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1.
J Tissue Viability ; 30(1): 78-88, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32839066

RESUMO

BACKGROUND: A holistic profile that includes demographic, medical history and wound characteristics of individuals with venous leg ulceration is lacking. Lack of such a profile negatively impacts the ability to develop interventions to improve patient outcomes. OBJECTIVES: To describe the profile of the patient population with venous leg ulceration from published observational (non-interventional) studies and to identify gaps in the knowledge base for future research in this area. METHODS: A systematic review of observational studies that included more than 50 patients, from any world region, of any age and in any care setting. RESULTS: twenty studies, involving 3395 patients, from all world regions met our criteria. Demographic characteristics were well reported and showed a female to male ratio of 1.2:1, average age of 47-65 years, high levels of co-morbidities including hypertension (53-71%) and diabetes (16-20%), and only one study reporting ethnicity. When reported, approximately 4-30% had high levels of depression. The average wound size was 18.6-43.39 cm2; mean wound duration was 13.8-65.5 months, mean number of recurrences was four. No study reported on demographic factors plus medical history plus wound characteristics together. CONCLUSION: a comprehensive, holistic profile of the population with VLU is lacking. There is a critical need for more comprehensive profiling to enable the development of targeted interventions to improve outcomes.


Assuntos
Úlcera da Perna/classificação , Úlcera Varicosa/classificação , Idoso , Feminino , Humanos , Úlcera da Perna/epidemiologia , Masculino , Pessoa de Meia-Idade , Úlcera Varicosa/epidemiologia
2.
Ir Med J ; 111(3): 714, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30376232

RESUMO

Type 1 diabetes (T1D) symptoms are subtle and easily overlooked. Delayed diagnosis can result in Diabetic ketoacidosis (DKA), a life threatening complication with lasting consequences. We sought to define the presenting features of T1D and DKA frequency, in children <15 years diagnosed in a single national tertiary centre, and identify predictive factors for DKA. A review of T1D incident cases was undertaken from 2008-2012 using the National Diabetes Register (ICDNR) and clinical case notes. Data were compared with a 1997/8 national study. We found DKA at presentation in 28.7 % of children and 15.5% had moderate/severe DKA. Commonest symptoms were polydipsia, polyuria, weight loss, and lethargy. Median symptom duration was 17 days. Clinical presentation was similar and frequency of DKA at T1D diagnosis remains high. The proportion with moderate/severe DKA is lower than the 25% previously reported (p=0.038). National monitoring and targeted action to reduce DKA at diagnosis is required.


Assuntos
Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/epidemiologia , Adolescente , Criança , Pré-Escolar , Diagnóstico Tardio , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/fisiopatologia , Feminino , Humanos , Incidência , Lactente , Irlanda/epidemiologia , Masculino , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
3.
Ir Med J ; 107(9): 278-81, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25417386

RESUMO

The incidence of Type 1 diabetes (T1D) in childhood and adolescence is increasing globally with few exceptions. To date limited conflicting data has been available regarding diabetes epidemiology in Ireland. We sought to determine the incidence of T1D in those aged under 15 years in the ROI by establishing a prospective national register of incident cases (Irish Childhood Diabetes National Registry (ICDNR)) using a standardised protocol which includes a measure of case ascertainment using capture-recapture methodology. In the period, 489 new cases were identified. All paediatric centres nationally participated. The directly standardised incidence rate was 27.5 per 100,000 per year (95% CIs: 24.0, 30.9) and 26.0 (95% CIs: 22.7, 29.3) in 2008 and 2009 respectively. The ICDNR is widely acceptable, it has confirmed a high incidence of T1D and is vital to monitor changes in disease incidence, optimise resource utilisation and diabetes management in the Irish population.


