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Biomedical subjects

D D Krahn

Publications and source records attributed to D D Krahn.

At least 19 recordsLinked to original sources

Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings.

The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature. The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness "chronic fatigue syndrome." Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis. In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals. Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity.

Adult

The effects of continuous naltrexone infusions on diet preferences are modulated by adaptation to the diets.

Two groups of male rats were placed on a feeding regimen in which a fat/protein diet and a carbohydrate/protein diet were available ad lib. Naltrexone was infused via osmotic minipumps either at the time the diets were introduced or after one week of adaptation to the diets. In rats adapted to the diets, naltrexone caused a decrease in the intakes of fat/protein and carbohydrate/protein diets. Relative preferences for the two diets were generally unchanged. In contrast, when naltrexone was infused at the time of introduction of the diets, a polarization phenomenon was observed: rats tended to consume nearly all of their daily calories from either one diet or the other. Six rats (out of 10) showed a stronger preference for the carbohydrate/protein diet than did any of the saline-treated rats, while 3 showed a stronger preference for the fat/protein diet than did any of the saline-treated rats. Thus, the effect was not diet- or macronutrient-specific. These preferences became significantly less extreme after termination of naltrexone infusions. Conditioned aversions and naltrexone-induced reductions in exploratory behavior are discussed as potential explanations for this polarization effect. These results indicate that naltrexone has differential effects on the development versus the maintenance of diet preferences. Further, they emphasize the importance of examining individual differences as well as baseline preferences in studies on the control of intake and diet selection.

Adaptation, Psychological

Taste responses and preferences for sweet high-fat foods: evidence for opioid involvement.

Preferences and cravings for sweet high-fat foods observed among obese and bulimic patients may involve the endogenous opioid peptide system. The opioid antagonist naloxone, opioid agonist butorphanol, and saline placebo were administered by intravenous infusion to 14 female binge eaters and 12 normal-weight controls. Eight of the binge eaters were obese. During infusion, the subjects tasted 20 sugar/fat mixtures and were allowed to select and consume snack foods of varying sugar and fat content. Naloxone reduced taste preferences relative to baseline in both binge eaters and controls. Total caloric intake from snacks was significantly reduced by naloxone in binge eaters but not in controls. This reduction was most pronounced for sweet high-fat foods such as cookies or chocolate. No consistent effects on taste preferences or food intakes were observed with butorphanol. Endogenous opioid peptides may be involved in mediating taste responses and preferences for palatable foods, notably those rich in sugar and fat.

Adolescent

The relationship of eating disorders and substance abuse.

Initial interest in the relationship between eating disorders, which occur primarily in women, and substance abuse, which is much more frequent in men than women, stemmed from the observations of Crisp (1968) who noted that chronic anorexics who developed bulimic behavior often abused alcohol. More recently, cross-sectional studies of women with eating disorders have documented prevalences of alcohol and other substance abuse in these women that are much higher than those reported in the general female population. Conversely, women with substance abuse disorders report eating-disordered behavior more often than the general population. This article first presents a definition of eating disorders and then addresses (1) the rate of coprevalence of eating disorders and substance abuse; (2) the mechanism of the coprevalence of these disorders; (3) the clinical similarities of these disorders; and (4) future directions.

Anorexia Nervosa

Stealing in eating disordered patients.

Previous studies have noted high rates of stealing behavior in patients with eating disorders. To assess the significance of stealing in eating disordered patients, the authors compared the eating and purging behavior, levels of psychologic symptomatology, and alcohol use of 181 eating disordered patients with and without a history of stealing. Overall, the patients with a history of stealing had significantly more dysfunctional eating and purging behavior. Those patients with a history of stealing reported significantly more psychological distress including more depression, interpersonal sensitivity, obsessive compulsive behavior, and hostility. The authors conclude that stealing behavior should be assessed in patients with eating disorders as a history of stealing may define a subgroup of more severely impaired patients.

Adolescent

Gender differences in TRH-stimulated TSH and prolactin in primary degenerative dementia and elderly controls.

