Morality in autism spectrum disorder: A systematic review.

Moral reasoning and decision making help guide behavior and facilitate interpersonal relationships. Accounts of morality that position commonsense psychology as the foundation of moral development, (i.e., rationalist theories) have dominated research in morality in autism spectrum disorder (ASD). Given the well-documented differences in commonsense psychology among autistic individuals, researchers have investigated whether the development and execution of moral judgement and reasoning differs in this population compared with neurotypical individuals. In light of the diverse findings of investigations of moral development and reasoning in ASD, a summation and critical evaluation of the literature could help make sense of what is known about this important social-cognitive skill in ASD. To that end, we conducted a systematic review of the literature investigating moral decision making among autistic children and adults. Our search identified 29 studies. In this review, we synthesize the research in the area and provide suggestions for future research. Such research could include the application of an alternative theoretical framework to studying morality in autism spectrum disorder that does not assume a deficits-based perspective.

A randomized double-blind comparison of diltiazem and nifedipine in stable angina.

A double-blind crossover trial comparing diltiazem (360 mg/day) and nifedipine (120 mg/day) for treatment of stable angina was conducted in 21 of 27 patients with proven coronary artery disease who completed the trial. All patients started with a 2 week placebo period followed by a random assignment to either drug treatment for 3 weeks and subsequent crossover to the other treatment. The two drug treatment periods were separated by a 1 week placebo washout phase and the study was completed with a 1 week placebo phase. There were no significant differences between patients' responses to diltiazem and nifedipine in relation to time to onset of angina, ST depression responses to exercise, heart rate or systolic or diastolic blood pressure. A total of 37 adverse effects were reported with nifedipine compared with 9 with diltiazem in the 22 patients in whom drug safety was analyzed. Additionally, two patients treated with nifedipine were withdrawn from study participation before crossover. There was a significant (p less than 0.05) difference with respect to incidence of edema (7 of 22 patients taking nifedipine, 1 of 22 taking diltiazem) and dizziness (7 of 22 patients taking nifedipine, 0 of 22 taking diltiazem). The most frequent adverse effect reported with diltiazem was rash (3 of 22 patients). Severe adverse effects were reported in four patients: in one with diltiazem (rash) and in three with nifedipine (palpitation in two and headache in one). A reduction in prescribed dosage was required in 37% of nifedipine-treated compared with 6% of diltiazem-treated patients. Efficacy measures were significantly improved above placebo levels by both diltiazem and nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of sustained-release diltiazem for stable angina pectoris.

Sustained-release diltiazem, 120 and 180 mg twice daily, was assessed in a multicenter, double-blind, randomized, placebo-controlled trial in 65 stable angina patients with exercise-induced ST depression. Exercise testing was performed 12 +/- 1 hours after the last dose at the end of each of the 3 treatment weeks. Both dose levels of drug reduced spontaneous angina (p less than 0.001) and increased exercise duration (p less than 0.01) and time to 1-mm ST depression (p less than 0.001). No differences were noted between the 2 dose levels. Rate-pressure product at maximal exercise was similar for the 3 groups. Only 1 patient terminated the study because of adverse drug effects; severe adverse effects occurred in 1 placebo and 1 low-dose period. Sustained-release diltiazem is safe and efficacious monotherapy for patients with stable angina.

Comparative efficacies of erythromycin-sulfisoxazole and cefaclor in acute otitis media: a double blind randomized trial.

A prospective double blind trial compared the fixed combination of erythromycin-sulfisoxazole (E/S) with cefaclor in the treatment of acute otitis media. One hundred nineteen children in six centers across Canada were studied. Diagnostic tympanocentesis of 134 ears yielded 135 bacterial isolates: Streptococcus pneumoniae (42%); Haemophilus influenzae (21%); Branhamella catarrhalis (10%); Streptococcus pyogenes (5%); and other bacteria (22%). Seventy-seven percent of strains of B. catarrhalis and 14% of strains of H. influenzae were beta-lactamase producers. E/S exhibited greater in vitro activity against H. influenzae and B. catarrhalis. Twenty-three patients had bacteriologically sterile middle ear fluid. The overall clinical outcome at Days 10 and 31 was identical in both treatment groups. Otoscopic findings improved more rapidly in the E/S group than in the cefaclor group at 10 and 31 days (P less than or equal to 0.04). In cases where pre-treatment middle ear fluid was negative on routine bacterial culture, complete cure at 10 days was observed in 75% of patients treated with E/S but only in 14% of those treated with cefaclor (P = 0.02). Side effects were infrequent and comparable between the test drugs. E/S is at least as effective as cefaclor in the management of acute otitis media and may be superior, particularly for cases not yielding bacteria on routine culture.

Early morphological abnormalities in splotch mouse embryos and predisposition to gene- and retinoic acid-induced neural tube defects.

Genetic and environmental factors contribute to an individual's neural tube defect liability. In the mouse, the gene mutation Splotch (Sp) causes a pigmentation defect in heterozygotes while homozygotes have spina bifida +/- exencephaly. Splotch homozygotes, heterozygotes, and wild-type embryos were examined for somite number, anterior neuropore closure, and posterior neuropore length. The aim was to distinguish potentially affected homozygotes early in pathogenesis and find a morphological basis for increased teratogen susceptibility in heterozygotes. Posterior neuropore closure as well as anterior neuropore closure was significantly delayed in potentially affected Sp as compared to wild-type litter embryos exceeding the incidence found in day-10-diagnosed homozygotes. Part of this excess was attributed to a transient delay in heterozygotes which in turn might predispose to retinoic acid-induced neural tube defects. This idea was supported by an outcross of Sp heterozygote males by inbred SWV females and wild-type males by SWV where a significant increase in retinoic acid-induced neural tube defects was found in Sp carrier litters.

Pharmacokinetics and safety of single intravenous and oral doses of dolasetron mesylate in healthy women.

Twenty-four healthy women received 2.4 mg kg-1 dolasetron mesylate (1.8 mg kg-1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0.08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0.08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2 = 0.23 h) to MDL 74156 (mean t1/2 = 8.05 and 9.12 h after intravenous and oral administration respectively). MDL 74156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non-significant changes in PR, QRS, and QTc intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men.