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Biomedical subjects

L McLean

Publications and source records attributed to L McLean.

At least 55 records · Page 3Linked to original sources

Assessment of a specimen mount for biopsy of impalpable breast lesions.

Biopsy of the impalpable breast lesion is an increasing part of the surgical workload as a result of the National Breast Cancer Screening Programme. A specimen mount card has been described to orientate such specimens in three dimensions prior to radiological and pathological examination. Experience with 243 biopsies in this unit has shown it to be a useful aid in determining completeness of excision. It may also be used as a guide to further surgery when excision is incomplete and breast conservation is the treatment option of choice.

Biopsy↗

Unilateral increase in mammographic density with hormone replacement therapy.

Two cases of localized unilateral increase in mammographic density are described in women who had commenced hormone replacement therapy (HRT) just before or within several weeks of their first normal screening mammogram. The increase in density at a subsequent screen required recall to an assessment clinic to exclude cancer in the affected breast. The relationship of HRT to mammographic density is discussed.

Breast↗

Case of the month: a case of forgetfulness?

An obese 24-year-old man was admitted following a road traffic accident, during which he crashed into several cars and a shop. He had not been drinking alcohol, yet did not recall the incident. The family had noticed recent odd behaviour, episodic aggression and a glazed look at times. Apart from a minor whiplash injury, he was uninjured and clinically normal. A computed tomography (CT) head scan and encephalo-electrography were both normal. Routine investigations were unremarkable apart from a fasting glucose 0.9 mmol l-1. In view of the presenting symptoms and fasting hypoglycaemia, a CT scan of the abdomen was performed (Figure 1). What does this show?

Adult↗

Should breast biopsy cavities be drained?

A total of 112 women was entered into a randomised study to investigate the effects of suction drainage on haematoma formation in breast biopsy wounds. Of 107 evaluable patients, 52 received drainage and 55 had no drain. The wounds were examined 1 week after operation when the volume of wound haematoma was measured using ultrasonography. Haematomas were present in 48 (87%) patients with undrained wounds compared with 34 (65%) patients with drained wounds (P = 0.014, chi 2 test). Median haematoma volume was 20 ml (range 0-172.5 ml) in the undrained group compared with 2 ml (range 0-100 ml) in the drained group (P = 0.001, Mann-Whitney U test). There was one wound infection in each group. There was no difference in median pain score or duration of pain between the groups. While suction drainage significantly reduces the incidence and volume of wound haematomas, this does not appear to influence outcome.

Adult↗

Clinical and radiographic results of the Muller straight stem used as a press-fit.

Prior to the introduction of porous coating, 21 patients had 24 ME Muller straight-stem femoral prostheses inserted as a press fit for the treatment of osteoarthrosis. Five hips have been revised for aseptic loosening; the remaining 19 prostheses are still in situ after a mean of 7.3 years (range, 6.2-8.3 years). A prospective clinical assessment has been undertaken using a modified Harris hip score, with scores increasing on average from a preoperative 43 to a postoperative 79. Eighteen of the 19 remaining hips are functioning well. Variable distances of subsidence are evident in 10 hips. Despite the use of a prosthesis that was not designed for cementless proximal wedge fitting, the results indicate an exceptionally low incidence of bone resorption and lysis. Unlike cemented and some porous-coated prostheses, stress shielding and osteopenia were not a feature in this series.

Aged↗

Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles.

The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24-hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reaction of antibody to mycobacterial 65 kDa heat-shock protein with human chondrocytes.

We report on the reactivities of four monoclonal antibodies generated against mycobacterial proteins to human chondrocytes, cells in cartilage which may be subject to immune attack in rheumatoid arthritis. Only one of the monoclonal antibodies, ML30, which had been shown previously to react with a human homologue to heat-shock protein (hsp), reacted strongly to chondrocytes. By immunocytochemical methods using fixed chondrocytes, ML30 reacted to cytoplasmic constituents in a granular pattern. There were no marked qualitative differences in the staining intensities and patterns of chondrocytes kept at ambient temperatures and those subjected to 42 degrees C heat treatment. No significant staining was observed with normal peripheral blood mononuclear cells. By indirect immunofluorescence, the distribution of ML30 reactive constituents was very low on the cell surface. Reactivities of each of the monoclonal antibodies were tested on frozen sections of cartilage. Significant reactivity was found only with ML30, and the staining was only associated with chondrocytes, not with the cartilage matrix surrounding the cells. These findings may have significance in view of the possibility that an hsp homologue may be a target for inciting or perpetuating the autoimmune process in rheumatoid arthritis.