We performed thyrotropin-releasing hormone (TRH) stimulation testing in 18 nondepressed patients with primary degenerative dementia (10 M, 8F; average age +/- SD = 68 +/- 7) and 12 elderly controls (7M, 5F; average age +/- SD = 61 +/- 6). Six patients were retested approximately 2 years later. Initial Mini-Mental State Examination scores for patients ranged from 2 to 28 (average +/- SD = 18 +/- 6) and the scores for the control subjects were all equal to 30. Protirelin (500 micrograms) was injected iv and blood was sampled at 0, 15, 30, 45, 60, and 90 min for thyrotropin-stimulating hormone (TSH) and prolactin (PRL). There were no significant differences between patients and controls in baseline T4, T3 uptake, TSH, or PRL. No significant differences were found between patients and controls for either TRH-stimulated TSH or PRL at all time points. Duration of illness, severity of dementia, and severity of depressive symptoms did not correlate significantly with stimulation test results. There were, however, significantly greater responses in stimulated TSH and PRL for women compared with men in both patients and controls. Upon repeat testing (n = 6), TRH-stimulated TSH and PRL were not significantly different from the initial results.

Aged

The anorectic effects of CRH and restraint stress decrease with repeated exposures.

Intracerebroventricular (icv) administration of corticotropin-releasing hormone (CRH) or exposure to a restraint stressor causes acute anorexia in rats. However, the effects on food intake of repeated injections of CRH or repeated exposures to restraint stress have not been previously reported. As the effects of these more chronic CRH and stress treatments may be of greater relevance to emerging hypotheses of the pathogenesis of human eating and affective disorders, we measured the changes in food intake and body weight of rats after repeated central injections of CRH. In two experiments using two different daily dosages of CRH and two different schedules of administration, we found that the anorectic effect of CRH decreased over repeated injections. Weight gain was slowed significantly only in the high-dose experiment. Rats may become tolerant to the anorectic effects of CRH delivered by repeated icv injections. These findings have important implications for hypothesized mechanisms of anorexia nervosa and/or depression.

Animals

Effects of preferential delta and kappa opioid receptor agonists on the intake of hypotonic saline.

A previous study has implicated central mu opioid receptors in the preference for salt solutions. Because mu, kappa and delta receptors are all thought to play a role in food intake and/or the mediation of palatability, we performed a series of experiments to determine whether preferential agonists at kappa and delta receptors might also stimulate the intake of salt solutions. When injected centrally into nondeprived rats, two selective agonists at delta receptors caused increases in the intake of 0.6% saline; the intake of concurrently available water was either unchanged or slightly increased. The selective kappa agonist U-50,488H had no effect on water or saline intake, whereas the preferential kappa agonist DAFPHEDYN caused a delayed increase in saline intake. These results indicate a role for central delta receptors in the preference for salt solutions, and are consistent with the suggestion that opioids play a role in the mediation of palatability.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

The effects of morphine on diet selection are dependent upon baseline diet preferences.

It has been reported that morphine causes a selective increase in the intake of dietary fat. Because we have noted considerable variability among rats in their preferences for carbohydrate and fat, we reasoned that the effect of morphine on diet selection may differ in fat-preferring vs. carbohydrate-preferring rats. Male Sprague-Dawley rats were given ad lib access to separate sources of carbohydrate, fat and protein (Experiment 1), or to a carbohydrate/protein and a fat/protein diet (Experiment 2). After daily baseline intakes of the diets were determined, all rats were tested for feeding responses to subcutaneous injections of morphine (0, 2 and 10 mg/kg). Significant positive correlations were found between baseline daily intake of a given diet and the effect of morphine on the intake of that diet. Generally, morphine increased carbohydrate intake in carbohydrate-preferring rats, and increased fat intake in fat-preferring rats. These results suggest that the effect of morphine is to increase intake of a preferred diet rather than to increase intake of a specific macronutrient.

Analysis of Variance

The adenosine agonist N6-R-phenylisopropyladenosine (R-PIA) stimulates feeding in rats.

Administration of adenosine and agonists of the adenosine receptors to rats results in hypoactivity, hypothermia, muscle relaxation and antinociception. In the present study, we found that the adenosine ligand, N6-R-phenylisopropyladenosine (R-PIA), increased food intake in rats at a time in the day when rats normally eat very little food or none at all. Feeding was not reliably stimulated upon the first exposure to R-PIA, but was clearly increased following repeated administration of this agonist. Other adenosine agonists, namely 2-chloradenosine and 5'N-ethylcarboxamide adenosine, failed to alter feeding after a single injection or after repeated exposure. The adenosine antagonist, caffeine, did not block R-PIA's effect on food intake, whereas the opioid antagonist, naloxone, blocked R-PIA-induced eating. These data suggest that R-PIA stimulates feeding independent of the A1 or A2 adenosine receptors.

2-Chloroadenosine

Psychoneuroendocrine effects of methadone maintenance.

