tbuckley/cabot-search huggingface dataset:
Oral Sulodexide Reduces Albuminuria in Microalbuminuric and Macroalbuminuric Type 1 and Type 2 Diabetic Patients
Authors: Giovanni Gambaro, Ida Kinalska, Adrian Oksa, Peter Pont’uch, Miluse Hertlová, Jindrich Olsovsky, Jacek Manitius, Domenico Fedele, Stanislaw Czekalski, Jindriska Perusicová, Jan Skrha, Jan Taton, Wladyslaw Grzeszczak, Gaetano Crepaldi
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Diabetic nephropathy may be effectively prevented and treated by controlling glycemia and administering angiotensin-converting enzyme (ACE) inhibitors. However, strict metabolic control can be difficult, and ACE inhibitors may be poorly tolerated and only partially effective, particularly in diabetes mellitus type 2 (DM2), warranting the search for ancillary treatment. Sulodexide is a glycosaminoglycan, a new class of drug that has demonstrated nephroprotective activity in experimental investigations. The Di.N.A.S. study was a randomized, double-blind, placebo-controlled, multicenter, dose-range finding trial to evaluate the extent and duration of the hypoalbuminuric effect of oral sulodexide in diabetic patients. A total of 223 microalbuminuric and macroalbuminuric DM1 and DM2 patients with serum creatinine ≤150 μmol/L and stable BP and metabolic control were recruited. They were randomly allocated to one of four groups: 50 mg/d, 100 mg/d, or 200 mg/d sulodexide daily or placebo for 4 mo (T0 to T4), with 4 mo of follow-up after drug suspension (T4 to T8). Treatment with 200 mg/d sulodexide for 4 mo significantly reduced log albumin excretion rate (logAER) from 5.25 ± 0.18 at T0 to 3.98 ± 0.11 at T4 (<i>P</i> &lt; 0.05), which was maintained till T8 (4.11 ± 0.13; <i>P</i> &lt; 0.05 <i>versus</i> T0). Moreover, the sulodexide-induced percent reductions in AER at T4 were significantly different from the placebo value at T4 and approximately linear to dose increments (30% [confidence limits, 4 to 49%], <i>P</i> = 0.03; 49% [30 to 63%], <i>P</i> = 0.0001; and 74% [64 to 81%], <i>P</i> = 0.0001 in the sulodexide 50, 100, and 200 mg/d groups, respectively. At T8, the sulodexide 200 mg/d group maintained a 62% (45 to 73%) AER significant reduction <i>versus</i> placebo (<i>P</i> = 0.0001). Subanalysis by type of diabetes (DM1 <i>versus</i> DM2, microalbuminuric <i>versus</i> macroalbuminuric, or on concomitant ACE inhibitors <i>versus</i> not on ACE inhibitors) demonstrated similar findings. These effects were obtained without any significant variation in metabolic control and BP or serum creatinine. Very few adverse events were reported; none were serious. In conclusion, a 4-mo course of high doses of sulodexide significantly and dose-dependently improves albuminuria in DM1 and DM2 patients and micro- or macroalbuminuric patients with or without concomitant ACE inhibition. The effect on albuminuria is long-lasting and seemingly additive to the ACE inhibitory effect.
Phase III Study of Fluorouracil, Leucovorin, and Levamisole in High-Risk Stage II and III Colon Cancer: Final Report of Intergroup 0089
Authors: Daniel G. Haller, Paul J. Catalano, John S. Macdonald, Mark A. O'Rourke, Michael S. Frontiera, Don V. Jackson, Robert J. Mayer
Journal: Journal of Clinical Oncology (2005)

