Lower limb vasodilatory capacity is not reduced in patients with moderate COPD

We compared exercise capacity (peak O₂ uptake; V̇O_2peak) and lower limb vasodilatory capacity in 9 patients with moderate COPD (FEV₁ 52.7 ± 7.6% predicted) and 9 age-matched healthy control subjects. V̇O_2peak was measured via open circuit spirometry during incremental cycling. Calf blood flow (CBF) measurements were obtained at rest and after 5 minutes of ischemia using venous occlusion plethysmography. While V̇O_2peak was significantly lower in the COPD patients (15.8 ± 3.5 mL·kg⁻¹·min⁻¹) compared with the control group (25.2 ± 3.5 mL·kg⁻¹·min⁻¹), there were no significant differences between groups in peak CBF or peak calf conductance measured 7 seconds post-ischemia. V̇O_2peak was significantly correlated with peak CBF and peak conductance in the control group, whereas no significant relationship was found between these variables in the COPD group. However, the rate of decay in blood flow following ischemia was significantly slower (p < 0.05) for the COPD group (−0.036 ± 0.005 mL·100 mL⁻¹·min⁻¹·s⁻¹) when compared with controls (−0.048 ± 0.015 mL·100 mL⁻¹·min⁻¹·s⁻¹). The results suggest that the lower peak exercise capacity in patients with moderate COPD is not related to a loss in leg vasodilatory capacity.     

Plasma lipids in kidney transplanted children and adolescents: influence of pubertal development, dietary intake and steroid therapy

Abstract. Plasma triglycerides and/or cholesterol were significantly increased in twenty-four of thirty kidney transplanted children and adolescents with stable renal function, at least one year after the last rejection crisis who received low dose prednisone therapy. The cholesterol increment was related to both low density and high density lipoproteins. However, similar to findings in adult allograft recipients, these increases were very variable: six subjects had normal levels, eight had increased triglycerides, five increased triglycerides and cholesterol, and eleven increased cholesterol. No influence of renal function was found in this series of patients all of whom had plasma creatinine below 160 μmol/1. Subjects who had achieved sexual development had lower cholesterol values. An insignificant difference was observed between patients receiving daily and alternate-day steroid therapy, but a significant negative correlation was found between plasma triglycerides and fractional urinary excretion of 17 OH corticosteroids in the first 6 h after an oral dose of prednisone. Finally, no correlation was found between energy intake and triglycerides; but a significant correlation was observed between protein intake and plasma cholesterol.
In conclusion, some patients show a high level of triglycerides and/or cholesterol after renal transplantation, possibly due to a different individual response to steroid therapy.     

Do men undergoing sterilizing cancer treatments have a fertile future?

This study was designed to assess the effect of cancer treatments on the natural and assisted reproductive potential of men. A cohort of men with cancer, in whom radiotherapy and/or chemotherapy was planned, were invited to participate. Twenty-two pre- and post-treatment semen samples were analysed. The reproductive potential of participants was assessed with respect to the current range of fertility treatment options available. Abnormal sperm concentrations were found in 27% of patients pre-treatment compared to 68% post-treatment following a mean latency of 20 months from treatment. Fifty-nine percent of patients experienced a clinically significant decrease in sperm, concentration following radiotherapy and/or chemotherapy; 23% developed azoospermia following treatment. Eighty-two percent of patients with testicular malignancy had oligo- or azoospermia post-treatment. Only one patient had a clinically significant reduction in the percentage of motile spermatozoa post-treatment. Cryopreservation of semen prior to treatment improved the fertility prospects of 55% of patients. Intracytoplasmic sperm injection (ICSI) enhanced the fertility prospects of a further 14%. In the absence of, or after depletion of, cryopreserved semen, ICSI could enhance the fertility prospects of 45% of patients. Fertilization has been achieved by ICSI using spermatozoa retrieved by testicular biopsy from an azoospermic testicular cancer survivor 8 years after chemotherapy. It was concluded that chemotherapy and/or radiotherapy may depress semen concentration to the extent of rendering a man infertile. The severity of the reduction in sperm concentration following treatment is unpredictable but likely to be most severe in those with testicular malignancy and those treated with radiotherapy or alkylating chemotherapy agents. Not all men are keen to undergo an appraisal of their post-treatment fertility potential, for reasons which are unclear. Improving awareness and education of patients concerning the effects of both cancer and cancer treatments on reproductive potential is essential. With the advent of ICSI, it is possible to offer a very reasonable chance of conception in all men with cancer who present for cryopreservation of semen prior to treatment in whom spermatozoa (even in very low concentrations) are present in the ejaculate.      

Cloning and characterization of the guinea pig C5a anaphylatoxin receptor: interspecies diversity among the C5a receptors

The anaphylatoxin C5a receptor (C5aR, CD88 in man) plays a prominent role in mediating inflammatory and host defense processes. Direct evidence of C5aR involvement in host defense mechanisms was demonstrated recently using C5aR knockout mice. Mice deficient in C5aR were unable to clear intrapulmonary-instilled bacteria. The guinea pig system is perhaps unique for exhibiting cross-reactivity with human complement components and its high sensitivity to anaphylatoxins. Therefore, we cloned the guinea pig C5aR from a megakaryocyte cDNA library. The deduced amino acid sequence of guinea pig C5aR is 67% identical to human, 61.6% to dog, 60.2% to mouse and 63.6% to rat C5aR. Transient expression of guinea pig C5aR in COS-7 cells and stable expression on L cell fibroblasts were confirmed by FACS analysis. Competitive binding studies using [125I]C5a and stimulation of calcium mobilization by C5a proved that functional C5aR was expressed on these stably transfected L cells. The N-terminal extracellular region of guinea pig C5aR was five to seven residues shorter than the same region in C5aR from other species and sequence homology was limited to 11%. Other outer membrane loops were also poorly conserved (8-33%) when compared across five species. Transmembrane segments were highly conserved between these various species (46-86%). Guinea pig C5aR binds human C5a, therefore residues critical for C5a binding have been conserved between these species. Sequence comparison of C5aR from multiple species permits conserved elements of the ligand binding sites to be elucidated.