In vascularized organ transplants, gender mismatches have higher rates of immunological rejection. We investigated the influence of gender incompatibility, including H‐Y incompatibility, on corneal transplant graft rejection and failure. Patients were included who had undergone a first corneal transplant for keratoconus (KC), Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK), infection and other indications. A Cox regression model was fitted for each indication to determine factors affecting graft failure and rejection at 5 years. The impact of gender, including H‐Y, matching was analyzed after accounting for other factors, including known risk factors. Of 18 171 patients, 4314 had undergone a transplant for FED, 4783 for KC, 3669 for PBK, 1903 for infection and 3502 for other disorders. H‐Y mismatched (male [M]→female [F]) corneas were at greater risk of graft failure or rejection. For FED, F→F were 40% less likely to fail (p < 0.0001) and 30% less likely to reject (p = 0.01); M→M were 20% less likely to fail (p = 0.04) and 30% less likely to reject (p = 0.01). For KC, M→M matched corneas were 30% less likely to fail (p = 0.05) and 20% less likely to reject (p = 0.01) compared with H‐Y mismatches. H‐Y antigen mismatched (M→F) patients were at greater risk of rejection or graft failure.

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SummaryThe comparative cytopathic effects of a keratitis and an environmental isolate of Acanthamoeba were studied on confluent monolayers of human and rabbit corneal cells grown in culture. The presence of cells in culture induced excystment of amoe bae to the active trophozoite form. Total destruction of cell monolayers was observed to be similar for both isolates, and dependent on incubation time and amoebic con centration. The relevance of these findings to human and experimental Acantha moeba keratitis is discussed.Acanthamoeba is a genus of free-living amoe bae which is ubiquitous in air, soil and aquatic environments. The active trophozoite form becomes a resilient cyst in unfavourable environmental conditions. Acanthamoeba is a cause of chronic granulomatous encephalitis, which occurs in immunocompromised hosts and is fatal. 1 Certain species cause chronic stromal keratitis, particularly in contact lens wearers whose lens solutions become contam inated by the amoeba. 2 The amoebae flourish in the corneal stroma, and a severe polymor phonuclear inflammatory response and cor neal thinning is observed in both human3 and experimental4 keratitis.In vitro studies of Acanthamoeba virulence have been performed on VERO cells5•6•7 a cell line derived from monkey kidney, or SIRC cells ,8 derived from rabbit cornea. These stud ies equated the speed with which the mamma lian cells were destroyed to virulence, and to pathogenicity in laboratory animals. 6 Isolated rabbit corneas, used as an in vitro model for amoebic infection, demonstrated a similar destructive effect by known pathogenic and non-pathogenic strains of amoebae.8Two questions have prompted this study.The first was raised by Garner, who ques tioned whether the corneal thinning is caused by the inflammatory response or the amoebae themselves.3 Can Acanthamoeba feed on cor neal cells? The second relates to the marked site-specificity of clinical Acanthamoeba infection: is corneal tissue unduly susceptible to amoebic infection? To answer these questions we studied the interaction of Acanthamoeba and cell cul tures. We first investigated whether Acantha moeba excysts in the presence of cultured cells, and whether a cytopathic effect (CPE) results. We then conducted a comparative investigation of the effect of amoebic tropho zoites on primary cultures of human and rab bit corneal cells, and on 3T3 alpha cells, a mouse fibroblast cell line. We contrasted the CPEs of Acanthamoeba spp. on these cells, and compared an environmental isolate with an isolate from an infected cornea. Materials and Methods Preparation of AcanthamoebaTwo strains of Acanthamoeba were used in these studies: an isolate from an infected cor nea, A. polyphaga (Davies), and a soil isolate

Context: In hereditary cancer syndrome families with an identified cancer associated mutation, mutation testing changes the carrier risk status of the tested person and may change the carrier risk status of relatives. Objective: This study aimed to describe the change in the distribution of carrier risk status resulting from testing in hereditary breast-ovarian cancer (HBOC) and hereditary non-polyposis colorectal cancer (HNPCC) families. Design: This was an observational cohort study. Patients: The cohort included members of 75 HBOC and 47 HNPCC families. Of the 10 910 cohort members, 1408 were tested for a mutation and learned their test results. Outcome measure: Carrier risk for all cohort members was assessed before and after mutation testing. Results: There was a change in carrier risk status in 2906 subjects after testing of 1408 family members. The most common type of carrier risk change, from at risk to non-carrier status, accounted for 77% of the risk changes; 12% were a change to known carrier status from a lower risk. Sixty percent of persons with a carrier risk status change were not themselves tested; their risk status changed because of a relative's test result. Conclusions: Carrier risk status changes from uncertainty to certainty (that is, to carrier or to non-carrier) account for 89% of risk changes resulting from testing. These risk changes affect cancer prevention recommendations, most commonly reducing their burden. Current practices do not ensure that untested family members are informed about changes in their carrier risk status which result from mutation testing of their relatives.