Objawowe leczenie duszności silnymi opioidami i wpływ tej terapii na wentylację u chorych leczonych paliatywnie

W badaniu oceniano wpływ terapii opioidami na wentylację u chorych odczuwających duszność, objętych opieką paliatywną, których leczono objawowo za pomocą silnych opioidów. Dokonano pomiarów zmian wysycenia tlenem obwodowej krwi tętniczej (SaO2), przezskórnego ciśnienia dwutlenku węgla we krwi tętniczej (tcPCO2), częstości oddechów (f) i częstości akcji serca (PR) podczas fazy miareczkowania morfiny lub hydromorfonu. Celem pracy było zweryfikowanie skuteczności opioidów w opanowywaniu duszności, a także ocena ich wpływu na wentylację oraz wykazanie, czy donosowe podawanie tlenu przed zastosowaniem opioidu prowadzi do zmniejszenia nasilenia duszności. Do tego prospektywnego badania bez randomizacji włączono 11 chorych, których przyjęto na oddział opieki paliatywnej, w którym pracują autorzy niniejszej pracy. Przy przyjęciu u wszystkich chorych występowała duszność. Parametry takie jak tcPCO2, SaO2 i PR mierzono przezskórnie za pomocą SenTec Digital Monitor (SenTec AG, Szwajcaria). Podczas stosowania O2 natężenie duszności nie zmieniało się, natomiast opioidy powodowały znaczne zmniejszenie nasilenia duszności (p = 0,003). Średnia f obniżała się już po 30 minutach od pierwszego podania opioidów - z 41,8 ± 4,7 (35,0-50,0) do 35,5 ± 4,2 (30,0-40,0), a po upływie 90 minut do 25,7 ± 4,5 (20,0-32,0) oddechów/min. Natomiast inne monitorowane parametry oddechowe nie wykazywały istotnych zmian. Nie zaobserwowano depresji oddechowej spowodowanej opioidami

A MIF haplotype is associated with the outcome of patients with severe sepsis: a case control study

<p>Abstract</p> <p>Background</p> <p>Macrophage migration inhibitory factor (MIF) plays an important regulatory role in sepsis. In the promoter region a C/G single nucleotide polymorphism (SNP) at position -173 (rs755622) and a CATT_5-8microsatellite at position -794 are related to modified promoter activity. The purpose of the study was to analyze their association with the incidence and outcome of severe sepsis.</p> <p>Methods</p> <p>Genotype distributions and allele frequencies in 169 patients with severe sepsis, 94 healthy blood donors and 183 postoperative patients without signs of infection or inflammation were analyzed by real time PCR and Sequence analysis. All included individuals were Caucasians.</p> <p>Results</p> <p>Genotype distribution and allele frequencies of severe sepsis patients were comparable to both control groups. However, the genotype and allele frequencies of both polymorphisms were associated significantly with the outcome of severe sepsis. The highest risk of dying from severe sepsis was detectable in patients carrying a haplotype with the alleles -173 C and CATT₇(p = 0.0005, fisher exact test, RR = 1,806, CI: 1.337 to 2.439).</p> <p>Conclusion</p> <p>The haplotype with the combination of the -173 C allele and the -794 CATT₇allele may not serve as a marker for susceptibility to sepsis, but may help identify septic patients at risk of dying.</p

Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis

ABSTRACT: INTRODUCTION: In transgenic animal models of sepsis, members of the Bcl-2-family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro- and anti-apoptotic members of the Bcl-2-family of proteins in patients with early stage severe sepsis. METHODS: In this prospective case-control study patients were recruited from three intensive care units in a university hospital. Sixteen patients were enrolled as soon as they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and eleven healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine (PS) externalization in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed by flow cytometry. Specific mRNA's of Bcl-2 family members were quantified from whole blood by real-time polymerase chain reaction. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc testing was performed. RESULTS: In all lymphocyte populations caspase-3 (p<0.05) was activated, which was reflected in an increased PS externalization (p<0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p<005) and in B-cells (p<0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared to critically ill patients (p<0.001) and 51.6 fold as compared to healthy controls (p<0.05). Bid was increased 12.9 fold compared to critically ill (p<0.001). In the group of the mitochondrial apoptosis-inducers, Bak was upregulated 5.6 fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p<0.001, p<0.05). CONCLUSIONS: In early severe sepsis a gene expression pattern with induction of the pro-apoptotic Bcl-2 family members Bim, Bid and Bak and a downregulation of the anti-apoptotic Bcl-2 and Bcl-xl was observed in peripheral blood. This constellation may affect cellular susceptibility to apoptosis and complex immune dysfunction in sepsis

Incidence and predictors of new-onset constipation during acute hospitalisation after stroke

Objectives: We investigated new-onset constipation in patients with stroke compared with orthopaedic conditions and explored the predictors associated with constipation during acute hospitalisation. Methods: This was a prospective matched cohort study of 110 patients comparing stroke patients (n = 55) with orthopaedic patients (n = 55) admitted to a large tertiary acute hospital. Both cohorts were matched by age and sex. The incidence of new-onset constipation which occurred during a patient's acute hospitalisation was determined. Demographics, comorbidity, clinical factors, laboratory parameters and medications were evaluated as possible predictors of constipation. Results: The incidence of new-onset constipation was high for both stroke (33%) and orthopaedic patients (27%; p = 0.66). Seven stroke patients (39%) and four orthopaedic patients (27%) developed their first onset of constipation on day 2 of admission. Mobility gains (RR 0.741, p < 0.001) and the use of prophylactic laxatives (RR 0.331, p < 0.01) had a protective effect against constipation. Bedpan use (RR 2.058, p < 0.05) and longer length of stay (RR 1.032, p < 0.05) increased the risk of developing new-onset constipation. Conclusions: New-onset constipation is common among patients admitted for stroke and orthopaedic conditions during acute hospitalisation. The early occurrence, on day 2 of admission, calls for prompt preventive intervention for constipation

Оценка воздействия на атмосферный воздух деятельности компрессорной станции

Объектом исследования является поступление в атмосферный воздух выбросов от источников компрессорной станции "Вертикос", расположенной в Каргасокском районе Томской области. Цель работы – оценить загрязнение атмосферы выбросами компрессорной станции. В процессе исследования изучены стандарты Газпрома, методики расчетов выбросов загрязняющих веществ при эксплуатации компрессорной станции. В результате исследования получены значения массовых выбросов загрязняющих веществ, которые можно использовать при разработке нормативов выбросов из источников станции.The object of the research is the release of atmospheric emissions from sources of the “Verticos” compressor station located in the Kargasoksky district of the Tomsk region. The purpose of the work is to estimate the pollution of the atmosphere by the emissions from the compressor station. In the process of the research, Gazprom standards, methods for calculating pollutant emissions during the operation of the compressor station were studied. As a result of the research, the values of mass emissions of pollutants that can be used for the development of emission standards from station sources have been obtained

Unraveling Molecular Signatures of Immunostimulatory Adjuvants in the Female Genital Tract through Systems Biology

Sexually transmitted infections (STIs) unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs