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Biomedical subjects

E Sim

Publications and source records attributed to E Sim.

166 records · Page 10Linked to original sources

Acetylation of arylamines by the placenta.

The N-acetylation of arylamines and hydrazines used as drugs may alter their pharmacological or toxicological activity. Arylamine N-acetyltransferase (NATs) are involved in drug metabolism, as they catalyse the N-acetylation of arylamine and mono-substituted hydrazine substrates. Placental metabolism regulates the nature of the chemicals which reach the developing fetus. The study of drug metabolism during pregnancy is important in determining the effect on the fetus of drugs administered to the mother and the maternal drug dose required, important if the treatment is to be effective. There are two forms of NAT in humans, NAT1 and NAT2, which are encoded at multi-allelic loci. There is inter-individual variation in both NAT1 and NAT2 activity, which has implications in drug dosage. Using a combination of enzyme activity measurements and Western blotting, this study has characterised the arylamine N-acetylation capabilities of placenta and cord blood. NAT1 activity in placenta and cord blood demonstrated inter-individual variation and the variation was in the range expected for adult NAT1 activity. The genotypes of both NAT1* and NAT2* were determined using DNA prepared using placental blood clots (maternal DNA) and cord blood (fetal DNA). The results indicate that placental NAT activity is an important factor when considering N-acetylation during pregnancy.

Acetylation↗

Doppler-echocardiographic assessment of Carbomedics prosthetic values in the mitral position.

We prospectively studied 37 consecutive patients implanted with the Carbomedics prosthetic heart value in the mitral position (without clinical evidence of prosthetic valve dysfunction) with two-dimensional and Doppler echocardiography. The peak mitral prosthetic gradient ranged from 4.60 to 14.63 (mean 8.97 +/- 2.29) mm Hg; mean mitral prosthetic gradient ranged from 1.67 to 6.18 (mean 3.24 +/- 0.95) mm Hg; pressure half-time derived mitral valve area ranged from 1.67 to 5.30 (mean 2.70 +/- 0.80) cm2. These values compare favorably with that of another bileaflet valve (i.e., the St. Jude Medical valve). There was a wide overlap in peak and mean transmitral gradients, even with the valves of the same size, with a significant but weak inverse relationship between peak mitral gradients and valve size (p = 0.03, r = -0.36). The performance index showed a smaller range of values, again with a significant but weak inverse relationship with valve size (p = 0.001, r = -0.54). The inverse relationship between valve size and peak mitral gradient and performance index should be borne in mind when analyzing Doppler hemodynamic data.

Echocardiography↗

[Unicameral cyst of the calcaneus: surgical indications, biomechanical calculations and results of follow-up studies].

Between April 1986 and August 1988, 7 patients (6 men, 1 woman) with unicameral calcaneal cysts were seen at the Trauma Hospital in Meidling. In one case both calcanei were affected. In all cases the findings were accidental, as a result of minor injuries. No familial preponderance was observed. The mean age of the patients was 26.6 years (19 to 33). In 3 patients, filling of the cyst was indicated due to risks from sport or occupational activities. Four cysts were therefore filled with fibrin-spongiosa (homologous bone chips). The mean follow-up interval was 19 months. No recurrent cyst formation was observed, and the patients had no complaints. Nor were there any complications. The importance of CT for preoperative diagnosis and postoperative verification of the result is indicated. On the basis of a strut framework model, it is proved mathematically that cyst formation is not of major importance for the "vertical load case"; on the other hand, bending moments occurring in "inclined load cases" (pronation, supination, extension, flexion), are substantially reduced if the cancellous bone in the cavity region is taken into account. As a logical consequence, surgery is indicated in individuals as risk due to occupational or sports activities; in cases which are not subject to stress peaks, however, therapy is unnecessary.

Adult↗

Immunotoxic side-effects of drug therapy.

Adverse reactions to drugs in which an immune mechanism is responsible for toxicity have been described as idiosyncratic. Understanding these toxic effects is important to enable the identification of patients at risk. The specific toxic side effects considered are heparin-induced thrombocytopenia, penicillin-induced haemolytic anaemia, hepatitis as a result of halothane and tienilic acid therapy, quinine- and quinidine-dependent thrombocytopenia, methyldopa-induced haemolytic anaemia and immune-complex disease following administration of hydralazine, procainamide and penicillamine. The molecular mechanisms of immunotoxicity are presented where such information is available although more than one effect may contribute to the observed pattern of toxicity. The initial events leading to antibody production in certain individuals in response to drug therapy are not understood and, in many of the examples described, antibody production occurs in some patients who do not subsequently experience clinical problems. Clinically serious adverse effects involving immune reactions are infrequent, and a range of genetic and environmental circumstances need to be present simultaneously in an individual before toxicity develops. The ability to metabolise a particular drug has been shown to be one major predisposing factor in toxicity; the immunocompetence of the patient is likely to be another. Both of these considerations are subject to genetic and environmental controls, including infection and disease.

Drug-Related Side Effects and Adverse Reactions↗