tbuckley/cabot-search huggingface dataset:
Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms.
Authors: A M Senderowicz, D Headlee, S F Stinson, R M Lush, N Kalil, L Villalba, K Hill, S M Steinberg, W D Figg, A Tompkins, S G Arbuck, E A Sausville
Journal: Journal of Clinical Oncology (1998)

PURPOSE We conducted a phase I trial of the cyclin-dependent kinase inhibitor, flavopiridol (National Service Center [NSC] 649890), to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacology of flavopiridol given as a 72-hour infusion every 2 weeks. PATIENTS AND METHODS Seventy-six patients with refractory malignancies with prior disease progression were treated with flavopiridol, with first-cycle pharmacokinetic sampling. RESULTS Forty-nine patients defined our first MTD, 50 mg/m2/d x 3 with dose-limiting toxicity (DLT) of secretory diarrhea at 62.5 mg/kg/d x 3. Subsequent patients received antidiarrheal prophylaxis (ADP) to define a second MTD, 78 mg/m2/d x 3 with DLT of hypotension at 98 mg/m2/d x 3. Other toxicities included a proinflammatory syndrome with alterations in acute-phase reactants, particularly at doses &gt;50 mg/ m2/d x 3, which in some patients prevented chronic therapy every 2 weeks. In some patients, ADP was not successful, requiring dose-deescalation. Although approximately 70% of patients displayed predictable flavopiridol pharmacology, we observed unexpected interpatient variability and postinfusion peaks in approximately 30% of cases. At the two MTDs, we achieved a mean plasma flavopiridol concentration of 271 nM (50 mg/m2/d x 3) and 344 nM (78 mg/m2/d x 3), respectively. One partial response in a patient with renal cancer and minor responses (n=3) in patients with non-Hodgkin's lymphoma, colon, and renal cancer occurred. CONCLUSION The MTD of infusional flavopiridol is 50 mg/m2/d x 3 with dose-limiting secretory diarrhea at 62.5 mg/m2/d x 3. With ADP, 78 mg/m2/d x 3 was the MTD, with dose-limiting hypotension at 98 mg/m2/d x 3. Based on chronic tolerability, 50 mg/m2/d x 3 is the recommended phase II dose without ADP. Antitumor effect was observed in certain patients with renal, prostate, and colon cancer, and non-Hodgkin's lymphoma. Concentrations of flavopiridol (200 to 400 nM) needed for cyclin-dependent kinase inhibition in preclinical models were achieved safely.
A new peripherally implanted subcutaneous permanent central venous access device for patients requiring chemotherapy.
Authors: R R Salem, B A Ward, T S Ravikumar
Journal: Journal of Clinical Oncology (1993)

A peripherally implanted central venous access device (P.A.S. Port; Pharmacia Deltec Inc, St Paul, MN) was evaluated for ease of insertion, functionality, acceptance, and complications in patients who required long-term venous access. A hand-held tracking system (Cath-Finder; Pharmacia Deltec Inc) used to determine catheter tip location was also evaluated.A P.A.S. Port was placed in 47 patients who required long-term intravenous access. The median follow-up duration has been 32 weeks (range, 2 to 112). Total usage has been 2,028 catheter-weeks. The Cath-Finder was used to determine catheter tip location during insertion. Nursing staff and patient satisfaction were polled and functionality and complications were recorded.The device was found to be simple to insert, the procedure well tolerated, and, with one exception, the Cath-Finder accurately predicted catheter tip location. There was a 6.4% incidence of transient phlebitis and a 6.4% incidence of symptomatic axillary or subclavian vein thrombosis. There were no infectious complications. Access was simple in all but two obese patients. The device functioned well in all patients, except three in whom blood aspiration was difficult and two in whom fluid administration was slow. The device was well tolerated by all patients and nursing staff satisfaction was high.This device provides a highly acceptable, additional method of implantable, permanent central venous access for chemotherapy patients with a low complication rate. The successful use of the Cath-Finder and minor extent of the procedure may allow this device to be inserted in a clinic procedure room without sedation and fluoroscopy.
Elastic band ligation for the removal of a colonic tubular adenoma in a diverticulum
Authors: Joana Carmo, Susana Marques, Iolanda Chapim, Pedro Barreiro, Miguel Bispo, Cristina Chagas
Journal: Endoscopy (2015)

