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1.
Ultrasound Obstet Gynecol ; 57(1): 97-104, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32339337

RESUMO

OBJECTIVES: To compare the ability of detailed routine ultrasound examination, performed without knowledge of maternal serology and fetal status, with that of targeted prenatal imaging performed in prenatal diagnostic units in cases of known fetal infection to identify cytomegalovirus (CMV)-infected fetuses that will develop long-term sequelae. METHODS: All prenatal imaging reports were collected for 255 children with congenital CMV in a registered cohort between 2013 and 2017 (NCT01923636). All women had undergone detailed routine fetal ultrasound examination at 20-24 and 30-34 weeks as part of routine antenatal care. All cases of known fetal CMV infection had also undergone targeted prenatal ultrasound examination. Postnatal structured follow-up for up to 48 months of age involved clinical, audiological and neurological assessment, including Brunet-Lezine scoring. Long-term sequelae (> 12 months) were considered to be mild in cases with isolated unilateral hearing loss and/or vestibular disorders, and severe in cases with bilateral hearing loss and/or neurological sequelae. All imaging reports were analyzed retrospectively with the knowledge of congenital CMV infection, searching for reference to findings that were, or could have been, related to fetal infection. Findings were analyzed in relation to whether the cases were diagnosed with CMV in utero or only postnatally. RESULTS: There were 237 children with complete follow-up data (> 12 months), for a median of 24 (range, 12-48) months. Of these, 30% (71/237) were diagnosed with CMV prenatally and 70% (166/237) were diagnosed within 3 weeks after birth. 72.5% (29/40) of children with long-term sequelae, including 74% (14/19) with severe long-term sequelae, were not identified in the prenatal period. Among those diagnosed prenatally, the sensitivity of prenatal imaging for predicting long-term sequelae and severe long-term sequelae was 91% and 100%, respectively, while, in the group diagnosed only postnatally, non-specific infection-related ultrasound findings had been reported without raising suspicion in 48% of cases with long-term sequelae and 64% of those with severe long-term sequelae. CONCLUSIONS: Routine detailed ultrasound examination in pregnancy is not an appropriate screening tool for congenital CMV infection that leads to long-term sequelae, in contrast with the high performance of targeted prenatal imaging in known cases of fetal infection. The non-specific nature of ultrasound features of CMV and their evolution, and a lack of awareness of caregivers about congenital CMV, are likely explanations. Awareness of the sonologist regarding congenital CMV and knowledge of the maternal serological status in the first trimester seem key to the performance of prenatal ultrasound. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Infecções por Citomegalovirus/diagnóstico por imagem , Ultrassonografia Pré-Natal/normas , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/transmissão , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Estudos Longitudinais , Programas de Rastreamento/efeitos adversos , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez
2.
Rheumatol Int ; 37(2): 219-227, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27853860

RESUMO

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) bring relief of pain and functional disability to patients with end-stage osteoarthritis, and however, the literature on their impact on patients' level of physical activity (PA) is scarce. Cross-sectional study in patients who underwent THA/TKA surgery in the preceding 6-22 months and a random sample of persons aged >40 years from the Dutch general population, participating in a national survey. PA in minutes per week (min/week) and adherence to the Dutch recommendation for PA (NNGB yes/no) were measured by the short questionnaire to assess health-enhancing PA. Multivariable linear (total min/week) and logistic regression analyses (meeting recommendations PA), adjusting for confounders, were performed for THA and TKA separately. In total, 258 THA [62.3% female, aged 69.4 (9.1)] and 221 TKA [65.7% female, aged 69.5 (8.9)] patients and 4373 persons from the Dutch general population [51.4% female, aged 58.9 (11.6)] were included. The presence of THA was associated after adjusting for age, sex, BMI education and musculoskeletal comorbidities, with more total min/week spent on PA (THA 13.8% increase, 95% CI 1.6-27.6%), whilst both TJA groups were associated with adhering to NNGB (THA: OR 1.79, 95% CI 1.26-2.56; TKA: OR 1.73, 95% CI 1.20-2.51). As this study used questionnaires to compare the PA of THA/TKA patients to the general population, some recall and selection bias might have been induced. After surgery, overall, TJA patients are more likely to adhere NNGB than a representative sample of persons >40 years from the Dutch general population.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Exercício Físico/fisiologia , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Qualidade de Vida , Inquéritos e Questionários
3.
Rheumatol Int ; 35(7): 1233-41, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25586654

