tbuckley/cabot-search huggingface dataset:
Prognostic Analysis for Survival in Adult Solid Organ Transplant Recipients With Post-Transplantation Lymphoproliferative Disorders
Authors: Irene M. Ghobrial, Thomas M. Habermann, Matthew J. Maurer, Susan M. Geyer, Kay M. Ristow, Timothy S. Larson, Randall C. Walker, Stephen M. Ansell, William R. Macon, Gregory G. Gores, Mark D. Stegall, Christopher G. McGregor
Journal: Journal of Clinical Oncology (2005)

The objective of this study was to determine prognostic factors for overall survival in patients with post-transplantation lymphoproliferative disorders (PTLDs).This study focused on the 107 adult solid organ transplantation patients who were diagnosed with PTLDs at Mayo Clinic (Rochester, MN) between December 1970 and May 2003.The median age at the time of diagnosis was 48 years (range, 15 to 75 years). Extranodal disease including grafted organ involvement was present in 85 patients (80%). The graft organ was involved in 30 patients (28%). At the time of these analyses, 62 patients (58%) had died. The median survival for the entire cohort was 31.5 months (95% CI, 10.7 to 72.5 months). The median follow-up of living patients was 51.8 months (range, 5.6 to 202.6 months). In univariate analyses for overall survival from the time of PTLD diagnosis, the following poor prognostic factors were identified: poor performance status with Eastern Cooperative Oncology Group levels 3 and 4 (P < .0001), grafted organ involvement (P = .0005), the presence of one or more extranodal sites (P = .005), both nodal and extranodal disease (P = .002), high International Prognostic Index (P = .006), advanced stage (P = .001), and elevated lactate dehydrogenase (P = .03). A final multivariable model for survival was constructed using three factors: poor performance status (3 to 4), monomorphic disease, and graft organ involvement.A prognostic model has been developed for PTLD patients using one center's 30 years of experience. We propose additional confirmation and validation of these prognostic factors in larger prospective studies.
The pathogenesis of coronary artery disease. A possible role for methionine metabolism.
Authors: D E Wilcken, B Wilcken
Journal: Journal of Clinical Investigation (1976)

Homocystinuria, an abnormality of methionine metabolism is associated with severe vascular disease in infancy and childhood. Homocysteine is formed during the metabolism of methionine and accumulations of this and of cysteine-homocysteine mixed disulfide in the plasma indicate a partial block in the methionine degradation pathway. Methionine metabolism was investigated in 25 patients aged under 50 with angiographically proved coronary artery disease and in 22 control patients, of whom 17 had normal coronary arteries at angiography and 5 were healthy volunteers. After an overnight fast, venous blood was drawn before and 4 h after oral L-methionine, 100 mg/kg. Plasma methionine levels at 4 h were not different in the two groups, but there were significant differences in the levels of cysteine-homocysteine mixed disulfide. This was detected in 5 of 22 in the noncoronary group and in higher concentration in 17 of 25 coronary patients (P less than 0-01). Age, weight, height, body-mass index, glucose tolerance, fasting serum urate, and triglycerides were not different, but serum cholesterol was higher in the coronary patients (P lessthan 0.01). These results suggest a reduced ability to metabolise homocysteine in some patients with premature coronary artery disease when this pathway is stressed.
Comparison of the yield of spiral enteroscopy to wireless capsule endoscopy findings: report from a single UK centre
Authors: E. A. Arthurs, P. Marden, S. Hughes
Journal: Gut (2011)

