tbuckley/cabot-search huggingface dataset:
Testosterone Concentration in Young Patients With Diabetes
Authors: Anil Chandel, Sandeep Dhindsa, Shehzad Topiwala, Ajay Chaudhuri, Paresh Dandona
Journal: Diabetes Care (2008)

We have previously shown that hypogonadotrophic hypogonadism is common in middle-aged patients with type 2, but not with type 1, diabetes. We have now investigated the total and free testosterone concentrations in young (aged 18-35 years) type 1 and type 2 diabetic patients.In this study carried out in a tertiary referral center, serum concentrations of total and free testosterone were measured in 38 type 1 diabetic (mean age 26.45 +/- 0.89 years) and 24 type 2 diabetic (mean age 27.87 +/- 0.97 years) subjects. The mean BMI of type 1 and type 2 diabetic patients was 27.41 +/- 1.18 and 38.55 +/- 2.04 kg/m(2), respectively (P < 0.001).The mean total testosterone concentration of type 1 and type 2 diabetic patients was 22.89 +/- 1.23 and 11.14 +/- 0.99 nmol/l, respectively (P < 0.001). The mean free testosterone concentration of type 1 and type 2 diabetic patients was 0.489 +/- 0.030 and 0.296 +/- 0.022 nmol/l, respectively (P < 0.001). Eight of 24 (33%) type 2 diabetic patients had subnormal free testosterone concentrations (<0.225 nmol/l). Using an age-based reference range, 14 of 24 (58%) type 2 diabetic patients had low free testosterone concentrations (<0.278 nmol/l). Three of 38 (8%) type 1 diabetic patients had free testosterone concentrations below the lower limit of normal (P = 0.02 when compared with type 2 diabetes). Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations in type 2 diabetic patients with low free testosterone concentrations were in the normal range and were similar to those in type 1 diabetic patients.Young type 2 diabetic patients have significantly lower plasma concentrations of total and free testosterone and inappropriately low LH and FSH concentrations with a very high prevalence of hypogonadotrophic hypogonadism, when compared with type 1 diabetic patients of a comparable age. The potential implications for their sexual and reproductive function during prime reproductive years are profound.
Expression of the α1-α6 collagen IV chains in the dermoepidermal junction during human foetal skin development: temporal and spatial expression of the α4 collagen IV chain in an early stage of development
Authors: None Tanaka, None Tajima, None Ishibashi, None Izumi, None Nishina, None Azuma, None Sado, None Ninomiya
Journal: British Journal of Dermatology (1998)

To study the expression of the α1–α6 chains of type IV collagen in the dermoepidermal junction (DEJ) during human foetal skin development, human foetal (10 and 20 weeks of gestation) and adult skin was immunostained with specific monoclonal antibodies to the α1–α6 chains of type IV collagen. Intense expression of the α4 chain and weak expression of the α2 and α6 chains were observed in the DEJ of 10 weeks gestational skin. In contrast, the α1, α2, α5 and α6 chains were detected in the DEJ of 20 weeks gestational and adult skin. Preferential expression of α4 during the early phase of development (10 weeks of gestation) may suggest a chain-specific regulatory mechanism for type IV collagen expression and its potential role in DEJ formation during development.
<i>VEGF</i> Polymorphisms and Survival in Early-Stage Non–Small-Cell Lung Cancer
Authors: Rebecca Suk Heist, Rihong Zhai, Geoffrey Liu, Wei Zhou, Xihong Lin, Li Su, Kofi Asomaning, Thomas J. Lynch, John C. Wain, David C. Christiani
Journal: Journal of Clinical Oncology (2008)

