Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The microbial immunostimulant OK-432 has been studied intensively in preclinical systems and has shown promise as an anticancer agent in trials that have been conducted over the past 20 years in Japan. To date, no systematic dose response evaluation of this agent has defined its dose-limiting toxicity or immunobiological activity. A phase IA study has been conducted in 25 patients with metastatic cancer at the University of Pittsburgh Cancer Institute Melanoma Center, establishing 30 KE as the maximal tolerable dosage, on the basis of cutaneous reactions. Subsequently, 48 patients with resected high-risk melanoma participated in a phase IB study of OK-432. This study has evaluated the immunomodulatory activity of OK-432 at five dosages ranging from 1 KE to 20 KE, administered ID twice weekly for 3 months. A formal analysis of the treated population in comparison to the randomized control group has been conducted, and profound immunological effects have been defined in the group of patients treated with OK-432. Patients who participated in this trial had a significant depression of OK-432-inducible cytokine production (interleukin-1 beta, interferon gamma, and tumor necrosis factor alpha) at baseline. Treatment with OK-432 reversed this deficit for interferon gamma (IFN gamma) production in a dose-dependent manner, and mitigated the inhibition for interleukin-1 (IL-1) across all dosage groups. The impact of OK-432 upon other immunological functions of the treated cohorts is more variable, with durable suppression of mononuclear cell superoxide production, and in vitro cytotoxicity to tumor. Immunological characteristics of the entire cohort demonstrate a strong and significant correlation of elevated blood CD16+ cell counts and natural killer activity with early tumor progression and death due to melanoma. Favorable prognosis is associated with monocyte capacity to produce tumor necrosis factor (TNF), and polymorphonuclear leukocyte formylmethionyl-leucylphenylalanine-inducible superoxide release. This study reveals several new immunological correlates of tumor progression and lethal outcome in resected high-risk melanoma. It demonstrates that the depressed IL-1, TNF, and IFN gamma release associated with melanoma may be mitigated by treatment with OK-432. This study has defined treatment and dose response patterns of immunomodulation associated with one of the most complex immunological agents yet evaluated in phase IB trials, in a well-defined population of high-risk patients with resected melanoma.
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PMID:Phase IB trial of picibanil (OK-432) as an immunomodulator in patients with resected high-risk melanoma. 919 73

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.
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PMID:Long term recombinant interferon alpha treatment in MS with special emphasis to side effects. 934 19

Interferon alpha is currently used in chronic hepatitis and side effects are well known. They always must be kept in mind to start and to follow a patient under this therapy. A large number of autoantibodies may appear during interferon therapy, usually without clinical manifestations. The detection of dysthyroidism, requires measurement of antithyroid antibodies and TSH before and during interferon therapy. Exacerbation of chronic liver disease under IFN may be found in case of seroconversion in a patient with hepatitis B cirrhosis or in patient with a misdiagnosis of autoimmune hepatitis. Neurolopsychological disturbances are frequently reported; most of them spontaneously disappear. However, depression must be detected because of the risk of attempted or successful suicide. Worsening or sudden onset of psoriasis or lichen planus have been reported in patients treated with interferon. Appearance or aggravation of some clinical symptoms and biochemical tests may threaten life's patient under IFN therapy. The decision to maintain or to interrupt therapy should take into account the response to interferon and the severity of side effect.
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PMID:Practical management of patients treated with alpha interferon. 939 77

