Long-term weekly treatment with fluconazole can reduce the rate of recurrence of symptomatic vulvovaginal candidiasis. However, a long-term cure remains difficult to achieve.

I.

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GlaxoSmithKline Biologicals SA.

Degenerative lesions characterized by osteochondrophyte spur formation and cartilage degeneration were induced by partial meniscectomy in the rabbit knee. Cartilage degenerative lesions included ulceration, fissure and cyst formation, and diminished concentration of matrix proteinpolysaccharide. Proliferation of chondrocytes represented efforts at repair. Osteophytes increased in size with time. Changes resembled certain components of degenerative joint disease. The partial meniscectorny animal may be useful in studies of osteoarthritis pathogenesis, pathology and treatment.Degenerative joint changes frequently follow meniscus injury in the human (1,2). In the present study degenerative lesions characterized by osteochondrophyte spur formation and cartilage degeneration were induced by partial meniscectomy in the rabbit knee. Since the pathologic changes observed resemble certain components of degenerative joint disease, the partial meniscectomy animal may be useful in studies of osteoarthritis pathogenesis, pathology and treatment. MATERIALS AND METHODSNew Zealand white rabbits were divided into three groups for study. The animals in the three groups were of relatively similar characteristics with respect to range of weight and to average and median weights (Table 1). Group 1, 82 rabbits, comprised the experimental meniscus surgery model. The rabbits were anesthetized with IV sodium pentothal (Diabutalm, E.L. Squibb and Sons, New York, NY) after which, under sterile surgical conditions, an anteromedial incision was made in the right knee. The soft tissue and retinaculum were incised and reflected medially and laterally. The joint capsule was then incised and the medial compartment of the knee exposed. Using iris scissors, the peripheral attachment of the anterior one-half of the medial meniscus was released and the anterior one-third of the meniscus excised (Figure 1). The capsule and medial retinaculum were closed with three 5-0 catgut sutures and the skin closed with 4-0 silk suture. The operated extremity was placed in a long-leg plaster cylinder cast with the knee and ankle joints maintained at angles of approximately 9W. After 1 week the cast and skin sutures were removed and the animals allowed to move freely in their cages. Sacrifice using intravenous injection of Diabutal was carried out at periodic intervals of 2, 5, 8 and 12 weeks postoperatively ( Table 1). The largest number of animals in the series comprised those sacrificed at 12 weeks, since this became the standard model being used in ongoing experimental studies. The operated knees were carefully dissected and examined for gross changes, Particular note was made of the presence of osteophyte-like spur formation, pitting and ulcerative erosions. Severity of spur formation was graded as follows: mild-spur present and less than 2 mm in maximal width; moderate-spur 2 mm in maximal width: and severespur exceeding 2 mm in maximal width. Ulcers were graded

The high dose+adjuvant (100 μg antigen+AlOH) formulation administered at 0-7-30 days elicited the best immune response profile, including functional antibody responses, through Day 180 and was selected for use in subsequent clinical trials.

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