A new triphenylethylene compound,Fc-1157a

Summary The antitumor effects of a new antiestrogen, Fc-1157a¹ have been studied in vitro and in vivo. In vitro the effect of Fc-1157a was comparable to that of tamoxifen. The effect was dose-dependent, and at concentrations higher than 10^-6 mol/l Fc-1157a induced real cell death of the MCF-7 cells. In DMBA-induced mammary cancer in rats Fc-1157a decreased the number of new tumors and inhibited the growth of existing tumors, these effects being statistically highly significant. The ratio of growing tumors to stable and regressing tumors was significantly decreased. Although these effects were slightly stronger with Fc-1157a than with tamoxifen, the difference between these two compounds was not statistically significant.Murine uterine sarcoma, an estrogen receptor-negative tumor, was resistant to tamoxifen, but was statistically significantly inhibited by high doses (100 and 200 mg/kg^-1 day^-1 for 5 days) of Fc-1157a.The antitumor effects of Fc-1157a are due mainly to the antiestrogenic activity. At high concentrations in vitro and at high doses in vivo Fc-1157a exerts antitumor effects some of which are different from those of tamoxifen and are directed even against estrogen receptor-negative tumors. The exact mechanism of the observed cytolytic effect at high doses is unknown.     

Sympathetic auto-immune orchitis

Summary.  There is increasing evidence that, besides the immunization to sperm antigens and other immunological disorders, spontaneous auto-immune orchitis may also be an aetiological factor in male reproductive failure. The present paper describes a case study, where a surgical operation for an inguinal hernia caused an orchitis first in the ipsilateral, and few weeks later also in the contralateral testis and which finally led to an atrophy of both testicles. The time-course, patient's symptoms and especially the final histological picture all indicate that this process had an immunological basis, and therefore it is proposed that it should be called 'auto-immune sympathetic orchitis'.     

Changes in MMP‐2 and ‐9 Activity and MMP‐8 Reactivity After Amphotericin B Induced Synovitis and Treatment with Bufexamac

The objective here was to evaluate the acute effects of induced arthritis on synovial fluid (SF) levels of matrix metalloproteinases (MMP) ‐2, ‐8 and ‐9 in horses. To evaluate MMP‐2 and ‐9 activities and the effect of non‐steroidal anti‐inflammatory drug (NSAID) bufexamac during remission from acute arthritis. Aseptic arthritis was induced in 24 Standardbred horses using 20 mg of amphotericin B as a single intra‐articular (IA) injection in the right intercarpal joint. After 1 week and 2 weeks, horses were treated intra‐articularly with 10, 20, or 40 mg of bufexamac suspension or with sterile saline solution as control. SF was sampled prior to induction and at weekly intervals for 5 weeks. Fluids were evaluated for MMP‐2 and MMP‐9 activity by gelatin zymography or for MMP‐8 immunoreactivity by Western Blotting. IA injection of amphotericin B consistently resulted in significant increase in the immunoreactivity of MMP‐8 and activity of both the latent and the active forms of MMP‐2 and ‐9, among which the active form of MMP‐2 increased the most. MMP‐9 levels declined to pre‐induction levels within 2 weeks, whereas levels of MMP‐2 remained still high after 5 weeks. Treatment with bufexamac did not significantly affect levels of gelatinolytic MMP. Results suggest that after acute arthritis of horses, elevated MMP activity is present in the joint, for several weeks, to a degree that could promote cartilage degradation, and treatment with the NSAID bufexamac is not likely to affect that. Furthermore, analysing levels of MMP‐9 activity and especially levels of active forms of MMP‐2 activity may be valuable to predict the time of occurrence of arthritis in horses.     

The effect of temperature correction of blood gas values on the accuracy of end-tidal carbon dioxide monitoring in children after cardiac surgery

We evaluated accuracy of end-tidal carbon dioxide tension (PETco2) monitoring and measured the effect of temperature correction of blood gas values in children after cardiac surgery. Data from 49 consecutive mechanically ventilated children after cardiac surgery in the cardiac intensive care unit were prospectively collected. One patient was excluded from the study. Four arterial-end-tidal CO2 pairs in each patient were obtained. Both the arterial carbon dioxide tension (Paco2) values determined at a temperature of 37 degrees C and values corrected to body temperature (Patcco2) were compared with the PETco2 values. After the surgical correction 28 patients had biventricular, acyanotic (mean age 2.7 +/- 4.8 years) and 20 patients had a cyanotic lesion (mean age 1.0 +/- 1.7 years). The body temperature ranged from 35.2 degrees C to 38.9 degrees C. The Pa-PETco2 discrepancy was affected both by the type of cardiac lesion and by the temperature correction of Paco2 values. Correlation slopes of the Pa-PETco2 and Patc-PETco2 discrepancies were significantly different (p = 0.040) when the body temperature was higher or lower than 37 degrees C. In children, after cardiac surgery, end-tidal CO2 monitoring provided a clinically acceptable estimate of arterial CO2 value, which remained stabile in repeated measurements. End-tidal CO2 monitoring more accurately reflects temperature-corrected blood gas values.     

