tbuckley/cabot-search huggingface dataset:
Immune response of neonates to oral poliomyelitis vaccine.
Authors: T J John
Journal: BMJ (1984)

Newborn children 1 to 6 weeks of age were given oral polio vaccines to see whether the age limit of 6-8 weeks for the current Indian immunization program could be reduced.  180 neonates received oral polio vaccines followed by 2nd and 3rd doses at 4 week intervals.  Breast feeding was delayed 30 minutes after vaccination.  In 139 infants tested after the 3rd dose the titers against type 1 2 or 3 polio virus expressed as percentage of seroconversion did not differ from those seen in groups of children aged 6-20 or 6-51 weeks of age.  Babies less than 1 week old were not tested because the literature suggests that their antibody response is inhibited.  These results show that maternal antibodies do not prevent local infection by poliovirus in the gut of infants as young as 1 week old.
Corticosteroid Therapy in IgA Nephropathy
Authors: Jicheng Lv, Damin Xu, Vlado Perkovic, Xinxin Ma, David W. Johnson, Mark Woodward, Adeera Levin, Hong Zhang, Haiyan Wang
Journal: Journal of the American Society of Nephrology (2012)

The benefits and risks of steroids for the treatment of IgA nephropathy remain uncertain. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for randomized, controlled trials of corticosteroid therapy for IgA nephropathy published between 1966 and March 2011. We identified nine relevant trials that included 536 patients who had urinary protein excretion >1 g/d and normal renal function. Forty-six (8.6%) of these patients developed a kidney failure event, defined as doubling of the serum creatinine/halving of the GFR or ESRD. Overall, steroid therapy was associated with a lower risk for kidney failure (relative risk, 0.32 [95% confidence interval [CI], 0.15–0.67]; P=0.002) and a reduction in proteinuria (weighted mean difference, −0.46 g/d [95% CI, −0.63 to −0.29 g/d]), with no evidence of heterogeneity in these outcomes. Subgroup analysis suggested that the dose modifies the effect of steroids for renal protection (P for heterogeneity=0.030): Relatively high-dose and short-term therapy (prednisone >30 mg/d or high-dose pulse intravenous methylprednisolone with duration ≤1 year) produced significant renal protection, whereas low-dose, long-term steroid use did not. Steroid therapy was associated with a 55% higher risk for adverse events. The quality of included studies was low, however, limiting the generalizability of the results. In conclusion, steroids appear to provide renal protection in patients with IgA nephropathy but increase the risk for adverse events. Reliably defining the efficacy and safety of steroids in IgA nephropathy requires a high-quality trial with a large sample size.
Promoting “Low T”
Authors: Stephen R. Braun
Journal: JAMA Internal Medicine (2013)

Despite progress in raising the level of transparency about funding, conflicts of interest, and ghostwriting, drug companies remain free to pursue subtle and, therefore, effective means of marketing. Continuing medical education programs and "consensus" panels continue to be funded by companies selling products directly tied to the messages being conveyed by the resulting "educational" materials. And patient education materials continue to be created that, while factually accurate, subtly shift attitudes by including only selected facts and/or omitting ideas that would undermine the funder's preferred paradigm.
Chlamydia trachomatis: impact on human reproduction
Authors: J Paavonen
Journal: Human Reproduction Update (1999)

