Associations between OPG and RANKL polymorphisms, vertebral fractures, and abdominal aortic calcification in community-dwelling older subjects: the Sao Paulo Ageing & Health Study (SPAH).

This is the first study analyzing concomitantly osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) polymorphisms and OPG/RANKL serum levels and their association with bone mineral density (BMD), vertebral fractures, and vascular aortic calcification in a cohort of 800 subjects in community-dwelling older individuals. INTRODUCTION: Osteoprotegerin (OPG) and RANKL play an important role in osteoclast activation and differentiation as well as in vascular calcification. At present, there are no studies of OPG or RANKL gene polymorphisms in Brazilian older populations. The aim of this study was to evaluate OPG/RANKL polymorphism and their association with vertebral fractures (VFs) and aortic calcification. METHODS: Eight hundred subjects (497 women/303 men) were genotyped for the OPG 1181G>C (rs2073618), 163C>T (rs3102735), 245T>G (rs3134069), and 209G>A (rs3134070) and RANKL A>G (rs2277438) single-nucleotide polymorphisms (SNPs). VFs were evaluated by spine radiography (Genant's method). Aortic calcification was quantified using Kauppila's method. RESULTS: The isolated genotype analyses and single-allele frequency data showed association of OPG 163C, 245G, and 209A alleles with presence of VFs (P < 0.05). Multiple logistic regression of subjects with absence of VFs vs. those with VFs (grades II/III) revealed only OPG 209A homozygosity as a risk factor for higher-grade VFs (odds ratio (OR) = 4.17, 95 % CI 1.03-16.93, P = 0.046). Regarding aortic calcification, the isolated genotype analysis frequency data revealed a significant association of OPG 1181G, 163C, 245G, and 209A alleles with absent aortic calcification (P < 0.05). Multiple logistic regression data confirmed that the OPG 209A allele was protective for aortic calcification (OR = 0.63, 95 % CI 0.45-0.88, P = 0.007) and the OPG 1181C allele was a risk factor for aortic calcification (OR = 1.26, 95 % CI 1.00-1.58, P = 0.046). CONCLUSION: This study showed that the OPG 209AA genotype was a risk factor for higher-grade VFs, the OPG 209A allele was protective for aortic calcification, and the OPG 1181C was a risk factor for aortic calcification, supporting the involvement of OPG polymorphisms in the analyzed phenotypes and the concept that the related pathogenesis is multifactorial.

A clonal Plasmodium falciparum population in an isolated outbreak of malaria in the Republic of Cabo Verde.

We present the first parasitological, molecular and longitudinal analysis of an isolated outbreak of malaria. This outbreak occurred on Santiago Island (Republic of Cabo Verde), a region where malaria is hypoendemic and controlled, and thus the population is considered non-immune. Blood samples were collected from the inhabitants over 1 month and during cross-sectional surveys in the following year. The presence and nature of the parasites was determined by PCR. Plasmodium falciparum was the only species detected. Genetic analysis revealed that the circulating parasites were genetically homogeneous, and probably clonal. Gametocytes were found throughout this period. Our data suggest that this represented a focal outbreak, resulting in the infection of at least 40% of the villagers with a clonal parasite line. Thus, P. falciparum infections can persist for at least 1 year in a substantial proportion (10%) of the hosts. Implications for malaria control and the interpretation of epidemiological data are discussed.

Can a clinical classification of stroke predict complications and treatments during hospitalization?

The predictive value of the Oxfordshire Community Stroke Project ischemic stroke classification for acute stroke complications, therapeutic interventions and disability at discharge was investigated in 297 consecutive first-ever acute stroke patients. More than one medical complication (odds ratio, OR = 2.2), fever (OR = 2.5) and dependency (Rankin grade > 2) at discharge (OR = 2.3) were more frequent in intracerebral hemorrhage patients. Fever and urinary tract infections were the most common complications among ischemic stroke patients. Both were more frequent in total anterior circulation infarct (TACI) patients (OR = 11.5 and OR = 3.7). Neurological deterioration was observed in about 10% of TACI and posterior circulation infarct (POCI) patients. Dependency at discharge was more frequent in TACI patients (OR = 10.3). Logistic regression analysis identified ischemic stroke subgroups (OR = 8.4) and medical complications (OR = 3.8) as predictors of poor outcome (Rankin score > or = 4). A clinical classification is useful to predict possible medical and neurological complications in the acute phase, death and dependency at discharge.

