Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome

BACKGROUND: Apical ballooning syndrome (ABS) is a poorly understood clinical entity characterized by acute, transient systolic dysfunction of the left ventricular (LV) apex in the absence of epicardial coronary artery disease and commonly associated with acute emotional stress. We report abnormal regional myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose within 72 hours of presentation with ABS. METHODS: All patients were postmenopausal females, 3 of whom had a major recent life stress event. Coronary angiography revealed no or minimal obstructive epicardial coronary artery disease. All patients exhibited reduced glucose uptake in the mid-LV and apical myocardial segments, which was out of proportion to perfusion abnormalities in half of the cases. CONCLUSION: In all 4 patients, affected regions subsequently recovered regional LV systolic function within 6 weeks.     

Administration of Half-Dose Theophylline Together with Ketotifen to Asthmatic Children—A Double-Blind, Placebo-Controlled Study

Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 μg/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T + K-Placebo (T group); T + K (T + K group); half-dose T + K (T/ 2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T + P, T + K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.     

Suppression of alcohol and saccharin preference in rats by a novel Ca2+ channel inhibitor,Goe 5438

The effect of the novel 1,4-dihydronaphthyridine Ca²⁺ channel inhibitor Goe 5438 (CI-951) on voluntary ethanol consumption was examined in selectively bred alcohol-preferring (P) rats in a free choice two bottle preference test versus water. Intraperitoneally injected Goe 5438 dose-dependently (5, 10 or 20 µmol/kg, twice daily) inhibited ethanol and increased water intake over the 24 h period (injection day). The drug decreased ethanol preference, originally above 90%, by 6%, 19% and 45% at respective doses, on the injection day. That inhibitory effect of the highest dose of Goe 5438 on ethanol preference remained significant also on days 2 and 3 after injections (–51% and –18%, respectively). Goe 5438, in the highest dose, also tended to decrease granulated chow consumption during the injection day only. To further test whether the inhibition of ethanol preference is secondary to decrease in reinforcing properties of ethanol and not due to interference with satiety mechanisms, we compared the effect of two higher doses (10 and 20 µmol/kg, intraperitoneally, twice daily) of Goe 5438 on spontaneous preference for a non-caloric 0.04% saccharin solution in Sprague-Dawley rats. We observed a dose-dependent suppression of preference (by 44% and 58%, respectively) during the injection day, but not the subsequent 24 h period. However, Goe 5438 also significantly alleviated food pellet intake on the injection day. In conclusion, Goe 5438 produces potent and long-lasting inhibition of voluntary ethanol consumption, which may be secondary to attenuation of reinforcing properties of ethanol. Additionally, this particular Ca²⁺ channel inhibitor appears to have mild anorectic properties which may be conducive to acute suppression of alcohol intake.     

Immunological blockade of endogenous thyrotropin-releasing hormone impairs recovery from hyperglycemia in mice

Administration of antiserum to thyrotropin-releasing hormone (TRH) into the lateral cerebral ventricle of mice significantly attenuated recovery from hyperglycemia induced by treatment with 2-deoxyglucose but had no effect on the plasma glucose of saline-treated mice. TRH, injected centrally together with the anti-TRH antibody, reversed the effect of the antiserum and blocked the development of hyperglycemia. These findings suggest that activation of TRH neurons in the central nervous system may be a physiological event influencing recovery from hyperglycemia.     

Unsupervised fuzzy clustering analysis supports behavioral cutoff criteria in an animal model of posttraumatic stress disorder.

