tbuckley/cabot-search huggingface dataset:
Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination.
Authors: E W Hoskyns, H Simpson, P Monk
Journal: Thorax (1994)

BACKGROUND--BCG vaccination alters the response to tuberculin testing and influences the potential validity of the Heaf test in the diagnosis of tuberculosis. This study used a purified protein derivative 1 tuberculin unit (TU) Mantoux test with a cut off of 5 mm induration as an indicator of tuberculous infection in high risk children to determine whether this would distinguish infection from previous neonatal BCG vaccination. METHODS--Children at high risk of tuberculosis on chest radiography, Heaf test, or contact history who had been screened in the contact tracing clinic and referred for further assessment were included in the study. After clinical examination, chest radiography, and Mantoux testing they were assigned to three groups (tuberculous disease, chemoprophylaxis, or no treatment) and followed up for 6-24 months in the outpatient clinic and subsequently by postal questionnaire. RESULTS--Comparison of the Heaf and Mantoux tests showed a difference in the results with 82% of cases positive by the Heaf test and 59% positive by the Mantoux test. Using the Mantoux test result in combination with clinical and radiographic findings 194 children were allocated to the three groups as follows: primary tuberculosis (5), chemoprophylaxis (101), no treatment (88). During follow up for a mean (range) time of 46 (11-102) months four additional cases received treatment for primary tuberculosis, two in the chemoprophylaxis group and two in the untreated group. CONCLUSIONS--The use of the 1 TU Mantoux test after neonatal BCG vaccination reduced the number of children receiving treatment from 129 to 93-that is, by 36%. Although the numbers are small, there was no increase in the later development of tuberculosis.
Alteration of p53 Pathway in Squamous Cell Carcinoma of the Head and Neck: Impact on Treatment Outcome in Patients Treated With Larynx Preservation Intent
Authors: Iman Osman, Eric Sherman, Bhuvanesh Singh, Ennapadam Venkatraman, Michael Zelefsky, George Bosl, Howard Scher, Jatin Shah, Ashok Shaha, Dennis Kraus, Carlos Cordon-Cardo, David G. Pfister
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To identify the role of p53 pathway alteration(s) as predictors of treatment outcome in patients with advanced, resectable, squamous cell carcinoma (SCC) of the larynx and pharynx treated with larynx preservation (LP) intent. PATIENTS AND METHODS: Seventy-one patients treated on two consecutive LP protocols were studied based on availability of representative tissues. We analyzed the expression pattern of p53, its upstream regulator mdm2, and downstream transcriptional target p21/WAF1 by immunohistochemistry. Positive phenotype was defined as ≥ 20% of tumor cells showing nuclear immunoreactivity. Results were correlated with treatment outcomes. RESULTS: Positive phenotype was observed in 35 (49%) of 71 cases for p53, in 52 (74%) of 70 for mdm2, and in 37 (54%) of 68 for p21. There was no correlation between p53 phenotype and p21 nuclear accumulation. The mdm2-negative phenotype was most predictive of major response at the primary tumor site (P = .088). p53-positive phenotype was associated with worse local control with LP (LCLP; 49% v 23%, P = .053) and inferior overall survival (OS; 51% v 29%, P = .017) at 5 years. On Cox regression analysis, p53-positive phenotype predicted inferior OS (P = .033) and showed a trend for worse LCLP (P = .102). When analyzed in a multivariate model as continuous variables, p53 showed a stronger correlation with inferior OS (P &lt; .01), and mdm2 was associated with worse OS (P &lt; .01). CONCLUSION: Among the three markers studied, our data support p53 phenotype as the most informative predictor of unfavorable outcomes in the LP setting, and suggest a role for mdm2 phenotype that requires further exploration. Our analysis does not support a p53-dependent mechanism for p21 expression. Prospective and larger studies are necessary before integration of these molecular markers as part of molecular staging and predictors for organ preservation or other outcomes.
Carcinoid heart disease: successful tricuspid valve replacement.
Authors: M Honey, M Paneth
Journal: Thorax (1975)

