Evaluation of aplastic anemia with indium chloride In 111 scanning.

Twenty-one patients (12 male, nine female) with diverse causes of aplastic anemia underwent indium chloride in 111 bone marrow scintigraphy. Good correlation of the scan interpretation with other clinical values, including the peripheral blood counts and bone marrow biopsy, was found in 25 of the 26 studies. These encouraging results with a noninvasive procedure that permits evaluatin of the entire bone marrow organ suggest a broader use for indium bone marrow scintigraphy in aplastic anemia.

Changes in circulating iodothyronines in euthyroid and hyperthyroid subjects given ipodate (Oragrafin), an agent for oral cholecystography.

A dose (3 g) of sodium ipodate used routinely in oral cholecystography caused a fall in serum 3,5,3'-triiodothyronine and a rise in serum 3,3',5'-triiodothyronine in three patients taking thyroxine (T4), four euthyroid subjects,and four hyperthyroid patients. Serum T4 fell in patients with hperthyroidism, whereas it rose in the other two groups. Sodium ipodate appears to alter peripheral T4 metabolism and, in addition, produces thyroid-inhibiting effects in hyperthyroidism.

A radioimmunoassay for measurement of 3,3'-L-diiodothyronine (T2).

A sensitive, specific and reproducible radioimmunoassay (RIA) for measurement of 3,3'-L-diiodothyoride (T2) in concentrated ethanol extracts of serum and amniotic fluid is described. The T2 binding antiserum was prepared aby immunization of rabbits with T2-human serum albumin conjugate. Of various thyroid hormone derivatives tested, only 3-L-monoiodothyonine cross-reacted significantly with T2 binding sites on the antiserum...

Thermal marrow expansion: effect of temperature on bone marrow distribution.

The distribution of bone marrow in adult mammals is limited mainly to those bones deeply embedded in the body and subject to the higher core body temperature. Active marrow is much less prevalent in the limbs. In the past this was attributed to the lower temperature of the peripheral bone marrow. We have studied the possibility of stimulating hematopoiesis in the limbs (and tails) by increasing the limb temperature. This has been done by elevating the ambient temperature of mice and by tail implantation techniques. Mice incubated at ambient temperature of 22 degrees C can be "expanded" to have markedly enhanced marrow activity in the limbs by either incubation for seven days or more at 34 degrees C, or by implantation of the bone into core temperature areas (peritoneal implantation). The increase in marrow activity is shown both histologically and by 59Fe uptake techniques. Anemia does not enhance this effect, indicating a local phenomenon. A variety of experiments suggest that temperature per se and not temperature-induced increase in blood flow is involved. The increase in marrow activity is accompanied by a modest local increase in clonogenic marrow stem cells but it cannot be shown for certainty whether the phenomenon of Thermal Marrow Expansion (TME) is due to the local effect of elevated temperature on stem or stromal cells. The erythrocytes produced by TME appear normal by in vivo fragility testing. TME may have clinical usefulness in man if the phenomenon occurs in the same fashion as rodents.

Antihypertensive activity of 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives.

A series of 51 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives was prepared and evaluated for antihypertensive activity in the conscious spontaneously hypertensive rat. A number of these compounds, notably 6-(2,6-dichlorophenyl)-2-methylpyrido[2,3-d]pyrimidin-7-amine (36), lowered blood pressure in these rats in a gradual and sustained manner to normotensive levels at oral doses of 10-50 mg/kg. Normalized blood pressure levels could then be maintained by single daily oral doses. The effect of structural variation in the 6-aryl group and in the 2 and 4 positions of the pyridopyrimidine ring on activity is reported and discussed.

Antihypertensive activity of 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives. 2. 7-Acyl amide analogues.

The effect of acylation with a variety of acids on the antihypertensive activity of 6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidine-7-amine (1) is reported, and structure-activity relationships are discussed. Although several of the compounds show good oral antihypertensive activity in the conscious, spontaneously hypertensive rat (SHR), their activity profile appears to differ from 1 in that the onset of action is shortened at comparable blood pressure lowering doses, and the magnitude of effect is considerably greater at higher doses. A variety of urea, thiourea, guanidine, and amidine analogues also were prepared. Although many of these derivatives showed some antihypertensive effects when dosed orally to SHR, this activity was weaker and of shorter duration than that obtained with 1. Aqueous solubilities and hydrolytic stabilities for four of the more active compounds were measured and suggest that these do not function as prodrugs of 1.

