Patterns of internet use and mental health of high school students in Istria County,Croatia: cross-sectional study

Aim

To examine associations between different forms of internet use and a number of psychological variables related to mental health in adolescents.

Methods

A cross-sectional survey was carried out on a representative sample of students (N = 1539) from all high schools in the region of Istria in Croatia (14-19 years). The associations between four factors of internet use and nine mental health indicators were analyzed using canonical correlation analysis.

Results

The four canonical functions suggested a significant association between different types of internet use and specific indicators of mental health (P < 0.001). Problematic internet use, more typical among boys, was associated with general aggressive behavior and substance abuse (P < 0.001). Experiences of harassment, more typical among girls, were associated with health complaints, symptoms of depression, loneliness, and fear of negative evaluation (P < 0.001). Using the internet for communication and entertainment was associated with better relationships with peers (P < 0.001), while use of the internet for academic purposes was associated with conscientiousness (P < 0.001).

Conclusion

The results suggest that different patterns of internet use are significantly associated with specific sets of positive and negative mental health indicators. The data support the assumption that internet use can have both positive and adverse effects on the mental health of youth.New technologies, and especially the use of computers and the internet, are part of the everyday lives of young people and have a significant impact on their psychological development. Indeed, this mass use of new media technologies presents parents and society with a challenge to protect and support the positive development of children and youth. To date, a number of studies have examined the positive and negative aspects of using internet technologies.Literature points to several positive aspects of internet use (1,2): for information acquiring, communication, and social networking, entertainment, and online shopping. More specifically, adolescents use the internet as a useful source of information about school assignments, daily events, interests and hobbies, or health and sexuality concerns. In these instances, online activities aimed at connecting with peers have a significant place. Visiting social networking sites and using communication tools such as email, chat, forums, and discussion groups enables the creation of friendships and social groups and contributes to the development of personal identity (3). The use of computers and the internet (cyberspace) has also been argued to provide opportunities for new and faster learning, exercising one''s self-control, considering different opinions, expressing one''s attitudes and tolerance, and developing skills in critical thinking and decision-making (4). Best et al (5) found that use of online communication technologies contributed to increased self-confidence, better perception of social support, greater social capital, positive experimenting with one’s own identity, and greater opportunities for open self-disclosure. Conversely, adolescents who do not use the internet might trail behind in the development of such positive attitudes and traits and risk being rejected by their peers (6). Finally, Livingstone et al (7) found that a certain amount of risk exposure was useful in building resilience.In contrast to these positive influences of internet use, harmful effects of internet abuse range from exposure to inappropriate sexual content, pornography, and violence (2,7) to humiliation and cyber-bullying (6,8-10) and internet addiction (11,12). Research has confirmed the link between internet abuse and social isolation, depression and, anxiety (1,5,13,14), alcohol and drug abuse and gambling (15), and problems with physical health (16). Ybarra and Mitchell (17) found a connection between experiences of threats or humiliation in the virtual world and absences from school, lower school achievement, substance use disorders, delinquency and depression. Fekkes et al (18) point to the association between victimizing experiences and a number of physical, emotional, and behavioral problems, such as headaches, tension, fatigue, loss of appetite, enuresis, and sleeping problems. Slonje and Smith (19) define such experiences as a product of cyber-bullying and argue that this can be viewed as another form of aggressive behavior. Gender has emerged as a significant predictor of the manner in which the internet is used. Specifically, girls tend to experience victimizing experiences, while boys more frequently demonstrate antisocial behavior (20,21).Although many studies have identified both positive and negative correlates of internet use, there have been only a few studies using complex multivariate analyses to identify broader patterns of internet use and adolescent mental health (22,23). Less is known about how adolescents exhibiting different personalities and different emotional and behavioral patterns engage in internet use and what might be the consequences of this engagement. The aim of this study was to determine the specific patterns of internet use and mental health among adolescents. The following hypotheses were tested:H1: Problematic internet use is associated with externalized symptoms and other negative indicators of mental health. Exposure to victimizing and disturbing content on the internet is associated with internalized symptoms and negative indicators of mental health.H2: Prosocial internet use (aimed at connecting with peers and entertainment) and internet use for school purposes are associated with positive aspects of mental health.H3: Problematic internet use is present more often in young men, while exposure to disturbing content on the internet is more frequently experienced by young women.     

