Hemispheric infiltrative grade II gliomas in adults: association of residual tumour volume and extent of tumour resection with malignant transformation.

OBJECTIVES: Evaluation of the impact of surgical treatment on malignant transformation (MT) of adult supratentorial infiltrative grade II gliomas (G2G) in a series of chemotherapy and radiotherapy-naïve patients. BACKGROUND: Despite G2G are slow-growing tumours, they typically undergo MT with a subsequent fatal disease course. An extensive resection alone likely changes their biological behaviour and defers MT; however, this impact is not unequivocally confirmed. METHODS: Thirty-eight chemotherapy and radiotherapy-naïve adult patients operated from 2005 till 2014 for a G2G were investigated. Based on postoperative magnetic resonance imaging (MRI) and/or positron emission tomography follow-up (FU) scans, the patients were classified as "transformers" (15 patients in whom MT occurred during the FU-period) and "non-transformers" (23 patients). RESULTS: The follow-up period of "non-transformers" was longer (p <0.0001). After adjustment for known risk factors - age, male sex, astrocytoma histology, preoperative tumour volume, preoperative contrast enhancement and positive isocitrate dehydrogenase 1 gene mutation status - a larger log postoperative tumour volume (p=0.031) and a smaller extent of resection (p=0.0086) were associated with a shorter MT-free survival. CONCLUSION: In our series, less extensive resections were associated with a shorter time to MT. Our data support an adoption of techniques enabling extensive G2G resections, such as intraoperative imaging and awake resections, into everyday routine (Tab. 1, Fig. 2, Ref. 40).

Magnetic resonance spectroscopy - its added value in brain glioma multiparametric assessment.

OBJECTIVE: In this study, we analysed the results of magnetic resonance spectroscopy (MRS) in the patients with gliomas, including the error rate, MRS parameters variability, correlations with gene mutations and overall usefulness for clinical practice. MATERIAL AND METHODS: Eighty patients with glial tumours were examined by multiparametric MRI completed with single voxel MRS, as one group, then as two separate groups according to progression of the disease after the initial surgery. The error rate between the groups, MRS parameters variability, hazard ratios and correlations between metabolites, genetic markers and tumour grade were all analysed. RESULTS: Variability in Cho/Cr(h) was significantly higher in the group with a disease progression (p = 0.044). In the patients with a stable disease, strong significant negative correlations between Cho/Cr and Cho/NAA with p53 mutation (-0.945 and -0.812 respectively, p < 0.05) and between Cho/Cr and IDH1, 2 mutation (-0.796, p < 0.05) were found. In the patients with tumour progression, a significant positive correlation of NAA/Cr with 1p19q codeletion (0.486, p < 0.05) and of Cho/Cr and Cho/NAA values with p53 mutation (0.477 and 0.416, p < 0.05) were identified. Tumour grade positively correlated with Cho/Cr values (0.304, p = 0.02) in the whole patient group. CONCLUSION: MRS brings an added value to multiparametric MRI evaluation of brain tumours in the patient follow-up after an initial surgery, especially in ambiguous findings (Tab. 5, Fig. 2, Ref. 29).

Bilateral testicular germ cell tumors - 50 years experience.

OBJECTIVE: This study analysed the characteristics and outcome of the patients with bilateral germ testicular cell cancer (TC), especially synchronous. METHODS: Among 2.124 TC patients diagnosed between 1970 and 2020, 96 (4. 5%) developed the 2nd TC. Nine occurred synchronously and 87 were metachronous. Patients were analysed according to the age and histological type of bilateral TC in comparison with unilateral TC. RESULTS: The mean follow-up of all 2,124 patients was 14.9 years. Unilateral TC occurred in 2.028 patients (the mean age of 32.4 years), 707 of them had seminoma, 1.310 nonseminomatous (NS) TC and 11 spermatocytic tumours. The 1st tumour of metachronous bilateral disease was diagnosed at a significantly younger age (27.1 years) compared to the unilateral disease (32.4 years). The mean interval between the 1st and the 2nd TC was 8.2 years. Patients with NSTC had a longer mean interval (9.2 years) between the 1st and the 2nd TC in comparison with seminoma patients (6.7 years). The mean age at diagnosis for seminoma was significantly higher (31.3 years) compared to the NSTC (24.1 years). Bilateral seminoma occurred in 5 synchronous bilateral TC patients, four patients had discordant histology, none presented with bilateral NSTC. CONCLUSIONS: Bilateral TC is a rare and requires individualized management of patients (Tab. 5, Fig. 4, Ref. 32).

RADIATION MACULOPATHY AFTER ONE-DAY SESSION STEREOTACTIC RADIOSURGERY IN PATIENTS WITH CILIARY BODY AND CHOROIDAL MELANOMA.

INTRODUCTION: Nowadays radiotherapy is the standard treatment care for patients with uveal melanoma. In Slovakia the only one option is a one-day session stereotactic radiosurgery at linear accelerator LINAC. Irradiation of surrounding tissues of the eye and orbit causes radiation complications. One of the most serious and vision-threatening is the radiation retinopathy, which divides into maculopathy and peripheric retinopathy. The clinical signs include microanerysms, teleangiectases, hard exsudates, cotton wool spots and macular edema, neovascularisation, and vitreous hemorrhage. Radiation macular edema can be classified by optical coherence tomography into cystoid or noncystoid edema. On fluorescein angiography macular edema is divided into non-ischemic and ischemic, while the latter means usually irreversible loss of the visual acuity. This paper is focused on risk factors of radiation retinopathy although it strongly influences functional result of radiotherapy and preservation of the visual acuity. PURPOSE: By means of bivariate and multivariate analysis to determine the association of radiation dose and other variables with the development of radiation maculopathy. MATERIAL AND METHODS: The retrospective analysis of 168 patients with ciliary body or choroidal melanoma who performed one-day session stereotactic radiosurgery on a linear accelerator LINAC in a period 2007-2016. RESULTS: The prevalence of the radiation maculopathy was 29% with the median time from the irradiation to maculopathy 16 months. Median radiation dose on the macula was 37 Gy. Variables statistically significantly associated with the maculopathy were: radiation dose (p = 0.0016), postequatorial location of the tumor (p = 0.0271) and better visual acuity before treatment (p = 0.0007). The tumor touch of the macula was strongly associated with the visual acuity in the bivariate analysis (p = 0.0006), thus it could be omitted from the final model. DISCUSSION: The radiation dose on a macula is the key determinant for radiation-induced maculopathy, according to other authors and our study approvingly. Other variables were related to proximity of the tumor to the macula, so the radiation dose on the macula was higher indirectly. Better visual acuity before treatment as a risk factor for maculopathy can be a consequence of: a) earlier diagnostics of tumor with proximity to the posterior pole, b) lower enucleation rate; frequency of the enucleation was 1.6 higher in patients without maculopathy. Naturally, on enucleated eyes maculopathy was not diagnosed. Five patients underwent intravitreal application of the bevacizumab as a treatment of the radiation maculopathy, without improvement of the visual acuity. CONCLUSION: Radiation complications can be vision and eye threatening. Radiation maculopathy is a consequence of higher radiation dose on the macula. The treatment modalities of radiation maculopathy are rather ineffective.

Recurrence after sentinel lymph node biopsy in cutaneous melanoma: a single-center experience in Slovak patients.

The standard approach in the management of cutaneous malignant melanoma is considered to be a complete excision of the primary lesion with an appropriate margin of the normal tissue according to Breslow thickness. Usually sentinel lymph node biopsy (SLNB) can help to determine the nodal status, and thus improve the accuracy of staging of the disease. However, the role of SLNB in melanoma treatment remains controversial. NCCN guidelines strongly support routine performance of therapeutic lymphadenectomy in all melanoma patients with clinically positive nodes without radiographic evidence of distant metastases. Patients with positive SLNB should have had completion lymph node dissection (CLND) for regional disease control. Between 2012 and 2016, 168 consecutive patients underwent surgery for primary cutaneous malignant melanoma at St. Elisabeth Cancer Institute in Bratislava. The indication for SLNB and the procedure was made according to international guidelines. In this retrospective study, a cohort of 78 patients was analyzed (35 women and 43 men). Inclusion criteria comprised patients with cutaneous melanoma with no evidence of distant metastases or clinical lymphadenopathy. SLNB comprised a dual labelling method (Tc-99m Nanocolloid / blue dye) in a one-day protocol. Median follow-up was 657 days. The primary composite outcome was the time to the first disease-related event (death, reintervention, worsening of symptoms). Primary outcome measures were overall (disease-specific) and disease-free survival. The overall identification rate of SLN in melanoma patients by dual labelling method was 98.5%. All patients with positive SLNB on frozen section underwent complete regional lymphadenectomy. Using multivariable analysis Breslow thickness of the lesion (p=0.00004, HR 4.03 on logarithmic scale) was identified as the strongest independent predictor of the disease-free survival (DFS) and male gender was significant predictor of DFS. An increase in tumor thickness was associated with significantly higher risk of an event. Neither SLN positivity nor initial S-100 level proved to be significant predictors of the event at the 0.05 level of probability. Multidisciplinary approach represents the gold standard of care for melanoma patients and surgery remains the best option for most localized cases. Although the usefulness of SLNB procedure has been questioned, it provides an excellent staging method, moreover, it can identify high-risk patients. The routine use of completion lymphadenectomy after a positive SLNB is still controversial. It is not clear whether CLND following a positive SLN biopsy improves survival but it could provide regional disease control.

