tbuckley/cabot-search huggingface dataset:
Renal function and biopsy findings after 5 years' treatment with low-dose cyclosporin for psoriasis
Authors: A.V. POWLES, T. COOK, B. HULME, B.S. BAKER, H.M. LEWIS, E. THOMAS, H. VALDIMARSSON, L. FRY
Journal: British Journal of Dermatology (1993)

Renal biopsies were performed in eight patients with chronic plaque psoriasis who had been treated with low-dose cyclosporin (CyA) (range 1-6 mg/kg/day; average dose 3.3 mg/kg/day) for an average period of 5 years. In six of the eight patients biopsies showed features consistent with CyA nephrotoxicity. Tubular atrophy and arteriolar hyalinosis were present in all six, four had an increase in interstitium, and two showed an increased incidence of glomerular obsolescence. Two of the patients showed all of these features, two patients had three features, and the remaining patients had two features. Renal function was assessed by glomerular filtration rate (GFR) and serum creatinine. Both a fall in the GFR and a rise in the serum creatinine correlated with the severity of the features of CyA nephrotoxicity seen on biopsy. However, the best predictor of the biopsy findings was a failure of renal function to show significant improvement when CyA was discontinued for a month. CyA has been discontinued in two of the eight patients who had the most severe features of CyA nephrotoxicity on renal biopsy. In both patients there has been improvement of renal function after 1 year of follow-up.
Treatment of Breast Cancer With Trastuzumab During Pregnancy
Authors: Shubham Pant, Mark B. Landon, Michael Blumenfeld, William Farrar, Charles L. Shapiro
Journal: Journal of Clinical Oncology (2008)

We have long realized that certain oncologists tended to attract particular types of patients and wonder whether this represents a resonance of similar humors.In addition, we postulate that oncologists specializing in certain tumor types tend to fall into particular personality types.We wonder whether this is because of the natural history of the disease and its often limited treatment options; or, is it a reflection of the type of person who chooses to specialize in a particular malignancy?Do oncologists tend to choose malignancies with similar tendencies to their own personalities, or do they choose malignancies whose treatment approach is in keeping with their personality and philosophy?Potentially, imbalances in patient care, (and oncologist well-being) could occur when disease type, and treatment approach, are too well aligned (or too opposed) with oncologist temperament (Table 1).If this theory holds water (or black bile or phlegm...), by identifying their own humidity and temperature, budding oncologists may be able to select the tumor types that they should specialize in.This may provide more reliable career advice than strategic decisions based on likely job opportunities, local expertise, or PhD subject.In addition, by being aware of their own personality type, oncologists can be cognizant of the potential conflict this might generate with the characteristics of the tumor and its treatments.
Scintigraphic Response by <sup>123</sup>I-Metaiodobenzylguanidine Scan Correlates With Event-Free Survival in High-Risk Neuroblastoma
Authors: Howard M. Katzenstein, Susan L. Cohn, Richard M. Shore, Dianna M.E. Bardo, Paul R. Haut, Marie Olszewski, Jennifer Schmoldt, Dachao Liu, Alfred W. Rademaker, Morris Kletzel
Journal: Journal of Clinical Oncology (2004)

Purpose To investigate whether response to induction therapy, evaluated by metaiodobenzylguanadine (MIBG) and bone scintigraphy, correlates with event-free survival (EFS) in children with high-risk neuroblastoma (NB). Patients and Methods Twenty-nine high-risk NB patients were treated prospectively with an intensive induction regimen and consolidated with three cycles of high-dose therapy with peripheral blood stem-cell rescue. The scintigraphic response was evaluated by MIBG and bone scans using a semi-quantitative scoring system. The prognostic significance of the imaging scores at diagnosis and following induction therapy was evaluated. Results A trend associating worse 4-year EFS rates for patients with versus without osteomedullary uptake on MIBG scintigraphs at diagnosis was seen (35% ± 11% v 80% ± 18%, respectively; P = .13). Similarly, patients with positive bone scans at diagnosis had worse EFS than those with negative scans, although the difference did not receive statistical significance (34% ± 10% v 83% ± 15%, respectively; P = .06). However, significantly worse EFS was observed in patients with a postinduction MIBG score of ≥ 3 compared to those with scores of less than 3 (0% v 58% ± 11%; P = .002). There was no correlation between bone scan scores and outcome following induction therapy. Conclusion MIBG scores ≥ 3 following induction therapy identifies a subset of NB patients who are likely to relapse following three cycles of high-dose therapy with peripheral blood stem-cell rescue, local radiotherapy, and 13-cis-retinoic acid. Alternative therapeutic strategies should be considered for patients with a poor response to induction therapy.
Circulatory and Renal Adjustments to Acute Femoral Arteriovenous Fistulas
Authors: Q. R. MURPHY, K. S. GULLIXSON, C. H. KRATOCHVIL, J. SIMOES E. SILVA
Journal: Circulation Research (1958)

