Iodine and neuropsychological development.
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The establishment of the essential link among iodine deficiency, thyroid function and brain development has emerged from a fascinating combination of clinical, epidemiologic and experimental studies. The central human phenomenon that focuses this relationship is the condition of endemic cretinism, described from the Middle Ages and characterized in its fully developed form by severe brain damage, deaf mutism and a spastic state of the hands and feet. The demonstration of the prevention of cretinism in a double-blind controlled trial with injections of iodized oil in Papua New Guinea (1966-1970) established the causal role of iodine deficiency in cretinism by an effect on the developing fetal brain. Cretinism could not be prevented unless the iodized oil was given before pregnancy. Iodine deficiency is now regarded by the WHO as the most common preventable cause of brain damage in the world today, with at least 30 million suffering from this preventable condition. Since 1986 the international NGO, the International Council for Control of Iodine Deficiency Disorders, has worked closely as an expert group with WHO and UNICEF in assisting countries with a program of universal salt iodization for the elimination of iodine deficiency as a cause of brain damage by the year 2000. In 1996, WHO reported that 56% of the population of 83 developing countries now had adequate access to iodized salt. This represents an increase of 750 million since 1990 with protection of 12 million children. (+info)
Nonsuppurative meningoencephalitis associated with Aleutian mink disease parvovirus infection in ranch mink.
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Severe nonsuppurative meningoencephalitis associated with Aleutian mink disease parvovirus (ADV) infection was observed in adult ranch mink. Brain lesions included severe, locally extensive to coalescing lymphoplasmacytic meningoencephalitis with accompanying gliosis, satellitosis, and mild extension of inflammation into the leptomeninges. ADV was identified in mesenteric lymph node, spleen, brain, and liver of affected mink by polymerase chain reaction techniques. Sequences of the ADV isolate (TH5) revealed 2 unique residues in the region of the viral genome that determines pathogenicity. These findings suggest that certain strains of ADV may preferentially cause disease in the nervous system. ADV infection should be considered in the differential diagnosis of neurologic disorders in mink. (+info)
The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK.
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Over an 18-month period, all incident cases of neurological disorders were ascertained prospectively in an unselected urban population based in 13 general practices in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery. In three of these practices, the lifetime prevalence of neurological disorders was also assessed. A population of 100 230 patients registered with participating general practices was followed prospectively for the onset of neurological disorders. Multiple methods of case finding were used to maintain accuracy. The age- and sex-adjusted incidence rates of neurological disorders were calculated. The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients. The age- and sex-adjusted incidence rates were calculated for major neurological conditions. [These are expressed as rates per 100 000 persons per annum, with 95% confidence intervals (CI) in parentheses]. The commonest of these were first cerebrovascular events, 205 (CI: 183, 230); shingles, 140 (CI: 104, 184); diabetic polyneuropathy, 54 (CI: 33, 83); compressive neuropathies, 49 (CI: 39, 61); epilepsy, 46 (CI: 36, 60); Parkinson's disease, 19 (CI: 12, 27); peripheral neuropathies, 15 (CI: 9, 23); CNS infections, 12 (CI: 5, 13); post-herpetic neuralgia, 11 (CI: 6, 17); and major neurological injuries, 10 (CI: 4, 11). Lifetime prevalence rates are also reported (expressed as rate per 1000 persons with 95% CI). The most prevalent conditions were: completed stroke, 9 (CI: 8, 11); transient ischaemic attacks, 5 (CI: 4, 6); active epilepsy, 4 (CI: 4, 5); congenital neurological deficit, 3 (CI: 3, 4); Parkinson's disease, 2 (CI: 1, 3); multiple sclerosis, 2 (CI: 2, 3); diabetic polyneuropathy, 2 (CI: 1, 3); compressive mononeuropathies, 2 (CI: 2, 3); and sub-arachnoid haemorrhage, 1 (CI: 0.8, 2). Overall, the onset of 625 neurological disorders was observed per 100 000 population annually. Six percent of the population had at some time had a neurological disorder. This is the first study of the incidence and lifetime prevalence of neurological disorders in recent times; we found that these disorders give rise to significant morbidity in the community. (+info)
Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies.
