tbuckley/cabot-search huggingface dataset:
Nucleotide Excision Repair Gene Polymorphisms and Recurrence after Treatment for Superficial Bladder Cancer
Authors: Jian Gu, Hua Zhao, Colin P. Dinney, Yong Zhu, Dan Leibovici, Carlos E. Bermejo, H. Barton Grossman, Xifeng Wu
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Interindividual differences in DNA repair capacity not only modify individual susceptibility to carcinogenesis, but also affect individual response to cancer treatment. Nucleotide excision repair (NER) is one of the major DNA repair pathways in mammalian cells involved in the removal of a wide variety of DNA lesions. Polymorphisms in NER genes may influence DNA repair capacity and affect clinical outcome of bladder cancer treatment. Experimental Design: To test the influence of NER gene polymorphisms on superficial bladder cancer outcome (recurrence and progression), we conducted a follow-up study of 288 patients with superficial bladder cancer. Median follow-up among patients who were recurrence-free at the end of observation was 21.7 months from diagnosis. The specific polymorphic loci examined include XPA [A/G at 5′ untranslated region (UTR)], XPC (poly AT, Ala499Val, Lys939Gln), XPD (Asp312Asn, Lys751Gln), XPG (His1104Asp), ERCC 1 (G/T at 3′ UTR), and ERCC6 (Met1097Val, Arg1230Pro). Results: The ERCC6 (Met1097Val) polymorphism had a significant impact on recurrence: carriers of at least one variant allele (Val) had a significantly higher recurrence risk than carriers of the wild-type allele (Met/Met; hazard ratio, 1.54; 95% confidence interval, 1.02-2.33). There were no overall statistically significant differences in the distributions of the other polymorphisms between patients with and without recurrence. However, when we combined these variant genotypes, there was a significant trend for an increased recurrence risk with an increasing number of putative high-risk alleles. Using individuals with five or fewer putative high-risk alleles as the reference group, individuals with six to seven risk alleles and individuals with eight or more risk alleles had higher recurrence risks, with hazard ratios of 0.92 (0.54-1.57) and 2.53 (1.48-4.30), respectively (P for trend &amp;lt; 0.001). There was also a significant trend for shorter recurrence-free survival time with increasing number of variant alleles (log rank test, P = 0.0007). When we stratified the patients according to intravesical Bacillus Calmette-Guerin treatment, we found a significant trend for shorter recurrence-free survival time in patients with variant alleles of XPA or ERCC6 polymorphisms who received Bacillus Calmette-Guerin treatment (log rank test, P = 0.078 and 0.022, respectively). There were no significant individual or joint associations between these polymorphisms and progression. Conclusions: These data suggest that interindividual differences in DNA repair capacity may have an important impact on superficial bladder cancer recurrence. A pathway-based approach is preferred to study the effects of individual polymorphism on clinical outcomes.
Early emergency care study: the potential and benefits of advanced prehospital care.
Authors: I W Anderson, R J Black, I M Ledingham, K Little, C E Robertson, J D Urquhart
Journal: BMJ (1987)

Of 26358 patients taken by ambulance to the accident and emergency departments of two large hospitals, 1185 were admitted to resuscitation areas. The scope for ambulance staff to employ a range of advanced techniques at the scene of incidents was assessed by using information relating to the condition of patients when they were picked up by the ambulance and on admission, time in transit, details from hospital records, and outcome at three months. For non-survivors further assessment was made of the benefit, in terms of survival, which might have accrued had advanced techniques been used. The results of the assessment of benefit were compared with estimates of benefit from other studies. In cases of cardiopulmonary arrest the potential to save lives was less optimistic than earlier estimates, and in cases of trauma the potential to save lives was negligible.
Australia to mandate plain packs for cigarettes as part of new tobacco control offensive
Authors: M. Sweet
Journal: BMJ (2010)

Australia plans to become the first country in the world to mandate plain packaging of cigarettes as part of a raft of new tobacco control measures.

The Australian government also announced today a 25% hike in tobacco excise, which it predicts will cut the country’s total tobacco consumption by around 6%.

The move to plain packaging, to be introduced by mid 2012, will restrict or ban the use of tobacco industry logos, brand imagery, colours, and promotional text other than brand and product names in a standard colour, position, font style, and size.