Synthesis and structure-activity relationships of potent new angiotensin converting enzyme inhibitors containing saturated bicyclic amino acids.

The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfhydryl and non-sulfhydryl ACE inhibitors to give compounds equipotent to captopril and enalapril both in vitro and in vivo. Structure-activity relationships are discussed. Compound 11a (CI-907, indolapril) has advanced to clinical evaluation.

Lymphoscintigraphy with Tc-99m-labeled dextran.

Current agents for lymphoscintigraphy have limitations because of slow migration of the colloidal tracers from the injection site and the unknown effect of phagocytosis on the removal of the labeled particles. The usefulness of Tc-99m dextran (TcDx) with a molecular weight of 110,000 has been tested for lymphoscintigraphy. Computer-assisted dynamic imaging and serial blood sampling in 13 dog experiments demonstrated that the tracer cleared only by lymph drainage from an interstitial injection site. Following interdigital injection of 1.0 ml (0.5-5.0 mCi), TcDx reached the knee or elbow lymph nodes in 12.4 +/- 6.5 (1 s.d.) sec, and the inguinal or axillary lymph nodes in 98.0 +/- 42.3 sec. It cleared from the injection site with a half-time of 31.5 min. In a dog with surgically induced lymphedema, tracer migration was markedly delayed in the edematous leg and the radionuclide lymphoscintigram resembled the contrast lymphangiogram. Initial studies in man yielded high-quality radionuclide lymphograms of the leg, and the pelvic and paraaortic lymph nodes. We conclude that TcDx is very promising for lymphoscintigraphy.

A noninvasive procedure for in vivo assay of a lung amine endothelial receptor.

Lung endothelial N-isopropyl-p-iodoamphetamine (IMP) binding sites were assessed applying principles of competitive binding assay adapted for in vivo measurements obtained by digital imaging. Data were acquired following the method published by Rahimian et al., a modification of the dual indicator dilution technique of Chinard and Crone. Iodine-123 (123I) IMP, the test cellular tracer, and technetium-99m (99mTc) dextran, the reference vascular tracer were imaged during their first pass through the superior vena cava, right heart, lungs, and left heart in West African dwarf goats. The lung fractional extraction of IMP diminished progressively from 0.96 to 0.20 as the amount of IMP in the test tracer boluses was gradually increased from 0.6 to 150 mg. This demonstrated that lung extraction of IMP is by way of a saturable binding system, presumably receptors. The dissociation constant of IMP-lung binding sites reaction was calculated by Scatchard plot and found to be 11.7 mg. The amount of IMP bound at saturation (R), was found to be 30 mg. Assuming that a single molecule of IMP bound a single receptor, the total number of free receptors was computed as the Avogadro's number times R, divided by the IMP molecular weight, and found to be 6.04 X 10(19). Using a computer model, it was determined that the 20 mg per bolus isotherm was the most sensitive for measuring the number of total free receptors (binding sites). This is the first time, to our knowledge, that noninvasive in vivo assessment of receptors in lung has been accomplished. Basically, the method used can be applied in humans and, also, to assess receptors in organs other than the lungs.

Measurement of metabolic extraction of tracers in the lung using a multiple indicator dilution technique.

Selective pulmonary uptake of many natural and synthetic substances has been demonstrated by physiologists and pharmacologists using isolated perfused lung preparations or invasive techniques. It is difficult, however, to relate these laboratory studies to disease processes and to the study of problems encountered in a clinical environment. Our goal was to develop a noninvasive method for studying the pulmonary uptake of tracer substances using available radiotracers, gamma cameras, and computers that would give information similar, if not identical, to that from the invasive laboratory methods, and that could be applied in a clinical setting. The multiple-indicator dilution technique, modified for external counting, is well suited for such studies of pulmonary uptake of tracer substances. In this study, Tc-99m micro sulfur colloid (Tc-99m micro SC) was used as an intravascular reference tracer, N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) as a cellular test tracer amine, and In-111 DTPA as an extracellular tracer. Calculated first-pass lung uptakes of I-123 IMP and In-111 DTPA were 0.92 +/- 0.04 and 0.17 +/- 0.04, respectively, relative to the reference tracer. Using this approach, the first-pass pulmonary extraction of a variety of radiolabeled test tracers can be measured in a clinical environment in a variety of physiologic settings.

Cutaneous lymphoscintigraphy in malignant melanoma.

