A new sustained release dosage form of valproic acid (VPA) was developed. The new sustained release dosage form was administered (twice, with and without food) to five dogs in comparison to a standard tablet (Depakine, Labaz) and an i.v. preparation of the drug. Drug level monitoring in the plasma was performed by a GLC assay. Results indicate that the sustained release formulation exhibited a more prolonged and uniform absorption rate, yielded more sustained plasma levels after ingestion, and showed an overall bioavailability of 0.84 (95 per cent C.I. = 0.72, 0.96) relative to an equivalent dose of a conventional tablet.

Animals↗

PubMedDate not supplied

Pharmacokinetic evaluation of novel sustained-release dosage forms of valproic acid in humans.

Five new sustained-release dosage forms of valproic acid (VPA) were developed. The new sustained-release formulations were administered to six healthy subjects for comparison with a standard tablet and an i.v. preparation of the drug. Three of the formulations exhibited a more prolonged and uniform absorption rate and yielded more sustained serum levels after ingestion. These three formulations maintained serum therapeutic levels of VPA for 24 h after a single oral administration of 1 g, and were bioequivalent to a marketed standard tablet of VPA. The absorption profile of the various oral formulations was analysed pharmacokinetically, using the Loo-Riegelman procedure.

Administration, Oral↗

PubMedDate not supplied

Relation between absorption half-life values of four novel sustained-release dosage forms of valproic acid in dogs and humans.

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Administration, Oral↗

PubMedDate not supplied

Pharmacokinetic analysis of sustained-release dosage forms of theophylline in humans: comparison of single and multiple dose studies.

A pharmacokinetic analysis of two sustained-release dosage forms of theophylline (Theo-Dur and Theotrim) was carried out following single and multiple dose administrations of the two formulations in five healthy subjects. Despite the prolonged absorption after administration of the two sustained-release formulations, theoretical predictions of theophylline steady-state levels following multiple dosages based upon data obtained from the single dose study, correlated with the data of the multiple dose study. This study shows that the recommended dose and dosage regimen of new sustained-release formulations of theophylline can be based upon single dose studies. In the population studied, repetitive doses of 450 mg b.i.d. of Theo-Dur and Theotrim maintain steady-state concentrations of theophylline within the drug's therapeutic window.

Absorption↗

PubMedDate not supplied

Composite mucochondral flap for repair of cerebrospinal fluid leaks.

BACKGROUND: Cerebrospinal fluid leaks from defects in the anterior cranial fossa present a difficult management problem. Particularly when the defects are large, conventional techniques may not be sufficient to close them. We describe a new technique for treating such CSF leaks using a composite mucochondral flap from the nasal septum. METHODS: We treated five patients with the composite mucochondral flap. All patients were women aged 29-60 years. Two patients had an encephalocele, one had an esthesioneuroblastoma, and one had adenocarcinoma; one leak was spontaneous. RESULTS: The CSF leak was successfully closed in all five patients. No patients have experienced recurrence; the longest follow-up has been 39 months. The donor site on the septum healed without complication in all patients. CONCLUSIONS: The composite flap is useful for repairing large defects or after radiotherapy or trauma. The advantage of skeletal support to counter the pressure exerted by CSF seems clear.

Adult↗

PubMedDate not supplied

Reconstruction of the subglottic larynx with a myoperiosteal flap: clinical and experimental study.

The literature describes numerous techniques for reconstruction of the subglottic larynx. The use of rigid bone grafts or flaps has been associated with problems because the rigid bone cannot conform to the defect and form an airtight seal. We have performed subglottic reconstruction using the sternocleidomastoid myoperiosteal flap with very optimistic results on long-term follow up. The sternocleidomastoid myoperiosteal flap is a relatively simple procedure that can be used for a large variety of defects. The pliable periosteal flap used for closing the defect can be molded over a stent to form an airtight seal. We have demonstrated bone formation in the periosteum which is crucial to the stability of the airway and long-term success of the procedure. The sternocleidomastoid myoperiosteal flap yields a pliable, durable tissue capable of airtight closure and a tension-free suture line. This technique will make the closure of subglottic defects a much more practical task.

Aged↗

PubMedDate not supplied

Anterior glossectomy: reconstruction with a posterior tongue rotation flap.

With traditional techniques, reconstruction of the anterior tongue is often less than satisfactory. The difficulty lies mainly in providing the tongue with the appropriate amount of bulk essential for normal movement and function. We present an alternative method that involves raising a flap from the ipsilateral middle third of the tongue and rotating it into position for suturing to the anterior defect border. We have found this simple procedure to yield adequate tongue bulk for normal speech and deglutition.

Glossectomy↗

PubMedDate not supplied

Preoperative evaluation for partial laryngectomy.

