We measured circulating endothelial precursor cells (EPCs), activated circulating endothelial cells (aCECs), and mature circulating endothelial cells (mCECs) using four-color multiparametric flow cytometry in the peripheral blood of 84 chronic myeloid leukemia (CML) patients and 65 healthy controls; and vascular endothelial growth factor (VEGF) by quantitative real-time PCR in 50 CML patients and 32 healthy controls. Because of an increase in mCECs, the median percentage of CECs in CML blast crisis (0.0146%) was significantly higher than in healthy subjects (0.0059%, P<0.01) and in the accelerated phase (0.0059%, P=0.01). There were no significant differences in the percentages of CECs in chronic- or active-phase patients and healthy subjects (P>0.05). In addition, VEGF gene expression was significantly higher in all phases of CML: 0.245 in blast crisis, 0.320 in the active phase, and 0.330 in chronic phase patients than it was in healthy subjects (0.145). In conclusion, CML in blast crisis had increased levels of CECs and VEGF gene expression, which may serve as markers of disease progression and may become targets for the management of CML.

In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

Patients with diffuse large B-cell lymphoma treated in a University Hospital were studied from 1990 to 2001. Two treatment regimens were used: ProMACE-CytaBOM and then, from November 1996 on, the CHOP regimen. Complete remission (CR), disease-free survival (DFS), and overall survival (OS) rates were determined. Primary refractory patients and relapsed patients were also assessed. A total of 111 patients under 60 years of age were assessed and ranked according to the international prognostic index adjusted to age. Twenty (18%) of them were classified as low risk, 40 (36%) as intermediate risk, 33 (29.7%) as high intermediate risk, and 18 (16.3%) as high risk. Over a five-year period, OS and DFS rates were 71 and 59%, respectively, for all patients. For the same time period, OS and DFS rates were 72.8 and 61.3%, respectively, for 77 patients treated with CHOP chemotherapy and 71.3 and 60% for patients treated with the ProMACE-CytaBOM protocol. There was no significant difference in OS or DFS between the two groups. Eleven of 50 refractory and relapsed patients were consolidated with high doses of chemotherapy. Three received allogenic and 8 autologous bone marrow transplantation. For the latter, CR was 62.5% and mean OS was 41.1 months. The clinical behavior, CR, DFS, and OS of the present patients were similar to those reported in the literature. We conclude that both the CHOP and ProMACE-CytaBOM protocols can be used to treat diffuse large B-cell lymphoma patients, although the CHOP protocol is preferable because of its lower cost and lower toxicity.

Acute myelogenous leukemia (AML) blast cells show high-affinity degradation of low-density lipoprotein (LDL), suggesting an increased expression of cellular LDL receptors. LDE is a lipid microemulsion easily synthesized in vitro which is known to mimic the metabolic pathway of LDL. We used LDE as a carrier for daunorubicin and assayed the cytotoxicity of the complex using AML blast cells since RT-PCR analysis showed that AML cells express LDL receptor mRNA. The LDE:daunorubicin complex killed 46.7% of blast cells and 20.2% of normal bone marrow cells (P<0.001; Student t-test). Moreover, this complex destroyed AML blast cells as efficiently as free daunorubicin. Thus, LDE might be a suitable carrier of chemotherapeutic agents targeting these drugs to neoplastic cells and protecting normal tissues.

OBJETIVO: Comparar o consumo de hemocomponentes entre recém-nascidos (RN) de termo (RNT) e pré-termo (RNPT) e correlacionar esse consumo ao tipo de tratamento dispensado à sua patologia: clínico ou cirúrgico; acidentes hemorrágicos e sobrevida. CASUÍSTICA E METODOLOGIA: 48 RNs classificados em dois grupos: 26 RNT e 22 RNPT receberam 251 unidades de hemocomponentes: 177 unidades de concentrado de hemácias (CH), 36 de concentrado de plaquetas (CP), 30 de plasma fresco congelado (PFC) e oito de sangue total (ST), no período de 186 dias. Foi analisado o consumo de hemocomponentes em cada grupo, e na razão do número de RNs vivos por dia, até o 120º dia. RESULTADOS: O consumo médio de hemocomponentes foi de 7,31 unidades para RNPT e 3,46 para RNT. A análise de consumo diário revelou que a maior parte ocorreu em RNs sob tratamento clínico antes do 60º dia de vida (d.v.) e que um aumento após o 86º d.v. pode ser atribuído a um aumento de cirurgias nessa fase. Os acidentes hemorrágicos predominaram em RNPT com plaquetometria inferior a 60.000/mm³. Foi constatada uma tendência inversamente proporcional entre o número de transfusões e a sobrevida. CONCLUSÕES: Os RNPT consumiram mais hemocomponentes que os RNT. Esse consumo estava ligado à patologia de base. Foi sugerido que a transfusão profilática de CP em RNPT poderia reduzir o número de hemorragias, além do consumo de CH nesse grupo. Mais de dez transfusões de hemocomponentes nos primeiros 120 d.v., em ambos os grupos, parece constituir marcador de mau prognóstico.

