tbuckley/cabot-search huggingface dataset:
Generic Prescribing of Antidepressants
Authors: P Bruck, C A Antao, J A Henry
Journal: Journal of the Royal Society of Medicine (1992)

Analysis of National Health Service prescription data for the antidepressants from 1980 to 1989 shows a consistent secular trend towards the increased use of generic names on prescriptions for this group of drugs. This apparently reflects national trends for all drugs, and was similar for most antidepressants. However, generic prescribing had by 1989 increased significantly more rapidly with fluvoxamine, which was introduced in 1987. The two drugs introduced in 1989, fluoxetine and amoxapine, also had a high generic prescribing rate in their year of introduction. Increased generic prescribing may become a feature with further new drugs. However, the use of the generic name on the prescription has relatively little influence on what is dispensed to the patient. Pharmacists may dispense a brand name when given a generic prescription. Moreover, pressures on doctors to write generic names on prescriptions may have limited relevance for some drugs; generic alternatives were available for only four out of 22 antidepressants.
Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study.
Authors: G Gasparini, O Caffo, S Barni, L Frontini, A Testolin, R B Guglielmi, G Ambrosini
Journal: Journal of Clinical Oncology (1994)

To evaluate the efficacy and toxicity of single-agent vinorelbine (VNB), a semisynthetic vinca alkaloid, in patients with breast cancer previously treated with other chemotherapeutic regimens for metastatic disease.Sixty-seven of 70 patients with assessable disease entered onto the study were assessable. The main characteristics were as follows: median age, 60 years (range, 41 to 77); median performance status (PS; Karnofsky score), 90 (range, 60 to 100); and number of previous chemotherapeutic regimens given--one in 17, two in 27, three in eight, four in two, and five in one patient. The dominant sites of metastasis were viscera in 40, bone in 16, and soft tissues in 11 patients. VNB was administered beginning with the dose of 20 mg/m2 by 60-minute intravenous (iv) infusion weekly, with a dose escalation up to 25 mg/m2 if the first four courses were well tolerated. The treatment was continued until disease progression.Overall, 845 courses of VNB were given (median, 10; range, eight to 33). Objective responses were as follows: complete response (CR) in three (4.5%), partial response (PR) in 21 (31.2%), stable disease (SD) in 20 (30%), and progressive disease (PD) in 23 patients (34.3%). Twenty-four of 67 assessable patients obtained a major objective response (CR or PR, 36%; 95% confidence interval [Cl], 24% to 47%). Thirty-three percent of patients had a > or = 33% reduction of dose-intensity (DI). The median time to progression was 18 weeks. The drug was active in patients pretreated with either cyclophosphamide, methotrexate, and fluorouracil (CMF) or anthracyclines. The most relevant toxicity observed was myelosuppression: 17 (25%) and 19 patients (28%) had World Health Organization grade III, and six (9%) and six patients (9%) had grade IV leukopenia and granulocytopenia, respectively; two (3%) and two patients (3%) had grade III and IV anemia, respectively. Nonhematologic toxicities were phlebitis (grade II or III in 15 patients), alopecia (grade I or II in 16), nausea and vomiting (grade II or III in 15), diarrhea (grade II in two), constipation (grade II or III in 16), stomatitis (grade II or III in 13), peripheral neuropathy (grade II in seven), and asthenia (grade II in five).This study shows that VNB is an effective and well-tolerated agent in pretreated patients with advanced breast cancer. This drug does not seem to present cross-resistance with previous CMF or anthracycline regimens. Future clinical trials should be designed to prove whether the inclusion of VNB in combination chemotherapy regimens, or whether an enhancement of its dose-intensity using bone marrow growth factors, is able to improve further the efficacy of this drug in breast carcinoma.
Abstract 4097: Vacuolar ATPase subunit a2 is associated with immunosuppression in cancer
Authors: Gajendra K. Katara, Arpita Kulshrestha, Mukesh Jaiswal, Alice Gilman-Sachs, Kenneth D. Beaman
Journal: Cancer Research (2014)