<h3>Introduction</h3> Spiral enteroscopy (SE) is used to evaluate and treat lesions affecting the small intestine. Abnormalities are often initially found using other diagnostic tools such as radiological imaging and wireless capsule endoscopy (WCE). There is little published data evaluating the findings of SE in patients with abnormalities seen at prior capsule endoscopy. The aim is to evaluate the diagnostic yield of spiral enteroscopy and compare findings in patients who had previously had wireless capsule endoscopy in a single UK centre. <h3>Methods</h3> A retrospective analysis of case notes of all patients undergoing WCE followed by SE was performed. Data regarding patient demographics, indications for WCE, WCE findings, subsequent SE findings and therapy performed was collected and analysed. <h3>Results</h3> 22 patients had capsule endoscopies followed by SE. Two patients had repeat WCE and two had SE twice. SE was performed orally on 23 occasions and once per rectum. There were 17 male and 7 female patients. Mean age was 70.6 (range 40–90). Indications for WCE were recurrent iron deficiency anaemia (11), gastrointestinal bleeding/melaena (5), occult gastrointestinal bleeding (5), anaemia and abdominal pain (2), and abdominal pain (1). Findings on WCE included angiodysplasia (9), normal examination (6), ulceration (3), small bowel diverticula (2), polyps (2), ulceration (2), findings suspicious for angiodysplasia (2), strictures (1) and nodular lymphoid hyperplasia (1). Two patients had more than one abnormality identified. The mean time from WCE to SE was 190.9 days (range 28–850). All SEs were performed under conscious sedation. The estimated depth of insertion was available for 20 patients, with a mean of 215.2 cm (range 100–300 cm) per oral, and 50 cm from the ICV per rectum. Mean time for the procedure in 20 patients was 40.5 min (range 25–65). Abnormalities were found by SE in 14 (70%) cases. Findings on WCE were reproduced at SE in 19 cases (79.2%). In three cases, SE found additional pathology not seen at WCE (two angiodysplasia, one jejunal diverticulae). In two cases SE clarified suspicious but non diagnostic abnormalities seen at WCE (angiodysplasia) and in two cases of small bowel polyps seen at WCE, SE confirmed a diagnosis of polypoid lymphangiectases. Thirteen cases (54.2%) underwent therapy in the form of APC with complete haemostasis in all. <h3>Conclusion</h3> In our experience, SE is able to locate pathology found on WCE in 79.2% of cases, but it may also find additional pathology and clarify non diagnostic findings. SE also permits therapy and complements WCE in the management of patients with suspected small bowel pathology.
US Senate committee launches investigation into drug pricing
Authors: M. McCarthy
Journal: BMJ (2015)

In response to reports that several drug companies have substantially jacked up prices by as much as 5000% after acquiring rights to older off-patent drugs, a US Senate committee has launched an investigation into pricing of prescription drugs. 

The bipartisan investigation by the Senate Special Committee on Aging will be led by Senator Claire McCaskill, a Democrat from Missouri, and Senator Susan Collins, a Maine Republican.

In a statement announcing the investigation, McCaskill said that the recent price increases seemed to have no relation to research and development costs. She said, “Some of the recent actions we’ve seen in the pharmaceutical industry—with corporate acquisitions followed by dramatic increases in the prices of pre-existing drugs—have looked like little more than price gouging.”

The investigation will look at increases in prices of recently acquired off-patent drugs; mergers and acquisitions within the …
Increased expression of lysyl oxidase in skin with scleroderma
Authors: M. CHANOKI, M. ISHII, H. KOBAYASHI, H. FUSHIDA, N. YASHIRO, T. HAMADA, A. OOSHIMA
Journal: British Journal of Dermatology (2006)