Chlamydia trachomatis infections are the most prevalent bacterial sexually transmitted infections (STI) recognized throughout the world. Worldwide, the magnitude of morbidity associated with sexually transmitted chlamydial infections is enormous. C.trachomatis is a common cause of urethritis and cervicitis, and sequelae include pelvic inflammatory disease (PID), ectopic pregnancy, tubal factor infertility, epididymitis, proctitis and reactive arthritis. The sharp worldwide increase in the incidence of PID during the past two decades has led to the secondary epidemics of tubal factor infertility and ectopic pregnancy. Chlamydial PID is the most important preventable cause of infertility and adverse pregnancy outcome. Chlamydial infections, like STI in general, are primarily a woman's health care issue since the manifestations and consequences are more damaging to the reproductive health in women than in men. Based on the available evidence, approximately 20% of women with chlamydial lower genital tract infection will develop PID, approximately 4% develop chronic pelvic pain, 3% infertility, and 2% adverse pregnancy outcome. However, these estimates are based on relatively weak evidence. Research on the link between C.trachomatis and male aspects of infertility has been much more limited. Currently recommended treatment regimens include azithromycin in a single dose or doxycycline for 7 days. These therapies are highly efficacious. Timely management of sex partners is essential for decreasing the risk for re-infection. Immunopathogenesis of C.trachomatis infection is one of the main focal points of current research into Chlamydia. Chlamydial infection fills the general prerequisites for disease prevention by screening, i.e. chlamydial infections are highly prevalent, usually asymptomatic, are associated with significant morbidity, can be reliably diagnosed, and are treatable. Screening programmes for C.trachomatis will be of paramount importance in the prevention of long-term sequelae. The cost of screening is only a fraction of the health care costs incurred due to complications resulting from undiagnosed and untreated chlamydial infections. Current strategies to control C.trachomatis still largely depend on clinic-based screening of symptomatic patients, and have not been successful. The development of highly sensitive and specific nucleic acid amplification tests for the diagnosis of chlamydial infections has been an important advance in the ability to conduct population-based screening programmes to prevent complications. Thus, the case for screening is clearly made, but much detail remains to be worked out.
Parenthood in Survivors of Hodgkin Lymphoma: An EORTC-GELA General Population Case-Control Study
Authors: Marleen A.E. van der Kaaij, Natacha Heutte, Paul Meijnders, Edwige Abeilard-Lemoisson, Michele Spina, Lotte C. Moser, Anouk Allgeier, Bart Meulemans, Brice Dubois, Arnold H.M. Simons, Pieternella J. Lugtenburg, Berthe M.P. Aleman, Evert M. Noordijk, Christophe Fermé, José Thomas, Aspasia Stamatoullas, Christophe Fruchart, Pauline Brice, Isabelle Gaillard, Jeanette K. Doorduijn, Catherine Sebban, Wilma G.J.M. Smit, Serge Bologna, Judith M. Roesink, Francisca Ong, Marc P.E. André, John M.M. Raemaekers, Michel Henry-Amar, Hanneke C. Kluin-Nelemans
Journal: Journal of Clinical Oncology (2012)

Purpose We investigated the impact of Hodgkin lymphoma (HL) on parenthood, including factors influencing parenthood probability, by comparing long-term HL survivors with matched general population controls. Patients and Methods A Life Situation Questionnaire was sent to 3,604 survivors treated from 1964 to 2004 in successive clinical trials. Responders were matched with controls (1:3 or 4) for sex, country, education, and year of birth (10-year groups). Controls were given an artificial date of start of treatment equal to that of their matched case. The main end point was presence of biologic children after treatment, which was evaluated by using conditional logistic regression analysis. Logistic regression analysis was used to analyze factors influencing spontaneous post-treatment parenthood. Results In all, 1,654 French and Dutch survivors were matched with 6,414 controls. Median follow-up was 14 years (range, 5 to 44 years). After treatment, the odds ratio (OR) for having children was 0.77 (95% CI, 0.68 to 0.87; P &lt; .001) for survivors compared with controls. Of 898 survivors who were childless before treatment, 46.7% achieved post-treatment parenthood compared with 49.3% of 3,196 childless controls (OR, 0.87; P = .08). Among 756 survivors with children before treatment, 12.4% became parents after HL treatment compared with 22.2% of 3,218 controls with children before treatment (OR, 0.49; P &lt; .001). Treatment with alkylating agents, second-line therapy, and age older than 35 years at treatment appeared to reduce the chances of spontaneous post-treatment parenthood. Conclusion Survivors of HL had slightly but significantly fewer children after treatment than matched general population controls. The difference concerned only survivors who had children before treatment and appears to have more personal than biologic reasons. The chance of successful post-treatment parenthood was 76%.
Corrigendum to: Functional analysis of novel TBX5 T-box mutations associated with Holt-Oram syndrome
Authors: C. J. J. Boogerd, D. Dooijes, A. Ilgun, I. B. Mathijssen, R. Hordijk, I. M. B. H. van de Laar, P. Rump, H. E. Veenstra-Knol, A. F. M. Moorman, P. Barnett, A. V. Postma
Journal: Cardiovascular Research (2010)

[[ Cardiovascular Research, Volume 88, Issue 1, 1 October 2010, Pages 130–139; doi:101093/cvr/cvq178. ]][1]

