Pharmacokinetics of intravenous bepridil in patients with coronary disease

The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing.     

Interactions of small polypeptides with dimyristoylphosphatidylcholine monolayers: effect of size and hydrophobicity

The effects of size and hydrophobicity of small (molecular weights below 2,000) polypeptides on their predominantly hydrophobic interactions with a neutral phospholipid monolayer were studied. The changes in surface pressure were determined when various concentrations of Gly, Gly-Gly-Gly, -Ala, -Ala- -Ala- -Ala, -Ala-Gly-Gly-Gly-Gly, -Phe- -Leu- -Glu- -Glu- -Leu, adrenocorticotropic hormone fragments 1–10 (ACTH-(1–10)), porcine β-lipotropin, -endorphin and human fibrinopeptide A were injected under dimyristoylphosphatidylcholine (DMPC) monolayers at an initial surface pressure of 10 dyne/cm. In all cases, when peptides with the same number of residues are compared, the concentration needed to increase the surface pressure of the film by 1 dyne/cm was inversely related to its hydrophobicity. A reasonably good correlation was found to exist between the calculated free energy of transfer of a polypeptide from ethanol to water (a measure of its hydrophobicity) and its ability to increase the surface pressure of the DMPC film (a measure of the extent of its interaction with the neutral lipid monolayer).     

Use of pins and plaster in the treatment of unstable pediatric forearm fractures

The treatment of unstable forearm fractures in children remains a challenging and controversial subject. There are times when more rigid fixation is needed to obtain and maintain fracture reduction. Open reduction/internal fixation or intramedullary nailing can be avoided by the use of the technique of pins and plaster. This study reviewed 20 forearm fractures treated between 1978 and 1984. All fractures healed uneventfully in satisfactory alignment. No complications were encountered. We conclude that the method of pins and plaster is a safe and reliable method to treat unstable pediatric forearm fractures.     

Retrospective multicenter analysis of 3i endosseous dental implants placed over a five‐year period

Osseointegrated dental implants have now become an accepted form of treatment for patients with a fully or partially missing dentition. The purpose of this study was to evaluate the performance of 3i threaded and cylindrical implants. During a 5-year period, a total of 1969 3i endosseous implants were placed at 6 centers in the United States and 2 elsewhere in the edentulous and partially edentulous jaws of 653 consecutive patients ranging in age from 18 to 82 years. Of the total number of implants placed, 1341 were commercially pure titanium threaded implants and 628 were titanium plasma-sprayed implants with a cylindrical configuration. A total of 28 patients with 110 implants were lost to follow-up. Implants in these patients were considered neither a success nor a failure. Success was predicated on the osseointegration of each and every implant followed in this analysis rather than the persistence of prosthetic function. Confirmed bone anchorage was considered essential for success. A total of 625 patients with 1871 implants remain in the study with a follow-up period ranging from 6 to 60 months. A total of 93 implants (5.0% of the total implants followed) were considered as failures. A mean implant survival rate was 95.0% for both the threaded and the cylindrical implant was calculated. The success rate of threaded implants was 97.0% in the mandible and 93.8% in the maxilla. The success rate for the 3.3mm cylindrical implants was 96.0% in the mandible and 95.5% in the maxilla, and the success rate of 4.0mm diameter cylindrical implants was 95% in the mandible and 92.0% in the maxilla. Causes of failure consisted of loss of osseointegration 2.3%crestal bone loss requiring periodontal therapy after the first year of function 1.7% and mechanical problems associated with the prosthesis 0.9%. This retrospective analysis of the 3i endosseous implant system is comparable to previous reports on other implant systems in terms of implant survival and prosthesis stability. It is demonstrated that 3i implants are predictable and can provide lasting osseointegration leading to improvement of oral function if the recommended surgical and restorative protocol is followed.     

Evidence of an abnormal intramuscular component of fatigue in multiple sclerosis

The goals of this study were to investigate muscle fatigue in patients with multiple sclerosis (MS), and to determine the relationships between muscle fatigue, clinical status, and perceived fatigue. The fatigability of the anterior tibial muscle was quantitated in patients and controls during 9 min of intermittent stimulation (used to eliminate central sources of muscle fatigue). During exercise, the decline in tetanic force, phosphocreatine, and intracellular pH was greater in patients than in controls. The compound muscle action potential amplitude did not decrease during exercise, indicating that there was no failure of neuromuscular transmission during fatigue. Thus, the excessive fatigue in MS developed from sources beyond the muscle membrane. Following exercise, the recovery of tetanic force was delayed in patients (a pattern that suggests abnormal excitation–contraction coupling), whereas the recovery of metabolites was complete in both groups. Muscular fatigue was correlated with clinical disability but not with perceived fatigue. These results suggests that fatigue in MS has both central (perception, upper motor neuron dysfunction) and peripheral (impaired metabolism and excitation–contraction coupling) components.© 1995 John Wiley &Sons, Inc.     

CONGENITAL DISLOCATION OF THE KNEE AS A CONSEQUENCE OF PERSISTENT AMNIOTIC FLUID LEAKAGE

SUMMARY A case congenital dislocation of both knees and dislocation of the left hip in an infant whose mother had a chronic amniotic fluid leakage after mid-trimester amniocentesis.     

Maternal and fetal plasma vitamin E to total lipid ratio and fetal RBC antioxidant function during gestational development

Placental transfer of vitamin E was investigated from 19 to 35 weeks of gestation by analysis of fetal and maternal blood samples for total tocopherol, total lipids, and fetal red blood cell antioxidant reserves. Fifty-two fetal blood samples were obtained under ultrasonographic guide by percutaneous umbilical blood sampling. Thirteen were from fetuses with gestational age less than or equal to 22 weeks (x serum vitamin E = 0.4 +/- 0.14 mg/dl), 12 were from fetuses at 23-27 weeks gestation (x serum vitamin E = 0.4 +/- 0.21 mg/dl), and 27 were from fetuses with gestational age 28-38 weeks (x serum level = 0.37 +/- 0.18). Total lipid levels ranged from 140 to 216 mg/dl. Maternal plasma vitamin E concentrations correlated significantly with concurrent values in the fetus. There were no significant differences in serum vitamin E levels or vitamin E to total lipid ratio in samples from early, mid, or late gestation in either the mother or fetus. Red blood cell antioxidant reserve on samples from 18 fetuses were grossly abnormal by three different functional assays. On the basis of these data, placental transfer of vitamin E appears to be relatively constant through advancing gestation. Red blood cell antioxidant reserve is uniformly low.     

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.