tbuckley/cabot-search huggingface dataset:
Seroprevalence of human herpesvirus type 8 infection in patients with lung carcinoma
Authors: Shih-Ming Tsao, Chun-Liang Lai, Ming Nan Lin, Cheng-Chuan Su
Journal: European Respiratory Journal (2012)

Background : Human herpesvirus type 8 (HHV-8) DNA is found consistently in all types of Kaposi's sarcoma (KS), which is sometimes seen in human immunodeficiency virus (HIV) non-infected patients with immunologic abnormalities. Lung carcinoma is one of the most common malignancies developing in immunocompromised patients. However, the prevalence of HHV-8 infection in lung carcinoma patients is unclear. Methods : Blood samples were collected from 109 lung carcinoma patients with malignant pleural effusion and 109 age-matched healthy controls and analyzed for lymphocyte and monocyte counts, and presence of HHV-8 antibody and DNA. All study subjects were negative for anti-HIV antibodies. Results : Lung carcinoma patients had significantly lower mean lymphocyte counts and significantly higher monocyte counts than the healthy controls ( P < 0.001). Three patients with lymphopenia and stage IV tumor were positive for HHV-8 DNA , one of them was negative for HHV-8 antibody. HHV-8 positivity was significantly higher in patients (42.2%), particularly in male patients (50.8%), than in healthy controls (24.8%) ( P = 0.006 and < 0.001, respectively). HHV-8 positivity was significantly greater in male patients (50.8%) than in female patients (29.5%) ( P = 0.028), and in patients with stage IV tumors somewhat greater than with stage III B tumors ( P = 0.416). HHV-8 antibody titers in patients also significantly exceeded those in healthy controls ( P = 0.004). All subjects positive for HHV-8 were not associated with clinical manifestations of HHV-8 infection. Conclusions : HHV-8 seroprevalence was significantly greater in lung carcinoma patients than in healthy controls, and associated with gender.
Present and future therapies of hepatitis B: From discovery to cure
Authors: T. Jake Liang, Timothy M. Block, Brian J. McMahon, Marc G. Ghany, Stephan Urban, Ju‐Tao Guo, Stephen Locarnini, Fabien Zoulim, Kyong‐Mi Chang, Anna S. Lok
Journal: Hepatology (2015)

Hepatitis B virus (HBV) is a significant global pathogen, infecting more than 240 million people worldwide. While treatment for HBV has improved, HBV patients often require lifelong therapies and cure is still a challenging goal. Recent advances in technologies and pharmaceutical sciences have heralded a new horizon of innovative therapeutic approaches that are bringing us closer to the possibility of a functional cure of chronic HBV infection. In this article, we review the current state of science in HBV therapy and highlight new and exciting therapeutic strategies spurred by recent scientific advances. Some of these therapies have already entered into clinical phase, and we will likely see more of them moving along the development pipeline.With growing interest in developing and efforts to develop more effective therapies for HBV, the challenging goal of a cure may be well within reach in the near future.
Evidence for the clonal abortion theory of B-lymphocyte tolerance.
Authors: G J Nossal, B L Pike
Journal: The Journal of Experimental Medicine (1975)

