tbuckley/cabot-search huggingface dataset:
Thirty years of home mechanical ventilation in children: escalating need for pediatric intensive care beds
Authors: Fleur M. Paulides, Frans B. Plötz, Laura P. Verweij-van den Oudenrijn, Josephus P. J. van Gestel, Mike J. Kampelmacher
Journal: Intensive Care Medicine (2012)

To describe trends in pediatric home mechanical ventilation (HMV) and their impact on the use of pediatric intensive care unit (PICU) beds.Review of all children who had started HMV in a single center for HMV.Between 1979 and 2009, HMV was started in 197 patients [100 (51%) with invasive and 97 with noninvasive ventilation], with a median age of 14.7 (range 0.5-17.9) years. Most patients (77%) were males with a neuromuscular disorder (66%). The number of children receiving HMV increased from 8 in the 1979-1988 period to 122 in the 1999-2008 period. This increase occurred foremost in patients aged 0-5 years and was accompanied by a sharp rise in the use of PICU beds. In 150 patients (76%), HMV was initiated on an ICU with a total of 12,440 admission days, of which 10,385 days (83%) could be attributed to 67 patients who started non-electively with invasive HMV. Of the latter, 52 patients had been admitted to a PICU with a total of 9,335 admission days. At the end of the study, 134 patients (68%) were still being ventilated, 43 patients (22%) had died, 11 patients (6%) were weaned from HMV, 4 patients (2%) did not want to continue HMV and 5 patients (3%) were lost to follow-up.Over time, there was an impressive increase in the application of HMV in children. This increase was most obvious in the youngest age group with invasive HMV, and these children had very long stays in the PICU.
Sodium-lithium exchange in sarcolemmal vesicles from canine superior mesenteric artery.
Authors: A M Kahn, J C Allen, E J Cragoe, R Zimmer, H Shelat
Journal: Circulation Research (1988)

Exchange of intracellular sodium for extracellular lithium readily occurs in vascular smooth muscle, but the mechanism of this exchange is not known. These studies examined whether a sodium-lithium countertransport system was present in the cell membrane of vascular smooth muscle. A sarcolemmal-enriched vesicle preparation was obtained from canine superior mesenteric artery via a magnesium aggregation and differential centrifugation technique. An outwardly directed gradient for lithium stimulated 22Na uptake by the vesicles, and an inwardly directed gradient for lithium stimulated 22Na efflux. These effects were not due to an alteration in membrane potential, and sodium uptake was not stimulated by lithium in the absence of a gradient for lithium. The lithium gradient-stimulated component of sodium uptake was not affected by a change in membrane potential and was insensitive to ouabain. Both sodium-lithium exchange and sodium-proton exchange in sarcolemmal-enriched vesicles were inhibited by two compounds that inhibit the sodium-lithium countertransport system in red cells, phloretin and quinidine. Ethylisopropylamiloride also inhibited both sodium-lithium exchange and sodium-proton exchange in the vesicles. In support of the possibility that sarcolemmal sodium-lithium exchange and sodium-proton exchange are mediated by a single cation exchange mechanism with affinity for sodium, lithium, and protons, we found that an inwardly directed sodium or lithium gradient stimulated proton efflux, and that the stimulation of sodium efflux by external lithium or protons was not additive. It is concluded from these studies that sarcolemmal vesicles from canine superior mesenteric artery contain an electroneutral, phloretin, quinidine, and ethylisopropylamiloride inhibitable sodium-lithium exchange transport system.(ABSTRACT TRUNCATED AT 250 WORDS)
THE INHIBITION OF THE TOXICITY OF URANIUM NITRATE BY SODIUM CARBONATE, AND THE PROTECTION OF THE KIDNEY ACUTELY NEPHROPATHIC FROM URANIUM FROM THE TOXIC ACTION OF AN ANESTHETIC BY SODIUM CARBONATE
Authors: William Deb. MacNider
Journal: The Journal of Experimental Medicine (1916)

