Sickle cell disease and nitrous oxide-induced neuropathy.

We report three cases of peripheral neuropathy in patients with sickle cell disease. All had a history of frequent painful crises and regular attendance at our Accident and Emergency department where nitrous oxide analgesia was administered for prolonged periods. All three patients (one male and two females) presented with difficulty in walking associated with paraesthesiae, and neurological examination revealed signs compatible with a peripheral sensorimotor neuropathy, later confirmed by nerve conduction studies. Serum vitamin B12 levels were mildly reduced in two patients and very low in one patient (< 10 ng/l). Haemoglobin levels in all the patients were unchanged compared with their steady-state levels but one had developed a macrocytosis (103 fl). Schilling tests were normal in two patients, and two patients had negative gastric parietal antibodies. All three patients were given intramuscular vitamin B12 in addition to avoiding further exposure to nitrous oxide, and their neurological symptoms improved completely. As nitrous oxide is known to cause a neuropathy similar to that seen in pernicious anaemia, we postulate that nitrous oxide analgesia combined with low B12 levels was the cause of the marked neuropathy in these patients. As a result of our observations and the probable association, we now do not use nitrous oxide analgesia in the management of patients with sickle cell disease.

Coexistent hairy cell leukaemia and chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) and hairy cell leukaemia (HCL) are chronic B-cell lymphoproliferative disorders (B-LPDs) with distinct clinical, morphological and immunocytochemical features. Transformation of CLL into other B-LPDs (prolymphocytic leukaemia (PLL) and large cell lymphoma) is a well recognised phenomenon. One previous report has suggested that HCL may also arise by clonal evolution from CLL. We report the case of a 75 year old man in whom a diagnosis of coexisting HCL was made seventeen years after an initial diagnosis of CLL. Immunoglobulin heavy chain rearrangement studies suggest that the two B-LPDs developed independently. A steady increase in the bone marrow HCL component at the expense of the CLL component was observed with time, suggesting that HCL may have a growth advantage over CLL.

The venous closing pressure in central retinal vein obstruction.

OBJECTIVE: To assess the rate of change in the central retinal venous closing pressure in central retinal vein obstruction over time, and its relationship to visual acuity improvement and the development of rubeosis iridis. METHODS: Fifty patients presenting with central retinal vein obstruction of less than three months' duration, between the ages of 40 and 80 years, were reviewed prospectively. The central retinal venous closing pressure was measured by digital ocular compression. Patients were discharged from the study after the six-month visit. RESULTS: All patients had elevated venous closing pressure at presentation, whereas at six months only 24 patients had persistent elevation. Of 16 patients with lowering of the venous closing pressure within four months of onset of central retinal vein obstruction, 11 (69%) had two or more lines of visual acuity improvement. Only two of 10 patients (20%) developing lowering of the venous closing pressure thereafter had visual improvement. No patient developed rubeosis iridis after the venous closing pressure lowered. CONCLUSION: The central retinal venous closing pressure is raised in central retinal vein obstruction to about central retinal arterial diastolic pressure, and is its pathognomonic sign. This sign is easily elicited via digital pressure on the eyelid, and has prognostic significance for visual acuity improvement and the development of rubeosis iridis.

Heterogeneous X-ray survival characteristics of lymphocytes in prolymphocytic leukaemia: mathematical analysis distinguishing delayed cell death and true radioresistance.

The survival of non-dividing (G0) leukaemic lymphocytes in culture is generally too short for their radiosensitivity to be quantitatively assessed, since lethally X-irradiated cells may show a long delay before manifestations of cell death ("interphase death") are seen. Counts of surviving cells will therefore include both lethally-hit cells (apparent survivors), and real survivors which have not been lethally hit. Death rates of irradiated leukaemic and normal cells show great variation between individuals, so that comparisons of radiosensitivity between different cell populations based on surviving cell counts at a single time-point are invalid. In this study the supposed radioresistance of prolymphocytic leukaemia lymphocytes was examined in 6 patients with B-cell disease. Survival curves were plotted from serial observations made over several days after graded X-irradiation (0-1000 cGy). We attempted to interpret these radiation responses in terms of their dose dependence (intrinsic radiosensitivity) and time dependence (cell death rate) characteristics using the best-fitting of four mathematical models, all based on classical "single-hit" target theory. The apparent radioresistance shown in 4 cases could be explained by very slow death rates (T1/2 values 55-205 h) of cells proving otherwise radiosensitive (D37 values 38-123 cGy). Genuine radioresistance was found in only 1 case (actual D37 value above 2000 cGy). By ignoring delayed cell death in clinical assessments, pathological lymphocytes could be mistakenly categorised as resistant to elimination by radiotherapy.