Assuntos
Diabetes Mellitus Tipo 1 , Adolescente , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Irlanda/epidemiologia , Masculino , Sistema de Registros
4.
Child Care Health Dev ; 39(2): 202-12, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22168816

RESUMO

OBJECTIVE: We wished to ascertain if there is an association between symptoms of attention-deficit/hyperactivity disorder (ADHD) and home environment in children with ADHD and non-ADHD siblings, controlling for other environmental measures. METHODS: 96 children with ADHD combined type (ADHD-CT) and their siblings participated in the study. Parent and teacher Conners' rating scales were completed and home environment was assessed using the middle childhood and early adolescent Home Observation for Measurement of the Environment (HOME). ADHD symptoms were assessed for correlation with HOME in children with ADHD-CT and non-ADHD siblings and multiple regression analysis was used to control for gender, socio-economic status, exposure to nicotine, exposure to alcohol in utero, birth weight, gestational age, pregnancy and perinatal risk factors. The presence of oppositional disorders was assessed for association with HOME score in those with ADHD-CT. The multiple regression analysis was repeated controlling for environmental factors and for oppositional disorders in those with ADHD-CT. Oppositional symptoms were assessed for correlation with HOME score in non-ADHD siblings. RESULTS: Teacher-rated hyperactive/impulsive scores correlated with HOME (r=-0.27, P < 0.01) in children with ADHD-CT. This association remained significant when other environmental factors and oppositional disorders were controlled for. Environmental factors and gender contributed to 30% of the variance of ADHD symptoms in ADHD-CT. Parent-rated hyperactive/impulsive scores also correlated with HOME (r=-0.28, P < 0.05) for non-ADHD siblings. An association between HOME and diagnosis of oppositional defiant disorder or conduct disorder was found for children with ADHD-CT and between HOME and oppositional symptoms in non-ADHD siblings. CONCLUSIONS: The home environment has a small but significant association with hyperactive/impulsive symptoms in children with ADHD-CT and non-ADHD siblings. This association remained when other environmental factors were taken into account. Oppositional symptoms are associated with home environment in ADHD-CT and in non-ADHD siblings.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Meio Ambiente , Saúde da Família , Hipercinese/epidemiologia , Comportamento Impulsivo/epidemiologia , Irmãos/psicologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/etiologia , Criança , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores Sexuais , Classe Social , Meio Social
5.
Ir Med J ; 105(4): 105-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22708221

RESUMO

A population based case control study was conducted to examine alcohol consumption and maternal smoking during pregnancy and the risk of SIDS in an Irish population. Each SIDS case (n = 287) was compared with control infants (n = 832) matched for date and place of birth for infants born from 1994 to 2001. Conditional logistic regression was used to investigate differences between Cases and Controls establishing Odds Ratio's (OR) and 95% Confidence Intervals (CI). Mothers who smoked were 3 times more likely to have a SIDS Case, and a dose response effect was apparent, with mothers smoking 1-10 cigarettes/day OR 2.93 (CI 1.50-5.71), and those smoking > 10 cigarettes/day OR 4.36 (CI 2.50-7.61). More Case mothers consumed alcohol during pregnancy than Control mothers and, within drinkers, the amount of alcohol consumed was also greater (p < 0.05). A dose response with frequency of drinking was apparent. The adjusted odds ratio for those consuming alcohol in all three trimesters was 3.59 (CI:1.40-9.20). Both of these risk factors are modifiable and need to be incorporated into antenatal education from a SIDS point of view.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Fumar/epidemiologia , Morte Súbita do Lactente/epidemiologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Gravidez , Fatores de Risco
6.
J Pediatr Endocrinol Metab ; 21(2): 155-63, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18422028

RESUMO

UNLABELLED: Thyroid dysfunction is more common in individuals with Down's syndrome (DS) than in the general population, whose clinical features can mask the presenting signs and symptoms of hypothyroidism. Biochemical screening is necessary; however, venepuncture may be difficult. AIMS: To assess the prevalence of thyroid dysfunction in children and adolescents with DS and the feasibility of screening for hypothyroidism using capillary dried blood spot thyroid stimulating hormone (TSH) from infancy. METHODS: 394 children (217 boys, 177 girls) were clinically assessed for thyroid dysfunction and 305 children (aged 4 months to 18.9 years) were screened for hypothyroidism by capillary whole blood TSH sample. RESULTS: Thyroid dysfunction was detected in 4.6%, with 50% unscreened since neonatal screening. Parents reported minimal distress by fingerprick screening. CONCLUSION: DS is associated with an increased prevalence of thyroid dysfunction, particularly in preschool children. Biochemical screening is essential and capillary whole blood TSH sampling for hypothyroidism is feasible, less invasive and acceptable.


