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Promjene u strukturi gena i izraženosti proteina DVL-1, DVL-2, DVL-3 te transkripcijskih faktora TCF-1 i LEF-1 u astrocitnim tumorima mozga [Changes in gene structure and protein expression of DVL-1, DVL-2, DVL-3 and transcription factors TCF-1 and LEF-1 in astrocytic brain tumors]
Get PDFAstrocytomas are the most common primary tumors of the central nervous system. According to the WHO classification, there are four grades of astrocytoma, considering their histology, molecular characteristics and prognosis, where the grade IV (glioblastoma) is the deadliest form and still without effective therapy. The aim of this dissertation was to investigate changes in gene structure and protein expression of Dishevelled family and transcription factors TCF1 and LEF1, the molecular components of the Wnt signaling pathway, in astrocytic brain tumors and compare results with clinical parameters. Four selected microsatellite markers for DVL1 (D1S468 and D1S243), DVL2 (D17S960) and DVL3 (D3S1262) genes have shown a significant number of samples demonstrating MSI and LOH, genetic changes that contribute to the genome instability in cancer. Diffuse astrocytomas (WHO grade II) analyzed with D1S468 (p=0.008) have shown the highest percentage of MSI (53.8%), while LOH was the most common in glioblastoma (31.2%) analysed with D3S1262 (p=0.007). The results obtained on the total sample indicate that the microsatellite instability is constantly present, with a more frequent appearance in lower grades and may be the cause of astrocytoma formation, whereas large deletions are significantly associated with the highest grade and have a role in progression. The levels of DVL1, DVL2 and DVL3 protein expression did not show statistically significant correlation with genetic changes. Nevertheless, statistically significant differences in the number of cells with certain level of expression of a single protein between the grades were observed. Bivariate correlation of all analyzed proteins showed a statistically significant positive correlation between DVL3 and TCF1 (p=0.020), DVL3 and LEF1 (p=0.006), TCF1 and LEF1 (p=0.021), while DVL1 and DVL3 were negatively correlated (p=0.002). DVL1 was also negatively correlated (p<0.001) with astrocytoma grade, while DVL3 (p<0.001), TCF1 (p=0.008) and LEF1 (p<0.001) showed positive correlation with malignancy grade suggesting involvement of these proteins in malignant progression. These results contribute to a better understanding of the molecular profile of astrocytic brain tumors and could serve as molecular markers of progression
Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia
Get PDFThe role of macroprolactinemia in women with hyperprolactinemia is currently controversial and can lead to clinical dilemmas, depending upon the origin of macroprolactin, the presence of hyperprolactinemic symptoms and monomeric prolactin (PRL) levels. Macroprolactinemia is mostly considered an extrapituitary phenomenon of mild and asymptomatic hyperprolactinemia associated with normal concentrations of monomeric PRL and a predominance of macroprolactin confined to the vascular system, which is biologically inactive. Patients can therefore be reassured that macroprolactinemia should be considered a benign clinical condition, resistant to antiprolactinemic drugs, and that no diagnostic investigations or prolonged follow-up should be necessary. However, a significant proportion of macroprolactinemic patients appears to suffer from hyperprolactinemia-related symptoms and radiological pituitary findings commonly associated with true hyperprolactinemia. The symptoms of hyperprolactinemia are correlated to the levels of monomeric PRL excess, which may be explained as coincidental, by dissociation of macroprolactin, or by physiological, pharmacological and pathological causes. The excess of monomeric PRL levels in such cases is of primarily importance and the diagnosis of macroprolactinemia is misleading or inadequate. However, macroprolactinemia of pituitary origin associated with radiological findings of pituitary adenomas may rarely occur with similar hyperprolactinemic manifestations, exclusively due to bioactivity of macroprolactin. Therefore, in such cases with hyperprolactinemic signs and pituitary findings, macroprolactinemia should be considered a pathological biochemical condition of hyperprolactinemia. Accordingly, individualized diagnostic investigations with the introduction of dopamine agonists, or other treatment with prolonged follow-up, should be mandatory. The review analyses the laboratory and clinical significance of macroprolactinemia in hyperprolactinemic women suggesting clinically useful diagnostic and treatment strategies
Lower choline-containing metabolites/creatine (Cr) rise and failure to sustain NAA/Cr levels in the dorsolateral prefrontal cortex are associated with depressive episode recurrence under maintenance therapy: a proton magnetic resonance spectroscopy retrospective cohort study
Get PDFBackground:
The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy. -----
Methods:
1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later. -----
Results:
Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio. -----
Conclusion:
Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode
Psychoneuroimmunological approach to gastrointestinal related pain
Get PDFBACKGROUND AND PURPOSE (AIMS):
Psychoneuroimmunology is both a theoretical and practical field of medicine in which human biology and psychology are considered an interconnected unity. Through such a framework it is possible to elucidate complex syndromes in gastrointestinal related pain, particularly chronic non-malignant. The aim is to provide insight into pathophysiological mechanisms and suggest treatment modalities according to a comprehensive paradigm. The article also presents novel findings that may guide clinicians to recognize new targets or scientists to find new research topics. -----
METHODS:
A literature search of 'PubMed' and 'Google Scholar' databases was performed. Search terms included: 'Visceral pain', 'Psychoneuroimmunology', 'Psychoneuroimmunology and pain', 'Pain in GI system', 'GI related pain', 'Pain and microbiota', 'Enteric nervous system', 'Enteric nervous system and inflammation', 'CNS and pain', 'Inflammation and pain in GI tract', 'Neurogastroenterology', 'Neuroendocrinology', 'Immune system in GI pain'. After searching and reading sources deemed recent and relevant, a narrative review was written with a tendency to discriminate the peripheral, intermediate, and central pathophysiological mechanisms or treatment targets. -----
RESULTS:
Recent evidence point out the importance of considering the brain-gut axis as the main connector of the central and peripheral phenomena encountered in patients suffering from chronic non-malignant gastrointestinal related pain. This axis is also a prime clinical target with multiple components to be addressed in order for therapy to be more effective. Patients suffering from inflammatory bowel disease or functional gastrointestinal disorders represent groups that could benefit most from the proposed approach. -----
CONCLUSIONS (BASED ON OUR FINDINGS):
Rather than proceeding with established allopathic single-target central or peripheral treatments, by non-invasively modulating the brain-gut axis components such as the psychological and neuroendocrinological status, microbiota, enteric nervous system, or immune cells (e.g. glial or mast cells), a favourable clinical outcome in various chronic gastrointestinal related pain syndromes may be achieved. Clinical tools are readily available in forms of psychotherapy, prebiotics, probiotics, nutritional advice, and off-label drugs. An example of the latter is low-dose naltrexone, a compound which opens the perspective of targeting glial cells to reduce neuroinflammation and ultimately pain. -----
IMPLICATIONS (OUR OPINION ON WHAT OUR FINDINGS MEAN):
Current findings from basic science provide sound mechanistic evidence and once entering clinical practice should yield more effective outcomes for patients. In addition to well-established pharmacotherapy comprised notably of anti-inflammatories, antibiotics, and proton-pump inhibitors, valid treatment strategies may contain other options. These disease modulating add-ons include probiotics, prebiotics, food supplements with anti-inflammatory properties, various forms of psychotherapy, and low-dose naltrexone as a glial modulator that attenuates neuroinflammation. Clearly, a broader and still under exploited set of evidence-based tools is available for clinical use
Clinical practice: evidence-based recommendations for the treatment of cervical dystonia with botulinum toxin
Get PDFCervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored
Vestibular evoked myogenic potentials and video head impulse test in patients with vertigo, dizziness and imbalance
Get PDFThe aim of this study was to compare vestibular evoked myogenic potentials (VEMP) and video head impulse test (vHIT) results in patients presenting with vertigo and dizziness. We retrospectively analyzed data of all patients with the chief complaint of vertigo, dizziness, or imbalance that underwent VEMP and vHIT from January 2015 to January 2016. A total of 117 patients (73 females, mean age 53.92±16.76) fulfilled inclusion criteria: group 1 included patients with the final diagnosis of vestibular neuritis (VN) (N=31 (16 right and 15 left VN)), group 2 included patients with the final diagnosis of vertigo of central origin (N=23) and group 3 included patients with the final diagnosis of unspecified dizziness (N=63). There was significant correlation between oVEMP asymmetry and asymmetry of the lateral canals 60ms gains on vHIT (r=0.225, p=0.026). Significant correlation between oVEMP and vHIT asymmetry was present in VN patients (r=0.749, p<0.001), while no correlation was found in the groups 2 and 3. oVEMP and vHIT lateral canals asymmetries were significantly greater in patients with vestibular neuritis. Furthermore, positive correlations of oVEMP amplitudes with 60ms gain of the lateral semicircular canal and slope of the anterior semicircular canal on vHIT, and cVEMP with slope of the posterior semicircular canal on the vHIT were found. These changes were significantly more pronounced in patients with vestibular neuritis. In conclusion, VEMPs and vHIT data should be used complementarily; asymmetry on both tests strongly supports peripheral vestibular system involvement
Bolesnici s povišenom koncentracijom kreatin kinaze u reumatološkoj ambulanti – prikaz skupine bolesnika [Patients with elevated creatine kinase levels in rheumatology outpatient clinic – case series]
Get PDFCreatine kinase (CK) is an enzyme found in different tissues and is responsible for the conversion of creatine into phosphocreatine. Muscle-derived CK has clinical significance as a marker of muscle injury. Elevated levels of CK are a frequent reason for referring the patient with suspected inflammatory idiopathic myopathies to the Rheumatology outpatient clinic. We analyzed the data from 23 referred patients collected over the period of two years. The analyzed data were collected from 16 female and 7 male patients aged 31 to 78 (with the average age of 53.43 years). Inflammatory idiopathic myopathies were confirmed in 13/23 (56.52%) patients (polymyositis in 76,92% and dermatomyositis in 23.08%). The treatment included nonpharmacological modalities and different immunosuppressive and/or immunomodulatory drugs (glucocorticoids, azathioprine, methotrexate, antimalarials and intravenous immunoglobulines)
Usporedba učinaka losartana i ramiprila u liječenju akutnoga infarkta srca s elevacijom ST spojnice [The comparison of the efficacy of ramipril and losartan in treatment of ST-elevation myocardial infarction]
Get PDFObjectives. The use of an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensinreceptor
antagonists (ARBs) reduces the incidence of heart failure and the risk of thrombosis
after acute ST-elevation myocardial infarction (STEMI) blockade of the renin-angiotensinaldosterone
system (RAAS).There are some differences between ACE-I and ARBs, as more
than 75% of angiotensin II in human myocardium originates from the alternative pathway
influenced only by ARB.
