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Biomedical subjects

E Sim

Publications and source records attributed to E Sim.

At least 55 records · Page 3Linked to original sources
PubMed1989

Size polymorphism of the erythrocyte complement receptor type 1 (CR1) in systemic lupus erythematosus induced by hydralazine.

The human erythrocyte complement receptor type 1 (CR1) is polymorphic with respect to molecular weight. Size variants with molecular weights of 190,000 (type A), 220,000 (type B) and 160,000 (type C) daltons have been detected in normal individuals (22 individuals), patients with hydralazine (Hz) lupus (n = 27), a group of Hz controls (n = 30) and the relatives of both Hz groups (27 and 11 individuals, respectively). The method of detection was SDS-polyacrylamide gel electrophoresis of erythrocyte membranes on low-percentage cross-linked gels followed by Western blotting using polyclonal rabbit anti-CR1 antibodies. In normal individuals, 77% had the A allotype and 26% carried the B allotype; amongst Hz lupus patients 67% carried the A allotype, 31% carried the B allotype, and 3% (1 individual) had the C allotype. Amongst the patients who had been on Hz but did not develop SLE, 83% carried the A allotype and 17% carried the B allotype. The AA phenotype was only found in 44% of Hz SLE patients but in 64% of normals and 70% of the Hz control group. Although not statistically significant, the results indicate a relative underrepresentation of the AA phenotype in patients with Hz-induced SLE. In addition, an equal or greater relative amount of the C allotype was detected in an Hz SLE patient with the AC phenotype. This is in contrast to lower relative amounts of the C allotype found in normal individuals with this phenotype.

Erythrocyte Membrane↗
PubMed1989

Drug-induced immune-complex disease.

A range of drugs including hydralazine, isoniazid, procainamide and penicillamine cause toxic side effects which resemble systemic lupus erythematosus (SLE). Deficiencies of C1, C4 and C2 are associated with idiopathic SLE, and these defects may compromise the ability of the patient to deal with immune complexes. Immune complexes with protein as antigen, such as has been reported to be diagnostic of procainamide-induced SLE, interact more with the C4A isotype of C4 than the C4B isotype. It is shown that hydralazine, isoniazid and penicillamine inhibit the covalent binding of C4 to a complement-activating surface and that the drugs themselves become covalently bound to C4. For each of these drugs, C4A is inhibited more than C4B, and it is suggested that this is an important contributory factor in the development of the toxic side effects to these drugs involving immune-complex deposition. For procainamide, it is shown that the hydroxylamine metabolite rather than the drug itself inhibits the covalent binding reaction of C4. Hydralazine, isoniazid and procainamide are metabolised by the polymorphic N-acetyltransferase, and slow acetylators are at increased risk of drug-induced lupus. For procainamide, oxidation to the hydroxylamine form is an alternative metabolic route of increased importance in slow acetylators, and it is suggested that investigation of C4 type in susceptible patients could provide a means of identifying those at greatest risk of immunotoxicity.

Humans↗
PubMed1989

CR1 polymorphism in hydralazine-induced systemic lupus erythematosus: DNA restriction fragment length polymorphism.

The contribution of genetic factors in the reduction in erythrocyte CR1 levels observed in hydralazine (Hz) induced systemic lupus erythematosus (SLE) was investigated by determining the frequency of a HindIII restriction fragment length polymorphism (RFLP) in the CR1 gene. This RFLP is associated with quantitative erythrocyte CR1 expression. Individuals who have developed SLE as a reaction to Hz therapy, consanguinous relatives of the Hz-SLE patients, controls who had been treated with Hz without any adverse reaction, and the consanguinous relatives of these controls were included in this study. No difference was found in the frequency of occurrence of the alleles associated with CR1 expression between the Hz-SLE patients and the control groups (P greater than 0.2). Individuals from the Hz-SLE group who were homozygous for the 7.4 kb 'high expressor' allele had lower mean levels of erythrocytes CR1 (564 +/- 65) than the corresponding homozygous subgroups within the Hz-SLE relative group (774 +/- 46), the Hz control group (756 +/- 80) and the Hz control relatives group (825 +/- 66). In addition, 50% of the Hz-SLE patients in the 'high expressor' subgroup who had less than 500 CR1 per erythrocyte had elevated levels of circulating immune complexes. This study suggests that individuals who are genetically low expressors of erythrocyte CR1 are not predisposed to developing SLE in response to Hz therapy, and that in a subgroup of genetically 'high expressors', low CR1 levels are associated with elevated levels of circulatory immune complexes.

