Subcutaneous implantation of double velour Dacron into the mouse: infiltration and angiogenesis

An experimental system has been devised for the study of tissue reaction to the subcutaneous implantation of double velour Dacron into the mouse. Animals were given Dacron implants for 3 months, 2 months, 1 month, 3 weeks, 2 weeks and 1 week and the infiltration of the material was assessed using light-microscopy, autoradiography, electron-microscopy and angiography. It was found that the implants became extensively infiltrated with host cells, the response being at a peak in the second and third weeks post-implantation. Macrophages were seen from an early stage, fibroblasts were numerous, and new capillaries penetrated the material. The observations, especially the angiogenic response, are discussed with reference to published information on the actions of the cell types that were seen, in particular the macrophage.     

A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport® and Botox® in the treatment of cervical dystonia

OBJECTIVE—This study was designed toestablish whether a ratio of three units of Dysport^® isequivalent to one unit of Botox^® for the treatment ofcervical dystonia.
METHODS—Patients with predominantly rotationalcervical dystonia, and a minimum of four previous Botox treatments,were randomised to receive either the clinically indicated dose ofBotox or three times that dose in Dysport units. Study botulinum toxinwas administered in a double blind fashion, to one or more clinicallyindicated muscles, at one or more sites per muscle. Patients returnedfor assessment two, four, eight, and 12 weeks after treatment.
RESULTS—A total of 73 patients (Dysport, 38;Botox, 35) were entered. The Dysport group received a mean (SD) dose of477 (131) (range 240-720) Dysport units, and the Botox group receiveda mean (SD) dose of 152 (45) (range 70-240) Botox units. The mean(SEM) post-treatment Tsui scores for the Dysport group (4.8 (0.3)) andthe Botox group (5.0 (0.3)) were not statistically different (p=0.66).The study had 91% power to detect a clinically significant differenceof two points. Both groups showed substantial improvement in Tsui scoreby week 2 (mean (SD); Dysport, 46 (28)%; Botox, 37 (28)%), with apeak effect at week 4 (mean (SD); Dysport, 49 (29)%; Botox, 44 (28)%). A similar response profile was seen for other assessments ofefficacy. The duration of effect, assessed by time to retreatment, wasalso similar (mean (SD); Dysport, 83.9 (13.6) days; Botox, 80.7 (14.4)days; p=0.85). During the study 22 of 38 (58%) Dysport patientsreported 39 adverse events, and 24 of 35 (69%) Botox patients reported56 adverse events (p=0.35). A global assessment of efficacy and safetyconsidered that 29 of 38 (76%) Dysport patients and 23 of 35 (66%)Botox patients were treatment successes (p=0.32).
CONCLUSION—Patients with predominantly rotationalcervical dystonia treated with the clinically indicated dose of Botoxor three times that dose in Dysport units show similar improvements anddo not have significantly different safety profiles.

     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Binding of botulinum neurotoxin to pure cholinergic nerve terminals isolated from the electric organ of Torpedo

Summary Torpedo electric organ has been used to study the binding of botulinum neurotoxin type A to pure cholinergic synaptosomes and presynaptic plasma membrane.¹²⁵I-labeled botulinum neurotoxin type A exhibits specific binding to cholinergic fractions. Two binding sites have been determined according to data analysis: a high affinity binding site (synaptosomes: K_d=0.11±0.03 nM, B_max=50±10 fmol · mg prot^–1; presynaptic plasma membrane: K_d=0.2±0.05 nM, B_max=150±15 fmol · mg prot^–1) and a low affinity binding site (synaptosomes: K_d 26 nM, B_max 7.5 pmol · mg prot^–1; presynaptic plasma membrane: K_d 30 nM, B_max 52 pmol · mg prot^–1). The binding of¹²⁵I-botulinum neurotoxin type A is decreased by previous treatment of synaptosomes by neuraminidase and trypsin, and by a preincubation with bovine brain gangliosides or antiserum raised against Torpedo presynaptic plasma membrane. When presynaptic plasma membranes are blotted to nitrocellulose sheet, either¹²⁵I-botulinum neurotoxin or botulinum toxin-gold complexes bind to a M_r 140,000 protein. Botulinum toxin-gold complexes have also been used to study the toxin internalization process into Torpedo synaptosomes. The images fit the three step sequence model in the pathway of botulinum neurotoxin poisoning.     

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.     

