Lymphoproliferative disease in antibody deficiency: a multi-centre study

We have undertaken a retrospective study of antibody deficient patients, with and without lymphoma, and assessed the ability of specific polymerase chain reaction (PCR) primers to determine if the detection of clonal lymphocyte populations correlates with clinical and immunohistochemical diagnosis of lymphoma. We identified 158 cases with antibody deficiency presenting during the past 20 years. Paraffin-embedded biopsy specimens or slides were available for analysis in a cohort of 34 patients. Of these patients, 29 had common variable immunodeficiency, one X-linked agammaglobulinaemia, one X-linked immunoglobulin deficiency of uncertain cause and three isolated IgG subclass deficiency. We have confirmed that lymphoma in antibody deficiency is predominantly B cell in origin. Clonal lymphocyte populations were demonstrated in biopsies irrespective of histology (16/19 with lymphoma and 11/15 without). Isolated evidence of clonality in biopsy material is therefore an insufficient diagnostic criterion to determine malignancy. Furthermore, our data suggest that clonal expansions are rarely the result of Epstein-Barr virus-driven disease.     

Best practice in primary care pathology: review 1

This first best practice review examines four series of common primary care questions in laboratory medicine, namely: (i) measurement and monitoring of cholesterol and of liver and muscle enzymes in patients in the context of lipid lowering drugs, (ii) diagnosis and monitoring of vitamin B12/folate deficiency, (iii) investigation and monitoring of paraprotein bands in blood, and (iv) management of Helicobacter pylori infection. The review is presented in a question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.     

The interaction of lead exposure and pregnancy.

The toxic effects of low-level lead exposure have been the subject of a good deal of research and media attention in recent times. In most countries, the acceptable occupational exposure limit for lead is being progressively decreased as the adverse health effects of lead are being identified at levels approaching those found in non-occupational environments. Due to the sensitive nature of the fetus to hazardous substances, the exposure to lead of the unborn child via maternal sources is of critical concern. Preterm delivery, congenital abnormalities and decreases in growth stature have all been associated with prenatal lead exposure at "acceptable" levels. There is an accumulation of evidence which indicates that maternal exposures prior to conception can play an important role in determining blood lead levels during pregnancy. In light of these observations the practice of removing the pregnant woman from lead sources may be of questionable value with regards to providing sufficient protection for the fetus. This article reviews the relevant literature pertaining to the mobilization of lead from bone during pregnancy and the toxicity of low-level lead exposure to the fetus, and briefly discusses some factors which may affect this toxicity.     

The role of lymphokines in common variable hypogammaglobulinemia

Common variable (acquired) hypogammaglobulinemia (CVH) is a rare primary immunodeficiency disease of great interest as an immunological model of defects in antibody production. In this article, Gavin Spickett and John Farrant discuss evidence of abnormalities in lymphokine production and responses in the generation of the functional failure. It is not yet clear whether the B cell is intrinsically abnormal or lacks appropriate signals, but the block appears to occur in the differentiation phase of B cells, since membrane (but not secreted) IgG is made. Some T-cell defects also occur in this disease. The cause of CVH is unknown, although a viral aetiology has been suggested. Better understanding of lymphokine networks may allow the provision of specific signals to overcome the block in antibody production.     

1H NMR as a non-invasive probe of amniotic fluid in insulin dependent diabetes mellitus

Ten amniotic fluid samples obtained from third trimester pregnant women suffering from insulin dependant diabetes mellitus were analysed by 1H-NMR and compared to ten samples from a group of normal volunteers. A subset of the metabolites identified; valine, lactate, alanine, acetate, citrate and glucose were quantitated using standard addition methods. Apart from valine and citrate, a general diminution in the concentration of each of these species was found, especially glucose, in the diabetic group. The abnormally low glucose levels in the diabetic group are suggestive of infection in the patient group. However, the depressed lactate levels in the diabetic group suggest that in these cases the fetus was not subjected to stress.     

The influence of dietary citrate on the absorption and retention of orally ingested lead

The influence of dietary citrate on the toxicity of orally ingested lead was investigated in male weanling mice. Twenty-four animals were divided into three equal groups. Group 1 served as controls, groups 2 and 3 were given 20 g lead (as lead acetate) per g/diet, group 3 also received 4% sodium citrate in the diet.After 5 weeks, blood and tissue lead levels were measured. All mice given lead-supplemented diets had higher concentrations of lead in blood, liver, kidney, brain and bone than the control group, but the increase was significantly greater in the group given 4% sodium citrate in the diet. This work demonstrated that dietary citrate at levels which can be present in food significantly increases lead toxicity.