PubMed Health⌕ Search

Biomedical subjects

M N Starkman

Publications and source records attributed to M N Starkman.

At least 19 recordsLinked to original sources
PubMed2001

Overexpression of CXC chemokines by an adrenocortical carcinoma: a novel clinical syndrome.

A patient with adrenocortical carcinoma presented with fever, leukocytosis, and increased acute phase reactants. The tumor was infiltrated with neutrophils. Immunohistochemical staining of the tumor showed positive signal for epithelial neutrophil-activating protein-78, an angiogenic and chemotactic CXC chemokine. Conditioned medium from tumor-derived cells (RL-251) showed high concentration of IL-8, epithelial neutrophil-activating protein-78, Gro alpha, and Gro gamma, angiogenic CXC chemokines with a potential role in tumorigenesis. An adrenal cancer/severe combined immunodeficiency mouse chimera was developed. Mice grew tumors rapidly, and circulating levels of IL-8 and epithelial neutrophil-activating protein-78 were detected. In contrast, animals transplanted with NCI-H295 cells, a nonchemokine-secreting cell line, grew tumors more slowly and did not have detectable chemokine levels. Similar to the patient, mice with RL-251 tumors developed marked leukocytosis and neutrophilia, and their tumors were infiltrated with neutrophils. Mice were passively immunized with epithelial neutrophil-activating protein-78 antisera. A marked decrease in tumor growth was observed. Potential for chemokine production by other adrenocortical tumors was investigated by RT-PCR in archival material. Six of seven adrenal carcinomas and one of three adenomas had cDNA for IL-8; six of seven carcinomas and the three adenomas had cDNA for epithelial neutrophil-activating protein-78. We concluded that the clinical presentation of this case resulted from increased tumor production of chemotactic chemokines. Through their angiogenic and chemotactic properties these chemokines may play an important role in adrenal tumorigenesis.

17-Hydroxycorticosteroids↗
PubMed1999

Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

BACKGROUND: Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy. METHODS: The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment. RESULTS: Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease. CONCLUSIONS: Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.

Adult↗
PubMed1994

Diurnal rhythm of plasma delta-sleep-inducing peptide in humans: evidence for positive correlation with body temperature and negative correlation with rapid eye movement and slow wave sleep.

Since delta-sleep-inducing peptide (DSIP) was isolated in 1977, numerous reports have suggested that this nonapeptide stimulates delta-sleep [slow wave sleep (SWS)]. Although DSIP-like immunoreactivity (DSIP-LI) has been found in the serum of many animals and man, its diurnal rhythm and relation to sleep stages have not been well defined. We hypothesized that circulating levels of this putative sleep hormone would be highest at night and would probably be elevated before or during episodes of SWS. We, therefore, measured plasma DSIP-LI levels every 30 min for 24 h in 12 normal volunteers in whom we obtained simultaneous polygraphic recordings. We found a distinct diurnal rhythm for plasma DSIP-LI levels, with the maximum at 1500 h and the minimum at 0100 h. DSIP-LI levels were substantially lower in rapid eye movement sleep (P < 0.005) and somewhat lower in SWS (P < 0.05) compared to awake values. DSIP-LI levels did not rise before, during, or after a significant percentage of episodes of SWS. We found, however, that the diurnal rhythm of DSIP-LI closely followed that of body temperature with a high degree of correlation (r2 = 0.66; P < 0.0001). We conclude that endogenous elevations of circulating DSIP may be associated with suppression of slow wave and rapid eye movement sleep, and that the circadian rhythm of this peptide is coupled directly or indirectly to that of body temperature.

Adrenocorticotropic Hormone↗
PubMed1992

Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome.

Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum, correcting for total intracranial volume. For 27% of the patients, HF volume fell outside the 95% confidence intervals for normal subject volume given in the literature. In addition, there were significant and specific correlations between HF volume and scores for verbal paired associate learning, verbal recall, and verbal recall corrected for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association between reduced HF volume, memory dysfunction, and elevated cortisol in patients with CS.

Adolescent↗
PubMed1992

EEG sleep in Cushing's disease and Cushing's syndrome: comparison with patients with major depressive disorder.

