tbuckley/cabot-search huggingface dataset:
Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds
Authors: Mark J. Niciu, Ioline D. Henter, David A. Luckenbaugh, Carlos A. Zarate, Dennis S. Charney
Journal: The Annual Review of Pharmacology and Toxicology (2014)

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine's antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine's adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine's antidepressant effects.
Secondary cytoreduction for ovarian cancer following cisplatin therapy.
Authors: R A Segna, P R Dottino, J P Mandeli, K Konsker, C J Cohen
Journal: Journal of Clinical Oncology (1993)

This study was undertaken to evaluate the efficacy of secondary surgical cytoreduction in the management of ovarian cancer.The cases of 100 patients with recurrent or progressive epithelial ovarian cancer whose initial treatment had been cytoreduction followed by cytotoxic therapy with a cisplatin-based regimen were reviewed. All 100 patients underwent surgery, after recurrence or progression was documented preoperatively, by gynecologic oncologists at the Mount Sinai Medical Center, New York, NY, between 1980 and 1991 with the intention of performing radical tumor reduction.Sixty-one patients had a secondary cytoreduction that left residual disease less than 2 cm in diameter. The median survival, determined from the date of the secondary cytoreduction to the date of death or last follow-up, is 27.1 months in the optimally treated group and 9.0 months for the 39 patients whose surgery was suboptimal (P = .0001). Other variables associated with statistically significant longer survival, and a significantly higher probability of achieving a successful secondary cytoreduction, included age < or = 55 years at the time of secondary cytoreduction, interval from initial diagnosis to secondary cytoreduction of more than 12 months, residual disease at initial staging laparotomy of less than 2 cm, and a complete clinical response to a cisplatin-based front-line regimen. Multivariate analysis confirms the survival benefit provided by a successful secondary cytoreduction when adjusted for the above variables. There was one postoperative mortality. Ten percent of the successfully cytoreduced patients and 18% of the unsuccessfully cytoreduced patients experienced some degree of postoperative morbidity.These data justify the performance of secondary cytoreductive surgery for patients who develop gross recurrent or progressive ovarian cancer following cisplatin therapy.
Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations
Authors: E Baraldi
Journal: Thorax (2003)

<b>Background:</b> Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. <b>Methods:</b> Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE<sub>NO</sub>) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE<sub>NO</sub> was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. <b>Results:</b> Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4–15.6); 8-isoprostane, 12.0 pg/ml (9.4–29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0–5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1–3.0), p&lt;0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9–8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4–11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p&lt;0.001). FE<sub>NO</sub> levels, which fell significantly after prednisone treatment (p&lt;0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. <b>Conclusion:</b> After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.
Effect of weight loss on upper airway size and facial fat in men with obstructive sleep apnoea
Authors: K. Sutherland, R. W. W. Lee, C. L. Phillips, G. Dungan, B. J. Yee, J. S. Magnussen, R. R. Grunstein, P. A. Cistulli
Journal: Thorax (2011)

Obstructive sleep apnoea (OSA) is commonly associated with obesity and can be improved by weight loss. Changes in upper airway size related to regional fat loss may mediate the improvement in OSA. This study aimed to assess changes in upper airway size and regional facial and abdominal fat with weight loss and their association with OSA improvement.Middle-aged obese men with moderate-to-severe OSA underwent a 24-week sibutramine-assisted weight loss trial. Polysomnography and CT of the head and neck were performed at baseline and 24 weeks. The upper airway lumen and facial and parapharyngeal fat were measured with image analysis software.Post-intervention there was a significant reduction in weight (-7.8±4.2 kg, p<0.001) and apnoea-hypopnoea index (AHI) (-15.9±20.5 events/h, p<0.001). Velopharyngeal airway volume significantly increased from baseline (5.3±0.4 to 6.3±0.3 cm(3), p<0.01) and facial and paraphayngeal fat volume significantly reduced. A reduction in upper airway length was associated with improvement in AHI (r=0.385, p=0.005). The variance in AHI improvement was best explained by changes in upper airway length and visceral abdominal fat (R(2)=0.31, p=0.004).Weight loss increases velopharyngeal airway volume, but changes in upper airway length appear to have a greater influence on the reduction in apnoea frequency. Inter-individual variability in the effects of weight loss on OSA severity cannot be explained in terms of changes in upper airway structure and local fat deposition alone.
Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors
Authors: J.T. Hartmann, C.R. Nichols, J.-P. Droz, A. Horwich, A. Gerl, S.D. Fossa, J. Beyer, J. Pont, L. Kanz, L. Einhorn, C. Bokemeyer
Journal: Annals of Oncology (2002)
Esophageal Sphincter Device for Gastroesophageal Reflux Disease
Authors: Robert A. Ganz, Jeffrey H. Peters, Santiago Horgan, Willem A. Bemelman, Christy M. Dunst, Steven A. Edmundowicz, John C. Lipham, James D. Luketich, W. Scott Melvin, Brant K. Oelschlager, Steven C. Schlack-Haerer, C. Daniel Smith, Christopher C. Smith, Dan Dunn, Paul A. Taiganides
Journal: New England Journal of Medicine (2013)

Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter.We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported.The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed.In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.).
Reducing psychotropic drugs reduces falls in elderly people
Authors: J W Cooper
Journal: BMJ (2001)

In Editor's choice of 5 May the editor noted that AIDS is now a regular feature in the BMJ, and asks what health issues are missing that may later come to dominate the journal in 20 years' time.1 One potential candidate is road traffic crashes.By 2020 road traffic crashes are estimated to move from ninth to third in the world disease burden ranking, as measured in disability adjusted life years, and will be in second place in developing countries.2But, although road traffic crashes are a potential candidate in terms of disease burden, whether the BMJ will feature research relevant to this problem is far from assured.In comparison with the burden of disability, funding for research on road traffic crashes (prevention and treatment) is less than for almost any other cause of human misery.3Traffic crashes predominantly affect poor people.The million deaths and the 10 million permanent disabilities resulting from road traffic crashes are largely seen as the collateral damage in our car based transportation system.Who is setting the agenda on this issue?
Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal human microglia, astrocytes, and glioma cells
Authors: Grace H.-F. Chang, Nicholas M. Barbaro, Russell O. Pieper
Journal: Neuro-Oncology (2000)

Apoptotic cells display signals that trigger phagocytic removal by macrophages or neighboring cells. To better understand the signals triggering phagocytosis of apoptotic glioma cells, and to identify the cells that might be involved in the phagocytic process, U-251 MG glioma cells were made apoptotic by etoposide (25 microg/ml) treatment and were incubated with normal human astrocytes (NHA), glioma cells, or microglia. Extent of phagocytosis was assessed by an in vitro phagocytosis assay. After 3 h of incubation with apoptotic cells, phagocytes tested were washed to remove nonengulfed cells, then fixed, stained, and counted to determine phagocytosis index (PI). NHA, glioma cells, and microglia all phagocytosed apoptotic, but not nonapoptotic, glioma cells. Microglia, however, had a PI approximately 4-fold higher than did either NHA or glioma cells. Binding of phosphatidylserine (PS) on apoptotic glioma cell membranes by annexin-V inhibited phagocytosis by 90% in both microglia and NHA. The activity of an enzyme (scramblase) that moves PS from the inner cell membrane to the outer cell membrane was also increased in apoptotic glioma cells. These results suggest that a variety of cells present in and near gliomas in vivo can remove glioma cells in a PS-dependent scramblase-mediated fashion. Manipulation of scramblase and/or PS exposure in glioma cells may therefore be a means of triggering phagocytic removal of glioma cells.
Enzymes of heme metabolism is the kidney. Regulation by trace metals which do not form heme complexes
Authors: MD Maines, A Kappas
Journal: The Journal of Experimental Medicine (1977)

The in vivo regulation by metal ions of the enzymes of heme metabolism in kidney-particularly of ALAS, the rate-limiting enzyme in heine formation- was investigated. Ni(2+) and Pt(4+), metals which do not enzymatically form metalloporphyrins, were found to regulate ALAS in kidney as they do in liver. The pattern of this regulation was generally similar to that observed with heme and metal ions in liver, i.e., a late increase in enzyme activity after an early period in which ALAS activity was unaltered or inhibited. The metals did not interact with the enzyme in vitro to alter its activity. In this study no direct reciprocal relationship between ALAS activity and total cellular heine content was demonstrated. The metal ions, particularly Pt(4+), also altered the activity of other enzymes of heme biosynthesis in kidney. Pt(4+) severely inhibited the activity of ALAD and UROS. Ni(2+) and Pt(4+) were potent inducers of heme oxygenase, the initial and rate-limiting enzyme in heine degradation. It is proposed that the physiological regulation of ALAS is mediated through the action of metal ions, rather than by the cellular content of heine, and that the regulation of ALAS by heine reflects the action of the central metal ion of heme rather than that of the entire metalloporphyrin complex. In this proposed mechanism for metal ion regulation of ALAS, the tetrapyrrole moiety of heine is considered to function principally as an efficient carrier of metal to the regulatory site for ALAS production, inasmuch as the tetrapyrrole ring itself has been shown in earlier studies not to have any effect on ALAS activity. The production of heine oxygenase is believed to be similarly regulated.
Tissue expression of Squamous Cellular Carcinoma Antigen (SCCA) is inversely correlated to tumor size in HCC
Authors: Paolo Trerotoli, Emilia Fransvea, Umberto Angelotti, Giovanni Antonaci, Luigi Lupo, Antonio Mazzocca, Anita Mangia, Salvatore Antonaci, Gianluigi Giannelli
Journal: Molecular Cancer (2009)

