Pseudotumour cerebri and paraproteinaemia.

We describe two cases of haematological malignancy, lymphoma and myeloma, presenting with pseudotumour cerebri. A haematological disorder should be considered in the differential diagnosis of the cause of pseudotumour cerebri, and the treatment of pseudotumour cerebri should be considered in the management of haematological disease, especially in avoiding irreversible visual deficit.

A unique case of three autografts for acute myelogenous leukaemia with subsequent long term survival in second remission.

We report here a patient with acute mycloid leukaemia who relapsed 20 months after undergoing a double autograft procedure in first remission. He was reinduced and subsequently underwent a third autologous bone marrow transplantation in second remission using bone marrow harvested in second remission and a Busulphan and Cyclophosphamide conditioning regimen. Although the engraftment was very slow, he has remained in second remission for 34+ months. This case demonstrates that durable disease-free survival can be attained by a second preparative therapy, even in second remission, for patients relapsed after autologous bone marrow transplantation.

Beta-thalassemia unlinked to the beta-globin gene in an English family.

An inherited hypochromic microcytic anemia transmitted in an autosomal manner has been observed in three generations of an English family. Affected members had the hallmarks of heterozygous beta-thalassemia, ie, elevated levels of hemoglobin A2 and imbalanced globin chain synthesis. However, despite extensive sequence analysis, no mutations could be found in or around the beta-globin genes of either the propositus or two other affected members from two different generations. Linkage analysis using restriction fragment length polymorphisms in the beta-globin gene cluster clearly showed that the gene responsible for the beta-thalassemia phenotype segregates independently of the beta-gene complex. Therefore, this condition represents a novel form of the disease.

Autonomic control of insulin secretion and the treatment of heart failure.

To investigate the role of the autonomic nervous system in controlling insulin secretion 13 normal subjects and 5 patients with heart failure underwent insulin secretion tests. Alpha-adrenergic stimulation and beta-receptor blockade significantly depressed the secretion of insulin in response to intravenous tolbutamide in normal subjects, while both alpha-blockade and beta-stimulation significantly increased the insulin secretion response in both normal subjects and patients in heart failure. Parasympathetic stimulation and blockade had no significant effect on the insulin secretion response. These findings suggest that drugs that block the alpha-adrenergic receptors or stimulate the beta-adrenergic receptors by their ability to counteract the insulin suppression resulting from increased sympathetic nervous activity may play a vital metabolic part in the deranged metabolism of the failing heart in addition to their direct haemodynamic benefits.

Hairy-cell leukemia with hybrid B-T features: a study with a panel of monoclonal antibodies.

The peripheral blood of three patients with otherwise typical hairy-cell leukemia (HCL), but with a substantial number of circulating cells expressing both light chain restricted surface immunoglobulin (SIg) and sheep erythrocyte (E) receptor, was studied with a panel of monoclonal antibodies. The presence of hybrid B-T surface features was confirmed and, although as in previous studies of E+SIg+ proliferations, the precise phenotypes varied at different times of study, E+ non-T SIg+ and E+T+SIg+ populations were at times present in all three patients together with typical B hairy-cell (HC) and phenotypically normal T-cell populations. In one patient an E-OKT11+SIg+ population was also observed. Extensive precautions were taken to exclude spurious explanations for these hybrid phenotypes. These results are discussed in relation to the recent demonstration that both HCs and normal B cells can express T-cell features after appropriate in vitro stimulation.

Campylobacter septic abortion.

We have reported a case of a septic abortion caused by Campylobacter fetus ssp jejuni. This organism is best known for producing diarrhea, but is now being linked with more serious diseases, including pregnancy wastage.

Clinical and hemodynamic results of mitral valve replacement with autologous fascia lata grafts. Studies in patients with competent prostheses.

Nine patients with severe mitral disease were studied before and six months after mitral valve replacement with a three-cusp stented prosthesis using fresh autologous fascia lata tissue. Only patients in whom there was no auscultatory and angiographic evidence of incompetence of the replaced valve were selected for restudy. All patients claimed a marked improvement in their exercise capacity after operation and there was a significant reduction in radiographic heart size. The cardiac output at rest and the response to exercise were both reduced before operation and were unchanged after valve replacement. The elevated pulmonary arterial and wedge pressures were significantly reduced after operation in all patients both at rest and during exercise, but in no instance were the postoperative exercise values within normal limits. Left ventricular end-diastolic pressure was within normal limits at rest and during exercise in all patients after valve replacement but the average pressure gradient across the fascia lata valve was 6+/-1 mm Hg at rest and 18+/-3 mm Hg during exercise. These findings indicate that altough replacement of the diseased mitral valve with a competent fascia lata prosthesis afforded substantial symptomatic relief, reduction of cardiac enlargement and a lowering of the pulmonary vascular pressures, this artificial valve offered a significant obstruction to left ventricular diastolic filling, particularly during exercise.

