4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D-arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia.

We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.

Phase I and II clinical and pharmacological study of 4-demethoxydaunorubicin (idarubicin) in adult patients with acute leukemia.

Fifty-two adults treated previously with either acute leukemia (43 patients) or blastic-phase chronic myelogenous leukemia (nine patients) received 4-demethoxydaunorubicin (20 to 45 mg/sq m) i.v. over 2 to 3 days. Three of the ten patients with acute lymphocytic leukemia achieved a complete remission (CR) lasting 5 to 7 weeks. Five of the 28 patients with acute nonlymphocytic leukemia achieved a CR lasting 5 to 80 weeks. All remissions were induced with one course of treatment with a median time to CR of 28 days (range, 22 to 40 days). None of the patients with blastic chronic myelogenous leukemia or secondary leukemia achieved a CR. The drug was well tolerated; mucositis (36%), nausea and vomiting (35%), and hepatic dysfunction (26%) were the most common side effects. Pharmacokinetic observations on five patients demonstrated multiphasic clearance of 4-demethoxydaunorubicin and extensive formation and prolonged retention of 4-demethoxy-13-hydroxydaunorubicin; that metabolite accumulated in plasma on repeated daily dosing. 4-Demethoxydaunorubicin has sufficient antileukemic activity in both acute lymphocytic leukemia and acute nonlymphocytic leukemia to warrant a prospective comparison, in combination regimens, against the conventional anthracyclines, daunorubicin and/or doxorubicin.

A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy.

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.

Multifocal central nervous system damage caused by toluene abuse.

Four toluene abusers had evidence of severe multifocal central nervous system damage. Impairment of cognitive, cerebellar, brainstem, auditory, and pyramidal tract function, as well as CT evidence of cerebral cortical, cerebellar, and brainstem atrophy, have been noted. In addition, we found opsoclonus, ocular flutter, and ocular dysmetria. All three patients tested had abnormal brainstem auditory evoked potentials, indicative of brainstem dysfunction. The patient with opsoclonus had CT evidence of brainstem, cerebellar, and cerebral cortical atrophy.

Accelerated development of pulmonary complications due to illicit intravenous use of pentazocine and tripelennamine.

To gain information concerning the natural history and prevalence of pulmonary gas exchange abnormalities resulting from intravenous drug abuse, 45 intravenous drug users were studied. Twenty subjects used a mixture of the synthetic opiate pentazocine and the antihistamine tripelennamine, which, under the street name T's and B's, has become very popular in some urban areas as an available substitute for heroin. Compared with the 19 heroin addicts studied, the pentazocine and tripelennamine users had a significantly shorter mean duration of intravenous drug abuse (2.7 +/- 0.4 years versus 7.6 +/- 0.9 years, p less than 0.01), a greater frequency of respiratory symptoms (75 percent versus 36 percent, p less than 0.05), a significant reduction in the mean diffusing capacity of the lung for carbon monoxide (58.4 +/- 3.3 percent predicted versus 75.5 +/- 5.6 percent predicted, p less than 0.01), and abnormal responses to submaximal steady-state exercise testing. The intravenous use of pentazocine and tripelennamine and probably most other drug preparations intended for nonparenteral use represents a particularly noxious form of drug abuse that may lead to early respiratory complications in a large proportion of users.

Impotence associated with compulsive gambling.

A 49-year-old patient who presented initially for treatment of inhibited sexual desire and secondary impotence was found to meet DSM-III criteria for compulsive gambling. The relationship between sexual dysfunction and gambling is discussed. Compulsive gambling should be considered in the differential diagnosis of impotence, and a sexual history should be obtained from patients with compulsive gambling.

A case of catatonia induced by bacterial meningoencephalitis.

A 51-year-old man with renal cell carcinoma developed lethargy, disorientation, and fever; shortly thereafter, he had several episodes of sudden-onset catatonia. He was found to have bacterial meningoencephalitis and frontal lobe EEG abnormalities. Treatment with antibiotic and phenytoin was started, and the catatonic episodes subsided. The authors emphasize the need for a diligent investigation of all possible causes of sudden-onset catatonic syndrome and recommend that bacterial meningoencephalitis be added to the list of differential diagnoses of acute catatonia.

Pathological gambling in hospitalized substance abusing veterans.

BACKGROUND: Previous studies have suggested that pathological gambling and substance abuse may be more likely to occur together than expected by chance. We examined this possibility as well as explored psychosocial and diagnostic variables that may be associated with this coincidence. METHOD: Of 276 patients who were administered the South Oaks Gambling Screen, 134 subjects were interviewed using a semistructured comprehensive psychiatric questionnaire. Data analysis utilized Student t tests or analysis of variance routines. RESULTS: The rate of comorbid pathological gambling in the sample was 33% (92 of 276). A high rate of comorbid substance abuse and pathological gambling was associated with a positive history of childhood experiences of gambling in the family group (p = .001) and with larger family size (p = .001). In addition, current alcohol consumption was significantly higher (p = .007) in the pathological gambling group. CONCLUSION: Comorbidity of substance abuse and pathological gambling is common in substance abuse patients in a VA hospital. Substance abuse treatment programs should identify patients with pathological gambling and include treatment interventions that address both problems.

