tbuckley/cabot-search huggingface dataset:
Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients
Authors: Karsten Wursthorn, Mechthild Jung, Antonio Riva, Zachary D. Goodman, Patricia Lopez, Weibin Bao, Michael P. Manns, Heiner Wedemeyer, Nikolai V. Naoumov
Journal: Hepatology (2010)

The impact of prolonged direct antiviral therapy on hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B is poorly understood. We quantitatively assessed serum HBsAg levels during 3 years of telbivudine treatment, as well as their relationship with virologic and biochemical characteristics in 162 hepatitis B e antigen–positive patients who maintained undetectable serum hepatitis B virus (HBV) DNA long-term. Telbivudine treatment progressively reduced serum HBsAg levels (mean ± SD) from baseline (3.8 ± 0.6 log10 IU/mL) to treatment week 24 (3.4 ± 0.7 log10 IU/mL), treatment year 1 (3.3 ± 0.8 log10 IU/mL), and treatment year 3 (3.0 ± 1.4 log10 IU/mL) ( P &lt;0.0001). In this patient population, HBsAg loss was observed in nine (6%) of 162 patients through year 3. During the first year of treatment, three patterns of HBsAg decline were observed: rapid (≥1 log10 IU/mL) in 32 patients, slow (0-1 log10 IU/mL) in 74 patients, and steady levels in 56 patients. These findings were associated with different likelihoods of HBsAg loss during long-term telbivudine therapy. Eight of 32 patients with rapid HBsAg decline versus none of 56 patients with steady HBsAg levels achieved HBsAg loss at year 3 ( P = 0.0024). HBV genotype was a significant determinant for HBsAg kinetics, with the fastest decline in genotype A patients. In patients with subsequent HBsAg loss, viral antigens were already undetectable in liver biopsy samples after 1 year of treatment. This was associated with markedly enhanced antiviral T cell reactivity. Conclusion: In patients who have effective suppression of viral replication during telbivudine treatment, a rapid decline in serum HBsAg levels during the first year may identify those with a greater likelihood of achieving HBsAg clearance. (Hepatology 2010
Interaction of Diphenylhydantoin (Phenytoin) and Phenobarbital with Hormonal Mediation of Fetal Rat Bone Resorption In Vitro
Authors: Theodore J. Hahn, Cheryl R. Scharp, Catherine A. Richardson, Linda R. Halstead, Arnold J. Kahn, Steven L. Teitelbaum
Journal: Journal of Clinical Investigation (1978)

Chronic administration of high doses of anticonvulsant drugs frequently produces classic osteomalacia with bone histologic changes characteristic of increased parathyroid hormone (PTH) effect in man. However, several reports have documented defects in calcified tissue metabolism suggestive of an end-organ resistance to PTH after chronic anticonvulsant drug therapy. To examine the direct action of anticonvulsant drugs on bone resorption, we investigated the effects of diphenylhydantoin (phenytoin) (DPH) (100-200 mug/ml) and phenobarbital (10-400 mug/ml) on basal and hormonally mediated resorption 5-day cultures of fetal rat forelimb rudiments. In this system both drugs significantly inhibited basal and PTH-stimulated (45)Ca and [(3)H]hydroxyproline release, as well as 1,25-dihydroxyvitamin D(3)-stimulated (45)Ca release. The effects of DPH and phenobarbital were additive, with DPH exhibiting a several-fold more potent inhibitory effect than phenobarbital. Whereas DPH exhibited a striking synergism with the inhibitory effects of human calcitonin (HCT) on PTH-induced resorption, the effect of phenobarbital was merely additive to that of HCT. PTH and PTH plus HCT-induced increases in bone cyclic AMP (cAMP) content were significantly inhibited by DPH but not by phenobarbital. However, in contrast to effects on (45)Ca release, DPH inhibition of cAMP generation was not accentuated in the presence of HCT. It is concluded that: (a) both DPH and phenobarbital can directly inhibit basal and hormonally stimulated bone resorption, with DPH being much more potent in this regard; (b) DPH appears to inhibit bone resorption via a cAMP-independent mechanism and has an additional suppressive effect on PTH-induced cAMP generation; and (c) the synergistic interaction of DPH and HCT in inhibiting (45)Ca release occurs at a site independent of cAMP generation.
What are the consequences of deployment to Iraq and Afghanistan on the mental health of the UK armed forces? A cohort study
Authors: Nicola T Fear, Margaret Jones, Dominic Murphy, Lisa Hull, Amy C Iversen, Bolaji Coker, Louise Machell, Josefin Sundin, Charlotte Woodhead, Norman Jones, Neil Greenberg, Sabine Landau, Christopher Dandeker, Roberto J Rona, Matthew Hotopf, Simon Wessely
Journal: The Lancet (2010)
IgE levels in cord blood and at 4–5 days of age: relation to clinical symptoms of atopic disease up to 18 months of age
Authors: G. Lilja, S. G. O. Johansson, E. Kusoffsky, H. ÖMman
Journal: Allergy (1990)

To evaluate the variation in sertim IgE levels during the neonatal period and its relation to the development of atopy, 83 infants with a heredity of atopy were studied with regard to the concentration of IgE in cord blood (CB) and capillary blood on the fourth or fifth day of life. During the neonatal period, the average IgE level remained unchanged in the whole group but there were large individual changes. Among 22 infants with CB‐IgE levels 0.9 kU/l the IgE concentrations in 50% decreased below this value on days 4–5. The correlation between maternal IgE and CB‐IgE concentrations (r s =0.41; P &lt;0.001) was interpreted as indicating a probable contamination with maternal blood. This view was supported by the presence of an elevated IgA level and of IgE antibodies against inhalant allergens in 16% of the cord blood samples of which 69% had an IgE level exceeding 0.9 kU/l. It therefore seems preferable to collect the blood samples on the fourth or fifth day. However, in the 74 infants available for atopic classification at 18 months of age, the positive predictive value of IgE determinations was low: on days 4–5 25–38% and in CB 42%. A high CB‐IgE level may merely be an indication of the mother's atopic state.
Identifying Individuals at High Risk of Melanoma: A Practical Predictor of Absolute Risk
Authors: Thomas R. Fears, DuPont Guerry, Ruth M. Pfeiffer, Richard W. Sagebiel, David E. Elder, Allan Halpern, Elizabeth A. Holly, Patricia Hartge, Margaret A. Tucker
Journal: Journal of Clinical Oncology (2006)

Purpose We developed a model to estimate the 5-year absolute risk of melanoma to efficiently identify individuals at increased risk of melanoma for potential interventions. Patients and Methods We used data from a case-control study with 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia, PA and San Francisco, CA; matched controls were 945 patients from outpatient clinics with similar catchment areas. All participants underwent extensive interviews and skin examinations. We selected easily obtained clinical characteristics and responses to simple questions for study in order to develop sex-specific relative risk models. These models were combined with incidence and mortality rates by United States geographic areas to develop estimates of the absolute risk of developing melanoma within 5 years. Results Relative risk models yielded an attributable risk of 86% for men and 89% for women, using at most seven variables. Attributable risks did not vary by age, ultraviolet B flux or hours outdoors. The absolute individual risks varied widely, depending on age, other host characteristics, and geographic area. Individual absolute risk can be estimated using a program available online. Conclusion Our procedures allow for estimating the absolute risk of developing melanoma to assist in the identification of patients at high risk. Such high-risk individuals could undergo interventions including a complete skin examination, counseling to avoid sun exposures, regular self and professional surveillance, or participation in prevention trials. It is important to emphasize that these projections are not intended to identify current melanoma cases.
Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
Authors: Xiaozhou Fan, Sergio A. Quezada, Manuel A. Sepulveda, Padmanee Sharma, James P. Allison
Journal: The Journal of Experimental Medicine (2014)

Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade with a monoclonal antibody yields durable responses in a subset of cancer patients and has been approved by the FDA as a standard therapy for late-stage melanoma. We recently identified inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade and ICOS engagement by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong support for the development of combinatorial therapies incorporating anti–CTLA-4 and ICOS engagement.
The effects of acetylcholine on the electrical activity of canine cardiac Purkinje fibers.
Authors: D C Gadsby, A L Wit, P F Cranefield
Journal: Circulation Research (1978)

We studied the effects of acetylcholine (ACh) on small bundles of canine cardiac Purkinje fibers exposed to normal, or low-chloride (isethionate) Tyrode's solution in a rapid superfusion system. In superfusate containing 4 mM K+, the resting potential of Purkinje fibers may be either "low," near -40 mV, or "high," near -90 mV. ACh, at 10(-6) to 10 (-5) M, increased the membrane potential from both the low and high resting levels and, in low-Cl solution, often induced a maintained shift in potential from the low to the high level. The increase in membrane potential caused by ACh was greater at the low than at the high level. ACh, at 10(-6) to 10(-5) M, reduced action potential duration in both normal and low-Cl Tyrode's solution, the effect being more marked in the latter. These effects of ACh were reversibly abolished by atropine (5 X 10(-5) M), indicating that they were mediated via muscarinic ACh receptors, and they probably result from an increase in membrane K+ conductance since 10(-5) M ACh reversibly reduced, by 13% on the average, the amplitudes of the steady changes in membrane potential evoked by applying small current pulses (-5 to -25 nA, 200 msec). ACh (10(-5) M) also diminished the rate of, or stopped, spontaneous activity arising from either level of membrane potential. The cessation of spontaneous slow response activity, arising from the low level, sometimes was accompanied by a maintained shift of the membrane potential to the high resting level. It is concluded that the action of ACh on Purkinje fibers is qualitatively similar to its action on sinoatrial nodal and atrial cells.
Preparation of bronchoalveolar lavage fluid with microscope slide smears
Authors: AB Thompson, H Teschler, YM Wang, N Konietzko, U Costabel
Journal: European Respiratory Journal (1996)

The method of preparation of bronchoalveolar lavage fluid (BALF) for cytological examination can significantly affect the results of cellular quantitation. Investigations have shown that cytocentrifugation leads to an underestimation of the number of lymphocytes and membrane filter preparation to an underestimation of the number of neutrophils. As a simple alternative to these two techniques, BALF cells could be prepared by the microscope slide smear technique, which is familiar as the means for preparing peripheral blood for differential counts. In order to compare cell differentials determined by microscope slide technique with differentials resulting from cytocentrifugation, cells were isolated from 35 BALF samples using standard methods, and counted using a haematocytometer. Forty thousand cells in 200 microL were prepared by cytocentrifugation (3 min, 57 x g; Cytospin 2) and 5 x 10(5) cells in 5 microL by microscope slide smear. Both samples were air-dried, stained using May-Grünwald Giemsa stain, and 600 cells were counted to obtain differentials. To test the adequacy of sampling by the microscope slide smear technique, known quantities of lymphocytes or neutrophils were added to fixed numbers of BALF cells, microscope slide smears prepared, and differentials determined on 600 cells. The resulting differentials were compared to the calculated differentials. Preparation of BALF cells with the microscope slide smear technique yielded well-preserved cell morphology. Compared to cytocentrifugation, microscope slide smear preparations had significantly higher percentages of lymphocytes. The microscope slide smears for the samples with predetermined numbers of cells yielded lymphocyte and neutrophil percentages which did not differ from the calculated differentials (59.6 +/- 1.5 vs 59.6 +/- 5.2% and 54.6 +/- 6.0 vs 53.1 +/- 6.0%, respectively). Varying the number of cells counted from 100 to 800 confirmed the reproducibility of the counts for counting 600 cells. Using 5 x 10(5), 2.5 x 10(5), or 1 x 10(5) cells per preparation demonstrated that adequate specimens could be obtained from as few as 1 x 10(5) cells. Thus, microscope slide smear preparation is a simple and accurate method for the quantitation of bronchoalveolar lavage fluid cytology.
Thiotepa-Based High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Patients With Recurrent or Progressive CNS Germ Cell Tumors
Authors: Shakeel Modak, Sharon Gardner, Ira J. Dunkel, Casilda Balmaceda, Marc K. Rosenblum, Douglas C. Miller, Steven Halpern, Jonathan L. Finlay
Journal: Journal of Clinical Oncology (2004)

