Biomedical subjects

J Novotný

Publications and source records attributed to J Novotný.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2002

Medical application of 3-D polymer gel dosemeter evaluated by nuclear magnetic resonance.

A polymer-gel dosemeter, which can be evaluated by nuclear magnetic resonance (NMR), was prepared and then a few samples were homogeneously irradiated by a Leksell gamma knife using an 18 mm collimator (60Co gamma photons) to obtain a calibration curve (NMR 1/T2 response to absorbed dose). To measure dose distribution from the Leksell gamma knife, a testing flask tilled with the gel was fixed in the head phantom and then irradiated based on a calculated treatment plan. Evaluation of dosemeters was performed on a Siemens EXPERT 1T NMR scanner. Dose profiles in X, Y and Z coordinates through the ellipsoidal shape of the dose distribution were obtained to compare experimental results from the irradiated phantom with the treatment planning system calculations. The use of a polymer-gel dosemeter for a verification of stereotactic procedures has some unique advantages which can be summarised as follows: (1) the dosemeter itself is tissue equivalent, (2) three-dimensional dose distributions can be measured, (3) the dosemeter allows patient's procedures to be simulated without any limitations.

Calibration↗

PubMed2002

In vivo thermoluminescence dosimetry for total body irradiation.

An improvement in the clinical results obtained using total body irradiation (TBI) with photon beams requires precise TBI treatment planning, reproducible irradiation, precise in vivo dosimetry, accurate documentation and careful evaluation. In vivo dosimetry using LiF Harshaw TLD-100 chips was used during the TBI treatments performed in our department. The results of in vivo thermoluminescence dosimetry (TLD) show that using TLD measurements and interactive adjustment of some treatment parameters based on these measurements, like monitor unit calculations, lung shielding thickness and patient positioning, it is possible to achieve high precision in absorbed dose delivery (less than 0.5%) as well as in homogeneity of irradiation (less than 6%).

Calibration↗

PubMed2002

[Early surgical stabilization of the thorax].

Patients with non-penetrating chest trauma are encountered with increasing frequency. Car crash is the main cause of blunt chest trauma. Despite their nature these lesions may be life-threatening. The mortality rate of chest injuries varies from 20 to 50%. In the last 3 years 86 patients with blunt chest injuries were treated in our institution. 24 patients underwent surgical repair. We compared the outcome of surgical and conservative treatment. Early diagnosis and proper treatment reduce morbidity and mortality.

Adult↗

PubMed2002

[Apoptosis and its importance in the development and therapy of tumors (review)].

This review focuses on apoptosis and its regulation as a tool of principal control mechanism of tissue homeostasis. Defects in regulation of apoptosis contribute to a various pathological processes, including tumor development, chronic inflammatory diseases, immunological disorders and many others. Apoptosis influences sensitivity to radiotherapy and chemotherapy of tumours. Microscopically the apoptosis is characterized by morphological changes, which result in the formation of apoptotic bodies. Apoptosis is an active process, which require synthesis and activation of a set of the specific cellular proteins. Among them, the key role belongs to the family of cystein proteases--caspases activated either through the death receptors or via activation steps starting with the release of a mitochondrial cytochrome c. Activation of caspases promotes the activation of downstream effectors leading to the cleavage of target cellular proteins and genomic DNA. The members of Bcl-2 family and p53 are- the others important proteins influencing the regulation of apoptosis. Enhancing of our knowledge about apoptosis and its mechanisms highly improves the rationale for diagnostics and therapy in oncology.

Apoptosis↗

PubMed2002

[Complications of axillary dissection in breast carcinoma ].

OBJECTIVE: The objective of the work was to evaluate the incidence and type of postoperative complications after radical exenteration of the axilla in conjunction with an implemented surgical operation. DESIGN: Retrospective clinical study. SETTING: Gynaecological and Obstetric Clinic, First Medical Faculty Charles University and General Faculty Hospital Prague, Apolinárská 18, Prague. METHOD: The authors made a retrospective analysis of postoperative complications in 116 selected patients, who underwent partial breast surgery or ablation of the breast with dissection of the axilla at the Gynaecological and Obstetric Clinic, First Medical Faculty Charles University and General Faculty Hospital in Prague in 1994-2000 on account of breast cancer stage I and II according to FIGO. The group comprised patients where radiotherapy or chemotherapy of the axilla was not used. The patients were at least 12 months after operation without signs of locoregional relapse of the disease and in the dissected axillary tissue at least 10 lymph nodes were found. The operations were implemented by nine different surgeons. Early (infection, seroma, haematoma) as well as late (oedema, paraesthesia, stiffness, pain, weakness of the upper extremity) complications were also evaluated. The authors compared the incidence of complaints in relation to age, the number of dissected nodes and extent of the breast surgery. The statistical significance of the phenomena was evaluated by Fisher's exact test. RESULTS: At least one complication was recorded in 65% of the patients. In early complications (haematoma, infection, seroma) neither the correlation with the patient's age nor with the number of removed nodes was significant. There was a statistically significant relationship (P < 0.05) between the incidence of infection and the extent of the breast surgery which probably was associated with the wound area. As to late complications (oedema, paraesthesia, stiffness, pain and weakness of the upper extremity) a significant relationship was found with lower painfulness in patients above 55 years (P < 0.05) and lower sensation of weakness and paraesthesias in patients with partial breast operations (P < 0.05). The more frequent complaints of younger patients were probably due to their greater everyday physical activity as compared with older women. The higher number of subjective complications in patients after ablation of the breast is explained not only by the size of the wound area but also by psychosocial reasons. CONCLUSION: Dissection of the axilla is part of standard surgical treatment of breast cancer. The surgical operation without radio- or chemotherapy is associated in 65% cases with long-term morbidity of the patients. With regard to the shift of diagnosis of breast cancer to earlier stages it is important to seek a less invasive staging method which will reduce the patient's morbidity. The sentinel node biopsy method seems perspective.

Aged↗

PubMed2002

[Diagnostic possibilities of late cardiotoxic sequelae of chemotherapy with anthracyclines].

Anthracyclines areamong the most frequently used cytostatics in the treatment of haematological malignities and some solid tumours in childhood and adult age. They affect cellular proliferation in several ways. One of them is the formation of semiquinone radicals which form with oxygen toxic peroxides which damage the myocyte and lead to cardiotoxicity. Cardiotoxicity of anthracyclines has become a clinical problem as it restricts the administered dose of the cytostatic and has become particularly urgent after discovery of the late toxicity which appears some years after termination of anti-tumourous treatment. Damage of the left ventricle is usually characterized by partial reversible contractile dysfunction (early damage) or progressing contractile dysfunction (late damage). The diagnosis of cardiotoxicity is important during the period of treatment but in particular after completed chemotherapy. The application of diagnostic methods before and in the course of chemotherapy is indicated when large doses of anthracyclines will be administered or when in the patient risk factors cumulate or if he developed signs of cardiotoxicity. The use of diagnostic methods after termination of treatment is valuable for early detection of late cardiotoxicity for timing of further diagnostic methods currently used in cardiology. In the routine diagnosis the authors prefer follow up of the left ventricle by assessment of the ejection fraction by echocardiography or by radionuclide examination. In paediatrics we follow up indicators of systolic left ventricular function in relation to changes of the after load. The authors present also a review of other diagnostic methods and procedures which may prove useful in the diagnosis of cardiotoxicity of anthracyclines.

Anthracyclines↗

PubMed2001

Maturation of rat brain is accompanied by differential expression of the long and short splice variants of G(s)alpha protein: identification of cytosolic forms of G(s)alpha.

Distribution of the alpha subunit of the stimulatory G protein (G(s)alpha) was analyzed in membrane and cytosolic (supernatant 200 000 g) fractions from rat cortex, thalamus and hippocampus during the course of post-natal development. In parallel, changes in beta-adrenoceptor density and adenylyl cyclase activity were determined. Long (G(s)alphaL) and short (G(s)alphaS) variants of G(s)alpha were assessed by immunoblotting using specific polyclonal antisera reacting with both G(s)alpha isoforms. Post-natal development was associated with an increase in the total amount of brain G(s)alpha. G(s)alphaL was the dominant isoform of G(s)alpha in the membrane fractions of all studied brain regions and its amount increased markedly between post-natal day (PD) 1 and 90. The level of membrane-bound G(s)alphaS also elevated during post-natal development, but more pronounced changes were found in cytosolic G(s)alphaS. Although only a small amount of G(s)alphaS (much smaller than G(s)alphaL) was detected among soluble proteins shortly after birth, G(s)alphaS prevailed over G(s)alphaL at PD90. The G(s)alphaL/G(s)alphaS ratio decreased, respectively, from 3.2 to 1.2 and from 5.0 to 1.5 in the membrane fractions of cortex and hippocampus, but remained almost constant in thalamus between PD1 and 90. More dramatic changes were found in the cytosolic fractions of all studied brain regions: the G(s)alphaL/G(s)alphaS ratio decreased sharply in cortex (from 14.1 to 0.9), hippocampus (from 3.7 to 0.8), and also in thalamus (from 9.5 to 0.5). These results demonstrate that the membrane-cytosol balance of G(s)alpha proteins alters dramatically during the course of brain development. Both G(s)alphaL and G(s)alphaS were expressed in a region- and age-specific manner, which suggests different roles in the maturation of the brain tissue. A cyc(-) reconstitutive assay of cytosolic G(s)alpha indicated that only approximately 20% of this protein was functional, compared with membrane-bound G(s)alpha, and its ability to reconstitute adenylyl cyclase activity increased during the course of maturation. The number of beta-adrenoceptors increased sharply during early post-natal development but only slightly in adulthood, and both GTP- and isoproterenol-stimulated adenylate cyclase activity reached peak values around PD12.

Adenylyl Cyclases↗

PubMed2001

Prospective study of fungaemia in a single cancer institution over a 10-y period: aetiology, risk factors, consumption of antifungals and outcome in 140 patients.

Over a 10-y period (1989-99) we prospectively evaluated all patients with fungaemia among 16,555 admissions (21,004 blood cultures) at a national cancer referral institution in the Slovak Republic. A prospective protocol was completed on 140 patients with fungaemia, which was then analysed in terms of aetiology, clinical characteristics, potential risk factors and outcome. The most frequently isolated organism was C. albicans, in 75 patients (52.9%), followed by non-albicans Candida spp. in 45 patients (32.1%). Non-Candida spp. yeasts represented 16 episodes in 16 patients (11.4%). Moulds caused 4 episodes in 4 patients (3.6% of all fungaemias) and all were caused by Fusarium spp. Mucositis (p = 0.025), > or = 3 positive blood cultures (p = 0.02), acute leukaemia (p = 0.00001), neutropenia (p = 0.0015), quinolone prophylaxis (p < 0.000005) and breakthrough fungaemia (p = 0.004) during prophylaxis with fluconazole (p = 0.03) and itraconazole (p = 0.005) were significantly more associated with non-Candida than C. albicans spp. Furthermore, attributable mortality was higher in the subgroup of non-Candida than C. albicans spp. (50.0 vs. 18.7%, p < 0.02). The only independent risk factor for inferior outcome was antifungal therapy of < 10 d duration (odds ratio 2.1, 95% confidence interval, p < 0.001). Aetiology, neutropenia and mucositis were not independent risk factors for higher mortality in multivariate analysis; however, they were risk factors for inferior outcome in univariate analysis (p < 0.05-0.005).

Adolescent↗

PubMed2001

Prognostic significance of c-erbB-2 gene expression in pancreatic cancer patients.

Molecular methods tend to belong to the standard armamentarium of modern pathology. In some instances, these methods are able to identify nosological entities with better accuracy than conventional technique. These methods give useful complementary information to choose appropriate therapeutic strategy. C-erbB-2 overexpression in pancreatic cancer vary widely between 17 to 82%. C-erbB-2 gene is perspective target of anticancer therapies. 57 histologically confirmed tumors (51 pancreatic adenocarcinoma, 5 pancreatic neuroendocrine tumors and 1 carcinoma of Vater's ampullae) were analyzed for the presence of c-erbB-2 expression by immunohistochemistry. Correlation with time from initial symptoms until diagnosis, tumor size and TNM stage at diagnosis, tumor grade, type of operation and overall survival were investigated. C-erbB-2 overexpression was detected in 19.6% samples of pancreatic adenocarcinoma and in one case of Vater's ampullae carcinoma. C-erbB-2 overexpression was found in two of four insulinomas. Univariate statistical correlation stage between c-erbB-2 overexpression and time from initial symptoms until diagnosis, tumor size and TNM at diagnosis, tumor grade, type of operation and overall survival did not reach statistical significans in any parameter studied. C-erbB-2 oncogene was not found to be prognostic factor in pancreatic cancer. Its value to predict therapeutical response remains to be determined in prospective clinical trials.

Adenocarcinoma↗

PubMed2001

[Pulmonary "tumorlet" as a neoplastic condition?].

A 66-year-old woman, non-smoker, with a diffuse bilateral pulmonary interstitial involvement caused by multiple carcinoid tumorlets associated with a diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The process has developed during the last two years of the patient's life. There were no pathologic changes in the remnant pulmonary parenchyma. Moreover, the minute typical carcinoid (5.2 mm) was encountered after extensive pulmonary tissue examination. The spectrum of DIPNECH, multiple tumorlets, and typical carcinoid tumor demonstrates a possible neoplastic character of the pulmonary tumorlet.

Aged↗

PubMed2000

[Radiosurgical treatment of hypophyseal adenomas with the gamma knife: results in a group of 163 patients during a 5-year period].

BACKGROUND: Gamma knife radiosurgery of pituitary adenomas is considered to be very perspective. It can be a very useful complement of traditional microsurgery, pharmacotherapy or fractionated radiotherapy which are seldom a sufficient treatment on their own. The modern radiosurgery does not offer the experience representative enough in this indication. We can offer results of medium long follow-up for tumor growth and hormonal hypersecretion of pituitary adenomas in a relatively large series of patients. METHODS AND RESULTS: We have analyzed a group of 163 patients with pituitary adenoma treated with gamma knife during 5 years and followed 12-60 months, median 24 months after irradiation. An antiproliferative effect has been achieved in 1-2 years using the minimal dose to the margin 16-35 Gy, median 20 Gy in all our patients who were controlled by MRI (n = 126 patients). One half of these adenomas evidently decreased their size. Our effective antiproliferative dose was safe for the surrounding structures. The hormonal normalization has been achieved at 50.4% from 133 hypersecreting adenomas (39/91 = 43% of acromegalics, 11/13 = 85% of patients with Cushing's disease, 2/9 = 22% of patients with Nelson's syndrome, 11/18 = 61% of prolactinomas). The median latency was 12 months. The minimal dose to the margin was 10-45 Gy, median 35 Gy. Rare side effects were provoked only by increasing the dose to influence the hypersecretion-the development of partial hypopituitarism in 3.1% of patients, the panhypopituitarism in 0.6% of patient and there was 1 hemianopic visual field defect (0.6%). CONCLUSIONS: Radiosurgery by gamma knife has a similar value for pituitary adenomas as microsurgery has with different distribution of advantages and drawbacks. This makes it suitable for the combined treatment where pharmacotherapy has its place under special conditions. Fractionated radiotherapy has now a marginal importance.

Adenoma↗

PubMed2000

Differentiation of cultured brown adipocytes is associated with a selective increase in the short variant of g(s)alpha protein. Evidence for higher functional activity of g(s)alphaS.

In order to examine whether the differentiation process in brown adipocytes cultivated in primary culture is associated with substantial alterations in the complement of G proteins, the levels of these proteins were investigated with immuno-electrophoretic techniques in membrane preparations from proliferating and differentiated cultured mouse brown adipocytes. We observed that differentiation was associated with a dramatic (more than threefold) increase in the short variant of G(s)alpha protein (G(s)alphaS). The long variant of G(s)alpha (G(s)alphaL), as well as G(i)1alpha, G(i)2alpha, G(q)alpha, G(11)alpha and Gbeta subunit proteins remained unchanged whereas G(i)3alpha protein was decreased. These changes were accompanied by marked increase in isoprenaline-, forskolin- as well as manganese-stimulated adenylyl cyclase. Thus, the marked increase in beta-adrenergic responsiveness of fully differentiated confluent brown adipocytes (day 8-9), as compared with that of proliferating undifferentiated cells of 'fibroblast phenotype' (day 3-4), is associated with a significant increase in the relative proportion between the short and long variants of G(s)alpha (the G(s)alphaS/G(s)alphaL ratio) along with a decrease in G(i)3alpha protein. These data also suggest that the short variant of G(s)alpha exhibits higher functional activity than the long variant of this G protein.

Adenylyl Cyclases↗

PubMed2000

Solitary brain metastases treated with the Leksell gamma knife: prognostic factors for patients.

PURPOSE: To analyze treatment results, complications, prognostic factors and their statistical significance in surviving patients treated with the Leksell gamma knife (LGK) for solitary brain metastases. MATERIALS AND METHODS: Between 1992-1998, 237 patients were treated with solitary brain metastasis (SBM). The histological subtypes were as follows: 101 patients (42.6%) non small-cell lung cancer, 42 (17.7%) renal cell carcinoma, 36 (15.2%) breast carcinoma, 30 (12.7%) colorectal carcinomas and 28 (11.8%) melanoma. RESULTS: A complete or partial regression was observed in 193 (81.4%) patients, cessation of growth activity in 32 (13.5%) and local progression in 12 (5.1%). Local recurrence was observed in nine (4.7%) of 193 patients with complete or partial regression. Acute toxicity appeared in 24 (10%) patients (score 3.4), late complications (score 3.4) were observed in 13 patients (5.5%). Out of 237 patients, 182 patients died with a median survival of 6 months and 55 patients are still alive with a median survival 12 months and with a minimal follow up period of 10 months. The significant prognostic factors for longer survival in these series of patients were: Karnofsky performance status (70% or more), the extent of extra-cerebral disease (no extra-cerebral disease), pretreatment neurological symptoms neurological functional class (NFC 1), histology (renal cell and breast carcinomas) and the dose to the planning target volume (20 Gy and higher). CONCLUSIONS: Radiosurgery provides an effective local control for 90% of treated patients with low morbidity. Several significant prognostic factors were detected for patients' survival. These factors can help to predict better patients' survival after the LGK treatment.

Adult↗

PubMed2000

High prevalence of Helicobacter heilmannii-associated gastritis in a small, predominantly rural area: further evidence in support of a zoonosis?

BACKGROUND: Primary hosts of Helicobacter heilmannii are domestic animals--cats, dogs and pigs, but rarely is it detected in gastric biopsies from humans. We found H. heilmannii in gastric biopsies obtained from patients living in a predominantly rural area. METHODS: We evaluated geographic and demographic data from the area and calculated both the total prevalence and the prevalence in each community in this area. Chi-squared test and exploratory data analysis were used for statistical evaluation. Histologic and clinical data were recorded. RESULTS: Forty-three communities, mostly rural, were identified in the area, the size of which is about 200 km2. H. heilmannii was detected in 33 patients (prevalence 2%) living in 20 communities. The prevalence of H. heilmannii statistically significantly varied in those communities from 0.06%-1.1%. It was possible to infer that there is a negative correlation between prevalence and community size. Chronic active gastritis was diagnosed in all patients. The active inflammation became inactive after eradication of H. heilmannii via common anti-Helicobacter therapy. CONCLUSION: A high prevalence of H. heilmannii-associated gastritis in a small, predominantly rural area and statistically significant differences in prevalence from one community to the next, i.e. highest in the smallest village and lowest in a small town with a rather urban lifestyle, were found. In our opinion, these prevalence rates may be a consequence of transmission of the infection from domestic animals, because animal-human contact is generally more common in villages than in towns.

