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Biomedical subjects

E A Carr

Publications and source records attributed to E A Carr.

At least 37 records · Page 2Linked to original sources

Effect of vitamin D3 on imaging of experimental myocardial infarcts with technetium-99m pyrophosphate: further studies of the role of calcium.

We previously found that a pulse dose of vitamin D3 increased [99mTc]PPi uptake by rat myocardial necrosis. Vitamin D3 raised serum and lesion [Ca] but not, we now report, lesion [Fe]. We now also report that D3 increased [99Tc]PPi uptake by myocardial infarcts (L) in dogs from 0.345 +/- 0.007% administered (kg) dose/g in controls to 0.703 +/- 0.089 in treated (p less than 0.025). Vitamin D3 decreased uptake by dog bone (B) as measured in rib and sternum, increasing L/B from 1.10 +/- 0.23 to 2.30 +/- 0.52 (p = 0.06) X (L) was positively, (p less than 0.005) and uptake by sternum was negatively (p less than 0.05) correlated with serum [Ca] and [P], respectively. Scintigrams graded by a "blinded" observer, showed 4+, 4+, and 3+ infarcts, respectively, in three D3-treated dogs, and 2+, 2+, and 1+, respectively, in three untreated. One untreated and one treated dog were negative; the latter showed the least response to D3 in serum [Ca] and [99mTc] in tissue samples. Vitamin D3 can increase L/B in dogs, enhancing scintigraphic images.

Animals↗

Uptake of technetium-99m methylene diphosphonate by fractured and osteoporotic bone after a pulse dose of vitamin D3.

The effect of a pulse dose of Vitamin D3 on uptake of [99mTc]MDP by fractured and osteoporotic bone, respectively, was compared with D3's effect on uptake by normal bone in rats. At 4, 7, and 14 days, respectively, after femoral fracture, basal uptake was significantly (p less than 0.005) increased at the fracture site by 336.8, 276.1, and 183.5%, respectively, over the contralateral control site. D3-treated rats had lower uptakes than untreated controls at all three fracture sites and at 12 of 15 normal bone sites but analysis of variance showed the uptake differences were not significant. Cortisone-induced osteoporosis caused a significant (p less than 0.05) decrease in basal uptake. The decrease occurred in all nine bone areas studied. D3 caused a significant (p less than 0.05) increase (mean 16.2%) in uptake by these osteoporotic bones, but a significant (0.1 greater than p greater than 0.05) decrease (mean 13.0%) in uptake by the same bones in normal controls. Thus, D3 had an effect on uptake by the bone lesion, osteoporosis, that differed from D3's effect on uptake by fracture or normal bone.

Animals↗

Effect of vitamin D3, other drugs altering serum calcium or phosphorus concentrations, and desoxycorticosterone on the distribution of Tc-99m pyrophosphate between target and nontarget tissues.

Radioactive imaging agents are chemically designed for selective distribution. Another approach to selectivity is to find stable compounds that favorably influence this distribution. Using a rat model of myocardial necrosis, we studied effects of various stable compounds (as a single, large dose or fractionated into short series) on the ratio, uptake of Tc-99m pyrophosphate (PPi) by the target lesion/uptake by the principal nontarget, bone (L/B). Vitamin D3s ability to increase L/B was mediated by the hypercalcemia and hyperphosphatemia that it caused. The hypercalcemia was accompanied by increased [Ca] in the lesion. In contrast, pulse doses of desoxycorticosterone acetate (DOCA) at 7 and 6 hr before killing increased uptake by lesion, increasing L/B from 0.19 +/- 0.03 to 0.45 +/- 0.08 (p less than 0.01), with no change in serum [Ca] and minimal changes in serum [P], [Na], and [K]. DOCA also increased the lesion-to-blood ratio from 6.5 +/- 0.07 to 15.4 +/- 3.9 (p less than 0.05). These results encourage further study of DOCA's effect and investigation of other stable drugs that may influence distribution of other imaging agents.

