tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Effort of breathing indices in infants with acute respiratory insufficiency receiving different noninvasive respiratory supports
Authors: Stefano Luciani, Elena Caresta, Roberto Cicchetti, Rosanna Grossi, Corrado Moretti, Paola Papoff
Journal: European Respiratory Journal (2014)

BACKGROUND: High-flow nasal cannula (HFNC) has gained popularity as an alternative to noninvasive ventilation (NIV) to treat acute respiratory insufficiency (ARI) in infants and children. It is not known whether HFNC would be as effective as NIV in reducing effort of breathing (EOB) in these patients.  OBJECTIVE: To compare WOB indices between two levels of HFNC and two NIV modalities in a prospective randomized crossover study in patients ≤ 3 years of age with moderately severe ARI.  STUDY DESIGN: Respiratory inductive plethysmography and the electric activity of the diaphragm (Edi) were used to determine EOB in 8 infants (1 – 34 months) with lower respiratory tract infection during HFNC (1L/min/kg+1 or 2L/min/kg), NIV-PSV (Pressure Support Ventilation, PS 6 to 12, PEEP 5 cmH2O), NIV-NAVA (Neurally Adjusted Ventilatory Assist, NAVA level 1, PEEP 5 cmH2O), and low flow oxygen therapy (LFT) as control. Pharyngeal pressure (PP) was recorded during HFNC.  RESULTS: A statistically significant decrease in all EOB indices was observed during HFNC (2L/min/kg) and NIV as compared to LFT.  CONCLUSIONS: Both HFNC and NIV decreased EOB indices as compared with LFT, although the most significant effects were seen during NIV.
Composition Studies on Tobacco. XLI. Carcinogenesis Assay of Subtractions of the Neutral Fraction of Cigarette Smoke Condensate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Fred G. Bock, A. P. Swain, R. L. Stedman
Journal: JNCI Journal of the National Cancer Institute (1970)

Carcinogenesis assays of subfractions of the neutral fraction of cigarette smoke condensate, with mice previously treated with 7,12-dimethylbenz[a]anthracene, are reported. The most polar subfraction and the subfraction containing benzo[a]pyrene were the most active. In terms of both the relative concentration in the crude condensate and in activity per gram, the polar subfraction was as active as the benzo[a]pyrene subfraction. Two other subfractions were less active. It was not determined whether any of these fractions possesses complete carcinogenic activity or only tumor-promoting activity.
Tumorigenesis in Strain DW/J Mice and Induction by Prolactin of the Group-Specific Antigen of Endogenous C-Type RNA Tumor Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H W Chen, H Meier, H J Heiniger, R J Huebner
Journal: JNCI Journal of the National Cancer Institute (1972)

The dwarf mutation (gene symbol dw), maintained in the inbred strain DW/J, causes primary anterior pituitary endocrine defects. These defects could be remedied by prolactin, which reversed growth retardation and organ hypoplasia or atrophy, stimulated RNA and protein synthesis, and also induced the intraspecies group-specific antigen (gs-AG) of endogenous C-type RNA tumor virus. In young normal littermates, prolactin caused precocious appearance of gs-AG. Thus prolactin increased expression of genetic information, including viral gs-AG. Development of two types of tumors in a small number of DW/J heterozygotes (dw/+) and homozygous normal (+/+) mice indicated separate and possibly independent events of malignant transformation. Normal mice of either genotype had a high incidence (85%) of gs-AG expression, which increased with age. The closely associated development of reticulum cell sarcomas and gs-AG in them indicated an etiologic relationship.—J Natl Cancer Inst 49: 1145–1154, 1972.
Miltefosine as an effective choice in the treatment of post-kala-azar dermal leishmaniasis
Authors: V. Ramesh, G.K. Katara, S. Verma, P. Salotra
Journal: British Journal of Dermatology (2011)

