tbuckley/cabot-search huggingface dataset:
Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes
Authors: M Carol, A Lambrechts, A Van Gossum, M Libin, M Goldman, F Mascart-Lemone
Journal: Gut (1998)

Background —Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses. Aims —To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation. Patients —Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa. Methods —Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT). Results —The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4 + cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4. Conclusions —Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.
Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder
Authors: Ewgeni Jakubovski, Anjali L. Varigonda, Nicholas Freemantle, Matthew J. Taylor, Michael H. Bloch
Journal: American Journal of Psychiatry (2015)

Objective: Previous studies suggested that the treatment response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder follows a flat response curve within the therapeutic dose range. The present study was designed to clarify the relationship between dosage and treatment response in major depressive disorder. Method: The authors searched PubMed for randomized placebo-controlled trials examining the efficacy of SSRIs for treating adults with major depressive disorder. Trials were also required to assess improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses. The longitudinal data were analyzed with a mixed-regression model. Endpoint and tolerability analyses were analyzed using meta-regression and stratified subgroup analysis by predefined SSRI dose categories in order to assess the effect of SSRI dosing on the efficacy and tolerability of SSRIs for major depressive disorder. Results: Forty studies involving 10,039 participants were included. Longitudinal modeling (dose-by-time interaction=0.0007, 95% CI=0.0001–0.0013) and endpoint analysis (meta-regression: β=0.00053, 95% CI=0.00018–0.00088, z=2.98) demonstrated a small but statistically significant positive association between SSRI dose and efficacy. Higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects (meta-regression: β=0.00207, 95% CI=0.00071–0.00342, z=2.98) and decreased likelihood of all-cause dropout (meta-regression: β=–0.00093, 95% CI=–0.00165 to −0.00021, z=−2.54). Conclusions: Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses.
Colchicine Treatment for Recurrent Pericarditis
Authors: Y. Adler, Y. Finkelstein, J. Guindo, A. Rodriguez de la Serna, Y. Shoenfeld, A. Bayes-Genis, A. Sagie, A. Bayes de Luna, D. H. Spodick
Journal: Circulation (1998)

Background —The most troublesome complication of acute pericarditis is recurrent episodes of pericardial inflammation, occurring in 15% to 32% of cases. The cause of the recurrence is usually unknown, although in some cases it may be traced to viral infection or may be a consequence of coronary artery bypass grafting. The optimal method for prevention has not been fully established; accepted modalities include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents, and pericardiectomy. Methods and Results —Based on the proven efficacy of colchicine therapy for familial Mediterranean fever (recurrent polyserositis), several small studies have used colchicine successfully to prevent recurrence of acute pericarditis after failure of conventional treatment. Recently, we reported the results from the largest multicenter international study on 51 patients who were treated with colchicine to prevent further relapses and who were followed up for ≤10 years. Conclusions —In light of new trial data that have accumulated in the past decade, we review the evidence for the efficacy and safety of colchicine for the prevention of recurrent episodes of pericarditis. Clinical and personal experience shows that colchicine may be an extremely promising adjunct to conventional treatment and may ultimately serve as the initial mode of treatment, especially in idiopathic cases.
Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial
Authors: Nancy S Padian, Ariane van der Straten, Gita Ramjee, Tsungai Chipato, Guy de Bruyn, Kelly Blanchard, Stephen Shiboski, Elizabeth T Montgomery, Heidi Fancher, Helen Cheng, Michael Rosenblum, Mark van der Laan, Nicholas Jewell, James McIntyre
Journal: The Lancet (2007)
Big Bang in the Evolution of Extant Malaria Parasites
Authors: T. Hayakawa, R. Culleton, H. Otani, T. Horii, K. Tanabe
Journal: Molecular Biology and Evolution (2008)

