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Biomedical subjects

R W Johnson

Publications and source records attributed to R W Johnson.

At least 145 records · Page 8Linked to original sources

Comparison of serologic and biochemical definitions of HLA class I polymorphisms in cadaver renal transplantation.

The role of biochemical variants in matching renal donors with recipients was investigated in a population of 26 donor recipient pairs from the period 1979-85. Serologic typing was compared with a biochemical analysis of HLA-A and -B antigens in a group in which there had been no mismatches for HLA-A and -B antigens by serology. HLA-A and -B serology was updated using stored material for 92.2% of the renal recipients and donors (n = 51), and HLA-A, -B, and -DR serology was updated for 84.3%. No inconsistencies were found with the HLA-A and -B antigens assigned at the time of transplant. HLA-A and -B antigens of 70% of the renal recipients and donors were analyzed by immunoprecipitation from lymphocytes and serum and analyzed after isoelectric focusing by autoradiography and Western blotting. No biochemical differences between recipient and donor were found for any one pair when HLA-A and -B antigens were serologically the same. This biochemical analysis was useful in providing results where there was doubt over the presence or absence of an antigen serologically. In a well-matched situation, HLA-A and -B serologic types were concordant with results obtained biochemically. However, in a poorly matched situation this could be different.

Antibodies, Monoclonal↗

Donor seropositivity and prednisolone therapy as risk factors for cytomegalovirus infection and disease in cyclosporin-treated renal allograft recipients.

We attempted to assess the importance of blood transfusion, donor seropositivity, and prednisolone therapy as risk factors for cytomegalovirus infection in cyclosporin-treated renal allograft recipients. Primary infection was diagnosed in 27 of 86 patients (31 per cent) and recurrent infection in 27 of 79 patients (34 per cent). Receipt of banked blood from unselected donors after transplantation did not increase the incidence of primary infection in the few transfused patients. Kidney donor seropositivity and maintenance prednisolone in addition to cyclosporin were associated with increases in the incidence of primary or recurrent infection, respectively. Cytomegalovirus infection was clinically mild. Presumed bacterial pneumonias occurred in three patients with recurrent cytomegalovirus infection. The absence of severe cytomegalovirus disease probably reflected the minimal use of prednisolone. Matching of seronegative donors with seronegative recipients seemed unjustifiable in cyclosporin-treated renal transplant patients.

Adult↗

A continuous cardiac output computer based on thermodilution principles.

A totally self-contained instrument for the measurement of cardiac output is described. The microcomputer controlled instrument is based upon the principles of thermodilution and is capable of making cardiac output determinations on a minute by minute basis. A bolus of heat is delivered to the blood via a resistive heating element wound on the surface of a conventional thermodilution catheter, and the resulting transient pulmonary artery blood temperature increases is monitored with the thermistor located near the tip of the catheter. The performance of the instrument was tested in a mock circulatory loop and in dogs for periods of up to 13 hours. The accuracy and reproducibility of flow determinations made with the system compare favorably with those made with a conventional cardiac output monitor. This study demonstrates the feasibility of a stand-alone cardiac output computer that can provide virtually continuous measurements of blood flow without the intervention of a technician.

Animals↗

Central venous blood temperature fluctuations and thermodilution signal processing in dogs.

Pulmonary artery blood temperature fluctuations are a principle source of variability of thermodilution cardiac output measurements. Two signal processing strategies were investigated to decrease this variability; a subtractive noise cancellation algorithm, developed from a heat balance model of heat transport through the right heart, and a band pass integration technique. Blood temperature fluctuations were recorded from the inferior and superior vena cavae and the pulmonary artery in four dogs. The recorded temperature signals were processed off line to investigate the performance of the signal processing strategies. The findings indicate that the accuracy of the heat transport model, while dependent on the accuracy of the sensing of caval blood temperature, is sufficient for cancellation of a significant fraction of the pulmonary artery thermal noise power if the amplitude of the fluctuations is large. The use of the subtractive cancellation algorithm improved the standard deviation of thermodilution curve area determinations by a factor of five, relative to area estimates made without noise cancellation. Band pass integration produced a more modest improvement in area estimate reproducibility. These results demonstrate that it is possible to reduce, but not eliminate, the variability of thermodilution cardiac output measurements with the described processing strategies.

Animals↗

Enzyme-linked immunosorbent assay for the diagnosis of clinical and subclinical melioidosis.

