tbuckley/cabot-search huggingface dataset:
Spirometric standards for healthy adult lifetime nonsmokers in Australia
Authors: C J Gore, A J Crockett, D G Pederson, M L Booth, A Bauman, N Owen
Journal: European Respiratory Journal (1995)

The aim of this study was to develop suitable spirometric prediction equations for asymptomatic Caucasian adults in the Australian population. These equations were compared with those of previous studies and constants were presented which, when associated with the prediction equations, permitted the calculation of 5% tolerance intervals for lung function. The 1,302 subjects (aged 18-78 yrs) who underwent pneumotachograph spirometry, using techniques recommended by the American Thoracic Society, were a sample from metropolitan Adelaide, South Australia. The variables recorded were sex, age, height, mass, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), forced mid-expiratory flow (FEF25-75%) and FEV1/FVC ratio. Complete data were obtained for 614 females and 621 males, but the sample was reduced to 249 females and 165 males when only lifetime nonsmokers with no adverse bronchial symptoms were selected. Prediction equations of normal lung function were obtained from the reduced sample by multiple regression, with age, height and functions of both age and height as predictors. The derived equations did not differ significantly from the majority of previously reported equations and were generally superior in their ability to predict the lung function of the asymptomatic ex-smokers who were part of the original sample. Analysis of the sensitivity, specificity and predictive power of 5% tolerance limits for the presence of symptoms revealed the important roles of FEV1, FEV1/FVC and FEF25-75% in diagnostic testing. The present prediction equations are recommended for use on the Australian population and on populations with similar Caucasian characteristics.
Parabiosis of CBA Parental and (CBA-T6T6 × C57BL)F&lt;sub&gt;1&lt;/sub&gt; Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. Jurin, N. Allegretti
Journal: JNCI Journal of the National Cancer Institute (1970)

This investigation explored the effect of altering the immunological reactivity of parental CBA mice before parabiosis with (CBA-T6T6 × C57BL)F1 hybrids. In 90% of the pairs the hybrids died first when they were joined to untreated CBA mice, but in 10% both mice died. Hybrids dying of parabiotic disease showed a decreased body weight, transient anemia, a lowered peripheral mononuclear leukocyte count, reduced splenic weight and cellularity, an increased incidence of parental cells in mitosis in the spleen, and lymphoid tissue atrophy. CBA partners had transient polycythemia, a lowered peripheral mononuclear leukocyte count, an increased splenic weight and cellularity, and few hybrid cells in mitosis in the spleen. Over 70% of the midlethally irradiated CBA parabionts died first when joined to F1 hybrids, and showed signs of parabiotic (allogeneic) disease. The lethally irradiated CBA mice were protected from death by parabiosis with hybrids. Nonspecific presensitization of CBA mice with Bacillus Calmette-Guérin or specific sensitization by C57BL skin allograft caused earlier death of hybrid parabionts. Both specifically presensitized and midlethally irradiated CBA parabionts had marked lymphoid atrophy. Pink-stained material resembling amyloid surrounded atrophic lymphatic follicles.
Evaluation of lung biopsy techniques for diagnosis of idiopathic interstitial pneumonias
Authors: Nitin Abhyankar, Jayshree Jain, Ajit Tambolkar
Journal: European Respiratory Journal (2011)

Aim: To assess and compare efficacy and safety of medical thoracoscopic lung biopsy with transbronchial lung biopsy (TBLB) for diagnosis of idiopathic interstitial pneumonias.

Material and methods: 59 patients with restriction on spirometry (Mean FVC -1.41 litres), exertional dyspnoea and interstitial pattern on HRCT (non classical for UIP) underwent lung biopsy using medical thoracoscopy.31 patients with comparable clinical profiles subjected to bronchoscopy and TBLB were used as controls.

