The impact of pain on spiritual well-being in people with a spinal cord injury.

STUDY DESIGN: The study uses a cross-sectional, group comparison, questionnaire-based design. OBJECTIVES: To determine whether spinal cord injury and pain have an impact on spiritual well-being and whether there is an association between spiritual well-being and measures of pain and psychological function. SETTING: University teaching hospital in Sydney, New South Wales, Australia. METHODS: Questionnaires evaluating pain, psychological and spiritual well-being were administered to a group of people with a spinal cord injury (n=53) and a group without spinal cord injury (n=37). Spiritual well-being was assessed using the Functional Assessment of Chronic Illness and Therapy - Spirituality Extended Scale (FACIT-Sp-Ex). Pain and psychological function were also assessed using standard, validated measures of pain intensity, pain interference, mood and cognition. RESULTS: Levels of spiritual well-being in people with a spinal cord injury were significantly lower when compared with people without a spinal cord injury. In addition, there was a moderate but significant negative correlation between spiritual well-being and pain intensity. There was also a strong and significant negative correlation between depression and spiritual well-being and a strong and significant positive correlation between spiritual well-being and both pain self-efficacy and satisfaction with life. CONCLUSION: Consequences of a spinal cord injury include increased levels of spiritual distress, which is associated, with higher levels of pain and depression and lower levels of pain self-efficacy and satisfaction with life. These findings indicate the importance of addressing spiritual well-being as an important component in the long-term rehabilitation of any person following spinal cord injury. SPONSORSHIP: This study was supported by grant funding from the Australian and New Zealand College of Anaesthetists, and the National Health and Medical Research Council of Australia.

Thalamic activity and biochemical changes in individuals with neuropathic pain after spinal cord injury.

There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry, and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. To clarify this subject, we compared brain activity and biochemistry in 12 people with below-level neuropathic pain after complete thoracic spinal cord injury with 11 people with similar injuries and no neuropathic pain and 21 age- and gender-matched healthy control subjects. Quantitative arterial spinal labelling was used to measure thalamic activity, and magnetic resonance spectroscopy was used to determine changes in neuronal variability quantifying N-acetylaspartate and alterations in inhibitory function quantifying gamma amino butyric acid. This study revealed that the presence of neuropathic pain is associated with significant changes in thalamic biochemistry and neuronal activity. More specifically, the presence of neuropathic pain after spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content, and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain.

Brain anatomy changes associated with persistent neuropathic pain following spinal cord injury.

Persistent neuropathic pain commonly occurs following spinal cord injury (SCI). It remains one of the most challenging management problems in this condition. In order to develop more effective treatments, a better understanding of the neural changes associated with neuropathic SCI pain is required. The aim of this investigation was to use diffusion tensor imaging (DTI) to determine if persistent neuropathic pain following SCI is associated with changes in regional brain anatomy and connectivity. In 23 subjects with complete thoracic SCI, 12 with below-level neuropathic pain and 11 without pain, and 45 healthy control subjects, a series of whole-brain DTI scans were performed. The mean diffusivity (MD) of each voxel was calculated and values compared between groups. This analysis revealed that neuropathic pain following SCI is associated with significant differences in regional brain anatomy. These anatomical changes were located in pain-related regions as well as regions of the classic reward circuitry, that is, the nucleus accumbens and orbitofrontal, dorsolateral prefrontal, and posterior parietal cortices. The right posterior parietal cortex projected to most regions that displayed an anatomical change. Analysis of the fiber tracts connecting areas of MD differences revealed no significance differences in MD values between the SCI pain, SCI no pain, and control groups.

Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury.

