Biomedical subjects

D F Darko

Publications and source records attributed to D F Darko.

At least 19 recordsLinked to original sources

PubMed1998

Growth hormone, fatigue, poor sleep, and disability in HIV infection.

Poor sleep, daytime fatigue, and loss of cognitive ability exist during all stages of HIV infection, worsening with disease progression. These symptoms contribute to disability and poor quality of life. Data from several research groups support a role of somnogenic inflammatory process peptides elevated in HIV infection, e.g. TNF alpha. Though the literature is in conflict regarding an effect of HIV infection on growth hormone (GH) secretion, GH axis dysregulation and treatment with GH may be important in HIV infection, e.g. in the wasting syndrome. It has long been known that GH varies with changes in sleep. The hypothesis tested in the current study was that the relationship between delta frequency (0.5-4.0 Hz) sleep EEG amplitude (square root of power from frequency analysis) and GH secretion would differ between HIV positive (HIV+) and HIV negative (HIV-) subjects. In 14 subjects (6 HIV+ and 8 HIV-, none with current or past AIDS-defining illness) a linear relationship change across the night's sleep was found in the coupling between delta frequency sleep EEG amplitude and GH secretion. The phase coupling change was in opposite directions in HIV+ versus HIV- subjects. This difference supports the hypothesis that the brain-based coordination of sleep and sleep-related physiology deteriorates early in HIV infection, and that GH dysregulation may contribute to this sleep pathology.

Adult↗

PubMed1995

Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection.

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.

Adult↗

PubMed1995

Lentiviral infection, immune response peptides and sleep.

The aberrant sleep documented in subjects with human immunodeficiency virus (HIV) infection is uniquely important because of the contribution this poor quality sleep makes to the fatigue, disability, and eventual unemployment that befalls these patients. Especially given this importance in clinical care, the research on the prominent sleep changes described in HIV infection remains modest in quantity. The chronic asymptomatic stage of HIV infection is associated with the most intriguing and singular sleep structure changes. Especially robust is the increase in slow wave sleep, particularly in latter portions of the sleep period. This finding is rare in other primary or secondary sleep disorders. The sleep structure alterations are among the most replicable of several pathophysiological sequelae in the brain associated with early HIV infection. It is unlikely that these sleep architecture changes are psychosocial in etiology, and they occur before medical pathology is evident. They are not associated with stress, anxiety, or depression. Evidence is accumulating to support a role for the somnogenic immune peptides tumor necrosis factor (TNF)alpha and interleukin (IL-1 beta) in the sleep changes and fatigue commonly seen in HIV infection. These peptides are elevated in the blood of HIV-infected individuals, and are somnogenic in clinical use and animal models. The peripheral production of these peptides may also have a role in the regulation of normal sleep physiology. The lentivirus family contains both HIV and the feline immunodeficiency virus (FIV). The use of the FIV model of HIV infection may provide a way to further investigate the mechanism of a neurotropic, neurotoxic virus initiating the immune acute phase response and affecting sleep. Neurotropic lentivirus infection is a microbiological probe facilitating neuroimmune investigation.

AIDS Dementia Complex↗

PubMed1995

Early central nervous system response to HIV infection: sleep distortion and cognitive-motor decrements.

OBJECTIVE: To repeat and extend findings suggesting that sleep disturbance, excessive daytime sleepiness, and degraded cognitive-motor abilities may be early markers of central nervous system (CNS) involvement in HIV infection. DESIGN: A controlled, cross-sectional, prospective analysis. SETTING: Clinical research center at a teaching hospital and a military health research center. SUBJECTS: Twenty-three HIV-positive (mean CD4+ count, 387 +/- 162 x 10(6)/l) and 13 seronegative men who were Naval personnel or participants of the University of California, San Diego HIV Neurobehavioral Research Center. MAIN OUTCOME MEASURES: Nocturnal and daytime sleep electroencephalogram, electromyogram, and electrocardiogram. Simple and complex cognitive-motor performance assessed via computerized tasks. RESULTS: Comparison of sleep parameters based on HIV status, length of time infected, zidovudine use, and CD4+ count indicated that CD4+ T cells > 400 x 10(6)/l were associated with a distortion in nocturnal sleep characterized by increased stages 3 and 4 non-rapid eye movement (i.e., slow-wave) sleep in the latter portion of the night and reduced nocturnal awakenings. HIV-positive patients were no sleepier in the daytime than controls. Cognitive-motor performance revealed deficits in both accuracy and efficiency for HIV-positive patients. CONCLUSION: Asymptomatic HIV-positive patients with CD4+ counts > 400 x 10(6)/l demonstrate a statistically significant increase in slow-wave sleep during the latter portion of the night and less arousability. CD4+ lymphocyte count in the early phases of HIV infection appears to differentiate between various levels of HIV disease progression with respect to certain CNS measurements of nocturnal sleep and cognitive-motor performance. Sleep structure distortion remains one of the earliest and most consistently replicable physiological signs of HIV infection. This distortion may provide a link to immune function, disease progression, and cognitive-motor disability in HIV infection.

