Use of psychoactive drugs in nursing homes.
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Biomedical subjects
Publications and source records attributed to J M Gorman.
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Immune mechanisms are thought to be important in a subpopulation of patients with schizophrenia. We examined the specificity of neural antibodies in patients with schizophrenia to identify a possible antigen. Serum antibodies from patients with schizophrenia and control subjects were tested for binding to protein extracts of human neuroblastoma cells by western blot. Protein antigens were characterised by aminoterminal and internal aminoacid sequence analysis. 14 of 32 (44%) otherwise healthy patients with schizophrenia had antibodies to a neuroblastoma protein of molecular weight 60 kDa. By partial sequence analysis, this protein was identified as the 60 kDa human heat-shock protein (hsp) that is the P1 mitochondrial protein, and which is 50% homologous to the mycobacterial 65 kDa hsp. Antigens that crossreact with hsp65 have been implicated in the pathogenesis of adjuvant-induced arthritis in rats and autoimmune diabetes in mice. Of 100 normal subjects or disease controls, antibodies to hsp60 were found in only 8 patients, all of whom had active infectious or inflammatory disease. Our results support the presence of abnormal immune reactivity involving hsp60 in a subset of patients with schizophrenia. The immune response may be related to the pathogenesis of the disease.
Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks.
To assess the role of noradrenergic stimulation during lactate-induced panic, ten patients with panic disorder who panicked during a standard sodium-lactate infusion underwent a repeat infusion following intravenous clonidine pretreatment. Although clonidine significantly lowered prelactate systolic blood pressure, the drug did not significantly lower prelactate anxiety levels, as reflected by the Acute Panic Inventory (API). Clonidine blocked lactate-induced panic in four of ten subjects, a significant effect. Clonidine treatment also significantly attenuated lactate-panic symptoms, as reflected by time to panic and API comparison between trials. Nevertheless, over half the subjects still panicked in response to lactate despite clonidine. This preliminary study suggests that reduction of central noradrenergic activity by clonidine, at least at the dosage levels employed in the current study, only partially attenuates panic response to lactate. Noradrenergic theories of panic may not therefore fully account for lactate panicogenesis.
To evaluate serotonergic (5-hydroxytryptamine) function in obsessive-compulsive disorder, behavioral and neuroendocrine responses to m-chlorophenylpiperazine (m-CPP; 0.5 mg/kg orally) and fenfluramine hydrochloride (60 mg orally) were examined in 20 patients and 10 healthy controls under double-blind, placebo-controlled conditions. Following m-CPP, but not fenfluramine or placebo, 55% (11/20) of the patients with obsessive-compulsive disorder experienced a transient exacerbation of obsessive-compulsive disorder. Prolactin response was blunted in patients following m-CPP but not following fenfluramine. Patients with greater behavioral response to m-CPP had smaller prolactin responses. Cortisol response to m-CPP and fenfluramine did not significantly differ between the groups. Behavioral and neuroendocrine responses appeared divergent. This does not suggest simply upregulation or downregulation of 5-hydroxytryptamine receptors, but rather complex mechanisms involving multiple neurotransmitter and neuromodulator systems.
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OBJECTIVE: To further the understanding of lactate-induced panic in patients with panic disorder, the authors examined cisternal lactate and carbon dioxide levels in nonhuman primates after infusions of sodium lactate comparable to those used in studies of human beings. METHOD: CSF and venous blood lactate, pH, PCO2, PO2, and bicarbonate were measured in five ketamine-anesthetized nonhuman primates, without mechanical ventilation, before and after they underwent infusions of sodium lactate. In addition, the same measurements were made for three of the five subjects who were given saline infusions. RESULTS: Despite the development of the characteristic peripheral biochemical effects of infused sodium lactate--increased lactate and bicarbonate levels and metabolic alkalosis--no increases in central lactate or carbon dioxide levels were observed. Saline infusions produced no biochemical effects on venous and cisternal measures. CONCLUSIONS: The results of this study are in keeping with previous findings of nonpermeability of the blood-brain barrier to anionic compounds such as lactate. They therefore support theories of lactate panic based on cognitive and/or brainstem misevaluation of peripheral somatic sensations.
