% vs 95% per protocol). No major unexpected postoperative complications were experienced and ESO was well tolerated. However, postfundoplication complaints remain a problem after LARS. <h3>Conclusions:</h3> Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD.
Cirrhosis of the liver.
Authors: A. E. Read
Journal: BMJ (1968)

Essentially three main types of cirrhosis are recognized: (1) micronodular, (2) macronodular, and (3) mixed. Primary biliary cirrhosis is a micronodular type of cirrhosis based on chronic biliary obstruction and cardiac cirrhosis is a fine cirrhosis also. No close relationship exists between the cause of cirrhosis and the configuration of the regeneration nodules. Alcoholic cirrhosis is often micronodular; however, regeneration nodules may be large in alcoholics with heavy intermittent drinking habits. Alcoholic cirrhosis, also known as Laennec's Cirrhosis, is a disease that is common where there is a high incidence of alcoholism. The disease is more common in males than in females. The liver is often enlarged and even micronodular type of cirrhosis may be present. The liver often looks greasy and this feature is well demonstrated in histological preparations, which show fatty change in the liver cells. Fatty infiltration is indicative of recent drinking and when drinking stops, the fat disappears. Liver cell damage is variable; however, following a bout of hard drinking, it can be severe with areas of liver cell necrosis and polymorph infiltration.
Macromolecular Interactions and Ion Transport in Cystic Fibrosis
Authors: William B. Guggino, Susan P. Banks-Schlegel
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Cystic fibrosis (CF) is a genetic disease caused by autosomal recessive mutations of the CF transmembrane regulator, CFTR. CFTR functions in the plasma membrane of epithelial cells lining the lung, pancreas, liver, intestines, sweat duct, and the epididymis. The primary problem in CF is that mutations in CFTR affect its ability to be made, processed, and trafficked to the plasma membrane and/or its function as a Cl(-) channel and conductance regulator. Many proteins and processes normally interact with normal CFTR throughout its life cycle and mutant CFTR during the disease process. Understanding the function of these proteins and processes is expected to provide a clearer understanding of how normal CFTR is involved in salt movement and how mutant CFTR is handled by the cell and leads to the pathophysiology of CF. Recently, efforts to find therapies that correct defective CFTR have been intensifying. To facilitate our understanding of normal and mutant CFTR and the identification of new drug targets for developing novel therapies, a panel of experts was convened by the National Heart, Lung, and Blood Institute to explore the critical questions, challenges, and current opportunities to highlight new areas of research that would facilitate a integrated understanding of the processes and proteins that impact CFTR. The meeting highlighted the multiple pathways and interacting proteins involved in CFTR folding and biosynthesis, processing, and trafficking. A number of critical areas for future study were identified. Although these therapies are promising, a big question remains as to whether simply correcting defective CFTR will lead to significant improvement in patient health or whether the symptoms manifested in CF will require therapies in addition to those that target defective CFTR specifically.
Oxygen for relief of dyspnoea in people with chronic obstructive pulmonary disease who would not qualify for home oxygen: a systematic review and meta-analysis: Figure 1
Authors: Hope E Uronis, Magnus P Ekström, David C Currow, Douglas C McCrory, Gregory P Samsa, Amy P Abernethy
Journal: Thorax (2014)

We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register to determine whether oxygen relieves dyspnoea in mildly or non-hypoxemic COPD and included 18 randomised controlled trials (431 participants) in the meta-analysis using Cochrane methodology. Oxygen therapy reduced dyspnoea when compared with medical air; standardised mean difference −0.37 (95% CI −0.50 to −0.24; I<sup>2</sup>=14%). In a priori subgroup and sensitivity analyses, dyspnoea was reduced by continuous oxygen during exertion but not short-burst oxygen therapy. Continuous exertional oxygen can relieve dyspnoea in mildly or non-hypoxemic COPD, but evidence from larger clinical trials is needed.
Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers
Authors: T. R. Rebbeck, A. M. Levin, A. Eisen, C. Snyder, P. Watson, L. Cannon-Albright, C. Isaacs, O. Olopade, J. E. Garber, A. K. Godwin, M. B. Daly, S. A. Narod, S. L. Neuhausen, H. T. Lynch, B. L. Weber
Journal: JNCI Journal of the National Cancer Institute (1999)

