Argentaffin and non-argentaffin carcinoid tumorurs of the appendix.

Tumours of the vermiform appendix were studied. The majority proved to be carcinoid tumours of the usual argentaffin-positive type but a substantial minority, generally tumours of minute size, were found to have a somewhat different histological pattern and were argentaffinnegative. Some contained argyrophil granules. The non-argentaffin tumours are considered to form a subgroup of carcinoid tumours.

Incidence of thin membrane nephropathy: morphometric investigation of a population sample.

To explore the incidence of thin membrane nephropathy (thin basement membrane syndrome, benign familial haematuria), glomerular basement membrane thickness was assessed by light and electron microscopy and by morphometry in a series of newly transplanted allograft kidneys, in lieu of normal kidney specimens. Five of the 76 donors possessed an abnormally thin basement membrane, similar to that observed in thin membrane nephropathy, while in two others the measurements fell in the overlap range between thin and normal. Seven donors therefore had a definite or possible basement membrane lesion. After taking account of an additional series of controls, unrelated to transplantation, it is suggested that the incidence of this abnormality in the general population lies between 5.2% and 9.2%. Circumstances did not allow any association between a thin basement membrane and haematuria or other clinical manifestations to be detected.

Accidental transplantation of bronchial carcinoma from a cadaver donor to two recipients of renal allografts.

Malignancy was transferred inadvertently to two patients, each of whom received a renal transplant from a cadaver donor who was found at necropsy to have a small, clinically silent carcinoma of lung. Both recipients died with metastatic bronchial carcinoma of the same histological type as the donor's tumour. The literature on transplanted malignancy is reviewed.

Membranous glomerulonephritis in transplant kidneys: recurrent or de novo disease in four patients.

Membranous glomerulonephritis in the graft is a uncommon complication of renal transplantation. In the 4 cases we describe, one patient had recurrence of his original disease, but in the other 3 it arose de novo after allografting for focal segmental glomerulosclerosis, cystinuria or secondary amyloidosis. The lesion was accompanied by mesangial changes of lesser degree and by chronic rejection, and it resulted in accelerated loss of graft function. Transmission of host disease to the graft is more likely to occur in patients whose original membranous lesion progressed to renal failure relatively rapidly, while in de novo cases, the antecedent host disease seems often to have been focal segmental glomerulosclerosis. Allograft membranous glomerulonephritis may be less rare than hitherto supposed.

Measurement of glomerular basement membrane thickness and its application to the diagnosis of thin-membrane nephropathy.

Morphometry is a valuable diagnostic aid when the glomerular basement membrane is suspected of being abnormally thin. Determination of overall width by the harmonic mean method has been described in detail. Results were given of measurements in 20 control subjects with histologically normal basement membranes and 41 allograft kidneys. Mean +/- 1.5 SDs of a series was found to be the most useful empiric guide to basement membrane widths. It was confirmed that the membrane was thinner in females than in males. The lower end of the respective mean +/- 1.5 SDs range overlapped with thicknesses that occurred in "thin-membrane nephropathy" in women but not in men, although the threshold width below which hematuria was liable to occur was similar, at approximately 340 nm, in both sexes. It is suggested that the higher incidence of symptomatic thin-membrane nephropathy in females is related to their normally thinner glomerular basement membranes, in the context of the common threshold level. Other histologic findings, and the clinical picture, remain relevant to the diagnosis of thin-membrane diseases.

Experience in the diagnosis of glomerulonephritis using combined light microscopical, ultrastructural and immunofluorescence techniques--an analysis of 134 cases.

The contribution of electron and immunofluorescence microscopy to renal biopsy diagnosis is illustrated by the results obtained in a personal series of patients with various types of glomerulonephritis. Introductory notes on the ultrastructure of the glomerular capillary and on immunological processes are also included. Immunofluorescent staining has particular value in demonstrating IgG-containing deposits in early membranous glomerulonephritis at a stage when ordinary microscopy is inconclusive. It is capable of throwing light on the mechanism of glomerular damage in severe extracapillary proliferation and in some cases of recurrent haematuria, but is less successful in separating minimal change disease from proliferative processes. Electron microscopy reveals the precise site of immune deposits and fibrin together with basement membrane changes, the microtubular structures common in SLE, and other details. It is concluded that for the accurate diagnosis of kidney disease it is essential to supplement light microscopy by one, or preferably both these methods.

