tbuckley/cabot-search huggingface dataset:
Relationship Between the Prognostic Expectations of Seriously Ill Patients Undergoing Hemodialysis and Their Nephrologists
Authors: Melissa W. Wachterman, Edward R. Marcantonio, Roger B. Davis, Robert A. Cohen, Sushrut S. Waikar, Russell S. Phillips, Ellen P. McCarthy
Journal: JAMA Internal Medicine (2013)

Patients undergoing hemodialysis have an annual mortality rate exceeding 20%, comparable to many types of cancer. Past research has shown that patients with cancer overestimate their likelihood of survival relative to their physicians, but this relationship has not been examined in patients with noncancer diagnoses. Perceptions of prognosis and transplant candidacy may influence goals of care.To compare the perceptions of hemodialysis patients and their nephrologists concerning prognosis and the likelihood of transplant; to follow actual survival; and to explore the relationship between patients' expectations and their goals of care.We completed a medical record abstraction to estimate 1-year mortality risk among patients who underwent dialysis at any time from November 1, 2010, through September 1, 2011. We then conducted in-person interviews with eligible patients whose predicted 1-year mortality, based on validated prognostic tools, was at least 20%. We also interviewed their nephrologists. We compared patients' and physicians' expectations about 1- and 5-year survival and transplant candidacy and measured the association between patients' expectations and goals of care. We then followed actual survival using Kaplan-Meier methods.Two dialysis units in Boston. Two hundred seven patients undergoing hemodialysis included in the medical record review, with 62 eligible patients interviewed.Predicted 1-year mortality risk using validated prognostic tools; actual survival; patients' and physicians' expectations about 1-year survival and likelihood of transplant; and patients' goals of care.Of the 207 hemodialysis patients, 72.5% had a predicted 1-year mortality of at least 20%. Of the 80 patients eligible for interview, 62 participated (response rate, 78%). Patients were significantly more optimistic than their nephrologists about 1- and 5-year survival (P < .001 for both) and were more likely to think they were transplant candidates (37 [66%] vs 22 [39%] [P = .008]). Of the 81% of patients reporting a 90% chance or greater of being alive at 1 year, 18 (44%) preferred care focused on extending life, even if it meant more discomfort, compared with 1 (9%) among patients reporting a lower chance of survival (P = .045). Actual survival was 93% at 1 year but decreased to 79% by 17 months and 56% by 23 months.Hemodialysis patients are more optimistic about prognosis and transplant candidacy than their nephrologists. In our sample, patients' expectations about 1-year survival were more accurate than those of their nephrologists, but their longer-term survival expectations dramatically overestimated even their 2-year survival rates. Patients' prognostic expectations are associated with their treatment preferences. Our findings suggest the need for interventions to help providers communicate effectively with patients about prognosis.
Efficacy and Safety of Monoclonal Antibody to Human Tumor Necrosis Factor α in Patients With Sepsis Syndrome
Authors: E Abraham, R Wunderink, H Silverman, T M Perl, S Nasraway, H Levy, R Bone, R P Wenzel, R Balk, R Allred
Journal: JAMA (1995)

