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Biomedical subjects

R Grahame

Publications and source records attributed to R Grahame.

At least 19 recordsLinked to original sources

The Marfan syndrome: joint and skin manifestations are prevalent and correlated.

The objective of the study was to ascertain the occurrence and inter-relationships of locomotor symptoms, joint hypermobility and skin involvement in patients with the Marfan syndrome. A single clinical evaluation, using a standardized protocol, of randomly selected out-patients was made. Joint hypermobility was measured by two scales in wide clinical use (Beighton and Contompasis), skin hyperextensibility was assessed on the dorsum of the hand, and skin thickness and light transmissibility was measured at the same site with a modified Harpenden caliper. The setting was an out-patient medical genetics clinic at an urban teaching hospital in Baltimore, Maryland, USA. The subjects comprised 27 children and 48 adults who met strict diagnostic criteria for the Marfan syndrome. In patients less than 18 yr old, 70% had experienced at least one locomotor syndrome, and 40% had had multiple symptoms, of which arthralgia, myalgia and ligamentous injury were the most frequent. Symptoms were absent in children younger than 5 yr. Thereafter, the number of symptoms increased with age. Considerable joint hyperextensibility (> 3/9 of Beighton's criteria) was present in 85%. While one-third had received orthopaedic attention, there had been little if any rheumatological input. In adult patients, locomotor symptoms had occurred in 96%, with 88% having experienced more than one complaint. Spinal pain, arthralgia, ligament injury and fracture were the most common. Most (81%) of the adults had some (> 1/9), and 56% had considerable (> 2/9) evidence of joint hypermobility. Only 20% had received specialist attention for their locomotor symptoms. Skin changes are documented in the Marfan syndrome for the first time in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Symmetry of radiological features in the wrist and hands of patients with early to moderate rheumatoid arthritis: a quantitative microfocal radiographic study.

Quantitative microfocal radiography was used to assess the degree of symmetry in radiological features between the dominant and non-dominant wrist and hands of 51 patients with early to moderately advanced RA. With few exceptions, erosion size and joint space width were bilaterally symmetrical between the dominant and non-dominant side in: total erosion area and total joint space width; area at each of the separate sites of erosion formation, and width at each joint space; and the change in these X-ray features over an 18-month study period. Asymmetry in the number and size of erosions and joint space occurred in a small number of patients within either extremity; these differences were not sustained over the study period. In view of this degree of bilateral symmetry, the extent and progression of the radiographic features in RA can be assessed from a single macroradiograph of either the left or right wrist and hand.

Adult

The NSAID patch.

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Administration, Cutaneous

Local action transcutaneous flurbiprofen in the treatment of soft tissue rheumatism.

The objective of the present study was to establish the efficacy and tolerability of local action transcutaneous flurbiprofen (flurbiprofen LAT) in the treatment of soft tissue lesions. A randomized, double-blind, parallel-group placebo-controlled study was carried out in two hospital outpatient rheumatology clinics. One hundred and four patients aged 18-75 yr were randomized to receive a non-woven polyester-backed patch supporting a formulation containing 40 mg flurbiprofen 12-hourly over 14 days; or a non-medicated (but otherwise identical) control. Statistically significant differences in favour of the active preparation were seen at both days 7 (P = 0.02) and 14 (P = 0.009) for the investigator's overall opinion of severity of the condition, and at day 7 for the investigator's assessment of pain severity (P = 0.04 intention-to-treat; P = 0.052 N.S. eligible data). The need for further treatment in the form of steroid injections after the trial was greater in the controls (29/44, 66%) than in the flurbiprofen LAT group (17/46, 37%) (chi 2 = 7.54 on 1 d.o.f., P = 0.006). Plasma flurbiprofen levels in 11 patients ranged from 13.4 to 338.7 ng/ml (mean 116; median 57.9). Eight out of 53 (15%) patients receiving flurbiprofen LAT reported a total of 10 adverse events, compared with three out of 51 (6%) reporting seven events among controls. Patients found the patch convenient and soothing. We conclude that flurbiprofen LAT is an effective and acceptable treatment for soft tissue lesions, and should be considered as an alternative therapy to local steroid injection.

Administration, Cutaneous

Outcome assessment after epidural corticosteroid injection for low back pain and sciatica.

Epidural corticosteroid injection is a relatively effective treatment for low back pain and sciatica with a low incidence of side effects, although the patient's perspective in terms of outcome and satisfaction has not been studied well. The assessment of outcome in low back pain patients is complex. Three types of measure were compared: 1) a clinical score, 2) patient ratings of pain and disability, and 3) patient satisfaction ratings. There were significant discrepancies among the results. Consequently, clinical trials using different outcome measures may reach different conclusions. It therefore is vital to have planned the study carefully in advance, considering the questions to be asked, especially in this area, where patient-derived measures (e.g., "patient satisfaction") are so important. This study of 35 patients showed a fall in clinical signs/symptoms, disability, and pain 1 week after the injection, with maintenance of the reduction in disability at 3 months. Eighty-five percent reported at least some improvement at 1 week and 43% had improvement lasting 3 months. Patients with a more depressed mood had higher levels of disability both before and after the procedure. Anxiety before the procedure did not adversely affect outcome, and it was well tolerated by most patients. At 3 months 83% were satisfied with the treatment they had received and a patient satisfaction questionnaire gave similar results. We continue to recommend this treatment as a well-tolerated procedure, with which most patients are satisfied.

