tbuckley/cabot-search huggingface dataset:
The Treatment of Cushing's Disease
Authors: Rosario Pivonello, Monica De Leo, Alessia Cozzolino, Annamaria Colao
Journal: Endocrine Reviews (2015)

Abstract Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery, and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease; or as postsurgical treatment, in cases of failure or incomplete surgical tumor resection; or as bridging therapy before, during, and after radiotherapy while waiting for disease control; or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analog pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of Cushing's syndrome when associated with impairment of glucose metabolism in case of the lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.
An evaluation of the needs of carers of people with COPD
Authors: Paul Cafarella, Tanja Effing, Peter Frith
Journal: European Respiratory Journal (2012)

Introduction: Many COPD patients are dependent on carers. Whilst the role of caring can be very demanding, surprisingly little is known about the needs of carers of COPD patients and hence this was the main aim of this study. Methods: 21 patient-carer dyads recruited from databases at Repatriation General Hospital completed questionnaires and carers attended focus group meetings. Results: Carers (mean age 71.1, SD 9.8) completed the Short-Form 36 (SF36: Physical Component Score (PCS) 41.1, SD 11.4; Mental Component Score (MCS) 44.9, SD 9.2), and Hospital Anxiety and Depression scale (HADS: Anxiety 8.9, SD 3.3; Depression 5.1, SD 3). Patients (mean age 75.2, SD 7.6) completed the Chronic Respiratory Questionnaire (Dyspnoea 3.5, SD 1.2; Fatigue 3.5, SD 1.5; Emotional 4.3, SD 1.3; Mastery 4.5, SD 1.4), SF36 (PCS 25.7, SD 7; MCS 47.1, SD 11.9) and HADS (Anxiety 7.5, SD 3.4; Depression 6.5, SD 4). Thematic analysis of focus group transcripts indicated that carers emphasised physical and emotional impacts of their duties and identified social and work-related handicap as consequences. Carers believed that physical and/or emotional problems (either theirs or their patients9) as well as a lack of knowledge were significant barriers to their role. A lack of inclusion in patient treatment plans, particularly following hospital discharge, was also noted. Respite support, peer debriefing, counselling and respiratory disease education were identified as areas that would assist carers with their role. Discussion: Carer burden, handicap, lack of inclusion and knowledge were identified as issues that remain under-supported. The findings suggest the potential value of carer recognition, support and upskilling in COPD treatment planning.
Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome
Authors: Eve Henry, Victor Villalobos, Lynn Million, Kristin C. Jensen, Robert West, Kristen Ganjoo, Alexandra Lebensohn, James M. Ford, Melinda L. Telli
Journal: Journal of the National Comprehensive Cancer Network (2012)

Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.
A 1-year Aspergillus terreus surveillance study at the University Hospital of Innsbruck: molecular typing of environmental and clinical isolates
Authors: G. Blum, S. Perkhofer, K. Grif, A. Mayr, G. Kropshofer, D. Nachbaur, R. Kafka-Ritsch, M.P. Dierich, C. Lass-Flörl
Journal: Clinical Microbiology and Infection (2008)
Nutritional status and lipid parameters in COPD patients
Authors: Barbara Kuznar-Kaminska, Marcin Grabicki, Beata Brajer-Luftmann, Halina Batura-Gabryel
Journal: European Respiratory Journal (2012)

