Monocyte activation in rheumatoid arthritis (RA): increased integrin, Fc gamma and complement receptor expression and the effect of glucocorticoids.
(9/2898)
The aim of this work was to study the expression of beta 1- and beta 2-integrins, CR1, CD44 and Fc gamma receptors on peripheral blood monocytes in RA. The expression of these receptors was measured by flow cytometry, before and after treatment with low-dose prednisolone. Expression of the same receptors was also measured before and after treatment with metyrapone, a substance that inhibits the synthesis of cortisol in the adrenals. The expression of the beta 2-integrins CD11a, CD11b and CD18, of CD35 (CR1), and of Fc gamma RII and Fc gamma RI (CD32 and CD64) on monocytes was elevated in the RA patients compared with healthy controls, while the expression of the beta 1-integrins (CD29, CD49d, CD49f) was unaffected. A significant correlation between monocyte expression of CD64 and C-reactive protein (CRP), and blood platelet count, respectively, was found in the group of patients with RA. After 4-6 weeks of treatment with low-dose prednisolone, the expression on the monocytes of CD11a, CD11b, CD18, CD35, CD32 and CD64 was normalized. A significant correlation (r = 0.64, P = 0.02) was found between the decrease in expression of CD11b and clinical improvement after prednisolone treatment. Two days of metyrapone treatment, which significantly lowered the serum cortisol levels, elevated the expression of CD35 and CD49f. Priming of peripheral monocytes seems to be one of the mechanisms behind the recruitment of monocytes to the rheumatoid synovium. One reason for the good clinical effects of prednisolone in RA could be a down-regulation of adhesion and phagocytosis receptors on monocytes. (+info)
Pathogenesis and treatment of HTLV-I associated myelopathy.
(10/2898)
That HTLV-I is not a latent infection is indicated by the detection of mRNA in the peripheral blood and CNS of patients with HTLV-I infection and by the persisting humoral and cellular immune responses. Indeed the frequency of anti-HTLV CTL is extremely high. The reduction in anti-TAX CTL frequency following reduction in proviral load suggests that removal of viral antigen may result in a reduced inflammatory response at least in peripheral blood and although the clinical data should be interpreted with caution, perhaps in the CNS. Patients with more advanced disease, and possibly fixed deficits may not benefit from either anti-inflammatory or antiretroviral treatment. The patients with most to gain are those with least deficit in whom early diagnosis and treatment will depend on raising awareness of HTLV-I beyond the neurological community. Many patients with HAM first present to a urologist or gynaecologist with bladder dysfunction or may have been seen in the genitourinary clinical with impotence or positive treponemal serology, which in the older patient is often the result of childhood infection with Treponema pallidum pertenue. Investigation of these patients should include HTLV-I serology and further investigation of HTLV-I positive patients should include proviral load measurements as well as markers of inflammation. Treatments whether antiviral or anti-inflammatory should be assessed for their effect on both as well as a clinical response. (+info)
Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids. Asthma and Allergy Group.
(11/2898)
BACKGROUND: Patients with difficult asthma suffer chronic moderate to severe persistent asthma symptoms despite high doses of inhaled and oral corticosteroid therapy. These patients suffer a high level of treatment and disease related morbidity but little is known about the degree of airway inflammation in these patients. METHODS: Fifty two patients were examined to assess levels of exhaled nitric oxide (NO) as a surrogate marker of inflammatory activity in this condition. From this group, 26 patients were defined with severe symptoms and current physiological evidence of reversible airway obstruction requiring high dose inhaled (> or = 2000 micrograms beclomethasone dipropionate (BDP) equivalent) or oral steroid therapy to maintain disease control. RESULTS: Exhaled NO levels were higher in subjects with difficult asthma (mean 13.9 ppb, 95% CI 9.3 to 18.5) than in normal controls (7.4 ppb, 95% CI 6.9 to 7.8; p < 0.002), but lower than levels in steroid naive mild asthmatics (36.9 ppb, 95% CI 34.6 to 39.3; p < 0.001). Prednisolone treated patients had higher exhaled NO levels than patients only requiring inhaled corticosteroids (17.5 ppb, 95% CI 11.1 to 24.0 versus 7.2 ppb, 95% CI 4.6 to 9.8; p = 0.016), suggesting greater disease severity in this group. Non-compliance with prednisolone treatment was observed in 20% of patients but this did not explain the difference between the treatment groups. Exhaled NO levels were closely correlated with symptom frequency (p = 0.03) and with rescue beta agonist use (p < 0.002), but they did not correlate with lung function. CONCLUSIONS: Exhaled NO may serve as a useful complement to lung function and symptomatology in the assessment of patients with chronic severe asthma, and in the control and rationalisation of steroid therapy in these patients. (+info)
Glucocorticoid insensitive asthma: a one year clinical follow up pilot study.