Malaria parasites (genus Plasmodium) infect all classes of terrestrial vertebrates and display host specificity in their infections. It is therefore assumed that malaria parasites coevolved intimately with their hosts. Here, we propose a novel scenario of malaria parasite-host coevolution. A phylogenetic tree constructed using the malaria parasite mitochondrial genome reveals that the extant primate, rodent, bird, and reptile parasite lineages rapidly diverged from a common ancestor during an evolutionary short time period. This rapid diversification occurred long after the establishment of the primate, rodent, bird, and reptile host lineages, which implies that host-switch events contributed to the rapid diversification of extant malaria parasite lineages. Interestingly, the rapid diversification coincides with the radiation of the mammalian genera, suggesting that adaptive radiation to new mammalian hosts triggered the rapid diversification of extant malaria parasite lineages.
Designing trials of interventions to change professional practice in primary care: lessons from an exploratory study of two change strategies
Authors: S. Rogers
Journal: BMJ (2000)

<b>INTRODUCTION:</b> With the objective of reducing the rate of readmissions of discharged for COPD exacerbation, our chronic outpatient respiratory care unit (UCCRA) was created. <b>METHODS:</b> Observational study in which we compared data of patient included in UCCRA from January to October 2015 with patients with not home care, and with the patients included in UCCRA in the same period in 2014 with only telephone follow-up. Patients were admitted in UCCRA if they fit our criteria, based on our Readmission Risk Scale (RRS) that incorporates these variables: age, exacerbations (hospitalization or not) in the last year, FEV1, bacterial colonization, chronic bronchitis, Karnofsky index and cardiovascular comorbidity. Patients were included in UCCRA if they had suffered &gt; 2 hospitalizations in the last year or &gt; 7 points in our RRS. <b>RESULTS:</b> We included 399 patients, 234 patients were discharged after an exacerbation of COPD in 2015, with a mean age (MA) of 71.8 years, mean stay (MS) of 7.4 days and 13.3% of readmissions. 108 were included in UCCRA, who had significantly higher MS and previous exacerbations, reduced FEV1 and Karnofsky, and higher percentage of readmissions than not included (22.2 vs 6.3%). Patients with home care in 2015, compared with 2014 with telephone follow-up (165 patients, MA: 72.6, MS: 6.2), had more previous non-hospital exacerbations (p &lt;0.05) and less readmissions (13.6 vs 19.3%, p 0.06). UCCRA patients in 2015 had significantly less previous hospitalizations and fewer readmissions than those of UCCRA in 2014 (22.2 vs 50%). <b>CONCLUSIONS:</b> UCCRA with home care was valid to reduce readmissions in COPD patients, compared with telephone follow-up. Previous hospitalizations was the variable that better predict readmission.
How Does Treatment Satisfaction Work?
Authors: Mark Peyrot, Richard R. Rubin
Journal: Diabetes Care (2009)

OBJECTIVE This study tested a model hypothesizing that treatment affects objective clinical outcomes, which in turn affect perceived consequences, which in turn affect satisfaction and preference judgments. RESEARCH DESIGN AND METHODS The model was tested in a double-blind, randomized clinical trial in which 266 patients with type 1 diabetes added active or placebo pramlintide to their insulin regimens. Objective clinical outcomes included changes in glucose and weight control, insulin requirements, incidence of hypoglycemia, and study drug tolerance. At the end of the trial, patients completed the validated PRAM-TSQ questionnaire measuring treatment satisfaction and preference and perceived medication benefits and side effects. RESULTS Statistical modeling demonstrated that active pramlintide was significantly associated with greater treatment satisfaction, preference, and perceived benefits (all except hypoglycemia prevention), as well as objective clinical outcomes (weight loss, lower postprandial glucose [PPG], lower medication tolerance, more hypoglycemia). Perceptions of treatment consequences were sensitive and specific to their cognate objective clinical outcomes (no halo effects). Clinical outcomes (especially PPG) accounted for almost half of the effect of the study medication on treatment satisfaction and preference. Treatment satisfaction and preference were strongly related to the perceived benefits/side effects of the study medication, and these perceptions (especially glucose control) mediated most of the association of clinical outcomes with satisfaction and preference. CONCLUSIONS This model received substantial empirical support. Improvements in objective clinical outcomes accounted for a large part of the association of pramlintide treatment with higher treatment satisfaction and preference. Perceived treatment consequences mediated the effect of objective clinical benefits on satisfaction with and preference for the study medication.
Abstract 13004: Decreased Respiratory Variation of Hepatic Vein Doppler Predicts Major Clinical Outcomes in Fontan Patients
Authors: Makoto Mori, Kayoko Shioda, Maan Jokhadar, Robert W Elder, Nancy McCabe, Camden Hebson, Brian E Kogon, Anurag Sahu, Frederick Rodriguez, Michael McConnell, Wendy M Book
Journal: Circulation (2014)

