tbuckley/cabot-search huggingface dataset:
Iron Administration and Clinical Outcomes in Hemodialysis Patients
Authors: Harold I. Feldman, Jill Santanna, Wensheng Guo, Howard Furst, Eunice Franklin, Marshall Joffe, Sue Marcus, Gerald Faich
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. To evaluate the impact of parenteral iron administration on the survival and rate of hospitalization of US hemodialysis patients, a nonconcurrent cohort study of 10,169 hemodialysis patients in the United States in 1994 was conducted. The main outcome measures were patient survival and rate of hospitalization. After adjusting for 23 demographic and comorbidity characteristics among 5833 patients included in multivariable analysis, bills for ≤10 vials of iron over 6 mo showed no adverse effect on survival (adjusted relative risk [RR] = 0.93; 95% confidence interval [CI], 0.84 to 1.02; P = 0.14) when compared with none, but bills for &gt;10 vials showed a statistically significant elevated rate of death (adjusted RR = 1.11; 95% CI, 1.00 to 1.24; P = 0.05). Bills for ≤10 vials of iron over 6 mo also showed no significant association with hospitalization (adjusted RR = 0.92; 95% CI, 0.83 to 1.03; P = 0.15), but bills for &gt;10 vials showed statistically significant elevated risk (adjusted RR = 1.12; 95% CI, 1.01 to 1.25; P = 0.03). Prescribing iron in quantities of ≤10 vials over 6 mo had no association with an elevated risk of death or rate of hospitalization. More intensive dosing was associated with diminished survival and higher rates of hospitalization, even after extensive adjustment for baseline comorbidity. Although these potential risks may be offset by the known elevations in morbidity and mortality associated with anemia, these findings indicate that caution is warranted when prescribing &gt;10 vials (1000 mg) of iron dextran over a period of 6 mo.
What's there in a name: tropical calcific pancreatitis and idiopathic chronic pancreatitis in India
Authors: S. Paliwal, S. Bhaskar, G. V. Rao, D. N. Reddy, G. R. Chandak
Journal: Gut (2010)

Midha et al should be applauded for their comprehensive study on chronic pancreatitis (CP) in India.1 We thank them for validating our earlier observations on idiopathic chronic pancreatitis (ICP) patients.2 Their proposed hypothesis ‘chronic pancreatitis previously classified as tropical calcific pancreatitis (TCP) represented idiopathic chronic pancreatitis in India’ is interesting, as the absence of a known aetiological factor (idiopathic) has been a major diagnostic criterion for TCP. While it is understandable that the classical clinical picture of TCP, that had malnutrition as an important component, is changing due to improved economy, it may not be appropriate to comment retrospectively that …
Efficacy of Macrophage-activating Lipopeptide-2 Combined with Interferon-γ in a Murine Asthma Model
Authors: Henning Weigt, Christina Nassenstein, Thomas Tschernig, Peter F. Mühlradt, Norbert Krug, Armin Braun
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The incidence and prevalence of allergic asthma, caused by Th2-mediated inflammation in response to environmental antigens, is increasing. Epidemiologic data suggest that a lack of Th1-inducing factors may play a pivotal role in the development of this disease. We have previously shown that dendritic cells treated with macrophage-activating lipopeptide-2 (MALP-2) combined with IFN-gamma modulate the Th2 response toward Th1 in an in vitro allergy model.To test in vivo efficacy of this regime, the effects of the substances were evaluated in a mouse model of allergic airway inflammation.Female Balb/c mice were sensitized to ovalbumin, whereas control animals were sham-sensitized with adjuvant only. After 4 weeks, MALP-2 and IFN-gamma or NaCl, respectively, were intratracheally instillated. After inhalational ovalbumin challenge, airway hyperreactivity (AHR) to inhaled methacholine was measured by head-out body plethysmography. The animals were subsequently killed to sample bronchoalveolar lavage fluid and lungs.Sensitized NaCl-treated mice developed marked AHR compared with sham-sensitized animals. This coincided with eosinophilia as well as the amplification of eotaxin and the Th2 cytokines interleukin (IL)-5 and IL-13 in the bronchoalveolar lavage fluid. Treatment of sensitized mice with MALP-2 and IFN-gamma significantly reduced AHR compared with the sensitized, NaCl-treated positive control. Eosinophilia as well as Th2 cytokines were reduced to the levels of unsensitized animals. In contrast, IL-12p70 and neutrophils were markedly increased by treatment with both substances.These data demonstrate the in vivo efficacy of MALP-2 and IFN-gamma to reduce allergic inflammation and AHR in allergic asthma.
"Periodic fever" without fever: two cases of non-febrile TRAPS with mutations in the TNFRSF1A gene presenting with episodes of inflammation or monosymptomatic amyloidosis
Authors: T Kallinich
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS) is caused by dominant mutations in the <i>TNFRSF1A</i> gene. In typical cases TRAPS begins early in childhood and is characterised by high and remittent fever over a period of 1–4 weeks or longer, accompanied by systemic and local inflammation. <b>Case reports:</b> Patient 1 presented with recurrent episodes of weakness, migrating myalgias, arthralgias, exanthema, and chest pain lasting for 1–4 weeks, but without any fever over an initial period of 4 years at least. Diagnosis of TRAPS was confirmed by the heterozygous mutation Y20H in <i>TNFRSF1A</i>. Patient 2, a 23 year old woman never had any symptoms indicative of TRAPS. Genetic evaluation of all members of her family with a TRAPS index patient disclosed the T50M mutation in <i>TNFRSF1A</i>. A medical check up showed proteinuria, and renal biopsy disclosed AA amyloidosis. <b>Conclusions:</b> TRAPS associated mutations can induce considerable inflammation that is not necessarily accompanied by fever. Even monosymptomatic severe amyloidosis can occur in these patients. Genetic counselling and appropriate management to prevent or mitigate amyloidosis may be necessary.
Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension
Authors: Nazzareno Galiè, Joan A. Barberà, Adaani E. Frost, Hossein-Ardeschir Ghofrani, Marius M. Hoeper, Vallerie V. McLaughlin, Andrew J. Peacock, Gérald Simonneau, Jean-Luc Vachiery, Ekkehard Grünig, Ronald J. Oudiz, Anton Vonk-Noordegraaf, R. James White, Christiana Blair, Hunter Gillies, Karen L. Miller, Julia H.N. Harris, Jonathan Langley, Lewis J. Rubin
Journal: New England Journal of Medicine (2015)

Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).
Diseases of the Lymphatics
Authors: B. Monk
Journal: Journal of the Royal Society of Medicine (2003)

The sight of a wheelchair-bound patient with huge lymphoedematous legs being wheeled into the consulting room, limbs wrapped in soggy oozing bandages, lymph dripping on to the floor, is not an encouraging one. For the clinician, whether vascular surgeon, dermatologist or oncologist, there are few spectacular therapeutic rabbits to be pulled out of the hat; for the patient, there has often been a lifetime of increasing disability and frustration. There must be particular disillusionment when patients are pronounced 'cured' of cancer only to find their lives blighted by gross lymphoedema of an arm or leg. No wonder, then, that the subject has not been fashionable.
First detection of livestock-associated meticillin-resistant Staphylococcus aureus CC398 in bulk tank milk in the United Kingdom, January to July 2012
Authors: G K Paterson, J Larsen, E M Harrison, A R Larsen, F J Morgan, S J Peacock, J Parkhill, R N Zadoks, M A Holmes
Journal: Eurosurveillance (2012)

Livestock-associated meticillin-resistant Staphylococcus aureus belonging to clonal complex 398 (LA-MRSA CC398) is an important cause of zoonotic infections in several countries, but there is only a single published report of this lineage from the United Kingdom (UK). Here, we describe the isolation of LA-MRSA CC398 from bulk tank milk from five geographically dispersed farms in the UK. Our findings suggest that LA-MRSA CC398 is established in livestock in the UK. Awareness of the potential occupational risks and surveillance in other food-producing animal species should be promoted.
β-Myosin Heavy Chain Is Induced by Pressure Overload in a Minor Subpopulation of Smaller Mouse Cardiac Myocytes
Authors: Javier E. López, Bat-Erdene Myagmar, Philip M. Swigart, Megan D. Montgomery, Stephen Haynam, Marty Bigos, Manoj C. Rodrigo, Paul C. Simpson
Journal: Circulation Research (2011)

Induction of the fetal hypertrophic marker gene β-myosin heavy chain (β-MyHC) is a signature feature of pressure overload hypertrophy in rodents. β-MyHC is assumed present in all or most enlarged myocytes.To quantify the number and size of myocytes expressing endogenous β-MyHC by a flow cytometry approach.Myocytes were isolated from the left ventricle of male C57BL/6J mice after transverse aortic constriction (TAC), and the fraction of cells expressing endogenous β-MyHC was quantified by flow cytometry on 10,000 to 20,000 myocytes with use of a validated β-MyHC antibody. Side scatter by flow cytometry in the same cells was validated as an index of myocyte size. β-MyHC-positive myocytes constituted 3 ± 1% of myocytes in control hearts (n=12), increasing to 25 ± 10% at 3 days to 6 weeks after TAC (n=24, P<0.01). β-MyHC-positive myocytes did not enlarge with TAC and were smaller at all times than myocytes without β-MyHC (≈70% as large, P<0.001). β-MyHC-positive myocytes arose by addition of β-MyHC to α-MyHC and had more total MyHC after TAC than did the hypertrophied myocytes that had α-MyHC only. Myocytes positive for β-MyHC were found in discrete regions of the left ventricle in 3 patterns: perivascular, in areas with fibrosis, and in apparently normal myocardium.β-MyHC protein is induced by pressure overload in a minor subpopulation of smaller cardiac myocytes. The hypertrophied myocytes after TAC have α-MyHC only. These data challenge the current paradigm of the fetal hypertrophic gene program and identify a new subpopulation of smaller working ventricular myocytes with more myosin.
The microcirculation in experimental hypertension and aging
Authors: P. M. Hutchins, C. D. Lynch, P. T. Cooney, K. A. Curseen
Journal: Cardiovascular Research (1996)

