Efficacy of histopathology in detecting petrochemical-induced toxicity in wild cotton rats (Sigmodon hispidus).

A variety of chemical mixtures exist in the soil of petrochemical waste sites, and many of these compounds are known immunotoxicants that have been observed to induce immune alterations in wild rodents inhabiting many of these petrochemical waste sites. Conventional histopathological assessments have been widely used with considerable success to investigate immunotoxicity of various agents under laboratory conditions. We hypothesized that histopathologic assessments would be equally sensitive for detecting exposure to complex mixtures of toxicants in cotton rats (Sigmodon hispidus) residing in contaminated habitats. Histopathological parameters were examined from a total of 624 cotton rats that were seasonally collected from 13 petrochemical-contaminated waste sites and 13 ecologically matched reference sites in Oklahoma over a 3-year period. Histopathological examination did not reveal any lesion associated with exposure to petrochemical wastes except renal inclusion bodies. Prevalence and severity of histologic lesions in liver and kidneys of cotton rats were significantly influenced by season, where prevalence and severity were lower in winter than summer on all study sites. These results suggest that the evaluation of toxicity from exposure to contaminants in the soil of industrial waste sites using histopathological assessments is not sensitive enough to detect exposure to the low levels of environmental contaminants present on most waste sites.

Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. I. In vitro bone-marrow progenitor culture.

Bone marrow is extremely sensitive to toxicants, and in vitro culture of bone-marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 microg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU-GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations.

Widespread risks of dental fluorosis in cotton rats (Sigmodon hispidus) residing on petrochemical waste sites.

Fluoride has been identified as a ubiquitous contaminant of soils where petrochemical wastes have been disposed. The purpose of this study was to assess how widespread toxicity risks are to resident vertebrates from chronic exposure to fluoride in the soil of petrochemical-contaminated waste sites. In total, 573 wild cotton rats (Sigmodon hispidus) were examined. The rats that were seasonally collected from 12 contaminated and 12 ecologically matched reference sites across Oklahoma over a 3-yr period. The risks of cotton rats exposed to fluoride were analyzed by means of gross examination, histopathology, and scanning electron microscopy of rat incisors. Cotton rats from reference sites showed no pathologic changes in incisors (98%). In comparison, 46% of cotton rats from contaminated sites had various degrees of dental lesions. The prevalence and severity of dental lesions in cotton rats from contaminated sites were significantly influenced by season. There was a 45% increase in prevalence and a 65% increase in severity of dental lesions from summer to winter. This study demonstrated that cotton rats are very sensitive biomonitors for assessing toxicity risks from soils contaminated with fluoride and that such assessments should consider seasonal influences.

Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. II. Myelotoxicity associated with petroleum industrial wastes.

Various chemical mixtures exist in soil contaminated with petrochemical wastes, yet no comprehensive assessment of their impact on terrestrial ecosystems has been conducted. The purpose of this study was to evaluate hematotoxicity risks to wild populations of cotton rats (Sigmodon hispidus) residing in habitats previously contaminated by petroleum industrial wastes. Resident cotton rats were monitored on nine contaminated sites and nine ecologically matched reference sites in Oklahoma. The possible toxicological interactions of petrochemical wastes on bone marrow was investigated by using the assay of colony formation of granulocyte-macrophage progenitor cells. There was a consistent significant 21 to 39% decrease in the number of colony-forming units of granulocyte-macrophage (CFU-GM) in cotton rats from petrochemical-contaminated sites compared to matched reference sites, with no marked changes in hematological or histopathological parameters. These results suggest that bone-marrow progenitor cell culture is a sensitive indicator for the assessment of ecotoxicity risks associated with petrochemical wastes that are generated by the oil refining industry. Long-term exposure to hazardous wastes associated with the petroleum industry may represent a subtle risk to the hematopoietic system in humans.

Intermittent explosive disorder-revised: development, reliability, and validity of research criteria.

