Necrotising external otitis caused by Aspergillus wentii: a case report.

Necrotising external otitis (NEO) is a destructive, potentially fatal, infection usually seen in elderly diabetics or the immunocompromised. The commonest causative organism is Pseudomonas but immunocompromised patients are additionally susceptible to opportunistic infections. Here we describe the first reported case of NEO caused by a previously unknown human pathogen--Aspergillus wentii. A review of the literature reveals that fungal NEO is associated with a high rate of cranial nerve palsies suggesting that infections are not being treated rapidly enough to prevent morbidity. Fungal infection should be considered early in immunocompromised patients and microbiological diagnosis should be obtained wherever possible.

D-dimers as a screening test for venous thromboembolism in pregnancy: is it of any use?

In non-pregnant women, D-dimers are used successfully to aid diagnosis of suspected pulmonary embolus (PE), as they have high sensitivity, moderate specificity and high negative predictive value. However, D-dimer levels are physiologically raised in pregnancy and thus overlap the values normally associated with PE. The aim of this retrospective study therefore was to investigate the use of D-dimer levels as a screening test for suspected PE in pregnancy and to determine if a negative D-dimer level could exclude the diagnosis in pregnant women. A total of 37 women suspected of PE had both ventilation perfusion (VQ) scans and D-dimer levels performed. Thirteen were reported as having a low probability of PE following VQ scan, while 24 were thought to have a moderate or high probability of PE. Women who had a low probability of PE following VQ scanning were found to have D-dimer levels ranging from 0.25-2.2 mg/l, while women who had a high probability of PE following scanning had D-dimer levels ranging from 0.31-1.74 mg/l. The sensitivity and specificity of D-dimer as a test for suspected PE in pregnancy was calculated to be 0.73 and 0.15 respectively, while the negative likelihood ratio was 1.8. Current guidelines advocate the use of a negative D-dimer result to exclude the diagnosis of PE in pregnancy. However, this study suggests that D-dimer testing in pregnancy has a high negative likelihood ratio and should not be used. Larger prospective observational studies are required to collaborate the findings from this study.

Inherited protein C deficiency, protein S deficiency and hyperhomocysteinaemia in a patient with hereditary spherocytosis.

We report a family with hereditary spherocytosis in whom there is, in addition, a cluster of genetic predispositions to thrombosis. Although inherited prothrombotic abnormalities are prevalent in the general population, the likelihood of this combination of abnormalities being found in a single family is extremely low. The management of such high risk individuals is discussed.

A toxic interaction between mitomycin C and tamoxifen causing the haemolytic uraemic syndrome.

A comparison of patients receiving combination chemotherapy with mitomycin C, mitozantrone and methotrexate (3M) with and without tamoxifen for treatment of primary breast cancer indicates an increased risk of anaemia (P < 0.0001) and thrombocytopenia (P < 0.001), but not leucopenia for patients receiving tamoxifen with their chemotherapy compared to those receiving the chemotherapy alone. Furthermore, 9 out of 94 patients receiving tamoxifen with 3M developed progressive anaemia, thrombocytopenia and abnormal renal function as early features of microangiopathic haemolytic anaemia, progressing on to various degrees of the haemolytic uraemic syndrome (HUS). This is only rarely seen with patients receiving mitomycin C alone at higher doses than used in the 3M combination and in the presence of active metastatic disease. This syndrome can be fatal and 1 of our 9 patients died. These observations indicate that there may be an interaction between tamoxifen and mitomycin C, causing an increased incidence of anaemia, thrombocytopenia and an increased risk of HUS. The combination of these two drugs should be avoided or carefully monitored.

Antilymphocyte globulin therapy enhances impaired function of natural killer cells and lymphokine activated killer cells in aplastic anaemia.

MHC-unrestricted cytotoxic lymphocytes, namely natural killer (NK) and lymphokine activated killer (LAK) cells, have been implicated in the regulation of haemopoiesis. To investigate the possible role of these lymphocytes in the pathogenesis of aplastic anaemia (AA), we studied their functions in the peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) of patients with AA treated with antilymphocyte globulin (ALG). Before treatment, both NK and LAK activities in the PBMC of 25 patients were low (NK = 1.9 +/- 2.1 x 10(3) LU/l) LAK = 4.7 +/- 3.6 x 10(3) LU/l) compared to normal (NK = 6.0 +/- 3.0 x 10(3) LU/l, LAK = 10.0 +/- 3.5 x 10(3) LU/l) or multiply transfused (NK = 7.8 +/- 6.6 x 10(3) LU/l, LAK = 25.2 +/- 13.6 x 10(3) LU/l) controls. The NK and LAK activities in the BMMC in AA patients were not significantly different from those in PBMC. In all patients with low LAK and NK activities pre ALG there was an increase in activity 2-24 weeks after therapy which eventually reached normal levels and which was maintained for up to 2 years. Analysis of lymphocyte phenotypes in AA patients before treatment showed both significantly low mean proportion and absolute numbers of CD16+ cells compared to normals, which increased after therapy. Changes in MHC-unrestricted cytotoxicity and lymphocyte phenotypes post therapy were not correlated with haemopoietic recovery. These data suggest that ALG treatment can enhance the functions of MHC-unrestricted lymphocytes independently from haemopoiesis. It is unlikely that these cells play a role in the pathogenesis of AA.

HIV-disease and bone marrow changes: a study of 60 cases.

We report our experience of peripheral blood and bone marrow changes in patients with HIV disease. Abnormalities were most commonly seen in patients with advanced disease. In AIDS group IV patients (CDC classification) anaemia (92%) neutropenia (85%) monocytopenia (75%) and thrombocytopenia (61%) have their highest incidence, the reason being a combination of factors such as infection, myelosuppressive drugs and HIV infection itself. Bone marrow examinations were performed most commonly for microbiological culture (25%) and the investigation of anaemia (16%). Morphological changes in the bone marrow were non-specific and not pathognomic; however erythroid hypoplasia was found to be a distinctive feature associated with MAI infection. The procedure provided a high yield for microbiological culture, particularly in MAI infection.