Purpose Polymorphisms in the VEGF gene have been identified that are believed to have functional activity. We hypothesized that such polymorphisms may affect survival outcomes among early-stage non—small-cell lung cancer (NSCLC) patients. Patients and Methods We evaluated the relationship between VEGF polymorphisms and overall survival (OS) among patients with early-stage NSCLC treated with surgical resection at Massachusetts General Hospital from 1992 to 2001. We specifically investigated the VEGF polymorphisms +936C&gt;T (rs3025039), −460T&gt;C ( rs833061 ), and +405G&gt;C (rs2010963). Analyses of genotype associations with survival outcomes were performed using Cox proportional hazards models, Kaplan-Meier methods, and the log-rank test. Results There were 462 patients and 237 deaths. Patients carrying the variant C allele of the VEGF +405G&gt;C polymorphism had significantly improved survival (crude hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.90; P = .006; adjusted HR = 0.70; 95% CI, 0.54 to 0.91; P = .008). Five-year OS for patients carrying the variant C allele of the VEGF +405G&gt;C polymorphism was 61% (95% CI, 54% to 67%) versus 51% (95% CI, 43% to 59%) for those who had the wild-type variant. There was a trend toward improved survival among patients carrying the variant T allele of the VEGF +936C&gt;T polymorphism (crude HR = 0.74; 95% CI, 0.53 to 1.03; P = .07; adjusted HR = 0.73; 95% CI, 0.52 to 1.03; P = .07). Moreover, patients with higher number of variant alleles of the +405G&gt;C and +936C&gt;T polymorphisms had better survival. There was no association found with the −460T&gt;C polymorphism. Conclusion Polymorphisms in VEGF may affect survival in early-stage lung cancer.
Phase 1 and Pharmacokinetic Study of Lexatumumab in Patients with Advanced Cancers
Authors: Ruth Plummer, Gerhardt Attard, Simon Pacey, Louise Li, Albiruni Razak, Rebecca Perrett, Mary Barrett, Ian Judson, Stan Kaye, Norma Lynn Fox, Wendy Halpern, Alfred Corey, Hilary Calvert, Johann de Bono
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To assess the safety and tolerability, pharmacokinetics, and early evidence of antitumor activity of escalating doses of lexatumumab (HGS-ETR2), a fully human agonistic monoclonal antibody which targets and activates the tumor necrosis factor–related apoptosis-inducing ligand receptor 2 (TRAIL-R2) in patients with advanced solid malignancies. Experimental Design: In this phase 1, open label study, patients with advanced solid malignancies were treated with escalating doses of lexatumumab administered i.v. over 30 to 120 min every 21 days. A cohort of four patients, which could be expanded to six patients, was studied at each dose level. The dose-limiting toxicity (DLT) dose was defined as the dose at which the incidence of DLT in the first two cycles was ≥33%. The maximum tolerated dose was defined as the highest dose at which &amp;lt;33% of subjects experienced DLT. The pharmacokinetics and immunogenicity of lexatumumab were also characterized. Tumor specimens from historical or current biopsies, when available, were stained for TRAIL-R2 using immunohistochemistry techniques. Results: Thirty-seven patients received 120 cycles of lexatumumab at doses ranging from 0.1 to 20 mg/kg every 21 days as of May 2006. The 20 mg/kg dose was identified as the DLT dose based on DLTs in three of seven patients treated with this dose; DLTs included asymptomatic elevations of serum amylase, transaminases, and bilirubin. The 10 mg/kg dose cohort was expanded to 12 patients and the 10 mg/kg dose was identified as the maximum tolerated dose. The mean (±SD) clearance and apparent terminal half-life values at the 10 mg/kg dose averaged 6.0 (2.9) mL/d/kg and 16.4 (10.9) days, respectively. Twelve patients had durable stable disease that lasted a median of 4.5 months, including three patients with sarcoma having prolonged stable disease (≥6.7 months). Immunohistochemistry for TRAIL-R2 showed specific staining in &amp;gt;10% of tumor cells for 16 of the 20 evaluable specimens submitted (80%). Conclusions: Lexatumumab was safe and well tolerated at doses up to and including 10 mg/kg every 21 days. Lexatumumab was associated with sustained stable disease in several patients. Pharmacokinetics were linear over the dose range studied, and consistent with a two-compartment model with first-order elimination from the central compartment. Additional evaluation of this novel apoptosis-inducing agent, particularly in combination with chemotherapy agents, is warranted and ongoing.
Minister admits government has not convinced public of the harms of excessive drinking
Authors: A. O'Dowd
Journal: BMJ (2011)

The government has failed so far to convince the general public of the dangers of excessive drinking of alcohol, MPs have heard.

