Behavioral tolerance to and withdrawal from multiple fluoxetine administration.

The objective of this study was to characterize the lasting effects of fluoxetine on the locomotor behavior of rats using a computerized activity-monitoring system. Challenge dosages (8, 16, and 24 mg/kg i.p.) of fluoxetine 2 h into the dark phase resulted in dose-dependent suppression of locomotor activity for 4 h following injection. Escalating (10-30 mg/kg i.p.) semidaily fluoxetine administration for the next five days resulted in decreasing locomotor activity during the multiple-administration period relative to saline control. Circadian activity patterns at the conclusion of the regimen were unchanged in shape, but featured uniform decreases in locomotor activity at every hour which were more significant during the phase. Upon discontinuation, fluoxetine-treated rats showed a significant increase in activity during the first 4 h following the first "missed" dose which was not seen in subsequent washout. Ninety-six h after the final maintenance dose, the initial three dosages were readministered, and the locomotor activity suppression in response to the rechallenge dose of fluoxetine was significantly lessened compared to initial challenge. These findings suggest that tolerance and withdrawal were obtained.

Bone mineral mass associated with postmenopausal vertebral deformities.

Vertebral morphometry on thoracic and lumbar spine radiographs and bone mass measurements were carried out on 215 patients investigated for postmenopausal osteoporosis. Bone mineral mass was measured on the central third of the skeleton by neutron activation analysis and the result, normalized for body size, expressed as a calcium bone index (CaBI). The normal CaBI value for females (20-40 years) is 0.97 (0.11) with a lower limit for these young, normal women, of 0.75. Vertebral compression deformity was defined as a mean height more than 15% lower than adjacent normal vertebrae. Thoracic and lumbar anterior wedge deformities and central compression were defined as anterior/posterior (A/P) or mid/posterior (M/P) height ratios of less than 0.75. For the 129 patients without vertebral deformities, the mean CaBI was 0.80 (0.12) (1 SD) and 32% of these patients had CaBI values below the normal young adult range (CaBI less than 0.75). In 20 patients, vertebral deformities were limited to 1 or 2 mid-thoracic vertebrae, and the mean CaBI values for these 20 patients was 0.81 (0.15), equal to that for patients without any vertebral deformity. For the remaining 67 patients, (i.e., patients with one or more vertebral deformities involving at least one distal thoracic or one lumbar vertebra) the mean CaBI value was 0.66 (0.10), 17% below the value for patients without vertebral deformities. Low CaBI values (CaBI less than 0.75) were observed in 87% of these patients, consistent with the diagnosis of osteoporotic fractures. Based on our CaBI results, however, mid-thoracic deformity was not associated with significant osteopenia and is not, therefore, diagnostic of osteoporotic fracture.

Role of resting thallium201 perfusion in predicting coronary anatomy, left ventricular wall motion, and hospital outcome in unstable angina pectoris.

We performed quantitative thallium scintigraphy in 66 unstable angina patients, 5.6 +/- 5.1 hours after rest pain, to predict coronary anatomy, left ventricular wall motion, and hospital outcome. Thallium defects and/or washout abnormalities were present in 5 of 10 (50%) patients with coronary stenoses less than 50%, 27 of 33 (82%) patients with coronary stenosis greater than or equal to 50% and no history of previous myocardial infarction, and in 23 of 23 patients (100%) with histories of previous infarction. Defects were uncommon in the territory of vessels with less than 50% (13 of 61, 21%), but significantly more common in the territory of vessels with greater than or equal to 50% stenosis (57 of 137, 42%), p less than 0.005. With the addition of washout abnormalities to defect analysis, sensitivity for detection of coronary stenoses improved to 67% (92 of 137), p less than or equal to 0.005, but specificity fell to 59% (36 of 61), p less than 0.01. Segmental wall motion abnormalities were less common in segments with normal perfusion (21%) or in those with washout abnormalities alone (19%), than in segments with thallium defects (45%, p less than 0.005). Defects in patients with previous infarction were common in both segments, with normal (26 of 66, 40%) or abnormal (24 of 45, 53%) wall motion. Eleven of 18 patients with in-hospital cardiac events, but no history of myocardial infarction, had resting thallium defects, whereas only 8 of 25 patients without cardiac event had thallium defect (p = 0.056).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic morphology in unstable angina pectoris.

Complex morphology occurs frequently in unstable angina; however, its relation to symptomatic presentation, timing of angiography and hospital outcome has not been investigated. Accordingly, coronary angiography was performed 5 +/- 2 days after qualifying rest pain in 101 consecutive patients presenting with acute coronary insufficiency (n = 67) or crescendo angina (n = 34). Significant coronary artery disease was defined as any greater than or equal to 50% stenosis, and complex morphology as any stenosis with irregularity, overhang or thrombus. Eight of the 67 patients presenting with acute coronary insufficiency later proved to have a myocardial infarction as the qualifying event (creatine kinase twice normal with elevation of MB fraction). There were no myocardial infarctions in the crescendo angina group. Complex morphology occurred in 61% of patients. Thrombus alone occurred in 27% of patients with unstable angina without myocardial infarction, with similar frequencies between the 2 clinical groups. In contrast, intraluminal thrombi were identified in 78% of patients with acute coronary insufficiency who later proved to have a myocardial infarction as the qualifying event. The need for urgent catheterization (less than 48 hours) prompted by recurrent symptoms was associated with the angiographic findings of intraluminal thrombus (46%) and complex morphology (83%). The presence of complex morphology and intracoronary thrombus was associated with a higher incidence of in-hospital cardiac events, i.e., revascularization, myocardial infarction and death, independent of the incidence of multivessel disease.

