tbuckley/cabot-search huggingface dataset:
Invincible arrogance--and patients suffer
Authors: E Poole
Journal: BMJ (1981)

sprinters lack stamina, but I imagine that no one would question their cardiopulmonary fitness-while in training.I am also worried by the modified physical fitness index, as this fails to take account of the resting pulse rate.Surely a formula based on percentage increase over resting rate at two, five, and 10 minutes would seem more reasonable, since the normal resting pulse rate can vary from the 40s to the 90s at least-or does a naturally slow pulse rate confer a fitness advantage ?Interestingly, Lieutenant-ColonelPearn referred to Zatopek's fitness index of 172; he was a distance runner with a resting pulse rate of about 40 per minute.But I wonder how Zatopek would have fared on the squash court, where explosive bursts of energy are required, or in gymnastics, in which a completely different sort of fitness and body control is demanded, or in the swimming pool.He certainly would have been
OBSERVATIONS ON THE METABOLIC EFFECTS OF THE CARBONIC ANHYDRASE INHIBITOR DIAMOX®: MODE AND RATE OF RECOVERY FROM THE DRUG'S ACTION
Authors: T. Hanley, M. M. Platts
Journal: Journal of Clinical Investigation (1956)

Ingestion of certain unsubstituted sulphonamides causes an increased excretion of sodium, potassium, and bicarbonate ions. The effects are probably due to reduction of the quantity of hydrogen ions available for secretion by the renal tubules, with consequent impairment of the Na+- H+ exchange postulated by Pitts and Alexander as being responsible for the tubular reabsorption of bicarbonate ( 1 ).
Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity
Authors: Richard J. Bende, Wilhelmina M. Aarts, Robert G. Riedl, Daphne de Jong, Steven T. Pals, Carel J.M. van Noesel
Journal: The Journal of Experimental Medicine (2005)

We analyzed the structure of antigen receptors of a comprehensive panel of mature B non-Hodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)VH-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and myelomas expressed a CDR3 repertoire comparable to that of normal B cells. Mantle cell lymphomas and B cell chronic lymphocytic leukemias (B-CLLs) expressed clearly restricted albeit different CDR3 repertoires. Lymphomas of mucosa-associated lymphoid tissues (MALTs) were unique as 8 out of 45 (18%) of gastric- and 13 out of 32 (41%) of salivary gland-MALT lymphomas expressed B cell antigen receptors with strong CDR3 homology to rheumatoid factors (RFs). Of note, the RF-CDR3 homology without exception included N-region–encoded residues in the hypermutated IgVH genes, indicating that they were stringently selected for reactivity with auto-IgG. By in vitro binding studies with 10 MALT lymphoma–derived antibodies, we showed that seven of these cases, of which four with RF-CDR3 homology, indeed possessed strong RF reactivity. Of one MALT lymphoma, functional proof for selection of subclones with high RF affinity was obtained. Interestingly, RF-CDR3 homology and t(11;18) appeared to be mutually exclusive features and RF-CDR3 homology was not encountered in any of the 19 pulmonary MALT lymphomas studied.
Ionizing Radiation-Induced Adenovirus Infection Is Mediated by Dynamin 2
Authors: Jun Qian, Jiong Yang, Aleksandar F. Dragovic, Eyad Abu-Isa, Theodore S. Lawrence, Ming Zhang
Journal: Cancer Research (2005)

