Identification of FDA-Approved Drugs and Bioactives that Protect Hair Cells in the Zebrafish (Danio rerio) Lateral Line and Mouse (Mus musculus) Utricle

The hair cells of the larval zebrafish lateral line provide a useful preparation in which to study hair cell death and to screen for genes and small molecules that modulate hair cell toxicity. We recently reported preliminary results from screening a small-molecule library for compounds that inhibit aminoglycoside-induced hair cell death. To potentially reduce the time required for development of drugs and drug combinations that can be clinically useful, we screened a library of 1,040 FDA-approved drugs and bioactive compounds (NINDS Custom Collection II). Seven compounds that protect against neomycin-induced hair cell death were identified. Four of the seven drugs inhibited aminoglycoside uptake, based on Texas-Red-conjugated gentamicin uptake. The activities of two of the remaining three drugs were evaluated using an in vitro adult mouse utricle preparation. One drug, 9-amino-1,2,3,4-tetrahydroacridine (tacrine) demonstrated conserved protective effects in the mouse utricle. These results demonstrate that the zebrafish lateral line can be used to screen successfully for drugs within a library of FDA-approved drugs and bioactives that inhibit hair cell death in the mammalian inner ear and identify tacrine as a promising protective drug for future studies.     

Nasopharyngeal pressure gradients during non-phonetic activities of the velopharyngeal valve. Part I

The phonetic activity of the velopharyngeal valve has been the subject of electromyographic, radiological, ultrasonic, endoscopic, and of various acoustic and aeromechanical investigations. The subject of the present study was the non-phonetic activities of the velopharyngeal valve. Ten patients were assessed by nasendoscopic examinations of the velopharyngeal valve. The pressure gradients in the nasopharynx during these activities were recorded. Typical individual nasopharyngeal pressure patterns were revealed inducing a development of a special technique and tests for a further study of the non-phonetic activities of the velopharyngeal valve in correlation with its abnormality and pathological speech activities.     

Anteroinferior plating of midshaft clavicular nonunions

Many different techniques have been reported for the treatment of clavicular nonunions. Those techniques involving screws and plate generally position the plate on the superior (subcutaneous) surface of the clavicle. To decrease the risk of screw pull-out and prominence of the instrumentation, we currently perform anteroinferior plating using a 3.5-millimeter pelvic reconstruction plate with a lag screw and bone graft. A consecutive group of twelve patients with midshaft clavicular nonunions was treated with this technique. All nonunions united after an average of 3.6 months (range 2 to 8 months). All patients regained full function and mobility of the shoulder. The technique as described in this article illustrates a successful modification of the traditional plating technique of midshaft clavicular nonunions. We conclude that anteroinferior plating is a reliable and safe technique that leads to high rates of bony union in midshaft clavicular nonunions.     

Phenotype markers and function of neutrophils in children with hemolytic uremic syndrome

The hemolytic uremic syndrome (HUS) is the most-common cause of acute renal failure in children. Several researchers have reported the presence of neutrophil (PMN) activating cytokines, such as interleukin-8 and tumor necrosis factor-α, in the sera of HUS patients. Moreover, PMN-derived products, such as elastase, were increased. These observations have lead to the hypothesis that activated PMN could act as mediators of endothelial damage. The objective of this investigation was to directly evaluate the activation status of peripheral PMN from children with HUS. For this purpose, 12 children with typical HUS were bled during the acute period, before dialysis and/or transfusion, and 8 of them were also bled after 1 month follow-up. Additionally, blood samples from healthy control children admitted for routine surgical procedures, chronic uremic children, and neutrophilic children with acute infections not related to HUS were collected and processed in an identical manner. The function and membrane activation markers of PMN from these groups were evaluated.We found that during the acute period of HUS, PMN had reduced expression of FcγRIII (CD16) and CD11b, were degranulated, and exhibited an impaired antibody-dependent cellular cytotoxicity. These parameters returned to normal after clinical recuperation. We conclude that PMN activation in HUS patients is a very early and transient event, and upon hospitalization before dialysis PMN show a phenotype and functional pattern of partial deactivation. Received: 25 June 2001 / Revised: 16 November 2001 / Accepted: 20 November 2001     

MR evaluation of crossed and uncrossed cerebral-cerebellar diaschisis

In three patients with infantile hemiplegia syndrome, MR imaging done later in life showed significant volume loss in the cerebellar hemisphere contralateral to the side of the affected cerebrum in two and ipsilateral in one. By comparison, the cerebellar volume loss seemed to correlate with the degree of volume loss in the contralateral cerebral hemispheres in two patients. These observations provide morphological evidence of the phenomenon of crossed and uncrossed/ipsilateral cerebral cerebellar diaschisis (CCD and ICD). Functional neuroimaging studies in support of the concept of CCD and ICD have been critically reviewed in the light of the morphological changes demonstrated in the cases cited herein.     

Crossed cerebral - cerebellar diaschisis: MRI evaluation

MRI, done later in life, in two patients with infantile hemiplegia syndrome showed significant volume loss in the cerebellar hemisphere contralateral to the side of the affected cerebrum. The cerebellar volume loss seemed to correlate with the degree of volume loss in the contralateral cerebral hemisphere. These observations provide morphological evidence of the phenomenon of crossed cerebral-cerebellar diaschisis (CCD). Functional neuroimaging studies in support of the concept of CCD has been critically reviewed.     

Population growth and collapse in a multiagent model of the Kayenta Anasazi in Long House Valley

Long House Valley in the Black Mesa area of northeastern Arizona (U.S.) was inhabited by the Kayenta Anasazi from about 1800 before Christ to about anno Domini 1300. These people were prehistoric ancestors of the modern Pueblo cultures of the Colorado Plateau. Paleoenvironmental research based on alluvial geomorphology, palynology, and dendroclimatology permits accurate quantitative reconstruction of annual fluctuations in potential agricultural production (kg of maize per hectare). The archaeological record of Anasazi farming groups from anno Domini 200-1300 provides information on a millennium of sociocultural stasis, variability, change, and adaptation. We report on a multiagent computational model of this society that closely reproduces the main features of its actual history, including population ebb and flow, changing spatial settlement patterns, and eventual rapid decline. The agents in the model are monoagriculturalists, who decide both where to situate their fields as well as the location of their settlements. Nutritional needs constrain fertility. Agent heterogeneity, difficult to model mathematically, is demonstrated to be crucial to the high fidelity of the model.