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1.
Acta Diabetol ; 59(4): 563-569, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35034184

RESUMO

AIMS: Diabetes represents a growing public health problem in sub-Saharan Africa, where diabetic retinopathy (DR) is a major cause of permanent visual loss. We reported the results of a remote screening of DR among urbanized Mozambican people with diabetes. METHODS: We retrospectively collected retinal images and clinical characteristics from 536 patients screened for DR in Maputo (Mozambique), over a period of 2 years (2018-2019). Retinal photographs were captured, digitally stored, and scored locally and by an expert ophthalmologist in Italy remotely. RESULTS: The overall prevalence of DR was 29% with sight-threatening forms accounting for 8.1% of that number. Inter-reader agreement between the local and the Italian ophthalmologists was poor (k < 0.2). Patients with DR were older, had a longer duration of disease, worse glycaemic control, and a higher prevalence of comorbidities. In the multivariate logistic regression analysis, HbA1c, diabetes duration, and coronary heart disease (CHD) were associated with DR. CONCLUSION: Prevalence of DR among urbanized Mozambican patients was similar to that observed in Western countries. Telediagnosis might partially overcome the paucity of local ophthalmologists with experience in DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Humanos , Programas de Rastreamento/métodos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Transtornos da Visão
2.
Acta Med Port ; 33(1): 22-30, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31928600

RESUMO

INTRODUCTION: The aim of the study described in this paper is to screen medical curricula in relation to the attention paid to intimate partner violence, by applying a framework derived from the international literature. MATERIAL AND METHODS: We screened curricula of five Mozambican medical schools based on a state-of-the-art intimate partner violence curriculum framework. The latter framework was based on a review of the literature. RESULTS: Few medical schools of Mozambique could be identified addressing intimate partner violence in their curriculum. When tackled, intimate partner violence content is mostly dealt within the context of Obstetrics and Gynaecology, Community Health and Forensic Medicine rotations. Intimate partner violence contents are integrated as stand-alone modules in some specific subjects. In none of the schools, specific teachers teaching intimate partner violence could be identified. No time allocation was specified to address the topic; no teaching and learning strategies could be identified invoking awareness or supporting basic knowledge acquisition; additionally, hardly any information about related assessment methods was found. Only in one medical school was the subject part of the formal curriculum. DISCUSSION: Intimate partner violence content is hardly and inconsistently addressed. The limited intimate partner violence content tracked in the Mozambican medical schools' curricula, mainly addresses violence in general, for instance as identified in Orthopaedics or Surgery contexts and sexual violence in Obstetrics and Gynaecology. The inclusion of elements of intimate partner violence in the curriculum remains restricted, questioning the impact of medical education of future practitioners' competencies. CONCLUSION: Critical changes are needed in medical curricula to match the current epidemiology of intimate partner violence in Mozambique.


Introdução: O objetivo do estudo descrito neste artigo foi o de examinar os currículos de medicina quanto à atenção dada aos conteúdos sobre a Violência Perpretada pelo Parceiro Íntimo em Moçambique, aplicando uma ferramenta de comparação derivada da literatura internacional. Material e Métodos: Examinámos os currículos de cinco escolas médicas moçambicanas com base numa estrutura curricular da Violência Perpretada pelo Parceiro Íntimo de última geração. A ferramenta de comparação foi baseada numa revisão da literatura anterior. Resultados: Poucas escolas de medicina de Moçambique podem ser identificadas abordando a Violência Perpretada pelo Parceiro Íntimo no seu currículo. Se abordada, a Violência Perpretada pelo Parceiro Íntimo é mais tratada no contexto de Ginecologia e Obstetricia, Saúde Comunitária e Medicina legal. Os conteúdos da Violência Perpretada pelo Parceiro Íntimo são integrados como módulos autónomos em algumas disciplinas específicas. Nenhum dos curriculos identificou professores específicos que leccionam Violência Perpretada pelo Parceiro Intimo. Não foi especificada a alocação de tempo para abordar o tópico; estratégias de ensino e aprendizagem, sensibilização e aquisição de conhecimentos básicos; e dificilmente informação sobre métodos de avaliação específicos. Apenas numa escola de medicina, o assunto fazia parte do currículo formal. Discussão: O conteúdo da Violência Perpretada pelo Parceiro Íntimo é dificil e inconsistentemente tratado. O conteúdo limitado da Violência Perpretada pelo Parceiro Íntimo rastreado nos currículos das escolas médicas moçambicanas aborda principalmente a violência em geral, por exemplo, conforme identificado em contextos de ortopedia ou cirurgia e violência sexual em Ginecologia e Obstetrícia. A implementação no currículo permanece restrita, questionando o impacto da educação médica nas competências dos futuros profissionais. Conclusão: São necessárias mudanças críticas nos currículos médicos para corresponder à actual epidemiologia da Violência Perpretada pelo Parceiro Íntimo em Moçambique.


