Evaluation of blood reservation and use for caesarean sections in a tertiary maternity unit in south western Nigeria

<p>Abstract</p> <p>Background</p> <p>Haemorrhage from obstetric causes is the most common cause of maternal mortality in the developing world. Prevention of mortality from haemorrhage will necessarily involve prompt blood transfusions among other life saving measures. There are however limited stocks of fresh or stored blood in many health care facilities in Sub Saharan Africa. Caesarean section has been identified as a common indication for blood transfusion in obstetrics practice and its performance is often delayed by non availability of blood in our centre. An evaluation of blood reservation and use at caesarean sections in a tertiary maternity unit in Lagos, south western Nigeria should therefore assist in formulating the most rational blood transfusion policies.</p> <p>Methods</p> <p>Case records of 327 patients who had elective and emergency caesarian sections at the Lagos State University Teaching Hospital between 1^stOctober and 31^stDecember 2007 were reviewed. Data pertaining to age, parity, booking status, type and indication for Caesarean section, pre- and post-operative packed cell volume, blood loss at surgery, units of blood reserved in the blood bank, unit(s) of blood transfused and duration of hospital stay was extracted and the data analysed.</p> <p>Results</p> <p>There were 1056 deliveries out of which 327 (31%) were by Caesarean section. During the study period, a total of 654 units of blood were reserved in the blood bank and subsequently made available in theatre. Out of this number, only 89 (13.6%) were transfused to 41 patients. Amongst those transfused, twenty-six (54%) were booked and 31 (75.6%) had primary caesarian section. About 81% of those transfused had emergency caesarean section. The most common indication for surgery among those transfused were placenta praevia (9 patients with 21 units of blood) and cephalo-pelvic disproportion (8 patients with 13 units).</p> <p>Conclusion</p> <p>Even though a large number of units of blood was reserved and made available in the theatre at the time of operation, majority of the patients operated did not need blood transfusion. Provision of a mini- blood bank within the obstetric unit and careful patient categorization will ensure timely availability of blood for surgery without necessarily tying down stock in the central blood bank.</p

A new automated method for the determination of the Total Antioxidant Capacity (TAC) of human plasma, based on the crocin bleaching assay

BACKGROUND: Antioxidant molecules, which scavenge free radical species to prevent or delay oxidative damage of important macromolecules, membrane lipids and lipoproteins, are prevalent in plasma and other biological fluids. Among them, bilirubin, uric acid and protein thiols are the major endogenous antioxidants, while vitamins C and E, as well as a number of food-derived (poly)aromatic substances, belonging to stilbens, flavonoids and phenolic acids, are the main classes of nutritional antioxidants. Assays for total antioxidant capacity in plasma differ in their type of oxidation source, target and measurement used to detect the oxidized product. METHODS: In the present work we present an automated assay for the estimation of blood total antioxidant capacity (TAC assay), based on the crocin bleaching (oxidation) method. This method was adapted on a modern autoanalyzer, was linear over a wide range of values (0–3 mmol/L), and performed using an end point measurement. RESULTS: The TAC method presented a linear correlation with another automated commercial Total Antioxidant Status (TAS) test. Detection of the interference of different metabolites revealed a significant participation of TAC from uric acid, bilirubin, albumin, a minor interference from ascorbic acid, and no interference from hemoglobin. TAC was not modified by two freeze/thawing cycles, and was stable in samples stored at room temperature for 4 hours. K-EDTA and heparin were the best anticoagulants, while citrate decreased TAC by 20%. Reference values derived from samples of normal blood donors was 1.175 ± 0.007 mmol/L (mean ± SEM), while a diet rich in antioxidants more than doubled this value. CONCLUSIONS: The proposed TAC assay, is fully automated, stable and reliable, and could be of value in the estimation of the AC of plasma. It is further proposed to calculate the antioxidant capacity of plasma after a subtraction of all interference deriving from endogenous and/or exogenous metabolites. The antioxidant capacity of plasma thus calculated can be used as a useful indicator of the antioxidant value of foods and beverages in the daily diet

Specific Humoral Immunity versus Polyclonal B Cell Activation in Trypanosoma cruzi Infection of Susceptible and Resistant Mice

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 10–12 million people in Latin America. Patent parasitemia develops during acute disease. During this phase, polyclonal B cell activation has been reported to generate high levels of serum antibody with low parasite specificity, and delayed protective humoral immunity, which is necessary to prevent the host from succumbing to infection. In this manuscript, data show that relatively resistant mice have improved parasite-specific humoral immunity and decreased polyclonal B cell activation compared to susceptible mice. Parasite-specific humoral immunity was associated with differential expansion of B cell subsets and T cells in the spleen, as well as with increased Th1 and decreased Th2 cytokine production. These data suggest that host susceptibility/genetic biases impact the development of humoral responses to infection. Th2 cytokines are generally associated with improved antibody responses. In the context of T. cruzi infection of susceptible mice, Th2 cytokines were associated with increased total antibody production concomitant with delayed pathogen-specific humoral immunity. This study highlights the need to consider the effect of host biases when investigating humoral immunity to any pathogen that has reported polyclonal B cell activation during infection

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis : First-in-human trial of ChAd63-KH

BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359)

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Gamma-irradiated pollen induces the formation of 2n endosperm and abnormal embryo development in European plum (Prunus domestica L., cv. ``Rainha Cláudia Verde'')

The effect of gamma radiation on pollen germination capacity and pollen tube growth was evaluated in vitro and in situ conditions. In vitro experiments, revealed that irradiation significantly affects pollen viability, mainly for levels higher than 200 Grays (Gy). Also, for levels higher than 200 Gy, in situ observations showed that no pollen tube reached the ovule. Fruit set results confirmed that for irradiation levels higher than 200 Gy, all fruits dropped before 90 days after pollination (DAP).Most of the seeds obtained from 200 Gy pollination treatments were empty. Other seeds contained only endosperm or endosperm and embryos with abnormal development. For those seeds, flow cytometry analysis revealed sometimes the presence of a 2n endosperm, indicating that double fertilization did not occur and leading to the possibility of haploid embryo formation