Listeria meningitis and paté.

Listeria meningitis occurred in a 63 year old man who was in complete haematological remission following chemotherapy for acute myeloid leukaemia. The patient had followed Department of Health advice to immunocompromised patients and had avoided soft cheeses, cook-chill meals, and salads. He had, however, recently eaten paté produced in Belgium. This was no longer available for examination but a coincidental survey of paté in the Cardiff area found Listeria monocytogenes in 16 out of 73 samples. Paté should be included in the list of foods to be avoided by immunocompromised patients.

Blood viscosity and hearing levels in the Caerphilly Collaborative Heart Disease Study.

Data from 342 men who are participants in the Caerphilly Collaborative Heart Disease Study were used to replicate a previous report of a significant relationship between measures of whole-blood viscosity and hearing levels in persons with sensorineural hearing impairment. In the unselected data, there were significant relationships between measures of whole-blood viscosity at high shear rates and hearing threshold levels at 2000 and 4000 Hz, even after accounting for the effects of age and socioeconomic group. In a subset of the data containing 124 persons selected on the basis of likely sensorineural hearing impairment, there were significant relationships between whole-blood viscosity and hearing level at all frequencies, with stronger effects at the higher frequencies. The data support the contention of a potentially important relationship between whole-blood viscosity and sensorineural hearing impairment.

Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm.

Treatment with erythropoietin is highly effective and beneficial if given with care. In view of its cost, however, it is essential to exclude and treat other causes of anaemia before considering using this hormone. After treatment is started the important points for success are regular review of iron availability state combined with a slow correction of the anaemia. Failure of response requires a thorough search for a possible cause, which should be corrected before considering an increased dose of the hormone. Regular monitoring for potential complications, particularly a rise in blood pressure, is required.

The effect of iron deficiency on whole blood viscosity in polycythaemic patients.

Iron deficiency leads to a significant increase in whole blood viscosity in polycythaemic patients. This can be corrected by simultaneous treatment with iron and venesection. In patients with polycythaemia secondary to hypoxia the haemoglobin concentration may be increased by treating coexisting iron deficiency, without altering the whole blood viscosity, thus increasing oxygen availability to the tissues. Values for whole blood viscosity can be derived from the peripheral blood Hb and MCH, allowing therapeutic decisions to be made on the basis of a simple haematological examination.

Wiskott-Aldrich syndrome: fatal consequences of splenectomy in an unrecognised attenuated variant.

Monozygotic twin males with an attenuated variant of the Wiskott-Aldrich syndrome (WAS) are described. Diagnostic features included moderate thrombocytopenia with small platelet size and abnormal platelet aggregation responses, chronic eczema, depressed serum IgM and low isoagglutinin titre. Splenectomy was performed on one twin at age seven years who survived a complicating pneumococcal septicaemia ten days after the procedure, but who succumbed to fulminating infection three years later. The importance of recognising the attenuated variants of WAS is discussed.

Scanning electron microscopy of experimental Trichophyton mentagrophytes infections in guinea pig skin.

Trichophyton mentagrophytes invasion of guinea pig skin was examined by scanning electron microscopy. Biopsies were obtained daily for 12 days from experimental infection sites. Dermatophyte invasion, examined in detail by scanning electron microscopy of cross-sectioned, prefixed skin was evidenced by: the appearance of hyphae within the stratum corneum; follicular invasion by hyphae, which remained initially within the follicle wall; emergence of the hyphae from the wall into the follicular canal; proliferation of the fungus down the follicle, with furrowing of the follicle wall and hair shaft cuticle; penetration of hyphae into the hair shaft by subcuticular and transcuticular routes; and massive peripilar hyphal proliferation with arthrosporogenesis. A three-dimensional perception of the invasion sequence of a dermatophyte in guinea pig skin was obtained by scanning electron microscopy.

Visual micromethod for assay of fungal growth.

A visual micromethod for measuring antifungal effects on germination and growth is described. The antifungal agent griseofulvin and the fungus Trichophyton mentagrophytes were used as materials to compare the micromethod with a standard assay based on dry mycelial weight. The micromethod was more sensitive than the weight method in detecting the minimum inhibitory concentration of griseofulvin (0.18 and 35 microgram/ml, respectively). At higher concentrations of griseofulvin (22.5 microgram/ml), the micromethod measured minimal fungal growth that was undetectable on a weight basis. The micromethod showed that griseofulvin does not change the number of spores forming germ tubes. Progressively severe alterations in fungal morphology occured as the concentration of griseofulvin was increased from 0.09 to 22.5 microgram/ml.

The use of erythropoietin in renal failure.