Aim of study was evaluation of nutritional status and lipid parameters in COPD patients and assessment the dependence between above.  114 COPD patients - 69 males (60,5%) and 45 females (39,5%) mean age 65,82, in different stages of the disease participated in the study. It was assessed nutritional status using bioimpedance method (Akern BIA 101) and concentrations of lipid parameters in blood serum. Malnutrition was confirmed in 17 (14,91%) patients, more frequent among women than man (58,8% vs 41,2%). Between patients with decreased FFMI normal BMI was confirmed in 9 individuals. Deviations in the level of serum lipids was found in 43 participants (37,71%) and it was the most often hypercholesterolemia (33,3%) - in 6 (5,26%) patients hypercholesterolemia with hypertriglicerydemia and 5 cases (4,38%) of hypertriglicerydemia only.  FMI (fat mass index) didn9t correlate with cholesterol serum level, as well as LDL and TAG levels; unlike the BMI, where weak correlation with cholesterol was noticed (p=0,02). FFMI correlated strongly with HDL cholesterol (p=0,004).  Deviations in lipid profile in COPD patients are not exclusively connected with fat contents but may be the consequence of systemic disease.
Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.
Authors: S M Pupa, R Bufalino, A M Invernizzi, S Andreola, F Rilke, L Lombardi, M I Colnaghi, S Ménard
Journal: Journal of Clinical Oncology (1996)

PURPOSE Experiments were designed to investigate the association between tumor leukocytic infiltrates with other pathologic and biologic variables in primary tumors and with prognosis, and to define the phenotype of the infiltrating leukocytes. PATIENTS AND METHODS A retrospective series of 1,207 primary breast carcinomas was studied according to different prognostic variables, including the presence of lymphoplasmacytic infiltrate (LPI). LPI was analyzed in association with other variables and survival. Additionally, a small prospective series of surgical specimens from 75 primary breast carcinomas with infiltrating leukocytes was tested by immunohistochemistry on frozen sections to phenotypically characterize the infiltrate, using anti-CD reagents, and the tumor, using anti-c-erbB-2 oncoprotein monoclonal antibody. RESULTS In the retrospective series, menopausal status, nodal status, tumor size, stage, grade, and p185HER2 overexpression but not LPI were found to be associated with prognosis and maintained their prognostic significance in a multivariate analysis. LPI was significantly associated with some of these independent prognostic factors, such as tumor size (P = .03), stage (P = .004), grade III carcinomas (P &lt; .000001), and overexpression of the p185HER2 (P &lt; .000001). In some subgroups of patients in whom LPI was found more frequently, such as grade III cases or N- and c-erbB-2-positive cases, LPI was found to be indicative of a good prognosis (P = .008 and P = .03, respectively). Phenotypic analysis of the infiltrating leukocytes revealed a preponderance of macrophages in high-grade (P = .05) or c-erbB-2-positive (P = .008) tumors, whereas T cells constituted most of the infiltrate in the other tumors. CONCLUSION Our data demonstrate different leukocytic types in the infiltrate of breast tumors with different prognostic significance.
Late-breaking abstract: Do trainee respiratory doctors under supervision achieve acceptable results with EBUS-TBNA?
Authors: Mohammed Alhajji, Peter J. Smith, Matthew Callister, Paul K. Plant
Journal: European Respiratory Journal (2011)

Background:  Endo-bronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is a useful tool in the staging and diagnosis of thoracic malignancy. There is limited evidence on the safety and efficacy of instructing respiratory trainee doctors in EBUS-TBNA.   Aims:  To compare the results obtained by trainee respiratory doctors performing EBUS-TBNA as principal operator supervised by consultant respiratory physicians, to the results obtained from consultants as principal operators. We aim to discover if trainees can perform this procedure with acceptable accuracy and safety.   Methods:  All EBUS reports were retrospectively collected between February 2009 and July 2010. The reports were analysed to determine the sensitivity, specificity and diagnostic accuracy for the EBUS operator, and rates compared for trainees, consultants and published series. Complication rates were also compared.   Results:  Overall sensitivity and diagnostic accuracy were similar for trainees as primary operator compared to consultants. There were no significant adverse events in either group (table1).   Conclusion:  Provided there is close supervision by a consultant, trainee respiratory doctors performing EBUS-TBNA as primary operators appear to have similar safety and efficacy results.
Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3
Authors: P. Singh, A. Benjak, S. Carat, M. Kai, P. Busso, C. Avanzi, A. Paniz-Mondolfi, C. Peter, K. Harshman, J. Rougemont, M. Matsuoka, S.T. Cole
Journal: Clinical Microbiology and Infection (2014)
Nasal nitric oxide measurement using continuous aspiration by hand-held device discriminates patients with primary ciliary dyskinesia from healthy subjects
Authors: Silvia Montella, Kjell Alving, Sara De Stefano, Laida Lisa Di Micco, Angela Di Giorgio, Francesca Santamaria
Journal: European Respiratory Journal (2012)

