Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial

Aim

To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects.

Methods

The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery.

Results

Tramadol group had significantly lower pain scores (P = 0.005), significantly longer time to the first request for analgesic (P = 0.001), significantly shorter time to the beginning of liquid regimen (P = 0.001), and lower hemodynamic parameters such as blood pressure (P = 0.001) and heart rate (P = 0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting.

Conclusion

Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects.Registration No: IRCT201103255764N2Postoperative pain has not only a pathophysiologic impact but also affects the quality of patients’ lives. Improved pain management might therefore speed up recovery and rehabilitation and consequently decrease the time of hospitalization (1). Surgery causes tissue damage and subsequent release of biochemical agents such as prostaglandins and histamine. These agents can then stimulate nociceptors, which will send the pain message to the central nervous system to generate the sensation of pain (2-4). Neuroendocrine responses to pain can also cause hypercoagulation state and immune suppression, leading to hypoglycemia, which can delay wound healing (5).Tonsillectomy is a common surgery in children and post-tonsillectomy pain is an important concern. Duration and severity of pain depend on the surgical technique, antibiotic and corticosteroid use, preemptive and postoperative pain management, and patient’s perception of pain (6-9). There are many studies that investigated the control of post tonsillectomy pain using different drugs such as intravenous opioids, non-steroidal anti-inflammatory drugs, steroids, ketamine, as well as peritonsillar injection of local anesthetic, opioid, and ketamine (6,7,10-14).Ketamine is an intravenous anesthetic from phencyclidin family, which because of its antagonist effects on N methyl-D-aspartate receptors (that are involved in central pain sensitization) has regulatory influence on central sensitization and opium resistance. It can also band with mu receptors in the spinal cord and brain and cause analgesia. Ketamine can be utilized intravenously, intramuscularly, epidurally, rectally, and nasaly (15,16). Several studies have shown the effects of sub-analgesic doses of ketamine on postoperative pain and opioid consumption (7,13,15-17). Its side effects are hallucination, delirium, agitation, nausea, vomiting, airways hyper-secretion, and increased intra cerebral pressure and intra ocular pressure (10,11,15,16).Tramadol is an opium agonist that mostly effects mu receptors, and in smaller extent kappa and sigma receptors, and like anti depressant drugs can inhibit serotonin and norepinephrine reuptake and cause analgesia (6,12,18). Its potency is 5 times lower than morphine (6,12), but it has lower risk of dependency and respiratory depression, without any reported serious toxicity (6,12). However, it has some side effects such as nausea, vomiting, dizziness, sweating, anaphylactic reactions, and increased intra-cerebral pressure. It can also lower the seizure threshold (6,12,18,19).Several studies have confirmed the efficacy of tramadol and ketamine on post-tonsillectomy pain (6,10-12,20). In previous studies, effects of peritonsillar/ IV or IM infiltration of tramadol and ketamine were compared to each other and to placebo, and ketamine and tramadol were suggested as appropriate drugs for pain management (6,7,10-19,21). Therefore, in this study we directly compared the effect of peritonsillar infiltration of either tramadol or ketamine with each other and with placebo.     

Psychiatric heredity and posttraumatic stress disorder: survey study of war veterans

Aim

To explore the prevalence of psychiatric heredity (family history of psychiatric illness, alcohol dependence disorder, and suicidality) and its association with the diagnosis of stress-related disorders in Croatian war veterans established during psychiatric examination.

Methods

The study included 415 war veterans who were psychiatrically assessed and diagnosed by the same psychiatrist during an expert examination conducted for the purposes of compensation seeking. Data were collected by a structured diagnostic procedure.

Results

There was no significant correlation between psychiatric heredity of psychiatric illness, alcohol dependence, or suicidality and diagnosis of posttraumatic stress disorder (PTSD) or PTSD with psychiatric comorbidity. Diagnoses of psychosis or psychosis with comorbidity significantly correlated with psychiatric heredity (φ = 0.111; P = 0.023). There was a statistically significant correlation between maternal psychiatric illness and the patients’ diagnoses of partial PTSD or partial PTSD with comorbidity (φ = 0.104; P = 0.035) and psychosis or psychosis with comorbidity (φ = 0.113; P = 0.022); paternal psychiatric illness and the patients’ diagnoses of psychosis or psychosis with comorbidity (φ = 0.130; P = 0.008), alcohol dependence or alcohol dependence with comorbidity (φ = 0.166; P = 0.001); psychiatric illness in the primary family with the patients’ psychosis or psychosis with comorbidity (φ = 0.115; P = 0.019); alcohol dependence in the primary family with the patients’ personality disorder or personality disorder with comorbidity (φ = 0.099; P = 0.044); and suicidality in the primary family and a diagnosis of personality disorder or personality disorder with comorbidity (φ = 0.128; P = 0.009).

Conclusion

The study confirmed that parental and familial positive history of psychiatric disorders puts the individual at higher risk for developing psychiatric illness or alcohol or drug dependence disorder. Psychiatric heredity might not be necessary for the individual who was exposed to severe combat-related events to develop symptoms of PTSD.There are several risk factors associated with the development of posttraumatic stress disorder (PTSD), such as factors related to cognitive and biological systems and genetic and familial risk (1), environmental and demographic factors (2), and personality and psychiatric anamnesis (3).They are usually grouped into three categories: factors that preceded the exposure to trauma or pre-trauma factors; factors associated with trauma exposure itself; and post-trauma factors that are associated with the recovery environment (2,4).There are many studies which support the hypothesis that pre-trauma factors, such as ongoing life stress, psychiatric history, female sex (3), childhood abuse, low economic status, lack of education, low intelligence, lack of social support (5), belonging to racial and ethnic minority, previous traumatic events, psychiatric heredity, and a history of perceived life threat, influence the development of stress related disorders (6). Many findings suggest that ongoing life stress or prior trauma history sensitizes a person to a new stressor (2,7-9). The same is true for the lack of social support, particularly the loss of support from significant others (2,9-11), as well as from friends and community (12-14). If the community does not have an elaborated plan for providing socioeconomic support to the victims, then the low socioeconomic status can also be an important predictor of a psychological outcome such as PTSD (2,10,15). Unemployment was recognized as a risk factor for developing PTSD in a survey of 374 trauma survivors (16). It is known that PTSD commonly occurs in patients with a previous psychiatric history of mental disorders, such as affective disorders, other anxiety disorders, somatization, substance abuse, or dissociative disorders (17-21). Epidemiological studies showed that pre-existing psychiatric problems are one of the three factors that can predict the development of PTSD (2,22). Pre-existing anxiety disorders, somatoform disorders, and depressive disorders can significantly increase the risk of PTSD (23). Women have a higher vulnerability for PTSD than men if they experienced sexually motivated violence or had pre-existing anxiety disorders (23,24). A number of studies have examined the effects of gender differences on the predisposition for developing PTSD, with the explanation that women generally have higher rates of depression and anxiety disorders (3,25,26). War-zone stressors were described as more important for PTSD in men, whereas post-trauma resilience-recovery factors as more important for women (27).Lower levels of education and poorer cognitive abilities also appear to be risk factors (25). Golier et al (25) reported that low levels of education and low IQ were associated with poorer recall on words memorization tasks. In addition, this study found that the PTSD group with lower Wechsler Adult Intelligence Scale-Revised (WAIS-R) scores had fewer years of education (25). Nevertheless, some experts provided evidence for poorer cognitive ability in PTSD patients as a result or consequence rather than the cause of stress-related symptoms (28-31). Studies of war veterans showed that belonging to racial and ethnic minority could influence higher rates of developing PTSD even after the adjustment for combat exposure (32,33). Many findings suggest that early trauma in childhood, such as physical or sexual abuse or even neglect, can be associated with adult psychopathology and lead to the development of PTSD (2,5,26,34,35). Surveys on animal models confirm the findings of lifelong influences of early experience on stress hormone reactivity (36).Along with the reports on the effects of childhood adversity as a risk factor for the later development of PTSD, there is also evidence for the influence of previous exposure to trauma related events on PTSD (9,26,28). Breslau et al (36) reported that previous trauma experience substantially increased the risk for chronic PTSD.Perceived life threats and coping strategies carry a high risk for developing PTSD (9,26). For instance, Ozer et al (9) reported that dissociation during trauma exposure has high predictive value for later development of PTSD. Along with that, the way in which people process and interpret perceived threats has a great impact on the development or maintenance of PTSD (37,38).Brewin et al (2) reported that individual and family psychiatric history had more uniform predictive effects than other risk factors. Still, this kind of influence has not been examined yet.Keeping in mind the lack of investigation of parental psychiatric heredity on the development of stress-related disorders, the aim of our study was to explore the prevalence and correlation between the heredity of psychiatric illness, alcohol dependence, suicidality, and the established diagnosis of stress-related disorders in Croatian 1991-1995 war veterans.     

