Search PubMedSearch

Biomedical subjects

S J Fleming

Publications and source records attributed to S J Fleming.

At least 19 recordsLinked to original sources

Glomerular abnormalities in children undergoing orthotopic liver transplantation.

A prospective study of renal function was undertaken on an unselected group of 8 children with chronic progressive liver disease on whom a renal biopsy was performed subsequently at the time of orthotopic liver transplantation. Two patients had abnormal urinalyses and 2 elevated urinary albumin/creatinine ratios. The remainder had no clinical evidence of renal dysfunction. All had normal serum creatinine concentrations. Glomerular abnormalities were present in all renal biopsies and were of two types: hepatic glomerulosclerosis (n = 5) and minor glomerular abnormalities (n = 3). IgM immunofluorescence was present in all biopsies and IgA in 6. Elevated serum immunoglobulin levels were observed in all patients, with IgM elevation in 6, IgA in 4 and IgG in 6. C3 and/or C4 were reduced in 5 patients and increased circulating immune complexes containing IgM were noted in 4. The clinical significance of these cirrhosis-associated glomerular abnormalities can only be established by long-term follow-up studies after orthotopic liver transplantation.

Albuminuria

Universal occurrence of glomerular abnormalities in patients receiving liver transplants.

We conducted a prospective study of renal histology and function in 18 consecutive nonalcoholic patients who underwent orthotopic liver transplantation (OLT). Despite well-preserved renal function, all patients had abnormal renal biopsies. Four patterns of glomerular injury were identified: minor glomerular abnormalities (eight patients), hepatic glomerulosclerosis (seven), membranoproliferative glomerulonephritis (one), and IgA nephropathy (one). In one patient there was insufficient tissue to allow classification. There was a trend toward lower plasma bilirubin and higher plasma albumin in patients with minor glomerular abnormalities than in the group of patients with more severe forms of glomerular injury (29 v 82 mumol/L, 35.5 v 30 g/L; P = 0.1, 0.1 greater than P greater than 0.05, respectively). Glomerular changes persisted in the three patients who died within 7 weeks post-OLT. IgM immunofluorescence was present in all biopsies and IgA in 11. IgM-containing circulating immune complexes occurred in five patients, suggesting a pathogenic role for IgM immune complex deposition. The significance of cirrhosis-associated glomerular abnormalities is not yet known. They may contribute to the hepatorenal syndrome and the renal dysfunction that occurs in up to 94% of patients post-OLT.

Adolescent

Effect of dialyzer reprocessing with Renalin on serum beta-2-microglobulin and complement activation in hemodialysis patients.

The peracetic acid-based sterilant Renalin is increasingly being used for reprocessing hemodialyzers. In order to evaluate the effects of reprocessing on beta 2-microglobulin (beta 2M) kinetics and complement activation in chronic hemodialysis patients, we compared 4 dialyzer membranes on 1st, 2nd and 4th use of the membrane. Dialysis with new cuprammonium rayon dialyzers (0.8 m2) for 4 h resulted in a nonsignificant increase in serum beta 2M concentrations of 10.7% (corrected for changes in extracellular volume) and significant generation of the complement component C3a des Arg. On reuse, minimal changes in serum beta 2M levels were noted and complement activation was absent. Dialysis with new cellulose acetate (CA, 1.5 m2), polyacrylonitrile (AN69 HF, 1.6 m2) or polymethylmethacrylate (PMMA, 1.6 m2) membranes resulted in significant decreases in serum beta 2M levels (19.5, 31.7 and 50.8%, respectively). Reprocessing had negligible effects on the removal of beta 2M by CA and AN69, but by the 4th use halved the effectiveness of PMMA. Reprocessing reduced the significant generation of C3a des Arg observed with new CA and PMMA membranes. We conclude that, except for PMMA, Renalin reprocessing has minor effects on the ability of the membranes to remove beta 2M and improves the biocompatibility of all membranes studied.

Acetic Acid

The use of vaccines in renal failure.