OBJECTIVE: The authors examined whether deaths of lovers and close friends from AIDS increased the frequency of depressive symptoms and depressive disorder in a group of homosexual men. METHOD: Two hundred seven volunteer male homosexual subjects were interviewed in New York City in 1988 and 1989. Depressive symptoms were measured with the Hamilton Rating Scale for Depression, administered by a clinician, and two self-report symptom checklists. Subjects were evaluated for major depression with the Structured Clinical Interview for DSM-III-R. Each subject also reported the number of lovers and close friends who had died of AIDS 1) since the beginning of the epidemic in 1981 and 2) in the 6 months preceding the interview. RESULTS: Neither the overall level of depressive symptoms, the presence of specific symptom clusters, nor the presence of a diagnosed depressive disorder was related to the number of AIDS deaths a subject reported in either time frame. In contrast, bereavement reactions specific to loss, namely, preoccupation with and searching for the deceased, were more common in subjects with greater numbers of losses. The findings for depressive symptoms and major depression are not readily explained by measurement artifact, overrepresentation of asymptomatic subjects among study volunteers, habituation effects, numbness, or shallowness of attachments in the subjects. CONCLUSIONS: Changes in normative expectations regarding AIDS deaths and mobilization against AIDS within the gay community may account for the lack of association between the number of losses resulting from AIDS and the presence of depressive symptoms and depressive disorder.
Twenty panic disorder patients with mitral valve prolapse showed amelioration of prolapse on repeat echocardiogram after treatment for panic disorder. This effect was significant when compared to repeat echocardiograms in eight psychiatrically normal control subjects with mitral valve prolapse.
OBJECTIVE: Prolactin is a neurohormone that may be secreted in response to stress and also has regulatory effects on the immune system. Some, but not all, studies suggest that prolactin levels are higher than normal in persons with HIV infection. The authors measured prolactin levels in HIV-positive and HIV-negative homosexual and bisexual men to assess possible differences in levels and then examined relationships between prolactin level and measures of medical status, anxiety, depression, stress, and neuropsychological test performance. METHOD: Blood for prolactin level determination was obtained from 121 HIV-seropositive and 79 HIV-seronegative homosexual and bisexual men enrolled in a longitudinal study. The men also underwent a daylong assessment that included medical, immunological, psychiatric, psychosocial, psychosexual, and neuropsychological evaluations. RESULTS: There was no statistically significant difference in serum prolactin level among the seronegative men, the seropositive men with no or minimal physical symptoms, and the seropositive men with significant physical symptoms of HIV infection. Furthermore, within the HIV-seropositive group, the correlations between serum prolactin level and measures of depression, anxiety, stress, and neuropsychological test performance were all nonsignificant. CONCLUSIONS: Serum prolactin level does not seem to respond to HIV infection or to be related to stress or psychiatric symptoms in HIV-infected men. As none of the subjects had AIDS, the possibility cannot be ruled out that prolactin level increases in very late stages of HIV infection.
BACKGROUND: The human immunodeficiency virus (HIV) epidemic has increasingly involved intravenous drug users. Few studies have attempted to define its clinical and laboratory characteristics in this population. METHODS: We recruited 223 intravenous drug users from New York, NY, for a prospective study of the natural course of HIV infection. Medical history, physical examination, medical staging, and immunologic assessments were performed at 6-month intervals. We examined the baseline findings among this cohort. RESULTS: Of the total cohort, 65.9% were men and 34.1% were women, with 70.9% African American, 12.6% white, 11.7% white Latino, and 4.9% black Latino. At baseline, 44.4% were HIV negative and 55.6% were HIV positive. No significant association was noted between ethnicity, gender, and serologic status. Also no significant difference was noted for homelessness either across serologic status or gender. There was a trend toward an association between gender and use of drugs during the week before interview; the women showed higher drug use. A significant association was noted between HIV serologic status and reported history of pneumonia, oral candidiasis, cough, night sweats, fever, and lymphadenopathy on physical examination. In a regression model, white blood cell count, hematocrit, symptom/sign complex score, and CD4 cell number were significantly associated with HIV status. CONCLUSION: This study provided important historical, clinical, and immunologic characteristics that are useful in the identification and evaluation of the HIV-infected intravenous drug user.
