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Biomedical subjects

D N Mitchell

Publications and source records attributed to D N Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1986

Oro-facial granulomatosis. Response to elemental diet and provocation by food additives.

We report the case of an 8.5-year-old girl with oro-facial granulomatosis associated with clinical atopy, in whom relapse of her granulomatous disorder was shown to be related to exposure to specific food additives, viz. carmoisine, sunset yellow and monosodium glutamate. Treatment with a restricted diet resulted in considerable regression in the facial swelling which has been maintained for 6 months. A brief account of the histological features, both under light and electron microscopy, is given, together with a description of the use of nuclear magnetic resonance scanning in the assessment of this disease. The patient had no evidence to support a diagnosis of sarcoidosis or Crohn's disease.

Child↗
PubMed1986

Early cellular responses to intradermal injection of Kveim suspension in normal subjects and those with sarcoidosis.

In a detailed controlled study of the cellular response to Kveim suspension in vivo we used immunohistological and histochemical methods to examine cryostat sections of immature Kveim biopsy specimens in subjects with sarcoidosis and normal controls. Changes seen at 48 hours, at which time papular reactions have sometimes been reported, are described. Eight cases of sarcoidosis previously confirmed by a positive Kveim test were studied, in five of whom the test remained positive; plus two subjects with sarcoidosis studied prospectively; and four healthy controls. There were two main features of the 48 hour response: collagen disruption with associated histiocytes, which showed increased acid phosphatase activity; and perivascular infiltrates of lymphocytes and small groups of dendritic cells. The T4:T8 ratios in the infiltrates were similar to those found in the peripheral blood of the subjects, and few lymphocytes showed evidence of activation. T lymphocytes were also seen free in the dermis and migrating to the epidermis. Small juxtacapillary clumps of dendritic cells, identified by NA1/34 (= OKT6; Langerhans' cells) and RFD1 (interdigitating cell) monoclonal antibodies, were found. The Langerhans' cells in the epidermis were, however, normal in number and distribution. These features, which were found in all groups, are not consistent with pre-existing hypersensitivity to Kveim suspension in sarcoidosis. Subsequent differences between sarcoid and normal subjects in the development of granulomas in the Kveim response may therefore relate to the different handling of the foreign material by the cells affected, rather than to differences in the early non-specific recruitment of the cells to the test site.

Adult↗
PubMed1985

Oro-facial granulomatosis--a clinical and pathological analysis.

A study of 60 patients with oro-facial granulomatosis has been conducted and the clinical presentation of this disorder defined. It encompasses the previously recognised clinical entities of Melkersson-Rosenthal syndrome and cheilitis granulomatosa. The pathological features of the disease are lymphoedema and the presence of multiple non-caseating giant cell granulomata. These granulomata are histologically indistinguishable from those found in both gastrointestinal Crohn's disease and systemic sarcoidosis. Within this series of patients, nine had evidence suggestive of gastrointestinal Crohn's disease, and in six this was confirmed. A diagnosis of sarcoidosis was made in a further two patients. The relationship of oro-facial granulomatosis to these systemic granulomatous diseases is not yet clear. Patients with oro-facial granulomatosis who have gastrointestinal symptoms should be investigated for the presence of gastrointestinal Crohn's disease. Those without symptoms should be investigated for evidence of malabsorption or serological evidence of Crohn's disease. Within the present study, the erythrocyte sedimentation rate, full blood count, corrected whole blood folate, serum albumin and calcium were the most sensitive markers of gastrointestinal involvement. Sarcoidosis should be considered in all patients with oro-facial granulomatosis. The absence of clinical signs suggestive of sarcoidosis, a normal chest radiograph and normal levels of serum angiotensin-converting enzyme makes sarcoidosis unlikely.

Adolescent↗
PubMed1984

Serum angiotensin-converting enzyme and delayed hypersensitivity in pulmonary tuberculosis.

In contrast to sarcoidosis, there was no difference between serum angiotensin-converting enzyme (ACE) levels in a group of 100 adult Indonesian patients with active pulmonary tuberculosis and in 108 matched healthy control subjects. There was a significant inverse correlation between the diameter of the cutaneous reaction to tuberculin and serum ACE levels. It is postulated that, as both delayed hypersensitivity and ACE synthesis within granulomas appear to be the result of T-cell induced secretory activities of macrophages, this inverse relationship results from competition for receptor sites for the relevant signal molecules on the macrophage surface.

Adolescent↗
PubMed1984

Evidence for the persistence of paramyxoviruses in human bone marrows.

Human bone marrow cells derived from multiple sclerosis (MS) and control patients were screened for a number of virus antigens by the fluorescent antibody technique using monoclonal antibodies. The results showed that antigens of the paramyxovirus, simian virus 5, were present in about 60% of MS and 25% of control bone marrows. About 25% of the MS and 50% of control bone marrows were found to contain nucleoprotein antigen of the human parainfluenza types 1 and 3. These experiments demonstrated that paramyxoviruses can persist in human tissues possibly in a defective or repressed state.

Animals↗
PubMed1984

Does simian virus 5 infect humans?

Simian virus 5 (SV5) isolates derived after co-cultivation of human bone marrow aspirates of multiple sclerosis (MS) patients were shown by immunoprecipitation, cross-neutralization and haemagglutination inhibition techniques to be similar antigenically but not identical to the prototype strain. Analyses of human sera (MS and control) showed that about 20% contained neutralizing antibodies to SV5 and immunoprecipitated the specific SV5 HN polypeptide. A competition assay using a specific SV5 monoclonal antibody confirmed that a human serum containing such neutralizing activity also blocked a specific SV5 epitope whereas another human serum with demonstrable antibodies to the related human parainfluenza virus type 2 did not block this epitope. These tests therefore suggested that SV5 can infect humans. However, there was no indication, on the basis of these tests, of any aetiological relationship of the SV5 infection to the induction of MS.

