Search PubMed⌕ Search

Biomedical subjects

D N Mitchell

Publications and source records attributed to D N Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1977

Sarcoidosis: histopathological definition and clinical diagnosis.

Sarcoidosis is best defined in histopathological terms as 'a disease characterised by the presence in all of several affected organs and tissues of non-caseating epithelioid-cell granulomas, proceeding either to resolution or to conversion into hyaline connective tissue'. Although the defining characteristics are thus histopathological, diagnosis during life depends largely upon clinical, radiological, and immunological findings. The amount of support required from histology varies greatly from case to case. Though histology from one site cannot in itself establish the diagnosis of sarcoidosis, a generalised disease, detailed histological study of biopsy tissue makes an important and often essential contribution. In many instances, complete lack of necrosis, an intact reticulin pattern, and failure to demonstrate infective agents permit an unequivocal statement of compatibility with this diagnosis; however, a compatible clinical picture and absence of evidence of known causes of local granulomatous reactions or of other generalised granulomatous diseases are required for definitive diagnosis. In some, the histological pattern deviates in some particular from the accepted 'typical' pattern; there may be a little necrosis, the follicular pattern of the granuloma may be less than perfect, and exclusion of known infective agents can never be absolute. In such instances, subsequent surveillance, including possible response to treatment, may show a clinical course justifying a diagnosis of sarcoidosis, and necropsy may establish it; but it must be recognised that in a few cases, particularly those in which the clinical evidence of disease is confined to one organ, diagnosis is likely to remain in doubt for long periods. Reports on the histology of the Kveim test should be made without knowledge of clinical findings and in terms of the presence and quality of granulomatous response. A granulomatous reaction to a validated test suspension makes a contribution to diagnosis similar to the finding of granulomas in an additional organ or tissue.

Adult↗
PubMed1976

Transmissible agents from human sarcoid and Crohn's disease tissues.

Mice were inoculated with human sarcoid tissue homogenates or with a first or a second passage homogenate of mouse tissue (including 0.2 mum membrane filtrates) originating from the inoculation of human sarcoid, Crohn's disease, or control tissue homogenates. Epithelioid and giant cell granulomas were present in the footpads and/or viscera of some of the mice given homogenates originating from each sarcoid or Crohn's disease tissue 15 months after inoculation but were not present in mice given control homogenates. Among mice given homogenates originating from human sarcoidosis, granulomas were present in many organs and tissues; in contrast, a pattern of selective dissemination of visceral granulomas was found among mice given homogenates originating from Crohn's disease. This differential distribution of visceral granulomas also followed the inoculation of 0.2 mum membrane filtrates. Granulomatous responses at Kveim test sites in the ear 9-17 months after inoculation of homogenatesoriginating from human sarcoidosis or Crohn's disease were confined to mice showing granulomas in footpads of viscera. The ability of the transmissible agents to induce granulomas in mice was destroyed when sarcoid or Crohn's tissues were autoclaved or when sarcoid homogenates were stored at -20degreesC for 1 week or exposed to 60Co irradiation (2.5 MR).

Animals↗
PubMed1976

Evidence of an agent transmissible from ulcerative colitis tissue.

Five New Zealand White rabbits were injected intracolonically with homogenates (100 mum) of ulcerative-colitis tissue. Histological changes closely similar to those seen in the human donors were present in the mucosa and submucosa of the large intestine of four of these rabbits 3-12 months later. Similar changes were seen in the large intestine of three of four rabbits 6-13 months after intravenous or intracolonic inoculation of homogenates of rabbit mesenteric lymph-nodes after passage of human ulcerative colitis tissue (100 mum or 0.2 mum). Three of thirty A2G strain mice injected with similar tissue homogenates (100 mum or 0.2 mum) from patients with ulcerative colitis into the footpad or intraperitoneally, had granulomatous changes in footpad, bowel, liver and/or spleen 3-22 months later. Such changes did not develop in rabbits or mice inoculated with tissue from normal controls. The results of these experiments suggest that a transmissible factor is involved in the aetiology of ulcerative colitis.

Animals↗
PubMed1976

The nature and physical characteristics of a transmissible agent from human sarcoid tissue.

In controlled experiments normal and immunologically deficient CBA mice were inoculated in footpads, intraperitoneally, or intravenously with whole fresh, fresh supernatant, and fresh filtered supernatant (0.2 mu) or with each of these homogenates after autoclaving or their further exposure to 60Co irradiation (2.5 MR). As controls, mice were inoculated with identically prepared fresh nonsarcoid homogenates by these same routes. Epithelioid- and giant-cell granulomas were present in viscera of mice given each fresh sarcoid homogenate by any of these routes 15 months after inoculation, but were not present in mice given nonsarcoid autoclaved sarcoid, or 60Co-irradiated sarcoid homogenate. Successful passages were achieved following the inoculation of whole or filtered supernatant (0.2 mu) sarcoid mouse tissue homogenate into footpads, intraperitoneally, or intravenously. The epithelioid- and giant-cell granulomas evolved slowly over a period of many months following the inoculation of sarcoid tissue or passage homogenates and persisted thereafter in association with Kveim reactivity. The transmissible agent is inactivated when homogenate prepared from human sarcoid or mouse sarcoid tissue is autoclaved or 60Co-irradiated, can be repeatedly passaged, and has been shown to pass an 0.2-mu membrane filter. It is therefore presumably viable and must approximate to the size of a virus or be capable of being deformed so as to pass a filter of such a pore size (0.2mu), L forms.

