University of Zagreb Medical School Repository
University of Zagreb Medical School RepositoryNot a member yet
2851 research outputs found
Sort by
Fenotipska i funkcijska karakterizacija osteoklastnih progenitora u bolesnika s reumatoidnim artritisom [Phenotypic and functional characterization of osteoclast progenitors in patients suffering from reumathoid arthritis]
Get PDFRheumatoid arthritis (RA) is a chronic joint disease marked by persistent inflammation and joint destruction. The mechanisms leading to joint destruction involve differentiation and activation of osteoclasts. Peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCP) which contribute to osteoresorption in inflammatory arthritides, and are influenced by cytokine and chemokine milieu.
This work aimed to compare the phenotype, frequency and differentiation potential of OCPs in the peripheral blood and synovial fluid of patients suffering from RA and psoriatic arthritis (PsA) to those of healthy controls and to define importance of chemokine signals for migration and activation of OCPs.
The results showed that the OCP population was moderately enlarged among PB cells in RA and correlated with levels of TNF-α, rheumatoid factor, CCL2 and CCL5. Compared to PB, RANK+ subpopulation was expanded in SF and correlated with the number of tender joints. PsA patients could be distinguished by increased RANK expression rather than total OCP population. OCPs from arthritic patients had higher expression of CCR1, CCR2, CCR4, CXCR3 and CXCR4. In parallel, RA patients had increased levels of CCL2, CCL3, CCL4, CCL5, CXCL9 and CXCL10, with significant elevation in SF vs PB for CXCL10. Subset expressing CXCR4 positively correlated with TNF-α, bone resorption marker and rheumatoid factor, and was reduced in patients treated with DMARD. CCR4+ subset showed significant negative trend during anti-TNF treatment. CCL2, CCL5 and CXCL10 had similar osteoclastogenic effects, with CCL5 showing greatest chemotactic action on OCPs.
In conclusion, this work identified effects of selected chemokines on stimulation of OCP mobilization, tissue homing and maturation. Novel insights into migratory behaviors and functional properties of circulatory OCPs in response to chemotactic signals could open ways to new therapeutic targets in RA
Analysis of pulmonary surfactant by Fourier transform infrared spectroscopy after exposure to sevoflurane and isoflurane
Get PDFPulmonary surfactant, consisting primarily of phospholipids and four surfactant-specific proteins, is among the first structures that is exposed to inhalation anesthetics. Consequently, changes of pulmonary surfactant due to this exposure could cause respiratory complications after long anesthetic procedures. Fourier transform infrared (FTIR) spectroscopy was used to explore the effects of two inhalation anesthetics, sevoflurane and isoflurane, on a commercially available pulmonary surfactant. The research was primarily focused on the effect of anesthetics on the lipid component of the surfactant. Four different concentrations of anesthetics were added, and the doses were higher from the low clinical doses typically used. Recorded spectra were analyzed using principal component analysis, and the Student's t-test was performed to confirm the results. The exposure to both anesthetics induced similar changes, consistent with the increase of the anesthetic concentration. The most pronounced effect was on the hydrophilic head group of phospholipids, which is in agreement with the disruption of the hydrogen bond, caused by the anesthetics. A change in the band intensities of CH2 stretching vibrations, indicative of a disordering effect of anesthetics on the hydrophobic tails of phospholipids, was also observed. Changes induced by isoflurane appear to be more pronounced than those induced by sevoflurane. Furthermore, our results suggest that FTIR spectroscopy is a promising tool in studying anesthetic effects on pulmonary surfactant
Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders
No full textInherited methylation disorders are a group of rarely reported, probably largely underdiagnosed disorders affecting transmethylation processes in the metabolic pathway between methionine and homocysteine. These are methionine adenosyltransferase I/III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. This paper provides the first consensus recommendations for the diagnosis and management of methylation disorders. Following search of the literature and evaluation according to the SIGN-methodology of all reported patients with methylation defects, graded recommendations are provided in a structured way comprising diagnosis (clinical presentation, biochemical abnormalities, differential diagnosis, newborn screening, prenatal diagnosis), therapy and follow-up. Methylation disorders predominantly affect the liver, central nervous system and muscles, but clinical presentation can vary considerably between and within disorders. Although isolated hypermethioninemia is the biochemical hallmark of this group of disorders, it is not always present, especially in early infancy. Plasma S-adenosylmethionine and S-adenosylhomocysteine are key metabolites for the biochemical clarification of isolated hypermethioninemia. Mild hyperhomocysteinemia can be present in all methylation disorders. Methylation disorders do not qualify as primary targets of newborn screening. A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L. There is some evidence that this diet may also be beneficial in patients with S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. S-adenosylmethionine supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency. Recommendations given in this article are based on general principles and in practice should be adjusted individually according to patient's age, severity of the disease, clinical and laboratory findings
