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A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.

Interleukin 4 (IL-4) receptors were detected by a monoclonal antibody on tumor cells of 10 of 29 squamous cell carcinomas and 6 of 17 adenocarcinomas of the lung. None of the small cell carcinomas or carcinoid tumors stained. Parallel sections stained for epidermal growth factor receptors showed that all but 2 of the IL-4 receptor-positive tumors also expressed epidermal growth factor receptors. Positive labeling for IL-4 receptors was also obtained on nonneoplastic bronchial epithelium and on lymphocytes and macrophages infiltrating the tumor stroma. The role of IL-4 and its receptor in normal human lung is unknown, but the expression of IL-4 receptors on particular subtypes of lung tumors suggests that they may have a role in differentiation or proliferation of squamous and adenocarcinomas.

The renal biopsy findings in 40 patients with segmental glomerulonephritis are reported. The term is used to describe a condition in which one or more segments of the glomerular tuft is involved by disease when other segments appear unaffected on light microscopy. The word 'focal' is not used as it may be taken to imply that the changes affect some glomeruli but not others and the evidence for this is not convincing. Segmental glomerulonephritis was a relatively common finding in cases of proteinuria with or without the nephrotic syndrome. The severity of the glomerular changes did not correlate with the ultimate prognosis. On the other hand the tubular and interstitial changes, as assessed by a grading procedure and by point counting, were significantly less severe in those patients who showed clinical recovery than in those who did not.

In the period 1968-76, necropsies were carried out on 30 patients who had been treated by long-term intermittent maintenance haemodialysis. Fourteen of these patients developed bilateral cystic disease of the kidney. Clinical, pathological, and radiological investigation of these patients when they first presented did not reveal any evidence of renal cystic change. The main complications of this condition are haemorrhage and tumour formation. Six patients developed renal tumours, and in five cases these were multiple. The histological appearance of these neoplasms gave no indication as to whether they would behave in an aggressive manner. One patient died of metastatic carcinomatosis from a renal primary. The condition of acquired cystic disease of the kidney should be suspected if patients on maintenance haemodialysis suffer from recurrent haematuria or are found to have enlarging kidneys.

The clinical and pathological findings are reviewed in ten cases where renal biopsy showed abnormalities predominantly within the interstitium. In six the nephritis was considered to be drug-induced; in two the aetiology was slightly obscure but the most likely diagnosis was considered to be sarcoidosis. Of the remaining two cases one was chronic pyelonephritis and the other polyarteritis nodosa. The diagnosis and pathogenesis of the renal lesions are discussed and attention is drawn to the importance of distinguishing primary interstitial changes from those found in association with glomerular disease.

Ninety four pulmonary neoplasms were examined immunocytochemically with two or three different monoclonal antibodies against the intermediate filament proteins cytokeratin, neurofilament, vimentin, and desmin. In normal tissues these have a different and non-overlapping distribution, and it is generally believed that tumours maintain the same pattern of expression as the tissues from which they arise. In this report, however, the coexpression of at least two (and less commonly three or four) different intermediate filaments was seen in 40% (37 of 94) of the cases of lung cancer. These results, especially if confirmed in other common types of human malignancy, have considerable implications for the use of anti-intermediate filament antibodies in diagnostic pathology.

Lung lavage was performed in 16 anaesthetized rabbits to produce surfactant-deficient lungs. This resulted in alveolar collapse, an arterial PO2 of less than 15 kPa on 100% oxygen and an inflection point on the inspiratory limb of the pressure-volume curve at an airway pressure of 8-10 mm Hg. One group of eight animals was then ventilated with a positive end-expiratory pressure (PEEP) equal to the pressure at the inflection point, whilst the second group of eight was ventilated with a PEEP 5 mm Hg less than the inflection point. Animals in the high PEEP group had a significantly greater arterial PO2 than those in the low PEEP group, but the mean survival time for each group was similar. However, there was a significantly greater incidence of hyaline membranes in the low PEEP group. Various mechanisms to explain these findings are discussed.

From 1976 to 1982 five patients undergoing haemodialysis at Oxford Renal Unit suffered serious complications from acquired cystic disease of the kidney and two died as a direct result. Clinical features seen were pain, haematuria, palpable renal enlargement, massive haemorrhage, resolution of anaemia, and metastatic malignancy. The clinical histories emphasise the features of a disease that is likely to assume increasing importance in patients undergoing haemodialysis.