The treatment of renal anaemia by recombinant human erythropoietin (EPO) is now well established. Several studies have examined the pharmacokinetics and efficacy of the drug given intravenously, intraperitoneally and subcutaneously and there is increasing evidence that the subcutaneous route has several advantages including the requirement for a lower dose. It is also important to stress the need for careful determination of baseline iron status of all patients before commencing EPO therapy. In the long term the extremely high iron stores of transfusion dependent patients will disappear. In the short term, however, the majority of the patients whose serum ferritin is less than 100 micrograms/l will require iron supplementation to allow an appropriate haemoglobin response. Alternatively, a fall in transferrin saturation to less than 20% is certainly an indication for iron supplementation and if oral iron therapy is not adequate then intravenous preparations may have to be considered. Although the anaemia of renal failure can be fully corrected by EPO, partial correction may be sufficient to reverse the problems of reduced exercise capacity, myocardial ischaemia and cardiomegaly which are frequently associated with end-stage renal disease. Partial correction will also result in a lesser rise in whole blood viscosity and, in turn, possibly reduce hypertension, thrombosis and increased peripheral resistance and thus lessen the side effects of EPO therapy.

Markers of the nutritional status in acutely ill elderly patients.

We recorded anthropometric and laboratory data in 98 sick old people on admission to a high-dependency unit. The measurement of triceps skinfold thickness and arm muscle area was feasible even in very ill people, while measurement of the body mass index was difficult and sometimes unreliable. Anthropometric measurements indicated that our study group was better nourished than a local population, with just 3 subjects (3%) being fat depleted and a further 4 (5%) being protein depleted. Serum albumin was the laboratory variable that correlated best with anthropometric parameters. However, it was low in 47% of the subjects, indicating that its lower reference value needs to be redefined in this select group.

Polycythaemia following renal transplantation: an association with azathioprine dosage?

Patients from a renal transplantation unit with an unusually high incidence of polycythaemia were divided into polycythaemic and control groups. The rate of rise of haemoglobin concentration was not significantly different in the two groups. The polycythaemic group received a significantly lower dose of azathioprine (p less than 0.005) and included more patients with polycystic disease than the control group (p less than 0.05). An effect of azathioprine on bone marrow function was suggested by the polycythaemic group also having a higher mean white cell count (p less than 0.02). Azathioprine dosage correlated negatively with post-transplantation polycythaemia regardless of the original cause of renal failure.

Rheological studies during treatment of renal anaemia with recombinant human erythropoietin.

Whole blood, plasma, and serum viscosity together with red cell deformability were measured before and during treatment of renal anaemia with recombinant human erythropoietin (EPO). Whole blood viscosity (WBV) progressively increased during the first 4 months of treatment in association with the rise in haemoglobin concentration. When the WBV was corrected to a standard haemoglobin concentration no change in blood viscosity was observed, neither was there any alteration in a derived index of red cell deformability, or in the plasma and serum viscosities. In addition, a direct measurement of red cell deformability using a filtration technique before EPO therapy was similar to that obtained in 30 healthy volunteers. There was no significant change in this parameter over the first 9 months of treatment. The rheological changes which occur with correction of anaemia with EPO can be explained solely by the increase in circulating haemoglobin mass rather than to any change in the properties of the plasma or red cells themselves.

Coagulation studies and fistula blood flow during erythropoietin therapy in haemodialysis patients.

An increased incidence of fistula thrombosis has been reported in haemodialysis patients treated with recombinant human erythropoietin (rHuEpo). The present study sought to investigate this problem by measuring fistula blood flow, blood viscosity, and a variety of tests of coagulation and haemostasis in a group of ten haemodialysis patients treated with rHuEpo. Fistula blood flow did not alter during the first 12 months of rHuEpo despite a significant increase in whole-blood viscosity. Bleeding time improved in all ten patients after 4 months of therapy, and this improvement was maintained at 12 months. There were no significant changes in one-stage prothrombin time, kaolin cephalin clotting time, whole-blood clotting time, prothrombin consumption index, plasma fibrinogen factor VII, factor VIII, antithrombin III, or platelet aggregability to ADP over the first 4 months of rHuEpo. In contrast, protein C decreased from 84.3 to 66.4% (P less than 0.01) and protein S from 124.1 to 68.3% (P less than 0.001) over the first 4 months. By 8 and 12 months, the concentrations of these substances had returned to pretreatment values. The levels of protein C and S attained at 4 months are known to predispose to thrombosis, and it is possible that this effect may contribute to the increased incidence of fistula thrombosis observed in haemodialysis patients treated with rHuEpo.

Haemoglobinopathy screening in a 'low-risk' area of the United Kingdom: South Glamorgan, Wales.