Abstract Macrophage polarization contributes to distinct human pathologies. In tumors, a polarized M2 phenotype called tumor-associated macrophages (TAMs), are associated with promotion of invasion and angiogenesis. In cancer cells, vacuolar ATPase (V-ATPase), a multi-subunit enzyme, is expressed on the plasma/vesicular membranes and critically influences the metastatic behavior. In addition, the soluble, cleaved N-terminal domain of a2 isoform of V-ATPase (a2NTD) is associated with in vitro induction of pro-tumorigenic properties in monocytes. Monocytes induced with recombinant a2NTD showed polarization towards M2 macrophage subtype by expressing high levels of mannose receptor-1, Arginase-1, IL-10, MMP-9, VEGF and TGF-β. Additionally, co-culture of these macrophages enhances invasion and angiogenesis of tumor cells and suppression of T cell activation. This activity of the a2 isoform of V-ATPase (a2V) caused us to further investigate its role in cancer progression by evaluating the effects of a2V knock down on tumor cells. In this study, we have successfully deleted a2V gene in mouse 4T1 breast cancer cells using shRNA mediated knock down. These knock down cell lines are co-cultured with macrophages to evaluate previously observed immuno-modulatory effect of a2NTD. In addition, a2V knock down cells are injected into the Balb/c mice to generate tumors. The effect of a2V gene deletion on tumor progression and immune responses are evaluated in mice. We show that in the absence of a2V (finally a2NTD) growth and progression of tumor are suppressed by dominated host immune responses. Citation Format: Gajendra K. Katara, Arpita Kulshrestha, Mukesh Jaiswal, Alice Gilman-Sachs, Kenneth D. Beaman. Vacuolar ATPase subunit a2 is associated with immunosuppression in cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4097. doi:10.1158/1538-7445.AM2014-4097
One year treatment with almitrine improves hypoxaemia but does not increase pulmonary artery pressure in COPD patients
Authors: E Weitzenblum, F Schrijen, M Apprill, C Prefaut, JC Yernault
Journal: European Respiratory Journal (1991)

Almitrine bismesylate, a chemoreceptor agonist, improves hypoxaemia in a high percentage of chronic obstructive pulmonary disease (COPD) patients and its long-term use may thus be of interest in these patients. The course of pulmonary haemodynamics during a one year treatment was investigated in severe COPD patients (forced expiratory volume in one second FEV1 = 1,040 +/- 80 SEM ml) with persistent hypoxaemia (initial arterial oxygen tension (PaO2) in the range 6.6-8.6 kPa (50-65 mmHg]. Patients were given either almitrine (A, n = 27), 100 mg.day-1, during two consecutive months per quarter followed by a one month wash-out period (intermittent "schedule"), or placebo (P, n = 18) with the same schedule. Eleven patients in group A and 8 in group P could not complete the one year study because of lack of compliance, worsening of respiratory insufficiency, or for other reasons. In the remaining patients, PaO2 significantly increased in group A (n = 16) from 7.6 +/- 0.1 to 8.3 +/- 0.2 kPa (56.9 +/- 1.0 to 62.7 +/- 1.7 mmHg) (p less than 0.001) but not in group P (n = 10) from 7.5 +/- 0.3 to 7.9 +/- 0.3 kPa (56.1 +/- 2.3 to 59.1 +/- 2.1 mmHg). PaCO2 did not significantly change in either group. Pulmonary artery mean pressure (PAP) was stable in both groups: from 26.8 +/- 2.1 to 25.4 +/- 1.9 mmHg in group A, and from 20.6 +/- 1.1 to 20.9 +/- 1.5 mmHg in group P.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence-Informed Clinical Practice Recommendations for Treatment of Type 1 Diabetes Complicated by Problematic Hypoglycemia
Authors: Pratik Choudhary, Michael R. Rickels, Peter A. Senior, Marie-Christine Vantyghem, Paola Maffi, Thomas W. Kay, Bart Keymeulen, Nobuya Inagaki, Frantisek Saudek, Roger Lehmann, Bernhard J. Hering
Journal: Diabetes Care (2015)

