Onset of peak impairment after diazepam and after alcohol.

Single doses of diazepam induced peak impairment of performance on cognitive and psychomotor tasks early (20 min after ingestion), when blood levels had reached less than two thirds of their eventual plateau. Alcohol did not have this effect. Early peak impairment and the acute tolerance that follows it contribute greatly to the lack of correlation between diazepam plasma level and performance impairment.

Effects of oral contraceptives on diazepam-induced psychomotor impairment.

Eight young women taking oral contraceptives and 10 young men each received three different doses of diazepam, 0.07, 0.14, and 0.28 mg/kg. The women also received each dose both on days 10 and 28 of an oral contraceptive cycle. Performance based on both a psychomotor and cognitive-encoding task was significantly impaired after a 0.28-mg/kg dose of diazepam in women taking oral contraceptives and in men. In general, however, impairment in performance was less on day 10 than on day 28 of the oral contraceptive cycle. The onset of behavioral impairment was also slower on cycle day 10 than on day 28; peak impairment was reached at 20 min after dosing for men and women on day 28, but at 60 min for women on day 10. The cycle phase effects are potentially dangerous because of their unexpected nature. Individuals may obtain an expectation of intoxication based on the 21-day OC period yet experience capriciously greater acute impairment during their 7-day menstrual pause.

Profile of acute tolerance to three sedative anxiolytics.

Acute tolerance, defined as a decreasing drug effect relative to drug-plasma levels (DPL) over a period of minutes to a few hours, is pronounced following single doses of diazepam or pentobarbital. Both of these lipid-soluble drugs produce an early peak behavioral impairment and subsequent rapid recovery component that is followed by a much slower blood-drug rise time. These pronounced early peak effects were not shared by alcohol, and contribute significantly to the lack of correlation between impairment and DPL.

Use of simple tasks to test for impairment of complex skills by a sedative.

Examination of the effect of three doses of pentobarbital on the comparative performance of a complex psychomotor task with two simple neuromotor tasks, i. e., standing steady and pendulum eye tracking, revealed a high correlation. These simple tasks could be used as measures of intoxication since they do not require extensive training. Examination of the complex task impairment blood level ratio revealed that impairment relative to blood level was much greater in the absorption phase. This changing ratio underscores the point that blood levels alone are not an adequate estimate of intoxication.

Thin malignant melanomas of the head and neck.

Historically, Breslow classified thin melanomas as invasive lesions less than 0.76 mm in depth with rare instances of recurrence and mortality. From 1970 to 1990, 87 patients with thin head and neck melanoma were treated at Duke Medical Center. A computer-aided retrospective analysis was performed. Recurrence occurred in 30% of these patients; however, of the 66 patients seen at this institution prior to recurrence, only 8% recurred. Recurrence significantly shortened survival. Compared to an overall 84% 5-year survival, there was less than a 50% 5-year survival after recurrence. For thin melanomas, thickness did not affect survival. There was no difference in survival between thin melanomas and those ranging from 0.76 to 1.5 mm. A multivariate analysis was performed. The data suggest that thin melanomas of the head and neck may recur at a higher rate than previously reported and in addition, that they can be lethal.

Lentigo maligna melanoma of the head and neck.

Historically, lentigo maligna melanoma has been considered a "favorable" histological type of melanoma, and treatment by wide local excision was considered curative. A retrospective multivariate analysis of 143 head and neck patients with stage I lentigo maligna melanoma was performed from a database of 1067 head and neck patients followed at Duke Medical Center. Fifty-six percent of all lentigo maligna melanomas presented with lesions deeper than 0.76 mm, and 8% presented with stage II or III disease. Recurrent disease occurred in 45% of stage I patients, with a 5-year disease-free interval of 6 years and a median survival time of 10 years. Multivariate analysis demonstrated no significant difference in disease-free interval or survival by histological subtype. The data suggest that treatment should be based on tumor thickness and not histologic subtype.

An assessment of spectral analysis of amphetamine-induced behavior.

Testing of a new radio frequency capacitance field type transducer and power spectrum analysis system for assessment of rat behavior is described. Power spectrum estimates of amphetamine-induced behavior had an orderly relationship with behavior ratings ranging from inactive to intense stereotypy. The effects of thorazine dose-response blocking on amphetamine-induced behavior were linear. Separation between adjacent doses could not be accomplished with a single frequency, but required differential frequency-time period information.

Four digital algorithms for activation detection from unipolar epicardial electrograms.

