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Biomedical subjects

E Steiner

Publications and source records attributed to E Steiner.

At least 145 records · Page 8Linked to original sources
PubMed1988

Polymorphic debrisoquin hydroxylation in 757 Swedish subjects.

The metabolic ratios (MRs) between debrisoquin and 4-hydroxydebrisoquin in urine after a single oral dose of 10 mg debrisoquin were bimodally distributed in 757 healthy, white Swedish volunteers. Forty-one subjects (5.4%) had an MR greater than 12.6 and were classified as slow debrisoquin hydroxylators. The MR was reproducible in urine stored at +8 degrees C for 1 week and at -20 degrees C over a period of 5 years. Collection intervals of 6 or 12 hours gave the same MR. Intraindividual repeatability of the debrisoquin phenotyping test was established in 37 subjects examined twice at least 2 weeks apart. The calculated frequency of the single allele that is believed to control deficient debrisoquin hydroxylation is similar among white Swedish people, as among other white groups examined so far; however, it is significantly different from the frequency in certain Oriental groups. Detailed comparisons of the prevalence of slow debrisoquin hydroxylation in different ethnic groups are not possible due to shortcomings in current epidemiologic techniques used (small materials, the location of the antimode distinguishing rapid and slow hydroxylators unknown, and family studies missing).

Adolescent↗
PubMed1988

Inhibition of desipramine 2-hydroxylation by quinidine and quinine.

Urinary excretion of desipramine (DMI) and 2-hydroxydesipramine (2-OH-DMI) after single oral doses of 25 mg DMI was investigated in seven rapid and three slow debrisoquin hydroxylators, before and after pretreatment with either quinidine or its diastereoisomer quinine. After treatment with 800 mg quinidine daily for 2 days, excretion of 2-OH-DMI decreased by 96% in rapid hydroxylators and 68% in slow hydroxylators. After treatment with 750 mg quinine/day for 2 days, excretion of 2-OH-DMI in rapid hydroxylators was 54% lower than during the control experiment, whereas in slow hydroxylators no significant changes in the excretion pattern were observed. Unchanged DMI constituted only a minor fraction of recovered drug and no significant changes in its recovery were observed in either phenotypic group after pretreatment with quinidine or quinine. Thus both quinidine and quinine decreased the excretion of 2-OH-DMI. At similar does the effect of quinidine was much stronger than that of quinine, virtually transforming rapid hydroxylators into slow hydroxylators. The mechanism probably involves a stereoselective inhibition of DMI 2-hydroxylation.

Adult↗
PubMed1988

Enantioselectivity of 4-hydroxylation in extensive and poor metabolizers of debrisoquine.

Debrisoquine (DQ) has no chiral centre, but hydroxylation in position 4 leads to formation of an asymmetric carbon centre with two possible enantiomers, their absolute configuration being R(-) and S(+)-4-hydroxydebrisoquine (4-OHDQ). Since the absolute stereochemistry of the 4-hydroxylation of DQ in man is unknown, the enantioselectivity of this process was studied in panels of extensive (EM) and poor metabolizers (PM) of DQ. In EM subjects 4-hydroxylation of DQ leads almost exclusively to the formation of S(+)-4-OHDQ. In contrast, PM subjects were not only characterized by a decreased total 4-OHDQ formation but also a marked loss of enantioselectivity in product formation. Between 5 to 36% of total 4-OHDQ was excreted as R(-)-4-OHDQ.

Debrisoquin↗
PubMed1988

Complicated pancreatic abscesses: problems in interventional management.

Twenty-five patients with grade D or E pancreatitis underwent percutaneous drainage. These patients required multiple computed tomography (CT) examinations, multiple catheter insertions, multiple catheter manipulations, and long-term catheter drainage. Eight of the 25 patients were successfully treated with catheter drainage alone. Sixteen underwent surgical drainage, ten after attempts at percutaneous drainage and six prior to radiologic drainage. Of the ten patients who had initial percutaneous drainage, only four were clinically improved from the drainage procedure alone. Although the fluid component of the abscess was often adequately drained in all ten patients, surgery was required to remove pieces of necrotic debris. Six patients who underwent surgical debridement had residual abscesses in the post-operative period and were all successfully treated with percutaneous drainage. One patient died from unrelated causes. Successful interventional management of patients with pancreatic abscesses requires intensive radiologic intervention and monitoring and may be better served by a combination of radiologic and surgical means.

Abscess↗
PubMed1988

Thoracic empyema: management with image-guided catheter drainage.

Forty-three patients with thoracic empyema were treated by means of image-guided catheter drainage. In 40 patients, image-guided catheter drainage was the primary treatment method; in three it was used after conventional, surgical chest tube placement failed. Drainage was performed with ultrasound guidance in 30 patients (69.8%), computed tomography in eight (18.6%), and fluoroscopy in five (11.6%). A combination of guidance modalities was used in six patients. Image-guided catheter drainage alone was successful in 31 of 43 patients (72.1%). In three patients (7%), empyemas were initially drained, but a thoracotomy was ultimately required because of a persistent pleural peel. In eight patients (18.6%), the procedure failed, predominantly due to tube clogging, persistent pneumothorax, or progressive development of a pleural peel. In one patient, drainage was successful but he died 10 days later of complications of renal failure. No major complications were encountered. Treatment of these patients requires a thorough understanding of the pathogenesis of pleural space infection, principles of empyema drainage, techniques of abscess drainage under image guidance, and the use of a pleural drainage system.

Adult↗
PubMed1988

Severe acute pancreatitis after percutaneous biopsy of the pancreas.

A retrospective review of 184 pancreatic biopsies in 178 patients was performed to assess the prevalence of severe postbiopsy pancreatitis. The size, contour, and pathology of the lesions biopsied; the course of the needle (i.e., through bowel or other viscera); the size of the needle; the number of needle passes made; and the guidance technique used were analyzed. Severe pancreatitis developed in five cases (five patients) 5/184 or 3% of the biopsies), usually within 24-48 hr. Three of the five patients who developed pancreatitis had true-negative biopsies (normal pancreas) proved either at surgery (two) or at clinical follow-up (one). The diagnoses for the two remaining patients were adenocarcinomas. In four of the five patients, the diagnosis of severe pancreatitis was made by inspection at surgery. The fifth case was diagnosed by CT. Three patients who underwent surgery and one patient who had percutaneous drainage recovered from the pancreatitis. The fifth patient died despite surgical intervention. All five patients with pancreatitis had masses 3 cm or smaller as compared with the overall group, in which 71 (39%) of the 184 biopsies performed had masses smaller than 3 cm. Overall, 18% of the biopsies were true negative, compared with the 60% true-negative rate in the pancreatitis group. The bowel was transgressed in 21% of all 178 patients, including three of the five pancreatitis patients. We conclude that although the risk of pancreatitis is exceedingly small in percutaneous needle biopsies, it may occur, and at a higher rate than previously reported.

Acute Disease↗
PubMed1988

[Viability of pancreatic transplants].

28 consecutive organ donors were divided in 5 groups according to age (6 to 40, 40 to 65) shock and history of medication requiring hypertension. Electronmicroscopy, histology and immunohistochemistry of the exocrine and endocrine pancreatic tissue, of the ductal and vascular system revealed no abnormalities accept for donors with known hypertension. On the basis of these findings in the future we will remove pancreas from donors up to the age of 65 and from those having been in shock in order to meet the increasing demand for pancreas transplants.

Adolescent↗
PubMed1987

[Gallstone ileus].

From 1965 to 1985 gallstone ileus was diagnosed and treated in 19 patients. The mean preoperative period of symptoms was five days; the correct diagnosis was made in only half the cases. Enterolithotomy alone has proven to be, in comparison with other methods, a reliable procedure with the fewest postoperative complications. Treatment of bilioenteric fistula was limited to symptomatic cases. Improvement of the results can be expected once the interval from first symptoms to operation is reduced.

Aged↗
PubMed1987

The effect of propranolol on exercise induced tachycardia is determined by plasma concentration and the density of adrenergic receptors on leukocytes.

The chronotropic response to a single oral dose of propranolol in 23 healthy subjects has been related to the plasma propranolol concentration and the density of beta-adrenoceptors on peripheral polymorphonuclear leucocytes. The percentage reduction in exercise-induced tachycardia was significantly correlated with the log plasma propranolol concentration within subjects but not between subjects. Taking the concentration of the active metabolite 4-hydroxypropranolol into account did not improve the interindividual correlation. The reduction in exercise-induced tachycardia was significantly correlated with the maximum binding density of (125I)-hydroxybenzylpindolol on polymorphonuclear leucocyte membrane fragments measured before medication. A response index (% reduction in exercise-induced tachycardia/plasma propranolol concentration) was correlated with the maximum binding density of (125I)-hydroxybenzylpindolol (pre-drug) at 2 h (rs = 0.72), 4 h (rs = 0.84) and 6 h (rs = 0.73) after dosing. The data suggest that interindividual variation in the response to propranolol after a single oral dose is determined by interindividual differences both in plasma propranolol and adrenoceptor density.

Adult↗
PubMed1987

Structure-activity relationship in PAF-acether. 3. Hydrophobic contribution to agonistic activity.

The synthesis of some selected PAF-acether homologues with an alkoxy-chain length from C1 to C20 in position 1 is described. All agonist activities are closely correlated among themselves and with the calculated fatty-chain hydrophobicity. After a discussion on recent published results and comparison with our data, we conclude that the ether oxide function is absolutely essential at the glycerol 1-position for potent agonist activity and that potency correlates well with hydrophobicity parameters. We indicate the importance of steric and configurational constraints.

Animals↗
PubMed1987

Differences in the inhibitory effect of cimetidine on desipramine metabolism between rapid and slow debrisoquin hydroxylators.

The disposition of a 25 mg single oral dose of desipramine was investigated in five rapid and four slow hydroxylators of debrisoquin before and during oral administration of 1200 mg cimetidine daily. AUC and elimination half-life of desipramine increased during cimetidine administration in rapid but not in slow hydroxylators. This was the result of a decrease in overall clearance. The urinary recovery of 2-hydroxydesipramine was significantly decreased in rapid hydroxylators during cimetidine administration. We conclude that cimetidine inhibits the metabolism of desipramine in rapid but not in slow hydroxylators.

Adult↗
PubMed1987

The debrisoquin hydroxylation phenotype does not predict the metabolism of phenytoin.

Phenytoin plasma elimination kinetics and accrual of phenytoin metabolites in urine were studied in seven rapid and five slow hydroxylators of debrisoquin. There was no interphenotypic difference in phenytoin clearance, plasma half-life, volume of distribution, maximum rate of metabolism (Vmax), or Michaelis-Menton constant (Km). The total recovery of metabolites as percentage of given dose and the metabolite profiles in urine were similar for the two debrisoquin hydroxylator phenotypes. Similarly, no differences were observed between the groups with respect to stereoselective production of either dihydrodiol or para-phenolic metabolites of phenytoin. The debrisoquin hydroxylation phenotype was also investigated in 74 epileptic patients treated with phenytoin. Vmax and Km were graphically estimated from plasma concentrations at varying phenytoin dosage regimens in 36 of the patients. There was no correlation between the debrisoquin hydroxylation index and Vmax or Km. We conclude that the debrisoquin hydroxylation phenotype has no predictive value in guiding phenytoin dosage.

Adult↗