Diabetic retinopathy and its relevance to paediatric age. An update

Diabetic retinopathy is a frequent chronic complication of diabetes and may predict nephropathy and cardiovascular events. Development of proliferative lesions and/or macular edema indicates that a sight-threatening stage has been reached which, if left untreated, will almost inevitably evolve to blindness. Prevention of this feared outcome relies upon optimal control of blood glucose and, when hypertension is present, blood pressure. Besides, yearly screening by ophthalmoscopy and/or retinal photography should be carried out in all people with diabetes to identify those who have developed sight-threatening lesions. Though sight-threatening retinopathy is rarely reached during paediatric age, if anything because it takes many years to develop, the retina should be carefully monitored already during childhood and adolescence. "Florid" retinopathy and diabetic papillopathy are possible specific manifestations of retinopathy in diabetic patients during their early post-pubertal years. Pre-pubertal years, though suggested by some as protecting against diabetic retinopathy, may, in fact, contribute to and even be an independent risk factor for the development of proliferative lesions later in life. Apart from controlling glycaemia and blood pressure, ongoing phase 3 trials are evaluating new possible pharmacologic approaches to the prevention and treatment of retinopathy which, to this date, relies upon the hugely effective but destructive application of laser photocoagulation.     

Two-year follow-up of a smoking cessation trial in patients with schizophrenia: increased rates of smoking cessation and reduction

BACKGROUND: Long-term success rates of smoking cessation programs for patients with schizophrenia are unknown. This study, conducted between June 2001 and November 2002, evaluated the rate of smoking cessation and reduction in patients with schizophrenia (DSM-IV) 2 years after they had participated in a smoking cessation study in order to determine whether subjects who significantly reduced smoking during the original trial resumed their previous level of smoking at 2 years. METHOD: Two years following a double-blind placebo-controlled trial of bupropion sustained release, 150 mg/day, added to cognitive-behavioral therapy for smoking cessation in patients with schizophrenia, subjects were interviewed, medical charts were reviewed, and carbon monoxide in expired air was measured. RESULTS: Seventeen of 18 subjects completed the follow-up assessment. More subjects were abstinent (22% [N = 4]) at the 2-year follow-up than were abstinent at the end of the trial (6% [N = 1]). Subjects who achieved significant smoking reduction during the trial were more likely to be abstinent at 2 years (4/7) than those who did not significantly reduce smoking during the trial (0/11) (chi(2) = 8.1, p <.005). Most subjects who achieved > or = 50% reduction in smoking at the end of the trial maintained at least that level of reduction at 2 years. Smoking reduction during the treatment intervention was correlated with smoking reduction at follow-up (r = 0.60, p =.01). CONCLUSION: The results from this naturalistic study suggest that behavior changes achieved in smoking cessation programs for patients with schizophrenia may be durable and may predict future smoking behavior. We conclude that further investigation into the relationship between smoking reduction and future smoking cessation in special populations is indicated.     

Short-term brain atrophy changes in relapsing-remitting multiple sclerosis

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.     

Trait anxiety and nicotine dependence in adolescents: a report from the DANDY study

The Revised Children's Manifest Anxiety Scale (RCMAS) and the Hooked on Nicotine Checklist (HONC) were used to measure trait anxiety and tobacco dependence in a population of 581 adolescents. Smokers demonstrated higher mean RCMAS scores (9.3, S.D.=6.5) than nonsmokers did (7.4, S.D.=6.2, t=-3.7, P<.001). Participants with symptoms of tobacco dependence had higher RCMAS scores (mean=11.6, S.D.=6.0, n=115) than did the participants without symptoms (mean=7.8, S.D.=6.0, n=177, t=-5.3, P<.001). Scores on the RCMAS and the HONC correlated positively (n=292, r=.32, P<.001). Participants who had felt relaxed in response to their first exposure to nicotine were also more likely to develop dependence and to report that stress caused cravings or a need to smoke. Trait anxiety and relaxation in response to the first dose of nicotine were unrelated and appear to be independent risk factors for the development of nicotine dependence and a reliance on tobacco to cope with stress.     

Structure-activity relationships for euphocharacins A-L, a new series of jatrophane diterpenes, as inhibitors of cancer cell P-glycoprotein

The Mediterranean spurge Euphorbia characias L. afforded twelve new diterpenes based on a jatrophane skeleton named euphocharacins A-L. Their chemical structures were elucidated by extensive nuclear magnetic resonance and mass spectrometry methods. Euphocharacins A-L were tested as inhibitors of the daunomycin-efflux activity of P-glycoprotein from cancer cells. The results were used to extend the structure-activity relationship established for this class of compounds, highlighting the positive effects of propyl and benzoyl groups at positions 3 and 9, respectively, and evidencing the negative effect of a free hydroxyl group at position 2. Among the tested compounds, euphocharacins C and I showed an activity higher than cyclosporin to inhibit Pgp-mediated daunomycin transport.     

The ultrastructure of nasal mucosa in children with asthma

Nasal brushing has sometimes been used to characterize some affections of the respiratory tract, but seldom employed in chronic diseases such as asthma, for the possible presence of cellular inflammation in the small specimens used for electron microscopy. The present study evaluated the ultrastructure of epithelial cells obtained by nasal brushing in 11 allergic children with asthma, before and after staying in an environment free of allergens, usually implicated in the genesis of inflammatory events. The ultrastructural alterations of the nasal mucosa have been graded on the basis of their severity. Grade I lesions were characterized by well-differentiated mucous and ciliated cells. The ciliated cells appeared usually well preserved but decreased in number. In grade II lesions, most of the epithelial surface was covered by mucous cells. A further phenotype composed of poorly differentiated ciliated or mucous cells was detected. Grade III lesions showed aspects of depletion of the ciliated and mucous cells. The epithelium was largely composed of undifferentiated cells. Furthermore, the comparison of specimens at 2 different times of sampling did not differ. The data demonstrate that in allergic children with asthma, the nasal mucosa showed ultrastructural changes, which appeared to be unmodifiable during a prolonged stay in an environment free of allergens. Moreover, the nasal epithelium may provide a convenient sampling site, allowing grade of mucosal damage, with the benefit that the brush method is minimally invasive and avoids complications related to bronchoscopic examination.     

Effects of deferiprone on immune status and cytokine pattern in thalassaemia major

OBJECTIVE: The present study was undertaken to evaluate the possible occurrence of immunological abnormalities in thalassaemia major patients treated with deferiprone (L1). METHODS: Longitudinal observational cohort study. RESULTS: The absolute number of CD8+ lymphocytes was high and the CD4/CD8 ratio low before L1 treatment; these parameters returned to normal after 3 months of L1 treatment. TNF-alpha, IL-2 and IL-2sRalpha were elevated before L1 treatment (11.83 +/- 1.75, 11.75 +/- 3.91, 1,409 +/- 621 pg/ml, respectively), while IL-6 was normal (2.58 +/- 0.79 pg/ml). After 12 months of treatment, IL-10 was higher than in previous periods, although always within the normal range. TNF-alpha, IL-2 and IL-2sRalpha returned to normal after 12, 6, and 3 months of L1 treatment, respectively.