Animals↗

PubMed1999

Thyrotropin-releasing hormone-induced depletion of G(q)alpha/G(11)alpha proteins from detergent-insensitive membrane domains.

The role of detergent-insensitive membrane domains (DIMs) in desensitisation of the G protein-coupled receptor-mediated hormone response was studied in clone E2M11 of HEK293 cells which stably express high levels of both thyrotropin-releasing hormone (TRH) receptors and G(11)alpha G protein. DIMs were prepared by flotation in equilibrium sucrose density gradients and characterised by a panel of membrane markers representing peripheral, glycosylphosphatidylinositol-bound as well as integral membrane proteins (caveolin, CD29, CD55, CD59, CD147, the alpha subunit of Na, K-ATPase) and enzyme activities (alkaline phosphatase, adenylyl cyclase). Caveolin-containing DIMs represented only a small fraction of the overall pool of G(q)alpha/G(11)alpha-rich domains. Prolonged stimulation of E2M11 cells with TRH resulted in dramatic depletion of G(q)alpha/G(11)alpha from all DIMs, which was paralleled by a concomitant G(q)alpha/G(11)alpha increase in the high-density gradient fractions containing the bulk-phase membrane constituents soluble in 1% Triton X-100. Distribution of membrane markers was unchanged under these conditions. Membrane domains thus represent a substantial structural determinant of the G protein pool relevant to desensitisation of hormone action.

Adenylyl Cyclases↗

PubMed1999

Overexpression of the G protein G11alpha prevents desensitization of Ca2+ response to thyrotropin-releasing hormone.

Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing both thyrotropin-releasing hormone (TRH) receptors and G11alpha protein in high amounts were used to analyze the desensitization phenomenon of the Ca2+-mobilizing pathway. Quite unexpectedly, we did not observe any significant desensitization of the [Ca2+]i response to TRH in these cells after repeated or prolonged incubation with the hormone (up to 5 h). Under the same conditions, the TRH-induced [Ca2+]i response was completely desensitized in the parent cell line (293-E2 cels) expressing TRH receptors alone. In both cell lines, inositol phosphate response was desensitized after TRH exposure, although basal levels of inositol phospates in TRH-pretreated cells were much higher than in "naive" TRH-unexposed cells. These data suggest a significant role of the G protein G11alpha in desensitization of the Ca2+-mobilizing pathway occuring after repeated or long-term exposure of target cells to TRH-receptor agonists.

Animals↗

PubMed1999

The role of Gamma Knife radiosurgery in arteriovenous malformation with aneurysms.

A review of 217 patients treated with Gamma knife radiosurgery (GKRS), at Hospital Na Homolce, Prague, between October 1992 and January 1998 for arteriovenous malformation (AVM) is presented. Forty-one patients (18.9%) with an AVM and associated aneurysm are the subjects of special interest for this study. The nidus volume in the presence of an aneurysm lying close to the nidus or within it was significantly larger than the nidus volume in cases where the AVMs had no associated aneurysm, suggesting that an increased flow in a larger AVM may be an important factor for aneurysm formation. The association of an arterial aneurysm with an AVM significantly increased the chance of hemorrhage when compared to the group with AVM and no aneurysm. Ten patients out of 14, who had an aneurysm close to or within the nidus, showed a complete obliteration of their AVM and aneurysm, although the latter was not always included within the irradiated volume. Thus, this study indicates that radiosurgery alone could be the method of choice for the treatment of a combination of AVM and aneurysm, if the aneurysm is close to or within the nidus.

Adolescent↗