Abstract Background This study aimed to investigate squamous cellular carcinoma antigen (SCCA) in serum and in tumoral and paired peritumoral tissues. We studied 27 patients with liver cirrhosis (LC) and 55 with HCC: 20 with a single nodule &lt; 3 cm (s-HCC) and 35 with a single nodule &gt; 3 cm or multifocal (l-HCC). Methods Serum SCCA was measured by the ELISA kit, and in frozen tissues by immunohistochemistry, quantified with appropriate imaging analysis software and expressed in square microns. Continuous variables are reported as means and 95% confidence intervals. Comparisons between independent groups were performed with a generalized linear model and Tukey grouping. Pearson's correlation coefficients were determined to evaluate relations between markers. Qualitative variables were summarized as count and percentage. Statistical significance was set at p-value &lt; 0.05. Results Serum SCCA values in LC patients were 0.41 (0.31–0.55) ng/ml and statistically different from both HCC groups: 1.6 (1.0–2.6) ng/ml in s-HCC, 2.2 (1.28–2.74) ng/ml in l-HCC. SCCA in hepatic tissue was 263.8 (176.6–394.01) μm 2 in LC patients, statistically different from values in s-HCC: 1163.2 (863.6–1566.8) μm 2 and l-HCC: 625.8 (534.5–732.6). All pairwise comparisons between groups yielded statistically significant differences. Tumoral SCCA resulted linearly related with nodule size, showing a statistically significant inverse relation between the two variables (b = -0.099, p = 0.024). Conclusion There was no statistically significant correlation between tissue and serum levels of SCCA. The significantly stronger expression of SCCA in smaller compared to larger HCC could be important for early HCC detection. However, the increased expression in peritumoral tissue could affect the significance of serological detection.
Intralesional Injection of<i>Mycobacterium w</i>Vaccine vs Imiquimod, 5%, Cream in Patients With Anogenital Warts
Authors: Pankaj Kumar, Lalit Dar, Shashi Saldiwal, Sangeeta Varma, Aashish datt Upadhyay, Deepti Talwar, Vinod Kumar Sharma, Kaushal Kumar Verma, Sada Nand Dwivedi, Rama Raj, Somesh Gupta
Journal: JAMA Dermatology (2014)

IMPORTANCEIntralesional antigen therapy has been used in the treatment of anogenital warts (AGWs), but it has not been compared with existing therapies.Evidence of its efficacy is not strong.OBJECTIVE To compare the efficacy and safety of intralesional Mycobacterium w (Mw) vaccine with that of imiquimod, 5%, cream in the treatment of AGWs, as well as changes in human papillomavirus (HPV)-6 and HPV-11 viral loads. DESIGN, SETTING, AND PARTICIPANTSA double-blind randomized clinical trial was conducted in New Delhi, India, between February 2009 and July 2012 and included a 3-month follow-up.Of 159 patients with AGWs who were screened, 89 were randomized.INTERVENTIONS Patients received either imiquimod, 5%, cream and an intralesional vehicle (imiquimod group: 44 patients) or vehicle cream and intralesional Mw vaccine (Mw group: 45 patients). MAIN OUTCOMES AND MEASURESThe primary end point was complete clinical remission of visible AGWs.Secondary measures included the percentage of reduction in the surface area of AGWs and viral load for HPV-6 and HPV-11.Viral load was measured by real-time quantitative polymerase chain reaction. RESULTSIn the intention-to-treat analysis, 59% (n = 26) of the patients in the imiquimod group and 67% (n = 30) of those in the Mw group had complete resolution (P = .52).Eighteen HPV genotypes, including high-risk genotypes, were detected, with no significant differences between the treatment groups (all P > .05).There was a significant decline in the mean viral loads of HPV-6 (from 0.011 × 10 8 to 0.00000154 × 10 8 copies/mg of tissue; P = .003)and HPV-11 (from 0.121 × 10 8 to 0.017 × 10 8 copies/mg of tissue; P = .03)after treatment in the Mw group but only in the viral load of HPV-6 (from 1.41 × 10 8 to 0.004 × 10 8 copies/mg of tissue; P = .01)in the imiquimod group.There was no recurrence of AGWs in patients with complete clearance at the 3-month follow-up and no serious adverse events.CONCLUSIONS AND RELEVANCE Imiquimod, 5%, and the Mw vaccine were equally effective in achieving clinical and virologic clearance for HPV-6.A significant decline in the HPV-11 viral load was achieved only with the Mw vaccine.Efficacy and safety of intralesional Mw vaccine is comparable to that of imiquimod, 5%, in treatment of AGWs.
Prevalence of HBV precore/core promoter variants in the United States
Authors: Chi-Jen Chu, Emmet B. Keeffe, Steven-Huy Han, Robert P. Perrillo, Albert D. Min, Consuelo Soldevila-Pico, William Carey, Robert S. Brown, Velimir A. Luketic, Norah Terrault, Anna S.F. Lok
Journal: Hepatology (2003)

