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Osteometrijsko određivanje spola žrtava Domovinskoga rata temeljem dimenzija acetabuluma, aurikularne i retroaurikularne plohe zdjelične kosti [Osteometric sex determination based on dimension of acetabulum, auricular and retroauricular surface of pelvic bone in victims of the War of Independence in Croatia]
Aim: The purpose of this research was to establish osteometric standards for sex determination of skeletal remains of Croats, by measuring acetabula, auricular and retroauricular surface. The skeletal remains included were victims of Croatian War of Independence and they represent contemporary Croatian population. -----
Materials and methods: The material consisted of 100 male and 100 females pelvic bones. Nine variables were measured on the acetabulum, auricular and retroauricular surface using sliding caliper and flexible measuring tape. Measured variables were noted in milimeters and were used in statistical analysis. -----
Results: Measured variables showed significantly higher values in men than in women with the exception of transverse diameter of auricular surface which showed no statistical significant difference between the sexes.
Unifactor analysis showed the transverse acetabulum diameter is the best single variable with the accuracy of sex estimation in 88%.
Four models of discirminant function equations were established. The best accuracy was achieved with model which included six variables when the accuracy of sex estimation was 89%. -----
Conclusion: Satisfactory accuracy can be achieved when using these set standards for Croatian population in sex estimation, both for forensic and legal puproses of identifying skeletal remains
Učinkovitost i nuspojave radioterapije infradijafragmalnih polja u bolesnika s limfomima [The efficancy and the side-effects of infradiaphragmal radiotherapy fields in patients with lymphoma]
Lymphomas are very radiosensitive and radiotherapy (RT) was the first treatment modality that enabled cure. Radiation has been shown to be effective in the treatment of all stages and forms of lymphomas, but there is no data on the efficacy and toxicity of irradiation infradiaphragmaly located lymphomas. This study included 112 patients treated with external beam radiotherapy between January 2003 and December 2014. The median follow-up for all patients is 78.7 months. There were 89.3% of Non-Hodgkin lymphoma patients (71% aggressive and 29% indolent) and 10.7% of patients with Hodgkin lymphoma. Two-year and five-year survival is 80% and 69%. Two-year and five-year survival without relapse is 74% and 59% for all patients. The in-field and out-of-field recurrence rates are 5% and 21% respectively for the entire group. Acute toxicity experienced 43% patients. It was gastrointestinal problems at 26% of patients. Long-term side effects were noticed in 15% of patients, most often due to GI system failure in 5% of patients.
Radiotherapy is an effective and safe treatment option for patients with localized abdominal lymphoma. It provides excellent local disease control and long-term survival with minimal late toxicity. It seems that the benefit of new radiotherapy techniques is lower in infradiaphragmal then supradiaphragmal fields, possibly due to different sensitivity of healthy tissue
Omjer S-adenozilmetionina i S-adenozilhomocisteina i polimorfizmi gena za S-adenozilhomocistein hidrolazu u novorođenčadi s prirođenim srčanim greškama i njihovih majki [Concentration of S-adenosylmethionine, S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase gene polymorphisms in newborns with congenital heart diseases and their mothers]
The congenital heart disease is the consequence of complex interaction of more or less known embryological and genetic factors, the environmental factor in the periconceptional period and the mother's lifestyle habits. One of the possible mechanisms is derangement in methylation pathway, both in mothers and in children. This thesis supports the fact that the low aviability of folic acid or vitamin B12 in the periconceptional period and consequent mother’s hyperhomocysteinemia are associated with the risk of having a child with congenital heart disease. The question is whether homocysteine itself is a risk factor or changes in methylation biomarkers S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) and methylation potential are responsible for a higher incidence of congenital heart disease.
The first hypothesis of this dissertation was that increased plasma concentrations of AdoMet is associated with an increased risk of congenital heart disease, another hypothesis that increased plasma concentrations of AdoHcy is associated with an increased risk of congenital heart disease. The third hypothesis was that newborns with congenital heart disease and their mothers would have decreased methylation ratio compared to referral group. The fourth hypothesis was that newborns with congenital heart disease and their mothers would have a different prevalence of the AHCY rs13043752 and rs41301825 polymorphisms, compared to healthy subjects.
In order to reach goals of this study, we included 127 newborns with congenital heart disease and 103 mothers of newborns with congenital heart disease and measured AdoMet and AdoHcy in their plasma by high performance liquid chromatography tandem mass spectrometry and then calculate their methylation potential. The prevalences of polymorphisms rs13043752 and rs41301825 of the AHCY gene were studied in examined group by sequencing AHCY gene exons 2, 3 and 4.
