tbuckley/cabot-search huggingface dataset:
P26 Measuring the value of a consultant-led Community Respiratory (CORE) Multidisciplinary Team (MDT) in a deprived inner city area: Achieving parity in respiratory care for housebound sick patients: Abstract P26 Table 1
Authors: M Heightman, D Dullaghan, A Rafferty, E Jones, H Townes, L Gardiner, J Dzingai, C Nimoh-Bing, H Broomfield, G Fabris, R Dharmagunawardena, L Restrick, M Stern
Journal: Thorax (2015)

<h3>Introduction</h3> The shift of chronic respiratory disease management to the community has stimulated development of multidisciplinary community respiratory services (CORE-MDT). Measuring the value of these services is challenging but is important for quality improvement and commissioning. This retrospective analysis of the activity of an inner city community respiratory service documents the nature of the caseload, interventions made and their impact on usual care provision. <h3>Method</h3> The CORE-MDT, accepting referrals from GPs and three acute hospital trusts, is based at three localities and includes respiratory nurses, physiotherapists, quit-smoking advisors, clinical psychologists and respiratory consultant support. Care is delivered at home with hospital in-reach during every admission. A bespoke iPad App database (HandBase) was designed for information documentation and sharing from case management and consultant-led MDT discussion of patients. A retrospective analysis of records was made of sequential referrals from Sept 2014 to March 2015. Demographics, disease severity, comorbidities, social deprivation, duration of management, nature of intervention and healthcare resource utilisation over 6/12 were documented. Hospital data allowed estimation of bed-day savings based on average length of stay for acute exacerbations of COPD (AECOPD). <h3>Results</h3> Records from 83 patients (most with COPD) were reviewed. Mean [SD] FEV1: 0.98 [0.38]L. Patients had multiple comorbidities, high smoking prevalence, deprivation and isolation (Table 1). Mean[SD] duration of CORE team management: 5.2[4.9]months. ~50% of patients were then discharged to usual care. 17/34 (50%) completed pulmonary rehabilitation, 11 saw a psychologist and 6/12 (50%) achieved smoking cessation. Mortality was 6%. Hospital bed-days usage (p = 0.001) and GP visits (p = 0.02) were reduced during active case management compared to the year before referral. Domiciliary management of 105 AECOPD reduced GP workload with an estimated £58 000 savings in admission avoidance for (n = 30) patients with baseline hypoxia &lt;92% or &gt;2 admissions in the year prior to CORE management HRG DZ-21K: £2000/admission). <h3>Conclusions</h3> The service has improved quality of care for these complex sick patients and generated significant savings in GP workload and admission avoidance which should underpin service commissioning and provision. The use of Handbase has facilitated consistency in evidence-based care and record-keeping, information sharing and evaluation of CORE-MDT activity.
Is there a preferred dose of palonosetron? Results of an abstracted data (AD) meta-analysis (MA) of all eight randomized double-blind (RDB) studies and the impact on guideline considerations
Authors: H. Raftopoulos, E. Bria, R. Gralla, M. Lesser, B. Napolitano, D. Giannarelli
Journal: Journal of Clinical Oncology (2009)

9636 Background: Controversy continues whether there should be a guideline-preferred 5-HT3 antagonist. Large trials with palonosetron (palo) 0.25 mg demonstrated advantages over earlier 5-HT3 agents in preventing emesis with chemotherapy (chemo). Guideline groups have not consistently adopted palo as the preferred 5HT3 agent since these trials omitted the recommended addition of dexamethasone (dex). A recent 1100 patient RDB trial (Yoshizawa, ESMO 2008) found superiority for palo 0.75 mg + dex versus granisetron 3 mg + dex. Both palo and granisetron are approved at varying doses in different countries. This abstracted-data MA was conducted to see if this palo dosing yields differences. If not, results from randomized trials at either dose can aid practice and guideline committees in 5-HT3 agent selection. Methods: A literature search and colleague inquiry identified RDB trials that included treatment arms with 0.25 mg and 0.75 mg of palo. MA primary endpoint: Complete Response (CR - no vomiting, no rescue) over days 1–5 after chemo. Secondary endpoints: 1)Acute CR (day 1), 2)Delayed CR (days 2 - 5), 3) Grade 3–4 toxicities. Data were abstracted and checked by at least 2 reviewers. CMA software v2 (Biostat, NJ) was used to calculate relative risk ratios (palo 0.75 vs palo 0.25) with 95% confidence intervals (CI). Results: 8 trials with 1926 patients included all RDB studies with these palo doses - 4 with HEC and 4 with MEC (6 with IV and 2 with oral palo). The Cochrane Q test indicated no heterogeneity (het) for overall and delayed CR; het seen in the acute setting was accounted for by the 2 smaller dose-finding studies. No significant toxicity differences were found. Conclusions: Palo doses of 0.25 mg or 0.75 mg yield very similar efficacy and safety with both HEC and MEC in this literature-based MA. Results with either dose can aid in practice and guideline considerations for all chemo groups studied. [Table: see text] [Table: see text]
Aspirin Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway
Authors: Tao Liu, Yoshihide Kanaoka, Nora A. Barrett, Chunli Feng, Denise Garofalo, Juying Lai, Kathleen M. Buchheit, Neil Bhattacharyya, Tanya M. Laidlaw, Howard Katz, Joshua A. Boyce
Journal: Journal of Allergy and Clinical Immunology (2016)
Evidence for Liver Disease Preceding Amino Acid Abnormalities in Hereditary Tyrosinemia
Authors: Margaret K. Hostetter, Harvey L. Levy, Harland S. Winter, George J. Knight, James E. Haddow
Journal: New England Journal of Medicine (1983)