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.     

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.     

Patients with Combat-related and War-related Posttraumatic Stress Disorder 10 Years After Diagnosis

Aim

To establish how many patients diagnosed with posttraumatic stress disorder (PTSD) in 1996 used psychiatric facilities and had psychiatric symptoms 10 years later, and assess their sociodemographic characteristics, comorbid disorders, and type of treatment.

Methods

Medical records of patients diagnosed with PTSD in 1996 were reviewed in the period 2007-2009 and the patients who contacted a psychiatrist in that period (n = 85) and those who did not (n = 158) were compared.

Results

There were 36.7% of men and 20% of women diagnosed with PTSD in 1996 who contacted a psychiatrist in the period 2007-2009. Patients who contacted a psychiatrist and those who did not did not differ in sex, age, the number of visits and hospitalizations in 1996, and employment status. The majority of patients still had PTSD and/or were enduring personality change in the period 2007-2009, and 54.8% had some comorbidity (mostly depression, alcohol-related disorders, and personality disorders). Patients were most often treated with anxiolytics and antidepressants.

Conclusion

Ten years after the traumatic experience, one third of patients with PTSD received psychiatric help, regardless of their sex, age, and employment status. Half of them had comorbid disorders and the majority of them were treated with anxiolytics and antidepressants.Posttraumatic stress disorder (PTSD) is a mental disorder that develops in 9-25% of war veterans (1-4), mainly in the first two years after the traumatic experience (5,6), but sometimes can develop years later (7,8). A similar prevalence was also found among Croatian war veterans (5-9). In the majority of cases (80-98%), PTSD is comorbid with other mental disorders: alcohol abuse, depression, anxiety disorders, and somatization (5,9-11).PTSD can also develop after a war-related trauma that is not necessarily combat-related, and the lifetime prevalence of PTSD in this population is 15-38% (12) and the prevalence of anxiety and depressive disorders is even higher (13,14).Many patients in Croatia had symptoms of PTSD and used health facilities for treatment years after the war (5-9). In the former Yugoslavia, 84% of untreated war-related PTSD patients still had PTSD symptoms years after the war (15). Resolution of PTSD is observed in 50-60% of cases (4,16).Combat-related PTSD causes more functional impairment and is less responsive to treatment than PTSD related to other traumas (17-19). It is unclear whether this happens because there is indeed a difference between the two types of PTSD or some of the patients aggravate their symptoms in order to get compensation (17,18,20). Some studies show that the use of health facilities decreases after obtaining war veteran status and compensation, but others show that the patients who had obtained the status and compensation used medical facilities more often than those who had not (20-23).The aim of this study was to establish how many patients diagnosed with PTSD in 1996 used psychiatric facilities and had psychiatric symptoms 10 years later and assess their comorbidities, sociodemographic characteristics, and type of 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.     

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.     

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.     

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.     

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.     

Sex-specific chronic stress response at the level of adrenal gland modifies sexual hormone and leptin receptors

Aim

To compare cardiometabolic risk-related biochemical markers and sexual hormone and leptin receptors in the adrenal gland of rat males, non-ovariectomized females (NON-OVX), and ovariectomized females (OVX) under chronic stress.

Methods

Forty six 16-week-old Sprague-Dawley rats were divided into male, NON-OVX, and OVX group and exposed to chronic stress or kept as controls. Weight, glucose tolerance test (GTT), serum concentration of glucose, and cholesterol were measured. Adrenal glands were collected at the age of 28 weeks and immunohistochemical staining against estrogen beta (ERβ), progesterone (PR), testosterone (AR), and leptin (Ob-R) receptors was performed.

