Phase I trial and pharmacokinetics of aziridinylbenzoquinone (NSC 182986) in humans.

2,5-Diaziridinyl-3,6-(carboethoxyamino)-1,4-benzoquinone (AZQ) is a rationally designed antitumor agent which possesses sufficient lipid solubility to allow central nervous system penetration as well as adequate aqueous solubility for drug formulation and administration. We have conducted a Phase I trial of AZQ in 40 previously treated patients with advanced cancer. The drug was given as a 15-min i.v. infusion on Days 1 and 8 of a 28-day cycle. Seven dose levels ranging from 1 to 25 mg/sq m were studied with 3 to 11 patients treated at each level. Sixty-nine evaluable cycles of AZQ were administered. The major toxicity was myelosuppression, with the nadir in white blood cells and/or platelet count occurring at Days 15 to 20 of the cycle and first appearing at doses greater than 10 mg/sq m. The highest tolerated dose was 20 mg/sq m, and this dose is recommended for Phase II trials. Other toxicities were mild nausea, slight alopecia, and anemia. Plasma pharmacokinetics was studied in 11 patients by a high-performance liquid chromatography assay. Plasma decay curves could be fitted to a two-compartment open model of drug disappearance with a dose-independent terminal half-life of 33.3 +/- 4.5 (S.D.) min. Cerebrospinal fluid AZQ levels were determined in three patients and revealed readily detectable levels of AZQ.

Central nervous system complications of non-Hodgkin's lymphoma. The potential role for prophylactic therapy.

In 38 patients with non-Hodgkin's lymphoma, involvement of the central nervous system (CNS) by malignant lymphoma developed during an eight year period. All patients had lymphomatous meningitis; clinical involvement of the spinal nerves or cranial nerves suggested the diagnosis. Spinal fluid was abnormal in 97 per cent of the patients although a positive cytology could be documented in only 67 per cent by lumbar puncture. The histology in 82 per cent of the patients was diffuse. Involvement of the CNS in nodular lymphoma was uncommon (3 per cent), and the histology in virtually all of these patients had converted to diffuse. At the time of diagnosis of CNS disease, 95 per cent of the patients had other evidence of advanced disease; 66 per cent had bone marrow involvement. In only 18 per cent of the patients did CNS disease develop while they were in clinical remission. Eighty-five per cent of the patients treated with whole brain irradiation and intrathecal chemotherapy had a good clinical response. Knowledge of these risk factors permits definition of a group of patients who may benefit from CNS prophylaxis.

Consent forms: how to determine and improve their readability.

This study investigated the reading level estimates of cancer clinical trial consent forms from actively accruing studies at the Medicine Branch and the Clinical Pharmacology Branch of the National Cancer Institute. Forty-four consent forms were analyzed using the SMOG formula. Readability levels ranged from grade 12 to grade 17.5 (mean = 14.3). The conclusion was that these consent forms were written above most subjects' reading levels. The usefulness of consent forms could be improved significantly by using readability formulas, applying rewriting techniques, and being aware of subjects' comprehension levels. This paper suggests a number of strategies that nurses can use to enhance comprehension of the information contained in informed consent documents.

Practice patterns during the third stage of labor: the effect of physician age and specialty.

BACKGROUND: Elective manual removal of the placenta and routine uterine exploration following vaginal delivery are controversial procedures. Although advocated in the past, little is known about current attitudes and practices related to these procedures. METHODS: Using a mailed questionnaire, we surveyed all 178 Iowa obstetrician-gynecologists and a random sample of 163 Iowa family physicians to determine their practice patterns related to selected aspects of the third stage of labor. The data were analyzed using odds ratios and multiple logistic regression. RESULTS: The analysis was based on answers from 302 physicians. Physicians in the oldest age quartile were three times more likely than physicians in the youngest age quartile to routinely explore the uterus after a vaginal delivery (P < .01). After controlling for specialty, younger physicians were more likely to believe that manual removal of the placenta is a risk factor for endometritis (adjusted odds ratio [OR] 0.7 for each 10-year increase in age, 95% confidence interval [CI] 0.6 to 1.0). Controlling for age, family physicians were more likely than obstetrician-gynecologists to routinely order prophylactic antibiotics after manually removing the placenta (adjusted OR 2.0, 95% CI 1.1 to 3.7). CONCLUSIONS: Both physician age and specialty were associated with selected practice patterns involving the third stage of labor. Older physicians were less likely to believe that manually removing a placenta increases the risk of postpartum endometritis, and they were more likely to routinely explore the uterus after a vaginal delivery.

Differences in practice patterns between obstetricians and family physicians: use of serum screening.

OBJECTIVE: Our purpose was to compare the use of the Iowa Expanded Serum Screening program (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol) by obstetricians and family physicians. STUDY DESIGN: A registry was used to identify all obstetricians (160) and family physicians (404) who practice obstetrics in Iowa. A questionnaire exploring attitudes and practice patterns related to serum screening was mailed to these physicians. RESULTS: The response rate was 80.3% overall. There were significant differences in the offering of serum screening (p < 0.001) for following three responses: obstetricians were more likely to offer screening through the Iowa Expanded Serum Screening Program than were family physicians (89.3% vs 57.2%) and less likely to offer screening outside the state program (9.9% vs 39.0%), whereas family physicians were more likely to not offer screening (0.8% vs 3.8%). When the responses of the physicians who offer screening were analyzed, several differences emerged: (1) obstetricians were more likely than family physicians to offer screening to all obstetric patients (99.2% vs 92.1%, p < 0.05), whereas family physicians were more likely to offer testing to patients with perceived risks for neural tube defects or chromosomal abnormalities and to those patients who requested it, (2) obstetricians were more likely to recommend screening than family physicians (39.0% vs 25.7%, p < 0.05), who more often discouraged testing, although the latter did not reach statistical significance, (3) family physicians more than obstetricians felt that screening was not necessary if the patient would not terminate the pregnancy for neural tube defects (41.6% vs 19.1%, p < 0.001) or chromosomal abnormalities (39.7% vs 21.4%, p < 0.01), and (4) obstetricians used nurses to counsel patients to a much greater extent than family physicians did (44.6% vs 14.0%, p < 0.001). CONCLUSION: There is a significant difference in practice patterns between obstetricians and family physicians in their reported use and presentation of maternal serum screening. Guidelines based on outcome studies should be developed and followed by obstetricians and family physicians.

Persistent immunologic abnormalities in long-term survivors of advanced Hodgkin's disease.

Immunologic studies were done on 47 long-term survivors of Hodgkin's disease who had been treated with MOPP chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone). Percentages of E rosettes and mitogen-induced lymphocyte proliferation were significantly reduced compared to those in normal control subjects. There was no tendency for these abnormalities to return to the normal range with increasing disease-free intervals. No abnormalities of B-cell number or function were detected. Long-term survivors of advanced diffuse histiocytic lymphoma treated with comparable chemotherapy, who served as a control population, had significantly higher percentages of E rosettes and no reduction in mitogen-induced lymphocyte proliferation. Thus these persistent immunologic abnormalities cannot be attributed to chemotherapy alone. The presence of similar immunologic abnormalities in untreated patients with Hodgkin's disease of all stages and in patients cured by either MOPP or radiotherapy suggests that depressed cellular immunity may be an inherent characteristic of the person in whom Hodgkin's disease develops.