In hereditary tyrosinemia, an autosomal recessive disorder of infants, it has been postulated that hepatic toxicity arising from defective degradation of tyrosine accounts for the severe liver disease that is a feature of this condition. We measured the concentration of alpha-fetoprotein, a marker for liver disease, and of amino acid in cord blood from three infants with hereditary tyrosinemia and found that the concentration of alpha-fetoprotein was greatly increased at birth, whereas the level of tyrosine was normal or not specifically elevated, and that hypertyrosinemia developed only postnatally. These results indicate that liver disease is prenatal in hereditary tyrosinemia and that therapy aimed at reduction of the elevated tyrosine level is unlikely to be of fundamental value. (N Engl J Med 1983; 308:1265–7.)
Use of Live-Measles-Virus Vaccine to Abort an Expected Outbreak of Measles within a Closed Population
Authors: Sumner Berkovich, Saul Starr
Journal: New England Journal of Medicine (1963)

THE use of live-measles-virus vaccine to modify an expected outbreak of regular measles among institutionalized children would have certain advantages over gamma globulin given for the same purpose. Whereas commercial globulin preparations contain variable quantities of measles antibody that at best offer transient immunity, the vaccine almost always infects the seronegative vaccinee and causes a mild illness followed by immunity of undetermined but possibly lifelong duration.1 The introduction of regular measles into an isolated ward of tuberculous children allowed us to test under carefully controlled conditions the modifying capacity of live vaccine and gamma globulin in combination. The expected outbreak . . .
Abstract 2605: The geranylgeranyltransferase I inhibitor GGTI-2418 suppresses multiple myeloma malignancy in the 5TMG1 mouse model
Authors: Hua Yang, Michael F. Emmons, Christopher Cubitt, Ken Shain, Domenico Coppola, Daniel Sullivan, Conor C. Lynch, Lori Hazlehurst, Said M. Sebti
Journal: Cancer Research (2015)

Abstract Little is known about the contributions of geranylgeranylated proteins to multiple myeloma (MM) malignancy, and whether targeting geranylgeranyltransferase I (GGT-1) is a viable therapeutic approach in myeloma is yet to be explored. In this study, we investigated the effects of GGTI-2418, a GGT-1 inhibitor that has reached phase I clinical trials, on MM malignancy in the 5TMG1 mouse model, where GGTI-2418 effects were assessed in the confines of the bone microenvironment that recapitulates the clinical disease in humans. GGTI-2418 treatment significantly decreased the serum levels of the MM biomarker IgG2B (M-protein) as well as the percentage of MM tumors within the tibia as demonstrated by H&amp;E staining. X-ray and micro-CT analyses also identified that GGTI-2418 prevented MM induced bone disease with significantly lower tumor induced osteolysis and trabecular bone volume loss noted. Furthermore, treatment of mice with GGTI-2418 resulted in a significant activation of caspase 3 (apoptosis induction), accumulation of nuclear p27Kip in MM tumors (a positive prognostic biomarker for MM patients), and reduction of α-SMA levels in myofibroblasts surrounding the sinusoidal vasculature, suggesting decreased vascularization of marrow blood vessels. Importantly, GGTI-2418 treatment resulted in a significant increase in mouse median survival and delay in the onset of limb paralysis. In cell culture studies, GGTI-2417, the methylester pro-drug of GGTI-2418 that is better taken up by cultured cells, inhibited MM proliferation, increased p27kip levels, induced apoptosis and sensitized MM cells to bortezomib. Taken together, our preclinical studies suggest targeting GGT-1 as a viable therapeutic approach in MM, and warrant the investigation of GGTI-2418 in the clinic. Citation Format: Hua Yang, Michael F. Emmons, Christopher Cubitt, Ken Shain, Domenico Coppola, Daniel Sullivan, Conor C. Lynch, Lori Hazlehurst, Said M. Sebti. The geranylgeranyltransferase I inhibitor GGTI-2418 suppresses multiple myeloma malignancy in the 5TMG1 mouse model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2605. doi:10.1158/1538-7445.AM2015-2605
Clonal Proliferations of Cells Infected with Epstein–Barr Virus in Preinvasive Lesions Related to Nasopharyngeal Carcinoma
Authors: Rajadurai Pathmanathan, Umapati Prasad, Robert Sadler, Kathryn Flynn, Nancy Raab-Traub
Journal: New England Journal of Medicine (1995)

