EFFICACY OF THE ALGORITHMIC STEP-UP APPROACH OF INTERVENTIONAL TREATMENT OF PATIENTS WITH ACUTE NECROTIZING PANCREATITIS.

Aim - to estimate the efficacy of the algorithmic step-up approach of interventional treatment of acute necrotizing pancreatitis (ANP).; We performed a prospective observational cohort study of the efficacy of the developed approach of surgical treatment of 317 patients with different morphological forms of ANP. The following parameters were collected for each episode: length of hospital stay, mortality rate, occurrence of organ failure and local complications.; Transcutaneous punction/drainages were applied as the first step in 37 patients with acute necrotic collections. In the presence of walled-off pancreatic necrosis (WOPN) endoscopic procedures were preferred in case their close localization to the stomach or duodenum in 65 observations. Initial surgical treatment was not effective in 18.8% and video-assisted retroperitoneal debridement in patients with ANP or necrosectomies under endoscopic control in cases of WOPN were performed. Involuntary laparotomic necrosectomies were conducted in 14.5% of patients as a final step of the suggested algorithmic approach. During postoperative period complications occurred in 28.3% of patients. They included 7 new episodes of organ failure, 4 cases of arosive hemorrhage, and 5 cases of pancreatic and duodenal fistulas. Overall mortality rate was 3.3%, after laparotomic surgical treatment - 6.5%.; Surgical treatment in patients with ANP based on the developed algorithmic step-up approach is followed by acceptable complication and mortality level.

[EXPERIMENTAL PHARMACOKINETICS AND PHARMACODYNAMICS OF GB-115 DIPEPTIDE ANXIOLYTIC SUBSTANCES].

Pharmacokinetics and pharmacological activity of GB-115 dipeptide anxiolytic after oral administration in the form of crystalline and micronized substances was studied in albino male rats. In contrast to crystalline, the micronized substance exhibited better pharmacokinetic parameters and higher bioavailability. In the "elevated plus maze" test, GB-115 in micronized form at a dose 0.3 mg/kg demonstrated pronounced anxiolytic properties during prolonged period as compared to crystalline substance at the same dose. The obtained data allow the micronized substance of GB-115 to be recommended for inclusion in pharmaceutical composition of new dipeptide anxiolytic drug formulations.

[Specific features in pharmacokinetics of the original neuroleptic dilept in animals and humans].

Interspecies differences in pharmacokinetics of the original neuroleptic drug dilept have been studied in experimental animals (rabbits and rats) and volunteers after single oral administration of tablets and tablet mass of the drug. Parent drug in the rabbit blood plasma was detected for 4 h, in the rat plasma for about 2 h, and in the human blood plasma for about 1 h after drug administration. The degrees of dilept biotransformation into metabolites (defined as metabolism intensity, AUCM/AUCP) in rats were 21.3 (for M-1) and 1645 (for M-2), in human volunteers - 5.8 and 658.5, and in rabbits - 1.6 and 125.8, respectively. Thus, the intensity of drug metabolism in experimental animals and volunteers was different and decreased in the series rats humans rabbits.

[Pharmacokinetics of three peroral dosage forms of new dipeptide anxiolytic drug GB-115].

Comparative analysis of the pharmacokinetics and bioequivalence of a new dipeptide anxiolytic compound GB-115 in three drug forms for peroral administration, developed in the experimental technology department of the Institute of pharmacology RAMS, was carried out. Three drug forms of GB-115 and a micronized substance of this compound were different in composition and technology of production. As a result of the investigations of GB-115 pharmacokinetics, drug form No. 2 (with a relative bioequivalence of 192%) showed advantages in comparison to the micronized parent substance and two other drug forms (bioequivalence, 53 and 117%) and can be recommended for further pharmacological studies.

[Surgical treatment and prophylaxis of pulmonary thromboembolism for renal cancer with presence of the implantation clots of the inferior vena cava].

Surgical treatment of 91 patients, suffering the renal cell cancer (RCC), complicated by tumoral thrombosis of inferior vena cava, was analyzed. In accordance to the Mayo clinic classification, there in the patients the tumoral thrombus spreading was revealed, depending on tumoral affection of a kidney (right-sided/left-sided): level 0--in 39 (31/8); level I--in 20 (6/14); level II--in 17(12/5); level III--in 11 (11/0); level IV--in 4 (3/1). Incomplete apparatus cavaplication was performed in 32 patients. There was proved, that incomplete apparatus cavaplication constitutes an effective method of surgical prophylaxis of pulmonary thromboembolism in patients, suffering RCC.

