tbuckley/cabot-search huggingface dataset:
Cytodiagnosis in the management of extrahepatic biliary stricture.
Authors: L A Desa, A B Akosa, S Lazzara, P Domizio, T Krausz, I S Benjamin
Journal: Gut (1991)

A total of 117 patients presenting with extrahepatic biliary strictures between 1981 and 1989 had 206 cytological examinations of the bile duct or bile (153 non-operative, 53 intraoperative) to establish the presence of malignancy. A final diagnosis of cholangiocarcinoma was made in 88 patients, with 29 patients having benign biliary strictures. The cytological techniques used were fine needle aspiration (n = 102) or brushing (n = 24) of the bile duct, or exfoliative cytology of bile (n = 80). Forty one patients with malignancy had two or more examinations with differing results between samples in 20 cases. The overall sensitivity was 72%. There was only one false positive result, giving a patient predictive value of positive cytology of 98%. Intraoperative cytology was more sensitive than non-operative examination (80% v 42%). Overall, the sensitivity of fine needle aspiration (67%) was greater than that of brush cytology (40%) or exfoliative cytology (30%). No complications were encountered. Cytodiagnosis of extrahepatic biliary strictures is a safe procedure which is not technically demanding, and as it has a high sensitivity and predictive value for positive cytology, cytological confirmation of malignancy should be sought in all clinically and radiologically suspicious cases.
Starvation and Semistarvation Diets in the Management of Obesity
Authors: Janis S. Fisler, Ernst J. Drenick
Journal: Annual Review of Nutrition (1987)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
155 INFLUENCE OF ESTROGEN ON THE EARLY RECOVERY OF HEPATOBILIARY SECRETORY FUNCTION AFTER ISCHEMIA/REPERFUSION INJURY IN RATS
Authors: A.H. de Vries, F.A.M. Ponds, R.T.A. Padbury, R.J. Porte, V.B. Nieuwenhuijs, G.J. Barritt
Journal: Journal of Hepatology (2009)
Multiple Phenotypes in Phosphoglucomutase 1 Deficiency
Authors: Laura C. Tegtmeyer, Stephan Rust, Monique van Scherpenzeel, Bobby G. Ng, Marie-Estelle Losfeld, Sharita Timal, Kimiyo Raymond, Ping He, Mie Ichikawa, Joris Veltman, Karin Huijben, Yoon S. Shin, Vandana Sharma, Maciej Adamowicz, Martin Lammens, Janine Reunert, Anika Witten, Esther Schrapers, Gert Matthijs, Jaak Jaeken, Daisy Rymen, Tanya Stojkovic, Pascal Laforêt, François Petit, Olivier Aumaître, Elzbieta Czarnowska, Monique Piraud, Teodor Podskarbi, Charles A. Stanley, Reuben Matalon, Patricie Burda, Soraya Seyyedi, Volker Debus, Piotr Socha, Jolanta Sykut-Cegielska, Francjan van Spronsen, Linda de Meirleir, Pietro Vajro, Terry DeClue, Can Ficicioglu, Yoshinao Wada, Ron A. Wevers, Dieter Vanderschaeghe, Nico Callewaert, Ralph Fingerhut, Emile van Schaftingen, Hudson H. Freeze, Eva Morava, Dirk J. Lefeber, Thorsten Marquardt
Journal: New England Journal of Medicine (2014)

Congenital disorders of glycosylation are genetic syndromes that result in impaired glycoprotein production. We evaluated patients who had a novel recessive disorder of glycosylation, with a range of clinical manifestations that included hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest.Homozygosity mapping followed by whole-exome sequencing was used to identify a mutation in the gene for phosphoglucomutase 1 (PGM1) in two siblings. Sequencing identified additional mutations in 15 other families. Phosphoglucomutase 1 enzyme activity was assayed on cell extracts. Analyses of glycosylation efficiency and quantitative studies of sugar metabolites were performed. Galactose supplementation in fibroblast cultures and dietary supplementation in the patients were studied to determine the effect on glycosylation.Phosphoglucomutase 1 enzyme activity was markedly diminished in all patients. Mass spectrometry of transferrin showed a loss of complete N-glycans and the presence of truncated glycans lacking galactose. Fibroblasts supplemented with galactose showed restoration of protein glycosylation and no evidence of glycogen accumulation. Dietary supplementation with galactose in six patients resulted in changes suggestive of clinical improvement. A new screening test showed good discrimination between patients and controls.Phosphoglucomutase 1 deficiency, previously identified as a glycogenosis, is also a congenital disorder of glycosylation. Supplementation with galactose leads to biochemical improvement in indexes of glycosylation in cells and patients, and supplementation with complex carbohydrates stabilizes blood glucose. A new screening test has been developed but has not yet been validated. (Funded by the Netherlands Organization for Scientific Research and others.).
BMI and Diabetes Risk in Singaporean Chinese
Authors: Andrew O. Odegaard, Woon-Puay Koh, Gabrielle Vazquez, Kazuko Arakawa, Hin-Peng Lee, Mimi C. Yu, Mark A. Pereira
Journal: Diabetes Care (2009)

