tbuckley/cabot-search huggingface dataset:
Management of adult acute lymphocytic leukemia: present issues and key challenges.
Authors: A Preti, H M Kantarjian
Journal: Journal of Clinical Oncology (1994)

PURPOSE To discuss the controversies in current adult acute lymphocytic leukemia (ALL) management in relation to its different phases of therapy. DESIGN A review of treatments in adult ALL from the English literature. RESULTS Features signaling high risk for systemic relapse (older age, high WBC count at diagnosis, non-T-cell immunophenotype, Philadelphia chromosome (Ph)-positive karyotype, and longer time to achieve remission) are found in 60% to 70% of patients with adult ALL. These patients have a potential cure rate of 20% to 25%, compared with 60% to 70% for low-risk patients. Induction regimens with vincristine, anthracyclines, and corticosteroids appear to be optimal. Intensification-consolidation therapy increased cure rates modestly in adult ALL; higher-dose schedules of mercaptopurine (6-MP), methotrexate, and asparaginase may be beneficial. Maintenance therapy with 6-MP and methotrexate is suggested based on the worse outcome of patients in whom such maintenance was omitted. Allogeneic bone marrow transplantation (BMT) is indicated for patients in first remission with high-risk for relapse; autologous BMT for patients in first remission remains investigational. Patients with mature B-cell ALL require short-term, dose-intensive therapy that alternates hyperfractionated doses of cyclophosphamide with high-dose cytarabine (ara-C) and methotrexate. Patients with T-cell ALL may benefit from ara-C/cyclophosphamide combinations during maintenance therapy. CNS prophylaxis with intrathecal chemotherapy should be administered in patients at risk for CNS relapse. CONCLUSION Potential strategies to improve the prognosis of high-risk patients with ALL include increasing the dose-intensity of remission induction and consolidation-intensification therapies with growth factor support; discovering and using new anti-ALL drugs; improving autologous BMT results; translating biologic studies of leukemia cell characteristics, karyotype-related molecular aberrations, abnormal oncogenic expression, and minimal residual disease into clinically relevant therapies; and using investigational treatment strategies in high-risk patients.
Cardiac function in Wilms' tumor survivors.
Authors: K Sorensen, G Levitt, D Sebag-Montefiore, C Bull, I Sullivan
Journal: Journal of Clinical Oncology (1995)

PURPOSE To study late cardiac function in a single diagnostic group (children with Wilms' tumor) with good long-term survival; to compare patients treated with anthracyclines (doxorubicin) with patients treated without anthracyclines and with a normal child/adolescent group; and to examine the risk factors involved in late cardiac dysfunction. PATIENTS AND METHODS Echocardiographic studies were performed on 97 Wilms' tumor patients treated with anthracyclines (mean cumulative dose, 303 mg/m2) with a mean follow-up time of 7.1 years, on 39 Wilms' tumor patients treated without anthracyclines with a mean follow-up time of 8.9 years, and on 50 normal subjects. Left ventricular (LV) dimensions, end systolic wall stress (a measure of afterload), and load-dependent and -independent measures of contractility were compared between groups. Potential risk factors, including age at diagnosis, follow-up duration, sex, pubertal status, cardiac irradiation, dose-intensity, and cumulative dose of anthracyclines, were studied by multivariate analysis. RESULTS Twenty-five percent of the anthracycline-treated group showed cardiac abnormalities. All but one of these patients had increased LV afterload. Risk factors for increased afterload were anthracycline cumulative dose (P &lt; .05) and anthracycline dose-intensity (P &lt; .02). Wilms' tumor patients treated without anthracyclines had thickened LV walls compared with normal subjects (P &lt; .05). CONCLUSION Total dose and dose-intensity of anthracycline were risk factors for increased LV afterload in long-term Wilms' tumor survivors treated on standard protocols. The increase in afterload accounted for reduced LV shortening, whereas contractility was rarely abnormal. The new finding that Wilms' tumor survivors who do not receive anthracyclines have mild LV hypertrophy may provide some protection against anthracycline-induced cardiotoxic effects.
Particular aspects of TB endemia in Bucharest after adoption DOTS strategy
Authors: Emilia Tabacu, Elmira Ibraim, Cristian Didilescu
Journal: European Respiratory Journal (2012)