Problematic hypoglycemia, defined as two or more episodes per year of severe hypoglycemia or as one episode associated with impaired awareness of hypoglycemia, extreme glycemic lability, or major fear and maladaptive behavior, is a challenge, especially for patients with long-standing type 1 diabetes. Individualized therapy for such patients should include a composite target: optimal glucose control without problematic hypoglycemia. Therefore, we propose a tiered, four-stage algorithm based on evidence of efficacy given the limitations of educational, technological, and transplant interventions. All patients with problematic hypoglycemia should undergo structured or hypoglycemia-specific education programs (stage 1). Glycemic and hypoglycemia treatment targets should be individualized and reassessed every 3–6 months. If targets are not met, one diabetes technology—continuous subcutaneous insulin infusion or continuous glucose monitoring—should be added (stage 2). For patients with continued problematic hypoglycemia despite education (stage 1) and one diabetes technology (stage 2), sensor-augmented insulin pumps preferably with an automated low-glucose suspend feature and/or very frequent contact with a specialized hypoglycemia service can reduce hypoglycemia (stage 3). For patients whose problematic hypoglycemia persists, islet or pancreas transplant should be considered (stage 4). This algorithm provides an evidence-informed approach to resolving problematic hypoglycemia; it should be used as a guide, with individual patient circumstances directing suitability and acceptability to ensure the prudent use of technology and scarce transplant resources. Standardized reporting of hypoglycemia outcomes and inclusion of patients with problematic hypoglycemia in studies of new interventions may help to guide future therapeutic strategies.
Multivitamin/Mineral Food Supplements Containing Vitamin B<sub>12</sub>May Also Contain Analogues of Vitamin B<sub>12</sub>
Authors: V Herbert, G Drivas, R Foscaldi, C Manusselis, N Colman, S Kanazawa, K Das, M Gelernt, B Herzlich, J Jennings
Journal: New England Journal of Medicine (1982)
Research is stifled by "regulation and conservatism," conference hears
Authors: A. Gulland
Journal: BMJ (2015)

The medical research community has failed to respond to the threat of infectious diseases, Jeremy Farrar, director of the Wellcome Trust, has warned. Speaking in London at the scientific conference for charity Medecins Sans Frontieres, Farrar said that medical research was stifled by regulation and conservatism and hampered by fragmentation.

He used the example of Middle East respiratory syndrome coronavirus, research into which has moved on very little since the first case was diagnosed in 2013. “We are now in May 2015 and we don’t understand the epidemiology, we don’t understand the animal reservoir, we don’t understand the transmission dynamic, we have not worked out how to treat individual patients or prevent secondary transmission, and we do not have a vaccine,” he said.

“We need much more innovation in the design of research. We haven’t moved human study design on in the past 20 …
Liver X receptors balance lipid stores in hepatic stellate cells through Rab18, a retinoid responsive lipid droplet protein
Authors: Fiona O'Mahony, Kevin Wroblewski, Sheila M. O'Byrne, Hongfeng Jiang, Kara Clerkin, Jihane Benhammou, William S. Blaner, Simon W. Beaven
Journal: Hepatology (2014)

Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxr αβ −/− mice have increased lipid droplet (LD) size, but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts activation. Primary HSCs from Lxr αβ −/− and wild‐type mice were profiled by gene array during in vitro activation. Lipid content was quantified by high‐performance liquid chromatography and mass spectroscopy. Primary HSCs were treated with nuclear receptor ligands, transfected with small interfering RNA and plasmid constructs, and analyzed by immunocytochemistry. Lxr αβ −/− HSCs have increased cholesterol and retinyl esters. The retinoid increase drives intrinsic retinoic acid receptor signaling, and activation occurs more rapidly in Lxr αβ −/− HSCs. We identify Rab18 as a novel retinoic acid‐responsive, LD‐associated protein that helps mediate stellate cell activation. Rab18 mRNA, protein, and membrane insertion increase during activation. Both Rab18 guanosine triphosphatase activity and isoprenylation are required for stellate cell LD loss and induction of activation markers. These phenomena are accelerated in Lxr αβ −/− HSCs, where there is greater retinoic acid flux. Conversely, Rab18 knockdown retards LD loss in culture and blocks activation, just like the functional mutants. Rab18 is also induced with acute liver injury in vivo . Conclusion : Retinoid and cholesterol metabolism are linked in stellate cells by the LD‐associated protein Rab18. Retinoid overload helps explain the profibrotic phenotype of Lxr αβ −/− mice, and we establish a pivotal role for Rab18 GTPase activity and membrane insertion in wild‐type stellate cell activation. Interference with Rab18 may have significant therapeutic benefit in ameliorating liver fibrosis. (H epatology 2015;62:615–626
Assessment of co-exposure to allergenic pollen and air pollution in Copenhagen
Authors: Vivi Schlünssen, Pia Ørby, Robert Peel, Carsten Skjøth, Jakob Bønløkke, Thomas Ellermann, Andreas Brændholt, Torben Sigsgaard, Ole Herten
Journal: European Respiratory Journal (2014)