This paper deals with the behavior of adult mouse bone marrow cells placed in tissue culture with or without antigen, and subsequently assessed for immune competence after adoptive transfer into lethally X-irradiated, syngeneic hosts. Attention was focussed on B lymphocytes through using hapten human gamma globulin (HGG) preparations as putative tolerogens in tissue culture, the T-cell-independent antigens DNP-POL and NIP-POL as challenge injections in adoptive hosts, and numbers of hapten-specific PFC in host spleens for the quantitation of immune competence. It was found that the capacity of bone marrow cells to mount an adoptive immune response rose by a factor of about fivefold over 3 days in tissue culture. This rise was completely abolished by the presence in the culture of hapten-HGG conjugates with about one mole of hapten per carrier molecule. The prevention of the emergence of immune competence amongst maturing B cells was termed clonal abortion tolerogenesis. Dose-response studies showed the lowest effective antigen concentration to be between 2.5 times 10- minus 10 and 2.5 times 10- minus 9 M, and a standard concentration of 2.5 times 10- minus 8 M was chosen as producing near maximal effects. The tolerance was antigen-specific and time-dependent, being maximal only when antigen was present continuously as the cultured cells was maturing. It did not depend on the presence of T lymphocytes in marrow, and was not of an "infectious" type. In contrast to tolerogenesis of mature B lymphocytes by high antigen concentrations, it could not be abolished by lipopolysaccharide. We speculate that clonal abortion may be a tolerance mechanism of great physiological significance for self-recognition, and discuss the results in the framework of other recent tolerance models, including those involving receptor blockade and suppressor T cells.
Extent of surgical resection of high-grade glioma among the elderly
Authors: J. H. Badhiwala, S. A. Almenawer
Journal: Neuro-Oncology (2015)

Zou et al express 2 concerns in their letter about our recent meta-analysis.1 First, they believe that some included articles may have used biopsy for diagnostic purposes and accordingly should not be pooled in the analyses. Their doubt that biopsy might have been used for diagnosis is the exact definition we used (“the use of surgical procedures exclusively for pathological diagnostic purposes”) in the meta-analysis and study protocol.1 Researchers2,3 compare biopsy to resection for 2 main reasons: (i) biopsy cannot be achieved without resecting a minimal amount of tumor tissue and (ii) by examining biopsy as a control group versus patients undergoing resection, the value of extent of surgical resection can be defined. The second concern by Zou et al is that outcomes among elderly persons with high-grade gliomas (HGGs) depend on multiple factors, which is a reiteration of what we discussed in our study. It is almost impossible in a meta-analysis and extremely difficult in a randomized trial to account for similar characteristics between examined groups related to patients’ age, gender, and underlying comorbidities, tumor size; location, histology, and genetics; preoperative functional status, type, dose, and duration of chemotherapy; and type, dose, and duration of radiotherapy. Our main goal was to examine the value of extent of surgical resection, not to recommend gross total resection for all patients. Hence, our conclusion that improved outcomes were associated with higher extent of resection was confounded by what we reported in the abstract and manuscript “if considered in conjunction with known established safety measures when managing elderly patients harboring HGGs.”1 We deliberately and precisely used “associated” in describing the relation between improved outcomes and increasing extent of surgical resection.1 This implies that extent of resection is a significant factor—not, however, the only factor. A recommendation of gross total resection for all patients cannot be made and accordingly was avoided in our systematic review. Not resecting HGGs at the expense of safety and functional outcomes among the elderly is a well-known established practice by neurosurgeons globally. The main question we aimed to answer through the first meta-analysis of the literature and a large cohort among the elderly was about selecting the optimal extent of resection when all extents can be achieved within the safety limits. This should not be interpreted in isolation of the other well-known factors.
H pylori colocalises with MUC5AC in the human stomach
Authors: G R Van den Brink
Journal: Gut (2000)