The original version of this article was incorrect: Inge B. Mathijssen was not included as a co-author. The online version of the article has been corrected, but the print version remains
The shape of the distal femur: a palaeopathological comparison of eburnated and non-eburnated femora
Authors: L. Shepstone, J. Rogers, J. Kirwan, B. Silverman
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> To determine the difference in shape of the distal femur, viewed axially in two dimensions, between eburnated and non-eburnated femora. <h3>METHODS</h3> A comparison of 52 non-eburnated and 16 eburnated femora drawn from a large archeological skeletal population. Eburnation was taken to indicate late stage osteoarthritis. Shape variability, based on landmarks, was quantified using a principal components analysis after a Procrustes alignment. <h3>RESULTS</h3> A statistically significant difference was found between the two groups. This was with respect to the patellar groove and the shape of the medial condyle. The latter difference is consistent with bone remodelling as a knee stabilising mechanism. <h3>CONCLUSIONS</h3> Anatomical shape can be quantified using an uncomplicated statistical technique. It was used to quantify the shape of the distal femur and demonstrate shape differences associated with osteoarthritis of the knee.
A Multidose Study of Haloperidol Decanoate in the Maintenance Treatment of Schizophrenia
Authors: John M. Kane, John M. Davis, Nina Schooler, Stephen Marder, Daniel Casey, Benjamin Brauzer, Jim Mintz, Robert Conley
Journal: American Journal of Psychiatry (2002)

Maintenance medication is critical in the prevention of psychotic relapse and rehospitalization among patients with schizophrenia. Given potential adverse effects, identification of the minimum effective dose is clinically important.A multicenter, double-blind study was conducted to determine rates of symptomatic exacerbation and adverse effects in 105 outpatients with schizophrenia randomly assigned to four different fixed doses of haloperidol decanoate and treated for 1 year or until relapse. The doses used were 25, 50, 100, and 200 mg given intramuscularly once per month.Rates of symptomatic exacerbation were 15% in the 200-mg group, 23% with 100 mg, 25% with 50 mg, and 60% with 25 mg. No significant differences in outcome were found between the groups treated with 200, 100, and 50 mg. Among the patients who completed the trial with no symptomatic exacerbation, there were no differences between dose groups on measures of psychopathology at the final rating point.The results of this study suggest that the 200-mg/month dose of haloperidol decanoate is associated with the lowest rate of symptomatic exacerbation (15%) with minimal increased risk of adverse effects or subjective discomfort in comparison to 100 or 50 mg. At the same time, the rates of worsening with 100 mg (23%) and 50 mg (25%) were not significantly greater than that seen with 200 mg. These results provide some guidance as to effective dose ranges of haloperidol decanoate.
Antigen Inhalation Unmasks NK-2 Tachykinin Receptor–mediated Responses in Vagal Afferents
Authors: KIMBERLY A. MOORE, BRADLEY J. UNDEM, DANIEL WEINREICH
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The majority of airway sensory innervation originates from afferent neurons whose somata reside in vagal (nodose and jugular) ganglia. Using guinea pigs immunized with chick ovalbumin, we have discovered that airway inflammation provokes phenotypic changes in the tachykinin responsiveness of nodose neurons. Bath application of substance P (SP; 0.1 to 10 μ M) to nodose neurons isolated from guinea pigs with normal uninflamed airways did not elicit measurable changes in resting electrophysiological properties. In sharp contrast, 80% of nodose neurons isolated 24 h after in vivo aerosolized antigen challenge of the airway were depolarized by 100 nM SP. Inhalation of a nonantigenic protein did not evoke the expression of SP responses. Pharmacological analysis revealed that SP responses unmasked by airway inflammation were mediated by neurokinin-2 (NK-2) tachykinin receptors. There are several potential mechanisms for transduction of an “unmasking signal” from the inflamed airway to vagal afferent somata. The vagus nerve may relay the signal, either through anterograde transport and/or nerve impulse activity. Alternatively, a signal generated by airway inflammation may be carried by the circulation to the nodose ganglia. Unilateral vagotomy significantly reduced the percentage of SP-responsive neurons compared with intact controls, suggesting that the vagus nerve is required for unmasking of NK-2 responses. Moore KA, Undem BJ, Weinreich D. Antigen inhalation unmasks NK-2 tachykinin receptor–mediated responses in vagal afferents.
Association Between Tamsulosin and Serious Ophthalmic Adverse Events in Older Men Following Cataract Surgery
Authors: Chaim M. Bell
Journal: JAMA (2009)

