tbuckley/cabot-search huggingface dataset:
The natural history of hereditary pancreatitis: a national series
Authors: V Rebours, M-C Boutron-Ruault, M Schnee, C Ferec, C Le Marechal, O Hentic, F Maire, P Hammel, P Ruszniewski, P Levy
Journal: Gut (2008)

<h3>Background and aims:</h3> The prevalence and natural history of hereditary pancreatitis (HP) remain poorly documented. The aims of this study were to assess genetic, epidemiological, clinical and morphological characteristics of HP in an extensive national survey. <h3>Methods:</h3> A cohort comprising all HP patients was constituted by contacting all gastroenterologists and paediatricians (response rate 84%) and genetics laboratories (response rate 100%) in France (60 200 000 inhabitants). Inclusion criteria were the presence of mutation in the cationic trypsingen gene (PRSS1 gene), or chronic pancreatitis in at least two first-degree relatives, or three second-degree relatives, in the absence of precipitating factors for pancreatitis. <h3>Results:</h3> 78 families and 200 patients were included (181 alive, 6673 person-years, males 53%, alcoholism 5%, smoking 34%). The prevalence was 0.3/100 000 inhabitants. PRSS1 mutations were detected in 68% (R122H 78%, N29I 12%, others 10%). Penetrance was 93%. Median age at first symptom, diagnosis and date of last news, were 10 (range 1–73), 19 (1–80) and 30 (1–84) years, respectively. HP was responsible for pancreatic pain (83%), acute pancreatitis (69%), pseudocysts (23%), cholestasis (3%), pancreatic calcifications (61%), exocrine pancreatic insufficiency (34%, median age of occurrence 29 years), diabetes mellitus (26%, median age of occurrence 38 years) and pancreatic adenocarcinoma (5%, median age 55 years). No differences in clinical and morphological data according to genetic status were observed. 19 patients died, including 10 directly from HP (8 from pancreatic adenocarcinoma). <h3>Conclusion:</h3> The prevalence of HP in France is at least 0.3/100 000. PRSS1 gene mutations are found in 2/3 with a 93% penetrance. Mutation type is not correlated with clinical/morphological expression. Pancreatic adenocarcinoma is the cause of nearly half the deaths.
EXPERIMENTAL NEPHRITIS IN RATS INDUCED BY INJECTION OF ANTI-KIDNEY SERUM
Authors: Homer F. Swift, Joseph E. Smadel
Journal: The Journal of Experimental Medicine (1937)

A saline extract of perfused rat kidney administered intravenously to rats immediately before injecting an anti-rat-kidney serum, by the same route, prevents renal damage. A preliminary injection of physiological salt solution or of an extract of perfused rat liver has no preventive effect. These findings are a further indication that the nephrotoxic effect induced by anti-kidney serum is dependent upon a relatively organ specific antibody, nephrotoxin.
Rates of Vaccine Evolution Show Strong Effects of Latency: Implications for Varicella Zoster Virus Epidemiology
Authors: Lucy A. Weinert, Daniel P. Depledge, Samit Kundu, Anne A. Gershon, Richard A. Nichols, Francois Balloux, John J. Welch, Judith Breuer
Journal: Molecular Biology and Evolution (2015)

Varicella-zoster virus (VZV) causes chickenpox and shingles, and is found in human populations worldwide. The lack of temporal signal in the diversity of VZV makes substitution rate estimates unreliable, which is a barrier to understanding the context of its global spread. Here, we estimate rates of evolution by studying live attenuated vaccines, which evolved in 22 vaccinated patients for known periods of time, sometimes, but not always undergoing latency. We show that the attenuated virus evolves rapidly (∼10−6 substitutions/site/day), but that rates decrease dramatically when the virus undergoes latency. These data are best explained by a model in which viral populations evolve for around 13 days before becoming latent, but then undergo no replication during latency. This implies that rates of viral evolution will depend strongly on transmission patterns. Nevertheless, we show that implausibly long latency periods are required to date the most recent common ancestor of extant VZV to an "out-of-Africa" migration with humans, as has been previously suggested.
A review of human carcinogens—Part D: radiation
Authors: Fatiha El Ghissassi, Robert Baan, Kurt Straif, Yann Grosse, Béatrice Secretan, Véronique Bouvard, Lamia Benbrahim-Tallaa, Neela Guha, Crystal Freeman, Laurent Galichet, Vincent Cogliano
Journal: The Lancet Oncology (2009)
Glomerular Injury and Tubular Loss in Adriamycin Nephrosis
Authors: BASIT JAVAID, JEAN L. OLSON, TIMOTHY W. MEYER
Journal: Journal of the American Society of Nephrology (2001)