The Epstein–Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.
Common Reasons That Asymptomatic Patients Who Are 65 Years and Older Receive Carotid Imaging
Authors: Salomeh Keyhani, Eric M. Cheng, Ayman Naseri, Ethan A. Halm, Linda S. Williams, Jason Johanning, Erin Madden, Soraya Rofagha, Alexandra Woodbridge, Ann Abraham, Rosa Ahn, Susan Saba, Elnaz Eilkhani, Paul Hebert, Dawn M. Bravata
Journal: JAMA Internal Medicine (2016)

National guidelines do not agree on the role of carotid screening in asymptomatic patients (ie, patients who have not had a stroke or transient ischemic attack). Recently, several physician organizations participating in the Choosing Wisely campaign have identified carotid imaging in selected asymptomatic populations as being of low value. However, the majority of patients who are evaluated for carotid stenosis and subsequently revascularized are asymptomatic.
Metastatic Renal Cell Carcinoma in the Thyroid Gland and Pancreas Showing Uptake on 68Ga DOTATATE PET/CT Scan
Authors: Gowri L. Kanthan, Geoffrey Paul Schembri, Jaswinder Samra, Paul Roach, Edward Hsiao
Journal: Clinical Nuclear Medicine (2016)

68Ga DOTATATE PET/CT is an imaging technique used in the diagnosis of neuroendocrine tumors. We report a case of 66-year-old woman with a history of surgically removed renal cell carcinoma who presented for a DOTATATE PET/CT scan to characterize a newly diagnosed pancreatic lesion. DOTATATE-avid lesions were identified in the thyroid gland and pancreas. Subsequent biopsy confirmed the diagnosis of metastatic renal cell carcinoma at both sites. It is important to be aware that tumors other than neuroendocrine tumors may also show uptake on DOTATATE PET/CT scan. A biopsy may be required if lesions are identified at atypical sites.
Adjuvant weekly docetaxel (D) for high-risk prostate cancer patients (pts) after radical prostatectomy (RP): Preliminary data of a multicenter pilot trial
Authors: E. Rosenbaum, A. Kibel, B. J. Roth, G. Wilding, R. Dreicer, G. Chatta, D. Petrylak, R. S. Dipaola, T. M. Beer, M. A. Eisenberger
Journal: Journal of Clinical Oncology (2004)

