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Biomedical subjects

J B Dossetor

Publications and source records attributed to J B Dossetor.

At least 37 records · Page 2Linked to original sources

An alternative approach for statistical analysis of kidney transplant data: multivariate analysis of single-center experience.

To avoid the center effect and the possible hidden interactions of multicenter studies, the validity of the Cox Proportional Hazards Model for the analysis of a single-center kidney transplant program was tested, considering 287 renal transplants performed in a 10-year period. The inclusion of type of donor and main immunosuppressive drug as covariates in the model did not violate the proportionality assumption of the Cox model. According to this method, the following covariates were significant in predicting graft survival: cyclosporine, type of donor, good human leukocyte antigen (HLA)-A and HLA-B match (DR data were not considered), highest percentage of reactive antibodies against panel cells, and nephroangiosclerosis as a primary renal disease. Cyclosporine did not significantly improve graft survival in living related donor transplants. Pretransplant blood transfusions, cold ischemia time, and donor ABO blood group were initially significant but dropped out in the step-down procedure. Recipient's age at transplant, cyclosporine, HLA-A and HLA-B match, and nephroangiosclerosis were significant in predicting patient survival. It was concluded that using long-term data of cadaveric and living related renal transplants either on azathioprine or cyclosporine is a valid way to perform multivariate analysis of single-center transplant programs that do not have large samples.

Adult↗

An extracorporeal model of biofilm-adherent bacterial microcolony colonization for the study of peritonitis in continuous ambulatory peritoneal dialysis.

We have developed an extracorporeal system for investigating in vitro the biofilm-adherent bacterial microcolonies (BABM) that grow on Tenckhoff catheters (TC), to study peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A modified Robbins' device, attached to sampling plugs with TC discs and connected to the dialysate via a peristaltic pump, is run for 24 h; scrapings from pairs of TC discs are processed for assessment of viable BABM, one of each pair for culture by routine microbiology techniques and the other for examination by scanning and transmission electron microscopy (EM). No colonization was noted with fresh dialysis solutions and spent dialysates from patients without clinical peritonits; but, when bacterial suspensions were added to aliquots of the same dialysates, BABM were noted on both culture and EM. In a study of 4 patients on CAPD treatment, who had clinically evident peritonitis, routine cultures of spent dialysate were positive in only 2, but BABM were found in cultures and EM preparations of disc scrapings in all 4 cases. We conclude from these preliminary findings that this extracorporeal system is reliable, and well suited for studying the role of BABM in CAPD-associated peritonitis in vitro.

Bacterial Adhesion↗

Combined evaluation of circulating immune complexes and antibodies to Pseudomonas aeruginosa as an immunologic profile in relation to pulmonary function in cystic fibrosis.

We developed a solid-phase radioimmunoassay with a reference standard pseudomonas antigen and used this with 125I-labeled anti-human immunoglobulin to evaluate specific antibodies to Pseudomonas aeruginosa, qualitatively and quantitatively, in sera from children with cystic fibrosis (CF) whose lungs were colonized by this bacterium. The results of this IgG assay correlated with the number of precipitin antibodies to the standard reference antigen determined by cross-immunoelectrophoresis in the same sera. Forced expiratory volume (FEV1; percentage predicted), determined as an indicator of lung injury in CF, was evaluated as an immunologic response to pseudomonas, against a profile derived from combined serial data on both the circulating immune complexes (CIC) and the Ps. aeruginosa antibodies (N = 25 CF patients; 108 sera). This revealed that in CF patients who had no specific IgG antibodies to Ps. aeruginosa and no IgG-CIC had the best pulmonary function (FEV1 = 115 +/- 14.52%) and those with high levels of antibodies to this organism and high IgG-CIC levels had the poorest lung function (FEV1 = 69.75 +/- 10.99%) (P less than 0.05). We believe that this indicates an immunologic basis for lung injury in cystic fibrosis.

Antibodies, Bacterial↗

A randomized study of cyclosporine with and without prednisone in renal allograft recipients. Canadian Transplant Group.

Sixty-nine patients receiving Cs after cadaveric or LRD renal transplants were randomly allocated to receive prednisone or no prednisone beginning on the day of transplant. There were 36 in the prednisone group and 33 in the group assigned to no prednisone. Of these latter, only seven (21%) never received prednisone and an additional four had one short course for rejection episodes (11%). Of the remaining 22 who were placed on continuous steroids, only 12 met rejection criteria and either some or all of the remainder probably had Cs nephrotoxicity. The patient and graft survival were better but not statistically so in the no-prednisone group (97% v 89%) and (88% v 78%), and the number of infections was only half that of the prednisone-treated group (22% v 42%). A policy of withholding steroids except for rejection episodes does not prejudice graft or patient survival in Cs-treated patients.

Cyclosporins↗

Prognostic implications of circulating immune complexes and Pseudomonas aeruginosa-specific antibodies in cystic fibrosis.

