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Biomedical subjects

D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 433 records · Page 24Linked to original sources

The use of C3d as a means of monitoring clinical activity in systemic lupus erythematosus and rheumatoid arthritis.

Plasma samples from 44 patients with systemic lupus erythematosus (SLE) and 43 with rheumatoid arthritis (RA) were assayed for C3d, a breakdown product of the third component of complement (C3), which was also measured in parallel. Levels of C3d varied in direct proportion with disease activity in RA, whereas C3 showed little change. Although C3d values also increased with worsening clinical condition in SLE, this trend was not considered to be sufficiently clear to be useful and did not provide any advantage over the routinely performed C3 assay.

Arthritis, Rheumatoid↗

Monoclonal antibodies to human leucocyte antigens in polymyositis and muscular dystrophy.

Biopsy specimens from patients with treated or untreated polymyositis and muscular dystrophy controls were examined by indirect immunoperoxidase staining with a panel of monoclonal antibodies to human leucocyte antigens. In untreated polymyositis, helper/inducer T cells were the predominant T cell subset. In treated cases few T cells were seen. Overall, few T cells were seen in dystrophic cases, most infiltrating cells being dendritic and lacking T cell antigens. Staining of sarcolemma with anti-HLA class 1 antibody is weak or negative except in areas adjacent to infiltrating leucocytes or where muscle fibre damage is apparent.

Adult↗

Immunoglobulin deposition in skeletal muscle in primary muscle diseases.

Using direct immunofluorescence the deposition of IgG, IgM, IgA, Clq and C3 was studied on muscle biopsies from 39 patients with polymyositis/dermatomyositis, 21 patients with muscular dystrophy, 57 other disease controls and 10 healthy volunteers. Three staining patterns were observed, sarcolemma/basement membrane blood vessel wall and intrafibrous. Sarcolemma/basement membrane staining, but not blood vessel wall or intrafibrous staining, occurred more frequently (p less than 0.05) in the polymyositis/dermatomyositis group compared with the two other disease groups. Immunoglobulin deposition was useful in distinguishing myopathic from neuropathic disorders. Grouping the patients into those with connective tissue diseases and those without, sarcolemma/basement membrane and blood vessel wall staining were shown to distinguish the two groups (p less than 0.05). An analysis of the histological abnormalities in the polymyositis/dermatomyositis group was performed and related to immunoglobulin/complement deposition. Fibre damage, rather than the presence of a mononuclear perivascular infiltrate, was shown to be the best correlate with each of the three staining patterns. Immunoglobulin and/or complement deposition in skeletal muscle is an abnormal finding and the results described support the notion that humoral abnormalities may be detected frequently in polymyositis/dermatomyositis. In addition, the inability to distinguish polymyositis/dermatomyositis from muscular dystrophy limits the potential value of direct immunofluorescence as a diagnostic tool.

Adult↗

Predictive value of SS-B precipitating antibodies in Sjoögren's syndrome.

As part of a screening programme several patients were identified with antibodies to the nuclear antigen SS-B. Fifteen were examined and 11 found to have Sjögren's syndrome, though this had not been suspected by most of the referring physicians. In contrast, among a group of 17 patients with overt Sjögren's syndrome, most of whom also had rheumatoid arthritis, only one had antibodies to SS-B. Patients presenting with polyarthralgia found to be SS-B positive may be likely to develop Sjögren's syndrome but unlikely to develop rheumatoid arthritis. The detection of SS-B antibodies may antedate clinical evidence of Sjögren's syndrome by months or even years. These results emphasise the clinical heterogeneity of Sjögren's syndrome.

Adult↗

Erosive rheumatoid arthritis co-existing with systemic lupus erythematosus. A report of a case, also showing atlanto-axial subluxation.

A 28-year old female is described with a 12-year history of seropositive, erosive rheumatoid arthritis. Subsequently, she developed systemic lupus erythematosus diagnosed both serologically and on renal biopsy. As has previously been emphasised, these two diseases occur rarely in the same patient. HLA typing revealed the patient was HLA - B8 positive and that she had inherited this genetic marker from her mother who is Irish, rather than from her West Indian father. The patient has developed marked atlanto-axial subluxation, a feature not noted in six patients previously described as having both diseases.