Why should physicians recognize compulsive gambling?

Compulsive gambling, which was recently recognized as a separate and primary illness, is a chronic disease that has as one of its facets poor impulse control. The illness is likely to be encountered by primary care physicians who look for it. A complete history, focusing on the destructive impact of gambling on the person's ability to function, and physical examination, including a search for coexisting cardiovascular disease and alcohol or substance abuse, are recommended for these patients. Diagnostic criteria have been described and shown in table form, as have therapeutic options. This condition is treatable, and the earlier it is discovered, the less damage will be done to the psychological, emotional, social, and financial well-being of the patient.

Seasonal affective disorder. Shedding light on a dark subject.

Seasonal affective disorder (SAD) appears to be a disturbance of circadian rhythm caused by desynchronization between the solar clock and the human biologic clock during seasons of short photoperiods. The supplemental bright light of phototherapy resynchronizes the disturbed rhythm; however, a comprehensive theory to explain the mechanism of phototherapy is lacking. Future research on the action of melatonin and serotonin and the photochemical effect of light in relation to possible circadian rhythm disorders should help us to better understand and treat not only SAD but other conditions such as jet lag, premenstrual syndrome, eating disorder, and carbohydrate-craving obesity.

The supervisor's role with the problem drinker employee.

In a large company, a group of problem drinker employees selected from the Alcoholic Rehabilitation Program at Illinois Bell, and a group of supervisors of such employees were participants in the study. Questionnaires as well as interviews were utilized. Comparative tables were discussed. A definite, yet flexible role of the supervisor was seen operative throughout the different processes of recognition, confrontation, referral, and treatment. Certain conclusions were drawn from the perspective of the patients, the supervisors, and the company.

Cervix carcinoma: treatment with combination cisplatin and bleomycin.

Thirty patients with metastatic carcinoma of the cervix were treated with a combination of cisplatin and bleomycin. Thirty patients were evaluable for toxicity and 24 were evaluable for response. Thirteen patients achieved a partial remission for an objective response rate of 54% with a median duration of 3.5 months. The response rate for extrapelvic disease without prior radiation was 57% while the response rate for disease recurring in the previously irradiated pelvic area was only 36%. Response rates were higher in tumors with nonsquamous histology. Survival times for responders and nonresponders were not significantly different. Significant toxicity was observed. It is concluded that the combination of high-dose cisplatin and bleomycin infusion in patients with recurrent cervix cancer has an improved response rate. However, these responses are of short duration and drug toxicity is significant. The role of this combination for adjuvant studies is discussed.

Phase I-II trial of mitoxantrone in acute leukemia.

Mitoxantrone was evaluated in a multi-institution trial to define the effective dose for treating acute leukemia, to evaluate its toxicity, and to assess the induction rates for the different types of acute leukemia. Fifty-seven patients have been treated. Of the 24 patients receiving mitoxantrone (10 mg/m2/day X 5), one of nine with acute nonlymphoblastic leukemia (ANLL) in relapse, one of five with acute lymphoblastic leukemia in relapse, and one of seven with blastic chronic myelogenous leukemia achieved remission. At a dose of 12 mg/m2/day X 5, seven of 16 patients with ANLL in relapse, none of six with acute lymphoblastic leukemia in relapse, and one of five with blastic chronic myelogenous leukemia achieved remission. At both dose levels, there was no response in patients who had failed to achieve a prior remission. Toxic effects included nausea/vomiting, stomatitis, and hepatic dysfunction. Nine of the 57 patients treated experienced cardiac events but cardiac toxicity seemed clinically significant in only three. We conclude that mitoxantrone, at a dose of 12 mg/m2/day X 5, is effective therapy for ANLL. Trials combining mitoxantrone with other agents are needed.

Case managed residential care for homeless addicted veterans. Results of a true experiment.

OBJECTIVES: The effectiveness of case-managed residential care (CMRC) in reducing substance abuse, increasing employment, decreasing homelessness, and improving health was examined. METHODS: A five-year prospective experiment included 358 homeless addicted male veterans 3, 6, and 9 months during their enrollment and at 12, 18, and 24 months after the completion of the experimental case-managed residential care program. The customary control condition was a 21-day hospital program with referral to community services. RESULTS: The experimental group averaged 3.4 months in transitional residential care with ongoing and follow-up case management for a total of up to 1 year of treatment. The experimental group showed significant improvement compared with the control group on the Medical, Alcohol, Employment, and Housing measures during the 2-year period. An examination of the time trends indicated that these group differences tended to occur during the treatment year, however, and to diminish during the follow-up year. CONCLUSIONS: Within groups, significant improvements were observed with time from baseline to all posttests on the four major outcomes. We learned, however, that veterans had access to and used significant amounts of services even without the special case-managed residential care program. This partially may account for improvements in the control group and may have muted the differences between groups.