Abstract Specific viral targeting into intrahepatic tumors remains critical for adenovirus gene therapy in liver cancer. We previously showed that ionizing radiation increases adenovirus uptake and transgene expression in cells and colon cancer xenografts. Here, we tested whether radiation induces viral uptake through virus-cell membrane interaction. We found that radiation (8 Gy) induced adenoviral gene transfer in rat hepatocytes (WB) and human colon carcinoma cells (LoVo). This induction (24.4- and 6.5-fold, respectively) and viral uptake were significantly diminished by preincubation with antibody for Dynamin 2 but not for Coxsackie adenovirus receptor or for integrin αv. Radiation-induced Dynamin 2 expression was detected by immunohistochemical staining and by increased mRNA levels for Dynamin 2 in WB (1.5-fold) and LoVo (2.2-fold) cells. Specific small interference RNA (siRNA) transfection significantly inhibited Dynamin 2 expression in various tumor cell lines (LoVo, D54, and MCF-7) and abolished the radiation induction of Dynamin 2. Likewise, radiation-induced viral gene transfer in these cells (6.5-, 5.5-, and 9.0-fold, respectively) was significantly reduced in siRNA-transfected cells (2.7-, 3.7-, and 5.0-fold, respectively). Moreover, viral uptake in LoVo tumor xenografts was significantly increased in s.c. tumors (10.9-fold) when adenovirus was given i.v. at 24 hours after tumor irradiation, coincident with an elevated Dynamin 2 expression in irradiated tumors. These data suggest that ionizing radiation induces adenovirus gene transfer in cells and tumor xenografts by regulating viral uptake, potentially through interaction with cellular Dynamin 2 and thus should provide insight into improving adenovirus targeting in tumors.
Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials
Authors: J.W. Valle, J. Furuse, M. Jitlal, S. Beare, N. Mizuno, H. Wasan, J. Bridgewater, T. Okusaka
Journal: Annals of Oncology (2013)

Two recent studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone for patients with pathologically proven advanced biliary tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). This pre-planned analysis evaluates the efficacy of CisGem with increased statistical power.
Ex Vivo Antisense Oligonucleotides to Proliferating Cell Nuclear Antigen and Cdc2 Kinase Inhibit Graft Coronary Artery Disease
Authors: D. N. Miniati, E. G. Hoyt, B. T. Feeley, R. S. Poston, R. C. Robbins
Journal: Circulation (2000)

The long-term success of cardiac transplantation is limited by graft coronary artery disease (GCAD). Antisense oligonucleotides (ASs) to proliferating cell nuclear antigen (PCNA) and Cdc2 kinase (Cdc2 k) can arrest cell cycle progression and inhibit neointimal hyperplasia. Transforming growth factor-ss(1) (TGF-ss(1)) has been implicated in vascular smooth muscle cell (VSMC) activation. The role of TGF-ss(1) in GCAD remains unclear. We hypothesized that ASs to PCNA and Cdc2 k would inhibit VSMC proliferation and GCAD.In vitro VSMC proliferation was determined after pretreatment with AS solution or medium alone followed by angiotensin II stimulation. PVG-to-ACI rat heterotopic cardiac transplantation procedures were performed after ex vivo pressure-mediated transfection of ASs to PCNA and Cdc2k or saline alone. At postoperative days 30, 60, and 90, allografts were assessed for GCAD, percent neointimal macrophages and VSMCs, and TGF-ss(1) activity. AS pretreatment significantly attenuated VSMC proliferation. At postoperative day 90, percent affected arteries, percent occlusion, and intima-media ratio demonstrated severe GCAD in saline-treated allografts, whereas these parameters were significantly lower in AS-treated allografts. Percent neointimal macrophages and VSMCs was reduced in AS-treated allografts. TGF-ss(1) activity was increased in saline compared with AS-treated allografts and nontransplanted heart controls.ASs to PCNA and Cdc2 k inhibit VSMC proliferation in vitro and reduce GCAD, percent neointimal VSMCs and macrophages, and TGF-ss(1) activity in vivo. TGF-ss(1) may play a "response to injury" role in the development of GCAD. The prevention of GCAD via AS inhibition of cell cycle regulatory genes before reperfusion may offer a useful clinical alternative to current therapeutic strategies.
Cholangiocarcinoma arising after biliary-enteric drainage procedures for benign disease
Authors: V Bettschart, R A E Clayton, R W Parks, O J Garden, C O C Bellamy
Journal: Gut (2002)

Although choledochoduodenostomy was widely performed for choledocholithiasis in the 1960s and 1970s, Roux-en-Y hepaticojejunostomy is currently the preferred biliary-enteric anastomosis for benign and malignant disease and is generally considered a low risk procedure, aside from the potential for cholangitis.

We report three cases referred over a 12 month period in which cholangiocarcinoma developed after previous biliary-enteric anastomosis, and review the literature to determine the likelihood of an association.

