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Biomedical subjects

G R Catto

Publications and source records attributed to G R Catto.

At least 109 records · Page 6Linked to original sources

Acute renal failure: the tip of the iceberg?

This study reports the experience, during a six-year period, of the Aberdeen Renal Unit in the treatment of patients with acute renal failure. The combination of a relatively stable population base and a single regional dialysis centre has allowed the incidence of acute renal failure to be assessed. Approximately 30 patients per million population were dialysed annually for acute renal failure; 69 per cent of these patients (20.5 per million population per year) were dialysed for acute reversible intrinsic renal failure (ARIRF) and mortality in this group was 44 per cent. Patients with more severe disease at the time of presentation to the renal unit, as defined by a clinical severity score, had significantly reduced survival rates. However, it was not possible to predict the outcome in individual cases; ten of 24 patients with clinical severity scores which indicated a poor prognosis survived the period of oliguria and were discharged from hospital. The fact that other renal units dialyse fewer patients per million population per year for ARIRF probably reflects a reluctance to refer patients whose general condition appears poor. As the overall mortality rate reported in this study does not differ significantly from rates reported previously from centres treating a smaller proportion of patients, such decisions may not be correct. It is well known that facilities in Britain for treating patients with end-stage renal disease are inadequate; it now appears likely that some patients who might benefit from acute dialysis are being denied treatment for a potentially reversible disease process.

Acute Kidney Injury↗

Functional characteristics of the glomerular filter in the IgA-nephropathy.

The purpose of the present study was to compare the functional characteristics of the glomerular filter in patients having a well defined glomerulonephritis, the IgA nephropathy, with those of normal age-matched controls. A bolus intravenous injection of inulin (60 mg/kg), para-amino hippuric acid (36 mg/kg) and Rheomacrodex (130 mg/kg) was administered to each subject and followed by the timed collection of venous blood and urine samples. Compared to the controls, the nine patients with IgA nephropathy had no significant differences in renal plasma flow or glomerular filtration rate. The control group showed filtration of the neutral graded dextrans which diminished in a linear fashion with increasing molecular size. In contrast, the IgA patients showed two-phased glomerular sieving with a reduction in the filtration of dextrans sized 40 A or less and an increased filtration of those larger than 50 A. These changes in dextran filtration indicate the appearance of a population of larger than normal pores in the glomerular filter in the IgA nephropathy, although concomitant alterations in the electrostatic properties of the filter mechanism cannot be excluded.

Adolescent↗

Cyclosporine-induced fetotoxicity in the rat.

Female Lewis rats mated with DA male rats were given 25 or 10 mg/kg/day cyclosporine (CsA) from the time of mating to 20 days postcoitus when autopsies were performed. At the higher dose, characteristic drug-induced pathological changes in the mother were accompanied by a striking fetotoxic effect, resulting in a high incidence of fetal mortality or in runting. In addition, fetal kidneys that could be examined showed evidence of CsA-induced proximal tubular cell damage. These abnormalities were not found at the lower dosage of CsA. The fetotoxicity observed at 25 mg/kg did not appear to be dependent on major histocompatibility differences between parental strains, since it was also observed, at the same dosage, in syngeneically mated female Lewis rats.

Animals↗

The value of Tc-DTPA transit times and NMR T1 measurements in monitoring the progress of renal transplants.

The value of 99Tcm-DPTA transit times and NMR T1 measurements in monitoring the progress of renal transplants has been investigated. Renal transit times were calculated from 182 renograms performed on 29 patients and from 22 of these patients 67 proton spin-lattice relaxation time (T1) measurements were obtained using the Aberdeen Mk 2 NMR Imager. The clinical status of each patient at the time of investigation was defined in retrospect. The principal value of the mean transit time (MTT) was in differentiating between acute rejection and other causes of raised plasma creatinine. During a rejection episode the MTT is raised out of the normal range of 227 +/- 26 s but with chronic rejection or other causes of raised plasma creatinine the MTT remains within normal limits. NMR T1 values appeared to be of little diagnostic value as the normal range was found to be very wide ranging from 340 to 640 ms.

Creatinine↗

Suppression of secondary hyperparathyroidism in uraemia: acute and chronic studies.

A study was conducted evaluating the response of serum parathyroid hormone to acute hypercalcaemia and long term administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients receiving maintenance haemodialysis. During infusion of elemental calcium 4 mg/kg/h over four hours in 12 patients not receiving vitamin D the concentration of serum amino terminal parathyroid hormone fell by 31-96% (mean 74.8 (SD 17.6)%) while that of carboxy terminal parathyroid hormone changed little. There was a strong inverse correlation between baseline serum calcium concentration and percentage fall in amino terminal parathyroid hormone during infusion (r = 0.88; p less than 0.001). In seven patients who received prolonged treatment with 1,25(OH)2D3 after calcium infusion there was a positive correlation between maximum percentage fall in amino terminal parathyroid hormone during infusion and the percentage fall in amino terminal parathyroid hormone after 1,25(OH)2D3 treatment (r = 0.79; p less than 0.05). The responsiveness of the parathyroid glands to changes in calcium in acute studies may be used to predict the efficacy of long term treatment with 1,25(OH)2D3. Patients in whom calcium infusion does not suppress parathyroid hormone may have true parathyroid autonomy and require early parathyroidectomy.