Glomerular injury manifested by sustained proteinuria usually leads to tubule injury and reduction of the GFR. The current study explored the link between these processes in rats with adriamycin nephrosis. One group of nephrotic rats received a vasopressin V2 receptor blocker (V2X) from 4 to 16 wk after injection of adriamycin, whereas a second group received no treatment (NoRx). V2 receptor blockade increased urine volume without affecting protein excretion. At 16 wk, both groups of nephrotic rats exhibited a marked reduction in GFR in comparison with normal controls (V2X, 0.22 +/- 0.19 ml/min; NoRx, 0.20 +/- 0.11 ml/min; control, 1.23 +/- 0.11 ml/min). Morphologic studies revealed that the majority of glomeruli in nephrotic rats were no longer connected to normal tubule segments (V2X, 81 +/- 21%; NoRx, 85 +/- 18%; control, 1 +/- 2%). Glomeruli without tubules were not, however, globally sclerosed. Disruption of the glomerular tubular junction was associated with the presence of amorphous material separating damaged tubule cells from the basement membrane. Serial sections revealed that this material spread from extensive areas of adhesion between the glomerular tuft and capsule to invest the tubular neck. Reduction of the GFR was strongly correlated with the fraction of glomeruli not connected to normal tubules (r(2) = 0.82; P < 0.0001). V2 receptor blockade did not preserve renal function or structure. These findings suggest that local extension of glomerular injury to destroy the tubule neck is an important cause of loss of renal function in adriamycin nephrosis.
FIRST-TRIMESTER FETAL DIAGNOSIS FOR HAEMOGLOBINOPATHIES: REPORT ON 200 CASES
Authors: J.M. Old, C. Heath, A. Fitches, S.L. Thein, D.J. Weatherall, R. Warren, C. Mckenzie, C.H. Rodeck, B. Modell, M. Petrou, R.H.T. Ward
Journal: The Lancet (1986)
Do Patients of Subspecialist Physicians Benefit from Written Asthma Action Plans?
Authors: Beverley J. Sheares, Robert B. Mellins, Emily Dimango, Denise Serebrisky, Yuan Zhang, Michael R. Bye, Mark E. Dovey, Sami Nachman, Vincent Hutchinson, David Evans
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Asthma clinical guidelines suggest written asthma action plans are essential for improving self-management and outcomes.To assess the efficacy of written instructions in the form of a written asthma action plan provided by subspecialist physicians as part of usual asthma care during office visits.A total of 407 children and adults with persistent asthma receiving first-time care in pulmonary and allergy practices at 4 urban medical centers were randomized to receive either written instructions (n = 204) or no written instructions other than prescriptions (n = 203) from physicians.Using written asthma action plan forms as a vehicle for providing self-management instructions did not have a significant effect on any of the primary outcomes: (1) asthma symptom frequency, (2) emergency visits, or (3) asthma quality of life from baseline to 12-month follow-up. Both groups showed similar and significant reductions in asthma symptom frequency (daytime symptoms [P < 0.0001], nocturnal symptoms [P < 0.0001], β-agonist use [P < 0.0001]). There was also a significant reduction in emergency visits for the intervention (P < 0.0001) and control (P < 0.0006) groups. There was significant improvement in asthma quality-of-life scores for adults (P < 0.0001) and pediatric caregivers (P < 0.0001).Our results suggest that using a written asthma action plan form as a vehicle for providing asthma management instructions to patients with persistent asthma who are receiving subspecialty care for the first time confers no added benefit beyond subspecialty-based medical care and education for asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00149461).
Outcomes Associated With Invasive and Noninvasive Ventilation Among Patients Hospitalized With Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Peter K. Lindenauer, Mihaela S. Stefan, Meng-Shiou Shieh, Penelope S. Pekow, Michael B. Rothberg, Nicholas S. Hill
Journal: JAMA Internal Medicine (2014)

