tbuckley/cabot-search huggingface dataset:
Combining Capecitabine and Gemcitabine in Patients With Advanced Pancreatic Carcinoma: A Phase I/II Trial
Authors: Viviane Hess, Marc Salzberg, Markus Borner, Rudolf Morant, Arnaud D. Roth, Christian Ludwig, Richard Herrmann
Journal: Journal of Clinical Oncology (2002)

Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC.This multicenter study included patients naïve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD.Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients.The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.
Anaphylactoid Shock Induced by Oral Penicillin and Resulting in Gerstmann's Syndrome
Authors: A. M. Fox
Journal: BMJ (1965)

No case of anaphylactoid shock due to oral penicillin has been reported hitherto in the British literature, although cases have been noted overseas.The present case, in which Gerstmann's syndrome features as a residuum of the reaction, is thus of no small clinical interest. Case ReportA 46-year-old married woman was admitted to East Ham Memorial Hospital under the care of Dr. Harold W. Salmon on 26 June 1964.Earlier that day she had consulted her family doctor on account of severe pain at the root of the nose which had been present, together with mild malaise, for the previous week.As she had been thought previously to have suffered from sinusitis, phenoxymethylpenicillin (Distaquaine V-K) was prescribed.Immediately after placing one tablet (250 mg.) in her mouth she complained of " a terrible feeling," developed severe and generalized pruritus, and rapidly lost consciousness.Her family doctor was hurriedly summoned, and after administering nikethamide (1 ml.) he sent her to hospital.When first seen, 45 minutes after the attack, she was unconscious, but responded to painful stimuli with purposeless movements.There was intense congestion of the head and neck, marked conjunctival injection, and swelling of the tongue.The finger tips were cyanosed.Blood-pressure was variable, and was unrecordable when she was first seen.The pulse was regular at 64.The temperature was not taken.The limb tone tended to be flaccid and symmetrical, but all tendon jerks were elicited ; the left plantar response was extensor ; both pupils were constricted ; no other localizing signs were obtained.The heart, lungs, and abdomen showed no clinical abnormalities.Past History.-There had been no serious illnesses, but she had
Can palliative care teams relieve some of the pressure on acute services?
Authors: F. Murtagh
Journal: BMJ (2014)

All the evidence points that way; commissioners take note

Specialist palliative care teams are those with palliative care as their core daily work. They are multidisciplinary teams, have specialist skills and experience, and deliver palliative care both directly and indirectly; directly by providing care to patients and families, and indirectly by supporting other professionals to deliver such care.1

Providers, commissioners, and funders of health services need to know whether specialist palliative care teams make a difference and, if so, how. They need to know this, not only to determine whether these teams make a positive difference for patients and families, but also because of the urgent need for health services across the world to do things differently; to shift the emphasis from acute care to better coordinated care at home and across the interface between acute and community care. In this issue of The BMJ (doi:10.1136/bmj.g3496) Seow and colleagues report a retrospective cohort study from Canada which suggests that community based specialist palliative care teams are effective in reducing use of acute care services (hospitalisation and emergency department attendance) in the last weeks of life.2 This adds to growing evidence that specialist palliative care teams not only improve patients’ symptom control, quality of life, and satisfaction with care, but can change patterns of …
Caring for indigenous Australian children with asthma
Authors: A B CHANG
Journal: Thorax (2000)

We applaud Dr Partridge's recent thought provoking editorial1 which is timely with recent articles focusing on medicine, poverty, and marginalised groups.2 We wish to add that the issues raised by Partridge are also highly relevant in Australia with respect to indigenous Australians who have unacceptably high levels of morbidity and mortality compared with non-indigenous Australians.3 Also, in addition to the influence of the doctor/patient relationship on health care, …
Activation of lymphokine genes in T cells: Role of cis-acting DNA elements that respond to T cell activation signals
Authors: Naoko Arai, Yoshiyuki Naito, Mitsuo Watanabe, Esteban S. Masuda, Yuko Yamaguchi-Iwai, Akio Tsuboi, Toshio Heike, Ikuo Matsuda, Kyoko Yokota, Naoko Koyano-Nakagawa, Hyun Jun Lee, Masaaki Muramatsu, Takashi Yokota, Ken-Ichi Arai
Journal: Pharmacology & Therapeutics (1992)
Phagocytes in cell suspensions of human colon mucosa.
Authors: W Beeken, I Northwood, C Beliveau, D Gump
Journal: Gut (1987)

