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A joint project between the Human Monitoring Laboratory (HML) and the Ottawa Hospital has measured the retention of 131I in patients who have received the radioiodine diagnostically. Thirty-nine subjects with intact thyroid glands and nine athyreotic subjects were measured in the HML's whole-body/thyroid counter to determine the retention of 131I following its medical administration. The average biological half-life of 131I in 26 euthyroid subjects was found to be 66.1+/-6.3 days which may he statistically significantly lower than the ICRP recommended value of 80 days. Nine hyperthyroid patients had a mean biological half-life of 38.2+/-8.6 days and in three hypothyroid patients the corresponding value was 29.3+/-8.8 days. Thyroid 131I uptake was measured in a conventional clinical fashion at the Ottawa Hospital Civic campus 24 h after oral administration of the radioiodine using a collimated thick sodium iodide detector placed over the neck anteriorly. Measured values were 10.144+/-0.009, 0.314+/-0.035 and 0.045+/-0.010 of the administered dose in euthyroid, hyperthyroid and hypothyroid patients respectively. The euthyroid range at the hospital is 0.06 - 0.22. Uptake was significantly lower for the euthyroid group than the ICRP value of 0.3. The radioiodine retention in athyreotic subjects followed a two compartment model with biological half-lives of 1.0+/-1.2 days and 18.4+/-1.1 days.

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OBJECTIVE: Stress modulates gut function, but whether the type of stressor influences colonic motor activity is unclear. The motor patterns and regional variations are also poorly understood. Our aim was to determine the effects of psychological and physical stress on colonic motility. METHODS: Ambulatory colonic manometry was performed by placing a six-sensor probe up to the mid-transverse colon, without sedation, in 12 healthy subjects. Five hours later, a dichotomous listening test (psychological stress) was performed, which was preceded by listening to a narrative passage (control); recovery entailed listening to relaxing music (1 h each). Subsequently, intermittent hand immersion in cold (4 degrees C) water (physical stress) was performed, preceded by hand immersion in warm (37 degrees C) water (1/2-h each). Colonic pressure activity and cardiovascular responses were measured throughout the study. RESULTS: When compared with the control period, both stressors induced a greater number of pressure waves (p < 0.05), and the area under the curve (p < 0.01), but only physical stress increased (p < 0.05) pulse rate and blood pressure. There were no regional differences in colonic motility. During recovery, the motor activity returned to baseline after physical stress, but remained high after psychological stress. Psychological stress induced more (p < 0.05) propagated contractions, whereas physical stress induced more (p < 0.05) simultaneous contractions. CONCLUSIONS: Both stressors enhanced colonic motor activity, but psychological stress induced a prolonged response with propagated activity and without appreciable autonomic response. Thus, colonic motor responses may vary depending on the stressor.

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Monte Carlo simulations have been performed to evaluate the design of collimated detectors used to measure 125I or 131I in the thyroid gland. Two detector sizes were simulated for each radioisotope: (i) for 125I monitoring 2.54 cm diameter and 7.62 cm diameter and 0.2 cm thickness and (ii) for 131I monitoring 2.54 cm diameter, 3.2 cm thickness and 7.62 cm diameter, 6.4 cm thickness. The virtual thyroid gland was 20 g. Activity was placed in both the gland and the remainder of the body in varying amounts to assess the efficacy of collimation. The results show that the detector should be sufficiently large so that its solid angle of acceptance when placed 15 cm anterior to the skin surface will include the whole of a moderately enlarged thyroid gland. Heavy collimation to reduce the contribution of extrathyroidal radioiodine within the subject's body is not normally required. It may be of more value as a positioning device and spacer ensuring an appropriate and constant neck to detector distance than in cutting down counts from extrathyroidal activity. In specifying a sensitive detector system for monitoring intrathyroidal radioiodine, a wide angle of acceptance and sufficient detector crystal thickness take precedence over collimation and shielding.