To evaluate the efficacy and safety of anti-tumor necrosis factor alpha monoclonal antibody (TNF-alpha MAb) in the treatment of patients with sepsis syndrome.Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial.A total of 31 hospitals in the United States and Canada.There were 994 patients with sepsis syndrome enrolled in this clinical trial, and 971 patients were infused with the study drug.Patients were prospectively stratified into shock or nonshock groups and then randomized to receive a single infusion of 15 mg/kg of TNF-alpha MAb, 7.5 mg/kg of TNF-alpha MAb, or placebo. Patients received standard aggressive medical and surgical care during the 28-day postinfusion period.Twenty-eight-day all-cause mortality.The distribution of variables describing demographics, organ system dysfunction or failure, preinfusion Acute Physiology and Chronic Health Evaluation II score, number of organs failing at baseline, initial sites of infection, infecting microorganisms, antimicrobials used, and initial invasive procedures was similar among patients in the TNF-alpha MAb and placebo treatment arms. Among all infused patients, there was no difference in all-cause mortality in patients who received placebo as compared with those who received TNF-alpha MAb. In septic patients with shock (n = 478), there was a trend toward a reduction in all-cause mortality, which was most evident 3 days after infusion: 25 of 162 patients treated with 15 mg/kg of TNF-alpha MAb died, 22 of 156 patients treated with 7.5 mg/kg of TNF-alpha MAb died, and 44 of 160 patients in the placebo group died (15 mg/kg: 44% reduction vs placebo, P = .01; 7.5 mg/kg: 48.7% reduction vs placebo, P = .004). At day 28, the reduction in mortality for shock patients was not significant for either dose of TNF-alpha MAb relative to placebo (15 mg/kg, 61 deaths among 162 patients [37.7% mortality]; 7.5 mg/kg, 59 deaths among 156 patients [37.8% mortality]; placebo, 73 deaths among 160 patients [45.6% mortality]; P = .20 for 7.5 mg/kg and P = .15 for 15 mg/kg). Serious adverse events were reported in 4.6% of all infused patients. No immediate hypersensitivity allergic reactions due to TNF-alpha MAb were reported. Serum sickness-like reactions were seen in 2.5% of patients receiving TNF-alpha MAb.There was no decrease in mortality between placebo and TNF-alpha MAb in all infused patients. In septic shock patients who received TNF-alpha MAb, a significant reduction in mortality was present 3 days after infusion. Although a trend toward reduced mortality continued at 28 days following treatment with TNF-alpha MAb, the difference in mortality among shock patients treated with placebo or TNF-alpha MAb was not significant.
Sarcoidosis and granuloma genes: a family-based study in African-Americans
Authors: B.A. Rybicki, M.J. Maliarik, L.M. Poisson, M.C. Iannuzzi
Journal: European Respiratory Journal (2004)

The evidence for a genetic component in the aetiology of sarcoidosis includes familial aggregation, associations with genetic polymorphisms, and linkage to the major histocompatibility complex class region on chromosome 6p. Unfortunately, the majority of genetic associations with sarcoidosis have not been consistently replicated. In the present study, using a family-based study design, which controls for population stratification, the authors attempted to replicate previously reported associations between sarcoidosis and three attractive candidate genes studied primarily in case-control samples. In 225 nuclear families, ascertained through African Americans with a history of sarcoidosis, no evidence was found for an association between sarcoidosis susceptibility and polymorphisms in the angiotensin converting enzyme, vitamin D receptor and tumour necrosis factor‐α genes. Further analyses of chronic and acute disease phenotypes failed to reveal any notable associations. Assuming an underlying inheritance model with an additive allelic effect on disease risk, the current study had ∼80–90% statistical power to detect a 3‐fold increased risk associated with the putative risk allele of the polymorphisms under study. The present authors conclude that in African-Americans, the angiotensin converting enzyme, vitamin D receptor, and tumour necrosis factor‐α genes are not significant risk factors for sarcoidosis susceptibility.
The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA
Authors: Richard F. Schlenk, Erdogan Taskesen, Yvette van Norden, Jürgen Krauter, Arnold Ganser, Lars Bullinger, Verena I. Gaidzik, Peter Paschka, Andrea Corbacioglu, Gudrun Göhring, Andrea Kündgen, Gerhard Held, Katharina Götze, Edo Vellenga, Juergen Kuball, Urs Schanz, Jakob Passweg, Thomas Pabst, Johan Maertens, Gert J. Ossenkoppele, Ruud Delwel, Hartmut Döhner, Jan J. Cornelissen, Konstanze Döhner, Bob Löwenberg
Journal: Blood (2013)
Major Depression in Elderly Home Health Care Patients
Authors: Martha L. Bruce, Gail J. McAvay, Patrick J. Raue, Ellen L. Brown, Barnett S. Meyers, Denis J. Keohane, David R. Jagoda, Carol Weber
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Despite the growth of geriatric home health services, little is known about the mental health needs of geriatric patients seen in their homes. The authors report the distribution, correlates, and treatment status of DSM-IV major depression in a random sample of elderly patients receiving home health care for medical or surgical problems. METHOD: Geriatric patients newly admitted to a large, traditional visiting nurse agency were sampled on a weekly basis over a period of 2 years. The 539 patients ranged in age from 65 to 102 years; 351 (65%) were women, and 81 (15%) were nonwhite. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to interview patients and informants. The authors reviewed the results of these interviews plus the patients' medical charts to generate a best-estimate DSM-IV psychiatric diagnosis. RESULTS: The patients had substantial medical burden and disability. According to DSM-IV criteria, 73 (13.5%) of the 539 patients were diagnosed with major depression. Most of these patients (N=52, 71%) were experiencing their first episode of depression, and the episode had lasted for more than 2 months in most patients (N=57, 78%). Major depression was significantly associated with medical morbidity, instrumental activities of daily living disability, reported pain, and a past history of depression but not with cognitive function or sociodemographic factors. Only 16 (22%) of the depressed patients were receiving antidepressant treatment, and none was receiving psychotherapy. Five (31%) of the 16 patients receiving antidepressants were prescribed subtherapeutic doses, and two (18%) of the 11 who were prescribed appropriate doses reported not complying with their antidepressant treatment. CONCLUSIONS: Geriatric major depression is twice as common in patients receiving home care as in those receiving primary care. Most depressions in patients receiving home care are untreated. The poor medical and functional status of these patients and the complex organizational structure of home health care pose a challenge for determining safe and effective strategies for treating depressed elderly home care patients.
Gonadotropin-Releasing Hormone Induces Apoptosis of Prostate Cancer Cells
Authors: Sarah Kraus, Gal Levy, Tamar Hanoch, Zvi Naor, Rony Seger
Journal: Cancer Research (2004)