Because little is known of the phagocytes of the human colon we enumerated these cells in mucosal suspensions and studied their phagocytic activity. Phagocyte rich suspensions were made by EDTA collagenase dissociation followed by elutriation centrifugation. Phagocytosis was evaluated by measuring cellular radioactivity after incubation of phagocytes with 3H-adenine labelled E coli ON2 and checked microscopically. Dissociation of normal mucosa from colorectal neoplasms yielded means of 1.9 X 10(6) eosinophils, 1.4 X 10(6) macrophages and 2 X 10(5) neutrophils per gram of mucosa. Visually normal mucosa of inflammatory states yielded 2.2 X 10(6) eosinophils, 2.3 X 10(6) macrophages and 7 X 10(5) neutrophils per gram of mucosa. Phagocyte rich suspensions of normal mucosa from tumour patients phagocytosed 21.8% of a pool of opsonised tritiated E coli ON2 and by microscopy 100% of mucosal neutrophils ingested bacteria, 83% of eosinophils were phagocytic, and 53% of macrophages contained bacteria. These results suggest that in the human colonic mucosa, the eosinophil is more abundant than the macrophage and the per cent of those cells exhibiting phagocytosis is intermediate between that of the macrophage and the neutrophil. Thus these three types of cells are actively phagocytic and share the potential for a major role in host defence against invasive enteric bacteria.
Multicenter Phase II Trial of ABI-007, an Albumin-Bound Paclitaxel, in Women With Metastatic Breast Cancer
Authors: Nuhad K. Ibrahim, Brian Samuels, Ray Page, Dinesh Doval, Kirtikumar M. Patel, S.C. Rao, Madhavan Krishnan Nair, Paul Bhar, Neil Desai, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2005)

Purpose ABI-007 is a novel nanoparticle, albumin-bound paclitaxel that is free of solvents. This multicenter phase II study was designed to evaluate the efficacy and safety of ABI-007 for the treatment of metastatic breast cancer (MBC). Patients and Methods Sixty-three women with histologically confirmed and measurable MBC received 300 mg/m 2 ABI-007 by intravenous infusion over 30 minutes every 3 weeks without premedication. Forty-eight patients received prior chemotherapy; 39 patients received no prior treatment for metastatic disease. Results Overall response rates (complete or partial responses) were 48% (95% CI, 35.3% to 60.0%) for all patients. For patients who received ABI-007 as first-line and greater than first-line therapy for their metastatic disease, the respective response rates were 64% (95% CI, 49.0% to 79.2%) and 21% (95% CI, 7.1% to 42.1%). Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported despite the lack of premedication. Toxicities observed were typical of paclitaxel and included grade 4 neutropenia (24%), grade 3 sensory neuropathy (11%), and grade 4 febrile neutropenia (5%). Patients received a median of six treatment cycles; 16 patients had 25% dose reductions because of toxicities, and two of these patients had subsequent dose reductions. Conclusion ABI-007, the first biologically interactive albumin-bound form of paclitaxel in the nanoparticle state, uses the natural carrier albumin rather than synthetic solvents to deliver paclitaxel and allows for safe administration of high paclitaxel doses without premedication, resulting in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy.
Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways
Authors: Chang Min Yoon, Bok Sil Hong, Hyung Geun Moon, Seyoung Lim, Pann-Ghill Suh, Yoon-Keun Kim, Chi-Bom Chae, Yong Song Gho
Journal: Blood (2008)
Cells isolated from the human cortical interstitium resemble myofibroblasts and bind neutrophils in an ICAM-1--dependent manner.
Authors: A Clayton, R Steadman, J D Williams
Journal: Journal of the American Society of Nephrology (1997)

