TRANSPLANTATION ANTIGENS AND KERATOPLASTY

Allograft rejection is one of the leading causes of corneal graft failure in man when the cornea is heavily vascularised. This paper reports the feasibility and possible benefits of using histocompatibility (HLA) antigen crossmatch testing and HLA-D locus antigen matching for corneal donor selection. Double-masked clinical trials designed to determine the value of these procedures for keratoplasty are discussed.     

Septo‐optic dysplasia in childhood: the neurological,cognitive and neuro‐ophthalmological perspective

Aim We set out to describe 17 patients with septo‐optic dysplasia (SOD), focusing on the little‐explored neurological, cognitive, and neuro‐ophthalmological components. A further aim was to identify possible clinical correlations and phenotypic characteristics within the diagnostic spectrum. Method We collected clinical‐instrumental data (from the history, general and neurological examination, developmental assessment, and neuro‐ophthalmological, neuroradiological, neurophysiological, and endocrinological evaluations) on nine males and eight females (mean age 34.4mo, SD 31.6; range 4mo‐9y 6mo) diagnosed with SOD who were referred to our Centre of Child Neuro‐ophthalmology between 1999 and 2010. Results We observed a heterogeneous clinical spectrum characterized by nervous system, visual, and endocrine dysfunctions; optic nerve involvement was present in all 17 children, midline brain defects in 14, and cortical developmental malformations in seven. Developmental/cognitive delay and relational and communication difficulties were observed in eight and seven children, respectively, and reduced visual acuity and oculomotor dysfunction were observed in all. Pituitary hormone deficiencies were present in nine children. Interpretation Nervous system involvement emerged as a key feature of SOD. As part of a holistic approach to the disease, particular attention should be paid to this aspect. The emergence of new clinical correlations and correlations between clinical features and three SOD subtypes opens the way for better clarification of this disease and, therefore, more targeted diagnosis, follow‐up, and care of affected children.     

Determinants of subjective experience of sexual arousal in women: Feedback from genital arousal and erotic stimulus content

Sixty-two women participated in a study designed to explore the association between gential and subjective sexual arousal. Four stimulus conditions were created, designed to evoke differential patterns of genital arousal over time. Subjects were instructed to report sensations in their genitalia while being exposed to the same erotic stimulus on repeated trials or to a series of varying erotic stimuli. Detection of genital arousal was facilitated by the occurrence of changes in genital arousal over trials. That is, genital and subjective sexual arousal were linearly related in conditions that resulted in large differences in genital arousal over trails, whereas such a relation was absent in conditions in which genital arousal levels remained relatively constant. In women, peripheral feedback from consciously detected genital arousal seems to be a relatively unimportant determinant of subjective sexual arousal.     

ANTINOCICEPTIVE EFFECTS OF THE HYDROPHILIC α2-ADRENOCEPTOR AGONIST ST-91 IN DIFFERENT TEST CIRCUMSTANCES AFTER INTRATHECAL ADMINISTRATION TO WISTAR RATS

The antinociceptive and motor effects of the hydrophilic α₂-adrenoceptor agonist ST-91 were studied after intrathecal administration to male Wistar rats in different heat–pain tests and different test settings. Intrathecal administration of ST-91 caused a dose-dependent increase in hind paw licking latency in the hot-plate test, while in contrast with morphine it had a much lower efficacy in the tail-flick test in freely moving conditions. Sprague–Dawley rats gave similar results to those for Wistar rats in this setting. However, when the tail-flick test was performed under chronic restraint conditions (after a 1-h restraining period), the compound caused a significant antinociception. No signs of motor impairment and no changes in electromyographic activity were detected after ST-91 administration. The results indicate a characteristic analgesic profile for ST-91. In the interpretation of ST-91 data, consideration should be paid both to test model differences and to test conditions.     

4,4'-Methylene-bis(2-chloroaniline) (MOCA): Comparison of Macromolecular Adduct Formation after Oral or Dermal Administration in the Rat

4,4'-Methylene-bis(2-chloroaniline) (MOCA): Comparison of MacromolecularAdduct Formation after Oral or Dermal Administration in theRat. CHEEVER, K. L., RICHARDS, D. E., WEIGEL, W. W., BEGLEY,K. B., DEBORD, D. G., SWEARENGIN, T. F., AND SAVAGE, R. E. JR.(1990). Fundam. Appl. Toxicol. 14, 273–283. The macromolecularbinding of 4,4'-methylene-bis(2-chloroaniline) (MOCA), a suspecthuman carcinogen, was studied in the adult male Sprague-Dawleyrat after both oral and dermal administration. Rats were euthanized1, 3, 7, 10, 14, and 29 days after a single 281 µmol/kgbody wt dose of [¹⁴C]MOCA (oral, 213 µCi/kg; dermal, 904µCi/kg). DNA from various tissues and hemoglobin wereisolated for determination of the time course of MOCA macromolecularbinding. After oral administration adduct formation was rapidwith maximum levels appearing at 24 hr. The 24-hr covalent bindingassociated with the globin was 7.84 pmol/mgglobin (t? = 14.3days). More extensive 24-hr covalent binding was detected forliver DNA with 49.11 pmol/mg DNA (t? = 11.1 days). After dermaladministration of MOCA the major portion of the dose, 86.2%,remained at the application site throughout the study. For theserats the 24-hr covalent binding determined for liver DNA was0.38 pmol/mg DNA (t? = 15.6 days). Although lower levels weredetected after dermal application, similar stability of MOCA-DNAadducts indicates that quantification of such MOCA adducls maybe useful for the long-term industrial biomonitoring of MOCAexposure and for the evaluation of human DNA-MOCA adduct formation,a lesion thought to be associated with the production of cancer.     

Preclinical Toxicology Studies with Acyclovir: Teratologic, Reproductive and Neonatal Tests

Preclinical Toxicology Studies with Acyclovin Teratologic, Reproductiveand Neonatal Tests. Moore, H.L., Jr., Szczech, G.M., Rodwell,D.E., Kapp, R.W., Jr., de Miranda, P. and Tucker, W.E., Jr.(1983).Fundam. Appl Toxicol 3:560–568. Five studies weredone to define the potential of Acyclovir (ACV), a new nucleosideanalog for antiviral chemotherapy, to produce adverse effectson reproduction and development in laboratory animals. ACV producedno adverse effects when given by gavage to F₀ generation miceat 50, 150 and 450 mg/kg/day in a two generation reproduction/fertilitystudy. Some mice were evaluated for teratologic effects andothers for postnatal development, including behavior, with negativeresults. ACV was not embryotoxic and did not increase the incidenceof fetal malformations when given by subcutaneous injectionto pregnant rats and rabbits at dose levels of 12, 25 and 50mg/kg/day during the periods of major organogenesis. A comparativeLD₅₀ study revealed that 3-day-old rats were not more sensitiveto acute toxic effects of ACV than more mature rats. Finally,in a comprehensive multidose toxicity study ACV was given subcutaneouslyto neonatal rats at 5, 20 and 80 mg/kg/day for 19 consecutivedays. There was minimal effect on body weight gain in neonatestreated at 20 mg/kg/day and a significant decrease in body weightgain at 80 mg/kg/day. Minimal renal lesions occurred at 80 mg/kg/ day but no other signs of adverse effects on developingorgan systems were observed. Except for decreased body weightgain in neonatal rats treated at 80 mg/kg/day, ACV did not produceadverse effects on mammalian development when tested in a varietyof preclinical toxicology studies.