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Biomedical subjects

N M Thomson

Publications and source records attributed to N M Thomson.

At least 55 records · Page 3Linked to original sources

Intraperitoneal (IP) vancomycin therapy for CAPD peritonitis--a prospective, randomized comparison of intermittent v continuous therapy.

The use of intraperitoneal (IP) vancomycin as initial, single agent therapy for gram positive and "no organism" continuous ambulatory peritoneal dialysis (CAPD) peritonitis is described, comparing continuous and intermittent administration schedules. "Continuous" therapy consisted of an IP 1-g loading dose of vancomycin followed by 30 mg/L dialysate effluent. "Intermittent" therapy consisted of 2 IP doses of 30 mg vancomycin/kg body weight--the initial dose delivered at diagnosis and the second dose 1 week later. All patients presenting with peritonitis (n = 90) were randomized to receive either continuous or intermittent vancomycin therapy. Patients in whom gram negative organisms and fungi were identified by microscopy and culture were transferred to therapy with a more appropriate antibiotic (n = 39). In the remainder (n = 51), CAPD peritonitis was treated solely with vancomycin (continuous, n = 21; intermittent, n = 30). Clinical resolution was seen in all patients, requiring a mean of 3.2 days for macroscopic clearing of dialysate effluent. Recurrence of peritonitis within 1 month of cessation of therapy was unusual and did not vary between treatment protocols (4/21 v 3/30; P = NS). There were no differences in observed side effects. Thus, IP vancomycin proved to be a useful single agent therapy for gram positive and no organism CAPD peritonitis. Therapy with two IP doses was effective and as safe as continuous IP vancomycin therapy, and therefore should replace other vancomycin administration schedules in the treatment of CAPD peritonitis.

Drug Administration Schedule↗

Cytomegalovirus infection complicating renal transplantation and its relationship to acute transplant glomerulopathy.

The incidence of cytomegalovirus (CMV) infection was established, using laboratory criteria, in 298 patients receiving 362 renal allografts (164/298 = 55%). The incidence of CMV infection did not differ between azathioprine/prednisolone-treated and cyclosporine-treated patients (55% vs. 57% NS). The use of antithymocyte globulin (ATG) increased the incidence of CMV infection (78% vs. 51%: P less than 0.01). Donor and recipient CMV status, known for 116 allografts, did not correlate with the incidence of CMV infection (recipient CMV-positive = 50%; recipient CMV-negative = 54%: NS). CMV infection was responsible for 8 patients' deaths (2.7% mortality). Thirty-three patients with acute transplant glomerulopathy were identified (11%). There was no correlation between acute transplant glomerulopathy and CMV infection. Glomerulopathy was associated with poor graft survival (22/33 patients with a graft survival of less than 6 months). Thus CMV infection, although a common complication of renal transplantation with significant morbidity and mortality, is not closely associated with acute transplant glomerulopathy. Further, the lack of correlation of donor-recipient CMV serologic status with graft outcome limits the usefulness of pretransplantation donor screening.

Acute Disease↗

Corticosteroid agents in renal disease.

Corticosteroid agents have a major role in the treatment of several renal disorders which have an immune basis. They remain the treatment of choice for minimal-change glomerulonephritis, inducing remission in over 90% of patients. The role of corticosteroid therapy in patients with membranous glomerulonephritis remains controversial, although an extensive controlled trial indicated benefit from a two-month course of alternate-day therapy. Intravenously-administered methylprednisolone has been shown to benefit rapidly progressive crescentic glomerulonephritis; the benefit is probably comparable to that which is obtained with immunosuppression and plasma exchange. Corticosteroid therapy has improved dramatically the prognosis of glomerulonephritis that is associated with systemic lupus erythematosus and the various forms of vasculitis (excluding Wegener's granulomatosis), although the concomitant use of immunosuppressive therapy in these disorders reduces the required doses of corticosteroid drugs. For the last 20 years prednisolone and azathioprine have been standard therapy to prevent renal allograft rejection. However, corticosteroid agents are used currently in much lower doses or have been replaced by cyclosporin A.

Adrenal Cortex Hormones↗

Normal human serum also contains the lymphotoxin found in minimal change nephropathy.

We have studied serum-borne lymphotoxic activity in a large patient group with various forms of glomerulonephritis (GN). A potent inhibitor of lymphocyte blastogenesis was frequently demonstrable not only in patients with active minimal change nephropathy as has been previously described, but also in other forms of GN. The inhibitor was resistant to heating and prolonged storage but rendered ineffective by normal serum. We have been able to show for the first time, using gel filtration, that normal serum also contains the inhibitor. The inhibitor was shown to be highly avid for a receptor on leucocytes as judged by dose response experiments and by the ability of cell pellets to remove this activity. Gel filtration demonstrated a molecular weight in the range 60 to 160 kilodaltons. The combination of information regarding the biological properties of the inhibitor, its clinical occurrence and molecular weight suggests it to be distinct from any other well-described lymphotoxin. It's presence in normal serum in association with a self-regulatory factor and the known proclivity of minimal change nephropathy patients to infection, also indicate that the inhibitor may play an important role in immunoregulation.

Cell Division↗

Severe visceral disease in subacute cutaneous lupus erythematosus.

Subacute cutaneous lupus erythematosus has been heralded as a marker of relatively benign subset of systemic lupus erythematosus. In this article, we describe two cases with severe visceral disease and suggest that it may be less reliable as a predictor of benign disease than was previously accepted.

Adult↗

Clinicopathological associations in mesangial IgA nephropathy.

On hundred and fifteen renal biopsies performed in 112 patients with mesangial IgA nephropathy were reviewed and the histological disease patterns correlated with the clinical features at the time of initial biopsy. To determine the significance of macroscopic haematuria in this disease, specific comparisons were made between patients with a history of episodes of macroscopic haematuria and those with only microscopic haematuria. The mean age at initial biopsy was 38.3 years (90 males, mean 40.3 years; 22 females, mean 30.2 years). Histological examination showed 9 patients (8%) with class I disease (mesangial matrix expansion alone); 43 patients (38%) with class II disease (diffuse mesangial proliferation); 60 patients (54%) with class III disease (focal and segmental proliferation), including subsets of 20 patients (16%) with segmental sclerosis and/or synechiae and 23 patients (21%) with crescent formation. Class III disease and crescent formation correlated with an increased frequency of capillary loop IgA and glomerular fibrin deposition and with the presence of subendothelial and subepithelial deposits. The degree of renal impairment and the incidence of hypertension were increased in class III disease. Macroscopic haematuria patients were younger (mean 31.1 vs. 43.0 years; p less than 0.001), had less severe renal impairment (mean creatinine 116.2 vs. 213.3 mumol/l; p less than 0.001) and less class III disease (48 vs. 58%; p less than 0.05). The incidence of crescentic disease was equal in macroscopic (17%) and microscopic (23%) haematuria. Eventual progression to end-stage renal failure occurred in 12 patients (11%) and correlated with crescentic disease, renal impairment, hypertension and heavy proteinuria at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparison of fibrinolytic and defibrinating agents in established experimental glomerulonephritis.

The effect of fibrinolysis with Streptokinase and defibrination with Ancrod on the progression of established fibrin-related glomerular injury was assessed in rabbits developing anti-glomerular basement membrane antibody-induced glomerulonephritis. Untreated rabbits developed renal failure and a severe crescentic nephritis with prominent fibrin deposition after 5 days. Rabbits with established injury and glomerular fibrin deposition were treated with Streptokinase or Ancrod over the last 4 days of this model. Both treatments resulted in significant protection from loss of renal function and reduced crescent formation by day 5. Glomerular fibrin deposition was also significantly reduced by both agents, although Streptokinase produced a greater reduction than Ancrod. Two further groups of rabbits with advanced disease, were treated over the last two days of this model. Although treatment reduced glomerular fibrin deposition, no protection from loss of renal function was observed. These studies indicate that both treatments were effective, if used early, in preserving renal function in established fibrin related glomerulonephritis, but they did not effect the outcome of more advanced disease. Both agents prevented further glomerular fibrin deposition, although only early treatment with Streptokinase reduced glomerular fibrin to below pre-treatment levels.