Assuntos
Síndrome de Down/complicações , Hipotireoidismo/etiologia , Tireotropina/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Lactente , Masculino , Testes de Função Tireóidea
7.
JIMD Rep ; 40: 71-76, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29030855

RESUMO

Adherence to dietary and treatment recommendations is a long-standing concern for adults and adolescents with PKU and treating clinicians. In about 20-30% of PKU patients, Phe levels may be controlled by tetrahydrobiopterin (BH4) therapy. The European PKU 2017 Guidelines recommends treatment with BH4 for cases of proven long-term BH4 responsiveness, with a recommended dosage of Sapropterin 10-20 mg/kg/day.We report four young Irish patients with mild PKU, known to be BH4 responsive, who were treated with lower doses of Sapropterin for over 7 years.Case 1: Female, currently age 20. Genotype p. 165T/p/F39L, c.[194T>C]; [117C>G]. Newborn Phe: 851 µmol/L. Pre-Sapropterin Phe tolerance: 600 mg Phe/day to maintain Phe levels <400 µmol/L. Commenced on Sapropterin 400 mg (6.5 mg/kg/day) with increase in Phe tolerance to 800 mg/day.Case 2: Female, currently age 23. Genotype p. 165T/pF39L; c.[194T>C]; [117C>G]. Newborn Phe: 714 µmol/L. Pre-Sapropterin Phe tolerance: 700 mg Phe/day. Commenced on Sapropterin 400 mg (8 mg/kg/day) with increase in Phe tolerance to 800 mg/day.Case 3: Male, currently age 22. Genotype p. 165T/p.S349P; c.[194T>C][1045T>C]. Newborn Phe: 1,036 µmol/L. Pre-Sapropterin Phe tolerance: 600 mg Phe/day. Commenced on Sapropterin 400 mg (5.4 mg/kg/day). Increased to 1,600 mg Phe/day.Case 4: Female, currently age 29. Genotype p.R408W/p/p.Y414C; c.[1222C>T], [1241A>G]. Newborn Phe: 1,600 µmol/L. Pre-Sapropterin tolerance: 450 mg/day. Commenced on Sapropterin 400 mg (5.0 mg/kg/day). Increased to 900 mg Phe/day.Almost 7 years of surveillance for these four patients has shown that this dose of Sapropterin (range 5-8 mg/kg day) was well tolerated and effective with a significant response to treatment and a marked improvement in quality of life at these lower Sapropterin doses.

8.
J Med Genet ; 43(9): 729-34, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16611748

RESUMO

OBJECTIVE: To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. METHODS: Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. RESULTS: Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett-like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto-temporal predominance and high amplitudes. CONCLUSIONS: The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome. Analysis should be considered in these patients in the clinical setting.


Assuntos
Deficiência Intelectual/genética , Mutação/genética , Proteínas Serina-Treonina Quinases/genética , Convulsões/epidemiologia , Convulsões/genética , Espasmos Infantis/genética , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
9.
Disabil Rehabil ; 28(15): 937-41, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16861201

RESUMO

PURPOSE: To establish the concurrent validity and time to complete of the Stroke Activity Scale (SAS) a recently developed stroke motor disability scale designed for use in a busy clinical setting. METHOD: Forty-one stroke patients with residual hemiplegia were recruited and assessed on a single occasion using both the SAS (five items) and modified Motor Assessment Scale (MMAS) (eight items) by a research physiotherapist. Performance was videotaped and assessed subsequently by a second physiotherapist. RESULTS: Pearson's correlation coefficient between the two measures was 0.91. The SAS was significantly quicker to complete than the MMAS (2.8 vs. 10.4 min, p < 0.0001). CONCLUSION: The SAS had high concurrent validity with the MMAS but was much quicker to complete and therefore more suitable for use in clinical environments where time is at a premium.


