tbuckley/cabot-search huggingface dataset:
An Unusual 2-Tone Epidermal Cyst
Authors: Francesco Lacarrubba, Anna Elisa Verzì, Aurora Tedeschi, Rosario Caltabiano, Giuseppe Micali
Journal: JAMA Dermatology (2015)

This case report describes an unusual, clinically 2-tone epidermal cyst that displayed an irregular blue color under dermoscopy, reflectant platelike structures under confocal microscopy, and cholesterol clefts histopathologically.
Predicting Survival in Idiopathic Pulmonary Fibrosis
Authors: TALMADGE E. KING, JANET A. TOOZE, MARVIN I. SCHWARZ, KEVIN R. BROWN, REUBEN M. CHERNIACK
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Our purpose was to identify clinical, radiological and physiological (CRP) determinants of survival and to develop a CRP scoring system that predicts survival in newly diagnosed cases of idiopathic pulmonary fibrosis (IPF). The study population consisted of 238 patients with biopsy confirmed usual interstitial pneumonia. For each patient, clinical manifestations, chest radiographs, and pulmonary physiology were prospectively assessed. We used Cox proportional-hazards models to assess the effect of these parameters on survival. The effects of age and smoking were included in the analysis. Survival was related to age, smoking status (longer in current smokers), clubbing, the extent of interstitial opacities and presence of pulmonary hypertension on the chest radiograph, reduced lung volume, and abnormal gas exchange during maximal exercise. A mathematical CRP score for predicting survival was derived from these parameters. We showed that this CRP score correlated with the extent and severity of the important histopathologic features of IPF, i.e., fibrosis, cellularity, the granulation/connective tissue deposition, and the total pathologic derangement. Using these models, clinicians are in a better position to provide prognostic information to patients with IPF and to improve the selection of the most appropriate patients for lung transplantation or other standard or novel therapeutic interventions.
A phase I-II study of intensive-dose adriamycin for advanced breast cancer.
Authors: R B Jones, J F Holland, S Bhardwaj, L Norton, C Wilfinger, A Strashun
Journal: Journal of Clinical Oncology (1987)

Twenty-six women with metastatic breast cancer were treated with intensive Adriamycin (Adria Laboratories, Columbus, OH) as a single agent administered for three successive days once a month. Dosing started at 25 or 30 mg/m2/d three times, and was escalated by 5 mg/m2/d monthly to maximal tolerance based on hematologic, mucosal, or cardiac toxicities. Four patients (15%) had complete remissions (CRs) pathologically proven, and six others (23%) sustained complete CRs, but were found to have microscopic residual tumor (three) or refused biopsy (three). Twelve patients (46%) attained partial remission (PR). The overall response (85%) and CR rates (38%) were approximately double those reported with conventional Adriamycin doses. Median unmaintained remission duration for the ten patients in CR was 11 months. Cardiotoxicity, determined by radionuclide physiologic studies, occurred in 16 patients at a mean dose of 459 mg/m2; three patients developed reversible congestive failure. There were no toxic deaths. The median overall survival was 18 months. These data suggest that there is steep dose responsiveness to Adriamycin in metastatic breast cancer, and that more effective techniques for using Adriamycin may exist than those conventionally used.
Postural balance in chronic obstructive pulmonary disease during an acute exacerbation: A comparison with stable participants and healthy controls
Authors: Cristino Oliveira, Annemarie Lee, Louis Irving, Ross Clark, Michelle Thompson, Sandy Clarke, Tamara Baker, Linda Denehy
Journal: European Respiratory Journal (2014)