Results: (Study group) Overall diagnostic yield was 98.3%. UIP (59.3%) was most frequent histopathological pattern.There were no intraoperative or immediate postoperative complications.Eventual complications included (in 19 patients) air leaks and prolonged ICD drainage (10), Delayed wound healing (3) and need for ventilatilatory support (5). Average duration of ICD was 4.81 days and average length of hospital stay was 6 days.There were 5 deaths within 1 month of the procedure (1 attributed to ischemic heart disease and Left ventricular failure,two to nosocomial pneumonia, two to unknown cause post discharge). Prolonged prior steroid use was single important factor associated with increased incidence of complications (14/23 complications in patients steroids vs. 5/36 complications in patients off steroids) (p<0.05).In the control group conclusive diagnosis was reached in 3/31 cases (1Sarcoidosis,1 DIP,1 BOOP). Pneumothorax needing intercostal drainage was encountered in 2 cases.

Conclusions: 1. Medical thoracoscopic Lung biopsy has higher diagnostic yield than TBLB. (98.1% vs 9.7%) (p<0.0001). 2. Prolonged prior steroid use is associated with increased incidence of complications (p<0.05).
Gender difference in the relationship between serum periostin and the indices of flow volume curve, and serum IgE
Authors: Hiroshi Odajima, Kenji Izuhara, Junya Ono
Journal: European Respiratory Journal (2014)

Background; Serum periostin (periostin) is one of the markers of allergic inflammation. However these is a few report about the relationship between the serum periostin level and the severity of asthmatic symptoms in children or airway narrowing.We reported that it was correlated the severity of childhood asthma and the indices of flow-volume curve(F-Vc). In allergic diseases, there are gender differences in the prevalence and clinical symptoms, etc.  Aim; The aim of this study is to clarify the gender difference among periostin and indices of F-Vc, and serum IgE.  Subjects and methods; In 2013, children, aged 6-12yo, from 6 elementary schools were diagnosed to be able to be recruited for this study because they satisfied the criteria of ISAAC questionnaire. Gender differences were studied in the relationship between periostin and indices of F-Vc, serum IgE, mite specific IgE, and Japanese cedar (JC) specific IgE. We divided the subjects into two groups due to the age, 6∼9 age(G1) and 10∼12 age(G2).  Results; In the G1, periostin was significantly related, in female to indices of F-Vc, and serum IgE in male. In the G2, there was only a significant relationship between periostin and specific IgE for mite.  Discussion ; In the male asthmatic children, the airway narrowing is more related to the allergic inflammation evaluated by periostin, and to serum IgE, compared to the female children.  However, after the puberty, the airway narrowing might be not related to the allergic inflammation evaluated by such as periostin, and serum IgE, but related only to the mite-specific IgE. It may be important findings to treatment the childhood asthma.
Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant.
Authors: R Little, R E Wittes, D L Longo, W H Wilson
Journal: Journal of Clinical Oncology (1998)

PURPOSE Bone marrow transplant (BMT) can cure recurrent Hodgkin's disease, but more than half of patients will progress and require additional treatment. When this occurs, there are no curative options and palliative therapy is usually indicated. In such patients, we have routinely used long-term vinblastine therapy because of its relatively low toxicity and high activity. PATIENTS AND METHODS We retrospectively reviewed the charts of all patients with Hodgkin's disease who relapsed after autologous BMT since 1991. Of 23 patients, 16 received vinblastine; we also include our index case, who began vinblastine following relapse in 1987. Patients received vinblastine 4 to 6 mg/m2 every 1 to 2 weeks, and continued until evidence of disease progression. RESULTS The 17 patients in this report had a median age of 31 years, performance status of 2, had received a median of three prior regimens, and 12 (71%) patients were advanced stage. Ten (59%) patients had objective responses, of which two (12%) were complete (CR) and eight (47%) were partial (PR). Two additional patients without measurable disease clinically improved for more than 6 months, and 1 patient had stable disease for more than 18 months. With a median follow-up of 20.4 months, the median event-free (EFS) and overall survival were 8.3 and 38.8 months, respectively. The two complete responders remain in remission at 4.6+ and 9+ years. Vinblastine was well tolerated with 3% of cycles associated with fever and neutropenia, and no cumulative or chronic toxicity. CONCLUSION Vinblastine provides effective palliation with low toxicity in recurrent Hodgkin's disease following transplant. These results suggest that long-term vinblastine therapy may be potentially curative and should be considered as initial therapy for such patients.
Modification and Implementation of NCCN Guidelines™ on Non–Small Cell Lung Cancer in the Middle East and North Africa Region
Authors: Abdul-Rahman Jazieh, Hanaa Bamefleh, Ahmet Demirkazik, Rabab Mohamed Gaafar, Fady B. Geara, Mansur Javaid, Jamal Khader, Kian Khodadad, Walid Omar, Ahmed Saadeddin, Hassan Al Sabe, Mohammad Behgam Shadmehr, Amgad El Sherif, Najam Uddin, Mohammad Jahanzeb, David Ettinger
Journal: Journal of the National Comprehensive Cancer Network (2010)

