tbuckley/cabot-search huggingface dataset:
Pathophysiology of Edema Formation in Children with Nephrotic Syndrome Not Due to Minimal Change Disease
Authors: JOHAN G. J. VANDE WALLE, RAYMOND A. DONCKERWOLCKE, HEIN A. KOOMANS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. It has been shown that children with nephrotic syndrome due to minimal change disease (MCD) can present with avid salt retention and stimulated vasoactive hormones, as well as with stable edema. The present study examines these conditions in children with nephrotic syndrome not due to MCD (non-MCD). In six children with hypovolemic symptoms (congenital nephrotic syndrome in four), strong sodium retention (fractional sodium excretion, FE Na , 0.2 ± 0.2%) was found. Lithium clearance (FE Li ) and maximal water excretion ( V max ) were suppressed, suggesting avid sodium reabsorption throughout the nephron. Aldosterone, renin, and norepinephrine were elevated. Sixteen other children with non-MCD had stable edema. FE Na was 1.8 ± 1.1%, whereas FE Li , V max , and hormones were normal, and not different from data in 35 nonproteinuric children. In children with MCD, 12 presented with hypovolemic symptoms and strong sodium retention (FE Na 0.3 ± 0.3%), whereas 15 were stable (FE Na 1.1 ± 0.7%). Regarding tubular sodium handling and hormones, the same distinction could be made as for the children with non-MCD. However, hypoproteinemia differed. In the children with non-MCD lesions, plasma colloid osmotic pressure was significantly lower in the hypovolemic types (4.2 ± 0.4 mmHg) than in those with stable edema (13.0 ± 3.8 mmHg; P &lt; 0.05); in MCD, no such difference existed (respectively, 8.1 ± 3.0 and 9.9 ± 2.2 mmHg). In summary, children with nephrotic syndrome may present with pathophysiologic pictures of decreased effective circulating volume or of stable edema, regardless of whether they have non-MCD or MCD. The pathogenesis of the hypovolemic picture seems to be different, since it is associated with extreme hypoproteinemia only in the children with non-MCD.
A Prospective Study of Symptomatic Hypoglycemia in Young Diabetic Patients
Authors: David E Goldstein, Jack D England, Randall Hess, Sharon S Rawlings, Beth Walker
Journal: Diabetes Care (1981)

The frequency of symptomatic hypoglycemia was determined prospectively over an 18-mo period in 147 children and adolescents with diabetes mellitus. All patients were treated with two daily injections of insulin. The data were analyzed to determine the relationship between episodes of symptomatic hypoglycemia and blood glucose control as assessed by hemoglobin A1c measurements. There were 542 patient visits during the study period. During each clinic visit, patients were separated into one of four hypoglycemic categories based on the medical history since the preceding visit. These categories were: no reactions, mild to occasional reactions, mild to frequent reactions, and severe reactions. Reactions were considered severe if they were characterized by altered central nervous system function or prolonged sympathetic nervous system symptoms. Forty-seven percent of the patients reported at least one reaction during the 18-mo study period, but only 4% (i.e., 6 out of 147 patients) reported severe reactions. The mean hemoglobin A1c level was significantly lower in patients who reported reactions than in patients who did not report reactions [hemoglobin A1c values (x¯ ± SEM) = 7.78 ± 0.1% vs. 9.48 ± 0.1%, respectively; P &amp;gt; 0.001]. The severity of hypoglycemia was inversely related to the degree of altered blood glucose control; episodes of frequent or severe symptomatic hypoglycemia occurred almost exclusively in patients with well-controlled diabetes as reflected in their near-normal hemoglobin A1c levels. There were no significant differences in mean insulin dose/kg, age, or duration of diabetes comparing patients in the four hypoglycemic categories. The results indicate that the hemoglobin A1c level can be a useful clinical guide to identify patients who are most likely to develop serious symptomatic hypoglycemia.
Quality of Life at the End of Primary Treatment of Breast Cancer: First Results From the Moving Beyond Cancer Randomized Trial
Authors: P. A. Ganz, L. Kwan, A. L. Stanton, J. L. Krupnick, J. H. Rowland, B. E. Meyerowitz, J. E. Bower, T. R. Belin
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: During the last decade, survival rates for breast cancer have increased as a result of earlier detection and increased use of adjuvant therapy. Limited data exist on the psychosocial aspects of the transitional period between the end of primary treatment and survivorship. We investigated the baseline psychosocial status of women enrolled in a randomized trial testing two psychosocial interventions for women at the end of primary treatment. Methods: Participants, identified within 1 month after surgery (registration), provided demographic information and limited measures of quality of life. They were followed until they finished primary treatment (enrollment), at which time they completed a mailed baseline survey that included standardized measures of quality of life (including standardized scales of physical and emotional functioning), mood, symptoms, and sexual functioning. A total of 558 patients (mean age = 56.9 years) were enrolled in the study between July 1, 1999, and June 30, 2002. Health outcomes were examined according to treatment received: mastectomy with and without chemotherapy, and lumpectomy with and without chemotherapy. All statistical tests were two-sided. Results: Among all treatment groups, patients who had a mastectomy had the poorest physical functioning at registration (P<.001) and at enrollment (P= .05). At enrollment, mood and emotional functioning were similar among all patients, with no differences by type of treatment received. At enrollment, symptoms, including muscle stiffness, breast sensitivity, aches and pains, tendency to take naps, and difficulty concentrating, were common among patients in all groups and were statistically significantly associated with poor physical functioning and emotional well-being. Sexual functioning was worse for women who received chemotherapy than for those who did not, regardless of type of surgery (P<.001). Conclusions: At the end of primary treatment for breast cancer, women in all treatment groups report good emotional functioning but report decreased physical functioning, particularly among women who have a mastectomy or receive chemotherapy. Clinical interventions to address common symptoms associated with treatment should be considered to improve physical and emotional functioning at the end of primary treatment for breast cancer.
Teaching postgraduates about managing drug and alcohol misuse
Authors: Z. Morris-Williams, L. Monrouxe, A. Grant, A. Edwards
Journal: BMJ (2012)

Report from UK medical royal colleges outlines the key competencies 

A working group of the UK medical royal colleges reported recently on the core competencies needed by all postgraduate specialist trainees regarding substance misuse.1 This follows other recent reports, including those from individual royal colleges, parliament, and other stakeholders, that highlight the need to change the system by which we recognise and manage drug and alcohol misuse. Such changes were implemented in the undergraduate curriculum after the International Centre for Drug Policy produced guidance on teaching about substance misuse in 2007.2 However, the knowledge and skills learnt at medical school are not yet part of the core competencies of postgraduate medical training in the United Kingdom.

The increasing use of illicit drugs and the hazardous consumption of alcohol provide a growing challenge for the NHS. In 2009-10, more than one million hospital admissions in England were alcohol related,3 at a cost of almost £3bn (€3.8bn; $4.7bn).4 It is estimated that in England alone, 25% of the adult population (7.6 million people) drink hazardous amounts of alcohol and almost half of them show signs of alcohol related ill health.4 In addition, around 9% of adults questioned as part of the British crime survey 2010-11 admitted to illicit …
Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma
Authors: Hector G. Ortega, Mark C. Liu, Ian D. Pavord, Guy G. Brusselle, J. Mark FitzGerald, Alfredo Chetta, Marc Humbert, Lynn E. Katz, Oliver N. Keene, Steven W. Yancey, Pascal Chanez
Journal: New England Journal of Medicine (2014)

Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids.
Effect of Alzheimer’s Disease Risk Genes on Trajectories of Cognitive Function in the Cardiovascular Health Study
Authors: Robert A. Sweet, Howard Seltman, James E. Emanuel, Oscar L. Lopez, James T. Becker, Joshua C. Bis, Elise A. Weamer, Mary Ann A. DeMichele-Sweet, Lewis H. Kuller
Journal: American Journal of Psychiatry (2012)

Objective The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease. Method The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end. Results The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors. Conclusions Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease.
Decreased myocardial contractility in papillary muscles from atherosclerotic rabbits.
Authors: D W Peterson, D W Griffith, C A Napolitano
Journal: Circulation Research (1979)

To determine the effect atherosclerosis has on myocardial contractility, we studied the contractile properties of right ventricular papillary muscles from 34 atherosclerotic and 17 control rabbits. We produced atherosclerosis by feeding for 2 to 8 months a diet of 5% lard, 5% peanut oil, 0.5% cholesterol, and 89.5% rabbit pellets. The controls received only rabbit pellets during the same time interval. Contracting isometrically 12 times per minute at 25 degrees C, muscles from the atherosclerotic rabbits developed tension at a lower maximum rate (max dT/dt), had a longer latency, and required longer to develop tension at the maximum rate and to develop peak tension. In isotonic contractions, they shortened with lower maximum velocities and required longer to accelerate to maximum velocity and to shorten maximally. We found no evidence that developed tension or distance shortened differed between the two groups of muscles. Raising the contraction frequency to 24 contractions per minute between the two groups of muscles. Raising the contraction frequency to 24 contractions per minute brought performance of the two groups of muscles closer in both types of contraction. Norepinephrine (1.5 x 10-5 M) nearly abolished differences between performance of the two groups. The loss of contractility correlates poorly with coronary and aortic atherosclerosis. It occurred early in the feeding of the atherogenic diet. We think it was due to a lipid-induced defect in the cardiac cell's handling of calcium.
Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene.
Authors: A K Ewart, W Jin, D Atkinson, C A Morris, M T Keating
Journal: Journal of Clinical Investigation (1994)