The bacterium Helicobacter pylori is able to adhere to and to colonise the human gastric epithelium, yet the primary gene product responsible as a receptor for its adherence has not been identified.To investigate the expression of the gastric mucins MUC5AC and MUC6 in the gastric epithelium in relation to H pylori colonisation in order to examine their possible roles in the binding of H pylori.Seventy two consecutive patients suspected of having H pylori infection.MUC5AC, MUC6, and H pylori were detected in single sections of antral biopsy specimens using immunohistochemical triple staining.MUC5AC was expressed in the superficial epithelium and the upper part of the gastric pits. MUC6 expression was detected in the lower part of the gastric pits. The expression of both mucins in the epithelium was complementary. In each patient, there was a sharply delineated transition between MUC5AC and MUC6 producing cell populations. In all H pylori positive patients there was a striking colocalization of H pylori and MUC5AC; more than 99% of the bacteria were associated with either extracellular MUC5AC or the apical domain of MUC5AC producing cells.H pylori is very closely associated with extracellular MUC5AC and epithelial cells that produce MUC5AC. This indicates that MUC5AC, but not MUC6, plays a role in the adhesion of H pylori to the gastric mucosa.
Phase III Comparison of Twice-Daily Split-Course Irradiation Versus Once-Daily Irradiation for Patients With Limited Stage Small-Cell Lung Carcinoma
Authors: James A. Bonner, Jeff A. Sloan, Thomas G. Shanahan, Burke J. Brooks, Randolph S. Marks, James E. Krook, James B. Gerstner, Andrew Maksymiuk, Ralph Levitt, James A. Mailliard, Henry D. Tazelaar, Shauna Hillman, James R. Jett
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Because small-cell lung cancer is a rapidly proliferating tumor, it was hypothesized that it may be more responsive to thoracic irradiation (TI) given twice-daily than once-daily. This hypothesis was tested in a phase III trial. PATIENTS AND METHODS: Patients with limited-stage small-cell lung cancer were entered onto a phase III trial, and all patients initially received three cycles of etoposide (130 mg/m 2 × 3) and cisplatin (30 mg/m 2 × 3). Subsequently, patients who did not have progression to a distant site (other than brain) were randomized to twice-daily thoracic irradiation (TDTI) versus once-daily thoracic irradiation (ODTI) given concomitantly with two additional cycles of etoposide (100 mg/m 2 × 3) and cisplatin (30 mg/m 2 × 3). The irradiation doses were TDTI, 48 Gy in 32 fractions, with a 2.5-week break after the initial 24 Gy, and ODTI, 50.4 Gy in 28 fractions. After thoracic irradiation, the patients received a sixth cycle of etoposide/cisplatin, followed by prophylactic cranial irradiation (30 Gy/15 fractions) if they had a complete response. RESULTS: Of 311 assessable patients enrolled in the trial, 262 underwent randomization to TDTI or ODTI. There were no differences between the two treatments with respect to local-only progression rates, overall progression rates, or overall survival. The patients who received TDTI had greater esophagitis (≥ grade 3) than those who received ODTI (12.3% v 5.3%; P = .05). Although patients received thoracic irradiation encompassing the postchemotherapy volumes, only seven of 90 local failures were out of the portal of irradiation. CONCLUSION: When TI is delayed until the fourth cycle of chemotherapy, TDTI does not result in improvement in local control or survival compared with ODTI.
A randomized trial comparing single and double chest tube application after pulmonary lobectomy
Authors: Makoto Tanaka, Motoyasu Sagawa, Yuichiro Machida, Masakatsu Ueno, Nozomu Motono, Katsuo Usuda, Tsutomu Sakuma
Journal: European Respiratory Journal (2013)

Objectives: In order to expand residual lungs appropriately after pulmonary lobectomy, two chest tubes have been usually placed in the thoracic cavity. Although only one chest tube has recently been placed, it was unclear whether one chest tube was sufficient for the postoperative management of patients, especially those who underwent VATS lobectomy. Therefore, we carried out a randomized controlled trial to compare postoperative drainage using one chest tube with that using two chest tubes after pulmonary lobectomy, including VATS lobectomy. Methods: Patients who underwent lobectomies with mediastinal nodal dissection in our hospital were randomly assigned to two groups: one chest tube group and two chest tubes group. Number of cases requiring thoracentesis (indicating inadequate expansion of residual lung), total amount of drainage fluid, duration of drainage, analgesia requirements and pain score were compared between two groups. Results: From January 2009 to March 2012, a total of 108 patients were registered. There were no statistically significant differences in age, gender, pathological stage or histological type of the patients between the two groups. There were no patients who needed thoracentesis. There were no significant differences in the number of cases with pleurodesis, amount/duration of drainage and the magnitude of pain between the two groups. Conclusions: Since the difference in the number of chest tubes did not affect the expansion of residual lung, the amount/duration of drainage or postoperative pain in patients who underwent pulmonary lobectomy, one chest tube is sufficient for post-lobectomy chest drainage, even after VATS lobectomy.
Interleukin-4 Receptor α Signaling in Myeloid Cells Controls Collagen Fibril Assembly in Skin Repair
Authors: Johanna A. Knipper, Sebastian Willenborg, Jürgen Brinckmann, Wilhelm Bloch, Tobias Maaß, Raimund Wagener, Thomas Krieg, Tara Sutherland, Ariel Munitz, Marc E. Rothenberg, Anja Niehoff, Rebecca Richardson, Matthias Hammerschmidt, Judith E. Allen, Sabine A. Eming
Journal: Immunity (2015)
Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial.
Authors: L D Kaplan, J O Kahn, S Crowe, D Northfelt, P Neville, H Grossberg, D I Abrams, J Tracey, J Mills, P A Volberding
Journal: Journal of Clinical Oncology (1991)

