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Biomedical subjects

M Doherty

Publications and source records attributed to M Doherty.

At least 55 records · Page 3Linked to original sources
PubMed1993

Is osteoarthritis in women affected by hormonal changes or smoking?

The influence of sex hormone related events and smoking on the development of OA in women was investigated in a case-controlled postal survey. One hundred and twenty-nine patients with nodal generalized osteoarthritis (NGOA) and 145 with non-nodal pauciarticular large joint osteoarthritis (LJOA) were identified from the database of a Nottingham OA clinic. For each patient, three age-matched controls were randomly selected from the same general practice. Sixty-three per cent of questionnaires (690/1096) were returned: NGOA, 95; NGOA controls, 226; LJOA, 113; LJOA controls, 256. There were no differences in age at menarche or menopause, rates of hysterectomy, oral contraceptive use, or hormone replacement use between cases and controls. Fewer OA patients had ever smoked [(Odds Ratio (OR) 0.65, 95% Confidence Interval (CI) 0.45-0.95)] and subset analysis demonstrated that this negative association occurred only in the LJOA group (OR 0.43, CI 0.25-0.72), particularly in those with knee OA (OR 0.29, CI 0.14-0.62). A previous successful pregnancy was negatively associated with NGOA (OR 0.47, CI 0.24-0.95). This study demonstrates no association between oestrogen-related hormonal events and OA, but a negative association between smoking and LJOA. Such data supports the concept that OA is a heterogeneous disease and underlines the need to differentiate OA subsets.

Age Factors↗
PubMed1993

Plasma concentration of fentanyl, with 70% nitrous oxide, to prevent movement at skin incision.

BACKGROUND: The Cp50 (minimal steady state plasma concentration of an intravenous analgesic/anesthetic required to prevent a somatic response in 50% of patients following skin incision) and the Cp50-BAR (minimal plasma concentration of an analgesic/anesthetic required to prevent either a somatic, hemodynamic, or autonomic response in 50% of patients following skin incision) have been recently proposed as a measure, like minimum alveolar concentration (MAC; and MAC-BAR), to establish the relative potency of intravenous analgesics. This study was conducted to establish the Cp50 for fentanyl. METHODS: Unpremedicated patients were administered fentanyl (in the presence of 70% N2O) via computer-assisted continuous infusion, a pharmacokinetic model-driven infusion device. After induction of anesthesia with fentanyl, the randomized target fentanyl concentration was entered into computer-assisted continuous infusion. This target fentanyl concentration was maintained until skin incision. Before induction, prior to skin incision, and immediately after skin incision, arterial blood samples were obtained for measurement of fentanyl and norepinephrine concentrations. At skin incision, patients were observed for a somatic, hemodynamic, or autonomic response. Only patients in whom the pre- and postincision fentanyl concentrations were within +/- 30% were included in the calculation of the Cp50. The Cp50 was calculated using logistic regression. RESULTS: The Cp50 for fentanyl was 3.26 ng/ml, and the Cp50-BAR was 4.17 ng/ml. CONCLUSIONS: Comparing these results with the previously published Cp50 of alfentanil, the potency of fentanyl relative to alfentanil is 1:58. Establishing the Cp50, once effect site equilibration has occurred, will allow pharmacodynamic comparisons between the opioids at equipotent concentrations.

Adult↗
PubMed1993

Association of radiographic changes of osteoarthritis, symptoms, and synovial fluid particles in 300 knees.

Associations between compartmental distribution of radiographic changes of osteoarthritis (OA), individual features of OA (joint space loss, sclerosis, cyst, osteophyte; each scored 0-3), and presence of synovial fluid calcium particles (calcium pyrophosphate dihydrate (CPPD) crystals identified by polarised light microscopy and other calcium particles by alizarin red positivity (ARP) were sought in 300 osteoarthritic knees (178 patients; mean age 72, range 33-96 years). Patients whose knees were symptom free as well as those with symptoms were included. Osteoarthritis of two or three compartments but not unicompartmental OA was associated with the presence of CPPD or ARP. Involvement of any compartment (not just patellofemoral), and higher mean scores for both total and individual osteoarthritis changes (except cysts) was associated with CPPD and ARP; CPPD, but not ARP, was associated with symptoms: knees reported as having symptoms had higher mean total OA scores. Femoral cortical erosion, found more often in women, was associated with higher mean total OA score at the patellofemoral compartment but not with the presence of particles. Attrition, remodelling, and chondrocalcinosis (each scored as present or absent) occurred more often in knees with CPPD. Age did not correlate with any aspect of the OA score. This study confirms the association of calcium particles with the process of OA. Unlike previous studies confined to symptomatic knees, a radiographic pattern specific to CPPD ('pyrophosphate arthropathy') did not emerge.