The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers.We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth.We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0. 28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery.Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.
Getting the rehabilitation message across: emerging barriers and positive health benefits
Authors: S. M. Smith, M. R. Partridge
Journal: European Respiratory Journal (2009)

The world's press frequently contains stories of failed rehabilitation attempts 1 by media personalities, and popular songs on this topic can galvanize strong views 2. Such events highlight the popularisation of a faulty view that rehabilitation offers only a marginal opportunity for benefit and as such should be avoided at all costs. It is unclear if such scepticism, reinforced by the media, impacts upon those with long-term illness and whether it limits, for example, what pulmonary and cardiac rehabilitation programmes have to offer. In a recent local Primary Care Trust chronic obstructive pulmonary disease (COPD) service evaluation report, patients voiced their concern over the term “rehab” 3 as they believe that there is stigma attached to the term. This previously unrecognised concern may form a new barrier to pulmonary rehabilitation programmes. Clearly, any such concern needs to be addressed as these are interventions of great benefit to our patients 4, 5. However as recruitment and retention of patients into rehabilitation programmes is not easy, as a specialty we need to reflect upon the terminologies we use and how best we “sell” or market these interventions to our patients.

COPD represents a global health burden 6 and will move from being the 12th cause to the 5th cause of disability adjusted-life years lost by the year 2020 7. In the UK, >5% of all deaths have been attributed to COPD and up to one in eight emergency hospital admissions may be due to the condition 8. Patients who experience acute exacerbations of COPD have: 1) more frequent visits to the emergency department and hospitalisation 9, 10; 2) a more rapid decline in lung function 11; and 3) a reduced quality of life 12. Pulmonary rehabilitation, which contains elements of …
Peptide inhibitors of the ice protease family arrest programmed cell death of motoneurons in vivo and in vitro
Authors: C.E. Milligan, D. Prevette, H. Yaginuma, S. Homma, C. Cardwellt, L.C. Fritz, K.J. Tomaselli, R.W. Oppenheim, L.M. Schwartz
Journal: Neuron (1995)
NKG2D Ligand Expression in Human Colorectal Cancer Reveals Associations with Prognosis and Evidence for Immunoediting
Authors: Roger W. McGilvray, Robert A. Eagle, Nicholas F.S. Watson, Ahmad Al-Attar, Graham Ball, Insiya Jafferji, John Trowsdale, Lindy G. Durrant
Journal: Clinical Cancer Research (2009)

NKG2D (natural killer group 2, member D) binds to cellular ligands of the MIC and ULBP/RAET family. These ligands have restricted expression in normal tissue, but are frequently expressed on primary tumors. The role of NKG2D ligands is thought to be important in carcinogenesis but its prognostic effect has not been investigated in such a large cohort.In our study, 462 primary colorectal tumors were screened for the expression of all MIC/ULBP/RAET proteins and NK cell infiltration. Tumor microarray technology was used for the purpose of this investigation.NKG2D ligands were expressed by the majority of colorectal tumors; however, the level of expression varied considerably. High expression of MIC (68 versus 56 months) or RAET1G (74 versus 62 months) showed improved patient survival. Tumors expressing high levels of MIC and RAET1G showed improved survival of 77 months over tumors that expressed high levels of one ligand or low levels of both. High-level expression of all ligands was frequent in tumor-node-metastasis stage I tumors, but became progressively less frequent in stages II, III, and IV tumors. Expression of MIC was correlated with NK cellular infiltration.The observations presented are consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced their expression of NKG2D ligands. The combination of MIC and tumor-node-metastasis stage was found to be the strongest predictor of survival, splitting patients into eight groups and suggesting prognostic value in clinical assessment. Of particular interest were stage I patients with low expression of MIC who had a similar survival to stage III patients, and may be candidates for adjuvant therapy.
Cyclooxygenase-2–dependent lymphangiogenesis promotes nodal metastasis of postpartum breast cancer
Authors: Traci R. Lyons, Virginia F. Borges, Courtney B. Betts, Qiuchen Guo, Puja Kapoor, Holly A. Martinson, Sonali Jindal, Pepper Schedin
Journal: Journal of Clinical Investigation (2014)

