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Biomedical subjects

D Lucas

Publications and source records attributed to D Lucas.

At least 73 records · Page 4Linked to original sources

High-performance liquid chromatographic determination of chlorzoxazone and 6-hydroxychlorzoxazone in serum: a tool for indirect evaluation of cytochrome P4502E1 activity in humans.

Chronic alcohol consumption is known to induce the enzyme cytochrome P4502E1 (CYP2E1), which is involved in the toxicity and carcinogenicity of a number of solvents and xenobiotics. It was recently suggested that in vivo chlorzoxazone metabolism could be a potential tool as a non-invasive probe for measuring CYP2E1 activity in humans. Therefore, a simple and sensitive method was developed for the determination of chlorzoxazone and its major metabolite 6-hydroxychlorzoxazone in both serum and urine. Biological samples were hydrolysed by Helix pomatia juice, deproteinized with perchloric acid, and then extracted using ethyl acetate. The compounds were separated by high-performance liquid chromatography on an octadecylsilane column with a mobile phase of acetonitrile-0.5% acetic acid in water (30:70, v/v) and detected at 287 nm. The linearity of the method was tested in the concentration range 0.5-20 micrograms/ml, and the limit of detection in biological samples was found to be 0.5 microgram/ml. Within- and between-run precision was below 5% and 10%, respectively, for both compounds at three concentrations (0.5, 10 and 20 micrograms/ml). The accuracy of the procedure was in the range 0.3-6%. Serum levels and urinary excretion of chlorzoxazone and its metabolite were studied in five healthy controls and five alcoholic patients, following oral administration of 500 mg of chlorzoxazone. The concentration ratio 6-hydroxychlorzoxazone/chlorzoxazone in blood was shown to be a valuable tool for the evaluation of CYP2E1 activity in humans.

Administration, Oral↗

Comparison of levels of cytochromes P-450, CYP1A2, CYP2E1, and their related monooxygenase activities in human surgical liver samples.

Hepatic microsomal cytochromes P-450 CYP1A2, and CYP2E1 contents and catalytic activities have been simultaneously investigated in 42 patients undergoing diagnostic liver biopsy. CYP1A2 contents, measured by Western blotting, were correlated with methoxyresorufin-O-demethylation and ethoxyresorufin-O-deethylation (r = 0.65 and r = 0.66, p < 0.001, respectively). CYP2E1 contents were correlated with 1-butanol oxidation and 6-hydroxylation of chlorzoxazone (r = 0.75 for both, p < 0.001). CYP1A2 catalytic activities varied by 30- to 40-fold, whereas CYP2E1 activities varied by 6- to 20-fold. In our study, these variations were not related to liver diseases or cancer of the digestive tract nor to alcohol drinking or smoking habits, because patients were alcohol- and tobacco-free for 1 month before the study. Other environmental factors, diet habits, and/or genetic factors could explain the large interindividual variations observed.

Adult↗

Sterility of refrigerated injectable collagen syringes after injection of patient.

BACKGROUND: Injectable collagen has been used for more than 15 years to correct soft tissue cosmetic defects. After injection, the collagen remaining in the syringe is often refrigerated for later use in the same patient, despite manufacturer and Food and Drug Administration recommendations to discard the unused collagen. OBJECTIVE: This study examined the incidence of bacterial contamination of stored collagen. METHODS: Syringe needle tips and collagen from 50 previously used syringes containing either Zyderm I, Zyderm II, or Zyplast were cultured separately under aerobic and anaerobic conditions. Bacterial isolates were identified. RESULTS: Propionibacterium acnes was cultured from 7 of 50 needle tips. One positive needle tip culture grew both P. acnes and Staphylococcus aureus. Bacteria were isolated from only one collagen sample that grew a nonhemolytic streptococcus that may have represented a laboratory contaminant. CONCLUSION: Syringes of collagen stored for repeated use rarely become contaminated with bacteria despite frequent contamination of their needle tips. Skin abscesses after collagen injection should be cultured under anaerobic, as well as aerobic, conditions so that infections caused by P. acnes will not be missed.

Collagen↗

Preoperative embolization of the spleen in children with hypersplenism.

