The incidence and natural history of Raynaud's phenomenon in the community

OBJECTIVE: Raynaud's phenomenon (RP) is a common disorder, yet its incidence and natural history are unknown. Our objective was to determine the incidence and natural history of RP not associated with a connective tissue disease in a large, community-based population. METHODS: Using serial examinations of the Framingham Heart Study offspring cohort, we collected data regarding RP symptoms for 717 women and 641 men over a 7-year period. We used validated criteria for RP classification and categorized participants as having incident, persistent, or remitted RP. We performed sex-specific analyses of RP status by age, body mass index, vibratory tool use, season of examination, state of residence, use of antihypertensive medications, and smoking status. RESULTS: The mean +/- SD age of participants was 53.5 +/- 10 years. The incidence of RP was 2.2% in women (n = 14) and 1.5% in men (n = 9). Of the 78 women and 50 men who had RP at baseline, 36% of women (n = 28) and 36% of men (n = 18) had persistent RP. RP remitted in 64% of women (n = 50) and 64% of men (n = 32), with 41 women and 25 men meeting no or only 1 RP criterion at followup. RP episodes were infrequent and rarely interfered with daily activities. CONCLUSION: This is the first prospective study to determine the incidence and natural history of RP in a community-based cohort. Our data demonstrate that RP not associated with a connective tissue disease is frequently a transient phenomenon and rarely interferes with daily activities.     

Rat nicastrin gene: cDNA isolation, mRNA variants and expression pattern analysis

Nicastrin is a type 1 transmembrane glycoprotein that interacts with presenilin, Aph-1, and Pen-2 proteins to form a high molecular complex with gamma secretase activity. Then, nicastrin has a central role in presenilin-mediated processing of beta-amyloid precursor protein and in some aspects of Notch/glp-1 signaling in vivo. Here, we isolated a rat nicastrin cDNA and investigated gene expression in embryonic and adult rat tissues. The predicted amino acid sequence is comprised of 708 residues and showed a high degree of identity with other vertebrate orthologs. Besides full-length nicastrin mRNA, we identified an alternative spliced variant lacking the whole exon 3 and predicted to encode a 62-residue-long truncated protein. Full-length nicastrin mRNA was observed to be ubiquitously expressed, while the spliced variant was preferentially transcribed in the nervous system, whether in embryonic or adult neural tissues. Studies performed on primary cell cultures demonstrated that the short isoform was expressed in neurons, but not in astrocyte and microglial cells. Further experiments performed to verify the presence of the variant in neuroblastoma culture failed to show any truncated protein. Treatments by cyclohexamide showed the involvement of a quality control-based surveillance mechanism, which selectively degrades the exon 3-skipped isoform. In summary, this is the first report describing a novel skipped isoform of nicastrin which may suggest a new possible control mechanism based on the alternative splicing and nonsense-mediated mRNA decay to regulate brain protein expression and provide newer insights into potential implication in Alzheimer's disease.     

Lack of inhibition in Parkinson's disease: evidence from a lexical decision task

Persons affected by Parkinson's disease (PD) often show an increased semantic priming effect from target words in lexical decision tasks (hyper-priming) as compared to age-matched controls. In this study, a lexical decision task was used to investigate both semantic priming (Experiment 1) and repetition priming (Experiment 2) from distractor words in PD patients and age-matched controls. With this negative priming procedure, target words in successive trials are never related, and therefore participants always have to switch between unrelated target words. Instead, it is the distractor prime word that is either related or unrelated to the subsequent target, giving the measure of priming. Results showed that PD patients demonstrated a robust effect of positive semantic priming from distractor words. Participants from the control group did not show any semantic priming effect (positive or negative) from distractors. Similarly, PD patients showed positive repetition priming from distractor words, but the control group showed significant repetition negative priming. These results support the view that the hyper-priming effect typically shown by persons with Parkinson's disease is the result of impaired inhibitory processes required to control word activation during reading.     

Effects of an antibiotic cycling program on antibiotic prescribing practices in an intensive care unit

Various interventions have been proposed to combat the increase of antibiotic resistance and influence antibiotic prescribing practices. A prospective cohort study in a medical intensive care unit was conducted to determine the effect of an antibiotic cycling program on patterns of antibiotic use and to determine patient factors associated with cycling adherence. Four major classes of antibiotics for empirical therapy of suspected gram-negative bacterial infections were rotated at 3- and 4-month intervals. During the study, 1,003 patients received antibiotic therapy with at least one of the study drugs; of the 792 receiving cycle antibiotics during the cycling period, 598 (75.5%) received an on-cycle drug. Compared to the baseline, cycling recommendations increased the use of the target cycle agent: the use of cephalosporins increased during cycle 1 (56 to 64% of total antibiotic days, P < 0.001), fluoroquinolone use increased in cycle 2 (24 to 55%, P < 0.001), carbapenem use increased during cycle 3 (14 to 38%, P < 0.001), and use of extended-spectrum penicillins increased in cycle 4 (5 to 36%, P < 0.001). Overall, 48% of total cycle antibiotic days were compliant with the cycling protocol. On average, 8.8 days per patient were spent receiving on-cycle drugs (range, 1 to 109). Cycle periods that specified carbapenem and fluoroquinolone use had the highest number of off-cycle days (62 and 64%). Predictors of on-cycle antibiotic use were increased severity of illness, as measured by an acute physiology and chronic health evaluation II score, and greater length of intensive care unit stay. In conclusion, the successful implementation of this cycling protocol increased antibiotic heterogeneity over time in the study unit.     