Adult↗

The effect of the dosage of steroids on the incidence of cytomegalovirus infections in renal transplant recipients.

In a retrospective survey of 92 cadaver renal transplant recipients, cytomegalovirus (CMV) infections were detected in 23 of 34 (68 per cent) patients treated with high doses of steroids but in only 27 of 58 (47 per cent) patients given low doses. Pretransplant blood transfusions were associated with both an improvement in one-year allograft survival-rates (P less than 0.05) and an increase in the incidence of CMV infections. When standardised for any transfusion effect, the incidence of CMV infections was significantly higher in those patients given high doses of steroids (P less than 0.05). In the same group of patients, moreover, CMV infections were associated with a statistically significant increase in the renal allograft survival-rate (P = 0.03).

Adult↗

Noncytotoxic antibodies to paternal antigens in maternal sera and placental eluates.

Noncytotoxic antibodies were detected in sera from 6 of 7 primigravid women during the first trimester of pregnancy. Such antibodies directed to antigens expressed on paternal B lymphocytes were detectable within the first 4-5 weeks of gestation. Antibody activity toward paternal B lymphocytes was also detected in 6 of 10 placental eluates, and in 3 of 10 predelivery and 2 of 10 postdelivery maternal serum samples. When B lymphocytes from umbilical cord blood were used as target cells, antibodies were detected in 5 of 7 placental eluates, and in 3 of 7 predelivery and 2 of 7 postdelivery serum samples. These antibodies also reacted with selected members of a normal B lymphocyte panel. The concept of an immunological enhancing mechanism in normal pregnancy is supported by these data.

B-Lymphocytes↗

Non-cytotoxic alloantibodies defined by the EA rosette inhibition assay.

Sera from both transfused individuals and pregnant women mediated inhibition of Fc-rosette formation. Both normal blood B lymphocytes and chronic lymphocytic leukemia cells were used as targets. Inhibition was not related to the presence or absence of lymphocytotoxic antibodies. When tested against a panel of B lymphocytes these sera displayed selective reactivity in keeping with the recognition of allospecific determinants. No association between the target antigen(s) and classically defined MHC-coded structures was evident. Heteroantibodies to both class I and class II MHC structures as well as beta 2-microglobulin also mediated FcR blockade. However, unlike the alloantisera tested, these antibodies displayed no restriction in their reactivity toward individual target cells.

Antibodies, Heterophile↗

Early diagnosis of rejection. Correlation of enzymuria and histological findings after renal transplantation in the rat.

One hundred renal transplants were performed between different rat strain combinations. Posttransplant renal function was monitored using serum creatinine levels, creatinine clearance rates, and N-acetyl-beta-D-glucosaminidase (NAG) enzymuria. These biochemical measurements were compared with the morphological appearances of the transplanted kidney. Rises in NAG enzymuria proved to be useful diagnostic indicators of graft rejection with a false positive rate of only 6%. In 78% of the rejection episodes, the urinary NAG level rose 2 days before any elevation in serum creatinine concentration. There was a close correlation among increasing NAG enzymuria, decreasing renal function, and the structural events of rejection--indicating that the routine measurement of tubular enzymuria would be of value in the prediction and diagnosis of renal allograft rejection.

Acetylglucosaminidase↗

The value of autologous indium (111In)-labelled platelets in the diagnosis of renal transplant rejection.

Serial pelvic imaging after injection of autologous platelets labelled with 111In was used to study 22 consecutive patients following cadaver renal transplantation. Increases in isotope uptake by the allografts were observed during episodes of acute rejection (12/22) but not during acute tubular necrosis (4/22). The technique was not influenced by oliguria or hemodialysis therapy. Extra-renal accumulations of labelled platelets were noted in perinephric hematomata and deep vein thromboses.

Acute Kidney Injury↗

The fetus as an allograft: evidence for protective antibodies to HLA-linked paternal antigens.

Non-cytotoxic antibodies to paternal B lymphocytes were detected in sera from 11 of 11 multiparous women and from 11 of 16 normal primigravidae during the first trimester of pregnancy. These antibodies were not, however, detected in sera from 9 of 10 women of comparable gestation at the time of spontaneous abortion. By means of a rosette inhibition assay, the difference in antibody activity between the primigravidae (mean 37.9 +/- 19%, median 36.5%) and the women subject to spontaneous abortion (mean 7.3 +/- 11.6%, median 0%) was statistically significant. This antibody activity was not directed to the known HLA specificities (HLA--A, B, C, or DR), but linkage to the HLA gene complex was suggested by family studies. These results provide evidence for an HLA-linked antigen system not defined by conventional tissue-typing techniques. Fetomaternal disparity at this antigenic site may be important for successful pregnancy.

