tbuckley/cabot-search huggingface dataset:
Hepatitis B virus DNA, HBeAg and delta infection during the course from acute to chronic hepatitis B virus infection
Authors: Kim Krogsgaard, Jan Aldershvile, Peter Kryger, Poul Andersson, Jens Ole Nielsen, Bengt Göran Hansson
Journal: Hepatology (1985)

The presence of hepatitis B virus DNA in serum was determined in 57 unselected patients during the course from acute to chronic hepatitis B infection. Forty–six (81%) patients were hepatitis B virus DNA–positive in the first available serum sample. Generally, hepatitis B virus DNA was cleared before or at the same time as HBeAg, but in two patients (4%), hepatitis B virus DNA could be demonstrated after HBeAg clearance. One of the latter patients had hepatitis B virus DNA in the presence of anti–HBe. Both patients became hepatitis B virus DNA–negative. Seven of the hepatitis B virus DNA–positive patients received long–term treatment with prednisone, and three of them continued to be hepatitis B virus DNA positive for more than 10 years. Among the untreated patients hepatitis B virus DNA could be detected for up to 7 years, and 10 patients were hepatitis B virus DNA–positive for three years or more. Twenty–four patients (42%) showed serological signs of delta agent infection. Hepatitis B virus DNA clearance was observed in a significantly higher proportion (87%) of delta–infected patients as compared to patients with no delta infection (45%) (p &lt; 0.05). In addition patients with delta infection had a significantly increased hepatitis B virus DNA clearance rate as compared to patients without delta markers in their serum (p &lt; 0.01). In one (8%) delta–infected patient, hepatitis B virus DNA clearance was followed by a fall in transaminases into the normal range as opposed to results in 86% of patients with pure hepatitis B (p &lt; 0.002).
Multicenter Phase I Study of Repeated Intratumoral Delivery of Adenoviral <i>p53</i> in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Toshiyoshi Fujiwara, Noriaki Tanaka, Susumu Kanazawa, Shoichiro Ohtani, Yasuo Saijo, Toshihiro Nukiwa, Kunihiko Yoshimura, Tetsuo Sato, Yoshikatsu Eto, Sunil Chada, Haruhiko Nakamura, Harubumi Kato
Journal: Journal of Clinical Oncology (2006)

To determine the feasibility, safety, humoral immune response, and biologic activity of multiple intratumoral injections of Ad5CMV-p53, and to characterize the pharmacokinetics of Ad5CMV-p53 in patients with advanced non-small-cell lung cancer (NSCLC).Fifteen patients with histologically confirmed NSCLC and p53 mutations were enrolled onto this phase I trial. Nine patients received escalating dose levels of Ad5CMV-p53 (1 x 10(9) to 1 x 10(11) plaque-forming units) as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with Ad5CMV-p53 in combination with intravenous administration of cisplatin (80 mg/m2). Patients were monitored for toxicity, vector distribution, antibody formation, and tumor response.Fifteen patients received a total of 63 intratumoral injections of Ad5CMV-p53 without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues throughout the period of treatment despite of the presence of neutralizing antiadenovirus antibody. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting at least 9 months, and two patients had progressive disease.Multiple courses of intratumoral Ad5CMV-p53 injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit.
High Nuclear S100A6 (Calcyclin) Is Significantly Associated with Poor Survival in Pancreatic Cancer Patients
Authors: Dale Vimalachandran, William Greenhalf, Christopher Thompson, Jutta Lüttges, Wendy Prime, Fiona Campbell, Andrew Dodson, Richard Watson, Tatjana Crnogorac-Jurcevic, Nicholas Lemoine, John Neoptolemos, Eithne Costello
Journal: Cancer Research (2005)