The histology of renal allografts was compared in a series of 107 biopsies from patients receiving cyclosporin and 126 biopsies from patients receiving azathioprine and prednisolone. Patients receiving cyclosporin were converted to azathioprine and prednisolone 90 days after transplantation. Biopsies were taken routinely at 7, 21, 90, and 365 days, irrespective of clinical graft function and were examined "blind" by two independent observers. Interstitial haemorrhage was more common in patients treated with azathioprine and prednisolone corresponding with their poorer graft survival. Analysis of glomerular, tubular, vascular, and interstitial changes showed no other important differences between the two groups despite clinical evidence of reversible cyclosporin nephrotoxicity. Quantitation of interstitial fibrosis in 90 day biopsies showed it to be equal in prevalence after treatment with azathioprine and prednisolone and cyclosporin. It was preceded by diffuse interstitial cellular infiltration, a common finding in early biopsies. Diffuse cellular infiltrates were generally associated with higher serum creatinine concentrations and, if persistent, a poorer graft prognosis than focal infiltrates, but they were not always associated with renal dysfunction.

A panel of seven monoclonal antiepithelial antibodies of different specificities, including anticytokeratin, human milk fat globule membrane, C, and carcinoembryonic antigen (CEA) were used with the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique to determine their value in the differentiation between benign and malignant mesothelial cells and lung carcinoma in histological preparations. The anticytokeratin antibody reacted strongly with all cases of reactive mesothelium, mesothelioma, and lung carcinoma. Antibodies to human milk fat globule membrane and the Ca antigen stained mesothelioma and carcinoma and 43% of cases of reactive mesothelium. Staining for carcinoembryonic antigen was not detected in reactive mesothelium or mesothelioma, but was present in most of the lung carcinomas. CEA seemed to be the single most useful marker in distinguishing carcinoma from mesothelioma in that a positive reaction for CEA would indicate carcinoma rather than mesothelioma.

The results of immunoperoxidase staining of 33 routinely processed renal biopsies correlated with the results of direct immunofluorescence in 79% of tests performed. Most of the discrepant results were due to positive immunoperoxidase staining, possibly reflecting greater sensitivity of the method. A comparison of two immunoperoxidase methods showed that the indirect method produced less intense staining than the peroxidase-antiperoxidase (PAP) method when equivalent primary antibody titres were used. Lowering the primary antibody titres for the indirect technique resulted in equivalent staining by the two methods. Predigestion by protease VII effectively revealed the antigens under study without causing tissue damage or section loss.

The distribution of fibronectin in 42 renal biopsies was investigated using an indirect immunoperoxidase technique on paraffin sections of formalin-fixed material. Biopsies were obtained from normal human kidneys and from patients with a variety of glomerular disorders. In normal glomeruli, fibronectin was present in Bowman's capsule, in the mesangium, and outlining peripheral capillary loops. A significant increase in fibronectin was observed in most types of glomerulopathy with a distribution closely related to the histopathological diagnosis. Fibronectin was diminished or absent in segmental scars, old diabetic nodules, and hyalinised glomeruli.

One hundred and four surgically resected lung tumours were labelled in either cryostat or freeze dried sections with a monoclonal antibody (Ki67), which reacts with a nuclear antigen expressed by proliferating cells. The tumours were categorised semiquantitatively into four proliferative grades, a classification that can be performed rapidly and reproducibly by the pathologist. In keeping with previous cell kinetic studies all small cell carcinomas had high proliferation rates, whereas the carcinoid tumours were in the lowest grade. In contrast, the adenocarcinomas (27 cases) and squamous cell carcinomas (63 cases) varied widely in their proliferative state, in keeping with their heterogeneous, morphological, and clinical behaviour. Immunocytochemical labelling of lung tumour biopsy specimens with antibody Ki67 is a simple technique within the scope of routine surgical pathology laboratories, which might enable these tumours to be classified according to their proliferative status and treatment to be selected accordingly.

Cytology and histology are correlated in a series of 22 cases chosen to illustrate the differential diagnosis between clusters of benign bronchial or bronchiolar cells seen in sputum, and those of alveolar cell carcinoma or adenocarcinoma with alveolar spread. Alveolar-cell carcinoma is characterised by clusters of small epithelial cells in spherical or irregular formations, none showing enough polarity to distinguish a smooth or palisaded surface. The appearances are most distinctive if vacuolation is absent. The diagnosis cannot, however, be confidently made in all cases from morphological features of cells in sputum.

Saline lavage of the lungs of eight anaesthetized New Zealand White rabbits was performed to produce a surfactant-depletion model of the neonatal respiratory distress syndrome. A characteristic change in the shape of the pressure-volume curve occurred, with the appearance of an inflection point on the inspiratory limb. The animals were treated with high frequency oscillation (HFO) at 15 Hz and the results compared with those of a previously studied group of eight similar rabbits treated with controlled mechanical ventilation (CMV) with end-expiratory pressure equal to the pressure at the inflection point, but with the same mean airway pressure of 15 mm Hg. The animals treated with HFO had significantly higher arterial oxygen tensions and end-expiratory lung volumes than those treated with CMV, but there was no significant difference between hyaline membrane scores. Although there was no significant difference in mean survival times, five of the HFO treated animals showed reversion of the shape of their pressure-volume curves towards the prelavage configuration, suggesting a recovery of surfactant function.

