tbuckley/cabot-search huggingface dataset:
Impact of Bleomycin and Vincristine Dose Reductions in Patients With Advanced Hodgkin Lymphoma Treated With BEACOPP: An Analysis of the German Hodgkin Study Group HD12 and HD15 Trials
Authors: Heinz Haverkamp, Boris Böll, Dennis A. Eichenauer, Stephanie Sasse, Michael Fuchs, Peter Borchmann, Volker Diehl, Andreas Engert, Bastian von Tresckow
Journal: Journal of Clinical Oncology (2015)

The role of bleomycin and vincristine in the treatment of patients with advanced Hodgkin lymphoma (HL) is unclear, and the impact of dose reductions of these drugs on outcome and tolerability has not been systematically assessed. Because both drugs can cause significant toxicity and are frequently discontinued, we performed an analysis of patients with HL treated with BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) in the German Hodgkin Study Group HD12 and HD15 trials.Characteristics and outcome of patients were analyzed with respect to discontinuation of bleomycin and/or vincristine.With 3,309 patients with HL analyzed, bleomycin was discontinued in 17.6% and vincristine in 32.6%. A total of 157 patients (4.7%) received ≤ four cycles of bleomycin, and 218 (6.6%) received ≤ three cycles of vincristine; these were compared with patients receiving > four cycles of bleomycin or > three cycles of vincristine, respectively. After a median follow-up of 59 and 67 months for progression-free survival (PFS) and overall survival (OS), respectively, there was no significant difference in PFS or OS in patients receiving ≤ or > four cycles of bleomycin (5-year PFS difference, 1.7%; 95% CI, -4.2% to 7.6%; 5-year OS difference, 1.5%; 95% CI, -2.6% to 5.5%). Similarly, there was no significant difference in patients receiving ≤ or > three cycles of vincristine (5-year PFS difference, -1.3%; 95% CI, -5.6% to 3.1%; 5-year OS difference, -0.1%; 95% CI, -3.1% to 2.9%).Bleomycin and vincristine discontinuation because of drug-specific adverse effects does not affect the efficacy of treatment in this setting.
The exogenous surfactant Curosurf enhances phosphatidylcholine content in isolated type II cells
Authors: None Bourbon, B Chailley-Heu, B Gautier
Journal: European Respiratory Journal (1997)

The exogenous surfactant, Curosurf, contains proteins as well as phospholipids. We investigated the possibility that these might affect the reutilization of exogenous phospholipid by type II alveolar cells isolated from rat lung. The time course of incorporation into lamellar bodies of radioactivity from tritiated dipalmitoyl-phosphatidylcholine (DPPC) contained within liposomes was studied. Rates of uptake were compared between liposomes prepared from pure phospholipids and from Curosurf. The incorporation of labelled choline into newly synthesized phosphatidylcholine was also determined in the presence of both preparations. The rate of DPPC incorporation over the first 4 h was the same, but, after 6 and 8 h, the radioactivity associated with lamellar bodies was about 40% higher from Curosurf liposomes. By contrast, both Curosurf and the phospholipid mixture enhanced choline incorporation into phosphatidylcholine to the same extent. We conclude that Curosurf enhances the surfactant-related phosphatidylcholine content of type II cells by two mechanisms, one of which depends on the presence of proteins in exogenous surfactant. The difference in incorporation of radioactivity from liposome-associated labelled dipalmitoyl-phosphatidylcholine cannot be explained just by an increase in reutilization of choline from degraded dipalmitoyl-phosphatidylcholine.
Current Status of Oral Contraception
Authors: Edward T. Tyler
Journal: JAMA (1964)

Oral contraception, after eight years of use, is now recognized as the most effective method of voluntarily preventing pregnancy, probably because of a threefold action of the progesterone-estrogen combinations which inhibit ovulation, make cervical mucus impenetrable to sperm, and render the endometrium unsuitable for implantation. Several medical questions regarding safety are still unanswered, particularly those relating to thromboembolic complications; however, in this long-term study in which was used norethindronemestranol combinations, no serious complications were noted and laboratory studies have shown no statistically significant differences between users and nonusers of oral contraceptives. Minor side effects infrequently led to discontinuance of the method. Two dosage forms, one containing 10 mg of norethindrone and one containing 2 mg were equally effective.
Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist
Authors: W. Conrad Liles, Hal E. Broxmeyer, Elin Rodger, Brent Wood, Kai Hübel, Scott Cooper, Giao Hangoc, Gary J. Bridger, Geoffrey W. Henson, Gary Calandra, David C. Dale
Journal: Blood (2003)
Gonadotropin-Releasing Hormone (GnRH) Antagonists Promote Proapoptotic Signaling in Peripheral Reproductive Tumor Cells by Activating a Gαi-Coupling State of the Type I GnRH Receptor
Authors: Stuart Maudsley, Lindsay Davidson, Adam J. Pawson, Raymond Chan, Rakel López de Maturana, Robert P. Millar
Journal: Cancer Research (2004)

