An approach to the patient with urticaria.

Patients with urticaria make up a large proportion of the referrals to allergy clinics. There are many causes of urticaria and it is the clinical history which is most important when attempting to identify potential causes; however, urticaria is very often idiopathic. In a small minority of patients urticaria may be a symptom of a serious underlying medical illness or the allergic symptoms may progress to cause systemic reactions, and it is important to identify these patients and to remember that severe urticaria is a distressing and disabling condition. This review will discuss classification, investigation and treatment of urticaria and will consider some of the more unusual types of urticaria that may be encountered in the out-patient clinic.

Antigen presentation by epithelial cells induces anergic immunoregulatory CD45RO+ T cells and deletion of CD45RA+ T cells.

The immunoregulatory effects of alloantigen presentation by tissue parenchymal cells to resting peripheral blood CD4+ T cells was investigated. Coculture of CD45RO+ (memory) and CD45RA+ (naive) T lymphocytes with primary cultures of MHC class II-expressing epithelial cells rendered both populations of T cells hyporesponsive to a subsequent challenge by the same MHC molecule expressed on EBV-transformed lymphoblastoid B cell lines. However, the mechanisms responsible for the allospecific hyporesponsiveness were distinct. For the CD45RO+ T cells, responsiveness was restored by subsequent culture in the presence of IL-2; the addition of IL-2 had no effect on the reactivity of the CD45RA+ T cells. In contrast, the naive T cells were protected from the induction of nonresponsiveness by the presence of a neutralizing anti-CD95 Ab during the culture with thyroid follicular cells. In addition, the hyporesponsive CD45RO+ T cells effected linked suppression, in that they inhibited proliferation against a third-party DR alloantigen when the third-party alloantigen was coexpressed with the DR Ag against which hyporesponsiveness had been induced. These results suggest that recognition of Ag by T cells on tissue parenchymal cells plays an important role in the maintenance of peripheral T cell tolerance, inducing nonresponsiveness in naive and memory T cells by distinct mechanisms.

Adult onset immunodeficiency caused by inherited adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency is identified here as a cause of adult onset immunodeficiency. Two sisters who noted recurrent, predominantly chest infections in their twenties were found in their thirties to have CD4+ lymphopenia and lymphocyte ADA activity of approximately 5% of the lower limit of normal. Immune function, measured by proliferation of PBMCs in vitro to mitogens and specific Ags, was impaired. Inheritance of a polymorphic marker showed that both patients were heterozygous at the ADA locus. In the paternal allele there was a deletion resulting from homologous recombination between two alu elements that normally flank the first exon and the polymorphic marker. The recombination site was distinct from that in similar deletions described in two infants having severe combined immunodeficiency. This allele is predicted to result in a null phenotype. In the mutant allele inherited from the mother, a C to T transition in a CpG dinucleotide changed the codon for arginine 211, which lies in a conserved sequence close to the active site, to that for cysteine. This mutation has been observed previously in a child in whom the other allele was also a null mutation, but who was diagnosed as having partial ADA deficiency because immune function was apparently normal. The late onset of immunodeficiency in our patients suggests that immune function in children with partial ADA deficiency may deteriorate with time and that ADA deficiency should be regarded as a possible cause of adult onset immune dysfunction of unknown etiology.

Positive correlation of T cell sensitization with frequencies of alloreactive T helper cells in chronic renal failure patients.

Chronic renal failure patients are often "sensitized" to foreign alloantigens following renal transplantation or blood transfusion. B cell sensitization is assessed by measuring the reactivity of cytotoxic antibodies in the patient's serum against a panel of allogeneic cells (panel-reactive antibodies, [PRA]). However, this technique provides no information about T cell allosensitization. T cell allosensitization may be important since T cells play a central role in allograft rejection and since "primed" alloreactive cells--i.e., T cells that have previously encountered their specific alloantigen, are relatively resistant to immunosuppression. In order to detect T cell sensitization we used a limiting dilution analysis assay, which measured both total and primed frequencies of alloreactive T helper (Th) cells. Total alloreactive Th cell frequencies were generally high. Primed alloreactive Th cell frequencies could be detected in all patients studied, although there was considerable variation in frequencies between different patients. Frequencies of primed Th cells did not correlate with levels of PRA. However, in all three of the patients who had received DR-mismatched kidneys, and who had subsequently rejected these grafts rapidly, high primed frequencies were detected against the mismatched DR antigens. This was not the case for two patients who had lost their grafts two or more years after transplantation.