Melanoma commonly metastasizes to the regional lymph nodes. With early melanomas the accepted therapy is local wide excision and regional lymphadenectomy for nodes in the lymph drainage path. For some melanoma sites the lymph node groups that should be removed are obvious; however, for other sites the decision as to which nodes are at risk may present a difficult problem, since drainage from these sites may vary unpredictably from classical anatomic descriptions. We reviewed recent reports from four institutions using four radiocolloids (colloidal 198gold, 99mtechnetium antimony sulfur colloid (99mTcSbSC), 99mtechnetium sulfur colloid (99mTcSC), and micro 99mtechnetium sulfur colloid (micro 99mTcSC)) to determine lymph shed from melanomas. Correlation with surgical findings was excellent. In addition, drainage to second and third nodal groups, some of which were not clinically predictable, was frequently observed. While all four agents gave good scans, 99mTcSC and micro 99mTcSC are probably the best radiopharmaceuticals.

Linoleate produces remission in canine mycosis fungoides.

Linoleic acid (LA) administered orally as safflower oil (SFO), which is 76% LA, produced remission in 6 out of 8 dogs with mycosis fungoides (MF). Following each feeding of SFO on 5 successive days to a normal dog peak plasma levels of non-esterified (free) LA in excess of 200 microM were observed. No clinical toxicity was observed from the SFO feedings in the normal or MF animals at the levels of SFO (3 ml/kg) used in these studies. However, a marked rise in white blood cells (WBC) and lymphocytes and a marked transient drop in the serum glutamine transaminases SGOT and SGPT was noted both in the normal and MF animals. These effects of LA may be significant for the remission of MF.

The lung as a metabolic organ.

Recently, the lung has received increasing attention as a metabolic organ. In this role, the lung modulates the composition of the arterial blood by several mechanisms: removing active substances from the plasma, releasing substances into the plasma, temporarily holding substances from circulation, and activating or inactivating substances that pass through the lungs. In this report, the procedures proposed by different investigators for in vivo noninvasive assessment of the lung metabolic functions are reviewed. Most procedures are based on an estimation of the clearance of plasma amines by the lung endothelial cells. This clearance is assessed by measuring the lung uptake or the extraction fraction of an intravenously (IV) injected radiolabeled amine. Our own procedure, which assesses the number of free pulmonary endothelial amine receptors, is discussed in detail. In our procedure, the number of receptors was computed using the number of injected molecules of amine and determining the lung extraction fraction of the amine during its first pass through the lungs. In goats, using N-isopropyl-p-iodoamphetamine labeled with 123I as the radiopharmaceutical, the total number of endothelial lung amine receptors was found to be 1.589 X 10(20). The methods for studying the lung metabolic functions, which are discussed in this report can be applied in humans to evaluate either physiological or pathological conditions.

Immunoreactive and receptor-active insulin-like growth factor-I (IGF-I) and IGF-binding protein in blood plasma from the freshwater fish Macquaria ambigua (golden perch).

The presence of insulin-like growth factor-I (IGF-I)-related molecules and IGF-binding factors in blood from golden perch, Macquaria ambigua, an Australian native freshwater fish, was investigated. Serum was acidified to dissociate IGF and IGF-binding protein complexes that might be present, and fractionated by size-exclusion high-performance liquid chromatography at pH 2.8. Fractions were neutralized and their activities assessed by (i) an immunoassay for mammalian IGF-I which also detects chicken IGF-I but in which all known forms of IGF-II react very poorly, (ii) a receptor assay for IGF-II in which all known forms of IGF-I react poorly, and (iii) a type-I IGF receptor assay in which mammalian IGF-I and IGF-II polypeptides are amost equivalent. No IGF-II-like activity was detected. Three peaks of IGF-I-like activity were detected by IGF-I immunoassay and type-I IGF receptor assay. The major peak of activity was similar in molecular size to human IGF-binding protein-3, 45-55 kDa ('large IGF'), and a minor peak of activity which was similar in size to mammalian IGFs, 7.5 kDa. A third peak of activity was observed eluting at a time which indicates that it is a smaller molecule than any previously described IGF. The large IGF was temperature-sensitive, but was not a binding protein for 125I-labelled human IGF-I (hIGF-I). This material therefore was able to bind to anti-hIGF-I antibodies and to human type-I IGF receptors, and may represent the fish equivalent of mammalian prepro-IGFs.(ABSTRACT TRUNCATED AT 250 WORDS)

Radionuclide photoscanning. Usefulness in preoperative evaluation of melanoma patients.

