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Biomedical subjects

E Sim

Publications and source records attributed to E Sim.

At least 19 recordsLinked to original sources

Arylamine N-acetyltransferase in human red blood cells.

N-Acetyltransferase activities associated with erythrocytes from 20 individuals have been determined with p-aminobenzoic acid as substrate. A three-fold variation in Vmax is found. The N-acetyltransferase genotype of the individuals has been determined and there is no correlation between the extent of acetylation measured in the individuals' erythrocytes and the inheritance of alleles at the polymorphic NAT locus. Folate is confirmed to be an inhibitor of arylamine N-acetyltransferase activity measured in erythrocytes. The content of folate in erythrocytes of individuals also varies. The individual with the maximum folate content has the minimum N-acetyltransferase activity. The monomorphic N-acetyltransferase gene from individuals spanning the range of N-acetyltransferase activity have been amplified, using the polymerase chain reaction. The pattern of restriction enzyme digestion of the monomorphic N-acetyltransferase gene with a series of eight restriction enzymes is the same for individuals spanning the activity range of arylamine N-acetyltransferase in their erythrocytes.

4-Aminobenzoic Acid

The fixateur interne for stabilising fractures of the thoracolumbar and lumbar spine.

Between 1986 and 1988, 27 patients with fractures of the thoracolumbar and lumbar spine were treated by fixateur interne (FI) instrumentation, and 24 were followed up for a mean of 25 months. Complications occurred in 13 cases, mostly due to loosening and corrosion. The results were compared with plate fixation. The radiological parameters and differences between the preoperative and postoperative indices were well within the normal range. The inferiority of FI instrumentation compared to plate fixation during follow up was mainly attributable to the complications. Reduction of the posterior wall fragments by the intact posterior longitudinal ligament was not consistent, so instrumented reduction is usually the method of choice.

Adolescent

Surgical management of right colon diverticulitis.

The infrequent occurrence of right colon diverticulitis in the developed West has led to a controversy in the management of this disease. In Singapore, we continued to avoid colectomy whenever possible because this disease is usually nonprogressive. We reviewed 68 patients treated by conservative surgery to evaluate the effectiveness of this treatment policy. Almost 70 percent of our patients were below 40 years of age, and the clinical presentation was indistinguishable from acute appendicitis. Diverticulectomy was done only for inflamed and perforated diverticula (25 cases), while the nonperforated diverticulum was left alone (40 cases). The inflammation invariably responded to antibiotic therapy. Only three patients had colonic resection since a malignant neoplasm could not be excluded. There were no adverse sequelae over a mean follow-up period of three and one-half years, except for one patient who had recurrent attacks of right colon diverticulitis necessitating colectomy. With this policy of management we encountered no mortality, and morbidity was acceptable.

Adult

Genotyping human polymorphic arylamine N-acetyltransferase: identification of new slow allotypic variants.

Arylamine N-acetyltransferase catalyses the N-acetylation of primary arylamine and hydrazine drugs and chemicals. N-acetylation is subject to a polymorphism and humans can be categorized as either fast or slow acetylators according to their ability to N-acetylate polymorphic substrates in vivo. Previously, slow acetylation has been linked to four distinct polymorphic N-acetyltransferase (pnat) alleles each of which contains one or more point mutations within the coding region of the pnat gene. One new rare slow variant of pnat has been identified by cloning and sequencing the pnat DNA from an individual whose NAT phenotype was determined by in vivo acetylation of the polymorphic substrate sulphamethazine. This allele, designated S1c, differs from the wild type fast allele at nucleotide positions 341 and 803. A second new rare slow allotypic variant, designated S3, has been identified by resistance of the pnat specific DNA to digestion with the restriction enzymes Fok I and Bam HI. A method of genotyping individuals for the arylamine N-acetyltransferase (NAT) polymorphism is presented which correctly predicts the phenotype of greater than 95% (21 of 22) of individuals as measured by the extent of acetylation of sulphamethazine in urine. This refined genotyping method was applied to a clinical population of 48 Caucasians with classical or definite rheumatoid arthritis each receiving daily between 150 and 500 mg of the anti-rheumatic drug, D-penicillamine. There is no difference in the N-acetyltransferase phenotype of the individuals who developed proteinuria and the control group with no adverse effects.