Gonadotropin-releasing hormone (GnRH) receptor agonists are extensively used in the treatment of sex hormone-dependent cancers via the desensitization of pituitary gonadotropes and consequent decrease in steroid sex hormone secretion. However, evidence now points to a direct inhibitory effect of GnRH analogs on cancer cells. These effects appear to be mediated via the Galpha(i)-type G protein, in contrast to the predominant Galpha(q) coupling in gonadotropes. Unlike Galpha(q) coupling, Galpha(i) coupling of the GnRH receptor can be activated by both agonists and antagonists. This unusual pharmacology suggested that the receptor involved in the cancer cells may not be the classical gonadotrope type I GnRH receptor. However, we have previously shown that a functional type II GnRH receptor is not present in man. In the present study, we show that GnRH agonists and selective GnRH antagonists exert potent antiproliferative effects on JEG-3 choriocarcinoma, benign prostate hyperplasia (BPH-1), and HEK293 cells stably expressing the type I GnRH receptor. This antiproliferative action occurs through a Galpha(i)-mediated activation of stress-activated protein kinase pathways, resulting in caspase activation and transmembrane transfer of phosphatidlyserine to the outer membrane envelope. Structurally related antagonistic GnRH analogs displayed divergent antiproliferative efficacies but demonstrated equal efficacies in inhibiting GnRH-induced Galpha(q)-based signaling. Therefore the ability of GnRH receptor antagonists to exert an antiproliferative effect on reproductive tumors may be dependent on ligand-selective activation of the Galpha(i)-coupled form of the type I GnRH receptor.
Overexpression of Apolipoprotein A-I Promotes Reverse Transport of Cholesterol From Macrophages to Feces In Vivo
Authors: YuZhen Zhang, Ilaria Zanotti, Muredach P. Reilly, Jane M. Glick, George H. Rothblat, Daniel J. Rader
Journal: Circulation (2003)

Background— Abundant data indicate that overexpression of apolipoprotein A-I (apoA-I) in mice inhibits atherosclerosis. One mechanism is believed to be promotion of reverse cholesterol transport, but no direct proof of this concept exists. We developed a novel approach to trace reverse transport of labeled cholesterol specifically from macrophages to the liver and feces in vivo and have applied this approach to investigate the ability of apoA-I overexpression to promote macrophage-specific reverse cholesterol transport. Method and Results— J774 macrophages were loaded with cholesterol by incubation with acetylated LDL, labeled with 3 H-cholesterol, and then injected intraperitoneally into mice. Plasma and feces were collected at 24 hours and 48 hours, when mice were exsanguinated, tissues were harvested, and all were analyzed for tracer counts. 3 H-cholesterol was found in the plasma, liver, and feces. For apoA-I overexpression, mice were injected intravenously with apoA-I adenovirus (10 11 particles per animal) 3 days before labeled macrophages were injected. ApoA-I overexpression led to significantly higher 3 H-cholesterol in plasma, liver, and feces. The amount of 3 H-tracer in the liver was 35% higher ( P &lt;0.05) and the 3 H-tracer excreted into feces over 48 hours was 63% higher ( P &lt;0.05) in apoA-I–expressing mice than in control mice. Conclusion— Injection of 3 H-cholesterol–labeled macrophage foam cells is a method of measuring reverse cholesterol transport specifically from macrophages to feces in vivo, and apoA-I overexpression promotes macrophage-specific reverse cholesterol transport.
Podoendin. A new cell surface protein of the podocyte and endothelium.
Authors: T W Huang, J C Langlois
Journal: The Journal of Experimental Medicine (1985)