Post-kala-azar dermal leishmaniasis (PKDL) constitutes a parasite reservoir important in the transmission of visceral leishmaniasis (VL). Unacceptable treatment regimens and increasing drug resistance blight control programmes. The success of oral miltefosine in VL prompted a clinical, histopathological and parasitological study of this drug in PKDL.To define the dose and duration of miltefosine for treatment of PKDL.Twenty-six patients confirmed by slit-skin smear, histopathology and molecular tests were enrolled in the study. They received miltefosine capsules 50 mg thrice daily after food. Treatment was for 60 days with a provision to increase by 30 days if a responder had not attained a cure. Cure was ascertained by clinical and histopathological examination, and measuring parasite burden using real-time polymerase chain reaction.Twenty-four patients with a wide range of parasite burden completed the study. Twenty-three achieved a cure giving an initial cure rate of 96% (95% confidence interval 79-99%). Sixteen patients were cured with 50 mg thrice daily, 13 in 60 days and three within 90 days. In seven cases, miltefosine had to be reduced, because of gastrointestinal intolerance, to 50 mg twice daily to a total of 180 capsules. Lesional parasites were undetectable at 1 month post-treatment. Treatment was safe with no relapses at 1-year follow-up.Oral miltefosine, 50mg thrice daily for 60 days or twice daily for 90 days, could be an effective treatment for PKDL.
Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition
Authors: Lu Gao, Elizabeth H. Rabbitt, Jennifer C. Condon, Nora E. Renthal, John M. Johnston, Matthew A. Mitsche, Pierre Chambon, Jianming Xu, Bert W. O’Malley, Carole R. Mendelson
Journal: Journal of Clinical Investigation (2015)

The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A–deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2–deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2–deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2–deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2–dependent production of SP-A and PAF is crucial for this process.
Evidence for an Inhibiting Influence of Fetal Bovine Serum on “Spontaneous” Neoplastic Transformation &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Katherine K. Sanford, Jay L. Jackson, Ram Parshad, R. Raymond Gantt
Journal: JNCI Journal of the National Cancer Institute (1972)

C3H mouse embryo cells grown in horse serum-supplemented, chemically defined medium were shown previously to undergo “spontaneous” neoplastic transformation early as compared with cells From the same cell pool grown in Fetal bovine serum supplement. These observations suggested that some component(s) of horse serum accelerates spontaneous neoplastic transformation, or that Fetal bovine serum inhibits neoplastic transformation, or that both phenomena occur. The present study supports the conclusion that fetal bovine serum does tend to inhibit spontaneous neoplastic transformation. These transformations were delayed or prevented in 4 independent sublines when Fetal bovine serum was added to a medium containing horse or calf serum in which transformations occurred early. In more limited tests with the fetuin fraction of fetal bovine serum, there appeared to be some inhibition of transformation, but the results were not conclusive.
The treatment of advanced metastatic seminoma: experience in 55 cases.
Authors: S D Fosså, L Borge, N Aass, N B Johannessen, A E Stenwig, O Kaalhus
Journal: Journal of Clinical Oncology (1987)

Thirty-six of 39 previously untreated evaluable patients with advanced metastatic seminoma (stage greater than or equal to IIb) obtained a complete response (CR) and three a partial response (PR) after cisplatin-based combination chemotherapy with or without surgery/radiotherapy (group 1). After a median observation time of 36 months, 33 patients are alive with no evidence of disease (NED). Fifteen additional patients received cisplatin-based chemotherapy due to relapsing seminoma after initial radiotherapy (group 2). Thirteen patients obtained a CR, and two a PR. Patients from group 1 lived significantly longer after the start of chemotherapy than those from group 2. The rate and severity of the treatment-related complications were comparable in both groups. The most frequent nonfatal side effects of cisplatin-based combination chemotherapy were Raynaud-like phenomena, polyneuropathy, and myelosuppression. Four patients developed fatal complications (septicemia, bone marrow aplasia). In three of 12 patients with evaluable postchemotherapy histology, vital malignant seminoma was found. Cisplatin-based combination chemotherapy in advanced seminoma patients is highly effective, but includes a significant risk of severe complications. Less toxic treatment regimens should be explored, at least for patients who have less advanced tumors (stage IIb/limited stage IIc).
Management of advanced colorectal cancer
Authors: C. Bradley, P. Selby
Journal: Annals of Oncology (1994)

In February 1989, during a holiday in Gran Canaria, a 55-year-old man was admitted as an emergency to the local hospital following several days of nausea and vomiting associated with absolute constipation. He gave a history of abdominal pain and fullness over the preceding 2 weeks, although there was no anorexia or weight loss. On examination there was generalised abdominal distension and increased bowel sounds. Plain abdominal X-ray showed dilated bowel loops and faecal loading of the ascending and transverse colon. At laparotomy, a stenosing carcinoma of colon was found at the splenic flexure. There was no evidence of disease in the liver or elsewhere in the abdomen. A left hemicolectomy and reanastomosis was performed. Histological examination of the resected specimen showed circumferential involvement with a moderately differentiated adenocarcinoma extending through the full thickness of the bowel wall into surrounding adipose tissue. One of 9 lymph nodes showed malignant infiltration.
Orthodeoxia in hypoxaemic morbid obesity reverts one year after bariatric surgery
Authors: Eva Rivas, Ebymar Arismendi, Ana Tejedor, Yolanda Torralba, Concepcion Gistau, Felip Burgos, Salvadora Delgado, Jaume Balust, Robert Rodriguez-Roisin
Journal: European Respiratory Journal (2012)

Introduction: In morbid obesity (MO), pulmonary gas exchange (GE) abnormalities are influenced by postural changes that are known to improve after bariatric surgery (BS).  Objective: To unravel the determinants of GE in MO at upright (U) and supine (S) while breathing ambient air, in random order, before and one year after BS.  Methods: 15 (14 females; 51±(SE)2 yrs; BMI, 47±2 Kg/m2) hypoxaemic -H- (PaO2, 73±5 mmHg) and 8 normoxaemic -N- (PaO2, 89±4 mmHg), matched for age, sex and BMI were studied before and after BS. GE measurements, including ventilation-perfusion (V9A /Q9) distributions were performed.  Results: Before BS, H patients at U exhibited moderate V9A /Q9 imbalance (low V9A /Q9 areas (  Conclusions: Hypoxaemic morbid obesity is associated with orthodeoxia. This novel finding may be related to a gravitational heterogeneous redistribution of pulmonary blood flow induced by systemic inflammation. Bariatric surgery reverts completely this phenomenon.  Supported by FIS (PI08031108), Esteve and CIBERES.
Germany considers legalising cannabis for medical use
Authors: Ned Stafford
Journal: BMJ (2015)

Germany’s health ministry has drafted a proposed new law that would create a government operated “cannabis agency” to oversee production of marijuana and its distribution for use in cannabis based medicines to treat pain and other ailments.

Currently cannabis can be used for medical treatment in Germany if it is prescribed by doctors, but it is generally not covered by health insurance, and the use of cannabis based medicines in Germany is negligible. Under the proposed law cannabis based medicines prescribed by doctors would …
CHOP may have been part of the beginning but certainly not the end: issues in risk-related therapy of large-cell lymphoma.
Authors: G P Canellos
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.5.1713 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9164176 CHOP may have been part of the beginning but certainly not the end: issues in risk-related therapy of large-cell lymphoma. G P CanellosxG P CanellosSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.5.1713 First Page PDF © 1997 by American Society of Clinical Oncology
Relationship Between Host Range and Isoantigenic Properties In Different Sublines of the Same Sarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Eva Klein, Erna Möller
Journal: JNCI Journal of the National Cancer Institute (1963)

