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Biomedical subjects

H M Chapel

Publications and source records attributed to H M Chapel.

At least 19 recordsLinked to original sources

A comparison of specific IgG antibody levels to the cell wall mannan of Candida albicans in normal individuals and in patients with primary antibody deficiency.

An enzyme-linked immunosorbent assay (ELISA) has been developed to measure specific IgG antibody to the polysaccharide, cell wall mannan of Candida albicans (mannan). The results were expressed as arbitrary units/ml, with an inter- and intra-assay coefficient of variation of 7-11%. In establishing normal ranges we found that specific IgG to the mannan increased with age, with 18% of healthy children aged 3-10, 48% of healthy children aged 11-19 and 76% of an adult donor population having specific IgG antibody to mannan (greater than 30 U/ml). We have compared these normal ranges, with a group of patients with primary antibody deficiency (PAD). None of the 23 patients with PAD, which included common variable immunodeficiency, IgG subclass deficiency, and selective IgA deficiency, had titres greater than 30 U/ml. The patients with PAD had significantly lower levels of specific IgG anti-mannan antibody (median 9 U/ml) compared to healthy children aged 11-19 (median 26 U/ml) or adults (median 58 U/ml) (p = less than 0.001) but not children aged 3-10, (median 1 U/ml) (p = 0.08).

Adolescent

Immunogenicity of combined diphtheria, tetanus, and pertussis vaccine given at 2, 3, and 4 months versus 3, 5, and 9 months of age.

In the UK an accelerated schedule for immunisation against diphtheria, tetanus, and pertussis (injections at 2, 3, and 4 months of age) was introduced in 1990 to replace the more widely spaced schedule of 3, 5, and 9 months. There is concern, however, that the new schedule may be less immunogenic and therefore less protective than the old schedule. We have measured serum concentrations of antibodies against diphtheria, pertussis, and tetanus in infants immunised according to the two regimens. Both schedules resulted in protective concentrations of antibody against tetanus and diphtheria and in satisfactory antibody responses to three pertussis antigens (filamentous haemagglutinin, pertussis toxin, fimbriae). However, immunisation by the old schedule led to significantly higher antibody concentrations against both diphtheria and tetanus than did immunisation by the new schedule (p less than 0.01). In infants immunised with the new schedule, postimmunisation antibody concentrations against tetanus toxoid and against two pertussis antigens (pertussis toxin and fimbriae) were significantly lower in infants in whom preimmunisation (maternally derived) antibody concentrations were high (p less than 0.02). The findings suggest that with an accelerated immunisation schedule maternal antibodies can have an inhibitory effect on the responses to immunisation against tetanus and pertussis.

Antibodies, Bacterial

Chronic enteroviral meningoencephalitis in agammaglobulinemia: case report and literature review.

Chronic enteroviral meningoencephalitis is a well-recognized complication in patients with X-linked agammaglobulinemia (XLA). The majority of published cases refers to its occurrence in patients on no replacement therapy or on only intramuscular immunoglobulin. The advent of intravenous immunoglobulin (IVIg) in the early 1980s and its widespread use in XLA was thought to have virtually eradicated enteroviral meningoencephalitis in these patients. We describe the development of echovirus meningoencephalitis in an 11-year-old boy on regular IVIg replacement whose serum IgG levels were maintained at between 6 and 8 g/L (NR 6-13 g/L). Treatment with daily high-dose IVIg was commenced, with significant clinical improvement being noted within a few weeks in association with a reduction in blood-brain barrier permeability. The persistence of live virus, however, necessitated the use of intraventricular immunoglobulin. The virus proved resistant to two courses of specific intraventricular immunoglobulin and a 6-week course of oral ribavirin and eventually proved fatal 5 months after presentation. In view of the therapeutic uncertainties we have reviewed the use of immunoglobulin in the treatment of enteroviral meningoencephalitis over the past 6 years.

Acyclovir

Immunoglobulin replacement in patients with chronic lymphocytic leukemia (CLL): kinetics of immunoglobulin metabolism.

