Papers by Ninoslav Mimica
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Dosadašnja istraživanja koncentracija elemenata u tragovima u kosi i ostalim
biološkim matricama ... more Dosadašnja istraživanja koncentracija elemenata u tragovima u kosi i ostalim
biološkim matricama kod osoba sa shizofrenijom davala su kontradiktorne rezultate.
Mogući uzrok tome vjerojatno su nedovoljno osjetljivi analitički postupci i različite
metode mjerenja koje su upotrebljavane u istraživanjima.
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Collegium Anthropologicum , 2011
The aim of this study is to determine the word frequency for all thirty letters of the Croatian a... more The aim of this study is to determine the word frequency for all thirty letters of the Croatian alphabet and to collect normative data for the letter fluency task in Croatian speakers. Ninety two healthy participants were given each of the Croatian letters, and asked to generate as many words as possible in 60 seconds for each letter Results suggested that participants generated most frequently words starting with the letters as follows: "K", "P", "S" and "M".
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Demencija je sindrom globalnog i progresivnog oštećenja stečenih kognitivnih sposobnosti pri očuv... more Demencija je sindrom globalnog i progresivnog oštećenja stečenih kognitivnih sposobnosti pri očuvanoj svijesti prouzročen organskom bolešću središnjeg živčanog sustava u kojem su posebno oštećene sposobnosti pamćenja, učenja, apstraktnog mišljenja, orijentacije te poimanja vidno‐prostornih odnosa. Prevalencija i incidencija Alzheimerove bolesti (AB), najčešćeg uzroka demencije, znatno je veća kod žena nego kod muškaraca, a ta se razlika s dobi povećava. Dvostruko veća učestalost AB kod žena u odnosu na muškarce djelomično se može objasniti time što žene imaju očekivano dulji životni vijek. Žene imaju lošiju kognitivnu izvedbu na mnogim neuropsihologijskim testovima u odnosu na muškarce u istom stadiju bolesti, odnosno višestruke kognitivne funkcije kod žena teže su i šire zahvaćene nego kod muškaraca. Mogući razlozi za ovakvu nepovoljnost naspram žena su redukcija estrogena u postmenopauzi, veće kognitivne rezerve muškaraca te utjecaj apolipoproteina E. Određeni biološki čimbenici također bi mogli objasniti različite kliničke manifestacije AB s obzirom na spol. Osim što prema prezentiranim podatcima žene češće obolijevaju od AB, žene su također te koje u bitno većoj mjeri pružaju neformalnu njegu ljudima s demencijom, te su oko dvije trećine neformalnih njegovatelja žene. Zaključno, u daljnjem istraživačkom i kliničkom radu s AB svakako bi trebalo obratiti pozornost na spoznaje o spolnim razlikama u razvoju i progresiji ove bolesti. / Dementia is a syndrome of global and progressive impairment of acquired cognitive abilities with preserved consciousness caused by an organic illness of the central nervous system with especially pronounced damage to the ability to memorise, learn, think abstractly, orientate, and perceive spatial relations. The prevalence and incidence of Alzheimer's Disease (AD), the most common cause of dementia, is considerably greater in women than in men, and that difference increases with age. The fact that AD occurs twice as often in women than in men may be partially explained by a longer life expectancy among women. Women show worse cognitive performance on numerous neuropsychological tests in comparison to men during the same stage of the disease, meaning that multiple cognitive functions are more widely and severely impaired in women than in men. Possible reasons for such unfavourable results among women are a reduction of oestrogen during post-menopause, larger cognitive reserves in men, and the influence of apolipoprotein E. Certain biological factors may also explain various clinical manifestations of AD regarding sex. Apart from the fact that, according to presented data, women develop AD more often than men, women are also those who offer informal care to people with dementia in much greater numbers, and almost two thirds of informal caregivers are women. In conclusion, further research and clinical work with AD should certainly pay attention to insights about sex differences in the development and progression of this disease. Soc. psihijat. | 46 (2018) | 58-76 PREGLED / REVIEW
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Sažetak. Cilj rada je opisati primjenu psihometrijskih i kliničkih instrumenata za procjenu postt... more Sažetak. Cilj rada je opisati primjenu psihometrijskih i kliničkih instrumenata za procjenu posttraumatskog stresnog poremećaja (PTSP-a) i ocjenu terapijskog učinka. Uz dijagnostičke kriterije za PTSP, pomoć u dijagnostici PTSP-a predstavlja i uporaba psihometrijski validiranih instrumenata. Instrumenti za procjenu PTSP-a obično se dijele u dvije skupine: prvu skupinu čine strukturirani i polustrukturirani intervjui koji zahtijevaju individualan pristup i specifične vještine i znanja iskusnog kliničara koji ih primjenjuje. Drugu skupinu instrumenata čine psihometrijske ljestvice koje omogućuju procjenu intenziteta simptoma. Ljestvice za mjerenje PTSP-a daju informacije o vrsti i intenzitetu simptoma. Također, mnoge od njih postavljaju granične vrijednosti koje služe kao indikator prisutnosti ili odsustva poremećaja. Izbor instrumentarija ovisi o cilju istraživanja, teorijskom kontekstu i raspoloživom uzorku. Složenost procesa procjene, odnosno izbor instrumenata koji će se primijeniti, u velikoj mjeri ovisi o kontekstu unutar kojeg se procjena vrši. Precizna dijagnostička procjena uključuje integraciju podataka dobivenih iz dvaju temeljnih područja: prvo područje je ispitivanje izloženosti traumi, a drugo je procjena simptomatike PTSP-a. Ovdje valja naglasiti da je prije primjene strukturiranih kliničkih intervjua i ljestvica procjene nužno provesti obuku i trening ocjenjivača te objektivno izmjeriti podudarnost njihovih procjena na svakoj od čestica pojedine ljestvice. Za mjerenje simptoma PTSP-a konstruiran je i velik niz samoocjenskih ljestvica. Za ocjenu terapijskog učinka također se koriste različiti tipovi instrumenata, odnosno, i strukturirani intervjui i samoocjenske ljestvice. Može se naglasiti da je upotreba psihometrijskih instru me-nata važna u metodologiji suvremenog kliničkog stručno-znanstvenog rada u procjeni PTSP-a i praćenju terapijskog učinka. U tu svrhu potrebno je ove instrumente i nadalje razvijati. Abstract. The aim of this article is to describe the application of psychometric and clinical instruments for the assessment of posttraumatic stress disorder (PTSD) and the evaluation of the treatment effect. Beside diagnostic criteria for PTSD, the use of valid psychometric instruments helps in PTSD diagnostics. Instruments for the assessment of PTSD are usually divided into two groups: the first group consists of structured and semi structured interviews that require individual approach and specific skills and knowledge of an experienced clinician who applies them. The second group of instruments consists of psychometric scales which enable the assessment of symptom intensity. The scales for measuring PTSD reveal information about the type and intensity of symptoms. Also, many of them set threshold values that indicate the presence or absence of a disorder. The choice of instruments depends on the aim of research, theoretical context and available sample. The complexity of the assessment process and the choice of instruments that will be applied, depends greatly on the context within which the assessment is made. An accurate diagnostic assessment includes the integration of data acquired from two basic fields: the first field is examination of exposure to trauma and the second is assessment of symptoms of PTSD. It is important to emphasize that it is necessary to exercise instruction and training of evaluators and objectively measure congruence of their assessments for every item of particular scale. A large number of self
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A B S T R A C T The principles and practice of assessing the human body nutritional status or its... more A B S T R A C T The principles and practice of assessing the human body nutritional status or its environmental exposure through hair bioelement analysis are presented; herein the term " bioelements " is used as a common denominator for the major elements, trace elements and ultra-trace elements that are found in the human body. The accumulation of bioelements in the hair followed the statistical Power Law and the resulting sigmoid curve can be zoned into five regions in the ascending order of abundance (Low, Marginal, Adequate, High, and Excessive). The Adequate linear region of the bioassay sigmoid curve may be further subdivided into Low adequate, Recommended, and Ample adequate sub regions in a 60:30:10 ratio. Phosphorus was the most invariant bioelement since its hair concentration varies minimally regardless of the geographical place of living, the twenty years' time interval between the analyses, sex, race and instrumentation, i.e., atomic absorption spectrometry (AAS) atomic emission spectrometry (AES), and inductively plasma mass spectrometry (ICP MS). The osteotrophic (bone seeking) bioelements: Ca, Mg, and Sr, were 2.5 times more abundant in the hair of women than men. Two principal electrolytes of the body (Na, K) of the multi-bioelement hair profile were markedly increased in the depressed subjects diagnosed according to the American Psychiatric Association MSD-IV classification criteria. This increase in the hair Na and K of the depressed subjects was also associated with the decrease of vasopressin in the peripheral blood. The factor analysis revealed strong association of depression with sex (women > men in a 2.5:1 ratio), and with the metals from the Nieboer-Richardson series which form strong covalent bonds with proteins. We propose that the biological roots of depression are related to the non-specific impairment of the intracellular osmotic balance and ionic gradient due to the Na + K + ATPase failure from whatever cause acting either separately or in combination. We also put forward the idea of how children's autism may be related to a disproportional growth rate of various organs and tissues if children are fed up to their maximal genetic growth capacity. Finally, we have suggested the hypothesis on how the syntax or integration of the internal metabolic wiring of the bioelements in the body may occur. We have suggested the hypothetical existence of two complex distinct five-bioelement " rotors " , the P-rotor and the N-rotor, where the P-rotor integrates the mileau interior (Na, K) ions with the perception/excitability (Mg, Ca) ions. Thus, the complex five element interdependence is cross related to P which provides the energy from the phosphorus of the DNA nucleotide backbone. The hair multi-bioelement profile analysis allows us to envisage the more complex structural metabolic features that bioele-ments are playing in our bodies.
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Full Text References Catechol-O-Methyltransferase (COMT) is an enzyme that degrades catecholamine... more Full Text References Catechol-O-Methyltransferase (COMT) is an enzyme that degrades catecholamines including dopamine. COMT rs4680 and rs4818 polymorphisms affect COMT activity and therefore brain dopamine levels and function. The G variants of both COMT rs4680 Val158Met (G>A substitution) and rs4818 (C>G substitution) polymorphisms are associated with greater COMT activity and lower prefrontal dopamine levels (,). Altered hypothalamic pituitary-adrenal (HPA) axis is the main feature of schizophrenia (). In schizophrenic patients, morning salivary cortisol was not significantly associated with smoking, symptoms of schizophrenia or antipsychotic medication, but it was affected by diurnal rhythm (). COMT polymorphisms might alter the HPA axis function and cortisol secretion through catecholaminergic (dopaminergic and noradrenergic) pathways (). Interactions between stress and COMT polymorphisms in schizophrenia-spectrum phenotypes were reported (). However, the data regarding association between COMT genotypes or haplotypes and cortisol in adult schizophrenic patients are missing. The hypothesis of this study was that COMT rs4680 and rs4818 polymorphisms are associated with salivary cortisol levels in adult patients with schizophrenia. This study included 190 adult Caucasian patients (65 males, 125 females) with schizophrenia, 51.3 ± 26.7 years old, diagnosed using Structured Clinical Interview for DSM-IV, with total Positive and Negative Syndrome Scale (PANSS) scores of 73.57 ± 12.92 (mean ± SD). Patients were recruited from the Psychiatric Hospital Vrapce,
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SUMMARY Introduction: The aim was to report the occurrence of after application of olanzapine lon... more SUMMARY Introduction: The aim was to report the occurrence of after application of olanzapine long-acting injection (OLAI) in patients with schizophrenia during one year period. Subjects and methods: During one year period, OLAI was applied to 30 patients with schizophrenia (18 men, 12 women) who were non-adherent to previous treatment with oral olanzapine. Patients were 20-58 years of age (39 years old on average), diagnosed with SCID based on DSM-IV-TR criteria. Patients received OLAI in dosage between 210-405 mg (287±62 (mean ± SD)) every 2-4 weeks. Results: Out of 30 patients that received OLAI, 29 patients improved significantly without side-effects, and one patient developed post-injection delirium/sedation syndrome (PDSS). The patient's somatic condition stabilized and treatment with OLAI was discontinued due to the PDSS. Conclusion: The occurrence of PDSS is not common and when it occurs, in our experience, it was reversible.
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The more frequently encountered ophthalmologic adverse events of neuropsychiatric agents include ... more The more frequently encountered ophthalmologic adverse events of neuropsychiatric agents include thioridazine-induced retinopathy, tricyclic antidepressant-induced accommodation interference and glaucoma, and lithium carbonate-induced exophthalmos and papilloedema. Clozapine may produce blurred vision, but this side effect is usually time-limited (1). According to available evidence, episodes of transient visual disturbances appear during treatment with risperidone but disappear when medication with risperidone is reduced to a lower daily dosage (2,3). Methods We assessed clinical somatic state, using laboratory values, ophtalmoscopy, biomicroscopy, EEG, and brain magnetic resonance imaging (MRI). We assessed psychic profiles, using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Clinical Global Impressions (CGI). We assessed side effects, using the Simpson–Angus Rating Scale for Extrapyramidal Syndrome, the Barnes Akathisia Scale (BAS), and the Extrapyramidal Symptom Rating Scale (ESRS). Case Report In June 2002, because of psychotic symptoms, the patient (aged 36 years, single, with no children, and an economist) was hospitalized in our clinic with a discharge diagnosis of psychosis schizoaffectiva according to DSM-IV (4). After admission to our clinic, we continued therapy with promazine 400 mg daily, along with alprazolam 0.75 mg daily, zolpidem 10 mg daily, and fluoxetine 20 mg daily, and we started therapy with risperidone 2 mg daily. At baseline visit (that is, the first day of therapy with risperidone), we performed the PANSS, CGI, Simpson–Angus Rating Scale for Extrapyramidal Syndrome, BAS, and ESRS. The patient's total PANSS score was 86, and the CGI score was markedly ill. The values of hematology, biochemistry, and urinalysis were in referent range. EEG was normal. Because of persisting positive symptoms, we increased the dosage of risperidone to 12 mg daily. Promazine was discontinued from therapy. The patient became fully remitted after 4 weeks and was discharged. After 6 weeks of risperidone therapy (4 weeks as an inpatient and 2 weeks as an outpatient), the patient reported blurred vision. To clarify the origin of blurred vision, we assessed clinical somatic state. The values of hematology, biochemistry, and urinalysis were in referent range. The results of the neuropsychological assessment excluded lesions caused by cranial trauma, diffuse brain damage, or lesions caused with slow progressive process. The patient's brain MRI was normal, and the biomicroscopy results revealed no abnormalities. Ophtalmoscopy showed no pigment mottling or disturbances in the macular regions. Subsequently, the dosage of risperidone was reduced to 4 mg daily, and 2 weeks later, the patient reported full recovery of vision without worsening her mental condition. The diagnostic procedure showed no organic cause of the blurred vision. Also, blurred vision was not related to concomitant therapy. Conclusion Blurred vision is a side effect associated with treatment with risperidone in higher dosages, which may disappear, without worsening of symptoms, after decreasing the daily dosage of risperidone. Further observation is necessary for more precise understanding of these conditions, which is essential for diagnosis and appropriate treatment.