OBJECTIVE Increased BMI is a robust risk factor for type 2 diabetes. Paradoxically, South Asians have relatively low BMIs despite their high prevalence of type 2 diabetes. We examined the association between BMI and incident type 2 diabetes because detailed prospective cohort data on this topic in Asians are scarce. RESEARCH DESIGN AND METHODS This study was a prospective analysis of 37,091 men and women aged 45–74 years in the Singapore Chinese Health Study, using Cox regression analysis. RESULTS Risk of incident type 2 diabetes significantly increased beginning with BMIs 18.5–23.0 kg/m2(relative risk 2.47 [95% CI 1.75–3.48]) and continued in a monotonic fashion across the spectrum of BMI. Results were stronger for younger than for older adults. CONCLUSIONS BMIs considered lean and normal in Singaporean Chinese are strongly associated with increased risk of incident type 2 diabetes. This association weakened with advanced age but remained significant.
IFN-γ and Fas/FasL are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2 therapy
Authors: Jon M. Wigginton, Eilene Gruys, Lisa Geiselhart, Jeffrey Subleski, Kristin L. Komschlies, Jong-Wook Park, Theresa A. Wiltrout, Kunio Nagashima, Timothy C. Back, Robert H. Wiltrout
Journal: Journal of Clinical Investigation (2001)

Systemic administration of IL-12 and intermittent doses of IL-2 induce complete regression of metastatic murine renal carcinoma. Here, we show that overt tumor regression induced by IL-12/pulse IL-2 is preceded by recruitment of CD8+ T cells, vascular injury, disrupted tumor neovascularization, and apoptosis of both endothelial and tumor cells. The IL-12/IL-2 combination synergistically enhances cell surface FasL expression on CD8+ T lymphocytes in vitro and induces Fas and FasL expression within tumors via an IFN-γ–dependent mechanism in vivo. This therapy also inhibits tumor neovascularization and induces tumor regression by mechanisms that depend critically on endogenous IFN-γ production and an intact Fas/FasL pathway. The ability of IL-12/pulse IL-2 to induce rapid destruction of tumor-associated endothelial cells and regression of established metastatic tumors is ablated in mice with a dysregulated Fas/FasL pathway. The common, critical role for endogenous IFN-γ and the Fas/FasL pathway in early antiangiogenic effects and in antitumor responses suggests that early, cytokine-driven innate immune mechanisms and CD8+ T cell–mediated responses are interdependent. Definition of critical early molecular events engaged by IL-12/IL-2 may provide new perspective into optimal therapeutic engagement of a productive host-antitumor immune response.
A Randomized Controlled Trial of 7-Day Intensive and Standard Weekly Cognitive Therapy for PTSD and Emotion-Focused Supportive Therapy
Authors: Anke Ehlers, Ann Hackmann, Nick Grey, Jennifer Wild, Sheena Liness, Idit Albert, Alicia Deale, Richard Stott, David M. Clark
Journal: American Journal of Psychiatry (2014)