Microcoagulation of junctional dorsal root entry zone is effective treatment of brachial plexus avulsion pain: long-term follow-up study

Aim

To analyze long-term clinical results of coagulation lesions of the dorsal root entry zone (DREZ) in patients with deafferentation pain due to brachial plexus avulsion and to correlate the pain relief after DREZ coagulation with pain duration before the DREZ coagulation.

Methods

Twenty-six patients with intractable deafferentation pain after brachial plexus avulsion lesion were treated for pain at the Department of Neurosurgery. Junctional coagulation lesion was made with bipolar forceps along the DREZ. The patients assessed post-operative analgesic effect using a visual analog scale at 1 week, 1 year, 3 years, and 5 years after the surgery.

Results

The greatest pain relief was reported immediately after the DREZ procedure. Over the 5-year follow-up period, the pain relief effect gradually and significantly decreased. There were no significant differences between the pain relief evaluated at 1 week and after 1 year and between the pain relief evaluated at 1 week and after 3 years. There was a correlation between the pain duration before the surgery and pain relief after the surgery, with best correlation found between pain duration before surgery and pain relief 5 years after DREZ procedure (r = 0.623, P = 0.007).

Conclusion

The long-term follow up showed that the pain relief gradually decreased over 5 years after surgery. However, the pain relief still did not significantly decrease after 3 years.There is experimental and clinical evidence that pain generators in brachial plexus avulsion are at least partially located in the deafferented dorsal horn (1-3). The term deafferentation pain has been defined as pain or dysesthesia caused by interruption of the peripheral or central afferent input in the central nervous system (4). When the large lemniscal afferents within peripheral nerves or dorsal roots are altered, the inhibitory control of the dorsal horn is reduced (5). It was suggested that dorsal horn deafferentation by cervical posterior rhizotomy in the rat provides a reliable model of chronic pain due to brachial plexus avulsion and that this deafferentation pain is successfully relieved by microsurgical dorsal root entry zone (DREZ) rhizotomy (6). Pain following brachial plexus avulsion is the most typical manifestation of the chronic deafferentation pain in humans (4). Preganglionic lesion of the dorsal horn of the cervical spinal cord due to root avulsion may lead to important pathological changes responsible for the induction of pain sensations in 90% of the patients (7). Medications, neurostimulation techniques, and various ablative surgical procedures other than DREZ surgery, including cervical anterolateral cordotomy, mesencephalic spinothalamic tractotomy, and medial thalamotomy, have not shown long-term efficacy and are not exempt from disabling side effects (8,9). On the contrary, the neurosurgical procedure of coagulation lesions in the DREZ has been shown effective in pain relief after brachial plexus avulsion (10-16). The DREZ was chosen as a possible neurosurgical target to stop abnormal firing of impulses, which most probably originate in the central portion of the dorsal nerve roots, in Lissauer’s tracts and Rexed’s laminas I-V of the dorsal horn. The idea of a DREZ lesion was put forward in 1972 (17,18) and 4 years later, it was accepted as a useful pain-relieving therapeutic procedure (7). The aim of DREZ lesioning is the treatment of neuropathic pain associated with dysfunction in the gating circuitry of the dorsal horn and generated by dorsal horn hyperactive neurons (1,5). The original procedure in the DREZ region, which includes series of focal radiofrequency heat lesions 2-3 mm apart along the line of the posterolateral fissure at the site of the avulsion of the rootlets (7,19), has been updated by Rawlings et al (20). A series of DREZ lesions may also be produced with microsurgical lasers (21-23). Dreval (24) reported on ultrasonic DREZ operation for the treatment of pain due to brachial plexus avulsion. Computer-assisted DREZ microcoagulation for posttraumatic spinal deafferentation pain is described by Edgar et al (25). In our previous study, we described our experience and clinical results of microsurgical junctional DREZ coagulation performed for pain relied in different deafferentation syndromes (26). Since the DREZ procedures are the most effective in the treatment of pain, particularly brachial plexus avulsion pain, and the good results have tendency to diminish with time, the studies to analyze the long-term effects of the procedure on pain after brachial plexus avulsion are needed.The aim of the study was to determine long-term clinical results of the DREZ coagulation lesion, primarily the duration and degree of pain relief, in patients with deafferentation pain due to brachial plexus avulsion.     

Heterogeneity of posttraumatic stress disorder symptoms in Croatian war veterans: retrospective study

Aim

To determine the relationship between the intensity of combat-related posttraumatic stress disorder (PTSD) and the intensity of predominating symptoms.

Method

The study included 151 veterans from 1992-1995 war in Croatia with PTSD, aged 38.3 ± 7.3 years (mean ± standard deviation). The veterans were psychologically tested with the Mississippi Scale for Combat-related PTSD (M-PTSD), Questionnaire on Traumatic Combat and War Experiences (USTBI-M), and Minnesota Multiphasic Personality Inventory-version 201 (MMPI-201).

Results

The discriminative analysis of the data revealed that the group with lower PTSD intensity had the highest scores on MMPI scales D (depression, T-score 95.7 ± 5.6), Hs (hypochondriasis, 87.6 ± 5.1), and Hy (hysteria, 85.6 ± 4.9), whereas the group with higher PTSD intensity, besides these three scales (D = 98.3 ± 5.3; Hs = 90.1 ± 4.3; Hy = 89.5 ± 4.7), also had clinically significantly elevated Pt (psychastenia, 80.6 ± 5.6), Sc (schizophrenia, 79.6 ± 4.8), and Pa (paranoia, 85.6 ± 5.4) scales, with the highest Pa scale.

Conclusion

It was possible to differentiate study participants with different PTSD intensity on the basis of their MMPI profile. More intense PTSD was associated with externalized symptoms, such as aggression, acting-out, hostility, and mistrust, whereas less intensive PTSD was associated with mostly depressive symptoms. Our study showed that different intensity of PTSD has different symptom patterns.A person’s reaction to trauma depends on the traumatic situation itself, personality characteristics of the person exposed to trauma, and posttraumatic social environment. Most people develop some form of acute stress reaction to traumatic event, but in the majority of cases the stress-related difficulties spontaneously withdraw once the person is removed from the situation (1). Fewer people will develop chronic disorders which may evolve into a clinical picture of posttraumatic stress disorder (PTSD) (2). Symptoms that characterize PTSD include repeated re-experiencing of the trauma, emotional numbing, detachment, lack of affect, anhedonia, and avoidance of activities and situations reminiscent of the traumatic event (3).PTSD is often comorbid with other psychiatric disorders (4-7). Patients with PTSD often complain of psychosomatic disturbances, ranging from anxiety accompanied with tremor and restlessness to depressive problems with predominant cognitive aspects of depression (dark thoughts, shame, guilt, and suicidal thoughts and intentions) and to vegetative symptoms (insomnia and loss of appetite) (8). Comorbidity of PTSD with anxiety or depressive disorders is diagnosed in cases where anxiety or depressive symptoms are prevalent. Due to these psychiatric problems, patients with PTSD often resort to alcohol or drug abuse (4). Memory and concentration impairment, often present in PTSD, may seriously interfere with everyday functioning of these patients (9).Because PTSD symptoms are so heterogeneous, many researchers presume that there are different subtypes of the disorder. Previous attempts to determine different types of PTSD used different methodologic approaches (10-12). Some studies analyzed characteristics of PTSD with respect to predominant symptomatology (6,8), whereas others tried to associate PTSD symptoms with different types of stressors (12,13). Electrophysiological indicators of PTSD as well as the possibility to determine different types of PTSD on the basis of specific electrophysiological indicators were investigated (14,15).Further attempts to discern among different types of PTSD were based on personality tests, primarily Minnesota Multiphasic Personality Inventory (MMPI) (16), response to specific pharmacotherapy (17), and existing aggressive behavior (18-20). Recently, intensity of PTSD has been investigated as a factor that determines the type of the disorder (21-23).The aim of the present study was to determine the relationship between the intensity of PTSD and predominating symptoms in a sample of Croatian 1991-1995 war veterans.     

Blood lactate levels in patients receiving first- or second- generation antipsychotics

Aim

To compare the blood lactate levels between patients with psychotic disorder receiving first- and those receiving second-generation antipsychotics.

