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Biomedical subjects

J D Briggs

Publications and source records attributed to J D Briggs.

At least 55 records · Page 3Linked to original sources

Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy.

We have investigated the influence of the functional insertion (I) and deletion (D) polymorphism in intron 16 of the gene for angiotensin-converting enzyme (ACE) in a retrospective study of 100 patients with IgA nephropathy. There was no difference in genotype frequency compared with normal subjects. However, patients homozygous for the D allele tended to present at an earlier age (medians: DD, 33; ID, 34; II, 42 years) and to require renal replacement therapy at a younger age (medians 37, 42, and 48 years, respectively). The rate of progression was significantly worse in patients homozygous for the D allele. The DD genotype is associated with increased severity of disease in patients with IgA nephropathy.

Adult↗

Colour Doppler ultrasound in renal transplant artery stenosis: which Doppler index?

A prospective study comparing colour Doppler ultrasound (US) with the 'gold standard' of intra-arterial digital subtraction angiography in the evaluation of renal transplant artery stenosis was performed. Both the intrarenal vessels and the transplant renal artery were examined by Doppler US. Diagnostic arteriography was performed only if, on Doppler, the peak systolic velocity in the transplant renal artery exceeded 1.5 ms-1. Of 109 patients, the transplant artery could not be visualized using colour Doppler US in three, and these were omitted from statistical analysis. Of the remaining 106 patients, 31 had a peak systolic velocity greater than 1.5 ms-1 in the transplant renal artery and were referred for DSA. Of the multiple renal Doppler indices recorded, the peak systolic velocity in the transplant artery was the best discriminating measurement for the detection of renal artery stenosis. A peak systolic velocity of > or = 2.5 ms-1 in the transplant renal artery had a sensitivity of 100% and a specificity of 95% for the detection of renal artery stenosis ( > 50% diameter reduction). Although a significant difference in Pulsatility Index, Resistive Index, Acceleration Index and Acceleration Time was recorded from the intrarenal vessels in the angiographically normal and stenosed groups with Doppler, these measurements were less useful as discriminating diagnostic tests. In conclusion, the peak systolic velocity in the transplant renal artery is the most sensitive Doppler criterion for renal artery stenosis and is sensitive and specific enough to be used as a screening test. The intrarenal acceleration time and index should not be used in isolation.

Angiography, Digital Subtraction↗

Survey of patient selection for cadaveric renal transplantation in the United Kingdom.

The limited supply of cadaveric kidneys results in failure to offer transplantation to all dialysis patients who might benefit. To survey current UK attitudes to selection for renal transplantation and to assess the influence on these attitudes of the shortage of cadaveric donor kidneys, a questionnaire including 20 case histories was circulated to 190 nephrologists and transplant surgeons involved in renal transplantation in the UK. The response rate was 79%. The acceptance rate of individual patients for renal transplantation varied from 19 to 100% of respondents. Almost all patients were significantly (P < 0.05) more likely to be selected for transplantation if an adequate supply of kidneys were available. A correlation was noted between the responses from nephrologists working in Transplant Units and the percentages of their dialysis patients on transplant waiting lists (P < 0.01). This survey strongly suggests that more UK dialysis patients would be offered renal transplantation if the supply of cadaveric kidneys were adequate, and so the current national waiting list, although lengthy, understates the potential demand. Finally, this survey shows the wide variation that exists among both nephrologists and transplant surgeons in their attitude to patient selection for transplantation.

Adult↗

Kidney transplantation decreases the tissue level of advanced glycosylation end-products.