Waldenström's macroglobulinaemia terminating in acute myeloid leukaemia: report of a case and review of the literature.

We report on a patient originally diagnosed as having monoclonal gammopathy of undetermined significance (MGUS) who progressed to develop Waldenström's macroglobulinaemia (WM) after 3 years. Four years later he developed chronic myelomonocytic leukaemia (CMMoL) which terminated in acute myeloid leukaemia (AML) after another year. We also review published reports of similar cases.

Clinical spectrum of autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia.

Autoimmune haemolytic anaemia (AIHA) is a frequent complication of chronic lymphocytic leukaemia (CLL). The course of AIHA in CLL is quite variable and unpredictable. We report 9 patients who showed three distinct clinical patterns. Three patients had a single episode of AIHA which responded rapidly to oral prednisolone. Three others had a relapsing course often associated with a rising lymphocyte count which responded to a combination of prednisolone and cytotoxic drugs. The remaining three patients showed very little response to either form of treatment and continued to have haemolytic anaemia for the remainder of their lives. Development of AIHA did not appear to be associated with any particular stage of the disease and only patients with the third type of AIHA seemed to have a short survival.

The value of the bone marrow plasma cell cytoplasmic light chain ratio in differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance.

We compared the plasma cell light chain ratios in the bone marrows of 13 patients with multiple myeloma (MM), with those of 13 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean light chain ratio in favour of the paraprotein isotype in the myeloma group was 51.83 (95% confidence limits (CL) 29.52-74.14), while in the MGUS group it was 5.30 (CL 2.07-8.52). The difference between the MGUS and MM groups was significant (p = 0.0005). Neither the bone marrow plasma cell count nor the paraprotein level were significantly correlated with the light chain ratio in either of these two groups. We found a cut-off ratio of 8 to be the most useful in differentiating between myeloma and MGUS. Only one patient with myeloma had a ratio below 8, and one MGUS patient had a ratio above this cut-off point. We conclude that determination of the bone marrow plasma cell light chain ratio is a simple and useful test in differentiating between myeloma and MGUS in difficult cases.

Plasmapheresis for severe, unremitting, chronic urticaria.

Histamine-releasing autoantibodies have been identified in chronic idiopathic urticaria. 8 patients with severe disease and histamine-releasing activity in their sera underwent plasmapheresis. Symptoms were abolished for 2 months in 1 patient and for 3 weeks in another, 2 showed almost complete resolution of symptoms, 2 had temporary relief, and the other 2 showed little change. Further investigation in 4 of the patients showed significantly reduced skin-test responses to fresh post-exchange autologous sera after plasmapheresis compared with stored pre-exchange sera, but the response to intradermal histamine remained unchanged. Blood cellular histamine increased as in-vitro serum histamine-releasing activity fell after plasmapheresis. These results favour a pathogenetic role for histamine-releasing autoantibodies in patients with chronic urticaria.

Autologous blood transfusion today.

Autologous blood transfusion--the transfusion to a patient of his or her own blood--is increasingly being recognised as a useful adjunct to traditional transfusion practice. The reasons include fears of disease transmission, the potential adverse effects on the recipient's immune system of transfused donor blood, and logistical factors. The three main techniques of autologous transfusion are: (i) pre-deposit, in which patients donate blood over a period of time in preparation for elective surgery; (ii) pre-operative isovolaemic haemodilution, in which blood is removed immediately before surgery and volume replacement is given, the blood being reinfused post-operatively; and (iii) salvage transfusion--the collection of blood shed at surgery or in similar circumstances, which is reinfused immediately or after concentration and purification. All three techniques can help to improve the safety of transfusion and economise on scarce supplies of donor blood.

The haemodynamic responses to venesection and the effects of cardiovascular disease.

The haemodynamic effects of the venesection of one unit (450 ml) of blood over 9 min were measured using non-invasive techniques, in 14 healthy controls and 18 patients with coronary heart disease or hypertension. Venesection was associated with significant reductions in supine and standing systolic and diastolic blood pressure, stroke volume index and cardiac index, and increases in standing heart rate, in both patient groups. No significant differences were observed between the responses of subjects with and without cardiovascular disease. The authors conclude that, in contrast to established teaching, blood loss can be detected in its early stages by careful haemodynamic monitoring and that venesection can be performed safely without volume replacement in patients with stable cardiovascular disease.