BACKGROUND: Blood transfusion requirements for preterm infants are greater than for newborn ones. We compare blood transfusion requirements for newborn and premature infants and their pathology: clinical or surgical; hemorragic accidents and survival. METHODS: 48 newborns classified in 2 groups: 26 newborn and 22 preterm infants received 251 units of blood components: 177 units of red cell concentrates, 36 of platelet concentrates, 30 of fresh frozen plasma and 8 of total blood in a 186 days period. We analyzed total requirements of components in each group and daily, under a live-infant/day rate until 120 days. RESULTS: The all-components median requirements were 7.31 units for premature and 3.46 for newborn infants. Daily requirements analyzes reveal that requirements were greater before 60th day of life (d.l.) on clinical patients and after 86th d.l. may be caused by surgical acts. Hemorragic accidents happen on premature with less than 60.000 platelets/mm³. The survival wave by number of transfusions, until 186 d.l., shows an inversely proportional trend between the number of transfusions done and the hope of life. CONCLUSIONS: Blood requirements for preterm infants are greater than for term ones. Those requirements are related to their pathology. Prophylatic platelet transfusions may reduce hemorrhagic accidents then red blood cell transfusions in preterm infants group. The number of transfusions over 10 is a surrogate marker of bad prognosis for both groups up to 120 d.l.

Aluminum (Al3+) intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al3+-induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL) of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 &micro;M) stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA) (100 &micro;M) and n-propyl gallate (NPG) (100 &micro;M), inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA) (100 &micro;M), an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation

Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3 females and 7 males aged 65 ± 11 years, 74 ± 16 kg body weight, 166 ± 9 cm height and 1.80 ± 0.21 m2 body surface area (BSA), and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ± 14 years, 66 ± 14 kg body weight, 159 ± 9 cm height and 1.65 ± 0.16 m2 BSA (mean ± SD). Sodium diclofenac (1 mg/kg, im Voltaren 75® twice a day) was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale (VAS) during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMAX) were: 25% VAS (CPB) vs 10% VAS (control), P<0.05, median measured by the visual analogue scale where 100% is equivalent to the highest level of pain. To correlate the effect versus plasma diclofenac levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX) was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinically relevant kinetic-dynamic consequences

A detecção do DNA do Vírus da Hepatite B pela Reação em Cadeia da Polimerase (PCR) foi comparada com os outros marcadores sorológicos virais (AgHBs, AgHBe e anti-HBe) numa série de 49 pacientes com hepatite crônica B, incluindo 12 que apresentaram clareamento espontâneo do AgHBs. Nenhum caso AgHBs negativo foi PCR positivo, mas 33/37 (89,2%) dos casos AgHBs positivos foram PCR positivos (p < 0,0001). Entre as amostras AgHBs positivas, 9 foram AgHBc positivas e anti-HBe negativas, todas elas PCR positivas. Outros 3 pacientes foram AgHBe e anti-HBe positivos, todos também PCR positivos. Um terceiro grupo incluía 21 pacientes anti-HBe positivos e anti-HBe negativos: 19 foram PCR positivos e 2 PCR negativos. Os últimos 4 casos foram AgHBe e anti-HBe negativos, sendo 2 destes PCR positivos. A detecção de casos virêmicos anti-HBe positivos sugere que as variantes preC do VHB podem também estar presentes em nosso país. Em conclusão, a "fase de integração viral" da hepatite crônica B parece ser muito menos frequente do que se imaginava previamente, quando apenas se dispunha das técnicas de detecção de AgHBe e DNA por hibridização. O novo termo "fase de baixa replicação baixa" parece ser melhor que o anterior "fase de integração viral" .

Detection of HBV-DNA by PCR was compared with other serological markers (HBsAg, HBeAg and anti-HBe) in a series of49 Chronic Hepatitis B patients, including 12 with a spontaneous clearance of HBsAg. None of these HBsAg negative cases were PCR positive, but 33/37 (89.2%) HBsAg positive cases were PCR positive (p < 0.0001). Among HBsAg positive samples, nine cases were HBeAg positive and anti-HBe negative, all of them PCR positive. Other 3 patients were HBeAg and anti-HBe positive and these cases were also found PCR positive. A third group included 21 patients anti-HBe positive and HBeAg negative: 19 of them were PCR positive and 2 were PCR negative. The last 4 cases were HBeAg and anti-HBe negative, two of them were PCR positive. The detection of anti-HBe viremic cases in the present series suggest that preC variants could occur in our country. In conclusion, the integrated phase o f chronic hepatitis B seems to be less frequent than it was assumed, when only HBeAg or dot blot hybridization techniques were used. The new term "low replication phase" might favorably replace the former "integrated phase".