(12/2898)
BACKGROUND: Glucocorticoid resistant or insensitive asthmatic subjects are usually defined as patients whose baseline pre-bronchodilation forced expiratory volume in one second (FEV1) of less than 70-80% predicted improves significantly in response to beta 2 agonists but by less than 15% following 1-2 weeks of 40 mg prednisolone daily. Since there is little long term clinical information on these patients, a one year prospective study was performed to assess whether glucocorticoid sensitivity may vary over time. METHODS: Nineteen severe asthmatic subjects were studied and received 40 mg prednisolone daily for seven days. Prednisolone was given for a further seven days in glucocorticoid insensitive asthmatics and then stopped. Patients were followed up for one year and the glucocorticoid test was repeated on five patients in each group six months later. RESULTS: Eleven patients were classified as glucocorticoid insensitive and eight as glucocorticoid sensitive on day 7. The demographic characteristics of the patients were similar in both groups. Four glucocorticoid insensitive patients became responsive after one further week of prednisolone treatment. Six months later, four of five glucocorticoid sensitive patients and three of five previously glucocorticoid insensitive patients were glucocorticoid sensitive. CONCLUSIONS: Glucocorticoid sensitivity varies over time. (+info)
Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn's disease.
(13/2898)
BACKGROUND: Crohn's disease is a chronic inflammatory disease of the alimentary tract. Azathioprine is an effective agent in the management of chronic active Crohn's disease leading to long term remission of disease activity. Such treatment leads to limited efficacy or side effects in a small subset of patients. AIMS: To compare efficacy and side effects of treatment with azathioprine plus corticosteroids versus mycophenolate mofetil (MMF) plus corticosteroids in patients with chronic active Crohn's disease. METHODS: Seventy patients with chronic active Crohn's disease (Crohn's disease activity index (CDAI) greater than 150) were randomised for treatment with azathioprine/cortisone or MMF/cortisone. Corticosteroid dosage was tapered according to a standard protocol. Disease activity was monitored by clinical scores after one, two, three, and six months. RESULTS: Treatment of patients with moderately active (CDAI 150-300) Crohn's disease with MMF/cortisone led to a significant reduction in clinical activity scores comparable to treatment with azathioprine/cortisone. Treatment of patients with highly active Crohn's disease (CDAI greater than 300) with MMF/cortisone caused significant suppression of clinical activity earlier than azathioprine/cortisone treatment. Treatment with MMF/cortisone was associated with few adverse effects. CONCLUSION: Treatment of chronic active Crohn's disease with MMF plus cortisone appears to be effective and well tolerated and should be considered in patients allergic to azathioprine or in whom azathioprine has failed. (+info)
Pneumonitis secondary to the influenza vaccine.
(14/2898)
We report a 58-year-old man who developed respiratory distress and interstitial shadowing on chest X-ray 10 days after receiving the influenza vaccine. He failed to respond to intravenous antibiotics but his clinical condition, hypoxia and chest X-ray changes improved dramatically on oral steroids. The clinical diagnosis was pneumonitis secondary to recent influenza vaccination. (+info)
Prospective evaluation for upper gastrointestinal tract acute graft-versus-host disease after hematopoietic stem cell transplantation.
(15/2898)
The incidence and clinical significance of upper gastrointestinal tract acute graft-versus-host disease (upper GI GVHD) were prospectively evaluated in 44 Japanese patients who underwent allogeneic (n = 26) or autologous (n = 18) stem cell transplantation. Endoscopic examination was routinely performed between days 20 and 50 post-transplant and when symptoms of upper GI and/or acute GVHD of other organs were present. The results were compared with the historical records of 49 allograft and 20 autograft recipients. The diagnosis of upper GI GVHD was confirmed by histologic findings of GVHD and persistent upper GI tract symptoms. The incidence of upper GI GVHD was 46% in the prospective allograft group, higher than in the retrospective group. Upper GI GVHD was not diagnosed in any autograft patients. Twelve of 19 patients with upper GI GVHD had skin GVHD, and two of the 12 had concurrent lower GI GVHD. Upper GI GVHD was successfully treated with steroids and did not progress to symptomatic lower GI GVHD. In addition, upper GI GVHD completely resolved without specific alteration in immunosuppressant therapy in six patients. No risk factors for upper GI GVHD could be identified. The presence of upper GI GVHD did not significantly affect early death rate, incidence of chronic GVHD, and overall survival. In conclusion, by the prospective evaluation of the upper GI tract by endoscopy we could accurately diagnose upper GI GVHD in half our allogeneic recipients. However, upper GI GVHD was successfully controlled with or without additional steroids in all cases and had little impact on transplant outcome. (+info)
Effects of a phosphate buffered extracellular (Ep4) solution in preservation and reperfusion injury in the canine liver.
(16/2898)
The Ep4 solution, a phosphate buffered extracellular-type solution, is effective in canine lung transplantation following a 96-hour hypothermic (4 degrees C) preservation. In this experiment, we used this solution for liver preservation followed by transplantation. We compared the Ep4 solution with the lactated Ringer's (LR) and the Collins' M (CM) solution (a phosphate buffered intracellular-type solution) in two studies, 1) 48-hour liver preservation, and 2) orthotopic liver transplantation after 5-hour preservation. In the preservation study, purine nucleoside phosphorylase (PNP) levels as a marker of endothelial damage, and alanine aminotransferase (ALT) levels were significantly lower in the livers immersed into the Ep4 solution than in those immersed into other solutions at 36 and 48 hours after preservation. Microscopically, the endothelial injury occurred 24 hours after preservation in the CM solution, and 36 hours after preservation in the LR and Ep4 solutions. In the transplantation study, serum PNP and ALT levels in the livers immersed in Ep4 solution showed a lower tendency compared with those in other solutions at the time of reperfusion, but the histological differences among three groups were not apparent. The present study suggests that the liver can be stored better for a longer time using Ep4 solution than using LR and CM solutions. (+info)