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Biomedical subjects

H R Konrad

Publications and source records attributed to H R Konrad.

At least 19 recordsLinked to original sources

Age-related changes in levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2 in the rat inferior colliculus: implications for neural senescence.

Brain-derived neurotrophic factor and fibroblast growth factor 2, and their respective binding sites, tyrosine kinase B receptor and fibroblast growth factor receptor 2, are known to regulate neurite outgrowth and antioxidant enzyme activity. Several studies suggest that brain-derived neurotrophic factor and fibroblast growth factor are contained in the inferior colliculus. Previous work in our laboratories revealed dendritic and synaptic losses in the inferior colliculus of aged Fischer-344 rats, along with coincident increases in lipid peroxidation possibly linked to a decrease in activity of antioxidant enzymes. In an effort to identify potential causal mechanisms underlying age-related synaptic and dendritic losses that occur in the inferior colliculus, the present study attempted to determine if inferior colliculus levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2 expression are altered with age. Immunocytochemistry was performed in the inferior colliculus, hippocampus and cerebellum of 3-month-old F344 rats to study distributions of the full-length and truncated isoforms of tyrosine kinase B receptor, and fibroblast growth factor receptor 2. The latter two brain regions served as positive controls. For all three antigens, immunolabeling was localized primarily in somata and proximal dendrites in all subdivisions of the inferior colliculus, and in the dentate gyrus and Ammon's horn of the hippocampus. In the cerebellum, the somata and dendrites of the Purkinje cells were also immunolabeled.A significant reduction in levels of the full-length form of tyrosine kinase B receptor in 18- and 25-month-old rats (respectively, approximately 20% and 30% relative to 3-month-olds) was revealed using western blot analyses. Inferior colliculus and hippocampal levels of the truncated form were modestly decreased ( approximately 7%) as well in the two older age groups. In contrast, levels of fibroblast growth factor receptor 2 in the inferior colliculus and hippocampus were elevated by approximately 35% in the two older age groups when compared to 3-month-olds. Changes in cerebellar levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2, while similar to those in the inferior colliculus and hippocampus among the age groups, did not achieve statistical significance in this study. These findings give rise to the possibility that age-related reductions in tyrosine kinase B receptor levels could be a causal factor in the degenerative changes observed in the inferior colliculus of aged animals, including mitochondrial damage and dendritic regression. The observed increases in fibroblast growth factor receptor 2 levels may be compensatory to the increased oxidative stress. The effectiveness of the fibroblast growth factor receptor 2 response is questionable given the damage that occurs in the inferior colliculus and hippocampus of aged animals. However, the deficits could worsen in the absence of an increase in fibroblast growth factor receptor 2.

Aging↗

Predicting fall risks in an elderly population: computer dynamic posturography versus electronystagmography test results.

OBJECTIVES/HYPOTHESIS: Falls are the leading cause of morbidity and mortality for persons aged 65 years and older, with more than 2 million people falling and sustaining serious injury annually. This study compared computer dynamic posturography (CDP) and electronystagmography (ENG) results as predictors of falls. STUDY DESIGN: Retrospective. METHODS: Thirty-three patients over the age of 65 years who presented to a balance disorders and falls prevention clinic were used for this study (22 women and 11 men, with an average age of 78.0 y and a mean fall rate of 3.5 times). All had experienced at least one fall in the year before visiting the clinic and were tested with both CDP and ENG. The CDP results were divided into subcategories (sensory organization testing and limits of stability); ENG results were divided into four categories (ocular motor, rotational chair, positional, and caloric studies). RESULTS: Test findings were classified as normal or abnormal based on age-matched normative data. Of the patients in the study, 27.3% were normal for one type of testing and abnormal for the other. Twenty-six patients (78.8%) had abnormal results on CDP, and 20 individuals (60.6%) showed ENG abnormalities (42.4% for ocular motor, 28.6% for positional, 13.6% for caloric, and 11.2% for rotational chair studies). The limits of stability category was significant in predicting multiple falls. CONCLUSION: For this population, CDP was determined to be a more sensitive test for identifying patients who have fallen, with limits of stability testing the most significant part of the CDP battery; for ENG studies, the best falls indicator was the ocular motor battery.

Accidental Falls↗

Age-related changes in [3H]strychnine binding in the vestibular nuclei of rats.

