tbuckley/cabot-search huggingface dataset:
Combined Tamoxifen and Luteinizing Hormone-Releasing Hormone (LHRH) Agonist Versus LHRH Agonist Alone in Premenopausal Advanced Breast Cancer: A Meta-Analysis of Four Randomized Trials
Authors: J. G.M. Klijn, R.W. Blamey, F. Boccardo, T. Tominaga, L. Duchateau, R. Sylvester
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. PATIENTS AND METHODS: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials. RESULTS: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio = 0.67). CONCLUSION: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.
Controversies in Management: Case for early treatment is not established
Authors: D. Chadwick
Journal: BMJ (1995)

The most important question in epilepsy is whether antiepileptic drugs not only reduce susceptibility to seizures in someone with epilepsy but also modify the natural course of the condition. The concept of a process of epileptogenesis is strongly grounded in the large volume of work on the kindling model of epilepsy1 and is supported by some circumstantial clinical evidence. However, I believe that the clinical evidence weighs against early treatment with antiepileptic drugs affecting natural course at a practical level.

Epilepsy is a group of disorders in which seizures occur and not a homogeneous disease entity. The response to antiepileptic drugs may therefore differ. The issue of heterogeneity can be partly addressed by looking at the prognosis for epilepsy syndromes and the likelihood of their being influenced by antiepileptic drugs. One clear cut children's epilepsy syndrome is that of benign rolandic epilepsy, in which focal motor seizures, usually affecting the face, throat, and arm, occur during sleep in children between the ages of 7 and 12. Seizures stop by mid-adolescence,2 and many paediatricians no longer give such children antiepileptic drugs since the outcome seems to be entirely benign whether or not treatment is given.

A rather different picture arises in …
The critical role of interferon-gamma signaling in the respiratory immune response to influenza infection
Authors: David M. Kemeny, Nayana Prabhu, Adrian W. Ho, Kenneth H. Wong, Benson C.L. Chua, Paul E. Hutchinson, Baalasubramanian Sivasankar
Journal: European Respiratory Journal (2013)

We investigated the role of IFN-γ signaling on the resolution of lung inflammation and immune memory. IFN-γ-/- and IFN-gR-/- mice were infected with influenza H1N1(PR8). Bronchoalveolar lavage(BAL) was collected and eosinophils identified as SINGLEC-F+ve and CD11c-ve and neutrophils as Ly6G+ve and CD11c-ve. Influenza-specific CD8 T cells were identified with H2Db-NP366-374 tetramers. Cytokines were determined by ELISA, influenza-specific antibodies by red cell agglutination inhibition assay and mucus production by Periodic Acid Schiff staining. IFN-γ-/- mice produced a greater lung CD8 T cell response (WT 80,000, IFN-γ-/- 300,000 NP366-374 CD8 T cells p
Hepatitis B Virus Infection and Primary Hepatocellular Carcinoma 2 3
Authors: Edward Tabor, Robert J. Gerety, Charles L. Vogel, Anne C. Bayley, Peter P. Anthony, Chao H. Chan, Lewellys F. Barker
Journal: JNCI Journal of the National Cancer Institute (1977)

Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls.
Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency.
Authors: D A Williams, W Tao, F Yang, C Kim, Y Gu, P Mansfield, J E Levine, B Petryniak, C W Derrow, C Harris, B Jia, Y Zheng, D R Ambruso, J B Lowe, S J Atkinson, M C Dinauer, L Boxer
Journal: Blood (2000)
Tropical pulmonary eosinophilia: An unusual cause of childhood wheezing: An experience from a tertiary care hospital from North India
Authors: Ankit Parakh, Varinder Singh, B. Rath, Jagdish Chandra
Journal: European Respiratory Journal (2014)

Introduction:  Tropical Pulmonary Eosinophilia (TPE) is a pulmonary manifestation of filarial infection seen in many parts of India, usually in adults. Childhood description of disease is rare.  Methods:  Children ( 3000/microL, reticulonodular / fleeting pulmonary infiltrates and clinical response to a course of Diethylcarbamazine (DEC).  Results : Details from 8 children is presented here. The median age was 6y (3 children  Conclusion:  TPE is an uncommon disease infrequently described in children with virtually no reports in
Prevalence of fluoroquinolone resistance in mycobacterium tuberculosis in a tertiary care hospital in India
Authors: Madhav Kale, Parag Khatavkar, Meenakshi Satpute, Nilima Telang
Journal: European Respiratory Journal (2014)

