Effect of specimen fixation method on pullout tests of pedicle screws.

STUDY DESIGN: Experimental axial pullout tests of a new type of pedicle screw were done on cadaveric lumbar vertebrae. The manner in which specimens were secured in the testing apparatus was varied to determined influence of specimen fixation method on the maximum pedicle screw pullout force. OBJECTIVES: To determine the appropriateness of embedding (i.e., potting) spinal specimens in polymer resin (e.g., bone cement or Plastic Padding [Plastic Padding Ltd., High Wycombe, Buckinghamshire, England]) for axial pullout tests of pedicle screws. Several different specimen fixation methods were examined to make recommendations for the standardization of future experimental testing protocols. SUMMARY OF BACKGROUND DATA: Axial pullout of transpedicular screws, although not a likely clinical mode of failure, is a popular experimental testing mode for evaluating screw-bone biomechanics. A wide variety of techniques for securing a vertebral specimen to counter the axial pullout force has been reported (including the use of polymer resin) with a correspondingly wide range in the resulting axial pullout strengths. The possible influence of the specimen fixation method on pedicle screw axial pullout strength has not been addressed previously. METHODS: Axial pullout tests of pedicle screws (DDS, Plus Endoprothetik, Rotkreuz, Switzerland) from the pedicles of 21 isolated lumber vertebral bodies were done using a Model 810 MTS Universal Testing Machine (MTS Systems, Inc., Minneapolis, Minnesota). The specimens were secured in a custom-made vise fixture either as is or after the vertebral bodies were potted in Plastic Padding up to the pedicle origin. Some of the potted specimens were wrapped first in latex to prevent polymer resin intrusion, and the others were unprotected. Pullout tests were attempted on both the left and right pedicles of each specimen, and the maximum pedicle screw pullout force was recorded. Measurement of bone mineral density by means of dual energy x-ray absorptiometry, in addition to macroscopic and scanning electron microscopy histologic analyses, microradiography, and energy dispersive X-ray spectroscopy, was done post-test to assist in the interpretation of the data. RESULTS: The maximum pedicle screw pullout force was found to be dependent on both the bone mineral density and the mode of fixation of the vertebrae. Embedding in polymer resin without protection of the specimen (i.e., latex wrapping) led to several instances of well-documented polymer resin intrusion; in these specimens, mean maximum pedicle screw pullout force was significantly greater than that of specimens secured without polymer resin and that of embedded specimens for which intrusion did not occur. CONCLUSIONS: Polymer resin intrusion can have a significant effect on the biomechanical characteristics of the bone-pedicle screw interface. When polymer resins are used to secure vertebral specimens for in vitro biomechanical tests of the bone-pedicle screw interface, it is important to either prevent intrusion (e.g., with a latex wrapping) or document post-test (e.g., through the methods described in this article) that intrusion did not occur for the specimens included in the analysis.

Pharmacokinetics of intravenous cefmetazole with emphasis on comparison between predicted theoretical levels in tissue and actual skin window fluid levels.

Cefmetazole is a cephamycin antibiotic which is resistant to hydrolysis by various beta-lactamases. This study evaluated the pharmacokinetics of cefmetazole, including its intravascular and interstitial fluid distribution, by using the skin window (SW) technique. A 2-g dose of cefmetazole was given intravenously over 30 min to each of 12 healthy adult male volunteers every 6 h for nine doses. Plasma levels were assayed at predetermined intervals after doses 1, 5, and 9. Interstitial fluid levels were determined by the SW technique. Antibiotic levels were assayed by the agar well bioassay technique. A concentration-versus-time plot indicates that cefmetazole is rapidly distributed, with mean peak levels in plasma equal to 126 micrograms/ml at the end of the half-hour infusion. The mean plasma half-life was 1.1 h. Plasma and tissue distribution constants permitted calculation of theoretical levels in tissue. Parallel elimination slopes for SW and theoretical tissue level showed that the SW model distribution kinetics are closely related. The area under the curve for the SW was 73.9 mg.h/liter. This was comparable to the theoretical level in tissue, which was 96 mg.h/liter. Furthermore, the area under the curve of theoretical tissue level/plasma was 0.6 and that of SW/plasma was 0.47. These results demonstrate that the SW technique yielded a result quite close to the theoretical tissue level. Ultrafiltration analysis indicated that as cefmetazole levels in plasma increased from 10 to 250 micrograms/ml, plasma protein binding of the antibiotic dropped from 85 to 65%. Finally, 60 to 70% of the drug was recovered from the urine as biologically active drug over 6 h postinfusion.

Pharmacokinetics and metabolism of rimantadine hydrochloride in mice and dogs.

We studied the pharmacokinetics and metabolism of rimantadine hydrochloride (rimantadine) following single-dose oral and intravenous administration in mice and dogs. Absorption of the compound in mice was rapid. Maximum concentrations in plasma occurred at less than 0.5 h after oral administration, and the elimination half-life was 1.5 h. Peak concentrations in plasma following oral administration were markedly disproportional to the dose (274 ng/ml at 10 mg/kg, but 2,013 ng/ml at 40 mg/kg). The bioavailability after an oral dose of 40 mg/kg was 58.6%. Clearance was 4.3 liters/h per kg, and the volume of distribution was 7.6 liters/kg at 40 mg/kg. In contrast to the results observed in mice, absorption of the compound in dogs was slow. Maximum concentrations in plasma occurred at 1.7 h after oral administration, and the elimination half-life was 3.3 h. A further difference was that peak concentrations in plasma were approximately proportional to the dose. Following administration of a single oral dose of 5, 10, or 20 mg/kg, maximum concentrations in plasma were 275,800, and 1,950 ng/ml, respectively. The bioavailability after an oral dose of 5 mg/kg was 99.4%. The clearance was 3.7 liters/h per kg, and the volume of distribution was 13.8 liters/kg at 5 mg/kg. Mass balance studies in mice, using [methyl-14C]rimantadine, indicated that 98.7% of the administered dose could be recovered in 96 h. Less than 5% of the dose was recovered as the parent drug in dog urine within 48 h. Finally, gas chromatography-mass spectrometry studies, done with mouse plasma, identified the presence of two rimantadine metabolites. These appeared to be ring-substituted isomers of hydroxy-rimantadine.

