tbuckley/cabot-search huggingface dataset:
Pentamidine Aerosol Versus Trimethoprim-Sulfamethoxazole for <i>Pneumocystis carinii</i> in Acquired Immune Deficiency Syndrome
Authors: A. Bruce Montgomery, David W. Feigal, Fred Sattler, Gregory R. Mason, Antonio Catanzaro, Robin Edison, Norman Markowitz, Edward Johnson, Sharon Ogawa, Michael Rovzar, Stephen A. Udem, Edward Eden, Newton Hyslop, Tony W. Cheung, Harold Kessler, Donna Mildvan, Jose A. Giron, Neil Ettinger, Clyde Crumpacker, Peter Frame, Neil Steigbigel, Charles Van Der Horst, Martin Hirsch, Michael M. Lederman, Ross G. Hewitt, Robert Fallat, Harrison W. Farber, Henry S. Sacks, Scott A. Eisman, John M. Luce, Tom Boylan, Michael Adams, Judith Feinberg, Philip C. Hopewell
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Pneumocystis carinii pneumonia remains one of the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Treatment with either intravenous pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) is frequently complicated by serious adverse reactions. This study was a prospective, blinded comparison of 600 mg/d of pentamidine as an aerosol versus 15 mg/kg/d of trimethoprim plus 75 mg/kg/d of sulfamethoxazole for patients with mild or moderately severe P. carinii pneumonia (alveolar arterial oxygen difference of less than 55 mm Hg). Of 367 participants who were randomized to receive study therapies, 287 had proven and 16 had presumed Pneumocystis pneumonia. There were 29 deaths within 35 d of study initiation: 12 in the aerosolized pentamidine group and 17 in the TMP-SMX groups (log rank p = 0.28). The difference in mortality was 3.4% (95% CI = − 3.5, 10.8%). Ninety-four patients treated with aerosolized pentamidine had to have their study therapy changed because of lack of efficacy, compared with 22 patients treated with TMP-SMX (p = 0.002). In addition PaO2 improved faster in patients treated with TMP-SMX. However, aerosolized pentamidine was discontinued less often than TMP-SMX because of toxicity (9.4 versus 40% p < 0.001). Rash (0.6 versus 14.9%), nausea and vomiting (1.7 versus 12.2%), and abnormalities of liver function tests (1.7 versus 12.2%) were the most common adverse effects necessitating treatment discontinuation. During 6-mo follow-up there was no difference in mortality. Recurrences of P. carinii pneumonia were more frequent in patients treated with aerosolized pentamidine. Although aerosolized pentamidine was better tolerated than TMP-SMX, patients treated with TMP-SMX showed treatment failure, less often showed more rapidly improved oxygenation, and relapsed less often.
Maternal mild hyperphenylalaninaemia: an international survey of offspring outcome
Authors: H.L Levy, S.E Waisbren, D Lobbregt, E Allred, A Leviton, A Schuler, F.K Trefz, S.M Schwietzer, I.B Sardharwalla, J.H Walter, B.E Barwell, C.M Berlin
Journal: The Lancet (1994)
Prognostic Value of Resting Heart Rate on Cardiovascular and Renal Outcomes in Type 2 Diabetic Patients
Authors: Aurelie Miot, Stéphanie Ragot, Wala Hammi, Pierre-Jean Saulnier, Philippe Sosner, Xavier Piguel, Florence Torremocha, Richard Marechaud, Samy Hadjadj
Journal: Diabetes Care (2012)

OBJECTIVE Epidemiological studies and randomized clinical trials have demonstrated in various populations that resting heart rate (RHR) was an independent predictor of cardiovascular (CV) risk and all-cause mortality. However, few data specifically evaluated the relationship between RHR and long-term CV and renal complications in a large population of type 2 diabetic (T2D) patients. RESEARCH DESIGN AND METHODS We performed a single-center, prospective analysis in 1,088 T2D patients. RHR was determined at baseline by electrocardiogram. The primary outcome was a composite criterion of CV and renal morbi-mortality (CV death, nonfatal myocardial infarction and/or stroke, hospitalization for heart failure, renal replacement therapy), which was adjusted for death from non-CV cause as a competing event. The secondary outcome was a renal composite criterion (renal replacement therapy or doubling of baseline serum creatinine) adjusted for all-cause death as a competing event. RESULTS During median follow-up of 4.2 years, 253 patients (23%) and 62 patients (6%) experienced the primary and secondary outcomes, respectively. In the subgroup of patients with CV disease history at baseline (n = 336), RHR was found to be associated with the incidence of primary outcome (P = 0.0002) but also with renal risk alone, adjusted for all-cause death as a competing event (secondary outcome; P &amp;lt; 0.0001). In patients without history of CV disease, no relation was found between RHR and the incidence of CV and/or renal events. CONCLUSIONS In the real-life setting, RHR constitutes an easy and less time-consuming factor that would permit identification of CV disease diabetic patients with an increased risk for long-term CV and renal complications.
N<scp>UTRITION AND</scp> P<scp>REVENTION OF</scp> T<scp>YPE</scp> 2 D<scp>IABETES</scp>
Authors: T. Costacou, E.J. Mayer-Davis
Journal: Annual Review of Nutrition (2003)