INTRODUCTION:  Fluoroquinolones(FQ) are important drugs in treatment of drug resistant tuberculosis. In recent years, there is increase in FQ resistance due to suboptimal use of second line drugs in drug resistant tuberculosis and misuse as empiric therapy for respiratory infections. It is common in India that a suspected community acquired pneumonia treated with monotherapy with FQ later turns out to be pulmonary tuberculosis. Such a short exposure can induce bacillary resistance to entire class of drugs.  AIMS:  To determine the prevalence of ciprofloxacin (CFX), levofloxacin(LFX) and moxifloxacin(MFX) resistance to  Mycobacterium tuberculosis (MTB)  METHOD:  During the period Jan. 2011 to Dec. 2013, all samples (pulmonary: sputum, BAL and extrapulmonary:lymph node, pleural fluid, CSF etc) which were culture positive for MTB, were retrospectively analyzed to assess the prevalence of CFX, LFX and MXF. Samples were cultured for MTB by radiometric method (MB/BacT Mycobacterium Detection System). Sensitivity tests were performed by conventional method on L.J. medium  RESULTS:  CONCLUSION:  During three year period, resistance to CFX has fallen posibly due to reduced usage, but that of MXF has increased possibly due to increased usage. The overall resistance to these drugs is low. Caution is advised to avoid indiscriminate use of these drugs.  REFERENCE:  Agarwal et al: Increasing incidence of fluoroquinolone-resistant  Mycobacterium Tuberculosis  in Mumbai, India.Int.J.Tuberc. Lung Dis 2009; 13(1):79-83.
Outcomes and complications of continuous intraspinal narcotic analgesia for cancer pain control.
Authors: D W Coombs, L H Maurer, R L Saunders, M Gaylor
Journal: Journal of Clinical Oncology (1984)

Preliminary reports of continuous intraspinal morphine analgesia have been enthusiastic regarding the resultant cancer pain control. Reports of continuous intraspinal infusion have not documented the duration of useful analgesia, need for concomitant analgesic therapies, or complication rates. Thus, the overall outcomes and complications of six chronic intrathecal and eight epidural morphine infusions were analyzed in the first 14 cancer pain patients implanted with continuous intraspinal morphine infusion reservoirs at this clinic. A five-point scale was used to assess the analgesic therapy required to maintain pain control during three consecutive intervals of intraspinal morphine infusion (zero to two months, two to six months, after six months). Comparison with pre-implant narcotic requirements revealed equal or reduced narcotic use for up to six months of therapy, with a definite trend toward escalation of intraspinal narcotics, systemic analgesia, and adjunctive procedures after two months. This occurred most likely due to narcotic tolerance and disease progression. Failure of pain control was the rule with continuous intraspinal morphine after six months. Three patients ultimately required neurolytic blocks. No clear difference was found in pain control requirements between epidural and intrathecal morphine infusion. No infection or respiratory depression occurred as a direct result of the intraspinal morphine implanted system.
Low dose aspirin may be used for prophylaxis
Authors: C. Nelson-Piercy, M. De Swiet
Journal: BMJ (1996)

develop the intermediate neurotoxic syndrome while other equally seriously intoxicated patients do not.Paraoxon polymorphism (the genetic capability of humans to detoxify organophos- phates), toxic liposolubility, and interaction with other toxins, among other possibilities, would contribute to the development of the intermediate neurotoxic syndrome in people with atypical butyrylcholinesterase.Therefore, pseudocholinesterase activity is worth studying in further epidemiological and toxicological follow up studies on pesticide intoxication, including those recommended by
Spironolactone in the Treatment of Idiopathic Hirsutism and the Polycystic Ovary Syndrome
Authors: D J Evans, C W Burke
Journal: Journal of the Royal Society of Medicine (1986)

Forty-eight hirsute women were treated with spironolactone 100 mg twice daily for 3 to 12 months. Both facial and body hirsuties improved by 30–40%, and there was a threefold reduction in frequency of local treatments such as waxing or shaving. Plasma testosterone fell by 30%, though the improvement in hirsuties grading did not correlate with the fall in plasma testosterone. Six subjects discontinued treatment because of lack of effect, and 4 because of menstrual disturbance. Spironolactone was equally effective in the treatment of idiopathic hirsutism and of the polycystic ovary syndrome.
Effect of MM-141 on gemcitabine and nab-paclitaxel potentiation in preclinical models of pancreatic cancer through induction of IGF-1R and ErbB3 degradation.
Authors: Emily Pace, Sharlene Adams, Adam Camblin, Michael Curley, Victoria Rimkunas, Lin Nie, Sergio Iadevaia, Gege Tan, Jason Baum, Akos Gabor Czibere, Alexey Lugovskoy
Journal: Journal of Clinical Oncology (2015)