Supravalvular aortic stenosis (SVAS) is an inherited vascular disease that can cause heart failure and death. SVAS can be inherited as an autosomal dominant trait or as part of a developmental disorder, Williams syndrome (WS). In recent studies we presented evidence suggesting that a translocation disrupting the elastin gene caused SVAS in one family while deletions involving the entire elastin locus caused WS. In this study, pulsed-field, PCR, and Southern analyses showed that a 100-kb deletion of the 3' end of the elastin gene cosegregated with the disease in another SVAS family. DNA sequence analysis localized the breakpoint between elastin exons 27 and 28, the same region disrupted by the SVAS-associated translocation. These data indicate that mutations in the elastin gene cause SVAS and suggest that elastin exons 28-36 may encode critical domains for vascular development.
5-hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial
Authors: Jane T Hickok, Joseph A Roscoe, Gary R Morrow, Christopher W Bole, Hongwei Zhao, Karen L Hoelzer, Shaker R Dakhil, Timothy Moore, Tom R Fitch
Journal: The Lancet Oncology (2005)
Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy
Authors: Valentina Di Foggia, Xinyu Zhang, Danilo Licastro, Mattia F.M. Gerli, Rahul Phadke, Francesco Muntoni, Philippos Mourikis, Shahragim Tajbakhsh, Matthew Ellis, Laura C. Greaves, Robert W. Taylor, Giulio Cossu, Lesley G. Robson, Silvia Marino
Journal: The Journal of Experimental Medicine (2014)

The Polycomb group (PcG) protein Bmi1 is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems. We show that mild up-regulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy. The molecular mechanism underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)-driven modulation of resistance to oxidative stress in the satellite cell population. These results lay the basis for developing Bmi1 pharmacological activators, which either alone or in combination with MT1 agonists could be a powerful novel therapeutic approach to improve regeneration in muscle wasting conditions.
Building Scientific Progress without Borders: Nanobiology and Nanomedicine in China and the U.S.
Authors: Paul C. Wang, Robert P. Blumenthal, Yuliang Zhao, Julie A. Schneider, Nancy Miller, Piotr Grodzinski, Michael M. Gottesman, Sally Tinkle, Kuan Wang, Chen Wang, Xing-Jie Liang
Journal: Cancer Research (2009)

In recent years, growing numbers of nanomaterials and nanotechnology applications have been used as novel imaging, diagnostic, and therapeutic agents in the treatment of cancer and other diseases. The safe and effective development and use of these new nanotechnologies will require coordinated
Molecular Pathways: Emerging Roles of Mammalian Sirtuin SIRT7 in Cancer
Authors: Silvana Paredes, Lidia Villanova, Katrin F. Chua
Journal: Clinical Cancer Research (2014)

SIRT7 belongs to the Sirtuin family of NAD-dependent enzymes, the members of which play diverse roles in aging, metabolism, and disease biology. Increased SIRT7 expression is observed in human cancers and growing evidence suggests important SIRT7 functions in fundamental cellular programs with an impact on oncogenic transformation and tumor biology. SIRT7 associates with chromatin, where it catalyzes selective deacetylation of lysine 18 on histone H3 (H3K18), an emerging epigenetic biomarker of aggressive tumors and poor clinical outcome in patients with cancer. Through H3K18 deacetylation at specific promoters, SIRT7 controls a tumor-suppressive gene expression program that stabilizes the transformed state of cancer cells. SIRT7 also orchestrates several molecular processes, including rRNA and tRNA synthesis, which ultimately promote the increased ribosome biogenesis necessary for tumor cell growth and proliferation. Remarkably, inactivation of SIRT7 can reverse the transformed phenotype of cancer cells and reduce their tumorigenicity in vivo. These findings place SIRT7 at the crossroads of chromatin signaling, metabolic, and tumor-regulatory pathways. Thus, SIRT7 is a promising pharmacologic target for epigenetic cancer therapy. The development of SIRT7 modulators may allow new therapeutic strategies that control tumor progression by reprogramming the chromatin landscape and biosynthetic machinery of cancer cells.
Pretransplant Lung Function, Respiratory Failure, and Mortality after Stem Cell Transplantation
Authors: Tanyalak Parimon, David K. Madtes, David H. Au, Joan G. Clark, Jason W. Chien
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: The role of pulmonary function before stem cell transplant as a potential risk factor for the development of early post-transplant respiratory failure and mortality is controversial. Methods: We conducted a retrospective analysis of the pretransplant pulmonary function of 2,852 patients who received their transplant between 1990 and 2001. Measurements: Pretransplant FEV1, FVC, total lung capacity (TLC), diffusing capacity of carbon monoxide (DLCO), and the alveolar–arterial oxygen tension difference P(A-a)O2 were measured and assessed for association with development of early respiratory failure and mortality in Cox proportional hazard logistic models. Main Results: In multivariate analyses, progressive decrease of all lung function parameters was associated with a stepwise increase in risk of developing early respiratory failure and mortality when assessed in independent models. On the basis of a significant correlation between FEV1 and FVC (r = 0.81), FEV1 and TLC (r = 0.61), and FVC and TLC (r = 0.80), and a lack of correlation between FEV1 and DLCO, we developed a pretransplant lung function score based on pretransplant FEV1 and DLCO to determine the extent of pulmonary compromise before transplant. Multivariate analysis indicated that higher pretransplant lung function scores are associated with a significant increased risk for developing early respiratory failure (category II hazard ratio [HR], 1.4; category III HR, 2.2; category IV HR, 3.1; p < 0.001) and death (category II HR, 1.2; category III HR, 2.2; category IV HR, 2.7; p < 0.005). Conclusions: These results suggest that not only does compromised pretransplant lung function contribute to the risk for development of early respiratory failure and mortality but this risk may be estimated before transplant by grading the extent of FEV1 and DLCO compromise.
Patients' evaluation on asthma severity was related to level of asthma control and quality of life over seven years follow-up
Authors: Anna Ericson, Björn Ställberg, Christer Janson, Josefin Sundh, Scott Montgomery, Mary Kampe, Eva Osterlund Efraimsson
Journal: European Respiratory Journal (2013)

