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Biomedical subjects

A J Malcolm

Publications and source records attributed to A J Malcolm.

At least 91 records · Page 5Linked to original sources

Immunohistochemical detection of neuroblastoma in frozen sections of bone marrow trephine biopsy specimens.

Frozen sections from bone marrow trephine biopsy specimens from children with disseminated neuroblastoma were stained using the monoclonal antibody UJ13A. An immunoalkaline phosphatase technique was the preferred staining method. Acceptable histological detail was obtained from this material and deposits of tumour cells detected. Some apparently fibrous tissue was also stained by this antibody. The results show that this immunohistological approach is feasible and provide encouragement for its addition to the range of investigations currently available for assessing the marrows of children with this disease.

Antibodies, Monoclonal↗

Technique for identifying cutting artefacts in sections of undecalcified bone biopsy specimens.

Areas of fragmentation found in trabecular and cortical bone of iliac crest biopsy specimens have been described as bone quality defects and were thought to be the major factor responsible for femoral neck fractures. These appearances have also been regarded as cutting artefacts and to resolve this difference of opinion consecutive sections cut at right angles to each other in biopsy specimens from 15 patients with femoral neck fractures were compared. Sections were assessed by four independent observers; agreement by at least three was required before an area was accepted as a bone quality defect. In all, 270 were identified. Of the 161 found in sections cut parallel to the cortices, there were only 20 (12%) in coincident areas in consecutive sections. This study shows conclusively that areas of fragmentation previously described as bone quality defects are not artefacts which may be created or excluded depending on the plane of section.

Aged↗

Growth hormone in polymethylmethacrylate cement.

The in vitro release of human growth hormone (hGH) from polymethylmethacrylate bone cement was measured for up to 40 days using a specific enzyme-linked immunosorbent assay. In rabbits, hGH-loaded bone cement was inserted into one distal femur and plain cement was inserted into the contralateral distal femur as a control. The rabbits were killed at time intervals of one, two, and four months after surgery and the distal femurs embedded whole for histology. Quantitative histomorphometry indicated there was a greater percentage of osteoid present at the hGH-loaded cement surface than at the plain cement surface one month after implantation. The hGH released from bone cement may stimulate osteogenesis and new bone formation, thus improving the strength of the bone-cement interface.

Animals↗

A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss.

A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin. Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died for liver failure after 3 months. Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients. No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p less than 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p less than 0.05), as did trabecular bone volume (-6% vs. -2.8%, p less than 0.005) and resorption surface (-11% vs. +2%, p less than 0.02) on serial bone biopsy. Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the "cost/benefit" ratio.

Adult↗

Aneurysmal bone cyst of the zygomatic bone.

Aneurysmal bone cysts are a rare finding in the facial bones and jaws. Only one previous case of this entity affecting the malar bone could be found in the literature. Ultrasound and isotope scan features of this entity are described.

Bone Cysts↗

Improved method for immunoperoxidase detection of membrane antigens in frozen sections.

The visualisation of membrane antigens in frozen sections using metal-enhanced 3,3'diaminobenzidine (DAB) was investigated. Particular attention was paid to the degree of reaction enhancement, the disruptive effect on morphological detail, and the ease of the techniques. The best result was obtained using nickel-modified DAB at pH 6.0 to develop the peroxidase enzyme, with further enhancement in cobalt chloride at neutral pH. Silver methenamine enhancement is also possible but can give rise to non-specific or background staining.

3,3'-Diaminobenzidine↗

The effect of maturation and anterior cruciate ligament transection on the level of keratan sulfate in the serum of dogs.

The reactivity of 2 monoclonal antibodies, D1B2 and 7D1, to keratan sulfate is described. The reaction of both monoclonal antibodies to intact A1D1 proteoglycans was inhibited by isolated keratan sulfate chains. However, 7D1 was less reactive with the keratan sulfate chains bound to ELISA plates than it was to intact proteoglycan. The amount of keratan sulfate was determined in sera of 27 dogs (8 nonoperated, 6 sham operated and 13 ligament transected) between the ages of 305 and 691 days using these monoclonal antibodies in an inhibition ELISA. The level of keratan sulfate as measured by D1B2 but not that by 7D1 decreased significantly with age. The concentration of keratan sulfate was relatively constant between the ages of 450 and 691 days. When controlled for age, no apparent difference could be shown in the level of keratan sulfate in the serum of the dogs as a result of the procedure (ligament transection or sham operation) or time after operation.

Aging↗

Expression of MHC class I and II antigens by keratinocytes and enterocytes in acute graft-versus-host disease. Newcastle Bone Marrow Transplant Group.

The expression of MHC class I and subgroups of class II antigens by keratinocytes and enterocytes has been investigated in patients receiving autologous and allogeneic bone marrow transplants. Allogeneic recipients with graft-versus-host disease (GVHD) expressed all the class II antigens HLA DR, DP and DQ more frequently than pretransplant patients, autologous or allogeneic recipients without GVHD post-BMT (p less than 0.01). Staining for DP and DQ was never detected without DR being present. Whenever there was a lymphocytic infiltrate in the epidermis or single cell necrosis in the gut, DR was expressed on the epithelium. There was no difference in class I expression in GVHD. This study further increases the immunopathological characterization of acute GVHD which may improve the understanding of its pathogenesis.

