Muscle strength and bone density in patients with different rheumatic conditions: cross-sectional study

Aim

To explore the relationship between muscle strength and bone density in patients with different rheumatic diseases and to examine whether inflammatory arthritis was more harmful for muscle strength and bone loss than degenerative joint diseases.

Methods

The study included 361 men and women with a mean ± standard deviation age of 60.5 ± 11.4 years and different rheumatic conditions: regional syndromes, osteoarthritis of the hands, shoulders, knees, and hips, and inflammatory arthritis. Maximum voluntary back strength was measured by isometric dynamometry. Bone mineral density (BMD; g/cm²) of the lumbar spine, femoral neck, and distal radius was measured by dual-energy x-ray absorptiometry. Anthropometry and lifestyle characteristics were also assessed.

Results

Back strength was lowest in patients with hand and shoulder osteoarthritis (20.0 ± 17.9 kg), followed by patients with inflammatory arthritis (24.8 ± 19.2 kg). Patients with inflammatory arthritis had the lowest BMD at the mid-radius (0.650 ± 0.115 g/cm²) and femoral neck (0.873 ± 0.137 g/cm²), while patients with hand and shoulder osteoarthritis had the lowest BMD at the mid-radius (0.660 ± 0.101). In both sexes, muscle strength was significantly lower in patients who had lower BMD (T score<-1.0). Multiple regression analysis identified significant predictors of back strength to be spine BMD (P = 0.024) and body mass index (P = 0.004) in men and femoral neck BMD in women (P = 0.004).

Conclusion

Muscle strength decline may be connected to bone loss in patients with rheumatic conditions, especially those with inflammatory joint diseases.There is a concomitant decline in muscle strength of the upper and lower limbs and bone density after the fifth decade of the life (1,2). Impaired muscle function is a common consequence in patients with rheumatic diseases, especially those with inflammatory joint diseases. Muscle strength may also be significantly reduced around joints affected with osteoarthritis. Several studies showed greatly reduced isokinetic strength in patients with rheumatoid arthritis (3-5) and patients with knee osteoarthritis (6).It is also known that muscle strengthening can yield a bone-building effect (7). Exercises with greater loading and higher impact activities produce the greatest skeletal benefit (8). Increased muscle weakness can also compound the problem of low bone density by increasing the risk of falls and fracture. A positive correlation between muscle strength and bone density has been shown in several studies (9-17). Some of them demonstrated the association only in postmenopausal women (12,17) but not in men (9,13), while other found a site-specific correlation between muscle strength and bone mineral density (BMD) (4,12). However, several studies did not find a correlation between any measures of muscle strength and BMD (18,19). With such contradictory reports, it is difficult to make clinically relevant conclusions about the relationship between muscle strength and bone mass, although this may be one of the key factors that affect the rehabilitation outcome.The aim of the study was to assess the differences in muscle strength and bone density between patients with different rheumatic conditions. Since muscle strength is an important determinant of bone density, we explored whether the age-related decline in bone density and muscle strength was more pronounced in patients with inflammatory arthritis than in those with degenerative joint diseases.     

Application of microsatellite loci on the chromosome X for rapid prenatal detection of the chromosome X numerical abnormalities

Aim

To determine the value of short-tandem repeat markers on the chromosome X (X-STR) for prenatal diagnostics of the chromosome X numerical disorders.

Methods

We investigated the genetic variability of 5 X-markers (DXS9895, DXS6810, DXS6803, GATA172D05, and HPRTB) in 183 healthy Croatian individuals (90 men and 93 women). We also tested 13 patients with X chromosome disorders (Turner syndrome – 6 cases; Klinefelter syndrome – 5 cases, and Triple X syndrome – 2 cases). The analysis was performed using polymerase chain reaction amplification with specific primers and electrophoresis on a polyacrylamide gel. The study was performed in 2010.

Results

Our sample showed no significant differences in allelic frequencies of the investigated X-markers from other European populations. A set of 5 X-STR markers was sufficiently informative for a successful determination of the chromosome X numerical abnormalities.

