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Biomedical subjects

M K Nicholas

Publications and source records attributed to M K Nicholas.

16 recordsLinked to original sources

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

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

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

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

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

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

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

Comparison of T8+ cell-mediated suppressor and cytotoxic functions in multiple sclerosis.

Patients with progressive multiple sclerosis (MS) and controls were compared with regard to: (a) in vitro pokeweed mitogen (pwm)-induced IgG secretion, as an indirect measure of T8+ cell-mediated suppressor function; (b) alloantigen-directed cytotoxic activity, a predominantly T8+ cell-mediated function. The MS group had increased IgG secretion (4790 +/- 372 ng/ml vs. 1866 +/- 233 ng/ml, P less than 0.001) compared to controls. In contrast, alloantigen-directed cytotoxic activity did not differ between MS and control groups. These results suggest a selective defect of suppressor cell function in MS rather than a generalized dysfunction of T8+ cells. Defective immunoregulatory control coupled with preserved effector functions may contribute to the autoimmune process, suspected to underlie the pathogenesis of MS.

Adult

Suppressor and cytolytic cell function in multiple sclerosis. Effects of cyclosporine A and interleukin 2.

Patients with progressive multiple sclerosis (MS) demonstrated persistent reductions in levels of concanavalin A (Con A)-induced suppressor activity and heightened levels of in vitro pokeweed mitogen (PWM)-induced IgG secretion. The reduced Con A suppressor activity could not be reversed by addition of interleukin 2 (IL-2). Cyclosporine A (CsA) treatment did not alter the defect in Con A-induced suppressor activity, but did markedly inhibit T8+ cell-mediated alloantigen directed cytolytic activity; this latter defect was reversible by in vitro addition of IL-2. CsA-treated patients did not differ from placebo-treated patients with regard to levels of PWM-induced IgG secretion or proliferative responses of their mononuclear cells to Con A. The results indicate that CsA treatment of MS patients reduces cytolytic function from baseline normal values, but does not alter aberrant suppressor cell function.

Adult

Dissociation of T8+ cell-mediated cytolytic and suppressor functions in young adults.

In the normal young adult population, in vitro levels of polyclonally-induced IgG secretion by mononuclear cells (MNCs) vary widely amongst individuals. Levels of IgG secretion correlate with functional suppressor activity of T8+ cells but not with their proportion within the MNCs either prior to culture, or as found in this study, at the end of the culture period. The current study also demonstrates a lack of correlation between T8+ cell-mediated suppressor (Ts) function and a second predominantly T8+ cell-mediated function, alloantigen-directed cytolytic (Tc) activity. Whether this dissociation between Ts and Tc functions reflects quantitative differences in subsets contained within the T8+ population or qualitative differences in the mechanisms required for induction or generation of Ts and Tc remains to be established.

Adult

Passage of cows' milk protein in breast milk.

An enzyme-linked immunosorbent assay has been used to search for lactoglobulin and bovine casein in breast milk. Initial results suggest this may be a simple and useful method for such studies. Detection and prevention of antigen passage could influence the prevalence of atopic disease.

Animals

Characteristics, attitudes and personalities of AI donors.

The first 50 men recruited to an artificial insemination by donor (AID) programme have been assessed for their attitudes and characteristics using a basic questionnaire and a standard well evaluated personality inventory. The results have shown that donors can be characterized as stable and moderately extroverted people who come from a wide range of occupations. Their marital and parental status had no particular relationship to their desire to donate and most of them volunteered for altruistic reasons, financial remuneration being a poor inducement. Most subjects lived within the close environs of the Westmead Centre and preferred to donate during normal working hours. The inconvenience of donating appeared to be the most important factor in considering new approaches to recruiting semen donors.

Adult

Some attitudes to artificial insemination by donor.

A preliminary survey to assess and quantify attitudes to Artificial Insemination by Donor (AID) has been conducted with the aid of an article in a national magazine. The consensus of 375 individuals (mostly with a vested interest in infertility) concerning their attitudes to semen donation, hypothetical receipt of donor semen, legal aspects and the keeping of donor records, etc., have been analysed and their answers correlated to their age, sex, ethnic grouping, educational level, religion, and marital and fertility status as well as their place of residence. Within the limitations of this study, three major conclusions can be drawn. Firstly there are probably many potential semen donors in the general community and recruitment techniques need to be improved to capitalize on this source. Secondly, a centralized non-identifying National Register of donor information may be tolerated, and finally, the couples questioned felt an AID child should not be likened to one received through adoption. These and other findings would suggest that attitudes towards AID are changing and consequently some of the practices within AID programmes may need to be altered. Further statistically conducted surveys are warranted to determine these current attitudes.

Adult