Adult↗

A study of vascular permeability in normal skeletal muscle and inflammatory myopathies using a fluorescein dye technique with percutaneous needle biopsy.

Percutaneous needle biopsy of the vastus lateralis muscle was performed immediately prior to the intravenous injection of 5 ml of 20% fluorescein sodium, in 2 control subjects and 2 patients with polymyositis. Repeat biopsies were performed 5, 10 and 15 minutes after injection. Similar biopsies were taken prior to, and 10 minutes after, fluorescein injection in 1 control subject and 15 patients with a variety of inflammatory muscle conditions including polymyositis, some of whom were on treatment with corticosteroids. Apart from one patient, with polymyalgia rheumatica, increased penetration of dye was found only in those patients with polymyositis, particularly around areas of cellular infiltration, necrosis and phagocytosis and in the periphery of muscle fibres. Corticosteroid therapy appeared to reduce the amount of dye permeating muscle tissue in patients with polymyositis. It is suggested that reducing the abnormally increased vascular permeability in damaged muscle from patients with polymyositis may represent one mode of action of corticosteroids in this condition, and that the amount of fluorescein permeating muscle may be helpful in the diagnosis where conventional clinical and histological criteria are not conclusive.

Biopsy, Needle↗

A study of migraine in systemic lupus erythematosus.

An increased prevalence of classical migraine was found in 30 female patients with systemic lupus erythematosus (SLE) compared with an age and sex-matched control group by means of a detailed questionnaire. No significant difference were found between the patients and controls, who had classical and common migraine or visual auras without headache, with regard to a family history of migraine, the age of onset of the migraine, Raynaud's phenomenon, or use of oral contraceptives. Increased activity of the lupus was not generally associated with an increase in migraine attacks. It is suggested that migrainous phenomena may be a feature of SLE.

Adolescent↗

Neutrophil function in systemic lupus erythematosus and other collagen diseases.

Using a whole blood technique we assessed neutrophil migration, phagocytosis, and killing in a group of 20 patients with systemic lupus erythematosus (SLE) and in 8 patients with other connective tissue disorders. In the untreated cases of SLE neutrophil migration was significantly depressed, but it was usually normal in the treated group. This may be attributable either to an intrinsic neutrophil abnormality or to a humoral factor. Although isolated abnormalities of phagocytosis and killing were observed in SLE, these functions were normal when the patients were considered as a group. The treated patients with other collagen diseases showed enhanced migration in both autologous and control plasma, normal phagocytosis, and enhanced killing in autologous plasma only. The small group of untreated, non-SLE patients showed some depression of all 3 functions. There was no correlation between neutrophil function and clinical activity of disease. In the SLE patients there was no correlation between neutrophil function and circulating immune complexes.

Blood Bactericidal Activity↗

Methyl prednisolone pulse therapy in the treatment of systemic lupus erythematosus.

Twenty patients with active systemic lupus erythematosus (SLE) were treated with methyl prednisolone pulse therapy (MPPT) and followed up for up to 24 weeks (mean 18 weeks). Beneficial effects of MPPT were observed principally on arthralgia, pleuritic pain, vasculitic skin rash, pyrexia, and lymphadenopathy. The serological tests showing the most improvement were ds DNA binding and the serum C3 level. MPPT was found to be both safe and easy to administer. It may be of value in treating patients with SLE whose disease is not controlled by moderate doses of corticosteroids and may also enable the dose of maintenance corticosteroids to be reduced appreciably.

Female↗

Studies on autoantibodies to poly (adenosine diphosphate-ribose) in SLE and other autoimmune diseases.

Sera from 41 patients with systemic lupus erythematosus (SLE), 87 controls with various diseases, and 30 normal subjects were examined for poly (adenosine diphosphate-ribose) and ds DNA binding. Elevated levels of poly (ADP-ribose) binding were found in 73% of the SLE patients compared with 58% who had raised ds DNA binding. In a further study of 160 sera from 27 patients with SLE, levels of antipoly (ADP-ribose) antibodies were shown to correlate with clinical activity better than either anti-ds DNA or ss DNA antibodies.