The study of human aggression has been hindered by the lack of reliable and valid diagnostic categories that specifically identify individuals with clinically significant displays of impulsive aggressive behavior. DSM intermittent explosive disorder (IED) ostensibly identifies one such group of individuals. In its current form, IED suffers from significant theoretical and psychometric shortcomings that limit its use in clinical or research settings. This study was designed to develop a revised criteria set for IED and present initial evidence supporting its reliability and validity in a well characterized group of personality disordered subjects. Accordingly, research criteria for IED-Revised (IED-R) were developed. Clinical, phenomenologic, and diagnostic data from 188 personality disordered individuals were reviewed. IED-R diagnoses were assigned using a best-estimate process. The reliability and construct validity of IED-R were examined. IED-R diagnoses had high interrater reliability (kappa = .92). Subjects meeting IED-R criteria had higher scores on dimensional measures of aggression and impulsivity, and had lower global functioning scores than non-IED-R subjects, even when related variables were controlled. IED-R criteria were more sensitive than DSM-IV IED criteria in identifying subjects with significant impulsive-aggressive behavior by a factor of four. We conclude that in personality disordered subjects, IED-R criteria can be reliably applied and appear to have sufficient validity to warrant further evaluation in field trials and in phenomenologic, epidemiologic, biologic, and treatment-outcome research.

Cytochrome P450 induction in feral Cricetid rodents: a review of field and laboratory investigations.

The constitutive and inducible hepatic cytochromes P450 of various feral Cricetid rodents (family Cricetidae, comprising various New World rats and mice, hamsters, gerbils and voles), have been examined in a relatively limited number of field and laboratory investigations. These studies, reviewed herein, have employed substrates and immunochemical reagents that are diagnostic for individual P450 subfamilies of Rattus norvegicus (the common laboratory species derived from the Norway rat, a member of the family Muridae). The results have demonstrated that the feral rodents display hepatic responses to prototypic CYP1A inducers (3-methylcholanthrene, beta-naphthoflavone) similar to those displayed by R. norvegicus and Mus musculus (the common laboratory species derived from the house mouse, another member of the family Muridae). At least one study has demonstrated the induction, by ethanol, of a protein immunochemically similar to CYP2E1 in a Cricetid rodent. In Cricetid rodents, phenobarbital-type inducers cause the induction of a hepatic protein immunologically similar to that primarily induced (CYP2B) in R. norvegicus and M. musculus. The proteins induced in the Cricetid rodents, however, exhibit striking differences in substrate specificity, compared to the proteins induced in R. norvegicus. These results indicate that the previously described differences between the P450 induction responses exhibited by the commonly utilized laboratory species R. norvegicus and M. musculus (family Muridae) and the Syrian hamster and gerbil (family Cricetidae) are observed as a generality for members of the Cricetid family of rodents.

Psychiatric screening in primary care: what do patients really want?

Psychiatric disorders are common in primary care, but underdiagnosed. U.S. physician reluctance to diagnose psychiatric illnesses is partly attributable to the belief that patients do not want their primary care physician to assess mental health. Six hundred one patients in a U.S. general internal medicine practice completed the SCREENER, a self-report questionnaire which screens for 15 psychiatric disorders, and another questionnaire about the SCREENER. Patients were predominantly female, unmarried, black, high school graduates. Only 3% thought that their physician should never evaluate their mental health. More than 60% desired periodic mental health screening, and one third wanted psychiatric assessment only when a problem was suspected. Attitudes toward questionnaire screening were less positive than toward physician interview. Patients were more likely to want screening if they were female, unmarried, young, had a history of mental health treatment, reported psychiatric symptoms, or were in fair-poor subjective physical or mental health.

The influence of ionophores on the duration of xylazine-ketamine anestheisa and the hepatic cytochrome P-450 content of broiler chickens.

This study examined the effects of feeding monensin, lasalocid or salinomycin (at 1x and 2x therapeutic levels for 20 d) on the duration of xylazine+ketamine sleep time and the hepatic cytochrome P-450 content in broiler chickens of different age groups (3- and 6-w-old). The 3-w-old birds fed 120 ppm salinomycin had a reduced xylazine+ketamine sleep time as compared to control (no drug). The 6-w birds had a sleep time similar to the controls. Associated with ionophore feeding was a trend toward P-450 induction when compared to controls. Increased P-450 content was statistically significant in the 3-w birds fed 90 ppm lasalocid and in the 6-w birds fed 200 ppm monensin. Ionophore administration above recommended levels gave conflicting results for duration of xylazine+ketamine sleep time and hepatic cytochrome P-450 levels. The isozymes of cytochrome P-450 responsible for xylazine and ketamine metabolism may be different from those induced by the ionophores. There was no significant age-related difference in ionophore effects on cytochrome P-450 content.