In recent years, the prevalence of type 2 diabetes has increased alarmingly worldwide, giving diabetes the dimension of an epidemic. Striking parallel increases in the prevalence of obesity reflect the importance of body fatness as a contributing factor to diabetes incidence. Moreover, it has been estimated that up to 75% of the risk of type 2 diabetes is attributable to obesity. Recent clinical trials and observational epidemiologic studies demonstrate the efficacy of lifestyle changes, including decreased energy intake, decreased fat intake, and weight loss, as well as regular participation in physical activity, in improving insulin sensitivity (SI) and reducing the risk of diabetes. This review evaluates evidence of the effect of diet on insulin resistance, insulin secretion, and glucose tolerance, and reflects on directions for future work toward primary prevention of type 2 diabetes.
Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus
Authors: D A Isenberg, C McClure, V Farewell, M Spellerberg, W Williams, G Cambridge, F Stevenson
Journal: Annals of the Rheumatic Diseases (1998)

The hemolytic anemia-producing properties of sulfapyridine, sulfamerazine and sulfadiazine have been evaluated in mice by determining the percentage incidence of anemia produced by various concentrations of sulfonamide in the blood. The concentration of sulfonamide in the blood necessary to produce a 50 per cent incidence of anemia was found to be: with sulfapyridine, 2.8 mgm., with sulfadiazine, 33.0 mgm., and with sulfamerazine, 31.0 mgm. per 100 cc. Although a high micromolar concentration of sulfonamide within the erythrocytes was required to produce anemia with sulfadiazine and sulfamerazine, sulfapyridine produced the same incidence of anemia with an erythrocytic concentration only about one-tenth as great. The possible clinical significance of these findings is discussed.
CVID-associated TACI mutations affect autoreactive B cell selection and activation
Authors: Neil Romberg, Nicolas Chamberlain, David Saadoun, Maurizio Gentile, Tuure Kinnunen, Yen Shing Ng, Manmeet Virdee, Laurence Menard, Tineke Cantaert, Henner Morbach, Rima Rachid, Natalia Martinez-Pomar, Nuria Matamoros, Raif Geha, Bodo Grimbacher, Andrea Cerutti, Charlotte Cunningham-Rundles, Eric Meffre
Journal: Journal of Clinical Investigation (2013)

Common variable immune deficiency (CVID) is an assorted group of primary diseases that clinically manifest with antibody deficiency, infection susceptibility, and autoimmunity. Heterozygous mutations in the gene encoding the tumor necrosis factor receptor superfamily member TACI are associated with CVID and autoimmune manifestations, whereas two mutated alleles prevent autoimmunity. To assess how the number of TACI mutations affects B cell activation and tolerance checkpoints, we analyzed healthy individuals and CVID patients carrying one or two TACI mutations. We found that TACI interacts with the cleaved, mature forms of TLR7 and TLR9 and plays an important role during B cell activation and the central removal of autoreactive B cells in healthy donors and CVID patients. However, only subjects with a single TACI mutation displayed a breached immune tolerance and secreted antinuclear antibodies (ANAs). These antibodies were associated with the presence of circulating B cell lymphoma 6-expressing T follicular helper (Tfh) cells, likely stimulating autoreactive B cells. Thus, TACI mutations may favor CVID by altering B cell activation with coincident impairment of central B cell tolerance, whereas residual B cell responsiveness in patients with one, but not two, TACI mutations enables autoimmune complications.
Estrogen binding by leukocytes during phagocytosis,.
Authors: S J Klebanoff
Journal: The Journal of Experimental Medicine (1977)

