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.     

Birth control pills and nonprofessional voice: acoustic analyses.

PURPOSE: Two studies are presented here. Study 1 was aimed at evaluating whether the voice characteristics of women who use birth control pills that contain different progestins differ from the voice characteristics of a control group. Study 2 presents a meta-analysis that combined the results of Study 1 with those from 3 recent studies that compared voices of women who use and do not use birth control pills. METHOD: In Study 1, voice samples from 30 women with no history of voice training, who use pills with different progestins (drospirenone, desogestrel, gestodene), and 10 women who do not use the pill were recorded at specific time points across the menstrual cycle and were analyzed acoustically. In Study 2, results from Study 1 were analyzed jointly with results from three recent studies, which used similar methodologies. RESULTS: Results of Study 1 did not reveal acoustic differences in sustained phonation of vowels across the pill groups and controls. Results of the meta-analysis performed in Study 2 indicated that pill users exhibited lower jitter and shimmer values on sustained vowels, whereas no difference of fundamental frequency was observed among women who use the pill. CONCLUSIONS: These results support findings from previous studies, which suggested that no adverse effect on voice was detected among nonprofessional speakers who use new-generation monophasic birth control pills, for the measures studied. Furthermore, results of the meta-analysis suggested that some acoustic properties of the voice, which are reflected in perturbation measures in sustained vowels, may be improved among women who use the pill.     

Use of Vicryl mesh to support the esophageal wall after circular myotomy (Livaditis procedure) in long-gap esophageal atresia — an experimental study

Circular esophageal myotomy (CEM) is currently a well-accepted technique for elongation of the upper esophageal pouch in cases of long-gap esophageal atresia (EA). Esophageal pseudodiverticulum is a frequent and perhaps underreported sequela of this technique, characterized by ballooning or outpouching of the esophageal mucosa in the myotomized area. The present study was designed to seek a supplement for the CEM technique in order to avoid possible pseudodiverticulum formation in the myotomized area. We created an animal model to simulate the anatomic conditions present after primary repair of EA facilitated by CEM. Three groups of dogs underwent either cervical (1 group) or thoracic (2 groups) esophageal myectomy. In the cervical and first thoracic groups, the denuded mucosa was left without any support. In the second thoracic group, the denuded mucosal area was wrapped with polyglactin 910 (Vicryl) mesh. In all three groups the esophagus was narrowed by a Marlex mesh ring 3 cm distal to the myectomized zone, simulating a condition resulting from anastomotic narrowing. The dogs underwent barium swallows under fluoroscopy at different postoperative periods and were killed 4 or 6 months after surgery. The esophagi were removed for gross and radiologic investigation under maximal insufflation as well as for histologic assessment. The proposed canine model proved to be useful for study of the myectomized esophagus, mimicking the anatomy and conditions after CEM in long-gap EA repair. Wrapping the denuded mucosa with Vicryl mesh fortified the weakened esophageal wall, thus diminishing the likelihood of future pseudodiverticulum development. In light of the simplicity of the technique and the absence of any evident risk or complications, we recommend that the use of Vicryl mesh wrap be considered during CEM to reinforce the esophageal wall.Supported by the Slezak Fund for Experimental Surgery (Grant #01370791)     

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.     

Association of psychiatric disorders and sleep apnea in a large cohort

STUDY OBJECTIVES: We conducted the present study to determine whether psychiatric disorders are commonly associated with sleep apnea in Veterans Health Administration beneficiaries. METHOD: The Veterans Health Administration maintains several centralized databases containing healthcare data for more than 4 million veterans. We reviewed data from 1998 to 2001 and identified patient records having International Classification of Diseases-Ninth Edition-Clinical Modification codes indicating sleep apnea and various psychiatric conditions. Subsequently, we compared age, sex, ethnicity, and prevalence of comorbid psychiatric conditions for Veterans Health Administration beneficiaries with and without sleep apnea. RESULTS: Out of 4,060,504 unique cases, 118,105 were identified as having sleep apnea (estimated prevalence of 2.91%). Mean age at the time of diagnosis was 57.6 years. Psychiatric comorbid diagnoses in the sleep apnea group included depression (21.8%), anxiety (16.7%), posttraumatic stress disorder (11.9%), psychosis (5.1), and bipolar disorders (3.3%). Compared with patients not diagnosed with sleep apnea, a significantly greater prevalence (P < .0001) was found for mood disorders, anxiety, posttraumatic stress disorder, psychosis, and dementia in patients with sleep apnea. CONCLUSIONS: Sleep apnea is associated with a higher prevalence of psychiatric comorbid conditions in Veterans Health Administration beneficiaries. This association suggests that patients with psychiatric disorders and coincident symptoms suggesting sleep-disordered breathing should be evaluated for sleep apnea.