tbuckley/cabot-search huggingface dataset:
Steroids in Adult Men With Type 1 Diabetes
Authors: Eveline W.C.M. van Dam, Jacqueline M. Dekker, Eef G.W.M. Lentjes, Fred P.T.H.M. Romijn, Yvo M. Smulders, Wendy J. Post, Johannes A. Romijn, H. Michiel J. Krans
Journal: Diabetes Care (2003)

OBJECTIVE—To compare steroids and their associations in men with type 1 diabetes and healthy control subjects. RESEARCH DESIGN AND METHODS—We studied 52 adult men with type 1 diabetes without microvascular complications, compared with 53 control subjects matched for age and BMI. Steroids and their binding globulins were assessed in a single venous blood sample and a 24-h urine sample. RESULTS—In adult men with type 1 diabetes, total testosterone did not differ from healthy control subjects, but sex hormone–binding globulin (SHBG) (42 [14–83] vs. 26 [9–117] nmol/l, P &amp;lt; 0.001), cortisol-binding globulin (CBG; 0.87 ± 0.17 vs. 0.73 ± 0.10 nmol/l, P &amp;lt; 0.001), and cortisol levels (0.46 ± 0.16 vs. 0.39 ± 0.14 nmol/l, P &amp;lt; 0.01) were higher. The free testosterone index was lower (60 [17–139] vs. 82 [24–200], P &amp;lt; 0.001), and the calculated free testosterone was slightly lower (497 [115] vs. 542 [130], P &amp;lt; 0.064), but the pituitary-gonadal axis was not obviously affected in type 1 diabetes. The calculated free serum cortisol was not different, and 24-h urinary free cortisol excretion was lower in type 1 diabetes (121 [42–365] vs. 161 [55–284] nmol/24 h, P &amp;lt; 0.009). Testosterone was mainly associated with SHBG. Estimated portal insulin was a contributer to SHBG in control subjects but not in type 1 diabetes. Cortisol was associated with CBG. HbA1c contributed to CBG in men with diabetes but not in control subjects, whereas estimated portal insulin did not contribute. CONCLUSIONS—Adult men with fairly controlled type 1 diabetes without complications who are treated with subcutaneous insulin have a tendency to hypogonadism, as reflected by lower free testosterone levels in the presence of similar total testosterone levels and higher SHBG levels.
Flow cytometric analysis of the effect of dithiothreitol on leukocyte surface markers
Authors: D. Loppow, M. Böttcher, G. Gercken, H. Magnussen, R.A. Jörres
Journal: European Respiratory Journal (2000)