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The antipanic utility of imipramine and monoamine oxidase inhibitors has led to hypotheses of noradrenergic and/or serotonin (5-HT)-related abnormalities underlying panic disorder (PD) and its agoraphobic complications. Further data support significant antipanic effects for agents with acute 5-HT reuptake blockade effects. It is unlikely that ameliorative effects observed following chronic administration of 5-HT drugs remain 5-HT specific. Despite a range of recently discovered 5-HT receptor subtypes, evidence for a specific receptor abnormality in PD is lacking. Preclinical studies suggest an important role for 5-HT effects in several animal models of anxiety, including separation-induced infant protest responses and respiratory modulation. Induction of anxiety with putative 5-HT agents such as meth-chloro-phenylpiperazine and fenfluramine lend further support to 5-HT involvement in anxiety states. Critical behavioral, physiologic, and neuroendocrine differences between putative 5-HT anxiogens and "classic" panicogens, such as lactate and carbon dioxide are discussed. We propose that 5-HT agents mediate antipanic effects through amelioration of a deranged internal evaluative mechanism along cybernetic lines, rather than simple augmentation or reduction of 5-HT function.
Eight unrestrained macaques were observed for 2 hours following either two oral doses of yohimbine (0.2 mg/kg and 2.0 mg/kg) or placebo administration. Four of the subjects were normally reared and four subjects had early maternal and social deprivation. In the normal subjects, yohimbine, at both doses, produced increased tension and enervation and decreased species-typical "normal" behaviors. In deprivation-reared subjects, low-dose yohimbine produced reductions in tension and enervation, and increases in "normal" behaviors. High doses of yohimbine diminished behavioral score differences between groups. The prominent increases in enervation observed in normally reared subjects suggests that yohimbine is not unequivocally anxiogenic. Moreover, early social deprivation may alter the pattern of response to yohimbine, perhaps as a result of aberrant neurodevelopment. This study reflects the role of experiential factors in determining patterns of affective response to putative anxiogenic agents.
We evaluated the extent to which depressive disorders, psychiatric distress, and psychosocial stressors are related to three measures of human immunodeficiency virus (HIV) illness, both cross-sectionally and during a 6-month period, in a community sample of 124 HIV-positive homosexual men. The dependent variables are immune status measured by CD4 and CD8 cell subsets, number of signs and symptoms commonly associated with HIV infection, and a cumulative index of HIV illness stage. We chose to focus on CD4 cell count because it is the immune marker most closely linked to the clinical consequences of HIV infection. We found no relationships between the independent variables and immune status or illness stage. The HIV-positive men who were depressed or distressed or who reported more life stressors had no greater immunosuppression or more advanced illness stage than did the others, either concurrently or across occasions. We did find a suggestive pattern of association between depressive disorders, distress, and stressors and the number of HIV-related symptoms, which warrants further study.
Although much is known about the virus believed by most experts to be the cause of the acquired immunodeficiency syndrome and about its pathogenic actions, major areas of ignorance remain. Among these are the reasons for the varying time between infection with human immunodeficiency virus and development of acquired immunodeficiency syndrome, the relationship between neurologic and medical aspects of the disease, the time course of neuropsychological findings, and the prevalence of psychiatric morbidity. We assessed 124 homosexual men who were positive for human immunodeficiency virus and 84 who were negative for the virus. In this article we describe the study design, method of recruitment, and medical and demographic characteristics of the cohort, which will be followed up for 5 years.
Despite numerous reports of the psychiatric consequences of human immunodeficiency virus infection, few reports describe systematic diagnostic assessments of people with human immunodeficiency virus infection. We studied the results of standardized clinical assessments of current and lifetime psychopathology in a large group of homosexual men whose serologic status was known. Results indicated low rates of current mental disorders but very high rates of lifetime major depression and alcohol and other psychoactive substance abuse and dependence disorders. Measures of severity of psychopathology and functioning also indicated, on the whole, good current functioning. No significant relationship was found between stage of medical illness or immune status and any measure of psychiatric disturbance.