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.
Early Diagnosis and Surgical Management of Acoustic Neuroma: Is it Cost Effective?
Authors: D A Moffat, D G Hardy
Journal: Journal of the Royal Society of Medicine (1989)

Audiological and radiological advances and refinement of microsurgical techniques have facilitated the diagnosis and excision of very small acoustic nerve tumours with a low morbidity and mortality. Is this cost effective? In an attempt to answer this question, an analysis of 66 cases of surgically treated acoustic neuromas is presented. This represents a part of a series of otoneurosurgical procedures carried out at Addenbrooke's Hospital over the last five years. By studying the relative morbidity of early and late surgical intervention in these cases, and by costing the exercise, the justification for early diagnosis and treatment is presented both in financial and human terms.
Comparison of budesonide and fluticasone propionate on COPD macrophage phagocytosis and killing of bacteria
Authors: Kylie Belchamber, Amy Turner, Rebecca Holloway, Peter Barnes, Louise Donnelly
Journal: European Respiratory Journal (2014)

Inhaled glucocorticosteroids (ICS) are associated with an increased rate of pneumonia in COPD. The mechanism underlying this is unknown. However, recent data suggest that this is more prevalent in patients treated with fluticasone propionate (FP) than budesonide (BUD). Macrophages and monocyte-derived macrophages (MDM) from COPD patients are deficient in clearing bacteria and this might explain increased bacterial colonisation in COPD. It is possible that ICS could further suppress this response, therefore we examined the effect of BUD and FP on MDM phagocytosis and killing of  Haemophilus influenzae  (HI) and  Streptococcus pneumoniae  (SP).  MDM from COPD patients (n=3-12) were pre-incubated with BUD or FP for 30 min after which phagocytosis of fluorescently labelled inert beads, or heat killed HI or SP, after 1 and 4 h were measured fluorimetrically. For bacterial killing, MDM were pre-incubated with BUD or FP prior to culture with HI or SP for 4 h, antibiotics were added and cells lysed and plated on agar plates. After 12 h, colonies were counted.  Neither BUD nor FP altered MDM phagocytosis of beads or SP at any time point (n=10-12). FP (10 -5 M) suppressed phagocytosis of HI by ∼20% (p -9 M-10 -7 M suppressed phagocytosis by ∼10% (p  These data suggest that macrophages may respond differently to FP compared to BUD with respect to phagocytosis of bacteria and may explain why FP is more likely than BUD to be associated with pneumonia in COPD patients.
Vascular Endothelial Growth Factor 189 mRNA Isoform Expression Specifically Correlates With Tumor Angiogenesis, Patient Survival, and Postoperative Relapse in Non–Small-Cell Lung Cancer
Authors: Ang Yuan, Chong-Jen Yu, Sow-Hsong Kuo, Wen-Jone Chen, Fang-Yue Lin, Kwen-Tay Luh, Pan-Chyr Yang, Yung-Chie Lee
Journal: Journal of Clinical Oncology (2001)

