tbuckley/cabot-search huggingface dataset:
Cerebral Palsy–Medicolegal Aspects
Authors: Ivan Blumenthal
Journal: Journal of the Royal Society of Medicine (2001)

In 1862 William James Little, a London orthopaedic surgeon wrote:


‘The object of this communication is to show that the act of birth does occasionally imprint upon the nervous and muscular systems of the nascent infantile organism very serious and peculiar evils. Nearly twenty years ago... I showed that premature birth, difficult labours, mechanical injuries during parturition to head and neck, where life had been saved, convulsions following the act of birth, were apt to be succeeded by a determinate affection of limbs of new-born children, spastic rigidity from asphyxia neonatorum, and assimilated it to the trismus nascentium and the universal spastic rigidity sometimes produced at later periods of existence1.’


This condition was known as Little's disease until William Osler coined the term cerebral palsy in 1888. He too noted the association with difficult deliveries and with asphyxia requiring prolonged resuscitation2. In the 1890s Sigmund Freud was the first to recognize that antepartum and postpartum factors could cause a similar condition. He postulated that most cases arose from difficult birth but speculated that the birth difficulty might have been caused by some underlying condition2. The asphyxia theory was subsequently given impetus when research in monkeys showed that perinatal asphyxia could cause brain damage3.

In the past 30 years, great increases in the use of fetal monitoring and caesarean section have been driven by the belief that early detection of asphyxia and speedy delivery will prevent brain damage. In parallel with these changes there has been an unprecedented rise in malpractice litigation. Surprisingly, over the same period the incidence of cerebral palsy in term infants has not changed4,5. This lack of impact prompted epidemiological studies which showed that asphyxia accounts for less than 10% of cases6. In 1999 an international consensus statement was published to provide an agreed reference for use by the courts and expert witnesses in birth injury litigation7. The intention was to provide a template that could be modified as new knowledge became available8.
Airway foreign body removal by flexible bronchoscope in children: Experience of a Tunisian pediatric respiratory diseases department
Authors: Anissa Berraies, Besma Hamdi, Houda Snen, Imen Sahnoun, Jamel Ammar, Taher Mestiri, Agnes Hamzaoui
Journal: European Respiratory Journal (2014)

Objectives:  To evaluate the experience with the flexible bronchoscopic management of airway foreign bodies (FB) in children (age ≤ 16 years).   Design:  All pediatric bronchoscopies performed in the Pavillon B of Abderrahman Mami Hospital of Ariana from 2002 through 2014 with confirmed FB were reviewed. FB removed by flexible bronchoscope, techniques used and complications were analyzed.   Results:  Of the 76 children with FB, the flexible bronchoscope allowed FB extraction in 15 children. It was used as first line to extract the FB in 6 patients, in 6 patients in whom the rigid bronchoscopic procedure was unsuccessful and in 3 patients in whom the rigid bronchoscopy failed to visualize the FB. In two children, extraction failed and removal was made by bronchotomy in one case and by rigid bronchoscopy in the other one. FB were non-organic in 8 cases, among them 3 head scarf pins. Flexible bronchoscopy was performed through an endotracheal tube in 14 children under general anesthesia. In the other child, the procedure was accomplished under local anesthesia. The extraction instruments employed included baskets forceps and biopsy forceps.  No major complications occurred, only one children developed laryngeal edema that resolved with medical therapy.   Conclusions:  Flexible bronchoscopic extraction of pediatric FB can be performed safely with minimal risks and complications. In our experience, it was successful in 88% of cases. Nevertheless, we caution that it must be performed by an experienced bronchoscopist in the operating room and in the presence of a trained anesthetist.
THE INTERNAL ENVIRONMENT AND BEHAVIOR
Authors: EDWARD F. ADOLPH
Journal: American Journal of Psychiatry (1941)

Internal environment and overt behavior present a reciprocal relation, for the constancy of the body's composition and function depends on behavior for its maintenance, and behavior in turn depends on the body's contents and physiological states. With respect to water, elimination of excesses and replacement of shortages are symmetrical aspects of recoveries and adjustments of water content. Each is quantitatively related to the other in a kinetic pattern that is but rarely incomplete, even in diseased states. Bernard said (1878, p. 113): "The fixity of the internal medium presupposes an arrangement in the organism such that the variations are at each instant compensated and equilibrated." This arrangement I have tried to describe.
Sputum gene expression of mast cell tryptase and carboxypeptidase A3 are increased in eosinophilic asthma
Authors: Katherine Baines, Jodie Simpson, Lisa Wood, Rodney Scott, Peter Gibson
Journal: European Respiratory Journal (2011)

