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A rapid expansion of new treatment options in recent decades and the increasing volume of scientific evidence published on a daily basis have been followed by the necessity of introduction of clinical guidelines and therapeutic algorithms. The development of these guidelines and algorithms has also been driven by increased cost-awareness and the increasing pressure to improve cost-efficiency. The Serbian Physicians Society published "Therapeutic Guidelines for the Treatment of Schizophrenia" in 2003 and "Therapeutic Guidelines for the Treatment of Bipolar Affective Disorder" in 2004. The School of Medicine, University of Belgrade published "Therapeutic Guidelines for the Treatment of Depression" in 2004. All of these national guidelines, at the moment of development, were based upon up-to-date scientific evidence. According to the recently conducted survey at the Institute of Psychiatry, Clinical Centre of Serbia, about 65% of psychiatrists stated that they adhere to the national or relevant international therapeutic guidelines. When asked to cite which international or foreign guidelines in particular they used, approximately 50% failed to do so, while the other half cited mostly the APA Guidelines or NICE Guidelines. Among the national guidelines, physicians are, according to the survey, familiar with the Therapeutic Guidelines for the treatment of Schizophrenia (46.3%), Therapeutic Guidelines of Depression (41.5%) and Therapeutic Guidelines for the Treatment of Bipolar Affective Disorder (34.1%). The majority of Serbian psychiatrists rely on the efficacy and safety of the drugs as the major determining factors in the choice of therapy, bearing in mind the patients' best interests. However, it is unclear why such a discrepancy between practice and guidelines still persists, since guidelines also recommend therapy based on their safety and efficacy data. It is possible that a substantial percentage of psychiatrists obtain indicators on drugs' efficacy and safety from their personal professional experience. It is doubtful whether this knowledge is valid, or just represents unproven prescribers' habits. Furthermore, the influence on other factors, such as treatment costs or drug availability should be further investigated.

Background: Mood stabilizer augmentation of standard antidepressant drugs has been shown to be effective in treatment-resistant depression. Despite the reported high overall efficacy, lithium has been relatively underused in recent years. Lamotrigine, a novel anticonvulsant recently recognized as a mood stabilizer, seems to have putative antidepressive properties. The aim of the study was to investigate lamotrigine efficacy and tolerability as antidepressant augmentation for unipolar treatment-resistant depression compared to lithium., Subjects and Methods: 88 patients suffering from treatment-resistant Major depressive disorder, having acute recurrent depressive episodes according to DSM-IV criteria, were enrolled in the study. This was an open-label trial with a flexible dosing regimen. All patients, received antidepressants in full therapeutic doses. They were divided into two augmentation groups: 46 patients received 50-200 mg/day lamotrigine, and 42 patients received 600-1200 mg/day lithium. The Hamilton Rating Scale for Depression (HAM-D) and The Clinical Global Impression scale (CGI) were used to monitor therapeutic efficacy. Patients were evaluated weekly for an 8 week treatment period., Results: The HAM-D total score was significantly reduced in both treatment groups at the study endpoint, without any difference between the groups. However, significant clinical improvement was reached within the second treatment week in the lamotrigine group compared to the lithium group (p=0.01 vs. lithium). Lamotrigine showed significant efficacy on the HAM-D item 1(depressed mood; p=0.01), item 7 (work and interest; p=0.01) and CGI-Improvement scale (p=0.02). The drop-out rate due to treatment failure was lower in the lamotrigine group (n=1) compared to the lithium (n=4) group. Also, the incidence of side effects did not differ between the groups., Conclusions: Our results suggest that lamotrigine could be useful as augmentation of antidepressants for treatment-resistant unipolar depression. Also, lamotrigine may accelerate the onset of antidepressant action, and therefore might be useful in treatment of major depression in general.

As one of the most potent and substantial form of mass communication, film exercises a very significant influence upon the perceptions of the audience, especially in relation to mental illness issues, and that perception is very much blurred with populists' misinterpretation and lack of awareness regarding problems faced by persons suffering from mental disorders. Movies such as "Psycho", "One Flew Over Cuckoo's Nest", "Exorcist", despite being valuable in an artistic sense, corroborated and encouraged confusion and undermined the clarity and certainty concerning the fine line separating mental health from mental illness. Modern film makers and movie theoreticians try to overcome these limitations which are often generated by exploitation of stereotypes and myths referring to mentally ill people. This paper defines and discusses the most frequent thematic stereotypes seen in movies which are perpetuating stigmatization of mentally ill people. They are: free-spirited rebel, maniac on a killing spree, seducer, enlightened member of society, narcissistic parasite, beastly person (stereotype of animal sort). Psychiatry and cinematography are linked inseparably not only because they creatively complement each other, but also as an opportunity of mutual influences blending into didactical categories and professional driving forces, benefiting both the filmmakers' and the psychiatrists' professions.

A case is reported of a 36-year-old male, found dead in his locked room, lying on a bed, dressed in his mother's clothes, with a plastic bag over his head, hands tied and with a barrel wooden cork in his rectum. Two pornographic magazines were found on a chair near the bed, so that the deceased could see them well. Asphyxia was controlled with a complex apparatus which consisted of two elastic luggage rack straps, the first surrounding his waist, perineum, and buttocks, and the second the back of his body, and neck. According to the psychological autopsy based on a structured interview (SCID-I, SCID-II) with his father, the deceased was single, unemployed and with a part college education. He had grown up in a poor family with a reserved father and dominant mother, and was indicative of fulfilling DSM-IV diagnostic criteria for alcohol dependence, paraphilia involving hypoxyphilia with transvestic fetishism and anal masturbation and a borderline personality disorder. There was no evidence of previous psychiatric treatment. The Circumstances subscale of Beck's Suicidal Intent Scale (SIS-CS) pointed at the lack of final acts (thoughts or plans) in anticipation of death, and absence of a suicide note or overt communication of suicidal intent before death. Integration of the crime scene data with those of the forensic medicine and psychological autopsy enabled identification of the event as an accidental death, caused by neck strangulation, suffocation by a plastic bag, and vagal stimulation due to a foreign body in the rectum.