Splenomegaly associated with myelodysplastic disorders in children may be massive and can result in pancytopenia, abdominal discomfort, and respiratory distress. When these symptoms cannot be relieved by nonsurgical means, splenectomy may be indicated. Under such conditions, surgical splenectomy carries increased risks, as the thrombocytopenia is difficult to correct secondary to splenic sequestration. Additionally, the surgical anatomy is often distorted secondary to the massive spleen and dissection can be difficult. These factors can lead to uncontrollable hemorrhage. In an attempt to decrease intraoperative blood loss, the authors successfully performed preoperative splenic artery embolization in 11 of 12 children (age range, 1-11 years) with pancytopenia due to hypersplenism. Hypersplenism requiring surgical splenectomy was due to leukemia (n = 9), myelodysplastic syndrome (n = 1), immune thrombocytopenia (n = 1), and osteopetrosis (n = 1). Embolization was performed under general anesthesia, prior to surgery, with gelatin sponge particles alone, Gianturco coils alone, or a combination of polyvinyl alcohol sponge particles and Gianturco coils. Embolization allowed for safe surgical splenectomy.

Child↗

Enzymatic production of acetaldehyde from ethanol in rat brain tissue.

The capacity for the brain to produce acetaldehyde (AcHO) from ethanol was determined in rat brain homogenates. Rat brains were perfused with saline-heparin solution and homogenized in a phosphate buffer. Varying amounts of tissue were incubated with ethanol (0-100 mM) for periods of up to 60 min. The reaction was stopped by the addition of desferrioxamine and ice-cold perchloric acid. Supernatants were treated with dinitrophenylhydrazine reagent, extracted with isooctane in the presence of an internal standard, and the derivatives were separated by HPLC. The addition of 4-methyl pyrazole (an alcohol dehydrogenase inhibitor) or metyrapone (a cytochrome P450 inhibitor) had no effect on the amount of recovered AcHO. On the other hand, treatment with the catalase inhibitors sodium azide, cyanamide, or 3-amino-1,2,4-triazole blocked the production of AcHO while the addition of exogenous peroxide or a peroxide-generating system enhanced the production of AcHO. Overall, these results suggest that AcHO may be produced in the brain during alcohol intoxication, through the action of the enzyme catalase.

Acetaldehyde↗

Differences in hepatic microsomal cytochrome P-450 isoenzyme induction by pyrazole, chronic ethanol, 3-methylcholanthrene, and phenobarbital in high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats.

High and low alcohol sensitivity (HAS and LAS) rats have been selected for their differences in ethanol-induced sleep time. Liver monooxygenase activities were studied in HAS and LAS rats before and after treatments with known inducers such as chronic ethanol, pyrazole, 3-methylcholanthrene (3-MC) and phenobarbital (PB) to determine whether the selection procedure also selected for differences in the cytochrome P-450 (P-450) inducibility. This previously has been shown with long sleep (LS) and short sleep (SS) mice, which were selected using a similar criterion. 3-MC and PB, in conjunction with chronic ethanol treatment, were used in order to evaluate the interactions of ethanol with these inducers. Prior to treatment, total P-450 content was slightly lower in LAS than in HAS rats. However, both lines displayed the same microsomal monooxygenase activities related to different P-450 isozymes. This was demonstrated by ethoxyresorufin deethylation (EROD) for cytochrome P-450 1A1 (CYP1A1), acetanilide hydroxylation (ACET) for CYP1A2, pentoxyresorufin dealkylation (PROD) for CYP2B, 1-butanol oxidation (BUTAN) and N-nitrosodimethylamine demethylation (NDMA) for CYP2E1. After the different treatments, HAS rats did not differ from LAS rats in their CYP2E1 inducibility. However, pyrazole, PB and 3-MC treatment led to differences in CYP1A and CYP2B monooxygenase activities between the two lines. The enhancement of PROD by pyrazole treatment was less prominent in LAS (1.7-fold of the control value) than in HAS rats (3.8-fold).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

Effects of [N-(L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (SCH32615), a neutral endopeptidase (enkephalinase) inhibitor, on levels of enkephalin, encrypted enkephalins and substance P in cerebrospinal fluid and plasma of primates.

