Posttraumatic stress, depression, and health among older adults in primary care.

OBJECTIVE: The authors examined 1) rates of trauma and posttraumatic stress (PTS) in older adults in primary care; 2) factors related to more posttraumatic stress symptoms; and 3) the influence of posttraumatic stress and depression on health perceptions and negative health behaviors (i.e., suicidal ideation, smoking, and at-risk drinking). METHODS: As part of participation in a study at the Philadelphia VAMC and the University of Pennsylvania, a random subset (N = 2,718) of older adults (age > or = 65 years) with scheduled primary care visits were screened concerning demographics, the General Health Questionnaire-12, suicidal thoughts, alcohol consumption, cigarette smoking, perceived health status, PTS, and cognitive impairment. RESULTS: The rate of trauma in older adult primary care patients was high in both the VA (37%) and university-based clinics (24%). Many older adults reported interference from at least one of the three posttraumatic stress items assessed (VA, 18%; university-based primary care, 8%). In a model including demographic factors, higher PTS and depression were uniquely related to more negative health perceptions. In a model including demographic factors, both higher PTS and depression were uniquely related to higher likelihood of suicidal ideation. In contrast, PTS no longer contributed to a model of smoking once depression was included. Neither PTS nor depression significantly contributed to a model of at-risk drinking. CONCLUSIONS: Trauma and posttraumatic stress are frequent and significant problems for older adults in primary care. Both posttraumatic stress and depression are related to more negative health perceptions and higher likelihood of suicidal ideation.     

Influence of parainfluenza-1 respiratory tract viral infection on endothelin receptor-effector systems in mouse and rat tracheal smooth muscle.

1. In this study we have compared the effects of parainfluenza-1 respiratory tract viral infection on the density and function of ETA and ETB receptors in rat and mouse tracheal airway smooth muscle. 2. The bronchoconstrictor effect of inhaled methacholine was significantly enhanced in virus-infected rats, at both 4 and 12 days post-inoculation. That is, the concentration of methacholine causing an increase in resistance of 100% (PC100 methacholine) was significantly lower in virus-infected animals at both 4 and 12 days post-inoculation (n = 6-8; P < 0.05). 3. Total specific binding of [125I]-endothelin-1 and the relative proportions of ETA and ETB binding sites for [125I]-endothelin-1 were assessed in tracheal airway smooth muscle in parainfluenza-1-infected rats and mice at days 2, 4 and 12 post-inoculation using the ligands BQ-123 (1 microM; ETA receptor-selective) and sarafotoxin S6c (100 nM; ETB receptor-selective). Total specific binding in mice was significantly reduced at day 2 post-inoculation (n = 5; P < 0.05) but not at days 4 and 12 post-inoculation (n = 5). In control mice, the proportions of ETA and ETB binding sites were 53%:47% at day 2 and 43%:57% at day 4 and these were significantly altered by parainfluenza-1 infection such that, the ratios were 81%:19% at day 2 and 89%:11% at day 4 (P < 0.05). By day 12 post-inoculation, the proportion of ETA and ETB binding sites in tracheal smooth muscle from mice infected with parainfluenza-1 was not significantly different from control. In rat tracheal airway smooth muscle, neither total specific binding nor the ETA and ETB binding site ratio (64%:36%) were significantly altered in virus-inoculated rats at days 2, 4 or 12 post-inoculation (n = 5). 4. Parainfluenza-1 infection in mice had no effect on the sensitivity or maximal contractile effect of endothelin-1 in tracheal smooth muscle at days 2, 4 or 12 post-inoculation (n = 4). In contrast, contraction in response to the ETB receptor-selective agonist sarafotoxin S6c was attenuated by 39% at day 2 and by 93% at day 4 post-inoculation (P < 0.05). However, by day 12 post-inoculation, contractions to sarafotoxin S6c were not significantly different between control and virus-infected mice. In parainfluenza-1-infected rats, there were small but significant reductions in the sensitivity to carbachol, endothelin-1 and sarafotoxin S6c whilst the maximal responses to the highest concentrations of these agonists were not significantly altered by virus infection (n = 8). 5. BQ-123 (3 microM) had no significant effect on cumulative concentration-effect curves to endothelin-1 in tracheal preparations from control mice (n = 4) or parainfluenza-1-infected rats (n = 8). In contrast, in tissues taken from virus-infected mice at day 4 post-inoculation, BQ-123 caused a marked 9.6 fold rightward shift in the concentration-effect curve to endothelin-1 (n = 4). 6. In summary, we have demonstrated that parainfluenza-1 infection in mice transiently reduced the density of tracheal airway smooth muscle ETB receptors and this was reflected in reduced responsiveness to the ETB receptor-selective agonist sarafotoxin S6c. In contrast, whilst parainfluenza-1 infection in rats was associated with the pathological features and bronchial hyperresponsiveness common to respiratory tract viral infection, there was no selective down-regulation of ETB receptor expression or functional activity. The reasons for these species differences are not clear, but may relate to differences in the airway inflammatory response to parainfluenza-1 virus.     

