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Biomedical subjects

M K Nicholas

Publications and source records attributed to M K Nicholas.

At least 19 recordsLinked to original sources
PubMed2004

Modification of attentional biases in chronic pain patients: a preliminary study.

Research suggests that chronic pain patients demonstrate cognitive biases towards pain-related information and that such biases predict patient functioning. This study examined the degree to which a successful cognitive-behavioural program was able to reduce the observed attentional bias towards sensory pain words. Forty-two patients with chronic pain conditions for more than three months were recruited prior to commencing a cognitive-behavioural pain management program. Participants were assessed before the program, after the program and at one-month follow-up. Results confirmed that chronic pain patients exhibited biased attention towards sensory pain-related words at pre-treatment. These biases were still evident at post-treatment, but were no longer statistically significant at follow-up. Multiple regression analyses indicated that the changes in attentional bias towards sensory words between post-treatment and follow-up were predicted by pre- to post-treatment changes in fear of movement (Tampa Scale for Kinesiophobia) but not other relevant variables, such fear of pain or anxiety sensitivity. These results demonstrate that successful cognitive-behavioural treatments can reduce selective attention, thought to be indicative of hypervigilance towards pain. Moreover, these biases appear to be changed by reducing the fear associated with movement. Theoretically, these results provide support for the fear of (re)injury model of pain. Clinically, this study supports the contention that fear of (re)injury and movement is an appropriate target of pain management and that reducing these fears causes patients to attend less to pain-related stimuli.

Adult↗
PubMed2003

Pain differs from non-painful attention-demanding or stressful tasks in its effect on postural control patterns of trunk muscles.

Pain changes postural activation of the trunk muscles. The cause of these changes is not known but one possibility relates to the information processing requirements and the stressful nature of pain. This study investigated this possibility by evaluating electromyographic activity (EMG) of the deep and superficial trunk muscles associated with voluntary rapid arm movement. Data were collected from control trials, trials during low back pain (LBP) elicited by injection of hypertonic saline into the back muscles, trials during a non-painful attention-demanding task, and during the same task that was also stressful. Pain did not change the reaction time (RT) of the movement, had variable effects on RT of the superficial trunk muscles, but consistently increased RT of the deepest abdominal muscle. The effect of the attention-demanding task was opposite: increased RT of the movement and the superficial trunk muscles but no effect on RT of the deep trunk muscles. Thus, activation of the deep trunk muscles occurred earlier relative to the movement. When the attention-demanding task was made stressful, the RT of the movement and superficial trunk muscles was unchanged but the RT of the deep trunk muscles was increased. Thus, the temporal relationship between deep trunk muscle activation and arm movement was restored. This means that although postural activation of the deep trunk muscles is not affected when central nervous system resources are limited, it is delayed when the individual is also under stress. However, a non-painful attention-demanding task does not replicate the effect of pain on postural control of the trunk muscles even when the task is stressful.

Abdominal Muscles↗
PubMed2000

Assessing the significant others of chronic pain patients: the psychometric properties of significant other questionnaires.

Contemporary reviews of psychological models of chronic pain have favoured behavioural and cognitive-behavioural formulations. These have often assumed that pain behaviours are maintained by environmental reinforcers. One of the most commonly hypothesized sources of reinforcement has been patients' significant others. Further, it has often been recognized that significant others may also be affected by pain behaviours and that they may experience changes in their lifesyles and in their mood as a consequence of living with someone who has pain. Somewhat surprisingly, relatively little clinical research has been published investigating significant others and their relationships with pain patients. Among other things, one of the limiting factors has been the lack of measurement tools available for assessing the relevant variables thought to be important with regards to significant others (such as their responses to, and perceptions of, chronic pain). This study attempted to remedy this situation by developing and testing the psychometric properties of a number of questionnaires specifically designed for significant others of chronic pain patients. The questionnaires have been selected to assess both significant others' (behavioural and cognitive) responses to pain as well as the extent to which pain impacts on their lives. Although not all of the questionnaires were found to possess equally strong psychometric properties, the availability of several solid measures opens the way for more empirical analyses of significant others and their interactions with chronic pain patients.

