tbuckley/cabot-search huggingface dataset:
Beneficial Antipsychotic Effects of Celecoxib Add-On Therapy Compared to Risperidone Alone in Schizophrenia
Authors: Norbert Müller, Michael Riedel, Constanze Scheppach, Bernd Brandstätter, Safet Sokullu, Karin Krampe, Markus Ulmschneider, Rolf R Engel, Hans-Jürgen Möller, Markus J Schwarz
Journal: American Journal of Psychiatry (2002)

Abnormalities in the immune system in schizophrenia have been described. However, important findings such as high levels of activating cytokines in the CSF and signs of CNS inflammation have been controversial. The authors conducted a trial of the new selective cyclooxygenase-2 inhibitor celecoxib, an immunomodulatory drug, in schizophrenic patients to evaluate its therapeutic effects.In a prospective, double-blind evaluation, 50 patients with an acute exacerbation of schizophrenia were randomly assigned to either risperidone plus celecoxib or risperidone plus placebo. After a washout period, 25 patients received 2-6 mg/day of risperidone plus placebo and 25 received risperidone plus 400 mg/day of celecoxib for 5 weeks. The treatment effect was calculated by analysis of covariance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or risperidone dose or plasma level.Over 5 weeks, both groups of patients showed significant improvement in scores on the Positive and Negative Syndrome Scale and on all subscales. However, the celecoxib group showed significantly greater improvement in the total score.Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug showed beneficial effects on schizophrenia symptoms indicates that immune dysfunction in schizophrenia is not just an epiphenomenon but is related to the pathomechanism of the disorder. However, a nonimmunological therapeutic effect of celecoxib mediated by the N-methyl-D-aspartic acid receptor has to be taken into account.
Mechanism of neutralization of influenza virus by secretory IgA is different from that of monomeric IgA or IgG.
Authors: H P Taylor, N J Dimmock
Journal: The Journal of Experimental Medicine (1985)

We have found that bile is a useful source of secretory IgA (scIgA) which can specifically neutralize influenza virus infectivity. Using purified scIgA, we compared the mechanism of neutralization with that mediated by IgA monomers (prepared from scIgA by differential reduction) and IgG. At 4 degrees C, scIgA prevented the attachment of neutralized virus, while neither monomeric IgA nor IgG had any affect on this process or on the subsequent stages of infection by which virion RNA accumulates in nuclei. At 25 and 37 degrees C, scIgA permitted the attachment of approximately half the neutralized virus, but the virus was not internalized. Clearly, the neutralization depends on the character of the antibody used. scIgA may act by steric hindrance (with attachment or penetration, depending on temperature), whereas IgA and IgG neutralize infectivity at a stage subsequent to accumulation of the virus genome in the nucleus.
Comparison of Health-Related Quality of Life 5 Years After SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial
Authors: Juanita Mary Crook, Alfonso Gomez-Iturriaga, Kris Wallace, Clement Ma, Sharon Fung, Shabbir Alibhai, Michael Jewett, Neil Fleshner
Journal: Journal of Clinical Oncology (2010)

The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy (RP) and brachytherapy (BT) closed after 2 years due to poor accrual. We report health-related quality of life (HRQOL) at a mean of 5.3 years for 168 trial-eligible men who either chose or were randomly assigned to RP or BT following a multidisciplinary educational session.After initial lack of accrual, a multidisciplinary educational session was introduced for eligible patients. In all, 263 men attended 47 sessions. Of those, 34 consented to random assignment, 62 chose RP, and 94 chose BT. Five years later, these 190 men underwent HRQOL evaluation by using the cancer-specific 50-item Expanded Prostate Cancer Index Composite, the Short Form 12 Physical Component Score, and Short Form 12 Mental Component Score. Response rate was 88.4%. The Wilcoxon rank sum test was used to compare summary scores between the two interventions.Of 168 survey responders, 60.7% had BT (9.5% randomly assigned) and 39.3% had RP (9.5% randomly assigned). Median age was 61.4 years for BT and 59.4 for RP (P = .05). Median follow-up was 5.2 years (range, 3.2 to 6.5 years). For BT versus RP, there was no difference in bowel or hormonal domains, but men treated with BT scored better in urinary (91.8 v 88.1; P = .02) and sexual (52.5 v 39.2; P = .001) domains, and in patient satisfaction (93.6 v 76.9; P < .001).Although treatment allocation was random in only 19%, all patients received identical information in a multidisciplinary setting before selecting RP, BT, or random assignment. HRQOL evaluated 3.2 to 6.5 years after treatment showed an advantage for BT in urinary and sexual domains and in patient satisfaction.
The Inner Life of Physicians and Care of the Seriously Ill
Authors: Diane E. Meier
Journal: JAMA (2001)