### Case No 1

A 51 year old female developed obstructive jaundice 26 years after choledochoduodenostomy for a biliary stricture after iatrogenic bile duct injury. Endoscopic retrograde cholangiopancreatography (ERCP) showed neoplastic infiltration at the level of the anastomosis, biopsy of which revealed cholangiocarcinoma …
Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.
Authors: F B Taylor, A Chang, C T Esmon, A D'Angelo, S Vigano-D'Angelo, K E Blick
Journal: Journal of Clinical Investigation (1987)

Gram-negative septicemia elicits multiple abnormalities of the coagulation system. Although products of coagulation can lead to clot formation, thereby potentiating organ damage, recent work has shown that low concentrations of thrombin can protect animals from the shock state. Because these amounts of thrombin also lead to formation in vivo of the anticoagulant enzyme, activated protein C, we examined the role of protein C in modulation of Escherichia coli shock in baboons. First, we infused activated protein C and lethal concentrations of E. coli organisms, which prevented the coagulopathic, hepatotoxic, and lethal effects of E. coli. Second, using an antibody to protein C we blocked protein C activation in vivo to determine if this influenced the response to lethal and sublethal concentrations of E. coli organisms. Under these conditions the response to lethal concentrations of E. coli organisms was made more severe and the response to sublethal concentrations of E. coli was made lethal. The coagulopathic, hepatotoxic, and lethal responses in this latter case were prevented by infusion of exogenous protein C.
Pemetrexed and Cisplatin for Malignant Pleural Mesothelioma: A New Standard of Care?
Authors: Valerie W. Rusch
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.02.043 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12860935 Pemetrexed and Cisplatin for Malignant Pleural Mesothelioma: A New Standard of Care? Valerie W. RuschxValerie W. RuschSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2003.02.043 Full Text PDF Figures and Tables "Pemetrexed and Cisplatin for Malignant Pleural Mesothelioma: A New Standard of Care?." Journal of Clinical Oncology, 21(14), pp. 2629–2630© 2003 by American Society of Clinical Oncology
511 LIVER MESENCHYMAL CELLS CONTRIBUTE TO IMPROVEMENT OF HUMAN CRYOPRESERVED HEPATOCYTES SURVIVAL AND FUNCTION
Authors: A.-C. Dusabineza, D. Ngoc Khuu, L. Dollé, J. Abarca-Quinones, E. Sokal, L.A. van Grunsven, M. Najimi, I.A. Leclercq
Journal: Journal of Hepatology (2011)
Angiotensin II Increases Parathyroid Hormone-Related Protein (PTHrP) and the Type 1 PTH/PTHrP Receptor in the Kidney
Authors: Oscar Lorenzo, Marta Ruiz-Ortega, Pedro Esbrit, Mönica Rupérez, Arantxa Ortega, Soledad Santos, Julia Blanco, Luis Ortega, Jesus Egido
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Angiotensin II (AngII) participates in the pathogenesis of kidney damage. Parathyroid hormone (PTH)–related protein (PTHrP), a vasodilator and mitogenic agent, is upregulated during renal injury. The aim of this study was to investigate the potential relation between AngII and PTHrP system in the kidney. Different methods were used to find that both rat mesangial and mouse tubuloepithelial cells express PTHrP and the type 1 PTH/PTHrP receptor (PTH1R). In these cells, AngII increased PTHrP mRNA and protein production. In contrast, PTH1R mRNA was increased in mesangial cells and downregulated in tubular cells, but its protein levels were unmodified in both cells. AT1 antagonist, but not AT2, abolished AngII effects on PTHrP/PTH1R. The in vivo effect of AngII was further investigated by systemic infusion (a low dose of 50 ng/kg per min) into normal rats. In controls, PTHrP immunostaining was mainly detected in renal tubules. In AngII-infused rats, PTHrP staining increased in renal tubules and appeared in the glomerulus and the renal vessels. After AngII infusion, PTHR1 staining was markedly increased in all these renal structures at day 3 but remained elevated only in tubules at day 7. The AT1 antagonist, but not the AT2, significantly diminished AngII-induced PTHrP and PTHR1 overexpression in the renal tissue, associated with a decrease in tubular damage and fibrosis. The results indicate that AngII regulates renal PTHrP/PTH1R system via AT1 receptors. These findings demonstrate that PTHrP upregulation occurs in association with the mechanisms of AngII-induced kidney injury.
Siliceous Dust in Relation to Pulmonary Disease Among Miners in the Joplin District, Missouri.
Authors: Edwin Higgins, A. J. Lanza, F. B. Laney, George S. Rice
Journal: JAMA (1918)