A woman aged 46 was found to have severe tricuspid valve disease 14 years after the diagnosis of a malignant carcinoid tumour of the ileum and 33 years after the onset of symptoms attributable to the disease. Increasing ascites requiring repeated paracentesis had not responded to chemotherapy including infusion of 5-fluorouracil and vincristine into the coeliac artery. The tricuspid valve was replaced by a Björk-Shiley prosthesis. After operation there was no recurrence of ascites or oedema. She remains well one year and 11 months later. It is suggested that valve replacement surgery should be considered more often in patients with carcinoid heart disease. Hepatomegaly and ascites sould not be attributed too readily to advancing malignant disease without careful consideration of the role of right-sided valvar lesions in the production of these signs.
The use of surgical services in the management of suspected lung cancers
Authors: Anob Chakrabarti, Martin Hayward, Sajid Khan
Journal: European Respiratory Journal (2012)

Introduction 

The National Lung Cancer Audit Report 2011 identified an average surgical rate of 14% in England and Wales. This focuses on potentially curative surgery (with the exception of mesothelioma) and so does not encompass the full breadth of surgical intervention undergone by our patients. This study aimed to describe this spectrum for our patient population in a secondary care setting.

Method 

The electronic patient record system was searched for all patients discussed at multidisciplinary meetings in 2010. Data was gathered from letters, operation notes and meeting minutes on the system.

Results 

1172 cases were discussed of which 212 (18%) had confirmed lung cancer. In these, 74 (37.7%) procedures were performed. 1.4% of patients had two procedures. 8.0% had a lobectomy, 4.7% a wedge resection or segmentectomy, 14.6% a VATS drainage of effusion, biopsy and/or pleurodesis (4.2% for mesothelioma) and 5.2% other procedures. For 2.4% there was no data.

After surgery, histology revealed NSCLC in 52.7%, mesothelioma in 13.5%, SCLC in 2.7%, carcinoid in 1.4% and no malignancy in 6.8%. In 5.4%, a differential diagnosis was given, and in 17.6% there was no data.

From all discussed cases, 100 (8.5%) procedures were done. The average age was 70 years. Of the 26 procedures in patients without eventual lung cancer, the diagnosis prior to surgery was considered to be cancer in 69.2%, empyema in 19.2%, tuberculosis in 7.7% and lymphoma in 3.8%. Of these cases, histology showed metastatic disease with a non-lung primary in 23.1%.

Conclusion 

In our patient population a surgical procedure is performed in 37.7% of patients with lung cancer. This is higher than the surgical rate of 16.9% according to the audit criteria.
Apoptosis resistant bronchoalveolar lavage (BAL) fluid lymphocytes in sarcoidosis
Authors: H Stridh
Journal: Thorax (2002)

<b>Background:</b> Sarcoidosis is a chronic granulomatous lung disease of unknown origin. The accumulation of activated T cells at sites of inflammation represents an early stage in granuloma formation. Since mechanisms governing the normal resolution of inflammatory processes are poorly understood, this study aimed to investigate the apoptotic phenotype of peripheral blood and lung T lymphocytes from patients with sarcoidosis. <b>Methods:</b> Bronchoalveolar lavage (BAL) was performed in 10 patients with active sarcoidosis and five healthy controls. <b>Results:</b> Virtually no lymphocyte apoptosis, as determined by annexin V or Hoechst staining, was seen in either patients or controls. Sustained caspase-3 activity in non-apoptotic BAL fluid lymphocytes of the patients was detected, however, in agreement with in vitro studies demonstrating caspase activation after T cell receptor (TCR) triggering as a physiological response required for efficient T cell activation. Only 11.0% (range 7.7–17.6) of the BAL lymphocytes from sarcoidosis patients were annexin V positive after exposure to the apoptotic stimulus tributyltin compared with 55.0% (range 42.0–62.0) of BAL lymphocytes from healthy controls (p&lt;0.001). After anti-Fas treatment only 8.5% (range 6–10) of BAL fluid lymphocytes from patients but 45.5% (range 38–62) from healthy controls were apoptotic. <b>Conclusion:</b> BAL fluid lymphocytes from patients with sarcoidosis display a non-apoptotic morphology associated with endogenous caspase-3 activity. They seem to be resistant to apoptosis, which might contribute to the accumulation of inflammatory cells in the lungs, persistence of inflammation, and the development and maintenance of granuloma.
Combined Array-Comparative Genomic Hybridization and Single-Nucleotide Polymorphism-Loss of Heterozygosity Analysis Reveals Complex Changes and Multiple Forms of Chromosomal Instability in Colorectal Cancers
Authors: Michelle Gaasenbeek, Kimberley Howarth, Andrew J. Rowan, Patricia A. Gorman, Angela Jones, Tracy Chaplin, Ying Liu, David Bicknell, Eleanor J. Davison, Heike Fiegler, Nigel P. Carter, Rebecca R. Roylance, Ian P.M. Tomlinson
Journal: Cancer Research (2006)