Rationale:  Little is known regarding the presence and activity of mast cells in the airway lumen across asthma inflammatory phenotypes. Sputum gene expression of the mast cell specific proteases may serve as markers of mast cell activation in asthma.   Objective:  To investigate if sputum gene expression of mast cell specific proteases is associated with asthma inflammatory phenotype.   Methods:  Induced sputum was collected from participants with asthma (n=59; eosinophilic n=17; neutrophilic n=12; mixed granulocytic n=12; and paucigranulocytic n=18) and healthy controls (n=17). Gene expression profiles were generated (Illumina Humanref-8 V2) from sputum RNA. Mast cell tryptase (TPSAB1), carboxypeptidase A3 (CPA3) and chymase (CMA1) data were extracted and investigated for their relationship to asthma phenotype.   Results:  Gene expression of tryptase and carboxypeptidase A3 was significantly different among the 5 groups (p   Conclusions:  Gene expression of mast cell tryptase and carboxypeptidase A3 is increased in eosinophilic asthma. Airway mast cells are important in eosinophilic asthma and have a unique phenotype associated with expression of tryptase and carboxypeptidase A3 but not chymase.
Grand Rounds--Hammersmith Hospital: Thromboembolic occlusion of a pulmonary arteriovenous malformation
Authors: I. Sabroe
Journal: BMJ (1995)

always beneficial and may present unwanted reactions (nocebo effects). ConclusionAlthough essential in most clinical trials, a clear distinction is still lacking between placebo and un- treated control groups as well as between perceived and true placebo effects.When describing a placebo response, one must account for the natural course of the disease, the regression towards the mean, and other non-specific effects.The resulting true placebo response is highly variable between studies and may, in many cases, be substantially smaller than the perceived placebo effect.More research should be directed towards better understanding of the complex boundary conditions that may interact and determine the true placebo effect.The best way to achieve this is the inclusion of a second, untreated control group in placebo controlled trials provided that there are no ethical objections.
Histopathological and immunophenotypical criteria for the diagnosis of Sézary syndrome in differentiation from other erythrodermic skin diseases: a European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force Study of 9
Authors: C.D. Klemke, N. Booken, C. Weiss, J.P. Nicolay, S. Goerdt, M. Felcht, C. Géraud, W. Kempf, C. Assaf, N. Ortonne, M. Battistella, M. Bagot, R. Knobler, P. Quaglino, B. Arheiliger, M. Santucci, P. Jansen, M.H. Vermeer, R. Willemze
Journal: British Journal of Dermatology (2015)

