tbuckley/cabot-search huggingface dataset:
Treatment of pulmonary carcinoid: Are there new options?
Authors: David Yabar, Susana Padrones, Raquel Pascual, Samantha Aso, Rosa López-Lisbona, Francisco Rivas, Jordi Dorca
Journal: European Respiratory Journal (2014)

INTRODUCTION  Pulmonary carcinoid represents 3% of lung neoplasms. Although surgical resection is the gold standard, endoscopic techniques may offer an alternative in selected cases.  METHODS  Retrospective study of all patients diagnosed with carcinoid tumor (1999-2013) at a terciary hospital. The epidemiology, clinical parameters, treatment type and overall survival were evaluated.  RESULTS  96 patients recruited. 63 had a smoking history>10 P-Y. Time from symptom onset to diagnosis: 13.69+/-11.64 months. Clinical features at presentation: recurrent pneumonia (n=36, 37.5%), cough (n=29, 30.2%), hemoptysis (n=16, 16.6%). 22 patients were asymptomatic (22.9%). The most common location: right upper lobe (n=24, 25%). Most frequent histology: typical type (n=81, 84.3%). 8 patients were managed conservatively.  3 tumor-related deaths: all with atypical histology and conservative treatment. Overall 5-year survival: 94.6%. For those treated endoscopically: 100%, for those receiving surgery: 97.8%.  CONCLUSIONS  Pulmonary carcinoid has generally a good prognosis. The treatment of choice is surgery, but in selected cases, endoscopic resection may be a good alternative, with comparable results to surgery.
Targeting Resistance in Egfr-Mutant Non-Small Cell Lung Cancer (Nsclc): Preclinical Evidence Supporting the Combination of Egfr Tyrosine Kinase Inhibitors (Tkis) Azd9291 and Gefitinib with Molecularly Targeted Agents and Immunotherapeutics
Authors: D. Cross, C. D'Cruz, C. Eberlein, P. Spitzler, E. Ichihara, C. Meador, S. Ashton, M. Mellor, R. Stewart, P. Smith, A. Schuller, M. Frigault, W. Pao, P.J. Jewsbury
Journal: Annals of Oncology (2014)
Nine Cases of Merkel Cell Tumour
Authors: Aniruddha Bose
Journal: Journal of the Royal Society of Medicine (1997)

Merkel cell tumour is an aggressive neuroendocrine neoplasm arising in the dermis. Although only a few hundred cases have been reported worldwide, nine were seen in Nottingham between 1985 and early 1994. The patients were five women and four men age 63-88. One was the first Afro-Caribbean reported to have such a tumour. In no case was the diagnosis made clinically; histological and histochemical examination was necessary. Three of the patients died quickly with metastatic disease. The primary treatment is surgical excision. For advanced disease, radiotherapy is commonly beneficial.
The similarity index and DNA fingerprinting.
Authors: M Lynch
Journal: Molecular Biology and Evolution (1990)

DNA-fingerprint similarity is being used increasingly to make inferences about levels of genetic variation within and between natural populations. It is shown that the similarity index--the average fraction of shared restriction fragments--provides upwardly biased estimates of population homozygosity but nearly unbiased estimates of the average identity-in-state for random pairs of individuals. A method is suggested for partitioning the DNA-fingerprint dissimilarity into within- and between-population components. Some simple expressions are given for the sampling variances of these estimators.
Cardiovascular Manifestations of HIV Infection
Authors: Giuseppe Barbaro
Journal: Journal of the Royal Society of Medicine (2001)

Studies published over the past three years have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac illness in both children and adults1 (Table 1). This recent work shows that subclinical echocardiographic abnormalities independently predict adverse outcomes and identify high-risk groups who can then be targeted for early intervention and therapy2.



