tbuckley/cabot-search huggingface dataset:
A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients.
Authors: F G LeVeque, M Montgomery, D Potter, M B Zimmer, J W Rieke, B W Steiger, S C Gallagher, C C Muscoplat
Journal: Journal of Clinical Oncology (1993)

To determine the efficacy and safety of pilocarpine hydrochloride for symptomatic relief of postradiation xerostomia symptoms and for saliva production in patients with head and neck cancer.One hundred sixty-two head and neck cancer patients who had received at least 40 Gy of radiation (117 patients had received > 60 Gy) with clinically significant xerostomia were enrolled onto a randomized, double-blind, placebo-controlled, multi-center clinical investigation. Patients received 2.5-mg tablets for the first 4 weeks, 5.0-mg tablets for the second 4 weeks, and 10.0-mg tablets for the last 4 weeks of the 12-week study. Patients were allowed to titrate pilocarpine or placebo for improvement in symptoms or to reduce side effects. Patients were evaluated for symptomatic relief by questionnaires and visual analog scales (VAS), and for saliva production by sialometry.Pilocarpine produced a significant improvement (P = .035) in overall global assessments compared with placebo. There was a statistically significant (P = .020) decreased use of oral comfort agents such as artificial saliva, hard candy, and water. Values for symptomatic improvement in dryness approached significance (P = .057). There were statistically significant postdose improvements in whole and parotid salivary flow in pilocarpine treatment groups versus placebo. All pilocarpine dosages tested were judged to be safe. Adverse experiences were primarily sweating, rhinitis, headache, nausea, and urinary frequency, with the most common side effect being mild to moderate sweating. There were no serious drug-related adverse experiences in any of the pilocarpine treatment groups.It is concluded that pilocarpine produces clinically significant benefits for the symptomatic treatment of postradiation xerostomia. Best results were obtained with continuous treatment for 8 to 12 weeks with doses greater than 2.5 mg three times per day.
Antituberculosis fixed multi-dose combination and single drug therapy in active tuberculosis: What is the benefit?
Authors: Amina Kotti, Hafaoua Daghfous, Wafa Bouhawel, Olfa Kahloul, Fatma Tritar
Journal: European Respiratory Journal (2011)

Background:  Fixed dose combinations (FDCs) in tuberculosis (TB) therapy reduce the number of tablets to be consumed, simplify the medication regimen and potentially improve compliance.   Aim of study:  Compare the efficacy and acceptability of anti-TB FDCs as single tablets (ST) in patients with active TB.   Patients and methods:  A total of consecutive 94 patients (57 men and 37 women; mean age 38,1±3,3 years) were randomly distributed into 2 groups: trial group (n= 41) patients treated daily with anti-TB FDCs and control group (n= 53) treated with standardized regimen (single tablets).   Results:  Stratified analyses showed a similar pattern for all the group dermographic, clinical and radiologic finding. The dosage of isoniazid, pyrazinamid and ethambutol was adequate in all patients. For rifampicin, dosage was statistically too low in trial group (p= 0,04). Serious adverse events were noted in 39% cases of trial group vs 11,5% cases in control group. According of cutaneous reactions (7,3% vs 5,7%) and toxic hepatitis (7,3% vs 3,7%) there was no statistically difference in 2 groups. Hematologic effects (21% vs 0%) were stastically higher in trial group (p= 0,018). All patients had a successful outcome. At 2 months of treatment, 50% of patients in trial group achieved sputum conversion vs 43% patients in control group without statistically significant difference. Radiologic sequellae was noted in 51% in trial group vs 36% in control group.   Conclusion:  The efficacy of the anti-TB FDCs regimen was non-inferior to that of the standardized regimens. But, hematologic effects were significantly higher in the group of patients treated with anti-TB FDCs.
Erlotinib (E) in elderly pts with NSCL: Experience at a tertiary referral center
Authors: Alexios Strimpakos, Dimitris Vassos, Antonis Vassias, Sotiris Tsimboukis, Paraskevi Boura, Sofia Tsagkouli, Marios Zontanos, Konstantinos Syrigos
Journal: European Respiratory Journal (2013)