The purpose of this study was to evaluate the correlation between the expression of four different vascular endothelial growth factor (VEGF) mRNA isoforms (VEGF121, VEGF165, VEGF 189, and VEGF206) and the clinicopathologic characteristics, tumor angiogenesis, and outcome of patients with non-small-cell lung cancer.We examined the expression of four different VEGF mRNA isoforms in 57 non-small-cell lung cancers using reverse transcriptase polymerase chain reaction and the tumor angiogenesis using immunohistochemical staining.All 57 lung cancer samples expressed the VEGF121, VEGF165, and VEGF189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tumoral VEGF189 mRNA isoform expression ratio was associated with a high intratumoral microvessel count (P = .013), short survival (< 24 months; P = .001), and early postoperative relapse (< 12 months; P = .001). Survival and postoperative relapse time were significantly shorter in patients with a high compared with a low tumor VEGF189 mRNA isoform expression ratio (P = .0001 and P = .0086, respectively, log-rank test). In contrast, the VEGF165 and VEGF 206 mRNA isoform expression ratios showed no statistical correlation with tumor angiogenesis, postoperative relapse time, or survival. A high VEGF121 mRNA isoform expression ratio was associated with short survival (< 24 months) and early relapse (< 12 months). Multivariate analysis showed that VEGF 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and postoperation recurrence.The VEGF189 mRNA isoform expression ratio shows a greater correlation with tumor angiogenesis, postoperative relapse time, and survival than do the expression ratios for the VEGF121, VEGF165, and VEGF206 mRNA isoforms and can be used as a prognostic indicator for patients with non-small-cell lung cancers.
Serum surfactant protein D may predict the effect of pirfenidone in idiopathic pulmonary fibrosis
Authors: Kimiyuki Ikeda, Masanori Shiratori, Keiki Yokoo, Mitsuo Ohtsuka, Hirofumi Chiba, Hiroki Takahashi
Journal: European Respiratory Journal (2013)

Background;  Pirfenidone (PFD), a new drug with anti-fibrotic effect, was approved for the treatment of idiopathic pulmonary fibrosis (IPF) in Japan in 2008. In prior clinical trials, this drug showed a clinical effect decelerating the progression of restrictive respiratory disturbance, particularly in patients with higher vital capacity (%VC>70%) at baseline. Previous study showed surfactant protein D (SP-D), a serum marker of IPF, predicts the annual decrease of VC (ΔVC/y) and the prognosis in the natural course of IPF. In this study, we investigated whether SP-D could predict the effect of PFD.   Methods;  We enrolled 54 patients with IPF who visited our hospital from 2008 to 2012, fulfilled the criteria of the ATS/ERS/JRS/ALAT statement 2012, to the exclusion of exceptional cases such as familial onset and pleuroparenchymal fibroelastosis. They were divided in PFD-treated group (n=25) and PFD-non-treated group (n=29). Their mean observation period was 25.4 months (13.3-37.4). Distinct three serum markers including SP-D at baseline were analyzed retrospectively in relation to ΔVC/y.   Results;  There was no significant difference between the two groups in patient’s characteristics, serum markers and VC at baseline. SP-D correlated significantly with ΔVC/y in both groups. The inhibitory effect of PFD on ΔVC/y was observed prominently in patients showing not only higher VC (%VC>70%) at baseline but also lower SP-D (under 220 ng/ml). This pharmacological effect was reproduced by evaluation restricted in patients showing higher VC at baseline.   Conclusion;  SP-D and VC at baseline may be independent parameters to predict the effectiveness of PFD in patients with IPF.
Gram-negative prosthetic joint infection treated with debridement, prosthesis retention and antibiotic regimens including a fluoroquinolone
Authors: C.A. Aboltins, M.M. Dowsey, K.L. Buising, T.N. Peel, J.R. Daffy, P.F.M. Choong, P.A. Stanley
Journal: Clinical Microbiology and Infection (2010)