Biomedical subjects
Publications and source records attributed to D W Thomas.
Respiratory depression and oversedation occurred during the administration of patient-controlled analgesia because of a broken syringe barrel. Possible complications in the use of patient-controlled analgesia are reviewed. These may be because of prescription or provision errors, patient factors or equipment problems.
An apparently fit young man with sarcoidosis developed complete heart block during an emergency mastoidectomy. A temporary transvenous pacemaker was inserted, but permanent pacing was required in the postoperative period. The clinical and pathological features of cardiac sarcoidosis are described; complete heart block is the commonest presentation of cardiac involvement. The role of anaesthesia as the precipitating factor in this case is discussed.
The results of a screening programme for colorectal neoplasia in a high risk group using an immunochemical test for blood has been reported recently. This test is known as the faecal human haemoglobin (FHH) test. This paper reports the results of rescreening this group after an interval of 1-2 years. The FHH test was compared with a paper disc method. All individuals with positive tests were investigated and those with negative tests were offered investigation. The results confirm the value of the FHH test in screening a high risk group: 19 individuals in 1,153 participants were found to have a significant neoplasm (1.6%). The predictive value of the test for a significant neoplasm was 42%. A false negative rate of 2.6% was found, all lesions being benign. It appears to be more reliable than the paper disc method but the differences do not reach statistical significance. The FHH test is recommended for screening the general population over the age of 40 years, with rescreening annually.
Fitness, weight, blood-pressure, and lipids were measured in 290 women joining a fitness programme. Five years later, 110 (38%) had remained active, and the others had become sedentary again. The net effect of being active was to increase fitness by 18% and to reduce weight by 1.9 kg, diastolic blood pressure by 3 mmHg, and triglycerides by 0.15 mmol/L-1. After controlling for age, weight and fitness, physical activity accounted for 1% and 3% of the variance of changes in systolic and diastolic blood pressure respectively, and was not associated with changes in lipids. Change in fitness accounted for only 1% of change in diastolic blood pressure. More 'active' women gave up smoking than 'inactive' (70% versus 10%). Hypertensive women were more sensitive to changes in weight and fitness than normotensive women. It was concluded that physical activity and change in fitness were only weakly related to changes in blood pressure and were unrelated to changes in lipids.
This study compared the in vitro cytotoxic activity against cultured NIH 3T3 mouse fibroblasts of peripheral blood leukocytes (PBL) from 13 patients with minor recurrent aphthous ulceration (RAU), 5 patients with non-aphthous oral ulceration and 23 age- and sex-matched healthy control subjects. Leukocytes from patients with RAU exerted a significantly greater degree of cytotoxicity towards the 3T3 cells than did those of control subjects. This enhanced cytotoxicity was abrogated by depletion of PBL bearing the CD5 antigen (T-lymphocytes). In contrast, PBL from patients with non-aphthous oral ulceration failed to exert an enhanced cytotoxic activity against 3T3 fibroblasts, when compared to PBL from healthy control subjects. It was concluded that PBL from patients with RAU exert a significantly enhanced cytotoxicity towards an unrelated xenogeneic target cell. This activity is a specific feature of RAU and in the assay system described appears to be mediated by T-lymphocytes.
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We compared Helena "QUIPlates" and Calbiochem "LC-Partigen" radial immunodiffusion systems for their ability to measure fecal concentrations of alpha 1-antitrypsin (FA1AT). Reference ranges for FA1AT concentrations in infants receiving various diets, in children, and in adults are given for each system. FA1AT values obtained with Calbiochem LC-Partigen plates averaged 30% greater than those obtained with Helena QUIPlates, but both systems distinguished between normal and high values. Studies involving variations of usual sample-handling procedures showed that storage at room temperature, repeated freezing and thawing, and long-term storage of frozen samples had no significant effect on measured FA1AT concentration. However, values obtained for lyophilized and nonlyophilized samples did not correlate well.
