Biomedical subjects

S J Gibson

Publications and source records attributed to S J Gibson.

At least 37 records · Page 2Linked to original sources

PubMed1996

The effect of age on A delta- and C-fibre thermal pain perception.

It has been suggested that ageing may have a differential effect on C fibre-mediated protopathic/tonic pain versus epicritic/phasic pain perception mediated by A delta fibres. The present study attempted to independently assess age-related changes in the function of A delta- and C-nociceptive fibres by examining CO2 laser-induced thermal pain thresholds before, during and after a compression block of the superficial radial nerve in 15 young and 15 healthy elderly adult subjects. Nerve block efficacy was monitored via measures of cold, warm and mechanical threshold, and simple reaction time. During nerve compression block, reaction time and mechanical threshold increased, cold sensation became impaired while warm sensation remained unaffected throughout the test in both groups. With respect to pain sensitivity, young adults exhibited significant increases in thermal pain threshold during A-fibre block while pain threshold remained relatively stable across the 3 test periods in the elderly group. It would appear that elderly adults rely predominantly on C-fibre input when reporting pain whereas younger adults utilise additional input from A delta fibres. Subsequent analysis revealed that during pre- and post-block periods, older adults exhibited a significant elevation in thermal pain threshold; however, when A delta-fibre function was impaired and only C-fibre information was available, both groups responded similarly. These findings support the notion of a differential age-related change in A-fibre-mediated epicritic pain perception versus C-fibre-mediated protopathic pain.

Adult↗

PubMed1996

Fear of falling revisited.

OBJECTIVE: To evaluate the measurement properties of an expanded version of the Falls Efficacy Scale (FES)-a measure of fear of falling. The original FES measures fear on almost exclusively indoor activities, which may limit the usefulness of the scale in identifying early stages of fear of falling in active community-dwelling older people. DESIGN: Two-group convenience sample. SETTING: An outpatient referral clinic, and community-dwelling older people recruited from various sources. SUBJECTS: A volunteer sample of 111 healthy community-dwelling elderly (mean age 74.0 years) and a sample of 68 older people referred to a Falls and Balance Clinic (FBC) (mean age 79.2). Twenty-one subjects (9 healthy elderly and 12 FBC patients) were tested twice 1 week apart to investigate retest reliability. MAIN OUTCOME MEASURES: A 14-activity questionnaire (the Modified Falls Efficacy Scale [MFES]) was used that incorporated the original 10-activity FES and four additional activities. Falls efficacy was rated on a 10-point visual analogue scale for each activity. RESULTS AND CONCLUSIONS: The MFES demonstrated high internal consistency (Cronbach's alpha.95) and less skew than the original FES (-2.4 and -3.3, respectively). Factor analysis of the MFES revealed two factors accounting for 75% of the sample variance, grouping into an "indoor type activity" factor and an "outdoor type activity" factor. Retest reliability for the MFES was high (intraclass correlation coefficients = .93). Significant differences were evident between the FBC group and the healthy older group on all items of the MFES and on the total MFES score (p < .05). On the basis of these preliminary findings, the MFES appears to be a reliable and valid measure of falls self-efficacy, and could be a useful addition in the comprehensive assessment of older people with balance disturbance or falls.

Accidental Falls↗

PubMed1996

Measuring the activity of older people with chronic pain.

OBJECTIVE: A variety of instruments have been applied to the measurement of activity, yet few, if any, have been validated specifically for older people with chronic pain. This study has sought to examine the utility of the Human Activity Profile (HAP) for describing activity in a sample drawn from a pain clinic for older people. DESIGN: The HAP was administered to 193 older pain clinic patients, 72 of whom completed the profile on a second occasion. A further 55 responses were collected from a group of community-dwelling volunteers. The factor structure of the HAP was tested using these 320 responses. The factors subsequently derived were compared with the Sickness Impact Profile (SIP) and the Barthel Index (BI). The discriminant validity of the HAP was examined by comparing factor scores for groups determined by gender, diagnosis, and status in the pain clinic. RESULTS: The 94 items of the HAP loaded onto 10 factors, which explained 63.7% of the variance. These factors demonstrated moderate associations with the BI and the subscales of the SIP. The factors discriminated between men and women (F[12.180] = 9.85. p < 0.000). Differences were also present between subjects with a musculoskeletal pain problem, postherpetic neuralgia, and pain-free volunteers (F[24.340] = 4.7. p < 0.000). Factor scores increased between pre- and postclinic assessments (F[12.60] = 4.79. p < 0.000). CONCLUSIONS: The HAP has demonstrated qualities which favor its adoption as an activity measure for older pain clinic patients.