Adult↗

Haematological aspects of systemic lupus erythematosus: a reappraisal using automated methods.

Twenty-two haematological parameters were measured in 30 patients with systemic lupus erythematosus (SLE) at 110 patient attendances. Using a 10,000 cells per sample automated differential counter, the major abnormalities demonstrated were: lymphopenia, monocytopenia, eosinophilopenia (each of which showed strong correlation with steroid therapy) and increased numbers of cells of high peroxidase activity. Despite the common lymphocytopenia elevation of large unstained cells was noted in 20% of patients. However, no patient with severe disease had a lymphocyte count above 1.9 X 10(9)/l or a haemoglobin above 11.7 g/dl.

Basophils↗

Useful laboratory measurements in the management of systemic lupus erythematosus.

Thirty-five patients with systemic lupus erythematosus (SLE) have been monitored clinically and serologically for up to three and a half years. The data collected was analysed by computer using the Statistical Package for the Social Sciences Program. The patients were categorized into severely active, moderately active and inactive disease groups and associations between clinical state and laboratory tests were sought. No single test was found to distinguish, reliably, the clinical groups but levels of circulating immune complexes (by polyethylene glycol precipitation), platelet count and ESR were shown to distinguish inactive from active disease (p less than 0.05). Severely active disease was distinguished from the less active forms by circulating immune complex levels (Clq solid phase assay) double-stranded DNA binding, lymphocyte count, and CH50 estimations (p less than 0.05). Tests were found to differ considerably in their ability to reflect disease activity when patients were separated into sub-groups according to the major clinical features (eg. arthralgia, renal disease and vasculitic rash). However, those patients with cerebral manifestations and thrombocytopenia proved to be the most difficult to assess. Discriminant function analysis showed that a maximum of 44 per cent of cases could be correctly classified into their clinical grades when combinations of four out of five laboratory tests were used. These results emphasise the continuing need for better tests to monitor the course of SLE.

Adolescent↗

The adult presenting idiopathic Fanconi syndrome.

The adult presenting Fanconi syndrome is a rare familial disorder. A 30-year follow-up of one of the original families in the literature is reported here. Two important points have emerged. Firstly, the inheritance in this family is dominant, not recessive as originally suggested, and there remains no good example in the literature of a recessive inheritance of this disorder. Second, in this family lactic aciduria and tubular proteinuria are probably the earliest manifestations of the disorder in childhood, with glycosuria and aminoaciduria developing in the second decade and osteomalacia from the start of the fourth decade. Glomerular function deteriorates slowly but is compatible with a normal lifespan.

Adult↗

Cyclosporin A for the treatment of systemic lupus erythematosus.

Cyclosporin A (CyA) was given to five patients with active systemic lupus erythematosus (SLE) at a dose of 10 mg/kg/day orally. No patient was able to take the drug for longer than seven weeks because of side effects including nephrotoxicity. Angio-oedema was noted in three patients and serum C1 esterase inhibitor levels were shown to be depressed in four out of five patients whilst taking CyA. Two patients did experience an improvement in their arthralgia but given the side effects induced we cannot, at present, recommend CyA for the treatment of SLE.

Adult↗

Variation in circulating immune complex levels with diet, exercise, and sleep: a comparison between normal controls and patients with systemic lupus erythematosus.

Circulating immune complexes (CIC) were measured in 4 normal controls and 8 patients with systemic lupus erythematosus (SLE) by a polyethylene glycol precipitation (PEG) method during a 24-hour period. In all the normal controls levels fell during sleep and after drinking 1 pint (568 ml) of milk and rose before getting out of bed and after moderate exercise. There were also marked differences in the patterns of rise and fall of the CIC levels between the normal controls and patients with SLE. Insufficient account has been taken of these physiological influences in CIC levels in previous studies attempting to relate disease activity to quantitative levels.

Adult↗

Familial late onset oculopharyngeal muscular dystrophy.

An English family is described several members of which have suffered from oculopharyngeal muscular dystrophy. No symptoms were noticed in any affected members of the family until aged at least 50 years. An autosomal dominant pattern of inheritance is clearly shown.

Age Factors↗