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Biomedical subjects

J Palace

Publications and source records attributed to J Palace.

13 recordsLinked to original sources
PubMed1997

Incidence of serum anti-P/O-type and anti-N-type calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome.

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which autoantibodies are directed against voltage-gated calcium channels (VGCCs) at presynaptic nerve terminals. We first demonstrated the presence of P/Q-type and N-type VGCCs in digitonin extracts prepared from human and rabbit cerebellum using the specific ligands 125I-omega-conotoxin MVIIC (125I-omega-CmTx) and 125I-omega-conotoxin GVIA (125I-omega-CgTx), respectively. We then tested sera from 72 LEMS patients' 25 with proven small cell lung cancer (SCLC) and 66 healthy or other neurological, SCLC or autoimmune disease controls in an immunoprecipitation assay using 125I-omega-CmTx-labelled (P/Q-type) VGCCs in human cerebellar extract. Sixty-six of 72 LEMS serum samples (91.7%) were positive for the presence of VGCC antibodies, as defined as a titre greater than 3 standard deviations above the mean for the healthy controls (n = 22). Rabbit cerebellar extract as antigen gave similar results (r = 0.94, P < 0.001, n = 30). By contrast, only 24/72 (33%) LEMS sera were positive in the assay for anti-N-type VGCC antibodies using 125I-omega-CgTx. All these 24 were also positive in the 125I-omega-CmTx assay. All healthy and disease control sera were negative in both assays. The anti-P/Q-type VGCC antibody titres did not correlate with an electrophysiological index of disease severity across individuals; however, longitudinal studies in a LEMS patient with SCLC receiving chemotherapy, and in a non-SCLC LEMS patient receiving immunosuppressive therapy showed an inverse relation between antibody titre and disease severity. These results support the view that anti-P/Q-type VGCC antibodies are implicated in the motor disorder in LEMS, and show that the omega-CmTx radioimmunoassay is a highly specific and sensitive means of detecting them.

Adolescent↗
PubMed1997

How to recognize patients with parkinsonism who should not have urological surgery.

OBJECTIVE: To examine whether there are urogenital criteria that the urologist could apply to a patient with idiopathic Parkinson's disease (IPD) and bladder symptoms, and so avoid operating on patients with multiple system atrophy (MSA). PATIENTS AND METHODS: The clinical features of 52 patients with probable MSA and 41 patients with IPD were studied retrospectively with particular attention to the nature of lower urinary tract symptoms and erectile dysfunction in relation to the onset of parkinsonism. Anal sphincter electromyography (EMG) was recorded in all the patients with MSA and in 12 of the patients with IPD. RESULTS: Of the patients with MSA, 60% had urinary symptoms preceding or presenting with IPD but in 94% of the patients with IPD the neurological diagnosis preceded the onset of urogenital symptoms. Most of the patients with MSA (73%) had troublesome urinary incontinence whereas the majority of those with IPD (85%) had urgency and frequency but were not incontinent; 66% of the patients with MSA and 16% of patients with IPD had a significant post-void residual volume. Of the men with MSA, 93% had erectile dysfunction and in 48% of them this complaint preceded the diagnosis of MSA. All 11 men with MSA who had a TURP were incontinent post-operatively. CONCLUSION: The urogenital criteria which favour a diagnosis of MSA are: (i) urinary symptoms preceding or presenting with parkinsonism; (ii) urinary incontinence and IPD; (iii) a significant post-void residual urine volume; (iv) erectile failure preceding or presenting with parkinsonism; and (v) worsening bladder control after urological surgery. Patients with parkinsonism and these features should be offered medical management rather than urological surgery.

Electromyography↗
PubMed1997

Congenital myasthenic syndromes.

Congenital myasthenic syndromes are a rare group of heterogeneous disorders affecting neuromuscular transmission. Recent identification and in-vitro functional analysis of some of the genetic mutations that cause these disorders correlates with previous electrophysiological, biochemical, pathological and therapeutic studies, and has advanced our understanding of neuromuscular transmission.

