MgNd2 alloy in contact with nasal mucosa: an in vivo and in vitro approach.

Biodegradable and biocompatible magnesium alloys appear to be very promising not only for temporary clinical application but also for developing deformable and degradable medical implants. This study analyzes the in vivo degradation behavior and the impact on the paranasal sinuses of the highly ductile Mg-2 wt%Nd alloy (MgNd2) in order to provide a basis for a satisfying stent system for the therapy of a chronic sinusitis. Moreover, in vitro tests were carried out on primary porcine nasal epithelial cells (PNEC). For the in vivo tests, cylindrical MgNd2 specimens were implanted into the sinus' mucosa of minipigs. During and after a total period of 180 days the long-term biodegradation and biocompatibility properties after direct contact with the physiological tissue were analyzed. Biodegradation was investigated by measuring the mass and volume losses of the MgNd2 specimens as well as by performing element analyses to obtain information about the degradation layer. The influence on the surrounding tissue of paranasal sinuses was evaluated by endoscopic and histopathological examinations of the mucosa. Here, only a locally unspecific chronic infection was found. The degradation rate showed a maximum after 45 days postsurgery and was determined to decrease subsequently. In vitro experiments using PNEC showed adequate biocompatibility of MgNd2. This study demonstrates a good in vivo biocompatibility for MgNd2 in the system of paranasal sinuses and underlines the promising properties of alloy MgNd2 for biodegradable nasal stent applications.

A novel biodegradable frontal sinus stent (MgNd2): a long-term animal study.

The frontal sinus recess consists of anatomically narrow passages that are prone to stenosis in endonasal frontal sinus surgery for chronic sinus disease. Over the past 100 years, diverse frontal sinus stents have been developed and evaluated in clinical and animal studies. However, superinfection, formation of granulations tissue, stent dislocation and late stenosis of the duct have remained challenges and subject of debate in the literature. Currently developed biodegradable materials, including rare earth-containing magnesium alloys are promising candidates for application as temporary implant materials. The Mg 2 % wt Nd alloy (MgNd2) was used to design a nasal stent that fit the porcine anatomy. In the current study, we evaluate biocompatibility, biodegradation and functionality of a frontal sinus stent in 16 minipigs over 6 months. Intraoperative endoscopy revealed free stent lumen in all cases. Blood examination and clinical examinations indicated no systematic or local inflammation signs. The histopathology and elements analysis showed a very good biocompatibility. The µ-computed tomography-based volumetric analysis showed substantial stent degradation within 6 months. Our MgNd2 based stent appears to be a promising, solid basis for the development of a frontal sinus stent for clinical use.

Localization of synucleins in the mammalian cochlea.

Synucleins are widely expressed synaptic proteins within the central nervous system that have been implicated in such neurodegenerative disorders as Parkinson's disease. In this study, an initial characterization of all three synucleins, alpha-, beta-, and gamma-synuclein, within the cochlea was undertaken. Reverse transcriptase-polymerase chain reaction (PCR) demonstrated all three synuclein mRNA species within microdissected cochlear tissue. Quantitative PCR suggests that beta-synuclein is the most abundantly expressed form, followed by gamma- and then alpha-synuclein. Western blot analysis similarly demonstrates all three synuclein proteins within microdissected cochlear tissue. Immunofluorescence localizes the three synucleins predominantly to the efferent neuronal system at the efferent outer hair cell synapse, with some additional localization within the efferent tunnel-crossing fibers (alpha- and gamma-synuclein), spiral ganglion (beta-synuclein), inner spiral bundle (gamma-synuclein), and stria vascularis (alpha- > beta-synuclein). Developmentally, gamma-synuclein can be seen in the region of the outer hair cells by E19, while alpha- and beta-synuclein do not clearly appear there until approximately P10. Additional studies in a null-mutant gamma-synuclein mouse show no histological changes in the organ of Corti with normal hair cell and spiral ganglion cell counts, and normal ABR and DPOAE thresholds in wild-type vs mutant littermates. Together, these results localize synucleins to the efferent cholinergic neuronal auditory system, pointing to a role in normal auditory function, and raising the potential implications for their role in auditory neurodegenerative disorders. However, gamma-synuclein alone is not required for the development and maintenance of normal hearing through P21. Whether overlapping roles of the other synucleins help compensate for the loss of gamma-synuclein remains to be determined.

Restricted heterogeneity and T cell dependence of human thyroid autoantibody immunoglobulin G subclasses.

