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Biomedical subjects

B Harding

Publications and source records attributed to B Harding.

17 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↗
PubMed1979

Outcome of anorexia nervosa.

100 females with anorexia nervosa were followed up 4-8 years after first presentation. All but 12 had had refeeding and/or psychotherapy. 48 had a good outcome (weight at least near normal, regular menstruation, largely satisfactory mental state and psychosexual and psychosocial adjustments) but outcome was intermediate in 30, and poor in 20 patients. 2 had died. Poor outcome could be positively associated with clinical data such as longer duration of illness, older age of onset and presentation, lower weight during illness and at presentation, presence of symptoms such as bulimia, vomiting, and anxiety when eating with others, poor childhood social adjustment, and poor parental relationships.

Adaptation, Physiological↗
PubMed1978

Selective decrease in antibody-dependent cell-mediated cytotoxicity in systemic lupus erythematosus and progressive systemic sclerosis.

With the use of two target cells (chicken erythrocytes and Chang cells), the antibody-dependent cell-mediated cytotoxicity (ADCMC) of peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) was studied. Patients with active SLE had a significant reduction in ADCMC against Chang cells whereas cytotoxicity against chicken erythrocytes did not differ significantly from that of a control population. Similarly, a group of PSS patients with positive anti-DNP antibodies demonstrated a selective reduction in ADCMC against Chang cells. These findings support the concept that different effector cells mediate ADCMC against chicken erythrocytes and Chang cells, and indicate that in some patients with SLE and PSS there is a selective reduction or blockade of the ADCMC effector cell active against Chang cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Effects of varying the interval between courses of methotrexate on its myelotoxic and anti-leukaemic activities.

The toxicity produced by two courses of methotrexate separated by different intervals has been studied in matched groups of rats. The maximum degree of neutropenia reached when courses were separated by 8 days or more was no greater than that seen after a single course of methotrexate. However, when courses of neutropenia following the second course of methotrexate was directly related to the level of depression of bone marrow cell numbers at the time of the second course. Conversely the anti-leukaemic effects of 2 courses of methotrexate, in terms of time of onset of leukaemia and time of death in rats transplanted with a syngeneic T-cell leukaemia, are shown to be similar when courses of methotrexate are separated by between 2 and 12 days. Thus in this system, chemotherapeutic schedules using methotrexate may be designed on the basis of minimal host toxicity without prejudicing anti-leukaemic effects. These results are discussed in relation to toxicity and anti-leukaemic effects observed during UKALL trials of treatment in acute lymphoblastic leukaemia.

Animals↗
PubMed1977

Myelotoxicity of methotrexate in animals with pyogenic infection.

Rats stimulated into prolonged increased neutrophil production by the induction of a unilateral pyo-hydronephrosis showed consistent profound neutropenia when methotrexate (MTX) was given during the first 2 d of infection. Thereafter greater neutropenia than that observed in non-infected rats was only observed in occasional animals. There was a significant correlation between the degree of neutropenia induced by MTX and the day after MTX upon which this occurred. The main target for myelotoxicity by MTX appears to be the myelocyte. Its precursors seem relatively insensitive.

Agranulocytosis↗
PubMed1976

In vitro activity of anti-DNA antibodies from SLE patients in antibody-dependent cell-mediated cytotoxicity.

Peripheral blood lymphoid cells from normal individuals were cytotoxic to target cells coated with DNA when incubated with serum from patients with systemic lupus erythematosus (SLE) but not when incubated with serum from normal subjects. Sera from SLE patients with clinically acitve disease were more active than sera obtained from those patients in remission. In the absence of normal lymphocytes, SLE sera were not cytotoxic to the DNA-coated cells. The active fraction in the serum appeared to be IgG anti-DNA antibodies. These studies indicate that anti-DNA can operate through the antibody-dependent cell-mediated cytotoxicity mechanisms in vitro.

Antibodies↗
PubMed1976

Immunologic responses in patients with lepromatous leprosy.

Immunologic responses were measured in 46 patients with lepromatous leprosy. These patients were not distinguishable from controls on the basis of responses to soluble intradermal antigens, sensitization to contactants, peripheral blood T- and B-cell percentages, in vitro lymphocyte responses to a mitogen, or the prevalence of autoantibodies. Generalized immunologic abnormalities in patients with lepromatous leprosy are neither predisposing causes nor necessary accompaniments of lepromatous leprosy, but are probably remote sequellae of the illness. By implication, the generalized immunologic abnormalities reported in other diseases are likely to be remote sequellae of the particular illness.

Adult↗
PubMed1975

Reduced antibody-dependent cell-mediated cytotoxicity in systemic lupus erythematosus.

The peripheral blood mononuclear cells from twenty-three patients with SLE were studied. They showed a reduction in antibody-dependent cell-mediated cytotoxicity. This reduction was significantly related to disease activity. No correlations were found with other clinical features. Some of the possible explanations for this finding are discussed.

Adult↗