Glycine plays an important role as a neurotransmitter in the four vestibular nuclei (VN). The objective of this study was to determine if the levels of glycine-receptor binding in the VN change as a function of age. Quantitative receptor autoradiography was performed on brainstem sections from three age groups (3, 18 and 26 months) of Fischer 344 rats to assess binding in the VN. Glycine receptors were localized using [3H]strychnine binding. Strychnine binding declined monotonically with increasing age, such that the level of strychnine binding in each of the VN in the 28-month-old animals was approximately one-half that in the 3-month-olds. The age-related decrease in levels of strychnine binding suggest altered glycinergic function in the VN, which may in turn contribute to disturbances in equilibrium observed in the elderly.

Aging↗

Balance and aging.

OBJECTIVES/HYPOTHESIS: To provide a basic science and clinical review of normal balance changes with age, and to provide a current review for the evaluation and treatment of elderly patients with balance disorders. As we age, we lose balance function through loss of sensory elements, the ability to integrate information and issue motor commands, and because we lose musculoskeletal function. Diseases common in aging populations lead to further deterioration in balance function in some patients. Treatment of balance dysfunction in aging populations is based on the knowledge of normal aging processes and on an evaluation of the individual's balance loss and remaining balance elements. Prevention and rehabilitation play a major role in treatment; medical and surgical therapy also have a place. STUDY DESIGN AND METHODS: Review of literature, personal research and observations. RESULTS AND CONCLUSIONS: Although older patients may be subject to most of the common balance disorders of younger patients, they have more problems with chronic disequilibrium and falls. Prevention and rehabilitation play an important role in treating these patients.

Accidental Falls↗

Vestibular rehabilitation therapy for the patient with dizziness and balance disorders.

Vestibular disorders and balance dysfunctions affect a significant number of patients seeking treatment from otolaryngologists. Vestibular Rehabilitation Therapy (VRT) has been shown to be a highly efficacious treatment modality for a majority of individuals with vestibular or central balance system disorders, or a combined etiology. Assessment methods, treatment paradigms, and recommendations for referral are presented.

Adaptation, Physiological↗

Computerized dynamic platform posturography.

Computerized dynamic platform posturography is defined in this technology assessment. The review discusses what computerized dynamic platform posturography measures, what the reliability and validity of the information are, and the uniqueness of the information provided. The clinical contribution and indications for testing are discussed. There are comments on future directions for research on computerized dynamic platform posturography and a summary and conclusion.

Diagnostic Techniques, Neurological↗

Vestibular deficits in deaf children.

Considerable knowledge has been accumulated regarding acquired and congenital deafness in children. However, despite the intimate relationship between the auditory and vestibular systems, data are limited regarding the status of the balance system in these children. Using a test population of 15 children, aged 8 to 17 years, we performed electronystagmography testing. The test battery consisted of the eye-tracking (gaze nystagmus, spontaneous nystagmus, saccade, horizontal pursuit and optokinetic) tests, positional/positioning (Dix-Hallpike and supine) tests, and rotational chair tests. With age-matched controls, five children were tested in each of the following three categories: normal hearing, hereditary deafness, and acquired deafness. The children in the hereditary deafness category were congenitally deaf and had a family history of deafness. Those subjects in the acquired deafness category had hearing loss before the age of 2 years, after meningitis. Analysis of variance demonstrated significant differences between the two deaf groups and the control subjects in the gaze nystagmus test, saccade latencies, horizontal pursuit phase, and Dix-Hallpike and supine positionally provoked nystagmus. Also, significant differences were found in rotational chair gain and phase between the deaf and normal-hearing children. The children with acquired deafness exhibited the most profound results. In addition, there were significant differences in rotational chair gain between the acquired and congenitally deaf children. No differences were noted in horizontal pursuit gains, saccade accuracies, or saccade asymmetries. These preliminary data demonstrate that the etiologic factors responsible for congenital and acquired deafness in children may indeed affect the balance system as well. These findings of possible balance disorders in conjunction with the profound hearing loss in this patient population will have prognostic implications in the future evaluation, treatment, and rehabilitation of these patients.

Adolescent↗

Management of benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is one of the most common balance disorders of the peripheral vestibular system. Diagnosis is made from patient history and the manifestation of specific symptoms. Treatment differs for the individual patient and may include pharmacological, surgical, dietary, and/or therapeutic modalities. Various versions of Modified Liberatory Maneuvers (MLM), and other, similar rehabilitation therapy treatments have been shown to be very effective in the management of the BPPV patient.