Pretreatment with dithiothreitol (DTT) is necessary to dissolve mucus in samples of induced sputum prior to analysis. However, DTT may affect cell surface markers which are essential for lymphocyte subtyping. Therefore, the aim of this study was to evaluate the effect of DTT on an appropriate panel of surface markers. Peripheral blood leukocytes were used because these cells, in contrast to sputum cells, could be obtained without DTT treatment. Peripheral blood from healthy donors was incubated with either DTT according to standard sputum procedures or phosphate-buffered saline (PBS), washed and incubated with fluorochrome-labelled antibodies. After lysis of erythrocytes, analysis was performed using a calibrated flow cytometer. Leukocyte populations were identified by their light scattering properties. For analysis, fluorescence intensity was compared between DTT- and PBS-treated samples. After treatment with DTT, fluorescence intensity was significantly increased in CD16-positive granulocytes; it was reduced in CD2-positive lymphocytes, CD45-positive lymphocytes and CD14-positive monocytes (p &lt; or = 0.001). These changes occurred in all samples. The fluorescence intensity of CD3-, CD4-, CD8-, CD19-, CD56- and histocompatibility leukocyte antigen DR-positive lymphocytes was not altered by DTT. However, there were statistically significant (p&lt;0.001), although small, changes in the percentages of leukocytes. The present data demonstrate that, although dithiothreitol as used in sputum analysis affects some surface markers of peripheral blood leukocytes, comparability between samples concerning lymphocyte surface markers is preserved. Therefore, it is suggested that treatment of sputum samples with dithiothreitol does not invalidate the immunocytochemical analysis of lymphocytes.
National Practice Patterns and Time Trends in Androgen Ablation for Localized Prostate Cancer
Authors: M. R. Cooperberg, G. D. Grossfeld, D. P. Lubeck, P. R. Carroll
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Recent reports have suggested that growing numbers of patients with localized prostate cancer are receiving androgen deprivation therapy as primary or neoadjuvant treatment, yet sparse clinical evidence supports the use of such treatment except among patients with high-risk or locally advanced disease receiving external beam radiotherapy. We describe national trends in the use of androgen deprivation therapy for localized disease. Methods: CaPSURE is an observational database of 7195 patients with prostate cancer. This study included 3439 of these patients who were diagnosed since 1989, had clinical staging information available, and were treated with radical prostatectomy, radiation therapy, or primary androgen deprivation therapy (PADT). High-, intermediate-, and low-risk groups were defined by serum prostate-specific antigen level, Gleason score, and clinical tumor stage. Time trends in the use of PADT and neoadjuvant androgen deprivation therapy (NADT) were analyzed. All statistical tests were two-sided. Results: Rates of PADT use rose sharply between 1989 and 2001, from 4.6% (95% confidence interval [CI] = 3.4% to 5.8%) to 14.2% (95% CI = 12.2% to 16.2%), from 8.9% (95% CI = 7.3% to 10.5%) to 19.7% (95% CI = 17.5% to 21.9%), and from 32.8% (95% CI = 29.9% to 35.7%) to 48.2% (95% CI = 45.1% to 51.3%) (all P<.001) in low-, intermediate-, and high-risk groups, respectively. NADT use also increased in association with radical prostatectomy (2.9% [95% CI = 2.1% to 3.7%] to 7.8% [95% CI = 6.5% to 9.1%] of patients, P = .003) and external beam radiotherapy (9.8% [95% CI = 7.5% to 12.1%] to 74.6% [95% CI = 70.8% to 78.4%], P<.001) across all risk levels combined. Rates of NADT use among patients treated with brachytherapy also increased but not statistically significantly (7.4% [95% CI = 3.5% to 11.3%] to 24.6% [95% CI = 18.2% to 31.0%], P = .100). Conclusions: Rates of both PADT and NADT are increasing across risk groups and treatment types. Future clinical trials must define more clearly the appropriate role of hormonal therapy in localized prostate cancer, and their results should shape updated practice guidelines.
Predictive value of response to treatment of T-lymphocyte subpopulations in idiopathic pulmonary fibrosis
Authors: E Fireman, N Vardinon, M Burke, S Spizer, S Levin, A Endler, D Stav, M Topilsky, A Mann, Y Schwarz, S Kivity, J Greif
Journal: European Respiratory Journal (1998)

T-cell types are important in maintaining immune homeostasis in the lung and their imbalance may be associated with several diseases. We examined the relationship between bronchoalveolar lavage (BAL) T-cell subset profiles and the clinical course of 46 patients with idiopathic pulmonary fibrosis (IPF). A flow cytometry cell sorter (FACS) was used to analyse the T-cell subsets. Pulmonary function tests (PFT) were performed at baseline and 6-12 months later. Patients were divided into two groups according to their CD4/CD8 ratio: CD4/CD8 >1 (group 1, n=21); and CD4/CD8 <1 (group 2, n=25). A lower percentage of lymphocytes, a higher percentage of CD8/S6F1 cells (cytotoxic T-lymphocytes) and a higher percentage of neutrophils were found in the BAL in group 2 compared to group 1 (11+/-7.5% versus 19+/-13.2%; p=0.024 and 29.8+/-17.6% versus 13.3+/-6.9%; p=0.068, respectively for lymphocytes and cytotoxic T-lymphocytes; and 8+/-11% versus 29+/-27%; p=0.003 for neutrophils). Inversely, in the peripheral blood, the distribution of CD8/S6F1 cells was lower in group 1 than in group 2 (8.3+/-6.9% versus 33.4+/-16.5%; p=0.0048). The patients were followed over a period of 1 yr in order to test whether those findings could determine efficacy of therapy. The baseline transfer factor of the lung for carbon monoxide (TL,CO) capacity in group 1 and group 2 was 59+/-22% and 51+/-21%, respectively (p=0.29), but only in group 1 was the TL,CO capacity improved significantly in response to steroids treatment after 6-12 months. IPF patients with a higher percentage of lymphocytes, a lower percentage of neutrophils, CD4/CD8 >1 and a low percentage of CD8/S6F1 may have a more benign course of disease. These parameters may identify an early stage of reversible disease responsive to therapy. We conclude that these measurements may be a useful tool in monitoring response to treatment in patients with idiopathic pulmonary fibrosis.
Dapsone as first line therapy for bullous pemphigoid
Authors: V.A. VENNING, P.R. MILLARD, F. WOJNAROWSKA
Journal: British Journal of Dermatology (1989)