RESUMO

The aim of the study was to examine the relationship between comorbidities and pain, physical function and health-related quality of life (HRQoL) after total hip arthroplasty (THA) and total knee arthroplasty (TKA). A cross-sectional retrospective survey was conducted including 19 specific comorbidities, administered in patients who underwent THA or TKA in the previous 7-22 months in one of 4 hospitals. Outcome measures included pain, physical functioning, and HRQoL. Of the 521 patients (281 THA and 240 TKA) included, 449 (86 %) had ≥1 comorbidities. The most frequently reported comorbidities (>15 %) were severe back pain; neck/shoulder pain; elbow, wrist or hand pain; hypertension; incontinence of urine; hearing impairment; vision impairment; and cancer. Only the prevalence of cancer was significantly different between THA (n = 38; 14 %) and TKA (n = 52; 22 %) (p = 0.01). The associations between a higher number of comorbidities and worse outcomes were stronger in THA than in TKA. In multivariate analyses including all comorbidities with a prevalence of >5 %, in THA dizziness in combination with falling and severe back pain, and in TKA dizziness in combination with falling, vision impairments, and elbow, wrist or hand pain was associated with worse outcomes in most of the analyses. A broad range of specific comorbidities needs to be taken into account with the interpretation of patients' health status after THA and TKA. More research including the ascertainment of comorbidities preoperatively is needed, but it is conceivable that in particular, the presence of dizziness with falling, pain in other joints, and vision impairments should be assessed and treated in order to decrease the chance of an unfavorable outcome.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Articulação do Quadril/cirurgia , Articulação do Joelho/cirurgia , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Dor Pós-Operatória/epidemiologia , Qualidade de Vida , Idoso , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Fenômenos Biomecânicos , Distribuição de Qui-Quadrado , Comorbidade , Estudos Transversais , Feminino , Nível de Saúde , Articulação do Quadril/fisiopatologia , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos/epidemiologia , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/fisiopatologia , Prevalência , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
4.
Lymphology ; 45(4): 144-53, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23700761

RESUMO

The contribution of the lymphatic system to the absorption and systemic bioavailability of Micrurus fulvius venom after subcutaneous (SC) administration was assessed using a central lymph-cannulated sheep model. Micrurus fulvius venom was administered either by intravenous bolus (IV) or subcutaneous injection (SC) in 12 sheep with and without thoracic duct cannulation and drainage. Venom concentration in serum and lymph was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) in samples collected over a 6-hour period and in tissues harvested at the end of the experiment. Pharmacokinetic parameters were determined by a non-compartmental analysis. In the lymphatic cannulated group, over the 6 hours after the venom was administered, 69% of administered dose was accounted for in blood (45%) and lymph (25%). Negligible levels of venom were detected in organs and urine implying that the steady state observed after SC administration is maintained by a slow absorption process. Comparison of kinetics of the thoracic duct cannulated and non-cannulated groups showed that lymphatic absorption contributed in an important way to maintenance of this steady state. These results show that the limiting process in the pharmacokinetics of Micrurus fulvius venom following SC administration is absorption, and that the lymphatic system plays a key role in this process.


Assuntos
Venenos Elapídicos/farmacocinética , Elapidae , Sistema Linfático/metabolismo , Carneiro Doméstico/metabolismo , Animais , Área Sob a Curva , Disponibilidade Biológica , Transporte Biológico , Venenos Elapídicos/administração & dosagem , Feminino , Meia-Vida , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Ovinos , Distribuição Tecidual
5.
Afr J Lab Med ; 11(1): 1644, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547332