Abstract Recent studies have reported elevated levels of S100A6 in pancreatic ductal adenocarcinoma cells. Here, we describe a detailed analysis of S100A6 expression in benign (n = 32), malignant (n = 60), and premalignant pancreatic ductal cells [96 pancreatic intraepithelial neoplasias (PanIN) from 46 patients]. S100A6 staining was more intense in malignant cells than in benign cells (P = 0.0001). In malignant cells, staining was higher in the nucleus than in the cytoplasm (P = 0.003). Univariate analysis revealed a significant decrease in survival time for patients with high levels of nuclear (P = 0.01) but not cytoplasmic (P = 0.20) S100A6. No evidence was found for an association between nuclear S100A6 expression and other variables, including gender, age at surgery, tumor size or grade, nodal metastases, resection margin, vascular invasion, perineural invasion, p53 or Smad4 levels (both linked to survival in previous studies), or the p65 subunit of nuclear factor-κB (a potential regulator of S100A6). Although nodal metastases and resection margin involvement were also associated with poor survival (P = 0.06 in both cases), multivariate analysis suggests that nuclear S100A6 is a significant independent indicator of survival (P = 0.003). Whereas PanIN 1a lesions showed a general absence of S100A6 staining, there was a progressive increase in the proportion of positively stained PanINs with increasing PanIN grade. In particular, we observed an increase in the frequency and intensity of nuclear staining. Our results suggest that up-regulation of S100A6 is an early event in pancreatic cancer development and that elevated levels of nuclear S100A6 may affect clinical outcome.
Epidemiology of Asthma Control in Central Italy
Authors: F. Spinozzi, C. Casciari, S. Maio, G. Viegi
Journal: Journal of Allergy and Clinical Immunology (2010)

RATIONALE: Optimal therapeutic asthma control may be influenced by several mechanisms. We focused on co-existing rhinitis and adherence to international guidelines (GINA) to analyze the relevance of other known worsening factors. METHODS: An observational epidemiologic survey was conducted in an ambulatory setting of general practitioners and allergy/pulmonologists in Umbria Region (Central Italy) by mean of an asthma control test (ACT) on 267 asthmatic subjects (age range: 6 to 75 years). RESULTS: 83.1% of patients had asthma and rhinitis (n = 222) whereas 16.9% asthma only (n = 45). Clinically moderate and/or severe persistent disease was present in 13.3% of 45 asthmatic subjects and in 24.2% of those with concomitant rhinitis. 6.7% of asthmatics, as compared to 26.4% out of 222 patients with asthma and rhinitis, was never treated (nor continuous, nor as-needed therapy) for their asthmatic symptoms (p = 0.004). Among the latter, 22.2% had moderate and 13.3% severe asthma. All moderate to severe disease patients among the 45 asthmatic-only subjects were treated, according to the GINA guidelines. Exposure to seasonal or perennial allergens, as well as viral infections did not influence asthma control in all studied subjects. ACT score was low (≤ 15) in 11.5% of asthmatic patients and in 23.7% of those with asthma and concomitant rhinitis (p = 0.020). CONCLUSIONS: Asthmatic patients with co-existing rhinitis often display scarce adherence to GINA guidelines, moderate to severe persistent disease and less efficient symptom's control. However, upper respiratory infectious diseases and/or allergen exposure does not seem to further worse their quality of life.