In the group of newborns with congenital heart disease we have found statistically significant increased AdoMet compared to the referral group. There was no statistically significant difference in the concentration of AdoHcy. Methylation potential in this group was consequently statistically significantly higher. In the group of mothers of newborn with congenital heart disease we have found statistically significant increased of AdoHcy compared to the referral group, but no statistically significant difference in the concentration of AdoMet. Methylation potential was statistically significantly lower, according to the hypothesis.
Increased concentrations of AdoMet or AdoHcy measured in our groups of examinees and statistically significant differences in the methylation potential values in our groups of examinees compared to the reference values point to changed methylation processes which can contribute to the pathogenesis of congenital heart disease. It is explained in the dissertation how changes in methylation potential and the increased concentration of AdoMet and AdoHcy may affect the methylation processes within the cell and contribute to increased risk of congenital heart disease.
There was no statistically significant difference in the prevalence of polymorphisms rs13043752 and rs41301825 of the AHCY genes in the study groups compared to healthy subjects, suggesting that they are not associated with increased risk of congenital heart disease.
The results of this study indicate that methylation disorders are involved in pathogenesis of congenital heart diseases. Further studies are needed to elucidate the exact mechanism by which disturbed methylation leads to changes in epigenetic programming of genes and other recipients of the methyl group and consequently to higher risk of congenital heart disease and changes in the programming of methylation processes in the fetus
Best practices for long-term monitoring and follow-up of Alemtuzumab-Treated MS patients in real-world clinical settings
Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in the absence of continuous treatment and with a consistent safety profile. There is an increased incidence of autoimmune events in patients treated with alemtuzumab (mainly thyroid events, but also immune thrombocytopenia and nephropathy), which imparts a need for mandatory safety monitoring for 4 years following the last treatment. The risk management strategy for alemtuzumab-treated patients includes laboratory monitoring and a comprehensive patient education and support program that enables early detection and effective management of autoimmune events, yielding optimal outcomes for MS patients. Here we provide an overview of tools and techniques that have been implemented in real-world clinical settings to reduce the burden of monitoring for both patients and healthcare providers, including customized educational materials, the use of social media, and interactive online databases for managing healthcare data. Many practices are also enhancing patient outreach efforts through coordination with specialized nursing services and ancillary caregivers. The best practice recommendations for safety monitoring described in this article, based on experiences in real-world clinical settings, may enable early detection and management of autoimmune events, and help with implementation of monitoring requirements while maximizing the benefits of alemtuzumab treatment for MS patients
Long-term water sorption and solubility of experimental bioactive composites based on amorphous calcium phosphate and bioactive glass
The aim of this study was to evaluate water sorption and solubility of two series of experimental composites containing amorphous calcium phosphate (ACP) or bioactive glass (BG). Water sorption and solubility were measured for up to 287 days. The surface precipitation of calcium phosphates was evaluated by scanning electron microscopy. The ACP-series showed higher water sorption (223-568 µg/mm3) than the BG-series (40-232 µg/mm3). In contrast, the ACP-series had generally lower solubility (37-106 µg/mm3) than the BG-series (1-506 µg/mm3). The constant specimen mass for the ACP-series was attained after 14 days of water immersion, while the mass decrease due to long-term solubility in the BG-series lasted beyond 287 days. Calcium phosphates precipitated in composites with the BG filler loading of 10 wt% or more, as well as in all of the ACP-containing composites. The experimental composite series showed water sorption and solubility considerably higher than commercial materials
Epidemiology of hepatitis E in South-East Europe in the "One Health" concept
The significance of hepatitis E virus (HEV) as an important public health problem is rising. Until a decade ago, cases of HEV infection in Europe were mainly confined to returning travelers, but nowadays, hepatitis E represents an emerging zoonotic infection in many European countries. The aim of this manuscript is to perform a systematic review of the published literature on hepatitis E distribution in humans, animals and environmental samples ("One Health" concept) in the South-Eastern European countries. Comparison of the available data showed that the anti-HEV seroprevalence in the South-Eastern Europe varies greatly, depending on the population studied, geographical area and methods used. The IgG seroprevalence rates in different population groups were found to be 1.1%-24.5% in Croatia, up to 20.9% in Bulgaria, 5.9-%17.1% in Romania, 15% in Serbia, up to 9.7% in Greece and 2%-9.7% in Albania. Among possible risk factors, older age was the most significant predictor for HEV seropositivity in most studies. Higher seroprevalence rates were found in animals. HEV IgG antibodies in domestic pigs were detected in 20%-54.5%, 29.2%-50%, 38.94%-50% and 31.1%-91.7% in Serbia, Bulgaria, Romania and Croatia, respectively. In wild boars seroprevalence rates were up to 10.3%, 30.3% and 31.1% in Romania, Slovenia and Croatia, respectively. A high HEV RNA prevalence in wild boars in some countries (Croatia and Romania) indicated that wild boars may have a key role in the HEV epidemiology. There are very few data on HEV prevalence in environmental samples. HEV RNA was detected in 3.3% and 16.7% surface waters in Slovenia and Serbia, respectively. There is no evidence of HEV RNA in sewage systems in this region. The available data on genetic characterization show that human, animal and environmental HEV strains mainly belong to the genotype 3