289 Background: Gemcitabine, the first-line treatment for pancreatic cancer, has been improved by addition of nab-paclitaxel. However, patient response to this regimen is limited. Oncogenic insulin-like growth factor 1 (IGF-1) and heregulin (HRG) signaling are associated with increased cancer risk and decreased response to anti-metabolites and taxanes. Therefore, we explored MM-141, a novel bispecific antibody that blocks ErbB3 and IGF-1 receptor (IGF-1R) signaling, in combination with nab-paclitaxel and gemcitabine in preclinical models of pancreatic cancer. Methods: Combinations with MM-141, gemcitabine, and nab-paclitaxel were investigated in pancreatic cancer cell lines, in vitro and in vivo. The effects of MM-141, gemcitabine, and nab-paclitaxel on tumor growth and signaling were measured by 3D spheroid growth, ELISA, Western, and mouse xenograft experiments. Results: In vitro studies show that IGF-1 and HRG are potent activators of AKT signaling, leading to increased pancreatic tumor cell proliferation and decreased sensitivity to gemcitabine and nab-paclitaxel. MM-141 inhibits ligand-induced AKT activation, induces IGF-1R and ErbB3 degradation better than a mixture of IGF-1R and ErbB3 antibodies, and sensitizes cells to gemcitabine and nab-paclitaxel, in vitro. In vivo, MM-141 combines favorably with a nab-paclitaxel/gemcitabine regimen, leading to curative outcomes in a subset of treated mice. Conclusions: ErbB3 and IGF-1R co-inhibition is required to inhibit AKT signaling in pancreatic adenocarcinoma cell lines. These receptors are associated with chemoresistance to gemcitabine and nab-paclitaxel, which is abrogated by co-administration with MM-141. MM-141-induced degradation of oncogenic receptor complexes is likely essential to reverse chemoresistance and enhance effects of the nab-paclitaxel/gemcitabine regimen. These data, taken together with wide-spread expression of IGF-1R and ErbB3 in Stage IV pancreatic adenocarcinoma tissue, support clinical exploration of a MM-141/nab-paclitaxel/gemcitabine regimen in frontline metastatic pancreatic cancer. Preparations for a randomized Phase 2 study are underway.
Poor ambulance response causes 700 deaths annually in Ireland
Authors: Doug Payne
Journal: BMJ (2000)

Up to 700 people die in the Republic of Ireland each year because of the slow response times of ambulances in rural areas, according to research by the country's Association of Ambulance Personnel. The association has said that the patchy service is the result of health authorities trying to save money. It has compiled figures showing that at night time it takes an average of 20 …
Treatment of human immunodeficiency virus-related lymphoma with risk-adapted intensive chemotherapy: Final analysis of the NHL-HIV 93 trial
Authors: N. Mounier, M. Spina, J. Gabarre, M. Raphael, A. Carbone, J.-B. Golfier, A. Bosly, B. Coiffier, E. Vaccher, U. Tirelli, C. Gisselbrecht
Journal: Journal of Clinical Oncology (2005)

6524 Background: Treatment of AIDS-related lymphoma (ARL) is still controversial, as intensive chemotherapy could exacerbate immunodeficiency, with subsequent adverse effects for patients. We aimed to compare the effectiveness of risk-adapted intensive chemotherapy in patients with ARL treated in the NHL-HIV 93 randomized trial, before and after the use of highly active antiretroviral therapy (HAART). Methods: 485 patients aged from 18 to 67 years were randomly assigned to CHOP based chemotherapy with a pretreatment stratification of the dose-intensity according to the HIV score which is based on performance status, prior AIDS and CD4+ cell counts <0.1 G/l. Chemotherapy was administered in conjunction with HAART for the 187 patients enrolled after June 1996. Three main histologic types of ARL were represented in the study population: diffuse large cell lymphoma (54%), Burkitt lymphoma (20%) and immunoblastic lymphoma (17%). Results: With 6 years median follow-up, the OS was estimated, in the low risk group (HIV score=0, n=218), at 51% for high-dose CHOP (ACVBP) versus 47% for CHOP (p=0.85). In the intermediate risk group (HIV score=1, n=177), it was 28% for CHOP versus 24% for ld-CHOP (p=0.19) and in the high risk group (HIV score=2–3, n=90), 11% for ld-CHOP versus 3% for VS (vincristine, steroid) (p=0.14). CR rate of CHOP was significantly different of the ld-CHOP (49% vs. 32%, p=0.02) but not of the ACVBP (51% vs. 61%, p=0.17). Patients in the post HAART area had higher CD4 + counts, lower HIV score and less Burkittts subtype than patients in the pre-HAART area. After adjusting for the follow up, OS was higher in the post HAART area (21% vs. 37% at 3 yrs, p<0.001) but there was no difference between the therapeutic effects of the chemotherapy arm in each risk group. Time dependent Cox model demonstrated that the only significant factors were HAART (RR 1.6, p=0.0002), HIV score (RR 1.7, p=0.0001) and IPI score (RR 1.5, p=0.0012). Conclusions: Our findings indicate that benefit of ACVBP in ARL is not significant over the standard CHOP chemotherapy even in the post HAART area. On the other hand, ld-CHOP is not an alternative for CHOP because it led to lower CR rate and poor survival. No significant financial relationships to disclose.
Reducing non-attendance at outpatient clinics
Authors: Christopher A Stone, John H Palmer, Peter J Saxby, Vikram S Devaraj
Journal: Journal of the Royal Society of Medicine (1999)

