Suicidal behaviour, social networks and psychiatric diagnosis.
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Biomedical subjects
Publications and source records attributed to C L Williams.
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Stress in humans commonly results in gastrointestinal dysfunction, which is characterized by its symptomatology because the etiology is completely unknown. We developed an animal model in which to study the effects of stress on the gastrointestinal tract, and characterized the model as a stressor by evaluating endocrine and analgesic responses to mild restraint. Mild restraint (wrap restraint) elevated plasma levels of adrenocorticotropic hormone and beta-endorphin, and caused analgesia. The different regions of the gastrointestinal tract responded differently to the stress stimulus. Gastric emptying was not affected, small intestinal transit was inhibited, and large intestinal transit was stimulated by stress, and there was an associated increase in fecal excretion. Wrap-restraint stress did not result in the formation of ulcers. There was a strong correlation between stress-induced adrenocorticotropic hormone release and stress-induced intestinal dysfunction over a 24-h period that suggested a circadian influence. However, neither exogenous adrenocorticotropic hormone nor beta-endorphin had any effect on intestinal transit. Furthermore, neither adrenalectomy nor hypophysectomy prevented the response of the intestine to stress, suggesting that neither adrenal nor pituitary-derived factors are responsible for mediating the effects of stress on the gut. We conclude that wrap-restraint stress produces different effects on different regions of the intestine, suggesting that the small and large intestines are independently regulated and can respond differently to different stimuli. There were similarities between the intestinal effects of wrap-restraint stress in rats and intestinal symptoms associated with stress and irritable bowel syndrome in humans. Therefore, wrap restraint may be an appropriate animal model in which to study stress-related intestinal dysfunction. The mechanisms by which stress affects intestinal transit are still unresolved; however, the intestinal effects of stress are not mediated by either pituitary or adrenally derived factors.
An analytical framework is suggested for the economic evaluation of policies to improve the management of hospital infection. Consideration of the costs and benefits to be expected from improved policies implies the existence of an optimal infection rate which is higher than the minimum attainable. It follows that hospitals can and probably do spend too much on infection control in, at least, some areas. This optimal approach is not operational at present but its data requirements might be thought of as an agenda for future research. In the meantime, progress in infection control economics depends on a piecemeal approach. An example is given in the estimation of the cost savings attributable to an improved antibiotic prescribing policy at the Royal Liverpool Hospital.
Striational autoantibodies (StrAb) are a useful serologic marker of thymoma in patients with myasthenia gravis (MG). We compared a standard immunofluorescence method with a new enzyme immunoassay (EIA) for detection of StrAb. Retrospective testing of 264 stored sera by the two methods yielded well-correlated results (58 sera were positive by both assays; r = 0.8). For 104 patients with spontaneously acquired MG or thymoma, results were 100% concordant, of which 53% were positive. For 34 recipients of D-penicillamine, StrAb were found in 15% by EIA and in 6% by immunofluorescence. StrAb were detected in two of four bone marrow recipients by EIA and in one by immunofluorescence. Prospective testing of 434 fresh sera (of which 49 were positive by the two methods) yielded discordant results in only 4. Serial EIA quantitation of StrAb in two patients with MG and thymoma proved useful in monitoring immunosuppressant therapy and in a third patient predicted recurrence of the tumor. A high prevalence of StrAb was detected by both assays in elderly patients with spontaneous MG, but StrAb were more readily quantifiable by EIA. The EIA method proved to be highly sensitive and specific for detecting StrAb in patients with thymoma with and without MG, in patients treated with D-penicillamine, and in those with graft-versus-host disease after bone marrow transplantation.
