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Biomedical subjects

K A Maclennan

Publications and source records attributed to K A Maclennan.

14 recordsLinked to original sources

The phenotypic changes in tumour infiltrating lymphocytes and tumour cells following intra-arterial infusion of interleukin-2 in patients with squamous cell carcinoma.

This study evaluates the morphological and phenotypic changes that occur in squamous cell carcinoma of the head and neck when local infusions of interleukin-2 (IL-2) are given. Twelve patients were treated with a range of doses of IL-2 (3 x 10(3) to 3 x 10(6) international units/day) by continuous intra-arterial infusion for 10 days. Biopsies of the tumour were taken pre- and 48 h post-therapy, snap-frozen, cut, and examined histologically and immunocytochemically. Local infusions of IL-2 increase the numbers of antigen-presenting Langerhans cells (CD1a-positive) and infiltrating lymphocytes, predominantly of the CD3 and CD4 (T-helper) phenotypes. Locally infused IL-2 results in the expression of MHC (major histocompatibility complex) class II antigens on the surface of the tumour cells, capillary and post-capillary endothelial cells, and peri-tumoural macrophages. Intratumoural NK (natural killer) cells and CD8-positive (T-cytotoxic) infiltrating lymphocytes were not increased by this therapy and CD25 (IL-2 receptor) was only increased in those patients treated at the lower dose levels. The system of intra-arterial cytokine infusion into head and neck tumours developed in this study is a useful model to examine the biological effects of cytokines, since in vivo they are mainly produced and act locally. Furthermore, the infused tumours are easily accessible to biopsy. The results from studies such as this may influence the design of tumour-targeted cytokine gene therapy programmes.

Adult

Signet-ring cell lymphoma of bone marrow.

A case of signet-ring cell lymphoma affecting bone marrow is reported. The tumour presented as multiple lytic lesions in the lumbosacral spine. A bone biopsy specimen showed the typical appearances of signet-ring cell lymphoma, and the cells stained positively with antiserum to CD20, though neither immunoglobulin light or heavy chains could be shown within the vacuoles. The patient subsequently responded to chemotherapy.

Bone Marrow

Vascular changes in irradiated lungs: a morphometric study.

The lungs from eight patients who had received thoracic irradiation for the treatment of malignant disease have been studied and a morphometric analysis of the vascular changes present has been made. We found a marked difference between the changes we observed in the pulmonary vessels and those described in systemic vessels after exposure to irradiation. In the former the changes are more pronounced in the venous circulation, and in the latter they are described as being almost confined to the arteries. This difference is a reflection of the difference in oxygen saturation of the blood in the two types of vessels. We suggest that this difference can be explained by the possible role of super-oxide free radicals in the generation of these effects.

Humans

Systemic disturbance in Hodgkin's disease and its relation to histopathology and prognosis (BNLI report No. 30).

Systemic disturbances in Hodgkin's disease at presentation are not only manifested by 'B' symptoms (weight loss, fever, and night sweats), but are also mirrored in the peripheral blood as raised sedimentation rate, low haemoglobin, low albumin, and abnormal lymphocyte counts. Such systemic disturbance is more common than consideration of classical 'B' symptoms alone would suggest. In a series of 840 patients, 88% had some form of systemic disturbance on these criteria. Survival after treatment was found to be closely and inversely related to the degree of systemic disturbance present before treatment. Patients with no evidence of such disturbance had an almost 100% survival at 10 years. In the absence of 'B' symptoms the sedimentation rate was the most useful prognostic blood parameter, enabling about one third of the patients to be identified as having an excellent chance of survival, and identifying a further 12% as having a survival almost identical to that of patients with 'B' symptoms. The latter patients were those with a sedimentation rate of 60 mm/h or greater, and it is suggested that the term 'Systemic Symptoms' should be broadened to include a sedimentation rate of this magnitude. The degree of malignancy of the tumour, as reflected by histopathology, plays a dominant role in determining the amount of systemic disturbance in the host. However, the amount of disturbance varies amongst individual patients with the same histopathological subtype, reflecting either differences in the malignancy of the tumour within such subtypes, or differences in the constitution of the host.

Blood Sedimentation

Hodgkin's disease in childhood: the British National Lymphoma Investigation experience (BNLI Report No 27).

The experience of the British National Lymphoma Investigation in the treatment of 68 children with Hodgkin's disease is reported over a 14 year period from 1970. The presenting histology was reviewed by a single histopathologist; 87% of the cases were classified as nodular sclerosis (NS) and further subdivided into NSI (53%) and NSII (35%). Primary treatment consisted of local (involved field) or prophylactic (extended field) irradiation, combination chemotherapy alone or low dose irradiation and chemotherapy. An overall 5 year survival of 87% was achieved and a 5 year relapse-free survival of 64%. Eight deaths were reported during the study, all of which occurred in children who presented with NSII histology. Each child was in relapse and undergoing chemotherapy at the time of death. This histological subtype was also associated with both a lower complete remission rate and a reduced response to second line chemotherapy.

Adolescent

The management of primary carcinoma of the fallopian tube. Experience of 40 cases.

Forty patients with primary tubal cancer were treated at the Middlesex and Mount Vernon Hospitals between 1951 and 1981. Actuarial 5-year survival was seen in 68% of 10 Stage I cases, 39% of 17 Stage II cases, and 21% of 11 Stage III cases, and this experience is consistent with other reported postwar series. The disease was found to exhibit some similarity to ovarian cancer in terms of its mode of spread and response to radiation and cytotoxic agents. Transcoelomic spread was identified as the major cause of treatment failure, and management proposals have been structured around its detection and treatment.

Adult

Prenatal diagnosis of three cases of severe combined immunodeficiency: severe T cell deficiency during the first half of gestation in fetuses with adenosine deaminase deficiency.

The prenatal diagnosis of severe combined immunodeficiency (SCID) was made in three fetuses by staining fetal blood obtained at fetoscopy with a panel of monoclonal antibodies. There were less than 100 T cells/mm3 of fetal blood in these three cases compared to 2,500/mm3 in 14 immunologically normal fetuses. Cells bearing the cortical thymocyte antigen (NA1/34) were not detected in any of the normal or affected fetal blood samples. Two of the affected fetuses were also homozygous for a deficiency of adenosine deaminase (ADA) with undetectable levels of red cell ADA. All three affected fetuses were aborted and postmortem tissue was obtained in two cases. In both of these cases the thymus was markedly hypoplastic and contained no lymphoid cells. One of these fetuses was homozygous for ADA deficiency and the virtual absence of T cells or thymocytes during the second trimester of pregnancy indicates that placental access to the maternal circulation does not prevent damage to the T lineage stem cells in this disease. Prenatal diagnosis of SCID has previously only been possible in patients with a defined metabolic defect such as ADA deficiency, but these studies indicate that prenatal diagnosis now may be offered for most at risk pregnancies.

Adenosine Deaminase

The response to treatment of nodular sclerosing Hodgkin's disease with extranodal involvement.

A study of the relationship between extranodal involvement and subsequent relapse has been undertaken in 32 patients with Stage IV nodular sclerosing Hodgkin's disease treated by chemotherapy. All patients were investigated and treated according to protocols of the British National Lymphoma Investigation. The most significant observation is that patients classified Stage IV by virtue of contiguous extranodal extension from bulky nodal lesions are inadequately treated by chemotherapy alone. Overall, 11 out of 12 (E) stage patients had residual or recurrent disease following quadruple chemotherapy. Four of these patients have since been rendered disease-free by radiotherapy.

Adolescent