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Histological observations on Montenegro's reaction in man.

The Montenegro skin test is widely used as a diagnostic method for American cutaneous leishmaniasis (ACL) but little is known about the histological changes that occur in the skin after administration of the antigen. This report is based on histological studies of biopsied material obtained, from inoculation sites, 48 hours after individuals had been given intradermal injections with a standardized Montenegro antigen. The material examined was obtained from four distinctly different test groups: naturally infected patients with parasitologically proved ACL and with positive Montenegro's reaction; individuals without previous history of ACL and not previously tested with Montenegro antigen; participants in anti-ACL vaccine trials who developed positive reactions to Montenegro antigen after vaccination; other participants in vaccine trials who had negative Montenegro responses after vaccination or had served as controls in the trials. The histological pictures of each group are described and discussed. Histologically, the reactions of vaccinated individuals were indistinguishable from those with naturally acquired infections.

Humans↗

[Total atmospheric ozone column above the territory of Serbia and Montenegro].

INTRODUCTION: Atmospheric ozone attenuates ultraviolet radiation reaching the Earth's surface. Since UV-B radiation is considered the principal factor of causing the skin cancers, cataracts and some immunological disorders, determination of total ozone column has become everyday practice. In Serbia and Montenegro, such determinations are not being done. Satellite data for the entire globe are accessible. OBJECTIVE: The objective of our work was to collect and analyze data for the territory of Serbia and Montenegro, because ozone is an important parameter for the study of effects and protection from UV radiation. METHODS: Data collected during TOMS (Total Ozone Measuring Spectrometer) experiment are presented for grid whose elements are 1 degrees latitude by 1.25 degrees longitude. Grid elements in which the territory of Serbia and Montenegro comprises more than 50% of the element area were taken to represent the territory of Serbia and Montenegro. Eleven grid elements were selected and average monthly values for 272 months in the period from 1978 until 2004 were collected. Data for the period between 1993 and 1996 were unavailable. RESULTS: Mean values of total ozone column and mean monthly values of eleven grid elements differed very little. Differences were smaller than magnitudes of random error. Average annual values of total ozone column above the territory of Serbia and Montenegro were in the range from 316 Dobson units (DU) in 2002 to 347 DU in 1981. Annual cyclic changes of total ozone column showed spring maxima and autumn minima. Maximal recorded monthly value was 421 DU in March 1987 and minimal monthly value was 271 DU in October 2001. There was a trend of decreasing total ozone column values in the period between 1979 and 1992 at the rate of approximately 4.5% per decade. CONCLUSION: Mean total ozone column value above the territory of Serbia and Montenegro can represent total ozone column for the whole territory. Annual cycles with spring maxima and autumn minima are in accordance with oscillations observed for middle northern latitudes. The trend showing 4.5% decrease per decade in the period between 1979 and 1992 corresponds well to trends calculated for comparable locations.

Atmosphere↗

Concentration and characteristics of depleted uranium in water, air and biological samples collected in Serbia and Montenegro.

During the Balkan conflicts, in 1995 and 1999, depleted uranium (DU) rounds were employed and were left in the battlefield. Health concern is related to the risk arising from contamination of the environment with DU penetrators and dust. In order to evaluate the impact of DU on the environment and population in Serbia and Montenegro, radiological surveys of DU in water, air and biological samples were carried out over the period 27 October-5 November 2001. The uranium isotopic concentrations in biological samples collected in Serbia and Montenegro, mainly lichens and barks, were found to be in the range of 0.67-704 Bqkg(-1) for (238)U, 0.48-93.9 Bqkg(-1) for (234)U and 0.02-12.2 Bqkg(-1) for (235)U, showing uranium levels to be higher than in the samples collected at the control sites. Moreover, (236)U was detectable in some of the samples. The isotopic ratios of (234)U/(238)U showed DU to be detectable in many biological samples at all examined sites, especially in Montenegro, indicating widespread ground-surface DU contamination, albeit at very low level. The uranium isotopic concentrations in air obtained from the air filter samples collected in Serbia and Montenegro were found to be in the range of 1.99-42.1 microBqm(-3) for (238)U, 0.96-38.0 microBqm(-3) for (234)U, and 0.05-1.83 microBqm(-3) for (235)U, being in the typical range of natural uranium values. Thus said, most of the air samples are DU positive, this fact agreeing well with the widespread DU contamination detected in the biological samples. The uranium concentrations in water samples collected in Serbia and Montenegro were found to be in the range of 0.40-21.9 mBql(-1) for (238)U, 0.27-28.1 mBql(-1) for (234)U, and 0.01-0.88 mBql(-1) for (235)U, these values being much lower than those in mineral water found in central Italy and below the WHO guideline for drinking water. From a radiotoxicological point of view, at this moment there is no significant radiological risk related to these investigated sites in terms of possible DU contamination of water, air and/or plants.

