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Biomedical subjects

J D Mitchell

Publications and source records attributed to J D Mitchell.

At least 73 records · Page 4Linked to original sources

Explanation and management of neurological disability.

Patients are often told of the diagnosis of a neurological disability in less than ideal circumstances such that they may not fully comprehend it. Clinicians must be able to sense when the patient's understanding is imperfect even if superficially he or she appears to take in what has been said and its implications. A programme of further counselling is often required to follow this up. A critical look at current procedures will show how these problems arise. It is suggested that improvements in the care of neurologically disabled patients would follow from improved communication between the many agencies that the concerned in their care and from providing books and other material explaining disability and its treatment. A logical development would be for disabled living centres to be established adjacent to existing neuroscience units.

Communication↗

Nucleic acid splicing events occur frequently during macronuclear development in the protozoan Oxytricha nova and involve the elimination of unique DNA.

During its life cycle, the hypotrichous ciliated protozoan Oxytricha nova transforms a copy of its chromosomal micronucleus into a transcriptionally active macronucleus which contains exclusively linear, gene-sized DNA molecules with an average size of about 2.2 kilobase pairs (kbp). The micronuclear precursors of two macronuclear DNA molecules have been examined. Each was found to contain at least five blocks of DNA sequences that are absent in the mature macronuclear DNA molecule. These blocks of sequences, referred to as internal eliminated sequences (IESs), must be removed by a nucleic acid breakage and joining process during development. The data obtained to date indicate that IESs are common and suggest that greater than 60,000 IES removal events occur during macronuclear development. Additional analyses indicate that IESs represent a portion of the unique micronuclear DNA sequences known to be eliminated during development. Comparisons of the sequences of IESs revealed common organizational features and some limited primary sequence homologies that suggest models for their developmental excision.

Animals↗

Indices of free radical activity in the cerebrospinal fluid in motor neuron disease.

Indices of free-radical activity and lipid peroxidation were studied in cerebrospinal fluid samples obtained from 11 patients with motor neuron disease and 11 reference subjects. No differences were found between the two groups. The significance of this finding is discussed in relation to current views of the possible pathogenesis of this disease.

Adult↗

Heavy metals and trace elements in amyotrophic lateral sclerosis.

The first descriptions of the clinical picture of ALS arose from knowledge of the toxic effects of lead on the nervous system. The place of lead in the etiology of ALS remains controversial over 150 years later. More recently, trace element studies have provided a novel approach in our attempts to demonstrate a fundamental metabolic abnormality in motor neurons. The evidence that has been presented in this general area is reviewed in this article.

Amyotrophic Lateral Sclerosis↗

Norethisterone treatment to control timing of the IVF cycle.

The use of norethisterone to control the timing of the preceding menstrual cycle and in consequence the timing of the in-vitro fertilization (IVF) cycle has been evaluated in a therapeutic IVF programme in which oocyte recovery was limited to 2 days each week. A consecutive series of 181 cycles after norethisterone and 29 untreated controls were compared. Menstruation occurred 2-3 days after norethisterone as planned in 82% of patients overall and in 87% of patients whose menstrual cycle length varied by no more than 2 days about the median. Norethisterone treatment did not significantly affect the outcome of IVF treatment compared with the controls in respect to cycles abandoned (12 versus 0%, respectively), peak follicular diameter (mean 18.1 mm versus 18.3 mm 48 h before laparoscopy), oocyte recovery rate (4.6 versus 4.5 per patient), oocyte morphology (63% versus 52% mature), or fertilization rate (72 versus 65% of mature oocytes). Clinical pregnancies were too few for comparison (rates 27 versus 9% per laparoscopy) but the overall rate (23%) indicated effectiveness of the methods. Prior norethisterone treatment appears to be an effective and useful means of controlling the timing of the oocyte recovery in IVF treatment.

Female↗

Identification of relaxin immunoreactivity in human follicular fluid.

Relaxin immunoreactivity has been found in samples of human follicular fluid collected from artificially stimulated pre-ovulatory follicles. The crude extract caused a reduction in the height of the contractions in a rat uterine strip bioassay. The reactive material eluted from Sephadex G50 in two major peaks. The first contained approximately 60% of the immunoreactivity and had an elution position corresponding to that of porcine relaxin, indicating a mol. wt of approximately 6000 daltons. The second peak was of a lower mol. wt, but its exact size and significance are unknown. A possible role for relaxin in the process of follicular rupture is suggested.

Biological Assay↗

Motor neurone disease in the Lothian Region of Scotland 1961-81.