Ancrod↗

Life-threatening sepsis complicating heavy metal chelation therapy with desferrioxamine.

A case of severe Yersinia enterocolitica septicemia in a hemodialysis patient receiving desferrioxamine (DFX) therapy is reported. The association between systemic yersiniosis and DFX chelation therapy is reviewed. The increasing application of DFX chelation, in iron overload states and for aluminium overload in dialysis patients, provides an increasing number of patients at risk for this unusual drug side effect. An awareness of the association between Yersinia sepsis and DFX therapy allows appropriate therapeutic intervention which may prove lifesaving.

Adult↗

The clinical spectrum of acute glomerulonephritis and lung haemorrhage (Goodpasture's syndrome).

The aetiology, clinical features and outcome of 40 patients presenting with Goodpasture's syndrome (glomerulonephritis with haemoptysis and pulmonary infiltrates) are reviewed. The diseases of the patients studied could be divided into three groups: antiglomerular basement membrane (anti-GBM) antibody-induced disease (7/40); systemic vasculitis (22/40) and idiopathic Goodpasture's syndrome (i.e. no systemic disease or anti-GBM antibody detected) (11/40). Overall mortality was 57.5 per cent (anti-GBM disease 4/7; systemic vasculitis 15/22; and idiopathic Goodpasture's syndrome 4/11). Most patients died of disease progression or infection. End-stage renal failure developed in 26 patients (anti-GBM (7), vasculitis (14) and idiopathic Goodpasture's syndrome (5). End-stage renal failure developed in 23 of 24 patients presenting with a creatinine of greater than 600 microM/l regardless of the aetiology of Goodpasture's syndrome or treatment used. Review of renal histology showed that all had proliferative nephritis, with 80 per cent of patients having more than 30 per cent crescents. Thus Goodpasture's syndrome was associated with a wide variety of underlying disease. It had a poor prognosis, with the degree of renal impairment at presentation, the extent of crescent formation and the nature of the underlying disease being the major determinants of outcome.

Adult↗

Renal involvement in systemic lupus erythematosus.

A review of 28 cases of biopsy-proven lupus nephritis seen in Prince Henry's Hospital, Melbourne, in the last 12 years from 1971 to 1982 is reported. The mean follow-up period was 51 months. Renal histopathological changes were categorized according to the WHO classification of lupus nephritis. The majority of our patient population fell into two of the seven possible histological subgroups - Class IV (diffuse proliferative) disease (53.6%) and Class IIb (mesangial proliferative) disease (28.5%). Treatment with prednisolone alone or with a prednisolone/azathioprine combination resulted in an equal five-year survival (82%) and a similar overall preservation of renal function. The major single cause of death was opportunistic infection (60%). Despite overrepresentation of the more severe forms of lupus nephritis in a nephrology-unit population, there was a satisfactory outcome from therapy with either prednisolone alone or with a prenisolone /azathioprine combination. However, there were significant rates of morbidity and death associated with immunosuppressive therapy, primarily from opportunistic infection.

Acute Kidney Injury↗

"Long-term" survival in light-chain myeloma with dialysis therapy alone.

We report a case of a 59 year old woman who presented in end-stage renal failure with lambda (lambda) light-chain myeloma (LLCM). Despite a large tumour burden, and refusal to accept cytotoxic chemotherapy, she was commenced on continuous ambulatory peritoneal dialysis (CAPD). With dialysis therapy alone she has shown considerable hematological improvement and remains well 18 months after diagnosis. The extremely poor prognosis attributed to light-chain myeloma is largely due to death from uremia. As the natural history of this disease in patients offered dialysis therapy is unknown, dialysis should not automatically be withheld from patients with LLCM.

