tbuckley/cabot-search huggingface dataset:
Morphine Modulates Contractile Responses and Neurokinin A-LI Release Elicited by Electrical Field Stimulation or Capsaicin in a Guinea Pig Bronchial-tube Preparation
Authors: Eva G. Lindström, Rolf G. G. Andersson
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Excitatory nonadrenergic, noncholinergic (e-NANC) bronchoconstrictor responses have been shown to be mediated by the release of tachykinins from sensory nerves. We investigated whether bronchial-tube contractions evoked by electrical-field stimulation (EFS) or capsaicin coincided with the release of neurokinin A (NKA). We also studied the modulatory action of morphine and the ability of naloxone to affect these responses. We used a guinea pig bronchial-tube preparation denuded of epithelium. The method allows simultaneous measurement of smooth-muscle tension and mediator release. A significant release of NKA-LI, at 37.3% above the basal level, was detected in response to EFS. Morphine pretreatment was found to inhibit the release, and such inhibition was not prevented by naloxone. Contractile responses to EFS coincided with the NKA-LI release. Capsaicin stimulation evoked a significant release (35.4%) of NKA-LI, and this release was accompanied by contractions. Treatment with morphine decreased capsaicin-induced responses, and naloxone reversed the inhibitory effect. In conclusion, both capsaicin- and EFS-induced e-NANC responses were inhibited by morphine treatment. This indicates presynaptic inhibition of tachykinin release from sensory nerves. Furthermore, the ability of naloxone to reverse this inhibitory effect differed in capsaicin- and EFS-challenged preparations.
Beyond the Monofilament for the Insensate Diabetic Foot
Authors: Yadon Arad, Vivian Fonseca, Anne Peters, Aaron Vinik
Journal: Diabetes Care (2011)

Foot ulcers in patients with diabetes lead to infections, amputations, and high costs, and their prevention is a stated goal of the American Diabetes Association. To assess the benefits of various interventions on the prevention of future diabetic foot ulcers, we searched for and reviewed all randomized clinical trials (RCTs) on the prevention of diabetic foot ulcers and evaluated their efficacy and scientific validity on the basis of an established systemic grading system. Only 13 RCTs were identified. All involved secondary prevention or a mixture of primary and secondary prevention. Most were small and of poor quality, with negative studies generally being of better quality than positive studies. Of all methods proposed to prevent diabetic foot ulcers, only foot temperature-guided avoidance therapy was found beneficial in RCTs, although this needs to be validated in other populations. These observations only apply to high-risk populations, and the benefits to the general population with diabetes are unclear.

### Introduction

Diabetic foot ulcers are the cause of immense suffering and health system costs (1). The lifetime risk of a person with diabetes developing a foot ulcer may be as high as 25%, whereas the annual incidence of foot ulcers is as high as 2% (2–6). Multiple component causes, including peripheral neuropathy, peripheral vascular disease (PVD), foot deformity, and smoking, interact in the causal pathway to foot ulceration. In several cross-sectional and retrospective studies, the prevalence of PVD and peripheral neuropathy in patients was found to be as high as 40%. However, no prospective study clearly documented their relative contribution. This review is concerned primarily with clinical trials on the prevention of foot ulcers in the neuropathic, or insensate, foot.

Several physiologic measurements of the presence and degree of peripheral neuropathy have been shown to be predictive of the risk of future foot ulcer in …
Quantification of regional lymph node involvement in lung cancer
Authors: R. Rami-Porta
Journal: Thorax (2011)

Regional lymph node involvement in lung cancer is heterogeneous. From micrometastases in intrapulmonary lymph nodes—coded as N1(mi)—to bulky contralateral nodal disease—coded as N3—the different situations in between vary in anatomic extent and prognosis. However, regardless of the amount of tumour burden in the regional lymph nodes, the present nodal staging of the tumour, node and metastases (TNM) classification of lung cancer defines the extent of nodal involvement solely via anatomic location.1