Assuntos
Avaliação da Deficiência , Hemiplegia/fisiopatologia , Atividade Motora , Acidente Vascular Cerebral/fisiopatologia , Atividades Cotidianas , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
10.
Cancer Res ; 51(12): 3296-303, 1991 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-1674898

RESUMO

Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P less than 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Proteínas Proto-Oncogênicas/análise , Proto-Oncogenes , Receptores de Estrogênio/análise , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Linfonodos/patologia , Metástase Linfática , Menopausa , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Receptor ErbB-2
11.
Biochim Biophys Acta ; 551(1): 207-19, 1979 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-311657

RESUMO

Na+, K+ and Cl- concentrations (cij) and activities (aij), and mucosal membrane potentials (Em) were measured in epithelial cells of isolated bullfrog (Rana catesbeiana) small intestine. Segments of intestine were stripped of their external muscle layers, and bathed (at 25 degrees C and pH 7.2) in oxygenated Ringer solutions containing 105 mM Na+ and Cl- and 5.4 mM K+. Na+ and K+ concentrations were determined by atomic absorption spectrometry and Cl- concentrations by conductometric titration following extraction of the dried tissue with 0.1 M HNO3. 14C-labelled inulin was used to determine extracellular volume. Em was measured with conventional open tip microelectrodes, aiCl with solid-state Cl-selective silver microelectrodes and aiNa and aiK with Na+ and K+-selective liquid ion-exchanger microelectrodes. The average Em recorded was -34mV. ciNa, ciK and ciCl were 51, 105 and 52 mM. The corresponding values for aiNa, aiK and aiCl were 18, 80 and 33 mM. These results suggest that a large fraction of the cytoplasmic Na+ is 'bound' or sequestered in an osmotically inactive form, that all, or virtually all the cytoplasmic K+ behaves as if in free solution, and that there is probably some binding of cytoplasmic Cl-. aiCl significantly exceeds the level corresponding to electrochemical equilibrium across the mucosal and baso-lateral cell membranes. Earlier studies showed that coupled mucosal entry of Na+ and Cl- is implicated in intracellular Cl- accumulation in this tissue. This study permitted estimation of the steady-state transapical Na+ and Cl- electrochemical potential differences (deltamuNa and deltamuCl). deltamuNa (-7000 J . mol-1; cell minus mucosal medium) was energetically more than sufficient to account for deltamuCl (1000--2000 J . mol-1).


Assuntos
Cloretos/metabolismo , Intestino Delgado/metabolismo , Sódio/metabolismo , Animais , Transporte Biológico Ativo , Epitélio/metabolismo , Mucosa Intestinal/metabolismo , Cinética , Potássio/metabolismo , Rana catesbeiana
12.
Ir Med J ; 98(6): 172, 174-5, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16097508

RESUMO

An accurate assessment of stroke severity and the ability to predict prognosis is important for determining rehabilitation needs and long term management of patients after stroke. The Orpington Prognostic Score (OPS) is a clinically derived stroke severity scale that can be used to stratify patients into different severity groups. The aim of this study was to validate the Orpington Prognostic Score (OPS) in an Irish in-patient stroke population. Fifty 'first stroke' patients (21 male, median age 72.5 [range 31-93] years) were assessed within two weeks following stroke onset. Subjects were stratified into mild, moderate and severe groups using previously established cut-offs for the OPS. Outcomes were determined prospectively and compared to initial severity groups. Patients in the severe group had a significantly increased chance of dying (Odds ratio [95%CI] 2.16 [1.72-2.72] and this persisted after adjustment for age and gender. Length of stay increased significantly with increasing stroke severity group (F ratio 7.0 p=0.0025) and this association remained after adjusting for age and gender. The odds of being discharged home or of being able to walk independently by time of discharge decreased significantly (all p<0.001) as stroke severity increased and adjusting for age and gender did not alter these associations. A higher OPS score within 2 weeks of stroke onset was significantly associated with longer length of stay, increased mortality, reduced mobility at discharge and a reduced likelihood of discharge home. The OPS is a valid measure of stroke severity in Irish stroke in-patients.