Aged↗

PubMed1996

Multidisciplinary pain clinics for older people. Do they have a role?

Chronic pain occurs frequently in older people but is rarely considered a problem which warrants specialized attention by physicians or specialists in pain management. However a small proportion of older people with significant psychologic and physical disability from pain fail to respond to conservative management strategies. In this article, the authors describe the operations of a successful multidisciplinary pain management center for older people and briefly outline outcomes according to measures of pain, mood, and activity. Other factors that are specific and important to the management of chronic pain in older patients are discussed also. Despite some disadvantages, it is concluded that there is a place for multidisciplinary pain clinics for older people.

Aged↗

PubMed1995

Cytokine induction by the immunomodulators imiquimod and S-27609.

Imiquimod (R-837, S-26308) and the analogue S-27609 were evaluated for cytokine induction in human blood cells. Both compounds induced interferon-alpha (IFN), tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 with S-27609 being 5 to 10 times more potent. Imiquimod and S-27609 also induced IL-1 alpha, IL-1 receptor antagonist, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and macrophage inflammatory protein-1 alpha. The profile of cytokines induced by imiquimod and S-27609 was different from those seen with lipopolysaccharide and polyinosinic-polycytidylic acid. Kinetic studies with both imiquimod and S-27609 revealed induction of cytokines as early as 1-4 h after stimulation. Although most of the cytokines produced by S-27609 were secreted, significant concentrations of IL-1 alpha and IL-1 beta remained intracellular. Monocytes were largely responsible for the cytokines produced. Finally, S-27609-induced mRNA expression for TNF, IFN, and IL-8, and this induction did not require protein synthesis. Taken together, these studies extend previous findings by showing induction of additional cytokines and providing insight into the mechanism of cytokine induction by these molecules.

Adjuvants, Immunologic↗

PubMed1995

Immunomodulating and antiviral activities of the imidazoquinoline S-28463.

Recently, a new class of immunomodulating agents, represented by the molecules imiquimod and R-842, has demonstrated potent antiviral and antitumor activities in animal models. In this study, another representative of this class, S-28463 (4-amino-2-ethoxymethyl-alpha,alpha-dimethyl-1H-imidazo[4,5-c]quinoline- 1- ethanol) was evaluated for its immunomodulating and antiviral activities. S-28463 induced IFN and other cytokines in vivo in mice, rats, monkeys and in vitro in human peripheral blood mononuclear cell cultures. S-28463 showed potent antiviral activity against herpes simplex virus-challenged guinea pigs when given subcutaneously, dermally, or intravaginally 24 h before infection. Antiviral activity in guinea pigs correlated with the induction of serum 2',5'-oligoadenylate synthetase activity. Thus, S-28463, like the other imidazoquinolines, demonstrates potent antiviral and immunomodulating effects in a number of models.

2',5'-Oligoadenylate Synthetase↗

PubMed1995

Cellular requirements for cytokine production in response to the immunomodulators imiquimod and S-27609.