In an open study, a total of 18 patients with proven bullous pemphigoid (16 new patients and two in relapse) were treated with a trial of dapsone (17 patients) or sulphonimide (one patient). Overall, eight patients were controlled on one of these agents as the sole treatment (44%). Six patients had a partial, but inadequate response, while four did not respond. The responses to the sulpha drugs were generally rapid, i.e. within 2 weeks, and the maximum doses used in any patient were 100 mg/day dapsone and 1.5 g/day of sulphapyridine or sulphamethoxypyridazine. Significant side-effects to dapsone occurred in six of the 17 patients. A trial of a sulphone or sulphonamide drug is warranted in bullous pemphigoid both as an initial treatment or in the treatment of relapse, particularly when there is a contraindication to the use of corticosteroids. Side-effects are common and therapy needs to be closely monitored.
INACTIVATION OF ENDOTOXIN BY A HUMORAL COMPONENT
Authors: Robert C. Skarnes, Fred S. Rosen, Murray J. Shear, Maurice Landy
Journal: The Journal of Experimental Medicine (1958)

A humoral substance which inactivates endotoxin in vitro has been shown to be clearly distinguishable from complement, properdin, and specific antibody. For the present, it is designated "endotoxin-detoxifying component" or EDC. Animal species could be grouped in three categories with regard to the EDC activity of their sera; rat serum was highly potent; chimpanzee, dog, horse, and guinea pig sera were much less active; mouse, rabbit, and sheep sera exhibited no activity. The EDC potency of human sera varied widely, ranging from high to barely discernible activity. In contrast to the variations of EDC potency in serum, citrated plasma from all species manifested high potency of about the same magnitude. The influence of time, temperature, pH, and concentration of reactants on the inactivation of endotoxin by EDC was examined. EDC activity in plasma and serum was found to be labile to beating at 56 degrees C. for 1 hour. Bacterial endotoxins, derived by different isolation procedures from smooth and rough Gram-negative species, varied considerably in susceptibility to EDC action.
Role of AIF in cardiac apoptosis in hypertrophic cardiomyocytes from Dahl salt-sensitive rats
Authors: Sangita Choudhury, Soochan Bae, Sheetal R. Kumar, Qingen Ke, Bhargavi Yalamarti, Jun H. Choi, Lorrie A. Kirshenbaum, Peter M. Kang
Journal: Cardiovascular Research (2009)

The caspases are thought to be central mediators of the apoptotic program, but recent data indicate that apoptosis may also be mediated by caspase-independent mechanisms such as apoptosis-inducing factor (AIF).The role of AIFinduced apoptosis in heart, however, is currently not well understood.The aim of this study was to investigate the presence of and conditions for AIF-induced cardiac apoptosis in vitro. Methods and resultsHypertrophic cardiomyocyte (H-CM) cultures were prepared from the hearts of Dahl salt-sensitive rats fed a high salt diet.Apoptotic stimulation induced by hypoxia/reoxygenation or staurosporine (1 mM) enhanced AIF release in H-CMs compared with non-hypertrophic cardiomyocytes (N-CMs).Caspase inhibition using zVAD.fmk(25 mM) or overexpression of CrmA using recombinant adenovirus only partially protected N-CMs from apoptosis (63 + 0.93%) and provided no significant protection against apoptosis in hypertrophic cells (23 + 1.03%).On the other hand, poly-ADP-ribose polymerase inhibition using 4-AN (20 mM) during apoptotic stimulation blocked the release of AIF from mitochondria and significantly improved cell viability in hypertrophied cardiomyocytes (74 + 1.18%). ConclusionA caspase-dependent, apoptotic pathway is important for N-CM death, whereas a caspase-independent, AIF-mediated pathway plays a critical role in H-CMs.
Treatment of severe systemic inflammatory response syndrome and sepsis with a novel bradykinin antagonist, deltibant (CP-0127). Results of a randomized, double-blind, placebo-controlled trial. CP-0127 SIRS and Sepsis Study Group
Authors: A. M. Fein
Journal: JAMA (1997)

