A phase II irinotecan–cisplatin combination in advanced pancreatic cancer

We report a cisplatin and irinotecan combination in patients with biopsy-proven advanced pancreatic adenocarcinoma. Patients were selected from a specialist centre and required good performance status (KPS>70%), measurable disease on CT scan, and biochemical and haematological parameters within normal limits. Based on a two-stage phase II design, we aimed to treat 22 patients initially. The study was stopped because of the death of the 19th patient during the first treatment cycle, with neutropenic sepsis and multiorgan failure. A total of 89 treatments were administered to 17 patients. Serious grade 3/4 toxicities were haematological (neutropenia) 6%, diarrhoea 6%, nausea 7% and vomiting 6%. Using the clinical benefit response (CBR) criteria, no patients had an overall CBR. For responses confirmed by CT examination, there was one partial response (5%), three stable diseases lasting greater than 6 weeks (16%), with an overall 22% with disease control (PR+SD). The median progression-free and overall survival was 3.1 months (95% CI: 1.3-3.7) and 5.0 (95% CI: 3.9-10.1) months, respectively. Although this synergistic combination has improved the response rates and survival of other solid tumours, we recommend caution when using this combination in the palliation of advanced pancreatic cancer, because of unexpected toxicity

Nasopharyngeal isolates and their clinical impact on young children with asthma: a pilot study

Ahmed R Alsuwaidi,1 Alia M Alkalbani,2 Afaf Alblooshi,1 Junu George,1 Ghaya Albadi,1 Salwa M Kamal,3 Hassib Narchi,1 Abdul-Kader Souid1 1Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Tawam Hospital, Abu Dhabi Health Services Company (SEHA), Al Ain, United Arab Emirates; 3Ambulatory Healthcare Services, SEHA, Abu Dhabi, United Arab Emirates Introduction: Respiratory infections have significant effects on childhood asthma. Viral respiratory infections, such as rhinovirus and respiratory syncytial virus are likely to be important in the development and exacerbation of asthma. In this study, we investigated the nasopharyngeal colonization in children with asthma to determine the prevalence of pathogens and their contribution to respiratory symptoms and airway resistance during winter. Methods: From December 2016 to March 2017, 50 nasopharyngeal specimens were collected from 18 patients (age, 5.0±1.1 years) with asthma and 9 specimens from 9 control children (age, 4.9±1.0 years). Samples were tested for 19 viruses and 7 bacteria, using multiplex real-time PCR. Respiratory disease markers included the Global Asthma Network Questionnaire, the Common-Cold Questionnaire, the Global Initiative for Asthma assessment of asthma control, and the airway resistance at 5 Hz by forced-oscillation technique. Results: The most commonly isolated organisms in both groups (patients and controls) were Streptococcus pneumoniae, Haemophilus influenzae, and rhinovirus. Most patients had multiple isolates (median, 3.5; range, 1–5), which changed during the study period. Types of isolates were 4 bacteria (S. pneumoniae, H. influenzae, Bordetella pertussis, and Bordetella parapertussis) and 6 viruses (rhinovirus, enterovirus, metapneumovirus, adenovirus, coronaviruses, and parainfluenza viruses). Similar isolates, including influenza A-H3 virus and bocavirus, were detected in the controls. Of the 9 patients with “wheezing disturbing sleep ≥1 per week”, 6 had rhinovirus, 2 coronaviruses, and 1 no detectable viruses. Patients with mild common cold symptoms had significantly higher airway resistance at 5 Hz z-score (P=0.025). Conclusion: Multiple respiratory pathogens were isolated from many patients with asthma, which appeared to contribute to disease symptoms and airway resistance. Minimizing children’s exposure to respiratory pathogens might be beneficial, especially during winter. Keywords: asthma, inhaled corticosteroids, respiratory pathogens, nasopharyngeal colonization, communicable disease