Air Pollutants, Radioactive↗

Induction and modulation of the immune response to Leishmania by Montenegro's skin test.

The intradermal inoculation in naive or in previously sensitized individuals of small amounts of Leishmania extract (Montenegro's skin test) induced or modulated, respectively, the immune response to Leishmania, as assessed by subsequent Montenegro's skin tests. These phenomena could hinder the interpretation of Montenegro's skin tests in a population already subjected to the test in the past and, in addition, could affect in an unknown way the development of mucosal lesions in people infected with L. braziliensis or L. amazonensis, since those lesions have been associated with hypersensitivity to Leishmania antigens. Anti-Leishmania antibody responses, assessed by enzyme-linked immunosorbent assay, were not induced in naive individuals by Montenegro's skin tests, but tended to become more intense following these tests in previously sensitized individuals.

Animals↗

The pattern of lung cancer mortality in Montenegro.

The aim of the study was to examine recent lung cancer mortality trends in Montenegro in the period 1976-2000, with special emphasis on correlation with tobacco consumption. A population-based study analysing lung cancer mortality in Montenegro in the period 1976-2000 was carried out. Mortality rates were adjusted by direct method. A cohort analysis of age-specific death rates was performed. The analysis of tobacco consumption (cigarettes consumption per capita) was based on the official data for the period 1965-1990. Linear regression coefficients in a time trends analysis of mortality rates and tobacco consumption were assessed using Fisher's test. The highest average standardized lung cancer mortality rates in Montenegro increased in each successive five-year period for both sexes from 1976 to 2000, with highest values in the last five years (1996-2000). In males the death rate has almost doubled, and in females it was nearly three-fold higher. In the cohort analysis of age-specific death rates, all age groups in the birth cohort born before 1911 had a higher lung cancer mortality risk than those in the birth cohort comprising those born between 1912 and 1931. The rates showed an increasing tendency in all age groups irrespective of sex, except in males in the 25-44 age group. The time analysis of lung cancer mortality rates for the period 1976-2000, revealed annual changes of 3% for males and 6.6% for females, respectively. During the period observed the consumption of cigarettes increased by 98.2% (from 1.064 kg per capita in 1965 to 2.109 kg per capita in 1990). The significant increasing tendency in cigarette consumption was registered (y=1.10+0.05x, P=0.001). A significant correlation between lung cancer mortality rates and cigarette consumption is also observed (r=0.427, P=0.037). Smoking trends up to the 1990s in Montenegro, indicate that one can expect lung cancer mortality rates to continue to increase in males but even more so in females.

Adolescent↗

JP-3 gene polymorphism in a healthy population of Serbia and Montenegro.

Expansions of CTG repeats in JP-3 gene are associated with a phenotype similar to Huntington disease. These expansions are the cause of Huntington disease like-2 (HDL-2) phenotype. CTG repeats in JP-3 gene are polymorphic in healthy population. Analyses of CTG repeat polymorphism of JP-3 gene in various healthy populations could help in estimating the population at risk for developing HDL-2. CTG repeat polymorphism of JP-3 gene was analysed in healthy population of Serbia and Montenegro. Study included 198 unrelated subjects. Analyses of JP-3 locus were performed using PCR and sequencing. Six different JP-3 alleles were obtained and they were in the range of 11 to 18 CTG repeats showing a bimodal distribution, with peaks at 14 and 16. Results show that the distribution of JP-3 alleles in population of Serbia and Montenegro is consistent with distributions in other analysed populations. The absence of alleles with more then 18 CTG repeats suggests that HDL-2 is very rare in the populations of Serbia and Montenegro.

Female↗

[Evaluation of the sensitization power of Montenegro skin test].

The Montenegro skin test, used to diagnose cutaneous leishmaniasis, is now being considered to detect immunogenicity after vaccination. In this study, we evaluated the ability of this test to induce immune response and IFN-g production in subjects not previously exposed to Leishmania. The Montenegro skin test was performed using antigens of L. amazonensis produced by our laboratory (group I) or by FIOCRU-RJ (group II). At day 30, 33% of the subjects from group I and 42% from group II were positive, compared to 67% from group I and 50% from group II at day 90. IFN-y was detected in 56 % of subjects from group I and 17% from group II at day 30 (169+/-309 and 11+/-36pg/ml) and in 67% from group I and 58% from group II by day 360 (69+/-107 and 18+/-20pg/ml). These data demonstrate that the Montenegro skin test induces not only a delayed hypersensitivity reaction, but also IFN-y production.

