tbuckley/cabot-search huggingface dataset:
Neutrophil response kinetics after G-CSF and Peg-G-CSF usage post chemotherapy
Authors: D. Pendharkar, S. Gupta, T. Rashid
Journal: Journal of Clinical Oncology (2008)

20708 Background: G-CSF is recommended for prophylaxis of Neutropenia post chemotherapy. The dosing is limited to days required to reach target value of ANC. It is still not clear as what are the individual variations in dosing and requirement. With peg G-CSF it is single administration. Aim of this analysis was to study the neutrophil kinetics after institution of G-CSF and Peg-G-CSF post chemotherapy. Methods: Patients undergoing chemotherapy were enrolled in the trial. Eligibility criteria included ANC of less than 1,000/mm3 in index cycle. Three subsequent cycles of same chemotherapy was given with G-CSF (filgrastim 300 mcg) support. G-CSF was used till ANC reached > 10,000/mm3. In peg-G-CSF group single injection was used. Data from 75 events in G-CSF and 33 events in Peg-G-CSF group were plotted to see individual variations between different cycles. Results: There were 36 evaluable patients in the study (25 in G-CSF and 11 in peg-G-CSF: 20 male, 16 female, age 18–74 years). In G-CSF group target ANC was reached in majority within 2–3 days. Only 2/25 patients took very long (7–9 days) in the first cycle. But in subsequent two cycles these two patients reached target value within 2–3 days. 3/25 patients took more than 2 days to target value post second cycle of chemotherapy. On day three when response was compared between three cycles, 10/25 patients had shown highest response after first usage. 5/25 -better response with every subsequent cycle 6/25 -highest response in middle cycle and 4/25 patients had similar response after every course of chemotherapy. If the response was less than 200% in first cycle in subsequent cycles the response remained at lower level. In peg-G-CSF group on day three 6/11 patients shown highest response after second usage, 4/11 after first usage and 1/11 showed better response with subsequent cycles. There was no correlation in neutrophil kinetics. Conclusions: Response to G-CSF and peg-filgrastim is varied at every usage. Time to neutrophil recovery will be different after each cycle of chemotherapy and it does not follow any kinetics. So there is a need to monitor WBC count with every usage of G-CSF in each chemotherapy cycle separately, for the target value. In poor responders during first usage may be there is a need to consider higher dosage next time or follow these patients more closely. No significant financial relationships to disclose.
Case 36-2009
Authors: Edwin Choy, Subba R. Digumarthy, Stephanie A. Koplin
Journal: New England Journal of Medicine (2009)

A 23-year-old man was transferred to this hospital because of cough, hoarseness, fever, and abnormalities on chest imaging. One month before admission, a nonproductive cough developed, followed by hoarseness, dyspnea on exertion, and fever. Imaging studies at another facility showed pulmonary and mediastinal masses and a lesion in the pelvis. Positron-emission tomographic scans obtained at this hospital showed 18F-fluorodeoxyglucose–avid lesions. A diagnostic procedure was performed.
Elevation of plasma concentrations of haloperidol after the addition of fluoxetine
Authors: D C Goff, K K Midha, A W Brotman, M Waites, R J Baldessarini
Journal: American Journal of Psychiatry (1991)

Fluoxetine (20 mg/day) was added for 7-10 days to stable doses of haloperidol given to eight psychotic patients. Mean plasma concentrations of haloperidol were elevated by 20% (p less than 0.05), but extrapyramidal side effects did not increase appreciably, indicating a relatively minor interaction between these agents.
Diagnostic Evaluation of Oral Glucose Tolerance Tests in Nondiabetic Subjects after Various Levels of Carbohydrate Intake
Authors: Hugh L. C. Wilkerson, Harris Hyman, Mildred Kaufman, Alvin C. McCuistion, John O'S. Francis
Journal: New England Journal of Medicine (1960)

