tbuckley/cabot-search huggingface dataset:
Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease&lt;subtitle&gt;A Randomized Controlled Trial&lt;/subtitle&gt;
Authors: Frances M. Weaver
Journal: JAMA (2009)

Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy.Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006.Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists.The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.clinicaltrials.gov Identifier: NCT00056563.
Phase I and Pharmacokinetic Study of Sorafenib in Patients With Hepatic or Renal Dysfunction: CALGB 60301
Authors: Antonius A. Miller, Daryl J. Murry, Kouros Owzar, Donna R. Hollis, Erin B. Kennedy, Ghassan Abou-Alfa, Apurva Desai, Jimmy Hwang, Miguel A. Villalona-Calero, E. Claire Dees, Lionel D. Lewis, Marwan G. Fakih, Martin J. Edelman, Fred Millard, Richard C. Frank, Raymond J. Hohl, Mark J. Ratain
Journal: Journal of Clinical Oncology (2009)

We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction.Patients were assigned to one of nine cohorts: cohort 1, bilirubin < or = upper limit of normal (ULN) and AST < or = ULN and creatinine clearance (CC) > or = 60 mL/min; cohort 2, bilirubin more than ULN but < or = 1.5x ULN and/or AST more than ULN; cohort 3, CC between 40 and 59 mL/min; cohort 4, bilirubin more than 1.5x ULN to < or = 3x ULN (any AST); cohort 5, CC between 20 and 39 mL/min; cohort 6, bilirubin more than 3x ULN to 10x ULN (any AST); cohort 7, CC less than 20 mL/min; cohort 8, albumin less than 2.5 mg/dL (any bilirubin/AST); and cohort 9, hemodialysis. Sorafenib was administered as a 400-mg dose on day 1 for PK, and continuous daily dosing started on day 8.Of 150 registered patients, 138 patients were treated. With the exception of cohorts 6 and 7, at least 12 patients per cohort were assessable, and the dose level with prospectively defined dose-limiting toxicity in less than one third of patients by day 29 was considered tolerable. No significant associations between the sorafenib PK and cohort were found.We recommend the following empiric sorafenib starting doses by cohort: cohort 1, 400 mg twice a day; cohort 2, 400 mg twice a day; cohort 3, 400 mg twice a day; cohort 4, 200 mg twice a day; cohort 5, 200 mg twice a day; cohort 6, not even 200 mg every third day tolerable; cohort 7, not defined; cohort 8, 200 mg each day; and cohort 9, 200 mg each day.
Clinical Significance and Therapeutic Potential of the Programmed Death-1 Ligand/Programmed Death-1 Pathway in Human Pancreatic Cancer
Authors: Takeo Nomi, Masayuki Sho, Takahiro Akahori, Kaoru Hamada, Atsushi Kubo, Hiromichi Kanehiro, Shinji Nakamura, Koji Enomoto, Hideo Yagita, Miyuki Azuma, Yoshiyuki Nakajima
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The programmed death-1 ligand/programmed death-1 (PD-L/PD-1) pathway has been recently suggested to play a pivotal role in the immune evasion of tumors from host immune system. In this study, we tried to reveal the clinical importance and therapeutic potential of the PD-L/PD-1 pathway in pancreatic cancer, which is one of the most aggressive and intractable malignant tumors. Experimental Design: We used immunohistochemistry to investigate PD-L expression in 51 patients with pancreatic cancer who underwent surgery and explored the therapeutic efficacy of blocking the PD-L1/PD-1 pathway in murine pancreatic cancer in vivo. Results: PD-L1–positive patients had a significantly poorer prognosis than the PD-L1–negative patients, whereas there was no significant correlation of tumor PD-L2 expression with patient survival. PD-L1 expression was inversely correlated with tumor-infiltrating T lymphocytes, particularly CD8+ T cells. These clinical data have suggested that the PD-L1/PD-1 pathway may be a critical regulator in human pancreatic cancer. Monoclonal antibodies against PD-L1 or PD-1 induced a substantial antitumor effect on murine pancreatic cancer in vivo. PD-L1 blockade promoted CD8+ T-cell infiltration into the tumor and induced local immune activation. Furthermore, the combination of anti–PD-L1 monoclonal antibody and gemcitabine exhibited a significant synergistic effect on murine pancreatic cancer and resulted in complete response without overt toxicity. Conclusion: Our data suggest for the first time that PD-L1 status may be a new predictor of prognosis for patients with pancreatic cancer and provide the rationale for developing a novel therapy of targeting the PD-L/PD-1 pathway against this fatal disease.
Environmental nitrogen dioxide causes a pro-allergic response in the bronchial epithelium of normal subjects in vivo
Authors: G P Currie
Journal: Thorax (2003)