Twenty-five sera from patients with autoimmune thyroiditis, positive for thyroglobulin (hTg) and/or thyroid microsomal autoantibodies (M-Ab), were assessed by specific micro-ELISA to determine thyroid autoantibody immunoglobulin G (IgG) subclass distribution. Of the 25 sera, 22 were positive for M-Ab. All but 1 sample had restricted heterogeneity confined to IgG1 and/or IgG4 subclasses. The contribution of each subclass to an individual autoantibody titer varied from 100% IgG1 to 100% IgG4. Sixteen of the 25 sera had detectable hTg-Ab, and the majority also were restricted to IgG1 and IgG4, with similar distributions occurring among subclasses. In all, only 5 sera had hTg/M-Ab in IgG subclasses 2 and/or 3. T cell control of pokeweed mitogen-stimulated IgG subclass secretion was analyzed using increasing numbers of T cells in ratios of T to non-T from 0:1 to 10:1. In normal subjects, IgG1, but not IgG 2, 3, or 4, had T cell dependence, as evidenced by enhancement and inhibition of IgG1 secretion as the number of T cells increased. T cell suppressor dysfunction was apparent in patients with autoimmune thyroiditis, as demonstrated by the reduced ability of patient T cells (n = 6), compared with normal T cells (n = 6), to suppress total IgG1 subclass secretion. These data indicate 1) restricted heterogeneity of human thyroid autoantibodies, principally to IgG1 and IgG4; 2) T cell dependence of only IgG1 secretion in vitro; and 3) a T cell defect in patients with autoimmune thyroid disease. The possibility of IgG4 thyroid autoantibodies being under less stringent T cell regulatory control questions the likely importance of thyroid-specific suppressor T cell dysfunction in the etiology of autoimmune thyroid disease.

Impact of spirituality and religiousness on outcomes in patients with ALS.

The Project of Death in America Study at Columbia Presbyterian Medical Center enrolled 121 patients with ALS from 1996 through 1997, 46 of whom participated in a study assessing the effects of religiousness and spirituality (attachment to life, mental health, support group, health care proxy, and attitudes toward death) on outcomes (technology and death). Spirituality or religion influenced use of percutaneous endoscopic gastrostomy, noninvasive assisted ventilation, tracheotomy, and attitudes toward the dying process.

Relationship between amplitude of tremor and reflex responses of the human jaw-closing system.

Jaw-closing force was transduced while subjects maintained a biting force of 9.8 N. To estimate the amplitude of tremor in each subject's force record, the average spectrum of the force was computed, and the definite integral of the averaged spectrum in the frequency range from 3.5 to 10 Hz was calculated. For the same subjects, the amplitude of reflex responses to innocuous mechanical stimuli delivered to intraoral and perioral sites was measured as the peak-to-peak change in jaw-closing force following application of the stimulus. Force responses produced by stimulation at each site were used to compute an average reflex response measure for each subject. Large intersubject variability was observed in the amplitudes of jaw tremor and reflex responses. A correlation coefficient computed between the tremor and reflex measures revealed that subjects with large amplitude tremor tended also to have large reflex force responses. This correlation is consistent with the suggestion that activity in cutaneous reflex pathways contributes to tremor of the human mandible.

A needs assessment for a palliative care curriculum.

To ensure the success of a new curriculum at an institution, information about the educational needs of learners, available resources, and potential obstacles needs to be systematically collected and analyzed prior to the development and implementation of the actual curriculum. This process, known as needs assessment, is important in the development of palliative care training for internal medicine residents, because internal medicine has only recently begun to address these issues in a formalized way and palliative care is a relatively new topic in medical education and clinical medicine. Therefore, institutional issues and resistance, lack of knowledge and appropriate attitudes among trainees and faculty, and a paucity of educational models for individual internal medicine training programs present potential obstacles. Although curricula that have been developed by national organizations can serve as "guideposts, " these documents are unable to address the specific needs and culture of an individual institution. This paper outlines a systematic methodology of needs assessment for palliative care curricula at individual institutions that could be applied to the development and implementation of palliative care training for different groups of learners. An institution-specific needs assessment was developed based upon the findings of a systematic literature review and interviews with experts in palliative medicine and medical education. The following methods were utilized: 1) an anonymous survey; 2) focus groups; 3) topic rankings; and 4) individual interviews. The needs assessment revealed the following educational, clinical, and institutional information: 1) interns had very little exposure to palliative care in medical school; 2) there was no formalized system formal education and clinical exposure; 3) tremendous interest in palliative care education existed; 4) patients, families, physicians, and nurses perceived a need to improve the quality of palliative care; and 5) there are several political, logistical, and resource (time and financial) obstacles that needed to be addressed. An institution-specific needs assessment is an important part of the successful development and implementation of any new curriculum for medical residents and was specifically necessary for our palliative care program. As a result of the needs assessment process, a curriculum consisting of ten units of case-based and problem-based teaching was successfully implemented.