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PHASE I INDIVIDUAL DOSE TITRATION TRIAL OF THE HUMAN CORTICOTROPIN-RELEASING FACTOR (HCRF), CORTICORELIN ACETATE INJECTION (XERECEPT) IN PEDIATRIC PATIENTS WITH PERITUMORAL EDEMA OF THE BRAIN
Authors: S. Goldman, J. Fangusaro, R. Lulla, S. Chi, P. Manley, N. Robison, H.-A. Kroon, M. Kieran
Journal: Neuro-Oncology (2014)

BACKGROUND: Steroid induced toxicities adversely affect the quality of life of children treated with brain tumors. Side effects include; mood changes, myopathy, weight gain, fluid retention, hypertension, moon faces, acne, etc. Alternatives to control peritumoral edema are needed. METHODS: Eligible patients included Pediatric patients less than 18 years of age on chronic corticosteroids who failed attempts to wean. A two part trial consisting of a Phase I dose escalation phase followed by a long-term (26 week) maintenance phase was undertaken. Patients were initially enrolled at a dose of 10 ug/kg divided BID, and in the absence of DLTs, were escalated to 20 ug/kg/day, 30 ug/kg/day, 40 ug/ kg/day and 60ug/kg/day of Xereceptw. If no DLT's were observed in cohorts of 3 subjects, subsequent patients were started at the next highest dose level with a plan to assess twelve patients at the highest tolerated dose. The study was designed to evaluate: toxicities of Xerecept, dexamethasone dose reduction, changes in steroid induced side effects and HRQoL. Dexamethasone dose reduction was allowed beginning after 7 days of Xerecept. RESULTS: 15 subjects were enrolled, 14 evaluable patients with recurrent DIPG(8), HGG (4) and ependymoma (2) received Xerecept. No patients experienced a DLT. All evaluable patients were able able to reduce dexamethasone. From a mean starting dose of 5.4 mg/day to a minimal dose of 1 mg/day in 87.5% of patients on treatment for at least 6 weeks. 4 patients weaned off completely despite progressive disease. QOL analysis revealed significant improvements in physical functioning, emotional functioning, and improvements in sleep/rest and fatigue scores for all evaluable patients at week 18. CONCLUSIONS: Xerecept at 60 ug/kg/day is safe and well tolerated. Even in this poor prognosis population, significant dose reduction of corticosteroids can occur with Xerecept. Patient QOL improved as evident by changes in emotional, physical and fatigue scores. Future efficacy trials with Xerecept are warranted, a Phase II/III trial is planned. SECONDARY CATEGORY: Pediatrics.
Boca was the most predominant virus among asymptomatic preschools in a surveillance (2010-2011) in Greece
Authors: Doxa Kotzia, Christine Kottaridi, Apostolis Giotas, Constantinos Douros, Andreas Fretzayas, Petros Karakitsos, Konstantinos N. Priftis
Journal: European Respiratory Journal (2014)

Aims: The majority of preschoolers attend daycare centers but an increased incidence of respiratory infections in this group due to higher exposure to other children has been observed. The aim was to examine the in incidence of respiratory virus detection among asymptomatic daycare attending children.

Methods: The study population consisted of 233 preschool aged children, attending nursery: 120 living in a rural area with low air-pollution (Viotia) and 113 in a metropolitan city (Athens). Nasal-pharyngeal swabs (NPS) were collected for 4 consecutive time periods during the school year December 2010 – June 2011 and examined with RT-PCR for Adenovirus, Bocavirus, Coronavirus, Enteroviruses, Influenza (A, B, C) viruses, Metapneumovirus, Parainfluenza (1, 2, 3, 4) viruses, Rhinovirus, and RSV (A, B). Children were generally well during the sampling period, with few of them having minor coryzal symptoms. Fisher's exact test was used.

Results: In the 1st, 2nd, 3rd, and 4th sampling period, Bocavirus (71/233) and Adenovirus (12/233), RSV (41/233) and Bocavirus (32/233), Bocavirus (36/233) and RSV (18/233), and Rhinovirus (37/233) and Bocavirus (36/233) were the most prevalent respectively.