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OBJECTIVES: The primary objective of this clinical trial was to assess the clinical activity of v... more OBJECTIVES: The primary objective of this clinical trial was to assess the clinical activity of various doses and formulations of AFFITOPE® AD02 following its repeated s.c. administration to patients with early Alzheimer´s disease (AD), based on the evaluation of cognitive and functional domains. DESIGN: It was designed as a randomized, placebo-controlled, parallel group, double blind, multicenter phase II trial with 10 regular outpatient visits and 6 telephone interviews. SETTING: The trial was performed at 32 sites in six countries. PARTICIPANTS: A total of 332 patients were enrolled and 265 patients completed the trial in 3 treatment groups with AD02 and 2 control groups with aluminum oxihydroxide, here named IMM-AD04. Patients were randomly assigned to 5 groups: two doses of IMM-AD04, 25µg AD02 (in two different formulations) and 75µg AD02. INTERVENTION: At months 0, 1, 2, 3, 9 and 15, each patient received a single s.c. injection of the corresponding preparations of AFFITOPE® AD02 or the control, IMM-AD04. MEASUREMENTS: Co-primary efficacy outcomes included a measure of cognition (adapted AD Assessment Scale cognitive [aADAS cog]), and a measure of function (adapted AD Cooperative Trial Activities of Daily Living [aADCS-ADL]). A primary composite score was the sum of these two scores. RESULTS: Treatments were generally well tolerated and adverse events (AEs) were seen at similar rates across all treatment groups, with the exception that more injection site reactions were seen in the groups with a higher level of adjuvant. None of the AD02 groups showed a benefit over the IMM-AD04 controls for primary or exploratory efficacy outcomes. The control groups differed on aADCS-ADL and therefore couldn't be pooled (p=0.039). Unexpectedly, the 2mg IMM-AD04 showed statistically significant effects over the other groups on several clinical outcomes including: aADAS-cog, aADL, Composite, ADAS-cog, CDR-sb, and QOL-AD Caregiver as well as two biomarker outcomes: right and total hippocampal volume (all p<0.05). 48% of patients in the IMM-AD04 2mg group had no decline in the composite outcome over 18 months compared to 17%-31% in the other groups, which is consistent with historical placebo groups. CONCLUSION: No significant treatment effects were seen for the investigational compound AD02. However, the IMM-AD04 2mg group showed statistically significant effects over all other groups on several clinical outcomes as well as a slowing of decline on right hippocampal volume. The data support further development of IMM-AD04 as a disease modifying agent in line with EMA/FDA definitions.
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A B S T R A C T Boron is a non-essential ubiquitous trace element in the human body. The aim of t... more A B S T R A C T Boron is a non-essential ubiquitous trace element in the human body. The aim of this study was to assess boron nutritional status by analyzing boron frequency distribution in the long-term biological indicator tissue of hair and the short-term biological indicator of whole blood. Hair samples were analyzed in 727 apparently healthy subjects (263 ♂ and 464 ♀) and the whole blood boron was analyzed in the random subsample of them (80 ♂ and 152 ♀). Samples were analyzed by the ICP-MS at the Center for Biotic Medicine, Moscow, Russia. The adequate reference range for hair boron concentration was (μg • g −1) 0.771-6.510 for men and distinctly lower 0.472–3.89 for women; there was no detectable difference in the whole blood boron for the adequate reference range between men (0.020–.078) and women (0019–0.062). Boron may play an essential role in the metabolism of the connective tissue of the biological bone matrix.
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Memantine is approved for treatment of moderate to severe Alzheimer disease (AD) but is also inve... more Memantine is approved for treatment of moderate to severe Alzheimer disease (AD) but is also investigated as a treatment option for a number of different conditions, and even though there are reports of a number of adverse effects, including new-onset seizures and psychosis, it is considered to be generally well tolerated. We report two cases of repeated loss of consciousness after long-term memantine treatment in patients with AD, which resolved after its discontinuation. The possible changes in the central nervous system after prolonged memantine use for AD are briefly discussed, as well as its capacity to facilitate and/or change the expression of seizure activities. Presented cases indicate the need for increased caution and careful weighing of benefits and risks of prolonged treatment with memantine in patients with AD, as well as for careful evaluation of risks of combining memantine with other medications.