A lung cancer committee from the Middle East and North Africa (MENA) region was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Non-Small Cell Lung Cancer to create a platform for standard care in the region. The committee comprised different experts in thoracic oncology from the region, including the disciplines of medical and clinical oncology, radiation oncology, thoracic surgery, pulmonary medicine, radiology, and pathology. The committee reviewed version 2 of the 2009 NCCN Guidelines on Non-Small Cell Lung Cancer and identified recommendations requiring modification for the region using published evidence and relevant experience. These suggested modifications were discussed among the group and with a United States-based NCCN expert for approval. The recommended modifications, with justification and references, were categorized based on the NCCN Guidelines flow. This article describes these recommended modifications. The process of adapting the first NCCN-based guidelines in the region is a step toward helping to improve lung cancer care in the region and encouraging networking and collaboration.
The role of nerve transplantation in the management of symptomatic diaphragm paralysis
Authors: Matthew Kaufman, Andrew Elkwood, Michael Rose, Tushar Patel, Russell Ashinoff
Journal: European Respiratory Journal (2012)

Diaphragm paralysis may cause symptomatic respiratory disturbances, and often occurs as a result of iatrogenic or traumatic phrenic nerve injury. Treatment options have been limited to plication of the diaphragm, however it is likely that most patients receive no therapeutic intervention regardless of the severity of symptoms. Although nerve transplantation is efficacious for various peripheral nerve injuries, it has only begun to be established for analogous conditions involving the phrenic nerve.  Thirty consecutive patients presenting with chronic, symptomatic phrenic nerve injuries following surgery, chiropractic manipulation, trauma or anesthetic blocks underwent a comprehensive evaluation, including radiographic and electrophysiologic assessments. Inclusion criteria consisted of patients who failed to improve during six months of conservative management, in whom a clear etiology for phrenic nerve injury could be elicited and confirmed with pre-operative evaluation. Measures of post-operative improvement included: pulmonary function testing, chest fluoroscopy, and a standardized quality-of-life survey.  Reversal of diaphragm paralysis was clearly demonstrated in 77% of patients (23/30) following nerve transplantation. In four patients (13%) there was no clinical or radiographic evidence of diaphragm function after 18 months, whereas in the remaining three patients (10%) it was too early to determine if surgical intervention was successful. There were no pulmonary or cardiac complications.  Nerve transplantation may reverse phrenic nerve injury and should be considered as an effective treatment option in the management of symptomatic diaphragm paralysis.
Radiolabeled Antitumor Antibodies. III. Highly Iodinated and Highly Radioiodinated Antibodies2
Authors: S. Nord, I. L. Weissman
Journal: JNCI Journal of the National Cancer Institute (1974)

Antitumor antibodies could be iodinated and radioiodinated, and five-sixths (at 2 moles I/mole IgG) to one-third (at 21 moles I/mole IgG) of their antigen-binding activity could be retained, depending on the degree of iodination. Specific antibody inactivation by iodination involved denaturation of protein with increasing levels of iodination, presumably by a change in the charge structure and autoalteration of radioiodinated immunoglobulin as a result of radioactive decay. The first mode of inactivation increased the nonspecific binding of rat immunoglobulin to Moloney lymphoma cells (LSTRA) with higher levels of iodination, whereas it decreased the antibody-specific binding. In vivo absorption of these highly iodinated antibodies led to a selective loss of the subpopulation of iodinated anti-Moloney immunoglobulins which nonspecifically bind to LSTRA cells.
The role of MKK3 in allergic and non-allergic inflammatory responses in the lung
Authors: Tatjana Holand, Yanira Riffo-Vasquez, Domenico Spina, Brian O'Connor, Francis Woisin, Mike Marber, Kevin Bacon, Christian Rolff
Journal: European Respiratory Journal (2011)

