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Biomedical subjects

I R Williams

Publications and source records attributed to I R Williams.

At least 19 recordsLinked to original sources
PubMed1992

Development of prognostic index for primary supratentorial intracerebral tumours.

The clinical course of intrinsic supratentorial tumours is variable. Prediction of outcome would be useful in defining patients for specific treatment policies. A retrospective analysis of 560 patients with intrinsic supratentorial tumours was performed. Proportional hazards models for survival were derived by using a stepwise selection procedure with only clinical and CT features as possible explanatory variables. The variables of prognostic importance were age, a first symptom of epilepsy, focal signs at presentation, a cystic lesion on CT scan, and duration of symptoms before presentation. The model defined a group with a good prognosis (score less than or equal to 9, n = 211) and a group with a poor prognosis (score greater than 9, n = 344). The median survival was 27 months for those with a score less than or equal to 9 or less and three months for those with score greater than 9. An alternative model, not including duration of symptoms, is also capable of defining groups with long (score less than or equal to 16, n = 234) and short (score greater than 16, n = 325) survival. The model may provide a means of classifying patients for inclusion in prospective randomised studies.

Actuarial Analysis↗
PubMed1992

Neurology in the market place.

The White Paper, "Working for Patients", led to a change in the way in which hospitals were funded from April 1991. The changes will have profound effects on the future shape of health care in the United Kingdom. Neurologists will need to understand the new National Health Service if their patients are to benefit from the changes. If neurology is to survive as a specialty separate from general medicine it will have to show that it can provide quality care which is accessible, relevant, efficient and effective, at a price which Districts can afford.

Contract Services↗
PubMed1991

Characterization of accessory cell costimulation of Th1 cytokine synthesis.

We studied the capacity of macrophage and B cell lines to provide a costimulatory signal that enhances synthesis of IFN-gamma and IL-2 by mouse Th1 clones stimulated with suboptimal doses of immobilized anti-CD3 antibody. The J774 macrophage line and the CH27 B lymphoma line had the greatest costimulatory activity and routinely increased IL-2 production by 10-fold to 100-fold. Other macrophage and B cell lines had less activity and T cell lines were unable to costimulate. The J774 and CH27 lines did not costimulate IL-4 production by a Th2 clone and had only a small effect on IL-2 production by T cell hybridomas. The process of costimulation was fixation-sensitive, contact-dependent and did not involve stable cytokines present in the T cell/accessory cell conditioned media. Neutralizing antibodies for IL-1, IL-6, and TNF failed to inhibit costimulation. Antibodies to the LFA-1/ICAM-1 pair of adhesion molecules also failed to inhibit. Costimulation of IL-2 production by accessory cells was found to have a unidirectional species restriction: mouse accessory cells costimulated mouse and human IL-2-producing T cells, but human U937 cells induced with PMA were effective only for human T cells. The results indicate that accessory cells can significantly regulate Th1 effector function at the level of cytokine production.

Animals↗
PubMed1991

The prognosis of primary intracerebral tumours presenting with epilepsy: the outcome of medical and surgical management.

It is not known whether conservative or early aggressive (resective surgery with or without radiotherapy) management is better for tumours presenting with epilepsy. The prognosis of 560 patients with a clinical and CT diagnosis of intrinsic supratentorial tumour was examined retrospectively. Epilepsy was the first symptom in 164 patients. Histological confirmation of diagnosis was available in 391 (70%) of cases. Median survival was 37 months in the group presenting with epilepsy and six months in those presenting with other symptoms (p less than 0.0001). Patients presenting with epilepsy were more likely to have a normal clinical examination, a non-enhancing low density lesion on CT scan and a low grade tumour. From Cox's stepwise proportional hazards model, significant independent variables adversely affecting prognosis were increasing age, focal neurological signs and enhancing CT lesions at diagnosis, non-resective surgery and male sex. Of those presenting with epilepsy 80 patients had surgical treatment within two months of CT diagnosis. The Cox's model failed to identify any beneficial effects for either early resective surgery or radiotherapy. In primary intracerebral tumours with presentations other than epilepsy, resective surgery and radiotherapy were amongst the important factors associated with prolonged survival. Primary intracerebral tumours presenting with epilepsy are relatively benign and their outcome appears to be chiefly determined by clinical factors.