Several studies have found that within every N category, there are prognostic modifiers. Thus, for pathologically staged I tumours, the number of removed lymph nodes at thoracotomy seems to have prognostic impact, although the cut-off varies in different studies from six to more than 15 removed lymph nodes.2 3 Within the N1 category, involvement of hilar (main bronchi) lymph nodes has been consistently associated with worse prognosis compared with involvement of intrapulmonary lymph nodes.4 5 Other indicators of worse prognosis in N1 disease are macroscopic nodal involvement and multiple nodal involvement,6 involvement of multiple nodal stations,7 and metastatic involvement—as opposed to direct nodal invasion, at least, in squamous cell carcinomas.8 As for N2 disease, skip pathologic (p) N2 (ie, pN2 without pN1 disease) is associated with better prognosis than pN2 with pN1.9 Single nodal station pN2 also has better prognosis than multiple nodal station pN2.10 Clinically evident multilevel N2 disease and bulky disease also have an adverse effect on prognosis, as well as the involvement of the highest mediastinal lymph node and extranodal extension. Even the specific nodal involvement depending on the lobar location of the primary tumour seems to have prognostic impact: superior mediastinal and aortic nodal disease with right and left upper lobe tumours, respectively, seem to have a better prognosis than the involvement of lower mediastinal nodes with …
Oxygen Radicals Can Induce Preconditioning in Rabbit Hearts
Authors: Isabella Tritto, Davide D’Andrea, Nicola Eramo, Annalisa Scognamiglio, Ciro De Simone, Anna Violante, Annamaria Esposito, Massimo Chiariello, Giuseppe Ambrosio
Journal: Circulation Research (1997)

Abstract Indirect evidence suggests that oxygen radicals may contribute to ischemic preconditioning. We directly investigated whether exposure to oxygen radicals per se, in the absence of ischemia, could reproduce the beneficial effects of ischemic preconditioning on infarct size and on postischemic contractile dysfunction. In one branch of the study, isolated rabbit hearts underwent 30 minutes of total global ischemia and 45 minutes of reperfusion (n=6, control group). A second group, before ischemia/reperfusion, was exposed for 5 minutes to a low flux of oxygen radicals generated by purine/xanthine oxidase (P/XO), followed by a 15-minute washout (n=6). Oxygen radical pretreatment significantly improved postischemic recovery of contractile function. We then investigated in another branch of the study whether this preconditioning effect would also reduce infarct size and whether it was mediated by protein kinase C activation. Control hearts were subjected to coronary artery occlusion for 30 minutes, followed by 2.5 hours of reperfusion (n=6). A second group, before coronary occlusion, was exposed to oxygen radicals and washout as described (n=8). A third group was subjected to oxygen radical infusion, but an inhibitor of protein kinase C (polymyxin B, 50 μmol/L) was administered throughout subsequent ischemia (n=7). A fourth group was exposed to oxygen radicals in the presence of scavengers (superoxide dismutase, 250 U/mL; catalase 500, U/mL; n=8). Pretreatment with oxygen radicals markedly reduced infarct size, from 65±19% of risk region in controls to 12±4% ( P &lt;.05). Protein kinase C inhibition significantly attenuated this effect (infarct size, 37±9% of risk region; P &lt;.05 versus P/XO; P =NS versus controls). Oxygen radical–induced preconditioning was prevented by scavengers (infarct size, 55±14% of risk region; P &lt;.05 versus P/XO; P =NS versus P/XO+polymyxin B). Our data show that in the absence of ischemia, exposure to low concentrations of oxygen radicals can reproduce the beneficial effects of ischemic preconditioning on infarct size and postischemic recovery of left ventricular function. Thus, oxygen radicals might be potential contributors to ischemic preconditioning.
Pathophysiological relevance of apical large-conductance Ca2+-activated potassium channels in pancreatic duct epithelial cells
Authors: V. Venglovecz, P. Hegyi, Z. Rakonczay, L. Tiszlavicz, A. Nardi, M. Grunnet, M. A. Gray
Journal: Gut (2010)