Evidence that umbilical cord blood contains a higher frequency of HLA class II-specific alloreactive T cells than adult peripheral blood. A limiting dilution analysis.

Umbilical cord blood has been used to effect hematological reconstitution and there are sufficient stem cells available in the cord blood obtainable from a single placenta to reconstitute an adult patient. Umbilical cord blood might therefore, have widespread potential use in the field of bone marrow transplantation. We compared alloreactivity of paired samples of adult and cord peripheral blood mononuclear cells, by measuring frequencies of both alloreactive T helper cells and cytotoxic T cell precursors (CTLp), using limiting dilution analysis. In addition we compared the phenotype of adult and neonatal PBMC, using monoclonal antibody staining. Cord PBMC in general showed higher frequencies of alloreactive Th than adult PBMC, with statistically significant differences in 6 out of 10 experiments. There was no statistically significant difference between adult and cord CTLp frequencies. Adult and cord PBMC surface phenotype was similar, except that cord blood contained fewer lymphocyte function-associated-3 (LFA-3) positive (memory) cells.

A case of synchronous bilateral separate primary male breast carcinomas.

Breast carcinoma in the male is uncommon, but to find a case of bilateral synchronous primary separate carcinomas is extremely rare. We report on the management of such a case, illustrating current concepts in therapy. This case highlights the fact that, as in the female, bilateral breast carcinomas can occur in the male and the attending surgeon should remain vigilant at all times when treating unilateral disease.

The effects of theophylline and salbutamol on right and left ventricular function in chronic bronchitis and emphysema.

We have compared the effects of oral theophylline and salbutamol on right and left ventricular function in twelve patients with chronic bronchitis and emphysema. Right and left ventricular ejection fraction (RVEF and LVEF) were measured using multiple gated radionuclide ventriculography. Theophylline 600 mg and salbutamol 4 mg both produced increases in RVEF and LVEF. There were no significant changes in blood gases after either drug. The clinical significance of the effects of oral bronchodilators on cardiac function in patients with chronic bronchitis and emphysema has yet to be determined.

Self-administered home intravenous antibiotic therapy in bronchiectasis and adult cystic fibrosis.

10 patients (mean age 23.1, range 17.1-40.5 years), 8 with cystic fibrosis (CF), and 2 with advanced bronchiectasis without CF, were taught, while being treated in hospital for exacerbations of pseudomonas infection, how to continue to give themselves intravenous antibiotics at home. They were discharged after satisfactory antibiotic levels had been achieved, and 22 courses were given at home over a total of 116 patient-days. In 14 of these, the greater part of the course was given at home (mean duration 6.6, range 5-10 days); 2 of these were given without admission to hospital. In the 8 patients with two or more infective exacerbations within a 12-month period there was no difference between home and hospital treatments in clinical improvement or in relapse time, defined as the interval between completion of treatment and subsequent antibiotic therapy. Self-administration of antibiotics intravenously at home for selected adults with cystic fibrosis and severe bronchiectasis reduces hospital stay and does not seem to be associated with an increased rate of recurrent infection.

The role of adherence in determining the site of infection by Corynebacterium diphtheriae.

Twenty-nine strains of Corynebacterium diphtheriae isolated from throats and 29 strains from skin lesions, the latter mainly from communities of low socio-economic status in tropics and cold climates, have been examined for the property of adherence to human buccal epithelial cells. All throat strains showed adherence. In contrast, strains from skin lesions were predominantly poor adherers. These results indicate that strains of C. diptheriae from throats must now be added to the important group of pathogens which possess the property of adherence to surface epithelial cells of mucous membranes, thus providing an essential first step in the process of colonizing their hosts. The possible role of this phenomenon of adherence to bucco-pharyngeal epithelial cells in the evolution of the host-parasite relationship of C. diphtheriae is discussed.