Suicide screening in a primary care setting at a Veterans Affairs Medical Center.

Seven-hundred and three patients from a general medical outpatient clinic at a Veterans Affairs hospital completed the SCREENER, a brief self-report questionnaire that screens for psychiatric disorders. The authors found that 7.3% of the patients had suicidal ideation. The younger and white patients were at increased risk. The risk was increased twelvefold in those patients with subjectively fair or poor mental health, sevenfold in the patients with a history of mental health treatment, and fourfold in the patients with fair or poor perceived physical health. When major depression was controlled for, anxiety and substance abuse disorders continued to show an association with suicidal ideation. The suicidal patients made more visits to their primary care physician. Screening patients for anxiety disorders and drug abuse, as well as depression, is a better approach for identifying suicidal ideation in primary care settings than screening for depression alone and may help prevent suicide and suicide attempts.

Impulsive aggression in personality disorder correlates with tritiated paroxetine binding in the platelet.

BACKGROUND: To examine the relationship between binding parameters of the platelet central serotonergic (5-HT) transporter and measures of aggression and impulsivity in adult human subjects. METHODS: Maximal number of platelet tritiated paroxetine binding sites (Bmax) and dissociation constant (Kd) values were measured in patients with personality disorder (n = 24) and healthy volunteers (n = 12). Measures of aggression and impulsivity included the total score and aggression subscale of the Life History of Aggression, the Motor Aggression factor and the assault subscale of the Buss-Durkee Hostility Inventory, and the total score and motor impulsivity subscale of the Barratt Impulsiveness Scale. RESULTS: The Bmax, but not Kd, values of platelet tritiated paroxetine binding was inversely correlated with the Life History of Aggression total score and aggression score and with the Buss-Durkee Hostility Inventory assault score in patients with personality disorder but not in healthy volunteer subjects. This relationship was independent of influences of factors related to depression, global function, or history of alcoholism or drug abuse. CONCLUSIONS: Reduced numbers of platelet 5-HT transporter sites may covary with life history of aggressive behavior in patients with personality disorder. This may represent another abnormality in 5-HT function in individuals with personality disorder and aggressive behavior.

Effects of feeding Artemisia filifolia and Helenium flexuosum on rabbit cytochrome P450 isozymes.

Six groups of 4 rabbits each were treated as follows: Control; phenobarbital (PB); 3-methylcholanthrene (3MC); proadifen hydrochloride (SKF-525A); Artemisia filifolia and Helenium flexuosum. Prototype P450 inducers (PB and 3MC) increased basal hepatic cytochrome P450 content by 2-3 fold whereas the P450 inhibitor (SKF-525A) had no effect on basal cytochrome P450 content. PB-induction of hepatic microsomes significantly increased the rate of dealkylation of long alkyl chain alkoxyresorufin ethers, benzyloxyresorufin and pentoxyresorufin 47-fold and 17-fold, respectively, but had little or no effect on short alkyl chains. 3MC-induction of microsomes increased dealkylation of all alkoxyresorufin ethers tested, preferentially dealkylating ethers with short alkyl chain in the order: methoxy > ethoxy > propoxy. Artemisia filifolia or Helenium flexuosum had no effect on basal hepatic cytochrome P450 content. However, microsomal dealkylation activity of short alkyl chain alkoxyresorufin ethers (methoxy, ethoxy and propoxy) was inhibited approximately 50%. When these plants are eaten for several days, they may inhibit biotransformation processes in herbivores through the same isoenzymes induced by 3MC.

Primary care patients' reactions to mental health screening.

