[Diagnostics and treatment of large splenic artery aneurysms illustrated by two clinical cases presentation]. / Diagnostika i lechenie bol'shikh anevrizm selezenochnoi arterii na primere dvukh klinicheskikh nabliudenii.

The authors analyze the clinical course of large splenic artery aneurysms (SAA) accidentally identified in two patients. In the first case 4.5×4.0 sm aneurysm was circumstantially discovered while providing the multispiral computer coronary angiography, and it was interpreted as a pancreatic gland cyst. Four years later on the next spiral computer tomography (SCT) provided also under another prescription ASA was found by means of contrast intensifying, and it had reached the size of 5.1×6.3×6.2 sm. In the second patient suffering from hepatic cirrhosis and hospitalized because of esophagogastric bleeding the deforming posterior ventricle wall lump was discovered during the laparotomy and stomach operating exploration. By providing the lump needle punction arterial blood was observed. During the upcoming SCT with contrast intensifying this lump was verified as a saccular SAA sized 7.8×5.7 sm. In both cases the endovascular proximal splenic artery embolization was successfully applied as the treatment.

Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer.

Modeling and integral X-ray, optical, and MRI visualization of multiorgan metastases of orthotopic 4T1 breast carcinoma in BALB/c mice.

A model of highly metastasizing orthotopic allogeneic breast carcinoma was reproduced and standardized in experiments on BALB/c mice. 4T1 cells characterized by high metastatic activity were transfected with red fluorescent protein (RFP) gene or firefly luciferase (Luc2) gene. Unmodified 4T1 cells and modified 4T1-RFP and 4T1-Luc2 cells were subcutaneously injected to mature female mice into the second mammary fat pads. Quantitative evaluation of the primary node and visceral metastases was performed using magnetic-resonance imaging, X-ray and optical tomography. Modification of 4T1 cells with RFP gene considerably reduced their invasive and metastatic potential and led to spontaneous regression of the primary tumor in 20% cases. Modification of 4T1 cells with Luc2 gene had practically no effect on proliferative, invasive, and metastatic characteristics of the tumor and provided the possibility of quantitative analysis of the primary tumor dynamics by the luminescence intensity. The survival median in mice receiving unmodified 4T1 cells and transfected 4T1-RFP and 4Т1-Luc2 cells was 32, 42, and 38 days, respectively. Neither primary node nor tumor metastases accumulated gadolinium-containing contrast agent and Alasens fluorescent tracer. After implantation of 4T1 and 4Т1-Luc2 cells, multiple metastases were more often detected in the lungs, liver, spleen, spine, and regional lymph nodes and less frequently in the brain, which corresponded to metastasizing profile of human breast cancer. The developed model of orthotopic breast carcinoma 4T1 in BALB/c mice with complex detection of multiple organ metastases using X-ray microCT, optical, and MRI can be recommended for preclinical studies of new antitumor preparations.

Familial Mediterranean FeVer gene (MEFV) mutations as a modifier of systemic lupus erythematosus.

The objective of this study was to assess the prevalence of the Mediterranean FeVer (MEFV) gene mutations in systemic lupus erythematosus (SLE) patients and their effect on organ involvement, as well as disease activity and severity. The frequencies of three familial Mediterranean fever-related MEFV gene mutations (M694V, V726A and E148Q) were investigated in 70 SLE patients. Organ involvement, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were correlated with mutation carriage. Eleven of 70 patients (15.7%) were found to carry an MEFV mutation. A single patient harbored two mutations, E148Q and V726A, without overt familial Mediterranean fever while the rest were heterozygous carriers. Four of the 11 carried an M694V mutation, four carried V726A and two carried E148Q. The majority of MEFV mutation carriers were Sephardic while non-carriers were mainly of Ashkenazi origin (72.7% vs. 45.7% and 47.4% vs. 9.1%, respectively, p = 0.02). SLE onset was significantly earlier in MEFV carriers (27.6 ± 9.7 vs. 38.2 ± 15.5 years, in carriers vs. non-carriers, p = 0.02). Hematologic and serologic parameters were comparable among mutation carriers and non-carriers. Febrile episodes were more common among MEFV mutation carriers (45.4% vs. 15.2%, p = 0.035) and there was a trend for excess episodes of pleuritis as well (54.5% vs. 23.7%, p = 0.06 in carriers vs. non-carriers, respectively). The frequency of secondary anti-phospholipid antibody syndrome was equivalent among the groups. Conversely, compound urinary abnormalities and renal failure was not observed among MEFV carriers yet was present in 33.4% and 18.6% of non-carriers (p = 0.027 and 0.19, respectively). SLICC damage index and SLEDAI activity index did not differ significantly between the groups. MEFV mutation carriage appears to modify the SLE disease phenotype in that it contributes to an excess of inflammatory manifestations such as fever and pleuritis on the one hand, while thwarting more severe renal involvement on the other.

