An evaluation of various methods of treatment for Legg-Calvé-Perthes disease.

An analysis of 5 methods of treatment for Legg-Calvé-Perthes disease was done on 124 patients with 141 affected hips. Before treatment, all groups were statistically similar concerning initial Mose measurement, age at onset of the disease, gender, and Catterall class. Treatments included the Scottish Rite orthosis (41 hips), nonweight bearing and exercises (41 hips), Petrie cast (29 hips), femoral varus osteotomy (15 hips), or Salter osteotomy (15 hips). Hips treated by the Scottish Rite orthosis had a significantly worse Mose measurement across time interaction (repeated measures analysis of variance, post hoc analyses, p < 0.05). For the other 4 treatment methods, there was no statistically different change. At followup, the Mose measurements for hips treated with the Scottish Rite orthosis were significantly worse than those for hips treated by nonweight bearing and exercises, Petrie cast, varus osteotomy, or Salter osteotomy (repeated measures analysis of variance, post hoc analyses, p < 0.05). There was, however, no significant difference in the distribution of hips according to the Stulberg et al classification at the last followup.

Characterization of mianserin neuroprotection in experimental spinal trauma: dose/route response and late treatment.

The neuroprotective action of the 5-hydroxytryptamine (5-HT2/5-HT1C) antagonist mianserin was examined with respect to optimal dosage, route of administration and time of treatment after a moderate spinal impact trauma (50 g.cm by the weight-drop method) to the thoracic region of the rat. In a previous study (Salzman et al., 1991b) a single 1-mg/kg i.v. dose of mianserin improved multiple measures of functional outcome when given 15 min after injury, whereas higher doses (5 and 10 mg/kg i.v.) displayed lesser therapeutic actions as well as pulmonary depressant effects. In these studies, lower dosages of minanserin (0.5 and 0.1 mg/kg i.v.) also were not associated with neuroprotection. Although the 1-mg/kg i.v. dosage again displayed significant efficacy when administered at 15 min delaying treatment to 30 min resulted in only marginal therapeutic actions. Nonetheless, i.p. dosage of 10 mg/kg (but not 2.5 mg/kg) at 15 min retained therapeutic efficacy, suggesting a pharmacodynamic influence. In support of this conclusion, the intrathecal administration of a 50-fold lower dose of minanserin (0.006 mg) at 15 min after injury resulted in neuroprotection that was superior to that of peripheral doses and was retained when this intrathecal dosage was administered at 1 hr after trauma. These results suggest a central mechanism of action for mianserin. Consistent with this was the lack of effect of mianserin (1 mg/kg i.v. at 15 min) upon post-traumatic spinal edema but its ability to reverse the decrease in central 5-HT oxidative metabolism after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma.

The ability of the serotonin antagonist mianserin to improve neurological recovery after graded impact trauma to the thoracic region of the spinal cord was compared to that of cyproheptadine and ketanserin in pentobarbital-anesthetized rats. Spinal cord injury was produced at T-10 by the weight-drop method and confirmed by the disappearance of the somatosensory-evoked response during the subsequent 15 minutes. In all experiments, drug or vehicle treatments were randomly administered as a single intravenous bolus 15 minutes after injury. Functional outcome was blindly assessed for 2 weeks after injury using a modified Tarlov scale, and in some cases, the Rivlin-Tator angleboard test. The survival of descending raphe-spinal axons was determined by the measurement of serotonin in postmortem spinal tissues located above and below the site of injury. In separate acute experiments, the physiological and hemodynamic correlates of a 50 gm cm injury and either mianserin or vehicle injection were examined, as were the effects on serotonin content and metabolism in spinal tissues harvested 30 minutes after injury. All doses of mianserin were associated with some index of improved recovery following a 50 gm cm injury, with a 1-mg/kg dose being clearly superior. Both ketanserin (0.1 mg/kg) and cyproheptadine (2 mg/kg) displayed marginal therapeutic actions for 50 gm cm injuries. In acute studies, mianserin at 1 mg/kg was associated with the preservation of posttraumatic spinal cord blood flow at T-12 as well as a pronounced alteration in postmortem spinal serotonin content and metabolism, in contrast to vehicle control treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of a serotonin antagonist, opioid antagonist, and TRH analog for the acute treatment of experimental spinal trauma.

The therapeutic efficacies of a serotonin antagonist (mianserin), an opioid antagonist (nalmefene), and a TRH analog (YM-14673) were compared in a well-characterized model of experimental spinal trauma in the rat. Injury was produced by the weight-drop method at T10 and confirmed by the disappearance of the somatosensory evoked response during the subsequent 15 minutes. Drug or vehicle treatments were administered randomly as a single intravenous bolus 15 minutes after injury. Functional outcome was blindly assessed for 2 weeks postinjury using a modified Tarlov scale and the Rivlin-Tator angleboard test. The survival of descending raphe-spinal axons was determined by measurement of serotonin in postmortem spinal tissues located above and below the injury, and histopathologic studies were carried out at the site of injury. All agents displayed similar and significant efficacies with respect to Tarlov and Rivlin-Tator measures of motor recovery and preservation of raphe-spinal fibers below the lesion site. In contrast, none of the agents were effective for preserving the central gray matter or myelin staining in the white matter in slices of tissue from the site of injury. Results are discussed in terms of the early treatment of spinal cord injury and future clinical trials.