Incidence and spatial distribution of adult-onset primary malignant and other central nervous system tumors in Southern Sardinia,Italy

Neurological Sciences - To study for the first time the incidence of adult-onset CNS tumors in Southern Sardinia, Italy. Clinical records of patients > 18 years old who...     

Clinical aspects of induced hypothermia in full term neonates with perinatal asphyxia

Moderate hypothermia is a novel neuroprotective therapy for full term neonates with severe perinatal asphyxia. Although the therapy appears to be safe, admission to a level III neonatal intensive care unit of these patients is justified. Potential complications include hypotension, tube obstruction due to sticky secretions, severe bradycardia, and thrombocytopenia. Furthermore, doses of commonly used drugs such as sedatives, anticonvulsants and antibiotics should be adjusted during hypothermia and on rewarming, and should be monitored carefully. Further studies aiming at optimizing onset, duration, and depth of hypothermia in neonates are necessary. Combination of hypothermia with drugs may further improve neuroprotection in asphyxiated full term neonates.     

Multidisciplinary allocation of chronic pain treatment: Effects and cognitive‐behavioural predictors of outcome

Objectives . Multidisciplinary treatment approaches have been found to be effective for chronic pain patients although there are large individual differences in outcomes. To increase overall treatment effects, tools are needed to identify patients most likely to benefit from tailored, comprehensive modular treatment schemes. Design . The present study evaluates the effects of a multidisciplinary pain treatment allocation protocol in chronic pain patients and seeks to identify cognitive‐behavioural predictors of outcome. Pain intensity, functional disability, depression, and use of medication in an intervention group of 110 chronic pain patients were compared to the outcomes of a 110 strong control group. Results . Paired pre‐ and post‐treatment t tests showed that all primary outcomes had significantly decreased in the intervention group with ANCOVAs revealing a main group effect for post‐treatment pain intensity levels and functional disability. Paired t tests demonstrated both variables to have significantly reduced after treatment relative to the levels reported by the control group. Predictor analyses further showed higher levels of acceptance to significantly predict larger reductions in pain intensity in the intervention but not in the control group. Conclusion . The tested multidisciplinary allocation scheme for out‐patient treatment of chronic pain complaints was effective in reducing pain intensity and functional disability. Findings also showed that especially those patients that are able to accept their condition are likely to profit most from the treatment in terms of pain reduction.     

Leakage of decision uncertainty into movement execution in Parkinson’s disease?

The concept of segregated basal ganglia–cortical loops entails that functional disturbances may result from abnormal processing within loops, but also from abnormal communication between loops. Cognitive and motor processes subserved by different basal ganglia–frontal loops may interfere with one another as a result of such abnormal communication, leakage, between loops. In Parkinson’s disease, movement execution has been found susceptible to decision uncertainty, attributed to this mechanism. Here, we evaluate whether this mechanism of abnormal coupling or leakage extends to perceptual decision-making with trial-by-trial control of decision uncertainty. We examined 10 Parkinson’s disease (PD) patients and healthy control subjects in a random-dot motion direction discrimination task with concurrent EEG recording. Random-dot motion was manipulated to make direction discrimination easy or difficult. Reaction times (RT) and movement times (MT) were recorded, and EEG was analysed to extract movement-related potentials. Easy versus difficult direction discrimination produced robust, equally large RT differences in patients and controls (>400 ms), along with a marked difference in error rates, confirming the efficacy of the task. Effects of easy versus difficult discrimination on MT were comparatively small (<50 ms) and did not differ between groups, despite robustly slower MT in patients. Lateralised movement-related EEG potentials reproduced the MT difference between patients and controls. Together, the results do not demonstrate an enhanced effect of decision uncertainty onto movement execution in PD. We surmise that leakage of decision uncertainty into movement execution is probably task-dependent, consistent with the view that the degree to which partial information is allowed to influence the motor system is under strategic control.     

Results of macular pucker surgery: 1- and 5-year follow-up

Background  Although macular pucker removal in patients with metamorphopsia due to a macular pucker is a traditional elective vitreoretinal indication, we found that patients were not uniformly satisfied after surgery. We wished to study outcome in vision and metamorphopsia in patients undergoing macular pucker surgery, to assess changes between 1- and 5-year follow-up, as well as patient satisfaction at 5 years. Methods  We assessed 107 consecutive patients undergoing macular pucker surgery and subsequent cataract surgery when not already pseudophakic. Early Treatment of Diabetes Study (EDTRS) vision and Sine Amsler Chart metamorphopsia grading were assessed before surgery and 1 year postop in 107 patients. In 57 patients we obtained a 5-year vision, metamorphopsia grading and a response to a questionnaire. Results  After 1 year, mean vision had improved 2 ETDRS lines and metamorphopsia had decreased in 83% of the patients. The 57 patients returning for the 5-year follow-up and questionnaire had a statistically significantly greater improvement in vision at 1 year than those who did not return. In these 57 patients, a further mean increase of 1 ETDRS line had occurred, as well as a further decrease in metamorphopsia in one third of the patients. Forty of 57 patients (70%) indicated that they would elect to have surgery again. Reasons for not returning after 5 years, however, were probably related to dissatisfaction in at least one third of patients. Conclusions  Although macular pucker surgery resulted in an increase in vision and a decrease of metamorphopsia in 83% of patients after 1 year, we assume, based on the biased patient sample we questioned after 5 years, that subjective assessment would be positive in only a small majority of the patients.     

Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides

In a search for natural proteins with anti-HIV activity, we screened a large set of purified proteins from bovine milk and peptide fragments thereof. Because several charged proteins and peptides are known to inhibit the process of virus entry, we selected proteins with an unusual charge composition or hydrophobicity profile. In contrast with some chemically modified (strongly negative) milk proteins, unmodified alpha(s2)-, beta- and kappa-casein, as well as several negatively and positively charged fragments thereof, did not show significant inhibition of virus replication. In fact, HIV-1 replication was elevated in the presence of beta-casein or amphiphilic fragments thereof. Bovine lactoferrin (bLF), a milk protein of 80 kDa, showed considerable inhibitory activity against HIV-1 with an IC50 of 0.4 microM. Modest inhibition was obtained with lactoferricin, a highly positively charged loop domain of bLF, indicating that other domains within the native bLF protein may also be required for inhibition. bLF blocked HIV-1 variants that use either the CXCR4 or the CCR5 coreceptor. In order to obtain further insight into the mechanism of action of this antiviral protein, we selected a bLF-resistant HIV-1 variant. The bLF-resistance phenotype is mediated by the viral envelope protein, which contains two interesting mutations that have previously been associated with an altered virus-host interaction and a modified receptor-coreceptor interaction. These results demonstrate that bLF targets the HIV-1 entry process.     

The influence of charge clustering on the anti-HIV-1 activity and in vivo distribution of negatively charged albumins

The substitution of human serum albumin with negatively charged molecules, such as succinic acid (Suc-HSA) or aconitic acid (Aco-HSA), resulted in proteins with potent anti-HIV activities, by binding to viral gp120 (V3 loop). The aim of the present study was to investigate whether the distribution of negative charges on the albumin backbone influences the anti-HIV activity. Therefore, we prepared albumins with clusters of negatively charged groups by coupling of heparin. The effects of this substitution on anti-HIV activity, in vivo distribution and the protein structure as compared to random succinylation were assessed. In vitro studies indicated that HSA-modified with heparin 6 or 13 kD displayed anti-HIV activity (IC50=660 and 37 nM, respectively) and exhibited affinity for gp120-V3 loop, although the activity was lower than that of Suc-HSA. Combined derivatization of HSA with heparin 13 kD and aconitic acid groups resulted in significantly increased inhibitory actions (IC50=2.8 nM). Structural analysis showed that modification of HSA with heparin did not lead to extensive unfolding of the protein, meaning that these modified proteins were still globular in structure. In contrast, succinylation of HSA resulted in a highly randomly coiled conformation. Dynamic light scattering experiments revealed that, at neutral pH, the heparin fragments attached to the protein were wrapped around the molecule rather than sticking out into the solution. In conclusion, coupling of sufficient clustered negative charges, by coupling of Hep-fragments, on HSA resulted in a clear anti-HIV activity of the protein. Yet, random distribution of anionic groups in the albumin seemed more optimal for in vitro anti-HIV activity. The higher plasma and lymphatic concentrations of Hep-HSA compared to Suc-HSA seemed more favorable for an anti-HIV activity in vivo.     

Immature articular cartilage is more susceptible to blood-induced damage than mature articular cartilage: an in vivo animal study

OBJECTIVE: Cartilage of young but skeletally mature dogs is more susceptible to blood-induced damage than that of old dogs. The aim of the present study was to investigate whether cartilage of skeletally immature individuals is even more adversely affected by exposure to blood than that of mature individuals, as suggested by clinical practice experience with humans. METHODS: Right knees of 3 groups of 6 beagle dogs (skeletally immature, young mature, and old animals) were injected with autologous blood on days 0 and 2. On day 4, cartilage matrix proteoglycan turnover (content, synthesis, and release), synovial inflammation, and cartilage-destructive properties of the synovial tissue were determined and compared with those of the left uninjected control knees. RESULTS: Subsequent to intraarticular bleeding, cartilage proteoglycan content decreased in an age-dependent manner, with the largest decrease occurring in cartilage of immature animals. Proteoglycan synthesis per cell also decreased in an age-dependent manner, with the largest decrease occurring in the immature animals. Cartilage proteoglycan release increased in all 3 groups, but the decrease was not age dependent. Interestingly, immature animals showed a large increase in cartilage DNA content upon exposure to blood, whereas mature animals did not. Histologic analysis showed a mild synovitis in animals of all ages, but catabolic inflammatory activity was found only in immature animals. CONCLUSION: Joints of skeletally immature dogs appeared to be more susceptible than joints of mature dogs to the adverse effects of a joint hemorrhage. These data suggest that for humans, specifically young children are at risk for joint damage after a joint hemorrhage.