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.     

Decreased P-glycoprotein expression in multidrug-sensitive and -resistant human myeloma cells induced by the cytokine leukoregulin.

Modulation of the expression of P-glycoprotein, a plasma membrane protein associated with multidrug resistance, was examined in drug-sensitive and drug-resistant tumor cells treated with leukoregulin, a M(r) 50,000 cytokine from human lymphocytes that rapidly permeabilizes the plasma membrane of many tumor cells facilitating the uptake of doxorubicin and other tumor-inhibitory antibiotics. P-glycoprotein expression was measured flow cytometrically by the binding of C219 or MRK16 monoclonal antibody to multidrug-sensitive human K562 erythroleukemia and 8226/S myeloma cells, compared to multidrug-resistant 8226/DOX40 myeloma cells. Cells were treated for up to 2 h with up to 80 units of leukoregulin/ml or one of a variety of unrelated cytokines including interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, colony-stimulating factor, macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, gamma-interferon, alpha-interferon, epidermal growth factor, platelet-derived growth factor AA, platelet-derived growth factor BB, insulin-like growth factor I, insulin-like growth factor II, fibroblast growth factor, or transforming growth factor beta. Leukoregulin caused a concentration-dependent decrease in P-glycoprotein expression; however, P-glycoprotein expression was unaffected by the other cytokines (< 12% decrease in expression). Leukoregulin-induced membrane permeabilization, determined flow cytometrically by intracellular fluorescein efflux, and decreased P-glycoprotein expression occurred simultaneously within 15 min in drug-sensitive and -resistant cells. Enhanced doxorubicin uptake, measured flow cytometrically by doxorubicin influx, was also present within 15 min. Leukoregulin enhancement of doxorubicin uptake and increased membrane permeability varied directly with the decrease in P-glycoprotein expression. Leukoregulin in combination with doxorubicin enhanced the inhibition of cell proliferation in 8226/DOX40 multidrug-resistant cells over expressing P-glycoprotein. In contrast, combined treatment of HL-60/MX2 multidrug-resistant human promyelocytic leukemia cells that do not overexpress P-glycoprotein in association with their multidrug resistance resulted in no greater growth inhibition than observed with HL-60/MX2 cells treated with doxorubicin alone. This is the first demonstration that a naturally occurring macromolecule with anticancer activities can modulate the expression of P-glycoprotein concomitant with enhanced drug uptake and inhibition of cell proliferation.     

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.      

Pharmacokinetics and pharmacodynamics of anticancer agents: contributions to the therapy of childhood cancer

Strategies for treating pediatric malignancies have not only been successful (i.e., curative) for several disseminated childhood cancers, they have also served as paradigms for the therapy of many adult cancers. Initial strategies included combined treatment modalities (chemotherapy, surgery, radiotherapy) and combinations of different pharmacologic classes of anticancer drugs given in the appropriate schedules. Despite the currently successful therapy for some malignancies (e.g., 70% 4-year disease-free survival in acute lymphocytic leukemia), many children die without known reason. Recent advances in the clinical pharmacology of anticancer drugs have identified relationships between dose intensity and response (efficacy, toxicity). Traditional methods of measuring dose intensity (prescribed dose) have evolved to more sophisticated approaches in maximizing the intensity of treatment, with good response rates. Other methods of optimizing chemotherapy for individual patients include bone marrow support procedures and therapy with biologic response modifiers. Relatively few clinically useful new anticancer drugs have been discovered in the past several years. Fortunately, the potential to improve therapy with currently available agents has come about through enhanced knowledge of the biochemical and clinical pharmacology of anticancer drugs and biologic response modifiers, as well as improved understanding drug resistance biology.     

Titration of duration discrimination in behavioral pharmacology and toxicology

This study investigated a discrete-trial, titration duration discrimination procedure in behavioral pharmacology. Pentobarbital and d-amphetamine, measured with this procedure, selectively affected discrimination more than response tendencies. Pentobarbital also tended to affect selectively discrimination of longer durations, whereas d-amphetamine did not. Further experiments showed that (1) other algorithms for modulating stimulus duration are useful in behavioral pharmacology and toxicology, (2) threshold estimates are similar with the method of constant stimuli and the method of titration, and (3) this titration procedure permits the separate examination of drug effects upon discrimination and upon response tendencies; the fixed-interval procedure does not. Baseline variability was an important correlate of drug effects in that the endpoints with more variable baselines were also more sensitive to drugs.