4649 Background: Over the past decade more PC pts are diagnosed early and treated locally. 40–60% recur after local treatment. We conducted a pilot post RP adjuvant study in pts at high risk for recurrence after RP. Study objectives were to evaluate: 1. toxicity (tox) 2. feasibility of 6 months of adjuvant D treatment and 3. Incidence of PSA relapses (>0.2ng/ml) in 2 and 3 years (vs. matched controls). Methods: Pts with confirmed PC, within 3 months of RP, and without distant metastases, organ dysfunction, RT, or systemic treatment were eligible. Pathology was centrally reviewed (JHU) and risk assessment was based on a multivariate Cox proportional hazards model (Rw' = lymph node (0/1)*1.43 + seminal vesicle (0/1)*0.51 + surgical margin (0/1)*1.15 + modified Gleason score (MGS) (0–4) * 0.71) [MGS: Gleason 5=0; 3+3=1; 3+4=2; 4+3=3; 8–10=4]. The minimum value for study entry was based on a projected 50% rate of recurrence by 3 years = Rw' > 2.84. (Roberts, et al. Urology, 2001). Treatment included I.V.D 35mg/m2 Days 1, 8, 15 of a 28-day cycle x 6 cycles starting 4–12 weeks after surgery. We have 90% power to detect a 3-year progression free survival rate of 69% versus the control rate of 50%, α=0.05. Results: 77 pts were registered (2/02–12/03). Median age: 60 (43–76). Median Rw' 4.07 (2.85–5.93). Tox in the first 51 pts. Grade IV: hyperglycemia 3.9%. Grade III: hyperglycemia 9.8%, dyspnea 5.8%, leukopenia 3.9%. 1 pt. required dose reduction (LFT's), only 2 had delay in Rx. One death unrelated to D. Grade I/II (>30%): fatigue, alopecia, nail changes, diarrhea, dyspepsia, dyspnea, flushing, hyperglycemia, insomnia, nausea and peripheral sensory neuropathy. Data on PSA progression is preliminary at this time. Conclusions: Post-operative adjuvant weekly D for high risk PC pts is feasible and has moderate reversible toxicity. Rapid accrual suggests high-level of pt and physicians interest. Additional follow up is needed for outcome assessment. (Supported by Aventis). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Aventis; Celegene AstraZeneca; Aventis; Berlex; Millenium
VEGFB/VEGFR1-Induced Expansion of Adipose Vasculature Counteracts Obesity and Related Metabolic Complications
Authors: Marius R. Robciuc, Riikka Kivelä, Ian M. Williams, Jan Freark de Boer, Theo H. van Dijk, Harri Elamaa, Feven Tigistu-Sahle, Dmitry Molotkov, Veli-Matti Leppänen, Reijo Käkelä, Lauri Eklund, David H. Wasserman, Albert K. Groen, Kari Alitalo
Journal: Cell Metabolism (2016)
A Mutation in the Vasopressin V2-Receptor Gene in a Kindred with X-Linked Nephrogenic Diabetes Insipidus
Authors: John J. Merendino, Allen M. Spiegel, John D. Crawford, Anne-Marie O'Carroll, Michael J. Brownstein, Stephen J. Lolait
Journal: New England Journal of Medicine (1993)

Hereditary nephrogenic diabetes insipidus is a rare, X-linked disorder manifested by an inability to concentrate the urine despite high plasma concentrations of arginine vasopressin or the administration of large doses of vasopressin or its analogues1,2. Affected males have profound hyposmotic polyuria soon after birth, often leading to recurrent episodes of severe dehydration. Unless recognized and treated early, these episodes may lead to failure to thrive, growth retardation, repeated bouts of cerebral edema with resultant mental retardation, or death. Females who are carriers of the gene for the disease have symptoms that range from a defective urinary-concentrating ability demonstrable . . .
DNA vaccine encoding a prostate-specific protein elicits CD8 T cell immunity and tissue-specific inflammation
Authors: Laura E. Johnson, Douglas G. McNeel
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1244 

Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and a prostate-specific protein shared by rats and humans. Previous studies in Copenhagen rats have indicated that rats immunized with vaccinia expressing human PAP developed a cross-reactive cytotoxic T cell response (CTL) activity to rat PAP that results in prostate inflammation. However, a problem with some viral-based immunizations has been that immune responses elicited to the viral vector limit the possibility of multiple immunizations. We hypothesized that DNA vaccines would provide an efficient immunization method to elicit an antigen-specific CD8 T cell immune response without a secondary immune response to the viral carrier. In order to test this hypothesis, Lewis rats were immunized twice with either a DNA-based (pTVG-HP) or vaccinia-based (VV-HP) vaccine each encoding human PAP. We determined that rats immunized with a DNA vaccine encoding PAP resulted in PAP-specific antibodies, antigen-specific CD4 and CD8 T cells, IFNγ production, and CTL activity. Some animals developed a cross-reactive response that led to prostate tissue inflammation and destruction. Rats immunized with VV-HP did not develop proliferating PAP-specific T cells but had a strong vaccinia-specific CD4 and CD8 T cell immune response. Thus, the immune response elicited by means of a DNA vaccine was qualitatively similar to that elicited by means of a viral vaccine, but the DNA vaccine permitted multiple immunizations that resulted in the generation of a PAP-specific immune response. Overall, DNA vaccines provide a safe and effective method of generating prostate antigen-specific T cell responses. These findings support the investigation of PAP-specific DNA vaccines in human clinical trials.
P192 Clinical effectiveness of non-invasive ventilation in patients with Motor Neuron Disease
Authors: D Freeman, A Jothieswaran, M Mascareno, N Chaudhry, S Bokhari, TW Felton, AM Bentley
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> The use of long term non-invasive ventilation (NIV) for type II respiratory failure caused by Motor Neuron Disease (MND) is well recognised. In patients with MND and good bulbar function, NIV has been shown to improve survival and quality of life.<sup>1</sup> NIV use in patients with MND has increased since the publication of the National institute of Clinical Health Excellence guidelines in July 2010. Our objective was to identify the clinical effectiveness of NIV in all patients with MND referred to a large tertiary referral teaching hospital service. <h3>Methods</h3> All patients with MND established on NIV were identified retrospectively from a clinical database. Patients were excluded from the analysis if there was another diagnosis as the main indication for establishing NIV. All patient data was anonymised. A Kaplan-Meier survival analysis was performed and the median survival was estimated. <h3>Results</h3> 222 patients with MND established on NIV were identified. The median age was 64 years (range 19–90 years). One hundred and forty patients (63%) were male and 82 (37%) female. The median survival was 436 days on NIV. The Kaplan-Meier survival curve is shown below. <h3>Conclusion</h3> A median survival of 436 days compares favourably with the median survival of 219 days identified in patients with MND receiving NIV in the trial by Bourke <i>et al</i>. Our patient cohort included patients with both limb onset and bulbar onset forms of the disease. The impact on survival may, in part, be due to NIV but overall improvements in medical care, supporting adequate nutrition and assisted cough techniques in a specialist centre will have contributed. <h3>Reference</h3> 1 Bourke SC, <i>et al</i>. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. <i>Lancet Neurol</i>. 2006;<b>5</b>:140–7
Some Re-Evaluations of the<i>Build and Blood Pressure Study, 1959</i>as Related to Ponderal Index, Somatotype and Mortality
Authors: Carl C. Seltzer
Journal: New England Journal of Medicine (1966)