The authors present the development of the concept of mental disease and treatment in Serbian medicine. Serbian medieval medicine did not acknowledge fortune telling, sorcery, the use of amulets and magical rituals and formulas. These progressive concepts were confirmed by the Church and the Serbian state in what is known as Dusan's Code. The Historical data on the establishment of the first psychiatric hospital in the Balkans "Home for the Unsound of Mind" at Guberevac, Belgrade, in 1861 and its founders is reviewed. After World War I, in 1923, the Faculty of Medicine was established in Belgrade to which the coryphaei of Serbian medicine educated in Europe, mostly in France and Germany, flocked and that same year the Psychiatry Clinic of the Faculty of Medicine in Belgrade was set up. Its first seat was on the premises of the Mental Hospital in Belgrade, and it became a training base and laid the foundations of the future Neuropsychiatry Clinic in Belgrade, which in time evolved into the nursery of psychiatric professionals for all of Serbia. The most important data on the further development of psychiatry up to date are presented.

Introduction: This paper deals with medicolegal aspects of the hospital treatment of patients suffering from severe mental disorders and who are prone to violent behaviour, dangerous to self and others. Violent acts in this study were defined as deliberate and nonconsensual acts of actual, attempted or threatened harm to a person or persons, and classified into categories of any type of violence, physical violence and non-physical violence, which is in accordance with approaches used in other risk assessment researches,, Outline of Cases: The authors present four cases of mentally ill inpatients whose violent behaviour toward self or other persons resulted in self-destruction and physical aggression against other persons. The presented cases involved: 1) self-injury in a patient with acute organic mental disorder after jumping through a hospital window, 2) suicide by drowning of a patient with acute mental disorder after escaping from intensive care unit, 3) suicide in a depressive patient after escaping from a low-security psychiatry unit, 4) physical violence against body and life of other persons in a patient with chronic mental disorder., Conclusion: The presented cases are considered to be rare in clinical practice and risk of violent behaviour and the consequent danger of mentally ill inpatients may be efficiently predicted and prevented with appropriate hospital management based on 1) repeated escalation of violent behaviour and 2) protection of the patient and others. Hence, if the physician in order to prevent harmful consequences, does not apply all the necessary measures, including appropriate diagnostic and therapeutic procedures, as well as treatment in an adequate setting, such act is against the Criminal Law of the Republic of Serbia which sanctions physician's negligence. Also, according to the Law on Obligations of the Republic of Serbia this presents a legal ground for damage claim and the requirement of liability for nonmaterial damage within a civil procedure.

Objectives: The aim of this study was to establish the morbidity structure among testators whose wills were challenged as well as to reveal if there is a specific relationship between certain diagnostic categories in the testators' health status and forensic psychiatry expert opinion on testamentary incapacity., Subjects and Methods: The authors analyzed 156 consecutive forensic psychiatry reports on retrospective, determination of testamentary capacity made in the Forensic Psychiatry Centre, Institute of Psychiatry, Belgrade in the period 1965 - 2005. The wills covered by this study were mostly made by male, 65 years old or older testators, with primary education, who executed a holograph will and survived it for less than a year., Results: Testamentary incapacity for medical reasons was established in 47% of the testators, while a strong, statistically significant relationship between a diagnostic category and testamentary incapacity was established among the testators suffering from an organic mental disorder (Chi-square=133.256, p=0.000) or a substance induced mental disorder (Chi-square=6.971, p=0.008)., Conclusion: Testamentary capacity is a specific focus of medical assessment given that the evidence for overturning a will is generally dependent upon medical assessment. In that respect, much litigation and expenses could be avoided if medical experts were given a chance to correctly assess the testamentary capacity of a person at the time of making a will. The fact remains that our findings may not be a representative cross-section of the general population, and this important issue certainly deserves to be addressed by future research based on a larger sample.

Introduction: Stuttering is a functional impairment of speech, which is manifested by conscious, but nonintentionally interrupted, disharmonic and disrhythmic fluctuation of sound varying in frequency and intensity. Aetiology of this disorder has been conceived within the frame of theoretical models, which tend to connect genetic and epigenetic factors., Objective: The goal of the paper was to study the characteristics of the family functioning of stuttering children in comparison to the family functioning of children without speech disorder, which confirmed the justification of the introduction of family orientated therapeutic interventions into the therapy spectrum of child stuttering., Method: Seventy-nine nucleus families of 3 to 6-year-old children were examined; of these, 39 families had stuttering children and 40 had children without speech disorder. The assessment of family characteristics was made using the Family Health Scale, an observer-rating scale which according to semistructured interview and operational criteria, measures 6 basic dimensions of family functioning: Emotional State, Communication, Borders, Alliances, Adaptability & Stability, Family Skills. A total score calculated from the basic dimensions, is considered as a global index of family health., Results: Families with stuttering children compared to families with children without speech disorder showed significantly lower scores in all the basic dimension of family functioning, as well as in the total score on the Family Health Scale., Conclusion: Our research results have shown that stuttering children in comparison with children without speech disorder live in families with unfavourable emotional atmosphere, impaired communication and worse control over situational and developmental difficulties, which affect children's development and well-being. In the light of previous research, the application of family therapy modified according to the child's needs is now considered indispensable in the therapeutic approach to stuttering children. The assessment of family characteristics with special reference to the ability of parents to recognize specific needs of children with speech disorder and adequate interaction, as well as readiness of parents for therapeutic collaboration are the necessary elements in legal custody evaluations.