Adaptation, Psychological↗
PubMed1999

Generalizing from a controlled trial: the effects of patient preference versus randomization on the outcome of inpatient versus outpatient chronic pain management.

Patients accepting randomization in a randomized controlled trial (RCT) may not be representative of the clinical population from which they are drawn, calling into question the generalizability of study findings. Comparison of randomized and non-randomized inpatient and outpatient samples at baseline and in treatment outcomes up to one year was made to determine whether the findings of the RCT generalized to non-randomized patients in the same treatment program. One hundred and twenty one patients with intractable pain, randomized between inpatient, outpatient and waiting list control, were compared with 128 who elected for either inpatient or outpatient treatment. Treatment was a group-based multidisciplinary cognitive-behavioral treatment program aimed at enabling patients to return to more normal function despite persistent pain, delivered to mixed groups of randomized and elective patients, and outcome was measured by physical performance, pain impact on function, mood, and drug use. Agreement to randomization was a function of travelling distance from home to hospital. Non-randomized patients largely resembled their randomized counterparts before and after treatment. In order to indicate the clinical significance of results, analyses were conducted using numbers needed to treat (NNTs). NNTs estimate the number of patients required in the treatment condition for one of them to achieve the specified outcome who would not have achieved it in the comparison condition. Across a range of measures at one month follow-up, comparison of inpatients with outpatients gave NNTs between 2.3 and 7.5, and comparison of inpatients with waiting list controls gave NNTs between 2.3 and 3.6. At one year inpatients showed greater likelihood than outpatients of maintaining these treatment gains.

Adult↗
PubMed1999

Pharmacokinetics and pharmacodynamics of 9-aminocamptothecin infused over 72 hours in phase II studies.

A novel derivative of camptothecin, 9-aminocamptothecin (9-AC), is currently under Phase II evaluation in various cancers. Exceptionally mild toxicities were observed in patients with brain tumors who were treated with anticonvulsants. To investigate a pharmacokinetic interaction between 9-AC and anticonvulsants, and to evaluate the pharmacodynamics of 9-AC, we investigated the clinical pharmacology of 9-AC, administered by a 72-h infusion, in three Phase II studies. Plasma concentrations of total 9-AC (lactone plus carboxylate) at a steady state were measured in 56, 10, and 14 patients with non-small cell lung cancer, malignant glioma, and head and neck cancer, respectively. For lung cancer or glioma patients, 9-AC was infused at 45 (51 patients) or 59 (15 patients) microg/m2/h, and 9-AC was infused at 35.4 microg/m2/h in head and neck cancer patients. All glioma patients had been treated with phenytoin or carbamazepine. 9-AC clearance did not differ among the dosage rates, but differed according to the diseases (P = 0.002). Glioma patients had a higher clearance (1.0-18.0; median, 2.0 liters/h/m2) than lung cancer patients (0.3-5.1; median, 0.9 liters/h/m2). A logistic regression model described the relationship between the 9-AC concentration and the probability of grade 4 neutropenia, which was the main toxicity. Observed incidences of grade 4 neutropenia for patients with model-predicted probability of 0-20%, 20-40%, and 40-100% were 10%, 32%, and 67%, respectively, and corresponded to 9-AC concentration of <54, 54-86, and >86 ng/ml, respectively. Anticonvulsants seem to induce the clearance of 9-AC, and the concentration of 9-AC predicts the probability of grade 4 neutropenia.

Adult↗
PubMed1998

High dose oral tamoxifen and subcutaneous interferon alpha-2a for recurrent glioma.

