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Biomedical subjects

B Harding

Publications and source records attributed to B Harding.

At least 19 recordsLinked to original sources
PubMed1992

Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease.

Fazio-Londe disease is a label sometimes applied to a degenerative disease of the motor neurons characterized by progressive bulbar paralysis in children. It is very rare with only 22 case reports describing 24 children including four sibling pairs. In two reports mothers and sons were affected. The neuropathology is described in only four cases. Previous authors have recognized that the condition is very heterogeneous. The clinical features of five children with this type of progressive bulbar paralysis, diagnosed at this hospital between 1969 and 1989, are reviewed, and in two cases neuropathological findings are detailed. Based on this experience, suggested criteria for diagnosis include clinical features of a pure motor neuronopathy affecting the bulbar nuclei, exclusion of other causes of progressive bulbar paralysis and positive support for the diagnosis from electromyography and/or pathological examination. A review of the literature, combined with the present series, suggests that there are at least three distinct subtypes: a very rare autosomal dominant form (as described by Fazio) and two variants with probable autosomal recessive inheritance either with early onset of respiratory symptoms and rapid progression to death or later onset, less prominent respiratory symptoms and protracted clinical course. There is strong concordance for each clinical pattern within families.

Bulbar Palsy, Progressive↗
PubMed1991

Pelizaeus-Merzbacher disease: classical or connatal?

The clinical features and investigation results of 7 patients with Pelizaeus-Merzbacher disease (PMD) are described; one patient had a brain biopsy and two patients had an autopsy. This paper tries to differentiate the clinical features of the connatal and classical types of PMD. Transient stridor and nystagmus were early signs in both types of PMD. Our findings support the view that the more severe connatal form shows rapid neurological deterioration from an early age leading to death usually in the first decade. In younger patients in whom the evolution is still unclear, severe feeding problems and extrapyramidal features may suggest the connatal form. By contrast, in the classical form of PMD, cerebellar signs and cognitive deterioration are more prominent with a more slowly progressive course. Nuclear magnetic resonance imaging and brainstem auditory evoked potentials were very helpful in supporting the diagnosis of PMD either in a known affected family or in sporadic cases, but were not useful in distinguishing between the two types of PMD. Genetic counseling in this condition is difficult, particularly in the connatal form in which inheritance may be either X-linked or autosomal recessive.

Age Factors↗
PubMed1991

The distribution and functional properties of dendritic cells in patients with seronegative arthritis.

Dendritic cells (DC), potent antigen-presenting cells, are known to be increased in numbers in inflammatory lesions in rheumatoid arthritis and juvenile chronic arthritis. In this study, patients with seronegative arthritis were studied; the distribution and functional properties of DC enriched low density cells (LDC) from peripheral blood (PB) and synovial fluid (SF) were compared. The composition of LDC from both sources was similar, comprising approximately 30% DC, 60% monocytes with few T lymphocytes. SF was significantly enriched for LDC compared with paired peripheral blood (P less than 0.0001) or peripheral blood from healthy controls (P less than 0.001). In contrast, patient PB contained fewer LDC (P less than 0.05) overall than healthy controls. LDC from both sources were potent simulators of allogeneic PB T cells in a mixed leucocyte reaction (MLR), but in four out of 10 patients SF LDC were significantly more stimulatory. In autologous MLRs (AMLRs) SF T cells were not stimulated by either LDC population. This anergy of T cells was confined to the joint as patient PB T cells showed an AMLR response to PB LDC which was similar to that seen in cells from healthy controls. PB T cells also responded to SF LDC; in a minority of patients SF LDC caused significantly greater stimulation in AMLR than PB LDC and the possibility is discussed that this may represent presentation of antigen acquired in vivo.

Arthritis↗
PubMed1991

Peripheral blood and synovial fluid T cells differ in their response to alloantigens and recall antigens presented by dendritic cells.