Patients with erythrodermic disease are a diagnostic challenge regarding the clinical and histological differential diagnosis.To evaluate histopathological and immunohistochemical diagnostic markers for Sézary syndrome.Ninety-seven erythrodermic cases [Sézary syndrome (SS), n = 57; erythrodermic inflammatory dermatoses (EIDs), n = 40] were collected by the EORTC Cutaneous Lymphoma Task Force histopathology group. Evaluation criteria were (i) epidermal and dermal changes; (ii) morphology of the infiltrate; (iii) immunohistochemical analysis of marker loss (CD2, CD3, CD4, CD5 and CD7); (iv) bystander infiltrate by staining for CD8, FOXP3 and CD25; and (v) expression of Ki-67, CD30, PD-1 and MUM-1.The workshop panel made a correct diagnosis of SS in 51% of cases (cutaneous T-cell lymphoma 81%) and of EID in 80% without clinical or laboratory data. Histology revealed a significantly increased degree of epidermotropism (P < 0.001) and more intraepidermal atypical lymphocytes (P = 0.0014) in SS biopsies compared with EID. Pautrier microabscesses were seen only in SS (23%) and not in EID (P = 0.0012). SS showed significantly more dermal cerebriform and blastic lymphocytes than EID. Immunohistochemistry revealed a significant loss of CD7 expression (< 50%) in 33 of 51 (65%) cases of SS compared with two of 35 (6%) EID (P < 0.001). The lymphocytic infiltrate in SS skin samples was found significantly to express PD-1 (P = 0.0053), MUM-1 (P = 0.0017) and Ki-67 (P < 0.001), and showed less infiltration of CD8(+) lymphocytes (P < 0.001). A multivariate analysis identified CD7 loss, increased numbers of small cerebriform lymphocytes, low numbers of CD8(+) lymphocytes and increased proliferation (Ki-67(+) lymphocytes) as the strongest indicators for the diagnosis of SS.A number of different histological and immunophenotypical criteria are required to differentiate between SS and EIDs.
Brief-Duration High-Intensity Chemotherapy for Patients With Small Noncleaved–Cell Lymphoma or FAB L3 Acute Lymphocytic Leukemia: Results of Cancer and Leukemia Group B Study 9251
Authors: Edward J. Lee, Gina R. Petroni, Charles A. Schiffer, Carl E. Freter, Jeffrey L. Johnson, Maurice Barcos, Glauco Frizzera, Clara D. Bloomfield, Bruce A. Peterson
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To define the activity and feasibility of brief-duration high-intensity chemotherapy for adults with small noncleaved, non-Hodgkin’s lymphoma (SNC) and the L3 variant of acute lymphocytic leukemia (L3 ALL). PATIENTS AND METHODS: Seventy-five adults with either SNC or L3 ALL (median age, 44 years) were treated with an aggressive regimen that consisted of one cycle of cyclophosphamide and prednisone followed by cycles containing either ifosfamide or cyclophosphamide; high-dose methotrexate, vincristine, dexamethasone, and either doxorubicin or etoposide/cytarabine; or intrathecal triple therapy with prophylactic CNS irradiation. RESULTS: All 24 patients with L3 ALL and the 30 of 51 patients with SNC confirmed by central histologic review were included in this analysis. Forty-three of 54 patients achieved complete response (CR) (18 of 24 with ALL and 25 of 30 with SNC), and 28 are alive and in continuous CR with a median follow-up of 5.1 years. Hematologic toxicity was profound, and nonhematologic toxicity was notable, with 10 of 75 patients treated developing significant neurologic toxicity consisting of transverse myelitis in five patients, CNS toxicity in three, and severe peripheral neuropathy in two. All patients who did not achieve CR died of the disease, and all recurrences occurred within 16 months of the end of treatment. Responses and toxicities were similar in the patients with both lymphoma and leukemia. CONCLUSION: Aggressively delivered chemotherapy is potentially curative in as many as half of patients with SNC and the L3 ALL variant. This treatment regimen had considerable neurologic toxicity and has been modified.
Activity of cefepime and carbapenems in experimental pneumonia caused by porin-deficient Klebsiella pneumoniae producing FOX-5 β-lactamase
Authors: C. Pichardo, M. del Carmen Conejo, M. Bernabéu-Wittel, A. Pascual, M.E. Jiménez-Mejías, M. de Cueto, M.E. Pachón-Ibáñez, I. García, J. Pachón, L. Martínez-Martínez
Journal: Clinical Microbiology and Infection (2005)
Thymoma: State of the Art
Authors: Charles R. Thomas, Cameron D. Wright, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (1999)

Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia, and pure red cell aplasia. The rarity of this tumor, however, has somewhat obscured the optimal treatment for this disease. For the majority of patients who present with localized tumor, surgical extirpation remains the standard of choice. Adjuvant radiotherapy seems to improve local control and survival. In more advanced disease, systemic therapy has been demonstrated to produce a 50% to 80% objective response rate. These observations have led to the development of multimodality therapy for the treatment of patients with advanced thymoma. In this article, we will review the current perspectives on the management of early stage and advanced thymoma.
Total body irradiation for stage II-IV non-Hodgkin's lymphoma: ten-year follow-up.
Authors: N P Mendenhall, W D Noyes, R R Million
Journal: Journal of Clinical Oncology (1989)