Background: Impaired balance is evident in people with chronic obstructive pulmonary disease (COPD) compared to the healthy elderly, and specific balance components may be further affected during an acute exacerbation (AECOPD).  Aims: To evaluate balance performance during an AECOPD compared to stable COPD and controls; to identify possible associations between balance measures, dyspnoea, and muscle strength.  Methods: Twenty-six hospitalised patients with AECOPD (FEV 1 , 48±11 %pred) were evaluated prior to discharge using clinical balance tests and centre of pressure analyses, using the Nintendo Wii® balance board. Results were compared to 41 participants with stable COPD (FEV 1 , 45±16 %pred) and 25 matched healthy controls. Dyspnoea was assessed using the Medical Research Council scale and quadriceps strength measured by hand-held dynamometry. Mixed model analysis, paired t-test and regression were used.  Results: Patients with AECOPD presented an impaired performance on anteroposterior displacement of centre of pressure (dAP) on both flat (3.9±1.2 vs 3.3±1.0 vs 2.8±0.6, p≤.01) and foam surfaces (7.0±2.2 vs 5.9±1.7 vs 4.6v1.2, p≤.02), compared with both stable and healthy elderly groups. Increased dyspnoea score and lower quadriceps strength were independently associated with a larger dAP amplitude (pl.03), and explained 40% of dAP variance during AECOPD.  Conclusion: Patients with AECOPD have poorer balance, especially in the forward/backward direction compared with stable COPD and healthy controls; increased dyspnoea and lower muscle strength were associated with the poorer balance performance.
Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency
Authors: Angela Brooks-Wilson, Michel Marcil, Susanne M. Clee, Lin-Hua Zhang, Kirsten Roomp, Marjel van Dam, Lu Yu, Carl Brewer, Jennifer A. Collins, Henri O.F. Molhuizen, Odell Loubser, B.F. Francis Ouelette, Keith Fichter, Katherine J.D. Ashbourne-Excoffon, Christoph W. Sensen, Stephen Scherer, Stephanie Mott, Maxime Denis, Duane Martindale, Jiri Frohlich, Kenneth Morgan, Ben Koop, Simon Pimstone, John J.P. Kastelein, Jacques Genest, Michael R. Hayden
Journal: Nature Genetics (1999)
S0221: Comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer.
Authors: G. Thomas Budd, William E. Barlow, Halle C. F. Moore, Timothy J. Hobday, James A. Stewart, Claudine Isaacs, Muhammad Salim, Jonathan K. Cho, Kristine Rinn, Kathy S. Albain, Helen K. Chew, Gary Von Burton, Timothy David Moore, Gordan Srkalovic, Bradley Alexander McGregor, Lawrence E. Flaherty, Robert B. Livingston, Danika Lew, Julie Gralow, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2013)

CRA1008 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Towards the Effective use of Diagnostic Radiology in Surgical Practice: Discussion Paper
Authors: C J Roberts
Journal: Journal of the Royal Society of Medicine (1983)

This paper takes as an example of the cycle of evaluation the work of the Royal College of Radiologists in connection with the more effective use of preoperative chest X-ray. The work covers a six year period beginning with an observation of practice on a national sample in 1976, progressing to the comparison of existing practice with expectations in 1978. This was followed by the development of guidelines of practice which were disseminated informally, and formally through scientific papers and meetings from 1979. In 1981, practice was again observed in a pilot area to ascertain if the proposed guidelines had produced the desired affect. The results of this second review showed that the intentions of the guidelines had been achieved successfully, i.e. substantial reduction in utilization with considerable potential financial saving without any decrease in the original effectiveness or safety of the intervention. Thus this example shows the closing of the evaluation loop and the successful implementation of change.
Exocrine and Endocrine Testicular Function in Patients with Unilateral Testicular Disease
Authors: K Scheiber, H Marberger, G Bartsch
Journal: Journal of the Royal Society of Medicine (1983)

Amongst 30 patients who had undergone untwisting and fixation for unilateral torsion of the testis, seminal analyses were normal in 15, equivocal in 3 and pathological in 12; and of 46 men with cryptorchidism who had had unilateral orchidopexy, seminal analyses were normal in 13, equivocal in 23 and pathological in 10. Follicle-stimulating hormone levels were found to be elevated in those with equivocal and pathological seminal analyses in both groups. Assessment of testicular function before orchidectomy in 36 patients with seminomas and non-seminomatous testicular tumours revealed only one (with a HCG-negative seminoma) with a normal seminal analysis. Men with HCG-positive testicular tumours were found to have decreased follicle-stimulating hormone levels and elevated 17-beta-oestradiol and prolactin levels.
MCP-3 in inflammatory bowel disease Reply
Authors: U HELWIG
Journal: Gut (2000)

