The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.     

Plasma insulin levels in coronary artery disease

Seventy two consecutive patients without a history of diabetes and normal fasting plasma glucose were included in this study of insulin levels. Standard oral glucose tolerance test with 75 gm glucose and fasting and two hour insulin levels were estimated in all patients. Coronary artery disease (CAD) was confirmed or excluded by selective coronary arteriography. In 20 patients, CAD was diagnosed by electrocardiographic (ECG) and clinical evidence of earlier myocardial infarction. Mean fasting plasma insulin was 31.40 +/- 22.2 IU/dl in the CAD positive and 32.3 +/- 13.6 IU/dl in the CAD negative group. The mean two hour plasma insulin was 274.6 +/- 301.1 IU/dl in the CAD positive and 104.8 +/- 74.9 IU/dl in the CAD negative group (p < 0.04). Two hour plasma insulin levels were significantly higher in patients with atherosclerotic coronary artery disease. It is concluded that the estimation of a two hour plasma insulin level after 75 gm of glucose load, could help differentiate CAD from normals.     

Tribological behaviour of MoS2/Au coatings

This study aims to enhance the endurance of MoS₂ coating by applying a thin layer of Au (∼ 80 nm) on MoS₂ surface. Experimental results show that the addition of Au film increases the endurance of MoS₂/Au over equivalent coatings without Au. The friction coefficient rapidly decreases to a stable value (μ ∼ 0.045) after about 100 cycles sliding. After more than 15,000 cycles, the friction coefficient gradually increased to a second stable value (μ ∼ 0.15). An average endurance of over 50,000 cycles was measured in this case. The Au or Au-MoS₂ composite layer can effectively prevent oxygen or moisture reaction with MoS₂ and hence significantly increases the wear life.     

Dental enamel hypoplasia in children with combined congenital and hereditary defects in the development of the CNS and the locomotor system (infantile cerebral palsy, spinal cord hernias and myopathies)]

The incidence of hypoplasia in children with congenital and hereditary developmental defects of the central nervous system and the locomotor system is high (44.5 +/- 3.5%), much higher than the incidence of hypoplasia in children without neurological disorders (2.0 +/- 2.0%). This is explained by exposure of the fetus and newborn to numerous intensive factors complicating the biological anamnesis because of profound disturbances of the metabolic processes and largely responsible for the underlying neurological disease and defects of hard dental tissues presenting as hypoplasia of the enamel.