tbuckley/cabot-search huggingface dataset:
Pathogenesis of acute renal failure following temporary renal ischemia in the rat.
Authors: W J Arendshorst, W F Finn, C W Gottschalk
Journal: Circulation Research (1975)

In this study, we characterized the sequence of several intrarenal events and evaluated their relative importance in the pathogenesis of unilateral oliguric acute renal failure induced experimentally in rats by complete occlusion of a renal artery for 1 hour. Kidneys were studied prior to occlusion and 1-3 hours and 22-26 hours after release of the temporary occlusion. Renal blood flow measured by an electromagnetic flow transducer was reduced to 40-50% of control during both postocclusion periods. Flow of tubular fluid was markedly reduced, and the damaged kidneys were oliguric. Proximal and distal convolutions were filled with fluid and dilated 1-3 hours after occlusion; their pressures were greatly heterogeneous and were elevated, on the average, to 31 and 16 mm Hg, respectively. Glomerular capillary pressure at this time was normal or slightly increased. Histological sections showed extensive tubular obstruction. We conclude that initially the oliguria is primarily due to intraluminal obstruction in the absence of predominant increases in preglomerular vascular resistance. Observations at 22-26 hours after occlusion indicated acute tubular necrosis. Moreover, the combined involvement of preglomerular vasoconstriction, presisting tubular obstruction, and passive backflow of tubular fluid appeared to be important in the maintenance of the oliguria. Glomerular capillary, proximal intratubular, and peritubular capillary hydrostatic pressures were reduced below control values. After acute volume expansion, the reduced pressures and renal blood flow were reversed, yet the experimental kidneys remained oliguric. Thus, it is clear that tubular obstruction is a significant factor responsible for both the genesis and the maintenance of oliguria in this experimental model of ischemia-induced acute renal failure.
Neutrons Show Promise in Treating Some Sarcomas, Adenocarcinomas, Locally Advanced Prostate Cancers; Research Continues
Authors: Timothy F. Kirn
Journal: JAMA (1987)

IN A 1969 address to the American Society of Therapeutic Radiologists, Mary Catterall, MD, a British radiologist, predicted that ultimately all radiotherapists would be using neutrons to treat some patients. But since that early enthusiasm, there has been a steady "decrescendo" of interest, to quote one radiologist. Decrescendo is not disappointment, however, say neutron researchers. Rather, while it appears that neutron treatments are not a better form of radiotherapy overall, they may have specific applications. Recent results indicate that neutron radiotherapy is an effective treatment for bone and soft tissue sarcomas, for adenocarcinomas— in particular, salivary gland tumors— and for locally advanced prostate cancers. Robert Stone, MD, is believed to be the first physician to attempt treating patients with neutrons—in 1939 at the E. O. Lawrence Cyclotron in Berkeley, Calif, barely seven years after the British physicist Sir John Chadwick first identified the particle. But Stone's results were poor, his
Clinical trial opportunities in hemostasis and thrombosis: NHBLI State‐of‐the‐science symposium
Authors: Douglas B. Cines, Morris A. Blajchman, Katherine A. High, James B. Bussel
Journal: American Journal of Hematology (2011)

Clinical trials in hemostasis and thrombosis (HT) are needed to guide medical practice and future research. Providing public support for trials that could have the greatest impact on clinical care has been a major challenge. The National Heart, Lung and Blood Institute (NHLBI) convened a State-of-the-Science meeting in Bethesda on September 14th and 15th, 2009 to identify Phase II and III clinical trials in HT that could have critical impact on healthcare. An oversight committee composed of representatives of the NHLBI and three experienced extramural investigators chose chairs of subcommittees representing six broad areas of investigation in adult and pediatric HT. Chairs were charged with identifying important, feasible proposals. Nineteen trial concepts were presented at this public meeting, followed by open commentary from members of an independent external panel chosen to evaluate the trials and from symposium participants from the wider scientific community. Descriptions of two important clinical trial concepts from each of the six subcommittees are provided in the Supporting Information. Phase II-III clinical trials that could have high impact include studies for treatment of venous thromboembolism (TE) in children and in adults, the potential utility of statins in prophylaxis of TE, prophylaxis of adults with severe hemophilia, management of heparin-induced thrombocytopenia (HIT) and of primary immune thrombocytopenia (ITP). The external panel also provided recommendations concerning infrastructure and approach that could improve the conduct of studies including: development of core organizations with expertise in design of clinical trials, biostatistics, and contract development; funding based on output and milestones; and enhanced investment in coordinating centers.
Peterborough hospital has tissue bank on not for profit basis
Authors: C. Womack, N. Gray
Journal: BMJ (2000)