In 1990, fluorouracil (FU) plus levamisole for 1 year became standard adjuvant treatment for patients with high-risk stages II and III colon cancer. Intergroup (INT) 0089 assessed the relative contributions of leucovorin and levamisole in such patients.From 1988 to 1992, 3,794 patients were randomly assigned. Experimental treatment consisted of one of three chemotherapy regimens: the low-dose leucovorin plus FU (Mayo Clinic; LDLV) regimen, the high-dose leucovorin plus FU (Roswell Park; HDLV) regimen, and the low-dose leucovorin plus levamisole plus FU (LDLV plus LEV) regimen, each administered for 30 to 32 weeks. The control arm was levamisole plus FU (LEV) for 1 year.After a median follow-up of 10 years, of 3,561 eligible patients, 1,691 (47%) have died and 1,330 (37%) have experienced disease recurrence; 137 (10%) of those experiencing recurrence are still alive. A total of 481 patients (13%) died without evidence of recurrence, and 1,723 (48%) are alive and disease free. Although there were toxicity differences among the four arms, none was statistically superior in disease-free or overall survival.The 6- to 8-month regimens of LDLV and HDLV without levamisole used in this trial, rather than the previous standard regimen of 12 months of LEV, have become widely used. INT-0089 has long-term follow-up of the largest clinical trial of patients with high-risk colon cancer, documenting not only the durability of the treatment effects, but also the natural history of patients with high-risk colon cancer, and analyses of treatment based on age, race, and comorbid conditions such as obesity, diabetes, and second primary cancers.
Zinc-alpha2-glycoprotein Expression as a Predictor of Metastatic Prostate Cancer Following Radical Prostatectomy
Authors: Susan M. Henshall, Lisa G. Horvath, David I. Quinn, Sarah A. Eggleton, John J. Grygiel, Phillip D. Stricker, Andrew V. Biankin, James G. Kench, Robert L. Sutherland
Journal: JNCI Journal of the National Cancer Institute (2006)

The risk of metastatic progression for prostate cancer patients who undergo radical prostatectomy is best estimated presently based on prostate-specific antigen (PSA) doubling time (PSADT). However, additional markers of risk are needed to identify patients who may benefit from aggressive salvage treatment. A decrease in zinc-alpha2-glycoprotein (AZGP1) mRNA levels in malignant prostate epithelium was previously shown to predict biochemical recurrence, as defined by rising levels of serum PSA after radical prostatectomy. We assessed the reliability with which AZPG1 expression could predict clinical recurrence and metastatic progression. Using immunohistochemical methods, we analyzed AZPG1 expression in malignant prostate epithelium in prostatectomy specimens from 228 prostate cancer patients. Low (i.e., absent or weak) AZGP1 expression was associated with clinical recurrence (defined as confirmed localized recurrence, metastasis, or death from prostate cancer; hazard ratio [HR] = 4.8, 95% confidence interval [CI] = 2.2 to 10.7, P <.001) and with bony metastases or death from prostate cancer (HR = 8.0, 95% CI = 2.6 to 24.3, P <.001). Among the 17 patients in the cohort in whom clinical recurrence was associated with short PSADT, absent or weak AZGP1 expression was observed in 13 patients. If these preliminary findings are validated in independent cohorts, the measurement of AZGP1 levels in radical prostatectomy specimens may permit an accurate and timely assessment of risk of metastatic progression after radical prostatectomy.
On the Parallelism between the Three Thermic Mechanisms and Dr. Hughlings Jackson's Three Levels
Authors: W. H. White
Journal: BMJ (1890)

IN his Lumleian Lectures, which have recently appeared in the JOURNAL, Dr. Hughlings Jackson refers to his oft suggested hypothesis that there are three levels of the central nervous sys- tem.The lowest, or first level, consists of the cord, medulla, and pons; it is the first evolved, and represents the simplest move- ments of all parts of the body.The middle, or second level, is composed of the Rolandic motor area and the corpus striatum; it
New Prognostic Factors for Stage I Testicular Cancer: But Will They Make It to Broadway?
Authors: Derek Raghavan
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.07.967 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14559887 New Prognostic Factors for Stage I Testicular Cancer: But Will They Make It to Broadway? Derek RaghavanxDerek RaghavanSearch for articles by this author Show More Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA https://doi.org/10.1200/JCO.2003.07.967 Full Text PDF Figures and Tables "New Prognostic Factors for Stage I Testicular Cancer: But Will They Make It to Broadway?." Journal of Clinical Oncology, 21(22), pp. 4075–4076© 2003 by American Society of Clinical Oncology
Effectiveness and Cost Effectiveness of Expanding Harm Reduction and Antiretroviral Therapy in a Mixed HIV Epidemic: A Modeling Analysis for Ukraine
Authors: Sabina S. Alistar, Douglas K. Owens, Margaret L. Brandeau
Journal: PLoS Medicine (2011)