DiVerential expression of cyclooxygenase 2 in human colorectal cancerEDITOR,-We were puzzled by the recent paper by Dimberg and colleagues (Gut 1999;45:730-732) which reported that upregulation of cyclooxygenase 2 (COX-2) protein expression was prominent in rectal adenocarcinomas compared with that in adenocarcinomas arising from the colon."Low or undetectable levels of COX-2 protein expression" were demonstrated in 15 of 19 colonic adenocarcinomas located proximal to the rectum.Overall, upregulation of COX-2 protein expression was reported in only 56% of colorectal cancers.Previous reports, 1-7 which include one by the current authors on a not dissimilar case series, 1 and two in the joint authorship of the accompanying commentary writer, 2 3 have shown consistent upregulation of COX-2 expression in colonic and rectal adenocarcinomas (in 85-90% of cases) compared with matched normal colonic mucosa using diVerent techniques, including northern blot analysis, RT-PCR, western blot analysis, and immunohistochemistry. Furthermore, four of these studies refer to the distribution of adenocarcinomas throughout the colon without showing evidence of diVerential COX-2 expression between rectal and more proximal tumours. 1 2 4 5 In the one previous study which analysed COX-2 protein expression in human colorectal cancers by western blot analysis, 7 immunoreactive COX-2 was detected in 76% of cases with a 10-fold increase in median tissue COX-2 concentration compared with normal colonic mucosa.In our view, the authors should attempt to explain the discrepancy between their results and previously published data.It is interesting to note that, in the study of Kargman et al, five of six patients taking NSAIDs had low or undetectable COX-2 protein expression. 7Moreover, aspirin has recently been shown to suppress induction of COX-2 mRNA and protein in interleukin-1 and phorbol ester stimulated human endothelial cells and fibroblasts. 8Do the authors have data on NSAID use in their cohort of patients prior to surgery?
The role of clinical history and investigations in the diagnosis and exclusion of tuberculosis
Authors: William Ricketts, Elan Tsarfati
Journal: European Respiratory Journal (2013)

Introduction:  Due to the limited sensitivity of definitive tests coupled with slow culture tuberculosis (TB) remains a clinical diagnosis, at least initially in those without sputum smear-positive disease. NICE guidance (2011) provides data on the role of clinical factors in diagnosis, but limited additional data on the role of investigations. We aimed to corroborate this data and investigate the additive effect of different tests and we investigate whether negative predictive values (NPV’s) can exclude TB. Our study was performed in a UK hospital serving a population with an annual TB incidence of ∼60/100,000.  Methods:  235 patients referred to TB clinic had history and investigations recorded in binary form i.e. present/absent or normal/abnormal. Of these 28 were diagnosed with active TB, the remainder with an alternative diagnosis.  Sensitivity, specificity, positive predictive values (PPV’s), NPV’s and odds ratios were calculated using standard formulae for cough, fever, night sweats, weight loss, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white cell count (WCC), globulin, QuantiFERON and Mantoux.  Results:  Results are summarised in Table 1.  Conclusions:  Our data suggest that in the diagnosis of TB history is less important than investigations. However, as 15 (53.6%) of our diagnoses were clinical, with no laboratory confirmation our results may be a factor of clinician over reliance on investigations.
Further Observations on the Inhibition of Tumor Growth by Corynebacterium parvum with Cyclophosphamide. III. Effect of C. parvum on Cyclophosphamide Metabolism2
Authors: Bernard Fisher, Norman Wolmark, Herbert Rubin
Journal: JNCI Journal of the National Cancer Institute (1976)

Results of investigations employing [14C]cyclophosphamide (CY) demonstrated that even though total plasma radioactivity was similar in female C3HeB/FeJ mice treated either with CY alone or Corynebacterium parvum and CY, the proportion of total activity due to non metabolized CY was greater when C. parvum was used. These findings indicated that the anti-tumor effect of C. parvum may not have been entirely due to its immunopotentiating properties but may also have been related to its effect on the metabolism of CY.
Multimodal therapy for the management of localized Ewing's sarcoma of pelvic and sacral bones: a report from the second intergroup study.
Authors: R G Evans, M E Nesbit, E A Gehan, L A Garnsey, O Burgert, T J Vietti, A Cangir, M Tefft, P Thomas, F B Askin
Journal: Journal of Clinical Oncology (1991)

