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Effects of stress on tumor metastasis and response to cyclophosphamide
Abstracts from C-L Forum
The Diagnosis
and Treatment
Kathleen France, Marijo Tamburrino,
of Idiopathic Edema on the C-L Service Nancy Campbell, ]udy Pent-z, Cynthia Evans,
Medical College of Ohio, Toledo, OH Idiopathic edema is a pathological state of fluid retention lacking evidence for cardiac, renal, hepatic, or allergic disease. It is more often identified in females of reproductive age. Some authors have associated the onset with psychic stress or psychotropic medications. Both patients who abuse diuretics, thereby producing secondary hyperaldosteronism, and the idiopathic edematous patient describe complicated and confusing symptoms. Psychiatric consultants may be requested to evaluate these patients and assist in their management. The reestablishment of normal dopaminergic activity reduces symptoms when diuretics are of no avail. A case will be presented to demonstrate current theoretical understanding of the disorder and treatment approaches.
Psychological Undergoing
and Immunological
Reactions of Family Members to Patients
Bone Marrow Transplantation
Ann D. Futterman,
David K. Wellisch, Jacob Zighelboim,
Herbert Weiner
UCLA School of Medicine, Departments of Psychiatry and Medicine, Los Angeles, CA Both patients and family members must endure a great deal of psychological distress during bone marrow transplantation (BMT) procedures. To date, 16 family members (either spouses or parents) of patients undergoing BMT procedures at UCLA have been evaluated immunologically and psychologically over the course of BMT. Blood is drawn and psychological questionnaires are obtained from family members immediately prior to the patient’s BMT, when the patient enters protective isolation, when the patient leaves isolation or has Do Not Resuscitate (DNR) status enacted, and when the patient leaves the hospital. Although results are preliminary, there appear to be significant and progressive declines in natural killer cell activity, response to anti-T3 cells, CD8 suppressoricytotoxic T cell numbers, and lymphocytosis in many of the family members over the course of the transplant. Many subjects experience a decline in optimism and positive affect and an increase in negative affect over the course of the transplant. Subjects appear to receive the majority of their support from nursing staff and others on the BMT service, and family members. Notable immunological changes have been identified in some subjects immediately after stressful events occurred during the transplant.
Effects of Stress on Tumor Metastasis and Response to Cyclophosphamide T. Giraldi, L. Perissin, S. Zorzet, V. Rapozzi, M.G. Rodani lstituto di Biologia,
Facolta di Medicina,
Universita di Udine 33100-Udine,
Italy
A relatively large number of reports exist in the literature showing that stress can influence the incidence and progression of tumors in laboratory animals, but little attention has been given to the problem of metastasis formation. The aim of the present work has thus been to determine the effects of applying defined paradigms of psychological stress to mice kept in a low-stress environment on primary tumor growth and spontaneous metastasis of Lewis lung carcinoma. The stressors examined are the anticipatory anxiety caused by the periodic application of spatial disorientation (SD), early maternal deprivation, behavioral despair, physical restraint, and avoidable versus unavoidable footshock in conditioned animals. SD reproducibly causes a significant and marked increase in metastasis weight independent from primary tumor, whose magnitude varies with a circannual rhythm; marginal and scarcely reproducible results have been obtained with the other experimental paradigms used. The nature of the mediators operative in the effects of SD have been examined by direct hormonal assay, and by treatment of the animals with pharmacological inhibitors or antagonists of specific neuroendocrine effecters. In these conditions, the participation of plasmatic glucocorticoids appears to be insignificant, that of P-endorphin and prolactin are significant, whereas the adrenergic system appears principally involved. An increase in the urinary excretion of melatonin is observed upon application of SD, which accompanies the observed increase in lung metastasis weight. The antitumor resistance factors of the host modulated by SD appear to participate in determining the action of the antitumor drug cyclophosphamide (CY), as its curative effects are abolished in mice subjected to SD. The effects 371
J. J, Strain and J. C. B. Holland
of CY have been examined also in mice subjected to other stressor paradigms (behavioral despair and physical restraint), and do not produce effects as evident and reproducible as those observed when SD is applied. These results indicate that psychological stressors can control tumor metastasis by host’s antitumor resistance factors through neuroendocrine mechanisms. These factors appear relevant for tumor spread and curability by antitumor agents, with implications of interest for experimental and clinical situations.