Studies of interferon-alpha (IFN-alpha) therapy for chronic hepatitis C have focused on viral clearance; however, few have evaluated patient's health-related quality of life during therapy. This study evaluates health-related quality of life and the prevalence of anxiety and depression in patients with chronic hepatitis C before, during, and following IFN-alpha therapy. Patients undergoing IFN-alpha therapy for chronic hepatitis C were asked to complete health status measures as well as anxiety and depression inventories before, during, and following IFN-alpha therapy. These measures were compared to the results of healthy adults in the general US population. Thirty-eight of forty-eight eligible patients (79%) with chronic hepatitis C completed the questionnaires. Respondents demonstrated a significant increase in depression during the sixth month of interferon therapy in comparison to pretreatment results. Anxiety scores improved significantly after one month of IFN-alpha in comparison to pretreatment results. Scores on the health status measures did not vary with IFN-alpha therapy. Patient responses were analyzed with respect to biochemical response (normalized transaminases) to IFN-alpha. IFN-alpha responders, who were aware of their transaminase results, exhibited lower scores on anxiety subscales during and after therapy (P = 0.02-0.04). Scores on the health status subscale, role emotional, improved in IFN-alpha responders compared to nonresponders during the sixth month of therapy (P = 0.02). Response to IFN-alpha therapy was not associated with any other differences on subscale analysis. Patients with chronic hepatitis C exhibited health perceptions similar to the general US population, and these were unchanged during IFN-alpha therapy. However, the incidence of depression significantly increased during the sixth month of IFN-alpha therapy. IFN-alpha responders exhibited fewer emotional problems as well as a lower incidence of anxiety during and following therapy.
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PMID:Effect of interferon-alpha treatment of chronic hepatitis C on health-related quality of life. 944 Jun 24

The article consists in a brief review of pre-treatment evaluation and antiviral treatment of chronic hepatitis C (HCV) infection. Patients with viraemia (i.e. HCV RNA seropositive with the PCR technique) should be evaluated historically if they lack contraindications for interferon alpha (IFN-alpha) treatment. Patients with depression, autoimmune and thyroid disorders, decompensated cirrhosis, or solid organ transplants, are ineligible for-IFN-alpha treatment. If the histological evaluation shows moderate to severe chronic hepatitis, and the HCV RNA level is < 3 million Eq/mL serum as measured by bDNA, naive (i.e. formerly untreated) patients should be given an initial 12-week course of IFN-alpha to evaluate treatment response. Those who become HCV-negative should continue the treatment for 48 weeks to increase the likelihood of sustained virological response after treatment cessation. Treatment should be discontinued in the case of patients still HCV-positive at 12 weeks, as the chances of obtaining sustained response are remote. Patients with higher pre-treatment HCV RNA levels (> or = 3 million Eq/mL) and patients manifesting unsustained response to earlier IFN treatment should receive combination treatment with ribavirin and IFN-alpha, as treatment with IFN alone is associated with poor chances of sustained response. This treatment approach is associated with an estimated sustained response rate in naive patients of 40-50 per cent.
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PMID:[Treatment response in chronic hepatitis C. Content of virus in serum is decisive for the outcome]. 945 44

Traditionally, both stress and depression have been associated with impaired immune function and increased susceptibility to infectious and neoplastic disease. However over the last number of years a large body of evidence suggests that major depression is associated with signs of immunological activation. Moreover it has been suggested that cytokine hypersecretion may be involved in the aetiology of depressive disorders. The present article reviews the evidence from both clinical and experimental studies which implicates immunological activation and particularly hypersecretion of cytokines in the onset and maintenance of depressive illness. Both clinical and experimental studies indicate that stress and depression are associated with increased circulating concentrations of cytokines such as IL-1beta, IL-6 and gamma-IFN and positive acute phase proteins, and hyperactivity of the HPA-axis. In addition, it has been reported that immunological activation induces "stress-like" behavioural and neurochemical changes in laboratory animals. Although for many years it has been suggested that stress acts a predisposing factor to depressive illness, the precise mechanisms by which stress-induced depressive symptoms occur are not fully understood. Nevertheless, behavioural changes due to stress have often been explained in terms of changes in neurotransmitter function in the brain. In the present article increased cytokine secretion is implicated as a mechanism whereby stress can induce depression.
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PMID:Depression, stress and immunological activation: the role of cytokines in depressive disorders. 947 19