A total of 59 eligible patients with localized Ewing's sarcoma of the pelvic and sacral bones were entered into a multimodal Intergroup Ewing's Sarcoma Study (IESS-II) (1978 to 1982) and compared with a historical control series of 68 patients entered into an earlier multimodal Intergroup Ewing's Sarcoma Study (IESS-I) (1973 to 1978). High-dose intermittent multiagent chemotherapy (vincristine, cyclophosphamide, Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], and dactinomycin) was given to all patients for 6 weeks before and for 70 weeks following local therapy. All patients who had a tumor biopsy or incomplete resection performed received a dose of 55 Gy to the tumor bed. With a median follow-up time of 5.5 years, two of 59 patients (3%) had a local recurrence, five patients (8%) had a local recurrence and metastases, and 17 patients (29%) developed metastases only. There was significant statistical evidence of an advantage in relapse-free survival (RFS) and survival (S) for patients on IESS-II versus IESS-I, P = .006 and P = .002, respectively. At 5 years, the comparison between IESS-II versus IESS-I was 55% versus 23% for RFS and 63% versus 35% for S.
Aberrant intracellular expression of laminin α-2 and -5 in bronchiolar epithelium of COPD patients
Authors: Oskar Johansson, Jonas Erjefält, Leif Bjermer, Claes-Göran Löfdahl, Gunilla Westergren-Thorsson, Oskar Hallgren
Journal: European Respiratory Journal (2014)

Laminins constitute fundamental building blocks of basement membranes and have been shown to influence cell behaviour in a laminin-subunit specific manner. One such example is that immune cell diapedesis is facilitated by laminin α-4 compared to laminin α-5. Although changes in laminin expression have been observed in COPD, more in depth studies is needed to unravel the pathophysiological implications of these alterations. This study aimed to examine the abundance and distribution of specific laminin subunits in COPD. Laminin α-2 and α-5 expression were evaluated with immunohistochemistry in peripheral lung tissue from COPD patients (GOLD I-IV), smoker and non-smoker controls.  Immunoreactivity for laminin α-5 was found in basal membranes underlying bronchiolar epithelium and endothelium in peribronchiolar blood vessels. Bronchiolar epithelium was found to show a prominent intracellular immunoreactivity for laminin α-5 in COPD-afflicted lungs, in stark contrast to control lung epithelium which lacked this immunoreactivity pattern. Intracellular immunoreactivity was restricted to well-delimited subcellular compartments overlying the nucleus on the luminal side of the columnar epithelial cell. Laminin α-2 were not found in basal membranes of neither control nor COPD lung, while showing an intracellular immunoreactivity pattern similar to that of laminin α-5 in the bronchiolar epithelium of COPD-patients.  Our data indicate that COPD pathology is associated with specific changes in expression patterns of laminin α-2 and α-5. Disruption of tissue homeostasis regarding laminin expression might contribute to chronic inflammation and a process of ongoing extracellular matrix remodelling.
Abstract 3379: cGMP Specific Phosphodiesterase Type 5A Activity is Regulated by S-nitrosylation at Cys 181
Authors: Christopher I Murray, Milena A Gebska, Azeb Haile, Manling Zhang, David A Kass, Hunter C Champion, Jennifer E Van Eyk
Journal: Circulation (2008)

Introduction: cGMP specific phosphodiesterase type 5A (PDE5A) has a key role in limiting the effect of the second messenger cGMP as demonstrated by the use of the specific inhibitor, sildenafil. However, the mechanism by which PDE5 activity is regulated is not fully understood. Recently, it has been reported that PDE5A specifically degrades the pool of cGMP produced by the nitric oxide (NO) stimulated soluble guanylate cyclase. NO is known to regulate other proteins in this pathway through S-nitrosylation, a redox modification where an NO group is covalently added to the sulfur atom of a cysteine. Here we test the hypothesis that PDE5 activity is regulated by S-nitrosylation and determine the critical modified cysteine residues. Methods: Rates of cGMP hydrolysis were measured by an in vitro activity assay using purified mouse flag-PDE5 treated with the NO-donor, S-Nitrosoglutathione (GSNO, 1–100μM) or control. The S-nitrosylation status of PDE5A was determined by biotin switch assay of cell lysates over expressing flag-PDE5A using the equivalent conditions. After NO modifications were replaced with biotin moieties, labeled proteins or trypsin digested peptides were captured with streptavidin agarose and evaluated by western blot or tandem mass spectrometry, respectively. Results: PDE5A activity was found to be decreased in a dose dependent manner with NO donor inducing a 25.0 ± 3.8% (n=4, p&lt;0.01) decrease with 100μM GSNO treatment compared to controls. PDE5A was S-nitrosylated by the NO donors in a similar dose dependent manner when analyzed using the biotin switch assay. Subsequent mapping studies identified 2 potential sites of S-nitrosylation at C181 and C210, both of which are located in the N-terminal regulatory domain. Independent mutation of candidate cysteines to serine residues revealed that C181 is more receptive to NO modification than C210. Additionally, the C181S PDE5A was found to be resistant to the NO-donor dependent decrease (0.55 ± 2.3%, p=0.9) in activity while C210S activity was found to be depressed in the presence of 100μM GSNO (28.9 ± 1.7%, p&lt;0.01) (n=4). Conclusions: These data indicates that PDE5A activity is negatively regulated by S-nitrosylaion at C181 which may contribute to the overall regulation of cGMP signaling in the cell. This research has received full or partial funding support from the American Heart Association, AHA Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia &amp; Washington, DC).
Validity of Berlin questionnaire for obstructive sleep apnea in a sleep clinic population
Authors: Sevinc Sarinc Ulasli, Ersin Gunay, Tulay Koyuncu, Olcay Akar, Bilal Halici, Mehmet Unlu
Journal: European Respiratory Journal (2013)

