tbuckley/cabot-search huggingface dataset:
Successful investigation of household TB contacts in Buriram Hospital during 2011-2012
Authors: Visakha Boontod, Narin Chindavech, Jatuporn Silakaew
Journal: European Respiratory Journal (2014)

Background:  Tuberculosis remains a major public health problem in Thailand. The goal of the National TB Program is to find TB cases and ensure high treatment success rates. Household contacts of TB patients have a high risk of developing tuberculosis. Therefore the search for TB in household contacts is a critical component of an active case finding strategy.   Objective:  To evaluate approaches for screening and diagnosing household contacts of index TB patients in 2011-2012 at Buriram Provincial Hospital   Method:  After identification of an index case in the TB clinic, the TB nurse interviewed the patients on potential household contacts. A one stop service to screen household contacts of index cases was set up and all person who contacted TB were invited for screening. They were interviewed about any symptoms and examination by chest x-ray (AP, Lateral), in children under 15 years old TB skin test was conducted.   Results : Of 283 index cases in 2011, 138 families (48.76%), were screened 464 cases were actively screened and TB was identified in 6 cases (1.29%) who were adults. In 2012, among 359 index TB cases, 84 families were screened (23.39%) with 274 individuals, all of them were actively screened. TB was found in 4 children (1.45%)   Conclusion:  Active screening of household contacts is feasible at the local level and yields a high proportion of cases. This is an important strategy to improve treatment outcomes by early identification and preventing ongoing transmission in the community. The approach does not require massive investment but only taking an active approach to case finding by health care staff in the TB clinic.
Mechanisms of Hypergammaglobulinemia in Pulmonary Sarcoidosis
Authors: Gary W. Hunninghake, Ronald G. Crystal
Journal: Journal of Clinical Investigation (1981)

Pulmonary sarcoidosis is a disorder in which local granuloma formation is perpetuated by activated lung T lymphocytes. The present study suggests that lung T lymphocytes may also play a critical role in modulating local production of antibodies in this disorder. In untreated patients with pulmonary sarcoidosis, the numbers of IgG- and IgM-secreting cells per 103 lung lymphocytes are markedly increased compared with those in normal individuals (P < 0.001 and P < 0.01, respectively); the numbers of IgA-secreting cells in lavage fluid of these patients are not increased (P > 0.2). In contrast to lungs, the numbers of IgG-, IgM-, and IgA-secreting cells in blood of patients with this disorder are similar to those in normal individuals (P > 0.2, each comparison). In patients with pulmonary sarcoidosis, there is a direct correlation between the percentage of bronchoalveolar cells that are T lymphocytes and the percentage of bronchoalveolar cells that secrete IgG (r = 0.79; P < 0.001); in normal individuals there is no such relationship (P > 0.2). When purified sarcoid lung T cells from patients with high proportions of T lymphocytes in their lavage fluid were co-cultured with blood mononuclear cells from normal individuals (without added antigens or mitogens), the B lymphocytes in these normal mononuclear cell suspensions were induced to differentiate into immunoglobulin-secreting cells (P < 0.01). In contrast, blood T lymphocytes from these same patients and lung T lymphocytes from sarcoidosis patients with low proportions of T lymphocytes in their lavage fluid did not stimulate normal B cells to produce immunoglobulin (P > 0.2, all comparisons). These findings suggest that in pulmonary sarcoidosis (a) the lung is an important site of immunoglobulin production; (b) activated lung T lymphocytes play an important role in modulating this local production of antibody, and thus are likely to modulate the polyclonal hyperglobulinemia observed in these individuals.
Successful Pneumocystis carinii pneumonia prophylaxis using aerosolized pentamidine in children with acute leukemia.
Authors: J Weinthal, J D Frost, G Briones, M S Cairo
Journal: Journal of Clinical Oncology (1994)