RESUMO

Background: Haemoglobinopathies are inherited haemoglobin disorders that result in anaemia characterised by erythrocyte anisopoikilocytosis. Red cell distribution width (RDW) measures anisopoikiloytosis and is readily reported by haematology analysers as a complete blood count parameter. The utility of RDW as a diagnostic marker of haemoglobinopathies in Kenya remains undetermined and undocumented. Objective: This study aimed to determine the diagnostic efficacy of RDW in discriminating haemoglobinopathy and haemoglobinopathy-free cases in Kenya. Methods: The case-control study used randomly selected haematology analyser outputs for haemoglobinopathy-free (241, 49.4%) and haemoglobinopathy cases (247, 50.1%) aged 1 month to 66 years old tested in the Aga Khan Hospital, Kisumu, and its satellite centres in western Kenya from 01 January 2015 to 31 December 2020. Results were verified using high performance liquid chromatography. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of RDW as a biomarker for sickle cell disease (SCD) and sickle cell trait phenotypes and ß-thalassaemia. Results: The RDW showed diagnostic significance in SCD phenotypes at 21.1 ROC curve coordinate with 67.7% sensitivity, 90.0% specificity, 0.789 accuracy, 70.5% positive predictive validity, 88.8% negative predictive validity, 6.77 positive likelihood ratio, 0.36 negative likelihood ratio and 18.94 (11.4-31.4) odds ratio. Conclusion: An RDW of 21.1% is potentially a predictor of SCD haemoglobin phenotypes and should be included in the haematology screening algorithm as a critical value, above which suspected cases qualify to be investigated for SCD.

6.
Int J Burns Trauma ; 12(6): 241-250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36660264

RESUMO

OBJECT: Burn is the major cause of disability in developing countries, and most burn patients have burns involving the upper limbs. Upper limb burns can result in scarring, contractures, and weakness, leading to limitation of wide range of movements and social well-being, hence reducing the quality of life. General objective: To determine the quality of life among patients with burns of the upper limbs at KNRH. METHODS: This cross-sectional study recruited 108 participants of 5 years and above during their first six months post-discharge from Kiruddu National Referral Hospital with burns to upper limbs. Recruitment was consecutive from the burns unit clinic following ethical approval from the School of Medicine Research and Ethics Committee (SOMREC). Participants were given a burn-related QOL questionnaire. Data were then entered into Epidata 4.2 and imported into STATA 15.1 for analysis. Factors associated with poor quality of life were determined by modified Poisson regression to generate prevalence ratios with 95% confidence intervals. RESULTS: A total of 108 participants were recruited for the study; 97 (89.8%) were adults and responded to the adult QOL questionnaire, while the rest were pediatrics. The mean age of the adults was 28 years (SD=8.6), while the median age of the pediatrics was eight years (IQR=6-10), and 61.1% were male. The upper extremity function (physical) quality of life was good, while the social relationship quality of life was poor. The factors associated with poor quality of life were degree (deep) of burns, multiple surgeries, age above 55 years, and being divorced. CONCLUSIONS: There is generally poor upper extremity function or physical QOL among adults and children, while there is generally good social relationship QOL among adults and children.

7.
Mol Cell Neurosci ; 43(1): 60-71, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19286457

RESUMO

A body of evidence points to the matricial CCN proteins as key regulators of organogenesis. NOV/CCN3, a founder CCN member, is expressed in the developing central nervous system but its functions during neural development have not been studied yet. Here we describe the pattern of NOV expression during rat cerebellar postnatal development and show that NOV expression increases during the second postnatal week, a critical period for the maturation of granule neuron precursors (GNP). NOV transcripts are specifically produced by Purkinje neurons and NOV protein localises extracellularly in the molecular layer and the inner part of the external granule layer, at a key position to control GNP proliferation and migration. In vitro, NOV reduces Sonic Hedgehog-induced GNP proliferation through beta3 integrins and stimulation of GSK3-beta activity whereas NOV stimulates GNP migration through distinct RGD-dependent integrins. These findings identify a new paracrine role of NOV in the development of cerebellar granule neurons.


Assuntos
Cerebelo/citologia , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Neurônios/fisiologia , Células-Tronco/fisiologia , Animais , Movimento Celular/fisiologia , Proliferação de Células , Células Cultivadas , Cerebelo/crescimento & desenvolvimento , Cerebelo/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Integrina beta3/metabolismo , Proteína Sobre-Expressa em Nefroblastoma/genética , Neurônios/citologia , Oligopeptídeos/metabolismo , Comunicação Parácrina/fisiologia , Células de Purkinje/citologia , Células de Purkinje/fisiologia , Ratos , Ratos Wistar , Células-Tronco/citologia
8.
J Stomatol Oral Maxillofac Surg ; 122(1): 101-106, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32450320