Animals↗
PubMed1976

Further observations on the transmissibility of Crohn's disease.

In controlled experiments normal and immunologically deficient CBA mice were inoculated with whole fresh, fresh autoclaved, fresh supernatant, or filtered supernatant (0.2 mu) of whole Crohn's or non-Crohn's homogenate into footpads, intraperitoneally or intravenously. Epithelioid and giant-cell granulomas were present in a substantial proportion the footpads and in bowel or mesenteric lymph nodes of a proportion of given each fresh Crohn's homogenate by any of these routes 15-17 months after inoculation, but were not present in mice given non-Crohn's or autoclaved Crohn's homogenate. Successful passages were achieved following the inoculation of Crohn's mouse tissue homogenates, including passage from mice receiving filtered supernatant (0.2mu) or whole Crohn's homogenate, into footpads or intravenously. The epithelioid- and giant-cell granulomas evolved slowly over a period of many months following the inoculation of Crohn's tissue or passage homogenates and persisted thereafter. The transmissible agent is inactivated when homogenate from Crohn's tissue is autoclaved, can be passaged successfully into footpads or intravenously, and has been shown to pass an 0.2 mu membrane filter. It is therefore presumably viable and must approximate to the size of a virus or be capable of being deformed to pass a filter of such a pore size (0.2mu).

Animals↗
PubMed1976

The Kveim test: analysis of results of tests using colindale (K 12) materials.

Results of an analysis are presented of the salient clinical, pathological, and Kveim-test data of importance in the diagnostic assessment of 839 patients in whom a Kveim test was made as part of their routine clinical investigation. From these analyses the following significant observations can be made: 1) The age distribution and negative tuberculin results in patients with sarcoidosis were in keeping with the diagnosis of sarcoidosis, whereas for those in whom a diagnosis other than sarcoidosis was made, they were not. 2) The findings of 64% positive tuberculin results in cases of confirmed sarcoidosis of less than 2 yr known duration and only 39% in those of greater than 2 yr duration are closely similar to those found in international Kveim-test studies reported by Siltzbach in 1966 and Hurley and Bartholomeusz in 1971. 3) The use of the material was helpful in confirming a diagnosis of sarcoidosis in patients with extrathoracic lesions, for positive results were obtained in 33% of those with uveitis 40% of those with erythema nodosum only (findings which are in keeping with those of other studies in the United Kingdom, and 60% among 27 patients presenting with lesions in various sites, including 2 with cranial nerve lesions and one with cardiac arrhythmia. 4) We found only 2 positive reactions (less than 1%) among 221 patients in whom a diagnosis other than sarcoidosis was reached. Clearly these findings show that the Kveim test material. Lots 19 and 22, of spleen K 12 exhibited not only a high degree of reactivity and selectivity for sarcoidosis, but also that they were of considerable practical value as an aid to diagnosis. The finding of only 2(0.9%) positive Kveim tests among 221 patients with diseases other than sarcoidosis is of special interest. Of the different diseases that were ultimately diagnosed only 6 patients tested had lymphoma, only 11 had either pulmonary or lymphatic tuberculosis, and only one had Crohn's disease. Although these numbers are small, it is relevant to compare the Kveim-test data of Lots 19 and 22 of K 12 with those of Lot 5 and of Lot 14 of the same spleen. In validation studies Lot 5 yielded the expected proportion of positive reactions at different stages of sarcoidosis and a negligible proportion of positive reactions with active or quiescent pulmonary tuberculosis or among healthy subjects. However, in subsequent studies in special groups of patients, those with Crohn's disease, ulcerative colitis, or lymphatic tuberculosis, a proportion of the Kveim tests performed with these lots were positive. Within the context of the present field study, the results of these analyses confirm that the last lots of K 12 material exhibited a high degree of selectivity for sarcoidosis and that they emphasize again the practical value of the Kveim tests with suspensions that have undergone careful validation.

Adolescent↗
PubMed1976

Validation and standardization of Kveim test suspensions prepared from two human sarcoid spleens.