An in-vitro direct chemiluminescence assay for assessment of platelet-bound antibody in thrombocytopenic patients.

A direct chemiluminescence test (CLT) employing autologous monocytes and granulocytes was used to assay platelet-bound antibody in comparison to the direct platelet suspension immunofluorescence test (PSIFT) in 50 patients. Twenty-six of the 30 immune thrombocytopenic purpura (ITP) patients, including all 21 chronic ITP patients with platelet counts below 100 x 10(9)/l, showed positive results with at least one type of phagocytic cell; so did seven of the eight patients with other presumed autoimmune thrombocytopenias, and three out of 12 patients with thrombocytopenia associated with non-immune disorders. This test appears potentially valuable in the clinical diagnosis of immune thrombocytopenias.

Autologous blood transfusion.

Autologous blood transfusion--transfusion to the patient of his or her own blood--is of increasing importance in transfusion practice. There are three main techniques: pre-deposit, in which patients donate blood over a period of time in preparation for elective surgery; preoperative isovolaemic haemodilution, in which blood is removed in theatre immediately preoperatively and volume replacement is given, the blood being reinfused postoperatively; and salvage transfusion - the harvesting of blood shed at surgery or in similar circumstances, which is reinfused immediately or after concentration and purification. All these techniques can play a part in rendering transfusion safer and in economising on scarce supplies of donor blood.

Role of splenectomy as a salvage procedure in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura is a rare but serious haematological disease for which first-line therapy is medical, but not always successful. The role of splenectomy in the management of such patients is unclear. This paper reports three patients with the condition who went into remission following splenectomy after other forms of therapy had failed. Because thrombotic thrombocytopenic purpura is nearly always fatal if a remission is not obtained, splenectomy should be considered in patients who prove to be resistant to medical therapy.

Simplified quantitative estimation in vitro of lymphocyte radiosensitivity applied to patients with chronic lymphocytic leukaemia.

Lymphocyte survival changes observed at 1, 2 and 3 days as responses to 3 doses of ionising radiation in vitro (40, 100, and 500 cGy) are analysed by computer according to a simple (single cell population) mathematical model. Intrinsic radiosensitivity, the susceptibility to lethal injury, which is expressed as the D37 value (the radiation dose permitting 37% survival), is estimated separately from the kinetics of subsequent death of lethally-irradiated cells (expressed as their half-life, or t1/2 value). Among the 35 patients with B-cell CLL studied (15 were never treated), both parameters varied widely and independently of one another. t1/2 ranged from 9-200 h and above, D37 from 14-500 cGy or above. Twenty-three patients were deemed 'radiosensitive' (D37 below 110 cGy). D37 level did not correlate with treatment status, mode of treatment, clinical staging (Rai) or lymphocyte count. With some exceptions, D37 remained relatively constant for individual patients with increasing duration of disease or alterations in treatment status. The assay method may prove useful as an aid in predicting response to low-dose splenic irradiation (SI) in CLL.

Intravenous and oral demethoxydaunorubicin (NSC 256-439) in the treatment of acute leukemia and lymphoma: a pilot study.

Demethoxydaunorubicin (DMDR), a new anthracycline available both for intravenous and oral administration, was given in 14 cases of leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) replacing either daunorubicin (DNR) or doxorubicin (DOX) in conventional chemotherapy regimes. In acute leukaemia (6 myeloblastic and 1 common lymphoblastic) there were 5 complete (CR) and 2 partial (PR) remissions; one patient, previously brought into remission with a regime including i.v. DMDR was thereafter maintained in CR with oral DMDR. Among the patients treated with the oral DMDR, 2 NHL cases were treated; 1 patient had a sustained remission of 12 months so far, with DMDR alone; another patient had a CR with a combined regime. In MM, one patient with very advanced disease treated with i.v. DMDR/CHOP did not respond, but three cases treated with oral DMDR plus other drugs showed a partial remission. Toxic effects were limited to brief episodes of nausea and vomiting in a few i.v. treated patients; a prolonged bone marrow depression was observed in one case only. No cardiotoxic effect was recorded.