tbuckley/cabot-search huggingface dataset:
Relearning an old lesson: stopping trials early
Authors: N. M. Rahman, R. J. O. Davies
Journal: Thorax (2010)

A well designed and delivered clinical trial is the main tool to define whether medical interventions ‘work’, and how well. As such, they are potent weapons in the armoury of medical progress—and like all potent weapons need to be used with care.

In this month's Thorax, Koegelenberg et al ( see page 857 ) report the findings of a trial comparing the diagnostic accuracy of closed pleural biopsy (Abrams needle) and cutting needle pleural biopsy after thoracic ultrasound, for the diagnosis of pleural tuberculosis (TB).1 This question is clearly important given the global significance of TB, and the key role of pleural biopsy in the diagnosis and microbiological assessment of its pleural presentations. To date, there are no published studies assessing ultrasound-guided pleural biopsy for the diagnosis of TB-related pleural effusions. This study is a continuation of this group's research programme which has a track record of delivering valuable evidence in the diagnosis of pleural TB, not least their previous study showing that thoracoscopy is superior to closed pleural biopsy in this disease.2

Their studies are conducted in an area with a high prevalence of TB, with all the recruited subjects receiving the compared diagnostic tests, allowing the comparison of diagnostic results. In this new study, all patients underwent both Abrams biopsy and cutting needle biopsy, performed in random order. The design is simple, logical and efficient, with the diagnostic accuracy for TB assessed against accepted ‘gold standards’. Given the biology of pleural TB, which manifests as diffuse pleural involvement, it is reasonable to propose that …
Recombinant Apolipoprotein A-I <sub>Milano</sub> Dimer Inhibits Carotid Intimal Thickening Induced by Perivascular Manipulation in Rabbits
Authors: Maurizio R. Soma, Elena Donetti, Cinzia Parolini, Cesare R. Sirtori, Remo Fumagalli, Guido Franceschini
Journal: Circulation Research (1995)

Abstract Apolipoprotein A-I Milano (apoA-I M ), a natural variant of apolipoprotein A-I (apoA-I), confers to the carriers a significant protection against vascular disease. The antiatherogenic activity of a recombinant disulfide-linked apoA-I M dimer (rA-I M /A-I M ) was analyzed in vivo by evaluating its effect on neointimal formation induced by periarterial manipulation in 1% cholesterol–fed rabbits. A flexible collar was applied around the carotid artery 21 days after the beginning of the dietary regimen, and animals were killed 10 days later. Rabbits were injected five times with reconstituted high-density lipoprotein containing egg phosphatidylcholine (EPC) and rA-I M /A-I M (119 mg EPC+40 mg protein per dose) or with EPC liposomes (119 mg EPC per dose) beginning either 5 days before or at the day of collar positioning. Neither treatment affected plasma cholesterol levels. A significant intimal thickening was observed in control animals; the intima-to-media (I/M) ratio was 0.63±0.11 versus 0.03±0.05 for the sham-operated contralateral arteries. Neointimal formation was markedly inhibited in animals pretreated with rA-I M /A-I M before lesion induction (I/M, 0.26±0.19) but not in those in which treatment began the day of collar insertion (I/M, 0.74±0.14). EPC liposomes did not affect neointimal formation (I/M, 0.50±0.14 and 0.51±0.07 in the two treatment groups). Proliferation of smooth muscle cells, assessed by direct incorporation of bromo-2′-deoxyuridine (BrdU) into replicating DNA, was reduced by ≈30% and 75% in the intimal and medial tissues of rA-I M /A-I M –pretreated rabbits. Thus, a short-term treatment with rA-I M /A-I M inhibits smooth muscle cell proliferation and intimal thickening in rabbits, providing evidence for the potential use of rA-I M /A-I M in the treatment of atherosclerosis.
Electrical impedance measured to five skin depths in mild irritant dermatitis induced by sodium lauryl sulphate
Authors: I. NICANDER, S. OLLMAR, B.LUNDH ROZELL, A. EEK, L. EMTESTAM
Journal: British Journal of Dermatology (2006)

