R-(-)-ketamine modifies behavioral effects of morphine predicting efficacy as a novel therapy for opioid use disorder1.

Substance abuse disorder continues to have devastating consequences for individuals and society and current therapies are not sufficient to provide the magnitude of medical impact required. Although some evidence suggests the use of ketamine in treating various substance use related- symptoms, its adverse event profile including dissociation, dysphoria, and abuse liability limit its potential as a therapy. Here, we outline experiments to test our hypothesis that (R)-ketamine can both alleviate withdrawal symptoms and produce effects that help sustain abstinence. In morphine-dependent rats, (R)-ketamine alleviated naloxone-precipitated withdrawal signs. (R)-ketamine also blocked morphine-induced place preference in mice without inducing place preference on its own. We also evaluated whether (R)-ketamine would induce anhedonia, a counter-indicated effect for a drug abuse treatment agent. S-(+)- but not R-(-)-ketamine produced anhedonia-like responses in rats that electrically self-stimulated the medial forebrain bundle (ICSS). However, time-course studies of ICSS are needed to fully appreciate these differences. These data begin to support the claim that (R)-ketamine will dampen withdrawal symptoms and drug liking, factors known to contribute to the cycle of drug addiction. In addition, these data suggest that (R)-ketamine would not produce negative mood or anhedonia that could interfere with treatment. It is suggested that continued investigation of (R)-ketamine as a novel therapeutic for substance abuse disorder be given consideration by the preclinical and clinical research communities. This suggestion is further encouraged by a recent report on the efficacy of (R)-ketamine in treatment-resistant depressed patients at a dose with little measurable dissociative side-effects.

Anatomical risk factors for phonological dyslexia.

Successful behavioral genetic studies require precise definition of a homogenous phenotype. This study searched for anatomical markers that might restrict variability in the reading disability phenotype. The subjects were 15 college students (8 male/7 female) diagnosed with a reading disability (RD) and 15 controls (8 males/7 females). All subjects completed a cognitive and reading battery. Only 11 of the RD subjects had a phonological deficit [phonological dyslexia (PD): pseudo word decoding scores < 90 (27th percentile)]. Thirteen RD (9 PD) and 15 controls received a volumetric MRI scan. Four anatomical measures differentiated the PD group from the remainder of the subjects: (i) marked rightward cerebral asymmetry, (ii) marked leftward asymmetry of the anterior lobe of the cerebellum, (ii) combined leftward asymmetry of the planum and posterior ascending ramus of the sylvian fissure, and (iv) a large duplication of Heschl's gyrus on the left. When these four measures were normalized and summed, the resulting variable predicted short- and long-term phonological memory. By contrast, oral and written comprehension skills were predicted by a different anatomical variable: low cerebral volume. These findings provide neurobiological support for an RD phenotype characterized by phonological deficits in the presence of normal or superior comprehension. The study of individual variation in cortical structure may provide a useful link between genotype and behavior.

An initial investigation of validation of the Matrix Analogies Test-Expanded Form in Ecuador.

This is a first preliminary study of the validity and reliability of the Matrix Analogies Test--Expanded Form in South America. Participants were 104 Spanish-speaking children between the ages of 5 and 17 years living in Ecuador. Values of Cronbach alpha ranged from .87 to .92 for the 4 groups of items and was .95 for the total score. Raw scores on the MAT increased across ages. Scores of boys did not differ significantly from those of girls. Total test scores correlated significantly with scores on the Raven Standard Progressive Matrices (r = .62, p < .005; r = .82 before controlling for age). A principal factor analysis conducted to provide evidence of the test's construct validity indicated that all four sets of items loaded substantially on one unrotated factor, presumed to be g. In sum, these results suggest that the test is a valid and reliable nonverbal measure of general cognitive ability in this population.

Is short stature a handicap? A comparison of the psychosocial functioning of referred and nonreferred children with normal short stature and children with normal stature.

