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1.
Resuscitation ; 193: 109991, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37805062

RESUMO

INTRODUCTION: Little is known about the impact of tidal volumes delivered by emergency medical services (EMS) to adult patients with out-of-hospital cardiac arrest (OHCA). A large urban EMS system changed from standard adult ventilation bags to small adult bags. We hypothesized that the incidence of return of spontaneous circulation (ROSC) at the end of EMS care would increase after this change. METHODS: We performed a retrospective analysis evaluating adults treated with advanced airway placement for nontraumatic OHCA between January 1, 2015 and December 31, 2021. We compared rates of ROSC, ventilation rate, and mean end tidal carbon dioxide (ETCO2) by minute before and after the smaller ventilation bag implementation using linear and logistic regression. RESULTS: Of the 1,994 patients included, 1,331 (67%) were treated with a small adult bag. ROSC at the end of EMS care was lower in the small bag cohort than the large bag cohort, 33% vs 40% (p = 0.003). After adjustment, small bag use was associated with lower odds of ROSC at the end of EMS care [OR 0.74, 95% CI 0.61 - 0.91]. Ventilation rates did not differ between cohorts. ETCO2 values were lower in the large bag cohort (33.2 ± 17.2 mmHg vs. 36.9 ± 19.2 mmHg, p < 0.01). CONCLUSION: Use of a small adult bag during OHCA was associated with lower odds of ROSC at the end of EMS care. The effects on acid base status, hemodynamics, and delivered minute ventilation remain unclear and warrant additional study.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Retrospectivos , Retorno da Circulação Espontânea , Respiração Artificial
2.
Afr Health Sci ; 23(1): 592-595, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37545947

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a rare variant of thrombotic microangiopathy. We report a case of TTP in a Nigerian chronic kidney disease (CKD) patient who was previously on clopidogrel. The features of TTP resolved soon after clopidogrel was withdrawn. Clopidogrel is a cardio-protective anti-platelet drug used in CKD patients at risk of dyspepsia. However, its potential to cause TTP should be recognized and considered in acute kidney injury (AKI) patients previously on clopidogrel.


Assuntos
Púrpura Trombocitopênica Trombótica , Insuficiência Renal Crônica , Humanos , Clopidogrel/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Púrpura Trombocitopênica Trombótica/diagnóstico , Ticlopidina/efeitos adversos
3.
Biomed Res Int ; 2022: 2442338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158889

RESUMO

Background: Fetal fibronectin is a useful biomarker in the diagnosis and management of preterm labour. Objectives: To evaluate the relationship between cervical fetal fibronectin and preterm delivery and the association between cervical fetal fibronectin level and gestational age at delivery. Materials and Methods: A prospective cohort study was performed in a tertiary hospital in Nigeria, involving equal number of pregnant women with (96) and without (96) preterm labour. Fetal fibronectin assay was done using solid-phase immunogold assay. The data were analysed using IBM SPSS version 24. Descriptive and inferential statistical analyses were done. The level of significance was p-value <0.05. Results: Less than half (47.9%) of the women in the study group had preterm delivery while 13.09% of the women in the control group delivered preterm. Fetal fibronectin test had a sensitivity, specificity, positive predictive value and negative predictive value of 78%, 86.5%, 71.9%, and 89.0%, respectively, a positive likelihood ratio and negative likelihood ratio of 5.76(95% CI, 3.67 - 9.64) and 0.26(95% CI, 0.16 - 0.41), respectively. Conclusion: The findings in our study value of fetal fibronectin in predicting preterm delivery. Its use will support less intervention for patients with negative results.


Assuntos
Trabalho de Parto Prematuro , Nascimento Prematuro , Biomarcadores , Colo do Útero , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Fibronectinas , Humanos , Recém-Nascido , Nigéria , Trabalho de Parto Prematuro/diagnóstico , Valor Preditivo dos Testes , Gravidez , Nascimento Prematuro/diagnóstico , Estudos Prospectivos , Sensibilidade e Especificidade
4.
SAGE Open Med ; 10: 20503121221127160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172570

RESUMO

Objective: The aim of this study was to determine the pattern and outcomes of higher-order multiple pregnancies in a tertiary hospital in Nigeria. Methods: This is a retrospective review of all cases of higher-order multiple pregnancies that were managed between 1 January 2012 and 31 December 2016 in Alex Ekwueme Federal University Teaching Hospital Abakaliki, Nigeria. Data obtained were represented with frequency tables, percentages, bar charts, and odds ratio. Results: There were 22 higher-order multiple pregnancies over the study period and 12,002 deliveries, giving a higher-order multiple prevalence rate of 0.2%. Five of the mothers (four triplets and one quadruplet) had in vitro fertilization (0.4 per 1000 deliveries), while other mothers conceived naturally. Many of the women (12, 54.6%) were in the 30-34 years age group, and more than half (16, 72.7%) were multiparas. More than half of the neonates were delivered preterm (13, 59.1%). Being booked is associated with better neonatal outcomes although not significant (odds ratio = 3.06. 95% confidence interval: 0.55-16.83, p = 0.197). Anemia was common in the antepartum and postpartum periods. Half of the women (11, 50%) were delivered by elective cesarean section and 7 (31.8%) by emergency cesarean section (C/S), while 4 (18.2%) had a spontaneous vaginal delivery. The neonates had a mean birth weight of 2.14 ± 0.35 kg. Overall, 61 neonates (91.0%) were born alive and 6 (9.0%) suffered perinatal deaths, giving a perinatal mortality rate of 89.8 neonates per 1000 live births. Conclusion: Our study shows that higher-order multiple pregnancies are high-risk pregnancies that are associated with fetal and maternal complications. Anemia is the commonest complication seen in our study. The majority had preterm delivery. Proper antenatal care and close feto-maternal monitoring are important in reducing adverse outcomes associated with these pregnancies.

5.
Ghana Med J ; 56(2): 55-63, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37449262

RESUMO

Objective: To determine the efficacy of intravenous tranexamic acid versus rectal misoprostol in decreasing intraoperative blood loss during caesarean section (C/S). Design and Setting: Randomised controlled study involving pregnant women undergoing C/S at Alex Ekwueme Federal University Teaching Hospital, Abakaliki in Nigeria. Participants and Interventions: Five hundred and fourteen women undergoing elective C/S were assigned randomly (257 patients per group) to receive either pre-operative 1000 µg rectal misoprostol or 1000mg intravenous tranexamic acid after spinal anaesthesia. Data from 248 patients were analysed in the misoprostol group, while data from 250 patients were analysed in the tranexamic acid group. Sixteen patients were excluded from analysis; nine had incompletely filled proforma, while seven were lost to follow-up. Main outcome: Intraoperative blood loss. Results: The mean intraoperative blood loss was not significantly different between the misoprostol group and the tranexamic acid group (547 ± 183.75ml vs. 551.66 ± 21.74ml, P = 0.157). The mean difference in pack cell volume (PCV) changes was not significant between the groups (2.41±0.95% vs. 2.36±0.56%, P = 0.474). The side effects profile was similar for both groups except for shivering, which was statistically higher among the misoprostol group (RR = 0.70; 95%CI 0.40 - 0.91, P = 0.028). Conclusion: Intravenous tranexamic acid was comparable to rectal misoprostol in the reduction of blood loss during C/S. Tranexamic acid could act as a good alternative to misoprostol for prophylaxis for blood loss during elective C/S. Funding: None declared.


Assuntos
Misoprostol , Ocitócicos , Ácido Tranexâmico , Feminino , Humanos , Gravidez , Misoprostol/uso terapêutico , Ocitócicos/efeitos adversos , Cesárea/efeitos adversos , Ácido Tranexâmico/uso terapêutico , Ocitocina/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle
6.
Biomed Res Int ; 2021: 9008772, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34977248