Bucharest, Romania's capital, a great urban agglomeration with almost 2 000 000 inhabitants and a population density of 8 528 inhabitants/Km², was confronted with a rate, sometimes wery high of tuberculosis cases for a long time period. Objective: The study of the main indicators of the TB endemic in Bucharest between years 2001 - 2011. Material and method: We used the information existing in the official documents of the information system within the National Program of Tuberculosis Control. Results: In 1963 the tuberculosis incidence reached 223%ooo inhabitants, after presenting a clear tendency of reduction till 1985 (65,9%ooo). After last year, an appreciable increase of the tuberculosis incidence installed, reaching 154,1%ooo in 2001, after which a decrease occurred yearly, reaching 67,5%ooo in 2011. The incidence for new cases decrease from 135,8%ooo in 2001 to 56,9%ooo in 2011 and the incidence for relapses decrease from 18,3%ooo in 2001 to 10,7%ooo in 2011. The tuberculosis incidence in the 0-14 year children population decrease from 60,8%ooo in 2001 to 21,4%ooo in 2011. The source density was reduced from 12 sources/Km2 in 2001 to 5 sources/Km2 in 2011. DOTS strategy implemented in Bucharest proved to be an important weapon for TB control, success rate increase yearly. The rate of the therapeutic success of the new source cases with pulmonary TB (M+) increased from 82,2% in the patient cohort from 2001 to 86% in those from 2009. Conclusion: The strict monitoring of the treatment is the medical key in fighting the tuberculosis.
Endocrine complications in children treated for medulloblastoma or ependymoma using radiation therapy. Outcomes in the CT-planning era
Authors: G. Bahl, S. Urbach, U. Bartels, D. C. Hodgson, B. Millar, A. Parent, L. Le, S. Awrey, N. Laperriere
Journal: Journal of Clinical Oncology (2009)

10064 Background: The purpose of this study is to determine the frequency of late endocrine complications following radiation therapy (RT) in children treated for medulloblastomas or ependymomas. Methods: Seventy children with medulloblastoma or ependymoma were treated using RT from June 2000 to June 2005 at our institute. Median age at diagnosis was 6 years (range 1–17), and 52 (74%) were boys. Forty-eight patients (69%) had medulloblastomas and 22 (31%) had ependymomas. Twenty-two received highly conformal RT to the tumor bed alone (focal RT: median dose 54 Gy, range 54–59.4), 24 received low dose cranio-spinal RT (CSI: median dose 23.4 Gy) followed by a boost to the post fossa/tumor bed (median 30.6 Gy), and 24 patients received high dose CSI (median 36 Gy) followed by a boost (median 18 Gy). Only two of the 22 children with ependymomas received CSI. All patients underwent CT-based planning and were treated using conventional fractionation; 58 (83%) also received chemotherapy. None of the children had documented endocrinopathy prior to diagnosis. Results: After a median follow-up of 65.3 months, the 5-yr PFS and OS was 70% and 75% for children with medulloblastomas, and 54% and 84% for patients with ependymomas, respectively. Thirty-five children developed evidence of endocrinopathy (Growth hormone deficiency (GHD): 31, hypothyroidism (HPT): 23, precocious puberty (PP): 6, gonadotropin deficiency: 3, ACTH deficiency: 2, and diabetes insipidus: 2). The 5-yr cumulative incidence (CI) of endocrinopathy was 71% for the children treated with CSI vs. 18% for those treated with focal RT (Gray's test p-value = 0.004). The median time to development of endocrinopathy was 38 months for the patients who had CSI. For these children the 5-yr CI was 68% for GHD, 52% for HPT, and 16% for PP. There was no significant difference in the incidence of endocrinopathy for patients treated with low dose vs. high dose CSI. Conclusions: The 5-yr CI of endocrine toxicity in children treated with cranio-spinal RT is 71% (median time to development: 38 months), which is significantly higher than in children treated with focal RT. All children treated for medulloblastomas or ependymomas require long-term surveillance and close monitoring for the development of endocrinopathies. No significant financial relationships to disclose.
Radiation therapy versus combination chemotherapy in the treatment of early-stage Hodgkin's disease: seven-year results of a prospective randomized trial.
Authors: D L Longo, E Glatstein, P L Duffey, R C Young, S M Hubbard, W J Urba, M N Wesley, A Raubitschek, E S Jaffe, P H Wiernik
Journal: Journal of Clinical Oncology (1991)