AIDS Dementia Complex↗

PubMed1994

Bereavement, depression, and immune function.

This study evaluates whether recently widowed women who fulfill criteria for a depressive syndrome differ in their immune responses from widows who do not. Twenty-one middle-aged widows who had lost their spouses 2 months before the initial evaluation and 21 demographically matched married women were evaluated at approximately 6-month intervals for 13 months. Evaluations consisted of diagnostic interviews using the Schedule for Affective Disorders and Schizophrenia, Hamilton Rating Scale for Depression, and Beck Depression Inventory. Immune function was measured by total lymphocyte counts, natural killer (NK) cell activity, mitogen responsiveness to concanavalin A, and T-cell subsets. There were no statistically significant differences on any of the immune measures between the entire cohort of widows and control subjects. However, the subset of widows who met DSM-III-R criteria for major depressive syndromes demonstrated impaired immune function (lower NK cell activity and lower mitogen stimulation) compared with those who did not meet criteria for major depression. This study suggests a relationship between impaired immune function and depression in women experiencing the stress of bereavement.

Aged↗

PubMed1992

Plasma beta-endorphin and natural killer cell activity in major depression: a preliminary study.

Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta-endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04), but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group.

Adult↗

PubMed1992

Fatigue, sleep disturbance, disability, and indices of progression of HIV infection.

OBJECTIVE: The authors' objective was to test the hypothesis that fatigue affects the activities and employment of subjects with HIV infection and that indices of immunosuppression and inflammation may have statistical utility in predicting fatigue and sleep disturbance. METHOD: The authors prospectively asked 112 homosexual men (62 HIV-seropositive subjects and 50 HIV-seronegative comparison subjects) to complete a questionnaire on fatigue and sleep disturbance. In addition, hematocrit, WBC count, CD4+ cell number, lactate dehydrogenase, albumin, and total globulin were measured. RESULTS: For HIV-seropositive patients fatigue was significantly more of a problem and interfered more with important activities such as employment and driving than with seronegative comparison subjects. The HIV-infected patients were significantly more likely to be unemployed, to feel fatigued through more hours of the day, to sleep more, to nap more, and to have diminished midmorning alertness. The medical variables could be used to statistically predict fatigue, its interference with daily activities, and employment. CONCLUSIONS: Fatigue and sleep disturbances contribute to morbidity and disability in HIV-infected homosexual men, especially those in CDC stage IV (AIDS-related complex or AIDS). Correlation with measures of immunosuppression and inflammation and comparison between fatigued versus nonfatigued groups suggest the possibility of statistical prediction of fatigue by using these measures. Further study is needed to examine the possibility of eventual specific intervention to clinically treat HIV-related fatigue, sleepiness, and sleep disturbance.

AIDS-Related Complex↗

PubMed1992

Association of beta-endorphin with specific clinical symptoms of depression.

OBJECTIVE: Abnormalities in plasma concentrations of beta-endorphin-like immunoreactivity (beta-endorphin) have been reported in depressed patients. This study was done to test the hypothesis that specific clinical characteristics of depression are associated with plasma beta-endorphin concentration. METHOD: Plasma beta-endorphin was evaluated in 20 depressed patients diagnosed according to DSM-III-R and in 23 age- and sex-matched comparison subjects, and each was evaluated with the structured Schedule for Affective Disorders and Schizophrenia (SADS). Twelve SADS items involving dysphoric mood and related symptoms were chosen for analysis. RESULTS: Within the group of all 43 subjects and within the depressed group, beta-endorphin level correlated significantly with psychic anxiety and with phobia. In the depressed group only, beta-endorphin also correlated significantly with obsessions/compulsions. Concentration of beta-endorphin was not significantly correlated with score on the Hamilton Rating Scale for Depression or Beck Depression Inventory or with scores on other SADS symptom items, including somatic anxiety, insomnia, subjective anger, overt anger, agitation, psychomotor retardation, panic attacks, appetite loss, or total weight loss. In the group of 23 comparison subjects, beta-endorphin did not correlate with Beck or Hamilton depression score or with any of the SADS clinical variables. CONCLUSIONS: High levels of plasma beta-endorphin may be associated with more severe anxiety, phobia, and obsessions/compulsions in depressed patients.