Sarcoma MCAG, induced with 3-methylcholanthrene in an (A × A.CA)F1 hybrid mouse, and sublines of this sarcoma with different host range were studied with regard to H-2 isoantigens. The cells of the original F1 tumor proved asymmetric for the two parental isoantigen complexes—they appeared to contain more H-2f than H-2a. After inoculation of these cells, A.CA mice produced anti-H-2a antibodies earlier than A mice responded with anti-H-2f antibodies. The transplantation behavior of the tumor was explained on the basis of these findings. A variant subline showing strict transplantation specificity toward the parental strain A had lost the H-2 antigens derived from the A.CA parental genotype and had a considerably increased concentration of the remaining H-2a antigen complex. The loss of specificity was accompanied by decrease in the amount of the H-2 antigens on the cells.
Surrogate marker (SM) reporting in patients (pts) with advanced colorectal cancer (ACRC) of first-line clinical trials: It's time for standardized trial endpoint reporting.
Authors: H. Arkenau, T. Dobbins, I. C. Nordman, R. L. Ward
Journal: Journal of Clinical Oncology (2010)

e14010 Background: The use of SM instead of definite endpoints such as OS is an accepted method with various strategies of identification/validation being employed, i.e. meta-analytic or pts based outcome. Analysis using data from either source has advantages but the use of summary data potentially encompasses a larger number of trials and offers the opportunity for independent review. A prerequisite to using summary data from published trials is to understand the quality of the evidence base from which this data is derived. Methods: We performed a meta-analysis to assess the quality and completeness of SM reporting in pts with ACRC who underwent 1st-line treatment over a 40 yrs period. The most commonly reported trial endpoints OS, TTP, duration of response (DOR) and RR were analyzed for potential changes in time (pre-1990s, -1990s and -2000s) in a homogenous subgroup of pts who only received 5-FU based or equivalent agents (i.e., oral 5-FU, thymidylate inhibitor). Results: In total 144 ACRC RCTs including 35,853 pts were identified. The average pt taking part in these trials was male with a good PS (PS0/1), just over 60 years. 129 trials (90%) reported OS and SM were RR (90%), TTP (44%), DOR (43%) followed by PFS (22%), and to a lesser extend TTF (12%) and TTR (6%). In pts who received 5-FU based or equivalent agents (n = 28,636) at the predefined time periods the median OS increased from 9.6 months (m) (< 1990s) to 11.2 m (1990s) and finally to 13.9 m (> 2000s), p < 0.0001. The rate of SD increased from 36.2%, to 40.1% and 41.9%, p = 0.004, whereas the rates of PD decreased over the time from 42.5%, to 33.5% and 33.3%, p = 0.002. TTP (4.8 m), DOR (7.6 m) and RR (17.7%) increased from pre-1990s to the 1990s (5.8 m, 8.0 m and 22.1%) and declined marginally in the 2000s (5.3 m, 7.6 m and 18.7%, p = NS). Conclusions: We identified major deficiencies in the capture of clinical endpoints which impacted on comparing SM using a meta- analytic approach. SM varied over time in pts who received 5-FU based or equivalent agents. A standardized and clearly defined way of reporting clinical trial endpoints could greatly improve interpretation of trial results, allowing for much better comparisons between RCTs. No significant financial relationships to disclose.
Exercise-induced Bronchospasm in Children
Authors: ANNA LÚCIA B. CABRAL, GLEICE M. CONCEIÇÃO, CRÍSTÍNA H. F. FONSECA-GUEDES, MILTON A. MARTINS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The prevalence of exercise-induced bronchospasm (EIB) in asthmatic individuals has been reported to vary from 40% to 90%. There are, however, few studies addressing the effects of asthma severity on airway responsiveness to exercise. The purpose of the present study was to investigate the effects of asthma severity on EIB in children. We studied 164 children classified as having intermittent (n = 63), mild persistent (n = 30), moderate persistent (n = 40), and severe persistent asthma (n = 31) according to the Global Initiative for Asthma classification. Subjects exercised for 6 min on a cycle ergometer at 80% of their maximum heart rate, and spirometry was performed before and 5, 10, and 20 min after exercise challenge. The prevalence of EIB in children with moderate or severe persistent asthma was significantly greater than in children with intermittent asthma (p < 0.001). EIB-positive children with intermittent asthma exhibited smaller changes in FEV1 than children in the other three groups (p < 0.001). There was no significant relationship between baseline FEV1 and the decline in FEV1 after exercise. We conclude that the prevalence of EIB is greater in children with more severe asthma, and that the intensity of response to exercise is not consistently related to the clinical severity of asthma.
Indacaterol provides sustained 24 h bronchodilation on once‐daily dosing in asthma: a 7‐day dose‐ranging study
Authors: C. LaForce, M. Alexander, R. Deckelmann, L. M. Fabbri, Z. Aisanov, R. Cameron, R. Owen, M. Higgins
Journal: Allergy (2007)