Abstract Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid with multiple large-scale gains/deletions, but the processes underlying CIN are unclear and different types of CIN might exist. We investigated colorectal cancer cell lines using array-comparative genomic hybridization (CGH) for copy number changes and single-copy number polymorphism (SNP) microarrays for allelic loss (LOH). Many array-based CGH changes were not found by LOH because they did not cause true reduction-to-homozygosity. Conversely, many regions of SNP-LOH occurred in the absence of copy number change, comprising an average per cell line of 2 chromosomes with complete LOH; 1-2 terminal regions of LOH (mitotic recombination); and 1 interstitial region of LOH. SNP-LOH detected many novel changes, representing possible locations of uncharacterized tumor suppressor loci. Microsatellite unstable (MSI+) lines infrequently showed gains/deletions or whole-chromosome LOH, but their near-diploid karyotypes concealed mitotic recombination frequencies similar to those of MSI− lines. We analyzed p53 and chromosome 18q (SMAD4) in detail, including mutation screening. Almost all MSI− lines showed LOH and/or deletion of p53 and 18q; some near-triploid lines had acquired three independent changes at these loci. We found consistent results in primary colorectal cancers. Overall, the distributions of mitotic recombination and whole-chromosome LOH in the MSI− cell lines differed significantly from random, with some lines having much higher than expected levels of these changes. Moreover, lines with more LOH changes had significantly fewer copy number changes. These data suggest that CIN is not synonymous with copy number change and some cancers have a specific tendency to whole-chromosome deletion and regain or to mitotic recombination. (Cancer Res 2006; 66(7): 3471-9)
Quantitative evaluation of severity of behavioral and psychological symptoms of dementia in patients with vascular dementia
Authors: Wei-Dong Pan, Sohei Yoshida, Qian Liu, Chun-Lan Wu, Jun Wang, Jin Zhu, Ding-Fang Cai
Journal: Translational Neurodegeneration (2013)

Abstract To quantitatively evaluate severity of behavioral and psychological symptoms of dementia (BPSD) for vascular dementia (VD). Changes of 51 patients with VD in BPSD between the first and 24th week were assessed using the Neuropsychiatric Inventory (NPI) and the behavioral pathology in Alzheimer’s disease (BEHAVE-AD) rating scale, in detrended fluctuation analysis (DFA) represented by diurnal activity (DA), evening activity (EA), and nocturnal activity (NA), and the relationships were analyzed. The subscores of activity disturbances, diurnal rhythm disturbances, and anxieties and phobias in the BEHAVE-AD score, and that of agitation, irritability, and sleep disorder in the NPI score were significantly increased compared with the first week, as was for the changes for EA in the DFA value. A linear correlation was observed between the changes of activity disturbances plus anxieties and phobias, and those of DA, and between the development of diurnal rhythm and those of EA, the vehement and autism scores and those of DA, and the difference in sleep disorder scores and those of EA, respectively. Analysis of DA, NA, and EA may reflect the fluctuational degrees of VD-BPSD, can provide a useful assessment of VD-BPSD accompanied by clinical scores for VD.
Clinical Manifestations and Descriptive Epidemiology of Lyme Disease in New Jersey, 1978 to 1982
Authors: G. Stephen Bowen
Journal: JAMA (1984)

