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Biomedical subjects

G P Spickett

Publications and source records attributed to G P Spickett.

18 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

A case of candidal umbilical granuloma.

A case is reported of a 14-year-old boy with a mass arising from the umbilicus, which was a large, well-organized candidal granuloma. Cell markers showed normal numbers and distribution of peripheral T and B lymphocytes but there was no reaction to intradermal injection of Candida, suggesting a specific T-cell defect such as occurs in chronic mucocutaneous candidiasis.

Adolescent↗
PubMed1991

Raised serum levels of CD8, CD25 and beta 2-microglobulin in common variable immunodeficiency.

Soluble CD8, soluble CD4, soluble CD25 (IL-2 receptor), beta 2-microglobulin and the cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in sera from patients with common variable immunodeficiency (CVI). Levels of soluble CD8, soluble CD25 and beta 2-microglobulin but not of soluble CD4 and TNF-alpha were raised significantly above levels in normal sera. Sera from patients with X-linked agammaglobulinaemia, who are also antibody deficient, did not show this marked elevation. The raised levels of soluble CD8, soluble CD25 and beta 2-microglobulin in CVI, correlated with the extent of the defects in the B lymphocytes assessed in vitro, as well as with the clinical severity of the disease. The selective release of these molecules into sera may indicate that abnormal cellular activation occurs in most CVI patients. It is also possible that the raised levels of these soluble molecules play a part in the immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Cellular abnormalities in common variable immunodeficiency.

In most patients with common variable immunodeficiency (CVI) there is evidence for an intrinsic B cell defect, despite an apparently normal cell phenotype. There are at least five separate subgroups of CVI, based on B cell function. These groups may be variations in severity of a single defect, or distinct molecular defects. At least some patients may have an abnormality in the secretory process of the B cell. The existence of patients whose cells can secrete IgM and IgG in vitro and yet are hypogammaglobulinaemic in vivo implies that the architecture of lymphoid organs or the traffic of lymphoid cells may be involved in the pathogenesis of the disease. The data on T cell defects in CVI indicates that, with sensitive assays, many patients have some abnormality. In the face of a much more defined B cell defect it is not yet possible to assess the overall contribution of the T cell defects to the immune failure.

Agammaglobulinemia↗
PubMed1989

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.

Agammaglobulinemia↗
PubMed1989

Thrombophlebitis migrans following co-trimoxazole therapy.

We report an unusual and severe vasculitic disorder following co-trimoxazole, given orally for a urinary tract infection. The vasculitis was manifest solely as thrombophlebitis migrans and involving only veins without evidence of polyarteritis nodosa, or underlying malignancy.

Anti-Infective Agents, Urinary↗
PubMed1989

Defective DNA synthesis by T cells in acquired 'common-variable' hypogammaglobulinaemia on stimulation with mitogens.

We have studied T cell defects in acquired 'common-variable' hypogammaglobulinaemia (CVH) by measuring the synthesis of DNA, RNA and protein in vitro in response to mitogens and to interleukin 2 (IL-2). We have confirmed that some patients have defective DNA synthesis in response to PHA and shown that this extends to responses to cell-derived B cell growth factor (c-BCGF) which is also mitogenic to T cells. DNA synthesis induced by IL-2 was not defective in these patients suggesting IL2-receptor induction is normal. The mitogen-related defect in DNA synthesis was not accompanied by any reduction in synthesis of RNA or of protein. Levels of the rate limiting enzyme (thymidylate synthetase EC 2.1.1.45) responsible for de novo DNA synthesis in the absence of endogenous thymidine were measured following PHA stimulation and found to be in the normal range. In the CVH patients (but not in normal individuals) the relationship between the levels of thymidylate synthetase and DNA synthesis in response to PHA approached significance, suggesting that this pathway becomes more important in CVH patients than in normal individuals perhaps because of defects in the thymidine 'salvage' pathway.

Agammaglobulinemia↗
PubMed1989

Accessory and T cell defects in acquired and inherited hypogammaglobulinaemia.

Cellular defects in patients with common variable hypogammaglobulinaemia (CVH) and X-linked agammaglobulinaemia (XLA) have been studied in vitro, using a mitogen-driven system of immunoglobulin production. We have confirmed our previous finding of impaired low-density (dendritic) accessory cell function in CVH and now show that accessory cell function is normal in XLA. We demonstrate that macrophage accessory function is normal in CVH. T cell help for IgM production is also deficient in CVH, and T cell help in XLA is also abnormal for both IgG and IgM. Some XLA patients have excessive T suppressor activity. The contribution of these defects to the clinical states is discussed.

Agammaglobulinemia↗
PubMed1988

Viruses and antibody deficiency syndromes.

Viral infections that occur in patients with primary immunodeficiencies are summarized. These viral infections include: Echovirus, poliovirus, varicella zoster, non-A non-B hepatitis and hepatitis B. Cases of X-linked lymphoproliferative syndrome associated with Epstein-Barr virus infection and congenital rubella syndrome are also reviewed. In the second part of the paper, retrovirus (HIV) isolations from blood mononuclear cells of 3 out of 31 patients with common variable hypogammaglobulinemia are reported. This supports the concept that some of the non-familial "primary" immunodeficiencies may be due to retrovirus infections.

Agammaglobulinemia↗
PubMed1988

Role of retroviruses in acquired hypogammaglobulinaemia.

Mononuclear cells were obtained from 42 patients with 'common variable' hypogammaglobulinaemia (CVH) and co-cultured with various cell lines in an attempt to isolate retroviruses. Cultures from only two patients showed evidence of a viral infection, although the virus could not be isolated and characterized in either. Despite the previous isolation of HIV's from two other CVH patients, this data suggests that similar viruses are not etiologically involved in the majority of patients.

Adult↗
PubMed1987

Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient.

In many endoscopy units midazolam is replacing diazepam as the intravenous sedative of first choice. Midazolam is approximately twice as potent as diazepam. Although generally considered a safe drug, there have been a number of recent reports, particularly in the elderly, of the drug causing hypotension, respiratory depression and even death. There have been at least ten studies comparing diazepam with midazolam for upper gastrointestinal endoscopy but many have involved relatively small numbers and none have adequately addressed the question of dosage in the elderly. We have carefully recorded the dose of intravenous midazolam used to produce adequate sedation prior to upper gastrointestinal endoscopy in 800 consecutive patients. The dose of midazolam decreased markedly with age in both male and female patients. There was a highly significant correlation in both sexes between age and the dose of midazolam (rho -0.787, P less than 0.001 for males and rho -0.768, P less than 0.001 for females). There was only a small difference in dose in men and women, an average of 1 mg; and no difference in dose over the age of 70 years. In patients over 70 years of age the dose of midazolam necessary for endoscopy is often so small that overdosage is all too easy.

Adolescent↗