PubMed Health⌕ Search

Biomedical subjects

Z Szabo

Publications and source records attributed to Z Szabo.

At least 19 recordsLinked to original sources
PubMed2002

Transvaginal extraction of the laparoscopically removed spleen.

Laparoscopic removal of normal and moderately enlarged spleens has become the gold standard operation in recent years because its short operative time, technical safety, and quick patient recovery time. The best method for extraction of the removed spleen, however, has not yet been determined. The authors present a new method for the extraction of the laparoscopically removed spleen. Using a transvaginal approach, the organ is removed through an incision on the posterior vaginal wall and exteriorized in a laparobag. The procedure is similar to a routine vaginal hysterectomy, but is technically much simpler to perform.

Cholecystectomy, Laparoscopic↗
PubMed2001

Changes in sample collection and analytical techniques and effects on retrospective comparability of low-level concentrations of trace elements in ground water.

Ground-water sampling techniques were modified to reduce random low-level contamination during collection of filtered water samples for determination of trace-element concentrations. The modified sampling techniques were first used in New Jersey by the US Geological Survey in 1994 along with inductively coupled plasma-mass spectrometry (ICP-MS) analysis to determine the concentrations of 18 trace elements at the one microgram-per-liter (microg/L) level in the oxic water of the unconfined sand and gravel Kirkwood-Cohansey aquifer system. The revised technique tested included a combination of the following: collection of samples (1) with flow rates of about 2 L per minute, (2) through acid-washed single-use disposable tubing and (3) a single-use disposable 0.45-microm pore size capsule filter, (4) contained within portable glove boxes, (5) in a dedicated clean sampling van, (6) only after turbidity stabilized at values less than 2 nephelometric turbidity units (NTU), when possible. Quality-assurance data, obtained from equipment blanks and split samples, indicated that trace element concentrations, with the exception of iron, chromium, aluminum, and zinc, measured in the samples collected in 1994 were not subject to random contamination at 1 microg/L. Results from samples collected in 1994 were compared to those from samples collected in 1991 from the same 12 PVC-cased observation wells using the available sampling and analytical techniques at that time. Concentrations of copper, lead, manganese and zinc were statistically significantly lower in samples collected in 1994 than in 1991. Sampling techniques used in 1994 likely provided trace-element data that represented concentrations in the aquifer with less bias than data from 1991 when samples were collected without the same degree of attention to sample handling.

Environmental Monitoring↗
PubMed2001

Coordinate regulation of canine glomeruli and adrenal angiotensin receptors by dietary sodium manipulation.

BACKGROUND: This study evaluated the effects of dietary sodium manipulation in dogs on the regulation of canine angiotensin receptors (cAT1 and cAT2) in the kidney and adrenal. METHODS: Isolated glomeruli and membranes from renal medulla and the adrenal gland were used in radioligand binding assays from two groups of dogs: dogs maintained on low-sodium diet for two weeks followed by a high-sodium diet for two weeks (H), and dogs were maintained on the reverse schedule (L). RESULTS: Analysis of the binding data showed that dietary sodium manipulation had no significant effects on cAT1 and cAT2 receptor binding affinities in glomeruli, renal medulla, and adrenal tissues. In contrast, dietary sodium loading induced a marked increase in cAT1 receptor expression in both the glomeruli and adrenal compared with receptor expression in salt-restricted animals [H/L ratio: glomeruli (1.5), renal medulla (1.1), adrenal (1.6)] that inversely correlated with the activity of the plasma renin angiotensin system. Conversely, adrenal cAT2 receptor expression was regulated in an inverse manner in the H and L animal groups [H/L ratio: 0.7]. CONCLUSIONS: This study demonstrates that renal glomerular and adrenal AT1 receptors in the dog are coordinately down-regulated by dietary sodium restriction compared with sodium loading, which is distinctly different from the reciprocal regulation observed for rat AT1 receptors in these tissues. Collectively, these data suggest that postreceptor events in dogs are determinants of the aldosterone response observed during sodium restriction. These findings have important implications for the regulation of the renin-angiotensin system in humans, and suggest that coordinate regulation of AT1 receptors in the adrenal and glomeruli represent a negative feedback mechanism that when functioning normally prevents fluctuations of arterial blood pressure and development of arterial hypertension in response to changes in dietary sodium.

Adrenal Glands↗
PubMed2001

Magnetic resonance image analysis by information theoretic criteria and stochastic site models.

Quantitative analysis of magnetic resonance (MR) images is a powerful tool for image-guided diagnosis, monitoring, and intervention. The major tasks involve tissue quantification and image segmentation where both the pixel and context images are considered. To extract clinically useful information from images that might be lacking in prior knowledge, we introduce an unsupervised tissue characterization algorithm that is both statistically principled and patient specific. The method uses adaptive standard finite normal mixture and inhomogeneous Markov random field models, whose parameters are estimated using expectation-maximization and relaxation labeling algorithms under information theoretic criteria. We demonstrate the successful applications of the approach with synthetic data sets and then with real MR brain images.

Algorithms↗
PubMed2001

In vivo labeling of endothelin receptors with [(11)C]L-753,037: studies in mice and a dog.

UNLABELLED: Endothelin (ET) is a potent mammalian vasoconstrictive peptide and a pressor agent. Its 3 isoforms, ET-1, ET-2, and ET-3, mediate several physiologic actions in several organ systems, binding to 2 major receptor subtypes: ET(A) and ET(B). This study was undertaken to evaluate [(11)C]L-753,037 [(+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxy-propyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno [1,2-beta]pyridine-6-carboxylate), a new mixed ET receptor A and B antagonist, as a tracer for in vivo labeling of ET receptors in mice and a dog. METHODS: [(11)C]L-753,037 was synthesized, purified, and formulated from a normethyl precursor, L-843,974, and [(11)C]H(3)I. The tracer was studied for its in vivo kinetics, biodistribution, and ET receptor binding characteristics in mice. In the dog, PET imaging was performed to evaluate binding of [(11)C]L-753,037 to ET receptors in the heart. Specificity of binding was studied in the heart with the selective ET(A) antagonist L-753,164. RESULTS: Kinetic studies in mice showed highest tracer uptake at 5 min after injection in liver (25.0 percentage injected dose per gram [%ID/g]), kidneys (18.7 %ID/g), lungs (15.2 %ID/g), and heart (5.6 %ID/g). Initial high uptake in liver, lungs, and kidneys was followed by rapid washout during the next 10 min and a very slow clearance during the time of observation (2 h after injection). By contrast, the radioactivity in the heart remained constant over 2 h. Administration of both ET(A) (L-753,164) and mixed ET(A)/ET(B) (L-753,137) receptor antagonists resulted in dose-dependent inhibition of [(11)C]L-753,037 binding in mouse heart, lungs, and kidneys but not in the liver. Radioactivity in the brain was very low, indicating that the tracer does not cross the blood-brain barrier. In the dog, a dynamic PET study of the heart showed high tracer accumulation at 55-95 min after injection. Injection of L-753,164 at 30 min before [(11)C]L-753,037 administration led to a significant reduction in tracer binding. [(11)C]methyl triphenyl phosphonium was used as a tracer for reference images of the dog heart muscle. CONCLUSION: The results suggest that [(11)C]L-753,037 binds to ET receptors in vivo and is, therefore, a promising candidate for investigation of these receptors and their occupancy by ET receptor antagonists using PET.

Animals↗
PubMed2000

Toxicodynamics and long-term toxicity of the recreational drug, 3, 4-methylenedioxymethamphetamine (MDMA, 'Ecstasy').

The recreational drug, (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), is a potent serotonin (5-HT) neurotoxin in animals. Whether humans who use MDMA incur 5-HT neural injury is unknown. The present studies utilized positron emission tomography (PET) in conjunction with the 5-HT transporter ligand, [11C]McN-5652 to assess the status of brain 5-HT neurons in human MDMA users. Like nonhuman primates treated with neurotoxic doses of MDMA, humans with a history of MDMA use showed lasting decrements in global brain [11C]McN-5652 binding, with decreases in [11C]McN-5652 binding positively correlated to the extent of previous MDMA use. These results suggest that human MDMA use results in brain 5-HT neurotoxicity.

Animals↗
PubMed2000

Suturing and knotting techniques for thoracoscopic cardiac surgery.

The preceding description of E-CABG may seem excessively detailed, even redundant, for trained cardiac surgeons; however, the authors' extensive experience with training surgeons on endoscopic techniques suggests that, despite a high level of proficiency and dexterity that a surgeon may possess in open surgery, becoming equally proficient and dexterous in the endoscopic environment is not simple. Participating in an in-depth, systematic endoscopic microvascular surgery training program in a laboratory setting is essential before applying the previously described E-CABG techniques in humans. The E-CABG procedure is one of the most challenging endoscopic techniques. Successful completion of this procedure requires that the surgeon be motivated to succeed and willing to invest the time and effort necessary to develop the new skills. Also critical is the avoidance of the temptation to use devices and systems that promise to obviate the need to bother with learning these difficult endoscopic skills. Long term results of the minimally invasive approach remain to be defined. However, some early studies of port-access procedures are encouraging. To date, a prospective randomized clinical trial comparing conventional LAD bypass to E-CABG has not been conducted. Although most investigators believe that long term patency of the IMA to the LAD using either technique should be the same, this is as yet unproven. Nonetheless, the adaption of endoscopic skills by the cardiac surgeon will further advance the evolution of this specialty.

Coronary Artery Bypass↗
PubMed2000

Membrane-permeabilizing activities of cyclic lipodepsipeptides, syringopeptin 22A and syringomycin E from Pseudomonas syringae pv. syringae in human red blood cells and in bilayer lipid membranes.

The pore-forming activities of cyclic lipodepsipeptides (CLPs), syringopeptin 22A (SP22A) and syringomycin E (SRE) were compared on the human red blood cell (RBC) membrane and on bilayer lipid membranes (BLMs). SP22A above a concentration of 4 x 10(5) molecules/cell significantly increased the RBC membrane permeability for 86Rb. With electric current measurements on BLM, it was proved that like SRE, the SP22A formed two types of ion channels in the membrane, small and large, the latter having six times larger conductance and longer dwell time. Both CLPs formed clusters consisting of six small channels, and the channel-forming activity of SP22A is about one order of magnitude higher than that of SRE. A Hill coefficient of 2-3 estimated from the concentration dependence of these CLPs-induced lysis gave a proof of the pore oligomerization on RBCs. Transport kinetic data also confirmed that SP22A pores were oligomers of at least three monomers. While SRE pores were inactivated in time, no pore inactivation was observed with SP22A. The 86Rb efflux through SP22A-treated RBCs approached the tracer equilibrium distribution with a constant rate; a constant integral current was measured on the BLM for as long as 2.5 h as well. The partition coefficient (Kp = 2 x 10(4) l/mol) between the RBC membrane and the extracellular space was estimated for SRE to be at least six times higher than that for SP22A. This finding suggested that the higher ion permeability of the SP22A-treated cells compared to that of SRE was the result of the higher pore-forming activity of SP22A.

Cell Membrane Permeability↗
PubMed2000

Column-switching HPLC for the analysis of plasma in PET imaging studies.

A column-switch high performance liquid chromatography method for the analysis of 4 mL of plasma is described with six examples of chromatography of [(11)C]-labeled positron-emission tomography imaging agents. Complete extraction of all but the most polar metabolites by the reverse phase capture column is achieved by disruption of plasma protein binding by 8 M urea.

Chromatography, High Pressure Liquid↗
PubMed2000

Novel treatment of conformational flexibility using interval analysis

A revolutionary new flexible conformational search technique is presented together with its application to geometrical docking. The algorithm is guaranteed to find all (even an infinite number of) solutions in a continuous manner. Examples are given using 2-(4'-amidinophenyl)pyruvate (APPA) docked to trypsin. Other potential applications are briefly discussed.

Journal Article↗
PubMed1999

Altered bladder function in transgenic mice expressing rat elastin.

The elasticity of tissues subjected to repeated deformation is provided by the presence of elastic fibers in the extracellular matrix (ECM). The most abundant component of elastic fibers is elastin, whose soluble precursor is tropoelastin. To establish the role elastin plays in the bladder, this study describes the biosynthetic, histologic, and physiologic consequences of expression of an isoform of rat tropoelastin in transgenic mouse bladder. The polymerase chain reaction (PCR) was used to determine expression of a rat tropoelastin minigene in transgenic mice. Histochemical methods were used to demonstrate changes in elastic fibers in frozen sections of bladder. Cystometric analysis was carried out in transgenic and non-transgenic mice, prior to and after 3 weeks of partial outlet obstruction. The PCR assay demonstrated that bladder tissue of transgenic mice expressed rat tropoelastin mRNA, whereas non-transgenes did not. Increased deposition of elastic fibers was demonstrated with the Verhoeff-van Gieson stain. Bladders of transgenic animals were more compliant than bladders of their non-transgenic littermates. Partial outlet obstruction resulted in increased bladder volume and more compliant bladders in non-transgenic mice. In contrast, the bladder volume and compliance in transgenes was almost unchanged by obstruction. This study demonstrates that normal elastic fiber assembly is prerequisite for the compliant properties of the bladder wall. Moreover, the response of the bladder to obstruction is critically influenced by elastin synthesis.

Animals↗
PubMed1999

Effect of tracer metabolism on PET measurement of [11C]pyrilamine binding to histamine H1 receptors.

The present study was carried out to investigate the time course of [11C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [11C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [11C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [11C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [11C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [11C]pyrilamine. Based on the rat data, the contribution of 11C-labeled metabolites to total [11C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [11C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [11C]pyrilamine by brain tissue itself. Therefore, [11C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [11C]pyrilamine binding to histamine H1 receptors.

Adult↗
PubMed1999

The value of a baseline bone scan in patients with newly diagnosed prostate cancer.

PURPOSE: This study evaluated the role of bone scans in managing newly diagnosed, untreated prostate cancer. METHODS: Two hundred seventy consecutive staging bone scans in patients (mean age, 69 years) with newly diagnosed prostate cancer who had serum prostate-specific antigen (PSA) determinations and biopsies between January 1995 and October 1997 were evaluated retrospectively. RESULTS: The bone scans were positive for metastatic bone disease in 24 patients and negative in 246. Serum PSA levels, the number of positive biopsy cores, the extent of tumor in the prostate gland, and Gleason scores were all significantly correlated with scintigraphic bone metastases (P < 0.0001 for each). Of the 177 patients with PSA levels less than 10 ng/ml, three had bone metastases. Bone metastases were found in 2 of 34 patients with PSA levels of 10.1 to 20 ng/ml, in 3 of 29 patients with PSA values of 20.1 to 50 ng/ml, and in 16 of 30 patients with PSA levels greater than 50.1 ng/ml. Only one patient had a bone metastasis when the prostate cancer involved fewer than 2 biopsy cores (1 of 135) or when disease was confined to one lobe (1 of 131), but the incidence increased significantly when the malignancy involved three or more biopsy cores (20 of 114) or disease was present in both prostate lobes (20 of 118). Four of 160 patients with Gleason scores less than 6 had bone metastases, whereas 20 of 110 patients with Gleason scores greater than 7 had bone metastases. CONCLUSIONS: The likelihood of bone metastases is low in patients with newly diagnosed, untreated prostate cancer when the initial PSA level was less than 10 ng/ml, the number of positive biopsy cores was less than 2, tumor was confined to one lobe, or the Gleason score was less than 6. However, none of these criteria can be used to exclude metastatic bone disease. A baseline bone scan is an important staging procedure and should be obtained to provide maximum data for clinical management of the disease.

Aged↗
PubMed1999

Kinetic analysis of [11C]McN5652: a serotonin transporter radioligand.

The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](-)McN5652. The impulse response function was calculated by deconvolution analysis of regional time-activity curves, and its peak value (f(max)), its retention value at 75 minutes (fT), and its normalized retention (f(rel) = fT/f(max)) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume (DV(T)) and its specific binding component (DV(S)). Both the noncompartmental (fT,f(rel)) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](-)McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters k1 and k2 and that also included the parameter of regional cerebral blood volume (BV). The parameter f(rel) demonstrated low between-subject variance (coefficient of variation [CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, f(rel) demonstrated further improvement in correlation (r = 0.814) and midbrain to cerebellum ratio (3.09). The variance of the distribution volumes was acceptable when the logarithmic transform lnDV was used instead of DV (17% for the three-parameter model), but correlation of this compartmental parameter was slightly less (r = 0.652 for the three-parameter model) than the correlation of the noncompartmental f(rel) with the known density of SERT, and the midbrain to cerebellum ratio was only 1.5 (uncorrected) and 1.8 (corrected). At the expense of increasing variance, the correlation was increased after correction for nonspecific binding using the inactive enantiomer (r = 0.694; CV = 22%). These results indicate that the kinetics of [11C](+)McN5652 can best be described by a one-tissue compartment model with three parameters (k1, k2, and BV), and that both the noncompartmental parameter f(rel) and the compartmental distribution volumes have the potential for quantitative estimation of the density of SERT. Further validation of the radioligand in experimental and clinical situations is warranted.

Adult↗
PubMed1999

Enhanced uptake of [11C]TPMP in canine brain tumor: a PET study.

UNLABELLED: In vitro studies have demonstrated the membrane potential-dependent enhanced uptake of phosphonium salts, including [3H]triphenylmethylphosphonium (TPMP), into mitochondria of carcinoma and glioma-derived tumor cells, suggesting the potential use of phosphonium salts as tracers for tumor imaging. This study characterizes the in vivo uptake of [11C]TPMP in canine brain glioma using PET. METHODS: Dynamic paired PET studies of [11C]TPMP followed by [68Ga]ethylenediaminetetraacetic acid (EDTA) were performed 4 d before and 9 d after tumor cell inoculation. Graphical analysis was used to evaluate [11C]TPMP retention in tumor tissue. Distribution of tracer uptake was compared with tumor histological sections. RESULTS: [11C]TPMP exhibited enhanced uptake and prolonged retention in tumor cells. Patlak plot was linear over the 20- to 95-min postinjection period (r = 0.97 +/- 0.1). [68Ga]EDTA exhibited a gradual washout from the tumor tissue. The tumor-to-normal brain uptake ratio at 55 to 95 min postinjection was 47.5 for [11C]TPMP and 8.1 for [68Ga]EDTA. Qualitative comparison with histological sections indicated that [11C]TPMP enhanced uptake was restricted to the tumor area. CONCLUSION: The enhanced uptake and prolonged retention in tumor suggest [11C]TPMP as a promising means for imaging of gliomas in dogs. The need for studies in humans is indicated.

Animals↗
PubMed1998

Positron emission tomographic evidence of toxic effect of MDMA ("Ecstasy") on brain serotonin neurons in human beings.

BACKGROUND: (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular recreational drug that selectively damages brain serotonin (5-HT) neurons in animals at doses that closely approach those used by humans. We investigated the status of brain 5-HT neurons in MDMA users. METHODS: We enrolled 14 previous users of MDMA who were currently abstaining from use and 15 controls who had never used MDMA. We used positron emission tomography (PET) with the radioligand carbon-11-labelled McN-5652, which selectively labels the 5-HT transporter. We analysed whether there were differences in 5-HT transporter binding between abstinent MDMA users and participants in the control group. Blood and urine samples were taken and tested to check for abstinence. FINDINGS: MDMA users showed decreased global and regional brain 5-HT transporter binding compared with controls. Decreases in 5-HT transporter binding positively correlated with the extent of previous MDMA use. INTERPRETATION: Quantitative PET studies with a ligand selective for 5-HT transporters can be used to assess the status of 5-HT neurons in the living human brain. We show direct evidence of a decrease in a structural component of brain 5-HT neurons in human MDMA users.

Adult↗
PubMed1998

In vivo detection of short- and long-term MDMA neurotoxicity--a positron emission tomography study in the living baboon brain.

The present study evaluated short- and long-term effects of MDMA (3,4-methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN 5652, a potent 5-HT transporter ligand, as well as [11C]RTI-55, a cocaine derivative which labels both 5-HT and dopamine transporters. Following baseline PET scans with [11C](+)McN5652, [11C](-)McN5652 (the inactive enantiomer of the active enantiomer [11C](+)McN5652) and [11C]RTI-55, a baboon was treated with MDMA (5 mg/kg, s.c., twice daily for four consecutive days). PET studies at 13, 19, and 40 days post-MDMA revealed decreases in mean radioactivity levels in all brain regions when using [11C](+)McN 5652, but not with [11C](-)McN5652 or [11C]RTI-55. Reductions in specific [11C](+)McN5652 binding (calculated as the difference in radioactivity concentrations between (+) and (-)[11C]McN5652) ranged from 44% in the pons to 89% in the occipital cortex. PET studies at 9 and 13 months showed regional differences in the apparent recovery of 5-HT transporters, with increases in some brain regions (e.g., hypothalamus) and persistent decreases in others (e.g., neocortex). Data obtained from PET studies correlated well with regional 5-HT axonal marker concentrations in the CNS measured after sacrifice of the animal. The results of these studies indicate that PET imaging of the living nonhuman primate brain with [11C](+)McN5652 can detect changes in regional 5-HT transporter density secondary to MDMA-induced neurotoxicity. Using PET, it should also be feasible to use [11C](+)McN5652 to determine whether human MDMA users are also susceptible to MDMA's neurotoxic effects.

Animals↗