RESUMO

Arthrogryposis multiplex congenita (AMC) is a rare entity gathering many diseases, isolated or included in more global syndromes. It affects symmetrically joints of lower limbs, back and maxillofacial area with temporomandibular joint (TMJ) impairment leading to deterioration of oral functions and mouth opening resulting in poor quality of life. Therapeutic strategy varies according to type and severity of impairment and could involve physical therapy and/or surgery. This article reported a case of AMC followed in our unit and highlighting various maxillo-facial impairments, especially restricted mouth opening and its consequences due to fibrotic TMJ and hypertrophic coronoid processes. We described our therapeutic approach based on surgery and postoperative physical therapy. A stable improvement of mouth opening was obtained, and patient's quality of life was increased. We performed a review of the literature and suggested a therapeutic management of mouth opening limitation in AMC.


Assuntos
Artrogripose , Transtornos da Articulação Temporomandibular , Artrogripose/complicações , Artrogripose/diagnóstico , Artrogripose/terapia , Humanos , Qualidade de Vida , Síndrome , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/terapia
9.
Toxicol Lett ; 348: 85-96, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34044057

RESUMO

The skin epidermis is continuously exposed to external aggressions, including environmental pollution. The cosmetic industry must be able to offer dedicated products to fight the effects of pollutants on the skin. We set up an experimental model that exposed skin explants maintained in culture to a pollutant mixture. This mixture P representing urban pollution was designed on the basis of the French organization 'Air Parif' database. A chamber, called Pollubox®, was built to allow a controlled nebulization of P on the cultured human skin explants. We investigated ultrastructural morphology by transmission electron microscopy of high pressure frozen skin explants. A global transcriptomic analysis indicated that the pollutant mixture was able to induce relevant xenobiotic and antioxidant responses. Modulated detoxifying genes were further investigated by laser micro-dissection coupled to qPCR, and immunochemistry. Both approaches showed that P exposure correlated with overexpression of detoxifying genes and provoked skin physiological alterations down to the stratum basale. The model developed herein might be an efficient tool to study the effects of pollutants on skin as well as a powerful testing method to evaluate the efficacy of cosmetic products against pollution.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição Ambiental/efeitos adversos , Pele/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Transmissão , Receptores de Hidrocarboneto Arílico/fisiologia , Pele/metabolismo , Pele/patologia , Pele/ultraestrutura , Xenobióticos/toxicidade
10.
Trop Anim Health Prod ; 42(7): 1541-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20517646

RESUMO

A cross-sectional study was conducted between January 2007 and February 2008 to estimate seroprevalence of brucellosis and identify risk factors associated with Brucella infections in commercial cattle in three districts of Lusaka province (Chongwe, Luangwa, and Kafue; n = 849) and in one rural district from the Central province (n = 48). A total of 897 serum samples were randomly collected from 55 farms along with animal-level data such as sex, age, and parity. Sera were screened for presence of anti-Brucella antibodies using the Rose Bengal test, and positive samples were confirmed using competitive enzyme-linked immunosorbent assay. At the animal level, seroprevalence was estimated at 7.9% (95% CI = 4.4-11.4%) in the Lusaka province and 18.7% (95% CI = 7.5-29.9%) for Chibombo district. Brucellosis seroprevalence varied according to district, with Chongwe district recording the highest compared to other districts. Seroprevalence also varied according to sex with bulls (n = 96) having higher seroprevalence (12.5%; 95% CI = 3.8-21.1%) compared to females (8.1%; 95% CI = 4.6-11.6). Similarly, seroprevalence varied according to age groups, with the age category 1-4 years recording the highest (10.7%). The study recorded relatively low Brucella seroprevalence in commercial farms in Lusaka, compared to the traditional small-scale farms. We suggest that testing and stamping out of infected animals is likely to improve the situation and significantly reduce the public health risk associated with Brucella infections in animals.


