Benign familial polycythaemia.

An English family suffering from thalassaemia minor is described. Three generations are affected, and all the affected members had a considerably raised red cell count in the presence of slight or moderate anaemia, obviously abnormal peripheral films, and only slightly reduced M.C.H.C. values; and each had a moderately raised haemoglobin A(2) level, though foetal haemoglobin levels were normal. The presentation of a family with erythrocytosis recalls the condition described in the older literature as benign familial polycythaemia which was, in some cases at least, thalassaemia minor. It is suggested that the presence of a raised red cell count is a more reliable distinguishing feature than the presence of target cells, or the serum iron level, in thalassaemia minor.

Practolol therapy associated with a systemic lupus erythematosus-like syndrome and an inhibitor to factor XIII.

A patient is described who had an inhibitor to coagulation factor XIII associated with serum autoantibodies to certain tissues. The relationship of these abnormal findings to practolol therapy suggests that this was practolol-induced lupus erythematosus. Further investigations delineating the site of action of the inhibitor to factor XIII are reported.

Comparison of liquid and dried sodium citrate as the anticoagulant for Thrombotest and prothrombin time estimations.

Samples which are taken for the Quick one-stage prothrombin time estimation for the control of patients receiving oral anticoagulant treatment are by convention taken into liquid sodium citrate anticoagulant. Dried sodium citrate has been rejected on the grounds that excessive haemolysis causes activation of clotting factors and therefore falsely short clotting times. Tests were performed with both liquid and dried sodium citrate as an anticoagulant for prothrombin time and Thrombotest. No clinically significant difference between the values given by the two anticoagulants was observed.

Comparative studies of a new commercial kit for the estimation of vitamin B12 in serum.

A commercial kit method (Technia Diagnostics) for the estimation of serum vitamin B12 claiming certain practical advantages was examined. Analytical and clinical performance were compared with a non-commercial radioisotope B12 method, previously compared to other commercial radioisotope B12 methods. The kit's analytical performance in our hands was satisfactory, although the within-batch precision and recovery of added cyanocobalamin were disappointing. Clinical performance was comparable with the non-commercial B12 method. Establishment of suitable reference ranges as a prerequisite to diagnostic use is apparent.

An evaluation of commercial radioisotope methods for the determination of folate and vitamin B12.

Five commercial kits for the determination of folate and six kits for the determination of vitamin B12 were investigated. Their performance has been compared with microbiological methods for the two vitamins and with a non-commercial radioisotopic method for B12. The results show the importance of the determination of the reference range for an individual laboratory for each method. The precision of the kits varied appreciably, as did their performance using specimens from patients with different haematological disorders. In particular, certain kits failed to detect all patients with pernicious anaemia. The relative accuracy of the kits was assessed. Various factors which should be taken into account in the final selection of a satisfactory kit are discussed.

Acute intravascular hemolysis with minimal renal impairment in Clostridium perfringens infection.

We report here a case of post-abortal clostridium prefringens infection in which there was severe intravascular hemolysis with black urine, but only minor abnormalities of the clotting mechanism and mild renal failure. The patient recovered following supportive therapy only.

Felty's syndrome.

An unusual case is presented in which a patient complained of oral ulceration and soreness of the mouth and throat. The results of clinical and laboratory investigations are reported and it was concluded that these oral symptoms were associated with Felty's Syndrome. After treatment of oral infection and a dental clearance the patient was virtually symptom-free for five months. The patient had a relapse and was admitted to hospital for treatment of overwhelming infection. Splenectomy was performed without sustained benefit and the patient died six weeks later.

Evaluation of the Hematrak differential leucocyte counter.

The main objectives of the evaluation were to: (1) assess accuracy and precision of cell recognition, (2) establish 'reference ranges' and compare with existing ranges, (3) assess machine reliability and suitability for normal working patterns. The accuracy and precision of the instrument were found to be acceptable, within the limits imposed by counting 100 cells in a wedge smear. Reference ranges compared well with established ranges with the exception of monocytes and eosinophils. the instrument was initially evaluated over a 12-week period and has been in routine use for 18 months durng which time it has been found to be very reliable. It has fitted in with the laboratory working patterns without causing any changes in work flow.

Thymoma associated with pure red cell aplasia, immunoglobulin deficiency and an inhibitor of antigen-induced lymphocyte transformation.

A case of thymoma associated with pure red cell aplasia and hypogammaglobulinaemia is described in which the anaemia was of abrupt onset, following removal of the tumour. Tests of immunological function showed abnormalities of both humoral and cellular immunity. The patient was found to have a serum inhibitor of antigen-induced lymphocyte transformation which disappeared after immunosuppressive therapy at the same time that erythroblasts reappeared in the marrow. It is suggested that the triad of thymoma, pure red cell aplasia and immunoglobulin deficiency are manifestations of 'pluripotent' stem cell failure; in this case the inhibitor of lymphocyte transformation may have been related to the factor which also inhibited red cell maturation.

Microcomputer data handling for the Phoenix system.

A modified Phoenix data processing system has been introduced into the laboratories at the Manchester Royal Infirmary. Specifications for the design and installation of microcomputers to link automated instruments to this host computer are described. The operation and data manipulation facilities of the microcomputer are included. It is concluded that these devices aid the management of data within the department and improve the quality of service.

Active immunotherapy used alone for maintenance of patients with acute myeloid leukaemia.

A total of 32 patients suffering from acute myeloid leukaemia were initially treated with daunorubicin and cytosine arabinoside, and eight who achieved full remission were given a brief cytoreduction course of cyclophosphamide and thioguanine. Of these eight patients seven were then actively immunized with 10 irradiated allogeneic acute myeloid leukaemia cells and B.C.G. at weekly intervals. Six of these patients have survived in apparent good health for more than one year. Bone marrow changes suggestive of relapse were used as an indication for further short courses of chemotherapy, and except on single occasions in two different patients clinical relapse has been prevented. The average duration of first (bone marrow) remission appears to be comparable with the best achieved in trials using regular chemotherapy for maintenance, though criteria for determining relapse may be different. The rate of reinduction of remissions (bone marrow) in this series was high, with a subsequent increase in overall survival time. Possible explanations for the high rate of reinduction include, firstly, the effects of active immunization with specific leukaemia antigen; secondly, non-specific adjuvant effect; thirdly, avoidance of drug resistance; and, fourthly, early diagnosis of relapse by frequent bone marrow examinations.

A proposal for further standardization of red blood cell glucose 6-phosphate dehydrogenase determinations.

A number of factors were identified which influence the determination of red blood cell glucose 6-phosphate dehydrogenase (G6PD). White blood cells were effectively removed from whole blood by filtration, resulting in a mean reduction of G6PD activity of greater than 1.0 U/g Hb. Optimal enzyme activity was found using haemolysates with a Hb concentration in the range 0.4-1.2 g/dl. At a constant temperature of 30 degrees C, maximum linear rate of activity was achieved between the 10th and 20th min after initiation of the reaction. As a result of these findings, modifications to standardize the assay system were introduced. The new method exhibits excellent precision (CV less than 2.0%) with normal samples, and 95% reference ranges of 7.00-11.15 U/g Hb for adult females and 7.05-10.75 U/g Hb for adult males.

Bone marrow culture studies in refractory cytopenia and 'smouldering leukaemia'.

As an adjunct to conventional haematological and cytogenetic data, 22 cases of refractory cytopenia, and five with chronic myelomonocytic leukaemia, (CMML) were studied by bone marrow culture. Cultures from II such patients without an excess of marrow myeloblasts usually showed low, or undetectable, numbers of cells capable of giving rise to colonies of granulocytes and/or macrophages (CFUc) but near-normal numbers of cluster-forming cells and cells capable of forming erythroid colonies (CFUE). Those with similar blood pictures, but in whom the marrow contained a slight excess of myeloblasts (II cases), showed a more profound defect in growth patterns: low or undetectable numbers of CFUC, clusters and CFUE, results similar to those found in acute myeloblastic leukaemia, into which three of this group evolved. The patients with CMML gave comparatively normal CFUC, cluster and CFUE growth patterns.

An abnormal fibrinogen with delayed fibrinopeptide A release.

