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Biomedical subjects

A J Griffin

Publications and source records attributed to A J Griffin.

At least 19 recordsLinked to original sources

Misleading results from immunoassays of serum free thyroxine in the presence of rheumatoid factor.

A novel interference with measurements of serum free thyroxine (FT4) caused by rheumatoid factor (RhF) is described. We found misleading, sometimes gross, increases of FT4 results in 5 clinically euthyroid elderly female patients with high RhF concentrations. All 5 patients had high FT4 on Abbott AxSYM or IMx analyzers. "NETRIA" immunoassays gave misleading results in 4 of the 5 patients; Amerlex-MAB in 2 of 4 patients; AutoDELFIA in 2 of the 5; and Corning ACS-180 and Bayer Diagnostics Immuno 1 in 1 of the 5. BM-ES700 system results for FT4 in these women remained within the reference range. Results for serum T4, thyroid-stimulating hormone, free triiodothyronine, thyroid-hormone-binding globulin, and FT4 measured by equilibrium dialysis were normal in all 5 patients. Drugs, albumin-binding variants, and anti-thyroid-hormone antibodies were excluded as interferences. Addition to normal serum of the RhF isolated from each of the 5 patients increased the apparent FT4 (Abbott AxSYM). Screening of 83 unselected patients demonstrated a highly significant positive correlation between FT4 (Abbott AxSYM) and RhF concentrations. Discrepant, apparently increased FT4 with a normal result for thyroid-stimulating hormone should lead to measurement of the patient's RhF concentration.

Aged↗

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↗

Indomethacin treatment in newborn canine endotoxic shock.

Prostaglandins have been reported to play an important role in endotoxic shock. However, the beneficial effects of prostaglandin synthesis inhibitors for the treatment of newborn endotoxic shock have been controversial. This study was performed to evaluate the effects of indomethacin on the hemodynamics during fulminant endotoxic shock in newborn dogs. After E. coli lipopolysaccharide (LPS) injection, mean arterial pressure was maintained for the first 60 min, and then declined from 53 +/- 2 to 27 +/- 2 mmHg at 120 min. Cardiac output dropped from 0.37 +/- 0.03 to 0.24 +/- 0.03 L/min/kg 5 min after LPS injection and continued to decline to 0.12 +/- 0.01 L/min/kg at 120 min. Indomethacin treatment 20 min prior to LPS injection attenuated the hypotension (50 +/- 3 mmHg at 120 min, p less than 0.05) and the decrease of cardiac output (0.18 +/- 0.02 L/min/kg at 120 min, p less than 0.05). Indomethacin treatment 5 min after LPS injection also attenuated the hypotension (55 +/- 4 mmHg at 120 min, p less than 0.05) and the decrease of cardiac output (0.21 +/- 0.02 L/min/kg at 120 min, p less than 0.05). Survival times were increased by the indomethacin treatments. Thus, indomethacin appears to be beneficial for the treatment of fulminant hemodynamic deterioration in newborn endotoxic shock.

Animals↗

Diltiazem treatment in newborn canine endotoxic shock.

The mortality of sepsis/septic shock continues to be high in newborns. However, there is no established method in its treatment. Although calcium channel blockers ameliorate the hemodynamic deterioration of adult circulatory shock, their effects on newborn endotoxic shock have not been elucidated. This study was performed in newborn dogs to investigate the effects of diltiazem on newborn endotoxic shock. Endotoxic shock was induced in newborn dogs (2-10 days old, 300-800 g) by an intravenous injection of E. coli lipopolysaccharide (LPS; 1.5 mg/kg), and diltiazem (DZ) at the dose of 300, 600 or 1200 micrograms/kg was administered intravenously 20 min prior to LPS injection. Hemodynamic changes were serially observed until 120 min after LPS injection. The heart rate, mean arterial pressure and cardiac output decreased after LPS injection, and systemic vascular resistance decreased. DZ at the dose of 600 micrograms/kg attenuated the decreases of MAP and cardiac output, but 300 and 1200 micrograms/kg of DZ exacerbated them. DZ at the dose of 1200 micrograms/kg decreased the heart rate, and DZ at all three doses attenuated the increase of systemic vascular resistance. Therefore, 600 micrograms/kg of DZ is beneficial in the treatment of endotoxic shock in newborn dogs.

Animals↗

Beta-adrenergic drug therapy in newborn canine endotoxic shock.

