Spontaneous resurgence of conditioned fear weeks after successful extinction in brain injured mice.

Mild traumatic brain injury (TBI) is a major risk factor for post-traumatic stress disorder (PTSD), and both disorders share common symptoms and neurobiological defects. Relapse after successful treatment, known as long-term fear resurgence, is common in PTSD patients and a major therapeutic hurdle. We induced a mild focal TBI by controlled cortical impact (CCI) in male C57BL/6 J mice and used fear conditioning to assess PTSD-like behaviors and concomitant alterations in the fear circuitry. We found for the first time that mild TBI, and to a lesser extent sham (craniotomy), mice displayed a spontaneous resurgence of conditioned fear when tested for fear extinction memory recall, despite having effectively acquired and extinguished conditioned fear 6 weeks earlier in the same context. Other characteristic symptoms of PTSD are risk-taking behaviors and cognitive deficits. CCI mice displayed risk-taking behaviors, behavioral inflexibility and reductions in processing speed compared to naïve mice. In conjunction with these changes there were alterations in amygdala morphology 3 months post-trauma, and decreased myelin basic protein density at the primary lesion site and in distant secondary sites such as the hippocampus, thalamus, and amygdala, compared to sham mice. Furthermore, activity-dependent brain-derived neurotrophic factor (BDNF) transcripts were decreased in the prefrontal cortex, a key region for fear extinction consolidation, following fear extinction training in both TBI and, to a lesser extent, sham mice. This study shows for the first time that a mild brain injury can generate a spontaneous resurgence of conditioned fear associated with defective BDNF signalling in the prefrontal cortex, PTSD-like behaviors, and have enduring effects on the brain.

Quantification of walking exercise required for improvement of dipyridamole thallium-201 image quality.

Dipyridamole 201Tl imaging is an accepted diagnostic procedure for the evaluation of patients unable to perform adequate treadmill exercise, but is limited by high infradiaphragmatic activity. While recent studies have shown that the addition of exercise reduces this activity, the amount of exercise needed to effect such an improvement is uncertain. To prospectively evaluate the amount of walking exercise required to produce improvement in image quality, 120 patients were randomized to either a control group receiving dipyridamole alone, or to dipyridamole supplemented with one of four exercise protocols. Ratios of heart-to-liver and heart-to-adjacent infradiaphragmatic activity were generated from anterior images acquired immediately following the test. Heart-to-total infradiaphragmatic activity was also graded semiquantitatively. Results showed improved target-to-background ratios as well as semiquantitative assessment of image quality for dipyridamole supplemented with exercise as compared to dipyridamole alone. No difference was seen between walking in place and Bruce treadmill exercise at Stage 0 or 0.5. A trend towards higher values was seen with Bruce Stage 1 exercise supplementation, but this did not reach statistical significance. No significant complications occurred during the study. We conclude that 3 min of walking exercise is a safe and effective means of improving the quality of dipyridamole 201Tl images.

Effect of exercise supplementation on dipyridamole thallium-201 image quality.

To determine the effect of different types of exercise supplementation on dipyridamole thallium image quality, 78 patients were prospectively randomized to one of three protocols: dipyridamole infusion alone, dipyridamole supplemented with isometric handgrip, and dipyridamole with low-level treadmill exercise. Heart-to-lung, heart-to-liver, and heart-to-adjacent infradiaphragmatic activity ratios were generated from anterior images acquired immediately following the test. Additionally, heart-to-total infradiaphragmatic activity was graded semiquantitatively. Results showed a significantly higher ratio of heart to subdiaphragmatic activity in the treadmill group as compared with dipyridamole alone (p less than 0.001) and dipyridamole supplemented with isometric handgrip exercise (p less than 0.001). No significant difference was observed between patients receiving the dipyridamole infusion, and dipyridamole supplemented with isometric handgrip exercise. We conclude that low-level treadmill exercise supplementation of dipyridamole infusion is an effective means of improving image quality. Supplementation with isometric handgrip does not improve image quality over dipyridamole alone.

Evaluation of myocardial perfusion by thallium-201 imaging at rest and during exercise. Comparison with ECG stress testing.

In order to assess the accuracy of thallium-201 cardiac imaging at rest or during exercise in detecting permanent or transient myocardial damage, we studied 49 patients with angiographically documented coronary disease (31 with previous myocardial infarction) and 29 patients with normal coronary arteries. The resting thallium scan was significantly more accurate in detecting previous myocardial infarction (31 patients) than the resting ECG (22 patients) (P < 0.01). The combination of thallium imaging and ECG stress testing revealed reversible myocardial ischemia in 41 of the 49 patients (84%), compared with 28 of 49 (57%) detected by ECG stress testing alone (P < 0.01). Thallium imaging was more accurate in ruling out coronary disease (26 of 29 patients, 90%) than ECG stress testing (19 of 29 patients, 65%) (P < 0.05). In patients with previous myocardial infarction, thallium imaging alone or in combination with ECG stress testing was not significantly more sensitive than ECG stress testing alone.

Radionuclide assessment of aortocoronary bypass surgery.

Rest and exercise thallium 201 myocardial scintigraphy and multiple gated radionuclide angiography were correlated with the results of clinical status, exercise electrocardiography, coronary arteriography, and contrast left ventriculography in a series of 12 prospectively studied consecutive patients before and after aortocoronary bypass operation. Patients were divided into two groups based on a comparison between preoperative and postoperative 201T1 scintigrams. Group 1 (6 patients) demonstrated improved or normal postoperative perfusion scintigrams and excellent correlation between the site of a patent graft and the improvement in myocardial perfusion on the postoperative exercise scintigrams. Regional wall motion remained normal in 3 patients and improved in 3. In Group 2 (6 patients) the postoperative 201T1 scintigrams were unchanged or worse. Each patient demonstrated graft occlusion, graft stenosis, distal disease, or a perioperative myocardial infarction. No improvement in regional wall motion occurred in 4 of these 6 patients. Neither the symptomatic response to aortocoronary bypass operation nor the response to exercise testing successfully predicted graft patency.

Blood pressure characteristics of a select group of North American males, followed for 20 years.

This report describes the 20-year blood pressure behaviour of 3869 selected young North American males.Initial mean systolic and diastolic pressures were higher than those recorded five years later; after that pressures increased progressively. The effect of initial selection was evident for the first 10 years of exposure.A significant relationship was demonstrated between all initial systolic and diastolic levels and the 20-year blood pressure behaviour. Systolic pressure was not affected by age until age 50 and diastolic until age 45. After that a significant relationship was demonstrated.In 20 years multiple readings >/= 140 and/or >/= 90 mm. Hg were recorded in 26% of the population. Increases in pressure usually extended over many years. Commonly they were labile, fluctuating above and below 140/90 mm. Hg. In a small, clearly defined group, accelerated increases reached high levels in three to 10 years.