Acute Disease↗

Metabolic bone disease in primary biliary cirrhosis at presentation.

Metabolic bone disease, particularly osteoporosis, is a complication of advanced primary biliary cirrhosis, but the extent of the problem is unclear. We present 33 patients who were investigated for bone disease at the time of diagnosis of their liver disease and who had received no prior treatment likely to influence their bones. Iliac crest bone biopsy showed no patient with osteoporosis, and mild osteomalacic changes in 1 patient. Slight elevations in appositional rate, osteoid volume, and resorption surface were compatible with a state of high bone turnover. Photon absorptiometry revealed a low forearm bone mineral content in 3 of 25 patients, calcium absorption was below normal in 14 of 24 patients, and there was evidence of fat malabsorption in 11 of 25 patients. Five patients also had low serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Thus, little evidence of significant metabolic bone disease was found in this group by these methods, but abnormalities were seen, such as poor calcium absorption, that may predispose to its later development.

Adult↗

Cytogenetic abnormalities in a primitive neuroectodermal tumor.

Two distinct karyotypically abnormal cell lines were observed in cultures of a primitive neuroectodermal tumor. One involved multiple chromosome rearrangements, and the other an inversion of chromosome #7 and a t(3;10) showing an interstitial deletion of 3p; del(3)(p1?4p1?2). None of these rearrangements have been reported in previous descriptions of primitive neuroectodermal tumor karyotypes.

Child↗

Epidermal growth factor receptor status of histological sub-types of breast cancer.

The histological breakdown of a consecutive series of 264 surgically resected malignant lesions of the breast was studied. Oestrogen and epidermal growth factor receptor status was quantified and presented along with size and lymph node status of the non-ductal lesions. Those non-ductal tumours containing EGF receptors have all recurred within two years of resection. Twenty-one percent of the lobular carcinomas contained EGF receptors compared to 34% of ductal carcinomas. EGF receptor status appeared to be associated with an increased risk of early recurrence and death whatever the histological sub-type of the breast cancer.

Breast Neoplasms↗

Class II antigen expression by keratinocytes and enterocytes--an early feature of graft-versus-host-disease.

HLA-DR expression by keratinocytes and enterocytes was studied in 23 patients undergoing BMT (12 autologous; 11 allogeneic). Two monoclonal antibodies were used to detect the HLA-DR antigen. Only in two patients before transplant and in one following autologous BMT was HLA-DR expressed on keratinocytes. Of 11 allogeneic recipients, 7 developed clinical GVHD, and HLA-DR-positive keratinocytes were seen in 6 of these. HLA-DR was expressed by enterocytes in 5 patients with GVHD and 4 of these also showed HLA-DR expression by keratinocytes. HLA-DR expression by keratinocytes correlated well with clinical GVHD. Expression of this antigen by enterocytes was associated with characteristic histological appearances of GVHD, even in the absence of intestinal symptoms. A combination of traditional and immunocytochemical techniques offers a sensitive and accurate method of confirming GVHD before it becomes florid.

Epidermal Cells↗

Cytogenetic investigations of solid tumours of children.

The association of non-random chromosome abnormalities with solid tumours of childhood may improve accuracy of diagnosis and prognosis and lead to a better understanding of their biology. In a pilot study in the Northern region of England fresh tumour biopsy specimens were obtained from 39 to 72 consecutive solid tumours in children who presented over a period of 21 months. Cytogenetic analysis was possible in 33 and clonal chromosomal abnormalities were detected in nine. In addition, seven of 10 tumours investigated after treatment were abnormal. Ten of these 16 abnormal karyotypes have not previously been described. This pilot study has shown that a concerted investigation of tumour cytogenetics is possible. A multicentre study is essential if our knowledge of basic tumour cytogenetics is to progress.

Biopsy↗

Histological features of skin and rectal biopsy specimens after autologous and allogeneic bone marrow transplantation.

The histological appearances of skin and rectal biopsy specimens were studied in 31 bone marrow transplant recipients (13 autologous, 18 allogeneic) before transplant, at 28 days, at six months, and as soon as graft versus host disease (GVHD) was clinically suspected. Grades I and II skin changes were commonly seen in patients before transplant and in the autologous group after transplant, as well as in most of the allogeneic recipients with suspected GVHD. Epidermal lymphocytic infiltration was seen only in allogeneic recipients, with clinical GVHD following transplant, but this was not a consistent finding and no other histological features were seen which would distinguish early GVHD from changes caused by cytotoxic agents. Rectal biopsy specimens, however, were normal in patients before transplant and in autologous recipients at 28 days; single cell necrosis of crypt cells was seen only in six of 13 allogeneic recipients studied after transplant with clinical skin GVHD but no gastrointestinal symptoms. Skin changes greater than I and II are required for the histological diagnosis of GVHD. Rectal changes are more specific and may be present despite a lack of intestinal symptoms.

Adolescent↗

Immunocytochemical detection of tumours of neuroectodermal origin.

Immunocytochemical methods were applied to bone marrow aspirate and cerebrospinal fluid specimens to show cellular reactivity with the monoclonal antibody UJ13A, which recognises an antigen expressed by cells of neuroectodermal origin. The antigen remained stable after air drying and appropriate fixation. In five patients with various neuroectodermal tumours the diagnostic advantages of these techniques were clear; they can be performed even when only very small amounts of diagnostic material are available.

Adult↗