Estradiol binds covalently to normal leukocytes during phagocytosis. The binding involves three cell types, neutrophils, eosinophils, and monocytes and at least two reaction mechanisms, one involving the peroxidase of neutrophils and monocytes (myeloperoxidase [MPO]) and possibly the eosinophil peroxidase, and the second involving catalase. Binding is markedly reduced when leukocytes from patients with chronic granulomatous disease (CGD), severe leukocytic glucose 6-phosphate dehydrogenase deficiency, and familial lipochrome histiocytosis are employed and two populations of neutrophils, one which binds estradiol and one which does not, can be demonstrated in the blood of a CGD carrier. Leukocytes from patients with hereditary MPO deficiency also bind estradiol poorly although the defect is not as severe as in CGD. These findings are discussed in relation to the inactivation of estrogens during infection and the possible role of estrogens in neutrophil function.
The α-melanocyte stimulating hormone-related tripeptide K(D)PT stimulates human hair follicle pigmentation<i>in situ</i>under proinflammatory conditions
Authors: K.C. Meyer, T. Brzoska, C. Abels, R. Paus
Journal: British Journal of Dermatology (2009)

Background α‐Melanocyte stimulating hormone (α‐MSH) is a well‐tolerated immunomodulator with cytoprotective and anti‐inflammatory effects that is known to stimulate melanogenesis and proliferation of follicular melanocytes. As human hair follicles (HFs) locally synthesize α‐MSH, pharmacologically more easily handled α‐MSH‐related tripeptides, such as K(D)PT, may imitate this endogenous regulation, and may show a favourable side‐effect profile on clinical use. Objectives To investigate the effect of the synthetic, α‐MSH‐related peptide K(D)PT [which is identical to interleukin (IL)‐1β193–195] on melanogenesis in human anagen HFs, under normal and proinflammatory growth conditions. Methods Normal human anagen VI scalp HFs were microdissected and organ cultured with different concentrations of K(D)PT with or without coadministration of a proinflammatory, catagen‐inducing stimulus, interferon (INF)‐γ. Masson–Fontana histochemistry and NKI/beteb immunohistochemistry were employed to assess changes in the degree of human HF pigmentation and melanocyte dendricity. Results As confirmed by quantitative (immuno‐)histomorphometry, compared with controls, K(D)PT alone did not affect human HF pigmentation in organ culture. However, in the presence of a strong, prototypic proinflammatory stimulus (IFN‐γ), K(D)PT significantly stimulated HF melanin content and melanocyte dendrite formation in situ. Conclusions The IL‐1β‐ and α‐MSH‐related tripeptide, K(D)PT, displays interesting hair pigmentation‐stimulatory activities under proinflammatory conditions. These might become exploitable for innovative antigreying strategies, notably in postinflammatory poliosis (regrowth of white hair, e.g. during recovery from alopecia areata), where no effective clinical therapy is yet available.
Concussion and chronic traumatic encephalopathy: International Rugby Board’s response
Authors: Martin Raftery
Journal: British Journal of Sports Medicine (2013)

Concussion and the potential threat of associated chronic traumatic encephalopathy (CTE) have attracted unprecedented media attention. The public debate regarding the link between CTE and head injuries in sport is emotive as well as distracting. This media focus has been positive in that it has raised public awareness of concussion but the same media focus could have negative consequences by



Dr Patricios and Dr Kemp have called for leadership from Rugby in this area and have also called for collision sports to unite and provide a unified, unemotive and consistent message regarding possible neurocognitive effects associated with concussion in sport.

The International Rugby Board (IRB) supports this call for collision sport unity and outlines below an overview of our risk management strategy related to concussion.

The risk of long-term neurodegenerative illness following head injury is unknown.1 This uncertainty is the fuel that fires the public debate. The lack of concrete evidence allows both sides to publically claim a position that is neither supported nor refuted by science.

What we do know is that a single moderate-to-severe traumatic brain injury (TBI) can lead not only to acute neurological deficits but also to long-term neurodegenerative issues, in 40–50% of patients.2 We also know that repetitive head injuries in boxers and recently within other sports have been linked with long-term neurological sequelae.3 ,4 

What we do not know is

Is there a link between concussion (mild TBI) …
Cross-Sectional Association of Kidney Function with Valvular and Annular Calcification
Authors: Caroline S. Fox, Martin G. Larson, Ramachandran S. Vasan, Chao-Yu Guo, Helen Parise, Daniel Levy, Eric P. Leip, Christopher J. O’Donnell, Ralph B. D’Agostino, Emelia J. Benjamin
Journal: Journal of the American Society of Nephrology (2005)