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Many data point to a pathogenetic role for IgM antibodies to the myelin-associated glycoprotein (MAG) in the neuropathy associated with IgM monoclonal gammopathy, supporting the use of immune therapies in affected patients. Almost 50% of patients have been reported to improve with these therapies, but the effect of treatment on the long-term prognosis of the neuropathy remains unclear. We analysed the outcome of 25 of the 26 patients (mean age at entry 65 years, range 45-85 years) with neuropathy and high anti-MAG IgM, first examined by us between 1984 and 1994. By January 1999, after a mean follow-up of 8.5 years (range 2-13 years) and a mean duration of neuropathy symptoms of 11.8 years (range 3-18, >10 years in 16), 17 patients (68%) (aged 58-84 years, mean 73.4) were alive, while eight (32%) (aged 69-78 years, mean 73.1) had died 3-15 years (mean 10.6) after neuropathy onset; in none of them was death caused by the neuropathy, although in three it was possibly related to the therapy for the neuropathy. By the time of last follow-up or patients' death, 11 patients (44%) were disabled by severe hand tremor, gait ataxia or both. The disability rates at 5, 10 and 15 years from neuropathy onset were 16, 24 and 50%, respectively. Of the 19 patients treated during the follow-up for 0.5-11 years (mean 4 years) with various immune therapies, five reported a consistent and four a slight improvement in the neuropathy (total 47%) after one treatment or more, but in only one patient was improvement persistent throughout, to the end of follow-up. In 10 patients (53%), severe adverse events, possibly related to therapy, occurred during treatment and were considered responsible for the patient's death in three. The neurological impairment did not differ between treated and untreated patients at the end of a similar follow-up. Our findings indicate that (i) the majority of patients with neuropathy and anti-MAG IgM have a favourable prognosis even after several years, and (ii) current immune therapies, though temporarily effective in half of the patients, are associated with considerable side effects which limit their prolonged use and efficacy, suggesting that until more effective or safer therapies become available, they should probably be reserved for patients impaired in their daily life or in a progressive phase of the disease. (+info)
Glutamate as a neurotransmitter in the brain: review of physiology and pathology.
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Glutamate is the principal excitatory neurotransmitter in brain. Our knowledge of the glutamatergic synapse has advanced enormously in the last 10 years, primarily through application of molecular biological techniques to the study of glutamate receptors and transporters. There are three families of ionotropic receptors with intrinsic cation permeable channels [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate]. There are three groups of metabotropic, G protein-coupled glutamate receptors (mGluR) that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Glutamate is the most abundant amino acid in the diet. There is no evidence for brain damage in humans resulting from dietary glutamate. A kainate analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate, by activating NMDA, AMPA or mGluR1 receptors, may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis. (+info)
Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
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Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula neritina in 1982 and is currently undergoing evaluation in a number of malignancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymphoma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h continuous infusion every 2 weeks at a dose of 120 microg/m2 per course. Patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion. The dose of vincristine was escalated in groups of three patients as follows: level 1, 0.5 mg/m2; level 2, 1.0 mg/m2; and level 3, 1.4 mg/m2 with vincristine doses capped at 2.0 mg for all patients. Bryostatin 1 alone resulted in one complete remission and two partial remissions. Nine patients received sequential treatment with bryostatin 1 and vincristine. The addition of vincristine at a dose of 2 mg was feasible and caused the expected dose-related sensory neuropathy. Phenotypic analysis by flow cytometric analysis on pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed up-regulation in the coexpression of CD11c/ CD22 on CD20+ B cells in two of four CLL patients studied, which is consistent with in vitro findings of differentiation of CLL cells to a hairy cell phenotype. (+info)
Neurobehavioral toxicity.
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A growing number of agents are known to perturb one or more of the interconnected processes of the central nervous system. At the same time, there is an increase in the incidence of neurobehavioral disorders that are confronting clinicians with baffling symptoms and presentations that seem uncommon. Fundamental to the assessment of the environmental-relatedness of the syndromes is a work and exposure history, including information different from that routinely obtained in the clinical setting. Exposure examples are described to suggest the scope of inquiry necessary to differentiate neurotoxic syndromes from nonneurotoxic illness. (+info)
Brain function in the elderly: role of vitamin B12 and folate.
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Vitamin B12 (cobalamin) deficiency associated neuropathy, originally called subacute combined degeneration, is particularly common in the elderly. The potential danger today is that with supplementation with folic acid of dietary staples such as flour, that the incidence of this disease could rise as folic acid, as opposed to natural folate (N5CH3HFGlu1), enters the cell and the metabolic cycle by a cobalamin independent pathway. This chapter briefly describes the clinical presentation of the disease, which unless treated will induce permanent CNS damage. The biochemical basis of the interrelationship between folate and cobalamin is the maintenance of two functions, nucleic acid synthesis and the methylation reactions. The latter is particularly important in the brain and relies especially on maintaining the concentration of S-adenosylmethionine (SAM) which, in turn, maintains the methylation reactions whose inhibition is considered to cause cobalamin deficiency associated neuropathy. SAM mediated methylation reactions are inhibited by its product S-adenosylhomocysteine (SAH). This occurs when cobalamin is deficient and, as a result, methionine synthase is inhibited causing a rise of both homocysteine and SAH. Other potential pathogenic processes related to the toxic effects of homocysteine are direct damage to the vascular endothelium and inhibition of N-methyl-D-aspartate receptors. (+info)