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Biomedical subjects

R A Thompson

Publications and source records attributed to R A Thompson.

At least 73 records · Page 4Linked to original sources

Evaluation of an enzyme immunoassay for total IgE on a semi-automated analyser. A multicentre study.

Total serum IgE was measured by a semi-automated enzyme immunoassay on sera from normal and disease groups. Data from this investigation was analyzed in respect of precision, linearity, sensitivity and correlation with other test methods. Using human serum pools having values between 7 and 480 IU/ml, the intra-assay coefficient of variation ranged from 3.3 to 14.6% with an arithmetic mean of 6%. The inter-assay coefficient of variation on commercially supplied control sera ranged from 4.4 to 14.2%. In addition, tests were carried out on serially diluted samples to assess the linearity of the method, and on sera with IgE levels of less than 5 IU/ml in order to assess its sensitivity. It was shown that the technique being assessed was unaffected by the presence of lipid or haemoglobin or by the addition of bilirubin or any one of 46 commonly prescribed drugs each at double its toxic dose. There was good correlation between the semi-automated enzyme immunoassay technique and four other methods used during this study. This technique exhibits excellent specificity, reproducibility and a sensitivity well within clinical demands.

Antibodies, Anti-Idiotypic↗

Chromosomal aberrations in the cotton rat, Sigmodon hispidus, exposed to hazardous waste.

The study of chromosome damage in rodents living on hazardous-waste sites may provide evidence of important biological consequences of chronic exposure to toxic chemical wastes. This study compared bone-marrow cells of animals (Sigmodon hispidus) taken from two superfund waste-disposal sites with those from an uncontaminated site and demonstrated that both populations exposed to hazardous wastes had significantly more structural and numerical aberrations than the control population.

Animals↗

Immunodeficiency due to defects of polymorphonuclear leukocyte function.

Functional defects of polymorphonuclear leukocytes can lead to clinical immunodeficiency. Understanding these conditions requires a knowledge of normal polymorph physiology and the means to analyse various aspects of polymorph function. Primary diseases of polymorph function are rare, whereas disorders secondary to other diseases are more common. Prompt diagnosis of these conditions leads to better patient management.

Cell Movement↗

Temperament, emotion, and social interactive behavior in the strange situation: a component process analysis of attachment system functioning.

This study examines the contributions of temperamentally and nontemperamentally based emotional reactions to the organization of social interactive behavior within the Strange Situation to better understand the emotional underpinnings of attachment system functioning. At 12 1/2 and 19 1/2 months, temperamental fear (assessed via maternal report) was related to independent per-episode dimensions of social interactive and distress behavior. Fear was moderately correlated with both distress and interactive dimensions at each age. Path-analytic models revealed that temperamental fear had direct effects on interactive behavior and also indirect effects mediated by preceding distress reactions. However, residualized measures of "context-specific" distress (with temperamental variance removed) were still highly consistent across Strange Situation episodes and also significantly predicted subsequent social interactive behavior; furthermore, stable distress reactions from 12 1/2 to 19 1/2 months significantly predicted concurrent stability in social interactive behavior. We discuss likely sources of "context-specific" emotional influences on Strange Situation behavior and also age-related differences in these findings.

Affective Symptoms↗

Insulin receptor antibodies in diabetes mellitus.

Sera from 80 subjects with IDDM and NIDDM, together with sera from 20 patients with miscellaneous autoimmune conditions and 20 healthy adult subjects were tested for insulin receptor antibodies by (1) inhibition of 125I-insulin binding to EBV-transformed lymphoid cells, and by (2) immunoprecipitation of solubilized insulin receptors in the presence of an excess of mono-specific anti-human IgG or IgM; this test allowed the assessment of the class of antibody activity. Anti-insulin antibodies in the sera were also measured using a double antibody technique. Anti-insulin receptor antibodies were found in 13 of 33 subjects with IDDM and six of 47 with NIDDM. These were principally in the IgM class, and in both groups of diabetics there was a good correlation between % inhibition of insulin binding to intact cells, and % of antibody precipitated by IgM (P less than 0.001), but not by IgG (P greater than 0.1). There was also a good correlation between the % inhibition of insulin binding to intact cells and the daily dose of insulin used in treatment (P less than 0.001). Insulin antibodies were found in seven of 33 subjects with IDDM and six of 12 with NIDDM, all of whom were on insulin treatment. These six subjects were the only ones with NIDDM who also had anti-insulin receptor antibody activity, suggesting that such antibodies may represent auto-anti-idiotype activity. This study shows that autoimmunity in insulin dependent (Type I) diabetes is not limited to islet cells and that such patients also develop antibodies to the insulin receptor. While three out of five patients with relative insulin resistance (requirement greater than 90 u/day) also showed evidence of insulin receptor antibody activity, the clinical significance of these antibodies has yet to be determined.

Adolescent↗

Primary hypogammaglobulinaemia and arthritis.