<h3>Background</h3> Acute pancreatitis is among the few inflammatory diseases for which no specific pharmacological treatment is available. It has previously been shown that bile acids alter pancreatic ductal secretion and these effects are probably involved in the pathogenesis of bile-induced pancreatitis. <h3>Objective</h3> To understand the mechanism responsible for bile-induced hypersecretion and, in particular, to identify the molecular target for bile acids in native pancreatic duct epithelial cells (PDECs). <h3>Methods</h3> Patch clamp recordings and spectrofluorimetry were used to measure whole cell currents and rates of HCO<sub>3</sub><sup>−</sup> secretion, respectively, from isolated guinea pig pancreatic ducts. Expression of ion channels and receptors was investigated by immunohistochemistry/immunofluorescence of intact pancreatic tissue. <h3>Results</h3> Exposing PDECs to chenodeoxycholate (CDC, 100 μM) reversibly increased whole cell K<sup>+</sup> currents and hyperpolarised cell membrane potential. Bile acid-stimulated K<sup>+</sup> currents were inhibited by Ba<sup>2+</sup> (2 mM), iberiotoxin (100 nM), and suppressed by strong intracellular Ca<sup>2+</sup> buffering. Luminally applied iberiotoxin also blocked CDC-stimulated HCO<sub>3</sub><sup>−</sup> secretion from microperfused ducts; however, the inhibitor did not influence the stimulatory effect of secretin, carbachol or luminally applied ATP. The specific large-conductance Ca<sup>2+</sup>-activated potassium (BK) channel activator, NS11021, induced a similar increase in HCO<sub>3</sub><sup>−</sup> secretion to CDC. Immunohistochemical analysis showed strong BK channel protein expression on the apical membrane of PDECs, while the G-protein-coupled bile acid receptor-1 was not detected in PDECs, but was present in acinar cells. <h3>Conclusion</h3> It was shown for the first time that BK channels (i) are expressed at the apical membrane of guinea pig PDECs; (ii) have a crucial role in regulating HCO<sub>3</sub><sup>−</sup> secretion and (iii) are also essential for the bile acid-induced hypersecretion and, therefore, underlie the response of the pancreas to this noxious agent.
Genetic Basis of Lipodystrophies and Management of Metabolic Complications
Authors: Anil K. Agarwal, Abhimanyu Garg
Journal: Annual Review of Medicine (2006)

Selective loss of body fat is the hallmark of patients with lipodystrophies. Among genetic lipodystrophies, fat loss is observed either from birth, as in congenital generalized lipodystrophy, or later in life, as in familial partial lipodystrophy. The extent of fat loss also varies among subtypes of lipodystrophies. Patients develop hyperinsulinemia, acanthosis nigricans, hypertriglyceridemia, diabetes mellitus, and hepatic steatosis. Defects in several genes, such as those encoding an enzyme (AGPAT2), a nuclear receptor (PPARγ), a nuclear lamina protein (LMNA) and its processing endoprotease (ZMPSTE24), a kinase (AKT2), and a protein of unknown function (BSCL2), have been found in patients with genetic lipodystrophies. Additional loci remain to be discovered. We discuss features of autosomal recessive and dominant types of lipodystrophies and therapeutic interventions available for these patients.
Hemodynamic Effects of Hyperbaric Oxygenation in Experimental Acute Myocardial Infarction
Authors: LESLIE A. KUHN, HOWARD J. KLINE, MICHAEL WANG, TAKASHI YAMAKI, JULIUS H. JACOBSON
Journal: Circulation Research (1965)

