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Biomedical subjects

D R Turner

Publications and source records attributed to D R Turner.

At least 127 records · Page 7Linked to original sources

Focal segmental glomerulosclerosis with rapid decline in renal function ("malignant FSGS").

We describe 11 patients whose renal biopsies showed minimal changes with focal segmental glomerulosclerosis. These patients, in contrast to the majority of patients with similar renal histology, went into renal failure within 2 1/2 years of clinical onset. All were young, severely nephrotic, most hypertensive, with microscopic hematuria, non-selective proteinuria and extreme hypercholesterolemia. Treatment with corticosteroids and cytotoxic drugs was without effect in any patient. Despite rapid decline in renal function, profuse proteinuria and a nephrotic syndrome persisted into terminal uremia and continued even after dialysis had begun. Seven patients were given nine allografts; four grafts failed because of immediate vascular complications, and a persistant nephrotic syndrome was evident in two of the five surviving grafts. This did not, however, lead to graft failure. Two patients died on dialysis because of myocardial problems. These patients with rapid decline in renal function constitute a distinct clinical subgroup amongst those with focal and segmental glomerulosclerosis; it is possible that they have a different primarily vascular pathogenesis in contrast to other patients with similar renal biopsy appearances.

Adolescent↗

Localization of glomerular "deposits" in Henoch--Schönlein nephritis.

Twenty-five renal biopsies from patients with Henoch--Schönlein nephritis were examined using light microscopy, immunofluorescence, 1 micrometer plastic-embedded sections and electron microscopy. The 1 micrometer plastic-embedded sections and electron microscopy showed deposits in mesangial, subendothelial and subepithelial sites. Some of the latter were very large and similar to those which have been described as "humps" in acute proliferative glomerulonephritis. Immunofluorescence showed the mesangial deposition of IgG, IgA and C3 with extension into a peripheral position in some cases. Fibrin was frequently found associated with crescents. The case for Henoch--Schönlein disease being mediated, in part at least, by immune complex deposition, is presented.

Complement System Proteins↗

Value of renal biopsy in acute intrinsic renal failure.

Eighty-four patients presented with acute renal failure and features suggesting a diagnosis of intrinsic renal disease other than "acute reversible renal failure." Renal biopsy proved valuable in establishing the diagnosis, in indicating the reversibility of the lesion, and in helping to decide on treatment.

Acute Kidney Injury↗

Mesangial cell cytoplasm and glomerular disease.

In this study we have examined mesangial cell cytoplasm as seen by light microscopy of plastic embedded renal biopsy material. An assessment of mesangial cell morphology has been made in each of the 350 renal biopsies, and this has been correlated with the disease process. A surprisingly close correlation with the type of disease present was demonstrated. Thus it appears that an increase in mesangial cell cytoplasm correlates with an active process involving the mesangial area. It is suggested that the index of mesangial cell reactivity may be useful in diagnosis of glomerular disease processes.

Cytoplasm↗

Transplantation in mesangiocapillary glomerulonephritis with intramembranous dense "deposits": recurrence of disease.

Six patients with mesangiocapillary glomerulonephritis and intramembranous dense "deposits" developed terminal renal failure and were transplanted, three from living and three from cadaver donors. Eight renal biopsy specimens were obtained from five of the grafts, from 1 to 26 months following transplantation. All six biopsy specimens taken later than seven months following the graft showed recurrence of dense intramembranous "deposits" in the basement membranes of glomeruli, and of Bowman's capsule and tubular basement in five. Recurrence of "deposits" was associated with deposition of C3 on immunofluorescent study in all but one specimen; in addition, IgM was found in two specimens, but IgG and early complement components were absent. Only two patients, however, showed glomerular proliferation associated with profuse proteinuria. In the other subjects the recurrence of the "deposit" was not associated with clinical findings. Graft loss, which occurred in two patients, was predominantly from rejection.

Adult↗

Mesangiocapillary glomerulonephritis with dense "deposits" in the basement membranes of the kidney.

Amongst 125 patients with mesangiocapillary glomerulonephritis (MCGN), 19 showed continuous intramembranous dense "deposits" (IDD). Most were children or young adults. Two patients had partial lipodystrophy. Eleven had a consistently low plasma concentration of C3; only three, however, had an initial low plasma concentration of C4, which rose and then remained normal in two. Tests for the C3 nephritic factor were positive in thirteen patients, and plasma C1q was normal in 8 out of 11 cases investigated. Ten out of twelve (seven of them with low plasma C3) showed C3 deposition by immunofluorescence in the glomerular tuft. This was also demonstrated in some instances in Bowman's capsule and tubular basement membranes. Stains for IgG, IgA, C4 and C1q were negative in all, whereas stains for IgM and fibrin were weakly positive in the glomeruli of three and eight cases repectively. Eight patients went into terminal renal failure over an average of thirty-three months and required hemodialysis or transplantation. MCGN with IDD is an uncommon pattern of renal response to injury, which involves activation of the alternate pathway of the complement system and has a poor short term prognosis. The association with partial lipodystrophy and C3-splitting activity suggests a primary complement abnormality.

