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A Lazar

Publications and source records attributed to A Lazar.

At least 19 recordsLinked to original sources
PubMed2006

Extraneuronal monoamine transporter and organic cation transporters 1 and 2: a review of transport efficiency.

The extraneuronal monoamine transporter (EMT) corresponds to the classical steroid-sensitive monoamine transport mechanism that was first described as "uptake2" in rat heart with noradrenaline as substrate. The organic cation transporters OCT1 and OCT2 are related to EMT. The three carriers share basic structural and functional characteristics. Hence, EMT, OCT1 and OCT2 constitute a group referred to as non-neuronal monoamine transporters or organic cation transporters. After a brief general introduction, this review focuses on the critical analysis of substrate specificity. We calculate from the available literature and compare consensus transport efficiency (clearance) data for human and rat EMT, OCT1 and OCT2, expressed in transfected cell lines. From the plethora of inhibitors that have been tested, the casual observer likely gets the impression that these carriers indiscriminately transport very many compounds. However, our knowledge about actual substrates is rather limited. 1-Methyl-4-phenylpyridinium (MPP+) is an excellent substrate for all three carriers, with clearances typically in the range of 20-50 microl min(-1) mg protein(-1). The second-best general substrate is tyramine with a transport efficiency (TE) range relative to MPP+ of 20%-70%. The TEs of OCT1 and OCT2 for dopamine, noradrenaline, adrenaline and 5-HT in general are rather low, in the range relative to MPP+ of 5%-15%. This suggests that OCT1 and OCT2 are not primarily dedicated to transport these monoamine transmitters; only EMT may play a significant role in catecholamine inactivation. For many substrates, such as tetraethylammonium, histamine, agmatine, guanidine, cimetidine, creatinine, choline and acetylcholine, the transport efficiencies are markedly different among the carriers.

1-Methyl-4-phenylpyridinium↗
PubMed2005

Dermal absorption of permethrin following topical administration.

OBJECTIVE: Permethrin is an insecticide used in the treatment of lice and scabies infections. Although its efficacy and safety have been well documented, pharmacokinetic data are sparse. The objective of this study was to determine the systemic exposure of permethrin and the duration of residence in the human body following topical administration. METHODS: The study consisted of three parts. In six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg permethrin (cis/trans: 25/75) was administered to the hair of the head. In another six young healthy men (part 2) and in six male or female scabies patients (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, and its conjugates was measured using a gas chromatography/electron capture detection method. RESULTS: Pharmacokinetics were similar in all study parts. The time of maximal urinary excretion rate was 12.3, 20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was well tolerated. CONCLUSIONS: The extent of systemic exposure following external therapeutic administration of permethrin is very low compared with doses used for preclinical toxicity studies, and elimination is virtually complete after 1 week. These data provide the pharmacokinetic basis for the clinical safety of topical permethrin.

Administration, Topical↗
PubMed2005

Full thickness skin graft for nail unit reconstruction.

A retrospective study of 13 patients assessed the use of a full thickness skin graft for nail unit reconstruction after total nail unit removal for nail bed malignancies. No failures of the graft were observed and no patient had recurrence of the malignant tumour at 4 year follow-up. Full thickness skin grafting is a simple procedure which provides a good cosmetic outcome and does not produce significant donor site morbidity.