The hemodynamic effects of hyperbaric oxygenation were investigated in anesthetized dogs with acute myocardial embolism and infarction produced by injecting plastic spheres 325 micra in diameter. In 50 "control" animals with acute myocardial infarction induced while breathing either air at one atmosphere, 100% oxygen at one atmosphere or 7% oxygen at three atmospheres, 24-hour mortality was 85 to 90%. In 23 animals that received the same dose of microspheres and breathed 95 to 100% oxygen at three atmospheres for two hours following embolization, there was significantly less 24-hour mortality (30%), less ventricular fibrillation, and less advanced atrioventricular block. Hyperbaric oxygenation afforded protection against immediate mortality from ventricular fibrillation and also against later death, in shock, occurring within 24 hours of coronary embolization but after the immediate postembolization period had passed. In the animals exposed to hyperbaric oxygenation, declines of cardiac output and of central aortic pressure occurring 60 and 90 minutes after coronary embolization were significantly less than in the other animals. In normal animals, hyperbaric oxygenation reduced cardiac output moderately, increased systemic vascular resistance, and elevated aortic pressure slightly. The anatomic extent of the infarction did not differ detectably between the "control" animals and those treated with hyperbaric oxygenation. It is concluded that hyperbaric oxygenation provides protection against mortality in the early period after coronary embolization by preventing ventricular fibrillation. In addition, prevention of major declines in aortic pressure and cardiac output during the later postembolization period in the group with hyperbaric oxygenation was associated with diminished rates of late mortality.
Nutrition: risk factors for osteoarthritis
Authors: T. MCALINDON, D. T FELSON
Journal: Annals of the Rheumatic Diseases (1997)

LeadersNutrition: risk factors for osteoarthritis Questions about the role of diet in the prevention and treatment of their joint disorder may be among the most frequent posed by patients with osteoarthritis (OA).Interestingly, while there are thousands of lay publications recommending various arthritis diets, physicians have little information to oVer based on scientific studies. 1 Arguably, in no other aspect of rheumatology is public and medical interest so discrepant.Indeed, the traditional medical approach has been to counsel patients that, other than diets promoting weight loss, scientific research has produced no evidence to suggest that any particular nutritional intervention might be helpful for OA. 2 In fact, studies do suggest pathways through which nutritional factors might influence the natural history of OA. Diet and obesityOverweight people are at considerably increased risk for the development of OA in their knees, and may also be more susceptible to both hip and hand joint involvement. 3s overweight people do not necessarily have increased load across their hand joints, investigators have wondered for decades whether systemic factors, such as dietary factors or other metabolic consequences of obesity, may mediate some of this association.Indeed, early laboratory studies using strains of mice and rats seemed to suggest an interaction between body weight, genetic factors, and diet, although attempts to demonstrate a direct eVect of dietary fat intake proved inconclusive. 4 5Irrespective of the mechanism, it seems reasonable to infer that weight reduction, through dietary or other means, may reduce a person's risk for the development or progression of OA.Observational data from the Framingham OA Study support this notion and suggest that weight loss of approximately 5 kg will reduce a person's risk for the development of knee OA over the subsequent 10 years by 50%. 6nfortunately, dietary intervention for obesity in uncontrolled environments is often costly, unpleasant, and frequently ineVective, particularly in the long term. 7Furthermore, it is increasingly apparent from studies of the genetics of obesity, and the biology and physiology of weight regulation, that obesity is a disorder with many more facets than the simplistic equation relating energy output with expenditure. 8 9In light of these facts, and the numerous adverse medical and psychological eVects associated with dieting, many investigators now believe that weight loss through dietary intervention alone is diYcult to justify. 10
Just When You Thought the Fluorouracil Debate Was Over: <i>S</i>-1 and Gastric Cancer
Authors: David Ilson
Journal: Journal of Clinical Oncology (2005)

