Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial

OBJECTIVE: To assess the efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis (RA). METHODS: At the start of their initial treatment with a disease-modifying antirheumatic drug (DMARD), patients with early (duration < or =1 year) active RA were randomly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years. Radiographs of the hands and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde. Remission was defined as a Disease Activity Score in 28 joints of <2.6. Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years. RESULTS: Of the 250 patients included, 242 completed the study and 225 had radiographs available both at baseline and at 2 years. At 2 years, the median and interquartile range (IQR) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group (1.8 [IQR 0.5-6.0] versus 3.5 [IQR 0.5-10]; P = 0.019). In the prednisolone group, there were fewer newly eroded joints per patient after 2 years (median 0.5 [IQR 0-2] versus 1.25 [IQR 0-3.25]; P = 0.007). In the prednisolone group, 25.9% of patients had radiographic progression beyond the smallest detectable difference compared with 39.3% of patients in the no-prednisolone group (P = 0.033). At 2 years, 55.5% of patients in the prednisolone group had achieved disease remission, compared with 32.8% of patients in the no-prednisolone group (P = 0.0005). There were few adverse events that led to withdrawal. Bone loss during the 2-year study was similar in the 2 treatment groups. CONCLUSION: Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA, provided a high remission rate, and was well tolerated. Therefore, the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA.     

Measurements of cardiac output and organ blood flow in rats using 99Tcm labelled microspheres.

The cardiac output and regional blood flow have been simultaneously determined in the anesthetized rat by using the reference organ method. 99Tcm labelled dextran 15 micron microspheres were injected in the left ventricle while simultaneously an arterial reference sample was drawn at constant known rate. The values calculated regarding cardiac output agree well with previously recorded series. Regional organ blood flow in the rat is presented as ml . min-1 . g-1 tissue and values do agree with those reported by others. The results indicate that the reference organ method can be used in the rat for the study of cardiac output and regional blood flow.     

A comparison between hepatic artery ligation and portal 5-Fu infusion versus 5-Fu intra arterial infusion for colorectal liver metastases.

AIM: A prospective randomized study was executed comparing two regimens of regional therapy for liver metastases from colorectal cancer. METHODS: Eighteen patients were allocated to hepatic artery occlusion for 16 h followed by intraportal 5-fluorouracil (5-Fu) infusion (1000 mg/m(2)) for 5 days every sixth week (HAO). Twenty-one patients received intra-arterial 5-Fu infusion+Leucovorin (100 mg) i.v. for 2 days every second week (HAI). The follow up every third month included CT and CEA. Thirteen patients had limited extrahepatic cancer. At tumor progression regional therapy was stopped and systemic chemotherapy or the best supportive care was administered. RESULTS: The study was discontinued after randomization of 39 patients. No significant difference in survival within patients with and without extrahepatic cancer was present. The mean survival was longer in the HAI group than for the HAO group (19 months versus 13 months, p=0.0147) (median 18 (8-37) versus 12 (2-26). PR and SD were registered in 8/18 in the HAO group and 17/21 patients in HAI group. The median time to progress was 4 (1-22) months versus 7 (1-23) months for the HAO and HAI group, respectively. CONCLUSION: Regional intraarterial infusion with 5-Fu gives significantly better survival than hepatic artery occlusion followed by portal infusion. A limited amount of extrahepatic cancer does not influence survival time. A trial comparing hepatic artery 5-FU infusion and Leucovorin versus the most effective systemic therapy is warranted.     

Actions of sulphasalazine and its metabolites on polymorphonuclear leucocyte superoxide

In recent years, interest has been focused on the possibility that sulphasalazine (SASP), which is used in the treatment of both rheumatoid arthritis and inflammatory bowel disease, may act by inhibition of PMN Superoxide generation and/or by scavenging of reactive oxygen products. In this article, we summarize our own studies in this field and discuss our findings in relation to other reports on the same subject. It is evident that SASP and SP, in vitro, inhibit PMN Superoxide production elicited by receptor-mediated stimuli and a calcium ionophore, and that this effect seems to be dependent on inhibition of intracellular Ca²⁺ mobilization. 5-Aminosalicylic acid (5-ASA), on the other hand, excerts its effects by scavenging oxygen free radicals.     

Effects of antirheumatic treatment on gastric secretory function and salivary flow in patients with rheumatoid arthritis.

