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Biomedical subjects

A Mayer

Publications and source records attributed to A Mayer.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Results of surgical treatment of esophageal cancer].

At the Department of Surgery of the Szent Imre Hospital 53 esophageal operations were performed between August 1, 1995 and August 1, 2000 because of malignant disease. We retrospectively analyze the operations of 37 male and 16 female patients, and compare the results with published data. We describe the preparation and medical examination of the patients and the problems of intraoperative or potential complications and their prevention. We emphasise the importance of postoperative treatment and monitoring, as well as difficulties of the surgery and physiotherapy after operation. We think, that with adequate perioperative background and surgical treatment these operations can be performed safely in our department. These are basic procedures in the treatment of a malignant disease of the digestive system with serious economico-medical problems.

Aged↗
PubMed2001

The influence of different glucose concentrations in haemodialysis solutions on metabolism and blood pressure stability in diabetic patients.

In recent years the percentage of diabetic patients on haemodialysis has increased. Considering the high frequency of intradialytic hypotensive and hypoglycaemic episodes experienced by these patients, it was the aim of the present study to evaluate the influence of different dialysate glucose concentrations (5.5 mmol/L or 11 mmol/L) on blood pressure and glycaemic regulation, using special dialysis equipment - the GENIUS System. This cross-over, prospective and randomised study, total duration 14 weeks, included 20 diabetic patients on maintenance haemodialysis. Group 1: 9 patients dialysed using dialysate with a glucose concentration of 5.5 mmol/L and after 7 weeks switched to dialysate with a glucose concentration of 11 mmol/L. Group 2: vice versa. Results show a statistically higher number of patients with hypoglycaemic and hypotensive episodes using dialysate with a 5.5 mmol/L glucose concentration. Also, mean serum glucose values were higher during haemodialysis sessions with a glucose dialysate concentration of 11 mmol/L. There were no statistical differences between the groups in laboratory values, HbA1C, insulin doses or in anthropometric parameters. Our results suggest that fewer diabetic patients undergoing haemodialysis using a higher dialysate glucose concentration of 11 mmol/L have hypoglycaemic and hypotensive episodes. Since this dialysate glucose concentration had no influence on lipid or hepatic metabolism, anthropometric parameters and especially HbA/1C values in this short-term study, the long term examination of its effects is warranted.

Aged↗
PubMed2000

Whither high-dose chemotherapy in breast cancer?

Four trials of high-dose chemotherapy with stem cell support in breast cancer in the adjuvant and metastatic settings have shown no long-term disease-free or overall survival gain. This relative failure of a single high-dose therapy we believe opens up the development of a dose-dense approach with block scheduling as the most promising way forward. This intensive chemotherapy can be more easily combined with the newer biological therapies and our prediction is that this will prove to be the most effective treatment in the future for women with poor risk breast cancer.

Antineoplastic Agents↗
PubMed2000

Autophagic tubes: vacuolar invaginations involved in lateral membrane sorting and inverse vesicle budding.

Many intracellular compartments of eukaryotic cells do not adopt a spherical shape, which would be expected in the absence of mechanisms organizing their structure. However, little is known about the principles determining the shape of organelles. We have observed very defined structural changes of vacuoles, the lysosome equivalents of yeast. The vacuolar membrane can form a large tubular invagination from which vesicles bud off into the lumen of the organelle. Formation of the tube is regulated via the Apg/Aut pathway. Its lumen is continuous with the cytosol, making this inverse budding reaction equivalent to microautophagocytosis. The tube is highly dynamic, often branched, and defined by a sharp kink of the vacuolar membrane at the site of invagination. The tube is formed by vacuoles in an autonomous fashion. It persists after vacuole isolation and, therefore, is independent of surrounding cytoskeleton. There is a striking lateral heterogeneity along the tube, with a high density of transmembrane particles at the base and a smooth zone devoid of transmembrane particles at the tip where budding occurs. We postulate a lateral sorting mechanism along the tube that mediates a depletion of large transmembrane proteins at the tip and results in the inverse budding of lipid-rich vesicles into the lumen of the organelle.

Cytoskeleton↗
PubMed2000

Cell-free reconstitution of microautophagic vacuole invagination and vesicle formation.

Many organelles change their shape in the course of the cell cycle or in response to environmental conditions. Lysosomes undergo drastic changes of shape during microautophagocytosis, which include the invagination of their boundary membrane and the subsequent scission of vesicles into the lumen of the organelle. The mechanism driving these structural changes is enigmatic. We have begun to analyze this process by reconstituting microautophagocytosis in a cell-free system. Isolated yeast vacuoles took up fluorescent dyes or reporter enzymes in a cytosol-, ATP-, and temperature-dependent fashion. During the uptake reaction, vacuolar membrane invaginations, called autophagic tubes, were observed. The reaction resulted in the transient formation of autophagic bodies in the vacuolar lumen, which were degraded upon prolonged incubation. Under starvation conditions, the system reproduced the induction of autophagocytosis and depended on specific gene products, which were identified in screens for mutants deficient in autophagocytosis. Microautophagic uptake depended on the activity of the vacuolar ATPase and was sensitive to GTPgammaS, indicating a requirement for GTPases and for the vacuolar membrane potential. However, microautophagocytosis was independent of known factors for vacuolar fusion and vesicular trafficking. Therefore, scission of the invaginated membrane must occur via a novel mechanism distinct from the homotypic fusion of vacuolar membranes.

Adenosine Triphosphate↗
PubMed2000

Dose-adjusted thrombosis prophylaxis in trauma surgery according to levels of D-Dimer.

In 234 trauma surgery patients, thrombosis prophylaxis with Nadroparin-Calcium low-molecular-weight heparin (LMWH) was adjusted according to levels of D-Dimer. Basic prophylaxis was 2,850 IU per day. If D-Dimer concentrations rose above 2 mg/L after the fourth postoperative (p.o.) day, LMWH was administered twice a day. Color Doppler ultrasound was performed between the fifth and seventh p.o. days. Patients were divided into a high-risk (group 1: hip, femur, or knee replacement surgery, n=102) and a moderate-risk group (group 2: other surgery of the knee, tibia, fibula, or foot, n=132). Group 1 showed significantly higher D-Dimer levels than group 2 (p<0.001). Measurement of D-Dimer on days 2 and 4 p.o. showed a sensitivity of 100% and a specificity of 72.8% in identifying patients at risk (i.e., D-Dimer>2 mg/L after day 4 p.o.). The overall deep vein thrombosis (DVT) rate in group 1 was 3.9%, and the rate of proximal DVT was 1.96%. In group 2, one distal DVT (0.8%) occurred. The results show that D-Dimer is a useful marker to monitor p.o. coagulation activation and to manage LMWH prophylaxis in trauma surgery patients.

Adult↗
PubMed2000

Recombinant anti-carcinoembryonic antigen antibodies for targeting cancer.

Antibodies can be used to target cancer therapies to malignant tissue; the approach is attractive because conventional treatments such as chemo- and radiotherapy are dose limited due to toxicity in normal tissues. Effective targeting relies on appropriate pharmacokinetics of antibody-based therapeutics, ideally showing maximum uptake and retention in tumor and rapid clearance from normal tissue. We have studied the factors influencing these dynamics for antibodies against carcinoembryonic antigen (CEA). Protein engineering of anti-CEA antibodies, in vivo biodistribution models, and mathematical models have been employed to improve understanding of targeting parameters, define optimal characteristics for the antibody-based molecules employed, and develop new therapies for the clinic. Engineering antibodies to obtain the desired therapeutic characteristics is most readily achieved using recombinant antibody technology, and we have taken the approach of immunizing mice to provide high-affinity anti-CEA single-chain Fv antibodies (sFvs) from filamentous bacteriophage libraries. MFE-23, the most characterized of these sFvs, has been expressed in bacteria and purified in our laboratory for two clinical trials: a gamma camera imaging trial using 123I-MFE-23 and a radioimmunoguided surgery trial using 125I-MFE-23, where tumor deposits are detected by a hand-held probe during surgery. Both these trials showed that MFE-23 is safe and effective in localizing tumor deposits in patients with cancer. We are now developing fusion proteins that use the MFE-23 antibody to deliver a therapeutic moiety; MFE-23:: carboxypeptidase G2 (CPG2) targets the enzyme CPG2 for use in the antibody-directed enzyme prodrug therapy system and MFE::tumor necrosis factor alpha (TNFalpha) aims to reduce sequestration and increase tumor concentrations of systemically administered TNFalpha.

Animals↗
PubMed2000

Developmental profile of Sry transcripts in mouse brain.

Transient activation of the gene Sry in the gonadal ridge during a brief period of embryonic development is believed to function as a key signal for sex determination. However, a number of reports suggest that Sry expression is not as restricted in space and time as one would expect if its role was confined to directing male-specific differentiation in the early gonadal anlage. We have previously reported the occurrence of Sry/SRY transcripts in adult murine and human brain. The present communication is concerned with the study of the ontogenetic time course of Sry transcripts in mouse brain as detected by reverse transcription-polymerase chain reaction (RT-PCR). Particular emphasis was placed on the identification of two different forms of Sry mRNA, which can be linear or circular. To this aim, we used specific RT-PCR strategies to distinguish between both. Sry transcripts were found in male brain tissue of all ontogenetic stages investigated. Circular, presumably untranslatable, transcripts were found in embryonic brains of day 11 through 19. In contrast, postnatal Sry transcripts were linear, and thus translatable, and were found in diencephalon, midbrain, and cortex. The change from one transcript form to the other suggests that expression of the Sry gene in mouse brain is developmentally regulated, presumably by a switch in promoter selection. This supports the notion that Sry expression in brain is biologically significant.

Adult↗
PubMed2000

Na(+)-dependent Ca(2+) transport modulates the secretory response to the Fcepsilon receptor stimulus of mast cells.

Immunological stimulation of rat mucosal-type mast cells (RBL-2H3 line) by clustering of their Fcepsilon receptors (FcepsilonRI) causes a rapid and transient increase in free cytoplasmic Ca(2+) ion concentration ([Ca(2+)](i)) because of its release from intracellular stores. This is followed by a sustained elevated [Ca(2+)](i), which is attained by Ca(2+) influx. Because an FcepsilonRI-induced increase in the membrane permeability for Na(+) ions has also been observed, and secretion is at least partially inhibited by lowering of extracellular sodium ion concentrations ([Na(+)](o)), the operation of a Na(+)/Ca(2+) exchanger has been considered. We found significant coupling between the Ca(2+) and Na(+) ion gradients across plasma membranes of RBL-2H3 cells, which we investigated employing (23)Na-NMR, (45)Ca(2+), (85)Sr(2+), and the Ca(2+)-sensitive fluorescent probe indo-1. The reduction in extracellular Ca(2+) concentrations ([Ca(2+)](o)) provoked a [Na(+)](i) increase, and a decrease in [Na(+)](o) results in a Ca(2+) influx as well as an increase in [Ca(2+)](i). Mediator secretion assays, monitoring the released beta-hexosaminidase activity, showed in the presence of extracellular sodium a sigmoidal dependence on [Ca(2+)](o). However, the secretion was not affected by varying [Ca(2+)](o) as [Na(+)](o) was lowered to 0.4 mM, while it was almost completely inhibited at [Na(+)](o) = 136 mM and [Ca(2+)](o) < 0.05 mM. Increasing [Na(+)](o) caused the secretion to reach a minimum at [Na(+)](o) = 20 mM, followed by a steady increase to its maximum value at 136 mM. A parallel [Na(+)](o) dependence of the Ca(2+) fluxes was observed: Antigen stimulation at [Na(+)](o) = 136 mM caused a pronounced Ca(2+) influx. At [Na(+)](o) = 17 mM only a slight Ca(2+) efflux was detected, whereas at [Na(+)](o) = 0.4 mM no Ca(2+) transport across the cell membrane could be observed. Our results clearly indicate that the [Na(+)](o) dependence of the secretory response to FcepsilonRI stimulation is due to its influence on the [Ca(2+)](i), which is mediated by a Na(+)-dependent Ca(2+) transport.

Amiloride↗
PubMed2000

Phosphatidylinositol 4,5-bisphosphate regulates two steps of homotypic vacuole fusion.

Yeast vacuoles undergo cycles of fragmentation and fusion as part of their transmission to the daughter cell and in response to changes of nutrients and the environment. Vacuole fusion can be reconstituted in a cell free system. We now show that the vacuoles synthesize phosphoinositides during in vitro fusion. Of these phosphoinositides, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) are important for fusion. Monoclonal antibodies to PI(4,5)P(2), neomycin (a phosphoinositide ligand), and phosphatidylinositol-specific phospholipase C interfere with the reaction. Readdition of PI(4, 5)P(2) restores fusion in each case. Phosphatidylinositol 3-phosphate and PI(3,5)P(2) synthesis are not required. PI(4,5)P(2) is necessary for priming, i.e., for the Sec18p (NSF)-driven release of Sec17p (alpha-SNAP), which activates the vacuoles for subsequent tethering and docking. Therefore, it represents the kinetically earliest requirement identified for vacuole fusion so far. Furthermore, PI(4,5)P(2) is required at a step that can only occur after docking but before the BAPTA sensitive step in the latest stage of the reaction. We hence propose that PI(4,5)P(2) controls two steps of vacuole fusion.

Membrane Fusion↗
PubMed2000

Nonsquare transfer-matrix technique applied to the simulation of electronic diffraction by a three-dimensional circular aperture

The transfer-matrix methodology is frequently used to deal with elastic scattering problems that require a solution of the Schrodinger or homogeneous Maxwell equations in the continuous part of their spectra. Until now, this technique was limited to representations associated with square transfer matrices. This paper extends the transfer-matrix methodology to enable consideration of general representations associated with nonsquare matrices. The theory is illustrated by the diffraction of a field-emitted electronic beam by a three-dimensional circular aperture. The application focuses on the dependence of the long-range angular spread on the aperture radius, by highlighting the effects of the field-emission tip shape and dimensions.

Journal Article↗
PubMed2000

Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation.

Base deficit is a parameter often used to guide further treatment in acidotic children and is taken as a measure of how "sick" they are. Five children with septic shock are presented who had persisting base deficit after large volume resuscitation with 0.9% saline. Stewart's strong ion theory of acid-base balance is able to quantify the causes of metabolic acidosis and is used to show that our patients had a hyperchloraemic metabolic acidosis. We show how the chloride content of the saline loads given to our patients caused this hyperchloraemia. It is concluded that 0.9% saline and other chloride rich fluids may not be ideal resuscitation fluids; if used, clinicians must be aware of their potential to cause a persistent base deficit.

Acidosis↗
PubMed2000

Clinical applications of phage-derived sFvs and sFv fusion proteins.

Single chain Fv antibodies (sFvs) have been produced from filamentous bacteriophage libraries obtained from immunised mice. MFE-23, the most characterised of these sFvs, is reactive with carcinoembryonic antigen (CEA), a glycoprotein that is highly expressed in colorectal adenocarcinomas. MFE-23 has been expressed in bacteria and purified in our laboratory for two clinical trials; a gamma camera imaging trial using 123I-MFE-23 and a radioimmunoguided surgery trial using 125I-MFE-23, where tumour deposits are detected by a hand-held probe during surgery. Both these trials show MFE-23 is safe and effective in localising tumour deposits in patients with cancer. We are now developing fusion proteins which use MFE-23 to deliver a therapeutic moiety; MFE-23::CPG2 targets the enzyme carboxypeptidase G2 (CPG2) for use in the ADEPT (antibody directed enzyme prodrug therapy) system and MFE::TNF alpha aims to reduce sequestration and increase tumor concentrations of systemically administered TNF alpha.