Chemotherapeutic regimens in present use for recurrent glioma have substantial toxicity. Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy. Interferon-alpha [6 x 10(6) U subcutaneously three times per week] and tamoxifen (240 mg/m2/day orally) were administered continuously. Treatment response was assessed at 6 week intervals using clinical and radiographic criteria. Eighteen patients (11 males and 7 females) were enrolled. Median age was 41 years (range 23-61 years). All patients had gliomas that progressed after radiation therapy and nitrosourea chemotherapy. The histologic diagnosis of the original tumor was glioblastoma multiforme in 8 patients, anaplastic astrocytoma in 5 patients, astrocytoma in 4 patients and mixed malignant glioma in 1 patient. Reversible moderate to severe neurological toxicity manifested by dizziness and unsteady gait was seen at tamoxifen doses of 240 mg/m2/day. Although the initial tamoxifen dose was reduced to 120 mg/m2/day, moderate neurotoxicity was noted at this dose as well and the trial was closed early. The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure. Of 16 evaluable patients, 12 had progressive disease after one cycle of treatment, 3 had stable disease, and there was one minor response. Gradual dose escalation may be required if similar patients are to be treated with high dose tamoxifen in conjunction with interferon.

Administration, Oral↗
PubMed1997

An investigation of the placebo effect and age-related factors in the report of needle pain from venipuncture in children.

To examine the potential role for a placebo cream in reducing reported needle pain severity in children, and the impact of age-related factors on pain self-report, a convenience sample of 117 children scheduled for venipuncture were randomly assigned to one of three treatments: (a) placebo cream with the suggestion that it might help reduce needle pain, (b) placebo cream with no indication as to the cream's purpose, and (c) no cream (control group). In allocation to treatment, children were stratified by age group, (3-7, 8-11, 12-17 years). They rated their needle pain severity (both predicted and reported) using the Faces Pain Scale, and rated their anxiety about the procedure using the Children's Anxiety and Pain Scale. Children in the cream groups were also asked whether they thought the cream had helped. Using video-tapes, an independent observer, blind to the placebo manipulation, rated each child's reaction to the needle. For the two groups receiving cream, 83% of those children told it might help stated that they believed it did, as compared with only 33% of children who received the cream but were told nothing of its purpose. These beliefs, however, were not reflected in self-report ratings of pain which showed no statistically significant treatment effect. Similarly, children who gave higher preprocedural anxiety ratings were no more likely to report less pain as a result of receiving the cream. There was, however, a treatment effect on the observer's ratings: children receiving cream plus suggestion were assigned significantly lower ratings of pain-related behaviour than those children who received the cream alone. While venipuncture was associated with only mild levels of pain, younger children, irrespective of treatment group, did report more pain than older children. Hierarchical regression analysis indicated that 60% of the variance in self-reported pain severity scores could be accounted for by how much the child thought the needle would hurt, how anxious the child was about receiving the needle, gender (higher pain ratings associated with girls), and estimated body surface area (higher pain ratings associated with smaller bodies). We conclude that the efficacy of placebo treatments for needle pain in children may depend on the suggestion of a possible benefit rather than upon treatment application per se.

Adolescent↗
PubMed1996

Inpatient vs. outpatient pain management: results of a randomised controlled trial.

Inpatient and outpatient cognitive behavioural pain management programmes for mixed chronic pain patients were compared. Patients were randomly allocated to the 4 week inpatient programme or to the 8 half day per week outpatient programme, or to a waiting list control group. Staff, teaching materials, and setting were the same for the two treatment groups. Patients were assessed pre-treatment, and at 1 month after discharge, and treated patients also at 6 months and 1 year after discharge, by assessors blind to treatment group; assessments included physical, functional and psychological measures, and medication use. In total, 121 mixed chronic pain patients (mean age 50 years; mean chronicity 8.1 years) were included in the study, following medical examination to ensure that no further medical treatment was appropriate. There was no change in the control group; inpatients and outpatients, comparable before treatment, both made significant improvements in physical performance and psychological function, and reduced medication use. Inpatients made greater gains, and maintained them better at 1 year; they also used less health care than outpatients. There were no outstanding predictors of improvement other than treatment group.

