The Benzodiazepine Withdrawal Symptom Questionnaire

A self-report questionnaire is described which records the main symptoms experienced during withdrawal from benzodiazepines in pharmacologically dependent patients. The questionnaire consists of 20 items; evidence is given that these are reasonably independent and are sensitive in detecting withdrawal symptoms from a study of 68 patients undergoing slow withdrawal from benzodiazepines.     

Analysis of two IL-4 promoter polymorphisms in a cohort of atopic and asthmatic subjects

The Th2 cytokine interleukin 4 (IL-4) has been identified as having a central role in driving the inflammatory immune responses which are present in atopic airway disease. This study examined the distribution of two putative IL-4 promoter polymorphisms (-285 C-T and -81 A-G) in groups of patients with severe and moderate asthma, non-asthmatic atopy and control subjects. Neither polymorphism was identified in any of the samples tested. The data suggest that either the polymorphisms are present at very low frequencies or are artefacts of the B cell lines from which they were identified.     

Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection

Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.     

Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting

Malaria infection induces the production of serum antibodiesto a variety of malaria antigens but the prevalence of antibodiesto any particular antigen ins typically mucb less than 100%.It has been assumed that non-responsiveness to defined antigensin malaria immune subjects is due to HLA mediated restricutionof the Immune response. In this study we have investigated therole of HLA and non-HLA genes in the antibody response to twomerozoite surface antigens (MSP1 and MSP2) and a sexual stageantigen (Pfs260/230) opf P{lasmodium falcpartum, and concludethat host genotype is not a major determinant of responsiveness.Although antibody levels vary in accordance with seasonal variationsin malaria transmission in semi-immune children, antibiody levelsremain stable in clncall immine adults.     

Evaluation of the use of Bactec anaerobic blood cultures in the detection of bacteraemia and fungaemia in children

In an attempt to reduce costs, the role of Bactec anaerobic blood culture in the detection of bacteraemia and fungaemia in children was evaluated. Results from 3167 sets of aerobic and anaerobic blood cultures from children admitted to the University Hospital, Kuala Lumpur during a one year period, were analysed. Four hundred and eight (12.9%) sets of blood cultures were positive, of which 348 sets (11.0%) from 201 patients were clinically significant. Of the 348 significant positive sets, organisms were isolated on 177 (50.9%) occasions from both aerobic and anaerobic bottles, on 136 (39.1%) occasions from the aerobic bottle only and 35 (10.0%) occasions from the anaerobic bottle only. No strict anaerobes were isolated, but clinically significant isolates recovered from the anaerobic bottle only included Klebsiella pneumoniae, Salmonella species, Enterobacter cloacae, Staphylococcus aureus, coagulase negative staphylococci, Streptococcus pneumoniae and Group B streptococcus. Patients with bacteraemia diagnosed solely by anaerobic culture were distributed evenly across the various paediatric subspecialities. When results from the anaerobic bottles were excluded, the overall isolation rate was reduced from 11% to 9.9%. Potential financial savings resulting from omission of anaerobic cultures must be balanced against the small number of bacteraemic episodes that could be missed. Undiagnosed bacteraemia may result in increased morbidity and mortality with its own attendant financial implications.     

Genetic predetermination of quantitative expression of HLA antigens in platelets and mononuclear leukocytes

In view of the potential functional importance of quantitative expression of HLA antigens, a series of studies were conducted to determine the relative quantities of specific HLA-A and -B antigens expressed in MNLs and platelets of HLA-phenotyped family members and unrelated individuals. An mAb that reacts with a well-defined monomorphic epitope in the α₃ domain of the heavy chains of HLA molecules was developed and used to quantify each HLA-A or -B antigen on western blots of IEF gels. The results of these studies demonstrated that the relative quantities of HLA-A and -B antigens in platelets and MNLs of an individual did not change over time. Further studies showed that the relative quantities of HLA-A and -B antigens for haplotypes shared among the first-degree relatives were always the same and followed Mendelian inheritance. In contrast, the relative quantities of HLA-A and -B antigens for a haplotype shared by unrelated individuals varied significantly. All these findings support the hypothesis that the quantitative expression of HLA antigens is genetically predetermined and may play important roles in determining disease susceptibility and severity. Human Immunology 38, 243–250 (1993)     

Immune response to soluble exoantigens of Plasmodium falciparum may contribute to both pathogenesis and protection in clinical malaria: evidence from a longitudinal, prospective study of semi-immune African children

Some soluble exoantigens of Plasmodium have lipopolysaccharide (LPS)-like properties and are believed to contribute to the pathogenesis of acute malaria. We have studied cellular and humoral immune responses to several purified exoantigens of Plasmodium falciparum in a cohort of children and compared these responses with their subsequent susceptibility to malaria infection and clinical disease. We found no evidence that either lymphoproliferative or interferon-gamma (IFN-gamma) responses to these antigens were associated with protective immunity. On the contrary, children whose cells produced IFN-gamma after in vitro activation with one of the soluble antigens (Ag7) were more likely to experience clinical manifestations of malaria infection (fever and malaise) than were children whose cells did not produce IFN-gamma. It is possible that exoantigen-induced IFN-gamma may exacerbate the LPS-like effects of these antigens. However, serum antibodies to another antigen (Ag2) were more prevalent in children with asymptomatic infections or low parasitemia than in children with fever and higher parasitemia (confirmed clinical malaria), suggesting that these antibodies may contribute to the development of protective immunity.     

Bacteriophages in autoimmune disease and other inflammatory conditions

There are several autoimmune diseases and other inflammatory conditions where an infectious aetiology is suggested by the epidemiology, clinical course and pathological findings. Many candidate bacteria and viruses have been considered as potential aetiological agents but mostly without firm proof. Bacteriophages are viruses that infect bacteria and may be found wherever bacteria are located, but would not be detected unless specifically sought. They have not previously been considered to be pathogens. Bacteriophages are immunogenic and therefore could play a role in the pathogenesis of autoimmune and other inflammatory diseases by acting as antigens on epithelial surfaces, bound to antibody as immune complexes, through molecular mimicry or possibly as superantigens.