Neurovirulence of Cryptococcus neoformans determined by time course of capsule accumulation and total volume of capsule in the brain.

Cryptococcal meningitis remains a significant opportunistic infection in HIV-infected individuals worldwide, despite availability of antiretroviral therapies in developed nations. Current therapy with amphotericin B is difficult to administer and only partially effective. Mechanisms of cryptococcal neuropathogenesis are still not clearly defined. In the present study, we used a C57Bl/6 mouse model with intravenous inoculation of three isogenic strains of Cryptococcus neoformans: H99, Cap59, and Pkr1-33. These strains differ in their capsule production and are normocapsular, hypocapsular, and hypercapsular, respectively. We studied the role of capsule in the morbidity and mortality of our host animal. Surprisingly, we found that the hypercapsular strain was least virulent while the strains that produced less capsule were more virulent and had higher concentrations of organism in the brain. These results suggest that neurovirulence is related to total capsule volume and rate of capsule accumulation in the brain, rather than the amount of capsule produced per organism. Therapies which decrease central nervous system dissemination and inhibit replication rates in the brain may be more effective than therapies which target capsule production.

Iontophoresis: a needle-free, electrical system of local anesthesia delivery for pediatric surgical office procedures.

BACKGROUND/PURPOSE: Delivery of local anesthesia for surgical office procedures for pediatric patients can be difficult. Injections are painful and often lead to patient anxiety, and topical anesthetics frequently provide incomplete anesthesia. The authors prospectively studied the efficacy of iontophoresis, a needle-free technique in which positively charged lidocaine and epinephrine molecules are drawn into the tissue by an electrical current as an anesthetic for pediatric surgical office procedures. METHODS: Children undergoing an office procedure were offered local anesthesia via iontophoresis. Prospectively collected data included patient characteristics, procedure, iontophoresis dose and time, need for additional injected anesthetic, pain during the procedure as determined by a 0 to 5 faces scale, and complications. A satisfaction questionnaire was completed at the follow-up visit or by telephone. RESULTS: Over an 8-month period, 34 patients with a mean age of 6.8 years (range, 3 months to 15 years) underwent 38 office procedures with anesthesia supplied through iontophoresis. Skin lesion excision (n = 14) and abscess drainage (n = 12) were the most common procedures. Seven patients required unplanned injected anesthetic. A small, superficial burn was the only complication. Sixty percent of patients and 84% of parents rated pain as 0 to 2 (zero to mild). Overall, 88% were satisfied with the anesthetic. CONCLUSION: Iontophoresis appears to be an effective and safe alternative method of local anesthesia delivery for pediatric surgical office procedures.

Initial experience using the Food and Drug administration guidelines for emergency research without consent.

Beginning November 6, 1996, Food and Drug Administration regulation 21 CFR 50.24 has allowed research without consent in limited circumstances while requiring additional patient protection in the form of community consultation and disclosure. We report our experience in complying with these regulations in Multicenter Vest CPR protocol, the first investigational device study done under this new ruling. We found uncertainty in inter-pretation of the requirements for community consultation. The acceptance of research without consent varied among the parties exposed to this protocol, but neither physicians nor the lay public expressed major reservations. The consultation process was time-consuming, demanding, and relatively costly. Further clarification of the community consultation standard and additional dialogue on this important topic will help to foster additional research in cardiopulmonary resuscitation.