BACKGROUND: Unsupervised fuzzy clustering (UFC) analysis is a mathematical technique that groups together objects in the multidimensional feature space according to a specified similarity measurement, thereby yielding clusters of similar data points that can be represented by a set of prototypes or centroids. METHODS: Since clinical studies of mental disorders distinguish between affected and unaffected individuals, we designed an inclusion/exclusion criteria (cutoff behavioral criteria [CBC]) approach for animal behavioral studies. The effect of classifying the study population into clearly affected versus clearly unaffected individuals according to behaviors on two behavioral paradigms was statistically significant. RESULTS: Here the raw data from previous studies were subjected to UFC algorithms as a means of objectively testing the validity of the concept of the CBC for our experimental model. The first UFC algorithm yielded two clearly discrete clusters, found to consist almost exclusively of the exposed animals in the one and unexposed animals in the other. The second algorithm yielded three clusters corresponding to animals designated as clearly affected, partially affected, and clearly unaffected. The algorithm for physiological data in addition to behavioral data failed to elicit discrete clusters. CONCLUSIONS: The UFC analysis yielded data that support the conceptual contention of the CBC and lends additional validity to our previous behavioral studies.     

Inflammatory pseudotumor of the lung — fibrous histiocytoma type

A 7 1/2-year-old girl with an inflammatory pseudotumor of the lung is presented. The nature of the lesion was not recognized pre-or intraoperatively. The lesion was rubbery, yellowish, and well-defined but not encapsulated. Histologically, a spindle-cell lesion with a storiform pattern and chronic inflammatory-cell infiltrate was seen. The immunological and ultrastructural studies supported an inflammatory origin. The lesion corresponds to the fibrous histiocytoma variant of inflammatory pseudotumor of the lung, as defined recently by Matsubara et al. [17]. This must be distinguished from rare benign neoplasms of the lung such as benign fibrous histiocytoma, leiomyoma, Schwannoma, and histiocytosis.     

Histomorphometric analysis of innervation of the anterior cruciate ligament in osteoarthritis

The aim of this study was to determine whether there are quantitative changes in the innervation of the anterior cruciate ligament in osteoarthritis. Eleven whole anterior cruciate ligaments were obtained at autopsy from cadavera of individuals with advanced osteoarthritis; five healthy ligaments were used as controls. The ligaments were transected and stained with hematoxylin and eosin, oil red O for fat, and a modification of Gairn's gold chloride method. The latter stain permits visualization of axons, mechanoreceptors, and free nerve endings that are not apparent on routine stains. The ratio of nerve tissue to periligamentous synovial tissue was determined histomorphometrically by the point-counting method. The nerve tissue was located almost exclusively in the periligamentous synovial tissue. There was a statistically significantly greater area of nerve tissue (as a percentage of the total area) around the anterior cruciate ligaments in the osteoarthritic group than around the ligaments in the control group (p < 0.02). The nerve tissue was distributed evenly throughout the periligamentous synovial tissue in the specimens in both groups. A neurological role has been proposed for the anterior cruciate ligament in osteoarthritis. This study provides morphological evidence for neural pathology of the anterior cruciate ligament in subjects with osteoarthritis.     

Analysis of genomic downsizing on the basis of region-of-difference polymorphism profiling of Mycobacterium tuberculosis patient isolates reveals geographic partitioning

Mycobacterium tuberculosis, the etiological agent of tuberculosis, has lost many coding and noncoding regions in its genome during the course of evolution. We performed region-of-difference (RD) analysis using PCR-based genotyping of 131 M. tuberculosis clinical isolates obtained from four different countries, namely, India, Peru, Libya, and Angola. Our studies revealed that RD patterns are often distinct for strains circulating in specific geographical regions and can be used to trace the descent and spread of an isolate from its original reservoir. We describe our findings, which show that no single isolate from the four countries (n = 131) had all the 15 RDs either deleted or retained. Tuberculosis-specific deletion 1 (TbD1) was found to be conserved in 23% of the Indian isolates, indicating their possible ancient origin. RD9 was the most conserved region, RD11 was predominantly deleted, and RD6 was the most variable among the isolates in our collection irrespective of their geographic region. In contrast to earlier reports, our results demonstrate that the deletion of RD1 does not correlate with a decrease in the virulence potential of M. tuberculosis, as Indian isolates (n = 30) examined by us were from diseased individuals and yet had lost the RD1 region. Our results further illustrated that the intactness of the RD5 region may be associated with increased virulence of the organism. This study highlights that the RDs in M. tuberculosis genomes are geographically distributed and specific and may possibly be associated with virulence spectrum.