Temporal segmentation of response speed in depression: neuro-electrophysiological approaches

1. Depressive psychomotor retardation, as observed by delayed reaction times (RT), may be related to a slowing in information processing speed. 2. Two separate studies compared indices of information processing speed in depressed patients and non-clinical controls by segmenting behavioral RT with brain event-related potentials (ERPs) and electromyographic (EMG) responses. 3. In Study I, slower behavioral RTs in depression were concomitant with slower central processing times (CPT) but not motor execution times (MET). 4. In Study II, P165, a putative early cognitive ERP related to 'stimulus evaluation time', was found to be slower but within normal range in depressed patients.     

REPAIR AND RECOVERY FOLLOWING SPINAL CORD INJURY IN A NEONATAL MARSUPIAL (MONODELPHIS DOMESTICA)

1. Repair and recovery following spinal cord injury (complete spinal cord crush) has been studied in vitro in neonatal opossum (Monodelphis domestica), fetal rat and in vivo in neonatal opossum. 2. Crush injury of the cultured spinal cord of isolated entire central nervous system (CNS) of neonatal opossum (P4–10) or fetal rats (E15–E16) was followed by profuse growth of fibres and recovery of conduction of impulses through the crush. Previous studies of injured immature mammalian spinal cord have described fibre growth occurring only around the lesion, unless implanted with fetal CNS. 3. The period during which successful growth occurred in response to a crush is developmentally regulated. No such growth was obtained after P12 in spinal cords crushed in vitro at the level of C7–8. 4. In vivo, in the neonatal (P4–8) marsupial opossum, growth of fibres through, and restoration of, impulse conduction across the crush was apparent 1–2 weeks after injury. With longer periods of time after crushing a considerable degree of normal locomotor function developed. 5. By the time the operated animals reached adulthood, the morphological structure of the spinal cord, both in the region of the crush and on either side of the site of the lesion, appeared grossly normal. 6. The results are discussed in relation to the eventual longterm possibility of devising effective treatments for patients with spinal cord injuries.     

Differential effects of interleukin-1α and β on the arachidonic acid cascade in human synovial cells and chondrocytes in culture

The effects of interleukin-1 and were tested on the [³H]-arachidonic acid release and the prostaglandin synthesis by human cultured synovial cells and chondrocytes. Both forms of interleukin-1 stimulated the arachidonic acid release but interleukin-1 was more potent than IL-1. Human synovial cells and chondrocytes synthesized three types of prostaglandins upon stimulation with interleukin-1 or : prostaglandin E₂, F₂ and 6-keto-prostaglandin F₁. Regarding the synthesis of these prostaglandins, IL-1 was again more potent than IL-1. A comparison between interleukin-1-stimulated synovial cells and chondrocytes revealed neither significant quantitative nor qualitative differences in both the arachidonic acid release and the prostaglandin synthesis.     

Sensitivity of the Procleix HIV-1/HCV assay for detection of human immunodeficiency virus type 1 and hepatitis C virus RNA in a high-risk population

The Procleix HIV-1/HCV Assay is a high-throughput nucleic acid test for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA during blood donor screening. This study evaluated the clinical sensitivity of the Procleix assay and assessed the assay's ability to identify HIV-1- and HCV-infected individuals undetected by standard serologic tests. Plasma samples were obtained prospectively from 539 individuals at high risk for HIV-1 and HCV infection at seven clinics affiliated with Johns Hopkins University. Samples were tested in the Procleix HIV-1/HCV Assay and, if reactive, were then tested in the Procleix HIV-1 and HCV discriminatory assays to differentiate the source of viral RNA positivity. Of these 539 subjects, 287 (53.2%) tested reactive in the Procleix HIV-1/HCV Assay. In discriminatory assay testing, 12 of 287 subjects (4.2%) were reactive for HIV-1 RNA only, 260 (90.6%) were reactive for HCV RNA only, and 11 (3.8%) were coinfected with HIV-1 and HCV. The clinical sensitivity for samples tested neat was 100% for HIV-1 and 99.3% for HCV. Three subjects with Procleix HCV reactive/seronegative results seroconverted upon follow-up and were confirmed as Procleix HCV yield cases. The Procleix HIV-1/HCV Assay is a highly sensitive test that detects ongoing and early HIV-1 and HCV infection in a significant number of subjects at high risk for these diseases. Confirmation of Procleix yield cases upon follow-up demonstrated the ability of the Procleix HIV-1/HCV Assay to detect the presence of HIV-1 and HCV in blood earlier than standard serologic tests.     

