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1.
Scand J Rheumatol ; 50(1): 1-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32856510

RESUMO

Objective: Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method: For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results: Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion: Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort.


Assuntos
Artrite Reumatoide/epidemiologia , Progressão da Doença , Índice de Gravidade de Doença , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia
2.
Epidemiol Infect ; 145(8): 1584-1590, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28274291

RESUMO

Giardia duodenalis and Cryptosporidium species are protozoan parasites capable of causing gastrointestinal disease in humans and animals through the ingestion of infective faeces. Whereas Cryptosporidium species can be acquired locally or through foreign travel, there is the mis-conception that giardiasis is considered to be largely travel-associated, which results in differences in laboratory testing algorithms. In order to determine the level of variation in testing criteria and detection methods between diagnostic laboratories for both pathogens across Scotland, an audit was performed. Twenty Scottish diagnostic microbiology laboratories were invited to participate with questions on sample acceptance criteria, testing methods, testing rates and future plans for pathogen detection. Reponses were received from 19 of the 20 laboratories representing each of the 14 territorial Health Boards. Detection methods varied between laboratories with the majority performing microscopy, one using a lateral flow immunochromatographic antigen assay, another using a manually washed plate-based enzyme immunoassay (EIA) and one laboratory trialling a plate-based EIA automated with an EIA plate washer. Whereas all laboratories except one screened every stool for Cryptosporidium species, an important finding was that significant variation in the testing algorithm for detecting Giardia was noted with only four laboratories testing all diagnostic stools. The most common criteria were 'travel history' (11 laboratories) and/or 'when requested' (14 laboratories). Despite only a small proportion of stools being examined in 15 laboratories for Giardia (2%-18% of the total number of stools submitted), of interest is the finding that a higher positivity rate was observed for Giardia than Cryptosporidium in 10 of these 15 laboratories. These findings highlight that the underreporting of Giardia in Scotland is likely based on current selection and testing algorithms.


Assuntos
Auditoria Clínica/normas , Criptosporidiose/diagnóstico , Giardíase/diagnóstico , Cromatografia de Afinidade , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Cryptosporidium/isolamento & purificação , Notificação de Doenças , Giardia/isolamento & purificação , Giardíase/epidemiologia , Giardíase/parasitologia , Humanos , Técnicas Imunoenzimáticas , Escócia/epidemiologia
3.
Epidemiol Infect ; 145(14): 3007-3011, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28879824

RESUMO

Giardiasis is a treatable disease, caused by the flagellated protozoan parasite, Giardia duodenalis (G. duodenalis). It is one of the most common enteric parasites found globally to cause gastrointestinal disturbances, and infections may result in long-term irritable bowel syndrome-like symptoms. It is a common misconception that giardiasis is associated with foreign travel, which results in locally acquired cases in the UK being underdiagnosed. This report highlights the findings from one large Scottish Health Board, arising from a change in testing methodology, which resulted in the screening of all stools submitted for enteric investigations for G. duodenalis. Previous selection criteria were restricted to patients with a travel history to specific regions of the world, or on the basis of certain clinical details. In this report, clinical details were recorded from samples shown to be positive using two methods: an ELISA-based antigen detection assay and microscopy. Clinical details were assessed for a total of 28 laboratory-confirmed positive cases against the original selection criteria. Twenty-six cases (93%) would have been excluded from Giardia testing if the previous selection criteria had been applied. Although nine cases stated foreign travel, only two had been to regions deemed to be 'high risk'. Therefore, those seven cases that travelled to perceived 'low-risk' regions would have been excluded from testing for this reason. This summary highlights the need for significant improvements to the selection criteria for Giardia testing. Laboratories should be encouraged towards the testing of all routinely submitted stools for this neglected pathogen to ensure cases that are acquired locally are properly identified and treated effectively.


