Physiologic responses to running with a jogging stroller.

The purpose of this study was to assess the effect of running with a jogging stroller (JS) on oxygen consumption (VO2), heart rate (HR), and rating of perceived exertion (RPE). This study included 2 parts: Part 1 involved participants (N=15) running on an indoor track and Part 2 involved participants (N=12) running on a paved greenway. All participants completed 6, one-mile trials randomized over 2 visits: 3 were completed at a predetermined pace (160.8 m·min (- 1)) without a JS (NoJS), with 11.36 kg in the JS (JS1), and 22.72 kg in the JS (JS2) and 3 were self-paced and included NoJS, JS1, and JS2. VO2 and HR were measured using a portable metabolic system and telemetry. Repeated measures ANOVAs were used to determine differences among conditions. Part 1, there were no differences in VO2 across conditions, but HR and RPE were significantly higher (P<0.05) during the JS trials compared to the NoJS trials. Part 2, VO2 and RPE during JS trials were higher than NoJS trials (P<0.05). No significant differences were found in HR. The results indicate that it is feasible to run while pushing a JS with minimal increases in exertion compared to running without a JS.

Has the efficacy of penile arterial by-pass surgery in the treatment of arteriogenic erectile dysfunction been determined?

The evaluation of the efficacy of penile arterial by-pass surgery (PABG) must be based on data obtained in clinical trials which have utilized a traditionally acceptable scientific design. A review of the studies which have presented the PABG surgical outcomes analysis revealed that patient selection and patient assignment have not been randomized. Demographic and individual variables, which could potentially influence outcomes, have not been eliminated by use of a marched pair design. Treatment options, including an option which allows assessment of effect of surgery per se, have not been presented in any of the studies. A majority of the studies have not blinded the researcher who analyzed the results. Commonly, follow-up evaluations have been limited and have not used converging sources of evidence. Practical suggestions are offered to improve future clinical trials so that the question of the efficacy of PABG surgery can be scientifically answered.

Bradykinin augments the in vitro migration of nonsensitized lymphocytes.

Bradykinin and related peptides have been considered important as mediators of acute inflammation, but their role in the cell-mediated immune response has not been extensively investigated. We have examined the effect of physiological concentrations of these autacoids on the migration of nonsensitized lymphocytes employing an in vitro micropore filter assay system. Bradykinin at a concentration of 0.01-1 nM significantly stimulated the migration of both human peripheral blood and rat splenic lymphocytes. Related naturally-occurring kinins (kallidin, MetLys-bradykinin, desArg9-bradykinin) had a similar effect but other autacoids (angiotensins I and II, histamine, serotonin) were inactive. Bradykinin was more active on freshly harvested lymphocytes than on cells incubated for up to 48 h with or without mitogen. Bradykinin appeared to act predominantly as a chemokinetic agent (augmenting random nondirectional motility), as determined by checkerboard analysis. Bradykinin appeared to exert its effect on lymphocytes predominantly through the B1 class of bradykinin receptors. The migratory response to bradykinin could not be attributed to the release of arachidonic acid metabolites, but stimulated migration could be significantly inhibited by the histamine type 2 receptor antagonist cimetidine. These studies provide a novel mechanism whereby nonsensitized lymphocytes may be recruited to sites of delayed-type hypersensitivity reactions.

Rat lymphokines control the migration of nonsensitized lymphocytes.

We investigated whether mediators released from rat splenic mononuclear cells could control the in vitro migration of nonsensitized resting rat lymphocytes. Rat splenocytes stimulated with concanavalin A, other mitogens, or histamine release three lymphokines that alter rat lymphocyte migration. A positive chemokinetic factor, termed lymphocyte chemoattractant factor (LCF), has a molecular weight (MW) between 50 and 70 kDa. Two negative chemokinetic lymphokines can also be identified; lymphocyte migration inhibitory factor (LyMIF, MW 25-45 kDa) and a high MW inhibitor (HWMI, MW greater than 70 kDa). Lymphokines were destroyed by heat as well as by treatment with neuraminidase and trypsin. The action of LCF and LyMIF was prevented by phenylmethylsulfonylfluoride, a specific serine esterase inhibitor, and the action of LyMIF was also blocked by alpha-L-fucose. The discovery of these mediators provides the opportunity to study the importance of such chemokinetic lymphokines in animal models of disease.

Lymphocyte chemokinetic factors derived from human tonsils: modulation by 1,25-dihydroxyvitamin D3 (calcitriol).

Although interleukin (IL)-2 may in part be responsible for lymphocyte accumulation to sites of active sarcoidosis, other cytokines that control such recruitment are not well characterized. Similarly, the pathogenic rationale for the ability of sarcoid macrophages to produce 1,25-dihydroxycholecalciferol (calcitriol) is not understood. We studied the release of chemokinetic lymphokines from human nylon wool-non-adherent tonsillar lymphocytes (HNTLs) employing a standard in vitro lymphocyte migration assay. If mitogen-stimulated HNTL supernatants were fractionated by high-performance liquid chromatography, five positive and one negative chemokinetic factors could be identified. The five lymphocyte chemoattractant factors (LCFs) ranged in mol wt from 5 to 35 kD and stimulated the in vitro migration of nonsensitized human lymphocytes by 200 to 500%. The LCFs appeared distinct from IL-2, IL-1, or gamma-interferon. Co-incubation of HNTLs with mitogen and 1 nM calcitriol prevented the production or release of two of the LCFs and significantly decreased the quantity of a third LCF. Calcitriol also resulted in the appearance of a second negative chemokinetic factor, lymphocyte migration inhibitory factor (LyMIF). Combined with our previous studies demonstrating that calcitriol interferes with IL-2-induced lymphocyte migration, these results provide a rationale for an anti-inflammatory role for calcitriol in sarcoidosis and other granulomatous disorders. These experiments also demonstrate that the control of lymphocyte recruitment to inflammatory foci is multifactorial.