Detection of clinically significant coronary artery disease in hypertensive patients. Echocardiographic study.
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Biomedical subjects
Publications and source records attributed to J R Dawson.
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The haemodynamic effects of oral and intravenous salbutamol were investigated in 22 patients with chronic heart failure. Intravenous salbutamol (13 micrograms/min) increased cardiac index by 53 per cent from 1.5 +/- 0.13 1/min per m2 to 2.3 +/- 0.23 1/min per m2 and decreased systemic vascular resistance by 28 per cent from 29.4 +/- 3.9 units to 21.2 +/- 2.5 units. Heart rate rose by 10 per cent from 101 +/- 3.5 beats per minute to 111 +/- 3.2 beats per minute and pulmonary artery end-diastolic pressure fell by 13 per cent from 26.3 +/- 1.8 mmHg to 22.8 +/- 2.1 mmHg. Similar results were obtained after oral salbutamol (8 mg). Cardiac index rose by 40 per cent and systemic vascular resistance fell by 30 per cent. There was a small rise in heart rate and a variable and not significant change in pulmonary artery end-diastolic pressure. Experiments on isolated rabbit papillary muscle showed that salbutamol, at the concentration which exists in patients, had no detectable positive inotropic effect. It is probable that the increase in cardiac output in patients is primarily the result of reduced afterload caused by vasodilatation. Salbutamol is a useful drug in the treatment of chronic heart failure.
Intravenous salbutamol (13 microgram/min) has been given to 31 patients with cardiogenic shock complicating acute myocardial infarction. Haemodynamic measurements were made in nine of these patients. Salbutamol increased cardiac index by 41 per cent from 1.25 +/- 0.06 l/min per m2 to 1.76 +/- 0.19 l/min per m2 and decreased systemic vascular resistance by 16 per cent from 26.2 +/- 1.9 units to 21.9 +/- 2.1 units. Heart rate rose by 13 per cent from 95 +/- 4.5 beats/min to 106 +/- 6.0 beats/min. Pulmonary artery end-diastolic pressure fell from 20.6 +/- 1.7 mmHg to 16.9+/- 1.9 mmHg. Of the 31 patients, eight survived to leave hospital (27%). Five of the survivors had initial low heart rates and in these patients the clinical improvement was probably attributable to the positive chronotropic action of salbutamol. In the remaining three survivors clinical improvement was probably a result of salbutamol mediated afterload reduction. Salbutamol may be useful in the treatment of cardiogenic shock and pump failure complicating acute myocardial infarction.
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Ascitic fluids from ovarian cancer patients which contained a component (lymphocyte-inhibitory activity) that inhibited the blastogenic responses of normal lymphocytes were tested for their effect on established lymphoblastoid cell lines. These ascites fluids inhibited proliferation as measured by [3H]thymidine uptake and cell growth in vitro of two different B- (SB and IM-1) and two different T- (HSB and CEM) lymphoblastoid cell lines but were not cytotoxic. No difference in the sensitivity of T- and B-lymphoblastoid cell lines to the active component in the ascites fluids could be demonstrated. In contrast, established nonlymphoid cell lines (HEp-2, oligodendroglioma, and bladder tumor cell lines) were unaffected by the ascites fluids. Two different preparations of partially purified lymphocyte inhibitory activity from these ascites fluids also inhibited lymphoblastoid cell line proliferation. In addition, both B- and T-lymphoblastoid cell lines absorbed and/or metabolized the lymphocyte-inhibitory activity at 37 degrees but not at 4 degrees. These data suggest that the inhibition of lymphoblastoid cell line proliferation and the inhibition of the blastogenic responses of normal lymphocytes by the ascites fluids are attributable to the same or similar factors.
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A radioimmunoassay was developed for secretory component, a glandular epithelial cell product secreted as an accessory protein with dimeric immunoglobulins A and M. Forty-four normal women between the ages of 40 and 70 had plasma concentrations of secretory component of 7.195 microgram/ml +/- 3.590 (+/-2 SD). Of the patients with metastic breast cancer of epithelial origin, 34 (91.9%) had plasma concentrations greater than 8.990 microgram/ml; 29 (78.1%) had plasma concentrations greater than 10.785 microgram/ml; 10 (27%) had concentrations greater than 15.000 microgram/ml; and 3 (8.1%) had concentrations greater than 22.710 microgram/ml. Serial plasma concentrations (averaging 3.48 per patient) of 35 (94.6%) of these patients reflected the clinical course of the disease. All patients had some combination of surgery, radiation therapy, and chemotherapy. No direct correlation was noted between the type of therapy and concentration of secretory component. However, plasma secretory component served as a marker in the systemic circulation of a change in the status of the metastatic breast cancer. The impact of this research may lie in its incorporation into clinical management.