Conclusion

Since no false positive or negative results were observed, diagnostic value of the investigated X-STR loci for prenatal detection of chromosome X numerical disorders was confirmed. Our study represents an important step toward an improved prenatal diagnostics in Croatia.The analysis of short tandem repeat (STR) markers using polymerase chain reaction (PCR) method has become a widely applied technique in forensic individual identification, rapid detection of chromosome aneuploidies in prenatal and postnatal diagnosis, as well as paternity testing (1-5). Until now, a large number of autosomal and Y-chromosomal markers has been forensically evaluated and used for various purposes. Although X-chromosomal markers have been increasingly applied in both forensic and medical field, their role has not been as extensively investigated as that of autosomal and Y-chromosomal markers. Several investigations have documented the accuracy of fluorescent PCR using STR loci for the rapid prenatal diagnoses of numerical disorders affecting the chromosomes 21, 18, and 13 (6-8). However, the low polymorphism of the most chromosome X and Y markers has hampered the use of the PCR-STR approach for the detection of numerical disorders of sex chromosomes, such as the Turner (45, X) or Klinefelter (47, XXY) syndromes (1,7). A few years ago, a group of authors reported on the application of PCR-STR method in the detection of X-chromosome abnormalities (9,10). One of the biggest challenges is the Turner syndrome, in which a sufficient number of STR loci has to be included to be sure that the individual has only a single X chromosome. The aims of the present study were to investigate the diagnostic informativeness of 5 X-linked STR markers: DXS9895 (Xpter-Xp22.1), GATA172D05 (Xq26.1), DXS6810 (Xq12-Xq21.33), DXS6803 (Xq24-Xq27), and HPRTB (Xq27.3) in the Croatian population and to evaluate the diagnostic value of these 5 loci.     

Urban-rural differences in a population-based breast cancer screening program in Croatia

Aim

To investigate urban-rural differences in the distribution of risk factors for breast cancer.

Methods

We analyzed the data from the first round of the “Mamma” population based-screening program conducted in Croatia between 2007 and 2009 and self-reported questionnaire results for 924 patients with histologically verified breast cancer. Reproductive and anthropometric characteristics, family history of breast cancer, history of breast disease, and prior breast screening history were compared between participants from the city of Zagreb (n = 270) and participants from 13 counties with more than 50% of rural inhabitants (n = 654).

Results

The screen-detected breast cancer rate was 4.5 per 1000 mammographies in rural counties and 4.6 in the city of Zagreb, while the participation rate was 61% in rural counties and 59% in Zagreb. Women from Zagreb had significantly more characteristics associated with an increased risk of breast cancer (P < 0.001 in all cases): no pregnancies (15% vs 7%), late age of first pregnancy (≥30 years) (10% vs 4%), and the most recent mammogram conducted 2-3 years ago (32% vs 14%). Women from rural counties were more often obese (41% vs 28%) and had early age of first live birth (<20 years) (20% vs 7%, P < 0.001 for both).

Conclusion

Identification of rural-urban differences in mammography use and their causes at the population level can be useful in designing and implementing interventions targeted at the reduction of inequalities and modifiable risk factors.Significant differences in breast cancer frequency have been identified in different socioeconomic groups, ethnic groups, and between urban and rural populations (1,2). Living in rural areas may be associated with lower access to health care and mammography screening (3), as well as with late-stage diagnosis (4). This often means that patients need to travel great distances to receive care (5). Blair et al found that people in rural and urban areas were diagnosed with breast cancer at similar stages of the disease, although those from rural communities lacked basic cancer information because they did not have access to cancer education programs offered in urban areas (6). Robbins et al explained the higher breast cancer incidence in the San Francisco Bay Area than in other regions by known risk factors: parity, age at first full-term pregnancy, breast-feeding, age at menarche, and age at menopause (7). In Croatia, Polašek et al found that in a period without a national cancer screening program access to health care was the strongest cancer screening utilization predictor in adult rural population (8).Risk factors for breast cancer are mostly those related to the reproductive life of women (9,10): menarche, nulliparity or late age at first birth, late menopause, as well as hormonal factors, be they endogenous or exogenous (eg, term use of oral contraceptives or menopausal hormonal replacement). Other risk factors related to hormonal status include obesity and a diet characterized by a high caloric intake, low intake of fruits and vegetables, and lack of physical activity (11). Radiation, in particular during breast development, was also found to be a risk factor (12), while the role of contaminants, such as xenoestrogens and certain pesticides, remains controversial. Four- to 5-fold risk of developing breast cancer was associated with epithelial proliferative lesions, particularly atypical ductal or lobular hyperplasia (11).In Croatia, breast cancer is the leading cancer among women, amounting to 27% of new female cancer cases; moreover, the incidence rate in 2007 was 17% higher than in the previous year (13). In 2007, cancer incidence by county and age-standardized rates per 100 000 women varied considerably: from 273.1 (Šibensko-kninska county) to 437.7 (the city of Zagreb), but the prevalence of breast cancer risk factors remains unknown. A government-funded mammography screening program was established in October 2006 and has since been implemented in 21 counties, including the city of Zagreb (14).Population-based screening for breast cancer is conducted through mammographic examination of all women of a specified age at prescribed time intervals. The implementation of population-based screening requires technical resources and trained personnel for double reading of mammograms, as well as a major media campaign (15).Within a more extensive study of breast cancer risk factors, this study investigated urban-rural differences in reproductive, anthropometric, and family history of breast cancer and personal history of breast disease among women aged 50-69 from 13 rural counties and the city of Zagreb who participated in the first round of population-based mammography screening in Croatia.     

