Development and Mechanical Characterization of Bioadhesive Semi-Solid,Polymeric Systems Containing Tetracycline for the Treatment of Periodontal Diseases

Purpose. This study examined the mechanical characteristics and release of tetracycline from bioadhesive, semi-solid systems which were designed for the treatment of periodontal diseases. Methods. Tetracycline release into phosphate buffered saline (pH 6.8, 0.03 M) was examined using a Caleva 7ST dissolution apparatus at 37°C. The mechanical properties of each formulation (hardness, compressibility, adhesiveness, elasticity and cohesiveness) were determined using texture profile analysis. Syringeability was measured using the texture analyser in compression mode as the work of syringeability i.e. the force required to express the product from a periodontal syringe over a defined distance. Results. Tetracycline release from all formulations was zero-order for 24–54 h and ranged from 1.59 ± 0.20 to 15.80 ± 0.50 mg h^–1. Increased concentrations of hydroxyethylcellulose (HEC) decreased the rate of release of tetracycline, due to the concomitant increase in product viscosity and the subsequent decreased rate of penetration of dissolution fluid into the formulation. Conversely, an increased polyvinylpyrrolidone (PVP) concentration increased tetracycline release rates, due to an increased formulation porosity following dissolution of this polymer. Increased concentrations of HEC and PVP increased the hardness, compressibility and work of syringeability of the semi-solid formulations, due to increased product viscosity. An increase in formulation adhesiveness, a parameter related to bioadhesion, was observed as the concentrations of HEC and PVP were increased, illustrating the adhesive nature of these polymers. Increased concentrations of HEC and PVP enhanced the semi-solid nature of the product, resulting in decreased product elasticity and cohesiveness. Several statistically significant interactions between polymeric formulation components were observed within the factorial design, with respect to rate of release and all mechanical properties. These interactions arose because of variations in the physical states (dissolved or dispersed) of polymeric formulation components. Conclusions. The optimal choice of bioadhesive formulation for use in periodontal disease will involve a compromise between achieving the necessary release rate of tetracycline and the mechanical characteristics of the formulation, as these factors will affect clinical efficacy and the ease of product application into the periodontal pocket.     

EEG effects of physostigmine and choline chloride in humans

Seventeen normal volunteers received either 0.5 mg, 1.5 mg, or 2.5 mg physostigmine i.v. in a placebo-drug-placebo single-blind design. EEG was recorded simultaneously and analyzed by computerized spectral analysis. Eleven healthy elderly volunteers (mean age=69.1 years) with mild memory impairment were treated with placebo, followed by oral choline chloride (either 8 g/day for 3 weeks, or 16 g/day for 1 week), and then, again, placebo. Recordings of spontaneous EEG and EEG event-related potentials (contingent negative variation) were obtained during both placebo and choline treatments. The larger doses of physostigmine produced an increase in low frequency activity and a slowing of the peak alpha frequency. Oral choline chloride had no effect on the EEG as measured by spectral analysis, but appears to have differential effects on contingent negative variation (CNV) amplitude and reaction time, depending upon the initial CNV amplitude.     

Cells of origin and terminal distribution of corticostriatal fibers arising in the sensory-motor cortex of monkeys.

The cells of origin of the corticostriatal projection have been identified in squirrel monkeys by the use of the retrograde horseradish peroxidase method. In the subfields of the somatic sensory, motor, parietal and frontal areas of the cortex, cells projecting to the ipsilateral striatum are relatively sparsely distributed and form a group of small- to medium-sized pyramidal cells with an average somal diameter from area to area of 14-16 mum. Such cells are found only in layer V of the cortex (mainly in the more superficial parts of the layer). Since they are consistently smaller than the pyramidal cells of layer V that project to the brainstem and spinal cord and since they lie outside layer VI which gives rise to corticothalamic axons, the corticostriatal axons are unlikely to be collaterals of axons projecting to other sites. The cells of origin of the crossed corticostriatal projection are also found in layer V and are pyramidal cells with somal diameters in the same range as above. They are found only in areas 4, 8, and 6. Studies with the anterograde, autoradiographic method in rhesus, cynomologous and squirrel monkeys, indicate that the somatic sensory areas project to most of the antero-posterior extent of the ipsilateral putamen. Subareas 3a, 3b, 1 and 2 of the somatic sensory cortex project to the same region and the projection overlaps similarly extensive projections from the motor and certain other areas of the cortex. However, in each case the pattern of terminal labeling is in the form of interrupted clusters, strips and bands. A single small injection of the cortex is associated with only one or two such clusters of terminal labeling. This seems to imply that individual corticostriatal fibers end in a very restricted manner and that the terminal ramifications of fibers from one cortical area may alternate in the putamen with those arising in other areas.     

