Biomedical subjects

R D Helme

Publications and source records attributed to R D Helme.

At least 37 records · Page 2Linked to original sources

PubMed1997

[The effect of endothelin and protein kinase C on the vasoactive mechanisms of beta A(4)25-35 at skin microvasculature].

OBJECTIVE: The aim of the present study is to investigate the mechanisms of beta A(4)25-35 at the level of skin microvascula ture. METHODS: Using a blister model in rat skin, we examined the possibilities that beta A(4)25-35 induces VC effect via the release of endothelin and the involvement of protein kinase C (PKC). Changes in microvascular blood flow were monitored using laser Doppler flowmetry and the area within the response curve measured. RESULTS: The results showed that either the endothelin receptor antagonist (BQ--123 at 10 mumol) or PKC inhibitor (bisindolylmaleimide at 1 mu mol) was perfused before beta A(4)25-35. It prevented beta A(4)25-35 from inducing a VC effect and allowed a subsequent SP to induce a normal response. CONCLUSION: Both endothelin and PKC play a role in the mechanism be which beta A(4)25-35 induces VC effect and modulates subsequent SP response at the level of skin microvasculature. We suggest the possibility that the vascular activity of beta A(4)25-35 could be mediated via endothelin with subsequent activation of PKC.

Alzheimer Disease↗

PubMed1996

Mechanisms underlying the vascular activity of beta-amyloid protein fragment (beta A(4)25-35) at the level of skin microvasculature.

Deposition of beta-amyloid protein (beta A4) in extracellular senile plaques is a pathologic hallmark of Alzheimer's disease (AD). The neurotoxic effect of beta A4 has been ascribed to a discrete 11-amino acid internal sequence (beta A(4)25-35). Substance P (SP) has been found to be depleted in the brain of AD patients while its presence was found to protect against the neurodegenerative effect of beta A(4)25-35. Our previous studies, in vivo, in aged rats showed that beta A(4)25-35 exhibits a potent vasoconstrictor (VC) effect in rat skin microvasculature and can prevent SP but not calcitonin gene-related peptide (CGRP) from inducing a vasodilator (VD) response. It was postulated that beta A(4)25-35 might be interacting with SP at the level of the second messenger system via the phosphoinositide pathway. Using a blister model of inflammation in the rat hind footpad, we examined the ability of beta A(4)25-35 to modulate the vascular activity of bradykinin (BK) and serotonin (5-HT) which also activate the phosphoinositide pathway. In addition, the role of nitric oxide (NO), endothelin (ET, an endothelium-derived constrictor factor) and protein kinase C (PKC) in the vascular effects of beta A(4)25-35 were examined using the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG), the ET-receptor antagonist, BQ-123, and the PKC inhibitor, bisindolylmaleimide (BIM) respectively. Changes in microvascular blood flow were monitored using laser Doppler flowmetry and the area within the response curve measured. The results showed that beta A(4)25-35 (10 microM) induced a VC effect and inhibited the subsequent VD response to BK (10 microM) and 5-HT (1 microM) in a similar fashion to its effect on SP (1 microM). In the presence of L-NOARG (100 microM), the VD effect of SP was reduced and further attenuated after perfusion of beta A(4)25-35. Superfusion of the blister base with BQ-123 (10 microM) or BIM (1 microM) prior to and during perfusion with beta A(4)25-35 abolished its VC effect and allowed SP to induce a normal VD response in both young and old rats. Based on these results, we suggest that the vascular activity of the active fragment, beta A(4)25-35, is mediated by ET via activation of PKC. This study provides new findings which may help to elucidate the signal transduction mechanisms involved in the vascular activity of beta A(4)25-35. The relevance of these mechanisms to those underlying the pathological effects of beta A4 and their significance in AD remains to be determined.

Aging↗

PubMed1996

Effect of chronic sciatic nerve lesion on the neurogenic inflammatory response in intact and acutely injured denervated rat skin.

