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The Aim of the Study: Gastroesophageal reflux disease is a common disease with a multifactorial pathogenesis. Our aim was to analyse the role of the Gastroesophageal Disease Questionnaire in diagnosing reflux disease in the population of the Republic of Macedonia., Methods: The questionnaire on the severity of the symptoms related to GERD was used. An evaluation of the distal portion of the oesophagus was carried out in all patients with positive questionnaire results. All mucosal injury was classified by the Los Angeles criteria (LA)., Results: 642 patients were included. 58.73% females, with an average age of 37.5±8.2. Females had a higher BMI than males 26.8±4.1 vs. 24.9±3.8 p<0.001. Of the total number of examinees (642 patients), in those with erosive reflux disease and also in those with nonerosive reflux disease, as shown respectively in endoscopy, the sensitivity of the RDQ was 100%, and the specifity was 0%. The100 sensitivity means that the questionnaire verified/diagnosed patients with erosive reflux disease with 100% certainty., Conclusions: RESULTS were found in some studies comparing the positive Reflux Disease Questionnaire and the level of erosive esophagitis (LA classification). This study provides evidence that the RDQ represents a viable instrument for assessing symptom severity and response to treatment in clinical trials of patients with GERD, but in patients with a high score, endoscopic evaluation should not be excluded.

Endoscopic retrograde cholangiopancreatography provides precise imaging of malignant biliopancreatic strictures and allows palliative treatment with endoscopic stenting. Initial successful biliary stenting can be achieved in about 69-100% of patients with pancreatic head malignancies. Preliminary data from our Clinic reported a much lower success rate of endoscopic biliary stenting in obstructive jaundice caused by pancreatic head malignancies. These findings may be because patients are referred at more advanced stages, which could contribute to the lower success rate of biliary stenting. We aimed to determine the success rate of endoscopic biliary stenting prospectively in 50 patients with pancreatic head malignancies and to asses if clinical, laboratory and ultrasound findings can be predictive of success and safety in biliary stenting. Initial successful biliary stenting was achieved in 70% of our patients. No major complications (perforation, severe pancreatitis, massive bleeding, death) were noted. We were able to identify factors predictive of a lower success rate which were associated with a more advanced disease and a longer delay before treatment. Based on our results, we conclude that ERCP should be offered without delay as a primary treatment option for all patients with unresectable pancreatic head malignancy and as a possible treatment option in patients with resectable malignancy who are poor candidates for surgery.

This investigation was aimed at the evaluation of holotopy, skeletotopy and sintopy of human liver in early fetal period. In 60 human fetuses aged 16-24 weeks, a quantitative characteristic of liver topography was obtained using a modification of N.I. Pirogov method and multiplane histitopograms with the application of multidimensional coordinate system. Fetal liver sintopy was described in sections performed in different planes and its peculiarities in the period studied was emphasized. As the standard sections to be used for the ultrasonographic and magnetic resonance diagnostics of fetal liver, authors recommend the horizontal sections, made at the level of IX-XII thoracic vertebrae.

The aim of the study is to evaluate the contrast enhanced power doppler technique as a method to detect and differentiate vascular patterns of focal liver lesions. Fourty-nine patients with focal liver lesions were included in the study, twenty-nine of them with malignant liver lesions (9 HCC, 20 metastatic), twenty patients with benign lesions (12 haemangiomas, 5 focal nodular hyperplasia, 3 focal steatosis). In all patients classic B-mode and power doppler sonography was performed prior to administration of the contrast medium Levovist (300 mg/ml) and a power doppler examination subsequent to medium administration. Contrast administration led to lowering the number of "no-flow" lesions from 19 to 11. Postcontrast scan analysis revealed markedly enhanced flow in 15 cases in comparison to only 4 in pre-contrast examinations. The pre-contrast power doppler showed central flow in 7, and peripheral in 26 focal liver lesions. On the other hand, the postcontrast study revealed a central flow in 14, and peripheral in 34 focal liver lesions. Statistical significance between pre- and post-contrast power doppler detection of vascularization existed in malignant focal liver lesions and haemangiomas. The same pre- and post-contrast evaluation proved to be statistically non-significant in the focal nodular hyperplasia and focal steatosis groups. Administration of contrast medium enables a better visualization of intratumor blood vessels in focal liver lesions. This, in combination with the power doppler technique, brings such scans close to angiographic findings.

