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Analiza mikrostrukture prolaznih fetalnih zona i segmenata bijele tvari ljudskoga mozga histološkim metodama i magnetskom rezonancijom [Microstructural analysis of transient fetal zones and white matter segments of human brain using histological methods and magnetic resonance imaging]
Get PDFThe development of human brain axonal pathways is a complex process where transitional fetal zones and white matter segments play an important role due to the various spatio-temporal frames of intense growth and the consequent specific sensitivity to the harmful factors during development.
The aim of this thesis was to define the microstructural changes of the white matter segments, for the purpose of better correlation of MRI with clinical parameters in neurodevelopmental disorders.
This study included postmortem brains (fetal/early postnatal period) treated with histological, immunohistochemical and MRI in vitro methods (40 samples in total). In vivo MR images were used in qualitative (12 fetuses in utero, 49 premature infants) and FA-ADC analysis at the (corrected) term-age (7 newborns, 52 premature infants) and at the second year of life (31 subjects).
The histological/MRI analysis of the prenatal/perinatal development of the white matter segments reveals maturational specificity of the second white matter segment, especially the differences between premature and full term infants. The FA and ADC values follow the histological development of the segments, pointing to their differentiation in radial direction, from cerebral ventricles to pial surface, distinguishing groups of neonates between themselves and in comparison with the control group at the corrected term-age, with the tendency of reducing the differences towards the second year of life. Groups with and without perinatal lesions visible on structural MRI differ in the ADC values in the second year of life
The most complex system of commissural, projection and associative fibers is present in the sagittal strata, characterized by particular MR signal intensity changes, which makes it the potential biomarker of perinatal neurorisk. Knowledge of histological/MRI development of the white matter segments has potential for application during routine brain imaging analysis
Skin autoimmunity might be associated with increased efficacy of atezolizumab in metastatic urothelial carcinoma: a case report
Get PDFPrimjena balona s otpuštanjem lijeka u postraničnu granu bifurkacije koronarnih arterija [Use of drug-eluting balloons in side branch of bifurcation lesions on coronary arteries]
Get PDFDespite the progress and development of interventional cardiology, treatment of
bifurcation lesions is still nonoptimal and presents one of the most demanded interventions with
a higher proportion of complications, short-term and long-term unwanted events.
The aim of this study was to compare the angiographic results of drug-eluting balloon
(DEB) in the side branch of coronary artery bifurcations to the angiographic results using the
drug-eluting stent (DES) or provisional stenting, primarily by comparing the degree of in-stent
restenosis and late luminal loss, at least six months after the intervention. The study was defined
as a prospective single-center study involving patients with true bifurcation lesions that affect
both the main and side branch. 60 patients were divided into three groups: DES-DEB, DESDES,
and DES with provisional stenting.
Overall, the median age was 67 years (47-84), with 76.6% male patients. The coronary
angiography indication was stable angina pectoris in 77% of patients and unstable angina in
23% of patients. There were no statistically significant differences in clinical and demographic
characteristics, nor cardiovascular risk factors among groups. No patient has experienced a
major adverse event, counted by the death of a cardiovascular cause or a myocardial infarction.
Target lesion revascularization with the repeated intervention was recorded in two patients in
the second, and two in the third group due to unstable angina while not observed in the first
group. A statistically significant increase in diameter of the side branch was recorded in the first
group from the period of the procedure to the control coronary angiography (0.90 mm), while
in the second and third group there was a lumen loss (0.10 mm and 0.20 mm). Differences in
initial values of the narrowest lumen diameter of the side branch stenosis between the groups
did not exist. After the intervention, the narrowest lumen diameter was higher in the second and
third group compared to the first group, with the loss of difference observed on follow-up
between the first and the second group (2.25 vs. 2.22 mm; p = 0.607). Also, the narrowest lumen
diameter in the first group on follow-up was significantly higher concerning the third group
(2.25 vs. 1.74 mm; p = 0.0003).
