Epidermal growth factor suppresses renal tubular apoptosis following ureteral obstruction

Objectives. Acute unilateral ureteral obstruction (UUO) results in ipsilateral hydronephrosis characterized by a decrease in epidermal growth factor (EGF) mRNA expression and EGF protein levels in the distal renal tubules. UUO results in programmed cell death with increases in the characteristic markers of apoptosis. To suppress the apoptotic response during UUO, recombinant EGF was administered during renal obstruction and the ensuing molecular and histologic changes were studied.Methods. Mature Sprague-Dawley rats underwent left ureteral obstruction and the kidneys were harvested at 24, 48, and 72 hours. Markers of apoptosis included DNA laddering pattern on agarose gel electrophoresis, in situ gap labeling of fragmented DNA for quantitative apoptotic body determination, polyadenylated mRNA expression of SGP-2, and in situ hybridization for sulfated glycoprotein-2 (SGP-2) mRNA. Studies were repeated in rats following administration of 10, 20, and 40 μg of subcutaneous recombinant EGF on a daily basis after UUO.Results. Subcutaneous injection of EGF into unilaterally obstructed rats promotes renal tubular epithelial cell regeneration, as demonstrated by increased cortical mitotic activity. Systemic EGF supplementation in these unilaterally obstructed rats also resulted in a decrease in the intensity of the DNA laddering pattern associated with renal tubular apoptosis. An in situ labeling procedure to identify apoptotic nuclei in the ureterally obstructed kidneys revealed a 50% reduction in apoptosis after EGF administration. Northern blot analysis and in situ hybridization for SGP-2 mRNA or clusterin gene product also revealed a decreased expression in the obstructed and EGF-treated renal parenchyma.Conclusions. These data suggest that EGF, apart from its known role as a mitogenic substance for renal tubular epithelial cells, is also a critical in vivo renal cell survival factor for the developmentally mature kidney.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.     

Worldwide epidemiology and modes of transmission of delta hepatitis

Conclusions Since the discovery of HDV in 1977 byRizzetto and collegues (10), several studies regarding the pathogenesis, natural history and epidemiology of this infection have been accumulated. It emerges that HDV is an agent with unusual biologic properties which requires HBV replication for its expression. Given the obligatory association between HDV and HBV, transmission of HDV follows the same routes of HBV transmission. This implies that one expects HDV infection to be much more prevalent in countries with high HBsAg carrier rates. This is true in most areas of the world but not in Far East Asia. Endemicity of HDV is maintained in the community through the network of HBsAg carriers. HDV can be transmitted to HBV positive and negative individuals, but survives only after encountering the carrier. Recent outbreaks of severe epidemics of fulminant hepatitis due to HDV among the Yucpa Indians in Northern Venezuela, pointed out very clearly that HDV superinfection is an ominous risk for all populations where HBV is endemic.     

Occupational therapy workforce needs: a model for demand-based studies.

PURPOSE: To provide a model for assessing occupational therapy workforce needs by using a demand-based approach to determine current workforce status in the Northwest region. Regional information may have implications for addressing national occupational therapy service needs. METHOD: A questionnaire was sent to a proportional random sample of 234 facilities that hire occupational therapy practitioners. Data were collected in July-August 2003 using structured mailing and follow-up procedures. RESULTS: Response rate was 79%. Twenty-four percent reported occupational therapy vacancies and 11% occupational therapy assistant vacancies; 48% predicted an increase in occupational therapy positions in the next 2 years and 41% an increase in occupational therapy assistant positions. Sixty-three percent of respondents reported difficulty in hiring. DISCUSSION: This study identifies an occupational therapy workforce shortage in the Northwest. Management of a shortage is critical, for even short-term adjustments could lead to permanent changes in service provision. This study demonstrates the importance of current information on the status of the national workforce and serves as a model for future studies.     

Der Einsatz des Prophy-Jet®-Gerätes zur Schmelzpolitur nach der Bracketentfernung