Results

Body weight, GTT, serum cholesterol, and glucose changed in response to stress as expected and validated the applied stress protocol. Stressed males had significantly higher number of ERβ receptors in comparison to control group (P = 0.028). Stressed NON-OVX group had significantly decreased AR in comparison to control group (P = 0.007). The levels of PR did not change in any consistent pattern. The levels of Ob-R increased upon stress in all groups, but the significant difference was reached only in the case of stressed OVX group compared to control (P = 0.033).

Conclusion

Chronic stress response was sex specific. OVX females had similar biochemical parameters as males. Changes upon chronic stress in adrenal gland were related to a decrease in testosterone receptor in females and increase in estrogen receptor in males.Maintaining homeostasis is often challenged by different types of stressors (1). Homeostasis is regulated by a complex endocrine processes engaging the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic autonomic system (2-4). Stress can occur either in acute or chronic form with different consequences – the acute stress mostly induces the ˝fight or flight˝ response, while chronic stress promotes long term changes, which can lead to a variety of diseases (5,6). If stress is of sufficient magnitude and duration, the action of HPA is unsuppressed and results in prolonged elevation of cortisol (7), induced production of energy, vasoconstriction, lipolysis, proteolysis, immunosuppression, and suppression of reproductive function to save energy and retain overall homeostasis (8). Women are generally less susceptible to chronic stress up to the period of menopause, when the loss of protective hormones, estrogen and progesterone, occurs and thus they become prone to development of depression, anxiety, or schizophrenia (9). In contrast, men are generally more susceptible and sensitive to chronic stress, showing changes in feeding habits and decreased body weight (10,11).Chronic stress can cause the development of cardiovascular disorder, obesity, and diabetes, which can be reflected in serum cholesterol, glucose, and decreased glucose tolerance (12-14). There is a strong correlation between stress and sexual hormones, but the mechanisms by which estrogen, testosterone, and progesterone exert their possible protective role under stress conditions are not fully explored. Sexual hormones affect stress outcome and stress hormones affect the levels of sexual hormones (15-17). Testosterone is activated during stress response in rats and humans (18,19) and tends to increase more in men than women (20). Estrogen lowers the stress-induced response in women and men (9,21). Estrogens and progesterone are produced even after ovariectomy by adrenal glands (22) but it is not known if such compensation can withstand additional challenge like stress. Another possible player in stress response is leptin (Ob), hormone responsible for maintaining body weight, which is synthesized and secreted by adipose tissue (23), exerting its effects through the leptin receptor (Ob-R) (24). Chronic stress models imply a direct link between stress response and leptin (25,26). Receptors for leptin are present in the adrenal gland (27). The aim of this study was to investigate cardiovascular risk parameters and changes in leptin and sexual hormone receptors in adrenal gland during chronic stress. There is a clinically relevant change in the onset of cardiometabolic risk between healthy women and women with premature ovarian failure (28) and because of that ovariectomized female rats were included in the study.     

Attitudes of Slovenian family practice patients toward changing unhealthy lifestyle and the role of family physicians: cross-sectional study

Aim

To assess patients’ attitudes toward changing unhealthy lifestyle, confidence in the success, and desired involvement of their family physicians in facilitating this change.

Methods

We conducted a cross-sectional study in 15 family physicians’ practices on a consecutive sample of 472 patients (44.9% men, mean age  [± standard deviation] 49.3 ± 10.9 years) from October 2007 to May 2008. Patients were given a self-administered questionnaire on attitudes toward changing unhealthy diet, increasing physical activity, and reducing body weight. It also included questions on confidence in the success, planning lifestyle changes, and advice from family physicians.

Results

Nearly 20% of patients planned to change their eating habits, increase physical activity, and reach normal body weight. Approximately 30% of patients (more men than women) said that they wanted to receive advice on this issue from their family physicians. Younger patients and patients with higher education were more confident that they could improve their lifestyle. Patients who planned to change their lifestyle and were more confident in the success wanted to receive advice from their family physicians.