Objectives: Psychometric properties of the DSM-IV Axis V scales in measuring adaptational functioning of psychotraumatised veterans have been chosen as the focus of this study., Subjects and Methods: The reliability and validity of the Global Assessment of Functioning Scale (GAF), the Social and Occupational Assessment Scale (SOFAS), and the Global Assessment of Relational Functioning (GARF) were examined in a clinical sample of 129 veterans with posttraumatic stress disorder (PTSD)., Results: The interrater reliability of the GAF (ICC=0.82) and the SOFAS (ICC=0.83) was excellent, while the interrater reliability of the GARF (ICC=0.75) was good. Correlations with other clinician-rated scales of psychopathology and overall functioning showed that the GAF is primarily related to a reduction in functioning due to psychiatric symptoms, while an assessment of functioning beyond psychopathology, considering the effects of the individual's general medical condition as well, was provided by the SOFAS and the GARF, which is of importance for a comprehensive evaluation of the patients' health status. The factor analysis of the Axis V scales revealed a theoretically meaningful, single common factor (variance accounted for by the extracted factor = 76.91%), while observed differences, between the subjects with complete and partial PTSD, in scores on the axis V scales support further use of the axis V scales as useful outcome variables., Conclusion: The issue of a valid and reliable measurement of functional impairment is of paramount importance not only in the domain of clinical psychiatry but in forensic practice as well. In this respect, our findings give strong support to extending the scope of the DSM axis V scales with the two experimental scales which provide both conceptual framework and useful tools for reliable and valid evaluation of adaptatinal functioning in persons suffering from PTSD.

Background/aim: . Metabolic syndrome and malnutrition represent metabolic abnormalities which significantly characterize patients on haemodialysis. The aim of the study was to determine the incidence and find characteristics of metabolic disbalance in patients on haemodialysis., Methods: The study involved 124 patients on chronic haemodialysis at the Clinical Centre Kragujevac. There were analyzed demographic and anthropometric characteristics of the examined patients. Of clinical characteristics, there were determined smoking habit, time on dialysis, arterial pressure; of comorbid states there were recorded heart diseases and diabetes mellitus. Routine biochemical analyses were carried out by a standard laboratory procedure., Results: Metabolic syndrome was found in 29.8% of the examined patients. The patients with metabolic syndrome were older as compared to the patients without metabolic syndrome (58.45 +/- 12.91 vs 52.25 +/- 11.63 years). The values of systolic pressure (143.88 +/- 19.75 vs 133.01 +/- 22.93 mmHg; p = 0.014), body mass index (21.2 +/- 3.71 vs 19.4 +/- 2.88 kg/m2;p = 0.001), fat body mass (19.57 +/- 8.47 vs 16.45 +/- 5.82%; p = 0.0002) and waist scope (89 +/- 12.54 vs 96 +/- 12.34 cm; p = 0.0001) were significantly higher in the patients with metabolic syndrome as compared to those without metabolic syndrome. The values of erythrocytes (3.4 +/- 0.45 vs 19 +/- 0.53 x 10(12); p = 0.04) and hemoglobin (107 +/- 15.76 vs 101 +/- 13.87 g/l; p = 0.009), glycaemia (9.5 +/- 8.15 vs 5.6 +/- 1.4 mmol/l; p = 0.04) triglycerides (2.44 +/- 1.8 vs 1.41 +/- 0.64 mmol/l; p = 0.007), HDL cholesterol (1.11 +/- 0.19 vs 0.82 +/- 0.25 mmol/l; p = 0.005) and albumins (32.5 +/- 5.6 vs 29.5 +/- 3.7 g/l; p = 0.007) were statistically higher in the patients with metabolic syndrome than in patients without disturbance. Diabetes mellitus was a significant etiological factor of renal insufficiency in the patients with metabolic syndrome (p = 0.008)., Conclusion: In our study approximately 30% of patients on haemodialysis had pronounced metabolic syndrome. The older, more obese men with increased levels of triglycerides and glucose in the serum dominated among them. Diabetes mellitus was a leading etiological factor of renal insufficiency in these patients.

Introduction/aim: Gastric acid is a key factor in the pathophysiology of gastroesophageal reflux disease. A plausible mechanism by which the Helicobacter pylori infection might protect against reflux disease is by its propensity to produce atrophic gastritis. The aim of the study was to establish the influence of Helicobacter pylori infection on the occurrence of gastroesophageal reflux in patients with different stages of renal insufficiency., Methods: The examination was organized as a prospective, clinical study and involved 68 patients--33 patients with preterminal stage of renal failure and 35 patients with terminal renal insufficiency. Due to dyspeptic difficulties, in all the patients there was preformed upper esophagogastroscopy and Helicobacter pylori infection was found by ureasa test., Results: The patients with preterminal renal insufficiency were significantly younger than patients with terminal renal failure (53.4 +/- 11.1 vs. 65.4 +/- 12.3 years; p = 0.014). There was found a statistically significant difference between the groups in Helicobacter pylori infection (p = 0.03), hiatal hernia (p = 0.008), gastroesophageal reflux disease (p = 0.007), and duodenal ulcer (p = 0.002). Using the multiple non-parametric correlative analysis there was confirmed a negative correlation between Helicobacter pylori infection and gastro-esophageal reflux disease (Kendal tauB = -0.523; p = 0.003) and hiatal hernia (Kendal tauB = 0.403; p = 0.021), while there was found a positive correlation between gastro-esophageal reflux disease and hiatal hernia (Kendal tauB = 0.350; p = 0.044)., Conclusion: Helicobacter pylori infection is a significant protective parameter of the incidence of gastro-esophageal reflux disease in patients with both pre-terminal and terminal renal insufficiency.

