Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases.

Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL.

Leucocyte numbers and quality: their effect on viscosity.

Leucocyte suspension viscosity was measured using cells from a number of leukaemias. Samples from individuals with acute myelomonocytic and myeloid leukaemias, and chronic myelogenous and chronic lymphatic leukaemias were examined for their viscosity and flow properties. Leucocytes were suspended in native plasma and the effect of variable leucocyte numbers in the ranges seen in some leukaemias (100-600 x 10(9)/l) examined at different shear stresses. The effect of MCV was also determined in relation to viscosity. The results showed an increasing order of viscosity from the leucocytes of chronic lymphatic leukaemia through chronic myelogenous and acute myeloid leukaemia to the acute myelomonocytic variety. This bears some relation to the mean corpuscular volume, but confirms the fact that at high numbers of cells, patients with acute myelomonocytic, and to a lesser extent the myeloid leukaemias, are at considerable risk of blood hyperviscosity.

Factor X-activating procoagulant in normal and malignant breast tissue.

Factor X-activating activity (FXAA) was determined by a chromogenic assay in normal and malignant breast tissue. FXAA was found in all tissue (n = 38) irrespective of pathology, and the activity of normal tissue was similar to that of tumours. FXAA correlated with tissue hemoglobin in normal breast (p less than 0.02) but not in tumours. FXAA was markedly reduced by aluminium hydroxide, barium citrate, anti-human factor VII, DFP, PMSF and phospholipase C, but was unaffected by iodoacetamide and mercuric chloride. It is concluded that FXAA is a serine protease with the properties of a tissue factor-factor VII complex. FXAA occurs in normal and malignant breast tissue, although the 'normal' activity may be an artefact of the homogenization process.

Procoagulant activity in whole blood from patients with breast and colorectal cancer.

Whole blood procoagulant activity was determined by measuring the endotoxin-induced shortening of the celite-activated whole blood recalcification time in patients with breast cancer (n = 29), colorectal cancer (n = 18), benign breast disease (n = 26), benign colorectal disease (n = 10), normal volunteers (n = 17) and surgical in-patients with non-malignant and non-inflammatory conditions (n = 18). Using this method, patients with breast and colorectal cancer produced significantly more procoagulant activity than normal controls (P less than 0.001), surgical in-patients (P less than 0.005) and patients with benign breast (P less than 0.001) and benign colorectal (P = 0.05) disease respectively. The difference between subjects classified as 'cancer' or 'non-cancer' was highly significant (P less than 0.0001). There were no significant differences in total white cell or absolute monocyte counts between subject groups, and in individual patients, there was no correlation between these parameters and the procoagulant activity. It is concluded that the activated whole blood recalcification time is a more reproducible way of measuring whole blood procoagulant activity than the original technique, and that using this method, patients with cancer show higher procoagulant activity than corresponding benign controls.

Evaluation and comparison of neutrophil bipolar shape formation with a migration assay.

The neutrophil shape change response to a chemotactic formylpeptide was assessed. Neutrophil bipolar shape formation (BSF) was also simultaneously assessed with a Boyden chamber-based neutrophil migration assay. Both assays were precise and relatively reproducible; the average coefficient of variation for the BSF assay was 9.6% and 9.2% for the migration assay. In a blind study the BSF assay showed 100% sensitivity at detecting subjects with known abnormal neutrophil migration. Unlike the migration assay, the BSF assay does not require isolated neutrophils, reducing possible cell activation and monitoring the cell response under more physiological conditions. Small blood samples--1 ml or less compared with 20-40 ml for the migration assay--are used, and the method is technically simple. Results are available within 40 minutes, and routine (EDTA) blood samples are used. It is concluded that the BSF assay is a suitable motility screening test for both the clinical and pharmacological examination of the movement of polymorphonuclear leucocytes.

Management of Raynaud's phenomenon. Focus on newer treatments.

Current thinking on the general approaches to handling patients with Raynaud's disease is briefly described, and the principles of management discussed. The various categories of drug treatment available - vasodilators, especially those active on the smallest blood vessels, drugs acting on endothelium and platelets and their products, rheologically active drugs and some whose action it is difficult to classify - are mentioned. By far the most widely tested drugs in this field are the dihydropyridine-like slow calcium channel antagonists, of which nifedipine is probably the best known. Side effects are common and the optimal dosage and drug formulation are yet to be achieved. Serotonin antagonists (naftidrofuryl, ketanserin) look promising, although ketanserin is not generally available yet. Drugs active in the sympathetic control of vascular tone may well be best reserved for the most severe forms of Raynaud's, especially perhaps those associated with tissue loss in the secondary disease. Older vasodilators, such as glyceryl trinitrate (nitroglycerin) and some of the nicotinic acid derivatives, have not been studied of late but the transdermal applications of glyceryl trinitrate at least sound attractive. Drugs active in the cyclo-oxygenase systems, especially those with prostacyclin-like activity or thromboxane antagonists, are obviously promising; however, their unavailability in oral, sublingual or transdermal forms limits comment on them at present. Non-drug approaches such as biofeedback control of vascular responses may be interesting in a small number of patients, but the advice to 'keep warm' (and how to achieve this) is probably the most valuable suggestion that can be given to patients with Raynaud's disease.

Whole blood procoagulant activity in breast and colorectal cancer.

Whole blood procoagulant activity was determined by measuring the recalcification time of citrated blood, with and without the addition of bacterial endotoxin, in patients with breast cancer (n = 39), colorectal cancer (n = 20), benign breast disease (n = 15), benign colorectal disease (n = 11), normal volunteers (n = 15) and inpatients with non-malignant disease (n = 22). The median clotting times of those samples incubated with endotoxin were significantly shorter in the patients with breast and colorectal cancer compared with normal controls. Furthermore, significant differences between the median clotting times of stimulated and unstimulated samples within each subject group were observed only in the two cancer groups. There was no correlation between whole blood procoagulant activity and absolute monocyte counts, with histological staging or with plasma concentrations of plasma fibrinopeptide A. The results suggest that blood from patients with cancer is more sensitive to endotoxin stimulation than that from normal or benign controls, but that in its present form the technique cannot be used to distinguish between malignant and non-malignant disease.