Assuntos
Avaliação da Deficiência , Pacientes Internados , Reabilitação do Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Acidente Vascular Cerebral/mortalidade
13.
Ir Med J ; 98(2): 48-52, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15835512

RESUMO

Down syndrome (DS) is the most common chromosomal cause of developmental disability in Ireland. Children with DS have a high incidence of associated treatable medical disorders where early intervention carries a better outcome. Currently there are no agreed protocols for the screening and management of children and adults with DS in Ireland. A cross-sectional study of 394 children and adolescents was undertaken in the Eastern Regional Health Authority (ERHA) to assess the medical needs of children and adolescents with DS, in order to develop medical management guidelines. This study provides evidence-based data that children and adolescents with DS have a high incidence of treatable medical disorders, which supports the need for the medical management guidelines presented.


Assuntos
Síndrome de Down/complicações , Adolescente , Estatura , Vértebras Cervicais/fisiopatologia , Criança , Estudos Transversais , Transtornos da Audição , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Humanos , Irlanda , Instabilidade Articular/diagnóstico , Instabilidade Articular/fisiopatologia , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/diagnóstico , Transtornos da Visão
14.
Clin Infect Dis ; 39(2): 173-8, 2004 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-15307025

RESUMO

Ocular toxocariasis in humans is typically a unilateral disease caused by second-stage larvae of the Toxocara species. Serological evidence of widespread infection in humans provides little information on clinical disease. There is only a single previous estimate of the prevalence of ocular toxocariasis (from Alabama). The present survey examined the extent of consultant-diagnosed toxocaral eye disease among a population of schoolchildren. More than 120,000 participants were surveyed by questionnaire and follow-up. Two sets of control subjects from the same school and from the same county were compared with persons who had ocular toxocariasis. The prevalence of consultant-diagnosed toxocaral eye disease was 6.6 cases per 100,000 persons when only cases regarded as definite by the consultant ophthalmologist were included. This increased to 9.7 cases per 100,000 persons when both definite and strongly suspected cases were included. Geophagia and a history of convulsion were associated with toxocaral eye disease in both of the case-control studies.


Assuntos
Infecções Oculares Parasitárias/epidemiologia , Toxocaríase/epidemiologia , Adolescente , Adulto , Fatores Etários , Animais , Animais Domésticos , Estudos de Casos e Controles , Criança , Pré-Escolar , Cães , Infecções Oculares Parasitárias/complicações , Feminino , Humanos , Irlanda/epidemiologia , Masculino , Pica/complicações , Prevalência , Sons Respiratórios , Fatores de Risco , Convulsões/complicações , Toxocaríase/complicações
15.
J Cereb Blood Flow Metab ; 8(5): 733-41, 1988 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3262116

RESUMO

The effects of the adenosine deaminase inhibitor, deoxycoformycin, on purine release from the rat cerebral cortex were studied with the cortical cup technique. Deoxycoformycin (5 and 500 micrograms/kg i.v.) enhanced the hypoxia/ischemia-evoked release of adenosine from the cerebral cortex, indicating a marked rise in the adenosine content of interstitial fluid in the cerebral cortex. Inosine and hypoxanthine release were attenuated at the higher dose of deoxycoformycin. Uric acid release into the cortical perfusates was enhanced at the higher dose level. These results demonstrate that low doses of deoxycoformycin can be used to elevate interstitial levels of adenosine in the brain during hypoxia, and to depress the formation of some of its metabolites. The elevation of hypoxia/ischemia-evoked adenosine levels can account for the previously reported potentiation of hypoxia-evoked increases in rat cerebral blood flow after deoxycoformycin administration. The potential therapeutic utility of these findings is discussed.