EDITOR—Josefson writes that academic hospitals in the United States are to ask patients for the right to sell their tissue.1 This comes soon after publication in the United Kingdom of a review of the issues related to setting up a human research tissue bank in the NHS (based on our experience in Peterborough)2 and new guidance on patient confidentiality by the General Medical Council.3

Originally established in 1996, our tissue bank has …
AUTORADIOGRAPHIC STUDIES OF HAIR GROAWTH IN VARIOUS DERMATOSES: INVESTIGATION OF A POSSIBLE CIRCADIAN RHYTHM IN HUMAN HAIR GROWTH
Authors: STANLEY COMAISH
Journal: British Journal of Dermatology (1969)

SUMMARY. Autoradiographic methods have been used in a study of human hair growth. Observations on patients with psoriasis and eczema have shown no difference in hair growth rate in the lesions and unaffected skin, nor between the latter and hair growth in normal controls. Mean growth during the day was greater than at night, but the difference was not statistically significant.
Anti-leukemia activity of PVP-coated silver nanoparticles via generation of reactive oxygen species and release of silver ions
Authors: Dawei Guo, Lingying Zhu, Zhihai Huang, Haixia Zhou, Yue Ge, Wenjuan Ma, Jie Wu, Xiuyan Zhang, Xuefeng Zhou, Yu Zhang, Yun Zhao, Ning Gu
Journal: Biomaterials (2013)
The Cure of Writer's Cramp
Authors: A. de Watteville
Journal: BMJ (1885)

TH3,$$g, MA,WY,N4 'M edly onsumed 4.n, ,te tissues.; .but the bloo4 -i.a. tissgtl was itself u,dergoing ¢age at all pare qf its 6o0ArWq.Oxygenjiut,,ve con- suiped, and, carbpoqic acid, produced .nt e tlungs, as welt as -ia the liver or skin.Urine in the csPillaries of te-kidney was ;not the urine of bladder,; the saliv,$ of the acini was npt the saliva of the duct; and,the bile of the gall-bladder was not the bile of the hepatic capillary ducts.Chemistry alone could teach the accurate constitu- tion of tissues, and to that science we must look for pn,ogress.Dr. CHARLES said, in reference to Dr. McVail's remaiks, that he was afraid the 1efilod of estimating the gases in liqitls pursued at present was of too complicated a nature to be niadp -se of in clinica,l investigations.As to the statement that the results of the analyses of the gases of secretions were not reliable, owing to decomposition occurmng in the secretions after death, he held that this ojection would not apply to his experiments, as they had all been made on bile flowing directly from the liver.Indeed, results of this kind were, in his opinion, as trustworthy as those derived from an inVestigation of the gases of the blood.
Left Ventricular Subendocardial Ischemia in Severe Valvar and Supravalvar Aortic Stenosis
Authors: WILLIAM R. VINCENT, GERALD D. BUCKBERG, JULIEN I. E. HOFFMAN
Journal: Circulation (1974)

