The character of transient myocardial ischemia: clinical studies and progress using positron emission tomography.
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Biomedical subjects
Publications and source records attributed to M Shea.
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Patients with angina and coronary artery disease (CAD) have many episodes of transient ST-segment depression during ordinary daily life, and these are often asymptomatic. To investigate this signal as a marker of myocardial ischemia, 30 patients with chronic stable angina and CAD underwent positron tomography, recording the regional myocardial uptake of rubidium-82, pain and ST-segment changes before, during and after 59 technically satisfactory exercise tests, 35 cold pressor tests and 22 episodes of unprovoked ST depression. Exercise resulted in 53 episodes of ST depression with angina and in 5 episodes without pain. After cold pressor tests, there were 3 episodes of ST depression and pain and 12 of painless ST depression. Only 9 episodes of unprovoked ST depression were accompanied by pain. Tomography showed independent evidence of ischemia in 63 (97%) of the total 65 episodes of ST depression with angina and in all 30 episodes of painless ST depression. In each patient perfusion defects occurred in the same myocardial segment during painful and painless ST depression and responses were significantly different from those in 16 normal subjects studied in the same way. These findings support the use of transient ST depression in continuous monitoring to assess the activity of CAD, but only in patients with typical angina pectoris, ST depression during exercise and proved CAD. They strengthen the evidence derived from ambulatory monitoring for a wider picture of the disease than is generally appreciated, with more frequent episodes of silent myocardial ischemia than of angina pectoris.
Patients with angina and coronary disease have many episodes of symptomless transient myocardial ischaemia, most of which cannot be explained by physical exertion. 16 patients with typical stable angina pectoris were examined to test the hypothesis that these episodes can be triggered off by ordinary daily events, such as changes in mental activity. Regional myocardial perfusion and ischaemia were assessed by measurement of the uptake of rubidium-82 with positron tomography after mental arithmetic and physical exercise. With mental arithmetic, 12 (75%) patients had abnormalities of regional perfusion, accompanied in only 6 by ST-segment depression and in 4 of these 6 by angina, leaving 6 patients with perfusion abnormalities but neither pain nor electrocardiographic changes. After exercise, all the patients showed abnormal regional myocardial perfusion in the segments that became ischaemic with mental arithmetic. This was accompanied by ST depression in all and angina in 15. The association between mental activity and myocardial ischaemia may operate frequently during everyday life and may explain many of the transient and symptomless electrocardiographic changes in patients with coronary disease.
A simple technique using reverse-phase ion-pair liquid chromatography for measurement of exogenous thiosulfate is described. Accurate measurement of thiosulfate in plasma and urine was permitted by precolumn derivatization with monobromobimane, a substance that readily yields fluorescent compounds upon reaction with a variety of biologically important nucleophiles including glutathione, cysteine, and sulfite. Using an injection volume of 50 microliters, as little as 0.16 nmol of thiosulfate was reliably measured. The interassay precision of the method was reflected by a coefficient of variation of 7.7% while the coefficient of variation for interassay analysis was 2.6%. Recovery of thiosulfate from plasma was 96.9 +/- 3.2% and greater than 98% from urine. The simplicity, sensitivity, and precision of the method make it ideal for the study of thiosulfate and other important nucleophiles in body fluids.
Sodium thiosulfate kinetics were studied in eight subjects, six of whom were given the drug as a cisplatin neutralizer. Thiosulfate at a dose of 12 gm/m2 was injected by continuous intravenous infusion over 6 hr. Under these conditions, steady-state plasma concentrations were not achieved and apparent volume of distribution could not be calculated. The drug was eliminated from plasma by first-order kinetics, and the data best fit a one-compartment kinetic model with a t1/2 (mean +/- SD) of 80 +/- 38 min. Total body thiosulfate clearance was 190 +/- 76 ml/min/m2 and renal clearance was 50 +/- 11 ml/min/m2. The plasma elimination t1/2 and renal thiosulfate clearance correlated poorly with clearance of endogenous creatinine. Only 28.5% +/- 9.4% of the thiosulfate was recovered unchanged in the urine. Urinary excretion was rapid, with approximately 95% of recoverable drug eliminated within 4 hr after termination of the infusion. No toxic effects of thiosulfate were observed. These data provide the basis for the rational development of dose schedules when sodium thiosulfate is used as a cisplatin neutralizer.
