tbuckley/cabot-search huggingface dataset:
Heterozygous Germline <i>ATM</i> Mutations Do Not Contribute to Radiation-Associated Malignancies After Hodgkin's Disease
Authors: Kim E. Nichols, Seth Levitz, Kristen E. Shannon, Doke C.R. Wahrer, Daphne W. Bell, Gloria Chang, Sanjay Hegde, Donna Neuberg, Timothy Shafman, Nancy J. Tarbell, Peter Mauch, Chikashi Ishioka, Daniel A. Haber, Lisa Diller
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The successful treatment of Hodgkin's disease has been associated with an increased incidence of secondary malignancies. To investigate whether genetic factors contribute to the development of secondary tumors, we collected family cancer histories and performed mutational analysis of the ataxia-telangiectasia (AT) gene, ATM, in a cohort of Hodgkin's disease survivors with secondary malignancies. ATM was chosen for evaluation because of the increased radiosensitivity of cells derived from AT patients and obligate heterozygotes and the epidemiologic observation that AT carriers are at increased risk for radiation-induced breast cancer. PATIENTS AND METHODS: Fifty-two patients who developed one or more neoplasms after treatment for Hodgkin's disease participated in this study. Personal and family histories of cancer were obtained through patient interviews and review of medical records. ATM mutational analysis was performed using a yeast-based protein truncation assay. RESULTS: Seventy-six secondary neoplasms were observed in this cohort of 52 Hodgkin's disease survivors, with 18 patients (35%) developing more than one secondary neoplasm. Positive family histories of cancer were present in 11 (21%) of 52 patients, compared with three (4%) of 68 Hodgkin's disease patients in a comparison cohort who did not develop secondary neoplasms (P = .008; Fisher's exact test). No germline ATM mutations were identified, resulting in an estimated AT carrier frequency in this population of 0% (90% confidence interval, 0% to 4%). CONCLUSION: Analysis of the number of tumors per individual and the family history of cancer in our cohort suggests that genetic factors may contribute to development of secondary neoplasms in a subset of Hodgkin's disease survivors. Mutational analysis, however, does not support a significant role for heterozygous truncating ATM mutations. Future studies evaluating other genes involved in DNA damage response pathways are warranted.
Primary care and the NHS white papers
Authors: J. Chisholm
Journal: BMJ (1998)

Before last year's election the Labour Party made much of its intention to move away from the fragmentation allegedly caused by the previous government's NHS reforms and to return to a truly national health service. However, as the new government's proposals have been revealed, it is all too apparent that its commitment to devolution exceeds its commitment to the recreation of a national service. The differences in the organisation and nature of the service between the four parts of the United Kingdom are to be increased, and in particular health care in Scotland will diverge, with complete exclusion of general practitioners from the process of commissioning care.

Over the past six months a succession of white and green papers have spelt out the proposals for NHS reform1–4and strategic improvements in public health.5–7 These have emphasised a service that is fairer, distributes resources more equitably, eliminates two tierism, is needs led, better integrates health and social services, is based on cooperation rather than competition, reinstates strategic planning, emphasises quality, addresses health inequalities, promotes better health, and involves the public. Thus, at the headline level, the proposals have secured wide endorsement, from both the public and health professions.

However, it has been all too apparent that the detail has …
Clinicopathologic Re-Evaluation of 100 Malignant Fibrous Histiocytomas: Prognostic Relevance of Subclassification
Authors: Christopher D.M. Fletcher, Pelle Gustafson, Anders Rydholm, Helena Willén, Måns Åkerman
Journal: Journal of Clinical Oncology (2001)

