tbuckley/cabot-search huggingface dataset:
Striking Regression of Chronic Radiotherapy Damage in a Clinical Trial of Combined Pentoxifylline and Tocopherol
Authors: Sylvie Delanian, Saida Balla-Mekias, Jean-Louis Lefaix
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Radiation-induced fibrosis (RIF) remains the most morbid complication of radiotherapy because of the absence of spontaneous regression and the difficulty of patient management. RIF treatment with combined pentoxifylline (PTX) and tocopherol (Vit E) was prompted by recent advances in cellular and molecular biology that have improved researchers' understanding of radiation-induced late-injury mechanisms and by the excellent results from our previous human and animal studies. PATIENTS AND METHODS: Forty-three patients (mean [± SD] age, 59 ± 10 years) presenting with 50 symptomatic RIF areas involving the skin and underlying tissues were treated from April 1995 to September 1997. Patients had had radiotherapy for head and neck or breast cancer a mean period of 8.5 ± 6.5 years previously. RIF developed in the first year after irradiation and gradually worsened, without spontaneous regression. The mean measurable surface area of RIF ([S]) at the time of this study ([S 0 ]) was 42 ± 34 cm 2 . The initial Subjective Objective Medical management and Analytic (SOMA) injury evaluation score was 13.2 ± 5.9 and included evidence of edema, plexitis, restricted movement, and local inflammatory signs. A combination of PTX (800 mg/d) and Vit E (1,000 IU/d) was administered orally for at least 6 months. RESULTS: Treatment was well tolerated. All assessable injuries exhibited continuous clinical regression and functional improvement. Mean RIF surface area and SOMA scores improved significantly (P &lt; .0001) at 3 months ([S 3 ], −39%; [SOMA 3 ], −22%), 6 months ([S 6 ], −53%; [SOMA 6 ], −35%), and 12 months ([S 12 ], −66%; [SOMA 12 ], −48%), and mean linear dimensions ([D]) diminished from the start of the study ([D 0 ], 6.5 ± 2.5 cm) to the end of treatment 12 months later ([D 12 ], 4 ± 2 cm). At the time of the treatment, we did not attempt to achieve the maximum effect, and the study was continued. CONCLUSION: The PTX-Vit E combination reversed human chronic radiotherapy damage and, because no other treatment is presently available for RIF, should be considered as a therapeutic measure.
Diffuse idiopathic pulmonary endocrine cell hyperplasia (DIPNECH) requiring bilateral sequential lung transplant
Authors: Matthew Howard Jones, Deborah Wales, Richard Thompson, Desley Neil
Journal: European Respiratory Journal (2013)

Introduction:  DIPNECH is a rare disorder with only around 50 cases published. It is characterised by abnormal proliferation of neuroendocrine cells along respiratory epithelium.   Case Study:  A sixty-three year old lady, an ex-smoker, underwent bilateral sequential lung transplant for presumed emphysema in November 2011. She was first referred to a Respiratory Physician in 1993 with persistent cough and dyspnoea and occasional hamoptysis. An initial diagnosis of asthma was made, later replaced by COPD. Her breathlessness increased with severe disability. She commenced oxygen therapy in 1997 and she developed type 2 respiratory failure in 2000. Disabling breathlessness prompted referral for lung transplantation in 2008. Histology of the explanted lungs showed DIPNECH.   Discussion:  DIPNECH occurs predominantly in non-smoking, middle-aged women. Presenting symptoms include cough and dyspnoea. Diagnosis is often delayed. A lack of diagnostic radiological features makes tissue biospy the gold standard for diagnosis. Outcomes in a previous Systematic Overview were variable with many patients achieving clinical stability or improvement¹. Our case was characterised by a progressive decline in lung function and respiratory failure.   Conclusion:  We present the first confirmed case study in medical literature of a patient undergoing bilateral lung transplantation for DIPNECH.   References:  1. Nassar A. Jarpszewslo E. et al.Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia. A systematic Overview. Am J Respir Crit Care Med 2011 Vol 184. pp8-16.
Updated safety and survival of patients with relapsed glioblastoma treated with bevacizumab in the BRAIN study.
Authors: T. Cloughesy, J. J. Vredenburgh, B. Day, A. Das, H. S. Friedman
Journal: Journal of Clinical Oncology (2010)