We re-examined the role of circulating immune complexes (CIC) in cystic fibrosis, by their serial measurement in 16 patients who had advanced lung disease and persistent specific antibodies to Pseudomonas aeruginosa in their serum. CIC were detected by 125I C1q-BA (IgG + IgM-IC) and Raji RIA (IgG-IC), and IgA-IC by a modification of the Raji RIA method. Serum precipitins to Ps. aeruginosa were detected by crossed-immunoelectrophoresis (XIE) and antibodies to alkaline protease (AP), elastase (EL) and exotoxin-A (EA) of Ps. aeruginosa were detected by ELISA technique. CIC were positive in greater than 50% of the samples in 8 patients (group A) and in less than 25% in the other 8 (group B); follow-up averaged 22 mo in group A and 26 mo in group B. The numbers of precipitins to Pseudomonas were equally high, and levels of antibodies to AP, EL, and EA of Ps. aeruginosa were similarly positive, in the 2 groups. In group A the CIC were mostly IgG-IC by Raji RIA (76%) and IgA-IC, whereas in group B C1q-binding IC (79%) and IgA-IC were more prevalent than IgG-IC by Raji RIA. Four group A children died during follow-up, together with one group B child in whom the CIC level had suddenly risen precipitously. We postulate that a high level of CIC in association with persistent specific-antibody response to Ps. aeruginosa heralds a poor prognosis in cystic fibrosis.

Adolescent↗

Human T cell subset ratio quantitation by 51Cr release: assessment of a new technique.

A method for T cell subset ratio quantitation is described. This technique makes use of monoclonal antibodies 66.1 (OKT4 equivalent) and 51.1 (OKT8 equivalent) in complement-dependent cytotoxicity. The percentages of 51Cr release with these 2 reagents from peripheral blood lymphocyte targets were used to calculate the ratio. It is simple, inexpensive, and can be used for large numbers of samples, but is less accurate when compared with the microscopic technique in immunofluorescence. It may serve as a screening test in certain clinical situations where there is need to determine the T4/T8 ratio.

Antibodies, Monoclonal↗

Elevated natural killer cytotoxicity in HLA-B8 and HLA-DR3-positive individuals.

Increased natural killer cytotoxicity in persons positive for HLA-B8 and HLA-DR3 has been found. It is suggested that linkage disequilibrium between the genes coding for HLA-B8 and HLA-DR3 may have evolved as a result of strengthened immunological surveillance in individuals bearing them, as decrease in the frequency of both these antigens has recently been reported in patients with tumours.

Adult↗

Segregation of HLA A,B haplotypes and the distribution of antigen mismatches between mother and offspring in Hutterite families.

Segregation of HLA haplotypes and offspring genotype distributions were analyzed in families from an inbred Caucasoid population, the Dariusleut Hutterite Brethren. Both parents and from one to 12 offspring were typed for HLA-A and -B antigens in 108 families. Segregation of paternal haplotypes was analyzed conditional on sibship size in 95 sibships (a total of 547 offspring), and segregation of maternal haplotypes, in 90 sibships (a total of 515 offspring). The distribution of the number of different genotypes among the offspring was analyzed conditional on sibship size in 90 families (515 offspring) where four equiprobable genotypes were expected. The distribution of the number of antigenic differences or mismatches for broad specificities between mother and offspring was analyzed in pooled family data consisting of a total of 377 offspring comprising 68 families. Compared with the multinomial distribution of segregation classes of haplotypes, there was no significant departure (probability .05 or less) from the expected segregation ratio for either paternal or maternal haplotypes. Compared with the multinomial distribution of the number of genotypes among the offspring, only two of the 11 sibship sizes had configurations that exceeded the 5% level of significance. Given the number of statistical tests performed, it is likely that these results could be explained by chance variation. Finally, there was no relative deficiency of offspring who were less mismatched with their mother for HLA-A and -B broad specificities. Therefore, if HLA-A,B region variation does have a major effect on the differential survival of fetuses in some families, it is an uncommon factor among fertile couples from this inbred population.

Alberta↗

Cyclosporine-associated lymphoproliferation, despite controlled cyclosporine blood concentrations, in a renal allograft recipient.

In a patient receiving sulfinpyrazone (Anturan, Geigy) an unusually high dose of cyclosporine (Cys) was required to maintain serum values in the range of 50-200 ng/ml. After eight months of 1300-1500 mg/day, the patient complained of increasing malaise and symptoms of cyclosporine side-effects. This clinical state was accompanied by splenomegaly and two monoclonal peaks in the gamma region on serum electrophoresis. Concomitantly, rising cytomegalovirus IgM titres, following by rising IgG titres, indicated a primary cytomegalovirus infection. This ominous biclonal proliferation markedly diminished during the subsequent six months, during which time the cyclosporine dose was minimised. He returned to good health, splenomegaly and monoclonal gamma globulin virtually disappearing. He remains well at 16 months post-transplantation.

Cyclosporins↗

Detection of IgG in supernatants of pokeweed mitogen-stimulated human lymphocyte cultures by one step solid-phase radioimmunoassay (SPRIA).

A one step solid phase radioimmunoassay is used as a simple and reproducible method of detection and quantitation of IgG produced by human PBL after stimulation with PWM. Modifications of culture conditions are necessary to make culture supernatants suitable for this assay. Pulsing with PWM must be performed in serum-supplemented culture medium for 4-5 days. After thorough washing, medium is then replaced with serum-free medium. Under these conditions, synthesis and secretion of IgG continues for at least 9 days. The amount of IgG produced by 10(6) normal adult PBL as detected in this system is 0.77 +/- 0.47 micrograms. No close correlation between cell proliferation and IgG synthesis was observed.

Culture Media↗

Anti-IgM antibodies may regulate the humoral response to paternal HLA antigens in pregnant women.

Anti-IgM antibodies were detected in sera of pregnant women but not in non-pregnant women and men. Anti-IgM activity was associated negatively with presence of anti-HLA antibodies. This finding suggests possible immunoregulatory influence of anti-IgM on humoral response against major histocompatibility antigens in pregnancy. The possibility of a similar mechanism being responsible for enhancement of kidney graft survival due to blood transfusions is discussed.

Antibodies, Anti-Idiotypic↗