[Open, non-comparative phase III clinical study to evaluate the efficacy and safety of sapropterin in patients with phenylketonuria and hyperphenylalaninemia].

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inherited disease associated with impaired metabolism of the amino acids phenylalanine (Phe) and tyrosine. The main criterion for diagnosis of PKU is high blood Phe level determined during neonatal screening. In case where PKU patient is responsive to tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe metabolism and thereby enhancing patient tolerance to natural products. AIM: The present open, non-comparative clinical study was initiated to assess the degree and frequency of response after 8-day sapropterin administration and assess the safety of 6-week sapropterin treatment in patients with PKU and hyperphenylalaninemia. PATIENTS AND METHODS: The study enrolled 90 patients with PKU. The criterion of response to 8-day sapropterin therapy was the reduction of Phe blood levels ≥ 30% compared with the baseline value. RESULTS: Positive response to treatment was observed in 30 (33.3%) patients (95% CI 23.7-44.1). The mean percentage change in Phe blood levels after the 8-day response test period compared to Phe levels prior to dosing was 14.1 ± 28.4% in the overall subject population (95% CI 8.2-20.1) and 44.3 ± 15.1% in the subpopulation of patients with a positive response (95% CI 38.6-49.9). During the study, adverse events were reported in 24 (26.7%) patients in the overall population in 16 (53.3%) patients in the subpopulation who had a response. CONCLUSION: The study results confirmed the efficacy and safety of sapropterin therapy in patients with PKU, which is consistent with international clinical trials data.

[The influence of genetic factors on the effectiveness of eradication therapy of Helicobacter pylori infection in children].

Efficacy of sequential eradication therapy for H. pylori was studied in 176 adolescents (mean age 14.3 years) with different PPI metabolism types. Group I consisted from the patients received omeprazole as PPI in combined treatment with amoxycilline, clarithromycine and tinidazole, Group II--patients treated with rabeprazole in the combination with the same antibacterial drugs. In all the patients, CYP2C19 genotype was identified as a control rate of PPI metabolism (extensive, intermediate and poor metabolizers). Sequential therapy in the children with intermediate and poor metabolic activity demonstrated a high eradication rate irrespective of PPI type (> 80%). In the patients with extensive metabolism taking omeprazole, eradication standard turned out to be lower (63.4%) than in the rabeprazole group (82.3%) (p = 0.026). Results of our survey confirmed a potential advantage of rabeprazole-based treatment compared with omeprazole-containing regimen in the sequential treatment of H. pylori infection in childhood.

[Rifaximin in combined treatment of the Helicobacter pylori infection in childhood].

AIM: To provide a pilot study of empiric rifaximin, bismuth subcitrate, furazolidone/nifuratel triple therapy for H. pylori gastritis in childhood. MATERIALS AND METHODS: Forty one pediatric outpatients (27 females, mean age 14.5 +/- 1.4 ys) with H. pylori-associated chronic gastritis who underwent endoscopy for dyspeptic symptoms received the combination of bismuth subcitrate (8/mg/kg/day, q. d. s.) for 14 days, rifaximin (800 mg/day) for 10 days and furazolidone (10 mg/kg/day, q. d. s.) or nifuratel (15 mg/kg/two times daily) for 10 days. H. pylori status was determined before the treatment by modified Giemsa staining/urease test and after the treatment (in 4-6 weeks) by ammonia breath test. RESULTS: H. pylori was eradicated in 35 children (85.4%; 95% CI: 75.4-96.4 ITT and PP tests). There were no serious adverse reactions and were no withdrawals due to any side effects. CONCLUSION: The combination of rifaximin, bismuth subcitrate and furazolidone/nifuratel was an effective and tolerable regimen for initial H. pylori eradication.

[Immune polymorphism analysis of HLA class II antigens in ulcer diseases associated with Helicobacter pylori in children].