Adrenal Cortex Hormones

Pharmacokinetics of single oral doses of feprazone in patients with rheumatoid arthritis or with impaired renal clearance.

1. The pharmacokinetics of feprazone have been studied in 10 patients with rheumatoid arthritis (RA), and in a further six patients with renal impairment (RI) who were not suffering from rheumatoid disease. 2. For RA patients, the mean elimination half-life (t1/2) of feprazone after a single oral dose was 21 +/- 5 h (SD), the mean apparent clearance (Cl) was 0.012 +/- 0.009 l/h per kg, and the mean apparent volume of distribution (Vd) was 0.33 +/- 0.17 l/kg. Corresponding values for RI patients were 25 +/- 13 h, 0.016 +/- 0.011 l/h per kg, and 0.46 +/- 0.24 l/kg, respectively. 3. These results show no impairment of the elimination of feprazone in RA or RI patients; Vd and Cl are greater than in healthy young volunteers or elderly subjects, the AUC values are lower, but t1/2 values are similar in all groups. 4. It is suggested that the greater Cl and Vd, and lower AUC, in RA and RI patients may be due to renal insufficiency and decreased plasma protein binding of feprazone and its metabolite, or to induction of glucuronyl transferase activity by the prior medication, thus enhancing the formation of the major metabolite, the C(4)-glucuronide, and increasing drug elimination.

Administration, Oral

Ventricular septal aneurysm in a case of Ehlers-Danlos syndrome.

Cardiac abnormalities are a recognised feature of connective tissue disorders. We report a case of Ehlers-Danlos syndrome associated with an aneurysm of the membranous ventricular septum and mitral valve prolapse. To our knowledge this is the first reported association of Ehlers-Danlos syndrome and ventricular septal aneurysm.

Adolescent

Segregation analysis of collagen genes in two families with joint hypermobility syndrome.

We carried out a segregation analysis comparing the inheritance of collagen gene markers and joint hypermobility syndrome in two extended families. Our results exclude the genes encoding type III (COL3A1), type V alpha 2 chain (COL5A2) and type VI alpha 3 chain (COL6A3) unambiguously in both families. The simultaneous exclusion of both the type 1 alpha 1 and alpha 2 chain genes in the same family was not possible: COL1A1, but not COL1A2 was excluded in one and COL1A2, but not COL1A1 was excluded in the second. There was no suggestion of strong linkage to either of these loci. These data do not support the hypothesis that JHS in these families is caused by mutations in these collagen genes.

Adult

Monoclonal antibody treatment in rheumatoid arthritis: the clinical and immunological effects of a CD7 monoclonal antibody.

Six patients with rheumatoid arthritis were treated with a CD7 mouse monoclonal antibody, RFT2, daily for 15 days. Only two patients had a significant improvement in clinical disease activity which lasted 7-14 days. No serious adverse effects occurred although all patients developed antibodies against mouse immunoglobulin. During treatment T-lymphocyte numbers decreased and T-lymphocyte CD7 expression was absent in all but one patient.

Adult

Toward a rational therapeutic strategy for arachnoiditis. A possible role for d-penicillamine.

Twenty-six patients (13 men and 13 women), ranging in age from 38 to 75 years, with surgical and/or radiculographic evidence of chronic adhesive spinal arachnoiditis (CASA) were admitted to a randomly allocated, double-blind, 6-month crossover trial of d-penicillamine (500 mg/day) versus matching placebo. Assessments using subjective and objective criteria at 3-month intervals demonstrated no statistically significant effect with either d-penicillamine or placebo or between them. Thirteen of the 17 patients completing the trial expressed no clear preference. One patient preferred placebo. The remaining three patients who expressed strong preference for d-penicillamine (supported by objective data) subsequently maintained improvement on long-term therapy for up to 5 years. It is concluded that there may be a small subgroup of patients with CASA who might benefit from d-penicillamine therapy.

Adult

A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of rheumatoid arthritis.

A multi-centre, double-blind, crossover study was carried out in 80 patients with rheumatoid arthritis to compare the efficacy and side-effect profiles of two formulations of indomethacin. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times a day for a period of 4 weeks before being crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by both investigator and patient indicated that controlled-release indomethacin tablets, 75 mg given at night, was as efficacous as immediate-release indomethacin capsules given 3-times daily. However, the controlled-release formulation had a superior side-effect profile with a reduced incidence of abdominal/epigastric pain compared to the immediate-release preparation.

Administration, Oral

A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of osteoarthritis.

The efficacy and side-effect profiles of two formulations of indomethacin were compared in a multi-centre, double-blind, crossover study in 77 patients with osteoarthritis. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times daily for a period of 4 weeks, after which patients were crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by the investigator and patient indicate that controlled-release indomethacin tablets, 75 mg given at night, were as efficacious as immediate-release indomethacin capsules, 25 mg given 3-times daily, in the treatment of osteoarthritis. The side-effect profiles of the two formulations were similar.

Administration, Oral