Zusammenfassung In einer In-vitro-Studie wurde die Einsatzfähigkeit des Prophy-Jet-^®-Gerätes für die Schmelzpolitur nach Bracketentfernung untersucht. In die Studie wurden drei verschieden stark gefüllte orthodontische Kleber einbezogen: Concise^®, Genie^® und Mono Lok^®. Alle Proben wurden rasterelektronenoptisch untersucht und fotografisch dokumentiert in Vergrößerungen zwischen 20- und 10 000fach. Die Oberflächenanalyse ergab, daß das Prophy-Jet^®-Gerät allein zur Schmelzpolitur nach Bracketentfernung nicht ausreicht, um unter klinisch vertretbarem Zeitaufwand (1 Minute/Zahn) eine kunststofffreie Schmelzoberfläche zu erzielen. Nach konventioneller makroskopischer Vorreinigung mit Scalern oder rotierenden Hartmetallfinierern zeigten sich nach fünfsekündiger Prophy-Jet^®-Bestrahlung noch geringe Kleberreste. Nach zehnsekündiger Expositionsdauer waren beim Mono Lok^®-Adhäsiv keine Kleberreste mehr nachweisbar, beim Concise^®-bzw. Genie^®-Adhäsiv fanden sich noch vereinzelte geringe Kleberinseln. Das Prophy-Jet^®-Gerät erscheint zur Unterstützung der Schmelzpolitur nach Bracketentfernung sinnvoll; eine sorgfältige Vorreinigung mit Hand- oder rotierenden Instrumenten ist jedoch erforderlich, um eine weitgehende Adhäsivreduktion zu erreichen. Die konventionelle Gummi- und Bimssteinpolitur kann nach 20sekündiger Prophy-Jet^®-Bestrahlung entfallen.

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Summary The purpose of this in vitro investigation was to ascertain the effects of the Prophy-Jet^® air-powder abrasive system for enamel polishing after debonding. Three adhesives differing in filler content were included in this study: Concise^®, Genie^®, and Mono Lok^®. All specimens were examined by scanning electron microscopy and documented photographically at magnifications from 20 to 10 000. Surface analysis showed that using the Prophy-Jet^® exclusively is not sufficient to produce a clean and smooth enamel surface without residual adhesive after debonding and after one minute of exposure time, as might be justifiable in a clinical situation. After macroscopic conventional clean-up with scalers or rotary finishing instruments and five seconds of exposure time to the Prophy-Jet^® some occasional adhesive remnants could be located. After ten seconds of Prophy-Jet^® treatment all Mono Lok^®-adhesive was removed from the enamel surface; in the Concise^® and Genie^®-group few isolated adhesive remnants could be detected. The Prophy-Jet^® air-powder abrasive system was found to be efficient in supporting enamel polishing after debonding; but an accurate pretreatment with scalers or rotary finishing instruments is essential to achieve an extensive reduction of adhesive. Final polishing of the enamel surface with rubber wheels or prophy cup and pumice can be omitted after treatment with the Prophy-Jet^® for 20 seconds.

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Résumé Le but de ce travail était d'éxaminer à l'aide d'une étude in vitro, l'emploi du Prophy Jet^® pour le polissage de l'émail après l'arrachage des brackets. Dans l'étude on a analysé trois substances adhésives différentes: Concise^®, Genie^® et Mono Lok^®. Après avoir examiné les spécimens par le microscope électronique à balayage, on les a documentés à l'aide de photos d'un grossissement de 20 à 10 000. L'analyse de la surface montre que la seule application du Prophy Jet^® (après l'arrachage des brackets) ne suffit pas pour obtenir une surface d'émail sans substance adhésive en un temps clinique d'une minute par dent. Après prétraitement macroscopique selon la méthode conventionnelle (scaler ou instruments montés sur tour) il demeurait encore de petits restes de la substance adhésive après l'application du Prophy Jet^® pendant cinq secondes. Après une durée d'application de dix secondes, on ne pouvait pas déceler de restes de Mono Lok^®, tandis qu'il y avait sporadiquement des restes de Concise^® et Genie^®. Ces résultats indiquent, que le Prophy Jet^® est efficace pour le polissage de l'émail après l'arrachage des brackets, mais on a tout de même besoin d'un nettoyage précédent minutieux avec des instruments convenables (scaler ou instruments montés sur le tour) pour obtenir une réduction considérable de la substance adhésive. On peut renoncer au polissage conventionnel à l'aide de caoutchouc ou de la pierre ponce après l'application du Prophy Jet^® pendant 20 secondes.

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Vortrag auf der wissenschaftlichen Jahrestagung der Deutschen Gesellschaft für Kieferorthopädie 1985.     

Diacetyl-Induced Lung Disease

Diacetyl is a diketone flavouring agent that is commonly employed for buttery taste as well as other purposes. Industrial exposure to flavouring agents, particularly diacetyl, has recently been associated with bronchiolitis obliterans, a severe respiratory illness producing fibrosis and obstruction of the small airways. This has been most commonly reported in the microwave popcorn production industry, but it has occurred elsewhere. In addition to bronchiolitis obliterans, spirometry abnormalities (fixed airflow obstruction) and respiratory symptoms have been associated with exposure. A direct effect on the respiratory epithelium with the disorganised fibrotic repair appears most likely as the underlying mechanism. Current data suggest that diacetyl is the agent responsible, although it is possible that diacetyl is simply a marker for another causative agent.