Safety profile of intravenous and subcutaneous siplizumab,an anti‐CD2 monoclonal antibody,for the treatment of plaque psoriasis: results of two randomized,double‐blind,placebo‐controlled studies

Several biologics targeting different cytokines and receptors, including T‐cell receptors, have been approved for psoriasis treatment. Siplizumab, a humanized anti‐CD2 monoclonal antibody, may potentially provide an alternative therapy for psoriasis. Its safety profile and immunogenicity was examined in adults with plaque psoriasis. Two multicenter phase II randomized, double‐blind, placebo‐controlled studies: one tested two intravenous (I.V.) doses (0.012 and 0.04 mg/kg) of siplizumab every 2 weeks × 8 doses (124 patients); the second study tested three subcutaneous (S.C.) dose regimens of siplizumab (5 mg × 12 weeks, 5 mg × 6 weeks + placebo × 6 weeks, 7 mg × 4 weeks + placebo × 8 weeks), and placebo × 12 weeks (420 patients). Adverse events (AEs) and laboratory values were monitored. Immunogenicity was determined by anti‐siplizumab antibodies quantification. In both studies, siplizumab exhibited an acceptable safety profile; most common AEs judged to be siplizumab related were lymphopenia, chills, and headache, reported at a higher frequency in the siplizumab‐treated vs. placebo group. Siplizumab‐related reductions in absolute lymphocyte count did not result in clinical evidence of immune suppression. Anti‐siplizumab antibodies were detected after exposure to siplizumab; however, there was no evidence of an association between antibody development and AEs. Siplizumab exhibited an acceptable safety profile in adult patients with plaque psoriasis when administered as multiple I.V. or S.C. doses. Higher, clinically relevant doses of siplizumab would need to be tested to fully assess its safety.     

Scales for the measurement of attitudes toward blood donation

Attitudes toward blood donation are frequently assumed to vary along a single dimension from unfavorable to favorable. In contrast, theories of attitude structure specify three distinct attitude components: affect, cognition, and behavior. This article describes the development of three new scales for the measurement of affective, cognitive, and behavioral components of attitudes toward blood donation. The scales were developed using the method of equal-appearing intervals and were administered to both donors of blood and nondonors. Correlations among the scales were relatively small and supported the three-component distinction. Affect was more strongly correlated with the number of prior donations than was cognition, which suggested an important role for emotional factors in blood donation. Scores on all three scales showed the attitudes of blood donors to be more favorable than those of nondonors.     

The influence of bright light during the daytime upon circadian rhythm of core temperature and its implications for nocturnal sleep

Abstract The purpose of the present study was to investigate how bright light during the daytime could influence circadian rhythms of core temperature and nocturnal sleep. Seven females (age 20 ± 2 years) served as participants. The participants lived in the experimental unit for 4 days and were exposed to either 6000 lx (bright) or 200 lx (dim) light during the daytime. Rectal temperature (T_re) was measured during the experimental period. Subjective alertness was measured by the Kansei-gakuin Sleeping Scale five times a day. The minimum T_re was significantly lower after bright exposure ( P < 0.05). The T_re fell rapidly after bright exposure before they retired ( P < 0.05) and increased more rapidly during bright light after they woke up ( P < 0.05). The morning wakefulness under bright exposure was more active than under dim exposure ( P < 0.05). The melatonin secretion at wake up during bright exposure was significantly lower than during dim exposure ( P < 0.05). Exposure to bright light during daytime lowered the nocturnal level of T_re, its evening fall was faster and the morning rise quicker. This suggests that indoor light during daytime should be bright enough to promote healthy sleep at night.     

Rejection sensitivity and multiple group memberships: The moderating role of an oxytocin receptor gene polymorphism

Rejection sensitivity is a cognitive-affective processing disposition that has been linked to interpersonal difficulties. In this regard, the neuropeptide hormone, oxytocin, is thought to underlie social cognitions and behaviors that promote social affiliation. A single nucleotide polymorphism (SNP) on the oxytocin receptor gene (OXTR), in which guanine (G) is substituted for adenine (A), has been associated with less support-seeking behaviors. In the current study, among 376 undergraduate students, it was shown that the relationship between rejection sensitivity and depressive symptoms was mediated by multiple group memberships. Furthermore, the relation between rejection sensitivity and group memberships was only evident among individuals possessing the A allele on the OXTR gene. These findings further support the psychosocial deficits characteristic of individuals possessing the OXTR polymorphism, which in turn is linked to poor mood.     

Persistence of acanthamoeba antigen following acanthamoeba keratitis

AIM: To investigate the hypothesis that persistent corneal and scleral inflammation following acanthamoeba keratitis is not always caused by active amoebic infection but can be due to persisting acanthamoebic antigens METHODS: 24 lamellar corneal biopsy and penetrating keratoplasty specimens were obtained from 14 consecutive patients at various stages of their disease and divided for microscopy and culture. Histological sections were immunostained and screened for the presence of Acanthamoeba cysts by light microscopy. Cultures were carried out using partly homogenised tissues on non-nutrient agar seeded with E coli. Clinical data were obtained retrospectively from the case notes of these patients. RESULTS: Of the 24 specimens, 20 were obtained from eyes that were clinically inflamed at the time of surgery. Acanthamoeba cysts were present in 16 (80%) of these 20 specimens, while only five (25%) were culture positive. Acanthamoeba cysts were found to persist for up to 31 months after antiamoebic treatment. CONCLUSION: These findings support the hypothesis that Acanthamoeba cysts can remain in corneal tissue for an extended period of time following acanthamoeba keratitis and may cause persistent corneal and scleral inflammation in the absence of active amoebic infection. In view of these findings, prolonged intensive antiamoebic therapy may be inappropriate when the inflammation is due to retained antigen rather than to viable organisms