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Keywords: Alzheimer's disease Brain derived neurotrophic factor Val66Met Male and female subjects... more Keywords: Alzheimer's disease Brain derived neurotrophic factor Val66Met Male and female subjects Onset of disease Psychotic symptoms Objective: Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder with a high prevalence. Since behavioral disturbances, such as psychotic symptoms, represent a key feature of AD, genes related to dopamine, serotonin and brain derived neurotrophic factor (BDNF), are considered as candidate genes for AD. BDNF is a neurotrophin that regulates neurodevelopment, neuroplasticity, and neuronal functions. BDNF is involved in the etiopathogenesis of psychiatric and neurodegenerative disorders. A single base pair polymorphism (BDNF Val66Met) was reported to be associated with AD and/or schizophrenia, as well as other psychoses, although some studies failed to replicate these findings. The aim of the study was to evaluate the association between BDNF Val66Met variants and AD, as well as onset of AD or presence of psychotic symptoms in AD. Method: BDNF Val66Met was analyzed in 211 patients with AD and in 402 aged healthy control subjects. All subjects were ethnically homogenous Caucasians from Croatia, and were subdivided according to the gender, onset of AD, and presence of psychotic symptoms. A χ 2 test, with Bonferroni correction and standardized residuals were used to evaluate the data. Results: Distribution of the BDNF Val66Met genotypes differed significantly between male and female AD patients with or without psychotic symptoms. This difference was due to the significant contribution of the Met/Val genotype and the combined Met/Met and Met/Val genotypes between psychotic and non-psychotic symptoms in male, but not in female patients with AD. The frequency of the gene variants of the BDNF Val66Met did not differ significantly among male and female patients with AD and control subjects, or between male and female patients with early or late onset AD. There were significant sex related differences in age, duration of illness and scores of dementia between patients with AD. Conclusion: Our male patients were younger, had shorter duration of illness, and had less severe dementia and higher cognitive performance than female AD patients. The gene variants of the BDNF Val66Met polymorphism were significantly associated with the presence of psychotic symptoms in male, but not in female patients with AD. The results had adequate statistical power to suggest that BDNF Val66Met was not related to susceptibility to AD or the onset of AD, but that presence of one or two Met alleles of BDNF Val66Met polymorphism might present a risk factor for psychosis in AD.
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Ai m : The ai m of this study was standardization and validation of the Mini-Mental State Examina... more Ai m : The ai m of this study was standardization and validation of the Mini-Mental State Examination (MMSE) in the general Croatian aging population. Methods: Three-hundred and forty-four participants underwent the MMSE test, 217 cogni-tively healthy subjects without neurological and psychiatric disorders and 127 patients with mild cognitive impairment (MCI) or dementia. Results: The optimal cutoff point for screening of the general Croatian population (cognitively healthy vs. MCI and dementia) is 26/27; in the Croatian population aged ≥65 years, the cutoff point is 24/25, whereas for screening of highly educated persons (≥14 years of education) aged ≥65 years a higher cutoff point should be used (26/27). Conclusions: MMSE results when standardized and validated in a certain population might better contribute to recognition of the individuals at risk that should be directed to dementia outpatient clinics.
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SUMMARY The aim of this review is to describe side effects of five antidementives which are appro... more SUMMARY The aim of this review is to describe side effects of five antidementives which are approved by the United States Food and Drug Administration (FDA); four acetylcholinesterase inhibitors and one glutamate-or N–metyl-D–aspartat receptor antagonist-memantine. The antidementives are well tolerated and undesired effects are rare; except hepatotoxicity of tacrine and gastrointestinal side effects of donepezil, rivastigmine, galantamin and tacrine that result from acetylcholinesterase inhibition. Nausea, diarrhea, vomiting, and weight loss are the most common side effects of the acetylcholinesterase inhibitors. Significant cholinergic side effects can occur in patients receiving higher doses; often they are related to the rate of initial titration of medication. Memantine is the first noncholinesterase inhibitor indicated for Alzheimer's disease. The side effects which may occur during the treatment with memantine are constipation, dizziness, headache and confusion. These effects if appears are mild end transient.
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Papers by Ninoslav Mimica
biološkim matricama kod osoba sa shizofrenijom davala su kontradiktorne rezultate.
Mogući uzrok tome vjerojatno su nedovoljno osjetljivi analitički postupci i različite
metode mjerenja koje su upotrebljavane u istraživanjima.
biološkim matricama kod osoba sa shizofrenijom davala su kontradiktorne rezultate.
Mogući uzrok tome vjerojatno su nedovoljno osjetljivi analitički postupci i različite
metode mjerenja koje su upotrebljavane u istraživanjima.