Audit of bone marrow aspirates and trephine biopsies in multiple myeloma--a single centre study.

We compared 79 simultaneous marrow aspirates and trephine biopsies from multiple myeloma patients for sensitivity, concordance, quality and clinical relevance. A total of 60 examinations had been performed for initial diagnosis, i.e. in cases of suspected myeloma and 19 at follow-up. Of which, 45 (57%) of trephine biopsies were less than 1.6 cm before processing and 33 (42%) were crushed and/or fragmented. Overall, only 19/79 (24%) of trephine biopsy specimens were of at least 1.6 cm length prior to processing and not disrupted. On the other hand, 75% of aspirates were particulate and satisfactory. Mean time between receipt of a trephine biopsy specimen and issuance of a histopathological report was 9 days. Although 40% of trephine biopsies yielded information that could not be reliably obtained from a bone marrow aspirate such information was in all cases clinically irrelevant or obtainable by non-invasive means. In all cases where myeloma was detected in a trephine biopsy it was also detected in a simultaneous bone marrow aspirate, if particulate. However, there were four (5%) cases in which myeloma was detected in such aspirates but not in simultaneously taken trephine biopsies. In cases (n=19) where repeat aspirates/trephine biopsies were taken for surveillance, concordance was found between reported changes in plasma cell ratio. Our data failed to demonstrate any added benefit from routinely performing trephine biopsies after a particulate specimen had been aspirated for the diagnosis or surveillance of myeloma. Furthermore, they suggest that particulate aspirates may be at least as sensitive as trephine biopsies for detecting myeloma.

Pityocampal erucism in a British serviceman in Croatia--a case report.

We present a case of erucism (caterpillar dermatitis) in a British serviceman deployed in Croatia on Operation Resolute. The aetiology, clinical features and diagnosis of erucism are discussed. Erucism should be highlighted as an environmental hazard in future troop deployments to the Mediterranean area.

Scrotal ulceration during all-trans retinoic (ATRA) therapy for acute promyelocytic leukaemia.

We report the development of painful scrotal ulceration in two patients during treatment with all-trans-retinoic acid (ATRA) for acute promyelocytic leukaemia (APL). ATRA 45 mg/m2 was administered orally for 8 days prior to the addition of standard induction chemotherapy. Painful scrotal ulceration developed in both cases within 2 weeks of therapy (9 and 13 days) and responded slowly to drug withdrawal and systemic, or topical, corticosteroids. A total of 17 APL patients have been treated with ATRA at our institution during the last 10 years, giving an incidence of approximately 12%. The present report, together with a review of literature, suggests that scrotal ulceration is a specific adverse effect of ATRA therapy and that this complication may be more common than previously documented.

Autoimmune thrombocytopenia: a complication of fludarabine therapy in lymphoproliferative disorders.

We describe two cases of autoimmune thrombocytopenia precipitated by fludarabine therapy in patients with chronic lymphatic leukaemia. Both were treated with high dose steroids and initially responded with recovery of normal platelet counts. One patient developed recurrent autoimmune thrombocytopenia on two occasions following re-exposure to the drug when his disease had become refractory to all other treatments. A retrospective review of the case notes of 45 patients with lymphoproliferative disorders treated with fludarabine over the past 6 years indicated the development of autoimmune thrombocytopenia in 4.5% (two out of 45) and autoimmune haemolytic anaemia in 6.7% (three of the 45).

Fatal cold anti-i autoimmune haemolytic anaemia complicating hairy cell leukaemia.

Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder associated with pancytopenia, splenomegaly and the presence of typical hairy B lymphocytes in the bone marrow and/or peripheral blood. The most significant complication relates to opportunistic infections that arise as a consequence of neutropenia and monocytopenia. HCL is occasionally associated with systemic autoimmune disorders including polyarteritis nodosa and rheumatoid disease. Secondary autoimmune haemolytic anaemia (AIHA) appears to be rare. We report on two cases of HCL complicated by fatal cold anti-i AIHA. Fulminant haemolysis causing death is rare in cold AIHA and only a few individual cases have been reported, none having anti-i specificity.

Phase III efficacy study of interleukin-3 after autologous bone marrow transplantation in patients with malignant lymphoma.