A 56-year-old healthy patient underwent colonoscopy after a positive fecal occult blood test result. This examination showed diverticulosis of the left side of the colon and, at 20 cm from the anal verge, a 6-mm sessile polyp in the neck of a diverticulum with intradiverticular extension ([Fig. 1 a]). Narrow-band imaging showed a large tubular pit pattern: Kudo type III-L ([Fig. 1 b]).
Miliary tuberculosis: About 16 cases
Authors: Fatma Chermiti Ben Abdallah, Ghada Ben Ali, Ridha Mahouachi, Amel Chtourou, Sofia Taktak, Ali Ben Kheder
Journal: European Respiratory Journal (2011)

Introduction:  Miliary tuberculosis (MT) is a rare and severe form of tuberculosis (TB) due to hematogenous dissemination of tuberculosis bacillus (BK).   Aim:  Describe radio-clinical and biological presentation of MT ant to identify prognostic factors in comparison with pulmonary TB.   Method:  Retrospective comparative study including a group of MT and a group of pulmonary TB. The diagnostic criteria were radiological for definition of miliary and bacteriological or histological for TB.   Results:  16 cases of MT and 41 patients with pulmonary TB (control group) were included. Mean age was 48.3±22 years. Compared to pulmonary TB, we note that MT was more significantly associated with bad economic conditions, dyspnea, crackles, absence of night sweats and negativity of tuberculosis skin test. Presence of mediastinal lymphadenopathies, absence of excavation or other images, extra pulmonary localizations especially liver and lymph node and hyponatremia were also more significantly observed in MT. The analysis of the results had identified some mortality predictive factors such as the presence of night sweats, hepatic cytolysis, high sedimentation rate and the presence of excavations in the roentgenogram.   Conclusion:  MT is a severe form of TB. The presence of night sweats, hepatic cytolysis, accelerated sedimentation rate and presence of excavation in the chest radiograph are predictive of poorer prognosis.
Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects
Authors: D C Goff, D C Henderson, E Amico
Journal: American Journal of Psychiatry (1992)

The authors' goal was to study the relationship between smoking status and clinical characteristics in schizophrenic patients.Seventy-eight schizophrenic outpatients were assessed by a single rater using the Brief Psychiatric Rating Scale (BPRS), the Abnormal Involuntary Movement Scale, and the Simpson-Angus Scale for extrapyramidal symptoms. Current smokers (N = 58) were compared with nonsmokers (N = 20) on clinical variables by independent t tests and chi-square tests. Differences in outcome variables were tested by multiple analysis of covariance (ANCOVA) with smoking status and gender as factors and age, neuroleptic dose, and caffeine consumption as covariates.Seventy-four percent of patients were current smokers and reported a mean of 19 cigarettes smoked per day. Compared to nonsmokers, current smokers were significantly more likely to be men, to be younger, and to have had an earlier age at onset and a greater number of previous hospitalizations. Current smokers and nonsmokers received mean neuroleptic doses of 1160 and 542 mg/day (chlorpromazine equivalents); the difference was significant. Current smokers also displayed significantly less parkinsonism and more akathisia and had higher total scores on the BPRS. Overall multiple ANCOVA demonstrated a significant main effect for smoking status but not gender or the interaction between gender and smoking status. Univariate ANCOVAs demonstrated a significant main effect of smoking status only for the Simpson-Angus Scale score.Cigarette smokers receive significantly higher neuroleptic doses, in part because of a smoking-induced increase in neuroleptic metabolism. Smoking is also associated with significant reduction in levels of parkinsonism. Smoking status is a significant factor that should be considered in assessment of neuroleptic dose requirements and neuroleptic side effects.
Randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric (OG) cancer: The REAL 2 trial
Authors: D. Cunningham, S. Rao, N. Starling, T. Iveson, M. Nicolson, F. Coxon, G. Middleton, F. Daniel, J. Oates, A. R. Norman
Journal: Journal of Clinical Oncology (2006)

