Hazards of using a syringe to administer medications.
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Biomedical subjects
Publications and source records attributed to H Berry.
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OBJECTIVE: To compare the rate of radiographic progression in knee osteoarthritis (OA) comparing indomethacin with placebo and tiaprofenic acid with placebo. METHODS: Rate of radiographic progression of OA of the knees was studied in 812 patients randomized double blind parallel group study at 20 rheumatology clinics in the United Kingdom and analyzed sequentially. Patients received either indomethacin 25 mg three times daily, tiaprofenic acid 300 mg twice daily, or matched placebo. All had access to paracetamol as a rescue analgesic. Joint space narrowing was measured by a 6 point grading scale, using radiographs taken with a standardized technique at recruitment and annually thereafter. RESULTS: Three hundred and seventy six patients completed at least one year of study medication and therefore contributed evaluable results. More than twice as many patients showed deterioration in the indomethacin group as in the placebo group; of 170 available patients at the 3rd interim analysis, 40 of 85 receiving indomethacin had deteriorated compared to 19 of 85 receiving placebo, a statistically significant difference (p = 0.009). No statistically significant difference (p = 0.308) was found between tiaprofenic acid and placebo at the 7th interim analysis, the conclusion of the study. CONCLUSION: Indomethacin increased the rate of radiological deterioration of joint space in patients with OA of the knee; tiaprofenic acid did not.
Acute femoral neuropathy after renal transplantation is an uncommon and rarely recognized complication. Recovery of the nerve is usual. Although rare, five cases have come to our attention in the past twenty years. A detailed clinical and electrophysiological analysis with a six month follow-up is presented. A review of sixteen other reported cases is also provided. The possible pathophysiology including direct compression and nerve ischemia, is discussed. We believe that nerve ischemia, possibly caused by a steal phenomenon, occurs in all cases following the anastomosis of the graft renal artery to the internal iliac artery, with a superimposed component of compression in some cases. The severity of ischemia probably determines the degree of recovery.
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Seventeen patients suffering from early rheumatoid disease (mean duration, 3.5 years) and treated with nonsteroidal antiinflammatory drugs alone had evidence of systemic bone changes. Transiliac bone biopsies, compared with age and gender-matched controls, demonstrated reduced bone volume and increased eroded surface. In addition, the metacarpal indices were reduced in the rheumatoid patients and correlated with the iliac crest bone volume. These changes, found distal from sites of synovitis, suggest that in this group of rheumatoid patients there were systemic changes of bone metabolism. No biochemical abnormalities of calcium homeostasis were found. Collectively, present observations may be a reflection of the rheumatoid disease process itself.
Lornoxicam is a new non-steroidal anti-inflammatory agent (NSAID) with a similar pharmacological profile to other oxicams and a potency 10 times greater than piroxicam. A multicentre, randomised, double blind, parallel group study was undertaken to compare the efficacy and tolerance of four weeks' treatment with lornoxicam (6 mg once daily, 4 mg twice daily, and 6 mg twice daily) and placebo in patients with osteoarthritis of the hip or knee. A dose related efficacy of lornoxicam was shown by the numbers of patients in each treatment group who withdrew from the trial owing to inadequate symptom relief (12/40 (30%) receiving placebo, 6/40 (15) receiving lornoxicam 6 mg daily, 4/40 (10%) receiving lornoxicam 8 mg daily, and none receiving lornoxicam 12 mg daily). This effect was confirmed by pain relief scores, which were significantly better than placebo during treatment with lornoxicam 8 mg and 12 mg daily, the effect of 12 mg daily being significantly superior to that of 8 mg daily. Similar results were obtained from functional status scores. Mean functional index (Lequesne) scores were significantly greater than placebo only at a daily dose of 12 mg lornoxicam. Lornoxicam was generally well tolerated, though some gastrointestinal side effects were seen as has been reported with other NSAIDs. Laboratory investigations showed no evidence of drug toxicity.
Human serum contains catalase activity, which can protect alpha 1-proteinase inhibitor from inactivation by H2O2. The primary source of serum catalase is probably erythrocytic. The enzyme activity correlates with haemoglobin concentration in sera from control subjects but not in sera from patients with rheumatoid arthritis. Catalase is inactivated by oxidants, such as H2O2 and hypochlorous acid and it is suggested that the decrease in catalase/haemoglobin ratio observed in rheumatoid serum is due to oxidant stress associated with inflammation.
In a series of 23 patients, the commonest cause of accessory nerve palsy was surgical trauma at the time of lymph node biopsy. The less common causes were penetrating or blunt trauma and a few were of spontaneous onset. There was involvement of adjacent motor sensory nerves in about half of the patients. The prognosis was better following blunt trauma, stretch injuries and after a spontaneous onset. The anatomical relationships of the accessory nerve and aspects of the clinical picture and management are discussed.