Idiopathic Granulomatous Mastitis - a new approach in diagnostics and treatment.

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking carcinoma and puerperal or non-puerperal mastitis. The primary purpose of this prospectively performed case control study was to compare clinical and imaging signs of IGM with the reference group of nonspecific, non- puerperal mastitis (NM) to identify the most typical clinical and imaging signs essential for a correct differential diagnosis. The secondary purpose was to present a new approach to non-invasive treatment. Thirty-nine women with histologically proven IGM and twenty-six patients with nonspecific mastitis underwent clinical examination, breast ultrasound (US), mammography (MG) and MRI examination. The most typical signs were selected for each group, and method and were statistically evaluated. The effectivity of colchicine, vitamin E and ribwort plantain tincture in treatment was assessed by clinical examination and imaging. Typical clinical signs of IGM included unilateral acute onset of breast edema, redness, palpable masses, missing fever, lymphadenopathy, no response to antibiotics or surgical interventions. Ultrasound revealed: "finger-like" structures (100%), ductectasias (76.9%), abscesses (76.9%), and lymphadenopathy (15.4%), while in MRI skin and tissue edema (100%), multicentric lesions (100%), abscesses (76.9%), ring enhancement (84.6%), lymphadenopathy (15.4%) and small enhancing lymph nodes (38.5%) were observed. Among the clinical signs, fistulas, hypoechoic mass, ductectasias and diffusion weighted images (DWI) restriction were significantly more frequent in patients with IGM than in those with NM. Treatment effectivity yielded 100% with a complete response between 6-19 months, depending on the disease extent. Targeted questions together with imaging can speed up selection for proper treatment with colchicine, vitamin E and local treatment. Long lasting use of antibiotics and repeated surgical interventions should be avoided.

Rapid screening test of most frequent BRCA1/BRCA2 pathogenic variants in the NGS era.

The average risk of breast cancer in general Slovak population of women is 4-5% and the risk of ovarian cancer is 2%. Probability of breast/ovarian cancer development is higher in individuals carrying a causative germline DNA variant in BRCA1 or BRCA2 gene responsible for hereditary breast/ovarian cancer (HBOC). Although a major proportion of inherited breast/ovarian cancers are due to the mentioned causal mutations, a number of new genes have emerged. Here we describe a rapid, multiplex and comprehensive approach for the detection of pathogenic variants in BRCA1 and BRCA2 genes which most frequently occur in Slovak HBOC population. Analysis comprises the combination of mutation specific methods. Fluorescent PCR amplification followed by fragment analysis for detection of insertions/deletions in exon 11 of BRCA1 gene. Second method is SNaPshot analysis for detection of the most frequent missense and ins/del variants in exons 2, 5, 13, 20 of BRCA1 and exons 11, 23 and 25 of BRCA2 gene. Altogether, we have analyzed 687 samples, 86 (12.5%) in group 1, which fulfilled indication criteria based on the positive family/personal history. Group 2 involved 601 (87.5%) cases, who did not meet the indication criteria and only the screening test was recommended. Using the combined approach, we have identified 47 mutated samples (6.8%), 40 in group 1 (46.5%) and 7 in group 2 (1.1%). However, the presented screening test would not provide complex results of BRCA1/2 gene analysis, it offers testing accessible to a broader spectrum of individuals under the threshold of indication for whole gene analysis. This approach may provide valuable information even in the NGS analysis era.

A different prognostic value of BRAFV600E mutation positivity in various age groups of patients with papillary thyroid cancer.

The aim of the retrospective single-center study was to assess the prognostic value of BRAFV600E mutation positivity (BRAFV600E+) on disease persistence/recurrence in patients with papillary thyroid cancer (PTC). A total of 199 patients having had initial surgery with neck dissection in our hospital between 6/2009-6/2012 were included in the cohort. Excluded were patients with unifocal microcarcinoma ≤1cm. BRAFV600E mutation was tested from formalin-fixed paraffin-embedded surgicaly removed tumors. All included patients were postoperatively treated with radioiodine. The median duration of follow-up was 43 months, quartiles range 30 - 58 months. Variables included in the final model: BRAFV600E+, categorised age, sex, and high-risk status, or alternatively lymph node status. Based on differences in persistence/recurrence rates, patients were divided into three age categories (<35, 35-60, ≥60). Multiple regression analysis showed a significant interaction between BRAFV600E+ and age, modifying the effect of BRAFV600E+ on persistence/recurrence. BRAFV600E+ in low-risk patients of any age and in high-risk middle-aged patients did not confer additional hazard compared with BRAFV600E mutation negative (BRAFV600E-) low-risk and BRAFV600E- high-risk patients, respectively. However, younger (<35 years) and older (≥60 years) high-risk BRAFV600E+ patients had 17.28 and 33.49-fold increased hazard of persistence/recurrence, respectively, compared with low-risk BRAFV600E- patients. The alternative model including lymph node status yielded similar results for the prognostic significance of BRAFV600E+ in younger and older patients. In conclusion, the prognostic value of BRAFV600E+ depends on high-risk status and likely on age-associated factors. Such additional knowledge could change clinical decision-making in treatment modality.

The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients.

Bacterial infection is the most common complication in paediatric oncological patients during cancer treatment. A suitable tool for early prediction of unfavourable course of infection is still needed. We performed a prospective longitudinal observational study to evaluate of the role of serum biomarkers (C-reactive protein, procalcitonin, interleukin-6, presepsin) in the early diagnosis of bacteraemia (gram-negative versus gram-positive) in patients with haematological malignancies. We observed 69 febrile episodes in 33 patients (17 male, 16 female; 1.5-18.9 years, mean 7.31 years, median 5 years). Within this sample, there were 22 cases of positive blood cultures, 16 cases of sepsis, 38 cases of fever with no signs or symptoms of sepsis, and two deaths from infectious complications. All markers tested had good negative predictive value (73% - 93%). CRP was characterized by good specificity for registration bacteraemia (96%, 95% CI: 85% - 99%), but other results were inconclusive. We identified comparably balanced sensitivity (64% - 81%) and specificity (61% - 88%) for interleukin-6 and procalcitonin, and we proved their quality to predict positive blood culture and clinical signs of sepsis as well. Patients with gram-negative bacteraemia had significantly elevated levels of PCT and IL-6 in comparison with a group of patients with gram-positive bacteraemia (p = 0.04 for PCT and p = 0.005 for IL-6). Presepsin was characterized by poor specificity (27%, 95% CI: 15% - 43%) and positive predictive value (24%, 95% CI: 12 - 39%) for predicting bacteraemia, and by better sensitivity (84%, 95% CI: 55% - 98%) and specificity (58%, 95% CI: 42% - 73%) for predicting clinical signs of sepsis.

The value of SHOX2 methylation test in peripheral blood samples used for the differential diagnosis of lung cancer and other lung disorders.

Methylation of the cytosine residues within the CpG dinucleotides plays an important role in the fundamental cellular processes, human diseases and even cancer. The DNA methylation represents a very stable sign and therefore may be used as a valuable marker for cancer screening. Epigenetic cancer biomarkers are independent of classical morphology and thus show extensive potential to overcome the limitations of cytology. Several epigenetic cancer markers have been reported to be detectable in body fluids such as bronchial aspirate, sputum, plasma and serum.Short stature homeobox gene 2 (SHOX2) encodes a homeo-domain transcription factor, which has been identified as a close homologue of the SHOX gene and both genes are involved in skeletogenesis and heart development. Methylation of SHOX2 gene has been shown to be present at high prevalence in carcinomas of lung, however may also be used to identify other tumour entities.In the presented study, we have compared suitability of two types of material associated with lung cancer for the detection of SHOX2 methylation. We have confirmed that methylation of SHOX2 gene represents reliable marker of lung malignancies. The parallel tests in the blood plasma revealed that it may represent a good alternative material for testing of the SHOX2 methylation, making the test available to patients who are unable to undergo bronchoscopy.

[Stereotactic Rediosurgery for Uveal Melanoma; Postradiation Complications]. / Stereotaktická rádiochirurgia (LINAC) uveálnych melanómov; postradiacné komplikácie.

OBJECTIVE: The authors evaluate a group of patients with malignant uveal melanoma treated with stereotactic radiosurgery in the year. 2009-2011 on a linear accelerator LINAC. MATERIAL AND METHODS: In 2009-2011 were followed 40 patients with malignant melanoma of the uvea in stage T2 and T3 treated with stereotactic radiosurgery (LINAC), the therapeutic dose of 35,0 Gy TD, TD max 42,0 Gy. We evaluated the influence of factors (age, exposure risk structures, time) to intraocular pressure (IOP) and temporal changes in intraocular pressure after surgery between the control group and the group of patients who underwent enucleation. The normality of data distribution was tested Shapiro-Wilk W test and graphically. The relations between the parameters were tested using simple and multiple linear regression (correlation coefficient r, the significance level p). RESULTS: The mean age of the group of 40 patients with malignant melanoma of the uvea treated by one day session stereotactic radiosurgery on a linear accelerator in the year. 2009-2011 was 55.13±11.11 years. Average maximum radiation dose to sensitive structures has been the target of 12,0 Gy to the optic nerve and the ciliary 10,0 Gy. The analysis in our group confirmed that the prevalence of the tumor independent of sex, increasing with age, with most patients are diagnosed between 60 and 70 years of age. Analysis of the difference in intraocular pressure (IOP) before surgery showed no significant difference between the group of men and women (p=0.54). Using simple linear regression, we confirmed assumptions, related to IOP before stereotactic radiosurgery with age (r=-0.09, p=0.65). Multiple linear regression, we evaluated the relationship between predictors (dose at-risk structures--lens and optic nerve) and the change in IOP from the value before stereotactic radiosurgery at each time interval. Relations between predictors (Dose aperture--L, the dose of the optic nerve--O) and IOP of the file being described partial correlation coefficients after 2 weeks. For the relationship is significant correlation between the dose and the IOP in the lens at the time of 1 year, 1.5 years, and 2 years after the stereotactic radiosurgery. CONCLUSION: A single stereotactic radiosurgery on a linear accelerator LINAC is possible at a dose of 35,0 to 38,0 Gy in intraocular melanomas in stage T1 to T3. According to our results, this is a highly effective method of treatment of uveal melanomas elevation to 6 mm and a capacity of up to 0,4 cm3. Secondary glaucoma is one of the most serious causes of enucleation after one day session stereotactic radiosurgery at linear accelerator (LINAC) for uveal melanoma. The percentage of enucleation in our investigated group (17.5%) for secondary glaucoma is about the same as in other studies.

[Relation between carbonic anhydrase IX serum level, hypoxia and radiation resistance of head and neck cancers]. / Vztah medzi sérovou hladinou karboanhydrázy IX, hypoxiou a rádiorezistenciou nádorov hlavy a krku.