1. The toxicity of uranium in animals of different ages is associated with the power of the metal to lead to the formation of organic acids, as, for instance, diacetic acid and also acetone. 2. The power of sodium carbonate to lessen the toxicity of uranium depends upon its power to delay the formation of such bodies and to cause their appearance in the urine in lessened amounts, and does not depend upon the power of the carbonate to detoxicate the metal. 3. The protection of the kidney by the carbonate, which is shown by the kidney being functionally much more active during an anesthesia than the kidney of a control animal, and by the Jack of fatty degeneration, acute swelling, and necrosis of the renal epithelium which is constantly seen in the unprotected kidneys, is probably dependent upon two factors: the neutralization of organic acids formed prior to and during the anesthesia, and the neutralization of hydrochloric acid which Graham has shown to be liberated by chloroform during an anesthesia induced by this substance.
A "DOUBLE BLIND" STUDY COMPARING RO 4-0403, TRIFLUOPERAZINE AND A PLACEBO IN CHRONICALLY ILL MENTAL PATIENTS
Authors: ANTIOCO BARRON, BARBARA BECKERING, LESTER H. RUDY, JACKSON A. SMITH
Journal: American Journal of Psychiatry (1961)

1. RO 4-0403 (Taractan) produced a beneficial response in 7 of a group of 30 extremely chronic psychotic patients. Those patients who responded showed a decrease in agitation, appeared more friendly and expressed the subjective sensation of "feeling better." Undesirable side effects were observed in only 2 of the 30 patients treated. From these results it would appear that this compound can be safely and effectively used in acute psychiatric disorders. 2. Trifluoperazine (Stelazine) is a potent drug that is effective in reducing the symptomatology in chronic psychotic patients. In this study more than half the patients who received trifluoperazine showed a desirable change of behavior during the study but side effects were noted in 40% of those treated. These side effects usually appeared at a high dosage and disappeared promptly after the administration of anti-Parkinsonian drugs. 3. Since only 1 patient out of 30 showed a slight improvement while receiving a placebo, it is presumed that suggestion and attention were of minimal importance in producing the changes observed with the active compounds.
Impact of Carbohydrate Counting on Glycemic Control in Children With Type 1 Diabetes
Authors: Sanjeev N. Mehta, Nicolle Quinn, Lisa K. Volkening, Lori M.B. Laffel
Journal: Diabetes Care (2009)

OBJECTIVE To study the association between parent carbohydrate counting knowledge and glycemic control in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS We assessed 67 youth ages 4–12 years with type 1 diabetes (duration ≥1 year). Parents estimated carbohydrate content of children's meals in diet recalls. Ratios of parent estimates to computer analysis defined carbohydrate counting knowledge; the mean and SD of these ratios defined accuracy and precision, respectively. A1C defined glycemic control. RESULTS Greater accuracy and precision were associated with lower A1C in bivariate analyses (P &amp;lt; 0.05). In a multivariate analysis (R2= 0.25, P = 0.007) adjusting for child age, sex, and type 1 diabetes duration, precision (P = 0.02) and more frequent blood glucose monitoring (P = 0.04), but not accuracy (P = 0.9), were associated with lower A1C. A1C was 0.8% lower (95% CI −0.1 to −1.4) among youth whose parents demonstrated precision. CONCLUSIONS Precision with carbohydrate counting and increased blood glucose monitoring were associated with lower A1C in children with type 1 diabetes.
In Vivo Assessment of Neurotransmitter Biochemistry in Humans
Authors: J R Barrio, S Huang, M E Phelps
Journal: The Annual Review of Pharmacology and Toxicology (1988)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Anomalous Aortic Origin of Coronary Arteries in the Young
Authors: Richard Lorber, Shubhika Srivastava, Travis J Wilder, Susan McIntyre, William M DeCampli, William G Williams, Peter C Frommelt, Ira A Parness, Eugene H Blackstone, Marshall L Jacobs, Luc Mertens, Julie A Brothers, J René Herlong
Journal: JACC. Cardiovascular imaging (2015)
Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies
Authors: Benoit Witkowski, Chanaki Amaratunga, Nimol Khim, Sokunthea Sreng, Pheaktra Chim, Saorin Kim, Pharath Lim, Sivanna Mao, Chantha Sopha, Baramey Sam, Jennifer M Anderson, Socheat Duong, Char Meng Chuor, Walter R J Taylor, Seila Suon, Odile Mercereau-Puijalon, Rick M Fairhurst, Didier Menard
Journal: The Lancet Infectious Diseases (2013)
Response to Comment on Krul-Poel et al. Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial. Diabetes Care 2015;38:1420–1426
Authors: Yvonne H.M. Krul-Poel, Sanne Westra, Suat Simsek
Journal: Diabetes Care (2015)