[Clinic pharmacokinetics of a new original antipsychotic drug Dilept].

The pharmacokinetic study of a new original antipsychotic drug Dilept in healthy volunteers was performed. Volunteers received Dilept as single 20, 40 or 60 mg tablets. The parent drug in the human blood plasma was detected in low concentrations and short-term time due to intensive biotransformation with formation of two metabolites N-caproyl-L-prolyl-tyrosin (M-1) and N-caproyl-L-prolin (M-2). After 20 and 40 mg of Dilept parent drug was detected in certain time points and after 60 mg for 1 h. M-1 and M-2 metabolites were registered in the blood plasma for 4 - 8 h. Theirs concentrations were 10 - 100 times higher of unchanged drug ones. Metabolites pharmacokinetics in the studied dosage range was nonlinear.

[Radical nephrectomy and thrombectomy in patients with renal cell cancer complicated by tumoral thrombosis of the renal vein and vena cava inferior].

Surgical treatment was conducted in 81 patients, suffering renocellular cancer (RCC), complicated by a renal vein and vena cava inferior thrombosis. According to the Mayo clinic classification, the level of a tumoral thrombus spread was established: the 0 level--in 37 patients, the level I--in 19, the level II--in 17, the level III --in 6, and the level IV--in 2. There were substantiated the optimal surgical accesses and technique of radical nephrectomy and thrombectomy for RCC, complicated by a renal vein and vena cava inferior thrombosis. It is recommended to apply transabdominal accesses: the extended median laparotomic, bilateral subcostal of a "Chevron" or "Mercedes" type. There was shown, that the access choice depends on the level of the tumoral thrombus localization.

[Polymorphism of endocellular isoenzymes Schizophyllum commune Fr. (Basidiomycetes) in territory of Donetsk area].

Results of research of endocellular isoenzyme polymorphism of Schizophyllum commune Fr. cultures growing on the territory of Donetsk region are presented. Description of AMY, ADH, GPDH, GDH, SDH, EST electrophoretic spectrum has been carried out. The enzyme systems ADH, GPDH and GDH were monomorphic. The greatest variety of endocellular isoforms was shown for EST. Well defined six zones were detected and for three of them the polymorphism was peculiar.

Regional and subcellular localization of cycloprolylglycine in rat brain.

HPLC analysis showed that endogenous cyclopeptide cycloprolylglycine exhibiting mnemotropic and anxiolytic properties is nonuniformly distributed between brain structures in rats: its contents in the whole brain, cortex, and hippocampus were 29.2±1.6, 38.9±8.0, 126.4±32.4 nmol/g, respectively. Cycloprolylglycine distribution between subcellular fractions of brain neurons is also nonuniform: 60% cyclopeptide appeared in the nuclear fraction.

[Experimental pharmacokinetics of the new neurotensine-derived antipsychotic drug dilept].

The metabolism and pharmacokinetics of a new neurotensine-derived dipeptide drug dilept (N-caproyl-L-prolyltyrosine methyl ester) and its tentative metabolites after intravenous and peroral administration of the parent drug and its tabletized form in rats have been studied by HPLC-ESI(-)-MS/MS method. It is established that unchanged dilept (detected in the blood plasma for no less than 30 min) as well as N-caproyl-L-proline and N-caproyl-L-prolyl-L-tyrosine (both detected in the blood over more than 4 h) are the major metabolites in the bloodstream upon peroral administration of the drug. The proposed structures of metabolites were confirmed by countersynthesis. Dilept and N-caproyl-L-prolyl-L-tyrosine penetrate through the blood - brain barrier. The drug is rapidly absorbed, distributed, and metabolized in the rat organism. Peroral administration of dilept in rats in the form of tablets (at a dose of 200 mg/kg) resulted in a significant increase in intestinal absorption, as evidenced by a 22% improvement in the bioavailability, whereas dilept alone showed an absolute bioavailability of less than 1%.

[Functional reserves of humans in North condition and its providing of fat-soluble vitamins].

It was been examined 810 healthy peoples inhabited in Russian European North. It was been shown that more than 35% of examined person from different group have lowered serum level of retinol and alpha-tocopherol. Described that alpha-tocopherol deficits occur more often and proposed that it cased as a result of free radical oxidation typical for North inhabitances.

[Polymorphism of the apolipoprotein E gene (APOE) in the populations of Russia and neighboring countries].