The study population included 136 patients with stage IA, IB, IIA, IIB, or IIIA1 Hodgkin's disease. The median follow-up is 7.5 years. Among the 30 patients with peripheral IA disease, all patients achieved a complete response (CR) with radiation therapy, and no patient has relapsed. Patients of other stages were randomized to receive radiation therapy or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Among the 51 patients randomized to receive radiation therapy, 49 (96%) achieved complete remission, 17 (35%) have relapsed, and 10 (20%) have died. Fifty-two of the 54 (96%) assessable patients randomized to receive MOPP obtained CRs, seven (13%) have relapsed, and four (7%) have died. The projected 10-year disease-free survival of patients randomized to receive radiation therapy is 60%; for those randomized to receive MOPP, it is 86% (P2 = .009 in favor of MOPP). The projected 10-year overall survival for patients randomized to radiation therapy is 76%, and for MOPP-treated patients it is 92% (P2 = .051 in favor of MOPP). When the randomized patients with massive mediastinal disease or stage IIIA1 disease were excluded from the analysis, the disease-free (67% for radiation v 82% for MOPP) and overall survival (85% for radiation v 90% for MOPP) were not significantly different between the two arms. Subset analysis showed significant superiority of MOPP in the treatment of the following patient groups: stage IIIA1 or massive mediastinal disease, no B symptoms, initial erythrocyte sedimentation rate greater than 20 mm, four or more sites of disease, and younger than age 40 years. Preliminary analysis of this ongoing study shows that MOPP chemotherapy is at least as effective as radiation therapy in the treatment of the specific groups of early-stage Hodgkin's disease patients randomized. The final assessment of these two diverse treatment options will depend largely on the long-term survival and the incidence of early- and late-treatment complications for which patients are continuing to be observed.
Metoclopramide: dose-related toxicity and preliminary antiemetic studies in children receiving cancer chemotherapy.
Authors: J C Allen, R Gralla, L Reilly, M Kellick, C Young
Journal: Journal of Clinical Oncology (1985)

Prior studies in adults have shown that metoclopramide (MCP), when given in high intravenous (IV) doses (2 mg/kg), is a highly effective antiemetic for chemotherapy-induced vomiting. It is well-tolerated in older adults, but younger adults have an increased disposition to acute extrapyramidal reactions (EPRs). Before studying the efficacy of MCP as an antiemetic in children, we first had to establish the safe dose range. We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin (120 mg/m2) or cyclophosphamide (greater than 900 mg/m2), beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg. MCP was given every two hours for four doses beginning one-half hour before chemotherapy. To reduce the incidence of EPRs, we added concomitant diphenhydramine. In MCP doses less than 2 mg, toxicity was minimal. In doses greater than or equal to 2 mg, 4/27 (15%) had EPRs and 9/27 (33%) had akathisia. Children who received two consecutive days of MCP had a higher frequency of EPRs. Metoclopramide (2 mg/kg) had promising antiemetic efficacy in a preliminary nonrandomized trial. Chemotherapy-experienced children vomited fewer than five times in 9/21 (43%) trials, and new patients vomited fewer than five times in 7/10 (70%) trials. MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed. Chemotherapy-induced emesis has the same negative implications in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting randomized clinical trials in children.
Effects of intrabrachial arterial infusion of pyruvate on forearm tissue metabolism
Authors: Thomas Pozefsky, Robert G. Tancredi
Journal: Journal of Clinical Investigation (1972)

Postabsorptive release of alanine from forearm skeletal muscle is large relative to other amino acids, suggesting new synthesis by transamination of pyruvate. This hypothesis was tested and the pathway quantified in six subjects, each given two 30 min intrabrachial arterial pyruvate infusions. The first (12 mumoles/min) supplied approximately that amount of pyruvate produced endogenously by glycolysis in resting muscle. The second (36 mumoles/min) approximated endogenous pyruvate production by glycolysis during moderate exercise. Changes in balance across forearm tissues of pyruvate, glucose, lactate, and amino acids were measured. The time-course of pyruvate equilibration across fore-arm muscles was detailed in three additional subjects. The two infusions increased arterial pyruvate from 64 to 674 and 1776 mumoles/liter respectively. Muscle consumed 72% of the exogenous pyruvate during both infusions. Outputs of lactate and alanine increased, accounting respectively for 30.3 and 6.7% of the pyruvate at the low infusion rate, and 17.1 and 3.8% at the high rate. The remaining pyruvate probably was oxidized. Muscle release of valine, isoleucine, and leucine decreased during the high dose infusion. Additionally, adipose tissue plus skin released more alanine and lactate during the high dose infusion. Other metabolies were unchanged.Thus, both muscle and adipose tissue plus skin synthesize alanine from pyruvate. Lactate production considerably exceeds that of alanine. In muscle, increased availability of intracellular pyruvate serving as a nitrogen acceptor may facilitate branched chain amino acid oxidation. Muscle consumption of infused pyruvate is rapid, and detailed studies of its equilibration suggest that passage across the muscle cell membrane is rate limiting.
Is nailfold videocapillaroscopy a valuable diagnostic tool in pulmonary hypertension
Authors: Florian Meier, Matthias Geyer, Henning Tiede, Andreas Rieth, Hossein Ardeschir Ghofrani, Ulf Müller-Ladner, Robert Dinser, Walter Hermann
Journal: European Respiratory Journal (2012)