Adolescent↗

[Divna Veković (1886-1944)--the first woman physician in Montenegro].

The authors are dealing with historical and political situation in Montenegro in the second part of the 19th century. They emphasized the importance of foundation of the Empress Maria Girls' Institute, which was financed by the Empress of Russia. Many famous South-Slav intellectuals have graduated from this Institute. Among them, the name of Divna Veković, the first woman physician in Montenegro, particularly stands out. A Sorbonne student, she was an outstanding physician and humanitarian during the First World War. Between the two World Wars, she revealed the spiritual wealth of Montenegro to Europe. She was the first to translate the Mountain of Wreath into French. She also translated the poetry of J. J. Zmaj and of other poets. During the World War II she continued her work in her birth place. She cared for the sick, the wounded and the poor. She died at the end of the war under mysterious circumstances. In the history of Montenegrin medicine, she has almost been forgotten. The aim of this paper is to lift the veil of oblivion from the life and work of this noble woman.

Female↗

[The role of central registry in control and research of sarcoidosls in Serbia and Montenegro].

INTRODUCTION: The incidence of sarcoidosis varies according to ethnic origin, geographic region and genetic factors. It might be more prevalent than reported Serbia & Montenegro is a Balkan country which has a population of about 8 million inhabitants and occupies part of the territory of ex-Yugoslavia. Epidemiological data on sarcoidosis are collected and followed-up through a network of referral facilities. The aim of the study was to analyze some sarcoidosis epidemiological features in Serbia&Montenegro in a 10-year period (1991-2002) and to highlight advantages of central sarcoidosis register. MATERIAL AND METHODS: Annual reports of two referral institutions (one from Serbia, the other from Montenegro) on sarcoidosis were analyzed, as well as official mortality statistics. RESULTS: The incidence rate (IR) trend for sarcoidosis is stable with 1.9/100,000 inhabitants on average in 12 year period (RR: 1.3 - 2.6%). In the last year of the analyzed period--2002--IR was 1.3/100,000 pop. IR varies significantly by region (0.05 - 4.9/100,000). Female to male ratio is 1.84. The prevalence of sarcoidosis has an increasing tendency and might require precise exclusion criteria of cases in registries. The mortality rate is below 1/100,000 both in females and males. CONCLUSION: Although we assume that provided data are accurate on average, a central sarcoidosis registry would improve registration, follow-up and research on sarcoidosis. Significant IR differences among regions might be an object of another investigation, as well as a study of genetic predispositions to sarcoidosis.

Female↗

[Results of Montenegro's reaction in patients with mucocutaneous leishmaniasis, from Espírito Santo state].

The authors analysed the results of Montenegro Test in 402 patients with mucocutaneous leishmaniasis from Espírito Santo State, where the Leishmania braziliensis braziliensis has been isolated from humans cases and dogs. The test was positive in 371 cases (92.2%) before treatment. The Montenegro Test given during or after treatment changed the results in 17 of 20 negative cases. The remaining 3 cases and 9 which changed the results had positives biopsies. It was demonstrated again the efficiency of the Montenegro Test in the diagnosis of mucocutaneous leishmaniasis.

Adolescent↗

Trends in consumption of psychiatric drugs in Serbia and Montenegro 2000-2004.

PURPOSE: To investigate the trends in psychiatric drugs utilization in Serbia and Montenegro over the 5-years period (2000-2004). MATERIALS AND METHODS: The wholesale data issued by the manufacturers or distributors were used. Also, the lists of drugs used from the Institute of Mental Health (institution which provides primary, secondary and tertiary psychiatric care) were used to corroborate the wholesale data. The utilization of drugs in general population was calculated using ATC/DDD methodology, and was expressed in Defined Daily Doses (DDD) per 1000 inhabitants per day. The utilization of drugs in the Institute of Mental Health was calculated from the hospital pharmacy records and was expressed as the number of DDDs per 100 bed-days. The statistics was performed using standard statistical methods. RESULTS: The general consumption of psychiatric drugs in Serbia and Montenegro significantly increased during the 2000-2004 period (from 45.1 DDD/1000 inhabitants/day in 2000 to 69.1 DDD/1000 inhour/day in 2004). The general utilization of anxiolytic/hypnotic drugs surged significantly, but the inhospital use remained rather stable. The most prominent changes were noted in the utilization of antidepressants, which doubled in that period, both in general and inhospital settings. Among antipsychotics in general population, there is a significant increase in the utilization of clozapine. In inhospital setting, there is a significant increase of total utilization of antipsychotic drugs, but this is also mainly on the account of atypicals. CONCLUSIONS: The total consumption of psychiatric drugs significantly increased. The utilization of anxiolytic/hypnotic drugs in 2004 reached 60 DDDs/1000 inhabitants/day, which is in collision with the trend in developed countries. It is necessary to form national guidelines for prescribing anxiolytic/hypnotic drugs, in order to rationalize their use. More favourable is the antidepressant (SSRIs in particular) and atypical antipsychotic drugs utilization increase.