We have studied the effect of chronic renal failure (CRF) and kidney transplantation on advanced glycosylation end-products (AGE) measured as collagen-linked fluorescence (CLF) in the skin and peritoneum of non-diabetic patients. Of 34 patients with CRF, 18 were studied before the commencement of peritoneal dialysis (CRF group), and 16 were studied 5-31 weeks after kidney transplantation (transplant group). The control group consisted of 24 patients with normal renal function. Skin CLF in the CRF group (20.9 +/- 2.02 U/mg) was higher than in the control (8.52 +/- 1.08 U/mg, P = 0.0001) and transplant groups (10.7 +/- 2.43 U/mg, P = 0.003). Peritoneal CLF in the CRF group (30.5 +/- 5.64 U/mg) was higher than in the control group (16.1 +/- 2.25 U/mg, P = 0.031) but was not different from the transplant group (19.4 +/- 3.66 U/mg, P = 0.11). Peritoneal CLF of control and transplant groups were not different (P = 0.45). The results of this study suggest that restoration of renal function affects tissue AGE levels.

Adult↗

Hepatitis C virus infection detected by antibody tests and the polymerase chain reaction as a cause of liver dysfunction in renal transplant recipients.

Hepatitis C infection (HCV) is more prevalent in patients who have received kidney transplants than in the general population but the morbidity and mortality associated with infection in this group is unclear. Sera taken from 36 renal transplant recipients with chronic liver dysfunction and from 42 with normal liver function were tested for HCV infection by second generation ELISA (Abbott Laboratories) and second generation recombinant immunoblot assay (Chiron Corporation) (RIBA-2). Evidence of HCV replication was sought by reverse transcription polymerase chain reaction (RT PCR) using primers from the 5' nontranslated region (5'NTR). Infection was detected in 20/36 (54%) and in 2/42 (4.8%) controls (P < 0.01). Twelve liver dysfunction patients were positive by all three tests, six were positive by ELISA and RT PCR but had indeterminate RIBA-2, one was positive by ELISA and RIBA but negative by RT PCR, and one was positive only by RT PCR. Of two infected control patients, one was positive by all three tests and one who was later found to have been in the early stage of infection was positive only by RT PCR. Follow-up of infected patients showed persistence of viraemia in 14/15 (93%). Evidence of infection with different types of HCV was shown by the lack of amplification by RT PCR by primers with mismatching bases with HCV types 2 and 3. It is concluded that in our renal transplant patients, chronic HCV infection is usually associated with liver dysfunction and persistent infection is common.

Adult↗

Long-term outcome of the use of OKT3 to treat steroid-resistant acute renal allograft rejection.

OKT3 was used to treat steroid-resistant acute renal allograft rejection in 30 of 496 adult patients transplanted over a 6-year period. Rejection was reversed (defined as a fall in serum creatinine by 50% or more within 30 days of treatment with OKT3) in 40% of cases. Successful reversal was significantly more likely when rejection occurred shortly after transplantation (t ratio -2.53; P = 0.019). The long-term outcome was disappointing; the actuarial graft survival at 1 year from the start of treatment with OKT3 was 42%, and no grafts have thus far survived longer than 3 years. Graft survival was shorter in older patients (coefficient/standard error 2.226; P < 0.05), and no other predictor of long-term outcome was identified. Patient survival at 3 years was 88%. Serious infection occurred in 33% of patients, with two deaths. Our experience suggests that treatment with OKT3 is unlikely to reverse acute renal allograft rejection in more than half of patients where rejection is resistant to steroids. Although long-term graft survival occurred in a few cases, the overall long-term outcome was disappointing, particularly in older patients. Finally, our analysis indicates the difficulty of predicting which patients will derive long-term benefit when OKT3 is used to treat steroid-resistant rejection.

Acute Disease↗

Evaluation of a Bayesian approach to the pharmacokinetic interpretation of cyclosporin concentrations in renal allograft recipients.

The utility of a Bayesian parameter estimation program in the interpretation of cyclosporin concentrations was investigated in a group of 32 patients following renal transplantation. The program was evaluated by comparing concentrations predicted from individual estimates of pharmacokinetic parameters with measured concentrations. A one-compartment model incorporating an exponential, time-related change in clearance was used for data collected in the first 4 weeks after transplantation, and predictions of concentrations measured during weeks 5-14 were made using three schemes: a changing clearance model using all data from week 1 onward; a changing clearance model using data from week 4 onward; and a nonchanging clearance model using data from week 4 onward. Results demonstrated that predictions made by the Bayesian program were unreliable during the first 4 weeks of therapy, but that there was a progressive improvement as time after transplantation increased. The changing clearance model was superior to the constant clearance model and its performance was not compromised by including data from the first 4 weeks of therapy. Although the Bayesian approach may help with the interpretation of blood cyclosporin concentrations during maintenance therapy, the large variability in the pharmacokinetics of orally administered cyclosporin limits the usefulness of the approach in the early weeks following transplantation.