Seriously ill persons are emotionally vulnerable during the typically protracted course of an illness. Physicians respond to such patients' needs and emotions with emotions of their own, which may reflect a need to rescue the patient, a sense of failure and frustration when the patient's illness progresses, feelings of powerlessness against illness and its associated losses, grief, fear of becoming ill oneself, or a desire to separate from and avoid patients to escape these feelings. These emotions can affect both the quality of medical care and the physician's own sense of well-being, since unexamined emotions may also lead to physician distress, disengagement, burnout, and poor judgment. In this article, which is intended for the practicing, nonpsychiatric clinician, we describe a model for increasing physician self-awareness, which includes identifying and working with emotions that may affect patient care. Our approach is based on the standard medical model of risk factors, signs and symptoms, differential diagnosis, and intervention. Although it is normal to have feelings arising from the care of patients, physicians should take an active role in identifying and controlling those emotions.
The<i>ACTN3</i>R577X polymorphism in Russian endurance athletes
Authors: I I Ahmetov, A M Druzhevskaya, I V Astratenkova, D V Popov, O L Vinogradova, V A Rogozkin
Journal: British Journal of Sports Medicine (2008)

The functional 577R allele of the alpha-actinin-3 (ACTN3) gene has been reported to be associated with elite power athlete status, while the nonfunctional 577XX genotype (predicts an alpha-actinin-3 deficient phenotype) has been hypothesised as providing some sort of advantage for endurance athletes. In the present study, the distribution of ACTN3 genotypes and alleles in Russian endurance-oriented athletes were examined and association between ACTN3 genotypes and the competition results of rowers were sought.456 Russian endurance-oriented athletes of regional or national competitive standard were involved in the study. ACTN3 genotype and allele frequencies were compared with 1211 controls. The data from the Russian Cup Rowing Tournament were used to search for possible association between the ACTN3 genotype and the long-distance (approximately 6 km) rowing results of 54 athletes. DNA was extracted from mouthwash samples. Genotyping for the R577X variant was performed by PCR and restriction enzyme digestion.The frequencies of the ACTN3 577XX genotype (5.7% vs 14.5%; p<0.0001) and 577X allele (33.2% vs 39.0%; p = 0.0025) were significantly lower in endurance-oriented athletes compared with the controls, and none of the highly elite athletes had the 577XX genotype. Furthermore, male rowers with ACTN3 577RR genotype showed better results (1339 (11) s) in long-distance rowing than carriers of 577RX (1386 (12) s) or 577XX (1402 (10) s) genotypes (p = 0.016).Our data show that the ACTN3 577X allele is under-represented in Russian endurance athletes and is associated with the rowers' competition results.
Doxorubicin Administration by Continuous Infusion Is Not Cardioprotective: The Dana-Farber 91-01 Acute Lymphoblastic Leukemia Protocol
Authors: S. E. Lipshultz
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin. PATIENTS AND METHODS: In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m2 in 30-mg/m2 doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population. RESULTS: The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = −0.70 SD, P = .006; for continuous-infusion patients, median z score = −0.765, P = .005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ. CONCLUSION: Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored.
Full-term Abdominal Pregnancy with Survival of Mother and Child
Authors: M. L. Slotover
Journal: BMJ (1942)

