tbuckley/cabot-search huggingface dataset:
Influence of energy and nitrogen contents of enteral diets on nitrogen balance: a double blind prospective controlled clinical trial.
Authors: R G Rees, T M Cooper, R Beetham, P G Frost, D B Silk
Journal: Gut (1989)

Results of recent controlled studies show that because of difficulties in administering adequate quantities of enteral diet, positive nitrogen balance is not consistently achieved during enteral feeding. In order to determine whether nitrogen balance can be improved in routine clinical practice by prescribing enteral diets containing higher concentrations of nutrients, 118 patients with normal gastrointestinal function needing enteral nutrition were randomised to receive daily 21 of one of three polymeric diets: Standard diet (1.0 kcal/ml; 6.3 gN/l), Energy Dense diet (1.5 kcal/ml; 7.8 gN/l), and Energy-Nitrogen Dense diet (1.5 kcal/ml; 9.4 gN/l. The three diets, administered by continuous nasogastric infusion, were equally well tolerated. Results were analysed only for patients fed five or more days and who received at least 60% of prescribed enteral diet (n = 42). Positive nitrogen balance was achieved only in the patients receiving the Energy-Nitrogen Dense diet (n = 16; + 1.6 (SE) 0.6 gN/d, compared with the Standard diet (n = 12; -3.8 (1.1) gN/d; p less than 0.001), and the Energy Dense diet (m = 14; -1.9 (0.8) gN/d; p less than 0.005). As the findings of this prospective controlled trial show that positive nitrogen balance was not consistently achieved by administering 21 enteral diet containing up to 15.6 gN, consideration could, therefore, be given to routinely using enteral diets containing up to 9.4 gN/l.
Comparative effects in vivo of recombinant murine interleukin 3, natural murine colony-stimulating factor-1, and recombinant murine granulocyte-macrophage colony-stimulating factor on myelopoiesis in mice.
Authors: H E Broxmeyer, D E Williams, S Cooper, R K Shadduck, S Gillis, A Waheed, D L Urdal, D C Bicknell
Journal: Journal of Clinical Investigation (1987)

