tbuckley/cabot-search huggingface dataset:
Predictive Pharmacokinetic-Pharmacodynamic Modeling of Tumor Growth Kinetics in Xenograft Models after Administration of Anticancer Agents
Authors: Monica Simeoni, Paolo Magni, Cristiano Cammia, Giuseppe De Nicolao, Valter Croci, Enrico Pesenti, Massimiliano Germani, Italo Poggesi, Maurizio Rocchetti
Journal: Cancer Research (2004)

The available mathematical models describing tumor growth and the effect of anticancer treatments on tumors in animals are of limited use within the drug industry. A simple and effective model would allow applying quantitative thinking to the preclinical development of oncology drugs. In this article, a minimal pharmacokinetic-pharmacodynamic model is presented, based on a system of ordinary differential equations that link the dosing regimen of a compound to the tumor growth in animal models. The growth of tumors in nontreated animals is described by an exponential growth followed by a linear growth. In treated animals, the tumor growth rate is decreased by a factor proportional to both drug concentration and number of proliferating tumor cells. A transit compartmental system is used to model the process of cell death, which occurs at later times. The parameters of the pharmacodynamic model are related to the growth characteristics of the tumor, to the drug potency, and to the kinetics of the tumor cell death. Therefore, such parameters can be used for ranking compounds based on their potency and for evaluating potential differences in the tumor cell death process. The model was extensively tested on discovery candidates and known anticancer drugs. It fitted well the experimental data, providing reliable parameter estimates. On the basis of the parameters estimated in a first experiment, the model successfully predicted the response of tumors exposed to drugs given at different dose levels and/or schedules. It is, thus, possible to use the model prospectively, optimizing the design of new experiments.
Pro-Active Call Center Treatment Support (PACCTS) to Improve Glucose Control in Type 2 Diabetes
Authors: Robert J. Young, Jean Taylor, Tim Friede, Sally Hollis, James M. Mason, Pauline Lee, Edna Burns, Andrew F. Long, Tina Gambling, John P. New, J. Martin Gibson
Journal: Diabetes Care (2005)

OBJECTIVE— To determine whether Pro-Active Call Center Treatment Support (PACCTS), using trained nonmedical telephonists supported by specially designed software and a diabetes nurse, can effectively improve glycemic control in type 2 diabetes. RESEARCH DESIGN AND METHODS— A randomized controlled implementation trial of 1-year duration was conducted in Salford, U.K. The trial comprised 591 randomly selected individuals with type 2 diabetes. By random allocation, 197 individuals were assigned to the usual care (control) group and 394 to the PACCTS (intervention) group. Lifestyle advice and drug treatment in both groups followed local guidelines. PACCTS patients were telephoned according to a protocol with the frequency of calls proportional to the last HbA1c level. The primary outcome was absolute reduction in HbA1c, and the secondary outcome was the proportion of patients reducing HbA1c by at least 1%. RESULTS— A total of 332 patients (84%) in the PACCTS group and 176 patients (89%) in the control group completed the study. Final HbA1c values were available in 374 patients (95%) in the PACCTS group and 180 patients (92%) in the usual care group. Compared with usual care, HbA1c improved by 0.31% (95% CI 0.11–0.52, P = 0.003) overall in the PACCTS patients. For patients with baseline HbA1c &amp;gt;7%, the improvement increased to 0.49% (0.21–0.77, P &amp;lt; 0.001), whereas in patients with baseline HbA1c &amp;lt;7% there was no change. The difference in the proportions of patients achieving a ≥1% reduction in HbA1c significantly favored the PACCTS intervention: 10% (4–16, P &amp;lt; 0.001) overall and 15% (7–24, P &amp;lt; 0.001) for patients with baseline HbA1c &amp;gt;7%. CONCLUSIONS— In an urban Caucasian trial population with blood glucose HbA1c &amp;gt;7%, PACCTS facilitated significant improvement in glycemic control. Further research should extend the validity of findings to rural communities and other ethnic groups, as well as to smoking and lipid and blood pressure control.
The Natural History and Epidemiology of Diabetic Nephropathy
Authors: Joseph V. Selby
Journal: JAMA (1990)

