OCCUPATIONAL DOSE ASSESSMENT IN INTERVENTIONAL CARDIOLOGY IN SERBIA.

The objective of this work is to assess the occupational dose in interventional cardiology in a large hospital in Belgrade, Serbia. A double-dosimetry method was applied for the estimation of whole-body dose, using thermoluminescent dosemeters, calibrated in terms of the personal dose equivalent Hp(10). Besides the double-dosimetry method, eye dose was also estimated by means of measuring ambient dose equivalent, H*(10), and doses per procedure were reported. Doses were assessed for 13 physicians, 6 nurses and 10 radiographers, for 2 consequent years. The maximum annual effective dose assessed was 4.3, 2.1 and 1.3 mSv for physicians, nurses and radiographers, respectively. The maximum doses recorded by the dosemeter worn at the collar level (over the apron) were 16.8, 11.9 and 4.5 mSv, respectively. This value was used for the eye lens dose assessment. Estimated doses are in accordance with or higher than annual dose limits for the occupational exposure.

Radiation exposure to nuclear medicine staff involved in PET/CT practice in Serbia.

The purpose of this work is to evaluate the radiation exposure to nuclear medicine (NM) staff in the two positron emission tomography-computed tomography centres in Serbia and to investigate the possibilities for dose reduction. Dose levels in terms of Hp(10) for whole body and Hp(0.07) for hands of NM staff were assessed using thermoluminescence and electronic personal dosemeters. The assessed doses per procedure in terms of Hp(10) were 4.2-7 and 5-6 µSv, in two centres, respectively, whereas the extremity doses in terms of Hp(0.07) in one of the centres was 34-126 µSv procedure(-1). The whole-body doses per unit activity were 17-19 and 21-26 µSv GBq(-1) in two centres, respectively, and the normalised finger dose in one centre was 170-680 µSv GBq(-1). The maximal estimated annual whole-body doses in two centres were 3.4 and 2.0 mSv, while the corresponding extremity dose in the later one was 45 mSv. Improvements as introduction of automatic dispensing system and injection and optimisation of working practice resulted in dose reduction ranging from 12 up to 67 %.

Eye lens dosimetry in interventional cardiology: results of staff dose measurements and link to patient dose levels.

Workers involved in interventional cardiology procedures receive high eye lens dose if protection is not used. Currently, there is no suitable method for routine use for the measurement of eye dose. Since most angiography machines are equipped with suitable patient dosemeters, deriving factors linking staff eye doses to the patient doses can be helpful. In this study the patient kerma-area product, cumulative dose at an interventional reference point and eye dose in terms of Hp(3) of the cardiologists, nurses and radiographers for interventional cardiology procedures have been measured. Correlations between the patient dose and the staff eye dose were obtained. The mean eye dose was 121 µSv for the first operator, 33 µSv for the second operator/nurse and 12 µSv for radiographer. Normalised eye lens doses per unit kerma-area product were 0.94 µSv Gy⁻¹ cm⁻² for the first operator, 0.33 µSv Gy⁻¹ cm⁻² for the second operator/nurse and 0.16 µSv Gy⁻¹ cm⁻² for radiographers. Statistical analysis indicated that there is a weak but significant (p < 0.01) correlation between the eye dose and the kerma-area product for all three staff categories. These values are based on a local practice and may provide useful reference for other studies for validation and for wider utilisation in assessing the eye dose using patient dose values.

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases.

In humans and most animal models, the development of obesity leads not only to increased fat depots in classical adipose tissue locations but also to significant lipid deposits within and around other tissues and organs, a phenomenon known as ectopic fat storage. The purpose of this review is to explore the possible locations of ectopic fat in key target-organs of cardiovascular control (heart, blood vessels and kidneys) and to propose how ectopic fat storage can play a role in the pathogenesis of cardiovascular diseases associated with obesity. In animals fed a high-fat diet, cardiac fat depots within and around the heart impair both systolic and diastolic functions, and may in the long-term promote heart failure. Accumulation of fat around blood vessels (perivascular fat) may affect vascular function in a paracrine manner, as perivascular fat cells secrete vascular relaxing factors, proatherogenic cytokines and smooth muscle cell growth factors. Furthermore, high amounts of perivascular fat could mechanically contribute to the increased vascular stiffness seen in obesity. Finally, accumulation of fat in the renal sinus may limit the outflow of blood and lymph from the kidney, which would alter intrarenal physical forces and promote sodium reabsorption and arterial hypertension. Taken together, ectopic fat storage in key target-organs of cardiovascular control may impair their functions, contributing to the increased prevalence of cardiovascular diseases in obese subjects.

