Indomethacin distribution in acute pharmacological response among rats

A detailed examination of quantitative relationships of pharmacological action with plasma and tissue concentrations of indomethacin has been undertaken in the rat, after single oral administration of two sustained release preparations. In this study, drug was assayed by high performance liquid chromatography, whereas antiinflammatory response was assessed through the carrageenin-induced edema test. Significant linear correlations (p less than 0.001) were found between logarithmically transformed percent inhibition of edema and logarithmically transformed plasma, as well as tissue levels of indomethacin. However, the lack of significance for partial correlation regarding tissue concentration, contrary to plasma concentration, suggests that pharmacological response is more closely related to the latter, indicating that antidematous effect is mediated via the circulating drug rather than a local action in target tissues. This assumption is further discussed from the equivalence point of view. The relevance of this type of study in the case of topical administration of indomethacin is addressed as well. Taking into account the predictive value of the rat paw edema test for clinical efficacy, relationships similar to those observed are to be expected in man. The high correlation existing between plasma concentration of indomethacin and its pharmacological effect justifies the development and use of sustained release preparations in order to improve the outcome of treatment with this nonsteroidal antiinflammatory drug.     

Narrowband UVB therapy for vitiligo: does the repigmentation last?

BACKGROUND: Since 1997, a number of trials have shown promising results in treating generalized vitiligo with narrowband ultraviolet B (UVB) both in adults and children. However, there is little knowledge concerning the duration and permanency of the treatment-induced repigmentation. OBJECTIVE: Our main objective was to perform a follow-up trial of successfully treated patients receiving narrowband UVB for generalized vitiligo. METHODS: We have investigated to what degree the treatment-induced repigmentation remains stable for up to 2 years post-treatment. We performed an initial open trial including 31 patients with generalized vitiligo. They received narrowband UVB thrice weekly for up to 12 months. Patients experiencing > 75% repigmentation were defined responders and were included in the follow-up trial. Responders were followed every 6 months for up to 2 years after cessation of treatment. We observed the pigmentation status and registered any changes indicating loss of pigmentation and relapse. RESULTS: Eleven of the 31 treated patients were included in the follow-up trial. Six patients had relapse and five patients had stable response 24 months after cessation of treatment. Four out of six relapses were within 6 months post-treatment. CONCLUSION: In our study population of 31 patients with generalized vitiligo, five patients (16%) experienced > 75% stable repigmentation 2 years after cessation of a treatment programme of up to 1 years narrowband UVB therapy.     

An evaluation of CA 549, a circulating marker of breast cancer using a procedure for comparison with CA 15.3.

A serum assay of CA 549 (Hybri-BREScan CA 549 degrees, Hybritech), a new tumor marker, was performed in 129 patients with breast cancer and 35 healthy women, in parallel with CA 15.3 (ELSA-CA 15.3 degrees, CIS Biointernational). Comparing 95 women with primary breast carcinoma and 35 controls, Relative (or Receiver) Operating Characteristic (ROC) analysis revealed that the Area Under ROC Curve (AUC) of CA 15.3 was significantly higher than that of CA 549, indicating that, for our population, the first marker was more effective. Parallel and series analyses were also performed using ROC AUC and revealed that the combination of these two tests did not give more information than the CA 15.3 test alone; however, they did not in any way constitute diagnostic tools. In our experience, the best field of application for CA 549 seems to be the therapeutic monitoring and early detection of breast cancer recurrences. However, further investigations on a larger scale are necessary to assess more precisely the place of CA 549 in following the clinical course of breast cancer patients.     

Ongoing pregnancies after intracytoplasmic injection using cryopreserved testicular spermatozoa

We report two clinical pregnancies occurring after intracytoplasmic sperm injection (ICSI) using cryopreserved spermatozoa obtained from testicular biopsy, made in two different infertility situations in our clinic. The first patient showed a secretory azoospermia associated with elevated serum follicular stimulating hormone (FSH) level and spermiogenesis maturation arrest. The second patient was affected by azoospermia resulting from bilateral epididymal obstruction. Spermatozoa present in the wet preparation of testicular biopsy made on the day of scrotal exploration were cryopreserved within the testicular tissue for both men. Intracytoplasmic injections were performed at a later date, using spermatozoa prepared from frozen-thawed tissues. In each case, three embryos were obtained and transferred in utero. The transfers resulted in a twin pregnancy for the first case, and in a singleton pregnancy for the second. Living foetuses were seen in the ultrasound scan at the 7th week and both pregnancies are proceeding to date beyond 30 weeks without complications.