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OBJECTIVE: To determine the effect of ioxaglate and ioversol on glomerular filtration rate (GFR) in a heterogeneous inpatient group to allow calculation of the necessary sample size for a randomized trial. PATIENTS AND METHODS: The study group consisted of 36 men and 12 women, ranging in age from 25 to 79 (mean 63) years. Fourteen of the patients, those undergoing abdominal aortography with or without renal arteriography, received ioxaglate (Hexabrix 320; 40 to 240 [mean 141] mL), and the remaining 34, those receiving intravenous injections and those undergoing computed tomography with arterioportography or carotid arteriography, received ioversol (Optiray 320; 20 to 180 [mean 87] mL). GFR was measured by determining the clearance of diethyl-enetriaminepenta-acetic acid labelled with technetium-99m up to 72 hours before and 24 hours after administration of the contrast medium. Risk factors for nephrotoxicity included diabetes (7 patients) and pre-existing renal impairment (mild in 11 and severe in 6). RESULTS: GFR decreased by 20% to 34% in six patients (13%); in only one of these was the serum level of creatinine increased at 24 hours. One of these six patients had received 120 mL of ioversol for carotid arteriography and had no risk factors for nephrotoxicity. The other five had received 40 to 187 (mean 115) mL of ioxaglate, three for abdominal aortography and two for selective renal arteriography. The risk factors in these patients included diabetes (two patients) and severe pre-existing renal impairment (two patients). Renal failure necessitating treatment did not develop in any of the patients. CONCLUSIONS: A decrease in GFR occurred more often with ioxaglate than with ioversol and usually occurred in patients with additional risk factors. Injection of contrast medium into the abdominal aorta or the renal artery may increase the risk of nephrotoxicity. Changes in serum level of creatinine at 24 hours were not reliable in identifying patients with decreased GFR. On the basis of these data, the authors estimate that a group of 194 patients would be necessary for a randomized trial comparing the nephrotoxicity of ioxaglate and ioversol for abdominal aortography.

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Certain inhalational diseases show a predilection for a particular region of one or the other lung that may be related to the site of deposition of inhaled particles. We conducted inhalation studies with monodispersed aerosol particles in 22 healthy student volunteers to determine how deposition varied between the two lungs. Ventilation lung scans were obtained with the subjects seated in front of a gamma camera while breathing radiolabelled particles. Subsequently we made paired comparisons of the radioactivity deposited in corresponding regions of the right and left lungs. Although regional differences in deposition between the left and right lung were often statistically significant, they were not always consistent between individuals. Particle deposition and the degree of penetration differed between the two lungs with there being generally more deposition in the perihilar region of the right lung. We suggest that the anatomy of the central airways may influence the pattern of deposition, thereby introducing disparities in particle deposition between the two lungs. The present findings lend support to experimental lung cast data and to the concept that anatomical differences between the two lungs influence the site of deposition.

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A simple method of precisely administering a compact gas bolus during selectable portions of the inspiratory cycle was developed to examine certain fundamental attributes of lung physiology and ventilation. The method allows for a small, well-defined bolus to be delivered during different phases of inspiration in a precise fashion. A pneumatically driven three-way switching valve is synchronized to the breathing pattern and controls the interjection of radioxenon boli in the inspiratory stream, spiking a small portion of the inhaled breath. The 133Xe dispersion and redispersion in the lungs is mapped and the clearance followed. Regional differences are analysed to determine how ventilation might influence the development of lung diseases due to inhaled toxins. Scintillation imaging at 20 frames s-1 allows near real-time characterization of the ventilation distribution. Novelty comes from the application of fast data gathering, the flow through valve design for delivery of tightly compacted boli and from tracing different fractions of the breath. The procedure involves low radiation exposure. An apparatus and method for acquiring data on lung filling and emptying not previously available is described. Potential applications are identified which may allow the re-examination of orthodox lung physiology.

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Based upon the known high toxicity and high antagonist activity of t-butylorthobenzoates towards the GABA receptor complex, 4-t-butyl-1-(4-iodophenyl)-2,6,7-trioxabicyclo[2.2.2]octane 5 and its radioiodo analogues ([123I]-5 and [131I]-5 were prepared as potential markers for the gated chloride channel of GABAA receptors. Mice showed rapid clearance of [131I]-5 from all organs including the brain. The radioactivity was found to proceed into the urine in spite of the high lipophilicity of 5, the high binding affinity of 5 for plasma protein and the apparent chemical stability of 5 in plasma.

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Three N-methylcarbamates of iodonitrobenzyl alcohols (4-iodo-2-nitrobenzyl alcohol 2, 5-iodo-2-nitrobenzyl alcohol 3 and 4-iodo-2,6-dinitrobenzyl alcohol 4) bearing [125I] have been prepared and characterized for their lipophilicity, their reduction potentials and the in vivo liability of the radioiodine in healthy mice. Based upon these results, 2 and 4 were tested in tumour-bearing mice showing limited uptake of radioactivity in tumours and a tumour-to-blood ratio of less than 1. Consequently these particular carbamates are not satisfactory as hypoxia imaging agents.

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Bone scintigraphy is used to detect radiographically silent fractures. Magnetic resonance imaging (MRI) is currently used to screen knee injuries for cartilage and ligament damage. MRI also delineates bone marrow and fractures. We investigated the bone scintigraphic findings in patients who had subchondral bone injuries demonstrated on MRI. Thirteen patients underwent MRI, three-phase bone scintigraphy with SPECT, and arthroscopic surgery after sustaining acute traumatic hemarthrosis of a knee. They all had clinically unsuspected subchondral bone injuries demonstrated on MRI with normal radiographs and normal overlying articular cartilage at arthroscopy, consistent with occult fractures. All showed focal bone repair on scintigraphy. Two of the 13 patients showed additional bone injuries only on bone scan. Two other patients scintigraphically showed focal bone repair at the medial femoral condyle due to avulsion of the medial collateral ligament. SPECT was easier to interpret than multi-view planar imaging. Bone scintigraphy confirms subchondral fractures demonstrated on MRI but also demonstrates ligament avulsion injuries and additional more subtle bone injuries.