IT is routine for most clinicians to instruct patients to take a high-carbohydrate diet for three days before a glucose tolerance test. Even with careful dietary instructions many patients find the suggested level of 250 to 300 gm. of carbohydrate in excess of their usual intake and have difficulty in consuming the amount of food required. In this study, an attempt is made to determine the effect of lower levels of carbohydrate intake on glucose tolerance in nondiabetic subjects, particularly regarding diagnostic evaluation.Since the time of Claude Bernard1 the concept of decreased glucose tolerance after starvation has been accepted. . . .
Abstract 190: Disruption of P90 Ribosomal S6 Kinase Binding 3 to Muscle A-kinase Anchoring Protein In Vivo Via Adeno-associated Virus Expression of a Competing Peptide Attenuates Pressure Overload-induced Cardiac Hypertrophy
Authors: CATHERINE L PASSARIELLO, Michael D Kritzer, Hrishikesh Thakur, Michael Sanders, Jinliang Li, Michael S Kapiloff
Journal: Circulation Research (2014)

RATIONALE: Cardiac myocyte hypertrophy is the main compensatory response to chronic stress in the heart. p90 ribosomal S6 kinase (RSK) family members are effectors for extracellular signal-regulated kinases that induce myocyte growth. RSK3 contains a unique N-terminal domain that mediates RSK3 binding to the muscle A-kinase anchoring protein (mAKAPβ) scaffold. We have previously published that disruption of RSK3-mAKAPβ complexes using a competing peptide inhibited the phenylephrine-induced hypertrophy of neonatal ventricular myocytes in vitro. In vivo, RSK3 gene deletion in mice attenuated the concentric cardiac hypertrophy induced by pressure overload. We hypothesize that RSK3 anchoring to mAKAPβ in myocytes is required for cardiac hypertrophy in vivo. METHODS AND RESULTS: Adeno-associated viruses (AAV) are gene therapy vectors in development for the treatment of human diseases owing to their nonpathogenic capability for transducing non-dividing cells and their long-term transgene expression. We have used a recombinant AAV2/9 vector to express a mAKAPβ RSK3-binding domain (RBD)-GFP fusion protein under the control of the cardiac myocyte-specific cardiac troponin T promoter. 3 day-old C57BL/6 mice were injected intraperitoneally with either AAV-RBD-GFP or AAV-GFP control virus. At 8 weeks of age mice were subjected to transverse aortic constriction to induce pressure overload (TAC) for two weeks. Cardiac hypertrophy was attenuated in mice injected with the AAV-RBD-GFP virus (biventricular weight indexed to tibial length (mg/mm): 7.7, 8.6, and 9.2 for AAV-RBD, AAV-GFP and non-injected TAC cohorts, respectively; p&lt;0.05 vs. both controls). Echocardiography both corroborated the inhibition of hypertrophy and revealed no deleterious effect on cardiac function attributable to the AAV-RBD-GFP vector. CONCLUSIONS: Anchored RSK3 regulates pathologic myocyte growth. AAV can successfully deliver a competing peptide inhibiting pathological hypertrophy and should be investigated further as a prevention and/or treatment for heart failure.
Plasma Glycolytic, Citric Acid Cycle, and Transaminase Enzyme Levels in Hamsters With a Transplanted Mammary Adenocarcinoma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M. West, M.D., M. Schwartz, M.D., H. J. Zimmerman, M.D.
Journal: JNCI Journal of the National Cancer Institute (1961)

Plasma levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LD), phosphohexose isomerase (PHI), aldolase (Aid), isocitric dehydrogenase (ICD), malic dehydrogenase (MD), and glutathione reductase (GR) were studied serially in hamsters for 30 days after transplantation of a non-metastasizing mammary adenocarcinoma. The transaminase (GOT and GPT) levels remained essentially normal throughout the studies. The highest levels of the other enzymes were observed between the 22d and the 30th days. Values for the PHI and ICD showed the greatest degree of elevation, levels of the Aid and MD somewhat less marked elevations, while values of the LD and GR were least elevated. The highest plasma-enzyme levels were found when tumor mass was greatest, but tissue necrosis was also prominent. Nevertheless, distinctly elevated levels appeared even when necrosis was negligible.
Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness
Authors: Shanru Li, Cynthia Koziol-White, Joseph Jude, Meiqi Jiang, Hengjiang Zhao, Gaoyuan Cao, Edwin Yoo, William Jester, Michael P. Morley, Su Zhou, Yi Wang, Min Min Lu, Reynold A. Panettieri, Edward E. Morrisey
Journal: Journal of Clinical Investigation (2016)