Methods

The study was conducted at the psychiatric inpatient and outpatient clinics of the Split Clinical Hospital from June 6, 2008 to October 10, 2009. Sixty patients with psychotic disorder who were assigned to 6-month treatment were divided in two groups: 30 received haloperidol (first generation antipsychotic) and 30 received olanzapine (second generation antipsychotic). Blood lactate levels, other metabolic parameters, and scores on the extrapyramidal symptom rating scale were assessed.

Results

Patients receiving haloperidol had significantly higher blood lactate levels than patients receiving olanzapine (P < 0.001). They also more frequently had parkinsonism, which was significantly correlated with both haloperidol treatment at 1 month (P < 0.001) and 6 months (P = 0.016) and olanzapine treatment at baseline (P = 0.016), 3 months (P = 0.019), and 6 months (P = 0.021). Also, patients receiving haloperidol had significant correlation between blood lactate and dystonia at 1 month (P < 0.001) and 6 months (P = 0.012) and tardive dyskinesia at 1 month (P = 0.032). There was a significant difference between the treatment groups in lactate levels at all points from baseline to month 6 (P < 0.001).

Conclusion

It is important to be aware of the potential effect of haloperidol treatment on increase in blood lactate levels and occurrence of extrapyramidal side effects. Therefore, alternative antipsychotics should be prescribed with lower risk of adverse side effects.

Trial identification number

NCT01139463Due to their heterogeneity, antipsychotics are difficult to classify, but they are frequently categorized as the first- and second-generation based on the incidence of extrapyramidal side effects, ie, antidopaminergic activity (1,2). First-generation antipsychotics have dominant antidopaminergic activity and pronounced extrapyramidal side effects (1), while second-generation antipsychotics have a pronounced effect on other neurotransmitter systems, as well as sporadic extrapyramidal side effects.Antipsychotics block numerous neurotransmitter receptors in a manner that induces therapeutic effects and side effects, which may vary in intensity and produce serious consequences (3-7). Extrapyramidal side effects (adverse cardiovascular, hematological, gastrointestinal, sexual, and urologic effects) are most frequently manifested in first-generation antipsychotics due to their non-selective dopaminergic block (1,8-10). The consequence of a dopaminergic effect on the tuberoinfundibular system causing dopamine to inhibit prolactin secretion is hyperprolactinemia (11,12), with possible consequences such as tissue hypoxia and mortality (13-15).Particular attention today is paid to the effects of first-generation antipsychotics on metabolic disorders. Numerous studies have shown that first-generation antipsychotic therapy may lead to metabolic changes, particularly changes in the regulation of glucose, lipid levels, and body weight (3-5,13-21). These side effects are associated with increased mortality and substantial morbidity including diabetes, hypertension, and cardiovascular disease (22,23). In many years of clinical practice, we have empirically observed that treatment with certain antipsychotics causes, along with recognized and described metabolic disorders, an increase in the blood lactate levels. Increased lactate levels are generally associated with increased morbidity and mortality in patients with chronic illnesses or critically ill patients (13,14,24-26). A review of the literature did not find any studies on the effect of antipsychotic therapy on lactate levels or such changes as a part of other antipsychotic side effects. Therefore, it is important to investigate this phenomenon in patients taking first- or second-generation antipsychotic medication.We hypothesized that a 6-month treatment with haloperidol or olanzapine would change blood lactate levels and cause extrapyramidal side effects in patients without prior antipsychotic treatment.     

Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study

Aim

To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence.

Methods

In this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them.

Results

HALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n = 4) was significantly higher (P < 0.001) than among the remaining reports (580 out of 1982; n = 2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter.

Conclusion

The study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education.Adverse drug reactions (ADR) are among the leading causes of mortality and morbidity responsible for causing additional complications (1,2) and longer hospital stays. Magnitude of ADRs and the burden they place on health care system are considerable (3-6) yet preventable public health problems (7) if we take into consideration that an important cause of ADRs are drug-drug interactions (8,9). Although there is a substantial body of literature on ADRs caused by drug-drug interactions, it is difficult to accurately estimate their incidence, mainly because of different study designs, populations, frequency measures, and classification systems (10-15).Many studies including different groups of patients found the percentage of potential drug-drug interactions resulting in ADRs to be from 0%-60% (10,11,16-25). System analysis of ADRs showed that drug-drug interactions represented 3%-5% of all in-hospital medication errors (3). The most endangered groups were elderly and polimedicated patients (22,26-28), and emergency department visits were a frequent result (29). Although the overall incidence of ADRs caused by drug-drug interactions is modest (11-13,15,29,30), they are severe and in most cases lead to hospitalization (31,32).Potential drug-drug interactions are defined on the basis of on retrospective chart reviews and actual drug-drug interactions are defined on the basis of clinical evidence, ie, they are confirmed by laboratory tests or symptoms (33). The frequency of potential interactions is higher than that of actual interactions, resulting in large discrepancies among study findings (24).A valuable resource for detecting drug-drug interactions is a spontaneous reporting database (15,34). It currently uses several methods to detect possible drug-drug interactions (15,29,35,36). However, drug-drug interactions in general are rarely reported and information about the ADRs due to drug-drug interactions is usually lacking.The aim of this study was to estimate the incidence of actual and potential drug-drug interactions in the national Spontaneous Reporting Database of ADRs in Croatia. Additionally, we assessed the clinical significance and seriousness of drug-drug interactions and their probable mechanism of action.     

Circulating lymphocyte subsets, natural killer cell cytotoxicity, and components of hypothalamic-pituitary-adrenal axis in Croatian war veterans with posttraumatic stress disorder: cross-sectional study

Aim

To determine peripheral blood lymphocyte subsets – T cells, helper T cells, cytotoxic T cells, B cells, and natural killer cells, natural killer cell cytotoxicity, serum cortisol concentration, and lymphocyte glucocorticoid receptor expression in Croatian combat veterans diagnosed with chronic posttraumatic stress disorder (PTSD); and to examine the relationship between the assessed parameters and the time passed since the traumatic experience.

Methods

Well-characterized group of 38 PTSD patients was compared to a group of 24 healthy civilians. Simultaneous determination of lymphocyte subsets and the expression of intracellular glucocorticoid receptor was performed using three-color flow cytometry. Natural killer cell cytotoxicity was measured by ⁵¹Cr-release assay and the serum cortisol concentration was determined by radioimmunoassay.

Results

We found higher lymphocyte counts in PTSD patients than in healthy controls (2294.7 ± 678.0/μL vs 1817.2 ± 637.0/μL, P = 0.007) and a positive correlation between lymphocyte glucocorticoid receptor expression and the number of years that passed from the traumatic experience (r_s = 0.43, P = 0.008). Lymphocyte glucocorticoid receptor expression positively correlated with serum cortisol concentration both in PTSD patients (r = 0.46, P = 0.006) and healthy controls (r = 0.46, P = 0.035).

Conclusion

This study confirmed that the immune system was affected in the course of chronic PTSD. Our findings also indicated that the hypothalamic-pituitary-adrenal axis profile in PTSD was associated with the duration of the disorder. Due to the lack of power, greater sample sizes are needed to confirm the results of this study.Prolonged or frequently repeated stress response during symptomatic episodes in chronic posttraumatic stress disorder (PTSD) can result in neuroendocrine and immune alterations, posing serious threat to mental and physical health (1,2). Evidence suggests that PTSD is related to increased medical morbidity, particularly from cardiovascular and autoimmune diseases (3). With controversial findings when neurobiology of PTSD is concerned, the patophysiological mechanisms underlying increased susceptibility to disease are not clear (4,5). However, it has been implicated that the sympathetic-adrenal-medullary (SAM) and the hypothalamic-pituitary-adrenal axes are the key mediators in this process (6,7).The immune system interacts with the hypothalamic-pituitary-adrenal axis in a bidirectional fashion to maintain homeostasis. Being the primary effector of the stress response, cortisol modifies the complex cytokine network and, consequently, leukocyte function and recirculation (8). These effects are achieved through its interaction with the specific intracellular glucocorticoid receptors (9).Studies of the leukocyte recirculation (10,11), immune cells function (12), and hypothalamic-pituitary-adrenal axis activity (5) in PTSD yielded controversial results. Overall findings support the hypothesis that immune activation in PTSD may be associated with Th2 cytokine shift and alterations in the proinflammatory cytokine system (4). Besides, it is believed that PTSD is linked with low plasma cortisol levels and higher glucocorticoid receptor expression, suggesting enhanced feedback sensitivity to cortisol (13). In contrast to these findings, Gotovac et al (14) showed that Croatian combat veterans with PTSD, approximately 6 years after traumatic event, had lower expression of glucocorticoid receptor in lymphocyte subsets, with higher serum cortisol concentration than healthy subjects. Majority of other studies did not take into account the time passed since the trauma and their samples mainly included Vietnam veterans (15) or Holocaust survivors (16), who had greater time gap since the traumatic experience than Croatian war veterans.Considering the strong discrepancies in the results published to date, we performed a cross-sectional study to evaluate the correlation between PTSD in Croatian combat war veterans and the percentages of circulating lymphocyte subsets, natural killer cell cytotoxicity as a measure of immune function, and the serum cortisol concentration with lymphocyte glucocorticoid receptor expression as components of hypothalamic-pituitary-adrenal axis. The emphasis was put on the relationship between the assessed parameters and the time passed since the traumatic experience.     