UNLABELLED: Previous investigations have linked specific HLA class II alleles DRB1 and DQB1 to H. pylori infection (Y. Huang et al., 2005). AIM: to investigate potential contribution of HLA-DRB1 and DQB1 alleles in H. pylori infection susceptibility in a Russian pediatric population. METHODS: Polymerase chain reaction-sequence specific primer (PCR-SSP) method was used to study the HLA-DRB1, DQB1 allelic frequency distribution in 162 children (93 female) with H. pylori infection was determined by culture, breath test and histology. RESULTS: The carrier frequency of DQB1*03 was higher among H. pylori--positive patients with chronic gastritis only compared with H. pylori-negative patients. The difference in carrier frequencies for HLA-DRB1*17 was higher in H. pylori-positive ulcer patients compared with an uninfected controls (chi2 = 3.69, p = 0.027). In addition, the frequency of genotypes that possess HLA-DQB1*07 allele in the H. pylori-positive children (with peptic ulcer/ chronic gastritis only) was significantly lower than that in the H. pylori-negative control group. CONCLUSIONS: HLA-DQB1*07 allele may be associated with protection against H. pylori infection independently of clinical outcome. At the same time, HLA-DRB1*17 allele might be associated with susceptible gene to peptic ulcer formation among H. pylori-positive children.

[Rifaksimin in complex treatment of Helicobacter pylori infection in children (a pilot study)].

AIM: To provide a pilot study of empiric rifaximin, bismuth subcitrate, furazolidone/nifuratel triple therapy for H. pylori gastritis in childhood. MATERIALS AND METHODS: Forty one pediatric outpatients (27 females, mean age 14.5+/-1.4 ys) with H. pylori-associated chronic gastritis who underwent endoscopy for dyspeptic symptoms received the combination of bismuth subcitrate (8 mg/kg/day, q. d. s.) for 14 days, rifaximin (800 mg/day) for 10 days and furazolidone (10 mg/kg/day, q. d. s.) or nifuratel (15 mg/kg/two times daily) for 10 days. H. pylori status was determined before the treatment by modified Giemsa staining/urease test and after the treatment (in 4-6 weeks) by ammonia breath test. RESULTS: H. pylori was eradicated in 35 children (85.4%; 95%CI: 75.4-96.4 ITT and PP tests). There were no serious adverse reactions and were no withdrawals due to any side effects. CONCLUSION: The combination of rifaximin, bismuth subcitrate and furazolidone/nifuratel was an effective and tolerable regimen for initial H. pylori eradication.

[Urine chemiluminescence in preclinical diagnosis of neonatal drug-induced nephropathy]. / Khemiliuminestsentsiia mochi v doklinicheskoi diagnostike neonatal'nykh lekarstvennykh nefropatii.

Animal experiments demonstrate that gentamycin, kanamycin and carbenicillin affect lipid peroxidation in the kidneys. This can be registered by chemiluminescence of renal and urinary homogenates. This phenomenon was also used in functional examination of the kidneys in 161 neonates treated by antibiotics. The earliest renal dysfunctions due to nephrotoxicity were detected by chemoluminescence induced by ions of bivalent iron. The method is simple and rapid, this making it convenient in neonatal practice for detection of nephropathy before the symptoms presentation.

[A cytochemical study of the blood cells in the newborn]. / Tsitokhimicheskie issledovaniia kletok krovi novorozhdennykh.

The cytochemical parameters (acid and alkaline phosphatases, peroxidase, and glycogen) of the peripheral blood leukocytes were studied in 58 clinically full-term newborns delivered by cesarean section and in 22 healthy newborns delivered spontaneously. Statistically significant deviations of a number of blood biochemical characteristics were detected in the newborns delivered by cesarean section in the course of the early neonatal period (on days 1, 5, 10 of life), this pointing to endogenously predetermined instability of the body of the risk-group babies. The authors regard the cytochemical analysis of the blood cells as a highly sensitive method for the detection of disordered adaptation of the newborns.

[Adaptation of the circulatory system of newborn infants with intrauterine hypotrophy]. / Adaptatsiia sistemy krovoobrashcheniia novorozhdennykh s vnutriutrobnoi gipotrofiei.

A study was made of adaptation of the circulatory system in 40 full-term newborns with grade II and III intrauterine++ hypotrophy during the early neonatal period. Analysis of the hemodynamics demonstrated the study group children to have arterial hypertension, BP lability, and high peripheral vascular resistance. The conclusion has been made about the necessity of classifying intrauterine hypotrophy newborns with the group at risk for adaptation failure in the circulatory system.