The results of radionuclide scans (liver, bone, and brain scans and whole-body scans using bleomycin tagged with radioactive indium [111In]) performed on 100 melanoma patients during their initial evaluation were reviewed to determined whether or not they effected a change in clinical staging or therapeutic decision. Patients were classified as stage I (primary disease) or stage II (regional disease) on the basis of regional lymph node dissections. Only one patient (stage II) of 73 stage I and II patients had an abnormal finding on the initial radionuclide scan. Fifteen of 26 patients thought to be stage III (disseminated disease) on clinical grounds had abnormal findings on at least one scan. A therapeutic change as a result of scanning occurred in the stage II patient after abnormal bone and whole-body scans. As an initial routine screening test for stage I and II melanoma patients, radionuclide scanning was unproductive and rarely influenced therapeutic decisions.

Postirradiation protection of chromosomes by linoleate.

Physiological concentrations of linoleate reduce the frequency of micronuclei and chromosome aberrations in mouse bone marrow cells in vivo and of micronuclei in human lymphocytes in vitro when administered one hour after exposure of the cells to gamma rays.

Assessment of first-aid knowledge and decision making of high school athletic coaches.

OBJECTIVE: To assess the first-aid knowledge and decision making of interscholastic athletic coaches exposed to athletic injuries. DESIGN AND SETTING: Survey demographic information, First- Aid Assessment, and Game Situation Data Sheet in 17 metropolitan high schools. SUBJECTS: A total of 17 metropolitan high schools participated in this study, and 104 athletic coaches completed questionnaires. Fifteen different athletic sports were represented in this investigation. Thirty coaches (29%) worked with more than one athletic sport during the year. Male subjects constituted 83% (n = 85) of the sample. Years of coaching experience ranged from first-year coaches to those with more than 28 years of experience. Most coaches (61%, n = 63) investigated were teachers, and the remaining subjects were walk-on coaches. MEASUREMENTS: Central tendency scores were determined in the demographic analysis. x(2) analyses were performed to determine the interaction between First-Aid Assessment and the Game Situation Data. RESULTS: Thirty-eight (36%) of the 104 athletic coaches tested achieved passing scores of 29 or higher, with the total scores ranging from 19 to 34. For the Game Situation Data Sheet, 75% (n = 78) of the coaches selected the same response to 7 questions. Most coaches in this study chose to return injured players to the game. We analyzed the data to determine whether coaches who passed the First-Aid Assessment responded differently than those who did not. (The scenario presented in one question involved a starting player's sustaining injury when losing a close game.) Coaches who passed the First-Aid Assessment tended to return injured starters to the game, whereas those who failed it kept injured players out of the game. x(2) analysis on the second question (the team is winning a close game when a regular player is injured) showed no tendency for passing or failing coaches to respond differently. CONCLUSIONS: The athletic coaches did not adequately meet first-aid standards as established for this study in accordance with the American Red Cross. In addition, coaches who passed the First-Aid Assessment tended to return an injured starter to the game, whereas those who failed decided to keep the player out of the game. It is critical that an unbiased, objective professional person provide all medical care on the athletic playing field, preferably one who is certified in athletic training.

Population-focused research: a broad-based survey of teens' attitudes, beliefs, and behaviours.

Population-focused research and practice is the cornerstone of community health nursing. A population group which is at significant risk for a number of health problems is adolescents. In this article, a report is given of a descriptive study of 2347 high school students, 15-19 years of age. These teens were largely from rural communities in the province of Newfoundland, Canada. They were surveyed to identify their attitudes, beliefs, and behaviours in a variety of life spheres. Results show friendship to be of primary importance to teens. Family also plays a key role in their lives. Relationships with adults, in general, are troubled. Significant gender differences emerged: for example, males are more open than females to causal sex, are more likely to use alcohol and to be more physically active than females; females value family life more, and have more difficulty in the area of self-esteem than their male counterparts. Teens' attitudes reflect many values of Canadian society at large, such as hard work, success and the importance of a good education. The data from this study emphasizes the need for community health programs for teenagers which take into account key characteristics of this target group. This research is a model for compiling data on any population group in the community. Such a model is portrayed as an effective and efficient means of providing baseline information crucial to the delivery of health strategies with specific population groups in the community.