To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs).Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR.Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P <.001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC.Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.
Genome-wide association study of prostate cancer identifies a second risk locus at 8q24
Authors: Meredith Yeager, Nick Orr, Richard B Hayes, Kevin B Jacobs, Peter Kraft, Sholom Wacholder, Mark J Minichiello, Paul Fearnhead, Kai Yu, Nilanjan Chatterjee, Zhaoming Wang, Robert Welch, Brian J Staats, Eugenia E Calle, Heather Spencer Feigelson, Michael J Thun, Carmen Rodriguez, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Fredrick R Schumacher, Edward Giovannucci, Walter C Willett, Geraldine Cancel-Tassin, Olivier Cussenot, Antoine Valeri, Gerald L Andriole, Edward P Gelmann, Margaret Tucker, Daniela S Gerhard, Joseph F Fraumeni, Robert Hoover, David J Hunter, Stephen J Chanock, Gilles Thomas
Journal: Nature Genetics (2007)
Coagulation Cascade Activation Causes CC Chemokine Receptor-2 Gene Expression and Mononuclear Cell Activation in Hemodialysis Patients
Authors: Giovanni Pertosa, Simona Simone, Michela Soccio, Daniela Marrone, Loreto Gesualdo, Francesco Paolo Schena, Giuseppe Grandaliano
Journal: Journal of the American Society of Nephrology (2005)

Priming of the coagulation cascade during hemodialysis (HD) leads to the release of activated factor X (FXa). The binding of FXa to its specific receptors, effector protease receptor-1 (EPR-1) and protease-activated receptor-2 (PAR-2), may induce the activation of peripheral blood mononuclear cells (PBMC) and promote a chronic inflammatory state that is responsible for several HD-related morbidities. In the attempt to elucidate the mechanisms underlying the coagulation-associated inflammation in HD, 10 HD patients were randomized to be treated subsequently with a cellulose acetate membrane (CA) and Ethylen-vinyl-alcohol (EVAL), a synthetic membrane that has been shown to reduce FXa generation. At the end of each experimental period, surface FXa and thrombin receptors (EPR-1 and PAR-1, -2, and -4) and CCR2 (monocyte chemoattractant protein-1 receptor) gene expression in isolated PBMC were examined. the ability of dialytic membranes to activate protein-tyrosine kinases and the stress-activated kinase JNK and to modulate the generation of terminal complement complex (TCC) was also investigated. EPR-1 and PAR-2 and -4 mRNA expression, barely detectable in normal PBMC, were significantly upregulated in HD patients, particularly in those who were treated with CA. A striking increase of tyrosine-phosphorylated proteins and JNK activation was observed at the end of HD only in CA-treated patients. Simultaneously, an increased gene expression for both splicing isoforms of CCR2, A and B, only in PBMC from CA-treated patients was demonstrated. The increased CCR-2 mRNA abundance was followed by a significant increase in its protein synthesis. The high expression of CCR2 was associated with an increased generation of plasma TCC and a significant drop in leukocyte and monocyte count. By contrast, EVAL treatment slightly lowered TCC generation and normalized leukocyte count. In vitro FXa induced CCR2 A and B expression and JNK activation in freshly isolated PBMC. FXa-induced CCR2 mRNA expression was completely abolished by JNK and tyrosine kinase inhibition. In conclusion, these data suggest that subclinical clotting activation may cause an increased CCR2 gene and protein expression on uremic PBMC, contributing to HD-related chronic microinflammation. The use of the less coagulation-activating membrane, EVAL, may reduce PBMC activation through the modulation of the stress-activated kinase JNK.
Prospective Study of Air Pollution and Bronchitic Symptoms in Children with Asthma
Authors: Rob McConnell, Kiros Berhane, Frank Gilliland, Jassy Molitor, Duncan Thomas, Fred Lurmann, Edward Avol, W. James Gauderman, John M. Peters
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The relationship of bronchitic symptoms to ambient particulate matter and to particulate elemental and organic carbon (OC), nitrogen dioxide (NO2), and other gaseous pollutants was examined in a cohort of children with asthma in 12 Southern California communities. Symptoms, assessed yearly by questionnaire from 1996 to 1999, were associated with the yearly variability of particulate matter with aerodynamic diameter less than 2.5 microg (odds ratio [OR] 1.09/microg/m3; 95% confidence interval [CI] 1.01-1.17), OC (OR 1.41/microg/m3; 95% CI 1.12-1.78), NO2 (OR 1.07/ppb; 95% CI 1.02-1.13), and ozone (OR 1.06/ppb; 95% CI 1.00-1.12). The ORs associated with yearly within-community variability in air pollution were larger than the effect of the between-community 4-year average concentrations. In two pollutant models, the effects of yearly variation in OC and NO2 were only modestly reduced by adjusting for other pollutants, except in a model containing both OC and NO2; the effects of all other pollutants were reduced after adjusting for OC or NO2. We conclude that OC and NO2 deserve greater attention as potential causes of the chronic symptoms of bronchitis in children with asthma and that previous cross-sectional studies may have underestimated the risks associated with air pollution.
Economic Impact of Case-Mix Adjusting the Dialysis Composite Rate
Authors: Richard A. Hirth, Erik C. Roys, John R.C. Wheeler, Joseph M. Messana, Marc N. Turenne, Rajiv Saran, Alyssa S. Pozniak, Robert A. Wolfe
Journal: Journal of the American Society of Nephrology (2005)