Purified murine colony-stimulating factors (CSF) recombinant interleukin 3 (IL-3), natural CSF-1, and recombinant granulocyte-macrophage (GM) CSF were assessed in vivo for their effects on BDF1 mouse bone marrow and spleen granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells in untreated mice and in mice pretreated with purified iron-saturated human lactoferrin (LF). The CSF and LF preparations did not contain detectable endotoxin (less than 0.1 ng). Mice pretreated with LF were more sensitive to the effects of CSF. In mice pretreated with LF, 2,000 U IL-3 or 20,000 U CSF-1 significantly enhanced the cycling status and absolute numbers of all progenitors, whereas 20,000 U GM-CSF significantly increased the cycling status of CFU-GM and CFU-GEMM, but had no effect on cycling of BFU-E or on numbers of any of the progenitors. The effects of CSF in mice pretreated with LF were not mimicked by 0.1-100 ng E. coli lipopolysaccharide.
Multicenter Development and Validation of a Risk Stratification Tool for Ward Patients
Authors: Matthew M. Churpek, Trevor C. Yuen, Christopher Winslow, Ari A. Robicsek, David O. Meltzer, Robert D. Gibbons, Dana P. Edelson
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Most ward risk scores were created using subjective opinion in individual hospitals and only use vital signs.Objectives: To develop and validate a risk score using commonly collected electronic health record data.Methods: All patients hospitalized on the wards in five hospitals were included in this observational cohort study. Discrete-time survival analysis was used to predict the combined outcome of cardiac arrest (CA), intensive care unit (ICU) transfer, or death on the wards. Laboratory results, vital signs, and demographics were used as predictor variables. The model was developed in the first 60% of the data at each hospital and then validated in the remaining 40%. The final model was compared with the Modified Early Warning Score (MEWS) using the area under the receiver operating characteristic curve and the net reclassification index (NRI).Measurements and Main Results: A total of 269,999 patient admissions were included, with 424 CAs, 13,188 ICU transfers, and 2,840 deaths occurring during the study period. The derived model was more accurate than the MEWS in the validation dataset for all outcomes (area under the receiver operating characteristic curve, 0.83 vs. 0.71 for CA; 0.75 vs. 0.68 for ICU transfer; 0.93 vs. 0.88 for death; and 0.77 vs. 0.70 for the combined outcome; P value < 0.01 for all comparisons). This accuracy improvement was seen across all hospitals. The NRI for the electronic Cardiac Arrest Risk Triage compared with the MEWS was 0.28 (0.18–0.38), with a positive NRI of 0.19 (0.09–0.29) and a negative NRI of 0.09 (0.09–0.09).Conclusions: We developed an accurate ward risk stratification tool using commonly collected electronic health record variables in a large multicenter dataset. Further study is needed to determine whether implementation in real-time would improve patient outcomes.
Cellular Microtransport Processes: Intercellular, Intracellular, and Aggregate Behavior
Authors: Johannes M. Nitsche
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Ionic and molecular transfer among cells occurs by a variety of transport processes operative at different length scales. Cell membrane permeability and electrical conductance derive from channel proteins producing pores at the molecular (ultrastructural) scale. Intracellular mobility involves the dynamics of motion through the complex ultrastructure of the cytoplasm. These phenomena unite in the larger-scale (microscopic) process of gross intercellular transfer. When such movement occurs among sufficiently many cells, it in turn begins to reflect their average collective (macroscopic) behavior as bulk tissue. This article surveys selected aspects of intercellular and intracellular transport, with emphasis on detailed mechanistic theory, experimental probes of cellular permeability, and systematic transcendence from small to large length scales.
Use of the Robson classification to assess caesarean section trends in 21 countries: a secondary analysis of two WHO multicountry surveys
Authors: Joshua P Vogel, Ana Pilar Betrán, Nadia Vindevoghel, João Paulo Souza, Maria Regina Torloni, Jun Zhang, Özge Tunçalp, Rintaro Mori, Naho Morisaki, Eduardo Ortiz-Panozo, Bernardo Hernandez, Ricardo Pérez-Cuevas, Zahida Qureshi, A Metin Gülmezoglu, Marleen Temmerman
Journal: The Lancet Global Health (2015)
Coronary Calcification Improves Cardiovascular Risk Prediction in the Elderly
Authors: Rozemarijn Vliegenthart, Matthijs Oudkerk, Albert Hofman, Hok-Hay S. Oei, Wim van Dijck, Frank J.A. van Rooij, Jacqueline C.M. Witteman
Journal: Circulation (2005)

Background— Coronary calcification detected by electron beam tomography may improve cardiovascular risk prediction. The technique is particularly promising in the elderly because the predictive power of cardiovascular risk factors weakens with age. We investigated the prognostic value of coronary calcification for cardiovascular events and mortality in a general, asymptomatic population of elderly subjects. Methods and Results— From 1997 to 2000, electron beam tomography scanning to assess coronary calcification was performed in subjects of the population-based Rotterdam Study. Risk factors were measured by standardized procedures. Coronary calcium scores were available for 1795 asymptomatic participants (mean age, 71 years; range, 62 to 85 years). During a mean follow-up of 3.3 years, 88 cardiovascular events, including 50 coronary events, occurred. The risk of coronary heart disease increased with increasing calcium score. The multivariate-adjusted relative risk of coronary events was 3.1 (95% CI, 1.2 to 7.9) for calcium scores of 101 to 400, 4.6 (95% CI, 1.8 to 11.8) for calcium scores of 401 to 1000, and 8.3 (95% CI, 3.3 to 21.1) for calcium scores &gt;1000 compared with calcium scores of 0 to 100. The predictive value in subjects &gt;70 years of age was similar. Risk prediction based on the cardiovascular risk factors improved when coronary calcification was added. Conclusions— Coronary calcification is a strong and independent predictor of coronary heart disease, also in the elderly. Coronary calcification improves prediction of coronary events based on cardiovascular risk factors. Risk stratification by assessment of coronary calcification may have an important role in the primary prevention of coronary heart disease events in the elderly.
Theoretical medicine: the pathogenesis of osteoarthritis
Authors: P D Byers
Journal: Annals of the Rheumatic Diseases (1988)

