Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour.

Engineering of a variety of rodent tumour cells to secrete either interleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to reduce their tumorigenicity. However the mechanisms of action of secreted IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 had reduced growth rate and in some cases was rejected by syngeneic animals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immunohistochemical analysis of tumour nodules undergoing regression showed stimulation of a largely lymphocytic infiltrate by IL-2 and a macrophage and granulocyte infiltrate, with a small number of lymphocytes by IL-4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines might mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixed, unmodified FS29 cells. The loss of cytokine secreting cells from such admixtures occurred more rapidly for IL-2-secreting cells. Injection of IL-4-secreting, but not IL-2-secreting FS29 cells could protect mice from a delayed challenge with unmodified FS29 cells. These data suggest that IL-4 secretion stimulates the better long-term host anti-tumour response.     

Synthesis, chemical, and biological properties of vinylogous hydroxamic acids: dual inhibitors of 5-lipoxygenase and IL-1 biosynthesis.

Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.     

Muscle hypertrophy in men and women

It is widely believed that women experience less skeletal muscle hypertrophy consequent to heavy-resistance training than men. The purpose of this study was to test this hypothesis using both traditional indirect indicators as well as a direct measure of muscle size. Seven male experimental (ME), 8 female experimental (FE), and 7 control subjects were studied before and after a 16-wk weight training program, in which ME and FE trained 3 days.wk-1 at 70 to 90% of maximum voluntary contraction using exercise designed to produce hypertrophy of the upper arm and thigh. Strength increased significantly (P less than 0.05) in ME and FE, respectively, on elbow flexion (36.2 and 59.2%), elbow extension (32.6 and 41.7%), knee flexion (12.8 and 24.4%), and knee extension (28.8 and 33.9%) tests. Absolute changes were significantly greater in ME than FE in 2 of the 4 tests, whereas percentage changes were not significantly different. Substantial muscle hypertrophy occurred in the upper arms of both ME and FE as evidenced by significant increases in upper arm circumference (7.9 and 7.9%), bone-plus-muscle (B+M) cross-sectional area (CSA) estimated by anthropometry (17.5 and 20.4%), and muscle CSA determined from computed tomography scanning (15.9 and 22.8%). Changes by ME and FE were not significantly different, except for the absolute increase in estimated B+M CSA, which was significantly greater in ME (11.2 vs 7.4 cm2). No muscle hypertrophy occurred in the thigh of either ME and FE as evidenced by non-significant changes in thigh circumference (1.7 and 2.3%), B+M CSA (4.9 and 6.1%), and muscle CSA (2.9 and 2.9%). Changes by ME and FE in body weight, fat-free weight, and fat weight were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improving recovery following cardiac surgery: a randomized clinical trial*

To enhance individual and family health during recovery from heart surgery, this study employed nursing interventions based on self-efficacy and family stress theory during the hospitalization period and for 3 months thereafter. The effectiveness of the interventions were assessed through a randomized trial in which 67 prospective bypass and valve surgery patients, aged 30-77 years, and their spouses, were allocated either the experimental interventions or usual care and followed for 6 months. At 3 months post-surgery, the only statistically significant differences between the experimentals and controls were on perceived self-efficacy for lifting and tolerating emotional distress. At 6 months no significant differences were found on individual or family measures. Analyses revealed that age, gender and preoperative cardiac status significantly affected individual recovery. The study is continuing with a larger sample in order to explicate the recovery process and to better determine whether a low intensity nursing intervention can effect changes in individual and family recovery.     

Directional instability of rear caster wheelchairs

Although less common than conventional front caster wheelchairs, rear caster wheelchairs are still in use for several reasons. Many people find manual rear caster wheelchairs easier to maneuver indoors at slow speeds. This is especially true when the user attempts to maneuver the wheelchair very close to an object, such as a table. Electric wheelchairs often have rear casters to accommodate for front wheel drive. If the larger drive wheels are located at the front of the wheelchair, obstacles such as a curb can be negotiated much more easily. However, a major disadvantage of rear caster wheelchairs is that they are generally known to be directionally unstable, especially at high forward speeds. This paper presents the results of a study to determine specific measures that can be employed to improve the stability of this type of wheelchair. The instability of rear caster wheelchairs is due primarily to road forces that act on the tires when the wheelchair is displaced from its line of motion by a bump or other irregularity in the road surface. The paper discusses the experimental investigation of these road forces as well as a dynamic model used to study the instability problem. The results of a computer simulation program used to perform a parametric study of different design variables are discussed. Center of gravity position, caster trail distance, and caster pin friction are found to have a dominant influence on rear caster wheelchair directional control. Several simple but significant design recommendations are presented.     

Steroid trials in the assessment of reversibility of air flow limitation: a survey of current clinical practice of chest physicians

To evaluate how steroid trials are currently used in the assessment of reversibility of air flow limitation, a postal questionnaire was sent to 355 consultant members of the British Thoracic Society working in England and Wales; 253 questionnaires were returned (71% response rate). Two respondents did not undertake steroid trials; of the remaining 251, 75% prescribed 30-40 mg oral prednisolone, with the commonest treatment period being 2 weeks. A high dose steroid inhaler was sometimes used as an alternative by 31% of respondents. Although 71% of respondents made lung function measurements on several occasions before starting steroids and 76% made measurements during treatment, 78% assessed patients on only one occasion at the end of the trials to ascertain its outcome. Weight, blood pressure and glycosuria were measured less frequently after the steroid treatment compared to the pre-trial period. Blood glucose and serum electrolytes were infrequently measured both before and after treatment. Wide variations exist in steroid trial regimens and current practice may neither provide definitive evidence of treatment benefit nor an adequate safeguard for patients against potential side-effects.