A variety of neuroendocrine and psychiatric dysfunctions have been demonstrated in humans maintained on opiates, but both have not previously been examined in the same population. We performed a series of neuroendocrine challenge tests in men participating in a methadone maintenance clinic and in normal controls. Psychiatric diagnoses were made with DSM-III Criteria, using the Diagnostic Interview Schedule, and subjects also completed the Symptom Checklist. Our results in the methadone group suggest (a) near-maximal stimulation of prolactin secretion, with a blunted prolactin response to insulin hypoglycemia, (b) mild suppression of cortisol levels, but an exaggerated cortisol response to stimulation, (c) a delayed and inhibited insulin response to food ingestion with resulting mild hyperglycemia, (d) low body weight, but elevated calorie ingestion, and (e) inability to concentrate urine when dehydrated, which was partially corrected by administration of arginine vasopressin. Phobic disorder was associated with a lower prolactin response to both inhibitory and stimulatory challenges. Depression did not appear to be related to the increased cortisol response to stimulation. These results suggest several potentially fruitful areas for future investigation, including the prolactin system and anxiety disorders, nutrient ingestion and metabolism, and posterior pituitary function.

Adrenocorticotropic Hormone

Salivary levels of putative cariogenic organisms in patients with eating disorders.

The present study examined the hypothesis that women with eating disorders associated with a history of chronic vomiting can be characterized by a salivary flora with high levels of aciduric organisms, such as, mutans streptococci, lactobacilli and yeast. Three groups of female subjects were studied: vomiting bulimics (G1; n = 14), and comparison groups selected for high Streptococcus mutans (G2; n = 13), and low S. mutans levels (G3; n = 12). The prevalence and levels of mutans streptococci, lactobacilli and yeast tended to be higher in bulimics than in non-bulimics. The bulimics had significantly higher levels and higher prevalence of Streptococcus sobrinus than the non-bulimics. A high S. sobrinus colonization may be a marker for a history of vomiting in bulimia.

Bulimia

Corticotropin-releasing hormone: possible role in eating disorders.

It has been hypothesized that corticotropin-releasing hormone (CRH) is an integral mediator in the pathophysiology of anorexia nervosa. This hypothesis is based on a) studies on patients with eating disorders which found elevated CRH levels in the cerebrospinal fluid and an abnormal response of the hypothalamopituitary (HYPAC) axis to intravenous CRH, and b) the discovery that the central administration of CRH to rats causes an acute anorectic state. Human and animal data supporting this hypothesis are reviewed, and important problems with the data base and the interpretation of these data are discussed. Appropriate directions for future research are highlighted.

Animals

Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects.

Corticotropin-releasing factor (CRF) has potent behavioral effects when administered intracerebroventricularly to rats. CRF and its receptors are found in an uneven distribution in the brain. In an effort to localize the site of the anorectic effect of CRF, exogenous CRF or saline was injected into cannulas directed toward the paraventricular hypothalamic nucleus (PVN), lateral hypothalamus, ventromedial hypothalamus, globus pallidus, or striatum of rats. CRF decreased food intake only when injected into the PVN. In subsequent experiments PVN injections of CRF were shown to (1) increase grooming and movement; (2) not induce a conditioned taste aversion to saccharin in a single bottle test; and (3) inhibit the increase in feeding induced by injections of norepinephrine into the PVN. These results suggest that CRF induces not only anorexia, but also increased movement and grooming by action in the PVN.

Animals

Effect of morphine and nalmefene on energy balance in diabetic and non-diabetic rats.

Male rats made diabetic by intravenous injection of streptozotocin were used to evaluate the effect of the diabetic state on morphine- and nalmefene-induced changes in food intake and body weight. Morphine increased 4 hour food intake in non-diabetic rats after an initial injection, but increased intake in diabetic rats only after repeated injections. Unlike short term measurements, morphine decreased food intake when measured over 24 or more hours in both groups. Chronic injection of morphine decreased body weight only in non-diabetic rats. Feed efficiency data suggest that morphine had a more potent effect on energy balance in the non-diabetic rats. The opioid antagonist, nalmefene, did not alter body weight in either group and only altered food intake in the diabetic animals. These data are in concert with other reports indicating that the diabetic state renders animals less responsive to the effects of morphine on nociception and smooth muscle contraction.

Animals

Bulimia in college women: incidence and recovery rates.

In a longitudinal survey of college freshmen, the incidence of bulimia nervosa was 4.2 cases per 100 women per year. Prevalence remained stable (2.9%-3.3%) as new cases were offset by partial remissions. Some women continued bulimic behaviors without meeting the DSM-III-R criteria.

Bulimia