The government plans to develop and test package design to make cigarettes less appealing, particularly to young people. It will also crack down …
Validation of the 6 min walk test according to the OMERACT filter: a systematic literature review by the EPOSS-OMERACT group
Authors: J. Avouac, O. Kowal-Bielecka, D. Pittrow, D. Huscher, F. Behrens, C. P. Denton, I. Foeldvari, M. Humbert, M. Matucci-Cerinic, P. Nash, C. F. Opitz, L. J. Rubin, J. R. Seibold, O. Distler, D. E. Furst
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To assess the validity of the 6 min walk test (6MWT) in pulmonary arterial hypertension secondary to systemic sclerosis (PAH-SSc) according to the OMERACT filter. <h3>Methods</h3> A systematic literature search was conducted from 1966 through June 2009. The assessment of validation of the 6MWT was based on the OMERACT filter criteria with the domains 'truth', 'discrimination' and 'feasibility'. <h3>Results</h3> From the 57 articles identified, 9 (16%) were analysed. The 6MWT had face validity as it has been accepted by the registration agencies as a surrogate of PAH-SSc. It was sensitive to change in response to therapy, with effect sizes ranging from 0.30 to 1.37 with a parallel variation of haemodynamic parameters measured by right heart catheterisation. Feasibility was also validated. Content validity was not confirmed as this test was not specific for PAH-SSc. There was some evidence that 6MWT might meet criterion/construct validity, reproducibility and sensitivity to change over time, but insufficient data were provided to fully validate these components. <h3>Conclusions</h3> Current evidence suggests partial validation of the 6MWT in PAH-SSc according to the OMERACT filter. Further dedicated studies are needed to validate completely the 6MWT in PAH-SSc, taking into account the comorbidities interfering with the 6MWT.
Experimental angina treatment rejected by the FDA
Authors: D. Josefson
Journal: BMJ (1997)

An advisory committee of the Food and Drug Administration has recommended rejecting transmyocardial revascularisation as a treatment for angina. Currently an experimental treatment of last resort, the two hour procedure entails drilling small holes by laser into the heart in the hope that revascularisation of the myocardium will occur.

PLC systems, manufacturer of the laser used in transmyocardial revascularisation, had applied for the Food and Drug Administration's approval of the device and the procedure itself. Dr Mahmood Mirhoseini of St Luke's Medical Center in Milwaukee, Wisconsin, pioneered the treatment in an effort to provide an alternative method of myocardial perfusion in patients with ischaemic heart and coronary artery disease. It was developed after several investigators showed that reptiles and some fish achieve myocardial perfusion through direct diffusion of oxygen rich blood from the ventricular cavity into the surrounding cardiac muscle. Researchers believed that by surgically …
Renal nerves modulate renin gene expression in the developing rat kidney with ureteral obstruction.
Authors: S S el-Dahr, R A Gomez, M S Gray, M J Peach, R M Carey, R L Chevalier
Journal: Journal of Clinical Investigation (1991)

Chronic unilateral ureteral obstruction (UUO) in newborn rats activates renin gene expression in the obstructed kidney, and increases renin distribution along afferent glomerular arterioles in both kidneys. To investigate the role of the renal nerves in this response, 2-d-old Sprague-Dawley rats were subjected to UUO or sham operation. Chemical sympathectomy was performed by injection of guanethidine, whereas, control groups received saline vehicle. At 4-5 wk, renal renin distribution was determined by immunocytochemistry, and renin mRNA levels were determined by Northern blot hybridization. Compared to the saline-treated rats with UUO, renin remained localized to the juxtaglomerular region in both kidneys of rats with UUO receiving guanethidine (P less than 0.05). Moreover, renin mRNA levels were eightfold lower in obstructed kidneys of rats receiving guanethidine than in those receiving saline. Additional groups of rats with UUO were subjected to unilateral mechanical renal denervation: renin gene expression in the obstructed kidney was suppressed by ipsilateral but not by contralateral renal denervation. These findings indicate that either chemical or mechanical denervation suppressed the increase in renin gene expression of the neonatal kidney with ipsilateral UUO. We conclude that the renal sympathetic nerves modulate renin gene expression in the developing kidney with chronic UUO.
In situ quantitative monitoring of polyplexes and polyplex micelles in the blood circulation using intravital real-time confocal laser scanning microscopy
Authors: Takahiro Nomoto, Yu Matsumoto, Kanjiro Miyata, Makoto Oba, Shigeto Fukushima, Nobuhiro Nishiyama, Tatsuya Yamasoba, Kazunori Kataoka
Journal: Journal of Controlled Release (2011)
Commentary: Understanding social network analysis
Authors: P. Sainsbury
Journal: BMJ (2008)

