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Biomedical subjects

P Eldridge

Publications and source records attributed to P Eldridge.

16 recordsLinked to original sources

Autologous transplantation of CD133 selected hematopoietic progenitor cells for treatment of relapsed acute lymphoblastic leukemia.

A 21-year-old white male with relapsed acute lymphoblastic leukemia (ALL) developed an invasive Zygomycosis infection 3 weeks after beginning re-induction chemotherapy. Because of the high risk of fatal recurrence of the fungal infection, neither long-term maintenance chemotherapy nor allogeneic hematopoietic stem cell transplant (HSCT) was considered appropriate. Because his ALL blasts expressed CD34 but lacked CD133, he received a CD133 selected autologous graft following high-dose consolidation chemotherapy. The patient survives in remission 19 months after HSCT.

AC133 Antigen↗

The seizure outcome after amygdalohippocampectomy and temporal lobectomy.

The aim of this study was to compare the seizure outcome of two different types of epilepsy surgery, selective amygdalohippocampectomy (AHE) and anterior temporal lobectomy (ATLE) in patients with temporal lobe epilepsy. We included 114 patients who had mesio-temporal lobe epilepsy and hippocampal sclerosis or gliosis on histology. Patients had ATLE if the non-dominant hemisphere was affected or if the whole temporal lobe was atrophic. Patients had AHE if the dominant hemisphere was affected. Standardized seizure outcome at 1 year following surgery was used. Overall 40% of the 114 patients who had temporal lobe epilepsy surgery were seizure-free at 1-year (Engel's class Ia). A good outcome (Engel's classes I and II) was significantly more frequent in ATLE than in AHE. (66% and 44%, respectively, P = 0.03). ATLE had a better seizure outcome than AHE.

Adolescent↗

Fish odour syndrome with features of both primary and secondary trimethylaminuria.

We report a patient with the fish odour syndrome who has both primary and secondary trimethylaminuria. The diagnosis was made using biochemical and genetic analysis in the apparent absence of any characteristic smell. Differentiation of primary and secondary trimethylaminuria is usually made on urinary analysis of trimethylamine and its metabolite trimethylamine N-oxide, with different, characteristic patterns of both compounds in primary and secondary trimethylaminuria. Our patient had biochemical analysis consistent with a diagnosis of secondary trimethylaminuria, while analysis of the flavin-containing mono-oxygenase 3 gene, the causative gene in primary trimethylaminuria, demonstrated three sequence polymorphisms, two of which are known to reduce enzyme activity. The patient showed temporary clinical and biochemical response to treatment with metronidazole and neomycin. It is important to be aware of this diagnosis in patients without obvious clinical signs, and of the subjective benefits of treatment.

Biomarkers↗

Artifactually low glycated haemoglobin in a patient with severe hypertriglyceridaemia.

This report describes a case of artifactually low glycated haemoglobin (Hb) in a patient with type II diabetes and severe hypertriglyceridaemia. The effect of hypertriglyceridaemia on glycated Hb determination using the Abbott Vision method was investigated in a series of patients with diabetes. The interference of triglycerides in glycated Hb assays was also investigated by two other methods, the Beckman Synchron CX4 delta immunoturbidimetric method, and the Primus affinity chromatography high performance liquid chromatography assay.

Artifacts↗

Screening for hypercholesterolaemia in 10,000 neonates in a multi-ethnic population.

UNLABELLED: An immunoassay was developed for the detection of hypercholesterolaemia in dried blood spots collected from 6-day-old neonates. Blood spot samples (9,673) were subjected to immunoturbidimetric assay to determine the levels of apolipoprotein B (apoB), an index of plasma low density lipoprotein, and of apolipoprotein A-1 (apoA-1), an index of plasma high density lipoprotein. Infants with raised apoB or a reduced apoA-1/apoB ratio were recalled, retested and, if appropriate, referred to the Vascular Risk Clinic at King's College Hospital for medical management. A total of 189 were recalled for further testing; of whom 82 (45%) attended the recall clinic. A group of 16 families (24 individuals) had abnormal lipid profiles; of these, 7 families (14 individuals) had lipid profiles consistent with inherited hypercholesterolaemia. CONCLUSION: Neonatal screening for hypercholesterolaemia using blood spot apolipoprotein measurements is feasible but ethnic variations in disease prevalence must be considered in the design of a screening programme.