Abortion, Habitual↗

Diagnostic value of urinary N-acetyl-beta-D-glucosaminidase, its isoenzymes and the fractional excretion of sodium following renal transplantation.

Daily total urine N-acetyl-beta-D-glucosaminidase activity, isoenzyme profile and fractional excretion of sodium were measured in 13 consecutive renal transplant patients. Rejection episodes were clinically diagnosed in 12 patients, 11 of whom (92%) showed an increased enzymuria either before or during the onset of clinical signs. The ratio of the two major isoenzymes (A/B) fell during 10 episodes (83%) and in six of these (50%) increased levels of the minor isoenzyme forms were observed. Increased fractional excretion of sodium was associated with nine (75%) of the episodes. Increased fractional excretion of sodium with a raised total enzymuria accompanied by a reduced A/B ratio and an increased proportion of the minor isoenzyme forms occurred in eight (67%) of the rejection episodes. The use of these measurements in the diagnosis of episodes of acute rejection in renal transplantation is discussed.

Acetylglucosaminidase↗

Identification of subpopulations of T lymphocytes and Ia positive B lymphocytes using a rosette assay based upon the biotin-avidin interaction.

Bovine erythrocytes were coated with avidin using a chromic chloride coupling technique and used successfully in an indirect rosette assay to identify and quantitate: (a) T-lymphocyte helper and suppressor subpopulations, and (b) Ia positive B-lymphocyte populations. Using mouse monoclonal antibodies to the T-lymphocyte markers OKT3, OKT4, and OKT8 it was shown that the proportion of OKT4 and OKT8 positive cells were respectively 60.9 and 39.2% of the total OKT-3 positive T lymphocytes. In a similar way, using a monoclonal anti-human Ia antibody, the percentage Ia positive cells in B-lymphocyte enriched preparations was shown to vary between 18 and 55% for normal peripheral blood and 31 and 58% for chronic lymphocytic leukaemia derived peripheral blood.

Animals↗

Long-term renal allograft survival in rats preimmunized with donor strain RT1.B antigens.

Rat renal allograft survival was enhanced by active immunization with donor strain RT1.B (Ia) antigens. Lewis (LEW) rats (16) were immunized with Brown Norway (BN) lymphocyte extracts containing RT1.B, but not RT1.A antigens, prior to receiving (LEW X BN)F1 renal allografts. Group 1 (8 rats) was immunized with lymphocyte membrane fragments group 2(8 rats) was primed with lymphocyte supernatant extract. Longterm survivors (greater than 60 days; 12 animals) had a mean blood urea nitrogen of 75 +/- 31 mg% and serum creatinine of 2.0 +/- 0.8 mg% at one month. Death occurred in 90% of control allograft recipients within 10 days. Anti-BN RT1.B but not RT1.A antibodies were detected in sera from actively enhanced rats following immunization and at day 7 posttransplantation. We conclude that preimmunization with cell extracts containing donor RT1.B antigens has a protective effect on the allograft, and that the phenomenon of active immunologic enhancement can be produced without immunization to RT1.A antigens.

Animals↗

Pretransplant antibodies and renal allograft survival.

Fc receptor blocking antibodies directed against autologous lymphocytes were present in pretransplant sera from only one of a group of 24 cadaver donor renal transplant recipients. Such antibodies were present in recipient sera against B lymphocytes from the donor in 11/24, against normal B lymphocytes in 12/24 and against leukaemic B lymphocytes in 15/24 cases. There was a significant correlation between EA inhibiting antibodies directed against donor (p less than 0.01), normal (p less than 0.05) and leukaemic B lymphocytes (p less than 0.001) and improved one year allograft survival. No autolymphocytotoxic antibodies were detected. Fc receptor blocking antibodies detected by the Erythrocyte Antibody Inhibition assay may thus have a beneficial effect on graft outcome but do not appear to be autoantibodies.

Antilymphocyte Serum↗

B lymphocyte antibodies associated with successful renal transplantation and successful pregnancy.

This study shows that non-cytotoxic Fc receptor blocking antibodies occurred more frequently in pre-transplant sera when the recipient had been transfused over five units of blood. Moreover 7/12 previously untransfused patients developed Fc receptor blocking antibodies during an elective blood transfusion regime. Erythrocyte antibody-rosette-inhibiting antibodies were also found at significantly higher values in the sera of women during the first trimester of a normal first pregnancy than in women studied at the time of spontaneous abortion. Family studies showed that this activity was linked to the HLA gene complex. These results indicate that EA inhibiting antibodies directed against MHC linked antigens are associated with specific abrogation of the immune response.

Abortion, Habitual↗