Progressive renal disease is frequently accompanied by renal interstitial inflammation and fibrosis in which the activity of resident fibroblasts may be of central importance. Because there are relatively few fibroblasts in the normal cortical interstitium and there is no specific marker to permit their identification, these cells have proved difficult to characterize in vitro. In this study, these cells were isolated and established in culture, using CD90 as a positive selection marker. Antibodies to CD90 bound to tubular epithelial cells and fibroblasts, but not to glomerular cells in kidney sections. In culture, only fibroblasts were CD90-positive. These normal renal cortical fibroblasts (RCF) were alpha-smooth muscle actin- and vimentin-positive, but desmin-, cytokeratin-, and factor VIII-negative, identifying them as myofibroblasts. They expressed platelet-derived growth factor alpha and beta receptors; CD44; and alpha 2, beta 1, and beta 3 integrin chains: this combination of markers was also characteristic of fibroblasts in sections of normal cortex. These cells were positive for ICAM-1 but negative for VCAM-1. Similarly, proliferating or growth-arrested renal cortical fibroblasts (RCF) in culture expressed ICAM-1 but not VCAM-1. The expression of VCAM-1 was detected, however, and that of ICAM-1 was increased on fibroblasts associated with inflammatory infiltrates in sections from fibrotic kidneys, and ICAM-1 and VCAM-1 were up-regulated on RCF in culture after incubation with increasing doses of interleukin-1 beta or tumor necrosis factor alpha (maximum between 24 and 48 h). These adhesion molecules were functional, and neutrophils adhered to resting and cytokine-activated RCF. Binding was maximal between 24 and 48 h after cytokine treatment and was inhibited by anti-CD18 antibodies. ICAM-1 is the principal adhesion molecule controlling inflammatory cell infiltration of the interstitium. The study presented here suggests that cortical fibroblasts may be central to the control of this infiltration.
U-Shaped and J-Shaped Relationships Between Serum Insulin and Coronary Heart Disease in the General Population: The Bruneck Study
Authors: Enzo Bonora, Johann Willeit, Stefan Kiechl, Friedrich Oberhollenzer, Georg Egger, Riccardo Bonadonna, Michele Muggeo
Journal: Diabetes Care (1998)

OBJECTIVE To evaluate the relationship existing between serum insulin and coronary heart disease (CHD) in the general population. RESEARCH DESIGN AND METHODS In a cross-sectional survey on atherosclerosis and its risk factors, 500 men and 500 women aged 40–79 years were randomly selected from the population of Bruneck, Italy. Clinical, biochemical, and behavioral risk factors of atherosclerosis were assessed in the 936 subjects who participated in the study. Serum insulin was measured at fasting (n = 888) and 2 h (n = 811, known diabetic subjects were excluded) after an oral glucose load. CHD was ascertained by an abnormal electrocardiogram and/or a history of angina or myocardial infarction. RESULTS Subjects were stratified according to serum insulin quintiles at fasting or 2 h after glucose loading. After adjustment for sex, age, BMI, smoking, physical activity, alcohol intake, and socioeconomic status (analysis of covariance), cardiovascular risk factors clustered in subjects of the top insulin quintile. Multiple logistic regression analysis, including sex and age in model 1, sex, age, BMI, glucose tolerance, socioeconomic status, and behavioral variables in model 2, or this set of variables together with triglycerides and apoproteins Al and B, fibrinogen, and blood pressure status in model 3, revealed a significant association between high serum insulin and CHD when median insulin quintile was used as the reference class. Moreover, low serum insulin levels, such as those found in subjects of the lowest quintile, were independently related to CHD. These results were found either before (model 1) or after (models 2 and 3) adjusting for several covariates. Consistent results were found in men and women, as well as in younger and older subjects. CONCLUSIONS Results of the present study suggest that both hyperinsulinemia and “hypoinsulinemia” are independent indicators of CHD. Furthermore, it is proposed that the relationship between CHD and fasting insulin is U-shaped, whereas that between CHD and postglucose insulin may be J-shaped.
Coronary microvascular dysfunction due to essential thrombocythemia and policythemia vera: The missing piece in the puzzle of their increased cardiovascular risk?
Authors: Fabrizio Vianello, Giuseppe Cella, Elena Osto, Andrea Ballin, Giulia Famoso, Sara Tellatin, Sabino Iliceto, Umberto Cucchini, Graziella Saggiorato, Elisabetta Omenetto, Francesco Tona
Journal: American Journal of Hematology (2014)

