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Biomedical subjects

A R Tanner

Publications and source records attributed to A R Tanner.

At least 37 records · Page 2Linked to original sources
PubMed1985

The clinical value of rapid C-reactive protein measurement in cerebro-spinal fluid.

C-Reactive protein (CRP) has been measured in 90 consecutive CSF specimens using both latex agglutination and an immunoradiometric assay (IRMA). In the 60 CSF specimens otherwise normal by standard biochemical and microbiological criteria, the median CRP level was 32 micrograms/l (95% confidence limits, 0-108 micrograms/l) and in the remaining abnormal specimens the median level was 176 micrograms/l (95% confidence limits, 110-325 micrograms/l, p = 0.001). C-Reactive protein was detected by a commercial latex agglutination kit at a level of approximately 120 micrograms/l and all significant CNS bacterial infections were positive (7 bacterial meningitis, 2 infected shunts). In addition, viral encephalitis, extensive intracranial malignancy and subarachnoid haemorrhage gave positive agglutinations, but not in every case. A further nine specimens with a minor elevation of CRP level were detected by IRMA (median 76 micrograms/l), but this was of little practical significance. We have shown that normal CSF C-reactive protein levels are very low and we conclude that latex agglutination set at a sensitivity of 120 micrograms/l, although only semi-quantitative, is a rapid and useful method to assess CSF C-reactive protein in routine clinical practice and, when positive, is strong supporting evidence for bacterial infection.

C-Reactive Protein↗
PubMed1985

Oxygen-derived free radicals promote hepatic injury in the rat.

We have investigated the possible protective effect of superoxide dismutase and allopurinol in a rat model of mild and severe hepatic necrosis produced by Corynebacterium parvum with or without endotoxin. Histology showed a sinusoidal mononuclear cell infiltrate with multiple granulomata but variable degrees of hepatic necrosis. In the severe hepatic injury model there was a reduction in mortality, associated with a decrease in histologic and biochemical evidence of hepatic necrosis, after treatment with superoxide dismutase. This protective effect was not demonstrated with partially heat-inactivated superoxide dismutase. In the mild hepatic injury model similar trends in reduction of serum levels of hepatic enzymes were observed after treatment with both superoxide dismutase and allopurinol. These results indicate that oxygen-derived free radicals may play an important role in the pathogenesis of hepatic injury in the rat.

Alanine Transaminase↗
PubMed1985

Drug influences on rat hepatic macrophage enzyme production and release in vitro.

Drug influences on hepatic macrophage enzyme release have been investigated using a rat model of macrophage recruitment and activation. N-acetyl-glucosaminidase (NAG), a lysosomal enzyme, and plasminogen activator (PA), a cytosolic enzyme, have been measured in both cell lysates and supernatants after 24 h in culture. 6-mercaptopurine (6-MP) and azathioprine significantly decreased (P less than 0.03) the enhanced production of NAG by recruited macrophages following stimulation in vitro (total NAG activity, nmol substrate hydrolysed/microgram cell protein; recruited macrophages exposed to endotoxin, no drug exposure 0.63 +/- 0.08, azathioprine 0.44 +/- 0.08, 6MP 0.36 +/- 0.06). Prednisolone, azathioprine and 6MP significantly reduced (P less than 0.05) the supernatant release of PA in response to endotoxin exposure in vitro by both cell types (supernatant PA values after 24 h in culture, recruited macrophages exposed to endotoxin, no drug 26.0 +/- 2.9 units, prednisolone 18.5 +/- 1.7 units, levamisole 27.3 +/- 4.7 units, azathioprine 18.1 +/- 2.3 units, 6MP 17.3 +/- 1.5 units). The results from this study indicate that certain drugs used in human liver disease are able to modify the secretory activity of rat hepatic macrophages.

Acetylglucosaminidase↗
PubMed1985

Pharmacology of propranolol in patients with cirrhosis and portal hypertension.

Ten patients with cirrhosis and protal hypertension received an initial 20 mg oral test dose of propranolol and subsequently 160 mg of a slow release preparation, orally, each day for seven days. Protein binding, serial plasma propranolol concentrations and effects on heart rate were studied. Protein binding was slightly reduced (mean 85%, range 78.9-88.1%) compared with four normals (mean 87.9%). In patients with severe liver disease (serum albumin less than 30 g/l) propranolol remained detectable in plasma 24 hours after the single 20 mg dose and high steady state concentrations (mean 266.5 ng/ml, range 84-406) were observed during regular dosing. At steady state there was a significant correlation between log total plasma propranolol concentrations and the percentage fall in heart rate (r = 0.659, p less than 0.05). We suggest that in patients with severe liver chronic disease (serum albumin less than 30 g/l), propranolol therapy should be initiated in hospital. The starting dose should be low (20 mg of the conventional formulation tds or 80 mg of the slow release preparation daily) and that regular monitoring of the heart rate should be carried out.