Current therapeutic approach to hypertrophic scars
Get PDFAbnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients' expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome
Privrženost, samopoštovanje i emocionalna prilagodba u bolesnica s bulimijom nervozom
Get PDFIntroduction
Attachment theory is one of the most important theoretical frameworks for understanding human relationships and emotion regulation. Attachment represents permanent emotional bond between the child and primary caregiver (Ainsworth et al., 1978), the purpose of which is maintaining proximity to the attachment figure, especially in stressful situations (Bartholomew & Horowitz, 1991). The attachment figure represents a person who provides emotional and physical care and is consistently and continuously present in the child's life, and who invests emotions in the relationship with the child (Pearce, 2009). The mental representations of self and others that a child develops through early experiences with an attachment figure represents the attachment internal working model (Bowlby, 1973). Internal working models of attachment are the foundations for stable and consistent ways in which children and adults perceive themselves and others, interact, interpret information and regulate emotions. Emotional regulation is defined through processes by which individuals affect the emotions that they will experience, when they experience them and how to express them (Gross, 2014). An individual with a negative sense of self and others is not able to adequately regulate their emotional reactions, which can have a significant impact on the psychopathology of eating disorders. Bulimia nervosa is often described as a syndrome of overeating and purging, consists of episodes of binge eating followed by induced vomiting or misuse of laxatives, to be expelled from the body huge amounts of food (Marcinko, 2013). The disorder occurs in approximately 10 women to one man, usually in late adolescence or young adulthood (APA, 2000), and most often between 14 and 25 years of age (Cavanaugh and Ray, 1999). For bulimic patients the typical psychopathology is associated with poor impulse control, such as auto-aggressive and hetero-aggressive behavior, suicide, sexual promiscuity etc. In this paper we will try to explain in detail the nature of the link between insecure attachment, dysfunctional emotional regulation and bulimia nervosa.
Methodology
The study was designed as a cross-sectional with clinical and control group of subjects. The clinical group consisted of 50 patients suffering from bulimia nervosa, treated at the University Hospital Center Zagreb. The control group consisted of 50 female subjects that was characteristically consistent with the clinical group subjects. The study used socio
demographic profile questionnaire, Eating Disorder Inventory 2 (EDI-2; Garner, 1991), The Experiences in Close Relationships-Revised (ECR-R; Brennan, Clark and Shaver, 1998), Difficulties in Emotion Regulation Scale (DERS; Gratz and Roemer, 2004) and SCOFF (Morgan, Reid and Lacey, 1999). The statistical analysis of results utilised methods of descriptive and inferential statistics, and graphical representations of results.
Results
The clinical group subjects achieved significantly higher scores on the anxiety and avoidance dimensions than the control group subjects. The regression model showed itself as statistically significant and was able to explain the 24.6% of the variance of BN symptoms, where anxiety is a statistically significant predictor of BN symptoms , and avoidance does not significantly contribute to the explanation of variance in BN symptoms. The subjects of the clinical group showed significantly more emotional regulation difficulties. Difficulties of emotional regulation represent a statistically significant predictor of symptoms BN and explains 41.3% of variance in BN symptoms. Anxiety, avoidance and emotional regulation are individually shown to be statistically significant predictors in the prediction of group membership, but after including all the variables in the regression model, the contributors to anxiety and avoidance have lost their significance, while emotional regulation proved to be a statistically significant predictor in the prediction of group membership. Hierarchical regression analysis showed the existence of mediation influence of emotional regulation in the relationship of dimensions of attachment and severity of symptoms of BN.