Myeloproliferative neoplasms are most commonly associated with venous thrombosis. Up to 60% of patients experience a thrombotic event in their lifetimes, including stroke or myocardial infarction. It is unclear whether pathogenetic factors linking essential thrombocythemia (ET) and polycythemia vera (PV) to thrombotic complications do play a role in the risk of coronary artery disease (CAD). We aimed to assess coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic patients with ET and PV. Fifty-two patients with ET (M/F 13/39, age 61 ± 7 years) and 22 patients with PV (M/F 13/9, age 60.4 ± 13 years) without clinical evidence of heart disease, and 50 controls matched for age and gender were studied. None had CAD. All control subjects were asymptomatic with no history of heart disease. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. In patients with ET and PV, CFR was lower than in controls (2.9 ± 0.94 and 2.2 ± 0.7 vs. 3.8 ± 0.7, P < 0.004 and P < 0.0001 respectively). The prevalence of CFR ≤ 2.5 was higher in patients with ET (20 cases, 38.5%) and PV (15 cases, 68.2%) compared with controls (4.1%) (P < 0.0001). Severe CFR (CFR < 2) impairment was found in eight patients with ET (15.4%), in nine patients with PV (40.9%), and in none of control subjects. The mutation of JAK2 gene was associated with abnormal CFR. Asymptomatic patients with ET and PV have coronary microvascular dysfunction in the absence of clinical conditions suggesting CAD.
Human gamma interferon strongly upregulates its own gene expression in peripheral blood lymphocytes.
Authors: K J Hardy, T Sawada
Journal: The Journal of Experimental Medicine (1989)

The product of the human IFN-gamma gene was found to be a powerful upregulatory stimulus for its own gene expression in lectin-activated human PBMC. The INF-gamma autosuperinduction response was further enhanced by "priming" PBMC with IFN-gamma. Primed cells maximally upregulated their levels of IFN-gamma specific mRNA 4-fold faster and more than 20-fold higher than mock-stimulated cells. High mRNA levels persisted for several days after stimulation, and enhanced secretion of biologically active IFN-gamma paralleled the observed upregulation of gene expression. Producer cells demonstrating this response were found to be primarily localized to the rosette E- (leu 11+) fraction of PBMC and appear to be of the LGL/NK variety. Whether the autosuperinduction phenomenon occurs through direct or indirect effects of IFN-gamma on producer cells is still unclear. These results may be important both to an understanding of the pathogenesis of immune dysfunction and to the design of more effective immunotherapy.
Erythrocyte damage in mild and severe psoriasis
Authors: P. Rocha-Pereira, A. Santos-Silva, I. Rebelo, A. FigneiRedo, A. Quintanilha, F. Teixeira
Journal: British Journal of Dermatology (2004)