Introduction:  Pulmonary blood flow in the Fontan circulation is dependent on respiratory effort due to the lack of a subpulmonic ventricle. Respiratory variation in hepatic vein (HV) flow measured by the Doppler has been described in Fontan patients as a surrogate of respiratory variation of pulmonary blood flow. Whether clinical outcomes are predicted by the degree of respiratory variation of the flow in Fontan patients is unknown.   Hypothesis:  Reduced respiratory variation in forward HV flow is associated with adverse clinical outcomes.   Methods:  We performed a retrospective review of 104 adult Fontan patients who had echocardiograms between 2004 and 2014. HV Doppler data included peak inspiratory and expiratory velocity time integral (VTI) of forward and retrograde flow during cardiac cycles in inspiration and expiration. The relationship between respiratory variation of HV Doppler measurements and major adverse events (death or transplantation) was examined using survival analysis.   Results:  104 post-Fontan patients (73% systemic LV, 42% atriopulmonary (APC) Fontan, mean age 28.4 ± 7.6 years, mean time from Fontan 21.7 ± 5.4 years) were analyzed. The mean difference between inspiratory and expiratory HV forward VTI was 8.4 ± 2.2cm and percent difference of HV forward VTI 61.9 ± 26.3%. 16 patients (5 APC, 11 lateral-tunnel) had HV forward VTI percent difference ≥ 90%, suggesting an inspiration-dependent venous flow independent of Fontan type (p = 0.69). 20 major adverse events occurred: 12 deaths, 8 transplants. After adjusting for potential confounders including body surface area, reduced respiratory variation in forward VTI was significantly associated with events: Compared to the middle tertile of difference in HV forward flow between inspiration and expiration, the lowest tertile had an estimated hazard ratio of 18.0 [95% CI 1.65-195.5, p=0.018] for adverse events.   Conclusions:  Reduced respiratory variation in forward HV flow was predictive of death or transplantation in this cohort of Fontan patients. A subset (15%) had forward HV flow only during inspiration, independent of Fontan type. Additional studies are needed to establish further clinical significance and reproducibility of the HV Doppler parameters.
SPLENECTOMY AND KARYOTYPIC CONVERSION IN CHRONIC MYELOID LEUKÆMIA
Authors: G. Mathé, L. Schwarzenberg, A.M. Vénuat, C. Rosenfeld, C. Jasmin, P. Ribaud, M. Musset, J.L. Misset, D. Machover, F. De Vassal, M. Hayat
Journal: The Lancet (1979)
Twenty two year survival after incomplete resection of advanced adenoid cystic bronchogenic carcinoma
Authors: N. Schoenfeld, W. Rahn, R. Loddenkemper
Journal: European Respiratory Journal (1996)

In 1972, a 42 year old patient underwent thoracotomy for adenoid cystic carcinoma of the left main-stem bronchus. Pneumonectomy was performed, but the resection was not complete as the tumour had invaded the aortic and tracheal wall. The patient did not receive postoperative radiotherapy. In 1993, the patient was readmitted with severe respiratory insufficiency due to complete endobronchial tumour obstruction of the intermediate bronchus and extensive tumour growth in the mediastinum. Endobronchial laser treatment followed by stent implantation led to immediate symptomatic relief. The tumour then responded well to combined endobronchial and percutaneous radiotherapy. The patient died 7 months after readmission from ileus due to pancreatitis. We conclude that patients with advanced adenoid cystic carcinoma may profit from palliative surgery with respect not only to symptoms but also to duration of life.
Unintentional percutaneous aspiration of a pleural hydatid cyst.
Authors: M A al Karawi, A R Mohamed, B O el Tayeb, M I Yasawy
Journal: Thorax (1991)