Transmission of mixed malaria species and strains by mosquitoes, as detected by PCR, in a study area in Guinea-Bissau.

Parasites present in blood samples of asymptomatic carriers and in the midgut of mosquitoes collected within a few days from the same households, have been analysed by PCR. A high prevalence (32%) of infected mosquitoes was observed and, in half of these, two parasite species were found simultaneously. The distribution of parasite species in the mosquito correlated with that found in the infected persons. Genotype patterns of Plasmodium falciparum populations were however found to be different in the two sets of samples. These results and the potential of PCR are discussed with reference to investigations of the dynamics of malaria transmission.

[Acute cerebrovascular disorder and arterial hypertension. Prospective study with 248 patients]. / O acidente vascular cerebral agudo e a hipertensão arterial. Estudo prospectivo com 248 doentes.

OBJECTIVE: To evaluate the hypertension associated to different types and sub-types of cerebrovascular disease (stroke), with particular reference to the frequency of hypertension, the values of blood pressure, the risk factors and the involvement of other target organs. DEFINITION: Prospective study in 248 patients with acute stroke admitted to a Clinical Medicine Unit in three independent time periods. SETTING: Internal Medicine Clinic of University Hospital in Lisbon. METHODS: Medical, neurological and cardiologic examination were performed and all patients were also submitted to different complementary tests, including a computer tomography scan of the brain, and an echocardiogram. The values of blood pressure were measured in the admission at the urgent service and 24 h after in the the ward. We identified three sub-types of stroke: intracerebral hemorrhage (IH), ischaemic stroke (IS) and lacunes (L). For each sub-type and for those with hypertension or not, we evaluated: age, sex, duration of stay in hospital and mortality. We also compared for each sub-type the values of blood pressure, the risk factor and the repercussion on other target organs. PATIENTS: Two hundred and forty eight patients (52% were men) with mean age 68.0 +/- 10.2 years, and ages among 40 and 92 years. Thirty-seven patients (15%) died. MAIN RESULTS: In the entire population (n = 248) hypertension were more prevalent in IH 83% and L 82% than in IS 59% (p < 0.0005). Hypertension was present in 172 patients (69%) and 81 (47%) were IS, 58 (34%) L and 33 (19%) IH. Sixty six percent of the 172 patients with hypertension had at least another risk factor and the most aged ones (> 65 years old) were more frequent in IS 75% than in HI 45% or L 58% (p < 0.001). For all subtypes blood pressure measurements were higher in admission than in ward and they were also higher in IH than in IS (p < 0.05). Hypertensive cardiopathy was more prevalent in IH 76% and L 61% than in IS 49% (p < 0.05). Renal failure was more frequent in IS 37% than in IH 28% and L 17% (p < 0.05). CONCLUSIONS: Hypertension is very frequent, and like advanced age is a major risk factor of stroke. Hypertension is frequently associated with one or more risk factors. Hypertensive cardiopathy is more related with IH and L and the renal involvement with IS.

[Pneumonia in an internal medicine service]. / Pneumonias num serviço de medicina interna.

A retrospective study was performed in 107 patients with pneumonia in a total of 2231 who were admitted in a Medicine ward, of an University Hospital in Lisbon during 1990. From the studied patients, 50 (46,7%) were females and 57 (53,3%) males. The mean age was 70,7 +/- 15,3 years, with a mean of 12.8 admission days. In the past history it was identified 43 (40%) patients with respiratory illness. In this, the chronic obstructive airways disease were the more prevalent disease in 22 (20.5%) patients. In the other chronic debilitating diseases, registered in 90 (84.1%), we reported in 58 (54.2%) patients among cardiovascular illness, hypertension (H) in 17 (15.8%) cases and H with diabetes mellitus II (DMII) in 14 (13.1%). The most common radiographic pattern was bronchopneumonia in 56 (52.3%) cases and in the respiratory functional study, the partial respiratory insufficiency occurred in 25 (23.4%) cases. In blood test at admission, it was found anaemia in 35 (32.7%) patients, leukocytosis in 72 (67.3%), elevated sedimentation rate in 70 (65.4%), renal dysfunction in 12 (11.2%) and hyperglycemia in 67 (62.6%). Concerning therapeutics, the ampicillin was the most used antimicrobial therapy in 50 (46.7%) cases and the oxygenotherapy was necessary in 45 (42%). Only 29 (27.1%) needed bronchodilators and 3 (2.8%) required mechanical ventilatory support. The evolution was good in 76 (71%) cases and 31 (29%) patients died. The authors conclude that the pneumonia is a frequent disease in the Internal Medicine Clinics, either as admission cause either as complication of other comorbid medical condition and has a high mortality rate. The most important factors for the prognosis were the age of patients and previous diseases. The aim of the authors is to enhance prevention infection in lower respiratory tract, principally in the weak constitutions patients and the prescription of the appropriate therapy according with the judgment presumption and if possible with the isolated microorganism. Identify with the retrospective study, important elements in the clinical process for interpretation of diagnosis and therapeutic attitude and to learn with the preceding experience for future orientation.