Arthritis may be the first clinical manifestation of primary hypogammaglobulinaemia. In 16 years of 281 patients who had immunodeficiency, 30 had arthritis at presentation. It was more common in Bruton's disease (15 (22%) of 69 patients) than in other forms of immunodeficiency (15 (7%) of 212 patients). Non-septic arthritis was more prevalent than septic arthritis, particularly monoarticular arthritis in Bruton's disease and pauciarticular disease in common variable immunodeficiency. Boys in whom a diagnosis of Bruton's disease was delayed were likely to develop recurrent infections complicated by arthritis. The measurement of serum immunoglobulin concentrations readily differentiates immunodeficiency from conditions such as Still's disease and dictates subsequent management.

Agammaglobulinemia↗

A comparison of the cerebral protective effects of isoflurane and barbiturates during temporary focal ischemia in primates.

Isoflurane has protective properties during experimental global brain ischemia or hypoxia. However, this has not been evaluated in the more common case of focal ischemia, e.g., as caused by middle cerebral artery occlusion (MCAO). The authors therefore compared the effects of isoflurane, thiopental, and N2O/fentanyl anesthesia on neurologic and neuropathologic outcome in baboons subjected to 6 h of transorbital left MCAO. Prior to MCAO, animals were assigned to one of three groups: Group 1 (n = 7) received isoflurane (in O2/air) in concentrations sufficient to maintain deep burst suppression on the EEG (2.0% +/- 0.5% inspired, mean +/- SD); group 2 (n = 6) received thiopental (O2/air) in doses adequate to maintain similar EEG suppression (3.6 +/- 0.7 g total); and group 3 (n = 6) received 60% N2O/40% O2 and fentanyl (25 micrograms/kg load, 3 micrograms X kg-1 X h-1 infusion). Efforts were made to keep mean arterial pressure (MABP) between approximately 80 and 100 mmHg, using nitroprusside/hydralazine or phenylephrine/metaraminol, with PaCO2 at approximately 30 mmHg. The selected anesthetic was established 45 min before MCAO, was maintained until 1 h after clip removal, and in decreasing concentrations for 5 h. Neurologic status was scored for 7 days and formalin-fixed brains were later sectioned for determination of infarction volume. Six of seven group 1 (isoflurane) animals were hemiplegic, and 7/7 had verified infarctions. By contrast, 4 of 6 group 2 (thiopental) animals were normal, with 2/6 having infarctions. Outcome in group 3 (N2O/fentanyl) was intermediate between groups 1 and 2 (3/6 hemiplegic, 4/6 with infarctions). Differences in the infarction rates between groups 1 and 2 was significant (P less than 0.05), while a similar comparison of neurologic outcome scores achieved a P value of 0.055. Infarctions in group 1 were more hemorrhagic in character than in group 3 (groups 1 and 2 could not be meaningfully compared). These results must be considered in light of differences in MABP during the occlusion period; MABP in group 1 was approximately 80 mm Hg in spite of vasopressor use, while that in group 2 was approximately 100 mmHg (in spite of vasodilators). Nevertheless, they fail to demonstrate any protective value of isoflurane anesthesia, at least when compared with thiopental.

Anesthesia, Inhalation↗

Suppressor T lymphocyte function in patients with idiopathic congestive cardiomyopathy.

Suppressor T lymphocyte function was examined in 11 patients with idiopathic congestive cardiomyopathy and in 11 age and sex matched patients with a similar degree of heart failure resulting from ischaemic heart disease. Suppressor T lymphocyte function was also assessed in a control population of 11 normal subjects. Suppressor T lymphocyte function was reduced in both groups of patients with heart failure but not significantly, and a wide range of suppression was demonstrated in all groups. These data do not support the hypothesis that there is a defect in T lymphocyte function in patients with congestive cardiomyopathy, but they do suggest that there may be a non-specific reduction in T lymphocyte suppressor function associated with heart failure in general.

Adult↗

Immunodeficiency following neonatal thymectomy in man.

Patients undergoing cardiac bypass operations normally have a thymectomy to facilitate cannulation of the great vessels. Laboratory indices of immune function were measured in 18 children aged 9 months to 3 years who had had a thymectomy when aged 3 months or less, and in two groups of controls individually matched for age and age at operation. Total lymphocyte numbers were similar in all three groups but thymectomized children had significantly lower numbers of T cells and T cell sub-sets than controls and showed diminished responses to phytohaemagglutinin and concanavalin A. Children who have had a thymectomy early in life represent an important group in the study of the development of the immune system in man. Although the clinical consequences of early thymectomy are unclear, evidence of impairment of parameters of immunity have been found in later infancy and routine thymectomy in paediatric cardiac surgery should be avoided.

Antigens, Surface↗

Combined familial C7 and C4B deficiency in an adult with meningococcal disease.