Background:Besides chemotherapy, E is an option in NSCLC pts especially in those with EGFR mutations. Elderly pts enrolled in trials are fit without cM but in clinical practice most suffer from cM. Methods: Medical records of 1221 pts diagnosed with NSCLC between 2008-2012 were screened. We examined pts of 75 yrs for demographics, clinical data and Tx details. Results: 233/1221 NSCLC pts received E at any line. 53/233 (23%) were 75 yrs old. Male:female ratio was 34:19, median age 79 yrs (range 75-88). NSCLC subtypes included 31 adenoca, 8 squamous, 9 NOS and 5 others. 50/53 pts had cM (≥2 in 46 pts, 1 in 4pt). Main cM were cardiovascular disease (n=41), COPD (n=14), other cancer (n=10) and diabetes (n=8). 8 pts were tested for EGFR mutations (5 -ve, 3 +ve). Performance Status was satisfactory (ECOG 0-1) in 8 pts and poor (2-3) in 45pts. 8pts were treated with E 100mg and 45 pts with E 150mg (12 pts needed dose reduction). Complete follow up data were found in 46pts. Mean duration of treatment was 79 days (range 9-662). 35/46 pts experienced side effects which led to treatment discontinuation in 12pts. Pts with abnormal creatinine clearance (n=13) were more likely to stop treatment due to s.e (6/13 versus 6/33). 17/46 pts (37%) achieved disease control (5 PR, 12 SD) and a time to progression (TTP) of 157 days while 22/46 pts had PD as best response (TTP 49d, range 19-88, CI 44,67-64,97). 7pts were not evaluable (stopped Tx due to s.e). All EGFR+ve pts had disease control (2PR, 1SD). Conclusions: E is a valuable option in elderly NSCLC patients with co-morbidities, especially if they harbor EGFR mutations. Impaired renal function might be associated with side effects and earlyTx discontinuation.
A theme issue by, for, and about Africa
Authors: Marina Giuliano, Michele Magoni, Luciana Bassani, Pius Okong, Praxedes Kituka Namaganda, Saul Onyango
Journal: BMJ (2005)

A theme issue by, for, and about Africa Results from Ugandan programme preventing maternal transmission of HIVEditor-Since the efficacy of antiretroviral drugs in preventing HIV transmission from mother to child was first shown, much effort has been devoted in many countries in Africa to implement sustainable regimens. [1]2][3][4] To identify potential reasons affecting uptake we evaluated the five year performance of a programme at St Francis Hospital Nsambya in Kampala, Uganda.The programme included voluntary counselling and confidential HIV testing for pregnant women and administration of antiretroviral prophylaxis in the peripartum period (zidovudine or nevirapine) for HIV positive women.Overall 24 133 women received counselling, 76% (18 384) agreed to be tested, and 2011 (10.9%) were HIV positive; 1341 (66.7% of the HIV positive women) were enrolled in the programme and received antiretroviral drugs.Acceptance of the test increased from 72.7% (9103/12 524) in 2000-2 to 79.9% (9281/11 609) in 2003-4, when a drug access programme became available in the hospital.Acceptance of the test and enrolment in the programme were lower in married or cohabitating women (test acceptance rate 72.9% (7735/10 605)) than single women (78% (860/1106)), indicating that the fear of being identified as HIV positive in the family is still a strong limiting factor and that men could have an important role.Acceptance of the test was lower in women belonging to the local tribe in Kampala (Baganda), probably because of fear of being recognised by hospital health workers.Higher education was associated with a lower prevalence of HIV and a higher enrolment in the programme, confirming that education can have a key role not only in protecting against HIV but also in allowing HIV positive people to benefit from existing measures against the spread of HIV.
Association of chemokine CXC ligand 12 gene polymorphism (rs1746048) with cardiovascular mortality in patients with rheumatoid arthritis: results from the Norfolk Arthritis Register: Table 1
Authors: Ibrahim Ibrahim, Jennifer Humphreys, Ibtisam Mokhtar, Tarnya Marshall, Suzanne Verstappen, Deborah Symmons, Sebastien Viatte, Anne Barton, Darren Plant
Journal: Annals of the Rheumatic Diseases (2015)