Two forms of recombinant interferon-alpha (IFN-alpha2a and IFN-alpha2b) have been approved by the Food and Drug Administration for a variety of clinical indications, including hairy cell leukemia, hepatitis, acquired immunodeficiency syndrome-related Kaposi's sarcoma, chronic myelogenous leukemia (IFN-alpha2a only), and adjuvant therapy for melanoma (IFN-alpha2b only), based on their proven clinical efficacy and acceptable safety profiles. The continued postmarketing monitoring of adverse reactions associated with IFN-alpha therapy has revealed some new toxicities. The most common adverse events associated with IFN-alpha therapy are flu-like symptoms, fatigue, anorexia, and central nervous system and psychiatric reactions. In particular, the incidence of depression has only recently been fully appreciated. Some of these side effects, particularly chronic fatigue, anorexia, and neuropsychiatric reactions, may become dose limiting. New approaches to minimize and manage the side effects of IFN-alpha therapy are needed.
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PMID:Safety profile of interferon-alpha therapy. 948 35

Cytokines such as interferon-alpha (IFN-alpha) are increasingly being exploited as biologic response modifiers to treat cancer. However, treatment with IFN-alpha can adversely affect mood and cognition, causing depression, memory disturbances, and other signs of central nervous system (CNS) dysfunction. The genes encoding cytokines and their receptors are expressed in the CNS under both resting and stimulated conditions, and cytokines can affect key brain functions. The physiologic effects of IFN-alpha therapy on the CNS are probably a consequence of the activation of a complex cascade of secondary cytokines both in the periphery and within the CNS. We review the neurobiology of cytokines and outline some of the potential mechanisms by which alterations of cytokine expression in the CNS could contribute to cognitive dysfunction and mood disorders during IFN-alpha therapy.
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PMID:Cytokines and brain function: relevance to interferon-alpha-induced mood and cognitive changes. 948 38

The central nervous system side effects associated with interferon-alpha (IFN-alpha) therapy, including depression and cognitive changes, can compromise otherwise effective immunotherapy. The term "depression" has multiple meanings ranging from a feeling of sadness to a neuropsychiatric disorder with defined diagnostic criteria. A syndrome of mood disturbance with memory impairment, cognitive slowing, and impaired executive function is common with IFN-alpha therapy and is consistent with mild subcortical dementia. Cognitive deficits and mood disorder may occur independently, and in some cases depression is a reactive phenomenon. Risk factors for development of IFN-alpha neurotoxicity include duration of treatment, high-dose therapy, and prior cranial irradiation or neurologic illness. Past or current psychiatric illness also may put the patient at risk. Subtypes of major depression are associated with neuroendocrine and neurochemical alterations that are consistent with the observed activities of IFN-alpha. This may provide insight into the etiology of IFN-alpha neurotoxicity, as well as possible interventions. Assessment of the neuropsychiatric status of patients treated with IFN-alpha should be a standard of care. Possible pharmacologic interventions to decrease the neurotoxicity associated with IFN-alpha therapy include antidepressants, psychostimulants, and opioid antagonists. Preliminary clinical and research experience suggests that it is possible to effectively palliate IFN-alpha toxicity.
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PMID:Mood and cognitive side effects of interferon-alpha therapy. 948 39

Interferon-alpha (IFN-alpha) therapy is frequently associated with significant fatigue, which is often the dominant dose-limiting side effect. The fatigue associated with IFN-alpha therapy is usually dose related, worsens with continued therapy, and is associated with significant depression. Although the direct cause of IFN-alpha-induced fatigue is unknown, it is possible that neuromuscular fatigue, similar to that observed in patients with postpolio syndrome, is one component of this syndrome. The induction of proinflammatory cytokines observed in patients treated with IFN-alpha is consistent with a possible mechanism of neuromuscular pathology that could manifest as fatigue. Further research using established techniques for the study of neuromuscular fatigue is needed to test this hypothesis. Understanding the etiology of IFN-alpha-induced fatigue is the first step toward developing effective therapeutic interventions. Nonpharmacologic interventions for fatigue have begun to be seriously evaluated in cancer patients and patients receiving IFN-alpha therapy. Pharmacologic interventions for neuromuscular fatigue also are being investigated.
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PMID:Fatigue: definitions, mechanisms, and paradigms for study. 948 40


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