In the linked study (doi:10.1136/bmj.a2338), Fowler and Christakis investigated the new and intriguing hypothesis that people’s happiness is influenced by, among other things, the happiness of their acquaintances, particularly first degree relatives, close friends, neighbours, and coworkers.1 The authors cleverly use the Framingham heart study’s existing database that includes, fortuitously rather than by design, information that can be used for social network analysis. Their results broadly confirm this hypothesis, but many readers will be unfamiliar with social network analysis, confused by the analytical techniques, and unsure about the validity of the findings.

Humans are unavoidably social beings. Consequently, not only does society exist, but its existence is inevitable, and each person is influenced in many ways by society at large and individuals and groups within it. It follows that to understand the attributes of individuals (for instance their …
P2-09-08: FDG-PET in the Staging of the Axilla in Women with Breast Cancer Treated with Primary Chemotherapy.
Authors: Romera J Lao, Hernandez T Puértolas, Alejandro M Alvarez, Molias A Godoy, Garcia A Hernandez, Bocos E Millastre, Mur C Garcia, Laguarda MA Ubieto, Cortes A Artal, Torres A Anton
Journal: Cancer Research (2011)

Abstract Background FDG-PET has proven to be useful during the initial staging of several tumor types. The aim of the present study was to assess the accuracy of this test in the assessment of initial axillary status in patients referred to treatment with induction chemotherapy. Material and Methods: Women with stage II-IIIA (tumors measuring ≥3cm or positive-staged axillary involvement) to be treated with neoadjuvant Docetaxel-Doxorubicin-Cyclophosphamide (TAC scheme) were included. In every patient a physical exam, MRI, ultrasound-guided FNAB and FDG-PET were performed prior starting chemotherapy. The criteria to consider the axilla to be initially positive were positive surgical staging or type-D pathological response (Miller-Payne) in the axilla. The ability of FDG-PET to predict pathological response in patients with breast cancer was assessed and compared with other routine procedures. Results: 42 patients (p) were included. Median age was 45 years (30-66). 11p (26.2%) were triple-negative. 2p (4.8%) were Her-2 +. By clinical stage, 13p (30.9%) were IIA, 17p (40.4%) IIB and 12p (28.2%) IIIA. 41p (97.6%) underwent surgery after induction chemotherapy. According to surgical staging 31p (75.6%) were deemed to be N+ from the diagnosis (19p with pathologic N1-3a and 12p with type-D nodal response). PET scan positively detected deposits in the axilla in 26p (83.9%) of those patients compared to 22p (70.9%) with ultrasound-FNAB, 19p (61.3%) physical exam and 14p (45.2%) MRI. Conclusions: In this study FDG-PET could predict axillary involvement more precisely than other routine staging procedures in these patients submitted to be treated with induction chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-08.
Pathology of Sickle Cell Disease
Authors: L. W. Diggs
Journal: JAMA (1971)

The book consists of an assembly of abstracts of 1,033 publications related to sickle cell diseases, through 1965, with a few abstracts for the years 1966-1969. The 19 chapters deal mainly with the anatomical changes in various organs as observed by others and supplemented by the author's observations as a pathologist. Other topics include historical background, the chemistry of the hemoglobin molecule, pathophysiology, incidence, genetics, clinical features, complications, and therapy. In general the contributions of various investigators are given in time sequence. The essential facts are presented in a scholarly and easily read manner. The printing is excellent, the typographical and factual errors few and the black-and-white illustrations sharp and well reproduced. The author does not state the incidence of the anatomical lesions in different organs at various ages. The observations of others are accurately and fairly stated. There is little critical analysis by the author. The terms "thrombi" and
Entry into occupational medicine
Authors: B. Lee
Journal: BMJ (1978)

