Prospective comparison of high-dose plateletpheresis with the latest apheresis systems on the same donors

BACKGROUND: To improve productivity of automated platelet (PLT) collection, the industry has introduced new instruments or modifications to existing equipment. STUDY DESIGN AND METHODS: With the same 8 donors for double (DDC) and triple-dose PLT collection (TDC), the Baxter Amicus (AM), the Haemonetics MCS Plus (MCS+), and the Gambro Trima Accel (TA) were evaluated focusing on yield, duration, and citrate donor load. Target endpoints were set at 5.5 x 10(11) to 6.0 x 10(11) PLTs (DDC) and 7.5 x 10(11) to 8.0 x 10(11) PLTs (TDC) in up to 100 and 120 minutes' donation time, respectively. RESULTS: TA was the most efficient system (74.5 +/- 3.9%) with significant differences from AM (71.1 +/- 3.9%; p = 0.028) and MCS+ (64.0 +/- 7.7%; p = 0.002). TA had advantages over AM for collection rate (10.9 x 10(9) +/- 2.2 x 10(9) vs. 10.1 x 10(9) +/- 1.5 x 10(9) PLTs/min; p = 0.382), whole blood processed (3928 +/- 611 mL vs. 4219 +/- 727 mL; p = 0.382), and time to obtain an established standard dose (TSD 2.5(EU), 30.2 +/- 5.6 vs. 37.7 +/- 5.5 min; TSD 3.5(US), 42.2 +/- 7.8 min vs. 52.7 +/- 7.7 min; p = 0.015), whereas AM was slightly superior in PLT yield (2.81 x 10(11) +/- 0.21 x 10(11) vs. 2.76 x 10(11) +/- 0.31 x 10(11)/unit; p = 0.645). Owing to the lowest draw (42.3 +/- 3.2 mL/min; p < 0.001) and collection rates (6.0 x 10(11) +/- 1.5 x 10(11)/min; p = 0.021), MCS+ was the slowest significantly (p < 0.001) but compensated with fewer citrate reactions owing to lower citrate infusion rates (0.78 +/- 0.11 mL/min/L; p = 0.028). CONCLUSION: High-dose plateletpheresis was performed efficiently and safely with all three instruments. AM had advantages in PLT yield, and MCS+, in donor comfort. TA was the fastest in obtaining an established standard dose and, because of this advantage, the machine with the highest practical impact in routine use.     

Targeting retinal and choroid neovascularization using the small molecule inhibitor carboxyamidotriazole

Neovascular ocular diseases as exemplified by proliferative diabetic retinopathy (PDR), exudative age-related macular degeneration (AMD), and retinopathy of prematurity (ROP) are severe diseases affecting all age groups in the US. We asked whether a small molecule, carboxyamidotriazole (CAI) known for its anti-angiogenic and anti-tumor effects and its ability to be administered orally in humans, could have anti-angiogenic effects in ocular in vitro and in vivo angiogenesis models. The anti-proliferative effects of CAI were examined by BrdU incorporation using human retinal and dermal endothelial cells and human pigment epithelial cells. The effect of CAI was determined using the Matrigel tube formation assay. The mouse model of choroidal neovascularization (CNV) initiated by laser rupture of Bruch's membrane was used to quantify in vivo effects of aqueous beta-hydroxypropyl cyclodextrin (bHPCD) formulations of CAI on neovascularization. The pharmacokinetics (PK) of CAI after intravitreal administration of bHPCD-CAI was studied in rabbit. The intravitreal toxicology of bHPCD-CAI was also examined in rat ocular tissue. We observed that CAI treatment of human endothelial cells decreased cell proliferation in a dose-dependent manner. In the in vivo tests bHPCD-CAI treatment reduced choroidal neovascular lesion volume, also in a dose-dependent manner. The intravitreal PK of bHPCD-CAI demonstrated that highly efficacious concentrations of CAI are reached in the vitreous compartment. No ocular toxicology was observed with intravitreous injection of CAI. These studies support the potential of developing intravitreal CAI in an bHPCD ocular formulation for treatment of proliferative retinopathies in humans.     