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Cyst fluids from mucinous cystadenocarcinoma of the ovary show significant concentrations of carcinoembryonic antigen (CEA) activity. This CEA activity was compared to several colon CEA standards with respect to size, concanavalin A binding, and immunological activity. CEA activity in unfractionated ovarian cyst fluid was indistinguishable from CEA standards by gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The cyst fluid CEA activity showed identity with various CEA standards by double immunodiffusion in agar gels and by radioimmune competition assay. Attempts to purify the cyst fluid CEA by perchloric acid extraction prior to gel filtration chromatography were unsuccessful. The yield of soluble CEA activity following perchloric acid extraction averaged 10%, and in one cyst fluid, qualitative changes were noted in the soluble antigenic activity. Ovarian cyst fluid CEA activity was bound by concanavalin A-Sepharose 4B and specifically eluted with competing monosaccharide. Lectin affinity chromatography and gel filtration chromatography over Sepharose 4B and Sephadex G-200 can be used to purify cyst fluid CEA from whole fluid or lyophilized and reconstituted samples.
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A radioimmunoassay was designed for the detection of secretory protein, a component of secretory immunoglobulin A, in human serum. The assay uses free secretory protein isolated from human colostrum, and antisera raised in rabbits to the purified antigen. The mean level of secretory protein in the control group was 2.34 +/- 0.41 microgram/ml (mean +/- S.E.M.). The level in cord blood was slightly lower (0.74 +/- 0.26 microgram/ml), while the level in patients with ovarian carcinoma was significantly increased (12.67 +/- 1.43 microgram/ml). Pregnant women have increasing secretory protein levels with increasing length of gestation (5.86 +/- 2.02, 11.55 +/- 1.30 and 17.00 +/- 1.16 microgram/ml for the first, second and third trimesters, respectively.
A secretory component (SC) was detected by radioimmunoassay in the cyst fluids, ascitic fluids, and sera from patients with ovarian adenocarcinomas. Serous cyst fluids and ascitic fluids showed lower levels (expressed as means +/- SE) of SC (1.37 +/- 0.37 and 1.24 +/- 0.24 microgram/ml, respectively) than mucinous cyst fluids (181.50 +/- 50.40 microgram/ml). SC levels in the sera of all patients with ovarian adenocarcinoma were high (12.67 +/- 1.43 microgram/ml) when compared to SC levels in the sera of normal individuals (2.34 +/- 0.41 microgram/ml). Sera from patients with ovarian cancers diagnosed as serous, mucinous, papillary, and poorly differentiated adenocarcinomas showed SC levels of 9.93 +/- 1.68, 22.44 +/- 3.24, 7.35 +/- 1.13, and 10.10 +/- 1.58 microgram/ml, respectively.
Peripheral blood lymphocytes from 15 patients with hypernephroma were stimulated with partially purified tumor plasma membranes to incorporate [3H]thymidine. Kidney tumor and normal kidney membranes were adjusted to antigenic equivalence as determined by their ability to inhibit in the HLA 51Cr microcytotoxicity assay. Membranes from control "normal" kidney adjacent to the tumor stimulated less than did the tumor. Six of eight patients responded to autologous tumor (p less than 0.05). One patient responded to allogeneic tumor of the same histological type. The importance of statistical analyses of tumor membrane lymphocyte stimulation data is discussed in relation to the assay system. Sequential studies suggest that this assay may be useful as a guideline for the monitoring of current therapeutic regimens and future immunotherapy. The results of this assay are discussed in relation to other in vitro tumor lymphocyte stimulation assays. The limitations of this assay appear to be two: (a) it can be used only in large tumor systems where there is adequate tissue for analysis and controls; (b) it may detect nontumorous antigens or nonspecific stimulators in allogeneic studies. Further studies are needed to correlate the blastogenic response with the patient's prognosis.
Cystic effusions from 12 epithelial tumors of the ovary and pooled normal ovarian tissue were studied by immunodiffusion for the presence of immunoglobulins G (IgG), M (IgM), and A (IgA) and free secretory component (FSC). In pooled normal ovarian tissue, IgG was the only immunoglobulin detected. In the neoplastic samples studied, IgG was detected in each of the 12 samples (100%), IgM was found in 10 of the 12 samples (83%), and IgA was detected in 11 of the 12 samples (92%). There was no discernible correlation between the immunoglobulins detected and the composition of the effusions or the pathologic classification of the tumors. FSC was detected in all mucinous samples studied, malignant as well as benign. This substance was not detected in any of the nonmucinous samples or in pooled normal ovarian tissue. The data suggest a correlation between the presence of FSC and the mucinous composition of the tumor effusion. Possible use of FSC assays in the study of mucinous tumors of the ovary is discussed.