Imiquimod (R-837) and its analog, S-27609, belong to a class of imidazoquinolinamines that have potent antitumor and antiviral effects in animals. Much of their biologic activity is a result of the induction of cytokines, including interferon-alpha (IFN-alpha), tumor necrosis factor alpha (TNF), and others. In this study, the cells responsible for S-27609- and imiquimod-induced cytokine production were characterized. E rosette+ T cells were not the major cell population responsible for IFN-alpha and TNF in response to S-27609 or imiquimod. In contrast, E rosette- cells and unseparated PBMC produced similar concentrations of IFN-alpha and TNF in response to S-27609 and imiquimod. Elimination of monocytes by treatment with the lysosomotropic agent L-leucine methyl ester (LME) or depletion using antibody to CD14 and immunomagnetic beads abrogated IFN-alpha and TNF production induced by S-27609, imiquimod, or LPS but not poly(I)/(C). LME treatment also abolished interleukin (IL)-1 alpha, IL-beta, IL-6, and IL-8 production stimulated by S-27609 and imiquimod. Removal of HLA-DR+ or CD36+ monocytes also caused a significant reduction in S-27609- and imiquimod-induced IFN-alpha and TNF. Elimination of B cells, NK cells, and dendritic cells did not significantly reduce cytokine induction in response to S-27609. Thus, the cell population responsible for the majority of cytokine release in human PBMC in response to S-27609 and imiquimod is a E rosette-, CD14+, CD36+, HLA-DR+ monocyte.

Adjuvants, Immunologic↗

PubMed1995

The effect of medical status on the activity level of older pain clinic patients.

OBJECTIVE: This project sought to assess the effect of disease status on the activity level of older people suffering from chronic pain. DESIGN: A retrospective comparison of groups defined by disease attributes. SETTING: Outpatient pain management clinic for older people. SAMPLE: The sample consisted of 115 patients, of a possible 144, aged between 52 and 91 years, who were assessed upon admission to a multidisciplinary pain management clinic. Subjects were allocated to groups for comparison on the basis of the diagnosis of their pain problem and the extent of coexistent medical problems. MEASUREMENTS: Groups were compared on scores of activity level using the Human Activity Profile, with and without pain (McGill Pain Questionnaire) and depressive symptom (Geriatric Depression Scale) scores as covariates. MAIN RESULTS: Both pain diagnosis and number of additional medical problems characterized groups that were distinguishable by level of activity. A musculoskeletal disorder was associated with greater impact on activity than either postherpetic neuralgia or pain associated with a psychiatric diagnosis. Less activity was also evident among the subjects with several additional medical problems. However, this effect did not operate independently of depressive symptoms. CONCLUSIONS: Disease status is a factor that rarely explains variations in the pain experience of young adult patients with chronic pain. The results from this study suggest that disease state does influence self-reported activity level in older people with chronic pain. The influence of medical status should be acknowledged as an important factor when assessing and managing the older patient with chronic pain.

Activities of Daily Living↗

PubMed1994

Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome.

A decrease in mechanical pressure pain thresholds, particularly over pre-designated tender points, is one of the defining characteristics of fibromyalgia syndrome (FS); however, changes in thermal pain sensitivity have not been investigated. The present study examined heat pain thresholds and cerebral event-related potentials following CO2 laser stimulation in 10 subjects with FS and 10 age-matched control volunteers. The results indicate that patients with FS exhibit a significant reduction in heat pain threshold when tested on the dorsal surface of the hand. In accordance with previous research, we also found a decrease in mechanical pain threshold over pre-designated tender points and at control sites as well as a significantly larger mechanically induced neurogenic flare response. These measures were highly correlated with thermal pain threshold even though different anatomical sites were stimulated. Hence, it seems likely that FS patients display a multimodal change in pain sensitivity which is generalized rather than anatomically restricted. Patients with FS also displayed a significant increase in the peak-to-peak amplitude of the cerebral potential evoked by CO2 laser stimulation at pain threshold intensity and 1.5 times pain threshold intensity. These findings suggest a greater activation of central nervous system (CNS) pathways following noxious input. Putative explanations for the increased CNS response are discussed, including mechanisms of peripheral nociceptor sensitization, altered CNS function and the role of psychological factors.

Adult↗

PubMed1994

Induction of interferon and other cytokines by imiquimod and its hydroxylated metabolite R-842 in human blood cells in vitro.