Assuntos
Brucelose Bovina/epidemiologia , Indústria de Laticínios/estatística & dados numéricos , Fatores Etários , Animais , Brucelose Bovina/etiologia , Bovinos/microbiologia , Comércio/estatística & dados numéricos , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Masculino , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Sexuais , Zâmbia/epidemiologia
11.
J Orthop Surg Res ; 15(1): 472, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054780

RESUMO

BACKGROUND: In total knee arthroplasty (TKA) a flexible intramedullary rod can be used to account for sagittal bowing of the distal femur. Although patients report better post-operative functional outcome when the flexible rod was used, it is unknown how the use of the flexible rod affects the placement of the femoral TKA component, and how this relates to activities of daily living. It is expected that the use of the flexible rod will result in a more flexed femoral component, a larger patellar tendon moment arm, and consequently in better functional outcome. The goal of this study is to compare the flexible rod to the standard intramedullary rod in primary TKA in terms of fit of the TKA, functional outcome, and sizing of the femoral component. METHODS: A single-blind randomized controlled trial with two groups (flexible vs standard rod), with patients blinded for group allocation, and 2 years post-operative follow-up. The fit of the TKA is quantified by two parameters: (1) the flexion angle of the TKA in the sagittal plane and (2) the sagittal profile of the distal femur compared between the pre-operative bone and the TKA. Both parameters are calculated in 3D volume images obtained using fluoroscopy. Functional outcome will be measured using (1) the timed Get-up and Go test (2), the stair climbing test (3), knee power output, and (4) patient and clinician reported outcomes. Different parameters will be measured during the TKA procedure to account for the invisibility of cartilage in the 3D volumes and to study if the amount of bone removed during the procedure is affected by group allocation. DISCUSSION: The sagittal fit of TKA is not a standardized outcome measure. We discuss our choice of parameters to define the sagittal fit (i.e., flexion angle and sagittal profile), our choice for the parameters we measure during the TKA procedure to account for the lack of cartilage thickness in fluoroscopy, and our choice for the parameters to study if the amount of bone removed during the procedure is affected by group allocation. Lastly, we discuss the merits of this planned trial. TRIAL REGISTRATION: Netherlands Trial Register, 4888 , registered 30 March 2015. https://www.trialregister.nl/trial/4888.


Assuntos
Artroplastia do Joelho/métodos , Fêmur/cirurgia , Fixadores Internos , Osteoartrite do Joelho/cirurgia , Maleabilidade , Atividades Cotidianas , Adulto , Assistência ao Convalescente , Idoso , Feminino , Humanos , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/psicologia , Avaliação de Resultados da Assistência ao Paciente , Satisfação do Paciente , Recuperação de Função Fisiológica , Fatores de Tempo
12.
Arthroplasty ; 2(1): 28, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-35236443

RESUMO

PURPOSE: Head-neck modularity was introduced into total hip arthroplasty to provide more intraoperative surgical options. However, modularity led to new problems, such as trunnionosis and fractures of the femoral prosthesis neck. The purpose of this study was to identify risk factors for hip neck fractures and to provide recommendations to prevent damage and fractures of the neck. METHODS: A systematic review of the literature was performed according to the PRISMA guidelines. RESULTS: Thirty-three case studies were included. Methodologically, most included studies were of moderate or good quality. The 80 neck fractures included in the review took place, on average, 7 years after stem placement. Male gender, high body weight, obesity, previous revision surgery, mixing components from different manufacturers, use of long skirted heads, cobalt-chromium (large size) heads were identified as potential risk factors. CONCLUSION: Hip neck fractures occur on average 7 years after stem placement. The etiology of hip neck fractures is multifactorial. This review revealed several preventable implant- and surgeon-related risk factors.

13.
Mol Cell Biol ; 19(5): 3506-14, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10207074

RESUMO

The 1-kb DNA fragment upstream of the ardC actin gene of Physarum polycephalum promotes the transcription of a reporter gene either in a transient-plasmid assay or as an integrated copy in an ectopic position, defining this region as the transcriptional promoter of the ardC gene (PardC). Since we mapped an origin of replication activated at the onset of S phase within this same fragment, we examined the pattern of replication of a cassette containing the PardC promoter and the hygromycin phosphotransferase gene, hph, integrated into two different chromosomal sites. In both cases, we show by two-dimensional agarose gel electrophoresis that an efficient, early activated origin coincides with the ectopic PardC fragment. One of the integration sites was a normally late-replicating region. The presence of the ectopic origin converted this late-replicating domain into an early-replicating domain in which replication forks propagate with kinetics indistinguishable from those of the native PardC replicon. This is the first demonstration that initiation sites for DNA replication in Physarum correspond to cis-acting replicator sequences. This work also confirms the close proximity of a replication origin and a promoter, with both functions being located within the 1-kb proximal region of the ardC actin gene. A more precise location of the replication origin with respect to the transcriptional promoter must await the development of a functional autonomously replicating sequence assay in Physarum.


