Comparison of weal and flare responses to platelet activating factor (PAF) and histamine, and the ultrastructural effects of PAF in the skin of atopic and normal subjects.

Weal volume and flare area responses to intradermal platelet activating factor (PAF) and histamine, both in the presence and absence of the protein carrier, human serum albumin (HSA), were measured in the skin of normal subjects, atopics without dermatitis, and in the normal-appearing skin of patients with atopic dermatitis. The ultrastructural effects of intradermal PAF were also studied in the same groups of subjects. Weal and flare dose-responses to PAF were enhanced by the presence of human serum albumin, HSA itself producing a significantly greater mean weal response in each group than lyso-PAF (P < 0.01). However, comparison of normal subjects, atopics without dermatitis and patients with atopic dermatitis, showed the differences in dose-response effects of PAF and histamine on weal volume and flare area to be nonsignificant. The cellular response to PAF in normal subjects and atopics consisted predominantly of neutrophil extravasation; eosinophils were noted in the normal-appearing skin of atopics and patients with atopic dermatitis 30 min and 4 h after injection. At an ultrastructural level PAF induced opening of endothelial gaps and extravasation of neutrophils in each group.

Weathering nodules of the ear: a clinicopathological study.

Twenty-five cases of distinctive ear nodules on the helices of the ears in elderly males are presented. We believe the clinicopathological features of these lesions allow them to be defined as a distinct entity. They are probably more common than is currently recognized. Histologically, a typical nodule comprises a spur of fibrous tissue with a focus of cartilage metaplasia. While the pathogenesis of weathering nodules remains unclear, there is an association with age and chronic UV exposure.

Minocycline-induced discolouration of the sclerae.

We report two patients with minocycline-induced pigmentation of the sclerae. Cutaneous pigmentation is a well-recognized complication of minocycline therapy, but only five cases of pigmentation of the sclerae have been described previously. These five patients have a number of features in common with the two reported here. We propose that these patients represent the most severe end of the spectrum of minocycline-induced cutaneous changes. Patients should be warned about the possibility of the occurrence of pigmentary changes before starting therapy.

Subungual keratoacanthoma--a report of four cases and review of the literature.

Subungual keratoacanthoma is a rare benign neoplasm which most commonly occurs in middle-aged Caucasians. It usually presents as a painful, rapidly growing lesion of the terminal phalanx. Radiography consistently demonstrates a well-defined cup-shaped erosion of the underlying bone. Clinically, subungual keratoacanthoma must be distinguished from subungual squamous carcinoma. We report four further cases and discuss the literature.

Erythema elevatum diutinum associated with Wegener's granulomatosis and IgA paraproteinemia.

A 69-year-old man had erythema elevatum diutinum for several years before he developed IgA paraproteinemia and a limited form of Wegener's granulomatosis. This is the first report of an association between erythema elevatum diutinum and Wegener's granulomatosis. IgA paraproteinemia has been reported in association with erythema elevatum diutinum but not with Wegener's granulomatosis.

Pathology of the defunctioned rectum in ulcerative colitis.

Faecal stream diversion may induce inflammatory changes in the defunctioned segment of the large intestine. These changes are predominantly mucosal, although confusing histological features including granulomas may be present. The pathology of 15 defunctioned rectal stumps has been studied. All patients had previously undergone urgent total colectomy for ulcerative colitis and rectal stumps had been left in situ while they awaited pelvic ileal reservoir construction. All rectal stumps showed predominantly mucosal disease but there were additional features such as florid lymphoid follicular hyperplasia (12 cases), transmural inflammation (nine cases), granulomas (four cases), fissures (eight cases), and changes akin to ischaemia or to pseudomembraneous colitis (four cases). These changes may result from a combination of defunctioning and of active ulcerative proctitis. Some induce a histological appearance that may mimic Crohn's disease. Nevertheless review of all 15 colectomy specimens showed unequivocal ulcerative colitis and none of the patients has subsequently shown any clinical, radiological, or pathological evidence to support a diagnosis of Crohn's disease. Histology of the rectal stump in ulcerative colitis may lead to an erroneous diagnosis of Crohn's disease and the patient may subsequently be denied the advantage of a pelvic ileal reservoir.

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.

The microscopic features of inflammatory abdominal aortic aneurysms: discriminant analysis.

Up to 15% of abdominal aortic aneurysms are designated as inflammatory. They are characterized by marked fibrous thickening of the aneurysmal wall, with the fibrosis extending into the adjacent retroperitoneum. Thirty-five abdominal aortic aneurysms were studied, 15 inflammatory and 20 atherosclerotic. Of the inflammatory group, 10 were symptomatic and five asymptomatic. For each resection specimen, 59 microscopic features (variables) were scored semi-quantitatively. Discriminant function analysis showed that endarteritis obliterans, fibrosis around nerves or ganglia at the outer margin of mural fibrosis, and the thickness of the combined fibrotic media and adventitia gave a satisfactory high discrimination between atherosclerotic and inflammatory aneurysms. When these three variables are used together, a histological diagnosis of inflammatory aneurysm can be made with an expected accuracy in excess of 80%.