Asthma is one of the most common chronic diseases globally and can be divided into presenting with or without an immune response. Current therapies have little effect on nonimmune disease, and the mechanisms that drive this type of asthma are poorly understood. Here, we have shown that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness (AHR) without eosinophilic inflammation. Transcriptome analysis revealed that loss of Foxp1 and Foxp4 expression induces ectopic expression of neuropeptide Y (Npy), which has been reported to be present in the airways of asthma patients, but whose importance in disease pathogenesis remains unclear. Treatment of human lung airway explants with recombinant NPY increased airway contractility. Conversely, loss of Npy in Foxp1- and Foxp4-mutant airway epithelium rescued the AHR phenotype. We determined that NPY promotes AHR through the induction of Rho kinase activity and phosphorylation of myosin light chain, which induces airway smooth muscle contraction. Together, these studies highlight the importance of paracrine signals from the airway epithelium to the underlying smooth muscle to induce AHR and suggest that therapies targeting epithelial induction of this phenotype may prove useful in treatment of noneosinophilic asthma.
Will primary care trusts lead to US-style health care? : The NHS is probably safe in the government's hands
Authors: John Appleby
Journal: BMJ (2001)

Editor—Pollock has presented a one sided view and explanation of some of the policy actions she suggests may drive the NHS towards a US-style health care system.1 Her view is that, as a result of a combination of historic and current policy changes, NHS trusts will be burdened with such large debts that they will be forced to embark on several actions that will raise “the spectre of US-style health maintenance organisations.”

But her initial premise (of rising cost pressures) is a bit wobbly.

Firstly, although capital charges do indeed represent a cost to trusts in the NHS, these are not new. Introduced as part of the internal market, they were matched on the purchasing side so that the net sum across the NHS was zero.

Over time, the direct link between an individual trust's charge and the compensating money given to its purchasers has been broken. Providers have had to think more carefully about their use of capital. Overall, this is a good thing as capital, like labour, is not a free good in the NHS: its cost can be measured in the forgone benefits of using resources in some alternative way.

Secondly, the repayments that trusts have to make on any private finance initiative or public-private partnership deal are, again, as Pollock points out, also a cost, but one that is also recovered from purchasers. Just as publicly funded capital schemes are paid for from the Exchequer, so private finance initiative schemes are ultimately paid for by the Exchequer (out of taxation), but the route is different (via purchasers' allocations rather than a direct (repayable) grant from the Exchequer).2

Thirdly, although the repayments overall will escalate over the coming years, this is simply because the government is keen to see more deals struck under the initiative.

Having apparently established that trusts will be facing a mounting bill for capital, Pollock then states that unless more money is injected into the NHS to help meet these costs, patient and clinical services will be under threat, or other unpleasant actions will have to be taken that will destroy the NHS as we know it.

But, of course, more money has been allocated to the NHS. And part of this pays for private finance initiative costs and will flow from purchasers to providers with private finance initiative and public-private partnership deals, and on to private consortiums (which paid for and built NHS facilities). If these schemes had been funded via the conventional public route then some of the settlement would have been used in this way instead. Either way, it could be interpreted (as Pollock has done) as threatening patient services (although I would have thought that hospitals and other facilities are generally seen by most people as an integral part of patient services).

There are legitimate arguments against the private finance initiative and public-private partnership, but in this paper Pollock fails to articulate them.
Evaluation of KIR4.1 as an Immune Target in Multiple Sclerosis
Authors: Anne Chastre, David A Hafler, Kevin C O'Connor
Journal: New England Journal of Medicine (2016)

An enzyme-linked immunosorbent assay of antibodies in the serum of 86 patients with multiple sclerosis and that of 51 healthy controls that used KIR4.1 as the target protein showed no significant between-group difference.
Subarachnoid Hemorrhage from Intracranial Aneurysms
Authors: Thoralf M. Sundt, Jack P. Whisnant
Journal: New England Journal of Medicine (1978)