Objective: The Berlin Questionnaire (BQ) and Epworth Sleepiness Scale (ESS) are two of the widely used screening instruments for subjects suffering from sleep disorders. The objective of the present study was to determine the validity of the BQ and ESS in the patients who were admitted to our sleep clinic, using overnight polysomnography as the ‘‘gold standard’’.

Methods: The BQ and ESS were performed to 1375 patients hospitalized in our Sleep Clinic for polysomnographic evaluation between 2009-2013.Patients' demographics and polysomnography results were evaluated. Sensitivity and specificity of BQ and ESS were determined.

Results: One thousand one hundred sixty of the 1375 subjects had apnea-hypopnea index (AHI) > 5 and 71.1% of them were classified as being at high risk of sleep apnea with BQ and 46.6% of them were classified as having high score with ESS. Being in the high-risk group with the self-reported BQ predicted an AHI > 5 with a sensitivity of 0.74 and a specificity of 0.44, versus a sensitivity of 0.48 and a specificity of 0.60 with the self-reported ESS. At a cut-off AHI=15, the BQ had a sensitivity of 0.77 and a specificity of 0.39. AHIs were significantly correlated with the scores in each category and the total scores of BQ (p<0.001).

Conclusions: The BQ is a poor predictor of obstructive sleep apnea in patients admitted to our sleep clinic due to the low specificity levels.
Clinical features of alpha one antitrypsin deficiency in non cystic fibrosis bronchiectasis
Authors: Mohamed Badawy, Atef Farouk, Hamdy Mohammdien
Journal: European Respiratory Journal (2012)

Setting:  It9s important to identify manifestation of alpha1-antitrypsin deficiency (A1ATD) in bronchiectasis to improve patients care and outcome.  Objective:  To clinically evaluate A1ATD in patients with non cystic fibrosis bronchiectasis. Material and methods:  Patients with non cystic fibrosis bronchiectasis were diagnosed clinically and confirmed radiologically. They fulfilled the inclusion criteria and divided into group (A) bronchiectasis with hyperinflation (30cases) and group (B) bronchiectasis without hyperinflation (30 cases). All patients were subjected to history taking, pulmonary function tests, and quantitative measurements of serum A1AT by radio-immunoassay.  Results:  Mean age of both groups was (50±8.58) and (36.87±11.35) respectively (p=0.001). There were significant difference in gender distribution (p=0.006), and smoking history (p=0.001). Heamoptysis presented in 12 cases (40%), and 20 cases (66.67%) in both groups respectively (p=0.04). Dyspnea presented in 27 cases (90%) and 19 cases (63%) for group A&B with (P=0.02). There were no significant difference in sinusitis, hepatological symptoms, clubbing and family history. There were significant difference in cyanosis, oedema of lower limb, wheeze, radiological findings and spirometeric tests (P value 0.01, 0.004, 0.001, 0.001, 0.001) respectively. Three cases (5%) of A1ATD were diagnosed among all patients9 one case (1.5%) in group (A) of MZ allele and two brother cases (3.5%) in group (B) of SZ allele without statistical significance.  Conclusion:  A1ATD is seldom found in patients with bronchiectasis even with concomitant hyperinflation. Inheritance could influence an individual risk of A1ATD for developing bronchiectasis.