RESUMO

BACKGROUND: In recent times, it has become a common practice to discharge a woman early after an uncomplicated caesarean section (CS), to satisfy their wishes, reduce cost, and maximize efficient use of healthcare system resources. OBJECTIVE: To conduct a comparative analysis of maternal and neonatal outcomes following day two hospital discharge versus day 5 or 7 discharge after an uncomplicated CS. MATERIALS AND METHODS: Eligible parturient (228) who met the inclusion criteria were randomized into two groups between 1st October 2018 and 30th September 2019 in two different maternity centers in Ebonyi state. The study group (114) was discharged two days after an uncomplicated CS while the control group (114) was discharged on the 5th or 7th postoperative day. Their satisfaction, cost, morbidities, and breastfeeding practices were evaluated using a pretested questionnaire. Data were analyzed using IBM SPSS version 22. RESULTS: Day 2 discharge was not associated with a higher rate of readmission as compared with day 5-7 discharge (χ 2 = 0.95, P = 0.329). There were no statistically significant differences in cost incurred by patients discharged on day 2 after uncomplicated CS compared to the control group (χ 2 = 1.65, P = 0.649). Maternal satisfaction was high following day 2 discharge compared with day 5-7 discharge (χ 2 = 16.64, P = 0.0001, OR = 0.857, 95%CI = 0.59-1.25). The majority of mothers (79.6%) discharged on day 2 were able to initiate and sustain breastfeeding with no statistically significant difference in the initiation and sustenance of breastfeeding with those discharged on days 5-7 (χ 2 = 4.45, P = 0.108). Early hospital discharge did not have any significant negative impact on neonatal health (χ 2 = 1.063, P = 0.303). CONCLUSION: Early discharge of patients after an uncomplicated CS is not associated with increased rate of readmission. It is associated with good maternal satisfaction, adequate initiation and sustenance of breastfeeding, and good neonatal wellbeing. We advocate early discharge of women following uncomplicated CS.


Assuntos
Cesárea/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Mães/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Adulto , Feminino , Humanos , Recém-Nascido , Readmissão do Paciente/estatística & dados numéricos , Gravidez , Fatores de Tempo , Adulto Jovem
7.
Acta Obstet Gynecol Scand ; 100(4): 694-703, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33351989

RESUMO

INTRODUCTION: Infection is one of the most common causes of maternal morbidities and mortality and has been reported to be responsible for about 15% of maternal deaths. Any woman is at risk of infection during childbirth, but women undergoing cesarean section are at higher risk. Improvement in surgical procedures with asepsis and the use of antibiotics have helped reduce postoperative infectious morbidities. However, ascending infection from the lower to the upper genital tract is a common but often neglected source of infection. Cleaning the vagina with chlorhexidine antiseptic solution before cesarean section can be a cheap and affordable source of infection control. This study is aimed at evaluating the efficacy of preoperative vaginal cleansing using 1.0% chlorhexidine in the reduction of post-cesarean section infectious morbidities. MATERIAL AND METHODS: This prospective randomized control trial was conducted among 322 pregnant women who underwent an emergency cesarean section at Alex Ekwueme Federal University Teaching Hospital, Abakaliki (AE-FUTHA). The women were randomized into two groups. The interventional group received vaginal cleansing with three standard gauzes soaked in 30 mL 1.0% chlorhexidine gluconate solution preoperatively in addition to surgical skin cleaning with chlorhexidine-alcohol. The women in the control group only had surgical skin cleaning with chlorhexidine-alcohol. All the women received pre- and postoperative antibiotics. The primary outcomes were endometritis and wound infections. RESULTS: Infectious morbidity was significantly reduced from 36.8% in the control group to 12.0% in the intervention group (P = .001). Endometritis occurred significantly less frequently in the intervention group than the control group (respectively 6.6% compared with 27.6%: relative risk [RR] 0.29, 95% confidence interval [CI] 0.16-0.53; P < .05). Foul-smelling vaginal discharge was significantly more common in the control group than in the intervention group (11.8% vs 1.3%, respectively) but the CI was wide (RR 8.5, 95% CI 1.30-64.55; P < .001). Fever and wound infection were more common in the control group (5.9% vs 3.3% and 9.2% vs 5.3%) but the difference was not significant. The hospital stay was significantly shorter among the intervention group (5.54 ± 1.04 days compared with 6.01 ± 1.55 days, P < 0.05). The most common microbial isolate implicated in endocervical colonization was Staphylococcus aureus followed by Klebsiella species. CONCLUSIONS: Vaginal cleansing with 1.0% chlorhexidine gluconate solution before emergency cesarean section appears to be effective in reducing rates of post-cesarean section infectious morbidity in the study area. We recommend its use among women undergoing cesarean section to help reduce the contribution of infections to a poor obstetrics outcome.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Cesárea , Clorexidina/administração & dosagem , Infecção da Ferida Cirúrgica/prevenção & controle , Administração Intravaginal , Feminino , Humanos , Nigéria , Gravidez , Cuidados Pré-Operatórios , Estudos Prospectivos
8.
Int J Gynaecol Obstet ; 151(2): 197-202, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32608513