We evaluated the efficacy of recombinant human interleukin-3 (rhIL-3) in reducing the number of platelet transfusions and major infections after autologous bone marrow transplantation (ABMT) in patients with malignant lymphoma. 198 patients with non-Hodgkin's lymphoma (NHL, n = 111) and Hodgkin's disease (HD, n = 87) were randomized to receive rhIL-3 10 microgram/kg/d (n = 130) or placebo (n = 68) for a maximum of 28 d after ABMT. Several well-known conditioning regimens were used. From day 1 after ABMT patients were treated with placebo or rhIL-3 at a dose of 10 microgram/kg/d by continuous i.v. infusion for 7 d and then by s.c. administration for 21 d or until platelet (50 x 109/l) and neutrophil (0.5 x 109/l) recovery had occurred. Treatment was completed in 54% of the patients in the rhIL-3 group versus 75% in the placebo group (P < 0.004). Adverse events were the main reason for premature discontinuation in the IL-3 group (23% IL-3 v 5% placebo). The median number of platelet transfusions was not significantly different between the IL-3 group and the placebo group (8.0 IL-3 v 6.0 placebo, P = 0.09). Platelet engraftment (>/= 20 x 109/l) was not significantly faster in the IL-3 group (28 d in the IL-3 and 27 d in the placebo group, P = 0.06) and the incidence of haemorrhagic complications was similar in both groups. In patients receiving the full intended dose of rhIL-3, platelet engraftment to >/= 20 x 109/l was delayed (P = 0.007). The median time to neutrophil engraftment was 23 d in the IL-3 and 25 d for the placebo group (P = 0.39). There was no difference in the incidence of major infections. We conclude that treatment with IL-3 has no clinical benefit in patients receiving ABMT for malignant lymphoma.

Aircrew lumbar supports: an update.

The numbers and types of aircraft flown by aircrew being issued with lumbar supports at the Aviation Medicine Training Centre (AMTC), Royal Air Force Henlow, has been examined for the year 1997. A total of 67 lumbar supports were issued, 46% to the Army, 37% to the RAF and 15% to the Royal Navy. Rotary wing aircraft constituted the majority of issues (73%) compared with fixed wing aircraft (27%); the Gazelle formed the highest component (34%), followed by the Lynx (20%) and the Sea King (14%). The Tornado and the Nimrod were in equal fourth place, each receiving 6% of the supports. The figures show the current distribution of aircraft types whose crews are being issued with lumbar supports and confirm the continued high incidence of backache among rotary wing aircrew.

Automated exchange transfusion for life-threatening plasmodium falciparum malaria--lessons relating to prophylaxis and treatment.

We report a case of traveller to Kenya who contracted severe plasmodium falciparum malaria complicated by disseminated intravascular coagulation and acute renal failure. She had taken no antimalarial prophylaxis in view of concerns in the media regarding the adverse effects of mefloquine. There was a protracted delay before the diagnosis of malaria was made. Clinical recovery occurred following treatment with intravenous quinine, haemofiltration and manual/automated red-cell exchange transfusions. Automated red-cell exchange transfusion resulted in a marked decrease in the parasitaemia, before a response to quinine therapy would have been anticipated, leading to a successful outcome thereafter. In conjunction with other groups we therefore feel that exchange transfusions should be considered in seriously ill patients with falciparum malaria, multiorgan complications and parasitaemias greater than 10%.

Efficacy of urate oxidase (uricozyme) in tumour lysis induced urate nephropathy.

Urate oxidase (uricozyme) is an enzyme of non-human origin capable of oxidizing human uric acid to allantoin, a highly soluble product at renal tubule pH. We report its efficacy in three patients with acute urate nephropathy due to tumour lysis in chronic lymphatic leukaemia and high grade lymphoma. Two patients had an additional obstructive nephropathy due to ureteric urate crystals. An intravenous infusion (100 units/kg in 50 ml saline over 30 min) was given for between two and five consecutive days. All patients showed a rapid fall in serum urate levels with associated diuresis, correction of metabolic disturbance and full resolution of uraemia within a week. The treatment was well tolerated and caused a rapid resolution of clinical symptoms in all cases. We review the literature relating to the use of this agent both in the treatment of hyperuricaemic acute renal failure and gouty arthritis.