PERSONS with diabetes are at increased risk for several types of kidney disease,<sup>1</sup>but the predominant cause of end-stage renal disease (ESRD) in this disorder is diabetic nephropathy—a complication unique to diabetes. Since the initiation of Medicare coverage for treatment of ESRD in 1972, the proportion of new ESRD cases attributed to diabetic nephropathy has increased from approximately 10% in 1973<sup>2</sup>to 30% in 1987.<sup>3</sup>Diabetes is now the single most frequent reason for beginning treatment of ESRD, with 10 025 new cases caused by diabetic nephropathy in 1987.<sup>3</sup> In this article, we review the natural history and epidemiology of diabetic nephropathy and the evidence for efficacy of preventive and therapeutic measures. From this review, a strategy for preventing and controlling this important cause of morbidity is outlined. <h3>NATURAL HISTORY OF DIABETIC KIDNEY DISEASE</h3> <i>Diabetic nephropathy</i>is currently defined by the presence of a persistently positive
Subacute lupus erythematosus-like eruption due to terbinafine: report of three cases
Authors: V.A. Hill, J. Chow, N. Cowley, R.A. Marsden
Journal: British Journal of Dermatology (2003)

Three female patients presented with a severe subacute lupus erythematosus (LE)‐like eruption due to terbinafine prescribed for suspected onychomycosis (Fig. 1). Two patients had serological evidence of autoimmune disease predisposing to photosensitivity. One patient, who had used a sunbed the day before the eruption appeared had a low titre positive speckled ANA, borderline anti‐RO antibodies, and raised anti‐RNP antibodies. The other had a positive anti‐SS‐A antibody. The third patient had neutropenia. Antihistone antibodies were negative. Histology in two cases was consistent with subacute LE. All three patients had strikingly similar eruptions that took several weeks to resolve, requiring treatment with topical clobetasol propionate and oral prednisolone. Cutaneous adverse reactions to terbinafine are usually mild, the most common being urticaria and erythema multiforme.1 There are previous reports of terbinafine induced photosensitivity, cutaneous LE‐like reactions2, 3 and erythema multiforme in patients with autoimmune disease,4 which may be a risk factor.
Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group
Authors: Norbert Schmitz, Lorenz Trümper, Marita Ziepert, Maike Nickelsen, Anthony D. Ho, Bernd Metzner, Norma Peter, Markus Loeffler, Andreas Rosenwald, Michael Pfreundschuh
Journal: Blood (2010)
Prognosis and Management of Patients With Node-Negative Invasive Breast Carcinoma That Is 1 cm or Smaller in Size (stage 1; T1a,bN0M0): A Review of the Literature
Authors: Emer O. Hanrahan, Vicente Valero, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2006)

Mammographic screening has led to an increase in the number of small, node-negative breast cancers being diagnosed. Node-negative breast cancers that are < or = 1 cm are stage T1a,bN0M0. Controversy surrounds the prognosis of these patients with locoregional therapy only and the need for adjuvant systemic therapy.We performed a comprehensive review of the literature describing outcome and prognostic factors in stage T1a,bN0M0 breast cancer. We also reviewed current guidelines for systemic therapy in these patients.Early studies reported 10-year relapse-free survival (RFS) rates higher than 90% without adjuvant systemic therapy, but some more recent data suggest inferior outcomes. High tumor grade is the most consistent factor associated with poor prognosis. Other adverse prognostic factors are younger age, lymphovascular invasion (LVI), high Ki-67, and larger tumors within the T1a,b subgroup. Patients with high-grade tumors and/or LVI may have 10-year RFS rates of less than 75% in the absence of systemic therapy. The prognostic significance of hormone receptor status is unclear. Current guidelines for the systemic management of early-stage breast cancer differ when applied to stage T1a,bN0M0, reflecting the controversial nature of the issue.Adjuvant systemic therapy is advisable for most patients with stage T1a,bN0M0 breast cancer who have grade 3 tumors and/or LVI. Other T1a,bN0M0 cases should be considered for systemic therapy based on clinicopathologic factors with known prognostic significance and assessment of the risk-benefit ratio. More reliable tools are needed to assess the prognosis of patients with stage T1a,bN0M0 breast cancer and their potential to benefit from specific therapeutic agents.
Importance of Continuous Chest Compressions During Cardiopulmonary Resuscitation
Authors: Karl B. Kern, Ronald W. Hilwig, Robert A. Berg, Arthur B. Sanders, Gordon A. Ewy
Journal: Circulation (2002)