Psychological treatments for posttraumatic stress disorder (PTSD) are usually delivered once or twice a week over several months. It is unclear whether they can be successfully delivered over a shorter period of time. This clinical trial had two goals: to investigate the acceptability and efficacy of a 7-day intensive version of cognitive therapy for PTSD and to investigate whether cognitive therapy has specific treatment effects by comparing intensive and standard weekly cognitive therapy with an equally credible alternative treatment.Patients with chronic PTSD (N=121) were randomly allocated to 7-day intensive cognitive therapy for PTSD, 3 months of standard weekly cognitive therapy, 3 months of weekly emotion-focused supportive therapy, or a 14-week waiting list condition. The primary outcomes were change in PTSD symptoms and diagnosis as measured by independent assessor ratings and self-report. The secondary outcomes were change in disability, anxiety, depression, and quality of life. Evaluations were conducted at the baseline assessment and at 6 and 14 weeks (the posttreatment/wait assessment). For groups receiving treatment, evaluations were also conducted at 3 weeks and follow-up assessments at 27 and 40 weeks after randomization. All analyses were intent-to-treat.At the posttreatment/wait assessment, 73% of the intensive cognitive therapy group, 77% of the standard cognitive therapy group, 43% of the supportive therapy group, and 7% of the waiting list group had recovered from PTSD. All treatments were well tolerated and were superior to waiting list on nearly all outcome measures; no difference was observed between supportive therapy and waiting list on quality of life. For primary outcomes, disability, and general anxiety, intensive and standard cognitive therapy were superior to supportive therapy. Intensive cognitive therapy achieved faster symptom reduction and comparable overall outcomes to standard cognitive therapy.Cognitive therapy for PTSD delivered intensively over little more than a week was as effective as cognitive therapy delivered over 3 months. Both had specific effects and were superior to supportive therapy. Intensive cognitive therapy for PTSD is a feasible and promising alternative to traditional weekly treatment.
Validation Studies for Models Projecting the Risk of Invasive and Total Breast Cancer Incidence
Authors: J. P. Costantino, M. H. Gail, D. Pee, S. Anderson, C. K. Redmond, J. Benichou, H. S. Wieand
Journal: JNCI Journal of the National Cancer Institute (1999)

In 1989, Gail and colleagues developed a model for estimating the risk of breast cancer in women participating in a program of annual mammographic screening (designated herein as model 1). A modification of this model to project the absolute risk of developing only invasive breast cancer is referred to herein as model 2. We assessed the validity of both models by employing data from women enrolled in the Breast Cancer Prevention Trial.We used data from 5969 white women who were at least 35 years of age and without a history of breast cancer. These women were in the placebo arm of the trial and were screened annually. The average follow-up period was 48.4 months. We compared the observed number of breast cancers with the predicted numbers from the models.In terms of absolute risk, the ratios of total expected to observed numbers of cancers (95% confidence intervals [CIs]) were 0.84 (0. 73-0.97) for model 1 and 1.03 (0.88-1.21) for model 2, respectively. Within the age groups of 49 years or less, 50-59 years, and 60 years or more, the ratios of expected to observed numbers of breast cancers (95% CIs) for model 1 were 0.91 (0.73-1.14), 0.96 (0.73-1. 28), and 0.66 (0.52-0.86), respectively. Thus, model 1 underestimated breast cancer risk in women more than 59 years of age. For model 2, the risk ratios (95% CIs) were 0.93 (0.72-1.22), 1.13 (0.83-1.55), and 1.05 (0.80-1.41), respectively. Both models exhibited a tendency to overestimate risk for women classified in the higher quintiles of predicted 5-year risk and to underestimate risk for those in the lower quintiles of the same.Despite some limitations, these methods provide useful information on breast cancer risk for women who plan to participate in an annual mammographic screening program.
Colonoscopy at a combined district general hospital and specialist endoscopy unit: lessons from 505 consecutive examinations
Authors: S. Thomas-Gibson, C. Thapar, S. G Shah, B. P Saunders
Journal: Journal of the Royal Society of Medicine (2002)

Provisional reports from the Intercollegiate British Society of Gastroenterology National Colonoscopy audit show completion rates of 57–77%for the procedure and poor levels of training and supervision. We prospectively audited all aspects of colonoscopy performed at a combined district general hospital and specialist endoscopy unit. Details of referral, examination, endoscopist, complications and follow-up were recorded and patients were sent questionnaires for long-term follow-up. 505 patients (246 male) underwent colonoscopy by 27 different endoscopists. Their median age was 57 years (range 13–92) and 93%were outpatients. 64% patients were symptomatic and 36%were having surveillance or follow-up colonoscopy. The overall caecal intubation rate was 93%, with little difference between surgeons, physicians and experienced trainees (89%, 92%, 94%) and specialist endoscopists (98%). In only one case was an inexperienced trainee (<100 procedures) unsupervised. Pain scores estimated by the endoscopist were well matched with those given by the patient—medians 29 and 26 (maximum 100) respectively. Median satisfaction score was 96 (maximum 100). Polyp pick-up rate was 26.9%and there were 11 new cancers. 16 (3%) minor immediate complications were recorded—5 oversedation, 6 vasovagal attacks, 3 polypectomy haemorrhages and 2 mucosal injuries (neither requiring treatment). 3 patients died within 6 months of follow-up but no death was colonoscopy related. Completion rates in this setting were adequate for all endoscopists studied. Patient satisfaction with the procedure was high and very few immediate or long-term complications were encountered.
Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure: a consensus statement from the American Heart Association and American Diabetes Association
Authors: Tom A. Elasy, Marie Griffin
Journal: Diabetes Care (2004)