A longitudinal analysis of unmet need for oral treatment in a national sample of medical HIV patients

This longitudinal study examines perceived unmet dental need in a nationally representative probability sample of HIV-infected persons in medical care. A logistic regression analysis modeled the relationship between unmet need and explanatory variables. We estimate that 40% of HIV/AIDS patients report an unmet need associated with being male, being unemployed, injecting drugs, being heterosexual, lacking dental insurance, and having less education. Disparities in unmet need are related to socioeconomic status rather than to disease stage or ethnicity.     

Flow-mediated vasodilation predicts the presence and extent of coronary artery disease assessed by stress thallium imaging

BACKGROUND: Endothelial function can be measured by flow-mediated vasodilation (FMD) of the brachial artery and has been associated with cardiac risk factors (RF) and angiographically defined coronary artery disease (CAD). Stress single photon emission computed tomography (SPECT) imaging is commonly used to study patients with CAD. We sought to study the relationship between endothelial dysfunction by FMD and stress thallium SPECT to detect CAD. METHODS AND RESULTS: Fifty-five consecutive patients with chest pain syndrome referred for stress SPECT and eleven healthy control subjects had FMD measured on the brachial artery by standard techniques. The main outcome was the percent of brachial artery diameter dilation from baseline and the number of perfusion defects by SPECT. In subjects with no RF, those with RF but no defects, and those with defects, the mean FMD was 18.88% +/- 2.31%, 7.85% +/- 1.66%, and 5.91% +/- 1.07%, respectively (P < .05). A significant correlation was found between the number of thallium defects and degree of FMD impairment (r = -0.40, P < .01). An FMD cutoff value of less than 7.5% had a 72.5% sensitivity and 73.1% specificity in predicting the presence of any thallium defects. After RF adjustment, FMD remained as the strongest predictor of scintigraphic CAD (odds ratio, 10.96; 95% confidence interval, 2.82-57.31). CONCLUSION: FMD independently predicts the presence and extent of scintigraphic CAD.     

Spinal projections from the midbrain in monkey.

Neurons descending from the midbrain to the spinal cord in the monkey were identified with the retrograde horseradish peroxidase technique. Beginning in the caudal midbrain and extending anteriorly beneath the superior colliculus, large numbers of neurons of the nucleus cuneiformis and lateral central gray were found to project ipsilaterally to the spinal cord. In the posterolateral superior colliculus, neurons of the intermediate and deep layers, stratum griseum intermediale and stratum griseum profundum, were found to give rise to contralateral projections to the upper cervical spinal segments. An ipsilateral tectospinal projection from the anteromedial part of the collicus may also exist. In the red nucleus, neurons of the magnocellular division were shown to give rise to a somatotopically organized projection to the upper cervical cord and spinal enlargements. No neurons of the parvocellular red nucleus were labeled from the spinal cord. In the anterior midbrain, neurons of the interstitial nucleus of Cajal, nucleus of Darkschewitsch, and the adjacent dorsomedial and ventromedial midbrain tegmentum were found to give rise to an extensive ipsilateral descending spinal projection. Neurons located in various midline nuclei including the supratrochlear nucleus, oculomotor nucleus, Edinger-Westphal nucleus, and the ventral part of the central gray were also labeled from the spinal cord. These findings indicate that the primate midbrain is the origin of an extensive system of descending spinal pathways, some of which are likely to be involved in mediating descending influences involved in complex motor and sensory behavior.     

Ward nurses' evaluation of critical care outreach

Following the recommendation to introduce critical care outreach, two different models on two hospital sites were introduced within a large teaching Trust. To establish ward nurses' views and opinions of important components of the two outreach models, a questionnaire survey was undertaken involving 134 ward nurses on the awareness of outreach, accessibility of outreach and usage of outreach. The results identified a high level of user satisfaction amongst ward nurses. Awareness of critical care outreach and how to access the service within a hospital site was good, with little differences between the two different models. Outreach was found to provide ward nurses with better skills, more knowledge, advice and support. Providing a 24-h service and continual critical care education and training opportunities are the suggested ways to improve outreach in the future.     

Disturbance of vision by COX-2 inhibitors

In this review, 35 cases of acute, reversible, sometimes severe, disturbances of vision closely associated with the use of celecoxib or rofecoxib are described. These were identified from three different databases using strict selection criteria. The events included temporary blindness, visual field defect, scotoma, teichopsia, blurred vision, decreased vision and abnormal vision. The reactions had a mean onset time of 9.5 days and recovery occurred within 3 days following withdrawal of the drug. The reactions do not appear to be related to age, gender, dose, or indication for use. The incidence of reported cases is estimated to be not less than 5 per 10,000 patients. Possible mechanisms for this type of reaction are described. The most likely appears to be the result of interference with the retinal blood supply through reduced production of prostanoids. Genetic polymorphisms that affect drug metabolism or uptake could be risk factors and are discussed along with suggestions for research.