Adolescent↗
PubMed1991

Unrecognised Cushing's syndrome and adrenal suppression due to topical clobetasol propionate.

A 53-year-old man with cushingoid appearance--obesity, osteoporosis causing lumbar and thoracic vertebral collapse and a past history of hypertension and depression presented with symptoms and signs of adrenocortical insufficiency. He denied the use of corticosteroid medication. However, it was eventually discovered that he had used clobetasol propionate (Dermovate), a potent topical steroid cream, for five years. The development of adrenal insufficiency symptoms coincided with the withdrawal of the cream.

Adrenal Insufficiency↗
PubMed1990

Costimulatory requirements of murine Th1 clones. The role of accessory cell-derived signals in responses to anti-CD3 antibody.

We examined the role of accessory cell-derived signals in promoting growth and lymphokine production by murine Th1 clones. Five of six Th1 clones failed to proliferate to immobilized anti-CD3 antibody despite producing IL-2 and IFN-gamma. These clones became unresponsive to Ag after exposure to anti-CD3. With the addition of irradiated splenic accessory cells (SAC), Th1 clones proliferated to anti-CD3 and produced greater amounts of IL-2 and IFN-gamma. High doses of plate-bound anti-CD3 completely inhibited responses of these clones to IL-2 and diminished the growth-promoting activity of SAC. The costimulatory effects of SAC on growth of Th1 clones were also seen in the presence of exogenous IL-2, indicating that enhanced IL-2 production alone was not responsible for the costimulatory effect. Delivery of the costimulatory signal from SAC required their close proximity to the T cells. The costimulatory activity of SAC was not reproduced by the addition of IL-1, IL-6, or IL-1 plus IL-6. IL-7 induced weak proliferation of Th1 clones, but did not synergize with plate-bound anti-CD3. Our results suggest a model in which SAC-derived costimulatory signals regulate growth of Th1 cells primarily at the level of cell cycle progression rather than at the level of IL-2 production.

Animals↗
PubMed1990

The management of patients with an intrinsic supratentorial brain tumour.

The management of patients presenting with supratentorial glioma between 1978 and 1986 is reviewed. Complete follow-up in 517 cases was obtained. One hundred and fifty eight patients were not submitted to any form of surgery, 299 patients were biopsied and 60 patients underwent craniotomy and internal decompression. The no surgery group contained a higher proportion of patients with poor prognostic indicators than either the biopsy or craniotomy groups. The craniotomy group consisted of patients with better prognostic indicators than the biopsy group, in particular, younger age and more favourable site, type and grade of tumour. This was reflected in the difference in outcome between the groups. Median survival was 14 months in the craniotomy group, four months in the biopsy group and 2.2 months in the no surgery group. The outcome in patients with histologically proven malignant gliomas was best in those patients who received radiotherapy. The craniotomy group had a median survival of 18.5 months, a two year survival of 48% and a five year survival of 9%. The median survival following radiotherapy of those patients with proven malignant gliomas who had a biopsy was 9.5 months with a two year survival of 16% and a five year survival of 2%. These results compare favourably with studies which have adopted a more aggressive approach, suggesting that outcome is determined as much by patient selection using favourable prognostic indicators as by the treatment itself. The need for prospective trials of the management of unselected consecutive glioma patients randomizing them to conservative and radical treatment groups in order to define the role of both conventional therapy and radical therapy is discussed.

Adolescent↗
PubMed1986

Differences between neurological and neurosurgical approaches in the management of malignant brain tumours.

The management and outcome in 205 patients diagnosed as having cerebral gliomas over five years were reviewed. Patients referred to neurologists and neurosurgeons had similar clinical features and similar results on computed tomography. Patients referred to neurologists underwent burr hole biopsy less often and had better short term morbidity than patients referred to neurosurgeons, although final outcome was the same in both groups. Few patients underwent other surgical procedures. Referral for radiotherapy was usually by neurosurgeons, although this did not significantly affect long term survival. The implications for the management of patients with primary malignant brain tumours and the need for prospective studies are discussed.