This Paper is concerned with the pattern of cardiorespiratory and renal changes produced by opening a systemic arteriovenous fistula. Flow through bilateral femoral arteriovenous fistulas averaged approximately 53 per cent of the control cardiac output. The rise in cardiac output elicited by the shunt averaged 51 per cent of the shunt flow PAH clearances decreased 23 per cent in animals anesthetized with sodium pentobarbital, and 46 per cent in animals premedicated with morphine sulfate prior to administration of sodium pentobarbital. The per cent reduction in renal blood flow did not differ significantly from the per cent reduction in flow through the extrarenal systemic capillary beds.
Hyperglycemia and Renin-Dependent Hypertension Synergize to Model Diabetic Nephropathy
Authors: Bryan R. Conway, Jillian Rennie, Matthew A. Bailey, Donald R. Dunbar, Jonathan R. Manning, Christopher O. Bellamy, Jeremy Hughes, John J. Mullins
Journal: Journal of the American Society of Nephrology (2011)

Rodent models exhibit only the earliest features of human diabetic nephropathy, which limits our ability to investigate new therapies. Hypertension is a prerequisite for advanced diabetic nephropathy in humans, so its rarity in typical rodent models may partly explain their resistance to nephropathy. Here, we used the Cyp1a1mRen2 rat, in which the murine renin-2 gene is incorporated under the Cytochrome P4501a1 promoter. In this transgenic strain, administration of low-dose dietary indole-3-carbinol induces moderate hypertension. In the absence of hypertension, streptozotocin-induced diabetes resulted in a 14-fold increase in albuminuria but only mild changes in histology and gene expression despite 28 weeks of marked hyperglycemia. In the presence of induced hypertension, hyperglycemia resulted in a 500-fold increase in albuminuria, marked glomerulosclerosis and tubulointerstitial fibrosis, and induction of many of the same pathways that are upregulated in the tubulointerstitium in human diabetic nephropathy. In conclusion, although induction of diabetes alone in rodents has limited utility to model human diabetic nephropathy, renin-dependent hypertension and hyperglycemia synergize to recapitulate many of the clinical, histological, and gene expression changes observed in humans.
Perforation of Gastric Carcinoma
Authors: A. W. Adams
Journal: BMJ (1949)

<h3>Abstract</h3> <h3>Background</h3> Accurate network models of species interaction could be used to predict population dynamics and be applied to manage real world ecosystems. Most relevant models are nonlinear, however, and data available from real world ecosystems are too noisy and sparsely sampled for common inference approaches. Here we improved the inference of generalized Lotka-Volterra (gLV) ecological networks by using a new optimization algorithm to constrain parameter signs with prior knowledge and a perturbation-based ensemble method. <h3>Results</h3> We applied the new inference to long-term species abundance data from the freshwater fish community in the Illinois River, United States. We constructed an ensemble of 668 gLV models that explained 79% of the data on average. The models indicated (at a 70% level of confidence) a strong positive interaction from emerald shiner (<i>Notropis atherinoides</i>) to channel catfish (<i>Ictalurus punctatus</i>), which we could validate using data from a nearby observation site, and predicted that the relative abundances of most fish species will continue to fluctuate temporally and concordantly in the near future. The network shows that the invasive silver carp (<i>Hypophthalmichthys molitrix</i>) has much stronger impacts on native predators than on prey, supporting the notion that the invader perturbs the native food chain by replacing the diets of predators. <h3>Conclusions</h3> Ensemble approaches constrained by prior knowledge can improve inference and produce networks from noisy and sparsely sampled time series data to fill knowledge gaps on real world ecosystems. Such network models could aid efforts to conserve ecosystems such as the Illinois River, which is threatened by the invasion of the silver carp.
Low-Grade Albuminuria and Incidence of Cardiovascular Disease Events in Nonhypertensive and Nondiabetic Individuals
Authors: Johan Ärnlöv, Jane C. Evans, James B. Meigs, Thomas J. Wang, Caroline S. Fox, Daniel Levy, Emelia J. Benjamin, Ralph B. D’Agostino, Ramachandran S. Vasan
Journal: Circulation (2005)