Small clinical trials have shown that noninvasive ventilation (NIV) is efficacious in reducing the need for intubation and improving short-term survival among patients with severe exacerbations of chronic obstructive pulmonary disease (COPD). Little is known, however, about the effectiveness of NIV in routine clinical practice.To compare the outcomes of patients with COPD treated with NIV to those treated with invasive mechanical ventilation (IMV).This was a retrospective cohort study of 25 628 patients hospitalized for exacerbation of COPD who received mechanical ventilation on the first or second hospital day at 420 US hospitals participating in the Premier Inpatient Database.Initial ventilation strategy.In-hospital mortality, hospital-acquired pneumonia, hospital length of stay and cost, and 30-day readmission.In the study population, a total of 17 978 (70%) were initially treated with NIV on hospital day 1 or 2. When compared with those initially treated with IMV, NIV-treated patients were older, had less comorbidity, and were less likely to have concomitant pneumonia present on admission. In a propensity-adjusted analysis, NIV was associated with lower risk of mortality than IMV (odds ratio [OR] 0.54; [95% CI, 0.48-0.61]). Treatment with NIV was associated with lower risk of hospital-acquired pneumonia (OR, 0.53 [95% CI, 0.44-0.64]), lower costs (ratio, 0.68 [95% CI, 0.67-0.69]), and a shorter length of stay (ratio, 0.81 [95% CI, 0.79-0.82]), but no difference in 30-day all-cause readmission (OR, 1.04 [95% CI, 0.94-1.15]) or COPD-specific readmission (OR, 1.05 [95% CI, 0.91-1.22]). Propensity matching attenuated these associations. The benefits of NIV were similar in a sample restricted to patients younger than 85 years and were attenuated among patients with higher levels of comorbidity and concomitant pneumonia. Using the hospital as an instrumental variable, the strength of association between NIV and mortality was modestly attenuated (OR, 0.66 [95% CI, 0.47-0.91]). In sensitivity analyses, the benefit of NIV was robust in the face of a strong hypothetical unmeasured confounder.In a large retrospective cohort study, patients with COPD treated with NIV at the time of hospitalization had lower inpatient mortality, shorter length of stay, and lower costs compared with those treated with IMV.
Pathophysiology of Atrial Flutter
Authors: Emile G. Daoud, Fred Morady
Journal: Annual Review of Medicine (1998)

Atrial flutter is a macroreentrant tachyarrhythmia most often contained within the right atrium. Typical atrial flutter is defined on an electrocardiogram by the classic “sawtooth” pattern of flutter waves with negative polarity in leads II, III, and aVF. In contrast to atrial fibrillation, which is sustained by multiple reentrant wavelets defined by anatomic and/or functional barriers, typical atrial flutter is sustained by a single reentrant circuit defined by anatomical barriers. The isthmus of atrial tissue bordered by the inferior vena cava and the tricuspid annulus forms a critical zone of slow conduction in the reentry circuit of atrial flutter. The goal of radiofrequency catheter ablation is to create a line of conduction block across this isthmus. This line of block interrupts the flutter circuit and often provides long-term freedom from recurrence.
Dietary Fat Predicts Coronary Heart Disease Events in Subjects With Type 2 Diabetes
Authors: Minna Soinio, Markku Laakso, Seppo Lehto, Paula Hakala, Tapani Rönnemaa
Journal: Diabetes Care (2003)

OBJECTIVE—To investigate whether quantity or quality of dietary fat predicts coronary heart disease (CHD) events in middle-aged type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—The dietary habits of 366 type 2 diabetic men and 295 women, aged 45–64 years and free from CHD, were assessed with a 53-item food frequency questionnaire. They were followed up for 7 years. RESULTS—Men in the highest tertile of the polyunsaturated/saturated fat (P/S) ratio (&amp;gt;0.28) had a significantly lower risk for CHD death than men in the two lowest tertiles (5.0 vs. 14.2%, P = 0.009). The risk for all CHD events was 14.2 vs. 23.2%, respectively (P = 0.044). P/S ratio did not predict CHD events in women. In Cox multiple regression analyses taking into account other cardiovascular risk factors, the highest P/S ratio tertile was associated with the lowest rate of CHD death in men (P = 0.048). CONCLUSIONS—Low P/S ratio in men predicted future CHD events in type 2 diabetic subjects independently of conventional CHD risk factors.
Computer-aided selection of diagnostic tests in jaundiced patients.
Authors: M F Saint-Marc Girardin, M Le Minor, A Alperovitch, F Roudot-Thoraval, J M Metreau, D Dhumeaux
Journal: Gut (1985)