Randomized Phase III Trial of Gefitinib versus Docetaxel in Non–Small Cell Lung Cancer Patients Who Have Previously Received Platinum-Based Chemotherapy
Authors: Dae Ho Lee, Keunchil Park, Joo Hang Kim, Jong-Seok Lee, Sang Won Shin, Jin-Hyoung Kang, Myung-Ju Ahn, Jin Seok Ahn, Cheolwon Suh, Sang-We Kim
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The ISTANA (IRESSA as Second-line Therapy in Advanced NSCLC—KoreA) study compared gefitinib with docetaxel in patients with advanced or metastatic non–small cell lung carcinoma (NSCLC) pretreated with platinum-based chemotherapy. Experimental Design: We conducted a multicenter, randomized, open-label phase III trial of gefitinib (250 mg/d) versus docetaxel (75 mg/m2 day 1 every 3 weeks) in patients with advanced or metastatic NSCLC treated with one previous platinum-based chemotherapy. The primary endpoint was progression-free survival. Results: A total of 161 patients (male, 62%; never smoker, 41%; adenocarcinoma, 68%) were enrolled. Progression-free survival was longer for gefitinib compared with docetaxel (hazard ratio, 0.729; 90% confidence interval, 0.533-0.998; one-sided P = 0.0441). Gefitinib significantly improved objective response rate (28.1% versus 7.6%; two-sided P = 0.0007). In the final analysis of overall survival, the hazard ratio was 0.870 (95% confidence interval, 0.613-1.236; two-sided P = 0.4370). No significant differences were seen in the quality of life or symptom improvement rates between the two treatment groups. Gefitinib was well tolerated, was consistent with previous data and disease, and had fewer serious adverse events and fewer Common Terminology Criteria for Adverse Events grade 3 or 4 adverse events than docetaxel. The incidence of interstitial lung disease–type events was 3.7% (n = 3) with gefitinib and 3.9% (n = 3) with docetaxel. Conclusions: The primary endpoint of progression-free survival was longer with gefitinib than docetaxel, and the secondary endpoints showed superior objective response rate, good tolerability, and similar quality of life improvement rates for gefitinib than docetaxel. Therefore, gefitinib is an important valid treatment option for second-line therapy for Korean NSCLC patients. Clin Cancer Res; 16(4); 1307–14
The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy
Authors: L.C. Hanker, S. Loibl, N. Burchardi, J. Pfisterer, W. Meier, E. Pujade-Lauraine, I. Ray-Coquard, J. Sehouli, P. Harter, A. du Bois
Journal: Annals of Oncology (2012)
<i>Helicobacter pylori</i> gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole
Authors: A E Berstad, J G Hatlebakk, H Maartmann-Moe, A Berstad, P Brandtzaeg
Journal: Gut (1997)