Lung toxicities of core–shell nanoparticles composed of carbon, cobalt, and silica

Mohammed T Al Samri,1,* Rafael Silva,2,* Saeeda Almarzooqi,3 Alia Albawardi,3 Aws Rashad Diab Othman,1 Ruqayya SMS Al Hanjeri,1 Shaikha KM Al Dawaar,1 Saeed Tariq,4 Abdul-Kader Souid,1 Tewodros Asefa2,51Department of Pediatrics, United Arab Emirates University, Abu Dhabi, United Arab Emirates; 2Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; 3Department of Pathology, 4Department of Anatomy, United Arab Emirates University, Abu Dhabi, United Arab Emirates; 5Department of Chemical Engineering and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA*These authors contributed equally to this workAbstract: We present here comparative assessments of murine lung toxicity (biocompatibility) after in vitro and in vivo exposures to carbon (C–SiO2-etched), carbon–silica (C–SiO2), carbon–cobalt–silica (C–Co–SiO2), and carbon–cobalt oxide–silica (C–Co3O4–SiO2) nanoparticles. These nanoparticles have potential applications in clinical medicine and bioimaging, and thus their possible adverse events require thorough investigation. The primary aim of this work was to explore whether the nanoparticles are biocompatible with pneumatocyte bioenergetics (cellular respiration and adenosine triphosphate content). Other objectives included assessments of caspase activity, lung structure, and cellular organelles. Pneumatocyte bioenergetics of murine lung remained preserved after treatment with C–SiO2-etched or C–SiO2 nanoparticles. C–SiO2-etched nanoparticles, however, increased caspase activity and altered lung structure more than C–SiO2 did. Consistent with the known mitochondrial toxicity of cobalt, both C–Co–SiO2 and C–Co3O4–SiO2 impaired lung tissue bioenergetics. C–Co–SiO2, however, increased caspase activity and altered lung structure more than C–Co3O4–SiO2. The results indicate that silica shell is essential for biocompatibility. Furthermore, cobalt oxide is the preferred phase over the zerovalent Co(0) phase to impart biocompatibility to cobalt-based nanoparticles.Keywords: carbon nanoparticles, cobalt nanoparticles, silica nanoparticles, cobalt oxide nanoparticles, biocompatibility, nanotoxicolog

Lymphocyte respiration in children with Trisomy 21

<p>Abstract</p> <p>Background</p> <p>This study measured lymphocyte mitochondrial O₂ consumption (cellular respiration) in children with trisomy 21.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O₂] was determined as a function of time from the phosphorescence decay rates (1/τ) of Pd (II)-<it>meso</it>-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O₂] declined linearly with time, confirming the zero-order kinetics of O₂ conversion to H₂O by cytochrome oxidase. The rate of respiration (<it>k</it>, in μM O₂ min^-1), thus, was the negative of the slope of [O₂] <it>vs.</it> time. Cyanide inhibited O₂ consumption, confirming that oxidation occurred in the mitochondrial respiratory chain.</p> <p>Results</p> <p>For control children (age = 8.8 ± 5.6 years, n = 26), the mean (± SD) value of <it>k</it>_<it>c</it> (in μM O₂ per min per 10⁷ cells) was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61). For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26), the values of <it>k</it>_<it>c</it> were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80), <it>p</it><0.001. Similar results (<it>p</it><0.000) were obtained after excluding the five trisomy 21 children with elevated serum TSH (values >6.1 mU/L). Fourteen of 26 (54%) children with trisomy 21 had <it>k</it>_<it>c</it> values of 0.20 to 0.60 (i.e., <−2SD). The values of <it>k</it>_<it>c</it> positively correlated with body-mass index (BMI, <it>R</it> >0.302), serum creatinine (<it>R</it> >0.507), blood urea nitrogen (BUN, <it>R</it> >0.535) and albumin (<it>R</it> >0.446).</p> <p>Conclusions</p> <p>Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.</p