Premenstrual Changes and Reproductive-Related Depressions Leslie Hartley Gise, Patricia L. Puddison, Lisa Robinson, Maria Russo, Jumes J. Strain Mount Sinai School of Medicine, New York, NY Of 346 women seeking treatment for premenstrual symptoms, 48 (14%) had a premenstrual disorder prospectively confirmed using the NIMH criteria of 1983 and the Late Luteal Phase Dysphoric Disorder criteria of DSM-III-R. Using a logistic regression analysis, women with a prospectively confirmed premenstrual disorder differed from others with regard to duration of illness (p = O.Ol), past treatment for premenstrual symptoms (p < 0.05), and beliefs about their health (p < 0.05). Other demographic, clinical, and psychologic variables failed to distinguish women with a prospectively confirmed premenstrual disorder from others complaining of premenstrual symptoms. Twenty percent (69/346) had a past history of a major depressive episode following the use of oral contraceptive agents and were younger (p < .05) and more likely to have a family history of mental illness or alcoholism (p < .Ol). Twenty-two percent (76/346) had a past history of a major depressive episode postpartum and were more likely to be married (p = 0.0001) with poorer marital adjustment (p < 0.01). These data emphasize the need for prospective documentation in order to diagnose a premenstrual disorder. Although reproductive-related depressions were not uncommon among women seeking treatment for premenstrual symptoms, they did not predict a prospectively confirmed premenstrual disorder. Further study of past and family history of depression as well as marital status and marital adjustment among women with reproductive-related depressions is needed.
Efficacy of Pharmacological Treatment of Anxiety in HIV-Positive Asymptomatic Men Dun Alan Hirsch, Joanne Fishman, Paul Jacobsen, Jimmie Holland, William Breitburt Psychiatry Service, Memorial Sloan-Kettering Cancer Center, New York, NY Reactive anxiety is a profound problem for those individuals diagnosed as HIV seropositive, and conventional anxiolytic agents often produce significant adverse side effects, such as sedation. We have examined the efficacy of buspirone, in the treatment of anxiety in HIV-positive, asymptomatic gay men. Ten of a planned sample of 35 HIV-positive, asymptomatic gay men have been entered into an 8-week, doubleblind, placebo-controlled clinical trial of buspirone. The average study subject is a white, 36-year-old, exclusively homosexual male. Fifty-five percent of the sample were engaged in a full-time personal relationship and are currently employed full time. Two-thirds of the sample qualified for a DSM-III-R diagnosis of generalized anxiety disorder, and the remaining subjects received a diagnosis of an adjustment disorder with anxious or mixed features. Weekly assessments are utilized to evaluate a spectrum of psychological symptoms, compliance with medication regimen, healthrelated behaviors, and health locus of control. Due to the unique anxiolytic activity and low side-effect profile of buspirone, this medication would appear to be an ideal agent for the treatment of anxiety in HIV-seropositive individuals. Data on the efficacy of the medication in reducing psychological distress will be presented. Implications for the use of psychopharmacological intervention in thispopulation will be discussed.
372
The Diagnosis
and Treatment
Kathleen France, Marijo Tamburrino,
of Idiopathic Edema on the C-L Service Nancy Campbell, ]udy Pent-z, Cynthia Evans,
Medical College of Ohio, Toledo, OH Idiopathic edema is a pathological state of fluid retention lacking evidence for cardiac, renal, hepatic, or allergic disease. It is more often identified in females of reproductive age. Some authors have associated the onset with psychic stress or psychotropic medications. Both patients who abuse diuretics, thereby producing secondary hyperaldosteronism, and the idiopathic edematous patient describe complicated and confusing symptoms. Psychiatric consultants may be requested to evaluate these patients and assist in their management. The reestablishment of normal dopaminergic activity reduces symptoms when diuretics are of no avail. A case will be presented to demonstrate current theoretical understanding of the disorder and treatment approaches.
Psychological Undergoing
and Immunological
Reactions of Family Members to Patients
Bone Marrow Transplantation
Ann D. Futterman,
David K. Wellisch, Jacob Zighelboim,
Herbert Weiner
UCLA School of Medicine, Departments of Psychiatry and Medicine, Los Angeles, CA Both patients and family members must endure a great deal of psychological distress during bone marrow transplantation (BMT) procedures. To date, 16 family members (either spouses or parents) of patients undergoing BMT procedures at UCLA have been evaluated immunologically and psychologically over the course of BMT. Blood is drawn and psychological questionnaires are obtained from family members immediately prior to the patient’s BMT, when the patient enters protective isolation, when the patient leaves isolation or has Do Not Resuscitate (DNR) status enacted, and when the patient leaves the hospital. Although results are preliminary, there appear to be significant and progressive declines in natural killer cell activity, response to anti-T3 cells, CD8 suppressoricytotoxic T cell numbers, and lymphocytosis in many of the family members over the course of the transplant. Many subjects experience a decline in optimism and positive affect and an increase in negative affect over the course of the transplant. Subjects appear to receive the majority of their support from nursing staff and others on the BMT service, and family members. Notable immunological changes have been identified in some subjects immediately after stressful events occurred during the transplant.