Smjernice za prevenciju pneumokoknih bolesti cijepljenjem u bolesnika s kroničnom bubrežnom bolesti [Guidelines for the prevention of pneumococcal diseases by vaccination in patients with chronic renal disease]
Considering the reported cases of invasive pneumococcal disease in advanced chronic kidney disease
patients, in May 2017 the Steering Board of the Croatian Society of Nephrology, Dialysis and Transplantation
(CSNDT) of the Croatian Medical Association issued a decision on the preparation of Guidelines for the prevention
of pneumococcal diseases in patients with chronic kidney disease. The Guidelines are based on relevant medical
literature, Guidelines of the European Society of Clinical Microbiology and Infectious Diseases, the World Association
for Infectious Diseases and Immunological Disorders, and the Program for immunization, seroprophylaxis and
chemoprophylaxis for special population groups of the Croatian Institute of Public Health. Nephrologists, infectologists
and epidemiologists were involved in their development. There are two types of pneumococcal vaccine
available in Croatia that can be used for adults, conjugated vaccine PCV13 and polysaccharide vaccine PPSV23. The
Guidelines include planning and implementation of vaccination in chronic kidney disease patients who replace
kidney function with hemodialysis, peritoneal dialysis, renal transplant, or are candidates for treatment by
transplantation,
having one or more comorbidities: diabetes mellitus, chronic pulmonary disease, chronic cardiovascular
disease, chronic advanced liver disease, chronic kidney disease with solid or hematological tumors,
and splenectomy
Procjena vrijednosti testa skrivenoga objekta u ranoj dijagnostici Alzheimerove bolesti [Evaluation of the hidden goal test in early diagnosis of mild cognitive impairment and Alzheimer’s disease ]
Episodic memory impairment and spatial navigation deficit are often considered to be the
first symptoms of impairment due to neurodenerative changes in the structures of the medial
temporal lobeparticularly due to Alzheimer's disease (AD). As AD is a growing public health
issue, there is a great need for development of highly sensitive and specific tests or biomarkers
that would allow preclinical diagnosis of AD. This would also allow for a timely pharmaceutical
intervention.
Hidden Goal Test (HGT) has been developed and used for detection of spatial navigation
deficit in mild cognitive impairment (MCI) patients. Subjects were instructed to find an invisible
goal using its relation to the starting position and/or the orientation cues.
Between group differences in the average error measured in allocentric (allo), egocentric
(ego) and combined allocentric-egocentric (allo-ego) subtests were statistically significant for
MCI patients and healthy controls. There was significant difference in errors measured in allo,
ego and allo-ego HGT between MCI patients with MMSE values greater than or equal to 26
points and those below 26 points.
In conclusion, HGT proved to be a good screening tool, but also a good confirmatory
diagnostic test. Used in combination with other biomarkers, HGT can improve the early
identification of MCI patients who will convert to AD
A case report of severe recurrent varicella in an ankylosing spondylitis patient treated with adalimumab – a new side effect after 15 years of usage
BACKGROUND: Tumor necrosis factor-α (TNF-α) antagonists, most of which are monoclonal antibodies, became a widespread treatment for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis, psoriatic arthritis, hidradenitis suppurativa and uveitis. Their use is based on the blockage of TNF-α, which plays an important role in granulomas formation, development of phagosomes, activation and differentiation of macrophages, immune response against viral pathogens. The multiple adverse effects of TNF-α inhibition have been identified, including a two-to four-fold increased risk of active tuberculosis and other granulomatous conditions and an increased occurrence of some other serious bacterial, fungal and certain viral infections. -----
CASE PRESENTATION: A 34-year-old male patient with disseminated varicella and pneumonitis was admitted to our hospital. The diagnosis of varicella was established serologically by enzyme immunoassay (EIA) and by polymerase chain reaction confirmation of the virus in vesicular fluid. The patient has been receiving adalimumab and methotrexate for the last 3 years due to ankylosing spondylitis and was seropositive to varicella zoster virus prior to the introduction of TNF-α antagonists. Acyclovir was administered for 10 days with the resolution of clinical illness and radiological signs of pneumonitis.
CONCLUSION: Due to the use of biological agents, particularly TNF-α inhibitors, as a well-established therapy for some autoimmune diseases, new potential adverse events can be expected in the future and we wanted to point out one of them. To our knowledge this is the first case of recurrent disseminated varicella in a patient taking TNF-α antagonists