Background . Low nasal nitric oxide (nNO) has been reported in subjects with primary ciliary dyskinesia (PCD). Thus, nNO measurement has been proposed as a diagnostic tool to screen for PCD. The best validated method for nNO assessment is aspiration at a constant flow rate from one naris (Am J Respir Crit Care Med 2005;171:912-30). Traditionally, nNO is obtained using stationary chemiluminescence analysers. Hand-held electrochemical devices have been used in PCD for nNO analysis using the nasal exhalation method (silent and humming exhalation). No study compared nNO measured using continuous nasal aspiration in PCD and healthy subjects by a hand-held device.   Aim . To find out whether nNO measured by a hand-held analyser using the continuous aspiration method discriminates PCD from healthy subjects.   Methods . Twenty-three PCD patients (median age, 15.8 yrs; range, 4.6-32.8) and 23 healthy controls (age, 15.7 yrs; range, 4.3-32.1) measured nNO with a hand-held electrochemical device (NIOX MINO®, Aerocrine AB) during oral breathing through a mouthpiece.   Results . Median (range) nNO values were 12 (5-62) and 506 (215-777) ppb in PCD and controls, respectively ( p     Conclusion . Measurement of nNO by the hand-held device using the continuous aspiration method has an excellent sensitivity and specificity in distinguishing PCD from healthy subjects. Its wider use might result in an increased number of detected individuals suspected to have PCD.
Experimental Nude Mouse Model of Human Colorectal Cancer Liver Metastases&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Giavazzi, J M Jessup, D E Campbell, S M Walker, I J Fidler
Journal: JNCI Journal of the National Cancer Institute (1986)

A nude mouse model (BALB/c) was established for investigating the production of hepatic metastases by human colorectal carcinoma (HCC) cells. The malignant potentials of 3 different HCCs derived from a primary tumor (HCC-P4733), a lymph node metastasis (HCC-M14328), and a hepatic metastasis (HCC-M1410) were investigated following implantation into the spleens of athymic nude mice. Cells of the HCC-M1410 line produced extensive liver tumors in all mice by 30 days after injection. Cells of the HCC-M14328 and HCC-P4733 lines produced few liver tumors in the inoculated mice and then only after a 90-day period. Isozyme and karyotype analyses ascertained the human origin of all the tumors. Studies with [125I]ldUrd-labeled HT-29 carcinoma cells suggested that tumor cells reached the liver shortly after injection into the spleen. Thus the production of HCC tumors in livers of nude mice was determined by the ability of HCC cells to proliferate in the liver parenchyma rather than by the ability of the cells to reach the liver. The results suggest that the intrasplenic injection of HCC cells can provide a valuable model for the study of the biology and therapy of the liver metastases.
Successful Transplantation of Lymphosarcoma in Calves Treated With Antilymphocyte Serum&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W. J. Donawick, C. Johnstone, J. G. Martens, D. C. Dodd, J. E. Martin, R. R. Marshak
Journal: JNCI Journal of the National Cancer Institute (1970)
Multiple melanoma susceptibility factors function in an ultraviolet radiation response pathway in skin
Authors: N. Giles, S. Pavey, A. Pinder, B. Gabrielli
Journal: British Journal of Dermatology (2011)