Background: E-Cadherin is a putative marker of good prognosis in endometrial cancer. Paradoxically, in a previous study of endometrial carcinoma we found that E-Cadherin is significantly co-expressed with molecular markers of proliferation, usually associated with a worse prognosis in most tumor types. Patients and Methods: The expression of estrogen (ER) and progesterone receptors (PR), Ki67, Human Epidermal Growth Factor Receptor 2 (HER-2, c-ERB-B2), p53 and E-Cadherin was studied by means of immunohistochemistry in 126 endometrial carcinoma samples. The results were correlated with patient survival and included in a multivariate model, in order to identify factors independently associated with the patient outcome. Results: E-Cadherin overexpression was associated with a significantly better overall survival in the whole group of patients with endometrial carcinoma (p=0.012), as well as in the group of patients exclusively harboring endometrioid tumors (p=0.004). In a restricted multivariate model, only tumor stage and E-Cadherin expression retained their independent prognostic power, both for the whole group of tumors (p=0.04), as well as for the subgroup of endometrioid carcinomas (p=0.05). Conclusion: E-Cadherin is an independent predictor of survival in endometrial carcinoma, regardless of histological variety. Proliferation, on the other hand, does not seem to play a prominent role in this same context. This may explain why E-Cadherin retains its prognostic power, despite being significantly co-expressed with all tested molecular proliferation markers.
Outpatient clinic: where is the delay?
Authors: S. Gordon, B. Chappell
Journal: Journal of the Royal Society of Medicine (2003)

Mr Patel and his colleagues (December 2002 JRSM1) discuss the pattern of work in a urology outpatient clinic. It is disturbing that so little time (4.8 minutes) is actually spent with the patient during consultations, and more so that this has decreased so much in the recent past. A notable observation is that 27% of patients did not keep their appointments. If they had, the workload would have been even greater. If the missing patients had arrived and had required on average the same amount of time with the consultant, then the clinic would have been 51 minutes longer—or, if the clinic could not be extended, the time spent with each patient would come down to only 3.5 minutes. This strengthens the arguments of the authors regarding improving efficiencies and investment in staff and training.
Molecular Pathways: Targeting the Cyclin D–CDK4/6 Axis for Cancer Treatment
Authors: Todd VanArsdale, Chris Boshoff, Kim T. Arndt, Robert T. Abraham
Journal: Clinical Cancer Research (2015)

Cancer cells bypass normal controls over mitotic cell-cycle progression to achieve a deregulated state of proliferation. The retinoblastoma tumor suppressor protein (pRb) governs a key cell-cycle checkpoint that normally prevents G1-phase cells from entering S-phase in the absence of appropriate mitogenic signals. Cancer cells frequently overcome pRb-dependent growth suppression via constitutive phosphorylation and inactivation of pRb function by cyclin-dependent kinase (CDK) 4 or CDK6 partnered with D-type cyclins. Three selective CDK4/6 inhibitors, palbociclib (Ibrance; Pfizer), ribociclib (Novartis), and abemaciclib (Lilly), are in various stages of development in a variety of pRb-positive tumor types, including breast cancer, melanoma, liposarcoma, and non-small cell lung cancer. The emerging, positive clinical data obtained to date finally validate the two decades-old hypothesis that the cyclin D-CDK4/6 pathway is a rational target for cancer therapy.
Dietary and Supplemental Calcium Intake and Cardiovascular Disease Mortality
Authors: Qian Xiao, Rachel A. Murphy, Denise K. Houston, Tamara B. Harris, Wong-Ho Chow, Yikyung Park
Journal: JAMA Internal Medicine (2013)

Calcium intake has been promoted because of its proposed benefit on bone health, particularly among the older population. However, concerns have been raised about the potential adverse effect of high calcium intake on cardiovascular health.
Ectopic expression of KCNE3 accelerates cardiac repolarization and abbreviates the QT interval
Authors: Reza Mazhari, H. Bradley Nuss, Antonis A. Armoundas, Raimond L. Winslow, Eduardo Marbán
Journal: Journal of Clinical Investigation (2002)

