Efficacy, safety, and risk-benefit analysis of adjuvant interferon alfa-2b in melanoma.

A recently completed Eastern Cooperative Oncology Group trial, E1684, has shown that adjuvant therapy with high-dose recombinant interferon alfa-2b (rIFN-alpha 2b) has a significant impact on relapse-free and overall survival in melanoma patients at high risk of recurrence. Adjuvant rIFN-alpha 2b increased the median overall survival to 3.82 years in the treatment group compared with 2.78 years with observation and yielded a 5-year survival rate of 46% versus 37% with observation. This is the first adjuvant therapy to significantly extend survival in this patient population (P = .0023, one-sided). The response to therapy was greatest among those patients with clinical evidence of nodal metastasis. The toxicity associated with this regimen was substantial but tolerable. Approximately 78% of patients treated with rIFN-alpha 2b experienced grade 3 or greater toxicity, and dose modifications were required for 37% and 36% of patients in the induction or maintenance phase, respectively. Quality-of-life-adjusted survival analysis has shown that, despite the toxicity associated with rIFN-alpha 2b therapy, the quality-of-life-adjusted time gained with rIFN-alpha 2b therapy outweighs the reduced quality of life associated with treatment toxicity and relapse. These data support the use of high-dose rIFN-alpha 2b as adjuvant therapy in melanoma patients at high risk of recurrence.

Enhancing parental competencies for high risk mothers: an evaluation of prevention effects.

A three-year study examined the effects of two prevention programs for sole-support mothers with preschool-aged children. A life-skills, esteem-building group program was compared with a group program teaching life skills combined with parent training. A non-randomized, repeated-measures design was employed with measures occurring before, after, and one year after each program for participants in the two intervention groups and for a group of matched comparison subjects. The lack of competency enhancement effects appeared to be a function of reduced exposure of subjects to the interventions. In addition, there was no support for the connection between short-term competency enhancement and long-term prevention of disorder. The negative results serve, in this report, as a cautionary tale highlighting the difficulties in conducting evaluations of primary prevention. It would appear that program planners are placed in a Catch-22 situation by trying to justify the effectiveness of primary prevention through short-term, low-intensity approaches.

Styles of conflict resolution and cooperation between divorced parents: effects on child behavior and adjustment.

Findings from a study of family functioning following divorce suggest ways in which the parents' ongoing relationship-both as former spouse and as coparent-may moderate the effects of divorce on their children. Level of conflict in the "spouse" role was found to be less predictive of children's adjustment than were degree of cooperation and style of conflict resolution in the "coparent" role. Implications for intervention are considered.

Youth at risk: definitions and implications for service delivery.

The literature on adolescent risk is reviewed, a model of risk that emphasizes risk antecedents and markers is proposed, and an overview is presented of an emergency service delivery strategy that integrates services, emphasizes interagency coordination, and addresses the full range of service needs for youth at risk. Highlights of programs currently in operation are described.

Recent research on family factors and readiness: implications for military leaders.

Past research on the relationship between family factors and military readiness in the Army has suggested that family issues affect retention far more than readiness. New data on individual soldier readiness were analyzed to assess the relative importance of family factors (internal and external family adaptation) compared to unit readiness, longevity, rank, and gender. Family factors were significant predictors, although external family adaptation appeared to be more important than internal family adaptation. Although variables related to retention were more strongly related to family factors than our readiness variables, the differences were less substantial than those reported previously. The data seemed to suggest that reserve-component readiness might be more affected by family stress than the active component and that officer readiness might be more strongly affected by family worries than enlisted personnel readiness, but more research is needed to confirm those results.

Gastric remnant carcinoma.

One hundred cases of gastric carcinoma at The New York Hospital-Cornell Medical Center included 7 cases of gastric remnant carcinomas, which were analyzed and compared with prior reports in the literature. Gastric remnant carcinoma is a distinct entity, noted in greatest incidence beginning approximately 15 years after surgery for benign gastric disease. Although the etiology is unknown, the high incidence of bile reflux and concomitant existence of histologic change may account for a premalignant environment in which the stomach assumes some absorptive function. Such new activity may result in the influx of potentially carcinogenic compounds and subsequent tumor development. Early diagnosis of remnant carcinoma following gastric surgery is important to improved prognosis, and endoscopic followup is recommended for all such patients beginning 10-15 years postoperatively.

Reed-Sternberg cells in Hodgkin's disease contain fibronectin.

Reed-Sternberg cells in the lymph nodes from five patients with Hodgkin's disease were studied. Indirect immunofluorescence on fixed sections with a monospecific anti-serum to fibronectin revealed abundant cytoplasmic fibronectin in approximately 90% of the Reed-Sternberg cells. In addition, the cells were shown by immunofluorescence to contain polyclonal IgG; however, factor VIII antigen, albumin, fibrinogen, alpha-2-macroglobulin, anti-thrombin III, and ceruloplasmin were not present. The abundant cytoplasmic fibronectin suggests that Reed-Sternberg cells are derived from tissue macrophages.

Torsion of accessory fallopian tube: ultrasound findings in two premenarchal girls.

The ultrasound findings of two cases of fallopian tube duplication, both of which had undergone torsion, are described. Two premenarchal girls were examined with ultrasound because of clinical evidence of pelvic pathology. Both were found to have complex cystic structures that on surgery and subsequent pathological examination were shown to be twisted accessory fallopian tubes. Accessory fallopian tubes have been reported to occur in 6-13% of selected patient groups. To our knowledge, torsion of an accessory tube has not been reported in the literature.