Valvular calcification is common in the setting of end-stage kidney disease and is associated with increased risks for cardiovascular disease events. It is unknown whether the prevalence of valvular calcification is increased in milder kidney disease after accounting for cardiovascular risk factors. Participants who attended the sixth examination of the Framingham Offspring Study (1995 to 1998) were eligible. Kidney function was estimated by GFR using the simplified Modification of Diet in Renal Disease Study equation. Mitral annular calcification (MAC), aortic sclerosis, and aortic annular calcification were assessed by two-dimensional echocardiography. Logistic regression was used to examine the odds of valvular calcification among participants with chronic kidney disease (CKD; GFR < 60 ml/min per 1.73 m2). A total of 3047 participants (52% women; mean age 59 ± 10 yr) were available for analysis. CKD was present in 8.6% (n = 262) of the sample. Among participants with valve/annular calcification (n = 284; 9.3%), 20% had CKD, compared with 7% in patients without valvular calcification. After adjustment for age, gender, systolic and diastolic BP, hypertension treatment, total/HDL cholesterol, body mass index, diabetes, smoking status, and cardiovascular disease, participants with CKD had a 60% increased odds of MAC (odds ratio 1.6; 95% confidence interval 1.03 to 2.5). There was no significant association between CKD and either aortic sclerosis or aortic annular calcification (odds ratio 1.1 and 1.1, respectively). After age and gender adjustment, the combination of both CKD and MAC was associated with a three–fold increased risk for death compared with those with neither condition (P = 0.0004). In the community, CKD is associated with presence of MAC before the onset of ESRD. Further research is warranted to understand whether traditional and novel vascular risk factor burden, as well as metabolic derangements found in early kidney disease, can account for the CKD–MAC association.
Reproducibility of the flow-volume loop.
Authors: A Shaw, J Fisher
Journal: Thorax (1980)

Reproducibility of the flow-volume loopSir,-We read with interest the paper by Macdonald and Cole in your January issue' and congratulate the authors on an important piece of work.There is, however, a vital aspect of reproducibility of res- piratory measurements which was not mentioned.This is the ability or otherwise of the instrument to produce a consistent reading.Although most differ- entiating spirometers produce good results for volume-based measurements such as forced vital capacity, their precision at specific flows is not usually so good.This can mean that the ability of a subject
Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression
Authors: Limin Xia, Wenjie Huang, Dean Tian, Lin Zhang, Xingshun Qi, Zhangqian Chen, Xin Shang, Yongzhan Nie, Kaichun Wu
Journal: Hepatology (2013)

Forkhead box Q1 (FoxQ1) is a master regulator of tumor metastasis. However, the molecular mechanism of FoxQ1 in regulating hepatocellular carcinoma (HCC) metastasis remains unknown. Here we report a novel function for FoxQ1 in modifying the tumor microenvironment to promote HCC metastasis. FoxQ1 expression was an independent and significant risk factor for the recurrence and survival in two independent cohorts totaling 1,002 HCC patients. FoxQ1 induced epithelial-mesenchymal transition (EMT) through the transactivation of ZEB2 expression by directly binding to the ZEB2 promoter. Knockdown of ZEB2 decreased FoxQ1-enhanced HCC metastasis, whereas up-regulation of ZEB2 rescued the decreased metastasis induced by FoxQ1 knocking down. Additionally, serial deletion, site-directed mutagenesis, and a chromatin immunoprecipitation assays showed that VersicanV1, which promoted HCC metastasis and macrophage attraction, was a direct transcriptional target of FoxQ1. FoxQ1-induced VersicanV1 expression promoted the secretion of chemokine (C-C motif) ligand 2 (CCL2) from HCC cells. Chemotaxis assay showed that the culture media from FoxQ1-overexpressing HCC cells increased the migratory activity of the macrophages. Inhibition of VersicanV1 and CCL2 expression significantly inhibited FoxQ1-mediated macrophage migration. In animal studies, the up-regulation of FoxQ1 in HCC cells promoted HCC metastasis and intratumoral tumor associated macrophage (TAM) infiltration, whereas knockdown of VersicanV1 reduced FoxQ1-mediated HCC metastasis and intratumoral TAM infiltration. Depletion of macrophages using clodronate liposomes dramatically decreased FoxQ1-enhanced HCC metastasis. In human HCC tissues, FoxQ1 expression was positively correlated with ZEB2 and VersicanV1 expression and intratumoral TAM infiltration. Patients with positive coexpression of FoxQ1 and ZEB2, FoxQ1, and VersicanV1, or FoxQ1 and intratumoral TAMs were associated with poorer prognosis. FoxQ1 promotes HCC metastasis by transactivating ZEB2 and VersicanV1 expression, resulting in the induction of EMT and the recruitment of macrophage infiltration.
Blood Pressure Trajectories in Early Adulthood and Subclinical Atherosclerosis in Middle Age
Authors: Norrina B. Allen, Juned Siddique, John T. Wilkins, Christina Shay, Cora E. Lewis, David C. Goff, David R. Jacobs, Kiang Liu, Donald Lloyd-Jones
Journal: JAMA (2014)