The non-invasive electrical impedance technique used in this study reflects structural changes in a tissue, and provides an estimate of the level of oedema by a simple impedance index. Sodium lauryl sulphate (SLS), dissolved in water at concentrations of 0.1, 0.5 and 2.0%, was applied for 24 h in 12 mm Finn chambers on both volar forearms of 12 healthy volunteers. An unoccluded area was used as a reference site. Readings from all sites were taken before the application of the irritant, and 24 h after its removal. After the last reading, a 3-mm punch biopsy was taken from each test site for histological examination. The results obtained from electrical impedance measurements at five different skin depths were correlated with those obtained from histological examination, visual scoring and transepidermal water loss (TEWL). For all of the methods used the responses were proportional to the concentration of the irritant. Statistically significant changes of electrical impedance were found for all depths and concentrations, except for 0.1% SLS at the most superficial depth. The histological changes were focused in the epidermis, and mainly consisted of oedema. Alterations in the thickness of the epidermis due to oedema were used as a quantitative parameter for correlation with the assessment of irritation using the electrical impedance technique. For the detection of irritant reactions, TEWL and electrical impedance are more sensitive than visual scoring, and selection of the optimum depth penetration further increases the sensitivity of the electrical impedance measurement.
Molecular Imaging of Matrix Metalloproteinase in Atherosclerotic Lesions
Authors: Shinichiro Fujimoto, Dagmar Hartung, Satoru Ohshima, D. Scott Edwards, Jun Zhou, Padmaja Yalamanchili, Michael Azure, Ai Fujimoto, Satoshi Isobe, Yuji Matsumoto, Hendricus Boersma, Nathan Wong, Junichi Yamazaki, Navneet Narula, Artiom Petrov, Jagat Narula
Journal: Journal of the American College of Cardiology (2008)
Circulating dihydrotestosterone may not reflect peripheral formation.
Authors: V Toscano, R Horton
Journal: Journal of Clinical Investigation (1987)

We compared the blood (PBDHT) and urine (PUDHT) production rate of dihydrotestosterone (DHT) in normal men and women to determine whether peripheral formation was totally reflected in blood. PBDHT was similar when measured at both sites in men (674 +/- 79 vs. 788 +/- 207 SE micrograms/d); however, PUDHT was greater than PBDHT in women (174 +/- 55 vs. 55 +/- 8 micrograms/d, P less than 0.02). Excretion rates of DHT and 3 alpha-androstanediol (3 alpha diol) were similar in both sexes despite major differences in blood levels. However, between sexes large differences were present in 3 alpha diol glucuronide (3 alpha diolG) in both plasma and urine. These observations indicate that peripheral (renal) formation of DHT and probably 3 alpha diol were not accurately determined by measurement of these steroids in blood. The large difference between blood and urine production rates in women suggests an important role of non-testosterone precursors of 5 alpha-reduced steroids. Measurements of 3 alpha diolG may provide more insight into these peripheral events.
Gene Profiling in Atherosclerosis Reveals a Key Role for Small Inducible Cytokines
Authors: Esther Lutgens, Birgit Faber, Kitty Schapira, Chris T.A. Evelo, Rachel van Haaften, Sylvia Heeneman, Kitty B.J.M. Cleutjens, Ann Pascale Bijnens, Linda Beckers, J. Gordon Porter, Charles R. Mackay, Paul Rennert, Veronique Bailly, Matthew Jarpe, Brian Dolinski, Victor Koteliansky, Tony de Fougerolles, Mat J.A.P. Daemen
Journal: Circulation (2005)

Pathological aspects of atherosclerosis are well described, but gene profiles during atherosclerotic plaque progression are largely unidentified.Microarray analysis was performed on mRNA of aortic arches of ApoE-/- mice fed normal chow (NC group) or Western-type diet (WD group) for 3, 4.5, and 6 months. Of 10 176 reporters, 387 were differentially (>2x) expressed in at least 1 group compared with a common reference (ApoE-/-, 3- month NC group). The number of differentially expressed genes increased during plaque progression. Time-related expression clustering and functional grouping of differentially expressed genes suggested important functions for genes involved in inflammation (especially the small inducible cytokines monocyte chemoattractant protein [MCP]-1, MCP-5, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, MIP-2, and fractalkine) and matrix degradation (cathepsin-S, matrix metalloproteinase-2/12). Validation experiments focused on the gene cluster of small inducible cytokines. Real-time polymerase chain reaction revealed a plaque progression-dependent increase in mRNA levels of MCP-1, MCP-5, MIP-1alpha, and MIP-1beta. ELISA for MCP-1 and MCP-5 showed similar results. Immunohistochemistry for MCP-1, MCP-5, and MIP-1alpha located their expression to plaque macrophages. An inhibiting antibody for MCP-1 and MCP-5 (11K2) was designed and administered to ApoE-/- mice for 12 weeks starting at the age of 5 or 17 weeks. 11K2 treatment reduced plaque area and macrophage and CD45+ cell content and increased collagen content, thereby inducing a stable plaque phenotype.Gene profiling of atherosclerotic plaque progression in ApoE-/- mice revealed upregulation of the gene cluster of small inducible cytokines. Further expression and in vivo validation studies showed that this gene cluster mediates plaque progression and stability.
Arterial Stiffness Is Associated With Incident Albuminuria and Decreased Glomerular Filtration Rate in Type 2 Diabetic Patients
Authors: Ryotaro Bouchi, Tetsuya Babazono, Michino Mugishima, Naoshi Yoshida, Izumi Nyumura, Kiwako Toya, Ko Hanai, Nobue Tanaka, Akiko Ishii, Yasuko Uchigata, Yasuhiko Iwamoto
Journal: Diabetes Care (2011)

