Effect of aerobic training on the host systemic milieu in patients with solid tumours: an exploratory correlative study.

BACKGROUND: Few studies have investigated the effects of exercise on modulation of host factors in cancer patients. We investigated the efficacy of chronic aerobic training on multiple host-related effector pathways in patients with solid tumours. PATIENTS AND METHODS: Paired peripheral blood samples were obtained from 44 patients with solid tumours receiving cytotoxic therapy and synthetic erythropoietin (usual care; n=21) or usual care plus supervised aerobic training (n=23) for 12 weeks. Samples were characterised for changes in immune, cytokine and angiogenic factors, and metabolic intermediates. Aerobic training consisted of three supervised cycle ergometry sessions per week at 60% to 100% of peak oxygen consumption (VO2peak), 30-45 min per session, for 12 weeks following a nonlinear prescription. RESULTS: The between-group delta change in cardiopulmonary function was +4.1 ml kg (-1) min(-1), favouring aerobic training (P<0.05). Significant pre-post between-group differences for five cytokine and angiogenic factors (HGF, IL-4, macrophage inflammatory protein-1ß (MIP-1ß), vascular endothelial growth factor (VEGF), and TNF-α) also favour the aerobic training group (P's<0.05). These reductions occurred in conjunction with nonsignificant group differences for T lymphocytes CD4(+), CD8(+), and CD8(+)/CD45RA (P<0.10). For these factors, circulating concentrations generally increased from baseline to week 12 in the aerobic training group compared with decreases or no change in the usual care group. No significant changes in any metabolic intermediates were observed. CONCLUSIONS: Aerobic training alters host availability of select immune-inflammatory effectors in patients with solid tumours; larger confirmatory studies in more homogenous samples are warranted.

Risk for transmission of Naegleria fowleri from solid organ transplantation.

Primary amebic meningoencephalitis (PAM) caused by the free-living ameba (FLA) Naegleria fowleri is a rare but rapidly fatal disease of the central nervous system (CNS) affecting predominantly young, previously healthy persons. No effective chemotherapeutic prophylaxis or treatment has been identified. Recently, three transplant-associated clusters of encephalitis caused by another FLA, Balamuthia mandrillaris, have occurred, prompting questions regarding the suitability of extra-CNS solid organ transplantation from donors with PAM. During 1995-2012, 21 transplant recipients of solid organs donated by five patients with fatal cases of PAM were reported in the United States. None of the recipients developed PAM, and several recipients tested negative for N. fowleri by serology. However, historical PAM case reports and animal experiments with N. fowleri, combined with new postmortem findings from four patients with PAM, suggest that extra-CNS dissemination of N. fowleri can occur and might pose a risk for disease transmission via transplantation. The risks of transplantation with an organ possibly harboring N. fowleri should be carefully weighed for each individual recipient against the potentially greater risk of delaying transplantation while waiting for another suitable organ. In this article, we present a case series and review existing data to inform such risk assessments.

Pregnancy rates in angus cross beef cows bred at observed oestrus with or without second GnRH administration in fixed-time progesterone-supplemented Ovsynch and CO-Synch protocols.