Aged↗
PubMed1984

Monocyte lysosomal enzyme release in response to naturally occurring circulating immune complexes.

To investigate the influence of naturally occurring immune complexes (ICs) on monocyte lysosomal enzyme release, blood monocytes have been isolated from normal human volunteers, purified, and maintained in culture for 5 days. These cells have been exposed in vitro to sera containing ICs and to the same sera depleted of ICs with 2% polyethylene glycol (PEG). IC-containing sera have been shown to result in increased lysosomal enzyme release (N-acetyl-beta-glucosaminidase (NAG) and beta-glucuronidase) sustained for up to 5 days even after brief (24-h) exposure (NAG activity at 120 h, nmol substrate hydrolysed ml-1 culture supernatant: control, 98 +/- 27; 2% PEG control, 70 +/- 10; IC serum exposure for 120 h, 305 +/- 73; IC serum exposure for 24 h, 330 +/- 95; exposure to IC-depleted sera 120 h, 158 +/- 93). Further analysis showed no relationship between the total IC concentration and enzyme release, nor was there any relationship between the complement component (C3) composition of the complexes and degree of enzyme release. These results confirm the potential importance of circulating IC on monocyte activation in man and indicate that this could result in changes in macrophage activity at the sites of inflammation.

Acetylglucosaminidase↗
PubMed1984

An evaluation of the one-day NBT-PABA/14C-PABA in the assessment of pancreatic exocrine insufficiency.

The one-day NBT-PABA/14C-PABA has been performed on 58 consecutive subjects with suspected or established pancreatic disease. 23 of these were normal subjects, 12 were subsequently shown to have other gastrointestinal disease and 23 had proven pancreatic disease. A PABA excretion index (PEI) has been calculated and, using our lower limit of normality (0.61), the test has shown an overall sensitivity of 83% and specificity of 89%. False positives were a particular problem in the other gastrointestinal disease group (25%). There was a close correlation between PEI and Lundh mean tryptic activity (r = 0.89). These results indicate that this test is a satisfactory screening test for pancreatic exocrine disease and is easier to perform with less likelihood of error than many other non-invasive tests of pancreatic function.

4-Aminobenzoic Acid↗
PubMed1984

Influence of naturally occurring human immune complexes on monocyte movement in vitro.

The influence of naturally occurring immune complexes (IC) on monocyte motility has been investigated. Both chemokinesis and chemotaxis have been measured, using modified Boyden chambers, in response to sera containing IC and to the same sera depleted of IC with 2% polyethylene glycol. Chemokinetic activity was markedly increased in the presence of IC-containing sera, and this increased activity was largely abolished, following IC depletion. The chemotactic activity of the IC-containing sera was largely independent of the IC content, since IC depletion only resulted in a modest decrease in stimulated movement. The chemotactic response to a standard chemoattractant (zymosan-treated sera) was significantly increased with the cells in the presence of IC-containing sera, and this effect was abolished following IC depletion. There was no relationship between the total IC concentration and changes in monocyte movement. These results indicate that circulating IC may markedly alter monocyte locomotion in such a way that more cells may be attracted more rapidly to an inflammatory focus.

Antigen-Antibody Complex↗
PubMed1983

Failure to demonstrate altered gastric emptying in irritable bowel syndrome.

In irritable bowel syndrome (IBS), abnormalities of motility have been observed in the esophagus and small bowel, as well as in the colon. In order to investigate gastric function, gastric emptying has been measured in 25 patients with strictly defined IBS and compared with 25 age- and sex-matched controls. A standard radioisotope method for measuring gastric emptying has been employed. There was no significant difference between the two groups (T1/2 gastric emptying, IBS subjects 99.3 +/- 9.4 min, control subjects 104.0 +/- 11.9 min, mean +/- SEM), nor was there any major correlation between different symptom patterns and altered gastric emptying times. The results of the present investigation suggest that future studies on abnormalities in IBS should investigate other aspects of gastric motor function.