The most obvious impairments associated with spinal cord injury (SCI) are loss of sensation and motor control. However, many subjects with SCI also develop persistent neuropathic pain below the injury which is often severe, debilitating and refractory to treatment. The underlying mechanisms of persistent neuropathic SCI pain remain poorly understood. Reports in amputees describing phantom limb pain demonstrate a positive correlation between pain intensity and the amount of primary somatosensory cortex (S1) reorganization. Of note, this S1 reorganization has also been shown to reverse with pain reduction. It is unknown whether a similar association between S1 reorganization and pain intensity exists in subjects with SCI. The aim of this investigation was to determine whether the degree of S1 reorganization following SCI correlated with on-going neuropathic pain intensity. In 20 complete SCI subjects (10 with neuropathic pain, 10 without neuropathic pain) and 21 control subjects without SCI, the somatosensory cortex was mapped using functional magnetic resonance imaging during light brushing of the right little finger, thumb and lip. S1 reorganization was demonstrated in SCI subjects with the little finger activation point moving medially towards the S1 region that would normally innervate the legs. The amount of S1 reorganization in subjects with SCI significantly correlated with on-going pain intensity levels. This study provides evidence of a link between the degree of cortical reorganization and the intensity of persistent neuropathic pain following SCI. Strategies aimed at reversing somatosensory cortical reorganization may have therapeutic potential in central neuropathic pain.

Anatomical changes in human motor cortex and motor pathways following complete thoracic spinal cord injury.

A debilitating consequence of complete spinal cord injury (SCI) is the loss of motor control. Although the goal of most SCI treatments is to re-establish neural connections, a potential complication in restoring motor function is that SCI may result in anatomical and functional changes in brain areas controlling motor output. Some animal investigations show cell death in the primary motor cortex following SCI, but similar anatomical changes in humans are not yet established. The aim of this investigation was to use voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to determine if SCI in humans results in anatomical changes within motor cortices and descending motor pathways. Using VBM, we found significantly lower gray matter volume in complete SCI subjects compared with controls in the primary motor cortex, the medial prefrontal, and adjacent anterior cingulate cortices. DTI analysis revealed structural abnormalities in the same areas with reduced gray matter volume and in the superior cerebellar cortex. In addition, tractography revealed structural abnormalities in the corticospinal and corticopontine tracts of the SCI subjects. In conclusion, human subjects with complete SCI show structural changes in cortical motor regions and descending motor tracts, and these brain anatomical changes may limit motor recovery following SCI.

A phase 2 clinical trial comparing Ro 48-6791, a new short-acting benzodiazepine, with propofol for induction of anaesthesia.

A phase 2, single-blinded, randomized, multicentre trial was conducted to compare recovery times from anaesthesia between patients induced with a new short-acting benzodiazepine Ro 48-6791 (Hoffman-La Roche, Sydney, N.S.W.) or propofol. Seventy-six patients were randomly allocated to receive either Ro 48-6791 or propofol for induction followed by a standardized anaesthetic. Alertness and ambulatory function during recovery were scored by a rater blinded to treatment group. Mean time to awakening was longer for the Ro 48-6791 group (15 min), compared with propofol (7 min, P < 0.001), as was mean time to full clinical recovery (116 min vs 75 min respectively, P = 0.002). Both groups showed similar cardiovascular stability following induction, but shorter apnoea times were demonstrated for Ro 48-6791 (48s vs 133, P < 0.001). The longer recovery times with Ro 48-6791 would make this drug a less suitable sole induction agent than propofol for routine use in day stay surgery. Further studies of Ro 48-6791 should pay particular attention to the effect of dose reduction on recovery profile.

Double modulation of 5-fluorouracil with interferon alpha 2a and high-dose leucovorin: a phase I and II study.