Background — Helicobacter pylori gastritis may spread proximally in the stomach during profound acid inhibition. Aims —To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole. Patients and methods —Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15–73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland. Results —Of these 90 patients, 44 (49%) were found to be infected with H pylori . Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p&lt;0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pylori infected than in the uninfected group and increased further after treatment (p&lt;0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment. Conclusions —A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.
Nelfinavir-induced urticaria and successful desensitization☆☆☆★★★
Authors: Pascal Demoly, Djamel Messaad, Aldo Trylesinski, Vincent Faucherre, Jacqueline Fabre, Jacques Reynes, Christine Delmas, Elisabeth Dohin, Philippe Godard, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (1998)
Fibroblast Growth Factor 2 as a New Approach to Fighting Fear
Authors: Bronwyn M. Graham, Rick Richardson
Journal: JAMA Psychiatry (2015)

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Molecular disruption of RAD50 sensitizes human tumor cells to cisplatin-based chemotherapy
Authors: Waleed M. Abuzeid, Xiaoling Jiang, Guoli Shi, Hui Wang, David Paulson, Koji Araki, David Jungreis, James Carney, Bert W. O’Malley, Daqing Li
Journal: Journal of Clinical Investigation (2009)

Platinum-based drugs that induce DNA damage are commonly used first-line chemotherapy agents for testicular, bladder, head and neck, lung, esophageal, stomach, and ovarian cancers. The inherent resistance of tumors to DNA damage often limits the therapeutic efficacy of these agents, such as cisplatin. An enhanced DNA repair and telomere maintenance response by the Mre11/Rad50/Nbs1 (MRN) complex is critical in driving this chemoresistance. We hypothesized therefore that the targeted impairment of native cellular MRN function could sensitize tumor cells to cisplatin. To test this, we designed what we believe to be a novel dominant-negative adenoviral vector containing a mutant RAD50 gene that significantly downregulated MRN expression and markedly disrupted MRN function in human squamous cell carcinoma cells. A combination of cisplatin and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage and telomere shortening. In cisplatin-resistant human squamous cell cancer xenografts in nude mice, this combination therapy caused dramatic tumor regression with increased apoptosis. Our findings suggest the use of targeted RAD50 disruption as what we believe to be a novel chemosensitizing approach for cancer therapy in the context of chemoresistance. This strategy is potentially applicable to several types of malignant tumors that demonstrate chemoresistance and may positively impact the treatment of these patients.
Use of the Television Monologue with Adolescent Psychiatric Patients
Authors: HARRY A. WILMER
Journal: American Journal of Psychiatry (1970)

Each patient admitted to the youth drug study unit, a therapeutic community for adolescents with drug problems, is asked to make a videotape monologue. The tape is replayed to him immediately, and he can choose to have it erased or to review it with his therapist. The author describes the monologue technique as a unique form of clinical record and revelation about the patient; it also opens new vistas for self-observation.
First-in-Human, Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of RO5126766, a First-in-Class Dual MEK/RAF Inhibitor in Patients with Solid Tumors
Authors: Maria Martinez-Garcia, Udai Banerji, Joan Albanell, Rastilav Bahleda, Saoirse Dolly, Françoise Kraeber-Bodéré, Federico Rojo, Emilie Routier, Ernesto Guarin, Zhi-Xin Xu, Ruediger Rueger, Jean J. L. Tessier, Eliezer Shochat, Steve Blotner, Valerie Meresse Naegelen, Jean-Charles Soria
Journal: Clinical Cancer Research (2012)

Abstract Purpose: This phase I study assessed the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetics, pharmacodynamics, and clinical activity of the first-in-class dual MEK/RAF inhibitor, RO5126766. Experimental Design: Initial dose-escalation was conducted using once daily dosing over 28 consecutive days in 4-week cycles. Further escalation was completed using 2 intermittent dosing schedules [7 days on treatment followed by 7 days off (7on/7off); 4 days on treatment followed by 3 days off (4on/3off)]. Results: Fifty-two patients received RO5126766 at doses of 0.1 to 2.7 mg once daily, 2.7 to 4.0 mg (4 on/3 off), or 2.7 to 5.0 mg (7 on/7 off). The most common DLTs were elevated creatine phosphokinase (CPK) and blurred vision. The MTD for each dosing schedule was 2.25 mg once daily, 4.0 mg (4 on/3 off), and 2.7 mg (7 on/7 off). The dose/schedule recommended for phase II (RP2D) investigation was 2.7 mg (4 on/3 off). Frequent adverse events included rash-related disorders (94.2%), elevated CPK (55.8%), and diarrhea (51.9%). Cmax occurred 1 to 2 hours after dosing and mean terminal half-life was approximately 60 hours. Pharmacodynamic changes included reduced ERK phosphorylation, an increase in apoptosis in tumor tissue, and a reduction in fluorodeoxyglucose (FDG) uptake after 15 days of dosing. Three partial responses were seen: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma. Conclusion: This first-in-human study shows that oral RO5126766 has manageable toxicity, a favorable pharmacokinetic/pharmacodynamic profile, and encouraging preliminary antitumor activity in this population of heavily pretreated patients, achieving tumor shrinkage in around 40% of patients across all dose levels and all tumor types. Clin Cancer Res; 18(17); 4806–19. ©2012 AACR.
Endothelin and vascular function in liver disease
Authors: K Moore
Journal: Gut (2004)