Conclusion

Family physicians should regularly ask the patients about the intention of changing their lifestyle and offer them help in carrying out this intention.Unhealthy lifestyle, including unhealthy diet and physical inactivity, is still a considerable health problem all over the world. Despite publicly available evidence about the health risks of unhealthy lifestyle, people still find it hard to improve their unhealthy diet and increase physical activity. Previous studies have shown that attitudes toward lifestyle change depended on previous health behavior, awareness of unhealthy lifestyle, demographic characteristics, personality traits, social support, family functioning, ongoing contact with health care providers, and an individual’s social ecology or network (1-4).As community-based health education approaches have had a limited effect on health risk factors reduction (3,5), the readiness-to-change approach, based on two-way communication, has become increasingly used with patients who lead an unhealthy lifestyle (3,6,7). Family physicians are in a unique position to adopt this approach, since almost every patient visits his/hers family physician at least once in five years (8). Previous studies showed that patients highly appreciated their family physicians’ advice on lifestyle changes (9,10). Moreover, patients who received such advice were also more willing to change their unhealthy habits (3,7,11). The reason for this is probably that behavioral changes are made according to the patient’s stage of the motivational circle at the moment of consultation (12), which can be determined only by individual approach.Although family physicians are convinced that it is their task to give advice on health promotion and disease prevention, in practice they are less likely to do so (13). The factors that prevent them from giving advice are time (14,15), cost, availability, practice capacity (14), lack of knowledge and guidelines, poor counseling skills (16), and personal attitudes (17). It also seems that physicians’ assessment varies considerably according to the risk factor in question. For example, information on diet and physical activity are often inferred from patients’ appearance rather than from clinical measurements (14). Also, health care professionals seldom give advice on recommended aspects of intervention that could facilitate behavioral change (18). As a large proportion of primary care patients are ready to lose weight, improve diet, and increase exercise (19), it is even more important that their family physicians provide timely advice.So far, several studies have addressed patients’ willingness to make lifestyle change (2-5,20) and the provision of professional advice (3,5,7,10,11). However, none of these studies have investigated the relation between these factors. So, the aim of our study was to assess the relation between patients’ attitudes toward changing unhealthy lifestyle, confidence in success, and the desired involvement of their family physicians in facilitating the change.     

Impact of ovariectomy,high fat diet,and lifestyle modifications on oxidative/antioxidative status in the rat liver

Aim

To estimate the impact of high fat diet and estrogen deficiency on the oxidative and antioxidative status in the liver of the ovariectomized rats, as well as the ameliorating effect of physical activity or consumption of functional food containing bioactive compounds with antioxidative properties on oxidative damage in the rat liver.

Methods

The study was conducted from November 2012 to April 2013. Liver oxidative damage was determined by lipid peroxidation levels expressed in terms of thiobarbituric acid reactive substances (TBARS), while liver antioxidative status was determined by catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) activities, and glutathione (GSH) content. Sixty-four female Wistar rats were divided into eight groups: sham operated and ovariectomized rats that received either standard diet, high fat diet, or high fat diet supplemented with cereal selenized onion biscuits or high fat diet together with introduction of physical exercise of animals.

Results

High fat diet significantly increased TBARS content in the liver compared to standard diet (P = 0.032, P = 0.030). Furthermore, high fat diet decreased the activities of CAT, GR, and GST, as well as the content of GSH (P < 0.050). GPx activity remained unchanged in all groups. Physical activity and consumption of cereal selenized onion biscuits showed protective effect through increased GR activity in sham operated rats (P = 0.026, P = 0.009), while in ovariectomized group CAT activity was increased (P = 0.018) in rats that received cereal selenized onion biscuits.

