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Biomedical subjects

D A Brewerton

Publications and source records attributed to D A Brewerton.

At least 19 recordsLinked to original sources
PubMed1991

Increased calcitonin gene-related peptide (CGRP), substance P, and enkephalin immunoreactivities in dorsal spinal cord and loss of CGRP-immunoreactive motoneurons in arthritic rats depend on intact peripheral nerve supply.

The distribution of peptides thought to be involved in pain modulation--substance P, calcitonin gene-related peptide (CGRP), and enkephalin--were studied in the spinal cord and dorsal root ganglia of polyarthritic rats and in rats with one sciatic nerve sectioned prior to induction of arthritis. In arthritic rats there was a bilateral increase of CGRP- and substance P-immunoreactive fibers and appearance of enkephalin-immunoreactive cell bodies in the dorsal horn of the lumbar (L4) spinal cord when compared to controls. In the corresponding dorsal root ganglia there were significant increases of CGRP- (P less than 0.02) and substance P- (P less than 0.001) immunoreactive cell bodies compared to controls. In the ventral horn of the control rats CGRP-immunoreactive motoneurons were abundant but were significantly (P less than 0.001) reduced in the arthritic spinal cord. Less pronounced changes were seen in the contralateral L4 spinal cord of arthritic rats with unilateral sciatic nerve section. In the ipsilateral dorsal horn, however, CGRP- and substance P-immunoreactive fibers were markedly depleted, and no enkephalin cell bodies were present. Furthermore, a number of CGRP-immunoreactive motoneurons were observed. In the ipsilateral L4 ganglia CGRP- (P less than 0.02) and substance P- (P less than 0.02) immunoreactive cells were significantly decreased compared to the contralateral side. The data suggest that pain perception is linked to complex interactions between CGRP, substance P, and enkephalin in sensory pathways and an intact peripheral input. The loss of CGRP-immunoreactive motoneurons may reflect muscular dysfunction associated with the arthritic condition.

Animals↗
PubMed1991

Echocardiographic diastolic abnormalities of the left ventricle in inflammatory joint disease.

Echocardiographic early diastolic abnormalities have been shown recently in 50% of men with ankylosing spondylitis. Similar techniques were used to investigate subjects with rheumatoid arthritis and psoriatic arthritis with or without spondylitis. These subjects had no clinical, radiographic, or electrocardiographic evidence of cardiac or respiratory disease. Echocardiographic abnormalities seen resembled those of ankylosing spondylitis in that the interval between minimum left ventricular dimension and mitral valve opening was prolonged in 12 of 22 subjects with rheumatoid arthritis and in seven of 11 subjects with psoriatic arthritis. Isovolumic relaxation time was significantly prolonged in four subjects with rheumatoid arthritis and one with psoriatic arthritis. Unlike ankylosing spondylitis, however, there was consistent reduction in peak rate of left ventricular dimension increase in subjects with rheumatoid arthritis and psoriatic arthritis. In addition, the dimension increase during atrial systole was greater than normal in nine subjects with rheumatoid arthritis and two with psoriatic arthritis. The most likely cause of these abnormalities is increased connective tissue deposition in the myocardium.

Adult↗
PubMed1991

Regional distribution of mast cells and peptide containing nerves in normal and adjuvant arthritic rat synovium.

Simultaneous visualization of nerves and mast cells in the rat synovium was possible with double staining. Thus, a direct comparison could be made of nerves and mast cells in the ankle joints of healthy rats and in those with severe adjuvant induced polyarthritis. Nerves were studied with avidin-biotin-peroxidase complex (ABC) immunostaining, using heterologous antisera to protein gene product 9.5 (PGP 9.5), a recently discovered neural protein, and the neuropeptides substance P and calcitonin gene related peptide (CGRP). Mast cells were visualized by metachromatic staining of granule heparin. With double staining of sections, a parallel distribution of mast cells and nerves in all parts of the normal synovium was noted. In rats with adjuvant induced arthritis, a near total parallel disappearance of mast cells and nerves in the synovium occurred. In the arthritic rat such mast cell/nerve "units" were only present in the region where synovium attaches to bone. The observed regional depletion of both nerves and mast cells in arthritis may be of importance in the pathophysiology of arthritis.

Animals↗
PubMed1990

Introduction: B27-associated diseases.

As an introduction, a hypothesis for the causation of ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and rheumatoid arthritis is outlined. It comprises ten basic mechanisms. With that hypothesis as a background, a further ten issues based on clinical evidence are presented for discussion. Finally, four questions are presented on behalf of the clinicians.

Arthritis, Infectious↗
PubMed1990

Nerves in inflammatory synovium: immunohistochemical observations on the adjuvant arthritis rat model.

