Institute for Postgraduate Medical Education

Prague, Czech Republic

Institute for Postgraduate Medical Education

Prague, Czech Republic
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Lejskova M.,Institute for Postgraduate Medical Education | Lejskova M.,Thomayer Hospital and Outpatient Clinic | Alusi S.,Institute for Postgraduate Medical Education | Alusi S.,Thomayer Hospital and Outpatient Clinic | And 3 more authors.
Physiological Research | Year: 2012

Cardiovascular disease, while rare in women of reproductive age, is the main cause of mortality in menopause. The purpose of our study was to determine the association of natural menopause with cardiovascular risk factors, including their clustering into metabolic syndrome (MS). A random 5 % representative population sample of women aged 45-54 years was examined. In 575 women, we were able to determine their natural reproductive aging status. Multiple regression analysis was used to calculate the association between age, menopausal status, and risk factors under study. After adjustment for age, there was an increase in the odds ratio of developing MS, as defined by NCEP (OR=2.0; 95 % CI [1.1; 3.7]), and an increase in plasma lipid ratios (total cholesterol/HDL-C, LDL-C/HDL-C, apolipoprotein-B/ apolipoprotein-A1; p<0.05 for all) in postmenopausal women. Age, but not menopausal status, was associated with some single components of MS; only waist circumference significantly increased after menopause, independently of age. Clustering of risk factors in MS and lipid ratios (combined factors) was strongly associated with menopause whereas worsening of single components of MS was strongly associated with age. In conclusion, based on our results, the menopause may pose a risk to women through clustering of cardiovascular risk factors beyond simple aging. © 2012 Institute of Physiology v.v.i.


Chrbolka P.,Thomayer Hospital | Paluch Z.,Charles University | Hill M.,Institute of Endocrinology | Alusik S.,Institute for Postgraduate Medical Education
Steroids | Year: 2017

While not a disease entity in itself; symptoms of tinnitus (from Latin tinnio – clink) accompany a number of diseases. Tinnitus prevalence increases with age, deteriorates one's quality of life, and may even result in suicidal behavior. Tinnitus develops in response to a variety of risk factors, otoxic substances, noise exposure, hearing disorders, and psychological alterations. Tinnitus is closely related to mood, depression, and psychological state. In the present study, we focused on alterations of the steroid metabolome and particularly neuroactive, neuroprotective, and immunomodulatory steroids in patients with tinnitus. The study group consisted of 28 patients without evidence of an organic cause of tinnitus as well as without associated diseases or the effect of ototoxic medications. All patients underwent a complete audiological assessment and laboratory tests including routine biochemical markers and quantification of circulating steroids using gas chromatography/mass spectrometry and immunoassays. To rule out a pathology in the cerebellopontine angle area, CT scan or MRI were performed. To diagnose stem lesions, evoked potentials were also measured. Pearson's correlations and multivariate regression were used to assess any links between tinnitus intensity and frequency on the one hand, and steroid levels on the other. Results indicated a significant and consistent negative correlation between tinnitus indices and intensity of adrenal steroidogenesis. The circulating steroid metabolome including hormones and neuroactive, neuroprotective, and immunomodulatory steroids negatively correlates with the degree of tinnitus due to hypothalamo-pituitary-adrenal axis malfunction. Our results may help explain the pathophysiology of tinnitus and improve its diagnosis. However, further studies are needed to verify our postulation. © 2017 Elsevier Inc.


Zavoral M.,Charles University | Zavoral M.,Central Military Hospital | Zavoral M.,Institute for postgraduate medical education | Minarikova P.,Charles University | And 8 more authors.
World Journal of Gastroenterology | Year: 2011

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment. © 2011 Baishideng. All rights reserved.


Pitha J.,Institute for Clinical and Experimental Medicine | Lesna K.,Institute for Clinical and Experimental Medicine | Sekerkova A.,Institute of Clinical and Experimental Medicine | Poledne R.,Institute for Clinical and Experimental Medicine | And 6 more authors.
International Journal of Cardiology | Year: 2013

Background: The presence of cardiovascular risk factors during the menopausal transition could be critical in the development of atherosclerosis. In the present study, we evaluated whether the menopausal transition has impact on traditional and newly discussed risk factors. Methods: Six hundred ninety nine women from population-based study underwent ultrasound measurement of the intima-media thickness of the common carotid arteries (CIMT) - Prague Pre and Postmenopausal Females study (3PMFs). In addition, 40 women selected according to reproductive and smoking status were examined with regard to number of circulating endothelial progenitor cells, markers of reverse cholesterol transport and sex hormones, including their fluctuation - Hormone Variability study (HVs). Results: Age, smoking, body mass index, systolic blood pressure and HDL cholesterol were independently associated with the CIMT in 3PMFs group. The increase in the CIMT with age was markedly steeper in current/past smokers than in non-smokers among perimenopausal women (p for equality of slopes = 0.005). This difference was not observed in premenopausal and menopausal women. In the HVs group, endothelial progenitor cells and reverse cholesterol transport were substantially higher while triglycerides and fluctuation of free testosterone were lower in non-smokers than in smokers in menopausal transition. In contrast, in menopausal women, the fluctuation of free testosterone was higher in non-smokers; no other differences between smokers and non-smokers were detected. Conclusions: These results suggest that atherogenic effect of smoking may be enhanced during menopausal transition. The mechanism could be impaired reparative vascular processes, impaired reverse cholesterol transport and rapidly changing status of sex hormones. © 2012 Elsevier Ireland Ltd. All rights reserved.


Alusik S.,Institute for Postgraduate Medical Education | Paluch Z.,Charles University | Paluch Z.,St. Elizabeth College of Health and Social Work | Paluch Z.,St J N Neumann Institute Pribram
Minerva Medica | Year: 2015

The authors trace the history of metformin and its clinical use to the present day. Recent insights into its mode of action and latest data from experimental and clinical medicine have unraveled novel properties of metformin, which may be particularly useful in the treatment of conditions other than diabetes. Results of ongoing clinical trials will show whether or not the hypoglycemic effect of metformin will become only one of the many to be employed in clinical practice.


Levy M.,Charles University | Benesova L.,Applied Genomics | Lipska L.,Charles University | Belsanova B.,Applied Genomics | And 7 more authors.
Anticancer Research | Year: 2012

Background: While efficient surgical treatment is the key to prolonged survival of patients with colorectal cancer, post-surgical follow-up is important for the early detection of relapsing disease or of disease progression. Current dispensarization, typically based on imaging CT, PET, MR, is frequently supported by the observation of tumour markers (CEA, CA19-9). Due to their limited sensitivity and selectivity, better tools for monitoring of the disease are desirable. Tumour cell-free DNA (cfDNA) has been recently demonstrated as a new promising molecular marker for observation and early detection of disease progression. Patients and Methods: We present results of post-surgical monitoring tumour cfDNA in the cases of seven patients suffering from advanced forms of CRC. We applied a mutation-based approach in which the total cfDNA was screened for a specific somatic mutation present in the primary tumour. We screened a panel of the most frequent somatic mutations covering the genes APC, KRAS, TP53, PIK3CA and BRAF. All patients were tested positive for tumour cfDNA prior to surgery. cfDNA was then evaluated within a week after surgery and subsequently in monthly intervals. Results: We present typical cases of colorectal cancer patients who underwent surgical treatment at different levels of radicality with or without adjuvant chemo/biotherapy. The tumour cfDNA status was found to be always closely correlated with the actual clinical status of the patient. Conclusion: The cfDNA appears to be a viable tool for the monitoring of the clinical progression of CRC in patients with cfDNA positivity prior to surgery.


Alusik S.,Thomayer University Hospital | Alusik S.,Institute for Postgraduate Medical Education | Paluch Z.,Thomayer University Hospital | Lejskova M.,Thomayer University Hospital | Adamek T.,Thomayer University Hospital
International Angiology | Year: 2010

Aim. Elevated urinary 11-dehydrothromboxane levels place patients at an increased risk for experiencing cardiovascular events. Statins exert an inhibitory effect on platelets. The aim of our study was to determine the effect of 3-month statin therapy on 11-dehydrothromboxane elimination in two groups of patients, one not receiving antiplatelet therapy with acetylsalicylic acid and the other receiving 100 mg acetylsalicylic acid per day. Methods. We examined the urinary levels of 11-dehydrothromboxane in a total of 58 patients before and after 3-month therapy with a statin at standard doses (simvastatin, fluvastatin, atorvastatin). We also examined the plasma levels of total cholesterol, triglycerides, LDL- and HDL-cholesterol, C-reactive protein, and blood glucose. Results. After 3-month statin therapy, both groups of patients (with and without antiplatelet therapy) showed a significant decrease in urinary 11-dehydrothromboxane levels. Significant decreases were also seen in LDL- and total cholesterol, and C-reactive protein. Changes in the other parameters were not significant. Conclusion. Three-month statin therapy significant reduces the rate of 11-dehydrothromboxane elimination, even in patients on acetylsalicylic acid. In addition to its usual lipid-lowering effect, it significantly decreases the plasma levels of C-reactive protein. Combination therapy with a statin plus acetylsalicylic acid may be effective even in patients with incomplete thromboxane inhibition on antiplatelet therapy with acetylsalicylic acid.