A new cell surface protein, podoendin, has been identified in Sprague-Dawley rats, and isolated using monoclonal antibody (mAb) G4. The distribution of podoendin is restricted to the surface of glomerular podocytes, urinary surface of the parietal epithelium of Bowman's capsule, and the luminal surface of endothelial cells. The antibody does not crossreact with podocytes or endothelia of human or mice. In newborn rats, the appearance of podoendin on glomerular epithelium is attendant on podocyte differentiation during glomerulogenesis of metanephrogenic vesicles. It disappears when podocytes retract and efface foot processes in tissue culture. Thus, podoendin appears to be a cell differentiation-dependent surface protein of podocytes. Podoendin is a protein of 62 kD mobility on 5% polyacrylamide gel electrophoresis. It stains intensely with Coomassie blue, but gives negative reactions to carbohydrate (periodic acid/Schiff reaction) and polyanions (alcian blue, colloidal iron, and carbocyanine). It is distinct from the major sialoglycoprotein of podocyte fuzzy coat, podocalyxin (11). Podoendin isolated and purified from endothelium of lungs appears to be identical with that from podocytes and endothelium of kidneys. Injection of mAb G4 into left ventricle of rats resulted in intense decoration of the endothelium and podocyte surface within 30 min. The decoration persisted throughout the 3-d period of observation. This was not accompanied by complement (C3) fixation. Preliminary results showed that the rats developed moderate proteinuria (100 mg/ml protein in urine), which was associated with the presence of hyaline droplets in renal tubules, on the third day. The proteinuria was not accompanied by effacement of podocyte pedicels. There were no morphologic alterations indicating glomerular or vascular injury in the kidneys.
A Comparative Study of the Protein C Pathway in Septic and Nonseptic Patients with Organ Failure
Authors: Delphine Borgel, Caroline Bornstain, Pieter H. Reitsma, Nicolas Lerolle, Sophie Gandrille, Fouad Dali-Ali, Charles T. Esmon, Jean-Yves Fagon, Martine Aiach, Jean-Luc Diehl
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Severe sepsis is associated with an exacerbated procoagulant state with protein C (PC) system impairment. In contrast, the inflammatory and coagulation status of nonseptic patients with organ failure (OF) is less documented.Objectives: To compare coagulation activation, focusing on the PC system, and inflammatory status in septic and nonseptic patients with OF.Methods: Thirty patients with severe sepsis and 30 nonseptic patients were recruited at the onset of OF and compared with 30 matched healthy subjects. We performed an extensive analysis of the PC pathway, including plasma protein measurements and quantification of leukocyte expression of PC system receptors. In addition, we analyzed the inflammatory status, based on inflammation-related gene leukocyte expression.Measurements and Main Results: We observed coagulation activation, reflected by a similar increase in tissue factor mRNA expression, in the two patient groups when compared with the healthy subjects. Soluble thrombomodulin levels were higher in septic patients than in healthy control subjects, whereas PC, protein S, and soluble endothelial cell PC receptor levels were lower. Similar results were obtained in nonseptic patients with OF. Monocyte thrombomodulin overexpression, together with increased circulating levels of activated PC, suggests that the capacity for PC activation is at least partly preserved in both settings. No difference in the inflammatory profile was found between septic and nonseptic patients.Conclusions: The pathogenesis of OF in critical care patients is characterized by an overwhelming systemic inflammatory response and by exacerbated coagulation activation, independently of whether or not infection is the triggering event.Clinical trial registered with www.clinicaltrials.gov (NCT 00361725).
Familial Predisposition and Cosegregation Analysis of Adult Obstructive Sleep Apnea and the Sudden Infant Death Syndrome
Authors: Thorarinn Gislason, Johann Heidar Johannsson, Asgeir Haraldsson, Berglind Ran Olafsdottir, Helga Jonsdottir, Augustine Kong, Michael L. Frigge, Guðrun M. Jonsdottir, Hakon Hakonarson, Jeffrey Gulcher, Kari Stefansson
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Previous studies suggest a familial link between adult obstructive sleep apnea syndrome (OSAS) and sudden infant death syndrome (SIDS). However, most of these studies were hampered by the availability of too few cases of SIDS to draw conclusions. To examine the familial nature of this association in Iceland, hospital-based lists of all patients who were diagnosed with OSAS (n = 2,350) and SIDS (n = 58) from 1979 to 1998 were used to separately determine the familial occurrence of OSAS and SIDS and to search for evidence of cosegregation of these conditions in Icelandic families, using a nationwide genealogy database. The risk ratio for a first-degree relative of a patient with OSAS was 2.0 (1.7–2.8, 95% confidence interval). The risk ratio of the more severely affected patients with OSAS was slightly higher (2.3). Likewise, the kinship coefficient (KC) for the OSAS patient group, which determines the relatedness of the patients, was significantly larger than the mean KC of 1,000 matched control groups. Estimation of the KC for the SIDS group showed a trend toward significance when compared with control groups, but after excluding one of the half-siblings in the SIDS group from the analysis, the difference did not show any trend toward significance. Although the results of the analysis of the relatedness between all patients with OSAS and infants who died of SIDS were not significant, a trend toward significance was evident when the data were separately analyzed for the more severely affected patients with OSAS. Collectively, these results demonstrate a strong familial component in OSAS and suggest that infants who died of SIDS may have shared some of the same susceptibility factors with OSAS.
Anatomical and Functional Aspects of Testicular Descent and Cryptorchidism*
Authors: John M. Hutson, Suzanne Hasthorpe, Chris F. Heyns
Journal: Endocrine Reviews (1997)