FOR more than fifty years a number of life-insurance companies have been carrying out studies pertaining to the heights, weights and mortality experience of their policy-holders.1 , 3 The most recent of these3 represents a detailed evaluation of variations in height and weight, as well as blood pressure, in relation to disease, mortality ratio and cause of death. Although there are some differences in detail the results of these studies are in accord in indicating a consistent gradient advance in mortality with increasing degrees of o-6 rweight.4 5 6 The collective impression created is that virtually all degrees of overweight constitute risks to . . .
Inhibition of Glucose Transport into Rat Islet Cells by Immunoglobulins from Patients with New-Onset Insulin-Dependent Diabetes Mellitus
Authors: John H. Johnson, Billy P. Crider, Kay McCorkle, Marilyn Alford, Roger H. Unger
Journal: New England Journal of Medicine (1990)

Because glucose-stimulated insulin secretion is selectively impaired during the development of insulin-dependent diabetes mellitus (IDDM), we tested the possibility that the glucose transporter of pancreatic islet beta cells is a target of the autoimmune process in patients with IDDM.
Hypophosphatemic Osteomalacia Associated with Nonendocrine Tumors
Authors: Robert M. Salassa, Jenifer Jowsey, Claude D. Arnaud
Journal: New England Journal of Medicine (1970)

Two adult men with severe adult-onset hypophosphatemic osteomalacia made spectacular recoveries after removal of small benign sclerosing hemangiomas. In both cases removal of the tumor was followed by an increase in the serum inorganic phosphate to high-normal levels, relief of clinical symptoms and roentgenographic evidence of healing of the osteomalacia. In the second case, removal of the tumor increased serum immunoreactive parathyroid hormone. Some cases of adult-onset hypophosphatemic osteomalacia apparently are directly related to the presence of nonendocrine tumors that elaborate a humoral substance (other than parathyroid hormone) that markedly increases the renal clearance of phosphate, resulting in hypophosphatemia and failure of skeletal mineralization.
Elevated Histaminase (Diamine Oxidase) Activity in Small-Cell Carcinoma of the Lung
Authors: Stephen B. Baylin, Martin D. Abeloff, Kathleen C. Wieman, J. Walton Tomford, David S. Ettinger
Journal: New England Journal of Medicine (1975)

To investigate the possible embryologic relation between small-cell carcinoma of the lung and medullary thyroid carcinoma, we measured plasma histaminase (an enzyme found in medullary carcinoma tissue) in 25 patients with small-cell tumors. The assays used histamine and putrescine as substrates. Thirty-two per cent of the patients by the histamine assay, and 31 per cent by the putrescine, had values greater than +2 S.D. from the mean for 63 normal persons. In contrast, among 20 patients with squamous and large-cell lung tumors, one (by the histamine assay), and two (by the putrescine) had elevated values. In four of five autopsy cases, histaminase was high in small-cell carcinoma tissue. The enzyme in plasma and in tumor behaved as classic histaminase in substrate specificity, and in response to inhibitors. The data support the proposed embryologic relation between small-cell lung carcinoma and medullary thyroid carcinoma, and further associate histaminase with some neural crest tumors.