Severe valvar aortic stenosis (VAS) and supravalvar aortic stenosis (SVAS) each may cause left ventricular (LV) subendocardial ischemia and infarction, even with patent coronary arteries. LV ischemia in VAS has been related to reduced coronary perfusion relative to raised metabolic requirements, whereas this mechanism of ischemia has not been widely accepted in SVAS because coronary perfusion pressure is higher than normal. LV subendocardial coronary blood flow (CBF) occurs predominantly in diastole and a diastolic pressure-time index (DPTI) was used to estimate it. LV oxygen requirements were estimated from the systolic pressure-time index (SPTI). The ratio DPTI:SPTI (supply:demand) was evaluated as an estimate of the adequacy of subendocardial flow. SVAS was produced acutely in nine dogs and phasic left CBF and distribution of CBF to the LV myocardium were measured. Although mean CBF always rose with aortic constriction, flow in diastole fell from a control of 80% to 34% ( P &lt; 0.001) and LV myocardial flow distribution became inhomogeneous with the proportion of flow to subendocardial muscle decreasing 63% ( P &lt; 0.001). Departure from the normal homogeneous flow distribution to the LV was predictable from the ratio DPTI:SPTI; values below 0.7 were always associated with relative subendocardial underperfusion. DPTI:SPTI ratios in two patients, one with severe VAS (0.25) and one with SVAS (0.39) were well below values obtained in 18 control patients (1.03 ± 0.23), and were similar to the ratios in dogs with SVAS (0.27 ± 0.08). Both patients had ECG changes suggesting LV ischemia. The mechanism of subendocardial ischemia is thought to be the same in both types of stenosis and its presence is predictable from pressure measurements available at cardiac catheterization.
USE AND COMPARATIVE EFFECTIVENESS OF CARDIAC RESYNCHRONIZATION THERAPY AMONG PATIENTS WITH HEART FAILURE AND ATRIAL FIBRILLATION: DATA FROM THE NCDR® REGISTRY
Authors: Prateeti Khazanie, Melissa Greiner, Sana Al-Khatib, Jonathan Piccini, Mintu Turakhia, Paul Varosy, Frederick Masoudi, Lesley Curtis, Adrian Hernandez
Journal: Journal of the American College of Cardiology (2014)
THU0393 Estimated Glomerular Filtration Rate is Associated with Bone Fragility in the Elderly
Authors: M. J. Gonçalves, A. Rodrigues, J. Caetano-Lopes, A. Lopes, B. Vidal, E. Raquel, M. Sarmento, H. Canhão, J. E. Fonseca, F. Vaz, J. Monteiro
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoporosis is frequently associated with renal disease, namely the bone metabolism disturbances caused by chronic kidney disease (CKD). Both diseases are highly prevalent in the elderly. The increased risk of fragility fractures is well demonstrated in patients with end-stage renal disease (ESRD). There is recent evidence that bone pathological changes start early in the course of CKD, but still little is known about bone disease in patients with mild/moderate renal impairment. <h3>Objectives</h3> Our aim is to evaluate whether chronic renal disease, in stages before ESRD, is associated with bone fragility. Bone fragility was assessed considering history of fragility fracture events, 10 year risk for major osteoporotic fractures and hip fractures (FRAX), biochemical bone turnover markers (P1NP and CTX) and mechanical testing to determine bone stiffness. <h3>Methods</h3> We studied patients admitted for hip replacement surgery. They were asked for clinical data and blood samples. Blood biomechanical studies were performed and a bone cylinder was drilled from their femoral epiphyses. Glomerular filtration rate (GFR) was estimated using Cockcroft-Gault formula; we excluded patients with obvious limitations to the application of the formula. We also excluded from the analysis patients with terminal renal impairment, with eGFR≤15ml/minute or history of renal replacement therapy. Patients with admission diagnosis of aseptic femoral head necrosis we're also excluded. <h3>Results</h3> We included 111 patients. Mean age 74.31±10.03, 70% of subjects were female, 98% Caucasian. Fragility fracture and the score FRAX had an inverted relation with eGFR (p=0.023, and for both risks p=&lt;0.0001). The biomarker CTX also showed an inverted relation with eGFR (p= 0.003). P1NP (p=0.056) and bone stiffness (coefficient 2.42, p=0.073) showed a trend for association with eGFR. All analysis were adjusted for age and gender. <h3>Conclusions</h3> Renal impairment in early stages, measured by eGFR, was associated with increased bone fragility assessed by fracture events, FRAX and bone turnover and biomechanics biomarkers, after adjustment to age and sex. Improving the understanding of bone metabolism disturbances in earlier stages of chronic renal disease might prevent the development of clinical bone disease in these patients. <h3>References</h3> Rodrigues AM, Low osteocalcin/collagen type I bone gene expression ratio is associated with hip fragility fractures. Bone. 2012 Dec;51(6):981-9. doi: 10.1016/j.bone.2012.08.129. Epub 2012 Sep 5. Iwasaki Y et al. Changes in chemical composition of cortical bone associated with bone fragility in rat model with chronickidney disease. Bone. 2011 Jun 1;48(6):1260-7. doi: 10.1016/j.bone.2011.03.672. Epub 2011 Mar 21. <h3>Disclosure of Interest</h3> None Declared
Urinary transforming growth factor ?1 levels in hepatitis C virus-related chronic liver disease: Correlation between high levels and severity of disease
Authors: J Tsai, J Jeng, L Chuang, W Chang
Journal: Hepatology (1997)

