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Biomedical subjects

Neil Gordon

Publications and source records attributed to Neil Gordon.

At least 19 recordsLinked to original sources
PubMed2006

Alpers syndrome: progressive neuronal degeneration of children with liver disease.

Alpers syndrome was not clearly defined until the link between brain and liver disease was described. Alpers syndrome can now be clearly established as a disorder of oxidative metabolism related to mitochondrial dysfunction, and in most instances with an autosomal mode of inheritance. The symptoms and signs are discussed. The illness occurs in the first years of life with the sudden onset of intractable seizures associated with developmental delay, hypotonia, ataxia, cortical blindness, and hepatic failure, and death occurs within a short time. Treating the seizures with valproic acid can cause the rapid onset of liver failure and must be avoided. To establish a definite diagnosis, liver and muscle biopsies may be needed. The former shows bile duct proliferation with the evidence of cirrhosis, and the latter may support the involvement of the mitochondrial respiratory chain if there are ragged-red fibres. Genetic studies can show an association with mitochondrial DNA depletion and mutations in the polymerase gene. Cytochrome c oxidase deficiency has been demonstrated in some patients. Useful diagnostic tests include liver function tests, lactic acid levels in the blood and cerebrospinal fluid, electroencephalograms, computed tomography, and magnetic resonance imaging. The differential diagnosis will be from other forms of neuronal degeneration and disorders of mitochondrial function. There is no specific treatment, which must await further research into causes.

Anticonvulsants↗
PubMed2006

Best practice for obesity and weight management: finding success through linking effective gastric bypass surgery policy and health management.

Obesity is a health issue of epidemic proportions in the United States, creating a health and financial burden for Medicare, Medicaid, and commercial populations alike. While obesity has been linked to an increased risk for any number of health conditions, including heart disease, diabetes, and certain cancers, even a moderate weight loss can mitigate some of the negative medical consequences of unhealthy weight. Obese individuals are often unsuccessful at meeting their weight loss goals for a variety of reasons. Many are increasingly looking to gastric bypass surgery as an easy-fix weight loss solution without fully addressing underlying issues for the original weight gain and failures with previous attempts to lose weight. Because of this, over the past five years an increase in gastric bypass surgeries has resulted in cases with poor outcomes and a subsequent reaction by health plans and employers across the country to eliminate coverage. Others have determined that, while exclusion is not the answer, neither is coverage as standard policies allow. Instead, these groups are opting to implement best practice programs that merge individualized counseling, nutritional education/ planning, and physical activity goals with specific policy changes. Evidence has shown that they are achieving success in managing obesity and its impact on healthcare costs and outcomes.

Benchmarking↗
PubMed2005

Glutaric aciduria types I and II.

Glutaric aciduria type I is an autosomal recessive disorder resulting from a deficiency of glutaryl-CoA dehydrogenase. This leads to an accumulation of glutaric and 3-hydroxyglutaric acids and secondary carnitine deficiency. The symptomatology is discussed, especially those resulting from lesions in the basal ganglia, and the encephalopathic episodes which are often precipitated by infections. The variability of the clinical presentation is stressed. The most serious complications are collections of fluid and blood in the middle fossae, the bleeding resulting from rupture of bridging veins. The prognosis does not seem to be related to the extent of the enzyme deficiency. The diagnosis is confirmed by identifying the abnormal acids in the urine and the deficiency of the enzyme in cultured fibroblasts. The differential diagnosis is reviewed: from other biochemical disorders and from other cerebral lesions. Treatment is by special diet and carnitine supplementation. The dystonia can prove difficult to treat, and surgery may be needed to remove the collections of fluid and blood. Glutaric aciduria type II is caused by a deficiency of either electron transport flavoprotein or of electron transport flavoprotein oxoreductase. The symptoms can be mild or severe. The former may only occur in times of stress, and the latter include congenital anomalies, especially of the kidneys and heart. The pathology of these are discussed. The demonstration of organic acids in the urine and the results of muscle and liver biopsies confirm the diagnosis, and treatment with a special diet and supplementation with carnitine and riboflavine is effective.

Carnitine↗
PubMed2004

Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria).