Abstract A standard therapy used today for prostate cancer is androgen ablation by gonadotropin-releasing hormone analogs (GnRH-a). Although most patients respond to androgen ablation as an initial systemic therapy, nearly all cases will develop androgen resistance, the management of which is still a major challenge. Here, we report that GnRH-a can directly induce apoptosis of the androgen-independent prostate cancer-derived DU145 and PC3 cell lines. Using specific inhibitors, we found that the apoptotic effect of GnRH-a is mediated by c-Jun NH2-terminal kinase (JNK) and inhibited by the phosphatidylinositol 3′-kinase (PI3K)-protein kinase B (PKB) pathway. Indeed, in DU145 cells, GnRH-a activates the JNK cascade in a c-Src- and MLK3-dependent manner but does not involve protein kinase C and epidermal growth factor receptor. Concomitantly, GnRH-a reduces the activity of the PI3K-PKB pathway, which results in the dephosphorylation of PKB mainly in the nucleus. The reduction of PKB activity releases PKB-induced inhibition of MLK3 and thus further stimulates JNK activity and accelerates the apoptotic effect of GnRH-a. Interestingly, extracellular signal-regulated kinase is also activated by GnRH-a, and this occurs via a pathway that involves matrix metalloproteinases and epidermal growth factor receptor, but its activation does not affect JNK activation and the GnRH-a-induced apoptosis. Our results support a potential use of GnRH-a for the treatment of advanced prostate cancer and suggest that the outcome of this treatment can be amplified by using PI3K-PKB inhibitors.
The impact of the addition of omalizumab on the utilization of healthcare resources by severe persistent asthma patients
Authors: Sarah Dyer, Stuart Packham, Sarah Davies
Journal: European Respiratory Journal (2013)

Aim: To study the impact of the addition of Omalizumab to the treatment regime of patients with severe asthma, on their utilization of healthcare resources over a two year period.  Method: All patients were started on Omalizumab for severe persistent asthma in accordance with licenced indications and dosed at 2 or 4 weekly intervals dependent on their weight and IgE levels. Data on all patients in our unit receiving Omalizumab were analysed comparing hospital admissions, bed days,and Emergency Department (A+E) attendances in the 2 years pre and post commencement of Omalizumab as well as Quality of life using the Asthma Control Test (ACT) and the Asthma Quality of Life Questionaire (AQLQ) and whether use of oral prednisolone was able to be reduced.  Results: 11 patients (1 male) were studied with a mean age of 44 (SD 8.5). Number of admissions reduced from 38 in the two years prior to the commencement of Omalizumab to 9 in the two years afterwards, 205 bed-days pre to 31 post and 19 attendances at the Emergency Department (A+E) pre to 9 post. Three patients on maintenance steroids were able to stop steroids and mean daily steroid dosage of the cohort reduced from 9.8 mg/day to 4.7 mg/day. Quality of life improved significantly; ACT from 6.5 pre Omalizumab to 16.3 post and AQLQ from 2.4 to 4.8.  Conclusion: The addition of Omalizumab to patients with severe persistent asthma on maximal therapy resulted in significant sustained reductions in healthcare utilization over a two year period and improvements in quality of life.
Varicose Ulcers and Eczema
Authors: A. D. Wright
Journal: BMJ (1940)