OBJECTIVES: Normal short stature (NSS), defined as height below the 5th percentile for age and sex norms that is not due to illness, hormonal deficiency, or part of a dysmorphic syndrome, has been thought to have a deleterious effect on psychosocial functioning based on observations of referred populations. Recent studies of nonreferred children with NSS, however, have demonstrated normal function. This study directly compared the psychosocial functioning of referred children with NSS, nonreferred children with NSS, and children with normal stature. STUDY DESIGN: Participants, 90 children (46 boys, 44 girls) between 6 and 12 years of age (mean, 9. 6 years), were administered intelligence and achievement tests. Parents and teachers assessed adaptive and problem behaviors. Family adaptability and cohesiveness were measured. RESULTS: Intelligence and achievement for referred and nonreferred children with NSS were average. Referred children with NSS were reported to have more externalizing behavior problems and poorer social skills than nonreferred children with NSS and children in the control group. Family adaptability and cohesiveness were comparable across groups. CONCLUSIONS: Children with NSS have normal psychosocial function, and results suggest that externalizing behavior problems, attention problems, and poor social skills in children referred to clinics for NSS are inappropriately attributed to short stature.

Normal intelligence with severe insulin-like growth factor I deficiency due to growth hormone receptor deficiency: a controlled study in a genetically homogeneous population.

Superior school performance was reported for 52 Ecuadorian probands with severe deficiency of insulin-like growth factor I (IGF-I) due to GH receptor deficiency (GHRD) resulting from homozygosity for the E180 splice mutation of the GHR. In contrast, subnormal intelligence was reported in a study of 18 genetically heterogeneous Israeli patients, attributed to frequent hypoglycemia or IGF-I dependence of brain development. This study is the first controlled evaluation of the intellectual ability of patients with GHRD. We compared the intelligence of 18 patients of school age (mean +/- SD age, 11.5 +/- 2.8 yr), 42 of their relatives (11.5 +/- 2.8 yr), and 28 community controls (10.0 +/- 0.8 yr), using a battery of intelligence tests that have been validated in cross-cultural research, designed to minimize the effects of physical size, motor coordination, and cultural background. Because all patients had the same GHR mutation, for which the carrier state could be determined, this study also investigated whether heterozygosity for mutation of the GHR among unaffected relatives is associated with intelligence. The intellectual ability of the patients with GHRD was not significantly different from that of their relatives (P > 0.05) on the psychometric tests of intelligence and was comparable to that of the community controls on the chronometric tests. Homozygosity or heterozygosity for the mutation in the GHR gene common to Ecuadorian patients was unrelated to intelligence (P > 0.05). These results indicate that the gene defect causing GHRD is not related to intelligence in the Ecuadorian population. They also indicate that GH-induced IGF-I production is not required for normal brain growth in utero or for postnatal intellectual development.

The construct validity of the Multidimensional Aptitude Battery: a word of caution.

Results of an hierarchical factor analysis with university students (N = 101) do not support the construct validity of the Multidimensional Aptitude Battery (MAB). Although the MAB Full Scale IQ seems to be a valid measure of general mental ability, the construct validity of the Verbal and Performance scale IQs is not supported. Therefore, the Verbal and Performance IQs should be interpreted with caution, if at all. In addition, re-analysis of previous investigations of the MAB underscores the importance of ascertaining the reading level of subjects prior to the administration of the MAB. Marginal reading proficiency, especially on a timed paper-and-pencil test such as the MAB, will confound results.

An exchange assay for the measurement of cell nuclear estrogen receptors in microdissected brain regions.

An exchange assay is described for the measurement of nuclear estrogen receptors (ERn) in microdissected brain regions. The distribution of ERn in the hypothalamus and amygdala of the rat 1 h after an injection of estradiol (E) is presented. Combining the exchange assay with a previously described method for measurement of cytosol estrogen receptors (ERc) in microdissected brain samples, gonadectomized male and female rats were compared for ERc and ERn. While ERc concentrations tended to be higher in females than in males in all regions of the hypothalamus, with a significant sex difference in the arcuate-median eminence, no sex difference in ERn concentrations was observed after E injection. These results suggest that ERc measurements alone are not sufficient to establish the capacity of the E receptor system: ERn measurements are also necessary to establish the relationship between receptor levels and physiologic estrogen responsiveness.

