Analysis of genetic polymorphisms in acetylcholinesterase as reflected in different populations

Acetylcholinesterase (AChE) plays a crucial physiological role in termination of impulse transmission at cholinergic synapses through rapid hydrolysis of acetylcholine. In addition, it was implicated in amyloid plaque formation, a hallmark of Alzheimer's disease (AD), and most of the drugs used in AD treatment are AChE inhibitors. Thus ACHE is an obvious candidate gene for pharmacogenetic study of AD treatment. However, AChE is a highly conserved molecule, and only a few naturally occurring genetic polymorphisms have been reported in the human gene. The goals of this study were to make a systematic effort to identify natural single nucleotide polymorphisms (SNPs) in the human ACHE gene, and to reveal their population specific architecture. To this end, the genomic coding sequences for AChE of 96 unrelated control individuals from three distinct ethnic groups, African Americans, Ashkenazi Jews and Israeli Arabs, were analyzed. Thirteen ACHE SNPs were identified, ten of which are newly described, and five of which should produce amino-acid substitutions (Arg34Gln, Gly57Arg, Glu344Gly, His353Asn and Pro592Arg). Population frequencies of 11 of the 13 SNPs were established in four different populations, African Americans, Ashkenazi Jews, Sephardic Jews and Israeli Arabs; 17 haplotypes and 5 ethno-specific alleles were identified, and a cladogram of ACHE haplotypes was constructed. Among the SNPs resulting in an amino-acid substitution, three are within the mature protein, mapping on its external surface; they are thus unlikely to affect its catalytic properties, yet could have antigenic consequences or affect putative protein-protein interactions. Furthermore, the newly identified SNPs open the door to a study of the possible association of AChE with deleterious phenotypes - such as adverse drug responses to AChE inhibitors employed in treatment of AD patients and hypersensitivity to pesticides.     

Sleep of preterm neonates under developmental care or regular environmental conditions

Sleep is the main behavioral state of the premature infant. In adult intensive care units, sleep deprivation has been reported as one of the major stressors. Developmental care (DC) aims to decrease stressful events in neonatal intensive care unit and support well-being. AIM: To assess whether DC is accompanied by changes in sleep in preterm neonates. METHODS: A prospective cross-over study included 33 preterm neonates [mean (S.D.): gestational age: 29.3 (1.8) weeks; birth weight: 1245 (336) g]. Polysomnography was performed in two randomly ordered 3-h periods with and without DC. A blinded electrophysiologist analyzed sleep. The total sleep time (TST) was the primary outcome, duration of active (AS), quiet (QS) and indeterminate sleep, and latency before sleep were the secondary outcomes. Non-parametric Wilcoxon tests and ANOVA were used. RESULTS: In DC condition vs. control: TST increased [in minutes, mean (S.E.M.): 156.2 (2.9) vs. 139.2 (4.6), p=0.002], with increase in AS [86.6 (3.7) vs. 77.0 (4.2), p=0.024] and in QS [47.1 (4.1) vs. 36.9 (4.2), p=0.015], and sleeping latency decreased (2.1 (0.7) vs. 10.5 (2.0), p=0.0005]. CONCLUSION: DC promoted sleep in our study. The impact of DC on the neuro-behavioral outcome needs futures studies.     

Factors associated with fragmented sleep at night across early childhood

OBJECTIVE: To identify the factors most strongly associated with sleeping less than 6 consecutive hours at night for children aged 5, 17, and 29 months. DESIGN, SETTING, AND PARTICIPANTS: A randomized survey design used a representative sample of infants born in 1997-1998 in the Canadian province of Quebec. Data were collected by questionnaires and interviews. Interviews were scheduled at home with the mothers. The number of consecutive hours slept at night by 1741 children aged 5, 17, and 29 months was assessed from parental reports. Factors associated with fragmented sleep were investigated for each age in a cross-sectional design. RESULTS: At 5 months of age, 23.5% of children did not sleep 6 consecutive hours. Of the children who did not sleep 6 consecutive hours at night at 5 months or 17 months of age, 32.9% were still not sleeping 6 consecutive hours at night at 29 months of age. The factor most strongly associated with not sleeping at least 6 consecutive hours per night at 5 months of age was feeding the child after an awakening. Parental presence until sleep onset was the factor most strongly associated with not sleeping at least 6 consecutive hours per night at 17 months and 29 months of age. CONCLUSIONS: Sleep consolidation evolves rapidly in early childhood. Parental behaviors at bedtime and in response to a nocturnal awakening are highly associated with the child's sleep consolidation. The effects are probably bidirectional and probably create a long-term problem. Early interventions could possibly break the cycle.     

Drug-associated interstitial lung disease: a diagnostic challenge

Drugs are frequently incriminated as the cause of interstitial pneumonia. There are two major mechanisms of drug-associated interstitial lung disease: direct toxicity and immunoallergic reaction. When a drug is suspected, the difficulty lies in obtaining proof. The chronology of the disease and its manifestations together with earlier evidence reported in the literature can lead to a tentative diagnosis of drug-associated interstitial pneumonia. Proof is obtained through surveillance during the disease course. In nearly all patients, therapeutic decisions must be taken on the basis of suspected drug involvement.     

A role of IL-1 in MPTP-induced changes in striatal dopaminergic and serotoninergic transporter binding: clues from interleukin-1 type I receptor-deficient mice

In mice, the MPTP-induced striatal dopaminergic denervation is followed by a spontaneous partial DAT recovery and by serotoninergic hyperinnervation. We show that IL-1RI-deficient mice have a higher DAT decrease in the ventromedial striatum after MPTP and a higher basal serotoninergic innervation of the whole striatum. These data point to a possible role of IL-1RI in the early MPTP-induced structural or functional remodeling of the nigrostriatal dopamine system.     

Cerebral fat embolism: usefulness of magnetic resonance spectroscopy

We report a case of cerebral fat embolism which occurred in a 33-year-old man after a diaphyseal femoral fracture without cranial traumatism. The initial examination showed an incomplete picture of coma with tetrapyramidal syndrome and cutaneomucous purpura. There was no respiratory damage. We present a magnetic resonance spectroscopy analysis of the cerebral lesions observed in the initial phase of the embolism, as well as follow-up, which has strengthened the clinical and imaging features for the diagnosis.     

Phase-dependent modulation of short latency cutaneous reflexes during walking in man

In reduced animal preparation (cat fictive locomotion) most of our knowledge on the phase-dependent modulation of cutaneous reflexes concerns early- (P1 responses) rather than medium-latency (P2) responses. In contrast, in humans, virtually only P2 responses have been studied because P1 responses are relatively rare in adults. In this work, human P1 and P2 responses following sural nerve stimulation were compared in BF (biceps femoris). Some 14% of all subjects showed P1 responses, which could be either suppressive or facilitatory. The suppressive responses were most common, and they occurred primarily at end swing. When a subject showed both suppressive P1 and P2 responses, the P2 suppressions were stronger than the P1 suppressions (as measured in the same phase at end swing). However, the P2 suppressions were less consistent across subjects than the P1 suppressions. In some subjects, there were also facilitatory P1 responses, mostly throughout stance (when facilitatory P2 responses occur as well). These facilitatory P1 responses were consistent across experimental conditions in these subjects. Similar to the cat, the facilitatory P1 responses were much smaller than the facilitatory P2 responses. It is concluded that P1 and P2 reflexes can appear independently from each other, but that their modulation in the step cycle is mostly quite similar in some phases of the step cycle (end swing).     

First prospective study of the recognition process of melanoma in dermatological practice

BACKGROUND: Early detection is crucial to improve melanoma prognosis. Different diagnostic guides such as the ABCD rule (asymmetry [A], irregularity of borders [B], unevenness of distribution of color [C], and diameter [D]) have been proposed to identify melanoma, but their efficacy in real life is questionable. We investigated the recognition process of melanoma by dermatologists to use as a model to improve self-detection in the general population and to train students and general practitioners. OBJECTIVES: To understand the major principles of the recognition process of nevi and melanoma unconsciously used by dermatologists. DESIGN: Prospective survey recording the immediate perceptions of dermatologists of the morphologic features of the lesion and intuitive diagnostic opinion about 4036 consecutive resected nevi and melanoma. SETTING: One hundred thirty-five volunteer dermatologists in their daily practices. MAIN OUTCOME MEASURES: Perceptions of the image best explaining the diagnostic opinion and best predicting the final diagnosis by univariate and multivariate analysis. RESULTS: The immediate diagnostic opinion of the dermatologist is mainly explained by an unconscious reference to the overall pattern compared with the common nevi, but also compared with the other nevi of the individual (the "ugly duckling sign"). The dermatologist's ability to discriminate between nevi and melanoma relies on the assessment of the overall pattern, the ugly duckling sign, and the knowledge of a recent change. A separate or combined analysis of individual morphologic criteria such as ABCD does not seem to play a major role in this recognition process. CONCLUSIONS: Persons most skilled at the clinical detection of melanoma seem to unconsciously rely on cognitive (overall pattern) and comparative (ugly duckling sign) processes rather than an algorithm of morphologic criteria (ABCD). These concepts could be tested in the medical training of general practitioners and education of the general population, where they might be more efficient than algorithms such as the ABCD criteria.