Lars Slørdal

Reversal of sexual impotence in male patients with chronic obstructive pulmonary disease and hypoxemia with long term oxygen therapy

Erectile impotence is commonly encountered in male patients with respiratory failure and hypoxia. In this study, 42% of the patients experienced reversal of sexual impotence during long-term oxygen therapy (LTOT). We examine the association between sexual impotence, gonadal axis hormones, hypoxia, and oxygen therapy. Nineteen sexually impotent male patients eligible for LTOT (pO2 < 7.3 kPa during stable disease) and with sexual impotence received oxygen therapy for 1 month (n = 12) or 24 h (n = 7). pO2, LH, FSH, testosterone, and SHBG (sex hormone binding globulin) were monitored. Five of 12 patients receiving oxygen for 1 month regained sexual potency. The responders showed a significant increase in arterial pO2 and serum testosterone, and a decline in SHBG compared to non-responders. None of the patients receiving oxygen for 24 h experienced reversal of sexual impotence, despite a significant increase in pO2. In these patients, serum testosterone did not increase significantly. Reversal of sexual impotence may be achieved in some patients with respiratory failure. The oxygen therapy must, however be administered for an adequate length of time.

Methotrexate measurements in plasma: comparison of enzyme multiplied immunoassay technique, TDx fluorescence polarization immunoassay, and high pressure liquid chromatography.

One hundred nine patient plasma samples were examined for methotrexate (MTX) levels by enzyme multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (TDx), and high pressure liquid chromatography (HPLC). EMIT analysis was performed twice within a time span of 18 months. All three methods measure MTX with a high degree of specificity, sensitivity, and precision. There was no evidence of decay of MTX concentrations in samples stored at -20 degrees C for 1.5 years. EMIT, TDx, and HPLC are adequate methods for MTX quantification in the clinical laboratory.

Radioprotection by murine and human tumor-necrosis factor: dose-dependent effects on hematopoiesis in the mouse.

Tumor‐necrosis factor (TNF) has been shown to confer significant radioprotection in murine models. Herein, we demonstrate a dose‐dependent enhancement of hematological recovery when single doses of either murine or human recombinant TNF are administered prior to irradiation. In addition to its action upon leukocytes and erythrocytes, TNF also alleviates radiation‐induced thrombocytopenia in the mouse. These effects on circulating blood constituents are further reflected in increased numbers of both primitive (CFU‐S) and more differentiated (CFU‐GM, CFU‐Mega) hematopoietic progenitors in TNF‐treated animals. This suggests that TNF exerts it radioprotective effects on a pool of primitive multi‐potential hematopoietic cells.

Tumor‐necrosis factor induces cell cycle arrest in multipotential hematopoietic stem cells: a possible radioprotective mechanism

Tumor‐necrosis factor (TNF) and interleukin‐1 (IL‐1) have been shown to confer protection of hematopoiesis in mice challenged with radiation. Herein, a series of experiments designed to elucidate the underlying mechanism is presented. After TNF administration, colony‐stimulating activity, but no IL‐1 activity, was detectable in mouse plasma. In endogenous CFU‐S assays, TNF enhanced the survival of multipotential progenitors when administered before, but not after, irradiation. In experiments with fractionated irradiation, the radioprotective effect of TNF was distinctly different from that of IL‐1. In vivo and in vitro thymidine suicide assays demonstrated that TNF wholly or partially abolished cell cycling of the CFU‐S hematopoietic compartment. These data imply that TNF may inhibit the cell cycle in hematopoietic progenitor cell populations.

Distribution of 7-hydroxymethotrexate in human blood

Abstract— We have examined the in‐vitro distribution of 7‐hydroxymethotrexate (7‐OH‐MTX), a cytotoxic metabolite of methotrexate (MTX), in human blood, and its protein binding in serum. The distribution of 7‐OH‐MTX (10−6 M) in fresh samples of whole blood was studied at 37 °C and pH 7.51 ± 0.05 (mean ± s.d.), and its protein binding was assessed by equilibrium dialysis of serum against Krebs Ringer phosphate buffer at 37 °C and pH 7.41 ± 0.07 (mean ± s.d.). 7‐OH‐MTX had a mean cell/plasma concentration ratio of 0.03 (range 0–0.27, n = 18). It was extensively bound in human serum, with a bound fraction of 90.4 ± 3.3% (mean ± s.d.) in healthy volunteers (n = 11), and significantly lower, 82.3 ± 4.0% (mean ± s.d.), in hypoalbuminaemic surgical patients (n = 7). The binding of 7‐OH‐MTX was correlated with serum albumin (HSA) concentrations (r = 0.72, P < 0.0007, n = 18). Blood distribution data support the contention that 7‐OH‐MTX has a small volume of distribution, and HSA appears to be mainly responsible for the high degree of its protein binding in serum.

Distribution of nortriptyline in human blood: effects of temperature, pH, and drug concentration

An in vitro study of putative factors causing postvenipuncture redistribution of the tricyclic antidepressant nortriptyline (NT) in blood was carried out in blood samples from a single subject. The influence of varying temperature, pH, and drug concentration on the protein binding of NT was assessed by equilibrium dialysis. The influence of the same variables on the distribution of NT in whole blood was measured by calculating the cell/plasma (C/P) drug concentration ratios after centrifugation of blood samples. Variation in temperature did influence the distribution of NT in blood considerably. From 4 to 37°C, the C/P ratio was found to increase from 1.0 ± 0.1 to 1.7 ± 0.2, and protein binding expressed as unbound fraction from 2.9 ± 0.2 to 7.1 ± 1.1% (mean ± SD). Neither pH variations within the 7.0–7.6 range, nor variations in drug concentration, were found to alter NT distribution at 37°C. The observed effect of temperature on NT distribution shows that handling of blood samples from patients taking NT should be standardized in order to avoid errors of interpretation.

Pituitary-Gonadal Dysfunction in Male Patients with Lung Cancer: Association with serum inhibin levels

Male lung cancer patients with poor performance status have an endocrinological dysfunction shown by decreased serum levels of total and free testosterone (AFTC). The intention was to investigate whether or not inhibin plays a role in gonadal dysfunction observed in male patients with malignant pulmonary disease. Twenty-seven patients with locally advanced non-small cell lung cancer were included. Sixteen patients were within ECOG index 1-2 (group A) and 11 patients within ECOG index 3-4 (group B). Gonadal function was monitored by serum LH, FSH, testosterone, SHBG and inhibin levels. Patients with poor performance status displayed significantly lower inhibin (1.6 +/- 0.8 U/I) and AFTC (0.23 +/- 0.07 nmol/l) levels when compared to patients within ECOG index 1-2 (inhibin 2.4 +/- 1.1 U/I; AFTC 0.66 +/- 0.36 nmol/l). Serum inhibin tended to correlate inversely to FSH with a 4.4-fold higher FSH/inhibin ratio in group B compared to A.