Regulatory subunit KCNE3 (E3) interacts with KCNQ1 (Q1) in epithelia, regulating its activation kinetics and augmenting current density. Since E3 is expressed weakly in the heart, we hypothesized that ectopic expression of E3 in cardiac myocytes might abbreviate action potential duration (APD) by interacting with Q1 and augmenting the delayed rectifier current (I(K)). Thus, we transiently coexpressed E3 with Q1 and KCNE1 (E1) in Chinese hamster ovary cells and found that E3 coexpression increased outward current at potentials by > or = -80 mV and accelerated activation. We then examined the changes in cardiac electrophysiology following injection of adenovirus-expressed E3 into the left ventricular cavity of guinea pigs. After 72 hours, the corrected QT interval of the electrocardiogram was reduced by approximately 10%. APD was reduced by >3-fold in E3-transduced cells relative to controls, while E-4031-insensitive I(K) and activation kinetics were significantly augmented. Based on quantitative modeling of a transmural cardiac segment, we demonstrate that the degree of QT interval abbreviation observed results from electrotonic interactions in the face of limited transduction efficiency and that heterogeneous transduction of E3 may actually potentiate arrhythmias. Provided that fairly homogeneous ectopic ventricular expression of regulatory subunits can be achieved, this approach may be useful in enhancing repolarization and in treating long QT syndrome.
Combined PET/MRI Improves Diagnostic Accuracy in Patients with Prostate Cancer: A Prospective Diagnostic Trial
Authors: Markus Hartenbach, Sabrina Hartenbach, Winfried Bechtloff, Burkhardt Danz, Klaus Kraft, Burkhard Klemenz, Christoph Sparwasser, Marcus Hacker
Journal: Clinical Cancer Research (2014)

The pretherapeutic assessment of prostate cancer is challenging and still holds the risk of over- or undertreatment. This prospective trial investigates positron emission tomography (PET) with [(18)F]fluoroethylcholine (FEC) combined with endorectal magnetic resonance imaging (MRI) for the assessment of primary prostate cancer.Patients with prostate cancer based on needle biopsy findings, scheduled for radical prostatectomy, were assessed by FEC-PET and MRI in identical positioning. After prostatectomy, imaging results were compared with histologic whole-mount sections, and the PET/MRI lesion-based semiquantitative FEC uptake was compared with biopsy Gleason scores and postoperative histology.PET/MRI showed a patient-based sensitivity of 95% (36/38; 95% confidence interval (CI), 82%-99%). The analysis of 128 prostate lesions demonstrated a sensitivity/specificity/positive predictive value/negative predictive value/accuracy of 67%/35%/59%/44%/54% (P = 0.8295) for MRI and 85%/45%/68%/69%/68% (P = 0.0021) for PET, which increased to 84%/80%/85%/78%/82% (P < 0.0001) by combined FEC-PET/MRI in lesions >5 mm (n = 98). For lesions in patients with Gleason >6 tumors (n = 43), MRI and PET achieved 73%/31%/71%/33%/60% (P = 1.0000) and 90%/62%/84%/73%/81% (P = 0.0010), which were improved to 87%/92%/96%/75%/88% (P < 0.0001) by combined PET/MRI. Applying semiquantitative PET analysis, carcinomas with Gleason scores >6 were distinguished from those with Gleason ≤ 6 with a specificity of 90% and a positive predictive value of 83% (P = 0.0011; needle biopsy 71%/60%, P = 0.1071).In a prospective diagnostic trial setting, combined FEC-PET/MRI achieved very high sensitivity in the detection of the dominant malignant lesion of the prostate, and markedly improved upon PET or MRI alone. Noninvasive Gleason score assessment was more precise than needle biopsy in this patient cohort. Hence, FEC-PET/MRI merits further investigation in trials of randomized, multiarm design.
Effect of diet on creatinine clearance and excretion in young and elderly healthy subjects and in patients with renal disease.
Authors: S W Lew, J P Bosch
Journal: Journal of the American Society of Nephrology (1991)