Forensic DNA databases in Western Balkan region: retrospectives, perspectives, and initiatives

The European Network of Forensic Science Institutes (ENFSI) recommended the establishment of forensic DNA databases and specific implementation and management legislations for all EU/ENFSI members. Therefore, forensic institutions from Bosnia and Herzegovina, Serbia, Montenegro, and Macedonia launched a wide set of activities to support these recommendations. To assess the current state, a regional expert team completed detailed screening and investigation of the existing forensic DNA data repositories and associated legislation in these countries. The scope also included relevant concurrent projects and a wide spectrum of different activities in relation to forensics DNA use. The state of forensic DNA analysis was also determined in the neighboring Slovenia and Croatia, which already have functional national DNA databases. There is a need for a 'regional supplement' to the current documentation and standards pertaining to forensic application of DNA databases, which should include regional-specific preliminary aims and recommendations.     

Cancer epidemiology in Central, South and Eastern European countries

Aim

To collect cancer epidemiology data in South Eastern European countries as a basis for potential comparison of their performance in cancer care.

Methods

The South Eastern European Research Oncology Group (SEEROG) collected and analyzed epidemiological data on incidence and mortality that reflect cancer management in 8 countries – Croatia, Czech Republic, Hungary, Romania, Poland, Slovakia, and Serbia and Montenegro in the last 20-40 years.

Results

The most common cancer type in men in all countries was lung cancer, followed by colorectal and prostate cancer, with the exception of the Czech Republic, where prostate cancer and colorectal cancer were more common. The most frequent cancer in women was breast cancer followed by colorectal cancer, with the exceptions of Romania and Central Serbia where cervical cancer was the second most common. Cancer mortality data from the last 20-40 years revealed two different patterns in men. In Romania and in Serbia and Montenegro, there was a trend toward an increase, while in the other countries mortality was declining, after increasing for a number of years. In women, a steady decline was observed over many years in the Czech Republic, Hungary, and Slovakia, while in the other countries it remained unchanged.