The object of this study was to determine if pulmonary function tests were necessary in the preoperative evaluation of potential candidates for conservation laryngeal procedures. In addition, pulmonary complications from a series of partial laryngectomies were examined and correlated with a previous history of chronic obstructive lung disease. Ninety-four patients with laryngeal tumors amenable to a partial procedure were assessed preoperatively by testing their pulmonary function by stair-climbing; they were considered to possess enough pulmonary function to permit a partial procedure. Pulmonary function tests were obtained in 69 of these patients. Measurements of vital capacity and forced expiratory volume in 1-second were reviewed and correlated with the postoperative development of pulmonary complications to determine if these tests of pulmonary function could reliably predict which patients would be more prone to developing pulmonary complications. The results indicated that pulmonary function tests or a prior history of chronic obstructive pulmonary disease (COPD) could not reliably predict postoperative complications.

Adult↗

PubMedDate not supplied

Myosin changes in experimental 2,4-dichlorophenoxyacetate myopathy.

Young rats treated with 10 to 14 daily injections of 2,4-dichlorophenoxyacetate (2,4-D) developed a myopathy mainly involving fast muscles. Myosin isolated from the gastrocnemius muscles of treated and normal control animals differed in several respects. The Ca2+- and Mg2+-mediated ATPases were higher in myopathic muscle myosin than in normals. Alkylation of thiols by N-ethylmaleimide (NEM) induced an increase of Ca2+-activated ATPase that was higher in normal than in myopathic myosin. Trinitrophenylation of reactive amino groups by 2,4,6-trinitrobenzene sulfonate (TBS) induced on increase in Mg2+-mediated ATPase in both preparations, but the increase was higher in normals. Although the heavy- and light-chain pattern was identical in normal and myopathic myosin, during storage at 0 degrees C the relative amount of myopathic L2 light chain decreased. Myosins fragmented either by limited proteolysis with trypsin and chymotrypsin or by specific cleavage at tryptophanyl and cysteinyl peptide bonds showed differences on sodium dodecylsulfate (SDS)-polyacrylamide-gel electrophoresis. The results indicate that there is a change in the heavy chains of myosin isolated from the gastrocnemius muscle in 2,4-D-induced rat myopathy.

2,4-Dichlorophenoxyacetic Acid↗

PubMedDate not supplied

Elements in muscle measured in vivo and in vitro with X-ray spectrometry.

Calcium, iron, copper, and zinc concentrations in muscle were measured in vivo by x-ray spectrometry (XRS). The undersurface of the tongue was examined in cardiomyopathic and in normal hamsters. Values were compared to in-vitro analyses of various muscles from the same groups of animals using XRS and chemical analysis. Blood tests as well as histologic and histometric examinations were also performed. The correlated results show that XRS is a relatively sensitive and practical method for measuring chemical elements in muscle, and that it could be developed into a useful clinical test in certain neuromuscular and myocardial diseases. An interesting incidental finding was that, though all the examined muscles of myopathic animals had pathologic changes, only the tongue and myocardium, which are composed exclusively of red fibers, showed excessive calcium accumulation. This suggests either that the basic genetic aberration is not directly related to the oxidative metabolism, or that white muscles have a more efficient system for dealing with calcium overload.

Animals↗

PubMedDate not supplied

Modern methodologies of differentiating thyroid masses.

The rational treatment of thyroid diseases requires an understanding of the thyroid function and an accurate evaluation of its functional (endocrine), as well as it morphological alteration. There are several different imaging techniques which are available and are in use in the evaluation of thyroid diseases. In this article we present a protocol for the use of diagnostic imaging to evaluate a focal thyroid mass, a diffusely enlarged gland, regional, and distant metastatic disease. The current diagnostic applications of radionuclide scanning, ultrasound, computed tomography, and magnetic resonance imaging (MRI) will be discussed.

Diagnostic Imaging↗

PubMedDate not supplied

Surgical treatment of rectal carcinoma: results of anterior resection vs. abdominoperineal resection at a community hospital.

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Adenocarcinoma↗

PubMedDate not supplied

Nonlinear feedback models for the tuning of auditory nerve fibers.

The tuning of auditory nerve (AN) fibers is generally characterized by an increase in bandwidth and, for mid- to high-frequency fibers, a downward shift in the center frequency as sound level increases. Changes in bandwidth are accompanied by changes in the phase properties of the fibers; thus the timing of neural discharges also changes as a function of sound level. This study focuses on the magnitude and phase properties of models designed to reproduce the nonlinear properties of AN fibers that were studied electrophysiologically. The forward path of each model consisted of a linear second-order resonance, and each feedback path contained a saturating nonlinearity. In model 1, the feedback path was a simple memoryless, saturating nonlinearity. In model 2, a low-pass filter was added after the feedback nonlinearity. The ability of each model to simulate aspects of the nonlinear tuning of AN fibers is discussed. Model 2 was able to simulate a wider range of nonlinear behavior for different AN fibers and thus has promise for use in simulations of populations of fibers tuned to different frequencies.

Animals↗