Background — Interruptions to chest compression–generated blood flow during cardiopulmonary resuscitation (CPR) are detrimental. Data show that such interruptions for mouth-to-mouth ventilation require a period of “rebuilding” of coronary perfusion pressure to obtain the level achieved before the interruption. Whether such hemodynamic compromise from pausing to ventilate is enough to affect outcome is unknown. Methods and Results — Thirty swine (weight 35±2 kg) underwent 3 minutes of untreated ventricular fibrillation before 12 minutes of basic life support CPR. Animals were randomized to receive either standard airway (A), breathing (B), and compression (C) CPR with expired-gas ventilation in a 15:2 compression-to-ventilation ratio or continuous chest compression CPR. Those randomized to the standard 15:2 group had no chest compressions for a period of 16 seconds each time the 2 ventilations were delivered. Defibrillation was attempted at 15 minutes of cardiac arrest. All resuscitated animals were supported in an intensive care environment for 1 hour, then in a maintenance facility for 24 hours. The primary end point of neurologically normal 24-hour survival was significantly better in the experimental group receiving continuous chest compression CPR (12 of 15 versus 2 of 15; P &lt;0.0001). Conclusions — Mouth-to-mouth ventilation performed by single layperson rescuers produces substantial interruptions in chest compression–supported circulation. Continuous chest compression CPR produces greater neurologically normal 24-hour survival than standard ABC CPR when performed in a clinically realistic fashion. Any technique that minimizes lengthy interruptions of chest compressions during the first 10 to 15 minutes of basic life support should be given serious consideration in future efforts to improve outcome results from cardiac arrest.
Hazards of long distance cycling
Authors: A K Midgley
Journal: BMJ (1989)

<h3>Objectives</h3> In 2012, the WHO estimated that 6 million new cases of syphilis per year would occur worldwide, including 937 000 in Brazil. Early diagnosis and treatment of syphilis are essential to reduce morbidity and prevent transmission. The availability of rapid tests (RTs) for this diagnosis means that testing can be performed more quickly, as a point-of-care test, even in non-laboratory environments and requires only simple technical training to antibodies detection. The objective of this study was to evaluate the performance and operational aspects of seven commercially available RTs for syphilis in Brazil. <h3>Methods</h3> Seven rapid treponemal tests were evaluated for sensitivity, specificity, accuracy and Kappa value, according to a panel composed of 493 members. The operational performance of the assay was also determined for these tests. <h3>Results</h3> The seven RTs showed sensitivity ranging from 94.5% to 100% when compared with the reference tests and specificity of between 91.5% and 100%. All the RTs evaluated presented good operational performance, and only one failed to present the minimum specificity as defined by Brazil’s Ministry of Health. <h3>Conclusion</h3> All the tests presented good operational performance, and the professionals who performed them considered them to be easy to use and interpret. This evaluation is important for making informed choices of tests to be used in the Brazilian Unified Health System.
Abstract 4108: Syndecan-1 overexpression enhances colon cancer growth by modulating heparan sulfate binding growth factors sensitivity
Authors: Hiroaki Hayashi, Kazuhisa Minamiguchi, Akira Kanoh, Keisuke Ishida, Tadashi Terada, Kenichi Matsuo
Journal: Cancer Research (2010)

