Risk factors for human T cell lymphotropic virus type II infection among the Guaymi Indians of Panama.

To examine risk factors for human T cell lymphotropic virus type II (HTLV-II) infection, a case-control study was conducted among the Guaymi Indians of Panama. In females, HTLV-II seropositivity was associated with early sexual intercourse (15 years; odds ratio [OR], 2.50; 95% confidence interval [CI], 1.11-6.14) and number of lifetime sex partners. One partner increased risk of seropositivity by 30% (OR, 1.30; CI, 1.05-1.64), and risk increased with number of partners. Similar risk was associated with number of long-term sexual relationships. Among males, intercourse with prostitutes was associated with HTLV-II seropositivity (OR, 1.68; CI, 1.04-2.72). These data support a role for sexual transmission in HTLV-II infection. Association of seropositivity with primary residence in a traditional village (OR, 3.75; CI, 1.02-15.38) and lack of formal education (0 vs. >6 years [OR, 3.89; CI, 1.67-9.82]) observed in males may reflect differences in sexual practices associated with acculturation.

Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectional study to assess four candidate biomarkers of immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus type I (HTL V-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- and HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients.

Vaginal clear cell adenocarcinoma in the United States.

We elected to examine available information from several sources to approximate the annual number of cases of vaginal adenocarcinoma in the United States for recent years. Data were obtained from the Registry of Hormonal Transplacental Carcinogenesis, the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute, the National Cancer Databank of the American College of Surgeons Commission on Cancer, and a survey of gynecologic oncologists practicing in the United States. In 1990 a total of 33 new cases and 11 recurrences were reported, while in 1991 23 new cases and 8 recurrences were reported. Neither SEER nor the Registry appear to provide adequate surveillance for this rare disease. Phase III clinical trials are not feasible, given the small number of patients. Statistically effective phase II one-armed studies to investigate new agents in the treatment of advanced or recurrent vaginal clear cell cancer may be possible. Effective mobilization of patients and physicians will be required for such trials to be completed in a timely manner.

Diethylstilbestrol revisited: a review of the long-term health effects.

PURPOSE: To review the literature on the long-term health effects of exposure to diethylstilbestrol (DES) among women prescribed DES during pregnancy (DES mothers), among their children exposed inutero to the drug (DES sons and daughters) and among the progeny of these exposed sons and daughters (DES grandchildren). DATA SOURCES: English-language articles were identified through MEDLINE and CANCERLIT searches and through review of the bibliographies of identified articles. STUDY SELECTION: All human studies relevant to long-term health effects of exposure to DES were reviewed. DATA EXTRACTION: Descriptive data on existing DES cohorts were extracted from early publications. Risk estimates for health effects were extracted from published reports. DATA SYNTHESIS: An estimated 5 to 10 million Americans received DES during pregnancy or were exposed to the drug in utero. Exposure to DES has been associated with an increased risk for breast cancer in DES mothers (relative risk, < 2.0) and with a lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to 1/10,000. The association between DES exposure and testicular cancer in DES sons remains controversial. Exposure to DES has also been linked to reproductive tract abnormalities in DES sons and daughters that consist of immune system disorders and psychosexual effects. No evidence for transgenerational effects currently exists. Recommendations for screening persons exposed to DES are reviewed. CONCLUSIONS: Further research is needed to define long-term health effects related to DES exposure. Such research would provide a basis for counseling persons exposed to DES and would further understanding of environmental and pharmacologic compounds similar to DES.

Arterial thrombosis associated with granulocyte-macrophage colony-stimulating factor (GM-CSF) administration in breast cancer patients treated with dose-intensive chemotherapy: a report of two cases.

The occurrence of arterial thrombosis reported in other breast cancer series has largely been confined to the upper extremities, ipsilateral to a previous mastectomy site and clinically manifest as cerebral vascular accidents. This case report describes 2 patients who experienced iliac artery thrombosis temporally related to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) and dose-intensive chemotherapy for metastatic breast cancer. A review of the literature concerning arterial thrombosis as relevant to breast cancer treatment and GM-CSF is included.

Developing strategies for intervention and prevention in hereditary breast cancer.

Prophylactic mastectomy, intensified breast cancer screening, and the use of chemopreventive agents have all been recommended to reduce breast cancer risk in women with a family history of breast cancer. Yet, little is currently known about the efficacy of these approaches in reducing breast cancer mortality. The recent identification of BRCA1 and the localization of BRCA2 lend urgency to the need to assess breast cancer intervention and prevention strategies for women likely to carry germline mutations at these loci. At present, families with a history consistent with a BRCA1 or BRCA2 mutation should be tested within the confines of a research protocol and encouraged to participate in intervention and prevention trials. Both retrospective studies and prospective clinical trials are critically needed. While randomized clinical trials would be the optimal mechanism to assess the relative efficacy of these potential interventions, no consensus was obtained as to whether such a trial would be feasible because of strong patient preference for intervention type. It is likely that optimal intervention and prevention strategies will consist of a combined approach to risk reduction. Participants must be appropriately informed of the potential risks as well as the potential benefits of such testing. The potential risks of testing for genetic susceptibility include not only potential psychosocial harm that may result from learning one's carrier status, but also the potential for altered family relationships and insurance and job discrimination. Participants and their family members must be counseled concerning the implication of their test results.