To assess the clinical relevance of transforming growth factor β 1 (TGF-β 1 ) in chronic liver disease, urinary TGF-β 1 and circulating aminoterminal propeptides of type III procollagen (PIIINP) levels were determined by radioimmunoassay in 100 cirrhotic patients, 44 patients with chronic hepatitis, and 50 healthy controls. TGF-β 1 and PIIINP levels in cirrhotic patients were higher than those in patients with chronic hepatitis (each P &lt; .0001) or healthy controls (each P &lt; .0001), respectively. There was a correlation between TGF-β 1 and PIIINP levels in patients (r = .858, P &lt; .0001). The higher the urinary TGF-β 1 level, the worse the severity of chronic liver disease ( P &lt; .001). TGF-β 1 levels in cirrhotic patients with antibodies to hepatitis C virus (anti-HCV) were higher than in those without ( P &lt;.0001). Compared with cirrhotic patients with hepatitis B surface antigen (HBsAg) alone, those with HBsAg and anti-HCV had higher TGF- β 1 levels ( P &lt; .001), a higher frequency of raised TGF-β 1 ( P &lt; .005), and a higher frequency of patients with Child-Pugh C ( P &lt; .005). Multivariate analysis indicated that the TGF-β 1 level was significantly correlated with the presence of cirrhosis. In conclusion, urinary TGF-β 1 levels may be used as a marker for hepatic fibrogenesis. Higher urinary TGF-β 1 levels correlate with more severe liver disease.
Six Kosovar doctors face charges of illegal organ trafficking
Authors: P. Lewis
Journal: BMJ (2010)

Six doctors denied running an illegal organ transplant clinic in Kosovo this week, in a case that has been linked to an international network of organised criminals.

Details of the allegations against doctors involved in the Medicus clinic, in a suburb north of the capital Pristina, emerged at a confirmation hearing in the city’s district court.

EU prosecutor Jonathan Ratel told the judge that Russians, Moldovans, Kazakhs, and Turks were lured into the capital “with the false promise of payments” for their kidneys after meeting brokers in Turkey.

After blood tests that matched them with suitable recipients, between 20 and 30 “donors” are said then to have been given plane tickets to Pristina airport between 1 January and 4 November 2008.

They were taken to the clinic, just a few kilometres from the airport, where their kidneys …
THE IMPACT OF IMPROVEMENT OF MITRAL REGURGITATION ON LONG TERM CLINICAL OUTCOMES IN PATIENTS UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY.
Authors: Kenji Ando, Satoshi Shizuta, Takeshi Arita, Riki Fujii, Kouichi Inoue, Takeshi Kimura, Takaaki Isshiki, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2010)
CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis
Authors: Geraldine Nouailles, Anca Dorhoi, Markus Koch, Jens Zerrahn, January Weiner, Kellen C. Faé, Frida Arrey, Stefanie Kuhlmann, Silke Bandermann, Delia Loewe, Hans-Joachim Mollenkopf, Alexis Vogelzang, Catherine Meyer-Schwesinger, Hans-Willi Mittrücker, Gayle McEwen, Stefan H.E. Kaufmann
Journal: Journal of Clinical Investigation (2014)

Successful host defense against numerous pulmonary infections depends on bacterial clearance by polymorphonuclear leukocytes (PMNs); however, excessive PMN accumulation can result in life-threatening lung injury. Local expression of CXC chemokines is critical for PMN recruitment. The impact of chemokine-dependent PMN recruitment during pulmonary Mycobacterium tuberculosis infection is not fully understood. Here, we analyzed expression of genes encoding CXC chemokines in M. tuberculosis–infected murine lung tissue and found that M. tuberculosis infection promotes upregulation of Cxcr2 and its ligand Cxcl5. To determine the contribution of CXCL5 in pulmonary PMN recruitment, we generated Cxcl5–/– mice and analyzed their immune response against M. tuberculosis. Both Cxcr2–/– mice and Cxcl5–/– mice, which are deficient for only one of numerous CXCR2 ligands, exhibited enhanced survival compared with that of WT mice following high-dose M. tuberculosis infection. The resistance of Cxcl5–/– mice to M. tuberculosis infection was not due to heightened M. tuberculosis clearance but was the result of impaired PMN recruitment, which reduced pulmonary inflammation. Lung epithelial cells were the main source of CXCL5 upon M. tuberculosis infection, and secretion of CXCL5 was reduced by blocking TLR2 signaling. Together, our data indicate that TLR2-induced epithelial-derived CXCL5 is critical for PMN-driven destructive inflammation in pulmonary tuberculosis.
In vitro exposure to hydroxyurea reduces sickle red blood cell deformability
Authors: Zhi Huang, Joseph G. Louderback, S. Bruce King, Samir K. Ballas, Daniel B. Kim‐Shapiro
Journal: American Journal of Hematology (2001)