The low-molecular-weight immunomodulator drug candidate, imiquimod (R-837), and its hydroxylated metabolite R-842, induce interferon-alpha (IFN-alpha) in human blood cells in vitro when tested in concentrations of 0.5 microgram/ml or more. The amounts of IFN-alpha found increased with time from 2-6 h of incubation up to 24-48 h, and were dependent on cell number and drug concentration. These two chemicals yielded more IFN-alpha in human peripheral blood mononuclear cell (PBMC) cultures than other known inducers tested in parallel. They also induced detectable amounts of interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha in human PBMC cultures in vitro.

Aminoquinolines↗

PubMed1994

CNS-directed case management. Cost and quality in harmony.

Preserving the integrity of high quality care in a financially restricted environment is the primary challenge facing healthcare providers. The critical question is which delivery system will use limited resources most efficiently without jeopardizing quality of care? Case management has been identified as a solution that offers the most promise. The case management model at Sioux Valley Hospital was developed to deal proactively with resource-intensive patients with chronic illnesses who have frequent admissions and who create financial risk for the hospital. The authors describe the fiscal and clinical outcomes of these select patients.

Adolescent↗

PubMed1994

The influence of clinical problems, age and social support on outcomes for elderly persons referred to regional aged care assessment teams.

BACKGROUND: Aged Care Assessment Teams (ACATs) have been established throughout Australia during the past seven years. Early studies of their effect have concentrated on their impact on the rate of institutionalisation of disabled elderly, the clinical characteristics of referred cases and the relationship between disability and recommended care plan. AIMS: The aim of this study was to explore the relationship between age, clinical features and social characteristics of ACAT subjects with outcomes at 12 months after assessment. METHODS: The examination of an arbitrary sample of persons referred to ACATs over a year by one generalist geriatrician with follow-up of all cases by the three ACATs associated with the study was carried out. All analyses were performed on raw data presented as categorical variables in the form of contingency tables. RESULTS: The sample included 324 subjects who suffered from 2030 clinical problems with a mean of 6.5 per person aged 75 or over and 5.5 for those under 75. Cardiovascular and neurological disease were the commonest source of problems. Study of accommodation outcome at 12 months, for those subjects who survived this period revealed that, in the older group, over 60% of subjects with neurological disease were resident in nursing homes while the majority of all other groups remained in the community, as did two-thirds of those aged under 75. Admission to a nursing home was independent of social support for older subjects with neurological disease, but it played a significant role in those with cardiopulmonary or musculoskeletal disease. CONCLUSIONS: The study demonstrates that for one-year survivors there is an increased likelihood of admission to a nursing home of people aged 75 or over with neurological disease, while those under 75 were more likely to remain at home. The association was independent of whether spouse, family or friends were living with the subject.

Adult↗

PubMed1992

Morphological basis for back pain: the demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum.

The innervation of lumbar facet capsule and ligamentum flavum was investigated using antisera to a general neuronal marker protein gene product (PGP) 9.5 and to peptide markers of sensory nerves (calcitonin gene-related peptide [CGRP] and substance P) and autonomic nerves (vasoactive intestinal polypeptide [VIP] and C-flanking peptide of neuropeptide Y [CPON]). In the facet capsule (n = 14), PGP 9.5 and CGRP-immunoreactive nerves occurred in 12 and five specimens, respectively, both around blood vessels and as free fibers in the stroma. Free fibers immunoreactive for substance P or VIP were noted in three and five specimens, whereas in nine specimens there were CPON-immunoreactive nerves located perivascularly. There was no immunoreactivity in the ligamentum flavum. This study provides further evidence that the facet capsule but not the ligamentum flavum has substantial innervation by sensory and autonomic nerve fibers and has a structural basis for pain perception.

Adult↗

PubMed1992

Transient expression of neuropeptide Y and its C-flanking peptide immunoreactivities in the spinal cord and ganglia of human embryos and fetuses.

