tbuckley/cabot-search huggingface dataset:
Breast conservation and prolonged chemotherapy for locally advanced breast cancer: the University of Michigan experience.
Authors: S D Merajver, B L Weber, R Cody, D Zhang, M Strawderman, K A Calzone, V LeClaire, A Levin, J Irani, M Halvie, D August, M Wicha, A Lichter, L J Pierce
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured by survival and rate of breast conservation. MATERIALS AND METHODS Eighty-nine patients with stage III disease were enrolled at the University of Michigan (UM) onto a prospective nonrandomized trial. Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to 14. Patients with a negative biopsy received radiation only, while those with residual disease underwent mastectomy and postoperative radiotherapy. Eight more cycles of chemohormonal therapy were administered after local-regional therapy. RESULTS The clinical response rate to neoadjuvant therapy was 97%, 28% of patients had a complete pathologic response evaluated at biopsy. Five-year overall and disease-free survival probabilities were 54% and 44%, respectively. The median disease-free survival time was 2.4 years. The 5-year actuarial rates of local-regional control with local failure as only first failure were 82% and 78% following radiotherapy, and mastectomy and radiotherapy, respectively (P = .99). CONCLUSION Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC, with 28% of patients being candidates for breast conservation and a 5-year overall survival rate of 54%.
The isolation and characterization of non-typeable Haemophilus influenzae from the sputum of adult cystic fibrosis patients
Authors: D Bilton, A Pye, MM Johnson, JL Mitchell, M Dodd, AK Webb, RA Stockley, SL Hill
Journal: European Respiratory Journal (1995)

The role of non-typeable Haemophilus influenzae in cystic fibrosis (CF) remains unclear. We wanted, therefore, to determine the presence and characteristics of non-typeable H. influenzae in sputum samples from patients with CF. In order to do this, we have assessed sputum samples from 55 consecutive clinically stable patients seen routinely at an adult CF out-patient clinic. Quantitative bacterial culture was performed using a selective media containing cefsoludin, and isolates were characterized by biotyping and outer membrane protein profile analysis. In 17 (30%) of these samples, non-typeable H. influenzae was isolated and was present in similar viable numbers (mean 7.7 x 10(8) colony-forming units (cfu).mL-1; SEM 3.1) to Pseudomonas aeruginosa (mean 8 x 10(8) cfu.mL-1: SEM 2.4). All non-typeable H. influenzae isolates recovered were beta-lactamase negative and sensitive to a range of antibiotics. Several biotypes and outer membrane protein profiles were observed, with no apparent association between these two phenotypic characteristics. The study showed that large numbers of non-typeable H. influenzae are often present in sputum from adult patients with CF. Further longitudinal studies of outer-membrane protein profile analysis are required to determine the dynamics of non-typeable H. influenzae colonization in individual patients and the clinical significance.
Extending Positron Emission Tomography Scan Utility to High-Risk Neuroblastoma: Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography as Sole Imaging Modality in Follow-Up of Patients
Authors: Brian H. Kushner, Henry W.D. Yeung, Steven M. Larson, Kim Kramer, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Although positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ( 18 F-FDG) has a major impact on the treatment of adult cancer, the reported experience with extracranial tumors of childhood is limited. We describe a role for PET in patients with neuroblastoma (NB). PATIENTS AND METHODS: In 51 patients with high-risk NB, 92 PET scans were part of a staging evaluation that included iodine-123 or iodine-131 metaiodobenzylguanidine (MIBG) scan, bone scan, computed tomography (and/or magnetic resonance imaging), urine catecholamine measurements, and bone marrow (BM) examinations. The minimum number of tests sufficient to detect NB was determined. RESULTS: Of 40 patients who were not in complete remission, only 1 (2.5%) had NB that would have been missed had a staging evaluation been limited to PET and BM studies, and 13 (32.5%) had NB detected by PET but not by BM and urine tests. PET was equal or superior to MIBG scans for identifying NB in soft tissue and extracranial skeletal structures, for revealing small lesions, and for delineating the extent and localizing sites of disease. In 36 evaluations of 22 patients with NB in soft tissue, PET failed to identify only two long-standing MIBG-negative abdominal masses. PET and MIBG scans showed more skeletal lesions than bone scans, but the normally high physiologic brain uptake of FDG blocked PET visualization of cranial vault lesions. Similar to MIBG, FDG skeletal uptake was diffusely increased with extensive or progressing BM disease but faint or absent with minimal or nonprogressing BM disease. CONCLUSION: In the absence or after resolution of cranial vault lesions, and once the primary tumor is resected, PET and BM tests suffice for monitoring NB patients at high risk for progressive disease in soft tissue and bone/BM.
Effect of hypoxia on proliferation and VEGF-release of human bronchial smooth muscle cells
Authors: Laura Keglowich, Michael Roth, Michael Tamm, Pieter Borger
Journal: European Respiratory Journal (2013)

