Biomedical subjects

J Novotný

Publications and source records attributed to J Novotný.

At least 19 recordsLinked to original sources

PubMed2006

Re-fixation in a lymph node revealing solution is a powerful method for identifying lymph nodes in colorectal resection specimens.

AIM: To verify an impact of a lymph node revealing solution (LRS) on the number of lymph nodes (LN) revealed in colorectal resection specimens. MATERIAL AND METHOD: Fifty-nine cases of rectosigmoid carcinomas divided into two subgroups-stage pT2&3 (20 cases) and ypT2&3 (with pre-operative radiotherapy-39 cases)-were formalin fixed for 42-72 h, serially sectioned and re-fixed in LRS containing ethanol, diethyl ether, glacial acetic acid, and formalin for 24 h. The number of LNs was matched to a control group consisting of 34 cases of colorectal carcinoma, 14 pT2&3 and 20 ypT2&3 rectosigmoid carcinomas examined routinely. Results were statistically tested by Student's t-test. RESULTS: In the study group the total number of revealed LNs was 869, range 1-48, average 14.7 per specimen, median 15. In the control group the number of LNs was 200, range 0-13, average 5.9 per specimen, median 6. The difference between the study and the control group was statistically significant (P = 0.05). CONCLUSION: Using LRS leads to a significant increase in the number of revealed LNs in colorectal resection specimens and makes it possible to find more than 12 LNs in a majority of stage pT2 and pT3 adenocarcinomas.

Acetic Acid↗

PubMed2006

[Heparin induced thrombocytopenia].

This article describes the pathogenesis, diagnostics, treatment and prevention of heparin induced thrombocytopenia (HIT). Although HIT is considered to be a hematological diagnosis, every physician who treats patients with heparin can encounter it in daily practice. It is even more probable that surgeons of any specialisation will meet with HIT patients. A section of them elude diagnostic detection. There are two forms of HIT - HIT I and HIT II. HIT I is caused by a direct pro-aggregation effect of heparin. It has no clinic significance. HIT II is an antidote mediated adverse reaction to heparin. Antidotes will generate only after the exposure to heparin. They are targeted against the platelet factor 4 and they act only at the presence of heparin. They may lead to the aggregation of thrombocytes in the vascular system (there is a decrease in thrombocyte count). This event can be accompanied by a development of venous or arterial thrombosis that can have a rapid and even fatal course. This fact clarifies the importance of HIT II diagnostics. Diagnosis of HIT II is based on recognizing of the typical decrease in thrombocyte count usually 1 day after heparin administration is initiated. Clinical manifestations are more likely in patients with already damaged endothelium. If thrombocyte count decrease is not connected with clinical manifestations, it is the so called isolated HIT II and in patients who display the signs of thrombosis, it is HIT II associated with thrombosis. The goal of this article is apart from implementing the recommendations of the 7th conference of the American Respiratory Society in real life also the exploration of the diagnostic and therapeutic limits (availability) in the Czech Republic.

Anticoagulants↗

PubMed2006

Preoperative radiotherapy for locally advanced rectal cancer and prognostic factors influencing outcome.

The aim of presented study was to evaluate the impact of different factors on survival, local recurrence and development of metastatic disease in patients with rectal cancer treated with preoperative radiotherapy or 5-fluorouracil (5-FU) based concurrent chemoradiation. Retrospective clinical evaluation was performed in 165 patients (33% women and 67% men) with locally advanced rectal adenocarcinoma treated with preoperative radiotherapy or chemoradiotherapy in the period January 1998 - March 2003. Tumor extent was evaluated by CT and/or MRI and/or TRUS examination and tumor biopsy was performed during colonoscopy. The median follow up is 21 month. All patients received preoperative external beam radiation to primary tumor, adjacent lymphnodes and presacral region. Computed tomography localisation of target volume was used for 3D radiotherapy treatment planning. Accelerated short term regimen (25 Gy/5 fraction/1 week) was performed in 14% of patients especially in year 1998-2000 and normofractionated regimen (40-50 Gy/20-25 fractions/4-5 weeks) was performed in 86% of patients. Chemoradiotherapy with 5-FU was carried out in 22% of patients. Radical resection underwent 85% of patients, inoperable tumor persisted in 7% and distant metastases were detected peroperatively in 8%. The 2-year overall survival (OS) was 84% and 5-year OS was 60% following radical resection. The important prognostic factors affecting survival were postradiotherapy determined pathological staging (p=0.005), postradiotherapy tumor grade (p<0.001) and the presence of angioinvasion and/or perineural spread (p=0.023). Prognostic factors for disease-free survival were identical with those for OS. Higher local recurrence rate was associated in preradiotherapy tumor staged T4 (p=0.048) and in presence of angioinvasion and/or perineural spread (0.049). Age, tumor location, histological grade before radiotherapy and tumor downstaging were not statistically significant for survival and/or for local recurrence rate. The best survival rates were obtained in patients with postradiotherapy grade 1 tumors (5-years survival 100%), tumors without angioinvasion and perineural spread (5-years survival 65%) and in patients who obtained complete remission after preoperative radiotherapy (5-years survival 86%).