Lysyl oxidase initiates cross-linkage of collagen and elastin by catalysing the formation of a lysine-derived aldehyde. In order to study cross-linking in scleroderma, we used monoclonal antibodies to lysyl oxidase to determine the localization of this enzyme in systemic and localized scleroderma, and compared the distributions obtained with that in normal skin. Using an indirect immunofluorescent antibody method and an avidin-biotinylated enzyme complex method, 11 cases of diffuse type of systemic scleroderma and seven cases of localized scleroderma were studied. In the oedematous stage of systemic scleroderma, intracellular and extracellular lysyl oxidase were remarkably increased in the dermis, particularly in groups around blood vessels. In the sclerotic stage of systemic scleroderma, lysyl oxidase was detected intracellularly in fibroblasts and extracellularly among collagen bundles between the lower dermis and the subcutaneous fat tissue. In localized scleroderma, a marked increase in lysyl oxidase was observed in mononuclear cells and fibroblasts near blood vessels in the lower dermis and in the subcutaneous fat tissue, in addition to the extracellular deposits between collagen bundles. The increase in lysyl oxidase in localized scleroderma was much more common than in the oedematous stage of systemic scleroderma. These findings indicated that intracellular and extracellular expression of lysyl oxidase expression was greater in sclerodermatous skin than in normal skin.
Combined 18F-fluorodeoxyglucose-positron emission tomography and computed tomography as a primary screening method for detecting second primary cancers and distant metastases in patients with head and neck cancer
Authors: S.Y. Kim, J.-L. Roh, N.-K. Yeo, J.S. Kim, J.H. Lee, S.-H. Choi, S.Y. Nam
Journal: Annals of Oncology (2007)
Changes in chemical coding of myenteric neurones in ulcerative colitis
Authors: M Neunlist
Journal: Gut (2002)

Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel diseases but it is still uncertain whether neurochemical coding of myenteric neurones is altered in ulcerative colitis (UC).In this study we investigated transmitter co-localisation in myenteric neurones of normal colon and the colon of patients with UC.Choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal peptide (VIP), and substance P (SP) were detected by immunohistochemical methods in whole mounts of colonic myenteric plexus of UC patients (n=10) and controls (n=8).The proportion of ChAT positive and VIP positive neurones relative to the NSE population did not differ in inflamed (33.3% and 9.3%, respectively) and non-inflamed segments (33.6% and 9.7%) of UC colon compared with controls (35.0% and 6.9%). The proportion of SP positive neurones was significantly larger in both inflamed (15.5%) and non-inflamed (20.3%) segments than in controls (5.9%). Analysis of changes in subpopulations showed that 26.9% of neurones were only ChAT positive in controls but that the proportion was significantly smaller in inflamed (18.8%) and non-inflamed (15.8%) areas of UC. The proportions of neurones containing ChAT and SP were significantly higher in inflamed (11.8%) and non-inflamed (13.9%) areas than in controls (5.0%).Remodelling of myenteric neurones in UC involves a shift from mainly cholinergic to more SP positive innervation. This effect may constitute part of the neuronal basis for the motility disturbances observed in UC.
Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys.
Authors: M Brezis, S N Heyman, D Dinour, F H Epstein, S Rosen
Journal: Journal of Clinical Investigation (1991)

We investigated the role of the endothelial-derived relaxing factor nitric oxide (NO) in the homeostasis of O2 supply to the renal medulla, a region normally operating on the verge of hypoxia. Sensitive Clark-type O2 microelectrodes were inserted into renal cortex and medulla of anesthetized rats. The inhibitor of NO formation, L-NG-monomethylarginine (LNMMA), while increasing blood pressure and reducing renal blood flow, decreased medullary pO2 from 23 +/- 3 mmHg to 12 +/- 3 (P less than 0.001), with no change in the cortex. These responses were promptly reversed by L-arginine, which bypasses the LNMMA blockade. In isolated rat kidneys, LNMMA reduced perfusion flow without altering glomerular filtration rate, and augmented deep medullary hypoxic injury to thick ascending limbs from 68 to 90% of the tubules (P less than 0.02). These changes were prevented by L-arginine. Nitroprusside had a protective effect upon thick limb injury. Finally, in a previously reported model of radiocontrast nephropathy (1988. J. Clin. Invest. 82:401), LNMMA increased the severity of renal failure (final plasma creatinine from 2.3 +/- 2 mg% to 3.4 +/- 3, P less than 0.005) and the proportion of damaged thick limbs (from 24 +/- 6% to 53 +/- 9, P less than 0.01). Nitrovasodilatation may participate in the balance of renal medullary oxygenation and play an important role in the prevention of medullary hypoxic injury.
S6K1 Plays a Key Role in Glial Transformation
Authors: Jean L. Nakamura, Edna Garcia, Russell O. Pieper
Journal: Cancer Research (2008)