Conclusion

Feeding rats with high fat diet was accompanied by decreased antioxidative enzyme activities and increased lipid peroxidation. Bioactive compounds of cereal selenized onion biscuits showed potential to attenuate the adverse impact of high fat diet on antioxidative status.Reactive oxygen species (ROS) are common by-products of many oxidative biochemical and physiological processes, and are also involved in numerous physiological and pathophysiological processes. While in low concentrations they may be beneficial in processes such as intracellular signaling and defense against microorganisms, higher concentrations cause cell damage via oxidative modification of proteins, lipids, and DNA, and thus play a major role in the pathogenesis of a variety of human diseases (1). The balance between production and neutralization of ROS is maintained by antioxidant defense system. The system includes antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST), and a number of low mass non-enzymatic molecules that are scavenging ROS, such as glutathione (GSH) (2,3). An imbalance between ROS production and the cellular antioxidant defense system leads to oxidative stress, which results in lipid peroxidation (LPO) and increased tissue injury (4,5). In liver tissue, this process leads to fibrosis, chronic inflammation, and apoptosis (6).It has been postulated that oxidative processes and antioxidant defense can be sex-related (7). Such sex-related differences may be due to gonadotropic hormones, primarily estrogens (8). Estradiol and its derivatives are strong endogenous antioxidants that reduce LPO levels in the liver and serum (9,10). Also, estrogens can up-regulate the expression of antioxidative enzymes, such as GPx and SOD (10-12). There is evidence that imbalance in oxidative and antioxidative status is present in women during postmenopausal life (13). The lack of protective action of estrogens is known to cause serious metabolic disturbances, and oxidative stress is thought to be one of the suspected mechanisms (14). Ovariectomy in rats is a commonly used animal model for elucidating the impact of estrogen insufficiency and metabolic consequences (15,16). Estrogen insufficiency is often associated with increased food intake and body weight, therefore high fat diet (HFD)-induced obesity could be an additional problem in menopausal women, and it could affect the levels of oxidative stress in the liver.Feeding rats with HFD was proved to be a useful model of effects of dietary fat in humans (17). HFD is considered as a major risk factor for a numerous diseases, including metabolic disorders and cardiovascular diseases (CVD). Feeding a HFD for a long time results in the occurrence of nonalcoholic fatty liver disease (NAFLD) (18). Recent studies have suggested that a fundamental role in development of these disorders is played by oxidative stress (19). Oxidative stress, being one of the key pathophysiological mechanisms in liver disease associated with obesity, may also serve as a predictor of CVD (18,20). Due to its significant role in disease development, increased oxidative stress remains a potential attractive target for prevention and therapy of adverse HFD and ovariectomy effects. The impact of HFD and estrogen deficiency on oxidative stress can be reduced by regular physical activity (21,22) and intake of phytochemical-rich foods or supplements (19,23). Recently, numerous in vitro and animal studies have provided evidence that polyphenols may be protective against oxidative-triggered pathologies (24,25).The aim of this study was to estimate the effect of HFD on the oxidative and antioxidative status in the liver of ovariectomized (OVX) rats, and to investigate the possible ameliorating effect of lifestyle modifications, such as physical activity or consuming functional foods – cereal selenized onion biscuits (SOB) with bioactive complex – on oxidative damage in the liver.     

Single acute stress-induced progesterone and ovariectomy alter cardiomyocyte contractile function in female rats

Aim

To assess how ovarian-derived sex hormones (in particular progesterone) modify the effects of single acute stress on the mechanical and biochemical properties of left ventricular cardiomyocytes in the rat.

Methods

Non-ovariectomized (control, n = 8) and ovariectomized (OVX, n = 8) female rats were kept under normal conditions or were exposed to stress (control-S, n = 8 and OVX-S, n = 8). Serum progesterone levels were measured using a chemiluminescent immunoassay. Left ventricular myocardial samples were used for isometric force measurements and protein analysis. Ca²⁺-dependent active force (F_active), Ca²⁺-independent passive force (F_passive), and Ca²⁺-sensitivity of force production were determined in single, mechanically isolated, permeabilized cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were analyzed by sodium dodecyl sulfate gel electrophoresis using protein and phosphoprotein stainings.