Background: Airway wall remodeling, an important asthma pathology, includes basement membrane thickening. This may lead to hypoxia in the sub-epithelial cells layer. Increased levels of hypoxia-inducible factor alpha in endobronchial biopsies and BALF of asthmatics support this hypothesis.  Objective: In our study we investigate the effect of hypoxia on proliferation of human bronchial smooth muscle cells (BSMC) and on the release of VEGF.  Methods: BSMC have been stimulated with 5% FCS under normoxic (21% O2) or hypoxic (1% O2) conditions. Proliferation was determined by cell counts. The release of VEGF from BSMC was analyzed by ELISA. Proliferating Cell Nuclear Antigen (PCNA) was detected by immunoblots.  Results: Proliferation of FCS-stimulated BSMC was significantly increased. Hypoxia significantly reduced the FCS-induced proliferation by 56.70 ± 5.53%. Analysis of protein levels of PCNA reflects the observed proliferation-inhibition. After 24h PCNA protein-levels of BSMC under hypoxic conditions significantly decreased (43 ± 18%; p = 0.033). The VEGF release from FCS-stimulated BSMC under hypoxia was significantly increased (3.58 ± 0.66; p = 0.001).  Conclusion: Hypoxia led to reduced proliferation of FCS-stimulated BSMC. BSMC hyperplasia, one feature of airway wall remodeling in asthmatics, can therefore not be linked directly to the proliferative stimulus of hypoxia as suggested by others. Our data suggest that BSMC hyperplasia in asthma is indirectly induced by hypoxia through VEGF-dependent angiogenesis and increased nutrition supply.
Inflammatory Bowel Disease in Children and Adolescents
Authors: Michael J. Rosen, Ashish Dhawan, Shehzad A. Saeed
Journal: JAMA Pediatrics (2015)

The inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn disease, are chronic inflammatory disorders of the gastrointestinal tract most often diagnosed in adolescence and young adulthood, with a rising incidence in pediatric populations. These disorders are common enough in children that most pediatricians and other pediatric clinicians will encounter children with IBD in their general practice. Inflammatory bowel disease is caused by a dysregulated mucosal immune response to the intestinal microflora in genetically predisposed hosts. Although children can present with the classic symptoms of weight loss, abdominal pain, and bloody diarrhea, many present with nonclassic symptoms of isolated poor growth, anemia, or other extraintestinal manifestations. Once IBD is diagnosed, the goals of therapy consist of eliminating symptoms, normalizing quality of life, restoring growth, and preventing complications while minimizing the adverse effects of medications. Unique considerations when treating children and adolescents with IBD include attention to the effects of the disease on growth and development, bone health, and psychosocial functioning. The purpose of this review is to provide a contemporary overview of the epidemiologic features, pathogenesis, diagnosis, and management of IBD in children and adolescents.
Symptom profile of exacerbations in earlier and later COPD
Authors: James Allinson, Gavin Donaldson, Anant Patel, Beverly Kowlessar, Alex Mackay, Richa Singh, Simon Brill, Jadwiga Wedzicha
Journal: European Respiratory Journal (2013)