MKK3 is a member of the p38 MAPK signaling pathway and is an important factor in non allergic inflammatory and Th1 responses. Less is known about the role of MKK3 in allergic inflammation. We investigated the role of MKK3 in murine models of non-allergic and allergic lung inflammation. Wild Type (WT) mice were instillated with lipopolysaccharide (LPS) (10 μg, i.t) or zymosan (100μg i.t.). A significant increase in neutrophil numbers in the lung were observed 24h later compared to saline controls (saline: 0.3±0.01  vs  LPS: 9.4±1.9; zymosan: 6.2±0.8×10 5 /ml, n=9. p≤0.05) or MKK3 -/-  KO mice (LPS: 0.36±0.04; zymosan: 0.57±0.3×10 5 /ml, n=10). WT mice also produced significant levels of IL-6, IL-12, TNF-α and INF-α as compared to saline mice. MKK3 -/-  mice did not release these cytokine in response to LPS or zymosan. WT mice were sensitized twice to ovalbumin (ova, 10mg/mouse i.p in alum). From day 14 all mice were exposed to 3% ova once daily for 3 days. Lung lavages were performed 24 h after the last exposure. Exposure to ova significantly increased eosinophils number in the lungs of ova-sensitized mice as compared with sham-immunized mice (sham: 0±0  vs  ova WT: 0.45±0.11, n=11; ova MKK3 -/- : 2.83±0.74, n=13×10 5 /ml). Ova-MKK3 -/-  mice showed significant increase of IL-5 compared to WT ova and sham-immunized mice (sham: 0.38±0.98 vs ova WT: 3.5±1.9 and ova MKK3 -/- : 20.8±10.7 pg/ml). MKK3 -/-  mice showed significantly higher levels of IgE compared to WT mice, irrespective of ova treatment (sham WT: 0±0; ova WT: 6062.3±560 pg/ml, n=6; sham MKK3 -/- : 4414.5±637, ova MKK3 -/- : 5328.8±415.8 pg/ml, n=13). In conclusion, MKK3 differentially regulates allergic and non-allergic responses in the lung.
Belgian prospective, multicenter, observational study of patients with malignant pleural mesothelioma treated with pemetrexed plus platinum
Authors: Kristiaan Nackaerts, Marc Lambrechts, Frederique Bustin, Luc Van Zandweghe, Benoît Colinet, Michiel Thomeer, Jean François Rosier, Kees Kraaij, Yulia D'yachkova
Journal: European Respiratory Journal (2014)

Introduction  Pemetrexed (pem) + cisplatin (cis) is the only chemotherapy regimen with marketing authorization for treating chemonaive patients (pts) with unresectable malignant pleural mesothelioma (MPM).  Aims and objectives  The study collected pt characteristics and survival data related to pem use at request of Belgian authorities.  Methods  Study of pts with unresectable MPM starting 1st-line treatment (tx) with pem+cis. Authorities set sample size (n=100). Analyses used standard descriptive summaries and Kaplan-Meier method for survival.  Results  111 pts receiving ≥1 dose of pem were observed from Aug 2006 to Nov 2012. Median duration of follow-up was 14.7 months; pts treated for median 4.6 months (6 cycles; maximum 44 cycles). Overall, 29 pts (26.1%) received carboplatin not cis: 7 at 1st cycle and 22 later. Other results are in the table. Tx was discontinued for completion of planned cycles with partial response/stable disease (36.0%), disease progression (28.8%) and adverse event/toxicity (21.6%). By study end, 96 pts (86.5%) had died, 10 (9.0%) were lost to follow-up and 5 (4.5%) were alive and censored.  Conclusions  Pem was used in accordance with its label in the majority of pts who received platinum-pem 1st-line tx for unresectable MPM in routine practice.
PWE-030 Sigmoidoscopy both delays time to diagnosis and has poor diagnostic utility for paediatric-onset inflammatory bowel disease
Authors: R J Dart, R K Russell, J R Read, P Rogers, P M Gillett, D C Wilson
Journal: Gut (2010)