Will immunogenicity limit the use, efficacy, and future development of therapeutic monoclonal antibodies?

While monoclonal antibodies show promise for use in the treatment of a variety of disease states, including cancer, autoimmune disease, and allograft rejection, generation of anti-antibody responses still remains a problem. For example, 50% of the patients who receive OKT3 produce blocking antibodies that interfere with its binding to T cells, thus decreasing the therapeutic effect (51). HAMA responses have also interfered with tumor imaging (39,40) and radioimmunotherapy (56). The generation of an anti-antibody response is dependent on many factors. These include the dose of antibody, the number of injections of antibody, the immunogenicity of the antibody, the form of the antibody, and the immunocompetence of the recipient. Predictably, both the number of injections of antibody and the dosage are influential in the generation of an anti-antibody response. It is apparent that human antibodies, chimeric antibodies, and mouse Fab fragments are much less likely to induce anti-antibody responses than intact mouse monoclonal antibodies or mouse F(ab')2 fragments when one injection is administered. Injections of human or chimeric antibodies appears to reduce immunogenicity, but the probability that anti-antibody responses can still be induced on multiple injections must be considered and appropriately evaluated. Several areas demand extensive investigation to enhance the clinical utility of monoclonal antibodies. First, results of thorough clinical trials with human or chimeric antibodies need to be evaluated for the induction of anti-antibodies after multiple injections of antibodies. Second, less immunogenic forms of antibodies (Fab, Fv) need to be studied for their clinical efficacies and for their abilities to induce anti-antibody responses.     

CORTICAL SLOW POTENTIAL CHANGES IN MAN RELATED TO INTERSTIMULUS INTERVAL AND TO PRE TRIAL PREDICTION OF INTERSTIMULUS INTERVAL

Two experiments were performed to explore further the relationship between the cortical slow potential change known as the “contingent negative variation” (CNV) and the concept of “expectancy.” In Experiment I, 24 male Ss were presented click pairs, with inter-click intervals of 800, 1600 and 4800 msec (2 blocks of 10 trials each, counterbalanced between Ss for order), and instructed to press a key after the second click. Interval by order by trials analysis of variance showed interval to be the only significant factor: CNVs were lower and RTs longer as interval increased. In Experiment II, 8 female Ss given 60 pairs of clicks, 30 each with separations of 1200 and 2400 msec, were instructed to respond as in Experiment I, and were asked to make a pretrial prediction of the interval they would next receive. Analysis of variance of RTs showed that Ss responded slower when the interval was other than that predicted. Prediction by reception by subjects analysis of variance of CNV amplitude at the 1200 msec point gave a significant F only for prediction, mean amplitude for short being higher than for long. A similar design applied to CNV amplitudes at both the 1200 and 2400 msec points when Ss received the long interval yielded a significant measurement point by interval predicted interaction; at the 1200 msec point, short predictions were followed by higher CNVs than were long predictions; at 2400 msec, the opposite was found. These data combine with those already in the literature to indicate that the relationship between “expectancy” and the CNV is far from simple, and that cognitive and motivational factors play a significant role in determining CNV amplitude.     

Impact of an organ donor and tissue donor advocacy program on community hospitals

A crucial shortage of organ donors exists in the United States. The majority of donor referrals come from large (greater than 500) beds) hospitals and trauma centers. To determine whether a significant number of donors who are not being recognized or referred also existed in medium-sized (300 beds) community hospitals, a Donor Advocacy Program was instituted at Francis Scott Key Medical Center in May 1987. This team developed policies and procedures to identify potential donors and conducted educational programs for physicians and nurses. A designated "Donor Advocate" made daily rounds on the inpatient units to maintain donor awareness and facilitate potential donations. After the first year, the program was evaluated. In comparison to the average of the previous three years, donor referrals increased by approximately 400 per cent and tissue donations increased over 500 per cent. Four organs were retrieved from two donors. It is concluded that an increase in referrals and tissue donations can be achieved at community hospitals through a structured donor awareness program. Recommendations are made to further examine the age group most often eligible for organ and tissue donations in community hospitals and target educational efforts accordingly. Commitment of hospital administration is vital to a positive outcome in such a program.