Abstract Hydroxyurea is a drug that is used to treat some patients with sickle cell disease. We have measured the deformability of sickle erythrocytes incubated in hydroxyurea in vitro and found that hydroxyurea acts to decrease the deformability of these cells. The deformability of normal erythrocytes was not significantly affected by hydroxyurea except at very high concentrations. Hydroxyurea also did not consistently reduce the deformability of sickle erythrocyte ghosts. We propose that the decreased deformability, observed in vitro, is due to the formation of methemoglobin and other oxidative processes resulting from the reaction of hydroxyurea and oxyhemoglobin. Although the reaction with normal hemoglobin is similar to that of sickle hemoglobin, the sickle erythrocytes are affected more. We propose that the sickle erythrocyte membrane is more susceptible to the reaction products of the reaction of hemoglobin and hydroxyurea. An earlier report has shown that hydroxyurea increases the deformability of erythrocytes in patients on hydroxyurea. Taken together, these data suggest that the improved rheological properties of sickle erythrocytes in vivo are due to the elevated numbers of F cells [cells with fetal hemoglobin]. The presence of the nitrosyl hemoglobin or methemoglobin from the reaction with hydroxyurea may also benefit patients in vivo by reducing sickling. Am. J. Hematol. 67:151–156, 2001. © 2001 Wiley‐Liss, Inc.
A new model of murine in situ stenting: great things come in small packages
Authors: S. J. George
Journal: Cardiovascular Research (2009)

Drug-eluting stent (DES) therapy has represented a very significant milestone in the evolution of percutaneous coronary intervention (PCI) therapy. DES reduces the need of repeat intervention in the order of 35–70% compare with bare metal stents.1 However, there is still a need for research aimed at reducing restenosis since the need for re-intervention is not eliminated and certain anatomic and clinical scenarios, such as patients with diabetes mellitus, restenotic lesions after DES, bypass graft disease, and bifurcations, continue to be problematic for PCI therapy.2,3 To further reduce in-stent restenosis rates, research into improving stent and polymer design by testing and modifying drugs from various classes is necessary. To do this a relatively easy and cheap animal model is required.

Animal models of diseases and related therapies serve two main purposes: first to increase the understanding of pathobiology and secondly to evaluate new therapies down to the histopathological level. Animal models have significantly advanced our understanding of the mechanisms of restenosis and have thereby improved the therapeutic options. For many years, the porcine model of stenting4,5 has been accepted as the most appropriate model, and more than 100 manuscripts assessing the anti-restenotic value of various agents in this model have been published. It … 

*Corresponding author. Tel: +44 117 342 3154, Fax: +44 117 342 3581, Email: s.j.george{at}bris.ac.uk
Treating acute ischaemic stroke
Authors: P. M W Bath
Journal: BMJ (1995)

Still no effective drug treatment available

Now that drug treatment for acute myocardial infarction has been largely sorted out, the world of vascular medicine has moved on to acute stroke. Given that stroke is the third commonest cause of death in the West and the most important cause of adult disability,1 it is surprising that no treatment exists that has been conclusively shown to reduce the risk of death or disability. Despite a massive worldwide effort to rectify this, early results are disappointing.

In the West most (85%) strokes result from cerebral infarction after arterial occlusion. Ischaemia induces activation of the glutamate-calcium cascade and cytodestructive enzymes, the release of free radicals, and ultimately cell death.2 Surrounding the core of dead neural tissue lies a penumbra of neurones that may survive or die, which has become the focus of pharmacological activity.

The main classes of agents include thrombolytics (to accelerate reperfusion), anticoagulants and antithrombotics (to prevent further occlusion), vasodilators (to increase cerebral blood flow), antileucocytic drugs (to prevent inflammation), glutamate antagonists, calcium antagonists, and free radical scavengers. Anticoagulants, antithrombotics, and antileucocytic drugs may also reduce the early risk of deep vein thrombosis and pulmonary embolism, which are important complications of stroke.

Two sets of events have occurred recently that considerably advance our knowledge …
UN millennium health goals will not be achieved, report warns
Authors: Paul Ress
Journal: BMJ (2005)

The health objectives of the United Nations' millennium development goals will not be achieved by 2015 unless investments in national health systems are “dramatically increased” and many more doctors, nurses, midwives, and other health professionals are made available. That is the warning from the World Health Organization in its latest report evaluating progress towards the goals.

The 82 page report says that unless these goals are met “large numbers of people will continue to die of mostly preventable diseases.”

It says that among the “annual avoidable deaths in developing countries will be those of 10.6 million …