Omeprazole plus amoxicillin cures Helicobacter pylori infection. The hypothesis was tested that low acidity is a predictor of outcome. Fifty patients with relapsing or complicated, or both H pylori positive duodenal (n = 25) or gastric ulcer (n = 25) were randomly treated with either omeprazole 20 mg twice daily plus amoxicillin 1 g twice daily or with omeprazole 40 mg twice daily plus amoxicillin 1 g twice daily over two weeks. After one week of combined treatment, a 24 hour gastric pH measurement was performed in all patients. H pylori cure rate was 67%. Patients who later turned out to be cured had higher pH values during night time and after meals (p &lt; 0.05). In an explorative analysis drug compliance, smoking, location of the ulcer (duodenum versus stomach), age, and grade of body gastritis were additional predictors of the outcome. Smoking (p = 0.006), compliance (p = 0.037), duodenal ulcer disease (p = 0.065), and young age (p = 0.021) were related to high acidity. In conclusion, the success of eradication treatment with omeprazole and amoxicillin in ulcer patients infected with H pylori depends on intragastric pH. Drug compliance, smoking habits, location of ulcer, age, and activity of body gastritis are other predictors and in part related to intragastric acidity.
Primary care trusts are warned against making "unthinking cuts" in face of credit crunch
Authors: C. White
Journal: BMJ (2009)

<i>Abstract</i>. There is convincing evidence for a specific BP-independent effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular disease is not consistently halted by these agents, there is a need to explore potential renoprotective effects of other drugs. Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner. A randomized, crossover design was used to assess the human relevance of the experimental data in 15 normotensive, nonsmoking type 1 diabetic mellitus patients with good glycemic control (age, 37.3 ± 6.6 yr; 9 men/6 women; duration of diabetes, 23.6 ± 5.1 yr) with baseline urinary albumin excretion rates (AER) &gt;20 μg/min in the run-in phase. AER was assessed in overnight timed urine collections. The patients were assigned to a 3-wk placebo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in random order. This dose causes modest BP lowering in hypertensive individuals but does not affect BP in normotensive individuals. There was no significant effect on ambulatory BP (mean arterial pressure, 91.8 ± 7.1 mmHg in the third week of placebo and 91.1 ± 8.7 mmHg on moxonidine). There was a significant (<i>P</i> &lt; 0.006) difference of the treatment effects between placebo and moxonidine, respectively, on AER; median AER at the end of the placebo period was 39.8 μg/min (range, 15.9 to 117 μg/min) <i>versus</i> 29.0 (range, 9.03 to 85.8 μg/min) at the end of the moxonidine period. The data document an antialbuminuric effect of nonhypotensive doses of moxonidine. Diminished sympathetic traffic to the kidney is the most plausible explanation for the finding.
Sex Differences in Attainment of Independent Funding by Career Development Awardees
Authors: Reshma Jagsi, Amy R Motomura, Kent A Griffith, Soumya Rangarajan, Peter A Ubel
Journal: Annals of Internal Medicine (2009)

Background: Concerns have been raised about the career pipeline in academic medicine, including whether women with a demonstrated commitment to research succeed at the same rate as male colleagues. Objective: To determine the subsequent academic success of recipients of National Institutes of Health (NIH) career development awards. Setting: United States. Participants: 2784 of 2799 (99.5%) recipients of K08 and K23 awards for whom sex could be ascertained from the NIH Computer Retrieval of Information on Scientific Projects database and other publicly available sources. Measurements: Actuarial rates at which recipients of K08 and K23 awards from 1997 to 2003 went on to receive R01 awards. Sex-specific rates of R01 award attainment were calculated by using the Kaplan–Meier method, and sex differences were assessed by using a Cox proportional hazards model. Results: Overall, 31.4% of the 1919 K08 awardees and 43.7% of the 865 K23 awardees were female (P < 0.001). Women were less likely than men to receive an R01 award (P < 0.001). The actuarial rate of R01 award attainment at 5 years was 22.7% overall, 18.8% among women, and 24.8% among men. At 10 years, the rate was 42.5% overall, 36.2% among women, and 45.6% among men. Sex persisted as an independent significant predictor of R01 award attainment (hazard ratio, 0.79 [95% CI, 0.68 to 0.92]; P = 0.002) in multivariate analysis controlling for K award type, year of award, funding institute, institution, and specialty. Limitation: Whether the lower rate of R01 award achievement among women is due to lower rates of application or lower rates of success in application could not be determined. Conclusion: Only a minority of K awardees studied achieved R01 award funding during the period assessed, and a significant sex disparity was evident.
Immunologic response to aerosols of affinity-purified antigen in hypersensitivity pneumonitis
Authors: W.E. Stricker, J.E. Layton, H.A. Homburger, J.A. Katzmann, M.C. Swanson, R.E. Hyatt, C.E. Reed
Journal: Journal of Allergy and Clinical Immunology (1986)
Abortions in America: The Effects of Restrictive Funding
Authors: Lawrence R. Berger
Journal: New England Journal of Medicine (1978)

