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Biomedical subjects

J Wiggins

Publications and source records attributed to J Wiggins.

At least 73 records · Page 4Linked to original sources

Coagulopathy and platelet activation in Kawasaki syndrome: identification of patients at high risk for development of coronary artery aneurysms.

Prospective evaluation of platelet activation and hypercoagulability was performed in 31 patients with Kawasaki syndrome. Most patients had elevated acute-phase reactants when studied during the first 3 weeks of their illness; 17 of 25 (68%) patients had factor VIII activity greater than 150%, 18 of 24 (75%) had fibrinogen greater than 400 mg/dl, and 17 of 31 (55%) had a platelet count greater than 450,000/mm3. Antithrombin III was depressed initially in 17 of 25 (68%) patients. Depleted fibrinolytic activity, as measured by a euglobulin lysis time greater than 300 minutes, was documented in nine of 20 (45%) patients. Plasma beta-thromboglobulin (BTG) measured at 0 to 3 weeks was elevated (greater than 43 ng/ml) in seven of 24 (29%) patients. All patients with coronary artery aneurysms had elevated BTG values. The mean BTG in the group with aneurysms was 72.3 ng/ml when measured during the first 3 weeks after onset of fever, and 87.7 ng/ml at 4 to 7 weeks. The group without aneurysms had mean BTG values of 29.4 and 28.3 ng/ml at 0 to 3 and 4 to 7 weeks, respectively. The difference between the two groups was significant (P less than 0.002) for both the initial and later values. An elevated BTG during the first 3 weeks after onset of fever was highly associated with aneurysm formation in our patients (P less than 0.007). No aneurysms occurred in patients with a normal BTG value.

Aneurysm↗

Influence of fine structure of lipid A on Limulus amebocyte lysate clotting and toxic activities.

We examined the relationship between the fine structure of lipid A and the toxicity of endotoxin or lipopolysaccharides as measured by the Limulus amebocyte lysate (LAL), rabbit pyrogenicity, chicken embryo lethal dose, and dermal Shwartzman reaction tests. Lipid A and lipid A-like compounds obtained from deep-rough mutants of Salmonella spp. and Escherichia coli had a wide range of structural variations. These compounds included native lipopolysaccharides, diphosphoryl and monophosphoryl lipid A's, and lipid X (a monosaccharide). The LAL test was positive for all lipids tested with lysates from Travenol Laboratories and from Associates of Cape Cod (2.9 X 10(3) to 2.6 X 10(7) endotoxin units per mg), except for O-deacylated and dephosphorylated lipid X, which were negative. The Mallinckrodt lysate gave negative tests for lipid X. In the rabbit pyrogenicity and chicken embryo lethal dose tests, only native lipopolysaccharide and diphosphoryl lipid A's were judged toxic. The Shwartzman reaction was positive for a specific purified diphosphoryl lipid A (thin-layer chromatography-3 fraction) but negative for the purified monophosphoryl lipid A (also a thin-layer chromatography-3 fraction). These results show that the LAL test is not a valid measure of all parameters of toxicity of a lipid A or lipid A-like compound and can yield false-positive results. However, these findings are not in conflict with the widespread use of the LAL assay for pyrogens in the pharmaceutical industry since a good correlation exists between LAL results and pyrogenicity when undegraded endotoxin is evaluated in parallel assays.

Animals↗

The secretory IgA system of lung secretions in chronic obstructive bronchitis: comparison of sputum with secretions obtained during fibreoptic bronchoscopy.

The constituents of the secretory immunoglobulin A system (dimeric IgA, total secretory component and free secretory component) were measured in sputum sol phase, tracheal aspirates, and bronchoalveolar lavage fluids from 15 patients undergoing fibreoptic bronchoscopy. All of the proteins showed a progressive decrease in concentration from sputum to the bronchoalveolar lavage fluids (2p less than 0.001). Standardisation of samples by means of protein concentration ratios showed that all secretions were generally similar in respect of their secretory IgA profiles, although major differences remained in some individual patients. The between patient variability of the results was generally reduced by the use of protein concentration ratios, allowing closer comparison between subjects. When the secretion albumin concentration was used as a standard, however, it increased the variability of the sputum sol phase IgA components (2p less than 0.01), whereas it decreased the variability of the IgA components in the bronchoalveolar lavage fluid (2p less than 0.05). The role of albumin as a standard protein for assessing the secretory IgA system in lung secretions remains uncertain.