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.     

Levels of self-reported depression and anxiety among HIV-positive patients in Albania: a cross-sectional study

Aim

To gain an initial perspective of mental health issues facing the Human Immunodeficiency Virus (HIV)-positive population at the University Hospital Center of Tirana (UHCT) HIV/AIDS Ambulatory Clinic.

Methods

From June-August 2009, we conducted semi-structured interviews with 79 patients (93% response rate) at the UHCT HIV/AIDS Ambulatory Clinic. The interviews assessed patient-reported histories of mental health diagnoses, patients’ demographics, and current emotional health status.

Results

The percentage of patients who reported a history of diagnosis of depression or anxiety was high – 62.3% and 82.3%, respectively. Factors associated with a history of depression included having been diagnosed with anxiety (P < 0.001), having a higher number of barriers to care (P < 0.001), having a higher number of current medical and social needs (P < 0.001), or having not obtained antiretroviral therapy (ART) abroad (P = 0.004). Factors associated with a history of anxiety included having been on first-line ART (P = 0.008), having been diagnosed with HIV for shorter periods of time (P = 0.043), having been diagnosed with depression (P < 0.001), having a higher number of current medical and social needs (P = 0.035), or having not obtained ART abroad (P = 0.003).

Conclusions

Mental health problems are widespread among the known HIV-positive patient population in Albania. The high prevalences of anxiety and depression and of dual diagnoses of these conditions suggest the need for more mental health care for HIV-positive patients in Albania.Mental health is one of the co-morbidities that is often overlooked in treating patients for Acquired Immune Deficiency Syndrome from Human Immunodeficiency Virus (HIV/AIDS) (1-3). In particular, the rates of depression and anxiety are higher than those in the general population (1-6). Depression is second only to substance abuse as the most prevalent psychiatric disorder among HIV-positive patients (5). In the context of HIV/AIDS, depression has also been shown to lead to more social isolation, lower antiretroviral medication adherence, and faster progression to AIDS (7-14). Anxiety, especially among those that have recently been diagnosed with HIV, has been shown to be more prevalent among patients with stress or excess social stigma related to their diagnosis (15-17). Anxiety can also correlate with lower adherence to antiretroviral therapy (ART) and medical recommendations (18,19).With mental health issues affecting medical treatment of HIV, mechanisms to reduce their burden among HIV-positive patients have been explored. Treatment of depression has been shown to improve adherence to ART along with the quality of life for HIV-positive patients (5,20,21). Community-based group therapy has also been shown to decrease psychiatric symptoms in HIV-positive patients or in regions with high prevalence of HIV, while treatment with ART may reduce both anxiety and depression (22,23). However, with all the advances in the field of mental health, there is still a paucity of data from developing countries (especially Eastern and Central Europe) on the relationship between HIV/AIDS and mental health (18).With the growing epidemic of HIV in Eastern Europe and possible spread to South Eastern Europe, an understanding of the mental health issues facing HIV-positive patients will be vital for the improvement of medical services and treatment for HIV (18,24-29). This is especially true in countries that have only recently initiated psychological services for HIV positive patients. Albania, which boasts a low prevalence of HIV, is one such country that initiated psychological services soon after the introduction of ART in 2004 (30,31). High levels of risky behavioral patterns (including low condom usage and high rates of needle sharing among injection drug users), the recent sociopolitical changes, and the under-resourced prevention and surveillance capabilities, have placed the Albanian population at risk for a rising local HIV epidemic (30-34). In fact, previous studies have suggested that the prevalence of HIV in Albania may be 150-fold the current Ministry of Health estimate (35,36). Thus, an initial patient-driven assessment of the mental health issues of patients under HIV/AIDS medical care in Albania is warranted. In this study, we examined the prevalence of HIV-positive patients’ self-reported histories of mental health diagnoses in Albania. This study also examined effects of ART on mental health and associations with depression and anxiety.     

Regional differences in incidence and clinical presentation of type 1 diabetes in children aged under 15 years in Croatia

Aim

To determine regional differences in the incidence, incidence trends, and clinical presentation of type 1 diabetes in children under the age of 15 years in Croatia in a 9-year period (1995-2003).

Methods

We included the patients who had been diagnosed with the disease and had started the insulin treatment before they were 15 years old. Regional differences between eastern, central, and southern Croatia were observed. The gross incidence was expressed by the number of newly diagnosed type 1 diabetes patients in 100 000 children of the same age and sex per year, ie, for the 0-14 age group, and for the 0-4, 5-9, and 10-14 subgroups.

Results

The highest incidence was observed in southern Croatia (10.91 per 100 000/y) and the lowest in central Croatia (8.64 per 100 000/y), and in eastern Croatia the incidence was 8.93 per 100 000/y. All three regions showed a growing incidence trend, which was significant only in eastern and southern Croatia. There was 35.9% of patients with diabetic ketoacidosis in eastern Croatia, 41.7% in central Croatia, and 31.3% in southern Croatia.

Conclusion

Croatian regions show differences in the incidence, incidence trends, and disease presentation of type 1 diabetes. A further follow-up is needed to establish whether the regional differences are a consequence of the population dynamics in the observed period or they will continue to exist, pointing to differences in environmental risk factors.The incidence of type 1 diabetes is highest in Finland, amounting to 40.9/100 000/y, and lowest in China and Venezuela, amounting to 0.1/100 000/y (1). It varies up to by 10 times among European countries, and as much as by 400 times globally (2). These variations are mainly caused by differences in the genetic makeup of specific ethnic groups and diverse environmental factors (3,4).Sometimes countries of a certain region have similar incidence patterns despite their genetic and long-standing socio-economic differences. A good example are Hungary (7.87/100 000/y), Austria (9.5/100 000/y), the Czech Republic (9.8/100 000/y), and Slovakia (9.2/100 000/y) (5,6). In contrast to this, certain bordering countries sharing the same genetic pool show considerable differences in their incidence rates, ie, Spain and Portugal, and Finland and the Russian province Karelia (7,8). Such cases have not only been recorded in Europe, but also in America. While the incidence for Puerto Rico is the same as for the majority of the US states (17/100 000/y), the neighboring Cuba has a considerably lower incidence, with fewer than 3 patients per 100 000/y (9).Differences in the incidence rates have been recorded even among the regions of the same country (5,10-14). In some cases, this may be explained by the presence of a certain ethnic minority (14) with a different genetic base than the majority population. However, variations are sometimes noted in genetically more homogeneous populations, which points to environmental factors as the possible cause of the differences (10,11). Some studies have shown that changes in the incidence in different regions do not necessarily follow the same pattern over a course of time (15).Establishing the regional distribution of a disease is an important epidemiological method, which may lead to certain etiological hypotheses (10). Since the national incidence and clinical presentation patterns of type 1 diabetes in Croatia had already been established (16,17), the aim of this study was to determine regional differences in the incidence, incidence trends, and clinical presentation of type 1 diabetes in children under the age of 15 years within a 9-year period.     

Relation between burnout syndrome and job satisfaction among mental health workers

Aim

To identify predictors of burnout syndrome, such as job satisfaction and manifestations of occupational stress, in mental health workers.

Method

The study included a snowball sample of 174 mental health workers in Croatia. The following measurement instruments were used: Maslach Burnout Inventory, Manifestations of Occupational Stress Survey, and Job Satisfaction Survey. We correlated dimensions of burnout syndrome with job satisfaction and manifestations of occupational stress dimensions. We also performed multiple regression analysis using three dimensions of burnout syndrome – emotional exhaustion, depersonalization, and personal accomplishment.

Results

Stepwise multiple regression analysis showed that pay and rewards satisfaction (β = -0.37), work climate (β = -0.18), advancement opportunities (β = 0.17), the degree of psychological (β = 0.41), and physical manifestations of occupational stress (β = 0.29) were significant predictors of emotional exhaustion (R = 0.76; F = 30.02; P<0.001). The frequency of negative emotional and behavioral reactions toward patients and colleagues (β = 0.48), psychological (β = 0.27) and physical manifestations of occupational stress (β = 0.24), and pay and rewards satisfaction (β = 0.22) were significant predictors of depersonalization (R = 0.57; F = 13.01; P<0.001). Satisfaction with the work climate (β = -0.20) was a significant predictor of lower levels of personal accomplishment (R = 0.20; F = 5.06; P<0.005).