The introduction of thiazolidinediones (TZDs) has been greeted with enthusiasm in part because of their ability to lower glucose by addressing an underlying pathological feature of diabetes and because TZDs have the potential to ameliorate several cardiovascular markers. This enthusiasm has been tempered by safety concerns. We, therefore, read with interest the American Diabetes Association/American Heart Association consensus statement (1) regarding …
Apolipoprotein E predicts incident cardiovascular disease risk in women but not in men with concurrently high levels of high-density lipoprotein cholesterol and C-reactive protein
Authors: James P. Corsetti, Ron T. Gansevoort, Stephan J.L. Bakker, GerJan Navis, Charles E. Sparks, Robin P.F. Dullaart
Journal: Metabolism (2012)
Randomized, Multicenter, Open-Label Study of Oxaliplatin Plus Fluorouracil/Leucovorin Versus Doxorubicin As Palliative Chemotherapy in Patients With Advanced Hepatocellular Carcinoma From Asia
Authors: Shukui Qin, Yuxian Bai, Ho Yeong Lim, Sumitra Thongprasert, Yee Chao, Jia Fan, Tsai-Shen Yang, Vajarabhongsa Bhudhisawasdi, Won Ki Kang, Yu Zhou, Jee Hyun Lee, Yan Sun
Journal: Journal of Clinical Oncology (2013)

To determine whether FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) administered as palliative chemotherapy to patients with advanced hepatocellular carcinoma (HCC) provides a survival benefit and efficacy versus doxorubicin.This multicenter, open-label, randomized, phase III study in mainland China, Taiwan, Korea, and Thailand involved 371 patients age 18 to 75 years who had locally advanced or metastatic HCC and were ineligible for curative resection or local treatment. They were randomly assigned at a ratio of one to one to receive either FOLFOX4 (n = 184) or doxorubicin (n = 187). The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR) by RECIST (version 1.0), and safety.At the prespecified final analysis, median OS was 6.40 months with FOLFOX4 (95% CI, 5.30 to 7.03) and 4.97 months with doxorubicin (95% CI, 4.23 to 6.03; P = .07; hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.02). Median PFS was 2.93 months with FOLFOX4 (95% CI, 2.43 to 3.53), and 1.77 months with doxorubicin (95% CI, 1.63 to 2.30; P < .001; HR, 0.62; 95% CI, 0.49 to 0.79). RR was 8.15% with FOLFOX4 and 2.67% with doxorubicin (P = .02). On continued follow-up, the trend toward increased OS with FOLFOX4 was maintained (P = .04; HR, 0.79; 95% CI, 0.63 to 0.99). Toxicity was consistent with previous experiences with FOLFOX4; proportions of grade 3 to 4 adverse events were similar between treatments.Although the study did not meet its primary end point, the trend toward improved OS with FOLFOX4, along with increased PFS and RR, suggests that this regimen may confer some benefit to Asian patients, but an OS benefit cannot be concluded from these data.
Total prosthetic replacement of atrioventricular valves in the dog: Part III. Local tissue reactions in the heart caused by tricuspid valve prostheses
Authors: G. den Otter
Journal: Thorax (1972)

The metal parts of cardiac valve prostheses cause reactions in the surrounding tissues of the heart. In some dogs rather abnormal reactions were found, and were attributed to corrosion of the stainless steel in the cage of the valve with subsequent local metallosis of the heart and microscopic symptoms of corrosion disease.
Appraisal, assessment and career development for doctors in training: the Mersey Deanery personal development portfolio
Authors: J S Sprigge, J Higgins, B Rice, L Tofield, D Graham
Journal: Journal of the Royal Society of Medicine (2006)

