tbuckley/cabot-search huggingface dataset:
Tranylcypromine Versus Venlafaxine Plus Mirtazapine Following Three Failed Antidepressant Medication Trials for Depression: A STAR*D Report
Authors: Patrick J. McGrath, Jonathan W. Stewart, Maurizio Fava, Madhukar H. Trivedi, Stephen R. Wisniewski, Andrew A. Nierenberg, Michael E. Thase, Lori Davis, Melanie M. Biggs, Kathy Shores-Wilson, James F. Luther, George Niederehe, Diane Warden, A. John Rush
Journal: American Journal of Psychiatry (2006)

Objective: The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials. Method: Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine (N=51). The primary outcome measure was whether patients achieved remission, which was defined as a score ≤7 at exit on the 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D was administered by telephone by raters to whom treatment was masked. Results: Remission rates were not significantly different between the two treatment groups (6.9% for the tranylcypromine group and 13.7% for the venlafaxine plus mirtazapine group). The mean daily dose at exit for tranylcypromine was 36.9 mg (SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and for mirtazapine, 35.7 mg (SD=17.6). Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance. Conclusions: Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments.
India plans to audit clinical trials
Authors: Ganapati Mudur
Journal: BMJ (2005)

The Indian government has announced a plan to set up a registry and to audit some clinical trials after being dogged for years by controversies over illegal and unethical trials.

The Indian Council of Medical Research will establish a registry of clinical trials conducted in the country, and drug regulators will scrutinise trials to ensure compliance with ethical guidelines and good clinical practice, officials said last week.

The health ministry has begun training drug inspectors to audit trials, Ashwini Kumar, …
Glucose Variability and Complications
Authors: Geremia B. Bolli
Journal: Diabetes Care (2006)

In this issue of the Diabetes Care , Kilpatrick et al. (1) report their analysis of the large Diabetes Control and Complications Trial (DCCT) database on the relationship between glucose variability and relative risk of developing microangiopathic complications in type 1 diabetes. They find that glucose variability (intraday blood glucose excursions) does not play a role and conclude that only elevation of mean blood glucose over time (as expressed by its integrated measure over the previous ∼8 weeks’ A1C) associates with proportionally greater risk of developing microangiopathy long term.

This result translates into an important, practical message for subjects with type 1 diabetes and people delivering diabetes care (doctors, nurses, educators, dietitians, etc.). Consider the following example: two young subjects with newly diagnosed type 1 diabetes initiate intensive insulin treatment and are both able to maintain similar A1C <7.0% over the years. However, one subject exibits minor intraday excursions in blood glucose, whereas the other has large peaks of hyperglycemia, for example after meals, but still maintains A1C <7.0% by compensatory prolonged plateaus of low blood glucose between meals. According to the results of Kilpatrick et al., the latter subject with elevated variability in intraday blood glucose, but A1C <7.0%, has no additional risk of developing microangiopathic complications compared with the former subject with greater stability of blood glucose and similar A1C. This conclusion indicated by the study of Kilpatrick et al. deserves some comments.

First, the conclusion is unexpected. The current, prevalent hypothesis based on in vitro data is that glucose variability might play an important role in the risk for long-term microangiopathic complications of type 1 diabetes (2). According to this view (2), intraday glucose variability would explain the epidemiological observation of the DCCT of greater risk for retinopathy progression in the conventional compared with intensive treatment when …
Aberrant serum hyaluronan and hyaluronidase levels in scleroderma
Authors: B.A. Neudecker, R. Stern, M.K. Connolly
Journal: British Journal of Dermatology (2004)

