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Biomedical subjects

I R Williams

Publications and source records attributed to I R Williams.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1984

Suppressor T cell recognition of major and minor histocompatibility alloantigens: selected suppression of MHC-directed responses by minor alloantigen Ts.

The induction of suppression by i.v. administered alloantigens in the murine host was analyzed as a model of the possible effects of blood transfusion on transplant survival. The results indicated that suppressor T cells (Ts) specific for minor histocompatibility alloantigens could be readily induced by the i.v. presentation of minor alloantigen-disparate spleen cells. In contrast, similar priming with cells differing solely at the H-2 major histocompatibility complex stimulated only positive T cell immunity, with no evidence of suppression. The induction of H-2 directed Ts activity could be accomplished only by i.v. priming with major plus minor incompatible donor cells, suggesting that suppressor cell recognition of minor alloantigens may have facilitated the generation of Ts against H-2-encoded major transplantation antigens. A role for minor histocompatibility antigens in the regulation of H-2-specific immunity at the effector level was also indicated. Ts induced by i.v. pretreatment with minor antigen-disparate donor cells not only suppressed the delayed-type hypersensitivity (DTH) response to the relevant minor alloantigens, but also inhibited DTH against unrelated H-2 alloantigens introduced during subsequent intradermal immunization. Suppression of H-2-directed T cell reactivity was specific in that the presence of the Ts-inducing minor alloantigens was also required and occurred only when the minor and unrelated major alloantigens were presented within the same inoculum, if not on the same cell surface. The capacity of Lyt-2+Ts or Ts-derived suppressive factors specific for one set of cell surface molecules to modulate responses to an unrelated group of surface antigens does not appear to represent a general phenomenon, because similar suppression of immunity to unrelated tumor-specific transplantation antigens by minor-specific Ts was not observed. These results are discussed with respect to the possible mechanism of H-2-directed suppression and the role of the I region in Ts recognition of antigen.

Animals↗
PubMed1981

The effect of afferent stimuli on steadily discharging single motor units in man.

The effect of afferent stimuli on the firing pattern of single motor units has been studied in the human first dorsal interosseous muscle of the hand. A reproducible series of changes in the probability of motor unit firing was seen. There was evidence for an excitatory spinal reflex involving median nerve muscle afferent fibres and ulnar nerve motor fibres. Cutaneous and muscle afferent pathways expected to be important in the control of fine movement of the first digit produced an excitatory reflex response at about 70 ms. All sites stimulated in the ipsilateral limb gave rise to a profound reduction in motor unit firing from about 70-130 ms.

Adult↗
PubMed1981

The role of vertebral angiography in the investigation of third nerve palsy.

The association between intracranial aneurysm and third nerve palsy in a series of fifty patients presenting to this unit over a six year period has been studied. All aneurysms causing a third nerve palsy were found to be in the anterior circulation and all were adequately demonstrated by carotid angiography alone. None of the thirty cases of posterior circulation aneurysm was associated with a third nerve palsy. Vertebral angiography carries a higher risk of serious complications than carotid angiography. We feel that the added risk of vertebral angiography is not justified for the investigation of an isolated third nerve palsy.

Carotid Artery, Internal↗
PubMed1980

Acute nerve compression during limb ischaemia--an experimental study.

In 6 baboons the deep peroneal nerve was compressed for 1 hr by a weighted cord laid over the leg just above the ankle. The procedure was carried out on both sides in a single experiment. On one side the whole leg was rendered ischaemic by a cuff round the thigh which was maintained for 3 or 4 hr before and during the period of nerve compression at the ankle. As judged by the severity of the conduction block at the ankle 24 hr later, and its subsequent recovery, the compressed nerves which were also made ischaemic fared no worse than those subjected to compression alone. Histological studies showed evidence of selective damage to large myelinated fibres during the compression; this damage was not increased on the ischaemic side. There is thus no evidence that ischaemia increased the susceptibility of nerve fibres to mechanical damage in these experiments.

Acute Disease↗
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↗
PubMed1976

Peripheral motor nerve function in diabetic autonomic neuropathy.

Motor conduction velocity was measured in the median, ulnar and common peroneal nerves of 32 diabetics with clinical features of autonomic neuropathy. The responses to the Valsalva manoeuvre and sustained handgrip, and the postural fall in blood pressure were used to assess the integrity of the autonomic nervous system. Abnormalities in the three autonomic function tests were significantly correlated with the forearm conduction velocity of the ulnar nerve, the conduction velocity and motor latency of the common peroneal nerve, and the H reflex. These results show that, in diabetics with autonomic neuropathy, abnormalities in the autonomic nervous system parallel changes in the peripheral nerves. Any diabetic with peripheral neuropathy should be examined for evidence of autonomic nervous system involvement.

Adult↗
PubMed1976

Subacute proximal diabetic neuropathy.

The results of clinical, electrophysiologic, and histologic studies in three patients with a type of diabetic peripheral neuropathy, subacute proximal diabetic neuropathy (diabetic amyotrophy), are presented. On the basis of our findings, we suggest that diabetic amyotrophy is a clinical and pathologic entity separate from mononeuritis multiplex. These patients have a generalized neuropathy, and it is postulated that disordered neuron-axonal metabolism forms the basis for the pathologic and clinical changes. Histochemical changes in the muscle biopsy showed type 1 predominance. We suggest that this phenomenon represents a conversion of surviving fibers of whatever type, to a type 1 oxidative metabolism because of the change in use of these fibers.

Aged↗