I. Normal Development A. Anatomical aspects 1. Sexual development 2. The gubernaculum 3. Cranial suspensory ligament 4. Abdominal pressure B. Hormonal control and functional aspects of testicular descent 1. Mullerian inhibiting substance 2. Androgen 3. The genitofemoral nerve (GFN) 4. Calcitonin gene-related peptide (CGRP) II. Cryptorchidism A. Etiology B. Frequency C. Are some UDT acquired? D. Risks of infertility/malignancy E. Role of hormone therapy F. Timing of surgery
Bile acid studies in patients with Crohn's colitis.
Authors: P Rutgeerts, Y Ghoos, G Vantrappen
Journal: Gut (1979)

Bile acid studies were performed in patients with Crohn9s disease, radiologically confined to the colon. The bile acid pool size of 10 patients with isolated Crohn9s colitis was significantly lower than that of 10 normal control subjects (P less than 0.001) and of 10 ulcerative colitis patients (P less than 0.005). Measurements of 14C-excretion in breath and in 24 hours stool collections after the administration of 5 muCi 14C-glycocholate showed a normal 14C-excretion in breath and usually a markedly increased loss of 14C in the stool (greater than 7% of the dose). The simultaneous administration of 5 muCi 3H-polyethylene glycol MW 4000 (3H-PEG) as a marker indicated that the 14C/3H ratio in the patients with Crohn9s colitis was significantly greater than in a control series of patients with diarrhoea not due to bile acid malabsorption. Studies on the composition of duodenal bile showed a significantly decreased concentration of deoxycholic acid in duodenal bile. These observations suggest bile acid malabsorption in patients with Crohn9s disease apparently confined to the colon.
Peripheral Total and Differential Leukocyte Count in Diabetic Nephropathy
Authors: Fu-Mei Chung, Jack C.-R. Tsai, Dao-Ming Chang, Shyi-Jang Shin, Yau-Jiunn Lee
Journal: Diabetes Care (2005)

OBJECTIVE—Because of increasing evidence that white blood cells (WBCs) play a role in the development and progression of diabetes complications, this study aimed to investigate the relation of circulating total and differential leukocyte counts to nephropathy in patients with type 2 diabetes. Plasma leptin levels were also measured to investigate their role in peripheral leukocytosis. RESEARCH DESIGN AND METHODS—For this study, 1,480 subjects with type 2 diabetes who were enrolled in a disease management program were stratified according to urinary microalbumin and serum creatinine measurements. The total and differential leukocyte profiles of peripheral blood were measured and plasma leptin was examined by enzyme-linked immunosorbent assay. Demographic and potential metabolic confounding factors were analyzed with linear and logistic regression to calculate the effects of leukocyte count on diabetic nephropathy. RESULTS—The peripheral total WBC, monocyte, and neutrophil counts increased in parallel with the advancement of diabetic nephropathy. In contrast, the lymphocyte count decreased. When WBC counts were analyzed per quartile and as continuous variables after adjusting for age, sex, and other known risk factors with multiple regression analysis, peripheral total WBC, monocyte, neutrophil, and lymphocyte counts were independently and significantly associated with diabetic nephropathy. Plasma leptin levels increased in patients with nephropathy and correlated significantly with total WBC count (r = 0.194, P = 0.014). CONCLUSIONS—Because leukocytes are activated and secrete cytokines in the diabetic state and leptin stimulates leukocyte proliferation and differentiation, our results suggest that circulating leukocytes contribute to the development and progression of nephropathy, partially through the effects of leptin, in patients with type 2 diabetes.
Making sense in a nonsense reading frame: suppression of cardiac sodium channel dysfunction
Authors: E. Schulze-Bahr
Journal: Cardiovascular Research (2009)