2008 Background: Patients (pts) with relapsed glioblastoma (GBM) suffer considerable morbidity and mortality. We analyzed updated safety and survival data from the BRAIN trial of bevacizumab (BV) alone or in combination with irinotecan (IR). Methods: Results of BRAIN, a phase II, open-label, multicenter, randomized, noncomparative trial of GBM at first or second relapse, during the planned treatment period (PTP) with BV (n=85) and BV+IR (nn=8582), have been reported (J Clin Oncol 27:4733-4740, 2009). BV-arm pts with progression who met eligibility criteria could enroll in a postprogression phase (PP) to receive BV+IR. Survival was defined from randomization to death from any cause. Pts lost to follow-up were censored at the date they were last known to be alive. Median overall survival (OS) with 95% CIs and 12-,18-, 24-, and 30-month (mo) Kaplan-Meier survival rates were calculated. Adverse events (AEs) were graded according to NCI criteria (v 3.0). Results: Median OS at last follow-up (15 July 2009) was 9.3 mo (95% CI 8.2–11.8) in the BV arm and 8.9 mo (95% CI 7.9–11.9) in the BV+IR arm. Updated safety data (15 July 2008) for 163 pts who received study drug are shown (Table). The median number of BV doses received during PTP was 9 and 11 for BV and BV+IR and 3 during PP. Conclusions: Updated survival data from BRAIN showed that up to 16% of pts remained alive at 30 mo. The incidence of selected AEs in the updated safety data was consistent with that previously reported, and no new safety signals were identified. BV (n=85) BV+IR (n=82) Survival rate from randomization to death, % 12 mo 38 38 18 mo 24 18 24 mo 16 17 30 mo 11 16 BV (n=84) BV+IR (n=79) PP (BV+IR) (n=50) Safety, n (%) All AEs (any grade; grade ≥3) 83 (98.8); 43 (51.2) 79 (100); 56 (70.9) 49 (98); 26 (52.0) Selected AEs (any grade; grade ≥3) Hypertension 33 (39.3); 9 (10.7) 23 (29.1); 3 (3.8) 2 (4); 0 Cerebral hemorrhage 3 (3.6); 0 3 (3.8); 1 (1.3) 3 (6); 0 Venous thromboembolism 3 (3.6); 3 (3.6) 9 (11.4); 8 (10.1) 3 (6); 3 (6) Proteinuria 6 (7.1); 1 (1.2) 5 (6.3); 3 (3.8) 1 (2); 1 (2) Wound healing complications 5 (6.0); 2 (2.4) 2 (2.5); 1 (1.3) 3 (6); 1 (2) Arterial thromboembolism 4 (4.8); 3 (3.6) 3 (3.8); 2 (2.5) 1 (2); 1 (2) GI perforation 0 2 (2.5); 2 (2.5) 1 (2); 1 (2) RPLS 0 1 (1.3); 0 0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Roche Genentech Genentech Genentech
Agent Orange Exposure and Monoclonal Gammopathy of Undetermined Significance
Authors: Ola Landgren, Youn K. Shim, Joel Michalek, Rene Costello, Debra Burton, Norma Ketchum, Katherine R. Calvo, Neil Caporaso, Elizabeth Raveche, Dan Middleton, Gerald Marti, Robert F. Vogt
Journal: JAMA Oncology (2015)

Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans.To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans.This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS.Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002.Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs.The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P=.007).Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.
Association Between Catechol <b><i>O</i></b>-Methyltransferase Genotype and Violence in Schizophrenia and Schizoaffective Disorder
Authors: Herbert M. Lachman, Karen A. Nolan, Pavel Mohr, Takuya Saito, Jan Volavka
Journal: American Journal of Psychiatry (1998)