Chlamydia pneumonia in infants: radiography in 125 cases.

Chlamydia trachomatis was recently discovered to be the causative organism in a distinctive afebrile pneumonia occurring in infants under 6 months of age. Experience with the first 125 cases seen at this hospital during a 3 1/2 year period is reported. Chest radiographs were reviewed of 2,273 infants in this age group with signs of lower respiratory tract infection. The first group comprised 148 patients admitted to the hospital. Chlamydia pneumonia was diagnosed in 41 cases. The second group of 2,125 infants was first seen in the outpatient department where 84 additional cases were detected. From this experience it was concluded that, although there are no radiographic findings specific for Chlamydia pneumonia, a combination of the clinical and radiographic findings strongly suggests the diagnosis before cultures and serum antibody titers are available. Important clinical features include age of onset at 2-14 weeks of age, cough, lack of fever, and elevated serum immunoglobulins. Most chest films show bilateral hyperexpansion and diffuse infiltrates with a variety of radiographic patterns including interstitial, reticular nodular, atelectasis, coalescence, and bronchopneumonia. Pleural effusion and lobar consolidation are not seen. The radiographic changes often suggest a more serious illness than that observed clinically. Radiographic features are described in detail.

Carcinoma of the pancreas occuring in a child: a case report with description of gray scale ultrasound findings.

This is a report of the gray scale ultrasound findings of pancreatic carcinoma occurring in a child. Although this tumor is rare, the preoperative diagnosis can be made if the physician is aware of this possibility. 99 mTc sulfur colloid radionuclide scan, liver spleen scan, gallium scan, and ultrasound examinations are helpful in distinguishing the site of origin of upper abdominal masses.

Scintigraphic evaluation of childhood malignancies by 67Ga-citrate.

The utility and limitations of 67Ga scintigraphy in children with solid tumors were evaluated. Thirty-five patients with malignancies (13 lymphoreticular neoplasms, 11 soft-tissue sarcomas, 8 neuroblastomas, and 3 primary bone tumors) had a 67Ga-citrate scan as part of their clinical evaluation. The sensitivity and specificity of the test were analyzed for the different tumor types. The overall sensitivity of the 67Ga-citrate scan for the lymphoma group was 87%. Higher values were obtained for the mediastinal and abdominal regions. Ninety-three per cent of the involved sites were correctly identified by 67Ga scintigraphy in the soft-tissue sarcoma group. Small lung metastases, however, were missed on scan. Thus, 67Ga scans should be complemented with chest radiographs and whole chest tomograms for both initial evaluation and follow-up in those patients. 67Ga had low sensitivity for neuroblastoma.

Acid mucopolysaccharides of chick-embryo cartilage in osteolathyrism.

1. In view of the suggested association between collagen and acid mucopolysaccharides in the connective tissues, this study was designed to see whether the lathyrus factor, beta-aminopropionitrile, affected the acid mucopolysaccharides as well as inhibiting the normal polymerization of collagen. The changing pattern of these two components of cartilage from normal and lathyritic chick embryos aged 14-20 days is described. The chondroitin sulphates and their protein complexes have been isolated from these cartilages, characterized and compared, particularly with respect to their sulphate content; no significant differences in quality or quantity were detectable. 2. Saline extracts of normal and lathyritic cartilages were also compared; whereas the collagen content of lathyritic extracts was increased to ten times that in the normal, the acid mucopolysaccharide content of both extracts was always the same. 3. It therefore appears that in the chick embryo beta-aminopropionitrile does not affect the acid mucopolysaccharides of the developing cartilage.