Bone Neoplasms↗

Composition of interstitial cellular infiltrate identified by monoclonal antibodies in renal biopsies of rejecting human renal allografts.

Monoclonal antibodies and a four-layer immunoperoxidase technique were used to analyze and quantitate the various infiltrating cell types found in percutaneous renal biopsies of 25 patients undergoing acute renal allograft rejection. Cell markers included monoclonal antibodies to the human leukocyte-common antigen (PHM 1), mononuclear phagocytes (PHM 2, FMC 32), T cells and T cell subsets (OKT 3, OKT 4, and OKT 8), B cells (7.2), polymorphs (FMC 10, FMC 13), and plasma cells (OKT 10). The proportion of labelled interstitial cells was expressed as a percentage of the total number of infiltrating leukocytes identified with PHM 1, and correlated with the histologically graded intensity of rejection. In mild rejection 32% of the infiltrating cells were T lymphocytes, of which 90% were OKT-8-positive cytotoxic-suppressor cells, and 52% were macrophages. Similarly, in moderate rejection T cells composed 42% of the infiltrate (with 67% of T cells expressing OKT 8 antigen), and macrophages formed 38% of the total cells. By contrast, in severe rejection, the T cell component was decreased to 15% of the cells, of which 78% were OKT-8-positive; these were preponderantly macrophages (60%) and polymorphs (22%). These studies demonstrate that cytotoxic-suppressor T cells and macrophages are the major cells mediating acute interstitial graft rejection.

Antibodies, Monoclonal↗

Continuous ambulatory peritoneal dialysis (CAPD): an established treatment for endstage renal failure.

This paper is a study of 117 patients with endstage renal failure, treated by continuous ambulatory peritoneal dialysis (CAPD) over periods of 1-56 months. The study has shown CAPD to be an effective form of dialysis with a number of advantages over intermittent peritoneal dialysis and hemodialysis (better control of salt and water status, hypertension and anemia, steady state biochemistry and greater ease of self-dialysis). Peritoneal clearance and ultrafiltration have remained adequate in all but a few patients. Hypoproteinemia, poor nutrition, obesity and abdominal herniae have been problems in a small percentage of patients. Hyperlipidemia has developed in half the patients but improved with diet. Peritonitis remains the major barrier to the more widespread use of CAPD, although its incidence can be considerably reduced by use of better connectors, bacterial filters and choice of patients.

Adolescent↗

Involvement of the macrophage in experimental chronic immune complex glomerulonephritis.

Serial renal biopsies for glomerular culture, histochemical staining for beta-glucuronidase, electron microscopy (EM) and light microscopy, were used to study macrophage involvement in experimental chronic immune complex (IC) glomerulonephritis (GN) induced in rabbits by daily intravenous injections of bovine serum albumin (BSA). In the 26 animals studied, proliferative GN of variable severity was induced, with mild disease in 5 animals, moderate proliferation in 15 and crescentic GN in 6. Macrophages first appeared in glomerular culture outgrowths during the 2nd and 3rd weeks, coincident with the onset of proteinuria and rising serum creatinine concentration. Large numbers of macrophages (in excess of 20 per glomerulus) were seen by the 5th weeks and persisted to the 9th week. The number of macrophages in outgrowths was not significantly greater in animals with crescentic disease. EM demonstrated macrophages in capillary loops, and in glomeruli with crescents, macrophages could be seen in the urinary space. Histochemical staining for beta-glucuronidase also demonstrated macrophages in the glomerular tuft and in crescents when present. These results indicate that macrophages constitute a considerable proportion of the glomerular hypercellularity seen in chronic IC glomerulonephritis.

Animals↗