Crossbred cows (n = 1073) from five locations had oestrous cycles synchronized with 100 microg of GnRH IM and insertion of controlled internal drug release device (CIDR) on Day 0 followed by 25 mg of PGF(2alpha) IM and CIDR removal on Day 7. Kamar patches were placed on all cows at CIDR removal. Cows were observed three times daily for oestrus after PGF(2alpha) administration. In the Ovsynch-CIDR group, cows detected in oestrus (n = 193) within 48 h after PGF(2alpha) were inseminated using the AM-PM rule. Among these cows, 80 received and 113 did not receive a second GnRH at 48 h after PGF(2alpha). Cows (n = 345) not detected in oestrus received a second GnRH at 48 h after PGF(2alpha) on Day 9, and fixed-time AI 16 h after the GnRH on Day 10. In the CO-Synch-CIDR group, cows detected in oestrus (n = 224) within 48 h after PGF(2alpha) were inseminated using the AM-PM rule. Among these cows, 79 received and 145 did not receive a second GnRH at 64 h after PGF(2alpha). Cows (n = 311) not detected in oestrus received a second GnRH on Day 10 at the time of AI, 64 h after PGF(2alpha). The AI pregnancy rates were not different between the Ovsynch-CIDR and CO-Synch-CIDR groups (p = 0.48). There were no differences in the AI pregnancy rates for cows inseminated at a fixed time (p = 0.26) or at detected oestrus (p = 0.79) between the treatment groups. Among cows inseminated in oestrus, there were no differences in the AI pregnancy rates between cows that received or did not receive the second GnRH (p = 0.47). In conclusion, acceptable AI pregnancy rates can be achieved with or without inclusion of oestrus detection in the Ovsynch-CIDR and CO-Synch-CIDR protocols. Among cows detected in oestrus, cows that received a second GnRH yielded similar pregnancy rates when compared with cows that did not receive the second GnRH.

Microchimerism in sensitized renal patients.

BACKGROUND: Patients exposed to allogeneic human tissue sometimes produce anti-HLA antibody for many years in the absence of further obvious antigen exposure. To investigate the mechanism of sustained sensitization, we identified females awaiting renal transplantation with high panel-reactive antibody but no exposure to allogeneic tissue for at least 1 month. METHODS: We analyzed peripheral blood microchimerism using nested polymerase chain reaction amplification specific for the SRY region of the Y chromosome. RESULTS: Microchimerism was detected in 3 of 10 patients but in none of 8 normal female subjects. In two cases, the amplified DNA polymerase chain reaction product was sequenced and was confirmed to be identical to the SRY gene. The estimated level of chimerism as compared with serial dilutions of DNA from male peripheral blood leukocytes was about 1/50000. CONCLUSION: These results do not establish causality but support the possibility that antigens from microchimeric donor cells may sustain the HLA antibody response in certain patients.

Stimulation of uterine ornithine decarboxylase in organ culture by decreasing osmolality: possible relation to in vivo mechanisms.

Ornithine decarboxylase (ODC) activity increases during many growth responses. Some cells and tissues in culture also exhibit elevated enzyme activity with decreasing osmolality of the culture medium. We have found that this also occurs with uterine tissue from ovariectomized rats. Organ culture incubation under hypotonic conditions caused maximal stimulation of uterine ODC activity at 4 hr. This stimulation was observed when either NaCl or sucrose was used to adjust the osmolality. Incubation under isotonic conditions also increased ODC activity relative to hypertonic conditions. This increase was similar in magnitude to that seen with unincubated uterine tissue from animals receiving systemic estradiol or intrauterine cholera toxin. Both estradiol and cholera toxin increase vascular permeability, and the resultant edema changes the extracellular microenvironment of the uterine cells. We suggest that this change somehow is mimicked by organ culture under hypotonic or isotonic conditions and is responsible for the stimulation of uterine ODC activity.

Estrogen-like stimulation of uterine ornithine decarboxylase by cholera toxin.

Cholera toxin administered by intrauterine injection to ovariectomized rats increased uterine ornithine decarboxylase activity as much as systemic estradiol at 4 h after treatment. At 45-60 min after treatment, however, cholera toxin did not increase nuclear estrogen receptor or stimulate synthesis of the uterine "induced protein," which is closely correlated with nuclear receptor, whereas estradiol caused substantial increases in both nuclear receptor and induced protein synthesis. Intrauterine injection of cholera toxin also produced an estrogen-like elevation of the uterine protein/DNA ratio at 24 h. Because both cholera toxin and estradiol are known to increase vascular permeability, our results support the hypothesis that some uterine effects of estradiol are not mediated by receptor-genome interaction but involve another mechanism that is associated with increased vascular permeability.