In halothane-anesthetized and -ventilated cynomologus macaque monkeys, the effects of administering vehicle (n = 3) or the neutral endopeptidase inhibitor N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (16 mg/kg, n = 5; or 100 mg/kg, n = 3, intravenously) was examined. Cisternal CSF aliquots were examined by radioimmunoassay: 1) for Met enkephalin; 2) after trypsin and carboxypeptidase B treatment for encrypted enkephalin (X-ENK); 3) for substance P; and 4) for unmetabolized drug. Similar measures were carried out in femoral artery and femoral venous plasma, except that substance P was not assayed. In CSF, prior to drug, low, but measurable levels of enkephalin (61 pg/ml), X-ENK (285 pg/ml) and substance P (16 pg/ml) were observed. Vehicle-injected animals showed no change from baseline levels over a 4-hr sampling period in either plasma or CSF levels. In contrast, following 16 mg/kg, in CSF, there was a significant 9-fold increase in MET and 11-fold increase in X-ENK at 30 min. CSF-substance P levels rose also by a factor of 2, with the peak effect observed at 60 min. All levels displayed a significant reduction by 4 hr. There was no statistical difference between the maximum effects observed with either the 16- or 100-mg/kg dose. Plasma peptide levels of enkephalin and X-ENK were not altered by drug. CSF displayed significant drug levels by 30 min, which were between 0.1 and 1% of levels observed concurrently in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ethanol-inducible cytochrome P-450: assessment of substrates' specific chemical probes in rat liver microsomes.

The capacity of liver microsomes to oxidize various substrates known to be specific of alcohol-inducible cytochrome P-450 was studied in rats treated with different xenobiotics such as 3-methylcholanthrene, phenobarbital, acetone, and ethanol. Analysis of results showed a significantly marked increase following ethanol and acetone treatments of the p-nitrophenol hydroxylation (283 +/- 19% and 304 +/- 21%), N-nitrosodimethylamine (NDMA) demethylation (280 +/- 105% and 228 +/- 95%), benzene hydroxylation (258 +/- 60% and 236 +/- 61%), butanol oxidation (173 +/- 34% and 154 +/- 32%), aniline hydroxylation (147 +/- 22% and 95 +/- 8%), and ether de-ethylation (95 +/- 17% and 83 +/- 17%) and a not significant increase of N-nitrosodiethylamine (NDEA) de-ethylation (34 +/- 11% and 9 +/- 8%) in rat microsomes, respectively, versus control animals (mean +/- SD, values expressed as nmol/min/nmole P-450). All of these activities significantly decreased after 3-MC treatment, except for the p-nitrophenol hydroxylation. PB treatment markedly enhanced NDEA de-ethylation, p-nitrophenol, and benzene hydroxylations (106 +/- 38%, 109 +/- 14%, and 153 +/- 62%, respectively) versus controls. These results suggest that NDMA and especially 1-butanol are the most specific and useful probes of alcohol-inducible cytochrome P-450 in crude liver microsomes.

Acetone↗

[Computed tomography of soft tissue tumors of the hand and the forearm].

Computed tomography was carried out in 32 patients with clinically equivocal soft-tissue lesions of the hand (24 times) and forearm (8 times). The CT scans were performed with the patients in standard positions; thin slices and zoom technique were used. All soft-tissue tumors were correctly diagnosed with regard to localization, size and infiltration of the surrounding tissue. The histological diagnosis was correct in tendon-sheath proliferations, deposits caused by metabolic disorders, epithelial and ganglion cysts, hemangiomas, lipomas and in one schwannoma. A malignancy was suspected and was proven to be correct in two cases. False-positive diagnoses of a malignant soft-tissue tumor were made in one case of an aggressive fibromatosis, in a rapidly progressive, ossifying myositis, and three times in the presence of postoperative scar tissue following the resection of a sarcoma. Finally, a case of proliferative myositis regarded as semimalignant was underrated by CT. The hand surgeon considered CT diagnostics to be very helpful in planning operations in an anatomically complex organ such as the hand.

Adolescent↗

Ethanol-inducible cytochrome P-450 activity and increase in acetaldehyde bound to microsomes after chronic administration of acetaldehyde or ethanol.

Chronic ethanol consumption results in acetaldehyde adduct formation with proteins such as haemoglobin and liver proteins in vivo. Our purpose was to study the binding of acetaldehyde to liver microsomal proteins, a site of ethanol oxidation via cytochrome P-450 (especially P-450 II E1), after chronic administration of ethanol or acetaldehyde for 21 days to rats. The liver microsomal oxidation of 1-butanol by the ethanol-inducible P-450 also was examined. Acetaldehyde bound to liver microsomal proteins was higher in ethanol-fed rats compared with acetaldehyde-treated rats (0.735 vs 0.413 nmol/mg of protein respectively). The biotransformation of n-butanol to butyraldehyde by liver microsomes was increased (by 136%) in ethanol-fed rats vs controls, whereas in acetaldehyde-treated rats this increase was much lower (only 27%). However, in this last group, a significant negative relationship between the quantity of acetaldehyde bound to microsomal proteins and the monooxygenase-catalyzed transformation of butanol by liver microsomes was demonstrated (r = -0.79, P less than 0.01). These results suggest that proteins of liver microsomes are a target for acetaldehyde binding during ethanol oxidation and such adduct formation could impair the oxidative properties of the alcohol-inducible cytochrome P-450.

Acetaldehyde↗

Measurement of lumbar CSF levels of met-enkephalin, encrypted met-enkephalin, and neuropeptide Y in normal patients and in patients with Parkinson's disease before and after autologous transplantation of adrenal medulla into the caudate nucleus.

The levels in lumbar cerebrospinal fluid (CSF) of neuropeptide Y (NPY), methionine enkephalin (Enk), and Enk contained in amino- and carboxy-terminus extended forms (X-Enk) were examined in nine control patients undergoing elective surgical procedures and in eight patients with advanced Parkinson's disease, before and after the autologous transplantation of adrenal medullary fragments into the right caudate nucleus. The levels of CSF Enk and X-Enk before surgery in patients with Parkinson's disease were significantly less than those observed in control patients (Enk, 166 +/- 38 vs 264 +/- 44 pg/ml; X-Enk, 794 +/- 416 vs 1497 +/- 153 pg/ml). NPY levels did not differ (221 +/- 25 vs 193 +/- 23 pg/ml). After surgery, lumbar CSF samples were taken at 6 weeks, 12 weeks, 6 months, and 9 months. Placement of adrenal medullary fragments into the striatum had no effect on the levels of NPY or Enk at any time point. The levels of X-Enk were significantly enhanced only at 12 weeks (1138 +/- 140 pg/ml) but were at presurgical levels again by 6 months. These data suggest that the transplant was not functionally contributing to the CSF levels of these peptides.

Adrenal Medulla↗

Multicentric chondrosarcomas associated with Ollier's disease. Review and case report.

The malignant transformation of enchondromas in patients with Ollier's Disease is a well known occurrence although few studies have prospectively followed patients with this disease and reviewed the frequency of this process. When malignant degeneration occurs, usually only one focus is noted even though others potentially may be involved. This paper represents a case report in which two separate locations of chondrosarcoma were found. Discussion includes chondrosarcomatous transformation of enchondromas, radiographic findings in this transformation, and treatment of multicentric chondrosarcomas in a patient with Ollier's Disease.

Adult↗

[Computerized tomography of the hand: examination technic, normal anatomy, indications].

The results of 480 computed tomograms carried out in the hand are presented. The digital slice imaging technique shows following advantages: a) Imaging of the complex carpus without superimposition giving a better understanding of carpal biomechanics. b) Anatomically exact imaging of the soft tissues determined by density analysis. In the following states relevant information can be obtained by CT of the hand: 1. Posttraumatic states of the carpus such as scaphoid non-union, lunato-malacia in stages I and II, complex fracture dislocations, and carpal instabilities; 2. cystic transformation of the bone; 3. non-idiopathic CTS; 4. clinically unequivocal soft-tissue masses. In our institution conventional tomography has been largely replaced by carpal CT within a progressive diagnostic programme. Today CT is the best method for imaging soft-tissue masses of the hand.

Carpal Bones↗

[Computed tomographic findings in carpal tunnel syndrome].

Morphometric measurements of the carpal bones were carried out in 32 patients with carpal tunnel syndrome (CTS) and in 47 normal persons, using high resolution CT. Measurements of distances and areas were carried out at the entry of each carpal tunnel and at its narrowest point. In idiopathic CTS there were no significant differences in these measurements from normal carpal measurements. The situation was different in ten patients with nonidiopathic CTS; in these CT showed the cause of median compression reliably. Our results suggest that there are no indications for performing CT of the wrist in idiopathic CTS, but that valuable information may be expected from CT in cases of nonidiopathic CTS.

Carpal Bones↗

[Morphometry using computerized tomography of the wrist in idiopathic carpal tunnel syndrome. Comparison of pre- and postoperative findings].

Alteration of carpal morphometry after surgical release of the carpal tunnel was investigated in 22 patients with idiopathic carpal tunnel syndrome, using pre- and postoperative computed tomography. The morphometric evaluation showed an increase in carpal volume which was due to a palmar soft-tissue prolapse in 90% and to an increase of the carpal arch cross sectional area in about 10%. The carpal tunnel release caused a palmar opening of the canal most commonly at the pisiform bone. There was also a variation in form and an increase in volume of Guyon's canal. The results are discussed and related to the postoperative complaints.

Adult↗