Properties of T cells from inflammatory lesions were analysed by comparing the response of peripheral blood (PB) and synovial fluid (SF) T cells from 19 patients with a range of arthropathies to enriched allogeneic dendritic cells (DC) in a primary mixed leucocyte reaction (MLR). In 17 patients the proliferative response of SF T cells was significantly (P less than 0.05) less than that of PB lymphocytes. The reduced response of SF T cells was observed in all disease categories studied and could not be attributed to differences in cell number requirements or response kinetics. Addition of recombinant interleukin-2 enhanced the response of SF T cells in a dose-dependent manner. Cell mixing experiments suggested that active suppression was not the underlying mechanism of the poor MLR response of SF T cells. In contrast to the MLR response. SF T cells were able to mount vigorous proliferative responses to recall antigen presented by autologous antigen-presenting cells. The possibility is discussed that T cells compartmentalized at inflammatory lesions are a unique population with a diminished ability to interact with DC and respond to primary stimuli but an ability to respond to secondary antigenic challenge.

Arthritis↗
PubMed1991

Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions.

A patient with isolated cerebral Whipple's disease presented with signs of raised intracranial pressure and multiple ring enhancing intracerebral mass lesions evident on CT and MRI imaging. Characteristic intracellular bacilliform inclusions were identified in a brain biopsy. Clinical improvement followed treatment with parenteral antibiotics for two weeks and long term sulphamethoxazole-trimethoprim. As CNS relapse of Whipple's disease may occur after several years, long term treatment should include antibiotics that are able to cross the blood-brain barrier.

Adult↗
PubMed1990

Megalencephaly with dysmyelination, spasticity, ataxia, seizures and distinctive neurophysiological findings in two siblings.

A progressive neurological condition characterised by megalencephaly, spasticity, ataxia and seizures in two siblings of consanguineous parents is described. The electroencephalogram showed posterior discharges and an unusual photoparoxysmal response whereas brainstem auditory evoked potential findings were consistent with a white matter disorder. Computerized tomography scans revealed diffuse hypodensity of the white matter and a brain biopsy on one sibling showed features of dysmyelination without evidence of demyelination, Rosenthal fibres or the spongy changes characteristic of Canavan's disease. There was no detectable biochemical abnormality. This combination of clinical, neurophysiological and neuropathological abnormalities has not previously been described.

Biopsy↗
PubMed1989

Early onset Cockayne's syndrome: case reports with neuropathological and fibroblast studies.

Two patients with early onset Cockayne's syndrome are presented. In each case there was a striking failure of growth and developmental deterioration around six months of age. It has been suggested that early onset Cockayne's syndrome is a syndrome distinct from Cockayne's syndrome, but when the first patient died aged two years 10 months, examination of the brain showed a leucodystrohy with 'tigroid' demyelination similar to that reported in later onset cases of Cockayne's syndrome. Studies of the effects of UV irradiation on cultured fibroblasts from patients showed similar levels of inhibition of RNA synthesis to those seen in a control with Cockayne's syndrome. This evidence suggests it is appropriate to classify early onset Cockayne's syndrome with Cockayne's syndrome. Since there is a phenotypic overlap between early onset Cockayne's syndrome and COFS syndrome, they may both be classified within the same diagnostic group, but as yet no cellular studies with UV irradiation have been performed in COFS syndrome.

Brain↗
PubMed1989

Effect of temporary external stabilization on ventilator weaning after sternal resection.

The role of mechanical fixation of the chest wall in the treatment of flail chest remains controversial. We report a case of flail chest resulting from major sternal resection. The application of a temporary external stabilization device improved pulmonary mechanics by decreasing the respiratory rate from 36/min to 10/min while increasing tidal volume and vital capacity from 140 +/- 85 ml and 195 +/- 90 ml, respectively, to 450 +/- 110 ml and 905 +/- 310 ml, respectively. The improvement with the temporary device facilitated weaning from mechanical ventilation. We recommend consideration of this technique in selected cases of flail chest resulting from major chest wall resection.

Adult↗
PubMed1989

Overwhelming infection occurring in the immediate post-splenectomy period.

Overwhelming post-splenectomy infection (OPSI) is a serious condition associated with a high mortality rate. Occurring most often in the first two years after splenectomy, it has also been described up to 47 years after this operation. We report a further occurrence of this syndrome and stress the importance of early detection and aggressive treatment of this type of infection.