Allele and genotype frequencies for the locus encoding apolipoprotein E, involved in the regulation of lipid metabolism (APOE), were evaluated in 16 populations representing 12 ethnic groups (a total of 1103 subjects) from Russia and neighboring countries. In the populations examined, the frequencies of allele epsilon4, which is the risk factor of Alzheimer's disease and coronary heart disease, varied from less than 5 to more than 20%, while the variation of the major epsilon3 allele in these populations ranged from less than 75 to 95%. The frequencies of alleles epsilon3 and epsilon4 were 0.714 and 0.205 in Saami, 0.734 and 0.149 in Maris, 0.841 and 0.122 in Evenks, 0.788 and 0.163 in Buryats, 0.764 and 0.202 in Chukchi, 0.875 and 0.075 in Iranians, 0.956 and 0.044 in mountain-dwellers of the Pamirs, 0.771 and 0.094 in Ukrainians, and 0.795 and 0.091 in Belarussians, respectively. In Russians from different regions of the country, the frequencies of these alleles were 0.728 and 0.139 (Kostroma), 0.795 and 0.105 (Moscow), 0.857 and 0.092 (Rostov-on-Don), and 0.824 and 0.083 (Krasnodar), respectively. The latitudinal distribution of the APOE epsilon3 and epsilon4 allele frequencies in the populations examined was comparable to the frequency distribution pattern of these alleles in other populations of Eurasia.

[Uric acid, apo-E and apo-C3 correlation in normo- and hyperlipidemia].

AIM: To investigate correlations between the levels of uric acid and apo-E in patients with normo- and hyperlipidemia. MATERIAL AND METHODS: Serum lipids, apolipoprotein spectrum and uric acid levels were measured with Chronolab (Switzerland) kits in 78 patients: 58 with normolipidemia and 25 patients with hyperlipidemia of type IIa and IIb. RESULTS: Significantly higher levels of apo-E were registered in patients with hyperlipidemia than in patients with normolipidemia, but there were no differences by content of uric acid. A comparative correlation analysis detected a significant correlation between uric acid levels and apo-E in both groups but in normolipidemic patients the correlation was positive while in hyperlipidemic patients it was negative. CONCLUSION: Hyperlipidemia provokes inversion of correlation between the levels of uric acid, apo-E and apo-C3. A rise of apo-C3 may serve an adaptive mechanism of inhibition of apo-E induced hyperlipidemia.

Association and linkage of juvenile MS with HLA-DR2(15) in Russians.

The aim of this study was to determine the role of the HLA-DRB1 gene [6p21] in susceptibility to juvenile MS (JMS) (age at onset < or =15 years) of children of Russian descent. Association of DR2(15) with JMS has been found by the comparison of patients with JMS with both unrelated and affected family-based healthy controls. The linkage of DR2(15) with JMS was shown by transmission disequilibrium test. There were no significant differences in the frequencies of DRB1 alleles and genotypes between 56 patients with JMS and 234 patients with MS with age at onset > or =16 years.

Sweet's syndrome as an initial manifestation of pediatric human immunodeficiency virus infection.

We report a 3-month-old infant in whom Sweet's syndrome was a presenting manifestation of pediatric human immunodeficiency virus infection. Although rare in children, Sweet's syndrome may be associated with certain infections and malignancies. The diagnosis of Sweet's syndrome in a child should always prompt a thorough evaluation to assess for an associated systemic disease.

The new trends in survival improvement require a revision of traditional gerontological concepts.

In 1960, Strehler and Mildvan (SM) theoretically predicted that the parameters of the Gompertz approximation to a mortality curve are negatively correlated. This means that the changes in the human mortality rate resulting from improvement in living standards, progress in health care or the influence of other factors must follow certain regularities prescribed by dependence between the Gompertz parameters. Such dependence, called SM correlation, was then confirmed in a number of empirical studies using period data on human mortality. Since the SM theory was based on the cohort model of mortality, it was tacitly assumed that period and cohort SM correlation patterns are similar. The remarkable stability of the SM correlation pattern revealed in these studies was often regarded as manifestation of a universal demographic law regulating changes in the age pattern of mortality rates. In this paper, we investigated trends in mortality decline in France, Japan, Sweden and the United States. In contrast with traditional expectations, we found that the SM correlation pattern was relatively stable only in certain periods of a population's survival history. Recently, several new correlation patterns emerged and, despite some differences in the timing of the changes, the new patterns are remarkably similar in all four countries. Contrary to traditional expectations, the patterns are not the same for cohort and period mortality data when SM correlations are calculated for France, Sweden and the United States. We show that some changes in the patterns of SM correlation admit interpretation in terms of a biological mechanism of individual adaptation (survival trade off). Some other patterns, however, contradict basic postulates of the SM theory. This indicates the need for revision of traditional concepts establishing the relationship between physiological and demographic patterns of aging.

Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly.

The human sirtuin 3 (SIRT3) gene encodes a putative mitochondrial NAD-dependent deacetylase (SIRT3) which belongs to the evolutionary conserved family of sirtuin 2 proteins. Studies in model organisms have demonstrated that SIR2 genes control lifespan, while no data are available regarding a possible role of SIRT3 in human longevity. By analysing the genotype-specific survival function relevant to the G477T marker of SIRT3, we found that in males the TT genotype increases (p=0.0272), while the GT genotype decreases (p=0.0391) survival in the elderly. Since SIRT3 lies in a chromosomal region (11p15.5) where four genes potentially associated with longevity are located (HRAS1, Insulin-like Growth Factor 2, Proinsulin, and Tyrosine Hydroxylase) we tested for linkage-disequilibrium between G477T alleles and alleles of the above genes. The disequilibrium was not significant in any case, thus suggesting that SIRT3 itself, or a gene strictly linked to SIRT3, may have a role in human longevity.

Have the oldest old adults ever been frail in the past? A hypothesis that explains modern trends in survival.

Three important results concerning the shape and the trends of the human mortality rate were discussed recently in demographic and epidemiological literature. These are the deceleration of the mortality rate at old ages, the tendency to rectangularization of the survival curve, and the decline of the old age mortality observed in the second part of the 20th century. In this paper we show that all these results can be explained by using a model with a new type of heterogeneity associated with individual differences in adaptive capacity. We first illustrate the idea of such a model by considering survival in a mixture of two subpopulations of individuals (called "labile" and "stable"). These subpopulations are characterized by different Gompertz mortality patterns, such that their mortality rates cross over. The survival chances of individuals in these subpopulations have different sensitivities to changes in environmental conditions. Then we develop a more comprehensive model in which the mortality rate is related to the adaptive capacity of an organism. We show that the trends in survival patterns experienced by a mixture of such individuals resemble those obtained in an analysis of empirical data on survival in developed countries. Lastly, we present evidence of the existence of subpopulations of phenotypes in both humans and experimental organisms, which were used as prototypes in our models. The existence of such phenotypes provides the possibility that at least part of today's centenarians originated from an initially frail part of the cohort.

Generalized pustulation as a manifestation of the anticonvulsant hypersensitivity syndrome.

BACKGROUND: -The anticonvulsant hypersensitivity syndrome is characterized by the development of fever, rash, lymphadenopathy, and hepatitis, and is associated with leukocytosis and eosinophilia. This article describes the unusual development of a follicular pustular eruption in two patients as a manifestation of this syndrome. OBSERVATIONS: -This pustular eruption most commonly develops on the face and scalp but may subsequently become generalized. While cultures of the pustules are negative, biopsy specimens reveal a dilated follicular infundibulum filled with neutrophils. Recognition of cutaneous pustulation as a potential manifestation of this syndrome is important, as a generalized pustular eruption developing in a febrile patient can easily be confused with an infectious process. CONCLUSIONS: -The anticonvulsant hypersensitivity syndrome may present with a follicular pustular eruption rather than the more commonly associated macular or papular rash or erythroderma. The three most commonly used anticonvulsants, phenytoin, phenobarbital, and carbamazepine, can each produce an identical hypersensitivity reaction. In addition, in vitro testing has demonstrated that approximately 80% of patients tested to all three medications had positive reactions to each. Furthermore, with in vitro testing researchers are able to predict which anticonvulsants are safe to use, thereby allowing for prospective individualization of therapy. However, this technology is not yet available for widespread use.

Osteomyelitis of the distal phalanges in three children with severe atopic dermatitis.

Three children with severe, secondarily infected atopic dermatitis since infancy developed osteomyelitis of the distal phalanges of the hands. The insidious onset of one or more distal subungual black macules was followed by edema, erythema, and pain in the involved fingers. No child had an elevated erythrocyte sedimentation rate or fever, but all had roentgenographic or scintigraphic evidence of bony destruction. In two children, Staphylococcus aureus grew from skin surface cultures; S aureus also grew from nail bed and osseous cultures of the distal phalanges; Streptococcus viridans grew from one child's nail bed. All children had prolonged hospitalizations. In two children, laboratory evaluation of immunologic function disclosed normal findings. We postulate that intense scratching of infected skin coupled with minor trauma to the fingertips created distal subungual microabscesses that spread contiguously to the underlying bone.