Despite a decline in incidence in the United States and Western Europe, gastric cancer is common worldwide and remains the second leading cause of cancer-related death.In a shift in the epidemiology of gastric cancer, adenocarcinomas of the esophagus and gastroesophageal junction are increasing at a dramatic rate in the United States and Western Europe, and represent an even more virulent disease entity. 1 The pattern of more distal gastric cancer elsewhere in the world may be a function of rates of infection by Helicobacter pylori, dietary practices, and potential dietary deficiency in micronutrients such as selenium and vitamin C. The predominance of adenocarcinoma of the esophagus and gastroesophageal junction in the West may reflect population trends in obesity and tobacco abuse, and paradoxically, a decrease in Helicobacter infection that may increase the risk of esophageal reflux disease. 2 Because of the absence of effective screening, patients with gastric cancer in the United States usually present with symptomatic and either locally advanced or metastatic disease.High rates of recurrence after surgery have engendered decades of clinical trials evaluating the use of adjuvant chemotherapy, with or without radiation.Fortunately, recent clinical trials have made advances with the validation of the use of systemic chemotherapy to improve survival.Intergroup trial 116 showed that postoperative bolus fluorouracil (FU), leucovorin, and radiation therapy improved survival compared with surgery alone, despite the relative inactivity for FU and leucovorin in metastatic disease. 3Although postoperative adjuvant chemotherapy alone has failed to affect survival in gastric cancer, pre-and postoperative chemotherapy with epirubicin, cisplatin, and protracted-infusion FU (ECF) without the use of radiation, as recently reported in the MAGIC trial from the United Kingdom, significantly improved survival compared with surgery alone. 4he improvement in survival in recent adjuvant trials, however, is marginal, and the key to further progress is the identification of more active systemic agents in gastric cancer.
A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments
Authors: M Ostensen
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> : To analyse the disease course of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) during and after pregnancy by validated clinical instruments for measurement of disease activity, and assess their usefulness in pregnant patients. <b>Methods:</b> Included were 10 patients with RA and 9 with AS (10 pregnancies). Clinical examination and blood/urine sampling was performed before conception, at each trimester, and weeks 6, 12, and 24 post partum. Assessment of RA was by the RA Disease Activity Index (RADAI), the 44 joint count, and the Health Assessment Questionnaire; assessment of AS by the Bath Ankylosing Spondylitis Activity Index (BASDAI), the Dougados Functional and Articular Index, and a night pain index. Common for all patients were the patient's and physician's global assessment. <b>Results:</b> : Most patients with RA showed sustained or increased improvement of disease activity during pregnancy. Higher disease activity scores were found in the patients with AS with a frequent increase of disease activity in the second trimester and mitigation of symptoms in the third trimester. Analysis specifically for the patient's assessment of pain showed continuously higher pain scores in the patients with AS than in those with RA. Rank correlation showed good to moderate correlation between most clinical measurements and RADAI or BASDAI, respectively. Functional indices were confounded by physiological changes of late pregnancy. <b>Conclusion:</b> RA can be monitored during and after pregnancy by the swollen joint count and RADAI without interference from pregnancy related symptoms, whereas usual measures of disease activity are not always applicable in pregnant patients with AS.
Reply to D.C. Gilbert et al
Authors: Edmund A. Mroz, Arlene A. Forastiere, James W. Rocco
Journal: Journal of Clinical Oncology (2012)

P53, 7 and patients with this tumor type have demonstrated excellent survival with existing protocols such as concurrent chemoradiotherapy or surgery with postoperative radiotherapy.Conversely, non-HPV tumors, harboring a range of mutations, 8 may respond less well to DNA-damaging agents, but patients with these tumors might benefit from the addition of concurrent EGFR blockade to radiotherapy.Data from the recent SPECTRUM (Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer) study of adding another EGFR-targeting monoclonal antibody, panitumumab, 9 suggest that in the metastatic setting at least, only patients with HPV-negative tumors benefit from a combination of palliative chemotherapy and an anti-EGFR strategy.If confirmed in sample sets containing non-HPV tumors treated with EGFR-targeting agents in combination with radiotherapy, this could open the door to the improvements urgently needed in HPV-negative oropharyngeal cancers, where an older demographic and greater burden of comorbidities make the uncomplicated and complete delivery of concurrent chemoradiotherapy challenging.