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Biomedical subjects

G M Hall

Publications and source records attributed to G M Hall.

At least 91 records · Page 5Linked to original sources
PubMed1994

Growth hormone suppression and glutamine flux associated with cardiac surgery.

Pharmacological doses of growth hormone (GH) in humans and rats increase plasma and muscle glutamine values. As major surgery results in a physiological rise in serum GH concentration, we investigated whether this physiological increase in GH altered glutamine metabolism. Eighteen patients undergoing coronary artery bypass graft (CABG) surgery were randomly assigned to receive somatostatin, 100 micrograms subcutaneously at induction of anaesthesia and 8 hourly for 48 h, or placebo. Somatostatin effectively blocked the physiological surge of GH following injury but did not affect plasma or muscle glutamine concentrations, which fell significantly in both groups. Plasma glutamine decreased by 31% (P < 0.01) and 28% (P < 0.01) in the control and somatostatin groups respectively. Muscle glutamine was reduced 45% (P < 0.001) in the control group and 50% (P < 0.001) in the somatostatin group. There was no difference in muscle or circulating glutamate, alanine or branched chain amino acid concentrations or in metabolite values between the somatostatin-treated patients and the control group. There was no relationship between the GH response to surgery and glutamine metabolism following major surgery.

Blood Glucose↗
PubMed1994

A randomised controlled trial of the effect of hormone replacement therapy on disease activity in postmenopausal rheumatoid arthritis.

OBJECTIVE: To assess the effects of hormone replacement therapy (HRT) on disease activity in postmenopausal rheumatoid arthritis (RA). METHODS: Two hundred postmenopausal outpatients (aged 45-65 years) were admitted into a single blind randomised placebo controlled trial of transdermal oestradiol (50 micrograms daily) over six months. Patients continued with routine antirheumatic medications. Compliance with HRT was monitored using serum oestradiol (E2) levels. Disease activity was monitored at entry, three and six months using erythrocyte sedimentation rate (ESR), articular index (AI), visual analogue pain scale (VPS) and early morning stiffness (EMS). RESULTS: Ninety one and 77 patients completed six months treatment with placebo and HRT respectively. There were no significant differences in baseline characteristics between the groups and no overall effects of treatment. However, 35 patients (41.6%), who completed HRT, failed to achieve serum E2 levels > 100 pmol/l at either three or six months and were considered 'poor-compliers'. In the remaining HRT 'compliers' (58.4%) there were significant improvements after six months in articular index (28.9%; p < 0.01) and pain score (21.7%; p < 0.05) compared with placebo, as well as reductions in ESR (8.9%; NS) and morning stiffness (25.2%; NS). Comparisons between HRT 'compliers' and 'poor-compliers' confirmed significant improvements in articular index (p < 0.001), pain score (p < 0.05) and morning stiffness (p < 0.001) in the 'compliers'. CONCLUSIONS: This study did not show an overall effect of HRT on disease activity when used as an adjunct therapy in postmenopausal patients. A subgroup of patients, who had greater increments in serum E2 whilst taking HRT, demonstrated improvements in some parameters of disease activity, suggesting a potential beneficial effect with good compliance and higher dose HRT. Most importantly, in the treatment of RA associated bone loss, HRT can be prescribed without fear of a disease flare up.

Aged↗
PubMed1993

The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women.

OBJECTIVE: To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of corticosteroids. METHODS: One hundred ninety-five postmenopausal patients with RA were compared with 597 post-menopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x-ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex-users (18%). RESULTS: Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval [95% CI] 3.4-10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0-13.0%) and by 7.4% at the hip (95% CI 1.2-13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex-user and never user groups. Results were confirmed in 54 patients who had whole-body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = -0.23, P < 0.01; whole-body BMD r = -0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = -0.32, P < 0.01; whole-body BMD r = -0.72, P < 0.01). CONCLUSION: Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low-dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.

Absorptiometry, Photon↗
PubMed1993

Increased levels of urinary collagen crosslinks in females with rheumatoid arthritis.