ObjectivesTo develop a robust valid and exportable appraisal and assessment process for doctors in training which is portfolio based and works at all hospitals within the deanery. It is called the personal development portfolio. DesignFor every senior house officer, there was a recorded meeting with his or her supervisor, at the beginning, midterm and at the end of the post. An outside assessor witnessed the exit assessment meeting. SettingThe Wirral Hospital, a District General Hospital with 72 senior house officers in 10 different specialties was used as a pilot site to develop the process. Then the process was exported and implemented at the other 12 trusts of the deanery. Main outcome measuresRecords were kept of the induction, midterm and exit assessment meetings. A record was kept of the number of senior house officers succeeding and failing at their exit assessments. Also, the number promoted to the specialist registrar grade was recorded. ResultsThe process was performed every 6 months on 11 occasions between 2000 and 2005. It involved 72 senior house officers in 10 different specialties. On each occasion, participation usually exceeded 70%: 623 were appraised and assessed and 609 of them (97.8%) had satisfactory exit assessments. For 14 doctors (2.2%), the process identified a cause for concern, which was usually accepted by the doctor and sometimes allowed remedial action to be taken. Twenty-six (4.2%) were promoted to the specialist registrar grade in this period. The process also identified the strengths and weaknesses of the senior house officer posts in the 10 different specialties that had such posts, and was used to encourage good medical teaching practice in them. Over 4 years, we exported the process to all the other 12 Trusts in the Mersey Deanery. Once established, the process was easy to use for both trainees and trainers, although it was time consuming. ConclusionsIt was possible to develop and implement a portfolio based appraisal and assessment process, which was accepted by senior house officers and their trainers in all specialties at all hospitals within the deanery. Now that the senior house officer grade has been superceded by the Foundation and the training grade years, the principles of the personal development portfolio are being used to appraise and assess doctors in these grades too.
Identification and functional prediction of mitochondrial complex III and IV mutations associated with glioblastoma
Authors: Rhiannon E. Lloyd, Kathleen Keatley, D. Timothy J. Littlewood, Brigitte Meunier, William V. Holt, Qian An, Samantha C. Higgins, Stavros Polyzoidis, Katie F. Stephenson, Keyoumars Ashkan, Helen L. Fillmore, Geoffrey J. Pilkington, John E. McGeehan
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM) is the most common primary brain tumor in adults, with a dismal prognosis. Treatment is hampered by GBM's unique biology, including differential cell response to therapy. Although several mitochondrial abnormalities have been identified, how mitochondrial DNA (mtDNA) mutations contribute to GBM biology and therapeutic response remains poorly described. We sought to determine the spectrum of functional complex III and IV mtDNA mutations in GBM. The complete mitochondrial genomes of 10 GBM cell lines were obtained using next-generation sequencing and combined with another set obtained from 32 GBM tissues. Three-dimensional structural mapping and analysis of all the nonsynonymous mutations identified in complex III and IV proteins was then performed to investigate functional importance. Over 200 mutations were identified in the mtDNAs, including a significant proportion with very low mutational loads. Twenty-five were nonsynonymous mutations in complex III and IV, 9 of which were predicted to be functional and affect mitochondrial respiratory chain activity. Most of the functional candidates were GBM specific and not found in the general population, and 2 were present in the germ-line. Patient-specific maps reveal that 43% of tumors carry at least one functional candidate. We reveal that the spectrum of GBM-associated mtDNA mutations is wider than previously thought, as well as novel structural-functional links between specific mtDNA mutations, abnormal mitochondria, and the biology of GBM. These results could provide tangible new prognostic indicators as well as targets with which to guide the development of patient-specific mitochondrially mediated chemotherapeutic approaches.
Erythropoietin-induced antinatriuresis mediated by angiotensin II in perfused kidneys.
Authors: M E Brier, C M Bunke, P V Lathon, G R Aronoff
Journal: Journal of the American Society of Nephrology (1993)

Erythropoietin (EPO)-induced hypertension is a common complication of EPO usage. The hypothesis that erythropoietin is antinatriuretic and that the sodium retention is mediated by intrarenal angiotensin II production was tested. Experiments were performed in Wistar rat kidneys perfused for 60 min in an isolated system. A dose-response curve was performed for EPO at 0, 10, 100, 1,000, and 10,000 mU/mL. EPO administration resulted in a dose-dependent decrease in sodium excretion to a maximum of 50% at the 1,000 mU/mL dose. In a second experiment, kidneys from five groups were perfused: controls, EPO (100 mU/mL), captopril (50 ng/mL), captopril (50 ng/mL) plus EPO (100 mU/mL), and the angiotensin receptor antagonist losartan (1 nM) plus EPO (100 mU/mL). The administration of EPO resulted in an immediate decrease in average sodium excretion (30%) with no change in GFR or other renal function parameters. Pretreatment with captopril or losartan blocked the effect of EPO. Captopril alone had no effect on renal function. A final experiment demonstrated the ability of losartan (10 nM) to block the pressor effects of angiotensin II (0.01, 0.1, and 1 nM). It was concluded that EPO acts within the kidney to cause the production of angiotensin II, which mediates the increased reabsorption of sodium.