Succinic semialdehyde dehydrogenase deficiency is one of the disorders of GABA metabolism, so it is not surprising that seizures occur as one of the symptoms in affected patients. Other features that are described include delayed development, hypotonia, myopathy with ragged red fibres, abnormal behaviour, and ocular abnormalities. Neonatal problems include prematurity, respiratory difficulties, and hypoglycaemia. The responsible gene has been identified on the short arm of chromosome 6. There are many mutations, and there is poor genotype-phenotype correlation resulting in difficulties in diagnosis. The pathogenesis of the condition is discussed, especially the results of the disturbed GABA catabolism, and the production of the gamma-hydroxybutyric acid. The many properties of this substance suggest it may act as a neurotransmitter or neuromodulator in the brain. The diagnosis may be difficult as the clinical picture is not really suggestive, but the MRI examination can help if it shows abnormalities in the globus pallidus. It will be confirmed by finding an excess of 4-hydroxybutyric acid in the body fluids; and the methods of estimation are discussed. Prenatal diagnosis is possible using a combination of methods. Treatment possibilities are limited. Vigabatrin should be of value as it is an inhibitor of GABA transaminase, but results have been disappointing. Symptomatic treatment may well be needed for control of seizures, abnormal behaviour and other disorders; and special educational needs must be served.

Aldehyde Oxidoreductases↗
PubMed2004

The neurology of sign language.

Forms of sign language have developed in a number of countries. American Sign Language, which originated from French signing, has been most extensively researched. As sign language is based on gestures executed in space and perceived visually it might be thought that it would mainly be a function of the right cerebral hemisphere when this is the non-dominant one. A number of studies are reviewed showing that sign language is a language in its own right and therefore, as with spoken language, its primary site of organization is in the dominant hemisphere. This does not mean that there is not a significant contribution from the other hemisphere with an interplay between the two. Each research project usually contributes some facet of knowledge apart from the main conclusions. These included the importance of distinguishing signs from gestures, the localization of different types of signing within the left dominant cerebral hemisphere, the fact that lesions of the right non-dominant hemisphere, although not causing a loss of signing will result in dyspraxia, and that aphasic symptoms of signing and speech are not modality dependant but reflected a disruption of language processes common to all languages. Examples are given of discoveries made by the use of the newer neuroradiological techniques such as functional magnetic resonance imaging and positron emission tomography, and no doubt these will lead to further advances in knowledge. The use of sign language in the treatment of patients with verbal aphasia is considered, especially of children with the Landau-Kleffner syndrome, but therapy of this kind can be used in children with delayed language development, and in other types of acquired aphasia at any age. Other methods of treatment than signing, such as cochlear implants may be increasingly used in the future, but it seems likely that sign language will continue to be a dominant feature in the deaf culture.

Aphasia↗
PubMed2003

Alexander disease.

Alexander disease is a rare disorder with limited understanding of its cause, although it does seem to be a disorder of astrocytes rather than a leukodystrophy. It can be divided into three groups: infantile, juvenile, and adult. The infantile type shows enlargement of the head, retarded development and evidence of a severe neurological disorder. The juvenile sufferers are more likely to exhibit bulbar signs, and may not be significantly retarded. Among adults the condition can fluctuate, and so mimic multiple sclerosis. The differential diagnosis in these three groups is discussed, especially the unusual ways in which they can present. The definitive diagnosis may depend on demonstrating Rosenthal fibres in a brain biopsy, or at autopsy, but other tests can be suggestive. The cerebrospinal fluid can show an elevation of B-crystallin and heat shock protein, and the GFAP gene is considered a reliable marker. The EEG and magnetic imaging findings are non-specific. Pathological studies of the brain can be characteristic with demyelination, especially in the frontal lobes, and Rosenthal fibres concentrated in the subpial and subependymal areas. It is possible that these fibres cause a dysfunction of the astrocytes. The genetic investigations are reviewed, and possible causes are discussed. These remain theoretical, but it has been suggested that the disorder is a response to stress from some unknown stimulus. Rosenthal fibres seem to be the result of the condition, although they may be related to the aetiology. There is no specific treatment.

Adult↗
PubMed2003

Iron deficiency and the intellect.