Adult↗
PubMed1983

The influence of endotoxin in vitro on hepatic macrophage lysosomal enzyme release in different rat models of hepatic injury.

Since bacterial endotoxin is known to be involved in the pathogenesis of hepatic injury, the influence of endotoxin on lysosomal enzyme production by hepatic macrophages has been investigated. Macrophages have been isolated from the livers of normal rats, from the livers of rats given stilboestrol subcutaneously 4 days previously and from the livers of rats given Corynebacterium parvum intravenously 6 days previously. Following isolation and overnight culture, the macrophages have been maintained in in vitro culture for a further 24 h and the production of N-acetyl-beta-glucosaminidase (NAG) has been measured. Histological assessment has shown that in stilboestrol model an approximate doubling of sinusoidal cell numbers occurs and in the C. parvum model a heavy mononuclear cell infiltrate is present, together with granuloma formation. These changes are reflected in the numbers of macrophages isolated from the respective models. Levels of NAG production by resident macrophages from normal livers are low (0.25 +/- 0.05 nmol substrate hydrolysed/microgram cell protein/h) and unchanged following endotoxin exposure (0.25 +/- 0.05 units). Macrophages isolated from the stilboestrol model show levels of NAG production similar to normal (0.34 +/- 0.06 units), but this increases significantly following exposure to endotoxin (0.42 +/- 0.07 units). Macrophages from the C. parvum model demonstrate markedly enhanced production (0.61 +/- 0.09 units), but this does not increase significantly following endotoxin exposure (0.65 +/- 0.09 units). In contrast to macrophages from normal rat livers, macrophages recently recruited in the stilboestrol model demonstrate enhanced lysosomal enzyme production following endotoxin exposure. It is suggested that endotoxin, as well as other mediators of macrophage activation, may promote hepatic damage through this influence on newly recruited macrophages.

Acetylglucosaminidase↗
PubMed1982

Activation of monocytes by portal serum and its relationship to immunoglobulin, immune complex and endotoxin content.

To investigate the possibility that a "spillover effect" of substances from the portal vein into the systemic circulation accounts for the abnormal monocyte function in patients with liver disease, we have incubated human peripheral blood monocytes with paired specimens of portal and systemic serum from humans and rabbits. Monocytes incubated with portal serum released more of a lysosomal enzyme, N-acetyl-B-glucosaminidase, than those incubated with systemic serum (p less than 0.05). In order to delineate the factors responsible for this increased activity, the content of immune complexes, immunoglobulins and endotoxin in the paired specimens of portal and systemic serum was measured. Endotoxin was found in none of 16 human specimens of portal blood and five of the 16 rabbit specimens. Modestly increased levels of immune complexes, particularly of the IgG class, were found in the portal serum compared to the systemic serum (p less than 0.01). Corresponding studies on immunoglobulins showed a higher concentration of IgA in portal serum (p less than 0.05), but no difference in other classes of immunoglobulins or complement levels. There was good correlation between the enzyme production by monocytes and the concentration of immune complexes, particularly IgA (r = 0.687, p less than 0.001), but there was no relationship to the presence or absence of endotoxin. This evidence suggests that portal serum contains substances, particularly immune complexes, which under normal circumstances are sequestered by the liver. These are capable of "activating" monocytes in vitro and may play a role in the pathogenesis of certain types of liver disease.

Acetylglucosaminidase↗
PubMed1982

The incidence of occult thyroid disease associated with thyroid antibodies identified on routine autoantibody screening.

The presence of thyroid microsomal and/or thyroglobulin antibodies has been recorded over a 2 year period of 15 000 consecutive autoimmune profile request. Where there had been no initial clinical suspicion of thyroid diseases, 332 requests showed positive thyroid antibodies, and of these 63 (19%) had abnormal in vitro thyroid function tests (TFT). No differences were observed between the abnormal and normal groups with respect to the presence of different autoantibodies or to the age and sex distributions. Of these subjects with clinically unsuspected hypothyroidism but with abnormal TFTs, 29% were commenced on thyroxine therapy and experienced a symptomatic improvement, 25% remain well on no therapy and 9% continue on no treatment but with symptoms possibly attributable to hypothyroidism. 3% became clinically hypothyroid during a follow-up period of 2 years. 5% died of unrelated causes and there was inadequate follow-up information on the remainder. This study provides further confirmation that when thyroid antibodies, and in particular thyroid microsomal antibody, are found unexpectedly, a significant proportion of patients will have biochemical evidence of hypothyroidism and may benefit from appropriate treatment.