Twenty-nine patients with adenocarcinomas of gastrointestinal or unknown primary, and three with advanced neuroendocrine tumours, were entered into a study of bolus plus infusional 5-fluorouracil (FUra) modulated with high-dose leucovorin (LV) and recombinant interferon alpha 2a (IFN-alpha). Successive cohorts of > or = 4 patients received IFN-alpha at 1.5, 3, 4.5, 6 and 9 MU on alternate days throughout the treatment period. The FUra/LV regimen consisted of: LV 200 mg m-2 i.v. infusion over 2 h, FUra 400 mg m-2 i.v. bolus then FUra 400 mg m-2 i.v. infusion over 22 h, all repeated on day 2, on a 14-day cycle. FUra was given at 75% dose for the first course, increasing (in the absence of WHO grade > or = 2 toxicity) to 87.5% for the second and 100% for subsequent courses up to a maximum of 12. The maximum tolerated dose (MTD) of IFN-alpha was 6 MU on alternate days, with 7/8 patients at 9 MU requiring dose reductions. At 6 MU IFN-alpha, the MTD of FUra was not exceeded at 100% (i.e. 400 mg m-2 bolus and infusion, days 1 and 2), and FUra-related toxicities (mucosal, haematological, dermatological) were extremely mild. Twenty-nine patients were assessable for tumour response, among whom WHO criteria partial responses were seen in 7/14 with colorectal, 1/4 with gastric, 0/1 with pancreatic, 1/3 with neuroendocrine and 3/6 with unknown primaries. Median response duration was 51 weeks. Minor responses and stable disease were seen in a further six patients. Median survival of patients with advanced adenocarcinomas was 9 months, with 33% surviving beyond 18 months. This schedule offers a safe way of co-administering FUra, LV and IFN-alpha. The addition of IFN-alpha, while causing significant independent toxicity, does not significantly increase the dose-limiting mucosal toxicities of FUra/LV. Further investigation is required to determine the contribution of IFN-alpha to the anti-tumour activity of the combination.

A randomized trial of two etoposide schedules in small-cell lung cancer: the influence of pharmacokinetics on efficacy and toxicity.

PURPOSE: Etoposide is a schedule-dependent drug, as demonstrated by the superiority of 5 consecutive daily infusions over a continuous 24-hour infusion in patients with small-cell lung cancer. A randomized trial has therefore been conducted to compare an extended 8-day regimen with the 5-day schedule. PATIENTS AND METHODS: Ninety-four patients with small-cell lung cancer (35 limited disease, 59 extensive disease) were randomized to receive single-agent etoposide 500 mg/m2, either as 5 daily 2-hour infusions of 100 mg/m2 or as 8 daily 75-minute infusions of 62.5 mg/m2, both repeated every 3 weeks for six cycles. Single-agent carboplatin was administered at relapse in both arms of the study. Patients were stratified at randomization according to extent of disease and Karnofsky performance status (KPS). RESULTS: The overall response rate was 81% in the 5-day arm and 87% in the 8-day arm, with median survival durations of 7.1 and 9.4 months, respectively (no significant differences). The time over which plasma etoposide exceeded low plasma concentrations was significantly longer in patients who responded compared with patients who did not respond. This was most significant for time at concentrations greater than 1, 1.5, and 2 micrograms/mL. Hematologic toxicity was significantly worse in the 5-day arm of the study (cycle no. 1 nadir neutrophil count, 0.8 x 10(9)/L v 1.7 x 10(9)/L). Stepwise regression analysis found duration of exposure to plasma etoposide greater than 3 micrograms/mL to be predictive of nadir neutrophil count and duration of exposure to plasma etoposide greater than 2 micrograms/mL to be predictive of nadir WBC count. CONCLUSION: The 5-day and 8-day regimens had equivalent activity in small-cell lung cancer. A pharmacokinetic association between concentrations of etoposide and response and toxicity was found. Antitumor activity was associated with the maintenance of lower levels of etoposide than found to be associated with hematologic toxicity. This supports the hypothesis that the schedule of etoposide administration may affect efficacy and toxicity, and that prolonged exposure to low concentrations of etoposide may improve the therapeutic ratio for this drug.

Tumour markers for prediction of survival and monitoring of remission in small cell lung cancer.