Figures collected over 2 1/2 years of screening of women attending the antenatal clinics of South Glamorgan, Wales, showed that the percentage of women identified as a risk for haemoglobinopathy trait (7.4%) was almost twice that estimated from the 1981 Census data (4.1%) and that the incidence of a thalassaemia trait in these women (0.38% beta; 0.68% alpha) was similar to that of an area of supposedly greater risk in London (0.46% beta; 0.42% alpha). Figures from one laboratory showed that without a scrutiny of all antenatal clinic blood counts for thalassaemic indices some thalassaemia traits will be missed. The apparent incidence of the HbS trait was 0.13%, and reasons for this being an underestimate are given.

The treatment of renal anaemia in CAPD patients with recombinant human erythropoietin.

Fifteen severely anaemic patients receiving CAPD were treated with subcutaneous recombinant human erythropoietin (Epo). Ten subjects had a good response with the haemoglobin concentration increasing from less than 8 g/dl to greater than 10 g/dl within 16 weeks. Four patients had a poor response, which was due to infection in two, myelofibrosis in one and unknown cause in another. Epo was ineffective in the remaining individual, probably due to the presence of occult metastatic carcinoma. Iron supplementation in the form of intravenous iron dextran was given to 12 patients when transferrin saturation decreased below 20%. There was a significant increase in red cell volume (P less than 0.005), with a decrease in plasma volume (P less than 0.005). Red cell iron turnover increased (P less than 0.05) but there was no change in red cell lifespan or deformability. Biochemical parameters remained unaltered, as did peritoneal function. Exercise duration improved (P less than 0.001), as did maximal oxygen consumption (P less than 0.01). Four patients required an increased dose of hypotensive drugs. Epo is a safe effective therapy for the anaemia of CAPD subjects.

HFE mutations, iron deficiency and overload in 10,500 blood donors.

People with genetic haemochromatosis (GH) accumulate iron from excessive dietary absorption. In populations of northern European origin, over 90% of patients are homozygous for the C282Y mutation of the HFE gene. While about 1 in 200 people in the general population have this genotype the proportion who develop clinical haemochromatosis is not known. The influence of HFE genotype on iron status was investigated in 10 556 blood donors. The allele frequencies of the C282Y and H63D mutations were 8.23% and 15.3% respectively. Heterozygosity for C282Y occurred in 1 in 7.9 donors, for H63D in 1 in 4.2 donors, and 1 in 42 were compound heterozygotes. Homozygosity for H63D occurred in 1 in 42 donors and 1 in 147 (72) were homozygous for C282Y. Mean values increased for transferrin saturation (TS) and serum ferritin (sFn), and decreased for unsaturated iron binding capacity (UIBC) in the order: donors lacking the mutations, H63D heterozygotes, C282Y heterozygotes, H63D homozygotes, compound heterozygotes and C282Y homozygotes, but serum ferritin (sFn) concentrations were no higher in H63D heterozygotes and C282Y heterozygous women than in donors lacking mutations. The percentage of donors failing the screening test for anaemia or of those with sFn < 15 microg/l did not differ among the genotype groups. C282Y and H63D heterozygotes and donors homozygous for H63D were at no greater risk of iron accumulation than donors lacking mutations, of whom 1 in 1200 had both a raised TS and sFn. The risk was higher for compound heterozygotes (1 in 80, P = 0.003) and for C282Y homozygotes (1 in 5, P < 0.0001). There was no correlation between sFn and either age or donation frequency in C282Y homozygotes. None of the 63 C282Y homozygous donors interviewed showed physical signs of overload or were aware of relatives with haemochromatosis. The Welsh Blood Service collects blood from about 140 000 people each year including an estimated 950 who are homozygous for HFE C282Y. They are probably healthy and unaware of any family history of iron overload.

Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin.

The long-term cardiorespiratory effects of recombinant human erythropoietin treatment were investigated in ten haemodialysis patients by means of maximum exercise testing, lung function tests, echocardiography, chest X-ray, and rheological assessment over 12 months. There were significant rises in exercise time (mean [SD] 13.2 [5.5] to 20.0 [6.2] min), maximum oxygen consumption (19.1 [7.0] to 25.0 [6.7] ml.min-1.kg-1), and anaerobic threshold (11.7 [3.6] to 15.4 [4.8] ml.min-1.kg-1) after 2 months of erythropoietin treatment. The improvements were maintained but not augmented on repeat testing after 4, 8, and 12 months of therapy. Carbon monoxide transfer [corrected] rose from 15.5 (2.9) to 18.6 (3.7) ml.min-1.mm Hg-1. There was a substantial reduction in exercise-induced cardiac ischaemia (eight patients had significant ST segment depression before erythropoietin, only one after 2 months' treatment, and none after 12 months' treatment), despite a significant rise in whole blood viscosity. Left ventricular mass, as estimated by echocardiography, progressively decreased from 354 (169) g to 251 (95) g after 12 months' treatment, and four patients showed a reduction in cardiothoracic ratio on chest X-ray.