In the past few years, cardiologists, geneticists, physicians, and also patients have begun to realize the unexpected complexity underlying inherited forms of arrhythmias or cardiomyopathies. The number of disease-causing genes for congenital long-QT syndrome, hypertrophic cardiomyopathy, and other conditions has now reached the double-digit range (locus heterogeneity). As a rule of the thumb, most mutations are family-specific (‘private’) events and localize without any preference within the main regions of a gene (allelic heterogeneity).1 The identification of inherited cardiac ion channel dysfunction as the cause of familial arrhythmias stimulated many research teams all over the world to specifically target and modulate ion channels in order to restore function and reduce arrhythmogenesis.2–5 For ion channel gene alterations that are not associated with a gain-of-function (where channel function can be reduced by drug-directed inhibition) but a loss-of-function, such a targeted approach is rather more complex and logically would encompass increasing expression of the wild-type gene or restoring intracellular trafficking deficiency of mutant ion channel proteins, e.g. by the use of chaperones.6–8 Indeed, loss-of-function mutations are the predominant features for … 

*Corresponding author. Institut fur Genetik von Herzerkrankungen (IfGH), Universitatsklinikum Munster (UKM), Domagkstr. 3, D-48149 Munster, Germany. Tel. +49 251 83 52982; fax: +49 251 83 52980. E-mail address : heart{at}uni-muenster.de
Pharmacological Treatment of the Overweight Patient
Authors: George A. Bray, Frank L. Greenway
Journal: Pharmacological Reviews (2007)

To use medications properly for treatment of the overweight patient, it is important to start with a framework based on the realities associated with this treatment. These are briefly summarized below: 1. Overweight is due to an imbalance between energy intake and energy expenditure. 2. Drugs
Personalised medicine in exacerbations of COPD: the beginnings
Authors: Sanjay Sethi
Journal: European Respiratory Journal (2012)

Exacerbations of chronic obstructive pulmonary disease (COPD) are inflammatory events induced by infection [1]. Therefore, the use of antimicrobial and anti-inflammatory medications in exacerbations appears logical. However, the evidence that antibiotics and corticosteroids are beneficial in the treatment of exacerbations is relatively sparse, and only a meta-analytic approach has given us sufficient confidence in the use of these treatments [2, 3]. Placebo-controlled and observational studies in hospitalised patients with COPD exacerbations have shown the benefit of antibiotics and steroids [4–6]. This has led to current recommendations for treating all hospitalised exacerbations with both antibiotics and steroids. However, as we appreciate the heterogeneity of infection and inflammation in exacerbations, using the same treatment in all exacerbations does not appear appropriate. Bacterial infection causes approximately 50% of exacerbations; therefore, antibiotic use is probably unnecessary in the other 50% [1]. Eosinophilic inflammation is seen in a third of exacerbations, so corticosteroids may be of limited benefit in a substantial proportion of exacerbations [7].

In a hospitalised patient with a COPD exacerbation, the cost of antibiotics accounts for a small fraction of the total cost of care. However, everyone is well aware of the dangers of inappropriate and excessive antibiotic use with regards to selection of antibiotic resistant pathogens and adverse effects. Therefore, discriminating exacerbations that are bacterial in origin from those that are not would help us target antibiotic therapy. Sputum cultures lack the sensitivity, specificity and speed to be such a discriminatory tool. Biomarkers such as …
Endoscopic examination of the duodenal bulb: clinical evaluation of forward- and side-viewing fibreoptic systems in 200 cases
Authors: P. R. Salmon, P. Brown, T. Htut, A. E. Read
Journal: Gut (1972)

Two-hundred fibreoptic examinations of the duodenal bulb were carried out on 149 patients. The importance of combining the initial examination with a general endoscopic survey of the oesophagus and stomach is stressed. At the present time full examination of the duodenal bulb requires the use of both a side-viewing and forward-viewing endoscope in more than a quarter of cases. The safety and acceptability to the patient of multiple endoscopic examinations carried out as an outpatient procedure has been demonstrated, and the value of the procedure in <i>x</i>-ray negative dyspepsia, in the follow up of ulcer therapy, and in acute upper gastrointestinal haemorrhage has been shown.