Ninety military patients with cutaneous leishmaniasis in Colombia were randomly allocated to 3 treatment regimens of parenteral aminosidine sulphate: (i) 12 mg aminosidine base/kg/d for 7 d, (ii) 12 mg/kg/d for 14 d, and (iii) 18 mg/kg/d for 14 d. With the 89 evaluable patients, the cure rates 12 months after the end of treatment were 10%, 45%, and 50%, respectively. Fifty-eight of the 66 patients who were not cured had lesions that enlarged or were unchanged by 1.5 months after treatment follow up. The other 8 patients had lesions that relapsed between 3 and 12 months after therapy. Even in group (iii) the cure rate was inferior to that (> 90%) with antimony or pentamidine previously reported in this patient population. This study indicates that parenteral aminosidine alone is less likely to be successful in the treatment of cutaneous lesihmaniasis than visceral leishmaniasis, for which a 74% cure rate has been reported. Further trials might consider the combination of aminosidine with other antileishmanial drugs.

Adolescent↗

PubMedDate not supplied

Safety and immunogenicity of a killed Leishmania (L.) amazonensis vaccine against cutaneous leishmaniasis in Colombia: a randomized controlled trial.

The safety and immunogenicity of an intramuscular (i.m.) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-blind trial in Colombia. There were 4 vaccination groups: i.m. vaccine, i.m. placebo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the groups. Montenegro skin-test conversion was achieved by 86.4% and 90% of the i.m. vaccine group and by 25% and 5% of the i.m. placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigen lymphocyte proliferation indexes was observed after i.m. vaccine immunization, but not after i.m. placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma but not IL-10 were observed 1 year after vaccination in the i.m. vaccine group compared to the i.m. placebo group. The good safety profile and evidence of Th1 immune reactions due to i.m. vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the i.m. vaccine should be initiated.

Adjuvants, Immunologic↗

PubMedDate not supplied

Hemodynamic evaluation of the female sexual arousal response in an animal model.

The goal of this study was to assess the utility of existing and new techniques for characterizing and measuring hemodynamic changes in the vagina and clitoris in response to pelvic nerve stimulation (PNS) in an animal model. Using female New Zealand White rabbits, we measured the following parameters before, during, and after PNS at 4, 16, and 32 hertz (Hz): clitoral hemoglobin (Hb) content by laser oximetry, clitoral blood flow by laser Doppler flowmetry, vaginal luminal pressure of upper and lower segments, and clitoral intracavernosal pressure. Clitoral tissue concentrations of total and oxygenated hemoglobin (oxy-Hb) increased in a frequency-dependent manner while deoxygenated hemoglobin (deoxy-Hb) concentration decreased. The duration of the responses at 16 and 32 Hz were significantly greater than at 4 Hz. Clitoral blood flow increased significantly only at 32 Hz with a prolonged response duration, relative to 4 Hz. PNS caused vaginal luminal pressure changes that were highly variable, but qualitatively different, between the upper and lower regions. Clitoral intracavernosal pressure did not change significantly in response to PNS. Measurement of changes in tissue Hb content by the novel technique of laser oximetry provides a direct assessment of blood flow in a noninvasive manner and may prove to be a powerful tool in evaluating hemodynamic aspects of the female genital sexual response.

Animals↗

PubMedDate not supplied

A new non-pharmacological vacuum therapy for female sexual dysfunction.

Although Female Sexual Dysfunction (FSD) affects 40% of American women, there is no FDA-approved pharmaceutical therapy. The EROS-CTD (Clitoral Therapy Device, UroMetrics, Inc., St. Paul, MN) treatment is the first FDA cleared-to-market therapy for FSD. Clitoral engorgement is believed to play an important role in female sexual arousal and overall sexual satisfaction. The EROS-CTD is a small, battery-powered device designed to enhance clitoral engorgement, increase blood flow to the clitoris, and ultimately improve arousal in women with FSD. The objective of this study was to assess the effectiveness of the EROS-CTD on sexual arousal (genital sensation, vaginal lubrication, ability to reach orgasm, and sexual satisfaction) in normal volunteers and women with FSD.

Adult↗

PubMedDate not supplied

The compliance and science of Blend Uniformity Analysis.

According to 21CFR section 211.110(a) pharmaceutical manufacturers are legally required to demonstrate the adequacy of their mixing operations. The CFR, however, is intentionally silent on how this should be accomplished. The situation changed dramatically in 1993 as a consequence of The US vs. Barr Laboratories when Judge Alfred Wolin ruled for the government that the appropriate sample size for Blend Uniformity Analysis (BUA) is, at most, three times the weight of the final dosage unit. This ruling defined the Current Good Manufacturing Practices (cGMPs) for BUA in greater detail than is specified in 21CFR section 211.110(a). It also established a precedent that has been the focus of an almost decade long controversy between pharmaceutical manufacturers and the FDA. At the heart of the matter is the inability of current sampling technology to consistently and reliably provide small representative samples from significantly larger static powder blends. The sample thief is the state-of-the-art powder sampling technology used by the pharmaceutical industry today for purposes of BUA. Unfortunately, sample thieves are intrusive devices that are prone to sampling error. Sampling error can lead to powder samples that are not representative of the bulk blend from which they were collected. In general, sampling error increases as the concentration of the drug substance and the size of the sample decrease. Since Judge Wolin's ruling, sampling error has made it difficult, if not impossible, to validate the manufacturing processes for some acceptably uniform pharmaceutical products. This article reviews the compliance history of BUA as well as the associated scientific literature.

Chemistry, Pharmaceutical↗