Background Scleroderma, or systemic sclerosis, is characterized by aberrations of extracellular matrix deposition. These changes parallel early stages of wound healing when increased deposition of hyaluronan (HA) and collagen occur. Both processes result ultimately in the formation of fibrotic scar tissue. Activities of HA synthase and hyaluronidase, the enzymes that synthesize and degrade HA, are critical in HA turnover. Both become elevated whenever increased matrix deposition occurs. HA deposition occurs early in wound healing, and increases are documented in the circulation of scleroderma patients. We postulated that elevated HA and hyaluronidase may both be indicators of early-stage disease in scleroderma, in parallel with early changes observed in wound healing. In an attempt to reduce HA accumulation and the associated fibrosis in scleroderma tissues, topical and intravenous hyaluronidase administrations have been used in the past as treatment modalities, with occasional success. This also suggested that hyaluronidase enzyme activity is involved in the disease process. It is now recognized that the hyaluronidases constitute an enzyme family. The somatic hyaluronidase Hyal-1 is the only activity present in human serum. Objectives To determine levels of HA and Hyal-1 in the sera of scleroderma patients at various stages of their disease. Methods Levels of HA and Hyal-1 activity were determined in 25 scleroderma patients. Subjects were separated into two groups, those in the early stage with duration of disease of 2 years or less, and late-stage patients with disease duration of more than 2 years. Results In early-stage scleroderma, levels of HA were elevated significantly, as predicted, in comparison with late-stage patients and controls. Late-stage levels of HA were comparable with those found in control sera. By contrast, levels of Hyal-1 activity were normal in early-stage patients, similar to those in controls, but were decreased in late-stage patients, falling even below those of controls. Conclusions We have confirmed that circulating levels of HA are elevated in scleroderma, but show for the first time that such elevations occur predominantly in early-stage disease. Patients with late-stage disease have decreased serum Hyal-1 activity, perhaps reflecting decreased levels of HA turnover. This study also represents the first time that hyaluronidase activity levels have been determined in scleroderma patients.
PASSIVE TRANSFER OF LYMPHOCYTES FROM DIABETIC MAN TO ATHYMIC MOUSE
Authors: J Lipsick, G Beattie, A.G Osler, N.O Kaplan, O Thurneyssen, F.K Jansen, B Vialettes, PH Vague, J.L Selam, J Mirouze, A.Sitges Serra, J.R Farndon, B.K Shenton, IvanD.A Johnston
Journal: The Lancet (1979)
Linear endobronchial ultrasonography: a novelty turned necessity for mediastinal nodal assessment
Authors: Robert C Rintoul, Rawya Ahmed, Brendan Dougherty, Nicholas R Carroll
Journal: Thorax (2014)

Linear endobronchial ultrasound was first described in 2003. Since then the technique has spread rapidly and has now become an established practice in many centres as the first-line mediastinal investigation for the diagnosis and staging of lung cancer. In combination with endoscopic ultrasound, the majority of the mediastinum can be assessed and this approach has been shown to have equivalent accuracy to surgical staging. This strategy is also cost-effective. New tissue processing techniques using liquid-based thin-layer cytology and cell blocks have increased diagnostic yield using immunohistochemical staining and molecular diagnostics. Several meta-analyses of case series and, more recently, randomised controlled trials have provided high-level evidence of efficacy leading to incorporation into national lung cancer staging guidelines. In addition, linear endobronchial ultrasound is increasingly used in the investigation of mediastinal lymphadenopathy for suspected sarcoidosis, tuberculosis and lymphoma. While undoubtedly endobronchial/endoscopic ultrasound has reduced the need for surgical staging in lung cancer, the latter still has an important role to play in certain scenarios. The challenge now facing clinicians is to learn to apply the appropriate test or sequence of tests in each patient while ensuring that operators are appropriately trained in order to ensure optimal outcomes.
The Treatment of Syphilis by Moist Mercurial Fumigation
Authors: J. St. S. Wilders
Journal: BMJ (1875)

were short of hands, he was occasionally accepted as a volunteer assistant at the surgical dressings.All seemed to be going on well till the seventh week from admission, when he complained of inability to put on his coat, which he ascribed to rheumatism.A day or two later, his gait was dragging,
Distribution of Obstructive Intimal Lesions and Their Cellular Phenotypes in Chronic Pulmonary Hypertension
Authors: EUNHEE S. YI, HOJOONG KIM, HYEKYUNG AHN, JENNIFER STROTHER, TIMOTHY MORRIS, ELIEZER MASLIAH, LAWRENCE A. HANSEN, KYUNGJOO PARK, PAUL J. FRIEDMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated the distribution of pulmonary arteriopathy in chronic pulmonary hypertension (PH) in a quantitative histopathologic study, using computer-assisted image analysis. We also examined the histologic manifestations and cellular phenotypes of various obstructive intimal lesions in PH with an immunohistochemical method. A total of 53 lungs removed at autopsy or explantation were obtained for the study from 51 documented cases of moderate to severe PH (15 cases of primary pulmonary hypertension [PPH], eight cases of Eisenmenger's syndrome [EISEN], 22 cases of chronic major-vessel thromboembolic disease [CTED], and three cases of PH associated with other known causes), and two unused donor lungs served as normal controls. Intimal thickening in PPH was most prominent in small pulmonary arteries and arterioles less than 200 micrometer in diameter. Plexiform lesions in PPH were associated with significantly smaller arteries than in EISEN. Arteries larger than 400 micrometer showed a significant intimal thickening only in CTED. Obstructive intimal lesions in PH comprised a morphologic spectrum with frequent intermediate forms between plexiform and thrombotic lesions. Most cells within various intimal lesions showed an immunoprofile of myofibroblasts that were positive for vimentin and alpha-smooth muscle actin, but negative for desmin and endothelial markers including Factor VIII, clonal designator (CD)31, and CD34. Endothelial markers were positive only in the single layer of cells lining slitlike lumens, when the latter were present. In conclusion, major types of PH had characteristic distribution patterns of obstructive intimal lesions, showing mainly a myofibroblastic phenotype and variable endothelial/vascular differentiation.
Neovascularisation and pain in jumper’s knee: a prospective clinical and sonographic study in elite junior volleyball players
Authors: K Gisslén, H Alfredson
Journal: British Journal of Sports Medicine (2005)