Background— Data are limited with regard to the relations of low-grade albuminuria (below the microalbuminuria threshold) and incidence of cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals. Methods and Results— We examined the association of urinary albumin excretion (spot urine albumin indexed to creatinine [UACR]) and the incidence of CVD events and all-cause mortality in 1568 nonhypertensive, nondiabetic Framingham Offspring Study participants (mean age, 55 years; 58% women) free of CVD. On follow-up (median, 6 years), 54 participants (20 women) developed a first CVD event, and 49 (19 women) died. After adjustment for established risk factors, increasing UACR was associated with greater risk of CVD (hazards ratio [HR] per SD increment in log UACR, 1.36; 95% CI, 1.00 to 1.87) and death (HR per SD increment in log UACR, 1.55; 95% CI, 1.10 to 2.20). Participants with UACR greater than or equal to the sex-specific median (≥3.9 μg/mg for men, ≥7.5 μg/mg for women) experienced a nearly 3-fold risk of CVD (adjusted HR, 2.92; 95% CI, 1.57 to 5.44; P &lt;0.001) and a borderline significantly increased risk of death (adjusted HR, 1.75; 95% CI, 0.95 to 3.22; P =0.08) compared with those with UACR below the median. The increased CVD risk associated with UACR at or above the median remained robust in analyses restricted to individuals without microalbuminuria (n=1470) and in subgroups with intermediate (n=1469) and low (n=1186) pretest probabilities of CVD. Conclusions— In our community-based sample of middle-aged nonhypertensive, nondiabetic individuals, low levels of urinary albumin excretion well below the current microalbuminuria threshold predicted the development of CVD. Our observations add to the growing body of evidence that challenges the notion that UACR &lt;30 μg/mg indicates “normal” albumin excretion.
Smoking cessation may improve the microbial flora profile
Authors: S J Mehta
Journal: Thorax (2007)

▴ Brook I, Gober AE. Effect of smoking cessation on the microbial flora. Arch Otolaryngol Head Neck Surg. 2007;133:135–8.

[OpenUrl][1][CrossRef][2][PubMed][3]



The nasopharyngeal flora of smokers contains more potential pathogens and fewer bacteria with interfering capability than those of non-smokers. This paper studied the effect of smoking cessation on levels of these organisms. Two nasopharyngeal swabs were taken from 20 adults who had smoked at least 10 cigarettes a day for …