▴ Pathmanathan S, Krishna MT, Blomberg A, et al . Repeated daily exposure to 2 ppm nitrogen dioxide upregulates the expression of IL-5, IL-10, IL-13 and ICAM-1 in the bronchial epithelium of healthy human airways. Occup Environ Med2003;60:892–6 [OpenUrl][1][Abstract/FREE Full Text][2] High levels of nitrogen dioxide (NO2) are associated with asthma related morbidity and mortality although the precise mechanisms surrounding this remain unclear. This study evaluated the effects of in vivo NO2 exposure on expression of a … [1]: {openurl}?query=rft.jtitle%253DOccupational%2Band%2BEnvironmental%2BMedicine%26rft.stitle%253DOccup.%2BEnviron.%2BMed.%26rft.issn%253D1351-0711%26rft.aulast%253DPathmanathan%26rft.auinit1%253DS%26rft.volume%253D60%26rft.issue%253D11%26rft.spage%253D892%26rft.epage%253D896%26rft.atitle%253DRepeated%2Bdaily%2Bexposure%2Bto%2B2%2Bppm%2Bnitrogen%2Bdioxide%2Bupregulates%2Bthe%2Bexpression%2Bof%2BIL-5%252C%2BIL-10%252C%2BIL-13%252C%2Band%2BICAM-1%2Bin%2Bthe%2Bbronchial%2Bepithelium%2Bof%2Bhealthy%2Bhuman%2Bairways%26rft_id%253Dinfo%253Adoi%252F10.1136%252Foem.60.11.892%26rft_id%253Dinfo%253Apmid%252F14573722%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=oemed&resid=60/11/892&atom=%2Fthoraxjnl%2F59%2F1%2F10.atom
Lactate Dehydrogenase in Normal Mammary Glands and in 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Mammary Tumors in Sprague-Dawley Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: C Lee, L Oliver, E L Coe, R Oyasu
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Lactate Dehydrogenase in Normal Mammary Glands and in 7,12-Dimethylbenz[a]anthracene-Induced Mammary Tumors in Sprague-Dawley Rats Get access Chung Lee, Chung Lee Search for other works by this author on: Oxford Academic PubMed Google Scholar Lyda Oliver, Lyda Oliver Search for other works by this author on: Oxford Academic PubMed Google Scholar Elman L. Cae, Elman L. Cae Search for other works by this author on: Oxford Academic PubMed Google Scholar Ryoichi Oyasu Ryoichi Oyasu Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 1, January 1979, Pages 193–199, https://doi.org/10.1093/jnci/62.1.193 Published: 01 January 1979 Article history Received: 09 May 1978 Accepted: 24 July 1978 Published: 01 January 1979
A Small Tim Homohexamer in the Relict Mitochondrion of Cryptosporidium
Authors: Felicity Alcock, Chaille T. Webb, Pavel Dolezal, Victoria Hewitt, Miguel Shingu-Vasquez, Vladimir A. Likić, Ana Traven, Trevor Lithgow
Journal: Molecular Biology and Evolution (2011)