Results

Serum progesterone levels were significantly increased in stressed rats (control-S, 35.6 ± 4.8 ng/mL and OVX-S, 21.9 ± 4.0 ng/mL) compared to control (10 ± 2.9 ng/mL) and OVX (2.8 ± 0.5 ng/mL) groups. F_active was higher in the OVX groups (OVX, 25.9 ± 3.4 kN/m² and OVX-S, 26.3 ± 3.0 kN/m²) than in control groups (control, 16.4 ± 1.2 kN/m² and control-S, 14.4 ± 0.9 kN/m²). Regarding the potential molecular mechanisms, F_active correlated with MyBP-C phosphorylation, while myofilament Ca²⁺-sensitivity inversely correlated with serum progesterone levels when the mean values were plotted for all animal groups. F_passive was unaffected by any treatment.Conclusion Stress increases ovary-independent synthesis and release of progesterone, which may regulate Ca²⁺-sensitivity of force production in left ventricular cardiomyocytes. Stress and female hormones differently alter Ca²⁺-dependent cardiomyocyte contractile force production, which may have pathophysiological importance during stress conditions affecting postmenopausal women.The relation between stress, gender, and cardiovascular diseases is well established (1-4). Some of the known risk factors for cardiovascular disease such as smoking, unhealthy diet, and behavioral and psychosocial stress have deleterious effects on the cardiovascular system via activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis (5-8). Acute restraint stress is a preferred and widely used method to induce physical stress in animal models (9). Moreover, restraint and immobilization are important as models for psychological stress, which was shown to adversely affect ovarian function (10) and to play a pivotal role in the pathomechmanism of Takotsubo (stress) cardiomyopathy in postmenopausal women (11).Gender is a very important factor in the development of cardiovascular diseases. Premenopausal women have better lipid profile, endothelial function (12), and a lower risk to develop coronary artery disease and myocardial infarction (MI) than men. These advantages of female gender, however, are abolished after menopause, which is associated with increased prevalence of left ventricular (LV) hypertrophy, decreased LV ejection fraction, and LV contractility (13). One of the explanations for the distinct myocardial responses is the cardioprotective effect of female sex hormones (eg, estrogens) (14,15).Progesterone performs several actions on the heart: it exerts an antiarrhythmic effect by accelerating cardiac repolarization (16) and has a preventive role in ischemia-reperfusion injury via reducing inflammatory response (17). It has been shown to inhibit cardiomyocyte apoptosis (18), induce vasodilation, and reduce blood pressure via increasing nitric oxide (NO) levels in normotensive and hypertensive patients (19). Importantly, progesterone is produced by the both ovaries and the adrenal gland: Moreover, the adrenal progesterone content is similar or even larger than that in the ovaries (20). Adrenal progesterone production and secretion increase along with corticosterone regardless of gender and estradiol under stress conditions (21). Progesterone, being an indirect precursor of cortisol (22), increases in response to adrenocorticotrophic hormone (ACTH) stimulation (23).In the heart, there are multiple estrogen hormone receptor types (24). The expression of aromatase in the heart suggests that estrogen may be synthesized also within the cardiomyocyte to exert autocrine/paracrine actions (25). Myocyte contractility seems to be modulated by systemic estrogen levels and altered in cardiomyocytes derived from ovariectomized (OVX) rats (26). In particular, myofilament Ca²⁺-sensitivity is increased in isolated myofibrillar preparations from OVX rats, and restored to the basal levels with estrogen supplementation (27,28).Activation of the sympathetic nervous system plays a central role in the regulation of cardiomyocyte contractile function and myofilament Ca²⁺-sensitivity through beta-adrenergic receptor stimulation, activating the protein kinase A (PKA). PKA-mediated phosphorylation of Ca²⁺-handling and myofilament proteins (myosin binding protein-C [MyBP-C], troponin I [TnI], titin) were shown to alter cardiomyocyte contractile function (29,30). It has been suggested that female cardiomyocytes operate at lower levels of intracellular Ca²⁺ than those of males, particularly under inotropic conditions (31). This difference in Ca²⁺ homeostasis may be related to the fact that estrogen suppresses the L-type Ca²⁺ current (32,33) and may reduce the amount of Ca²⁺ released from the sarcoplasmic reticulum (SR) (34), which was shown to be larger in myocytes from OVX rats (35). Not only cardiomyocyte contraction, but relaxation may also be affected by estrogen via altered Ca²⁺ re-uptake into the SR and modified Ca²⁺ efflux via increased sarcolemmal Na⁺/Ca²⁺ exchange (36). Interestingly, despite similar SR Ca²⁺ content in males and females (37), studies using OVX models report conflicting results concerning changes in the expression and activity of the SR Ca²⁺-ATPase and its regulator protein phospholamban (38-41). Much less is known about the possible effect of progesterone on cardiomyocyte contractile function. We hypothesized that progesterone affected force production of single isolated cardiomyocytes. Therefore, in the present study we aimed to investigate how sex hormones (particularly progesterone) and single acute restraint stress altered cardiomyocyte contractile function and to identify the consequent posttranslational myofilament protein modifications in OVX rats.     