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A total of 1,677 members of GROW, a mutual-help organization, were surveyed about the reasons they joined GROW and their perceptions of its effectiveness in meeting their needs. The organization was founded 30 years ago to enhance the rehabilitation of former mental patients, but it now includes members who have never been treated for mental illness. Cluster analysis of the survey data revealed five distinct groups of members. One group sought relief of symptoms, while others sought a supportive community, help in recovering from trauma, help in coping with bereavement, or the opportunity to help others. The interests of the different types of members in GROW, and in other mutual-help organizations, may be at odds because some members may need social support that encourages change (facilitative support), while others may need social support that provides stable relationships (palliative support).
Several phenylhydrazone derivatives of oxymorphone [phenylhydrazone and p-nitrophenylhydrazone (OxyPNPH)] as well as oxymorphonazine produce a wash-resistant inhibition of radiolabeled opioid binding, suggesting nonequilibrium binding to opiate receptors. All are agonists and, in an effort to correlate their prolonged inhibition of binding with their pharmacology, we examined their analgesic actions in vivo. Dose-response curves at 1 hr revealed similar potencies of oxymorphone and the derivatives, with the exception of OxyPNPH which was significantly less potent. After 10 hr, oxymorphone at doses up to 50 mg/kg did not demonstrate any effect. In contrast, OxyPNPH at 25 mg/kg elevated tail-flick latencies from 2 to over 8 sec after 10 hr. The 50-mg/kg dose elevated latencies to approximately 5 sec after 24 hr. Oxymorphonazine and oxymorphone phenylhydrazone also produced a prolonged analgesia, although not as effectively as OxyPNPH. The prolonged analgesic actions of OxyPNPH were highly dependent upon a critical period of 2 to 3 h immediately after injection. Blockade of receptors during this period with naloxone prevented analgesia at all time points examined. If the long duration of action of OxyPNPH resulted simply from a long half-life and persistent-free compound within the brain, analgesia should have returned by 8 hr, at which time naloxone has been eliminated. The absence of analgesia 8 hr after both OxyPNPH and naloxone argues against simple pharmacokinetic mechanisms for the prolonged analgesia and is consistent with persistent receptor occupation. OxyPNPH (25 mg/kg) administered in vivo lowered radiolabeled opioid binding effectively in brain membranes despite extensive washing. OxyPNPH lowered mu1 binding by approximately 60% and mu2 binding by 35% whereas delta binding was not lowered significantly.
The effect of pretreatment with naloxonazine on opioid-mediated antinociception against a thermal stimulus (55 degrees C warm-water tail-flick test) and inhibition of gastrointestinal transit at supraspinal and spinal levels was studied in unanesthetized mice. The mu-selective agonist [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAGO), the delta-selective agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) and the reference mu-acting agonist morphine, all produced antinociception after either i.c.v. or intrathecal(ly) (i.t.) administration. Morphine and DAGO, but not DPDPE, inhibited gastrointestinal transit after i.c.v. administration, whereas all three agonists slowed gut propulsion when given i.t. A single s.c. naloxonazine pretreatment, 35 mg/kg given 24 hr earlier, failed to displace the dose-response line for i.c.v. DPDPE antinociception but produced a marked rightward displacement of the i.c.v. morphine and DAGO dose-response lines for antinociception. In contrast, naloxonazine (35 mg/kg) pretreatment did not alter the antinociceptive effects of i.t. morphine, DAGO or DPDPE. The effects of naloxonazine pretreatment on inhibition of gut propulsion were the converse of those observed for antinociception at supraspinal and spinal sites; naloxonazine had no effect on the antitransit properties of i.c.v. morphine and DAGO but inhibited the antitransit properties of all three agonists when they were given i.t. These results support the view that opioids may produce their supraspinal antitransit effects at a receptor different from that mediating antinociception; morphine and DAGO mediate their antitransit effects at a naloxonazine-insensitive site, whereas their antinociceptive effects are produced at the naloxonazine-sensitive receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Uteroglobin, a secretory protein of rabbit uterine epithelium, was localized by the direct immunoperoxidase method in control and hCG-induced pseudopregnant rabbits. In control rabbits, uteroglobin was confined to the apical cytoplasm of nearly all cells of the