Breast involution following pregnancy has been implicated in the high rates of metastasis observed in postpartum breast cancers; however, it is not clear how this remodeling process promotes metastasis. Here, we demonstrate that human postpartum breast cancers have increased peritumor lymphatic vessel density that correlates with increased frequency of lymph node metastases. Moreover, lymphatic vessel density was increased in normal postpartum breast tissue compared with tissue from nulliparous women. In rodents, mammary lymphangiogenesis was upregulated during weaning-induced mammary gland involution. Furthermore, breast cancer cells exposed to the involuting mammary microenvironment acquired prolymphangiogenic properties that contributed to peritumor lymphatic expansion, tumor size, invasion, and distant metastases. Finally, in rodent models of postpartum breast cancer, cyclooxygenase-2 (COX-2) inhibition during the involution window decreased normal mammary gland lymphangiogenesis, mammary tumor-associated lymphangiogenesis, tumor cell invasion into lymphatics, and metastasis. Our data indicate that physiologic COX-2-dependent lymphangiogenesis occurs in the postpartum mammary gland and suggest that tumors within this mammary microenvironment acquire enhanced prolymphangiogenic activity. Further, our results suggest that the prolymphangiogenic microenvironment of the postpartum mammary gland has potential as a target to inhibit metastasis and suggest that further study of the therapeutic efficacy of COX-2 inhibitors in postpartum breast cancer is warranted.
The Design of Covalent Allosteric Drugs
Authors: Ruth Nussinov, Chung-Jung Tsai
Journal: The Annual Review of Pharmacology and Toxicology (2014)

A key issue in drug discovery is how to reduce drug dosage and increase specificity while retaining or increasing efficacy, as high dosage is often linked to toxicity. There are two types of drugs on the market: orthosteric and allosteric. Orthosteric drugs can be noncovalent or covalent. The latter are advantageous because they may be prescribed in lower doses, but their potential off-target toxicity is a primary concern. The chief advantages of allosteric drugs are their higher specificity and their consequently lower chance of toxic side effects. Covalent allosteric drugs combine the pharmacological merits of covalent drugs with the additional benefit of the higher specificity of allosteric drugs. In a recent promising step in therapeutic drug development, allosteric, disulfide-tethered fragments successfully modulated the activity of a protein kinase and K-Ras.
ROC1/RBX1 E3 Ubiquitin Ligase Silencing Suppresses Tumor Cell Growth via Sequential Induction of G2-M Arrest, Apoptosis, and Senescence
Authors: Lijun Jia, Maria S. Soengas, Yi Sun
Journal: Cancer Research (2009)

Regulator of Cullins-1 (ROC1) or Ring Box Protein-1 (RBX1) is a RING component of SCF (Skp-1, cullins, F-box proteins) E3 ubiquitin ligases, which regulate diverse cellular processes by targeting a variety of substrates for degradation. However, little is known about the role of ROC1 in human cancer. Here, we report that ROC1 is ubiquitously overexpressed in primary human tumor tissues and human cancer cell lines. ROC1 silencing by siRNA significantly inhibited the growth of multiple human cancer cell lines via induction of senescence and apoptosis as well as G(2)-M arrest. Senescence induction is coupled with DNA damage in p53/p21- and p16/pRB-independent manners. Apoptosis is associated with accumulation of Puma and reduction of Bcl-2, Mcl-1, and survivin; and G(2)-M arrest is associated with accumulation of 14-3-3sigma and elimination of cyclin B1 and Cdc2. In U87 glioblastoma cells, these phenotypic changes occur sequentially upon ROC1 silencing, starting with G(2)-M arrest, followed by apoptosis and senescence. Thus, ROC1 silencing triggers multiple death and growth arrest pathways to effectively suppress tumor cell growth, suggesting that ROC1 may serve as a potential anticancer target.
Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss
Authors: Paul Poirier, Thomas D. Giles, George A. Bray, Yuling Hong, Judith S. Stern, F. Xavier Pi-Sunyer, Robert H. Eckel
Journal: Circulation (2005)

Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.
Palliative Care Inpatient Service in a Comprehensive Cancer Center: Clinical and Financial Outcomes
Authors: Ahmed Elsayem, Kay Swint, Michael J. Fisch, J. Lynn Palmer, Suresh Reddy, Paul Walker, Donna Zhukovsky, Patti Knight, Eduardo Bruera
Journal: Journal of Clinical Oncology (2004)

Inpatient palliative care units are unavailable in most cancer centers and tertiary hospitals. The purpose of this article is to review the outcomes of the first 344 admissions to the Palliative Care Inpatient Service (PCIS) at our comprehensive cancer center.We retrospectively reviewed our computerized database for clinical and demographic information, length of stay, and hospital billing during the first year of the service's operation.Three hundred twenty patients were admitted during the study period. Their median age was 57 years. The main cancer diagnoses were thoracic or head and neck (44%), gastrointestinal (25%), and hematologic malignancy (8%). The main referral symptoms were pain (44%), nausea (41%), fatigue (39%), and dyspnea (38%). The median length of stay in the PCIS was 7 days (range, 1 to 58 days). Fifty-nine patients died while in the PCIS. However, the overall hospital mortality rate was not increased compared with that in the year before the establishment of the PCIS (3.58% v 3.59%). The mean reimbursement rate for all palliative care charges was approximately 57%, and the mean daily charges in the PCIS were 38% lower than the mean daily charges for the rest of the hospital. Symptom intensity data showed severe distress on admission and significant improvement in the main target symptoms. Most patients were discharged to a hospice.The PCIS has been accepted in our tertiary cancer center on the basis of its clinical utility and financial viability.
The inflammatory markers in psoriasis
Authors: T. Purnak, S. Purnak
Journal: British Journal of Dermatology (2012)

Funding sources: none. Conflicts of interest: none declared. Madam, We read with great interest the article by Romaníet al.1 regarding inflammatory and atherogenic profiles of Spanish patients with psoriasis. The authors carefully studied the metabolic parameters of patients with psoriasis. However, we have some concerns about the design of the study. First of all, although we were completely satisfied with the parameters studied in patients with psoriasis in the study, we could not find any clinical information regarding whether the patients with psoriasis had coronary artery disease or any other atherosclerosis‐related disease. It would be very useful to know these data for the translation of the exact impact of the parameters studied into real clinical practice. Secondly, the authors concluded that ferritin, vitamin B12 and C‐reactive protein (CRP) decreased significantly after narrowband ultraviolet B therapy as the disease improved. However, some drugs commonly used in patients with metabolic syndrome have anti‐inflammatory properties, such as statins, and they decrease the levels of the inflammatory markers, particularly CRP.2 We were wondering whether or not these groups of drugs were excluded from the study.
Effects of Electrical Stimulation on Wound Healing in Patients With Diabetic Ulcers
Authors: Lucinda L Baker, Richard Chambers, Sharon K DeMuth, Fernando Villar
Journal: Diabetes Care (1997)

OBJECTIVE To evaluate the effects of two stimulation waveforms on healing rates in patients with diabetes and open ulcers. The hypothesis was that stimulus waveforms with minimal polar characteristics would provide significant healing for this patient sample. RESEARCH DESIGN AND METHODS This was a prospective study that enrolled 80 patients with open ulcers. Patients received stimulation with either an asymmetric biphasic (A) or symmetric biphasic (B) square-wave pulse. Amplitudes were set to activate intact peripheral nerves in the skin. Two other groups received either very low levels of stimulation current (MC), or no electrical stimulation (C). When combined these groups were referred to as the control group. Treatment was carried out daily until the wound healed, the patient withdrew from the study, or the physician changed the overall wound management program. Average healing rates were calculated from weekly measures of the wound perimeter and were used for statistical comparison through a one-way analysis of variance. RESULTS Stimulation with the A protocol significantly increased the healing rate, enhancing healing by nearly 60% over the control rate of healing. Stimulation with the B protocol did not increase the healing rate when compared with control subjects. CONCLUSIONS Electrical stimulation, given daily with a short pulsed, asymmetric biphasic waveform, was effective for enhancement of healing rates for patients with diabetes and open ulcers.