Assuntos
Actinas/genética , Replicação do DNA/genética , Physarum polycephalum/genética , Regiões Promotoras Genéticas/genética , Animais , DNA de Protozoário/genética , Resistência a Medicamentos/genética , Cinética , Plasmídeos/genética , Origem de Replicação/genética , Fase S/genética , Transcrição Gênica , Transformação Genética
14.
Mol Cell Biol ; 16(3): 968-76, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8622700

RESUMO

We analyzed the replication of two unlinked actin genes, ardB and ardC , which are abundantly transcribed in the naturally synchronous plasmodium of the slime mold Physarum polycephalum. Detection and size measurements of single-stranded nascent replication intermediates (RIs) demonstrate that these two genes are concomitantly replicated at the onset of the 3-h S phase and tightly linked to replication origins. Appearance of RIs on neutral-neutral two-dimensional gels at specific time points in early S phase and analysis of their structure confirmed these results and further established that, in both cases, an efficient, site-specific, bidirectional origin of replication is localized within the promoter region of the gene. We also determined similar elongation rates for the divergent replication forks of the ardC gene replicon. Finally, taking advantage of a restriction fragment length polymorphism, we studied allelic replicons and demonstrate similar localizations and a simultaneous firing of allelic replication origins. Computer search revealed a low level of homology between the promoters of ardB and ardC and, most notably, the absence of DNA sequences similar to the yeast autonomously replicating sequence consensus sequence in these Physarum origin regions. Our results with the ardB and ardC actin genes support the model of early replicating origins located within the promoter regions of abundantly transcribed genes in P. polycephalum.


Assuntos
Actinas/genética , Physarum polycephalum/genética , Regiões Promotoras Genéticas/genética , Origem de Replicação , Sequência de Aminoácidos , Animais , Dados de Sequência Molecular , Physarum polycephalum/metabolismo , Polimorfismo de Fragmento de Restrição , Replicon/genética
15.
Bone Joint J ; 99-B(11): 1482-1489, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29092987

RESUMO

AIMS: Positive cultures are not uncommon in cases of revision total knee and hip arthroplasty (TKA and THA) for presumed aseptic causes. The purpose of this study was to assess the incidence of positive intra-operative cultures in presumed aseptic revision of TKA and THA, and to determine whether the presence of intra-operative positive cultures results in inferior survival in such cases. PATIENTS AND METHODS: A retrospective cohort study was assembled with 679 patients undergoing revision knee (340 cases) or hip arthroplasty (339 cases) for presumed aseptic causes. For all patients three or more separate intra-operative cultures were obtained. Patients were diagnosed with a previously unsuspected prosthetic joint infection (PJI) if two or more cultures were positive with the same organism. Records were reviewed for demographic details, pre-operative laboratory results and culture results. The primary outcome measure was infection-free implant survival at two years. RESULTS: The incidence of unsuspected PJI was 27 out of 340 (7.9%) in TKA and 41 out of 339 (12.1%) in THA. Following revision TKA, the rate of infection-free implant survival in patients with an unsuspected PJI was 88% (95% confidence intervals (CI) 60 to 97) at two years compared with 98% (95% CI 94 to 99) in patients without PJI (p = 0.001). After THA, the rate of survival was similar in those with unsuspected PJI (92% (95% CI 73 to 98) at two years) and those without (94% (95% CI 89 to 97), p = 0.31). CONCLUSION: Following revision of TKA and THA for aseptic diagnoses, around 10% of cases were found to have positive cultures. In the knee, such cases had inferior infection-free survival at two years compared with those with negative cultures; there was no difference between the groups following THA. Cite this article: Bone Joint J 2017;99-B:1482-9.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Infecções por Bactérias Gram-Positivas/diagnóstico , Prótese de Quadril/efeitos adversos , Cuidados Intraoperatórios , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Adulto , Idoso , Artroplastia de Quadril/instrumentação , Artroplastia do Joelho/instrumentação , Feminino , Seguimentos , Infecções por Bactérias Gram-Positivas/cirurgia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Propionibacterium acnes/isolamento & purificação , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/cirurgia , Staphylococcus epidermidis/isolamento & purificação
17.
Paediatr Drugs ; 18(6): 443-449, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27612991