Predictors of engagement in the Alcoholics Anonymous group or to psychotherapy among Brazilian alcoholics

Objective To ascertain factors associated with engagement of patients with alcohol dependence in Alcoholics Anonymous (AA) groups and psychotherapy. Methods About 300 hospitalized alcoholics were interviewed at hospitalization and again 3 and 6 months thereafter. Assessment included the administration of standardized instruments. Determinants of engagement in both interventions were assessed through logistic regression analysis. Results Higher educational level was predictive of engagement in AA after 6 months (OR = 2.19; CI 1.08–4.41). Engagement in psychotherapy after 6 months was related to having a university degree (OR = 3.60; CI 1.6–7.9), to a co-morbid depressive disorder (OR = 3.47; CI 1.8–6.5), to the use of other drugs together with alcohol (OR = 3.08; CI 1.5–6.19), to previous treatment (OR = 2.87; CI 1.29–6.40), and to having a high school degree (OR = 2.44; CI 1.24–4.80). The presence of substance-induced anxiety disorder was associated with non-engagement in psychotherapy (OR = 0.27; CI 0.63–0.003). Conclusion The identification of predictors of engagement is important to guide clinicians in the choice of the treatment strategies that are more likely to be successful.     

Hypericum caprifoliatum (Guttiferae) Cham. & Schltdl.: a species native to South Brazil with antidepressant-like activity

In this work, previously published and unpublished results on biological activity of Hypericum caprifoliatum, a native species to South Brazil, are presented. Lipophilic extracts obtained from this species showed an antidepressant-like activity in mice and rat forced swimming test. Results from in vivo experiments suggest an effect on the dopaminergic transmission. Besides that, in vitro experiments demonstrated that the extract and its main component (a phloroglucinol derivative) inhibit monoamine uptake in a concentration-dependent manner, more potently to dopamine, but this effect is not related to direct binding at the uptake sites. It was also observed that a 3-day treatment with lipophilic extract prevents stress-induced corticosterone rise in mice frontal cortex but not in plasma. The lipophilic and methanolic H. caprifoliatum extracts also demonstrated antinociceptive effect, which seems to be indirectly mediated by the opioid system. These results indicate that H. caprifoliatum presents a promising antidepressant-like effect in rodents which seems to be related to a mechanism different from that of other classes of antidepressants.     

Involvement of nitric oxide in clonidine-induced spinal analgesia

BACKGROUND: The chronic pain relieving effects following spinal administration of clonidine are probably connected to alpha2-adrenoreceptor-induced augmented synthesis of nitric oxide (NO) in the spinal cord. In contrast, when acute pain is considered, the possible role of NO is still speculative. The aim of the present study was to explore the role of NO in acute pain relief following intraspinal administration of clonidine. METHODS: We used the mouse tail-flick model of acute pain. Spinal injections of the following agents and their combinations were administered: clonidine, L-arginine (NO precursor), the NO production inhibitor nitro-L-arginine-methyl ester (L-NAME), the NO antagonist methylene blue (MB) and nitroglycerine (NO releasing agent). RESULTS: A 95% analgesic response was achieved with 2.0 microg clonidine. L-Arginine produced analgesia, and L-arginine administration followed by clonidine resulted in a pronounced synergistic analgesic effect. This synergistic effect was attenuated by L-NAME. Pre-treatment with MB decreased and nitroglycerine administration did not affect the clonidine-induced analgesia. CONCLUSIONS: NO may be involved in the mediation of the acute pain relieving effects of intraspinally administered clonidine. Further research is warranted to establish the potential benefits and possibility for incorporation of NO promoting agents in therapeutic regional pain regimens.     

Pathogenic basis of treatment in children with bronchial asthma and gastroesophageal reflux

The relationship between bronchial asthma (BA) and gastro-esophageal reflux (GER) impose to study by frequency, reciprocally prognosis and therapeutics difficulty. Coexistence of both diseases is suggested by presence of asthmatics symptoms in non-atopic patients, difficult control and resistance of the specific treatment of asthma disease, worsening of respiratory symptoms in circumstances which favored GER. Pathogenetic relationship between BA and GER in children is the result of the associations- digestive particularity and: esophago-bronchial neurogenic mechanism produced by micro-aspiration , genetic or obtained inflammations development by commune Th2 mediators, medications effects. Classical treatments (H2-inhibitors, prokinetics agents, inhibitors of protonic pumps) is associated of the antiasthmatics "controller" therapy and in the future, anti-cytokine and anti-receptor therapy.     