We report our experience replacing trimethoprim-sulfamethoxazole (TMP/SMX) with aerosolized pentamidine (AP) in 22 children with acute leukemia who could not tolerate TMP/SMX.Children (age 1 to 15 years) with acute leukemia during maintenance chemotherapy or post-bone marrow transplantation (BMT) receiving prophylaxis for Pneumocystis carinii pneumonia (PCP) with TMP/SMX received AP following prolonged neutropenia or allergy to TMP/SMX. Patients received 300 mg of AP monthly (children < 4 years received 150 mg) dissolved in 5 mL of distilled water over 20 to 30 minutes.Over a 3-year period, 358 courses of AP were administered over 10,124 observable days. AP was adequately tolerated on a monthly basis for prophylaxis against PCP in 22 children with acute leukemia. AP was demonstrated to be effective in preventing PCP. There were minimal side effects observed during this trial. The majority of children with acute lymphoblastic leukemia (ALL; 12 of 14 [86%]) undergoing maintenance chemotherapy were able to resume full-dose therapy.AP in children is well tolerated and shows high efficacy for PCP prophylaxis in children with leukemia. We conclude that AP should be considered as second-line PCP prophylactic therapy for children with acute leukemia in instances in which TMP/SMX cannot be tolerated. Phase III trials are required to determine its effect on dose intensification and event-free survival.
Naturally Occurring Monoclonal Antibodies and Their Therapeutic Potential for Neurologic Diseases
Authors: Bharath Wootla, Jens O. Watzlawik, Arthur E. Warrington, Nathan J. Wittenberg, Aleksandar Denic, Xiaohua Xu, Luke R. Jordan, Louisa M. Papke, Laurie J. Zoecklein, Mabel L. Pierce, Sang-Hyun Oh, Orhun H. Kantarci, Moses Rodriguez
Journal: JAMA Neurology (2015)

Modulating the immune system does not reverse long-term disability in neurologic disorders. Better neuroregenerative and neuroprotective treatment strategies are needed for neuroinflammatory and neurodegenerative diseases.To review the role of monoclonal, naturally occurring antibodies (NAbs) as novel therapeutic molecules for treatment of neurologic disorders.Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized clinical trials, and basic science reports, were identified in a PubMed search for articles about NAbs and neurologic disorders that were published from January 1, 1964, through June 30, 2015. We concentrated our review on multiple sclerosis, Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis.Many insults, including trauma, ischemia, infection, inflammation, and neurodegeneration, result in irreversible damage to the central nervous system. Central nervous system injury often results in a pervasive inhibitory microenvironment that hinders regeneration. A common targeted drug development strategy is to identify molecules with high potency in animal models. Many approaches often fail in the clinical setting owing to a lack of efficacy in human diseases (eg, less than the response demonstrated in animal models) or a high incidence of toxic effects. An alternative approach is to identify NAbs in humans because these therapeutic molecules have potential physiologic function without toxic effects. NAbs of the IgG, IgA, or IgM isotype contain germline or close to germline sequences and are reactive to self-components, altered self-components, or foreign antigens. Our investigative group developed recombinant, autoreactive, natural human IgM antibodies directed against oligodendrocytes or neurons with therapeutic potential for central nervous system repair. One such molecule, recombinant HIgM22, directed against myelin and oligodendrocytes completed a successful phase 1 clinical trial without toxic effects with the goal of promoting remyelination in multiple sclerosis.Animal studies demonstrate that certain monoclonal NAbs are beneficial as therapeutic agents for neurologic diseases. This class of antibodies represents a unique source from which to develop a new class of disease-modifying therapies.
18-F-fluorodeoxyglucose-positron emission tomography as a new approach to detect lymphomatous bone marrow.
Authors: F Moog, M Bangerter, J Kotzerke, A Guhlmann, N Frickhofen, S N Reske
Journal: Journal of Clinical Oncology (1998)