Angiotensin-converting enzyme genotype and encephalopathy in Chernobyl cleanup workers.

BACKGROUND AND PURPOSE: To identify, using a genetic model, a key role for the renin-angiotensin system (RAS) in the development of dyscirculatory encephalopathy (DE) in Chernobyl cleanup workers (CCW). The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene denotes a substantial individual variation in RAS activity with the D-allele being associated with higher ACE activity. METHODS: Ninety-three male, Caucasian CCW were recruited from those under regular review at the All-Russia Centre of Emergency and Radiation Medicine, St. Petersburg. The presence or absence of DE was determined using existing institutional guidelines. ACE genotype was determined using internationally accepted methodologies. RESULTS: Angiotensin-converting enzyme genotype distribution in 59 subjects with DE was II: 10 (17%), ID: 31 (53%), DD: 18 (30%), D-allele frequency 56.8%. Whereas in those without the condition the distribution was II: 12 (35%), ID: 19 (56%), DD 3 (9%) and D-allele frequency 35.9% (P = 0.02). CONCLUSIONS: These data are the first to identify an association between the ACE D-allele and DE in CCW. They provide evidence of a significant role for the RAS in the development of DE and suggest that clinical trials of ACE inhibition would be profitable in this group.

[Radiation and nonradiation factors in thyroid pathology development for Chernobyl cleanup workers--residents of Mayak PA affected zone].

Thyroid state study was been carried out for Chernobyl NPP accident liquidators living in Ozyorsk, the city, located in the nuclear facility affected zone (Mayak PA). In total 531 individuals were examined. Thyroid assessment was made basing on physical examination, on ultrasound study and on hormones measurement of thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibody. Screening revealed thyroid pathology for 27% of clean-up workers. As a result of the study carried the following conclusions were made: thyroid disease prevalence among the Ozyorsk residents participated in the breakdown elimination after Chernobyl accident was not differ from the individuals who didn't take part in this work; the prevalence of thyroid disease in liquidators was significantly connected with non radiation risk factors: with gender (for women compared to men), RR = 4.0, 95% CI 2.9-5.5; with age (over 60 years old vs under 60 years old), RR for women was 1.7; 95% CI 1.0-3.0 and for men -1.9; 95% CI 1.1-3.2; with hereditary predisposition, RR for autoimmune thyroiditis was 3.3, 95% CI 1.4-7.9.

[Use of allicor to lower the risk of myocardial infarction].

The aim of the study was to investigate the effects of allicor (a long-action garlic-based preparation) on the risk of acute myocardial infarction (MI) and sudden death (SD) in patients with coronary artery disease (CAD). Fifty one CAD patients were included in this double-blind placebo-controlled study. The prognostic risk of MI and SD during ten following years was counted using Cox proportional hazards model based on the results of Munster study. Allicor administered for 12 months was demonstrated to reduce absolute ten-year risk of acute MI and SD 1.5 times in men and 1.3 times in women. The reduction in calculated risk parameters was associated with changes in blood plasma lipid profile, the most significant of which was reduction in the level of low density lipoprotein cholesterol (p < 0.05) by 32.9 mg/dl in men and 27.3 mg/dl in women. The results of this study demonstrate that allicor is effective for the reduction of multifactor MI and SD risk as a means of secondary CAD prophylaxis.

Common FMF alleles may predispose to development of Behcet's disease with increased risk for venous thrombosis.