In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension

Changes in tissue protein synthesis in hypertension have usually been measured in vitro in heart from acutely hypertensive rats without consideration of changes in atrial or pulmonary tissue or changes occurring in long-standing hypertension. The objective of the study was to investigate the in vivo changes in cardiopulmonary protein synthesis in three different rat models of chronic hypertension. Hypertension in aortic constriction, the Goldblatt model, and the bromoethylamine model were induced in rats for 30 days. At the end of the experimental period, in vivo rates of protein synthesis were measured with a flooding dose of [3H]phenylalanine (a method which effectively considers precursor pools). Concomitant measurements included quantification of contractile protein and RNA and DNA contents. Indices of protein breakdown were also assessed by selective measurement of protease activities. At the end of 30 days, aortic constriction induced marked increases in protein contents of the left ventricle, septum, left atria, and lungs. Accompanying changes included concomitant increases in RNA and DNA contents. Left ventricular myofibrillary, sarcoplasmic, and stromal protein contents increased in the aortic constriction model. Less marked changes occurred in the Goldblatt model, though the left atria were not significantly affected. In contrast, the bromoethylamine model had no effect on the protein or RNA contents of any region. In all cardiac regions of all three models, fractional rates of protein synthesis were not significantly affected. However, protein synthesis increased in the lungs of both the Goldblatt and bromoethylamine models at 30 days. Protease activities were decreased in the left ventricles of all three models at 30 days, with lysosomal protease activities declining in the aortic constriction model and cytoplasmic protease activities declining in the other two models. The failure of chronic hypertension to increase ventricular synthesis rates may represent inherent limitations in the time frame for measuring protein synthesis in vivo. However, at earlier time points (i.e., 10 days), the aortic constriction model was characterized by marked increases in left ventricular and atrial protein contents, RNA contents, and fractional rates of protein synthesis. This was consistent with the supposition that, in acute phases of hypertrophy, rates of protein synthesis increase, whereas in established hypertrophy, synthesis rates remain unchanged or decrease. The applicability of the aortic constriction model was investigated by examining the effects of the angiotensin converting enzyme inhibitor lisinopril (5 mg/kg/day). After 30 days treatment, lisinopril impeded the increase in left ventricular mixed and myofibrillar proteins. This effect was accompanied by an apparent increase in protein synthesis. In conclusion, although all three chronic models are able to induce hypertension, varying degrees of hypertrophy develop, which are more pronounced in the aortic constriction model. Accompanying changes include hypertrophy in the atria, reduced rates of ventricular proteolytic activity, and altered rates of protein metabolism in the lungs.     

Regulation of skeletal muscle development by the central nervous system in the fetal pig

The effect of upper motor neuron regulation on skeletal muscle development was studied in the fetal pig. A region of the spinal cord at the level of the upper cervical vertebrae was destroyed by cauterization at 45 days of gestation in four pig fetuses. Five fetuses with intact spinal cords served as controls. Innervation and enzyme activities in the longissimus muscle, the ultrastructure and quantitation of satellite cells in the sartorius muscle, and plasma composition were evaluated at 110 days of gestation. The terminal innervation ratios were similar (P greater than 0.05) for muscles from control and cauterized fetuses. Endplate morphology was also similar. Therefore, innervation of newly formed primary fibers is not controlled by upper motor neurons after 45 days of gestation. Mean values for body weight, percentage of muscle dry weight, percentage of myofibers with myonuclei and plasma levels of protein, glucose, triglycerides, lactate, and creatine phosphokinase activity were similar (P greater than 0.05) between the two groups of fetuses. All but one muscle fiber examined was of the secondary fiber type. These observations suggest that the physiological maturity of the muscle was not appreciably altered even though glucose-6-phosphate dehydrogenase activity was higher (P greater than 0.05) and total phosphorylase activity was lower (P greater than 0.05) in the spinal cauterized fetuses than in the control group. The percentage of satellite cells was lower when based on the number of myofibers observed (P greater than 0.005) or on the number of nuclei contained within the basal lamina (P greater than 0.001) in the muscle of the spinal cauterized fetuses than in the control fetuses. The cytoplasm of satellite cells from the muscles of control fetuses was rich in organelles indicative of metabolic and mitotic activity whereas a paucity of such organelles was observed in the satellite cells of cauterized fetuses. Since the percentage of myofibers that had myonuclei was similar (P greater than 0.05) for the control and cauterized fetuses, it appeared that the myonuclear population was maintained by direct incorporation of the parent satellite cell.     

Limitations of the electrocardiographic response to exercise in predicting coronary-artery disease.

The electrocardiographic response to exercise was compared with the results of coronary angiography in 89 patients with Type II hyperlipoproteinemia who had previous myocardial infarction or typical angina or both (43 patients)(Group A), "atypical angina" (16 patients)(Group B)or positive electrocardiographic response to exercise without other evidence of cardiac disease (30 patients)(Group C). Thirty-nine of 43 in Group A had greater than or equal to 50 per cent stenosis, and 26 (67%) of these 39 had negative exercise tests. In Group B, five of the 16 had greater than or equal to 50% stenosis, and three had positive exercise tests (one patient had a false-positive test). In Group C, eleven of 30(37%) had greater than or equal to 50% stenosis; however, nine (30%) had minor stenosis (less than or equal to 50%), and 10(33%) normal coronary arteries. The diagnostic usefulness of exercise electrocardiography is limited. False-negative responses are frequent in patients with clinically suspected coronary disease, and false-positive responses frequent in asymptomatic patients.