Table 1

HIV-associated cardiovascular abnormalities



The introduction of highly active antiretroviral therapy (HAART) regimens has greatly modified the course of HIV disease, with longer survival and better quality of life; however, early data from those treated raise concerns about a possible increase in both peripheral and coronary arterial diseases. In global terms HAART is available only to a minority of HIV-infected individuals, and studies before the advent of HAART remain applicable. UNAIDS estimates that 36.1 million people were living with HIV infection at the end of the year 20003. If 9-10% of patients develop symptomatic heart failure over 2-5 years4, then 3 million cases of HIV-related heart failure will present in that time period5. In this review article, I discuss the principal HIV-associated cardiovascular manifestations, with an emphasis on new knowledge about prevalence, pathogenesis and treatment.
Regulation of IKKe expression by androgen receptor and NF-kB transcriptional factor in prostate cancer
Authors: B. Péant, J. Diallo, L. Lessard, A. Mes-Masson, F. Saad
Journal: Journal of Clinical Oncology (2006)

10106 Background: In unstimulated cells, NF-kB transcription factor is sequestered in the cytoplasm as an inactive p65/p50 dimer through interaction with a member of the inhibitor of kB protein family (IkBa). Prominent constitutive activation of NF-kB was observed in prostate cancer (PCa) cell lines lacking androgen receptor (AR) expression (PC3 and DU145) whereas only very low levels of NF-kB activity were seen in androgen-dependent cell lines (LNCaP and CWR22Rv1). As IkB kinase-e (IKKe) has recently been shown to be controlled by NF-kB, we hypothesize that IKKe may be involved in PCa progression based on its interaction with the NF-kB protein, and that these interactions are influenced by AR signaling. Methods: LNCaP cells were used to study IKKe expression with or without stimulation by the analog of androgen R1881 and by the tumor necrosis factor (TNF)-a. IKKe protein and RNA expression were characterized by immunoblot assay and quantitative PCR, respectively. IKKe expression was then correlated with p65 nuclear localisation. NF-kB activity was inhibited using an IkBa dominant negative construction. Inhibition of AR synthesis was performed using a siRNA against AR. Results: IKKe gene expression was stimulated by TNF-a treatment in LNCaP cells and inhibited by transfection of a dominant negative form of IkBa which prevented the nuclear translocation of p65. We also observed constitutive IKKe expression in hormone-refractory cells. Furthermore, we showed that TNF-a-induced IKKe expression is inhibited by R1881 in hormone-responsive PCa cells and this inhibition was correlated with the modulation of IkBa expression by R1881. Finally, we observed that the expression of IKKe is constitutively induced after blocking AR expression in LNCaP cells. Conclusions:. Our results show that IKKe expression is regulated by NF-kB in PCa cell lines. Moreover, IKKe appears to be down-regulated by ligand-dependent AR signaling through the control of IkBa expression. Further studies will be needed in order to determine the implications of this phenomenon with regard to NF-kB regulation, androgen resistance and effect on PCa progression. No significant financial relationships to disclose.
Lung volumes measured by the forced rebreathing technique in children with airways obstruction
Authors: PJ Merkus, S Verver, EE van Essen-Zandvliet, EJ Duiverman, KF Kerrebijn, PH Quanjer
Journal: European Respiratory Journal (1992)

Forced rebreathings may recruit trapped gas into the mixing process. Therefore, we assessed the validity and reproducibility of measurements of residual volume (RVN2) by forced rebreathing in a closed circuit using N2 as indicator gas (N2FR) in children with airways obstruction. Validity was studied from measurements of RV obtained by N2FR, by helium dilution during resting ventilation, and by body plethysmograph at low panting frequency in young patients (8-18 yrs, 13 with asthma, forced expiratory volume in one second (FEV1) 93.0 +/- 22.8% pred; 12 with cystic fibrosis (CF), FEV1 80.4 +/- 16.4% pred). Reproducibility of RVN2 was assessed from duplicate measurements in 73 patients with asthma before and after bronchodilation (FEV1 81.4 +/- 13.7 and 99.6 +/- 11.5% pred, respectively), and in nine patients with CF; the total lung capacity (TLC) was unaffected by bronchodilation; 3,797 +/- 830 ml and 3,807 +/- 843 ml, respectively. Gas dilution methods gave comparable results in all subjects but gave lower values than plethysmography in patients with cystic fibrosis. Reproducibility was satisfactory, median differences between duplicate measurements of RVN2 and TLCN2 varying between 13 and 46 ml, respectively. We conclude that N2FR is quickly performed and well-tolerated. Lung volumes are highly reproducible and agree well with those obtained with the helium dilution method. Deep inspirations do not seem to overcome gas trapping in patients with CF.
The VCD-5: A short questionnaire for the diagnosis of vocal cord dysfunction
Authors: Andrew Thurston, Jemma Haines, Brigit Chesworth, Siobhan Lillie, Stephen J. Fowler
Journal: European Respiratory Journal (2013)