BACKGROUND: Behcet's disease (BD) is an inflammatory disorder of unknown cause, associated with vasculitis. Arterial or venous thrombosis occurs in about 25% of BD patients. Familial Mediterranean fever (FMF) is another inflammatory disorder, which stems from mutations in the FMF gene (MEFV) and shares a number of features with BD. OBJECTIVE: MEFV analysis in patients with BD suggests that mutated MEFV may act as a susceptibility gene in BD. We studied the rate and the clinical correlates of MEFV mutations in Israeli BD patients. METHODS: Included were 54 BD patients who satisfied the International Study Group criteria for BD. All BD patients were genotyped using polymerase chain reaction (PCR) and restriction enzyme analysis for the three most common MEFV mutations (M694V, V726A, and E148Q). The association between BD manifestations and MEFV alleles was analysed. RESULTS: Twenty-one BD patients were found to carry a single MEFV mutation and three additional patients were compound heterozygotes, a frequency significantly higher than that expected for ethnically matched healthy individuals. There were no statistically significant differences between carriers and non-carriers with respect to gender, frequency of HLA B5 antigen, cutaneous lesions, joint disease, and severity score. However, carriers did experience thrombosis more often [54% vs. 17%, p<0.005, odds ratio (OR) = 6.9, 95% confidence interval (CI) 1.75-26.9] and uveitis less often (20% vs. 40%, p<0.05, OR = 0.2, 95% CI 0.04-0.92). CONCLUSIONS: MEFV appears to be a susceptibility and modifier gene in BD.

Thyroid abnormalities associated with protracted childhood exposure to 131I from atmospheric emissions from the Mayak weapons facility in Russia.

Between 1948 and 1960, the Mayak nuclear weapons facility in Ozyorsk, Russia discharged relatively high levels of radionuclides, primarily (131)I, into the atmosphere, resulting in appreciable exposure to the residents of Ozyorsk. To evaluate the association between thyroid diseases and childhood exposure to radioiodines, we screened 894 Ozyorsk residents born between 1952 and 1953. The study population was comprised of 581 exposed individuals living in Ozyorsk during the years of heaviest exposure and 313 nonexposed individuals who moved to Ozyorsk when radiation exposure from Mayak largely had ended. The screening protocol included a patient interview, palpation of the thyroid, cervical lymph nodes and salivary glands, an ultrasound examination, and measurement of fT4, TSH and TPOAb. Twenty-eight percent of the study group was diagnosed with a thyroid abnormality. The prevalence of nodular disease was significantly higher in the exposed group (20.7%) compared with the nonexposed (14.4%) group (relative risk = 1.4, 95% CI = 1.1; 1.9). Risks were larger for solitary nodules and for nodules > or = 10 mm in diameter. Expansion of the study to increase the number of persons screened as well as detailed dose estimation would offer an unique opportunity to evaluate thyroid disease in relation to chronic exposure to radioiodines during childhood.

Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene.

BACKGROUND: Pyrin is a newly recognised intracellular regulator of inflammation, and mutations in MEFV, the gene encoding pyrin, are the cause of familial Mediterranean fever. OBJECTIVE: To determine if known mutations of MEFV are associated with rheumatoid arthritis (RA) morbidity or can modify RA severity. METHODS: The frequency of the three most common MEFV mutations: M694V, V726A, and E148Q, was determined in 98 Israeli patients with RA (74 women, 24 men) and compared with that in 100 healthy subjects matched for origin. RA severity was determined using a new clinical score of 126 grades. The median severity score of mutation carrier and non-carrier groups was compared after confounding measures were eliminated by logistic regression. RESULTS: 17/98 (17%) patients with RA (all women) were heterozygous for common MEFV mutations, predominantly E148Q (12 patients), and one patient was homozygous for the V726A mutation. The overall mutation rate was comparable between patients with RA and healthy subjects. Patients carrying a mutation had a higher median severity score than the non-carrier group (42 v 29, p = 0.0005). The logistic regression model assigned a 15-fold odds ratio for severe RA in carriers, after adjusting for sex, presence of rheumatoid factor, age at onset, and disease duration (n = 97, p = 0.01, 95% CI 1.74 to 128). CONCLUSION: MEFV, and particularly the E148Q mutation, is an independent modifier of the clinical manifestations of RA. This is the second Th1-type autoimmune disease in which MEFV mutations have been shown to aggravate the clinical status.

[Allicor efficacy in lowering the risk of ischemic heart disease in primary prophylaxis].