Assuntos
Notificação de Doenças/métodos , Giardia lamblia/isolamento & purificação , Giardíase/diagnóstico , Saúde Pública/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Notificação de Doenças/normas , Ensaio de Imunoadsorção Enzimática , Fezes/parasitologia , Feminino , Giardíase/parasitologia , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Escócia , Adulto Jovem
4.
Ann Oncol ; 27(5): 818-27, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26861597

RESUMO

BACKGROUND: Following neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB). PATIENTS AND METHODS: Women with cT1-3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery [Mastectomy (Mast) versus BCS] and post-chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan-Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses. RESULTS: From 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 [hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566-0.939, P = 0.015] and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689-0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS-ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05). CONCLUSIONS: In the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Terapia Neoadjuvante , Radioterapia Adjuvante , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Linfonodos/efeitos da radiação , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
5.
Public Health ; 138: 50-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27091437

RESUMO

OBJECTIVES: Current guidelines support the use of screening for early detection in breast, prostate, colorectal and cervical cancer. The purpose of this study was to evaluate whether insurance status predicts for more advanced disease in these four currently screened cancers. STUDY DESIGN: The Surveillance, Epidemiology, and End Results (SEER) database was queried for breast, prostate, colorectal and cervix in patients aged 18-64 years. The database was queried from 2007 to 2011, with 425,614 patients with known insurance status included. METHODS: Multinomial logistic regression was used to evaluate insurance status and cancer presentation. RESULTS: Under multivariate analysis for breast cancer, uninsured patients more often had invasive disease (odds ratio [OR]: 1.55), T- (OR: 2.00), N- (OR: 1.59) stage, and metastatic disease (OR: 3.48), and were more often high-grade (OR: 1.21). For prostate cancer, uninsured patients again presented more commonly with higher T-stage (OR: 1.45), nodal (OR: 2.90) and metastatic (OR: 4.98) disease, in addition to higher prostate-specific antigen (OR: 2.85) and Gleason score (OR: 1.65). Colorectal cancer had similar findings with uninsured individuals presenting with more invasive disease (OR: 1.78), higher T (OR: 1.86), N (OR: 1.22), and M (OR: 1.58) stage, in addition to higher carcinoembryonic antigen levels (OR: 1.66). Similar results were seen for cervical cancer with uninsured having higher T (OR: 2.03), N (OR: 1.21), and M (OR: 1.45) stage. CONCLUSION: In the four cancers detected by screening exams, those without health insurance present with more advanced disease, with higher stage and grade, and more elevated tumour markers.


Assuntos
Detecção Precoce de Câncer , Disparidades nos Níveis de Saúde , Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Neoplasias/patologia , Adolescente , Adulto , Neoplasias da Mama/patologia , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Estados Unidos , Neoplasias do Colo do Útero/patologia , Adulto Jovem
6.
Epidemiol Infect ; 143(6): 1219-24, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25185671

RESUMO

Cryptosporidium hominis is one of the most prevalent protozoan parasites to infect humans where transmission is via the consumption of infective oocysts. This study describes sporadic cases in addition to the molecular diversity of outbreak cases in Scotland using the glycoprotein-60 subtyping tool. From a total of 187 C. hominis isolates, 65 were subjected to further molecular analysis and 46 were found to be the common IbA10G2 subtype. Unusual subtypes included four isolates belonging to the Ia family (IaA14R3, n = 12; IaA14R2, n = 1; IaA9G3, n = 1; IaA25R3, n = 2), two from the Id family (IdA24, n = 1; IdA17, n = 1) and one belonging to the Ie family, namely IeA11G3T3. These data contribute significantly to our knowledge and understanding of the molecular diversity of C. hominis isolates from outbreak investigations involving Scottish residents which will be beneficial for the management of future outbreaks.


Assuntos
Cryptosporidium/genética , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Surtos de Doenças/estatística & dados numéricos , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Escócia/epidemiologia , Adulto Jovem
7.
Parasitology ; 142(2): 318-25, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25244937

RESUMO

Cryptosporidium parvum (C. parvum) is one of the most prevalent protozoan pathogens responsible for inducing human and animal disease worldwide. In this study, the glycoprotein-60 (gp60) subtyping tool was employed to assess the molecular diversity of C. parvum from human feces throughout Scotland during potential outbreaks. Over a 24-month period, microscopy analysis revealed 1139 positive feces containing Cryptosporidium species with 256 identified by molecular methods specifically as C. parvum. Cryptosporidium parvum was shown to be more prevalent in rural areas of Scotland and subtyping of 87 isolates demonstrated the predominant family as IIa, which occurred in 94% (n=82) of isolates. The IIaA15G1R1 subtype was most common, being isolated from 47% (n=41) of Scottish human cases. Non-IIa strains constituted a total of 5 isolates and included subtypes from the IIc, IId and IIg families. This information contributes significantly to existing knowledge and understanding of C. parvum subtypes in Scotland which is vital in assisting with the management of future local and national outbreaks.


