Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes.

BACKGROUND: The use of a high dose regimen of interferon-alpha-2b (IFN) has recently been demonstrated to benefit patients with resected high risk melanoma. The incidence of melanoma is rising rapidly, and the use of this regimen is becoming increasingly common. IFN has been associated with numerous psychiatric side effects. METHODS: The authors describe four melanoma patients treated with adjuvant IFN who developed a manic-depressive syndrome or mood instability with therapy, and they review the literature on mania and the mixed affective syndromes associated with IFN. RESULTS: The authors suggest that IFN may induce a mixed affective instability, and that patients risk developing hypomania or mania as IFN doses fluctuate or as IFN-induced depression is treated with antidepressants alone. Mania is particularly associated with dose reductions or pauses in IFN treatment. The risk of mood fluctuation continues after treatment with IFN stops, and patients should be monitored for 6 months following completion of therapy. Gabapentin appeared effective as monotherapy for acute mania, as an antianxiety agent, as a hypnotic, and as a mood stabilizer in these individual cases. CONCLUSIONS: Mania and mood instability can occur in patients being treated with IFN therapy for melanoma. In this study, gabapentin was an effective mood-stabilizing agent for these patients.

Iatrogenic acute estrogen deficiency and psychiatric syndromes in breast cancer patients.

The change of estrogen function, represented by amenorrhea or hot flashes, that results from breast cancer treatment may increase the risk of major depressive disorder in those women undergoing treatment for breast cancer. This pilot study describes the course of menopausal symptoms and the incidence of depression in 21 patients who were likely to become acutely estrogen deficient during treatment for breast cancer. These included women who lost menses during chemotherapy, who suddenly stopped estrogen replacement therapy (ERT), or who started tamoxifen. Eight patients (38%) developed major depressive disorder, the majority within 6 months of starting treatment. Twenty patients (95%) had dysphoria and/or insomnia. Fourteen patients (66%) had hot flashes. While this is only pilot data, these data suggest that breast cancer patients whose treatment precipitates menopausal symptoms should be targeted for diagnosis of depression and treated if diagnosed.

Quality of life for adult leukemia survivors treated on clinical trials of Cancer and Leukemia Group B during the period 1971-1988: predictors for later psychologic distress.

BACKGROUND: To identify predictors of psychosocial adjustment for survivors of adult acute leukemia, the adaptation of 206 survivors (77% with acute myelogenous leukemia, and 23% with acute lymphocytic leukemia) treated on any of 13 Cancer and Leukemia Group B trials during the period 1971-1988 was examined. METHODS: Survivors (median age, 41 years) who were at least 1 year from completion of all treatment (median, 5 years) were interviewed by telephone about psychologic symptoms; social, sexual, and vocational function; and beliefs about control over health. Standardized psychologic instruments were used to evaluate survivors' responses. RESULTS: Most survivors adapted well; however, 14% were 1.5 standard deviations above normal on the Global Severity Index of the Brief Symptom Inventory. Predictors of greater psychologic distress included less education, younger age, anticipatory distress during chemotherapy treatment, and the combination of more medical problems after treatment with poorer family function. Anticipatory nausea and distress during chemotherapy predicted persistent visceral distress later, which occurred with reminders of treatment. Anticipatory vomiting predicted a greater tendency toward cancer-related intrusive thoughts and avoidance of reminders. CONCLUSIONS: Patients experiencing anticipatory distress during treatment who are younger and less educated should be monitored for depressive syndromes later.

Assessments of girl's genital findings and the likelihood of sexual abuse: agreement among physicians self-rated as skilled.

OBJECTIVES: To measure agreement about genital examination findings among physicians who rate themselves as skilled in evaluating children for suspected sexual abuse, to compare these physicians' descriptions and interpretations with consensus standards developed by an expert panel, and to investigate the effects of physician and case characteristics on agreement. STUDY DESIGN: Questionnaires including 7 simulated cases, each consisting of a brief history and 1 photograph of a girl's genitalia, were mailed to random samples of 2 groups: the members of 4 physician organizations concerned with child abuse or pediatric gynecology, and pediatricians at large. Among the surveyed physicians who rated their own skill in evaluating cases of suspected sexual abuse as higher than average, we measured agreement, both overall and between those with the most and with less clinical experience, and assessed their conformity with consensus standard descriptions and interpretations. RESULTS: We received responses from 548 (50.9%) of 1076 physicians; 414 responses (75.5%) were analyzable. Two hundred six physicians (50%) rated themselves as skilled in assessing children for sexual abuse. On average, 45% of these physicians' descriptions and 72.6% of their interpretations conformed with the consensus standards. In 4 cases, between 5% and 20.7% of these physicians described genital findings that the expert panel had considered absent from the photographs. Conformity with standard interpretations tended to be higher in cases with photographs concordant with the accompanying, unambiguous histories (P=.06). The most experienced physicians resembled the expert panel more closely than did the less experienced self-rated skilled physicians in interpreting 3 simulated cases (P< or =.001). CONCLUSIONS: Assessments of girls' genital findings by physicians who rate themselves as skilled in examining children for suspected sexual abuse often differ. In some cases, among physicians who all rate themselves as skilled, assessments made by very experienced physicians may conform more closely to consensus standards than do assessments made by less experienced physicians.