PURPOSE Bone marrow involvement in patients with malignant lymphoma is considered a sign of generalized disease with less favorable prognosis. Bone marrow biopsy (BMB), which represents the standard diagnostic procedure, however, is associated with a high rate of false-negative findings, which may lead to errors in management. The present study was undertaken to investigate the efficacy of positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG-PET) as a new method to evaluate bone marrow involvement in patients with malignant lymphoma. METHODS Seventy-eight consecutive, untreated patients with either non-Hodgkin's lymphoma (NHL; n = 39) or Hodgkin's disease (HD; n = 39) were prospectively evaluated. Static FDG-PET imaging was performed following application of 270 MBq (F-18)-FDG. Attenuation correction was performed in 63 of 78 patients. Visual evaluation was performed by two examiners unaware of the clinical data. Material for BMB (70 bilateral, 8 unilateral) was obtained from the posterior iliac crest. Discordant results of PET and biopsy were settled, when possible, on the basis of further biopsy or magnetic resonance imaging (MRI). RESULTS In addition to seven concordant positive and 57 concordant negative findings, biopsy revealed another four cases with bone marrow involvement not detectable by FDG-PET analysis (+5.1%). On the contrary, PET showed bone marrow areas of intensive FDG uptake that suggested bone marrow lymphoma in 10 patients with negative biopsies (+12.8%). In eight patients, FDG-PET findings were confirmed by either histologic verification (n = 4), MRI (n = 2), polymerase chain reaction (PCR) for rearranged immunoglobulin H sequences (n = 1), or clinical presentation (n = 1). Two cases remained unresolved. CONCLUSION The results indicate that FDG-PET has a high potential to detect bone marrow involvement in malignant lymphoma. Besides confirming lesions found at BMB, FDG-PET provided additional information, which, in eight of 78 patients (10.3%), led to an upgrade of the tumor stage.
Low dose diesel exhaust particle exposure exacerbates allergic asthma in young mice
Authors: Thomas Acciani, Eric Brandt, Patricia Pastura, Gurjit Hershey, Timothy Le Cras
Journal: European Respiratory Journal (2012)

Rationale: Recent epidemiological studies correlate traffic pollution with the development of asthma in a dose dependent manner. Diesel exhaust particles (DEP) comprise the majority of the particulate matter in air pollution, and DEP exposure augments allergic responses in adult animals. However, it is unclear if DEP exposure exacerbates allergic asthma in young animals and whether this is dose dependent.

Objective: To determine if DEP exacerbates allergic asthma in young mice and whether a low dose is as effective as a high dose.

Methods: Three week old Balb/c mice were exposed intratracheally 3 times a week for 3 weeks with DEP alone at a high and low dose (6 and 1.2mg/kg respectively), house dust mite (HDM; 0.8mg/kg) alone, or DEP high or low dose in combination with HDM. Data was collected 24 hours after the last exposure. DEP doses were based on exposure data from children in the Cincinnati Childhood Allergy and Air Pollution Study.

Results: High dose DEP alone increased neutrophilic influx into the lungs. Low dose DEP alone did not. Both high and low dose DEP combined with HDM exposure increased antigen specific IgE, lung inflammatory cell counts, airway hyperreactivity, goblet cells, Th2 cytokine levels, T cell activation, effector T cells, and activated myeloid dendritic cells. Interestingly, both doses of DEP with HDM increased lung IL-17A levels and T cells that stained positive for both IL-13 and IL-17, which have been associated with more severe asthma.

Conclusions: DEP exacerbated allergic responses in young mice and a low dose was as effective as a high dose when combined with HDM, although low dose DEP alone did not increase inflammatory cell counts compared to high dose DEP alone.
Tuberculosis associates with both airflow obstruction and low lung function: BOLD results
Authors: André F.S. Amaral, Sonia Coton, Bernet Kato, Wan C. Tan, Michael Studnicka, Christer Janson, Thorarinn Gislason, David Mannino, Eric D. Bateman, Sonia Buist, Peter G.J. Burney
Journal: European Respiratory Journal (2015)

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common.
Gene expression profiling can predict pathological complete response (pCR) to anthracycline-based therapy in estrogen- receptor (ER) negative breast cancer (BC) patients
Authors: C. Desmedt, F. André, E. Azambuja, B. Haibe-Kains, D. Larsimont, V. D'Hondt, A. Di Leo, M. Piccart, L. Pusztai, C. Sotiriou
Journal: Journal of Clinical Oncology (2007)