endometrial epithelium. The induction of pseudopregnancy resulted in a pronounced continuing increase, through 4 days post-hCG administration, in the absolute number of epithelial cells engaged in uteroglobin synthesis. Furthermore, the endoplasmic reticulum was more intensely stained for uteroglobin than in the epithelial cells of control rabbit endometrium. Thus, the increased production of uteroglobin, in response to hormonal stimulation, appears to be achieved both through an increase in the amount of uteroglobin synthesized by a given cell as well as by an increase in the number of cells involved in uteroglobin synthesis. Concurrent with the increase in the number of cells synthesizing uteroglobin, an increase in the number of unstained cells first appeared at the second day of pseudopregnancy, during the period of maximal epithelial proliferation. However, within those cells containing uteroglobin on the second day following injection with hCG, most staining was limited to the perinuclear membrane. At various times following hCG administration, a number of scattered cells, intensely stained for uteroglobin, were observed in the uterine epithelium. Based upon ultrastructural studies, failure to exclude trypan blue, and the presence of intra-mitochondrial uteroglobin, they were identified as either dead or dying cells.
The care of infants and toddlers in nursery school and day-care centers in increasingly large numbers over the past decade poses special problems with respect to communicable disease control. This age group is particularly susceptible to those infectious agents (bacterial, viral, and parasitic) spread by close personal contact. This study describes an outbreak of Haemophilus influenzae type b meningitis in a large nursery school in Westchester County, New York. Organized efforts to control the outbreak through recommendation of rifampin prophylaxis were undertaken and evaluated. Compliance following the first case of meningitis was unacceptably low (45% of children and 33% of staff). Following the second case, however, compliance rose to 90% among child attendees and 79% among staff. Recommended procedures for implementation of control measures are described.
The effects of exogenous and endogenous steroids on components of female sexual behavior of neonatal male and female rats were investigated. In Experiment 1, 4-day-old rats were treated with 0, 0.1, 1.0, 10, or 100 micrograms/10 g body weight estradiol benzoate (EB) and were tested 44 hr later. In Experiment 2, male rats castrated within 24 to 48 hr of birth were compared with sham operated controls and castrates given steroid replacement. The results indicated that most 6-day-old pups will display lordosis and ear wiggling; therefore, the display of these responses is not dependent upon exogenous steroids. However, a fine-grained behavioral analysis revealed that EB treatment increased the frequency, duration, and intensity of lordosis and the frequency of ear wiggling in infant females, and it increased lordosis duration in males. Castration of infant males decreased the likelihood that male infants would display lordosis, whereas testosterone replacement restored behavior to control levels. These data question the concept that organizational and activational actions of estrogens occur during completely separable times in development and should provide new insights into the development of estrogen receptor function and the process of sexual differentiation of brain and behavior.
Six-day-old male and female rats display lordosis and ear wiggling in response to tactile stimulation of the flanks and rump, without priming by exogenous estrogen. The involvement of various brain regions in these behaviors, which resemble components of adult female sexual behavior, was examined by making acute transections along the neuraxis from the olfactory tract to the medulla in 6-day-old rats. Four to 5 hr after the transection procedure, pups were tested for lordosis and ear wiggling. Lordosis was severely reduced or eliminated in pups with cuts through the hindbrain or diencephalon (above the level of the mammillary bodies) but was relatively unaffected by cuts through the posterior hypothalamus and rostral tegmentum and by cuts rostral to the anterior hypothalamus. Ear wiggling was disrupted by transections throughout the hindbrain and was facilitated only in females by transections throughout the forebrain (anterior to the mammillary bodies). These data suggest that facilitation from the hypothalamus is required for lordosis in the infant rat and the forebrain inhibitory systems for ear wiggling are functional in female infants by 6 days of age. Similarities and differences between the neural control of lordosis and ear wiggling in infant and adult rats suggest that the infant sex-like behaviors may be precursors of adult female sexual behavior.
