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G Nemeth

Publications and source records attributed to G Nemeth.

At least 19 recordsLinked to original sources
PubMed2006

A comparison of accommodation amplitudes in pseudophakic eyes measured with three different methods.

PURPOSE: To compare the accommodative amplitudes with three different methods in pseudophakic eyes with different types of intraocular lenses (IOLs). METHODS: Fifty-one pseudophakic eyes of 44 patients (age: 72.02+/-8.53 years) were studied. One of two different types of IOL were implanted (N=30, three-piece Alcon Acrysof MA60AC and N=21, one-piece Alcon Acrysof SA60AT) in-the-bag after standard phacoemulsification. The time of the examinations was 13.85+/-7.35 months postoperatively. We measured the amplitude of accommodation with three different methods: (1) subjective minus-lenses-to-blur method; (2) a new optical device (ACMaster, Carl Zeiss, Jena, Germany) using partial coherence interference (PCI) technique under physiological stimulus; and (3) objective anterior chamber depth measuring with a standard A-scan ultrasonic device (Ultrascan Imaging System, Alcon Laboratories, Forth Worth, TX, USA) before and after pharmacological relaxation of ciliary muscle. RESULTS: We measured -0.83+/-0.63 D amplitude of accommodation with subjective minus-lenses-to-blur method. The IOL position did not change significantly during physiological accommodation effort measured with PCI method (-0.026+/-0.134 mm). The change in the IOLs position between near fixating and after ciliary muscle relaxation was -0.18+/-0.28 mm measured with ultrasound. There were no significant differences between values of one-piece and three-piece IOL groups. CONCLUSION: The amplitude of accommodation measured by subjective and objective methods are different and are not comparable with each other. We did not observe any difference between values of examined two types of IOLs.

Accommodation, Ocular↗
PubMed2004

Brachytherapy of vestibular schwannomas: report of three cases.

OBJECTIVE: Gamma knife and multileaf collimator LINAC have recently gained notoriety in the treatment of vestibular schwannomas. Without the use of gamma knife or LINAC, we have successfully pursued the 125-iodine interstitial irradiation of three vestibular schwannomas. CASE REPORT: Up to March 2004, there was a 57 and 45 month follow-up period in two cases. One patient died of heart insufficiency 15 months after the brachytherapy. At the end of the follow-up period audiometric examinations revealed slight improvements of hearing in patients 1 and 2. In patient 1, the tumor volume measured was 4.06 mL on the control CT indicating a 40 % shrinkage in comparison to the 6.74 mL target volume at the brachytherapy. In patient 2, the tumor volume measured on the control MRI was 6.64 mL, indicating a 42 % shrinkage of the 11.45 mL target volume at the time of brachytherapy. Eleven months after the brachytherapy in patient 3 we found 10 % tumor shrinkage, a post-irradiation cyst developed inside the tumor and reached up to 35 % of the tumor volume. INTERVENTION: In the treatment of three vestibular schwannomas we have used CT and image-fusion guided 125-iodine stereotactic brachytherapy. CONCLUSION: Due to financial considerations, gamma knife and LINAC are not available for many countries and neurosurgical institutes. In the absence of the above-mentioned radiosurgical methods, we have shown brachytherapy as a new alternative and solution in the treatment of the three patients studied with vestibular schwannoma.

Aged↗
PubMed2001

NMR characterization of a novel bile acid sequestrant, DMP 504.

DMP 504, a potential bile acid sequestrant for the treatment of hypercholesterolemia, is a highly insoluble, cross-linked polymer which does not lend itself to ordinary means of characterization used for drug substances in the pharmaceutical industry. Therefore, alternative characterization techniques have been sought. As part of an effort into extensive characterization of DMP 504 drug substance, nuclear magnetic resonance (NMR) was employed to provide insight into details of the DMP 504 polymer structure. The primary motivation for determining the structure of the polymer chain is to relate the DMP 504 structure to its performance properties as a bile acid sequestrant. Characterization of the polymer chain and understanding of the structural basis of its properties is essential in optimizing and controlling the manufacture of reproducible drug substance. NMR has proven a versatile tool for the description of polymer structure and dynamics because of the wide range of nuclear interactions affecting the NMR signal. This allows the design of experiments to elicit information about specific polymer interactions or properties. The methods of sample preparation utilized to obtain NMR spectra of the insoluble polymer, as well as a discussion and comparison of results for the characterization of DMP 504 obtained using several different NMR techniques will be presented.

Bile Acids and Salts↗
PubMed2001

The role of STIR MRI sequence in the evaluation of the breast following conservative surgery and radiotherapy.

The purpose of the study was to define the value of fat suppressed STIR sequence in the MRI of the conserved breast. To our knowledge, this study is the first clinical evaluation of STIR sequence in post-therapy conditions. Forty patients with early (T1-2, N0-1) invasive breast cancer underwent conservative surgery and postoperative radiotherapy. Routine follow-up examinations, including physical examination and mammography were supplemented with breast MRI in all cases 6-166 months (mean 27.6) after initial treatments. Three patients had bilateral cancer. Including follow-up (9 patients) MRI examinations, altogether 53 MRIs were available for analysis. An 0.5 T MRI (Elscint, Haifa, Israel) was used with double breast coil. Axial T1 and T2 weighted spin echo, STIR and 3D gradient echo dynamic sequences were performed. Pre- and postcontrast slices underwent serial subtraction. Twenty-eight circumscribed lesions were identified. All were well visualised on STIR sequence, regardless of histologic nature of lesions. One low grade DCIS was not detected by any sequence. Differential diagnosis between benign and malignant lesions was not possible by STIR sequence alone. STIR sequence was found to be more sensitive in the detection of treatment related breast edema and fluid collection, than T2 SE (spin-echo) sequence. Even the patients who were not good candidates for subtracted contrast enhanced dynamic studies - because of motion artefacts - could have been examined with satisfactory results. STIR is a very sensitive sequence for depicting circumscribed lesions and post-therapy complications, but not suitable for differentiation. It is a useful tool in the follow-up of patients with conserved breast subjected to radiotherapy.

Breast↗
PubMed2000

Characterization of novel glutathione adducts of a non-nucleoside reverse transcriptase inhibitor, (S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-3, 4-dihydro-2(1H)-quinazolinone (DPC 961), in rats. Possible formation of an oxirene metabolic intermediate from a disubstituted alkyne.

The postulated formation of oxirene-derived metabolites from rats treated with a disubstituted alkyne, (S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-3, 4-dihydro-2(1H)-quinazolinone (DPC 961), is described. The reactivity of this postulated oxirene intermediate led to the formation of novel glutathione adducts whose structures were confirmed by LC/MS and by two-dimensional NMR experiments. These metabolites were either excreted in rat bile or degraded to mercapturic acid conjugates and eliminated in urine. To demonstrate the oxidation of the triple bond, an analogue of DPC 961 was synthesized, whereby the two carbons of the alkyne moiety were replaced with (13)C stable isotope labels. Rats were orally administered [(13)C]DPC 961 and glutathione adducts isolated from bile. The presence of an oxygen atom on one of the (13)C labels of the alkyne was demonstrated unequivocally by NMR experiments. Administration of (14)C-labeled DPC 961 showed that biliary elimination was the major route of excretion with the 8-OH glucuronide conjugate (M1) accounting for greater than 90% of the eliminated radioactivity. On the basis of radiochemical profiling, the glutathione-derived metabolites were minor in comparison to the glucuronide conjugate. Studies with cDNA-expressed rat enzymes, polyclonal antibodies, and chemical inhibitors pointed to the involvement of P450 3A1 and P450 1A2 in the formation of the postulated oxirene intermediate. The proposed mechanism shown in Scheme 1 begins with P450-catalyzed formation of an oxirene, rearrangement to a reactive cyclobutenyl ketone, and a 1,4-Michael addition with endogenous glutathione to produce two isomeric adducts, GS-1 and GS-2. The glutathione adducts were subsequently catabolized via the mercapturic acid pathway to cysteinylglycine, cysteine, and N-acetylcysteine adducts. The transient existence of the alpha,beta-unsaturated cyclobutenyl ketone was demonstrated by incubating the glutathione adduct in the presence of N-acetylcysteine and monitoring the formation of N-acetylcysteine adducts by LC/MS. Epimerization of GS-1 to GS-2 was also observed when N-acetylcysteine was omitted from the incubation.

Animals↗
PubMed2000

Mass spectrometric and NMR characterization of metabolites of roxifiban, a potent and selective antagonist of the platelet glycoprotein IIb/IIIa receptor.

1. The methyl ester prodrug roxifiban is an orally active, potent and selective antagonist of the platelet glycoprotein GPIIb/IIIa receptor and is being developed for the prevention and treatment of arterial thrombosis. 2. Roxifiban was rapidly hydrolyzed to the zwitterion XV459 in vivo and by liver slices from the rat, mouse and human and by intestinal cores from dog. XV459 was metabolized to only a small extent in vitro and in vivo. 3. Studies with rat and dog given radiolabelled roxifiban showed limited oral absorption with the majority of the radiolabel being excreted in faeces. After i.v. doses of 14C-roxifiban, most of the radioactivity was recovered in the urine of rat whereas the dog excreted significant amounts of radioactivity in bile and urine. 4. XV459 could be metabolized extrahepatically by dog gut flora to produce an isoxazoline ring-opened metabolite. In vitro hepatic metabolism of XV459 was mainly by hydroxylation at the prochiral and chiral centres of the isoxazoline ring. These hydroxylated metabolites were not detected in the urine and plasma of human volunteers administered roxifiban. 5. Initial LC/MS identification of metabolites was achieved by dosing the rat with an equimolar mixture of d0:d4 roxifiban and detecting isotopic clusters of pseudomolecular ions. Unequivocal characterization of these metabolites was achieved by LC/MS, LC/NMR and high-field NMR techniques using synthetic standards of the metabolites. 6. The synthesis of one hydroxylated metabolite enabled the assignment of the correct stereochemistry of the substituted hydroxyl group on the isoxazoline ring.

Amidines↗
PubMed2000

Mitochondrial uncoupling protein 2 (UCP2) in the nonhuman primate brain and pituitary.

Energy dissipating mechanisms and their regulatory components represent key elements of metabolism and may offer novel targets in the treatment of metabolic disorders, such as obesity and diabetes. Recent studies have shown that a mitochondrial uncoupling protein (UCP2), which uncouples mitochondrial oxidation from phosphorylation, is expressed in the rodent brain by neurons that are known to regulate autonomic, metabolic, and endocrine processes. To help establish the relevance of these rodent data to primate physiology, we now examined UCP2 messenger RNA and peptide expressions in the brain and pituitary gland of nonhuman primates. In situ hybridization histochemistry showed that UCP2 messenger RNA is expressed in the paraventricular, supraoptic, suprachiasmatic, and arcuate nuclei of the primate hypothalamus and also in the anterior lobe of the pituitary gland. Immunocytochemistry revealed abundant UCP2 expression in cell bodies and axonal processes in the aforementioned nuclei as well as in other hypothalamic and brain stem regions and all parts of the pituitary gland. In the hypothalamus, UCP2 was coexpressed with neuropeptide Y, CRH, oxytocin, and vasopressin. In the pituitary, vasopressin and oxytocin-producing axonal processes in the posterior lobe and POMC cells in the intermediate and anterior lobes expressed UCP2. On the other hand, none of the GH-producing cells of the anterior pituitary was found to produce UCP2. The abundance and distribution pattern of UCP2 in the primate brain and pituitary suggest that this protein is evolutionary conserved and may relate to central autonomic, endocrine and metabolic regulation.

Animals↗
PubMed1999

Incidence and time of occurrence of regional recurrence in stage I-II breast cancer: value of adjuvant irradiation.

PURPOSE: The value of adjuvant radiation therapy (RT) of the axilla and supraclavicular fossa is controversial in early-stage breast cancer. This retrospective study was undertaken to identify pathological risk factors that would predict which subsets of patients would benefit from regional nodal irradiation (RNI). METHODS AND MATERIALS: A total of 1309 women with Stage I/II breast cancer underwent full axillary dissection and either mastectomy (n = 894) or breast-conserving surgery (n = 415). Of these, 712 patients received RNI. The median axilla/supraclavicular fossa dose was 50 Gy. RESULTS: The 10-year actuarial rate of axillary failure (AXF) was 0. 5% in N0 and 2.8% in N1 patients (p 5, also correlated with AXF; the respective rate was 4.3% vs. 1.2% (p = 0.0142). Neither the incidence of AXF nor the time to AXF was affected significantly by the use of RNI, but in N1 patients with retrieved nodes < or = 5, the rate of AXF was 8.3% without RNI vs. 0% with RNI (p = 0.2340). The 10-year actuarial rate of supraclavicular failure (SCF) was 1.2% in N0 and 6.3% in N1 patients (p = 0.0000). SCF was also associated with the extent of nodal involvement (p = 0.0031). The incidence of SCF was not significantly affected by the use of RNI. However, when the results of N1bii and N1biv patients were evaluated as a single group, the effect of RNI was significant (p = 0.0358). The rates of SCF without RNI were high in patients with N1bii or N1biv stage: 10% and 37.5% and, with RNI, 3.2% and 18.2%, respectively. These findings were reinforced by the various combinations of T- and N1-stage. The mean time to SCF was 53.6 months in the irradiated and 24.9 months in the nonirradiated patients (p = 0.0007). CONCLUSIONS: After a complete axillary dissection, only N1 patients with retrieved nodes < or = 5 may be considered for axillary RT. Elective supraclavicular RT is suggested for patients with N1bii or N1biv stage. Supraclavicular irradiation decreases the incidence and delays the appearance of SCF.

Adult↗
PubMed1999

Liquid chromatography/mass spectrometry and high-field nuclear magnetic resonance characterization of novel mixed diconjugates of the non-nucleoside human immunodeficiency virus-1 reverse transcriptase inhibitor, efavirenz.

Efavirenz (Sustiva) is a potent and specific inhibitor of the HIV-1 reverse transcriptase and is approved for the treatment of HIV infection. The metabolism of efavirenz in different species has been described previously. Efavirenz is primarily metabolized in rats to the glucuronide conjugate of 8-OH efavirenz. Electrospray ionization-liquid chromatography/mass spectrometry analyses of bile samples from rats dosed with either efavirenz or with 8-OH efavirenz revealed three polar metabolites, M9, M12, and M13, with pseudomolecular ions [M-H](-) at m/z 733, 602, and 749, respectively. The characteristic mass spectral fragmentation patterns obtained for metabolites M9 and M13 suggested that these were glutathione-sulfate diconjugates, and the presence of a glutathione moiety in metabolite M9 was confirmed by liquid chromatograpy/nuclear magnetic resonance (NMR) analysis of bile extracts. Metabolite M12 was characterized by liquid chromatography/mass spectrometry as a glucuronide-sulfate diconjugate. Unambiguous structures of M9, M12, and M13 were obtained from one-dimensional proton and carbon NMR as well as proton-proton (correlated spectroscopy, two-dimensional shift correlation), proton-carbon heteronuclear multiple quantum correlation, and long-range proton-carbon (heteronuclear multiple bond correlation) correlated two-dimensional NMR analyses of metabolites isolated from rat bile. The mass spectral and NMR analyses of M10, which was isolated from rat urine, suggested a cysteinylglycine-sulfate diconjugate. The isolation of these polar metabolites for further characterization by NMR was aided by mass spectral analyses of HPLC fractions and solid phase extraction extracts during the isolation steps. The complete characterization of these novel diconjugates demonstrates that further phase II metabolism of polar conjugates such as sulfates could take place in vivo.

Alkynes↗
PubMed1995

The ovarian renin-angiotensin system. A paracrine-intracrine regulator of ovarian function.

We present a review that considers the regulation of ovarian function by the ovarian renin-angiotensin system. Evidence is presented that shows the ovarian renin-angiotensin system can regulate normal ovarian function by paracrine and intracrine mechanisms. In addition, the complexity that is inherent in the renin-angiotensin system conferred by multiple biological angiotensin peptides and multiple receptors is discussed. Evidence that a dysfunctional OVRAS induces ovarian pathology such as polycystic ovarian disease is also presented.

Animals↗
PubMed1994

Stabilization of an anthrapyrazole antitumour agent, DuP 937, on complexation with heptakis(2,6-di-O-methyl)-beta-cyclodextrin in aqueous solution.

DuP 937, an anthrapyrazole antitumour agent that is chemically unstable in aqueous solution, was shown, by absorption spectroscopy, to form an inclusion complex with heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM beta CD) in aqueous solution. Proton nuclear magnetic resonance spectroscopy was used to determine the stoichiometry and association constant of the complex. The 1:1 stoichiometry of the complex was established by the continuous variation method by following changes in the chemical shifts of aromatic protons of DuP 937. The complex association constants determined by different techniques used in this study were in the same order of magnitude. The kinetics of degradation of DuP 937 in aqueous solution were investigated as a function of DM beta CD concentration at pH 5.5 and 60 degrees C. The results indicated about a seven-fold increase in the stability of DuP 937 in the presence of DM beta CD in aqueous solution.

Anthraquinones↗
PubMed1994

A spectroscopic investigation of DuP 747 polymorphs.

DuP 747, a selective kappa agonist analgesic, was found to have at least two polymorphic forms, and this was confirmed by X-ray powder diffraction. DSC and thermomicroscopic studies indicated the polymorphic pair to be monotropic. Solubility studies suggested the relative stability of the two forms to be similar. The infrared (IR) and Raman spectra of the two crystal forms were significantly different, and their complementary nature was shown from the differences in peak intensities. Solid-state 13C-NMR data of the polymorphs showed only minor differences between the two forms. When viewed on the molecular level through the use of vibrational and NMR spectroscopies, the conformation of the molecule in the two polymorphs appears to be roughly equivalent. The magnitude of the spectral differences of the two polymorphs is, however, consistent with those that can be expected for two crystal forms that have resulted from different modes of packing, as caused by the solvent environment.

Analgesics↗
PubMed1993

Cyclic AMP decreases chemotaxis, invasiveness and lung colonization of H-ras transformed mouse fibroblasts.

We transfected mouse 10T1/2 fibroblasts with the H-ras oncogene and isolated lines expressing H-ras. One of the lines exhibited a highly malignant phenotype with the ability to produce large tumors and to colonize the lung after tail vein injection. In addition, the cells of this line showed increased collagenase IV production, directed migration and invasiveness, properties associated with the ability of tumor cells to metastasize. Since cyclic adenosine 3',5'-monophosphate (cAMP) is known to down-regulate ras expression, we exposed the malignant cells (Cl-1) to either N6, 2',0-dibutyryl cAMP (DB-cAMP) or 8-bromo cAMP (8-Br-cAMP), either with or without a phosphodiesterase inhibitor. We found that these treatments reduced the expression of ras, chemotaxis, invasiveness, and lung colonization of the ras-transformed cells. We therefore postulate that the malignancy of some cells may be regulated by alterations in the intracellular cAMP levels by suppressing ras expression and/or by reducing other activities required for the dissemination of tumor cells.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Ankle injuries in basketball players.

We carried out a retrospective study of the frequency of ankle sprains in basketball players. A questionnaire about previous ankle injuries, time off after such injuries, current ankle problems, personal data, number of practice hours and the use of prophylactic measures was sent out to 102 basketball players in a second division league in Sweden. Ninety-six players answered. 92% of them had suffered an ankle sprain while playing basketball, and of these 83% reported repeated sprains of one ankle. In the last two seasons, 78% of the players had injured at least one ankle. The injury frequency in the investigation was 5.5 ankle injuries per 1000 activity hours. 22% of the players used some kind of prophylactic support of their ankle joints. Because of the great number of ankle sprains and the disability in terms of time away from sports that they cause, prevention of these injuries is essential.

Adult↗
PubMed1993

The type 1 angiotensin-II receptor mediates intracellular calcium mobilization in rat luteal cells.

The intracellular cytosolic calcium concentration ([Ca]i) was determined in cultured rat luteal cells using the calcium-chelating dye fura-2 and microspectrofluorimetry. Angiotensin-II (Ang-II) induced a dose-dependent transient increase in [Ca]i (ED50, 9.0 +/- 6.5 nM). After the initial peak in [Ca]i, cytosolic calcium returned to a secondary elevated basal level that was dependent upon the presence of extracellular calcium. Pretreatment of rat luteal cells with Ang-II (100 nM) desensitized a subsequent response to a higher concentration (1 microM), but did not desensitize a prostaglandin F2 alpha (PGF2 alpha)-induced calcium flux. Although the peak increases in [Ca]i induced by Ang-II (1 microM) and PGF2 alpha (10 microM) were not significantly different, the plateau phase stimulated by PGF2 alpha was significantly higher (P < 0.05) than that stimulated by Ang-II (1 microM). Pretreatment of luteal cells with the type 2 Ang-II receptor antagonist PD 123319 (10 microM) did not inhibit calcium mobilization; however, Ang-II (1 microM)-induced calcium mobilization was dose dependently blocked by the type 1 Ang-II receptor antagonist Losartan (DuP 753). The ID50 for Losartan was 5.2 +/- 1.8 nM. Pretreatment of the luteal cells with the endoplasmic reticulum calcium ATPase inhibitor thapsigargin (1 microM) also blocked Ang-II-induced calcium mobilization. These data demonstrate the presence of the type 1 Ang-II receptor in rat luteal cells, through which Ang-II dose dependently mobilizes calcium from an intracellular source, probably the endoplasmic reticulum.

Adenosine Triphosphatases↗
PubMed1993

[Preoperative low-dose-rate versus high-dose-rate brachytherapy in stage IB cervix cancer. An efficacy study].

In women with stage IB (FIGO) carcinoma of the cervix, the authors investigated the efficacy of the manual low-dose rate (LDR) and afterloading high-dose rate (HDR) technique in terms of local freedom from tumor. It was found that in the 194 patients treated with the low-dose rate LDR-technique (computed dose point A 23.5 GY; point B 4.7 Gy), the surgical specimen was free of tumor in 37%. Among the 161 patients treated with the high-dose rate technique (point A11 Gy; point B 2 Gy), 41% of the surgical specimens were free of tumor. Follow-up examinations in the group receiving LDR-brachytherapy were carried out within a period of between ten and 90 months after treatment (average: 30.76 months). In 84% of the cases, NED was established. In the patient group treated with HDR-brachytherapy, follow-up examinations performed within a period of between six and 42 months after treatment (average 17.17 months), NED was found in 90%.

Adult↗