A model has been developed for ordering diagnostic tests in jaundiced patients. The system proceeds in two steps: (i) diagnostic hypotheses are calculated for each patient from the results of physical examination and routine biological investigations; (ii) given these hypotheses, the most efficient test (out of 22) for reaching the final diagnosis is selected using four criteria: diagnostic value, risk, financial cost, and time in obtaining the result. This model was tested in 62 patients. In 43 of them (69%), the selected test was sufficient for reaching a diagnostic accuracy of 100%. In this group of patients, a mean of 3.7 (range 1-6) tests per patient was ordered by physicians. In the 19 remaining patients, the selected test was not sufficient for the final diagnosis, thus requiring a multiple choice process. It is suggested that such a system could help physicians to improve the care of patients by more efficient ordering of diagnostic tests.
Genomic imprinting in diabetes
Authors: Braxton D Mitchell, Toni I Pollin
Journal: Genome Medicine (2010)

Genomic imprinting refers to a class of transmissible genetic effects in which the expression of the phenotype in the offspring depends on the parental origin of the transmitted allele. The DNA from one parent may be epigenetically modified so that only a single allele of the imprinted gene is expressed in the offspring. Although imprinting has an important role in the regulation of growth and development through its role in regulating gene expression, its contribution to susceptibility to common complex disorders is not well understood. We summarize current views on the role of imprinting in diabetes and in particular chromosome 6q24-related transient neonatal diabetes mellitus, the best known example of an imprinted genetic disorder that leads to diabetes.
Die Resozialisierung yon sexuell abnormen Patienten durch kombinierte Antiandrogen-Applikation und Psychotherapie
Authors: H.J. von Schumann
Journal: Psychotherapy and Psychosomatics (1972)

The sexual dynamics of the personality with anomalous sexual attitudes and perversions are often so powerful that psychotherapy is without effect. In order to render such patients accessible to psychotherapy, I have used the antiandrogen cyproterone acetate (Schering). By means of this combined therapy, sex deviants such as compulsive masturbators and sadists, and delinquents such as exhibitionists, pederasts, rapists and kleptomaniacs can be rehabilitated socially and professionally. In many cases, it was necessary to treat the wives also, as they had been frustrating their husbands sexually and thus driving them to deviant or delinquent behaviour.
Abstract 562: Impact of ERα expression status and ESR1 genetic variation on progression in tamoxifen-treated breast cancer patients
Authors: Nataliya Babyshkina, Sergey Vtorushin, Stanislav Patalyak, Tatyana Dronova, Elena Slonimskaya, Nadejda Cherdyntseva
Journal: Cancer Research (2014)

Abstract Background. Resistance to tamoxifen remains a major clinical challenge in the treatment of breast cancer. The aim of this study was to evaluate the influence of the intensity and the pattern of estrogen receptor α (ERα) expression and common single nucleotide polymorphisms (SNP) in the estrogen receptor 1 gene (ESR1, rs2228480:2014G&amp;gt;A; rs2077647:+30T&amp;gt;C) on disease progression in breast cancer patients who received adjuvant tamoxifen. Material and methods. Formalin-fixed paraffin-embedded tumor tissue samples were retrospectively collected from 61 patients, who had distant metastasis versus distant metastasis-free breast cancers (n = 37 versus n = 24, respectively, with a 9-year follow-up). Protein expression of ER, PR and HER2 were assessed by immunohistochemistry. Real-time polymerase chain reaction analysis was used to determine the ESR1 SNPs. Results. We found that the heterogeneous distribution of ERα was statistically significant related with a low expression level and intensity of ERα in tumor tissue samples (p=0.002 and p=0.0002, respectively). In addition, the level and intensity of ERα expression was lower in patients with distant metastasis compared to distant metastasis-free cases, but these differences were not significant (P&amp;gt;0.05). Nonetheless, the ESR1 2014A allele was associated with a heterogeneous distribution of ERα expression (p=0.02). We showed the higher risk of distant metastasis development for the patients carrying the ESR1 2014A mutant allele compared with women with ESR1 2014G variant (p=0.04). Conclusion. These data suggest that the expression level and intensity of ERα with ESR1 2014G&amp;gt;A genetic variation could be a useful molecular markers for predicting tamoxifen treatment prognosis in breast cancer patients. Citation Format: Nataliya Babyshkina, Sergey Vtorushin, Stanislav Patalyak, Tatyana Dronova, Elena Slonimskaya, Nadejda Cherdyntseva. Impact of ERα expression status and ESR1 genetic variation on progression in tamoxifen-treated breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 562. doi:10.1158/1538-7445.AM2014-562
Enteral supplementation of alanyl–glutamine attenuates the up-regulation of beta-defensin-2 protein in lung injury induced by intestinal ischemia reperfusion in rats
Authors: Yun Li, Xiao-Bin Wu, Jia-Gen Li, Yi-Jia Lin, Hong-Lei Chen, Hu Song, Zhong-Hui Liu, Jun-Sheng Peng
Journal: International Journal of Surgery (2014)