Varicose veins, though sometimes practically symptom- less, often produce very definite symptoms such as real pain in the veins themselves, accentuated by either strenuous exercise or long standing.Itching, tiredness, and fullness in the legs towards the end of the day are complained of, as well as severe muscular cramps on exercise, especially when swimming ; these cramps may be very severe at night after a strenuous day, and muscular soreness persists for forty-eight hours.So frequent are muscular cramps that in Germany varicose veins are known as "Krampfader."Apart from the relief of these symptoms patients come for treatment of the varicose veins when complications develop.In this connexion it is most essential to note that these complications are not new diseases but further manifestations of the disordered circulation in the leg that produces a loss of balance between arterial inflow and venous outflow.This loss of equilibrium leads to loading of the tissues with oedema and katabolites, and as a result the normal mechanism of resistance to trauma and infection breaks down.Circulatory equilibrium must therefore be restored by treatment of the varicose veins, and by supportive treatment if the deep veins are also at fault.Once the circulation is put right and the leg remains free from oedema the ulcers and eczema will heal without the help of cod-liver oil, insulin dressings, healing rays, and a hundred and one other much-recom- mended local applications which consume time and money.The main complications of varicose veins are thrombo- phlebitis, eczema, and ulceration, but in long-standing cases all the tissues of the leg suffer from the disordered circulation: the bones show periostitis and osteoporosis, the joints hypertrophic osteo-arthritis ; the fascia and septa may ossify or calcify, and the muscles develop a peculiar hypertrophy comparable probably to the unhealthy cardiac hypertrophy in myocarditis.Pes planus arises in many cases, and with the development of painful ulcers the foot may become deformed from reflex muscular contractions.
Hyperthermic Intraperitoneal Chemoperfusion in Combined Treatment of Local-Advanced and Peritoneal Disseminated Gastric Cancer
Authors: Yarema Roman, Fetsych Taras, Ohorchak Myron, Zubarev Gennadiy, Mylyan Yuriy, Oliynyk Yuriy, Matusyak Myron, Zubarev Mykola, Gyrya Petro, Kovalchuk Yuriy, Safiyan Victor, Semotuk Taras, Novicka Tetyana, Laba Lubov, Yarysh Maryana
Journal: Annals of Oncology (2014)
Effect of adenosine on atrioventricular conduction. I: Site and characterization of adenosine action in the guinea pig atrioventricular node.
Authors: H F Clemo, L Belardinelli
Journal: Circulation Research (1986)

Adenosine has a negative dromotropic effect and modulates hypoxia-induced atrioventricular (AV) conduction delay. To further characterize the negative dromotropic effect of adenosine in the guinea pig heart, we determined the site of adenosine-induced AV conduction block; the effect of uptake and deamination of adenosine on its concentration-negative dromotropic effect, and the adenosine receptor that mediates this action. In isolated AV node preparations (n = 16), adenosine in a dose-dependent manner decreased significantly the duration and amplitude of the action potential of atrionodal and nodal cells and, in addition, markedly depressed the maximum rate of rise of the action potential of nodal cells. At high concentrations (greater than 20 microM), adenosine rendered nodal cells inexcitable. In isolated perfused hearts (n = 7), adenosine (5.7 microM) prolonged total AV conduction time by 21 +/- 2 msec. Of this prolongation, 83% was due to an increase in the nodal-to-His-bundle interval and the remaining 17% to an increase in the atrionodal to nodal interval. Infusion of adenosine to cause a 50% increase (EC50) in atria-to-His bundle (AH) interval prolongation resulted in a perfusate (arterial) adenosine concentration of 5.0 +/- 0.6 microM and effluent (venous) adenosine concentrations of 2.8 +/- 0.4 microM, i.e., an arteriovenous difference of 44% (n = 4). When adenosine uptake and deamination were inhibited with dipyridamole (0.5 microM) plus erythro-9-(2-hydroxy-3-nonyl)adenine (5 microM), respectively, the EC50s were 0.28 +/- 0.02 (perfusate) and 0.32 +/- 0.03 microM (effluent). These data indicate that when nucleoside metabolism is inhibited, arterial and venous concentrations of adenosine reach equilibrium. In an additional 10 hearts, the following rank order of potency of adenosine agonists in causing AH interval prolongation was found: N6-cyclopentyladenosine greater than N6-(L-2-phenyl-isopropyl)adenosine greater than 5'-N-ethylcarboxyamidoadenosine greater than or equal to 2-chloroadenosine greater than adenosine, which is compatible with activation of an A1-type receptor. In summary: the site of adenosine-induced AV conduction block is the nodal zone of the AV node, when adenosine uptake and deamination are inhibited, adenosine in concentrations similar to that released by hypoxia causes significant AH interval prolongation, and the adenosine receptor mediating the negative dromotropic effect of adenosine is of the A1-type.
Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis
Authors: T. Schön, D. Elias, F. Moges, E. Melese, T. Tessema, O. Stendahl, S. Britton, T. Sundqvist
Journal: European Respiratory Journal (2003)

Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal NO production, would improve the clinical outcome of TB by increasing NO production. In a randomised double-blind study, patients with smear-positive TB (n=120) were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. Primary outcomes were sputum conversion, weight gain, and clinical symptoms after week 8. Secondary outcomes were sedimentation rate and levels of NO metabolites, arginine, citrulline, and tumour necrosis factor‐α. Compared with the human immunodeficiency virus (HIV)−/TB+ placebo group, the HIV−/TB+ patients in the arginine group showed significant improvement, defined as increased weight gain, higher sputum conversion rate and faster reduction of symptoms, such as cough. The arginine level increased after week 2 in the HIV−/TB+ arginine group (100.2 µM (range 90.5–109.9) <i>versus</i> 142.1 µM (range 114.1–170.1)) compared with the HIV−/TB+ placebo group (105.5 µM (range 93.7–117.3) <i>versus</i> 95.7 µM (range 82.4–108.9)). HIV seroprevalence was 52.5%. No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo. Arginine is beneficial as an adjuvant treatment in human immunodeficiency virus-negative patients with active tuberculosis, most likely mediated by increased production of nitric oxide.
Regulation of Cytokine Signaling by B Cell Antigen Receptor and Cd40-Controlled Expression of Heparan Sulfate Proteoglycans
Authors: Robbert van der Voort, Robert M.J. Keehnen, Esther A. Beuling, Marcel Spaargaren, Steven T. Pals
Journal: The Journal of Experimental Medicine (2000)

Recently, biochemical, cell biological, and genetic studies have converged to reveal that integral membrane heparan sulfate proteoglycans (HSPGs) are critical regulators of growth and differentiation of epithelial and connective tissues. As a large number of cytokines involved in lymphoid tissue homeostasis or inflammation contain potential HS-binding domains, HSPGs presumably also play important roles in the regulation of the immune response. In this report, we explored the expression, regulation, and function of HSPGs on B lymphocytes. We demonstrate that activation of the B cell antigen receptor (BCR) and/or CD40 induces a strong transient expression of HSPGs on human tonsillar B cells. By means of these HSPGs, the activated B cells can bind hepatocyte growth factor (HGF), a cytokine that regulates integrin-mediated B cell adhesion and migration. This interaction with HGF is highly selective since the HSPGs did not bind the chemokine stromal cell–derived factor (SDF)-1α, even though the affinities of HGF and SDF-1α for heparin are similar. On the activated B cells, we observed induction of a specific HSPG isoform of CD44 (CD44-HS), but not of other HSPGs such as syndecans or glypican-1. Interestingly, the expression of CD44-HS on B cells strongly promotes HGF-induced signaling, resulting in an HS-dependent enhanced phosphorylation of Met, the receptor tyrosine kinase for HGF, as well as downstream signaling molecules including Grb2-associated binder 1 (Gab1) and Akt/protein kinase B (PKB). Our results demonstrate that the BCR and CD40 control the expression of HSPGs, specifically CD44-HS. These HSPGs act as functional coreceptors that selectively promote cytokine signaling in B cells, suggesting a dynamic role for HSPGs in antigen-specific B cell differentiation.