A new approach to rheumatoid arthritis

Slow-acting antirheumatic drugs (SAARDs) are usually prescribed in rheumatoid arthritis only when non-steroid anti-inflammatory drugs can no longer suppress the inflammation or when articular damage is radiologically apparent. It was established recently that articular damage occurs in an early phase of RA. This damage is linked to subsequent disability; to prevent it is the purpose of SAARDs. In view of the short-term reduction of arthritis activity and improvement of function as well as the meanwhile established fact that the side effects of SAARDs are not different from those of other antirheumatic agents, SAARDs should be prescribed in an early phase of RA.     

Experimental determination of NH<Subscript>4</Subscript>NO<Subscript>3</Subscript>-KNO<Subscript>3</Subscript> binary phase diagram

The solid-state phase transitions in ammonium nitrate (AN)-potassium nitrate (KN) system, and the equilibrium AN-KN phase diagram have been determined by using differential scanning calorimetry and high-temperature in situ x-ray diffractometry. Sample preparation was performed in a special “dry room” with very low humidity. A single phase region (AN III) with no phase transitions to 373 K was observed in the composition range 5 to 20% KN; this is critical for use in air bag gas generators. The high-temperature KN phase (KN I) has a wide range of stability from 20 to 100 wt.% KN. There are one eutectic, two eutectoid, three peritectoid, and one congruent transformations in this phase diagram. Two new nonstoichiometric phases were found at lower temperatures in the mid-composition range between the AN and KN terminal solid solutions. Details of the phase equilibria are presented.     

Age-related changes in cognitive ERPs of attenuation

The purpose of this article is to deliberate the moral and legal dilemma entailed in the weapon of the labour strike as a pressure tactic on the Israeli Finance Ministry regarding job slots, budgets and, in effect, violating the collective agreement signed by the nurses and impairing patients' treatment, as opposed to refraining from striking and suffering the heavy burden of work, the lack of trained personnel, low wages, and the inability to give patients proper, high quality treatment.     

Effect of postischemic reperfusion on microcirculation and lipid metabolism of skeletal muscle

To study the effect of ischemia reperfusion injury on microvascular reactivity and tissue metabolism in skeletal muscle, a Sprague-Dawley rat cremaster muscle was prepared as a tourniquet ischemia model and subjected to 2 hr ischemia followed by 1 hr reperfusion to simulate the timing of ischemia during microvascular surgery. The dose-response curve of arteriolar reactivity to norepinephrine, lipid peroxidation, and ultrastructure of capillaries was determined in both the control and postischemic reperfusion stages. Judging from the results, we summarize our observations as follows: (1) Postischemic reperfusion significantly increased arteriolar reactivity to norepinephrine, in which the EC50 for vasoconstriction decreased in all three orders of arterioles. These results suggest that reperfusion could have impaired the vasodilation control mechanism, possibly being endothelium dependent. (2) Lipid peroxidation increased sixfold in the reperfusion group, suggesting that oxygen free radicals have produced significant tissue damage under the created conditions. (3) Significant endothelial damage in the capillaries shown by electron microscope observation supports these studies, indicating that ischemia/reperfusion in clinically transplanted skeletal muscles could cause significant damage to the tissue microcirculation both physiologically and metabolically.     

Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Composite finger metacarpophalangeal joint reconstruction in combined second and third free toe-to-hand transfers

Composite metacarpophalangeal joint reconstruction using the toe proximal phalanx and the metacarpal head, with a capsular repair, is an option during free toe transfer procedures for absent fingers. Eleven composite metacarpophalangeal finger joint reconstructions were performed in four patients concurrent with combined second and third toe-to-hand transfer. The average follow-up period was 5 years. Postoperative assessment included range of motion, stability, radiographic changes, and pain. The average range of motion was 52 degrees, average ulnar stress deviation was 14 degrees. No patients complained of pain. Composite metacarpophalangeal joint reconstruction should be considered in free toe-to-hand procedures when metacarpal head articular cartilage is preserved.