Institutionally chartered Data and Safety Monitoring Boards: structured approaches to assuring participant safety in clinical research.

Data and Safety Monitoring Boards (DSMBs) derived from the need to monitor large federally funded multi-center clinical trials and evolved to include commercial and other large and complex trials. Eventually, academic health centers also created institutionally focused trial monitoring mechanisms. The basic general principles that define traditional DSMBs extend to the institutional level.

: Role and responsibilities of the independent safety officer.

Every research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk.

Improvement of postherpetic neuralgia after treatment with intravenous acyclovir followed by oral valacyclovir.

Background: Postherpetic neuralgia (PHN) is a complication of shingles (herpes zoster), a painful rash due to varicella-zoster virus reactivation. Studies of patients with PHN and zoster sine herpete (radicular pain without rash) support the notion that low-grade viral ganglionitis contributes to pain. If chronic pain reflects active infection, then antiviral therapy may help patients with PHN.

Oligoclonal immunoglobulins in cerebrospinal fluid during varicella zoster virus (VZV) vasculopathy are directed against VZV.

Limited analyses of cerebrospinal fluid from patients with central nervous system infections have shown that the oligoclonal IgG is antibody directed against the agent that causes disease. Using a new method involving binding of IgG to beads coated with lysates prepared from candidate infectious antigens, we showed that the oligoclonal IgG in cerebrospinal fluid of a patient with chronic varicella zoster virus vasculopathy is directed against the causative virus. This approach holds promise in identifying and purifying the relevant oligoclonal IgGs in inflammatory central nervous system diseases of unknown cause.

Evaluation of cooperative interactions between substructures of iso-1-cytochrome c using double mutant cycles.

A double mutant cycle has been used to evaluate interaction energies between the global stabilizer mutation asparagine 52 --> isoleucine (N52I) in iso-1-cytochrome c and mutations producing single surface histidines at positions 26, 33, 39, 54, 73, 89, and 100. These histidine mutation sites are distributed through the four cooperative folding units of cytochrome c. The double mutant cycle starts with the iso-1-cytochrome c variant AcTM, a variant with no surface histidines and with asparagine at position 52.