Autoantibodies↗
PubMed1981

Serum prednisolone levels in Crohn's disease and coeliac disease following oral prednisolone administration.

Serum prednisolone levels have been measured following the oral administration of 20 mg prednisolone in 10 normal subjects, in 9 patients with Crohn's disease and in 6 with coeliac disease. Serum prednisolone levels showed more variation in patients with Crohn's disease when compared to normal subjects. In those patients with Crohn's disease who failed to respond to corticosteroid therapy, adequate serum levels of prednisolone were achieved. Patients with coeliac disease had levels similar to normal. Serum protein binding of prednisolone was not significantly different between the groups. We conclude that, even in the presence of mucosal damage, patients with coeliac disease and Crohn's disease achieve therapeutic serum prednisolone levels.

Administration, Oral↗
PubMed1981

Monocyte function in Crohn's disease and ulcerative colitis.

Monocyte function as reflected by phagocytosis of Candida albicans and chemotaxis towards zymosan-activated serum has been assessed in Crohn's disease and ulcerative colitis. Phagocytosis and random movement were significantly increased to a similar degree in both diseases when compared with controls (p less than 0.001). There was no significant difference in chemotaxis between the disease and control groups, although there was a trend towards its being increased in ulcerative colitis. There was no correlation between the results obtained and disease activity or medication.

Adult↗
PubMed1981

The effect of plasma exchange on the in vitro monocyte function of patients with immune complex diseases.

In vitro function tests were performed on peripheral blood monocytes isolated from patients with putative immune complex diseases undergoing therapeutic plasma exchange. Bacterial killing by monocytes improved significantly after plasma exchange (pre: 29 +/- 5%; post: 39 +/- 3%). The intracellular content of the acid hydrolase N-acetylglucosaminidase (NAG) after in vitro culture rose significantly following plasma exchange (pre: 48.3 +/- 21 nmol mg protein-1 hr-1; post: 76.6 +/- 30.6), although the amount of NAG released into the supernatant was unchanged. Plasma exchange also resulted in reduced levels of immune complexes (IC) and clinical improvement in most patients. The beneficial effect of plasma exchange in patients with IC diseases may be partly due to removal of IC which are known to influence the functional activity of cells of the mononuclear macrophage series.

Acetylglucosaminidase↗
PubMed1981

A comparative study of lysosomal enzyme activity in monocytes and Kupffer cells isolated simultaneously in a rat model of liver injury.

Macrophages have been isolated and cultured in vitro from normal rat livers and from livers into which macrophages have been recruited in vivo, following an intravenous injection of killed Corynebacterium parvum. Simultaneously, peripheral blood monocytes have been isolated and cultured in vitro. After 24 hr in culture, supernatants and cell lysates were harvested and the activity of a lysosomal enzyme, N-acetyl-glucosaminidase (NAG), measured. NAG activity in the cell lysates of the recruited tissue macrophages was significantly higher than that measured in control tissue macrophages. Increased NAG activity was also observed in the supernatants from the recruited macrophages. In contrast, the NAG activity in cell lysates and supernatants of peripheral monocytes was not significantly changed after C. parvum injection. In this animal model, measurement of a lysosomal enzyme produced by peripheral monocytes did not reflect the magnitude of the changes observed for the tissue macrophages.

Acetylglucosaminidase↗
PubMed1980

Effect of long-term corticosteroid therapy on monocyte chemotaxis in man.

The influence of prednisolone on monocyte chemotactic activity in vitro at prednisolone concentrations comparable with those achieved in man following oral dosage has been investigated. Chemotactic activity of monocytes from each of sixteen normal subjects was suppressed by concentrations of prednisolone as low as 25 ng/ml (suppression of chemotaxis, 20%). Maximal suppression occurred at 100 ng/ml (suppression of chemotaxis, 48%) and no significant increase in suppression was produced by increasing the concentration to 200 ng/ml (suppression of chemotaxis, 53%). In contrast, monocytes isolated from ten patients receiving corticosteroid therapy showed no significant suppression of chemotactic activity when exposed to these concentrations of prednisolone, even though they exhibited a normal ability to respond to a chemotactic stimulus. The lack of suppression of monocyte chemotaxis in patients receiving corticosteroid therapy is unexplained, but may represent a change in the circulating monocyte or lymphocyte populations.

Administration, Oral↗