A Saudi man underwent repeated percutaneous aspiration of a pleural effusion before a pleural biopsy showed hydatid disease. Subsequent investigations confirmed hydatid disease in the pleura and liver. The patient underwent surgical evacuation and irrigation of the pleural cavity followed by medical treatment for the liver cyst with albendazole, with complete recovery and disappearance of the liver cyst.
Pattern of Prostate-Specific Antigen (PSA) Failure Dictates the Probability of a Positive Bone Scan in Patients With an Increasing PSA After Radical Prostatectomy
Authors: Zohar A Dotan, Fernando J. Bianco, Farhang Rabbani, James A. Eastham, Paul Fearn, Howard I. Scher, Kevin W. Kelly, Hui-Ni Chen, Heiko Schöder, Hedvig Hricak, Peter T. Scardino, Michael W. Kattan
Journal: Journal of Clinical Oncology (2005)

Physicians often order periodic bone scans (BS) to check for metastases in patients with an increasing prostate-specific antigen (PSA; biochemical recurrence [BCR]) after radical prostatectomy (RP), but most scans are negative. We studied patient characteristics to build a predictive model for a positive scan.From our prostate cancer database we identified all patients with detectable PSA after RP. We analyzed the following features at the time of each bone scan for association with a positive BS: preoperative PSA, time to BCR, pathologic findings of the RP, PSA before the BS (trigger PSA), PSA kinetics (PSA doubling time, PSA slope, and PSA velocity), and time from BCR to BS. The results were incorporated into a predictive model.There were 414 BS performed in 239 patients with BCR and no history of androgen deprivation therapy. Only 60 (14.5%) were positive for metastases. In univariate analysis, preoperative PSA (P = .04), seminal vesicle invasion (P = .02), PSA velocity (P < .001), and trigger PSA (P < .001) predicted a positive BS. In multivariate analysis, only PSA slope (odds ratio [OR], 2.71; P = .03), PSA velocity (OR, 0.93; P = .003), and trigger PSA (OR, 1.022; P < .001) predicted a positive BS. A nomogram for predicting the bone scan result was constructed with an overfit-corrected concordance index of 0.93.Trigger PSA, PSA velocity, and slope were associated with a positive BS. A highly discriminating nomogram can be used to select patients according to their risk for a positive scan. Omitting scans in low-risk patients could reduce substantially the number of scans ordered.
Caspase Regulation in Non–Small Cell Lung Cancer and its Potential for Therapeutic Exploitation
Authors: Dean A. Fennell
Journal: Clinical Cancer Research (2005)