Adolescent↗
PubMed2004

Multiple organ failure due to 5-fluorouracil chemotherapy in a patient with a rare dihydropyrimidine dehydrogenase gene variant.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the metabolism of the chemotherapeutic drug 5-fluorouracil (5-FU). Application of 5-FU is restricted by a narrow therapeutic index because of severe toxicity of WHO grades III-IV. The exon 14-skipping mutation (c.1905+1G>A) accounts for approximately a quarter of all severely toxic cases. However, numerous other polymorphisms have been identified within the DPYD gene in affected patients, and the pathophysiological significance of most of them is unclear. PATIENT AND METHODS: We report a patient with advanced caecum cancer who twice received 950 mg 5-FU and 45 mg folinic acid as adjuvant by bolus injection. 2 days after onset of chemotherapy, the patient developed a multiple organ dysfunction exhibiting a cardiogenic shock with severe left ventricular insufficiency, marked reduction of renal function, and beginning hepatic encephalopathy with somnolence, myoclonus, and a seizure. In order to investigate a possible defect within the DPYD gene direct sequencing of all 23 exons was carried out. RESULTS: Genotyping revealed a rare c.1601G>A polymorphism which causes a change in the protein sequence (S534N). Data regarding the clinical relevance are ambiguous. The polymorphism has been detected together with an intronic mutation and both polymorphisms have consistently been reported with reduced enzyme activity. CONCLUSION: The present case provides further evidence of an etiologic role of the c.1601G>A mutation for DPD deficiency and the occurrence of severe 5-FU-related toxicity and underlines the value of comprehensive pharmakogenetic diagnostics with respect to the dihydropyrimidine dehydrogenase.

Adenocarcinoma↗
PubMed2004

CYP1A1 alleles in women with focal nodular hyperplasia of the liver (FNH).

OBJECTIVE: Disorders of steroid hormone metabolism might be related to the etiology of focal nodular hyperplasia of the liver (FNH), a benign tumor, especially prevalent in women. The cytochrome P450 1A1 (CYP1A1) enzyme is implicated in the bioactivation of multiple precarcinogens as well as in the metabolism of steroids. Genetic polymorphisms of CYP1A1 have been associated with altered catalytic activity in the hydroxylation of sex hormones and this may account for interindividual variability in exposure to hormone-mediated cell proliferation signals and reactive steroid metabolites. In the study at hand, we aimed to evaluate a possible association between CYP1A1*1, *2A, *2B, and *4 alleles and FNH. METHOD: Genotyping of 26 affected female patients of Caucasian origin was carried out using PCR/RFLP. RESULTS: Allele frequencies for the CYP1A1 variants *2A, *2B and *4 in 26 female patients with FNH were 0.058, 0.019 and 0.058, respectively. Crude odds ratios for the individual alleles were 0.75 (95% CI 0.23-2.44), 0.72 (95% CI 0.10-5.34) and 1.96 (95% CI 0.59-6.50), respectively. There were no significant differences between these values and corresponding allele frequencies obtained in a large German sample of unaffected Caucasian women. CONCLUSION: The present data do not suggest a relevant association between CYP1A1 polymorphisms and focal nodular hyperplasia of the liver in female Caucasians.

Adult↗
PubMed2003

Expression of the hyaluronan receptor RHAMM in endometrial carcinomas suggests a role in tumour progression and metastasis.

PURPOSE: Interactions of hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) have been proposed as being important in promoting tumour progression and dissemination. This comparative study was designed to investigate the RHAMM expression patterns in endometrial carcinoma. METHODS: We examined a series of 89 endometrial carcinomas and 15 normal endometrial tissues by immunohistochemistry, using a RHAMM-specific polyclonal antibody. Expression of RHAMM was assessed according to the pattern and intensity within (overall cytoplasm, center/periphery of tumours) and between the tumours. The staining results were compared to the corresponding clinical data (age, menopause status, histological staining, histological grading, lymph node status). RESULTS: RHAMM-expression was detectable in 58% of the 89 tumours [Histological stage: pT1a (8/12); pT1b (16/37); pT1c (18/26); pT2 (6/9); pT3a (4/5)] and 13% (2/15) of the normal endometrial tissues. The positivity rates for RHAMM were 100% in patients with positive lymph nodes but only 50.7% in patients with negative lymph nodes ( P<0-01). Additionally, the expression pattern showed a highly significant correlation ( P<0.01) with the histological grade of the tumours [G1 (6/42), G2 (33/34), G3 (13/13)] and occurrence of lymph node metastases. CONCLUSIONS: Our results suggest that RHAMM expression may enhance and improve the invasion and metastasis of endometrial carcinomas.

Adenocarcinoma, Clear Cell↗
PubMed2001

Protein-calixarene interactions: complexation of Bovine Serum Albumin by sulfonatocalix[n]arenes.

