Predictive testing for Huntington disease in Canada: adverse effects and unexpected results in those receiving a decreased risk.

By January 1, 1991, a total of 388 persons had enrolled in the Canadian collaborative study of predictive testing for Huntington disease (HD). Of these participants, 105 persons have been given a decreased risk result. Contrary to expectations, approximately 10% of persons with a decreased risk result have had psychological difficulties coping with their new status. Here, we describe the individual responses of 6 such persons and experimental themes emerging after following these persons for up to 2 years. Individuals who are more likely to suffer an adverse reaction to a decreased risk result include those persons who have made irreversible decisions based on the belief they would develop HD or those who had unrealistic overoptimistic expectations of the positive effects of a decreased risk result. In contrast to those receiving an increased risk result, the most vulnerable time for persons receiving a decreased risk result is between 2 and 12 months after learning the outcome. The need for assessment and counselling of participants in predictive testing programs, even when there is a decreased risk result, is emphasized.

Long-term effects of sibling incest.

Although sexual abuse of children is recognized as a serious problem, sibling incest has received relatively little attention. A distinction has been made between power-oriented sibling incest and nurturance-oriented incest. The authors review the relevant literature and present four clinical examples. The cases illustrate the broad range of sibling incest and demonstrate its effects, including the long-term consequences for the perpetrator. Lasting difficulties in establishing and maintaining close relationships, especially sexual ones, are prominent features of each case. Without denying the occurrences of benign sex-play between siblings, the authors emphasize exploitation and abuse as pathogenic aspects of sibling incest.

Analysis of "early" thymidine/inosine protection as an adjunct to methotrexate therapy.

The feasibility of "early" thymidine and inosine protection of methotrexate (MTX) toxicity is evaluated in this paper. This approach is based on the proposition that the most vulnerable period for susceptible host cells to MTX toxicity is an interval following a pulse of MTX when the MTX monoglutamate level is high. In contrast, tumor cells that accumulate active MTX polyglutamyl derivatives are exposed to the cytotoxic effects of MTX, not only when the monoglutamate levels are high, but also over the much longer interval during which polyglutamyl derivatives are retained within these cells. The protecting agents employed, thymidine and inosine, circumvent the antipurine and antipyrimidine effects of MTX, but neither agent inhibits the transport or the polyglutamylation of MTX. Nucleoside protection given over 6 hours after MTX markedly decreased toxicity to normal BDF1 mice at MTX doses up to 150 mg/kg/day for 3 consecutive days. The LD10 for unprotected mice was 14 mg/kg/day, while the LD10 for the protected mice was 114 mg/kg/day, a greater than eightfold increase in the drug dose delivered. MTX with early nucleoside protection produced a 50% increase in median life span in tumor-bearing mice at doses of drug that were toxic to unprotected mice. Flow cytometric analyses indicated that consecutive daily pulses of MTX with early nucleoside protection alter the cell cycle distribution. By 24 hours after the last of three daily pulses of MTX, the G1 component was maximal (80% of the cell population), with less than 2% of the cells in G2M and 17% of the cells in S phase. This distribution persisted for 24 hours, after which a normal pattern emerged, a process that was accelerated by neither thymidine/inosine nor leucovorin. These studies support the concept that toxicity to the host is initiated largely in the interval shortly after MTX administration. The data indicate that early nucleoside protection permits the repetitive administration of much higher doses of MTX than can be given with MTX alone. This approach may be useful not only in the treatment of human neoplasms but in the treatment of other disorders, such as rheumatoid arthritis, psoriatic arthritis, or psoriasis. Finally, this paper considers the potential advantages of early thymidine/inosine protection in comparison to leucovorin rescue with the administration of low or moderate doses of MTX.

Bone marrow examination in small cell carcinoma of the lung. Comparison of trephine biopsy with aspiration.

Bone marrow examinations in 146 patients with small cell carcinoma of the lung were reviewed. The results of trephine biopsy and aspiration were compared in 128 patients in whom both techniques were performed. Twenty-seven of the 128 examinations (21.2%) showed positive aspirates and 30 biopsies (23.4%) revealed metastatic disease. The overall agreement between the aspirates and biopsies was 96.1%. Thirty-one patients (24.2%) had metastatic tumor in either aspirate or biopsy: 4 of these (12.9%) had a positive biopsy with negative aspirate, and 1 (3.2%) showed a positive aspirate and negative biopsy. The Jamshidi needle was used, yielding an average of 4.1 cm of core material per biopsy. The authors conclude that bone marrow biopsy using the Jamshidi needle is equivalent to aspiration. Although both procedures are complementary, a satisfactory specimen obtained with the Jamshidi needle alone may yield nearly equal detection to the combined procedures. Some guidelines for obtaining an optimal biopsy specimen are suggested.

Delivery of medical care in an urban core.

Seventy-six families who had an annual income under $3000, and who lived within half a mile of a medical centre were interviewed in their own homes. Their attitudes and opinions towards health care delivery service, family health and medical personnel, were obtained. They were found to be well aware of the freedom of choice which they possess by virtue of their medical registration certificate and the majority chose to go to private physicians for their care. As high as 55% of the consumers were chronically afflicted. Of these, 65% made medical visits every six weeks, and 20% went weekly. Forty per cent made well-care visits, and only 5% received no care at all. The data demonstrate a degree of satisfaction with, and acceptance of, health delivery service in this specific urban area.