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Both geometrical isomers (E and Z) of an aminotamoxifen (2) have been prepared as precursors of the corresponding E and Z iodotamoxifens (1). The ability of E and Z-1 and 2 to compete with [3H]estradiol for estrogen receptors in rat uterine cytosol was measured relative to Z-tamoxifen and estradiol. The four tamoxifen derivatives showed affinities ranging from 50% to 1600% of that of tamoxifen. Under the same conditions, tamoxifen's relative binding affinity was 0.2% of that of estradiol. Preparative routes to the radioiodo-tamoxifens, [131I]-E and Z-1, were also developed and provided approximately 100 MBq of 'no carrier added' material in 40-60% radiochemical yield. Study of the biodistribution of these radioligands in tumor-bearing mice demonstrated significant radioactivity in the tumors and in the uterus. For [131I]-E-1, target to background ratios reached 28 for uterus/blood and 10 for tumor/blood; corresponding optimum ratios for [131I]-Z-1 were 10 and 5. A washout study using estradiol indicated selective uptake in the uterus of Swiss white mice. However, tumor uptake and image contrast in humans following intravenous administration of either [131I]-E or Z-1 were insufficient to allow diagnostic use of the radioiodotamoxifens.

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Two patients who had suffered subrachnoid hemorrhage were subjected to intensive monitoring of parameters of circulating blood flow, cardiovascular dynamics, and fluid and electrolyte balance. Among the parameters studied were red cell volume, plasma volume, and total blood volume, cardiac output, and central venous and pulmonary capillary wedge pressures. Both patients experienced acute neurological deterioration during the study. Red cell volume fell in a premonitory fashion prior to neurological deterioration in both, and in one patient plasma volume and total blood volume decreased by almost 50% in the 5 days prior to neurological deterioration. Central venous and pulmonary capillary wedge pressures fell initially but did not predict the deterioration. Systemic vascular resistance fell prior to clinical deterioration in one patient following ventriculoperitoneal shunting, and in the other following craniotomy and subarachnoid drainage. The falls in systemic vascular resistance may have caused shunting of cardiac output away from the compromised cerebral circulation, thereby triggering neurological deterioration.

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As a result of the intrapleural pressure gradient that exists in the human lung, both ventilation and particle deposition increase from apex to base. Since the intrapleural gradient varies with the height of the subject, it was decided to compare regional particle deposition in tall, short, and obese subjects to ascertain whether it was influenced by height and weight. Surprisingly, deposition in the vertical plane was not significantly influenced by the height of the subject when corrected for ventilated lung volume. In addition, it was shown that in obese subjects there was increased deposition in the middle zones relative to the apices and bases. This finding persisted after correction for ventilated lung volume and differential attenuation resulting from non-uniform thickness of the fat layer in the obese subject's chest. In the tall and short groups there was a consistent pattern in the concentric deposition of particles with there being a gradient from the central or hilar region to the periphery of the lungs, with the latter showing the most deposition.

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Patients with ankylosing spondylitis may uncommonly develop apical fibrobullous lung disease, the cause of which is unknown. It is postulated here that rigidity of the thoracic cage leads to reduced apical clearance of inhaled particles and may thereby predispose to chronic infection. Deposition and clearance of inhaled technetium-99m sulphur colloid particles were studied in eight male patients with ankylosing spondylitis who had chest wall rigidity (mean (SD) chest expansion 1.8 (1.07) cm) but normal chest radiographs. As a reference population eight healthy male volunteers were also studied. Particle deposition showed an increasing gradient from apex to base, with no significant difference between patients and controls. Clearance was assessed by comparing absolute counts, corrected for decay, at 24 hours with the baseline values. No delay in particle clearance in those with ankylosing spondylitis was apparent.

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The effect of varying particle size on the site of deposition of inhaled particles in the human lung was measured in 11 young healthy male subjects. The simultaneous inhalation of two chemically inert, radiolabelled particles, differing in size but in no other respect, controlled for all other variables including airways geometry, breathing pattern and posture. Under conditions of quiet respiration the larger particles (3.5 microns) were preferentially deposited in the upper rather than the lower zones of the lungs as compared with the smaller particles (1.1 microns). Furthermore, the penetrance of the larger particles beyond the mucociliary escalator was greater for 3.5 microns particles in all lung zones and particularly at the apex. These findings may be of significance in the pathogenesis of those diseases induced by the inhalation of particles, vapours or fumes.