The potentially serious harms from drinking are not accepted by the public in the same way that harms from smoking or being obese are, public health minister Anne Milton told MPs on the parliamentary science and technology committee.

The committee was holding an evidence session on 26 October as part of its inquiry into the evidence base for government alcohol guidance and how well guidelines are communicated to the public.

MPs asked whether the existing alcohol guidelines were there just as public information or if they were designed to change …
Paternal History of Asthma and Airway Responsiveness in Children with Asthma
Authors: Benjamin A. Raby, Kristel Van Steen, Juan C. Celedón, Augusto A. Litonjua, Christoph Lange, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Little is known regarding the relationship between parental history of asthma and subsequent airway hyperresponsiveness (AHR) in children with asthma. Objectives: We evaluated this relationship in 1,041 children with asthma participating in a randomized trial of antiinflammatory medications (the Childhood Asthma Management Program [CAMP]). Methods: Methacholine challenge testing was performed before treatment randomization and once per year over an average of 4.5 years postrandomization. Cross-sectional and longitudinal repeated measures analyses were performed to model the relationship between PC20 (the methacholine concentration causing a 20% fall in FEV1) with maternal, paternal, and joint parental histories of asthma. Models were adjusted for potential confounders. Measurements and Main Results: At baseline, AHR was strongly associated with a paternal history of asthma. Children with a paternal history of asthma demonstrated significantly greater AHR than those without such history (median logePC20, 0.84 vs. 1.13; p = 0.006). Although maternal history of asthma was not associated with AHR, children with two parents with asthma had greater AHR than those with no parents with asthma (median logePC20, 0.52 vs. 1.17; p = 0.0008). Longitudinal multivariate analysis of the relation between paternal history of asthma and AHR using repeated PC20 measurements over 44 months postrandomization confirmed a significant association between paternal history of asthma and AHR among children in CAMP. Conclusions: Our findings suggest that the genetic contribution of the father is associated with AHR, an important determinant of disease severity among children with asthma.
Transcription Poisoning by Topoisomerase I Is Controlled by Gene Length, Splice Sites, and miR-142-3p
Authors: Stéphanie Solier, Michael C. Ryan, Scott E. Martin, Sudhir Varma, Kurt W. Kohn, Hongfang Liu, Barry R. Zeeberg, Yves Pommier
Journal: Cancer Research (2013)

Topoisomerase I (Top1) relaxes DNA supercoiling by forming transient cleavage complexes (Top1cc) up- and downstream of transcription complexes. Top1cc can be trapped by carcinogenic and endogenous DNA lesions and by camptothecin, resulting in transcription blocks. Here, we undertook genome-wide analysis of camptothecin-treated cells at exon resolution. RNA samples from HCT116 and MCF7 cells were analyzed with the Affy Exon Array platform, allowing high-resolution mapping along 18,537 genes. Long genes that are highly expressed were the most susceptible to downregulation, whereas short genes were preferentially upregulated. Along the body of genes, downregulation was most important toward the 3'-end and increased with the number of exon-intron junctions. Ubiquitin and RNA degradation-related pathway genes were selectively downregulated. Parallel analysis of microRNA with the Agilent miRNA microarray platform revealed that miR-142-3p was highly induced by camptothecin. More than 10% of the downregulated genes were targets of this p53-dependent microRNA. Our study shows the profound impact of Top1cc on transcription elongation, especially at intron-exon junctions and on transcript stability by microRNA miR-142-3p upregulation.
Clinical Examination of the Urine and Urinary Diagnosis. A Clinical Guide for the Use of Practitioners and Students of Medicine and Surgery.
Authors: Jay Bergen Ogden
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Injuries in Traffic Accidents
Authors: G. Anthony Ryan
Journal: New England Journal of Medicine (1967)