Adult↗
PubMed1993

Radiographic progression of hospital referred osteoarthritis of the hip.

Various factors have been considered important in the rate of progression of osteoarthritis of the hip, though few data are available from large longitudinal studies. One hundred and thirty six patients referred to hospital (85 women, 51 men; mean age 65 years, range 29-86 years) with osteoarthritis of the hip (192 affected hips) were followed up for a median of 27 (range 3-72) months. One hundred and six patients (144 affected hips) were reviewed for a minimum of one year (median 28, range 12-72 months). Fifty three per cent of all osteoarthritic hips required an operation at a median of 14 (range 3-48) months from entry. All radiographs before and after entry were examined (median four films for each patient over a median of three years, range 0.5-19 years). Hips showing rapid radiographic progression on prospective films more often had superior migration, or an atrophic bone response; those with no progression more often had an indeterminate, medial, or axial migration pattern, protrusio or mild osteoarthritis at presentation. A higher occurrence of rapid progression was seen in women, in those of older age at symptom onset, and in hips with a higher Kellgren grade at entry; men more often showed no progression. Age at presentation, body mass index, symptom duration, or presence of chondrocalcinosis, hand osteoarthritis/nodes, or Forestier's disease did not influence progression. This study supports the contention that, at the time of hospital referral, certain patient characteristics and radiographic features at the hip may help to identify those at high risk of rapidly progressive hip osteoarthritis.

Adult↗
PubMed1993

Rapid development of a tophus following ipsilateral hemiparesis.

An 85 year old man with a longstanding history of non-tophaceous gout developed a single large tophus, unassociated with inflammation, on his paretic leg over a six week period following an acute hemiplegia. The rapidity of tophus formation, its localisation to the paretic limb, and the apparent blunting of the acute inflammatory response represent a previously unreported interaction between gout and neurological deficit.

Acute Disease↗
PubMed1993

Radiographic patterns and associations of osteoarthritis of the knee in patients referred to hospital.

OBJECTIVES: To investigate differing patterns and associations of osteoarthritis of the knee in patients referred to hospital. METHODS: Two hundred and fifty two consecutive patients (161 women, 91 men; mean age 70 years, range 34-91 years) referred to hospital with osteoarthritis of the knee underwent clinical, radiographic, and synovial fluid screening. RESULTS: Radiographic changes of osteoarthritis of the knee (definite narrowing with or without osteoarthritic features) were bilateral in 85% of patients. Of 470 knees affected, 277 (59%) were affected in two compartments and 28 (6%) in three compartments. Unilateral and isolated medial tibiofemoral osteoarthritis were more common in men. Calcium pyrophosphate crystal deposition was common (synovial fluid identification in 132 (28%) knees; knee chondrocalcinosis in 76 (30%) patients) and associated with disability, bilateral, multicompartmental and severe radiographic osteoarthritis, marked osteophytosis, attrition, and cysts. Multiple clinical nodes (58 (23%) patients) and radiographic polyarticular interphalangeal osteoarthritis (66 (26%) patients) were associated with a higher frequency of inactivity pain, disability, multicompartmental and severe radiographic change. Forestier's disease predominated in men but showed no other associations. CONCLUSIONS: In a group of patients referred to hospital osteoarthritis of the knee is usually bilateral and affects more than one compartment. Severe and multicompartmental radiographic changes are associated with calcium pyrophosphate crystal deposition, nodal change, and polyarticular interphalangeal osteoarthritis.

Adult↗
PubMed1993

Radiographic assessment of patellofemoral osteoarthritis.