Abstract Metastatic non–small cell lung cancer (NSCLC, stages IIIB/IV) is one of the most common and rapidly lethal causes of cancer related mortality worldwide. Efficacy of chemotherapy, the mainstay of treatment, is limited due to resistance in the vast majority of patients. NSCLC cells exhibit intrinsic apoptosis resistance. Understanding the molecular basis of this phenotype is critical, if therapy is to move beyond the therapeutic plateau that has been reached with conventional chemotherapy. Caspases occupy a pivotal position in the final common pathway of apoptosis. Increasing evidence suggests that these proteases are constitutively inhibited in NSCLC. This review discusses current knowledge relating to caspase regulation in NSCLC and highlights novel strategies for reversing the apoptosis resistant phenotype, with potential to accelerate development of effective therapy.
Beneficial response to anakinra and thalidomide in Schnitzler's syndrome
Authors: H D de Koning
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Schnitzler's syndrome is an inflammatory disorder characterised by chronic urticarial rash and monoclonal gammopathy, accompanied by periodic fever, arthralgia or arthritis, and bone pain. The cause and treatment are still unknown. <b>Objective:</b> To assess treatment with thalidomide and an interleukin 1 receptor antagonist, anakinra, in Schnitzler's syndrome. <b>Case reports:</b> Three patients with Schnitzler's syndrome are described, one with IgM gammopathy, two with IgG type. In one patient, thalidomide induced complete remission, but was stopped because of polyneuropathy. Anakinra 100 mg daily in all three patients led to disappearance of fever and skin lesions within 24 hours. After a follow up of 6–18 months, all patients are free of symptoms. <b>Conclusion:</b> Anakinra proved to be effective in three patients with Schnitzler's syndrome. This treatment is preferable to thalidomide, which induced a complete remission in one of our patients, as it has fewer side effects.
High-density lipoproteins inhibit urate crystal-induced inflammation in mice
Authors: Anna Scanu, Roberto Luisetto, Francesca Oliviero, Lyssia Gruaz, Paolo Sfriso, Danielle Burger, Leonardo Punzi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate the effects and mechanisms of action of high-density lipoproteins (HDL) in monosodium urate (MSU) crystal-induced inflammation —that is, gouty inflammation, in vivo. <h3>Methods</h3> Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL)-1 receptor antagonist (IL-1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer and May–Grünwald–Giemsa staining. The cytokine production and expression in the pouch were measured by ELISA and quantitative RT-PCR. <h3>Results</h3> MSU crystals induced leucocyte infiltration, mostly neutrophils, and the release of IL-1β, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 2 (CCL2) and IL-1Ra in pouch fluids. TNF remained under the detection limit. MSU crystals triggered IL-1β, IL-6 and CXCL1 expression in both pouch exudates and membranes, whereas CCL2 and TNF mRNA were not modulated. The co-injection of MSU crystals and HDL inhibited leucocyte influx by 59% and neutrophil infiltration by 83% and, in turn, both protein and mRNA levels of all assessed proinflammatory cytokines were reduced, but not those of IL-1Ra. Similar results were obtained when mice were injected with MSU crystals pretreated with HDL or TNF instead of crystals. When HDL and IL-1Ra were added together they displayed additional inhibition, suggesting different mechanisms of action. <h3>Conclusions</h3> This study demonstrated that HDL may represent an important factor in the modulation of gouty inflammation by acting on both tissue and infiltrating cells —that is, synovial tissue and synovial fluid cells. HDL display anti-inflammatory activity, in part, by interacting with crystals but also by directly acting on cells.
A Phase I and Pharmacokinetic Study of Weekly Paclitaxel and Carboplatin in Patients with Metastatic Esophageal Cancer
Authors: Marco B. Polee, Alex Sparreboom, Ferry A. L. M. Eskens, Ronald Hoekstra, Jacqueline van de Schaaf, Jaap Verweij, Gerrit Stoter, Ate van der Gaast
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To determine the maximum-tolerated dose, toxicity profile, and pharmacokinetics of a fixed dose of paclitaxel followed by increasing doses of carboplatin, given weekly to patients with advanced esophageal or gastric junction cancer. Experimental Design: Paclitaxel was administered on day 1 as a 1-h infusion at a fixed dose of 100 mg/m2 followed by a 1-h infusion of carboplatin targeting an area under the curve (AUC) of 2–5 mg × min/ml, with cycles repeated on days 8, 15, 29, 36, and 43. Results: Forty patients [36 males; median (range) age, 57 (40–74) years] were enrolled. Dose-limiting toxicity was observed at a carboplatin AUC of 5 mg × min/ml and consisted of treatment delay attributable to myelosuppression. No grade 3/4 treatment-related nonhematological toxicity was observed. The highest dose intensity (&amp;gt;95% of the planned dose over time) was achieved with a carboplatin AUC of 4 mg × min/ml. The mean (±SD) AUCs of unbound (Cu) and total paclitaxel were 0.662 ± 0.186 and 7.37 ± 1.33 μm × h, respectively. Clearance of Cu was 188 ± 44.6 liter/h/m2, which is not significantly different from historical data (P = 0.52). Cremophor EL clearance was 123 ± 23 ml/h/m2, similar to previous findings. Of 37 patients evaluable for response, 1 had complete response, 19 had partial response, and 10 had stable disease, accounting for an overall response rate of 54%. Conclusions: This regimen is very tolerable and effective, and the recommended doses for additional studies are paclitaxel (100 mg/m2), with carboplatin targeting an AUC of 4 mg × min/ml.