Validação de um escore para predição de eventos hemorrágicos em síndromes coronarianas agudas

FUNDAMENTO: Sangramento é uma complicação grave em pacientes tratados para síndromes coronarianas agudas (SCA) com antitrombóticos e terapias invasivas. Consequentemente, o benefício dessas terapias deve ser analisado contra os potenciais riscos de complicações hemorrágicas. Desta forma, a determinação de um escore para estimar o risco individual de sangramento pode representar uma importante ferramenta na tomada de decisões clínicas. OBJETIVO: Criar e validar um escore de risco de sangramento para pacientes com SCA. MÉTODOS: Foram utilizados preditores independentes de sangramento relatados pelo Registro GRACE. Variáveis com odds ratio (OR) > 2,5 nesse Registro somaram 3 pontos (histórico anterior de sangramento), OR=1,5-2,4 somaram 2 pontos (clearance de creatinina< 30 ml/min, sexo feminino) e aquelas com OR < 1,5 somaram 1 ponto (clearance entre 30 e 60 ml/min, a cada 10 anos de idade > 30, infra ou supra-desnivelamento do segmento ST, doença arterial periférica e fumo). O escore foi validado em uma coorte de 383 indivíduos com SCA. Sangramento hospitalar foi definido como queda de hematócrito > 10%, transfusão de sangue > 2 unidades, sangramento intracerebral ou sangramento fatal. RESULTADOS: A incidência de eventos hemorrágicos foi de 3,1% e a estatística-C do escore foi 0,66 (IC95% = 0,52-0,80), indicando capacidade preditiva para esses eventos. Aqueles com escore > 7 apresentaram 6% de incidência de sangramento, comparados com 1,9% se o escore era < 7 (RR=3,2; IC95%=1,04-9,9; p=0,03). Houve uma interação entre um escore > 7 e um maior risco imposto pelo tratamento com Clopidogrel (p=0,02), bloqueadores IIb/IIIa (p=0,06) e revascularização cirúrgica (p < 0,001). CONCLUSÃO: O escore discrimina o risco de sangramento e é potencialmente útil na tomada de decisão clínica em SCA.

Valor preditivo da frequência cardíaca em repouso do teste ergométrico na mortalidade

FUNDAMENTO: A frequência cardíaca em repouso (cuja média está entre 60 e 80 bpm) é uma das mais simples variáveis cardiovasculares e tem sido considerada como um preditor de mortalidade cardiovascular e geral. OBJETIVO: Avaliar o valor preditivo da frequência cardíaca em repouso (FCR), antes do teste ergométrico (TE), na mortalidade cardiovascular (CV) e geral. MÉTODOS: Estudo de caso-controle, que utilizou informações contidas nos bancos de dados do laboratório de ergometria de um hospital especializado em cardiologia e os registros de óbitos da Secretaria da Saúde em uma cidade do sul do Brasil, de janeiro de 1995 a junho de 2007. Foram analisados 7.055 pacientes, sendo 1.645 (23,3%) do grupo caso (óbitos) e 5.410 (76,7%) do grupo controle (vivos). Foi calculado o ponto de corte da FCR para mortalidade, através da curva ROC e realizada a análise multivariada para as variáveis selecionadas. Os desfechos foram mortalidade CV e geral. RESULTADOS: A incidência de mortalidade CV foi de 674 casos (9,5%); a FCR > 78 bpm foi o ponto de corte. Após ajustado para as variáveis selecionadas, o odds ratio (OR) para FCR > 78 bpm foi de 3,5 (IC 95% = 2,9 - 4,2) para mortalidade CV e 3,6 (IC 95% = 3,2 - 4,0) para mortalidade geral. CONCLUSÃO: A FCR > 78 bpm é um preditor independente de mortalidade cardiovascular e geral.