Reflex responses of human lip muscles to mechanical stimulation during speech.

The role played by reflex pathways in the production of movement has been a significant issue for motor control theorists interested in a wide variety of motor behaviors. From studies of locomotion and chewing, it appears that gains in reflex pathways can be altered so that activity in these pathways does not produce destabilizing responses during movement. In speech production, recent experimental evidence has been interpreted to suggest that autogenetic lip reflexes (perioral reflexes) are suppressed during sustained phonation or speech production. The present study was conducted to assess the effects of phonation, direction of movement, and ongoing speech production on reflex responses of lip muscles. The present results suggest, in contrast to earlier work, that this reflex pathway is not suppressed or absent because the amplitude of the observed response depends upon the activation levels of the various muscles of the lower lip and, therefore, indirectly on the nature of the gesture the subject is instructed to produce.

Acute red eye. Differentiating viral conjunctivitis from other, less common causes.

Adenoviral conjuctivitis is one of the most common causes of acute red eye. Other diagnostic considerations include herpes virus conjunctivitis, chlamydial conjunctivitis, allergic conjunctivitis, and various other less common infections. Careful history taking can help in identifying a viral cause. The presentation may range from a minor conjunctivitis resulting from an upper respiratory tract infection to a serious, debilitating epidemic keratoconjunctivitis. Local care and interventions to minimize transmission are the cornerstones of management. Infection is usually self-limiting. Warm soaks and artificial tear lubricants may relieve itching and burning. Patients should be instructed to avoid touching their eyes, wash hands often, use disposable towels, and avoid group activities for as long as an ocular discharge is present. Use of topical corticosteroids or antibacterial preparations can lead to complications, and injudicious use of topical corticosteroids may mask serious conditions that require other interventions.

Autonomic correlates of stuttering and speech assessed in a range of experimental tasks.

Electrodermal activity, peripheral blood flow, and heart rate were recorded from 19 stutterers and 19 normal speakers during performance of jaw movements, a strenuous breath-holding task, reading, and spontaneous speech. The tasks were selected to produce a range of autonomic activation and thus help scale autonomic activation for speech relative to other motor behaviors. Speaking was associated with relatively large increases in autonomic activity in both stutterers and normal speakers. There were no differences between the two groups of speakers, suggesting that the stutterers did not have abnormally high levels of autonomic activation in speech. Within the group of stutterers, the more extreme increases in arousal (specifically increases in measures reflecting sympathetic arousal) were correlated with the occurrence and increased severity of disfluent speech. Significant correlations were found for the intervals prior to, during, and after speech. Although significantly correlated with disfluency, measures of autonomic arousal accounted for small percentages of the variances of fluency and severity. The results are consistent with the hypothesis that sympathetic arousal accompanies the breakdowns in speech motor processes characteristic of stuttering. Mechanisms linking autonomic nervous system functions and somatic sensorimotor processes involved in speech production are discussed.

Reflex responses in human jaw, lip, and tongue muscles elicited by mechanical stimulation.

Reflex responses in human jaw, lip, and tongue muscles were elicited with brief, innocuous mechanical stimuli. Stimuli were applied to the masseter (and overlying tissue), the lower lip vermilion, and the tongue dorsum. Reflex responses occurred in masseter, orbicularis oris inferior, and genioglossus muscles upon direct stimulation of the sites associated with each of these muscles. In contrast, reflex responses to stimulation of "distant" sites occurred almost exclusively in masseter; that is, stimulation of the lip and tongue produced responses in masseter, but, stimulation of jaw muscle spindle afferents and overlying cutaneous receptors had no observable effect on activity in genioglossus or orbicularis oris inferior muscles. It could be hypothesized that the motoneuron pools controlling jaw muscles are more sensitive to synaptic inputs generated by reflex pathways originating in other structures. The sensitivity of the masseter muscle to inputs from the lip and tongue may serve to link these structures functionally.

Case management for persons who are homeless.

Comprehensive, client-centered continuous care with a multidisciplinary team using the case management model has proven to be essential in providing health care services to the homeless. Despite their heterogeneity, homeless persons share the common experiences of being poor, isolated, and in crisis. The process of case management is inherently therapeutic for its recipients and providers. It has the potential to be a source of human support for those who have none. Case management models can be effective systems for providing health care to these persons while addressing their special needs and characteristics.