Malignant fibrous histiocytoma (MFH) has been regarded as the most common soft tissue sarcoma (STS) in adults. Yet its true nature and the validity of this diagnostic concept have increasingly been questioned. Available data suggest that most patients with MFH can be subclassified into specific STS types, but the clinical relevance of such categorization has been argued. In a retrospective study, we reclassified 100 tumors of the extremity and trunk wall primarily diagnosed as MFH and analyzed the outcome.Patients were adults (median age, 70 years; range, 32 to 94 years). The median tumor size was 8 cm (range, 1 to 30 cm), and the thigh was the most common tumor location (n = 31). Median follow-up was 8 years (range, 3 to 16 years). The overall 5-year metastasis-free survival rate was 0.64. The tumors were reanalyzed histologically, immunohistochemically, and, where available, ultrastructurally, and were classified according to strict diagnostic criteria. Patients were staged according to the American Joint Committee on Cancer system, and prognoses were compared among different groups of the reclassified diagnoses, paying special attention to myogenic tumors.In 84 of 100 tumors, a specific line of differentiation was either proved or strongly suggested. The most common diagnoses were myxofibrosarcoma (n = 22) and leiomyosarcoma (n = 20). Overall, 30 tumors could be grouped as some form of myogenic sarcoma. These tumors had a worse prognosis, even within the same American Joint Committee on Cancer stage, and a shorter time to metastasis than nonmyogenic tumors.This retrospective study confirms that most so-called MFH can be subclassified by defined criteria; it provides evidence that such classification is clinically important. Specifically, pleomorphic STS showing myogenic differentiation are significantly more aggressive, a finding that allows planning future therapeutic trials.
Initial phase I evaluation of the novel thymidylate synthase inhibitor, LY231514, using the modified continual reassessment method for dose escalation.
Authors: D A Rinaldi, H A Burris, F A Dorr, J R Woodworth, J G Kuhn, J R Eckardt, G Rodriguez, S W Corso, S M Fields, C Langley
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the toxicities, maximal-tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of LY231514, a novel thymidylate synthase (TS) inhibitor. PATIENTS AND METHODS Patients with advanced solid tumors were administered LY231514 intravenously over 10 minutes, weekly for 4 weeks, every 42 days. Dose escalation was based on the modified continual reassessment method (MCRM), with one patient treated at each minimally toxic dose level. Pharmacokinetic studies were performed in all patients. RESULTS Twenty-five patients were administered 58 courses of LY231514 at doses that ranged from 10 to 40 mg/m2/wk. Reversible neutropenia was the dose-limiting toxicity. Inability to maintain the weekly treatment schedule due to neutropenia limited dose escalation on this schedule. Nonhematologic toxicities observed included mild fatigue, anorexia, and nausea. At the 40-mg/m2/wk dose level, the mean harmonic half-life, maximum plasma concentration, clearance, and apparent volume of distribution at steady-state were 2.02 hours, 11.20 micrograms/mL, 52.3 mL/min/m2, and 6.64 L/m2, respectively. No major antitumor responses were observed; however, minor responses were achieved in two patients with advanced colorectal cancer. CONCLUSION The dose-limiting toxicity, MTD, and recommended phase II dose of LY231514 when administered weekly for 4 weeks every 42 days are neutropenia, 40 mg/m2, and 30 mg/m2, respectively.
Surgical salvage of chemorefractory germ cell tumors.
Authors: B R Murphy, E S Breeden, J P Donohue, J Messemer, W Walsh, B J Roth, L H Einhorn
Journal: Journal of Clinical Oncology (1993)