An outbreak of rubella in British troops in Bosnia.

An outbreak of rubella in April 1996 involved four male British soldiers deployed to Bosnia-Herzegovina. All were helicopter ground crew who were members of the same unit and who periodically travelled to and worked at forward air refuelling stations in Bosnia. There was a potential for spread of the infection to adjacent British units, to troops of other nations in the peacekeeping force, and also to the local civilian population. The British force included 620 female personnel, some of whom may have been non-immune to rubella. One pregnant British servicewoman was repatriated to UK for her own protection. There was a potential health risk, including the possibility of congenital rubella syndrome, in the non-immune wives and partners of deployed male personnel, as a result of contact during the mid-tour home leave of the husbands or partners. The outbreak was monitored through a medical surveillance system known as ARRC 97, and was contained by prompt and rigorous control measures. This outbreak shows the importance of effective surveillance and of good microbiology laboratory support during military operations. The role of immunization against rubella during future military deployments is discussed.

Mental health problems on Operation Resolute (Bosnia).

Mental health problems have been studied in a total of 2201 consultations with British troops in a primary health care practice on Operation Resolute (Bosnia) from 1 January to 31 March 1996. About one in 40 (2.5%) of the consultations were for mental health problems; Post Traumatic Stress Disorder (PTSD), depressive disorder, and grief reaction were the most common disorders, followed by acute adjustment reaction and panic disorder. Most cases pre-dated deployment. The number of cases repatriated to the UK was 17, about 10% of the total number of patients repatriated from theatre in this period.

A study of primary health care at Divulje Barracks, Split on Operation Resolute (Bosnia).

A study of primary health care was undertaken at Divulje Barracks, Split, during Operation Resolute, 1996. A total of 1581 patients were seen during weeks 3 to 10 of the operation (day "13' to "70'). The number of consultations was greater for the first half of this period than for the second, and there were two early epidemics, one of respiratory disease and the other of enteric disease. Occupational and road traffic accident injuries were more common in the first 6 weeks and then declined with time.

Dermatological conditions in winter in primary health care on Operation Resolute (Bosnia).

The distribution of dermatological conditions has been studied in a total of 1822 consultations with British troops in a primary health care setting on Operation Resolute (Bosnia) between 1 January and 4 March 1996. Approximately one in eight (12%) of the consultations were for skin conditions; eczema was the most common complaint, but, taken as a whole, infections due to virus (excluding warts), fungus and bacteria made up 30%. The overall distribution of diseases was similar to that seen in British general practice.

A comparative analysis of radiological and surgical placement of central venous catheters.

PURPOSE: To compare the differences in practice and outcome of all radiologically and surgically placed central venous catheters retrospectively over a 2-year period simultaneously, at a single institution. METHODS: A total of 253 Hickman catheters were inserted in 209 patients; 120 were placed radiologically in 102 patients and 133 were placed surgically in 107 patients. The indication was chemotherapy in 76% of radiological and in 47% of surgical cases; the remainder were for total parenteral nutrition and venous access. RESULTS: There were 6 (4.5%) primary surgical failures and a further 17 (13%) surgical cases requiring multiple placement attempts. Pneumothorax occurred once (0.8%) surgically and four times (3.3%) radiologically. There were no radiological primary misplacements but there were five (3.7%) surgical ones. Catheter or central vein thrombosis occurred in four (3.3%) radiological and five (3.7%) surgical cases. The rate of infection per 1000 catheter-days was 1.9 in radiologically placed catheters and 4.0 in surgically placed ones (p < 0.001). Average catheter life-span was similar for the two placement methods (100 +/- 23 days). CONCLUSION: Radiological placement is consistently more reliable than surgical placement. There are fewer placement complications and fewer catheter infections overall.

Angiotropic lymphoma: report of a case with histiocytic features.