Single measures of blood pressure (BP) levels are associated with the development of atherosclerosis; however, long-term patterns in BP and their effect on cardiovascular disease risk are poorly characterized.
Selective reticulocyte destruction in erythrocyte pyruvate kinase deficiency
Authors: William C. Mentzer, Robert L. Baehner, Holger Schmidt-Schönbein, Stephen H. Robinson, David G. Nathan
Journal: Journal of Clinical Investigation (1971)

Radioisotope studies of bilirubin turnover, ferrokinetics, and red cell survival ((51)Cr) in a patient with erythrocyte PK deficiency have provided evidence for prompt reticulocyte sequestration and destruction by the reticuloendothelial system. More mature erythrocytes appeared to survive well despite their deficiency of PK. PK-deficient reticulocytes, dependent upon oxidative phosphorylation for ATP production, are exquisitely sensitive to cyanide- or nitrogen-induced mitochondrial inhibition. If oxidative phosphorylation is unavailable, ATP levels decline rapidly, producing alterations in the cell membrane which allow massive losses of potassium and water. The result is a shrunken, spiculated, viscous cell whose rheologic properties would favor its sequestration by the reticuloendothelial system. Those reticulocytes with particularly low levels of PK exhibit very low glycolytic rates and thus are uniquely reliant upon oxidative phosphorylation. Other reticulocytes, better endowed with PK activity, can meet the increased ATP requirements of young erythrocytes. Upon reaching maturity, such cells have diminished ATP needs and can, therefore, survive despite their enzyme deficiency.
Genetic Signatures Reveal High-Altitude Adaptation in a Set of Ethiopian Populations
Authors: Emilia Huerta-Sánchez, Michael DeGiorgio, Luca Pagani, Ayele Tarekegn, Rosemary Ekong, Tiago Antao, Alexia Cardona, Hugh E. Montgomery, Gianpiero L. Cavalleri, Peter A. Robbins, Michael E. Weale, Neil Bradman, Endashaw Bekele, Toomas Kivisild, Chris Tyler-Smith, Rasmus Nielsen
Journal: Molecular Biology and Evolution (2013)

The Tibetan and Andean Plateaus and Ethiopian highlands are the largest regions to have long-term high-altitude residents. Such populations are exposed to lower barometric pressures and hence atmospheric partial pressures of oxygen. Such "hypobaric hypoxia" may limit physical functional capacity, reproductive health, and even survival. As such, selection of genetic variants advantageous to hypoxic adaptation is likely to have occurred. Identifying signatures of such selection is likely to help understanding of hypoxic adaptive processes. Here, we seek evidence of such positive selection using five Ethiopian populations, three of which are from high-altitude areas in Ethiopia. As these populations may have been recipients of Eurasian gene flow, we correct for this admixture. Using single-nucleotide polymorphism genotype data from multiple populations, we find the strongest signal of selection in BHLHE41 (also known as DEC2 or SHARP1). Remarkably, a major role of this gene is regulation of the same hypoxia response pathway on which selection has most strikingly been observed in both Tibetan and Andean populations. Because it is also an important player in the circadian rhythm pathway, BHLHE41 might also provide insights into the mechanisms underlying the recognized impacts of hypoxia on the circadian clock. These results support the view that Ethiopian, Andean, and Tibetan populations living at high altitude have adapted to hypoxia differently, with convergent evolution affecting different genes from the same pathway.
1208 IMPACT OF TELAPREVIR-BASED TREATMENT REGIMENS ON FATIGUE IN GENOTYPE 1 HCV TREATMENT-NAIVE PATIENTS: RESULTS FROM ADVANCE AND ILLUMINATE STUDIES
Authors: S. Gavart, K.E. Sherman, G. Thai, G. Nuyts, S. McAllister, M. Beumont, D. Luo, N. Adda, C. Wright, A.J. Muir
Journal: Journal of Hepatology (2011)