Combined Modality Therapy↗

PubMed2006

[Prediction of treatment outcome after adjuvant loco-regional chemotherapy following liver resection for colorectal metastases--preliminary results].

INTRODUCTION AND AIM OF STUDY: Czech Republic leads the worldwide league in colorectal cancer's occurrence. Colorectal liver metastases are detected in about a half of patients with colorectal cancer. Liver resection of colorectal metastases is currently the only potentially curative treatment with a chance for a long-term survival rate. Until now there has remained a question of whether adjuvant HAIC can improve the treatment results of radical resection. The aim of our study is to verify predictive efficiency of thymidylátsyntasis (TS), dihydropyrimidindehydrogenasis (DPD) and thymidinfosforylasis (TP) in patients undergoing adjuvant hepatic artery infusion chemotherapy (HAIC) following radical liver resection for colorectal metastases. METHODS: From 1990 to 2005 80 patients underwent 84 liver resections for colorectal metastases. R0 resection was achieved in 60 events. Ten patients who underwent R0 resection both for primary cancer and for colorectal liver metastases and who were given portcatheter for HAIC were included in this study. Adjuvant chemotherapy contained 5-fluorourycil (1200 mg/m2) combined with oxyliplatinum and leukovorin. Whole dose was administered via hepatic artery. The samples were procured both from healthy liver tissue and from metastases for imunohistochemical and molecular biological analysis. RESULTS: The recurrence of disease was verified in 2 of 10 included patients (20%). We detected neither occurrence of death nor serious complication in early postoperative course in none of ten patients. Low expression of TS was found in both events and very high expression of DPD in one event was detected. DISCUSSION: High expression of DPD in one of these patients could contribute to lower outcome of adjuvant chemotherapy. Low expression of TS in both patients responds to the written statement regarding contribution of adjuvant chemotherapy only in patients with high TS level. CONCLUSION: The expression of TS and DPD responds to expected outcome of HAIC. Low number of patient does not permit statistic evaluation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

[The analysis of preliminary spermatological parameters in potential donors of semen].

OBJECTIVE: To contribute to the contemporary discussion on the male factor infertility through the evaluation of the basic spermatological parameters in men recruiting for semen donation. DESIGN: A retrospective demographic study. SETTING: Dept. of Obstetrics and Gynaecology, Dept. of Biology, Faculty of Medicine, Palacký University, Olomouc. METHODS: A total of 108 men aged 18 to 35 years came to the preliminary examination for the potential semen donors between January 2000 and April 2004. Spermatological analysis of the fresh ejaculates obtained by masturbation was performed according to WHO guidelines. The following parameters were evaluated: the volume of ejaculate, sperm concentration and total percent motility. RESULTS: Normospermia was found in only 46 men (42.6%). Three males (2.8%) were azoospermic. The most frequent problem was asthenospermia, which was documented in 49 (46.6%) men. CONCLUSION: The analysis of the obtained data may suggest a marked semen quality decline in the Czech male population. In our opinion, further multicentric epidemiological studies concerning fertility potential in Czech male population seem highly needed.

Adolescent↗

PubMed2005

[On the problem of sentinel lymphatic nodes examination in mammary cancer].

OBJECTIVE: Evaluation of present approaches to the investigation of sentinel lymph nodes in breast cancer. DESIGN: A review article. SETTING: Obstetrics and Gynecology Department, Institute of Pathology and Department of Clinical Oncology of 1st Faculty of Medicine and General Teaching Hospital, Prague. SUBJECT: Sentinel lymph node biopsy can change surgical management of breast cancer and evaluation of regional lymph nodes. Sentinel nodes are reached first by the process of metastasis. Their status has been shown to rather accurately reflect the presence or absence of metastases in the axillary lymph nodes. The macrometastases (larger than 2 mm) are the most important ones. Step or serial sectioning and cytokeratins detection are necessary for findings of micrometastases (0.2-2 mm) or isolated tumor cells. Their prognostic significance is until now unclear and standard examination does not exist. CONCLUSION: Pathological examination of sentinel lymph nodes ought to identity all macrometastases (larger than 2 mm) as a minimum standard. Further investigations are necessary in order to evaluate the significance of micrometastases and isolated tumor cells and to find an optimal and standard processing.

Breast Neoplasms↗

PubMed2005

[The risk of malignancy after organ transplantation].

Improvements in immunosuppressive therapy during the past decade brought about improvements of the long term tolerance of organ allografts. However, the long-term immunosuppressive therapy has an important limitation, because it can increase the risk of cardivascular diseases, infections and tumors. As compared with age-matched healthy population, organ-transplant recipients have an increased incidence of tumors.

Humans↗

PubMed2005

[Exenteration procedures in the pelvis].

Exenteration pelvic procedures are surgical options for treatment of locally advanced pelvic tumors. Due to the procedure's success rates, it has become a standard therapeutic procedure, when indicated. From the medical point of view, the following factors characterize the level of seriousness of these procedures: the fact that the procedure is extensive, its complicated reconstruction phase and high postoperative morbidity rates. From the patient's point of view, it is characterized by a principal change in the quality of life. In this case review the authors present their experience with a multidisciplinary approach to these procedures.

Adult↗

PubMed2004

Gamma knife radiosurgery of skull base meningiomas.

Meningiomas are the most frequent benign tumors treated by gamma knife radiosurgery and the majority of them are located on the skull base. Between 1992 and 1999, 197 skull base-located meningiomas in 192 patients were treated by gamma knife in Prague. Contact with the chiasma or optic tract was not regarded as a contraindication for gamma knife radiosurgery and such contact was observed in 32% of the skull base meningiomas treated. 176 patients were monitored during a median of 36 months, of whom 73% showed a decrease in tumor volume; no change was observed in 25% and continued growth was observed in 2%. Neurodeficit improved in 63% of patients, temporary morbidity occurred in 11% and persistent morbidity remained in 4.5%. Radiosurgery induced edema in 11%. Significantly lower edema occurrence was observed after radiosurgery in patients with no history of edema prior to radiosurgery, where the tumor was located in the posterior skull base and where the dosage to the tumor margin was lower than or equal to 14 Gy. Radiosurgery of skull base meningiomas has been proven to be safe and efficient. We consider gamma knife treatment for skull base meningiomas to be the method of choice whenever tumors are within the volume limits and there is no need for an urgent decompressive effect from the open operation.

Adult↗

PubMed2004

[Pancreatic carcinoma and diabetes mellitus].

BACKGROUND: The aim of the present study was to evaluate the relationship between Pancreatic Cancer and Type 2 Diabetes Mellitus, which represents a higher risk of many human tumors. In patients with Pancreatic Cancer, Type 2 Diabetes Mellitus occurs approximately in 30%. METHOD AND RESULTS: Fifty patients with newly diagnosed Pancreatic Cancer were analysed in a retrospective pilot study where the staging of the tumor and the case history of the patients were studied. This data were compared in three groups of patients: the control group without diabetes, one with Impaired Fasting Glucose, and patients with Diabetes Mellitus. Incidence of Diabetes Mellitus and that of Impaired Fasting Glucose were also followed in patients with Pancreatic Cancer and Colorectal Cancer. The retrospective study confirmed the late diagnosis of Pancreatic Cancer. The tumors were actually in clinical stage IV in 50% of the patients. Diabetes Mellitus was present in 34% of patients with Pancreatic Cancer; in 44% of these patients the Impaired Fasting Glucose was also diagnosed while the normal glucose status was seen in 22% of patients. Incidence of Impaired Fasting Glucose and that of Diabetes Mellitus in groups of patients with Pancreatic Cancer and Colorectal Cancer was studied. Diabetes Mellitus was present in 12.5% patients with Colorectal Cancer. CONCLUSIONS: In spite of modern diagnostic methods, the early diagnosis of Pancreatic Cancer remains a great problem. Incidence of Diabetes Mellitus in patients with Pancreatic Cancer was significantly higher in comparison with the Colorectal Cancer group (P0.01). A significant number of patients with Impaired Fasting Glucose were also present in the group with Pancreatic Cancer. Analysis of the relationships between Pancreatic Cancer and Impaired Glucose Metabolism could contribute to the early diagnosis of this serious malignant disease.

Adult↗

PubMed2004

Biochemistry of transmembrane signaling mediated by trimeric G proteins.

Many extracellular signals are at the cell surface received by specific receptors, which upon activation transduce information to the appropriate cellular effector molecules via trimeric G proteins. The G protein-mediated cascades ultimately lead to the highly refined regulation of systems such as sensory perception, cell growth, and hormonal regulation. Transmembrane signaling may be seriously deranged in various pathophysiological conditions. Over the last two decades the major experimental effort of our group has been devoted to better understanding the molecular mechanisms underlying transmembrane signaling regulated by G proteins and to the closely related process of desensitization of hormone response. This review provides general information about the basic principles of G protein-regulated transmembrane signaling as well as about our contribution to the current progress in the field.

Adipose Tissue↗

PubMed2004

[Prophylactic adnexectomy].

OBJECTIVE: Analysis of the issue of prophylactic bilateral salpingo-oophorectomy (BSO): a) during pelvic surgery for benign diagnosis; b) in women with hereditary risk of ovarian cancer. DESIGN: Review article. SETTING: Department of Obstetric and Gynecology, Charles University. METHODS: Critical review of published data. CONCLUSION: During pelvic surgery for benign diagnosis a prophylactic BSO is indicated of the age over 45, in younger women an individual approach is required, considering many aspects, including history of ovarian and breast cancer. Another indication for BSO is an increased risk of familial ovarian cancer. The surgery significantly diminished the risk of epithelial cancer of ovary, fallopian tube, and simultaneously the risk of breast cancer. There is a continuing increased risk of peritoneal cancer following the surgery. Bilateral oophorectomy together with bilateral salpingectomy is recommended. The age limit for surgery is about 35 years after careful consideration of individual risk, reproductive plans, type of mutation and age at malignant disease manifestation in previous generation. Potential alternative for women who do not accept prophylactic surgery is tubal ligation. Screening of risk group or chemoprevention by oral contraceptives are not equivalent alternatives to prophylactic surgery.

Fallopian Tubes↗

PubMed2004

Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation.

Low-density membrane-domain fractions were prepared from S49 lymphoma cells and clone e2m11 of HEK293 cells expressing a large number of thyrotropin-releasing hormone receptor (TRH-R) and G(11)alpha by flotation on sucrose density gradients. The intact cell structure was broken by detergent-extraction, alkaline-treatment or drastic homogenization. Three types of low-density membranes were resolved by two-dimensional electrophoresis and analyzed for G(s)alpha (S49) or G(q)alpha/G11) (e2m11) content. Four individual immunoblot signals of Gsalpha protein were identified in S49 lymphoma cells indicating complete resolution of the long G(s)alpha L+/-ser and short G(s)alpha S+/-ser variants of G(s)alpha. All these were diminished by prolonged agonist (isoprenaline) stimulation. In e2m11-HEK cells, five different immunoblot signals were detected indicating post-translational modification of G proteins of G(q)alpha/G(11)alpha family. The two major spots corresponding to exogenously (over)expressed G(11)alpha and endogenous G(q)alpha were reduced; the minor spots diminished by hormonal stimulation. Parallel analysis by silver staining of the total protein content indicated that no major changes in protein composition occurred under these conditions. Our data thus indicate that agonist-stimulation of target cells results in down-regulation of all different members of G(s) and G(q)/G(11) families. This agonist-specific effect may be demonstrated in crude membrane as well as domain/raft preparations and it is not accompanied by changes in overall protein composition.

Cell Line, Tumor↗

PubMed2004

Immunohistochemical detection of the hMLH1 and hMSH2 proteins in hereditary non-polyposis colon cancer and sporadic colon cancer.

Defects in DNA mismatch repair system are involved in carcinogenesis of sporadic and inherited human cancers. We assessed the feasibility of using immunohistochemistry to detect tumors with DNA mismatch repair deficiency. We analyzed 81 samples (74 colon cancers (CC), 1 colon dysplasia and 6 extracolonic cancers) for hMLH1 and hMSH2 protein expression, microsatellite instability (MSI) and/or mutational analysis. A meta-analysis of the published data on immunohistochemistry of hMLH1/hMSH2 proteins was performed. Sensitivity and specificity of the method was calculated. Twenty four of 29 tumors from hMLH1/hMSH2 mutation carriers and 10 of 13 sporadic high frequency MSI tumors lost one of the proteins. None of the 42 tumors with stable microsatellites or low frequency MSI lost the proteins. Based on literature review of 49 publications on colorectal cancer, hMLH1 immunohistochemistry was able to detect 136 of 154 tumors from hMLH1 germline mutation carriers (the sensitivity of 88.3% [95%CI, 85.8-90.8%]), hMSH2 immunohistochemistry detected 99 of 109 tumors from hMSH2 mutation carriers (the sensitivity of 90.8% [95%CI, 88.5-93.1%]), and hMLH1/hMSH2 immunohistochemistry identified 1262 of 1382 tumors with high-frequency microsatellite instability not correlated with mutational analysis (the sensitivity of 91.3% [95%CI, 90.4-92.2%]). The specificity of the method was 99.4% (95%CI, 99.2-99.6%). In conclusion, immunohistochemistry of hMLH1 and hMSH2 proteins is a useful method to predict the presence of mismatch repair deficiency, although its sensitivity is lower than that of MSI analysis.

Adaptor Proteins, Signal Transducing↗

PubMed2004

[Successful indirect cardiac massage as a cause of thoracic wall instability and respiratory insufficiency].

The authors in their two cases describe unusual complication after successful indirect cardiac massage which was carried out in terrain. Both patients were then transferred to Dept. of gerontology and metabolic care. However the resuscitation was in both cases successful it caused in these two cachectic oseoporotic patients sternal and costal en block fractures. This iatrogenic trauma of thoracic wall showed up in further cause as a major problem. The patients could not have been disconnected from artificial support of ventilation and therefore their thoracic cage had to be surgically stabilized.

Aged↗

PubMed2003

[Dynamic stress echocardiography in asymptomatic patients treated for malignant diseases in childhood].

INTRODUCTION: The authors used echocardiography at rest and dynamic stress echocardiography to assess left ventricular function in asymptomatic patients treated during childhood or adolescence by chemotherapy containing anthracyclines. MATERIAL AND METHODS: 137 patients were examined (81 men, 56 women) aged 16.6 +/- 4.8 years (median 17 years) where at the age of 9.1 +/- 4.8 years (median 9 years) malignant disease was detected and treatment with a cumulative dose of anthracyclines 242 +/- 110 mg/m2 (median 240 mg/m2) was administered. The control group was formed by 30 subjects (14 men, 16 women) aged 19.5 +/- 5.2 years (median 20 years). The echocardiographic examination was made at rest and immediately after a dynamic stress on an ergometer with a load of 25 W/2 mins. RESULTS: In 8% patients (n = 11) a reduction of the fractional shortening (FS) LV < 30% was found. The values of the ejection fraction (EF), the median shortening of the circumferential fibre and endosystolic wall stress, excursion and thickening of the posterior wall of the LV were significantly worse as compared with the group with fractional shortening > or = 30% and the control group. The maximum drop of EF was to 40% and of FS to 20%. The values of the index of the global LV function (according to Teie) were as compared with the control group worse in both sub-groups of patients. No differences were found in the exercise tolerance between groups. Values of the ejection fraction at rest and after a exercise were in the sub-group with FS < 30% significantly lower as compared with the others. The values of the stress increment of EF were elevated in all sub-groups. In none of the subjects the load caused a decline of the EF. CONCLUSIONS: Chemotherapy with anthracyclines leads to a late disorder of several indicators of left ventricular function. Asymptomatic patients with a drop of the EF value to 40% or FS to 20% preserve their load tolerance and contraction reserve of the left ventricle. The finding of a preserved contraction reserve and good exercise tolerance implies a more favourable prognosis of the patient. Echocardiography at rest should be made repeatedly after treatment, in case of a pathological finding a loading test must be indicated to evaluate the contraction reserve and its possible development.