Arterial hypertension (AH) is the most important independent risk factor of cardiovascular diseases. The prevalence of AH is higher than it was several decades before, and in Europe it is approximately 40%. A higher prevalence of AH has been reported in Europe than in the United States and Canada. According to the results of epidemiology of arterial hypertension in Croatia study (EH-UH), the prevalence of AH in Croatia is 37.5%. Women are more aware, they were treated more often, and blood pressure control was more frequently achieved than in men. However, body mass index and socioeconomic factors have a greater influence on blood pressure values and prevalence of AH in women. A low level of health education and inappropriate treatment are the most important reasons for the poor blood pressure control observed. Measures of primary prevention should be performed continuously and adjusted to special population subgroups. As an increase of obesity and hypertension was observed in school children, these measures should start at that age.

Aim: An anonymous survey was performed in a sample of 454 adult patients from the catchment population of eight family medicine teams at Dugave-Travno Clinic in Zagreb to assess their attitudes towards the family physician concept, its advantages and shortcomings. These family medicine teams providing care for 16,077 insures also the number of families with all their members receiving care from these teams., Method: The method of descriptive statistics was used., Results: Data were obtained on the number of families where only some members received care at the same physician's office and on the proportion of individual family members receiving care at family medicine offices. The sample indicated that more than half of patients received care from the same family physician, and that only one tenth of patients were without their family medical file. Study subjects considered that the family doctor institution contributed to improved care and were aware of the advantages of the family doctor concept. The concept of comprehensive family treatment could currently be implemented in half of the patients. However, the other half are broken up, receiving medical care at offices of different teams., Conclusion: The family physician concept could be implemented in two ways: exchange of the insures among the teams at a particular clinic providing care for defined populations, and in administrative way. The family physician concept would require two strategic decisions: establishment and development of group practice, and virtual linkage of the family member medical data through an integrated primary health care information system.

The final goal of palliative care is symptom relief and improving the quality of life. Around 70% of cencer patients suffer pain. Therapy and care provided for dying cancer patients by general practitioners at Dugave-Travno GP Office were investigated. Medical records of 70 cancer patients were collected and analyzed. Sixty-seven patients had died. A total of 76 cancers at 22 various sites were diagnosed. There were 79 associated diseases diagnosed in 44 patients, along 43 diseases related to malignant disease in 26 patients. Physicians provided home nursing for 30 patients. In 66 cases family provided support. Physicians collaborated with community health nurses in 38 cases. A total of 66 patients were using analgesic therapy, 37 patients continuously, and 48 patients for up to one year. In 56 patients analgesic drugs were administered orally, in 25 parenterally, in 16 rectally, and in 21 patients transdermally. Physicians prescribed opioid therapy in 55 patients: codeine in 2, tramadol in 46, pentazocine in 7, methadone in 5, Kapanol in 15 and fentanyl in 21 patients. Sixty patients received adjuvant drug therapy. A total of 59 patients were hospitalized in terminal stage of the disease. Study results showed a high rate of associated diseases and diseases related to malignant disease in cancer patients. The collaboration between general practitioners and family members was satisfactory. Community health services should be improved, and the World Health Organization guidelines on palliative care, management of malignant pain in particular, should be more thoroughly followed.

Pruritus is one of the commonest symptoms of dermatologic appearances in uraemic syndrome and it occurs in 90% of patients on dialysis with different etiology and pathophysiology. The aim of the study was to estimate the frequency of uraemic pruritus and the comparison with clinical and biochemical parameters in 124 patients treated by chronic haemodialysis at Department of Haemodialysis, Clinical Centre in Kragujevac. The routine laboratory analyses were carried out in the examined patients and the concentration of parathyroid hormone was determined. The study was based on data from history of disease and questionnaire taken out in all patients. Of 124 patients 46.8% had symptoms of uraemic pruritus. Concentration of urea, albumin concentration, iron, parameters UIBC, as well as hyperglycemia and time on dialysis are the significant are significantly correlated with uraemic pruritus. 27.6% of the examined patients had itching of all the body. Between the patients with localized itching and patients with generalized itching, there are statistically significant differences in the following parameters: erythrocyte count, hemoglobin concentration, hematocrit and TIBC, as well as glycemia concentration.

Background/aim: Numerous clinical studies have shown that the incidence of artheriosclerosis is higher in patients with progressive renal insufficiency. The aim of this study was to examine the incidence of artheriosclerosis in patients on chronic hemodialysis and its influence on survival and functioning of vascular access., Methods: The study was organized as one-year prospective study. All the patients had arteriovenous fistulas native as a vascular access. The study analyzed demographic, biochemical, clinical and Doppler echomorphological characteristics of the patients in order to make an evidence of artheriosclerotic incidences as compared to functioning arteriovenous fistulas for hemodialysis., Results: The examined patients were of the mean age 55.7+/-12.68 years. Of them, 53.8% were males and 46.2% females. Functioning arteriovenous fistulas for haemodialysis were found in 56.8% of the examined patients. Concentration of hemoglobin was a significant parameter of functioning fistula (group with complications--89<--14.034 vs. group with no complications-- 96.6+/-17.71;p = 0.0489. An amount of urea removed (URR) was a statistically more significant parameter among the patients without fistula complications: (group with complications--58.67+/-7.92% vs. group with no complications--62.80+/-7.53%; p = 0.037). A Cox regressive analysis of an index of Doppler parameters of the carotid arteries found no statistical significance between the examined groups. There was a positive correlation between artheriosclerosis and the age, as well as the time on dialysis. In multiple regression, where intima media is a dependent and the age and time on dialysis independent variables, the regressive model was statistically significant (F = 8.22, p = 0.001). Both independent variables had statistically significant inclinations, p < 0.01., Conclusion: Anemia and the level of urea elimination, as a statistically significant indicator of hemodialysis adequacy, were in correlation with the risk for fistula complications. B-mode ultrasonography of the carotid arteries is a significant non-invasive method for detecting artheriosclerosis. Intima-media thickness of the carotid arteries was an important marker of artheriosclerosis correlating significantly with the age and time on dialysis, but not with the traditional risk factors.