Background Psoriasis is a common chronic and recurrent inflammatory skin disorder. Oxygen metabolites and proteases released by activated inflammatory cells may induce oxidative and proteolytic damage to plasma constituents and red blood cells (RBCs). RBCs have a limited biosynthesis capacity and poor repair mechanisms. Objectives To study RBCs as a potential cumulative marker of oxidative and proteolytic stress in psoriasis, and as a marker of worsening of the disease. Methods The study was performed in 70 patients with mild or severe psoriasis and in 40 control individuals. We evaluated total and differential leucocyte count and, as markers of leucocyte activation, plasma elastase and lactoferrin. Besides the basic RBC study (RBC count, haematocrit, haemoglobin concentration and haematimetric indices) we evaluated antioxidant defences (catalase, superoxide dismutase, glutathione peroxidase and selenium), osmotic fragility and reticulocyte count; in the RBC membrane we evaluated lipid peroxidation and susceptibility to lipid peroxidation, membrane fluidity, levels of cholesterol and phospholipids, membrane‐bound haemoglobin, band 3 profile and levels of vitamin E; serum levels of bilirubin, total plasma antioxidant capacity, lipid profile and lipid peroxidation were also evaluated. Results Psoriasis patients showed a rise in leucocytes, mainly neutrophils, which was associated with a rise in elastase and lactoferrin. Patients had a reduced RBC count, antioxidant defences and membrane fluidity, elevated membrane lipid peroxidation, membrane‐bound haemoglobin, osmotic fragility and reticulocyte count, and a different band 3 profile. Most of these modifications were enhanced in severe psoriasis. Conclusions In summary, our data show that the RBCs are at a lower number in psoriasis patients, and present several changes denoting an enhanced damage and/or ageing process, which seem to be strongly connected with neutrophil activation, oxidative stress and worsening of psoriasis.
Effects of Proximal Gut Bypass on Glucose Tolerance and Insulin Sensitivity in Humans
Authors: Igal Breitman, James M. Isbell, Jabbar Saliba, Kareem Jabbour, Charles Robb Flynn, Pamela A. Marks-Shulman, Blandine Laferrère, Naji N. Abumrad, Robyn A. Tamboli
Journal: Diabetes Care (2013)

Roux-en-Y gastric bypass (RYGB) surgery produces a significant improvement in glucose metabolism prior to substantial weight loss; this is proposed to result from an enhanced incretin effect secondary to bypass of the duodenum and proximal jejunum. However, the caloric restriction that occurs early after surgery also has beneficial metabolic effects. To dissect the contribution of nutrient bypass of the proximal gut to improved glucose tolerance after RYGB surgery from caloric restriction, we induced a “non-surgical, proximal gut bypass” by directly administering a glucose load to the jejunum via a nasally inserted feeding tube.

We studied 10 obese participants (BMI = 41.3 ± 7.4 kg/m2; 36 ± 9 years; 60% female; HbA1c = 5.5 ± 0.5%) on two occasions. At each visit, a 50-g glucose load was administered to either the stomach or proximal jejunum in random order. Blood was sampled −10, 0, 2, 4, 6, 8, …
Differentiation antigens identify subpopulations of rabbit T and B lymphocytes. Definition by flow cytometry.
Authors: S Jackson, T M Chused, J M Wilkinson, W M Leiserson, T J Kindt
Journal: The Journal of Experimental Medicine (1983)

A panel of six monoclonal antibodies produced against cell surface glycoproteins of a rabbit T lymphocyte line was used with flow cytometry to define rabbit lymphocyte subpopulations. Four thymocyte populations were characterized by size and expression of cell surface antigens and appear to represent stages in thymocyte differentiation. Rabbit spleen contained five subpopulations: two of T lineage, two of B, and a null cell subset. Bimodal distribution of staining of thymocytes and peripheral T cells was observed using an antibody (9AE10) directed against a Thy-1 analogue in the rabbit, suggesting two separate T cell lineages. One of the monoclonal reagents, L11/135, reacted strongly with peripheral rabbit T cells as shown by two-color immunofluorescence. In functional studies, only the L11/135-bearing cells responded to the T cell mitogens concanavalin A and phytohemagglutinin and to allogeneic splenocytes. The thymocyte subpopulations and the peripheral T and B cell subsets differ from those described in mouse and man.
Assessment and Management of Hypertension in Transplant Patients
Authors: Matthew R. Weir, Ellen D. Burgess, James E. Cooper, Andrew Z. Fenves, David Goldsmith, Dianne McKay, Anita Mehrotra, Mark M. Mitsnefes, Domenic A. Sica, Sandra J. Taler
Journal: Journal of the American Society of Nephrology (2015)

Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients.