Health care providers' awareness on medical management of children with autism spectrum disorder: cross-sectional study in Russia.

BACKGROUND: Autism spectrum disorder (ASD) is a complex developmental range of conditions that involves difficulties with social interaction and restricted/repetitive behaviors. Unfortunately, health care providers often experience difficulties in diagnosis and management of individuals with ASD, and may have no knowledge about possible ways to overcome barriers in ASD patient interactions in healthcare settings. At the same time, the provision of appropriate medical services can have positive effects on habilitative progress, functional outcome, life expectancy and quality of life for individuals with ASD. METHODS: This online survey research study evaluated the awareness and experience of students/residents (n = 247) and physicians (n = 100) in the medical management of children with ASD. It also gathered the views and experiences of caregivers to children with ASD (n = 158), all based in Russia. RESULTS: We have established that the Russian medical community has limited ASD knowledge among providers, and have suggested possible reasons for this. Based on results from online surveys completed by students/residents, non-psychiatric physicians, and caregivers of children diagnosed with ASD, the main problems pertaining to medical management of individuals with ASD were identified. Possible problem solving solutions within medical practice were proposed. CONCLUSIONS: The results from this study should be considered when implementing measures to improve healthcare practices, and when developing models for effective medical management, due to start not only in Russia but also in a number of other countries.

Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons.

BACKGROUND: Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled. METHODS: Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors. KEY RESULTS: Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC-030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Conversely, the serotonin1-4, histamine1-3, tachykinin1-3 receptor blockade, and serine protease inhibition had no significant effect. CONCLUSIONS & INFERENCES: Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS.

The beta3-adrenoceptor agonist SR58611A ameliorates experimental colitis in rats.

Beta(3)-adrenoceptor agonists protect against experimental gastric ulcers. We investigated the effects of the beta(3)-adrenoceptor agonist SR58611A on 2,4-dinitrobenzene sulphonic acid-induced colitis in rats and analysed the expression of beta(3)-adrenoceptors in the colonic wall. SR58611A was administered orally (1-10 mg kg(-1)) for 7 days, starting the day before induction of colitis. Colitis was assessed by macroscopic and histological scores, tissue myeloperoxidase activity, interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels. Reverse transcription-polymerase chain reaction and immunohistochemical analysis were used to examine the expression of beta(3)-adrenoceptors. SR58611A significantly reduced the severity of colitis as well as the tissue levels of TNF-alpha, IL-1beta and IL-6. Colitis was associated with a decreased expression of beta(3)-adrenoceptor mRNA in the mucosal/submucosal layer of distal colon and this reduction was not affected by SR58611A. Immunohistochemical analysis revealed beta(3)-adrenoceptors within the muscularis externa, in myenteric neurons and nerve fibres and in the submucosa. beta(3)-Adrenoceptor immunoreactivity was decreased in inflamed tissues compared to controls, particularly in the myenteric plexus; this reduction was counteracted by SR58611A. Amelioration of experimental colitis by the selective beta(3)-adrenoceptor agonist SR58611A suggests that beta(3)-adrenoceptors may represent a therapeutic target in gut inflammation.

Review article: the pharmacological treatment of acute colonic pseudo-obstruction.

Acute colonic pseudo-obstruction (Ogilvie's syndrome) can be defined as a clinical condition with symptoms, signs and radiological appearance of acute large bowel obstruction unrelated to any mechanical cause. Recent reports of the efficacy of cholinesterase inhibitors in relieving acute colonic pseudo-obstruction have fuelled interest in the pharmacological treatment of this condition. The aim of the present review is to outline current perspectives in the pharmacological treatment of patients with acute colonic pseudo-obstruction. The best documented pharmacological treatment of Ogilvie's syndrome is intravenous neostigmine (2-2.5 mg), which leads to quick decompression in a significant proportion of patients after a single infusion. However, the search for new colokinetic agents for the treatment of lower gut motor disorders has made available a number of drugs that may also be therapeutic options for Ogilvie's syndrome. Among these agents, the potential of 5-hydroxytryptamine-4 receptor agonists and motilin receptor agonists is discussed.

Gene-gene interaction in the RAS system in the predisposition to myocardial infarction in elder population of St. Petersburg (Russia).

The aim of this study was to estimate the frequencies of some DNA polymorphisms of two genes of the renin-angiotensin system (RAS), M235T angiotensinogen gene and insertion-deletion polymorphism in angiotensin-converting enzyme gene, in older (>55 years old) myocardial infarction survival and control groups. For this purpose 198 myocardial infarction (MI) patients and 152 randomly selected healthy persons have been analyzed. We have not found any differences in allele and genotype distribution in the above-mentioned genes for either group. However, statistical research showed a significant increase of double homozygotes IITT in the group of MI patients as compared with those in the control group. In this respect we suggested that gene-gene interaction in the RAS system may be considered to be a predisposing factor for MI development.

Age as a risk factor for myocardial infarction in Leiden mutation carriers.

A single factor V gene G-A mutation (Arg506Gln) underlying activated protein C (APC) resistance is a common risk factor for venous thromboembolism. It is still unclear whether the factor V Leiden predisposes patients to arterial thrombosis and myocardial infarction (MI). To determine a correlation between the factor V Leiden mutation and MI in different age categories, DNA samples from 287 patients with "early" and "late" MI were investigated. As control groups 373 young subjects (mean age 11 years) and 110 elderly ones (mean age 80 years) were studied. We found a significant difference in mutant allele distribution in the "late" MI group compared to the "early" MI group (chi2 = 9.86, OR = 13,7, P < 0.005) and the control group of elderly subjects (chi2 = 5.92, OR = 8.6, P < 0.02). The mean age of MI patients carrying the Leiden mutation was 72 years, i.e., 12 years higher than the mean age of all investigated MI patients (60 years). Thus, we found a statistically significant correlation between MI and factor V Leiden mutation in elderly subjects.

Comparative analysis of apo(a) gene alleles: distribution of pentanucleotide repeats in position -1373 and C/T transition in position +93 among patients with myocardial infarction and a control group in St. Petersburg, Russia.

To evaluate whether polymorphisms in the 5' region of the apolipoprotein(a) gene alter the risk for myocardial infarction, 289 Russian male patients with myocardial infarction (MI) and 284 subjects in a control group were investigated regarding the distribution of pentanucleotide repeats (PNRs) at position -1373 and a C/T transition at position +93. For detection of the C/T (+93) allele, we developed a rapid, nonisotopic method by mismatch PCR-mediated site-directed mutagenesis and restriction enzyme digestion. We observed significant differences in prevailing alleles with over eight (TTTTA) repeats among MI patients, including those with MI younger than 55 years of age. We observed the prevalence of the T (+93) allele in children without a family history of CHD compared to young MI patients. These findings support the notion that PNR alleles with over eight (TTTTA) repeats may play a pathogenic role, and the T (+93) allele may have a protective effect for the inherited predisposition to heart disease.

[DNA polymorphism in the region of APOB100, APOCIII, APOE, and angiotensin-converting enzyme genes and indicators of the lipid spectrum in children and adolescents in St. Petersburg]. / Polimorfizm DNK v oblasti genov APOB100, APOCIII, APOE, angiotenzin- konvertiruiushchego fermenta i pokazateli lipidnogo spektra u detei i podrostkov Sankt-Peterburga.

Polymorphisms of 3 apolipoprotein genes Xba I apoB, Sstl apoCIII, and apoE and the insertion-deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and lipid levels were studied in a random sample of 403 children and adolescents aged 6 to 18 years living in St. Petersburg. The children were divided in 4 age groups with consideration for the relative body weight index: group 1.6 to 9 years; II, 10-12; III, 13-15; and IV, 16-18 years. The first three groups were divided by sex, the fourth was not because it was the smallest. Relationships between lipid levels and DNA polymorphisms of the above genes were analyzed in all groups. Effects of apoB Xbal, apoCIII Sstl, apoE, and ACE genotypes on the levels of the blood basic lipids were analyzed using Statgraphics software. A marked effect of the apoE (E3/E4) genotype on the total and LDL-cholesterol variability was observed in group IV. The individuals carrying the E4 apoE allele had increased levels of total and LDL-cholesterol (p < 0.02 and p < 0.03, respectively). The level of triglycerides was higher in the subjects carrying the S2 apoCIII allele in the third group (p < 0.04). A statistically reliable difference was however observed only in girls (p < 0.01). We failed to detect reliable correlations between lipid levels and various apoB and ACE genotypes. Hence, the genetic variants of apoCIII and apoE genes affect the blood lipid levels as early as in adolescence.

[Leukinferon in the treatment of patients with acute viral hepatitis b]. / Primenenie leikinferona v lechenii bolnykh ostrym virusnym gepatitom B.

Leukinferon activity was studied in a controlled trial including 30 patients with acute viral hepatitis. The disease ran a moderate severity course in the majority of the patients. Leukinferon, a combined preparation of natural interferon and cytokines produced by virus-induced leukocytes, has marked immunomodulating properties at moderate antiviral activity. Leukinferon was administered intramuscularly for 10 days according to the following scheme: day 1-1 sample 3 times, day 2-1 ampule 2 times, day 3-10-1 ampule a day (overall 1 x 10(5) U of interferon). Due to leukinferon the symptoms of intoxication declined, hepatic biochemistry normalized more rapidly as well as the period of viremia and antigenemia. Positive clinical trends correlated with interferon system improvement and activation of natural killers. 6 months later complete recovery was registered in all leukinferon-treated subjects.