Ambulatory Care↗
PubMed1993

Evaluation of a cognitive behavioural programme for rehabilitating patients with chronic pain.

The aim of this prospective longitudinal study was to evaluate an inpatient cognitive behavioural pain management programme for patients with chronic pain. A physical and psychological assessment of patients was carried out before and after treatment, and at one and six months follow up. A total of 212 patients with disabling chronic pain of mean duration 10.5 years, for whom no further medical or psychiatric treatment was appropriate or available, were admitted; their mean age was 50 years and 65% were women. The four week programme was delivered by a multidisciplinary team of two psychologists, a physiotherapist, nurse, occupational therapist and anaesthetist. The main components of therapy included: education, teaching behavioural and cognitive skills, a stretch and exercise programme, medication reduction, goal setting and pacing, and relaxation training. Outcome measures assessed quality of life, physical performance (for example walking speed), pain intensity and distress, depression severity and confidence. Assessment immediately after treatment revealed significant improvements on all measures. Improvements were well maintained at six month follow up. Cognitive behavioural treatment can be of value in improving the day-to-day functioning and quality of life of patients with chronic pain for whom conventional medical treatments have apparently failed.

Adult↗
PubMed1991

Operant-behavioural and cognitive-behavioural treatment for chronic low back pain.

Fifty-eight outpatients with chronic low back pain were randomly allocated to one of six experimental conditions. Four conditions were designated as treatment conditions and two as control conditions. The four treatment groups consisted of: cognitive treatment (either with or without relaxation training) and behavioural treatment (either with or without relaxation training). The cognitive and behavioural groups also received physiotherapy. The two control conditions consisted of: attention (physiotherapy plus discussion sessions) and no-attention (physiotherapy-only) conditions. All conditions, including the two controls, received the same physiotherapy back-education and exercise program. For the sample as a whole, improvements were obtained on measures of affective distress, functional impairment, medication use, pain-related dysfunctional cognitions and use of active coping strategies. These improvements were generally maintained at 6- and 12-month follow-ups. The combined psychological/physiotherapy treatment conditions improved significantly more than the physiotherapy-only conditions from pre to posttreatment on measures of pain intensity, self-rated functional impairment and pain-related dysfunctional cognitions. However, these differences were only weakly maintained at 6- and 12-month follow-ups. The behavioural conditions improved significantly more than the cognitive conditions from pre to posttreatment on the self-rated measure of functional impairment, but this difference was not maintained at 6- and 12-month follow-ups. Progressive relaxation training was found to make little contribution to either cognitive or behavioural treatments.

Adult↗
PubMed1991

Psychological approaches in chronic pain management.

Psychological factors are contributory to the genesis and maintenance of many chronic pain syndromes. Treatment can be delivered either as one component of multimodal therapy or as the sole approach in a pain management programme. This distinction is important as it has a bearing on the goals of treatment, which in the latter situation is to improve management of the pain and encourage the patient to take more responsibility for their treatment, rather than cure the illness. Treatment typically comprises elements of operant conditioning, where activity and performance can be substantially improved, and cognitive therapy where the thoughts and emotions associated with the pain are tackled, leading to diminution of distress. Relaxation training is also of benefit. The documented success of these techniques in various settings suggests that psychological treatment should be considered a necessary component of any multidisciplinary clinic offering therapies to chronic pain sufferers.

Behavior Therapy↗
PubMed1988

Activated suppressor cell function in multiple sclerosis--clinical correlations.

