Biomedical subjects

G Varga

Publications and source records attributed to G Varga.

At least 37 records · Page 2Linked to original sources

PubMed2000

Control of SIV rebound through structured treatment interruptions during early infection.

In a randomized controlled trial with acute simian immunodeficiency virus (SIV)-infected macaques, both highly active antiretroviral therapy (HAART) and HAART with fixed-schedule structured treatment interruption (STI-HAART; alternating 3 weeks on and 3 weeks off therapy) suppressed viral load. In the STI-HAART group, T cell virus-specific immune response (VIR) and control of viral rebound increased concurrently during subsequent interruptions. In contrast, VIR did not increase and SIV rebounded after permanent treatment withdrawal in all animals on continuous HAART. Fixed-schedule STI-HAART appears to be an effective alternative to continuous HAART for the early treatment of retroviral infection.

Adenine↗

PubMed2000

[Detection of minimal residual diseases in B-cell tumors using PCR specific for the immunoglobulin heavy chain gene].

In B-cell non-Hodgkin's lymphomas (NHL), clonal rearrangement of the immunoglobulin heavy chain (IgH) gene provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To explore clinical usefulness of polymerase chain reaction (PCR) analysis of clonal IgH gene rearrangement in the detection of MRD a follow up study of 10 patients with B-cell NHL have been performed. At the time of diagnosis, tumor DNAs were PCR-amplified using sense primer specific for the heavy chain variable region (VH) and antisense primer specific for the heavy chain joining region (JH) of the IgH gene. The clonal rearrangement of IgH gene detected by PCR was used as clonal marker to determine MRD after treatment. In three cases, where clinical remission was not achieved, clonal IgH gene rearrangement was detected after the treatment. In seven cases, clinical remission was achieved after induction therapy but the PCR analysis revealed clonal IgH gene rearrangement in three of the cases. In all of the three cases, where MRD was detected by PCR, clinical relapse developed after 7-28 months of the therapy. In all cases that have relapsed, the IgH gene rearrangement was identical at the time of initial diagnosis and at the relapse. This study demonstrates that PCR analysis of clonal IgH gene rearrangement is a useful method to monitor and detect MRD before clinical relapse.

Biomarkers, Tumor↗

PubMed2000

[Recent advances in the classification and treatment of myelodysplastic syndrome].

The French-American-British (FAB) classification for myelodysplastic syndromes (MDS) is widely accepted in the clinical practice. However, advances in medical science in recent years have prompted some alterations to this purely morphological classification. In the comprehensive new classification four categories are distinguished, such as I. Primary MDS, II. MDS with myeloproliferative features, III. Mutagen induced (secondary) MDS and IV. MDS with hereditary predisposition. Treatment of MDS patients is nowadays stratified according to age of patient, availability of an HLA-identical sibling donor and risk assignment. Therapeutic strategies have been inspired by either missionary approaches converting premalignant cells into normal behaviour or by crusader tactics destroying non-compliant elements at the expense of innocent bystanders. Since apoptosis appears to be final pathway by which the hematopoietic cells undergo premature cell death, reversal of apoptosis would be the principal goal in the missionary treatment. The rational approach to suppress apoptosis would either aim at eliminating inducers of apoptosis or at preventing apoptosis by the administration of factors that can shift the balance to cell survival. Intensive acute leukemia-type treatment studies showed complete remission rates varying from 15% to 64%. The prolonged cytopenia leads to high early death rate. Transplantation of allogeneic stem cells has proven to be the only curative treatment option, but the expense of considerable transplant related mortality. The elaboration of risk adapted treatment algorithms has been much facilitated by the publication of the International Prognostic Scoring System (IPSS), which uses marrow blast percentage, cytogenetic data and number of cytopenias to delineate low, intermediate (1 and 2) and high risk categories.

Animals↗

PubMed2000

[Psychosomatic dermatologic symptoms].

The explanations of the psychosomatic dermatological symptoms are based on the dysfunction of the emotional and autonomic nervous system. In the first instance the dermatological symptoms of psychic origin are examined by the general practitioner, than the dermatologist and finally after negative findings--the psychiatrist. Behind the non-improving, itching and scratched eczema sometimes was found either Ekbom-syndrome (often diagnosed as gerontological delusions of parasitosis) or therapy-resistant allergy (which conceals depression). The authors present condensed case--stories (about delusions of parasitosis and allergic syndromes) proving the excellent results achieved using citalopram and in the case of Ekbom-syndrome--risperidone therapy.

Aged↗

PubMed2000

[Larynx-preserving pharyngoesophagectomy in the treatment of cancer of the pharyngoesophageal junction].

UNLABELLED: Pharyngo-laryngo-esophagectomy has been the sole surgical option in the management of advanced tumors arising from the pharyngoesophageal junction. This operation is associated with high morbidity, mortality and poor quality of life due to loss of larynx. The aim of the author was to achieve a reduction in tumor size by means of neoadjuvant chemoradiotherapy and so to make the tumor amenable to a larynx preserving operation avoiding pharyngo-laryngo-esophagectomy. Between 1. January 1998 and 31. December 1999, 11 consecutive patients with advanced cancer of pharyngo-esophageal junction were treated with neoadjuvant chemoradiotherapy (carboplatin, 5-fluorouracil, 30-35 Gy telecobalt irradiation). The tumor regressed in all cases and moreover, in 6 patients a larynx preserving pharyngo-esophagectomy could be carried out. This operation consists of total esophagectomy, resection of posterior pharynx wall and Akiyama-type gastric pull up with side-to-side pharyngo-gastrostomy. All 6 patients recovered. In 2 cases after neoadjuvant therapy the tumor disappeared from the cervical esophagus and so that a pharyngo-laryngectomy and free jejunum transfer could be performed. 3 other patients remained irresectable due to lymph node metastases. CONCLUSION: Larynx preserving pharyngo-esophagectomy is a safe operation by means of which the larynx can be preserved even in those patients whose tumor is located at the level of pharyngo-esophageal junction, on the posterior wall of the pharynx.

Aged↗

PubMed2000

[Correlation of alcohol consumption and pancreatitis in Hungary].

Alcoholic etiology of acute pancreatitis is outstanding high in Hungary. The aim of this retrospective study was to analyse the etiology of patients of 5 years. Between 1990 and 1994 altogether 374 patients were admitted with acute pancreatitis, which is three and half times higher than between 1970 and 1974. From the 374 cases 220 had alcoholic and only 115 had biliary etiology. Altogether in 127 patients developed necrosis, the rate of alcoholic etiology was 80% in this subgroup. During the last two decades the trend of alcohol consumption became one of the most burning question in Hungary. Based on the Jellinek's formula alcohologists estimate the number of alcoholics more than one million. The number of pancreatitis related death multiplied almost four times between 1970 and 1994. The doubling of alcohol consumption was practically simultaneous with the increase of morbidity and mortality of pancreatitis. Hungary shows the most disfavourable distribution of drink varieties among the high-consuming countries in Europe.

Acute Disease↗

PubMed1999

Effect of deramciclane, a new 5-HT receptor antagonist, on cholecystokinin-induced changes in rat gastrointestinal function.

Recent studies suggested that serotonin receptors may be involved in modulating the actions of cholecystokinin (CCK) in the gastrointestinal tract. The present work was designed to compare the effects of deramciclane, a recently developed serotonin-2 (5-HT2A/2C) receptor antagonist, and lorglumide, a CCK(A) receptor antagonist, on exogenous and endogenous CCK-induced pancreatic enzyme secretion and pancreatic growth, as well as on the emptying of the stomach and the gallbladder. Pancreatic secretory function was tested while CCK release was evoked by diversion of bile-pancreatic juice in rats. Adaptive growth of the pancreas was induced by chronic intragastric administration of camostate, a potent synthetic trypsin inhibitor in rats. Gastric emptying of a noncaloric test meal was investigated in response to intraduodenal intralipid infusion, also in rats. In fasted mice, gallbladder emptying was examined in response to intragastric egg yolk administration. In rats, diversion of bile-pancreatic juice from the duodenum stimulated pancreatic amylase secretion. This action was blocked by deramciclane and by lorglumide. Pancreatic hypertrophy and hyperplasia induced by chronic camostate administration was also suppressed by both the serotonin- and the CCK-receptor antagonists. Intraduodenal administration of intralipid induced a significant delay in gastric emptying. This effect was inhibited by both deramciclane and lorglumide in rats. In mice, intragastric administration of egg yolk elicited an accelerated release of bile from the gallbladder. Prior treatment with either deramciclane or lorglumide abolished this response. Lorglumide was able to inhibit the functional responses elicited by exogenous CCK administration in both pancreas, stomach and gallbladder, while deramciclane was not effective under such circumstances. Our data show that deramciclane inhibited the effects of CCK on pancreatic, gastric and gallbladder function when its endogenous release was stimulated, but did not alter the effects of exogenously administered peptide. These results suggest that serotonin, primarily via 5-HT2A receptors, may modulate CCK-mediated gastrointestinal functions in rats.

Animals↗

PubMed1999

Secretion from minor salivary glands following ablation of the major salivary glands in rats.

Since minor salivary glands are tiny and dispersed, ductal cannulation cannot be used when studying their function. The present study was devised to develop a method of measuring minor salivary gland function by excision of the major glands. Female rats (230-280 g) were anaesthetized with sodium pentobarbital. Ablation of the submandibular, sublingual and parotid glands was performed through a sagittal neck incision. Sham-operated rats served as controls. Groups of sialadenectomized animals were investigated immediately and after 1 week, 2 weeks and 3 months. To study secretory function, the mouth was rinsed with 250 microl water in every 5 min and protein and amylase concentrations were measured. After an initial 50 min of basal secretion pilocarpine (1 mg/kg, i.p.) was given. Bilateral ablation of both submandibular, sublingual and parotid glands led to a moderate loss of body weight and a considerable increase in water intake. No other obvious abnormality was observed for periods up to 90 days following surgery. We deduce that the minor glands secrete approximately 14 % of protein and 1% of amylase in whole saliva Secretion is maintained even after 90 days following removal of the major glands. Surgical removal of the major salivary glands allows the secretory function of the minor glands in rats to be studied in vivo.

Amylases↗

PubMed1999

Nitric oxide modulates salivary amylase and fluid, but not epidermal growth factor secretion in conscious rats.

The involvement of the L-arginine/NO pathway in the control of salivary fluid, amylase and epidermal growth factor (EGF) secretion was investigated in conscious rats. For the collection of saliva, an oesophageal cannula was implanted. To obtain steady secretion, submaximal carbachol background infusion was given. Different treatments included NO synthase inhibitor N(G)-nitro-L-arginine (NOLA; with or without phentolamine, propranolol), L-arginine, D-arginine and NO donor 3-morpholinosydnonimine (SIN-1) administration. Volume, amylase activity and EGF output in the secreted fluid were determined in 30 min mixed saliva samples. Carbachol infusion alone produced a modest, sustained salivary fluid and amylase secretion. NOLA (30 mg/kg) further increased both fluid (p<0.001) and amylase outputs (p<0.001). These latter effects were prevented by L-arginine but not by D-arginine or by phentolamine. Propranolol administration decreased both fluid and amylase secretion below the carbachol plateau, and NOLA did not modify this suppressed secretory rate. SIN-1 did not alter either volume or amylase secretion. Interestingly, NOLA given without carbachol did not modify salivation. Neither carbachol nor NOLA changed salivary EGF output. The present results suggest that the L-arginine/NO pathway has a modulatory role in the cholinergic control of salivary amylase secretion, but not in EGF output. The mechanisms of inhibitory action of NO on salivary fluid and amylase secretion remain to be identified.

Amylases↗

PubMed1999

Molecular mechanisms of T lymphocyte activation: convergence of T cell antigen receptor and IL-1 receptor-induced signaling at the level of IL-2 gene transcription.

Co-stimulation of murine EL-4 thymoma cells-carrying high numbers of TCR and type I IL-1 receptors (IL-1R)-with anti-CD3 antibodies and IL-1 resulted in synergistic enhancement of IL-2 synthesis. While the extracellular signal-regulated kinase (ERK) cascade was activated by both receptors, IL-1 preferentially stimulated Jun-N-terminal kinases (JNK) and p38 mitogen-activated kinase or microtubule-associated protein kinase (MAPK). Interruption of TCR- or IL-1R-stimulated ERK cascade by PD-98059, a specific inhibitor of MAP/ERK kinase (MEK), resulted in partial suppression of nuclear factor of activated T cells activation and in complete inhibition of IL-1-stimulated NFkappaB activation. Suppression of activation of both MEK and p38 MAPK resulted in significant inhibition of IL-2 gene expression. The results show that maximal activation of the IL-2 gene requires activation of at least two different protein kinase cascades, i.e. of the ERK and p38 pathways but presumably also that of JNK which converge at the level of the IL-2 promoter resulting in enhancement of its transcriptional activity.