Adolescent↗
PubMed1985

A double determinant sandwich immunoassay for quantitation of serum monoclonal anti-I-A antibody.

A double-determinant sandwich radioimmunoassay (RIA) is described for the specific detection of anti-I-Ak monoclonal antibody (mAb) in the sera of non-Ighb murine hosts undergoing anti-Ia immunotherapy. This RIA utilizes 2 previously undescribed mAb reagents generated against an Ia.17-specific mAb secreted by the 10-3.6 hybridoma. The first reagent, 7.34, is specific for Ighb-linked allotypic determinants on the Fc portion of IgG2a immunoglobulins as defined by the pattern of reactivity with normal sera from a panel of inbred and Igh recombinant inbred strains. The second reagent, 58.3, is an anti-idiotypic mAb recognizing unique determinants in the combining site of 10-3.6 immunoglobulins, as determined by the specificity of the 58.3 mAb in solid-phase RIA and the capacity of this reagent to inhibit the binding of labeled 10-3.6 mAb to I-Ak-expressing spleen cells. In an RIA procedure using purified 58.3 mAb as substrate and 125I-labeled 7.34 as the detection reagent, serum concentrations of 10-3.6 as low as 1-5 ng/ml can be measured reproducibly after mathematical linearization of the sigmoid standard curve. In the present studies, the serum half-life of 10-3.6 mAb was calculated from assay data to be 3-5 h in I-Ak homo- or heterozygotes and 72 h in non-I-Ak mice. The serum level of 10-3.6 as a function of the mAb treatment protocol was also examined and results are considered with respect to the efficacy of different therapeutic regimens in prolonging transplant survival. Sandwich immunoassays of this type (RIA or ELISA) should provide a highly sensitive and specific means for monitoring serum mAb levels in individuals subjected to antibody immunotherapy for treatment of autoimmune disease, transplant rejection or tumor progression.

Animals↗
PubMed1985

Regulation of transplantation immunity in vivo by monoclonal antibodies recognizing host class II restriction elements. I. Genetics and specificity of anti-Ia immunotherapy in murine skin allograft recipients.

Antibodies reactive with host class II restriction elements exert profound regulatory effects on the immune response to a variety of antigenic stimuli, including tumor, autoantigens, and alloantigens. In the present studies, monoclonal reagents specific for host I-A and I-E glycoproteins were evaluated for their capacity to modulate transplantation immunity in a murine tail skin allograft system. It was found that treatment of A/J mice with 200 micrograms 10-3.6 hybridoma-derived anti-I-Ak antibody daily for 10 days resulted in an average twofold increase in the survival time of B10.A minor antigen-incompatible allografts. Similar results were achieved by using class I, but not H-2-mismatched, donor tissue. Specificity of antibody activity was demonstrated by the failure of isotype-matched reagents recognizing irrelevant class II or relevant class I H-2 antigens to influence rejection under these conditions. Although antibodies reactive with graft as well as host alloantigens provided the greatest degree of prolongation, interaction with host restriction elements alone was sufficient for the in vivo expression of regulatory activity. As in previous studies, anti-I-A treatment was associated with the development of antigen-specific suppressor T cells that serve to dampen allograft immunity without altering secondary responses to unrelated antigens encountered after the initial treatment interval. These data suggest that anti-Ia immunotherapy may provide a clinically relevant approach toward the specific regulation of transplantation immunity in the appropriate donor-recipient combinations.

Animals↗
PubMed1985

Regulation of transplantation immunity in vivo by monoclonal antibodies recognizing host class II restriction elements. II. Effects of anti-Ia immunotherapy on host T cell responses to graft alloantigens.