A supersensitivity to the neuropeptide substance P (SP) has been shown to develop in post-terminal membranes of many denervated tissues. This study examined changes in the sensitivity of post-terminal vascular receptors to SP and calcitonin gene-related peptide (CGRP) in rat skin microvasculature following sciatic nerve section. In anaesthetised rats, 0.5 cm of sciatic nerve in the right mid-thigh region was removed. Two weeks later, SP (100 microM) and sodium nitroprusside (SNP, 1 mM), a direct smooth muscle vasodilator, were introduced into denervated intact footpad skin, via the electrophoresis technique. Laser doppler flowmeter was used to record changes in relative blood flow in the rat hind footpad. The results showed a significant increase in SP response over controls and slight increase in smooth muscle reactivity as determined by an increase in the vascular response to SNP. In another set of experiments, the sensitivity of post-terminal receptors was examined over a 4 weeks period in an acutely injured footpad skin of sciatic nerve lesioned rats. A vacuum-induced blister was raised on the hind footpad and SP, CGRP (each at 1 microM) or SNP (100 microM) were superfused over the blister base. In nerve lesioned rats, using the acutely injured footpad skin model, the results showed a reduction in the vascular responses to SP, CGRP and SNP. The response to SP continued to decrease over time reaching 22% of control values by 4 weeks. Responses to SNP and CGRP were reduced to 53% and 45% respectively by 2 weeks and then improved to 75% of control values by 4 weeks. Possible contributions of sympathetic efferents and the saphenous nerve to these reduced responses in acutely injured skin of nerve lesioned rats were examined using guanethidine (50 mg/kg i.p.) or sectioned saphenous nerve respectively. These procedures did not significantly modify the reduced vascular responses in the blister base of lesioned rats. Possible activation of endogenous opioids and/or the release of endothelin due to blister induction in nerve lesioned rats was examined using naloxone and the endothelin receptor antagonist, BQ-123, respectively. Treatment with naloxone increased SP response in lesioned rats to 41% of control value with no change in smooth muscle reactivity. BQ-123 significantly increased the responses to SP and SNP to 51% and 100% of their own control values respectively. It is concluded that supersensitivity of post-terminal vascular receptors develops in intact skin following chronic nerve lesion. On the other hand, acute injury of the denervated skin area induces activation of endogenous inhibitory modulatory mechanisms that masks this supersensitivity.

Anesthesia↗

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

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

Role of nitric oxide in the actions of substance P and other mediators of inflammation in rat skin microvasculature.

The role of nitric oxide in inflammatory responses to substance P and other mediators of inflammation was examined in rat skin microvasculature in a blister base raised on the hind footpad. Superfusion of substance P (1 microM) over the blister base caused an increase in plasma extravasation and a vasodilator response which was not maintained. N(G)-Nitro-L-arginine (100 microM), an inhibitor of nitric oxide biosynthesis, attenuated vasodilatation and plasma extravasation due to substance P. The inactive isomer N(G)-nitro-D-arginine was without effect. Neurokinin A (1 microM), 5-hydroxytryptamine (1 microM), ATP (50 microM) and vasoactive intestinal polypeptide (1 microM) elicited vasodilation, which for vasoactive intestinal polypeptide was maintained even after washout. 5-Hydroxytryptamine and neurokinin A, but not ATP or vasoactive intestinal polypeptide, significantly increased plasma extravasation. Vasodilatation to neurokinin A, 5-hydroxytryptamine and ATP, and the increase in plasma extravasation due to neurokinin A and 5-hydroxytryptamine were unaffected by N(G)-nitro-L-arginine (100 microM), whereas vasodilation due to vasoactive intestinal polypeptide was significantly attenuated. These findings suggest that in rat skin microvasculature in vivo, nitric oxide is involved in vasodilator responses due to substance P and vasoactive intestinal polypeptide, and plasma extravasation due to substance P, but does not contribute significantly to vasodilatation induced by neurokinin A, 5-hydroxytryptamine or ATP, or the plasma extravasation induced by neurokinin A or 5-hydroxytryptamine.

Adenosine Triphosphate↗

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↗

PubMed1995

Bone density, vitamin D nutrition, and parathyroid hormone levels in women with dementia.

OBJECTIVE: To determine whether patients with dementia have reduced bone mass, altered vitamin D, or parathyroid hormone status. DESIGN: Survey. SETTING: University hospital outpatient department. PARTICIPANTS: Twenty women with DSM-III-R mild dementia living in the community were compared with 40 cognitively normal community-dwelling women, matched for age, who had been recruited as part of studies in elderly twins. MEASUREMENTS: Bone density at the lumbar spine and neck of femur by dual-energy X-ray absorptiometry, intact serum PTH, and 25-hydroxyvitamin D levels. MAIN RESULTS: There was no significant difference in bone density between the subjects with mild dementia and the age- and sex-matched controls. The intact PTH (mean +/- SD) in the demented subjects was 4.9 +/- 2.1 pmol/L compared with 2.9 +/- 1.7 pmol/L in the twin controls (P < .01). The mean 25-hydroxyvitamin D in the demented subjects was 61 +/- 33 nmol/L, whereas it was 90 +/- 38 nmol/L in the twin controls (P < .01). CONCLUSIONS: We conclude that there were no significant differences in the bone density of community-dwelling women with mild dementia compared with normals. However, there were significant differences in parathyroid hormone and vitamin D levels between the two groups, suggesting that there is a high prevalence of subclinical hypovitaminosis D in demented women in the community.