OBJECTIVE To investigate the association between aortic stiffness and incident albuminuria and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We investigated 461 Japanese type 2 diabetic patients, comprising 199 women and 262 men, with a mean age of 59 ± 11 years. Patients were divided into two groups according to the median value of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness. The end point was defined as the transition from normo- to microalbuminuria or micro- to macroalbuminuria. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI. The correlation between cf-PWV and rate of change in eGFR was also determined by linear regression analysis. RESULTS The baseline mean (± SD) cf-PWV was 9.6 ± 2.4 m/s. During a median follow-up period of 5.9 years (range 0.3–8.6), progression of albuminuria was observed in 85 patients. The 5-year cumulative incidence of the end point in patients with cf-PWV below and above the median was 8.5 and 19.4%, respectively (P = 0.002, log-rank test). cf-PWV was significantly associated with incident albuminuria (HR 1.23, 95% CI 1.13–1.33, P &amp;lt; 0.001) by multivariate Cox regression analysis. A significant association between cf-PWV and annual change in eGFR was also suggested by multiple linear regression analysis (standardized estimate −0.095, P = 0.031). CONCLUSIONS Aortic stiffness is associated with incident albuminuria and the rate of decline in glomerular filtration rate in type 2 diabetic patients.
Pressure-Flow Relations in Dog Arteries
Authors: E. O. ATTINGER, H. SUGAWARA, A. NAVARRO, A. RICCETTO, R. MARTIN
Journal: Circulation Research (1966)

The propagation of the arterial pressure and flow pulses through the vascular beds is characterized by marked changes in shape and magnitude. In order to understand better the mechanisms which account for these changes, instantaneous pressures and flows were measured simultaneously at various sites in the arterial tree of 12 anesthetized dogs, using Statham strain gauges and electromagnetic flowmeters. The data were processed by on-line Fourier analysis and the frequency spectra of pressure, flow and vascular impedance at these sites were evaluated. In these dogs about 10% of the cardiac output was distributed to the head, 14% to the kidney, 35% to the gastrointestinal tract, 14% to the pelvic organs and 6% to the legs. The input impedances of the various beds were frequency dependent, the frequency-dependent components varying between 2 and 45% of the corresponding D-C impedances (peripheral vascular resistance). The viscous losses associated with pulsatile flow were larger than those for corresponding steady flows. The excess losses varied between 9 and 30% of the mean flow losses. The marked decrease in cross section down the aorta lead to considerable acceleration of the mean blood velocity and corresponding pressure losses despite the drainage through aortic branches. Comparisons of measured flows with those predicted from Womersley's theory showed satisfactory agreement for short vascular segments. However the theory underestimates the losses occurring in the nonuniform arterial tree. On the basis of anatomic measurements, the space dependence of resistance, inertance and vascular distensibility was evaluated.
Choosing the Best Trastuzumab-Based Adjuvant Chemotherapy Regimen: Should We Abandon Anthracyclines?
Authors: Harold J. Burstein, Martine J. Piccart-Gebhart, Edith A. Perez, Gabriel N. Hortobagyi, Norman Wolmark, Kathy S. Albain, Larry Norton, Eric P. Winer, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2012)

Harold J. Burstein, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Martine J. Piccart-Gebhart, Institut Jules Bordet, Brussels, Belgium Edith A. Perez, Mayo Clinic, Jacksonville, FL Gabriel N. Hortobagyi, MD Anderson Cancer Center, Houston, TX Norman Wolmark, Allegheny General Hospital, National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA Kathy S. Albain, Loyola University Chicago Stritch School of Medicine, Maywood, IL Larry Norton, Memorial Sloan-Kettering Cancer Center, New York, NY Eric P. Winer, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY
Potential Utility of BimS as a Novel Apoptotic Therapeutic Molecule
Authors: Kenneth W. Yip, Anna Li, Jian-Hua Li, Wei Shi, Marie C. Chia, Shahnaz Al Rashid, Joseph D. Mocanu, Alexander V. Louie, Otto Sanchez, Dolly Huang, Pierre Busson, Wen-Chen Yeh, Ralph Gilbert, Brian O'sullivan, Patrick Gullane, Fei-Fei Liu
Journal: Molecular Therapy (2004)