On the virulence of group A streptococci: evidence for virulence factors other than M-protein and capsule.

Group A streptococci from parent cultures (PC) of six different serotypes were selected by rotation with human blood (RHB) or by serial passage via intraperitoneal inoculation in mice (MP). M-protein content of PC, RHB and MP streptococci of each serotype was determined in quintuplicate by radial immunodiffusion against type-specific antisera. Hyaluronic acid content was determined in quintuplicate colorimetrically after treatment of streptococci with hyaluronidase. Data were subjected to variance analysis. LD(50) for mice of PC, RHB and MP streptococci, inoculated intraperitoneally, was also determined. It was observed that MP streptococci virulent for mice were rich in M-protein and hyaluronic acid. However, RHB streptococci of M-protein and hyaluronic acid content similar to MP streptococci were not virulent for mice. This dichotomy with respect to mouse virulence infers the existence of as yet unidentified streptococcal virulence factors, in addition to M-protein and capsule.

Premarital counseling and marital satisfaction among civilian wives of military service members.

Wives' marital satisfaction was evaluated as a function of a premarital counseling typology in an analysis of data from several thousand military couples surveyed in 1992. Among couples who jointly reported participation in premarital counseling, results indicated that both having premarital counseling and reporting higher satisfaction with the counseling experience were associated with higher levels of marital satisfaction. Among couples who disagreed about having had premarital counseling, results were still favorable but less consistent. Implications for clinical practice are discussed.

Advanced diffuse non-Hodgkin's lymphoma. Analysis of prognostic factors by the international index and by lactic dehydrogenase in an intergroup study.

BACKGROUND: Recent data have suggested that there are no differences among various anthracycline-based chemotherapy regimens [including cyclophosphamide, vincristine, methotrexate, and prednisone (CHOP), methotrexate, calcium leucovorin, bleomycin, doxorubicin, cyclophosphamide, and dexamethasone (m-BACOD), methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), and cyclophosphamide, doxorubicin, etoposide, prednisone, cytosine arabinoside, bleomycin, vincristine, methotrexate, and calcium leucovorin (PROMACE-cyta-BOM)] in patients with diffuse aggressive lymphomas. Because outcome appears to depend on certain prognostic factors, risk groups can be identified. Therefore, these prognostic factors were examined for their correlations with survival, time-to-treatment failure (TTF), and disease free survival (DFS) in a group of patients with diffuse aggressive non-Hodgkin's lymphoma who were treated on a single randomized trial with either CHOP or m-BACOD. METHODS: From July 1984 to January 1988, 392 patients with diffuse large cell or diffuse mixed non-Hodgkin's lymphoma were enrolled in an Intergroup study and were randomly assigned to treatment with CHOP or m-BACOD chemotherapy. Of these, 325 were eligible for response, toxicity, and survival analysis, and the results were reported. The survival and TTF results now have been updated. The 286 patients who had lactic dehydrogenase (LDH) data available at study entry were analyzed for prognostic features according to the International Index criteria and using Martingale Residuals for proportional hazards regression. RESULTS: There were no differences in survival, TTF, and disease free survival between groups of patients treated with either CHOP or m-BACOD. In addition, analysis using the International Index criteria confirmed that patients in the lower risk groups had better outcome than patients in the higher risk groups (5-year survival was 56 and 58% for low and low/intermediate risk groups, respectively, and 37% and 31% for high/intermediate and high risk groups, respectively). There were, however, no differences in survival, disease free survival, or TTF within any risk group when treatment with CHOP or m-BACOD were compared. In addition, analysis using Martingale residuals for proportional hazards regression identified LDH level (> 3 x normal) as an important prognostic factor that was not captured by the International Index. Thus, 5-year survival was 57% if LDH was normal or below, 42% if LDH was 1-3 x normal, and 21% if LDH was > 3 x normal. CONCLUSION: In patients with advanced diffuse large cell or diffuse mixed non-Hodgkin's lymphoma, there are no differences in outcome that can be attributed to treatment with CHOP vs. m-BACOD; this holds for any prognostic group identified by the International Index. However, the level of LDH at time of study entry is an important prognostic factor that is predictive of survival and may help to identify candidates for future clinical trials.

Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma.

BACKGROUND: In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), as compared with a regimen containing bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and leucovorin (m-BACOD). METHODS: From July 1984 through January 1988, 392 patients were enrolled, 325 of whom (83 percent) were eligible for the analysis and capable of being evaluated. The extent of disease was defined according to standard staging techniques, including bilateral bone-core biopsies in 88 percent of patients. Randomization was stratified according to age (< 60 or > or = 60 years), performance status (0, 1, or other), stage (III or IV), and histologic presentation (diffuse mixed or diffuse large-cell lymphoma). RESULTS: After a median follow-up of four years, there were no significant differences in rates of complete remission, time to treatment failure, disease-free survival, or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD. However, there was more severe and life-threatening pulmonary, infectious, and hematologic toxicity associated with the m-BACOD regimen. In an attempt to measure the importance of dose intensity in the 325 patients who could be analyzed, we retrospectively calculated dose intensity (measured in milligrams per square meter of body-surface area per week) and normalized dose intensity (defined as a percentage of the prescribed dose) for all drugs. The median normalized dose intensity for both cyclophosphamide and doxorubicin was found to be greater in the patients treated with CHOP than in those treated with m-BACOD. CONCLUSIONS: For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma, CHOP is superior to m-BACOD, but the role of dose intensity is not yet clear.