OBJECTIVE: The authors examined whether there is empirical support for the notion that medical patients are upset by being asked questions about psychiatric disorders. METHOD: Six hundred and one patients attending a primary care clinic completed the SCREENER-a newly developed, brief self-administered questionnaire that surveys a broad range of psychopathology. In addition, they completed a second questionnaire that assessed their attitudes toward the SCREENER. RESULTS: We found a high level of acceptance by patients. The questions were judged easy to answer, and they rarely aroused significant negative affect. Fewer than 2 percent of the patients judged the questions difficult to answer, and fewer than 3 percent were "very much" embarrassed, upset, annoyed, or uncomfortable with the questions. Individuals with a history of psychiatric treatment and poorer current mental health reacted more unfavorably to the questionnaire. CONCLUSIONS: From the patient's perspective, it is feasible and acceptable to use self-administered questionnaires for routine screening of psychiatric problems in primary care settings.

Suicidal ideation among urban medical outpatients.

The prevalence of current suicidal ideation among urban primary care outpatients was assessed, and suicidal and non-suicidal patients were compared with regard to their demographic characteristics and their attitudes toward mental health screening. Twenty (3.3%) patients reported having thoughts of killing themselves. The patients who had suicidal ideation were significantly younger and more frequently divorced. Almost all (97.6%) of the patients indicated that their physicians should inquire about emotional health issues at some time, and the suicidal patients were nonsignificantly more likely to recommend inquiry about psychiatric symptoms at every visit (55.0% vs 37.0%, p < 0.11). Only half of the suicidal patients reported lifetime histories of mental health treatment. The majority (70.2%) of the patients believed that it would be easy to discuss mental health problems with their medical physicians. Among the patients who had previously received psychiatric treatment, the suicidal patients were nearly three times more likely to anticipate that it would be difficult or very difficult to talk to their physicians about psychiatric problems. In contrast, among the patients who had no history of mental health treatment, there was no association between suicidal ideation and anticipated discomfort in talking with their physicians about emotional health.

Is the comorbidity between social phobia and panic disorder due to familial cotransmission or other factors?

BACKGROUND: We previously reported significantly elevated rates of social phobia in relatives of probands with panic disorder compared with relatives of other proband groups. This study further investigates the relationship between social phobia and panic disorder. METHOD: This sample is from a family study that included 193 probands from four mutually exclusive groups (patients with panic disorder, patients with panic disorder and major depression, patients with early-onset major depression, and normal controls) and 1047 of their adult first-degree relatives. Best-estimate diagnoses were completed using DSM-III-R criteria. RESULTS: Social phobia and agoraphobia aggregate in the families of probands with panic disorder without major depression. Social phobia frequently co-occurs with panic disorder in relatives, but the risk for comorbidity does not vary across proband groups. CONCLUSIONS: The familial aggregation of social phobia with panic disorder may be explained by the aggregation of panic disorder in relatives of probands with panic disorder combined with the tendency for panic disorder to occur comorbidly with social phobia in individuals.

Psychiatric screening in geriatric primary care: should it be for depression alone?

Depression in the elderly is highly prevalent, associated with functional disability and increased medical costs, and treatable; however, it is infrequently recognized and treated. The Agency for Health Care Policy and Research has advocated, therefore, increased case-finding efforts for depression in primary geriatric care. Anxiety, substance, and somatoform disorders in the elderly are similarly prevalent, associated with disability and cost, treatable, and also infrequently detected and treated. We believe that psychiatric case-finding in geriatric primary care should attend to these disorders, therefore, as well as to depression. In the present study, we examined whether the association between depressive and nondepressive forms of psychopathology was similar in geriatric and nongeriatric medical patients. We also examined the relationship between each type of pathology and health care utilization and global ratings of physical and mental health. In a VA hospital general medical outpatient clinic, 508 patients completed the SCREENER, which is a brief self-report questionnaire that screens for a range of psychiatric disorders, along with a self-report questionnaire regarding subjective health and medical care utilization. Of these patients, 98% were male, and the median age was 63 years. Patients aged 63 and over were compared to younger patients. In both geriatric and younger adult patients, we found substantial comorbidity between depressive and nondepressive forms of pathology. Moreover, in both age groups, there were significant associations between both depressive and nondepressive symptoms and fair-to-poor self-rated physical and mental health and increased medical care utilization. Approximately half of the cases of nondepressive disorders in the elderly were not comorbid with depression, and thus would not have been detected by screening for depression alone. Therefore, psychiatric case finding in primary care of geriatric males should be directed at anxiety, substance, and somatoform disorders, as well as at depression, for treatment resources to be triaged to maximally decrease morbidity and cost.