Clinical Trials as Topic↗
PubMed2000

Radioimmunoguided surgery in colorectal cancer using a genetically engineered anti-CEA single-chain Fv antibody.

In radioimmunoguided surgery (RIGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumor in the operative field. The rapid blood clearance and good tumor penetration of single-chain Fv antibodies (scFv) offer potential advantages over larger antibody molecules used previously for RIGS. A Phase I clinical trial is reported on RIGS with scFv (MFE-23-his) to carcinoembryonic antigen (CEA). Thirty-four patients undergoing surgery for colorectal carcinoma (17 primary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patient with liver metastases of pancreatic carcinoma received 125I-labeled MFE-23-his scFv (125I-MFE-23-his) 24, 48, 72, or 96 h before operation. 125I-MFE-23-his showed biexponential blood clearance with alpha and beta half-lives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surgery with a hand-held gamma detecting probe (Neoprobe Corp.). 125I-MFE-23-his showed good tumor localization; comparison with histology showed overall accuracy of 84%. Highest median ratios for tumor:normal tissue and tumor:blood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases. High levels of radioactivity were found in the kidneys. Five patients had grade 1 fever, and three had a grade 1 rise in blood pressure according to the Common Toxicity Criteria. There was a significant correlation between these ratios and those measured in excised tissues using a laboratory gamma counter (P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injection and operation, the lack of significant toxicity, and the relatively simple production in bacteria make MFE-23-his scFv suitable for RIGS.

Adult↗
PubMed2000

[Effectiveness of radiochemotherapy in esophageal cancers].

AIM: Simultaneous radio-chemotherapy of the inoperable or irresectable oesophagus cancer. METHOD: Thirteen patients with inoperable oesophagus cancer were treated between 1995-98. The therapy was started with intraluminal HDR AL irradiation for the recanalisation of the oesophagus (Dose 8 Gy in 0.5 cm deep, two-three times, one week interval repeated) followed by the percutem megavolt irradiation one week after the last HDR AL session (50 Gy total dose, 5 x 2 Gy/week fractions in 5 week). The chemotherapy was started simultaneously with the percutem megavolt irradiation (three courses Cisplatin-5-Fluorouracil combination, repeated in four weeks intervals). RESULTS: The swallow function has been improved in 7/13 patients with 1-3 Units (Deutsche Gesellschaft für Radio-Onkologie Dysphagical Classification) remained unchanged in 4/13 and it got worse in 2/13 patients 1 and 3 Units, respectively. Side effects: Oesophagitis of different degree occurred in all patients, consecutive transitory dysphagia developed in 9/27 (33.3%) patients. Follow up time: average 14 month (minimum 3 months, maximum 39 month). The duration of the swallow function improvement: average 13 month (minimum 3 month, maximum 39 month). CONCLUSION: The initial results refer to the favourable effect of the palliative radio-chemotherapy at the inoperable oesophageal cancer.

Adult↗
PubMed1999

[Surgical management of reflux disease--laparoscopy: renaissance of fundoplication?].

The importance of the surgical treatment of the gastroesophageal reflux disease have been increased in recent years. After the medical treatment has spread, the minimally invasive procedures were developed. Testing these procedures clinically and applying them on several numbers of patients, the surgical solution has become conspicuous again and the good results proved reason for the existence of the surgical methods that are effective, safe, cost-effective and load to limited complications. The goal of this article is to sum up the advance of the antireflux-surgery, to give a summary about the tendencies of surgical therapies and representating the new results on this topic.

Fundoplication↗
PubMed1999

Taking engineered anti-CEA antibodies to the clinic.

There is a need to improve on existing targeting technologies in order to develop effective cancer therapy. We have investigated this for colorectal cancer using antibodies directed against carcinoembryonic antigen (CEA). Chemical and molecular protein engineering has been used to produce antibody molecules which differ in molecular weight, affinity, valency and specificity. These have been characterised and tested in animal tumour models and clinical trials to test the parameters important for optimising tumour penetration, increasing residence time in viable areas of the tumour, accelerating clearance from normal tissues and improving therapeutic efficacy.

Animals↗