Between 1972 and 1977, a prospective study was conducted at the University of Florida on the role of total body irradiation (TBI) in the management of stage II-IV non-Hodgkin's lymphoma (NHL). Forty-four consecutive de novo (DN) patients (including ten stage II, 18 stage III, and 16 stage IV), as well as 16 previously treated (PT) patients, were accrued. Twenty of the 44 DN patients were symptomatic at presentation. Complete clinical responses were obtained in 20 of the 27 DN patients with favorable histologies (FH), and six of the 17 with unfavorable histologies (UH). Partial responses were obtained in six patients with FH and 11 patients with UH; only one patient showed no response to TBI. By univariate analysis, PT patients showed a trend for decreased relapse-free survival (P = .066) and decreased survival (P = .093). Multivariate analysis identified the best predictors of response rate to be histology (P = .0146) and marrow involvement (P = .0854); of relapse-free survival, histology (P = .0035), and TBI dose (P = .002); and of absolute survival, age (P = .0012), histology (P = .012), and TBI dose (P = .029). Thirty of the 41 patients who relapsed underwent salvage treatment with either chemotherapy or radiation. Twenty-three of the 30 undergoing salvage therapy obtained a second complete clinical response. There were no treatment-related deaths. The most common complication was thrombocytopenia. The major late complications were myeloproliferative disorders in four patients, which occurred only after cumulative TBI doses in excess of 200 cGy.
Optimal circadian time of vinorelbine (V) combined with chronomodulated 5-FU in pretreated metastatic breast cancer patients. EORTC 05971 randomized multicenter study
Authors: B. Coudert, C. Focan, D. Genet, S. Giacchetti, M. Lentz, S. Marreaud, B. Baron, T. Gorlia, F. Lévi
Journal: Journal of Clinical Oncology (2006)

2066 Background: Chronotherapy is an aim to increase efficacy/toxicity ratio. Objectives: to define the dosing least toxic time (DLTT) of V (30 mg/m 2 /d at D1 and D6), combined with chrono 5-FU (10 pm-10 am) (850 mg/m 2 D2-D5) over 3 courses q3w. Methods: A logistic regression model (LRM) estimated the DLTT assuming a sinusoidal distribution over time (i.e. over the 8 different arms) of the toxicity rate observed in each arm. The associated 90% confidence limits (CL) has been obtained by bootstrap method. Results: 90 patients were recruited. Toxicity in 46 pts led to the V dosage reduction to 25 mg/m 2 /d. 40 and 43 pts were assigned the V30 and the V25 regimen. 12% pts went off for toxicity, 5% for PD, 1% for refusal, 1% for unrelated death. 224 cycles were analyzed . V and 5FU relative dose intensities were 79.4% and 78.2% in the V30 while 88.1% and 87.4% in the V25 pts. Over the 3 cycles, toxicity by cycle was: Grade (G) 3 and G4 leucopenia in 47% and 29%, G3 and G4 neutropenia in 12% and 77%. G3 febrile neutropenia in 34%. G2 thrombopenia and anemia in 4% each. Other G3 and G 4 toxicity were stomatitis (12%), alopecia (7%), and less than 5%: cardiovascular, lethargy, diarrhea, constipation, other gastrointestinal, infection, sensory, pulmonary. LRM could not demonstrate a DLTT for the neutropenia G3–4 incidence, the primary endpoint. However, based on the stratified by dose analysis, a 90% CI of less than 6 hours width was observed: - around 17H17 [14H04–20H03] for the incidence of leucopenia G3–4. - around 8H16 [06H04–10H39] for tolerability (dose reduction, dose delay or treatment interruption for toxicity reason). This suggests that treatment tolerability was influenced by other factors beside leucopenia nadir. No other 90% CI of less than 6 hours width could be observed for other toxicity endpoints. Conclusions: Using a novel time finding study design with ad hoc statistics, this first randomized multicenter study has determined a DLTT for Vinorelbine in 90 women with MBC. Additional studies are ongoing to further assess the relevance of this trial design method that could prove useful for improving the safety of anticancer drugs during their clinical development. Support Pierre Fabre Oncology, Ligue Bourguignonne contre le Cancer No significant financial relationships to disclose.
Breast-Conserving Therapy: Proteases as Risk Factors in Relation to Survival After Local Relapse
Authors: Marion E. Meijer-van Gelder, Maxime P. Look, Joan Bolt-de Vries, Harry A. Peters, Jan G.M. Klijn, John A. Foekens
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate whether cathepsin D, urokinase-type plasminogen activator (uPA), its inhibitor, plasminogen activator inhibitor-1 (PAI-1), or clinical factors can predict which patients are at risk for developing distant metastases after local recurrence (LR). PATIENTS AND METHODS: Of 1,630 patients treated with breast-conserving surgery and radiotherapy of the breast between 1980 and 1992, LR developed in 171 as a first event. From the available primary tumor tissues, we determined the cytosolic levels of cathepsin D, uPA and PAI-1. RESULTS: In patients with LR, a short (≤ 2 years) disease-free interval (DFI) and skin involvement of LR were associated with poor postrelapse distant metastasis-free survival (PR-DMFS, P = .001, both) and postrelapse overall survival (PR-OS; P &lt; .0001 and P &lt; .0002, respectively). The primary tumor levels of uPA and PAI-1 were elevated for patients with a short DFI (P &lt; .01), but such a relation was not observed for patients with skin involvement. In univariate analyses, high levels of uPA and PAI-1 in the primary tumor were associated with poor PR-OS (P = .038 and P = .040, respectively) but not PR-DMFS. In Cox multivariate analyses for PR-DMFS and PR-OS, only a short DFI and skin involvement of the LR were independently associated with a poor clinical outcome. CONCLUSION: In patients treated with breast-conserving therapy who had LR as a first event, a short DFI and skin involvement were strong indicators for poor PR-DMFS and PR-OS. The proteases studied did not contribute significantly to the final multivariate model.
Abstract 16884: Clonal Analysis of Hematopoietic Stem Cell Transdifferentiation in the Regenerated Myocardium
Authors: Fumihiro Sanada, Kim Junghyun, Sergio Sinore, Kazuya Isobe, Joao Ferreira-Martins, Christian Arranto, Ramaswamy Kannapan, Maria Cimini, Alex Matsuda, Donato Cappetta, Ada Pesapane, Mario Ricciardi, Giorgia Palano, Polina Goihberg, Marcello Rota, Toru Hosoda, Jan Kajstura, Piero Anversa, Annarosa Leri
Journal: Circulation (2012)
Audit on pleural procedure in UK district general hospital
Authors: Amrithraj Bhatta, Imran Satia, Ram Sundar, Imran Aziz
Journal: European Respiratory Journal (2011)