Levels of the tumour markers neurone specific enolase (NSE), lactate dehydrogenase (LDH), chromogranin A (ChrA) and carcinoembryonic antigen (CEA) were measured in serum taken at presentation and during treatment, remission and relapse from 154 patients who received chemotherapy for small cell lung cancer at a single centre over a 6 year period. At presentation NSE was the most frequently elevated marker, being raised in 81% of patients and significantly higher in extensive as opposed to limited disease, as were LDH and ChrA. The response rate to therapy was best correlated with presentation level of ChrA, being 79% for those whose levels were within twice the upper limit of normal and 51% above (P < 0.01). Multivariate regression analysis showed NSE, performance status and albumin at presentation to be the best independent predictors of survival. Patients with NSE below twice the upper limit of normal, Karnofsky performance status of 80 or above and albumin 35 g l-1 or above had a median survival of 15 months with 25% alive at 2 years, whilst those with NSE above twice normal, Karnofsky below 80 and albumin less that 35 g l-1 had all died by 8 months. Changes in marker levels during therapy were of low predictive value for outcome although the finding of rising NSE during chemotherapy after an initial fall correlated with significantly reduced duration of remission. There was a strong inverse correlation between the NSE level at the time of response and duration of remission (P < 0.0001). Prediction of relapse was most reliable with ChrA, 52% of patients having rising levels before clinical evidence of disease recurrence.

Indomethacin and protein binding of methotrexate.

Indomethacin, a non-steroidal anti-inflammatory drug is known to increase the efficacy and toxicity of methotrexate, the widely used anti-cancer drug in man. The mechanism for this interaction has not been clearly established. However, since these drugs bind with albumin, a possible displacement of methotrexate by indomethacin from albumin might explain this interaction. To investigate the possible interaction an in-vitro protein-binding displacement study was carried out in 17 normal volunteers and in two groups of eight cancer patients. One group of patients had active disease and the other was in complete clinical remission. Serum samples were obtained and protein levels estimated. The protein binding of methotrexate was measured alone and with indomethacin using equilibrium dialysis. Statistical analysis of results suggested that the binding of methotrexate is not influenced by indomethacin, confirming that methotrexate is not displaced by indomethacin.

Management of stage II Hodgkin's disease: 15 years experience at St. Bartholomew's Hospital.

One hundred seventy-seven consecutive patients with newly diagnosed stage II Hodgkin's disease (HD) (supradragmatic 157; infra diaphragmatic 20) were treated at St. Bartholomew's Hospital on the basis of pathologic stage (PS) in 84 (IIA 69; IIB 15) and clinical stage (CS) in 93 (IIA 33, IIB 60) between January 1968 and December 1984. The median follow up is 13 years. Overall, complete remission (CR) was achieved in 143 patients (75%) of whom 53 have had a recurrence. One hundred twenty-seven patients remain alive, the cumulative predicted survival at 15 yrs being 70%. Mantle radiotherapy was prescribed to 88 patients with supradiaphragmatic HD, of whom 75 entered CR and 9 achieved good partial remission (GPR) (95%). The duration of remission correlated strongly with ESR (greater than 50 mm/h) and mediastinal thoracic ratio (less than 33% vs. greater than 33%) in a multivariate analysis (p = 0.05 and 0.02, respectively). 46/88 patients remain in continuous first remission, the median duration of remission having not reached at 15 years. Combined modality therapy or chemotherapy alone was prescribed to 69 patients with supradiaphragmatic HD, CR being achieved in 51 patients and GPR in 8 at the completion of all therapy. 48/59 patients continue in first remission. The duration of remission of patients receiving combined modality therapy or CT alone was significantly longer (p = 0.002) than that of patients receiving RT alone, in spite of the fact that the former group comprised predominantly of patients with unfavourable features.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein binding of indomethacin, methotrexate and morphine in patients with cancer.