Full-term Abdominal Pregnancy with Survival of Mother and ChildThe following is the history of this unusual case.M. M., aged 31, para 1 in 1931, which was a normal delivery of a stillborn child of 82 lb., came to the ante-natal clinic on June 30.1941.She was in good health and her pregnancy apparently normal.Her last period was early in November, 1940, and the approximate date for delivery was the middle of August, 1941.Her external pelvic measurements were normal, the urine contained nothing abnormal, and her blood pressure was 135/165.The presentation was 'a transverse with the head in the right iliac fossa.She had no past history of any disease, pelvic pain, or menstrual disorder.She was seen thrice at weekly intervals after her first visit, and each time the lie of the foetus was transverse with the head in the' right iliac fossa.She was otherwise normal on these occasions.She was admitted to hospital on July 26, at 10.45 a.m., complaining of pain in the right iliac fossa.There was no history of a "show."On examining her I made the following observations:Transverse lie, head to the right.Foetal heart sounds were heard and were normal.Vaginal examination revealed: (I) Cervix-external os patulous, internal os closed tightly.The
Active Vitamin D Treatment for Reduction of Residual Proteinuria
Authors: Martin H. de Borst, Reza Hajhosseiny, Hector Tamez, Julia Wenger, Ravi Thadhani, David J.A. Goldsmith
Journal: Journal of the American Society of Nephrology (2013)

Despite renin-angiotensin-aldosterone system blockade, which retards progression of CKD by reducing proteinuria, many patients with CKD have residual proteinuria, an independent risk factor for disease progression. We aimed to address whether active vitamin D analogs reduce residual proteinuria. We systematically searched for trials published between 1950 and September of 2012 in the Medline, Embase, and Cochrane Library databases. All randomized controlled trials of vitamin D analogs in patients with CKD that reported an effect on proteinuria with sample size≥50 were selected. Mean differences of proteinuria change over time and odds ratios for reaching ≥15% proteinuria decrease from baseline to last measurement were synthesized under a random effects model. From 907 citations retrieved, six studies (four studies with paricalcitol and two studies with calcitriol) providing data for 688 patients were included in the meta-analysis. Most patients (84%) used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker throughout the study. Active vitamin D analogs reduced proteinuria (weighted mean difference from baseline to last measurement was −16% [95% CI, −13% to −18%]) compared with controls (+6% [95% CI, 0% to +12%]; P<0.001). Proteinuria reduction was achieved more commonly in patients treated with an active vitamin D analog (204/390 patients) than control patients (86/298 patients; OR, 2.72 [95% CI, 1.82 to 4.07]; P<0.001). Thus, active vitamin D analogs may further reduce proteinuria in CKD patients in addition to current regimens. Future studies should address whether vitamin D therapy also retards progressive renal functional decline.
Safety of sentinel node biopsy in pregnant patients with breast cancer
Authors: O. Gentilini, M. Cremonesi, G. Trifirò, M. Ferrari, S.M. Baio, M. Caracciolo, A. Rossi, A. Smeets, V. Galimberti, A. Luini, G. Tosi, G. Paganelli
Journal: Annals of Oncology (2004)
CD81 (TAPA-1): A MOLECULE INVOLVED IN SIGNAL TRANSDUCTION AND CELL ADHESION IN THE IMMUNE SYSTEM
Authors: Shoshana Levy, Scott C. Todd, Holden T. Maecker
Journal: Annual Review of Immunology (1998)