Minimum criteria for reporting child abuse from health care settings.

We evaluated how consistently clinicians of two hospitals reported child abuse and neglect, and the utility of specific, operational criteria for assessing hospital clinicians' compliance with the child abuse reporting laws. To evaluate clinicians' compliance, we audited the medical records of 85 children who had been reported to a child protective service (CPS) agency by clinicians at either of two hospitals and who had been seen at that hospital at least once before the index report of abuse. The time elapsed from first hospital visit to index abuse report among the 85 children averaged 4.3 years. In the children's records, we identified 28 earlier reports to the CPS agency and four episodes that met criteria we developed but that had not been reported. Thus, application of specific criteria resulted in the finding that 28 (88 percent) of 32 suspected abuse episodes were actually reported to the CPS agency (95 percent confidence interval: 76 to 99 percent). In a second phase of the study, we compared the content of 45 reported episodes of child abuse (4) index reports and four earlier reports) to the criteria in order to evaluate their utility. Thirty-five episodes (78 percent) met one of the criteria. Review of the remaining 10 episodes led to the development of one new criterion. We conclude that, although it has been estimated that hospital personnel nationwide report to CPS agencies only 69 percent of the child abuse cases they identify, clinicians at the hospitals we studied reported 88 percent of documented episodes of suspected abuse. We also conclude that specific, operational criteria can help in the assessment of hospital clinicians' compliance with their obligation to report child abuse and neglect.

Quality of life in osteosarcoma survivors.

Charts of 89 osteosarcoma survivors from Massachusetts General Hospital and The Children's Hospital/Dana Farber Cancer Center, who had received primary treatment more than 1 year previously and had no evidence of disease, were reviewed. Sixty-two patients, mean 12 years from diagnosis, agreed to structured interviews. Rates of psychopathology did not differ significantly from the general population. High distress was noted in 13%. Twenty-three normal progeny had been born postchemotherapy to eight women and the wives of five male patients. One pregnancy was complicated by doxorubicin-induced cardiac toxicity. Only two with previous childhood tumors believed themselves infertile. All felt the effort to save the limb was worthwhile. In most, ongoing pain was mild; phantom pain and neuralgia common. Most survivors were in good mental and physical health with the capacity to bear children.

Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. A long-term oncological, functional, and quality-of-life study.

The outcome of treatment of nonmetastatic high-grade osteosarcoma in the distal part of the femur was studied in 227 patients from twenty-six institutions. Eight of the seventy-three patients who had had a limb-salvage procedure and nine of the 115 patients who had had an above-the-knee amputation had a local recurrence, but there was no local recurrence in the thirty-nine patients who had had a disarticulation at the hip. There were no significant differences in the rate of survival or in the duration of the postoperative disease-free period between the three groups. One hundred and nine patients (48 per cent) were alive at an average of eleven years after the operation, and ninety patients (40 per cent) remained continuously disease-free. An additional operation on the limb was necessary more often for patients who had had a limb-salvage procedure than for those who had had an amputation. Function in seventy-eight living patients was assessed with the system of the Musculoskeletal Tumor Society for evaluation of function and by the functional assessment portion of the 1989 scoring system of the Knee Society; the scores were higher for the patients who had had a limb-salvage procedure than for the two groups of patients who had had an amputation. No difference was identified between the groups with regard to the patient's acceptance of the postoperative state, the ability to walk, or the amount of pain. The quality of life was evaluated for twenty-nine patients with a series of complex questionnaires.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of lithium in patients with cancer.

This article reviews the management of lithium in patients who require optimum management of cancer and simultaneous prevention of mania or depression in lithium-sensitive affective illness. Two cases are described. Discussion focuses on whether lithium should be continued during chemotherapy and radiation treatment, the complications that would lead to lithium toxicity in an otherwise stable patient, the likely settings for hypothyroidism, and the role of lithium to stabilize steroid-induced affective changes. The authors conclude that lithium may be withheld 1 or 2 days before cytotoxic chemotherapy and restarted when the patient is able to drink. It may be given as usual through routine radiation treatment, but it should be discontinued during cranial radiation. Calcium, renal, cardiac, and thyroid functions should be monitored.

Treatment-related fatigue and serum interleukin-1 levels in patients during external beam irradiation for prostate cancer.

To define changes in sleep and subjective fatigue associated with localized radiation treatment, and to determine their relationship to interleukin-1B (IL-1), we prospectively followed 15 men, none of whom were depressed during 8 wk of radiation treatment for localized prostate cancer. Each patient rated fatigue daily on a visual analogue scale, recorded hours slept, and completed the Beck Depression Inventory weekly. Serum IL-1, taken at baseline and Fridays, was measured by quantitative enzyme immunoassay. Ranked weekly mean fatigue scores for each subject increased at week 4 (mean, 17 fractions, 1.8 Gy) then plateaued and rose in weeks 6 and 7. In week 6, the last week of full volume radiation, subjects slept most compared to all other weeks including week 7 when treatment was coned down. Ranked serum IL-1 tended to rise between weeks 1 and 4, as fatigue scores rose. These data suggest that localized radiation treatment is associated with increased fatigue and sleep requirement independent of depressive symptoms. Relative serum IL-1 changes may be one signal for the systemic reaction and subjective fatigue associated with the acute effects of radiation.