Comparison of adrenergic beta-blocking drugs in angina pectoris.

The symptomatic, electrocardiographic, and haemodynamic effects of two adrenergic beta-blocking drugs, oxprenolol and propranolol, have been compared in equipotent intravenous doses in six patients with uncomplicated angina pectoris during treadmill exercise. The method of comparison included double-blind assessment and analysis with placebo control and randomized serial comparison in each patient. Both drugs produced an equal amelioration in symptoms in most of the patients. This was closely correlated with improvement in the electrocardiographic changes and a significant reduction in the exercising heart rate and systemic arterial pressure. This method of double-blind combined subjective and objective assessment carries distinct advantages in the comparative assessment of drug treatments in angina pectoris.

Detection of the BCR-ABL gene by reverse transcription/polymerase chain reaction and fluorescence in situ hybridization in a patient with Philadelphia chromosome negative acute lymphoblastic leukaemia.

The Philadelphia (Ph) chromosome is detected in leukaemia cells in approximately 20% of adults with acute lymphoblastic leukaemia (ALL). When treated with chemotherapy alone, Ph-positive ALL has a poor prognosis, and patients may benefit from bone marrow transplantation in first remission. Here we report a patient with chromosomally normal bone marrow, in all 60 cells analysed, who was found to have the p210-type BCR-ABL chimaeric transcript by RT/PCR. Fluorescence in situ hybridization was labelled cosmid probes for BCR and ABL showed the presence of BCR-ABL juxtaposition on a normal chromosome 22 in leukaemia cell metaphases. We conclude that molecular and cytogenetic methods should be used in conjunction to detect the BCR-ABL gene rearrangement in ALL.

Abnormalities of T-cell subsets in patients with neutropenia and an excess of lymphocytes in the bone marrow.

Morphological, surface-marker and culture studies were performed in three patients who had in common neutropenia and an excess of lymphocytes in the bone marrow, but who differed from each other in certain regards such as age and peripheral lymphocyte numbers. All three patients had an increased proportion of E-rosetting cells bearing Fc receptors for IgG. These cells were shown to be T lymphocytes by staining with monoclonal anti-T-cell sera and their subset phenotype was established as OKT4- OKT8+; in addition, a variable proportion of the cells was Ia+. The functional significance of this expanded subpopulation of T cells was not clear, but it was shown that they did not inhibit colony formation in vitro.

T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia.

We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic "classic" T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed.

Detection of clonal immunoglobulin gene rearrangements in the peripheral blood progenitor cells of patients with multiple myeloma: the potential role of purging with CD34 positive selection.

Aims-To determine the extent of clonal cell contamination of peripheral blood progenitor cell (PBPC) collections in patients with multiple myeloma (MM) and to assess the purging efficacy of CD34 positive selection.Methods-PBPC collections from 29 patients with MM were analysed for the presence of clonal immunoglobulin heavy chain (IgH) gene rearrangements with a fluorescence based PCR technique. In addition, the PBPC from eight of the 29 patients were "purged" by selection of CD34 positive haematopoietic progenitors with an avidin-biotin immunoabsorption column (Ceprate). In each case the unmanipulated PBPC, CD34 positive and waste fractions were all assessed for the presence of clonal IgH rearrangements.Results-Clonal IgH rearrangements (identical with those demonstrated in diagnostic bone marrow samples) were demonstrated in 10 (35%) of 29 cases and seemed to be confined to those with significant residual bone marrow disease. Clonal rearrangements were evident in the PBPC of two of the eight patients who underwent CD34 selection; in both instances a "clonal purge" was seen as it was not possible to demonstrate the clonal rearrangement in the CD34 positive fraction. In four of the six remaining cases the normal polyclonal fingerprint could not be demonstrated in the CD34 positive fraction, which is consistent with a significant reduction in contaminating B cells.Conclusions-Clonal cells contaminate PBPC collections in a significant proportion of patients with MM and may be eliminated by CD34 positive selection.