Desfechos clínicos aos 30 dias do registro brasileiro das síndromes coronárias agudas (ACCEPT)

FUNDAMENTO: São escassos os registros documentando a prática clínica brasileira na vigência de uma síndrome coronária aguda. OBJETIVOS: Descrição da demografia, ocorrência de desfechos graves e análise comparativa dentre aqueles que efetivaram ou não uma estratégia invasiva (cinecoronariografia e revascularização miocárdica) em um registro brasileiro multicêntrico de portadores de uma síndrome coronária aguda. MÉTODOS: O registro ACCEPT/SBC coletou prospectivamente, em 47 centros hospitalares brasileiros, pacientes na vigência de uma síndrome coronária aguda. Apresentamos a ocorrência de desfechos clínicos graves, de modo integral, e de acordo com a submissão ou não a um procedimento de revascularização do miocárdio ao final dos primeiros 30 dias de seguimento. RESULTADOS: De agosto de 2010 até dezembro de 2011, 2.485 pacientes foram incluídos neste registro. Destes, 31,6% eram portadores de angina instável e 34,9% e 33,4%, com síndrome sem e com supradesnível do segmento ST. Aos 30 dias, a submissão a procedimento de revascularização do miocárdio foi progressivamente maior de acordo com a gravidade da apresentação clínica (38,7% versus 53,6% versus 77,7%; p < 0,001). A ocorrência de mortalidade cardíaca, dentre aqueles submetidos ou não à revascularização miocárdica, foi de 1,0% versus 2,3% (p = 0,268), 1,9% versus 4,2% (p = 0,070) e 2,0% versus 8,1% (p < 0,001), angina instável, síndrome sem e com supradesnível do segmento ST, respectivamente. CONCLUSÕES: A prescrição de revascularização do miocárdio foi progressivamente mais frequente de acordo com a gravidade da apresentação clínica; naqueles atendidos na vigência de síndrome coronária sem e com supradesnível do segmento ST, promoveu tendência e redução significativa da mortalidade, aos 30 dias, respectivamente.

Diabetes subdiagnosticado e necrose miocárdica: preditores de hiperglicemia no infarto do miocárdio

FUNDAMENTO: Hiperglicemia na fase aguda do infarto do miocárdio é importante fator prognóstico. Entretanto, sua fisiopatologia não está completamente elucidada. OBJETIVO: Analisar simultaneamente correlação entre hiperglicemia e marcadores bioquímicos relacionados ao estresse,metabolismo glicídico e lipídico, coagulação, inflamação e necrose miocárdica. MÉTODOS: Oitenta pacientes com infarto agudo do miocárdio foram incluídos prospectivamente. Os parâmetros analisados foram: glicose, hormônios do estresse (cortisol e norepinefrina), fatores do metabolismo glicídico [hemoglobina glicada (HbA1c), insulina], lipoproteínas (colesterol total, LDL, HDL, LDL eletronegativa minimamente modificada e adiponectina), glicerídeos (triglicérides, VLDL e ácido graxo), fatores da coagulação (fator VII, fibrinogênio,inibidor do ativador do plasminogênio-1), inflamação (proteína C reativa ultrassensível) e necrose miocárdica (CK-MB e troponina). Variáveis contínuas foram convertidas em graus de pertinência por intermédio de lógica fuzzy. RESULTADOS: Houve correlação significativa entre hiperglicemia e metabolismo glicídico (p < 0,001), lipoproteínas (p = 0,03) e fatores de necrose (p = 0,03). Na análise multivariada, somente metabolismo glicídico (OR = 4,3; IC = 2,1-68,9 e p < 0,001) e necrose miocárdica (OR = 22,5; IC = 2-253 e p = 0,012) mantiveram correlação independente e significativa.Para análise da influência da história de diabetes mellitus , modelo de regressão, incluindo somente pacientes sem diabetes mellitus foi desenvolvido, e os resultados não alteraram. Finalmente, no modelo ajustado para idade, sexo e variáveis clínicas(história de diabetes mellitus, hipertensão arterial e dislipidemia), três variáveis mantiveram associação significativa e independente com hiperglicemia: metabolismo glicídico (OR = 24,1; IC = 4,8-122,1 e p < 0,001) necrose miocárdica (OR = 21,9; IC = 1,3-360,9 e p = 0,03) e história de DM (OR = 27, IC = 3,7-195,7 e p = 0,001). CONCLUSÃO: Marcadores do metabolismo glicídico e necrose miocárdica foram os melhores preditores de hiperglicemia em pacientes com infarto agudo do miocárdio.