Assuntos
Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Cryptosporidium parvum/genética , Cryptosporidium parvum/isolamento & purificação , Genótipo , Humanos , Escócia/epidemiologia , Estações do Ano , Especificidade da Espécie , Fatores de Tempo
8.
Eur J Clin Microbiol Infect Dis ; 33(3): 305-11, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23995977

RESUMO

In the UK, methicillin-resistant Staphylococcus aureus (MRSA)-associated skin and soft tissue infections (SSTIs) are predominantly managed in the hospital using intravenous (IV) glycopeptides. We set out to explore the potential for and relative healthcare costs of earlier hospital discharge through switch to oral antibiotic therapy (linezolid or rifampicin and doxycycline) or continuation of IV therapy (teicoplanin) via an outpatient parenteral antimicrobial therapy (OPAT) service. Over 16 months, 173 patients were retrospectively identified with MRSA SSTI, of whom 82.8 % were treated with IV therapy. Thirty-seven patients were potentially suitable for earlier discharge with outpatient therapy. The model assumed 3 days of inpatient management and a maximum of 14 days of outpatient therapy. For the status quo, where patients received only inpatient care with IV therapy, hospital costs were calculated at £12,316 per patient, with 97 % of costs accounted for by direct bed day costs. The mean total cost savings achievable through OPAT or oral therapy was estimated to be £6,136 and £6,159 per patient treated, respectively. A significant proportion of patients with MRSA SSTI may be suitable for outpatient management with either oral therapy or via OPAT, with the potential for significant reduction in healthcare costs.


Assuntos
Antibacterianos/economia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/economia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escócia/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Adulto Jovem
10.
J Dairy Sci ; 95(12): 7261-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23040023

RESUMO

Milk urea nitrogen (MUN) is correlated with N balance, N intake, and dietary N content, and thus is a good indicator of proper feeding management with respect to protein. It is commonly used to monitor feeding programs to achieve environmental goals; however, genetic diversity also exists among cows. It was hypothesized that phenotypic diversity among cows could bias feed management decisions when monitoring tools do not consider genetic diversity associated with MUN. The objective of the work was to evaluate the effect of cow and herd variation on MUN. Data from 2 previously published research trials and a field trial were subjected to multivariate regression analyses using a mixed model. Analyses of the research trial data showed that MUN concentrations could be predicted equally well from diet composition, milk yield, and milk components regardless of whether dry matter intake was included in the regression model. This indicated that cow and herd variation could be accurately estimated from field trial data when feed intake was not known. Milk urea N was correlated with dietary protein and neutral detergent fiber content, milk yield, milk protein content, and days in milk for both data sets. Cow was a highly significant determinant of MUN regardless of the data set used, and herd trended to significance for the field trial data. When all other variables were held constant, a percentage unit change in dietary protein concentration resulted in a 1.1mg/dL change in MUN. Least squares means estimates of MUN concentrations across herds ranged from a low of 13.6 mg/dL to a high of 17.3 mg/dL. If the observed MUN for the high herd were caused solely by high crude protein feeding, then the herd would have to reduce dietary protein to a concentration of 12.8% of dry matter to achieve a MUN concentration of 12 mg/dL, likely resulting in lost milk production. If the observed phenotypic variation is due to genetic differences among cows, genetic choices could result in herds that exceed target values for MUN when adhering to best management practices, which is consistent with the trend for differences in MUN among herds.