Assuntos
Córtex Cerebral/metabolismo , Coformicina/farmacologia , Hipóxia/metabolismo , Ribonucleosídeos/farmacologia , Adenosina/metabolismo , Animais , Córtex Cerebral/efeitos dos fármacos , Coformicina/análogos & derivados , Hipoxantina , Hipoxantinas/metabolismo , Inosina/metabolismo , Masculino , Pentostatina , Ratos , Ratos Endogâmicos , Ácido Úrico/metabolismo , Xantina , Xantinas/metabolismo
16.
J Cereb Blood Flow Metab ; 8(2): 179-85, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3343292

RESUMO

The cerebral cortical cup technique has been used to study the effects of nifedipine and felodipine on adenosine and inosine release from the rat brain. After basal and hypoxia (8% 02)-evoked control levels of purine release had been established, these 1,4-dihydropyridine calcium antagonists were administered intraperitoneally (1 mg/kg). Both agents depressed basal levels of purine efflux and suppressed the hypoxia-evoked release of adenosine and inosine. An inhibition of the transporter that mediates purine efflux from brain cells is likely to account for the suppression of release from the cerebral cortex. A reduced release of adenosine into the interstitial space also explains the ability of both agents to block the increase in CBF evoked by hypoxic challenges.


Assuntos
Adenosina/metabolismo , Córtex Cerebral/metabolismo , Hipóxia Encefálica/metabolismo , Inosina/metabolismo , Nifedipino/farmacologia , Nitrendipino/análogos & derivados , Animais , Felodipino , Masculino , Nitrendipino/farmacologia , Ratos , Ratos Endogâmicos
17.
J Cereb Blood Flow Metab ; 7(6): 679-86, 1987 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3693425

RESUMO

The cerebral cortical cup technique was used to monitor changes in adenosine and inosine levels in the rat cerebral cortex during periods of hypoxia, anoxia, or hemorrhagic hypotension. Basal levels of adenosine and inosine in cortical perfusates stabilized within 10 min at concentrations of 30-50 and 75-130 nM, respectively. Comparable levels were observed in normal CSF collected from the cisterna magna. Reductions in the oxygen content of the inspired air (14, 12, 8, and 5% oxygen) resulted in increases in the adenosine and inosine levels in the cortical perfusates, the magnitude of the increase being progressively more pronounced with greater reductions in the oxygen content. Cerebral anoxia/ischemia, induced by 100% nitrogen inhalation, caused a rapid increase in the adenosine and inosine contents of the cortical perfusates. Hemorrhagic hypotension (46.1 +/- 1.7 mm Hg) of 5 min duration did not result in an elevated adenosine or inosine release. The results suggest that interstitial fluid adenosine levels are likely to be in the low nM range in the normoxic animal and are capable of rapid increases during hypoxic or anoxic episodes. The findings support the adenosine hypothesis of CBF regulation.


Assuntos
Adenosina/metabolismo , Córtex Cerebral/metabolismo , Hipóxia/metabolismo , Inosina/metabolismo , Adenosina/líquido cefalorraquidiano , Animais , Hipotensão/etiologia , Hipotensão/metabolismo , Hipóxia/complicações , Inosina/líquido cefalorraquidiano , Masculino , Ratos , Ratos Endogâmicos
18.
Gene ; 83(2): 243-9, 1989 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-2555267

RESUMO

To gain insight into the role of cyclic AMP (cAMP) in Gram-negative soil bacteria, we have studied the expression of an adenyl cyclase-encoding gene 'cya' of Rhizobium meliloti F34. In both Escherichia coli and Bradyrhizobium japonicum, the gene is expressed from a promoter(s) contained on a 2.6-kb fragment of the cloned insert, which may indicate the presence of a functional 'cya' promoter or the coincidental presence of sequences which can function as promoters in these two species. The study of 'cya'-lac fusion activity in R. meliloti indicated that the 'cya' gene is not expressed at detectable levels and, thus, may not contribute to the modulation of cAMP levels under the growth conditions employed. R. meliloti strains carrying defined genomic mutations at the 'cya' locus were still capable of the synthesis of near wild-type levels of cAMP. These results suggest that the cloned 'cya' gene is not the key determinant responsible for cAMP synthesis under the culture conditions employed.