Features of pregnant women with diabetes mellitus

It is about a quantitative study aimed at knowing the features of 105 pregnant women attended at Hospital de Clínicas de Porto Alegre, Brazil, from January 2000 to January 2001. The results allowed the analysis of the delivery as well as baby conditions in addition to the values of the glycemia profile during the gestation. Moreover, they supplied information regarding the completion of the gestations of diabetic women that have made their pre-natal care at the hospital. These results provide significant input for the health team that attend this group of pregnant women and safety for the team performance and, as a result, for the pregnant women.     

Effects of a 20-HETE antagonist and agonists on cerebral vascular tone

This study examined the effects of a 20-hydroxyeicosatetraenoic acid (20-HETE) antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (WIT002) and two agonists, 4-amino-N-(20-hydroxy-eicosa-5(Z),14(Z)-dienoyl) benzenesulfonamide (ABSA) and 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (WIT003), on the diameter of rat middle cerebral arteries in vitro and on cerebral blood flow in vivo. WIT003, ABSA and 20-HETE all had a similar effect to reduce the diameter of the middle cerebral artery by 26%. WIT003 and 20-HETE both increased intracellular Ca2+ concentration ([Ca2+]i) in vascular smooth muscle cells isolated from the middle cerebral artery. In contrast, WIT002 had no effect on the basal diameter of the middle cerebral artery but it attenuated the vasoconstrictor responses and the rise in [Ca2+]i in vascular smooth muscle cells following administration of 20-HETE and 5-hydroxytryptamine (5-HT). WIT003 partially restored the vasoconstrictor response to 5-HT in the middle cerebral artery after administration of an inhibitor of the endogenous synthesis of 20-HETE. Infusion of the 20-HETE agonists, WIT003 and ABSA, into cisterna magna of rats reduced baseline cerebral blood flow by 20%, whereas administration of the 20-HETE antagonist, WIT002, had no effect. Intracisternal injection of WIT002 attenuated the fall in cerebral blood flow following injection of blood into the cisterna magna, whereas administration of the 20-HETE agonist, ABSA, potentiated this response. These findings indicate that the 20-HETE agonists, WIT003 and ABSA, increase cerebral vascular tone both in vivo and in vitro and suggest blocking the vasoconstrictor actions of 20-HETE may be useful to prevent the acute fall in cerebral blood flow following subarachnoid hemorrhage.     

Autoimmunization induced by interferon alpha therapy in chronic hepatitis C

We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough.     

Screening for eating disorders and high-risk behavior: caution

OBJECTIVE: The current study reviews the state of eating disorder screens. METHODS: Screens were classified by their purported screening function: identification of cases with (a) anorexia nervosa only; (b) bulimia nervosa only; (c) eating disorders in general; (d) partial syndrome, eating disorder not otherwise specified (EDNOS), or subclinical; (e) not a-d but at high risk. Information is presented on development, psychometric properties, and external validation (e.g., sensitivity, specificity, positive predictive values, and negative predictive values). RESULTS: Screens differ widely with regard to objective, psychometric properties and the validation methodology used. Most screens that identify cases are not appropriate for the identification of at-risk behaviors. Little data on the external validity of screens are available. DISCUSSION: Screens should be used with caution. A sequential procedure, in which subjects identified as being at risk during the first stage is followed by more specific diagnostic tests during the second stage, might overcome some of the limitations of the one-stage screening approach.     

No association between the lipoprotein lipase S447X polymorphism and Alzheimer's disease

Results from various genetic association studies of the lipoprotein lipase (LPL) S447X polymorphism and Alzheimer's disease (AD), range from a statistically significant negative association of clinically examined patients to a non-significant but consistent trend for under-representation of the X447 allele in neuropathologically confirmed subjects. In this report we have compared the distribution of the above polymorphism in an independent group of clinically diagnosed AD patients, including a subgroup where the disease was pathologically confirmed, and a spousal control group. No statistically significant differences emerged from this comparison. We conclude that LPL cannot be a major factor in pathogenesis of AD.