Distribution of leukemia, lymphoma, and allied disease in parts of Great Britain: analysis by administrative districts and simulations of adjacencies. Leukaemia Research Fund 1984 Data Collection Group.

An analysis is presented of the distribution of cases of leukemia and allied disorders occurring in 151 administrative districts from England, Wales, and Scotland during 1984. The age-adjusted rates for certain conditions present an unusual pattern highlighting excessively high and low rates in parts of the country, some of which share contiguous boundaries. In particular, high rates for non-Hodgkin's lymphoma are found in rural Yorkshire districts, whereas leukemias and primary polycythemias are much more common in the Midland districts.

Alpha-1-antitrypsin globules in the liver and PiM phenotype.

The finding is recorded of typical a1-antitrypsin globules, confirmed by immunofluorescence and immunoperoxidase methods, in the hepatocytes of a patient shown to have a normal serum antitrypsin level and normal phenotype (TiM) for a1-antitrypsin. The identification of such globules can no longer be regarded as conclusive evidence of an abnormal a1-antitrypsin phenotype.

Pathological evaluation of computed tomography images of lungs.

A method is described which allows the features seen in images generated during computed tomography (CT) of lungs previously removed at necropsy to be compared with those seen in corresponding thin sections made from the same lungs. After removal from the body, lungs were inflation-fixed using warm formalin vapour before being x-rayed and then scanned in the inflated state. Slices corresponding to the CT scan images were made and x-rayed. Paper mounted sections were then prepared from each slice. Using these methods pathological correlative studies can be used both to validate the interpretation of CT scans of lungs and to assess the sensitivity of this imaging technique.

Direct immunofluorescence of skin using formalin-fixed paraffin-embedded sections.

The technique of direct immunofluorescence has been applied to skin biopsy specimens fixed in formalin and embedded in paraffin wax. The results have been compared with those obtained by using snap-frozen biopsy specimens from the same patients. Trypsinisation of the dewaxed material allowed subsequent detection of immunoglobulins, complement, and fibrinogen. When compared to the fluorescence in the snap-frozen specimens, the staining in the paraffin sections was less bright and there was a higher rate of negatives. Even so, it was possible to establish the diagnosis in most cases of pemphigus, pemphigoid, and lupus erythematosus.

Colour perception in pathologists: the Farnsworth-Munsell 100-hue test.

The value of many histological stains depends on the ability of the observer to differentiate colour. This ability was assessed in 30 histopathologists and cytopathologists of varying experience using the Farnsworth-Munsell 100-hue test. As a group, the pathologists performed better than a reference population. Twenty eight subjects showed a wide ranging ability to differentiate colour: none was colour blind. Three of the 30 pathologists, however, fell below the twentieth centile for normal subjects and only one was aware of this deficiency! They may unknowingly misinterpret subtle stains. Two of these three had specific and major defects which could affect their ability to interpret a wide range of less subtle stains. Those with the poorest colour discrimination were not those with the least experience of microscopy. Pathologists should be apprised of the importance of their ability to discriminate colour, and that formal colour vision testing of prospective histopathologists may be appropriate.

Aural polyps as predictors of underlying cholesteatoma.

In a retrospective study of 96 patients 16 different histological features were examined in 100 aural polyps to see whether some or any could be used to predict the presence or absence of a cholesteatoma underlying the polyp. The patients were divided into those who had cholesteatoma and those who did not, so that discriminatory features were identified. These were combined to make an overall prediction of the probability of a cholesteatoma in the middle ear. The results showed that any polyp that (i) was composed of raw granulation tissue and (ii) contained keratin as flakes or masses had a 70-80% probability of being associated with an underlying cholesteatoma. In contrast, when a polyp (i) was composed of a fibrous core, (ii) had a covering epithelium, and (iii) contained glands and lymphoid aggregates, there was a 70-80% probability of cholesteatoma being absent. This scoring system can be used to help surgeons decide whether surgical exploration of the mastoid should be undertaken.

A new look at reticuloendothelial blockade.

The characteristics of so-called reticuloendothelial blockade have been reinvestigated in mice using organ uptake, rather than blood clearance, as the main method of assessment. Blockade was induced by using i.v. dextran sulphate. I.v. 51Cr-labelled sheep red blood cells were used as test particles. Although clearance of colloid from the bloodstream induced prolongation of reticuloendothelial clearance of a subsequent dose of test particles, this was solely due to depression of hepatic phagocytosis and the splenic and bone-marrow clearance remained unimpaired. Because of this highly selective action of i.v. blockading colloid, and because testing via the i.v. route can only provide information about macrophages which line blood channels, the expression reticuloendothelial blockade is entirely inappropriate to describe these phenomena. Unexpectedly, the effects could be quantitated using a wide range of doses of this test particle and saturating doses were not required.

Polyarteritis nodosa associated with acute cytomegalovirus infection.

A case of polyarteritis nodosa is described in which the onset of the disease was associated with acute infection by cytomegalovirus. Peripheral neuropathy was the predominant clinical feature, and death occurred 4 years after the onset. This is the first recorded case of polyarteritis in which cytomegalovirus is of possible aetiological significance.

Focal mesangial proliferative glomerulonephritis in the rat caused by habu snake venom. A morphologic study.

A new model of focal mesangial proliferative glomerulonephritis in the rat has been produced by intravenous habu snake venom. Glomerulonephritis developed in 70% of rats surviving the first 6 hours after venom administration. The earliest ultrastructural change (10 minutes after venom) was the presence of loose platelet aggregates and free granules in the capillary lumen and mesangium. This was followed by dissolution of the matrix and endothelial damage. Between 4 and 24 hours, a characteristic focal and segmental ballooned lesion of glomerular capillaries developed. In these lesions, from 3 days onwards a segmental mesangial proliferation occurred, which persisted until sacrifice at 21 days.