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Flexible Sigmoidoscopy in the PLCO Cancer Screening Trial: Results From the Baseline Screening Examination of a Randomized Trial
Authors: Joel L. Weissfeld, Robert E. Schoen, Paul F. Pinsky, Robert S. Bresalier, Timothy Church, Susan Yurgalevitch, Joseph H. Austin, Philip C. Prorok, John K. Gohagan
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial is a randomized clinical trial to test the effectiveness of cancer screening, including the effect of flexible sigmoidoscopy screening on colorectal cancer mortality. Here we report findings from the baseline screening flexible sigmoidoscopy examination. Methods: Analyses included 77 465 men and women aged 55–74 years who were enrolled at 10 screening centers. The trial administered baseline risk factor questionnaires, offered 60-cm flexible sigmoidoscopy examinations, referred patients with screen-detected colorectal polyps or masses to personal physicians, and tracked subjects with polyps or masses to determine results from diagnostic follow-up. Cochran–Mantel–Haenszel statistics and logistic regression were used to test for differences in proportions according to sex and age. Results: A total of 64 658 subjects (83.5%) underwent screening flexible sigmoidoscopy, and at least one polyp or mass was identified in 15 150 subjects (23.4%). Of these, 74.2% received follow-up lower endoscopic procedures. Follow-up lower endoscopy was more frequent in subjects with at least one larger (≥0.5 cm) polyp or mass (86.0% [95% confidence interval {CI} = 84.6% to 87.4%] and 81.0% [95% CI = 79.8% to 82.2%] in women and men, respectively) than in those with a smaller (<0.5 cm) polyp or mass (69.1% [95% CI = 67.5% to 70.6%] and 65.4% [95% CI = 64.1% to 66.7%] in women and men, respectively). The yields per 1000 screened, depending on 5-year age group, were as follows: for colorectal cancer, 1.1–2.5 in women and 2.4–5.6 in men; for advanced adenoma, 18.0–30.4 in women and 36.1–49.1 in men; and for colorectal cancer or any adenoma, 50.6–79.6 in women and 101.9–128.6 in men. Approximately 77% (130/169) of the colorectal adenocarcinoma patients were stage I or II at diagnosis. Conclusions: Acceptance of screening flexible sigmoidoscopy was high. Diagnostic follow-up varied according to polyp size, yet cancer or adenoma detection rates met expectations.
Radioiodinated versus Radiometal-Labeled Anti–Carcinoembryonic Antigen Single-Chain Fv-Fc Antibody Fragments: Optimal Pharmacokinetics for Therapy
Authors: Vania Kenanova, Tove Olafsen, Lawrence E. Williams, Nora H. Ruel, Jeffrey Longmate, Paul J. Yazaki, John E. Shively, David Colcher, Andrew A. Raubitschek, Anna M. Wu
Journal: Cancer Research (2007)

Abstract Antibody fragments with optimized pharmacokinetic profiles hold potential for detection and therapy of tumor malignancies. We studied the behavior of three anti–carcinoembryonic antigen (CEA) single-chain Fv-Fc (scFv-Fc) variants (I253A, H310A, and H310A/H435Q; Kabat numbering system) that exhibited differential serum persistence. Biodistribution studies done on CEA-positive tumor xenografted mice revealed that the 111In-labeled I253A fragment with the slowest clearance kinetics (T1/2β, 27.7 h) achieved the highest tumor uptake (44.6% ID/g at 24 h), whereas the radiometal-labeled H310A/H435Q fragment with the most rapid elimination (T1/2β, 7.05 h) reached a maximum of 28.0% ID/g at 12 h postinjection. The H310A protein was characterized by both intermediate serum half-life and tumor uptake. The 111In-based biodistribution studies showed that all three fragments were eliminated primarily through the liver, and hepatic radiometal activity correlated with the rate of fragment clearance. The 111In-labeled H310A/H435Q protein exhibited the highest liver uptake (23.5% ID/g at 24 h). Metabolism of the 125I-labeled scFv-Fc proteins resulted in low normal organ activity. Finally, the 125I/111In biodistribution data allowed for dose estimations, which suggest the 131I-labeled scFv-Fc H310A/H435Q as a promising candidate for radioimmunotherapy. [Cancer Res 2007;67(2):718–26]
Somatic PKD2 Mutations in Individual Kidney and Liver Cysts Support a “Two-Hit” Model of Cystogenesis in Type 2 Autosomal Dominant Polycystic Kidney Disease
Authors: YORK PEI, TERRY WATNICK, NING HE, KAIRONG WANG, YAN LIANG, PATRICK PARFREY, GREGORY GERMINO, PETER ST. GEORGE-HYSLOP
Journal: Journal of the American Society of Nephrology (1999)