RESUMO

INTRODUCTION: Doxapram is used as a third-line treatment for apnea unresponsive to caffeine and continuous positive airway pressure (CPAP) in preterm infants. OBJECTIVES: The objectives of this study were to compare the effects of dosing adjusted for gender and postmenstrual age (PMA) (GrA) versus infants' weight alone (GrW) on doxapram plasma levels, clinical efficacy, and side effects. METHODS: This was a randomized, double-blind study, including premature infants for whom optimized caffeine and CPAP therapy for apnea of prematurity had failed. Failure was defined as the persistence of more than one significant apnea per hour over an 8-h period. Plasma levels of doxapram and ketodoxapram were measured with high-performance liquid chromatography (HPLC) 48 h after the onset of treatment. Dosing aimed to maintain the combined doxapram and ketodoxapram plasma level in the therapeutic range of 1.5-4 mg/l. Infants were followed-up for 4 days after the onset of treatment. RESULTS: A total of 85 infants were included: 46 in GrW (27.7 ± 1.9 weeks' gestational age [GA]), 39 in GrA (27.9 ± 1.4 weeks' GA); available plasma levels showed that 25 of 40 in the GrW group and 27 of 37 in the GrA group had levels within the therapeutic range (p = 0.344). Of note, plasma level variance was significantly higher in GrW for doxapram + ketodoxapram (1.87 vs. 0.89; p = 0.028). Clinical efficacy was better in the GrA group, with a reduction from 32 to 3 of 38 (76 %) infants with significant apnea versus 30 to 5 of 45 (56 %) in the GrW group (p < 0.001). No adverse effects were observed during the study. CONCLUSIONS: Taking gender and PMA into account for doxapram dosing did not significantly increase the number of infants with a plasma level in the therapeutic range. However, it improved plasma level stability and clinical efficacy without adverse effects. ClinicalTrials.gov number: NCT00389909.


Assuntos
Apneia/tratamento farmacológico , Doxapram/administração & dosagem , Medicamentos para o Sistema Respiratório/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Masculino , Estudos Prospectivos
18.
Arch Pediatr ; 23(9): 899-907, 2016 Sep.
Artigo em Francês | MEDLINE | ID: mdl-27451382

RESUMO

INTRODUCTION: Group B streptococcus (GBS) is the most common infectious agent responsible for early-onset bacterial sepsis (EOS) in term newborns. French prevention of perinatal GBS disease guidelines recommend screening for maternal vaginal GBS colonization at the 9th month of pregnancy, and use of intrapartum antibiotic prophylaxis (IAP) in case of detected GBS vaginal colonization. Peripheral bacterial sampling (gastric aspiration, ear, or meconium) and measurement of C-reactive protein (CRP) are performed in asymptomatic newborns in case of infectious risk factors and/or incomplete IAP. OBJECTIVE: The aim of this study was to investigate the relation between a rapid intrapartum screening test for GBS during labor in term parturients and infants developing GBS EOS and in comparison to current recommendations. METHODS: We conducted an observational analytic single-center study, with use of a rapid intrapartum GBS screening test, at Toulouse University Hospital. RESULTS: A total of 1416 mother-newborn dyads were prospectively included between 31/01/2012 and 17/08/2012. Vaginal GBS colonization was found at the 9th month of pregnancy in 148 mothers (10.6 %), and 176 mothers (12.5 %) were screened positively at delivery using intrapartum GBS rapid polymerase chain reaction assay (GBS PCR) (P=0.025). No confirmed neonatal GBS EOS was found. Nine infants had suspected GBS EOS because of a positive peripheral bacterial finding and elevated CRP. In these infants, seven pregnant mothers were GBS-positive with GBS PCR assay during labor, and four women were positive on prenatal culture at the 9th month of pregnancy. The diagnostic values of the two tests highlighted a nonsignificant superiority of intrapartum GBS PCR assay (AUC=0.83 [0.68-0.97] vs. 0.67 [0.50-0.84]), (P=0.057). The negative predictive value was improved with intrapartum PCR assay (negative likelihood ratio [LR]: 0.3 [0.1-0.9] vs. 0.6 [0.4-1.1]). Intrapartum GBS PCR assay provided its best positive predictive value in the absence of complete AIP and without other infectious factors (positive LR: 21.3 [15.4-29.5]). CONCLUSION: These results suggest that the intrapartum GBS PCR assay offers a better predictive value of GBS EOS than the usual vaginal culture swab at the 9th month but requires confirmation by large studies.


