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Biomedical subjects

M Doherty

Publications and source records attributed to M Doherty.

At least 109 records · Page 6Linked to original sources
PubMed1992

Tophaceous pyrophosphate deposition with extensor tendon rupture.

Tophaceous deposition of calcium pyrophosphate dihydrate (CPPD) crystals is considered unusual as is deposition within tendon sheaths. Associated tendon rupture is described but is rare. We report a lady with tophaceous CPPD deposition at the wrist, a previously unreported site. Contrary to previous cases, this occurred in the setting of symptomatic, polyarticular, pyrophosphate arthropathy. An additional point of interest was development of associated extensor tendon rupture with features favouring a non-inflammatory mechanism of tendon damage.

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PubMed1992

Autoantibodies, immunoglobulins and Gm allotypes in nodal generalized osteoarthritis.

The frequencies of autoantibodies, including class specific rheumatoid factors, Gm allotypes, and levels of immunoglobulins were determined in 86 patients with nodal generalized osteoarthritis (NGOA), 79 patients with non-nodal large joint osteoarthritis (LJOA), and 90 non-osteoarthritic controls. NGOA patients had a higher frequency of IgG rheumatoid factor (P less than 0.0001) compared to LJOA and normal subjects. Both osteoarthritic groups had lower mean levels of IgA than normals (P less than 0.05), and NGOA patients had a higher frequency of subnormal IgA levels than normals. No differences in other rheumatoid factors nor in frequencies of Gm allotypes were seen. These data support characterization of NGOA as a distinct subset of osteoarthritis, and suggest involvement of immune processes in its pathogenesis.

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PubMed1992

The treatment of osteoarthritis.

1. The treatment of osteoarthritis is currently purely symptomatic. To enable rational therapy, careful clinical assessment is necessary to identify the origin of symptoms. Often, effective therapy can result from a biomechanical approach such as surgery, orthotics, physiotherapy and dieting. If drugs are required, there is little evidence that the current over-reliance on non-steroidal anti-inflammatory drugs (NSAIDs) is justified. Full dose regular paracetamol should be the first line of analgesic therapy. In the majority of patients, simple analgesics are probably as effective as NSAIDs. If NSAIDs are used it is necessary to review regularly their use and to be aware of potential toxicity. 2. Many alternative strategies of pain management such as topical preparations, intra-articular steroid injections, acupuncture, radiosynovectomy, transcutaneous nerve stimulation and anti-depressants, may be effective but their precise place in the armamentarium is not yet fully established. 3. The realisation that osteoarthritis is not a passive 'wear and tear' phenomenon but an active process that may be potentially modified, has led to interest in 'chondroprotective' agents, which may beneficially affect the osteoarthritic process. To date there are no convincing data available that such agents are, in fact, chondroprotective in humans.

Analgesia↗
PubMed1992

Radiographic patterns and associations of osteoarthritis of the hip.

A number of patterns of osteoarthritis of the hip are described, though studies are conflicting with respect to the frequency of such patterns and their associations. Two hundred and eleven patients (133 women, 78 men; mean age 66 years, range 29-86) referred to hospital with osteoarthritis of the hip were studied. Involvement was unilateral in 108 (51%) and bilateral in 89 (42%); 14 (7%) had undergone arthroplasty and were presenting with osteoarthritis hips). Sixty one per cent of hips had severe, 28% moderate, and 11% mild changes (Kellgren grade). Superior pole migration occurred in 82% (46% superolateral, 25% intermediate, 11% superomedial), medial/axial migration occurred in only 8%, and in 10% the pattern was indeterminate. In bilateral osteoarthritis of the hip the pattern was generally symmetrical. Superomedial and medial/axial patterns were proportionately more common in women, whereas superlateral osteoarthritis predominated in men. No association was found between multiple clinical nodes, radiographic polyarticular interphalangeal or first carpometacarpal osteoarthritis and any migration pattern. Any interphalangeal osteoarthritis was negatively associated with medial migration. Only 40% of hips could be categorised as hypertrophic or atrophic; chondrocalcinosis at any site was associated with atrophic osteoarthritis; no associations were seen with Forestier's disease. This large survey confirms the association between chondrocalcinosis and atrophic osteoarthritis of the hip. Importantly it suggests that gender, rather than associated osteoarthritis at other sites, is a major determinant of the pattern of osteoarthritis of the hip.

Adult↗
PubMed1992

The 'GALS' locomotor screen.

The locomotor system is complex and difficult to examine. A selective clinical process to detect important locomotor abnormalities and functional disability could prove valuable. A screen based on a tested 'minimal' history and examination system is described, together with a simple method of recording. The screen is fast and easy to perform. As well as providing a useful introduction to examination of the locomotor system, the screen includes objective observation of functional movements relevant to activities of daily living. Its inclusion in the undergraduate clerking repertoire could improve junior doctors' awareness and recognition of rheumatic disease and general disability. It could also provide a valuable screening test for use in general practice.