We thank Bellastella et al. (1) for their interest in our recently published double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes who were treated with either vitamin D3 (50,000 IU/month) or placebo for 6 months (2). These patients were well controlled at baseline (HbA1c was 6.8 ± 0.5% [51 ± 6 mmol/mol] and 6.8 ± 0.5% [51 ± 5 mmol/mol] in the vitamin D and placebo groups, respectively). …
Unrestricted C3 Activation Occurs in Crry-Deficient Kidneys and Rapidly Leads to Chronic Renal Failure
Authors: Lihua Bao, Ying Wang, Anthony Chang, Andrew W. Minto, Jian Zhou, Hong Kang, Mark Haas, Richard J. Quigg
Journal: Journal of the American Society of Nephrology (2007)

Deficiency of the C3 convertase regulator Crry is embryonic lethal in mice unless C3 also is absent. For evaluation of the effect of local kidney Crry deficiency in the setting of an intact complement system, Crry−/−C3−/− mouse kidneys were transplanted into syngeneic C57BL/6 wild-type mice. These Crry-deficient kidneys developed marked inflammatory cell infiltration, tubular damage, and interstitial fibrosis, whereas similar changes were absent in control transplanted kidneys. Strong C3 deposition in the vessels and tubules that correlated significantly with measures of disease supported that complement activation was pathogenic in this model. Microarray studies showed upregulation of a number of chemokine and extracellular matrix genes, which were validated for CCL2 and CXCL10 mRNA and collagen III protein. The functional significance of these pathophysiologic findings was evaluated by removing both native kidneys, so the transplanted kidney alone provided renal function. Within 21 d of transplantation, seven of eight Crry-deficient kidneys in complement-sufficient wild-type hosts failed, compared with two of 13 controls (P = 0.001), with final blood urea nitrogen levels of 133.9 ± 33.0 and 55.6 ± 8.3 mg/dl, respectively (P = 0.015). These data show that mouse Crry is a critical complement regulator in the kidney. When absent, unrestricted complement activation occurs and quickly leads to marked inflammation and progressive renal failure, with features relevant to human diseases with underlying defects in complement regulation, such as hemolytic uremic syndrome.
Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells
Authors: A M Glodek, Y Le, D M Dykxhoorn, S-Y Park, G Mostoslavsky, R Mulligan, J Lieberman, H E Beggs, M Honczarenko, L E Silberstein
Journal: Leukemia (2007)
Multicenter Phase II Study of the Oral MEK Inhibitor, CI-1040, in Patients With Advanced Non-Small-Cell Lung, Breast, Colon, and Pancreatic Cancer
Authors: John Rinehart, Alex A. Adjei, Patricia M. LoRusso, David Waterhouse, J. Randolph Hecht, Ronald B. Natale, Oday Hamid, Mary Varterasian, Peggy Asbury, Eric P. Kaldjian, Stephen Gulyas, David Y. Mitchell, Roman Herrera, Judith S. Sebolt-Leopold, Mark B. Meyer
Journal: Journal of Clinical Oncology (2004)

Purpose This multicenter, open-label, phase II study was undertaken to assess the antitumor activity and safety of the oral mitogen-activated extracellular signal regulated kinase kinase (MEK) inhibitor, CI-1040, in breast cancer, colon cancer, non-small-cell lung cancer (NSCLC), and pancreatic cancer. Patients and Methods Patients with advanced colorectal, NSCLC, breast, or pancreatic cancer received oral CI-1040 continuously at 800 mg bid. All patients had measurable disease at baseline, a performance status of 2 or less, and adequate bone marrow, liver, and renal function. Expression of pERK, pAkt, and Ki-67 was assessed in archived tumor specimens by quantitative immunohistochemistry. Results Sixty-seven patients with breast (n = 14), colon (n = 20), NSCLC (n = 18), and pancreatic (n = 15) cancer received a total of 194 courses of treatment (median, 2.0 courses; range, one to 14 courses). No complete or partial responses were observed. Stable disease (SD) lasting a median of 4.4 months (range, 4 to 18 months) was confirmed in eight patients (one breast, two colon, two pancreas, and three NSCLC patients). Treatment was well tolerated, with 81% of patients experiencing toxicities of grade 2 or less severity. Most common toxicities included diarrhea, nausea, asthenia, and rash. A mild association (P &lt; .055) between baseline pERK expression in archived tumor specimens and SD was observed. Conclusion CI-1040 was generally well tolerated but demonstrated insufficient antitumor activity to warrant further development in the four tumors tested. PD 0325901, a second generation MEK inhibitor, has recently entered clinical development and, with significantly improved pharmacologic and pharmaceutical properties compared with CI-1040, it may better test the therapeutic potential of MEK inhibition in cancer.
Contrasting Roles of Complement Activation and Its Regulation in Membranous Nephropathy
Authors: Patrick N. Cunningham, Richard J. Quigg
Journal: Journal of the American Society of Nephrology (2005)

