tbuckley/cabot-search huggingface dataset:
The Spironolactone, Amiloride, Losartan, and Thiazide (SALT) Double-Blind Crossover Trial in Patients With Low-Renin Hypertension and Elevated Aldosterone-Renin Ratio
Authors: Susan J. Hood, Kevin P. Taylor, Michael J. Ashby, Morris J. Brown
Journal: Circulation (2007)

Background— There is continuing variation in diagnosis and estimated prevalence of primary hyperaldosteronism. The higher estimates encourage search for adrenal adenomas in patients with elevated ratios of plasma aldosterone to renin. However, it is more likely that patients with normal plasma K + and aldosterone belong to the polygenic spectrum of low-renin hypertension rather than have the same monogenic syndrome as classic Conn’s. Our primary hypothesis was that in low-renin patients with normal plasma K + and aldosterone, a thiazide diuretic, bendroflumethiazide, would be as effective as spironolactone in overcoming the Na + retention and lowering blood pressure. Secondary objectives were to compare the dose response for each diuretic and to evaluate amiloride as an alternative to spironolactone. Methods and Results— Fifty-seven patients entered and 51 patients completed a placebo-controlled, double-blind, randomized crossover trial. Entry criteria included low plasma renin, normal K + , elevated aldosterone-renin ratio, and a previous systolic blood pressure response to spironolactone of ≥20 mm Hg. Two doses each of spironolactone and bendroflumethiazide were compared. The crossover also included amiloride and losartan. Outcome measures were blood pressure, plasma renin, and other biochemical markers of diuretic action. Spironolactone 100 mg and bendroflumethiazide 5 mg caused similar falls in systolic blood pressure, whereas bendroflumethiazide 2.5 mg was 5/2 mm Hg less effective in reducing blood pressure than either bendroflumethiazide 5 mg or spironolactone 50 mg ( P &lt;0.005). Amiloride 40 mg was as effective as the other diuretics. Biochemical indices of natriuresis showed bendroflumethiazide to be less effective than either spironolactone or amiloride; plasma renin rose 4-fold on spironolactone but only 2-fold on bendroflumethiazide ( P =0.003). Conclusions— In hypertensive patients with a low plasma renin but normal K + , bendroflumethiazide 5 mg was as effective as spironolactone 100 mg in lowering blood pressure, despite patients being selected for a previous large fall in blood pressure on spironolactone. Because this result differs from that expected in primary hyperaldosteronism, our finding argues against low-renin hypertension including a large, undiagnosed pool of primary hyperaldosteronism. However, spironolactone was the more effective natriuretic agent, suggesting that inappropriate aldosterone release or response may still contribute to the Na + retention of low-renin hypertension.
REDUCTION IN ESTIMATED LIFETIME CANCER INCIDENCE AND MORTALITY USING CARDIAC PROSPECTIVE ECG TRIGGERED CT COMPARED TO RETROSPECTIVE GATED CT
Authors: Kelley R.H. Branch, Adam M. Alessio, Kalpana M. Kanal, William P. Shuman, James H. Caldwell, James P. Earls
Journal: Journal of the American College of Cardiology (2010)
A Lecture on Recent Progress in the Pathology and Treatment of Cerebral Paralysis
Authors: J. Althaus
Journal: BMJ (1881)

GENTLEMIEN,-I purpose, in to-day's lecture, to lay before you the results of some recent investigations into the nature and symptoms of paralysis arising from brain-disease, and will at the same time endea- vour to point ouit how far the clearer scientific notions which we have lately gained on this subject may be rendered practically useful for prognosis and treatment.Before, however, plunging into the intricacies of pathology, I must say a few words on certain anatomical features of the motor zone of the nervous centres, which are of importance for the right comprehension of the diseases to which its several portions are subject.Our systematic handbooks of anatomy-do not as yet supply that kind of knowledge which is so much required for a due appreciation of recent medical doctrines, and which has been gained, not so much by systematic slicings of brains and cords of healthy adults, as by the infinitely finer and more instructive dissections made for us by disease, and which have thrown an entirely new light on the facts of normal anatomy.This is a kind of vivisection which cannot be
Renal transplantation in children with occult neurogenic bladders drained by intermittent self catheterisation.
Authors: O H Stanley, T L Chambers, B D Pentlow
Journal: BMJ (1983)