Patients with rheumatoid arthritis (RA) are at increased risk of premature mortality, with cardiovascular disease (CVD) forming the primary cause.1 

Previous studies have identified correlations between genetic polymorphisms located both inside2 and outside3 the human leucocyte antigen locus with increased risk of CVD morbidity and mortality, independent of traditional CVD risk factors.

A recent genome-wide association study identified a genetic variant (rs1746048) proximal to the CXCL12 gene on chromosome 10q11.21, that is strongly associated with coronary artery disease (p=8.1×10−9),4 increased carotid intimal–medial thickness5 and plasma levels of CXCL12.6 Several studies have highlighted an important role for CXCL12 in RA by demonstrating increased levels of CXCL12 in synovial fluid, as well as upregulation of CXCL12 mRNA in synovial fibroblasts, which may contribute to sustained inflammation.7 However, a large study of Spanish patients with established RA did not detect an association with CVD outcome and a …
Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer.
Authors: P M Ravdin, H A Burris, G Cook, P Eisenberg, M Kane, W A Bierman, J Mortimer, E Genevois, R E Bellet
Journal: Journal of Clinical Oncology (1995)

PURPOSE The purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone. PATIENTS AND METHODS Docetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen. RESULTS Objective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxicity in this study was grade 4 neutropenia, which occurred in 95% of patients. Other clinically significant nonhematologic side effects included stomatitis, skin reactions, neurosensory changes, asthenia, and fluid retention. Patients who received dexamethasone premedication had a later onset of fluid retention than those who did not receive dexamethasone (onset at a median cumulative docetaxel dose of 503 mg/m2 and 291 mg/m2, respectively). CONCLUSION Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.
ACTION SPECTRA IN IDIOPATHIC SOLAR URTICARIA..
Authors: HAZEL IVE, JENNIFER LLOYD, I. A. MAGNUS
Journal: British Journal of Dermatology (1965)

Journal Article ACTION SPECTRA IN IDIOPATHIC SOLAR URTICARIA.: A Study OF 17 Cases With a Monochromator. Get access HAZEL IVE, HAZEL IVE Institute of Dermatology, St. John's Hospital for Diseasea of the Skin, Homerton Grove London, E.9 Search for other works by this author on: Oxford Academic Google Scholar JENNIFER LLOYD, JENNIFER LLOYD Institute of Dermatology, St. John's Hospital for Diseasea of the Skin, Homerton Grove London, E.9 Search for other works by this author on: Oxford Academic Google Scholar I. A. MAGNUS I. A. MAGNUS Institute of Dermatology, St. John's Hospital for Diseasea of the Skin, Homerton Grove London, E.9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 5, 1 May 1965, Pages 229–243, https://doi.org/10.1111/j.1365-2133.1965.tb14637.x Published: 01 May 1965
Severe Adrenal Suppression by Steroid Nasal Drops
Authors: Geoffrey Gill, Andrew Swift, Alan Jones, David Strain, Philip Weston
Journal: Journal of the Royal Society of Medicine (2001)