Aged↗

Variability in the secretory IgA system in sputum sol phase in stable chronic obstructive bronchitis.

Within and between patient variability in the sputum sol phase secretory IgA system was studied in 31 patients with clinically stable chronic obstructive bronchitis. Within patient coefficients of variation (CV) were similar for secretory component (SC), free secretory component (FSC), total immunoglobulin A (IgA) and the immunological amount of IgA present in its dimeric (11S) form (average CV 32%). The immunological proportion of IgA present in the dimeric form was about 70% of the total and relatively constant (average CV 7%). Between patients, variability was greater but also similar for SC, FSC, total IgA and the amount of dimeric IgA (average CV 50%). The proportion of IgA present in dimeric form was again less variable (CV 21.1%). 'Standardisation' of samples, using protein ratios to either albumin or the 'local' components of the secretory IgA system, did not produce variability. Furthermore, the effect of such standardisation was to increase the between patient variability for total IgA and FSC (2p less than 0.01). However, despite this variability, 4 patients studied previously remained clearly distinct, suggesting defects of the secretory IgA system. The methods described provide a means of identifying such patients.

Aged↗

Surgical therapy for a complication of Kawasaki's disease.

Mucocutaneous lymph node syndrome (MLNS), or Kawasaki's disease, affects thousands of infants and children each year and is associated with a high incidence of coronary artery aneurysm, which may lead to subsequent myocardial infarction. Successful use of the right subclavian-axillary artery to bypass a thrombosed aneurysm of the left anterior descending coronary artery is documented angiographically and forms the basis of this report. A management plan for MLNS patients is proposed.

Aneurysm↗

Autoantibodies to SS-A/Ro in infants with congenital heart block.

Antibodies to SS-A/Ro have been proposed to be a serologic marker for the neonatal lupus syndrome, which is characterized by congenital heart block or cutaneous lupus or both. The antibodies occur in the mother and are transiently found in the child's serum. We examined an unselected series of 12 children with idiopathic CHB, isolated in 10 children and with cutaneous lupus lesions in two. Six of these children and their mothers were studied during the child's neonatal period, and six were studied retrospectively. All six neonates had SS-A/Ro autoantibodies. Nine of 12 mothers had SS-A/Ro autoantibodies. Of the seropositive mothers, one had systemic lupus erythematosus, two had sicca syndrome, one had photosensitivity, one had arthralgias, and four were asymptomatic. We propose that congenital heart block may be related to transplacental passage of maternal SS-A/Ro antibodies and that neonatal lupus may be the most common cause.

Adult↗

Lung secretion sol-phase proteins: comparison of sputum with secretions obtained by direct sampling.

The protein content of tracheal secretions and of bronchial lavage and bronchoalveolar lavage fluid was compared with that of sputum in 33 patients who underwent fibreoptic bronchoscopy. The secretion-to-serum concentration ratios for albumin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and immunoglobulin A (IgA) fell progressively as samples were obtained from further down the bronchial tree, probably reflecting greater sample dilution. The secretion-to-serum protein ratios when standardised for the corresponding albumin ratio were similar in all secretions studied. In particular, the IgA ratios were about eight times those of albumin and alpha 1-antichymotrypsin ratios were about twice those of albumin, suggesting similar degrees of "local production" of these proteins in all secretions studied. Some patients showed considerable differences in IgA ratios between sputum and bronchial lavage fluid. The significance of these differences is not clear.

Adult↗

Variability in sputum sol phase proteins in chronic obstructive bronchitis. The value of using albumin for standardization.

The variability of sputum sol phase proteins was studied in 27 patients with stable chronic obstructive bronchitis. Within individual patients (n 1/2 11), variability over 5 consecutive days was similar for each of 4 proteins studied: average coefficient of variation (CV) for albumin was 39.8% for alpha 1-antitrypsin (alpha 1AT), 32.1%, for alpha 1-antichymotrypsin (alpha 1ACh), 26.6%, and for immunoglobulin A (IgA), 35.1%. The calculation of sputum-to-serum ratios did not affect this variability. Between patients (all patients studied on a single day) the variability of sputum sol phase proteins was greater (CV: albumin 1/2 84.5%, alpha 1AT 1/2 90.1%, alpha 1ACh 1/2 58.3%, and IgA 1/2 71.6%) and was also unaffected by the use of sputum-to-serum concentration ratios. "Standardization" for albumin reduced the average within-patient variability for sputum alpha 1AT (CV from 32.1 to 19.7%) but it had no effect on alpha 1ACh and IgA. However, although between-patient CV for sputum alpha 1AT was also reduced (from 90.1 to 53.4%, 2 p less than 0.01) it significantly increased for alpha 1ACh (from 58.3 to 86.0%, 2 p less than 0.05) and IgA (71.6 to 170.1%, 2 p less than 0.001), suggesting that such standardization may be inappropriate for these proteins.