The apicomplexan parasite Cryptosporidium parvum possesses a mitosome, a relict mitochondrion with a greatly reduced metabolic capability. This mitosome houses a mitochondrial-type protein import apparatus, but elements of the protein import pathway have been reduced, and even lost, through evolution. The small Tim protein family is a case in point. The genomes of C. parvum and related species of Cryptosporidium each encode just one small Tim protein, CpTimS. This observation challenged the tenet that small Tim proteins are always found in pairs as α3β3 hexamers. We show that the atypical CpTimS exists as a relatively unstable homohexamer, shedding light both on the early evolution of the small Tim protein family and on small Tim hexamer formation in contemporary eukaryotes.
Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review
Authors: Philip E Lee, Sudeep S Gill, Morris Freedman, Susan E Bronskill, Michael P Hillmer, Paula A Rochon
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To review the role of oral atypical antipsychotic drugs in the management of the behavioural and psychological symptoms of dementia (BPSD). <b>Data sources</b> Medline, Embase, and the Cochrane Library. Reference lists were reviewed and experts were contacted to identify additional trials. <b>Study selection</b> Double blind randomised controlled trials that evaluated the four oral atypical antipsychotic therapies for BPSD. <b>Review methods</b> Two reviewers assessed trial validity independently. <b>Data extraction</b> Demographics of patients, study duration, dose of antipsychotic, primary end points, adverse events. <b>Results</b> 77 abstracts were reviewed. Five randomised trials (1570 patients) evaluating risperidone and olanzapine were identified. The quality of trials was generally good. Most participants were in an institution (&gt; 96%), elderly (weighted mean 82.3 years), and had Alzheimer9s disease (76.3%). Trials lasted 6-12 weeks. Treatment with atypical antipsychotic drugs was superior to placebo for the primary end point in three of the five trials. Two trials comparing risperidone with haloperidol did not find any differences in the primary measures of efficacy. Adverse events were common and included extrapyramidal symptoms, somnolence, and abnormal gait. <b>Conclusions</b> Although atypical antipsychotic drugs are being used with increasing frequency, few randomised trials have evaluated their use for BPSD. Limited evidence supports the perception of improved efficacy and adverse event profiles compared with typical antipsychotic drugs.
The Right Ventricle in Pulmonary Arterial Hypertension
Authors: John J. Ryan, Stephen L. Archer
Journal: Circulation Research (2014)

The right ventricle (RV) is the major determinant of functional state and prognosis in pulmonary arterial hypertension. RV hypertrophy (RVH) triggered by pressure overload is initially compensatory but often leads to RV failure. Despite similar RV afterload and mass some patients develop adaptive RVH (concentric with retained RV function), while others develop maladaptive RVH, characterized by dilatation, fibrosis, and RV failure. The differentiation of adaptive versus maladaptive RVH is imprecise, but adaptive RVH is associated with better functional capacity and survival. At the molecular level, maladaptive RVH displays greater impairment of angiogenesis, adrenergic signaling, and metabolism than adaptive RVH, and these derangements often involve the left ventricle. Clinically, maladaptive RVH is characterized by increased N-terminal pro–brain natriuretic peptide levels, troponin release, elevated catecholamine levels, RV dilatation, and late gadolinium enhancement on MRI, increased 18 fluorodeoxyglucose uptake on positron emission tomography, and QTc prolongation on the ECG. In maladaptive RVH there is reduced inotrope responsiveness because of G-protein receptor kinase–mediated downregulation, desensitization, and uncoupling of β-adrenoreceptors. RV ischemia may result from capillary rarefaction or decreased right coronary artery perfusion pressure. Maladaptive RVH shares metabolic abnormalities with cancer including aerobic glycolysis (resulting from a forkhead box protein O1–mediated transcriptional upregulation of pyruvate dehydrogenase kinase), and glutaminolysis (reflecting ischemia-induced cMyc activation). Augmentation of glucose oxidation is beneficial in experimental RVH and can be achieved by inhibition of pyruvate dehydrogenase kinase, fatty acid oxidation, or glutaminolysis. Therapeutic targets in RV failure include chamber-specific abnormalities of metabolism, angiogenesis, adrenergic signaling, and phosphodiesterase-5 expression. The ability to restore RV function in experimental models challenges the dogma that RV failure is irreversible without regression of pulmonary vascular disease.
Systemic Therapy for Metastatic Colorectal Cancer: Current Options, Current Evidence
Authors: Hanna Kelly, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2005)

