To determine the safety and immunogenicity of an inactivated hepatitis A vaccine, 56 healthy adult volunteers were randomly assigned to receive an intramuscular injection of 6.3, 12.5 or 25 ng of ...inactivated hepatitis A vaccine or placebo at 0, 2 or 4, and 24 weeks. Adverse reactions occurred with similar frequency in vaccine and placebo recipients and consisted primarily of pain or tenderness at the injection site. By 4 weeks after a single 6.3, 12.5 or 25 ng injection, seven, nine and ten out of ten vaccinees, respectively, had antibody detectable by a HAV AB assay modified to increase its sensitivity tenfold. All vaccinees had antibodies detectable by this assay within 2 weeks of their second inoculation. Geometric mean antibody levels increased with higher doses of vaccine (p = 0.05). Neutralizing antibody was detected within 4 weeks of a single inoculation in all vaccinees. Neutralizing antibody was detected after the third inoculation at dilutions of greater than or equal to 1:2048 in all 12.5 and 25 ng vaccinees. All 19 vaccinees tested at 24 months still had HAV antibodies detectable by a modified HAV AB assay. This inactivated hepatitis A vaccine appears to be well tolerated and immunogenic at doses of 6.3-25 ng. The choice of dose and vaccination schedule may depend on the rapidity with which seroconversion is desired.
The class I gene products of the Syrian hamster major histocompatibility complex are unique in that they lack functionally detectable polymorphism. Mouse cDNA and hamster genomic probes were used to ...analyze the hamster class I gene family using genomic Southern hybridization. These studies revealed that the hamster possesses a complex class I multigene family and that it shares extensive sequence homology with the corresponding mouse sequences. Unlike the mouse, however, the Syrian hamster demonstrates only limited restriction endonuclease polymorphism in these genes. These results suggest that the lack of detectable polymorphism in this species is directly related to limited DNA polymorphism. The data presented here support the hypothesis that this species has undergone an evolutionary bottleneck, i.e., that all surviving members of the species arose from a limited number of progenitors.
The Gynecologic Oncology Group (GOG) conducted a Phase II trial of CHIP, cis-dichloro-trans-dihydroxy-bis-(isopropylamine)-platinum IV, in patients with measurable advanced squamous cell carcinoma of ...the cervix. No prior therapy with cytotoxic drugs was permitted in patients entered into this trial. All patients had a GOG performance status of 2 or better. CHIP at a starting dose of 230 mg/m2 was administered as a 30-minute IV infusion. Dose escalation was permitted to a maximum of 300 mg/m2. Treatments were repeated every four weeks until disease progressed or until toxicity prohibited further therapy. Thirty-six evaluable patients were entered between January and July, 1984. Of these, 34 were evaluable for response. Four complete and three partial responses were observed (response rate 20.6%). No neurotoxicity was noted and only mild and reversible nephrotoxicity was reported. Grade 3 gastrointestinal toxicity was reported in twenty patients (56%). Dose-limiting toxicity was myelosuppression. CHIP is an active agent against squamous cell carcinoma of the cervix and appears to be less neurotoxic and nephrotoxic than cisplatin. Gastrointestinal toxicity was moderate and appears equal to that seen with cisplatin at a dose of 50 mg/m2 given as a rapid IV infusion and more toxic than an equivalent dose of cisplatin administered over 24 hours. Randomized studies comparing CHIP and cisplatin are indicated to better define the relative therapeutic indices of these two compounds in the treatment of advanced squamous carcinoma of the cervix.
