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Biomedical subjects

M Doherty

Publications and source records attributed to M Doherty.

At least 217 records · Page 12Linked to original sources
PubMed1989

A new TATA box mutation detected at prenatal diagnosis for beta-thalassemia.

During the course of prenatal diagnosis for beta-thalassemia in Chinese patients, we encountered a mutation that was not detectable by oligonucleotides for the known Chinese mutations. Amplification of the beta-globin gene by the polymerase chain reaction and direct DNA sequencing revealed a previously undescribed -30 TATA box mutation which was carried by the father. Prenatal diagnosis was achieved, and the fetus did not inherit this beta-thalassemia allele.

Amniocentesis↗
PubMed1988

Synovial fluid collagenase in patients with destructive arthritis of the shoulder joint.

We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red-positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients.

Apatites↗
PubMed1988

Bilateral adhesive capsulitis, oligoarthritis and proximal myopathy as presentation of hypothyroidism.

A patient who presented with bilateral adhesive capsulitis of the shoulder, oligoarthropathy and rapidly progressive proximal myopathy is described. Although clinically euthyroid, autoimmune and biochemical hypothyroidism was the only predisposing factor found. Clinical deterioration after initiation of thyroxine replacement was followed by delayed improvement with reduction in initially elevated ESR and CRP.

Arthritis↗
PubMed1988

Increased concentrations of proteoglycan components in the synovial fluids of patients with acute but not chronic joint disease.

Synovial fluid samples (139) from 121 patients with rheumatoid arthritis, osteoarthritis, pseudogout, chronic pyrophosphate arthritis, gout, and reactive arthritis were analysed for cartilage proteoglycan components. Keratan sulphate (KS) epitope was determined by a competitive radioimmunoassay, and total sulphated glycosaminoglycans (S-GAG) were determined after papain digestion by a specific dye binding assay. Increased concentration of both KS epitope and S-GAG were found in synovial fluid from joints with acute inflammatory arthropathy (gout, pseudogout, and reactive arthritis). Analysis of consecutive samples from the same joint at different stages showed that the concentration of KS epitope or total S-GAG varied with acute inflammatory activity. In samples from patients with chronic conditions during active and inactive inflammatory phases concentrations were much lower and not distinguishable among these disease groups. The detection of raised concentration of proteoglycan components may reflect the rapid depletion or greatly increased turnover of proteoglycan in the articular cartilage during acute inflammation in the joint. This did not appear to be sustained in most patients with chronic joint diseases.

Acute Disease↗
PubMed1988

Relation between synovial fluid C3 degradation products and local joint inflammation in rheumatoid arthritis, osteoarthritis, and crystal associated arthropathy.

C3 degradation products (C3dg/d) were estimated in 288 synovial fluid (SF) samples (rheumatoid arthritis (RA) 93, osteoarthritis (OA) 68, chronic pyrophosphate arthropathy 80, acute pseudogout 20, others 27) from knees of 138 patients (bilateral 67, serial sampling on two to six occasions 40). At each aspiration knees were defined as 'active' or 'inactive' by single observer global assessment using six clinical parameters of inflammation. Lack of correlation between paired SF and plasma C3dg/d implied local C3 activation within joints. Raised SF C3d levels were found in active compared with inactive RA joints (mean (range) 51 (15-105) and 6 (0-15) units/ml respectively). Low SF C3dg/d levels were found in OA (mean (range) 0.8 (0-7) units/ml) and chronic pyrophosphate arthropathy (mean (range) 4 (0-16) units/ml), irrespective of clinical activity. In contrast, very high levels (mean (range) 61 (16-126) units/ml) were present in all cases of pseudogout. These differences remained after correction for SF C3 or albumin. This study is the first to show a positive correlation between SF C3dg/d and local inflammation in RA joints. It further suggests that C3 activation is a constant feature of pseudogout but not an accompaniment of inflammation associated with chronic crystal associated synovitis or OA.

Adult↗
PubMed1988

Clinical aspects of calcium pyrophosphate dihydrate crystal deposition.

CPPD deposition occurs in a wide variety of clinical settings, most commonly as an age-related phenomenon in the absence of other joint abnormality. Although our knowledge of CPPD and other intra-articular particles has increased in the last decade, the role of CPPD remains unclear. The paradox of asymptomatic deposition of phlogistic crystals, the wide spectrum of clinical presentation, and the lack of disease specificity, however, have challenged recognition of pyrophosphate arthropathy (PA) as a separate, distinct disease entity and led to reappraisal of earlier concepts of crystal deposition disease. In this article, clinical aspects of PA will first be presented; the validity of PA as a discrete arthropathy will then be discussed.

Arthritis↗
PubMed1988

Peripheral nerve entrapment at the wrist in pyrophosphate arthropathy.

Of 200 consecutive patients with confirmed pyrophosphate arthropathy, clinically significant median nerve entrapment was found in 14 (14%) of those with wrist involvement. Three of these had electromyographically confirmed combined median and ulnar nerve entrapment at the wrist (bilateral in 2). Chondrocalcinosis, but not changes of arthropathy, was closely associated with the presence of entrapment (p less than 0.001), implying that soft tissue factors are important in causation. Treated hypothyroidism was more common in those with nerve entrapment (p less than 0.01), suggesting a possible interaction of multiple factors in the pathogenesis of nerve entrapment.

Adult↗
PubMed1988

Mixed crystal deposition.

Mixtures of crystals are found in joint tissues more commonly than would be expected by chance. In osteoarthritic joints, for example, mixtures of different calcium salts are more common than any one type of crystal alone. This is partly explained by the predisposing factors and mechanisms of crystal formation, many of which are not salt specific. It is suggested that rheumatic disorders should not be diagnosed or classified by crystal type.

Calcinosis↗
PubMed1987

An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to hemophilia A.

We report the development of a rapid nonradioactive technique for the genetic prediction of human disease and its diagnostic application to hemophilia A. This method is based on enzymatic amplification of short segments of human genes associated with inherited disorders. A novel feature of the procedure is the use of a heat-stable DNA polymerase, which allows the repeated rounds of DNA synthesis to proceed at 63 degrees C. The high sequence specificity of the amplification reaction at this elevated temperature permits restriction-site polymorphisms, contained in the amplified samples, to be analyzed by visual inspection of their digestion products on polyacrylamide gels. By means of this method, we have performed carrier detection and prenatal diagnosis of hemophilia in two families with use of the factor VIII intragenic polymorphisms identified by the restriction enzymes BclI and XbaI. Predictions can be made directly from chorionic villi, without previous DNA extraction, and fetal sex can be determined by amplification of sequences specific for the Y chromosome. Specific amplification of genomic sequences with heat-stable DNA polymerase is applicable to the diagnosis of a wide variety of inherited disorders. These include diseases diagnosed by restriction-site variation, such as Duchenne's muscular dystrophy and sickle cell anemia, those due to a collection of known mutations, such as beta-thalassemia, and those due to gene deletion, such as alpha-thalassemia.

Base Sequence↗
PubMed1987

Audit of work at a medical centre for the homeless over one year.

An audit of one years' work at a voluntary health care service for the homeless involving doctors, a chiropodist, nurses and social workers was carried out. It was found that although certain health problems are more common among the homeless than in the general population, the range resembles that in any general practice. However, registration with general practitioners was much less common among the homeless than in the general population, and a high proportion of referrals to hospital did not lead to appropriate treatment. The value of a special primary health care service for the homeless is discussed.

Adult↗