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Biomedical subjects

G Husby

Publications and source records attributed to G Husby.

At least 163 records · Page 9Linked to original sources

Piroxicam and naproxen plasma concentrations in patients with osteoarthritis: relation to age, sex, efficacy and adverse events.

Piroxicam and naproxen plasma concentrations were obtained after 4 weeks active therapy between 3 and 12 hours post-dose in 640 and 629 patients, respectively. These patients are a subset of 2,035 patients with osteoarthritis on whom we have reported previously (11) in a double-blind multicentre safety and efficacy trial comparing piroxicam 20 mg/day and naproxen 750 mg/day. The purpose of the present study was to look for an association of plasma drug concentration with the variables of: age, sex, adverse events and efficacy. There was a statistically significant increase in plasma concentrations of both drugs with increasing age and females had higher concentrations than males. The increase in plasma concentration seen with increasing age was of a magnitude of 25% for piroxicam and 20% for naproxen when comparing a 50 year old to an 80 year old. However, less than 15% of the variability in plasma concentrations seen between patients is accounted for by age and sex. Within the plasma concentrations achieved with these doses, no association with adverse events, non-serious or serious, and efficacy was noted.

Age Factors↗

Absence of interferons-alpha and -gamma in renal lesions of systemic lupus erythematosus and membranous glomerulonephritis.

Frozen kidney biopsy sections from nine patients with systemic lupus erythematosus (SLE) as well as many other renal diseases, including IgA nephropathy, membranous nephritis, and minimal change nephrotic syndrome, were negative for interferons -alpha and -gamma by immunofluorescence. Lupus patients studied included several subjects with marked serum elevations of interferon activity as well as others with low or negative serum interferon levels. Isolated glomerular eluates prepared from normal and SLE kidneys showed no functional interferon activity by virus plaque inhibition assay. Components of normal as well as SLE serum showed no direct binding to interferon -alpha or -gamma by ELISA assays.

Arthritis, Rheumatoid↗

Serum amyloid A protein in acute myocardial infarction.

Tissue injury including myocardial infarction leads to a variety of changes in plasma proteins commonly referred to as "the acute phase response". In this report the concentrations of serum amyloid A protein (SAA) were measured serially in 6 patients with myocardial infarction and 4 with angina. SAA was found to be increased in all patients with infarction, but in no patients with angina. Significantly increased SAA levels were detected 12 hours after the peak level of creatine kinase, and the concentrations of SAA seemed to correlate to the amount of damaged tissue. The SAA-response was both faster and more extensive than the response of C-reactive protein (CRP), but the correlation between SAA and CRP was very good.

Aspartate Aminotransferases↗

Characterization of amyloid protein AA and its serum precursor SAA in the horse.

Amyloid was extracted from the liver of a horse that had developed amyloidosis after being used for several years for the production of antibodies to bacterial antigens. The amyloid fibrils were shown to be of the AA type. Two AA proteins with molecular weights of 9000 and 11,000 and with identical partial N-terminal amino acid sequences were identified. Marked structural homology with AA from other species including man was seen, although clear species-related antigenic specificity was observed. SAA isolated from an acute phase (septic abortion) horse serum was identical to AA with respect to antigenicity and the 10 first N-terminal amino acid residues that have been studied up to now. The bulk of SAA was present in the high-density lipoprotein complex in serum. Also SAA was heterogeneous with respect to size, most molecules having a molecular weight of 11,000, and a minority 9000.

Amino Acid Sequence↗

Gastrointestinal peptides in serum and synovial fluid from patients with inflammatory joint disease.

The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders.

Adult↗

Serum amyloid protein A (SAA): an indicator of inflammation in AIDS and AIDS-related complex (ARC).

The acute phase protein serum amyloid A (SAA) and C-reactive protein (CRP) were measured in a group of 30 homo- and bisexual males with AIDS, 31 males with AIDS-related complex (ARC) and 23 healthy male homosexual controls (HC) in Copenhagen. The mean values of SAA and CRP were significantly higher in the AIDS group compared to the two other groups. SAA was elevated also in the ARC group, whereas the mean CRP value was normal. No increase in SAA and CRP was found in the HC group. The AIDS patients with Pneumocystis carinii infections had the highest SAA values, those with Kaposi's sarcoma the lowest. The elevations in SAA and CRP preceded episodes of acute opportunistic infections often by several days before the infectious agents were identified. We conclude that patients with AIDS are able to establish an acute phase response as reflected by elevated SAA and CRP, and that measurement of these proteins may be of diagnostic and prognostic value.

AIDS-Related Complex↗

The effect of normal and rheumatic pregnancy sera on intracellular cathepsin B activity in human monocytes.

In a prospective study of pregnant patients with rheumatic disease and healthy pregnant women, the effect of pregnancy serum on human blood monocytes was investigated. Intracellular activity of the collagen degrading enzyme cathepsin B was found to be significantly depressed in monocyte cultures exposed to pregnancy and cord sera, independent of the presence or absence of an inflammatory state in the pregnant woman. Enzyme inhibition developed in a dose-dependent fashion over 3 days in culture. In contrast to cord and pregnancy sera, non-pregnant serum and serum from oral contraceptive users displayed enzyme stimulating activity. The response of monocytes to the stimulating agent carrageenan was unaffected by inhibitory sera. The nature of possible inhibitory factors in pregnancy and cord serum is discussed.

Adolescent↗

Immunohistochemical studies of interleukin-2 and gamma-interferon in rheumatoid arthritis.