Indications for puncture or excision biopsy were significantly higher in the study group (7.5%) as compared with control (3.5%) (p < 0.01) in a randomized prospective controlled trial of a comprehensive breast cancer screening (123,748) carried out in the framework of a self-examination education program. In the self-examination group, detection rates were higher both for benign (1.1%) and malignant (0.85%) tumors than in control (0.5% and 0.69%, respectively) (p < 0.05). Early stage (T1NOMO, Tis) distribution difference in the study group and controls was insignificant--23 and 17.6%, respectively. Compliance with the program requirements including monthly or bimonthly self-examination was followed by higher 15-year survival rates (53.2%) in 70-75% as compared with controls(45.8%) (p = 0.05105): yet it did not affect mortality.

The spike (S) and hemagglutinin/esterase (HE) of bovine coronavirus (BCV) are the two envelope proteins that recognize the same receptor-determinant of 9-O-acetylneuraminic acid on host cells. However, the precise and relative roles of the two proteins in BCV infectivity remain elusive. To unequivocally determine their roles in viral cytopathogenicity, we developed a system in which phenotypically chimeric viruses were generated by infecting a closely related mouse hepatitis virus (MHV) in cells that stably express an individual BCV protein (S or HE). The chimeric viruses were then used to infect human rectal tumor (HRT)-18 cells that are permissive to BCV but are nonsusceptible to MHV. Using this approach, we found that the chimeric virus containing the BCV S protein on the virion surface entered and replicated in HRT-18 cells; this was specifically blocked by prior treatment of the virus with a neutralizing antibody specific to the BCV S protein, indicating that the BCV S protein is responsible for initiating chimeric virus infection. In contrast, chimeric viruses that contain biologically active and functional BCV HE protein on the surface failed to enter HRT-18 cells, indicating that the BCV HE protein alone is not sufficient for BCV infection. Taken together, these results demonstrate that the S protein but not the HE protein of BCV is necessary and sufficient for infection of the chimeric viruses in HRT-18 cells, suggesting that BCV likely uses the S protein as a primary vehicle to infect permissive cells., ((C)2002 Elsevier Science (USA).)

We presented the data on the abundance of immature instars of the taiga tick Ixodes persulcatus Schuize on the common shrews Sorex araneus L. in natural foci of tick-borne encephalitis in the south of Western Siberia. Basing on the results of virological and serological studies we demonstrated a low effectiveness of this host species as a donor of disease agent strains, which are predominant in the territory under study, for ticks feeding on shrews. The analysis of samples taken from the young shrews in winter and spring using reverse RNA transcription with polymerase chain reaction and ELISA revealed occurRence of subvirion components of the tick-borne encephalitis (RNA and capsid protein E) ether in brain, liver or spleen in 90 percent of shrews (n = 42). Neither hemagglutination antigen nor infectious virus have been detected. We discussed a possible epizootic role of the maintenance of non-infectious tick-borne encephalitis virus in overwintering animals.

Bacteria were isolated from the nasopharynx of BALB/c mice and electroporated with pUR290(NS1)2 containing two copies of tick-borne encephalitis virus (TBEV) strain Sofjin NS1 under the control of the lac promoter. The plasmid persisted in transformants for at least ten passages. The NS1 gene expression was detected in Gram-negative enterobacteria via immunoblotting with monoclonal antibodies against TBEV nonstructural glycoprotein NS1. Recombinant NS1 was detected in bacterial cells and in the culture medium. Intranasal immunization with recombinant bacteria activated production of antibodies against NS1 in serum of BALB/c mice. The humoral immune response to NS1 failed to protect immunized mice from a TBEV challenge.

BALB/c mice were immunized with recombinant plasmid DNA pSVK3-ENS1 and pcDNAI-NS3 containing, respectively, genes E-NS1 and NS3 of tick-borne encephalitis (TBE) virus. Antibodies to TBE virus proteins were detected in the blood sera of the immunized animals by the method of the enzyme immunoassay. Though the titers of virus-specific antibodies in the sera of mice immunized with protein vaccines exceeded those registered after immunization with DNA vaccines, essential protective immunity was observed after the use of both vaccines.