AIM: To assess effects of allicor (a long-acting garlic drug) on the risk of ischemic heart disease (IHD) in primary prophylaxis of cardiovascular diseases. MATERIAL AND METHODS: A double blind placebo-controlled study investigated for a year changes in multifactorial risks of cardiovascular events or their complications in 167 patients with hyperlipidemia free of IHD. RESULTS: In men, intake of allicor for 12 months resulted in a 10.7% reduction of a 10-year absolute risk to develop IHD (p < 0.05) and decreased a 10-year absolute risk of acute myocardial infarction and sudden death by 22.7% (p < 0.05). In women, allicor prevented age-related cardiovascular risk (p < 0.05). Among lipid parameters, the greatest fall was observed for total cholesterol and LDLP cholesterol (p < 0.05) in men by 27.9 and 22.5 mg/dl, in women--by 11.4 and 10.8 mg/dl, respectively. CONCLUSION: Allicor is effective in reducing multifactorial risk of cardiovascular diseases.

[Electroencephalography monitoring at total and managed hyperthermia to 44 degrees C]. / Elektroéntsefalograficheskii monitoring pri obshchei upravliaemoi gipertermii do 44 gradusov C

In 34 patients the abstinence syndrome was treated by hypothermia (HT) with the EEG monitoring. HT was carried out under the general propofol-fentanil anesthesia. HT was achieved in the "Hirana" bath. The temperature was increased gradually by 1 degree C per 5 minutes up to 44 degrees C. EEG was recorded before anesthesia, as well as during and after the procedure. On the initial EEG alpha- and beta-rhythms were predominant. Under the anesthesia both alpha-rhythm frequency and amplitude were enhanced, spikes and wave discharges appeared. Under HT (t = 40-42 degrees C) low voltage and wave slowing were recorded. In the range t degree--42.5-43.4 degrees C EEG registered the appearance of clinically significant "biological break point", which was followed by neuropeptide destruction. At t degree--43-44 degrees C acute suppression and, then, electrocerebral silence were observed in a majority of patients. At the end of the procedure (t = 39 degrees C) EEG returned to the initial recording.

Technique for detecting changes in fluorescence lifetime by means of optoelectronic circuit auto-oscillation.

We present a new, simple, inexpensive, and highly precise approach to excited-state fluorescence-lifetime-based measurements. The detection system consists of a closed-loop optoelectronic arrangement containing a radio frequency resonance amplifier, a fluorescence excitation light source, a fiber-optic delay line, and a photodetector. The system exhibits auto-oscillations in the form of intensity modulation. The oscillation frequency varies with the modulation phase shift of the fluorescent light. This frequency is used as the detection parameter, which is advantageous because frequency may be measured easily, inexpensively, and with high precision. This technique is well suited for chemical or biosensor applications.

Chronic recurrent multifocal osteomyelitis associated with chronic inflammatory bowel disease in children.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease of children characterized by aseptic inflammation of the long bones and clavicles. No infectious etiology has been identified, and CRMO has been associated with a number of autoimmune diseases (including Wegener's granulomatosis and psoriasis). The relationship between CRMO and inflammatory bowel disease is poorly described. Through an internet bulletin board subscribed to by 500 pediatric gastroenterologists, we identified six inflammatory bowel disease patients (two with ulcerative colitis, four with Crohn's colitis) with confirmed CRMO. In all cases, onset of the bony lesions preceded the onset of bowel symptoms by as much as five years. Immunosuppressive therapy for the bowel disease generally resulted in improvement of the bone inflammation. Chronic recurrent multifocal osteomyelitis should be considered in any inflammatory bowel disease patient with unexplained bone pain or areas of uptake on bone scan. CRMO may be a rare extraintestinal manifestation of inflammatory bowel disease; alternatively, certain individuals may be genetically predisposed to the development of both diseases.

AP-3: an adaptor-like protein complex with ubiquitous expression.

We have identified two closely related human proteins (sigma3A and sigma3B) that are homologous to the small chains, sigma1 and sigma2, of clathrin-associated adaptor complexes. Northern and Western blot analyses demonstrate that the products of both the sigma3A and sigma3B genes are expressed in a wide variety of tissues and cell lines. sigma3A and sigma3B are components of a large complex, named AP-3, that also contains proteins of apparent molecular masses of 47, 140 and 160 kDa. In non-neuronal cells, the 47 kDa protein most likely corresponds to the medium chain homolog p47A, and the 140 kDa protein is a homolog of the neuron-specific protein beta-NAP. Like other members of the medium-chain family, the p47A chain is capable of interacting with the tyrosine-based sorting signal YQRL from TGN38. Immunofluorescence microscopy analyses show that the sigma3-containing complex is present both in the area of the TGN and in peripheral structures, some of which contain the transferrin receptor. These results suggest that the sigma3 chains are components of a novel, ubiquitous adaptor-like complex involved in the recognition of tyrosine-based sorting signals.