Abstract Syndecan-1 is a multifaceted transmembrane heparan sulfate proteoglycan known for its significant role in a wide range of cellular processes by interacting with a multitude of extracellular components. Although loss of syndecan-1 correlates well with the gain of cancerous characteristics in a wide range of cancers, increased expression of syndecan-1 also corresponds to adverse outcomes in some cancers. The biological function is yet to be completely understood in most of malignancies, including colon cancer. In the present study, to evaluate biological functions of syndecan-1, its expression level was altered, and subsequent outcomes were examined using human colon cancer LoVo cells. Ectopic expression of syndecan-1 in LoVo cells (LoVo/SDC1) led to larger tumor formation than did control LoVo cells (LoVo/mock) in mice. Lower concentrations of HB-EGF and HGF could activate their receptors in LoVo/SDC1 than in LoVo/mock. And, the prolonged phosphorylation of EGFR induced by HB-EGF was observed in LoVo/SDC1. Furthermore, HB-EGF more effectively promoted cell growth of LoVo/SDC1 than that of LoVo/mock. Blockade of syndecan-1 using small-interfering RNA (siRNA) gene knockdown canceled sensitization of LoVo/SDC1 to HB-EGF and diminished LoVo/SDC1 cell growth stimulated by HB-EGF. These results suggest that syndecan-1 overexpression may contribute to heparan sulfate binding growth factors sensitization and their promoting effects to cancer growth. Finally, we examined the effects of syndecan-1 on chemotherapy in the presence of heparan sulfate binding growth factors. In comparison to LoVo/mock, LoVo/SDC1 was resistant to some cytotoxic drugs (paclitaxel, 5-FU, or CPT-11) in the presence of HB-EGF or HGF. Blockade of syndecan-1 using siRNA diminished chemotherapy resistance of LoVo/SDC1 caused by HB-EGF. These findings demonstrate that syndecan-1 confers chemotherapy resistance in colon cancer through concomitant heparan sulfate binding growth factors sensitization. In summary, our results identify syndecan-1 as a functional coreceptor for heparan sulfate binding growth factors that activate their receptors and promote their downstream pathway in colon cancer cells. Syndecan-1 overexpression may contribute to tumor growth and the chemotherapy resistance characteristic of colon cancer. Therefore, therapeutic invention aimed at inhibiting this molecule may be useful in cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4108.
Remuneration of Soviet medical personnel.
Authors: M Ryan
Journal: BMJ (1987)

At the start of 1987, in the continuing economy wide attack on endemic bureaucratic incompetence, the Politburo issued a public rebuke to senior officials of the health service. Most prominent among them was S PBurenkov, health minister of the Soviet Union, who chose to take early retirement as the evident alternative to dismissal. The stated reason why the bell tolled for Burenkov was that he personally, together with the ministry's supervisory board (Kollegiya), had displayed  irresponsible attitude towards the implementation of an important social measure. Passed on 16 October last year, this measure required the phased introduction of substantial salary increases for the various categories of personnel employed in health care and the social welfare services. Although the initial round of increases were due to take effect from 1 November, in most regions of the country including the city of Moscow they started to be paid only during the second half of December and then thanks to intervention by high authority ?namely, the party's Central Committee and the Council of Ministers.1 That these bodies were monitoring progress of the measure so closely can be accounted a fascinating sign of fast changing times and the decision to mete out swift and public retribution for the ministry's lethargy may well be thought to bear the authentic imprint of Mikhail Gorbachov himself.
Ito–Cell Gene Expression and Collagen Regulation
Authors: Francis R. Weiner, Marie-Adele Giambrone, Mark J. Czaja, Anish Shah, Giorgio Annoni, Shizuko Takahashi, Mahboubeh Eghbali, Mark A. Zern
Journal: Hepatology (1990)

Ito cells are perisinusoidal cells thought to be a major source of collagen in normal and fibrotic livers. These cells appear to have features similar to several cell types but when cultured assume a fibroblast–like morphology. In this study we evaluated the phenotype of both freshly isolated and cultured Ito cells by examining their gene expression. To better define the modulators of Ito–cell collagen synthesis, we also examined the effect of transforming growth factor–β1, tumor necrosis factor–α and dexamethasone on collagen synthesis by these cells. Northern hybridization analysis revealed that cultured Ito cells expressed different types of procollagen mRNAs than did freshly isolated cells. Cultured cells contained large amounts of type I procollagen mRNA and lesser amounts of types III and IV, whereas freshly isolated cells contained more type IV procollagen mRNA than types I and III. Treatment of cultured cells with either transforming growth factor–β1 or tumor necrosis factor–α resulted in a greater than threefold increase in total collagen content, and the effects of these cytokines on Ito–cell collagen synthesis involved different levels of gene regulation. Transforming growth factor–β1–treated cells had an approximately threefold increase in their type I procollagen mRNA levels, whereas no increase in this mRNA level was found in tumor necrosis factor–α–treated cells. Transforming growth factor–β1 treatment induced a twofold increase in transforming growth factor–β1 mRNA content in cultured cells. In contrast to transforming growth factor–β1, dexamethasone inhibited type I procollagen and transforming growth factor–β1 mRNA content by at least twofold in cultured cells. These results suggest that cultured Ito cells alter their collagen gene expression such that they become phenotypically more fibroblast–like. Furthermore, transforming growth factor–β1's induction of its own mRNA in Ito cells suggests that these cells are capable of amplifying their collagen synthesis. Finally, the inhibition of transforming growth factor–β1 and procollagen type I gene expression by dexamethasone suggests another way steroids may be beneficial in the treatment of certain forms of chronic liver disease.
Pigeon Breeders' Disease
Authors: JORDAN N. FINK
Journal: Annals of Internal Medicine (1968)