Brief periods of ischemia and reperfusion that precede sustained ischemia lead to a reduction in myocardial infarct size. This phenomenon, known as ischemic preconditioning, is mediated by signaling pathway(s) that is complex and yet to be fully defined. AMP-activated kinase (AMPK) is activated in cells under conditions associated with ATP depletion and increased AMP/ATP ratio. In the present study, we have taken advantage of a cardiac phenotype overexpressing a dominant negative form of the alpha2 subunit of AMPK to analyze the role, if any, that AMPK plays in preconditioning the heart. We have found that myocardial preconditioning activates AMPK in wild type, but not transgenic mice. Cardiac cells from transgenic mice could not be preconditioned, as opposed to cells from the wild type. The cytoprotective effect of AMPK was not related to the effect that preconditioning has on mitochondrial membrane potential as revealed by JC-1, a mitochondrial membrane potential-sensitive dye, and laser confocal microscopy. In contrast, experiments with di-8-ANEPPS, a sarcolemmal-potential sensitive dye, has demonstrated that intact AMPK activity is required for preconditioning-induced shortening of the action membrane potential. The preconditioning-induced activation of sarcolemmal K(ATP) channels was observed in wild type, but not in transgenic mice. HMR 1098, a selective inhibitor of sarcolemmal K(ATP) channels opening, inhibited preconditioning-induced shortening of action membrane potential as well as cardioprotection afforded by AMPK. Immunoprecipitation followed by Western blotting has shown that AMPK is essential for preconditioning-induced recruitment of sarcolemmal K(ATP) channels. Based on the obtained results, we conclude that AMPK mediates preconditioning in cardiac cells by regulating the activity and recruitment of sarcolemmal K(ATP) channels without being a part of signaling pathway that regulates mitochondrial membrane potential.

Poor control of blood pressure (BP) is one of the main reasons for high cardiovascular mortality and morbidity. The aim of this study was to analyse control of BP in outpatient settings in four biggest towns in Croatia. The study included 412 medical doctors (GP) and 7031 middle-aged patients (62.9 +/- 11.5 years). Mean BP in treated patients was 162.9 +/- 16.8/95.6 +/- 9.9 mmHg. There were no statistically significant differences in systolic (p = 0.173) and diastolic (p = 0.561) BP between men and women. In this group of patients only 8% achieved target BP values. In contrast, and surprisingly, 44.5% of medical doctors and 72% of patients were satisfied with obtained BP control. Higher percentage of male patients vs. female were satisfied with blood pressure control (81.9%:66.9%). BMI < 25 was registered in 22.9% of hypertensive patients, and there was statistically significant difference in BMI between men and women (chi2 = 56.769, p < 0.001). In this study we found a statistically significant difference of hypertension in regard to BMI in both sexes (chi2 = 46.339, p < 0.001; chi(z)2 = 45.992, p = 0.024). BMI was in correlation with severity of hypertension as well as with obtained treatment result. BMI was in correlation with the number of prescribed drugs. According to this, patients with BMI < 25 were prescribed less drugs than those with BMI > 30 (1.4:1,6 p = 0.001). BP control in Croatia is, according to this study, very poor. The main reason for such situation is, beside obesity which determines the stage of hypertension and BP control in both sexes, insufficiently developed conscience in patients and doctors about the importance of stronger blood pressure control. The results indicate the necessity for the more intensive education of the population.

Obesity significantly increases the risk for the occurrence of cardiovascular disease in patients with essential hypertension. The aim of the study was to assess the frequency of obesity, measured by different methods, in patients with essential hypertension, its effect on arterial pressure, and to determine the best correlation between indicators of obesity and arterial pressure. The study included 88 patients with essential hypertension, 32 males, mean age 59.4 (+/- 10.4) years, and 56 females, mean age 62.9 (+/- 8.8) years. Body weight (BW) and height (BH), waist circumference (WC), and body mass index (BMI) were measured for each subject. Arterial pressure was determined using mercury sphygmomanometer. Overweight patients were defined as those with BMI 25-29.9 kg/m2, while obese as those with > or = 30 kg/m2. Abdominal obesity was assessed by WC. WC values exceeding 102 cm for men and 88 cm for women indicated obesity. Body measures of male patients were higher than those for women (BW 92.5 (+/- 14.5) vs 76.7 (+/- 11.5) p < 0.001; BH 175.4 (+/- 7.4) vs 163.4 (+/- 5.8) p < 0.001), significantly higher waist circumference values (102.4 (+/- 12.2) vs 94.1 (+/- 13.9) p = 0.006), with no differences in age, BMI, and arterial pressure values (p > 0.05). Also, no differences were observed in the number of uncontrolled hypertensive patients or number of overweight or obese patients (p > 0.05). The number of obese patients did not differ significantly with regard to the various measurement methods employed (BMI: M 50%, F 37%; waist measurement: M 51%, F 54%). A significant difference was noted in arterial pressure values only in the male patient group on comparing patients with normal BW and obese patients (systolic blood pressure (SBP) 156 (+/- 22.5) vs 142 (+/- 6.4) p = 0.04; diastolic blood pressure (DBP) 94 (+/- 11.6) vs 82.5 (+/- 6.4) p = 0.05). The correlation between obesity indicators and arterial pressure was significant for WC only in the male group (SBP r = 0.33, DBP r = 0.35, p < 0.05). The frequency of obesity does not differ with regard to the determined obesity indicators. Obese men have higher risk for increased arterial pressure values. WC values correlate better with arterial pressure values as it is a more accurate indicator of abdominal obesity.

ATP-sensitive K+ (K(ATP)) channels are present in the sarcolemma of cardiac myocytes where they link membrane excitability with the cellular bioenergetic state. These channels are in vivo composed of Kir6.2, a pore-forming subunit, SUR2A, a regulatory subunit, and at least four accessory proteins. In the present study, real-time RT-PCR has demonstrated that of all six sarcolemmal K(ATP) channel-forming proteins, SUR2A was probably the least expressed protein. We have generated mice where the SUR2A was under the control of a cytomegalovirus promoter, a promoter that is more efficient than the native promoter. These mice had an increase in SUR2A mRNA/protein levels in the heart whereas levels of mRNAs of other channel-forming proteins were not affected at all. Imunoprecipitation/Western blot and patch clamp electrophysiology has shown an increase in K(ATP) channel numbers in the sarcolemma of transgenic mice. Cardiomyocytes from transgenic mice responded to hypoxia with shortening of action membrane potential and were significantly more resistant to this insult than cardiomyocytes from the wild-type. The size of myocardial infarction in response to ischemia-reperfusion was much smaller in hearts from transgenic mice compared to those in wild-type. We conclude that overexpression of SUR2A generates cardiac phenotype resistant to hypoxia/ischemia/reperfusion injury due at least in part to increase in levels of sarcolemmal K(ATP) channels.

Recent studies indicate that the LKB1 is a key regulator of the AMP-activated protein kinase (AMPK), which plays a crucial role in protecting cardiac muscle from damage during ischemia. We have employed mice that lack LKB1 in cardiac and skeletal muscle and studied how this affected the activity of cardiac AMPKalpha1/alpha2 under normoxic, ischemic, and anoxic conditions. In the heart lacking cardiac muscle LKB1, the basal activity of AMPKalpha2 was vastly reduced and not increased by ischemia or anoxia. Phosphorylation of AMPKalpha2 at the site of LKB1 phosphorylation (Thr172) or phosphorylation of acetyl-CoA carboxylase-2, a downstream substrate of AMPK, was ablated in ischemic heart lacking cardiac LKB1. Ischemia was found to increase the ADP-to-ATP (ADP/ATP) and AMP-to-ATP ratios (AMP/ATP) to a greater extent in LKB1-deficient cardiac muscle than in LKB1-expressing muscle. In contrast to AMPKalpha2, significant basal activity of AMPKalpha1 was observed in the lysates from the hearts lacking cardiac muscle LKB1, as well as in cardiomyocytes that had been isolated from these hearts. In the heart lacking cardiac LKB1, ischemia or anoxia induced a marked activation and phosphorylation of AMPKalpha1, to a level that was only moderately lower than observed in LKB1-expressing heart. Echocardiographic and morphological analysis of the cardiac LKB1-deficient hearts indicated that these hearts were not overtly dysfunctional, despite possessing a reduced weight and enlarged atria. These findings indicate that LKB1 plays a crucial role in regulating AMPKalpha2 activation and acetyl-CoA carboxylase-2 phosphorylation and also regulating cellular energy levels in response to ischemia. They also provide genetic evidence that an alternative upstream kinase can activate AMPKalpha1 in cardiac muscle.

Cardiac sarcolemmal ATP-sensitive K+ (K(ATP)) channels, composed of Kir6.2 and SUR2A subunits, are regulated by intracellular ATP and they couple the metabolic status of the cell with the membrane excitability. On the basis of previous studies, we have suggested that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) may be a part of the sarcolemmal K(ATP)-channel protein complex. A polypeptide of approximately 42 kDa was immunoprecipitated with an anti-SUR2A antibody from guinea-pig cardiac membrane fraction and identified as GAPDH. Immunoprecipitation/western blotting analysis with anti-Kir6.2, anti-SUR2A and anti-GAPDH antibodies showed that GAPDH is a part of the sarcolemmal K(ATP)-channel protein complex in vivo. Further studies with immunoprecipitation/western blotting and the membrane yeast two-hybrid system showed that GAPDH associates physically with the Kir6.2 but not the SUR2A subunit. Patch-clamp electrophysiology showed that GAPDH regulates K(ATP)-channel activity irrespective of high intracellular ATP, by producing 1,3-bisphosphoglycerate, a K(ATP)-channel opener. These results suggest that GAPDH is an integral part of the sarcolemmal K(ATP)-channel protein complex, where it couples glycolysis with the K(ATP)-channel activity.

This review deals with bibliography on Munchausen syndrome by proxy (MSbP). The name of this disorder was introduced by English psychiatrist Roy Meadow who pointed to diagnostic difficulties as well as to serious medical and legal connotations of MSbP. MSbP was classified in DSM-IV among criteria sets provided for further study as "factitious disorder by proxy", while in ICD-10, though not explicitly cited, MSbP might be classified as "factitious disorders" F68.1. MSbP is a special form of abuse where the perpetrator induces somatic or mental symptoms of illness in the victim under his/her care and then persistently presents the victims for medical examinations and care. The victim is usually a preschool child and the perpetrator is the child's mother. Motivation for such pathological behavior of perpetrator is considered to be unconscious need to assume sick role by proxy while external incentives such as economic gain are absent. Conceptualization of MSbP development is still in the domain of psychodynamic speculation, its course is chronic and the prognosis is poor considering lack of consistent, efficient and specific treatment. The authors also present the case report of thirty-three year-old mother who had been abusing her nine year-old son both emotionally and physically over the last several years forcing him to, together with her, report to the police, medical and educational institutions that he had been the victim of rape, poisoning and beating by various individuals, especially teaching and medical staff. Mother manifested psychosis and her child presented with impaired cognitive development, emotional problems and conduct disorder.

A consensus reached by the medical profession, Croatian Institute of Health Insurance, Croatian Institute of Public Health, and Ministry of Health constitutes a solution to the problem of a data standard required in building an information system for primary health care. This consists of accepting ICPC-2 as a data standard for our Family Medicine, Pediatrics and Women's Health. The classification structure of the International Classification of Primary Care allows, recommends and urges that special codes be established by individual states or local authorities when registering patients' reasons for seeking medical aid or medical procedures. Namely, it urges the authorities to set the codes for such reasons about which a state or local agreement or determination has been made. This is the first public presentation of the proposal Croatia's Additions to the International Classification of Primary Care. They are essential to its implementation in our health insurance, health statistics and medical informatics.

In this study, legal status of the mentally ill has been discussed in the context of Serbian legislation. The topics covered are the following: 1) the admission of persons with mental illness to psychiatric institution, 2) general (legal) competence, 3) marital relations of persons with mental illness, 4) legal definitions of sanity and security measures of medical character. Serbia still has no general law on mental health which would be in accordance with European standards, and the existing legislation which deals with the rights of persons with mental illness is, to a large extent, incomplete and obsolete. The author appeals for passing the law on mental health which should: a) follow modern trends in psychiatry concerning the protection of human rights with the basic goal to protect society and mentally ill persons, b) to protect the professional and moral integrity of psychiatrists, c) to provide ethically and professionally acceptable authorization for the use of force, if necessary, in order to prevent criminal acts and/or self-injuries in patients suffering from severe psychical disorders, d) to conceptualize forensic psychiatric treatment (the security measures, corrective psychiatry) and the programs of rehabilitation as an integral part of the community mental health protection system.

Effects of V(1) (OPC-21268) and V(2) (OPC-31260) vasopressin antagonists on blood pressure (BP) short-term variability were investigated in adult spontaneously hypertensive rats (SHR) under basal conditions and after the stimulation of vasopressin release by hemorrhage. BP was recorded intra-arterially and sampled at 20 Hz to be analyzed on a personal computer. BP time spectra were calculated on 30 stationary overlapping 2048 point-time series. Spectral power was estimated in total (0.00976 - 3 Hz), very low frequency (VLF: 0.00976 - 0.195 Hz), low frequency (LF: 0.195 - 0.605 Hz), and high frequency (HF: 0.8 - 3 Hz) regions. Under basal conditions a V(1) antagonist (5 mg/kg, i.v.) decreased BP without affecting BP variability, while combined (V(1) + V(2)) blockade or V(2) blockade (1 mg/kg, i.v.) alone did not affect cardiovascular parameters. Mild hemorrhage (5 ml/kg per min) increased HF-BP variability, while moderate (10 ml/kg per min) and massive (15 ml/kg per min) hemorrhage did not affect it. In V(1), but not V(2), antagonist pre-treated SHR HF-BP increased significantly after moderate and massive hemorrhage. V(1) or V(2) antagonist pre-treatment also enhanced VLF-BP variability during massive hemorrhage. Moreover V(1) blockade prevented hemorrhage-induced bradycardia, while V(2) blockade potentiated it. It follows that in adult SHR, vasopressin buffers BP oscillations in HF and VLF frequency domains only in hypovolaemic conditions and that the modulation of the autonomic adjustment of the HR to hemorrhage by vasopressin is preserved.

This review highlights some recent research addressing sarcolemmal K(ATP) channels in ageing. These channels are abundant in cardiac myocytes where they are essential in coupling the cellular metabolic state with membrane excitability. The opening of sarcolemmal ATP-sensitive K+ (K(ATP)) channels occurs during ischaemia and protect the heart against injury. Age-dependent changes in the myocardial susceptibility to ischemia have been observed in different species, including humans. Recent research has demonstrated that ageing is associated with decrease in numbers of sarcolemmal K(ATP) in hearts from females, but not males. This phenomenon seems to be associated with age-dependent decrease in concentration of circulating estrogens. In the heart, SUR2A, a regulatory subunit of K(ATP) channels, is present in excess over Kir6.2, a pore-forming K(ATP) channel subunit. The consequence of this is that SUR2A is a subunit that controls the number of sarcolemmal K(ATP) channels. Estrogens specifically up-regulate SUR2A and, thereby, control the number of sarcolemmal K(ATP) channels. Age-dependent loss of sarcolemmal K(ATP) channels creates a cardiac phenotype more sensitive to ischaemia, which may explain, at least in part, an ageing-associated decrease of myocardial tolerance to stress that occurs in elderly women., (Copyright 2003 Elsevier Ireland Ltd.)