Conclusion

Mental health workers exhibited a moderate degree of burnout syndrome, but there were no significant differences regarding their occupation. Generally, both dimensions of job satisfaction and manifestations of occupational stress proved to be relevant predictors of burnout syndrome.Burnout syndrome is a subject of the interdisciplinary area of occupational stress research (1). It is defined as a sustained response to chronic work stress and includes emotional exhaustion, negative attitudes, and feelings toward the recipients of the service (depersonalization), and a feeling of low accomplishment and professional failure. Emotional exhaustion involves feelings of being emotionally overextended and exhausted by one’s work, resulting in a loss of energy and general weakness. Depersonalization refers to the development of impersonal and unfeeling attitudes toward patients and loss of idealism at work. The feeling of reduced personal accomplishment refers to a feeling of lack of competence and personal achievement (2).Burnout syndrome was most often studied among helping professionals (nurses, physicians, psychologists, and social workers), education, and human resources professionals (3,4). In mental health workers, sources of occupational stress are mostly related to the difficulties in the functioning of health care system (5,6), such as time pressure, chronic fatigue, uncertainties in patient care, demanding chronic patients, poor interpersonal relations at work, and role ambiguity (7-9). Moreover, working with patients is considered to be one of the most important factors leading to burnout syndrome (6,10).In the 1990, in Croatia, a number of studies was conducted on the occupational stress in the helping profession (1,11,12) and burnout syndrome (2,13-16), showing their negative effect on the workers’ health and economic losses induced by absence from work and decreased working productivity. Also, some recent studies have identified personal, interpersonal, and organization factors related to job satisfaction, occupational stress, and burnout syndrome in health care (17-21) and have confirmed a correlation between low job satisfaction and burnout syndrome (22,23).Low job satisfaction can lead to increased job mobility and more frequent absenteeism, which may reduce the efficiency of health care services (24). In the previous research (25), the relationship between job satisfaction and burnout syndrome was viewed from two perspectives – the perspective of causes and the perspective of consequences and their effect on attitudes, mental and physical health, productivity, absence from work, fluctuation, and other different forms of work behavior. Some of recent studies have shown that social workers (26-28) and nurses (29) express lower job satisfaction than other professions in mental health care.Low job satisfaction among mental health workers has also been confirmed by some studies conducted in United Kingdom (30) and Canada (31), while several studies have shown exactly the opposite, ie, that there is a high degree of job satisfaction among employees in these professions (6,20,21). Exposure to occupational stress leads to psychological and physical reactions, the intensity and form of manifestation of which depends on personality traits and environmental factors. The most widespread manifestations of occupational stress in helping professions include emotional exhaustion, depersonalization and dehumanized perception of the patient, absenteeism, damaged physical health, and reduced personal satisfaction. Studies have shown that, compared with general population and other professions, social workers suffer from relatively high level of anxiety and depression related to their profession (32,33).The aims of this study were to examine the relation between burnout syndrome and job satisfaction and to identify independent predictors, such as job satisfaction and manifestations of occupational stress, of burnout syndrome among mental health workers.     

Changes in plasma lipid concentrations and risk of coronary artery disease in army veterans suffering from chronic posttraumatic stress disorder

Aim

To test the differences in serum lipid concentrations between veterans with chronic posttraumatic stress disorder (PTSD) and veterans without PTSD.

Methods

We determined plasma lipid parameters and calculated risk factors for 50 veterans in the PTSD group and 50 veterans in the non-PTSD group. Trauma exposure, coping strategies, and quality of life were assessed with Life Stressor List, Manchester Short Assessment of Quality of Life Scale, and Folkman-Lazarus Coping Strategies Questionnaire.

Results

There was no difference between the groups in the exposure to combat trauma. PTSD group had significantly lover education than non-PTSD group (10.6 ± 1.8 vs 12.4 ± 2.6 years, P = 0.007) and lower monthly income per family member (€67.8 ± 51.3 vs €281.9 ± 208.2, P < 0.001). PTSD group had significantly higher levels of all plasma lipid parameters (cholesterol: 6.54 ± 1.24 vs 5.40 ± 1.09 mmol/L, P < 0.001; triglycerides: 2.55 ± 0.68 vs 1.73 ± 0.77 mmol/L, P < 0.001; very low density lipoprotein-cholesterol: 1.14 ± 0.32 vs 0.78 ± 0.35 mmol/L, P < 0.001; low density lipoprotein-cholesterol: 4.49 ± 1.06 vs 3.46 ± 0.93 mmol/L, P < 0.001). High-density lipoprotein cholesterol concentration was significantly lower in PTSD group (0.96 ± 0.18 vs 1.15 ± 0.24 mmol/L, P < 0.001). Established risk factor for arteriosclerosis (6.96 ± 1.19 vs 4.71 ± 0.88, P < 0.001) and Adult Treatment Panel III ten years risk for coronary disease (19.44 ± 7.27% vs 9.74 ± 4.10%, P < 0.001) were significantly higher in the PTSD group. Secondary traumatization was significantly more frequent in the PTSD group (3.8 ± 5.7 vs 1.3 ± 4.7 events; P < 0.001).

Conclusions

Chronic PTSD is associated with dyslipidemia, leading to an increased risk of coronary artery disease. Environmental factors and coping strategies should be considered as important factors for the occurrence and persistence of PTSD.“The body keeps the score: memory and the evolving psychobiology of post traumatic stress” by Bessel van der Kolk (1) was published in the Harvard Review of Psychiatry in 1994. Although it may not be the first article on neurobiology of posttraumatic stress disorder (PTSD), the strong metaphor contained in the first part of its title summarizes the research results in this field. Studies looking for biological causes of a disorder that is clearly precipitated by environmental or man-made causes were largely outnumbered by studies on the psychosocial nature of the disorder decades after the delayed first recognition of PTSD in the diagnostic manuals – 1980 in Diagnostic and Statistical Manual of Mental Disorders III (DSM III) (2) and 1990 in the International Classification of Diseases-10 (ICD-10) (3). A small number of studies appeared in literature in parallel with the recognition of the disorder, but the number of biological studies since September 11, 2001 has grown 5-fold and keeps growing (4).Research interest mainly focused on alterations of neuroendocrine regulation (5,6) and neuroanatomical (7) and neuroimmunological alterations (8,9). From the neuroendocrine point of view, in PTSD there is an increased noradrenergic activity in absence of shutdown by serum cortisol that has been found to be decreased in this disorder due to dysregulation of the hypothalamo-pituitary-adrenal axis (10-12). Studies on changes in serum lipid concentrations were based on clinical observations and the results of epidemiological studies indicating increased cerebrovascular and cardiovascular morbidity and mortality in survivors of prolonged traumatic and combat stress (13-17). Kagan’s pioneer study (18) of changes in lipid status of Vietnam veterans was published in 1999 and was followed by the work of other researchers who confirmed its results (19-23).The population of Bosnia and Herzegovina suffered massive and prolonged traumatization in the 1992-1995 war (24-26). Increase in the prevalence and incidence of PTSD in comparison with the period before the war, as well as the increase in trauma-related disorders in overall psychiatric morbidity, represents a logical consequence of these events (27). In our work with people suffering from chronic PTSD, we had frequently noticed alterations of serum lipids, associated with an increased risk of cardiovascular diseases. This is consistent with our clinical observation of increased cardiovascular and cerebrovascular morbidity in patients who had been treated in the Unit for Trauma-related Disorders of the Department of Psychiatry of the University Clinical Center in Sarajevo and the literature (13-17). Therefore, we aimed to explore the differences in concentrations of serum cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), index of arteriosclerosis, established risk factor for arteriosclerosis (ERF), and 10 years-risk for coronary disease according to Adult Treatment Panel III (ATP III) (28) between veterans with the diagnosis of chronic PTSD and veterans without the diagnosis of PTSD. Our second aim was to compare and analyze the differences between the two groups in socio-demographic characteristics, trauma exposure measures, secondary traumatization (after the war), PTSD symptoms, coping strategies, and quality of life, to obtain information on the factors influencing the development and persistence of PTSD in veterans with combat stress exposure.There are divided opinions in literature whether this disorder develops in individuals with certain predisposing factors or all people have equal chances of developing PTSD (29-32). There is also a question whether biological markers of PTSD are trait markers or state markers, as well as whether PTSD can be explained by stress-diathesis model as schizophrenia (33). To explore these claims, we also compared socio-demographic characteristics of the sample, trauma events inventory, coping strategies, and quality of life indicators.     

Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule and interstitial cell apoptosis in rats

Aim

To investigate the effects of angiotensin-converting enzyme inhibitor (cilazapril) and angiotensin II type I receptor antagonist (losartan) on tubular and interstitial cell apoptosis and caspase-3 activity in rats with obstructive nephropathy after unilateral ureteral obstruction.

Methods

Rats with unilateral obstructive nephropathy and sham-operated rats were treated with cilazapril, losartan, or the vehicle (water). Tubular and interstitial cell apoptosis was detected morphologically on hematoxylin and eosin-stained renal specimens and by the terminal deoxynucleotidyl transferase-mediated nick end-labeling. Caspase-3 activity in whole-kidney tissue homogenates was measured colorimetrically.

Results

After unilateral ureter ligation, there was a significant increase in the number of apoptotic tubular and interstitial cells in the obstructed kidney (13.17 ± 8.73 vs 3.00 ± 4.53 cells per high power field; P = 0.049 and 6.33 ± 3.27 vs 2.00 ± 2.35 cells per high power field; P = 0.036 vs sham-operated rats, 10 days after ligation). In rats with unilateral obstructive nephropathy, neither cilazapril nor losartan had an effect on tubular cell apoptosis. However, cilazapril caused a significant increase in the number of renal apoptotic interstitial cells (7.00 ± 9.74 vs 0.8 ± 1.41 cells per high power field, P = 0.019). Caspase-3 activity was not significantly different in rats with unilateral obstructive nephropathy than in sham-operated rats.

Conclusion

Rats with unilateral obstructive nephropathy had increased apoptosis of tubular and interstitial cells in comparison with sham-operated rats. Neither cilazapril nor losartan had an effect on tubular cell apoptosis, and cilazapril even increased interstitial cell apoptosis.Unilateral ureteral obstruction is a procedure that leads to a number of pathophysiological and morphological changes, including tubular atrophy, interstitial inflammation and fibrosis, and apoptosis of renal tubular and interstitial cells (1), which results in chronic obstructive nephropathy (2). Although apoptosis of renal tubule and interstitial cells is a prominent feature of unilateral obstructive nephropathy, the mechanisms involved in it have not been fully elucidated (3). Recent research has indicated that in unilateral obstructive nephropathy there is an association between the renin-angiotensin system and apoptotic alterations in the kidney (4).All the components of the renin-angiotensin system are present within the kidney (5), where both classic and alternate pathways are operational. The biological effect of angiotensin II is mediated by cell surface receptors, which can be divided into two main pharmacological classes, angiotensin II receptor subtypes I (AT1) (6) and angiotensin II receptor subtypes II (AT2) (7). The AT1 receptors are responsible for the major actions of angiotensin II, whereas the role of AT2 receptors is still not completely known (8,9). Angiotensin II may induce renal cell apoptosis by promoting oxidative stress, by causing vasoconstriction, and by enhancing the expression of adhesion molecules inducing chemotaxis and cytokine synthesis. In obstructive nephropathy, angiotensin II increases the expression of various factors, including transforming growth factor β1, tumor necrosis factor α (10), platelet derived growth factor, insulin-like growth factor, osteopontin, vascular cell adhesion molecule-1, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and nuclear factor kappa-B (3).The process of apoptosis is a complex mechanism in which a major role is played by caspases (cysteinyl aspartate-specific proteinase) (11). Many apoptosis-inducing factors (12) transport the signals through the cytoplasm via mediating molecules. These signals are transduced through cytosol by an ever-increasing number of mediator molecules that belong to distinct families (13), each of which mediates a specific apoptotic pathway (14). These pathways, however, converge into a common arm, characterized by an orderly activation of caspases (15), which serve as effector molecules for apoptosis (16,17). One of the best studied effector caspases is caspase-3, the central molecule at the crossroad of all known apoptotic pathways (18).Although the role of angiotensin II in the pathophysiology of unilateral obstructive nephropathy is clear, there is a shortage of studies comparing the effects of angiotensin-converting enzyme (ACE) inhibition and AT1 antagonism on renal tubule and interstitial cell apoptosis. We hypothesized that both ACE inhibitor (cilazapril) and AT1 receptor antagonist (losartan) would decrease renal tubular and interstitial apoptosis. Also, we expected that cilazapril would have greater antiapoptotic effect than losartan, because of the well-known association between ACE inhibition and increased nitric oxide (NO) generation (9). The potential pharmacologic difference between the two classes of anti-angiotensin drugs with different effects on renal cell apoptosis may have clinical therapeutic implications for patients with obstructive nephropathy.     

Use of concentrated bone marrow aspirate and platelet rich plasma during minimally invasive decompression of the femoral head in the treatment of osteonecrosis

The aim of this paper is to describe our surgical procedure for the treatment of osteonecrosis of the femoral head using a minimally invasive technique. We have limited the use of this procedure for patients with pre-collapse osteonecrosis of the femoral head (Ficat Stage I or II). To treat osteonecrosis of the femoral head at our institution we currently use a combination of outpatient, minimally invasive iliac crest bone marrow aspirations and blood draw combined with decompressions of the femoral head. Following the decompression of the femoral head, adult mesenchymal stem cells obtained from the iliac crest and platelet rich plasma are injected into the area of osteonecrosis. Patients are then discharged from the hospital using crutches to assist with ambulation. This novel technique was utilized on 77 hips. Sixteen hips (21%) progressed to further stages of osteonecrosis, ultimately requiring total hip replacement. Significant pain relief was reported in 86% of patients (n = 60), while the rest of patients reported little or no pain relief. There were no significant complications in any patient. We found that the use of a minimally invasive decompression augmented with concentrated bone marrow and platelet rich plasma resulted in significant pain relief and halted the progression of disease in a majority of patients.Osteonecrosis of the femoral head (ONFH) occurs when the cells of the trabecular bone and marrow in the femoral head spontaneously die, leading to fracture and collapse of the articular surface (1,2). In the US, every year ONFH occurs in 10 000-20 000 adults between the ages of 20 and 60 (1,3,4). Once collapse occurs, severe pain ensues, and the disease course rarely regresses (5-8). In order to halt disease progression and provide pain relief, 80% of patients suffering from ONFH will require a total hip arthroplasty (THA); typically at a younger age than patients undergoing a THA for osteoarthritis (9-11).Although ONFH is a common indication for THA, the etiology of the disease is still unknown (12,13). ONFH is thought to be a multifactorial disease, with patients reporting a history of exposure to one or more risk factors, including trauma to the hip, alcohol abuse, corticosteroid use, hemoglobinopathies, pregnancy, coagulopathies, organ transplant, chemotherapy, Caisson disease, HIV, and autoimmune conditions; however in some patients the risk factor remains unknown, and the disease is termed “idiopathic” ONFH (12-16). Recent studies looking at the gentics risks of ONFH have resulted in identifying an autosomal dominant mutation in collagen type II gene (COL2 A1 gene) (17); which has been associated with genetic polymorphisms in alcohol metabolizing enzymes and the drug transport proteins (18,19).If the disease course is recognized before collapse of the subchondral bone and cartilage, patients can be treated with core decompression of the femoral head including Ficat Stage I or II (12,20,21). This technique has been used for over four decades, however randomized control trials have failed to show that this procedure alone halts disease progression and collapse (4). Recently, concentrated bone marrow autograft has been used to augment the decompression site to attempt to repopulate the femoral head with human mesenchymal stem cells (hMSC) (13,22,23). This aim of this paper is to describe our surgical technique and early clinical results using autologous bone marrow concentrate with platelet rich plasma and a minimally invasive decompression for the treatment of ONFH.     

Pharmacotherapy of treatment-resistant combat-related posttraumatic stress disorder with psychotic features

Aim

To assess retrospectively the clinical effects of typical (fluphenazine) or atypical (olanzapine, risperidone, quetiapine) antipsychotics in three open clinical trials in male Croatian war veterans with chronic combat-related posttraumatic stress disorder (PTSD) with psychotic features, resistant to previous antidepressant treatment.

Methods

Inpatients with combat-related PTSD were treated for 6 weeks with fluphenazine (n = 27), olanzapine (n = 28) risperidone (n = 26), or quetiapine (n = 53), as a monotherapy. Treatment response was assessed by the reduction in total and subscales scores in the clinical scales measuring PTSD (PTSD interview and Clinician-administered PTSD Scale) and psychotic symptoms (Positive and Negative Syndrome Scale).

