Predictability and inconsistencies in the cognitive outcome of early treated PKU patients

Long-term cognitive outcome and treatment of adult early treated (ET)PKU patients is a main issue in PKU research. We questioned whether the intellectual development of ETPKU patients is stable and to what extent its variation may be predicted by the quality of metabolic control. The aims of the present longitudinal retrospective study were to assess in young adult ETPKU patients: i) the relationship between IQ and metabolic control during the first two decades of life; and ii) the intra- and interindividual variability in the developmental trajectory which cannot be predicted by the disease’s biomarkers. We collected biochemical data from 65 ETPKU patients (diagnostic blood Phe > 360 μmol/l) who were assessed twice for IQ (Wechsler Intelligence Scale) during their lifetime (mean age: 10.2 and 19.6 years, respectively). Results show that in ETPKU patients IQ over the second decade of life remained stable in about half of the patients (51%); while the rest experienced a gain (7 to 15 points) or loss (7 to 28 points) in IQ scores (23 and 26% respectively) whatever the quality of metabolic control was. The main factor affecting the second IQ was the value of the first IQ (p < 0.000) whose effect overruled that of the markers of metabolic control. Looking at the developmental trajectory of our ETPKU patients, the present study disclosed a remarkable interindividual variability in their cognitive outcome and also an inconsistent linkage between cognitive performances and biochemical control, thus supporting the hypothesis of an individual resilience or vulnerability to Phe in young adult ETPKU.     

A double-blind, randomised, vehicle-controlled clinical study to evaluate the efficacy of MAS065D in limiting the effects of radiation on the skin: interim analysis

Our aim was to assess the efficacy of MAS065D, a non-steroidal water-in-oil cream, in preventing and limiting skin reactions caused by radiation therapy (RT). 40 women treated with conservative breast cancer surgery followed by radiotherapy, were randomised to receive MAS065D (22 pts) or vehicle (18 pts). Radiotherapy was delivered in 20 fractions: 2.25 Gy to the whole breast plus a concomitant boost of 0.25 Gy to the tumour bed up to a total dose of 50 Gy. Evaluations of skin toxicity, erythema, and subjective symptoms were carried out weekly and 3 weeks after treatment completion. A statistically significant difference between vehicle and MAS065D groups was recorded regarding the maximum severity of skin toxicity (p < 0.0001), burning within the radiation field (p = 0.039) and desquamation (p = 0.02), in favour of the latter. We conclude that MAS065D may be considered a safe and effective treatment in the prevention and minimization of skin reactions and associated symptoms.     

Administration of minor polar compound-enriched extra virgin olive oil decreases platelet aggregation and the plasma concentration of reduced homocysteine in rats

We investigated the effect of extra virgin olive oil (EVOO) on platelet aggregation and plasma concentrations of homocysteine (Hcy) redox forms in rats in relation to the minor polar compound (MPC) concentration of EVOO. We used 3 olive oil samples with similar fatty acid but different MPC concentrations: refined olive oil (RF) with traces of MPC (control oil), native EVOO with low MPC concentration (LC), and EVOO with high MPC concentration (HC) enriching LC with its own MPC. Oil samples were administered to rats by gavage (1.25 mL/kg body weight) using 2 experimental designs: acute (24-h food deprivation and killed 1 h after EVOO administration) and subacute (12-d treatment, a daily dose of oil for 12 d, and killed after 24 h of food deprivation). Platelet aggregation was induced by ADP (ex vivo tests) and a reduction in platelet reactivity occurred in cells from rats given LC in the subacute study and in cells from rats administered HC in both studies as indicated by an increase in the agonist half maximal effective concentration. HC inhibited platelet aggregation induced by low ADP doses (reversible aggregation) in cells of rats in both the acute and subacute studies, whereas LC had this effect only in the subacute experiment. Moreover, in rats administered HC in both experiments, the plasma concentration of free reduced Hcy (rHcy) was lower and Hcy bound to protein by disulfide bonds (bHcy) was greater than in RF-treated rats. bHcy was also greater in rats given LC than in RF-treated rats in the subacute experiment. Plasma free-oxidized Hcy was greater in rats given LC and HC than in those administered RF only in the subacute experiment. In conclusion, these results show that MPC in EVOO inhibit platelet aggregation and reduce the plasma rHcy concentration, effects that may be associated with cardiovascular protection.     

Use of color charts for the diagnosis of finger whiteness in vibration-exposed workers

Objectives

To assess the usefulness of color charts for the diagnosis of finger whiteness in vibration-exposed workers.

Methods

A group of 146 forestry and stone workers exposed to hand-transmitted vibration (HTV) were examined twice over 1 year follow up period. The anamnestic diagnosis of finger whiteness was made on the basis of (a) a medical history alone, and (b) the administration color charts which showed changes in the skin color of fingers and hands. The cold response of digital arteries was assessed by measuring the change in finger systolic blood pressure (FSBP) after local cooling from 30 to 10°C (FSBP%_10°).

Results

Assuming the administration of color charts as the gold standard, the sensitivity and specificity of the medical history alone to diagnose finger whiteness was 88.2 and 93.8%, respectively, at the initial cross-sectional study and 94.4 and 97.7% at the end of the follow-up. Random-intercept linear regression analysis of follow up data showed that after adjustment for several covariates, FSBP%_10° was significantly associated with finger whiteness assessed by either medical history alone (P < 0.005) or the color charts (P < 0.001). However, a statistical measure of overall fit of regression models (Bayesian Information Criterion) suggested that the color chart method performed better than medical history alone for the prediction of the cold response of digital arteries.

Conclusion

The administration of color charts seems to reduce the proportion of false positive responses for finger whiteness in a population of vibration-exposed workers. The color chart method was a more significant predictor of digital arterial hyperresponsiveness to cold than medical history alone. These findings suggest that the use of color charts in clinical and epidemiological studies may be of help to assist in the diagnosis of finger whiteness in vibration-exposed workers.