Because patients with Cushing' syndrome (CS) and Major depressive disorder (MDD) share features of hypercortisolism and the depressive syndrome, we compared electro-encephalographic (EEG) sleep in patients with pituitary-ACTH-dependent Cushing's syndrome (Cushing's disease, CD), patients with ACTH-independent Cushing's syndrome (AICS), patients with major depressive disorder (MDD), and normal subjects. There were substantial similarities in the abnormal polysomnography profiles of patients with CD, AICS, and MDD. All three patient groups demonstrated poorer sleep continuity, shortened rapid eye movement (REM) latency, and increased first REM period density compared with normal subjects. In addition, AICS patients and MDD patients had elevated REM activity and density. These findings are discussed in terms of models of pathophysiology that relate abnormalities in sleep, mood, and hypothalamic-pituitary-adrenal function.

Adenoma↗
PubMed1992

Discordant changes in plasma ACTH and beta-lipotropin/beta-endorphin levels in Cushing's disease patients with depression.

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Sleep architecture and sleep apnea in patients with Cushing's disease.

Patients with Cushing's syndrome (CS) frequently have sleep complaints. We evaluated sleep polysomnographically in 22 patients, including 17 with pituitary-ACTH-dependent Cushing's disease (CD) and five with CS from an adrenal tumor. Data were compared to healthy controls of comparable age. Seven patients (32%) demonstrated at least mild sleep apnea (> or = 9.4 events/hour), and four of 22 (18%) had > or = 17.5 events/hour. The apneic CD and CS patients had a trend for a greater complaint of excessive daytime sleepiness. Both apneic and nonapneic groups had considerable snoring and obesity. The electroencephalographic (EEG) sleep of nonapneic patients was compared to that of normal subjects. Nonapneic CD patients differed strikingly from healthy volunteers in sleep continuity and architecture, demonstrating lighter, fragmented sleep. Rapid eye movement (REM) sleep in CD patients bore many similarities to the sleep of patients with major depression, with REM latency being significantly shortened and REM density significantly increased. Continued examination of EEG sleep in CD patients may shed light on similarities in pathophysiology between CD and major depression, disorders which are characterized by both a dysfunction of the hypothalamic-pituitary-adrenal axis and alterations in mood.

ACTH Syndrome, Ectopic↗
PubMed1986

Cushing's syndrome after treatment: changes in cortisol and ACTH levels, and amelioration of the depressive syndrome.

Twenty-three patients with pituitary adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome were studied before and after treatment. The relationship between the amelioration of the depressive syndrome and changes in cortisol and ACTH levels was investigated. There was a significant difference in mean change in 24-hour urinary free cortisol (UFC) excretion for changes in the depressed mood score from first to last visit. There were also significant correlations between decreases in UFC and decreases in both the depressed mood score and the modified Hamilton depression score. These relationships were not found for ACTH. Furthermore, with cortisol decreased to normal levels, continued high ACTH levels did not prevent improvement in depressed mood. The possibility that cortisol may also play a role in the pathogenesis and/or maintenance of the mood disorder in psychiatric patients is discussed.

Adrenocorticotropic Hormone↗
PubMed1985

Anxiety in patients with pheochromocytomas.

Anxiety has been considered an important clinical feature of patients with pheochromocytomas. We studied 17 patients with active pheochromocytoma to determine whether they experienced anxiety that met criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, for either panic disorder or generalized anxiety disorder. Fifty-two patients with primary anxiety disorders were used as a comparison group. Six patients with pheochromocytomas had norepinephrine-secreting tumors and 11 had mixed-secretion tumors, with elevated levels of both epinephrine and norepinephrine. None of the 17 patients described the severe apprehension or fear characteristic of panic attacks and none described agoraphobia. One patient received a diagnosis of possible panic disorder, two met criteria for generalized anxiety disorder, and two met criteria for major depressive episode. Thus, the elevated levels of catecholamines secreted by pheochromocytomas are not sufficient to elicit an anxiety disorder.

Adolescent↗
PubMed1984

Impact of psychodynamic factors on the course and management of patients with pseudocyesis.

Comparing and contrasting two patients with pseudocyesis made it clear that differing psychodynamic factors specific to each patient resulted in divergent ways in which they sought out and used medical care. The propensity of these patients to distort reality was observed to interfere with the usefulness of sonography in convincing them that they were not pregnant. Management recommendations are suggested to aid the obstetrician in designing a treatment approach to assist the patient in accepting the diagnosis, giving up the symptom, and preventing future recurrences.