Beta-defensin-2 (BD-2), an endogenous antimicrobial peptide, plays a key role in immune response against microbial invasion. This study aimed to observe the effect of Alanyl-Glutamine (Ala-Gln) on BD-2 protein expression in pulmonary tissues after intestinal ischemia reperfusion (IIR) in rats and to investigate its correlations to pulmonary inflammatory and oxidative injury.Rats in IIR and the two treatment groups were subjected to intestine ischemia for 60 min and those in the treatment groups were administered orally with Ala-Gln or alanine (Ala) respectively. Lung tissues were harvested to detect the BD-2 protein expression. Concentrations of Tumor necrosis factor (TNF)-α and malondialdehyde (MDA) as well as superoxide dismutase (SOD) activity in lung tissues were determined simultaneously.Ala-Gln attenuated the up-regulation of BD-2 expression (p < 0.05) and TNF-α (p < 0.05), MDA (p < 0.05) levels, as well as the reduction of SOD activity (p < 0.05) in lung tissues after IIR. But Ala did not exert significant effects. BD-2 protein in lung tissues was positively correlated to local TNF-α level (p < 0.01) and MDA concentration (p < 0.01) with statistical significance.Ala-Gln can relieve the IIR-induced up-regulation of BD-2 protein expression in the lung of rats, which involves anti-inflammation and anti-oxidation mechanisms.
Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study
Authors: Thomas Voit, Haluk Topaloglu, Volker Straub, Francesco Muntoni, Nicolas Deconinck, Giles Campion, Sjef J De Kimpe, Michelle Eagle, Michela Guglieri, Steve Hood, Lia Liefaard, Afrodite Lourbakos, Allison Morgan, Joanna Nakielny, Naashika Quarcoo, Valeria Ricotti, Katie Rolfe, Laurent Servais, Claire Wardell, Rosamund Wilson, Padraig Wright, John E Kraus
Journal: The Lancet Neurology (2014)
Alternative mRNA Splicing of Liver Intestine-Cadherin in Hepatocellular Carcinoma
Authors: Xiao Qi Wang, John M. Luk, Pauline P. Leung, Bonnie W. Wong, Eric J. Stanbridge, Sheung Tat Fan
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To identify alternative splicing of the liver intestine-cadherin (LI-cadherin) gene in hepatocellular carcinoma (HCC) and correlate its aberrant expression with clinical outcomes. Experimental Design: Reverse transcription-PCR (RT-PCR) and quantitative real-time RT-PCR were used to examine alternative mRNA splicing and mRNA level of LI-cadherin in 50 paired tumor-peritumor tissues of 50 HCC and 8 normal liver specimens. The minigene exon-trapping strategy was employed to investigate the splicing mechanism introduced by nucleotide polymorphisms. Association of LI-cadherin splicing with tumor venous infiltration, first-year tumor recurrence, and overall survival after partial hepatectomy were determined. Results: Alternative mRNA splicing of LI-cadherin was identified in half of the HCC specimens. Sequencing analysis indicated the loss of exon 7 in the spliced LI-cadherin gene. LI-cadherin mRNA was up-regulated from 2.58-fold to 800-fold in over 80% of HCC samples when compared with normal liver by quantitative PCR. Furthermore, nucleotide polymorphisms were identified in putative branch point at IVS6 + 35 (intron 6) as well as in coding sequence 651 (exon 6) in HCC tissues, which may affect alternative mRNA splicing. Clinically, those patients who harbored the alternative splicing of LI-cadherin were strongly associated with shorter overall survival time (P &amp;lt; 0.01) as well as higher incidences of tumor recurrences and venous infiltration (both P &amp;lt; 0.05) after hepatectomy. Conclusions: Over-expression of LI-cadherin was frequently detected in liver cancer patients. Aberrant alternative splicing of LI-cadherin was detected in 50% of HCC specimens and its clinical significance hinted at early tumor recurrence and poor overall survival of HCC patients.
Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation
Authors: Dao-Pei Lu, Lujia Dong, Tong Wu, Xiao-Jun Huang, Mei-Jie Zhang, Wei Han, Huan Chen, Dai-Hong Liu, Zhi-Yong Gao, Yu-Hong Chen, Lan-Ping Xu, Yao-Chen Zhang, Han-Yun Ren, Dan Li, Kai-Yan Liu
Journal: Blood (2005)