Biomedical subjects
Publications and source records attributed to R A Thompson.
The case history is presented of a patient with common variable immunodeficiency in whom heart lung transplantation has been carried out with success. Transplantation was the only long term therapeutic option in this patient due to the progressive respiratory failure resulting from bronchiectasis, emphysema, and granulomatous lung disease.
Serum total immunoglobulin (G, A, M and E) and IgG subclass levels were studied in 23 patients with brittle asthma, 23 age- and sex-matched patients with mild asthma and 33 patients with recurrent infective exacerbations of their asthma. Patients with brittle asthma showed significantly reduced levels of IgG (mean +/- SD, 8.8 +/- 3.3 g l-1) compared to patients with mild asthma (11.0 +/- 2.5 g l-1) (P < 0.008) with further significant reductions in the brittle compared to the mild group in IgG1 (5.2 vs 6.3, P = 0.035), IgG2 (2.4 vs 3.25, P < 0.006), IgG3 (0.39 vs 0.55, P < 0.05) and IgA (1.91 vs 2.38, P < 0.03). There were no significant differences between the brittle group and the group with recurrent infective exacerbations for any parameter, but the latter group showed significantly reduced levels of IgG (8.2, P < 0.001), IgG1 (4.9, P < 0.00001) and IgG2 (2.5, P < 0.02) compared to the mild group. In all groups, there was no relationship between dose of inhaled steroids and levels of any antibody. These findings suggest that the presence of a mild degree of humoral immunodeficiency relates to severity of asthma, and suggests that immunoglobulin replacement therapy may be appropriate in patients with the more severe forms of asthma.
The killing of Candida albicans by a series of amphiphilic quaternary ammonium compounds (QACs) with different hydrocarbon chain lengths was closely related to the binding of the compounds to the cells and damage of the cell membranes. The membrane damage was measured as the level of release of the UV-absorbing material into the medium in which the cells were suspended and as the level of uptake of propidium iodide in individual cells by flow cytometry. It was shown that of the compounds tested, hexadecyltrimethylammonium bromide (cetyltrimethylammonium bromide [CTAB]) bound most efficiently. Tetradecyl betainate chloride (B14), tetradecanoylcholine bromide (C14), tetradecyltrimethylammonium bromide (TTAB), and dodecyltrimethylammonium bromide (DTAB) followed and had declining degrees of binding efficiency. The proportion of CTAB bound was almost total at concentrations up to the critical micelle concentration (CMC) of the compound, whereas that of B14 was somewhat smaller. For the two remaining tetradecyl compounds (C14 and TTAB), still smaller proportions were bound at low concentrations, but the proportions rose disproportionally at increasing concentrations to a distinct maximum at concentrations of 0.2 to 0.5 times the CMC. We propose that interfacial micelle-like aggregates are formed at the cell surface as a step in the binding process. An analogous, but less conspicuous, maximum was seen for DTAB. Thus, great differences in the binding affinity of QACs with different hydrocarbon chains at different concentrations to C. albicans were observed. These differences were related to the CMC of the compound. In contrast, the binding of TTAB to Salmonella typhimurium 395 MS was almost total at low as well as high concentrations until saturation was attained, indicating fundamental differences between binding to the yeast and binding to gram-negative bacteria. The importance of lipid-type complexes or aggregates to the antifungal effect of membrane-active substances are discussed.
X-linked hyper-IgM syndrome (X-HIM) is an immunodeficiency caused by mutations in the gene encoding the CD40 ligand (CD40L). A database (CD40Lbase) of CD40L mutations has now been established, and the resultant information, together with other mutations reported elsewhere in the literature, is presented here.
Myasthenia gravis is probably commoner than previously suspected, the annual incidence being nearer 9-10/million than earlier figures of 2-4/million. The current study found an annual incidence in Croyden of 9.1 per million (95% confidence limits 5.7-13.8 per million). Of the 22 patients (59%) seen in Croyden with newly diagnosed myasthenia gravis during the past 7 years, 13 were aged over 60. In a separate study of the age distribution of positive acetylcholine receptor antibody assays, 51% were 60 years or above in 1991, and 64% in 1994. The peak age in both sexes was 70-80, and numbers were greatest in men aged 60-80.
The relation between adult perception of emotion intensity in the cries of 1- and 6-month-old infants and the acoustic characteristics of the cries was examined. In the first study, adults who were inexperienced in child care rated 40 cries on 3 emotion intensity scales: anger, fear, and distress. The cries of 6-month-olds were rated as being significantly more intense. Different acoustic variables accounted for emotion intensity ratings for the 2 infant ages. Peak amplitude and noisiness of the cry predicted adult judgments of intensity ratings of 1-month-olds' cries; a measure of amplitude ratio (in 2 frequency bands) was the best predictor of intensity ratings of 6-month-olds' cries. In the second study, parents of infants rated the same cries on the same scales. They also rated the older infants' cries as being more intense. The 2 adult groups did not differ on their ratings, and a regression equation derived from one adult group predicted the other adult group's rating of the same infant age better than it predicted its own ratings for the other infant age. Infant age, and its associated acoustic features, seems to be a more important determinant of adults' perception of emotion intensity than are such adult characteristics as gender or infant-care experience.
The recent history of federal support for child maltreatment research paints a mixed picture of inadequate funding and uncertain administrative guidance against a backdrop of growing public concern about the prevalence of child abuse and neglect. This article describes some of the problems that have been identified in federal research funding, administration, and support of research initiatives and training concerning child abuse and neglect. Remedies for these difficulties are outlined, priorities for new research in this area are identified, and ways in which to rejuvenate the federal government's role in this area, in league with a concerted commitment to policy-relevant research by behavioral scientists, are suggested.
A new category of amphiphilic hydrolyzable quaternary ammonium compounds with rapid and high levels of antimicrobial activity was studied. The compounds, alkanoylcholines with hydrocarbon chains of 10 to 14 carbon atoms, are hydrolyzed by butyrylcholine esterase, which is present in human serum and mucosal membranes. The hydrolysis products are common components of human metabolism. Alkanoylcholines were tested and found to be active against gram-negative and gram-positive bacteria as well as yeasts. The microbicidal activities of the alkanoylcholines were comparable to the activities of the stable quaternary ammonium compounds of corresponding chain length and increased with an increasing number of carbon atoms. The compounds were also found to be hydrolyzed by enzymes present in certain microorganisms. The degradation was achieved after reaching the microbicidal effect.
BACKGROUND: The hydrolysis of long-chain alkanoylcholines, presumably catalyzed by butyryl-cholinesterase (EC 3.1.1.8), in rat intestinal loops was studied. The substances have earlier been found to be rapidly degraded in vitro. METHODS: Radiolabeled substrates were used, and a radiochromatographic detection method was applied. RESULTS AND CONCLUSION: The long-chain alkanoylcholines were rapidly hydrolyzed. The rates of the reaction and the chain-length dependence were similar to those reported earlier in vitro. At high substrate concentrations the hydrolysis reaction was inhibited. This could be due to conformational changes of the enzyme, caused by the adsorption of the cationic amphiphile, or to a decrease in the free substrate concentration after incorporation of the amphiphilic ester into the lipid layer of the cell membranes. The enzymatic activity towards the substrates in different parts of the rat intestinal tract was also studied and found to be highest in the duodenum.
Fathers figure prominently in a child's postdivorce life whether they are involved or disinterested, but concerns about inadequate child support, noncustodial fathers who fail to visit, and the economic plight of single mothers have together raised policy questions about how better to enfranchise fathers with the rights and responsibilities of parenting and ensure them a continuing and meaningful role in the lives of their offspring. This article focuses on obstacles and avenues to ensuring a meaningful postdivorce parenting role for fathers by examining the effects on them of custody standards, visitation policies, child support guidelines and their enforcement, and the other economic arrangements surrounding contemporary divorce. In the end, public policies that foster the child's unconflicted relationships with each parent in the context of reliable and adequate economic support will require new ways of structuring relations between ex-spouses in the interests of offspring (for example, new approaches to custody and visitation), nonadversarial modes of assisted dispute resolution to accommodate postdivorce changes in family life, child support policies which guarantee that a child's economic needs will be met when parents are unable to provide adequately (and that assist parents who are unable to provide), and that recognize and ensure both the relational and the economic contributions of each parent to a child's well-being.
Contemporary interest in emotion regulation promises to advance important new views of emotional development as well as offering applications to developmental psychopathology, but these potential contributions are contingent on developmentalists' attention to some basic definitional issues. This essay offers a perspective on these issues by considering how emotion regulation should be defined, the various components of the management of emotion, how emotion regulation strategies fit into the dynamics of social interaction, and how individual differences in emotion regulation should be conceptualized and measured. In the end, it seems clear that emotion regulation is a conceptual rubric for a remarkable range of developmental processes, each of which may have its own catalysts and control processes. Likewise, individual differences in emotion regulation skills likely have multifaceted origins and are also related in complex ways to the person's emotional goals and the immediate demands of the situation. Assessment approaches that focus on the dynamics of emotion are well suited to elucidating these complex developmental and individual differences. In sum, a challenging research agenda awaits those who enter this promising field of study.