Adolescent↗

PubMed2003

Relationship between K-ras mutation and the expression of p21WAF1/CIP1 and p53 in chronic pancreatitis and pancreatic adenocarcinoma.

Overexpression of p21WAF1/CIP1 was recently described as an early event in the development of pancreatic intraepithelial neoplasia. Since activating K-ras mutations are described in more than 80% of pancreatic cancers and are known to increase intracellular levels of p21WAF1/CIP1 in experimental models, the possible role of activating K-ras mutations in an induction of the p21WAF1/CIP1 expression was investigated in our study. We examined 71 surgical specimens, 29 of chronic pancreatitis and 42 of invasive ductal adenocarcinoma both having a large spectrum of PanIN (pancreatic intraepithelial neoplasia) lesions. Expression of p53 and p21WAF1/CIP1 was examined immunohistochemically and codon 12 K-ras mutational analysis was performed using the very sensitive mutant-enriched PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis. Our study demonstrated the overexpression of p21WAF1/CIP1 as an early event in the development of pancreatic intraepithelial neoplasia in the group of chronic pancreatitis and invasive adenocarcinoma as well. Overexpression of p21WAF1/CIP1 increased progressively from normal ducts through the spectrum of PanIN lesions to invasive carcinomas. The p53 overexpression increased again progressively according to the severity of the lesion and seems to be a later event in the development of pancreatic intraepithelial neoplasia if compared to p21WAF1/CIP1 expression. Our results confirmed also the possible p53 independent p21WAF1/CIP1 expression in some PanIN2, PanIN3 lesions and invasive carcinomas. K-ras mutations were not revealed in samples with only low grade PanIN lesions (PanIN1a and PanIN1b). K-ras mutations were detected in 69,4% adenocarcinomas and in only one case of chronic pancreatitis. Two codon 12 K-ras positive pancreatic carcinomas showed K-ras mutations in the surrounding normal pancreatic tissue. In adenocarcinomas, no statistically significant correlation was found between K-ras mutational status and p21WAF1/CIP1 and p53 expression, respectively. The possible role of activating K-ras mutations in an induction of p21WAF1/CIP1 expression was not confirmed in this study.

Adenocarcinoma↗

PubMed2002

[Minimal residual disease in breast carcinoma].

The incidence of breast cancer continuously increases in developed countries. The introduction of screening methods such as mammography or ultrasound lead to higher proportion of early diagnosed tumors. However, even in early stage tumors occult neoplastic cells can spread to the organism. Such tumor cells are very likely precursors of distant metastases. Using several monoclonal antibodies against epithelial mucins or cytokeratins on the cell surface could be detected one tumor cell among 10(5) or 10(6) of normal bone marrow cells. These cells are not detectable by routine histopathologic exam. More sensitive but also more costly and technically demanding are PCR assays. The sensitivity might reach almost 1:10(7). Prospective clinical trials using immunocytochemistry have shown that the presence of stained cells in bone marrow is clearly associated with shorter disease free survival and overall survival. In the near future we may use the bone marrow examination for the presence of occult tumor cells in order to improve current staging system or as a surrogate marker in the decision-making in regard to adjuvant systemic therapy or in the assessment of efficacy of adjuvant treatment. The review summarizes contemporary knowledge assembled in preclinical and clinical studies.

Bone Marrow↗