The reproducibility of activation detection by each of four algorithms used to calculate maximum derivatives was tested on two sequential paced beats of right ventricular unipolar epicardial electrograms which represented either local activation of the right ventricle alone or synchronous activation of both ventricles. The methods were evaluated by comparing the shape of the two beats aligned on their selected activation times, i.e., the time at which the maximum negative deflection occurred, the differences in activation intervals for the two beats, and the effect on the activation time of superimposing distant events on local activation. The 17-point second-order data fit algorithm performed slightly better than the first-order difference, three-point Lagrange derivative, and five-point second-order data fit algorithms except that activation time selection by the 17-point technique was slightly, but significantly, delayed by the superposition of distant potentials. The 17-point second-order data fit technique is therefore recommended for use in detecting activation unless computation time is a major consideration. In that case, the five-point second-order data fit technique, which uses only four data values for each computation, can be used with only slight decreases in accuracy.

Cochlear implantation in the congenitally malformed ear.

A child with a congenital hearing loss and auricular malformations was evaluated for cochlear implantation. Preoperative radiologic studies demonstrated a common cavity cochlear malformation and a contralateral narrow internal auditory canal. Intraoperative findings included an aberrantly coursing facial nerve, preventing routine placement of the electrode array. The surgical approach was consequently modified and the cochlea was accessed through a malformed semicircular canal. Cochlear implantation can be performed safely and effectively in children with congenitally malformed ears.

Hearing preservation using the modified translabyrinthine approach.

Removal of an acoustic neuroma using the translabyrinthine approach has previously been considered "incompatible" with hearing preservation. By modifying the approach and preventing the loss of endolymph, we have successfully removed two intracanalicular acoustic neuromas that originated from the inferior vestibular nerves, and preserved serviceable hearing in the ears operated on. This report represents the preliminary findings using this particular technique in the management of intracanalicular acoustic neuromas.

Multidisciplinary management of Hunter syndrome.

Hunter syndrome is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In the absence of sufficient enzyme activity, glycosaminoglycans accumulate in the lysosomes of many tissues and organs and contribute to the multisystem, progressive pathologies seen in Hunter syndrome. The nervous, cardiovascular, respiratory, and musculoskeletal systems can be involved in individuals with Hunter syndrome. Although the management of some clinical problems associated with the disease may seem routine, the management is typically complex and requires the physician to be aware of the special issues surrounding the patient with Hunter syndrome, and a multidisciplinary approach should be taken. Subspecialties such as otorhinolaryngology, neurosurgery, orthopedics, cardiology, anesthesiology, pulmonology, and neurodevelopment will all have a role in management, as will specialty areas such as physiotherapy, audiology, and others. The important management topics are discussed in this review, and the use of enzyme-replacement therapy with recombinant human iduronate-2-sulfatase as a specific treatment for Hunter syndrome is presented.

Management of tracheal stenosis in children.

OBJECTIVE: Review presentation and outcome in pediatric patients identified either because of complete tracheal ring malformation or those undergoing tracheal resection or partial cricoid resection with primary tracheal anastomosis. DESIGN: Retrospective chart analysis in an academic tertiary referral pediatric hospital in the United States. PARTICIPANTS: Twenty-three children undergoing surgical repair of complete tracheal ring malformation from 1985 to 1995. Sixteen children with tracheal stenosis undergoing resection from 1984 to 1995. RESULTS: In patients with complete tracheal rings the mortality rate is 39% (9/23) with 47% (11/23) now extubated. The recent mortality rate is 25% (2/8) with 62% (5/8) now extubated. Sixteen patients underwent tracheal resection or cricotracheal resection. Twelve patients had tracheal resection with primary tracheal anastomosis. Eleven of these are now decannulated (92%). Four patients underwent partial cricoid resection with primary thyrotracheal anastomosis. All of these patients are decannulated without need for further surgery (100%).

Cochlear implant-related osteoneogenesis in an animal model: fluorescent labeling.

Cochlear osteoneogenesis may result from a variety of pathologic conditions, including cochlear implantation. The etiology of cochlear osteoneogenesis following implantation, however, is not known. Cochlear implant-related osteoneogenesis has been demonstrated in laboratory animals, but the specific cause, extent, or time-course of this process has not been determined. In this preliminary study, fluorescent bone labels were used to assess osteoneogenesis in six chinchillas in three experimental categories: surgical trauma to the cochlea, chronic nonstimulated cochlear implantation, and intrascalar neomycin infusion. Computer image analysis was used to measure the area of labeled bone on representative mid-modiolar histologic sections. The amount of bone deposition was greatest in ears treated with intracochlear neomycin (mean = 2.3835 mm2, SD = 3.7308). Surgical trauma alone (mean = 0.9549 mm2, SD = 1.384) and chronic implantation without stimulation did not produce substantial bone growth when compared to contralateral control ears (mean = 0.0574 mm2, SD = 0.0731). Fluorochrome labeling was also used to differentiate types of bone deposition. The morphology and timing of new bone growth appeared to be related to the type of cochlear injury. These results confirm that intracochlear neomycin may contribute to osteoneogenesis in animal studies of cochlear implantation. This study supports the use of fluorescent bone labeling in the evaluation of cochlear osteoneogenesis.