The in vitro protein binding of indomethacin, morphine and methotrexate has been studied in two groups of ten patients each suffering from different types of cancers and compared with twenty normal adult subjects. One group of patients had active disease and the other group was in complete clinical remission. Serum samples were obtained from each subject and the concentrations of albumin and alpha-1 acid glycoprotein (AGP) were measured. Protein binding of drugs was determined using equilibrium dialysis. Alpha-1 acid glycoprotein levels were increased in patients and this effect was more pronounced in active disease (1802 +/- 1025 mg/l) than in remission (931 +/- 273 mg/l). Albumin levels were reduced in active disease (47.67 +/- 15.91 milligrams), but not in remission (61.86 +/- 6.62 milligrams), as compared to control values (58.98 +/- 9.9 milligrams). The protein binding of methotrexate and indomethacin were both reduced in active disease (34.17 +/- 7.12% and 96.26 +/- 0.93% respectively) in comparison with normal subjects (39.33 +/- 4.68% and 96.89 +/- 0.47% respectively), but that of morphine was not changed. In patients there was a strong negative correlation between albumin and alpha-1 acid glycoprotein levels (r = -0.75, p < 0.01) but the correlation in controls was not significant. This study found only weak association between the binding of the drugs studied and the protein levels. It is concluded that reduction in methotrexate dose levels may reduce toxicity in patients with active cancer.

Recombinant human granulocyte macrophage colony stimulating factor following alternating non cross resistant chemotherapy in Hodgkin's disease.

Fourteen patients with Hodgkin's disease (two previously untreated, 12 following relapse or with refractory disease) were treated with a combination chemotherapy regimen comprising chlorambucil, vinblastine, procarbazine, prednisolone, etoposide, vincristine and adriamycin administered on days 1-8. Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (mammalian glycosylated, Sandoz/Schering-Plough) was administered after alternate cycles of chemotherapy from day 10 for 7 days by continuous intravenous (i.v.) infusion in 12 patients in a dose finding study (dose: 2 micrograms/kg/day in four patients, 4 micrograms/kg/day in four patients and 8 micrograms/kg/day in four patients) and by daily subcutaneous (s/c) injections in two patients (8 micrograms/kg/day). There was a rapid peripheral leucocytosis following the rhGM-CSF, reaching a peak at 1-2 days in 12/14 patients. The initial leucocytosis was composed of neutrophils followed by a rise in immature myeloid cells. There was no difference observed in the duration or depth of the nadir following chemotherapy or in the rate of recovery of peripheral white cell counts between cycles with and without rhGM-CSF in patients treated with 2 and 4 micrograms/kg/day. At the dose of 8 micrograms/kg/day, 3/6 patients had a shorter nadir duration in the cycle with rhGM-CSF, compared with cycle without rhGM-CSF. There was no difference in frequency of infection in cycles with and without rhGM-CSF. Following chemotherapy, six patients achieved clinical remission, six partial remission and two had progressive disease.

A less toxic regimen of 5-fluorouracil and high-dose folinic acid for advanced gastrointestinal adenocarcinomas.

The combination of high-dose folinic acid with 5-fluorouracil has shown improved response rates in several trials in advanced colorectal carcinoma. This however is at the expense of increased toxicity: regimens using weekly bolus injections produce diarrhoea in most patients and occasional toxic deaths from this, whilst those using daily injections for one week in four report both diarrhoea and severe oral mucositis. Both types of regimen have significant rates of myelosuppression. A recent report described a different schedule of 5-fluorouracil and folinic acid, which appeared better tolerated but equally active (De Gramont et al., 1988). Here we report results using the same programme, in 64 patients with advanced adenocarcinomas. (Forty three colorectal, ten gastric, six pancreatic and five of unknown primary.) Patients received 200 mg m-2 folinic acid by infusion over 2 h followed by an IV bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 400 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for a total of six to 12 courses depending upon the response. The overall response rate was 26% in 62 evaluable patients. No toxicity greater than WHO Grade II occurred. Diarrhoea and mucositis did occur in around 10% of treatments but were not troublesome. No febrile neutropenic episodes were seen. Despite previous reports which described only modest activity for this combination against stomach cancers, this regimen demonstrates low toxicity but retains good activity in the palliative treatment of both gastric and colonic adenocarcinomas.