Assuntos
Complicações Infecciosas na Gravidez/diagnóstico , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/genética , Vagina/microbiologia , Adulto , DNA Bacteriano/isolamento & purificação , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Trabalho de Parto , Sepse Neonatal/diagnóstico , Sepse Neonatal/microbiologia , Sepse Neonatal/prevenção & controle , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Estudos Prospectivos , Infecções Estreptocócicas/transmissão , Streptococcus agalactiae/isolamento & purificação
19.
Arch Pediatr ; 12(2): 151-5, 2005 Feb.
Artigo em Francês | MEDLINE | ID: mdl-15694538

RESUMO

UNLABELLED: Methylxanthines and doxapram have been used to stimulate breathing and to prevent apnea in preterm infants. The use of doxapram is controversial because the therapeutic index seems to be narrow and short-term adverse effects have been described. OBJECTIVE: To determine the use of doxapram in the French neonatal and intensive care units. METHODS: A structured postal questionnaire was sent to all the 236 neonatology and neonatal intensive care units of level IIa, IIb and III in France. The questionnaires were analysed after four months. RESULTS: Answers were obtained from 159 chiefs of department (67.4%), 102 used doxapram (64.1%). Doxapram was mainly used as a second step, if methylxanthines failed to reduce the frequency of apneic spells (102/159 units, 64.1%). Doxapram was usually administered intravenously (91/102 units, 89.2%). Only 57 respondents (35.8%) did not use doxapram, because they were aware of the potential adverse effects or they did not know the drug. Monitoring of drug plasma concentrations was rarely performed (11/102 services, 10.8%). Nevertheless, there was a significant interest in this monitoring. CONCLUSION: Doxapram is frequently used in France to reduce apnea of prematurity if methylxanthine therapy fails. Further studies are needed to determine safety of doxapram at short and long-term. A multicenter, randomised, double-blinded clinical trial would be interesting to perform, similar to the ongoing caffeine for Apnoea of Prematurity trial (CAP) . The French setting seems appropriate for this kind of study.


Assuntos
Doxapram/uso terapêutico , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Medicamentos para o Sistema Respiratório/uso terapêutico , Apneia/tratamento farmacológico , França , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Recém-Nascido Prematuro
20.
Bone Joint J ; 97-B(3): 329-36, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25737516

RESUMO

An increased tibial tubercle-trochlear groove (TT-TG) distance is related to patellar maltracking and instability. Tibial tubercle transfer is a common treatment option for these patients with good short-term results, although the results can deteriorate over time owing to the progression of osteoarthritis. We present a ten-year follow-up study of a self-centring tibial tubercle osteotomy in 60 knees, 30 with maltracking and 30 with patellar instability. Inclusion criteria were a TT-TG ≥ 15 mm and symptoms for > one year. One patient (one knee) was lost to follow-up and one required total knee arthroplasty because of progressive osteoarthritis. Further patellar dislocations occurred in three knees, all in the instability group, one of which required further surgery. The mean visual analogue scores for pain, and Lysholm and Kujala scores improved significantly and were maintained at the final follow-up (repeated measures, p = 0.000, intergroup differences p = 0.449). Signs of maltracking were found in only a minority of patients, with no difference between groups (p > 0.05). An increase in patellofemoral osteoarthritis was seen in 16 knees (31%) with a maximum of grade 2 on the Kellgren-Lawrence scale. The mean increase in grades was 0.31 (0 to 2) and 0.41 (0 to 2) in the maltracking and instability groups respectively (p = 0.2285) This self-centring tibial tubercle osteotomy provides good results at ten years' follow-up without inducing progressive osteoarthritis.


Assuntos
Luxações Articulares/cirurgia , Instabilidade Articular/cirurgia , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Tíbia/cirurgia , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/fisiopatologia , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/fisiopatologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Radiografia , Tíbia/diagnóstico por imagem , Tíbia/fisiopatologia , Resultado do Tratamento
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