Training in breast self-examination (BSE) technique involved 57,712 women, aged 40-64, at 14 out of randomly selected out-patient hospitals in St. Petersburg (1985-1989). Another 64,759 women selected at another 14 out-patient hospitals were in control. All patients with detected tumor pathology of the breast were biopsied and treated at the Institute's Clinic. The study focused on breast cancer incidence, survival and mortality. More women in the BSE group sought medical advice for suspected pathology (4,300) than those in control (2,438; p < 0.05). There were 493 cases of breast cancer in the BSE group with 157 fatalities, 446 cases of breast cancer with 167 fatalities in the control group. There was no significant difference in tumor stage. Nine-year survival (after Kaplan-Meyer) from the time of tumor detection was 65% in the study group and 55% in control (log rank 0.774; p > 0.05). There has been no significant difference in death rates in both groups for the past ten years. The study is to continue until the year 2001.

Hybridomas secreting monoclonal antibodies (Mab) to tick-borne encephalitis (TBE) virus are obtained. Immunodiffusion showed that 3 Mabs to TBE protein NS3 belong to class IgM and the rest to IgG1. Mabs to TBE protein NS1 were tested in hemagglutination inhibition, complement fixation, neutralization, and protection tests. Only 1 hybridoma produced Mab specific for protein NS1 of TBE strain Sofyin, the rest reacted with the common antigenic determinants of nonstructural TBE complex.

The effectiveness of adjuvant treatment with anthracyclins (adriablastin, doxorubicin) and standard CMF regimens for breast tumors has been compared. The study included 349 patients with stage IIB-IIIA tumors (T1-2N2M0, T3N0-2M0) (mean age-46 years) during 1985-1990 follow-up-60.38 months. In the doxorubicin group, overall 5-year survival was 73 +/- 8%, in the CMF group-62 +/- 8%. Recurrence-free 5-year survival was 62 +/- 8 and 55 +/- 8%, respectively. The differences are not significant. A stage-related analysis established a significant difference in overall survival in patients with T1-2N2M0 tumors (c-sqare 9.92, p < 0.01). However, due to a small number of cases, the phenomenon requires further study. Although adriablastin treatment involved a significantly higher frequency of carciotoxic symptoms, complete alopecia and dyspeptic complication, a systemic administration of cardioxan and effective antiemetic drugs was lacking.

The dynamics in recurrences of pulmonary tuberculosis was analyzed in the areas of Yakutia. The social and clinical characteristics of patients with recurrences and their treatment outcomes are presented in the paper. Recurrences of pulmonary tuberculosis were found to occur more frequently in the areas having a poor epidemiological tuberculosis situation and among socially unprotected groups of the population. Under these conditions, recurrences may occur in 30 years or more after clinical cure of tuberculosis. To treat patients with recurrences in the area presents great difficulties.

In the past 12 years, there were 1.3- and 1.9-fold reductions in the total morbidity rates of tuberculosis and its spread, respectively. However, its morbidity among children showed 3-fold increases. The reduction rate of bacterial excretion became much slower in the past 4 years. Tuberculosis mortality rates tended to rise. At the moment of study, the basic tuberculosis epidemiological parameters were 1.3-1.5 times higher than those in the Russian Federation. At the same time there was a decrease in the efficiency of antituberculous work at all levels.

A third series of randomized evaluation of postoperative (adjuvant) hormone therapy (tamoxifen, sinestrol and orimeten) was carried out in breast cancer patients. The study group involved 1.332 reproductive and postmenopausal females with stage I-III tumors. The investigation established quite a range of 10-year survival evidence versus stage and reproductive status; however, no significant differences were recorded in either of the groups. Untoward side-effects were more frequent when treating with diethyl-stilbestrol (over 30%) than with tamoxifen (3.5%). No significant differences were registered in five-year total and recurrence-free survival in the treatment with orimeten or tamoxifen.