Characterising exacerbations in early COPD may identify targets to modify disease trajectory. We investigated if exacerbation characteristics differ between “earlier”(FEV1>60%predicted) and “later”(FEV1  Daily symptom diary card and clinic visit data were prospectively collected for 211 patients in the London COPD Cohort over seven years. Exacerbations were defined as previously(Seemungal 2000).  The earlier group (n=63;56 with≥1exacerbation) had fewer exacerbations(Table1) and reported more cold and sore throat symptoms than the later group (n=148;136 with≥1exacerbation)(Table2&Fig1). Demographics, active smoking and chronic bronchitis were similar between groups.  Higher prevalence of viral symptoms at exacerbation in earlier COPD suggests differences in viral susceptibility compared to later COPD.
<i>Mycobacterium abscessus</i> Infection in Cystic Fibrosis
Authors: ANNE R. CULLEN, CAROLYN L. CANNON, EUGENE J. MARK, ANDREW A. COLIN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We present a case of a patient with cystic fibrosis who was thought to be colonized with Mycobacterium abscessus for 13 yr prior to developing clinically apparent mycobacterial infection. However, histologic evidence indicated that invasive mycobacterial disease was present from the onset. While accepting that chronic endobronchial colonization with atypical mycobacteria may occur in patients with cystic fibrosis, the repeated isolation of mycobacteria from the sputum of these patients should alert the clinician to the possibility of indolent disease. Early consideration of treatment for this infection should occur in any patient with cystic fibrosis in whom there is an unexplained deterioration in lung function. The recent introduction of high dose ibuprofen raises concerns about its possible contribution to the progression of the infection. Cullen AR, Cannon CL, Mark EJ, Colin AA. Mycobacterium abscessus infection in cystic fibrosis: colonization or infection?
Breast Cancer Treatment with Everolimus and Exemestane for Er+ Women - Results of the 2Nd Interim Analysis of the Non-Interventional Trial Brawo
Authors: P.A. Fasching, T. Decker, A. Schneeweiss, C. Uleer, F. Förster, P. Wimberger, C.M. Kurbacher, N. Harbeck, O. Tomé, B. Müller, C. Mundhenke, S. Kümmel, M. Muth, J. Kreuzeder, W. Bloch, H. Tesch, D. Lüftner, C. Jackisch, F. Schütz, E. Grischke
Journal: Annals of Oncology (2014)
Assault Patients Attending a Scottish Accident and Emergency Department
Authors: John Wright, Ash Kariya
Journal: Journal of the Royal Society of Medicine (1997)

Over 2 months in 1995, 235 assault patients attended the accident and emergency department of the Royal Alexandra Hospital, Paisley (2.4% of total new attendances). 80% were male and their mean age was 28 years (range 6-64); men were the assailants in over 90% of attacks. Alcohol had been consumed by 69% of the victims and 9% admitted to taking illicit drugs. The commonest place of assault was the street (44%) but women were more likely to be assaulted in their homes. Penetrating weapons were used in 23% of assaults. 60% of all injuries were to the head and neck. 27% of the victims were admitted to hospital. Paisley has an assault rate similar to that of other UK centres but the use of penetrating weapons is much higher than elsewhere.
The utility of bronchoscopically acquired tissue for successful lung cancer molecular profiling (LC-MP)
Authors: Yuan Zhang, Mingying Zeng, Peter Illei, Qing Li, Zahra Maleki, Christina Adams, Anna Novak, Susan Otell, Rex Yung
Journal: European Respiratory Journal (2013)

Background: Molecular profiling of NSCLC is key to personalized LC therapy. Until now, the focus has been on EBUS- TBNA sampling of regional Lymph Nodes. This study compares tissue from primary lung cancers Vs LNs for successful lung cancer molecular profiling (LC-MP).

Methods: Retrospective review of primary lung adenocarcinomas diagnosed bronchoscopically by single physician (RY). Tissue adequacy was determined by pathologists (K.L; P.I) who selected the best source of material for LC-MP. The cases were tested sequentially for KRAS, followed by EGFR, ALK and on occasion BRAF.

Results: 54 cases of adenoCA, & 7 Not-Otherwise-Specified CAs from 94 NSCLC were analyzed. 36 of these 61 cases (59%) had adequate tissue for LC-MP testing. KRAS+: 14/36 (39%), EGFR +:7/36 (19%), ALK+ : 2/36 (6%) and BRAF+ : 1/36(3%) .

![Figure][1] 



In these 36 patients, we tried 80 approaches with different biopsy techniques and had 69 positive tumor sample sources, Pathologists preferentially selected primary LC biopsies in 80% of cases (47% Transbronchial forceps bx; 25% Endobronchial bx; 8% TBNA extrabronchial central tumor) and 20 % from LNs (EBUS-TBNA) for LCMP.

Conclusion: Primary LC tissue obtained from transbronchoscopic biopsy techniques are suitable and sufficient for multiple cancer biomarkers, and are often preferred over LNs for molecular profiling. Multi-source sampling is recommended at time of initial tissue diagnosis.