Thirty-seven young healthy subjects with normal renal function were studied to assess the quantitative effect of protein intake on creatinine clearance. A standard 24-h urine collection and blood sample at the end of the collection were obtained for creatinine and urea concentrations. Correlations between creatinine clearance and urinary urea nitrogen excretion (r = 0.8; P less than 0.0001) and calculated protein intake (r = 0.8; P less than 0.0001) were observed. A significant relationship between creatinine clearance and urea nitrogen excretion was also demonstrated in 28 elderly healthy subjects and 33 patients with renal disease. To demonstrate a cause and effect between urea nitrogen excretion and creatinine clearance in healthy subjects, 18 of the 37 healthy subjects repeated the 24-h urine collection and blood sample after ingesting 5 g of urea in addition to their usual diet. Mean urinary urea nitrogen excretion increased from a mean value of 9.8 +/- 4.0 to 11.8 +/- 4.0 g/day. There was a strong correlation between the changes in urea nitrogen excretion and the changes in creatinine clearance. In acute studies with oral protein loading, there was a significant correlation between creatinine clearance and urinary urea nitrogen excretion. It was concluded that protein intake has a direct and quantitative effect on creatinine clearance in healthy subjects. In normal humans, it is likely that GFR is not a fixed function. Thus, a low creatinine clearance is not a categorical sign of renal disease. A low creatinine clearance adjusted for urea nitrogen excretion may be a useful clinical tool to assess renal function.
Tobacco Smoking as a Risk Factor in Anal Carcinoma: an Antiestrogenic Mechanism?
Authors: M. Frisch, B. Glimelius, J. Wohlfahrt, H.-O. Adami, M. Melbye
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Human papillomavirus-associated anogenital carcinogenesis depends on poorly defined cofactors. Smoking was recently suggested to increase the risk of anal cancer more in premenopausal women than in postmenopausal women. Thus, we used our population-based anal cancer case-control study in Denmark and Sweden to test this hypothesis. METHODS: Our study included 417 patients (324 women and 93 men) who were diagnosed with anal cancer (84% invasive cancer) from 1991 through 1994; it also included five patients diagnosed in 1995. Two control groups were used: 1) 554 population control subjects (349 women and 205 men) and 2) 534 patients with rectal adenocarcinoma (343 women and 191 men). Odds ratios (ORs), calculated from logistic regression analyses, were used as measures of relative risk. All P values are two-sided. RESULTS: Compared with the risk for lifelong nonsmokers, the risk of anal cancer was high among premenopausal women who currently smoked tobacco (multivariate OR = 5.6; 95% confidence interval [CI] = 2.4-12.7) and increased linearly by 6.7% per pack-year smoked (one pack-year is equivalent to one pack of cigarettes smoked per day for 1 year) (P for trend <.001). Smoking was not statistically significantly associated with anal cancer risk in postmenopausal women or men. Women whose menstrual periods started late were at high risk (multivariate OR = 3.6; 95% CI = 1.8-7.3, for ⩾17 years of age versus ⩽12 years of age; P for trend <.001), and body mass index (weight in kg/[height in m]2) was inversely associated with risk among women (P<.001). CONCLUSIONS: Because the risk of anal cancer associated with smoking was restricted to premenopausal women and because higher risk was associated with late menarche and lean body composition, female sex hormones may be a factor in anal cancer development in women. Since the anal mucosa is an estrogen-sensitive area, we hypothesize an antiestrogenic mechanism of action for smoking in anal carcinogenesis.
Effect of nifedipine and AQ-A 39 on the sinoatrial and atrioventricular nodes of the rabbit and their antiarrhythmic action on atrioventricular nodal reentrant tachycardia
Authors: J. SENGES, I. RIZOS, J. BRACHMANN, G. ANDERS, R. JAUERNIG, H.-D. HAMMAN, W. KUBLER
Journal: Cardiovascular Research (1983)

The effects of two drugs that apparently block slow inward current--nifedipine and the new compound AQ-A 39--were studied on the isolated sinoatrial (SA) and atrioventricular (AV) nodes of the rabbit heart using intracellular microelectrodes. Nifedipine and AQ-A 39 both slowed the sinus rate associated with a decrease in the rate of diastolic depolarisation. Conduction through the AV node was consistently impaired; this effect was enhanced with increasing atrial rates or with decreasing coupling intervals of premature beats. The action potential amplitude was significantly reduced in SA nodal and upper (AN) AV nodal fibres but was not significantly affected in lower (NH) AV nodal and in atrial fibres. The maximum diastolic potential showed little or no alteration. In all fibre types studied, the action potential duration was shortened with nifedipine but was significantly prolonged with AQ-A 39. Prevention of AV nodal reentrant tachycardia by nifedipine was related to an increase in the effective refractory period of the AV node. AQ-A 39 prevented the tachycardia by both slowing of AV nodal conduction and by prolongation of action potential duration in the AV nodal and atrial compartments of the reentrant circuit associated with the appearance of different gap phenomena of the AV conduction. The maximum possible A-H interval was, however, not shortened by either drug and single atrial echo beats could still be initiated. The results suggest that nifedipine and AQ-A 39 both have a direct depressant action on the slow inward current-dependent electrical activity of the SA and AV node but have opposite effects on the repolarisation phase resulting in different antiarrhythmic mechanisms.