Adult↗

Relations of selected variables and perception of success in volleyball.

This study examined the relations of selected variables and the perceived success of 39 college-age subjects participating in a beginning volleyball class. Measures of motor trials, successful motor trials, preclass mood, perceived challenge, perceived behavior of the teacher, and perceived success were taken on 11 separate days during an 8-week class. The mean response for the 11 days was used for statistical analysis. Pearson's product-moment correlations indicated all predictor variables were significantly related to perceived success. A stepwise multiple regression analysis showed that preclass mood was the best predictor of perceived success, with perceived challenge, teacher's perceived behavior, and successful motor trials also entering the regression equation.

Adolescent↗

Hepatitis C virus infection in renal dialysis patients in Glasgow.

A survey of all 483 adult dialysis patients in the three renal units in Glasgow using second-generation ELISA was carried out to determine hepatitis C virus (HCV) seroprevalence in the summer of 1991 before the introduction of blood donor screening for antibody to HCV in the UK. Supplementary testing of ELISA positive sera was by second-generation immunoblot assay (RIBA-2, Chiron). Retrospective case note analysis and testing of stored sera were performed to assess liver function and the risk factors for acquisition of the virus. Nineteen of the 483 patients (3.9%) were seropositive. Sixteen patients had been transfused and 12 had previous transplants. Seropositivity was associated with current haemodialysis (P < 0.01) rather than continuous ambulatory peritoneal dialysis (CAPD). Of those on haemodialysis, the time since first dialysis was longer for seropositives (13.6 years) than for seronegatives (6.3 years) (P < 0.01) but this did not apply to those on CAPD. Twelve of 19 (63.2%) seropositives had persistent elevations of alanine transferase compared to seven of 38 (18%) seronegative controls (P < 0.01). This large group of dialysis patients is at special risk of HCV infection but the seroprevalence is less than that reported from outside the UK despite the use of more sensitive techniques. The risk is associated with haemodialysis and is probably largely due to blood transfusion. The introduction of screening of donated blood for HCV antibody should reduce the incidence of new infection in dialysis patients.

Adolescent↗

Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human kidney allografts.

Expression of the cellular adhesion molecules ICAM-1, VCAM-1, E-selectin and PECAM in human kidney allografts was assessed by immunoperoxidase labelling of cryostat sections. Biopsies from 10 kidneys immediately prior to transplantation and 58 biopsies from 51 kidney transplants with graft dysfunction were studied. Allograft dysfunction was due to acute tubular necrosis (n = 5), acute rejection (n = 30), cyclosporin A (CyA) nephrotoxicity (n = 6), acute pyelonephritis (n = 3), recurrent glomerulonephritis (n = 4) and chronic rejection (n = 10). There was variability in the distribution of ICAM-1, VCAM-1 and E-selectin expression in pretransplant kidneys but the principal observation was a marked increase in the expression of ICAM-1 and VCAM-1 by the renal vasculature and the proximal tubules during acute rejection. By contrast, grafts with dysfunction not attributed to rejection showed a pattern of ICAM-1 and VCAM-1 expression similar to that observed prior to transplantation. E-selectin was expressed only weakly by occasional intertubular capillaries during acute rejection but the three grafts with pyelonephritis displayed strong expression of E-selectin on intertubular capillaries. There was no change in the pattern of PECAM expression following transplantation. The induction of ICAM-1 and VCAM-1 during rejection may contribute to the recruitment of mononuclear cells and render endothelial and tubular renal cells more susceptible to cell-mediated injury.

Adolescent↗