Previous evidence has been presented that neurogenic input may influence adjuvant induced arthritis (AA) in rats. We now present evidence of alterations in synovial nerves in AA. Nerves were studied in well perfused and fixed rats, using immunohistochemistry with the sensitive avidin-biotin peroxidase complex (ABC) method and heterologous antisera to cytoskeletal protein gene product 9.5 (PGP) and the neuropeptides substance P and calcitonin gene related peptide (CGRP). The innervation of synovium was compared in normal rats and rats with AA. Observations concordant with what has been reported for neuropeptide nerves in the synovium of patients with rheumatoid arthritis (RA) are presented. It has been suggested that neural peptide substances are reduced in nerves of synovium from patients with RA. In the AA rat a specific reduction of lining zone and sublining nerves in the synovium was noted. The AA rat model is very suitable for studying the involvement of synovial nerves in arthritis, permitting optimal preservation of immunoreactive neural epitopes.

Animals↗
PubMed1989

Polymorphonuclear leucocyte motility in men with ankylosing spondylitis.

The polymorphonuclear leucocyte (PMN) response to a chemotactic or chemokinetic stimulus is enhanced in men with ankylosing spondylitis (AS). This effect does not parallel the severity of disease activity or the size of the acute phase response, and it is independent of non-steroidal anti-inflammatory drug treatment. Polymorph function is normal in HLA-B27 positive brothers of probands with AS and in other HLA-B27 positive individuals in the absence of disease. Polymorph motility is also normal in patients with psoriasis vulgaris or Crohn's disease, indicating that enhanced PMN motility is not a non-specific consequence of all inflammatory disorders.

Adult↗
PubMed1988

The influence of nonsteroidal anti-inflammatory drugs and probenecid on the renal response to and kinetics of piretanide in man.

The mechanism by which nonsteroidal antiinflammatory drugs interfere with the action of loop diuretics is not clear. We studied the renal response to an acute challenge of piretanide superimposed on pretreatment with either placebo, probenecid, indomethacin, or piroxicam in seven maximally hydrated subjects. No change was seen in glomerular filtration rate, as measured by creatinine clearance, throughout the experiments. When compared with responses to piretanide challenge after placebo pretreatment, probenecid reduced by 65% the peak fractional excretion of sodium (FENa), with a corresponding reduction in diuretic excretion. Pretreatment with indomethacin reduced peak FENa by 35%, but urinary delivery of piretanide was not altered. In contrast, piroxicam did not influence FENa but significantly reduced the delivery of both sodium and piretanide into urine. We conclude that the activity of nonsteroidal antiinflammatory drugs within the renal tubule varies among individual drugs and cannot be explained solely by their common mechanism of antiinflammatory action.

Administration, Oral↗
PubMed1988

Effect of maximal hydration on the renal responses to pretreatment with nonsteroidal anti-inflammatory drugs and probenecid in man.

The renal response to a challenge of maximal water diuresis has been studied in seven subjects pretreated over 48 h with either placebo, probenecid, indomethacin or piroxicam. Probenecid did not alter the excretion of water and sodium chloride when compared with placebo responses, but increased both phosphate and urate clearances. Indomethacin reduced significantly both water and sodium chloride clearances by approximately 40%. Piroxicam reduced water excretion to a similar extent but did not influence salt output. In parallel with these changes, both drugs caused significant phosphaturia. It is concluded that the renal actions of nonsteroidal anti-inflammatory drugs (NSAIDs) are individually distinct and involve direct effects on tubular transport of ions and water to differing extents within both the proximal and distal portions of the nephron.

Adult↗
PubMed1988

Ankylosing spondylitis without B27: no evidence for gene conversion.

Isoelectric focusing gel electrophoresis was used to look for variant HLA molecules in five patients with HLA-B27 negative ankylosing spondylitis (AS). The isoelectric points of the HLA-A and B antigens from these patients and HLA paired controls were identical. This implies that the HLA-A and B antigens from the patients with AS and the controls are similar. Gene conversion of a nucleotide sequence from a B27 positive gene is thus unlikely to be the explanation for the existence of AS in patients who are HLA-B27 negative by alloantisera typing.

Female↗
PubMed1988

The arthropathy of cystic fibrosis.

Musculoskeletal symptoms are frequent in cystic fibrosis (CF). Here the clinical features of 29 patients with CF who had significant arthropathy are described. Twelve had episodic arthritis (EA) characterised by repeated short attacks of severe, incapacitating polyarthritis, which in seven was associated with fever and erythema nodosum. Ten patients had hypertrophic pulmonary osteoarthropathy (HPOA). The onset of symptoms in the group with HPOA was usually later (mean age 20 years v 16 years for EA) and was associated with significantly worse lung function than in patients with CF, either without arthropathy or with EA. Seven patients had arthropathies which could not be classified as EA or HPOA.