A cost-effectiveness study by Sabina Alistar and colleagues evaluates the effectiveness and cost effectiveness of different levels of investment in methadone, ART, or both, in the mixed HIV epidemic in Ukraine.
Correlation Between O<sup>6</sup>-Methylguanine-DNA Methyltransferase and Survival in Inoperable Newly Diagnosed Glioblastoma Patients Treated With Neoadjuvant Temozolomide
Authors: Olivier L. Chinot, Maryline Barrié, Stephane Fuentes, Nathalie Eudes, Sophie Lancelot, Philippe Metellus, Xavier Muracciole, Diane Braguer, L'Houcine Ouafik, Pierre-Marie Martin, Henry Dufour, Dominique Figarella-Branger
Journal: Journal of Clinical Oncology (2007)

This phase II study evaluated the efficacy and safety of a 7-day on/7-day off regimen of temozolomide before radiotherapy (RT) in patients with inoperable newly diagnosed glioblastoma.Patients received temozolomide (150 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days; 7 days on/7 days off) for up to four cycles before conventional RT (2-Gy fractions to a total of 60 Gy) and for four cycles thereafter or until disease progression. The primary end point was tumor response. Tumor tissue from 25 patients was analyzed for O6-methylguanine-DNA methyltransferase (MGMT) expression.Twenty-nine patients with a median age of 60 years were treated, and 28 were assessable for response. Seven (24%) of 29 patients had a partial response, nine patients (31%) had stable disease, and 12 patients (41%) had progressive disease. Median progression-free survival (PFS) time was 3.8 months, and median overall survival (OS) time was 6.1 months. Patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median, 5.5 v 1.9 months, respectively; P = .009) and OS (median, 16 v 5 months, respectively; P = .003). The most common grade 3 and 4 toxicities were thrombocytopenia (20%) and neutropenia (17%).This dose-dense temozolomide regimen resulted in modest antitumor activity with an acceptable safety profile in the neoadjuvant setting, and expression of MGMT correlated with response to temozolomide. However, this treatment approach seems to be inferior to standard concomitant RT plus temozolomide.
Comparisons between Novel Oral Anticoagulants and Vitamin K Antagonists in Patients with CKD
Authors: Ziv Harel, Michelle Sholzberg, Prakesh S. Shah, Katerina Pavenski, Shai Harel, Ron Wald, Chaim M. Bell, Jeffrey Perl
Journal: Journal of the American Society of Nephrology (2014)

Novel oral anticoagulants (NOACs) (rivaroxaban, dabigatran, apixaban) have been approved by international regulatory agencies to treat atrial fibrillation and venous thromboembolism in patients with kidney dysfunction. However, altered metabolism of these drugs in the setting of impaired kidney function may subject patients with CKD to alterations in their efficacy and a higher risk of bleeding. This article examined the efficacy and safety of the NOACs versus vitamin K antagonists (VKAs) for atrial fibrillation and venous thromboembolism in patients with CKD. A systematic review and meta-analyses of randomized controlled trials were conducted to estimate relative risk (RR) with 95% confidence interval (95% CIs) using a random-effects model. MEDLINE, Embase, and the Cochrane Library were searched to identify articles published up to March 2013. We selected published randomized controlled trials of NOACs compared with VKAs of at least 4 weeks' duration that enrolled patients with CKD (defined as creatinine clearance of 30-50 ml/min) and reported data on comparative efficacy and bleeding events. Eight randomized controlled trials were eligible. There was no significant difference in the primary efficacy outcomes of stroke and systemic thromboembolism (four trials, 9693 participants; RR, 0.64 [95% CI, 0.39 to 1.04]) and recurrent thromboembolism or thromboembolism-related death (four trials, 891 participants; RR, 0.97 [95% CI, 0.43 to 2.15]) with NOACs versus VKAs. The risk of major bleeding or the combined endpoint of major bleeding or clinically relevant nonmajor bleeding (primary safety outcome) (eight trials, 10,616 participants; RR 0.89 [95% CI, 0.68 to 1.16]) was similar between the groups. The use of NOACs in select patients with CKD demonstrates efficacy and safety similar to those with VKAs. Proactive postmarketing surveillance and further studies are pivotal to further define the rational use of these agents.
Benign Duodeno-colonic Fistula
Authors: G. N. Chandler, A. J. Longmore
Journal: Gut (1960)