Variants in the precore (G 1896 A) and core promoter (A 1762 T, G 1764 A) regions of hepatitis B virus (HBV) may be related to serum HBV DNA levels and severity of liver disease. The aims of this nationwide study were to determine the prevalence of HBV precore/core promoter variants in the United States and the association between these variants and patient demographics, HBV genotypes, serum HBV DNA level, and severity of liver disease. A total of 694 consecutive chronic HBV–infected patients seen in 17 U.S. liver centers during a 1–year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotypes as well as precore and core promoter variants by line–probe assays. Quantitative HBV DNA levels were determined using Cobas Amplicor HBV Monitor kits. Precore and core promoter variants were found in 27% and 44% of patients with chronic HBV infection in the United States. Precore and core promoter variants were more common in hepatitis B e antigen (HBeAg)–negative than in HBeAg–positive patients (precore, 38% vs. 9%; core promoter, 51% vs. 36%; respectively, P &lt; .001). The prevalence of these variants was related to ethnicity, place of birth, and HBV genotypes. Patients with core promoter variants were more likely to have hepatic decompensation. Precore and/or core promoter variants were associated with higher serum HBV DNA levels in HBeAg–negative but not in HBeAg–positive patients. In conclusion, HBV precore and core promoter variants are not rare in the United States. Physicians should be aware of the existence of HBV precore and core promoter variants and the clinical condition of “HBeAg–negative chronic hepatitis.”
GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response
Authors: Nicolas Cohen, Enguerran Mouly, Haifa Hamdi, Marie-Christine Maillot, Marc Pallardy, Véronique Godot, Francis Capel, Axel Balian, Sylvie Naveau, Pierre Galanaud, François M. Lemoine, Dominique Emilie
Journal: Blood (2005)
Relations between synovial fluid and serum concentrations of osteocalcin and other markers of joint tissue turnover in the knee joint compared with peripheral blood
Authors: C Salisbury, M Sharif
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To determine if osteocalcin (OC) is locally produced in the joint and to study the relation between markers of bone, cartilage, and synovial tissue turnover. <h3>METHODS</h3> The concentrations of OC, keratan sulphate epitope (5D4), and hyaluronate (HA) were measured in paired serum and synovial fluid in 10 healthy volunteers and 15 patients with osteoarthritis (OA) and 16 with rheumatoid arthritis (RA). OC was measured with a commercial immunoradiometric assay and concentrations of 5D4 and HA were measured using enzyme linked immunosorbent inhibition assays. <h3>RESULTS</h3> Synovial fluid OC was found to be significantly lower than serum (p&lt; 0.001) in all patients and controls. Synovial fluid OC concentrations were directly correlated with serum concentrations (<i>r</i>=0.63, p&lt;0.001) and with age (<i>r</i> = 0.48, p&lt; 0.01). There were also some relations between OC, HA, and 5D4 in patients with OA and RA. The OC concentrations were directly correlated with HA (<i>r</i>=0.68, p&lt;0.01) in OA serum and there was a similar correlation in RA synovial fluid (<i>r</i>=0.69, p&lt;0.01). A weak negative correlation was found between OC and 5D4 in OA serum (<i>r</i>=−0.55, p=0.035) while a weak positive correlation was found in RA serum (<i>r</i>=0.53, p=0.034). <h3>CONCLUSIONS</h3> These results show that more OC is present in the circulation than in knee joint fluids suggesting that synovial fluid OC may be derived from the blood.