RESUMO

OBJECTIVE: To determine the knowledge, attitude, and practice of antenatal attendees towards COVID-19 in Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Nigeria. METHODS: A cross-sectional survey was carried out among 430 consenting pregnant women attending antenatal clinics between March 1 and May 30, 2020, using pretested questionnaires. RESULTS: The mean age and mean gestational age of the respondents were 30.04 years (95% confidence interval [CI] 28.9-31.1) and 26.3 weeks (95% CI 23.3-29.3), respectively. More than four-fifths (82%) of the women believed that COVID-19 is real and their main source of information was mass media. The majority had adequate knowledge of COVID-19. More than half of the respondents said COVID-19 is a curable disease and that chloroquine can be used. The majority showed a good attitude and preventive practice of COVID-19 disease; however, one-fourth (24%) thought that infected individuals should be killed to prevent the spread of the virus. CONCLUSION: The study population has good knowledge, attitude, and practice of COVID-19 disease. However, it is worrisome that some respondents thought that infected individuals should be killed. Proper education must be given to the populace to avert these negative attitudes while promoting a positive preventive attitude. The study population has adequate knowledge, good attitude, and preventive practice of COVID-19; however, community education is needed to reduce anxiety among the populace.


Assuntos
Atitude Frente a Saúde , Infecções por Coronavirus , Conhecimentos, Atitudes e Prática em Saúde , Controle de Infecções , Pandemias , Pneumonia Viral , Complicações Infecciosas na Gravidez , Adulto , Betacoronavirus , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/psicologia , Estudos Transversais , Feminino , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Determinação de Necessidades de Cuidados de Saúde , Nigéria/epidemiologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/psicologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , SARS-CoV-2 , Percepção Social , Centros de Atenção Terciária
9.
Heliyon ; 6(5): e04018, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32518847

RESUMO

BACKGROUND: Menstruation has a variable pattern. Knowledge of age at menarche and providing accurate information to adolescent girls is necessary to allay anxiety, treat menstrual morbidities, and improve their quality of life. OBJECTIVE: To determine the age at menarche and menstrual characteristics of adolescent secondary school girls in Abakaliki. MATERIALS AND METHODS: A cross-sectional descriptive study was conducted in seven secondary schools in Abakaliki among 960 female students. A total of 450 girls were randomly selected for the study. A pretested self-administered questionnaire was used in data collection. Four hundred questionnaires were properly filled and used for the final analysis. RESULTS: The age range of the students was between 10 - 21years. The mean age of the respondents was 16.2 ± 1.7years. The average age at menarche was 13 ± 1.0 years. Urban dwellers had menarche 0.2years earlier than rural dwellers. There is an association between menarche and social class (X [2] 372.9 (2), p = 0.001). About 87.75% of the respondents had an average cycle length. Most (88.3%) of the respondents had a menstrual flow duration of 3-5 days. Dysmenorrhoea was present in 82% of respondents and was severe enough to cause absence from school in 56.5% of students. Oligomenorrhea and menorrhagia occurred in 8.5 % and 6.25 % of the student studied. Mothers (80.0%), friends (75.0%) and teachers (74.5%) accounted for the bulk of the information on menstrual health. CONCLUSION: The average age at menarche was 13 ± 1.0 years. Dysmenorrhea is a major cause of morbidity amongst this age group and should be empathically addressed. It is therefore important that the students, their parents, and school managers in the study area be educated on the issues of menstrual problems that can occur in an adolescent.