LBA4017 Background: The aim was to establish the potential use of the third generation platinum compound, oxaliplatin (O) &amp; the oral fluoropyrimidine capecitabine (X) in untreated patients (pts) with advanced OG cancer. Methods: After stratification for PS and extent of disease, pts with histologically confirmed adenocarcinoma, squamous or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction or stomach were randomised, in a 2 x 2 design, to 1 of 4 regimens; epirubicin, cisplatin, fluorouracil (ECF), EOF, ECX or EOX. Doses E 50 mg/m 2 , C 60 mg/m 2 &amp; O 130 mg/m 2 IV 3 weekly; F 200 mg/m 2 IV daily &amp; X 625 mg/m 2 twice daily PO continuously; for 8 cycles. The primary endpoint was overall survival. With 1000 pts (250 per arm) the study had 80% power to demonstrate non-inferiority of X over F and also O over C if the upper limit of the HR 95% CI excluded 1.23 (α = 0.05) in the per protocol population. Analysis was performed using the logrank test and Cox regression analysis. Results: 1002 pts were randomised from 61 centres. Demographics were balanced, 89% were PS 0–1, 77% metastatic, median age 63 (range 22–83), 81% were male and 40% gastric primaries. Histology: adenocarcinoma in 88% and 52% poorly differentiated. 11 pts were ineligible and 27 pts were withdrawn before treatment commenced. Median follow up was 17.1 months and 850 events have occurred. There were no significant differences in response rates comparing ECF to, EOF, ECX and EOX (41%, 42%, 46%, and 48% respectively); grade 3–4 non haematological toxicity 36%, 42%, 33% and 45%; and grade 3–4 neutropaenia 42%, 30% (p = 0.008), 51% (p = 0.043) and 28% (p = 0.001) respectively. Conclusions: Capecitabine may replace 5FU and Oxaliplatin may replace Cisplatin in triplet regimens used for the treatment of advanced OG cancer. [Table: see text] [Table: see text]
Bone Marrow and Peripheral Blood Dendritic Cells From Patients With Multiple Myeloma Are Phenotypically and Functionally Normal Despite the Detection of Kaposi’s Sarcoma Herpesvirus Gene Sequences
Authors: Noopur Raje, Jianlin Gong, Dharminder Chauhan, Gerrard Teoh, David Avigan, Zekui Wu, Dongshu Chen, Steven P. Treon, Iain J. Webb, Donald W. Kufe, Kenneth C. Anderson
Journal: Blood (1999)
Abstract 19176: In-hospital Outcomes of Unstable Angina in Patients with Chronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD), Years 2005-2011
Authors: Chaudhry M Sarwar, Shasank Rijal, Yasir Akram, Aqib H Malik, Malik M Adil, Fahad Saeed
Journal: Circulation (2014)

Background: Unstable angina (UA) is prevalent in patients with Chronic Kidney Disease (CKD)including End Stage Renal Disease (ESRD) requiring dialysis. Outcomes of UA in these patients are largely unknown. We sought to compare the in-hospital outcomes among the patients with CKD and ESRD admitted with UA. Methods: We used data from the National Inpatient Sample (NIS) from 2005 to 2011 with the primary discharge diagnosis of UA and the secondary diagnosis of CKD and ESRD. The associations of CKD and ESRD with, in-hospital complications and procedures, discharge outcomes and mortality were explored after adjusting for potential confounders using logistic regression analyses. Results: Of the 541,948 patients admitted with unstable angina, 17230 (3.17%) had Renal disease (CKD and ESRD). ESRD was present in 4683 (27.18%) patients while 12547 (72.82) patients had CKD. In-hospital complications; deep venous thrombosis (1.4% vs. 0.2%; p<0.002) and sepsis (1.1% vs. 0.1%; p<0.002) were significantly higher in patie...
Histamine and its Release from Nasal Polyps: Preliminary Communication
Authors: A B Drake-Lee
Journal: Journal of the Royal Society of Medicine (1984)

Two hundred consecutive patients admitted for polypectomy had no evidence of an increased incidence of allergic disorders. Mast cell degranulation was found on transmission electron microscopy and this resulted in considerable quantities of histamine in polyp extracellular fluid (124–7300 ng/ml). RAST levels of allergen-specific IgE to house-dust mite and mixed-grass pollens were raised in 4 out of 28 cases in polyp fluid, and in only one matched serum. In vitro challenge of polyp tissue with allergen extract and anti-IgE suggested an IgE-mediated response in only 4 of 36 patients.
Effect of Pindolol on Stress-Related Disturbances of Musical Performance: Preliminary Communication<sup>1</sup>
Authors: I M James, W Burgoyne, I Temple Savage
Journal: Journal of the Royal Society of Medicine (1983)

The effect of 5 mg pindolol on stress-induced disturbances of performance were assessed in 30 professional musicians. An overall inverse relationship was found between anxiety and musical performance. Reduction in anxiety by administration of pindolol was associated with a subjective improvement in performance. A stress-related tachycardia and increase in systolic blood pressure were attenuated. Pindolol had no effect on peak flow measurements.
Severe life stress as a predictor of early disease progression in HIV infection
Authors: D L Evans, J Leserman, D O Perkins, R A Stern, C Murphy, B Zheng, D Gettes, J A Longmate, S G Silva, C M van der Horst, C D Hall, J D Folds, R N Golden, J M Petitto
Journal: American Journal of Psychiatry (1997)