The complement system is involved in defense against microorganisms, the processing of immune complexes and apoptotic debris, and the development of an appropriate immune response. Along with these physiologic effects, complement activation has the potential to result in tissue pathology. To limit this, various complement regulatory proteins (CRP) are present on host cells, including the glomerular podocyte. Experimental data from the Heymann nephritis (HN) rat model of human membranous nephropathy (MN) have shown that IgG antibodies in subepithelial immune deposits initiate complement activation and C5b-9–mediated damage of the overlying podocyte. Although IgG can activate the classical pathway, there also is evidence that alternative pathway activation occurs in MN, which could occur because of absent, dysfunctional, or inhibited podocyte CRP. Related to this are experimental data in HN showing the presence of antibodies that bind and inhibit podocyte CRP; although such antibodies have not been documented in human MN, a decrease in CR1 quantity on the podocyte has been observed. A s a result of a relative lack of CRP and the exposure of activating complement proteins to tubular cells, alternative complement pathway activation and C5b-9–mediated tubular injury can occur in MN and other proteinuric diseases. Overall, in a disease such as MN, the balance between complement regulation and activation is tipped toward its being activated. Therefore, a number of therapeutic approaches have been developed to counteract this, including recombinant forms of endogenous CRP and complement-inhibitory monoclonal antibodies. There is good reason to be optimistic that approaches to block complement activation will become viable therapy for human MN in the future.
Pharmacogenomics in Asthma Therapy: Where Are We and Where Do We Go?
Authors: Heung-Woo Park, Kelan G. Tantisira, Scott T. Weiss
Journal: The Annual Review of Pharmacology and Toxicology (2014)

The response to drug treatment in asthma is a complex trait and is markedly variable even in patients with apparently similar clinical features. Pharmaco-genomics, which is the study of variations of human genome characteristics as related to drug response, can play a role in asthma therapy. Both a traditional candidate-gene approach to conducting genetic association studies and genome-wide association studies have provided an increasing list of genes and variants associated with the three major classes of asthma medications: β2-agonists, inhaled corticosteroids, and leukotriene modifiers. Moreover, a recent integrative, systems-level approach has offered a promising opportunity to identify important pharmacogenomics loci in asthma treatment. However, we are still a long way away from making this discipline directly relevant to patients. The combination of network modeling, functional validation, and integrative omics technologies will likely be needed to move asthma pharmacogenomics closer to clinical relevance.
Promoter Hypermethylation Is Associated With Tumor Location, Stage, and Subsequent Progression in Transitional Cell Carcinoma
Authors: James W.F. Catto, Abdel-Rahmene Azzouzi, Ishtiaq Rehman, Kenneth M. Feeley, Simon S. Cross, Najla Amira, Gaelle Fromont, Mathilde Sibony, Oliver Cussenot, Mark Meuth, Freddie C. Hamdy
Journal: Journal of Clinical Oncology (2005)