The authors previously reported a relationship between an allele encoding the low activity variant of catechol O-methyltransferase (COMT) and aggressive behavior in schizophrenic patients. This study replicates and extends these findings by using more direct measures of violent behavior.Fifty-five white patients (34 men, 21 women) with DSM-IV diagnoses of schizophrenia or schizoaffective disorder were selected to form two groups (violent and nonviolent) on the basis of history of aggressive behavior. COMT genotypes were determined by restriction fragment length polymorphism analysis.A significant association was found between COMT genotype and history of violent behavior. Sixty-four percent of patients homozygous for the low-activity COMT allele were violent; 80% of patients homozygous for the high-activity allele were nonviolent.The gene determining the activity of an important regulatory enzyme in catecholamine inactivation is associated with violent behavior in patients with schizophrenia and schizoaffective disorder.
Three immediately applicable treatments: manual therapy, avoiding cortisone, and automatic external defibrillators
Authors: Karim Khan
Journal: British Journal of Sports Medicine (2008)

Are you interested in neck and back pain or injury prevention? Have you injected cortisone? Do you think you might eventually die? If you answered “yes” to any of these questions this Warm up is for you. Recent world conferences for a broad range of clinicians provided many highlights.

For those who needed more proof of the effectiveness of manual therapy, and sadly there are some physicians who do, I share a key finding from the 9th International Congress of the International Federation of Orthopaedic Manual Therapists (IFOMT). A systematic review of manual therapy in neck or back pain concluded that the treatment was effective with a “number needed to treat” of only five. Thus, manual therapy was about 100 times as effective when used to combat neck or back pain as osteoporosis drugs are to prevent hip fractures.1 If five patients are treated with …
SHOCK THERAPY IN PSYCHOSES DURING PREGNANCY
Authors: CARROL C. TURNER, LEONARD D. WRIGHT
Journal: American Journal of Psychiatry (1947)

One psychotic pregnant female was treated by electroshock therapy between the fourth and sixth months of pregnancy, without the use of supplementary medication. A total of 17 treatments, with major convulsions, was given. This patient went into labor at the normal time, and a normal baby girl was delivered by Caesarian section. At this time procedures for sterilization were carried out, at the request of her husband. Follow-up in this case reveals a normal, healthy infant and a mother who has, apparently, fully recovered.
What are the Psychological Factors Influencing Attendance, Non-Attendance and Re-Attendance at a Breast Screening Centre?
Authors: L J Fallowfield, A Rodway, M Baum
Journal: Journal of the Royal Society of Medicine (1990)

We describe some preliminary findings from a pilot study using three recently developed questionnaires which assessed items such as the health beliefs, knowledge about cancer and attitudes to breast cancer screening in 242 women invited to attend for mammographic screening in South East London. We suggest that these questionnaires should be used in all regional centres both to monitor psychological variables and to identify local problems within the service which may be influencing the up-take of invitations to come for screening.
Ready, steady, go (RSG): Addressing the needs of adolescents in transition from child to adult services
Authors: Amanda Harris, Judi Maddison, Tricia McGinnity, Jane Lucas, Arvind Nagra
Journal: European Respiratory Journal (2014)

Studies show effective transition between child & adult care improves long term outcomes. RSG is a generic programme designed & implemented to address the challenges transition presents. Medical, psychosocial & vocational needs of individuals are addressed following a structured yet adaptable plan, supported by Young Persons Clinic weeks. RSG addresses issues common to all young people but allows the respiratory team to focus on individual9s specific needs. It commences at 11years coinciding with transition to senior school. A key principle of the programme is to empower young perople to take control of their lifes & equip them with the necessary skills to function independently & confidently in the adult services   Objectives   To assess the effectiveness of RSG   Method   Questionnaires were designed to assess the effectiveness of the RSG documentation looking at whether it  -Is simple to understand  -Is easy to use  -Aids transition process  -Improves clinical practice   Results   93 completed questionnaires  -40 patients  -31 parents  -22 professionals   Conclusions   RSG is an effective tool for delivering optimal transition to adult services.
P99 Relation of donor risk index and model for end-stage liver disease score to outcome of elective liver transplantation; a single centre experience
Authors: M Al-Freah, M A B Al-Freah, E Dionigi, A Suddle, V Aluvihare, K Agarwal, J Wendon, G Auzinger, J O'Grady, M Rela, M Heneghan, N Heaton, W Bernal
Journal: Gut (2010)