Antibodies, Monoclonal↗

Effect of MK-458 (HPMC) in Parkinson's disease previously untreated with dopaminergic drugs. A double-blind, placebo-controlled multicenter study.

Ninety-four patients with early Parkinson's disease were investigated in a double-blind, placebo-controlled evaluation of MK-458 [hydroxypropyl methylcellulose/lactose matrix (HPMC)], a sustained release formulation of a novel naphthoxazine compound with selective D-2 dopamine receptor agonism. Patients were previously untreated with dopaminergic drugs. Efficacy was assessed by clinical rating scales and by patient self-evaluation. MK-458 (HPMC) caused a significant decrease in most parkinsonian symptoms. Though disability rating scores were lowered by the drug, the scores did not differ significantly from placebo. However, statistically significant improvement occurred with MK-458 (HPMC) on both the physician and the patient global assessments. Adverse reactions such as nausea and vomiting, sedation, confusion, and hallucinations occurred more with MK-458 (HPMC) than with placebo. MK-458 (HPMC) possesses antiparkinsonian efficacy in early Parkinson's disease; however, side-effects are frequently associated with its use. Selective D-2 receptor agonists, such as MK-458 (HPMC), may not be the ideal treatment as monotherapy for Parkinson's disease.

Aged↗

Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes.

The L1 gene of human papillomavirus type 16 (HPV-16) driven by the vaccinia virus major late 4b gene promoter has been inserted into three different sites of the vaccinia virus genome. Insertion into the thymidine kinase (TK) gene was achieved by selection of TK- mutants in BUdR on TK- cells. Insertion into two vaccinia virus serine protease inhibitor (serpin) genes was achieved by co-insertion of the Escherichia coli xanthine guanine phosphoribosyltransferase gene linked to the vaccinia virus 7.5K promoter and selection of mycophenolic acid-resistant recombinant viruses. Each recombinant virus expressed a 57K L1 protein at similar levels and with similar kinetics. However, immunization of mice with these recombinant viruses induced different levels of antibody to the L1 protein. Viruses lacking serpin genes B13R and B24R induced significantly higher antibody levels than did viruses lacking the TK gene. The presence of functional B13R and B24R gene products is therefore somehow immunosuppressive at least for antibody responses to the L1 protein of HPV-16.

Animals↗

Role of immunity to mycobacterial stress proteins in rheumatoid arthritis.

'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis.

Animals↗

Identification and characterization of a pancreatic intrinsic factor in the dog.

An intrinsic factor has been identified in the canine pancreas, and output and properties of this protein have been compared with those of gastric intrinsic factor in the dog. Mean concentrations of intrinsic factor and peak outputs per minute were approximately 5- to 10-fold higher in pure pancreatic juice after stimulation with secretin and cholecystokinin, respectively, than in pentagastrin-stimulated gastric juice. Purified gastric and pancreatic intrinsic factors had an identical molecular mass of 65 kDa, estimated by gel filtration on Sephacryl S-200, while sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated single bands corresponding to 53 kDa. Immunoblots showed that rabbit polyclonal antiserum to canine gastric intrinsic factor cross-reacted with canine pancreatic intrinsic factor. Gastric and pancreatic intrinsic factor-cyano[57Co]cobalamin complexes exhibited comparable association constants for ileal receptors in canine brush-border vesicles, while there was minimal binding to jejunal vesicles. These findings demonstrate that the canine pancreas is an important source of an intrinsic factor that closely resembles gastric intrinsic factor in the dog.