Adult↗

Automatic detection of hippocampal atrophy on magnetic resonance images.

An automatic method for identifying hippocampal atrophy on magnetic resonance (MR) images obtained from patients with clinical evidence of temporal lobe epilepsy (TLE) is described. The method is based on the analysis of image intensity differences between patients and controls within a volume of interest (VOI) centred on the hippocampus. The core of the method is a fully automatic signal intensity-based inter-subject image registration technique. In particular, a global affine registration to a reference image is performed, followed by a local affine registration within the VOI. A mask produced by manual segmentation of the mean hippocampus for 30 control subjects enabled investigations to be restricted to a specified region of the VOI approximately corresponding to the hippocampus. Normal variations of hippocampal signal intensity were computed from images obtained for the 30 control subjects. The manual method of hippocampal volumetry, currently an important component of the pre-surgical evaluation of patients with clinical evidence of medically intractable TLE, is used to determine the lower 1st percentile limits of normal hippocampal volume. Hippocampi with volumes below this limit are defined as atrophic. We investigated whether the automatic method can correctly distinguish between 15 patients with significant hippocampal atrophy according to absolute volumes and a further 14 controls. ROC curves enabled evaluation of sensitivity and specificity in respect of an intensity threshold. 100% specificity is required when determining suitability of patients for neurosurgery, resulting in levels of 50% and 70% sensitivity in detecting atrophy in the right and left hippocampus, respectively. We propose that the method can be developed as an automatic screening procedure.

Adolescent↗

Monoclonal antibodies against vascular endothelial antigens expressed in normal human brain.

A panel of monoclonal antibodies reactive with human-brain vessels was raised by immunizing BALB/c mice with homogenate of whole human brain, obtained from temporal lobectomies. Hybridoma supernates were screened by immunohistochemical methods on frozen sections of human brain, liver and spleen and 16 clones were isolated. The pattern of immunoreactivity varied with respect to the type of brain blood vessels predominantly labelled and to tissue specificity. Some antibodies cross-reacted with cow or squirrel monkey forebrain microvessels with an intensity equal to that shown by human brain. The immunoreactivity patterns reflected antigenic heterogeneity among different subsets of vascular endothelial cells in human brain.

Animals↗

Recovery of nerve conduction following microvascular decompression for trigeminal neuralgia.

OBJECTIVE: To assess the function of trigeminal nerve before and after microvascular decompression for trigeminal neuralgia. BACKGROUND: To date there is no direct evidence that microvascular decompression of the trigeminal root restores normal conduction in the nerve. METHODS: The authors examined 10 patients with trigeminal neuralgia in whom preoperative MRI and MR angiography demonstrated neurovascular contact. During microvascular decompression, the trigeminal nerve was monitored by recording early scalp trigeminal evoked potentials immediately before, during, and after decompression. Direct recordings from the root entry zone were also performed. RESULTS: In all patients preoperative scalp evoked potentials showed impaired conduction of the trigeminal root. Microvascular decompression was associated with immediate recovery of conduction in seven patients, demonstrated by both scalp evoked potentials and direct root recordings. All 10 patients were pain free postoperatively. CONCLUSIONS: Improvement in trigeminal neuralgia following microvascular decompression is often associated with normalization of neurophysiologic data, suggesting recovery of nerve function. Rapid electrophysiologic recovery and pain relief following microvascular decompression argue that neither phenomenon is linked to remyelination. It is possible that the trigeminal evoked potentials might predict an effective microvascular decompression.

Decompression, Surgical↗

Impact of incomplete coverage of neonatal dried blood spot screening on estimating HIV-1 seroprevalence.