Results

After 6 weeks of treatment, monotherapy with fluphenazine, olanzapine, risperidone, or quetiapine in patients with PTSD significantly decreased the scores listed in trauma reexperiencing, avoidance, and hyperarousal subscales in the clinical scales measuring PTSD, and total and subscales scores listed in positive, negative, general psychopathology, and supplementary items of the Positive and negative syndrome scale subscales, respectively (P<0.001).

Conclusion

PTSD and psychotic symptoms were significantly reduced after monotherapy with typical or atypical antipsychotics. As psychotic symptoms commonly occur in combat-related PTSD, the use of antipsychotic medication seems to offer another approach to treat a psychotic subtype of combat-related PTSD resistant to previous antidepressant treatment.In a world in which terrorism and conflicts are constant threats, and these threats are becoming global, posttraumatic stress disorder (PTSD) is a serious and global illness. According to the criteria from the 4th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1), exposure to a life-threatening or horrifying event, such as combat trauma, rape, sexual molestation, abuse, child maltreatment, natural disasters, motor vehicle accidents, violent crimes, hostage situations, or terrorism, can lead to the development of PTSD (1,2). The disorder may also be precipitated if a person experienced, saw, or learned of an event or events that involved actual or threatened death, serious injury, or violation of the body of self or others (3,4). In such an event, a person’s response can involve intense fear, helplessness, or horror (3,4). However, not all persons who are exposed to a traumatic event will develop PTSD. Although the stress reaction is a normal response to an abnormal situation, some extremely stressful situations will in some individuals overwhelm their ability to cope with stress (5).PTSD is a chronic psychiatric illness. The essential features of PTSD are the development of three characteristic symptom clusters in the aftermath of a traumatic event: re-experiencing the trauma, avoidance and numbing, and hyperarousal (1,6). The core PTSD symptoms in the re-experiencing cluster are intrusive memories, images, or perceptions; recurring nightmares; intrusive daydreams or flashbacks; exaggerated emotional and physical reactions; and dissociative experiences (1,6,7). These symptoms intensify or re-occur upon exposure to reminders of the trauma, and various visual, auditory, or olfactory cues might trigger traumatic memories (3,4). The avoidance and numbing cluster of symptoms includes efforts to avoid thoughts, feelings, activities, or situations associated with the trauma; feelings of detachment or alienation; inability to have loving feelings; restricted range of affect; loss of interest; and avoidance of activity. The hyperarousal cluster includes exaggerated startle response, hyper-vigilance, insomnia and other sleep disturbances, difficulties in concentrating, and irritability or outbursts of anger. PTSD criteria include functional impairment, which can be seen in occupational instability, marital problems, discord with family and friends, and difficulties in parenting (3,4,8). In addition to this social and occupational dysfunction, PTSD is often accompanied by substance abuse (9) and by various comorbid diagnoses, such as major depression (10), other anxiety disorders, somatization, personality disorders, dissociative disorders (7,11), and frequently with suicidal behavior (12). Combat exposure can precipitate a more severe clinical picture of PTSD, which may be complicated with psychotic features and resistance to treatment. War veterans with PTSD have a high risk of suicide, and military experience, guilt about combat actions, survivor guilt, depression, anxiety, and severe PTSD are significantly associated with suicide attempts (12).The pharmacotherapy treatment of PTSD includes the use of antidepressants, such as selective serotonin reuptake inhibitors (fluvoxamine, fluoxetine, sertraline, or paroxetine) as a first choice of treatment, tricyclic antidepressants (desipramine, amitriptyline, imipramine), monoamine oxidase inhibitors (phenelzine, brofaromine), buspirone, and other antianxiety agents, benzodiazepines (alprazolam), and mood stabilizers (lithium) (13-16). Although the pharmacotherapy of PTSD starts with antidepressants, in treatment-refractory patients a new pharmacological approach is required to obtain a response. In treatment-resistant patients, pharmacotherapy strategies reported to be effective include anticonvulsants, such as carbamazepine, gabapentine, topiramate, tiagabine, divalproex, lamotrigine (14,17); anti-adrenergic agents, such as clonidine (although presynaptic α2-adrenoceptor agonist, clonidine blocks central noradrenergic outflow from the locus ceruleus), propranolol, and prazosin (13,14), opiate antagonists (13), and neuroleptics and antipsychotics (14,17,18).Combat exposure frequently induces PTSD, and combat-related PTSD might progress to a severe form of PTSD, which is often refractory to treatment (19-21). Combat-related PTSD is frequently associated with comorbid psychotic features (11,14,17,19-21), while psychotic features add to the severity of symptoms in combat-related PTSD patients (19,22-24). These cases of a more severe subtype of PTSD, complicated with psychotic symptoms, require the use of neuroleptics or atypical antipsychotic drugs (14,17,25-27).After the war in Croatia (1991-1995), an estimated million people were exposed to war trauma and about 10 000 of the Homeland War veterans (15% prevalence) have developed PTSD, with an alarmingly high suicide rate (28). The war in Croatia brought tremendous suffering, not only to combat-exposed veterans and prisoners of war (29), but also to different groups of traumatized civilians in the combat zones, displaced persons and refugees, victims of terrorist attacks, civilian relatives of traumatized war veterans and terrorist attacks victims, and traumatized children and adolescents (30). Among Croatian war veterans with combat-related PTSD, 57-62% of combat soldiers with PTSD met criteria for comorbid diagnoses (8-11), such as alcohol abuse, major depressive disorder, anxiety disorders, panic disorder and phobia, psychosomatic disorder, psychotic disorders, drug abuse, and dementia. In addition to different comorbid psychiatric disorders, a great proportion of war veterans with combat-related PTSD developed psychotic features (8,11,25,26), which consisted of psychotic depressive and schizophrenia-like symptoms (suggesting prominent symptoms of thought disturbances and psychosis). Psychotic symptoms were accompanied by auditory or visual hallucinations and delusional thinking in over two-thirds of patients (25,26). Delusional paranoid symptoms occurred in 32% of patients (25,26). The hallucinations were not associated exclusively with the traumatic experience, while the delusions were generally paranoid or persecutory in nature (25,26). Although psychotic PTSD and schizophrenia share some similar symptoms, there are clear differences between these two entities, since PTSD patients still retain some insight into reality and usually do not have complete disturbances of affect (eg, constricted or inappropriate) or thought disorder (eg, loose associations or disorganized responses).This proportion of veterans with combat-related PTSD refractory to treatment (18-20) and with co-occurring psychotic symptoms requires additional pharmacological strategies, such as the use of neuroleptics (25) or atypical antipsychotics (14,17,26). Studies evaluating the use of antipsychotics in combat-related PTSD with psychotic features are scarce, and antipsychotics were frequently added to existing medication in the treatment of PTSD.In this study, we compared retrospectively the clinical effects of four antipsychotic drugs – a neuroleptic drug (fluphenazine) and three atypical antipsychotics (olanzapine, risperidone and quetiapine) – in treatment-resistant male war veterans with combat-related PTSD with psychotic features.     

Predictive value of dental readiness and psychological dimensions for oral health-related quality of life in Croatian soldiers: a cross-sectional study

Aim

To determine the predictive value of dental readiness and psychological dimensions for oral health-related quality of life (OHRQoL) in Croatian soldiers.

Methods

The sample consisted of 402 consecutive soldiers aged 21 to 54 years classified into the following groups according to dental readiness: Class 1 – not requiring dental treatment (N = 54), Class 2 – unlikely to need emergency treatment within 12 months (N = 205), and Class 3 – very likely to need treatment within 12 months (N = 143). OHRQoL was assessed by the Oral Health Impact Profile and psychological dimensions by the Brief Symptom Inventory and Dental Anxiety Scale.

Results

Multivariate analysis showed that Class 3 soldiers had higher frequency of psychological discomfort, psychological disability, and physical pain and handicap than Class 1 soldiers (P = 0.019). Multiple linear regression showed that longer military experience, higher level of dental anxiety, and dental unreadiness were significant predictors of lower OHRQoL (P < 0.050) but accounted for low variability. None of the single psychological symptomatic dimensions was a significant predictor of OHRQoL.