Discussion
The findings are consistent with the assumption that women with BN are expected to show higher level of anxiety and avoidance, suggesting that patients with BN experience close relations through constant vigilance, a sense of fear and worries of possible rejection and abandonment (anxiety), and the discomfort of closeness (avoidance), which is defined as fearful attachment (Hazan and Shaver, 1987). Anxiety is a significant predictor of symptoms of BN, which is associated with lower capacity to regulate emotion, while avoidance in terms of attachment theory is associated with AN, and increased control of emotions. The subjects of clinical group showed significantly more emotion regulation difficulties, and emotional regulation difficulties represent a statistically significant predictor of BN symptoms, which is also consistent with the findings of previous studies suggesting that people who suffer from eating disorders, including BN, reported a higher level of emotional regulation difficulties
(Harrison et al., 2010b; Svaldi et al., 2012), as well as in accordance with the theoretical model according to which emotional regulation difficulties contribute to psychopathology of eating disorders, as well as acting as inappropriate strategies to manage their own emotions (Wilde et al., 2010; Haynos & Fruzzetti, 2011; Wonderlich et al., 2014). Anxiety, avoidance and emotional regulation are individually shown to be statistically significant predictors in predicting whether people belong to clinical or control group, but after inclusion of all the variables in the regression model anxiety and avoidance contributors have lost their importance, while emotional regulation proved to be a statistically significant predictor of group membership. Hierarchical regression analysis showed the existence of mediation influence of emotional regulation in the relationship of attachment dimensions and severity of symptoms of bulimia nervosa. The findings are in line with the mediating model (Tasca et al., 2009), which assumes that attachment affects emotional regulation, which in turn influences eating disorders.
Conclusion
It was found that patients suffering from BN showed significantly higher levels of anxiety and avoidance than control group subjects, suggesting that they experience close relations through constant vigilance, a sense of fear and worries of possible rejection and abandonment (anxiety), and the discomfort of closeness (avoidance), which is defined as fearful attachment. Both dimensions of attachment were significantly positively correlated with the symptoms of BN, but in the same model dimension anxiety emerged as an significant predictor of symptoms BN, while avoidance proved to be an insignificant predictor, indicating that the anxiety is a stronger correlate of BN symptoms. It was also found that subjects who suffer from BN have more difficulties in emotional regulation than women in the control group. Emotional regulation difficulties significantly associated with BN symptoms, and represent a statistically significant predictor of BN symptoms, in the way that those patients with pronounced emotion regulation difficulties show higher levels of BN symptoms. Both dimensions of attachment as well as emotion regulation individually successfully predict whether a person will suffer from BN, but in the same regression model anxiety and avoidance proved to be insignificant predictors, while emotional regulation proved to be a significant predictor. The findings indicate that emotional control correlates stronger with BN, than the dimensions of attachment, and suggest that the anxiety and avoidance are associated with BN because of its association with emotional regulation, while emotional regulation demonstrates a unique relationship with BN. The relationship between variables is explained
through mediation. Conducted hierarchical regression analysis determined the mediation influence of emotional regulation in the relations of attachment and BN, whereby attachment influences emotional regulation strategies, which in turn influences eating disorders
Helicobacter pylori infection and severity of coronary atherosclerosis in patients with chronic coronary artery disease
Get PDFAIM:
Controversy exists concerning the relation between Helicobacter pylori (HP) infection and coronary artery disease (CAD). We aimed to examine the relationship between HP infection and severity of coronary atherosclerosis in patients with chronic CAD. -----
PATIENTS AND METHODS:
A total of 150 patients (109 [73%] men; mean age 62.61±10.23 years) scheduled for coronary artery bypass grafting surgery were consecutively enrolled in the cross-sectional study. According to rapid urease test and/or gastric biopsy samples stained with hematoxylin and eosin and according to Giemsa, patients were classified as HP positive (n=87; 58%) or HP negative (n=63; 42%). Coronary angiograms were scored by quantitative assessment, using multiple angiographic scoring system: 1) vessel score (number of coronary arteries stenosed ≥50%), 2) Gensini score (assigning a severity score to each coronary stenosis according to the degree of luminal narrowing and its topographic importance) and 3) angiographic severity score (number of coronary artery segments stenosed ≥50%). -----
RESULTS:
In comparison to HP-negative patients, HP-positive patients were more frequently hypertensive (P=0.014), had higher values of systolic (P=0.043) and diastolic (P=0.005) blood pressure and total cholesterol (P=0.013) and had lower values of high-density lipoprotein-cholesterol (HDL-C; P=0.010). There were no significant differences between the groups in the severity of coronary atherosclerosis: vessel score (P=0.152), Gensini score (P=0.870) and angiographic severity score (P=0.734). -----
CONCLUSION:
It is likely that HP infection is not a risk factor for the severity of coronary atherosclerosis in chronic CAD patients
A rapid biochemical and radiological response to the concomitant therapy with temozolomide and radiotherapy in an aggressive ACTH pituitary adenoma
Get PDFBackground and Importance: In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. ----- Clinical Presentation: We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. ----- Conclusion: Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma
Utjecaj BPC 157 na cijeljenje frakture, ektopičnu kost i heterotopnu osifikaciju u štakora [The effect of BPC 157 on fracture healing, ectopical bone and heterotopic ossification in the rat]
Get PDFINTRODUCTION
Heterotopic ossification denotes bone formation in extraosseus tissues, it is most commonly acquired in nature. It’s development follows extremity injuries, burns or spinal cord injuries and is often linked to a significant functional impairment for the patient. Although it can arise after a multitude of injuries, in our clinical practice it is often the result of fractures about the elbow, where it is functionally of paramount importance. BPC 157 was shown as a potent agent in a myriad of experimental models where complex healing was required to restore function, therefore we think that the research of the effect of BPC 157 is worthwhile.
MATERIALS AND METHODS
We based our experiment on the model described by Zotz et al. and was performed on Wistar Albino male rats, kept in standard conditions. We modified the aforementioned model by adding a fracture and implanting a fragment of bone into the thigh of the hind leg, this gave us two models for which the design of the study is identical. BPC 157 was administered as a 99% pure solution in drinking water and applied in two dosages 10μg/kg and 10ng/kg administered per orally. The study was conducted as co-treatment and post-treatment, to each group we randomly assigned 5 animals in co-treatment and 6 in post-treatment, 96 animals per model, 192 animals in total. The animals were euthanized on the 7th, 14th, 21st and 28th day in co-treatment and 42nd and 56th day in post-treatment, on the same day functional measurements were carried out, which included measurement of contracture of the operated leg, extensor postural test (EPT), gait analysis, motor function index (MFI). After euthanasia, specimens were collected and classical radiography and histological analysis were performed. Statistical analysis was performed and significance was set at p < 0,05.
RESULTS
The experimental groups showed better fracture healing in the co-treatment, and better nonunion healing in the post-treatment group, ectopic bone resorption was enhanced,
functional impairment lessened and statistical analysis showed significance at p < 0,05. The aforementioned effects were more pronounced in the 10μg/kg dose, although the 10ng/kg dose showed clinically significant improvement. We could not replicate the results of Zotz et al. and achieve development of heterotopic ossification.
CONCLUSION
BPC 157 enhances fracture and nonunion healing, helps to preserve functional integrity of the hind leg postoperatively and helps with ectopic bone resorption
Bilateral ovarian torsion during follow-up for antenatally detected ovarian cysts
Get PDFOvarian torsion is a surgical emergency demanding timely diagnosis and treatment to prevent loss of the ovaries which if happens may result in functional and emotional consequences. Simple (less than 5cm in size) ovarian cysts require follow-up for potential self-resolution. We describe a case of antenatally detected bilateral ovarian cysts that developed bilateral ovarian torsions on follow-up, postnatally