Angiotropic lymphoma, also known as intravascular lymphomatosis, is characterised by widespread intravascular proliferation of malignant lymphoid cells, usually without evidence of focal disease. A case of a 52 year old man referred for investigation of a two year history of pyrexia of unknown origin, skin rash and multiple organ failure is described. Angiotropic lymphoma was seen in gastric, colonic and skin biopsy specimens, and review of an earlier skin biopsy specimen showed similar morphological features. In contrast to previous cases which showed B or T cell differentiation, immunohistochemical examination was positive for histiocyte markers. Molecular studies showed no evidence of immunoglobulin heavy chain gene or T cell receptor gene rearrangement. The patient responded to combination chemotherapy, comprising cyclophosphamide, doxorubicin, etoposide, and prednisolone. This case highlights the fact that advanced lymphoma may be present without evidence of focal disease and that the diagnosis may be missed easily both clinically and histologically.

G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial.

We have undertaken a prospective randomized study in 90 patients with relapsed or resistant lymphomas to assess the value of G-CSF (lenograstim) in the acceleration of myeloid recovery after peripheral blood stem cell transplantation (PBSCT). A common regimen of cyclophosphamide 1.5 g/m2 on day 1 and lenograstim 263 microg s.c. on days 2-10 with two aphereses on days 10 and 11 was used for stem cell mobilization. 77% of patients achieved an adequate PBSC collection in two harvests (> 2 x 10(8) MNC/kg or > 2 x 10(6) CD34+ cells/kg). 65 patients went on to receive high-dose BEAM chemotherapy and engraftment data was available for 62. 34 patients had been randomized to receive lenograstim 263 microg/d s.c. and 28 to no growth factor. The median time to ANC > 0.5 x 10(9)/l was 9 d in the lenograstim arm versus 12.5 d in the no-lenograstim arm (P=0.0001). This was associated with a median duration of time in hospital post PBSCT of 13 d in the lenograstim arm versus 15.5 d in the no-lenograstim arm (P=0.0002). Median days to platelet independence, platelet transfusions, incidence of infection and red cell transfusion were the same in both arms. These data indicate that lenograstim significantly accelerated myeloid recovery after PBSCT and shortened the duration of hospital stay.

Analysis of the colonization of unirradiated and irradiated SCID mice by human lymphoma and non-malignant lymphoid cells.

We have evaluated the severe combined immunodeficient (SCID) mouse as an in-vivo model for the study of non-Hodgkin's lymphomas (NHL). Characterization of the immune system of the animals in our SCID mouse colony was carried out to assess the numbers of lymphoid cells present, to determine natural killer (NK) cell activity as a function of age and to examine the histology of the lymphoid organs. In this study four human NHL established cell lines (Daudi, Namalwa, U937, MC116), lymphoma cells from four fresh NHL biopsies and normal peripheral blood mononuclear cells (PBMC) and bone marrow cells were investigated, after intraperitoneal injection into the mice. The presence of the human NHL cells in the peritoneum and spleen was assessed by FACS analysis. The colonization potential was investigated in a range of tissues by polymerase chain reaction (PCR) amplification of human repetitive sequences. These studies revealed clear differences in the abilities of the NHL cell types to colonize the SCID mice. Namalwa, Daudi and U937 cells demonstrated the highest efficiency of colonization and readily formed tumours, whereas MC116, the NHL biopsy cell populations and the non-malignant lymphoid cells showed little ability to survive and colonize other tissues in the SCID mice. Whole body irradiation of the SCID mice appeared to improve the survival of human PBMC, NHL biopsy cells and MC116 cells in the peritoneum, but had little effect on their colonization potential. The significance of these studies is discussed.

2D-gel analysis of protein synthesis profiles of different stages of chronic lymphocytic leukaemia.

Protein synthesis profiles of leukaemic cells from 15 chronic lymphocytic leukaemia (CLL) patients were analysed by 2D-electrophoresis of 35S-methionine labelled proteins. This series of CLL included patients with stage A (7), B (4) and C (4) disease. Although the protein synthesis profiles were similar in all cases, some consistent differences were noted between the different stages. The levels of synthesis of three proteins (approximately 35 kD size) were of particular interest. Two of these were always expressed in stage C CLL but either infrequently or not at all in stage A or B CLL. By contrast a third protein was expressed at a much reduced level in stage C compared to stages A or B. This type of analysis could prove invaluable for identifying proteins whose expression was intimately associated with the evolution of CLL.