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Biomedical subjects

A Nemes

Publications and source records attributed to A Nemes.

At least 19 recordsLinked to original sources

[Impending paradoxical embolism].

The case history of a 49-year-old female patient is reported, who was operated on because of varicose vein in the left lower extremity. A few days after the operation serious signs of cerebrovascular insult appeared. The clinical picture and the result of an urgent transoesophageal echocardiography are described; a serpentine thrombus was found to be trapped in the patent foramen ovale. During continuous intravenous heparin treatment, the patient gradually recovered, but a residual neurological deficit could be detected on discharge from the hospital. Six days after the admission, repeated transoesophageal echocardiographic examination showed no signs of intracardiac thrombus. The clinical feature of the illness, the predisposing factors, the diagnostic and therapeutic possibilities are discussed.

Diagnosis, Differential↗

Capillary electrophoresis separation of vinpocetine and related compounds: prediction of electrophoretic mobilities in partly aqueous media.

Offord's equation, a relationship between electrophoretic mobility and charge, size and shape of peptides, has been extended to quantitate the electrophoretic mobility of vinca alkaloids. Partly aqueous protonation constants and the derived theoretical mobilities have been proven to be able to predict experimental electrophoretic mobilities. In practice, seven vincamine derivatives of very low water-solubility were separated by capillary electrophoresis. Buffer total concentration, apparent pH and methanol content, the three most important parameters of the running buffer, were used in triangular resolution mapping to characterize separation. Even though electrophoresis is well known to slow down in partly aqueous media, under our optimized circumstances a baseline separation was achieved within 8 min in each case.

Electrophoresis, Capillary↗

Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems.

Pten/Mmac1+/- heterozygous mice exhibited neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus. Loss of the wild-type allele was detected in neoplasms of the thymus and liver. Surprisingly, tumors of the gastrointestinal epithelium developed in association with gut lymphoid tissue. Tumors of the endometrium, thyroid, prostate, and liver were not associated with lymphoid tissue and appeared to be highly mitotic. In addition, these mice have nonneoplastic hyperplasia of lymph nodes that was caused by an inherited defect in apoptosis detected in B cells and macrophages. Examination of peripheral lymphoid tissue including lymphoid aggregates associated with polyps revealed that the normal organization of B and T cells was disrupted in heterozygous animals. Taken together, these data suggest that PTEN is a regulator of apoptosis and proliferation that behaves as a "landscaper" tumor suppressor in the gut and a "gatekeeper" tumor suppressor in other organs.

Animals↗

Proton speciation and microspeciation of vinpocetine and related compounds in aqueous and biomimetic media.

PURPOSE: The determination of protonation macroconstants of twelve compounds in the vincamine drug family and the determination of protonation microconstants of cis- and trans-apovincaminic acid in media of various solvent composition to characterise their site-specific basicity and to estimate the concentration of the membrane-penetrating and receptor-binding forms. METHODS: UV-pH titrations have been used to determine the protonation macroconstants in 10-43 wt% methanol/water mixtures. Yasuda-Shedlovsky extrapolation was applied to obtain aqueous logK values for compounds sparingly soluble in water. Protonation microconstants were also determined by deductive methods for compounds of free carboxylic group. RESULTS: In the case of the two water-soluble compounds the extrapolated and the directly measured aqueous logK values were in good agreement, verifying all other extrapolated data. Compounds of cis-D/E ring anellation are 0.4-0.8 logK units more basic than their epimeric, trans counterparts. The pH-dependent distribution of apovin-caminic acid microspecies in aqueous and membrane-like media is depicted in microspeciation diagrams. CONCLUSIONS: The N(4) nitrogen is more shielded by the adjacent ethyl group in trans-D/E ring anellation eburnanes than in cis ones, as reflected by the protonation constants. Solvent-dependent basicity data predict superiority of trans isomers in lipophilicity and membrane-penetrating ability.

Hydrogen-Ion Concentration↗

Odorant receptors govern the formation of a precise topographic map.

Olfactory neurons expressing a given odorant receptor project with precision to 2 of the 1800 glomeruli within the olfactory bulb to create a topographic map of odor quality. We demonstrate that deletions or nonsense mutations in the P2 odorant receptor gene cause the axons of these cells to wander rather than converge on a specific glomerulus. Receptor substitution experiments that replace the P2 gene with the coding region of the P3 gene result in the projection of P3-->P2 axons to a glomerulus touching the wild-type P3 glomerulus. These data, along with additional receptor substitutions, indicate that the odorant receptor plays an instructive role in the establishment of the topographic map.

Animals↗

Mice deficient in G(olf) are anosmic.

We have used gene targeting to examine the role of the G alpha subunit, G(olf), in olfactory signal transduction. Mice homozygous for a null mutation in G(olf) show a striking reduction in the electrophysiological response of primary olfactory sensory neurons to a wide variety of odors. Despite this profound diminution in response to odors, the topographic map of primary sensory projections to the olfactory bulb remains unaltered in G(olf) mutants. Greater than 75% of the G(olf) mutant mice are unable to nurse and die within 2 days after birth. Rare surviving homozygotes mate and are fertile, but mutant females exhibit inadequate maternal behaviors. Surviving homozygous mutant mice also exhibit hyperactive behaviors. These behavioral phenotypes, taken together with the patterns of G(olf) expression, suggest that G(olf) is required for olfactory signal transduction and may also function as an essential signaling molecule more centrally in the brain.

Animals↗

Enhanced neuronal death from focal ischemia in AMPA-receptor transgenic mice.

Excitatory amino acid (EAA) receptors play an important role in neuronal cell death in acute cerebral ischemia. Blocking the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype of EAA receptor has been shown to reduce cell death in global cerebral ischemia. However their role in focal stroke, although suggestive, has remained more contentious. To clarify this issue, we generated transgenic mice overexpressing the AMPA receptor (AMPAR) subunit GluR2-flip which would increase AMPAR-mediated currents. Excitatory neurons in these transgenic mice are thus predicted to be more susceptible than wild-type neurons to EAA (glutamate)-induced excitotoxic damage. Consistent with this prediction, cultured neurons from transgenic mice had a lower LD50 for exposure to glutamate (10(-3)-10(-5) M for 5 min) compared to wild-type neurons. Moreover, transgenic mice subjected to permanent focal ischemia of the middle cerebral artery (MCA) using the intralumenal filament model sustained larger infarctions compared to wild-type controls. Hence we have developed a genetic mouse model that demonstrates the crucial role of AMPAR containing GluR2-flip in the pathogenesis of focal hypoxic-ischemic neuronal cell death. This model will be a valuable tool in elucidating molecular mechanisms of glutamate excitotoxicity and evaluating the efficacy of glutamate receptor antagonists in attenuating post-ischemic neuronal cell death.

Alternative Splicing↗

Proximal bleeding control obtained by a balloon catheter in the surgical repair of a left supraclavicular traumatic arteriovenous fistula.

Endovascular procedures offer various methods for the treatment of posttraumatic arteriovenous fistulas. We report the treatment of a posttraumatic arteriovenous fistula between the left subclavian artery and internal jugular vein combined with a large subclavian false aneurysm. To avoid left thoracotomy we attained control of arterial bleeding by means of a transfemorally introduced balloon catheter advanced into the left subclavian artery. We found that the combination of endovascular procedures with classical surgery can reduce the risks in the treatment of arteriovenous fistulas.

Aged↗

Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty.

After limited experience with eversion endarterectomy of the internal carotid artery, comparison has been made between perioperative results obtained with the eversion technique and with the conventional method. The perioperative results of 715 consecutive cases of patch plasty of the internal carotid artery performed between January 1986 and December 1990 were reviewed and compared with perioperative data of 739 consecutive cases of eversion endarterectomy, performed between January 1991 and December 1993. The duration of surgery was also recorded. Statistical analysis was carried out, using chi2 test, Fisher's Z test and Student's t-test. The postoperative stroke rate was 2.9% in the conventional endarterectomy group, and 0.95% in cases of eversion endarterectomy (P<0.01); the stroke mortality rates were 1.8% and 0.54% respectively (P<0.05). Overall mortality rate was 2.9% in the conventional group and 0.95% in the eversion group (P<0.01): combined morbidity and mortality rate was 4% versus 1.35% (P<0.001). A statistically significant difference was found in favour of the eversion method between the duration of surgery (90.9 min versus 52.8 min; P<0.005) and between the mean clamp time (34.9 min versus 22.4 min: P<0.005). On the basis of these results, it is concluded that eversion endarterectomy of the internal carotid artery is a safe and rapid technique and its immediate results were superior to those obtained after conventional endarterectomy and patch plasty.

Adult↗

Visualizing an olfactory sensory map.

We have developed a genetic approach to visualize axons from olfactory sensory neurons expressing a given odorant receptor, as they project to the olfactory bulb. Neurons expressing a specific receptor project to only two topographically fixed loci among the 1800 glomeruli in the mouse olfactory bulb. Our data provide direct support for a model in which a topographic map of receptor activation encodes odor quality in the olfactory bulb. Receptor swap experiments suggest that the olfactory receptor plays an instructive role in the guidance process but cannot be the sole determinant in the establishment of this map. This genetic approach may be more broadly applied to visualize the development and plasticity of projections in the mammalian nervous system.

Animals↗

An overview of vascular surgery in Hungary.

The practice of vascular surgery in Hungary was initiated in 1952 and its progress can be seen as beginning with a "trial" stage from 1952 to 1960. During the period from 1960 to 1980, the first of the operations known today were performed, and since 1991, vascular surgery has become routinely practiced, with the number of vascular reconstructions each year exceeding 6,000. From a population of 10 million inhabitants in Hungary, a total of 6,892 arterial reconstructions were carried out during 1990 by 150 vascular surgeons, with a total of 400 allocated beds.

Humans↗

Estimation of impurity profiles of drugs and related materials Part 15. Identification of minor impurities in cimetidine.

Besides several known impurities in cimetidine, two additional compounds at levels below 0.1% were detected by ion-pair reversed-phase high-performance liquid chromatography (HPLC). The impurities were isolated from crude cimetidine using normal-phase preparative HPLC. 1H and 13C NMR and mass spectrometric investigations revealed the structures of the impurities to be 2,5-bis[(N'-cyano-N"-methyl)guanidinoethylthiomethyl]-4-methylimid azole (VII) and 1,8-bis[(N'-cyano-N"-methyl)guanidino]-3,6-dithiaoctane (VIII). These structures were verified by synthesis of the impurities and comparison of the spectra and chromatographic (HPLC and TLC) retention data of the isolated and synthesized materials.

Anti-Ulcer Agents↗

Eversion endarterectomy in surgery of the internal carotid artery.

A total of 361 eversion endarterectomies of the internal carotid artery have been carried out on 348 patients between January 1991 and December 1992. Of these patients, 126 were women and 222 were men; average age was 62.9 (range 42-84) years. Some 239 patients had hemispheric symptoms; 37 symptomless patients had a carotid endarterectomy before major vascular reconstruction, and 21 had the operation combined with heart surgery (19 aortocoronary bypasses, two valve replacements). In nine cases (2.5%) a 6-mm interposition graft was used because of unsuccessful eversion endarterectomy. Postoperative bleeding occurred in six patients (1.7%) and postoperative stroke in seven (1.9%); of these patients, four died and two still have mild neurological symptoms. Four reocclusions occurred during the first 6 months that the new method was used. Eversion endarterectomy of the internal carotid artery is a safe and useful technique and is comparable with standard endarterectomies. This technique may reduce the risk of restenosis.

Carotid Artery, Internal↗

Sp1 elements protect a CpG island from de novo methylation.

Animal somatic cell DNA is characterized by a bimodal pattern of methylation: tissue-specific genes are methylated in most cell types whereas housekeeping genes have 5' CpG islands which are constitutively unmethylated. Because methyl moieties derived from the gametes are erased in the morula and early blastula, this profile must be re-established in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation. Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Sp1 elements play a key role in protecting a CpG island in the adenine phosphoribosyltransferase (APRT) gene from de novo methylation. This recognition mechanism represents a critical step in embryogenesis, as it is responsible for setting up the correct genome methylation pattern which, in turn, is involved in regulating basal gene expression in the organism.

Adenine Phosphoribosyltransferase↗

Experimental deep venous replacement.

In altogether 48 adult mongrel dogs of both sexes with body weights between 15 and 25 kg, 3-5 cm long portions of the subrenal inferior vena cava were replaced by different vascular prostheses under intratracheal anaesthesia. During surgery, heparin sodium in an amount of 0.1 ml/kg body weight was administered intravenously to the animals, which was bound at the end of the surgery. In the postoperative period neither anticoagulant therapy measures for the inhibition of platelet aggregation were applied. In half of the experiments a 6-8 mm long arteriovenous fistula was prepared between the femoral artery and the femoral vein which was maintained permanently. The vascular prostheses were either of biological or of synthetic type; in one group within each type, prostheses without external support were implanted, while in the other group the prostheses had an external support.

Animals↗

[Laparoscopic cholecystectomy. Initial experiences].

Between February 1991 and July 1991, 74 laparoscopic cholecystectomies were performed. The number of all cholecystectomies during this period was 168. Two surgeons performed the operations. Stone in the common bile duct, old age, acute cholecystitis, severe obesity and heart rhythm disorders were regarded as contraindications. The duration of the operation was 45-210 min. (mean 127 min). The intervention was diverted to open cholecystectomy in 2 instances (2.7%). Early postoperative complications were observed in 2 cases (2.7%): biliary discharge and bleeding. Reoperation was necessary in one patient (1.3%) because of bleeding. There was no operative mortality. The mean duration of hospitalization was 5.6 days, and the mean postoperative period was 2.7 days. It is considered that, laporoscopic cholecystectomy can be carried out only by specialists in both bile surgery and laparoscopic techniques, provided that all the personal and technical conditions necessary for traditional cholecystectomies are at hand. Both medically and economically, the laparoscopic cholecystectomy results attain or even exceed those of the traditional open technique.

Adult↗