BACKGROUND: Hypoxia of locally advanced head and neck cancers is one of the main causes of their radiation resistance that presents clinically as a persistence of residual tumor disease after radiation therapy. Therefore, detection of tumor hypoxia could be an important predictor of treatment efficacy. Carbonic anhydrase IX (CA IX) is a protein, coded by a homonymous gene, the expression of which increases in tumor tissues at hypoxic conditions. Hence, CA IX represents an endogenic marker of tumor hypoxia, identifiable in tumor tissues, and its soluble extracellular domain can also be detected in body fluids of the patient. The primary endpoint of this study was to explore whether a correlation exists between CA IX serum level and the residual tumor disease after therapy. The secondary endpoint was to find out how the serum concentration of CA IX changes during the course of fractionated radiation therapy. MATERIALS AND METHODS: The presented prospective monocentric clinical study evaluated a population of 30 patients with locally advanced squamous cell head and neck cancers, treated by radiation therapy or concurrent chemo radiation therapy with a curative intent. The serum concentration of the soluble form of CA IX was examined from a venous blood sample, using sandwich enzyme linked immunosorbent assay (ELISA). The blood samples were obtained before the treatment initiation, in the middle of radiation therapy, at the time of finishing radiation therapy and six weeks after the treatment completion. RESULTS: We found a substantial variability in the CA IX levels measured in the examined population, ranging 0- 1,696 pg/ ml. We found no significant changes in the mean value of CA IX concentration during the course of radiation therapy and after the treatment completion. In 11 patients (36.7%), the treatment resulted in complete remission of the disease. In these patients, lower average pretreatment levels of CA IX were noted when compared to patients with persistence of residual tumor disease (37.57 vs 77.47; p = 0.154). CONCLUSION: The results indicate that serum level of CA IX in patients with locally advanced head and neck cancers does not change significantly during the course of fractionated radiation therapy. The relation between CA IX serum level and residual tumor disease after radiation therapy requires verification on a larger population of patients.

Transvaginal ultrasound examination of myometrial infiltration by endometrial cancer.

The depth of myometrial infiltration by endometrial cancer is an important prognostic factor. The examination of the depth of infiltration classifies the patients in the low- and high-risk groups, which influences the therapeutic approach. Transvaginal ultrasonography represents a first-choice diagnostic test for the assessment of the depth of myometrial infiltration as the time consumption and financial demands of magnetic resonance imaging need to be taken into account. In comparison with the MRI, the diagnostic accuracy of the transvaginal ultrasound depends more on the individual experience and professional potential of the examining physician. This fact can contribute to the heterogeneity of published results of transvaginal ultrasound on the determination of infiltration depth. Having in mind the aim to verify these indicators in our local conditions and environment, we decided to prospectively study 150 endometrial cancer patients who were examined with the transvaginal ultrasound in the period 1/2009 - 10/ 2011. Correlated firstly with the preoperative and then secondly with the definitive histopathological examination was the depth-of-infiltration-related data that had been taken from the ultrasound findings. The output being monitored was the exclusion or confirmation of the invasion exceeding half the thickness of myometrium. In our study, the diagnostic accuracy of the method reached 82.67 %, while the other indicators were as follows: sensitivity 92.31 %, specificity 79.28 %, positive predictive value (PPV) 61.02 %, negative predictive value (NPV) 96.7 %, the likelihood ratio of a positive test 4.455 and the likelihood ratio of a negative test 0.097. The results of the depth of myometrial infiltration examination and their comparison with the data from similarly oriented clinical studies entitle us to include this examination in the set of standard preoperative methods used for the examination of patients with endometrial cancer (Tab. 3, Fig. 5, Ref. 20).

Dual influence of spontaneous hypertension on membrane properties and ATP production in heart and kidney mitochondria in rat: effect of captopril and nifedipine, adaptation and dysadaptation.

This study deals with changes, induced by hypertension and its treatment, in the function and properties of mitochondria in the heart and kidneys. Male, 16-week-old hypertensive rats were allocated to 3 groups: (i) animals treated daily for 4 weeks with captopril (CAP, 80 mg·(kg body mass)(-1), n = 45), (ii) animals treated with CAP + nifedipine (NIF, 10 mg·kg(-1), n = 45), or (iii) untreated hypertensive controls (n = 96). Wistar rats (n = 96) were used as normotensive controls. Systolic blood pressure (SBP), heart rate (HR), and heart mass / body mass (HW/BW) ratio were measured at the beginning and end of the experiments; measurements for mitochondrial Mg(2+)-ATPase activity, O(2)-consumption (QO(2)), respiratory control index (RCI), ADP/O, oxidative phosphorylation rate (OPR), conjugated diene content (CD), and membrane fluidity (MF) were also taken at different time intervals. In the heart, elevated SBP, HR, and HW/BW accompanied increased QO(2), OPR, and Mg(2+)-ATPase activity, indicating an adaptive response to hypertension-induced increase in the energy demands of the myocardium. Treatments with CAP or with CAP + NIF were very similar in their prevention of increase in SBP, HR, HW/BW, and the rise in OPR (all p < 0.05-0.01). In the kidneys, hypertension induced a drop in OPR; however, antihypertensive therapy aggravated the resulting energy deficiency, whereby treatment with CAP + NIF was more detrimental than treatment with CAP alone. Heart and kidney mitochondria exhibited negligible changes in CD and moderately increased MF, which was more potentiated by treatment with CAP alone than with CAP + NIF.