[Acute cerebrovascular accident and heart disease. Prospective study of 248 patients]. / O acidente vascular cerebral agudo e a doença cardíaca. Estudo prospectivo com 248 doentes.

OBJECTIVE: To evaluate the heart disease associated to different type and sub-types of cerebrovascular disease with particular reference to potential cardiac sources of embolus (CPE). DESIGN: Prospective study in 248 consecutive patients with acute stroke, admitted to a Clinical Medicine Unit in three independent time periods. SETTING: Internal Medicine Clinic of University Hospital in Lisbon. METHODS: Neurologic and cardiologic examination were performed and all patients were also submitted to different complementary tests, including a Computer Tomography Scan of the brain (TAC) and a Echocardiogram (ECO). We identified two types and two sub-types: intracerebral haemorrhage (HI) or ischemic stroke (AI) and among AI, cortical (C) or subcortical (SC) ischemic stroke. For each type and sub-type we evaluated past history, heart disease, hypertension (HTA), electrocardiogram, echocardiogram (ECO) and CPE. PATIENTS: Two hundred and forty eight patients (52% were men) with mean age 68.0 +/- 10.2 years and ages between 40 and 92 years. Thirty seven (15%) died. MAIN RESULTS: Eighty four percent were AI and among them 45% were C. Previous strokes were more prevalent in AI 29% (p < 0.01). There was heart disease in 81% and hypertensive cardiopathy was more frequent in HI 63% (p < 0.002). HTA and atrial fibrillation (FA) were more frequent in HI 83% (p < 0.05) and in AI 25% (p < 0.004) respectively. ECO showed a dilatation of left atrium more frequent in AI 28% (p < 0.05) and left ventricular concentric hypertrophy index (IHCE) in HI 50% (p < 0.05). CPE, including FA, was identified in 34% of patients, was more prevalent in AI 38% (p < 0.001) and among it FA was significantly more frequent in C 32% (p < 0.02). CONCLUSIONS: Heart disease is very frequent in stroke. The diagnosis of this condition is very important for stroke prophylaxis and prognosis. HTA and hypertensive cardiopathy have a great prevalence and were more related to HI. CPE and FA were very frequent and their diagnosis are important for prevention of AI and specially for embolic stroke. ECO is useful to identify CPE in elderly patient in particular to characterize heart disease.

[Assessment of arterial occlusive disease with Duplex sonography. Prospective study]. / Avaliação da doença oclusiva das artérias renais com Triplex Scan. Estudo prospectivo.

Occlusive disease involving the renal arteries represent a major cause of curable hypertension and improvement of renal dysfunction. Angiography is still the major diagnostic procedure. Isotopic methods with Captopril and split-function studies have shown high incidence of false-positive and false-negative results. Colour flow Duplex-Scan renders possible the visualization of the aorta and renal arteries, is noninvasive and combines morphologic and hemodynamic evaluation. To assess its efficacy in the diagnosis of renal artery occlusive disease, a prospective blind study was undertaken in 24 patients, 48 renal arteries, 15 women and 9 men, with mean age of 44 years. Scans of the aorta and renal arteries at the origin, along its extension and at the renal hilum were obtained using and ATL Ultrmark 9 with 3.0 MHZ probe Velocity measurements were obtained at the aorta and along the renal arteries. Criteria for a positive examination were: focal acceleration with a reduction of the flow velocity at the hilum. Absence of flow in a properly visualized renal artery was considered as occlusion. All patients had digital subtraction arteriography. In 1 patient the non-invasive examination was inadequate. In the remain 23 patients the exam was considered adequate. False-positives were 4.8%; false-negatives 8.7%. Sensitivity, specificity and accuracy were respectively 91.7%, and 95.7% and 93.5%. These results suggest that non-invasive assessment of renal artery occlusive disease is feasible and accurate when compared to angiography, thus providing a useful tool for screening hypertensive patients.

