Prejunctional effects of muscarinic agonists on 3H-acetylcholine release in the rat urinary bladder strip

Summary The inhibitory effects of some muscarinic agonists on tritiated acetylcholine release evoked by field stimulation were investigated in the rat urinary bladder strip. The acetylcholine stores of the preparation were labelled with ³H-choline. Electrical field stimulation caused an outflow of tritium, reflecting the release of ³H-acetylcholine. The release of ³H-acetylcholine was decreased in a concentration-dependent manner by all the agonists tested: oxotremorine, muscarone, muscarine, carbachol and methylfurtrethonium. On the contrary, only muscarine and muscarone enhanced the basal efflux of tritium in a concentration-dependent fashion. Concentration-response curves were determined both at 2 Hz and at 1 Hz by using intermittent administration of the drugs. Maximal depression in release (by 78 – 82%) was observed in experiments at 1 Hz. A similar inhibition was obtained at 2 Hz frequency only when a low concentration of calcium (0.6 mM) in the medium was used. Oxotremorine was the most potent among the tested compounds with the same intrinsic activity as the other drugs. In contrast to the other agonists investigated, oxotremorine showed in about 10-fold greater potency at pre- than at postjunctional muscarine receptors in the rat urinary bladder. This difference might depend either on heterogeneity of muscarine receptors or on different mechanism(s) relating to the transducing properties of receptors at the pre- and postjunctional level. A comparison between the relative prejunctional potencies in the rat urinary bladder and in the guinea pig myenteric plexus (data from the literature) suggests that prejunctional muscarine receptors are similar in these tissues. Furthermore, the findings obtained with a low concentration of calcium in the medium may support the view that intraneuronal availability of calcium plays a significant role in modulating the prejunctional negative feed-back mechanism in the rat urinary bladder.Send offprint requests to Dr. G. D'Agostino at the above address     

QSAR in a series of muscarinic agents. Note VI. Five-membered cyclic ligands

Proceeding in our study on the muscarinic receptor site, a refinement of its topology by means of Quantitative Structure-Activity Relationships has been carried out. Specific key structures have been selected considering not only muscarine and the corresponding desether derivative, but also a set of cyclopentenyltrimethylammoniummethyl salts. These derivatives, considered in a correlation equation extended to all of the five-membered cyclic structures previously examined, significantly improve understanding of contributions of critical ligand substructures to the overall interaction. The results obtained reinforce the reliability of correlation equations in structure-activity studies.     

An anterior cruciate ligament (ACL) evaluation format for assessment of artificial or autologous anterior cruciate reconstruction results

The ACL evaluation format is a modification and extension of Marshall's approach to evaluation of ligamentous injuries of the knee, whereby functional and clinical improvement can be analyzed independently as well as cumulatively. There are three major parts entered on separate forms: history and surgery (Form 1); initial evaluation and follow-up (Form 2); and complications (Form 3). Form 1 has five sections: patient information (demography); history of injury; previous surgery; surgery performed; and postoperative course. Form 2 has six sections. These are the Lysholm knee function scoring scale, Tegner activity level rating scale, physical findings, complications, supplementary data, and Tegner activity level definitions. Form 2 records the preoperative and follow-up assessments for up to a five-year follow-up period. Form 2 can be used independently of the other forms. Form 3 elaborates in a detailed manner a complication occurrence. The format provides the evaluator with an easy to use, "computer/user friendly," method for the comprehensive assessment of artificial or autologous anterior cruciate reconstruction of the knee. The authors advocate the use of the ACL format as an international standard for data storage to facilitate comparison of results with accuracy and uniformity among investigation centers.     