THE first vehicle to move under its own power was a steam tractor built by Cugnot in France in 1769. A century later Siegfried Markus built the first car powered by an internal combustion engine, in Vienna, around 1870. However, Markus made only 4 cars, 1 of which survives to this day. It was Benz, in 1885, who made the first motorcar to be produced in appreciable numbers.2 Only eight years later the first recorded collision between motor vehicles occurred at Auteuil, France, in 1893, when Baron De Zuylen drove his horseless carriage into Count De Dion's motor brake. Apparently, . . .
Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial
Authors: Alfons JM van den Eertwegh, Jurjen Versluis, H Pieter van den Berg, Saskia JAM Santegoets, R Jeroen A van Moorselaar, Tim M van der Sluis, Helen E Gall, Thomas C Harding, Karin Jooss, Israel Lowy, Herbert M Pinedo, Rik J Scheper, Anita GM Stam, B Mary E von Blomberg, Tanja D de Gruijl, Kristen Hege, Natalie Sacks, Winald R Gerritsen
Journal: The Lancet Oncology (2012)
Surgery Plus Chemotherapy Compared With Surgery Alone for Localized Squamous Cell Carcinoma of the Thoracic Esophagus: A Japan Clinical Oncology Group Study—JCOG9204
Authors: Nobutoshi Ando, Toshifumi Iizuka, Hiroko Ide, Kaoru Ishida, Masayuki Shinoda, Tadashi Nishimaki, Wataru Takiyama, Hiroshi Watanabe, Kaichi Isono, Norio Aoyama, Hiroyasu Makuuchi, Otsuo Tanaka, Hideaki Yamana, Shunji Ikeuchi, Toshiyuki Kabuto, Kagami Nagai, Yutaka Shimada, Yoshihide Kinjo, Haruhiko Fukuda
Journal: Journal of Clinical Oncology (2003)

We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery.Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival.Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%, respectively (P =.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis.Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.
Comparison of the effects of gastric antisecretory agents in healthy volunteers and patients with duodenal ulcer.
Authors: C W Howden, D B Jones, D W Burget, R H Hunt
Journal: Gut (1986)

Thirty published studies of the clinical pharmacology of gastric antisecretory agents in normal volunteers and duodenal ulcer patients were reviewed. The aim was to investigate the relationship between antisecretory effect in the two populations. There was a significant correlation between effect in patients and normal subjects for suppression of 24 hour intragastric acidity (r = 0.732; p = 0.0068), nocturnal intragastric acidity (r = 0.861; p = 0.0033) and nocturnal acid output (r = 0.964; p = 0.0069). The regression lines for 24 hour and nocturnal acidity were very similar. The expected antisecretory effect of a particular dosage regimen in patients with duodenal ulcer can be predicted mathematically from data derived from studies in normal volunteers.
Co-Expression of IL-5 and Eotaxin-2 in Mice Creates a Novel and Eosinophil-dependent Pulmonary Model of Respiratory Inflammation Characteristic of Human Disease
Authors: S.I. Ochkur, T. Biechele, E. Jacobsen, B. McElhinney, C. Protheroe, R.S. Pero, M.T. Borchers, K.R. O'Neill, D.C. Colbert, M.P. McGarry, Y. Janssen-Heininger, C. Irvin, H.H. Shen, J.J. Lee, N.A. Lee
Journal: Journal of Allergy and Clinical Immunology (2007)
Exploring alternative narratives: the prioritisation of polio in northern Nigeria
Authors: James Smith
Journal: The Lancet Global Health (2014)

1present compelling evidence that lends support to the suggestion that the effi cacy of the oral poliovirus vaccine varies depending on its composition, thus reinforcing similar findings reported by Jenkins and colleagues in 2008. 2 However, the persistence of polio in the northern states of Nigeria cannot be adequately explained by the chemical properties of the vaccine and therefore warrants fur ther exploration. The global response to poliovirus has been shaped largely by the so-called smallpox paradigm: the assertion that disease eradication can be achieved with the successful application of efficacious medical technologies and targeted pharmacological interventions. 3
Lack of binding of bacterial lipopolysaccharide to mouse lung macrophages and restoration of binding by gamma interferon.
Authors: K S Akagawa, T Tokunaga
Journal: The Journal of Experimental Medicine (1985)