The clinical and laboratory features of 12 patients with pigeon breeders' disease were studied during symptomatic and asymptomatic phases. The results indicated that this hypersensitivity pneumonitis may occur as an acute, subacute, or chronic form differing in type and intensity of signs, symptoms, and response to therapy. Pulmonary function tests in most symptomatic breeders revealed restriction, obstruction, or a diffusion defect. More than one half of the breeders had chest X-ray findings suggestive of a diffuse interstitial process with secondary alveolar involvement. Lung biopsy showed a granulomatous interstitial pneumonitis and, in the one case of the chronic form, an obstructive bronchiolitis. An Arthus type of skin reactivity to challenge with pigeon antigens was found in all patients. Sera from all 12 breeders contained precipitating antibody against various pigeon antigens. Our experience indicates that the preferential therapy for these patients is avoidance of contact with pigeons.
No spitting, no smoking
Authors: R. Smith
Journal: BMJ (2003)

able to make true informed choices, support and funding for routine mammography will continue to be questioned. Evidence based interventions can prevent fractures in elderly peopleFractures among elderly people represent an important and preventable public health problem.In a clinical review on the topic, Woolf and Akesson (p 89) state that prevention of fractures involves reducing falls, minimising the morbidity associated with falls, and maximising bone strength at all ages.Pharmacological treatment is most cost effective for people at high risk: women, people over 75 years old, and elderly patients with osteoporosis or previous falls.Frailty and comorbidity are also associated with risk of fractures.The authors outline a selective case finding approach to help clinicians recognise and treat elderly patients at risk.
Inferring Natural Selection on Fine-Scale Chromatin Organization in Yeast
Authors: G. A. Babbitt, Y. Kim
Journal: Molecular Biology and Evolution (2008)

Despite its potential role in the evolution of complex phenotypes, the detection of negative (purifying) and positive selection on noncoding regulatory sequence has been elusive because of the inherent difficulty in predicting the functional consequences of mutations on noncoding sequence. Because the functioning of regulatory sequence depends upon both chromatin configuration and cis-regulatory factor binding, we investigate the idea that the functional conservation of regulatory regions should be associated with the conservation of sequence-dependent bending properties of DNA that determine its affinity for the nucleosome. Recent advances in the computational prediction of sequence-dependent affinity to nucleosomes provide an opportunity to distinguish between neutral and nonneutral evolution of fine-scale chromatin organization. Here, a statistical test is presented for detecting evolutionary conservation and/or adaptive evolution of nucleosome affinity from interspecies comparisons of DNA sequences. Local nucleosome affinities of homologous sequences were calculated using 2 recently published methods. A randomization test was applied to sites of mutation to evaluate the similarity of DNA–nucleosome affinity between several closely related species of Saccharomyces yeast. For most of the genes we analyzed, the conservation of local nucleosome affinity was detected at a few distinct locations in the upstream noncoding region. Our results also demonstrate that different patterns of chromatin evolution have shaped DNA–nucleosome interaction at the core promoters of TATA-containing and TATA-less genes and that elevated purifying selection has maintained low affinity for nucleosome in the core promoters of the latter group. Across the entire yeast genome, DNA–nucleosome interaction was also discovered to be significantly more conserved in TATA-less genes compared with TATA-containing genes.