10564 Background: Breast cancers show variable sensitivity to anthracycline (A)-based therapy. Here we aimed to identify gene expression profiles associated with pCR to this treatment. As it has repeatedly and consistently been shown that ER is the most dominant factor influencing the molecular composition of breast cancer, defining different types of BC disease and because we wanted to eliminate the confounding effect of indirect ovarian suppression in ER+ BC, we focused in this study on ER-negative patients only. Methods: We analyzed Affymetrix gene expression profiles generated from 132 ER- pre-treatment samples, constituting the largest series of ER- preoperatively A-treated BC (n=132/35 pCR). Sixty-two samples derived from the prospective multicentric TOP trial (epirubicin single-agent), 41 from Institut G. Roussy (retrospective selection/ FEC) and 27 from MD Anderson (prospective study/ FAC). Results: A student t- test analysis on the combined population of A-treated pts was performed identifying 102 genes that were significantly associated with pCR (p&lt;.01). These genes were mainly involved in cell death, DNA replication and recombination, molecular transport, cell cycle and morphology. Interestingly, 14 of these genes were located on the topoIIa amplicon. Of interest, none of these 14 genes seem to carry any prognostic value in untreated ER- pts (N=161). When we considered gene expression indices for specific A-targets such as topoIIa and helicase, we found that both were associated with pCR. However, subgroup analysis revealed that topoIIa index was predictive in ERBB2+ but not in ERBB2- subgroup. None of the genes from the adriamycin predictor (Potti et al.) or the p53 signature (Miller et al.) were significantly associated with pCR. Conclusions: This study suggests that a group of genes associated with topoIIa can identify ER-negative BC pts likely to respond to A-based therapy. These promising results are currently being validated in a larger series. No significant financial relationships to disclose.
Phase I Trial of Escalating Doses of Paclitaxel Combined With Fixed Doses of Cisplatin and Doxorubicin in Advanced Endometrial Cancer and Other Gynecologic Malignancies: A Gynecologic Oncology Group Study
Authors: Gini F. Fleming, Jeffrey M. Fowler, Steven E. Waggoner, Larry J. Copeland, Benjamin E. Greer, Ira Horowitz, Gregory Sutton, Russell J. Schilder, Paula M. Fracasso, Harrison G. Ball, William P. McGuire
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The primary objective of this phase I trial was to determine the feasibility of administering a combination of paclitaxel, cisplatin, and doxorubicin with or without granulocyte colony-stimulating factor (G-CSF) in patients with advanced endometrial and other gynecologic cancers. PATIENTS AND METHODS: Patients were chemotherapy-naive. Doxorubicin was administered as a brief infusion, paclitaxel for 3 hours, and cisplatin for 60 minutes. Treatments were repeated every 3 weeks. For most dose levels, the cisplatin and doxorubicin were fixed at 60 mg/m 2 and 45 mg/m 2 , whereas the paclitaxel was escalated in successive cohorts from 90 to 250 mg/m 2 . Patients who had received previous radiotherapy to the whole pelvis were escalated separately from those who had not. RESULTS: Eighty patients received 320 cycles of therapy. When G-CSF was not used, myelosuppression prevented escalation beyond the starting dose for patients with or without previous pelvic radiotherapy. When G-CSF was added, neurotoxicity became dose-limiting for both groups. Ten patients were removed from the study for asymptomatic declines in ejection fraction, but no symptomatic congestive heart failure was observed. Major antitumor responses occurred in 46% of patients (six of 13) with measurable endometrial carcinoma and 50% of patients (eight of 16) with measurable cervical carcinoma. CONCLUSION: The combination of paclitaxel, doxorubicin, and cisplatin at relevant single-agent doses is active and feasible with the addition of G-CSF. A regimen of cisplatin 60 mg/m 2 , doxorubicin 45 mg/m 2 , and paclitaxel 160 mg/m 2 with G-CSF support is recommended for further testing.
Effect of a High-Protein-Low-Carbohydrate Diet on Toxicity and Antitumor Activity of 5-Fluorouracil in Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: D T Flanigen-Roat, R J Milholland, M M Ip
Journal: JNCI Journal of the National Cancer Institute (1985)