Developing Countries↗

Montenegro skin tests for American cutaneous leishmaniasis carried out on school children in Rio de Janeiro, Brazil: an indicator of transmission risk.

Montenegro skin tests were carried out in 1985 and 1987 on two groups of school children in the city of Rio de Janeiro. Group A consisted of 449 children residing in the Jacarepagua district, in areas where transmission of human and canine American cutaneous leishmaniasis (ACL) has been high; this group was considered to be the one at greatest risk of acquiring the infection through L. braziliensis. Group B consisted of 282 children from Bonsucesso, a suburb of Rio de Janeiro that is at a considerable distance from any area where ACL is endemic; this was a lowest risk group, and was thus used as a control. Analysis of the cutaneous test results showed that in Group A, 8.9% of the sample tested positive, whereas in Group B the result was only 2.1%. In group A there were no significant differences in the proportion of positives when analysed according to sex, age and the year when the tests were carried out. A study of the effects associated with place of residence together with other variables was carried out using log-linear regression analysis. It showed that effects arising from place of residence were maintained; that this was the only significant effect; and that it was independent of other variables. The testing of school children using the Montenegro intradermal test was shown to be a useful procedure in the characterization of localities in which there is a risk of ACL infection.

Adolescent↗

Skin reactivity to thimerosal and phenol-preserved Montenegro antigen in Brazil.

A randomized double-blind trial was performed to determine the frequency of positive reactions to the Montenegro antigen (leishmanin) preserved in thimerosal (Merthiolate) 1:10,000 or phenol 0.4%. The respective products were tested separately in 400 young healthy individuals from a non-endemic area for Leishmaniases. Each volunteer received one of the following reagents: merthiolated antigen, phenolated antigen, merthiolated saline, or phenolated saline. The frequency of positive responses to each reagent after the first application was as follows: 0% (phenolated saline), 9.2% (merthiolated saline), 34.6% (antigen in phenolated saline), and 41.1% (antigen in merthiolated saline). After 1 week, volunteers who had tested positive for merthiolated or phenolated antigen were retested with the respective preservative, while negatives were retested with the preservative they had not received during the first test. In all, 331 volunteers who received merthiolated saline during the study, of whom 41 (12.4%) tested positive. Meanwhile, 326 volunteers who received phenolated saline, 4 (1.2%) tested positive. Positive reactions in each group were similar in relation to gross appearance skin reactions. Considering the high frequency of hypersensitivity to thimerosal in the study population, it is recommended that this compound should be replaced as a preservative of the leishmanin antigen. Almost 30% of positive reactions to Montenegro antigen in what is considered a non-endemic region was surprising and will be the object of future studies.

Adolescent↗

Human Y-specific STR haplotypes in population of Serbia and Montenegro.

Nine Y chromosome short tandem repeat (STR) loci (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393) were analyzed in group of 237 unrelated healthy males from population of Serbia and Montenegro in order to assess the frequencies of Y haplotypes. We observed 174 different haplotypes of which 146 (61.6%) were seen only once. Y-STR allelic frequencies in Serbia and Montenegro, in general, correspond to other European populations, except for the DYS19, DYS385 and DYS389II loci.

Chromosomes, Human, Y↗

Montenegro's skin reactions and antibodies against different Leishmania species in dogs from a visceral leishmaniosis endemic area.

