Bone marrow regeneration following fractionated radiation therapy.
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Biomedical subjects
Publications and source records attributed to D C Price.
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Simultaneous 111In-DPTA and metrizamide CT cisternography correlated closely in the qualitative imaging of cerebrospinal fluid (CSF) dynamics in 9 normal patients and in 11 patients thought to have communicating hydrocephalus. CSF clearance of both tracers was similar; significant absorption occurred in the spinal dural sac. Although delayed elevated serum iodine levels correlated highly with abnormal persistent ventricular penetration (detection at 48 hours), these levels cannot be used to predict abnormal ventricular stasis. The pattern of ventricular and cortical sulcus enlargement on the plain CT scan did not indicate whether the dynamic metrizamide cisternogram would be normal or abnormal.
Bromide and sucrose distributions were measured as functions of time after tracer injection into 14 rat organs that accounted for 93% of body wt, with the goal of evaluating the use of bromide and sucrose as tracers for the extracellular water volume (ECW). The tracers, Na, 82Br, 125I-labeled human serum albumin, [14C]sucrose, and 3H2O, were used to calculate bromide and sucrose content in red cells, plasma, and 13 blood-free organs. Selective concentration of Br- occurs in RBC, stomach, and skin, accounting in part for the discrepancy between the Br- space and the smaller ECW volume as derived from other methods. Sucrose is rapidly metabolized in the rat and its 14C tracer cannot be used for ECW determination in this species. The kinetics of Br- distribution were estimated in rats and in 16 human subjects by measuring plasma disappearance values and specific organ uptakes. A pharmacokinetic compartmental model was derived, containing explicit parameters for blood flow, diffusion constants, and ECW spaces separately for each organ. Precise fitting of experimental bromide data was achieved for the rat; satisfactory fitting was also achieved in man from more limited plasma and biopsy data.
Surgical preparation of rats for micropuncture resulted in a marked decrease in sodium excretion (UNaV) compared to awake animals. Associated with surgery, hematocrit (Hct) rose. Studies were performed to determine whether the rise in Hct resulted from reduced plasma volume (PV) or increased red cell volume (RCV) and to explore the relation of such alterations to the fall in UNaV. PV and RCV were determined in the calm awake rat using 125I-albumin and 51Cr-labeled red blood cells. Micropuncture surgery was performed and RCV, PV, and Hct again measured. After anesthesia and femoral artery catheterization, Hct was not different from Hct in awake animals (42.9 +/- 2.8%). The Hct increased following surgery to 48.2 +/- 2.8% (P less than 0.001), accompanied by a large fall in PV (-18.9 +/- 2.3%, P less than 0.001) with no change in RCV. Plasma volume repletion to awake values restored UNaV toward levels appropriate for dietary intake in animals on a high salt diet. Althouth plasma repletion slightly increased UNaV above awake values in low salt diet rats, they continued to avidly retain salt with respect to total salt load.
Oral submucosal blood flow was measured at dental injection sites in anesthetized dogs and compared with subcutaneous blood flow. Blood flow was calculated from the measured half-time for clearance of radioactive xenon dissolved in saline. By this method, oral submucosal blood flow was much greater than subcutaneous blood flow and was comparable in magnitude to values reported for cerebral blood flow. Injection of a solution containing 1:100,000 epinephrine at the mandibular canal produce a delayed clearance of isotope which was three times as long as the clearance time for solutions without epinephrine.
Two methods for Ga-67 citrate imaging were compared on 20 patients. Scans were performed using approximately equal procedure time with two instruments: (A) a dual 5-in. rectilinear scanner with medium-energy collimator, with a single window spanning both the 93-keV and the 185-keV spectral peaks; and (B) a large-field (15-in. diam) Anger camera equipped with moving table, medium-energy collimator, and three windows covering the 93-keV, 185-keV, and 300-keV peaks separately. Sixteen abnormal sites and 24 normal sites were selected for comparison. Each site was evaluated by four physicians experienced in interpreting Ga-67 citrate images. The observers performed significantly better using the images obtained with the large-field camera (three windows) than with the dual 5-in. scanner (single window).
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Several parameters of body composition were measured in eight men before and after 14 days of continuous recumbency, and in eight women before and after 17 days of recumbency. The parameters measured included body weight, body water, body potassium, plasma volume, and plasma protein concentrations. From these, values were derived for body fat content, lean body mass, body cell mass, and circulating plasma proteins. In general, the men and women responded similarly to continuous recumbency. Characteristically, there was significant reduction of plasma volume and body potassium in both groups. The women showed a significant reduction in circulating plasma protein, entirely in the albumin fraction; a similar change was observed in the men. The women, but not the men, showed a significant increase in circulating fibrinogen. Both men and women lost body cell mass, while body fat content remained the same or tended to increase slightly. It is expected that similar changes would occur in weightlessness. It is further concluded that women should tolerate the weightlessness of space flight physiologically as well as men.