Assuntos
Bovinos/metabolismo , Leite/química , Ureia/análise , Animais , Dieta/veterinária , Ingestão de Alimentos , Feminino , Lactação/metabolismo , Nitrogênio/análise
11.
Am J Transplant ; 10(10): 2305-12, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20726963

RESUMO

Any use of alcohol in the years following liver transplantation (LTX) approaches 50% of patients transplanted for alcoholic liver disease (ALD). We collected detailed prospective data on alcohol consumption following LTX for ALD to investigate ongoing patterns of use. Using trajectory modeling we identified four distinct alcohol use trajectories. One group had minimal use over time. Two other groups developed early onset moderate-to-heavy consumption and one group developed late onset moderate use. These trajectories demonstrate that alcohol use varies based on timing of onset, quantity and duration. Using discriminant function analysis, we examine characteristics of recipient's pre-LTX alcohol histories and early post-LTX psychological stressors to identify the profile of those at risk for these specific trajectories. We discuss the relevance of these findings to clinical care and preliminarily to outcomes.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
13.
J Hosp Infect ; 98(4): 433-436, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29203448

RESUMO

The emerging pathogenic multidrug-resistant yeast Candida auris is an important source of healthcare-associated infections and of growing global clinical concern. The ability of this organism to survive on surfaces and withstand environmental stressors creates a challenge for eradicating it from hospitals. A panel of C. auris clinical isolates was evaluated on different surface environments against the standard disinfectant sodium hypochlorite and high-level disinfectant peracetic acid. C. auris was shown to selectively tolerate clinically relevant concentrations of sodium hypochlorite and peracetic acid in a surface-dependent manner, which may explain its ability to successfully persist within the hospital environment.


Assuntos
Candida/efeitos dos fármacos , Candida/isolamento & purificação , Desinfetantes/farmacologia , Microbiologia Ambiental , Viabilidade Microbiana/efeitos dos fármacos , Ácido Peracético/farmacologia , Hipoclorito de Sódio/farmacologia , Candida/fisiologia
14.
QJM ; 110(3): 155-161, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27521583

RESUMO

INTRODUCTION: : Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. While the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance, evidence of the effect on outcome following severe infection is lacking. METHODS: : In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following Gram-negative bacteraemia in the 2-year period around implementation. RESULTS: : Introduction of restrictive antibiotic guidelines was associated with a reduction in utilization of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. Approximately 1593 episodes of bacteremia were included in the study. The mortality over 1-year following Gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. CONCLUSION: : Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following Gram-negative bacteraemia. There was a small reduction in one year mortality.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Clostridioides difficile , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Farmacorresistência Bacteriana , Uso de Medicamentos/estatística & dados numéricos , Feminino , Infecções por Bactérias Gram-Negativas/mortalidade , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Escócia/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/mortalidade
15.
Neuroscience ; 138(3): 793-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16310317

RESUMO

Anabolic androgenic steroids are synthetic derivatives of testosterone designed for therapeutic purposes, but now taken predominantly as drugs of abuse. The most common behavioral effects associated with anabolic androgenic steroid use are changes in anxiety, aggression and reproductive behaviors, including the onset of puberty and sexual receptivity. GABAergic circuits in the forebrain underlie these behaviors and are regulated by gonadal steroids. Work from our laboratories has shown that the expression and function of GABA(A) receptors in the rat and mouse forebrain varies between the sexes and across the estrous cycle. We have also shown that there are significant changes in GABA(A) receptor expression that occur with the progression through puberty to adulthood. Because GABAergic systems are both steroid-sensitive and critical for the expression of behaviors altered with anabolic androgenic steroid use, forebrain GABA(A) receptors are an attractive candidate to assess how molecular actions of anabolic androgenic steroids may be translated to known behavioral outcomes. Our studies demonstrate that anabolic androgenic steroids elicit both acute modulation of GABA(A) receptor-mediated currents, as well as chronic regulation of GABA(A) receptor expression and forebrain GABAergic transmission. Because anabolic androgenic steroid use has now become prevalent not only among adolescent boys, but in an increasing number of adolescent girls, we have also been particularly interested in determining age- and sex-specific effects of anabolic androgenic steroids. Our data show that the effects of chronic anabolic androgenic steroid exposure can be greater for adolescent than adult animals and are more marked in females than in males. These data have particularly important implications with respect to studies we have done demonstrating that chronic anabolic androgenic steroid exposure alters the onset of puberty, estrous cyclicity and sexual receptivity.