Activated suppressor cell function mediated by either freshly isolated peripheral blood mononuclear cells (MNCs), freshly isolated CD8+ lymphocytes or by CD8+ cell lines, has previously been found to be reduced compared to controls in multiple sclerosis (MS) patients with progressive disease (MS-P). In this study, we found that suppressor activity mediated by CD8+ cell lines, derived from MS patients with stable disease (MS-S) patients and maintained in culture for 14 days, was significantly greater (45 +/- 6%) compared to that mediated by MS-P patients' CD8+ cells (11 +/- 4%, P less than 0.005). The MS-S suppressor values were, however, suggestively reduced compared to controls (60 +/- 6%, P less than 0.05). MNC-mediated suppressor values for the MS-S group (61 +/- 5%) did not differ from the control group (67 +/- 6%). Values for the MS-P group (7 +/- 6%) were significantly reduced compared to MS-S and control groups. Cytotoxic activity mediated by CD8+ cell lines showing defective suppressor function did not differ from control values. The cell lines in MS and control did not differ with respect to their rate of proliferation in the presence of IL-2 and OKT3. Suppressor function in this assay was ablated if exogenous IL-2 was removed from the culture media. These data suggest that defective activated suppressor function is characteristic of the progressive form of MS, although a suppressor defect is also partially expressed in stable MS patients when CD8+ cell lines are studied.

Adult↗
PubMed1987

Rejection of fetal neocortical neural transplants by H-2 incompatible mice.

In order to examine questions concerning immunologic privilege of the central nervous system, we placed neocortical transplants into cerebral ventricles of mice. We compared the fates of transplants between fully H-2 compatible (isografts) and H-2 incompatible (allografts) animals. Histologic evaluation comparing animals from iso- and allograft groups revealed significant differences in the number of inflammatory cells and in the degree of necrosis within the grafts. Response to allografted tissue within the brain mimics that seen in several immune-mediated diseases of the nervous system in that neurons appear to be selectively spared. Only upon subsequent stimulation of the host's immune system with an orthotopic skin graft bearing the major histocompatibility complex antigens of the neural graft are neurons destroyed. Immunohistochemical evaluation revealed that the inflammatory cell infiltrates in and around the allografts were composed of Lyt-2+, L3T4+, and Mac-1+ cells. In addition, Ia+ endothelial cells as well as Ia+ parenchymal CNS cells were found in both donor and host tissue of allografted animals. Hence, H-2 incompatible neural tissue transplanted to the CNS is recognized and rejected by the immune system of the recipient animal. The cellular infiltrates seen within the first weeks to months following transplantation of allogeneic CNS tissue resemble those seen in other allografts undergoing rejection. We conclude that the CNS is not unconditionally privileged as either a transplant site or as a source of transplanted tissue.

Animals↗
PubMed1987

An in vivo and in vitro analysis of systemic immune function in mice with histologic evidence of neural transplant rejection.

Histologic and immunocytochemical analyses of fetal neocortical tissue transplanted to the lateral ventricle of inbred adult mice indicate that this tissue survives transplantation well if the donor and host are isogeneic. The major histocompatibility complex (MHC) of the mouse is known as the H-2 locus. H-2-incompatible neural transplants (allografts), unlike their H-2-identical counterpart (isografts), are characterized by the presence of T cells comprising both major T-cell subsets and macrophages, and by a marked increase in the expression of both class I and class II (Ia) MHC antigens. These findings suggest a recognition of H-2 alloantigens by the host's immune system followed by an appropriate effector response. We report here our attempts to demonstrate systemic host sensitization to alloantigens in mice bearing H-2-incompatible intraventricular neural transplants. We measured the time to rejection of orthotopic skin grafts subsequent to neural transplantation, splenocyte proliferative responses to alloantigens in mixed lymphocyte cultures (MLC), and class I-restricted antigen-specific cytolytic T lymphocyte (CTL) activity. No significant differences were found in any of these tests of host systemic sensitization between mice with allogeneic neural transplants and those with isogeneic transplants or control animals. We conclude that intraventricular neural transplants, while recognized and affected by cells of the host's immune system, do not elicit a detectable systemic sensitization to class I H-2 alloantigens. Rejection of neural transplants may depend on sensitization to class II H-2 alloantigens, to so-called minor histocompatibility antigens, or some combination thereof.

Animals↗