The nature of tendon neovascularisation associated with pain over time has not been studied.To prospectively study the patellar tendons in elite junior volleyball players.The patellar tendons in all students at the Swedish National Centre for high school volleyball were evaluated clinically and by ultrasonography (US) and Power Doppler (PD) sonography.Altogether 120 patellar tendons were followed for 7 months. At inclusion, jumper's knee was diagnosed clinically in 17 patellar tendons. There were structural changes on US in 14 tendons, in 13 of which PD sonography showed neovascularisation. There were 70 clinically normal tendons with normal US and PD sonography, 24 clinically normal tendons with abnormal US but normal PD sonography, and nine clinically normal tendons with abnormal US and neovascularisation on PD sonography. At 7 month follow up, jumper's knee was diagnosed clinically and by US in 19 patellar tendons, in 17 of which there was neovascularisation. Three of nine clinically normal tendons with structural changes and neovascularisation at inclusion developed jumper's knee. Two of 24 tendons clinically normal at inclusion, with abnormal US but normal PD sonography, developed jumper's knee with abnormal US and neovascularisation on PD sonography. A total of 20 clinically normal tendons with normal US and PD sonography at inclusion developed structural tendon changes and 12 of these also developed neovascularisation.The clinical diagnosis of jumper's knee is most often associated with neovascularisation in the area with structural tendon changes. The finding of neovessels might indicate a deterioration of the condition.
Reversible Insufficiency in Chronic Renal Disease
Authors: George L. Ackerman
Journal: JAMA (1966)

When renal function is decreased to approximately 30% of normal, further decreases, even though minor, produce major changes in the blood urea nitrogen level. In the presence of chronic renal disease such a change may precipitate uremia in a previously compensated patient. An important feature of the management of patients with chronic renal failure is the recognition and correction of conditions that lead to further deterioration of already compromised renal function. Sodium depletion and hypovolemia, urinary tract obstruction, systemic or renal infection, and major surgery of trauma are common causes of reversible uremia in patients with chronic renal failure. Discovery and treatment of these complications may relieve symptoms and prolong life in patients whose outlook is otherwise hopeless.
A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer
Authors: A.G. Pallis, I. Boukovinas, A. Ardavanis, I. Varthalitis, N. Malamos, V. Georgoulias, D. Mavroudis
Journal: Annals of Oncology (2011)
Altered protein expression in serum from endometrial hyperplasia and carcinoma patients
Authors: Yi-sheng Wang, Rui Cao, Hong Jin, Yi-ping Huang, Xiao-yan Zhang, Qing Cong, Yi-feng He, Cong-jian Xu
Journal: Journal of Hematology & Oncology (2011)

Abstract Background Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions. Methods In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™), and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database. Results In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein. Conclusions The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.
Malignant melanoma in the elderly.
Authors: H J Cohen, E Cox, K Manton, M Woodbury
Journal: Journal of Clinical Oncology (1987)