Combination chemotherapy regimens including irinotecan and oxaliplatin markedly improve response rate and prolong median survival over fluorouracil with leucovorin (FU/LV), and have supplanted FU/LV as the standard systemic approach for metastatic colorectal cancer. The recent availability of five active chemotherapeutic agents has doubled the median overall survival for metastatic colorectal cancer from 10 to 20 months, and though the optimal strategy for incorporation of all drugs is still unclear, current data support the use of chemotherapy doublets in first-line rather than sequential single-agent therapy. Multidrug regimens increase both response rate and the proportion of patients able to undergo potentially curative resection. In addition, as many as 20% to 30% of patients never receive second-line chemotherapy. When used as single agents, bolus and infusional FU/LV and capecitabine are similarly effective but have differing toxicity. Chemotherapy combinations that incorporate infusion of FU are less toxic and more effective than those using bolus FU dosing. Capecitabine is under study as an alternative dosing method for use in combination regimens; however, the optimal dose has not been defined and final safety and efficacy outcomes are being addressed in ongoing phase II and III investigations. Three combinations have shown excellent first-line efficacy in phase III trials--IFL with bevacizumab, FOLFOX, and FOLFIRI--but neither of these combinations is clearly superior. Sound clinical judgment must continue to guide treatment decisions while we await data regarding the optimal combination and sequence of fluorouracil, irinotecan, oxaliplatin, bevacizumab, and cetuximab.
A Case of Appendicitis with Abscess Perforating into the Bladder: Recovery
Authors: A. P. Allan
Journal: BMJ (1900)

dix invaginated into the cmacum in such a way that only a very siall portion of its distal extremity was visible.Its wall and the wall of the cacum over a circular area arouad it were hard and indurated.The appendix except for this was apparently healthy and contained no con- cretion; it was removed and the abdomen closed.After-History.-The wound was dressed and the stitches removed on September 7th, and the boy was discharged on the 21st, having had no pain since the operation.
Modulation of QT Interval During Autonomic Nervous System Blockade in Humans
Authors: André Diedrich, Jens Jordan, John R. Shannon, David Robertson, Italo Biaggioni
Journal: Circulation (2002)

It is thought that the autonomic nervous system modulates QT interval, but traditional autonomic blockade combining propranolol and atropine has produced conflicting results. We used the alternative approach of interrupting neurotransmission at the level of autonomic ganglia to determine its effect on the QT interval.We infused trimethaphan at increasing doses (0.5 to 10 mg/min IV) while monitoring heart rate, heart rate variability spectra, QT interval, and blood pressure in 10 normal volunteers, 9 patients with multiple system atrophy (MSA), and 8 patients with pure autonomic failure (PAF). The QT interval was corrected for heart rate using Bazett's formula (QTc). Patients with PAF had very low heart rate variability and a prolonged QTc at baseline (465+/-8 ms) compared with patients with MSA (448+/-6 ms) and normal subjects (432+/-6 ms). In normal subjects, trimethaphan dose-dependently prolonged QTc (to 469+/-7 ms), decreased RR interval (995+/-45 to 670+/-35 ms), and abolished heart rate variability. In MSA patients, trimethaphan also prolonged QTc (to 463+/-7 ms) and reduced heart rate variability but did not significantly change RR interval (from 813+/-38 to 801+/-39).Autonomic blockade prolongs QT interval in normal subjects to a similar duration as in PAF patients. Furthermore, blocking residual autonomic tone in PAF patients is associated with a further increase in QT interval length. Patients with MSA have greater residual sympathetic tone and greater prolongation of the QT interval during ganglionic blockade than PAF patients.
EFFECT OF ENZYME INHIBITORS AND ACTIVATORS ON THE MULTIPLICATION OF TYPHUS RICKETTSIAE
Authors: Donald Greiff, Henry Pinkerton
Journal: The Journal of Experimental Medicine (1948)