Assuntos
Currículo , Educação Médica , Conhecimentos, Atitudes e Prática em Saúde , Violência por Parceiro Íntimo , Ginecologia/educação , Humanos , Moçambique , Obstetrícia/educação , Faculdades de Medicina
3.
Front Public Health ; 7: 204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396502

RESUMO

Purpose: The researchers aimed to identify the gaps in competencies designed to help medical students to deal with Intimate Partner Violence (IPV) in key Mozambican medical schools curricula. Method: A survey was administered to 3rd and 6th-year medical students (N387), enrolled in five medical schools in Mozambique. The instrument focused on mapping students' perceived mastery of their knowledge, skills, and attitudes related to IPV. Results: In total, 387 medical students (RR 66%) participated in the survey. The overall mean perceived mastery of IPV competence was 36.18 (SD = 24.52) for knowledge, 32.01 (SD = 27.37) for skills, and 43.47 (SD = 27.58) for attitudes. Though 6th-year students reported a significantly higher mastery level, it is still below a mastery-learning benchmark of 80%. Conclusions: Medical students report critically low levels in their mastery of IPV- related competencies. This implies a need for a more comprehensive approach to developing knowledge, skills, and attitudes to deal with the victims of IPV.

4.
Diabetes Ther ; 10(4): 1189-1204, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31102253

RESUMO

The past three decades have seen a quadruple rise in the number of people affected by diabetes mellitus worldwide, with the disease being the ninth major cause of mortality. Type 2 diabetes mellitus (T2DM) often remains undiagnosed for several years due to its asymptomatic nature during the initial stages. In India, 70% of diagnosed diabetes cases remain uncontrolled. Current guidelines endorse the initiation of insulin early in the course of the disease, specifically in patients with HbA1c > 10%, as the use of oral agents alone is unlikely to achieve glycemic targets. Early insulin initiation and optimization of glycemic control using insulin titration algorithms and patient empowerment can facilitate the effective management of uncontrolled diabetes. Early glucose control has sustained benefits in people with diabetes. However, insulin initiation, dose adjustment, and the need to repeatedly assess blood glucose levels are often perplexing for both physicians and patients, and there are misconceptions and concerns regarding its use. Hence, an early transition to insulin and ideal intensification of treatment may aid in delaying the onset of diabetes complications. This opinion statement was formulated by an expert panel on the basis of existing guidelines, clinical experience, and economic and cultural contexts. The statement stresses the timely and appropriate use of basal insulin in T2DM. It focuses on the seven vital Ts-treatment initiation, timing of administration, transportation and storage, technique of administration, targets for titration, tablets, and tools for monitoring.Funding: Sanofi.

5.
Diabetes Res Clin Pract ; 142: 63-73, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29807105

RESUMO

BACKGROUND: Among non-communicable diseases, diabetes represents a growing public health problem in Africa, where diabetes-related needs remain mostly unmet and the disabling features of foot are worsened by hygienic, cultural, and healthcare issues. We aimed to review clinical characteristics, prevalence, and outcomes of patients with diabetic foot ulcer in Africa. METHODS: We searched the literature for cross-sectional and longitudinal studies reporting the characteristics of patients with diabetic foot in African countries, with a particular focus on ulcer prevalence, amputation rate, and mortality. FINDINGS: Fifty-five full-text papers and ten abstracts were retrieved, reporting data from 19 African countries on 56,173 diabetic patients. According to the data collected, the overall prevalence of foot ulcers was 13% and increased over time, especially since 2001. Approximately 15% of patients with foot lesions underwent major amputation and 14.2% died during hospitalization. In patients with diabetic ulcers, insulin therapy was uncommon and neuropathy was the most common predisposing factor, but the prevalence of peripheral arterial disease correlated with amputation rates. Amputation and mortality decreased over time, probably as result of the implementation of screening programs in the last ten years. Mortality was directly related to previous amputation. INTERPRETATION: The diabetic foot disease in Africa is a growing problem and is burden by high rate of in-hospital mortality. Educational interventions and screening programs including evaluation of the vascular status may play a crucial role to counter diabetic foot disease in Africa.