Prognostic value of serum nicotinamide phosphoribosyltransferase in patients with bladder cancer

Aim

To analyze the serum nicotinamide phosphoribosyltransferase (Nampt) level and its prognostic value in bladder cancer (BC).

Methods

The study included 131 patients with transitional cell BC and 109 healthy controls from the West China Hospital of Sichuan University in the period between 2007 and 2013. Nampt concentration in serum was measured by commercial ELISA kits for human Nampt.

Results

The serum Nampt protein level in patients with BC (mean ± standard deviation, 16.02 ± 7.95 ng/mL) was significantly higher than in the control group (6.46 ± 2.08 ng/mL) (P < 0.001). Serum Nampt level was an independent prognostic marker of non-muscle-invasive BC, with a higher serum Nampt level (>14.74 ng/mL) indicating shorter recurrence-free survival rate (hazard ratio = 2.85, 95% confidence interval, 1.01-8.06; P = 0.048).

Conclusion

Our results suggest that serum Nampt level may serve as a biomarker of BC and an independent prognostic marker of non-muscle-invasive BC.Bladder cancer (BC) is the ninth most common cancer diagnosis worldwide (1) and the most expensive cancer to treat (2). Among men it is the fourth most common cancer, with incidence four times higher than in women (3). In China, BC caused 17 365 deaths in 2005, with a steady increase in mortality between 1991 and 2005 (4). Of newly diagnosed BC cases, 70%-80% will present with non-muscle-invasive disease, 50%-70% will recur despite endoscopic and intravesical treatments, and 10%-30% will progress to muscle-invasive disease (5,6). Most recurrences occur within 5 years (7). Therefore, to develop improved, more effective prevention and treatments there is a need to find new biomarkers of tumorigenesis and prognosis of BC.Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the mammalian NAD⁺ biosynthesis of a salvage pathway (8). Previous studies have shown that it is significantly increased in primary colorectal cancer (9-11), lung cancer (12), breast cancer (13), prostate cancer (14) and gastric cancer (15). Thus, Nampt may be a good biomarker of malignant potential and stage progression (12,16). Our previous study revealed that genetic variants in NAMPT may predict BC risk and prognosis (17). In the present study, we analyzed the serum Nampt level and its prognostic value in BC.     