The mortality of septic shock remains high in newborns. Although the effectiveness of adrenergic drug therapy continues to be controversial, adrenergic drugs have been used for the treatment of newborn endotoxic shock. To elucidate the effects of beta-adrenergic drugs on the fulminant hemodynamic deterioration of newborn endotoxic shock, newborn dogs (2-10-day-old, 264-800 g) were given Escherichia coli lipopolysaccharide (LPS; 10 mg/kg iv) and treated with isoproterenol (0.1 micrograms/kg/min) or dopamine (5 micrograms/kg/min) infusion from 5 to 120 min after LPS injection. Isoproterenol attenuated the effects of LPS by increasing the mean arterial pressure (32 +/- 2 vs. 13 +/- 1 mmHg at 120 min), cardiac output (183 +/- 29 vs. 118 +/- 23 ml/min/kg at 120 min), and the survival time (5.3 vs 2.9 hr). However, dopamine did not improve the hemodynamic deterioration. As dopamine-beta-hydroxylase activity in the blood was significantly lower in newborn dogs than in adult dogs, inadequate response of newborn dogs to dopamine was thought to be in part due to enzymatic immaturity.

Adrenergic beta-Agonists↗

Endotoxin shock in newborn dogs: serial hemodynamic studies.

Using a newly modified dye dilution method for cardiac output determination, we successfully performed frequent serial hemodynamic measurements in newborn dogs to characterize hemodynamic changes in endotoxin shock in neonates. Sixty-seven mongrel newborn dogs (2 to 20 days old, 300 to 1500 gm) were divided into four groups: group 1 (2 to 20 days old, 300 to 1500 gm) received normal saline solution, group 2 (2 to 10 days old, 300 to 800 gm) received 1.5 mg/kg of Escherichia coli lipopolysaccharide (LPS), group 3 (2 to 10 days old, 300 to 800 gm) received 10 mg/kg of LPS, and group 4 (11 to 20 days old, 801 to 1500 gm) received 10 mg/kg of LPS. Cardiac output, heart rate, mean arterial pressure, systemic vascular resistance, and minute work were measured serially after endotoxin administration for 4 hours. Despite extensive manipulation, these measurements were stable in controls throughout the length of the study. Endotoxin, administered at two different doses of 1.5 mg/kg and 10 mg/kg, had profound effects on hemodynamic responses. These effects included a significant dose-related fall in cardiac output, minimal changes in heart rate, and a marked rise in systemic vascular resistance. The hemodynamic changes reported in this study lend additional support to the hypothesis that maturational factors are involved in the hemodynamic response to LPS.

Animals↗

Clinical sacroiliac tests in ankylosing spondylitis and other causes of low back pain--2 studies.

Independent assessment by 2 observers of 4 tests for sacroiliac (SI) pain in patients with either mechanical/degenerative low back pain (M/D LBP) or ankylosing spondylitis (AS) showed all 4 to be reproducible, but only 2 of them, namely, pressure over the anterior superior iliac spines and pressure over the lower half of the sacrum, gave worthwhile discrimination. Positive results in these 2 tests were significantly associated with definite AS but also with the combination of low back pain, the HLA B27 antigen, and normal or near normal radiographs, a condition we have called presumptive ankylosing spondylitis.

Adolescent↗

HLA DR antigens and disease expression in rheumatoid arthritis.

Ninety-four patients with rheumatoid arthritis who possessed one or more of the HLA DR alloantigens 2, 3, or 4 were studied to investigate the genetic influence on disease severity and prognosis. In those with a disease duration of less than 10 years radiological damage was less in patients with DR2 than in those without this antigen. When current joint scores were compared, patients with this antigen had less evidence of disease than patients with DR3 or 4, DR3 patients having the highest scores. The presence of nodules and Sjögren's syndrome were less common in the DR2 patients. Variability in response to disease modifying drugs according to the patient's HLA DR antigen status may explain these differences. It is concluded, however, that possession of HLA DR2 may be an indicator of good prognosis in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗

Disease activity and pregnancy associated alpha 2-glycoprotein in rheumatoid arthritis during pregnancy.

Fourteen patients with rheumatoid arthritis were studied during pregnancy and clinical disease activity and serum concentrations of pregnancy associated alpha 2-glycoprotein (PAG) measured at monthly intervals until parturition. Disease activity diminished during pregnancy in 10 patients (group 1) and increased or remained unchanged in four (group 2). The mean PAG concentration produced by group 1 was 1250 +/- 737 mg/1, which was significantly higher than the mean of 470 +/- 304 mg/1 produced by group 2. Furthermore, there was a highly significant negative correlation coefficient (r = -0.41; p less than 0.001) between disease activity and PAG concentrations during gestation. Since there was no significant difference between the two groups of patients in any of the other serum factors measured, and since PAG has immunosuppressive properties in vitro, the results suggest that this protein may play an important part in inducing the remissions of rheumatoid arthritis which frequently occur during pregnancy.

Arthritis, Rheumatoid↗