Animals↗

Studies of uptake of the bretylium analogue, iodobenzyltrimethylammonium iodide, by non-primate, monkey and human hearts.

Uptake of (+/-)-[3H]-noradrenaline, [14C]-bretylium and [125I]-o-iodobenzyltrimethylammonium iodide (RIBA) by rat heart was studied by the Langendorff technique. All three compounds showed significant uptake. 2 Corticosterone and 17-beta-oestradiol inhibited the uptake of all three compounds by rat heart, a finding consistent with extraneuronal uptake (uptake2). 3 [131I]-RIBA was injected intravenously into pigs and monkeys (M. speciosus). Myocardial samples taken from pigs killed 1 and 2 h after injection showed significant uptake. No significant uptake was found in myocardial samples of monkeys killed 10 min, 2 h and 24 h, respectively, after injection. 4 Four normal human volunteers received [125I]-RIBA intravenously and the image of the precordial area was followed by means of scintillation camera for the first 4 h after injection. In two of the subjects, the scintigrams were repeated at 22 and 23 h after injection, respectively. No evidence of myocardial uptake was observed. 5 These results suggest the possibility that man and at least one other primate species may differ from lower species with regard to uptake.

Adult↗

A radioiodinated bretylium analog as a potential agent for scanning the adrenal medulla.

Studies with radioiodinated bretylium analogs (RIBA) suggested that the p-isomer was capable of concentrating in adrenal medulla. The present studies with 125I-p-RIBA in rats and dogs confirm this property and show its marked and persistent affinity for the adrenal medulla. Analogous studies with 14C-p-IBA indicate that it is the quaternary form of the drug that is retained by the adrenal and that high thyroidal radioactivity following 125I-p-RIBA administration is due to in vivo deiodination of the drug.

Adrenal Gland Diseases↗

Panel 2: phase II investigations.

At the end of Phase II, a decision must be made as to whether or not the drug should be developed as a therapeutic agent. Such a decision may be based on many criteria in addition to the scientific data derived from the Phase II study. At this point, expert judgment is needed. One should like to assume that if the decision is made to proceed with the increasingly expensive and laborious process of further development, the drug will, barring some completely unforeseen misadventure, ultimately find its way into clinical therapeutics. Phase II studies, therefore, are the most crucial stage in the course of drug development. Planning of these studies requires great care and investigators of the highest caliber should be used for their conduct. The escalating costs of new drug development are resulting in an undesirable imbalance of efforts in the direction of studies characterized more by easily defined end points than by therapeutic needs. Industry, academia, and the FDA must all be concerned with facilitationg studies in areas of most-needed therapeutic advances.

Clinical Trials as Topic↗

Energy reserves in transplanted and sham-operated carciac tissue=.

Tissue levels of creatine phosphate (CP), creatine, adenosine-triphosphate(ATP), inorganic phosphate (Pi), glycogen, glucose and lactate were determined in heterotopically transplanted and recipient hearts as well as in the myocardium of sham-operated rabbitsmthe ATPase activity in these tissues was also estimatedmthe results revealed no biochemical indication of ischemic conditions in the transplanted organs relative to the other investigated tissue. The tissue levels of CP in the donor heart were even higher then in both the recipient and sham-operated organs. The concentrations of the other above listed compounds in all the studied tissue were similar throughout the first 5 post-operative days. The effect of surgery was manifested in decreased levels of CP, still prevailing 3 days post-operative in all of the investigated tissue. However, on the fifth day after surgery, the tissue concentration of CP showed a trend toward recovery. The activity of Na,K-ATPase in both donor and recipient hearts was similar. One day after surgery, the activity of the Mg-ATPase was 27% lower relative to its value on days 3 and 5 post-operatively. However no correlation was obtained between the change in Mg-ATPase and tissue concentrations of ATP.

Adenosine Triphosphatases↗