Effects of Stress on Tumor Metastasis and Response to Cyclophosphamide T. Giraldi, L. Perissin, S. Zorzet, V. Rapozzi, M.G. Rodani lstituto di Biologia,
Facolta di Medicina,
Universita di Udine 33100-Udine,
Italy
A relatively large number of reports exist in the literature showing that stress can influence the incidence and progression of tumors in laboratory animals, but little attention has been given to the problem of metastasis formation. The aim of the present work has thus been to determine the effects of applying defined paradigms of psychological stress to mice kept in a low-stress environment on primary tumor growth and spontaneous metastasis of Lewis lung carcinoma. The stressors examined are the anticipatory anxiety caused by the periodic application of spatial disorientation (SD), early maternal deprivation, behavioral despair, physical restraint, and avoidable versus unavoidable footshock in conditioned animals. SD reproducibly causes a significant and marked increase in metastasis weight independent from primary tumor, whose magnitude varies with a circannual rhythm; marginal and scarcely reproducible results have been obtained with the other experimental paradigms used. The nature of the mediators operative in the effects of SD have been examined by direct hormonal assay, and by treatment of the animals with pharmacological inhibitors or antagonists of specific neuroendocrine effecters. In these conditions, the participation of plasmatic glucocorticoids appears to be insignificant, that of P-endorphin and prolactin are significant, whereas the adrenergic system appears principally involved. An increase in the urinary excretion of melatonin is observed upon application of SD, which accompanies the observed increase in lung metastasis weight. The antitumor resistance factors of the host modulated by SD appear to participate in determining the action of the antitumor drug cyclophosphamide (CY), as its curative effects are abolished in mice subjected to SD. The effects 371
J. J, Strain and J. C. B. Holland
of CY have been examined also in mice subjected to other stressor paradigms (behavioral despair and physical restraint), and do not produce effects as evident and reproducible as those observed when SD is applied. These results indicate that psychological stressors can control tumor metastasis by host’s antitumor resistance factors through neuroendocrine mechanisms. These factors appear relevant for tumor spread and curability by antitumor agents, with implications of interest for experimental and clinical situations.
Premenstrual Changes and Reproductive-Related Depressions Leslie Hartley Gise, Patricia L. Puddison, Lisa Robinson, Maria Russo, Jumes J. Strain Mount Sinai School of Medicine, New York, NY Of 346 women seeking treatment for premenstrual symptoms, 48 (14%) had a premenstrual disorder prospectively confirmed using the NIMH criteria of 1983 and the Late Luteal Phase Dysphoric Disorder criteria of DSM-III-R. Using a logistic regression analysis, women with a prospectively confirmed premenstrual disorder differed from others with regard to duration of illness (p = O.Ol), past treatment for premenstrual symptoms (p < 0.05), and beliefs about their health (p < 0.05). Other demographic, clinical, and psychologic variables failed to distinguish women with a prospectively confirmed premenstrual disorder from others complaining of premenstrual symptoms. Twenty percent (69/346) had a past history of a major depressive episode following the use of oral contraceptive agents and were younger (p < .05) and more likely to have a family history of mental illness or alcoholism (p < .Ol). Twenty-two percent (76/346) had a past history of a major depressive episode postpartum and were more likely to be married (p = 0.0001) with poorer marital adjustment (p < 0.01). These data emphasize the need for prospective documentation in order to diagnose a premenstrual disorder. Although reproductive-related depressions were not uncommon among women seeking treatment for premenstrual symptoms, they did not predict a prospectively confirmed premenstrual disorder. Further study of past and family history of depression as well as marital status and marital adjustment among women with reproductive-related depressions is needed.
Efficacy of Pharmacological Treatment of Anxiety in HIV-Positive Asymptomatic Men Dun Alan Hirsch, Joanne Fishman, Paul Jacobsen, Jimmie Holland, William Breitburt Psychiatry Service, Memorial Sloan-Kettering Cancer Center, New York, NY Reactive anxiety is a profound problem for those individuals diagnosed as HIV seropositive, and conventional anxiolytic agents often produce significant adverse side effects, such as sedation. We have examined the efficacy of buspirone, in the treatment of anxiety in HIV-positive, asymptomatic gay men. Ten of a planned sample of 35 HIV-positive, asymptomatic gay men have been entered into an 8-week, doubleblind, placebo-controlled clinical trial of buspirone. The average study subject is a white, 36-year-old, exclusively homosexual male. Fifty-five percent of the sample were engaged in a full-time personal relationship and are currently employed full time. Two-thirds of the sample qualified for a DSM-III-R diagnosis of generalized anxiety disorder, and the remaining subjects received a diagnosis of an adjustment disorder with anxious or mixed features. Weekly assessments are utilized to evaluate a spectrum of psychological symptoms, compliance with medication regimen, healthrelated behaviors, and health locus of control. Due to the unique anxiolytic activity and low side-effect profile of buspirone, this medication would appear to be an ideal agent for the treatment of anxiety in HIV-seropositive individuals. Data on the efficacy of the medication in reducing psychological distress will be presented. Implications for the use of psychopharmacological intervention in thispopulation will be discussed.
372