Goal. To compare the effect of 8-week and 6-month treatment of AMI patients with ramipril and
losartan on laboratory markers, echocardiographic parameters and clinical signs of heart
failure.
Patients and methods.108 patients who suffered an STEMI were randomized in a ramipril (55)
and a losartan (53) group, and followed-up for 8 weeks and 6 months. During treatment the
effect of drugs on clinical (Killip-Kimbal classes), laboratory markers (NT-pro BNP, PAI-1,
lipidogram) and echocardiographical parameters (EFLV, LVEDD) were compared.
Results. No statistically significant differences in the levels of laboratory markers,
echocardiographic parameters and clinical signs of heart failure were observed between the
ramipril and the losartan group, neither after 8-week nor after 6-month treatment.
Conclusions. After an uncomplicated STEMI, losartan was equally effective as ramipril in terms
of laboratory markers, echocardiographic parameters and clinical signs of heart failure
Croatian rotatory oblique three-dimensional osteotomy (CROTO) - a modified Wilson's osteotomy for adult hallux valgus intended to prevent dorsal displacement of the distal fragment and to reduce shortening of the first metatarsal bone
Get PDFAim: To evaluate biomechanical and clinical outcomes of a newly developed modification of the Wilson's osteotomy for hallux valgus: a three-dimensional subcaptial correction of the metatarsal head position with a simultaneous lateral and plantar shift with derotation intended to reduce displacement of the distal fragment and shortening of the first metatarsal bone. ----- Methods: Thirty four feet (28 female patients) underwent the new procedure and were evaluated before and 12 to 84 months (median=25.5) after the surgery. ----- Results: Plantar shift of the distal fragment was achieved in all feet. Shortening of the first metatarsal was moderate: ≤6 mm in 32/34 feet, 7 and 10 mm in the remaining two. Median difference in metatarsal index post- vs. pretreatment was -4.0. The hallux valgus angle, intermetatarsal and distal metatarsal articular angles were reduced in all feet. The American Orthopaedic Foot and Ankle Society score improved in all feet (median increase= 51.5). ----- Conclusion: The method allows for a lateral and plantar shift with derotation of the distal fragment and a mild/moderate shortening of the first metatarsal bone
Ekspresija Piwil2 i HMGA2 u papilarnom karcinomu štitnjače [Expression of piwil2 and HMGA2 in papillary thyroid carcinoma]
Get PDFDespite the extensive research, molecular markers for separating benign and
malignant neoplasms or identification of the subgroup of patients with papillary thyroid
carcinoma (PTC) and higher risk for more aggressive biological behaviour are yet to
be found.
The connection of Piwil2 and HMGA2 overexpression, either proteins or genes,
with more aggressive clinical course was identified in several malignant neoplasms.
Recent studies were focused on separating benign and malignant thyroid tumors. The
correlation between piwil2 and HMGA2 overexpression and clinical progression of PTC
has not been investgated.
The aim of this research was immunohistochemical analysis of piwil2 and
HMGA2 expression in PTC with and without regional lymph node metastasis (RLNM)
as well as in follicular adenomas (FA), hyperplastic nodules (HN) and non-neoplastic
thyroid tissue (NNTT).
By retrospective analysis of 150 tissue samples (30 PTC with RLNM and 30
PTC without RLNM, 30 FA, 30 HN, 30 NNTT) it was determined that expression of
piwil2 i HMGA2 was significantly higher in PTC (96,7%, 96,7%) as opposed to FA
(73,3%, 13,3%), HN (63,3%, 3,3%) and NNTT (76,7%, 0%), respecively, (P<0,001).
There was no statistically significant difference in expression of piwil2 and
HMGA2 between PTC with RLNM and PTC without RLNM (100,0% vs 96,7%; 93,0%
vs 96,7%, respectively). Overexpression of piwil2 and HMGA2 can not be associated
with more aggressive biological behaviour of PTC.
HMGA2 overexpression predicts PTC with high sensitiyity (97,78%) and
specificity (100%)