Investigation of the family of a patient presenting with haematuria revealed seven cases in three generations showing a prolonged thrombin clotting time. A dysfibrinogenaemia was confirmed when purified fibrinogen from an affected member of the family was shown to also exhibit a prolonged thrombin clotting time. No molecular abnormality could be demonstrated using electrophoretic and immunological techniques. However, using a specific radioimmunoassay to fibrinopeptide A a major defect has been localized to a delay in the rate of release of this peptide by thrombin when the abnormal fibrinogen is converted to fibrin. This case of dysfibrinogenaemia has been tentatively designated fibrinogen Manchester.

Immunotherapy alone vs no maintenance treatment in acute myelogenous leukaemia.

Forty-one adult patients with acute myelogenous leukaemia entered remission induced by daunorubicin and cytosine arabinoside, and subsequently received 6 weeks' consolidation therapy with cyclophosphamide plus 6-thioguanine. They were then randomized to either immunotherapy consisting of intradermal BCG plus allogeneic cells or to "no maintenance". Patients receiving immunotherapy had significantly longer remission (P = 0.039) and survival from remission (P = 0.044) as assessed by the log-rank test. The median duration of first remission for 21 patients receiving immunotherapy was 35.14 weeks, compared with 19.71 weeks for 20 patients on no maintenance, and the median survival from remission was doubled in patients receiving immunotherapy. The value of adequate consolidation chemotherapy is confirmed by the comparatively long first remissions in both groups compared with our previous trials, whilst avoidance of maintenance chemotherapy possibly allowed frequent second remissions and similar post-relapse survival in patients from both treatment arms.

Active immunotherapy in acute myelogenous leukaemia and the induction of second and subsequent remissions.

One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.

Chronic myelomonocytic leukaemia.

The natural history and haematological features of 18 patients with a chronic form of myelomonocytic leukaemia are described. The majority were elderly and, in this series, females predominated. Haematological prodomata, such as unexplained monocytosis, leucopenia, or thrombocytopenia were common, and the clinical onset was insidious. Splenomegaly was variable but tended to increase as the disease progressed. Anaemia was usually less than in the acute disease, unless compounded by iron deficiency. The blood film typically showed a mixed monocytosis and granulocytosis, cells in both lines showing abnormalities. 'Paramyeloid' cells, appearing in Romanowsky stained films intermediate between myelocytes and monocytes, were characteristic, although cytochemical and electron microscopical analysis suggests that these cells may be allotted to one or other cell line. The marrow aspirate was characteristically hypercellular, showed granulocytic hyperplasia, and, in contrast to the well-differentiated blood picture, the proportion of poorly differentiated cells, including blasts, was high. Serum lysozyme levels were usually raised. Five of the 18 cases survived more than 5 years, while 10 lived 2 years or longer. The morphological and clinical features form part of a spectrum including acute myelomonocytic leukaemia, into which several of the patients transformed. Recognition of the syndrome is important because the patients are probably best managed without intensive chemotherapy.

Streptokinase in acute myocardial infarction: a controlled multicentre study in the United Kingdom.

In a multicentre trial of streptokinase in acute myocardial infarction 302 patients received an intravenous infusion of 2 500 000 IU of streptokinase over 24 hours, while 293 patients served as controls. Neither group received anticoagulants unless indicated by thromboembolic complications. No significant difference in mortality was evident during inpatient treatment nor at six-week or six-month follow-up. The inpatient death rate was 12-6% in the streptokinase group and 13-7% among controls. There was no significant difference in the peak levels or pattern of enzyme increase. The incidence of cardiac failure and reinfarction was similar in the two groups, but major arrhythmias were less common in those on streptokinase (P less than 0-05). In the streptokinase group there were 36 minor and six more serious haemorrhagic complications. Gastrointestinal haemorrhage may have contributed to the death of one patient in each group. There were 18 thromboembolic complications in the streptokinase group and 38 among the controls. Pathological examination of the hearts of 25 patients who had taken streptokinase and 24 controls showed no striking differences between the groups, but haemorrhagic infarcts were found in three patients who had received streptokinase. An infusion of streptokinase within 24 hours of the onset of acute myocardial infarction does not significantly affect the mortality or course of the illness up to six months.