Humans↗
PubMed1992

Evaluation of a method for clinically assessing osteoarthritis of the knee.

A system for assessing symptoms (pain, stiffness, gelling) and signs (local temperature, effusion, tenderness, synovial swelling, popliteal cyst, crepitus) of osteoarthritis of the knee has been developed. The system has been assessed for intra- and interobserver variation using normal and osteoarthritic knees. Intraobserver variability is low for all indices but interobserver variability is high for physical signs. It is suggested that the components within this system, when applied by a single observer, may provide a reasonable framework for clinical assessment of osteoarthritis of the knee.

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PubMed1992

The efficacy of Arthrotec in the treatment of osteoarthritis.

In a double-blind study, 455 patients with osteoarthritis were randomly assigned to receive a combination of Arthrotec, 50 mg of diclofenac and 200 micrograms of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 4 weeks. At weeks 2 and 4 of treatment, no significant differences between the treatment groups were noted in changes from baseline on the physicians' and patients' global assessment of osteoarthritis. On a measure of arthritis severity, patients with both arthritis of the hip and knee showed improvement from week 2 to week 4, with no significant differences between treatment groups.

Administration, Oral↗
PubMed1992

Autologous bone marrow transplantation for acute myelogenous leukemia using 4-hydroperoxycyclophosphamide and VP-16 purged bone marrow.

Thirty adult patients with acute myelogenous leukemia (AML) in remission were treated with hyperfractionated total body irradiation, VP-16, and cyclophosphamide followed by infusion of autologous bone marrow purged with 4-hydroperoxycyclophosphamide and VP-16. Fifteen patients were transplanted in first remission (R1), 13 in second remission (R2), and two in third remission (R3). All patients had hematopoietic engraftment. The median time to achieve a white blood cell count of 1.0 x 10(9)/l and a neutrophil count of 500 x 10(6)/l was 32 days. The median time to achieve an unsupported platelet count of 50 x 10(9)/l was 70 days. There were four transplant-related deaths, all in patients in R2. Ten patients have relapsed, including both patients transplanted in R3. The disease-free survival (DFS) of all patients is 52%, median follow-up not yet reached. Although the number of patients in each group is small and follow-up is limited, there is a trend toward improved actuarial DFS in patients transplanted in R1 compared with patients transplanted in R2 (72 vs 39%; p = 0.081). Use of VP-16 in the conditioning regimen as well as in the purging procedure is feasible in the treatment of patients with AML.

Adult↗
PubMed1992

Teaching rheumatology to medical students: current practice and future aims.

Rheumatological disease is common but is often overlooked or inadequately assessed by doctors. This may reflect training in the discipline. The results of a survey of all British medical schools by the Arthritis and Rheumatism Council and the British Society for Rheumatology show that clinical rheumatology teaching forms a small part of most courses (median 4, range 0-8 weeks), usually as a second-year specialty attachment, and that specific assessment of basic clinical skills in rheumatology is often not undertaken. The results of the survey support the idea that the current teaching of rheumatology might help to marginalise the subject rather than to promote it.

Curriculum↗
PubMed1991

Inorganic pyrophosphate in metabolic diseases predisposing to calcium pyrophosphate dihydrate crystal deposition.

Inorganic pyrophosphate (PPi) levels were estimated by radiometric assay in urine and in synovial fluid (SF) from asymptomatic, nonarthritic knees of patients with untreated metabolic disease and normal controls. SF PPi was significantly elevated in patients with hyperparathyroidism (mean +/- SEM 19 +/- 3 microM; n = 9), hemochromatosis (23 +/- 5 microM; n = 6), and hypomagnesemia (27 +/- 0.1 microM; n = 2) compared with normal subjects (10 +/- 0.5 microM, n = 50), and was low in patients with hypothyroidism (4.2 +/- 2.3 microM; n = 11) (P less than 0.05 all comparisons). Urinary PPi was elevated only in those with hypophosphatasia. Local elevation of ionic PPi may be relevant to the mechanism of crystal formation in metabolic diseases predisposing to calcium pyrophosphate dihydrate (CPPD) crystal deposition. The finding of low SF PPi levels in patients with hypothyroidism further questions the association between this condition and CPPD.

Adult↗
PubMed1991

Behavioral evidence of depolarization block of mesencephalic dopamine neurons by acute haloperidol in partially 6-hydroxydopamine-lesioned rats.