We analyzed the management of 310 patients with acute subarachnoid hemorrhage from a ruptured intracranial aneurysm, 280 of whom survived to operation, according to preoperative neurologic function, location and size of the aneurysm and timing of operation. Severe initial bleeding, rebleeding (usually within two weeks) and delayed ischemia were major preoperative problems; 10 per cent died, and 13 per cent deteriorated before operation. Operative mortality was 5 per cent, ranging from 1.6 per cent of patients with normal preoperative neurologic function to 35 per cent of severely disabled patients. Intraoperative complications (5 per cent of cases) related chiefly to the size and location of the aneurysm, but postoperative delayed ischemia (minor and reversible in 10 per cent and severe in 5 per cent) related to timing of operation and occurred primarily in patients afflicted within the previous 10 days. The results of surgical treatment, including preoperative deaths, were better than the natural history of the illness, the difference being apparent after one month's observation. (N Engl J Med 299:116–122, 1978)
A Randomized Trial of Intravenous Tissue Plasminogen Activator for Acute Myocardial Infarction with Subsequent Randomization to Elective Coronary Angioplasty
Authors: A D Guerci, G Gerstenblith, J A Brinker, N C Chandra, S O Gottlieb, R D Bahr, J L Weiss, E P Shapiro, J T Flaherty, D E Bush
Journal: New England Journal of Medicine (1987)

Original Article from The New England Journal of Medicine — A Randomized Trial of Intravenous Tissue Plasminogen Activator for Acute Myocardial Infarction with Subsequent Randomization to Elective Coronary Angioplasty
Cavernous Angioma of the Brain Stem Mimicking Multiple Sclerosis
Authors: Magnus Vrethem, Karl-Åke Thuomas, Jan Hillman
Journal: New England Journal of Medicine (1997)

To the Editor: Vascular malformations of the brain stem are relatively uncommon and represent about 7 percent of all vascular malformations of the brain.1 They may be manifested as subarachnoid or intraparenchymatous hemorrhages, seizures, or fluctuating or slowly progressive neurologic deficit. In 50 percent of cases, vascular malformations of the brain stem are not visible with angiography.1 Also, standard computed tomography (CT) of the brain may fail to detect small vascular malformations of the brain stem, whereas magnetic resonance imaging (MRI) offers better sensitivity. There are case reports of vascular malformations simulating multiple sclerosis that are revealed after many years . . .
Moving from 2D to 3D conformal radiotherapy (3DCRT) in locally advanced head and neck cancer: A dosimetric comparison
Authors: S. G. Billan, V. Bakouche, A. Nevelsky, R. Abdah-Bortnyak, R. Uziel, F. Rawashdeh, E. Gez, R. Epelbaum, A. Kuten
Journal: Journal of Clinical Oncology (2007)

16530 Background: The aim of this study is to evaluate the dosimetric parameters of 3D CRT in head and neck tumors, to compare with hypothetical 2D plans, and to evaluate the acute toxicity. Methods: A total of 33 patients with median age of 62 years (range: 23–87 ) and with histologically proven head and neck cancer were consecutively treated with 3D CRT using a 6-field photon beam technique. 9 patients had supraglottic carcinoma, 5 - glottic carcinoma, 4- nasopharyngeal carcinoma, 4 - thyroid carcinoma, 2- oropharyngeal cancer, 3 - carcinoma of oral cavity, 1- carcinoma of hypopharynx, 1- maxillary sinus carcinoma, 3- unknown primary, 1- recurrent laryngeal carcinoma. 28 patients received concomitant chemotherapy and 13 were treated with neoadjuvant chemotherapy, 5 patients received postoperative radiotherapy and 28 received definitive radiotherapy. A comparative analysis of dose distributions and dose-volume histograms (DVH) between 2D and 3D plans for 11 patients with glottic and supraglottic carcinoma for the initial 50 Gy (since the 20 Gy boost was given almost identical in both technique) was carried out. Toxicity analysis was determined according to RTOG/EORTC toxicity criteria. Results: The mean dose coverage V45 (%) of the primary planning target volume for 2D and 3D plans was 89.6% and 94.8%, respectively (p=0.005). The mean volumes of the hot spots ( 110% of prescribed dose) for primary target volumes for 2D and 3D plans were: 61cc (range: 8.7–130.2 cc) and 26.2 cc (range: 0–49.8 cc), respectively (p=0.005). The mean dose to the parotid glands was significantly lower with 3D CRT (22.1 Gy and 24.7 Gy) compared to 2D technique (45.2 Gy and 46.4 Gy) for right and left parotids, respectively (p=0.003). The maximal spinal cord dose was: mean 45.3 Gy and 41.6 Gy for 2D and 3D CRT, respectively (p=0.003). Gr3 acute toxicity was observed in 3 patients (9%) , and Gr 4 toxicity in 6 patients ( 18%). Treatment was interrupted in 3 patients only. Conclusions: 3DCRT in head and neck cancer permits good coverage of the PTV .The low rate of acute toxicity can be explained by improving the dosimetric parameters of organs of risk and reducing the volume of hot spots in the target. Using 3D CRT for laryngeal carcinoma allows parotid sparing with a mean parotic dose of less than 26 Gy No significant financial relationships to disclose.
Cytologic Appearance of Cells Dissociated From Rat Colon and Their Separation by Isokinetic and Isopyknic Sedimentation in Gradients of Ficoll&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T P Pretlow, A J Stinson, T G Pretlow, G L Glover
Journal: JNCI Journal of the National Cancer Institute (1978)