The biochemical identities of several antigens to which striational antibodies bind were determined by using serum antibodies and monoclonal antibodies from two patients with myasthenia gravis. The monoclonal antibodies were secreted by EBV-transformed B-lymphocyte clones obtained from thymus and thymoma. Serum and monoclonal antibodies reacted with discrete components of the skeletal muscle sarcomere, giving rise to several different patterns of immunofluorescence staining. Immunoblot analyses and enzyme-linked immunosorbent assays revealed three different antibody specificities: myosin, alpha-actinin, and/or actin. Individual monoclonal StrAb reacted with both muscle and nonmuscle isotypes of actin or myosin. It is noteworthy that contractile proteins (1) are associated with acetylcholine receptors (AChR) in plasma membranes, and (2) are biochemically altered in transformed cells. It is therefore conceivable that the release of neoantigenic AChR-associated contractile proteins from thymic epithelial cells undergoing neoplastic transformation may provide the immunogenic stimulus for production of StrAb. More precise definition of StrAb specificities in individual patients with MG and/or thymoma might provide a basis for diagnostic and/or prognostic classification of these diseases. Furthermore, the monoclonal antibodies will be useful in experimentally testing the potential pathogenicity of StrAb.
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A new stress model in rats produced changes in intestinal function that resemble patterns of intestinal dysfunction associated with stress in humans: small intestinal transit was inhibited, large intestinal transit was stimulated, and fecal excretion was stimulated. To evaluate the role of corticotropin-releasing factor (CRF) in mediating the effects of stress on the intestine, we studied the actions of exogenous CRF on small and large intestinal transit in the rat and characterized the effects of pharmacological blockade of CRF receptors on stress-induced intestinal dysfunction. Administration of exogenous CRF (0.3-10.0 micrograms iv or icv) resulted in dose-related inhibition of gastric emptying, inhibition of small intestinal transit, stimulation of colonic transit, and stimulation of fecal excretion. The actions of exogenous CRF mimicked the effects of stress on the motor activity of the gastrointestinal tract. Administration of alpha-helical CRF-(9-41) (50 micrograms iv or icv), an antagonist of CRF, prevented the stress-induced increase in large intestinal transit and the associated increase in fecal excretion. These data suggest that endogenous CRF may mediate stress-induced changes in colonic function.
Increased food or milk intake in response to insulin-induced hypoglycemia cannot be demonstrated in the rat until pups reach weaning age. However, when food and suckling are withheld from insulin-treated 5- to 25-day-old rats until their altered blood glucose levels return to normal, their rate of milk intake via suckling from their anesthetized dam is increased over saline-treated control pups. This postglucoprivic action of insulin could not be demonstrated in rats consuming wet mash until pups reached 25-30 days of age. Nonnutritive oral stimulation from dry suckling during the glucoprivic episode is sufficient to disrupt postglucoprivic suckling in 20-day-old rats. In contrast consuming a small quantity of wet mash became an effective inhibitor of postglucoprivic suckling only when pups reached 25 days of age. These data demonstrate the existence of an insulin-sensitive neural system for suckling and feeding in infant rats and point to the involvement of multiple and changing oral factors during development in insulin-induced postglucoprivic feeding.
Psychological testing of minority patients is a frequently debated issue, not only in the scientific literature, but in the mass media, the courts, and legislative bodies. A historical overview of the controversy illustrates past abuses in such testing, but a closer look at methodological issues concerning cognitive-intellectual tests and objective personality assessment illustrates that the tests can be appropriately used with minority patients. Suggestions for appropriate use, backed by case illustrations, include gaining an understanding of a patient's cultural background; using interpreters and culture-appropriate reinforcers; supplementing formal testing with informal procedures; making sure patients understand required tasks; and taking into account ethnicity and social class during interpretation of results.
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