 [1]: pending:yes
Effects of interleukin-2 immunotherapy on renal function.
Authors: G A Kozeny, J D Nicolas, S Creekmore, L Sticklin, J E Hano, R I Fisher
Journal: Journal of Clinical Oncology (1988)

Recombinant interleukin-2 (IL-2) infusions have recently been evaluated as a new form of immunotherapy for the treatment of malignancies. This form of therapy has been complicated by the development of fluid retention, azotemia, and hypophosphatemia. To evaluate the effects of IL-2 on renal function, we prospectively studied eight patients who received IL-2 (10(5) micron/kg every eight hours intravenously [IV]) for five days as the initial phase of a treatment protocol using IL-2 plus lymphokine activated killer (LAK) cells. Dopamine and fluids were used to maintain blood pressure and all patients received indomethacin (100 mg/d). IL-2 therapy produced a syndrome similar to endotoxemia with the development of respiratory alkalosis (pH = 7.44 +/- .2, pCO2 = 30 +/- 2) and hypotension (mean BP, 71.3 mm Hg). These changes were accompanied by marked sodium avidity, edema formation, and mild elevations of BUN and creatinine. Hypophosphatemia, hypocalcemia, and hypomagnesemia were commonly seen. No defects in renal calcium, magnesium, phosphorous, net acid excretion, or glycosuria were demonstrated. We conclude: (1) IL-2 induces an increase in vascular permeability causing the development of edema, sodium avidity, and prerenal azotemia as occurs during endotoxemia; (2) IL-2 therapy induces respiratory alkalosis with the subsequent intracellular shift of phosphorous accompanied by increased renal phosphorous reabsorption; and (3) there is no evidence of renal tubular dysfunction (renal tubular acidosis [RTA], renal leak of glucose, phosphorous, or magnesium).
Macrophage-Mediated Destruction of Human Malignant Cells In Vivo&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: P W Mansell, H Ichinose, R J Reed, E T Krementz, R McNamee, N R Di Luzio
Journal: JNCI Journal of the National Cancer Institute (1975)

Macrophages require a plasma component, designated "recognition factor" (RF), for the expression of optimal function. The RF activity was profoundly depleted in plasma from patients with malignant disease, and the degree of depletion and the severity of the malignant state seemed to be related. Since experiments demonstrated that an active RF significantly inhibited tumor growth, clinical studies were initiated to investigate the influence of intratumor administration of an active RF fraction. Glucan, a potent macrophage activator, was also employed alone or combined with RF. These studies were undertaken to enhance the recognition of malignant cells by macrophages and to mobilize and activate macrophages intralesionally. The initial 9 patients studied had malignant melanoma, adenosquamous carcinoma of the lung, or carcinoma of the breast. Control and experimental lesions were injected; subsequently biopsies were performed at varying intervals for histologic evaluation. Always when glucan or glucan and RF fraction were administered intralesionally, the size of the lesion was strikingly reduced in as short a period as 5 days. This reduction was associated with necrosis of the tumor and a monocytic infiltrate. In small lesions, resolution was complete, whereas in large lesions, resolution was partial. The amount of glucan injected and the quantity of residual tumor appeared to be related. The induced necrosis of the tumor nodule was associated with an increase in plasma levels of circulating RF activity.
Factors Affecting Suppressor Cell Activity in Tumor-Allosensitized Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bertie F. Argyris
Journal: JNCI Journal of the National Cancer Institute (1980)