Nonradioactive cesium, as an analogue of potassium, has been used to label autologous red blood cells for determination of the red cell volume in man. The initial and the equilibration concentrations of cesium are assayed by fluorescent excitation analysis (FEA), using a 600 mCi 241Americium source and a Si(Li) detector with a 1024-channel analyzer. Comparative studies with 51Chromium in 13 rabbits showed good correlation, but the intracellular cesium concentration achieved by simple incubation with 2.6 per cent cesium chloride solution was too low to be of practical value in humans. Incubation of the human red blood cells with 50 mug per milliliter of Nystatin in 2.6 per cent cesium chloride opened reversible "pores" in the red cell membrane which permitted high intracellular cesium labeling without demonstrable red cell damage. The cesium red cell volumes in 11 random human subjects differed from the 51Chromium red cell volumes by only 0.2 +/- 4.5 per cent and 2.5 +/- 7.6 per cent at blood sampling times of 10 minutes and 40 minutes, respectively. Blood cesium levels fell with a clearance half-time of 31.5 hours in 4 rabbits, and 2.4 days in 1 normal human. Fluorescent excitation analysis of cesium-labeled autologous red blood cells permits accurate determination of the red cell volume in man without associated patient radiation, thus making the procedure much more acceptable for children, pregnant women, normal volunteers, and for repeated studies in the same individual.
The bromide dilutional volume determined by intravenous administration of 82Br has been compared with the corresponding volume determined by oral administration of stable bromide in 11 patients with various medical disorders. Stable bromide was assayed by fluorescent excitation analysis using a 109Cd source and a lithium-drifted silicon detector. The average deviation between the fluorescent and the radiobromide dilutional volumes was 4.2% with a standard deviation of +/- 8.5%. This substantiates both the accuracy of the fluorescent excitation method as applied to this tracer and the validity of utilizing oral tracer administration in comparison with intravenous administration. The derived estimates of extracellular fluid volume averaged 28.7% of body weight in the entire group of 11 patients and 25.8% in the 4 normal subjects included in the group. Evaluation of the extracellular fluid space utilizing fluorescent excitation of stable bromide permits high statistical accuracy of sample measurement with great simplicity compared with current chemical methods and with avoidance of the patient radiation exposure associated with 82Br.
Renal scintiphotography with (131)I-hippurate was the primary diagnostic procedure in evaluating renal failure and complications in over 500 transplant patients. This diagnostic test has become our principal method of evaluation and followup of renal transplants, especially in the early post-transplant period. It has accurately distinguished tubular necrosis, rejection, and other complications in the post-transplant period. Its simplicity, safety and accuracy are of great value to transplant surgeons and their patients.
Hemoglobin and myoglobin are a major source of dietary iron in man. Heme, separated from these hemoproteins by intraluminal proteolysis, is absorbed intact by the intestinal mucosa. The absorbed heme is cleaved in the mucosal cell releasing inorganic iron. Although this mucosal heme-splitting activity initially was ascribed to xanthine oxidase, we investigated the possibility that it is catalyzed by microsomal heme oxygenase, an enzyme which converts heme to bilirubin, CO, and inorganic iron. Microsomes prepared from rat intestinal mucosa contain enzymatic activity similar to that of heme oxygenase in liver and spleen. The intestinal enzyme requires NADPH; is completely inhibited by 50% CO; and produces bilirubin IX-alpha, identified spectrophotometrically and chromatographically. Moreover, duodenal heme oxygenase was shown to release inorganic (55)Fe from (55)Fe-heme. Along the intestinal tract, enzyme activity was found to be highest in the duodenum where hemoglobin iron absorption is reported to be most active. Furthermore, when rats were made iron deficient, duodenal heme oxygenase activity and hemoglobin-iron absorption rose to a comparable extent. Upon iron repletion of iron-deficient animals, duodenal enzyme activity returned towards control values. In contrast to heme oxygenase, duodenal xanthine oxidase activity fell sharply in iron deficiency and rose towards base line upon iron repletion. Our findings suggest that mucosal heme oxygenase catalyzes the cleavage of heme absorbed in the intestinal mucosa and thus plays an important role in the absorption of hemoglobin iron. The mechanisms controlling this intestinal enzyme activity and the enzyme's role in the overall regulation of hemoglobin-iron absorption remain to be defined.
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