The aim of this study was to determine the extent to which selective under-coverage of births to mothers more likely to be at risk of HIV-1 infection will result in a significant under-estimation of the true neonatal seroprevalence. Census data, local birth statistics, maternity data and data from the prevalence monitoring programme were used to produce a model to predict the effects of under-coverage in the uptake of neonatal metabolic screening which has been observed in babies with a mother of ethnic group black African. The adjustment factor which allows for under-coverage is the relative inclusion ratio (RIR); the probability that samples from a group at different risk of HIV infection were included in the survey divided by the probability of inclusion for samples from all other babies. The RIR was found to be close to unity (0.97), indicating a minimal bias. Under usual conditions only if the relative inclusion ratio (RIR) declined to values of 0.87 or below would there be a substantial bias. Despite some selective under representation, the results obtained from the Unlinked Anonymous HIV Monitoring Programme Dried Blood Spot Survey would seem to identify levels of prevalence in the population of child-bearing women with a good degree of accuracy and remains a useful tool for resource allocation, planning of services, provision of care and counselling.

Adolescent↗

Variation in coverage by ethnic group of neonatal (Guthrie) screening programme in south London.

OBJECTIVES: To determine whether coverage of the neonatal (Guthrie) screening programme in Britain is different for groups at highest risk of sickle cell disease and to identify possible reasons for incomplete coverage. DESIGN: Descriptive study of coverage of screening programme and its variation by mobility, district of residence, and ethnic group. SUBJECTS: 1727 infants born between 1 October and 31 December 1991. SETTING: Former West Lambeth and Camberwell District Health Authorities, London. MAIN OUTCOME MEASURE: Proportion of infants with an identifiable screening test result. RESULTS: Screening covered 1663/1727 (96.3%) infants overall (745/786 (94.8%) in West Lambeth; 918/941 (97.6%) in Camberwell). The relative odds ratio of an African infant not having been tested compared with a white infant was 3.05 (95% confidence interval 1.30 to 7.14) (2.08 (0.86 to 5.01) after adjustment for mobility and district of residence). For infants whose families moved into the districts after the birth compared with those born and resident in the districts the relative odds ratio of having been tested was 10.16 (4.85 to 21.29). The odds ratio of locally delivered infants in West Lambeth not having been tested compared with those in Camberwell was 2.12 (1.08 to 4.16) after adjustment for ethnic group. CONCLUSION: Coverage of the screening programme is incomplete and poorer in infants of African ethnic group than in white infants. Poorer coverage is also associated with mobility of the family around the time of birth. The findings have implications for using the neonatal programme for testing for sickle cell disease and other disorders. Arrangements for monitoring the existing screening programme are inadequate and an improved system should be established, similar to the scheme that monitors the immunisation programme.

Africa↗

A simple flowmeter for unusual gases.

A flowmeter is described which may be used to measure gas flow in experimental situations. It may be adapted for use with any gas or gas mixture and be used to provide flows as small as 50 ml min-1. A mercury-in-glass manometer (sphygmomanometer) is used to measure the gas pressure proximal to a flow restrictor (consisting of a hypodermic needle hub) and it is this pressure head which, for a given gas, dictates the flow produced. This device may be produced at minimal cost in any hospital, is easy to calibrate and accurate.

Anesthetics↗

Molecular basis of the cell-surface expression of immunoglobulin mu chain without light chain in human B lymphocytes.

Four distinct human B-lymphoid cell lines possess the ability to circumvent the mechanism regulating intracellular transport of immunoglobulin protein. These cells do not produce light chains, yet they express mu heavy chains on the cell surface at comparable levels to B-cell lines that produce native forms of both proteins. The mu-chain mRNA produced in all four cell lines was found to contain an identical deletion of most of the heavy-chain variable (VH) region (75% of the 3' portion), with no apparent alteration in constant (C) region structure. The truncated mu (mu*)-chain mRNA in these cells was created through the use of a cryptic splice donor site found within the human VH gene(s) utilized by these B-cell lines. The truncated mu chains exhibited a decreased ability to associate with the intracellular transport regulatory protein, heavy-chain binding protein (BiP). This result indicates that VH region structure, in addition to C mu 1 region structure, influences the formation of the BiP recognition site on the heavy chain. Furthermore, it suggests that the mechanism allowing for cell-surface expression of the mu* chains in the absence of light-chain pairing is the inability of BiP to bind to the mu* chains and hence prevent their intracellular transport. The high frequency with which the mu-only surface immunoglobulin positive phenotype is present in our collection of human B-cell lines and the isolation of one of the cell lines from a healthy individual also suggest that B cells of this type may represent a significant subpopulation among the normal human B-cell repertoire.

B-Lymphocytes↗