Posttransplantation lymphoproliferative disorder (PTLD) is an uncommon but often fatal complication of solid organ transplantation that occurs in approximately 3% of patients. To determine the relative importance and relationship of potential risk factors for PTLD before transplantation (i.e., Epstein-Barr virus [EBV] serostatus of the recipient and the cytomegalovirus [CMV] sero-status of the recipient and the potential donor) and the principal risk factor after transplantation (immunosuppression with antilymphocyte antibody), we analyzed the findings for the first 381 consecutive adult nonrenal transplant recipients seen at Mayo Clinic. In the absence of the other risk factors, the incidence rate of PTLD for EBV-seronegative recipients was 24 times higher (95% confidence interval [CI]: 6.2, 89) than that for EBV-seropositive recipients. The additional risk factors of therapy with OKT3 for rejection and CMV seromismatch (i.e., a negative recipient and a positive donor) each further amplified this risk four- to sixfold. Together, all three risk factors acted synergistically to increase the incidence rate of fatal and/or CNS PTLD by a factor of 654 (CI: 368, 1,162) compared with the low incidence rate (.458 cases per 100 person years) when none of these risk factors were present. Pretransplantation determination of recipient EBV and CMV serostatus can identify a subgroup of patients whose risk for severe PTLD may preclude transplantation.

Human babesiosis, which is caused by infection with the intraerythrocytic malarialike protozoan Babesia microti, has recently been diagnosed with increasing frequency in residents of New England. Diagnosis is difficult because of the small size of the parasite and the sparse parasitemia that is characteristic of most infections with this pathogen. We generated B. microti-specific DNA sequence information by universal primer amplification of a portion of the eukaryotic 16S-like gene; this was followed by direct DNA sequence analysis. Specific primers were synthesized on the basis of this sequence information for use in the polymerase chain reaction (PCR). The PCR-based system demonstrates a strong bias for detection of B. microti as opposed to Babesia gibsoni and does not amplify vertebrate DNA. The analytical sensitivity of the system is approximately three merozoites. Blood specimens from 12 patients with clinically diagnosed and parasitologically confirmed babesiosis from Nantucket Island, Mass., were PCR positive in a blinded test of this procedure. Thus, DNA amplification may provide an adjunct to conventional methods for the diagnosis of human babesiosis and may provide a new means of monitoring therapy or enhancing epidemiological surveillance for this emerging pathogen.

No abstract

Manson and Martin review the clinical controversies surrounding hormone-replacement therapy. 1 The findings of the Heart and Estrogen/Progestin Replacement Study (HERS) suggest reasons to be cautious about the use of hormonereplacement therapy in women who are 65 years of age or older. Of 2763 women (mean age, 67 years) with established coronary heart disease, women who were randomly assigned to receive hormone-replacement therapy had an excess risk of one additional blood clot per 64 women and of one additional gallbladder operation per 69 women during a fouryear period.2,3 Hormone-replacement therapy was significantly associated with worsening urinary incontinence. 4 Side effects of hormone-replacement therapy included breast tenderness and uterine bleeding, and only 70 percent of the women remained adherent to therapy by the end of year 3. 2Manson and Martin did not include stroke in their evaluation of benefits and risks. Among 652 women (mean age, 71 years) who had had a transient ischemic attack or nondisabling stroke, women who were randomly assigned to receive oral estradiol did not have lower rates of death or stroke. 5 The risk of fatal stroke was significantly increased (relative risk, 3.86; 95 percent confidence interval, 1.09 to 13.63) with the use of estrogen therapy. 5Before older women begin receiving hormone-replacement therapy, clinicians should inform them of the increased risk of blood clots, gallbladder disease, urinary incontinence, and fatal stroke. Clinicians should correct the misperception that hormone-replacement therapy is cardioprotective, since both the Women's Health Initiative 6 and HERS reported an increased risk of cardiovascular events in the first one to two years of use. Clinicians should alert women that, in 1999, the Food and Drug Administration removed the treatment of osteoporosis as an indication for estrogen therapy because of the lack of evidence from randomized trials of the effect of estrogen on the risk of fracture.