Single lots of a Chase-Siltzbach type I Kveim test material from each of two sarcoid spleens and designated lot 5 of spleen K12 and lot 1 of spleen K13 have been validated alongside a single lot (lot 10) of a 'standard' suspension provided by Dr L. E. Siltzbach and prepared identically from the spleen of patient J (SPLEEN J) in New York. Additionally, a half-dilution of lot 5, K12, was included in this comparison. The reactivity of each suspension was assessed among patients with active and inactive sarcoidosis. The selectivity of each suspension for sarcoidosis was assessed similarly by comparison with results in patients with active and quiescent pulmonary parenchymal tuberculosis and in healthy subjects. All patients were closely matched and two Kveim tests were made in each subject according to a prearranged statistical design. The reactivity of the K12, K12 1/2 dilution, and K13 suspensions among patients with active and inactive sarcoidosis was closely similar to that with the 'standard' S10 suspension and in accordance with the expected proportions of reactions in patients at different stages of sarcoidosis. The K12, K13, and 'standard' S10 suspensions yielded a negligible proportion of positive reactions among patients with active and quiescent pulmonary tuberculosis and among healthy subjects: thus, as judged by these tests each suspension showed a high degree of selectivity for sarcoidosis. The results of this validation study are discussed in relation to the results of other studies in which lots 5 and 14 of K12 and early and late batches of a suspension prepared from another sarcoid spleen at the Commonwealth Serum Laboratories designated CSL and provided by Dr T.H. Hurley in Melbourne were employed. Using lot 5 of K12 positive reactions were found in an appreciable proportion of patients with Crohn's disease, ulcerative colitis, and tuberculous lymphadenitis. A closely similar rate of positive reactions was encountered among patients with Crohn's disease following tests with batch 0025 of CSL suspension and with another lot (lot 14) derived from spleen K12. A close concordance of results was obtained with lot 5(K12) and with batch 0042 CSL among patients with ulcerative colitis, but at a lower rate of reactivity. We conclude that positive reactions also occur in some diseases other than sarcoidosis and consider that the difficulties in determining the criteria for an acceptable test suspension become increasingly apparent as additional Kveim tests are made with one particular lot and with seqential lots of material from a 'validated' tissue source.

Adult↗
PubMed1975

Antibody to herpes-like virus in sarcoidosis.

Anti-hepes-like virus antibody titers in samples of serum drawn from 70 consecutive patients at the time of diagnosis of sarcoidosis were compared with those found in control subjects without sarcoidosis or granulomatous disease, matched for age, sex, and race. Antibody was detected in all 70 sarcoid and control sera; in general, titers were higher for the sarcoid patient than for the matched control subject, but the difference in the geometric mean titer was only 0.5 of a twofold dilution step. Only 21 (30 per cent) of the sarcoid and 8 (11 per cent) of the control sera had titers greater than or equal to 1:600. The difference in the geometric mean titer between patient and control subject did not vary significantly with sex, race, or type of sarcoidosis. A second sample of serum was drawn from 45 of the 70 sarcoid patients after an interval varying from 18 to 60 months. Among these 45 patients the titers were virtually unchanged: 39 (87 per cent) had the same titer on the second occasion, 4 were higher by one dilution, and 2 were lower by one dilution. There was no correlation between the titer of the initial sample of serum and the progression, regression, or attainment of inactivity of the sarcoidosis. From this study we conclude that the elevated anti-herpes-like virus antibody titer found in patients with sarcoidosis are most likely to be related to the ability of these patients to show enhanced humoral antibody responses.

Antibodies, Viral↗
PubMed1975

Experimental animal studies of the etiology and pathogenesis of Crohn's disease.

Nineteen New Zealand White Rabbits were inoculated intramurally into the intestine with a 100- or 0.2-mu filtrate of homogenate of fresh ileum or colon from each of 6 patients with histologically confirmed Crohn's disease and compared with 22 animals injected with homogenates of normal ileum or colon from each of 5 patients; 4 sham controls were also included. The animals receiving Crohn's homogenates put on less weight than the controls; mucosal ulceration, ileal thickening, and abscess formation were seen in 8 animals and granulomatous changes evolved in 9. No significant macroscopic abnormalities or granulomatous changes were present in any of the 22 control inoculated rabbits. Successful first passage was achieved from 6 of 11 rabbits. The results of these experiments therefore confirm and extend those of our earlier reports and demonstrate that the transmissible agent or agents responsible must approximate to the size of a virus or be capable of being deformed to pass through a 0.2-mu filter.

Animals↗
PubMed1974

Human myeloma marrow cells in immunologically deficient mice.

Intact human bone marrow cells from 7 patients with myelomatosis were inoculated intravenously into adolescent CBA mice rendered immunologically deficient by thymectomy followed by total body irradiation (600 rad). Each inoculum of human myeloma marrow cells and subsequent passages of intact mouse marrow and spleen cells resulted in the presence of morphological changes in the marrow, spleen and peripheral blood of a proportion of these mice which were closely similar to those seen in the human donor. A substantial amount of human immunoglobulin (IgG and IgA) was detected in the sera of some of the mice showing morphological changes. Mice prepared identically but remaining uninoculated or receiving intact human bone marrow cells from 3 patients with no evidence of haematological malignancy showed none of these changes when examined after similar intervals.There are at least 3 possible explanations for these findings: in mice receiving human myeloma marrow cells they might be accounted for by the persistence and replication of these cells in an immunologically deficient host. In mice receiving a first, second or third passage of abnormal mouse marrow and spleen cells they might similarly be accounted for by the survival and multiplication of a stem cell secreting both mouse and human immunoglobulins. Alternatively, the mouse stem cells may in some way have been transformed following infection by a transmissible agent originally present in the myeloma donor marrow cells.

Animals↗
PubMed1974

Sarcoidosis.

Explore the source record for details and available documents.

Antibody Formation↗