An immunohistochemical study of spinal cord, dorsal root and sympathetic ganglia of human embryos and fetuses demonstrated that neuropeptide Y and its C-flanking peptide could be detected in seven-week-old embryos but were absent or difficult to demonstrate after the 17th week of gestation. The peptides were found in several structures of the spinal cord, e.g. fibres in the dorsal portion of the lateral funiculus, cell bodies and fibres in the dorsal horn, and motoneurons, and also in numerous primary sensory neurons of dorsal root ganglia. They were also present in sympathetic neurons and since these are the only structures expressing neuropeptide Y and its C-flanking peptide in the adult, it must be concluded that their presence in other neurons is a transient developmental feature. To assist in understanding the relationship of these transient structures with other spinal and sensory neurons, a comparison was made with other neuronal structures showing immunoreactivity for two general neuronal markers, neurofilaments and protein gene product 9.5, and two neuropeptides present in primary sensory afferents, somatostatin and substance P. In the dorsal root ganglia, numerous neuropeptide Y- and C-flanking peptide-immunoreactive neurons were observed before substance P- or somatostatin-immunoreactive cells could be detected. Therefore, neuropeptide Y and its C-flanking peptide could represent a primitive peptidergic system appearing before primary sensory neurons express their characteristic adult phenotype. The fibres of the lateral funiculus showing immunoreactivity for neuropeptide Y and its C-flanking peptide were longitudinally orientated and could be detected at all cephalocaudal levels of the spinal cord. Comparison with the other immunohistochemical markers indicated that they were not primary sensory afferents. At least some of them probably originated from neuropeptide Y- and C-flanking peptide-immunoreactive neurons of the dorsal horn, that may be considered to be a subset of early-appearing interneurons.

Embryo, Mammalian↗

PubMed1992

Intracellular redistribution of neuropeptides and secretory proteins during differentiation of neuronal cell lines.

We have demonstrated that the mouse neuroblastoma N18Tg2 cell line and several clones of hybrid ND cells (ND7, ND9 and ND21), derived from the fusion of neonatal rat sensory neurons with that neuroblastoma, show immunostaining to protein gene product 9.5, neuropeptide Y, C-flanking peptide of neuropeptide Y, tyrosine hydroxylase and chromogranins. Synaptophysin could only be detected in ND cells. Immunoreactivities to substance P, calcitonin gene-related peptide, galanin and somatostatin could not be detected in any of these cell lines. After three days of incubation in a differentiation medium, cell processes of various lengths were observed both in neuroblastoma and ND cell cultures. In ND7 cells there was also a redistribution of neuropeptide Y and its C-flanking peptide to the tips of cell processes. The differentiation of cell processes was also accompanied by the appearance of immunostaining to rat chromogranins in their tips. In contrast, synaptophysin expression was found mainly in cell bodies. Neuropeptide Y, its C-flanking peptide and chromogranins have been associated with secretory granules, whereas synaptophysin is a marker for small synaptic-like vesicles. Therefore, our morphological findings further support and expand the view that these markers are primarily associated with different subcellular structures. Moreover, they indicate that the regulated secretory pathway associated with chromogranins is segregated into nerve processes at an early stage of differentiation, when the synaptophysin-associated pathway is not yet mature. ND7 cells thus provide a useful model system for studying changes in the distribution of neuropeptides, cytoskeletal elements and proteins associated with cell secretion during neuronal differentiation.

Animals↗

PubMed1992

RSI revisited: evidence for psychological and physiological differences from an age, sex and occupation matched control group.