We have previously demonstrated a 1000-fold induction of gene expression exclusive to Epstein–Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) cells using an adenoviral vector (ad5.oriP). This platform allows us to explore tumor-specific gene therapy with BimS (ad5.oriP.BimS), a potent proapoptotic Bcl-2 family member. Ad5.oriP.BimS (25 infectious units (ifu)/cell) reduced C666-1 viability in a time- and dose-dependent manner to 15% survival. The effect was enhanced with radiation (6 Gy). Three days after infection, the proportion of apoptotic cells increased from 3.5% (control) to 47.5% (25 ifu/cell). Confocal microscopy demonstrated Bim colocalization to the mitochondria within 18 h of ad5.oriP.BimS infection. Ad5.oriP.BimS induced a 2.8-, 2.1-, and 1.85-fold increase in caspase-3, -8, and -9 activities, respectively. When C666-1 cells were infected with ad5.oriP.BimS (20 ifu/cell), no tumors formed in 7/9 mice followed for 100 days. Six intratumoral injections of ad5.oriP.BimS (1.5 × 109 ifu/dose) in combination with radiation were sufficient to cause almost complete disappearance of established C666-1 or C15 xenograft tumors. Intravenous injections of ad5.oriP.BimS (109 ifu) induced mild perturbation in liver function tests, associated with hepatocyte apoptoses and mitoses. This vector appears to be safe and effectively cytotoxic to EBV-positive NPC cells both in vitro and in vivo, mediated primarily through the induction of apoptosis.
Sporotrichosis as a presenting manifestation of hairy cell leukemia
Authors: Shimareet Kumar, Dhruv Kumar, William K. Gourley, Jack B. Alperin
Journal: American Journal of Hematology (1994)

Abstract An infectious episode is the presenting manifestation of hairy cell leukemia (HCL) in approximately 30% of cases. Most often this is bacterial and only rare cases of opportunistic fungal infection are described. We report a patient who presented with sporotrichal involvement of multiple cutaneous sites and lymph nodes. The lesions resolved following antifungal therapy, but persisting pancytopenia and splenomegaly necessitated further hematological evaluation. A diagnosis of HCL was suspected based on morphologically characteristic hairy cells in the peripheral blood that contained tartrate resistant acid phosphatase. A bone marrow biopsy specimen had a normocellular marrow with an increase in interstitial lymphoid cells that stained with L26, MB2, and LN2 antibodies. On flow cytometry these cells were positive for the leukocyte common antigen, B cell markers, and the CD11c antigen confirming the diagnosis of HCL. We believe that this is the first report of sporotrichosis infection as a presenting manifestation of HCL. © 1994 Wiley‐Liss, Inc.
Differential diagnosis and management of focal ground-glass opacities
Authors: M. Infante, R. F. Lutman, S. Imparato, M. Di Rocco, G. L. Ceresoli, V. Torri, E. Morenghi, F. Minuti, S. Cavuto, E. Bottoni, F. Inzirillo, U. Cariboni, V. Errico, M. A. Incarbone, G. Ferraroli, G. Brambilla, M. Alloisio, G. Ravasi
Journal: European Respiratory Journal (2008)

Focal pulmonary ground-glass opacities (GGOs) can be associated with bronchioloalveolar carcinoma. The present retrospective study aimed to test the validity of a multistep approach to discriminate malignant from benign localised (focal) GGOs, identifies useful diagnostic features on computed tomography (CT), and suggests appropriate management guidelines. A stepwise approach, including oral antibiotics, follow-up high-resolution CT (HRCT) 40-60 days later and CT-guided core biopsy, was used. All cases with localised GGOs detected since 2001 were reviewed. CT features were described according to a structured scheme. In total, 40 patients were evaluated. Of these, 11 patients were diagnosed with benign GGOs, 19 patients had lung cancer and 10 were undetermined. Nonpolygonal shape, apparent radial growth and clear-cut margins were associated with a malignant histology. The specificity of CT findings was low. Diagnostic accuracy increased after oral antibiotics, follow-up HRCT and percutaneous core biopsy. Overall, 18 patients underwent surgery for lung cancer. In conclusion, malignant ground-glass opacities have a fairly typical appearance, but some benign lesions closely mimic their malignant counterparts. The stepwise approach adopted in the present study increased the diagnostic specificity and reduced time to definitive diagnosis. Segmentectomy might be the ideal resection volume for such tumours.
Conditional Probability Program for Diagnosis of Thyroid Function
Authors: John E. Overall
Journal: JAMA (1963)