Abstract The mammalian target of rapamycin (mTOR) is a nutrient and ATP sensor suggested to play an important role in tumorigenesis, particularly in the setting of PTEN loss or activated Akt/PKB. Of mTOR's two known effectors, eIF4E has been implicated in tumorigenesis, whereas the role of S6 kinase (S6K1) in transformation is less understood. To assess the contribution of S6K1 to the transformed phenotype, we pharmacologically and genetically manipulated the mTOR-S6K pathway in glioma cells and monitored its effects on growth in soft agar, a hallmark of cellular transformation, and also assessed in vivo intracranial growth. Anchorage-independent growth by HRasV12-transformed human astrocytes as well as by U251 and U373 human glioma cells was inhibited by pharmacologic mTOR inhibition. Similarly, short hairpin RNA–mediated suppression of mTOR also reduced anchorage-independent growth of glioma cell lines. Expression of wild-type eIF4E in rapamycin-treated E6/E7/hTert/HRasV12 and U373 cells failed to rescue colony formation, although expression of wild-type S6K1 or rapamycin-resistant S6K1 in rapamycin-treated U373 and U251 provided partial rescue. Consistent with the latter observation, small interfering RNA–mediated suppression of S6K1 in HRasV12-transformed human astrocytes, U251, and U373 cells resulted in a significant loss of anchorage-independent growth. Furthermore, we found that in vivo short hairpin RNA–mediated suppression of S6K1 in HRasV12-transformed human astrocytes reduced intracranial tumor size, in association with reduced tumor levels of phosphorylated ribosomal protein S6. These findings implicate the mTOR-S6K pathway as a critical mediator of glial cell transformation. [Cancer Res 2008;68(16):6516–23]
Accuracy and precision of fourteen pulse oximeters
Authors: B Hannhart, JP Haberer, C Saunier, MC Laxenaire
Journal: European Respiratory Journal (1991)

Two sets of seven pulse oximeters (Criticare CSI-502; Nellcor-N200; Datex-Satlite; Physio-Control-Lifestat 1600; Critikon-Oxyshuttle; Ohmeda-Biox 3700; Ohmeda-Biox 3740; Radiometer-Oxi; Spectramed-Pulsat; Kontron-7840; Biochem-Ox2000; Invivo-4500; Engström-EOS; Novametrix-505) were studied in two groups of eight healthy subjects, aged 26-50 yrs. The transcutaneous oxygen saturation (SpO2) was compared with arterial oxygen saturation (SaO2) measured in simultaneously with drawn blood samples (OSM2 Radiometer) at four 20 min steady-state levels of inspired oxygen fraction (FIO2) (0.21, 0.10, 0.08 and 0.07; SaO2 99-55%) in a conditioned chamber. Both the error in accuracy (mean SpO2-SaO2 difference), and the error in precision (SD of the differences) remained less than 3% for the two highest FIO2 levels (SaO2 greater than 83%) but, during deeper hypoxia, they were increased to 8% and 5%, respectively. An instrumental systematic bias affected accuracy in particular. We concluded that a good agreement between SpO2 and SaO2, as reflected by the Bartko's intraclass coefficient, was observed in nine instruments.
Listening and talking to patients
Authors: C P Seager
Journal: BMJ (1980)

Listening and talking to patients SIR,-I was delighted to read the first of the articles (27 September, p 845) by Professor Charles Fletcher on the issue of listening and talking to patients.Medical students learn their medicine by following the example of their seniors.While every attention is paid to the acquisition of the facts about the physical condition, too often insufficient attention is paid to associated emotional problems.
The Tricyclic Antidepressants
Authors: Neal R. Cutler
Journal: JAMA (1978)

Because only 9.4% of depressions are recognized at initial evaluation by primary physicians, the diagnosis of depression is important. Forty percent of a group of mixed depressions will resolve in a month without treatment, and 70% will resolve with the use of tricyclic antidepressants. Research on plasma levels of tricyclic antidepressants suggests new clinical strategies for adjusting dosages; neurochemical studies may provide an appropriate selection process for choosing a tricyclic antidepressant. (<i>JAMA</i>240:2264-2266, 1978)
Consumer-Directed Health Care
Authors: M. Gregg Bloche
Journal: New England Journal of Medicine (2006)