Adult

[Interlocking nailing of the femur--analysis of problems and errors based on 80 fractures].

A series of 79 patients with 80 femoral fractures stabilized by the Grosse-Kempf interlocking femoral nail system (Howmedica) were critically evaluated for the frequency of problems and technical mistakes during surgery. Problems with patient positioning were negligible. In patients with fractures at a suitable site, the Wittmoser table proved useful. Closed reduction should not be attempted at all costs: in borderline cases, open reduction should be given preference to prevent complications. Radiologically relevant problems included: twisted nails, 27.5% of all cases; broken nails, 2.5%; bent nails, 1.2%. Proximal screws were too long in 18.7%, too short in 1.5%, placed too far cranially in 29.6%, shifted (with damage to the thread) in 3.1%. Distal screws were too short in 11.7%, too long in 16.1%, protruding laterally in 2.9%, malpositioned in 1.4%; affected by ectopic calcifications in 4.4%, by cortical fragmentation in 8.8%, and loosing in 10.2%; both screws broke in one case. Technical mistakes during surgery were faulty assessment of the fracture pattern in 7.5%, a wrong impaction site in 23.7%, and bursting of the proximal fragment in 11.2%. Leg shortening was observed in 8% (16 mm, on average) and lengthening in 11.2% (6.2 mm, on average). Rotational malalignment was seen in 23 of 35 patients followed up clinically: inappropriate external rotation (12.5 degrees, on average) in 12 patients and inappropriate internal rotation (10 degrees, on average) in 11. Implant damage was seen in 8.7%. A breakdown of the complications by the operating surgeons involved clearly shows where the problems lies: 80 fractures were treated by 25 surgeons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[The long-term behavior of homologous bone transplants in reconstruction of single chamber calcaneus cysts. Conventional and computerized tomography results].

Treatment of four unicameral calcaneal bone cysts by operative packing with homologous trabecular bone grafts was evaluated by conventional radiography and CT after a mean follow-up time of 51 months (range 48-57 months). Data on graft incorporation and remodelling are presented. In all cases trabecular bone showing an orderly arrangement was found to have developed in the cyst space. Homogeneous areas were present in 2 instances. These coincided with the neutral triangle, i.e. a zone in which stresses are physiologically low. Graft incorporation and remodelling followed Wolff's laws of bone transformation and can be regarded as complete before month 27. The final bone pattern is definitely established before month 50. Conventional radiography is sufficient for routinely evaluating the healing pattern. CT should be reserved for research purposes. Impaction of trabecular bone chips may be dispensable. Tight packing without impaction would at least help to save bone graft material. The use of homologous trabecular bone subjected to special pretreatment was found to be unproblematic. It minimizes surgery-related stresses and reduces the operating time.

Adolescent

[Intravenous peripheral digital subtraction angiography after stabilization of medial femoral neck fractures. Results and value].

In patients with medial femoral neck fractures the condition of the blood vessels is the decisive factor as to whether or not femoral capital necrosis will develop. Therefore, conventional angiography has been used both preoperatively for the diagnostic work-up and for selecting the best mode of management and postoperatively for prognostic purposes. Its routine use has, however, been limited by the long examination time, the complexity of the technique and the potential complications. Peripheral intravenous digital subtraction angiography (DSA) for imaging peripheral vessels is a far less demanding procedure. Its usefulness was studied postoperatively in 7 patients. The vascular information obtained was inferior to that of conventional angiography because of the inherently poorer vessel imaging qualities. Moreover, since its applicability is limited to patients with a completely intact cardiovascular system and normal cardiac output, it is not suitable for most geriatric patients. It is, therefore, concluded that peripheral intravenous DSA cannot (yet) be recommended as a routine procedure. It remains to be seen whether technical improvements in system features will improve the diagnostic performance.

