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Biomedical subjects

K A Maclennan

Publications and source records attributed to K A Maclennan.

At least 19 recordsLinked to original sources
PubMed2005

Enhanced large intestinal potassium permeability in end-stage renal disease.

The capacity of the colon for potassium (K+) secretion increases in end-stage renal disease (ESRD), to the extent that it makes a substantial contribution to K+ homeostasis. This colonic K+ adaptive response may reflect enhanced active K+ secretion, and be associated with an increase in apical membrane K+ permeability. In this study, this hypothesis was tested in patients with normal renal function or ESRD, by evaluating the effect of barium ions (a K+ channel inhibitor) on rectal K+ secretion using a rectal dialysis technique, and the expression of high conductance (BK) K+ channel protein in colonic mucosa by immunohistochemistry. Under basal conditions, rectal K+ secretion was almost threefold greater (p < 0.02) in ESRD patients (n = 8) than in patients with normal renal function (n = 10). Intraluminal barium (5 mmol/l) decreased K+ secretion in the ESRD patients by 45% (p < 0.05), but had no effect on K+ transport in patients with normal renal function. Immunostaining using a specific antibody to the BK channel alpha-subunit revealed greater (p < 0.001) levels of BK channel protein expression in surface colonocytes and crypt cells in ESRD patients (n = 9) than in patients with normal renal function (n = 9), in whom low levels of expression were mainly restricted to surface colonocytes. In conclusion, these results suggest that enhanced colonic K+ secretion in ESRD involves an increase in the apical K+ permeability of the large intestinal epithelium, which most likely reflects increased expression of apical BK channels.

Adult↗
PubMed2005

Surgical pathological second opinion in thyroid malignancy: impact on patients' management and prognosis.

OBJECTIVES: To evaluate the effect of inter-institutional surgical pathology review of thyroid cancer on patients' treatment and prognosis. METHODS: All cases referred to the Institute of Pathology at Leeds for thyroid pathology review between January 2001 and March 2003 were included. The referring pathologists reports were compared to those produced in the MDT meeting by the expert pathologist. Whenever there was disagreement a third expert opinion was sought who was blinded for both diagnoses. Effects on management and prognosis were evaluated if there was disagreement. RESULTS: Of the 66 patients reviewed, 12 (18%) had a different pathological diagnosis (kappa=0.33). Two had their diagnosis changed from malignant to benign and a further two from benign to malignant. Eight patients had their prognosis downgraded and four upgraded after histopathological review. Five patients had their management affected by the new pathological diagnosis. CONCLUSION: A second opinion of surgical pathology for thyroid tumours can result in major therapeutic and prognostic modifications. All cases of suspected thyroid cancers should be reviewed in a multidisciplinary meeting supported by pathologist with experience in thyroid pathology.

Diagnostic Errors↗
PubMed2002

Diffuse large B-cell lymphoma: a clinicopathologic analysis of 444 cases classified according to the updated Kiel classification.

The purpose of this study was: to compare the survival of diffuse large B-cell lymphomas (DLBCL) stratified according to the up-dated Kiel classification. A retrospective study of a cohort of 1378 cases was organized in 1996 by the Non-Hodgkin's Lymphoma Classification Project, and the DLBCL were classified according to the updated Kiel classification. The distribution of the different types and subtypes was as follows: centroblastic (CB, 85.4%), composed of the polymorphic (CB-PM, 58.6%), monomorphic (CB-MM, 17.1%) and multilobated (CB-ML, 9.7%) subtypes; immunoblastic (IB, 11.2%), with (8.3%) or without (2.9%) plasmacytoid differentiation; and anaplastic large cell lymphoma (ALCL) of B-cell type (3.4%). The rate of diagnostic agreement between pathologists was 78% for CB and 65% for IB lymphoma. The 5-year overall survival (OAS) for the entire group was 47% and the 5-year failure-free survival (FFS) was 42%. No significant differences in survival were found between the three major groups (CB, IB, ALCL). However, the 5-year OAS and FFS of patients with DLBCL not containing immunoblasts (CB-MM+CB-ML) was 51 and 52%, respectively, and was significantly better than the survival of those containing immunoblasts (CB-PM+IB+ALCL), which was 44 and 38% (p = 0.06 and p = 0.037), respectively. These results did not appear to be due to differences in the clinical features of the two groups, and was most significant for patients with low stage or low risk disease. However, histologic subtyping was not an independent risk factor for the entire group by multivariate analysis. In conclusion, patients with CB-MM and CB-ML (without immunoblasts) had a significantly better OAS and FFS than those with CB-PM, IB and ALCL (with immunoblasts). Therefore, we conclude that additional studies are still needed to further evaluate the importance of immunoblastic differentiation in DLBCL.

Adolescent↗
PubMed2001

ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial.

The purpose of this randomized trial was to compare the efficacy of 6 cycles of prednisolone, Adriamycin (doxorubicin), bleomycin, vincristine (Oncovin) and etoposide (PABlOE) with 3 cycles of PABIOE that alternate with 3 cycles of chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) in patients with advanced Hodgkin's disease. Between October 1992 and April 1996, 679 patients were entered onto the study. 41 of these did not match the protocol requirements on review and were excluded from further analysis, most of these being reclassified as NHL on histological review. Of the remaining 638 patients, 319 were allocated to receive PABIOE and 319 were allocated to receive ChlVPP/PABlOE. The complete remission (CR) rates were 78% and 64%, for ChlVPP/PABlOE and PABIOE respectively after initial chemotherapy (P< 0.0001). 124 patients were re-evaluated subsequently following radiotherapy to residual masses. The CR rates changed from 78% to 88% for ChlVPP/PABlOE and from 64% to 77% for PABlOE when re-evaluated in this manner (treatment difference still significant, P = 0.0002). The treatment associated mortality in the PABlOE arm was 2.2% (7 deaths), while there were no such deaths in the ChlVPP/PABlOE arm (P = 0.015). The failure-free survival was significantly greater in the ChlVPP/PABlOE arm (P< 0.0001) as was the overall survival (P = 0.01). The failure-free and overall survival rates at 3 years were 77% and 91% in the ChlVPP/PABlOE arm, compared with 58% and 85% in the PABIOE arm, respectively. These results indicate that ChlVPP alternating with PABIOE is superior to PABIOE alone as initial treatment for advanced Hodgkin's disease.

Adolescent↗
PubMed2000

A randomized British National Lymphoma Investigation trial of CHOP vs. a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma.

BACKGROUND: Between 1987 and 1991, the British National Lymphoma Investigation randomized 459 patients with non-Hodgkin's lymphoma with a large-cell component to either CHOP or the PACEBOM regimen. PATIENTS AND METHODS: Four hundred fifty-nine eligible patients were included in this trial, four hundred one with diffuse large-cell lymphoma and fifty-eight with diffuse mixed-cell lymphoma according to the Working Formulation. Two hundred twenty-six patients were randomized to receive CHOP and two hundred thirty-three to receive PACEBOM. The two arms of the trial were well balanced for all potential prognostic factors. RESULTS: The complete remission rate with PACEBOM was 64% and with CHOP 57% (NS). At eight years, the actuarial cause specific survival (CSS) in the PACEBOM arm is 59% compared to 49% in the CHOP arm (P = 0.09). Patients < 50 years of age fared significantly better in the PACEBOM arm both for CSS and overall survival (P = 0.002) and the CSS was also significantly improved in stage IV disease (P = 0.02). CONCLUSIONS: The mature data from this trial suggest that an etoposide-containing multi-agent weekly regimen can be superior to CHOP.

Adolescent↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1984

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↗
PubMed1984

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↗