PURPOSE Patients with disseminated germ cell tumors who relapse after salvage chemotherapy, or who progress during cisplatin-based therapy, have chemorefractory disease and a very poor prognosis. A subset of these patients will have chemorefractory but resectable disease. We have therefore evaluated the role of salvage surgery in this patient population. PATIENTS AND METHODS We performed a retrospective review of all patients with disseminated germ cell tumors who were felt to have chemorefractory disease and underwent salvage surgery from 1977 to 1990 at Indiana University. All patients had elevated serum markers or other signs of progressive carcinoma. A total of 48 patients underwent surgery (33 retroperitoneal lymph node dissections [RPLNDs], six thoracotomies, three thoracoabdominal resections, and multiple asynchronous procedures in six patients). RESULTS Thirty-eight of 48 patients (79%) were rendered grossly free of disease and 29 (60%) obtained a serologic remission. Ten patients (21%) remain continuously disease-free with no postoperative treatment with a median follow-up of 46 months (range, 31 to 89). Six additional patients who relapsed after salvage surgery are currently disease-free with further treatment (four with repeat surgery and two with high-dose chemotherapy and autologous bone marrow transplantation [ABMT]). CONCLUSION Selected patients with chemorefractory but resectable germ cell tumors have definite potential for cure with salvage surgery.
Series on education: What competence does a rheumatologist need?: an international perspective
Authors: B. Amor
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To forecast, on the basis of the past and present position of rheumatologists in Europe, the competence needed in the future to secure and promote the specialty within the healthcare network. <h3>METHODS</h3> Union Européenne des Médecins Spécialistes/European Board of Rheumatology (UEMS/EBR) questionnaire on (<i>a</i>) training centres in Europe, (<i>b</i>) rheumatologists9 skills, (<i>c</i>) UEMS core curriculum. <h3>RESULTS</h3> 173 training centres in rheumatology were identified. Reponses to the questionnaire showed both harmony and diversity in the practice of rheumatology. Harmony arises from the need to (<i>a</i>) have an extensive and profound knowledge of, and clinical experience with, all the causes of painful or disabled locomotor apparatus; (<i>b</i>) manage such disorders in the most cost effective way; and (<i>c</i>) promote "shared clinical decision making". The diversity seen both among and within the European countries is due to the different activities of rheumatologists. <h3>CONCLUSION</h3> Rheumatological competence must be based on a common core, as described in the UEMS core curriculum, and on deeper and diverse clinical or scientific knowledge covering the entire field of the specialty, to secure its flexibility and resilience in the market place and to promote its scientific development.
Evolving characteristics of toxoplasmosis in patients infected with human immunodeficiency virus-1: clinical course and Toxoplasma gondii-specific immune responses
Authors: C. Hoffmann, M. Ernst, P. Meyer, E. Wolf, T. Rosenkranz, A. Plettenberg, A. Stoehr, H.-A. Horst, K. Marienfeld, C. Lange
Journal: Clinical Microbiology and Infection (2007)
Acne: Diagnosis and Management
Authors: Calum C Lyon
Journal: Journal of the Royal Society of Medicine (2001)

Professors Cunliffe and Gollnick have produced a useful highly illustrated handbook for clinicians who manage patients with acne and related disorders. Although much of it deals with diagnosis and management (as the title indicates), almost a quarter is taken up with an in-depth account of the pathophysiology and microbiology of acne. This section gives up-to-date information on the routine and experimental techniques that can be used to investigate acne, perhaps directed largely at those doing skin research. On this theme it describes experimental evidence on the nature of the early inflammation in acne lesions and how disruption of the pilosebaceous follicle might result in an ongoing, cellmediated, antigen-dependent immune response.

Since the target readership clearly includes dermatologists as well as general practitioners and other clinicians (hospital-based treatments such as roaccutane are included) the book would have benefited from more discussion of individual complications such as acne fulminans and inflammatory sinuses or cysts, but the common features of acne are handled very thoroughly. Much of the remainder of the book offers a detailed account of modern therapies for acne, including recent evidence for the efficacy and safety of the individual topical and systemic agents. This is particularly important in the areas of antibiotic-resistant Propionibacterium acnes, autoimmune and other side-effects of systemic tetracyclines and the safety of long-term systemic retinoids. These subjects are handled very clearly. Acne subtypes and the range of differential diagnoses are also well covered. This section will be especially useful to the non-dermatologist since it includes management options for many of these conditions as well as clinical descriptions and an atlas of clinical photographs.

Schering Health Care sponsored the book and some of their acne medications are mentioned by tradename rather than by generic name alone. However, perhaps for balance, one or two other treatments also include the tradename. There is certainly no bias towards the sponsoring company's treatments. In summary—a very well presented and well illustrated textbook.
Adaptive strategies and recovery from rape
Authors: Ann Wolbert Burgess, Lynda Lytle Holmstrom
Journal: American Journal of Psychiatry (1979)

The authors conducted a follow-up study of 81 rape victims to analyze the effect of adaptive or maladaptive response to rape on recovery over a 4-6 year period. They found that victims recovering fastest used more adaptive strategies, including positive self-assessment; defense mechanisms of explanation, minimization, suppression, and dramatization; and increased action. Victims who had not yet recovered had more maladaptive mechanisms, such as negative self-assessments, inaction, substance abuse, and action on suicidal thoughts.
Plasmablastic Lymphomas of the Oral Cavity: A New Entity Associated With the Human Immunodeficiency Virus Infection
Authors: H.J. Delecluse, I. Anagnostopoulos, F. Dallenbach, M. Hummel, T. Marafioti, U. Schneider, D. Huhn, A. Schmidt-Westhausen, P.A. Reichart, U. Gross, H. Stein
Journal: Blood (1997)
Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation.
Authors: O W Press, R Livingston, J Mortimer, C Collins, F Appelbaum
Journal: Journal of Clinical Oncology (1991)