Introduction:  Intercostal Chest Drain (ICD) insertion is an invasive procedure indicated in certain emergency and elective scenarios. The practice is changing with more importance given to training, safety and use of ultrasound image guidance.   Aims:  The aim of this audit was to access current awareness & training level of junior doctors and level of practice.   Methods and results:  First part of audit includes questionnaire survey on awareness and competency. Of the 26 respondent, 61% were independently competent at ICD insertion, but only 9% of them performed more than 10 procedures in last one year. Only 23% of doctors had thoracic ultrasound training.  In the second part, 38 consecutive cases were audited retrospectively (male = 76%, female = 24%).Pleural effusion (59%) and pneumothorax (31%) accounted for most of the indications. 38% of the procedures performed out of hours and all of them were justified. Only 68% had any form of consent documented. Majority (85%) were inserted by senior doctors (ST3+ level). Bedside Ultrasound was used in 80% of pleural effusion cases. The nursing drain observation chart was maintained in 88% cases. 8% minor immediate complication reported, no death or organ damage directly related to the procedure.   Discussion:  This audit has demonstrated improving safety awareness that includes, most of procedure performed by trained doctors and use of bedside ultrasound. But it has highlited lack of training at junior doctors level,including thoracic ultrasound. Following this audit we have introduced the safety check list and training programme for junior doctors including thoracic ultrasound technique.   References:   1T Havelock, BTS Pleural procedure guidelines 2010.  2NPSA Rapid response Report- NPSA/2008/RRR003.
Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial
Authors: Jean-Michel Gracies, Allison Brashear, Robert Jech, Peter McAllister, Marta Banach, Peter Valkovic, Heather Walker, Christina Marciniak, Thierry Deltombe, Alexander Skoromets, Svetlana Khatkova, Steven Edgley, Fatma Gul, France Catus, Beatrice Bois De Fer, Claire Vilain, Philippe Picaut
Journal: The Lancet Neurology (2015)