The effect of different levels of dietary protein on 5-fluorouracil (FUra) toxicity and antitumor activity was assessed in female (BALB/c X DBA/2Ha)F1 (CDF1) and BALB/c mice bearing the P1798 lymphosarcoma. In the toxicity experiments, CDF1 mice were fed diets containing 5% [low protein (LP)], 20% [normal protein (NP)], or 60% [high protein (HP)] casein for 22 days and were then given a single ip injection of 275 mg FUra/kg. As determined by effects on the white blood cell count and by changes in body weight, FUra was least toxic in mice fed the HP diet. Moreover, mortality was 77.0, 42.9, and 11.4% for mice fed the LP, NP, and HP diets, respectively. In the antitumor studies, BALB/c mice bearing the P1798 lymphosarcoma were fed one of the 3 diets starting 5 days after transplant. Mice were given injections of 50 mg FUra/kg or the vehicle control on days 14 and 15 after transplant. As measured by tumor weights on day 16, FUra was least effective in mice fed the LP diet and most effective in mice fed the NP and HP diets. Survival time of mice given injections of FUra on days 14 and 15 was increased when compared to the survival time of control mice, but no difference in the percent increase in survival time was noted among the 3 dietary groups. If mice were given two cycles of FUra therapy (days 14 and 15 and days 20 and 21), mice fed the HP diet survived significantly longer than did mice fed the LP or NP diet. These data demonstrate that the feeding of an HP diet markedly decreases the toxicity of FUra while preserving or actually enhancing the antitumor effect.
TBCRC 019: A Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel with or without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients with Triple-Negative Breast Cancer
Authors: Andres Forero-Torres, Katherine E. Varley, Vandana G. Abramson, Yufeng Li, Christos Vaklavas, Nancy U. Lin, Minetta C. Liu, Hope S. Rugo, Rita Nanda, Anna M. Storniolo, Tiffany A. Traina, Sujata Patil, Catherine H. Van Poznak, Julie R. Nangia, William J. Irvin, Helen Krontiras, Jennifer F. De Los Santos, Paul Haluska, William Grizzle, Richard M. Myers, Antonio C. Wolff
Journal: Clinical Cancer Research (2015)

Tigatuzumab (TIG), an agonistic anti-DR5 antibody, triggers apoptosis in DR5(+) human tumor cells without crosslinking. TIG has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents. This study evaluates activity of TIG and chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).Randomized 2:1 phase II trial of albumin-bound paclitaxel (nab-PAC) ± TIG in patients with TNBC stratified by prior chemotherapy. Patients received nab-PAC weekly × 3 ± TIG every other week, every 28 days. Primary objective was within-arm objective response rate (ORR). Secondary objectives were safety, progression-free survival (PFS), clinical benefit, and TIG immunogenicity. Metastatic research biopsies were required.Among 64 patients (60 treated; TIG/nab-PAC n = 39 and nab-PAC n = 21), there were 3 complete remissions (CR), 8 partial remissions (PR; 1 almost CR), 11 stable diseases (SD), and 17 progressive diseases (PD) in the TIG/nab-PAC arm (ORR, 28%), and no CRs, 8 PRs, 4 SDs, and 9 PDs in the nab-PAC arm (ORR, 38%). There was a numerical increase in CRs and several patients had prolonged PFS (1,025+, 781, 672, 460, 334) in the TIG/nab-PAC arm. Grade 3 toxicities were 28% and 29%, respectively, with no grade 4-5. Exploratory analysis suggests an association of ROCK1 gene pathway activation with efficacy in the TIG/nab-PAC arm.ORR and PFS were similar in both. Preclinical activity of TIG in basal-like breast cancer and prolonged PFS in few patients in the combination arm support further investigation of anti-DR5 agents. ROCK pathway activation merits further evaluation.
High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009–2011
Authors: L. Skoura, S. Metallidis, D. Pilalas, A. Kourelis, A. Margariti, E. Papadimitriou, Z.A. Antoniadou, T. Chrysanthidis, O. Tsachouridou, P. Kollaras, P. Nikolaidis, N. Malisiovas
Journal: Clinical Microbiology and Infection (2012)
Mass antibiotic treatment to stop an outbreak of meningococcal disease: a molecular analysis
Authors: L.H. Katz, A. Zelazny, S. Scharf, A. Hourvitz, N. Asor, Y. Arbeli, S. Yust-Katz, G. Smollan-Fredman, M. Gdalevich
Journal: Clinical Microbiology and Infection (2007)