Combination chemotherapy is capable of curing many patients with newly diagnosed intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of relapsed NHL remains problematic. Bone marrow transplantation (BMT) offers the best chance for disease-free survival, but interim chemotherapy is often necessary while awaiting BMT, especially for patients with bulky disease. We report here 39 patients (median age, 44 years) who failed primary therapy with doxorubicin-based regimens and subsequently were treated with one to six cycles of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100 mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x two doses on day 2 (DHAP) before the planned BMT. Histologies included 16 diffuse large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic, and eight other. Twenty-eight patients had stage IV disease, 13 had B symptoms, and 20 had an elevated lactate dehydrogenase (LDH). Patients had been treated with a median of three previous chemotherapy regimens. Sixty-one percent of patients had high tumor burdens according to the MD Anderson criteria. Objective responses to DHAP were seen in 26 patients (67%) including nine complete responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted a median of 7.5 months. Myelosuppression was the major toxicity, but there were no treatment-related deaths. To date, 17 patients have undergone subsequent BMT with a projected 3-year disease-free survival of 15%. We conclude that the DHAP regimen is effective short-term salvage therapy for relapsed NHL patients, but the long-term prognosis of multiply relapsed patients remains poor.
Late-breaking abstract: Profiling of single maintenance and reliever therapy (SMART) dosing instructions of budesonide/formoterol (BFC) in clinical practice
Authors: Rachael DiSantostefano, Nada Boudiaf, David Stempel, Neil Barnes
Journal: European Respiratory Journal (2014)

Rationale:  To describe clinical trends in dosing instructions for SMART for BFC in asthma.   Methods:  This study examined dosing instructions for BFC in asthma based on the CPRD-GOLD data (2009-2013), a primary care database in the United Kingdom. Patient prescriptions of BFC and short-acting beta-agonists (SABA) were described for one year from the index BFC prescription. SMART dosing was determined when prescription instructions indicated twice daily dosing with i°and when requiredi±.   Results:  There were 119,802 BFC prescriptions in 14,818 patients, where    Conclusions:  These results demonstrate that SMART dosing for BFC were rarely prescribed according to electronic medical records in patients with asthma (1.2% or 173 of 14,818) in UK clinical practice, as noted in earlier work (Boyter, Respir Med. 2011 Jun;105(6):864-8). Of those with SMART instructions, most patients still were prescribed rescue inhalers and similar amounts of BFC than those patients without SMART dosing.  (GSK-funded, PJ2269)
Abstract 17613: Bivalirudin Leads to Less Major Bleeding but Does Not Reduce Major Cardiovascular Outcomes in Diabetes Patients Undergoing Percutaneous Coronary Intervention. A Pooled Analysis of Randomized Trials
Authors: Ramez Nairooz, Partha Sardar, Suarav Chatterjee, Hossam Amin, Shobhana Chaudhari, Ferdinand Visco
Journal: Circulation (2013)
CALGB 170601: A phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy (CIPN).
Authors: Ellen M. Lavoie Smith, Herbert Pang, Constance Cirrincione, Stewart Barry Fleishman, Electra D. Paskett, Camilo E. Fadul, Chetaye Knox, Charles L. Shapiro, Paul Gilman
Journal: Journal of Clinical Oncology (2012)

CRA9013 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Abstract 21362: Association Between Recovery of Left Ventricular Function After Acute Myocardial Infarction With Severity and Type of Sleep Apnea
Authors: Stefan Buchner, Tanja Greimel, Kurt Debl, Andreas Luchner, Anna Satzl, Okka W Hamer, Astrid Novak-Brandl, Astrid Braune, Ruth Obermeier, Michael Pfeiffer, Gunter Riegger, Michael Arzt
Journal: Circulation (2010)

Rationale: Impaired cardiac function may promote the development of sleep apnea (SA). The aim of this study was to determine whether changes of left ventricular ejection fraction (LVEF) after acute...
Abnormal cone synapses in human cone-rod dystrophy
Authors: Kevin Gregory-Evans, Robert N Fariss, Daniel E Possin, Cheryl Y Gregory-Evans, Ann H Milam
Journal: Ophthalmology (1998)