Fifteen patients with low-grade B-cell tumours were given 3-weekly infusions for 1 year of intravenous immunoglobulin (IVIg) at a dose of 0.4 g/kg. Serial measurements of serum IgG levels were made; analysis of eight samples taken at intervals after the end of the last (17th) infusion showed that the half-life of IgG in such patients was no shorter than in normal individuals. To look at the average rates of catabolism of IgG during the year serum IgG was measured at four time points (pre, post, day 7, and day 21) after the 5th, 8th, 13th, and 17th infusions; these data showed that there were no changes in catabolism. Finally, there was a significant correlation (P less than 0.005) between the pretreatment serum IgG level and the increase to the mean trough level achieved after the fifth and subsequent infusions (in each individual). These data suggest that the catabolic rate of IgG is normal in patients with low-grade B-cell tumours and that it is not altered by regular IVIg infusions once a steady state is reached. Significant correlation of the increment of serum IgG with the endogenous synthesis level supports the theory that the IgG half-life is proportional to the IgG level at any given time.

Agammaglobulinemia

Progressive multifocal leucoencephalopathy, sclerosing cholangitis, bronchiectasis and disseminated warts in a patient with primary combined immune deficiency.

A 24 year old man presented with an unusual primary combined immune deficiency syndrome characterised by a profound lymphopenia of CD4 cells, selective serum IgG2 subclass deficiency, poor polysaccharide antibody responses, disseminated warts, recurrent sinopulmonary infection and bronchiectasis. The developed progressive multifocal leucoencephalopathy (PML) in association with sclerosing cholangitis. Progressive multifocal leucoencephalopathy (PML) usually occurs as an opportunistic infection in patients with secondary defects in cellular immunity.

Adult

Prolonged faecal excretion of poliovirus in a nurse with common variable hypogammaglobulinaemia.

A nurse with common variable hypogammaglobulinaemia was found to excrete a non-vaccine strain type II poliovirus for almost a year following a bout of gastroenteritis. Attempts were made to halt intestinal carriage of the virus in view of the possible risk of spread to immunocompromised patients and the risk of paralytic poliomyelitis to the patient himself. Three doses of killed Salk vaccine failed to stimulate salivary anti-polio antibodies. Excretion of the virus ceased spontaneously just before oral immunoglobulin containing high titres of antibodies to polio virus was used to halt virus excretion.

Adolescent

Titration of antibodies against neutrophil cytoplasmic antigens is useful in monitoring disease activity in systemic vasculitides.

Titration of antibodies against neutrophil cytoplasmic antigens (cANCA), as detected by indirect immunofluorescence, is shown to be clinically useful for monitoring disease activity in Wegener's granulomatosis and microscopic polyarteritis. Ten patients were followed (eight from presentation) prospectively for up to 2 years; during this time there were six episodes of vasculitic relapse in four patients and five infective episodes and one pulmonary embolus in four patients. Titres of cANCA were markedly raised, both at presentation (1/32-1/2048) and at vasculitic relapse (1/125-1/1048) but not in infection or embolism (negative, 1/16). Thus the titre of these antibodies can distinguish nonvasculitic illness from vasculitic relapse, in contrast to C-reactive protein levels which were raised in both. Titres of cANCA fell gradually after vasculitic relapse, in keeping with the half-life of IgG (3 weeks). C-reactive protein is a better measure of recovery.

Adult

A study of the aetiology of gastritis following gastric surgery. I. Immunofluorescent studies of the gastric mucosa.

The gastritis which follows surgical trauma is probably not of autoimmune origin. Although identical with the gastritis of pernicious anaemia (PA) upon routine histological examination, immunofluorescent examination of post-operative gastritis differs in that IgA-containing plasma cells alone are found, in contrast to the predominantly IgG-containing plasma cells in PA.

Adult

Combined T and B lymphocyte marker test in lymphoproliferative disorders.

The combined T and B lymphocyte marker test of Mendes et al (1974) has been developed to provide an easy, reproducible test for clinical practice. It has been used to study subpopulations of peripheral lymphocytes in patients with lymphoid malignancies. Significant increases in the numbers of lymphocytes which bind both sheep erythrocytes (E) and the fixed, third component of complement (C3) have been found using this test, in the peripheral blood of all untreated lymphosarcoma (L/SA) patients and T cell acute lymphoblastic leukaemia (ALL) patients. Such increases were not found in blood from patients with chronic lymphatic leukaemia (CLL), other non-lymphoid malignancies, null-cell ALL or normal individuals. These mixed E and C3 receptor bearing cells may be Fc receptor positive and represent a separate subpopulation of lymphocytes.

B-Lymphocytes