Children with neurogenic bladders have usually not been considered for renal transplantation because of the potential complications caused by chronic infections of the urinary tract. Two girls with occult neurogenic bladders who were practising intermittent self catheterisation were given renal transplants. Both took prophylactic antibacterial agents after transplantation, and both experienced infections at some stage, but none of these infections produced a deterioration in renal function. In one patient creatinine clearance fell and signs of obstruction appeared, but this was because the patient had been catheterising herself only two or three times a week. When she resumed catheterisation four times a day creatinine clearance rose and the urographic and renographic appearances returned to normal. These results suggest that, with adequate catheterisation and urinary chemoprophylaxis, infection is not a particular problem in children with bladder dysfunction who undergo renal transplantation.
THE ECONOMICAL USE OF SOLUTIONS OF COSTLY ALKALOIDS FOR OPHTHALMIC PURPOSES
Authors: N. B. Harman
Journal: BMJ (1916)

AUGfor a second dose of the box because of the relief afforded.A sliglht general desquamationoften follows the treatment Freedom from itching is immediate.For example, we treated one man fronm the Expeditionary For-ce who had been suffering from the disease for two months, and the next day hie told us that the luxury of a long niglht's sleep, witholut scratching, lhad been perfect bliss I In very cold weather we occasionally put a small paraffin stove in the box to warm it before putting in tlle patient. Results.WVe lhave treated over two lhundrled cases, and lhave lhad about 2 per cent.returns, and in these cases we think some article of clotlling lhad escaped disinfection and thius rein- fected the patient.The cases giving the best results were those which had not been under any otlher treatment.The great merit of the treatment is tlhat cases can be returned to their unit on the same day as received and resume duty next day.We lhave treated in one box as many as twenty
Effects of pulmonary edema on regional blood volume and red blood cell transit time. Comparison of high pressure and oleic acid-induced edema.
Authors: J Y Tsang, J S Montaner, J C Hogg
Journal: Journal of Clinical Investigation (1986)

The present study was designed to determine the effects of pulmonary vascular pressure, vascular injury, and pulmonary edema on regional blood volume (Vr) and regional red blood cell (RBC) transit time (Tr) in the lung. The experiments were carried out in 15 dogs. Six served as controls, six had oleic acid-induced pulmonary edema (OAPE), and three had high pressure pulmonary edema (HPPE). Regional blood flow (Qr) was measured with 99mTc macroaggregates, Vr with 51Cr homologous RBC, and regional transit time was calculated (Vr/Qr). The dogs were killed, and the lungs removed and sampled completely. Regional extravascular lung water (EVLW) was measured in grams per gram of dry lung and ranged from 3.7 +/- 1.1 in the control group to 6.0 +/- 1.3 in OAPE and 5.6 +/- 0.6 in HPPE. The data show that in normal lungs, increased Qr was associated with a recruitment of blood volume. In OAPE, data show that regional blood volume was decreased and that vascular injury and edema formation interfered with a further increase in Vr as Qr increased. In HPPE, Vr has already fully distended and it changed little with increased blood flow. We conclude that oleic acid-induced pulmonary injury and edema interfere with vascular recruitment and shorten regional RBC transit times. HPPE, on the other hand, is associated with normal regional RBC transit times because the vessels are fully recruited.
Liver membrane antibodies in alcoholic liver disease: 1. prevalence and immunoglobulin class.
Authors: A D Burt, R S Anthony, W S Hislop, I A Bouchier, R N MacSween
Journal: Gut (1982)