The data obtained show the superior six-month angiographic results of using DEB in
the side branch segment to the provisional technique and the non-inferiority to DES use
Utjecaj multimodalne analgezije metamizolom na poslijeoperacijsku bol i ranu rehabilitaciju u bolesnika nakon ugradbe totalne endoproteze koljena [The influence of multimodal analgesia with metamizole on the postoperative pain and early rehabilitation in patient with total knee replacement]
Get PDFINTRODUCTION: Pain is a major limiting factor of early rehabilitation after total knee replacement (TKR). Pain after TKR is described as severe and very severe and it requires the use of strong analgesics in the treatment of pain. Multimodal analgesia involves a combination of two or more drugs that will treat the central and peripheral component of pain, with the aim of better control of pain with less side effects of the medication. Data regarding the optimal drug combination regimen during the first four weeks of rehabilitation in patients after TKR are insufficient. -----
OBJECTIVES: The aim of this study is to demonstrate equally effective control of the acute postoperative pain and functional outcome in patients receiving metamizole as compared to meloxicam in multimodal analgesic regimens during the first four weeks of rehabilitation after TKR. The specific objective were to determine whether the differences between the groups in the functional outcome and patient satisfaction, and to test the correlation of the pain intensity and the size of the postoperative hematoma with the knee motion range during the 28 days of rehabilitation. -----
MATERIALS AND METHODS: This prospective open randomized study included patients hospitalized for the TKR because of severe knee osteoarthritis. From the first postoperative day (POD1) to POD20, all patients regularly received oxycodone in therapeutic dose, with one group receiving meloxicam, and the other group metamizole in therapeutic doses. As an additional analgesic, paracetamol and tramadol were used at the patient's request throughout the whole study period. At the examination before surgery were recorded the general demographic dana of the patient, the intensity of pain at rest, in activity and during the night, the level of general satisfaction, flexion and extension of the knee and the suprapatellar knee circumference. These variables are measured daily during rehabilitation. The total amount of additional analgesics was recorded during the study period. Prior to surgery and after 4 weeks of rehabilitation, specific questionnaires (WOMAC, KSS) and the length of the walk (6MWT) were measured. -----
RESULTS: In our study 135 patients were included between September 2013. and December 2014. Data were analyzed for 127 divided into two study groups, 63 in metamizole and 64 in the meloxicam group. During the 4 weeks, daily measured pain intensity in both groups was comparable and were reduced proportionately over time. The flexion and extension after initial upward dynamics lost the achieved values at the end of the first and at the beginning of the second week to restart again at the end of the second week. Pain during the first two weeks after surgery largely affects the achievement of flexion, but only after 10th day of rehabilitation. Our findings indicate that postoperative hematoma progression is associated with loss of knee movement. After 4 weeks of rehabilitation, we did not find differences in the achieved functional outcome, the intensity of pain or the satisfaction level between the observed groups of patients. -----
CONCLUSION: Postoperative pain during the first 4 weeks of rehabilitation after TKR was equally well treated in patients receiving metamizole as compared to meloxicam in multimodal analgesic regimens, which was confirmation of the hypothesis. Proper pain control and bleeding prevention measures in the knee area can accelerate recovery during the first month of rehabilitation after TKR
Biološke značajke mezenhimskih matičnih stanica umnoženih in vitro u mediju s lizatom ljudskih trombocita [Biological properties of mesenchymal stem cells expanded in vitro in medium with human platelet lysate]
Get PDFMesenchymal stem cells (MSC) are nonhematopoietic multipotent cells that can differentiate
into tissues of mesodermal origin. Due to their ability to induce immunological tolerance in
the recipient, MSC have been utilized in the treatment of various hematological and immuneand
inflammation-mediated diseases. The clinical application of MSC implies prior in vitro
expansion that usually includes use of fetal bovine serum (FBS) which is associated with a
risk of transmitting infectious agents and immunizing events. Furthermore, the varied tissue
sources, methodologies of cell preparations and culture conditions used by different MSC
research and clinical groups resulted in ambiguities and inconsistencies in this field.
Aim of this study was to evaluate the effect of platelet lysate (PL) on biological properties of
MSC expanded in vitro in comparison to the FBS culture condition.
The results showed that the cells cultured in different conditions had comparable
imunophenotype, clonogenic potential and differentiation capacity. However, MSC growth
was significantly enhanced in the presence of PL, which was demonstrated by higher number
of cumulative population doublings (CPDs) and shorter population doubling time (PDT).
Furthermore, MSCs cultured in the presence of PL were able to cause a 66.9% reduction of
mitogen-induced lymphocyte proliferation. Chromosome aberrations observed in the PL
condition were transient and did not have selective advantage in the culture system.