Adult↗

PubMed1991

A critical appraisal of mitogen-induced lymphocyte proliferation in depressed patients.

OBJECTIVE: The authors' goal was to evaluate the utility of mitogen-induced lymphocyte proliferation assays in clinical research in psychoimmunology. METHOD: They examined 23 depressed patients and 23 matched comparison subjects with this assay. There were no significant differences between these groups. They then combined the results of this study with the results of their previous study of 20 depressed patients and 20 comparison subjects to examine possible determinants of lymphocyte proliferation in depression. RESULTS: Depressed patients with lower proliferative responses than their matched comparison subjects had lower depression subscale, anergia subscale, and total scores on the Brief Psychiatric Rating Scale than did patients with higher proliferative responses than their matched comparison subjects. This finding was unexpected and unexplained. Depressed patients with lower proliferative responses than their matched comparison subjects also had fewer obsessions and compulsions and less psychomotor agitation according to the Schedule for Affective Disorders and Schizophrenia interview than did patients with higher proliferative responses than their matched comparison subjects. Stepwise discriminant analysis and cluster analysis contributed little further understanding of the determinants of in vitro lymphocyte proliferation of cells from depressed patients. CONCLUSIONS: Longitudinal studies using multiple serial determinations of mitogen-induced lymphocyte proliferation are the minimal design needed to make this assay useful in further evaluating any immune system changes in depression.

Adult↗

PubMed1990

Antidepressant treatment and the occurrence of mania in bipolar patients admitted for depression.

We examined the records of 33 patients who had 70 inpatient admissions with a diagnosis of bipolar affective disorder, depressed. During 14 of these admissions, a switch occurred from depression into mania. We compared the treatment patients were on at the time of their switch to treatment during the 56 admissions where there was no switch. We conclude that clinicians must be prepared for depressed bipolar patients to switch to mania regardless of treatment status.

Antidepressive Agents, Tricyclic↗

PubMed1989

Mitogen-stimulated lymphocyte proliferation and pituitary hormones in major depression.

To assess cellular immune status and the hypothalamic-pituitary (HP) axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma levels of cortisol, adrenocorticotropin hormone (ACTH), growth hormone (GH), and prolactin (PRL). Twenty patients with major depression were compared with 20 control subjects matched for age, sex, and race. The dose-response curves for concanavalin-A (Con-A) and phytohemagglutinin (PHA) stimulation were not significantly different between the two groups. The patients had decreased Con-A-stimulated T-lymphocyte proliferation when compared to the control subjects, but only at the lowest suboptimal concentration of Con-A. None of the four concentrations of PHA-stimulated proliferation were different between the two groups, neither was PHA-induced interleukin-2 production. Within the patient group only, plasma prolactin (PRL) correlated significantly with stimulated lymphocyte proliferation using two optimal concentrations of PHA and one optimal concentration of Con-A, when the proliferation was expressed using the stimulation index.

Adrenocorticotropic Hormone↗

PubMed1989

Peripheral white blood cells and HPA axis neurohormones in major depression.

Alterations in peripheral blood leukocyte distribution in major depression, including leukocytosis, neurotrophilia and lymphopenia, have been described. To assess peripheral white blood cells and the hypothalamic-pituitary (HP) axis in drug-free patients with major depression, we measured the total white blood cell count (WBC), and percentage of lymphocytes, and the plasma levels of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH) and prolactin (PRL). Twenty male patients with major depression had relative lymphopenia and leukocytosis when compared with 20 age, sex and racematched control subjects. Elevated Beck and Hamilton depression scores correlated with a decreased percentage of lymphocytes, in a group of all subjects combined. There was a weak tendency for elevated growth hormone to correlate with relative lymphopenia in the control subjects only. Relative lymphopenia and leukocytosis may be a part of the psychobiology of major depression.

Adrenocorticotropic Hormone↗

PubMed1988

Immune cells and the hypothalamic-pituitary axis in major depression.

To explore changes in immune cell status with changes in the hypothalamic-pituitary (HP) axis in 20 patients with major depression as compared with 20 age-, sex-, and race-matched control subjects, we examined peripheral blood mononuclear cells (PBMC) for total T-cells (T3), total B-cells (B1), two T-cell subsets (T4 and T8), and natural killer cells (NKH1), and we measured the plasma level of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL). The ratio of T4/T8 was increased in the patients. Within the group of control subjects only, increasing age correlated significantly with decreasing plasma PRL. Within the group of patients only, GH positively correlated significantly with T8 and NKH1, as did PRL with NKH1. No between-groups difference was found for T3, B1, T4, T8, NKH1, cortisol, ACTH, GH, or PRL.