Assuntos
Adenilil Ciclases/genética , Expressão Gênica , Genes Bacterianos , Rhizobium/genética , Clonagem Molecular , AMP Cíclico/metabolismo , Escherichia coli/genética , Genótipo , Família Multigênica , Mutação , Plasmídeos , Mapeamento por Restrição , Rhizobium/enzimologia
19.
Gene ; 77(2): 237-51, 1989 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-2666264

RESUMO

As a first step in determining the importance of the anaplerotic function of phosphoenolpyruvate carboxylase (PEPC) in amino acid biosynthesis, the ppc gene coding for PEPC of Corynebacterium glutamicum ATCC13032 has been cloned by complementation of an Escherichia coli ppc mutant strain. PEPC activity encoded by the cloned gene is not affected by acetyl-CoA under conditions where the E. coli enzyme is strongly activated, whereas acetyl-CoA is able to relieve inhibition by L-aspartate used singly or in combination with alpha-ketoglutarate. Amplification of the ppc gene in a C. glutamicum lysine-excreting strain resulted in increased PEPC-specific activity and lysine productivity. The nucleotide sequence of a DNA fragment of 4885 bp encompassing the ppc gene has been determined. At the amino acid level, PEPC from C. glutamicum presents overall a high degree of similarity with corresponding enzymes from three different organisms. The location of some strictly conserved regions may have important implications for PEPC activity and allostery.


Assuntos
Carboxiliases/genética , Clonagem Molecular , Corynebacterium/genética , Genes Bacterianos , Fosfoenolpiruvato Carboxilase/genética , Sequência de Aminoácidos , Sequência de Bases , Southern Blotting , Códon , Corynebacterium/enzimologia , DNA Bacteriano/genética , Escherichia coli/enzimologia , Escherichia coli/genética , Dados de Sequência Molecular , Fosfoenolpiruvato Carboxilase/biossíntese , Fosfoenolpiruvato Carboxilase/metabolismo , Mapeamento por Restrição , Transformação Bacteriana
20.
Gene ; 278(1-2): 107-14, 2001 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-11707327

RESUMO

The organization of the alginate gene cluster in Pseudomonas fluorescens was characterized. A bank of genomic DNA from P. fluorescens was mobilized to a strain of Pseudomonas aeruginosa with a transposon insertion (algJ::Tn501) in the alginate biosynthetic operon that rendered it non-mucoid. Phenotypic complementation in this heterologous host was observed, and a complementing clone containing 32 kb of P. fluorescens DNA was obtained. Southern hybridization studies showed that genes involved in alginate biosynthesis (e.g. algD, algG, and algA) were approximately in the same order and position as in P. aeruginosa. When the clone was mobilized to a P. aeruginosa algG mutant that produced alginate as polymannuronate due to its C5-epimerase defect, complementation was observed and the alginate from the recombinant strain contained L-guluronate as determined by proton nuclear magnetic resonance spectroscopy. A sequence analysis of the P. fluorescens DNA containing algG revealed sequences similar to P. aeruginosa algG that were also flanked by algE- and algX-like sequences. The predicted AlgG amino acid sequence of P. fluorescens was 67% identical (80% similar) to P. aeruginosa AlgG and 60% identical (76% similar) to Azotobacter vinelandii AlgG. As in P. aeruginosa, AlgG from P. fluorescens appeared to have a signal sequence that would localize it to the periplasm where AlgG presumably acts as a C5-epimerase at the polymer level. Non-polar algG knockout mutants of P. fluorescens were defective in alginate production, suggesting a potential role for this protein in polymer formation.


Assuntos
Alginatos/metabolismo , Carboidratos Epimerases/genética , Família Multigênica/genética , Pseudomonas fluorescens/genética , Sequência de Aminoácidos , Sequência de Bases , Carboidratos Epimerases/metabolismo , Divisão Celular/genética , Clonagem Molecular , DNA Bacteriano/química , DNA Bacteriano/genética , Ordem dos Genes , Dados de Sequência Molecular , Mutagênese Insercional , Mutação , Fenótipo , Pseudomonas fluorescens/crescimento & desenvolvimento , Pseudomonas fluorescens/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos
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