Absorptiometry, Photon↗

PubMed1994

Effects of ageing on sensory nerve function in rat skin.

Human studies have shown an age-related decrease in modulation of skin vascular reactivity by sensory nerves that correlates with a decline in wound repair efficacy. Using a vacuum-induced blister model in the rat hind footpad, we have investigated age-related changes in pre- and post-terminal activity of primary afferents involved in skin neurovascular function. Changes in local skin blood flow were monitored using a laser Doppler flowmeter. Pre-terminal stimulation was achieved by electrical stimulation of the distal end of the sciatic nerve (10 V, 15 Hz and 0.5 ms) in three groups of young, old and neonatally pretreated capsaicin rats (3, 24 and 3 months old, respectively). The effect of post-terminal stimulation, achieved using local perfusion of 1 microM substance P (SP) over the blister base, was examined in young (3 months old), mature (12 months old) and aged (24 months old) rats. In addition to changes in SP responsiveness, other post-terminal changes studied included changes in smooth muscle reactivity to sodium nitroprusside (SNP), which acts directly on smooth muscle and to endothelial cell function using N-nitro-L-arginine (L-NORAG), a selective inhibitor of nitric oxide synthesis and endothelium-dependent relaxation. Electrical stimulation of the sciatic nerve in young rats induced an increase in local blood flow (within 1 min) that was maintained during the stimulation period, while the capsaicin group and the old group showed a significantly increased latency and decreased amplitude of the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

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

A falls and balance clinic for the elderly.

A Falls and Balance Clinic for the elderly has been developed with the aim of identifying those at risk of subsequent falls, and recommending intervention strategies to reduce this risk. The physical and functional status of 149 clients referred to the Clinic are reported. Neurological and musculoskeletal pathologies were identified as the cause of falls in the majority of clients. Measures of gait velocity and stride length, and ability to stand on one leg were markedly reduced compared with normative data for healthy elderly. A number of other measures of balance, strength, and function are also reported. The results of a questionnaire about home environment indicated that only 28% of those referred had been assessed in their own home in the previous year. Home environment was considered a potential risk in a further 28% of clients and a home visit was instituted in these cases. Other intervention strategies included referral for further investigations (36%), Day Hospital (33%), provision of a home program of balance or strengthening exercises (27%), and medication change (15%). Issues related to the establishment, operation and long term evaluation of the effectiveness of a specialist Falls and Balance Clinic for the elderly are discussed.

Accidental Falls↗

PubMed1993

Management of chronic pain.

The principles of chronic pain management in the elderly are the same as in younger people; whenever possible, the cause of the pain should be identified and eradicated. However, older people are more likely to suffer pain from incurable conditions, and the emotional component of the suffering may be considerable. Treatment options include analgesics, opiates, antidepressants and anticonvulsants as well as psychological strategies, physical strategies such as exercise and transcutaneous electrical nerve stimulation (TENS), and surgery. Improvement of function may be a more important treatment goal than relief of pain.

Aged↗

PubMed1993

In vivo inhibition of the rat primary antibody response to antigenic stimulation by somatostatin.

Somatostatin inhibits in vitro lymphocyte proliferative responses from a variety of species including human, mouse and rat. The immunoinhibitory effects of somatostatin are thought to involve binding to specific cell surface somatostatin receptors on immunocompetent cells. This report describes an in vivo immunoinhibitory effect of somatostatin on the rat popliteal lymph node lymphocyte primary antibody response to sheep red blood cell (SRBC) stimulation. Infusion of somatostatin immediately following SRBC injection into the hind feet of rats had a dose-related inhibitory effect. At the highest concentration used, 10 mumol/L, the level of inhibition was similar to that previously described following neonatal capsaicin treatment of rats. This suggests that neonatal capsaicin treatment may lead to decreased primary antibody responses to SRBC by a selective effect on tachykinin containing nerves and a lesser effect on somatostatin containing nerves. The immunoinhibitory effect of somatostatin was reversed by co-infusion of neurokinin A but not substance P, both of which have been shown to stimulate this response. This suggests the possibility that multiple tachykinin receptors are involved in the modulation of the SRBC primary antibody response in vivo. These results present evidence for an in vivo immunomodulatory role of somatostatin.