To test the effect of a novel bradykinin antagonist, deltibant (CP-0127), on survival, organ dysfunction, and other outcomes in patients with the systemic inflammatory response syndrome (SIRS) and presumed sepsis.Multicenter, randomized, placebo-controlled, double-blind, parallel, dose-ranging trial. Follow-up for 28 days or until death.A total of 47 US referral hospitals.A total of 504 patients with SIRS and documented evidence of infection plus either hypotension or dysfunction of 2 organ systems.Three-day continuous intravenous infusion of either placebo or 1 of 3 doses (0.3, 1.0, or 3.0 microg x kg(-1) x min(-1)) of deltibant. Concurrent therapy at the discretion of the treating physician.Risk-adjusted, 28-day, log-normal intent-to-treat survival analysis. Risk adjustment was performed using a study-specific risk model derived from the APACHE III database.Deltibant had no significant effect on risk-adjusted 28-day survival. In a posthoc analysis, risk-adjusted 7-day survival showed a nonsignificant trend toward improvement (P=.09). The 28-day risk-adjusted survival in the prospectively defined subset of patients with gram-negative infections showed a statistically significant improvement (P=.005).Deltibant may have some effect on survival in patients with SIRS and gram-negative sepsis; however, additional studies would be required to prove this.
Development of the human dispermic embryo
Authors: A H Sathananthan, J J Tarin, L Gianaroli, S C Ng, V Dharmawardena, M C Magli, R Fernando, A O Trounson
Journal: Human Reproduction Update (1999)

In a recent CD-ROM, we portrayed the microstructure of the pre-implantation human embryo (Sathananthan et al., 1999), which was a multimedia production with computer colour-enhanced electron micrographs of mainly monospermic embryos. This disk portrays light and electron micrographs of over 250 tripronuclear (3PN), dispermic, human embryos during pre-implantation development, viewed in thick and thin Araldite sections, as well as appearances of whole embryos flat embedded in Araldite blocks visualized with the light microscope. The 100 figures were computerized (IBM TIFF format), edited and labelled using Adobe Photoshop 5. Some of the figures were coloured on computer. The early development of 3PN embryos overtly resembles that of normal embryos but there are important differences in their microstructure which are portrayed in this presentation. This is a multicentric study involving researchers from four IVF centres.
Prevention and Treatment of Cytomegalovirus Infection
Authors: J D Meyers
Journal: Annual Review of Medicine (1991)

Although a rare cause of symptomatic infection in normal persons, cytomegalovirus (CMV) is of increasing importance in the immunocompromised host. Effective treatment is now available with ganciclovir; foscarnet offers a possible alternative, especially for patients infected with ganciclovir-resistant CMV strains. Primary CMV infection can be prevented by serologic screening of blood (and organ) donors. An alternative approach for prevention of transfusion-associated CMV infection is leukocyte depletion by filtration. Immunoglobulin immunoprophylaxis remains controversial but may be effective in ameliorating disease in renal allograft patients. Acyclovir is partially effective in suppressing infection in already seropositive patients, but ganciclovir and foscarnet offer more promise for this purpose.
Left Ventricular Volume Measurements in Man by Thermodilution*
Authors: J. David Bristow, Rodney L. Crislip, Cyrus Farrehi, Waldo E. Harris, Richard P. Lewis, Donald W. Sutherland, Herbert E. Griswold
Journal: Journal of Clinical Investigation (1964)

A safe, rapid method for estimating left ventricular volume in man during the course of hemodynamic studies should prove helpful in the assessment of cardiac disease and useful in physiological research. It is the purpose of this report to present left ventricular volume measurements in man that were obtained by an indicator dilution method which employs cold as the indicator. This circulatory indicator has been studied by several workers (1-4) and has been used for left ventricular volume determinations in animals previously (5-10). The method employed was adapted from those used by Rapaport and his co-workers for left ventricular volume measurements in the dog (7) and right ventricular studies in man (11).
Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre
Authors: A Grieco
Journal: Gut (2005)

