Hyperimmune goat serum (Aimspro): hope or hype?
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Animals↗
Biomedical subjects
Ian Sutton
Publications and source records attributed to Ian Sutton.
The pathology of multiple sclerosis: a paradigm shift.
PURPOSE OF REVIEW: Detailed immunopathological assessment of multiple sclerosis tissue remains the research tool most likely to elucidate the major processes involved in disease pathogenesis and tissue injury. Such studies steer and provide the impetus for refining cellular/molecular investigations and developing more relevant disease models in animals. RECENT FINDINGS: Recent observations in early multiple sclerosis lesions challenge the traditional hypothesis that multiple sclerosis arises as the result of a primary autoimmune process that specifically targets myelin antigen(s). A new multiple sclerosis paradigm proposes that oligodendrocyte apoptosis is the earliest change in newly forming lesions and that tissue injury is amplified by the subsequent recruitment of a systemic immune response. Over months to years the pathology of multiple sclerosis is transformed and the changes which accompany the late phase of the disease suggest that the inflammatory response becomes progressively 'compartmentalized' and therefore largely isolated from systemic influence with time. SUMMARY: Recent pathological studies raise important questions regarding the aetiology of oligodendrocyte apoptosis, the mechanisms by which the accompanying inflammatory response amplifies tissue injury and the regulation of central nervous system immunity. An improved understanding of these processes is essential for advancing therapeutic interventions applicable to different stages of the disease.
Animals↗
Ataxia at altitude measured on a wobble board.
OBJECTIVE: To establish a simple measure of ataxia for use at high altitude. METHODS: Twenty healthy subjects took part in a trek to 5005 m. At 5 different altitudes on the route, they undertook a balance test using a wobble board. The primary objectives were to investigate disturbances of ataxia at altitude and to correlate any observed disturbances with acute mountain sickness (AMS) scores. Secondary outcomes were correlations with cerebral regional oxygenation, pulse oximetry, and age. RESULTS: After a short learning curve, the wobble board test was found to be reproducible. Subjects over 31 years of age were significantly less steady than younger subjects. Subjects suffering acute mountain sickness scored significantly worse on the wobble board test, although scores did not correlate with a specific question on unsteadiness. A positive test defined as equal to or more than 2.5 contacts over 2 minutes gave a predictive value for acute mountain sickness of 66.7% at 4650 m and 100% at 5005 m. Cerebral regional oxygenation in 9 subjects at 5005 m correlated with the wobble board test (r = 0.73; p < .05), whereas pulse oximetry did not. CONCLUSIONS: The wobble board may be a useful adjunct in quantitating ataxia in the field. A positive result may indicate the presence of AMS and may be a useful clinical measure of cerebral hypoxia but should be correlated with other clinical features.
Adult↗
A treatment algorithm for neuropathic pain.
BACKGROUND: Neuropathic pain is a chronic pain syndrome caused by drug-, disease-, or injury-induced damage or destruction of sensory neurons within the dorsal root ganglia of the peripheral nervous system. Characteristic clinical symptoms include the feeling of pins and needles; burning, shooting, and/or stabbing pain with or without throbbing; and numbness. Neuronal hyperexcitability represents the hallmark cellular mechanism involved in the underlying pathophysiology of neuropathic pain. Although the primary goal is to alleviate pain, clinicians recognize that even the most appropriate treatment strategy may be, at best, only able to reduce pain to a more tolerable level. OBJECTIVE: The purpose of this review is to propose a treatment algorithm for neuropathic pain that health care professionals can logically follow and adapt to the specific needs of each patient. The algorithm is intended to serve as a general guide to assist clinicians in optimizing available therapeutic options. METHODS: A comprehensive review of the literature using the PubMed, MEDLINE, Cochrane, and Toxnet databases was conducted to design and develop a novel treatment algorithm for neuropathic pain that encompasses agents from several drug classes, including antidepressants, antiepileptic drugs, topical antineuralgic agents, narcotics, and analgesics, as well as various treatment options for refractory cases. RESULTS: Any of the agents in the first-line drug classes (tricyclic antidepressants, antiepileptic drugs, topical antineuralgics, analgesics) may be used as a starting point in the treatment of neuropathic pain. If a patient does not respond to treatment with at least 3 different agents within a drug class, agents from a second drug class may be tried. When all first-line options have been exhausted, narcotic analgesics or refractory treatment options may provide some benefit. Patients who do not respond to monotherapy with any of the first- or second-line agents may respond to combination therapy or may be candidates for referral to a pain clinic. Because the techniques used at pain clinics tend to be invasive, referrals to these clinics should be reserved for patients who are truly refractory to all forms of pharmacotherapy. CONCLUSIONS: Neuropathic pain continues to be one of the most difficult pain conditions to treat. With the proposed algorithm, clinicians will have a framework from which to design a pain treatment protocol appropriate for each patient. The algorithm will also help streamline referrals to specialized pain clinics, thereby reducing waiting list times for patients who are truly refractory to traditional pharmacotherapy.
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Paraneoplastic neurological syndromes.
PURPOSE OF REVIEW: This review discusses recent advances and current controversies in the aetiology, investigation and management of paraneoplastic neurological syndromes. RECENT FINDINGS: Antibody studies continue to define potential target autoantigens in paraneoplastic neurological syndromes and although pathogenic activity has been demonstrated for anti-glutamate receptor antibodies identified in a subset of patients with cerebellar ataxia, a role for paraneoplastic antibodies in the development of neuronal dysfunction has not been established in the majority of cases. As a result, attention has turned towards clarifying the role of adaptive cellular immunity in the pathogenesis of paraneoplastic neurological syndromes and several studies have defined expanded populations of cytotoxic T lymphocytes specific for epitopes derived from neuronal antigens in patients with paraneoplastic neurological syndromes. In vitro studies demonstrate the potential for antigen-specific cytotoxic T lymphocytes to restrict tumour growth and metastasis, but further investigation is needed to identify the mechanisms by which cytotoxic T lymphocytes could induce neuronal death. Clinical studies have demonstrated that effective tumour treatment can in some instances lead to improvement or stabilization of neurological symptoms. This is an encouraging observation since increased numbers of diagnostic paraneoplastic antibodies can now be reliably tested for and the use of [18F] fluoro-2-deoxyglucose positron emission tomography can facilitate earlier tumour diagnosis in patients presenting with paraneoplastic neurological syndromes. SUMMARY: Advances in the clinical management of patients with paraneoplastic neurological syndromes have occurred despite the fact that in most cases the immune effector mechanisms that lead to the development of neurological dysfunction remain to be characterized.
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The immunopathogenesis of paraneoplastic neurological syndromes.
Paraneoplastic neurological syndromes are rare non-metastatic complications of cancer that have an immune-mediated aetiology. The central and peripheral nervous systems are considered to be immune-privileged sites, since the presence of the 'blood-brain/nerve barrier' means that antigens sequestered within the nervous system do not normally induce an immune response. Aberrant expression of a neuronal antigen by a tumour arising outside this barrier can lead to the breakdown of immune tolerance to the nervous system. However, in many cases the immune mechanisms that result in neurological dysfunction remain poorly defined. Furthermore, aberrant expression of neuronal antigens can be detected in many tumours that are not complicated by non-metastatic neurological syndromes. This review article examines current concepts in the immunopathogenesis of paraneoplastic neurological syndromes.
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