Bocavirus was isolated 4, 3, and 2 times from 4, 13, and 36 children, respectively. RSV isolated 3 and 2 times from 2 and 8 children, respectively. Rhinovirus isolated 3 and 2 times from 2 and 19 children, respectively, whereas adenovirus isolated 2 times only from 1 child.

Consclusions: Boca virus was among the two most prevalent viruses as well as the most repeatedly isolated virus from the same child in NPS of asymptomatic preschoolers' during the 2010-2011 school-period.
Mechanisms of Glucose Lowering of Dipeptidyl Peptidase-4 Inhibitor Sitagliptin When Used Alone or With Metformin in Type 2 Diabetes
Authors: Carolina Solis-Herrera, Curtis Triplitt, Jose de Jesús Garduno-Garcia, John Adams, Ralph A. DeFronzo, Eugenio Cersosimo
Journal: Diabetes Care (2013)

To assess glucose-lowering mechanisms of sitagliptin (S), metformin (M), and the two combined (M+S).We randomized 16 patients with type 2 diabetes mellitus (T2DM) to four 6-week treatments with placebo (P), M, S, and M+S. After each period, subjects received a 6-h meal tolerance test (MTT) with [(14)C]glucose to calculate glucose kinetics. Fasting plasma glucose (FPG), fasting plasma insulin, C-peptide (insulin secretory rate [ISR]), fasting plasma glucagon, and bioactive glucagon-like peptide (GLP-1) and gastrointestinal insulinotropic peptide (GIP) were measured.FPG decreased from P, 160 ± 4 to M, 150 ± 4; S, 154 ± 4; and M+S, 125 ± 3 mg/dL. Mean post-MTT plasma glucose decreased from P, 207 ± 5 to M, 191 ± 4; S, 195 ± 4; and M+S, 161 ± 3 mg/dL (P < 0.01). The increase in mean post-MTT plasma insulin and in ISR was similar in P, M, and S and slightly greater in M+S. Fasting plasma glucagon was equal (≈ 65-75 pg/mL) with all treatments, but there was a significant drop during the initial 120 min with S 24% and M+S 34% (both P < 0.05) vs. P 17% and M 16%. Fasting and mean post-MTT plasma bioactive GLP-1 were higher (P < 0.01) after S and M+S vs. M and P. Basal endogenous glucose production (EGP) fell from P 2.0 ± 0.1 to S 1.8 ± 0.1 mg/kg · min, M 1.8 ± 0.2 mg/kg · min (both P < 0.05 vs. P), and M+S 1.5 ± 0.1 mg/kg · min (P < 0.01 vs. P). Although the EGP slope of decline was faster in M and M+S vs. S, all had comparable greater post-MTT EGP inhibition vs. P (P < 0.05).M+S combined produce additive effects to 1) reduce FPG and postmeal plasma glucose, 2) augment GLP-1 secretion and β-cell function, 3) decrease plasma glucagon, and 4) inhibit fasting and postmeal EGP compared with M or S monotherapy.
Electronic Health Records: Just around the Corner? Or over the Cliff?
Authors: Richard J. Baron, Elizabeth L. Fabens, Melissa Schiffman, Erica Wolf
Journal: Annals of Internal Medicine (2005)

We recently implemented a full-featured electronic health record in our independent, 4-internist, community-based practice of general internal medicine. We encountered various challenges, some unexpected, in moving from paper to computer. This article describes the effects that use of electronic health records has had on our finances, work flow, and office environment. Its financial impact is not clearly positive; work flows were substantially disrupted; and the quality of the office environment initially deteriorated greatly for staff, physicians, and patients. That said, none of us would go back to paper health records, and all of us find that the technology helps us to better meet patient expectations, expedites many tedious work processes (such as prescription writing and creation of chart notes), and creates new ways in which we can improve the health of our patients. Five broad issues must be addressed to promote successful implementation of electronic health records in a small office: financing; interoperability, standardization, and connectivity of clinical information systems; help with redesign of work flow; technical support and training; and help with change management. We hope that sharing our experience can better prepare others who plan to implement electronic health records and inform policymakers on the strategies needed for success in the small practice environment.