Bone loss is a feature of RA, but the exact mechanisms involved are not clear. The collagen crosslinks deoxypyridinoline (DPYR) and pyridinoline (PYR) are specific indices of 'mature' collagen breakdown and reflect increased bone turnover. The aims of the study were to examine crosslink levels in RA and their association with disease activity and the effect of steroids. Urinary crosslinks corrected for creatinine were measured on morning fasting samples by HPLC in 70 postmenopausal women with rheumatoid arthritis (RA) aged 45-65 and compared with 169 postmenopausal healthy age-matched controls from the population. Mean levels of PYR were significantly higher in RA cases than in controls (52.4 versus 37.5 nmols/mmolCr) although mean levels of DPYR did not differ significantly. A weak correlation was found with ESR and PYR (r = 0.35) but not with other markers of disease activity. Thirteen of the RA cases were current steroid users and their levels of DPYR and PYR even with low doses, were significantly elevated above those of non-users, ex-users and controls. The finding of raised urinary PYR but not the bone specific DPYR in nonsteroid using RA cases suggests that the increased collagen breakdown does not primarily come from bone but from other sources such as cartilage and synovium. The large increases in collagen excretion in low dose steroid users, may reflect the higher risk of osteoporosis in this group.

Aged↗
PubMed1993

Growth hormone secretion in response to surgery. Effects of cholinergic blockade and octreotide.

Cholinergic blockade markedly reduces the growth hormone (GH) response to most stimuli, with the exception of insulin induced hypoglycaemia. We have administered the cholinergic antagonist, atropine, known to cross the blood brain barrier, to eight healthy female patients prior to elective surgery in order to investigate the role of cholinergic pathways in the GH response to surgery. Additionally, eight patients received the octapeptide analogue of somatostatin, octreotide, known to suppress GH secretion. A control group matched for age and weight received no injection. The GH response to surgery was assessed by peak values and areas under curves. Octreotide resulted in a significant inhibition of GH secretion compared with the control group (p < 0.01 for both parameters). In contrast, atropine did not significantly inhibit the GH response to surgery. In conclusion, octreotide completely suppressed GH secretion during surgery, whereas cholinergic blockade was ineffective. Thus surgery is similar to insulin induced hypoglycaemia poglycaemia in that the GH response is not decreased by cholinergic blockade.

Adult↗
PubMed1993

The metabolic and hormonal response to cataract surgery. A comparison between retrobulbar and peribulbar blockade.

We studied the metabolic and hormonal responses of 30 elderly patients undergoing routine cataract surgery who were allocated randomly to receive either general anaesthesia, or local anaesthesia by means of either retrobulbar or peribulbar blockade. Both forms of local anaesthesia successfully prevented the increases in circulating cortisol and glucose concentrations seen in those patients who received general anaesthesia, there being no significant differences between retrobulbar and peribulbar blockade. The results show that the newer, and now more commonly performed peribulbar block, confers the same metabolic and hormonal stability as seen with the more traditional retrobulbar block.

Aged↗
PubMed1993

Depressed levels of dehydroepiandrosterone sulphate in postmenopausal women with rheumatoid arthritis but no relation with axial bone density.

The sex hormones dehydroepiandrosterone sulphate (DHEAS), oestradiol, and sex hormone binding globulin (SHBG) were measured in 185 postmenopausal women (aged 45-65 years) with rheumatoid arthritis (RA) and related to assessments of bone mineral density at the spine and proximal femur. Compared with 518 postmenopausal control women (aged 45-65 years), DHEAS levels were below normal in the 120 patients with RA who had never taken corticosteroids and levels were further depressed in 39 patients currently using steroids. Twenty six patients who had completed steroid treatment also had lower DHEAS levels, suggesting a delayed recovery of adrenal androgen secretion. Oestradiol and SHBG levels were similar in all groups. There was no correlation between sex hormones and disease activity. Oestradiol correlated with bone mineral density at all sites. Although oestradiol correlated with DHEAS, there was no relation between DHEAS and bone mineral density. The cause of below normal levels of DHEAS in RA is unclear, whether a consequence of chronic illness, immune dysfunction, or a defect of adrenal androgen synthesis.

Aged↗
PubMed1992

Granulocyte margination in the human lung and its response to strenuous exercise.