Using an indirect immunofluorescence technique liver membrane antibodies of IgG and IgA class have been demonstrated in a statistically significant proportion of sera from patients with alcoholic hepatitis and alcoholic cirrhosis. IgG and IgA class antibodies were found respectively in 23 and 25% of 48 patients with alcoholic hepatitis, in 27 and 33% of 84 with active cirrhosis, and 67 and 58% of 12 with inactive cirrhosis. These results provide evidence of a humoral immune response in alcoholic liver disease which is directed against, as yet undefined, liver-cell membrane antigens.
Impact of medical education program on COPD patients
Authors: Voicu Tudorache, Cristian Oancea, Ovidiu Fira-Mladinescu, Nicoleta Bertici, Monica Marc
Journal: European Respiratory Journal (2013)

Background/Purpose: COPD exacerbations are extremely dangerous for patients. In addition to drug therapy, medical education of patients is a key aspect in the management of this disease. In this pilot study the main outcome was the assessment of the effects of intensive medical education course on COPD-related re-hospitalizations and emergency department visits and monitoring quality of life being secondary outcomes.  Methods: 24 stage IV COPD subjects were included in this study. Patients from the intervention group (IG, 12 pts.) underwent a programme comprising two components: a comprehensive medical education programme (1h/day/5days) and specific drug therapy (according GOLD guidelines). The intervention group (IG) was compared with a control group (CG) receiving usual care (only drug therapy, 12 pts). Patients underwent Spirometry and completed Saint George Respiratory Questionnaire (SGRQ) regarding the quality of life at the time of inclusion and at periodical evaluations performed every 3 months for a year.  Results: Patients included in a medical education programme showed significant decrease of exacerbation rate compared to CG. Patients in the IG group had fewer emergency department visits within a year (12 visits) compared to the CG (19 visits). Patients in the IG had significantly better quality of life (at both 3 months and 6 months) vs. patients in CG (65.49±5.48, 69.11±4.88 vs. 76.9±5.75, 74.24±5.3).  Conclusions: This study reveals that an adequate medical education programme can decrease rates of COPD-related hospitalizations and increase quality of life.
Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD
Authors: D.E. O'Donnell, T. Flüge, F. Gerken, A. Hamilton, K. Webb, B. Aguilaniu, B. Make, H. Magnussen
Journal: European Respiratory Journal (2004)

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44±13% pred): 96 patients received 18 µg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared. On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105±40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9±0.3 Borg scale units. In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.
PKCα Activation of p120-Catenin Serine 879 Phospho-Switch Disassembles VE-Cadherin Junctions and Disrupts Vascular Integrity
Authors: Emily Vandenbroucke St Amant, Mohammad Tauseef, Stephen M. Vogel, Xiao-Pei Gao, Dolly Mehta, Yulia A. Komarova, Asrar B. Malik
Journal: Circulation Research (2012)

Rationale: Adherens junctions (AJs) are the primary intercellular junctions in microvessels responsible for endothelial barrier function. Homophilic adhesion of vascular endothelial (VE) cadherin forms AJs, which are stabilized by binding of p120-catenin (p120). p120 dissociation from VE-cadherin results in loss of VE-cadherin homotypic interaction and AJ disassembly; however, the signaling mechanisms regulating p120 dissociation from VE-cadherin are not understood. Objective: To address the mechanism of protein kinase C (PKC)-α function in increasing endothelial permeability, we determined the role of PKCα phosphorylation of p120 in mediating disruption of AJ integrity. Methods and Results: We showed that PKCα phosphorylation of p120 at serine (S)879 in response to thrombin or lipopolysaccharide challenge reduced p120 binding affinity for VE-cadherin and mediated AJ disassembly secondary to VE-cadherin internalization. In studies in mouse lung vessels, expression of the phosphodeficient S879A-p120 mutant prevented the increase in vascular permeability induced by activation of the thrombin receptor PAR-1. Conclusions: PKCα phosphorylation of p120 at S879 is a critical phospho-switch mediating disassociation of p120 from VE-cadherin that results in AJ disassembly. Therefore, blocking PKCα-mediated p120 phosphorylation represents a novel targeted anti-inflammatory strategy to prevent disruption of vascular endothelial barrier function.
Dual surface makers and HTLV-I proviral DNA in a cutaneous tumour nodule in a case of adult T cell leukaemia/lymphoma
Authors: K. MAEDA, K. YAMANA, H. TAKAHASHI, K. JIMBOW
Journal: British Journal of Dermatology (1987)