Adolescent↗
PubMed1987

The myocardium in ankylosing spondylitis. A clinical, echocardiographic, and histopathological study.

Cardiac function was investigated in men with ankylosing spondylitis (AS) age 21-65 years who had no cardiorespiratory symptoms or known abnormalities of heart or lungs. Chest radiographs and standard electrocardiograms were normal in 73 of 74 subjects. In echocardiographs of 30 men, left atrial size and left ventricular cavity size and wall thickness were normal. Minor abnormalities in the valve roots were present in 3 older men. Early diastolic abnormalities of the left ventricle were demonstrated in 16 of 30 subjects. This finding was confirmed by repetition of the echocardiography a year later in 15 subjects and by comparison of 11 probands with their healthy brothers. Myocardial tissue obtained at necropsy from 28 AS patients without ischaemic or valvular heart disease or hypertension was studied. A mild, diffuse increase of interstitial connective tissue was seen but there was no inflammatory change or amyloid. Computerised image analysis showed 30.7% interstitial reticulin compared with 17.7% in age/sex matched controls (p less than 0.0001).

Adult↗
PubMed1987

The effects of naproxen and sulindac on renal function and their interaction with hydrochlorothiazide and piretanide in man.

We have studied the effect of a single dose challenge of naproxen (500 mg) and sulindac (200 mg) on renal function in five volunteers, and the effect of a single dose challenge of the thiazide, hydrochlorothiazide (100 mg), and loop diuretic, piretanide (6 mg) on renal function when the diuretics were given alone or when superimposed on chronic therapy of either naproxen or sulindac. None of the nonsteroidal anti-inflammatory drug (NSAID) or diuretic exposures significantly influenced glomerular filtration rate, as measured by creatinine clearance. Over the first 4 h of the study, both naproxen and sulindac reduced fractional excretion of sodium by approximately 50%. Sulindac also caused a significant uricosuria whilst naproxen promoted urate retention. Similar changes were observed over 8 h. Superimposition of either hydrochlorothiazide or piretanide on top of chronic sulindac therapy resulted in a blunting of the natriuresis by approximately 30% compared to when these diuretics were given alone: the action of the diuretics was unchanged by naproxen. Sulindac pretreatment did not alter the urinary excretion of either hydrochlorothiazide or piretanide; naproxen did not alter hydrochlorothiazide excretion. On the basis of these findings, it is concluded that NSAIDs exert direct tubular effects that do not necessarily interfere with the delivery of diuretics to their sites of action within the nephron.

Adult↗
PubMed1987

Polymorphonuclear leukocyte function in psoriasis vulgaris.

Polymorphonuclear leukocyte (PMN) migration was assessed in vitro using the agarose plate method in patients with psoriasis vulgaris, and compared with an age- and sex-matched control group. No significant difference was found between the two groups in the PMN response to the chemotactic substances F-Met-Leu-Phe (FMLP) or zymosan activated serum (ZAS). Equally, the chemokinetic or chemotactic potential of psoriatic serum did not differ from control serum. Our results do not support a primary abnormality of PMN function in psoriasis.

Arthritis↗
PubMed1986

The effect of indomethacin on the renal response to arginine vasopressin in man.

The renal response to graded intravenous infusions of arginine vasopressin (AVP) was investigated in a two part study in six volunteers. First, under maximal water diuresis, seven control incremental infusions of AVP were given from zero to 12 fmol min-1 kg-1. Second, the AVP infusions were repeated after pretreatment with indomethacin, 150 mg daily for 36 h. After the AVP infusions, plasma AVP concentrations did not change significantly and remained within the physiological range; in contrast, urinary AVP excretion rate increased steadily. Indomethacin did not alter the plasma or urinary concentrations of AVP. AVP caused a fall in urine flow rate from a state of maximal diuresis to one of maximal antidiuresis. After indomethacin, fractional free water clearance was reduced by an average of 26% at the zero, 2 and 4 fmol min-1 kg-1 infusion rates of AVP. A significant increase in fractional sodium clearance of approximately 50% occurred during the AVP infusions, which was abolished after pretreatment with indomethacin. After indomethacin, urinary prostaglandin E2 (PGE2) excretion rate was reduced by an average of 40% at the zero and 2 fmol min-1 kg-1 infusion rates of AVP. At higher AVP infusion rates, no significant inhibition of PGE2 was observed. Urinary kallikrein excretion rate decreased steadily to one-third of its original value after AVP and this change remained unaltered by indomethacin. The findings show that infusions of AVP, resulting in plasma concentrations in the physiological range, evoke a maximal antidiuretic response, which is accompanied by natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