Assuntos
Pé Diabético/epidemiologia , África , Feminino , Humanos , Masculino , Prevalência , Resultado do Tratamento
6.
Acta Trop ; 171: 146-150, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28373036

RESUMO

The resistance of Plasmodium falciparum to anti-malarial drugs continues to challenge malaria control. We assessed the therapeutic efficacy and safety of artemether-lumefantrine (AL), the first-line treatment of uncomplicated P. falciparum malaria, in children under five years of age in Mozambique. We conducted a prospective one-arm study to evaluate the clinical and parasitological efficacy of AL over 28days at four sentinel sites, using the WHO protocol for assessing the efficacy of antimalarial treatment. msp1, msp2 and glurp genes were analysed by DNA polymerase chain reaction (PCR) to differentiate recrudescence from re-infection with malaria parasites. Haemoglobin concentration was recorded at baseline and on days 7, 14 and 28. A total of 349 children with uncomplicated falciparum malaria were recruited at the four sentinel sites. Adequate clinical and parasitological response to AL on day 28 follow-up varied from 96.3% to 100% after correction by PCR. The drug was well tolerated, and no adverse event related to the drug was reported. AL, the current first-line treatment for uncomplicated falciparum malaria in Mozambique, remains highly efficacious at the study sites. Monitoring of the efficacy of the recommended antimalarial drugs should be continued in order to detect any emerging threat to their efficacy. TRIAL REGISTRATION NUMBER: ACTRN12616001680459.


Assuntos
Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Moçambique , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase , Estudos Prospectivos , Recidiva
7.
Malar J ; 13: 309, 2014 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-25108397

RESUMO

BACKGROUND: Mozambique adopted artemisinin-based combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria in the year 2006, and since 2009 artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) have been proposed as alternative first-line treatments. A multicentre study was conducted in five sites across the country to assess the in vivo efficacy and tolerability of these two drugs. METHODS: Children aged six to 59 months with uncomplicated malaria were recruited between June 2011 and January 2012 in five sites across Mozambique (Montepuez, Dondo, Tete, Chokwe, and Manhiça), and treated with AL or ASAQ in a non-randomized study. Follow-up was organized following standard WHO recommendations for in vivo studies, and included daily visits during the three-day-long supervised treatment course, followed by weekly visits up to day 28. The study primary outcome was the day 28 PCR-corrected early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF), and adequate clinical and parasitological response (ACPR). PCR was performed centrally for all cases of recurrent parasitaemia from day 7 onwards to distinguish recrudescence from re-infection. RESULTS: Four-hundred and thirty-nine (AL cohort; five sites) and 261 (ASAQ cohort, three sites) children were recruited to the study. Day 28 PCR-corrected efficacy for AL was 96.0% (335/339; 95% CI: 93.4-97.8), while for ASAQ it was 99.6% (232/233; 95% CI: 97.6-99.9). The majority of recurring parasitaemia cases throughout follow-up were shown to be re-infections by PCR. Both drugs were well tolerated, with the most frequent adverse event being vomiting (AL 4.5% [20/439]; ASAQ 9.6% [25/261]) and no significant events deemed related to the study drugs. CONCLUSION: This study confirms that both AL and ASAQ remain highly efficacious and well tolerated for the treatment of uncomplicated malaria in Mozambican children. Studies such as these should be replicated regularly in the selected surveillance sentinel sites to continuously monitor the efficacy of these drugs and to rapidly detect any potential signs of declining efficacy to ACT, the mainstay of malaria treatment.