Determinação de cálcio "trocável" em solos por fotometria e chama

O presente trabalho relata o método de determinação do cálcio "trocável" dos solos do Estado de São Paulo, baseado na fotometria de chama. O método baseado na fotometria de chama foi comparado com o permanganométrico, através da determinação do cálcio "trocável" em 10 amostras de terra, tendo sido feitas 5 repetições com cada método. QUARDO 4 Cálcio «trocável» em solos, determinado pelo método permaíiganométrico e por fotometria de chama (média de 5 repetições). Solo Permanganometria Fotometria de chama n.o e. mg/100 g de solo e.mg/100 g de solo 1 3,58 ± 0,004 3,75 ± 0,040 2 2,60 ± 0,059 2,53 ± 0,026 3 0,54 ± 0,025 0,69 ± 0,034 4 0,39 ± 0,036 0,37 ± 0,020 5 3,61 ± 0,027 3,22 ± 0,044 6 9,41 ± 0,038 9,40 ± 0,074 7 1,00 ± 0,000 0,93 ± 0,001 8 1,79 ± 0,032 1,53 ± 0,069 9 1,00 ± 0,000 0,92 ± 0,000 10 0,60 ± 0,027 0,58 ± 0,033 Foi estudada também a influência de diversos íons (magnésio, manganês, potássio, sódio, ferro, alumínio e fosfato) na determinação do cálcio por fotometria de chama. O método de determinação do cálcio "trocável" do solo, baseado em fotometria de chama forneceu resultados equivalentes ao método permanganométrico, com enorme vantagem na rapidez.

Daily physical activities and sports in adult survivors of childhood cancer and healthy controls: a population-based questionnaire survey.

BACKGROUND: Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. METHODOLOGY/PRINCIPAL FINDINGS: The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976-2003 at age 0-15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5 years and reached adulthood (≥20 years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35 years: 1.5, 95CI 1.2-2.0), female gender (OR 1.6, 95CI 1.3-1.9), French/Italian Speaking (OR 1.4, 95CI 1.1-1.7), and higher education (OR for university education: 2.0, 95CI 1.5-2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1-1.6), older age (OR for ≥35 years: 1.4, 95CI 1.1-1.8), migration background (OR 1.5, 95CI 1.3-1.8), French/Italian speaking (OR 1.4, 95CI 1.2-1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2-2.2), being married (OR 1.7, 95CI 1.5-2.0), having children (OR 1.3, 95CI 1.4-1.9), obesity (OR 2.4, 95CI 1.7-3.3), and smoking (OR 1.7, 95CI 1.5-2.1). Type of diagnosis was only associated with sports. CONCLUSIONS/SIGNIFICANCE: Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population.

Results of computer assisted navigation in Total Knee Arthroplasty (TKA): comparison with the conventional method