In this study, humoral (circulating anti-Leishmania antibodies) and cellular (Montenegro's skin test) immune responses of dogs from an endemic area of visceral leishmaniosis were tested using Leishmania chagasi, Leishmania amazonensis and Leishmania braziliensis antigens. The antibody response was tested in three animal groups, selected according to their anti-L. chagasi antibody activity, as measured by ELISA in the serum: 19 negative (O.D. below 0.30), seven with undefined (O.D. between 0.40 and 0.70) and 12 positive (O.D. above 1.0) ELISA result. In the group of animals with positive ELISA, the antibody activity against L. chagasi antigens (mean O.D.=1.31) was significantly higher (ANOVA, P<0.01) than against L. amazonensis (mean O.D.=0.88) or L. braziliensis (mean O.D.=0.87) antigens. The Montenegro's skin test results obtained with L. chagasi and L. braziliensis antigens showed a fair agreement (kappa=0.309). The same was observed when antigens from L. braziliensis and L. amazonensis were compared (kappa=0.374), whereas a moderate agreement between the results from tests performed with L. chagasi and L. amazonensis antigens was observed (kappa=0.530). The induration areas obtained with L. braziliensis antigen were smaller than those obtained with the other antigens. The data presented herein indicate that the use of antigens from different Leishmania species may interfere with the results of the immunological tests performed in dogs in an endemic area of visceral leishmaniosis.

Analysis of Variance↗

Anti-CagA and anti-VacA antibodies in Helicobacter pylori-infected patients with and without peptic ulcer disease in Serbia and Montenegro.

BACKGROUND: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori-positive dyspeptic patients in Serbia and Montenegro. METHODS: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49 +/- 15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti-IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non-ulcer dyspepsia (NUD) in the remaining 142 patients. RESULTS: 129 (74.6%) patients were H. pylori-positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P < 0.01); 121 (93.8%) patients carried anti-CagA antibodies and there was no difference between the DU and NUD groups. VacA antibodies were detected in sera of 50 (38.75%) and were more prevalent in patients with DU compared to the NUD group (P < 0.05). CONCLUSIONS: In Serbia and Montenegro there is high seroprevalence of CagA-positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA-positive strains are more closely related to peptic ulcer disease.

Adult↗

The Balkan Piedmont: male suicide rates pre-war, wartime, and post-war in Serbia and Montenegro.

The epidemiology of suicide in Serbia and Montenegro from 1989 to 2003, a period of civil war, is presented. Following the break-up of former Yugoslavia, Serbia and Montenegro underwent a period of war from 1991-1994 and another in 1999. During the war years, the number of suicides increased, reaching its peak in 1993. Male suicides outnumbered female suicides by a ratio of 2:1. Male suicides decreased slightly after the war of 1991-1994 only to rise in 1997 and continue at this higher level throughout the nineties. In Serbia alone, male suicide reached its peak in 2002 (nearly 29/100,000). The methods of suicide changed significantly, with the use of firearms doubling during and after the war years. Speculations are offered about the findings, many consistent with Durkheim's classical hypothesis concerning suicide and unpopular wars.

Demography↗

Analysis of thiopurine S-methyltransferase polymorphism in the population of Serbia and Montenegro and mercaptopurine therapy tolerance in childhood acute lymphoblastic leukemia.

Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. It is now well established that interindividual variation in sensitivity to thiopurines can be the result of the presence of genetic polymorphisms in the TPMT gene. The aim of this study was to determine the frequency and type of TPMT polymorphisms in the population of Serbia and Montenegro and to assess its relevance in the management of childhood acute lymphoblastic leukemia (ALL). Blood samples from 100 healthy adults and 100 children with ALL were analyzed for common mutations in the TPMT gene using polymerase chain reaction-based assays. The results revealed that allelic frequencies were 0.2% for TPMT*2, 3.2% for TPMT*3A, and 0.5% for TPMT*3B. A rare TPMT*3B allele was detected in 2 families. No TPMT*3C allele was found. The general pattern of TPMT-variant allele distribution as well as their frequencies in the population of Serbia and Montenegro, is similar to those determined for other Slavic and Mediterranean populations. The ability to tolerate 6-mercaptopurine (6-MP) -based maintenance therapy was used as a surrogate marker of hematologic toxicity. In the study of 50 patients with childhood ALL treated according to the BFM-like protocol, it was found that even TPMT-heterozygous patients are at greater risk of thiopurine drug-related leukopenia (mean duration of period when children missed therapy as a result of leukopenia for TPMT-heterozygous patients was 11.3 weeks vs 3.4 weeks for wild-type genotype patients, P < 0.01). In another group of 50 patients, the TPMT genotype was determined prospectively. The therapy protocol was modified considering their TPMT genotype. Administering reduced 6-MP dosages in the initial phase of maintenance allowed TPMT-heterozygous patients to later receive full protocol doses of both 6-MP and nonthiopurine therapy without omitting therapy resulting from myelotoxicity. These results justify performing TPMT genotyping before initiating thiopurine therapy in all children with ALL to minimize consequent toxicity.

Child↗