Pathways from obesity to hypertension: from the perspective of a vicious triangle.

Obesity and arterial hypertension are important public health problems. Both overweight and hypertension predispose to cardiovascular diseases, such as myocardial infarction, stroke and renal failure. Moreover, overweight clearly predisposes to hypertension, and thus to an increased prevalence of cardiovascular diseases. This in turn favors inactivity and further weight gain, leading to an exacerbation of cardiovascular disorders. Obesity, hypertension and cardiovascular diseases thus contribute to three corners of a vicious triangle. It is within this conceptual framework that this paper reviews the pathogenesis of obesity-related hypertension, which is highly complex. Many factors act together to promote vasoconstriction and sodium retention. Leptin, free fatty acids and insulin, whose levels are increased in obesity, may act synergistically to stimulate sympathetic activity and vasoconstriction. In addition, obesity-induced insulin resistance and endothelial dysfunction may operate as amplifiers of the vasoconstrictor response. Finally, increased renal tubular reabsorption of sodium may also occur, caused by an increased renal sympathetic nerve activity, the direct effect of insulin, hyperactivity of the renin-angiotensin system and possibly by an alteration of intrarenal physical forces. All together, these factors will lead to sustained hypertension. Because the prevalence of obesity was steadily increasing in the last decades, leading to an increased prevalence of hypertension and cardiovascular disorders, obesity and hypertension will most likely become the health challenges of the twenty-first century.

Loss of nocturnal dipping of blood pressure and heart rate in obesity-induced hypertension in rabbits.

We have investigated in rabbits whether overfeeding and weight gain, which lead to hypertension, are associated with changes in circadian rhythm of blood pressure (BP) and heart rate, and whether the sympathetic nervous system is involved in these changes. In adult male rabbits, mean arterial pressure (MAP) and heart rate (HR) were monitored by telemetry 22 h a day. Daily MAP and HR records were divided into four equal intervals and used to calculate day-night differences. After a 1-week control period, animals were switched to a high-fat (HFD) ad libitum diet for 8 weeks. HFD increased whole day MAP and HR, and rapidly abolished the normal diurnal rhythm of MAP and HR. Since HFD abolished the nocturnal dip in MAP, but had little effect on daytime values, the loss of dipping appears to account for most of the hypertension in this model of obesity. In a separate set of rabbits, alpha- and beta-adrenergic blockade (terazosin + propranolol) prevented HFD-induced hypertension and attenuated the increase in HR by more than half. Adrenergic blockade alone abolished the diurnal rhythm of MAP, chiefly by preventing daytime elevation of MAP. The addition of HFD ad libitum did not further modify daily MAP or its circadian pattern. The diurnal rhythm of HR was relatively unaffected by alpha + beta blockade alone, but was abolished after switching to HFD. In conclusion, rabbits fed an HFD ad libitum develop hypertension and tachycardia associated with a loss of the normal diurnal rhythm of MAP and HR. The hypertension appears to be sympathetically mediated.

Role of the sympathetic nervous system during the development of obesity-induced hypertension in rabbits.

We have previously reported that weight gain induced by high-fat diet (HFD) leads to an increase in mean arterial pressure (MAP, +14%) and heart rate (HR, +31%) in the adult rabbit. In the present study, we tested the hypothesis that an increased activity of the sympathetic nervous system may contribute to the development of obesity-induced hypertension. A combination of alpha- and beta-adrenergic blockers (terazosin + propranolol) was chronically administered to rabbits housed in metabolic cages for continuous monitoring of arterial pressure by telemetry, 24 h a day. After 2 weeks of adrenergic blockade under control diet, animals were switched to HFD for the next 6 weeks. HFD induced a progressive increase in body weight, but no increase in mean arterial pressure (+0.2+/-2.5%) and a slight increase in heart rate (+14+/-3%). Time-control animals fed normal diet showed no changes in MAP or HR with long-term alpha- and beta-adrenergic blockade. Our results indicate that the activation of the sympathetic nervous system may play an important role in the pathogenesis of obesity-induced hypertension.

Direct and indirect methods used to study arterial blood pressure.