Malignant synovioma: electron microscopical findings in three patients and review of the literature.

Ultrastructural findings in three malignant synoviomas are described. Two typical "biphasic" tumours contained "epithelial" cells possessing filopodia or microvilli, specialised cell attachment and a basal lamina, and smaller "stromal" cells showing transitions to fibroblasts. In one case, the microvilli included fibrils resembling those in epithelial cells of the intestine and renal tubules. The third tumour was mainly spindle-celled with little epithelial differentiation and no clear division into cell types, but intracytoplasmic microfibrils were conspicuous, forming ovoid masses. The tumour cells differ a good deal from normal human synovial cells but some of the features of the neoplasm are found in inflamed human synovium and in normal synovial membranes of other species. The cytoplasmic fibrils in the third case are similar to those reported by others in epithelioid sarcoma, a tumour that may be of related origin to synovioma; however, the phenomenon may be merely degenerative.

Abnormally thin glomerular basement membranes associated with hematuria, proteinuria or renal failure in adults.

Clinical and pathologic findings are described in 14 patients whose main abnormality was an excessively thin glomerular basement membrane (GBM). The subjects were aged 11-51 years, the majority males: most were referred because of hematuria, but proteinuria was the main problem in 2, while hypertension or renal functional impairment was found in several, and 1 was in end-stage renal failure. A history of apparently similar renal symptoms was obtained in another 3 family members. In addition to GBM abnormalities, renal biopsy features included a slight mesangial matrix increase, occasional mesangial cell excess and often appreciable pedicel effacement. There were scanty electron-dense deposits. The mean thickness of the GBM varied from 206 to 301 nm, whereas in IgA nephropathy patients used as controls it was 356-464 nm. It is concluded that some of the lesions in adults are 'benign', and some progressive. 'Thin membrane nephropathy' is comparatively common among patients seen by the authors, and it is suggested that awareness of this condition will result more often in its recognition.

Kidney pathology in liver allograft recipients after long-term treatment with cyclosporin A.

Organ transplant recipients given immunosuppressive treatment with cyclosporin A are at risk of injury due to nephrotoxicity. Eight liver allografted patients whose renal function became impaired during therapy with cyclosporin A for up to 4.5 years were investigated by renal biopsy. Ischemic changes in glomeruli were found to be greater than in controls, and there was focal tubular atrophy, but an excess of lesions in small arteries could not be demonstrated. In one patient there were glomerular changes suggestive of thrombotic microangiopathy. Interstitial fibrosis and cellular infiltration were slight. The pathogenesis of the ischemia remains to be elucidated, but reasons are advanced for favoring the view that the mechanism of cyclosporin A nephrotoxicity is primarily vasomotor, causing a reduction of renal blood flow and glomerular filtration rate without permanent organic arterial narrowing; nephrons become damaged irreversibly nevertheless.

Immunopathology of penicillamine-induced glomerular disease.

Four patients with rheumatoid arthritis developed heavy proteinuria after 5 to 12 months of treatment with D-penicillamine. Light microscopy of renal biopsy samples showed minimal glomerular capillary wall thickening and mesangial matrix increase, or no departure from normal. Electron microscopy, however, revealed subepithelial electron-dense deposits, fusion of epithelial cell foot processes, and evidence of mesangial cell hyperactivity. Immunofluorescence microscopy demonstrated granular capillary wall deposits of IgG and C3. The findings were similar to those in early membranous glomerulonephritis, differences being observed however in the results of staining for the early-acting complement components Clq and C4. It is tentatively concluded that complement was activated by the classical pathway.

Budd Chiari syndrome from myosarcoma of right atrium.

