Does age of onset of impairment impact on neuropsychological and personality features of adult ADHD?

The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n = 415) were evaluated in the ADHD outpatient program at Hospital de Clínicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two ages of onset groups (before 7; n = 209 or from 7 to 12 years; n = 206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively P = 0.016 and P = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria.     

Comparison of red blood cell membrane microstructure after different physicochemical influences: Atomic force microscope research

Purpose

After the influence of different actions on the blood, the erythrocytes may change their macrostructure. At the same time, the microstructure of cell membrane will be changed as well. This study provides the results of comparison of red blood cell membrane microstructure after they have been affected by different factors.

Materials and Methods

Images and spatial profiles of the cell surface were obtained by atomic force microscope. It was proposed to use spatial Fourier transform to decompose the initial complex profile into series of simple ones. This made it possible to compare surface parameters after exposure of red blood cells to different external actions.

Results

Quantitative differences between membrane profile harmonic composition parameters (amplitude and spatial period) after physical impact (impulse electrical field, osmotic swelling) and after chemical impact (the fixing fluid glutaraldehyde and the drug Esmeron) were experimentally confirmed.

Conclusions

Such experimental and theoretical approach may lay down the foundations of mechanisms of different factors' effect on red blood cells both in research and in clinics.     

Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala,Uganda

The World Health Organization recommends the use of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. The two most widely adopted ACT regimens are artemether (AR)-lumefantrine (LR) (the combination is abbreviated AL) and amodiaquine (AQ)-artesunate (AS). Pharmacokinetic (PK) data informing the optimum dosing of these drug regimens is limited, especially in children. We evaluated PK parameters in Ugandan children aged 5 to 13 years with uncomplicated malaria treated with AL (n = 20) or AQ-AS (n = 21), with intensive venous sampling occurring at 0, 2, 4, 8, 24, and 120 h following administration of the last dose of 3-day regimens of AL (twice daily) or AQ-AS (once daily). AS achieved an estimated maximum concentration in plasma (C_max) of 51 ng/ml and an area under the concentration-time curve from time zero to infinity (AUC_0-∞) of 113 ng·h/ml; and its active metabolite, dihydroartemisinin (DHA), achieved a geometric mean C_max of 473 ng/ml and an AUC_0-∞ of 1,404 ng·h/ml. AR-DHA exhibited a C_max of 34/119 ng/ml and an AUC_0-∞ of 168/382 ng·h/ml, respectively. For LR, C_max and AUC_0-∞ were 6,757 ng/ml and 210 μg·h/ml, respectively. For AQ and its active metabolite, desethylamodiaquine (DEAQ), the C_maxs were 5.2 ng/ml and 235 ng/ml, respectively, and the AUC_0-∞s were 39.3 ng·h/ml and 148 μg·h/ml, respectively. Comparison of the findings of the present study to previously published data for adults suggests that the level of exposure to LR is lower in children than in adults and that the level of AQ-DEAQ exposure is similar in children and adults. For the artemisinin derivatives, differences between children and adults were variable and drug specific. The PK results generated for children must be considered to optimize the dosing strategies for these widely utilized ACT regimens.Malaria is among Africa''s leading causes of morbidity and mortality, leading to an estimated 300 million to 660 million cases of Plasmodium falciparum malaria and approximately 1 million deaths per year (15, 30). In the recent past, the management of malaria primarily relied upon monotherapy with chloroquine (CQ) or sulfadoxine-pyrimethamine (SP). However, the widespread and excessive use of these agents led to drug resistance, and as a result, CQ and SP have limited roles in the treatment of malaria. The World Health Organization (WHO) currently recommends new artemisinin-based combination therapy (ACT) for the treatment of uncomplicated malaria in sub-Saharan Africa (38). ACT consists of a short-acting artemisinin derivative that rapidly reduces the parasite burden combined with a longer-acting partner drug that affords adequate treatment efficacy with 3 days of dosing (38). The most widely adopted ACT regimens in Africa are artemether (AR)-lumefantrine (LR) (the combination is abbreviated AL) and amodiaquine (AQ)-artesunate (AS), each of which is a first-line drug for the treatment of uncomplicated malaria in multiple African countries (37). As the availability of ACT increases, the use of hundreds of millions of doses is anticipated in Africa alone, especially by children, the group at the greatest risk for malaria (18).The artemisinins kill malaria parasites rapidly, and their excellent tolerability and safety provide an additional benefit (23). Resistance is also not a significant problem, although recent reports reveal the emergence of resistance in Southeast Asia (10). Both AS and AR are rapidly converted to the active metabolite dihydroartemisinin (DHA) by cytochrome P450 (CYP) enzymes, with DHA contributing the majority of the antimalarial activity (22, 33). Of the two drugs, AR is more lipid soluble and may exhibit erratic absorption (22). Artemisinins fail to reliably eliminate malaria infections after short courses of treatment if they are used alone. AQ, which is combined with AS, is a 4-aminoquinoline that is converted via CYP enzymes to the active metabolite desethylamodiaquine (DEAQ), which contributes the majority of the antimalarial activity (27). LR, which is combined with AL (Coartem), is an aryl aminoalcohol that is well tolerated (19, 35). The oral bioavailability of LR is highly variable and is dependent on administration with fatty foods; the level of exposure decreases 16-fold when LR is administered in a fasting state compared to the level of exposure achieved when it is administered with a fatty meal (12, 35).Pharmacokinetic (PK) studies of ACTs informing dosing guidelines have been limited to adults, with less information being available for children. Pediatric dosing of AL and AQ-AS are deduced from adult-based regimens adjusted for body weight, with little consideration of maturational effects on drug absorption and metabolism (6). Indeed, CYP-UDP-glucuronosyltransferase activity and clearance vary with age. Several clinical PK studies have reported that clearance and metabolism in prepubescent children are altered compared to clearance and metabolism in adults (17, 31). For example, for the antimalarial combination SP, PK data generated for children receiving standard weight-based dosing revealed lower levels in children than in adults (4). Importantly, a correlation between low SP levels and the risk of treatment failure has also been noted (32). Likewise, for LR, the levels measured at day 7 were lower in children than in adults (8), which may also compromise outcomes (26). As children are at high risk of severe morbidity with inadequate treatment of malaria, it is important to ensure appropriate dosing of ACTs in this group. We therefore determined the PK parameters for all components and major metabolites of the two most widely adopted ACT regimens in Africa in Ugandan children with acute uncomplicated malaria.     

Risk assessment and adjuvant systemic therapy in resected stage II colon cancer

Adjuvant chemotherapy following surgical resection of stage III colon cancer has become the standard of care based on numerous large randomized trials that have demonstrated benefit in overall survival. For patients with stage II colon cancer, the picture is more uncertain. Although clinical trials have not reported a significant survival benefit for adjuvant chemotherapy in stage II disease, patients with certain high-risk clinical and pathologic features may warrant postoperative treatment. Molecular markers, such as 18q loss of heterozygosity and mi crosatellite instability, may also help to prognosticate patients with stage II colon cancer, although data supporting their role have been largely retrospective. The role of these markers in stage II disease is being prospectively investigated. Continued enrollment in clinical trials and further risk stratification will help clarify the optimal management of patients with stage II colon cancer.