Adjuvants, Immunologic↗

PubMed1992

Students can learn medicine with computers. Evaluation of an interactive computer learning package in geriatric medicine.

OBJECTIVE: To assess the effectiveness of a computer-aided learning program on dementia. DESIGN: Fourth year medical students were arbitrarily assigned to groups that used a computer-aided learning program (65) or had a tutorial covering similar material (73). These sessions were in addition to a base curriculum in a two-week course in geriatric medicine. MAIN OUTCOME MEASURES: The effectiveness of the teaching sessions was judged by the performance on a multiple choice questionnaire about dementia, given to the students on two occasions, one at the beginning and one at the end of the two-week course. RESULTS: Both groups of students scored significantly better on the second test (computer group, 66% [95% confidence interval, 64-69] to 81% [79-83] and tutorial group, 66% [63-67] to 74% [73-77]). The difference between the groups at the start of the course was not significant (F1,136 = 0.61, P = 0.61); however, there was a significant difference between the groups at the end of the course (F1,136 = 21.83, P < 0.001). CONCLUSION: Both groups improved their knowledge of dementia during the two-week course. Students who used the computer-aided learning programs showed a greater improvement in score. Computer learning programs are effective learning tools and are a useful addition to traditional teaching methods. Further study is required to assess the effects of computer-aided learning programs in long-term studies of dementia knowledge.

Computer Literacy↗

PubMed1992

The quantitative contribution of nitric oxide and sensory nerves to bradykinin-induced inflammation in rat skin microvasculature.

Using a blister model in the rat hind footpad, the present study undertook to examine the relative contribution of sensory nerves and nitric oxide (NO) to the inflammatory response induced by bradykinin (BK). Using this model, combined with laser Doppler flowmetry, we were able to simultaneously monitor two parameters of the inflammatory response, namely vasodilatation (VD) and plasma extravasation (PE). Perfusion of BK (1, 10 or 100 microM) over the blister base elicited both VD and PE responses which were dose-dependent. The VD response was of rapid onset, sustained at the lowest concentration (1 microM), and showed tachyphylaxis at the highest two concentrations (10 and 100 microM). The PE response, however, was delayed in onset at the lower concentration but the response was maintained at all concentrations. The endothelium-independent vasodilator, sodium nitroprusside. (SNP, 100 microM), was used as an internal control and elicited a rapid maintained VD response. In rats pretreated as neonates with capsaicin to destroy primary sensory afferents, the inflammatory response to 10 microM BK was significantly smaller (50% and 64% decrease in VD and PE, respectively). The selective inhibitor of NO synthase, NG-nitro-L-arginine (L-NORAG) at 100 microM significantly attenuated the inflammatory response to BK in control rats (76% and 60% decrease in VD and PE, respectively) with a further decrease in the response in capsaicin pretreated rats. The inactive stereoisomer NG-nitro-D-arginine (D-NORAG) (100 microM) did not affect the inflammatory response to BK. The vasodilator response to SNP was intact in capsaicin pretreated rats and was not affected by either L-NORAG or D-NORAG.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1992

A memory clinic at a geriatric hospital: rationale, routine and results from the first 100 patients.

OBJECTIVE: To describe the operation of a memory clinic with reference to the referral pattern, patient characteristics and psychiatric diagnoses, frequency of reversible dementias and utility of brief cognitive screening tools in the detection of dementia. DESIGN: All patients underwent cognitive screening tests (Mini Mental Status Examination, Abbreviated Mental Test Score, Organic Brain Syndrome Scale of the Brief Assessment Scale) and two activities of daily living instruments. Psychiatric diagnoses were made according to criteria of the Diagnostic and statistical manual, third edition revised, of the American Psychiatric Association (DSM-III-R). SETTING: A large geriatric hospital. SUBJECTS: First 100 patients referred. RESULTS: The mean age of the patients was 75.5 years and 75 were women. Seventy-four met DSM-III-R criteria for dementia and a further 13 had other organic brain syndromes. No case of reversible dementia which recovered was encountered. The cognitive screening tools had a high correlation (r = 0.85-0.89) with one another but a much lower correlation with the activities of daily living instruments (r = 0.27-0.37). CONCLUSION: Reversible dementias are unlikely to be detected in a memory clinic at a geriatric hospital, but the assessment process may have other benefits which will need to be assessed in prospective research. The clinic population represents a unique resource for further research on dementia.

Activities of Daily Living↗

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↗