Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.     

Benign neonatal sleep myoclonus: case report and follow-up of four members of an affected family.

Benign neonatal sleep myoclonus (BNSM), characterized by myoclonic jerks of the extremities only in non-REM sleep, occurs in the first months of life with spontaneous disappearance within 3-4 months. We examined five siblings with typical BNSM, at the 3-10 years follow-up neurological examination. Psychomotor development, cognitive functions and EEG were completely normal. These cases confirm that BNSM is a self limited and nonepileptic disorder.     

Hormonal and immunological pattern in a patient with acquired immunodeficiency syndrome related complex and Cushing's syndrome.

A case of Cushing's syndrome in a 24-yr-old homosexual with an AIDS-related complex is reported. In this patient certain symptoms common to both diseases, i.e. weakness, myalgia and muscle atrophy were accentuated, whereas other symptoms pathognomic of the human immunodeficiency virus (HIV) infection, i.e. lymphoadenopathies and weight loss, were less pronounced by the high levels of circulating adrenal steroids. Ketoconazole was administered po in order to block adrenal steroidogenesis, the drug caused a remarkable fall of cortisol serum concentrations, but was unable to modify significantly the immunological pattern of the patient. Our data suggest that changes of serum adrenal steroid levels have little effect on the immune network of patients with AIDS.     

Interleukin-1 beta and beta-endorphin circadian rhythms are inversely related in normal and stress-altered sleep.

Normal sleep is associated to physiological nocturnal rises in Interleukin 1 beta (IL 1 beta) secretion. The 24 h pattern of IL 1 beta, beta-Endorphin (beta-EPH), ACTH and cortisol (F) production was evaluated in four male healthy volunteers. Two subjects were unable to sleep, due to the stress of the experiment; in these cases, no detectable plasma IL 1 beta secretion, both diurnal and nocturnal, was present, beta-EPH plasma levels were significantly higher (p < 0.01) than in the subjects who slept regularly and, in one case, increased F plasma levels were also reported. A strong negative correlation between IL 1 beta and beta-EPH plasma levels was present in all the cases. In conclusion, stress-induced sleep alterations might deeply affect both diurnal and nocturnal IL 1 beta plasma secretion, probably due to the hypothalamus-pituitary-adrenal axis (HPAA) activation, and beta-EPH might be the reliable marker of the stress-induced HPAA activation level.     

The effect of first metatarsophalangeal joint arthrodesis on the first ray and the medial longitudinal arch: a radiographic study.

The purpose of this study was to examine the effect of first metatarsophalangeal arthrodesis on the sagittal plane orientation of the first ray and the medial longitudinal arch. Lateral weightbearing radiographs of 48 patients (54 feet) having undergone the procedure were retrospectively reviewed. Patients were separated into three groups based on their preoperative diagnosis: hallux rigidus, hallux valgus, or rheumatoid forefoot deformity. First metatarsal declination, talometatarsal, talar declination, calcaneal inclination, and talocalcaneal angles were measured on pre- and postoperative radiographs. Multivariate analysis of variance determined that there was a significant postoperative change (p < .001) in angular measurements, particularly in the first metatarsal declination, talometatarsal, and talocalcaneal angles. There was also a significant difference (p < .01) in the angular measurements between the hallux rigidus group and the other two groups. However, the amount of change from pre- to postoperatively did not vary significantly between the groups. A calculation of Pearson correlation coefficients found no significant correlation between the hallux dorsiflexion angle and changes in angular measurements. The radiographic changes found in this study support Hicks' windlass model: fixed dorsiflexion of the hallux causes plantarflexion of the first ray and an increase in the medial longitudinal arch.     

Non-invasive evaluation with continuous Doppler of the systolic pressure of the right ventricle in patients with tricuspid insufficiency

Tricuspid regurgitation (TR) is detected by Doppler echocardiography in a high proportion of patients with right ventricle pressure or volume overload. Continuous wave Doppler (CW) provides a noninvasive estimation of the transtricuspid systolic pressure gradient, applying the modified Bernoulli formula to the maximum velocity of the TR jet. The purpose of this study was to test the accuracy of the CW prediction of systolic right ventricular pressure (RVPs), obtained adding a clinical estimate of the mean right atrial pressure (RAPm) to the Doppler derived pressure gradient. The study population consisted of 22 adult patients with Doppler proved TR, undergoing right heart catheterization (cath) for mitral valve disease (12 pts), atrial septal defect (8 pts), dilated cardiomyopathy (1 pt) or pulmonary hypertension (1 pt). Two studies were duplicated after nifedipine administration. TR was graded by pulsed Doppler flow mapping as mild in 7, moderate in 11, severe in 4 pts. RAPm was estimated clinically from the inspection of neck veins pulsatility (mmHg = pulsatility cm+5/1.3). At CATH RVPs ranged from 27 to 80 (46 +/- 17) mmHg, RAPm from 0 to 13 (6 +/- 3) mmHg. RVPs Doppler prediction showed a close correlation with CATH (r .97, SEE 4.2 mmHg), with a slight mean underestimation (-2 +/- 4 mmHg) (Fig. 3, Tab. I). The discrepancies between CW and CATH ranged from -9 to +10 mmHg, almost entirely due to inaccuracy of the RAPm clinical estimate (r .48, see 3.8 mmHg) (Fig. 4, Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS)