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Biomedical subjects

A Lazar

Publications and source records attributed to A Lazar.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Ruptured pseudoaneurysm of the splenic artery. A complication of chronic pancreatitis].

HISTORY AND FINDINGS: A pale looking 33-year-old man with a history of perforated gastric ulcer and pancreatitis with surgically drained pseudocyst was admitted because of painless anal bleeding. Heart rate was 100/min, blood pressure 90/60 mm Hg. INVESTIGATIONS: Haemoglobin concentration (6.3 g/dl) and RBC count (2.4 mill./microliters) indicated anaemia due to bleeding. Sonography and computed tomography demonstrated chronic calcifying pancreatitis and thrombosis of splenic and mesenteric veins. There were grade 1 oesophageal varices on endoscopy. The source of bleeding was found by coloscopy to be a submucous pulsating tumour in the region of the left flexure, which on angiography was an aneurysm of the splenic artery. TREATMENT AND COURSE: The pseudoaneurysm of the splenic artery, which had perforated into the colon, was resected together with a partial pancreas excision and splenectomy. There were no complications and the patient was discharged symptom-free after 15 days, and there had been no further bleeding 6 months later. CONCLUSION: Pseudoaneurysm of a visceral artery is a rare, but life-threatening, complication of pancreatitis. Treatment options are operation and/or interventional catheter embolisation.

Adult↗
PubMed1996

[Long-term observation of patients with biopsy proven myocarditis or dilated cardiomyopathy].

Dilated cardiomyopathy (DC) and myocarditis (MCD) are still cardiac diseases of unknown etiology and pathogenesis. Due to uncertain natural history of MCD also treatment remains controversial. We observe long-term outcome of 30 pts with biopsy-proved MCD (group I) and 25 pts with DC (group II). The diagnosis of MCD was established on Dallas criteria of MCD. Almost all pts presented symptoms of congestive heart failure. All group I pts were treated with immunosuppressive agents: azathioprine 1.5 mg/kg/d and prednisone with initial dose of 1.5 mg/kg/d. After tapering off 0.75 mg/kg/d of prednisone and initial dose of azathioprine were given up to 6 months. All pts obtained digitalis, diuretics, ACEI, antiarrhythmic drugs if necessary. We studied the survival and clinical status (NYHA class) of treated pts. Clinical improvement was observed in 93% of pts with MCD within 6 months, but 20% of pts deteriorated within the next 6 months. Almost all pts survived 1 year. Out of 30 pts with MCD, 16 pts remain in lower NYHA class (NYHA I-II) between 26 and 69 months of follow-up. Within the group II (DC) 28% of pts died in the first year of observation. Out of 15 pts in 14 pts advanced chronic heart failure (NYHA III-IV) is presented in the end of observation. Echocardiographic parameters of pts with congestive heart failure and biopsy-proved MCD or DC did not differ significantly. We observed correlation between improvement of the LV echocardiographic parameters and improvement of clinical status of treated pts.

Adolescent↗
PubMed1995

Allosteric modulation of acetylcholinesterase activity by peripheral ligands involves a conformational transition of the anionic subsite.

Replacement of residues Asp74, Trp286, and Tyr72, which are constituents of the peripheral anionic site (PAS) of human acetylcholinesterase (HuAChE), affected similarly both the binding and the inhibition constants of the PAS-specific ligand propidium, demonstrating that changes in the inhibitory activity are a direct consequence of altered binding to the PAS. In contrast, the active center HuAChE mutants W86A and Y133A show respective 350- and 25-fold increased resistance to inhibition by propidium but no change in binding affinities, demonstrating that the allosteric mechanism of PAS-mediated inhibition involves a conformational change of these Trp86 and Tyr133 residues rather than physical obstruction of substrate access by the inhibitor itself. These findings support the recent proposal that the allosteric mechanism operates via transition between active and nonactive conformations of the anionic subsite Trp86 and that replacement of Tyr133 by alanine may stabilize a nonactive Trp86 conformation that occludes the active center [Ordentlich et al. (1995) J. Biol. Chem. 270, 2082]. In further support of this mechanism and the role of Tyr133, we find that (a) the dissociation constants (Kd) for the noncovalent complexes of the irreversible inhibitors diisopropyl phosphorofluoridate or paraoxon with Y133A HuAChE are increased 20-500-fold, relative to either wild-type enzyme or its Y133F or W86A mutants; and (b) access of substrates such as 3,3-dimethylbutyl thioacetate is restored by removal of Trp86 from the Y133A enzyme (i.e., the W86A/Y133A mutant). We suggest that the conformational transition of Trp86 is coupled to the motions of the cysteine loop (Cys69-Cys96) of HuAChE and is inherent to the dynamics of the native enzyme.

Acetylcholinesterase↗
PubMed1995

[Narrow-lumen mesocaval interposition shunt in liver cirrhosis and recurrent esophageal varices hemorrhage. Standard surgery of the future in failure of sclerotherapy?].

In a prospective study, conducted between 1.1.1987 and 31.12.1992, 72 consecutive patients (50 men, 22 women; mean age 59.8 [16-72] years) with cirrhosis of the liver and recurrent bleeding from oesophageal or fundal varices, were treated with a mesocaval interposition shunt, made of reinforced Goretex 10 or 12 mm in diameter. Further selection criteria were Child-Pugh class A (n = 39) or B (n = 33), liver volume (by ultrasound) between 1000 and 2500 ml, portal vein perfusion index of at least 10% and histological exclusion of activity or progression of the cirrhosis. Four patients (5.6%) died during the first 30 days after the intervention, and four had recurrent bleeding from the varices, three of them during the postoperative period, one during the second postoperative year. The cumulative shunt patency rate was 94.4% (up to 84 months). An acute encephalopathy occurred in six patients (8.3%), which was successfully treated with protein restriction and neomycin administration. Intra- and post-operative hemodynamic investigation confirmed maintenance of portal-vein perfusion in all patients, but there was a significant tendency towards reduction after 3 years in all patients. The overall survival rate after 7 years was 75%, with 85% for patients in Child-Pugh class A and 65% for those in class B. The results indicate that the described method can achieve satisfactory portal decompression with maintenance of portal-vein flow. It is especially suitable as a standard method if sclerotherapy has failed.

Adolescent↗
PubMed1995

Mesocaval interposition shunt with small-diameter polytetrafluoroethylene grafts in sclerotherapy failure.

Fifty-seven patients with failed sclerotherapy received a mesocaval interposition shunt with an externally supported, ringed polytetrafluoroethylene prosthesis of either 10 or 12 mm diameter. Thirty-one patients had Child-Pugh grade A disease and 26 grade B; all had a liver volume of 1000-2500 ml. Follow-up ranged from 16 months to 6 years 3 months. Three patients (5 per cent) died in the postoperative period. There were two postoperative recurrences of variceal haemorrhage and one recurrent bleed in the second year after surgery. The cumulative shunt patency rate was 95 per cent and the incidence of encephalopathy 9 per cent; the latter was successfully managed by protein restriction and/or lactulose therapy. The actuarial survival rate for the whole group at 6 years was 78 per cent, for those with Child-Pugh grade A 88 per cent and for grade B 67 per cent. Small-lumen mesocaval interposition shunting achieves portal decompression, preserves hepatopetal flow, has a low incidence of shunt thrombosis, prevents recurrent variceal bleeding and is not associated with significant postoperative encephalopathy.

Anastomosis, Surgical↗
PubMed1995

Extended liver-specific functions of porcine hepatocyte spheroids entrapped in collagen gel.

The potential use of porcine hepatocytes in a bioartificial liver device requires large quantities of viable and highly active cells. To facilitate the scaling up of the system, liver specific activities of hepatocytes should be maximized. One way of enhancing the specific activities is to cultivate hepatocytes as multicellular spheroids. Freshly isolated porcine hepatocytes form spheroids when cultivated in suspended cultures. These spheroids exhibit higher activities for a number of liver specific functions compared to hepatocytes cultivated as monolayers. However, these activities decreased in a few days in culture. Entrappment of spheroids in collagen gel sustained their metabolic activities at a stable level over 21 days. Production of albumin and urea by spheroid hepatocytes entrapped in collagen gels were 2 to 3 times higher than those by freshly isolated single cells. P-450 activity was demonstrated by metabolism of lidocaine to its main metabolite, monoethylglycinexylidide. Phase II drug metabolism was demonstrated by glucuronidation of 4-methylumbelliferone. This work shows that porcine hepatocyte spheroids entrapped in collagen maintain differentiated functions for an extended time period. Such hepatocyte spheroid entrappment system may facilitate the development of a bioartificial liver support device.

Albumins↗
PubMed1995

[The value collateralization and venous obstruction operations in acute bleeding esophageal varices in patients with cirrhosis of the liver].

Despite the development of new techniques and the great successes in recent years in Japan, the value of surgical venous obstruction in the treatment of oesophageal and gastric variceal bleeding remains controversial. For this reason we chose to evaluate our own results over a period of 10 years. Splenectomy is the only curative operation that eliminates the local portal hypertension in peripheral thrombosis of the splenic vein. Transposition of the spleen to the thoracic cavity with establishment of splenopulmonary anastomoses is indicated in the case of prehepatic block in childhood. The most widespread and successful of the operations to achieve venous obstruction are extended oesophagogastric disconnection (devascularisation with selective proximal vagotomy and fundoplication) as introduced by our group; para-oesophagogastric devascularisation and oesophageal transection according to Johnston using the clip suture device; and devascularisation of the upper two-thirds of the stomach and half of the abdominal oesophagus with transection, splenectomy and pyloroplasty after Sugiura and Futagawa. In the 10-year period analysed, we operated on 90 patients with acute bleeding oesophageal varices, many of them as emergencies. 66% were classified as Child-Pugh type C. Early mortality amounted to 26% (n = 24), and the morbidity rate was 42%. The 5- and 10-year survival rates were 50% and 38% respectively with regular endoscopic follow-up and repeat sclerotherapy. In an emergency, the choice between a shunt operation and a venous obstruction procedure depends on the individual case and the surgeon's experience.(ABSTRACT TRUNCATED AT 250 WORDS)

Collateral Circulation↗
PubMed1994

Acetylcholinesterase peripheral anionic site degeneracy conferred by amino acid arrays sharing a common core.

Several of the residues constituting the peripheral anionic site (PAS) in human acetylcholinesterase (HuAChE) were identified by a combination of kinetic studies with 19 single and multiple HuAChE mutants, fluorescence binding studies with the Trp-286 mutant, and by molecular modeling. Mutants were analyzed with three structurally distinct positively charged PAS ligands, propidium, decamethonium, and di(p-allyl-N-dimethylaminophenyl)pentane-3-one (BW284C51), as well as with selective active center inhibitors, hexamethonium and edrophonium. Single mutations of residues Tyr-72, Tyr-124, Glu-285, Trp-286, and Tyr-341 resulted in up to 10-fold increase in inhibition constants for PAS ligands, whereas for multiple mutants up to 400-fold increase was observed. The 6th PAS element residue Asp-74 is unique in its ability to affect conformation of both the active site and the PAS (Shafferman, A., Velan, B., Ordentlich, A., Kronman, C., Grosfeld, H., Leitner, M., Flashner, Y., Cohen, S., Barak, D., and Ariel, N. (1992) EMBO J. 11, 3561-3568) as demonstrated by the several hundred-fold increase in Ki for D74N inhibition by the bisquaternary ligands decamethonium and BW284C51. Based on these studies, singular molecular models for the various HuAChE inhibitor complexes were defined. Yet, for the decamethonium complex two distinct conformations were generated, accommodating the quaternary ammonium group by interactions with either Trp-286 or with Tyr-341. We propose that the PAS consists of a number of binding sites, close to the entrance of the active site gorge, sharing residues Asp-74 and Trp-286 as a common core. Binding of ligands to these residues may be the key to the allosteric modulation of HuAChE catalytic activity. This functional degeneracy is a result of the ability of the Trp-286 indole moiety to interact either via stacking, aromatic-aromatic, or via pi-cation attractions and the involvement of the carboxylate of Asp-74 in charge-charge or H-bond interactions.