Tendon-to-bone healing of a semitendinosus tendon autograft used for ACL reconstruction in a sheep model

Anterior cruciate ligament (ACL) reconstruction was performed in a single hind limb of 30 sheep using a doubled semitendinosus tendon graft. Three additional animals were used as controls. Histologic and biomechanical analysis was performed from 4-52 weeks postoperatively. Perpendicular collagen fibers were found connecting the tendon graft to the bone tunnels at 8 weeks. These fibers were seen circumferentially at 12 weeks. By 24 weeks, the bone tunnel was well-defined, and no further changes were observed at 52 weeks. Tendon incorporation within the femoral and tibial tunnels was similar at each interval. Although the small sample size did not permit statistical testing, the reconstruction strength was similar up to 12 weeks (15%-19% of controls). This increased at 24 (28%) and 52 (40%) weeks. The stiffness primarily increased from 4-8 weeks (18%-39%) and 24-52 weeks (52%-82%). Up to 12 weeks, failures occurred by graft pull-out from the bone tunnel. All 24- and 52-week specimens ruptured through the intra-articular portion of the graft, further indicating sufficient graft incorporation within the bone tunnels.     

Natural history of a hamstring tendon autograft used for anterior cruciate ligament reconstruction in a sheep model

The purpose of this study was to describe the histologic structure of the intraarticular segment of a semitendinosus tendon autograft used for anterior cruciate ligament reconstruction over the first year after surgery. We performed an anterior cruciate ligament reconstruction in a single hindlimb of 11 sheep using a doubled semitendinosus tendon autograft secured to the femur with an endoscopic button and polyester tape and to the tibia with sutures tied around a screw. The histologic structure of the intraarticular segment of the graft at 4, 8, 12, 24, and 52 weeks after surgery was compared with that of the normal semitendinosus tendon and anterior cruciate ligament. The random collagen fiber orientation progressed to a longitudinal orientation from the peripheral to the central areas of the graft over the initial 12 weeks after surgery. A uniform sinusoidal crimp pattern similar to that seen in the normal anterior cruciate ligament was identified under polarized light in nearly one-half of each graft by 24 weeks. Further maturation was noted at 52 weeks. Graft necrosis was not evident at any time period. This study showed that semitendinosus tendon autografts transform into a histologic structure similar to that of the normal anterior cruciate ligament over the initial year after surgery, as has been described for patellar tendon grafts.     

High School Injuries Basketball

Poor conditioning takes its toll in girls' high school basketball. An Oklahoma City girls' varsity team incurred over four times as many injuries per player as a boys' varsity team.     

Use of cholesterol-lowering therapy and related beliefs among middle-aged adults after myocardial infarction

OBJECTIVE: To assess use of cholesterol-lowering therapy and related beliefs among middle-aged adults after myocardial infarction. DESIGN: Telephone survey and administrative data. SETTING: National managed-care company. PARTICIPANTS: Six hundred ninety-six adults age 30 to 64 surveyed in 1999, approximately 1 to 2 years after a myocardial infarction. MEASUREMENTS: Use of cholesterol-lowering drugs, beliefs about the importance of lowering cholesterol, and knowledge of personal cholesterol level, adjusting for demographic and clinical factors with logistic regression. MAIN RESULTS: Among respondents, 62.5% reported they were taking a cholesterol-lowering drug. In adjusted analyses, these drugs were used significantly less often by African-American patients and those with congestive heart failure or peripheral vascular disease, and more often by college graduates, patients with hypertension, and those who had seen a cardiologist since their myocardial infarction. Lowering cholesterol was viewed as "very important"; by 87.1% of patients, but significantly less often by smokers and more often by those who had undergone coronary angioplasty or bypass surgery. Only 42.5% of respondents knew their cholesterol level, and this knowledge was significantly less common among less-educated or less-affluent patients, African-American patients, and patients who smoked or had diabetes or peripheral vascular disease. CONCLUSIONS: Although most patients recognized the importance of lowering cholesterol after myocardial infarction, several clinical and demographic subgroups were less likely to receive cholesterol-lowering therapy, and many patients were unaware of their cholesterol level. Health-care providers and managed-care plans can use these findings to promote cholesterol testing and treatment for patients with coronary heart disease who are most likely to benefit from these efforts.