Two cases of benign duodeno-colic fistula are described. In the first, no cause was evident, but complete cure of an illness characterized by fatty diarrhoea, loss of weight, anaemia, and osteomalacia followed surgical repair. In the second patient cure was spontaneous after a peri-duodenal abscess from a perforated post-bulbar duodenal ulcer discharged into the hepatic flexure of the colon.
SPECIFIC IMMUNE RESPONSE GENES OF THE GUINEA PIG
Authors: Harry G. Bluestein, Ira Green, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1971)

The lymph node cells from all L-glutamic acid and L-tyrosine (GT) responder random-bred guinea pigs were susceptible to lysis by strain 2 anti-strain 13 isoantisera in the presence of complement. These same antisera were cytolytic for lymph node cells of only some of the GT nonresponder animals. However, after absorption with cells, from a nonresponder guinea pig, susceptible to lysis, the anti-strain 13 antisera were no longer able to lyse cells from any GT nonresponder guinea pigs while retaining a large measure of their cytolytic activity for cells of all GT responder guinea pigs. Thus, at least two major strain 13 histocompatibility specificities are expressed on the cells of random-bred guinea pigs. The genetic locus controlling the expression of only one of those strain 13 histocompatibility specificities is linked to the GT immune response gene.
Genetic Testing in Li-Fraumeni Syndrome: Uptake and Psychosocial Consequences
Authors: Chantal R.M. Lammens, Neil K. Aaronson, Anja Wagner, Rolf H. Sijmons, Margreet G.E.M. Ausems, Annette H. J.T. Vriends, Mariëlle W.G. Ruijs, Theo A.M. van Os, Liesbeth Spruijt, Encarna B. Gómez García, Irma Kluijt, Tanja Nagtegaal, Senno Verhoef, Eveline M.A. Bleiker
Journal: Journal of Clinical Oncology (2010)

Li-Fraumeni syndrome (LFS) is a hereditary cancer syndrome, characterized by a high risk of developing cancer at various sites and ages. To date, limited clinical benefits of genetic testing for LFS have been demonstrated, and there are concerns about the potential adverse psychosocial impact of genetic testing for LFS. In this study, we evaluated the uptake of genetic testing and the psychosocial impact of undergoing or not undergoing a genetic test for LFS.In total, 18 families with a p53 germline mutation in the Netherlands were identified. Eligible family members were invited to complete a self-report questionnaire assessing motives for undergoing or not undergoing genetic testing, LFS-related distress and worries, and health-related quality of life.Uptake of presymptomatic testing was 55% (65 of 119). Of the total group, 23% reported clinically relevant levels of LFS-related distress. Carriers were not significantly more distressed than noncarriers or than those with a 50% risk who did not undergo genetic testing. Those with a lack of social support were more prone to report clinically relevant levels of distress (odds ratio, 1.3; 95% CI, 1.0 to 1.5).Although preventive and treatment options for LFS are limited, more than half of the family members from known LFS families choose to undergo presymptomatic testing. An unfavorable genetic test result, in general, does not cause adverse psychological effects. Nonetheless, it is important to note that a substantial proportion of individuals, irrespective of their carrier status, exhibit clinically relevant levels of distress which warrant psychological support.
Osteotropic Therapy via Targeted Layer‐by‐Layer Nanoparticles
Authors: Stephen W. Morton, Nisarg J. Shah, Mohiuddin A. Quadir, Zhou J. Deng, Zhiyong Poon, Paula T. Hammond
Journal: Advanced Healthcare Materials (2013)