Copper-dependent degradation of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p in the apparent absence of endocytosis.

The cell surface protein repertoire needs to be regulated in response to changes in the extracellular environment. In this study, we investigate protein turnover of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p, in response to a change in extra-cellular copper levels. As Ctr1p mediates high affinity uptake of copper into the cell, modulation of its expression is expected to be involved in copper homeostasis. We demonstrate that Ctr1p is a stable protein when cells are grown in low concentrations of copper, but that exposure of cells to high concentrations of copper (10 microM) triggers degradation of cell surface Ctr1p. This degradation appears to be specific for Ctr1p and does not occur with another yeast plasma membrane protein tested. Internalization of some Ctr1p can be seen when cells are exposed to copper. However, yeast mutant strains defective in endocytosis (end3, end4 and chc1-ts) and vacuolar degradation (pep4) exhibit copper-dependent Ctr1p degradation, indicating that internalization and delivery to the vacuole is not the principal mechanism responsible for degradation. In addition, a variant Ctr1p with a deletion in the cytosolic tail is not internalized upon exposure of cells to copper, but is nevertheless degraded. These observations indicate that proteolysis at the plasma membrane most likely explains copper-dependent turnover of Ctr1p and point to the existence of a novel pathway in yeast for plasma membrane protein turnover.

[The predictive value of cyclic nucleotide ratio in the prognosis of experimental tumors]. / Informativnost' testa sootnosheniia tsiklicheskikh nukleotidov pri prognozirovanii zlokachestvennykh opukholei v éksperimente.

The report deals with the predictive value of a procedure for lifetime detection of tumor in experimental animals. The database included the results of regular cAMP/cHMP tests carried out in 54 rats with radionuclide-inducted tumors and 24 tumor-free rats. The data were processes by statistical methods and the informative value was determined on the basis of standard recommendations. The test was shown to have high sensitivity (85.2%), sufficient predictive value (73%) and diagnostic effectiveness (68%). Application of the test in groups of humans at high risk of tumor development is discussed.

Avaliaçäo dos projetos de educaçäo sexual; relatório / Evaluation of sex education project; report

Apresenta os dados de avaliaçäo dos Projetos de Educaçäo Sexual apoiados pela Fundaçäo Odebrecht e desenvolvidos nas cidades de Salvador e Rio de Janeiro

Thiol-reducing agents and calcium perturbants alter intracellular sorting of immunoglobulin M.

The secretory form of IgM (sIgM) undergoes developmentally regulated intracellular sorting and transport, as demonstrated by the distinct assembly patterns and intracellular fate exhibited by its mu heavy chain (microseconds). In the 38C B lymphocytes, microseconds-containing monomers are retained and degraded intracellularly, whereas in the 38C-derived D2 hybridoma, microseconds-containing polymers are secreted. Here we show that sorting of sIgM is impaired in the presence of the thiol-reducing agent beta-mercaptoethanol or when cellular calcium sequestration is perturbed either with the Ca2+ ionophore A23187 or with thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase. Under these conditions, sIgM evades retention/degradation in the 38C cells, resulting in its enhanced secretion. Conversely, in the D2 cells, secretion is strongly attenuated, and sIgM is partly degraded. Both cell types secrete unusually processed sIgM, which is completely resistant to endoglycosidase H, unlike the partially sensitive sIgM secreted in the usual manner, indicating terminal glycosylation of all carbohydrate moieties of microseconds. Moreover, secretion is no longer restricted to fully assembled polymeric sIgM, and in both cell types under Ca2+ perturbation preferentially hemimeric and monomeric assembly intermediates are detected in the medium. Our results suggest that the intracellular fate of sIgM is collectively determined by several sorting events that confer sIgM retention/degradation, ensure sIgM secretion from D2 cells, and prevent the arrival of assembly intermediates to the cell surface. All of these sorting events appear to require high Ca2+ concentration and oxidizing thiol redox state, the conditions that prevail in the lumen of the endoplasmic reticulum. Thus, thiol and calcium are implicated as modulators of intracellular traffic.