CD81 (TAPA-1) is a widely expressed cell-surface protein involved in an astonishing variety of biologic responses. It has been cloned independently several times for different functional effects and is reported to influence adhesion, morphology, activation, proliferation, and differentiation of B, T, and other cells. On B cells CD81 is part of a complex with CD21, CD19, and Leu13. This complex reduces the threshold for B cell activation via the B cell receptor by bridging Ag specific recognition and CD21-mediated complement recognition. Similarly on T cells CD81 associates with CD4 and CD8 and provides a costimulatory signal with CD3. In fetal thymic organ culture, mAb to CD81 block maturation of CD4-CD8- thymocytes, and expression of CD81 on CHO cells endows those cells with the ability to support T cell maturation. However, CD81-deficient mice express normal numbers and subsets of T cells. These mice do exhibit diminished antibody responses to protein antigens. CD81 is also physically and functionally associated with several integrins. Anti-CD81 can activate integrin alpha 4 beta 1 (VLA-4) on B cells, facilitating their adhesion to tonsilar interfollicular stroma. Similarly, anti-CD81 can activate alpha L beta 2 (LFA-1) on human thymocytes. CD81 can also affect cognate B-T cell interactions because anti-CD81 increases IL-4 synthesis by T cells responding to antigen presented by B cells but not by monocytes. The tetraspanin superfamily (or TM4SF) includes CD81, CD9, CD37, CD53, CD63, CD82, CD151, and an increasing number of additional proteins. Like CD81, several tetraspanins are involved in cell adhesion, motility, and metastasis, as well as cell activation and signal transduction.
Analysis of the dinucleotide repeat polymorphism in the epidermal growth factor receptor (EGFR) gene in head and neck cancer patients
Authors: M.-C. Etienne-Grimaldi, S. Pereira, N. Magné, J.-L. Formento, M. Francoual, X. Fontana, F. Demard, O. Dassonville, G. Poissonnet, J. Santini, R.-J. Bensadoun, P. Szepetowski, G. Milano
Journal: Annals of Oncology (2005)
Effect of AIT in children including potential to prevent the development of asthma
Authors: E. Valovirta
Journal: Allergy (2011)

Allergy specific immunotherapy may alter the natural course of allergic disease. Thus, it is of significant importance, particularly in paediatric populations. Four studies using the grass allergy immunotherapy tablet (AIT) for allergic rhinoconjunctivitis in children showed good clinical outcomes and good safety profiles. Allergic rhinoconjunctivitis often precedes asthma, and treatment with specific immunotherapy has the potential to reduce the development of asthma in children suffering from rhinoconjunctivitis. Since Grazax® AIT has been shown to induce disease modification the prevention of asthma might be hypothesised. The GAP (Grazax® Asthma Prevention) trial is investigating the asthma preventive effect of standardised grass AIT in grass allergic children with rhinoconjunctivitis without asthma. The trial is a 5-year, multicentre, multinational, randomised, double-blind, placebo-controlled, prospective trial for children aged 5-12 years. In a few years, the results will show if grass AIT with Grazax® can prevent the development of asthma in children suffering from allergic rhinoconjunctivitis.
Eosinophilia in returning travellers and migrants from the tropics: UK recommendations for investigation and initial management
Authors: Anna M. Checkley, Peter L. Chiodini, David H. Dockrell, Imelda Bates, Guy E. Thwaites, Helen L. Booth, Michael Brown, Stephen G. Wright, Alison D. Grant, David C. Mabey, Christopher J.M. Whitty, Frances Sanderson
Journal: Journal of Infection (2009)
The Price We Pay for Progress: A Meta-Analysis of Harms of Newly Approved Anticancer Drugs
Authors: Saroj Niraula, Bostjan Seruga, Alberto Ocana, Tiffany Shao, Robyn Goldstein, Ian F. Tannock, Eitan Amir
Journal: Journal of Clinical Oncology (2012)

Registration of new anticancer drugs is usually based on results of randomized controlled trials (RCTs) showing improved efficacy when compared with standard therapy. There is relatively less emphasis on toxicity. In our study, we analyze serious toxicities of newly approved anticancer drugs reported in pivotal RCTs used for drug registration.We identified RCTs evaluating agents for the treatment of solid tumors approved by the US Food and Drug Administration between 2000 and 2010. Odds ratios (OR) and 95% CI were computed for three end points of safety and tolerability: treatment-related death, treatment-discontinuation related to toxicity, and grade 3 or 4 adverse events (AEs). These were then pooled in a meta-analysis. Correlations between these end points and the hazard ratios for overall survival (OS) and progression-free survival (PFS) were also assessed.Thirty-eight RCTs were analyzed. Compared with control groups, the odds of toxic death was greater for new agents (OR, 1.40; 95% CI, 1.15 to 1.70; P < .001) as were the odds of treatment-discontinuation (OR, 1.33; 95% CI, 1.22 to 1.45, P < .001). Grade 3 or 4 AEs (OR, 1.52; 95% CI, 1.35 to 1. 71; P < .001) were also more common with new agents, especially nonhematologic AEs such as diarrhea, skin reactions, and neuropathy. There were no significant correlations between safety end points and OS or PFS.New anticancer agents that lead to improvements in time-to-event end points also increase morbidity and treatment-related mortality. The balance between efficacy and toxicity may be less favorable in clinical practice because of selection of fewer patients with good performance status and limited comorbidities. Patients' baseline health characteristics should be considered when choosing therapy.
Disorders linked to insufficient androgen action in male children
Authors: C. Sultan
Journal: Human Reproduction Update (2001)