Background: Vocal Cord Dysfunction (VCD) typically involves abnormal adduction of the vocal cords during inspiration, potentially mimicking the symptoms of asthma and leading to increased prescription of ineffective medications. We aimed to develop a clinical tool for identifying VCD in patients with breathlessness, by simplifying our previously developed questionnaire (VCDQ).

Method: The VCDQ comprises items focusing on specific symptoms common to VCD. A 5-point Likert scale is used, and it has been validated in VCD patients and healthy controls. Thirty-one patients with endoscopically confirmed VCD (approximately half also had asthma), 29 asthmatics with no history of VCD, and 14 healthy controls were recruited to complete the 12 item VCDQ. We ranked the questions by discriminatory power and selected the best-performing to form a new short questionnaire

Results: The sum of scores from all 12 questions classified VCD versus healthy (Mann-Whitney test: z = -5.390, P < 0.001) and asthma (z = -5.730, p < 0.001). For VCD versus asthma question-specific z-scores ranged from –0.809 to –5.744. Five questions had z-scores <-4.80 with p< 0.001, and using these alone improved classification between groups (area under receiver operating characteristics curve 0.988, compared to 0.953 with all 12 items). Using a cut-off score of 16/25, the short questionnaire had a sensitivity of 97% and specificity of 94% for VCD.

Conclusion: Our five-item VCDQ is effective in differentiating VCD from asthma and, with prospective testing in new cohorts, may become a useful tool to identify patients with potential VCD for referral to specialist clinics for definitive diagnosis and treatment.
Prognostic Value of Coronary CTA in Coronary Bypass Patients
Authors: Saima Mushtaq, Daniele Andreini, Gianluca Pontone, Erika Bertella, Antonio L. Bartorelli, Edoardo Conte, Andrea Baggiano, Andrea Annoni, Alberto Formenti, Daniela Trabattoni, Fabrizio Veglia, Francesco Alamanni, Cesare Fiorentini, Mauro Pepi
Journal: JACC. Cardiovascular imaging (2014)
Pharmacokinetics of drugs for non tuberculous mycobacterial lung infections
Authors: Cecile Magis-Escurra, Jakko van Ingen, Rob Aarnoutse
Journal: European Respiratory Journal (2012)

Successful treatment for Non-Tuberculous Mycobacterial (NTM) infections is easily frustrated. Little is known about the pharmacokinetics (PK) and dynamics of treatment regimens in relation to treatment outcome. Drug concentrations may be an intermedian link. In NTM disease very few PK studies have been performed. We performed a prospective, descriptive pharmacokinetic (PK) study of the plasma pharmacokinetics (full PK-curve) of rifampicin (RIF), ethambutol, clarithromycin, azithromycin, isoniazid and moxifloxacin and their active metabolites in a Dutch series of patients with clinically relevant NTM lungdisease and we compared the results with two other series from the literature. The baseline characteristics are shown in table 1.

View this table:

baseline characteristics





Table 2 shows the main PK results.