Background:  Pulmonary hypertension (PH) can be based on idiopathic pulmonary arterial hypertension (iPAH), connective tissue diseases such as systemic sclerosis (SSc-PAH), left heart disease (LHD-PH), chronic obstructive pulmonary disease (COPD-PH), or chronic thromboembolic events (CTEPH).   Objectives:  Analysis of microvascular patterns of patients with PH has been performed using nailfold videocapillaroscopy (NVC). The benefit of NVC in PH was evaluated with focus on SSc patients.   Methods:  NVC was performed in 81 patients. 2nd-5th fingers were bilaterally analyzed. Pictures were scored for capillary density (CD, capillaries/mm), and dimensions. Parameters such as hemorrhages and neoangiogenesis or capillary alterations such as ectasia (>20µm) and giant shape (>50µm) were qualitatively assessed.   Results:  14.8% had iPAH, 14.8% LHD-PH, 7.4% COPD-PH and 17.2% CTEPH. 45.7% had SSc and 12.3% SSc-PAH. The CD in SSc-PAH was significantly lower compared to all other PH forms (4.9 vs. 10.2, 10.0, 11.7 and 9.47 in iPAH, LHD-PH, COPD-PH and CTEPH; p   Conclusions:  Assessing capillary density in PH is a powerful tool to discriminate between SSc-PAH and other forms of PH. In this respect, NVC should be considered, besides checking for antinuclear antibodies, if the underlying cause of PH is unclear to determine SSc-PAH.
Carcinoma-associated hemolytic-uremic syndrome: a complication of mitomycin C chemotherapy.
Authors: J E Cantrell, T M Phillips, P S Schein
Journal: Journal of Clinical Oncology (1985)

A thrombotic microangiopathy resembling the hemolytic uremic syndrome was diagnosed in 12 patients with adenocarcinoma, in whom the tumor was in complete or near-complete remission after treatment with mitomycin C-containing drug regimens. Microangiopathic hemolytic anemia, thrombocytopenia, and renal failure were initially present in all cases. All patients eventually developed pulmonary edema and systemic arterial hypertension, and three experienced neurologic complications. Blood transfusions exacerbated the syndrome in nine patients. High titers of platelet-aggregating plasma immune complexes were present in all six cases in which they were measured. The constituent antibody of each complex failed to react with mitomycin C antigen preparations, whereas in vitro reactivity to endodermally derived neoplasms was demonstrated. Plasmapheresis was associated with amelioration of the syndrome in only one patient. In patients receiving mitomycin C chemotherapy, the development of anemia and thrombocytopenia or azotemia may represent the initial manifestations of this newly defined thrombotic microangiopathy. A consistently effective form of management of this syndrome has not as yet been defined.
Obsessive-Compulsive Disorder Symptoms Before and After Recovery From Bulimia Nervosa
Authors: Kristin M. von Ranson, Walter H. Kaye, Theodore E. Weltzin, Radhika Rao, Hisato Matsunaga
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Obsessive-compulsive disorder (OCD) symptoms are common in people who are ill with bulimia nervosa. However, little is known about whether OCD symptoms persist after long-term recovery from bulimia. METHOD: Thirty-one female patients with bulimia nervosa, 29 women who had been recovered from bulimia for more than 1 year, and 19 healthy female comparison subjects completed the Yale-Brown Obsessive Compulsive Scale, which measures OCD-like symptoms. Items related to symptoms of core eating disorders were omitted from the Yale-Brown scale. RESULTS: The Yale-Brown scale scores of the women with bulimia (mean=13.1, SD=10.6) and those who had recovered from bulimia (mean=7.9, SD=7.0) were significantly higher than the scores of the normal comparison subjects (mean=1.9, SD=2.6). Women with bulimia and those who had recovered from bulimia had similar Yale-Brown scale scores and endorsed similar Yale-Brown scale target symptoms, such as obsessions related to symmetry and exactness. CONCLUSIONS: OCD symptoms persist after recovery from bulimia. Moreover, the types of OCD symptoms experienced by bulimia patients do not vary dramatically with improvement in bulimic symptoms. Persistent OCD symptoms after recovery from bulimia raise the possibility that these behaviors are trait-related and contribute to the pathogenesis of bulimia.
Thoracoabdominal contribution to tidal volume after an impatient cardiac rehabilitation program associated to continuous positive airway pressure
Authors: Camila B.F. Pantoni, Luciana Di Thommazo, Renata G. Mendes, Flávia C.R. Caruso, Daniel Mezzalira, Aparecida M. Catai, Othon Amaral Neto, Audrey Borghi-Silva
Journal: European Respiratory Journal (2012)