An enzyme-linked immunosorbent assay (ELISA) for the detection of specific IgG and IgM antibody to Pseudomonas pseudomallei was developed. The IgG-ELISA was compared with the indirect fluorescence assay for IgG antibody (IgG-IFA) and the indirect hemagglutination (IHA) test in studies with serum specimens from persons from endemic areas for melioidosis and from persons from nonendemic areas of Australia. The sensitivity and specificity of the IgG-ELISA were 90% and 99%, respectively, comparable to those obtained with the IgG-IFA. The IgG-ELISA was more sensitive than the IHA test (74%) and was more suitable than the IgG-IFA as a serologic screening test for melioidosis. The IgM-ELISA was compared with the IgM-IFA as a marker of disease stage in patients with melioidosis. There was good diagnostic agreement between the tests; 92% of patients with active disease gave IgM-ELISA titers greater than or equal to 1:5,120 and 93% of patients with subclinical melioidosis had IgM-ELISA titers less than or equal to 1:1,280. Of the overlap group of patients with a borderline IgM-ELISA titer of 1:2,560, approximately 33% were clinical cases. An uncommon disease stage consisting of a self-limited, short-term, flu-like, pyrexial illness accompanied by elevated serum IgM-ELISA titers (greater than or equal to 1:5,120) was seen in a small number of patients residing in endemic Australia.

Adolescent↗

Evidence that matching for HLA antigens significantly increases transplant survival in 1001 renal transplants performed in the northwest region of England.

In the 20-year period from March 1968 to March 1988, 860 patients received 1001 renal transplants in the Northwestern Regional Renal Transplant Unit at Manchester Royal Infirmary. Through a continuing policy of avoiding mismatches for HLA antigens and lymphocytotoxic antibody crossmatching, transplant survival rates were found to correlate with the degree of HLA-A and B antigen mismatching from 1968 to 1978 and with HLA-B and DR antigen mismatching from 1979 to 1988. Mismatching for HLA-B and DR antigens was also found to correlate with transplant survival in highly sensitized patients and in patients transplanted since 1981, the "cyclosporine era." Recipients who were HLA-DR1 positive were found to have the highest graft survival compared to recipients negative for this antigen. In contrast, HLA-DR3 positive recipients had the poorest outcome. Transplants from HLA-DRw6 positive donors showed higher transplant survival rates than donor kidneys positive for any other HLA-DR antigen. A correlation of transplant survival with HLA-B and DR mismatching was seen whether kidneys were collected within our region or received through the UK Transplant Service. We conclude that avoidance of mismatching for HLA-B and DR antigens confers high transplant survival rates (91.1% at 5 years for 0 HLA-B and DR mismatches), and in order to achieve this rate for most recipients exchange of donor kidneys between transplant centers will be essential.

Adolescent↗

Pharmacokinetics of cyclosporin: influence of rate-duration profile of an intravenous infusion in renal transplant patients.

1. The pharmacokinetics of cyclosporin were studied in six renal transplant patients, following intravenous administration of 5 mg kg-1 infused over 3, 6 and 24 h. 2. Plasma, separated at 37 degrees C, was analysed for cyclosporin by h.p.l.c. 3. The data were described by a biexponential disposition model. 4. None of the disposition parameters (clearance, initial volume of distribution, half-lives) changed with the duration of infusion.

Adult↗

Cyclosporin-erythromycin interaction in renal transplant patients.

1. The interaction between cyclosporin (CyA) and erythromycin was studied in renal transplant patients following oral and intravenous administration of CyA. 2. Blood and plasma CyA concentrations and blood concentrations of metabolite 17 were measured by h.p.l.c. 3. Erythromycin produced almost a two-fold increase in bioavailability, from 36% to 60%; with a small (13%) decrease in clearance of CyA. 4. The metabolite 17 data further support the postulate that erythromycin increases the absorption of CyA rather than inhibits its metabolism, as generally believed.

Administration, Oral↗

Kidney transplantation in the northwest region of England--experience of 1,132 transplants in 21 years.

1. In more than 1,100 kidney transplants performed at a single center in 21 years a conservative approach to immunosuppressive therapy and HLA antigen matching has ensured high survival rates after both short- and long-term follow-up. 2. Retransplantation has been carried out in 16.6% of patients with transplant survival rates not differing significantly from those in first transplant recipients. 3. Living-related donor transplants accounted for only 7.9% of cases since 1982 and transplant survival was no different from HLA-A,B,DR-identical cadaver donor transplants. 4. Pretransplant blood transfusions were given to over 98% of recipients since 1982 and transplant survival in such CsA-treated patients was 10% higher than in the few nontransfused recipients. 5. By adopting a meticulous policy of pretransplant cytotoxic antibody screening and HLA antibody definition followed by careful pretransplant crossmatching using all available patient sera, accelerated transplant rejection has largely been avoided. 6. Monitoring of posttransplant recipient sera has shown that the appearance of cytotoxic antibodies leads to transplant failure and these antibodies are usually directed against HLA antigens mismatched between donor and recipient. 7. Matching for HLA antigens has a striking positive effect on transplant survival with more than 30% difference between the no mismatch and no match groups. Positive HLA matching effects on transplant survival were found in retransplants, highly sensitized recipients, male and female recipients, all ABO blood groups, and after long-term (20 years) follow-up.

Adolescent↗

No minor issue.

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Cultural Characteristics↗