Adolescent↗

Phagocytes, lipid-removal and regression of atheroma.

Reticuloendothelial (RE) phagocytes (macrophages and histiocytes) can be distinguished from locally-derived lipid-containing cells (e.g., arterial smooth muscle) or locally derived phagocytes (e.g., Schwann cells and microglia) by the demonstration of a diffuse catalase reaction in a proportion of these RE cells with a short incubation modification of the Novikoff-Golfischer diaminobenzidine histochemical methods. Even though only a proportion of an RE population is catalase-positive, the results accord with the majority of current opinion that most of the cells in atherosclerotic lesions are derived locally, whereas the phagocytes in lipid implants and xanthomas are of RE origin. The phagocytes in the peripheral nerve undergoing Wallerian degeneration appear to be of mixed RE and endogenous origin, whereas microglia around multiple sclerosis plaques seem to be derived locally. Lipid in lesions with RE phagocytes (subcutaneous lipid implants and xanthomas) is relatively rapidly resorbed, whereas lipid in lesions with few RE phagocytes (atherosclerosis) or phagocytes of endogenous origin (CNS degeneration) is more slowly resorbed or partly retained within the tissue. Wallerian degeneration in the peripheral nerve, with its mixed population of RE and endogenous phagocytes, occupies an intermediate position in the speed of lipid removal.

Adult↗

Membranous nephropathy. Long-term follow-up and association with neoplasia.

Sixty-six patients of all ages whose renal biopsy appearances satisfied strict criteria for the histopathological diagnosis of membranous nephropathy were studied and followed for a mean of 5-4 years (range 1 to 20 years). From initial investigation seven patients were found to have associated neoplasia, and in two patients the condition followed treatment with a mercurial diuretic and gold. One patient was Australia antigen positive. Two patients developed renal vein thrombosis, but in both this appeared to follow not precede their nephrotic syndrome. In the remaining 56 patients there was no associated factor. During the follow-up period, approximately one-quarter of the patients (15) died, nine from renal failure; one-quarter (10) had a persistent nephrotic syndrome, another one-quarter (15) proteinuria of lesser degree. The final one-quarter (16) are now in complete remission. The prognosis of the 54 patients with an initial nephrotic syndrome was poorer than the 12 with lesser proteinuria and no oedema at onset; five of 11 children were in complete remission when last seen. All but one of the nine patients who developed terminal chronic renal failure 4 to 18 years from onset had an unremitting nephrotic syndrome, eight of the 10 currently alive with a persistent nephrotic syndrome have reduced renal function. Renal functional deterioration did not occur in the absence of proteinuria. There was only slight correspondence between the stage of biopsy appearance, glomerular filtration rate at time of biopsy, time of the biopsy from apparent onset, or status at last follow-up. Staging is therefore of limited prognostic value. Twenty-two patients were treated with corticosteroids for 2 to 36 months; we detected no short or long-term benefit when compared to patients not so treated.

Adolescent↗

Plasma C3 and C4 concentrations in management of glomerulonephritis.

As part of a larger study of serial complement profiles in glomerulonephritis plasma C3 and C4 concentrations were measured using commercially available immunodiffusion plates. A total of 303 samples were obtained from 128 patients suffering from forms of nephritis associated with hypocomplementaemia-namely, lupus nephritis, mesangiocapillary glomerulonephritis (M.C.G.N.), and acute glomerulonephritis.These simple measurements of C3 and C4 gave clinically useful information. In lupus nephritis C3 and C4 generally correlated and C4 concentrations were more often and more profoundly depressed than C3 concentrations. Neither C3 nor C4 concentrations alone correlated well with the antinuclear factor titre.In both acute glomerulonephritis and M.C.G.N. the C3 concentrations were frequently lower than 20% of normal (which was never the case in patients with lupus), while the C4 concentration was usually normal and was almost never depressed in the absence of C3 depression. This suggests activation of complement at the C3 level by the "bypass" pathway in acute nephritis as well as in M.C.G.N., though both may be operating in some patients. In acute glomerulonephritis but not in M.C.G.N. C3 concentrations returned to normal within eight to 12 weeks.The two varieties of M.C.G.N. identified by the site of the deposits in the capillary glomerular walls differed in their C3 levels. In 10 patients with intramembranous dense linear deposits the C3 was always low over very long periods of time, rising in three out of four patients only after transplantation and immunosuppression. Other patients with M.C.G.N., in contrast, often showed normal C3 concentrations. Concentrations of C4 did not differ in either group, being normal in 80% of samples from all types.

Antibodies, Antinuclear↗