Animals↗

PubMed1999

Expression of aquaporin 1 (AQP1) water channels in human labial salivary glands.

Aquaporin (AQP) water channels are widely expressed in the membranes of fluid-transporting epithelia. Despite the fact that salivary glands are the site of considerable water movement, relatively little is known about the role of aquaporins in human salivary glands. We have examined the expression of AQP1 in human parotid, sublingual and labial salivary glands. Total RNA was extracted from glandular tissue obtained from surgery or biopsy. The presence of AQP1 mRNA was demonstrated in each of the three glands by RT-PCR using primers specifically designed for human AQP1. The PCR product from the labial gland RNA was further amplified with nested primers and the sequence confirmed by automated fluorescent DNA sequencing. The cleaned first PCR product from these glands was then used as a 32P-labelled hybridization probe in a Northern analysis which confirmed the presence of significant amounts of AQP1 transcript in all three glands. AQP1 expression was also demonstrated in cryosections of human labial glands by immunohistochemistry using peroxidase-linked antibodies. Antibody labelling was most prominent in the capillaries but was also evident in the basal regions of the labial gland acini, and may therefore be associated with the serous demilunes which are believed to be a significant site of fluid movement.

Adult↗

PubMed1999

Membrane stretch and salivary glands - facts and theories.

Cell shape in salivary glands is affected by mechanical forces. In the acini and ducts cell shape is modified by the contractions of the myoepithelial cells in both the secretory and ductal portions of the glands. At the organ level shape changes are due to muscle contraction during mastication, food intake and speech. All these factors may cause some degree of stretching of salivary cell membranes. Recent studies suggest that physical forces influence signal transduction, gene expression, secretory function, cell differentiation and proliferation. Here we overview membrane stretch-activated cellular events. Evidence from a variety of tissues suggests that mechanical forces may alter the properties of acinar cells leading to cytoskeletal reorganisation, changes in ion fluxes, modulation of secretory activity and subsequent release of transmitters such as ATP. Transmitters released from acinar cells may modulate the secretory activity of salivary tissue, and interact with classical regulatory pathways.

Adenosine Triphosphate↗

PubMed1999

Management of corrosive injuries of the esophagus.

During a 5-year period from 1993 to 1998, 22 cases of caustic esophageal injuries were referred to our clinic, caused by acid consumption as suicidal intentions or as an accident. Four out of 10 cases where acute exploration was performed the corrosion was so extended that no further intervention could be done, and all of them died within 24 hours. In the remaining 6 cases acute esophagogastrectomy, or total gastrectomy with esophageal exclusion was performed. Three out of 6 patients survived primary surgery, who later underwent esophageal reconstruction with a colon substitute. In 12 patients no indication for acute surgery arose, but later during the follow-up in 5 of them dysphagia and corrosive stricture developed. All underwent successful esophageal reconstruction with colon substitute. Case reports, acute management, indications for surgery and prognostic factors are also discussed.

Adult↗

PubMed1999

Effect of laparoscopic antireflux operation on esophageal manometry, 24 hours pH-metry and quality of life in gastroesophageal reflux disease.

It has been suggested that laparoscopic Nissen fundoplication is an effective procedure for the treatment of gastroesophageal reflux disease (GERD). Twenty-six patients with chronic gastroesophageal reflux disease underwent laparoscopic floppy Nissen fundoplication. 24 hours pH-metry, manometry and Gastrointestinal Quality of Life Index (GIQLI) questionnaire were done preoperatively, six-month and one year after the operation. The six weeks control investigation was limited to 24 pH-metry and GIQLI interview. Adequate reflux control was obtained in all patients, with reduction in acid reflux variables at six weeks, six months as well as at one year after the operation. Preoperative reflux index and DeMeester score was significantly higher than those we found postoperatively at both time period. Preoperative lower esophageal sphincter tone and length was abnormal on average. Both parameters increased significantly at six-month and one year after the operation. GIQLI also showed characteristic changes. Compared to preoperative values we found significantly higher GIQLI at both six-month and one year following surgery. Laparoscopic Nissen fundoplication provides an excellent symptomatic and physiologic outcome in patients with esophageal reflux disease.

Data Interpretation, Statistical↗

PubMed1998

[Surgical trauma induced by laparoscopic cholecystectomy].

The objective demonstration of improved postoperative recovery suggests that surgical injury induced by the laparoscopic approach is less intense than that after open surgery. Forty-two patients diagnosed as having noncomplicated gallstones were studied prospectively. They were operated on by laparoscopy (LC, n = 21) or open surgery (OC, n = 21). Both surgical procedures induced significant changes of investigated parameters (acute-phase response, free radical mediated reactions, neutrophil functions). Comparison of the results of the two cholecystectomy techniques showed that laparoscopic cholecystectomy induced a significantly less intense acute-phase response, a more attenuated oxidative stress characterising by free radical mediated reactions and that is less disruptive to neutrophil function. The results and the data from the literature suggest that surgical injury causing by the laparoscopic cholecystectomy is less intense than that after open cholecystectomy, which can explain partially the better clinical outcome following laparoscopic versus open procedure.

Cholecystectomy↗

PubMed1998

Cloning of a new Kunitz-type protease inhibitor with a putative transmembrane domain overexpressed in pancreatic cancer.

In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel putative transmembrane protein with two Kunitz-type serine protease inhibitor domains. The identified gene named kop (Kunitz domain containing protein overexpressed in pancreatic cancer) was assigned to chromosome 19 in the region 19q13.1. Kop was detected at high levels in pancreatic cancer cell lines and was overexpressed in pancreatic cancer tissues as compared to both, normal pancreas and chronic pancreatitis tissues. Being a member of the Kunitz-type serine protease inhibitor family, this new gene may participate in tumour cell invasion and metastasis and in the development of the marked desmoplastic reaction typical for human pancreatic cancer tissues. In this context, the fact that kop has a putative transmembrane domain may have functional implications of particular interest.

Adenocarcinoma↗

PubMed1998

Longitudinal monthly body measurements from 1 to 12 months of age: a study by practitioners for practitioners. Zurich Association of Practicing Paediatricians.

UNLABELLED: A longitudinal growth study with monthly measurements during the 1st year of life was conducted by nine paediatricians working in private practice in Zurich. Of 92 children, none was lost to the study and only 32 of 1104 planned visits were missed; the quality of the measurements was comparable to that of a specialised university clinic. Compared to the Zurich Longitudinal Growth Studies, children of this study were considerably heavier and taller. In 92% of the subjects, growth velocity was at least once outside the reference range (3rd 97th percentile). For weight increments, the corresponding proportion was 87%. CONCLUSIONS: The data indicate that current standards for the 1st year of life for the Zurich area might no longer be appropriate and need to be updated. The currently used velocity percentiles based on 3-monthly measurements are not suitable to assess individual height and weight increments calculated from monthly measurements.

Anthropometry↗

PubMed1998

Role of different bombesin receptor subtypes mediating contractile activity in cat upper gastrointestinal tract.

Mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) are known to increase the motility of different segments in the gut. The present study was carried out to identify the bombesin receptor subtypes mediating the contractions induced by exogenous bombesin-like peptides in muscle strips isolated from cat esophagus, fundus, and duodenum. Both GRP-10 and NMB evoked concentration-dependent contractions in circular strips of esophagus and fundus and in longitudinal strips of the duodenum. These contractions were tetrodotoxin- and atropine-resistant. The potency of NMB in esophageal strips was 33 times higher than that of GRP-10. The NMB-preferring receptor antagonists D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2 (SSocta) and D-Nal-cyclo[Cys-Tyr-D-Trp-Orn-Val-Cys]-Nal-NH2 (BIM-23127) shifted the NMB and GRP concentration-response curves to the right, while the GRP-preferring receptor antagonist [D-Phe6]Bombesin(6-13)-methyl-ester (BME) did not affect the response to the peptides. Isolated muscle strips from the cat fundus and duodenum showed a higher sensitivity to GRP-10 than to NMB. In both segments, BME shifted the GRP-10 and NMB concentration-response curves to the right, while SSocta had no effect. The antagonism of BME was competitive on duodenal but not competitive on fundic muscle. We conclude that the direct myogenic action of GRP-10 and NMB in the esophagus is mediated mainly via NMB-preferring receptors, while GRP-preferring receptors are responsible for the contractile responses to bombesin-like peptides in feline fundus and duodenum. Our data suggest that the GRP receptor population located on fundic muscle might be nonhomogeneous.

Animals↗