Several methods for obtaining colon epithelial cells in suspension were compared. The largest number of epithelial cells per gram of colon was obtained in suspension when the colon was dissociated with 0.1% Pronase. Fivefold more cells per gram of tissue were obtained from the proximal 5 cm of colon than from the terminal 5 cm of colon. Several well-defined types of cells were observed in low frequency. They have not been described previously in normal colon. Suspensions of cells from colons of F344 rats always contained copious mucoid gel that was partially eliminated by washing the cells three times in culture medium with 10% fetal calf serum. Velocity sedimentation in a previously described isokinetic gradient of Ficoll in tissue culture medium permitted the separation of epithelial cells from lymphocytes and red blood cells. Type 2 cells, believed to be a subpopulation of epithelial cells, were obtained in a maximum purity of 95.7 +/- 1.2%. The frequency of 8 other cell types and their purification, when possible, are presented. Epithelial cells were separated from most bacteria and could be cultured with antibiotics after separation in the density gradient.
P186 Chest Drain Care Bundle improves Chest Drain Insertion in District General Hospital
Authors: H Steer, J Hutton, S Graham, R Jones
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Chest drain insertion is a common advanced procedure with a significant associated risk of pain, distress and serious complications. Nationally, audit and patient safety work has highlighted a number of safety concerns around chest drain insertion. Previous audit work has demonstrated poor levels of documentation; particularly around use of pre-medication, use of ultrasound guidance and consent. This has obvious potential consequences for patient safety and thus is an important target for improvement work. <h3>Method</h3> National best practice standards were identified through review of national guidance. This work quantifies current standards of documentation in Gloucestershire against national best practice standards. Drain insertion was prospectively analysed over a 3 month period to establish baseline standards of documentation. A combination of accessible and easy-to-read guidelines, education and the introduction of a chest drain bundle were introduced. Chest drain insertion was then re-audited over a further 3 month period and assessed for improvement. <h3>Results</h3> The data set included 24 pre-intervention and 23 post-intervention. Results demonstrated an improvement in many areas of documentation. Prior to the intervention, documentation was found to be poor; especially in areas related to consent, use of ultrasonography, pre-medication, post-procedure advice, details regarding length and size of drain and investigations requested. Overall the results showed improvement in most areas of documentation. The care bundle demonstrated improvement in documentation compared to the classical “freehand” documentation. However, only 40% of cases used the new proforma due to a mixture of staff rotation and an unexpectedly high proportion of drains inserted in non-targeted areas including the emergency department, theatre and intensive care. Outcomes were also compared against the recent national findings from the 2015 British Thoracic Society Pleural Procedures audit. Use of the chest drain bundle created improved compliance with several key standards; particularly written consent, bedside ultrasonography, nursing chest drain observation and care on designated respiratory ward. <h3>Conclusion</h3> The chest drain care bundle improves documentation of this important procedure. This is important to ensure uniformity in clinical “best” practice, aid communication and protect patients. Further improvements can be made by more widespread education and access to the care bundle.