A number of different approaches exist for assessing blood pressure in experimental animals. Here, we briefly consider the traditional indirect (rodent tail-cuff) and direct (saline-filled catheter) methods of blood pressure measurement before going on to describe our experience with blood pressure telemetry in rabbits, rats, and mice. Blood pressure telemetry offers the ability to obtain a high-fidelity recording of blood pressure continuously, for relatively long periods of time, in conscious, freely moving animals, without the limitations of restraint or anaesthesia. Since some drift in telemeter offset and sensitivity are inevitable, recalibration of the telemeter devices immediately before implantation and following explantation is essential to ensure and document the accuracy of the blood pressure measurements. For long-term implantations, verification of the calibration can be performed in vivo, at least in the case of large animals, such as rabbits. Telemetry devices suitable for small animals, such as mice, are also available now, which will facilitate the accurate characterization of blood pressure in transgenic animals. Telemeter implantation methods in mice are presently difficult, with relatively low success rates being reported. However, validation of new methods, such as the insertion of the catheter tip via the carotid artery, may make the technique more widely accessible in the near future.

Serial changes in cardiovascular and renal function of rabbits ingesting a high-fat, high-calorie diet.

To explore the mechanisms of obesity-induced hypertension we analyzed the sequential changes in cardiovascular and renal function in adult rabbits switched to high-fat diet (HFD) for 8 weeks. Animals were housed in metabolic cages for continuous 24-h recording of arterial pressure by telemetry and daily urine collection. High-fat diet induced a progressive increase in body weight (+47%) and a rapid rise in mean arterial pressure, heart rate, and glomerular filtration rate that stabilized, respectively, at 14%, 31% and 68% greater than control values. Time-course analysis of changes in blood pressure may reveal two components of obesity-induced hypertension, an early phase related to HFD itself and a later phase related to weight gain.

The problem of pediatric malignancies in the developing world.

In industralized countries, 70 to 80% of children with cancer can be cured by expensive interdisciplinary teamwork and by cooperation on the national or international level. As a result of poor socio-economic conditions, worldwide, less than 20% of the approximately 185,000 children developing cancer each year get adequate treatment. This is also true for 14 to 15 million children dying each year of diarrhea and infections, but while this number is decreasing, the number of children with cancer is increasing. In "middle income" developing countries, cancer is now a leading cause of death for children between 5 and 15 years of age. The "geography" of pediatric cancer reveals complex interactions between environment, lifestyle, and carcinogenesis. The "mapping" of pediatric cancer is far from complete, and the investigation of carcinogenetic interactions has barely started. A great challenge is the planning of pediatric oncology in developing countries. The goals are to improve the access to treatment and treatment results. Even if pediatric oncology has a low priority, the institution, in each country or large province, of at least one pediatric cancer unit may improve not only cancer treatment but medical care in general. By promoting education, organizing meetings, and setting minimum standards for training and care, international organizations can contribute to the development of pediatric oncology worldwide.

Acute lymphoblastic leukaemia in childhood: cell proliferation without rest.

The percentage of non-cycling blast cells in children with untreated acute lymphoblastic leukaemia (ALL) was investigated by staining smears for statin, a nuclear protein specifically present in non-growing resting cells. Results were compared with purified normal CD34-positive progenitors. A low fraction of ALL and CD34-positive cells expressed statin (2.9 +/- 3.8% and 2.8 +/- 3.1%, respectively), the growth fraction assessed by staining for the nucleolar antigen p120 was 94% in both ALL and CD34-positive cell samples. From this analysis it can be concluded that the compartment of non-replicating cells in ALL as well as in normal CD34-positive precursor cells collected from peripheral blood is very small and that most cells are cycling.

Effect of bisphosphonates on the increase in bone resorption induced by a low calcium diet.

This study investigates whether bisphosphonate-treated rats are still able to adapt to low calcium supply through an increase in bone resorption assessed by measuring the urinary excretion of [3H]-tetracycline from chronically prelabeled rats. First it was shown that in this model, parathyroid hormone was responsible for the increase in bone resorption on the low calcium diet. In the second part, animals were treated with the three bisphosphonates-clodronate, alendronate, and ibandronate-given in two doses. Animals receiving a dose that already strongly inhibits bone resorption were still able to respond to a low calcium diet by increasing bone resorption, showing the potency of the latter as a stimulator of bone resorption. Higher doses were, however, able to blunt this response. As soon as the treatment was discontinued, this increase in bone resorption resumed with clodronate but not with alendronate or ibandronate.

[Pathogenesis of infection due to human immunodeficiency virus]. / Patogeneza infekcije virusom humane imunodeficijencije.

The constant increase in number vf patients with AIDS contributed to an increased interest for the mechanisms by which the human immunodeficiency virus provoked disorders of the immune system and disturbed functions of infected tissues and organs. The complex structure, tropism for some cell populations, specific life cycle and multiple interactions with host defence-system make the human immunodeficiency virus one of the most challenging pathogenic agents in medicine. The article deals with data from literature on some known facts as well as with assumptions which partially elucidate the pathogenesis of infection with human immunodeficiency virus.