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Amodiaquina/efeitos adversos , Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina , Artemisininas/efeitos adversos , Pré-Escolar , Combinação de Medicamentos , Etanolaminas/efeitos adversos , Feminino , Fluorenos/efeitos adversos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Moçambique/epidemiologia , Resultado do Tratamento
8.
Malar J ; 10: 166, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21676264

RESUMO

BACKGROUND: Prozone means false-negative or false-low results in antigen-antibody reactions, due to an excess of either antigen or antibody. The present study prospectively assessed its frequency for malaria rapid diagnostic tests (RDTs) and Plasmodium falciparum samples in an endemic field setting. METHODS: From January to April 2010, blood samples with P. falciparum high parasitaemia (≥ 4% red blood cells infected) were obtained from patients presenting at the Provincial Hospital of Tete (Mozambique). Samples were tested undiluted and 10-fold diluted in saline with a panel of RDTs and results were scored for line intensity (no line visible, faint, weak, medium and strong). Prozone was defined as a sample which showed no visible test line or a faint or weak test line when tested undiluted, and a visible test line of higher intensity when tested 10-fold diluted, as observed by two blinded observers and upon duplicate testing. RESULTS: A total of 873/7,543 (11.6%) samples showed P. falciparum, 92 (10.5%) had high parasitaemia and 76 were available for prozone testing. None of the two Pf-pLDH RDTs, but all six HRP-2 RDTs showed prozone, at frequencies between 6.7% and 38.2%. Negative and faint HRP-2 lines accounted for four (3.8%) and 15 (14.4%) of the 104 prozone results in two RDT brands. For the most affected brand, the proportions of prozone with no visible or faint HRP-2 lines were 10.9% (CI: 5.34-19.08), 1.2% (CI: 0.55-2.10) and 0.1% (CI: 0.06-0.24) among samples with high parasitaemia, all positive samples and all submitted samples respectively. Prozone occurred mainly, but not exclusively, among young children. CONCLUSION: Prozone occurs at different frequency and intensity in HRP-2 RDTs and may decrease diagnostic accuracy in the most affected RDTs.


Assuntos
Técnicas de Laboratório Clínico/métodos , Erros de Diagnóstico/estatística & dados numéricos , Malária Falciparum/diagnóstico , Plasmodium falciparum/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Imunoensaio/métodos , Lactente , Pessoa de Meia-Idade , Moçambique , Adulto Jovem
9.
Malar J ; 8: 74, 2009 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-19383126

RESUMO

BACKGROUND: Protection against clinical malaria episodes is acquired slowly after frequent exposure to malaria parasites. This is reflected by a decrease with increasing age in both parasite density and incidence of clinical episodes. In many settings of stable malaria transmission, the presence of asymptomatic malaria parasite carriers is common and the definition of clinical malaria remains uncertain. METHODS: Between February 2002 and April 2003, a country-wide malaria survey was conducted in 24 districts of Mozambique, aiming to characterize the malaria transmission intensities and to estimate the proportion of fever cases attributable to malaria infections in order to establish the malaria case definition. A total of 8,816 children less than ten years of age were selected for the study. Axillary temperature was measured in all participating subjects and finger prick blood collections were taken to prepare thick and thin films for identification of parasite species and determination of parasite density. The proportion of fever cases attributable to malaria infection was estimated using a logistic regression of the fever on a monotonic function of the parasite density and, using bootstrap facilities, bootstrapped estimated confidence intervals, as well as the sensitivity and specificity for different parasite density cut-offs were produced. RESULTS: Overall, the prevalence of Plasmodium falciparum was 52.4% (4,616/8,816). The prevalence of fever (axillary temperature >or= 37.5 degrees C) was 9.4% (766/8,816). Fever episodes peaked among children below 12 months of life [15.1% (206/1,517)]. The lowest fever prevalence of 5.9% (67/1,224) was recorded amongst children between five and seven years of age. Among 4,098 parasitized children, 498/4,098 (13.02%) had fever. The prevalence of malaria infections associated with fever peaked among children in the less than twelve months age group and thereafter decreased rapidly with increasing age (p < 0.001). High parasite densities were significantly associated with fever (p < 0.04). The proportion of fever attributed to malaria was 37.8% (95% CI 32.9% - 42.7%). An age-specific pattern was observed with significant variations across different regions in the country. In general, among children less than 12 months of life, the proportion of fever attributed to malaria infection was 43.5% (95% CI 25.8% - 61.2%), in children aged between 12 and 59 months of age was 39.6% (95% CI 30.3% - 48.9%), and among children aged between 5 and 10 years old was 21.5% (95% CI 11.6% - 31.4%). CONCLUSION: This study confirms that malaria remains a major cause of febrile illness during childhood. It also defines the relation between parasite density and fever and how this varies with age and region. This may help guide case definition for clinical trials of preventive tools, as well as provide definitions that may improve the precision of measurement of the burden of disease.