The complexation of Bovine Serum Albumin with sulfonatocalix[n]arenes has been demonstrated by means of electrospray mass spectrometry, dynamic light scattering and atomic force microscopy; with sulfonatocalix[4]arene one strong and two weaker binding sites are detected; the effects on the structure of thin films formed by surface deposition of BSA show that the sulfonatocalix[n]arenes act to reticulate the films and produce essentially planar systems.

Animals↗
PubMed2000

Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II.

Structures of recombinant wild-type human acetylcholinesterase and of its E202Q mutant as complexes with fasciculin-II, a 'three-finger' polypeptide toxin purified from the venom of the eastern green mamba (Dendroaspis angusticeps), are reported. The structure of the complex of the wild-type enzyme was solved to 2.8 A resolution by molecular replacement starting from the structure of the complex of Torpedo californica acetylcholinesterase with fasciculin-II and verified by starting from a similar complex with mouse acetylcholinesterase. The overall structure is surprisingly similar to that of the T. californica enzyme with fasciculin-II and, as expected, to that of the mouse acetylcholinesterase complex. The structure of the E202Q mutant complex was refined starting from the corresponding wild-type human acetylcholinesterase structure, using the 2.7 A resolution data set collected. Comparison of the two structures shows that removal of the charged group from the protein core and its substitution by a neutral isosteric moiety does not disrupt the functional architecture of the active centre. One of the elements of this architecture is thought to be a hydrogen-bond network including residues Glu202, Glu450, Tyr133 and two bridging molecules of water, which is conserved in other vertebrate acetylcholinesterases as well as in the human enzyme. The present findings are consistent with the notion that the main role of this network is the proper positioning of the Glu202 carboxylate relative to the catalytic triad, thus defining its functional role in the interaction of acetylcholinesterase with substrates and inhibitors.

Acetylcholinesterase↗
PubMed2000

Experience with percutaneous dilational tracheostomy.

Percutaneous dilational tracheostomy (PDT) has gained popularity among critical care specialists in the past 10 years. The initial studies in our specialty resulted in essentially banning the procedure as a dangerous substitute for standard operative tracheostomy. Despite this action, more than 1,100 cases of percutaneous tracheostomy have been reported with details on complications. We reviewed all published data and studied 311 patients of our own. A prospective study was performed in 3 groups of patients: 1) 50 patients scheduled for PDT performed in the operating room by a head and neck surgeon (group 1); 2) 50 patients who underwent standard operative tracheostomy performed by the same surgeon (group 2); and 3) 211 patients who underwent bedside PDT by critical care physicians (group 3). The intraoperative complication rates were 0% in group 1, 2% in group 2, and 4% in group 3; the postoperative complication rates were 13%, 4%, and 12%, respectively. There were 2 deaths in group 3, and none in groups 1 or 2. The statistically significant differences among the groups were the superiority of group I over group 3 in intraoperative complications, as well as the lower postoperative complication rate of the standard tracheostomy group. These results show that PDT can be performed with acceptable morbidity rates in relation to published complication rates of standard tracheostomy, but it has no advantage over standard tracheostomy with respect to postoperative morbidity. When they are performed by a head and neck surgeon, the morbidity associated with both standard and percutaneous tracheostomies can be reduced.

Adult↗
PubMed2000

Varieties of long-term outcome among patients in psychoanalysis and long-term psychotherapy. A review of findings in the Stockholm Outcome of Psychoanalysis and Psychotherapy Project (STOPP).

This paper reports the main findings of a large-scale study of subsidized psychoanalysis and long-term psychotherapy. More than 400 people in various phases, before, during and after subsidized psychoanalysis or long-term psychodynamic psychotherapy, were followed up for a period of three years with personal interviews, questionnaires and official statistics. Our analyses revealed progressive improvement the longer patients were in treatment--impressively strong among patients in psychoanalysis--on self-rating measures of symptom distress and morale. Improvement, however, was equally weak in both groups on a self-rating measure of social relations. Dosage factors (treatment duration and session frequency in combination) partly accounted for the outcome differences between those referred to psychoanalysis and those referred to long-term psychotherapy. Attitudes and ideals among therapists and analysts concerning the goals and means of psychotherapy were also associated with patient outcome, although in rather complex ways. A significant part of the outcome differences between patients in psychoanalysis and in psychotherapy could be explained by the adoption, in a large group of therapists, of orthodox psychoanalytic attitudes that seemed to be counterproductive in the practice of psychotherapy but not in psychoanalysis. It is suggested that this effect may be a negative transfer of the psychoanalytic stance into psychotherapeutic practice and that this may be especially pronounced when the attitudes are not backed up by psychoanalytic training.

Adult↗
PubMed2000

[Small unilocular hepatocellular carcinoma (0 < 5 cm) in patients with liver cirrhosis. Early diagnosis, surgical indications, resection and prognosis].

In 151 (17.5%) of 861 patients with liver cirrhosis regularly screened by sonography and determination of alpha-fetoprotein a hepatocellular carcinoma (HCC) was detected. Diagnosis was verified by sonographically guided fine needle puncture and exceptionally by laparoscopy and direct puncture. In 34 patients (22.5%) selection criteria for operation were a tumour diameter under 5 cm, no central localisation in the liver and at least 5 mm distant from the main structures; furthermore multilocular HCC and intra- and extrahepatic metastases were contraindications. Additionally Child-Pugh-classification should be A + B and urea synthesis rate 6 g per day. 27 patients (80%) had esophagogastric varices seen at endoscopy and 20 (59%) had bleeding episodes from varices managed endoscopically or surgically. Types of surgical resections were segmentectomy [17], bisegmentectomy [10] and oncologically defined wedge resections [7] using controlled hypotension and interrupted occlusion of the hepatoduodenal ligament. 4 patients (11.8%) died within 30 days of liver failure [3] and sepsis [1]. All patients could be followed up for eleven years: 18 patients died after 1.5-10 years of liver failure, tumour recurrence or second tumour and a cause not associated with HCC, 12 patients are living. Kaplan-Meier survival curves show that survival at 5 years is 50% and at 10 years 34%. The main indicators for a good prognosis were clinically the HBsAG-activity, the Child-Pugh-classification and the application of autologous blood, pathologic-anatomically the classification and grading and histologically the absence of vascular invasion, absence of satellites and a number of mitoses under 7 in the visual field. For tumour recurrence dysplasia is of positive influence.--Liver resection remains the most widely used therapeutic option for treatment of HCC in cirrhosis. The early and long-term results can be improved by early diagnosis, strict selection of patients for operation and the use of well defined clinical, pathological and histological criteria.

Aged↗
PubMed1999

The absolute number of circulating CD34+ cells as the best predictor of peripheral hematopoietic stem cell yield.

Many controversies still exist about the timing of leukapheresis procedures for PBSC transplantation. Thirty-nine patients were followed daily by monitoring the absolute PB WBC count and CD34+ cell enumeration prior to apheresis. These determinations were compared with the apheresis cell content (nucleated cells and CD34+ cells yield). There was a highly significant correlation between PB CD34+ cells and apheresis CD34+ cell yield (r = 0.921, p < 0.001). A small but significant correlation was found between the PB WBC count and the apheresis nucleated cell content (r = 0.383, p < 0.001), but no correlation was found between PB WBC count and apheresis CD34+ cell yield (r = -0.065, p = 0.460). A target value of 20 x 10(6) CD34+ cells/L was determined to be the most reliable predictor to collect at least 1.0 x 10(6) CD34+ cells/kg in a single apheresis. Of the 39 patients, 20 could be followed after transplantation, and a good correlation was found for total number of CD34+ cells reinfused and platelet and neutrophil engraftment. No correlation was found for nucleated cells infused and engraftment. CD34+ cell determination is a better predictor than WBC count for timing leukapheresis and is thus recommended for monitoring the quality of the product.

Adolescent↗
PubMed1998

Analysis of factors affecting outcome after hepatectomy of patients with liver cirrhosis and small hepatocellular carcinoma.

OBJECTIVE: To review our policy of screening patients at risk of developing hepatocellular carcinoma (HCC), and to present 10 years' experience of hepatic resection for small HCC (< 5 cm). DESIGN: Retrospective study. SETTING: Teaching hospital, Germany. SUBJECTS: 861 patients with hepatic cirrhosis and oesophageal varices of whom 151 (18%) had HCC confirmed histologically; 30 of these tumours (20%) were less than 5 cm in diameter and suitable for resection. INTERVENTIONS: Segmentectomy (n = 14) bisegmentectomy (n = 10), and oncologically defined wedge resection (n = 6). MAIN OUTCOME MEASURES: Mortality, morbidity, and survival. RESULTS: 4 patients died within 30 days of liver failure and sepsis (n = 20, liver failure (n = 1), and bronchopneumonia (n = 1). The main beneficial prognostic factors were Child classification, donation of autologous blood, and an encapsulated tumour. The main indicators of a poor prognosis were invasion of the liver, venous invasion, invasion of the resection margin, and the presence of microsatellite tumours and nodules. 12 of the 26 survivors developed recurrences during the first five years postoperatively (46%). Kaplan-Meier survival curves showed that survival at 1 year was 80%, at 3 years 65%, and 5 years 50%, and at 10 years 30%. CONCLUSION: Hepatic resection is a useful treatment for small HCC, but its success depends on early detection and careful selection of patients.

Aged↗
PubMed1998

Ambiguity of morphological criteria of myocarditis in cardiac biopsy specimens.

Myocarditis is diagnosed when leukocytic infiltrate is accompanied by myocyte degeneration or necrosis. Endomyocardial biopsy is evaluated as the main diagnostic method. The purpose of the present study was to examine the individual elements of a histological picture and specify morphological criteria of diagnosing myocarditis in cardiac biopsy. The Dallas criteria were the point of reference. In the cardiobiopsies from 70 patients with clinically suspected myocarditis or congestive cardiomyopathy an active myocarditis was found in 19 cases, significantly more frequently in the group clinically classified as having myocarditis. Contraction bands, endocardial changes and vasculopathy were more frequent in cases histologically classified as active myocarditis than in borderline myocarditis. In our opinion the Dallas criteria include certain ambiguities concerning mainly differences of individual types and phases of myocarditis as well as their relations to congestive cardiomyopathy. The sensitivity and specificity of the diagnosis are related both to methodological limitations (material selection) and difficulties occurring mainly at the level of perception, evaluation and interpretation of changes. It is possible to improve the efficacy of cardiac biopsy in diagnosing myocarditis if a new techniques better revealing myocyte damage and more unequivocally determining the cellular composition of the stroma have been developed.

Adolescent↗
PubMed1997

[Telling the bad news: do the elderly want to know their diagnoses and participate in medical decision making?].

In view of reported changes in western countries in the preferred model of doctor-patient relations, we evaluated the wishes of elderly persons for open doctor-patient communication with regard to terminal disease. Data was collected in 1994 from 987 elderly persons (70+) by structured interviews. Most of respondents wanted open communication and wished to be involved in medical decisions regarding life-sustaining treatment. However, only a minority tell their physicians and/or family members of their wishes. This suggests that most of the elderly expect physicians to be the first to initiate discussions of these issues. The results also indicate that among the elderly, those more educated, less religious, and those living in Israel longer, are more likely to want open communication with their physicians. This is explained by the relationship of these characteristics with the dominant cultural values of this group, and its acceptable models of relations in other areas of life.

Aged↗
PubMed1997

Isosorbide nitrates, nitroglycerin, and sodium nitroprusside induce vasodilation concomitantly with inhibition of carbonic anhydrase I in erythrocytes.

This study describes the relationship between nitroglycerin, isosorbide dinitrate, sodium nitroprusside, and carbonic anhydrase I, as well as the involvement of this carbonic anhydrase I in vasodilation. Two groups of coronary patients and a group of rabbits underwent treatment with the above-mentioned vasodilating drugs. The activity of red blood cell carbonic anhydrase was monitored and determined by the stopped-flow method. The results show that these drugs inhibit the activity of the isozyme in parallel to their vasodilating effect. The results of this study lead to the hypothesis that through the pH modifications induced by these vasodilators by the inhibition of carbonic anhydrase I, the isozyme may be involved in the regulation of vascular tonus.

Animals↗