Advancing age is associated with poorer prognosis in malignant melanoma. We studied 3,872 cases of malignant melanoma to evaluate whether the effect of age could be analyzed relative to sex, tumor depth, primary site, and other clinical and pathologic variables. The sex distribution by age shows a slight female predominance in the early and late decades but male predominance in the middle years. The percentage of patients with metastatic disease at initial diagnosis did not vary with age, despite greater diameter and depth of lesions in the older patients. In fact, in the older age groups, initial nodal metastasis occurred slightly less frequently. Trunk primaries decreased in frequency with increasing age, while extremity lesions remained relatively constant, and face, nose, and ear lesions increased. This was in part related to the histopathologic type, as lentigo maligna lesions increased in frequency with age, superficial spreading lesions were somewhat less frequent in the older age group and nodular types were fairly constant. On the basis of both Clark's level and Breslow thickness, there was an increasing proportion of deeper penetrating lesions in the older age group. The mean diameter of these lesions on the skin surface was also greater for the older patients. This would suggest that lesions in the older individual remain confined to the local site longer, penetrate and spread, but do not necessarily metastasize more rapidly. Cox model regression analysis of survival time within stage showed that age was highly significant as a poor prognostic factor. Though the adverse relation of advancing age with survival was partially explained by predominance of other unfavorable factors, such as primary site, depth of lesion, or histologic type, age remained an independent poor prognostic factor (chi 2 = 5.3; P = .02) for death due to melanoma.
MYC Acts via the PTEN Tumor Suppressor to Elicit Autoregulation and Genome-Wide Gene Repression by Activation of the Ezh2 Methyltransferase
Authors: Mandeep Kaur, Michael D. Cole
Journal: Cancer Research (2012)

The control of normal cell growth is a balance between stimulatory and inhibitory signals. MYC is a pleiotropic transcription factor that both activates and represses a broad range of target genes and is indispensable for cell growth. Whereas much is known about gene activation by MYC, there is no established mechanism for the majority of MYC-repressed genes. We report that MYC transcriptionally activates the PTEN tumor suppressor in normal cells to inactivate the phosphoinositide 3-kinase (PI3K) pathway, thus suppressing AKT activation. Suppression of AKT enhances the activity of the EZH2 histone methyltransferase, a subunit of the epigenetic repressor Polycomb Repressive Complex 2 (PRC2), while simultaneously stabilizing the protein. MYC-mediated enhancement in EZH2 protein level and activity results in local and genome-wide elevation in the repressive H3K27me3 histone modification, leading to widespread gene repression including feedback autoregulation of the MYC gene itself. Depletion of either PTEN or EZH2 and inhibition of the PI3K/AKT pathway leads to gene derepression. Importantly, expression of a phospho-defective EZH2 mutant is sufficient to recapitulate nearly half of all MYC-mediated gene repression. We present a novel epigenetic model for MYC-mediated gene repression and propose that PTEN and MYC exist in homeostatic balance to control normal growth, which is disrupted in cancer cells.
Phase I study of apoptosis gene modulation with oblimersen within preoperative chemotherapy in patients with primary breast cancer
Authors: J. Rom, G. von Minckwitz, F. Marmé, B. Ataseven, D. Kozian, M. Sievert, B. Schlehe, F. Schuetz, A. Scharf, M. Kaufmann, C. Sohn, A. Schneeweiss
Journal: Annals of Oncology (2009)
IL-32, a novel cytokine with a possible role in disease
Authors: C A Dinarello, S-H Kim
Journal: Annals of the Rheumatic Diseases (2006)

IL-32 is the name given to the NK4 transcript first reported in IL-2 activated T lymphocytes and natural killer cells 13 years ago without known function. The novel cytokine has six isoforms. In an study to isolate a soluble form of the IL-32 receptor from human urine, IL-32α bound proteinase-3 with high affinity and was not affected by enzyme inhibition. IL-32α/IL-32γ were expressed as recombinant molecules. The cytokine exhibits properties characteristic of proinflammatory cytokines and also induces the degradation of inhibitory κB and phosphorylation of mitogen activated protein p38. Monoclonal antibodies to IL-32 identify its presence in a variety of human tissues from diseases states. Epithelial cells from healthy subjects express low levels of the cytokine, but in disease conditions such as chronic obstructive pulmonary disease, Crohn's disease and psoriasis, the expression increases markedly. IL-32 is a major transcript in gene array studies in epithelial cells stimulated with IFNγ in vitro. In rheumatoid arthritis, synovial tissues reveals increased content of IL-32, which correlates with severity of disease. A highly significant correlation has been observed between the number of synovial and macrophagic cells positive for IL-32 and the level of erythrocytes sedimentation, IL-1β, tumour necrosis factor α, and IL-18. Thus, IL-32 exhibits many properties of proinflammatory cytokines and associations with disease severity.