View this table:

main pharmacokinetic parameters





Results were generally consistent with the data published in the past by Wallace and Peloquin. Our data showed that rifampicin causes a reduction in clarithromycin and azithromycin serum concentrations. The current study has confirmed the significant PK interactions between rifampicin and clarithromycin and we feel this calls for a reevaluation of the dosing strategies in NTM lung disease as an inadequate response to treatment might be attributed to suboptimal drug exposure.
Sleep disordered breathing (SDB) at age 5 in a cohort of very preterm (VP) children and controls
Authors: Claudia Calogero, Livia Drovandi, Monica Da Frè, Enrico Lombardi, Fabio Voller, Franca Rusconi
Journal: European Respiratory Journal (2013)

Available data on SDB in former prematurely born children are scarce.

All infants born at 22-31 wks gestational age (GA) (Tuscany, Italy, July ’03-June ’04) were followed up to 5-6 yrs. Their parents and those of a control group (matched by age, sex, and residence area) filled in a questionnaire on respiratory health. Data were available for 188 cases on 239 and 362 controls. In addition, we obtained data also on 48 ex-preterm <28 wks GA born July ’04-June ’05.

Frequencies of snoring when asleep and mouth breathing when awake, defined as: never, occasional (< once/week), frequent (1-4 times/week), and constant (5-7 times/week), in 188 VP and 362 controls were as follows:

View this table:



In VP children, frequent or constant “stop breathing during sleep” and “difficulty breathing when asleep” were very rare (2%).

Considering both groups of VP: 10 children had already undergone adenoidectomy. After adjusting for sex, risk factors for frequent or constant snoring or adenoidectomy: GA < 25 wks (OR: 2.3; 95% CI: 1.0; 5.1) and smoke exposure in utero or in the first year of life (OR: 2.3; 95% CI: 1.0; 4.9).

In conclusion, being born VP is associated with a higher risk of habitual snoring and mouth breathing up to 5-6 years; this could be relevant for both growth and neurocognitive impairment. The reason why extremely low GA and maternal smoking exposure increase habitual snoring still needs to be elucidated.
A retrospective analysis of methotrexate therapy as a steroid sparing agent within a UK severe asthma clinic
Authors: Leanne Jo Holmes, Helen C. Francis, Robert M. Niven
Journal: European Respiratory Journal (2012)

Background.  Treatment with Methotrexate (MTX) immunosupressive therapy in severe asthma is used in an effort to reduce corticosteroid dependancy and associated side effects. This study aimed to evaluate the effectiveness of MTX within this patient population as an efficient aid to reduce corticosteroids.  Methods  A retrospective data collection was performed within the severe asthma service. Patients whom were established on or had started MTX within the last twelve months were included. Variables explored included mean daily corticosteroid dose, exacerbation frequency, acute admission episodes and blood eosinophil count twelve months prior to and twelve months post commencement of Methotrexate therapy.  Results  n= 30, 9 patients stopped MTX due to side effects. Within the ongoing sample group, corticosteroid dose was significanlty lower post MTX compared to previous treatment (mean dose 10.4mg daily post MTX compared with 16.8mg pre MTX [p  Conclusion  MTX (where tolerated within this severe asthma population) was found to significantly reduce the demand for corticosteroids. A reduction in exacerbation rate and hospitalisation are also demonstrated when sufficiently monitored and supervised within a specialist setting.
A doctor’s dilemma: choices amidst change
Authors: P. Frederick Sparling
Journal: Journal of Clinical Investigation (2015)

It is a great privilege to deliver the Kober Lecture, which honors the many contributions of the former dean of Georgetown Medical School. George Kober, a contemporary of William Osler, was a leader in infectious diseases and public health and medical education. The nomination was quite a surprise, since the list of the 30 previous lecturers includes at least three Nobel Prize winners and 22 members of the National Academy of Sciences. I am deeply indebted to the Association of American Physicians for honoring me in this way. In considering this address, many ideas occurred; the best was to demonstrate how an ordinary physician-scientist, measured by the standards of our combined societies, can succeed in academic medicine.
Specific Targeting, Biodistribution, and Lack of Immunogenicity of Chimeric Anti-GD3 Monoclonal Antibody KM871 in Patients With Metastatic Melanoma: Results of a Phase I Trial
Authors: Andrew M. Scott, Fook-Thean Lee, Wendie Hopkins, Jonathan S. Cebon, Jennifer M. Wheatley, Zhanqi Liu, Fiona E. Smyth, Carmel Murone, Susan Sturrock, Duncan MacGregor, Nobuo Hanai, Kengo Inoue, Motoo Yamasaki, Martin W. Brechbiel, Ian D. Davis, Roger Murphy, Anthony Hannah, Michael Lim-Joon, Tony Chan, Geoffrey Chong, Gerd Ritter, Eric W. Hoffman, Antony W. Burgess, Lloyd J. Old
Journal: Journal of Clinical Oncology (2001)

KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma.Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10.Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period.This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.
Prediction of chronic renal failure in patients with chronic obstructive pulmonary disease
Authors: Sawsan Elsawy, Samiha Abu Bakr, Sabah Oraby, Taghreed Saied, Omima Abu Elkhair
Journal: European Respiratory Journal (2014)

Background: Chronic renal failure (CRF) rises in prevalence with age and is frequently associated with chronic diseases such as congestive heart failure and diabetes mellitus (DM). It is unknown to which extent COPD is associated with CRF and the relationship between CRF and COPD is undescribed

Rational: CRF may be associated with normal serum creatinine, a condition known as unrecognized or concealed CRF. It is diagnosed by glomerular filtration rate (GFR) < 60 mL/min/1.73 m2.

Objectives: To investigate the prevalence and correlation of both concealed and overt CRF in patients with COPD.

Methods: We measured the GFR for 527 subjects their ages ranged from 38- 78 years (327 COPD patients and 200 diabetic patient) using the Modification of Diet in Renal Disease (MDRD) Study Group equation

Measurements and Main Results: The main finding is the high prevalence of CRF (concealed and overt) among patients with COPD. As 66/327 of all COPD patients have CRF despite more or less accepted serum creatinine .The prevalence of normal and reduced GFR in COPD group were 80.1 % and 19.9%, while in COPD group with either DM or hypertention (HTN) it was 75.45 and 24.6%. The corresponding prevalence in DM group was 88% and 12%. Moreover, In COPD group 17.55% (46/262) had concealed renal failure (RF), while 1.52 % (4/262) had overt RF. In COPD with DM or HTN 18.46 % (12/65) had concealed RF, while 6.15% (4/65) had overt RF. While in DM group 10 % (20/200) had concealed RF, while 2% (4/200) had overt RF.

Conclusions: our data support that CRF either concealed or overt are prevalent among COPD patients than among DM, this prevalence is further increased in COPD patients with other co morbidities.
Influence of Age on Induction With Urethan of Hepatomas and Other Tumors in Infant Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Michael Klein
Journal: JNCI Journal of the National Cancer Institute (1966)

Suckling 86AF1/J hybrid mice were treated once by stomach tube with urethan at 1 week of age. Some of these hybrids received subsequent repeated treatment beginning at 4 weeks; others were treated once only with the same carcinogen on a body-weight basis and on day 1 to day 28 postpartum. Treatment of 1-week-old hybrids once with urethan resulted in the development of hepatomas in 33 percent of the males and in none of the females. When the same treatment was followed 3 weeks later by 15 additional treatments with urethan, large numbers of pulmonary adenomas developed. However, the incidence of hepatomas remained unchanged in both sexes. The liver showed a greater tumorigenic response to urethan than any other organ except the lung. Both age of suckling mouse at time of treatment with urethan and sex inAuenced liver tumorigenesis. Tumor yield was consistently greater for the males than for the females in each age group. Based on tumor yield, a peak response was observed for mice of both sexes treated on day 7. Also, the yield of hepatomas decreased more slowly for males than for females after day 7 and reached control levels on day 28 for the males and on day 21 for the females. Lung tumorigenesis, in contrast to liver tumorigenesis, was not influenced by age of suckling mouse at time of treatment and sex. Harderian gland adenomas and forestomach papillomas also were observed among experimental mice, the data suggesting that their induction may have been enhanced by treatment with urethan. The utilization of immature mice in bioassay testing procedures for potential carcinogens is discussed.