Six female patients with systemic lupus erythematosus (S.L.E.) have been treated with chlorambucil. In five the decision was taken after failure by corticosteroids to control progressive renal disease in the face of unacceptable corticosteroid toxicity. After the introduction of chlorambucil renal function improved and all patients remain well six, six, five, three, and two-and-a-half years later, respectively. On renal biopsy five had focal proliferative glomerulonephritis. Repeat biopsy in two cases showed quantitative improvement. The sixth patient was treated with chlorambucil because of failure by corticosteroids to control peripheral vascular lesions and haemolysis and she remains well four years later. In four patients is it probable that amenorrhoea was related to chlorambucil treatment, but there were no other important side effects although one patient developed a degree of marrow depression during treatment. Chlorambucil may hold advantages over the immunosuppressive drugs normally recommended in this condition, azathioprine and cyclophosphamide, as it appears less liable to cause important marrow suppression and, unlike cyclophosphamide is not associated with alopecia and haemorrhagic cystitis.

The morbid anatomical factors in the production of right heart hypertrophy and failure in emphysema have been reviewed with reference to 44 cases studied by standard histological methods and by post-mortem pulmonary arteriography. The most important factors in raising the pulmonary vascular resistance in these cases are considered to be vascular deformity and pressure by the emphysematous spaces on the adjacent branches of the pulmonary artery. Precapillary bronchopulmonary arterial anastomoses may be of importance in those cases where areas of localized bronchiectasis are present. Intimal fibrosis of the pulmonary arterioles, destruction of the pulmonary vascular bed, and thromboembolic phenomena were thought to be of only minor importance in the production of cor pulmonale in emphysema.

Toxemia was induced in 13 of 20 pregnant ewes by the stress of a change in environment and food deprivation late in pregnancy. Of the toxemic ewes, eight developed prominent neurological findings with convulsions, motor weakness, and blindness, whereas five ewes developed azotemia without neurological signs. Proteinuria and azotemia occurred in all but one of the toxemic animals. Seven animals did not develop clinical or laboratory evidence of toxemia. Hypertension did not occur with the onset of toxemia but all toxemic animals showed glomerular changes by light and electron microscopy. These abnormalities, which were similar to those seen in human preeclampsia, included endothelial cell swelling, focal reduplication of the basement membrane, and fusion of the epithelial cell foot processes. The toxemia could not be attributed to changes in hematocrit, plasma glucose, Na, Cl, CO(2), K, Ca, fibrinogen, arterial pH, lactate, or pyruvate concentrations. Cardiac output fell only in ewes with prominent neurological signs. Plasma renin rose strikingly in animals developing toxemia, without change in substrate concentration. In contrast to human and other species, sheep uterus and amniotic fluid contained no detectable quantities of renin. Thus in response to stress the pregnant ewe develops a toxemia which in the absence of hypertension has clinical and pathological similarities to human preeclampsia.

A simple method is described for the quantitative examination of small intestinal mucosal biopsies involving the determination of an index related to the surface-to-volume ratio of the mucosa. The method is of value in distinguishing minor degrees of villous abnormality and will prove useful in comparing serial changes in a given patient. It will also allow comparisons to be made between biopsies taken in different medical centres.

The pathological features of 20 cases dying in status asthmaticus have been studied. In gross sections the lungs showed no emphysema, but mucus plugs in the air passages and focal areas of collapse were outstanding features. Five cases showed cystic bronchiectasis which was of a similar distribution to the focal areas of collapse, occurring in the upper lobes as commonly as in the lower lobes.Histologically, shedding of the ciliated bronchial mucosal cells was prominent and this is attributed to a transudation of oedema fluid from the submucosa. Areas of regeneration of the mucosa, with the presence of simple stratified epithelium, were seen frequently. The loss of the ciliated respiratory epithelium and the transudation of oedema fluid into the bronchial lumen, with interference with the action of the remaining ciliated cells, are considered to be the essential factors in the failure of clearance of the bronchial secretions in asthma. It is postulated that bronchospasm plays little or no part in the shedding of the bronchial mucosa or in the pathogenesis of the asthmatic attack.

Fibrous bands have been described in the elastic (conducting) pulmonary arteries in 38 cases at necropsy, which represents a necropsy incidence of 14.4%. The fibrous bands are considered to represent one of the end results of episodes of pulmonary embolism. The formation of the bands is described and their significance is discussed in relation to their haemodynamic effects. Most of these bands are the result of clinically silent emboli.