Both benign prostatic hyperplasia (BPH) and cataract formation are common in older men. The alpha-adrenergic receptor blocker tamsulosin is frequently prescribed to treat BPH, and research suggests this drug may increase the intraoperative difficulty of cataract surgery. No studies have documented whether use of tamsulosin or other alpha-blocker drug therapies affect the risk of serious postoperative adverse events.To assess the risk of adverse events following cataract surgery in older men prescribed tamsulosin or other alpha-blocking drugs used to treat BPH.Nested case-control analysis of a population-based retrospective cohort study using linked health care databases from Ontario, Canada. We included all men aged 66 years or older who had cataract surgery between 2002 and 2007 (N = 96 128).A composite of procedures signifying retinal detachment, lost lens or lens fragment, or endophthalmitis occurring within 14 days after cataract surgery. The risk of these adverse events was compared between men treated with tamsulosin or other alpha-blockers and men with no exposure to these medications in the year prior to cataract surgery. We separately examined the association of drug exposure that was either recent (within the 14 days before surgery) or previous (15-365 days before surgery).Overall, 3550 patients (3.7%) in the cohort had recent exposure to tamsulosin and 7426 patients (7.7%) had recent exposure to other alpha-blockers. Two hundred eighty-four patients (0.3%) had an adverse event. We randomly matched 280 of the cases to 1102 controls according to their age, surgeon, and year of surgery. Adverse events were significantly more common among patients with recent tamsulosin exposure (7.5% vs 2.7%; adjusted odds ratio [OR], 2.33; 95% confidence interval [CI], 1.22-4.43) but were not associated with recent exposure to other alpha-blockers (7.5% vs 8.0%; adjusted OR, 0.91; 95% CI, 0.54-1.54) or to previous exposure to either tamsulosin (< or = 1.8% vs 1%; adjusted OR, 0.94; 95% CI, 0.27-3.34) or other alpha-blockers (2.9% vs 2.1%; adjusted OR, 1.08; 95% CI, 0.47-2.48). This corresponds to an estimated number needed to harm (NNH) of 255 (95% CI, 99-1666).Exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events. There were no significant associations with exposure to other alpha-blocker medications used to treat BPH.
The CX3C chemokine fractalkine in allergic asthma and rhinitis
Authors: Anne-Cécile Rimaniol, Stephen J. Till, Gilles Garcia, Francis Capel, Véronique Godot, Karl Balabanian, Ingrid Durand-Gasselin, Eva Maria Varga, Gerald Simonneau, Dominique Emilie, Stephen R. Durham, Marc Humbert
Journal: Journal of Allergy and Clinical Immunology (2003)
Stress Responsivity and HPA Axis Activity in Juveniles: Results From a Home-Based CO<sub>2</sub>Inhalation Study
Authors: Thomas A. Terleph, Rachel G. Klein, Roxann Roberson-Nay, Salvatore Mannuzza, John L. Moulton, Girma Woldehawariat, Mary Guardino, Daniel S. Pine
Journal: American Journal of Psychiatry (2006)

A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO(2)-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO(2) are associated with elevated cortisol levels in juvenile offspring.A total of 131 offspring (ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO(2) inhalation.Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO(2) predicted elevated cortisol levels in offspring.As in adults, anxiety response to CO(2) in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses.
Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis: comparison with psoriasis and undifferentiated inflammatory arthritis
Authors: P Y P C Ho, A Barton, J Worthington, D Plant, C E M Griffiths, H S Young, P Bradburn, W Thomson, A J Silman, I N Bruce
Journal: Annals of the Rheumatic Diseases (2007)