Current treatment options for debilitating bone diseases such as osteosarcoma, osteoporosis, and bone metastatic cancer are suboptimal and have low efficacy. New treatment options for these pathologies require targeted therapy that maximizes exposure to the diseased tissue and minimizes off‐target side effects. This work investigates an approach for generating functional and targeted drug carriers specifically for treating primary osteosarcoma, a disease in which recurrence is common and the cure rate has remained around 20%. This approach utilizes the modularity of Layer‐by‐Layer (LbL) assembly to generate tissue‐specific drug carriers for systemic administration. This is accomplished via surface modification of drug‐loaded nanoparticles with an aqueous polyelectrolyte, poly(acrylic acid) (PAA), side‐chain functionalized with alendronate, a potent clinically used bisphosphonate. Nanoparticles coated with PAA‐alendronate are observed to bind and internalize rapidly in human osteosarcoma 143B cells. Encapsulation of doxorubicin, a front‐line chemotherapeutic, in an LbL‐targeted liposome demonstrates potent toxicity in vitro. Active targeting of 143B xenografts in NCR nude mice with the LbL‐targeted doxorubicin liposomes promotes enhanced, prolonged tumor accumulation and significantly improved efficacy. This report represents a tunable approach towards the synthesis of drug carriers, in which LbL enables surface modification of nanoparticles for tissue‐specific targeting and treatment.
Effect of Dutasteride on the Risk of Prostate Cancer
Authors: Gerald L. Andriole, David G. Bostwick, Otis W. Brawley, Leonard G. Gomella, Michael Marberger, Francesco Montorsi, Curtis A. Pettaway, Teuvo L. Tammela, Claudio Teloken, Donald J. Tindall, Matthew C. Somerville, Timothy H. Wilson, Ivy L. Fowler, Roger S. Rittmaster
Journal: New England Journal of Medicine (2010)

We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease.
The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome
Authors: S.K. Blank, C.R. McCartney, J.C. Marshall
Journal: Human Reproduction Update (2006)

Polycystic ovary syndrome (PCOS) is a common clinical disorder characterized by ovulatory dysfunction and hyperandrogenaemia. A neuroendocrine hallmark of PCOS is persistently rapid LH (GnRH) pulsatility, which favours pituitary synthesis of LH over that of FSH and contributes to the increased LH concentrations and LH : FSH ratios typical of PCOS. Inadequate FSH levels contribute to impaired follicular development, whereas elevated LH levels augment ovarian androgen production. Whereas luteal phase elevations in progesterone normally slow GnRH pulse frequency, women with PCOS do not experience normal progesterone-mediated slowing, due in part to impaired hypothalamic progesterone sensitivity. This reduction in hypothalamic progesterone sensitivity appears to be mediated by elevated androgens because sensitivity can be restored with the androgen receptor blocker flutamide. The ovulatory and hormonal abnormalities associated with PCOS generally present during puberty, typically associated with hyperandrogenaemia. Along with elevated LH concentration and pulsatility, some girls with hyperandrogenaemia have impaired hypothalamic progesterone sensitivity similar to that seen in adult women with PCOS. We propose that peripubertal hyperandrogenaemia may lead to persistently rapid GnRH pulse frequency via impaired hypothalamic feedback inhibition. The subsequent abnormalities in gonadotropin secretion, androgen production and ovulatory function may support progression towards the adult PCOS phenotype.
Leaders Increase Activity After Mammography Summit
Authors: Cori Vanchieri, Linda Baute
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Leaders Increase Activity After Mammography Summit Get access Cori Vanchieri, Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda Baute Linda Baute Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 1, 3 January 1990, Pages 12–13, https://doi.org/10.1093/jnci/82.1.12 Published: 03 January 1990
Maximal inspiratory and expiratory mouth pressures in children with mild bronchial asthma
Authors: Jakub Zatloukal, Katerina Neumannova, Jana Rydlova, Dana Dvorakova
Journal: European Respiratory Journal (2012)

Introduction  Decreased respiratory muscle strength can lead to a higher respiratory effort that reflects on a quality of life in patients with bronchial asthma (BA).  Aim  To compare maximal inspiratory (MIP) and expiratory (MEP) mouth pressures in healthy children and children with BA undergoing a pulmonary rehabilitation programme (PRP).  Methods  The examined group (E) consisted of 108 children with mild BA (aged 11.9±2.6 years), who underwent a 4-week PRP which included respiratory physiotherapy and physical activity training. The MIP and MEP assessment was performed at the baseline and after the PRP. The control group (C) consisted of 208 healthy children (aged 11.9±2.0 years) without any treatment.  Results  The MIP and MEP values of BA children were about the same or lower than those of C group at the beginning of the PRP, but there were no significant differences among the groups (Tab. 1). A significant improvement of MIP and MEP was observed in BA children after the PRP (Tab. 2) and furthermore the MIP and MEP values were higher than values in C group (Tab. 1).  Conclusion  The MIP and MEP values in children with mild BA are not significantly lower than values of healthy children.  Study was supported by grants of the Palacky University – FTK_2011_010; FTK_2012:023.