10.
ScientificWorldJournal ; 2020: 8273154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410909

RESUMO

BACKGROUND: Induction of labour is not without risk, and it calls for a method that will be sensitive enough to predict successful labour induction. AIM: This study aims to evaluate the role of transvaginal ultrasonographic cervical length measurement at term in the prediction of successful induction of labour (IOL). MATERIALS AND METHODS: This prospective study was carried out in the Department of Obstetrics and Gynaecology of Federal Teaching Hospital Abakaliki between 1st of July and 30th of November 2015. Preinduction Bishop score and cervical length were assessed before induction of labour. Intracervical, cervical, extraamniotic Foley catheter was used to improve the Bishop score. The data were analyzed using the IBM SPSS Statistics 20. RESULTS: The mean maternal age of the study group was 30.68 ± 6.38 years with a range of 19-43 years. The mean gestational age and parity were 39.57 ± 1.49 and 1.85 ± 0.63, respectively. All the women studied had successful induction of labour with mean induction delivery time of 8.1 ± 3.0 hours and mean duration of labour of 7.4 ± 2.9 hours. Preinduction cervical length is a good predictor of a short duration of labour (P = 0.001). Parturient with a preinduction cervical length of less than 3 cm was likely to have labour lasting less than 6 hours (RR = 4.20 (95% CI 1.85-9.529). CONCLUSION: Transvaginal sonographic measurement of cervical length provides a useful prediction of the likelihood of duration of labour following the induction of labour. It is recommended that IOL should be considered and success anticipated in a parturient with a cervical length less than 3 cm.


Assuntos
Medida do Comprimento Cervical , Colo do Útero/anatomia & histologia , Colo do Útero/diagnóstico por imagem , Resultado da Gravidez/epidemiologia , Ultrassonografia , Adulto , Medida do Comprimento Cervical/métodos , Feminino , Humanos , Trabalho de Parto Induzido , Nigéria/epidemiologia , Paridade , Gravidez , Fatores de Risco , Fatores de Tempo , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-31396592

RESUMO

BACKGROUND: Female genital mutilation (FGM) is an assault on womanhood. OBJECTIVE: To compare the obstetric outcome between parturient with genital mutilation with a cohort that has no genital mutilation. MATERIALS AND METHODS: This cross-sectional prospective study was done in the labour ward of Federal Teaching Hospital Abakaliki between 1st January 2013 and 31st December 2013. The obstetrics outcome of 260 consenting healthy parturients with FGM in the 1st stage of labour was compared with 260 cohorts with no FGM and also in labour. Data were obtained with a structured questionnaire and analysed using IBM SPSS Statistic version 20. Simple percentage odd ratio and Chi-square were used for data analysis at a p-value of < 0.05. RESULTS: The mean age and gestational age of the women were 27.9 ± 4.8 years and 38.9 ± 1.5 weeks respectively. Majority of the women, 308 or 77.0%, belonged to social class 4 and 82.0% had Type 2 FGM. More than 90.0% of the women had a vaginal delivery and the 2nd stage of labour lasted more than 2 h in 13.4% of the women (OR = 0.78 95% CI 0.64-0.97). Parturient with FGM had increased odd of perineal tear (OR = 0.76 95% CI 0.63 - 0.91) and episiotomy (OR = 1.69 95% CI 1.17-2.45). The mode of delivery and neonatal Apgar scores were not significantly influenced by the presence of FGM (P > 0.05). CONCLUSION: The study has shown that FGM in labour increases the odds of developing perineal trauma which may be associated with a host of short- and long-term complications. We recommend continued awareness creation to stop FGM.

12.
Respir Med Case Rep ; 20: 137-140, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28217439

RESUMO

Specific oncogenes with driver mutations, such as the Epidermal Growth Factor Receptor (EGFR 1) gene can lead to non-small-cell lung cancer formation. Identification of these oncogenes, their driver mutations and downstream effects allow the targeting of these pathways by drugs. Such personalised therapy has become an important strategy in combating lung cancer and highlights the need to test for these mutations. Tyrosine Kinase Inhibitors (TKIs) against EGFR, such as Erlotinib, are able to halt these tumour promoting properties in non-small-cell lung cancers. Third generation EGFR TKIs, such as Osimertinib, are focussing on resulting acquired TKI resistance. Here we report the clinical course of a patient with metastatic non-small-cell lung cancer who has undergone EGFR targeted therapy and been further challenged by TKI acquired resistance. Her extended survival and maintained quality of life are a consequence of these modern, genotype-targeted, personalised metastatic non-small-cell lung cancer therapies.