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Three studies reported here have confirmed that lornoxicam is effective in osteoarthritis and the ideal dose appears to be 12 mg daily. Overall, lornoxicam appears to be a useful drug in the treatment of both osteo- and rheumatoid arthritis, from the data presently available.
Molar ratios of peptide-bound and free hydroxyproline:creatinine (OHPr:Cr) in urine were measured at 3, 6, 9, and 12 months of age in two groups of very-low-birthweight (VLBW less than or equal to 1500 g) infants. Group A (15 infants) had radiographically confirmed fractures and (or) rickets (F/R); Group B (17 infants) did not. The urinary peptide-bound OHPr:Cr ratio varied widely within groups and was greatest at three months in both groups: A = 0.81 +/- 0.45 and B = 0.55 +/- 0.32 (mean +/- SD). The ratio decreased with increasing postnatal age for each group but was not statistically different between groups throughout the study. The urinary free OHPr:Cr ratio also was greatest at age three months (A = 0.32 +/- 0.15 and B = 0.53 +/- 0.46), rapidly decreasing afterwards, and was not statistically different between groups throughout the study. We conclude that, in VLBW infants, bone turnover as indicated by the urinary peptide-bound OHPr:Cr ratio is highest during early infancy; however, the wide range of values for this ratio suggests that its use alone is not sufficient for detection of F/R in VLBW infants. The rapid decrease in free OHPr:Cr ratio is presumably related to the maturation of renal tubular function.
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Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 77 patients with rheumatoid arthritis and 30 healthy subjects. Disease activity was judged according to Ritchie's articular index to be mildly active in 31 (group 1), moderately active in 29 (group 2), and severely active in 17 patients (group 3). Plasma levels of C3d, a fragment of C3, and serum levels of C4, C3, and immune complexes were also measured. The ratios C4d/C4 and C3d/C3 were calculated. The C4d/C4 and C3d/C3 ratios and the levels of circulating immune complexes correlated with the degree of disease activity without significantly departing from linear trend and discriminated between patients with different grades of disease activity. C4d, C3d, C4, and C3 also correlated with disease activity but in a non-linear relationship. A significant correlation was found between C4d and C3d, and between C4d/C4 and C3d/C3. C4d and C4d/C4 also correlated with circulating immune complexes. These results indicate that indices of C4 and C3 activation, in particular the ratios C3d/C3 and C4d/C4, provide a sensitive assessment of disease activity in rheumatoid arthritis, and confirm the major part played by the classical complement pathway in the pathogenesis of this disease.
A dose-ranging, double-blind study of pulsed methylprednisolone in 71 patients with active classical or definite RA is reported. Single pulses of 40 mg, 500 mg or 1 g were administered during a 24-h admission. All patients benefited transiently, but only in those who received 1 g was this prolonged beyond 3 weeks. Laboratory measurements showed no significant change in any group. Significantly more patients in the 1 g group felt the treatment worthwhile than in the other groups. The drop-out rates in the 40 mg and 500 mg groups differed significantly from that seen in the 1 g group and were such that statistical analysis beyond 3 weeks was difficult to interpret. Side-effects were mild. Three patients subsequently developed avascular necrosis, one in the 1 g and two in the 40 mg groups. The study suggests that single doses of MP below 1 g are not helpful in the management of acute RA.
The response of peripheral blood lymphocytes to stimulation by mitogens such as phytohaemagglutinin (PHA) is commonly depressed in both rheumatoid arthritis and iron deficiency, and as many rheumatoid patients are anaemic with evidence of abnormal iron metabolism it is possible that the same mechanism underlies the observed suppression in both conditions. In the present study the mitogenic response to PHA of lymphocytes from three rheumatoid patients, who were also iron deficient, and two healthy controls has been shown to be significantly less in iron deficient than iron containing media (p less than 0.001). In addition, iron deficient sera from these patients reduced the PHA induced proliferation of lymphocytes from a normal subject (p less than 0.01), an effect which was prevented by prior addition of iron to these serum samples. In iron containing media lymphocytes from five patients and two controls showed no difference in their response to PHA for both the minimum mitogen concentration which enhanced transformation and the peak [3H]thymidine uptake; but patients' lymphocytes showed significantly less response to PHA concentrations of 5 and 10 mg/l (p less than 0.02), resulting in a reduction in the area under the dose response curves up to 20 mg/l (p less than 0.05). These findings show both that iron deficient sera can impair PHA induced lymphocyte transformation and that lymphocytes from iron deficient rheumatoid patients have impaired responsiveness to PHA. Iron is known to be required intracellularly for the enzyme ribonucleotide reductase, which is important for DNA synthesis, and reduced activity of this enzyme could explain these observed effects.
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