Family psychiatric screening instruments for epidemiologic studies: pilot testing and validation.

Family history, a risk factor for psychiatric disorders, is infrequently assessed in epidemiologic studies due to time and cost constraints. We designed a brief computer-scorable instrument, the Family History Screen for Epidemiologic Studies (FHE), which collects a pedigree and screens for 15 DSM-III diagnoses in an informant and in his family members. The FHE was administered to one informant in 77 families in which we had collected pedigrees, interviewed 77 informants and 239 relatives using the Lifetime Anxiety version of the schedule for Affective Disorders and Schizophrenia or the Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, and performed best-estimate diagnoses. We evaluated the accuracy with which the FHE predicted best-estimate diagnoses. For adults reporting on themselves, the FHE demonstrated high levels of sensitivity and specificity for depression (67.4, 75.0) and panic (92.5, 89.2), and low sensitivity and high specificity for substance abuse (33.3, 93.6). For informants reporting on adult relatives, sensitivity was low and specificity was high for depression (35.2, 84.9), panic (20.0, 91.7), and substance abuse (42.1, 93.4). For informants reporting on children, perhaps due to lower prevalence, sensitivity and specificity were poor. The FHE is a good screen for psychiatric disorders in adult informants, but it is not useful for family history. It may be useful in primary care medical settings as a screen for psychiatric history.

Screening for depression in medical patients. Is the focus too narrow?

There is growing consensus that depression is a major public health problem causing significant psychosocial morbidity and mortality which should be addressed by case-finding effects in primary care settings. A large amount of literature has examined the ability of self-report questionnaires to detect depression in medical patients and the results have been encouraging. However, studies of general population and psychiatric patient samples indicate that depression is frequently comorbid with other psychiatric disorders, and that psychiatric disorders other than depression are also associated with significant morbidity and mortality. Consequently, we believe that psychiatric screening in primary care should be broad based. We administered a newly developed, multidimensional questionnaire (the SCREENER), that simultaneously screens for a range of DSM-III-R psychiatric disorders, to 508 medical outpatients attending a VA general medical clinic. Compared with nondepressed cases, the depressed patients significantly more often reported all of the nondepressive symptoms. Nine of the ten nondepressive disorders screened for by the SCREENER were significantly more frequent in the depressed group. Most patients who screened positive for depression also screened positive for at least one nondepressive disorder. Compared with patients who only screened positive for depression, those who screened positive for both depression and a nondepressive disorder rated their physical and emotional health more poorly and made more visits to the doctor. Compared with patients who did not screen positive for any disorder, those who only screened positive for a nondepressive disorder rated their physical and emotional health more poorly, and more frequently had a history of mental health treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members.

Members of the National Depressive and Manic-Depressive Association who have bipolar disorder were surveyed. 59% of respondents had their first symptoms during childhood or adolescence. Long delays between symptom onset, treatment-seeking, and receipt of a bipolar diagnosis were common. 45% of respondents currently experience frequent recurrences. Child/adolescent onset was associated with a positive family history, depressive or mixed initial symptoms, and frequent recurrence, with predominantly depressive symptoms. Frequent recurrences were associated with depressive or mixed initial symptoms and depressive episodes, but not with medication non-compliance. Both child/adolescent onset and frequent recurrence were associated with increased social morbidity, which was diminished by effective treatment. Respondents with frequent recurrences were less likely to be treated with mood-stabilizers, more likely to be treated with anti-depressants, or anxiolytics, and more likely to report past anxiety symptoms and diagnoses. 13% of respondents had no medical insurance, and 15% had failed to take medicine for financial reasons. The treatment of bipolar illness could be enhanced by (a) public health efforts to promote early diagnosis and treatment; (b) ensuring adequate trials of mood-stabilizers for patients with frequent recurrences; (c) further research on bipolar disorder with prominent anxiety symptoms; and (c) improved access to mental health care.