14.
Haemophilia ; 20(1): e1-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24118548

RESUMO

An increasing number of individuals with haemophilia and other severe bleeding disorders who are ≥40 years of age are entering uncharted territory with respect to the identification and management of medical, physical and social issues relevant to ageing with a bleeding disorder. This is because the population experienced considerable mortality during the HIV/AIDs and hepatitis C epidemic due to exposure to tainted blood products for treatment of bleeding. As a result, few older individuals with this disorder survive today. To provide insight for how the comprehensive care team can adapt to the changing needs of the adult haemophiliac we evaluated the patient perspective. The objective of this study was to identify key themes of importance in the ageing population with haemophilia and other inherited bleeding disorders. For this study all subjects with a diagnosis of haemophilia A or B, von Willebrand disease or rare bleeding disorders 40 years or older from a single clinic were invited to participate. Audio-recordings of groups of six to eight participants were conducted by an independent investigator without content expertise. Transcripts were analysed using N*vivo (v. 8) software using thematic content analysis. Overall, 32 subjects, 18 men/14 women, with a mean age of 57.5 years (median 56.0 years) and range of 40-77 years, participated. Three major themes emerged: (i) reflection on living an active life, (ii) 'normal' ageing vs. disease-specific impacts and (iii) the health system, and its ability to respond to their needs as ageing individuals with bleeding disorders. We found some anticipated themes and some unexpected ones, confirming that true perspective can only be provided by the patients themselves. Knowledge of these important themes has informed the development of new programmes aimed at this growing segment of the patient population.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/epidemiologia , Adulto , Fatores Etários , Idoso , Feminino , Grupos Focais , Hemofilia A/epidemiologia , Hemofilia B/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Qualidade de Vida , Fatores Sexuais , Inquéritos e Questionários , Doenças de von Willebrand/epidemiologia
15.
FEBS J ; 277(2): 441-52, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20015077

RESUMO

EVI1 is a nuclear zinc finger protein essential to normal development, which participates in acute myeloid leukaemia progression and transforms Rat1 fibroblasts. In this study we show that enforced expression of Evi1 in Rat1 fibroblasts protects from paclitaxel-induced apoptosis, consistent with previously published studies. Surprisingly, however, these cells show increased sensitivity to hydrogen peroxide (H(2)O(2))-induced apoptosis, demonstrated by elevated caspase 3 catalytic activity. This effect is caused by a reduction in carbonic anhydrase III (caIII) production. caIII transcripts are repressed by 92-97% by Evi1 expression, accompanied by a similar reduction in caIII protein. Reporter assays with the rat caIII gene promoter show repressed activity, demonstrating that Evi1 either directly or indirectly modulates transcription of this gene in Rat1 cells. Targeted knockdown of caIII alone, with Dicer-substrate short inhibitory RNAs, also increases the sensitivity of Rat1 fibroblasts to H(2)O(2), which occurs in the absence of any other changes mediated by Evi1 expression. Enforced expression of caIII in Evi1-expressing Rat1 cells reverts the phenotype, restoring H(2)O(2) resistance. Together these data show that Evi1 represses transcription of caIII gene expression, leading to increased sensitivity to H(2)O(2)-induced apoptosis in Rat1 cells and might suggest the basis for the development of a novel therapeutic strategy for the treatment of leukaemias and solid tumours where EVI1 is overexpressed.