To determine the physiological effect of coronary artery bypass surgery and the mechanisms for pain relief, 15 patients with exertional angina were studied before and after operation. Before the operation conventional tests included exercise tests (all positive) and coronary angiography (all patients had greater than or equal to 70% stenosis of major vessels). In addition, ambulatory electrocardiographic monitoring during 48 hours detected 92 episodes (greater than or equal to 1 mm) of ST depression. Regional myocardial perfusion was assessed with positron tomography using rubidium-82 (t1/2 78 s) and this showed reversible inhomogeneity with absolute regional reduction of cation uptake after exercise in all 15 patients. After coronary surgery 10 of the 15 patients had (a) no angina, (b) patent grafts (three or more), (c) no evidence of ischaemia during ambulatory monitoring out of hospital, and (d) homogeneous perfusion with reversal of the disturbances in regional myocardial perfusion after exercise. After operation one of the 15 patients had no angina and showed silent infarction in the segment that was previously ischaemic but supplied by a patent graft. All but one of the remaining patients had no angina, patent grafts, but disturbances of regional myocardial perfusion with silent ischaemia on exercise. Two of these patients continued to have asymptomatic and ischaemic episodes of ST depression during ambulatory monitoring out of hospital. This physiological study of regional myocardial perfusion in patients in hospital and in those with ischaemia out of hospital showed that three different mechanisms may account for the relief of pain--improved perfusion, infarction, and silent ischaemia. Silent ischaemia in particular raises puzzling pathophysiological and therapeutic questions that may affect prognosis and the interpretation of clinical trials.
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Pars plana vitrectomy was carried out in 140 patients with useful to excellent visual acuity associated with elevated proliferative diabetic retinopathy. A substantial reduction in the incidence of traction retinal detachment occurred and a significant improvement in visual prognosis was achieved.
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Early vitrectomy was carried out in 22 eyes with proliferative diabetic retinopathy and evidence of partial vitreous detachment in 17 patients with insulin-dependent diabetes. All the eyes had undergone panretinal laser photocoagulation, and all had a visual acuity of 6/12 or better, but 13 had had a vitreous hemorrhage. After a mean follow-up period of 29 months 19 of the eyes had retained the same visual acuity, 18 had been free of renewed vitreous hemorrhage for 6 months, there had been no macular retinal detachments and all the anterior segments were normal. The three instances of persistent visual loss were due to recurrent vitreous hemorrhage.
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Of 28 patients with a foreign body in the posterior segment, 24 were managed primarily and 4 had been referred for treatment of associated injuries or complications after extraction. There were 19 magnetic and 9 nonmagnetic (including 6 copper-containing) foreign bodies. Preoperative localization was achieved mainly by visual and radiologic (Sweet's) methods, supplemented by computer-assisted tomography and ultrasonography. The magnetic foreign bodies were extracted through the pars plana or sclera. The nonmagnetic foreign bodies were extracted mainly by a two-instrument vitrectomy technique through the pars plana. Secondary procedures included vitrectomy, lentectomy, scleral buckling and dissection of preretinal membranes. In a follow-up period ranging from 1 to 53 (average 14) months the overall salvage rate (final visual acuity 6/60 [20/200] or better) was 46%. Four eyes were enucleated.
Ocular hypotony associated with detachment of the ciliary body without evident cyclodialysis has been corrected by reattachment of the ciliary body to the sclera. This was achieved by suturing the ciliary body to sclera under microscopic control. It would seem that prolonged hypotony of this type can be cured by this method.
Fourteen patients underwent surgery for macular pucker. The maximal follow-up is 26 months, the minimum is 3 months, and the average is 10 months. The essential feature of the operation is mechanical separation of the posterior cortical vitreous from the retinal surface. A fine wrinkling retinopathy usually remains. Visual recovery, although usually incomplete, is significant and has been maintained throughout the entire period of observation.
The bone CO2 buffering system and bone calcium and phosphorus were studied in guinea pigs exposed to 1% CO2 for periods up to 8 wk and killed at weekly intervals together with control animals of the same age. Measurements were made of arterial CO2 tension, pH, standard bicarbonate, and bone Ca and P. Heat-stabile bone CO2 (carbonate) was determined as dry bone CO2 and heat-labile bone CO2 (bicarbonate) as delta wet-dry bone CO2. During the first 3-4 wk of exposure to 1% CO2, a systemic acidosis was found as indicated in a lowered pH, increased arterial CO2 tension, and decreased standard bicarbonate. The acidosis subsided during the last 4 wk of exposure. Phasic changes in bone bicarbonate were observed as shown in immediate rise lasting for 2 wk followed by a 2-wk decline and second rise after 6 and 8 wk. Bone carbonate exhibited the opposite change during the first 4 wk and thereafter remained stable at an elevated level. Bone Ca and P fell in association with increasing bone bicarbonate and rose with increasing bone carbonate.
Twelve eyes of 10 patients with type I Irvine-Gass syndrome underwent pars plana vitrectomy after cystoid macular edema had been present a mean of 13 months and showed no evidence of resolving spontaneously or, in some cases, of responding to laser photocoagulation or steroid therapy. The disorder appears to resolve spontaneously in an average of 16 months. Following vitrectomy the edema resolved clinically in 10 of the 12 eyes, in an average of 3.7 months, and the visual acuity improved significantly in 8 of the 12 eyes--in five instances from legal blindness to 20/50 or better. The results suggest that pars plana vitrectomy is of value in the treatment of this disorder.