Prognosis of spontaneous echocardiographic contrast in the thoracic aorta

The aim of this study was to assess the predictive value of spontaneous echocardiographic contrast (SEC) detected in the thoracic aorta by transesophageal echocardiography (TEE) on intermediate-term cardiovascular morbidity and mortality. We studied 299 consecutive patients (aged 61 +/- 13 years) without aortic aneurysm or dissection, who underwent TEE in 1995 to 1996. Cardiovascular deaths and nonfatal events were recorded over a period of < or = 60 months. Left ventricular function was classified as preserved versus depressed according to ejection fraction values (>40% vs < or = 40%) on 2-dimensional echocardiography. SEC was identified in 35 patients (11.7%). During follow-up, 66 patients died (36 deaths were due to cardiovascular causes; 10 and 26 cardiovascular deaths occurred in patients with and without SEC, respectively [p <0.001]). Survival time was significantly reduced in patients with versus without SEC (28 +/- 18 vs 39 +/- 19 months, p = 0.0012). Multivariate analysis revealed that the presence of SEC doubled the odds for cardiovascular death and for the combined end point of cardiovascular death and events. There was a significant difference in survival distributions between patients with and without SEC between both genders (p <0.001). In patients with normal or mildly reduced left ventricular function, SEC was predictive of an adverse outcome, whereas this was not the case in patients with more severely depressed cardiac function. It is concluded that the presence of SEC in the thoracic aorta is associated with a high risk of cardiovascular events and/or death over intermediate-term follow-up.     

Systemic lupus erythematosus in children. I: clinical and age dependent evolutive characteristics

The individualized, retrospective study of 14 children with SLE (4-16 years) pointed out a series of clinical and age dependent evolutive characteristics. Below the age of 10 years old (lot 1:2 boys and 4 girls), SLE started as a prolonged fever syndrome (5-16 weeks) in the majority of cases; for 2 children the severe poliarthritis resistant to the AINS therapy is associated with the durable absence of the antinuclear seric antibody (ANA). For the same age group a high frequency of neurological manifestations (5/6 cases) was noticed. After the age of 10 years old (lot II: 8 girls) the symptoms incidence at debut is close to the one of the adult, the cutanat and renal manifestations in evolution were dominant (7/8 cases). The 7 months absence of ANA characterises a case that started with hepatomegaly, severe neurological and physiological manifestations and microscopic hematuria. The follow-up lasted until the age of 16 years old; the patients were clinically tested for severe renal complication. The correct application of the classical criteria of diagnostic (ARA, 1982), and in the last few years the application of the ponderat score (Mayer, 1998), allows us to establish an early diagnostic and a rapid evaluation of a relapse, therefore influencing the treatment.     

Combined grading for choroidal neovascularisation: colour,fluorescein angiography and autofluorescence images

BACKGROUND: Patients with age-related macular degeneration (ARMD) have several imaging techniques carried out regularly. In this study we introduce a new grading model of autofluorescence images (AF), compare it with fluorescein angiography (FFA) and digital colour fundus photos (COL) and test for inter- and intraobserver reliability. METHODS: A total of 71 eyes of 54 patients with bilateral or unilateral CNV had COL, FFA and AF, fulfilling the inclusion criterion of having all 3 types of imaging carried out on the same day or within 14 days. The grading of COL was performed by a trained grader based on the International ARM classification; FFA and AF images were independently graded by two trained retinal specialists in order to assess inter-observer reliability. Overall, 30% of all images were regraded after at least 14 days interval to assess intra-observer variability. RESULTS: The intergrader agreement was exact for classification of CNV (k = 1.00); almost perfect for FFA features (k = 0.83) and correspondence of decreased AF to COL (k = 0.94); substantial for patterns of decreased and increased AF (k = 0.80, k = 0.78), correspondence of patterns of increased AF to FFA and to COL (k = 0.78, k = 0.74) and background AF (k = 0.72); moderate for CNV diameter in FFA (k = 0.45), FFA pattern (k = 0.43), dimension of increased and decreased AF (k = 0.5, k = 0.56); fair for quality of FFA and AF images (k = 0.21, k = 0.26) respectively. The intragrader agreement varied from exact to substantial for all categories. Diffuse and reticular patterns of decreased AF and reticular pattern of increased AF correlated well, with visual acuity worse than 6/24. CONCLUSION: The combined grading system was reliable for evaluating the three imaging techniques, and might be suitable for epidemiological studies and therapeutic trials where such grading is warranted. Certain AF patterns seem to predict VA outcome better than one might have predicted based on FFA. Further studies are needed to evaluate its usefulness in clinical settings for predicting outcomes for patients receiving therapy for end-stage disease.