Carbon dioxide laser repair of medial ectropion.

Five patients with medial eyelid ectropion and punctal eversion due to senile changes, cicatrix, or vertical skin tightness were treated with a heretofore unreported method. Using a carbon dioxide laser, an ellipse of conjunctival-tarsal-inferior muscle tissue was excised from the inner surface of the ectropic lid inferior to the punctum. There was no bleeding, and each postoperative course was notable for minimal pain and edema. Lengthy follow-up revealed good anatomic results, with normal functioning of the inferior punctum. Patients taking warfarin sodium (Coumadin) have been treated without bleeding. Carbon dioxide laser ectropion repair may be tailored to each patient's specific condition, and is performed with ease in the office, thus offering diminished patient anxiety, discomfort, and expense.

Amitriptyline normalizes tetrabenazine-induced changes in cerebral microcirculation.

The cerebromicrocirculation in the tetrabenzaine (TBZ) model of depression has been found to be abnormal with respect to (1) responsiveness of cerebral blood flow to increases in arterial CO2 content and (2) the effective permeability of the blood-brain barrier to water. Development of these abnormalities temporally paralleled the behavioral disturbances and catecholamine depletion induced by TBZ. These TBZ-induced changes occurred globally throughout the brain, being apparent in the forebrain, cerebellum, and medulla-pons. Pretreatment with the antidepressant amitriptyline prevented both behavioral and physiological effects of TBZ, whereas amitriptyline administered after TBZ was less effective. The results suggest that an important action of tricyclic antidepressants may be cerebromicrocirculatory effects.

Cerebromicrocirculatory defects in animal model of depression.

In the tetrabenazine (TBZ) model of depression, the cerebromicrocirculation was discovered to respond abnormally to metabolic demand as mimicked by the administration of CO2. Altered responsivity of cerebral blood flow and effective permeability of the blood--brain barrier to changes in PaCO2 were found. These physiologic defects coincided temporally with TBZ-induced depletion of central norepinephrine and dopamine and with the development of the behavioral effects of TBZ (the end points used to test the antidepressant potential of experimental drugs). Pretreatment with amitriptyline (a standard antidepressant and amine reuptake inhibitor) prevented the development of these TBZ-induced abnormalities in the cerebromicrocirculation, just as it prevented the behavioral effects.

A liquid chromatographic method for quantitating amitriptyline in brain tissue.

A previously reported method for measuring tricyclic antidepressants (TCA) in plasma was modified to measure TCA, specifically amitriptyline (AMI) and nortriptyline (NOR) in rat brain tissue. Brains obtained from drug-free and AMI-treated rats were extracted and assayed using a Waters high-performance liquid chromatograph. Drug-free brain tissue contained no substances which interfered with the assay of these TCAs. Drug recovery averaged 90 +/- 3.4% (mean +/- SEM). Seven intra-run assays of a spiked brain tissue sample yielded coefficients of variation of 2.7% for AMI and 1.8% for NOR. Seven inter-run assays of the same sample varied 4.2% for AMI and 3.5% for NOR. Five separate assays of a brain homogenate sample spiked with 50 ng/ml of drug yielded values of 50 +/- 2.1 SEM ng/ml for AMI and 54 +/- 1.1 SEM ng/ml for NOR. Standard curves were linear when constructed from samples in a concentration range of 250--3,000 ng/g wet weight tissue (r = 0.96, P less than 0.001).

Brain concentrations of tricyclic antidepressants: single-dose kinetics and relationship to plasma concentrations in chronically dosed rats.

A previously reported method of measuring tricyclic antidepressant concentrations in brain tissue and plasma was used to measure amitriptyline (AMI) in rats following drug administration using different routes, doses, and time intervals. In rats given AMI intraperitoneally (IP), brain concentrations increased during the first 30 min after drug administration and then declined. Brain concentrations increased linearly with changes in IP dosage and increased logarithmically with changes in intravenous dosage. No simple relationship existed between brain and plasma concentrations in acutely dosed rats. However, a linear relationship existed between plasma and brain concentrations in chronically treated animals (r = 0.96, P less than 0.001). The brain:plasma drug ratios observed in chronically treated rats corresponded to ratios reported in man. Thus, conclusions drawn from these studies can probably be extrapolated to the clinical situation. Based on our data, the molar concentration of drug achieved on therapeutic doses is 10(-5)--10(-6) M. This information may aid in understanding the clinical relevance of in vitro drug: receptor binding studies which are typically reported in molar concentrations.