Renal insufficiency is characterised by impaired host defences, which are compromised further by each of the 3 modes of renal replacement--haemodialysis, continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. Reduced renal clearance of unknown toxins, possible development of nutritional deficiencies and administration of immunosuppressive medications lead to aberrant immune regulation early in the course of renal failure. This results subsequently in increased frequency and severity of infection. Vaccination plays an important role in attenuating this infection risk, but impaired cell-mediated and humoral immunity contraindicates the use of live vaccines and engenders suboptimal and short-lived antibody responses to inactivated vaccines. Reinforced vaccination schedules, increased vaccine dosage and concomitantly administered adjuvant immunomodulators have variably improved the defective antibody responses to certain vaccines. Immunisation against hepatitis B virus has resulted in a significant decrease in prevalence and incidence of this infection in haemodialysis units. Similarly, the inoculation of influenza vaccine in patients with uraemia and of polyvalent pneumococcal vaccine in special risk circumstances has been recommended because of perceived reductions in morbidity and mortality from infection with these agents. Cytomegalovirus (CMV) vaccine may attenuate CMV disease severity in recipients of renal allografts. Staphylococcus aureus vaccine, on the other hand, is ineffective in preventing peritonitis or exit site infections in patients receiving CAPD. Other killed vaccines have not been comprehensively studied, but generally have the same indications for use as in normal individuals. However, the protection that these vaccines afford may be either inadequate or transient, so that other infection control strategies should be simultaneously implemented.

Bacterial Infections

Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura: outcome with plasma exchange.

A retrospective analysis was made of 14 consecutive adults with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) who were treated with plasma exchange (PE). In six patients the disease was primary, whilst in eight HUS/TTP was considered secondary to an associated condition. Thirteen patients had renal involvement, six had central nervous system symptoms or signs, three had fever, and one had myocardial damage. Twelve patients (86%) recovered. Four of these relapsed, but responded to further treatment. Two patients failed to respond and died. Hematological response occurred rapidly in survivors: thrombocytopenia resolved after a median of four exchanges, and hemolysis after a median of six. Four patients had a complete recovery, seven had residual mild end organ damage, and one had severe renal impairment. PE was an effective treatment for both primary and secondary HUS/TTP. The platelet count proved to be the earliest indicator of clinical outcome. Continuing follow-up of survivors is required because of the risk of relapse and the high incidence of end organ damage.

Adolescent

Poor response to a recombinant hepatitis B vaccine in dialysis patients.

Eighty-three dialysis patients were inoculated with 20 micrograms of the recombinant derived hepatitis B vaccine Engerix-B at o, I and 6 months. Twenty-seven (32.5%) became seropositive for anti-HBs antibody after the third inoculation. Of the 56 non-responders, 48 received a 40 micrograms booster dose of vaccine 6 weeks after completion of the initial course and a further eight seroconverted. Six months after the third inoculation only 18/71 patients retested (25.3%) had demonstrable antibodies. We were unable to identify clinical or laboratory parameters separating responders from non responders to the vaccine. We recommend regular checks of anti-HBs status of vaccinated patients as it cannot be assumed that even initial responders retain their immunity. Those infection control procedures known to have decreased the incidence of hepatitis B infection in dialysis units should not be relaxed.

Adult

Dialyser reprocessing with Renalin.

We evaluated the dialyser reprocessing agent Renalin in a 6-month prospective study of 2,759 dialyses on 59 patients. Dialysers were withdrawn after a maximum of 6 uses, and the average number of uses achieved was 4.5 Dialyser survival varied with the type of dialyser but was unaffected by the dialysate base. In vivo clearances of urea, creatinine and phosphate were not altered by reuse, but there was a small decrease in ultrafiltration characteristics of used dialysers. No clinically significant adverse event was attributed to reuse. Blood pressure was better preserved with used dialysers, and patients experienced significantly fewer intradialytic symptoms. Savings of over +A 25,000 were achieved during the study.

Acetates

Use of aminohydroxypropylidene bisphosphonate (AHPrBP, "APD") for the treatment of hypercalcemia in patients with renal impairment.

Aminohydroxypropylidene bisphosphonate (AHPrBP, "APD") is a relatively new bisphosphonate which has been shown to be effective for control of hypercalcemia due to a variety of causes. Renal impairment has been reported following the use of other bisphosphonates and pre-existing renal impairment has been regarded as a contraindication to the use of AHPrBP. We report the successful use of intravenous AHPrBP to control hypercalcemia in three patients with renal impairment, one of whom was dialysis-dependent. No significant side effects were noted; in particular, there was no further deterioration in renal function. Intravenous AHPrBP may be a safe and effective agent for the control of hypercalcemia in patients with renal impairment.

Acute Kidney Injury

Bone cysts and haemodialysis-related amyloidosis.