OBJECTIVES: To determine the feasibility of assessing patellofemoral osteoarthritis using the 'skyline' view and to compare its reproducibility with the standard lateral view. METHODS: Fifty patients attending a rheumatology outpatient department with osteoarthritis of the knee had standard radiographs taken of both knees: standing weightbearing anteroposterior; lateral supine radiograph in 30 degrees of flexion; and a skyline view of the patellofemoral joint. After an initial training period using 20 sets of films the remaining 30 sets were read blind by five observers. Intraobserver and interobserver variability was assessed using the kappa statistic. The minimum joint space in each compartment was measured using a ruler. Two views of a single normal subject were measured to determine the effect of knee flexion. RESULTS: The final 30 study films were from 20 women and 10 men, median age 72.5, range 18-91 years. A grading system comprising assessment of osteophytosis, joint space narrowing, sclerosis, cysts, and attrition could easily be applied to the skyline patellofemoral view. Intraobserver reproducibility was better than the interobserver reproducibility for all features. The skyline view performed more reproducibly and over a wider range of categorisation for joint space narrowing than the lateral radiograph. Measurement using a ruler was easy to perform and precise to within 1 mm for the medial tibiofemoral and lateral facet of the patellofemoral joint. In normal knees the degree of flexion significantly affected the measurement. CONCLUSIONS: Radiographic grading of the skyline patellofemoral view is readily achieved, is more reproducible than assessment of the lateral view, and allows more precise localisation of change. Such views should be considered in radiological surveys of osteoarthritis of the knee.

Adolescent↗
PubMed1993

Cystic change in the head of the fibula in osteoarthritis.

We report eight patients with prominent cystic changes in the head of the fibula. Seven of these had osteoarthritis of the adjacent knee, and five had evidence of local deposition of calcium pyrophosphate dihydrate crystals. A radiographic survey of 470 knees in 254 patients with osteoarthritis suggested that such cysts are rare, but should be considered in the differential diagnosis of such changes before expensive or invasive investigations are performed.

Aged↗
PubMed1993

Eosinophilic fasciitis with late onset arthritis responsive to sulfasalazine.

We describe a patient with eosinophilic fasciitis in whom there was a late onset of inflammatory polyarthritis. Response of the arthritis to sulfasalazine was demonstrated, both initially and after a flare of synovitis which followed dose reduction. Sulfasalazine may be of benefit in this rare condition.

Adult↗
PubMed1993

Reflecting on scientific thinking: children's understanding of the hypothesis-evidence relation.

3 experiments were carried out to examine children's understanding of the role of covariation evidence in hypothesis formation. Previous research suggested that it is not until 8 to 11 years of age that children begin to understand how a given pattern of covariation supports a particular hypothesis about which factor is causally responsible for an observed effect. Experiments 1 to 3 employed a different (fake evidence) technique than previous research and showed that by 6 years of age most children understand how evidence would lead a story character to form a different hypothesis than the subject's own. Experiment 3 showed that most 6- and young 7-year-olds understand how a character's future actions (e.g., choice of an object) and predictions of future outcomes depend on the hypothesis he or she holds.

Child↗
PubMed1992

High-performance liquid chromatographic determination of naproxen, ibuprofen and diclofenac in plasma and synovial fluid in man.

High-performance liquid chromatographic assay procedures have been developed for naproxen, ibuprofen and diclofenac in human plasma and synovial fluid samples. A single liquid-liquid extraction procedure was used to isolate each compound from acidified biological matrix prior to the quantitative analysis. A Spherisorb ODS column (12.5 cm x 4.6 mm I.D.) was used for all the chromatography. Naproxen was eluted with a mobile phase of methanol-Sörensen's buffer at pH 7 (37:63, v/v). Ibuprofen and diclofenac were eluted using mobile phases of methanol-water at pH 3.3 (65:35, v/v and 63:37, v/v, respectively). Diphenylacetic acid was used as the internal standard for the assay of naproxen and flurbiprofen was used in the analysis of ibuprofen and diclofenac. Inter- and intra-day coefficients of variation were less than 7%. The assays were used in clinical studies of the three drugs in osteo- and rheumatoid arthritis patients.

Chromatography, High Pressure Liquid↗
PubMed1992

High-dose chemotherapy and autologous bone marrow rescue for patients with refractory germ cell tumors. Early intervention is better tolerated.

Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus autologous bone marrow rescue (AUBMR) was administered to 29 patients with advanced germ cell tumors (GCT) refractory to cisplatin-based chemotherapy. Two groups of patients with refractory disease were treated. Sixteen patients had been identified as "poor risk" at diagnosis and had an inappropriately slow decline of serum tumor markers after two cycles of induction cisplatin-based therapy (Group A). In addition, 13 patients were treated who had never had a complete response (CR) or had relapses after ifosfamide-based salvage chemotherapy (Group B). Patients in Group A were treated with high-dose carboplatin etoposide, and patients in Group B received high-dose carboplatin, etoposide, and cyclophosphamide. Fifteen of 29 (52%) patients had a CR (9, Group A; 6, Group B). The patients in Group A had fewer hematologic toxic effects, and the median number of days from day 0 to a granulocyte count greater than 0.5/microliters was 16 and to a platelet count of more than 50/microliters was 15, compared with 22 days and 23 days in Group B, respectively. There were fewer episodes of culture-positive sepsis in Group A (12%) compared with Group B (26%), and the only treatment-related death occurred in Group B. Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus AUBMR is effective for patients with GCT refractory to regimens of cisplatin with or without ifosfamide. Early use of high-dose chemotherapy reduces hematologic toxic effects and allows patients to start treatment in a more predictable fashion after cytoreduction, rather than when the disease is progressing rapidly.

Adult↗
PubMed1992

Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases.

OBJECTIVE: Recently, 2 classes of cytokine inhibitors have been defined at the molecular level. The largest group comprises the extracellular domains of cell surface cytokine receptors, and includes both tumor necrosis factor receptors (TNF-R). The present study was conducted to investigate the role of TNF inhibitors in arthritis. METHODS: We measured p55 and p75 soluble TNF-R (sTNF-R) in serum and synovial fluid (SF) samples from patients with rheumatic diseases and compared their levels with levels of soluble interleukin-2 receptors (sIL-2R). Sensitive enzyme-linked immunosorbent assays (ELISA), specific for p55 and p75 sTNF-R and for sIL-2R, were used. RESULTS: Serum levels of p75 sTNF-R were 3-4-fold higher than levels of p55 sTNF-R, and both were significantly elevated in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) compared with healthy controls. RA SF levels of sTNF-R were 4-5-fold higher than levels in serum, suggesting local production in the joint, and were significantly higher than levels in the SF of patients with seronegative arthropathy or OA. Furthermore, levels of p55 and p75 sTNF-R, but not sIL-2R or TNF alpha measured by ELISA, were increased in the SF of patients with clinically active RA. The soluble TNF-R in RA and OA SF were functional since they inhibited TNF activity in a cytotoxicity assay in proportion to the levels of inhibitor present. Evaluation of serially obtained serum samples suggested that sTNF-R may be a useful parameter for monitoring RA disease activity. CONCLUSION: Biologically active soluble TNF-R are up-regulated in patients with rheumatic disease and are produced locally in the joints. Measurement of serum levels of TNF-R may be useful for monitoring of disease, and determination of SF levels could be of diagnostic value.

Adult↗
PubMed1992

Diseases associated with calcium pyrophosphate deposition disease.

Although many metabolic and endocrine diseases have been reported to predispose to calcium pyrophosphate dihydrate crystal deposition, the validity of many of these associations remains unclear. A critical review of the literature relating to these associations, with illustrative cases and data derived from the authors' own experience, is presented. It is concluded that there is good evidence to associate hypophosphatasia, hypomagnesemia, and hyperparathyroidism with chondrocalcinosis and acute attacks of "pseudogout." Meta-analysis also suggests a small but significant association between hypothyroidism and chondrocalcinosis. Hemochromatosis stands alone in clearly associating not only with chondrocalcinosis but also with structural change and chronic arthropathy. The biochemical mechanisms that may produce these various associations are discussed. Recommendations are made concerning appropriate screening for metabolic and endocrine disease in patients with chondrocalcinosis.

Acromegaly↗
PubMed1992

Non-steroidal anti-inflammatory drug usage and requirement in elderly acute hospital admissions.

There is a strong feeling that despite the increasing awareness of their adverse effects, non-steroidal anti-inflammatory drugs (NSAIDs) are not always used appropriately. To examine this problem amongst elderly patients who may be at particular risk, 500 acute admissions to Health Care of the Elderly wards were studied prospectively. Sixty-five patients were currently receiving NSAIDs; 56 had medical conditions possibly caused by, or aggravated by NSAIDs. Indications for NSAIDs were often no longer apparent, and these drugs were successfully discontinued in 56; in 22 no alternative therapy was required. Importantly, following discharge the majority of patients remained off NSAIDs. These data support the need for continual review of NSAID requirements and regular monitoring for adverse effects, particularly in this high risk group.

Aged↗