Background .Co-exposure to air pollutants and allergenic pollen can elicit or exacerbate a number of conditions in susceptible individuals, including allergic airway diseases. Both concentrations and diurnal patterns are relevant when assessing potential health effects.   Methods. To assess which pollutants may be of particular relevance when investigating co-exposure with pollen, we examined yearly variation and diurnal patterns of pollutants on days with high pollen levels, and also for the remaining part of the pollen season. This analysis included measurements of grass and birch pollen, sulphur dioxide (SO 2 ), ozone (O 3 ), nitrogen dioxide (NO 2 ) and particulate matter (PM) in the period 1997-2012.   Results. O 3  concentrations were found to be higher on peak pollen days and high O 3  concentrations coincide both seasonally and diurnally with high pollen counts, potentially leading to clinically relevant simultaneous co-exposure. NO 2  and SO 2  did not appear to coincide in concentration peaks with pollen counts, and concentrations were well below potential thresholds for adjuvant effects to the allergic reaction. Neither diurnal nor seasonal concentration peaks in PM were found to coincide with peaks in pollen concentrations, however daily average PM concentrations were higher on peak pollen days than on non-peak days.   Conclusion.  This study indicates that when considering co-exposure effects from pollen and pollutants, O 3  appears to be the most relevant pollutant to further examine for clinical effects of simultaneous co-exposures.
Depletion of T -Lymphocytes in Donor Marrow With Pan-T Monoclonal Antibodies and Complement for Prevention of Acute Graft-Versus-Host Disease: A Pilot Study on 29 Patients1
Authors: P. Herve
Journal: JNCI Journal of the National Cancer Institute (1986)

A cooperative study was done on ex vivo treatment of bone marrow for the prevention of acute graft-versus-host disease (GvHD), in which either CD2-CD5-CD7 (14 patients) or CD2-CD3 (15 patients) monoclonal antibody cocktail and complement were used. In this study, 29 patients (12 female, 17 male; average age, 22-1/2 yr) received T-cell-depleted allograft through complement cytolysis, 26 from HLA-identical donors and 3 from HLA-mismatched donors. All of the patients had malignant disease with poor prognosis; 21 had acute leukemia, 7 had chronic granulocytic leukemia, and 1 had multiple myeloma. After bone marrow transplantation (BMT), GvHD prophylaxis was maintained in 12 patients (group 1), was stopped at day 11 in 6 patients (group 2), and was not administered to 11 patients (group 3). The treatment removed 92.65 +/- 5.36% of donor bone marrow T-cells with one round of complement lysis. Of 3 patients who received mismatched transplant, 2 did not achieve engraftment. Engraftment was achieved in all of the patients who had matched BMT. Two patients had acute GvHD, 1 with grade 2 in group 1, and 1 with grade 3 in group 3. No patient has developed chronic GvHD; for 9 patients, the follow-up is longer than 6 months. Five patients relapsed within 6 months after BMT. Eighteen patients are alive and well in complete remission, with an average follow-up of 7.5, 10.6, and 2.7 months for patients in groups 1, 2, and 3, respectively.
Impact of a dedicated infusion clinic for acute management of adults with sickle cell pain crisis
Authors: Sophie Lanzkron, C. Patrick Carroll, Peter Hill, Mandy David, Nicklaine Paul, Carlton Haywood
Journal: American Journal of Hematology (2015)

Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ(2) tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model.
Bronchial gamma delta T-lymphocytes and expression of heat shock proteins in mild asthma
Authors: I Fajac, GL Roisman, J Lacronique, BS Polla, DJ Dusser
Journal: European Respiratory Journal (1997)

Heat shock proteins (HSPs), which are important targets for gammadelta T-lymphocytes, are thought to play a role in inflammatory and immune diseases. The purpose of this study was to characterize, in asthma, the presence and distribution of alphabeta and gammadelta T-lymphocytes and of hsp60, hsp70 and hsp90 in bronchial biopsies, and to seek for a co-localization of gammadelta T-cells and HSPs. Ten subjects with mild atopic asthma and nine control subjects underwent fibreoptic bronchoscopy and bronchial biopsies, to which specific monoclonal antibodies and immunohistochemical techniques were applied. T-lymphocytes present in bronchi both of asthmatic and control subjects were predominantly of the alphabeta T-cell receptor phenotype (median 642 cells x mm(-2) (range 85-1,510 cells x mm(-2)), and 855 cells x mm(-2) (286-2,424 cells x mm(-2)), respectively), whereas, gammadelta T-lymphocytes were always rare (median 26 cells x mm(-2) (range 0-114 cells x mm(-2)), and 0 cells x mm(-2 (0-57 cells x mm(-2), respectively). Both in asthmatic and control subjects, bronchial epithelium was positive for hsp60, hsp70 and hsp90. There was no significant difference in the percentages of positive epithelial cells between asthmatic and control subjects. No co-localization of HSPs and gammadelta T-cells was observed. Our findings do not support the hypothesis that heat shock proteins and gammadelta T-cells play an important role in inflammatory and immune responses in mild asthma.
Anticoagulation in cancer patients in hospice
Authors: H. M. Holmes, K. T. Bain, R. Luo, A. Zalpour, E. Bruera, J. S. Goodwin
Journal: Journal of Clinical Oncology (2009)

e20509 Background: Low-molecular weight heparin (LMWH) is preferred over warfarin in patients with thromboembolic disease and active cancer, but no guidelines exist in hospice. Although warfarin may be less safe in hospice patients, hospices may prefer to provide warfarin due to lower cost and less invasiveness compared to LMWHs. We sought to identify disparities in the use of warfarin vs. LMWHs in cancer patients enrolled in hospice. Methods: We analyzed a dataset from a national pharmacy provider for more than 800 hospices. We identified patients with a terminal diagnosis of cancer who were enrolled and died in hospice in 2006 and who were prescribed warfarin or LMWH. Patient characteristics included age, gender, race, cancer diagnosis, length of hospice service, and number of comorbidities. For descriptive comparisons, the Kruskal-Wallis test was used for continuous variables, and the Chi-square test was used for categorical variables. Results: Of 54,764 patients with cancer admitted and deceased in 2006, 3874 (7.1%) were prescribed warfarin, and 1137 (2.1%) were prescribed LMWH. Patients prescribed warfarin (n=576) or enoxaparin (n=5) for treatment of atrial arrhythmias were excluded. The mean age was 70.6 years for warfarin and 64.8 years for LMWH (p&lt;0.0001). The mean and median lengths of service, respectively, were 43.6 days and 23.0 days for warfarin and 35.0 and 18.0 days for LMWH, (p&lt;0.0001). There were no differences for gender, and a higher proportion of white patients were prescribed warfarin. Patients prescribed warfarin had an average of 2.1 comorbid conditions, versus 1.6 conditions for LMWH (p&lt;0.0001). Cancer diagnoses were significantly different between the two groups, with a higher proportion of patients with lung and prostate cancer taking warfarin. Conclusions: Patients prescribed warfarin were older, had more comorbidities, and a longer length of service than patients prescribed LMWHs. Further research is needed to determine the impact of anticoagulation on outcomes, especially cost and quality of life, for cancer patients in hospice. This study raises the need to establish guidelines for the appropriateness of anticoagulation in hospice patients with cancer. No significant financial relationships to disclose.