Conclusion

Although this study found a moderate association between OHRQoL and clinical, military, demographic, and psychological variables, the significant predictors could be used as a basis for further research of clinical and psychosocial factors of OHRQoL.General and oral health have multiple effects on the quality of life (QoL), which can be decreased by pain, discomfort, and difficulties in everyday physical activities, chewing, speech, hygiene, relaxation, and social contact (1-3). Oral health is an often neglected dimension of health, especially among soldiers, although it affects their QoL and combat readiness (4). An inadequately assessed combat readiness may reduce the effectiveness of the military unit and cause human risks and financial expenses due to transportation of soldiers to health facilities (5). Acute dental conditions may cause losses of over 18 000 man-days per division per year (6,7). Dental non-battle injury emergency rates averaged 16% during Vietnam War (8), and in US military units in peacekeeping missions in Bosnia and Herzegovina the rate of emergency dental conditions was 156-170 per 1000 soldiers per year (9).Psychological personality dimensions might influence self-perceived QoL, thus potentially affecting the reported health impairment and combat disability. We hypothesized that the psychological dimensions that may affect the self-perception of OHRQoL were somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideas, psychoticism, and dental anxiety.The studies of HRQoL in soldiers have so far been sporadic (10,11). There were studies that assessed the impact of oral health on combat readiness or the consequences of wartime events on oral health, but often overlooked the QoL assessment (6,12-14). To the best of our knowledge, no studies so far have assessed the effect of psychological dimensions on the self-perceived OHRQoL.The aim of the research was to explore the predictive value of dental readiness and psychological dimensions for OHRQoL. The hypothesis was that OHRQoL was a specific dimension of combat readiness that was significantly correlated with clinically assessed dental readiness and psychological symptomatic dimensions.     

Anterior instrumentation for correction of adolescent thoracic idiopathic scoliosis: historic prospective study

Aim

To compare the results of anterior instrumentation and standard posterior procedure for correction of adolescent thoracic idiopathic scoliosis.

Methods

The study included 50 patients with adolescent thoracic idiopathic scoliosis who underwent corrective spinal surgery. Anterior spinal fusion by use of modified Zielke ventral derotation system (anterior approach to spine through thorax) was performed in 25 patients, whereas posterior approach was used in 25 patients. The average preoperative thoracic curve in coronal plane was 66.7 ± 9.9° and 65.0 ± 11.7° in the anterior and posterior correction groups, respectively. The median age of patients before surgery was 14 years (range, 12-18) in the anterior and 16 years (range, 13-18) in the posterior correction group. Women-to-men ratio was 22 to 3 in each group. Coronal and sagittal correction, apical vertebral body rotation, rib hump, and rib depression correction were measured before surgery and at the first (30 days after surgery) and at the second follow-up visit (at least 2 years after surgery). Posteroanterior and laterolateral radiographs of the erect spine were used (according to the method of Cobb and Nash-Moe) to assess coronal, sagittal, and horizontal plane corrections. Rib hump and rib depression were measured with Thulbourne-Gillespie measuring device. The differences in scoliosis correction parameters in the two groups were tested with Student two-tailed t test.

Results

In the coronal plane, the thoracic curve of 66.7 ± 9.9° before surgery in the anterior correction group was reduced to 14.8 ± 8.7° after surgery (78.1 ± 12.4% relative correction), and the curve of 65.0 ± 11.7° in the posterior correction group was corrected to 29.2 ± 7.8° after surgery (55.1 ± 8.6% relative correction) (P<0.001). Apical vertebral body rotation correction according to the Nash-Moe classification from 2.0 ± 0.4° to 0.8 ± 0.6° was achieved in the anterior correction group (62.0 ± 26.6% relative correction) and from 1.7 ± 0.5° to 1.4 ± 0.5° in the posterior correction group (12.0 ± 21.8% relative correction) (P<0.001). Rib hump correction from 22.4 ± 15.5 mm to 5.4 ± 5.2 mm was found in the anterior correction group (70.9 ± 26.0% relative correction) and from 25.3 ± 7.0 mm to 13.6 ± 6.8 mm (48.4 ± 16.5% relative correction) in the posterior correction group (P = 0.084).

Conclusion

Compared with the standard posterior approach, the anterior approach resulted in better three-dimensional correction of idiopathic thoracic scoliosis.In patients with adolescent idiopathic scoliosis, the spine is curved to the side and rotated around the long axis, producing unilateral prominence of the trunk. The prominence of the rib cage is visible on the convex side of the curve and depression is present on the concave side. It is often the rib hump rather than the lateral curve that is the major cosmetic deformity (1). The prevalence of idiopathic scoliosis varies significantly because of the lack of uniformity in defining target population and the use of different definitions of scoliosis (2,3).Traditionally, thoracic idiopathic scoliosis has been treated by posterior instrumentation and fusion, which is still the gold standard (4). Harrington instrumentation was the first accepted implant used for the correction of scoliosis (5). The next major step in scoliosis surgery was the use of Luque rods with sublaminar wires (6). Posterior spinal fusion with multisegmented hook-rod systems was widely used in the mid to late 1980s, with successful results (7). Suk et al (8) reported extensively on the posterior use of pedicle screw fixation for thoracic scoliosis, which also produced excellent results. Anterior spinal fusion with Dwyer instrumentation represented the first generation of anterior implants for correction of lumbar scoliosis (9). Subsequent to that, Zielke rigid rod anterior instrumentation has been adapted and used to save fusion levels in the distal lumbar spine (10). Because of the problems with a high rate of rod breakage reported during the follow-up study of Zielke instrumentation (11) used anteriorly for thoracic, thoracolumbar, and lumbar curves, a new rod-screw-nut system was developed. Slot added another rod to Zielke’s instrumentation to correct kyphosis (12). The Harms Study Group elaborated and refined the concepts of anterior instrumentation for thoracic idiopathic scoliosis (13).The posterior approach has a long history of success with different instrumentations, allowing a solution for any combination of thoracic deformities, whereas the anterior approach offers no possibility of correction for partial or complete structural left high thoracic curve (4). However, correction of the rotational component of thoracic spine deformity is not affected significantly with posterior approach (14,15). Kovač et al (16) showed better thoracic volume correction after the anterior than after the posterior approach. In some cases, a significant number of distal vertebral segments can be saved by use of anterior instrumentation, with an excellent spontaneous lumbar curve correction (17).Controversy still exists about the benefits of the anterior in comparison with the posterior approach (4). The aim of this study was to compare the scoliosis correction after the anterior instrumentation with that obtained by the standard posterior procedure in patients with adolescent thoracic idiopathic scoliosis.     

The prevalence of domestic violence in primary care patients in Slovenia in a five-year period (2005-2009)

Aim

To estimate the prevalence of exposure to domestic violence in primary care patients in Slovenia and determine the associated factors.

Methods

In a systematic cross-sectional survey, 70 physicians from 70 family medicine practices from urban and rural settings conducted interviews with every fifth patient from January 15 to February 15, 2010.

Results

Of 2075 patients (98.8% response rate), 372 (17.9%) were exposed to psychological or physical violence in the family in the last five years. Factors that increased the chances of exposure to psychological and physical violence were female sex (odds ratio [OR], 3.27; 95% confidence interval [CI], 2.24-4.76; P < 0.001; OR, 4.52; 95% CI, 2.83-7.20; P < 0.001, respectively) and formal divorce (OR, 2.08; 95% CI, 1.35-3.21; P = 0.001; OR, 2.72; 95% CI, 1.73-4.29; P < 0.001, respectively). Factors that decreased the chances of exposure to psychological violence were age of 65 years or above (OR, 0.56; 95% CI, 0.33-0.96, P = 0.035) and single status (OR, 0.43; 95% CI 0.21-0.86, P = 0.016), while age of 65 years or above (OR, 0.43; 95% CI, 0.23-0.79, P = 0.007) and parenting of two children (OR, 0.51; 95% CI, 0.29-0.90, P = 0.020) decreased the chances of exposure to physical violence.

Conclusions

We found the rate of exposure to psychological and physical violence of 17.9%, which indicates that this problem is a serious public health issue that needs to be addressed by adequate measures. The identified risk and protective factors could serve as a valid guidance for family physicians dealing with physical violence.Domestic violence is a serious health issue, with consequences ranging from physical impairments to psychological symptoms, physical trauma, and death (1-3). Its prevalence is between 5% and 30% (4-6), and about 90% of the perpetrators are family members (1). The exposure to violence inevitably leads to more frequent use of health services, while unrecognized causes of health problems in victims of violence can lead to unnecessary consultations, unwarranted diagnostic procedures, and ineffective health care (5-10). Health services often miss the opportunity to prevent violence (11), probably because victims hesitate to disclose it and medical health providers hesitate to ask about it, even if a number of guidelines and recommendations has been published (12-17). A meta-analysis (18) has showed that 63% of female patients in primary health care would approve of screening on domestic violence, and the percentage is even higher among those who have experienced violence (18). However, despite the recommendations of professional organizations, only 10% of physicians actively ask their patients about violence (19). The aim of the study was to estimate the prevalence of domestic violence in family care settings in Slovenia and to identify the factors influencing it.