Aged↗

Effect of corticosteroids on sputum sol-phase protease inhibitors in chronic obstructive pulmonary disease.

Corticosteroids caused a reduction in the ratio of sol-phase sputum concentration to serum concentration of albumin in 12 patients with chronic obstructive bronchitis, suggesting a reduction in protein transudation. Alpha-1-antitrypsin values followed the same pattern as those of albumin in both the control and treatment periods, confirming the similar behaviour of the two proteins. The alpha 1-antichymotrypsin ratios were on average three times higher than those of albumin in the control period, confirming the presence of local mechanisms in the lung for preferentially concentrating this protein. The sputum-to-serum ratio of alpha 1-antichymotrypsin, however, rose during steroid treatment with the result that there was a selective increase in this protease inhibitor, which may be of potential benefit to such patients.

Bronchitis↗

The effect of X-537A (lasalocid) on potassium contracture in rat ventricular muscle.

The effects of the carboxylic ionophore X-537A on contracture induced by high external K+ were determined in stimulated and unstimulated rat papillary muscles. X-537A (5 X 10(-6) M - 10(-5) M) increased peak K+-contracture force in stimulated but not unstimulated muscle. X-537A may alter myocardial force development by influencing transport of Ca2+ across the sarcolemma or Ca2+ release from sarcoplasmic reticulum.

Animals↗

Hepatic injury following feprazone therapy.

Two cases of feprazone-induced hepatic injury are reported. Both patients developed jaundice within one month of commencing therapy. Histological investigation showed a granulomatous reaction in one case and hepatitic changes in the other. The changes were similar to those seen as a complication of phenylbutazone therapy. When the administration of feprazone was discontinued both the clinical and biochemical changes were resolved.

Adult↗

Eucalyptus oil poisoning.

Accidental ingestion of eucalyptus oil by a 3-year-old boy caused profound central nervous system depression within 30 minutes, but he recovered rapidly after gastric lavage. The extreme toxicity of eucalyptus oil is emphasised.

Child, Preschool↗

Pulmonary vascular extraction of circulating norepinephrine in infants with bronchopulmonary dysplasia.

Although the pulmonary circulation in infants with advanced bronchopulmonary dysplasia (BPD) is characterized by abnormal structure and vasoreactivity, metabolic lung functions have not been studied in these infants. To test the hypothesis that patients with severe BPD may have abnormal metabolic lung function, we assessed the pulmonary vascular extraction of circulating norepinephrine in six children with BPD during cardiac catheterization. Plasma norepinephrine levels were measured from simultaneously drawn mixed venous (main pulmonary artery) and left atrium or femoral artery samples. In comparison with four infants with mild heart disease without pulmonary hypertension, we found that infants with BPD extract proportionately less norepinephrine than non-BPD infants [-7 +/- 50% (BPD) versus +27 +/- 6% (non-BPD); P less than 0.001, t test]. Three infants with BPD had higher arterial than mixed venous concentrations of plasma norepinephrine, suggesting net production across the lung. Plasma catecholamine levels and percent extraction correlated poorly with cardiac index and systemic and pulmonary vascular resistance indices. However, this study group was characterized by a high incidence of pulmonary (6/6) and systemic (4/6) hypertension, left ventricular hypertrophy (4/6), and subsequent death (3/6). We conclude that infants with severe BPD and pulmonary hypertension have decreased pulmonary vascular clearance or net production of circulating norepinephrine, but links between altered pulmonary catecholamine metabolism and pulmonary hypertension, or other cardiovascular abnormalities associated with BPD, remain speculative.

Bronchopulmonary Dysplasia↗

Variant angina in an adolescent.

We describe a case of variant angina associated with acute myocardial ischemia in an adolescent presenting with severe chest pain and transient ST elevation. Subsequent cardiac catheterization revealed normal coronary anatomy, and the patient has been asymptomatic since discharge on calcium channel blockers. Variant angina is a rare cause of chest pain in adolescents.

Adolescent↗