Phase II trial of UFT in advanced colorectal and gastric cancer.

A phase II trial of continuous oral therapy with UFT, a combination of uracil and the 5-fluorouracil analogue 1-(2-tetrahydrofuryl)-5-fluorouracil (Futraful, Ftorafur), was conducted in 40 patients with advanced colorectal cancer and 18 patients with advanced gastric cancer. Six partial responses were seen in the 36 evaluable patients with colorectal cancer (response rate 16.6%; 95% confidence limits 6.4-32.8%), and one partial response was seen in the 16 evaluable patients with gastric cancer (response rate 6%; 95% confidence limits 0.27-30.2%). The overall toxicity of the treatment was low, and all patients were treated as outpatients. The results suggest that oral UFT has comparable activity to standard regimes of 5-fluorouracil, and because of the convenience of oral administration is a useful therapy in the management of patients with advanced colorectal cancer.

Radiotherapy for stage I Hodgkin's disease: 20 years experience at St Bartholomew's Hospital.

One hundred and one consecutive patients with newly diagnosed stage I Hodgkin's disease (HD) received treatment at St Bartholomew's Hospital, between 1968 and 1987, with a median follow-up of 12 years. Eleven patients have been excluded from detailed analysis because they either received involved field radiotherapy (RT) or radiotherapy with chemotherapy or were lost to follow-up. Actuarial analysis predicts 78% to be alive and without relapse of Hodgkin's disease at 15 years. Ninety evaluable patients (clinical stage (CS) 24; pathological stage (PS) 66) received either mantle or inverted 'Y' RT and form the basis of this analysis. The median age was 33 years (63 men, 27 women). Histology at presentation was nodular sclerosing (39), lymphocytic predominant (27) or mixed cellularity (24). The presenting site was neck (78), axilla (6) groin (4) and mediastinum (2). Complete remission was achieved in all evaluable patients, the actuarial proportion in remission being 75% at 15 years. Factors predictive of a prolonged remission were pathological staging versus clinical staging (P = 0.02) and lymph node size less than 3 cm (P = 0.04). Actuarial overall survival in these 90 patients was 75% at 15 years and none of the above factors correlated with survival. Relapse of HD has occurred in 18 patients (5 within RT field, 10 without and 3 in both). Second remission was achieved in 15/18. The actuarial rate of second remission and survival was 40% at 10 years. Sixteen patients have died, 7 of Hodgkin's disease, 7 of unrelated causes and 2 of second malignancy. A further 3 patients who developed second malignancy are still alive. At 15 years the actuarial mortality related to HD was 12%. These results confirm the importance of long follow up to assess the efficacy of primary therapy.

A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.

Autoimmune haemolytic anaemia associated with malignant peritoneal mesothelioma.

A 57-year-old man with a history of pulmonary asbestosis was incidentally found to have benign mesothelial hyperplasia of the peritoneum at hernia repair. Five months later he developed a Coombs positive haemolytic anaemia of the IgG-C3d type caused by non specific IgG antibodies. At that time no underlying cause for the anaemia was found. The anaemia responded to steroids, but remained steroid dependent. Six months after the diagnosis of the anaemia, a malignant peritoneal mesothelioma was found at laparotomy. The association between malignant mesothelioma and autoimmune haemolytic anaemia has been reported on one previous occasion. The description of a second case suggests that the association is not purely coincidental and that malignant mesothelioma should be added to the list of solid tumours that can be associated with autoimmune haemolytic anaemia. The finding of red blood cells coated with IgG and C3d in this as well as in other cases adds further evidence to the hypothesis that a quinidine type mechanism of haemolysis might be responsible for Coombs positive haemolytic anaemia associated with solid tumours.