Conservative surgery (sectoral or segmental + axillary dissection) was performed in 278 patients with breast cancer (T1-2N0M0) at the Institute Clinic in 1990-1995. Following thorough morphological examination. 148 patients (53.2%) were selected to form a clinical study group for an investigation of the role of postoperative radiotherapy in the conservative treatment of breast cancer. Two groups-irradiation of the remaining breast tissue and controls-were formed on the basis of randomized data. Follow-up continued 3-60 months (average duration-37.7 months). Local recurrence was detected in 3 out of 73 (4.2%) patients of group I. A similar relapse was detected in 6 out of 75 (8.0%) patients of group II. No significant difference in total survival rates in the two groups was observed (97.3 and 96.0%; p > 0.05).

Although an absolute difference of 10% (65,4 vs. 54,9%) in 5- and 9-year survival in breast cancer patients was recorded between the self-examination and control groups a large-scale randomized population-controlled study of 122,471 females has failed to provide significant differences (Log-rank - 0,774, p > 0.05). No significant decrease in mortality was observed in the self-examination group as compared with the untrained controls. As a result of providing more information to the population on risk factors. twice as many of the trained females consulted oncologists. Also, the number of early detection of breast tumor (T1-2NOMO) in both groups was 1,5-2,5 times that recorded elsewhere. Since 3,55 per 1,000 patients with breast tumors per year, aged 50-59, died of cardio-vascular disease, i.e. 3,1 times the expected 1,16 per 1,000, more attention should be focused on timely diagnosis and treatment of concomitant cardio-vascular pathology.

A total of 107 children with various clinical manifestations of food allergy were examined to investigate the morphological changes of eosinophils under the effect of food allergens. Eosinophil "injury" caused by cow milk allergen was detected in 71.4%, that caused by hen egg white in 82.4%, and that under the effect of fish in 77.8% of the examinees, these data being useful as a laboratory test for the diagnosis of food sensitization. Correlation between the index of eosinophil injury and late reactions to cow milk, as well as increased reactivity to nonspecific stimuli were traced.

Materials of autopsies of 52 children suffering from severe herpetic infection, intrauterine as a rule, were analysed. The etiology of the process was proved by immunofluorescent and serological examinations. The disease was markedly generalized, however, with predominant involvement of the liver, lungs, and central nervous system of the type of pneumonia, hepatitis and encephalomyelitis. Early in the disease, changes of alveolocytes, hepatocytes, and other epitheliocytes were observed, consisting primarily in a peculiar alteration of their nuclei. Simultaneously, moderate signs of inflammation were observed, but in most severe cases it was alterative.

Studied was the effect of CCI4 intoxication of guinea pigs on the dynamics of changes taking place in the level of the total lipids and the esterificated and unesterificated fatty acids. It was found that following treatment with CCI4 the amount of the total lipids in the blood rose by the eighth hour and reached its peak value at the 24th hour. The unesterificated fatty acids rose considerably, while the esterificated ones showed but a slight rise. It is concluded on the basis of correlation coefficients that the changes in the level of the unesterificated fatty acids have the highest diagnostic value in the tetrachlormethane intoxication of the liver.

The paper deals with the results of the first phase of a WHO-sponsored study concerned with evaluation of the effectiveness of breast self-examination and carried out in Leningrad. The study was part of a program for early breast cancer diagnosis. 8,000 females were taught the procedure of self-examination. A randomized survey of a representative group of 400 females was conducted during the first 12 months using a special questionnaire. It was intended for evaluating the subjects' comprehension of the aims of the program, their attitude to it and their knowledge on cancer. Due to training as well as regular reminding, the percentage of women who practiced self-examination was as high as 75.1. The results of an analysis of refusals to carry out self-examination are presented.

Among respiratory syncytial (RS) viruses circulating in the territory of U.S.S.R., strain variations were observed based on the differences in activity of virus reproduction in human embryo kidney cell cultures at 39 degrees C and in virus sensitivity to antibodies. Mathematical expression of the correlation between these two genetic markers made it possible to classify the new isolates of RS virus into three groups differing in their virulence, namely high, mild and low virulent strains. Populations of RS virus strains varied depending on the epidemic season: during the first period (1976-1977) predominated the high virulent (52-78%) while during the second period (1977-1978) the mild virulent (55-65%) strains. The third period (1978-1979) was characterized by the circulation of a mixture of mild and low virulent strains. In summer low virulent virus strains prevailed (56-89%).