Introduction  Patients with advanced liver disease, reflected in high model for end-stage liver disease (MELD) scores have the lowest chances of survival without liver transplantation (LT) and yet, may derive greatest survival-benefit from LT. The use of extended criteria (EC) grafts in such patients has been advocated as a means of optimising the chances of successful transplantation.  Aim  To determine the effects of graft quality (using Donor Risk Index, DRI) and MELD score at the time of LT on the duration of post-LT intensive care unit (ICU) and hospital length of stay (LOS) and survival.  Method  Retrospective analysis of 898 adult patients who underwent elective LT (109 re-do LT) over the period 2000–2008. Pre-LT MELD scores were categorised as low ( 25). Graft quality was categorised as low (DRI >1.7) or High (DRI   Results  Median age was 53 years (44–60) and 64% were male. Median pre-LT MELD was 15 (11–19) and median DRI in the high and low quality groups were 1.5 (1.3–1.6) and 2.0 (1.9–2.1). Increasing MELD score was associated with greater ICU and Hospital LOS (p 1.7. See Abstract P99 table 1.  On multivariate regression analysis MELD was an independent predictor of LOS with no significant effect of DRI identified. Survival at 1-year in the overall cohort was 90%; in MELD  25 82.7%. There were no significant differences in 1 year survival between recipients with DRI  1.7 in the group as a whole or in the MELD sub-categories.  Conclusion  In this cohort, length of ICU and hospital stay related to pre-LT MELD score and not graft quality as evaluated by DRI. Hospital and ICU stay and consequently resource use was increased particularly in those patients with MELD of 25 and above, but not further prolonged by the use of ECD grafts in the range of DRI used in this cohort.
Recruiting to telehealth has a role during discharge planning in COPD: A feasibility and acceptability study
Authors: Claire Lawless, Doytchin Dimov
Journal: European Respiratory Journal (2013)

Introduction:Current UK guidance encourages out of hospital management of COPD. Telemetric monitoring systems may aid this by allowing remote monitoring, education, and support. There has been relatively slow uptake of the technology within secondary care. This study aims to ascertain the feasibility and acceptability of recruiting COPD patients to this service as part of the discharge planning process.  Methods:Eligibility for telehealth was assessed in all patients admitted with an exacerbation of COPD over 1 month using predetermined criteria. Patients were approached by a doctor to check if they were prepared to accept the service. A nurse contacted them after discharge to set it up.  Results:69 patients assessed for eligibility. 48 fitted the criteria and were approached. 22 male. Mean age 68 (49-84).  26 (54.1%) patients gave their consent to receive further information. Of the remaining, 6 (12.5%) already had a telehealth device, 4 (8.3%) were on the waiting list, 8 (16.6%) did not have a landline, 4 (8.3%) did not wish to have telehealth. Of those not wishing to have telehealth, 3 did not like the idea, 1 said he “didn’t want to rely on a machine”.  Conclusions: 69.6% of patients admitted were eligible. 75% of those eligible either agreed to be given the device or were already using it/on the waiting list. Not having a telephone landline at home was the biggest single barrier to being recruited. A small proportion of those approached were opposed to the idea. This data confirms that recruitment to telehealth as part of the discharge planning process in COPD is both feasible and acceptable. This information will be useful for the future service planning.
Natural Course of Neuroblastoma Detected by Mass Screening: A 5-Year Prospective Study at a Single Institution
Authors: Hirokazu Nishihira, Yasunori Toyoda, Yukichi Tanaka, Rieko Ijiri, Noriko Aida, Maho Takeuchi, Kei Ohnuma, Hisato Kigasawa, Keisuke Kato, Toshiji Nishi
Journal: Journal of Clinical Oncology (2000)