Shear-wave sonoelastographic features of invasive lobular breast cancers

AimTo evaluate shear-wave elastographic (SWE) and related gray-scale features of pure invasive lobular breast carcinoma (ILC) and compare them with invasive ductal breast cancers (IDC).MethodsQuantitative SWE features of mean (El-mean), maximum (El-max), minimum (El-min) elasticity values of the stiffest portion of the mass, and lesion-to-fat elasticity ratio (E-ratio) were measured in 40 patients with pure ILC and compared with 75 patients with IDC. Qualitative gray-scale features of lesion size, echogenicity, orientation, and presence of distal shadowing were determined and compared between the groups.ResultsILC were significantly larger than IDC (P = 0.008) and exhibited significantly higher El-max (P = 0.015) and higher El-mean (P = 0.008) than IDC. ILC were significantly more often horizontally oriented, while IDC were significantly more often vertically oriented (P < 0.001); ILC were significantly more often hyperechoic than IDC (P < 0.001). Differences in stiffness between ILC and IDC determined by quantitative SWE parameters were present only in small tumors (≤1.5 cm in size), ie, small ILC had significantly higher El-max (P = 0.030), El-mean (P = 0.014), and El-min (P = 0.045) than small IDC, while tumors larger than 1.5 cm had almost equal stiffness, without significant differences between the groups.ConclusionSpecific histopathologic features of ILC are translated into their qualitative sonographic and quantitative sonoelastographic appearance, with higher stiffness of small ILC compared to small IDC. Gray-scale and sonoelastographic features may help in diagnosing ILC.Invasive ductal cancer (IDC) is the most common breast cancer, while invasive lobular cancer (ILC) is the second most common and accounts for 6%-12% of breast cancers (1-3). ILC differs considerably from IDC by having a unique pathological growth pattern, the so called Indian-file pattern, with sheets of single-cell layers growing along the Cooper ligaments, ductuli, and other breast structures, resembling a spiderweb that diffusely spreads in the breast, producing minor desmoplastic reaction (4,5). This spiderweb-like growth is reflected in imaging features of ILC, as well as in its clinical presentation (6). IDC usually clinically manifests as a firm lump, while ILC usually manifests as a palpable thickening and skin or nipple retraction (3,5). ILC has increased tendency for multifocality and multicentricity, a higher risk of bilateral breast cancer (20%-29%), and older age at onset (7,8). Lymph node metastases are less common in ILC than in IDC of equal size, because ILC tumor cells lack cellular atypia and often have low mitotic rate (9). ILC has the propensity to metastasize to the chest, peritoneum, retroperitoneum, and pelvis (10).Because of its growth pattern of mass infiltrating surrounding tissues, IDC is much more easily detected than ILC also on mammography. ILC has higher false-negative mammographic rates than IDC, since ILC may be invisible or may have quite low mammographic density, and microcalcifications are uncommon (6,11). Due to the higher propensity for multicentric and bilateral lesions, it is generally considered that patients with ILC should be referred to preoperative breast MRI, the best imaging modality to evaluate the tumor extent, while the benefit for preoperative MRI in IDC has not yet been proven (12,13). Fine-needle aspiration is not as sensitive for the diagnosis of ILC as it is for IDC, and core-biopsy should be performed when ILC is suspected, even in cases of palpable lesions (14,15). ILC is associated more often than IDC with positive margins on surgical excision and is more often treated with mastectomy, because of the large size at diagnosis and underestimation of tumor extent with conventional imaging (16).Ultrasound of the breast is widely used in the diagnosis of breast cancer, usually after mammography, and most image-guided core biopsies of breast lesions are routinely performed under the sonographic guidance (17,18). Ultrasound is highly operator-dependent, much more than mammography or MRI. The quality of ultrasonic equipment and transducers is variable, suboptimal examinations are common, and interobserver variability is high; sensitivity of ultrasound in detection of ILC is reported in the range of 68%-88% (6,12,19).Sonoelastography is a relatively new ultrasonographic method, which may help in the detection and differentiation of benign and malignant breast lesions (18,20). Strain elastography allows qualitative estimation of the breast lesion stiffness, while shear-wave elastography (SWE) allows quantification of lesion stiffness in kilopascals (kPa) (18). Multicentric studies found that SWE features can help discriminate breast cancers and benign breast lesions, and breast cancers among themselves (20-22). It was also shown that some IDC, like triple negative breast cancers, differ in their stiffness compared to other IDC (23). Studies evaluating some SWE features of invasive cancers were done in a small number of patients with ILC, but to the best of our knowledge none so far has provided values specific for a larger, homogeneous group of patients with pure ILC (24,25).The aim of this single-center study was to evaluate and establish SWE and related conventional sonographic features of pure ILC of the breast in a group of 40 patients, and to compare these features with the most common invasive breast cancer, IDC. SWE features within ILC group were also correlated with tumor size, extent, histologic grade, and the presence of nodal metastases.