The Medicare program reimburses dialysis providers a flat rate for a bundle of services that comprise the basic dialysis treatment. This payment system is being modified to incorporate case-mix adjustment for age and body size, which have been shown to influence dialysis costs. This study simulated the economic impact of the recently issued Medicare rule on case-mix adjustment by estimating the variation in payments across patients, facilities, and broad classes of facilities. Case-mix adjustment results in considerable patient-level variation in payments (dollar 12.99 SD in case-mix adjusted payments). The variation across dialysis facilities is smaller but still economically significant (dollar 3.77 SD). However, there was little evidence that particular classes of facilities (e.g., ownership, chain membership, size) will be substantially advantaged or disadvantaged by case-mix adjustment. There do seem to be modest changes in the regional distribution of payments.
Pitfalls and Recommendations in Cases of Laser Removal of Decorative Tattoos With Pigmented Lesions
Authors: Laura Pohl, Kathrine Kaiser, Christian Raulin
Journal: JAMA Dermatology (2013)

<h3>Importance</h3> Pigmented lesions in decorative tattoos cause diagnostic difficulties at a clinical and dermoscopic level. In cases of laser removal of tattoos, hidden suspicious nevi may be revealed gradually. <h3>Observations</h3> We describe the first case of a malignant melanoma that developed on a preexisting nevus within a tattoo during and between the phases of laser removal. The patient refused to undergo excision of the nevus until we made excision conditional for continued laser treatment. <h3>Conclusions and Relevance</h3> The English literature reports 16 cases of malignant melanoma developing in tattoos. Correlation between the placement of tattoos and the development of malignant melanoma remains unclear. Our case emphasizes the diagnostic problems of pigmented lesions within tattoos. For safety reasons, tattoos should never be placed on pigmented lesions; if they are, the tattoos should not undergo laser treatment. We suggest an excision before starting laser tattoo removal. Dermoscopic assessments on a regular basis during the period of tattoo removal are recommended.
Medicare Part D: Ongoing Challenges for Doctors and Patients
Authors: Gretchen Jacobson, Gerard Anderson
Journal: Annual Review of Medicine (2010)

The Medicare Modernization Act was intended to improve access to prescription drugs for millions of seniors, by providing a range of benefit packages with different prices and different formularies for beneficiaries to choose from. The major challenge for physicians has been to recognize when a Medicare beneficiary has coverage versus when that patient is in the "doughnut hole" where Medicare beneficiaries do not have coverage and therefore have to pay the full cost of the drugs out-of-pocket. A second challenge is that different Medicare beneficiaries are enrolled in different drug plans, and drugs that are covered in some plans are not covered in other plans.