Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.     

Angiotensin I-converting enzyme inhibitor improves reactive hyperemia in elderly hypertensives with arteriosclerosis obliterans.

Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. Blood flows of the forearms and legs were measured by strain-gauge plethysmography. The vasodilatory response to the release of compression of the forearms and thighs at 200 mmHg or 20 mmHg more than systolic blood pressure for 5 min and to sublingual administration of nitroglycerin (0.3 mg) was assessed. The maximum reactive hyperemic flow in 35 legs with arteriosclerosis obliterans was significantly (p < 0.001) decreased compared to the value in legs in the control hypertensive subjects. Moreover, maximum reactive hyperemic flow in the forearms of patients with arteriosclerosis obliterans was significantly (p = 0.002) decreased compared to that in the control subjects. Blood pressure was similarly decreased by treatment with temocapril or amlodipine. Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.     

Quantitative analysis of regional wall motion and thickening by quantitative gated SPECT: comparison with visual analysis

PURPOSE: Electrocardiograph-gated myocardial SPECT permits a quantitative assessment of global and regional functions by quantitative gated SPECT software. To validate quantitative indexes of wall motion and wall thickening, the authors compared these indexes with visual scores. MATERIALS AND METHODS: Gated myocardial SPECT was performed 60 minutes after the administration of Tc-99m sestamibi at rest in 42 patients with coronary artery disease. Regional wall motion (measured in millimeters and wall thickening (expressed as a percentage) were calculated by quantitative gated SPECT software in nine left ventricular myocardial segments and the results were compared with the five-point visual score interpretations of cinematic display. RESULTS: A high correlation of wall motion was observed between the quantitative and visual analyses (r = 0.810; P < 0.001). In addition, a high but somewhat less significant correlation of wall thickening was observed between the quantitative and visual analyses (r = 0.606; P < 0.001). CONCLUSIONS: In conclusion, regional wall motion and wall thickening can be evaluated quantitatively by electrocardiograph-gated myocardial SPECT and quantitative gated SPECT software. This will be useful for functional assessments made with various interventions.     

Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (SS554), in mice

The antitumor effect on Meth-A fibrosarcoma in BALB/c mice of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (designated as SS554), was examined. Only intratumoral injection had a curative effect; subcutaneous, per oral, or intravenous routes had no such effect. The co-presence of an oily vehicle has been shown to be necessary for antitumor activity of a natural cord factor. When SS554 was examined in suspensions of sesame oil, squalane, squalene or sesame oil and water emulsion, a 60% cure rate was achieved. However, no such effect was obtained with a suspension in Tween-PBS or a solution. It should also be noted that sequential but independent administrations of SS554 and oil were found to be as effective as the simultaneous administration of oil and SS554 in emulsion form. In the case of the emulsion, the amount of sesame oil necessary was over 10%, or 0.01 ml in absolute terms. Cures were obtained in a dose-dependent manner by injection of SS554 in amounts in excess of 1 mg. The effect of the time of administration was also examined; the best result was obtained when intratumoral injection was done on day 3 after tumor implantation. Mice cured by SS554 exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific; it did not extend to a rechallenge with RLmale-1 leukemia cells.     

Suppressive effects of minocycline on the pituitary-thyroid axis in humans

Minocycline has been thought to induce “black thyroid”, a condition marked by discoloration due to brown deposits. However, its effect on thyroid function in humans is still obscure. We conducted a prospective study of thyroid hormone levels in 17 patients who were administered 200 mg minocycline daily for 10 days. We found that minocycline significantly reduced the serum total thyroxine level (8.43±0.61 to 7.09±0.45 μg/dl, mean ± SEM;P<0.01), and free thyroxine level (1.12±0.10 to 1.01±0.08 ng/dl, mean ± SEM;P<0.01). There was also a slight, but insignificant, elevation of thyroid stimulating hormone (TSH) in patients treated with minocycline. Similar suppression of thyroxine and free thyroxine was not observed in control patients treated with β-lactam and/or aminoglycoside antibiotics. Risk factors for the reduction in these thyroxine levels included age and a high serum baseline level of free thyroxine. We found a significant correlation between the free baseline thyroxine level and a reduction in free thyroxine after minocycline administration (Y=0.420X−0.377, r=0.597;P<0.01). Despite the observed alterations, the serum levels of all thyroid hormones after minocycline therapy were still within the normal range. This antibiotic does not appear to induce clinical hypothyroidism, yet given the results of this study, we would like to recommend pituitary-thyroid axis monitoring during the use of this antibiotic.     