1. It is widely believed that the lung is an important site of granulocyte margination and releases most of the granulocytes of the peripheral neutrophilia of exercise. 2. We measured granulocyte margination in the lung in terms of the lung total blood granulocyte pool and the lung circulating granulocyte pool in eight patients without inflammatory disease or evidence of lung pathology by comparing the regional gamma-camera lung count rate of 111In-labelled granulocytes with that of 111In-labelled erythrocytes. According to the respective 111In activities in peripheral blood samples taken between 5 and 40 min after granulocyte injection, the lung marginating granulocyte pool was 0.78 (SEM 0.045) of the lung total blood granulocyte pool or 4.6 (0.92) of the lung circulating granulocyte pool 5 min after injection, decreasing to plateau values of 0.57 (0.053) and 1.53 (0.28) from 20 min after injection. This compared with corresponding whole-body ratios of about 0.6 and 1.5, respectively. 3. After 4 min of maximal exercise in four normal subjects given 111In-labelled granulocytes 60 min before exercise, the 111In-labelled granulocyte count rate over the lung increased to 1.23 (0.05) of the pre-exercise value with a time course that was essentially identical with the time course of the peripheral native neutrophilia. The spleen 111In signal decreased with the same time course, reaching a minimum of 0.63 (0.05) of the pre-exercise level at 5-10 min after the end of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intrasplenic blood cell kinetics in man before and after brief maximal exercise.

1. After a 4 min period of maximal exercise in 10 normal subjects (14 studies), there was a consistent decrease in total blood volume and a consistent increase in erythrocyte indices, which were maximal immediately after exercise. Peripheral platelet and leucocyte counts increased, but did not reach maximal values until 5-10 min after the end of exercise. 2. The distributions of 99mTc-labelled erythrocytes (five studies), 111In-labelled platelets (five studies) and 111In-labelled granulocytes (four studies) were monitored with a gamma-camera immediately after injection and before and after maximal exercise performed 60 min after injection. 3. Labelled erythrocytes equilibrated rapidly between the spleen and circulating blood after injection, whereas labelled platelets and granulocytes equilibrated more slowly. After exercise, each cell type was released from the spleen with a time course that was the reciprocal of the time course of the corresponding cell count in peripheral blood. Thus, whereas the radioactivity of 99mTc-labelled erythrocytes in the spleen, which fell to 0.46 (SD 0.09) of the pre-exercise value, increased towards its baseline value as soon as exercise was completed, the radioactivities of 111In-labelled platelets and 111In-labelled granulocytes decreased, to respective minimum values of 0.61 (0.09) and 0.63 (0.09) of the pre-exercise levels, 5-10 min after the end of exercise. The exercise-induced changes in lung radioactivity for each cell type, and their time courses, broadly reflected those in the corresponding cell counts in peripheral blood. Liver radioactivity tended to decrease for each cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.

Acute-Phase Reaction↗
PubMed1992

The effects of gender and sex hormones on outcome in rheumatoid arthritis.

Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome. Men, however, are more likely than women to die from extra-articular complications of rheumatoid disease. This chapter discusses the outcome and mortality studies that substantiate these conclusions and then examines the possible mechanisms that may account for them, including the HLA system, seropositivity, compliance, response to therapy and pain threshold. In particular, sex and sex hormones emerge as independent risk factors in rheumatoid disease. The epidemiological evidence points towards a peak age of onset of RA at the time of the menopause in women and towards later in life in men. Premenopausal women may fare better than postmenopausal women with RA. The possible protective effects of the oral contraceptive pill and the dramatic amelioration with pregnancy are well documented. In vivo and in vitro studies have demonstrated that sex hormones interfere with a number of the putative processes involved in the pathogenesis of RA, including immunoregulation, interaction with inflammatory mediators and the cytokine system, and direct effects on cartilage itself. All these observations point towards the importance of gonadal hormones. However, trials on the potential therapeutic use of sex hormones in RA are limited and, as yet, disappointing. Further work is necessary to determine whether the roles of sex hormones are as central protagonists or just supporting cast in the complex arena of rheumatoid disease.

Age Factors↗
PubMed1991

Rheumatoid nodules do not predict response to treatment with slow-acting anti-rheumatic drugs.

Rheumatoid nodules have been associated with a poor long-term prognosis. We investigated whether they predict a poor response to treatment with slow-acting anti-rheumatic drugs (SAARDs). Two hundred and twenty-eight patients with rheumatoid arthritis (RA) were treated for six months with a SAARD. Clinical and laboratory assessments of disease activity were made initially and after 6 months' treatment. Patients were divided into two groups according to the presence or absence of nodules at entry. Twenty-one % had nodules before treatment but their response was no different to patients without nodules (79%), both groups showing improvements in all variables. Males were more likely to develop nodules and had a relative risk of 1.7. High titres of rheumatoid factor correlated with nodules and no sero-negative patients had nodules. We conclude that nodules are not predictive of poor response to treatment with a SAARD, despite their presence being associated with a poor long-term prognosis. One possible implication is that SAARDs themselves, despite an early response, may not effect long-term outcome.

Anti-Inflammatory Agents↗