Toxicokinetics of methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) in humans, and implications to their biological monitoring

Healthy male volunteers were exposed via inhalation to gasoline oxygenates methyl tert-butyl ether (MTBE) or tert-amyl methyl ether (TAME). The 4-hr exposures were carried out in a dynamic chamber at 25 and 75 ppm for MTBE and at 15 and 50 ppm for TAME. The overall mean pulmonary retention of MTBE was 43 +/- 2.6%; the corresponding mean for TAME was 51 +/- 3.9%. Approximately 52% of the absorbed dose of MTBE was exhaled within 44 hr following the exposure; for TAME, the corresponding figure was 30%. MTBE and TAME in blood and exhaled air reached their highest concentrations at the end of exposure, whereas the concentrations of the metabolites tert-butanol (TBA) and tert-amyl alcohol (TAA) concentrations were highest 0.5-1 hr after the exposure and then declined slowly. Two consecutive half-times were observed for the disappearance of MTBE and TAME from blood and exhaled air. The half-times for MTBE in blood were about 1.7 and 3.8 hr and those for TAME 1.2 and 4.9 hr. For TAA, a single half-time of about 6 hr best described the disappearance from blood and exhaled air; for TBA, the disappearance was slow and seemed to follow zero-order kinetics for 24 hr. In urine, maximal concentrations of MTBE and TAME were observed toward the end of exposure or slightly (< or = 1 hr) after the exposure and showed half-times of about 4 hr and 8 hr, respectively. Urinary concentrations of TAA followed first-order kinetics with a half-time of about 8 hr, whereas the disappearance of TBA was slower and showed zero-order kinetics at concentrations above approx. 10 micro mol/L. Approximately 0.2% of the inhaled dose of MTBE and 0.1% of the dose of TAME was excreted unchanged in urine, whereas the urinary excretion of free TBA and TAA was 1.2% and 0.3% within 48 hr. The blood/air and oil/blood partition coefficients, determined in vitro, were 20 and 14 for MTBE and 20 and 37 for TAME. By intrapolation from the two experimental exposure concentrations, biomonitoring action limits corresponding to an 8-hr time-weighted average (TWA) exposure of 50 ppm was estimated to be 20 micro mol/L for post-shift urinary MTBE, 1 mu mol/L for exhaled air MTBE in a post-shift sample, and 30 micro mol/L for urinary TBA in a next-morning specimen. For TAME and TAA, concentrations corresponding to an 8-hr TWA exposure at 20 ppm were estimated to be 6 micro mol/L (TAME in post-shift urine), 0.2 micro mol/L (TAME in post-shift exhaled air), and 3 micro mol/L (TAA in next morning urine).     

Behavior of C-reactive protein in association with surgery of facial fracture and the influence of dexamethasone

Purpose

To clarify pre- and postoperative C-reactive protein (CRP) levels in patients with facial fractures and to investigate the influence of perioperatively administered dexamethasone on postoperative CRP levels.

Patients and methods

Facial fracture patients were randomized to receive perioperatively a total dose of 30 mg of dexamethasone (Oradexon®), whereas patients in the control group received no glucocorticoid. The analysis included patients who had CRP measured pre- and postoperatively.

Results

A total of 73 adult patients with facial fractures were included in the final analysis. Mean CRP level was elevated preoperatively and the level increased further after surgery. However, postoperative CRP rise was significantly impeded by dexamethasone (p?<?0.001), regardless of gender, age, treatment delay, site of fracture, surgical approach, and duration of surgery. CRP rise halved on the 1st postoperative day when dexamethasone was used. In addition, dexamethasone resulted in a CRP decrease on the 2nd postoperative day, whereas the CRP rise continued in the control group.

Conclusions

CRP rise is a normal body response after facial fracture and surgery that can be markedly reduced with dexamethasone. CRP changes should be considered with caution if perioperative dexamethasone is used.