The effects of acute haloperidol (HAL) and apomorphine (APO) administration were tested on the responsiveness of rats to medial forebrain bundle (MFB) brain stimulation reward (BSR) before and 28 days after partial dopamine (DA) depletion. Before 6-hydroxydopamine (6-OHDA) lesioning, HAL (50-100 micrograms/kg) and APO (25 micrograms/kg) both caused moderate decreases in the animals' responsiveness to BSR. In contrast, the same moderate doses of HAL completely abolished BSR after lesioning. However, postlesion responding for BSR after HAL could be reinstated by APO. The results of this study provide behavioral evidence that is consistent with recent electrophysiological data showing that acute HAL causes DA cells that survive 6-OHDA lesions to be driven into a state of depolarization block.

Animals↗
PubMed1991

Familial chondrocalcinosis due to calcium pyrophosphate dihydrate crystal deposition in English families.

Familial predisposition to chondrocalcinosis (CC) due to calcium pyrophosphate dihydrate (CPPD) crystal deposition is described in five English kindreds. Two families were characterized by premature-onset polyarticular CC with little associated structural arthropathy. In one of these families, recurrent childhood fits were strongly associated with subsequent development of CC. Affected members of the other three families resembled sporadic disease in showing predominantly late-onset, oligoarticular CC with mild arthritis and destructive change in only one case. Knee synovial fluid levels of inorganic pyrophosphate (PPi) and nucleoside triphosphate pyrophosphate (NTPP) did not differ from those of 59 sporadic cases of CC due to CPPD, although PPi and NTPP levels in both groups were higher than in normal knee synovial fluid (P less than 0.0001). Urinary PPi levels were not different from normal controls. Screening for other metabolic abnormality was negative in all cases. This is the first report of familial CC in the UK, and the first to associate this condition with childhood fits. Absence of overt primary abnormality of PPi metabolism suggests that other factors relating to crystal nucleation/growth may be more relevant to predisposition in these cases.

Calcium Pyrophosphate↗
PubMed1991

Inorganic pyrophosphate, nucleoside triphosphate pyrophosphatase, and cartilage fragments in normal human synovial fluid.

The association between calcium pyrophosphate dihydrate (CPPD) crystal deposition and ageing is unexplained. Levels of inorganic pyrophosphate (PPi) and activity of nucleoside triphosphate pyrophosphatase (NTPP) were estimated in synovial fluid from 91 asymptomatic normal knees, including five with isolated CPPD crystal deposition (70 subjects; median age 47, range 22-83 years). In non-crystal fluids, PPi levels and NTPP activities were low (median, interquartile range: 9.5, 7.6-12.3 microM, and 1, 0.4-2 microM/30 min/mg protein, respectively: n = 50) and a generalized increase with age was not demonstrated. Higher values for PPi and NTPP in all five subjects with isolated CPPD deposition supports involvement of altered PPi metabolism, unrelated to ageing per se, in crystal formation. Presumed cartilage fragments were identified by morphological characteristics in 70% of normal fluids: metachromatic staining and electron microscopy, undertaken in a limited number, supported identification of such particles as cartilage. This finding supports dynamic turnover of healthy matrix, and questions the usefulness of identification, without quantification, cartilage fragments as a measure of cartilage damage.

Adult↗
PubMed1991

A limited association of generalized osteoarthritis with alleles at the type II collagen locus: COL2A1.

A significant genetic influence in osteoarthritis has been observed in the combination of Heberden's nodes and generalized osteoarthritis. We examined whether mutation in the gene encoding the major cartilage matrix protein type II collagen was responsible by comparing allele frequencies at the locus (COL2A1) in a group of 61 patients with nodal GOA with a control population and by analysing the COL2A1 genotypes of 21 affected sibling pairs. There were no significant allele differences but a slightly increased tendency over chance alone for affected siblings to have inherited the same COL2A1 alleles from their parents.

Alleles↗
PubMed1991

Absence of autoimmunity to type II collagen in generalised nodal osteoarthritis.

A cardinal feature of generalised nodal osteoarthritis is the loss of articular cartilage. To determine if autoimmunity to these cartilage collagens occurred, serum antibodies to native and denatured type II collagen were measured by enzyme linked immunosorbent assay (ELISA) in 96 patients (90 women, six men, aged 47-91 years) with generalised nodal osteoarthritis. Generalised nodal osteoarthritis was diagnosed by typical clinical and radiological features. Serum samples from 42 blood donors were assayed as controls. No significant difference was found between the patients with generalised nodal osteoarthritis and the controls. Furthermore, the 20 patients who were HLA-A1, B8 positive had similar antibody levels to the group as a whole. One woman patient with generalised nodal osteoarthritis (HLA-A1, B8 negative) had markedly increased antibody levels to native and denatured type II collagen in a pattern similar to that seen in patients with rheumatoid arthritis. This patient did not develop super added rheumatoid arthritis during a three year follow up period. Autoimmunity to type II collagen is therefore rare in generalised nodal osteoarthritis. A lack of collagen antibodies in a condition characterised by hyaline cartilage loss suggests that the presence of such antibodies in rheumatoid arthritis is more than a secondary event to joint damage.

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