The present study sought to examine psychological characteristics and function of primary afferent nociceptive mechanisms, as indexed by capsaicin-induced flare responses, in subjects suffering from RSI (n = 72) and in pain free control volunteers (n = 69). After completing a battery of psychological tests including the McGill Pain Questionnaire, Visual Analogue Scale and Word Descriptor Scale for pain, the Profile of Mood States, Illness Behaviour Questionnaire and Multidimensional Health Locus of Control, the neurogenic flare response was assessed on the right and left forearms and across the trapezius at the shoulder. When compared to controls RSI subjects displayed higher levels of mood disturbance and some abnormal patterns of illness behaviour. A reduction in flare size was observed in the pain affected limb of RSI subjects, but an increased response occurred in sites reported as unaffected by clinical pain. Multiple regression analysis revealed that the severity of clinical pain was strongly associated with the magnitude of reduction in flare size. Collectively, these findings provide objective evidence of altered nociceptor mechanisms in RSI subjects, and are consistent with the view that this chronic pain syndrome involves somatic pathophysiology. However, a strong conviction regarding the somatic basis of their symptoms, and a denial of psychological factors may have contributed to the more severe affective disturbance and greater subjective emphasis on the presence of pain.

Affect↗

PubMed1992

Innervation of bone from healthy and arthritic rats by substance P and calcitonin gene related peptide containing sensory fibers.

Mechanical stress causes remodelling of bone, a transformation of bone structure by physical forces through an unknown mechanism. Inflammation also affects bone structure, through altered use and the production of various inflammatory mediators. The peripheral nervous system may play both a sensory and an efferent role in the mechanical and inflammatory influences on bone structure. We studied the occurrence of substance P and calcitonin gene related peptide (CGRP) containing nerves in periosteal tissue, bone marrow, diaphysis and epiphysis of the ankle and knee joints of healthy and adjuvant arthritic rats. In arthritic animals, only ankle joints were affected by the inflammation. The periosteum was richly innervated both in healthy and arthritic animals. In arthritic rats few nerve fibers penetrated the woven, callous bone underlying the periosteum. Also bone marrow contained substance P and CGRP immunoreactive nerves in normal bone, whereas the hypercellular bone marrow of arthritic rats showed a decrease in the density of substance P and CGRP containing fibers. Epiphysis had a dense innervation compared to diaphysis. In contrast to large erosions, small peripheral erosions contained some CGRP immunoreactive fibers, perhaps as a sign of attempts of reactive repair. Our results suggest a local delivery system of potent peptide regulatory factors in bone, a system also affected by the pathophysiology of arthritis.

Animals↗

PubMed1991

Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain.

The distribution of endothelin mRNA and immunoreactivity in the human brain was investigated using the technique of in situ hybridization and immunocytochemistry. Cryostat sections from 22 cases of neurologically normal adult human brain, collected 3-7 h post-mortem were hybridized with 35S-labelled complementary (c)RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization with all three cRNA probes revealed labelled neuronal cell bodies in laminae III-VI of the parietal, temporal and frontal cortices. Labelled cells were also seen, scattered throughout the para- and periventricular, supraoptic and lateral hypothalamic nuclei, the caudate nucleus, amygdala, hippocampus, basal nucleus of Meynert, substantia nigra, raphe nuclei, Purkinje cell layer of the cerebellum and in the dorsal motor nuclei of the vagus of the medulla oblongata. The distribution of neurones immunoreactive to endothelin was similar to that of endothelin mRNA, although fewer immunoreactive cells throughout the brain, were noted. Immunoreactive fibres were present mainly in the cortex and hypothalamus, and to a lesser extent in the brain stem. Combined in situ hybridization and immunocytochemistry on the same section revealed the presence of endothelin-1 mRNA and immunoreactivity in the same cortical neuronal cell. Colocalisation studies in the cortex revealed endothelin-1 mRNA and immunoreactivity in a number of cells which also expressed neuropeptide Y mRNA and immunoreactivity. In the hypothalamus and basal nucleus of Meynert endothelin immunoreactivity was colocalised to a subset of neurophysin- and galanin-immunoreactive cell bodies respectively. Endothelin mRNA and immunoreactivity was also seen in some blood vessel endothelial cells. The findings of endothelin mRNAs and immunoreactivity in heterogenous neuronal populations further emphasises the potential role of endothelin as a neuropeptide, probably having diverse actions in the nervous system of man.

Adult↗