Sedlacek J.,General Teaching Hospital | Kocvara R.,General Teaching Hospital | Kocvara R.,Institute for Postgraduate Medical Education | Molcan J.,General Teaching Hospital | And 3 more authors.
Journal of Pediatric Urology | Year: 2010

Objective: To compare the transmesocolic approach in the left laparoscopic pyeloplasty with the laterocolic right-side repair in children. Patients and methods: Dismembered pyeloplasty was performed in 77 consecutive children aged 1.2-18.2 years. The transmesocolic approach was used in 49 patients with left hydronephrosis (group I) and the conventional laterocolic approach in 28 patients with right hydronephrosis (group II). Three age groups were defined. Results: The transmesocolic approach was applicable in 48 of 49 patients (98%); the colic vessels were preserved. The operation time was significantly shorter in the transmesocolic group, also when comparing patients with similar age, incidence of crossing vessels and urinary diversion. A shorter operation time was achieved in children without internal urine diversion. Postoperative complications were encountered in 6.3% of group I and 7.1% of group II without any conversion to open repair or recurrence of obstruction within a 2.5-year follow-up period. Conclusions: The transmesocolic approach offers clear anatomy and provides safe access to the dilated left renal pelvis and crossing vessels. The operative time is shorter due to very limited tissue dissection. The medial reflection of the colon is avoided. This approach allows for microsurgical performance of the left-side pyeloplasty in all paediatric age groups. © 2009 Journal of Pediatric Urology Company.


Lejskova M.,Thomayer Hospital | Lejskova M.,Institute for Postgraduate Medical Education | Pitha J.,Institute for Clinical and Experimental Medicine | Adamkova S.,Institute for Clinical and Experimental Medicine | And 5 more authors.
Physiological Research | Year: 2014

The incidence of diabetes mellitus is rising worldwide. The aim of this prospective epidemiological study was to compare the effects of natural and surgical menopause on parameters of glucose metabolism. In a group of 587 repeatedly examined women, with a baseline age of 45-55 years, the following subgroups of women were separated: those after bilateral oophorectomy (BO, n=37) and those in natural menopause (NAT, n=380) including women menopausal already at baseline (POST, n=89). The study parameters including glycemia, insulinemia, HOMA-IR and betacell function using HOMA-β were determined at baseline and 6 years later. Over the study period, there was a marked rise in prediabetic and diabetic values of fasting glycemia; the percentage of women with diabetic values increased in the NAT (from 0.8 % to 3.9 %) and POST (from 2.2 % to 9.0 %) subgroups, with the highest prevalence in the BO subgroup (from 8.1 % to 10.8 %). While, among women with non-diabetic fasting glycemia, an increase in fasting glycemia was observed in all study subgroups, it was more marked in the BO subgroup than in the NAT and POST ones (p=0.02 both). This difference between NAT and BO was also found in the long-term trend of development of glycemia in non-diabetic women (p=0.014). Compared with natural menopause, bilateral oophorectomy may have an adverse effect on glucose metabolism. © 2014 Institute of Physiology v.v.i.


PubMed | Institute for Postgraduate Medical Education
Type: Journal Article | Journal: Physiological research | Year: 2013

Cardiovascular disease, while rare in women of reproductive age, is the main cause of mortality in menopause. The purpose of our study was to determine the association of natural menopause with cardiovascular risk factors, including their clustering into metabolic syndrome (MS). A random 5 % representative population sample of women aged 45-54 years was examined. In 575 women, we were able to determine their natural reproductive aging status. Multiple regression analysis was used to calculate the association between age, menopausal status, and risk factors under study. After adjustment for age, there was an increase in the odds ratio of developing MS, as defined by NCEP (OR=2.0; 95 % CI [1.1; 3.7]), and an increase in plasma lipid ratios (total cholesterol/HDL-C, LDL-C/HDL-C, apolipoprotein-B/apolipoprotein-A1; p<0.05 for all) in postmenopausal women. Age, but not menopausal status, was associated with some single components of MS; only waist circumference significantly increased after menopause, independently of age. Clustering of risk factors in MS and lipid ratios (combined factors) was strongly associated with menopause whereas worsening of single components of MS was strongly associated with age. In conclusion, based on our results, the menopause may pose a risk to women through clustering of cardiovascular risk factors beyond simple aging.

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