The endothelins are a group of three related peptides with two receptor subtypes, ET(A) and ET(B). Following the discovery of endothelin 1 as a potent vasoconstrictor, there has been intense interest in the role of endothelin on vascular function in liver disease. Speculation on the role of endothelin in the pathogenesis of acute renal failure, including hepatorenal syndrome, has also been speculated.
Implications of Plasma Protein Binding for Pharmacokinetics and Pharmacodynamics of the γ-Secretase Inhibitor RO4929097
Authors: Jianmei Wu, Patricia M. LoRusso, Larry H. Matherly, Jing Li
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Understanding of plasma protein binding will provide mechanistic insights into drug interactions or unusual pharmacokinetic properties. This study investigated RO4929097 binding in plasma and its implications for the pharmacokinetics and pharmacodynamics of this compound. Experimental Design: RO4929097 binding to plasma proteins was determined using a validated equilibrium dialysis method. Pharmacokinetics of total and unbound RO4929097 was evaluated in eight patients with breast cancer receiving RO4929097 alone and in combination with the Hedgehog inhibitor GDC-0449. The impact of protein binding on RO4929097 pharmacodynamics was assessed using an in vitro Notch cellular assay. Results: RO4929097 was extensively bound in human plasma, with the total binding constant of 1.0 × 106 and 1.8 × 104 L/mol for α1-acid glycoprotein (AAG) and albumin, respectively. GDC-0449 competitively inhibited RO4929097 binding to AAG. In patients, RO4929097 fraction unbound (Fu) exhibited large intra- and interindividual variability; GDC-0449 increased RO4929097 Fu by an average of 3.7-fold. Concomitant GDC-0449 significantly decreased total (but not unbound) RO4929097 exposure. RO4929097 Fu was strongly correlated with the total drug exposure. Binding to AAG abrogated RO4929097 in vitro Notch-inhibitory activity. Conclusions: RO4929097 is highly bound in human plasma with high affinity to AAG. Changes in plasma protein binding caused by concomitant drug (e.g., GDC-0449) or disease states (e.g., ↑AAG level in cancer) can alter total (but not unbound) RO4929097 exposure. Unbound RO4929097 is pharmacologically active. Monitoring of unbound RO4929097 plasma concentration is recommended to avoid misleading conclusions on the basis of the total drug levels. Clin Cancer Res; 18(7); 2066–79. ©2012 AACR.
Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection
Authors: E. Moore, M.B.J. Beadsworth, M. Chaponda, B. Mhango, B. Faragher, J. Njala, H.W.C. Hofland, J. Davies, I.J. Hart, N.J. Beeching, E.E. Zijlstra, J.J. van Oosterhout
Journal: Journal of Infection (2010)
Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study
Authors: Olivier Bruyere, Julien Collette, Manish Kothari, S Zaim, David White, Harry K Genant, Charles Peterfy, Nansa Burlet, Dominique Ethgen, Tim Montague, Christine Dabrowski, Jean-Yves Reginster
Journal: Annals of the Rheumatic Diseases (2006)

To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis.62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging (MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed. A whole organ magnetic resonance imaging score (WORMS) of the knee was calculated for each patient at baseline and at the one year visits. This score consists in a validated, semiquantitative scoring system for whole organ assessment of the knee in osteoarthritis using MRI. Biochemical markers (serum hyaluronic acid, osteocalcin, cartilage glycoprotein 39 (YKL-40), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type I collagen (CTX-I), and urine C-telopeptide of type II collagen (CTX-II)) were measured at baseline and after three months.Baseline markers were not correlated with one year changes observed in cartilage volume and thickness. However, an increase in CTX-II after three months was significantly correlated with a one year decrease in mean thickness of medial tibial and lateral tibial cartilage. Patients in the highest quartile of three month changes in CTX-II experienced a mean loss of 0.07 (0.08) mm of their medial thickness, compared with a mean increase of 0.05 (0.19) mm for patients in the lowest quartile (p = 0.04) Multiple regression analysis showed that high baseline levels of hyaluronic acid are predictive of a worsening in WORMS (p = 0.004).These results suggest that a single measurement of serum hyaluronic acid or short term changes in urine CTX-II could identify patients at greatest risk of progression of osteoarthritis.