Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.     

The natural history of the double pylorus

A study of 11 patients with "double pylorus" revealed that a second channel between the gastric antrum and the duodenal bulb is the result of ulcer penetration. The fistula can be a sign of spontaneous recovery from ulcerative disease; the fistula occurred in conjunction with clinical improvement in the majority of the patients. The advantages of radiological vs. endoscopic diagnostic procedures are discussed.     

A pragmatic neurological screen for patients with suspected cord compressive myelopathy

Physical therapists commonly use screening tests to identify upper motoneuron lesions such as cord compressive myelopathy (CCM), the presence of which necessitates appropriate medical referral. Signs and symptoms of CCM include sensory and ataxic changes of the lower extremities, poorly coordinated gait, weakness, tetraspasticity, clumsiness, spasticity, hyperreflexia, and primitive reflexes. Clinical tests and measures such as Hoffmann sign, clonus, Lhermitte sign, the grip and release test, the finger escape sign, the Babinski test, and the inverted supinator sign have historically been used as screens for CCM. For effectiveness as a screen, a clinical test or measure should demonstrate high sensitivity. Diagnostic accuracy studies have shown that clinical tests and measures for CCM often display low sensitivity, indicating that a negative finding may falsely suggest the absence of a condition or disease that actually is present. To counter the low levels of sensitivity, screening should include a combination of a thorough patient history, recognition of and appropriate referral for cauda equina symptoms, and clusters of any pertinent contributory tests and measures.     

A Two-Stage Methodology Using K-NN and False-Positive Minimizing ELM for Nominal Data Classification

This paper focuses on the problem of making decisions in the context of nominal data under specific constraints. The underlying goal driving the methodology proposed here is to build a decision-making model capable of classifying as many samples as possible while avoiding false positives at all costs, all within the smallest possible computational time. Under such constraints, one of the best type of model is the cognitive-inspired extreme learning machine (ELM), for the final decision process. A two-stage decision methodology using two types of classifiers, a distance-based one, K-NN, and the cognitive-based one, ELM, provides a fast means of obtaining a classification decision on a sample, keeping false positives as low as possible while classifying as many samples as possible (high coverage). The methodology only has two parameters, which, respectively, set the precision of the distance approximation and the final trade-off between false-positive rate and coverage. Experimental results using a specific dataset provided by F-Secure Corporation show that this methodology provides a rapid decision on new samples, with a direct control over the false positives and thus on the decision capabilities of the model.     

Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis

BACKGROUND: In numerous clinical trials, proton pump inhibitors have demonstrated potent acid suppression and healing of erosive oesophagitis, as well as successful symptom relief for the entire spectrum of gastro-oesophageal reflux disease. AIM: The 'Future of Acid Suppression Therapy' (FAST) trial evaluated, in actual clinical practice, the timing of symptom relief, changes in symptom severity, health-related quality of life and safety in endoscopically confirmed erosive gastro-oesophageal reflux disease treated with rabeprazole. METHODS: This open-label, multicentre study enrolled 2579 patients to receive rabeprazole treatment using 20 mg once daily for 8 weeks. Between two clinical visits (at enrollment and week 8), patients used an interactive voice response system to rate gastro-oesophageal reflux disease symptoms. Subgroup analyses of efficacy were conducted for gender, age, Hetzel-Dent grade, presence of Barrett's oesophagus and for patients reporting previously ineffective symptom relief with omeprazole or lansoprazole. RESULTS: On day 1, rabeprazole significantly decreased daytime and night-time heartburn severity, regurgitation and belching. Complete relief of daytime and night-time heartburn was achieved in 64.0% and 69.2% of symptomatic patients, respectively, on day 1, and in 81.1% and 85.7% of patients, respectively, on day 7. Patients with moderate or severe heartburn symptoms at baseline achieved an even greater degree of satisfactory symptom relief (none or mild) from day 1 onwards. The median time to satisfactory heartburn relief was 2 days. Subgroup analyses showed no consistent differences in efficacy compared to the overall population treated. Health-related quality of life in patients was significantly lower than that of the US general population and improved significantly after 8 weeks of rabeprazole therapy. Rabeprazole was well tolerated, with headache as the most common adverse event, reported by less than 2% of the study population. CONCLUSIONS: In this large, open-label trial, rabeprazole rapidly and effectively relieved gastro-oesophageal reflux disease symptoms in most patients with erosive oesophagitis. Substantial symptom relief was noted on day 1; improvement continued over the first week and at week 4. By week 8, the health-related quality of life had also improved vs. baseline.     

Elevated plasma nociceptin level in patients with Wilson disease

Plasma level of nociceptin, the endogenous agonist of orphanin FQ/ORL1 receptor was found to be significantly elevated in Wilson disease patients (13.98+/-2.44pg/ml, p<0.001, n=20) compared to age-matched healthy controls (9.18+/-1.63pg/ml, n=25). Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutation of the gene ATP7B leading to toxic copper accumulation in the liver and other organs such as brain, kidney and cornea. Measurements were performed by 125I-radioimmunoassay. Neither sex differences nor correlation between plasma nociceptin levels and liver function test results were found. It is suggested that elevated plasma nociceptin level found in Wilson disease patients is due to inhibition of nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N (APN) and endopeptidase 24.15) by the toxic copper deposits in liver and/or brain.     

Histaminergic neurons in the central and peripheral nervous system of gastropods (Helix, Lymnaea): an immunocytochemical, biochemical, and electrophysiological approach

Distribution, chemical-neuroanatomy, concentration, and uptake-release properties of histamine (HA)-containing neurons and the possible physiological effects of HA in the central and peripheral nervous system of the pulmonate snails, Helix pomatia and Lymnaea stagnalis, are described. In the CNS of both species, the distribution pattern of HA-immunoreactive (HA-IR) neurons was similar. In both species the majority were located in the buccal, cerebral, and pedal ganglia. In Helix, approximately 400 HA-IR neurons were seen, whereas in Lymnaea approximately 130 labeled cells were visualized. The neuropils, connectives, commissures, several peripheral nerves, and a part of the peripheral tissues (lip and foot of both species and the upper tentacles of Helix) were innervated by HA-IR elements. Numerous sensory cells were found in the tentacles, lip, and statocysts. The HA concentration values assayed by HPLC ranged from 4.8 to 47.4 pmol/mg in the different central ganglia of Helix, and from 4.3 to 18.6 pmol/mg in Lymnaea CNS, whereas the peripheral tissues contained 0.33-1 pmol/mg HA in Helix and 0.26-0.46 pmol/mg in Lymnaea. In the Lymnaea CNS, a high-affinity (37.6 microM), single component 3H-HA uptake system was demonstrated. 3H-HA release evoked by either electrical stimulation or 100 mM K+ could be prevented in Ca2+-free physiological solution. Voltage-clamp experiments indicated specific changes caused by HA in the membrane conductance of identified central neurons of Helix and Lymnaea. Exogenously applied 10(-5) M HA resulted in the acceleration of locomotion (gliding by foot cilia) of Lymnaea. The findings suggest an important signaling role of HA, described here for the first time, in the nervous system of higher-order, pulmonate, gastropods, involving efferent, integrative, and sensory functions. The data can also be applied as a background for further specification of HA in the regulation of different behaviors in these species.     

Assessment and prevalence of depression in women 45–55 years of age visiting gynecological clinics in Poland

Summary ¶The aims of the Polish survey were to assess efficacy of screening for depression in gynecological practice and to estimate prevalence of depressive disorders in midlife women visiting gynecologists. The study included 2262 female outpatients aged 45–55, who were screened by 120 gynecologists throughout Poland. Patients completed the Becks Depression Inventory (BDI) and were assessed by gynecologists to verify the presence of symptoms of a current Depressive Episode according to ICD-10 diagnostic criteria. Patients who obtained a score of 12 points or more on the BDI were referred for psychiatric evaluation, including the modified version of Mini International Neuropsychiatric Interview (MINI). The study showed that gynecologists in Poland are able to perform screenings for depression effectively in outpatient settings. Results also suggested that about 19% of women aged 45 to 55 years visiting gynecologists may suffer from depressive disorders.Received December 4, 2003; accepted May 9, 2003 Published online July 3, 2003     

Cell type-specific differences in metabolic activation of N-nitrosodiethylamine by human lung cancer cell lines

The metabolism of N-nitrosodiethylamine (NDEA) and its modulation by inhibitors of cytochrome P450 and prostaglandin H synthetase enzymes was investigated in seven well-differentiated early-passage human lung cancer cell lines. NDEA metabolism was assessed by covalent binding and evolution of carbon dioxide. Morphological diagnosis of cell lines was done by light and electron microscopy. Two cell lines (NCI-H69, NCI-H128) with characteristics of small-cell cancer did not metabolize NDEA. Two cells lines (NCI-H322) with features of adenocarcinoma, comprised of Clara cells, and (NCI-H727), with features of pulmonary endocrine cells, were more potent than all other cell lines in metabolizing NDEA. A cell line divided from an adenocarcinoma but comprised of alveolar type-II cells (NCI-H358) metabolized NDEA predominantly via prostaglandin H synthetase. Similarly, several cell lines with features of well-differentiated pulmonary endocrine cells (NCI-H727, NCI-H460) metabolized NDEA via prostaglandin H synthetase, while the cell line comprised of Clara cells (NCI-H322) activated the nitrosamine by cytochrome P450 but not by prostaglandin H synthetase. Although cancer cells may react differently from normal cells to xenobiotics, our data provide substantial evidence for the hypothesis that--as in the hamster--Clara cells and pulmonary endocrine cells are potential major targets of NDEA carcinogenesis in human lung. It is of particular interest that different cell types activate the nitrosamine via different enzyme systems.