Adult C57BL/6 mice inoculated with P-815 mastocytoma cells developed splenic suppressor cells. These suppressor cells were assayed in mixed lymphocyte cultures. Suppressor cells appeared earlier and became more active after sensitization with low doses of allogeneic tumor. After low doses of tumor cells, the suppressor cell activity developed before cytotoxic activity, whereas after higher doses of tumor cells, suppressor and cytotoxic activity appeared simultaneously. The suppressor cells were not H-2 restricted but did express their activity stronger in the presence of the specific (H-2d) alloantigen. Neonatally thymectomized adult C57BL/6 mice failed to develop splenic suppressor cell activity after tumor allosensitization. This suggested that the thymus is a source for suppressor precursor cells. These precursor cells remained active in the spleen up to 3 1/2 months after adult thymectomy. Suppressor factor was released in cultures of tumor-allosensitized spleen cells. The presence of a specific (H-2d) alloantigen improved the relase of suppressor factor (SF). Cultures of tumor-allosensitized spleen cells, enriched for T-cells, contained more SF. SF was not H-2 restricted or antigen-specific.
Insulin-Like Growth Factor I Plays a Role in Regulating Erythropoiesis in Patients with End-Stage Renal Disease and Erythrocytosis
Authors: LEE-YUNG SHIH, JENG-YI HUANG, CHING-TAI LEE
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Erythroid progenitor growth, the serum hormones that regulate erythropoiesis, and the effect of patient's serum on the growth of normal erythroid progenitors were assessed in eight patients with end-stage renal disease (ESRD) and erythrocytosis. All patients were male and had been on maintenance dialysis, they had a hematocrit &gt;50% and/or a red blood cell count &gt;6 × 10 12 /L and an arterial oxygen saturation &gt;95%. Four had acquired cystic disease of the kidney (ACDK), and four other non-ACDK patients did not have known causes of secondary erythrocytosis after appropriate investigations and long-term follow-up. The methylcellulose culture technique was used to assay the erythroid progenitor (BFU-E/CFU-E) growth. Serum erythropoietin (EPO) and insulin-like growth factor I (IGF-I) levels were measured by RIA. Paired experiments were performed to determine the effects of 10% sera from ESRD patients and control subjects on normal marrow CFU-E growth. The numbers of EPO-dependent BFU-E in marrow and/or blood of patients with ESRD and erythrocytosis were higher than those of normal controls. No EPO-independent erythroid colonies were found. Serum EPO levels were constantly normal in one patient and elevated in three patients with ACDK; for non-ACDK patients, EPO levels were normal or low in two patients and persistently increased in one, but fluctuated in the remaining one on serial assays. There was no correlation between serum EPO levels and hematocrit values. The serum IGF-I levels in patients with ESRD and erythrocytosis were significantly increased compared with normal subjects or ESRD patients with anemia. We found an inverse correlation between serum EPO and IGF-I levels. Sera from patients with ESRD and erythrocytosis exhibited a stimulating effect on normal marrow CFU-E growth. The stimulating effect of sera from patients who had a normal serum EPO level and an elevated IGF-I level could be partially blocked by anti-IGF-I. The present study suggests that IGF-I plays an important role in the regulation of erythropoiesis in patients with ESRD and erythrocytosis who did not have an increased EPO production.
Nrf2 is closely related to enhance bleomycin induced airway inflammatory responses caused by diesel exhaust particles in mice
Authors: Ying-Ji Li, Tkako Shimizu, Yukiyo Hirata, Hirofumi Inagaki, Yusuke Shinkai, Ken Takeda, Arata Azuma, Hajime Takizawa, Yamamoto Masayuki, Tomoyuki Kawada, Shoji Kudoh
Journal: European Respiratory Journal (2012)

Diesel exhaust particles (DEP) induced oxidative stress play an important role in proinflammatory reaction on airway. Nrf2 is involved in the transcriptional regulation of many antioxidant genes. In the present study, we investigated the effect of DEP on an experimental model of bleomycin (BLM)-induced airway inflammatory responses in both of Nrf2+/+ and Nrf2−/− mice.  BLM was administered IV to Both Nrf2+/+ and Nrf2−/− C57BL/6J mice at a dosage of 80 mg/kg body weight on day zero. Mice were exposed to 1mg/m 3  DEP for 8 hrs/day and 5 days/week. We designed two experimental groups as follows: group 1, BLM alone, clean air; group 2, BLM plus pre-4wks-DEP exposure. Cell populations in BALF were examined at 10 days after BLM injection. We also examined cytokine level in BALF by ELISA.  In the DEP exposed group, the percentage changes from BLM alone group in the total number of cells and macrophages remarkably increased in the both Nrf2+/+ and Nrf2−/− mice. There were DEP-laden alveolar macrophages number were significantly greater in Nrf2-/- than in Nrf2+/+ mice. The percentage changes from BLM alone group in the neutrophils increased in the both Nrf2+/+ and Nrf2−/− mice, the increased neutrophils were significantly greater in Nrf2-/- than in Nrf2+/+ mice. The percentage changes from BLM alone group in the TGF-beta level decreased in the Nrf2-/- than in Nrf2+/+ mice.  These findings suggest that DEP might be an important risk factor on the BLM induced lung injury, and Nrf2 might be an important genetic factor in the determination of susceptibility to BLM induced lung injury caused by DEP via regulating the macrophages defense mechanisms in mice.
Community-acquired pneumonia in immunocompromised older patients: incidence, causative organisms and outcome
Authors: D. Sousa, I. Justo, A. Domínguez, A. Manzur, C. Izquierdo, L. Ruiz, M. Nebot, J.-M. Bayas, J.-M. Celorrio, W. Varona, P. Llinares, E. Miguez, E. Sánchez, J. Carratalá
Journal: Clinical Microbiology and Infection (2012)