The purpose of this manuscript is to review the literature concerning the alterations in the microvasculature in experimental hypertension and aging. We also present new unpublished data and results where previous studies have not addressed important questions.The new studies were performed using a chronic cranial window to allow multiple observations of the cortical surface vasculature over time. In vivo video, microscopic techniques were used to study long-term changes in microvascular caliber (vasomotion). In some studies, a chronic, in-dwelling aortic catheter allowed chaotic analysis of short-term blood pressure and heart rate variations.In these new studies we demonstrated a reduction in number of small arteriolar endpoints per cortical surface area in the spontaneously hypertensive rat and in the old Brown-Norway rat. There was also a reduction in the number of arteriole-to-arteriole anastomotic connections in the older rat. These vascular changes in the old rat were revised or prevented by caloric restriction. In the old rat, there was also a reduction in the variability of blood pressure, heart rate and microvessel caliber (vasomotion).These studies suggest that there is an alteration in the morphology of the small arterioles in hypertension and aging, that may lead to reduced ability to perfuse cortical tissue. In addition, there appears to be a diminution of overall short-term cardiovascular and microvascular control.
Intraperitoneal Chemotherapy for Ovarian Carcinoma: Results of Long-Term Follow-Up
Authors: R. R. Barakat
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine long-term survival and predictors of recurrence in a retrospective cohort of patients with epithelial ovarian cancer treated with intraperitoneal (IP) chemotherapy. PATIENTS AND METHODS: Records were reviewed of 433 patients who received IP therapy for ovarian cancer between 1984 and 1998; follow-up data were available for 411 patients. IP therapy was provided as consolidation therapy (n = 89), or for treatment of persistent (n = 310) or recurrent (n = 12) disease after surgery and initial systemic therapy; therapy usually consisted of platinum-based combination therapy. Statistical analysis included tests for associations between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox proportional hazard model. RESULTS: The mean age of patients was 52 years (range, 25 to 76 years). Distribution by stage and grade was as follows: stage I, 7; II, 24; III, 342; IV, 52; not available (NA), 8; and grade 1, 30; 2, 99; and 3, 289; NA, 15. The median survival from initiation of IP therapy by residual disease was none, 8.7 years; microscopic, 4.8 years; less than 1 cm, 3.3 years; more than 1 cm, 1.2 years. In a multivariate analysis, the only significant predictors of long-term survival were grade and size of residual disease at initiation of IP therapy. CONCLUSION: Prolonged survival was observed in selected patients receiving IP platinum-based therapy. It is not possible to determine the contribution of IP therapy to survival in this study. A relationship between size of disease at the initiation of IP therapy and long-term survival was demonstrated.
eNOS Deficiency Predisposes Podocytes to Injury in Diabetes
Authors: Darren A. Yuen, Bailey E. Stead, Yanling Zhang, Kathryn E. White, M. Golam Kabir, Kerri Thai, Suzanne L. Advani, Kim A. Connelly, Tomoko Takano, Lei Zhu, Alison J. Cox, Darren J. Kelly, Ian W. Gibson, Takamune Takahashi, Raymond C. Harris, Andrew Advani
Journal: Journal of the American Society of Nephrology (2012)

Endothelial nitric oxide synthase (eNOS) deficiency may contribute to the pathogenesis of diabetic nephropathy in both experimental models and humans, but the underlying mechanism is not fully understood. Here, we studied two common sequelae of endothelial dysfunction in diabetes: glomerular capillary growth and effects on neighboring podocytes. Streptozotocin-induced diabetes increased glomerular capillary volume in both C57BL/6 and eNOS(-/-) mice. Inhibiting the vascular endothelial growth factor receptor attenuated albuminuria in diabetic C57BL/6 mice but not in diabetic eNOS(-/-) mice, even though it inhibited glomerular capillary enlargement in both. In eNOS(-/-) mice, an acute podocytopathy and heavy albuminuria occurred as early as 2 weeks after inducing diabetes, but treatment with either captopril or losartan prevented these effects. In vitro, serum derived from diabetic eNOS(-/-) mice augmented actin filament rearrangement in cultured podocytes. Furthermore, conditioned medium derived from eNOS(-/-) glomerular endothelial cells exposed to both high glucose and angiotensin II activated podocyte RhoA. Taken together, these results suggest that the combined effects of eNOS deficiency and hyperglycemia contribute to podocyte injury, highlighting the importance of communication between endothelial cells and podocytes in diabetes. Identifying mediators of this communication may lead to the future development of therapies targeting endothelial dysfunction in albuminuric individuals with diabetes.
Evidence for Widespread Positive and Purifying Selection Across the European Rabbit (Oryctolagus cuniculus) Genome
Authors: M. Carneiro, F. W. Albert, J. Melo-Ferreira, N. Galtier, P. Gayral, J. A. Blanco-Aguiar, R. Villafuerte, M. W. Nachman, N. Ferrand
Journal: Molecular Biology and Evolution (2012)