Diagnosis, Differential↗

Scanning electron microscopic evaluation of age-related changes in the rat vestibular epithelium.

An ultrastructural study was performed to assess age-related changes in the vestibular end organs of Fischer 344 rats. The surfaces of the maculae and cristae from 3-, 12-, and 24-month-old Fischer 344 rats were observed by use of scanning electron microscopy. Age-related changes in the morphology of the vestibular neuroepithelium included a substantial loss of hair cells, as well as a reduction in the number of kinocilia and stereocilia on those that remained. These changes were greatest in the central upper regions of the three ampullae. In aged animals a greater area of the neuroepithelial surface was covered with microvilli, and in some instances, giant cilia were found among the microvillous surfaces. In contrast, there were few differences among the three age groups in the number and condition of hair cells in the saccules and utricles. The changes observed in the cristae may contribute to the age-associated impairment of vestibular function. If similar changes occur in human beings, these could in part account for the presbycusis observed in the elderly.

Acoustic Maculae↗

Rehabilitation therapy for patients with disequilibrium and balance disorders.

Vestibular rehabilitation is based on the use of adaptive and compensatory mechanisms already existing in the human brain. Research using animals provides a great deal of information on the neural mechanisms responsible for these functions and suggests strategies that should be helpful in rehabilitation of patients with disequilibrium and balance disorders. Research in animals and human beings suggests that rehabilitation should be specifically designed, depending on the patients' deficits. It also suggests that to be effective it needs to be started soon after impairment and that vestibulosuppressive medication may reduce recovery. Studies are now underway to evaluate the effectiveness of vestibular rehabilitation on several groups of patients and to answer some fundamental questions about the mechanisms and the effectiveness of these treatment methods. Current information suggests that vestibular rehabilitation is an effective method of therapy for many patients with disequilibrium and balance disorders and that for some patients it is the best therapy available.

Animals↗

Clinical application of saccade-reflex testing in man.

Computer-aided measurements of saccade-reflex reaction times, velocities, and accuracies have become important tools in the detection of central nervous system pathology. Because of improved knowledge of the reflex pathways in man, saccade testing can assist in differentiating between brain stem, cerebellar, or cerebral disorders and point toward unilateral lesions. Saccade-reflex testing is also useful in determining disability and measuring over time the course of central nervous system disorders. Further work, correlating lesions observed by high-resolution imaging techniques with abnormalities in reflexes, continues to improve the understanding of saccade mechanisms in man. Specific cases are used to show the effects of anatomic lesions on changes in saccade reflexes. The results from 100 consecutive patients evaluated for dizziness are provided in order to illustrate the prevalence of saccade abnormalities and the relationship between abnormalities in vestibular and slow and fast eye-movement reflexes. Patients complaining of disequilibrium and visual disturbances frequently have abnormalities in the saccade system, abnormalities which are often overlooked in present clinical testing of the dizzy patient.

Adolescent↗

Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements.

Twenty-nine patients with necrotizing fasciitis were treated from 1980 to 1988. This study evaluates how the addition of hyperbaric oxygen (HBO) therapy to surgical treatment has affected mortality and the number of debridements required to achieve wound control in these patients. Two groups of patients were viewed: group 1 (n = 12) received surgical debridement and antibiotics only; group 2 (n = 17) received HBO (90 minutes at 2.5 atm, average 7.4 treatments) in addition to surgery and antibiotics. Both groups were similar in age, race, sex, wound bacteriology, and antimicrobial therapy. Body surface area affected was similar, however, perineal involvement was more common in group 2 (53%) than in group 1 (12%). The admitting conditions of patients in group 1 (non-HBO) were diabetic, 33%; white blood cell count more than 12,000, 50%; and shock, 8%. The admitting conditions of patients in group 2 (HBO) were diabetic, 47%; white blood cell count more than 12,000, 59%; and shock, 29%. Although group 2 patients receiving HBO were more seriously ill on admission, mortality was significantly lower (23%) compared to group 1 (66%) (p less than 0.02). In addition, only 1.2 debridements per group 2 patient were required to achieve wound control versus 3.3 debridements per group 1 patient (p less than 0.03). The addition of HBO therapy to the surgical and antimicrobial treatment of necrotizing fasciitis significantly reduced mortality and wound morbidity (number of debridements) in this study, especially among nonclostridial infections. We conclude that HBO should be used routinely in the treatment of necrotizing fasciitis.

Adolescent↗