For the past century, a premise of health policy has been that patients are ill equipped to judge the merits of tests, treatments, and providers. Conventional wisdom says that physicians should fill this gap by acting as patients' agents, telling them about the risks and benefits of clinical alternatives and ignoring costs when assessing these alternatives.But a diverse group of business leaders and public officials intends to overturn this wisdom and radically transform the physician's role. To motivate patients to take charge of their own care, they're aiming for a wholesale shift of medical costs to consumers. To empower . . .
Localized Pelvic Neuroblastoma: Excellent Survival and Low Morbidity With Tailored Therapy—The 10-Year Experience of the French Society of Pediatric Oncology
Authors: Marc-David Leclair, Olivier Hartmann, Yves Heloury, Laurent Fourcade, Anne Laprie, Françoise Mechinaud, Caroline Munzer, Herve Rubie
Journal: Journal of Clinical Oncology (2004)

To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB).All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery.Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% +/- 4% and 84% +/- 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively).Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease.
Cardiac peroxisome proliferator-activated receptor-α activation causes increased fatty acid oxidation, reducing efficiency and post-ischaemic functional loss
Authors: Anne D. Hafstad, Ahmed M. Khalid, Martin Hagve, Trine Lund, Terje S. Larsen, David L. Severson, Kieran Clarke, Rolf K. Berge, Ellen Aasum
Journal: Cardiovascular Research (2009)

Myocardial fatty acid (FA) oxidation is regulated acutely by the FA supply and chronically at the transcriptional level owing to FA activation of peroxisome proliferator-activated receptor-α (PPARα). However, in vivo administration of PPARα ligands has not been shown to increase cardiac FA oxidation. In this study we have examined the cardiac response to in vivo administration of tetradecylthioacetic acid (TTA, 0.5% w/w added to the diet for 8 days), a PPAR agonist with primarily PPARα activity. Despite the fact that TTA treatment decreased plasma concentrations of lipids [FA and triacylglycerols (TG)], hearts from TTA-treated mice showed increased mRNA expression of PPARα target genes. Cardiac substrate utilization, ventricular function, cardiac efficiency, and susceptibility to ischaemia-reperfusion were examined in isolated perfused hearts. In accordance with the mRNA changes, myocardial FA oxidation was increased 2.5-fold with a concomitant reduction in glucose oxidation. This increase in FA oxidation was abolished in PPARα-null mice. Thus, it appears that the metabolic effects of TTA on the heart must be owing to a direct stimulatory effect on cardiac PPARα. Hearts from TTA-treated mice also showed a marked reduction in cardiac efficiency (because of a two-fold increase in unloaded myocardial oxygen consumption) and decreased recovery of ventricular contractile function following low-flow ischaemia. This study for the first time observed that in vivo administration of a synthetic PPARα ligand elevated FA oxidation, an effect that was also associated with decreased cardiac efficiency and reduced post-ischaemic functional recovery.
No normalisation of the tendon structure and thickness after intratendinous surgery for chronic painful midportion Achilles tendinosis: Figure 1
Authors: H Alfredson, E Zeisig, M Fahlström
Journal: British Journal of Sports Medicine (2008)

To characterise Achilles tendon structure and thickness a minimum of 8 years after intratendinous surgery.Fourteen patients (16 tendons; nine men and five women, mean age 43 years, range 27-55) surgically treated (intratendinous surgery) for chronic painful midportion Achilles tendinosis, were followed with clinical examination and grey-scale ultrasonography for a minimum of 8 years (range 8-16, mean 13).All patients were satisfied with the result of surgery and were active in Achilles tendon loading activities without restrictions. In all operated tendons, structural abnormalities remained and tendons remained thicker than normal tendons.Resection of tendinosis is associated with persistent structural abnormalities and thickening of the tendon 13 years after surgery, despite successful clinical outcomes.