Summary Background Exposure to ultraviolet radiation (UVR) and the familial melanoma susceptibility gene p16 (CDKN2A) are among the major risk factors which have been identified to contribute to the development of melanoma, and also significantly contribute to squamous cell carcinoma. We have previously shown that UVR induces p16CDKN2A expression in melanoma and keratinocyte cell lines and human skin, but the regulatory mechanisms controlling this expression are unknown. Objectives To determine the mechanism by which UVR induces p16CDKN2A expression in melanocytes and keratinocytes in the epidermis. Methods We have used an in vitro cell lines model of the UVR response in skin to assess the changes in p16CDKN2A expression and the signalling pathways regulating these changes, and validated these findings in whole human skin cultures. Results We show that UVR-induced ERK signalling, mediated by BRAF, regulates p16CDKN2A expression at the transcriptional, and possibly translational level. Conclusions This study demonstrates the biological connection between the known melanoma genes p16 (CDKN2A) and BRAF in a normal physiological response to UVR in the skin, and highlights the importance of defects in this biological pathway to melanoma and squamous cell carcinoma development.
Cysts of the Epididymis, Cancer of the Cervix, Granular Cell Myoblastoma, and Other Lesions After Estrogen Injection in Newborn Mice
Authors: Thelma B. Dunn, Arleigh W. Green
Journal: JNCI Journal of the National Cancer Institute (1963)

Male and female mice from a noninbred Swiss colony and from inbred strains BALB/c and C3Hf (without the milk agent) were given injections of diethylstilbestrol on the day of birth. When autopsies were performed from 13 to 26 months later, lesions of the epididymis were found in over half the male mice. The female mice had histologic evidence of continuous estrogen stimulation, formation of concretions in the vagina, carcinoma of the uterine cervix and vagina, and there were two cases of granular cell myoblastoma located at the uterine cervix. Two cervical cancers and one granular cell myoblastoma were successfully transplanted. One strain C3Hf female, age 26 months, that received an injection of saline alone on the day of birth had a granulosa cell tumor of the ovary, evidence of continuous estrogen stimulation, an epidermoid cancer near the vaginal orifice, and a small granular cell myoblastoma beneath the epithelium of the uterine cervix.
Neoplastic Conversion and Chromosomal Characteristics of Rat Embryo Cells &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Jay L. Jackson, Katherine K. Sanford, Thelma B. Dunn
Journal: JNCI Journal of the National Cancer Institute (1970)

ALB/N rat-embryo cells, presumably free of murine leukemia virus and grown in a chemically defined medium (CDM) supplemented with serum, underwent “spontaneous” neoplastic conversions in vitro. Cell lines in CDM with horse serum (HS) supplement converted after 9-30 months in vitro, a period significantly longer than that reported for mouse embryo cells in this type medium. From the same embryo cell pool, 1 of 2 lines on CDM with fetal calf serum supplement underwent neoplastic conversion as compared with 3 of 3 lines on HS medium within a period of 412 days, and the cells grown in HS medium produced tumors with shorter latent periods. Cells derived from frozen-thawed cultures converted earlier than those not frozen. Tumor production from the tissue culture cells tended to vary directly with period of culture in vitro. Cells grown on un-supplemented CDM did not convert during the same period (11–38 months) in which the more rapidly dividing lines in serum-supplemented medium did. Cells in HS medium carried with limited or no subculturing, which continued to grow as dense, multilayered cell sheets, did not convert. In the subcultured lines, after an initial period of karyotypic stability (61–110 days), extensive chromosomal alterations occurred. We found no chromosomal alteration or pattern of chromosome change that could be correlated with the neoplastic conversion of the cells.
A single-compartment model cannot describe passive expiration in intubated, paralysed humans
Authors: G L Chelucci, F Brunet, J Dall'Ava-Santucci, J F Dhainaut, D Paccaly, A Armaganidis, J Milic-Emili, A Lockhart
Journal: European Respiratory Journal (1991)