Carpal tunnel syndrome and arthropathy are frequent complications of long-term haemodialysis. Both are associated with cystic lesions of bone and are related to synovioarticular deposition of a new type of amyloid derived from circulating beta 2-microglobulin. Retrospective analysis of the radiographic skeletal surveys of all 58 patients on haemodialysis for 6 or more years revealed one or more cystic bone lesions in 36% of patients. Radiographic analysis indicated that a number of these cysts were due to hyperparathyroid bone disease or joint degeneration, but a majority showed features suggesting an arthropathy of another aetiology. We present evidence that the development of these latter cysts in an individual on long-term dialysis is an indicator of the presence of synovioarticular amyloidosis of the beta 2-microglobulin type. The radiographic characteristics and development of these cysts, which we believe are due to bony infiltration from synovioarticular amyloid are described.

Adult

Urokinase: a treatment for relapsing peritonitis due to coagulase-negative staphylococci.

Four consecutive patients with relapsing peritonitis due to coagulase-negative staphylococci have been successfully treated by the addition of urokinase to their treatment regime, having failed to respond to appropriate antibiotic therapy alone. The organisms isolated from each episode of peritonitis in an individual patient were shown to be identical by antibiotic sensitivity, phage typing, slime production and immunoblot analysis. The action of urokinase is unknown but it may act by fibrinolysis, allowing antibiotics access to a source of infection previously protected by fibrin. The technique described is a simple, safe and effective treatment of relapsing peritonitis due to coagulase-negative staphylococci, and its use can markedly reduce the morbidity associated with this infection.

Bacterial Typing Techniques

Anti-glomerular basement membrane antibody-mediated nephritis complicating transplantation in a patient with Alport's syndrome.

Loss of an allograft caused by anti-GBM antibody-mediated nephritis is a rare complication of renal transplantation in Alport's syndrome. We describe a patient in whom this occurred. He belongs to the subgroup of patients with hereditary nephritis and deafness with an abnormal Goodpasture antigen, and he developed a high level of circulating anti-GBM antibodies within 20 days of transplantation of a kidney with a presumably normal Goodpasture antigen. The antibody titer fell, only to rise again when he developed evidence of acute infection with CMV. Coincident with this second rise in antibody titer he developed an anti-GBM antibody-mediated crescentic nephritis with resultant loss of graft function and transplant nephrectomy. This case provides support for the hypothesis that the abnormality in the basement membrane in some patients with Alport's syndrome involves the Goodpasture antigen, and raises the possibility that viral infection may have triggered autoantibody production.

Adult

Blood volume change during isolated ultrafiltration and combined ultrafiltration-dialysis.

Despite extensive study of the difference in the cardiovascular response to ultrafiltration in isolation and during haemodialysis, there is still disagreement in the literature as to whether or not there is a difference in the efficiency of plasma refilling between the two procedures. We believe that this results both from the use of inadequate techniques to measure change in blood volume and shortcomings in experimental design. We have employed novel methods in ten patients to study plasma refilling during isolated ultrafiltration and dialytic ultrafiltration. Measurement of blood pressure and heart rate confirmed the inferior cardiovascular tolerance to haemodialysis observed by others. However, no difference in the rate of plasma refilling could be demonstrated. Our observations suggest that the superior tolerance to isolated ultrafiltration is not explained by differences in vascular refilling.

Adult

Dialysis-induced change in erythrocyte volume: effect on change in blood volume calculated from packed cell volume.

Blood volume (BV) change during hemodialysis is often monitored by packed cell volume (PCV). This assumes erythrocyte volume is constant. We tested this by dialyzing 5 patients for 2 hours against high (154 mmol/l), normal (140 mmol/l) and low (126 mmol/l) dialysate sodium concentrations. Erythrocyte water content, calculated from measured blood and plasma water contents, decreased with high and increased with low dialysate sodium concentrations. Erythrocyte volume, calculated from mean corpuscular hemoglobin concentration (MCHC) decreased 3.8% with high concentration dialysate and increased 2.5% when dialysate concentration was low. These changes correlated significantly (r = 0.80, p less than 0.01) with alterations in plasma sodium. Mean corpuscular volume (MCV), measured with a Coulter-S Plus Counter did not alter because of a methodological artefact. BV change can be calculated from PCV when plasma concentrations of osmotically active substances are changed only if allowance is made for altered erythrocyte volume.

Adult