Purpose Transitional cell carcinoma (TCC) is a pan-urothelial disease characterized by multiplicity. Although little is known about the molecular events in upper-tract TCC, similar carcinogenic mechanisms are thought to occur throughout the urinary tract. However, we have previously shown that distinct patterns of microsatellite instability occur in upper and lower urinary tract TCC, suggesting biologic differences between these tumors. Here we investigate the extent of promoter hypermethylation in TCC throughout the urinary tract. Patients and Methods Tissue was obtained from 280 patients (median follow-up, 56 months) whose tumors comprised 116 bladder and 164 upper-tract tumors (UTT). Analysis for hypermethylation at 11 CpG islands, using methylation-sensitive polymerase chain reaction and bisulfite sequencing, was performed for each sample and compared with the tumor's clinicopathologic details, microsatellite instability status, and subsequent behavior. Results Promoter methylation was present in 86% of TCC and occurred both more frequently and more extensively in UTT (94%) than in bladder tumors (76%; P &lt; .0001). Methylation was associated with advanced tumor stage (P = .0001) and higher tumor progression (P = .03) and mortality rates (P = .04), when compared with tumors without methylation. Multivariate analysis revealed that methylation at the RASSF1A and DAPK loci, in addition to tumor stage and grade, were associated with disease progression (P &lt; .04). Conclusion Despite morphologic similarities, there are genetic and epigenetic differences between TCC in the upper and lower urinary tracts. Methylation occurs commonly in urinary tract tumors, may affect carcinogenic mechanisms, and is a prognostic marker and a potential therapeutic target.
Acquisition of cytogenetic abnormalities in patients with IPSS defined lower‐risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia
Authors: Elias Jabbour, Koichi Takahashi, Xuemei Wang, A. Megan Cornelison, Lynne Abruzzo, Tapan Kadia, Gautam Borthakur, Zeev Estrov, Susan O'Brien, Mar Mallo, William Wierda, Sherry Pierce, Yue Wei, Francisco Sole, Rui Chen, Hagop Kantarjian, Guillermo Garcia‐Manero
Journal: American Journal of Hematology (2013)

We hypothesized that the dynamic acquisition of cytogenetic abnormalities (ACA) during the follow up of myelodysplastic syndromes (MDS) could be associated with poor prognosis. We conducted a retrospective analysis of 365 patients with IPSS low or intermediate-1 risk MDS who had at least two consecutive cytogenetic analyses during the follow up. Acquisition of cytogenetic abnormalities was detected in 107 patients (29%). The most frequent alteration involved chromosome 7 in 21% of ACA cases. Median transformation-free and overall survival for patients with and without ACA were 13 vs. 52 months (P = 0.01) and 17 vs. 62 months (P = 0.01), respectively. By fitting ACA as a time-dependent covariate, multivariate Cox regression analysis showed that patients with ACA had increased risk of transformation (HR = 1.40; P = 0.03) or death (HR = 1.45; P = 0.02). Notably, female patients with therapy-related MDS (t-MDS) had an increased risk of developing ACA (OR = 5.26; P < 0.0001), although subgroup analysis showed that prognostic impact of ACA was not evident in t-MDS. In conclusion, ACA occurs in close to one third of patients with IPSS defined lower risk MDS, more common among patients with t-MDS, but has a significant prognostic impact on de novo MDS.
Tetracosactrin for the management of asthmatic patients after long-term corticosteroids.
Authors: P Hugh-Jones, R S Pearson, M Booth
Journal: Thorax (1975)

Thirty-five of 41 asthmatic patients, who had been taking oral corticosteroids regularly for between one and 12 years, recovered their adrenal function after courses of depot tetracosactrin, even those with apparently complete adrenal suppression. They all showed benefit by transfer to depot tetracosactrin, though steroid withdrawal symptoms could be troublesome. Skin pigmentation in three, and two severe reactions to tetracosactrin were encountered. We believe that it is advisable to give depot tetracosactrin when converting severe asthmatics to the use of beclomethasone dipropionate aerosols who have previously been treated by long-term steroids with consequent adrenal suppression.
Positron Emission Tomography for Staging of Pediatric Sarcoma Patients: Results of a Prospective Multicenter Trial
Authors: Thomas Völker, Timm Denecke, Ingo Steffen, Daniel Misch, Stefan Schönberger, Michail Plotkin, Juri Ruf, Christian Furth, Brigitte Stöver, Hubertus Hautzel, Günter Henze, Holger Amthauer
Journal: Journal of Clinical Oncology (2007)

The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients.In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 +/- 12 months), and histopathology and was determined by an interdisciplinary tumor board.FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001).In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.