Background: Indacaterol is a novel, once‐daily β 2 ‐agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation. Objective: A dose‐ranging study was undertaken to evaluate efficacy and safety of indacaterol. Methods: A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once‐daily indacaterol 50, 100, 200, or 400 μg via multi‐dose dry‐powder inhaler (MDDPI; Certihaler ™ ), indacaterol 400 μg via single‐dose dry‐powder inhaler (SDDPI), or placebo. Serial 24‐h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored. Results: All doses of indacaterol increased the mean time‐standardized area under the curve of forced expiratory volume in 1 s (FEV 1 ) from 22 to 24 h postdose ( P ≤ 0.001 vs placebo) on days 1 and 7, with clinically relevant treatment‐placebo differences of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on day 7 for indacaterol 50, 100, 200, and 400 μg via MDDPI and 400 μg via SDDPI, respectively. All doses increased mean FEV 1 ( P &lt; 0.05 vs placebo) from 5 min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse events were mild‐to‐moderate in severity: most frequently reported were respiratory, thoracic, and mediastinal disorders. Conclusion: Once‐daily dosing with indacaterol provided sustained 24‐h bronchodilation in patients with moderate‐to‐severe asthma, with a satisfactory overall safety profile. Indacaterol 200 μg appears the optimum dose, offering the best efficacy/safety balance.
LTA-T for malignant pleural effusions
Authors: J Wall
Journal: Thorax (2009)

Management of recurrent malignant pleural effusions is a common problem. At present the agent of choice is intrapleural talc, but it is not without side effects. Attention is therefore being directed toward strategies to target specific cellular mediators of the pleural inflammatory cascade. As there is fibrotic change in the pleural cavity as a result of …
A prosprective study on the safety, tolerability and efficacy of pirfinidone in the treatment of idiopathic pulmonary fibrosis and fibrotic NSIP
Authors: Ratna Balakrishnan, Sapna Madas, Bill Brasier, Sujeet Rajan
Journal: European Respiratory Journal (2012)

Prospective study conducted on 39 patients with IPF and fibrotic NSIP on patients visiting at Bombay Hospital, Mumbai. Out of 39,9 patients failed to follow up while 9 patients expired on the treatment. Drug had to be stopped in one patient due to reaction. 13% of the patients had a diagnosis proven on surgical lung biopsy. The remaining had their diagnosis confirmed on HRCT, of which 74.4% revelead honey combing and 28% revealed ground-glass opacities.

The mean FVC at baseline has been 1.78lts (57% predicted SD 19%) and 1.57(61% predicted SD 11.53) at 6 months. The mean corrected DLCO at baseline was 38.29% 39.58% at 6 months. The mean oxygen saturation at baseline 95.38% and 95.82% at 6 months. The 6 min walk test was almost the same at the end of 6 months too (329 vs 331meters). Though patients dropped to a mean saturation of 84.53% post walk at baseline, this did not significantly change 6 months either.

tThe drug has been quite well tolerated too. None of the patients have elevated liver enzymes and only one patient developed skin rash. GI discomfort and loss of appetite were other side effects that were noted. The average dose of pirfenidone taken during this period was 1082.05 mg/day and the maximum dose administered has been 1800mg/day.

Pirfinidone is the only approved drug for IPF currently available in the world. Considering its previous efficacy documented in slowing the decline in FVC, we thought it appropriate to do this observational study not just on IPF but also on fibrotic diseases to assess its tolerability over a period of time and its potential efficacy in these conditions.