Assuntos
Sangue/parasitologia , Temperatura Corporal/fisiologia , Febre/etiologia , Malária Falciparum/diagnóstico , Parasitemia/epidemiologia , Plasmodium falciparum/isolamento & purificação , Distribuição por Idade , Animais , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Febre/epidemiologia , Febre/parasitologia , Humanos , Incidência , Lactente , Modelos Logísticos , Malária Falciparum/complicações , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Moçambique/epidemiologia , Parasitemia/parasitologia , Prevalência , Fatores de Risco , Sensibilidade e Especificidade , Fatores Socioeconômicos
10.
J Hypertens ; 24(6): 1057-64, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16685205

RESUMO

OBJECTIVE: To determine whether the response to angiotensin-converting enzyme inhibitor (ACEI) monotherapy in subjects of African origin is determined by genetic variants within the angiotensinogen (AGT) gene. METHODS: A total of 194 hypertensive patients of African ancestry were recruited from district clinics in Johannesburg, South Africa. Eighty patients received open-label ACEI (enalapril or lisinopril) monotherapy, and 114 open-label calcium antagonist (nifedipine) as a drug class comparator. Twenty-four hour ambulatory blood pressure (ABP) monitoring was performed at baseline (off medication) and after 2 months of therapy. DNA was analysed for functional variants (-217G-->A and -20A-->C) of the AGT gene. The impact of genotype on ABP responses to ACEI monotherapy or calcium antagonists; and on plasma aldosterone and renin levels after ACEI monotherapy was assessed. RESULTS: Adjusting for baseline ABP and type of ACEI in the ACEI-treated group, the -217G-->A variant predicted ABP responses to ACEI (n = 77; P < 0.01), but not to nifedipine (n = 108). ACEI in patients with the AA genotype of the -217G-->A variant failed to elicit an antihypertensive response [change in ABP, mmHg: systolic blood pressure (SBP) +0.84 +/- 2.89, P = 0.78; diastolic blood pressure (DBP) -0.47 +/- 1.74, P = 0.79]. In contrast, those patients with at least one copy of the -217G allele developed a 7.23 +/- 1.55 and 5.38 +/- 1.12 mmHg decrease (P < 0.0001) in SBP and DBP, respectively, after ACEI administration. Similarly, the -20A-->C variant predicted ABP responses to ACEI monotherapy (P < 0.01) but not to nifedipine. Moreover, patients who were AA genotype for both variants failed to develop an antihypertensive response to ACEI (change in ABP, mmHg: SBP +1.06 +/- 3.05, P = 0.73; DBP -0.39 +/- 1.83, P = 0.83); whereas patients with at least one copy of both the -217G and the -20C allele developed substantial decreases in ABP (change in ABP, mmHg: SBP -14.08 +/- 3.72, P < 0.0001; DBP -9.62 +/- 2.74, P < 0.0001). Patients with at least one copy of the -217G allele demonstrated a significant reduction in the aldosterone-to-renin ratio (-0.098 +/- 0.035, P < 0.01), whereas in those patients who were -217AA genotype the ratio was unchanged (-0.03 +/- 0.16, P = 0.85). CONCLUSION: Functional variants of the AGT gene contribute to the variability of antihypertensive responses to ACEI monotherapy in individuals of African ancestry, with genotype determining whether or not responses occur.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Angiotensinogênio/genética , População Negra/genética , Pressão Sanguínea/efeitos dos fármacos , Aldosterona/sangue , Índice de Massa Corporal , Bloqueadores dos Canais de Cálcio/farmacologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Renina/sangue , África do Sul
11.
Am J Hypertens ; 16(12): 1006-10, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14643573