The mechanism of presentation of foreign antigens to helper T lymphocytes and the nature of the structures involved in this process are not totally understood. It is well documented that this event is carried out by antigen-presenting cells (APC) (e.g., macrophages, dendritic cells, and B lymphocytes) that internalize the antigen, process it, reexpress it on their membrane surface, and present it to the T cell in the context of major histocompatibility complex class II (Ia) molecules. Recent evidence supports the hypothesis that peptide antigens associate directly with Ia molecules on the APC surface membrane. However, the characteristics of other APC membrane structures potentially involved in antigen presentation are not entirely clear. Previous studies in our laboratories identified a guinea pig macrophage membrane-bound, non-Ia-containing antigenic complex (peak A) formed upon incubation of APC with the octapeptide antigen angiotensin (AII). This complex was capable of stimulating AII-immune guinea pig T cells and thus appeared to contain the immunologically relevant form of the antigen. For this reason it was important to establish whether such complex formation with peptides occurs with other cell types and with other peptide antigens. In the present study we found that other types of cells are also capable of forming such a membrane complex with antigen (peak A) and that this event is not unique to AII. Two other peptides, alpha-melanocyte-stimulating hormone and human fibrinopeptide B, both of which are antigenic in mice, were found to form peak A with a number of murine cell lines. As in our earlier studies with guinea pig macrophages, there was no evidence from these experiments for a role for major histocompatibility complex Ia antigens in the peptide binding observed. Differences in both the amount of peak A formation and the pattern of peptide antigen degradation were found from cell line to cell line for a given peptide, and from peptide to peptide for a given cell line, suggesting cellular heterogeneity in peptide processing and retention. In addition, cross-inhibition studies indicated that there was peptide specificity in the formation of peak A perhaps suggestive of molecular heterogeneity in the structure of peak A. These results indicate that there may be several types of cell surface molecules that specifically bind and retain peptide antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
The prevalence of colic with respect to the type of milk feeding in the first 17 weeks of life was assessed by questioning the parents of 964 healthy infants aged 2 to 52 weeks. There was a similar prevalence of colic in infants fed human milk (20%), formula (19%), and formula-supplemented human milk (21%). Intestinal damage, determined by measuring random fecal alpha 1-antitrypsin concentrations in 206 infants aged 2 to 17 weeks and fecal hemoglobin concentrations in 200 of these, was not more likely in infants with colic at the time of study. The occurrence of adverse reactions at the time of introduction of fresh whole cow's milk into the diet of previously colicky infants was uncommon. Our results suggest that dietary protein hypersensitivity is probably not the cause of colic in most healthy young infants.
Malignant hyperpyrexia developed, and was successfully treated, in a 50-year old man undergoing pyelolithotomy. Early diagnosis with the assistance of end-tidal carbon dioxide monitoring facilitated prompt treatment with i.v. dantrolene. A positive muscle biopsy subsequently confirmed the diagnosis. The only likely triggering agent used was isoflurane.
A group of 1615 asymptomatic individuals presumed to be at increased risk of colorectal neoplasia were selected as the study group. All were tested by an immunochemical test for faecal occult blood. In the second half of the study, individuals who were occult blood negative were offered colonoscopy. Ninety-nine individuals (6.1%) returned stools which were occult blood positive. Investigation by full colonoscopy was possible in 90 cases, revealing nine patients (10%) with invasive cancers, four patients (4.4%) with carcinomata in situ, and 36 patients (40%) with adenomata. Non-neoplastic pathology capable of producing occult blood positive stools was found in 31 individuals (34.4%). No pathology was found in 10 instances (11.1%). Of the 53 occult blood negative subjects who underwent colonoscopy, eight were found to have adenomata. Only one of these was larger than 5 mm in diameter (18 mm). No carcinomata were found. The site within the large bowel of the tumour did not appear to significantly affect the occult blood status of the faeces but the size of the tumours detected suggests that the presence of blood within the stool is more likely to be associated with larger lesions. The frequency of detection of both carcinomata and adenomata was greatest in individuals who had a past history of colorectal neoplasia. The individual cost of this immunochemical test is nominal. The high diagnostic yield and low false positive and negative rates suggest that case follow-up, surveillance, or screening utilizing this test is justified.
Alpha-1-antitrypsin concentration was analyzed by immunoelectrophoresis in samples of human colostrum (n = 3) and of mature milk from mothers between 2 to 52 wk postpartum (n = 39), one of whom was known to be PiMZ with a PiZZ infant. All milk samples tested contained alpha-1-antitrypsin. The three colostrum samples contained 140, 520, and 250 mg/liter. The mature milk of women who had been lactating less than 6 months had a higher concentration (7.2 +/- 3.6 mg/liter) (mean +/- SD) than in the women who had been lactating 6-12 months (4.8 +/- 1.8 mg/liter) (p less than 0.03). The milk of the woman of Pi type MZ had an alpha-1-antitrypsin concentration of 7.0 mg/liter at 7 wk postpartum and 4.1 mg/liter at 52 wk. It has been previously demonstrated that enhanced absorption of intact proteins occurs in early infancy. The presence of antiproteases in human milk provided during early infancy may serve to inhibit the absorption of intact proteases, limiting their entry into the portal circulation.
To study the role of antigen-presenting cells (APC) in T lymphocyte responses, the stimulation requirements of a murine T cell hybridoma specific for the peptide antigen human fibrinopeptide B (hFPB)/I-Ak was examined. The fine specificity of T cell recognition of this peptide was determined by using several hFPB homologs and analogs, which indicated that the intact 14-amino acid peptide must remain intact to preserve the antigenic determinant, and that the carboxyl terminal Arg14 was important for T cell responses. Of particular interest was the finding that APC-associated hFPB failed to stimulate the T cells, and that activation was only observed with soluble peptide or by brief hFPB treatment of the T cells and APC mixed together. In addition, hFPB covalently bound to agarose beads was able to cause T cell activation, provided that I-Ak+ APC were also present in the culture. A number of control experiments were performed that showed that hFPB was not released from the bead and that the antigenic peptide involved in T cell responses remained bound to the beads. These results indicate that the form of the hFPB peptide antigen recognized by this T cell can be provided separately from APC.