Virilization of the external genitalia in the male fetus requires testosterone and dihydrotestosterone (DHT), which is formed from testosterone by the action of the enzyme, 5alpha-reductase type 2 (5alphaR-2). Mediation of the effects of both testosterone and DHT requires a functional androgen receptor (AR) located in the cytoplasmic compartment of target cells. DHT (or testosterone) binding induces a conformational change which facilitates AR nuclear transport, phosphorylation and dimerization, ultimately regulating of the rate of transcription of androgen-dependent genes. Any event which impairs DHT formation (mutation within the 5alphaR-2 gene or 5alphaR-2 inhibitors) or normal function of the AR (mutation in the AR gene, antiandrogens) may result in insufficient androgen action in the male fetus and in subsequent undervirilization in the newborn. Hypospadias may be due to a defect in androgen action due to mutation of the 5alphaR-2 or of the AR gene. Mutation of unidentified genes is likely to underlie this displacement of the urethral meatus from the tip to the ventral side of the phallus. An aetiological role for environmental chemical products has been postulated, since ethnic as well as geographical differences in the incidence of hypospadias have been noted. Increasing evidence has been gathered indicating that widely used industrial and agricultural chemicals have deleterious effects on normal male sexual differentiation. Cryptorchidism and micropenis may represent an intersex phenotype, even if they are isolated. Aetiological factors include 5alphaR-2 gene mutation, AR gene mutation or environmental hormonal disruptors. In conclusion, several phenotypes have been attributed to insufficient androgen action during fetal life. Whereas mutations in the 5alphaR-2 gene and AR gene are natural, attention should be focused on environmental endocrine disruptors that are able to mimic steroid 5alpha-reductase deficiency or partial androgen insensitivity syndrome.
Xpert MTB/RIF assay for rapid detection of Mycobacterium tuberculosis and rifampicin resistance
Authors: Debajyoti Bhattacharyya, A. Agarwal, M.S. Barthwal, C.D.S. Katoch
Journal: European Respiratory Journal (2012)

Introduction: Xpert MTB/RIF is a novel molecular diagnostic point of care test for rapid detection of MTB and its susceptibility to rifampicin (RIF).

Objective: This study was performed to evaluate the performance of Xpert MTB/RIF assay in detection of MTB and resistance to rifampicin from sputum specimens taking positive culture for MTB and phenotypic resistance to rifampicin as reference standards.

Materials and Methods: 126 consecutive patients of pulmonary tuberculosis presenting to the hospital from December 2010 to January 2012 were enrolled for the study. Their sputum samples were subjected to concentrated ZN microscopy, culture on solid (LJ) and liquid (MGIT) media. All positive cultures were identified as MTB complex using SD TB Ag MPT 64 Rapid immunochromatographic test and indirect drug susceptibility testing performed by MGIT SIRE.

Result: Of the 126 cases included in the study, 83 were smear-positive and 43 were smear-negative. Of patients with culture positive samples, 20 of 126 (15.9%) were found to have multidrug resistance on indirect drug susceptibility testing with MGIT SIRE. With positive culture as the reference standard, MTB/RIF assay when done detected 98.7% of smear positive cases and 72.1% of smear negative cases. The test correctly identified all 20 of rifampicin resistant culture isolates and 105 of 106 rifampicin susceptible isolates for a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 99%, 95.2% and 100% respectively.

Conclusion: Xpert MTB/RIF assay is a reliable technique for rapid detection of Mycobacterium tuberculosis and Rifampicin resistance from pulmonary specimens.