RESUMO

BACKGROUND: The severity of hypertension has prognostic significance. Previous studies have assessed the relationship between renin-angiotensin-aldosterone system (RAAS) genotype and the severity of hypertension in either treated patients or those who have only recently discontinued treatment. METHODS: We assessed the impact of RAAS genotype on ambulatory and office blood pressure (BP) in 231 newly diagnosed hypertensive patients of African ancestry who had never received therapy. Subjects were genotyped for variants of the angiotensin-converting enzyme (insertion/deletion), angiotensinogen (M235T, -20A-->C), and aldosterone synthase (CYP11B2)(-344C-->T) genes. RESULTS: The CYP11B2 gene polymorphism was associated with systolic BP (SBP). In comparison to subjects with at least one copy of the -344C allele (n = 75), patients who were homozygous for the -344T allele (n = 156) had both higher ambulatory SBP (150 +/- 1 v 144 +/- 1 mm Hg, P =.002 before and P =.01 after adjusting for multiple genotyping) and office SBP (163 +/- 2 v 156 +/- 2 mm Hg, P =.01 before and P =.05 after adjusting for multiple genotyping). Neither the angiotensin-converting enzyme insertion/deletion nor the angiotensinogen gene polymorphisms were associated with ambulatory or office SBP or diastolic BP (DBP). The CYP11B2 gene variant also did not affect DBP. CONCLUSION: A variant within the CYP11B2 locus has a clinically important impact on the severity of SBP changes in individuals with newly diagnosed hypertension who are of African ethnicity.


Assuntos
População Negra/genética , Citocromo P-450 CYP11B2/genética , Hipertensão/diagnóstico , Hipertensão/genética , Sistema Renina-Angiotensina/genética , Angiotensinogênio/genética , Angiotensinogênio/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Citocromo P-450 CYP11B2/fisiologia , Feminino , Humanos , Hipertensão/etnologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/fisiologia , Sistema Renina-Angiotensina/fisiologia , Índice de Gravidade de Doença , África do Sul
12.
Circulation ; 106(12): 1483-7, 2002 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-12234952

RESUMO

BACKGROUND: The extent to which genes modify the relationship between risk factors for hypertension and blood pressure (BP) is unclear. As angiotensinogen is expressed in adipose tissue and angiotensinogen (AGT) gene promoter variants influence the production of angiotensinogen, we evaluated the role of AGT gene variants as potential modifiers of body size-BP relations. METHODS AND RESULTS: Five hundred twenty-one hypertensives of African origin sampled from a group with a high mean body mass index (BMI) had 24-hour ambulatory BP (ABP) measurements determined off therapy and were genotyped for the AGT -6G-->A, -532C-->T, -20A-->C, and 704T-->C (M235T) gene variants. Genotypes were also determined in 547 control subjects of African origin who had a normal clinic BP. The -6A and -532C alleles were concordant with the M235T variant. Although AGT gene variants had no independent effects on either the presence of hypertension or ABP values in hypertensives, the -20A-->C polymorphism had a marked influence on the relation between ambulatory systolic BP and BMI. This relation was present in patients homozygous for the -20A allele (n=399, r=0.23, P<0.0001), but absent in those with at least one copy of the -20C allele (n=122, r=0.01, P=0.89). The M235T polymorphism did not impact on the BMI-BP relation. Specificity of the -20A-->C polymorphism effect on the BMI-BP relation is further indicated by the lack of effect on the systolic BP-age relation. CONCLUSION: An AGT gene promoter region variant is an important modifier of the relation between body size and BP. Hence, these data corroborate the notion that genetic modifiers can produce a profound impact on BP-phenotypic relations.