Tests of pulmonary function (FVC, FEV1, FEV 1%, and single breath CO diffusion), renal function (serum creatinine and BUN), liver function (serum ALT, AST, and ALKP) and a full haematological screen were performed on 27 paraquat spraymen (mean spraying time 5.3 years; mean individual annual quantity of paraquat handled, 67.2 kg as paraquat ion) and on two control groups. One of the control groups consisted of 24 general plantation workers with minimal exposure to paraquat arising from occasional work in recently sprayed areas, and the second consisted of 23 latex factory workers with no known occupational exposure to paraquat. The results showed no significant differences as a consequence of occupational exposure to paraquat. Long-term paraquat spraying at the concentrations used produced to quantifiable harmful effects on health as measured by the indices selected for this study.
Surgery is effective for rotator cuff and cruciate injuries
Authors: W. A. Wallace
Journal: BMJ (2011)

I respond to Spence on the basis of my experience as a consultant orthopaedic surgeon for the past 27 years, my position as professor of orthopaedic surgery for the past 26 years, and my interest in sports medicine for over 20 years.1 Spence obviously has considerable experience of both rotator cuff tears and anterior cruciate ligament (ACL) injuries when he says: “Sports medicine trials are of poor …
A Phase I Open Label Study of the Farnesyltransferase Inhibitor CP-609,754 in Patients with Advanced Malignant Tumors
Authors: Stacy L. Moulder, John J. Mahany, Richard Lush, Caio Rocha-Lima, Michael Langevin, Karen J. Ferrante, Lisa Michele Bartkowski, Shama M. Kajiji, Dennis A. Noe, Simone Paillet, Daniel M. Sullivan
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this phase I clinical trial was to determine the maximum-tolerated dose and toxicity of CP-609,754 in patients with solid tumors refractory to standard therapies, to determine the cellular effects of CP-609,754 on its molecular target (farnesyltransferase), and to determine the recommended phase II dose (RP2D) of this agent. Experimental Design: Consenting patients with adequate bone marrow, liver, and renal function were enrolled with an accelerated dose strategy with single-patient parallel cohorts in whom the drug was given orally either once or twice daily. Once a dose-limiting toxicity was encountered or two patients developed Common Toxicity Criteria ≥ grade 2 toxicities, a modified Fibonacci sequence was initiated. Blood samples were collected during cycle 1 for pharmacokinetic and pharmacodynamic analyses. Results: A total of 68 cycles of CP-609,754 was administered to 21 patients enrolled in this study. The dose escalation was from 20 mg once daily to 640 mg twice per day, and at the highest dose level, one of six patients developed a dose-limiting toxicity of grade 3 neuropathy. The drug was otherwise well tolerated, and the maximum-tolerated dose was not reached because of the large number of tablets that would have been required for additional dose escalation. Pharmacokinetic analyses showed a proportional increase in exposure with dose, rapid oral absorption, and a half-life of ∼3 hours. Pharmacodynamic results predict a 95% maximal inhibition of peripheral blood mononuclear cell farnesyltransferase activity 2 hours postdose, on average, with a dose of 400 mg twice per day of CP-609,754. Conclusions: On the basis of the safety findings and the pharmacokinetic and pharmacodynamic analyses, the RP2D of CP-609,754 is ≥640 mg twice per day.
N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation
Authors: Salvador Iborra, Manuel Ramos, David M. Arana, Silvia Lázaro, Francisco Aguilar, Eugenio Santos, Daniel López, Edgar Fernández-Malavé, Margarita Del Val
Journal: The Journal of Experimental Medicine (2013)

Signals from the TCR that specifically contribute to effector versus memory CD8+ T cell differentiation are poorly understood. Using mice and adoptively transferred T lymphocytes lacking the small GTPase N-ras, we found that N-ras–deficient CD8+ T cells differentiate efficiently into antiviral primary effectors but have a severe defect in generating protective memory cells. This defect was rescued, although only partly, by rapamycin-mediated inhibition of mammalian target of rapamycin (mTOR) in vivo. The memory defect correlated with a marked impairment in vitro and in vivo of the antigen-mediated early induction of T-box transcription factor Eomesodermin (Eomes), whereas T-bet was unaffected. Besides N-ras, early Eomes induction in vitro required phosphoinositide 3-kinase (PI3K)–AKT but not extracellular signal-regulated kinase (ERK) activation, and it was largely insensitive to rapamycin. Consistent with N-ras coupling Eomes to T cell memory, retrovirally enforced expression of Eomes in N-ras–deficient CD8+ T cells effectively rescued their memory differentiation. Thus, our study identifies a critical role for N-ras as a TCR-proximal regulator of Eomes for early determination of the CD8+ T cell memory fate.