One hundred and sixty one patients with motor neurone disease (MND), from the Lothian Region of Scotland, were studied in an attempt to identify factors important in disease aetiology. Onset of the disease was between 1961 and 1981 and the incidence was highest between 1968 and 1975. The probability of developing MND was greatest between the ages of 65 and 69, and a greater proportion of female patients than of males had onset in the bulbar muscles. Some 5% of patients had a positive family history of MND. There was no evidence that infective agents were important in the aetiology of the disease. There was a suggestion that the patient group contained a greater number of electrical workers, food, drink and tobacco workers, and rubber workers than would have been expected. However, a larger series of patients would be needed to confirm an increased susceptibility to MND in individuals engaged in these occupations.

Adult↗

Trace elements in the spinal cord and other tissues in motor neuron disease.

Trace elements were estimated in the spinal cord, liver and bone of five patients dying of motor neuron disease and five control subjects dying of non-neurological disease. The content of selenium in cord and liver and the cord manganese level were significantly increased in the motor neuron disease patients. These findings are discussed in terms of the possible aetiology of motor neuron disease.

Aged↗

Screening for antimalarial maculopathy in rheumatology clinics.

Ophthalmoscopy and three tests of visual function were undertaken in 39 patients with rheumatoid arthritis receiving treatment with antimalarial drugs and in a control group of 16 patients with rheumatoid arthritis who were not receiving such treatment. Visual contrast sensitivity, macular threshold to red light, and central visual fields to red targets were not significantly different in treated patients and controls. There were no abnormalities in visual acuity, but 11 of 76 eyes of treated patients showed minor macular abnormalities on ophthalmoscopy that were not seen in control patients, suggesting that ophthalmoscopy may be the most sensitive measure of early drug toxicity. Five rheumatologists were able to identify 52 of 65 minor changes detected by an ophthalmologist. These studies, and a critical review of published reports, suggest that in clinical practice antimalarial drugs can be administered safely to patients with rheumatoid arthritis without the need for repetitive routine examination by an ophthalmologist or the use of complicated physiological tests. Recording of visual acuity in each eye and ophthalmoscopy by the prescribing doctor may be all that are required to detect early antimalarial maculopathy.

Adult↗

Endometriosis and ovulatory disorder: reduced fertilisation in vitro compared with tubal and unexplained infertility.

In-vitro fertilisation (IVF) was carried out once for each of 104 couples who had a single cause of infertility. The group with tubal damage was used as the reference for normal fertilising capacity of both oocytes and sperms: the IVF rates were 68% (71/105) per mature oocyte and 88% (37/42) for couples from whom mature oocytes were recovered. Couples with poor sperm/mucus penetration had reduced IVF rates: 32% (12/38) per oocyte and 60% (9/15) per couple. Sperm function, which was judged normal by means of standard seminal analysis and mucus penetration, was confirmed by normal IVF in unexplained infertility: 63% (37/59) per oocyte and 90% (18/20) per couple. Despite favourable sperm function in their partners, women with endometriosis (without tubal damage) had reduced IVF rates: 33% (19/58) per oocyte and 60% (9/15) per couple. These findings indicate that ovulatory disorder is present in endometriosis and suggest that it causes the associated infertility.

Adult↗

Immunological studies on the cerebrospinal fluid in neurological sarcoidosis.

The rate of intrathecal IgG synthesis and the degree of permeability of the blood-brain barrier in 5 patients with sarcoidosis involving the central nervous system are described. Intrathecal IgG synthesis was unusual but increased leakiness of the blood-brain barrier was common in these patients; a finding which may help differentiate such cases from patients with multiple sclerosis.

Albumins↗

Phytanic acid oxidase deficiency in childhood.

Tables 2 and 5 summarize the major clinical and biochemical findings in these patients. Cases 1 and 2 resemble clinically the previous cases of children reported as suffering from infantile phytanic acid storage disease, Zellweger's disease, or neonatal adrenoleucodystrophy. Cases 3 and 4 differ strikingly from these and from one another. Numerous questions remain unanswered, but it seems likely that these patients have in common defects in peroxisomal function which are related but not identical. Why some patients with phytanic acid oxidase deficiency do not have significant elevation of serum phytanic acid is not known. These results, however, make it clear that a normal serum phytanic acid level does not exclude phytanic acid oxidase deficiency. In children with a progressive neurological illness, with liver disease, retinal disease, unexplained neuropathy or deafness, detailed studies of fatty acid metabolism are indicated, including lipoproteins, serum phytanic acid, C26:C22 long-chain fatty acid ratios, serum pipecolic acid and phytanic acid oxidase levels. Electron microscopy of liver biopsy specimens should be considered. Phytanic acid oxidase may prove a useful marker for some of these illnesses, and its usefulness could extend to prenatal diagnosis and assist in genetic counselling.

Abnormalities, Multiple↗