Antithrombotic therapy for stroke prevention in patients with atrial fibrillation

Atrial fibrillation(AF) is a common arrhythmia that is an important independent risk factor for stroke. The overall risk of stroke in AF patients averages about 5%/y, but with wide variation depending on the presence of coexistent thromboembolic risk factors, which include increasing age, history of hypertension, previous stroke or transient ischemic attack(TIA), and diabetes. AF patients with prior stroke or TIA are at highest risk(about 12%/y). Adjusted-dose warfarin(target INR 2.0-3.0) is highly efficacious for preventing stroke in AF patients, and is safe for selected patients. Aspirin has a modest effect on reducing stroke. Warfarin is recommended for high-risk AF patients who can safely receive it. Aspirin may be indicated for those with a low stroke risk and for those who cannot receive warfarin.     

The guideline how to use the antimicrobial agents--the guidance how to use the antimicrobial agents

In regard to reconsider the way of antimicrobial agent, it has given the guideline which is how to use the antimicrobial agent to be protected the occurrence of drug resistant bacteria and how to use it safety. This writing omit the way of thinking about the proper use, the safety use, and the prevention for hospital acquired infections by this reference. What the proper use for antimicrobial agent is. The basic idea as the proper use for antimicrobial agent is 1. to heal a patient(individual-defense), 2. not to increase drug resistant bacteria(group-defense), 3. to be utilizable for a medical resource mostly. In the choice of antimicrobial agent for the individual situation, we have to think about 1. (to heal a patient) seriously first, and then, of course, we recognize the point of view for 2. and 3. has a good balance in this way.     

Improvement in fatty acid utilization in relation to a change in left ventricular hypertrophy in spontaneously hypertensive rats

Although fatty acid metabolism is reportedly impaired in myocardial hypertrophy, it is unclear whether the antihypertensive drugs are associated with improved fatty acid metabolism. In order to evaluate the effects of antihypertensive drugs on fatty acid metabolism and myocardial perfusion, the simultaneous uptake of iodine-125(125I)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and thallium-201 (Tl) were measured in 3 groups of rats: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR chronically treated with captopril (SHR-C), and (3) SHR chronically treated with hydralazine (SHR-H). Captopril and hydralazine were administered to their respective groups for 3 weeks from 12 weeks of age. The hearts were removed 10 min after simultaneous intravenous injections of BMIPP and Tl and the 125I and 201Tl counts were measured to calculate the uptake ratio. The systolic blood pressure (SBP) in SHR-N was 222+/-10 mm Hg, whereas the SHR-C and SHR-H groups showed significant SBP reduction (156+/-11, and 158+/-10 mm Hg, respectively) (p<0.01 each). The heart/bodyweight ratio was significantly lower in SHR-C (2.48+/-0.09) than in SHR-N (2.74+/-0.11) (p<0.05). However, there was no significant difference in the heart/bodyweight ratio between SHR-N and SHR-H (2.65+/-0.09). The ratio of BMIPP uptake to Tl uptake (BMIPP/Tl) was significantly higher in SHR-C (0.71+/-0.13) than in SHR-N (0.50+/-0.09) (p<0.05). However, BMIPP/Tl in SHR-H (0.53+/-0.09) was similar to that in SHR-N. These results suggest that captopril improves fatty acid metabolism in the hypertrophied ventricle in SHR. The metabolic alterations may improve with left ventricular hypertrophy regression but are not effected by the reduction of blood pressure only.