<b>Background:</b> Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups <b>Methods:</b> We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. <b>Results:</b> Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, α fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p&lt;0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. <b>Conclusions:</b> Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.
Response to Letter Regarding Article, “Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Plaque Characteristics: The PREDICTION Study”
Authors: Peter H. Stone, Shigeru Saito, Saeko Takahashi, Yasuhiro Makita, Shigeru Nakamura, Tomohiro Kawasaki, Akihiko Takahashi, Takaaki Katsuki, Sunao Nakamura, Atsuo Namiki, Atsushi Hirohata, Toshiyuki Matsumura, Seiji Yamazaki, Hiroyoshi Yokoi, Shinji Tanaka, Satoru Otsuji, Fuminobu Yoshimachi, Junko Honye, Dawn Harwood, Martha Reitman, Ahmet U. Coskun, Michail I. Papafaklis, Charles L. Feldman
Journal: Circulation (2013)
Regulation of hypertrophy and atrophy in cultured adult heart cells.
Authors: W A Clark, S J Rudnick, J J LaPres, L C Andersen, M C LaPointe
Journal: Circulation Research (1993)

Mechanical loading and alpha-adrenergic receptor stimulation have both been shown to induce hypertrophy in isolated neonatal heart cells. The present study examined the effects of adrenergic hormones and contractile activity on the hypertrophic response in isolated adult feline cardiomyocytes maintained for more than 14 days in insulin- and serum-supplemented medium. Measurements of the hypertrophic response included cell size, total protein content, myosin heavy chain content, and the time course of activation of increased protein synthesis. Reactivation of the "fetal" gene program was evaluated by secretion of atrial natriuretic factor (ANF) into the medium. Significant myocyte hypertrophy was induced in both quiescent myocytes treated with alpha 1-adrenergic agonists and in beating myocytes treated with beta-adrenergic agonists. However, there were both quantitative and qualitative differences in the response to each type of stimulation. alpha-Adrenergic agonists promoted an increase in cell size, protein content, and ANF secretion but not myofibrillar reorganization, which was observed only in beating myocytes. In contrast to results reported for neonatal heart cells, determinants of hypertrophy in beating myocytes exceeded those in nonbeating alpha 1-adrenergic agonist-treated heart cells in every parameter examined. In addition, in the case of both beating and alpha-adrenergic stimulation, there were marked time-dependent variations in rates of protein synthesis over the interval of 4 hours to 7 days of treatment with each type of stimulus. Differences were also encountered in correlations between rates of protein synthesis and protein accumulation over this interval. The effect of beating was particularly important both to the reorganization of myofibrillar structure and the metabolism of myosin heavy chain. In cultures in which beating was inhibited with the calcium channel antagonist nifedipine, the loss of myosin heavy chain was significantly greater than that of total protein.
Role of Permanent Pacing to Prevent Atrial Fibrillation
Authors: Bradley P. Knight, Bernard J. Gersh, Mark D. Carlson, Paul A. Friedman, Robert L. McNamara, S. Adam Strickberger, Hung Fat Tse, Albert L. Waldo
Journal: Circulation (2005)

This advisory summarizes the current database on pacing modalities and algorithms used to prevent and terminate atrial fibrillation (AF). On the basis of the evidence indicating that ventricular pacing is associated with a higher incidence of AF in patients with sinus node dysfunction, a patient who has a history of AF and needs a pacemaker for bradycardia should receive a physiological pacemaker (dual chamber or atrial) rather than a single-chamber ventricular pacemaker. For patients who need a dual-chamber pacemaker, efforts should be made to program the device to minimize the amount of ventricular pacing when atrioventricular conduction is intact. Many pacemakers and implantable defibrillators have features designed to prevent AF and to terminate AF with rapid atrial pacing. The evidence to support their use is limited, although these algorithms appear to be safe and usually add little additional cost. For patients who have a bradycardia indication for pacing and also have AF, no consistent data from large randomized trials support the use of alternative single-site atrial pacing, multisite right atrial pacing, biatrial pacing, overdrive pacing, or antitachycardia atrial pacing. Even fewer data support the use of atrial pacing in the management of AF in patients without symptomatic bradycardia. At present, permanent pacing to prevent AF is not indicated; however, additional studies are ongoing, which will help to clarify the role of permanent pacing for AF.