Outpatient non-attendance is a common source of inefficiency in a health service, wasting time and resources and potentially lengthening waiting lists. A prospective audit of plastic surgery outpatient clinics was conducted during the six months from January to June 1997, to determine the clinical and demographic profile of non-attenders. Of 6095 appointments 16% were not kept. Using the demographic information, we changed our follow-up guidelines to reflect risk factors for multiple non-attendances, and a self-referral clinic was introduced to replace routine follow-up for high risk non-attenders. After these changes, a second audit in the same six months of 1998 revealed a non-attendance rate of 11%--i.e. 30% lower than before. Many follow-up appointments are sent inappropriately to patients who do not want further attention. This study, indicating how risk factor analysis can identify a group of patients who are unlikely to attend again after one missed appointment, may be a useful model for the reduction of outpatient non-attendance in other specialties.
Myelofibrosis With Myeloid Metaplasia: Diagnostic Definition and Prognostic Classification for Clinical Studies and Treatment Guidelines
Authors: Giovanni Barosi
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder characterized by bone marrow fibrosis and extramedullary hematopoiesis. Recent studies provide definite diagnostic criteria and prognostic classifications of the disease, and allogeneic stem-cell transplantation (SCT) now offers a chance of curing the disease. In order to put diagnostic criteria and prognostic classifications of the disease into the perspective of developing guidelines for treatment strategies, all studies published in the English literature over the last 30 years were reviewed. MATERIALS AND METHODS: Studies were identified through a MEDLINE search (1966 to present) and from the bibliographies of relevant articles. RESULTS: The Italian Consensus Conference on diagnostic criteria is a structured enterprise aimed at formulating a definition of MMM that will be used for enrolling patients onto clinical studies. It relies on the obligatory presence of myelofibrosis and on the exclusion of the BCR-ABL rearrangement or Philadelphia chromosome, in association with combinations of traditional features. Prognostic scores allow us to identify classes of patients on the basis of hemoglobin, age, WBC count, and chromosomal abnormalities. Several nonrandomized studies have indicated that allogeneic SCT for patients under the age of 55 is effective in prolonging survival in more than 50% of cases and in possibly curing the disease. Patients with the most severe prognosis are candidates. CONCLUSION: “Consensus” methodology offers a definition of MMM useful for conducting and reporting clinical studies. A detailed knowledge of prognostic factors can help to delineate guidelines for addressing patients with allogeneic SCT.
Measuring Asthma Control
Authors: ELIZABETH F. JUNIPER, PAUL M. O'BYRNE, PENELOPE J. FERRIE, DEREK R. KING, JEREMY N. ROBERTS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Daily symptom, peak expiratory flow rate (PEFR), and medication diaries are often used in clinical trials of treatments for asthma on the assumption that they provide a better estimate of clinical status than does a questionnaire completed in the clinic. We conducted a study with the aim of comparing the measurement properties of the clinic-completed Asthma Control Questionnaire with those of the Asthma Control Diary. The diary is composed of questions and response options almost identical to those of the questionnaire, but uses PEFR instead of FEV(1) as the measure of airway caliber. In an observational study, 50 adults with symptomatic asthma attended a McMaster University asthma clinic at 0, 1, 5, and 9 wk to complete the Asthma Control Questionnaire and other measures of asthma status. For 1 wk before each follow-up visit, patients completed the Asthma Control Diary every morning and evening. Concordance between the questionnaire and diary was high (intraclass correlation coefficient [ICC] = 0.87). Both reliability (ICC: questionnaire = 0.90; diary = 0.86) and responsiveness (responsiveness index: questionnaire = 1.06; diary = 0.90; p = 0.005) were better with the questionnaire than with the diary. Correlations between the two instruments and other measures of clinical asthma status were similar and close to a priori predictions. Both the Asthma Control Questionnaire and the Asthma Control Diary are valid instruments for measuring asthma control, but the questionnaire has slightly better discriminative and evaluative measurement properties than does the diary.
Cognitive Motor Dissociation Following Severe Brain Injuries
Authors: Nicholas D. Schiff
Journal: JAMA Neurology (2015)

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