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We performed 38 cerebral perfusion studies in 33 patients with brain death or with severe central nervous system injury using technetium-99m hexamethyl-propyleneamine oxime [( 99mTc]HM-PAO). Uptake by the cerebrum and/or cerebellium was present in all patients who were not clinically brain dead (ten studies) although the study was often abnormal. In those patients who were brain dead, 16/17 studies demonstrated no uptake in either the cerebrum or cerebellum. In patients suspected of brain death, but who had conditions interfering with the diagnosis the test demonstrated no uptake in 9/11 studies, confirming brain death. A radionuclide angiogram (RNA) of the head was also performed in 33/38 studies and showed complete agreement with the [99mTc]HM-PAO uptake, except in one case. We conclude that cerebral perfusion imaging with [99mTc]HM-PAO is a simple, noninvasive and reliable test to confirm brain death. By comparison with conventional technetium agents, [99mTc]HM-PAO is not dependent on the quality of the bolus injection, is easier to interpret and allows evaluation of posterior fossa blood flow.

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Eighteen lean adult volunteers with insulin-requiring diabetes mellitus attempted to achieve normoglycemia using continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) in a randomized crossover trial of 68 +/- 2.5 weeks (mean +/- SEM) duration. As reported (Diabetes Care 8: 447-55, 1985) the group with absent to low beta-cell function (C-peptide negative, n = 11) attained mean post-absorptive normoglycemia only during CSII vs CIT (p less than 0.05). Only following CSII was this without change in post-absorptive serum triglyceride concentrations (-4 +/- 5.6 vs 12 +/- 4.7 mg/dl; -0.04 +/- 0.6 vs 0.14 +/- 0.05 mM, p less than 0.05) or body weight (0.01 +/- 0.02 vs 0.05 +/- 0.01 kg/week, p less than 0.05). In the group with glucagon stimulated serum C-peptide 100-400 pmol/L (C-peptide positive) responses to CSII or CIT were equal. As total daily insulin dosage (0.05 +/- 0.04 U/kg/day) was the same under all conditions, to explain the efficacy of CSII, glucoregulatory hormone responses were examined. Pre- and post-test breakfast serum free immunoreactive insulin and plasma glucagon concentrations were essentially unaffected by C-peptide or treatment status. Erythrocyte 125I-insulin binding was decreased in the C-peptide negative group only during CSII (8.6 +/- 0.5 vs 10.1 +/- 0.7%, p less than 0.005); C-peptide positive group receptor binding was consistently low (8.2 +/- 0.8, 8.4 +/- 0.9%). During CIT using intermediate-acting insulin post-lunch peripheral venous insulin failed to rise (p less than 0.05), but in the C-peptide positive group, on the basis of C-peptide responses to breakfast an undetected rise and fall of portal venous insulin was assumed to coincide with each meal. Thus, only during CIT in the C-peptide negative group, which received on average 6.4/wk/subject fewer pre-meal regular insulin boluses (p less than 0.01), was the frequency of meal-related change in portal insulinemia decreased. Consistent meal-related fluctuations in portal insulinemia inherent in CSII hepatocytes sensitized by a post-receptor mechanism to the suppressive effects of insulin on glucose output and thus were indirectly responsible for the observed improvement in glycemic control and lipid metabolism in the C-peptide negative group.

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A series of nine radioiodinated quaternary ammonium salts related to phenylcholine were synthesized, characterized, and radiolabeled by exchange. These compounds were evaluated as myocardial perfusion imaging agents in mice, pigs, and humans. Mice biodistribution studies showed that five of the nine compounds were taken up in the heart to the same extent as 201Tl+ at 5 min. At 60 min myocardial retention was significantly better than 201Tl+ for six of the compounds. Several of the compounds showed more favorable heart/blood and heart/liver ratios when compared to 201Tl+. Evaluation of three of the more promising compounds in pigs and humans however revealed no selective myocardial uptake.

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Twenty-three morbidly obese patients underwent gastric emptying studies (Tc-99m egg salad sandwich--a semisolid meal) preoperatively, and at three months and 12 months postoperatively to evaluate the effect of transverse gastroplasty on gastric emptying and to determine the predictive value of this study for weight loss. At three months pouch emptying was variable with nine of 23 patients having prolonged half-times, and 14 shortened half-times compared with preoperative values, despite both groups having identical weight loss. At 12 months pouch half-times returned to baseline. The data suggests that this type of gastroplasty causes weight loss solely by reducing the gastric volume resulting in reduced meal volume. Weight loss is not related to impaired pouch emptying, which might result in a prolonged feeling of fullness. Gastric emptying studies neither preoperatively nor postoperatively have weight loss predictive value for this particular operation.

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