Influence of infection on clinical picture of diabetic foot syndrome.

The aim of our study was to analyse the foot infections in diabetic patients. We analysed foot ulcerations in 124 diabetics who attended outpatient foot clinic, or were hospitalized in the period from 1996 to 2006. Basic neuropathy screening examination was made with cotton wisp, pin-prick, tuning fork, and monofilament. For evaluation of leg ischemia, besides the evaluation of the presence of pedal pulses, the ankle-brachial pressure index was measured. If the infection of foot ulceration was clinically present, bacteriology examinations was performed. In the case of deep wound infection, x-ray examination was made. If bone destruction was present, osteomyelitis was diagnosed by technecium bone scanning and by technecium-labelled leukocyte scan. Deformation and destruction of the bone without infection was appoited as Charcot neuroarthropathy. Foot ulcer infection was found in 58 % diabetic patients, wounds were more often deep (80 %). Infection was not associated with special location of foot ulcer. Two-third of the total infected wounds were associated with leg ischemia and 30.6 % of infected ulcer ended with leg amputation. More foot ulcer infections were found in the diabetics with HbAlc over 8 %. Infection was coupled with diabetic retinopathy (in 63 % patients) (p=0.023), and also with diabetic nephropathy (in 66 % patients) (p=0.012). Bacteriology examination revealed most often Staphylococci (45.8 %), antibiotic therapy was made most often with chinolones. Osteomyelitis was present in 34.7 % of foot ulcer infections. In 14 diabetics (56 %) after antibiotic therapy it was not necessary to perform a leg amputation. HbAlc seems to be a significant predictor of osteomyelitis (p<0.02; OR=1.76). In conclusion, we confirmed that diabetic foot infections, especially on ischemic leg, in diabetics with poor metabolic control and chronic diabetic microvascular complications, are associated with a higher risk of leg amputations. Further, it is possible to cure osteomyelitis successfully without surgery in more than half the cases (Tab. 1, Ref. 24). Full Text in free PDF www.bmj.sk.

No differences in outcome between radical surgical treatment (enucleation) and stereotactic radiosurgery in patients with posterior uveal melanoma.

To report the treatment outcome and possible survival difference between radical surgical treatment (enucleation) or stereotactic radiosurgery (SRS). LINAC stereotactic radiosurgery is an alternative treatment for posterior uveal melanoma used in Slovakia since 1999. The study analyzed patients treated for posterior uveal melanoma in the period 2001-2008. The aim of the study was to compare the relapse-free survival in the cohort of patients primarily treated with surgery (enucleation) or SRS. A total number of 84 patients were included, treatment was determined on a case-by-case basis. We reviewed the records of patients with ciliary body or choroidal melanoma treated by enucleation - 44 patients (52%) and SRS - 40 patients (48%). The therapeutic attitude was established on the basis of ophthalmoscopy, ultrasound (A, B mode), other ophthalmological findings, visual acuity, and general status of each patient. Volume of the tumor was calculated using the formula: "pi/6 x length x width x height" for each patient. All of the patients before decision to "conservative" attitude therapy underwent MRI examination. The therapeutic dose in SRS patients group was 35.0-38.0 Gy. The data were analyzed using Kaplan - Meier survival method for the differences in survival rates between the treatment groups, and afterwards by Cox s proportional hazard method with predictors involved. Among the baseline covariates evaluated, only age affected the prognosis for survival to a statistically important, however not significant degree. The risk of death among patients treated with enucleation relative to those treated with stereotaxy after adjustment for baseline characteristics of patients, age, and tumor volumes was not significant [1.82] (95% CI, 0.46 to 7.30; P = 0.396). The overall five-year survival rate for patients with posterior uveal melanoma was 72%. Treatment by either primary enucleation or SRS according to our results does not appear to influence the development of metastases in patients with uveal melanoma; the survival prognosis is essentially determined by the stage and character of the tumor. No survival difference attributable to stereotactic irradiation of uveal melanoma has been demonstrated in this retrospective study. A small difference is possible, but a clinically meaningful difference in mortality rates, whether from all causes or from metastatic melanoma, is unlikely. Treatment by either radical surgical attitude (enucleation) or "conservative" LINAC- SRS does not appear to influence the survival rate in patients with uveal melanoma.