Developmental and age-related changes in reflexes of the human jaw-closing system.

Reflex responses of the jaw-closing system to innocuous mechanical stimulation of the tongue and palate were examined in a group of 25 girls aged 7-8 years and in a group of 25 women aged 70-80 years. Responses were measured both as changes in background biting force and from bilateral recordings of masseter EMGs. For comparative purposes, results from an earlier study of 35 young adult women (aged 18-25 years) were available. Compared to younger groups of subjects, reflex responses of the elderly were reduced in numbers and amplitude, were characterized by fewer initial excitatory component responses, and had longer latency to onset. Analyses of responses of the children indicated that age 7-8 years is a transitional period. Some children show adult-like responses, while others display responses that appear to represent earlier forms or transitional responses. These results suggest that oral-motor reflexes are not fixed response patterns upon which more complex motor skills, such as speech, are built. Rather, oral reflex development appears to occur in concert with the acquisition of complex motor skills. Systematic changes in reflex responses also occur in the period from young adulthood to seventh decade of life. This result indicates a continuous evolution of oral sensorimotor systems throughout the human life span.

Biliverdin reductase is heat resistant and coexpressed with constitutive and heat shock forms of heme oxygenase in brain.

Two heme oxygenase (HO) isozymes--HO-1, which is a heat shock protein (HSP32), and HO-2--catalyze the isomer-specific production of biliverdin IX alpha and carbon monoxide. The latter has the potential of functioning as a neurotransmitter, whereas the reduced form of biliverdin, bilirubin, has potent antioxidant activity. Formation of bilirubin is catalyzed by biliverdin reductase (BVR). The reductase is a unique enzyme in being dual pyridine nucleotide and dual pH dependent. Here, we show that the reductase is resistant to thermal stress at both the protein and message level. We further demonstrate that the reductase is coexpressed in cells that display HO-1 and/or HO-2 under normal conditions, as well as in regions and cell types that have the potential to express heat shock-inducible HO-1 protein. Exposure of male rats to 42 degrees C for 20 min did not decrease brain BVR activity, but caused a slight increase in NADPH- and NADH-dependent activities at 1 and 6 h following hyperthermia. High levels of the approximately 1.5-kb BVR mRNA were detected in control brain; it too displayed thermal tolerance. Similarly, the pattern of multiplicity of net charge variants of the enzyme purified from brain of heat-shocked rats did not differ from the control pattern. Immunochemical localization of BVR protein in normal brain correlated well with the presence of HO-1 and/or HO-2 throughout the forebrain, diencephalon, cerebellum, and brainstem regions. There were select neuronal and nonneuronal cells in the substantia nigra and cerebellum that did express the reductase under normal conditions, wherein no HO isozymes could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between speech and finger movements: an exploration on the dynamic pattern perspective.

Under the dynamic perspective for motor control, movement is viewed as an "emergent" property, arising from cooperative relationships among limit-cycle oscillators. This is in contrast to more traditional approaches to motor control in which a central representation of movement is usually assumed to exist. The assertion that coordination of movement arises from interactions between oscillatory processes leads to some unexpected predictions. In particular, interactions between frequency and amplitude of simultaneously performed speech and manual tasks are predicted, because the organism "parameterizes" all ongoing oscillatory processes as a "total unit." Using quantitative analyses, we have demonstrated that interactions between speaking and finger tapping do occur in both the amplitude and frequency domains. Such interactions, however, do not appear to be as simple as those predicted by proponents of the dynamic pattern perspective.

Corticosterone regulates heme oxygenase-2 and NO synthase transcription and protein expression in rat brain.

Heme oxygenase (HO)-1 and -2 produce carbon monoxide, which is suspected, as is nitric oxide (NO), to function as a neuronal messenger. We report on glucocorticoid-mediated modulation of HO-2 and NO synthase expression in brain and the differential response of the two proteins to corticosterone in different brain regions. Corticosterone treatment (40 mg/kg, 20 days) had opposing effects on HO-2 and NO synthase transcript levels: increasing the 1.3- and 1.9-kb HO-2 mRNAs and decreasing that of the brain-specific 10.5-kb NO synthase. Corticosterone did not uniformly affect HO-2 protein expression in all regions, but appeared to cause a universal reduction in NO synthase, e.g., HO-2 was decreased in hippocampus (CA1 and dentate gyrus), but not in cerebellum. In contrast, NADPH diaphorase staining was reduced in hippocampus and in molecular and granule layers of cerebellum (not detected in Purkinje cells). Striking deficits in neuronal morphology and number of diaphorase-staining neurons were observed in the lateral tegmental area, paraventricular nucleus, and frontal cortex; HO-2 expression was only selectively affected. In cerebellum, activity of NO synthase, but not that of HO, was reduced. Consistent with the possibility that carbon monoxide can generate cyclic GMP, the change in cyclic GMP level did not mirror the decrease in NO synthase. We suggest that glucocorticoid-mediated deficits in hippocampal functions may reflect their negative effect on messenger-generating systems.