Clinical manifestations and epidemiologic characteristics of 117 cases (31 children and 86 adults) of Lyme disease in New Jersey from 1978 to 1982 are summarized. The male-female sex ratio was 1.9:1. An endemic focus in Monmouth County has been recognized. Erythema chronicum migrans was present in 93% of cases and was the only clinical manifestation in 25% of patients. Nonspecific febrile syndrome, in addition to erythema chronicum migrans, was present in 45% of cases; 26% had arthritis. The proportion of cases with arthritis in 1982 (7/56) was less than for 1978 to 1981 (24/61) probably because of better recognition of milder cases by physicians and earlier antibiotic treatment, which may have reduced late complications. Meningitis (10%) and cranial nerve palsies (8%) were the most frequent neurological manifestations. As medical personnel and the public become more aware of the disease, Lyme disease is being recognized with increased frequency in central and southern New Jersey.
Cell Cycle Regulators and Outcome of Adjuvant Cisplatin-Based Chemotherapy in Completely Resected Non–Small-Cell Lung Cancer: The International Adjuvant Lung Cancer Trial Biologic Program
Authors: Martin Filipits, Robert Pirker, Ariane Dunant, Sylvie Lantuejoul, Katharina Schmid, Anh Huynh, Vincent Haddad, Fabrice André, Rolf Stahel, Jean-Pierre Pignon, Jean-Charles Soria, Helmut H. Popper, Thierry Le Chevalier, Elisabeth Brambilla
Journal: Journal of Clinical Oncology (2007)

The International Adjuvant Lung Cancer Trial (IALT) demonstrated that adjuvant cisplatin-based chemotherapy improves the survival of patients with completely resected non-small-cell lung cancer (NSCLC). The purpose of our study was to determine whether cell cycle regulators are of prognostic and/or predictive value in patients who were enrolled onto the IALT.Expression of p27Kip1, p16INK4A, cyclin D1, cyclin D3, cyclin E, and Ki-67 was immunohistochemically assessed in tumor specimens obtained from 778 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic parameters.There was a relationship between p27Kip1 status and benefit of cisplatin-based chemotherapy (test for interaction, P = .02). Among patients with p27Kip1-negative tumors, cisplatin-based chemotherapy resulted in longer overall survival compared with controls (adjusted hazard ratio [HR] for death = 0.66; 95% CI, 0.50 to 0.88; P = .006). In patients with p27Kip1-positive tumors, overall survival was not different between patients treated with cisplatin-based chemotherapy and controls (adjusted HR for death = 1.09; 95% CI, 0.82 to 1.45; P = .54). The other cell cycle regulators and Ki-67 did not predict benefit of adjuvant cisplatin-based chemotherapy. None of these biomarkers was significantly associated with overall survival of the patients in the total study population.NSCLC patients with p27Kip1-negative tumors benefit from adjuvant cisplatin-based chemotherapy after complete tumor resection. Before establishing p27Kip1 as a routine marker for selection of patients for adjuvant chemotherapy, the predictive value of p27Kip1 has to be confirmed in patients from other trials.
Evolution of Structurally Disordered Proteins Promotes Neostructuralization
Authors: J. Siltberg-Liberles
Journal: Molecular Biology and Evolution (2010)

Protein structure is generally more conserved than sequence, but for regions that can adopt different structures in different environments, does this hold true?Understanding how structurally disordered regions evolve altered secondary structure element propensities as well as conformational flexibility among paralogs are fundamental questions for our understanding of protein structural evolution.We have investigated the evolutionary dynamics of structural disorder in protein families containing both orthologs and paralogs using phylogenetic tree reconstruction, protein structure disorder prediction, and secondary structure prediction in order to shed light upon these questions.Our results indicate that the extent and location of structurally disordered regions are not universally conserved.As structurally disordered regions often have high conformational flexibility, this is likely to have an effect on how protein structure evolves as spatially altered conformational flexibility can also change the secondary structure propensities for homologous regions in a protein family.
The prevention of biofilm colonization by multidrug-resistant pathogens that cause ventilator-associated pneumonia with antimicrobial-coated endotracheal tubes
Authors: Issam I. Raad, Jamal A. Mohamed, Ruth A. Reitzel, Ying Jiang, Tanya L. Dvorak, Mahmoud A. Ghannoum, Ray Y. Hachem, Anne-Marie Chaftari
Journal: Biomaterials (2011)
Genetic Dissection of Immunity to Mycobacteria: The Human Model
Authors: Jean-Laurent Casanova, Laurent Abel
Journal: Annual Review of Immunology (2002)