Children are especially liable to iron-deficiency anaemia in developing countries, and in the inner cities of developed countries. Does the lack of iron cause impaired physical and mental development, and can this in certain circumstances be a permanent effect? One of the reasons that this is such a difficult question to answer is that there can be so many confounding factors, from other nutritional deficiencies, to helminthic infections and malaria in tropical countries. If there is a definite relationship, children in the first 2 years of life will be at particular risk during the mayor spurt of brain growth. Lack of iron can affect brain cells, myelin, or neurotransmitters, so there is certainly a theoretical basis for possible brain damage, or there could be an effect from lack of oxygen. Also anaemic children are likely to feel ill and unwilling to co-operate with tests to assess for developmental defects. Many studies of the possible results of iron deficiency on the development of children have been carried out in various countries, and some of these from 1983 onwards are recorded. It is difficult to draw conclusions from these trials, partly due to the variability in their construction, but on balance the evidence suggests that treatment of iron deficiency is justifiable, whether this is associated with anaemia or not. It is equally important to stress the importance of prevention, although more research is needed on the best method to use, which is both effective and affordable.

Anemia, Iron-Deficiency↗
PubMed2003

Glucose transporter type1 (GLUT-1) deficiency.

Glucose transporter type1 (GLUT-1) deficiency may be rare, but it is a preventable cause of severe learning difficulties; and therefore there is an urgency in making an early diagnosis. Suspicions must be roused when intractable seizures occur in infancy. These may be associated with acquired microcephaly and developmental delay. The finding of low glucose sugar levels in the cerebrospinal fluid, but not in the blood will identify the condition. The gene encoding the GLUT-1 protein is located on the short arm of chromosome 1, and inheritance is by a dominant trait. Patients with this syndrome can have heterozygous mutations, with one allele being a normal wild type and one being mutant. An efficient transport of glucose across the blood-brain barrier is essential as it is such an important fuel for the brain, and this is provided by glucose transporter type1 in the endothelial cells of the brain capillaries. Another minor contribution to the symptomatology of GLUT-1 may be impaired transport of an oxidised form of vitamin C. Treatment with anti-epileptic drugs may be needed, and the ketogenic diet may reduce symptoms, as ketosis can provide an alternative source of fuel for the brain. It has also been suggested that antioxidant thioctic acid may be of benefit. Substances such as caffeine and phenobarbitone should be avoided as they inhibit glucose transport.

Anticonvulsants↗
PubMed2003

Ornithine transcarbamylase deficiency: a urea cycle defect.

The symptoms and signs of ornithine transcarbamylase deficiency are discussed. When the condition occurs among males in the neonatal period it is likely to be lethal. Pathological findings are non-specific. The diagnosis should be considered if coma with cerebral oedema and respiratory alkalosis occurs for no obvious reason. When hyperammonaemia is found, enzyme assay on a liver biopsy should be considered. A useful clue in an asymptomatic patient is a voluntary adoption of a vegetarian diet. Provocative tests, such as the allopurinol test can be used, but the method most frequently applied is mutation analysis. In the case of prenatal diagnosis this is possible on a chorionic villus sample. The prognosis of ornithine transcarbamylase deficiency is better for those with an onset after infancy, but morbidity from brain damage does not appear to be linked to the number of episodes of hyperammonaemia that have occurred. The syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase which catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. The gene responsible for this enzyme is located on Xp21.1, and is expressed in the liver and gut. Mutations can be divided into two groups: those with neonatal onset with all enzyme activity abolished, and those with later onset with partial and varying enzyme deficiency. There can be a variety of precipitating causes, for example sodium valproate. Treatment can be given with a low protein diet, and with alternate pathway drugs such as sodium benzoate and phenylbutyrate. Liver transplant can be considered when symptoms are life-threatening, although there may be severe complications.Gene replacement therapy is the hope of the future.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Huntington's disease of early onset or juvenile Huntington's disease.

The presentation of juvenile Huntington's disease can cause diagnostic difficulties. The genetics and pathogenesis of the condition are discussed. The diagnosis will depend on the symptoms raising suspicions and the exclusion of other disorders, especially by genetic studies.

Adolescent↗
PubMed2002

Sleep apnoea in infancy and childhood. Considering two possible causes: obstruction and neuromuscular disorders.

Two aspects of sleep apnoea in infancy and childhood are considered. First of all the obstructive sleep apnoea syndrome is reviewed; its causes, and types, and clinical differences depending on the age of the affected patient. Difficulties of diagnosis are discussed, as well as methods used to confirm the presence of the syndrome. Then means of treatment are considered, both medical and surgical. The second part of the paper is concerned with a particular group of children, especially at risk of sleep apnoea; those suffering from neuromuscular disorders as these are likely to be of special interest to paediatric neurologists. These include neuropathies, myopathies such as Duchenne muscular dystrophy and myotonia, and disorders of the neuromuscular junction.

Airway Obstruction↗