Fat and thromboembolism after total hip replacement.

Three patients who died after total hip replacement were subjected to a necropsy examination. The object of this was to determine whether there was any evidence of a relationship between fat emboli produced by the surgery and thrombotic complications. All three patients showed extensive fat embolisation in the lungs and antemortem thrombosis. In two of these the morphological relationship between these two phenomena was such that it seems likely that the fat emboli preceded and caused the thrombosis.

The mesangial cell in glomerulonephritis. I. Mechanisms of hypercellularity in experimental immune complex glomerulonephritis.

One-shot active immune complex glomerulonephritis was induced in rabbits by intravenous bovine serum albumin (250 mg. per kg.) and the mechanism of glomerular hypercellularity investigated. Most of the extra cells were mononuclear with few polymorphonuclear leukocytes. Fibrin was present in severe lesions. Glomerular mitoses were seen in normal kidneys but were more common in hypercellular glomeruli. This is direct evidence of local proliferation. Also, biopsies taken 1 hour after giving tritiated thymidine contained locally labeled cells. The mitotic rate and degree of local labeling both varied in proportion to the degree of hypercellularity. By electron microscopy both mesangial and endothelial cells were identified in mitosis. The majority of the mononuclear cells in the hypercellular glomeruli could not be identified by position or ultrastructure. Infiltration by nonglomerular cells was confirmed by the presence of macrophages, lymphocytes, and plasma cells.

Left ventricular apical thin point.

The wall thickness of the apex of the left ventricle has been measured at its thinnest point in 60 adult hearts at necropsy. This measured 2 mm or less in 97% of them and 1 mm or less in 67%.

Verrucous carcinoma of the larynx.

Verrucous carcinoma of the larynx is an uncommon but distinct variety of well differentiated squamous carcinoma and accounts for 1-2% of all laryngeal squamous carcinomata. Awareness of the condition both by clinician and histopathologist is essential otherwise the diagnosis may not be made. From a review of the literature and personal assessment of the cases presented here it would appear that local conservative endoscopic treatment with careful follow-up may be the treatment of choice for certain verrucous carcinomata. Such treatment may be either suction diathermy or cryosurgery or laser surgery. Anaplastic transformation has been said to occur following irradiation of these tumours, though this view is not held by all clinicians, some of whom recommend radiotherapy for selected cases.

Increased antibody production following depression of hepatic phagocytosis.

The influence of Kupffer cell blockade on the humoral immune response to suboptimal doses of intravenous sheep red blood cells has been measured in mice. Hepatic phagocytosis was suppressed using dextran sulphate. Direct (IgM) and indirect (IgG) plaque-forming cells were measured in spleens from treated and untreated mice at varying times after the antigen. The results show that after Kupffer cell blockade both IgM and IgG responses correspond to the responses seen after a 10-fold greater dose of cells in control animals. The implications of this are discussed.

Fatal outcome arising from use of a sutureless "corkscrew" epicardial pacing electrode inserted into apex of left ventricle.

A 59-year-old man is described in whom the insertion of an epicardial sutureless "corkscrew" electrode resulted in fatal ventricular perforation. Fatal myocardial perforation can occur with this electrode and the apex of the left ventricle should never be used as the site of insertion. Necropsy also showed that the transvenous right ventricular electrode, inserted one year previously, had penetrated a tricuspid leaflet. This could have accounted for the ensuing pacing failure.

Bone resorbing activity in synovial fluids in destructive osteoarthritis and rheumatoid arthritis.

The synovial fluids of patients with a destructive form of osteoarthritis (DOA) were shown to contain high levels of bone resorbing activity as judged by the ability of the fluid to stimulate the release of 45Ca from labelled cultured mouse calvariae. The activity was lost on extended storage of the synovial fluids and was dependent for its effect on cellular activity in bone. Bone resorbing activity was present in most synovial fluids from patients with DOA and rheumatoid arthritis (RA) but occurred at higher levels in the former. In contrast, interleukin 1 (IL1) activity, measured by the mouse thymocytes costimulation assay, was higher in RA than DOA synovial fluids. Little or no bone resorbing or IL1 activity was detected in synovial fluids from patients with pseudogout or non-destructive osteoarthritis. These results suggest that most DOA synovial fluids contain a bone resorbing factor other than IL1. It is considered that the factor may be produced by synovial cells stimulated by hydroxyapatite crystals.

Histological appearances of the long saphenous vein.

The long saphenous vein is frequently used as a graft in both coronary artery and femoro-distal bypass surgery. The histological changes which are seen after implantation into the arterial system have been well documented in the past, but little attention has been focused on the histological appearances of the donor long saphenous vein prior to grafting. In this study, samples of the long saphenous vein in excess of that required for bypass have been examined. In none of the veins did the histological appearances conform to the described normal. All showed evidence of intimal fibrosis which contained elastic tissue and enmeshed smooth muscle cells. The longitudinal and circular muscle layers showed evidence of muscle cell hypertrophy with increase in intervening connective tissue. Elsewhere, similar histological changes have been attributed to 'arterialization'. This study shows that many of the changes are present prior to grafting and may be important in graft failure.

Detection of latent virus mRNA in tissues using the polymerase chain reaction.

The polymerase chain reaction (PCR) has been adapted for use in gene expression studies. Using this technique, we have been able to specifically detect Herpes simplex virus gene expression in the amount of RNA equivalent to that present in a single mouse ganglion. We have also detected specific transcription of the ras oncogene in biopsies of hepatocellular carcinoma tissue. The single tube RNA PCR reaction should be readily adaptable for use as a rapid screening tool in virus diagnosis; it is capable of detecting several virus infections simultaneously using extremely small tissue biopsies.