Results of the preceding report demonstrated that in vivo treatment with monoclonal anti-I-A antibodies provided an effective means of prolonging the survival of murine tail skin allografts. The mechanism of antibody action was shown to include the activation of alloantigen-specific suppressor T cells (Ts), although the relationship between Ts expression and graft survival was not determined. This issue was addressed in the current studies through a kinetic analysis of suppressor and effector T cell responses in control and treated allograft recipients. Donor-specific delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) responses were detectable in untreated A/J recipients of B10.A allografts 8 days after transplantation, rising to near maximum levels by day 12. Rejection in these animals occurred by day 11. In contrast, the predominant cellular response of anti-I-A treated animals for 12 days after transplantation was that of transferable suppression, DTH and CTL reactivity not being evident until day 15, coincident with the decay of Ts activity. Rejection in these animals was observed approximately 19 days post-transplant. CTL responsiveness in the latter group could not be reconstituted by the addition of antigen-presenting cells to the secondary in vitro culture system, nor was the CTL deficit due to antibody carry-over. It is considered that the altered expression of effector cell responses to graft alloantigens is due at least in part to the in vivo inhibition of helper T cell activity by anti-I-A-induced Ts, and that rejection in the treated host results from an eventual decline in the functional expression of this regulatory T cell subset.

Animals↗
PubMed1978

Peripheral nerve conduction in patients with a cervical rib and band.

In 14 patients with wasting of the hand due to a cervical rib and band, motor and sensory conduction studies on the peripheral parts of the median and ulnar nerves were helpful in establishing the correct diagnosis. The median nerve findings excluded carpal tunnel syndrome even when the clinical pattern of wasting in the hand suggested this diagnosis. Preservation of conduction velocity in the ulnar nerve excluded ulnar entrapment at the elbow; the reduced amplitude of the ulnar sensory action potentials (SAPs) indicated that the lesion was distal to the dorsal root ganglia. In 3 patients with ulnar SAP amplitudes that were low but not clearly abnormal, the level of the lesion was confirmed by a reduced response to intradermal injection of histamine on the inner side of the forearm.

Action Potentials↗
PubMed1978

Extrajunctional acetylcholine sensitivity of inactive muscle fibres in the baboon during prolonged nerve pressure block.

1. Nerve-evoked muscular activity was abolished in the small hand muscles of the baboon for 1-2 months by a 3 hr period of nerve compression from a pneumatic tourniquet inflated round the forearm. In the large diameter nerve fibres, this produced either a prolonged conduction block due to local myelin damage at the site of compression, or (in 10-30% of the large fibres) Wallerian degeneration. 2. At varying intervals after nerve compression the extrajunctional acetylcholine (ACh)-sensitivity of innervated but inactive muscle fibres in the fourth lumbrical muscle was measured. Observations were also made on lumbrical muscle fibres at similar intervals after surgical denervation. 3. The ACh sensitivity of nerve-blocked muscle fibres started to develop later than in denervated muscle fibres (10 vs. 7 days) and remained at a lower level (40-80 mV/nC, median ACh-sensitivity) than that of denervated muscle fibres (200-437 mV/nC) from 21 to 63 days after nerve block or denervation. 4. In stimulation experiments on four muscles, extrajunctional ACh-sensitivity of both denervated and innervated but inactive fourth lumbrical muscle fibres was reduced by muscular activity. 5. In four animals mild compression was used in the lower limb to produce persistent nerve block without Wallerian degeneration. With one exception (in which some Wallerian degeneration had occurred) recording with a co-axial needle from abductor hallucis showed no spontaneous fibrillation up to 28 days after compression, although the extrajunctional ACh-sensitivity of the muscle fibres appeared to reach levels similar to those observed in the forelimb. All four muscles developed a slight increase in insertion activity after 1-2 weeks. 6. It may be concluded that both muscular activity and some other neural influence, independent of muscular activity, are able to influence extrajunctional muscle properties in the baboon. The neural influence appears to be more effective in preventing spontaneous fibrillation than in preventing a rise in ACh sensitivity of the extrajunctional muscle membrane.

Acetylcholine↗
PubMed1977

Regeneration distal to a prolonged conduction block.

In 6 baboons a tourniquet round the knee was used to produce a prolonged local conduction block. This was followed, within a few days, by a surgical crush of the tibial or deep peroneal nerve at the ankle, in order to produce Wallerian degeneration distally. Electrophysiological recordings from small foot muscles were then used to study the time-course of regeneration in motor fibres. When the results were compared with those from crushed but unblocked nerves of the opposite leg, there was no evidence that either reinnervation of muscles or the subsequent maturation of the regenerating motor nerve fibres was delayed by the prolonged proximal conduction block.

Animals↗