Spatial organization of human perioral reflexes.

Reflex responses recorded from the upper and lower divisions of the human orbicularis oris muscle were studied as a function of the site of stimulation. Stimuli were applied to 11 sites, ranging from the glabrous skin of the upper and lower lip vermilion borders to the hairy skin of the cheek. Highly localized, innocuous mechanical stimuli were created by displacing a servo-controlled probe over the surface of the perioral skin. Reflex response amplitude was strongly dependent on the site of stimulation. Stimulation of some sites, for example the ipsilateral corner of the mouth, the chin, and cheek, produced no responses, whereas stimulation of other sites, particularly the ipsilateral vermilion borders, produced large reflex responses. Changes in response amplitude as a function of stimulation site were the same for the upper lip and lower lip muscle recordings, with the largest responses at both recording sites produced by stimulation of the ipsilateral upper lip vermilion border. These results suggest that the upper and lower divisions of orbicularis oris share common synaptic drive, at least from inputs generated via reflex pathways, and that the upper vermilion border may be more densely innervated with mechanoreceptors than the lower. The latter hypothesis was supported by an additional experiment examining two-point discrimination thresholds for the glabrous skin of the upper and lower lips. Two-point thresholds were significantly smaller for the upper compared with the lower lip vermilion border.

Reflex responses of the human jaw-closing system depend on the locus of intraoral mechanical stimulation.

Innocuous mechanical stimuli were applied to eight sites on the tongue dorsum and palate while subjects used feedback to maintain a constant isometric biting force. Reflex responses of the jaw-closing system were measured as changes in force and in EMGs recorded from right and left masseter muscles. Stimulation at each of the eight sites produced reflex force and EMG responses in most subjects tested. The nature of the reflex responses strongly depended on the site of stimulation. Stimulation of the palate tended to produce suppression of ongoing EMG activity and decreases in background biting force. In contrast, stimulation of sites on the tongue posterior to the tip, most often resulted in excitatory EMG responses and increases in jaw-closing force. Unilateral, early excitatory responses were observed in the right masseter with stimulation of the right side of the tongue. The existence of spatially organized responses of the human jaw-closing system to innocuous intraoral stimulation is not consistent with the view that these cutaneous reflexes are primarily of protective significance.

Corticosterone has a permissive effect on expression of heme oxygenase-1 in CA1-CA3 neurons of hippocampus in thermal-stressed rats.

Activity of the stress protein, heme oxygenase-1 (hsp32; HO-1), produces carbon monoxide (CO), the potential messenger molecule for excitatory N-methyl-D-aspartate receptor-mediated events, in the hippocampus. Long-term stress caused by elevated adrenocorticoids induces pathological changes in CA1-CA3 neurons of the hippocampus; the adrenal hormones also exacerbate damage from stress. In rats chronically treated with corticosterone, we examined expression of HO-1 and its response to thermal stress in the hippocampus. An unprecedented appearance of scattered immunoreactive astrocytes marked the molecular layer of the hippocampus in corticosterone-treated rats. Steroid treatment showed no discernible effect on whole-brain HO-1 mRNA. When these rats were subjected to hyperthermia, neurons in the CA1-CA3 area, including pyramidal cells, exhibited intense immunoreactivity for the oxygenase and a pronounced increase (approximately 10-fold) in number. HO-1 is essentially undetectable in this area when rats are exposed to chronic corticosterone alone or thermal stress by itself, or in control rats. In contrast, similar analysis of hilar neurons showed no apparent effect on either the number or relative intensity of HO-1-immunostained cells after treatment. Corticosterone treatment also intensified the stress response of cerebellum, including Purkinje cells and Bergmann glia in the molecular layer. In brain, despite a pronounced reduction in NO synthase activity in corticosterone-treated and/or heat-stressed animals, the level of cyclic GMP was not significantly reduced. These observations are consistent with the hypothesis that responsiveness to environmental stress of CA1-CA3 neurons brought about by chronic elevation in circulating adrenocorticoids results in an increased excitatory neuronal activity and eventual hippocampal degeneration. Moreover, these findings yield further support for a role of CO in the production of cyclic GMP in the brain.