The aim of this retrospective study was to compare the clinical and radiographic results after TKA (PFC, DePuy), performed either by computer assisted navigation (CAS, Brainlab, Johnson&Johnson) or by conventional means. Material and methods: Between May and December 2006 we reviewed 36 conventional TKA performed between 2002 and 2003 (group A) and 37 navigated TKA performed between 2005 and 2006 (group B) by the same experienced surgeon. The mean age in group A was 74 years (range 62-90) and 73 (range 58-85) in group B with a similar age distribution. The preoperative mechanical axes in group A ranged from -13° varus to +13° valgus (mean absolute deviation 6.83°, SD 3.86), in group B from -13° to +16° (mean absolute deviation 5.35, SD 4.29). Patients with a previous tibial osteotomy or revision arthroplasty were excluded from the study. Examination was done by an experienced orthopedic resident independent of the surgeon. All patients had pre- and postoperative long standing radiographs. The IKSS and the WOMAC were utilized to determine the clinical outcome. Patient's degree of satisfaction was assessed on a visual analogous scale (VAS). Results: 32 of the 37 navigated TKAs (86,5%) showed a postoperative mechanical axis within the limits of 3 degrees of valgus or varus deviation compared to only 24 (66%) of the 36 standard TKAs. This difference was significant (p = 0.045). The mean absolute deviation from neutral axis was 3.00° (range -5° to +9°, SD: 1.75) in group A in comparison to 1.54° (range -5° to +4°, SD: 1.41) in group B with a highly significant difference (p = 0.000). Furthermore, both groups showed a significant postoperative improvement of their mean IKSS-values (group A: 89 preoperative to 169 postoperative, group B 88 to 176) without a significant difference between the two groups. Neither the WOMAC nor the patient's degree of satisfaction - as assessed by VAS - showed significant differences. Operation time was significantly higher in group B (mean 119.9 min.) than in group A (mean 99.6 min., p <0.000). Conclusion: Our study showed consistent significant improvement of postoperative frontal alignment in TKA by computer assisted navigation (CAS) compared to standard methods, even in the hands of a surgeon well experienced in standard TKA implantation. However, the follow-up time of this study was not long enough to judge differences in clinical outcome. Thus, the relevance of computer navigation for clinical outcome and survival of TKA remains to be proved in long term studies to justify the longer operation time. References 1 Stulberg SD. Clin Orth Rel Res. 2003;(416):177-84. 2 Chauhan SK. JBJS Br. 2004;86(3):372-7. 3 Bäthis H, et al. Orthopäde. 2006;35(10):1056-65.

Metabolic and respiratory effects of infused sodium acetate in healthy human subjects.

The metabolic and respiratory effects of intravenous 0.5 M sodium acetate (at a rate of 2.5 mmol/min during 120 min) were studied in nine normal human subjects. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by open-circuit indirect calorimetry. VO2 increased from 251 +/- 9 to 281 +/- 9 ml/min (P < 0.001), energy expenditure increased from 4.95 +/- 0.17 kJ/min baseline to 5.58 +/- 0.16 kJ/min (P < 0.001), and VCO2 decreased nonsignificantly (211 +/- 7 ml/min vs. 202 +/- 7 ml/min, NS). The extrapulmonary CO2 loss (i.e., bicarbonate generation and excretion) was estimated at 48 +/- 5 ml/min. This observation is consistent with 1 mol of bicarbonate generated from 1 mol of acetate metabolized. Alveolar ventilation decreased from 3.5 +/- 0.2 l/min basal to 3.1 +/- 0.2 l/min (P < 0.001). The minute ventilation (VE) to VO2 ratio decreased from 22.9 +/- 1.3 to 17.6 +/- 0.9 l/l (P < 0.005), arterial PO2 decreased from 93.2 +/- 1.9 to 78.7 +/- 1.6 mmHg (P < 0.0001), arterial PCO2 increased from 39.2 +/- 0.7 to 42.1 +/- 1.1 mmHg (P < 0.0001), pH from 7.40 +/- 0.005 to 7.50 +/- 0.007 (P < 0.005), and arterial bicarbonate concentration from 24.2 +/- 0.7 to 32.9 +/- 1.1 (P < 0.0001). These observations indicate that sodium acetate infusion results in substantial extrapulmonary CO2 loss, which leads to a relative decrease of total and alveolar ventilation.