Patients' evaluation on asthma severity was related to level of asthma control and quality of life over seven years follow-up
Spectrum of Mutation and Frequency of Allelic Deletion of the p53 Gene in Ovarian Cancer
Authors: M. F. Kohler, J. R Marks, R. W. Wiseman, I. J. Jacobs, A. M. Davidoff, D. L. Clarke-Pearson, J. T. Soper, R. C. Bast, A. Berchuck
Journal: JNCI Journal of the National Cancer Institute (1993)

The p53 gene encodes a nuclear phosphoprotein present in low levels in normal human cells. The wild-type form of this protein functions to restrain inappropriate cellular proliferation. Approximately one half of human epithelial ovarian cancers have mutations in the p53 gene and overexpress the mutant protein product. Deletion of one allele of the p53 gene also frequently occurs in these cancers.We sought to define the spectrum of mutations in the p53 gene in epithelial ovarian cancer with respect to both the specific codons involved and the type of mutations observed. We also examined the frequency of allelic deletion of the p53 gene in cancers containing p53 gene mutations.Tissue samples from the epithelial ovarian cancers of 62 patients were obtained during initial laparotomy. Histologic examination was done to ensure that the experimental samples used in this study contained more than 75% cancer cells. Total RNA was extracted from these samples and separately from matched control noncancerous regions of the surgical specimen or white blood cells. The purified RNAs were reverse transcribed to generate cDNA copies of exons 4-10 of the p53 gene. Two rounds of polymerase chain reaction (PCR) were conducted to produce enough template for DNA sequence analysis of the regions of interest within the p53 gene. Dideoxy sequencing of at least two independent productions of each amplified DNA template was done to confirm the validity of the mutations found. Allelic deletions were identified by PCR and gel electrophoretic techniques to examine three polymorphisms within the p53 gene in cancer-normal DNA pairs.We identified 45 mutations in exons 5-8 of the p53 gene, where mutations frequently have been found in other cancer types. An additional mutation was identified in exon 4. Overall, 72% of the mutations were transitions, 24% transversions, and 4% microdeletions. Allelic deletion of the other p53 allele was seen in 67% of ovarian cancers in which a p53 mutation was present. Germ-line p53 mutations were not found in any patients whose cancers had p53 mutations.Like p53 mutations in other types of human cancers, those in epithelial ovarian cancers are diverse and occur frequently in exons 5-8. The predominance of transition mutations suggests that p53 mutations in ovarian cancer arise because of spontaneous errors in DNA synthesis and repair rather than the direct interaction of carcinogens with DNA. These molecular data are consistent with data from epidemiologic studies that have failed to demonstrate a convincing relationship between exposure to environmental carcinogens and the development of ovarian cancer.
AN EXPERIMENT IN TEACHING FAMILY DYNAMICS
Authors: ARDEN A. FLINT, MARGARET J. RIOCH
Journal: American Journal of Psychiatry (1963)

The course described in this paper was an important aspect of the first year's work in an experimental program in training psychotherapists. It was unique in that it integrated many different parts into a meaningful ful, lively, learning experience of family dynamics without burdening the beginning students with too heavy a therapeutic responsibility in this difficult field. The good results were recognized by students and instructors. The success of the program as a whole is a further indication that courses of this kind would be useful in the training of psychotherapists of whatever professional affiliation.