DNA Mutational Analysis↗
PubMed1996

Memory in myasthenia gravis: neuropsychological tests of central cholinergic function before and after effective immunologic treatment.

There are reports of central cholinergic deficits in myasthenia gravis (MG) describing impaired performance on a variety of tests of memory with varying benefits from plasmapheresis. We tested 11 patients with symptomatic MG at the start of a trial of immunosuppressive treatment (prednisolone plus azathioprine or placebo) and again when in remission. The tests included the Logical Memory and Design Reproduction parts of the Wechsler Memory Scale, the Rey Auditory Verbal Learning Test, Peterson-Peterson task, and an auditory vigilance task. Muscle strength improved significantly over the period of treatment, but overall performance on tests of memory or attention did not. These results fail to substantiate reports of functionally significant and reversible central deficits in myasthenia gravis.

Adolescent↗
PubMed1994

Immunogenicity of human recombinant acetylcholine receptor alpha subunit: cytoplasmic epitopes dominate the antibody response in four mouse strains.

In mysathenia gravis (MG) autoantibodies directed against acetylcholine receptors (AChR), at the neuromuscular junction lead to muscle weakness. These antibodies are directed against extracellular determinants, predominantly on the AChR alpha subunits. Similar antibodies can be induced in animals by immunisation with purified AChR, but immunisation of mice with recombinant human alpha subunit or its extracellular domain has produced conflicting results. To study further the immunogenicity of the human alpha subunit we immunised four inbred stains (C57B1/6, SJL, BALB/c, SWR) with almost full-length recombinant alpha subunit, r37-429, and looked at B cell epitopes by mapping with smaller recombinant fragments and synthetic peptides. The majority of anti-r37-429 antibodies bound to sequences within a region thought to be cytoplasmic, alpha 325-368, and reacted with human AChR. In two C57B1/6 sera, only, most antibodies were directed against an extracellular region, alpha 138-167, but the r37-429 used for immunisation of these two mice appeared to have lost the integrity of its cytoplasmic domain during preparation. Our results suggest that the antigenicity of the cytoplasmic region of the recombinant alpha subunit dominates the immune response in each of the four strains, and may even suppress the formation of antibodies to the extracellular domain. Moreover, although C57B1/6 and SJL mice were able to produce antibodies to alpha 138-167, these antibodies did not react with intact AChR, and none of the mice became weak.

Amino Acid Sequence↗
PubMed1991

3,4-Diaminopyridine in the treatment of congenital (hereditary) myasthenia.

Congenital or hereditary myasthenia describes a heterogeneous group of disorders in which the immune system is not implicated. Treatment has previously depended on anticholinesterase medication. The effectiveness of 3,4-diaminopyridine (3,4-DAP), a preparation that enhances acetylcholine release from motor nerve terminals, has been evaluated using a series of standardised strength measures. Sixteen patients (aged seven to 47 years) were studied in an open prospective trial, and four of them in a double blind crossover trial; existing anticholinesterase medication was continued. For the group as a whole, there was a highly significant increase in muscle strength (p less than 0.001; n = 16). In individual paired comparisons, 13 out of 16 showed significant improvement in the open trial and four out of four in the blind crossover trial. In conclusion, 3,4-DAP, either alone or combined with anticholinesterase medication, may be a useful additional treatment in congenital myasthenia.

4-Aminopyridine↗
PubMed1987

Cryptococcal choroidoretinitis and immunodeficiency.

A 30 year old man with Hodgkin's disease, clinically in remission, presented with blurred vision in one eye due to a choroiditis. He developed headaches 10 days after commencing oral steroids and was subsequently found to have cryptococcal meningitis. The meningitis and choroiditis resolved on antifungal medication. This is the first case of cryptococcal choroiditis recorded in the United Kingdom.

Adult↗