No healthy heart for heavy drinkers: a population-based study in Switzerland

Background: Low to moderate alcohol consumption has been associated with lower coronary heart disease (CHD) risk, an effect mainly mediated by an increase in HDL-cholesterol levels. However, data on the CHD risk associated with high alcohol consumption are conflicting. Methods: In a population-based study of 5,769 men and women, aged 35-75 years, without cardiovascular disease in Switzerland, last week alcohol consumption was categorized into 0, 1-6, 7-13, 14-20, 21-27, 28-34, 035 drinks/week and into nondrinkers (0 drink/week), moderate (1-13), high (14-34) and very high drinkers (035). Blood pressure, lipids and high sensitivity C-reactive protein (hs-CRP) were measured, and the 10-year CHD risk was calculated according to the Framingham risk score. Results: 73% (n = 4,214) of the participants consumed alcohol; 16% (n = 909) were considered as high drinkers and 2% (n = 119) as very high drinkers. In multivariate analysis, increasing alcohol consumption was associated with higher HDL-cholesterol (from 1.57 ± 0.01 [adjusted mean ± SE] in nondrinkers to 1.88 ± 0.03 mmol/L in very high drinkers); triglycerides (1.17 ± 1.01 to 1.32 ± 1.05 mmol/L), and systolic and diastolic blood pressure rose significantly (127.4 ± 0.4 to 132.2 ± 1.4 and 78.7 ± 0.3 to 81.7 ± 0.9 mm Hg, respectively, all p for trend <0.001). Predicted 10-year CHD risk increased from 4.31 ± 0.10 to 4.90 ± 0.37 (p = 0.03) with increasing alcohol use, with a J-shaped relationship. Conclusion: As measured by the 10-year CHD risk, the protective effect of alcohol consumption disappears in very high drinkers, namely because the beneficial increase in HDL-cholesterol may be blunt by a rise in blood pressure levels.

Low prevalence of abdominal aortic aneurysm in the Seychelles population aged 50 to 65 years.

The prevalence of abdominal aortic aneurysm (AAA) and its risk factors are well known in Western countries but few data are available from low- and middle- income countries. We are not aware of systematically collected population- based data on AAA in the African region. We evaluated the prevalence of AAA in a population- based cardiovascular survey conducted in the Republic of Seychelles in 2004 (Indian Ocean, African region). Among the 353 participants aged 50 to 64 years and screened with ultrasound, the prevalence of AAA was 0.3% (95% CI: 0- 0.9) and the prevalence of ectatic dilatations of the abdominal aorta was 1.5% (95% CI: 0.2- 2.8). The prevalence of AAA in the general population seemed lower in Seychelles than in Western countries, despite a high prevalence in Seychelles of risk factors of AAA, such as smoking (in men), high blood pressure and hypercholesterolaemia.

Acknowledgment and psychiatric symptoms in police officers in Switzerland

The way supervisors acknowledge specific contribution and efforts of their employees has an impact on occupational health and wellbeing. Acknowledgement is a protective factor when it is sufficiently provided. We carried out a study about occupational health in police officers with special emphasis on acknowledgment and reward. A questionnaire was sent to 1000 police officers and inspectors working for a cantonal administration in Switzerland. In total, 695 participants answered the questionnaire. We used the TST questionnaire (French version of the Langner's questionnaire on psychiatric symptoms) to identify cases characterized by potential mental health problems. Multiple choice items (5 modalities ranging from "not at all" to "tremendously") were used to measure acknowledgment. The score for psychiatric symptoms was high (TST score >or= 9) for 86 police officers and inspectors for whom health might be at risk. Compared with police officers having low or medium scores for psychiatric symptoms (TST score < 9), police officers with high TST scores were more likely to report the lack of support and attention from the supervisors (odds ratio [OR] 3.2, 95% confidence interval [CI] 2.0 to 5.1) and the lack of acknowledgment by the hierarchy (OR 3.0, 95% CI 1.9 to 4.8). They were also more likely to mention that judicial authorities have a low consideration for police officers (OR 2.7, 95% CI 1.7 to 4.3) and that the public in general have a low appreciation of police officers (OR 1.8, 95% CI 1.2 to 2.9). Preserving mental health in occupations characterized by high emotional demand is challenging. Our results show that acknowledgment and mental health are associated. Further research should address a potential causal relation of acknowledgment on mental health in police officers and inspectors.