Adult↗

PubMed1988

Neutrophilia and lymphopenia in major mood disorders.

Alterations in peripheral blood leukocyte distribution in major depression, including lymphopenia, neutrophilia, eosinopenia, and monocytopenia, have been described. The present study was designed to replicate these results, but with methodological improvements, including age-, sex-, and race-matched control subjects; DSM-III and Research Diagnostic Criteria diagnoses based on the Schedule for Affective Disorders and Schizophrenia interview; objective and subjective severity of depression measured quantitatively; and consideration of psychosocial stressors (DSM-III, Axis IV). We found relative lymphopenia and absolute neutrophilia and leukocytosis in depression, but did not find decreased numbers of eosinophils or monocytes. The relative lymphopenia and absolute neutrophilia were present in the subgroup of only unipolar depressed patients, but not in the bipolar, currently depressed subgroup. However, these blood cell changes were not found in a subgroup of patients who had been medication free greater than or equal to 1 month but only in the subgroup of patients using medication at the time of phlebotomy. Groups formed on the basis of psychosocial stress levels were not found to have significant significant intergroup differences in white blood cell (WBC) counts. The clinical significance of these findings needs study. While leukocytosis and neutrophilia can be found in major depression, these changes are perhaps secondary to medication use.

Adult↗

PubMed1988

Cellular immunity and the hypothalamic-pituitary axis in major affective disorder: a preliminary study.

To assess cellular immune status and the hypothalamic-pituitary axis in patients with major depression, we examined peripheral blood mononuclear cells and measured the plasma levels of four neurohormones. Eleven patients with major depression had increased % of T4 lymphocytes and decreased concanavalin (Con A) stimulated T lymphocyte proliferation when compared with 11 age-, sex-, and race-matched control subjects. Percent of total lymphocytes labeled as all T lymphocytes, all B lymphocytes, and natural killer cells did not differ in the two groups, nor did mitogen-induced interleukin-2 production. These findings support theories of interaction between depression and immune cell function.

Adrenocorticotropic Hormone↗

PubMed1988

Age, cellular immunity and the HP axis in major depression.

1. To assess the effect of age on cellular immune status and the HP axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma level of four neurohormones. 2. In 36 subjects, decreasing T lymphocyte response to con A covaried with age. Percent of lymphocytes labeled as T8 lymphocytes tended to decrease and T4/T8 ratio tended to increase with increasing age. 3. Hamilton and Beck scores were significantly different between the two sex and race matched groups of 18 depressed patients and 18 control subjects, and plasma prolactin was significantly higher in depressed subjects. 4. Increasing age correlated with decreasing T lymphocyte response to con A in the combined group of all subjects, and in the control group, but not in the patient group. 5. Hamilton and Beck scores correlated inversely with T lymphocytes response in the combined group of all subjects. 6. Differences in mitogen responsiveness between patient and control groups were not found, having been obscured by the effect of age. 7. These findings indicate the need to age match subjects when studying the interaction between depression and immune cell function.

Adult↗

PubMed1988

The diagnostic dilemma of myxedema and madness, axis I and axis II: a longitudinal case report.

A patient with presumed chronic paranoid schizophrenia had chronic thyroiditis and Grade I hypothyroidism. Psychosis cleared following treatment with thyroid replacement. The probable presence of two axis II disorders may have contributed to the missed medical diagnosis and the patient's eventual suicide. The personality disorders were a major problem in the patient's medical and psychiatric care. The differential diagnosis among hypothyroidism and primary axis I psychotic and depressive psychopathology has always been problematic. When axis II pathology is also present, the diagnostic dilemma is increased.

Adult↗

PubMed1987

Folie à famille: shared paranoid disorder in a Vietnam veteran and his family.

Reports of folie à famille are rare; this may be the first reported case involving a Vietnam veteran. Expression of his paranoid schizophrenia involved delusions and hallucinations relating to Vietnam, and his wife and children shared his paranoia. Typical of folie à famille were the dominant family member, the threat of violence, and the family's social isolation, frequent crises, and stable membership. Although the veteran's intrusive recollections of his Vietnam experience were typical of posttraumatic stress disorder, he acted on rather than avoided them. Treatment focused on the entire family, partly to minimize future problems in the children.

Adolescent↗