Studies on the abstinence-like overshoot following reversal of the potent 19-isoamyl derivative of etorphine with naloxone. A comparison with the opioids fentanyl and alfentanil.

Reversal of opioid-related respiratory depression is often accompanied by an "acute abstinence like syndrome" with hypertension, tachycardia, and pain. This overshoot was used to investigate the extent at which opioids of high potency but different structure are involved in naloxone-induced abstinence. In 10 awake and trained mongrel dogs two highly mu-selective compounds, alfentanil and fentanyl, were given in cumulative doses and at different occasions (30-60-120-240 micrograms/kg, and 6-12-24-48 micrograms/kg, respectively). Subsequently, a high dose of naloxone (100 micrograms/kg) was given at 5 min intervals while arterial blood gases, blood pressure, heart rate and the somatosensory evoked potential (SEP) were measured continuously. Following a wash-out period, the 19-isoamyl derivative of etorphine (M-140; 10,000 times more potent than normorphine and a 4.5 fold potency of ethylketocyclazocine in a bioessay preparation) was also given in increasing doses (0.2-0.4-0.8-3.2 micrograms/kg). Again, naloxone was given (100 micrograms/kg) at 5 min interval, while cardiovascular parameters, blood gases and SEPs were measured continuously. All three opioids induced a dose-related respiratory depression with hypercarbia and hypoxia, a dose-related bradycardia, and a modest hypotension. This was accompanied by a dose-related depression of the amplitude of the SEP, reflecting the degree of blockade of nociceptive afferents. Naloxone was sufficient to reverse respiratory impairment after fentanyl, alfentanil and M-140. However, in contrast to fentanyl and alfentanil, there was no cardiovascular or evoked potential overshoot following naloxone reversal of M-140. After alfentanil naloxone increased blood pressure, heart rate and amplitude of the SEP by 7%, 41% and 38%, respectively. After fentanyl this increase in blood pressure, heart rate and amplitude of the SEP was 17%, 43% and 96%, respectively. The study indicates that the more potent the opiate mu ligands are the more is naloxone liable to induce a hyperexcitatory state of the cardiovascular system and an increase of nociceptive stimuli to pain modulating centres. After M-140 reversal of mu-related respiratory depression by naloxone was possible. However, no precipitation on an acute abstinence-like syndrome affecting antinociception or inducing cardiovascular overshoot was observed. This may stem from an intense binding and slow dissociation of the ligand from the receptor site or may be due to high binding affinity to both the mu and the kappa receptor site. Opioids which interact with various receptor sites may be of clinical interest for substitution therapy in opioid dependent addicts.

Apparent size contrasts of retinal images and size constancy as determinants of the moon illusion.

Kaufman and Rock (1962) and Rock and Kaufman (1962) concluded that the moon illusion is a function of and attributable to apparent distance. They also reported a large framing effect as an exception. Analysis of the effect suggests two components which can account for the illusion independently of apparent distance. These are apparent size contrasts of visual images of discriminable features or objects of the earth with the moon's image and size constancy of the features or objects plus the interactions of the two. Apparent distances to horizons are always a consequence of the necessary conditions for the illusion. They are related to the illusion but are not a determinant of it.

Brunswik ratios: a ratio scale for comparative analyses of size constancy data from different experiments.

The literature on visual size constancy implicitly assumes that the perceived size of any dimension of a thing is evidence of how well (a) any other dimension of the thing will be perceived and (b) any visible dimension of any other thing will be perceived under comparable conditions of perception. For tests of these assumptions Brunswik ratios (1956) are described as a common conceptual and numerical basis, a ratio scale, for testing statistically for differences among or the equivalence of two or more sets of data from different experiments on visual size constancy.

Estrogen biosynthesis from testosterone-4-14C by post-ovulatory human ovaries. Comparison between the corpus-luteum ovary and its partner.

PIP: The whole of each ovary from 2 women in the luteal phase of normal cycles was incubated with testosterone-4-carbon-14 in order to test the postulate that an interaction between ovarian compartments might be involved in the post-ovulatory synthesis of estrogens. Estradiol, estriol and estrone were all identified, estriol in only one ovary, from the corpus-luteum ovary. In both women, the corpus-luteum ovary converted more than 60 times as much substrate to estrogens than its non-corpus-luteum partner, and produced markedly lower yields of testosterone, 4-androstene-3, 17-dione(androstene-dione) and of their 16-alpha-hydroxy derivatives. All 4 of these compounds were identified. The 19-hydroxy derivative of testosterone and androstene-dione were also identified, but with a less marked difference between the two ovaries. The markedly lower yields of the 16-alpha-hydroxy derivatives from the corpus-luteum ovaries indicates that they were being further metabolized. The yield of estriol was too low, however, to implicate this steroid as a final product of their conversion.^ieng

Urinary estrogens in spontaneous and induced ovulation in women.

PIP: Cycles of gonadotropin treatment were studied to gain information concerning the mechanisms involved in the postovulatory change in estriol (E3) production, particularly as regards the part played by progesterone, as it was previously postulated that progesterone was involved in this change. The subjects for the study were 4 young women who had regular 26-32 day cycles and 3 amenorrheic patients who were being treated with gonadotropins for long-standing infertility. Curves for total urinary estrogens (T.E.) in the 4 normal menstrual cycles studied and the assays for the proportion of the total accountable estriol (E3P) confirmed previous observations concerning the patterns for each consistently associated with spontaneous ovulation. In the similar studies during 5 cycles of gonadotropin therapy for the 3 amenorrheic patients, these same patterns were found in 3 cases (1 of which was the cycle of conception) but not in the other 2. Although all 5 of the treatment cycles showed evidence of progesterone secretion, these 2 failed to show the nadir in the T.E. curve or the increase in E3P characteristic of an ovulatory cycle. These observations have been confirmed by analysis of similar studies by others. They indicate that progesterone is not responsible for the postovulatory relative increase in E3, as had previously been proposed. They suggest, however, that such studies in gonadotropin-treated patients who secrete progesterone after treatment but fail to conceive, may be of assistance in differentiating ovulation from luteinization of unruptured follicles.^ieng