<h3>Introduction</h3> A significant proportion of inflammatory bowel disease (IBD) presents in childhood and adolescence, a critical time for growth and development, so timely diagnosis is desirable to ensure patients achieve their growth potential. Our aim was to delineate factors including referral pathway and endoscopic investigation that may delay diagnosis in paediatric-onset IBD (PIBD). <h3>Methods</h3> We performed a retrospective case note review in a tertiary PIBD centre from 1996–09. Symptom onset was defined as the length of history of presenting complaint; date of presentation was defined as the first presentation, often to primary care. Date of each referral, to whom, and the investigations carried out by each discipline before either diagnosis or onward referral were recorded. Date of diagnosis is defined as the date of the endoscopy providing definitive histological diagnosis. Statistical analysis was performed with Excel. <h3>Result</h3> 166 PIBD patients with a median (range) age at diagnosis of 11.5 (2–17) years: 58% had Crohn9s disease, 24% had ulcerative colitis and 18% had indeterminate colitis. Median time from first symptoms to diagnosis was 27.5 weeks (2–445) and from first referral to diagnosis was 14 (0–439) weeks. Median (range) time to diagnosis from referral was faster when first referral was made to medical paediatrics in contrast to surgical services at 11 (0–341) vs 33 (0–439) weeks (p=0.001). 23% of patients underwent sigmoidoscopy prior to diagnosis, 12% colonoscopy alone and 67% colonoscopy+upper GI endoscopy (UGIE). 76% of sigmoidoscopies, performed in isolation, were performed by surgeons, whereas 97% of colonoscopy+UGIE were performed by paediatric GI services; sigmoidoscopy diagnosed IBD on 55% of occasions whereas colonoscopy+UGIE diagnosed IBD on 99% of occasions (p=0.0001). Colonoscopy alone was diagnostic on 80% of occasions, inferior to colonoscopy and UGIE (p=0.002). Median time to PIBD diagnosis when sigmoidoscopy was performed prior to diagnosis was significantly longer than for patients who had no sigmoidoscopy performed, at 29.5 (1–402) vs 12 (0–439) weeks (p=0.005). <h3>Conclusion</h3> Use of sigmoidoscopy as opposed to colonoscopy+UGIE was associated with delayed PIBD diagnosis. We suggest that sigmoidoscopy should be abandoned in the diagnosis of PIBD, and Colonoscopy and UGIE is the endoscopic investigation of choice, supporting the “Porto criteria” for PIBD diagnosis.<sup>1</sup>
Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden.
Authors: O T Jóhannsson, J Ranstam, A Borg, H Olsson
Journal: Journal of Clinical Oncology (1998)

PURPOSE Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.
Anti-oxidants modulate protein phosphatase 2A (PP2A) activity to counteract cigarette smoke generated reactive oxygen species
Authors: Patrick Geraghty, Andrew Hardigan, Sonya Gadhvi, Alison Wallace, Oleg Mirochnitchenko, Jincy Thankachen, Leo Arellanos, Victor Thompson, Tina Zelonina, Jeanine D'Armiento, Robert Foronjy
Journal: European Respiratory Journal (2012)

Introduction

Phosphatases are redox regulated and play important roles in inflammatory signaling. Protein phosphatase 2A (PP2A) activity can be modified by reactive oxygen species (ROS) produced by numerous stimuli, including cigarette smoke (CS).

Aims and objectives

We examined whether the alteration of an anti-oxidant, glutathione peroxidase-1 (GPx-1), in mice could affect phosphatase response against CS and impact on CS-induced emphysema.

Methods

Wild-type, GPx-1 overexpressing and knockout mice were exposed to short and long term cigarette smoke. Inflammatory responses and phosphatase activities were determined from lung tissue.

Results

Over-expression of GPx-1 protected CS-induced inflammation and airway enlargement. Knockdown of GPx-1 resulted in an exaggerated emphysema phenotype, correlating with low PP2A activity levels. Induction of PP2A activity coincided with increased protein tyrosine phosphatase 1B (PTP1B) activity and subsequent tyrosine dephosphorylation of the catalytic subunit of PP2A (Tyr307).

Conclusions

Therefore, PP2A is redox regulated by GPx-1 and contributes to the inflammatory and proteolytic responses that occur in CS driven diseases. Targeting the PP2A pathway may be effective means of treating COPD and other diseases where inflammation plays a central role.