Many patients with rheumatoid arthritis have impaired gastric acid secretion and dysfunction of the lacrimal and salivary glands, conditions which have been proposed to be due to glandular atrophy. The hypothesis that the rheumatoid inflammation by itself has a depressive effect on these secretory functions was tested on 20 patients with active rheumatoid arthritis who underwent 16 weeks of sulphasalazine therapy. The patients responded well to the treatment, with reduction of joint indices and acute phase reactants. The resting and stimulated whole salivary secretion rate increased in 9/10 and 8/10 patients, respectively. The maximal gastric acid output increased in those patients who had a moderate reduction in acid output prior to treatment. When estimated by s-pepsinogen I, the gastric secretory capacity increased in all patients but one. In a group of auranofin treated patients, s-pepsinogen I rose only in those who responded to treatment with reduced disease activity. These results support the idea that the impaired secretory functions are at least partially reversible and probably also partly inflammatory mediated.     

Relation to chemotactic factor gradients to neutrophil migration and orientation under agarose

Chemotactic substances confer a migratory pattern for neutrophil granulocytes under agarose that is characteristic for each agent. To analyse the cause of such differences, we have studied neutrophil migration and orientation with f-Met-Leu-Phe (fMLP), leukotriene B4 (LTB4), and serum as chemoattractants. When these agents were used at optimal concentrations, it was observed that cells stimulated by LTB4 did not start migration as fast and did not migrate as far as those exposed to fMLP, but they maintained a higher degree of orientation. This delay in initiation of migration and maximal degree of orientation was even more marked when serum was the chemoattractant. These migration variables were related to the generation of gradients in the agarose of fML[3H]P, arachidonic-[3H]acid (AA, of which LTB4 is a metabolite), and fluorescein. The curvilinear AA gradient was flatter and more stable than those of fML[3H]P and fluorescein, which were linear. Thus, differences in the development and shape of the gradient of chemoattractant may contribute to differences in migration kinetics.     

Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids

Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of total body microwave hyperthermia and hepatic artery ligation on liver tumors--an experimental study in rats

The effect of general microwave hyperthermia and hepatic artery ligation (HAL) was tested on Wistar rats with a transplanted N-methyl-N-nitrosoguanidine-induced adenocarcinoma in the liver. Total body hyperthermia (41.5 degrees C for 1 hour, three times during 24 hours) was given on the same day as HAL, and 1, 2, and 3 days after. HAL induced a slower tumor growth than untreated controls. No additive effect was registered when total body microwave hyperthermia was added to HAL. When hyperthermia was added 2 days after HAL, there was a transient decrease in tumor volume as in the HAL series. Total body microwave hyperthermia added 3 days after HAL induced a faster tumor growth than after HAL alone. When hyperthermia was added the same day and 1 day after HAL, there was a 50% mortality.     

Idiosyncratic compensation of the subjective visual horizontal and vertical in 60 patients after unilateral vestibular deafferentation

OBJECTIVE: To investigate long-term compensation mechanisms of utricular function after translabyrinthine surgery for vestibular schwannoma. Correlations between the subjective visual horizontal (SVH) and subjective visual vertical (SVV) and other parameters of vestibular compensation were studied. The correlation between the SVH and SVV was also investigated to see whether these measurements are compatible for patients. MATERIAL AND METHODS: Sixty consecutive patients were investigated 3 months before and 6 months after surgery by means of electronystagmography and SVH and SVV tests. Tumor size was measured using MRI. RESULTS: The SVH and SVV increased significantly towards the ipsilesional side postoperatively. Preoperative tilt correlated with age. Postoperative tilt correlated weakly with preoperative caloric sensitivity and inversely with tumor size. The correlation between the SVH and SVV was high both before and after surgery (r(s) > 0.74; p < 0.001). CONCLUSIONS: The long-term compensation of static tilt perception was dependent on age and not on dynamic canal functions. We propose an idiosyncrasy in the SVH and SVV compensation after unilateral vestibular deafferentation, incongruous with the general course of vestibular compensation. The results suggest a probable dependence on non-vestibular information, i.e. proprioception, in facilitating compensation of static vestibular deficits. The similarity between the SVH and SVV measurements confirms that either test can be used clinically for patients with vestibular lesions.