Hodgkin Disease↗
PubMed1989

Class II antigens on dendritic cells from the synovial fluids of patients with inflammatory arthritis.

Dendritic cells were enriched from synovial fluids (SF) of patients with inflammatory arthritis and studied by immunogold labelling and electron microscopy for expression of histocompatability antigens of the HLA-D locus. Dendritic cells from SF were larger than most of these from peripheral blood with a more extensive Golgi region and more lysosomes and microfilaments. Class II histocompatability antigens HLA-DR, -DP, -DQ and that labelled by the antibody RFDI were abundant on the dendritic cells. The macrophages in the enriched cells showed labelling for DR but little labelling with the other antibodies. DR, DP and RFDI were often concentrated at areas of contact between dendritic and other cells (other dendritic cells, macrophages or lymphocytes). On incubating labelled cells at 37 degrees C for 30 min many macrophages lost their DR label but dendritic cells always retained some surface label. Some gold labelling DR and DP was found in characteristic channels between the veils and became internalized in membrane-bound structures. A small proportion of the RFDI label internalized in areas resembling coated pits. Less DQ label internalized and appeared on vesicles inside vacuoles. Material bound to different class II molecules may thus be internalized or processed differently by dendritic cells. The presence in inflammatory lesions of large activated dendritic cells with high expression of class II antigens suggests that these cells could be presenting antigen to lymphocytes within the joints.

Arthritis↗
PubMed1988

Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease.

A report of cell loss in the nucleus basalis of Meynert in patients with Wernicke-Korsakoff disease prompted the examination of thiamine pyrophosphate (TPP)-dependent enzymes in the brain and peripheral tissues of patients with Alzheimer's disease. In these brains, the activities of the 2-ketoglutarate dehydrogenase complex were reduced more than 75% and those of transketolase more than 45%. Decreases occurred in histologically damaged and in relatively undamaged areas. Small but statistically significant abnormalities of transketolase, but not of 2-ketoglutarate dehydrogenase complex, were identified in red blood cells and cultured fibroblasts. Previous studies have shown deficiencies in the brain and variable effects in peripheral tissues on another TPP-dependent enzyme--the pyruvate dehydrogenase complex. Activities of TPP-dependent enzymes appear to be deficient in the brain and perhaps in some peripheral tissues in patients with Alzheimer's disease.

Aged↗
PubMed1988

Congenital varicella-zoster. A serologically proven case with necrotizing encephalitis and malformation.

Following maternal chicken pox in the 14th week of pregnancy, a male infant was born with low birth weight, muscle wasting and limb contractures, hypotonia and areflexia. A rising titre of varicella-zoster-specific IgM (by enzyme-linked immunoabsorbent assay) confirmed congenital infection, and electromyogram showed widespread denervation. Death occurred at 8 days. Neuropathological examination revealed destructive and inflammatory lesions of cerebral cortex and white matter, thalamus, brain stem and spinal cord. In addition there were cerebellar heterotopias and bilateral polymicrogryic malformations of the insular cortex.

Central Nervous System↗
PubMed1988

Differences between the histology of normal spleen and that of regenerated ectopically implanted splenic tissue.

The histology of regenerated ectopically implanted spleen (splenotic tissue) from splenectomized rats was compared with that of normal rat spleen. Computer-assisted morphometric analysis revealed significant decreases in both the number and area of splenic nodules in splenotic tissue when compared with normal spleen. It is suggested that the reduction in the amount of white pulp present could explain at least in part the reduced ability of splenotic tissue to deal with infection.

Abdominal Neoplasms↗
PubMed1988

Detection of splenosis: 99Tcm tin colloid scanning and computed transmission tomography compared.

Ten patients who had been splenectomized for trauma between 1 and 11 years previously were studied by computed tomography (CT) and radionuclide scanning with 99Tcm tin colloid on the same day. Computed tomography detected splenic tissue in three patients. Radionuclide scanning detected splenic tissue in eight patients, including two cases of typical splenosis not identified by CT. Radionuclide scanning was found to be more sensitive in the detection of residual splenic tissue than CT.

Adult↗