Pros and cons of fluoxetine for the depressed cancer patient.

When major depression develops in patients with cancer, specific antidepressant treatment should be initiated. Fluoxetine (Prozac) is one of several effective treatments for depression; it is currently the most frequently prescribed antidepressant in the United States. Unfortunately, the information from studies and reports regarding the use of fluoxetine in patients with cancer is limited. This article reviews the properties, drug interactions, and side-effect profiles of fluoxetine and the other antidepressants most relevant to the care of cancer patients. Also discussed are strategies for the prudent prescription of fluoxetine, the tricyclic antidepressants, and the psychostimulants in depressed cancer patients.

Fatigue syndrome due to localized radiation.

For cancer patients, fatigue is a disturbing symptom caused by many factors. Since fatigue is the most common side effect of localized radiation to the breast, this treatment provides a unique opportunity to follow patients prospectively as they develop one type of fatigue. We evaluated the effect of radiation treatment in 15 women with Stage I or II node-negative breast cancer who were otherwise healthy. Fatigue, contrary to our hypothesis, did not increase linearly with cumulative radiation dose over time. It dropped from the first to second week and rose in the third week. The cumulative effects reached a plateau in the fourth week (after an average of 17 fractions), which was maintained during the remaining weeks of treatment. Within 3 wk after treatment, fatigue had diminished. No patient had sustained depressive symptoms. Cardiopulmonary exercise capacity in 5 patients at 6 and 12 wk did not change from just before radiation. Other markers, including reverse triiodothyronine and pulse change with orthostatic stress, did not correlate with subjective fatigue nor cumulative radiation in 15 patients. The curve of the fatigue syndrome during treatment conforms to the adaptation of the organism to a continuing stress and begins to describe a mild fatigue syndrome associated with radiation.

Strategic use of benzodiazepines in cancer patients.

Benzodiazepines have so many uses in cancer patients that the physician may target more than one advantage as he considers choice of drug and dose. Nausea, pain, and anxiety may be treated simultaneously. Since these patients are often taking a number of medications, the simplest regimen has the most benefit. These drugs treat reactive anxiety, insomnia, claustrophobia, and panic disorder. As they treat anticipatory anxiety and phobia, they mitigate anticipatory nausea and a component of post-treatment nausea. With chemotherapy itself, they cause sedation, suppress recall of treatment, limit vomiting, and are seen as desirable by patients. They suppress the restlessness associated with metoclopramide and other dopamine-antagonist antiemetics. The analgesic effects are best seen in conditions of high anxiety, muscle spasm, and deafferentation syndromes. The advantages of sedative and antipsychotic effects may be exploited to suppress the psychiatric complications of high-dose corticosteroids.

Neurasthenia in the 1980s: chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders.

In the 1980s, patients suffering from unexplained fatigue and what seemed like a prolonged attack of acute mononucleosis were given the diagnosis of chronic mononucleosis or chronic infection with the Epstein-Barr virus. Although the diagnosis has great appeal, the Epstein-Barr virus does not cause the syndrome (CFS) of chronic fatigue, which has been renamed and redefined chronic fatigue syndrome to remove the inference that the virus is its cause. From a historical perspective, both syndromes represent the 1980s equivalent of neurasthenia, a disease of fatigue that influenced the development of psychiatric nosology. Because patients with depression and anxiety also have chronic fatigue and because most patients with CFS have an affective disorder, the assessment of organic causes of this syndrome requires careful psychiatric diagnosis and treatment. Defining chronic fatigue syndrome as a medical disorder may deprive patients of competent treatment of their affective disorder.

Pattern recognition analysis of in vivo enzyme-substrate fluorescence velocities in microorganism detection and identification.

A spectrometric technique is presented that combines most of the important criteria necessary for efficient detection and identification of microorganisms. These criteria include simplicity of experimental design, various degrees of sensitivity and selectivity, convenience, and total reaction times of less than 15 min. The study takes advantage of the inherent extracellular enzymes present in living as opposed to dead, non-enzyme-producing organisms. Sequentially these are harnessed in in vivo reactions with a substrate containing a select organic functional group that is known to be cleaved or hydrolyzed by a certain enzyme. The substrate is tailored so that one of the products can be induced to fluoresce, and by using a conventional spectrofluorimeter the rate at which the fluorescence appears can be recorded. By subjecting the same bacterial sample to a number of different enzyme substrates, a pattern of fluorescence response rates emerges from a 7 by 7 microorganism-substrate matrix. Detection limits ranged from 3.6 X 10(2) to 3.5 X 10(8) cells per ml for the Bacillus globigii-indoxyl acetate and Escherichia coli-diacetylfluorescein pairs, respectively. The specificity and versatility of the method for bacterial determination is demonstrated in probing different bacterial enzymes through their spectrally active metabolic products.