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Biomedical subjects

J B Dossetor

Publications and source records attributed to J B Dossetor.

At least 19 recordsLinked to original sources

Ethics in organ donation: contrasts in two cultures.

1. For cadaveric organs in the West, there are many avenues that should be pursued in order to increase the supply. Most of the measures under "giving" in Table 2 are ethical, though we do not accept the implication that those who enroll, in advance, as future organ donors should thereby obtain priority for their own possible future transplant organ needs. 2. "Legislated taking" could be ethically justified if shown to be acceptable to most persons in a society or culture, with provision for opting out for those with minority opinions and beliefs. Such evidence should be sought, and acted upon if found to be present. It certainly warrants a strong public education thrust. 3. Possibilities should be explored for nonmonetary rewarding of families of the decreased, in ways that would not foreclose on families giving authorization for purely altruistic reasons. Direct money payments, "buying," will never outweigh the ethical arguments against the practice, in our opinion. There are other societal avenues by which to pursue the perfectly acceptable goals of indirect altruism. 4. For kidney donations from unrelated living donors in India, a case is made for considering rewarded gifting as being ethically acceptable if it is defined in the way that it is carefully defined for this article, provided it meets the criteria for indirect altruism of a panel of social peers, and also is linked to measures of mandated philanthropy (decided also by a panel of social peers), for the reasons given. This is a balance of societal burden (in allowing rewarded gifting) by the ensured benefit to the seller (to prevent his victimization) plus a required benefit to society by seller's philanthropy. The setting of these balances should be decided by a panel of social peers. Such acceptance would not necessarily pass muster for other cultures than the one for which it is designed. 5. All forms of commerce, included that described in the preceding paragraph, become ethically unacceptable if the regulations governing them cannot realistically be enforced. This is a crucial point, a requirement for ethical cogency.

Cadaver

Kidney stones and lithotripters: critical analysis of the introduction of extracorporeal shock wave lithotripsy into Canada.

It is possible for a nonpharmaceutical medical innovation to enter the mainstream of the health care system without its efficacy and effectiveness having first been established by means of a randomized controlled trial (RCT). The result of this omission may be the discreditation and abandonment of the technology or procedure but not before precious resources that could have been better used elsewhere in the health care system are absorbed. A possible example of such a misallocation of resources is the introduction into Canada of extracorporeal shock wave lithotripsy (ESWL) for the treatment of urolithiasis. We review the development and diffusion of ESWL and recommend ways in which the deficiencies in regulating the introduction of new medical technologies can be corrected.

Canada

Immunoglobulin allotypes in several North American Eskimo populations.

Genetic data consisting of immunoglobulin testing (GM and KM) from 631 Eskimos from 5 populations are reported. These populations are Savoonga, Gambell (St. Lawrence Island), Wales, King Island, and Mckenzie Delta, Baffin Island. The GM and KM haplotypes are analyzed and compared to those occurring in Greenland, Canadian, Alaskan, and Siberian Eskimos and to other Siberian indigenous populations. These analyses suggest that during the peopling of the New World, four separate migrant groups crossed Beringia at various times.

Alaska

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