Synovial tissues were studied, using immunofluorescence techniques, for localization of lymphocytic infiltrates and immune reactants, including C3, C5b-9, C9, and Ia antigen. Tissue distribution of interleukin-2 (IL-2) and gamma-interferon was also determined, using mouse monoclonal antibodies. IL-2 was found in association with OKT8 and OKT4 T cells, and gamma-interferon was noted in association with T cells, B cells, and macrophages. Staining both for IL-2 and for gamma-interferon was surprisingly faint in view of the intensity of lymphocytic infiltration.

Arthritis, Rheumatoid↗

Amyloid 'degrading factor activity': a non-specific calcium-mediated effect.

The clarification of turbid AA-amyloid-fibril-containing agarose gels by serum has been ascribed to degradation of the fibrils and designated as 'amyloid degrading factor'. In the present study, sera of 32 healthy blood donors and 32 patients with rheumatoid arthritis all showed 'degrading factor activity' against both AA amyloid fibrils and a non-fibrillar reticulin preparation of normal liver in an agarose plate assay. AL amyloid fibrils were not affected. The 'degrading activity' of serum was correlated with the serum albumin concentration, and the effect was also given by purified human and bovine serum albumin, although it was not seen with other serum proteins. The 'degrading activity' of serum against AA amyloid and reticulin was significantly correlated: both substrates showed low levels in a chronic disease such as rheumatoid arthritis, and reticulin inhibited 'degrading activity' against AA amyloid and vice versa. These results suggest the same process involves both substrates. 'Degrading activity' was also given by EDTA and a specific calcium chelator, and was inhibited by calcium and magnesium. An enzyme inhibitor showed only partial inhibition of the 'degrading activity' of serum, purified albumin, and EDTA. These results suggest that serum 'degrading factor activity' is a non-specific calcium-mediated effect against AA amyloid and reticulin preparations dispersed in agarose. It may represent a change in the degree of aggregation of these proteins rather than being an effect of proteolytic degradation. This confirms the conclusions of other workers that amyloid 'degrading factor activity' is an phenomenon in vitro of doubtful pathophysiological significance.

Amyloid↗

Transformation of amyloid precursor SAA to protein AA and incorporation in amyloid fibrils in vivo.

Experimental amyloidosis was induced in mice by intraperitoneal injections of endotoxin (lipopolysaccharide (LPS)). In addition to LPS, a group of mice received high-density lipoprotein (HDL)-SAA complexes isolated from human acute-phase serum, whereas a group of control mice received saline in addition to LPS. Isolated amyloid fibrils from the mice given HDL-SAA contained human AA protein, as shown by immunodiffusion, immunoblot, and enzyme-linked immunosorbent assay techniques, in addition to mouse AA. In contrast, amyloid from the control mice contained exclusively AA of mouse origin. Thus, the experiments provided solid evidence that SAA is the precursor for amyloid fibril protein AA.

Amyloid↗

Amyloid-related serum protein (SAA) during and after pregnancy in healthy women and women with rheumatic disease.

The usefulness of amyloid-related serum protein (SAA) as an indicator of disease activity has been evaluated in 11 patients with rheumatoid arthritis (RA), 2 patients with psoriatic arthritis (PA) and 13 patients with ankylosing spondylitis (AS) prospectively studied during and after pregnancy. For comparison, SAA levels were recorded serially during and after pregnancy in 28 healthy pregnant women. SAA levels were unaltered by gestation and thus within the normal range during normal pregnancy, but were raised in healthy pregnant women with episodes of intercurrent infections. In RA and AS patients, SAA concentrations correlated to disease activity during and after pregnancy. Serial levels of SAA and C-reactive protein in healthy women and patients paralleled each other with the most pronounced inflammatory response displayed by SAA. We conclude that SAA is a sensitive and reliable indicator of inflammatory events both in the pregnant and non-pregnant state.

Amyloid↗

Hyaluronic acid production in vitro by synovial lining cells from normal and rheumatoid joints.

Organ cultures and primary cell cultures were established from synovial tissue collected from patients with rheumatoid arthritis. Hyaluronic acid measured by the incorporation of [3H]glucosamine into the polysaccharide was found to be synthesised in the cultures immediately after transfer from in-vivo to in-vitro conditions. This was in contrast to the primary cultures established from cells isolated from normal joints. The latter cells did not synthesise any detectable hyaluronate. 90-100% of the cells in primary culture were found to be esterase positive, indicating their macrophage nature. The molecular weight of the hyaluronate produced by the pathological cells was low (approximately 50 000) compared with the molecular weight of hyaluronate found in joint fluid from normal or rheumatoid joints. Cell lines of fibroblasts established from rheumatoid joints and studied after four or seven passages also produced hyaluronate of low molecular weight. It is known that similar cell lines from normal joints produce a high molecular weight polymer.

Adult↗

Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromsø, northern Norway.

In an epidemiological survey in Tromsø, northern Norway a prevalence of definite ankylosing spondylitis (AS) of between 1.1% and 1.4% was found (males: 1.9-2.2% and females: 0.3-0.6%). The ratio of male to female was between 3.9 and 6.1 in favour of the male sex. It was calculated that 6.7% of the B27 positive individuals had AS, and that 22.5% of the B27 positive subjects with back pain or stiffness suffered from AS.

Adult↗

Spinal ankylosing spondylitis: a variant form of ankylosing spondylitis or a distinct disease entity?

In a population survey of ankylosing spondylitis (AS) seven subjects, six males and one female, had x-ray changes in the lumbar spine typical of AS but without concomitant roentgenological sacroiliitis. The overall prevalence of such cases in the population studied was 0.37%. Four out of these seven subjects carried the tissue antigen HLA-B27 (57%). The clinical and roentgenological features of these subjects are described and it is suggested that the x-ray findings represent a mild and variant form of primary or definite AS.

Adult↗