Although there is evidence that stress is associated with alterations in immunity, the role of emotional factors in the onset and course of immune-based diseases such as cancer and AIDS has not been established. This prospective study was designed to test the hypothesis that stressful life events accelerate the course of HIV disease.Ninety-three HIV-positive homosexual men who were without clinical symptoms at the time of entry into the study were studied for up to 42 months. Subjects received comprehensive medical, neurological, neuropsychological, and psychiatric assessments every 6 months, including assessment of stressful life events during the preceding 6-month interval. Several statistical approaches were used to assess the relation between stress and disease progression.The time of the first disease progression was analyzed with a proportional hazard survival method, which demonstrated that the more severe the life stress experienced, the greater the risk of early HIV disease progression. Specifically, for every one severe stress per 6-month study interval, the risk of early disease progression was doubled. Among a subset of 66 subjects who had been in the study for at least 24 months, logistic regression analyses showed that higher severe life stress increased the odds of developing HIV disease progression nearly fourfold. the degree of disease progression was also predicted by severe life stress when a proportional odds logistic regression model was used for analysis.This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression.
Abstract 17221: AMPK Regulation of Microtubule Dynamics in Cardiac Hypertrophy
Authors: John T Fassett, Xin Xu, Zhongbing Lu, Xinli Hu, Ping Zhang, Yingjie Chen, Robert Bache
Journal: Circulation (2011)

Cardiomyocyte hypertrophy requires increased protein synthesis as well as remodeling/growth of the cytoskeletal networks necessary to support cell enlargement. AMPK is a metabolic sensor that couples cell growth to ATP levels. Whether AMPK regulates cardiomyocyte cytoskeletal dynamics and how this influences hypertrophy is not known. Here we used cultured neonatal cardiomyocytes and AMPK KO mice to examine the role of AMPK in cytoskeletal remodeling that occurs during hypertrophy. In cardiomyocytes exposed to hypertrophic stress (phenylephrine or constitutively active Raf), AMPK activation (AICAR 0.1-0.2 mM) or constitutively active AMPK had little effect on intermediate filaments or myofilaments, but did attenuate accumulation and stabilization of microtubules (AICAR reduced MT levels to 38% +/- 3.6 % and detyrosinated MTs to 14% +/- 11% of PE treated; p&lt;.001). Importantly, AMPK reduction of microtubule stability occurred at low doses of AICAR that did not block mTOR/p70S6k signaling or translation, suggesting microtubule dynamics are an extremely sensitive target of AMPK. Interestingly, AMPK reduction of microtubules limited cardiomyocyte elongation, suggesting a mechanism by which AMPK influences cell morphology. In mice exposed to pressure overload (transverse aortic constriction;TAC), microtubule levels were exacerbated by AMPK alpha 2 KO as compared to WT mice (202 % +/- 42%; p=.047). Furthermore, microtubule levels exhibited a significant inverse correlation with LV ejection fraction (R 2 =.752; p&lt;.001), suggesting microtubule densification may contribute to reduced contractile function in AMPK KO mice. Mechanistically, AMPK activation increased phosphorylation of Microtubule Associated Protein 4 (MAP4) at serine 768, which prevents its ability to stabilize microtubules. Phosphorylation of MAP4 Ser768 was reduced in AMPK KO mice, but increased in WT mice exposed to metformin, which also reduced MT stability. RNAi depletion of MAP4 in isolated cardiomyocytes further confirmed its important role in stabilizing microtubules during hypertrophy. Together, our data identify a novel protective role for AMPK in preventing aberrant stabilization and accumulation of cardiac microtubules in response to hypertrophic stress.
Baseline left ventricular d<i>P</i>/d<i>t</i><sub>max</sub> rather than the acute improvement in d<i>P</i>/d<i>t</i><sub>max</sub> predicts clinical outcome in patients with cardiac resynchronization therapy
Authors: Margot D. Bogaard, Patrick Houthuizen, Frank A. Bracke, Pieter A. Doevendans, Frits W. Prinzen, Mathias Meine, Berry M. van Gelder
Journal: European Journal of Heart Failure (2011)
Performance and impact of a rapid method combining mass spectrometry and direct antimicrobial susceptibility testing on treatment adequacy of patients with ventilator-associated pneumonia
Authors: M. Le Dorze, N. Gault, A. Foucrier, E. Ruppé, B. Mourvillier, P.L. Woerther, G. Birgand, P. Montravers, M.P. Dilly, F. Tubach, A. Andremont, J.F. Timsit, M. Wolff, L. Armand-Lefèvre
Journal: Clinical Microbiology and Infection (2014)
Outcomes and complications of bronchoscopy-guided percutaneous dilatational tracheostomy
Authors: Jose Andres García Romero de Tejada, Rosa Mar Gόmez Punter, Ian Carrasco Barber, Ricardo Andino Ruiz, Javier Aspa Marco, Olga Rajas Naranjo
Journal: European Respiratory Journal (2011)