Assuntos
Apoptose/efeitos dos fármacos , Anidrase Carbônica III/genética , Proteínas de Ligação a DNA/fisiologia , Peróxido de Hidrogênio/farmacologia , Proto-Oncogenes/fisiologia , Fatores de Transcrição/fisiologia , Animais , Apoptose/genética , Apoptose/fisiologia , Sequência de Bases , Anidrase Carbônica III/antagonistas & inibidores , Caspase 3/metabolismo , Linhagem Celular , Primers do DNA/genética , Proteínas de Ligação a DNA/genética , Regulação para Baixo/efeitos dos fármacos , Proteína do Locus do Complexo MDS1 e EVI1 , Camundongos , Paclitaxel/farmacologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Proto-Oncogenes/genética , RNA Interferente Pequeno/genética , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fatores de Transcrição/genética , Transfecção
19.
AIDS Res Hum Retroviruses ; 17(14): 1333-44, 2001 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-11602044

RESUMO

The immunologic and virologic factors that impact on the rate of disease progression after acute infection with human immunodeficiency virus (HIV) type 1 are poorly understood. A patient with an extraordinarily rapid disease course leading to AIDS-associated death within 6 months of infection was studied intensively for the presence of anti-HIV immune reactivities as well as changes in the genetic and biologic properties of virus isolates. Although altered humoral responses were evident, the most distinctive immunologic feature was a nearly complete absence of detectable HIV-specific CTL responses. In addition to a rapid decline in CD3+CD4+ cells, elevated percentages of CD8+CD45RA+ and CD8+CD57+ cells and diminished CD8+CD45R0+ and CD8+CD28+ cells were evident. Primary viral isolates recovered throughout the course of infection exhibited limited sequence diversity. Cloned viral envelopes were found to have unusually broad patterns of coreceptor usage for cell-cell fusion, although infectivity studies yielded no evidence of infection via these alternative receptors. The infectivity studies demonstrated that these isolates and their envelopes maintained an R5 phenotype throughout the course of disease. The absence of demonstrable anti-HIV CTL reactivities, coupled with a protracted course of seroconversion, highlights the importance of robust HIV-specific immune responses in the control of disease progression.


Assuntos
Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/fisiopatologia , HIV-1/fisiologia , Doença Aguda , Adulto , Sequência de Aminoácidos , Biomarcadores , Linfócitos T CD4-Positivos/imunologia , Citotoxicidade Imunológica , Progressão da Doença , Suscetibilidade a Doenças , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Soropositividade para HIV/sangue , HIV-1/imunologia , HIV-1/isolamento & purificação , Humanos , Subpopulações de Linfócitos/imunologia , Masculino , Dados de Sequência Molecular , RNA Viral/sangue , Receptores de HIV/metabolismo , Linfócitos T Citotóxicos/imunologia , Carga Viral , Replicação Viral
20.
Mol Cell Biol ; 21(15): 4949-59, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11438652

RESUMO

Development of a multicellular organism requires that mitosis and morphogenesis be coordinated. These processes must also be synchronized during the growth of unicellular organisms. In the yeast Saccharomyces cerevisiae, mitosis is dependent on the prior growth of a daughter cell in the form of a bud. Overexpression of wild-type Polo-like kinase Cdc5 or a catalytically inactive form resulted in the formation of multinucleate cells in budding yeast. Immunofluorescence analysis of these multinulceate cells showed that mitosis and bud formation were no longer linked. Others have shown that Swe1 is required for coupling mitosis to bud formation during a perturbed cell cycle. When the normal pathway of bud formation is perturbed, Swe1 functions to delay mitosis through negative regulation of Clb/Cdk. In cells lacking Swe1, multinucleate cells are formed in response to delays in bud formation. Affinity purification, two-hybrid analysis, and mutant characterization results suggested that Cdc5 and Swe1 interact. From these results, we conclude that multinucleate formation in response to Cdc5 overexpression is linked to titration of Swe1 function. These results also suggest that Cdc5 may be a negative regulator of Swe1.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Drosophila , Proteínas Nucleares , Proteínas Tirosina Quinases/metabolismo , Saccharomycetales/metabolismo , Núcleo Celular/metabolismo , Separação Celular , Citometria de Fluxo , Galactose/metabolismo , Genótipo , Glutationa Transferase/metabolismo , Microscopia de Fluorescência , Mitose , Fenótipo , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ligação a RNA , Proteínas Recombinantes de Fusão/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomycetales/enzimologia , Proteínas de Schizosaccharomyces pombe , Temperatura , Fatores de Tempo , Técnicas do Sistema de Duplo-Híbrido
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