A 50-year-old man presented with abdominal pain followed by marked liver and renal dysfunction. Although liver scan appearances were not diagnostic, at laparotomy a tense, enlarged liver was found with thrombosis of the inferior vena cava. Despite full supportive measures the patient died within a month of laparotomy. Subsequent necropsy confirmed the diagnosis of Budd Chiari syndrome and revealed the primary cause to be a myosarcoma of the right atrium, an occurrence hitherto unreported.

Fine structure of a neuroendocrine complex in the mucosa of the appendix.

The fine structure of a neuroendocrine complex within the lamina propria of the human appendix is described. This complex contains four types of neurosecretory cells, occasional neurons, Schwann cells, and numerous nerve processes, including axons with varicose swellings. Few of the axons form true synapses, but many make some junctional contact with the neurosecretory cells and with other nerve processes. From the morphology of their vesicles, most of the nerve fibers appear to belong to the peptidergic component of the enteric nervous system. The mucosal neuroendocrine complex appears to be an integral part of the mucosal nervous plexus.

Immunopathology of penicillamine-induced glomerular disease.

Four patients with rheumatoid arthritis developed heavy proteinuria after five to 12 months of treatment with D-penicillamine. Light microscopy of renal biopsy samples showed minimal glomerular capillary wall thickening and mesangial matrix increase, or no departure from normal. Electron microscopy, however, revealed subepithelial electron-dense deposits, fusion of epithelial cell foot processes, and evidence of mesangial cell hyperactivity. Immunofluorescence microscopy demonstrated granular capillary wall deposits of IgG and C3. The findings were similar to those in early membranous glomerulonephritis, differences being observed however in the results of staining for the early-acting complement components C1q and C4. It is tentatively concluded that complement was activated by the classical pathway.

Pneumococcal antigen in pneumonia. A post-mortem study with the histological and bacteriological findings.

Pneumococcal capsular antigens can be detected in lung tissue by counter-current immunoelectrophoresis even when, following antibiotics, post-mortem bacterilogy suggests that Escherichia coli has replaced pneumococci. The results suggest that antipneumococcal therapy would benefit at least 55% of patients critically ill with lung infection and that the potentially toxic drugs directed at coliform bacteria may be unnecessary.

Tubo-ovarian actinomycosis associated with intrauterine contraceptive devices.

PIP: Case reports of 2 patients, 26- and 28-years-old, respectively, with actinomycosis of the uterine adnexa, a relatively rare site of involvement, are presented. At the time symptoms developed, one patient had a copper-7 IUD in situ while the other had recently had a Lippes loop removed. Neither patient showed evidence of spread of infection from a lesion of bowel. It is suggested that the reducing properties of the copper in an IUD might produce an environment favorable to anaerobic arganisms.^ieng

Insulin as an amyloid-fibril protein at sites of repeated insulin injections in a diabetic patient.

A patient with Type 1 (insulin-dependent) diabetes mellitus developed localised amyloidosis at the sites of his injections of porcine insulin. A major amyloid fibril protein was extracted and, by means of its amino acid composition and amino acid sequence, it was shown to contain intact insulin molecules. Porcine insulin is the tenth protein and the first foreign protein to be chemically identified in human amyloid fibrils.

Reactivity of monoclonal antibody P1 with glomerular basement membrane in thin-membrane nephropathy.

A monoclonal antibody, P1, possessing antiglomerular basement membrane specificity similar to that of naturally-occurring Goodpasture antibody, was used to study renal biopsy material from patients with thin-membrane nephropathy. Immunofluorescence and immunoperoxidase techniques were employed to detect tissue localisation after sections had been incubated with P1. Staining of glomerular and tubular basement membranes in the 14 patients with thin-membrane nephropathy was similar to that in 10 subjects with various other renal diseases, whereas three patients with Alport's syndrome all gave diminished or absent staining, as has been reported previously. These observations confirm that Goodpasture antigen is present in the basement membranes in thin-membrane nephropathy and that it reacts normally with P1 antibody. They also add to the evidence that the lesions of thin-membrane nephropathy and Alport's syndrome are fundamentally different. The staining method may be used as a differential diagnostic test.