Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients.

PURPOSE: To examine the consequences of administration of norepinephrine on muscle tissue oxygenation in severely hypotensive septic shock patients. METHODS: This was a prospective observational study conducted in a medical intensive care unit of a university hospital. We included 28 septic shock patients that received early volume resuscitation. All were eligible for receiving norepinephrine because of life-threatening hypotension and low diastolic arterial pressure. Muscle tissue oxygen saturation (StO2) and its changes during a vascular occlusion test were measured at the level of the thenar eminence using a near-infrared spectroscopy (NIRS) device. Transpulmonary thermodilution cardiac index (CI) and NIRS-derived variables were obtained before and after the mean arterial pressure (MAP) was increased by norepinephrine. The baseline StO2 and the vascular occlusion test-derived variables of 17 healthy volunteers were measured and served as controls. RESULTS: In healthy volunteers, StO2 ranged between 75 and 90% and StO2 recovery slopes ranged between 1.5 and 3.4%/s. Administration of norepinephrine, which was associated with an increase in MAP from 54 ± 8 to 77 ± 9 mmHg (p < 0.05), also induced increases in CI from 3.14 ± 1.03 to 3.61 ± 1.28 L/min/m² (p < 0.05), in StO2 from 75 ± 9 to 78 ± 9% (p < 0.05) and in StO2 recovery slope from 1.0 ± 0.6 to 1.5 ± 0.7%/s (p < 0.05). CONCLUSIONS: Norepinephrine administration aimed at achieving a MAP higher than 65 mmHg in septic shock patients with life-threatening hypotension resulted in improvement of NIRS variables measured at the level of the thenar eminence.

17alpha-ethyl-5beta-estrane-3alpha, 17beta-diol, a biological marker for the abuse of norethandrolone and ethylestrenol in slaughter cattle.

The metabolism of the illegal growth promoter ethylestrenol (EES) was evaluated in bovine liver cells and subcellular fractions of bovine liver preparations. Incubations with bovine microsomal preparations revealed that EES is extensively biotransformed into norethandrolone (NE), another illegal growth promoter. Furthermore, incubations of monolayer cultures of hepatocytes with NE indicated that NE itself is rapidly reduced to 17alpha-ethyl-5beta-estrane-3alpha, 17beta-diol (EED). In vivo tests confirmed that, after administration of either EES or NE, EED is excreted as a major metabolite. Therefore, it was concluded that, both in urine and faeces samples, EED can be used as a biological marker for the illegal use of EES and/or NE. Moreover, by monitoring EED in urine or faeces samples, the detection period after NE administration is significantly prolonged. These findings were further confirmed by three cases of norethandrolone abuse in a routine screening program for forbidden growth promoters.

Exposure to anabolic-androgenic steroids shortens life span of male mice.

Adult male laboratory mice were exposed for 6 months to a combination of four anabolic-androgenic steroids of the kinds and at the relative levels to which human athletes and body builders expose themselves. The four steroids included testosterone, two 17-alkylated steroids, and an ester, and they were given at doses that totaled either 5 or 20 times normal androgenic maintenance levels for mice. By the time the survivors were 20 months old (1 yr after the termination of steroid exposure), 52% of the mice given the high dose of steroids had died compared with 35% of the mice given the low dose and only 12% of the control mice given no exogenous hormones (P < 0.001). Autopsy of the steroid-treated mice typically revealed tumors in the liver or kidney, other kinds of damage to these two organs, broadly invase lymphosarcomas, or heart damage, and usually more than one of these conditions. It can be concluded that the life span of male mice is decreased dramatically by exposing them for 6 months to the kinds and relative levels of anabolic steroids used by many athletes and body builders.

[Effects of weakly androgenic anabolic steroids on growth in Turner's syndrome]. / Effets des stéroïdes anabolisants faiblement androgéniques sur la croissance dans le syndrome de Turner.

The effects of weakly androgenic steroids at minimal doses (norethandrolone 2.5 to 10 mg/day or methandienone 1 mg/day, administered 2 months every trimester) have been studied in 67 patients with Turner syndrome: 37 with 45 XO karyotype and 30 with mosaicism or partial X deletion. Mean bone age at the onset of treatment was 10 4/12 +/- 1 8/12 years, and the mean height retardation, adjusted to parents' height, was 3.7 +/- 1.2 standard deviations. Growth velocity was very significantly increased during the first 3 semesters of treatment. The ratio of bone age to height age, evaluated after 2 years of treatment, did not increase. The adult height reached by 37 treated patients was at the average 1.96 cm higher than that of a control group of 25 adult untreated Turner cases, this difference being not significant. The results varied greatly between individuals, without relation to the type of chromosomal abnormality or the kind and dose of steroid received. The psychological evolution of the treated patients was studied accordingly to their school and/or professional accomplishments. It was satisfactory in most of them. The anabolic treatment and/or the gain in growth velocity during treatment seemed to have positive psychological effect. No side-effects were noticed.

Evidence for microfilament involvement in norethandrolone-induced intrahepatic cholestasis.

An experimental study of norethandrolone (NED)-induced intrahepatic cholestasis was made. NED was infused via a portal vein catheter into rat liver in vivo, and measurements were made of bile flow. Liver specimens were taken at intervals for light microscopy and for transmission and scanning electron microscopy. Bile-canalicular-rich membrane fractions were prepared. The effects of NED were also examined in isolated hepatocytes in suspension culture. NED infusion induced total cholestasis by 3 hours. Canalicular alterations commonly associated with cholestasis were found in in vivo infused liver and in isolated hepatocytes. Pericanalicular microfilament changes were also noted in both, with loss of filament structure and replacement by a granular zone. In isolated canalicular membrane fractions prepared from NED-treated animals, the normal investment of pericanalicular filaments was no longer present. Loss of the bile canalicular ruthenium red surface coat was also noted. In view of the identical findings in isolated hepatocytes and in in vivo liver, obstruction and mechanical factors can be excluded as possible causes. The results raise the possibility that the mechanism of NED-induced cholestasis may be related to disaggregation and/or detachment of microfilaments from the canalicular membranes.