[The patient with acute cerebrovascular disorders: assessment of associated diseases]. / O doente com acidente vascular cerebral agudo: avaliação da patologia associada.

We performed a prospective study in 106 patients with acute stroke. The main purpose was to evaluate the associated diseases and to determine their prevalence and incidence in two different types of cerebrovascular disease: the intracerebral hemorrhage (HI) and ischaemic events (AI). The studied population included 54 men and 52 women with a mean age of 66.8 +/- 10.3 years. A clinical examination was performed in all patients by different specialists and all were submitted to diverse complementary tests, including a computed tomography scan of the brain (TAC) and an echocardiogram (ECO). We found 24 (23%) HI and 82 (77%) AI. In the past history, previous stroke were more prevalent in AI (p less than 0.01). Heart disease was present in 87 (82%) patients but, among them, only atrial fibrillation which was found in 19 (18%) patients, was significantly more frequent in AI (p less than 0.02). Hypertension (HTA) existed in 79 (75%) patients, respiratory complications and periferic vascular disease in 9 (8%), diabetes in 44 (42%) and dyslipidemia in 31 (29%) patients. No significant difference was found between the two groups of stroke regarding these diseases; however, there was a tendency for HTA and diabetes to be more prevalent in HI and for periferic vascular disease in AI. In the blood tests, high haematocrit was found in 35 (33%) patients, anemia in 21 (20%), hypercholesterolemia in 17 (16%), hypertrigliceridemia in 18 (17%) and uremia or creatinemia or ionic alteration in 32 (30%) patients, without any difference in their prevalence and incidence in the two groups of stroke. In conclusion, in this prospective study of patients with an acute stroke, there was 23% of HI and 77% of AI, a high prevalence of previous stroke, heart disease and HTA, but only the previous stroke and, within heart disease, the atrial fibrillation were significantly more frequent in the AI group. Also, periferic vascular disease had a tendency to be more frequent in AI, as well as diabetes and HTA had in HI.

[Cerebral vascular disorders and arterial hypertension: cardiologic and neurologic aspects]. / Acidente vascular cerebral e hipertensão arterial: aspectos cardiológicos e neurológicos.

OBJECTIVE: To report and discuss some cardiologic, neurologic and radiologic aspects in different types of stroke (AVC) present in hypertensive patients. DESIGN: Retrospective study in patients with acute cerebrovascular accident (AVC) and high blood pressure (HTA). Separate this population in three groups according to the results of computerized tomography scanning of the brain (TAC): hemorrhage (H) cerebral infarction (IC) and lacune (L). In each group describe the findings. SETTING: Department of Internal Medicine in a University Hospital of Lisbon. PATIENTS: Thirty-four patients, after having discarded 8 because their TAC were normal. Twenty were men (M), 14 women (F) with a total age average of 58 years. MEASUREMENTS AND MAIN RESULTS: All patients had AVC, HTA and underwent initial TAC. For each group were considered: Past history, cardiac repercussions of HTA, neurologic features and the localisations of cerebral lesions. For statistical study were used the Student T Test. There was 45% of IC, 24% of H and 26% of L. In past history was found 35% of cardiac diseases and 24% of diabetes. There wasn't any difference in blood pressure (systolic and diastolic) between the groups. Fifty-six percent had an important cardiac repercussion, with 72% of alterations of ventricular repolarization and 35% of coronary heart diseases. Both were more prevalent in IC than in the others. Twenty percent of H were in physical activity, 20% had a progressive start and in 10% there were meningeal signals. The site of cerebral lesions were characteristical, specially the H and L and 60% of H were thalamic. There wasn't any lacune neither in the cerebral stem nor in the cerebellum. It was reviewed some theoric aspects of neurologic feature. CONCLUSIONS: IC is the more frequent AVC in hypertensive patients. The cardiac involvement, is the most frequent disease in past history. The cardiac repercussion of HTA is more important in IC. The findings were insufficient to well characterize the neurologic feature. Sometime TAC and seldom magnetic resonance are necessary. The localisations, specially of H and L are the same that have been described in medical literature.