Systemic absorption of corticosteroids from inhaled and topical preparations can result in adrenal underactivity1. When systemic effects from nasal steroid drops have been reported2,3,4,5,6,7, the features were usually cushingoid rather than addisonian.
A Phase 1b, Open-Label, Dose-Finding Study of Ruxolitinib in Patients with Myelofibrosis (MF) and Baseline Platelet Counts from 50 × 109/L to 99 × 109/L (The EXPAND Study)
Authors: Peter te Boekhorst, Claire N. Harrison, Heinz Gisslinger, Dietger Niederwieser, Viktoriya Stalbovskaya, Edric Atienza, Prashanth Gopalakrishna, Alessandro M. Vannucchi
Journal: Blood (2014)
Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment
Authors: Xing-Lin Tan, Yue-Qiang Xue, Tao Ma, Xiaofang Wang, Jing Jing Li, Lubin Lan, Kafait U. Malik, Michael P. McDonald, Alejandro M. Dopico, Francesca-Fang Liao
Journal: Molecular Neurodegeneration (2015)

Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS+/- mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS+/- mice as early as 3–6 months of age but not in eNOS+/+ mice at any age. Remarkably, vascular occlusions in eNOS+/- mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS+/- mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS+/- mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.
Serological study of the 2009 pandemic due to influenza A H1N1 in the metropolitan French population
Authors: J. Delangue, N. Salez, L. Ninove, A. Kieffer, C. Zandotti, M. Seston, B. Lina, A. Nougairede, R. Charrel, A. Flahault, X. de Lamballerie
Journal: Clinical Microbiology and Infection (2011)
MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer
Authors: Hyun Jin Bae, Kwang Hwa Jung, Jung Woo Eun, Qingyu Shen, Hyung Seok Kim, Se Jin Park, Woo Chan Shin, Hee Doo Yang, Won Sang Park, Jung Young Lee, Suk Woo Nam
Journal: Journal of Hepatology (2015)
Abstract 106: Does Early Post-Cardiac Arrest Illness Severity Affect the Association Between Immediate Cardiac Catheterization and Improved Outcome?
Authors: Joshua C Reynolds, Jon C Rittenberger, Clifton W Callaway
Journal: Circulation (2013)

Objectives: Immediate cardiac catheterization (CATH) is recommended for post cardiac arrest patients with STEMI or suspicion for acute cardiac ischemia. However, it is unclear if early CATH is bene...
Relational Processes and DSM-V: Neuroscience, Assessment, Prevention, and Treatmentedited by Steven R.H. Beach, Ph.D., Marianne Z. Wamboldt, M.D., Nadine J. Kaslow, Ph.D., Richard E. Heyman, Ph.D., Michael B. First, M.D., Lynn G. Underwood, Ph.D., and David Reiss, M.D. Arlington, Va., American Psychiatric Publishing, 2006, 293 pp., $59.00.
Authors: THOMAS F. ANDERS
Journal: American Journal of Psychiatry (2007)
Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.
Authors: V Conter, M Aricò, M G Valsecchi, C Rizzari, A M Testi, C Messina, P G Mori, R Miniero, R Colella, G Basso
Journal: Journal of Clinical Oncology (1995)

PURPOSE To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy. PATIENTS Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], &lt; 0.8); intermediate risk (IR) were patients with an RI &gt; or = 0.8 but less than 1.2; and high risk (HR) were those with an RI &gt; or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients. RESULTS Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group. CONCLUSION Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.
A retrospective study of depressive illness in patients with pulmonary hypertension (PH) at a specialist centre
Authors: Lisa Parfitt, Philip Marino, Carl Harries, Kostas Dimopoulos, John Wort
Journal: European Respiratory Journal (2014)