Animals↗

Circulating concentrations of trypsin-like immunoreactivity and activities of lipase and amylase after pancreatic duct ligation in dogs.

The possibility that assay of circulating trypsin-like immunoreactivity (TLI) could assist in the diagnosis of acute pancreatitis in dogs has been examined by assaying plasma TLI concentrations after pancreatic duct ligation and comparing the results with plasma activities of lipase and amylase. Venous blood samples were obtained from 8 dogs before surgery, then daily for 5 days and at 14 days after ligation of pancreatic ducts. Plasma concentrations of TLI increased within 24 hours and tended to peak before and to decrease more rapidly than activities of lipase and amylase, remaining greater than the control range for 5 days in all but 2 dogs. Plasma lipase and amylase activities increased together and remained greater than the control range in all dogs for 5 days after surgery. Regression analysis of all postoperative data indicated significant correlations between concentration of TLI and lipase activity (r = 0.67, P less than 0.001), concentration of TLI and amylase activity (r = 0.53, P less than 0.001), and between lipase and amylase activities (r = 0.74, P less than 0.001). These findings suggested that assay of TLI may provide an early indication of acute pancreatitis in dogs. Because TLI is specifically pancreatic in origin, high plasma TLI concentration may prove a more reliable indicator of clinical pancreatitis than high activities of amylase or lipase, which may be derived from extrapancreatic tissues.

Amylases↗

Status of an unpaired thiol group on the HLA-B27 epitope.

Sequence analysis and site-directed mutagenesis of HLA-B27 indicate an unpaired cysteine at position 67 of the hypervariable region corresponding to its serologically defined, disease-associated epitope. We investigated whether chemical modification of this thiol group affected the serological reactions of B27. B27-positive cells were treated with thiol-blocking agents and then tested for recognizable B27 expression. Anti-HLA-B27 alloantisera and monoclonal antibodies were used in cytotoxicity, absorption, and cellular ELISA (cELISA). The semi-quantitative cytotoxicity-based assays showed some decrease in both B27 and controls. However, cELISA indicated that the inhibition of B27 was significantly greater than control antigens, and dependent on thiol-blocker concentration. This suggests that a proportion of HLA-B27 molecules have a free, reactive thiol at the antibody-defined epitope. Incomplete inhibition by thiol-blocking agents indicates that the remainder are inaccessible.

Antibodies, Monoclonal↗

Biochemical changes in the jejunal mucosa of dogs with exocrine pancreatic insufficiency following pancreatic duct ligation.

The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora.

Alkaline Phosphatase↗

Response of the jejunal mucosa of dogs with aerobic and anaerobic bacterial overgrowth to antibiotic therapy.

Dogs with naturally occurring aerobic or anaerobic bacterial overgrowth have been examined before and after antibiotic therapy in order to assess reversibility of damage to the jejunal mucosa. Histological changes in peroral jejunal biopsies were relatively minor before and after treatment, but sucrose density gradient centrifugation revealed specific biochemical abnormalities that responded to antibiotic therapy. Aerobic overgrowth was initially associated with a marked loss of the main brush border component of alkaline phosphatase activity; this recovered following treatment, suggesting that aerobic bacteria may cause reversible damage to the hydrophobic region of the brush border membrane. In contrast, anaerobic overgrowth was initially associated with a marked reduction in brush border density, indicative of a considerable fall in the glycoprotein-to-lipid ratio of the membrane. Density increased from 1.17 to 1.21 g/ml after antibiotic therapy, consistent with recovery from this relatively severe damage to the brush border caused by anaerobic bacteria. Reductions in soluble and peroxisomal catalase activities which could compromise mucosal protection against free radicals in dogs with aerobic overgrowth, and a loss of particulate malate dehydrogenase activity indicative of mitochondrial disruption in dogs with anaerobic overgrowth, were also reversed after treatment. These findings indicate that aerobic and anaerobic bacterial overgrowth can result in contrasting but potentially reversible damage to the jejunal mucosa which would not be detected by conventional investigative procedures.

Animals↗