Background:  Percutaneous tracheostomy (PT) is one of the most frequently performed procedures in Intensive Care Unit (ICU). As many as 10% of patients requiring at least 3 days of mechanical ventilation will receive a tracheostomy. Some of the complications can be severe and can be prevented with bronchoscopic-assistance.   Aim:  To investigate the outcome and complications of bronchoscopy-guided PT.   Material and methods:  59 patients was prospectively included from March-November/2010. Demographic data, time of procedure and complications were studied. Patient9s heart rate, blood pressure and continuous pulse oximetry were monitored. All PT were performed under bronchoscopic control at the patient9s bedside in the ICU by an medical intensivist and a pulmonologist. Statistical software Sigma-Stat 3.5 was used.   Results:  54% of patients: male. Patient mean age: 60. Mean body mass index: 25.2 (Standar Error Mean-SEM 0.5). Mean APACHE index: 20.1. SAPS: 44.5. The reason for admission at ICU was due to medical conditions (70%) and surgical/polytraumatism (30%). Indication for PT: coma (47%), intubation weaning failure (34%), neuromuscular failure (9.4%) and prolongued endotracheal intubation (9,4%). Mean duration of PT: 3.5 mn. Main complications: O 2  desaturation    Conclusions:  PT is a safe technique. The use of bronchocospy reduces duration of procedure, decreases morbidity and can identify complications missed by a “blind” approach.
Abstract 2641: Plasma Von Willebrand Factor and ADAMTS13 Concentrations in Atrial Fibrillation
Authors: Takashi Uemura, Koichi Kaikita, Hiroshige Yamabe, Masakazu Matsukawa, Kenji Soejima, Yasuaki Tanaka, Kenji Morihisa, Hisao Ogawa
Journal: Circulation (2007)

Background : Von Willebrand factor (VWF) is released from damaged endothelium, and has a role in platelet aggregation through a receptor on the platelet surface. A metalloprotease that cleaves VWF multimers has been identified, namely, ADAMTS13. We recently reported that the serial changes in plasma VWF and ADAMTS13 antigen levels in patients with acute myocardial infarction (AMI), and that the VWF/ADAMTS13 ratio was a useful prognostic indicator of long-term thrombotic events after AMI. Although previous studies have shown raised plasma VWF in patients with atrial fibrillation (AF), little is known about the role of ADAMTS13 in the pathogenesis of AF. In the present study, we examined the relation between VWF and ADAMTS13 in AF patients. Methods and Results : We measured the plasma VWF and ADAMTS13 antigen levels by ELISA in 45 AF patients and 49 control subjects, and also performed echocardiography to examine the relations between these markers and left atrial or ventricular functions. The plasma VWF antigen levels were significantly higher in AF patients compared with controls (2017±749 vs. 1504±497 mU/ml, P=0.0002). In contrast, the plasma ADAMTS13 antigen levels were significantly lower in AF patients compared with controls (825±181 vs. 911±193 mU/ml, P=0.03). The VWF/ADAMTS13 ratio was significantly higher in AF patients compared with controls (2.59±1.20 vs. 1.75±0.76, P&lt;0.0001). The number of patients who received aspirin and warfarin was significantly higher in AF group than control subjects, however, those medical therapy did not affect the VWF and ADAMTS13 antigen levels. There was significant positive correlation between VWF antigen levels and the left atrial dimension (n=128, r=0.228, P=0.0095). Furthermore, there was significant negative correlation between VWF antigen levels and the left atrial appendage peak flow velocity measured by transesophageal echocardiography (n=23, r=-0.611, p=0.0015). Conclusions : These findings suggest that the balance between VWF and ADAMTS13 levels may play an important role in the intra-atrial thrombus formation in AF patients. The present results would open a new therapeutic target for prevention of thromboembolic complications in AF.