We employed Cre/loxP technology to generate mPDK1(-/-) mice, which lack PDK1 in cardiac muscle. Insulin did not activate PKB and S6K, nor did it stimulate 6-phosphofructo-2-kinase and production of fructose 2,6-bisphosphate, in the hearts of mPDK1(-/-) mice, consistent with PDK1 mediating these processes. All mPDK1(-/-) mice died suddenly between 5 and 11 weeks of age. The mPDK1(-/-) animals had thinner ventricular walls, enlarged atria and right ventricles. Moreover, mPDK1(-/-) muscle mass was markedly reduced due to a reduction in cardiomyocyte volume rather than cardiomyocyte cell number, and markers of heart failure were elevated. These results suggested mPDK1(-/-) mice died of heart failure, a conclusion supported by echocardiographic analysis. By employing a single-cell assay we found that cardiomyocytes from mPDK1(-/-) mice are markedly more sensitive to hypoxia. These results establish that the PDK1 signalling network plays an important role in regulating cardiac viability and preventing heart failure. They also suggest that a deficiency of the PDK1 pathway might contribute to development of cardiac disease in humans.

The study comprised 150 epileptic patients treated at the Institute of Neurology of the Clinical Centre Novi Sad. The optimal therapy with least adverse effects and seizures was achieved in patients in whom measurement of serum concentration of antiepileptic drugs was performed. Patients were divided into five groups with respect to the therapy they received: I--carbamazepane; II--valproic acid; III--polytherapy with phenobarbitone and diphenylhydantoin; IV--phenobarbitone and valproic acid; and V--phenobarbitone, valproic acid and carbamazepine. No adverse effects were recorded in over 60% of patients on monotherapy, 35% of patients who received two anticonvulsants, and 30% of patients who received three anticonvulsants. Significant correlation between drug dosage and blood drug concentration (r > 0.5) was found in polytherapy with phenobarbitone, carbamazepine and valproic acid (r = 0.66); and phenobarbitone and diphenylhydantoin (r = 0.53).

The effects of noradrenaline (Nor) and phenylephrine (Phe) on the isolated, non-precontracted perforating branch of the human internal mammary artery (HIMA) were investigated. Nor and Phe induced concentration-dependent contractions of intact and endothelium-denuded arterial rings with no statistically significant differences between the pEC(30) and maximal response values. The pretreatment of arterial rings with indomethacin had no effect on Nor- and Phe-induced contractions of both, intact and endothelium-denuded preparations. The pre-addition of L-NMMA did not affect contractions of perforating branch of the HIMA evoked by Nor, but provoked significant potentiation of Phe-induced contractions of perforating branch of the HIMA both intact and denuded of endothelium only at Phe concentration higher than 3 x 10(-6)M. The effects of selective alpha1-adrenoceptor antagonist, prazosin and selective alpha2-adrenoceptor antagonist, rauwolscine were concentration-dependent, and they induced a significant shift to the right (for both studied antagonists) of the concentration-response curves for Nor in both preparations with or without endothelium. The effects of prazosin and rauwolscine on the concentration-response curves for Phe were similar. In conclusion, this study has shown that Nor and Phe induce concentration-dependent contractions of the perforating branch of the HIMA. Removal of the endothelium did not modify this effect. Products of cyclooxygenase pathway had no influence on Nor and Phe action. Endothelium derived nitric oxide (NO) had no modulatory effect of Nor-induced contractions, but inhibition of NO synthesis provoked potentiation of Phe-induced contractions either in intact or endothelium-denuded preparations. The mechanism of this effect remains still unclear. On the basis of differential affinity of the antagonists and affinities of Nor and Phe themselves, we suggest that alpha1-adrenoceptor subtype is probably involved in the Nor- and Phe-induced contraction of the perforating branch of the HIMA both intact or denuded of endothelium.

The rise in alveolar oxygen tension (PO(2)) that occurs as the newborn infant takes its first breaths induces removal of liquid from the lung lumen due to ion transport across the alveolar epithelium and the activity of alveolar Na(+) channel (ENaC). In the present study, we have aimed to identify an ion conductance in alveolar epithelial A549 cells that responds to acute changes in PO(2). Variation in PO(2) did not affect single-channel ENaC activity. However, in these cells we have detected single-channel conductance having properties similar to those of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels. Reverse transcriptase-polymerase chain reaction and Western blotting demonstrated presence of alpha-BKCa channel subunit and iberiotoxin, a blocker of BK(Ca) channels, inhibited whole cell K(+) current. Chronic changes in PO(2) did not affect expression, recruitment, or function of BK(Ca) channels in A549 cells. In contrast, acute changes of PO(2) regulated the BK(Ca) channel activity by controlling the channel mean open time. This effect of PO(2) was insensitive to inhibitor of flavoproteins, diphenylene iodinium. In addition, decrease in PO(2) and iberiotoxin induced membrane depolarization and Ca(2+) oscillations in A549 cells. We conclude that BK(Ca) channels serve as oxygen sensors in human alveolar A549 epithelial cells.

ATP-sensitive K(+) (K(ATP)) channels in the heart are normally closed by high intracellular ATP, but are activated during ischemia to promote cellular survival. These channels are heteromultimers composed of Kir6.2 subunit, an inwardly rectifying K(+) channel core, and SUR2A, a regulatory subunit implicated in ligand-dependent regulation of channel gating. Here, we have shown that the muscle form (M-LDH), but not heart form (H-LDH), of lactate dehydrogenase is directly physically associated with the sarcolemmal K(ATP) channel by interacting with the Kir6.2 subunit via its N-terminus and with the SUR2A subunit via its C-terminus. The species of LDH bound to the channel regulated the channel activity despite millimolar concentration of intracellular ATP. The presence of M-LDH in the channel protein complex was required for opening of K(ATP) channels during ischemia and ischemia-resistant cellular phenotype. We conclude that M-LDH is an integral part of the sarcolemmal K(ATP) channel protein complex in vivo, where, by virtue of its catalytic activity, it couples the metabolic status of the cell with the K(ATP) channels activity that is essential for cell protection against ischemia.