Adult

[Spinal internal fixator--analysis of problems in 28 cases].

Problems encountered in the management of thoracolumbar and lumbar spinal fractures with the "fixateur interne" are reviewed. 28 patients were treated between 1986 and 1988. Retrospective analysis identified the following problems: a. Loosening of nuts at the longitudinal rod and/or clamp ends--b. Major corrosion defects of Schanz screws and clamps--c. Large implant volume--d. Non-availability of intermediate rod lengths. Earlier problems, i.e. the absence of an effective press-fit (transverse stabilizer) between the 2 longitudinal rods and the non-availability of a cutter for trimming the Schanz screws, have meanwhile been resolved. Loosening of the nuts at the clamp end may cause substantial loss of reduction and jeopardize the outcome of treatment. The problem of how to identify loosening, which is usually recognizable within 27 days, is discussed at length. Since loosening occurs irrespective of fracture type and site, instrumentation length, ancillary surgical procedures, type of postoperative care, preoperative neurological status and operating surgeon, it appears to be inherent in the system. Alterations in neighbouring vertebral segments attributable to rebundant rod lengths cannot altogether be excluded. The potential occurrence of corrosion defects should prompt implant removal after radiologically confirmed fracture healing.

Adult

N-acetyltransferase polymorphism. Comparison of phenotype and genotype in humans.

N-Acetyltransferase (NAT) isoenzymes are encoded at two loci. One locus encodes an NAT which is expressed widely in tissues, does not vary amongst human individuals and is termed monomorphic NAT (mNAT). The second locus encodes an NAT which is termed polymorphic NAT (pNAT), has a distinct tissue distribution and is responsible for the difference in ability between individuals in acetylating certain arylamine (e.g. sulphamethazine) and hydrazine (e.g. isoniazid) drugs which are polymorphic substrates. We describe a simple DNA based method for genotyping individuals for pNAT. The 'fast' NAT allele (F1) and the three 'slow' alleles (S1, S2 and S3) can be distinguished by using PCR with oligonucleotide primers specific for pNAT followed by restriction enzyme digestion of the amplified product. Heterozygotes are easily identified. The genotype of individual Caucasians compares well with the extent of acetylation of sulphamethazine. The allele distribution of the Caucasian population described here differs from that reported after Southern blot analysis of a Japanese population (Deguchi et al., J Biol Chem 265: 12757-12760, 1990). The most frequent allele at the polymorphic nat locus in Caucasians, S1, is absent in the Japanese population. This difference between the two populations is likely to be the basis of the known interethnic variation in acetylator phenotype frequencies.

Acetylation

Drug metabolising N-acetyltransferase activity in human cell lines.

Many arylamine and hydrazine drugs and xenobiotics are acetylated by N-acetyltransferase (NAT), a cytosolic enzymic activity which has a wide tissue distribution. Humans can be classified as either fast or slow acetylators on the basis of their ability to metabolise isoniazid or sulphamethazine. These are termed polymorphic substrates. The acetylation of other compounds does not vary amongst individuals, e.g., p-aminobenzoic acid, and are termed monomorphic substrates. NAT from human hepatic and non-hepatic tissues, viz., (i) liver, (ii) the hepatoma cell line HepG2, (iii) tonsil lymphocytes and (iv) the monocytic cell line U937 have been compared with respect to substrate specificity towards polymorphic and monomorphic substrates. The chromatographic and centrifugation behaviour of NAT from these sources has also been investigated. NAT from liver shows 2-fold greater activity towards sulphamethazine than towards p-aminobenzoic acid as substrate. All other cell types tested show at least 70-fold greater activity with p-aminobenzoic as substrate compared to sulphamethazine. NAT from HepG2 cells, U937 cells and tonsil lymphocytes migrates as a single peak during ion-exchange chromatography, whereas the liver NAT activity is separated into two peaks. NAT in HepG2 cells resembles extra-hepatic tissue NAT rather than NAT in liver. HepG2 cells do not therefore represent a good in vitro model for investigation of human metabolism of arylamines or hydrazines. The molecular weight of NAT from U937 cells has been determined by a combination of sucrose density gradient centrifugation and gel filtration to be 31,600 +/- 1200 daltons.

Arylamine N-Acetyltransferase

Intramedullary wiring for tibial shaft fractures in children before epiphyseal closure. Indications and technique--experience of 36 patients.

Between 1958 and 1987 36 children underwent intramedullary wiring for tibial shaft fractures. Of these, 29 presented with combined tibial and fibular fractures, and 7 showed isolated tibial shaft fractures. Fractures were simple in 22 and compound in 14 patients. Mean patient age was 13 years (4-16 years). Only bending fractures with and without splinters were wired. The wiring technique and the protocol for postoperative care are reviewed. Mean immobilization time in long-leg casts was 12 weeks; intramedullary wires were removed after a mean interval of 17.7 weeks. Patients were selected for intramedullary wiring because of compound fractures of variable severity (14 patients), brain injuries with associated fractures (1), relative separation of the fracture ends with the fibula intact (2), severe dislocation or expected instability following closed reduction (9), and secondary dislocation or unsatisfactory alignment on skeletal traction (9). Complications included infections of 2nd degree compound fractures (2 patients), transitory peroneal palsy (2) and delayed union (2). Non-union and damage related to immobilization were not seen. A total of 19 patients were available for follow-up. Mean follow-up time was 9 years. Posttreatment lateral displacement was found to be irreversible except in infants but had no functional relevance. Malalignment showed a tendency towards spontaneous correction, which decreased with increasing age. Correction surgery proved to be unnecessary. Differential longitudinal growth was not consistently evaluable because of the heterogeneity of the material; reported data on this parameter from the literature were equally inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Dorsal technique of vertebral body reconstruction using cortico-cancellous bone chips].

Grafting of cortico-cancellous bone is firmly established in trauma surgery especially as concerns surgical stabilization of the spine. Early references to that procedure can be traced back to Magerl's reports, but it was Daniaux who decisively improved spongiosa reconstruction and published the results. Further modifications were introduced by Thielemann and Holz as well as by Arnold. All techniques applied so far are essentially based on the implantation of cancellous bone. The method presented employs cortico-cancellous grafts.

Bone Transplantation

[Clinical aspects of bedside bars].

The use of a bar at the side of a sick-bed by old confused patients may be the origin of implant failures and dislocations after stabilisation of fractures of the upper third of the femur by various implants or endoprosthesis. An inexpensive possibility of solution is shown.

Aged

The low risk of upper gastrointestinal bleeding in patients dispensed corticosteroids.

PURPOSE: To determine the incidence of upper gastrointestinal bleeding in patients treated with corticosteroids. PATIENTS AND METHODS: The incidence of upper gastrointestinal tract bleeding was assessed in a cohort of 19,880 patients from the Michigan Medicaid billing database with dermatitis and/or asthma treated with corticosteroids during 1980 to 1984. The frequency of upper gastrointestinal bleeding was assessed within 60 days after each corticosteroid prescription. RESULTS: The incidence of upper gastrointestinal bleeding in patients without a past history of upper gastrointestinal bleeding who were exposed to corticosteroids was only 2.8 cases per 10,000 person-months. The rate of upper gastrointestinal bleeding was notably higher in patients receiving anticoagulants and those with a prior history of upper gastrointestinal bleeding (23.0 and 15.9 cases per 10,000 person-months, respectively). CONCLUSION: Because the incidence of upper gastrointestinal bleeding in ambulatory patients treated with corticosteroids is so low, prophylactic therapy should be restricted to high-risk patients, if it is to be used at all.

Adolescent