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We studied the fluctuations in phenytoin (PHT) levels during ovulatory and menstrual phases of the cycle, in eight patients with catamenial epilepsy and in eight age-matched controls. Pharmacokinetic studies of PHT were done in five patients with catamenial epilepsy. The difference in PHT levels during menstrual and ovulatory phase in catamenial group was 3.44 +/- 3.25 micrograms/ml as compared with 0.91 +/- 2.03 micrograms/ml in controls. The mean fall during menstrual phase was significant (p less than 0.05) in the catamenial group. There was also rapid though statistically nonsignificant clearance of PHT during menses as compared with the ovulatory period. It is presumed that the fall in plasma PHT levels during menses, though still within therapeutic range, may be responsible for catamenial exacerbation of epilepsy.

SUMMARYWe have prepared human recombinant antibody molecules against the glycoprotein antigen of the rabies virus (GPRV) based on the single chain variable fragment (scFv) format. Anti-GPRV scFvs were selected from a human synthetic scFv phage display library with a repertoire of approximately 10 9 specificities. After three rounds of selection against the PV11 strain of the virus, 40% of the clones tested recognized the rabies antigen. Of the 20 positive clones that were sequenced, five distinct sequences were identified. These distinct scFvs were cloned into a mammalian expression vector carrying the human IgG1 Fc region. The specificity of the resulting scFv-Fc molecules for GPRV was established by ELISA, dot blot and western blot analyses and membrane immunofluorescence. Two of the scFv-Fc fusion proteins neutralized the PV11 strain in a standard in vivo neutralization assay where the virus was incubated with the scFv-Fc molecules before intracranial inoculation in mice. These anti-GPRV scFv-Fc molecules have the potential to be used as an alternative to the presently available HRIG, for use in post-exposure preventive treatment.

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