Assuntos
Anabolizantes/farmacologia , Androgênios/farmacologia , Prosencéfalo/fisiologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/fisiologia , Adolescente , Animais , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Prosencéfalo/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/genética , Transmissão Sináptica/efeitos dos fármacos
16.
J Mol Biol ; 193(3): 571-8, 1987 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-3586031

RESUMO

The solution structure of the 45-residue plant protein, alpha 1-purothionin, is investigated by nuclear magnetic resonance (n.m.r.) spectroscopy. Using a combination of two-dimensional n.m.r. techniques to demonstrate through-bond and through-space (less than 5 A) connectivities, the 1H n.m.r. spectrum of alpha 1-purothionin is assigned in a sequential manner. The secondary structure elements are then delineated on the basis of a qualitative interpretation of short-range nuclear Overhauser effects (NOE) involving the NH, C alpha H and C beta H protons. There are two helices extending from residues 10 to 19 and 23 to 28, two short beta-strands from residues 3 to 5 and 31 to 34 which form a mini anti-parallel beta-sheet, and five turns. In addition, a number of long-range NOE connectivities are assigned and a low resolution tertiary structure is proposed.


Assuntos
Proteínas de Plantas , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos , Espectroscopia de Ressonância Magnética , Conformação Proteica , Soluções
17.
Neuroscience ; 135(2): 533-43, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16112473

RESUMO

Anabolic androgenic steroids are synthetic derivatives of testosterone designed for therapeutic uses, but now taken as drugs of abuse. Potential health risks associated with anabolic androgenic steroid abuse are believed to be higher in adolescents than in adults, but few studies have tested anabolic androgenic steroid effects in adolescent subjects or determined if effects of these steroids differ between females and males. We have studied GABA(A) receptor expression and function in the medial preoptic nucleus of mice chronically treated during adolescence with the anabolic androgenic steroid, 17alpha-methyltestosterone. Three-week treatment did not elicit significant differences the expression of alpha1, alpha2 or alpha5 subunit mRNAs in animals of either sex, although there was a trend toward decreases in all three subunit mRNAs in female mice, which was augmented and attained significance for the alpha2 subunit mRNA in females treated for six weeks. Immunocytochemical analysis revealed that treatment with 17alpha-methyltestosterone for 6 weeks also elicited a significant decrease in the number of alpha2-immunopositive neurons in female subjects. To test if anabolic androgenic steroid treatment also promoted changes in GABA(A) receptor function, spontaneous inhibitory synaptic currents were analyzed in adolescent animals treated for 3-4 weeks. This treatment regimen promoted a significant decrease in spontaneous inhibitory synaptic current frequency in female, but not male mice. Finally, anabolic androgenic steroid treatment was found to have no effect on the numbers of interneurons within the medial preoptic nucleus, as assessed by immunoreactivity for calcium binding proteins, suggesting that the decrease in the frequency of spontaneous inhibitory synaptic currents in female mice does not arise from an anabolic androgenic steroid-induced loss of interneurons. Taken together, our results indicate that chronic exposure to 17alpha-methyltestosterone elicits significant changes in GABAergic transmission in the medial preoptic nucleus of female, but not male, mice effectively enhancing the sexually dimorphic nature of GABAergic transmission in a forebrain region crucial for the expression of aggression and sexual behaviors.