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Sera from patients with a vasculitis and controls were investigated for the presence of anti-endothelial cell antibodies(AECA), anti- neutrophil cytoplasmic antibodies(ANCA) and anti-myeloperoxidase (MPO) antibodies. Only 19% of patients with Wegener's granulomatosis and 2% of patients with microscopic polyarteritis had AECA. Our data suggests that AECA are a minor antibody system in vasculitis.
Superficial transitional cell carcinoma of the bladder is associated with a 15 to 70% recurrence rate within 2 years. Most recurrences are superficial. A recurrence after 2 disease-free years is unusual. A review of the tumor registry revealed 124 patients followed for superficial disease at the Veterans Administration Center in Baltimore. Of the patients 20 were identified with either stage Ta (7) or stage T1 (13) papillary transitional cell carcinoma who had completed at least 5 years of surveillance without tumor recurrence. Invasive transitional cell carcinoma of the bladder requiring cystectomy developed in 7 of these 20 patients after remaining tumor-free for 5 years (stage Ta in 4 and stage T1 in 3). All 7 patients had organ-confined disease and were alive with no evidence of disease at 18 months to 5 years after cystectomy. These results demonstrate that superficial, low grade transitional cell carcinoma of the bladder can become muscle invasive despite careful surveillance and a long dormant period. In our series yearly cystoscopy and urine cytology identified tumor recurrence before metastases developed, suggesting that long-term surveillance is required in patients with superficial bladder cancer.
Thirteen patients suffering from primary hypogammaglobulinaemia receiving intravenous immunoglobulin replacement therapy underwent computerized tomography of the paranasal sinuses. The CT scans were evaluated and related to clinical data from the patients, who were selected for study on the basis of having symptoms of rhinosinusitis. The scans varied from normal to demonstrating widespread sinus abnormality. There was no relationship between the scan findings and duration of ENT symptoms, range of current symptoms, or the interval between the onset of ENT symptoms and the start of intravenous immunoglobulin replacement therapy. It is nevertheless possible that prompt institution of replacement therapy, after correct diagnosis early in the course of the disease, may prevent the development of sinus disease refractory to such treatment.
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AIMS: To make a preliminary assessment of the clinical relevance of serum vitronectin concentrations in various disease groups, using a recently available commercial radial immunodiffusion kit. METHODS: Serum vitronectin concentrations were measured in 80 control subjects and 144 patients with various diseases. The following characteristics were used to evaluate the test procedures: linearity of method, inter- and intrabatch precision, effect of storage, temperature and in vitro activation of the classical and alternative complement pathways on vitronectin concentrations. RESULTS: Significantly reduced serum vitronectin concentrations were found in patients with liver disease, renal disease, and systemic lupus erythematosus (SLE) (normal C3 and C4 concentrations, when compared with normal subjects. This particular method was suitable for measuring vitronectin concentrations in serum samples provided they were stored at -20 degrees C. CONCLUSIONS: The clinical value of measuring serum vitronectin seems to be limited, but a larger study may be justified to ascertain the clinical importance of reduced serum vitronectin concentrations in liver diseases, and the possible role of vitronectin in other disease processes.
We studied sera from patients with vasculitis and controls for the presence of anti-endothelial cell antibodies (AECA) and correlated these with disease type, anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase (MPO) antibodies. AECA were detected by a cellular ELISA on cultured human umbilical vein endothelium. AECA were found in the sera of one of 43 patients with microscopic polyarteritis (2%), five of 27 patients with Wegener's granulomatosis (19%), three of 23 patients with an idiopathic glomerulonephritis (13%), none of eight patients with rheumatoid arthritis and three of 12 patients with rheumatoid vasculitis (25%). In patients with a vasculitis AECA titres were higher in sera with a positive ANCA as compared with ANCA negative sera although the difference was not significant (P = 0.0702) and there was no correlation between AECA and anti-MPO titres (r = 0.1171 P = 0.114). AECA binding was not enhanced following upregulation of endothelial ICAM-1 and ELAM-1 by TNF alpha. This study shows that AECA occur infrequently in microscopic polyarteritis and Wegener's granulomatosis, and are not a major antibody system in these vasculitides.