A technique is described for measuring the oxygen uptake of embryonate eggs. Statistical analysis has shown that the method is reliable and accurate. Determinations were made on groups of 15 to 20 eggs, in order to average out individual biological variations. Reduction of the CO(2) tension and relative humidity to approximately zero previous to analysis has been found to be desirable. The oxygen consumption of normal and typhus-infected eggs, untreated and treated with agents previously found to inhibit or enhance rickettsial growth has been studied. Rickettsial infection caused a slight but significant increase in the rate of oxygen consumption on the 4th day after inoculation, followed by a rapid drop in the rate as the infection developed. The evidence suggests that low concentrations of rickettsial toxins may stimulate respiration, while higher concentrations depress respiration and lead eventually to embryonic death. PABA, which is rickettsiostatic, markedly increased the oxygen uptake of normal eggs, the effect appearing 4 days after injection and lasting for about 4 days. Thereafter, the rate fell below that of the untreated eggs. In typhus-infected eggs, PABA had similar effects, but the oxygen consumption reached much higher levels. A possible explanation of this fact is suggested. MABA and OABA, which are not rickettsiostatic, did not increase oxygen uptake; in fact they depressed cellular respiration moderately, OABA being more active in this way than MABA. These two compounds may compete with PABA for a position in some respiratory enzyme system. Potassium cyanide, which enhances rickettsial growth, caused, in concentrations not lethal to the embryos, a moderate drop in the oxygen consumption of normal eggs, the effect starting almost immediately after injection and lasting usually for 9 days. In infected eggs, its effect was more striking. It is probable that rickettsial toxins and KCN act synergistically to depress cellular respiration. When PABA and KCN were injected simultaneously, the stimulating effect of PABA on respiration predominated. The resulting level of oxygen consumption, though lower than that resulting from PABA alone, was still high enough to inhibit rickettsial growth. As far as our results go, they support the hypothesis that, within certain limits, rickettsial growth is inversely proportional to the respiratory rate of the host cells, regardless of the factors which determine that rate. It is not yet clear that PABA owes its rickettsiostatic action to its ability to increase cellular respiration, but this assumption seems reasonable as a working hypothesis. The respiratory mechanism in which PABA participates is not as yet known. Although PABA forms part of the folic acid molecule, folic acid itself, in concentrations corresponding to effective doses of PABA, did not increase cellular respiration or show rickettsiostatic action.
Randomized Trial of a Color-Coded Slide Rule in Children With Diabetes
Authors: Ineke de Kruijff, H. Maarten Reeser, Wilma Oostdijk, Wilhelmina H. Stokvis-Brantsma, Anton J.M. de Craen, Arda Derksen-Lubsen
Journal: Diabetes Care (2005)

Self-management is important, but difficult, in children with diabetes. A color-coded slide rule containing a color scheme representing a treatment algorithm might help diabetic children with self-management (1). Moving the slide rule to the right moment of the day reveals a color that corresponds to the glucose value. The slide rule will describe the correct action to be undertaken. These actions include taking extra insulin but can also include consuming more carbohydrates, as well as ketone monitoring, blood glucose checking, or consulting a diabetes expert. The amount of insulin …
Frostbite at the gym: a case report of an ice pack burn.
Authors: G O'Toole, S Rayatt
Journal: British Journal of Sports Medicine (1999)

The case is reported of a 59 year old woman who suffered a 1% total body surface area superficial partial thickness burn to her calf following the application of an ice pack. The cause, resulting injury, and subsequent management are discussed. It is possible that such injuries are common, but no similar reports were found in a literature search. Awareness of the risk of this type of injury is important for all those entrusted with advising patients on the treatment of minor soft tissue injuries.
Adjuvant Radiotherapy Versus Wait-and-See After Radical Prostatectomy: 10-year Follow-up of the ARO 96–02/AUO AP 09/95 Trial
Authors: Thomas Wiegel, Detlef Bartkowiak, Dirk Bottke, Claudia Bronner, Ursula Steiner, Alessandra Siegmann, Reinhard Golz, Stephan Störkel, Normann Willich, Axel Semjonow, Michael Stöckle, Christian Rübe, Udo Rebmann, Tilman Kälble, Horst Jürgen Feldmann, Manfred Wirth, Rainer Hofmann, Rita Engenhart-Cabillic, Axel Hinke, Wolfgang Hinkelbein, Kurt Miller
Journal: European Urology (2014)