In conclusion, this research confirmed that substitution of FBS in the MSC expansion media
with PL would enable the yield of clinically relevant numbers of MSC within shorter time
period and improve safety and quality of the cell products
Molecular mechanisms of neurodegeneration related to C9orf72 hexanucleotide repeat expansion
Get PDFTwo clinically distinct diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), have recently been classified as two extremes of the FTD/ALS spectrum. The neuropathological correlate of FTD is frontotemporal lobar degeneration (FTLD), characterized by tau-, TDP-43-, and FUS-immunoreactive neuronal inclusions. An earlier discovery that a hexanucleotide repeat expansion mutation in chromosome 9 open reading frame 72 (C9orf72) gene causes ALS and FTD established a special subtype of ALS and FTLD with TDP-43 pathology (C9FTD/ALS). Normal individuals carry 2-10 hexanucleotide GGGGCC repeats in the C9orf72 gene, while more than a few hundred repeats represent a risk for ALS and FTD. The proposed molecular mechanisms by which C9orf72 repeat expansions induce neurodegenerative changes are C9orf72 loss-of-function through haploinsufficiency, RNA toxic gain-of-function, and gain-of-function through the accumulation of toxic dipeptide repeat proteins. However, many more cellular processes are affected by pathological processes in C9FTD/ALS, including nucleocytoplasmic transport, RNA processing, normal function of nucleolus, formation of membraneless organelles, translation, ubiquitin proteasome system, Notch signalling pathway, granule transport, and normal function of TAR DNA-binding protein 43 (TDP-43). Although the exact molecular mechanisms through which C9orf72 repeat expansions account for neurodegeneration have not been elucidated, some potential therapeutics, such as antisense oligonucleotides targeting hexanucleotide GGGGCC repeats in mRNA, were successful in preclinical trials and are awaiting phase 1 clinical trials. In this review, we critically discuss each proposed mechanism and provide insight into the most recent studies aiming to elucidate the molecular underpinnings of C9FTD/ALS
Impact of obesity on ovarian reserve [Utjecaj debljine na ovarijalnu rezervu]
Get PDFObesity is the most frequent chronic disease. In the Western world and in these areas the incidence of overweight and obesity is 50–60%. In parallel with an increase in obesity over the past 30 years, there is also an increase in infertility incidence. Obesity is often associated with PCOS and the combined pathophysiology can cause a variety of metabolic and reproductive disorders. Obesity is also associated with subfertility and infertility in men and women. -----
Aim of the study:
The aim of this study was to identify the effects of obesity and central obesity on ovarian reserve. We also tried to identify the correlation of obesity with changes in reproductive hormones, which could be a cause of subfertility. We separately investigated the effects of obesity and PCOS on reproductive capacity. Ovarian reserve markers (AMH, AFC and ovarian volume) were investigated according to the body mass index of participating patients. -----
Methodology and methods:
In this prospective cross-sectional cohort study on 182 women grouped in 3 categories according to body mass index (normal weight, overweight and obese), 52 had PCOS. We determined and compared hormone and ovarian reserve results in each BMI patient group. -----
Statistical analysis:
Statistical analysis was performed by using the statistical package SPSS 17.0. Data is reported as mean±standard deviation. Student’s t test/ANOVA was used to compare the means of parametric data and the Man-Whitney test / the Krusckal Wallis test to compare non-parametric data. The Chi square test were used to analyze categorical outcomes. For statistical significance the value of the factor alpha is ≤ 0.05. ----- Results:
In the investigated sample of infertile patients, 35% were normal-weight women, and 65% were overweight or obese. Of that number, 28.6% had PCOS, while the prevalence of abnormal BMI in that patient group was 71%. Central obesity was identified in 68% of obese patients and in 90% of obese PCOS patients.
Prolongs of the menstrual cycle, oligomenorrheae, anovulation, hyperandrogenism are more presente in obesity and PCOS patients than in obese respectivly control group.
Obesity does not lower AMH, AFC and OV levels. -----
Conclusion:
Since the relationship between the indicators and insulin resistance has already been proven, our results emphasize a high correlation of obesity, central obesity and PCOS with subfertility and long-term infertility. Positive or negative effects of excessive adipose tissue on ovarian reserve markers were not identified
Termičke promjene tijekom cijeljenja prijeloma distalnoga radijusa [Thermal changes during healing of distal radius fractures]
Get PDFBone healing process is very complex. Increase in blood flow around the fracture during the healing process increases the temperature. Infrared thermography is a method of measuring body temperature that can detect thermal changes.