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.

Hydroxyapatite and urate crystal induced cytokine release by macrophages.

Destructive osteoarthritis is characterised by rapidly progressive joint destruction associated with intra-articular deposition of hydroxyapatite crystals. The possible role of such crystals in the pathogenesis of this condition was investigated by testing the ability of hydroxyapatite crystals to stimulate the production of bone resorbing activity from mouse peritoneal macrophages. Urate crystals were used for comparison. Culture supernatants were tested for bone resorbing activity using the mouse calvarial bone resorption assay, for interleukin 1 using a standard lymphocyte activation assay, and for prostaglandin E2 by radioimmunoassay. Culture supernatants from macrophages incubated with hydroxyapatite crystals contained dialysable bone resorbing activity, high concentrations of prostaglandin E2, but no interleukin 1 like activity. The production of the bone resorbing agent was prevented by culturing macrophages with hydroxyapatite crystals in the presence of indomethacin. By contrast, culture supernatants from macrophages incubated with urate crystals contained bone resorbing activity, which was only partly removed by dialysis, and interleukin 1 like activity. The latter was shown to be increased in culture supernatants from macrophages incubated with urate crystals in the presence of indomethacin, while production of bone resorbing activity was partially inhibited. It is considered that the bone resorbing activity liberated from macrophages stimulated by hydroxyapatite crystals can be explained by the presence of prostaglandin E2 alone, whereas the activity liberated by urate crystals is due to both prostaglandin E2 and interleukin 1.

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.

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.

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.

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.

Sialomucins at resection margin and likelihood of recurrence in colorectal carcinoma.

Oncogenic transformation of colonic epithelium is accompanied by changes in surface carbohydrate, notably an increased secretion of sialomucins at the expense of the normally predominant sulphomucins. In a multicentre prospective trial the correlation between the presence of sialomucins at the resection margin and the subsequent development of local recurrence was studied in 250 patients who had undergone "curative" resection for colorectal carcinoma with a mean follow up period of 14 months. Nineteen of 70 patients (27.1%) with a sialomucin predominant pattern at either resection margin developed local recurrence compared with 15 of 180 patients (8.3%) with a mixed or sulphomucin predominant pattern (p less than 0.01). Increased sialomucin staining at the resection margins was associated with reduced survival in these patients (p less than 0.01). At a mean of 14 months of follow up 153 patients (85%) were alive in the sulphomucin group and 53 patients (76%) were alive in the sialomucin group. Regression analysis predicted five year survivals of 32.8% and 18.9% for the sulphomucin and sialomucin groups respectively. Abnormal mucus production at the resection margin in patients treated for colorectal carcinoma appears to identify those with a higher risk of local recurrence and reduced survival.

A serological mediator in chronic idiopathic urticaria--a clinical, immunological and histological evaluation.

Seven of twelve autologous sera from patients with chronic idiopathic urticaria re-injected intradermally produced a weal at the site of injection. There was no response in 19 control subjects. Patients showing a positive response had a shorter duration of disease and shorter duration of spontaneous weals, and their urticaria was less likely to be exacerbated by pressure. There was some serological evidence of circulating immune complexes in both positive and negative responders to autologous serum, but only two showed complement abnormalities. When six of the serum-positive patients were re-tested after one year, five still showed a positive response with their original stored serum, but only two, whose disease remained active, were positive when challenged with freshly drawn serum, suggesting that a serum mediator is only present when the urticaria is active. A marked neutrophil infiltrate was seen within and around small dermal blood vessels at the injection site in the majority of urticaria patients but this appearance did not correlate with weal formation. In control subjects the cellular response was mild and mainly mononuclear.

Apatite associated destructive arthritis.

Twelve patients, 11 women and one man, aged 66-83, with a distinctive type of destructive arthropathy are described. The principal joints affected were the shoulders (ten) and knees (seven). Clinical features included pain on use, large cool effusions, instability and rapid progression. Radiographs showed attrition of bone and cartilage with a paucity of reparative changes. Synovial fluids were viscous, with low cell counts, and stained positively for the presence of apatite-containing particles. Extensive calcific material was seen in the synovium of the four patients biopsied, and on the radiographs in seven. Most patients had some associated or preceding joint disorder. The literature on similar cases is reviewed, and the possible role of crystals and other aetiological factors is discussed. It is suggested that a characteristic form of large-joint atrophy can occur in elderly patients at a number of joint sites and in several different clinical settings.