Adult↗
PubMed1981

Depressed mood and other psychiatric manifestations of Cushing's syndrome: relationship to hormone levels.

Thirty-five consecutive patients with Cushing's syndrome were studied prospectively prior to treatment. A consistent constellation of psychiatric disturbances was found, including impairments in affect (depressed mood and crying), cognitive functions (decreased concentration and memory), and vegetative functions (decreased libido and insomnia). A statistically significant relationship was found between the overall psychiatric disability rating and cortisol and ACTH level. The relationship of depressed mood and hormone levels was examined. Low ACTH levels were significantly associated with milder rather than pronounced depressed mood. The implications of the similarities in psychiatric manifestations between Cushing's syndrome and the primary affective disorders are discussed.

Adrenocorticotropic Hormone↗
PubMed1981

Neuropsychiatric manifestations of patients with Cushing's syndrome. Relationship to cortisol and adrenocorticotropic hormone levels.

Thirty-five consecutive patients with Cushing's syndrome were studied prospectively before treatment. A consistent constellation of neuropsychiatric disturbances was found, including impairments in affect (depressed mood and crying), cognitive functions (decreased libido and insomnia). Thirty-four percent of patients were rated as having a mild, 26% a moderate, 29% a severe, and 11% a very severe psychiatric disability. A statistically significant relationship was found between the overall neuropsychiatric disability rating and cortisol and adrenocorticotropic hormone (ACTH) levels. Patients with adrenal adenomas with high cortisol but low ACTH levels did not have as severe a neuropsychiatric disability.

Adrenocorticotropic Hormone↗
PubMed1980

Psychological problems resulting from parent-to-adolescent renal transplantation.

This paper deals with the ways in which the psychological responses of renal transplant donors and recipients interfere with the developmental tasks of adolescence. The characteristic responses of donors and recipients in general are briefly reviewed. The special problems of the adolescent who has received a transplant from a parent are considered. Interference with the separation-individuation process is discussed. Also considered is the difficulty posed to the development of sexual identity. Excerpts from brief therapy are presented that illustrate the characteristic psychological conflicts described.

Adolescent↗
PubMed1980

Neuropsychological deficits in Cushing's syndrome.

In contrast to well documented reports of medical symptoms in Cushing's syndrome (an endocrine disorder with the hallmark of corticoid overproduction), vague and infrequent references to associated mental changes reflect the subjective nature of previous clinical studies of psychological symptoms. This report presents neuropsychological test findings of 35 Cushing's syndrome patients before initiation of medical therapy, and documents the frequency, nature, and severity of deficits. Performances on the Michigan Neuropsychological Test Battery revealed equivocal or no signs of neuropsychological deficits in 13 patients. Ten other patients had few and mild deficits, eight had moderate and more frequent signs of impairment, and four had frequent and marked deficits in language and nonlanguage tests of higher (cognitive) and/or lower (sensory and/or motor) level cerebral functions. The findings thus indicate varying degrees of diffuse bilateral cerebral dysfunction in two thirds of this population. Impairment was more frequent and severe in nonverbal visual-ideational and visual memory functions. This pattern of deficits is similar to that in patients with other types of diffuse bilateral neuropathological processes such as toxicity, anoxia, and infectious cerebral disorders.

Adult↗
PubMed1979

Incorporation of gerontology into medical education.

Despite the increasing importance of gerontology to medical practice, it has been difficult to incorporate it into the curriculum of most medical schools. The aim of this project was to explore the feasibility of introducing gerontology into medical education by utilizing the framework of an existing clinical program. A gerontologist used the structure and resources of a Psychiatry Consultation-Liaison Program for this purpose. Three groups of target trainees were identified: psychiatry residents on their Liaison rotation; junior medical students on their psychiatry clerkship; and medical-surgical house officers in the general hospital. The objectives were to impart didactic information and to counteract negative attitudes leading to disinterest in evaluating and treating the elderly. The results indicated a positive impact on all three trainee groups, and a diffusion of the gerontologic innovation from the initial locus of a clinical sub-unit into the medical center and the medical school.

Education, Medical↗