Conclusions

There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors which provides a clear challenge to prevention. There are some differences in incidence and mortality that cannot be explained by exposure to known risk factors or treatment availabilities.On a global scale, cancer has become a major public health problem and an increasingly important contributor to the burden of disease. Based on the most recent available international data, there were an estimated 12.7 million new cancer cases, 7.6 million deaths from cancer, and 28 million persons alive with cancer within five years from the initial diagnosis (1-3). The most common cancers in the world were lung (1.61 million cases), breast (1.38 million), and colorectal cancer (1.24 million) (3). Because of its poor prognosis, lung cancer was also the most common cause of death (1.38 million), followed by gastric (737 000 deaths), and liver cancer (695 000 deaths) (1-4).Priority setting for cancer control and cancer services in any region needs to be based on knowledge of the cancer burden and the local mix of predominant cancer types (5). According to estimates of global cancer burden made by the International Agency for Research on Cancer (IARC), the incidence and mortality rates from many specific types of cancer and all cancers combined vary widely by geographic locality (6). Moreover, the IARC also estimated that over half of newly diagnosed cases and two-thirds of cancer deaths occur in low and medium-income countries (6). There are striking variations in the pattern of cancer by site from region to region (7). The large differences in incidence and mortality in different countries may reflect a combination of differences in prevalence of underlying risk factors, differences in host susceptibility, and/or variations in cancer detection, reporting, classification systems, treatment, and follow-up. Among European countries, wide differences in the quality of cancer care are observed, especially when comparison is made between “old” and “new” EU members or between developed and developing countries (8). Cancer survival is significantly lower in Eastern European countries, including the new Member States, than in the EU 15 (9-12). Transitional countries and middle income countries are frequently left forgotten “in between” and the cancer problem in these countries is among the worst and fastest growing (8).In this report, we provide an analysis, which we propose as a foundation for detailed evaluation of cancer care in selected Central, Southern and Eastern European countries, represented by members of the South Eastern European Research Oncology Group (SEEROG). Our epidemiological analysis indicates the scale of the problem of oncological care in individual countries and shows current trends in the incidence of particular cancers. Comparison of status of oncology between countries in Eastern, Southern, and Central European region has never been undertaken before and key barriers to deliver appropriate quality of care have not previously been identified.     

Autonomic mechanisms underpinning the stress response in borderline hypertensive rats

This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors.     

Status of tobacco viruses in Serbia and molecular characterization of tomato spotted wilt virus isolates

In a four-year survey to determine the presence and distribution of viruses in tobacco crops at 17 localities of the Vojvodina Province and Central Serbia, 380 samples were collected and analyzed by DAS-ELISA. Out of the seven viruses tested, tomato spotted wilt virus (TSWV), potato virus Y (PVY), tobacco mosaic virus (TMV), cucumber mosaic virus (CMV), and alfalfa mosaic virus (AMV) were detected in 37.9, 33.4, 28.7, 23.9, and 15.5% of the total tested samples, respectively. TSWV was the most frequently found virus at the localities of Central Serbia, while PVY and CMV were the most frequent viruses in the Vojvodina Province. Single infections were prevalent in years 2005-2007 and the most frequent were those of PVY. A triple combination of those viruses was most frequent mixed infection type in 2008. The presence of all five detected viruses was confirmed in selected ELISA-positive samples by RT-PCR and sequencing. The comparisons of obtained virus isolate sequences with those available in NCBI, confirmed the authenticity of serologically detected viruses. Phylogenetic analysis based on partial nucleocapsid gene sequences revealed a joint clustering of Serbian, Bulgarian and Montenegrin TSWV isolates into one geographic subpopulation, which was distinct from the other subpopulation of TSWV isolates from the rest of the European countries. The high incidence of viruses in Serbian tobacco crops highlights the importance of enhancing farmers knowledge towards better implementation of control strategies for preventing serious losses.     

Evaluation of the effect of myocardial segmentation errors on myocardial blood flow estimates from DCE-MRI

Quantitative analysis of cardiac dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) perfusion datasets is dependent on the drawing (manually or automatically) of myocardial contours. The required accuracy of these contours for myocardial blood flow (MBF) estimation is not well understood. This study investigates the relationship between myocardial contour errors and MBF errors. Myocardial contours were manually drawn on DCE-MRI perfusion datasets of healthy volunteers imaged in systole. Systematic and random contour errors were simulated using spline curves and the resulting errors in MBF were calculated. The degree of contour error was also evaluated by two recognized segmentation metrics. We derived contour error tolerances in terms of the maximum deviation (MD) a contour could deviate radially from the 'true' contour expressed as a fraction of each volunteer's mean myocardial width (MW). Significant MBF errors were avoided by setting tolerances of MD ≤ 0.4?MW, when considering the whole myocardium, MD ≤ 0.3?MW, when considering six radial segments, and MD ≤ 0.2?MW for further subdivision into endo- and epicardial regions, with the exception of the anteroseptal region, which required greater accuracy. None of the considered segmentation metrics correlated with MBF error; thus, both segmentation metrics and MBF errors should be used to evaluate contouring algorithms.