Journal Article Dual surface makers and HTLV‐I proviral DNA in a cutaneous tumour nodule in a case of adult T cell leukaemia/lymphoma Get access K. MAEDA, K. MAEDA Department of Dermatology, Sapporo Medical College, Sapporo, Japan Search for other works by this author on: Oxford Academic Google Scholar K. YAMANA, K. YAMANA Department of Dermatology, Sapporo Medical College, Sapporo, Japan Search for other works by this author on: Oxford Academic Google Scholar H. TAKAHASHI, H. TAKAHASHI Department of Dermatology, Sapporo Medical College, Sapporo, Japan Search for other works by this author on: Oxford Academic Google Scholar K. JIMBOW K. JIMBOW Department of Dermatology, Sapporo Medical College, Sapporo, Japan Kowichi Jimbow, M.D., Division of Dermatology, Faculty of Medicine 2FI.I9 WC Mackenzie Health Sciences Center, The University of Alberta, Edmonton, Canada, T6G, 2R7. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 5, 1 November 1987, Pages 561–568, https://doi.org/10.1111/j.1365-2133.1987.tb07487.x Published: 01 November 1987
Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress synovial fibroblast invasion and cartilage degradation in vivo
Authors: C Fiehn
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the effect of methotrexate (MTX) and albumin coupled with methotrexate (MTX-HSA) on cartilage invasion and induction of perichondrocytic degradation by rheumatoid arthritis synovial fibroblasts (RA SF) in vivo.Human cartilage and RA SF were co-transplanted in three groups of severe combined immunodeficient mice (SCID), which received 1 mg/kg free MTX (n = 9), 1 mg/kg MTX-HSA (n = 6), or 0.9% NaCl (n = 5), respectively, intraperitoneally twice a week. After 4 weeks' treatment, the mice were killed and the implants analysed histologically.The control group had a mean (SEM) score for cartilage invasion of RA SF of 2.0 (0.26) and for perichondrocytic cartilage degradation of 1.5 (0.34). In contrast, mice which received MTX showed a significantly reduced invasion (0.78 (0.14), p<0.01) and a reduction in perichondrocytic cartilage degradation scores (0.69 (0.2), p<0.05) in comparison with the control group. Mice treated with MTX-HSA also had significantly reduced scores for RA SF invasion into the cartilage (0.92 (0.41), p<0.05) and for cartilage degradation (0.83 (0.44), p<0.05) compared with controls. The effects of MTX and MTX-HSA were not significantly different between these two groups.Treatment with MTX or MTX-HSA significantly ameliorates cartilage destruction in the SCID mouse model for human RA.
Endothelin-A Receptor Antagonism Modifies Cardiovascular Risk Factors in CKD
Authors: Neeraj Dhaun, Vanessa Melville, Scott Blackwell, Dinesh K. Talwar, Neil R. Johnston, Jane Goddard, David J. Webb
Journal: Journal of the American Society of Nephrology (2012)

Arterial stiffness and impaired nitric oxide (NO) bioavailability contribute to the high risk for cardiovascular disease in CKD. Both asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO production, and endothelin-1 (ET-1) oppose the actions of NO, suggesting that ET-1 receptor antagonists may have a role in cardiovascular protection in CKD. We conducted a randomized, double-blind, three-way crossover study in 27 patients with proteinuric CKD to compare the effects of the ET(A) receptor antagonist sitaxentan, nifedipine, and placebo on proteinuria, BP, arterial stiffness, and various cardiovascular biomarkers. After 6 weeks of treatment, placebo and nifedipine did not affect plasma urate, ADMA, or urine ET-1/creatinine, which reflects renal ET-1 production; in contrast, sitaxentan led to statistically significant reductions in all three of these biomarkers. No treatment affected plasma ET-1. Reductions in proteinuria and BP after sitaxentan treatment was associated with increases in urine ET-1/creatinine, whereas reduction in pulse-wave velocity, a measure of arterial stiffness, was associated with a decrease in ADMA. Taken together, these data suggest that ET(A) receptor antagonism may modify risk factors for cardiovascular disease in CKD.
Tumor nekrozis faktor-alfa blockers and tuberculosis – Analysis of the 6 years
Authors: Sermin Börekçi, Berna Duman, Nejdiye Mazican, Koray Tascilar, Benan Müsellim, Gül Öngen, Vedat Hamuryudan
Journal: European Respiratory Journal (2011)