Humans are exposed to a variety of environmental mycobacteria (EM), and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. In addition, most of the world's population is occasionally exposed to human-borne mycobacterial species, which are less abundant but more virulent. Although rarely pathogenic, mildly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. Mycobacterium tuberculosis, M. leprae, and EM M. ulcerans are more virulent, causing tuberculosis, leprosy, and Buruli ulcer, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. The interindividual variability of clinical outcome is thought to result in part from variability in the human genes that control host defense. In this well-defined microbiological and clinical context, the principles of mouse immunology and the methods of human genetics can be combined to facilitate the genetic dissection of immunity to mycobacteria. The natural infections are unique to the human model, not being found in any of the animal models of experimental infection. We review current genetic knowledge concerning the simple and complex inheritance of predisposition to mycobacterial diseases in humans. Rare patients with Mendelian disorders have been found to be vulnerable to BCG, a few EM, and M. tuberculosis. Most cases of presumed Mendelian susceptibility to these and other mycobacterial species remain unexplained. In the general population leprosy and tuberculosis have been shown to be associated with certain human genetic polymorphisms and linked to certain chromosomal regions. The causal vulnerability genes themselves have yet to be identified and their pathogenic alleles immunologically validated. The studies carried out to date have been fruitful, initiating the genetic dissection of protective immunity against a variety of mycobacterial species in natural conditions of infection. The human model has potential uses beyond the study of mycobacterial infections and may well become a model of choice for the investigation of immunity to infectious agents.
Revalidation in sport and exercise medicine
Authors: D A D Macleod, M E Batt, S Sheard
Journal: British Journal of Sports Medicine (2002)

The proposed annual appraisal of practitioners of sport and exercise medicine is outlined

In 1999 the General Medical Council (GMC) of the United Kingdom agreed that “all doctors must be able to demonstrate regularly that they continue to be fit to practice in their chosen field”.1 This process is termed revalidation. Doctors who complete revalidation will be granted a “licence to practice”, affording them the rights and privileges currently associated with being included on the general register of the GMC.

Each individual doctor's revalidation will be reviewed every five years by two doctors and a single lay person. This team will be drawn from a local revalidation pool of trained people. Revalidation will be based on the contents of the individual doctor's revalidation portfolio. Each doctor's portfolio, irrespective of their specialty, will follow a standardised format. The relevant guidelines describing appropriate standards of practice will be drawn up by the Medical Royal Colleges. This immediately creates a challenge for sport and exercise medicine which does not have a single parent Medical Royal College and is not widely recognised as a specialty, although a small number of doctors have already been placed on the GMC specialist register.

The Intercollegiate Academic Board of Sport and Exercise Medicine (IABSEM) is responsible to its parent Medical Royal Colleges and Faculties for setting standards in sport and exercise medicine and would seem to be the appropriate body to draw up relevant guidelines to meet revalidation standards.

Doctors who are already Members or …
Hyperfiltration in remnant nephrons
Journal: Journal of the American Society of Nephrology (2001)

Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group II, nine rats that underwent right nephrectomy and segmental infarction of five-sixths of the left kidney and were fed a normal diet; and group III, seven rats that underwent the same renal ablative procedure and were fed a low protein diet. Single nephron glomerular filtration rate (SNGFR) was higher in the remnant kidney of group II rats compared with group I rats due to higher average values for mean glomerular transcapillary hydraulic pressure difference (delta P) and initial glomerular plasma flow rate (QA) in group II. Glomeruli in remnant kidneys of group II showed striking alterations in morphology, including epithelial cell protein reabsorption droplets, foot process fusion, and mesangial expansion. Group III rats demonstrated a mean SNGFR not statistically different from that of group I, but significantly less than that of group II rats. This lack of absolute hyperfiltration in remnant glomeruli of group III rats relative to group I obtained because QA and delta P did not increase above values found in group I. The glomerular structural lesions seen in group II were also largely attenuated in group III. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accompanied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive consequences by damaging remnant glomeruli.