Forty placentas from patients affected with herpes simplex viruses of type I and II were studied by means of light and immunofluorescent microscopy, morphometry and serological investigation of fetal (infant) and mother's blood. Various morphological alterations in placenta were established. Some of them were specific and resulted from the effect of herpes virus on the cells (amniocytes, syncytiotrophoblast, decidual cells, vascular endothelium). The affected cells increased in size, herpes antigen was detected in their hyperchronic nuclei. Apart from this, in all placentas as well as in their vessels, moderate inflammatory response was observed. When antenatal death occurred, poor vascularization of villi was observed and specific alterations were most pronounced. When death occurred antenatally, alterations produced by herpes were rather moderate and acute alterations of placenta circulation predominated. In children born in a good condition, both specific and nonspecific alterations were insignificant and villi vascularization was good.

Piracetam and its 8 derivatives were studied in experiments on mice and rats with the use of standard neurotropic tests and nootropic activity tools. The electrophysiological index of GABA-ergic inhibition (the recovery cycle of cortical evoked potentials) was also investigated. It was shown that piracetam derivatives as well as piracetam itself have a pronounced antihypoxic activity and prevent the amnestic effect of electroshock in experimental passive avoidance. Most of them were inactive according to the standard neurotropic test. Piracetam derivatives with a hydrazide grouping in the side chain combine nootropic activity and a specific stimulant effect, while the derivatives possessing a phenyl ring combine nootropic and depressant activity.

To study the susceptibility of persons with different blood groups to influenza A, the presence of infection in a group of young children placed under constant observation for 6 years (1974-1980) and in a group of donors observed during 1979-1980 was studied in different epidemic situations. The susceptibility of the persons under observation to type A influenza viruses was shown to depend both on the blood group of the subjects and on the properties of circulating viruses. Persons with group B (III) blood were more susceptible to the virus at the period when new antigenic variants and serotypes appeared, persons with group O (I) blood were more susceptible to influenza infection at the period of the circulation of virulent strains, while persons with group A (II) blood were more susceptible at the period when less virulent strains circulated. The susceptibility of persons with different blood groups was found to change as changes in the properties of the strains occurred in the process of their circulation.

Studied was the dynamics of the changes taking place in the activity of a number of enzymes in the blood plasma (glutamate oxalacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), aldolase (ALD), creatine phosphokinase (CPK), guanase, and cholinesterase (CE). The calculation of the correlation coefficients and the regression lines revealed that GOT, GPT, LDH, ALD, and guanase raised their activity following treatment of the test animals up to a higher extent and at a higher rate. Lower rate changes were those in the activity of AP, leucinaminopeptidase, and CE. No changes whatever were found in the activity of CPK. On the basis of these results the diagnostic value is determined of both the individual enzymes and the enzyme constellation as a whole.

In application of mammography and aiming biopsy, synchronous carcinoma of contralateral breast may be detected in 2.4% of cases, on the average, 3 years earlier than by clinical examination only. Increased proliferation of contralateral breast tissue (a factor contributing to tumor development) is not a pathognomonic symptom since proliferation rate in ductal and lobular tissues decreases with age and in menopause. At least half metachronous carcinomas of the second breast should be considered synchronous ones overlooked in the course of primary treatment.

Respiratory syncytial (RS) virus strains isolated in different years varied by their antigenic and biological properties. The lowest degree of relatedness was found between the "street" virus and the prototype Long strain; the highest occured among the isolates from a given isolation period. Based on the mean indices of efficiency of the virus reproduction in human embryo lung (HEL) cells at 37 degrees C and 39 degrees C as well as on the degree of virus sensitivity to reference antibodies, the isolates from various years could be divided into three groups, namely high, mild and low virulent strains. The incidence of RS virus infections in children depended on the strain characteristic of virus population circulating in a community of children during the long-term observation period of 1976-1979. Cyclic variation was found in isolation rates of RS viruses; the duration of each cycle in different years ranged from 21 to 41 days. The variability of isolation cycles and the frequency of RS virus reinfections were closely related to the biological characteristics of circulating virus strains.