Assuntos
Anabolizantes/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Metiltestosterona/administração & dosagem , Neurônios/fisiologia , Receptores de GABA-A/metabolismo , Caracteres Sexuais , Animais , Animais Recém-Nascidos , Western Blotting/métodos , Calbindina 2 , Calbindinas , Contagem de Células/métodos , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Feminino , Imuno-Histoquímica/métodos , Técnicas In Vitro , Indóis/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Inibição Neural/efeitos da radiação , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp/métodos , Prosencéfalo/citologia , Prosencéfalo/fisiologia , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Mensageiro/biossíntese , Receptores de GABA-A/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteína G de Ligação ao Cálcio S100/metabolismo
18.
Bone Marrow Transplant ; 35(4): 389-95, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15640828

RESUMO

A blinded prospective study was performed to determine whether screening of whole blood using a real-time, panfungal polymerase chain reaction (PCR) technique could predict the development of invasive fungal infection (IFI) in immunocompromised haemato-oncology patients. In all, 78 patients (125 treatment episodes) were screened twice weekly by real-time panfungal PCR using LightCyclertrade mark technology. IFI was documented in 19 treatment episodes (five proven, three probable and 11 possible), and in 12, PCR was sequentially positive. PCR positivity occurred in: 4/5 proven; 2/3 probable; 6/11 possible; and 29/106 with no IFI. In 8/12 with IFI and sequentially positive PCR results, PCR positivity occurred before (median 19.5 days) and in 4/12 (median 10.5 days) after the initiation of empirical antifungal therapy. Based on sequential positive results for proven/probable IFI sensitivity, specificity, positive predictive value and negative predictive value were 75, 70, 15 and 98%, respectively. Real-time panfungal PCR is a sensitive tool for the early diagnosis of IFI in immunocompromised haemato-oncology patients. It may be most useful as a screening method in high-risk patients, either to direct early pre-emptive antifungal therapy or to determine when empirical antifungal therapy can be withheld in patients with antibiotic--resistant neutropenic fever. However, these strategies require further assessment in comparative clinical trials.


Assuntos
DNA Fúngico/sangue , Micoses/diagnóstico , Neoplasias/sangue , Reação em Cadeia da Polimerase , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/sangue , Neoplasias/microbiologia , Neoplasias/terapia , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade
19.
J Hosp Infect ; 91(2): 171-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26184663

RESUMO

BACKGROUND: This article reports a historical outbreak of Salmonella hadar in a maternity setting. The outbreak occurred following admission of an infected index case, with transmission to 11 other individuals over a three-month period in a maternity and neonatal unit. METHODS: Despite rigorous assessment of clinical practices, screening of patients and staff, and review of disinfection and sterilization policies, the outbreak was difficult to control. This possibly reflects the capacity of S. hadar to survive well in the environment, and cause prolonged and asymptomatic carriage with intermittent shedding. FINDINGS: It is likely that the index case was a mother who had contracted infection after eating suspect food. Additionally, infection may have been perpetuated by shared use of tubes of yellow soft paraffin for lubrication of digital rectal thermometers. CONCLUSION: This outbreak emphasizes the difficulties in controlling outbreaks of S. hadar infection in an obstetric/neonatal setting, and also emphasizes the importance of early stool sampling in any patient with diarrhoeal symptoms.


Assuntos
Infecção Hospitalar/epidemiologia , Diarreia/epidemiologia , Surtos de Doenças , Infecções por Salmonella/epidemiologia , Salmonella enterica/isolamento & purificação , Adulto , Derrame de Bactérias , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Infecção Hospitalar/microbiologia , Diarreia/microbiologia , Feminino , Maternidades , Humanos , Recém-Nascido , Controle de Infecções/métodos , Masculino , Salmonella enterica/classificação
20.
J Clin Pathol ; 46(5): 477-8, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8320333

RESUMO

Two cases of transfusion transmitted Yersinia enterocolitica biotype 3, serotype 09 infection occurred in south east Scotland within four months of each other. In one case, a 79 year old man died the day after receiving a unit of red cell concentrate that had been stored for 29 days after donation. In the second case a 78 year old man died three days after transfusion of a unit of red cell concentrate that had been collected 16 days before transfusion. The donors of both units had no symptoms attributed to gastrointestinal infection. Early outdating of blood for transfusion after three weeks of storage is unlikely to eradicate Y enterocolitica associated fatalities from blood transfusion, and alternative methods should be considered.


Assuntos
Bacteriemia/etiologia , Transfusão de Componentes Sanguíneos/efeitos adversos , Preservação de Sangue/métodos , Yersiniose/transmissão , Yersinia enterocolitica , Idoso , Humanos , Masculino , Fatores de Tempo
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