Pharmacokinetics of a single dose of rimantadine in young adults and children.

Single doses of rimantadine were given to children and young adults to evaluate the safety and pharmacokinetics of this antiviral compound. The half-life of rimantadine in young adults was 27.7 +/- 4.9 h for tablets and 27.8 +/- 8.0 h for syrup preparations. A total of 10 children, 5 to 8 years old, received a syrup preparation of rimantadine. The half-life of rimantadine in children was 24.8 +/- 9.4 h. A single dose of rimantadine was well tolerated in young adults and children.

The successful marketing of a child and adolescent inpatient unit in a community hospital.

This article presents the development and implementation of a marketing plan designed for a 24-bed child and adolescent inpatient psychiatric unit in a 500+ bed community hospital. It includes questions raised while developing the marketing strategy and goals. Methods of implementation for specific target groups such as psychiatrists, pediatricians, school counselors, and clergy, are outlined. Assessment and consequent adjustments to the marketing plan based upon ongoing evaluation are discussed.

Comparative single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride in young and elderly adults.

The single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride were compared in a randomized, two-period, crossover study involving six young (less than or equal to 35 years) and six elderly (less than or equal to 60 years) adults. Subjects ingested single 200-mg oral doses after an overnight fast, and serial plasma (0 to 96 h), nasal mucus (0 to 8 h), and urine (0 to 24 h) samples were collected for assay of drug concentration by electron capture gas chromatography. For both groups combined, rimantadine differed significantly from amantadine in peak plasma concentration (mean +/- standard deviation, 0.25 +/- 0.06 versus 0.65 +/- 0.22 micrograms/ml), plasma elimination half-life (36.5 +/- 15 versus 16.7 +/- 7.7 h), and percentage of administered dose excreted unchanged in urine (0.6 +/- 0.8 versus 45.7 +/- 15.7%). No significant age-related differences were noted for rimantadine. Urinary excretion (0 to 24 h) of rimantadine and its hydroxylated metabolites averaged 19% of the administered dose. The maximum nasal mucus drug concentration was similar for both drugs (0.42 +/- 0.25 versus 0.45 +/- 0.32 micrograms/g), and the ratio of maximum nasal mucus to plasma concentration was over twofold higher after rimantadine than after amantadine. These findings may in part explain the clinical effectiveness of rimantadine in influenza A virus infections at dosages that have lower toxicity than those of amantadine.

Bioavailability of oral and intramuscular molindone hydrochloride in schizophrenic patients.

This study was designed to assess the bioequivalence of intramuscular molindone hydrochloride and marketed oral molindone. Ten schizophrenic patients (mean age, 30.2 years) received oral molindone in single daily doses of 100 or 150 mg for four to eight days followed by intramuscular molindone in single daily doses of 50 or 75 mg for four days. On the last day each molindone formulation was given, plasma samples were collected at baseline and at 0.5, 1, 2, 4, 6, 8, and 12 hours after administration. The pharmacokinetic measures of area under the curve and maximum concentration show that intramuscular molindone is 1.49 to 1.67 times more bioavailable than oral molindone. This finding indicates that once a patient's acute psychotic episode has been stabilized with intramuscular molindone, therapy can continue without interruption by substituting 1.5 mg of oral molindone for every 1 mg of intramuscular molindone. The time to maximum concentration occurred significantly earlier (P = 0.05) with intramuscular molindone (0.6 hours) than with oral molindone (1.1 hours). Elimination half-life values were approximately two hours for both formulations.

Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics.

In a double-blind, placebo-controlled study, the comparative toxicities and blood concentrations of amantadine hydrochloride and rimantadine hydrochloride were determined. Healthy, working adults ingested either 200 (n = 52) or 300 mg (n = 196) per day in divided doses for 4.5 days. Mean plasma drug concentrations at 4 h after the first dose were lower in rimantadine recipients given 100- (140 versus 300 ng/ml for rimantadine and amantadine, respectively; P less than 10(-5)) or 200-mg doses (310 versus 633 ng/ml; P less than 10(-5)). The plasma drug concentrations after the first dose correlated significantly with total symptom sources for both amantadine and rimantadine, but the plasma levels of toxic and nontoxic subjects overlapped extensively. At 300-mg/day dosage amantadine was associated more often with adverse central nervous system symptoms (33% of amantadine versus 9% of rimantadine recipients; P less than 0.001) and sleep disturbance (39 versus 13%; P less than 0.001), but not gastrointestinal symptoms (19.5 versus 16.0%). However, no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations. Amantadine and rimantadine differ in their pharmacokinetics but not in their potential for side effects at comparable plasma concentrations.

Progressive hearing impairment in children with congenital cytomegalovirus infection.

Audiological assessment of 86 children with congenital cytomegalovirus infection revealed progressive hearing loss in four of 12 subjects with sensorineural hearing impairments. Case descriptions are presented documenting the progression of the hearing loss. In view of the findings, children with congenital cytomegalovirus should be monitored closely to insure detection of possible delayed or progressive hearing impairment and delivery of appropriate habilitative services.