The time-course of thoracic volume changes (respiratory inductive plethysmograph) during relaxed expiration was studied in 11 intubated, paralysed, mechanically ventilated subjects. The semilog volume-time curves show that expiration is governed by two apparently separate mechanisms: one causes emptying of most of the expired volume (approximately 80%) with a time constant of 0.50 +/- 0.22 s for a baseline tidal volume of 0.44 +/- 0.12 l (mean +/- SD) and 0.37 +/- 0.14 s when the tidal volume is reduced (VTP); the other contributes a relatively small amount to the expired volume over a significantly longer time, the time constant amounting to 3.27 +/- 1.54 s for baseline VT and 2.95 +/- 1.65 s for VTp. The first mechanism probably reflects the standard elastic and flow resistive properties of the respiratory system, while the second, slower compartment, is probably an expression of the viscoelastic properties of the pulmonary and chest wall tissues.
Comorbidities and MDR-TB treatment outcomes in Georgia- 2009-11 cohort
Authors: Marina Kikvidze, Lali Ikiashvili
Journal: European Respiratory Journal (2014)

Background. Treatment of MDR-TB is complex and chemotherapy course9s outcome depends on many factors. Comorbidities may complicate TB disease and effect treatment response.  Aims and objectives. The aim of the study was comparison of chemotherapy response among patients with and those without comorbidities in a setting of individualized MDR-TB care and adequate management of all diseases.  Methods. We conducted a retrospective cohort study of 1970 drug-resistant tuberculosis patients integrated in DOTS+ programme in 2009-2011 years in Georgia. Patients were routinely investigated for HIV, diabetes mellitus (DM) and viral hepatitis. Documentary approved diagnoses of other diseases were taken in account. Dispersive analysis using Mann-Whitney/Wilcoxon Two-Sample Test was provided to compare the treatment outcomes of patients with and those without comorbidity.  Results. Of 1970 patients with drug-resistant tuberculosis 486(24,7%) had one or more comorbidity. 223 patient(11,3%) had liver diseases, DM-104(5,2%), HIV-72(3,7%), Psychiatric diseases - 53(2,7%), other-55(2,9%). Definition “success” received 966(49%) patient:44,0% with comorbidities vs 50,7%-without(p=0,01),“Default”-30,5% vs 28,4%, “Failure”- 4,1% vs 4,0(p>0,05, CI-95%),“Death”- 10,7% vs 5,7%(p  Conclusions. Our cohort study revealed that comorbidities had serious impact on treatment outcomes andwere associated with significant lower successful treatment outcomes and about twice higher death rate.
Characterization of allergic airway inflammation in patients with COPD using fractional exhaled nitric oxide levels
Authors: James Donohue, Samantha Earnhart, Nancy Herje, Paul Dorinsky
Journal: European Respiratory Journal (2013)

Rationale: Asthma can coexist with chronic obstructive pulmonary disease (COPD), particularly in older adults, a condition labeled the overlap syndrome (OS). Additionally, while airway inflammation in COPD is generally neutrophilic, COPD patients may have features of asthma and thus a component of allergic airway inflammation. This study characterized allergic airway inflammation in patients with COPD using fractional exhaled nitric oxide (FeNO).  Methods: A single-visit, outpatient study in 191 subjects age 40 years and older with COPD or the overlap syndrome. All subjects performed spirometry and FeNO testing. Subjects were classified as have COPD/asthma, COPD or COPD/emphysema using ICD codes.  Results: The subjects had a mean age of 63.9 ± 11.3 years, a mean smoking history of 46 ± 29 pack years and a mean FEV1 % predicted of 53.9 ± 22.1%. A total of 32% of subjects were classified as mixed COPD/asthma, 42% as COPD and 26% as COPD/emphysema. The mean FeNO level for all subjects was 15.3 ± 17.2 ppb. FeNO level versus diagnosis are shown below.  Conclusions: These data indicate that increases in FeNO do occur in patients with COPD and increases in FeNO to intermediate or high levels occurred in 21 of 191 subjects (11%) in this study. Increases in FeNO were most common in subjects with mixed COPD/asthma. Since FeNO is useful for identifying patients with allergic airway inflammation who will have a beneficial response to treatment with an ICS, these data may have important implications for the management of COPD patients.