Following legalization of abortion in the U.S., dramatic declines were noted in infant mortality, deaths and complications from illegal abortions, rates of illegitimate births, and numbers of newborns abandoned for adoption. It is believed that improved quality of and access to medical care and more widespread use of family planning services also contributed to these declines. Restrictions on government funding for abortions may reverse these gains; that will depend on the alternatives women with unwanted pregnancies choose. It is predicted that a restriction of public money for legal abortion will cause increased maternal mortality, lead to a rise in the birth of defective fetuses, and cause teenage childbearing to rise. Adverse physical and psychological sequelae to abortion have not been found to occur. It is urged that the medical and social barriers for poor women to obtain abortions not be rebuilt.
TCT-519 Comparison of Wound Healing in Critical Limb Ischemia according to Wound Types with and without Successful Revascularization
Authors: Norihiro Kobayashi, Toshiya Muramatsu, Reiko Tsukahara, Yoshiaki Ito, Hiroshi Ishimori, Keisuke Hirano, Masatsugu Nakano
Journal: Journal of the American College of Cardiology (2013)
FURTHER STUDIES ON T. LEWISI INFECTION IN ALBINO RATS
Authors: David Perla, J. Marmorston-Gottesman
Journal: The Journal of Experimental Medicine (1930)

T. lewisi infection in normal adult 3 month old albino rats raised from a single stock and maintained under identical conditions was studied. Daily quantitative estimates of the trypanosomes in the circulating blood were made and the course of the infection was studied. Bilateral suprarenalectomy in rats lowers the resistance to a subsequent infection with T. lewisi. About 70 per cent of these rats die in an average period of 5.8 days after injection. The multiplication of the parasites, in the circulating stream, however, is not more considerable in the suprarenalectomized than in the previously normal rats, nor is the duration of the disease in the surviving rats any longer than in the normal group. The removal of the suprarenal glands does not alter the immune reaction to the parasite, but lowers the natural resistance of the animal to the toxic effects of the protozoan infection. Bilateral suprarenalectomy does not lessen the immunity of rats recovered from T. lewisi infection to subsequent infection. Unilateral nephrectomy does not influence the course of a subsequent infection with T. lewisi infection. The mortality of splenectomized rats from Bartonella muris anemia increases from 30 to 100 per cent following the injection of T. lewisi at the height of the anemia 7 days after splenectomy. T. lewisi infection 48 days after splenectomy that is to say at a time when the Bartonella anemia is no longer present produces a more severe infection than in normal rats. The number of trypanosomes at the height of infection averages 3 times the ordinary and the infection endures twice as long. Both the immune substance that inhibits the reproduction of the parasite and the lytic factor are markedly depressed. Splenic autotransplantation performed 4 weeks prior to splenectomy raises the resistance of rats to a subsequent T. lewisi infection. Thymectomy in 6 week old rats diminishes the severity of a subsequent trypanosome infection and shortens its course. Both the formation of the immune substance which inhibits reproduction of the trypanosomes and formation of trypanolytic antibodies are stimulated by this procedure. In the adult rat thymectomy shortens the course of the infection but the severity is only slightly diminished. Bilateral gonadectomy in the adult increases the severity of the infection. The number of trypanosomes at the height of the infection is almost three times the normal. However, the duration of the infection is the same as in the normal rats. The reproduction-inhibiting factor is depressed by bilateral gonadectomy but not the trypanocidal factor. Unilateral gonadectomy does not influence the infection.