Helical tomotherapy or intensity-modulated radiation therapy in the treatment of anal cancer: experience of Geneva and Lausanne

Background: To assess the early clinical outcomes and toxicities in patients treated with high precision radiation therapy (RT) consisting of helical tomotherapy (HT) or intensity-modulated radiation therapy (IMRT) for anal cancer. Materials and Methods: Since March 2006, 30 patients with stage I-IIIB anal squamous-cell carcinoma were treated curatively by IMRT or HT alone (n = 2) or by concomitant chemotherapy and IMRT or HT (n = 28). Median age was 59 years (range, 36−83 years) and the female/male ratio was 2.3 (21/9). Primary tumor site was anal canal, anal margin, or both in 26, 1, and 3 patients, respectively. Anal tumor, pelvic and inguinal nodes were irradiated with a median dose of 36 Gy using HT, or 5- or 7-field IMRT in 18 and 12 patients, respectively; After a planned gap of 1−2 weeks (median 1 week), a median boost dose of 23.4 Gwas delivered to the tumor and/or involved nodes using 3DRT (n = 24) or HT/IMRT (n = 6). The total delivered dose ranged between 59.4 and 64.8 Gy (median, 59.4 Gy). Concomitant chemotherapy consisted of mitomycin C alone (n = 1), mitomycin C and 5-fluorouracil (n = 17) or capecitabin (n = 10) in 28 patients. Common Terminology Criteria for Adverse Events v3.0 scale was used to score acute and late toxicities. Results: All but one patient, who developed progressive local and distant disease at the end of RT, achieved a complete response. Twelve months following RT, one patient had a recurrence at the primary tumor site, salvaged with brachytherapy. After a median follow-up of 7.5 months (range, 1−35 months), no deaths were observed. The 2-year actuarial locoregional control and probability of disease control without colostomy rates were 82% and 79%, respectively. RT was well tolerated without any unplanned treatment interruptions. Grade 1 or 2 acute adverse events consisted of skin toxicity in 8 and 22 patients, diarrhea in 18 and 3 patients, and cystitis in 9 and 2 patients; respectively. Only one patient developed grade 3 mucosal necrosis at the end of the treatment, requiring diverting colostomy. No difference in terms of acute toxicity was observed between patients treated with HT or IMRT. None of the 22 patients with a follow-up of more than 3 months developed grade 3 or more late toxicity. Conclusions: Our preliminary results suggest that HT or IMRT combined with concomitant chemotherapy for anal cancer is effective, and associated with favorable rates of toxicity compared with historical series. Further follow-up is warranted to assess late toxicity.

Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption.

Moderate alcohol consumption has been associated with lower coronary artery disease (CAD) risk. However, data on the CAD risk associated with high alcohol consumption are conflicting. The aim of this study was to examine the impact of heavier drinking on 10-year CAD risk in a population with high mean alcohol consumption. In a population-based study of 5,769 adults (aged 35 to 75 years) without cardiovascular disease in Switzerland, 1-week alcohol consumption was categorized as 0, 1 to 6, 7 to 13, 14 to 20, 21 to 27, 28 to 34, and > or =35 drinks/week or as nondrinkers (0 drinks/week), moderate (1 to 13 drinks/week), high (14 to 34 drinks/week), and very high (> or =35 drinks/week). Blood pressure and lipids were measured, and 10-year CAD risk was calculated according to the Framingham risk score. Seventy-three percent (n = 4,214) of the participants consumed alcohol; 16% (n = 909) were high drinkers and 2% (n = 119) very high drinkers. In multivariate analysis, increasing alcohol consumption was associated with higher high-density lipoprotein cholesterol (from a mean +/- SE of 1.57 +/- 0.01 mmol/L in nondrinkers to 1.88 +/- 0.03 mmol/L in very high drinkers); triglycerides (1.17 +/- 1.01 to 1.32 +/- 1.05 mmol/L), and systolic and diastolic blood pressure (127.4 +/- 0.4 to 132.2 +/- 1.4 mm Hg and 78.7 +/- 0.3 to 81.7 +/- 0.9 mm Hg, respectively) (all p values for trend <0.001). Ten-year CAD risk increased from 4.31 +/- 0.10% to 4.90 +/- 0.37% (p = 0.03) with alcohol use, with a J-shaped relation. Increasing wine consumption was more related to high-density lipoprotein cholesterol levels, whereas beer and spirits were related to increased triglyceride levels. In conclusion, as measured by 10-year CAD risk, the protective effect of alcohol consumption disappears in very high drinkers, because the beneficial increase in high-density lipoprotein cholesterol is offset by the increases in blood pressure levels.