A case of meningococcal septicaemia is reported in an adult with a deficiency of the seventh component of complement combined with a deficiency of the B locus product of C4. A family study demonstrated that the two deficiencies were not linked. This is the first time that the individual alleles of C4 were determined in a patient with a deficiency of one component of the terminal pathway. It is possible that the heterogeneous clinical picture of a terminal pathway deficiency may, in part, be explained by the co-existence of other subtle complement defects.

Adult↗

Subclass distribution of IgG autoantibodies in bullous pemphigoid.

The distribution of IgG subclasses in the antibasement membrane zone autoantibody of pemphigoid in skin and serum was analyzed by use of monoclonal antibodies to human IgG subclasses. The predominant subclass was IgG4 which was present in 23 of 24 skin biopsies, IgG1 was next and IgG3 was found only occasionally. In 3 of 24 biopsies IgG4 was the only IgG subclass detected, C3 was absent in 2 of these, the third contained IgM and C3. Serum autoantibodies were similarly analyzed by indirect immunofluorescence (IIF) when again IgG4 autoantibody was the dominant subclass. No IgE autoantibody was detected by IIF.

Aged↗

Microsurgical endarterectomy under barbiturate protection: a prospective study.

Carotid endarterectomy has the potential to improve on the natural history of untreated carotid artery disease with respect to subsequent infarction in symptomatic patients with causative angiographic lesions. This benefit of a reduced risk of stroke can be realized only if the perioperative morbidity and mortality rates are kept low. An approach to symptomatic carotid artery bifurcation disease is outlined, with a defined protocol of microsurgical endarterectomy utilizing barbiturate protection during the period of potential focal temporary cerebral ischemia. This protocol includes preoperative antiplatelet therapy, barbiturate anesthesia, the avoidance of an internal shunt, the use of the operating microscope, and strict control of postoperative hypertension. A series of 200 consecutive endarterectomies performed within this protocol in 180 patients and the resultant combined permanent morbidity and mortality rate of 1.5% are reported.

Adult↗

X-linked mesangiocapillary glomerulonephritis.

Two related male patients with mesangiocapillary glomerulonephritis (MCGN) are described demonstrated by renal biopsy, inherited as an X-linked disorder. Family investigations failed to reveal any underlying immunological defects or a marker for the female carrier state. The age at diagnosis, the result of discovery of proteinuria on routine urine testing during infancy, is earlier than in any other reported cases of MCGN. This raises the possibility that this variety of MCGN may develop in utero and be detectable by alpha-fetoprotein maternal screening.

Genes, Recessive↗

Heme transfer between phospholipid membranes and uptake by apohemoglobin.

The incorporation of CO-heme into single bilayer, egg lecithin vesicles was examined by following the spectral changes that occur when the porphyrin becomes embedded in the membranes. The rate of CO-heme uptake by liposomes is extremely fast (t1/2 less than or equal to 20 ms at 10 degrees C), and the maximum extent is roughly 1 heme/5 phospholipid molecules. This limiting stoichiometry is due to unfavorable electrostatic interactions between the propionate groups of the bound CO-heme. This effect was treated theoretically by attenuating the intrinsic heme partitioning equilibrium constant with an exponential term reflecting the surface potential of the membranes. The surface potential was assumed to be proportional to the concentration of CO-heme in the membranes, and the final expression is Kp = Kop exp[-AHb/VpCp], where Kp is the observed partition constant; Kop, the intrinsic constant; Hb, the concentration of bound heme in the suspension; Vp, the partial molar volume of egg lecithin; Cp, the concentration of lipid phosphate; and A, an empirical constant representing the capacitance of the membrane for heme. For the analysis of kinetic data, the electrostatic term is assumed to apply only to the membrane dissociation rate constant, k-1, and not the association rate constant, k1. The dissociation rate was measured independently either by following the transfer of CO-heme from one vesicle fraction to another or by monitoring heme efflux from the membranes and incorporation into apohemoglobin at high protein concentrations. The data for all three sets of experiments, heme uptake, transfer, and incorporation into globin at 10 degrees C, were fitted quantitatively to the partitioning mechanism using A = 15 M-1, Kop = 5 X 10(5), k1 = 2 X 10(6) s-1, and k0(-1) = 4 s-1. Thus, heme can spontaneously migrate across lipid-water interfaces and hence diffuse rapidly from the mitochondrial inner membrane where it is synthesized to the rough endoplasmic reticulum where it is incorporated into hemoglobin.

Apoproteins↗

Prospective study of cancer in patients with hypogammaglobulinaemia.

Among 377 patients with primary hypogammaglobulinaemia, mainly common variable immunodeficiency (CVID), 316 patients survived the first 2 years after diagnosis and were the subject of a study of cancer incidence. Among the 220 patients with CVID, there was a 5-fold increase of cancer due mainly to large excesses of stomach cancer (47-fold) and lymphomas (30-fold). The excess of stomach cancer is probably related to the high frequency of achlorhydria in CVID. 3 of the 7 patients with stomach cancer and CVID survived for 5 years or longer.

Adolescent↗