Child health and the environment: the INMA Spanish Study

The INMA (INfancia y Medio Ambiente [Environment and Childhood]) is a population-based cohort study in different Spanish cities, that focuses on prenatal environmental exposures and growth, development and health from early fetal life until childhood. The study focuses on five primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) asthma and allergies; (4) sexual and reproductive development; and (5) environmental exposure pathways. The general aims of the project are: (1) to describe the degree of individual prenatal exposure to environmental pollutants, and the internal dose of chemicals during pregnancy, at birth and during childhood in Spain; (2) to evaluate the impact of the exposure to different contaminants on fetal and infant growth, health and development; (3) to evaluate the role of diet on fetal and infant growth, health and development; and (4) to evaluate the interaction between persistent pollutants, nutrients and genetic determinants on fetal and infant growth, health and development. Extensive assessments will be carried out on 3100 pregnant women and children. Data will be collected by physical examinations, questionnaires, interviews, ultrasound and biological samples. Pregnant women are being assessed at 12, 20 and 32 weeks of gestation to collect information about environmental exposures and fetal growth. The children will be followed until the age of 4 years.     

Oral methylphenidate challenge selectively decreases putaminal T2 in healthy subjects

Despite the recent rise in oral methylphenidate (MPH) abuse, few studies have characterized the time course of oral MPH brain effects in human subjects. Accordingly, this study assessed the hemodynamic effects of oral MPH effects in 11 healthy young adults (six women), by measuring brain transverse relaxation times (T2). T2 can be interpreted as a surrogate marker for, and inversely correlated with, steady-state cerebral blood volume (CBV). Data were acquired from the caudate nucleus, putamen, and thalamus, using a 1.5 T MRI scanner at baseline and serially for 2 h following oral MPH administration (0.5 mg/kg). Physiological and subjective measures and plasma MPH levels also were examined. MPH induced a selective T2 decrease (-1.65+/-0.53 ms) in the putamen (F(6,54)=2.68, P<0.03). Heartrate, blood pressure and plasma MPH levels increased significantly after drug administration, as well as subjective ratings of "feeling drug effect". T2 decreases may reflect MPH-induced increases in putaminal blood volume. These data suggest that T2 relaxometry can be used to study the time course of regional cerebral blood volume responses to MPH and perhaps to other stimulant drugs.     

Pharmacy data for tuberculosis surveillance and assessment of patient management

Underreporting tuberculosis (TB) cases can compromise surveillance. We evaluated the contribution of pharmacy data in three different managed-care settings and geographic areas. Persons with more than two anti-TB medications were identified by using pharmacy databases. Active TB was confirmed by using state TB registries, medical record review, or questionnaires from prescribing physicians. We identified 207 active TB cases, including 13 (6%) missed by traditional surveillance. Pharmacy screening identified 80% of persons with TB who had received their medications through health plan-reimbursed sources, but missed those treated solely in public health clinics. The positive predictive value of receiving more than two anti-TB medications was 33%. Pharmacy data also provided useful information about physicians' management of TB and patients' adherence to prescribed therapy. Pharmacy data can help public health officials to find TB cases and assess their management in populations that receive care in the private sector.     

Functional predictors of school participation by children with disabilities

This study examined the functional requirements that significantly predicted participation of US elementary school children with a variety of disabling conditions (N = 266), in seven different school settings: Transportation, Transitions, Regular classroom, Special classroom, Mealtime, Bathroom, and Playground. Performance on a number of setting-relevant tasks was expected to be predictive of meaningful participation in each school environment. Stepwise multiple regression analyses were conducted to identify the order of importance of the relevant variables as well as the smaller set of functional tasks that best predicted children's participation in each setting. The results revealed that successful participation in the different elementary school settings was strongly associated with performance of both physical and cognitive/behavioural activities. Furthermore, each setting had a unique set of predictors, suggesting that some aspects of function are context-specific. Findings from this study may inform therapists about the most relevant areas of function that support social and physical participation of children with disabilities who are included in regular schools.     

Temporal performance fields: visual and attentional factors

This study is the first to investigate: (a) 'temporal performance fields,' whether the speed of information accrual differs for different locations at a fixed eccentricity, and (b) whether covert attention modulates temporal dynamics differentially at isoeccentric locations. Using the speed accuracy tradeoff (SAT) procedure, we derived conjoint measures of how isoeccentric locations and precueing targets location affect speed and accuracy in a search task. The results demonstrate the existence of temporal performance fields, analogous to spatial performance fields: information accrual was fastest for target on the horizontal meridian, intermediate for targets at the intercardinal locations, slow for targets on the vertical meridian, and slowest for targets at the North (N) location (accrual time pattern: E&WS>intercardinal>E&W). Hence, the compensatory effect of attention eliminated the temporal asymmetries across isoeccentric locations.     

Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin

Rosiglitazone and atorvastatin combination therapy has beneficial effects on both glycemic control and plasma lipid levels in type 2 diabetic patients. In the present study, we sought to determine whether this combination can also exert direct antiatherosclerotic effects in macrophages. Our results show that 2 microM rosiglitazone, alone or combined with 5 microM atorvastatin, significantly upregulated the expression of the ATP-binding cassette transporter ABCA1 and of the class B scavenger receptor CLA-1 (CD36 and LIMPII analog), both involved in cholesterol efflux from macrophages. On the other hand, the combination with atorvastatin attenuated the inductive response elicited by rosiglitazone alone on CD36 mRNA (34%, P < 0.05) and protein (16%, P < 0.05), while the uptake of oxidized low density lipoprotein (LDL) remained unaffected. When we examined the effects of the drugs on acetyl-LDL-induced cholesterol accumulation, we found that only the combination of atorvastatin with rosiglitazone caused a net depletion in the cholesteryl ester content of macrophages (35%, P < 0.05). Our data suggest that this reduction was not mediated by effects on proteins that regulate cholesterol flux, but it may be related to the inhibition of cholesteryl ester formation elicited by the statin.     

Diagnosis of infection of implantable central venous catheters by [18F]fluorodeoxyglucose positron emission tomography

OBJECTIVE: The aim of this study was to evaluate the role of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the diagnosis of infection of implantable vascular catheters. METHODS: We evaluated six patients with haematological cancer and infection of their implantable vascular catheter and who underwent FDG PET imaging around the time of their infection. RESULTS: Six patients with multiple myeloma who developed infection of their implantable device (five port pocket infections and one tunnel infection) were identified. FDG PET revealed increased uptake at the site of the implantable catheter (SUV 2.7-4.5) in all six patients, even in the absence of signs or symptoms of infection at the site of the device (three), and the presence of severe neutropenia (four). The three patients who did not have local inflammation at the site of the device were profoundly neutropenic. The FDG PET diagnosis led to removal of the device in two patients. CONCLUSION: FDG PET is a safe, rapid and accurate tool for diagnosing infection of an implantable catheter, including among those patients not exhibiting local signs and symptoms of infection, and in whom the diagnosis of infected device may be difficult. FDG PET may help prevent the unnecessary removal of implantable intravascular catheters and the unwarranted use of antibiotics.     

Laparoscopic laser soldering for repair of ureteropelvic junction obstruction in the porcine model

BACKGROUND AND PURPOSE: Laparoscopic pyeloplasty is used for the repair of ureteropelvic junction (UPJ) obstruction. Our objective was to introduce laser soldering to this procedure. MATERIALS AND METHODS: We developed a system based on a CO2 laser, an infrared detector, and two infrared transmitting optical fibers to obtain temperature-controlled laser soldering of cuts in tissues. The system was used for laparoscopic soldering of incisions in the kidneys of pigs. RESULTS: We carried out laparoscopic pyeloplasty successfully in a porcine model using fiberoptic laser soldering. Laparoscopic laser soldering was found to be faster than suturing. It was easier to use and provided watertight bonding. CONCLUSIONS: This technique will be useful in pyeloplasty as well as other laparoscopic surgical procedures.     

Structural characterization of an etheno-2'-deoxyguanosine adduct modified by tetrahydrofuran

The reaction of 2'-deoxyguanosine with the alpha,beta-unsaturated aldehydes trans-2-octenal, trans-2-nonenal, trans-2-decenal, trans,trans-2,4-nonadienal, and trans,trans-2,4-decadienal in THF gives rise to three novel adducts: 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-[3-hydroxy-1-(3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-3,5-dihydro-imidazo[1,2-a]purin-9-one-7-yl)-propyl]-3,5-dihydro-imidazo[1,2-a]purin-9-one (A7) and 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-(tetrahydrofuran-2-yl)-3,5-dihydro-imidazo[1,2-a]purin-9-one (A8 and A9), which are not observed in the absence of THF. These adducts were isolated from in vitro reactions by reversed-phase HPLC and fully characterized on the basis of spectroscopic measurements. Adduct A7 consists of two 1,N2-etheno-2'-deoxyguanosine (1,N2-epsilon dGuo) residues linked to a hydroxy-carbon side chain; adducts A8 and A9 are interconvertible 1,N2-epsilon dGuo derivatives bearing a THF moiety. The proposed reaction mechanism involves the electrophilic attack on 1,N2-epsilon dGuo by the carbonyl of 4-hydroxy-butanal, generated via ring opening of alpha-hydroxy-THF (THF-OH), yielding adducts A8 and A9. A further combination of these adducts with another 1,N2-epsilon dGuo produces the double adduct A7. These findings demonstrate that reactions of unsaturated aldehydes in the presence of THF produce novel condensation 1,N2-epsilon dGuo-THF adducts. Further studies would indicate the relevance of these adducts in THF toxicity.     

Continuous infusion of oxaliplatin plus chronomodulated capecitabine in 5-fluorouracil- and irinotecan-resistant advanced colorectal cancer patients

OBJECTIVES: The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients. METHODS: 36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study. TREATMENT: Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1-14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well. RESULTS: Most frequent related G3-4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3-4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0-15.7 months), the median response duration 2.8 months (95% confidence interval 1.2-5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7-6.3 months). The 1-year survival rate was 53.8%. CONCLUSIONS: The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC.