Bibliometric analysis of lung transplantation research articles.

BACKGROUND: In the last 30 years lung transplantation has proven to be a lifesaving therapeutic option for patients with end-stage lung disease. The objective of this study was to perform a bibliometric analysis of lung transplantation research articles. METHOD: A bibliometric evaluation of the evolution of scientific production in the field of lung transplantations between 1989 and 2009 was conducted using the ISI Web of Science. The search terms selected were "lung transplant" OR "pulmonary transplant". Specific features including year of publication, language, geographical distribution, first author, main journal publishing these articles, journals publishing highly cited articles, and institutional affiliation were analyzed. The citation characteristics of articles were additionally analyzed. RESULTS: A total of 6409 (58.0 %) research articles were found. The time trend of the number of articles showed an increase of more than 6.81 between 1989 and 2009. North America contributed 50.4 % and Europe contributed 46.0 % of published articles. The greatest number of contributions came from the USA (43.6 %), followed by England (9.1 %) and Germany (8.6 %). There were 104 522 citations of these articles by 25 July 2010. The average citation per article was 16.31. The New England Journal of Medicine ranked first with regard to the number of articles and the number of highly cited articles. G. A. Patterson, Washington University, and the US National Institutes of Health (NIH) were the top author, institution and funding agency, respectively. CONCLUSION: The number of publications and the scientific interest in lung transplantation has increased rapidly in recent years. Citations of articles published in the field of lung transplantation are increasing and the numbers of uncited articles are fewer compared to the average citations of articles and uncited articles in the field of medicine.

Effect of magnetic resonance imaging on microleakage of amalgam restorations: an in vitro study.

OBJECTIVES: The technique of MRI, using powerful magnets, plays an important role in the diagnosis of diseases of the head and neck without any ionizing radiation. Because of the potential hazard imposed by the presence of ferromagnetic metals, patients with implanted metallic objects are excluded from MRI. However, amalgam restorations seem to be safe. The purpose of this study was to evaluate microleakage of amalgam restorations following MRI. METHODS: 63 human freshly extracted premolars were divided into 3 groups based on 3 high-copper amalgams used to restore standard class V preparations on both buccal and lingual surfaces. Three different amalgam materials were used: Cinalux, GS-80 and Vivacap. The teeth were transferred into saline solution for 2 months at room temperature and then sectioned mesiodistally. MRI was randomly applied to one half of each section, and the other half was kept as a control. Following MRI, all specimens were immersed in a dye solution, sectioned and scored for any microleakage using a stereomicroscope. RESULTS: Differences in microleakage within each group following MRI were significant in the GS-80 and Vivacap groups but not in the Cinalux group. However, there was no significant difference between the three groups regarding the microleakage score. CONCLUSIONS: The results of this study suggest that MRI is not a completely safe technique in patients with amalgam restorations. It was shown that the main effect of fields led to the appearance of thermoelectromagnetic convection, which is responsible for the enhancement of the diffusion process, grain boundary migration and vacancy formation resulting in microleakage.

In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans.

Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible.

Synthesis and evaluation of fluorine-18 labeled glyburide analogs as beta-cell imaging agents.

Glyburide is a prescribed hypoglycemic drug for the treatment of type 2 diabetic patients. We have synthesized two of its analogs, namely N-[4-[beta-(2-(2'-fluoroethoxy)-5-chlorobenzenecarboxamido)ethyl]benzenesulfonyl]-N'-cyclohexylurea (2-fluoroethoxyglyburide, 8b) and N-[4-[beta-(2-(2'-fluoroethoxy)-5-iodobenzenecarboxamido)ethyl]benzenesulfonyl]-N'-cyclohexylurea (2-fluoroethoxy-5-deschloro-5-iodoglyburide, 8a), and their fluorine-18 labeled analogs as beta-cell imaging agents. Both F-18 labeled compound 8a and compound 8b were synthesized by alkylation of the corresponding multistep synthesized hydroxy precursor 4a and 4b with 2-[(18)F]fluoroethyl tosylate in DMSO at 120 degrees C for 20 minutes followed by HPLC purification in an overall radiochemical yield of 5-10% with a synthesis time of 100 minutes from EOB. The octanol/water partition coefficients of compounds 8a and 8b were 141.21 +/- 27.77 (n = 8) and 124.33 +/- 21.61 (n = 8), respectively. Insulin secretion experiments of compounds 8a and 8b on rat islets showed that both compounds have a similar stimulating effect on insulin secretion as that of glyburide. In vitro binding studies showed that approximately 2% of compounds 8a and 8b bound to beta TC3 and Min6 cells and that the binding was saturable. Preliminary biodistribution studies in mice showed that the uptake of both compounds 8a and 8b in liver and small intestine were high, whereas the uptake in other organs studied including pancreas were low. Additionally, the uptake of compound 8b in vivo was nonsaturable. These results tend to suggest that compounds 8a and 8b may not be the ideal beta-cell imaging agents.

Microleakage of direct and indirect composite restorations with three dentin bonding agents.

This study evaluated the marginal sealing ability of direct and indirect (inlay) resin composite restorations with three dentin bonding systems. Forty-eight freshly extracted bovine incisor teeth were randomly assigned to four groups for bonding with Syntac Single-Component, Excite (Vivadent, Liechtenstein), ScotchBond Multi-Purpose Plus (3M Dental Products, St Paul, MN 55144, USA) and a control with no bonding agents. Class V cavities were cut in both buccal and lingual surfaces. The coronal half of each preparation was in enamel and the gingival half was in cementum or dentin. Half of the specimens in each group were restored with direct and the remainder with indirect technique. The teeth were stored in 37 degrees C water for 30 days, then thermocycled. After immersion in 0.5% basic fuchsin, the teeth were cut faciolingually and evaluated for dye penetration using a binocular stereomicroscope. There was no significant difference among the bonding systems for either the direct or indirect technique or between the two techniques used for each system, however, the indirect technique showed significantly (p = 0.001) less microleakage than the direct technique in control groups. All groups showed more leakage at the cementum margins except Excite with direct technique, where microleakage at the incisal and gingival margins was almost equal.

A simplified one-pot synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy.

9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG, 2) has been synthesized by nucleophilic substitution of N(2)-(p-anisyldiphenylmethyl)-9-[[1-(p-anisyldiphenylmethoxy)-3-toluenesulfonyloxy-2-propoxy]methyl]guanine (1) with potassium [18F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 degrees C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 degrees C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 degrees C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 degrees C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126 +/- 0.022, n=5 and 0.165 +/- 0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ( approximately 5-30 microg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains approximately 10-25 microg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is readily amenable for automation.

N-(n-Benzylpiperidin-4-yl)-2-[18F]fluorobenzamide: a potential ligand for PET imaging of breast cancer.

N-(N-Benzylpiperidin-4-yl)-2-[(18)F]fluorobenzamide (2), a potential ligand for PET imaging of sigma receptor, has been found to be a potential agent for detection of breast cancer. In vivo studies in severe combined immunodeficient (SCID) mice bearing MDA-MB231 tumors showed that the uptake of compound 2 in these tumors was high (3.8%/g); the ratios of tumor/muscle and tumor/blood were 6.2 and 7.0, respectively, at 1 h postinjection. Pretreatment of SCID mice with haldol increased the uptake of compound 2 in blood, muscle, and other well-perfused organs while decreasing its uptake in tumors. The ratios of tumor/muscle and tumor/blood decreased from 6.2 and 7.0 to 1.3 and 1.1, respectively, at 1 h postinjection. At 2 h postinjection, the ratios of tumor/muscle and tumor/blood decreased from 4.9 and 7.8 to 1.4 and 1.4, respectively. The tumor uptake of compound 2 in SCID mice bearing primary tumor explants from a human breast cancer patient was lower than that in MDA-MB231 tumors (1.66%/g versus 3.78%/g), and the ratios of tumor/muscle and tumor/blood were 3.5 and 3.7, respectively, at 1 h postinjection. These results suggest that compound 2 may be a potential ligand for PET imaging of breast cancer.

N-(N-benzylpiperidin-4-yl)-2-[18F]fluorobenzamide: a potential ligand for PET imaging of sigma receptors.

Four nitro- and fluorobenzamides (1-4) have been synthesized in good yields from nitro- and fluoro-substituted benzoyl chloride with 4-amino-1-benzylpiperidine. In vitro studies showed that these compounds have high affinities to sigma receptors. N-(N-Benzylpiperidin-4-yl)-2-fluorobenzamide (3), in particular, bound to sigma receptors with high affinity (Ki = 3.4 nM, guinea pig brain membranes) and high selectivity (sigma-2/sigma-1 = 120). It was, therefore, labeled with 18F and evaluated as a sigma receptor radioligand. N-(N-Benzylpiperidin-4-yl)-2-[18F]fluorobenzamide (3a) was synthesized in one step by nucleophile substitution of the 2-nitro precursor (1) with [18F]fluoride in DMSO at 140 degrees C for 20 min followed by purification with HPLC in 4-10% yield (decay corrected). The synthesis time was 90 min and the specific activity was 0.4-1.0 Ci/mumol. Tissue distribution in mice revealed that the uptakes of 3a in the brain, heart, liver, lungs, spleen, kidneys and small intestine were high, and the radioactivity in these organs remained constant from 60 to 120 min post-injection. The radioactivity in the bone did not significantly increase, suggesting in vivo defluorination may not be the major route of metabolism of 3a in mice. Blocking studies with haloperidol in rats indicated that the uptake of compound 3a in the rat brain was selective to haloperidol-sensitive sigma sites. These results suggest that compound 3a is a potent sigma receptor radioligand and may be a potential ligand for PET imaging of sigma receptors in humans.

[The ECG changes during the performance of hemodialysis using dialysis solution concentrates with different potassium levels in patients with chronic kidney failure and normokalemia]. / Izmeneniia na EKG pri provedenii gemodializa s ispol'zovaniem kontsentrata dializiruiushchego rastvora s razlichnym soderzhaniem kaliia u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu i normokaliemiei.i

Seven patients with chronic renal failure and normokalemia underwent 56 hemodialysis procedures (4 procedures each) using a dialysis solution concentrate containing 2.0 mmol/l (4 procedures) and 3.0 mmol/l potassium (4 procedures). Other electrolytes in the concentrates were the same. It was found that administration of 2.0 mmol/l K concentrate in 4 patients led to ECG changes indicative of hypokalemia. The changes can be managed by slowing down the speed of K elimination from the blood. This is achieved with the solution concentrate containing K 3.0 mmol/l.