Although peritoneal resident macrophages (PRM) or peritoneal exudate macrophages (PEM) were activated by lipopolysaccharide (LPS) to kill tumor cells in vitro, lung macrophages (LM) obtained by mincing lung tissues or by harvesting bronchial lavage were not activated by LPS under any experimental conditions, i.e., different LPS concentrations, incubation times and cytotoxicity assay methods. The unresponsiveness of LM to LPS was seen in all of the mouse strains tested. Treatment of LM with indomethacin did not affect the unresponsiveness, although it greatly augmented the cytotoxicity of PRM stimulated with LPS. LM treated in vitro with crude lymphokines (LK) did not show cytotoxicity, but became sensitive to LPS and cytotoxic for tumor cells. LM treated first with crude LK and then with LPS were cytotoxic, but LM treated first with LPS and then with crude LK were not. The ability of crude LK to render LM responsive to LPS was neutralized by rabbit anti-mouse gamma interferon (IFN-gamma) antiserum but not by anti-mouse IFN-(alpha + beta) antiserum. LM treated with recombinant murine IFN-gamma became responsive to LPS and showed cytotoxicity. LM were resistant to direct toxicity of LPS under conditions in which significant populations of PRM and PEM died. However, LM became sensitive to direct toxicity of LPS by treatment with crude LK or recombinant murine IFN-gamma. Fluorescence microscopy showed that almost all PRM and PEM were stained with fluorescein isothiocyanate (FITC)-LPS, while less than 5% of the LM were stained. Instead, approximately 60% of the LM treated with the crude LK or recombinant IFN-gamma for 20 h were stained with FITC-LPS. Fluorescence-activated cell sorter (FACS) analysis confirmed this result. The staining of IFN-gamma treated LM with FITC-LPS was inhibited by polymyxin B or unlabeled LPS. These results suggest that the defective responsiveness of LM to LPS is due to the lack or very low expression of LPS-binding sites on the cell surface and that in vitro treatment with IFN-gamma brings about the expression of them and renders LM responsive to LPS.
Impact of Amoxicillin Prophylaxis on the Incidence, Nature, and Duration of Bacteremia in Children After Intubation and Dental Procedures
Authors: Peter B. Lockhart, Michael T. Brennan, M. Louise Kent, H. James Norton, David A. Weinrib
Journal: Circulation (2004)

Controversy exists about the impact of prophylactic antibiotics on bacteremia after invasive dental procedures. The purpose of this double-blind, randomized, placebo-controlled study was to determine the impact of amoxicillin prophylaxis on the incidence, nature, and duration of bacteremia from nasotracheal intubation and dental procedures in children.Children were randomly assigned before surgery to the American Heart Association (AHA)-recommended dose of amoxicillin or to a placebo. Aerobic and anaerobic blood cultures were drawn at 8 specific time points after intubation, dental restorative and cleaning procedures, and before, during, and after dental extraction(s), to include blood drawings up to 45 minutes after the last extraction. Aerobic and anaerobic blood culture results were used to determine the incidence, nature, and duration of bacteremia from these procedures. For the 100 children enrolled (mean age, 3.5 years), the overall incidence of positive blood cultures, defined as at least 1 positive culture of the 8, was significantly higher in the placebo (84%) than the amoxicillin group (33%) (P<0.0001). Bacteremia occurrence rates after intubation and after dental restorations and cleaning were 18% and 20% in the placebo group and 4% and 6% in the amoxicillin group (P=0.05 and P=0.07, respectively). At 1.5 minutes after the initiation of dental extractions, bacteremia occurred in 76% of the placebo group versus 15% of the amoxicillin group (P<0.001). The majority of the 152 positive cultures and of the 29 different bacteria identified were Gram-positive cocci. Bacteremia persisted longer in the placebo group.Bacteremia from these procedures occurs more often, from a wider variety of bacterial species, and for a longer duration after dental extractions than previously reported in any age group. Amoxicillin has a significant impact on the incidence, nature, and duration of bacteremia after nasal intubation, dental restorative and cleaning procedures, and dental extractions.