A prospective study was conducted on 50 patients with the aim of investigating thermal changes during the healing of distal radius fractures and on 30 healthy volunteers for the purpose of method validation. The Flir ThermaCam B2 (Flir System Inc., Oregon, SAD) was used for all measurements. Thermographic recordings were made at one, three, five, 11 and 23 weeks after fracture. In healthy volunteers, thermographic recordings were made before plaster of Paris immobilization and 24 hours later. The contralateral hand was used for comparison. Patients' x-rays were also analyzed and fracture healing was classified by Hammer and RUSS methods.
Significant temperature differences between patients with fractures and healthy volunteers at one, three, five and 11 weeks after the fracture were found, while at 23 weeks there was no temperature difference. The highest temperature differences were at the 3rd week after fracture and then the temperature difference gradually decreased. The dynamics analysis of thermal changes clearly demonstrated the influence of time on temperature changes between broken and healthy hands. Patients with repositioned fractures had a significant difference in temperature relative to those without repositioning and also a lower chance that fracture will heal in five weeks. Patients with a lower temperature difference and a lower drop in temperature had a greater chance of healing.
Infrared thermography is a method that is not harmful or invasive and can be used as an additional method of fracture healing follow up in combination with x-ray and clinical examination
Izraženost Wnt 4 u presađenim bubrezima [Expression of Wnt 4 in transplant kidneys]
Get PDFWith the gradual development of modern medicine the overall survival and quality of life of patients with chronic kidney disease significantly improved. Kidney transplantation significantly enhanced the treatment of end-stage renal disease patients. However, many transplanted kidneys are lost due to chronic graft changes caused by immunosupression therapy or occurence of late chronic immunologic response. The family of Wnt (wingless- type MMTV integration site family) genes are constituted of 19, till now, described members. Some of this proteins are present in kidney development but also in the process of kidney injury and reparation. Due to this published results it is assumed that the same molecules responsible for the regulation of nephrogenesis also participates in the patophysiology of tubulointerstitial kidney disease. It is still not clear which Wnt gene is responsible for protection and which for damage especially in transplanted kidneys. The aim of this study was to analyze whether Wnt 4 expression is increased in transplanted kidneys compared to healthy kdiney samples and is it dependable of different causes of graftectomies. In this study we have included 59 kidney transplanted patients from deceased donors and 24 nephrectomized patients due to localised kidney tumours as a control group. The obtained results did not confirmed our hypothesis. On the contrary, the Wnt 4 expression was significantly lower in the kidney transplanted patients group compared to healthy kidney tissue samples which was strongly correlated with age. Although the Wnt 4 expression was correlated with higher age, its most independent and significant correlation was with longer cold ischemia time. This are, at least to our knowledge, the first results which reported higher Wnt 4 expression and better kidney graft survival and its possible role as an factor in kidney graft regeneration especially in prolonged ischemia time and acute tubular necrosis. These results emphasize the importance on future studies of different Wnt receptors agonists as a novel therapy in treating tissue ichemia injuries
Povezanost insuficijencije konvergencije očnih jabučica sa sindromom poremećaja pažnje u djece [Relationship between convergence insufficiency and attention deficit hyperactivity disorder]
Get PDFADHD syndrome (attention deficit/hyperactivity disorder) is a developmental disorder of self-control. It consists of problems with attention span, impulse control and activity level. One of the symptoms is a disturbance in reading and writing, as well as a visual disturbance that a child or a parent cannot precisely describe. That state is often recognized in preschool and school age as the expectation of abilities that consist of longer concentration and better attention arise.
Convergence insufficiency is an inability to maintain a binocular function while working at near distance; it is characterized by a patient’s inability to converge eyes as the object moves closer from a distance to the near and/or the inability to maintain the near point of convergence. It leads to a loss of binocular vision and results in reading difficulties or other near tasks impairment. We noticed that children diagnosed with ADHD had a high incidence (35.6%) of convergence insufficiency (CI). The symptoms of these two conditions can overlap and both can interfere with reading and learning abilities. The aim of our study was to evaluate the relationship between ADHD and CI, measuring CI before and after the orthoptic treatment and establish whether improving of convergence in patients with ADHD simultaneously improves concentration. Furthermore, we wanted to determine whether improvement of near point of convergence (NPC) and binocular vision after orthoptic exercises have any impact on children and adolescents diagnosed with Attention Deficit/Hyperactivity Disorder (ADHD) and convergence insufficiency (CI).
Results of the study showed that orthoptic therapy enhanced the NPC and improved stereovision in patients with ADHD. Results of d2 Test implied that attention had enhanced as well, and we found a correlation between the improvement of convergence and the improvement of attention. The results showed that only 12,2% of the attention improvement cases can be explained as a direct result of orthoptic therapy