Alleles↗
PubMed1989

[Osteopoikilosis--fracture healing].

Between 1956 and 1988 five cases of osteopoikilosis have been observed. All cases were found by chance. In two cases there were fractures: one of the femur shaft, which has been stabilized by intramedullary nailing, one of the fifth metacarpal bone which has been treated conservatively. In both cases no delay of bony union could be observed. Osteopoikilosis- as a mesenchymal lesion--seems to have no negative influence on fracture healing.

Bone and Bones↗
PubMed1989

[Dislocations of the carpometacarpal joint of the thumb--results of follow-up].

This report deals with twenty-nine dislocations of the carpometacarpal joint of the thumb--twenty-five closed and four compound dislocations, three of which were part of complex injuries of the hand--treated during the period 1957 to 1983. The closed dislocations comprised eighteen dorsal, three dorsal-ulnar, two dorsal-radial, one palmar, and one palmar-ulnar. The compound dislocations comprised one radial (isolated), one palmar-radial, one dorsal-radial, and one palmar-ulnar; the last three occurring together with complex injuries. Eleven patients were followed up after an average period of about eleven years. Closed dislocations including those with minor tears of ligaments and/or the joint capsule do not require operative treatment. Reduction and immobilization for four weeks in a plaster splint with inclusion of the thumb were sufficient; recurrence of the dislocations did not occur. The compound dislocations required temporary transarticular Kirschner wire fixation as the ligament and the capsule were completely torn.

Adolescent↗
PubMed1989

[Comparison of the value of magnetic resonance tomography and computerized tomography in the follow-up of augmentation-plasties with carbon fiber ligaments of the anterior cruciate ligament].

17 patients--treated with unidirectional carbon-fibre-ligaments augmentation for the anterior cruciate ligament--have been followed-up by MRI and CT. The question has been, whether both methods show comparable results. The interval between operation and follow-up has been 34 months in average (43 to 30). Significance was put on the probants bedding. MR-Imaging in two planes seems to be essential to show the artificial ligament's integrity in its extraarticular "over the top"-position. Satisfying corresponding results could be found in MRI and CT.

Adolescent↗
PubMed1988

Metabolites of procainamide and practolol inhibit complement components C3 and C4.

Drug-induced systemic lupus erythematosus arises from toxic side-effects of administration of hydralazine, isoniazid, procainamide and practolol. Hydralazine and isoniazid are nucleophilic drugs and inhibit the covalent binding reaction of complement components, C3 and C4, an effect likely to lead to deposition of immune complexes (a feature of systemic lupus erythematosus). Procainamide and practolol do not themselves inhibit C3 and C4. A range of metabolites and putative metabolites of procainamide and practolol were synthesized, and tested for their ability to inhibit the covalent binding reactions of C3 and C4. The highly nucleophilic hydroxylamine metabolite of procainamide was strongly inhibitory in both tests, as was a putative hydroxylamine metabolite of practolol. These studies indicate a potential role for the hydroxylamine metabolites in mediating the toxic side-effects of procainamide and practolol, and emphasize the need for adequate measurements of hydroxylamine metabolites in human tissue.

Acecainide↗
PubMed1988

Interaction of nucleophilic compounds with complement component C4.

Drugs which induce systemic lupus erythematosus as a toxic side effect have been shown to inhibit the covalent binding of C4, which is an important event in immune complex clearance in normal individuals. Human C4 is encoded at two polymorphic loci, C4A and C4B within the Major Histocompatibility Complex and patients with idiopathic SLE are more likely to have a non-functional (null) C4A gene. The C4A and C4B gene products differ in reactivity with C4A being more reactive with nitrogen nucleophiles, including hydralazine and isoniazid (drugs which induce SLE), than with oxygen nucleophiles. We have established an assay system which allows the effect of nucleophiles on C4 in animal sera to be investigated. It has been found that in comparing reactivity of guinea-pig C4 with human C4A and human C4B that guinea-pig C4 is like human C4A and shows greater reactivity towards nitrogen nucleophiles than towards oxygen nucleophiles. This suggests that the guinea-pig should be a good animal model for drug-induced SLE.

Animals↗
PubMed1988

The effect of indication on the risk of hypersensitivity reactions associated with tolmetin sodium vs other nonsteroidal antiinflammatory drugs.

A retrospective cohort study using 1980-1984 Medicaid billing data from 3 US states was performed to assess the relative risk of hypersensitivity reactions from different nonsteroidal antiinflammatory drugs (NSAID). Comparing tolmetin sodium to other NSAID, pooling the data across the 3 US states using the Mantel-Haenszel procedure, gave an overall relative risk (95% confidence interval) of 1.1 (0.8-1.4). After adjusting for multiple potential confounding variables using logistic regression, an odds ratio (95% confidence interval) of 0.9 (0.6-1.2) was observed. These data do not confirm previous suggestions that use of tolmetin is associated with a higher risk of hypersensitivity reactions than use of other NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Transcutaneous oxygen monitoring and retinopathy of prematurity.

This study was performed to determine whether the use of continuous tcPO2 monitoring could reduce the incidence of ROP in preterm infants receiving oxygen therapy. Two hundred and ninety-six infants with birth weights less than or equal to 1300 grams were randomly assigned to a continuous monitoring (CM) or a standard care (SC) group. CM infants had tcPO2 monitored continuously as long as they required supplemental oxygen while SC infants had tcPO2 monitored only during the more acute state of their illness. Management of both groups was otherwise identical. One hundred and one of 148 infants in the CM and 113 of 148 patients in the SC groups survived. Mean birth weights and gestational age were similar in both groups. Duration of mechanical ventilation and oxygen therapy was also similar. The overall incidence of ROP was 51% in the CM and 59% in the SC group. As birth weight for infants greater than or equal to 1000 grams increased a higher risk for developing ROP was noted in the SC group. Four infants in the CM and 5 in the SC group developed cicatricial ROP. These results suggest that continuous tcPO2 monitoring may reduce the incidence of ROP in infants with birth weights greater than 1000 grams, but not in the smaller infants in whom this complication occurs more frequently and is more severe.

Birth Weight↗
PubMed1987

Retinopathy of prematurity. A randomized, prospective trial of transcutaneous oxygen monitoring.

To determine whether the use of continuous transcutaneous oxygen monitoring (tcPO2) could reduce the incidence of retinopathy of prematurity (ROP) in pre-term infants receiving oxygen therapy, a randomized, prospective trial of constant monitoring using the transcutaneous oxygen monitor versus intermittent monitoring of oxygen was performed on a population of premature infants at very high risk for the development of ROP. Two hundred ninety-six infants were randomly assigned to either a constantly monitored (CM) or standard care (SC) group. CM infants had tcPO2 monitored continuously as long as they required supplemental oxygen, whereas SC infants had tcPO2 monitored only during the more acute state of their illness. Management of both groups was otherwise identical. One hundred one of 148 infants in the CM group and 113 of 148 in the SC group survived. The overall incidence of ROP was 51% in the CM group and 59% in the SC group (no significant difference). In infants over 1000 g birthweight, as the weight increased there was increasing risk of developing ROP in the SC group. The odds ratio for the ROPsc:ROPcm reached 7.6 in infants between 1200 and 1300 g in infants with Apgar scores greater than or equal to 8 at 5 minutes. The incidence of cicatricial ROP was similar in both groups: four in the CM and five in the SC group.

Blood Gas Monitoring, Transcutaneous↗
PubMed1987

Erythrocyte complement receptor type 1 (CR1) expression and circulating immune complex (CIC) levels in hydralazine-induced SLE.

Family studies were carried out to look at CR1 expression in 24 hydralazine-induced SLE patients (Hz Reactors), who had been off the drug for at least 1 year and were clinically well at the time of the study. Mean expression of CR1 was reduced by 27% in the group of hypertensives who had developed Hz-induced SLE compared with a group of 35 normal individuals. CR1 expression was also slightly reduced in the relatives of the Hz Reactors compared to the normal group. Using a solid-phase Clq binding assay, CIC levels were found to be elevated in the plasma of the Hz reactors and an inverse relationship was found between CR1 levels and CIC levels in this patient group. Both CR1 levels and CIC levels in Hz Reactors and normal individuals were constant over the 36 weeks studied. This study suggests that there is an association between an inability to deal efficiently with CIC and susceptibility to developing Hz-induced SLE.

Antigen-Antibody Complex↗
PubMed1987

Upper gastrointestinal tract bleeding from oral potassium chloride. Comparative risk from microencapsulated vs wax-matrix formulations.

A retrospective cohort study was performed to assess the relative risk of upper gastrointestinal (UGI) tract bleeding from two formulations of potassium chloride. Relevant information was obtained from 1980 through 1984 Medicaid billing data from the states of Michigan, Minnesota, Florida, and Ohio. After patients with a history of UGI tract bleeding prior to their first prescription for either of the two potassium chloride preparations under study were excluded, data were analyzed for 28,790 patients (143,512 patient-months) dispensed a microencapsulated formulation exclusively and 76,118 patients (560,341 patient-months) dispensed a wax-matrix formulation exclusively. The risk of UGI tract bleeding within 30 days after each prescription for the drug of interest was examined. After sampling from the undiseased study subjects and adjusting for multiple potential confounding variables using logistic regression, an odds ratio (95% confidence interval) of 0.67 (0.52 to 0.85) was observed.

Administration, Oral↗
PubMed1987

Influence of transcutaneous oxygen monitoring on the incidence of retinopathy of prematurity.

This study was performed to determine whether the use of continuous transcutaneous oxygen tension (tcPO2) monitoring could reduce the incidence of retinopathy of prematurity in preterm infants receiving oxygen therapy. A total of 296 infants with birth weights less than or equal to 1,300 g were randomly assigned to a continuous monitoring or a standard care group. Infants in the continuous monitoring group had tcPO2 monitored continuously as long as they required supplemental oxygen, and infants in the standard care group had tcPO2 monitored only during the more acute state of their illness. Management of both groups was otherwise identical. Of 148 infants in the continuous monitoring group, 101 survived; of the 148 patients in the standard care group, 113 survived. Mean birth weights and gestational ages were similar for both groups. Duration of mechanical ventilation and oxygen therapy was also similar. The overall incidence of retinopathy of prematurity was 51% in the continuous monitoring group and 59% in the standard care group. As birth weight for infants greater than or equal to 1,000 g increased, a higher risk of retinopathy of prematurity developing was noted in the standard care group. Cicatricial retinopathy of prematurity developed in four infants in the continuous monitoring group and five in the standard care group. These results suggest that continuous tcPO2 monitoring may reduce the incidence of retinopathy of prematurity in infants with birth weights greater than 1,000 g but not in the smaller infants in whom this complication occurs more frequently and is more severe.

Birth Weight↗
PubMed1986

Phenotyping of human complement component C4, a class-III HLA antigen.

The plasma complement protein C4 is encoded at two highly polymorphic loci, A and B, within the class-III region of the major histocompatibility complex. At least 34 different polymorphic variants of human C4 have been identified, including non-expressed or 'null' alleles. The main method of identification of C4 polymorphic allotypes is separation on the basis of charge by agarose-gel electrophoresis of plasma. On staining by immunofixation with anti-C4 antibodies, each C4 type gives three major bands, but, since individuals can have up to five allotypes, the overlapping banding pattern is difficult to interpret. We show that digestion of plasma samples with carboxypeptidase B, which removes C-terminal basic amino acids, before electrophoresis, produces a single, sharp, distinct band for each allotype and allows identification of the biochemical basis of the multiple banding pattern previously observed in C4 phenotype determination.

Carboxypeptidase B↗