Antibodies, Viral↗
PubMed1983

Variation in immunoglobulin levels and circulating immune complexes in sarcoidosis. Correlation with extent of disease and duration of symptoms.

Sixty-three patients with clinically definite sarcoidosis confirmed histologically and/or by a positive Kveim test were studied according to the clinical and radiographic extent and known duration of their disease and symptoms. Immunoglobulin levels were not raised among patients with bilateral hilar lymphadenopathy (BHL) alone, but IgG and IgA were raised among patients with pulmonary sarcoidosis, most markedly among patients with long-standing active disease. Serum IgM was found elevated in extrathoracic sarcoidosis. West Indian males had the highest levels of IgG. The presence of circulating immune complexes reacting with conglutinin was strongly associated with a recent symptomatic onset of sarcoidosis; they were more prevalent in patients with BHL and erythema nodosum. In contrast, polyethylene glycol precipitable immunoglobulins were associated with long-standing active disease and with neurologic involvement.

Adult↗
PubMed1981

Association of HLA B8 with spontaneous resolution in sarcoidosis.

HLA may influence the natural history of some diseases. HLA frequencies have been compared in 164 healthy control subjects, 50 patients with sarcoid lung fibrosis, and 37 patients with sarcoidosis that resolved spontaneously. B8 was increased significantly in the resolved group compared to both healthy control subjects (p less than 0.001) and the fibrotic group (p less than 0.01). The results support the findings of other investigators, and are consistent with the hypothesis that inherited host factors, perhaps related to immune response, influence the clinical expression of sarcoidosis.

Adult↗
PubMed1980

Transbronchial lung biopsy through fibreoptic bronchoscope in diagnosis of sarcoidosis.

Sarcoidosis was ultimately diagnosed in a consecutive series of 79 patients, of whom 24 presented with unusual features. Histological support for this diagnosis was obtained in 37 out of 42 patients who underwent transbronchial biopsy; epithelioid and giant-cell granulomas were also found on biopsy of the bronchial mucosa in 17 out of 22 patients. Kveim tests were completed in 44 patients: results were positive in 19, equivocal in 11, and negative in 14. In 16 patients histological support was obtained on biopsy of various other tissues. The clinical presentation of the disease and the degree of histological support provided by the various procedures used in reaching a diagnosis of sarcoidosis varied considerably. Transbronchial biopsy of the lung is a useful advance in diagnosing sarcoidosis and provided a higher diagnostic yield than any other method.

Biopsy↗
PubMed1979

Mediastinal lymph node biopsy in sarcoidosis.

Mediastinoscopy, in the skilled hands of a thoracic surgeon has proved to be a safe, cosmetically accepted procedure with negligible complications. It has yielded a high rate of diagnostic lymph node tissue; overall greater than 82% among patients with sarcoidosis, including patients presenting with pulmonary mottling only or with a normal chest radiograph. Among patients with lymphatic tuberculosis it enabled the isolation of human M. tuberculosis following culture of the lymph node removed on Löwenstein-Jensen medium in greater than 79% of cases. A precise histological diagnosis was obtained in all 14 patients presenting with hilar and/or paratracheal lymphadenopathy attributable to malignant disease.

Adult↗
PubMed1979

Splenomegaly and splenectomy in sarcoidosis.

The natural history of 30 patients with sarcoidosis who showed histological evidence of granulomatous involvement of the spleen has been studied; 24 patients had splenomegaly, 16 of whom had splenectomy. The main indication for splenectomy was splenomegaly and resultant discomfort. Corticosteroids reduced spleen size but reduction or withdrawal of the relatively high dosage required resulted in rebound splenomegaly within a period of three months to three years. Haematological abnormalities were controlled by splenectomy in all patients so affected, but the natural history of their sarcoidosis remained unaltered.

Adolescent↗
PubMed1978

Isolation of an infectious agent from bone-marrows of patients with multiple sclerosis.

Bone-marrow aspirates from 5 patients with recent episodes of multiple sclerosis (M.S.) contained increased numbers of plasma cells, and aspirates from 3 of these patients contained atypical reticulum cells. When bone-marrow from 4 of the patients was inoculated into cell cultures a cytopathic effect (C.P.E.) was observed, and this effect could be serially passaged to further cultures. The C.P.E. was not observed when ether-treated extracts of cells showing C.P.E. were used for passage or when the passage material was filtered through a 100 nm filter. Appearance of C.P.E. was delayed in cultures inoculated with 220 nm filtrates of inoculum was passed through filters of greater pore size. No C.P.E. was observed after culture of bone-marrow aspirated from each of 7 patients under clinical investigation for disorders other than M.S.

Adult↗
PubMed1978

Induction of granulomas in mice by Crohn's disease tissue.

Normal and immunodeficient CBA and A2G strain mice were inoculated with crude (100 to 20 to 30 micrometer), cell-free (0.2 micrometer) filtrates of Crohn's or noninflammatory bowel disease tissue homogenates, which were either fresh or frozen to -70 degree C. Mice of each strain developed epithelioid and giant cell granulomas both locally at the site of injection and systemically in response to crude and cell-free filtrates of Crohn's tissues. Control mice did not develop such changes. The granulomas evolved slowly, predominantly between 9 and 27 months. The granuloma-inciting agent has been shown to be present in ileum, colon, and mesenteric lymph nodes of patients with Crohn's disease and it withstands freezing to -70 degree C. The use of Crohn's tissues common to this study and one in rabbits previously reported, suggests that the induction of granulomas by this agent is not strain- or species-specific, and is independent of the immune status of CBA mice.

Animals↗