JNK inhibition and inflammation after cerebral ischemia.

The c-Jun-N-terminal kinase signaling pathway (JNK) is highly activated during ischemia and plays an important role in apoptosis and inflammation. We have previously demonstrated that D-JNKI1, a specific JNK inhibitor, is strongly neuroprotective in animal models of stroke. We presently evaluated if D-JNKI1 modulates post-ischemic inflammation such as the activation and accumulation of microglial cells. Outbred CD1 mice were subjected to 45 min middle cerebral artery occlusion (MCAo). D-JNKI1 (0.1 mg/kg) or vehicle (saline) was administered intravenously 3 h after MCAo onset. Lesion size at 48 h was significantly reduced, from 28.2+/-8.5 mm(3) (n=7) to 13.9+/-6.2 mm(3) in the treated group (n=6). Activation of the JNK pathway (phosphorylation of c-Jun) was observed in neurons as well as in Isolectin B4 positive microglia. We quantified activated microglia (CD11b) by measuring the average intensity of CD11b labelling (infra-red emission) within the ischemic tissue. No significant difference was found between groups. Cerebral ischemia was modelled in vitro by subjecting rat organotypic hippocampal slice cultures to oxygen (5%) and glucose deprivation for 30 min. In vitro, D-JNKI1 was found predominantly in NeuN positive neurons of the CA1 region and in few Isolectin B4 positive microglia. Furthermore, 48 h after OGD, microglia were activated whereas resting microglia were found in controls and in D-JNKI1-treated slices. Our study shows that D-JNKI1 reduces the infarct volume 48 h after transient MCAo and does not act on the activation and accumulation of microglia at this time point. In contrast, in vitro data show an indirect effect of D-JNKI1 on the modulation of microglial activation.

Resistance of Plamodium falciparum to Antimalarial Drugs in Zaragoza (Antioquia, Colombia), 1998

Plasmodium falciparum sensitivity to chloroquine (CHL), amodiaquine (AMO) and sulfadoxine/pyrimethamine (SDX/PYR) was assessed in vivo and in vitro in a representative sample from the population of Zaragoza in El Bajo Cauca region (Antioquia-Colombia). There were 94 patients with P. falciparum evaluated. For the in vivo test the patients were followed by clinical examination and microscopy, during 7 days. The in vitro test was performed following the recommendations of the World Health Organization. The in vivo prevalence of resistance to CHL was 67%, to AMO 3% and to SDX/PYR 9%. The in vitro test showed sensitivity to all antimalarials evaluated. Concordance for CHL between the in vivo and in vitro tests was 33%. For AMO and SDX/PYR, the concordance was 100%. We conclude that a high percentage of patients are resistant to CHL (in vivo). A high rate of intestinal parasitism might explain in part, the differences observed between the in vivo and the in vitro results. Therefore, new policies and treatment regimens should be proposed for the treatment of the infection in the region. Nationwide studies assessing the degree of resistance are needed.