Measurement of the trunk musculature of active males using CT scan radiography: implications for force and moment generating capacity about the L4/L5 joint.

The purpose of this study was to add to the growing database of cross-sectional areas and moment arm lengths of trunk musculature using the methods of computerized tomographic scanning. An attempt was also made to estimate muscle force and moment generating capacity under various reported values of muscle force per unit cross-sectional area. The data were obtained on 13 active men 40.5 +/- 11.9 years of age, 173.8 +/- 5.9 cm tall and 89.1 +/- 11.7 kg body mass. Transverse CT scans were taken at the level of the L4/L5 disc with the subjects supine. Muscle cross-sectional areas were measured from 35 mm slides of the scans using a planimeter and moment arm length in the transverse plane were taken from the centroid of the L4/L5 disc to the centroid of the muscle section. Prior to estimating force and moment generating capacity, areas were corrected, where necessary, for fibre pennation angle to produce a physiological cross-sectional area. The physiological cross-sectional areas (cm2) for one side of the body were (mean +/- S.D.): sacrospinalis (SS) 15.9 +/- 2.5; multifidus (Mu) 4.2 +/- 0.7; psoas (Ps) 17.6 +/- 4.0; rectus abdominis (RA) 7.9 +/- 2.5; external oblique (EO) 9.4 +/- 2.7; internal oblique (IO) 8.1 +/- 2.3; transverse abdominus (TA) 2.9 +/- 1.3. The anterior posterior moment arm lengths were: erector mass (SS and Mu combined) 5.90 +/- 0.52; Ps 0.58 +/- 0.40; R.A. 10.28 +/- 2.07; E.O. (anterior portion) 5.94 +/- 1.39; E.O. (posterior portion) 2.08 +/- 1.39; I.O. (anterior portion) 6.92 +/- 1.63; I.O. (posterior portion) 3.85 +/- 1.54. The corresponding lateral moment arm lengths were: 3.26 +/- 0.36; 4.88 +/- 0.36; 4.35 +/- 1.31; 12.86 +/- 1.93; 13.95 +/- 1.16; 10.77 +/- 2.02; 12.52 +/- 1.26. The maximum force per unit cross-section that human muscles are capable of generating is not well defined. However, assuming an intermediate value of 50 N cm-2 of physiological cross-section, the erector musculature observed at the L4/L5 level should be capable of generating an extensor moment of about 118 N.m. At a muscle stress of 30 or 90 N cm-2, values also reported on human muscle, the moment would be 71 and 213 Nm, respectively. It must be remembered, however, that muscles not observable at the L4/L5 level can create moments around that center of rotation.(ABSTRACT TRUNCATED AT 400 WORDS)

Localization of pheochromocytoma by selective venous catheterization and assay of plasma catecholamines.

The diagnosis of pheochromocytoma rests primarily on determination of the 24-hour urinary excretion of catecholamines and their metabolites. In most cases nephrotomography and selective arteriography or venography, or both, are sufficient to localize the tumour. Selective venous catheterization and the assay of plasma catecholamines should be considered for pheochromocytoma localization in: (a) patients in whom standard techniques fail to localize the tumour; (b) patients who exhibit idiosyncratic reactions to the angiographic contrast materials; (c) young patients or patients with familial pheochromocytoma, including those with multiple neurofibromatosis or multiple endocrine adenomatosis, type 2; (d) patients with recurrent, malignant, or suspected multicentric or extra-adrenal tumours; and (e) patients excreting only norepinephrine in the urine. The validity of the results is particularly dependent on the skill with which venous catheterization is carried out.

Variations in x-ray exposures to patients.

X-ray exposures to patients were measured in 30 rooms in Toronto hospitals. For a given procedure, the total exposure for a satisfactory examination differed from one room to another by as much as a factor of 30, skin exposures reaching 90 R and more for barium enemas and barium meals. The factors primarily responsible for these large differences in exposure were fluoroscopic exposure rate (0.65-12 R/min) and time 1.5-12 min), kVp and filtration (8:1), choice of screen-film combination (6:1) and attenuation of table tops and phototimers (4:1). The increase by a factor of 5 in exposure of pelvic organs, when using beams directed AP instead of PA, requires that remote-controlled GI machines be used cautiously, particularly on women of childbearing age. It is also important that these machines have tables with low attenuation. The use in some rooms of minimal fluoroscopic exposure rates and 70 mm fluorography at total exposures of less than 5 R shows that radiographic examinations can be made virtually "safe" with modern, properly adjusted equipment.

Parathyroid carcinoma: location of pelvic metastases by parathyroid hormone assay.

A metastasis from a functioning parathyroid carcinoma was located by PTH radioimmunoassay and selective venous catheterization. The site of the metastasis, verified at autopsy, was in the right side of the pelvis. This is the most distant reported location for metastatic parathyroid carcinoma. The patient's plasma immunoreactive PTH rose more than twofold in response to induced hypocalcemia. This suggests that relative hypocalcemia, induced therapeutically in such patients, may result in a higher chronic level of PTH secretion.