Acetylcholinesterase↗
PubMed1994

Current therapeutic strategy in bleeding esophageal varices in babies and children and long-term results of endoscopic paravariceal sclerotherapy over twenty years.

71 consecutive babies and children with bleeding esophageal varices managed primarily by emergency or elective paravariceal endoscopic sclerotherapy (PES) have been reviewed and followed up for twenty years. In 36 of them 53 different operations to prevent further variceal hemorrhage had been performed without permanent success. In 50 children (70 per cent--Group Ia), portal vein obstruction, in 2 (3 per cent--Group Ib), congenital hepatic fibrosis and in 19 (27 per cent--Group II) babies and children different types of cirrhoses were the cause of portal hypertension. Emergency PES was necessary for 29 and successful for 28 children (96.5 per cent). Recurrent bleeding in one child stopped after introduction and inflation of the Sengstaken-Blakemore tube. In one case an urgent transthoracic esophageal resection and fundoplication was performed because of recurrent hemorrhage in spite of repeated PES. 6 children--3 foreigners--were lost to follow-up after 3, 5, 6, 7, 11 and 12 years. Under regular PES there were 3 rebleedings (4 per cent) during the first month managed successfully by PES or conservatively; another 3 rebleedings (4 per cent) occurred during the first year. In "sclerotherapy failures" (recurrent hemorrhage in spite of chronic PES in 6 children aged more than 10 years 6 elective and selective shunts were carried out 3, 5, 6, 8, 10 and eleven years after the first PES. The number of complications was high, but the vast majority was asymptomatic and no complications was responsible for death. There was no death in children with portal vein obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Massive and recurrent gastrointestinal hemorrhage due to jejunal varices in an afferent loop--diagnosis and management.

Bleeding from "ectopic" varices outside the gastroesophageal region is an uncommon complication of portal hypertension. Although the high mortality rate of bleeding duodenal varices has been emphasized (1-4), an awareness of the condition and its characteristic presentation may enable diagnostic and therapeutic procedures to be performed rapidly with an increased likelihood of a successful outcome. This report describes a patient with recurrent, frequent and massive hemorrhage from jejunal varices in the afferent loop after a Billroth II resection, chronic pancreatitis and portal hypertension; the diagnosis and management of this unusual case of recurrent gastrointestinal bleeding are discussed.

Adult↗
PubMed1994

Microfocal myocardial lesions in cardiac allograft recipients.

Endomyocardial biopsy has been widely accepted as a method for diagnosing acute heart transplant rejection. However, disperse and microfocal changes due to a smaller specificity, cause difficulty in histological differential diagnosis. The purpose of the present study was to morphologically assess microfocal lesions, to determine their relative incidence and their specificity in relation to the time of onset after cardiac transplantation and to compare these data with those concerning more extensive changes. We examined 658 samples in 152 endomyocardial biopsies obtained from 45 posttransplant patients, including 311 samples identified as containing focal lesions of varying size, and 33 as containing diffuse lesions. Samples with focal and diffuse lesions (344 samples) were submitted for further studies which revealed that microfocal changes in the transplanted heart show more enhanced polymorphism in the composition of cellular infiltrates than more extensive changes. Furthermore they are frequently seen in biopsies in the first two months after transplantation and as single changes. Necrosis and cellular infiltrates at that time are more diversified than those seen in later biopsies. In our experience differential diagnosis of microfocal myocardial lesions in cardiac allograft recipients is difficult. Potentially microfocal lesions may be a result not only of acute rejection but also a result of myocardial alterations in the course of intensive therapy both in the donor and in the recipient, cold ischemia, reperfusion, and inflammation. The morphological picture in some cases is not sufficient to make an unequivocal diagnosis. This indicates the need for improvement of diagnostic methods and criteria on the one hand, and a suitable approach to the problem on the other hand. Our experience shows that a temporary solution could be establishing of a separate classification category for these types of changes and defining them as nonspecific microfocal lesions.

Biopsy↗
PubMed1994

Histologic analysis of myocardial biopsies from donor hearts before transplantation.

Myocardial biopsy is an accepted diagnostic tool in the assessment of acute heart transplant rejection. An important element of this assessment is the so-called zero (0) biopsies. The purpose of the present study was histologic analysis and comparison of these biopsies. We examined biopsy specimens obtained from 35 hearts of donors aged 15-46 years. 0-1 biopsy was obtained during organ procurement and 0-2 biopsy immediately before coronary reperfusion after implantation. Histologic analysis of changes was carried out by two observers. 0 biopsies in 8 out of 35 cases were histologically normal. In 23 cases minute histologic changes were found. They included myocyte enlargement, perinuclear vacuolization, interstitial and perivascular edema and fibrosis. Sporadically (4 cases) we encountered also signs of cardiac myocyte damage (microfocal necrosis and/or myocyte disruption). Differences were seen both between individual donors as well as 0-1 and 0-2 biopsies obtained from the same donor. 0-1 and 0-2 biopsies differed more clearly in the appearance of interstitium and microvessels. Interstitial edema was more frequent in 0-2 than in 0-1 biopsy and it was usually more severe. Differences between 0-1 and 0-2 biopsies with respect to changes in cardiac myocytes and interstitium were as expected and may result from progress of changes due to hypoxia. In contrast, endothelial swelling was more frequent and more severe in 0-2 than in 0-1 biopsies. This phenomenon may be accounted for by easier penetration and greater effect of perfused preservation solutions on endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Evaluation of anchorage-dependent cell propagation systems for production of human acetylcholinesterase by recombinant 293 cells.

Production of recombinant human acetylcholinesterase (AChE) by a high producer human embryonic kidney cell line (293) was evaluated by three main cell propagation systems; surface propagator, fixed-bed reactor and stirred microcarrier cultures. The recombinant cell line expresses AChE levels as high as 10-20 mg/l/day. System productivities in either the surface propagator (multitray system), or in the fixed-bed reactor (polyurethane macroporous sponges) were 4-8 mg AChE/l/day during a production period of 8 days. Similar productive rates, yet longer production periods (up to 22 days), were obtained in microcarrier (MC) cultures using either polystyrene beads (Biosilon); collagen-coated dextran beads (Cytodex-3); or gelatin macroporous beads (Cultispher-G). Best results were obtained in an aggregate culture using cellulose beads charged with diethylaminoethyl (DEAE) groups, (Servacel), as carriers. In this culture, a system productivity of 6-10 mg/l/day was maintained for 28 days.

Acetylcholinesterase↗
PubMed1993

[Single hepatocellular carcinoma (phi < or = 5 cm) in liver cirrhosis. Early diagnosis and surgical removal].

721 patients with liver cirrhosis were regularly screened by sonography and determination of alpha fetoprotein during a period of eleven years (1.1.1982-1.1.1993). In 137 of them hepatocellular carcinoma (HCC) was diagnosed; 28 (20.4%) had a unilocular HCC with a diameter up to 5 cm. Diagnosis was regularly verified by sonographic guided puncture, in rare cases by laparoscopy and biopsy. Beside a diameter of 5 cm the tumor should be localized at least 5 mm from the main structures in the hilus, and not in the centre of the liver; furthermore multilocular hepatocellular carcinomas and intra- and extrahepatic metastases were contraindications. Child-Pugh-classification should be A+B and urea synthesis rate at least 6 g per day. In 21 patients (75%) a portal hypertension was diagnosed; 19 (68%) had bled from esophageal varices; in case of one bleeding a therapeutic sclerotherapy and in case of recurrent variceal hemorrhage an elective shunt operation were performed. Surgical resection was carried out with controlled hypotension and temporary occlusion of the hepatoduodenal ligament. Tumor was removed by segmentectomy or bisegmentectomy and in rare cases by enucleation. There were 3 clinical deaths (10.7%); causes of death were liver failure and (2) sepsis (1). All patients could be followed up to January 1, 1993; there were 12 further deaths of liver failure, tumor recurrence or second tumor. 13 patients are still living. Thus the live expectancy for one year was 80, for 5 years 50 and for 10 years 30%. There is no doubt, that it is possible to detect hepatocellular carcinoma in patients with liver cirrhosis early by regular sonography and determination of alpha-fetoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Production and secretion of high levels of recombinant human acetylcholinesterase in cultured cell lines: microheterogeneity of the catalytic subunit.

To allow for structural analysis of the human acetylcholinesterase (hAChE) subunit, a series of eukaryotic vectors was designed for efficient expression. Several eukaryotic multicistronic expression vectors were tested in various mammalian cell lines. All expression vectors contained the selectable neo gene under control of a weak promoter, while the hAChE cDNA was under control of the cytomegalovirus (CMV) immediate-early or Rous sarcoma virus long terminal repeat (RSV LTR) or simian virus 40 (SV40) early promoters. Optimal production and secretion of recombinant hAChE (rehAChE) was achieved in the embryonal kidney 293 cell line transfected either with the RSV-hAChE or with CMV-hAChE expression vectors. Clones expressing and secreting as much as 5-25 pg of enzyme per cell per 24 h were obtained without resorting to coamplification techniques or continuous maintenance of cells under selective pressure. The purified (specific activity of 6000 units per mg protein) homodimer and tetramer enzyme molecules displayed typical AChE biochemical properties: a Km value of 120 microM for acetylthiocholine; a kcat value of 3.9 x 10(5)/min, and selective by AChE-specific inhibitors. Catalytic subunit dimers (130 kDa) exhibit differential N-glycosylation patterns, and upon reduction resolve into 67- and 70-kDa monomeric subunits. These two forms appear as a single discrete 62-kDa band following deglycosylation by N-glycanase. The N-terminal amino acid sequence analysis of the purified mature enzyme suggests the existence of two alternative cleavage sites for the removal of the signal peptide, in which the 'mature' position 1 is either Ala31 or Gly33. Both of these positions conform with the consensus signal peptide recognition sequences and demonstrate bidirected processing of signal peptides on a native molecule.

Acetylcholinesterase↗
PubMed1991

The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant.

Site-directed mutagenesis was used to study the cysteine residue involved in the assembly of human acetylcholinesterase (HuAChE) catalytic subunits. Substitution of the cysteine at position 580 by alanine resulted in impairment of interchain disulfide bridge formation; the mutagenized enzyme (C580A) was secreted from recombinant cells in the monomeric form and failed to assemble into dimers. The mutant monomeric HuAChE did not differ from the native oligomeric enzyme neither in rate of catalysis nor in affinity to acetylthiocholine. Mutant monomers were also shown to retain the acetylcholinesterase characteristic sensitivity to high substrate concentrations. The mutation did not seem to affect the efficiencies of either synthesis or secretion of recombinant HuAChE polypeptides, as was demonstrated in cell lines derived from human embryonic kidney (293 cells) as well as from a human neuroblastoma (SK-N-SH). Furthermore, the mutation did not lead to an increase in accumulation of intracellular HuAChE polypeptides, suggesting that export of acetylcholinesterase from cells may not be coupled to subunit assembly.

Acetylcholinesterase↗