The nearly neutral theory of molecular evolution predicts that the efficacy of both positive and purifying selection is a function of the long-term effective population size (Ne) of a species. Under this theory, the efficacy of natural selection should increase with Ne. Here, we tested this simple prediction by surveying ∼1.5 to 1.8 Mb of protein coding sequence in the two subspecies of the European rabbit (Oryctolagus cuniculus algirus and O. c. cuniculus), a mammal species characterized by high levels of nucleotide diversity and Ne estimates for each subspecies on the order of 1 × 106. When the segregation of slightly deleterious mutations and demographic effects were taken into account, we inferred that >60% of amino acid substitutions on the autosomes were driven to fixation by positive selection. Moreover, we inferred that a small fraction of new amino acid mutations (<4%) are effectively neutral (defined as 0 < Nes < 1) and that this fraction was negatively correlated with a gene's expression level. Consistent with models of recurrent adaptive evolution, we detected a negative correlation between levels of synonymous site polymorphism and the rate of protein evolution, although the correlation was weak and nonsignificant. No systematic X chromosome–autosome difference was found in the efficacy of selection. For example, the proportion of adaptive substitutions was significantly higher on the X chromosome compared with the autosomes in O. c. algirus but not in O. c. cuniculus. Our findings support widespread positive and purifying selection in rabbits and add to a growing list of examples suggesting that differences in Ne among taxa play a substantial role in determining rates and patterns of protein evolution.
Reconstructing the ubiquitin network - cross-talk with other systems and identification of novel functions
Authors: Thiago M Venancio, S Balaji, Lakshminarayan M Iyer, L Aravind
Journal: Genome biology (2009)

The ubiquitin system (Ub-system) can be defined as the ensemble of components including Ub/ubiquitin-like proteins, their conjugation and deconjugation apparatus, binding partners and the proteasomal system. While several studies have concentrated on structure-function relationships and evolution of individual components of the Ub-system, a study of the system as a whole is largely lacking. Using numerous genome-scale datasets, we assemble for the first time a comprehensive reconstruction of the budding yeast Ub-system, revealing static and dynamic properties. We devised two novel representations, the rank plot to understand the functional diversification of different components and the clique-specific point-wise mutual-information network to identify significant interactions in the Ub-system. Using these representations, evidence is provided for the functional diversification of components such as SUMO-dependent Ub-ligases. We also identify novel components of SCF (Skp1-cullin-F-box)-dependent complexes, receptors in the ERAD (endoplasmic reticulum associated degradation) system and a key role for Sus1 in coordinating multiple Ub-related processes in chromatin dynamics. We present evidence for a major impact of the Ub-system on large parts of the proteome via its interaction with the transcription regulatory network. Furthermore, the dynamics of the Ub-network suggests that Ub and SUMO modifications might function cooperatively with transcription control in regulating cell-cycle-stage-specific complexes and in reinforcing periodicities in gene expression. Combined with evolutionary information, the structure of this network helps in understanding the lineage-specific expansion of SCF complexes with a potential role in pathogen response and the origin of the ERAD and ESCRT systems.
Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.
Authors: R O Bonow, A L Picone, C L McIntosh, M Jones, D R Rosing, B J Maron, E Lakatos, R E Clark, S E Epstein
Journal: Circulation (1985)

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- 3% in those with normal ejection fraction (n = 30). Patients with subnormal left ventricular ejection fraction and poor exercise tolerance or prolonged duration of left ventricular dysfunction (greater than 18 months) comprised the high-risk subgroup (5 year survival 52 +/- 11%). Patients in this subgroup also had persistent left ventricular dysfunction after operation, with greater left ventricular end-diastolic dimensions and reduced ejection fraction (both p less than .001) compared with patients with normal preoperative left ventricular ejection fraction or a brief duration of left ventricular dysfunction (less than 14 months). Cold hyperkalemic cardioplegia was used for myocardial preservation in 46 patients.(ABSTRACT TRUNCATED AT 250 WORDS)