Background: Continuous positive airway pressure (CPAP) is an important strategy for improvement of gas exchange and breathing working in post operative of coronary artery bypass grafting surgery (CABG). However, it9s unknown the breathing pattern (BP) behaviour after inpatient cardiac rehabilitation (CR) program associated to noninvasive ventilation (NIV) during exercises. Aim: To evaluate the BP of post-CABG patients engaged in CR associated to NIV. Methods: Nineteen patients submitted to twice-daily supervised postoperative exercise protocol, which consisted of respiratory exercises and early mobilization (upper and lower limbs exercises and ambulation) with NIV (CPAP= 58,6±8,4yrs) between 9-10 cmH 2 O and without (CG= 58±5,7yrs) were evaluated. BP was assessed by respiratory inductive plethysmography (Lifeshirt system) and analysed by inspiratory (ViVol) and expiratory tidal volume (VeVol); inspiratory, expiratory and total time and thoracoabdominal coordination measures (%RCi and %RCe- percent rib cage inspiratory and expiratory contribution to tidal volume ratio, respectively) in rest sitting position at discharge time. Unpaired Student t test was applied for intergroup analysis (p
Lesson of the week: Low dose methotrexate and bone marrow suppression
Authors: M. Sosin
Journal: BMJ (2003)

Bone marrow suppression can occur even with low doses of methotrexate 

Methotrexate is an antimetabolite that, apart from its use in malignant disorders, is taken orally in low doses for the control of conditions such as rheumatoid arthritis and psoriasis. When used in chemotherapy it causes profound suppression of bone marrow. However, even at a low dose it may be associated with bone marrow suppression—particularly in the presence of renal insufficiency or when other drugs are taken concomitantly (box 1). Its unusual weekly dosing regimen can result in dose error by patients or clinicians. We present three cases of bone marrow suppression in patients taking low dose methotrexate who presented at a district general hospital during a period of four years (table).

View this table:

Details of patients with bone marrow suppression after taking methotrexate



### Case 1

A 78 year old woman with rheumatoid arthritis had been taking a weekly dose of 17.5 mg of methotrexate for two months. Before this the dose had been gradually built up over several years. She was admitted with breathlessness and found to be pancytopenic (haemoglobin concentration 100 g/l, white cell count 3.0 × 109/l, neutrophils 2.5 × 109/l, platelets 13 × 109/l). A month earlier her full blood count had been normal.

Methotrexate treatment was discontinued. She was treated with intravenous folinic acid and antibiotics and was given transfusions of blood products. Her blood count showed recovery (haemoglobin concentration 137 g/l, white …
Employment status and risk of occupational asthma based on job title in a district general severe asthma treatment cohort
Authors: Sarah Diver, Paul Cadden, David Allen, Karl Ballance, Jennifer Hoyle
Journal: European Respiratory Journal (2014)

Introduction: Little is known about employment status (ES) in those receiving omalizumab for severe asthma. Occupational factors contribute in 1 in 6 asthma cases in working age adults 1 .  Objective: We investigate ES and job title (JT) in severe asthma patients on omalizumab.  Method: Retrospective review of 53 patients receiving omalizumab at a district general hospital. Risk of occupational asthma (OA) judged by an experienced occupational lung disease (OLD) physician.  Results: Mean age 41 years, 75% female. 51 (96%) were working age (18-67). ES and JT was known in 47 (92%). 32/47 (68%) employed or in full-time education, 3/15 not working due to asthma, 4/15 not working by choice, 8/15 reasons not documented. 10/47 (21%) were judged high risk for OA by JT: 4 nursing/medical, 1 animal worker, 1 wood dust exposed, 2 flour exposed, 1 hairdresser and 1 cleaner. 3/47 (6%) at lower risk had symptoms causing them to struggle or leave work (call centre, factory worker and scrap metal worker); one seen in OLD clinic. Only 3/53 (6%) had been assessed in OLD clinic (nurse, nursery worker, factory worker).  Conclusions: Treatment outside standard working hours should be considered as a high proportion of patients are currently employed. Closer ties between severe asthma clinics and OLD specialists should be considered for prognostic and economic reasons.  Reference:  1. Nicholson PJ  et al . BOHRF. 2010.