Idiopathic chondrolysis of the ankle.

A 21-year-old West Point cadet presented to our institution with a history of chronic left lateral ankle instability. The initial injury occurred 5 years earlier. Physical examination results and stress radiographs were consistent with lateral instability. The patient underwent an ankle arthroscopy and lateral ankle ligament reconstruction. Arthroscopic findings included moderate synovitis, grade II anterolateral chondrosis, and an anterior talar osteophyte. The patient had an uneventful postoperative course and returned to activity. Eleven months after surgery he presented with increased left ankle pain. On physical examination he had a stable ankle, but radiographs revealed marked loss of ankle joint space. Significant diffuse fraying and thinning of the articular cartilage noted on repeat arthroscopy were consistent with chondrolysis.

Restoration of spermatogenesis in dibromochloropropane (DBCP)-treated rats by hormone suppression.

The exposure of men to the nematocide dibromochloropropane (DBCP) has caused prolonged oligo- and azoospermia, which occasionally reverses spontaneously. We recently demonstrated that in testes of rats treated with a dose of DBCP sufficient to reduce the percentage of tubules producing differentiating germ cells (tubule differentiation index, TDI) to 20%, the tubules lacking differentiating cells contained type A spermatogonia. To determine whether these type A spermatogonia could be stimulated to differentiate, as had been demonstrated previously in other models of toxicant-induced sterility, we suppressed intratesticular testosterone and serum follicle stimulating hormone (FSH) levels with the GnRH agonist Lupron (leuprolide). When the GnRH agonist was given for 10 weeks starting immediately after DBCP exposure, the TDI was maintained at 94%. Even when GnRH-agonist treatment was stopped at week 10, the TDI remained between 65 and 80% 10 weeks later. Late spermatid counts averaged 10 x 10(6) per testis for the GnRH-agonist-treated rats at week 20 compared with 1.7 x 10(6) per testis in rats treated with only DBCP. To determine whether spermatogonial differentiation could be stimulated after the TDI had declined to below 30%, we initiated GnRH-agonist treatment 6 weeks after DBCP exposure. The GnRH treatment increased the TDI to 53% at week 16. These results indicate that, if the same principles apply to humans, suppression of testosterone may be applied to restore spermatogenesis in men rendered azoospermic by DBCP or other reproductive toxicants.

Dibromochloropropane inhibits spermatogonial development in rats.

Exposure to the nematocide dibromochloropropane (DBCP) has caused prolonged oligo- and azoospermia in men. There are questions regarding the cellular targets resulting in this effect. In this study we characterized an animal model, in which four daily injections of DBCP produced prolonged oligospermia in LBNF(1) rats without any indication of recovery. Between 6 and 20 weeks after DBCP treatment, 70% of seminiferous tubules showed an epithelium with Sertoli cells but no differentiating germ cells. About 20% of tubules contained differentiating germ cells and 10% showed occlusion or major morphologic alterations to Sertoli cells. Since gonadotropin levels and intratesticular testosterone (ITT) concentrations were elevated in the DBCP-treated rats, the failure of spermatogonial development could not have been a result of lack of these hormones. The tubules without differentiating germ cells contained actively proliferating and dividing type A spermatogonia, which underwent apoptosis instead of differentiation. Thus, the target for the damaging effect appears not to be the killing of stem spermatogonia, but the loss of their ability to undergo differentiation. The presence of type A spermatogonia in the atrophic tubules indicates the potential for intervention to restore spermatogenesis.

Inhibition of recovery of spermatogenesis in irradiated rats by different androgens.

We previously showed that exogenous testosterone (T) inhibited GnRH-antagonist-stimulated spermatogenic recovery in irradiated rats through an androgen-receptor-mediated action. In the present study, we tested whether the inhibition is attributable to T, a specific androgenic metabolite of T, or a general property of androgens in this system. In addition, we also tested whether estradiol-17beta (E2), a metabolite of T, is similarly inhibitory. Rats irradiated with 5 Gy were treated with a GnRH antagonist during wk 3-7. Neither irradiation nor GnRH-antagonist treatment produced biologically significant changes in the relative intratesticular levels of several androgenic metabolites. Next, groups of rats, irradiated and treated with GnRH antagonist as above, were given various doses of one of the following androgens: T, 5alpha-dihydrotestosterone, 7alpha-methyl-19-nortestosterone, methyltrienolone, or E2. The percentage of tubules showing differentiation (tubule differentiation index) was increased to 68% by the GnRH antagonist, from a value of 0.1% in irradiated-only rats at 13 wk after irradiation. All of the added androgens inhibited spermatogenic recovery, lowering the tubule differentiation index to between 0.4-36%, but no inhibition was observed with the addition of E2. Of all the androgen treatments tested, T (given as daily injections of T propionate) minimally inhibited spermatogenic recovery while maintaining androgen-responsive tissue weights, and might be most useful in clinical studies. Hormonal measurements in androgen-treated rats were most consistent with the androgen inhibition of spermatogenic recovery in irradiated rats being a combined result of a direct inhibitory effect of all androgens on the testis and an indirect effect through the pituitary by raising levels of FSH, which seems to add to the inhibition of spermatogenic recovery.