Background:  PH is a life limiting and severely debilitating condition with no cure. The emotional well being of these patients is important as many can develop anxiety and depression, leading to significant impairment in quality of life (QOL). The current PH guidelines acknowledge the importance of psychological illness and advocate referral to psychological services (1). Other than overall QOL assessment, specific psychological assessment is infrequently performed clinically and a literature review indicates this aspect of care is under researched in the UK.   Methods:  A retrospective study was conducted in 115 PH patients at the Royal Brompton Hospital, with the aim to identify the extent and nature of depressive illness and current clinical practice in this group.   Results:  We found screening tools for depression were not used in routine practice. 19% of patients were taking antidepressants and referral for psychological intervention was documented in 7% of patients. Social and physical factors were highlighted as having the potential to influence the development of depressive symptoms such as occupational and marital status and functionality, which were most evident in those with PAH etiologies and lung disease.   Conclusion:   This study highlights a potential unmet need in assessing and managing depressive disorders in PH patients. Further research is required to better understand, screen and treat these significant conditions. Ultimately, referral to psychotherapy services should be promoted to ensure that these needs are addressed.   Reference:   1. Galie, N et al, Guidelines for the diagnosis and treatment of PH,  EHJ 2009,  30 (20), 2493-2537.
BAPX-1/NKX-3.2 Acts as a Chondrocyte Hypertrophy Molecular Switch in Osteoarthritis
Authors: Marjolein M. J. Caron, Pieter J. Emans, Don A. M. Surtel, Peter M. van der Kraan, Lodewijk W. van Rhijn, Tim J. M. Welting
Journal: Arthritis & Rheumatology (2015)

Objective Osteoarthritis (OA) development involves a shift of the articular chondrocyte phenotype toward hypertrophic differentiation via still poorly characterized mechanisms. The purpose of this study was to test our hypothesis that the function of BAPX‐1/NKX‐3.2 is impaired in OA chondrocytes and leads directly to loss of hypertrophic protection of the articular chondrocyte, which is central in the changing chondrocyte phenotype that drives OA. Methods Human articular chondrocytes (HACs; from healthy and OA donors) and SW‐1353 chondrocytic cells were exposed to bone morphogenetic protein 7 (BMP‐7), interleukin‐1β (IL‐1β), tumor necrosis factor, or OA synovial fluid (SF; 20% [volume/volume]). Loss‐of‐function and gain‐of‐function experiments for BAPX‐1/NKX‐3.2 were performed. Mouse experimental models of OA were used, and (immuno)histochemistry of tissue sections was performed. Gene and protein expression of BAPX‐1/NKX‐3.2 and chondrogenic, hypertrophic, and OA‐related mediators were determined by real‐time quantitative polymerase chain reaction analysis and immunoblotting. In addition, alkaline phosphatase (AP) activity and prostaglandin E 2 levels were measured. Results BAPX‐1/NKX‐3.2 expression correlated negatively with expression of chondrocyte hypertrophic markers (RUNX‐2, COL10A1, AP), cartilage‐degrading enzymes (matrix metalloproteinase 13, ADAMTS‐5), and mediators of inflammation (cyclooxygenase 2, IL‐6) in healthy and OA chondrocytes, as well as in OA induced chondrocytes. BAPX‐1/NKX‐3.2 positivity was diminished in articular chondrocytes in the knee joints of mice with experimental OA. Knockdown of BAPX‐1/NKX‐3.2 in HACs did not influence the expression of SOX9, COL2A1, or aggrecan, but led to an acute hypertrophic shift in the HAC phenotype. Overexpression of BAPX‐1/NKX‐3.2 decreased hypertrophic gene expression in HACs. Furthermore, the hypertrophic OA chondrocyte phenotype could be counteracted by overexpression of BAPX‐1/NKX‐3.2 and by BMP‐7 in a BAPX‐1/NKX‐3.2 dependent manner. Conclusion Our findings indicate that BAPX‐1/NKX‐3.2 is a molecular switch that is involved in controlling the hypertrophic phenotype of the postdevelopmental (OA) articular chondrocyte.
Prevalence of mitral valve prolapse in bipolar affective disorder
Authors: A J Giannini, W A Price, R H Loiselle
Journal: American Journal of Psychiatry (1984)

Of 32 patients with unipolar or bipolar affective disorder, significantly more bipolar patients had mitral valve prolapse. The prevalence of mitral valve prolapse among bipolar patients was also significantly greater than that in the general population.