ObjectiveLittle is known of the cytopathology of photoreceptors in human inherited retinal dystrophies that initially affect the central retina, including the macula. The current study sought to determine the cytologic features of dysfunctional cone and rod photoreceptors, as well as the pattern of degeneration of the cells in representative cases of central retinal dystrophy.Study designComparative human tissue study.MaterialsFour human donor eyes with the following forms of central retinal dystrophy: cone-rod dystrophy (CRD), central areolar choroidal dystrophy, Bardet-Biedl syndrome, and cone dystrophy-cerebellar ataxia. The cytologic features of retinal photoreceptors in these eyes were compared with those in an eye with retinitis pigmentosa and six normal human eyes.Methods and outcome measuresImmunocytochemistry and electron microscopy were used to evaluate the retinal histopathology in the donor eyes.ResultsCone numbers were decreased in the case of CRD, particularly in the central and far peripheral retina, and both cone and rod outer segments were slightly shortened. Occasional degenerate cones had dense cytoplasm and pyknotic nuclei dislocated sclerad to the external-limiting membrane. The most prominent alteration in this retina was marked enlargement and distortion of the cone photoreceptor pedicles, which contained reduced numbers of synaptic vesicles. The retina with central areolar choroidal dystrophy contained a few cones with similarly abnormal synapses. However, comparable cone synapse abnormalities were not observed in the cases of Bardet-Biedl syndrome, cone dystrophy-cerebellar ataxia, retinitis pigmentosa, or in the normal retinas.ConclusionsThe functional consequences of the cone synapse abnormalities in CRD are not known but may correlate with the electroretinographic abnormalities documented in some cases of CRD. To our knowledge, comparable synapse changes have not been noted in either rods or cones in other forms of retinal dystrophy, including retinitis pigmentosa, suggesting that different cytopathologic mechanisms may be involved.
Immune Function in Healthy Relatives of Patients With Malignant Disease 2
Authors: Ruth Dworsky, Joyce Baptista, John Parker, Stebbin Chandor, Gary Noble, Kenneth Herrmann, Werner Henle, Brian Henderson
Journal: JNCI Journal of the National Cancer Institute (1978)

Immune function studies of healthy members of families with multiple lymphoreticular neoplasms were compared with those of healthy members of families with multiple cancers and families with no known history of cancer. The lymphoma family group had a significantly elevated serum level of IgM and diminished responses to the Candida albicans skin test antigen and the T-cell mitogen concanavalin A. Subjects with Epstein-Barr virus-viral capsid antigen titers greater than or equal to 160 had lower responses to mitogens.
Effect of combined therapy with oral azythromicin and betametasone, and nasal budesonide in children with sleep disordered breathing associated with adenotonsillar hypertrophy and rhinosinusitis
Authors: Juan Figueroa, Carlos Velasco Suarez
Journal: European Respiratory Journal (2013)

Background: rhinosinusitis is frequent in children with adenotonsillar hypertrophy (ATH) and it increase the obstruction and inflammation of upper airways.  Objetives: to evaluate if the treatment with oral antibiotic and steroids plus topic steroid can improve Sleep Disordered Breathing (SDB) in this type of patients.  Methods: 25 children with SDB (snoring and apneas confirmed by home video plus nocturnal home oximetry with 2 or more clusters of hypoxemic events) associated with ATH and clinical signs of rhinosinusitis were included. They were treated with 5 days azythromicin + 7 days betametasone + nasal budesonide until a new nocturnal oximetry was performed 3 weeks later.  Results: nocturnal symptoms and the median of all the oximetry variables improve after therapy: hypoxemic events index (7.7vs1.6), minimal SaO2tc (80vs84), % of time with SaO2tc≤90% (2.4vs0.4), and media SaO2tc out of events (97vs98); (sign test p≤0.001). When children were grouped according to events index greater improvement was observed in children with highest events index (Index 1-4 improve: -1.2; 5-10: -5.8; ≥11: -14.5).  Conclusions: combined therapy improve SDB in children with ATH and rhinosinusitis; studies are needed to assess the persistence of this initial improvement.