The frequencies of occurrence of certain clinical findings (signs, symptoms, and laboratory data) were determined in 879 patients who had been classified as hypothyroid, euthyroid, or hyperthyroid on the basis of their responses to therapy during at least 6 mo of observation. A Bayesian conditional probability model was employed to estimate the probability of each of these three conditions for each possible combination of clinical findings. When the study was limited to 268 cases in which the data were considered reasonably complete, the computer program gave the correct classification (ie, successfully predicted the therapeutic result) in 258 (96%). This degree of accuracy approached the level of agreement to be expected between an expert consultant and a well-qualified diagnosing physician.
Functional assessment of the hand: reproducibility, acceptability, and utility of a new system for measuring strength.
Authors: P Helliwell, A Howe, V Wright
Journal: Annals of the Rheumatic Diseases (1987)

A new system for measuring strength of the hand using a torsion dynamometer linked to a microprocessor is described. The system permits analysis of timed squeezes of both grip and pinch and is adjustable to all sizes of hand and degrees of hand deformity. Results obtained with the system were found to be reproducible, and the rigid device was acceptable to a group of patients with arthritic hands. In rheumatoid arthritis there is a marked reduction in maximum grip and pinch strength, together with a prolongation of the time taken to reach this maximum, and increased fatigue. The limitations of grip strength as a measure of function of the hand are discussed.
Uromodulin Levels Associate with a Common UMOD Variant and Risk for Incident CKD
Authors: Anna Köttgen, Shih-Jen Hwang, Martin G. Larson, Jennifer E. Van Eyk, Qin Fu, Emelia J. Benjamin, Abbas Dehghan, Nicole L. Glazer, W.H. Linda Kao, Tamara B. Harris, Vilmundur Gudnason, Michael G. Shlipak, Qiong Yang, Josef Coresh, Daniel Levy, Caroline S. Fox
Journal: Journal of the American Society of Nephrology (2009)

Common variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein), associate with chronic kidney disease (CKD) and estimated GFR (eGFR). Whether uromodulin levels associate with UMOD variants or with the risk for developing CKD is unknown. We conducted an age- and gender-matched case-control study (n = 200) of incident CKD (eGFR <60 ml/min per 1.73 m2) within the Framingham Heart Study (FHS). Baseline urinary uromodulin concentrations were related to case-control status 9.9 yr later and to genotype at rs4293393. As a replication set, we tested the genotype association with uromodulin concentration in the Atherosclerosis Risk in Communities (ARIC) Study (n = 42). Geometric means of uromodulin concentrations were 51% higher in case than in control subjects (P = 0.016). The adjusted odds ratio of CKD per 1-SD higher concentration of uromodulin was 1.72 (95% confidence interval 1.07 to 2.77; P = 0.03) after accounting for CKD risk factors and baseline eGFR. We observed lower urinary uromodulin concentrations per each copy of the C allele at rs4293393 in both cohorts. In summary, elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region.
Effect of travelling to 2590m on 6-minute walk distance, blood gases and symptoms of acute mountain sickness in COPD patients
Authors: Tsogyal Daniela Latshang, Michael Furian, Deborah Flück, Sebastian Daniel Segitz, Christian Murer, Philipp Scheiwiller, Séverine Mueller-Mottet, Batyr Osmonov, Silke M. Kueest, Adrian Steiner, Silvia Ulrich, Thomas Rothe, Sara E. Hartmann, Marc J. Poulin, Malcolm Kohler, Konrad E. Bloch
Journal: European Respiratory Journal (2014)

Introduction   The aim of the current study was to evaluate the exercise performance and health effects of altitude travel in patients with COPD.   Methods   40 COPD patients, GOLD 2-3, living at    Results   On the first morning at 2590m, patients perceived mild symptoms of acute mountain sickness, 5 required nocturnal oxygen because of discomfort or severe hypoxemia. They were able to remain at altitude and felt well thereafter. One patient refused to ascend to 2590m because of insomnia at 1650m. Compared to 490m, the 6-MWD at altitude was reduced, arterial oxygen saturation, pO2 and pCO2 were decreased.   Conclusions   Travelling to 2590m was well tolerated by lowlanders with COPD, GOLD grade 2-3. None required an unscheduled descent. However, some suffered from mild symptoms of acute mountain sickness or required nocturnal oxygen. The stay at moderate altitude was associated with a reduced 6-MWD and hypoxemia.  Grant: Swiss National Science Foundation, Zurich Lung League.