Seasonal variations in properties of healthy and diabetic rat heart mitochondria: Mg2+-ATPase activity, content of conjugated dienes and membrane fluidity.

Our previous preliminary results pointed to possible seasonal variations in Mg2+-ATPase activity of rat heart mitochondria (MIT). It is not too surprising since seasonal differences were already reported in myocardial function, metabolism and ultrastructure of the intact as well as hemodynamically overloaded rabbit hearts and also in other tissues. The present study is aimed to elucidate whether seasonal differences observed in rat heart MIT Mg2+-ATPase activity will be accompanied with changes in membrane fluidity and in the content of conjugated dienes (CD) in the lipid bilayers of MIT membranes as well as whether the above seasonal differences will also be present in the diabetic heart. Our results revealed that values of Mg2+-ATPase activity in the winter/spring-period (W/S-P) exceeded significantly (p<0.05-0.001) those in the summer/autumn-period (S/A-P). Similar trend was also observed in hearts of animals with acute (8 days) streptozotocin diabetes. With the exception of values of CD in the S/A-P, all values of Mg2+-ATPase activities, membrane fluidity and CD concentrations in diabetic hearts exceeded those observed in the healthy hearts. Our results indicate that seasonal differences may play a decisive role in the evaluation of properties and function of rat heart MIT.

Endogenous protective mechanisms in remodeling of rat heart mitochondrial membranes in the acute phase of streptozotocin-induced diabetes.

The aim of present study was to investigate functional and physical alterations in membranes of heart mitochondria that are associated with remodeling of these organelles in acute phase of streptozotocin-induced diabetes and to elucidate the role of these changes in adaptation of the heart to acute streptozotocin-induced diabetes (evaluated 8 days after single dose streptozotocin application to male Wistar rats). Action of free radicals on the respiratory chain of diabetic-heart mitochondria was manifested by 17 % increase (p<0.05) in oxidized form of the coenzyme Q(10) and resulted in a decrease of states S3 and S4 respiration, the respiratory control index, rate of phosphorylation (all p<0.01) and the mitochondrial transmembrane potential (p<0.05), but the ADP/O ratio decreased only moderately (p>0.05). On the contrary, membrane fluidity and the total mitochondrial Mg2+-ATPase activity increased (both p<0.05). In diabetic heart mitochondria, linear regression analysis revealed a reciprocal relationship between the increase in membrane fluidity and decrease in trans-membrane potential (p<0.05, r = 0.67). Changes in membrane fluidity, transmembrane potential, Mg2+-ATPase activity and the almost preserved ADP/O ratio appear as the manifestation of endogenous protective mechanisms participating in the functional remodeling of mitochondria which contributes to adaptation of the heart to diabetes.

The effect of Pycnogenol on the erythrocyte membrane fluidity.

In the present study, the in vitro effect of polyphenol rich plant extract, flavonoid--Pycnogenol (Pyc), on erythrocyte membrane fluidity was studied. Membrane fluidity was determined using 1-[4-trimethyl-aminophenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), 1,6-diphenyl-1,3,5-hexatriene (DPH) and 12-(9-anthroyloxy) stearic acid (12-AS) fluorescence anisotropy. After Pyc action (50 microg/ml to 300 microg/ml), we observed decreases in the anisotropy values of TMA-DPH and DPH in a dose-dependent manner compared with the untreated erythrocyte membranes. Pyc significantly increased the membrane fluidity predominantly at the membrane surface. Further, we observed the protective effect of Pyc against lipid peroxidation, TBARP generation and oxidative hemolysis induced by H2O2. Pyc can reduce the lipid peroxidation and oxidative hemolysis either by quenching free radicals or by chelating metal ions, or by both. The exact mechanism(s) of the positive effect of Pyc is not known. We assume that Pyc efficacy to modify effectively some membrane dependent processes is related not only to the chemical action of Pyc but also to its ability to interact directly with cell membranes and/or penetrate the membrane thus inducing modification of the lipid bilayer and lipid-protein interactions.