To describe various favorable courses of neuroblastoma (NBL) detected by mass screening and to present our observation program as a temporary treatment option, to be used until a final decision is made regarding the mass screening program for 6-month-old infants.Between October 1993 and November 1999, 26 of 51 patients with NBL detected by mass screening were enrolled in our observation program. The criteria for observation included urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels less than 50 microg/mg creatinine, smaller tumor size (< 5.0 cm), preoperative status, and granted informed consent. Patients were divided into four groups according to changes in urinary VMA and HVA values and tumor size. Patients who no longer fulfilled criteria underwent surgery.The observation period ranged from 4 to 73 months. Urinary VMA and HVA levels decreased in 19 of 26 patients, often by age 16 months. Eighteen patients had regressing tumors, and in 10 of these cases, the tumor was undetectable or barely detectable by imaging techniques. Four patients younger than 12 months had increased tumor marker levels and tumor volume, histologically reflecting neuroblastic proliferation. The remaining three patients, all older than 18 months, had varied tumor marker levels but increased tumor volume, histologically reflecting an increase in Schwann cells. No upgrading of tumor stage or unfavorable biologic factor was noted in any patient.None of our patients showed evidence of transition from favorable to unfavorable prognosis, a finding that points to a reduction in the significance of screening as a public health measure. Until results of ongoing screening trials involving older patients have been evaluated, the observation program can be used as a temporary measure to avoid, with little risk, unnecessary surgical intervention.
Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity
Authors: Paul R. Giacomin, Ryan H. Moy, Mario Noti, Lisa C. Osborne, Mark C. Siracusa, Theresa Alenghat, Bigang Liu, Kelly A. McCorkell, Amy E. Troy, Gregory D. Rak, Yinling Hu, Michael J. May, Hak-Ling Ma, Lynette A. Fouser, Gregory F. Sonnenberg, David Artis
Journal: The Journal of Experimental Medicine (2015)

Innate lymphoid cells (ILCs) are critical for maintaining epithelial barrier integrity at mucosal surfaces; however, the tissue-specific factors that regulate ILC responses remain poorly characterized. Using mice with intestinal epithelial cell (IEC)-specific deletions in either inhibitor of κB kinase (IKK)α or IKKβ, two critical regulators of NFκB activation, we demonstrate that IEC-intrinsic IKKα expression selectively regulates group 3 ILC (ILC3)-dependent antibacterial immunity in the intestine. Although IKKβ(ΔIEC) mice efficiently controlled Citrobacter rodentium infection, IKKα(ΔIEC) mice exhibited severe intestinal inflammation, increased bacterial dissemination to peripheral organs, and increased host mortality. Consistent with weakened innate immunity to C. rodentium, IKKα(ΔIEC) mice displayed impaired IL-22 production by RORγt(+) ILC3s, and therapeutic delivery of rIL-22 or transfer of sort-purified IL-22-competent ILCs from control mice could protect IKKα(ΔIEC) mice from C. rodentium-induced morbidity. Defective ILC3 responses in IKKα(ΔIEC) mice were associated with overproduction of thymic stromal lymphopoietin (TSLP) by IECs, which negatively regulated IL-22 production by ILC3s and impaired innate immunity to C. rodentium. IEC-intrinsic IKKα expression was similarly critical for regulation of intestinal inflammation after chemically induced intestinal damage and colitis. Collectively, these data identify a previously unrecognized role for epithelial cell-intrinsic IKKα expression and TSLP in regulating ILC3 responses required to maintain intestinal barrier immunity.
Risk factors and clinical outcomes of candidaemia in patients treated for Clostridium difficile infection
Authors: A. Russo, M. Falcone, M. Fantoni, R. Murri, L. Masucci, P. Carfagna, M.C. Ghezzi, B. Posteraro, M. Sanguinetti, M. Venditti
Journal: Clinical Microbiology and Infection (2015)