Assuntos
Angiotensinogênio/genética , Monitorização Ambulatorial da Pressão Arterial , Hipertensão/diagnóstico , Hipertensão/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Constituição Corporal , Índice de Massa Corporal , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Fenótipo , Fatores de Risco
13.
Cardiovasc J S Afr ; 13(3): 97-101, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12193960

RESUMO

AIM: The roles of the atrial natriuretic peptide (ANP) gene and the clearance receptor of the ANP (NPRC) gene in hypertensive groups of African ancestry are unclear. The aim of the present study was to assess the relationship between both ANP and NPRC gene polymorphisms and hypertension in Black South Africans. METHODS: 298 patients, diagnosed as having essential hypertension according to 24-hour ambulatory blood pressure (BP) measurements (mean daytime diastolic BP> 90 mm Hg) whilst off medication, and 278 normotensive control subjects of a similar African ancestry, were genotyped for polymorphic markers in intron 2 (which is in complete linkage disequilibrium with a potentially functional exon 1 variant) and exon 3 (which leads to the extension of ANP by two additional arginines) of the ANP gene. Moreover, 64 hypertensives and 63 control from the same groups were genotyped for the cis-acting promoter/enhancer element of the NPRC gene. RESULTS: No relationship between the exon 3 variant and either the presence (odds ratio = 1.075) or the severity (24-hour BP) of hypertension was noted. The intron 2 polymorphism occurred at a low frequency in the control group (frequency of subjects heterozygous for the variant = 6.1%), but was almost absent in the hypertensive group (frequency of heterozygotes = 1.7%). Consequently, a relationship between a normal BP and the intron 2 variant was noted (odds ratio = 0.28, confidence interval = 0.10-0.76, p < 0.01, <1% chance of false positive results). The NPRC gene variant occurred with an equally low frequency in both the hypertensive (4.7%) and the control (4.8%) groups. CONCLUSIONS: The results of the present study suggest that the ANP, but not the NPRC locus contributes to BP in subjects of African ancestry.


Assuntos
Fator Natriurético Atrial/genética , População Negra/genética , Pressão Sanguínea/genética , Hipertensão/genética , Polimorfismo Genético , Receptores do Fator Natriurético Atrial/genética , África/etnologia , Feminino , Genótipo , Humanos , Hipertensão/etnologia , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances
14.
Cardiovasc Res ; 54(3): 584-9, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12031704

RESUMO

OBJECTIVE: To assess whether renin-angiotensin-aldosterone (RAA) system gene polymorphisms shown to be associated with alterations in the activity of the system, may predict cardiac function changes subsequent to initiating medical therapy in heart failure. METHODS: The impact of RAA system genotypes on left ventricular ejection fraction (LVEF) following therapy to patients with idiopathic dilated cardiomyopathy (IDC) and class II-III heart failure was assessed. In 107 patients LVEF and LV dimensions were determined using radionuclide ventriculography and echocardiography prior to and subsequent to receiving furosemide, digoxin and angiotensin-converting enzyme (ACE) inhibitor therapy. Patients and controls were genotyped for variants of the ACE (insertion-deletion polymorphism), angiotensinogen (AGT; M235T polymorphism) and the aldosterone synthase (CYP11B2, C-344T polymorphism) genes. RESULTS: RAA system genotypes were not significantly associated with LVEF prior to initiating medical therapy. However, the CYP11B2 gene variant (P=0.0064 on covariate analysis [adjusted for multiple genotyping] with a 1-2% chance of false positive data), but neither the ACE, nor the AGT variants, predicted improvement in LV ejection fraction in patients on medical therapy. CONCLUSION: A CYP11B2 gene variant predicts the variable improvement in LV ejection fraction that occurs subsequent to initiating medical therapy in IDC. These data suggest a role for the aldosterone synthase locus in regulating the progression of heart failure.


Assuntos
Cardiomiopatia Dilatada/enzimologia , Cardiomiopatia Dilatada/fisiopatologia , Citocromo P-450 CYP11B2/genética , Polimorfismo Genético , Volume Sistólico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiotensinogênio/genética , Cardiomiopatia Dilatada/patologia , Estudos de Casos e Controles , Digoxina/uso terapêutico , Diuréticos/uso terapêutico , Ecocardiografia , Inibidores Enzimáticos/uso terapêutico , Feminino , Furosemida/uso terapêutico , Ventrículos do Coração/patologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Ventriculografia com Radionuclídeos
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