Mitigation of an anthracycline-induced cardiomyopathy by pretreatment with razoxane: a quantitative morphological assessment

A quantitative evaluation of structural modifications was undertaken in the myocardium of daunorubicin (DNR)-treated and razoxane (RZ)-protected mice. BDF1 mice were injected with DNR, 15 mg/kg; a second group of mice was subjected to the same conditions but, in addition, received a pretreatment of RZ, 200 mg/kg. Representative cubes of myocardial tissue were processed for viewing with the electron microscope. Five hundred myocardial cells in each group were examined for the presence of lesions which had been categorized as early, moderate, or advanced. Contrasting the total number of demonstrable lesions in each group revealed a statistically significant reduction of 38% in abnormalities present in RZ-protected mice. By category, RZ-pretreated mice showed a mitigation in the appearance of early and moderate alterations and a striking reduction in the incidence of advanced, irreversible lesions. These results indicate that the cardiomyopathy associated with DNR administration can be ameliorated by pretreatment with RZ; this protective effect is markedly exerted by preventing the development of severe, irreversible lesions in the murine myocardium; the initial, non-transient structural alteration subsequent to DNR-exposure appears to affect the myocardial sarcoplasmic reticulum.     

On the empirical choice of the time window for restricted mean survival time

The t-year mean survival or restricted mean survival time (RMST) has been used as an appealing summary of the survival distribution within a time window [0, t]. RMST is the patient's life expectancy until time t and can be estimated nonparametrically by the area under the Kaplan-Meier curve up to t. In a comparative study, the difference or ratio of two RMSTs has been utilized to quantify the between-group-difference as a clinically interpretable alternative summary to the hazard ratio. The choice of the time window [0, t] may be prespecified at the design stage of the study based on clinical considerations. On the other hand, after the survival data have been collected, the choice of time point t could be data-dependent. The standard inferential procedures for the corresponding RMST, which is also data-dependent, ignore this subtle yet important issue. In this paper, we clarify how to make inference about a random “parameter.” Moreover, we demonstrate that under a rather mild condition on the censoring distribution, one can make inference about the RMST up to t, where t is less than or even equal to the largest follow-up time (either observed or censored) in the study. This finding reduces the subjectivity of the choice of t empirically. The proposal is illustrated with the survival data from a primary biliary cirrhosis study, and its finite sample properties are investigated via an extensive simulation study.     

Complement C7 deficiency: seven further molecular defects and their associated marker haplotypes

Seven further molecular bases of C7 deficiency are described. All these new molecular defects involve single-nucleotide events, deletions and substitutions, some of which alter splice sites, and others codons. They are distributed along the C7 gene, but predominantly towards the 3′ end. All were found in compound heterozygous individuals. The C6/C7 marker haplotypes associated with most C7 defects are tabulated. Received: 30 March 1998 / Accepted: 3 July 1998     

The survival of some soil mites at different humidities and their reaction to humidity gradients

The survival at different humidities of 10 species of soil mites in larval, nymphal and adult stages has been investigated. The immature forms are almost as resistant as mature but differences exist between species. Moisture preferences were also investigated and some form of ortho-kinesis may explain the results.

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Zusammenfassung Acht Oribatiden- und zwei Uropodiden-Arten wurden einem Feuchtigkeitsgefälle von völliger Sättigung bis zu 13% rel. Luftfeuchtigkeit ausgesetzt. Erwachsene Pelops acromios, Cepheus dentatus und Odontocephus elongatus zeigten sowohl bei 10° wie bei 20° in allen Feuchtigkeitsstufen nach drei Tagen eine 100% ige Überlebensrate. Ceratoppia bipilis, Oribata gracilipes und Euzetes seminulum wiesen bei niederer Luftfeuchtigkeit erhöhte Sterblichkeit auf und bei 13% rel. Luftfeuchtigkeit betrugen ihre Überlebensraten nach drei Tagen 75, 55 bzw. 45%. Hermannia gibba, Platynothrus peltifer, Olodiscus integra und Cilliba cassidea zeigten unter 55% rel. Luftfeuchtigkeit alle einen plötzlichen Abfall der Überlebensrate und am Ende von drei Tagen blieben nur wenige Individuen am Leben. Die Fähigkeit der larvalen und Nymphenstadien, erniedrigte Luftfeuchtigkeit zu ertragen, war im allgemeinen etwas geringer als bei den Adulten, doch zeigten die Arten untereinander die gleiche relative Resistenz wie bei den Erwachsenen. In einer alternativen Wahlkammer, die ein Feuchtigkeitsgefälle aufwies, bevorzugten alle Arten die feuchtere Hälfte. Nur wenn die Wahl zwischen 94% und 100% rel. Luftfeuchtigkeit geboten wurde, bevorzugten P. acromios, C. dentatus und O. elongatus die geringere Feuchte. Die Ergebnisse weisen darauf hin, daß eine Form von Orthokinese vorliegt und noch kein Unterschied in der Anzahl der Individuen beobachtet wurde, die sich bei gleichmäßiger Feuchtigkeit von 10, 47 und 100% rel. Luftfeuchtigkeit bewegten. Im Vergleich zwischen feuchten und trockenen Bedingungen besteht kein wahr nehmbarer Sensibilitätsunterschied.

     

Role of complement components on cells and in cell interactions.

The complement system, though complex, is relatively easy to study both in terms of its reaction pathways, its distribution and its genetics. There is reason to believe that the complement system is involved in cell surface events and interactions at a variety of levels and we may hope that the knowledge of the system in the blood plasma will provide relatively easy insights into the more difficult areas with cells.