In this study we examined the mechanism by which a PPD-specific murine T cell hybridoma, 8B2, recognized PPD associated with antigen-presenting cells (APC) in a manner genetically restricted by I-Ad. It was found that PPD-pulsed APC that were glutaraldehyde-fixed and treated with anti-Ia monoclonal antibody (abbreviated as PGM) were unable to stimulate the 8B2 T cells, as expected, due to inhibition caused by antibody binding to the Ia. However, addition of non-antigen-treated, glutaraldehyde-fixed APC (abbreviated as G) to cultures containing 8B2 T cells and PGM restored T cell activation, as determined by IL 2 production. This second non-antigen-specific function provided by the additional APC, G, was attributed to Ia and could be substituted by APC plasma membranes and by soluble membrane extracts. Genetic restriction analysis in which a variety of Ia-positive and Ia-negative cell lines and B cell blasts from different mouse strains were used as PGM or as G showed that each APC provided different Ia determinants that were specifically recognized by the T cells. PGM cells had to express I-Ad in order to present the PPD determinant, whereas the non-antigen-specific function was specific for I-Ad or I-Ab. These results suggest that the anti-Ia antibody does not interfere with the PPD/I-Ad-specific determinant bound by the antigen-specific T cell receptor, but prevents a second non-antigen-specific interaction with another region of the Ia molecule, which is provided by G. These two roles for Ia (antigen-specific and non-antigen-specific) were also found for activation of normal polyclonal PPD-specific T cell responses; thus they are not unique to the 8B2 T cell, but are generally applicable. In addition, T cell interactions with PGM and with G each provide different intracellular activation signals. This was determined by substituting the PGM or the G with either the tumor promoter phorbol 12-myristate 13-acetate (PMA) or the Ca++ ionophore, ionomycin. It was found that 8B2 T cells cultured with PGM and ionomycin, but not with PGM and PMA, were activated for IL 2 production. Neither PMA nor ionomycin in conjunction with G resulted in T cell activation. Taken together, these results indicate that 8B2 T cell activation involves APC Ia antigens in two different ways: one is to contribute to the presentation of the foreign PPD antigen, and a second is a non-antigen-specific Ia-T cell interaction necessary to provide additional intracellular activation signals.(ABSTRACT TRUNCATED AT 400 WORDS)
Malondialdehyde measurements have been the major tool for studying relationships between lipid peroxidation and tissue pathology. Recently, we presented a novel gas chromatography-mass spectrometry method for direct detection of phospholipid peroxides with picogram sensitivity based on transesterification of phospholipids or triglycerides to form pentafluorobenzyl esters. Under some circumstances the reactive primary oxidation products break down. Therefore, we developed a convenient, high sensitivity method to detect more stable secondary lipid oxidation products, the 4-hydroxyalkenals. The method accomplishes a facile extraction of 4-hydroxynonenal from tissues by forming pentafluorobenzyl oxime derivatives to displace aldehydes from Schiff base linkages. 4-hydroxynonenal was found in heart, liver, adrenal, and testis from rats and was detected to the 10-100 pg level by the current method.
To examine T lymphocyte recognition of foreign antigen, specific responses to the photoreactive antigen N-hydroxysuccinimidyl 4-azidobenzoate (HSAB) were determined by using an HSAB/I-Ad-reactive murine T cell hybridoma. It was found that covalent coupling of HSAB to aminoethyl polyacrylamide beads at particular densities directly activated the T cells for IL 2 production, and beads conjugated at higher or lower doses of HSAB were nonstimulatory. This stimulation was specific for the phenyl ring composition of HSAB and for HSAB-reactive T cells. In addition, T cell activation by HSAB-coupled beads was specifically inhibited by soluble monomeric HSAB-glycine. These results indicate that HSAB-specific T cells may be directly stimulated by insolubilized HSAB in the absence of Ia antigens, suggesting direct T cell binding of foreign antigen.
We have observed the development of chronic inflammatory bowel disease, indistinguishable from Crohn disease, in two boys with glycogen storage disease type Ib (GSD-Ib). A chance association of these diseases in two patients is unlikely. Studies of their neutrophils showed severe chronic neutropenia (mean absolute granulocyte counts of less than 500 cells/microliter) and markedly deficient chemotactic response (less than 5% of reference values) in the patients with GSD-Ib and normal neutrophil values in four patients with glycogen storage disease type Ia (GSD-Ia). Monocyte counts and responses to chemotactic stimulation were normal in both GSD-Ia and GSD-Ib. Chronic inflammatory bowel disease appears to be associated with GSD-Ib, and neutrophil abnormalities may be involved in the pathogenesis of the bowel inflammation.