Abstract. An intriguing feature of autosomal dominant polycystic kidney disease (ADPKD) is the focal and sporadic formation of renal and extrarenal cysts. Recent documentation of somatic PKD1 mutations in cystic epithelia of patients with germ-line PKD1 mutations suggests a “two-hit” model for cystogenesis in type 1 ADPKD. This study tests whether the same mechanism for cystogenesis might also occur in type 2 ADPKD. Genomic DNA was obtained from 54 kidney and liver cysts from three patients with known germ-line PKD2 mutations, using procedures that minimize contamination of cells from noncystic tissue. Using intragenic and microsatellite markers, these cyst samples were screened for loss of heterozygosity. The same samples were also screened for somatic mutations in five of the 15 exons in PKD2 by single-stranded conformational polymorphism analysis. Loss of heterozygosity was found in five cysts, and unique intragenic mutations were found in seven other cysts. In 11 of these 12 cysts, it was also determined that the somatic mutation occurred nonrandomly in the copy of PKD2 inherited from the unaffected parent. These findings support the “two-hit” model as a unified mechanism for cystogenesis in ADPKD. In this model, the requirement of a somatic mutation as the rate-limiting step for individual cyst formation has potential therapeutic implications.
Recommendations and Considerations Related to Preparticipation Screening for Cardiovascular Abnormalities in Competitive Athletes: 2007 Update
Authors: Barry J. Maron, Paul D. Thompson, Michael J. Ackerman, Gary Balady, Stuart Berger, David Cohen, Robert Dimeff, Pamela S. Douglas, David W. Glover, Adolph M. Hutter, Michael D. Krauss, Martin S. Maron, Matthew J. Mitten, William O. Roberts, James C. Puffer
Journal: Circulation (2007)
Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial
Authors: Roy S Herbst, Rafat Ansari, Frederique Bustin, Patrick Flynn, Lowell Hart, Gregory A Otterson, Gordana Vlahovic, Chang-Heok Soh, Paula O'Connor, John Hainsworth
Journal: The Lancet (2011)
Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study
Authors: Ka Sing Wong, Christopher Chen, Ping Wing Ng, Tak Hong Tsoi, Ho Lun Li, Wing Chi Fong, Jonas Yeung, Chi Keung Wong, Kin Keung Yip, Hong Gao, Hwee Bee Wong
Journal: The Lancet Neurology (2007)

Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD.Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0.4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80-300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493).Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index >or=85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI -5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0-1 (odds ratio 1.55, 95% CI 1.02-2.35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78%vs 79% and 73%vs 75%, respectively).Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.
Quantifying GPIIb/IIIa Receptor Binding Using 2 Monoclonal Antibodies
Authors: Martin Quinn, Adele Deering, Maura Stewart, Dermot Cox, Brendan Foley, Desmond Fitzgerald
Journal: Circulation (1999)

Background —Dosing of glycoprotein (GP) IIb/IIIa receptor antagonists is frequently based on the inhibition of platelet aggregation, which may be influenced by the agonist used or concurrent medications. Here we describe a monoclonal antibody-based technique to quantify total and ligand-occupied GPIIb/IIIa receptors. Methods and Results —In vitro binding of monoclonal antibodies, LYP18 (Mab1) and 4F8 (Mab2), to the GPIIb/IIIa complex, was characterized using purified receptor and to platelets by flow cytometry. Patients undergoing coronary angioplasty received a single 20 mg dose of the oral GPIIb/IIIa antagonist, xemilofiban, or matching placebo, and antibody binding was compared with inhibition of platelet aggregation. Mab1 and Mab2 were bound to purified GPIIb/IIIa and to unoccupied, inactivated receptor on platelets. Mab2 identified the β3 subunit, whereas Mab1 was complex-specific. Neither antibody interfered with the other’s binding, suggesting that they identified distinct sites. Mab1 identified 53 300±5423 GPIIb/IIIa sites per platelet, whereas Mab2 identified 50 120±5066 sites per platelet. Mab1 binding was inhibited by abciximab in a dose dependent manner (IC 50 , 0.85±0.1 μg/mL), whereas Mab2 binding was unaffected. In contrast, the 2 small molecular weight antagonists, SC-57101A (IC 50 , 0.22±0.06 μmol/L) and eptifibatide (IC 50 , 0.35±0.14 μmol/L) inhibited Mab2 but not Mab1 binding. In patients treated with xemilofiban, Mab1 binding was unaltered but Mab2 binding decreased from 37 930±2061 sites per platelet at baseline to 8318±870 sites per platelet 6 hours after dosing ( P &lt;0.0001). Platelet aggregation to adenosine diphosphate (20 μmol/L) fell to 3±3% of baseline in line with the inhibition of Mab2 binding (correlation coefficient 0.8, P &lt;0.0001). Conclusions —Mab1 and Mab2 bind to GPIIb/IIIa and are differentially displaced by abciximab and small molecular weight antagonists. These antibodies may be used to monitor receptor number and occupancy during administration of a GPIIb/IIIa antagonist.