Aim:  It is a known fact that risk of tubercolosis infection is increased with tumor necrosis factor-alfa (TNF-α) blocker treatment. In this study we evaluated the last 6 years follow up data of the patients who admitted to our clinic for tuberculosis scanning before and during TNF-α blocker treatment.   Method:  Total of 2335 patients9 follow up datas were evaluated between February 2005 and February 2011.Statistical analysis were done by using SPSS 15.0 statistical program.   Results:  There were 1186 (51%) male, 1149 (49%) female of total number of 2335 patients. Mean age was 40.32±14.67 years. Patients with the diagnosis of rheumatoid arthritis 785 (33.6%), ankylosing spondylitis 912 (39.1%), psoriatic arthritis 193 (8.3%), Behcet disease 85 (3.6%), Chron disease 65 (2.8%), juvenil rheumatoid artritis 142 (6.1%). 781 (33.9%) of the subjects had smoking history of an average 15.07±13.57 pack-year. 792 (33.9%) patients treated with Etanercept, 725 (31.0%) Infliximab, 567 (24.3%) Adalimumab. 66 (2.8%) patients had treatment for tuberculosis in the past, 112 (4.8%) patients had diabetes mellitus. Acording to RAED II (The Society for Research and Education in Rheumatology) Guideline; PPD was ≥5 mm in 1340 (57%), 101 (4.3%)had radiological fibrous lesion, 12 (0.5%) had contact history with tuberculosis. 1308 (56.0%) patients were given preventive treatment with Izoniazid. In these 6 years fallow up, 4 (171/100.000) patients had tuberculosis infection; 2 were miliary tuberculosis (one of them was multidrug resistant), 1 was gastrointestinal tuberculosis and the last one was relaps patient with a history of tuberculosis.   Conclusion:  This results supported that close follow up of patients who used TNF-α blocker was so important.
Cardiac Toxicity and Efficacy of Trastuzumab Combined with Pertuzumab in Patients with Trastuzumab-Insensitive Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer
Authors: Chia C. Portera, Janice M. Walshe, Douglas R. Rosing, Neelima Denduluri, Arlene W. Berman, Ujala Vatas, Margarita Velarde, Catherine K. Chow, Seth M. Steinberg, Diana Nguyen, Sherry X. Yang, Sandra M. Swain
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy. Experimental Design: Patients with measurable HER2+ metastatic breast cancer, ≤3 trastuzumab-based regimens, and left ventricular ejection fraction (LVEF) ≥55% received 8 or 6 mg/kg trastuzumab and 840 mg pertuzumab i.v. followed by 6 mg/kg trastuzumab and 420 mg pertuzumab every 3 weeks. Cardiac evaluation and tumor response were assessed every 3 and 6 weeks, respectively. Results: Eleven patients received 64 cycles of trastuzumab plus pertuzumab. A total of 92 echocardiograms and 8 cardiac magnetic resonance imaging studies were done. With the lower limit of normal LVEF 55%, left ventricular systolic dysfunction was observed in six patients, three grade 1, two grade 2, and one grade 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The objective response rate was 18%. Two patients had partial responses, three had stable disease, and six had progressive disease. The median time to progression was 6 weeks. In baseline tumors from formalin-fixed paraffin-embedded primary and/or metastatic tumor biopsies, pHER2-Y1248 trended toward an increase in patients with partial response compared with those with stable disease/progressive disease (P = 0.095). Conclusion: Trastuzumab plus pertuzumab may have clinical benefit in selected patients who have previously been treated with trastuzumab. Cardiac toxicity, although asymptomatic in most cases, was associated with this treatment. Further evaluation of efficacy of this combination is required to define the overall risks and benefits.